(2020). "Evidence-based treatments for couples with unexplained infertility: a guideline." Fertility and Sterility 113(2): 305-322.
	Objective: To provide evidence-based recommendations to practicing physicians and others regarding the effectiveness and safety of therapies for unexplained infertility.; Methods: ASRM conducted a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1968 through 2019. The ASRM Practice Committee and a task force of experts used available evidence and informal consensus to develop evidence-based guideline recommendations.; Main Outcome Measure(s): Outcomes of interest included: live-birth rate, clinical pregnancy rate, implantation rate, fertilization rate, multiple pregnancy rate, dose of treatment, rate of ovarian hyperstimulation, abortion rate, and ectopic pregnancy rate.; Result(s): The literature search identified 88 relevant studies to inform the evidence base for this guideline.; Recommendation(s): Evidence-based recommendations were developed for the following treatments for couples with unexplained infertility: natural cycle with intrauterine insemination (IUI); clomiphene citrate with intercourse; aromatase inhibitors with intercourse; gonadotropins with intercourse; clomiphene citrate with IUI; aromatase inhibitors with IUI; combination of clomiphene citrate or letrozole and gonadotropins (low dose and conventional dose) with IUI; low-dose gonadotropins with IUI; conventional-dose gonadotropins with IUI; timing of IUI; and in vitro fertilization and treatment paradigms.; Conclusion(s): The treatment of unexplained infertility is by necessity empiric. For most couples, the best initial therapy is a course (typically 3 or 4 cycles) of ovarian stimulation with oral medications and intrauterine insemination (OS-IUI) followed by in vitro fertilization for those unsuccessful with OS-IUI treatments. (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

(2021). "A Clincal trial to study the effects of two drugs,hinguvadi taila yoni pichu and hinguvadi churna orally in moderate to severe mensstrual pain due to dysmenorrhea."
	INTERVENTION: Intervention1: Hingvadi Taila: Hingvadi Tila Yoni Pichu with 5‐10 ml taila per vaginal given for 7 days prior to menses for three consecutive cycles Control Intervention1: Hinguvadi Churna: Hinguvadi Churna given twice a day orally with lukewarm water 7 days prior to menses for three consecutive cycles CONDITION: Health Condition 1: E348‐ Other specified endocrine disorders PRIMARY OUTCOME: To evaluate the efficacy of hingvadi taila yoni pichu for relief in pain in kasthartavaTimepoint: Relief in pain after 12 week of medication SECONDARY OUTCOME: â?¢To Compare the effect of Hingvadi Taila Yoni Pichu and Hingvadi churna orally for relief in pain in Kasthtartava. ; Timepoint: Relief in pain. INCLUSION CRITERIA: Married Females in age group of 20 to 35 years Patients coming with chief complaint of kashtatrtava with irregular menses. Patients having scanty or average amount of menses along with associated symptoms : ï?? Lower abdominal pain ï?? Low back pain ï?? Nausea and vomiting ï?? Irregular Menses ï?? Diarrhoea Patients with H/O using analgesics and other drugs during menses Patients suffering from dysmenorrhea for more than 3 consecutive cycles.

(2021). "Diagnostics and treatment of provoked vestibulodynia: A Systematic Review." Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU): SBU Systematic Review Summaries.
	The aim was to assess the scientific evidence for methods of diagnosing and treating provoked vestibulodynia through a systematic review. In addition, social and ethical aspects were addressed. (Copyright © 2021 by SBU – Swedish Agency for Health Technology Assessment and Assessment of Social Services.)

(2021). "EFFORT: efficacy of Adavosertib in PARP Resistance: a Randomized 2-Arm Noncomparative Phase 2 Study of Adavosertib With or Without Olaparib in Women With PARP-Resistant Ovarian Cancer." Clinical advances in hematology & oncology 19(8): 14‐15.
	
(2021). "Erratum: efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: subgroup Analysis Findings From the SOLO1 Trial (J Clin Oncol DOI: 10.1200/JCO.20.00799)." Journal of Clinical Oncology 39(12): 1414.
	The October 20, 2020, article by DiSilvestro et al entitled “Effi­cacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial” (J Clin Oncol 10.1200/ JCO.20.00799) was published with errors.

(2021). "Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline." Fertility and Sterility 116(1): 36-47.
	Objective: To provide evidence-based recommendations to practicing physicians and others regarding the efficacy of oocyte cryopreservation (OC) for donor oocyte in vitro fertilization and planned OC.; Methods: The American Society for Reproductive Medicine conducted a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1986 to 2018. The American Society for Reproductive Medicine Practice Committee and a task force of experts used available evidence and through consensus developed evidence-based guideline recommendations.; Main Outcome Measure(s): Outcomes of interest included live birth rate, clinical pregnancy rate, obstetrical and neonatal outcomes, and factors predicting reproductive outcomes.; Result(s): The literature search identified 30 relevant studies to inform the evidence base for this guideline.; Recommendation(s): Evidence-based recommendations were developed for predicting the likelihood of live births after planned OC, autologous OC in infertile women, and donor OC, as well as factors that may impact live birth rates. Recommendations were developed regarding neonatal outcomes after using fresh vs. cryopreserved oocytes in cases of autologous or donor oocytes.; Conclusion(s): There is insufficient evidence to predict live birth rates after planned OC. On the basis of limited data, ongoing and live birth rates appear to be improved for women who undergo planned OC at a younger vs. older age. Although there are no significant differences in per transfer pregnancy rates with cryopreserved vs. fresh donor oocytes, there is insufficient evidence that the live birth rate is the same with vitrified vs. fresh donor oocytes. Neonatal outcomes appear similar with cryopreserved oocytes compared with fresh oocytes. Future studies that compare cumulative live birth rates are needed. (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

(2021). "Expression of Concern: the effects of vitamin D and evening primrose oil co-supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D-deficient women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial." Endocrine research 46(1): 44.
	
(2021). "An open, randomized, controlled clinical trial to evaluate the effects of acupuncture and cupping in the treatment for postmenopausal women with stress urinary incontinence."
	INTERVENTION: Treatment group:Based on PFMT, acupuncture and cupping;Control group:Pelvic floor muscle training; CONDITION: Stress urinary incontinence in postmenopausal women PRIMARY OUTCOME: 1‐hour pad test; SECONDARY OUTCOME: International Consultation on Incontinence Questionnaire‐Short Form;Incontinence quality of life questionnaires;The average number of urinary incontinence within 24 hours;Three‐dimensional ultrasound examination of pelvic floor lesions; INCLUSION CRITERIA: 1. Conform to the diagnostic criteria of SUI in the "Guidelines for the Diagnosis and Treatment of Female Stress Urinary Incontinence (2017)"; 2. More than 12 months since the woman's last menstruation.

(2022). "Combination Vistusertib and Anastrozole Shows Benefit in Endometrial Cancer." Cancer discovery 12(7): OF20.
	The primary endpoint of 8-week progression-free rate was met with this combination. (©2022 American Association for Cancer Research.)

(2022). "Mirvetuximab soravtansine (Elahere) for ovarian, fallopian tube, and primary peritoneal cancer." The Medical letter on drugs and therapeutics 64(1665): e205-e206.
	
(2022). "Oteseconazole (Vivjoa) for recurrent vulvovaginal candidiasis." The Medical letter on drugs and therapeutics 64(1656): 124-126.
	
(2022). "Same-Day Compared With Overnight Cervical Preparation Before Dilation and Evacuation Between 16 and 19 6/7 Weeks of Gestation: a Randomized Controlled Trial: correction." Obstetrics and Gynecology 140(2): 344‐345.
	
(2023). "Additive effects of yoga in women with polycystic ovary syndrome (PCOS) with infertility." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/02/049824.
	INTERVENTION: Intervention1: Yoga therapy: All the patients allocated in intervention group will be subjected to YOGA for 6 weeks before starting ovulation induction treatment (table 1) and will continue throughout the treatment duration. Control Intervention1: no yoga: Patients will be directly started on ovulation induction cycles. A maximum of 4 cycles of OVI will given to every patient CONDITION: Health Condition 1: E282‐ Polycystic ovarian syndrome PRIMARY OUTCOME: Follicular response (dominant follicle â?¥17mm) among women getting yoga therapy in addition to ; ovulation induction cycles among infertile PCOS womenTimepoint: Follicular response (dominant follicle â?¥17mm) among women getting yoga therapy in addition to ; ovulation induction cycles among infertile PCOS women at baseline, 6 weeks and 12 weeks. SECONDARY OUTCOME: Clinical parameters ( BMI, waist circumference (WC),waist hip ratio (WHR), neck circumference ; (NC) ; â?¢ Metabolic parameters ( HOMA‐IR, Lipid profile) ; â?¢ Endocrine parameters (LH/FSH ratio, AMH, SHBG, testosterone)Timepoint: AT baseline; 3 months and 6 months Duration of stimulation to achieve target follicular response ; â?¢ Clinical pregnancy rate (documented viable pregnancy on USG) ; â?¢ Ongoing pregnancy rate ; â?¢ Live birth rateTimepoint: During ovulation induction cycles monitoring To evaluate the effect of yoga on following parameters: ; â?¢ Need to add gonadotrophins to ovarian stimulation ; â?¢Timepoint: during ovulation induction cycles INCLUSION CRITERIA: Infertile PCOS women diagnosed according to modified Rotterdam criteria will be recruited for the study.

(2023). "Adjuvant Treatment In HPV-DNA Positive Patients: a Plasma Biomarker For Chemotherapy In Locally Advanced Cervical Cancer." https://clinicaltrials.gov/show/NCT05764044.
	A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA‐HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. Patients will be randomized by stratified randomization process to belong to one of the groups: control (Group B) or intervention (Group C), emphasizing homogeneity of risk factors between them. A randomized list will be generated by using a suitable software, using variable size blocks (2 or 4), with stratification for site and staging. The confidentiality of the randomization list will be maintained through an automated, centralized, Internet‐based randomization system, available 24 hours a day (RedCap). Selected patients must receive standard treatment based on concomitant chemoradiotherapy regime, with dose of RT of 40‐50Gy (considering additional boost of 10‐15Gy in lymph nodes, radiologically or surgically, compromised) and brachytherapy of 30‐40Gy and cisplatin 40mg/m2 weekly. After four weeks of the end of treatment, a qualitative and quantitative research of HPV DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 HPV DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MR) of abdomen and pelvis and clinical and gynecological examination at every four months.

(2023). "Approval." Brown University Psychopharmacology Update 34(12): 8-8.
	The article focuses on the FDA's approval of zuranolone, an oral medication marketed by Sage Therapeutics, for the treatment of postpartum depression, based on successful results from two clinical trials that demonstrated its effectiveness in improving depressive symptoms compared to a placebo.

(2023). "autologous platelet rich plasma for Ovarian rejuvenation."
	INTERVENTION: Intervention1: Intraovarian injection of autologous Platelet rich plasma.: Autologous Platelet rich plasma intra ovarian injection will be given between day 7 and day 9 of periods for three consecutive cycles (cycle 1,2 and 3) in addition to Dehydroepiandrosterone (DHEA)(75 mg per day) Control Intervention1: Dehydroepiandrosterone (DHEA)(75 mg per day): Dehydroepiandrosterone (DHEA)(75 mg per day)will be administered for 3 cycles CONDITION: Health Condition 1: N978‐ Female infertility of other origin PRIMARY OUTCOME: 1.Antral Follicle Count (defined as all follicles of 2‐9 mm on day 2 scan on TVS), ; 2.Serum AMH ; 3.Serum FSH at the end of the treatment cycle. ; Timepoint: 3 months SECONDARY OUTCOME: conception rateTimepoint: after 3 months INCLUSION CRITERIA: Serum AMH (Anti Mullerian Hormone)<=1.2/ml, AFC (Antral Follicle Count) < 5(Follicles between 2‐9 mm assessed sonographically on day 2/3 of periods), Serum FSH(Follicle Stimulating Hormone) > 12, Hb >11 gm% and platelets >1.5 lakhs.

(2023). "Cabergoline: an Effective Intervention for Unwanted Lactation After Second Trimester Uterine Evacuation." OB/GYN clinical alert 40(4): 1‐8.
	
(2023). "Cannabidiol for the Treatment of Pelvic Pain in Endometriosis (DREAMLAND)."
	The Dreamland study is a two‐arm, parallel‐group, individually randomized (1:1 allocation ratio), controlled by disease stage, participant and investigator blinded, single‐site superiority trial of oral cannabis extract (CBD). CBD will be given orally starting at 10 mg daily and up‐titrated to a maximum dose of 150 mg daily. Dose up‐titration will be based on clinical response or side effects, whichever comes first. After 63 days of treatment, gradual withdrawal will be performed during one week. Then, at 70 days, there will be an open‐label extension wherein all participants from control group will be offered a course of CBD according to the same previous protocol. This research intends to : 1. Assess whether the daily use of CBD, for nine weeks, will reduce the pain level of these women. 2. Assess whether the daily use of CBD, for nine weeks, will modify pain threshold. 3. Assess whether the daily use of CBD, for nine weeks, will interfere in psychological symptoms. 4. Assess the possible adverse effects of using CBD

(2023). "CIRCUIT TRAINING EXERCISE EFFECT ON INFLAMMATORY MARKER AND INSULIN RESISTANCE ON POLYCYSTIC OVARIAN SYNDROME."
	INTERVENTION: Intervention1: CIRCUIT TRAINING: The intervention is circuit training with diet modification and physical activity recommendation.The exercise sessions are through group therapy,with direct session containing 10‐15 participatant per group .Exercise duration is one hour a day consist of 10 minutes of warm up, 40 minutes of training sessions ,10 minutes of cool down. 40 minutes of training session is divided into circuit consisting of 10 exercises (5 aerobic and 5 body weight resisted exercises).The exercises include push ups, squats, crunches, lunges, superman exercises, light jumping, running on spot, foot stamping, steps, jumping jacks. Each exercise will be done at 50‐60% of HRma Xinitially for 1‐8 weeks and 60‐70% of HRma Xduring the 9‐12 weeks of treatment peroid. Each exercises in the circuit will be provided for 30 seconds with rest peroid of 20 seconds in between.The rest period between each set is 3 minutes.Total study duration is 12 weeks, and participants of the intervention group will receive exercises session 3 days a week Control Intervention1: PHYSICAL ACTIVITY RECOMMENDATION: As per WHO 2020 recommendation ,it is strongly recommended that adults 18‐64 years, should take up regular physical activity. Adults should do atleast 150‐300 minutes of moderate intensity physical activity or an equivalent combination of moderate and vigorous intensity activity throughout the week, for substantial health benefits ,Participants will be advised to do muscle strengthening activities at moderate or greater intensity for additional health benefits. Limit the time of sedentary behavior and replace it with physical activity Control Intervention2: PHYSICAL ACTIVITY RECOMMENDATION: As per WHO 2020 recommendation ,it is strongly recommended that adults 18‐64 years, should tak CONDITION: PRIMARY OUTCOME: INSULIN RESISTANCE‐HOMAIRHIGH SENSITIVE C REACTIVE PROTIENTimepoint: BASELINE ; 12 WEEKS SECONDARY OUTCOME: ANTHROPOMETRIC MEASURESTimepoint: BASELINE WEIGHT, ; 12WEEKS INCLUSION CRITERIA: College going females of 18‐24 years of age Diagnosed case of PCOS Nulliparous women

(2023). "Clinical observation on the prevention and treatment of radioactive vaginal injury by clearing heat, detoxifying and generating muscle formula." https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300068023.
	INTERVENTION: Test group:Clearing heat, detoxifying and muscle building formula vaginal douche;Control group:Vaginal douching with potassium permanganate 1:5000; CONDITION: Radiation vaginal injury PRIMARY OUTCOME: To observe the incidence and extent of radiation vaginal injury; SECONDARY OUTCOME: Determination of the efficacy of Chinese medical evidence;Routine examination of vaginal secretions;Quality of life questionnaire;Routine urine test;Vaginal ultrasound; INCLUSION CRITERIA: ? All cervical cancer cases had a pathological diagnosis. ?Cervical cancer patients with stage II B to III A according to the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging of cervical cancer requiring vaginal brachytherapy; ?Females aged 18 to 70 years; ?Strength status (KPS) score > 70 points; ? Voluntary participation in informed consent.

(2023). "Clinical study of modified letrozole regimen in ovulation induction in patients with polycystic ovary syndrome." https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300071007.
	INTERVENTION: Experimental group:Letrozole;Control group:Letrozole; CONDITION: polycystic ovary syndrome PRIMARY OUTCOME: Dominant follicle rate(First period);Ovulation rate after trigger(First period); SECONDARY OUTCOME: Expulsion cycle cancellation rate(First period);ovulation rate(First period);clinical pregnancy rate(First period);Biochemical pregnancy rate(First period);Early/late abortion rate(First period);Multiple pregnancy rate(First period);OHSS rate(First period);Intimal thickness(First period);Intimal morphology(First period);LUFS rate(First period);Malformation rate(First period);Cumulative dominance number of follicles;Cumulative ovulation rate;Cumulative biochemical pregnancy rate;Cumulative clinical pregnancy rate;Cumulative early/late abortion rate;Cumulative live birth rate;Cumulative multiple pregnancy rate;Cumulative OHSS rate;Cumulative LUFS rate;Live birth rate(First period); INCLUSION CRITERIA: 1.PCOS and infertility were diagnosed PCOS is diagnosed according to Rotterdam consensus as fulfilling at least two of the three criteria: (1) oligo‐anovulation or anovulation; (2) clinical or biochemical signs of hyperandrogenism; and (3) polycystic ovarian morphology on ultrasound, as defined by at least one ovary with 12 follicles or volume 10 ml. 2.Infertility due to PCOS,amenorrhea and ovulation disorder,at least one of the fallopian tubes is unobstructed,there are indications of out‐patient expulsion promotion,and no contraindication of expulsion promotion (1)To induce ovulation to guide cohabitants (2)intrauterine artificial insemination with ovulation induction 3.PCOS intended to receive CET(IVF/ICSI/PGT)for endometrial preparation with LE stimulation due to irregular menstruation and ovulation disorder 4.=38 years of age at oocyte retrieval; 5.She has not used LE/CC and other efflu Xstimulating drugs in the last 3 mon

(2023). "The clinical study on pulse acupuncture for treating TP/TC chemotherapy-induced alopecia of patients with gynecologic cancers."
	INTERVENTION: Group 1:routine acupuncture;Group 2:pulse acupuncture;Group 3:comprehensive nursing intervention; CONDITION: chemotherapy‐induced alopecia PRIMARY OUTCOME: Grading of toxic effects on the severity of hair loss in World Health Organisation (WHO)Handbook for reporting results of cancer treatment; SECONDARY OUTCOME: Hair growth rate;Condition of hair growth ;Karnofsky Performance Status (KPS) Scale;Chemotherapy‐induced Alopecia Distress Scale (CADS);quality of life index; INCLUSION CRITERIA: 1. Gynecological malignant tumors diagnosed by clinicopathology, including ovarian cancer, endometrial cancer, and cervical cancer; 2. Receive postoperative adjuvant chemotherapy or palliative chemotherapy for the first time; 3. Completed all TP (paclitaxel + cisplatin) or TC (paclitaxel + carboplatin) chemotherapy courses (4‐8 courses); 4. According to Dean's Hair Loss Scale, subjectively evaluate the degree of hair loss >= 2 grades; 5. No medical history related to obvious hair loss; 6. The general condition is good, and the Karnofsky score is greater than or equal to 60 points; 7. The expected survival period is more than 3 months; 8. Female patients aged between 18 and 70 years; 9. Patients who agree to participate in this study and sign the informed consent form.

(2023). "Clinical study on the efficacy and safety of remazolam besylate for induction and maintenance of general anesthesia in gynecological laparoscopic surgery." https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300068042.
	INTERVENTION: Experimental group:Remazolam sedation;Control group:Propofol sedation; CONDITION: Gynecological uterine and adnexal diseases PRIMARY OUTCOME: Incidence of intraoperative hypotension; SECONDARY OUTCOME: Vital signs;Anesthesia wake time;Adverse reactions; INCLUSION CRITERIA: 1. Patients undergoing gynecological laparoscopic general anesthesia surgery (except for patients with malignant tumors); 2. Age 18‐60 years; 3 Body mass inde X(BMI): 18.5‐30 kg/m^2; 4 American Society of Anesthesiologists Grading (ASA) Grades I‐III; 5. Subjects voluntarily participate in the trial and sign the informed consent form of the trial.

(2023). "Clotrimazole treatment in vaginal Infections." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/02/049628.
	INTERVENTION: Intervention1: Candimilt® 500 vaginal capsules: Single STAT dose 500 mg vaginally on day 1 alone Control Intervention1: Canesten® vaginal tablets: Single STAT dose 500 mg vaginally on day 1 alone. CONDITION: Health Condition 1: B373‐ Candidiasis of vulva and vagina PRIMARY OUTCOME: 1.Number of patients showing resolution of clinical signs suggestive of infective vaginitis and a vaginal swab that is negative for candidal vaginitis ; 2.Clinical response ; 3.Improvement or Resolution of Local signs of inflammation. ; 4.A vulvovaginal symptoms questionnaire (VSQ) will be done at baseline and end of the studyTimepoint: Baseline, day 7 and day 14 SECONDARY OUTCOME: 1.Changes from base line to 4 weeks in Quality of life‐ Questionnaires (Short Form Health‐12). ; 2.Photographic assessments of improvement and tablet dissolution status ‐ will be done for patients who consent for the same. ; LABORATORY STUDIES ; 3.Microbiological cure ‐ evaluation: microscopy of vaginal discharge smears will be done on Baseline and on day 7 and 14 (culture method) ; Timepoint: Baseline, day 7 and day 14 INCLUSION CRITERIA: 1. Women with the symptoms of vulvovaginal candidiasis (based on symptoms and signs after speculum examination); 2. Age at least 18 years; 3. Capable of giving written informed consent; 4. Agree to no intercourse for 8 days from the day of beginning of treatment; 5. Agree not to douche or use any intra‐vaginal products during the study period (including tampons, medications and devices); 6. Non‐pregnant Female patients aged 18 years or more and clinically diagnosed with vulvovaginal candidiasis were included; 7. Capable of giving written informed consent and willing to follow the investigational study procedures and report AEs. 8. Subjects must not be on their menstrual period on the day of screening and do not anticipate their period to begin during treatment (3 days); 9. Subjects must be using an acceptable method of birth control, willing to refrain from sexual intercourse from the da

(2023). "Comparative study between castor oil EMULGEL with clotrimazole vaginal tablet in the treatment of subjects with vulvo-vaginal candidiasis." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/04/051978.
	INTERVENTION: CONDITION: Health Condition 1: N760‐ Acute vaginitis PRIMARY OUTCOME: Clinical cure rate (proportion of participants achieving clinical cure)Timepoint: At baseline, Day‐4 for Clotrimazole 200mg & Day 6 for Castor oil EMULGEL SECONDARY OUTCOME: 1. Microbiological cure rate (Direct microscopy/wet smear): Number of positive findings in direct microscopy in comparison to first visit. ; 2. Therapeutic cure rate: Clinical and microbiological cure combined. ; 3. Total Severity Score (TSS): Individual clinical signs and symptoms. ; 4. Vaginal pH: Mean vaginal pH in comparison to first visit. ; ; ; 5. Patients satisfaction: Patient will be asked how satisfied she was with the treatment received based on 8 standardized questions. ; Timepoint: Castor oil EMULGEL‐ Day‐0 First visit‐ Day‐6 end of treatment. ; Clotrimazole 200mg ‐ Day‐0 First visit‐ Day‐4 end of treatment. INCLUSION CRITERIA: 1. Female patients in reproductive age group (18‐45 years). 2. Patients willing to give written informed consent. 3. Patients with clinical signs and symptoms of vulvovaginal candidiasis (complaints of vaginal pruritus, burning sensation, vulvar soreness or thick curdy discharge).

(2023). "Comparing the effect of nettle extract with COCs on the improvement of clinical and paraclinical symptoms of polycystic ovary syndrome." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20110606006709N25.
	INTERVENTION: Intervention 1: Nettle extract capsules (containing flavonoids, tannins and sterols) in the number of 30 capsules, one daily for three cycles, which will be prepared and packaged by Sina Navandish Company. Intervention 2: Control group: LD capsules (containing 30 micrograms of ethinyl estradiol and 150 micrograms of levonorgestrel), in the number of 21 capsules along with 9 capsules containing an ineffective substance to be consumed in a cycle of 30 capsules per day for three cycles, which will be prepared and packaged by Sina Navandish Company . CONDITION: Clinical and paraclinical symptoms of polycystic ovary syndrome. ; Polycystic ovarian syndrome E28.2 PRIMARY OUTCOME: Average score of hirsutism. Timepoint: Before the intervention and 3 months after the intervention. Method of measurement: Ferriman–Gallwey scale. Serum levels of DHEA and total testosterone. Timepoint: Before the start of the intervention and 3 months after the intervention. Method of measurement: By ELISA method in the central laboratory. SECONDARY OUTCOME: Normalization of menstrual cycles. Timepoint: Before the intervention, one month, two months, and three months after the intervention. Method of measurement: Questionnaire made by the researcher and Higham's chart. Serum level of fasting blood sugar. Timepoint: Before the start of the intervention and and 3 months after the intervention. Method of measurement: By spectrophotometric method in the central laboratory. Serum levels of gonadotropins (FSH and LH). Timepoint: Before the start of the intervention and and 3 months after the intervention. Method of measurement: By ELISA method in the central laboratory. INCLUSION CRITERIA: Confirming the diagnosis of PCOS according to the Rotterdam criteria (clinical or biochemical hyperandrogenism, menstrual cycle disorders or polycystic ovary ultrasound signs) Age 18 to 40 years Being literate in reading and writing BMI between 18.5 and 30 Not using hormonal contraceptives or any other type of hormonal medication currently and during the last three months Not wanting to get pregnant

(2023). "Comparing the effects of biofeedback and brain stimulation treatments on pelvic floor muscle function in women with urinary incontinence." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20230305057630N1.
	INTERVENTION: Intervention 1: Control group: This group receives only routine exercises to strengthen the pelvic floor muscles, each session is 30 minutes and is divided into three parts: 1) Sustained contractions: Patients complete pelvic muscle contraction for 6‐10 seconds each time, then start the next contraction after 10 seconds rest, 8‐10 repetitions per set, 1‐2 sets per session. 2)Phasic contractions: Patients complete pelvic muscle contraction for 2‐5 seconds each time, then rest, rest time is twice the contraction time, 10 repetitions per set, 1‐3 sets per session. 3) Guided training: Patients are asked to simulate activities such as coughing, sneezing while contracting the pelvic floor muscles. Treatment sessions will be held in 3 sessions per week for a total period of 3 weeks. Intervention 2: First intervention group: Pelvic floor muscle strengthening exercises with biofeedback : The treatment program includes 9 sessions of combined pelvic floor rehabilitation, that is, the combination of electromyographic biofeedback and progressive exercises of the pelvic floor muscles, will be used as a therapeutic exercise program. Biofeedback takes 15 minutes. A special vaginal probe of Leukoplast combination, which is the same for all patients, will be used for electromyographic biofeedback applications. Each probe will be unique to the patient. The patient will be given the necessary training to train the pelvic floor muscles alone and using vaginal cones in treatment sessions. According to the Kegel treatment protocol, 300 contractions are performed daily. Contraction of the pelvic floor by maintaining the vaginal cone while standing, lying down, sitting and going up and down the stairs as well as running will be done gradually at home with daily progress. Each patient's in‐per CONDITION: N39.3 Urinary incontinence. ; Stress incontinence (female) (male) PRIMARY OUTCOME: Evaluation of urinary incontinence and vaginal symptoms. Timepoint: Before and after the intervention and one month after the last treatment session. Method of measurement: International Consultation on Incontinence Questionnaire Vaginal Symptoms Module questionnaire. The volume of urine loss. Timepoint: Before and after the intervention and one month after the last treatment session. Method of measurement: One hour pad test. SECONDARY OUTCOME: Bladder displacement amount. Timepoint: Before and after the intervention and one month after the last treatment session. Method of measurement: Ultrasonography. Strength and endurance of pelvic floor muscles. Timepoint: Before and after the intervention and one month after the last treatment session. Method of measurement: Biofeedback. Strength and endurance of pelvic floor muscles. Timepoint: Before and after the intervention and one month after the last treatment session. Method of measurement: Manual assessment with the Oxford scale. Strength and endurance of pelvic floor muscles. Timepoint: Before and after the intervention and one month after the last treatment session. Method of measurement: Perineometer. INCLUSION CRITERIA: Women aged 35 to 70 years with urinary incontinence as the main clinical complaint, without urgent symptoms Urine loss of more than 1 gram per hour should be confirmed by a one‐hour test pad The simultaneous presence of sexual disorders and impotence with urinary incontinence Absence of chronic degenerative diseases that affect muscle and nerve tissues Absence of any degree of pelvic organ prolapse (POP) Absence of active or recurrent urinary tract infections (UTIs) Absence of vulvovaginitis Absence of atrophic vaginitis Absence of copper IUD in the uterus Absence of pregnancy or childbirth less than 6 months Not suffering from diabetes, neurological disease, mental illness, and debilitating chronic diseases such as kidney failure and heart pacemakers. Absence of taking drugs that affect urination No history of surgical or drug treatment of SUI No history of abdominal and inguinal hernia No history of any surgery in the abdo

(2023). "Comparing the Effects of Mycozin and Clotrimazole on Vaginal Candidiasis." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20120718010324N77.
	INTERVENTION: Intervention 1: Intervention group 1 will use Mycozin vaginal cream at bedtime for one week. Intervention 2: Intervention group 2 will use Clotrimazole 1% vaginal cream at bedtime for one week. CONDITION: B37.3 Vaginal Candidiasis. ; Candidiasis of vulva and vagina PRIMARY OUTCOME: Frequency of clinical symptoms (smell, quantity, consistency, color and appearance of vaginal secretions, vaginal inflammation, appearance of cervix). Timepoint: Before the intervention and 10 to 15 days after the intervention. Method of measurement: Clinical examination by the researcher and clinical symptoms checklist. Frequency of laboratory symptoms (negative smear and culture of vaginal secretions). Timepoint: Before the intervention and 10 to 15 days after the intervention. Method of measurement: Sampling will be done with a sterile cotton swab from the posterior fornix of the vagina, and we will dip the swab inside the blood culture tubes and gently shake it inside the solution until the sample dissolves in it. Incubation will be at 37 degrees for 2 to 4 hours, and a drop of the contents of the tube solution will be transferred on a slide. We examine the slide under the microscope with high and low magnification. Germ tube formation test is a quick test to identify Candida albicans and differentiate it from other yeasts. Frequency of patient complaints (secretions, dysuria, frequency, itching, itching during intercourse, pain in the lower abdomen, burning sensation during intercourse, and dyspareunia). Timepoint: Before the intervention and 10 to 15 days after the intervention. Method of measurement: Stated by the participants and complaints checklist. SECONDARY OUTCOME: PH of vaginal secretions. Timepoint: Before the intervention and 10 to 15 days after the intervention. Method of measurement: PH paper. Satisfaction with the treatment. Timepoint: 10 to 15 days after the intervention. Method of measurement: Satisfaction questionnaire. Side events. Timepoint: 10 to 15 days after the intervention. Method of measurement: Side events checklist. INCLUSION CRITERIA: Age 18‐45 years married Being literate in reading and writing Lack of allergy to herbal medicines Suffering from candidal vaginitis

(2023). "Comparision of the effect of vitamin D3 and probiotic containing lactic acid bacteria co-supplementation with vitamin D3 on serum 25(OH)D levels in patients with polycystic ovary syndrome." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20221121056563N1.
	INTERVENTION: Intervention 1: Intervention group1: Probiotic group ‐ Vitamin D 50,000 IU vitamin D3 every two weeks along with one capsule of Lactofem containing Lactobacillus rhamnosus, Lactobacillus fermentum, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus gasseri and Lactobacillus bulgaricus in the amount of 109 CFU along with fructo‐oligosaccharides as prebiotics. They will receive the prebiotic daily. Intervention 2: Intervention group 2:In the vitamin D group, they will receive 50,000 IU of vitamin D3 every 2 weeks. CONDITION: Condition 1: Polycystic ovarian syndrome. Condition 2: Vitamin D deficiency, unspecified. ; Polycystic ovarian syndrome ; Vitamin D deficiency, unspecified E28.2 E55.9 PRIMARY OUTCOME: Serum level of 25 hydroxyvitamin D. Timepoint: The beginning and end of the study. Method of measurement: blood sample. SECONDARY OUTCOME: Body composition. Timepoint: The beginning and end of the study. Method of measurement: Bioelectrical Impedance Analysis. Body Mass Index. Timepoint: The beginning and end of the study. Method of measurement: Bioelectrical Impedance Analysis. Weight. Timepoint: The beginning and end of the study. Method of measurement: Scale. INCLUSION CRITERIA: Age range 18‐40 years A resident of Urmia Diagnosis of PCOS based on the Rotterdam indices. The Rotterdam criteria include having more than two of these symptoms: oligo/no ovulation, hyperandrogenism (symptoms such as hirsutism, acne, male pattern alopecia, increased free testosterone) and polycystic ovaries based on ultrasound (having 12 or more The follicle in each ovary is 2‐9 mm in size People with blood levels of 25 hydroxyvitamin D less than 30 ng/ml

(2023). "Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer." https://clinicaltrials.gov/show/NCT05712941.
	This is a randomized, double‐blinded, placebo‐controlled Phase 3 clinical trial to compare the combination of lerociclib (administered at 150 mg twice a day (BID) with letrozole (administered at 2.5 mg once a day (QD) to that of placebo with letrozole (2.5 mg QD) in female participants with Grade 1 or Grade 2 (ie, low‐grade histology) endometrioid endometrial cancer (EC) and advanced/metastatic or recurrent disease. The study population will consist of female participants with endometrioid EC who are treatment‐naïve in the advanced/metastatic setting (ie, the first‐line [1L] population). Participants may have received prior adjuvant chemotherapy/chemoradiation for localized disease if the adjuvant therapy was administered ≥ 6 months prior. All participants must also be naïve to prior endocrine therapy for EC, and confirmed as medically postmenopausal to be eligible. The study will comprise a Screening Period of up to 28 days in duration; a Study Treatment Phase; a Safety Follow‐up Period spanning the time of study treatment discontinuation‐including discontinuation due to confirmed disease progression, as applicable‐through 28 days after the participant's last dose of any study intervention or the start of subsequent anticancer therapy (whichever occurs first); and a Survival Follow‐up Period that will continue until the participant's death or until at least 50% of all study participants have died (whichever occurs first). While receiving their randomized assigned study treatment, participants will undergo imaging assessments via computed tomography (CT) of the chest/abdomen/pelvis with contrast‐ or, if CT is medically contraindicated (eg, due to iodine allergy), via magnetic resonance imaging (MRI) with gadolinium‐every 8 weeks for the first 12 months and then every 12 weeks thereafter.

(2023). "Comparison of the effect of Agnugol, Cimifugol , Soyagol , vitagnus and EsCitalopram." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20080902001181N4.
	INTERVENTION: Intervention 1: first intervention group: One CimiFugol coated tablet containing 6.5 mg of dry root of black cohosh plant manufactured by GolDaru Company will be taken daily for 8 weeks every night at a certain time with some water, preferably before going to bed. Intervention 2: second intervention group: One Agnugol coated tablet daily containing 4.8 mg of dry extract of the fruit of Vite Xagnus‐castus plant (standardized as 0.42‐0.58 mg of Ecobin) manufactured by GolDaru Company for 8 weeks every night at a certain time with some water preferably before going to bed. Intervention 3: The third intervention group: once a day before meals, Vitagnus coated tablets containing Vite Xagnus‐castus plant (standardized as 1.2‐3.3 mg of Ecobin) manufactured by Porsina Company will be consumed for 8 weeks. Intervention 4: 4th intervention group: They take one Soyagol coated tablet containing 50 mg of soy isoflavone, manufactured by GolDaru Company, for 8 weeks every night at a certain time with some water after meals. Intervention 5: The fifth intervention group: take one 10 mg Escitalopram tablet daily after lunch for 8 weeks. CONDITION: Menopause. ; Menopausal and female climacteric states N95.1 PRIMARY OUTCOME: Total score of menopausal symptoms. Timepoint: The total score of menopausal symptoms is checked at the beginning of the study (before the start of the intervention), the fourth and the eighth week after the start of the intervention. Method of measurement: Menopause Rating Scale (MRS). INCLUSION CRITERIA: Obtaining a score of 5 and above from the MRS questionnaire 12 months or more have passed since menopause Age between 45 and 65 years

(2023). "Comparison of the effect of Cabergoline versus Dienogest on markers in endometriosis." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/04/051886.
	INTERVENTION: Intervention1: Cabergoline: 0.5mg twice weekly for 6 months Control Intervention1: Dienogest: 2mg OD for 6 months CONDITION: Health Condition 1: N801‐ Endometriosis of ovary PRIMARY OUTCOME: Change in the serum levels of pro inflammatory levels post treatment ; 1.Serum Vascular endothelial growth factor level ; 2.Serum Tumor necrosis factor alpha level ; 3.Serum high sensitivity C Reactive protein ; Timepoint: 0,6,9 months SECONDARY OUTCOME: To compare the efficacy of cabergoline with dienogest on ; 1.Reduction in post treatment pain by VAS ; 2.Reduction in post treatment volume measured on USG ; 3.Pain scoring by VAS after 3 months of stopping drug ; Timepoint: 0,3,6,9 months INCLUSION CRITERIA: Women with diagnosis of endometriosis on laparoscopy or ultrasound.

(2023). "Comparison of the Effect of Period Patch Analgesia with Mefenamic Acid in Primary Dysmenorrhea." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20230112057117N1.
	INTERVENTION: Intervention 1: Administration of mefenamic acid, initial dose of two 250 mg capsules, then 250 mg capsule every si Xhours until pain control , maximum up to 48 hours. Intervention 2: Sticking the menstrual patch(Razan Pharmed) on the skin of the suprapubic area and changing it every eight hours to control the pain , maximum up to 48 hours. CONDITION: Condition 1: Primary Dysmenorrhea. Condition 2: Primary Dysmenorrhea. ; Primary dysmenorrhea ; Primary dysmenorrhea N94.4 PRIMARY OUTCOME: Primary Dysmenorrhea. Timepoint: Comparison of the analgesic effect of mefenamic acid and menstrual patch when used during a menstrual cycle. Method of measurement: Based on Numerical analogue pain score. INCLUSION CRITERIA: Nulipariety 18‐30 years old Regular mensturation BMI<30 Moderate dysmenorrhea atleast for one day Non OCP or IUD user Normal pelvic Exam and pelvic sonography No allergy to mefenamic acid and period patch

(2023). "Comparison of two different vaginal preparations of progesterone for prevention of recurrent preterm birth: a Randomized Controlled Trial."
	INTERVENTION: Intervention1: 200 milligrams of micronized progesterone effervescent vaginal tablet: The effervescent vaginal tablet, contains progesterone in a base of sodium bicarbonate, and an acid‐base reaction occurs when the tablet comes into contact with vaginal moisture, thus releasing carbon dioxide, which improves drug absorption across epithelium. As a result, this formulation has rapid dissolution and quick progesterone absorption. It will be given daily, per vaginally, from (16‐20 weeks Period of Gestation) till delivery Control Intervention1: 200 milligram of micronized progesterone gelatin capsule, vaginally: With repeated administration, the vaginal gel will build up in the vagina and will release progesterone gradually. It will be given daily, per vaginally, from (16‐20 weeks Period of Gestation) till delivery CONDITION: Health Condition 1: O092‐ Supervision of pregnancy with other poor reproductive or obstetric history PRIMARY OUTCOME: To compare micronized progesterone effervescent vaginal tablet with micronized progesterone gelatin capsule used vaginally, for prevention of PTB less than 37 weeks, in women with a prior spontaneous PTB or a mid‐trimester abortion.Timepoint: Till the delivery SECONDARY OUTCOME: 1 To compare the incidence of PTB less than and equal to 32 weeks (very PTB) and less than and equal to 28 weeks (extreme PTB) in the above two groups ; Timepoint: Preterm delivery less than and equal to 32 weeks and 28 weeks respectively To compare the acceptability and tolerability of the two progesterone formulations ; Timepoint: At least 15 days after using the progesterone formulations and later whenever the women complain INCLUSION CRITERIA: 1. Singleton live pregnancy between 16 to 20 weeks. 2. At least one spontaneous mid‐trimester abortion or preterm birth (â?¥16 weeks PoG to <37 weeks PoG) of a singleton infant due to spontaneous Preterm labor or Preterm premature rupture of membranes.

(2023). "Comparison of two doses of urinary human chorionic gonadotropin as trigger on ovulation induction in IUI cycles." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/04/052137.
	INTERVENTION: Intervention1: 5000IU of urinary Human Chorionic Gonadotropin Intramuscular injection as trigger: 5000IU of urinary Human Chorionic Gonadotropin injection intramuscular injection as trigger, single dose when dominant follicle size â?¥18mm in intrauterine insemination cycles Control Intervention1: 10000 IU urinary Human Chorionic Gonadotropin Intramuscular injection as trigger: 10000 IU of urinary Human Chorionic Gonadotropin injection intramuscular injection as trigger, single dose when dominant follicle size â?¥18mm in intrauterine insemination cycles CONDITION: Health Condition 1: N979‐ Female infertility, unspecified PRIMARY OUTCOME: occurrence of ovulationTimepoint: 18 months SECONDARY OUTCOME: 1 Serum β hCG value after 12 hrs of trigger ; 2 Need of second trigger ; 3 Total pregnancy rate ; 4 Clinical pregnancy rate ; Timepoint: 18 months INCLUSION CRITERIA: women with patency of at least one Fallopian tube and her husband having more than 10 million sperms after sperm preparation

(2023). "comparison of two drugs for anaesthesia during dilation and curettage in females with abnormal menstrual bleeding."
	INTERVENTION: Intervention1: inj. Ketamine and Dexmedetomidine: Ketamine 1 mg/kg and Dexmedetomidine 0.5 mcg/kg combined in single syringe given IV slow over 2 min Intervention2: inj propofol and ketamine: inj propofol 1 mg/kg and ketamine 1 mg/kg given IV over 2 min Control Intervention1: inj. Ketamine and Dexmedetomidine: inj. Ketamine 1 mg/kg and Dexmedetomidine 0.5 mcg/kg given IV slow over 2 min Control Intervention2: inj ketamine and propofol: inj propofol 1 mg/kg and ketamine 1 mg/kg given IV over 2 min CONDITION: Health Condition 1: N925‐ Other specified irregular menstruation PRIMARY OUTCOME: Time to onset of sedation (Ramsay sedation score RSS 6) and recovery from sedation (RSS 3)Timepoint: Time to onset of sedation (Ramsay sedation score RSS 6) and recovery from sedation (RSS 3) SECONDARY OUTCOME: 1.Intraoperative Haemodynamics (Heart Rate, Blood Pressure, Spo2, Respiratory rate) ; 2.Post op recovery score ( Modified Aldrete Score) ; 3.Duration of analgesia ; Timepoint: 0min, 10, 20, 30 min INCLUSION CRITERIA: Patients of abnormal uterine bleeding scheduled for elective endometrial sampling American Society of Anaesthesiology I and II

(2023). "Deferred Embryo Transfer in an In Vitro Program With Single Embryo Transfer Policy." https://clinicaltrials.gov/show/NCT05721495.
	The study has been designed as a prospective, randomized, two‐arm, parallel, unblinded study, during which the investigators will include 138 couples (69 in each group) of IVF / ICSI users. Cycles canceled or punctured but without embryo transfer (either due to not obtaining oocytes, non‐fertilization or arrest of embryonic development) will not be included in the study. The assignment of the couples to each of the groups will be carried out by means of a consecutive random sampling procedure. The randomization list will be created specifically for this project and will be kept safely by someone not included in the research team: ‐ Group I (experimental): fresh transfer is not performed, the best quality embryo is cryopreserved. Elective transfer in a later cycle of the cryopreserved embryo. ‐ Group II (control): fresh transfer of the best quality embryo. Subjects of study: Patients who come to the Human Reproduction Unit of the Virgen de las Nieves University Hospital to perform a first or second cycle of IVF / ICSI. Couples will be selected according to inclusion criteria that classify them as good reproductive prognosis (which is consistent with the usual eSET practice). Couples will be able to participate in the study for only one cycle. Each couple will be interviewed to explain the characteristics of the study and will be given an Information Sheet. Written informed consent must be obtained from each couple. The person outside the research team who is guarding the randomization list will assign the corresponding treatment group. Before starting the study, ethical approval was processed by the Ethics Committee through the Ethics Portal for Biomedical Research of Andalusia. For the objective of assesing the null hypothesis that includes the equality of live birth rates in the group of women who undergo an elective deferred transfer of a single embryo and the group who undergo elective transfer of a fresh embryo, a power of 80% has been established to detect statistically significant differences by means of a bilateral Chi‐square test for two independent samples, taking into account that the level of significance is 5%, and assuming that the proportion in the group of women who undergo a fresh transfer is 50.9%, the proportion in the group of women who receive the deferred elective transfer is 78%, and that the proportion of women with respect to the total is 50%, it will be necessary to include 48 women in each group, with the objetive to obtain 96 experimental units in the study. Taking into account that the expected dropout rate is three out of ten women, it will be necessary to include 69 women per group. The 138 women will be assigned to one of the groups using a random procedure, following a sequence of random numbers generated by specific software (Epidat, Epidemiological Data Analysis Program Tabulated. Version 3.1). Methodology The patients must follow an ovulation stimulation treatment, in order to achieve multiple follicular development. A so‐called "long analog" GnRH agonist protocol will be used. This consists of administering from day 22 of the cycle 0.1 mg / day of GnRH analog (Decapeptyl 0.1; Lasa, Barcelona, Spain) until the day on which the administration of gonadotropin is started, in which the dose is reduced at 50% until the day of hCG. After 10‐14 days of administration of the agonist, the pituitary restraint is checked by means of ovarian vaginal ultrasound (absence of follicles and cysts) and serum estradiol determination (<50 pg / mL). If this medical hypophysectomy is confirmed, 300 IU of recombinant FSH (FSHr) is administered per day (Gonal F, Serono, Madrid, Spain) for two days, and 150 IU of FSHr from the 3rd to the 7th day. On this day, ultrasound monitoring of follicular development and serum estradiol determination are performed in order to once again adjust the dose of rFSH to each patient. Once the follicular response is adequate (more than 3 ovarian follicles greater than 18 mm in diameter), ovulation is triggered using 6,500 IU of hCG (Ovitrelle, Merck, Darmstadt Germany). IVF / ICSI and embryo culture will then be performed. To perform sperm microinsemination (ICSI) it is necessary to remove the cumulus and radiated crown from the oocyte. To decumulate, the crown‐oocyte cluster complex is submerged in a solution with 80 IU / mL of hyaluronidase (HYASE, IVF Science Scandinavia, Gothenburg, Sweden) for 10‐20 seconds, aspirating the complex several times using a pasteur pipette. The microinsemination technique is performed under an inverted microscope with Eppendorf and Narishigue micromanipulators and microinjectors. In Vitro Fertilization (IVF) is performed in a five‐well plate, depositing 0.5 mL of IVF medium (Vitrolife, Sweden) and 0.5 mL of Ovoil (Vitrolife, Sweden) in each well. Five cumulus are left per well and 100,000 sperm / mL are added. In both cases, the oocytes are cultured in a Thermo‐Fisher incubator, within a morphokinetic platform (PrimoVision) that takes photographs of them every 5‐10 minutes. The following days are evaluated for classification, choosing the one with the best implantation potential according to the division times measured by morphokinetics and the morphological criteria of the Spanish Association for the Study of Reproduction Biology (ASEBIR) reviewed in 2015. The embryo transfer will be carried out in group 2 on the third day choosing the best embryo according to the previous criteria. In group 1, the embryos will be cryopreserved by vitrification, selecting the best one for delayed transfer. The commercial vitrification media (Medicult Vitrification, Denmark) and the storage device will be Cryoleaf (McGill Cryoleaf, Medicult, Denmark). All cryopreserved embryos will be stored in liquid nitrogen at ‐196ºC in storage cylinders (Air Liquide, France). The day before cryotransfer the embryo is devitrified, using the thawing kit (Medicult Warming, Denmark). At the end, the embryo is washed in G2 medium (Vitrolife), leaving it in culture until the next day, after evaluating the embryo quality and cryosurvival (percentage of lysed cells). The woman's endometrium is prepared by treatment with estradiol valerate and progesterone. On the day of cryotransfer, embryo quality is assessed again, with emphasis on embryo division. Cryotransfer is performed using the same technique as transfer. Study limitations The project has been carried out taking into account the resources available in the Human Reproduction Unit of the University Hospital Virgen de las Nieves, and therefore there do not seem to be any limitations in this regard. The study could be completed by performing a preimplantation genetic diagnosis to determine if there are embryonic genetic alterations prior to intrauterine transfer, but this technique is not yet performed in our Unit. Likewise, blastocyst transfer can increase pregnancy rates, but by increasing the cancellation rate of embryo transfer, so it is not routinely performed in our Unit.

(2023). "Determination of the Effects of Autogenic Relaxation Exercise and Cold Pillow Application on Vasomotor Symptom Control and Quality of Life in Postmenopausal Women."
	Aims:The aim of this study was to determine the effect of autogenic relaxation exercise and cold pillows on vasomotor symptom control and quality of life. Hypothesis:H0‐1: In the postmenopausal period, there was no difference in the frequency of vasomotor symptoms between the group that received autogenic relaxation exercise and cold pillows and the control group. H1‐1: In the postmenopausal period, there is a time difference in vasomotor symptom frequency between the autogenic relaxation exercise and cold pillow group and the control group. H0‐2: In the postmenopausal period, there was no difference in vasomotor symptom duration between the group that was applied autogenic relaxation exercise and cold pillow and the control group. H1‐2: In the postmenopausal period, there is a time difference in vasomotor symptom duration between the autogenic relaxation exercise and cold pillow group and the control group. H0‐3: In the postmenopausal period, there was no difference in vasomotor symptom severity between the groups that received autogenic relaxation exercise and cold pillows and the control group. H1‐3: In the postmenopausal period, there is a time difference in vasomotor symptom severity between the autogenic relaxation exercise and cold pillow group and the control group. H0‐4: In the postmenopausal period, there was no difference in quality of life between the group that was applied autogenic relaxation exercise and cold pillow and the control group. H1‐4: In the postmenopausal period, there is a time difference in quality of life between the group that received autogenic relaxation exercise and cold pillows and the control group. Design: A parelel design randomised controlled study was conducted according to the CONSORT 2010 guidelines. Methods: This study was conducted in Kirikkale University Faculty of Medicine Hospital, Department of Obstetrics and Gynecology, Kirikkale, Turkey between 22.6.2018‐02.01.2019. The sample of the study consisted of women who were in the postmenopausal period, who met the inclusion criteria and who volunteered to participate in the study. Inclusion criteria in the study: Being in the first 5‐year period of postmenopause, experiencing vasomotor symptoms at least twice a day, being at least literate, living within the borders of the center of Kırıkkale province, not having a disease that mimics vasomotor symptoms, not taking hormone therapy other than estrogen in the last 12 months, not using antidepressants and anxiolytics in the last 3 months, not using herbal alternative treatment within the last 4 weeks, women who do not use other alternative and complementary treatment methods, who have a body mass index below 35 and who do not use hormone replacement therapy. Sample: A power analysis was utilised to determine the sample size using the G*Power 3.1.7 program. It was calculated that 61 people should be sampled at a significance level of 0.05 for a minimum power of 90%. In order for the number of people in both groups to be equal, 31 interventions were planned to be included in the sample group of 62 people in 31 control groups. In similar studies in the literature, loss of sample during follow‐up and since it was seen that there was a sample loss during the preliminary application of our research, it was planned to increase the number of samples by 40% and research groups were formed with 44 people in both groups. 142 women were evaluated in terms of suitability for the study, 45 of the women did not meet the inclusion criteria and 88 women could be included in the study because 9 of them did not agree to participate in the study. At different stages of the study, 10 women from the intervention group and 9 women from the control group withdrew from the study. The research was completed with 34 people in the intervention group and 35 people in the control group. After the research was completed, post‐hoc power analysis was performed using the G*power package program and the power of the study was determined as 91% for a sample group consisting of 69 peopl with a significance level of 0.05 for 34 interventions, 35 control groups and an impact width of 0.225. Intention To Treat (ITT) analysis was performed in the study because there were sample losses. Randomisation: Since the sample group was not clear before the study, it was recommended that a total of 4 papers, 2 of which were written as "intervention group" and "control group", were thrown into an envelope during the randomization process and that women should be assigned to the relevant group by selecting a paper from this envelope according to the order of participation in the study. The drawn paper was not thrown back into the envelope until the group of four was finished. After the papers in the envelope were finished, the process of assigning women to the relevant groups continued with the same method. After the women pulled the paper from the envelope, they were asked to give it to the researcher without opening the paper. After the women were invited to the study, they were taken to a separate outpatient clinic room and all procedures (randomly assigned to groups, training, teaching autogenic relaxation exercise, etc.) were performed in this room. The women were not told which group they belonged to during the study. Data collection and outcome measures:The research data were collected using the 'Identifying Features Form', 'Menopause Specific Quality of Life Scale' and 'Vasomotor Symptom and Application Follow‐up Diary'. Introductory features form: In line with the literature were created by researchers with expert opinions. The form includes a total of 28 questions about sociodemographic characteristics, general health status, medical obstetric history and menopausal history. Menopause‐specific quality of life scale: It was developed by Hilditch et al. (1996) to determine the quality of life of women related to menopause and its validity and reliability in Turkish were made by Kharbouch and Şahin (2005). In the Menopause Specific Quality of Life Scale, which consists of 29 items and 4 sub‐dimensions, each sub‐area score is ranked from 0 to 6. A score of "0" indicates that there is no problem with that issue, a score of "1" indicates that the problem is experienced but not at all, and a score of 2‐6 indicates the severity and increasing degrees of the existing problem. The total scale score is not calculated in the Menopause Specific Quality of Life Scale. Scoring is done according to scale sub‐dimensions. Vasomotor symptom and application follow‐up diary: It was created by the researchers to record vasomotor symptoms and relaxation exercise and cold pillow application applied in the research by taking expert opinions in line with the literature. Pilot test: In order to evaluate the intelligibility and usability of the data collection forms, the autogenic relaxation exercise and cold pillow application training booklet and the autogenic relaxation exercise CD to be used in the research, a pre‐application was made on 3 women from the intervention and control groups who met the inclusion criteria of the study. Women with pre‐treatment were not included in the study sample. Intervention group: After the women to be included in the intervention group were determined, individual interviews were held with the women in the room where the orogenic relaxation exercise would be performed. A quiet and dim room has been prepared for relaxation exercise. In the first interview, the introductory characteristics form was filled and the Menopause Specific Quality of Life Scale was completed. In addition, women were given training in line with the training booklet about the menopause period, autogenic relaxation exercise and cold pillow. After the training, autogenic relaxation exercise was taught accompanied by the autogenic relaxation exercise CD. The woman was informed about performing autogenic relaxation exercises 3 times a day and using a cold pillow when she experienced vasomotor symptoms. The autogenic relaxation exercise and cold pad application follow‐up chart, which was prepared for the purpose f recording the applications, was given. The women were evaluated by being invited to the hospital at 4 and 8 weeks, and they filled out the Menopause Specific Quality of Life Scale during the follow‐ups. The intervention was implemented for 8 weeks. Control group:After the women to be included in the control group were determined, individual interviews were conducted with the women in a separate room for orogenic relaxation. In the first interview, the introductory characteristics form was filled and the Menopause Specific Quality of Life Scale was completed. The women were evaluated by being invited to the hospital at 4 and 8 weeks, and they filled out the Menopause Specific Quality of Life Scale during the follow‐ups. The women were followed for 8 weeks. No other intervention was applied to the women other than the standard care they received at the hospital. The women were called every week and their vasomotor symptoms were questioned. Ethical Approval: Institutional and ethical committee permissions were obtained before starting the study (Approval number: 13/01). In addition, written consent was obtained from the scale owner of the scale to be used in the study and the participants who will participate in the study. After the implementation of the study, the women in the control group were given autogenic relaxation exercise and cold pillow application training and training materials. Statistical Analysis:Blinding was done during the evaluation of the data. Intervention and control groups were coded as 1 and 2. The analysis of the data coded in terms of groups was made by the statistician. After the statistical analysis, the coding for the intervention and control groups was explained. Statistical bias was checked with this blanking technique. The research data were transferred to the IBM Statistical Package for Social Sciences (SPSS) 26 program and analyzed. In the study, frequency distributions were used in the evaluation of categorical variables, and descriptive statistics (X̄±SD) were used for numerical variables. The scale sub‐dimension scores of the Menopause Specific Quality of Life Scale, which was used as a measurement tool in the research, were obtained by taking the sum of the related items. The mixed‐pattern anova test was used to test changes or differences in repeated measures of within‐group (in‐group effect), between‐group (time) effect, and co‐effect (group*time effect) repeated measures in intervention and control groups. The margin of error for statistical analysis results was accepted as 5%. In the evaluation of the effect size, the partial η2 value was used (small effect size=0.01, medium effect size=0.06 and large effect size=0.14). The negative (‐) value in front of the effect sizes indicates that the initiatives have a negative effect; a positive (+) value indicates that interventions have a positive effect (230). Intention To Treat (ITT) analysis was performed because there were sample losses in the study. The results of the analyzes (ITT) and Per Protocol (PP) were similar.

(2023). "Different doses of letrozole combined sequentially as letrozole+urofollitropin for treating anovulatory infertility in patients with polycystic ovary syndrome: a pragmatic randomized controlled trial." https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300069638.
	INTERVENTION: Group A:2.5mg+FSH;GroupB:5.0mg+FSH; CONDITION: polycystic ovary syndrome PRIMARY OUTCOME: Ovulation rate;pregnancy rate;Clinical pregnancy rate;ongoing pregnancy rate; INCLUSION CRITERIA: (1) Patients with PCOS who meet the Rotterdam diagnostic criteria in 2003: (1) Patients with rare ovulation or even anovulation; (2) Clinical symptoms or biochemical manifestations of hyperandrogenism; (3) Abdominal ultrasound shows polycystic changes in the ovaries (vaginal ultrasound shows that one or even both ovaries contain more than 12 follicles with a diameter of 2‐9mm). Diagnosis can be made if two of the above three criteria are met. (2) Patients under 40 years old, with normal sexual activity and infertility for at least 1 year. (3) Hysterosalpingography shows normal uterine morphology and at least one patent fallopian tube. (4) The results of the spouse's semen analysis are normal or mildly oligoasthenozoospermia. (5) All organ functions are normal and there are no accompanying endocrine diseases such as pituitary dysfunction or hyperthyroidism. (6) The patient has been fully informed of the nature, significanc

(2023). "Effect duloxetine versus amitriptyline on clinical outcomes of female with chronic pelvic pain syndrome."
	INTERVENTION: Intervention 1: Intervention group: Duloxetine tablets 30 mg daily for one week then 60 mg daily for 8 weeks. Intervention 2: Control group: Amitriptyline tablets 25 mg daily for one week then 50 mg daily for 8 weeks. CONDITION: Chronic pelvic pain syndrome. ; Pelvic and perineal pain R10.2 PRIMARY OUTCOME: Improvement of clinical symptoms (pain, difficulty in defecation). Timepoint: Before the intervention and one and two months after that. Method of measurement: Using the National Institutes of Health Chronic Syndrome Symptom Index (NIH‐CSSI). The rate of overall response to treatment. Timepoint: Two months after the intervention. Method of measurement: Using the Global Response Assessment (GRA) questionnaire. SECONDARY OUTCOME: Occurrence of side effects (nausea, vomiting). Timepoint: one and two months after intervention. Method of measurement: With history taking. INCLUSION CRITERIA: Age 18 to 50 years Chronic pelvic pain syndrome for more than 6 months

(2023). "Effect of endometrial Scratching on pregnancy outcome after intrauterine insemination."
	INTERVENTION: Intervention 1: Endometrial scratching intervention group: Endometrial scratching is done in the intrauterine sperm injection (IUI) cycle on day 5 or 6 from the beginning of the menstrual cycle. To perform endometrial scratching, the patient is placed in a lithotomy position. Then, the speculum is slowly placed in the vagina to expose the cervix, and with the use of a flexible catheter, the endometrium is scratched in a circular position after performing aspiration. The circular movement of the catheter starts and ends in 12 o'clock position, and then the catheter is removed. If the catheter does not pass through the tenaculum, the anterior edge of the cervi Xis used to grasp the. According to the level of Anti‐Müllerian Hormone (AMH) and Ovarian Reserve Count (AFC), letrozole, Cinnal F, or Menstrual Gonadotropin (HMG) is used to stimulate the ovaries, depending on the initial response to stimulation. After starting the drugs, the follicle size is monitored. When the size of the follicles is greater than or equal to 18, two ampoules of human chorionic gonadotropin (HCG) are prescribed to release the egg, and the patient undergoes IUI after 36 hours. Intervention 2: Control group: Patients in this group will undergo a vaginal examination with a speculum and a cervical scraper will enter into the posterior forni Xwithout scratching. According to the level of Anti‐Müllerian Hormone (AMH) and Ovarian Reserve Count (AFC), letrozole, Cinnal F, or Menstrual Gonadotropin (HMG) is used to stimulate the ovaries, depending on the initial response to stimulation. After starting the drugs, the follicle size is monitored. When the size of the follicles is greater than or equal to 18, two ampoules of human chorionic gonadotropin (HCG) are prescribed to release the egg, and the patien CONDITION: Infertility needs intrauterine insemination (IUI). ; Artificial insemination Z31.1 PRIMARY OUTCOME: Clinical pregnancy rate. Timepoint: 5‐6 weeks after IUI. Method of measurement: Transvaginal sonography. SECONDARY OUTCOME: Chemical pregnancy rate. Timepoint: 14 days after IUI. Method of measurement: Measurement of beta human chorionic gonadotropin serum level (Beta HCG). Live birth rate. Timepoint: 28 weeks of pregnancy. Method of measurement: Phone based interview. INCLUSION CRITERIA: Age 20‐42 year Unexplained infertility or mild male factor infertility Failure of at least two previous intrauterine insemination (IUI) cycles

(2023). "The Effect of Escitalopram in PCOS." https://clinicaltrials.gov/show/NCT05840692.
	Clinical study Effects of antidepressive treatment on quality of life, insulin sensitivity and cortisone metabolism in PCOS. Hypothesis Participants with PCOS have increased hypothalamic‐pituitary‐adrenal activity compared to healthy women. Antidepressive treatment improves quality of life, cortisone and glucose turnover. Design A randomized controlled study in 40 PCOS patients who are treated with cipralex or placebo for 12 weeks. Before and after the treatment period the patients have a physical examination, a whole body dexa scan and fasting blood samples. Hypothalamic‐pituitary‐adrenal is measured by 24 hour samples of cortisone metabolites, 60 minutes ACTH test with basal and stimulated measurement of cortisone and 17‐hydroxyprogesterone. Glucose metabolism is examined by oral glucose tolerance test. Biopsies of muscle and fat are also performed.

(2023). "The effect of Fasting-mimicking diets on polycystic ovary syndrome." https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300071796.
	INTERVENTION: control:Nil;Interventional group:fasting‐mimicking diet; CONDITION: polycystic ovary syndrome PRIMARY OUTCOME: Recovery of menstrual patterns; SECONDARY OUTCOME: luteinizing hormone (LH);follicle‐stimulating hormone (FSH);Estradiol (E2);Testosterone (T);Prolactin (PRL);progesterone (PROG);Fasting insulin (FINS);Fasting Plasma Glucose;Total cholesterol (TC);Triglyceride (TG);high density lipoprotein (HDL);low density lipoprotein (LDL);Insulin resistance inde X(HOMA‐IR); INCLUSION CRITERIA: 1. Female patients who meet the diagnostic criteria for PCOS in the Diagnostic Criteria and Treatment Specifications for Polycystic Ovary Syndrome formulated by Chinese experts in 2011; 2. Aged 18‐40 (Inclusion boundary value); 3. BMI: 20‐40 kg/m2 (Inclusion boundary value); 4. Patients who are willing to accept the diet intervention program; 5. Patients who volunteered to participate in this study and signed informed consent.

(2023). "The effect of grape seed extract vaginal cream on the treatment of candidal vaginitis." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20181214041963N3.
	INTERVENTION: Intervention 1: Intervention group: grape seed cream, which will be made in Jundishapur Faculty of Pharmacy of Medical Sciences. To prepare medicine, 35 empty metal tubes of 50 grams with 2% grape seed cream will be prepared and filled with 50 grams of tube from Tolo Gostar Bukhara company/along with an applicator/one applicator should be used inside the vagina every night for seven days. Intervention 2: Control group: Clotrimazole vaginal cream 2%, which will be manufactured in Jundishapur Faculty of Pharmacy, along with an applicator, one applicator should be used inside the vagina every night for seven days. CONDITION: B37.3 Candida vaginitis. ; Candidiasis of vulva and vagina PRIMARY OUTCOME: Improvement of candidiasis signs. Timepoint: 6‐8 next days. Method of measurement: Examination and laboratory test and check list. SECONDARY OUTCOME: Improvement of disease recurrence. Timepoint: 40 days after the intervention. Method of measurement: Examination and laboratory test and checklist. INCLUSION CRITERIA: Consent to participate in research Diagnosis of candidal vaginitis (at least 3 points out of 18 symptom points), Marriage history Not being pregnant Lack of breastfeeding Not suffering from diabetes mellitus and diseases that weaken the immune system Not using broad‐spectrum antibiotics in the last 2 weeks Not using vaginal douche in the last 48 hours Not using vaginal drugs during the last week Not using hormonal drugs during the last 3 months Not having audio Not having a candidal infection more than 4 times a year

(2023). "Effect of Huoshan Dendrobium Zengye Jiedu Formula on oral mucositis and quality of life in patients with radiotherapy and chemotherapy."
	INTERVENTION: Experimental group:Huoshan Dendrobium Zengye Jiedu Formula;Control group:Kangfuxin liquid; CONDITION: Oral mucositis PRIMARY OUTCOME: Pain digital scoring;Inappropriate score;WHO classification of oral mucositis;Core scale score of quality of life for cancer patients;Immune function test; SECONDARY OUTCOME: Tumor markers;routine blood test; INCLUSION CRITERIA: 1. The age is 18‐80 years old, regardless of gender; 2. Patients with oral mucositis diagnosed clinically; 3. Patients with advanced malignant tumors confirmed by cytology or histology pathology are head and neck tumors (including nasopharyngeal cancer, esophageal cancer, etc.), lung cancer, stomach cancer, ovarian cancer, breast cancer, cervical cancer, etc. TNM stage is ? ‐ ?; ECOG score 0 1; The expected survival period is more than 6 months; 4. Those who have experienced radiotherapy or chemotherapy or concurrent radiotherapy and chemotherapy (the chemotherapy plan includes at least one or more of cyclophosphamide, methotrexate, nitrogen mustard, cisplatin, gemcitabine, cytarabine, vinblastine, podophyllotoxin, paclitaxel and other drugs) shall undergo chemotherapy; 5. The patient has clear consciousness, language expression ability or reading ability, can communicate normally, and can cooperate to complete the assessment; 6. Volunteer to join

(2023). "effect of LigaSure on post hysterectomy pain."
	INTERVENTION: Intervention 1: The first group are patients who undergo hysterectomy surgery with ligature for non‐malignant reasons. Pain after surgery 6 hours and 24 hours after surgery is compared with the opposite group that undergoes hysterectomy with the conventional method. Also, the length of stay in the hospital and the amount of painkillers used will be measured together. The amount of bleeding during the operation will also be compared between the two groups. Also, the return time of bowel function, complications such as urinary retention, re‐hospitalization due to the complications of the operation will be measured. will be compared. Intervention 2: Control group: The first group is the patients who undergo hysterectomy with conventional method for non‐malignant reasons. Pain after surgery 6 hours and 24 hours after surgery is compared with the opposite group that undergoes hysterectomy with the conventional method. Also, the length of stay in the hospital and the amount of painkillers used will be measured together. The amount of bleeding during the operation will also be compared between the two groups. Also, the return time of bowel function, complications such as urinary retention, re‐hospitalization due to the complications of the operation will be measured. will be compared. CONDITION: Hysterectomy. ; absence of both cervi Xand uterus Z90.710 PRIMARY OUTCOME: Post operation Pain. Timepoint: 6 hours after ending surgery and 24 hours after ending surgery. Method of measurement: Scale of Clinical Quality Indicators Postoperative Pain (SCQIPP) tool. The number of pain killer administration post surgery. Timepoint: During 48 hours after ending surgery. Method of measurement: Documented in medical record. SECONDARY OUTCOME: Duration of hospitalization of patient. Timepoint: The number of days of hospitalization after surgery. Method of measurement: Medical Record sheets. Duration of surgery. Timepoint: From surgery incision till end of closing it. Method of measurement: Stopwatch. The first time after surgery that patient will go out of bed. Timepoint: during 24 hours after surgery. Method of measurement: documented in medical record sheets by healthcare providers. INCLUSION CRITERIA: patients who candidate for hysterectomy with non malignant reason

(2023). "Effect of long snake moxibustion combined with pelvic floor muscle training on BND and PUVA in patients with stress urinary incontinence of kidney-yang deficiency type."
	INTERVENTION: Observation group:Long snake moxibustion combined with pelvic floor muscle training;Control group:Pelvic floor muscle training; CONDITION: Stress urinary incontinence PRIMARY OUTCOME: 1h urine pad test;incontinence impact questionnaire short form;Values of bladder neck mobility and posterior vesicourethral angle; INCLUSION CRITERIA: 1. Meet the diagnostic criteria of appeal; 2. Multiparous women aged 30‐60 years; 3. Mild to moderate stress urinary incontinence; 4. Voluntarily participate in the study and sign the informed consent form; 5. No treatment for the disease or take drugs affecting lower urinary tract function in the past 1 month.

(2023). "Effect of Marma Chikitsa on Udavarta Yoni Vyapad (Primary dysmenorrhea."
	INTERVENTION: CONDITION: Health Condition 1: N944‐ Primary dysmenorrhea Health Condition 2: N944‐ Primary dysmenorrhea PRIMARY OUTCOME: It is expected that at the end of study, scholar will be able to evaluate the effect of Marma Chikitsa in the management of Udavarta Yoni Vyapad ( Primary Dysmenorrhea). ; Spasmodic pain ; Cramping in the lower abdomen ; Pain radiate to lower back and medial aspect of thighs ; ; Timepoint: It is expected that at the end of 2 month, scholar will be able to evaluate the effect of Marma Chikitsa in the management of Udavarta Yoni Vyapad ( Primary Dysmenorrhea). ; Spasmodic pain ; Cramping in the lower abdomen ; Pain radiate to lower back and medial aspect of thighs ; ; SECONDARY OUTCOME: It is expected that at the end of study, scholar will be able to evaluate the effect of Marma Chikitsa in the management of Udavarta Yoni Vyapad ( Primary Dysmenorrhea).Timepoint: It is expected that at the end of 1 month and 1 month follow up, scholar will be able to evaluate the effect of Marma Chikitsa in the management of Udavarta Yoni Vyapad ( Primary Dysmenorrhea). INCLUSION CRITERIA: â?¢Patient between the age of 14‐30 years. â?¢Patient which fall under the diagnostic criteria. â?¢Patient with complaint of painful menstruation but without pelvic pathology. â?¢Pain along with scanty or average amount of blood flow. â?¢Patient willing to be registered for study with written consent.

(2023). "Effect of Palashudumbaradi Lepam followed by Kapikacchu mooldhavanam along with yogic practices in Pelvic Organ Prolapse."
	INTERVENTION: CONDITION: Health Condition 1: N812‐ Incomplete uterovaginal prolapse PRIMARY OUTCOME: To reposition the prolapsed uterus and vagina into its original positionTimepoint: 3 months SECONDARY OUTCOME: relief in associated features like difficulty in micturition,dyspareunia,backache,vaginal dischargesTimepoint: 3 months INCLUSION CRITERIA: 1.Patients having sign and symptoms of 1st and 2nd degree uterine prolapse 2.Patient having signs and symptoms of cystocele and rectocele 3.Patients with complaints of difficulty in micturition,incomplete emptying of bladder,dyspareunia 4.Patient having signs and symptoms of laxity of perineum

(2023). "The Effect of Symptom Management Program Based on Story Theory on Vasomotor Symptoms and Sleep Quality in Postmenopausal Women." ClinicalTrials.gov.
	Purpose: To investigate the effect of the Symptom Management Program Based on Story Theory on vasomotor symptoms and sleep quality in postmenopausal women. Design: The type of this research is mixed method (qualitative and quantitative research design together). It enables to strengthen the weaknesses of mixed method research, to increase the generalizability of the results, and to produce more reliable outputs regarding theory and practice. The quantitative research dimension is a randomized single-blind pretest-posttest experimental model with a control group. The qualitative research dimension is the descriptive phenomenological design. Method: The research will be carried out at Ömürevleri, Atakum, Mimar Sinan, Çobanlı and Yenimahalle Family Health Centers located in different regions of the Atakum District of Samsun. After informing the women who come to the Family Health Centers about the face-to-face research, the research will be conducted completely online (due to the COVID-19 pandemic) after the verbal consent of the women who volunteered to participate in the research and their contact numbers are obtained. The postmenopausal women who apply to the institutions where the research will be conducted and meet the inclusion criteria constitute the population of the research. When the sample size calculated with the G.Power program was taken as Pittsburgh Sleep Quality Index score mean and standard deviation value as 6.57±1.23, with 5% significance level, 80% test power, 0.700 effect size, there were at least 68 groups, 34 for the experimental group and 34 for the control group. identified as a person. Considering the sample loss in the experimental and control groups, with 10% more sampling, a total of 76 women will be included in the sample, with 38 women in each group. n the study, the data will be collected with the Personal Information Form, the Menopause Symptoms Assessment Scale, the Pittsburgh Sleep Quality Index and the Story Theory Based Semi-Structured Interview Form (for qualitative research) developed by the researchers in line with the literature. As a result of the study, the data will be evaluated separately as qualitative and quantitative.

(2023). "The effect of yoga training program on pelvic floor muscle strength, bladder neck descent,urinary control, urogenital hiatus diameter and urethral rotation angles in female athletes with stress urinary incontinence due to training intensity." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20230113057119N1.
	INTERVENTION: Intervention 1: Intervention: Yoga exercises group. After checking the records and evaluation using the form to collect information such as age, sports history, pregnancy history, disease history and drug use, etc and the international form of urinary incontinence from the patients,10 people will be selected with stress urinary incontinence. Then these people will be invited by signing the consent form. until the pre‐test (quality of life questionnaire, two‐dimensional ultrasound of pelvic floor muscles and clinical assessment of vaginal touch) and after the implementation of yoga rehabilitation exercise program to strengthen pelvic floor muscles and core muscles and breathing exercises for eight weeks in three sessions An hour and a quarter per week and in each session, a post‐test (quality of life questionnaire, two‐dimensional ultrasound of the pelvic floor muscles and clinical assessment of vaginal palpation) is performed. Intervention 2: Intervention: Yoga exercises group. After checking the records and evaluation using the form to collect information such as age, sports history, pregnancy history, disease history and drug use, etc and the international form of urinary incontinence from the patients,10 people will be selected with stress urinary incontinence. Then these people will be invited by signing the consent form. until the pre‐test (quality of life questionnaire, two‐dimensional ultrasound of pelvic floor muscles and clinical assessment of vaginal touch) and in these four weeks he continued with his routine activities and finally a post‐test (quality of life questionnaire, two‐dimensional ultrasound of the pelvic floor muscles and clinical assessment of vaginal palpation) is performed. CONDITION: N39.3 Stress Urinary Incontinence (SUI). ; Stress incontinence (female) (male) PRIMARY OUTCOME: Urinary Incontinence. Timepoint: Before eight weeks of yoga and after eight weeks of yoga. Method of measurement: Incontinence Questionnaire–Urinary Incontinence Short Form (ICIQ‐UI SF). SECONDARY OUTCOME: Angles of rotation of the urethra. Timepoint: Before and after eight weeks of yoga. Method of measurement: Ultrasound. Bladder neck descent. Timepoint: Before and after eight weeks of yoga. Method of measurement: Ultrasound. Pelvic floor muscle strength. Timepoint: Before and after eight weeks of yoga. Method of measurement: Vaginal touch clinical test. The diameter of the urogenital hiatus. Timepoint: Before and after eight weeks of yoga. Method of measurement: Ultrasound. Urinary Incontinence Quality Of Life. Timepoint: Before and after eight weeks of yoga. Method of measurement: Incontinence Quality Of Life(IQOL). INCLUSION CRITERIA: be a woman Suffering from stress urinary incontinence Sports history Have not done yoga for at least si Xmonths

(2023). "Effectiveness of an EMDR Intervention for Perinatal Loss."
	Perinatal loss is a general term that refers to a loss from conception to one month postpartum. It is a grief that is still socially unauthorized, however, it is a situation with significant traumatic potential. However, there are no studies evaluating the effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) for the prevention or treatment of perinatal loss. We propose an one‐site, open label, randomized controlled trial with the aim of assessing the effectiveness of EMDR recent traumatic episode (EMDR‐RTE) as a preventive intervention for PTSD symptoms after perinatal loss. A total of 40 women who have suffered a perinatal loss from the Maternal‐Fetal Medicine Service of a tertiary university hospital will be recruited. Women will be randomized to EMDR‐RTE or treatment as usual (TAU). Researchers will compare EMDR‐RTE and TAU to see if women receiving EMDR‐RTE treatment had lower levels of post‐traumatic and depressive symptoms.

(2023). "Effectiveness of platelet-rich plasma injection in treatment of stress urinary incontinence."
	INTERVENTION: Intervention 1: Intervention group: 24 patients undergoing pelvic floor muscle rehabilitation treatment as 35‐minute sessions, once a week, including 20 minutes of electrical stimulation with a vaginal probe with biphasic alternating current settings with a frequency of 5 Hz and a pulse width of 300 microseconds and current intensity from 1 to 100 The milliampere is adjusted to the level tolerated by the patient. Then 15 minutes of biofeedback with pelvic floor rehabilitation protocol will be performed for the patient in 4 weekly sessions (one session per week) for one month. In between sessions, the patient should perform Kegel exercises 6 times a day. In this group, after 4 sessions of pelvic rehabilitation, one shot of platelet‐rich plasma in the anterior 1/3 wall of the vagina is performed. Three shots of platelet‐rich plasma are performed at 4‐week intervals. Before performing the procedure, a full blood test will be performed for the patients for platelet count, prothrombin time and check liver enzymes to rule out liver diseases, and a complete urine test. Then the injection process will be explained to the patients and patients with the following abnormalities will be excluded from the trial: 1‐ Platelet disorders 2‐ Thrombocytopenia 3‐ Hypofibrinogenemia 4‐ Patients who are not hemodynamically stable 5‐ Acute/chronic infection 6‐ Chronic liver disease 7‐ Patients who use anticoagulants 8‐ Malignancy. Eligible patients will be referred to the pain and rehabilitation clinic, and after obtaining informed consent from the patients, two 10 ml samples of blood will be taken, and after centrifugation, two 5 ml samples of platelet‐rich plasma will be prepared for administration. Gel‐based Royagen kits will be used to prepare platelet‐rich plasma. The procedure is done w CONDITION: N39.3 Stress urinary incontinence. ; Stress incontinence (female) (male) PRIMARY OUTCOME: Stress urinary incontinence. Timepoint: The effectiveness of platelet‐rich plasma injection and pelvic floor biofeedback after 4 weekly sessions of biofeedback and 3 monthly sessions of PRP shots on women suffering from stress urinary incontinence. Method of measurement: International Consultation on Incontinence Questionnaire‐ Female Lower Urinary Tract Symptom (ICIQ‐FLUTS) long form and short form. SECONDARY OUTCOME: Quality of life. Timepoint: The effectiveness of platelet‐rich plasma injection and pelvic floor biofeedback after 4 weekly sessions of biofeedback and 3 monthly sessions of PRP shots on quality of life of women suffering from stress urinary incontinence. Method of measurement: International Consultation on Incontinence Questionnaire‐ Quality of Life (ICIQ‐QOL). Sexual Function. Timepoint: The effectiveness of platelet‐rich plasma injection and pelvic floor biofeedback after 4 weekly sessions of biofeedback and 3 monthly sessions of PRP shots on sexual function of women suffering from stress urinary incontinence. Method of measurement: Female Sexual Function Inde XPelvic incontinence Sexual Questionnaire‐12. INCLUSION CRITERIA: Women with clinical symptoms of urinary incontinence. Age 35‐55 patients opting for non‐surgical management.

(2023). "Effects of intermittent fasting on quality of life and toleance of chemotherapy in patients with gynaecological cancers: a randomized-controlled multi-center study."
	INTERVENTION: Group 1: Intermittent fasting (16:8h) over a period of three months during chemotherapie, has to be performed at at least 5 of 7 days per week, no food intake allowed on day of chemotherapy Group 2: Normal diet during chemotherapy (encouraged to follow a healthy, mediterranean diet CONDITION: ; C50 ; C56 ; C54.1 ; C53 C54.1 Endometrium Malignant neoplasm of breast Malignant neoplasm of cervi Xuteri Malignant neoplasm of ovary PRIMARY OUTCOME: Changes in fatigue measured by the FACIT‐FS questionnaire during 3 months of chemotherapy. The questionnaire will be assessed weekly to evaluate changes in fatigue during the chemotherapy cycle. SECONDARY OUTCOME: Secondary, explorative clinical endpoints: ; ‐ General Quality of Life: measured by the FACT‐G questionnaire and tumorspecific FACT questionnaires, as well as the general wellbeing questions of the EORTC QLQ C30 questionnaire; weekly recording of changes ; ‐ Sleep Quality: measured by the Pittsburgh Sleep Quality Index, recorded at baseline, 3 months and 6 months ; ‐ Pelvic floor function: measured by the German pelvic floor questionnaire, recorded at baseline, 3 months and 6 months ; ‐ Chemotherapy associated side effects: measured by CTCAE criteria, recorded at every cycle ; ‐ Weight changes: measured by body weight every cycle ; ‐ Laboratory changes (metabolic and organ function): measurment of different values at different time points, blood draws weekly ; ‐ Tumor response: tumormarker every 3 months, radiological tumor response measured by RECIST 1.1 every 3 months in metastasized patients, pathological tumor response post‐surgery in neoadjuvantly treated patients ; ; Secondary, explorative laboratory endpoints: ; ‐ Changes in immunological cells: Composition of peripheral blood mononuclear cells at baslien, 7 weeks and 13 weeks ; ‐ Peripheral cell damage: measured by yH2A Xintensity 3h after the start of chemotherapy at cylce 1, 6 weeks and 12 weeks ; INCLUSION CRITERIA: ‐ Gynaecological cancers (ovarian/endometrial/cervical/breast) ‐ BMI = 19 kg/m2 ‐ Baseline ECOG Status 0‐2 ‐ Life expactancy of over 6 months ‐ No i.v. chemotherapy in last 3 months ‐ Planned to recieve chemotherapy with at least one topoisomeraseinhibitor or alkylating agent over a period of three months ‐ Ability to understand the meaning and effects of the trial

(2023). "Effects of Muscle Energy Techniques Versus Core Stability Exercises in Pelvic Girdle Pain."
	Pelvic girdle pain (PGP) is known to be a musculoskeletal disorders which affects the pelvic bone. PGP is referred to as a specific form of LBP which occurs isolatedly as well as in combination with lumbar back pain. PGP localized to the anterior or posterior pelvis, most commonly located between the posterior iliac crest and gluteal folds especially around the SI joint. Pelvic girdle pain radiated to the posterior thigh. Moreover, it can also cause pain in the symphysis (1). Compared to lower back pain, PGP is substantially more painful and linked with functional limitations as standing, walking, sitting and changing positions are less tolerable in such patients (2). PGP is musculoskeletal in nature and is not caused by gynecological or urological conditions (3). Despite the fact that the cause of PGP is unknown, it is considered that it occurs due to many reasons such as trauma, arthritis, anatomical fault or it can be associated with pregnancy (4

(2023). "Effects of Pelvic Floor Muscle Training."
	INTERVENTION: Intervention 1: Intervention group: The protocol consisted of pelvic floor muscle strengthening exercises. Women were encouraged to perform three sets of ten slow contractions, holding each contraction for 6 to 8 seconds, followed by a rest period equal to the duration of the contraction. and finally three to four rapid contractions are performed in supine, sitting and standing positions for at least three times a day. Mothers do these exercises for 10 consecutive weeks (25 weeks of pregnancy to 35 weeks of pregnancy) and gradually the number of contractions increases. In each exercise, pay attention that the muscles of the pelvic floor are contracted and the muscles of other parts of the pelvis are relaxed. During the research, the examiner communicates with the mother two days a week through social networks and phone calls. Intervention 2: Control group: This group will be given the usual recommendations for care during this period and pelvic floor strengthening exercises in the form of pamphlets. CONDITION: N39.3 Urinary incontinence. ; Stress incontinence (female) (male) PRIMARY OUTCOME: Comparison of bladder base displacement with ultrasound to evaluate the strength of the pelvic floor muscles. Timepoint: Measuring of bladder base displacement at the beginning of the third trimester (28‐25 weeks), late third trimester (35‐32 weeks). Method of measurement: Measurement of bladder base displacement by ultrasound. SECONDARY OUTCOME: Measurement of quality of life. Timepoint: Early third trimester (25‐28 weeks), late third trimester (35‐32 weeks). Method of measurement: Measurement of quality of life with incontinence quality of life (I‐QOL) questionnaire. INCLUSION CRITERIA: First pregnancy Gestational age of 25 week Presence of urinary incontinence Gestational diabetes mellitus

(2023). "Efficacy and safety of remazolam in hysteroscopy."
	INTERVENTION: Remazolam group and propofol group:The induction dose of rimazolam was 0.2mg/kg/min, and MOAA/S score was performed every 20 seconds. When MOAA/S=1, the maintenance dose was adjusted by 1 mg/kg/h, and surgery was started.;propofol group :The induced dose of propofol is 2mg/kg/min, and the MOAA/S score is performed every 20 seconds. When the MOAA/S = 1 minute, the maintenance dose is adjusted to 2mg/kg/h, and the operation is started; CONDITION: Endometrial lesions PRIMARY OUTCOME: onset time;Awakening time;Departure time; SECONDARY OUTCOME: Drug dosage;Incidence rate of adverse events; INCLUSION CRITERIA: Patients aged 18‐65, ASA grade I‐II, body mass inde X(BMI)18‐30kg/m2, selected for hysteroscopy, volunteered to participate in the study and signed informed consent, willing to comply with the study requirements.

(2023). "efficacy of hyoscine on dilation of the cervix."
	INTERVENTION: Intervention 1: Intervention group: The intervention group is candidate to receive hyosine vaginal tablets. 2 hours before the hysteroscopy procedure, two hyoscine tablets (10 mg, manufactured by Porsina Pharmaceutical Company) are given to each patient intravaginally. Intervention 2: Control group: There is no intervention for the control group. CONDITION: Menopausal women. ; Unspecified menopausal and perimenopausal disorder N95.9 PRIMARY OUTCOME: Cervical dilation. Timepoint: 2 hours after medication. Method of measurement: bogie number 4. SECONDARY OUTCOME: Hyoscine side effect. Timepoint: after operation. Method of measurement: physician submission. INCLUSION CRITERIA: Patient's willing to participate in study Menopausal women who are planed for hysteroscopy and dilator number 4 does not pass from cervix Negative past cervical surgery Negative allergy history about Hyoscine Negative past medical history about cancers, obstructive bowel disease and cardiopulmonary disease

(2023). "efficacy of lignocaine in distension medium to reduce pain perceived during office hysteroscopy."
	INTERVENTION: Intervention1: diagnostic hysteroscopy: efficacy of lignocaine in distension medium in improving pain score‐ during office hysteroscopy Control Intervention1: comparing pain: efficacy of lignocaine in distension medium in improving pain score‐ during office hysteroscopy pain is assessed by VAS score taking case and control. CONDITION: Health Condition 1: N939‐ Abnormal uterine and vaginal bleeding, unspecified Health Condition 2: N00‐N99‐ Diseases of the genitourinary system Health Condition 3: N921‐ Excessive and frequent menstruation with irregular cycle Health Condition 4: N920‐ Excessive and frequent menstruation with regular cycle Health Condition 5: N972‐ Female infertility of uterine origin Health Condition 6: N979‐ Female infertility, unspecified Health Condition 7: N926‐ Irregular menstruation, unspecified Health Condition 8: N915‐ Oligomenorrhea, unspecified Health Condition 9: N950‐ Postmenopausal bleeding Health Condition 10: N96‐ Recurrent pregnancy loss Health Condition 11: N911‐ Secondary amenorrhea Health Condition 12: N959‐ Unspecified menopausal and perimenopausal disorder PRIMARY OUTCOME: efficacy of lignocaine in distension medium in improving pain score during office hysteroscopyTimepoint: 5 minutes prior procedure ; during procedure ; 5 minutes after procedure SECONDARY OUTCOME: efficacy of lignocaine in distension medium in improving pain score during office hysteroscopyTimepoint: 5 minutes prior procedure ; during procedure ; 5 minutes after procedure INCLUSION CRITERIA: 1.All women aged 20‐55 years undergoing office hysteroscopy(AUB, Infertility, Recurrent pregnancy loss etc.) 2.willing to participate and sign informed written consent 3.participants falling in ASA I&II

(2023). "Efficacy of Low-intensity Shockwave vs Radial Wave for Treatment of Erectile Dysfunction and Pelvic Pain."
	After being informed about the study and potential risks, all patients giving written informed consent will undergo screening to determine eligibility for study entry. Participants who meet eligibility requirements will be randomized in a double blind manner (participant and investigator) to each treatment arm depending on their primary complaint. Participants with erectile dysfunction will be randomized 2:2:1 to either fSWT, rWT or sham therapy. Patients with chronic pelvic pain syndrome will be randomized 1:1 to either fSWT with pelvic floor physical therapy (PFPT) or PFPT with sham treatment.

(2023). "Efficacy of Percutaneous Electrical Neurostimulation(PENS) of the Auricle as an Opioid Sparing Postoperative Analgesic Technique in Cancer Endometrium and Cancer Cervix Patients."
	Efficient post operative pain relief is an essential part of comprehensive recovery of patients. Conventional method of pain management of laparotomy surgeries in CA endometrium and cervix patients involves invasive techniques like epidural or selective nerve block coupled with a varied choice of analgesics like opioids, NSAID or acetaminophen, wherein each drug is associated with its own set of contraindications and side effects. Despite advances in analgesic regimen including multimodal analgesic regimen, opioids have been observed to remain the mainstay postoperative analgesia in cancer patients despite its well‐established side effects. This double‐blinded prospective interventional study is conducted to explore the alternative of percutaneous electrical nerve stimulation (PENS) devices for effective pain relief with minimal to no side‐effects. The device will have tiny needles and a battery system that will be placed on and behind the patient's ear when they are under anesthesia. It acts by stimulating nerves around ear region by series of pain free impulse generation leading to centrally (brain) mediated response by altering certain chemical substances responsible for causing pain thereby providing relief for the patient.

(2023). "Efficacy of vasopressin for adhisionolysis of bowel DIE in laparoscopy."
	INTERVENTION: Intervention 1: Intervention group: In intervention group 50 patients will allocated and diluted injection vasopressin in 200 cc normal salin will injected in low posterior wall of uterus. Bleeding, ease of adhesion dissection, surgical complications will be recorded. Intervention 2: Control group: 5o patients randomly will assigned in control group who received injection of normal salin in the site of adhesion. Bleeding, ease of adhesion dissection, surgical complications will be recorded. CONDITION: Severe endometriosis. ; N97.8 PRIMARY OUTCOME: Time of surgery,Bleeding,bowel injury, ease of dissection. Timepoint: After surgery. Method of measurement: Questionnaire. SECONDARY OUTCOME: Dysmenorrhoea, dysparunia,chemical pregnancy, clinical pregnancy. Timepoint: 3‐6 months after surgery. Method of measurement: Questionnaire,bhcg test. INCLUSION CRITERIA: Age 20‐50 Stage 3‐4 endometriosis according to ASRM Severe adhesion in pelvis

(2023). "Electroacupuncture for chronic pelvic pain(CPP),sequela of pelvic inflammatory disease (PID)."
	INTERVENTION: Electroacupuncture group:Electroacupuncture treatment;Drug group:Take ibuprofen orally; CONDITION: chronic pelvic pain(CPP),sequela of pelvic inflammatory disease (PID) PRIMARY OUTCOME: Visual analog scale; SECONDARY OUTCOME: Self‐Rating Anxiety Scale;Self‐Rating Depression Scale; INCLUSION CRITERIA: Conform to the diagnostic criteria of chronic pelvic pain due to sequela of pelvic inflammatory disease; Women aged 20‐50 years with a history of sexual life, have relatively regular menstrual cycles; Visual analog scale (VAS) score of lower abdomen and lumbosacral pain = 3 points; Able to follow the test regulations and sign the informed consent form.

(2023). "empagliflozin effect in polycystic ovarian syndrom."
	INTERVENTION: Intervention 1: Intervention group: The people of this group are given empagliflozin 10 mg tablets (ABIDI company) once a day for three months. Intervention 2: Control group: The people of this group were given 1000 mg metformin tablets (Rahadaroo company) once a day for three months. CONDITION: E28.2 Polycystic ovarian syndrome. ; Polycystic ovarian syndrome INCLUSION CRITERIA: women between 15‐55 years old polycystic ovarian syndrom PRIMARY OUTCOME: 17‐oh progesterone. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ELISA. Alanine transaminase(ALT). Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ELISA. AST (aspartate aminotransferase). Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ELISA. Body mass index. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: Meter and scale. C‐reactive protein (CRP). Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ELISA. Dehydroepiandrosterone. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ELISA. Fasting blood sugar. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: spectrophotometry. Fasting insulin. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ELISA. Hba1c. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: HPLC. HDL (high‐density lipoprotein). Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: spectrophotometry. Insulin resistance. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: HOMA.IR. LDL (low‐density lipoprotein). Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: spectrophotometry. Total cholestrol. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: spectrophotometry. Total testestrone. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: ECLIA. Triglycerides. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: spectrophotometry. Waist circumfernce. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: Measuring tape. Weight. Timepoint: before the start of the intervention and three months after the start of the intervention. Method of measurement: Digital scale.

(2023). "Erratum: effect of Zuranolone vs Placebo in Postpartum Depression: a Randomized Clinical Trial (JAMA Psychiatry (2021) 78: 9 (951-959) DOI: 10.1001/jamapsychiatry.2021.1559)." JAMA Psychiatry 80(2): 191.
	Error in Results: In the Original Investigation titled “Effect of Zuranolone vs Placebo in Postpartum Depression: A Randomized Clinical Trial,”1 published in the September 2021 issue, there was an error in the Results section. The number of patients in the zuranolone and placebo groups who had new antidepressantmedication treatment initiatied by investigators were switched and should be 6 and 4, respectively. This article has been corrected online.

(2023). "Erratum: efficacy and safety of weekly paclitaxel plus vistusertib vs paclitaxel alone in patients with platinum-resistant ovarian high-grade serous carcinoma: the OCTOPUS multicenter, phase 2, randomized clinical trial (JAMA Oncol. (2023) 9: 5) (675-682) DOI: 10.1001/jamaoncol.2022.7966."  9(8): 1155.
	The Original Investigation titled "Efficacy and SafetyofWeeklyPaclitaxel Plus Vistusertib vsPaclitaxel Alone inPatients With Platinum‐Resistant Ovarian High‐Grade Serous Carcinoma: The OCTOPUS Multicenter, Phase 2, Randomized Clinical Trial,"1 published online March 16, 2023, in the May 2023 print issue, has changed license status to open access (CC‐BYNC‐ND license). This article has been updated online.

(2023). "Evaluation of the Efficacy of HIFU Treatment on Rectal Endometriosis Symptoms." https://clinicaltrials.gov/show/NCT05755958.
	Rectal endometriosis (RE) induces lesions associated with painful symptoms that can alter quality of life. High Intensity Focused Ultrasound (HIFU) is a non‐invasive ablative procedure using a high‐intensity ultrasound probe to induce tissue devitalization using acoustic cavitation and thermal ablation. Focal One® is a transrectal HIFU device, which is validated to treat prostatic cancer. In this comparative, randomized, double blind study , the primary objective is to evaluate the efficacy of the HIFU treatment of rectal endometriosis with Focal One® HIFU device on the Acute Pelvic Pain 3 months after HIFU treatment, in comparison to a Sham group.

(2023). "Expression of concern: "Calcium plus vitamin D supplementation influences biomarkers of inflammation and oxidative stress in overweight and vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial"." Clinical Endocrinology 98(5): 746.
	
(2023). "Expression of concern: oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial and The effects of coenzyme Q10 supplementation on gene expression related to insulin, lipid and inflammation in patients with polycystic ovary syndrome." Gynecological Endocrinology 39(1): 1841983.
	
(2023). "Fezolinetant (Veozah) for menopausal vasomotor symptoms." The Medical letter on drugs and therapeutics 65(1679): 97-99.
	
(2023). "ICI-Chemo New Standard for Endometrial Cancer." Cancer discovery 13(5): 1030-1031.
	The phase III RUBY and NRG-GY018 trials indicate that women with advanced endometrial cancer whose disease is newly diagnosed or has recurred for the first time benefit from the combination of a PD-1 inhibitor with standard chemotherapy. Adding either dostarlimab or pembrolizumab significantly prolonged progression-free survival, with overall survival also trending in the right direction. (©2023 American Association for Cancer Research.)

(2023). "In brief: A new endometrial cancer indication for dostarlimab (Jemperli)." The Medical letter on drugs and therapeutics 65(1683): e138.
	
(2023). "Incorrect Interquartile Ranges." JAMA 330(12): 1194.
	The Original Investigation titled "Operative Hysteroscopy vs Vacuum Aspiration for Incomplete Spontaneous Abortion: A Randomized Clinical Trial,"1 published on April 11, 2023, was corrected to fix incorrect IQR values in Table 1. The median IQR for gravidity in the hysteroscopy and vacuum aspiration groups should have been reported as "2 (2‐4)."The median IQR for parity in the hysteroscopy and vacuum aspiration groups should have been reported as "1 (0‐2)."This article was corrected online.

(2023). "Management of Premenstrual Disorders: ACOG Clinical Practice Guideline No. 7." Obstetrics and Gynecology 142(6): 1516-1533.
	Purpose: To provide recommendations for the management of premenstrual syndrome and premenstrual dysphoric disorder, collectively referred to as premenstrual disorders, based on assessment of the evidence regarding the safety and efficacy of available treatment options. An overview of the epidemiology, pathophysiology, and diagnosis of premenstrual disorders also is included to provide readers with relevant background information and context for the clinical recommendations.; Target Population: Reproductive-aged adults and adolescents with premenstrual symptoms.; Methods: This guideline was developed using an a priori protocol in conjunction with a writing team consisting of two specialists in obstetrics and gynecology appointed by the ACOG Committee on Clinical Practice Guidelines-Gynecology and one external subject matter expert. ACOG medical librarians completed a comprehensive literature search for primary literature within Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development and Evaluations) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements.; Recommendations: This Clinical Practice Guideline includes recommendations on the following evidence-based treatment options for premenstrual disorders, with an acknowledgement that many patients may benefit from a multimodal approach that combines several interventions: pharmacologic agents (hormonal and nonhormonal), psychological counseling, complementary and alternative treatments, exercise and nutritional therapies, patient education and self-help strategies, and surgical management. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence. Based on review of extrapolated data from adult populations and expert consensus, it was determined that the recommendations also apply to adolescents, with a few exceptions that are noted in the Clinical Practice Guideline. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

(2023). "Managing Outpatient Hysteroscopy-associated Pain." https://clinicaltrials.gov/show/NCT05801172.
	A prospective randomized trial (consent no.1072.6120.228.2021) includes women subjected to OH due to focal uterine lesion, abnormal uterine bleeding, or infertility. Women are randomly assigned to 3 arms ‐ A: NSAID (ketoprofen 100 mg intravenously), B: A+infiltration anesthesia (20 ml 1% lidocaine), C: A+paracervical block (20 ml 1% lidocaine). Karl Storz 5.0 mm Bettocchi® operative sheath with 2.9 mm 30 degree telescope and 5 Fr working channel was used. Intensity of pain in numeric rating scale (NRS), intensity of cervical bleeding, frequency of vaso‐vagal reaction, and frequency of abandoning/ limiting the procedure were compared.

(2023). "Maternal Well-being in the Postnatal Stage."
	The objective of this study is to design and validate an online intervention aimed at promoting well‐being in women with postpartum depression. For this, the design of a multicomponent protocol consisting of empirically validated positive interventions and comparing these with a group Cognitive Behavioral Therapy (CBT) is proposed, following the National Institute for Health and Care Excellence (NICE) recommendations for the treatment of depression. Participants will be screened for inclusion in the program if they meet clinical criteria. After that, they will be randomly assigned to a CBT group or a positive psychology intervention group.

(2023). "Online Brief CBT Intervention for Women With PCOS." https://clinicaltrials.gov/show/NCT05679362.
	The online brief CBT intervention is designed to address three problems that have often been reported in women with PCOS. Therefore, the program contains three themes: Psychoeducation about PCOS; traditional CBT and problem‐solving therapy. The brief CBT intervention consists of 5 online individual CBT sessions (60 minutes per session) or 5 group CBT sessions (60 minutes per session). Participants are randomized into one of three groups: 1. immediate individual treatment (A) 2. immediate group treatment (B) and 3. a wait‐list‐control group. The immediately treatment A and B begins for a total duration of 3 months: Week 1: Session 1 +homework assignments Week 3: Session 2 +homework assignments Week 5: Session 3 +homework assignments Week 8: Session 4 +homework assignments Week 12: Session 5 +homework assignments The wait‐list control group receives no treatment for the first three months, at which point they will cross over to one of the intervention arms (individual treatment A or group treatment B) and start with the intervention.

(2023). "Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial." Clinical Endocrinology 98(5): 745.
	
(2023). "Oral versus vaginal progestogens in women with recurrent miscarriages." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20230117057148N1.
	INTERVENTION: Intervention 1: Interventional Group 1: This group will be given oral progestogens in a dose of 10mg twice a day in morning and evening after meals for 12 weeks. Efficacy will be measured by continuation of pregnancy beyond 12 weeks. All the data will be recorded in predesigned data. Transvaginal ultrasound will be performed at 7, 9 and 12 week of gestation. Ultrasonography will be looked for presence of fetal cardiac activity. This group will also serve as control as it is the standard routine route by which progestogens are given. Intervention 2: Intervention group 2: This group was prescribed vaginal progestogens in a dose of 200mg twice a day for 12 weeks. Efficacy was measured by continuation of pregnancy beyond 12 weeks. All the data will be recorded in predesigned data. Transvaginal ultrasound will performed at 7, 9 and 12 week of gestation. Ultrasonography will be looked for presence of fetal cardiac activity. CONDITION: recurrent miscarriages. ; Spontaneous abortion PRIMARY OUTCOME: Pregnancy. Timepoint: 12 weeks of gestation. Method of measurement: ultrasound. INCLUSION CRITERIA: Pregnancy Aged 16‐40 years, A history of at least three recurrent miscarriages At or less than 7 weeks of gestational age

(2023). "ovary cyst and exercises." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/01/048652.
	INTERVENTION: Intervention1: Functional Resisted exercises,diet: Blood pressure and heart rate will be recorded at the beginning of each session, followed by 5‐minute warm up that consisted of marching in place, unilateral reaches(unweighted), and side‐step lunges (unweighted). The warm‐up will be followed by the exercise protocol. â?¢ The exercises which will be performed, in order, squats, wood chopping, side step squat, bent row, reverse lunge with rotation, triceps dip, deadlift, modified pushups and chest raises. GROUP A â?¢ Each of the exercises require subjects to begin in a standing position with feet approximately shoulder width apart, and each exercise will perform with a focus on accuracy and form.The resistance of 40 to 60% of 1RM will be chosen for training. â?¢ Subjects will be given 90 seconds of rest between each set. At the beginning of the study, each subject will perform 2 sets of 5‐8 repetitions. â?¢ From that point on, the volume (sets and repetitions) will increase for each exercise biweekly. â?¢ At week 3 subjects will be asked to perform exercises 3 sets of 7 repetitions; at week 5 subjects will be asked to perform 4 sets of 7 repetitions, and finally at week 6 subjects will be asked to perform 4 sets of 9‐10 repetitions. Control Intervention1: Aerobics&Diet: Blood pressure and heart rate will be recorded at the beginning of each session, followed by 5‐minute warm up that consisted of Jumping jacks(15 reps),High knees(15 reps),Butt kicks(15 reps),Lunges(15 reps) The warm‐up will be Followed by the exercise protocol. Moderate‐intensity continuous training (MICT): 40 min of walking/jogging on the treadmill at 70â??80% HR max Cool down by slowing down the speed of treadmill for 5 minutes CONDITION: Health Condition 1: E282‐ Polycystic ovarian syndrome PRIMARY OUTCOME: Fasting blood glucose levels ; 2.Fasting Insulin ; 3.HOMA IR index ; 4. The Polycystic Ovary Syndrome Quality of Life scaleTimepoint: ; one at the start of study and other after SECONDARY OUTCOME: The Polycystic Ovary Syndrome Quality of Life scaleTimepoint: one at the start of study and other after exercise intervention INCLUSION CRITERIA: 1. Diagnosed cases of PCOS 2. Age‐19‐35 years 3. BMI‐25‐35 kg/m2

(2023). "Palliative pharmacotherapy for cancer-related fatigue." https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20150302021307N6.
	INTERVENTION: Intervention 1: First intervention group: They will receive oral methylphenidate for 4 weeks. Methylphenidate is started at a dose of 5 mg per day in the first week. After that, the dose of 5 mg twice a day is continued in the second and third week. After that, in the fourth week, the dose returns to 5 mg per day. Intervention 2: Second intervention group: They will receive oral bupropion for 4 weeks. Bupropion is started at a dose of 150 mg per day in the first week. After that, the dose of 150 mg twice a day is continued in the second and third week. After that, in the fourth week, the dose returns to 150 mg per day. Intervention 3: Third intervention group: They will receive oral amantadine for 4 weeks. Amantadine is started at a dose of 100 mg per day in the first week. After that, the dose of 100 mg twice a day is continued in the second and third week. After that, in the fourth week, the dose returns to 100 mg per day. Intervention 4: Fourth intervention group: They will receive oral ginseng for 4 weeks. Ginseng is started at a dose of 500 mg per day in the first week. After that, the dose of 500 mg twice a day is continued in the second and third week. After that, in the fourth week, the dose returns to 500 mg per day. Intervention 5: Control group: They will receive oral placebo. Placebo will start one capsule daily in the first week. After that, two capsules per day will continue in the second and third week. After that, one capsule will be consumed again in the fourth week. CONDITION: Cancer‐related fatigue. ; Malaise and fatigue PRIMARY OUTCOME: Fatigue level over time, which will be measured by the functional assessment of chronic illness therapy‐fatigue scale. Timepoint: Fatigue level will be measured at baseline, weekly during the 4‐week intervention period, and sixth and eighth weeks as follow‐up. Totally, fatigue level will be measured for 7 times. Method of measurement: The functional assessment of chronic illness therapy‐fatigue scale. SECONDARY OUTCOME: To evaluate the safety, the secondary outcome is the adverse events, which will be assessed by the Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events. (Adverse events will be evaluated in 14 subgroups including oral, respiratory, neurological, sleep, sexual, cardio, visual, mood, cutaneous, gastrointestinal, attention, pain, genitourinary, and miscellaneous). Timepoint: Adverse events will be assessed at baseline, and weekly during the 4‐week intervention period. Method of measurement: The Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events. INCLUSION CRITERIA: Age over 18 years with advanced cancer diagnosis undergoing active anticancer treatment Participants with all types of cancer except patients with central nervous system tumor or hormone‐sensitive cancers or Pheochromocytoma Report of moderate to severe fatigue in the last week (score = 4 on a scale of 0 to 10) Diagnosis of cancer‐related fatigue based on International Classification of Diseases 10th edition (ICD‐10) criteria Hemoglobin level above 9 g/dL in 2 weeks before enrollment Ability to swallow and absorb medications Females who are likely to become pregnant should use contraceptive methods during treatment and up to 6 weeks after. Ability to read and write

(2023). "Pelvic Floor Physical Therapy vs Standard Care in Transgender Women Undergoing Vaginoplasty for Gender Affirmation."
	This was a randomized double‐blind study. Both subjects and the surgeon performing the surgery as well as the personnel administering questionnaires to patients postoperatively were blinded to the randomization. Recruitment, Enrollment and Randomization Patients scheduled to undergo vaginoplasty surgery at Cleveland Clinic Main campus were approached about voluntary participation in this study. This occurred over the phone approximately one to three months before their scheduled surgery. Patients who agreed to participate were sent a consent form via the mail and were asked to sign consent in person. Enrollment and randomization occurred following informed consent. All patients were given a copy of their signed and dated consent. Once enrolled, patients were randomized into one of two groups: ‐ Postoperative PFPT ‐ No Postoperative PFPT If patients were randomized into the Postoperative PFPT arm, they were further randomized into the following sub‐arms: ‐ Postoperative PFPT alone ‐ Preoperative and Postoperative PFPT Surgery: All patients underwent vaginoplasty surgery by a single surgeon in a standard fashion. The neovaginal cavity was created using the same technique across all patients. Postoperative care was routine and the same for all patients. Postoperative Pelvic Floor Physical Therapy: There was three possible PFPT regimens. All PT regimens were performed by the same two physical therapists, trained in the management of patients who have undergone vaginoplasty surgery. 1. No PFPT Patients were present to see the physical therapist 3 weeks postoperatively. The following interventions were performed: Subjective assessment of bowel and bladder function. Visual and external palpation and assessment of external pelvic floor region. Intravaginal pelvic floor assessment. Pelvic floor muscle dynamics and coordination assessment. Review of pelvic floor anatomy and function. 2. Postoperative PFPT Only Patients presented to the physical therapist 3 weeks and 6 weeks postoperatively. The following interventions were performed: 3 weeks: ‐ Subjective assessment of bowel and bladder function ‐ Visual and external palpation and assessment of external pelvic floor region ‐ Intravaginal pelvic floor assessment ‐ Pelvic floor muscle dynamics and coordination assessment ‐ Instruction of pelvic floor coordination and lengthening ‐ Discussion of dilator program and progression ‐ Home program with instructions 6 weeks: ‐ External scar assessment and treatment if tissue healing allows ‐ Instruction to patient of scar mobilizations ‐ Intravaginal pelvic floor assessment and treatment if indicated ‐ Review of pelvic floor lengthening and coordination ‐ Review and progression of dilator program if appropriate ‐ Assessment of current bowel/bladder symptoms; home program and instructions to address these symptoms 3) Preoperative PFPT and Postoperative PFPT: Patients presented to see the physical therapist 3 weeks before surgery, 3 weeks and 6 weeks postoperatively. The following interventions were performed: Preoperative: ‐ Diaphragmatic breathing ‐ Discuss dilator positioning/introduce dilator program ‐ External pelvic floor assessment ‐ Teach pelvic floor coordination ‐ Assessment of current bowel/bladder symptoms; home program and instructions to address these symptoms 3 weeks: ‐ Subjective assessment of bowel and bladder function ‐ Visual and external palpation and assessment of external pelvic floor region ‐ Intravaginal pelvic floor assessment ‐ Pelvic floor muscle dynamics and coordination assessment ‐ Instruction of pelvic floor coordination and lengthening ‐ Discussion of dilator program and progression ‐ Home program with instructions 6 weeks: ‐ External scar assessment and treatment if tissue healing allows ‐ Instruction to patient of scar mobilizations ‐ Intravaginal pelvic floor assessment and treatment if indicated ‐ Review of pelvic floor lengthening and coordination ‐ Review and progression of dilator program if appropriate ‐ Assessment of curren bowel/bladder symptoms; home program and instructions to address these symptoms Study Questionnaires & Exams: All patients were administered questionnaires preoperatively and 12 weeks postoperatively. The following questionnaires were administered: Preoperatively: ‐ CRAD‐8 and UDI‐6 ‐ PFIQ‐7 Postoperatively 1 week (at the time of routine dilation teaching): • Vaginal length (routine exam) Postoperatively 12 weeks: ‐ CRAD‐8 and UDI‐6 ‐ PFIQ‐7 ‐ PGI‐I ‐ Ease of Passing Dilator (VAS 0‐10) ‐ Pain with Dilation (VAS 0‐10) ‐ Largest dilator size used ‐ Vaginal length (routine exam) Cross‐Over Treatment: Any patients in the No PFPT arm who were determined to have pelvic floor dysfunction or symptoms that may have benefitted from PFPT referral, were referred after the 12‐week mark. Any patient in one of the PFPT arms who was determined to still need PFPT for persistent pelvic floor dysfunction or symptoms were referred for continued care.

(2023). "Platelet Rich Plasma as an Adjunct Therapy at the Time of Transvaginal Native Tissue Prolapse Surgery." https://clinicaltrials.gov/show/NCT05731284.
	Platelet rich plasma (PRP) is an autologous product with high levels of platelets which are concentrated with bioactive growth factors responsible for accelerating tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis and neurogenesis. The overarching goal is to evaluate the effectiveness and safety of the adjunct application of PRP in the fibromuscular connective tissue (the site of anterior tissue plication) at the time of anterior colporrhaphy (the site of highest recurrence risk) in women undergoing native tissue vaginal prolapse repair, to promote tissue healing and regeneration, thus to improve surgical outcomes.

(2023). "POSTCARE-O: SURVIVORSHIP CARE FOR WOMEN LIVING WITH OVARIAN CANCER." https://clinicaltrials.gov/show/NCT05752448.
	Study Design We will conduct a 2‐arm randomized controlled trial to evaluate the impact of a telehealth delivered survivorship transition care process. Ovarian cancer survivors (120) will be randomly allocated to receive survivorship care either using the POSTCare Process or standard of care. Study design and reporting will be in accordance with the Consolidated Standards of Reporting Trials (CONSORT) checklist. We will use quantitative and qualitative methodologies in a concurrent triangulation mixed methods design utilizing qualitative data to augment our interpretation of quantitative data. Outcomes will be collected at baseline, 12 weeks and 24 weeks, with the primary outcome being quality of life assessment at 12 weeks. Sample Size We will enroll 120 women completing primary treatment for Stage 2‐4 ovarian cancer from 3 urban gynecologic oncology clinics located in the Southern United States. Participants will have received some combination of surgery, chemotherapy, radiation therapy, and biologics. Continued maintenance therapy is not an exclusion factor. Aim 1 proposes to implement a randomized controlled trial (RCT) devised to compare QOL measures among ovarian cancer patient randomized to receive usual care versus the POSTCare survivorship care transition program. The Functional Assessment of Cancer Therapy‐Ovarian (FACT‐O) QOL survey will be collected at baseline as well as 12 and 24 weeks after the initial course of adjuvant chemotherapy. The primary endpoint will be the 12‐week survey. We expect to observe a mean 12‐week FACT‐O score of 116 with standard deviation of 20 for women receiving usual care. The sample size of N=120 patients provides at least 80% power to detect a 7% increase in the mean FACT‐O score for women randomized to the POSTCare survivorship care intervention. This is sufficient to ascertain a minimally important difference of 8 points. Recruitment and Setting We will recruit participants from Gynecologic Oncology practices at 3 clinic settings in Texas: One safety net practice located in Dallas, one safety net practice located in Houston, and one faculty group practice located in Houston. Cumulatively the sites serve approximately 120 eligible patients per year and ensure a diverse population can be recruited during the 24‐month recruitment period. 120 women will be recruited. Sixty participants will be randomly assigned to the intervention group and receive care using the POSTCare Process and 60 will be randomly assigned to the control group. It is anticipated that our study sample will reflect the ethnic and racial diversity of our clinical settings.

(2023). "Preliminary outcomes of modified posterior colporrhaphy." https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300067337.
	INTERVENTION: Group 1:Modified posterior colporrhaphy;Group 2:None; CONDITION: Vaginal relaxation combined with urinary stress incontinence PRIMARY OUTCOME: Female sexual function index, FSFI;Vaginal laxity questionnaire, VLQ;Incontinence Quality of life Questionnaires, I‐QOL; INCLUSION CRITERIA: 1. Patients with urinary incontinence were confirmed to have loose vagina by gynecological examination before surgery; 2. Patients with indications for vaginoplasty; 3. Patients who signed the informed consent form before the operation; 4. Patients with complete clinical data preservation.

(2023). "A prospective randomized controlled study on the relationship between preserving/removing circumflex iliac lymph nodes and lower limb lymphedema following lymphadenectomy in gynecological malignancies."
	INTERVENTION: Group one:pelvic lymphadenectomy with circumfle Xiliac nodes distal to the external iliac node (CINDEIN) preservation;Group two:pelvic lymphadenectomy with circumfle Xiliac nodes distal to the external iliac node (CINDEIN) removal; CONDITION: gynecologic oncology PRIMARY OUTCOME: the incidence of Lower limb lymphedema; SECONDARY OUTCOME: the metastasis rate of circumfle Xiliac nodes; INCLUSION CRITERIA: (1) Stages ? b1 ? A2 cervical cancer, ? ? uterine malignant tumors, and various stages of ovarian malignant tumors undergoing satisfactory ovarian tumor cell reduction surgery with clear pathological diagnosis (FIGO 2009 staging); (2) Age 18‐75 years old; (3) Willing to undergo surgery without any contraindications; (4) All patient surgeries include pelvic lymph node dissection; (5) Enrolled patients must understand and voluntarily participate in the study, and sign an informed consent form.

(2023). "A randomized controlled study on acupuncture treatment of levator ani syndrome."
	INTERVENTION: Acupuncture group:After communicating with the patient, the patient was instructed to take the prone position and the local skin was routinely disinfected. The acupuncturist acupunctured the patient 's bilateral Zhongliao ( sacrum, right in the third sacral foramen ) and Xialiao ( sacrum, right in the fourth sacral foramen ). Operation : 3‐inch filiform needle ( 0.35 * 0.75mm ) was punctured into the posterior sacral foramen, obliquely punctured 75mm, the tip of the needle was in the direction of the inner side and the root of the thigh. The needle body was 30 o angle with the longitudinal axis of the human body and 60 o angle with the skin. After acupuncture, the needle was gently lifted, inserted and twisted to obtain qi. After obtaining qi, the needle sensation was radiated to the anus. Bilateral Zhongliao and Xialiao points were connected with electroacupuncture at a frequency of 2 / 15 Hz and a stimulation intensity of 1 5 mA, which was based on patient comfort. Retain the needle for 30 minutes, no needle during the needle retention process.;sham acupuncture group:After communicating with the patient, the patient was instructed to take the prone position and the local skin was routinely disinfected. The acupuncturist took the bilateral false Zhongliao point to open 20 mm outward at the bilateral Zhenzhongliao point, the bilateral false Xialiao point to open 20 mm outward at the bilateral Zhenxialiao point, and the shallow acupuncture was 3‐5 mm. The electroacupuncture electrode placement and parameter setting were the same as those in the acupuncture group. Acupuncture had no operation of deqi, and electroacupuncture had no output. Retain the needle for 30 minutes, no needle during the needle retention process.; CONDITION: levator ani syndrome PRIMARY OUTCOME: Clinical treatment efficiency; SECONDARY OUTCOME: Pain days per month;life quality evaluation;psychological assessment;anorectal manometry;Pelvic floor surface electromyography detection;tcm syndrome score; INCLUSION CRITERIA: Subjects must meet all the following requirements : ( 1 ) Patients who met the diagnostic criteria for levator ani syndrome ( functional gastrointestinal disease Rome IV ) ; ( 2 ) Patients with chronic or recurrent anorectal pain, each pain lasted at least 30 minutes, at least once a week, symptoms appear = 1 year, rectal examination : puborectalis traction pain ; ( 3 ) Age 20 to 70 years old, gender is not limited ; ( 4 ) Those who did not receive acupuncture treatment 3 months before enrollment ; ( 5 ) Participants voluntarily participated and signed informed consent

(2023). "Robotic-Assisted Hysterectomy for Endometrial Cancer in People With Obesity: A Health Technology Assessment." Ontario Health Technology Assessment Series 23(6): 1-70.
	Background: Robotic-assisted surgery has been used in Ontario hospitals for over a decade, but there is no public funding for the robotic systems or the disposables required to perform robotic-assisted surgeries ("robotics disposables"). We conducted a health technology assessment of robotic-assisted hysterectomy (RH) for the treatment of endometrial cancer in people with obesity. Our assessment included an evaluation of the effectiveness, safety, and cost-effectiveness of RH, as well as the 5-year budget impact for the Ontario Ministry of Health of publicly funding RH. It also looked at the experiences, preferences, and values of people with endometrial cancer and obesity, as well as those of health care professionals who provide surgical treatment for endometrial cancer.; Methods: We performed a systematic literature search of the clinical evidence to identify systematic reviews and randomized controlled trials relevant to our research question. We reported the risk of bias from the included systematic review. We assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search. We also analyzed the 5-year budget impact of publicly funding RH (including total, partial, and radical procedures) for people with endometrial cancer and obesity in Ontario. To contextualize the potential value of RH for people with endometrial cancer and obesity, we spoke with people with lived experience of endometrial cancer and obesity who had undergone minimally invasive surgery (either laparoscopic hysterectomy [LH] or RH), and we spoke with gynecological cancer surgeons who perform hysterectomy.; Results: We included one systematic review in the clinical evidence review. An indirect comparison showed that conversion rates to open hysterectomy (OH) were similar for LH and RH in patients with a body mass index (BMI) ≥ 30 kg/m 2 (6.5% vs. 5.5%, respectively) (GRADE: Very low). An indirect comparison within a subset of patients with a body mass index (BMI) ≥ 40 kg/m 2 showed that a higher proportion of patients who underwent LH required conversion to OH compared with patients who underwent RH (7.0% vs. 3.8%, respectively) (GRADE: Very low). Rates of perioperative complications were similarly low for both LH and RH (≤ 3.5%) (GRADE: Very low). We identified two studies that met the inclusion criteria of our economic literature review. The included economic studies found RH to be more costly than OH or LH for endometrial cancer; however, because these studies were conducted in other countries, the results were not applicable to the Ontario context. Assuming a moderate increase in the volume of robotic-assisted surgeries, our reference case analysis showed that the 5-year budget impact of publicly funding RH for people with endometrial cancer and obesity would be $1.14 million. The budget impact analysis results were sensitive to surgical volume and the cost of robotics disposables. The people we spoke with who had lived experience of endometrial cancer and obesity, as well as gynecological cancer surgeons, spoke favourably of RH and its perceived benefits over OH and LH for people with endometrial cancer and obesity.; Conclusions: Compared with LH, RH is associated with fewer conversions to OH in patients with endometrial cancer and obesity (i.e., those with a BMI ≥ 40 kg/m 2 ). Rates of perioperative complications were similarly low for both LH and RH. The cost-effectiveness of RH for people with endometrial cancer and obesity is unknown. We estimate that the 5-year budget impact of publicly funding RH for people with endometrial cancer and obesity would be $1.14 million. People we spoke with who had lived experience of endometrial cancer and obesity reported favourably on their experiences with minimally invasive hysterectomy (either LH or RH) and emphasized the importance of the availability of safe surgical options for people with obesity. Gynecological surgeons perceived RH as a perior alternative to OH and LH for people with endometrial cancer and obesity. (Copyright © Queen's Printer for Ontario, 2023.)

(2023). "Study of ART0380 in Advanced/Metastatic Solid Tumors Patients."
	ART0380 is being developed as an oral anti‐cancer agent for the treatment of patients with cancers that have defects in deoxyribonucleic acid (DNA) repair. The study will recruit selected patients with advanced or metastatic solid tumors, specifically: ‐ Patients with persistent or recurrent endometrial cancer (EC) ‐ Patients with advanced or metastatic solid tumors of any histology Above patients will be randomized in a 1:1 ratio to one of two dose regimens of ART0380. Safety will be evaluated on a quarterly basis, at a minimum. Patients may continue to receive ART0380 as long as they are continuing to derive benefit from treatment or until disease progression, withdrawal of consent, or until they experience unacceptable drug‐related toxicity.

(2023). "The Study on the Therapeutic Effect and Mechanism of Transcutaneous Acupoint Electrical Stimulation in Female." https://clinicaltrials.gov/show/NCT05799924.
	Dysmenorrhea is a common female disease, with an incidence about 20‐40% in female, affecting the living quality of the patients. The treatment of dysmenorrhea usually includes hormone drugs to suppress ovulation, and oral non‐steroidal anti‐inflammatory drugs to relieve pain, but symptoms would relapse after drugs withdrawal. While long‐term use of these drugs may cause endocrine disorders, even affect the normal preparation of pregnancy. Recent studies have shown that dysmenorrhea is related to many factors such as immune and neuroendocrine changes. Transcutaneous electric acupoint stimulation (TEAS) is a new therapeutic method derived from traditional acupuncture therapy. In this method, the electrode placed on the surface of the skin of acupoints is used to guide the stimulating current into the body and stimulate the acupoints to achieve the goal of treatment, and can effectively relieve the pain of patients by replacing the traditional mechanical stimulation of hand‐twisting needles. The aim of this study is to treat dysmenorrhea in women with TEAS, and to observe the therapeutic effect of TEAS, at the same time, prostaglandins, pain‐related factors and immune‐related factors were detected in dysmenorrhea women before and after treatment to study the mechanism.

(2023). "Therapeutic Exercise and Education in Neurophysiology of Pain in the Quality of Life of Women With Endometriosis."
	A study will be carried out whose objective is to improve the quality of life in women with endometriosis through a program of therapeutic exercise and education in the neurophysiology of pain. Also as secondary variables will be observed: menstrual symptoms, sexual function, and abdominal wall thickness measured with ultrasound.

(2023). "THERAPEUTIC EXERCISE AND EDUCATION IN PAIN NEUROPHYSIOLOGY TO IMPROVE PAIN INTENSITY IN WOMEN WITH ENDOMETRIOSIS. CLINICAL TRIAL."
	A study will be carried out whose objective is to improve the intensity of pain in women with endometriosis through a program of therapeutic exercise and education in the neurophysiology of pain. Also as secondary variables will be observed: kinesiophobia, catastrophism and impression of global improvement with treatment.

(2023). "This is a Bioequivalence Study between formulations of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (50 mg/m2 dose) for treating Patients with Advanced Ovarian Cancer." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/03/050946.
	INTERVENTION: Intervention1: Doxorubicin Hydrochloride Liposome Injection: Dose Formulation‐Liposomal formulation,Dosage Level(s) 50 mg/m2,Route of Administration ‐Intravenous Control Intervention1: Doxorubicin Hydrochloride Liposome Injection: Dose Formulation‐Liposomal formulation,Dosage Level(s) 50 mg/m2,Route of Administration ‐Intravenous CONDITION: Health Condition 1: C569‐ Malignant neoplasm of unspecifiedovary PRIMARY OUTCOME: To characterize the pharmacokinetic profile and to assess the bioequivalence of Doxorubicin‐Test relative to Doxorubicin‐Reference in participants with advanced ovarian cancer.Timepoint: Pre‐dose (0.000), 0.333, 0.667, 1.250, 1.500, 2.000, 2.500, 3.000, 5.000, 8.000, 12.000, 16.000, 24.000, 48.000, 72.000, 120.000, 168.000, 216.000, 264.000, 312.000 and 360.000 hours. SECONDARY OUTCOME: To further characterize the pharmacokinetic profile of Doxorubicin‐Test relative to Doxorubicin‐Reference in participants with advanced ovarian cancerTimepoint: Pre‐dose (0.000), 0.333, 0.667, 1.250, 1.500, 2.000, 2.500, 3.000, 5.000, 8.000, 12.000, 16.000, 24.000, 48.000, 72.000, 120.000, 168.000, 216.000, 264.000, 312.000 and 360.000 hours. INCLUSION CRITERIA: 1 Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study as described in Appendi X10.1.3 and in this protocol and is willing to participate in the study.2 Female participant must be 18 to 75 years of age (both inclusive), at the time of signing the informed consent.3 Participant with documented advanced ovarian cancer whose disease has progressed or recurred after platinum‐based chemotherapy AND who are already receiving or scheduled to start the monotherapy.4 Life expectancy of more than or equal to 12 weeks at screening visit.5 An Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 at screening visit.6 Participant should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator. Participants who are already receiving doxorubicin hydrochloride liposome injection at a dose of 50 mg/m2 should not require dose reduction(s) in next planned

(2023). ""To Assess The Improvement In Cases of Polycystic Ovarian Syndrome After Constitutional Homeopathic Treatment Through Homeopathic Medical Repertory."." https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2023/02/049369.
	INTERVENTION: Intervention1: Homoeopathic Constitutional Similimum: Potentised Homeopathic medicine in the form of pills. Dose:The final selected remedy based on the individual totality will be prescribed in appropriate (200 C) potency and doses based on the susceptibility of individual case. Route of Administration‐ Oral Control Intervention1: Placebo: Placebo is given in the form of pills. CONDITION: Health Condition 1: E282‐ Polycystic ovarian syndrome PRIMARY OUTCOME: To evaluate effectiveness of individualized Homeopathic medicines in treatment of cases of polycystic ovarian syndromeTimepoint: Clinical examination ie effect on BMI, Hirsutism, Acne and appropriate investigations such as Hormonal assay FSH LH ratio androgen levels,USG reports, Ferriman gallwey score, Acne global severity scale score after 12 months treatment SECONDARY OUTCOME: 1.To ascertain adequacy of specific rubrics related to Polycystic Ovarian Syndrome from Homeopathic Medical Repertory 2. To assess the improvement in health related quality of life (HRQoL) in women suffering with Polycystic Ovarian SyndromeTimepoint: PCOSQ score before and after treatment for period of 12 months INCLUSION CRITERIA: 1.Female cases diagnosed with PCOS using Rotterdam criteria 2. Womens age group 12‐40 years are included in my study 3. Patients giving written consent and voluntarily participate in study

(2023). "Trauma-informed Approach to Timely Detection and Management of Early Postpartum Hypertension."
	This study will compare two interventions with the standard of care. Given that this is a stepped‐wedge design, all sites will begin with recruitment for the standard of care. All study participants will be identified, recruited and enrolled during their postpartum hospital stay (i.e. prior to discharge) by research study staff. Once study participants are enrolled, they will receive a Omron blood pressure (BP) cuff and will be instructed on how to use it. General Design Description Overall study design. This project spans three states (Connecticut, Massachusetts, New York) and includes three hospitals (Yale New Haven Hospital, UMass Worcester, and Oishei in Buffalo, New York). This is a multisite intervention study that follows a sequential stepped‐wedge design with the 3 hospitals randomized to their start time for the first arm followed by the second and third arms. Yale will serve as the coordinating center and facilitate as well as oversee the planning and implementation activities across sites to ensure standardization. All study staff at all centers will undergo training sessions in blood pressure measurement and management following a standardized protocol as well as mental health screening and management and refresher training sessions, as needed, including any remedial training in specific areas targeted by quality control monitoring for a specific site. Yale New Haven Hospital will provide the appropriate assistance across clinical sites. This may include site visits, to ensure that the study enrollment and treatment follows proper study procedures. Community Advisory Boards (CABs) will be formed at each of the project sites to integrate community perspectives into project activities and ensure community engagement in the decision‐making process throughout the duration of the project. The Yale Griffin Prevention Research Center (PRC) and Cicatelli Associates, Inc. (CAI) will be deeply engaged advising on the establishment of the CABs across sites. Twice a year, the three CABs will convene virtually to receive an update about the overall project progress and share ideas about strengthening study design and implementation to ensure it reflects overall community needs and best interests. We will compensate members for their participation and transportation plus provide refreshments for in‐person meetings. During in‐person meetings of the individual site CABs, current COVID protocols recommended by the Centers for Disease Control will be followed to ensure meetings are safe and participants protected. This study will compare two interventions with the standard of care. Given that this is a stepped‐wedge design, all sites will begin with recruitment for the standard of care. All study participants will be identified, recruited and enrolled during their postpartum hospital stay (i.e. prior to discharge) by research study staff. Once study participants are enrolled, they will receive a Omron blood pressure (BP) cuff and will be instructed on how to use it. Participants in the first intervention RMM will be provided with an Omron blood pressure cuff and blood pressure data will be recorded. Participants will be contacted within 72 hours following discharge. Follow‐up telehealth visits will occur at least 1 time per week for the first 6 weeks and up to 12 weeks as needed. There may be a need for more visits for those with high blood pressure or elevated scores on validated mental health screeners, therefore advanced practice professionals (APPs) will coordinate with the individual site team Co‐Is to address and arrange for additional follow‐up visits with the appropriate providers as indicated. In addition to the RMM described above, the second intervention, the community health model (CHM), includes the incorporation of research community health workers(CHW)/doulas who will be identified at each site. The CHWs/doulas will receive extensive training to be able to provide postpartum hypertension support and how to engage individuals in mental health services using a strengths‐based trauma‐inf rmed approach. CHWs/doulas will be available to the families during the first 6 weeks (at least 1x per week) and then every other month or as needed. A hybrid approach will be used with CHWs/doulas visiting participants in‐person and virtual based on the participant's needs and preferences. All participants will complete assessments and a blood pressure at intake along with telephone follow‐up assessments at 6 weeks postpartum, 3 months and 6 months postpartum including a blood pressure check and mental health screen with EPDS and other study surveys at each time point. Electronic medical record data will be collected.

(2023). "Use of Fractional CO2 Laser Versus Erbium: YAG Laser for the Treatment of GSM in Patients Using Aromatase Inhibitors."
	The objective is to compare microablative fractional CO2 laser (CO2 laser) (SmartXide2 V2 LR, Monalisa Touch; DEKA, Florence, Italy) and non‐ablative photothermal Erbium:YAG laser (Er:YAG laser) (Fotona Smooth™ XS; Fotona, Ljubljana, Slovenia) ‐ with sham vaginal applications for treatment of vaginal dryness as the leading symptom in breast cancer patients with iatrogenic menopause and treated with an AI.

(2023). "Uterine Manipulator Versus no Uterine Manipulator in Endometrial Cancer Trial."
	Minimally invasive surgery is the recommended approach in endometrial cancer (EC) patients based on the results of two randomized controlled trials, given its advantages without compromised oncologic outcomes. The uterine manipulator is commonly used in benign and malignant pathologies to perform a laparoscopic or robotic hysterectomy. However, although regularly used, the uterine manipulator adoption in EC is a controversial technical aspect due to the raised concerns regarding the possible risk of disruption of the tumor mass, the spread of malignant cells, and seeding of the disease, particularly at the level of the vaginal cuff or spread of tumor cells, with increased risk of recurrence and death due to EC. On that basis, given that hysterectomy without a uterine manipulator is feasible, only a randomized controlled trial comparing oncologic outcomes in EC patients after use versus not use of the uterine manipulator will be able to provide high‐quality evidence to answer this critical question and allow or exclude the use of a uterine manipulator during minimally invasive hysterectomy for EC.

(2023). "Zuranolone shows rapid‐acting effects in women with postpartum depression." Brown University Psychopharmacology Update 34(11): 1-5.
	Zuranolone, at a dose of 50 mg/day, led to significant improvement in depressive symptoms relative to placebo at two weeks in women with postpartum depression, a Phase 3 trial has found. Study results were published online July 26, 2023, in the American Journal of Psychiatry. In early August, the Food and Drug Administration (FDA) approved zuranolone for the treatment of postpartum depression.

a s, S., et al. (2021). DCVAC/OvCa and Standard of Care (SoC) in Relapsed Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma.
	No Results Available Biological: DCVAC/OvCa|Biological: DCVAC/OvCa placebo Overall Survival(OS)|Progression-Free Survival (PFS)|Objective Response Rate|Time to Relapse|Duration of Response|Biological Progression-Free Survival|Safety Assessments: NCI CTCAE version 5.0 Female Phase 3 0 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment SOV09|VITALIA/ ENGOT-ov53 August 16, 2021

Aarshageetha, P., et al. (2023). "Role of Alternate Therapies to Improve the Quality of Life in Menopausal Women: A Systematic Review." Journal of mid-life health 14(3): 153-158.
	Middle aged women in majority undergoing menopausal symptoms are unaware of the physiological changes happening in their body, necessary lifestyle changes and alternate therapies to overcome the symptoms. All major electronic sources of relevant information were systematically searched and collected data were pooled under specific subheadings. From the reviewed papers, the awareness on symptoms and related complications of menopause in the middle aged women were consolidated. Studies helped to identify alternative therapies replacing or in parallel with the Hormone Replacement Therapy to overcome the menopausal symptoms. Reduced oestrogen and progesterone level causes physiological, psychological, and genitourinary symptoms. Prolonged consequences cause libido, osteoporosis, and cardio vascular diseases. Hypo-estrogenic status is well managed with alternative therapies including dietary intervention, acupuncture, aromatherapy, exercise, and yoga. Dietary interventions involving foods like Fennel, Soy, Black Cohash, St. John Wort, Red Clover and Date Pollen were found to be managing vasomotor symptoms and sexual dysfunction. Non-Hormonal and Non-Pharmacological impact behind acupuncture treatment was well accepted. Various studies proved inhaling and massaging with Lavender, Neroli oil, Fennel, Rose, and Geranium essential oils balance cortisol hormone and reduce stress and anxiety. Impact of yoga therapy on neurohormonal pathways reduce both psychological and physiological symptoms. Reviews summarizes various symptoms and complications during menopausal transition and alternate ways of better management with dietary intervention, yoga, exercise, aromatherapy, and acupuncture to improve the quality of menopausal women's life.; Competing Interests: There are no conflicts of interest. (Copyright: © 2023 Journal of Mid-life Health.)

Abaoglu, H., et al. (2024). "Combined mind-body intervention for premenstrual dysphoric disorder: A randomized controlled trial." Health Care for Women International: 1-21.
	In this study, we aimed to examine the effectiveness of relaxation training in women with PMDD through a randomized controlled design. Sixty-three women were recruited and randomized to relaxation training or control groups. The outcome measurements, administered at baseline and post-training, included the Premenstrual Symptoms Screening Tool (PSST), Hospital Anxiety and Depression Scale (HADS), Nottingham Health Profile (NHP), and Sheehan Disability Scale (SDS). The intervention group received 12 sessions of relaxation training, including progressive muscle relaxation and guided imagination. While there were significant differences within the group in the relaxation training group, no significant differences were found in the control group. Relaxation training had a positive effect on reducing premenstrual symptoms, anxiety, depression and disability and improving quality of life in women with PMDD. More research is necessary to recommend relaxation training as a primary and long-term treatment and to understand how it should be included in a comprehensive treatment plan.

Abbara, A., et al. (2023). "Endocrine Responses to Triptorelin in Healthy Women, Women With Polycystic Ovary Syndrome, and Women With Hypothalamic Amenorrhea." The Journal of Clinical Endocrinology and Metabolism 108(7): 1666-1675.
	Context: Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic ovary syndrome (PCOS) compared with healthy women or those with hypothalamic amenorrhea (HA).; Objective: We compared the gonadotropin response to triptorelin in healthy women, women with PCOS, or those with HA without ovarian stimulation, and in women with or without polycystic ovaries undergoing oocyte donation cycles after ovarian stimulation.; Methods: The change in serum gonadotropin levels was determined in (1) a prospective single-blinded placebo-controlled study to determine the endocrine profile of triptorelin (0.2 mg) or saline-placebo in healthy women, women with PCOS, and those with HA, without ovarian stimulation; and (2) a retrospective analysis from a dose-finding randomized controlled trial of triptorelin (0.2-0.4 mg) in oocyte donation cycles after ovarian stimulation.; Results: In Study 1, triptorelin induced an increase in serum luteinizing hormone (LH) of similar amplitude in all women (mean peak LH: healthy, 52.3; PCOS, 46.2; HA, 41.3 IU/L). The AUC of change in serum follicle-stimulating hormone (FSH) was attenuated in women with PCOS compared with healthy women and women with HA (median AUC of change in serum FSH: PCOS, 127.2; healthy, 253.8; HA, 326.7 IU.h/L; P = 0.0005). In Study 2, FSH levels 4 hours after triptorelin were reduced in women with at least one polycystic morphology ovary (n = 60) vs normal morphology ovaries (n = 91) (34.0 vs 42.3 IU/L; P = 0.0003). Serum anti-Müllerian hormone (AMH) was negatively associated with the increase in FSH after triptorelin, both with and without ovarian stimulation.; Conclusion: FSH response to triptorelin was attenuated in women with polycystic ovaries, both with and without ovarian stimulation, and was negatively related to AMH levels. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Abbara, A., et al. (2024). "Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals." Fertility and Sterility 121(1): 95-106.
	Background: Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 can induce oocyte maturation during in vitro fertilization treatment, including in women who are at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported. Objective(s): To determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (phase-2a trial). Design(s): Two randomized, placebo-controlled, parallel-group, dose-finding trials. Setting(s): Clinical trials unit. Patient(s): Healthy women aged 18-35 years, either without (phase-1; n = 24), or with ovarian stimulation (phase-2a; n = 75). Intervention(s): Phase-1: single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 mug) or placebo, (n = 6 per dose). Phase-2a: single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 mug; n = 16-17 per dose), triptorelin 0.2 mg (n = 5; active comparator), or placebo (n = 5). Main Outcome Measure(s): Phase-1: safety/tolerability; pharmacokinetics; and pharmacodynamics (luteinizing hormone [LH] and other reproductive hormones). Phase-2a: safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); and time to ovulation assessed by transvaginal ultrasound. Result(s): In both the trials, MVT-602 was safe and well tolerated across the entire dose range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours. In the phase-2a trial, LH concentrations increased dose dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3 mug MVT-602 and remained >15 IU/L for 33 hours. Time to ovulation after drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 mug), 88% (1 mug), 82% (0.3 mug), and 75% (0.1 mug), of women after MVT-602, 100% after triptorelin and 60% after placebo. Conclusion(s): MVT-602 induces LH concentrations of similar amplitude and duration as the physiological midcycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR. Clinical Trial Registration Number: EUDRA-CT: 2017-003812-38, 2018-001379-20.Copyright © 2023 The Authors

Abbas Ahmed, M., et al. (2020). "Higher clinical pregnancy rate with in-vitro fertilization versus intracytoplasmic sperm injection in treatment of non-male factor infertility: Systematic review and meta-analysis." Journal of Gynecology Obstetrics and Human Reproduction 49(6): 101706.
	Objective: To evaluate the evidence about in-vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI) for the treatment of non-male factor infertility.; Data Sources: Electronic databases searched using the following MeSH terms (Sperm Injection, Intracytoplasmic) AND (in Vitro Fertilisation) AND (Infertility).; Methods of Study Selection: All RCTs included infertile patients due to non-male factors underwent IVF or ICSI were considered for this meta-analysis. One-thousand twenty-two studies were identified of which 20 studies deemed eligible for this review.; Data Extraction: Three independent authors extracted the relevant data from included studies. The study outcomes were pooled in the form of relative risk (RR) and 95 % confidence interval (CI) using Mantel-Hansel method. The main outcome measures are the fertilization rate, the implantation rate, the clinical pregnancy rate (CPR), the total fertilization failure and the live birth rate.; Results: Regarding the fertilization rate, the pooled estimate did not favour either IVF or ICSI group (RR = 0.94; 95 %CI [0.82, 1.07]; p = 0.34). However, IVF significantly increased the CPR than ICSI (RR = 1.28, 95 %CI [1.11, 1.49]; p = 0.001). The overall effect estimate did not favor either of two groups regarding the implantation rate (RR = 1.25, 95 % CI [0.92, 1.68], p = 0.15). Similarly, no difference between both groups regarding the live birth rate (RR = 1.08, 95 % CI [0.79, 1.49]; p = 0.62).; Conclusions: No difference between ICSI and IVF regarding fertilization rate per oocytes, implantation rate and live birth rate in the treatment of non-male factor infertility, while IVF has significantly higher clinical pregnancy rate and higher risk of total fertilization failure.; Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest. (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Abbas Ahmed, M., et al. (2019). "Medications for pain relief in outpatient endometrial sampling or biopsy: a systematic review and network meta-analysis." Fertility and Sterility 112(1): 140.
	Objective: To determine the most effective analgesia for pain relief during the outpatient endometrial biopsy (OEB) or outpatient hysteroscopy with endometrial aspiration (EA).; Design: Systematic review and network meta-analysis of randomized controlled trials.; Setting: Not applicable.; Patient(s): Pre- or postmenopausal women undergoing OEB or outpatient hysteroscopy with EA for evaluation of uterine pathology.; Intervention(s): We conducted an electronic search of the following bibliographic databases: Medline via PubMed, SCOPUS, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL).; Main Outcome Measure(s): The intensity of pain during, immediately after, and 10-30 minutes after procedure assessed by the 10-cm visual analog scale.; Result(s): Lidocaine spray was the most effective medication for reducing pain during OEB (P-score = 0.83) and immediately after OEB (P-score = 0.96). On the other hand, naproxen sodium was the most effective medication for reducing pain during outpatient hysteroscopy with EA (P-score = 1.00), followed by misoprostol plus lidocaine (P-score = 0.87).; Conclusion(s): Lidocaine spray, either alone or with topical application of lidocaine, is the most effective medication for reducing the pain during and after the OEB. Naproxen sodium is the most effective analgesic option during outpatient hysteroscopy with EA. (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Abboud, M., et al. (2020). "The Health Effects of Vitamin D and Probiotic Co-Supplementation: A Systematic Review of Randomized Controlled Trials." Nutrients 13(1).
	Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6-12 weeks, and included 50-105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and Lactobacillus , Bifidobacterium , and Streptococcus . Comparators were placebo, vitamin D, lower vitamin D dose, and probiotics and lower vitamin D dose. The co-supplementation yielded greater health benefits than its comparators did in all studies except in one assessing IBS. Beneficial effects included decreased disease severity, improved mental health, metabolic parameters, mainly insulin sensitivity, dyslipidemia, inflammation, and antioxidative capacity, and lower use of healthcare. Co-supplementation of vitamin D and probiotics generated greater health benefits than its comparators did. More studies in other diseases and various populations are needed to confirm these findings and to elucidate the optimal form, composition, and frequency of this co-supplementation.

Abby, D., et al. (2021). "What are the emotional impacts of conservative management for women experiencing early miscarriage – a systematic review."
	
Abdalla Mohammed, A., et al. (2021). "The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence." Therapeutic Advances in Endocrinology and Metabolism 12: 2042018821989238.
	Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Metabolic consequences associated with PCOS include, but are not limited to, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). This narrative review aims to provide a comprehensive overview of the potential therapeutic roles of the incretin-based therapies in the management of PCOS.; Methods: We performed a systematic search of databases including PubMed, MEDLINE and EMBASE up to 1 October 2020. We developed a search string of medical subject headings (MeSH) including the terms PCOS, incretin mimetics, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 receptor antagonists (GLP-1 RAs), liraglutide, exenatide, semaglutide, dipeptidyl peptidase-4 (DPP-4) inhibitors, combined with IR, testosterone and sex hormone-binding globulin (SHBG).; Results: We identified 854 relevant articles and, after the initial screening, eight interventional animal studies, one observational animal study, 14 interventional human studies, two case-control studies and one systematic review were included. These studies showed the potential significant roles of GLP-1 RAs and DPP-4 inhibitors in the management of PCOS, with significant improvements in the metabolic parameters, including substantial weight reduction and improved insulin sensitivity. These agents also improved the hormonal parameters through decreased free androgen and increased SHBG. Moreover, they improved menstrual regularity, increased fertility with enhanced ovulation and pregnancy in obese women with PCOS.; Conclusion: GLP-1 RAs and DPP-4 inhibitors have a promising therapeutic role in PCOS; however, larger clinical trials are needed to establish the role of incretin-based therapies in the management of PCOS.; Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest. (© The Author(s), 2021.)

Abdallah, K. S., et al. (2021). "Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial." Reproductive Biomedicine Online 43(4): 663-669.
	RESEARCH QUESTION: Does intrauterine administration of HCG before embryo transfer improve live birth rate during IVF cycles? DESIGN: A parallel, randomized controlled trial conducted between July 2018 and February 2020. Infertile women (n = 181) scheduled for fresh or vitrified-warmed embryo transfer after IVF carried out for any indication were randomized in a 1:1 ratio to receive either HCG (500 IU in 0.1 ml of tissue culture media) or culture media (0.1 ml of tissue culture media) via intrauterine injection 4 min before embryo transfer. In both groups, an intrauterine insemination catheter was used for administering the medication. Primary outcome was live birth, with ongoing pregnancy and clinical pregnancy as secondary outcomes. Analysis was based on intention-to-treat principle. RESULTS: Baseline and cycle characteristics were comparable between the two groups. In the control group, one woman with a confirmed clinical pregnancy was lost to follow-up. Live birth rates were 24% (22/90) in the HCG group versus 19% (17/90) in the control group (RR 1.29, 95% CI 0.74 to 2.27). Clinical pregnancy and ongoing pregnancy rates were 34% versus 26% (RR 1.31, 95% CI 0.84 to 2.04) and 24% versus 19% (RR 1.29, 95% CI 0.74 to 2.27) in the HCG and the control groups, respectively. CONCLUSION: Intrauterine injection of HCG before embryo transfer did not improve live birth rates in women undergoing IVF. As the study was designed to detect a 20% difference between groups, a smaller, clinically important difference could not be ruled out. Treatment outcomes were lower than expected in the control group.

Abdelaziz, A., et al. (2021). "Transvaginal radiofrequency energy for the treatment of urinary stress incontinence: A comparison of monopolar and bipolar technologies in both pre- and post-menopausal patients." Neurourology and Urodynamics 40(7): 1804-1810.
	Aim: A study to compare the effect of two different radio frequency energy models (mono polar and bipolar) for the treatment of urinary stress incontinence.; Methods: Retrospective chart review, which was conducted at 2 sites, 69 patients received treatment with a bipolar radiofrequency device. Out of those 69 patients, 13 patients received bipolar in conjugation with CO 2 laser treatment, while 32 patients received monopolar frequency. The study protocol normally consists of three sessions of treatment. Each session was four weeks apart with a whole 6-month duration follow-up. Results were evaluated by urogenital distress inventory (UDI)-6 questionnaire before and after treatment.; Results: The bipolar group improved UDI-6 scores across time more so than did the monopolar group with some evidence suggesting that the bipolar radiofrequency treatment was more effective compared to the monopolar radiofrequency. Three months after treatment, the bipolar group UDI-6 values were lower than those of the monopolar group. Six months after treatment, the UDI-6 scores increased in both groups, suggesting decrease efficacy with time however, the bipolar group's UDI-6 scores were consistently lower than the monopolar group's scores.; Conclusion: This study shows benefit of both monopolar and bipolar radiofrequency device in patients with stress urinary incontinence and mixed UI, with bipolar RF more efficacious than monopolar RF. More randomized prospective studies are needed to confirm these findings. (© 2021 Wiley Periodicals LLC.)

Abdel-Fattah, M., et al. (2022). "Single-incision mini-slings for stress urinary incontinence in women." New England Journal of Medicine 386(13): 1230-1243.
	BACKGROUND Until recently, synthetic midurethral slings (made of mesh or tape) were the standard surgical treatment worldwide for female stress urinary incontinence, if conservative management failed. Data comparing the effectiveness and safety of newer single-incision mini-slings with those of standard midurethral slings are limited. METHODS We performed a pragmatic, noninferiority, randomized trial comparing mini-slings with midurethral slings among women at 21 U.K. hospitals during 36 months of follow-up. The primary outcome was patient-reported success (defined as a response of very much or much improved on the Patient Global Impression of Improvement questionnaire) at 15 months after randomization (approximately 1 year after surgery). The noninferiority margin was 10 percentage points. RESULTS A total of 298 women were assigned to receive mini-slings and 298 were assigned to receive midurethral slings. At 15 months, success was reported by 212 of 268 patients (79.1%) in the mini-sling group and by 189 of 250 patients (75.6%) in the midurethral-sling group (adjusted risk difference, 4.6 percentage points; 95% confidence interval [CI], -2.7 to 11.8; P<0.001 for noninferiority). At the 36-month follow-up, success was reported by 177 of 246 patients (72.0%) and by 157 of 235 patients (66.8%) in the respective groups (adjusted risk difference, 5.7 percentage points; 95% CI, -1.3 to 12.8). At 36 months, the percentage of patients with groin or thigh pain was 14.1% with mini-slings and 14.9% with midurethral slings. Over the 36-month follow-up period, the percentage of patients with tape or mesh exposure was 3.3% with mini-slings and 1.9% with midurethral slings, and the percentage who underwent further surgery for stress urinary incontinence was 2.5% and 1.1%, respectively. Outcomes with respect to quality of life and sexual function were similar in the two groups, with the exception of dyspareunia; among 290 women responding to a validated questionnaire, dyspareunia was reported by 11.7% in the mini-sling group and 4.8% in the midurethral-sling group. CONCLUSIONS Single-incision mini-slings were noninferior to standard midurethral slings with respect to patient-reported success at 15 months, and the percentage of patients reporting success remained similar in the two groups at the 36-month follow-up.Copyright © 2022 Massachusetts Medical Society.

Abdel-Fattah, M. S., et al. (2023). "Single-incision mini-slings versus standard mid-urethral slings in the surgical management of female stress urinary incontinence: An updated systematic review and meta-analysis." European Urology 83(Supplement 1): S1250.
	Introduction & Objectives: Stress urinary incontinence is a prevalent, burdensome condition commonly treated surgically using synthetic standard mid-urethral slings (SMUS). An updated systematic review and meta-analysis of RCTs comparing Single Incision Mini-Slings (SIMS) versus Standard Mid-Urethral Slings (SMUS) in the surgical management of female stress urinary incontinence (SUI). To evaluate the efficacy, safety and cost-effectiveness of SIMS compared to SMUS (retro-pubic and transobturator tension-free vaginal tapes) in the Surgical Management of Female SUI. Material(s) and Method(s): Literature search was performed for all RCTs and quasi RCTs comparing SIMS to either TO-TVT or RP-TVT. The literature search had no language restrictions and was conducted on 18th January 2021 and planning to be updated on February 2023 to include our SIMS trial results which was published in NEJM March 2022. The primary outcomes were patient-reported and objective cure rates and were segregated into: short (12-18 months), mid (19-59 months), and longer-term (>= 60 months) follow-up. Secondary outcomes included: quality of life and sexual function, pain scores, operative data, perioperative complications, and cumulative adverse event rates. The GRADE methodology was used to subjectively assess quality of included studies and certainty of outcomes. Data were analysed using Review Manager 5.4.1. Meta-analyses of TVTSecurTM vs. SMUS are presented separately having been withdrawn from clinical practice. Result(s): Meta-analysis demonstrated no significant difference between SIMS (excluding TVT-Secur) and SMUS for mid-term patient-reported success (risk ratio [RR]: 0.98; 95% confidence interval [CI], 0.95-1.02) and objective cure rate (RR: 0.97; 95% CI, 0.93-1.01). Long-term data were lacking. SIMS demonstrated higher reoperation rates (RR: 1.92; 95% CI, 1.18-3.12), but no significant difference for de-novo dyspareunia (RR: 1.26; 95% CI, 0.57-2.82), or mesh exposure (RR: 0.98; 95% CI, 0.44-2.20), compared to SMUS. Favourable surgical data and reduced postoperative pain was observed but remains questionable. Conclusion(s): Excluding TVT-Secur, SIMS there was no evidence of significant difference in patient-reported and objective cure between currently used SIMS and SMUS at mid-term follow-up. Results should be interpreted with caution due to the heterogeneity of the trials included.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Abdelhafez, M. A., et al. (2023). "Psychiatric illness and pregnancy: A literature review." Heliyon 9(11): e20958.
	BACKGROUND: Women of reproductive age frequently suffer from psychiatric disorders. The risk of developing anxiety, bipolar, and depressive disorders is especially significant during the perinatal period. OBJECTIVES: This article aims to identify and discuss the different psychiatric conditions that might affect pregnant women and update the mother's carers about the recent and updated bidirectional relationship between psychiatric disease and adverse pregnancy outcomes, As well as the most updates in diagnostic and management strategies. METHODS: A thorough analysis of the literature was conducted using database searches in EMBASE, Science Direct, Google Scholar, Scopus, and PubMed to obtain the objectives and aim of the study. RESULTS: The presence of maternal mental illness during pregnancy has been linked to preterm delivery, newborn hypoglycemia, poor neurodevelopmental outcomes, and disturbed attachment. Placental anomalies, small-for-gestational-age foetuses, foetal discomfort, and stillbirth are among more undesirable perinatal outcomes. CONCLUSIONS: Pregnancy-related psychiatric disorders are frequent. The outcomes for pregnant women, infants, and women's health are all improved by proper diagnosis and treatment of psychiatric problems.

Abdelsalam, W. A., et al. (2021). "Predictive Factors of Para-Aortic Lymph Nodes Metastasis and Survival Advantages of Para-Aortic Lymphadenectomy in Early Stage Cervical Cancer." Journal of Gynecologic Surgery 37(3): 205‐213.
	Background: Performing dissection of para‐aortic lymph nodes (LNs) during radical hysterectomy is still optional and must be individualized. The clinical benefits of performing lymphadenectomy are not only for detection of occult metastases but it could positively affect the survival of patients. Aim of the Study: To assess the predictive clinical and pathologic parameters of occurrence of para‐aortic LNs metastasis in early stage cervical cancer patients (stages I and II) in addition to evaluate of the effect of the extent of lymphadenectomy on patients' survival. Patients and Methods: We included 60 patients with cancer cervix stages I‐II, we randomly divided them into the following: first group was managed by radical hysterectomy, dissection of both pelvic and para‐aortic LNs and second group underwent radical hysterectomy with dissection of only pelvic LNs. Results: We found that presence of deep stromal and uterine body invasion, ovarian spread, presence of pelvic LN metastasis, and presence of gross enlargement of para‐aortic LN were related to positive para‐aortic LNs (p < 0.001). Patients with para‐aortic LNs metastases have unfavorable disease‐free survival (DFS) and unfavorable overall survival (OS) rates (p < 0.001). DFS and OS rates were more favorable in patients who underwent para‐aortic lymphadenectomy than the other group who underwent only pelvic lymphadenectomy. Conclusions: Predictive factors for para‐aortic LNs metastases in patients with early stage cervical cancer are presence of lympovascular invasion and pelvic LNs spread. Additionally performing para‐aortic lymphadenectomy has survival benefits mainly in high‐risk patients with higher stage and widespread pelvic LNs metastases. Clinical Registration Number, NCT03361730. (J GYNECOL SURG 37:205)

Abdi, F., et al. (2021). "Impact of phytoestrogens on treatment of urogenital menopause symptoms: A systematic review of randomized clinical trials." European Journal of Obstetrics, Gynecology, and Reproductive Biology 261: 222-235.
	Objective: Menopause symptoms affect the various dimensions of women's lives and they can lead to reduction of their quality of life. Phytoestrogens can be used as an approach to diminish these symptoms. The aim of this systematic review was to investigate the effect of phytoestrogens on the treatment of urogenital menopause symptoms.; Study Design: PubMed, EMBASE, Web of Science, Cochrane library,Scopus and ProQuest were systematically searched from 2000-2020. All randomized clinical trials were included. The quality of the selected papers was evaluated by the CONSORT checklist.; Results: 33 eligible high-quality papers were reviewed. Various forms of phytoestrogens such as Pueraria Mirifica, fennel, Hop plant(Humuluslupulus L.), Glycine Max (L.) Merr, soy, red clover, black cohosh, ginsing, cimicifugaracemosa, genistein, diadzein, glycitein and isoflavone in the form of oral capsules and pill, food supplement, enriched powder, vaginal gel, cream and suppository could improve menopausal urogenital symptoms. The recovery rate in vaginal use of these phytoestrogens was greater than other consumptions.; Conclusions: After using a variety of phytoestrogens in different forms indicators of urogenital atrophy and urinary disorders improved and women's sexual function improved after treatment. The use of phytoestrogens as a safe, low-risk compared to hormone therapy and almost accessible method for women can relieve urogenital symptoms and promote the sexual satisfaction and quality of life.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abdnezhad, R. and M. Simbar (2020). "A review of the effective herbal medicines on hot flashes in menopausal women." Iranian Journal of Obstetrics, Gynecology and Infertility 23(8): 107-119.
	Introduction: Vasomotor symptoms occur in approximately 75% of menopausal women. Hot flash is the main reason of women's referring to receive menopausal care. Estrogen therapy is the most effective way to treat symptoms; given the known risks of hormone therapy, many women are interested to use herbal medicines for treatment of menopausal symptoms including hot flushes. Therefore, this study was performed with aim to evaluate the clinical trials conducted to evaluate the effectiveness of herbal medicines for treatment of hot flashes. Method(s): In this review study, to find the related articles, the databases of SID, Pubmed, Scopus and Web of Science were searched using the keywords of Menopause, Herbal medicine, medicine and Hot flash from 2002-2019. The articles which were performed as clinical trial were selected. Result(s): 31 randomized clinical trials were identified. These studies had investigated Vitagnus (2), soybean (4), Black cohosh (3), Ginkgo biloba (2), sage (4), Valerian (2), Flaxseed (2), red clover (5), Hypericum perforatum (1), evening primrose (2), fenugreek (1) and passion flower (1), and one study was also done as combination. It seems that phytoestrogens and lignans found in these plants can reduce the severity and duration of hot flashes with minimal side effects. Conclusion(s): Overall, the findings of this study showed that herbal medicine which belongs to phytoestrogens or lignans like as Vitagnus, licorice, soy, red clover, flax seeds, sage, passion flower, valerian, Hypericum and evening primrose can lead to improvement of hot flashes, but further studies in larger populations are needed.Copyright © 2020, Mashhad University of Medical Sciences. All rights reserved.

Abdolahian, S., et al. (2020). "Effect of lifestyle modifications on anthropometric, clinical, and biochemical parameters in adolescent girls with polycystic ovary syndrome: a systematic review and meta-analysis." BMC Endocrine Disorders 20(1): 71.
	Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. This study aimed to compare the effects of lifestyle interventions on anthropometric, clinical, and biochemical parameters in adolescent girls with PCOS.; Methods: PubMed, Scopus, and Web of Science was systematically searched to retrieve studies investigating the effects of lifestyle modifications in adolescent girls with PCOS, which were published up to December 2019. The primary outcome was Body Mass Index (BMI) and secondary outcomes were all manifestations of PCOS, including clinical, metabolic, and hormonal parameters. Random effect meta-analysis was applied for significant results. Publication bias was assessed using the Egger test.; Results: This study showed significant improvements in luteinizing hormone (LH) (Pooled SMD = - 0.1.23; 95% CI, - 2.44 to - 0.03), and Free Androgen Index (FAI) levels (Pooled SMD = - 0.78 95% CI, - 0.1.42 to - 0.13) in adolescent girls receiving lifestyle intervention compared to baseline. This study also revealed that diet modifications alone were associated with a significant decrease in Body Mass Index (BMI) (Pooled SMD = - 0.45; 95% CI, - 0.76 to - 0.13), and FG score (Pooled SMD = - 0.81; 95% CI, - 1.33 to - 0.28). Exercise interventions were associated with significant changes in the menstrual cycles (Pooled SMD = 1.16; 95% CI, 0.72 to 1.61), Ferriman-Gallwey (FG) score (Pooled SMD = - 0.57; 95% CI, - 0.99 to - 0.15), LH (Pooled SMD = - 056; 95% CI, - 0.98 to - 0.14), Anti-Müllerian Hormone (AMH) (Pooled SMD = - 0.81; 95% CI, - 0.1.24 to - 0.38), and Triglyceride (TG) levels (Pooled SMD = - 0.32; 95% CI, - 0.62 to - 0.02).; Conclusion: This meta-analysis concluded lifestyle interventions, such as diet and exercise, can improve some clinical, metabolic, and hormonal parameters in adolescent girls with PCOS.

Abdulkhalikova, D., et al. (2022). "Reproductive Outcome After GnRH Agonist Triggering With Co-Administration of 1500 IU hCG on the Day of Oocyte Retrieval in High Responders: A Long-Term Retrospective Cohort Study." Frontiers in Endocrinology 13: 826411.
	While triggering oocyte maturation with GnRH agonist (GnRHa) seems to be safe and effective in terms of the risk of developing OHSS and the number of metaphase II oocytes, it nevertheless results in luteal phase deficiency. To date, strategies have been developed in order to rescue defective luteal phase of GnRHa triggered cycles. Our study aimed to assess the reproductive outcome of GnRHa triggered cycles combined with modified luteal support (1500 IU hCG at the day of oocyte retrieval) in women with high ovarian response and to compare the outcome with hCG triggered cycles in GnRH antagonist IVF-ICSI procedures. A retrospective cohort database review of the results of GnRH antagonist IVF-ICSI cycles was conducted at a tertiary-care IVF center in Ljubljana, Slovenia. A total of 6126 cycles, performed from January 1, 2014, to December 31, 2020, were included in the final analysis. Final oocyte maturation was performed with either 5000, 6500, or 10,000 IU hCG (women with normal ovarian response) or 0.6 mg GnRHa (buserelin), supplemented with 1500 IU hCG on the day of oocyte retrieval (in women with high ovarian response). In cases of excessive ovarian response and/or high risk of OHSS luteal support was not introduced and all good quality blastocysts were frozen. According to significant differences in patients' age and the number of oocytes in the two groups, matching by age and number of oocytes was performed. No significant differences were observed regarding pregnancy rate per embryo transfer, rate of early pregnancy loss, and livebirth rate per pregnancy between the GnRHa and hCG trigger groups, respectively. A significant difference in the number of developed embryos and blastocysts, as well as the number of frozen blastocysts, was seen in favor of the GnRHa trigger. However, the birth weight in the GnRHa trigger group was significantly lower.; Conclusion: The results of our study support the use of GnRHa for final oocyte maturation in GnRH antagonist IVF cycles in women with high ovarian response. Luteal phase rescue was performed by co-administration of 1500 IU hCG on the day of oocyte retrieval and estradiol and progesterone supplementation. In our experience, such an approach results in a comparable reproductive outcome with hCG trigger group.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Abdulkhalikova, Bokal, Stimpfel, Ciglar and Korosec.)

Abdul-Latif, M., et al. (2023). "Functional Magnetic Resonance Imaging in Cervical Cancer Diagnosis and Treatment." Clinical Oncology 35(9): 598-610.
	Cervical Cancer is the fourth most common cancer in women worldwide. Treatment with chemoradiotherapy followed by brachytherapy achieves high local control, but recurrence with metastatic disease impacts survival. This highlights the need for predictive and prognostic biomarkers identifying populations at risk of poorer treatment response and survival. Magnetic resonance imaging (MRI) is routinely used in cervical cancer and is a potential source for biomarkers. Functional MRI (fMRI) can characterise tumour beyond anatomical MRI, which is limited to the assessment of morphology. This review summarises fMRI techniques used in cervical cancer and examines the role of fMRI parameters as predictive or prognostic biomarkers. Different techniques characterise different tumour factors, which helps to explain the variation in patient outcomes. These can impact simultaneously on outcomes, making biomarker identification challenging. Most studies are small, focussing on single MRI techniques, which raises the need to investigate combined fMRI approaches for a more holistic characterisation of tumour.Copyright © 2023

Abe, M., et al. (2022). "Is a freeze-all strategy necessary for all embryo transfers : Fresh embryo transfer without progesterone elevation results in an equivalent pregnancy rate to cryopreserved embryo transfer." The journal of medical investigation : JMI 69(3.4): 224-229.
	Objectives : It has been suggested that the clinical outcomes of frozen-thawed embryo transfer (ET) are superior to those of fresh embryo transfer. We examined whether a freeze-all strategy is necessary for all embryo transfers, and, if not, to evaluate the conditions in which the pregnancy rates of fresh embryo transfer and frozen-thawed ET did not differ. Methods : Patients who underwent blastocyst transfer at Tokushima University Hospital between 2008 and 2019 were enrolled. The clinical outcomes and clinical characteristics of 1,022 patients that underwent fresh embryo transfer and 1,728 patients that underwent frozen-thawed ET were examined retrospectively. We considered the factors that influenced the pregnancy outcomes of fresh embryo transfer. Results : The frozen-thawed ET group exhibited significantly higher pregnancy, live-birth, and miscarriage rates than the fresh embryo transfer group. In the fresh embryo transfer group, a high progesterone level on the day of the human chorionic gonadotropin (hCG) trigger and lower grade embryos were risk factors for a low pregnancy rate. However, in the cases in which the progesterone level was < 1.0 ng / mL the pregnancy rate was equal to that of frozen-thawed ET. Conclusions : A freeze-all strategy is not necessary for embryo transfers, but should be employed in cases involving pre-ovulatory progesterone elevation. J. Med. Invest. 69 : 224-229, August, 2022.

Abe, S. K. and M. Inoue (2021). "Green tea and cancer and cardiometabolic diseases: a review of the current epidemiological evidence." European Journal of Clinical Nutrition 75(6): 865-876.
	Green tea is commonly consumed in China, Japan, and Korea and certain parts of North Africa and is gaining popularity in other parts of the world. The aim of this review was to objectively evaluate the existing evidence related to green tea consumption and various health outcomes, especially cancer, cardiovascular disease and diabetes. This review captured evidence from meta-analyses as well as expert reports and recent individual studies. For certain individual cancer sites: endometrial, lung, oral and ovarian cancer, and non-Hodgkins lymphoma the majority of meta-analyses observed an inverse association with green tea. Mixed findings were observed for breast, esophageal, gastric, liver and a mostly null association for colorectal, pancreatic, and prostate cancer. No studies reported adverse effects from green tea related to cancer although consuming hot tea has been found to possibly increase the risk of esophageal cancer and concerns of hepatotoxity were raised as a result of high doses of green tea. The literature overall supports an inverse association between green tea and cardiovascular disease-related health outcomes. The evidence for diabetes-related health outcomes is less convincing, while the included meta-analyses generally suggested an inverse association between green tea and BMI-related and blood pressure outcomes. Fewer studies investigated the association between green tea and other health outcomes such as cognitive outcomes, dental health, injuries and respiratory disease. This review concludes that green tea consumption overall may be considered beneficial for human health.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Abenhaim, H. A., et al. (2022). "Progesterone for Prevention of Miscarriage & Preterm Birth in Women with First Trimester Bleeding: pREEMPT-Trial." American Journal of Obstetrics and Gynecology 226(1): S18.
	Objective: First trimester bleeding is associated with miscarriage and preterm birth for which progesterone has been suggested to improve outcomes. The objective of our study was to evaluate the effect of progesterone treatment throughout pregnancy on preventing miscarriage and preterm birth in pregnancies with first trimester bleeding. Study Design: Multicenter double‐blind placebo controlled randomized trial comparing vaginally administered Micronized Progesterone 200mg nightly from presentation until 34weeks of pregnancy with an identically appearing placebo. Subjects with vaginal bleeding and a live intrauterine pregnancy under 14weeks were offered study participation. Multifetal gestations, cervical insufficiency, recurrent pregnancy loss, or bleeding unrelated to placentation were excluded. Primary outcome was the occurrence of a live term pregnancy. Secondary outcomes included adverse maternal and newborn events and time to miscarriage / birth. Chi square analyses were used to compare proportions and Mann‐Whitney tests were used to compare time‐to‐event outcomes Results: 549 subjects were recruited and randomized of which 16 withdrew or were lost to follow‐up leaving 264 subjects in the progesterone group and 269 subjects in the placebo group. Baseline characteristics were comparable in both groups. As compared to subjects in the placebo group, the number of subjects having a live term birth among those in the progesterone group was 197 (74.6%) vs 190 (70.6%), p=0.30, respectively. As compared to subjects in the placebo group, those in the progesterone group had comparable risks of abortion under 20 weeks, 38 (14.4%) vs 43 (16.0%), p=0.94, preterm birth, 27 (10.2%) vs 33 (12.3%), p=0.46, and stillbirth 2 (0.9%) vs 3 (1.3%), p=0.65, respectively. There were no differences in adverse maternal or newborn outcomes, or in time‐to‐event for miscarriage or birth between the two groups. Conclusion: Progesterone prescribed throughout pregnancy is not effective in preventing miscarriage or prematurity in subjects presenting with first trimester vaginal bleeding in context of a live intrauterine pregnancy. [Formula presented]

Abitbol, J., et al. (2023). "Impact of robotic surgery on patient flow and resource use intensity in ovarian cancer." Journal of Robotic Surgery 17(2): 537-547.
	There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3 months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings.Copyright © 2022, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.

Ablon, G. and S. Kogan (2021). "A Randomized, Double-Blind, Placebo-Controlled Study of a Nutraceutical Supplement for Promoting Hair Growth in Perimenopausal, Menopausal, and Postmenopausal Women With Thinning Hair." Journal of drugs in dermatology 20(1): 55‐61.
	Hair loss is a complex and multi‐factorial problem that is associated with significant psychological morbidity in women. Menopausal women represent a significant percentage of those affected, since the menopausal hormonal transition can be a contributing factor. A novel nutraceutical supplement has been specifically formulated with phytoactives to improve hair growth and quality in menopausal women (Nutrafol® Women’s Balance Capsules). The objective of this 6‐month, randomized, double‐blind, placebo‐controlled study was to assess the safety and efficacy of this oral supplement to promote hair growth in perimenopausal, menopausal, and postmenopausal women with self‐perceived thinning. Subjects were randomized to the study supplement (n=40) or placebo (n=30). The primary endpoint was a statistically significant increase in the number of terminal and vellus hairs based on phototrichogram analysis. Daily intake of the nutraceutical supplement resulted in progressive and significant increase in terminal and total hair counts on days 90 (P<0.01) and 180 (P<0.01) compared to placebo. The vellus hair counts significantly increased for the active treatment group (P<0.05) by day 180 while significantly decreasing for the placebo group subjects. Hair shedding progressively and significantly decreased for the active group compared to placebo, culminating in a reduction of 32.41% by day 180 (P<0.01). The study supplement was well‐tolerated. ClinicalTrials.gov Identifier: NCT04048031 J Drugs Dermatol. 2021;20(1):55‐61. doi:10.36849/JDD.5701 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Ablon, G., et al. (2022). "A Long-Term Study of the Safety and Efficacy of a Nutraceutical Supplement for Promoting Hair Growth in Perimenopausal, Menopausal, and Postmenopausal Women." Journal of drugs in dermatology : JDD 21(7): 783.
	The prevalence of female hair loss and hair thinning increases with advancing age and is most common among post-menopausal women. Recent statistics show that by age 60, an estimated 80% of women experience hair loss. A previous publication detailing the results of the 6-month randomized, double-blind, placebo-controlled phase of this study demonstrated the ability of a nutraceutical supplement to significantly improve hair growth and shedding compared to placebo. Here, we present results from a subsequent 6-month, open-label extension phase assessing the continued safety and efficacy of this nutraceutical for promoting and improving hair growth and evaluate potential long-term benefits on quality of life and menopausal symptoms. After a total of 12 months with the active nutraceutical, subjects had progressive improvements in hair growth, quality, and shedding. Quality of life measures and menopausal symptoms also improved over the duration of the study. When transitioned to daily intake of the supplement, subjects previously treated with placebo achieved significant increases in all hair counts, a significant decrease in shedding, and significant improvement in blinded investigator global hair growth and quality assessments. The results of this long-term study demonstrate that continued use of a novel nutraceutical provides significant incremental improvement over the beneficial effects achieved during the initial 6-month randomized, placebo-controlled phase. Continued use may provide ongoing improvements in hair growth and exert a positive effect on secondary symptoms of menopause, and quality of life in perimenopausal, menopausal, and postmenopausal women with selfperceived thinning hair (ClinicalTrials.gov Identifier: NCT04048031). J Drugs Dermatol. 2022;21(7):776-783. doi:10.36849/JDD.6912.

Aboshama Rehab, A., et al. (2022). "The effect of hyoscine-N-butylbromide on pain perception during and after hysterosalpingography in infertile women: a systematic review and meta-analysis of randomised controlled trials." Human fertility (Cambridge, England) 25(3): 422-429.
	This paper reports a systematic review and meta-analysis of the effectiveness of hyoscine-N-butylbromide (HBB) administration in hysterosalpingography (HSG). Four electronic databases were searched for randomised controlled trials (RCTs) that compared HBB versus placebo or no intervention in infertile women undergoing HSG. Pain during and after HSG and different adverse events including nausea, vomiting, and dizziness were evaluated. Three RCTs with 335 patients were included. The analysis showed HBB was significantly effective in reducing pain during and after HSG (MD = -0.76 mm, 95% CI [-1.35, -0.17], p = 0.01) and (MD = -0.81 mm, 95% CI [-1.07, -0.56], p < 0.001), respectively. There were no significant differences in adverse events between HBB and control groups. The methodological evidence quality was high as evaluated by GRADEpro. In conclusion, this review provides good evidence that prior administration of HBB is effective in reducing induced pain during and after HSG with tolerable side effects.

Aboualsoltani, F., et al. (2020). "Therapeutic effects of citrus aurantium components on psychological states: A systematic review." Crescent Journal of Medical and Biological Sciences 7(4): 443-450.
	Objectives: Citrus aurantium L., frequently known as the sour or bitter orange, is native to Asia and, nowadays, is widely cultivated in different regions such as the Mediterranean. Different parts of C. aurantium are consumed as an alternative medicine in some areas to treat some diseases, and various recent studies have proven the potential of this medicinal plant. This review examined the therapeutic effects of C. aurantium components. Method(s): Tactful and progressive search strategies were developed to determine the studies. To this end, a large number of databases were evaluated, including Cochrane Library, PubMed/MEDLINE, Scopus, and Google Scholar (2010 to April 2019). Finally, 12 clinical trial studies were selected for evaluation and analysis, and the JADAD scale was used to evaluate the quality of the papers. Result(s): Of 546 papers found in the preliminary search, 12 clinical trials (1132 participants), which were written in English, were selected for structured reviews. The researches consisted of those which evaluated the therapeutic role of the plants in anxiety, depression, sleep quality, premenstrual syndrome, and menopausal symptoms. Conclusion(s): The review of clinical trials brings some evidence that different components of C. aurantium, especially its flower have therapeutic effects on particularly psychological states like anxiety, depression, and insomnia and aromatherapy by the essential oil is considered as the most used method of prescription. Therefore, C. aurantium can confidently be used in various disorders which have these psychological aspects among their symptoms.Copyright © 2020 The Author(s)

Abraham, F., et al. (2022). "Safely and practice of Foley Catheter for second trimester surgical abortion: a protocol for a systematic review."
	
Abrao, M. S., et al. (2021). "Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients." BMC Women's Health 21(1): 246.
	Background: Elagolix is an oral, gonadotropin‐releasing hormone (GnRH) receptor antagonist, that significantly reduces dysmenorrhea and non‐menstrual pelvic pain (NMPP) in women with moderate to severe endometriosis‐associated pain. Methods: Data were pooled from two 6‐month, placebo‐controlled, phase 3 studies (Elaris Endometriosis [EM]‐I and II) in which 2 doses of elagolix were evaluated (150 mg once daily and 200 mg twice daily). Pooled data from > 1600 women, aged 18–49, were used to evaluate the efficacy of elagolix and health‐related quality of life (HRQoL) in prespecified subgroups of women with various baseline characteristics. Results: Of the 1686 women treated, 1285 (76.2%) completed the studies. The percentages of women with clinically meaningful reductions in dysmenorrhea and NMPP were generally consistent by subgroup. Significant treatment by subgroup interaction was demonstrated for dysmenorrhea response in baseline analgesic use (p < 0.01) and previous history of pregnancy (p < 0.05) subgroups, and for NMPP response in the baseline NMPP score (p < 0.05) and history of pregnancy (p < 0.05) subgroups. Patient‐reported reduction in pain at month 3 was significant across all subgroups taking elagolix 200 mg BID, and significant across most subgroups with elagolix 150 mg QD. Women across subgroups experienced improvement within each domain of the Endometriosis Health Profile‐30 (EHP‐30), although significant treatment by subgroup interactions were observed in several categories. Conclusions: Elagolix was effective in reducing dysmenorrhea and NMPP, and improving HRQoL, compared with placebo across numerous subgroups of women with various baseline characteristics, covering a broad segment of the endometriosis disease and patient types. Clinical trial registration: ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01620528; https://www.clinicaltrials.gov/ct2/show/NCT01931670.

Abshirini, M., et al. (2021). "Effect of Greenshell TM mussel on osteoarthritis biomarkers and inflammation in healthy postmenopausal women: a study protocol for a randomized double-blind placebo-controlled trial." Trials 22(1): 498.
	Background: New Zealand Greenshell™ mussels (GSM; Perna canaliculus) have recently been shown to decrease cartilage degradation in a rat model of induced metabolic osteoarthritis (MetOA). However, this effect has not been investigated in human subjects. This study aims to determine the effect of GSM powder on biomarkers of cartilage metabolism, bone resorption, and inflammation in New Zealand healthy overweight/obese postmenopausal women who are at early stage or at high risk of OA.; Method: Fifty overweight or obese (BMI 25-35 kg/m 2 ) postmenopausal women (aged 55-75 years) will be recruited by advertisement. Participants will be randomized based on a double-blind randomization schedule and stratified randomization based on BMI and age distribution. The participant will be assigned with a 1:1 allocation ratio to receive 3 g/d whole meat GSM powder or placebo (sunflower seed protein) for 12 weeks. Data on socio-demographics, physical activity, and dietary intake will be collected for each subject. Cartilage turnover biomarkers [(C-telopeptide of type II collagen (CTX-II), C-propeptide of type II procollagen (CPII), Cartilage oligomeric matrix protein (COMP)], and bone resorption marker (CTX-I) will be measured in blood and urine samples. Inflammatory status (hs-CRP and cytokine panel) will be assessed and iron status will be measured. Body composition including fat mass (FM), lean mass (LM), and fat percentage will be measured using dual-energy X-ray absorptiometry (DXA). Joint pain and knee function will be assessed using a 100-mm visual analog scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively.; Discussion: This trial will be the first to explore the effects of whole meat GSM powder on cartilage turnover, bone resorption, and inflammation biomarkers in overweight/obese postmenopausal women. The results from this trial will provide evidence on the efficacy of GSM in the prevention of OA.; Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000413921p . Registration on 27 March 2020. (© 2021. The Author(s).)

Abshirini, M., et al. (2023). "Effect of green-lipped mussel ( Perna canaliculus ) supplementation on faecal microbiota, body composition and iron status markers in overweight and obese postmenopausal women: a randomised, double-blind, placebo-controlled trial." Journal of nutritional science 12: e58.
	The present study aimed to determine the effect of whole meat GSM powder on gut microbiota abundance, body composition and iron status markers in healthy overweight or obese postmenopausal women. This was a 3-months trial involving forty-nine healthy postmenopausal women with body mass index (BMI) between 25 and 35 kg/m 2 who were randomly assigned to receive 3 g/d of either GSM powder ( n 25) or placebo ( n 24). The gut microbe abundance, serum iron status markers and body composition were measured at the baseline and the end of the study. The between-group comparison at the baseline showed a lower abundance of Bacteroides and Clostridium XIVa in the GSM group compared with the placebo ( P = 0⋅04). At the baseline, the body fat (BF)% and gynoid fat% were higher in the GSM group compared with the placebo ( P < 0⋅05). No significant changes were found in any of the outcome measures, except for ferritin levels that showed a significant reduction over time (time effect P = 0⋅01). Some trend was observed in bacteria including Bacteroides and Bifidobacterium which tended to increase in the GSM group while their abundance decreased or remained at their baseline level in the control group. Supplementation with GSM powder did not result in any significant changes in gut microbe abundance, body composition and iron markers compared with placebo. However, some commensal bacteria such as Bacteroides and Bifidobacteria tended to increase following supplementation with GSM powder. Overall, these findings can expand the knowledge surrounding the effects of whole GSM powder on these outcome measures in healthy postmenopausal women. (© The Author(s) 2023.)

Abu-Zaid, A., et al. (2022). "Ascorbic Acid for Prevention of Intraoperative Blood Loss and Related Complications During Myomectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Cureus 14(11): e31571.
	Leiomyomas are inherently well-vascularized neoplasms; thus, they are very vulnerable to bleeding-associated complications during myomectomy. Ascorbic acid has well-established functions in tissue healing and the prevention of bleeding tendencies. Several randomized controlled trials (RCTs) have explored the antihemorrhagic utility of ascorbic acid administration during myomectomy. This research aimed to systematically and meta-analytically summarize the clinical antihemorrhagic efficacy of ascorbic acid (i.e., the intervention arm) versus placebo/no treatment (i.e., the control arm) during myomectomy. We electronically searched six sources, i.e., PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. Our search was from inception until October 2022. We used the Cochrane Risk of Bias Scale (version 2) to assess the quality of the included studies. We summarized the effect sizes as the mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI) in a fixed-effects or random-effects model. Overall, three RCTs met the inclusion criteria, comprising a total of 193 patients: 99 patients were allocated to the ascorbic acid arm, whereas 94 patients were allocated to the control arm. The overall study quality was "low" and "some concerns" risk of bias in two and one RCT(s), respectively. There was no significant difference between the ascorbic acid and control arms regarding the mean intraoperative blood loss (n=2 RCTs, MD = -190.29 ml, 95% CI [-626.62, 246.05], p=0.39) and mean change in hemoglobin level (n=3 RCTs, MD = -0.26 mg/dl, 95% CI [-0.56, 0.04], p=0.09), respectively. Conversely, the ascorbic acid arm had statistically significant reductions in the mean operative time (n=3 RCTs, MD = -24.10 min, 95% CI [-30.67, -17.53], p<0.001) and the rate of blood transfusion (n=3 RCTs, RR=0.36, 95% CI [0.15, 0.87], p=0.02) compared with the control arm. No serious adverse events related to ascorbic acid were identified. In conclusion, ascorbic acid administration was associated with several beneficial effects, including reductions in mean operative time and rate of blood transfusion, but without affecting the mean intraoperative blood loss and mean change in hemoglobin level. In view of the limitations of the present meta-analysis, the use of ascorbic acid as an antihemorrhagic additive among patients undergoing myomectomy is not strongly recommended.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Abu-Zaid et al.)

Abu-Zaid, A., et al. (2023). "Effect of selenium supplementation on cardiometabolic risk factors in polycystic ovary syndrome (PCOS) patients: A systematic review and meta-analysis of randomized clinical trials." PharmaNutrition 26: 100358.
	Background: Polycystic ovary syndrome (PCOS) has been shown to be associated with cardiometabolic risk factors. Selenium (Se) is a naturally occurring mineral trace element that constitutes an essential component of selenoproteins and plays a vital role in antioxidant defense. This systematic review and meta-analysis aims to assess the effects of selenium supplementation on cardiometabolic risk factors in patients with PCOS. Method(s): MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched up to March 2023 for randomized clinical trials that evaluated the effect of oral selenium supplementation on patients with PCOS. We employed a random-effects model to generate pooled estimates and 95% confidence intervals (CI). Result(s): Seven trials published between 2015 and 2022 were included. All the included studies were double blind, placebo-controlled trials. Selenium supplementation resulted in a significant decrease in VLDL (SMD = -0.35, 95% CI: -0.65; -0.05), MDA (SMD = -0.89, 95% CI: -1.21; -0.57) and hs-CRP (SMD = -0.38, 95% CI: -0.73; -0.03), as well as a significant increase in QUICKI (SMD = 0.78, 95% CI: 0.47; 1.09). The current meta-analysis did not find any significant changes in FPG, insulin, HOMA-IR, TC, TG, HDL, LDL, TAC, GSH, NO, SHBG, total testosterone, or mFG score for PCOS patients following selenium supplementation compared to placebo. Conclusion(s): Selenium supplementation may serve as a good adjunct therapy in patients with PCOS to decrease lipid peroxidation and inflammatory status. Moreover, selenium may improve insulin sensitivity in these patients. However, the overall effects of selenium on all cardiometabolic risk factors in PCOS patients still need to be evaluated through large population and long duration RCTs.Copyright © 2023 Elsevier B.V.

Achen, G., et al. (2021). "[Epithelial ovarian cancers and minimally invasive cytoreductive surgery after neoadjuvant chemotherapy: A systematic review]." Gynecologie, obstetrique, fertilite & senologie 49(10): 736-743.
	Introduction: Advanced epithelial ovarian cancer (EOC) is associated with high mortality and often managed first with neoadjuvant chemotherapy (NACT) followed by debulking surgery. Laparoscopic surgery with or without robotic assistance (Minimally Invasive Surgery (MIS)) may represent a beneficial option for these patients. The objective of this literature review is to clarify the place of MIS in the management of advanced EOC for selected patients.; Method: Pubmed, Cochrane and Clinicaltrials.gov online databases were used for this review, to select English or French published articles.; Results: We selected 11 original articles published between 2015 and 2020, 6 of which compared MIS and laparotomy. Among these 11 studies, 8 were retrospective cohorts, 2 were phase II trials, and one was a case-control study. In total, there were 3721 patients, of which 854 (23%) were treated with MIS. The robotic assistance was used with 224 patients (26%) of those MIS patients. Looking specifically at MIS patients, the laparoconversion rate was 9.5%, the rate of complete resection (CC-0) was 83.4%. Finally, the MIS complication rate was 1% intraoperatively and 12% postoperatively. The rate of complete resection, postoperative complication, as well as overall survival (OS) were comparable between patients treated with MIS or laparotomy. One study found an improved disease-free survival (DFS) in MIS versus laparotomy (18 months versus 12 months; P=0.027).; Conclusion: MIS seems feasible, effective, and reliable in comparison to laparotomy for the completion of cytoreductive surgery after NACT without compromising oncological safety. Prospective randomized controlled trials are needed to confirm the role of MIS in advanced EOC. (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Acién, P., et al. (2021). "Long-term outcomes of transvaginal ultrasound-guided aspiration versus traditional conservative surgery as treatment for endometriomas: A retrospective study of cohorts." The Journal of Obstetrics and Gynaecology Research 47(4): 1462-1471.
	AIM: To evaluate if the long-term results (on fertility, need of hysterectomy and persistence of endometriosis) after a minimally invasive intervention (transvaginal ultrasound-guided puncture-aspiration [TUGPA]) for endometriomas are significantly different from performing the traditional conservative surgery (CS) by laparoscopy or laparotomy. METHODS: We performed a retrospective study of cohorts on patients undergoing surgery for ovarian endometriomas between January 1998 and April 2015. Cohort 1 consisted of 75 women whose first intervention for endometriomas had been TUGPA. For the cohort 2, we selected a randomized paired case in which the first operation for endometriomas had been CS by laparoscopic or laparotomy (another set of 75 patients). RESULTS: There were significantly more recurrences and the time to recurrence and repetition of operations were also significantly shorter in patients with TUGPA. However, there were no significant differences in overall pregnancy/delivery outcomes, in hysterectomy performances, or in endometriosis persistence at the last follow-up visit. There were no significant differences related to the symptoms or to analytical presurgical values but the application of multivariate analysis with binary logistic regression to each dependent variable adjusted for age, symptoms, and presurgical analyses showed a significant risk of recurrence and reoperation of TUGPA versus CS. CONCLUSIONS: Those patients with endometriomas who underwent TUGPA (with or without associated medications) had a significant increase in recurrence and the need for reoperation. However, in the long-term there were no significant differences in the results of pregnancy/childbirth, need for hysterectomy, or in the clinical or doubtful persistence of endometriosis.

Ackert Kathleen, E., et al. (2023). "Implementation of an enhanced recovery after surgery (ERAS) protocol for total abdominal hysterectomies in the division of gynecologic oncology: a network-wide quality improvement initiative." Journal of osteopathic medicine 123(10): 493-498.
	Context: Enhanced Recovery After Surgery (ERAS) protocols have been shown to decrease length of stay and postoperative opioid usage in colorectal and bariatric surgeries performed at large academic centers. Hysterectomies are the second most common surgical procedure among women in the United States. Hysterectomies performed in an open fashion, or total abdominal hysterectomies (TAHs), account for a large portion of procedures performed by gynecologic oncologists secondary to current oncology guidelines and surgical complexity. Implementation of an ERAS protocol for gynecologic oncology TAHs is one way in which patient outcomes may be improved.; Objectives: An ERAS protocol for gynecologic oncology surgeries performed in a community hospital was instituted with the goal to optimize patient outcomes preoperatively. The primary outcome of interest was to reduce patient opioid usage. Secondary outcomes included compliance with the ERAS protocol, length of stay, and cost. Thirdly, this study aimed to demonstrate the unique challenges of implementing a large-scale protocol across a community network.; Methods: An ERAS protocol was implemented in 2018, with multidisciplinary input from the Departments of Gynecologic Oncology, Anesthesia, Pharmacy, Nursing, Information Technology, and Quality Improvement to develop a comprehensive ERAS order set. This was implemented across a 12-site hospital system network that consisted of both urban and rural hospital settings. A retrospective review of patient charts was performed to assess measured outcomes. Parametric and nonparametric tests were utilized for statistical analysis with p<0.05 denoting statistical significance. If the p value was >0.05 and <0.09, this was considered a trend toward significant.; Results: A total of 124 patients underwent a TAH utilizing the ERAS protocol during 2018 and 2019. The control arm consisted of 59 patients who underwent a TAH prior to the ERAS protocol intervention, which was the standard of care in 2017. After 2 years of implementation of the ERAS protocol intervention, we found that 48 % of the ERAS patients had minimal opioid requirements after surgery (oral morphine equivalent [OME] range 0-40) with decreased postoperative opioid requirements in the ERAS group (p=0.03). Although not statistically significant, utilization of the ERAS protocol for gynecologic oncology TAHs trended toward shorter hospital length of stay from 5.18 to 4.17 days (p=0.07). The median total hospital costs per patient also showed a nonsignificant decrease in cost from $13,342.00 in the non-ERAS cohort and $13,703.00 in the ERAS cohort (p=0.8).; Conclusions: A large-scale quality improvement (QI) initiative is feasible utilizing a multidisciplinary team to implement an ERAS protocol for TAHs in the division of Gynecologic Oncology with promising results. This large-scale QI result was comparable to studies that conducted quality-improvement ERAS initiatives at single academic institutions and should be considered within community networks. (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Acs, M., et al. (2022). "Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer." Cancers 14(14).
	Background: The usage of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gynecological cancers is increasing. Methods: Prospectively collected data of 85 advanced primary ovarian/fallopian tube cancer and peritoneal carcinoma patients of a single center were investigated. Results: A total 48, 37, 62, and 25 patients were enrolled into the HIPEC with/without neoadjuvant chemotherapy (upfront vs. interval) and into the 60 min and 90 min long HIPEC groups, respectively. Better overall survival (OS) was observed in the 90 min HIPEC group (p = 0.0330), compared to the 60 min HIPEC group. Neither OS (p = 0. 2410), disease-specific (p = 0. 3670), nor recurrence-free survival (p = 0.8240) differed between upfront and interval HIPEC. Higher peritoneal carcinomatosis index (PCI) values were associated with worse disease-specific survival (p = 0.0724). Age (p = 0.0416), body mass index (p = 0.0044), PCI (p < 0.0001), the type (p = 0.0016) and duration (p = 0.0012) of HIPEC, and increased perioperative morbidity (p < 0.0041) had the greatest impact on OS. Conclusions: Increasing data support the value of HIPEC in the treatment of advanced ovarian cancer. Ongoing prospective studies will definitively clarify the role and timing of this additional therapeutic approach.

Actrn (2021). "The effect of a paracervical block prior to total laparoscopic hysterectomy on patient's quality of recovery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The intervention group will receive 20mL of bupivacaine 0.5% with 1:200,000 adrenaline infiltrated via paracervical block, after induction of general anaesthesia and prior to the initial surgical incision. The intervention is TGA approved. Five millilitres of the solution will be injected at the 3, 5, 7, and 9 o’clock positions of the cervicovaginal junction at a depth of 10mm as described in the 7th edition of Te Linde’s Operative Gynecology. The injection will be prepared at the hospital pharmacy. The Study Coordinator will deliver this to the surgeon in theatre. A copy of the randomisation sheet documenting the drug administered will be filed in the patients medical records. The surgeon, patient and anaesthetist will not be aware of which preparation is used. CONDITION: Anaesthesiology ‐ Pain management Post operative pain;Hysterectomy; ; Post operative pain ; Hysterectomy Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders Surgery ‐ Other surgery PRIMARY OUTCOME: Completion of Quality of recovery questionnaire (QoR‐15) to measure patient reported quality of recovery.[Measured 24‐36 hours post operatively] SECONDARY OUTCOME: Assessing Length of Hospitalisation by accessing patient medical records ; [At the time of hospital discharge ; ] Completion of Quality of recovery questionnaire (QoR‐15) to measure patient reported quality of recovery.[measured 7 days post surgery.] Composite opioid measured by accessing patient medical records[Measured up to 24 hours post surgery] Nausea and Vomiting[Assessed by requirement for anti‐emetics, which will be determined by accessing patient medical records. Antiemetic use will be documented for the first 24 hours post surgery.] Opioid use in Post Anesthesia Care Unit by accessing patient medical records. ; [Period whilst in Post Anesthesia Care Unit ; ] Pain score utilising visual analogue scale at rest [Measured at a single set timepoint between 24‐36 hours post surgery. ; ] Pain score utilising visual analogue scale at rest [Measured at day 7 post operatively] Pain score utilising visual analogue scale at time of mobilisation [Measured at a single timepoint between 24‐36 hours post surgery. ; ] Pain score utilising visual analogue scale at time of mobilisation [Measured at day 7 post operatively] Time in Post Anesthesia Care Unit by accessing patient medical records. ; [Timepoint: from surgery finish time to time returned to ward ; ] Time to mobilisation after surgery by accessing patient medical records. ; [Measured up to 36 hours post surgery ; ] INCLUSION CRITERIA: 1. Women undergoing a total laparoscopic hysterectomy (TLH) plus or mimus bilateral Salpingo‐oophorectomy (BSO) for any of the following conditions: a. Heavy menstrual bleeding/ abnormal uterine bleeding b. Stage 1 and 2 Endometriosis c. Adenomyosis d. Risk reduction surgery e.g. carriers of BRCA1/2 gene faults, Lynch Syndrome or women considered high risk due to family history e. Complex adnexal masses not suspicious for malignancy f. Early stage cervical cancer requiring simple hysterectomy 2. Patients aged 18 years of age and over 3. Fluent in English

Actrn (2021). "The effect of lignocaine on pain outcomes for women undergoing gynaecological surgery for chronic pelvic pain." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Double blind randomised controlled trial of the use of peri‐operative intravenous lignocaine compared to placebo matched control intravenous saline at the time of operative laparoscopy for chronic pelvic pain conditions. Description of drug intervention: Name ‐ Lignocaine, or Lidocaine (International Non‐proprietary Name) Dose, duration and mode of administration ‐ 1.5mg/kg intravenous bolus with induction of anaesthesia (max 200mg), followed by 2mg/kg/hour intravenous infusion during anaesthesia. Cease infusion prior to emergence from anaesthesia. CONDITION: Anaesthesiology ‐ Pain management Chronic pelvic pain; ; Chronic pelvic pain Renal and Urogenital ‐ Other renal and urogenital disorders Surgery ‐ Other surgery PRIMARY OUTCOME: Visual Analogue Scale (VAS) pain scores [Measured at 2, 4, 6 and 12‐24 hours postoperative] SECONDARY OUTCOME: Change in pain assessment on specifically designed questionnaire from preoperative to postoperative assessment at 3 months ‐ questionnaire designed specifically for this study ; [3 months postoperative] Change in Quality of life scores (12‐item short form survey [SF‐12], Fatigue survey score) from preoperative to postoperative assessment at 6 weeks and 3 months[6 weeks and 3 months] Length of hospital stay ‐ data collected from medical records[Postoperative period ‐ from immediately following the surgery to time of discharge under direct observation during inpatient stay, and reassessed again at 1 week via patient survey] Pain assessment 1‐week postoperative (daily VAS and analgesia use questionnaire for 3‐7 days) ‐ questionnaire designed specifically for this study[1 week post operative] Postoperative morphine equivalent dose rescue analgesia use ‐ data collected from medical records[In the first 24hours] Potential adverse effects of intravenous lignocaine ; ‐ Numbness around mouth/tongue ; ‐ Light‐headedness ; ‐ Ringing in ears ; ‐ Twitches ; ‐ Increased sedation ; ‐ Slurred speech ; ‐ Confusion ; ‐ Hallucinations ; ‐ Hypotension ; ‐ Bradycardia ; ‐ Other ; ; Data collected from medical records[Duration of the study ‐ for each participant follow up will continue until 3 months postoperatively] Psychological distress as measured by K10 score, Change from pre‐operative to 3 months postoperative[3 months post operative] Time to first breakthrough analgesic request ‐ data collected from medical records[24 hours postoperative] INCLUSION CRITERIA: ‐ Women requiring elective operative gynaecological laparoscopy for benign indication as determined and agreed by both the surgeon and the participant. ‐ Experience of pelvic pain on most days in the preceding 6 months ‐ Over 18years old and premenopausal at the time of the surgery. ‐ Participants who understand the conditions of the study and are willing to participate for the duration of study including all follow‐up. ‐ Participants who are capable of, and have given, informed consent to their participation in the study. ‐ English language or an available translator sufficient to complete the validated quality of life instruments. ‐ Surgery at Moorabbin Hospital under specialised Endosurgery unit

Actrn (2021). "Effect of Palmitoylethanolamide (PEA) and Resveratrol compared to a placebo on menstrual pain symptoms in an Adult Population – A double blind, randomised controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: PEA is a TGA approved ingredient for use in listed medicines in Australia (Brand name Levagen+). PEA + resveratrol (350 mg of Levagen+ (containing no less than 300 mg PEA) and 40 mg of Resveratrol) will be taken as a single capsule twice daily (one in the morning and one in the evening) with water from day 1 of first menstrual month until the end of the 3rd menstrual month. Participants will start to take trial product on day 1 of their next menstrual period following the baseline menstrual period. Once enrolled, participants will then undergo a health assessment including basic information, lifestyle, medication and medical history. Participants will document their use of any medication (including contraception use) including any use of medication during menses (i.e. pain medication, analgesics, NSAIDs) and complete a self‐reported Pittsburg Sleep Quality Index (PQSI) questionnaire. Following enrolment and health assessment, participants will be provided with their trial product, but instructed to only start supplementation at the required dose once they have recorded data for one full menstrual period. Participants will be provided with their supplements in an opaque bottle containing capsules according to their randomisation. Placebo capsules will appear identical to the active comparator. This study will consist of a total of 4 menstrual periods being recorded for each participant (1 without supplementation and 3 with supplementation). The first cycle will be recorded prior to any supplementation starting and will count as a baseline/control measure for each participant. Day 1 will be defined as the first day bleeding occurs. From day 1, participants will complete a visual analogue scale (VAS) and Menstrual Distress Questionnaire Form T (MDQ‐T) ass CONDITION: Alternative and Complementary Medicine ‐ Other alternative and complementary medicine Menstrual Pain; ; Menstrual Pain Reproductive Health and Childbirth ‐ Menstruation and menopause PRIMARY OUTCOME: Changes in monthly pain/severity as assessed by VAS for pain [Daily for the duration of each menstrual period ‐ Day 1 to end of menstrual cycle (Final day of 4th menstrual period primary endpoint)] INCLUSION CRITERIA: ‐ Women who experience mild to moderate menstruating pain ‐ Aged 18‐50 years old ‐ Otherwise healthy ‐ Able to provide informed consent ‐ Regular menstrual cycle (28 days ± 7 days) and period SECONDARY OUTCOME: Changes in menstrual symptoms (changes in pain) as measured by VAS scale. [Daily for the duration of each menstrual cycle ‐ Day 1 to end of menstrual cycle (Max 4 menstrual periods) ] Changes in menstrual symptoms as assessed by the MDQ‐T (change in menstrual symptom: bloating as assessed by the MDQ‐T) [Daily for the duration of each menstrual cycle ‐ Day 1 to end of menstrual cycle (Max 4 menstrual periods) ] Changes in premenstrual syndrome (PMS) severity as assessed by PMSIS [Day 1 of each menstrual cycle (4 menstrual periods) ] Changes in rescue medication use as assessed by self‐reported questions included in electronic capture of administered questionnaires (PMSIS, MDQ‐T). [Daily for the duration of each menstrual period ‐ Day 1 to end of menstrual cycle (Max 4 menstrual periods) ]

Actrn (2021). "Effect of Paracervical Block on Post-operative Pain Following Benign Laparoscopic Hysterectomy: objective Evaluation Of Parameters By Utilising A Single Centre Double Blind Randomized Controlled Trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Paracervical block with 0.5% Bupivacaine (with 1:200,000 Adrenaline) before benign laparoscopic hysterectomy The study will objectively evaluate pain by measuring opioid intake postoperatively and by determining the impact in patient reported pain beyond the first 24 hours postextubation. Subsequent impact on return to normal activity and quality of life score (QOL) will also be determined using the widely validated tool EQ‐5D 5L. Two‐arm single centre double blinded randomized placebo‐controlled trial. 1. Treatment arm: Paracervical injection of 0.5% bupivacaine with adrenaline 1:200,000 (20 mL) containing 100mg of anhydrous bupivacaine HCL and 100 micrograms of adrenaline. 2. Placebo arm: Paracervical injection of normal saline (20 mL) Cervical infiltration technique: Infiltration will be performed just prior the insertion of uterine manipulator by the primary surgeon. The content will be injected into the cervical stroma at the 3 and 9 o’clock positions with a depth of 2‐3 cm, with 10 mL injected at each side. Data will be routinely reviewed for completeness and accuracy as well as any evidence that may be indicative of participant risk. When the data are incomplete, attempts will be made to obtain the data whenever possible. Ensuring satisfactory response rate, data completeness and identifying missing data will remain responsibilities of the core research team. Every reasonable attempt will be made to determine the reason for a patient being lost to follow‐up. All participants will be given a standardised discharge prescription of twenty tablets of 5 mg Oxycodone for use as ‘PRN’. CONDITION: Anaesthesiology ‐ Pain management Pain; ; Pain Surgery ‐ Other surgery PRIMARY OUTCOME: ; a. Patient reported pain score at rest 60 minutes post‐extubation using Numeric Rate Scale (NRS) ; ; [1. 60 minutes post‐extubation ; ] SECONDARY OUTCOME: ; ; Patient reported pain score at rest and with coughing on the first post‐operative day using NRS ; ; ; [1. day 1: once, 24 hours post‐operation] Length of stay in hours (from the relevent electronic medical record)[From post extubation to discharge ] Opioid intake measurement by chart review: Use of oxycodone in day 1 and day 2[day 1 and day 2 post‐operation ] Opioid intake post‐discharge. This outcome will be assessed by conducting a phone interview on day 7 postoperative. Participants will be advised to keep a record of opioid intake at their discharge.[day 7 post‐operation ] Return to usual daily activity: Patient reported activity score on day 7 post‐op using EQ‐5D‐5L visual analogue scale [day 7 post‐operation] INCLUSION CRITERIA: 1. Age greater than or equal to 18 years 2. Undergoing a total laparoscopic hysterectomy for benign indications (elective) 3. Indication of prophylactic surgery for at‐risk patients can be included 4. With or without the following concurrent procedures: a. Unilateral or bilateral salpingo‐oophorectomy b. Excision of endometriosis (below pelvic brim)

Actrn (2021). "The effectiveness of a Mediterranean diet on hormonal, metabolic and body composition in overweight and obese women with Polycystic Ovary Syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Participants will be randomly allocated one of two prescribed and individualised 12‐week dietary interventions. The Mediterranean diet (MedDiet) group will be asked to consume a diet consistent with a traditional Mediterranean Diet including: 1–4 tablespoons of extra virgin olive oil/day 5–6 serves of vegetables/day 2–3 serves of fruit/day 4–6 serves of wholegrains/day up to 200ml red wine/day 3 serves of legumes/wk 3 serves of nuts/wk 3 serves of Greek yoghurt/wk 2‐3 servings of eggs/wk 2‐3 serves of fish and seafood/wk 1–3 servings of poultry/wk up to 1 serve of red meat/wk Participants will receive fortnightly face to face consultations with an Accredited Practising Dietitian at a consultation room at the University of the Sunshine Coast. Consultations will consist of: *Baseline lasting 60‐90mins to include assessment of outcome measures, counselling and education on the dietary protocol and a set of educational resources to facilitate dietary compliance *Five fortnightly consults at weeks 2, 4, 6, 8 and 10 lasting 30mins to include dietary counselling, education and monitoring of body mass. *Final lasting 60‐90mins to include assessment of outcomes. Participants will complete a daily dietary checklist consistent with the dietary protocol and return the checklist each fortnight. Participants will also complete a 4‐day food diary at baseline, week 6 and week 12. These will be used to facilitate discussion and education during the Dietetic consultations. In each of the five fortnightly consults, all participants (irrespective of the treatment allocation) will receive individual counselling and education by an Accredited Practising Dietitian. As such, part of this process will also involve the provisi CONDITION: Metabolic and Endocrine ‐ Other endocrine disorders Polycystic Ovary Syndrome; ; Polycystic Ovary Syndrome PRIMARY OUTCOME: Change in fasting blood glucose concentrations (12‐hour fasting blood test)[Baseline and post‐intervention (week 12)] Change in serum concentration of insulin (homeostatic model assessment (HOMA)) using 12‐hour fasting blood test.[Baseline and week 12 (post intervention)] Change in serum concentrations of total testosterone and sex hormone binding globulin (composite outcome) using 12‐hour fasting blood test.[Baseline and week 12 (post‐intervention)] INCLUSION CRITERIA: 1. Confirmed diagnosis of Polycystic Ovary Syndrome according to the Rotterdam criteria which is based on participants presenting with two of the three following criteria including: 1) menstrual irregularity (infrequent menstrual periods) and/or anovulation; 2) clinical and/or biochemical hyperandrogenism; 3) polycystic ovaries based on ultrasound examination. 2. Body mass index of 25kg/m2 or more SECONDARY OUTCOME: Adherence to a Mediterranean diet. This will will be assessed using the previously validated 14‐item MEDAS, used in the Prevención con Dieta Mediterránea (PREDIMED) study. The MEDAS determines adherence scores according to pre‐defined normative criterion cut‐off points for the habitual frequency of consumption or amount consumed (pre‐defined servings/day or servings/week) of 12 main dietary elements and two food habits related to a traditional MedDiet pattern. The 14 questions in the questionnaire will each be scored a 0 or 1, generating a maximum score of 14. Specifically, a MEDAS score greater than 10 suggests high adherence, scores between 6 and 9 indicate moderate adherence, and a score less than 5 is considered low adherence.[Baseline and post‐intervention (week 12)] Change in body mass (kg). A calibrated digital scale (AND Weighing; HW‐KGL, Melbourne, Australia) will be used to record body mass to the nearest 0.1 kg,[Change in body mass: Baseline, weeks 2, 4, 6, 8, 10, 12 (post intervention)] Change in waist circumference. This measure will be performed by trained research personnel and measured to the nearest 0.1 cm using a flexible steel tape measure (Lufkin Executive Thinline) at the point midway between the iliac crest and the lower cos l border (lower rib) according to standardized protocols. This will be measured on three separate occasions with the mean of the three measures used for final analyses.[Baseline and post‐intervention (week 12)] Dietary intake. this will be assessed using a 4‐day food record.Participants will be asked to record all food and beverage intake for a period of 4‐days (3 weekdays and 1 weekend day) using standard household utensils such as cup/teaspoon and tablespoon measures before sending the food record back to the investigators using the return paid envelope provided. All food records will be entered into Foodworks by a member of the research team for a comprehensive nutrient analysis assessment using food composition data derived from two Australian databases, AUSNUT 2007 and NUTTAB 2010. [Baseline, week 6 and week 12 (post intervention)] Feasibility to the MedDiet intervention. Participants randomized to the MedDiet intervention will complete an individual semi‐structured interview and complete a series of Likert scales to assess their opinion of the acceptability of the study resources and their confidence in their ability to follow a MedDiet. [Baseline and post‐intervention (week 12)] Physical activity status. This will be monitored using the short version of the International Physical Activity Questionnaire (IPAQ‐SF). IPA‐SF quantifies physical activity during the previous seven days and is divided into four categories: vigorous intensity, moderate intensity, walking and sedentary behaviour. Furthermore, intensity, frequency and duration of physical activity are also assessed.[Baseline and post‐intervention (week 12)]

Actrn (2021). "Efficacy and Demonstration of IntraVenous Iron for Anaemia in pregnancy (EDIVA)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This will be a two‐arm (1:1) Phase III open‐label superiority individual‐randomised controlled trial assessing the effectiveness of the intravenous iron ferric carboxymaltose in reducing maternal anaemia, compared to the standard of care of oral iron supplementation. Women in their second or third trimester of pregnancy will be screened for anaemia and those found to be moderately‐severely anaemic (haemoglobin <10g/dL) will be randomized to receive the intervention or the control. Intervention: intravenous iron treatment course administered once during pregnancy. Intravenous ferric carboxymaltose (FCM) 1000 mg total dose for body weight of 50 kg or more, or 20 mg/kg for body weight less than 50 kg, will be given over 15 minutes by a skilled study physician/ medical technologist. For participants receiving the intravenous iron treatment course: the skin will be cleaned with ethanol following standard aseptic procedure, and a sterile cannula will be inserted into the forearm or hand by a skilled study physician/medical technologist, and the cannula will be fixed in place with a sterile Tegaderm or clinical tape. The participant will be monitored over the 15 minutes of the infusion for any adverse events and at 10 minutes into the infusion, she will be asked if she experiences any problems and everything will be recorded. If the participant develops any complications, these will be attended to promptly and treated according to standard clinical management guidelines. The participant will be observed for a further 45 minutes and similarly, any problems experienced will be recorded. CONDITION: Anaemia;Iron deficiency;Maternal depression;Low birthweight;Prematurity;small for gestational age; ; Anaemia ; Iron deficiency ; Maternal depression ; Low birthweight ; Prematurity ; small for gestational age Blood ‐ Anaemia Diet and Nutrition ‐ Other diet and nutrition disorders Mental Health ‐ Depression Reproductive Health and Childbirth ‐ Fetal medicine and complications of pregnancy PRIMARY OUTCOME: Maternal anaemia (haemoglobin <11g/dL), assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[36 weeks gestation (this timepoint is after delivery of the intervention)] SECONDARY OUTCOME: Abortion (pregnancy loss before 28 weeks of gestation) as reported by participant, study staff or based on clinical records[<28 weeks gestation] Adverse perinatal events including postpartum haemorrhage, need for blood transfusion, intensive care admission or mortality, as reported by patient or based on clinical records, or as observed by study staff.[From recruitment to 28 days postpartum] Birthweight (as a continuous variable measured in grams) using infant scales[At delivery visit] Child neurodevelopment, assessed by neonatal behavioral assessment scale[At delivery and 42 days postnatal] Child neurodevelopment, assessed by the auditory brainstem response tool[42 days postnatal and 6 months postnatal] Child neurodevelopment, assessed by the Bayleys scales of infant development[6 months postnatal] Child physical growth (length and weight) as a composite outcome, measured using infant scales and measuring tape[42 days postnatal, 3 months postnatal and 6 months postnatal] Child physical growth (length, cm) measured with measuring tape[42 days postnatal, 3 months postnatal and 6 months postnatal] Gestational age at birth (weeks), based on calculated duration of gestation, using dating at baseline ultrasound examination to date of actual delivery.[At delivery visit] Infant adverse events including hospitalisation and clinic visits as reported by mother, study staff or based on clinical records[Throughout study from delivery through to 6 months old] Infant ferritin levels (continuous), assessed by enzyme‐linked immunosorbent assays (ELISAs) for serum ferritin.[42 days postnatal, 3 months postnatal and 6 months postnatal] Infant haemoglobin levels (as a continuous variable) assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[42 days postnatal, 3 months postnatal n 6 months postnatal] Infusion related adverse events including allergic reactions as reported by study staff or based on clinical records[Time of administration of intervention, and any severe adverse events reported by study staff or based on clinical records up to two weeks post intervention] Low birth weight (as a categorical variable, birth weight <2500g) using infant scales[At delivery visit] Maternal anaemia (haemoglobin <11g/dL), assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[4 weeks post intervention, 42 days postpartum, 3 months postpartum and 6 months postpartum] Maternal depression measured by the Edinburgh postnatal depression scale[4 weeks post intervention, 36 weeks gestation, and 3 months postpartum ] Maternal ferritin levels (as a continuous variable), assessed by enzyme‐linked immunosorbent assays (ELISAs) for serum ferritin.[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months postpartum and 6 months postpartum] Maternal haemoglobin levels (as a continuous variable), assessed by a finger prick test using a HemoCue301 portable haemolgobin analyzer[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months and 6 months postpartum] Maternal hypophosphatemia based on biochemical measurement of serum phosphate[4 weeks post intervention, 36 weeks gestation] Maternal inflammation, measured by enzyme‐linked immunosorbent assays (ELISAs) for C‐reactive protein[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months postpartum and 6 months postpartum] Maternal iron deficiency (ferritin <15 mg/L), assessed by enzyme‐linked immunosorbent assays (ELISAs) for serum ferritin.[4 weeks post intervention, 36 weeks gestation, 42 days postpartum, 3 months postpartum, 6 months postpartum] Mother to infant bonding measured by the mother to infant bonding scale [3 months postpartum] Neonatal mortality as reported by participant, study staff or based on clinical records[Death of child within the first month of life] Premature birth (<37 weeks) Gestational age at birth (weeks), based on calculated duration of gestation, using dating at baseline ultrasound examination to date of actual delivery.[At delivery visit] Small for gestation age as a dichotomous variable (<10th centile), based on baseline ultrasound dating of pregnancy adjusted birth weight[At delivery visit] Stillbirth (birth of a baby showing no signs of life after 28 weeks gestation) as reported by participant, study staff or based on clinical records[> 28 weeks gestation] INCLUSION CRITERIA: ‐ In their second (13‐25 completed weeks) or third trimester (26‐32 completed weeks of gestation), dated by Last Menstrual Period. ‐ Moderate to severe anaemia (capillary Hb <10g/dL). ‐ Not known to have a multiple pregnancy. ‐ Expected to deliver the baby inside or within 30 minutes of road transport of the study catchment area. ‐ Have drinking water groundwater iron <1mg/L. ‐ Willing to provide written informed consent (if the pregnant woman is <18 years of age, consent will be collected from her guardian, while she will sign an assent form).

Actrn (2021). "ENDOTEXT: a text message supportive program for individuals with endometriosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: ENDOTEXT is a text messaged based intervention that provides supportive messages to individuals living with endometriosis. Messaging covers a range of domains including general endometriosis information, lifestyle tips and self‐care. Participants will receive four semi‐personalised text messages (e.g., to their preferred name) per week, free of charge, for a period of three months with messages selected from the ENDOTEXT message bank according to their user characteristics (e.g., smoker vs. non‐smoker). Each message is very brief ‐ a maximum of 50 characters and should take less than 1 minute to read. CONDITION: Endometriosis;Quality of Life; ; Endometriosis ; Quality of Life Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders PRIMARY OUTCOME: Endometriosis‐specific quality of life assessed with the reliable and valid Endometriosis Health Profile Questionnaire‐30 (EHP‐30; Jones et al., 2006)[3 months post baseline] SECONDARY OUTCOME: Emotional health measured using the widely used and validated short‐version of the original DASS, the Depression, Anxiety and Stress Scales 21 item (DASS‐21; Lovibond & Lovibond[3 months post baseline] Self‐efficacy for managing endometriosis symptoms, daily activities, medication/treatment and social interactions, assessed by the reliable and valid PROMIS Self‐Efficacy for Managing Chronic Conditions Short‐Form 4‐item subscales (Cella et al., 2010; Lee et al., 2020). [3 months post baseline] The Perceived Consequences subscale of the valid and reliable Revised Illness Perception Questionnaire (IPQ‐R; Moss‐Morris et al., 2002) is a 6‐item measure which will be used to assess endometriosis severity[3 months post baseline] User acceptability (e.g., messages easy to understand) is assessed via a self‐report online survey using Likert‐type questions (i.e., along a scale from Not at all to Very Much so). These questions are derived from questions used in prior research by this team: ; Sherman KA, Shaw LK, Jørgensen L, Harcourt D, Cameron L, Boyages J, Elder E, Kirk J, Tucker K. Qualitatively understanding patients' and health professionals' experiences of the BRECONDA breast reconstruction decision aid. Psychooncology. 2017 Oct;26(10):1618‐1624. doi: 10.1002/pon.4346. Epub 2017 Jan 30. PMID: 27957772. ; and ; Singleton, A., Partridge, S., Raeside, R., Regimbal, M., Hyun, ; K., Chow, C., Sherman, K., Elder, E., Redfern, J. (2019). A text ; message intervention to support women's physical and mental ; health after breast cancer treatments (EMPOWER‐SMS): a ; randomised controlled trial protocol. BMC Cancer, 19(1), 1‐8. ; doi ="http://dx.doi.org/10.1186/s12885‐019‐5886‐8"[3 months post baseline] INCLUSION CRITERIA: Participants are eligible to participate if they are: over 18 years of age; clinically diagnosed with endometriosis; proficient in English; have access to the internet and a mobile phone; resident in Australia

Actrn (2021). "Enhancing treatment outcomes after gynaecological cancer (ACUMEN): using exercise to promote health after cancer therapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The total study period is 24 weeks. It comprises of a 12‐week exercise training intervention and a 12‐week maintenance period. After participant screening and baseline assessment, participants will be randomised to either the intervention or control group. Participants allocated to the control group will receive standard care and will receive general advice about self‐managed exercise, a Fitbit, and the Exercise is Medicine guidelines for gynaecological cancer. Control participants will be asked to wear the Fitbit device to assess physical activity performed over the study period. Participants assigned to the intervention group will received one‐on‐one supervision by an Accredited Exercise Physiologists or Physiotherapists (AEPP). Goals will be prioritised and set with the participant and the prescription co‐designed with the participant, including strategies for relapse prevention and longer‐term maintenance. As part of this process, the 12‐week exercise training intervention will adhere to the following principles: 1. Participants will be screened for known disease and risk of adverse events due to exercise with the Adult Pre‐Exercise Screening System (APSS). 2. The goal is to enhance neuromuscular strength, endurance, balance, flexibility, cardiorespiratory fitness and cardiovascular function. The AEPP will individually tailor exercise to the functional capacity of each participant towards these goals, cognisant of potential restrictions caused by surgical scarring, pain, metastases, lymphoedema, obesity, incontinence or neuropathic problems. 3. Participants will aim for 3 x 60 minute exercise sessions per week, individually prescribed by an Accredited Exercise Physiologist or Physiotherapist (AEPP) based on APSS results and the participan CONDITION: Cancer ‐ Cervical (cervix) Cancer ‐ Other cancer types Cancer ‐ Ovarian and primary peritoneal Cancer ‐ Womb (Uterine or endometrial cancer) Gynaecological cancer; ; Gynaecological cancer PRIMARY OUTCOME: ; The mean difference on the mental component summary (MCS) scores of health‐related quality of life between intervention and control in this trial, as measured by the SF36.; [; Baseline (pre‐intervention), week 12 (primary time‐point, end of intervention) and week 24 (longer‐term maintenance).; ] The mean difference on the physical component summary (PCS) scores of health‐related quality of life between intervention and control in this trial, as measured by the Short Form‐36 (SF36).[Baseline (pre‐intervention), week 12 (primary time‐point, end of intervention) and week 24 (longer‐term maintenance)] SECONDARY OUTCOME: Balance (assessed via centre of pressure displacement techniques) ; ] Duration of physical activity levels as assessed by the Fitbit watch.[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Dynamic upper and lower body muscle strength (chest and leg press respectively using one repetition maximum).[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Exercise self‐efficacy as measured by the Exercise Self‐efficacy Scale (ESES). [Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance). 3. Resident in Australia. 4. Have access to the internet. 5. Own, or have access to, a computer or tablet device. 6. Willing and able to comply with all study requirements, including intervention, timing and nature of required assessments. 7. Able to speak and read in English to ensure consent is informed and documentation of participant‐reported outcome measures can be adhered to. 8. Can provide voluntary written informed consent. ; [Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Blood markers for steroid hormone modulation ‐ follicle stimulating hormone[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Blood markers for steroid hormone modulation ‐ u einizing hormone[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Blood markers for steroid hormone modulation ‐ oestradiol[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Blood markers for steroid hormone modulation ‐ progesterone[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Blood markers of glycaemic modulation (assessed by HBA1c levels in blood). [Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Blood markers of inflammatory modulation (assessed by the levels of TNF‐a, IL‐2, IL1ß, IL‐6 and IL‐8 in blood).[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Body composition measured via waist‐hip ratio with a measuring tape according to WHO STEPwise Approach to Surveillance (STEPS) protocol for consistent measurement. .[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Cardiorespiratory fitness (VO2peak and exercise capacity) assessed during a graded cycling test with breath‐by‐breath gas analysis [Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance). ; ] Frequency of physical activity levels as assessed by the Fitbit watch.[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Intensity of physical activity levels as assessed by the Fitbit watch.[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] INCLUSION CRITERIA: 1. Women > 18 years diagnosed with cancer of the ovary, cervix, Fallopian tubes, placenta, endometrium, vagina or vulva in the previous 60 months, including early, recurrent, advanced or metastatic cancer. 2. > 1 month since end of intensive cancer treatment (including surgery, radiotherapy, chemotherapy). Supportive therapies such as bisphosphonate, pain medication and hormone replacement allowable.

Actrn (2021). "Evaluation of the "Living with Loss" program: an online perinatal bereavement program for psychological distress and emotional wellbeing of parents following perinatal loss." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This study is a randomised controlled trial evaluating the efficacy and acceptability of a self‐guided internet‐based (i.e. online) perinatal bereavement program ‐ 'Living with Loss' ‐ compared to usual care in improving the psychosocial and emotional wellbeing of parents following perinatal loss. The 'Living with Loss' online program consists of six modules featuring interactive activities, information, and a comic‐style storyline. Modules will take approximately 30 minutes each to complete, and are designed to be completed in any order over a period of six‐to‐eight weeks (i.e. one module recommended to be completed per week with an additional two weeks for revision). Using the software reporting function, the research team will be able to view incomplete modules and encourage participants to finish via an automated email system. The total duration of the study period including follow‐up will be six (6) months. This online perinatal bereavement program aims to support parents through their grief experience and focuses on enhancing and building adaptive coping strategies to help parents identify, tolerate, and gain more control over the regulation of their emotional experiences. This online program includes skills and strategies from several psychotherapeutic modalities (i.e. Cognitive Behavioural Therapy, Complicated Grief Therapy, Mindfulness, and Compassion‐focused therapy) with content specifically addressing the most commonly reported psychosocial difficulties experienced by parents after the death of their baby (e.g. understanding styles of grieving, managing worry and intense emotions, facing difficult conversations, returning to work, relationships and communication, planning for the future etc). This online program has been co‐developed and d CONDITION: Mental Health ‐ Depression psychological distress;stillbirth;grief;depression;perinatal loss;neonatal death ;bereavement; ; psychological distress ; stillbirth ; grief ; depression ; perinatal loss ; neonatal death; ; bereavement Reproductive Health and Childbirth ‐ Complications of newborn Reproductive Health and Childbirth ‐ Fetal medicine and complications of pregnancy PRIMARY OUTCOME: Psychological distress severity: Changes in score from baseline on the Kessler Psychological Distress 10‐item Scale (K10)[The primary outcome will be assessed in the control group at two timepoints: Week 9 (primary timepoint) and week 21. ; ; The primary outcome will be assessed in the intervention group at the following timepoints: once weekly during the eight‐week active study period (weeks 1‐8); 1 week after program completion (week 9 post‐intervention commencement, primary timepoint); at the 3‐month follow‐up (week 21 post‐intervention commencement), and at the 6‐month follow up (week 33 post‐intervention commencement).] SECONDARY OUTCOME: Anxiety severity: Change in scores from baseline on the Generalized Anxiety Disorder 7‐item Scale (GAD‐7)[The secondary outcome will be assessed in the control group at two timepoints: Week 9 and week 21. ; ; The secondary outcome will be assessed in the intervention group at the following timepoints: 1 week after program completion (week 9 post‐intervention commencement); at the 3‐month follow up (week 21 post intervention assessment); and at the 6‐month follow up (week 33 post‐intervention commencement).] Brief Grief Questionnaire (BGQ)‐ 5 item self‐report assessment of grief symptomology[The secondary outcome will be assessed in the intervention group at the 6‐month follow up (week 33 post‐intervention commencement).] Extent of distress and remorse after a healthcare decision: Change in scores from baseline on the Decisional Regret 5‐item Scale (DRS)[The secondary outcome will be assessed in the control group at two timepoints: Week 9 and week 21. ; ; The secondary outcome will be assessed in the intervention group at the following timepoints: 1 week after program completion (week 9 post‐intervention commencement); at the 3‐month follow up (week 2 ost intervention assessment); and at the 6‐month follow up (week 33 post‐intervention commencement).] Grief intensity: Change in scores from baseline on the Perinatal Grief Scale ‐ 33‐item Short Form (PGS‐SF) ; [The secondary outcome will be assessed in the control group at two timepoints: Week 9 and week 21. ; ; The secondary outcome will be assessed in the intervention group at the following timepoints: 1 week after program completion (week 9 post‐intervention commencement); at the 3‐month follow up (week 21 post intervention assessment); and at the 6‐month follow up (week 33 post‐intervention commencement).] Health‐related quality of life: Change in scores from baseline on the Assessment of Quality of Life 35‐item Scale (AQoL‐8D) [The secondary outcome will be assessed in the control and intervention group at week 9 (9 weeks post intervention commencement) and at the 3‐month follow up (21 weeks post intervention commencement).] Participant health service utilisation on the Health Service Utilisation 23‐item Scale (HSUS)[The secondary outcome will be assessed in the control and intervention group at week 9 (9 weeks post intervention commencement) and at the 3‐month follow up (21 weeks post intervention commencement).] Participants satisfaction of the intervention program on the Module Satisfaction Scale (MSS)[Once weekly during the eight‐week active study period (Weeks 1‐8).] Participants satisfaction of the intervention program on the Program Satisfaction Questionnaire (PSQ)[Post‐intervention (Week 9 post intervention commencement).] Perinatal depression severity: Change in scores from baseline on the Edinburgh Postnatal Depression 10‐item Scale (EPDS)[The secondary outcome will be assessed in the control group at two timepoints: Week 9 and week 21. ; ; The secondary outcome will be assessed in the intervention group at the following timepoints: 1 week after program completion (week 9 post‐intervention commencement); at the 3‐month follow up (week 21 post intervention assessment); and at the 6‐month follow up (week 33 post‐intervention commencement).] INCLUSION CRITERIA: Parents who have experienced a stillbirth or neonatal death in the last 2 years, and: ‐ Aged 18 years or older; ‐ Experienced a stillbirth or neonatal death within the past two years; ‐ Reside in Australia; ‐ Oral and written fluency in English language; ‐ Reliable access to a computer with internet connection; ‐ Willing to provide informed consent online.

Actrn (2021). "Investigating the efficacy of a pulmonary recruitment maneuver and closed drainage in reducing shoulder tip pain in women undergoing a total laparoscopic hysterectomy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Participants that meet the study exclusion inclusion criteria will be randomised into one of four study groups. Group A ‐ Participants will receive the combined treatment of closed drainage for 4 hours and the pulmonary recruitment maneuver. Group B ‐ Participants will receive the single treatment of closed drainage for 4 hours. Group C ‐ Participants will receive the single treatment of the pulmonary recruitment maneuver plus a sham drain. Group D ‐ Participants will receive the current standard of care (no treatment) plus a sham drain. The method of entry into the patient’s abdomen will be left to the discretion of the surgeon. The maximum number of ports allowed to complete the surgery will be four. Only one 10mm port will be allowed. Intraabdominal pressure during the surgical procedure should not exceed 15mmHg and the maximum flow rate should not exceed 40ml/min. Closed Drain method The drain will be administered by the surgeon. A 15cm Blakes drain will be inserted through one of the existing 5mm port sites at the end of the surgery if the patient is randomized to arm A or B of the study. The drain will be placed on low suction, sutured down at its proximal end and removed 4 hours later by the ward nurse. Patient’s randomized to arm C or D of the study will have a sham drain tube placed beneath a strip of sterile gauze taped to the skin, with no intraperitoneal or subcutaneous insertion and removed 4 hours later by the ward nurse. Documentation will be provided to ward staff to ensure awareness of the presence of the sham drain tube. Pulmonary recruitment maneuver The pulmonary recruitment maneuver will be administered by the anaesthetist. The pulmonary recruitment maneuver wi CONDITION: Musculoskeletal ‐ Other muscular and skeletal disorders Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders Shoulder Tip Pain; ; Shoulder Tip Pain Surgery ‐ Other surgery PRIMARY OUTCOME: Shoulder tip pain will be measured using the numberical / visual analogue scale, 24‐36 hours after the patient has had a total laparoscopic hysterectomy .[Recorded 24‐36 hours after total laparoscopic hysterectomy.] SECONDARY OUTCOME: Incidence of hospital readmission will be ascertained from hospital records, consulting room records and at the final study visit. ; [42 days from the intervention.] Incidence of intraoperative complications graded according to the Clavien Dindo classification. ; ; [At time of surgery] Incidence of post‐operative complications to 42 days graded according to the Clavien Dindo classification ; [Post‐operative complications up to 42 days post surgery.] Length of hospital stay will be ascertained from hospital records. ; [Up to 42 days from the intervention.] The patient will complete a QoR‐15 questionnaire to measure patient‐reported quality of recovery, 24‐36 hours after surgery, and again at 6 weeks post surgery. ; [24‐36 hours post‐surgery and at 6 weeks post surgery ; ] INCLUSION CRITERIA: 1. All women aged 18 years and over undergoing total laparoscopic hysterectomy 2. American Society of Anesthesilogists (ASA) Score 1 or 2 3. Undergoing a total laparascopic hysterectomy for one of the following conditions:‐ 1. Abnormal uterine bleeding. 2.Early stage uterine cancer 3.Atypical hyperplasia 4. Uterine fibroids where the uterine size should not exceed 10cm. 5. Risk reducing surgery

Actrn (2021). "Program for Perinatal Mental Health Promotion and Work-Life Balance." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The MAternal Mental Health in the WORKplace (MAMH@WORK) intervention will address maternal mental health and well‐being protection and promotion during late pregnancy, postpartum and return to work. More specifically, it will target women’s psychosocial adjustment and resilience during this life stage, while promoting several strategic skills: recognition of signals and symptoms of mental disorders; reduction of stigma against mental disorders; coping skills for stressful situations, with a special focus on e‐training of mindfulness; enhancement of help‐seeking efficacy; and strengthening of emotional and cognitive self‐regulation. Health education sessions will be conducted by trained psychologists and psychiatrists experienced in cognitive‐behavioural therapy‐based psychoeducation interventions, prevention and treatment of depression and anxiety disorders. The intervention will be either conducted on‐site (Instituto de Saúde Ambiental da Faculdade de Medicina da Universidade de Lisboa) or live streaming online. The format, setting and contents of the intervention will be fully defined after scoping literature reviews and Delphi technique, which will assure its adequacy as a short‐term and sustainable intervention. Still, the intervention is planned as follows (slight changes are anticipated as a consequence of the scoping literature reviews and Delphi technique for consensus‐building): ‐ Modules: mental health literacy, self‐ and perceived stigma towards mental illness, work‐life balance, early signs of mental disorders, mother‐child interaction and promotion of secure attachment, social support, information about biofeedback (including technical details about the wearable devices), and mindfulness concepts and exercises. ‐ Materials: a standard CONDITION: Anxiety;Postpartum depression;Postpartum blues;Child‐mother attachment;Child emotional self‐regulation;Child cognitive self‐control;Poor sleep;Postpartum bonding; ; Anxiety ; Postpartum depression ; Postpartum blues ; Child‐mother attachment ; Child emotional self‐regulation ; Child cognitive self‐control ; Poor sleep ; Postpartum bonding Mental Health ‐ Anxiety Mental Health ‐ Depression Mental Health ‐ Other mental health disorders Public Health ‐ Health promotion/education Reproductive Health and Childbirth ‐ Childbirth and postnatal care Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders PRIMARY OUTCOME: Child attachment security assessed using the Strange Situation Procedure (Ainsworth & Bell, 1970).[12 months postpartum] Postnatal depression, assessed using the Edinburgh Postnatal Depression Scale (Cox et al., 1987) for the three arms.[2 weeks postpartum, 5 months postpartum and 12 months postpartum (primary endpoint)] Postpartum bonding, assessed using the Postpartum Bonding Questionnaire (Brockington et al., 2006) for the three arms.[2 weeks postpartum, 5 months postpartum and 12 months postpartum (primary endpoint)] INCLUSION CRITERIA: Native Portuguese speakers or women living in Portugal for at least 5 years; intended pregnancy; primiparous, singleton pregnant women at the gestational age of 28‐30 weeks; aged 18‐40 years; employed; with access to a smartphone; and have had understood and signed the project’s informed consent form. SECONDARY OUTCOME: Child development assessed using the Schedule of Growing Skills II (Bellman et al, 2012).[5 months postpartum and 12 months postpartum] Participants’ mental health literacy assessed using the Mental Health Literacy Scale (O'Connor & Casey, 2015) at the study close‐out.[Baseline (28‐30 weeks gestation) and 12 months postpartum.] Presenteeism assessed using the World Health Organization’s Heath and Work Performance Questionnaire (Kessler et al, 2003) for the three arms.[12 months postpartum] Resilience assessed using the Connor‐Davidson Resilience Scale (Connor & Davidson, 2003).[Baseline (28‐30 weeks gestation), 29‐31 weeks gestation, 2 weeks postpartum, 5 months postpartum and 12 o ths postpartum] Sleep quality determined using app data from a wearable device (sleep analyzer). [Baseline (28‐30 weeks gestation), 29‐31 weeks gestation, 2 weeks postpartum, 5 months postpartum and 12 months postpartum]

Actrn (2022). "Effect of Yoga and Theta Healing on Symptoms of Primary Dysmenorrhea." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Yoga will be applied to Group 1 and Theta Healing® to Group 2 for 6 months with a researcher. Based on researcher training in practitioner yoga and ThetaHealing for Group 1 yoga program designed by researcher, for Group 2 ThetaHealing program designed by researcher, Group 1 will do yoga 2 days a week 40‐45 minutes, live online group classes, low level of intensity designed for healthy people by a researcher. The program has been prepared based on simple pregnancy yoga practices so that everyone can easily apply it. After the program 3. months and 6. months participants will check by questionnaire and scales. Group 2 will do ThetaHealing 2 days a week 15‐30 minutes live online individual interviews. ThetaHealing is a meditation to remove negative emotions. Negative feelings are determined by talking to the participant. Determined negative emotions are tried to be reduced through meditation. After the program 3. months and 6. months participants will check by questionnaire and scales.The researcher will make the intervention. The yoga and ThetaHealing program will be done online 2 days a week for 6 months.[ Online live platform ( live online at participant’s home or any place where the participant can easily perform )] CONDITION: Alternative and Complementary Medicine ‐ Other alternative and complementary medicine Alternative and Complementary Medicine ‐ Spiritual care Primary Dysmenorrhea; ; Primary Dysmenorrhea Reproductive Health and Childbirth ‐ Menstruation and menopause PRIMARY OUTCOME: Primary outcome 1: Evaluation of change in dysmenorrhea with yoga (composite outcome). Dysmenorrhea Affectation Scale (DAC) and Negative Mood Regulation Expectancies Scale (NMR) will be used. [Timepoint: 3rd and 6th months (primary time point) after randomization ] Primary outcome 3: Evaluation of change in dysmenorrhea with ThetaHealing (composite outcome). Dysmenorrhea Affectation Scale (DAC) and Negative Mood Regulation Expectancies Scale (NMR) will be used.[Timepoint: 3rd and 6th months (primary time point) after randomization ] SECONDARY OUTCOME: Nil[Nil] INCLUSION CRITERIA: primary dysmenorrhoea problem among midwifery students at a university's faculty of health sciences

Actrn (2022). "Effectiveness and cost-effectiveness of an electronic mindfulness-based intervention for maternal mental health in the peripartum: a randomised controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: A Mindfulness App will be available to the intervention group. The Mater Parent Lounge app is a perinatal mindfulness‐based app, co‐designed by women with a lived experience of perinatal mental illness, and clinicians with expertise in mindfulness. The content on the app will consist of 40 mindfulness podcasts, tailored to different stages in the pre‐ (second trimester) and post‐partum period (6 months after birth). Women will therefore take part in the study from 16 weeks gestation to 6 months postpartum (approximately 11 months in total, dependent on which gestation week participants' give birth). The content of the app has been co‐designed by a working group of clinicians, peer workers, and consumer advocates (women who have previous lived experiences of perinatal mental health issues). The podcasts brief (5‐10 minute) videos that take women through a range of mindfulness exercises, such as breathing exercises, visualisation, body scanning, guided interaction with baby, guided meditation and other grounding techniques. Acceptability of the content was determined by all members of the co‐design working group over a series of meetings. The app will notify women with suggestions of appropriate (pregnancy‐period specific) podcasts on a regular basis. Women may choose to watch the suggested podcasts, or search for other podcasts when they wish to utilise them. Women will be free to use these podcasts as often as they wish for the study period, and beyond. For the study period, they will be asked to utilise the app a minimum of once a week to determine its benefit. Click analytics will be used to measure the frequency of app use, and to determine which podcasts are the most used. Daily 'mood' data will also be collected from the app using a five point faces scal CONDITION: Mental Health ‐ Anxiety Mental Health ‐ Depression Mental Health ‐ Other mental health disorders Mental Health ‐ Psychosis and personality disorders Mental Health ‐ Schizophrenia Perinatal Mental Health; ; Perinatal Mental Health PRIMARY OUTCOME: Psychological distress (measured using the Edinburgh Postnatal Depression Scale).[Baseline (16 weeks gestation), Time 2 (28 weeks gestation), Time 3 (3 months postpartum), Time 4 (6 months postpartum ‐ primary endpoint).] INCLUSION CRITERIA: Women who are attending either the public or private maternity clinics at Mater Mothers Hospital in South Brisbane with English Proficiency SECONDARY OUTCOME: App satisfaction and feedback ; App satisfaction and participant feedback will be collected in focus group interviews. ; A portion of randomly selected intervention participants will be sent an invitation to participate in a focus group. Approximately 15 women will be recruited for focus group interviews, which will be conducted in groups of 6‐8. They will be facilitated by a member of the research team with experience in qualitative interviewing. ; The interviews will be conducted at the Mater hospital. Women will receive free parking and will be compensated with a $50 voucher for their time. ; Focus group interviews will be semi‐structured (based on an interview question guide), and will be approximately 45 ‐ 60 minutes in length. They will be audiotaped and then de‐identified and transcribed by a professional, third party transcription service. [Focus group interviews will be conducted at the conclusion of the study. ] App utilisation. Click analytics will be used to determine the frequency to which the app was used, and which podcasts were listed to most frequently. [This data will not be collected at a specific timepoint, but will be looked at periodically during the study period by researchers. ] Cost‐efficiency (cost benefits) of the intervention, assessed using Quality‐Adjusted Life Years (QALYs ‐ derived from the PROMIS Global‐10 quality of life survey).[Baseline (16 weeks gestation), Time 2 (28 weeks gestation), Time 3 (3 months postpartum), Time 4 (6 months postpartum).] Mother‐infant bonding (measured using the Mother‐to‐infant bonding sc e).[Time 3 (3 months postpartum), Time 4 (6 months postpartum).] Satisfaction with the mindfulness app, measured using a Satisfaction Survey. This is a study‐ survey developed specifically for the purposes of this research project.[Time 3 (3 months postpartum)]

Actrn (2022). "The Effects of Eurycoma Longifolia Water Extract (Physta®) on Well-Being of Peri and Postmenopausal Women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The study is a randomized, double‐blind, placebo‐controlled study 12 weeks study involving middle‐aged women from 45 to 55 years old. The study aim is to determine the effect of Tongkat Ali water extract (Physta®) on overall well‐being of peri and postmenopausal women. Eligible subjects will be selected and randomized into three study groups (A, B or C) to receive one supplement capsule daily, each containing either 50 mg or 100 mg of Tongkat Ali water extract (Physta®) or 280 mg of maltodextrin placebo respectively. Subjects will be required to attend 3 follow up visits (week 0 (baseline), week 6 and week 12) at the study site. Study compliance and adherence to protocol will be monitored by performing capsule counting and with reference to the daily dose diary filled up by the subjects (week 6 and week 12 visits). CONDITION: Alternative and Complementary Medicine ‐ Other alternative and complementary medicine Menopause ;Climacteric symptoms ; ; Menopause ; Climacteric symptoms Reproductive Health and Childbirth ‐ Menstruation and menopause PRIMARY OUTCOME: Energy measured using Chalder Fatigue Scale (CFQ) questionnaire ; [The trial is conducted for 12 weeks of oral administration of Tongkat Ali Physta supplement. ; At 4 timepoints the outcomes will be measured (Week 0 (Baseline), Week 2, Week 6 and Week 12).] Mood state by using Profile of Mood State (POMS) questionnaire; [The trial is conducted for 12 weeks of oral administration of Tongkat Ali Physta supplement. ; At 4 timepoints the outcomes will be measured (Week 0 (Baseline), Week 2, Week 6 and Week 12).] Quality of life by using Menopause‐Specific Quality of Life (MENQOL) questionnaire ; [The trial is conducted for 12 weeks of oral administration of Tongkat Ali Physta supplement. ; At 4 timepoints the outcomes will be measured (Week 0 (Baseline), Week 2, Week 6 and Week 12).] SECONDARY OUTCOME: Effects of the Eurycoma longifolia water extract (Physta®) on female reproductive hormones (estrogen, progesterone, Testosterone, luteinizing hormone (LH) and follicle‐stimulating hormone (FSH)). This is a composite secondary outcome. [For this secondary outcome measures, commercial blood tests will be performed at week 0, week 6 and week 12 to analyse the female reproductive hormones. ] Effects of the Eurycoma longifolia water extract (Physta®) on inflammatory biomarkers & oxidative stress biomarkers. Its a composite secondary outcome to measure the inflammatory biomarkers (iNOS, Cox2) and oxidative stress biomarkers (MDA, LPO). ; [For this secondary outcome measures, blood test will be done at week 0 and week 12. The plasma samples obtained from blood samples will be used to run the ELISA analysis to assess the respective inflammatory biomarkers (iNOS, Cox2) and oxidative stress biomarkers (MDA, LPO) of subjects. ] INCLUSION CRITERIA: a) Women aged 45‐55 years b) Scoring of MENQOL is more than or equal to 61 (higher score indicates the presence of climacteric symptoms) c) Experience aches at muscles, joints, back of the neck and head (Scores “YES” for MENQOL question number 12 or/and 15) d) Experience tiredness, worn out and lack of energy (Score “YES” for MENQOL question number 13 or/and 18) e) In a stable heterosexual relationship for at least 6 months f) BMI 20‐29.9 kg/m2

Actrn (2022). "Enhancing treatment outcomes after gynaecological cancer (ACUMEN For ALL): using telehealth exercise delivery to promote health after cancer therapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The total study period is 24 weeks. It comprises of a 12‐week exercise training intervention and a 12‐week maintenance period. After participant screening and baseline assessment, participants will be randomised to either the intervention or waitlist‐control group. Participants in the delayed intervention control group will complete a 12‐week control period, they will then be eligible for the intervention and the same outcome assessments will be repeated. The telehealth intervention has two components, an exercise component underpinned by a behavioural component. Both will be delivered via video‐link by an accredited exercise physiologist or physiotherapist (AEPP) trained in cancer care. The exercise component is structured over 12 weeks and adheres to Exercise and Sports Science Australia recommendations, including Adult Pre‐Exercise Screening System (APPS form) for risk of adverse event due to exercise. Goals will be prioritised and set, and the prescription co‐designed with the participant, including strategies for longer‐term maintenance. The intervention will adhere to ESSA guidelines: 1. The goal is to enhance neuromuscular strength, endurance, balance, flexibility, and cardiorespiratory fitness. The AEPP will individually tailor exercise to the functional capacity of each participant towards these goals, cognisant of participant restrictions. 2. Up to 3 X60‐minute exercise sessions per week, individually prescribed by an AEPP. The session will aim for an aerobic component (up to 40 minutes moderate‐to‐vigorous intensity based on a percentage range of age‐predicted heart rate maximum) such as jogging ‐on‐the‐spot or fast walking and resistance component (2 X8‐12+ repetitions of major muscle group exercises at >6‐10 on the OMNI percei CONDITION: Cancer ‐ Cervical (cervix) Cancer ‐ Other cancer types Cancer ‐ Ovarian and primary peritoneal Cancer ‐ Womb (Uterine or endometrial cancer) Gynaecological cancer; ; Gynaecological cancer PRIMARY OUTCOME: Feasibility of the exercise intervention delivered via video technology will be assessed as a composite outcome determined by percentage of patients who register interest and are recruited into the study via audit of study screening and enrolment logs.; Attendance at the scheduled exercise sessions will be recorded by the AEPP via intervention session sheets, capturing the participant attendance for each of the 36 planned sessions. ; Adherence and compliance with the exercise prescription (measured by heart rate monitoring and perceived exertion) will be recorded by the AEPP via intervention session sheets, capturing the participant heart‐rate response, perceived exertion rating, load and repetitions of every exercise for each of the 36 planned sessions. [Cumulative data will be assessed at the conclusion of the study.; ] Safety will be measured by data collected on adverse events.; Number, type and severity of adverse events reported. Participants will be advised that they should report any spontaneous adverse events that may occur during the study, and will be provided with contact details for reporting. AEPP will monitor and report adverse events during the intervention period, and participants will be regularly contacted during trial for monitoring of adverse events.; [Any adverse events that occur throughout the 24 weeks of the study will be recorded in the study adverse event log for cumulative review at the conclusion of the study.] SECONDARY OUTCOME: Adherence will be measured as the percentage of the prescription completed during these sessions, divided into modalities. Adherence and compliance with the exercise session will also be assessed through remote heart rate monitoring via a fitbit device. The number of non‐supervised home‐based sessions completed will also be recorded. Reasons for non‐adherence will also be captured. [Cumulative data will be assessed at the conclusion of the study.] Aerobic fitness (6 minute walk test) will assess the participant’s exercise capacity.[Baseline, week 1 and week 24.] Attendance will be measured as the number of video‐supervised sessions attended. The number of video‐supervised sessions attended by will be recorded via intervention session sheets completed for each individual session.[Cumulative data will be assessed at the conclusion of the study.] Balance (assessed via centre of pressure displacement techniques).[Baseline, week 12, and week 24.] Body composition measured via waist‐hip ratio with a measuring tape according to WHO STEPwise Approach to Surveillance (STEPS) protocol for consistent measurement. [Baseline, week 12, and week 24.] Duration of physical activity levels as assessed by the Fitbit watch.[Baseline, week 12, and week 24.] Dynamic lower body muscle strength (timed repetition test).[Baseline, week 12, and week 24.] Dynamic upper body muscle strength (timed repetition test).[Baseline, week 12, and week 24.] Exercise self‐efficacy as measured by the Exercise Self‐efficacy Scale (ESES)[Baseline (pre‐intervention), week 12 (end of intervention) and week 24 (longer‐term maintenance).] Frequency of physical activity levels as assessed by the Fitbit watch.[Baseline, week 12, and week 24.] Intensity of physical activity levels as assessed by the Fitbit watch.[Baseline, week 12, and week 24.] Participants perceived benefits and barriers to exercise as measured by the Exercise Benefits / Barriers Scale (EBBS).[Baseline, week 12, and week 24.] The mean difference on the mental component summary (MCS) scores of health‐related quality of life between intervention and control in this trial, as measured by the SF36.[Baseline, week 12, and week 24.] The mean difference on the physical component summary (PCS) scores of health‐related quality of life between intervention and control in this trial, as measured by the Short Form‐36 (SF36).[Baseline, week 12, and week 24.] The telehealth intervention will be assessed for its acceptability, appropriateness, and feasibility as a composite to determine the implementation potential of telehealth video collected via Acceptability, Appropriateness and Feasibility of Intervention Measures (AFFIMs) questionnaire. The AAFIMs collectively assess the factors that indicate implementation potential to patients, clinicians and organisational decision‐makers. Each measure contains four items that assess the extent to which respondents consider an intervention or implementation strategy is acceptable, appropriate, and feasible. Higher scores indicate greater acceptability, appropriateness, and feasibility. As a suite, the measures have confirmed validity and reliability.[Completed by AEPP and participant at the conclusion of the final intervention session.] INCLUSION CRITERIA: 1. Women aged 18 years or older diagnosed with cancer of the ovary, cervix, Fallopian tubes, placenta, endometrium, vagina or vulva in the previous 60 months, including early, recurrent, advanced or metastatic cancer. 2. > 1 month since end of intensive cancer treatment (including surgery, radiotherapy, chemotherapy). Supportive therapies such as bisphosphonate, pain medication and hormone replacement allowable. 3. Resident in Australia. 4. Have access to the internet. 5. Own, or have access to, a computer or mobile device. 6. Willing and able to comply with all study requirements, including intervention, timing and nature of required assessments. 7. Able to speak and read in English to ensure consent is informed and documentation of participant‐reported outcome measures can be adhered to. 8. Can provide voluntary written informed consent. 9. Unable or unwilling to attend face‐to‐face exercise training and objective outcome assessment

Actrn (2022). "High-Intensity Functional Training for Polycystic Ovary Syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group 1 ‐ High‐intensity functional training (HIFT) The HIFT intervention will be supervised by a certified fitness professional. HIFT will include both “cardio” or “resistance” sessions. The cardio sessions include body weight and dynamic movements which target the aerobic and anaerobic energy systems. The resistance sessions use weighted functional movement patterns to target muscle mass, strength, and power. Both the cardio and resistance sessions last a total of 45 minutes. Participants will initially be prescribed one exercise session per week (aerobic session) in week 1, two exercise sessions per week (1 aerobic sessions and 1 resistance session) in week 2. From week 3, participants will be asked to attend three HIFT (2 aerobic sessions and 1 resistance session) classes per week. Location where intervention will be delivered: F45® Bulli or Corrimal, Mode of delivery: the exercise sessions will be delivered in groups of no more than 30 people per class. Duration of intervention: 12 weeks. Intensity of duration: participants will be asked to work out at an intensity equivalent to 13‐17 RPE during the active exercise period. Examples of exercises prescribed as part of the intervention: squats (bodyweight and weighted back squats), deadlift, push‐press, medicine ball throws, skipping (including double‐unders) and more. Adherence: Adherence will be monitored through session attendance checklists and HR will be recorded by a HR monitor. Group 2 ‐ Physical Activity Guidelines (PAG) Participants in PAG will be prescribed an exercise program that is consistent with current Australian physical activity guidelines for 12 weeks. This includes instruction to undertake 150 min of moderate‐intensity or 75 min of vigorous‐intensity aerobic exer CONDITION: Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders Metabolic and Endocrine ‐ Other endocrine disorders Polycystic Ovary Syndrome; ; Polycystic Ovary Syndrome PRIMARY OUTCOME: Cardiorespiratory fitness assessed via graded exercise test and gas analysis.[Assessed at baseline and at 13 weeks post‐intervention commencement. ] Muscle endurance via maximal repetitions to failure at 70% 1RM for the bench press and back squat exercises.[Assessed at baseline and at 13 weeks post‐intervention commencement. ] Muscular strength assessed via one repetition maximum of chest press and leg press exercises.[Assessed at baseline and at 13 weeks post‐intervention commencement. ] INCLUSION CRITERIA: To participate in this study, participants must: • be between the ages of 18‐40 years; • have a diagnosis of polycystic ovary syndrome (PCOS) as per Rotterdam 2003 criteria; • be physically inactive (undertaking < 150 minutes of exercise per week or exercising < 3 days per week); • have overweight or obesity (BMI between 25 to 40 kg/m2); • able to attend three training sessions per week at F45® Bulli or Corrimal for 12 weeks; • ability to read and communicate in the English language. SECONDARY OUTCOME: Insulin sensitivity measured via homeostatic model of insulin resistance (HOMA‐IR) and oral glucose tolerance test.[Assessed at baseline and at 13 weeks post‐intervention commencement. ] Body composition (fat mass, lean mass, body fat %) will be assessed using dual x‐ray absorptiometry. [Assessed at baseline and at 13 weeks post‐intervention commencement. ] Anthropometry (body mass, height, waist circumference, hip circumference)[Assessed at baseline and at 13 weeks post‐intervention commencement. ] Arterial stiffness measured via pulse wave velocity assessment.[Assessed at baseline and at 13 weeks post‐intervention commencement. ] Blood biochemistry: serum glucose, insulin, lipids, inflammatory markers, and liver enzymes[Assessed at baseline and at 13 weeks post‐intervention commencement. ] Physical activity enjoyment scale (PACES Questionnaire) [Assessed at baseline and at 13 weeks post‐intervention commencement. ] Quality of life via 36‐Item Short Form Health Survey (SF36) and Mo fied Polycystic Ovary Syndrome Health‐Related Quality of Life Questionnaire (MPCOSQ)[Assessed at baseline and at 13 weeks post‐intervention commencement. ]

Actrn (2022). "The impact of electromyographic (EMG)-biofeedback assisted training on the function of the pelvic floor muscles in women after vaginal and cesarean delivery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Before starting the research, all participants will be assessed: strength and endurance of the pelvic floor muscles with the help of palpation, EMG and perineometer, bladder diary, UDI‐6 and IIQ‐7 questionnaire, SES Self‐assessment scale, changes in KHQ quality of life indicators and Questionnaire of the Quality of Women's Sexual Life. Randomized controlled trials will be carried out on a group of not less than 100 patients aged 25‐35 years, after the first vaginal delivery or after the first caesarean section, which will be randomly divided into groups: Arm 1: Vaginal delivery Bebo® group A group of women after vaginal delivery underwent a 6‐week, each session according to the Bebo® concept runs for one hour . The training is conducted individually, by a qualified therapist, twice a week. We will monitor attendance using the attendance list. The Bebo® concept ‐ is based on five exercise groups, which are: awareness exercises, mobilization exercises, strengthening exercises, relaxation exercises, and the integration of pelvic floor muscles in everyday activities. Each group of exercises will last approximately 10 minutes. Arm 2: Vaginal delivery Bebo®+ EMG group A group of women after vaginal delivery underwent a 6‐week, each session according to the Bebo® concept runs for one hour , supported by a 10‐minute EMG‐biofeedback training. The training is conducted individually, by a qualified therapist, twice a week. The group, apart from exercises according to the Bebo® concept, will perform a 10‐minute EMG‐biofeedback training. Its aim will be to obtain conscious tension of the pelvic floor muscles with a strength corresponding to 20, 50, 80% of the previously measured maximum contraction and to maintain the tension at th CONDITION: Caesarean section;Urinary incontinence;Pelvic floor dysfunction; ; Caesarean section ; Urinary incontinence ; Pelvic floor dysfunction Reproductive Health and Childbirth ‐ Childbirth and postnatal care PRIMARY OUTCOME: A perineometer is a device used to measure the resting tension [cmH2O], the maximum voluntary force of contraction [cmH2O] and the strength of the pelvic floor muscles [s]. The examined person places the probe into the vagina to a depth of 3.5 cm. The subject is asked to perform 3 contractions and hold them for 5 seconds, the pause between each contraction was 30 seconds.[The procedure will be performed at the start of the tests and after 6 weeks.] EMG‐test. The EMG is used to assess the function of the pelvic floor muscles. The test will be carried out using surface and vaginal electrodes. The first electrode will be placed on the lower abdomen and the second will be mounted on the vaginal probe. The test will be performed according to a protocol consisting of 5 activities:; 1.60‐second rest (before starting the test ‐ divided into 3 intervals: I‐5s, II‐5s, III‐50s).; 2. Five 2‐second phase contractions (fast movements), with a 10‐second interval in between.; 3. Five 10‐second tonic contractions, with a 10‐second rest in between.; 4. One 60‐second strength contraction.; 5.60‐second rest (after exercise).[The procedure will be performed at the start of the tests and after 6 weeks.] Muscle strength assessed by palpation. The examination consists in inserting the index finger into the vagina, after disinfecting the hands, wearing disposable gloves and applying the gel, as well as observing the perineum area. The strength of the pelvic floor muscles during vaginal palpation will be assessed according to the PERFECT scheme.[The procedure will be performed at the start of the tests and after 6 weeks.] INCLUSION CRITERIA: primipara single pregnancy proper course of pregnancy 6‐8 weeks after vaginal delivery or cesarean delivery correct body weight consent to participate in free research SECONDARY OUTCOME: Self‐assessment of the respondents on the basis of the SES Self‐Evaluation Scale by M. Rosenberg. This tool evaluates your self‐esteem.[The procedure will be performed at the start of the tests and after weeks.] Assessment of toilet habits and fluid intake using the bladder diary. The bladder diary was designed specifically for this study.[The procedure will be performed at the start of the tests and after 6 weeks. ; Each patient will be asked to complete the diary for 3 days at the start of the study and after 6 weeks. ] Assessment of the impact of urinary incontinence on daily activity using the Incontinence Impact Questionnaire, Short Form (IIQ‐7) [The procedure will be performed at the start of the tests and after 6 weeks.] Symptoms of urinary incontinence using the Urinary Distress Inventory, Short Form (UDI‐6)[The procedure will be performed at the start of the tests and after 6 weeks.] The quality of sexual life based on the Sexual Quality of Life Questionnaire Female‐ (SQoL‐F)[The procedure will be performed at the start of the tests and after 6 weeks.] Quality of life using the King's Health Questionnaire (KHQ questionnaire)[The procedure will be performed at the start of the tests and after 6 weeks.] a medical certificate confirming that there are no contraindications to participate in the research

Actrn (2022). "Partner Cohort Treatment Study (PACT study) for bacterial vaginosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The PACT study is a partner‐treatment study for monogamous couples who are in the LGBTQIA+ community, where one person has a vagina and is diagnosed with bacterial vaginosis (BV) and their partner, regardless of their genitals or their gender identity (excluding cisgender‐men). All couple will receive treatment, as outlined below. Initially, participants will be asked if they have any allergies or contraindications prior to determination of their treatment. Couples will be treated with the same regimen in most cases (with some exceptions, see below). If both partners have a vagina and can tolerate both first‐line medications: both will be randomised to one of two treatment groups: Group 1: Both receive oral metronidazole 400mg twice daily for 7 days Group 2: Both receive combination of oral metronidazole 400mg twice daily for 7 days AND clindamycin 2% cream intravaginally once a day at night for 7 nights If one or both partners cannot tolerate oral metronidazole or topical clindamycin cream, they will both receive treatment with the regimen that one/both can tolerate (i.e. both will receive oral metronidazole 400mg twice daily for 7 days, or both will receive topical clindamycin cream intravaginally once daily at night for 7 nights). Couples will be excluded from the primary analysis and not form part of the main evaluation group in the following circumstances: • Partner with a vagina who does not have BV and declines treatment; The couples will still be followed for 9 weeks and asked to self‐collect specimens and complete questionnaires. This sub‐group will be able to access treatment at a later time point if they request it. • Partner with a penis; The participant will receive oral metronidazole 400mg twice daily and t CONDITION: bacterial vaginosis; ; bacterial vaginosis Infection ‐ Other infectious diseases Renal and Urogenital ‐ Other renal and urogenital disorders Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders PRIMARY OUTCOME: Establish the effect of both treatment strategies on the genital microbiota of couples using genomic sequencing of genital swabs.[This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post‐treatment commencement. All specimens will be included.] The acceptability, tolerability and adherence to concurrent partner treatment (whole population) as a composite outcome.; Adherence and tolerability will be assessed by audit of participant questionnaire designed specifically for this study and to be filled‐out the day after treatment is expected to be completed (i.e. day 8). Acceptability will be assessed by audit of participation in the trial by partners of an index with bacterial vaginosis diagnosed ‐ i.e. proportion of index BV participants whose partners received treatment.; [Adherence tolerability and acceptability will be assessed at day 8 post‐intervention commencement] SECONDARY OUTCOME: 1) BV recurrence within 9 weeks of treatment in all study groups/populations. This will be assessed using vaginal smears provided each week by participants, which will undergo Nugent scoring by an experienced microscopist. Two sequential Nugent scores of 7‐10 will indicate BV. [Recurrence will be assessed weekly for 9 weeks post‐treatment commencement] 2) BV recurrence within 4 weeks of treatment in all study groups/populations. ; BV will be assessed using vaginal smears provided each week by participants, which will undergo Nugent scoring by an experienced microscopist. Two sequential Nugent scores of 7‐10 will indicate BV. [Recurrence will be assessed weekly for 4 weeks post‐treatment commencement] 3) BV recurrence within 9 weeks of treatment assessed separately (stratified) according to treatment regimen (Arm 1 and 2) ; BV will be assessed using vaginal smears provided each week by participants, which will undergo Nugent scoring by an experienced microscopist. Two sequential Nugent scores of 7‐10 will indicate BV. The two treatment arms will not be able to be directly compared but the fi ings will be used to generate recurrence rates and confidence intervals by treatment arm.[Recurrence will be assessed weekly for 9 weeks post‐treatment commencement] 4) The acceptability, tolerability and adherence will be assessed as a composite secondary outcome. The findings will be stratified by the two different treatment regimens in the principal study population (Arm 1 and 2). ; Adherence and tolerability will be assessed by audit of participant questionnaire administered the day after treatment is expected to be completed (i.e. day 8) ‐ this questionnaire has been designed for this study. ; ; Acceptability will be assessed by audit of participation in the trial by partners of an inde Xwith bacterial vaginosis diagnosed (e.g. proportion of inde XBV participants whose partners also received treatment). These data will be separately assessed according to treatment arm.[Adherence tolerability and acceptability will be assessed at day 8 post‐intervention commencement] 5) The effect of treatment on the genital microbiome of couples over 9 weeks, assessed by (stratified) the two different treatment regimens in the principal study population (Arm 1 and 2), using genomic sequencing of genital swabs. This outcome may not be statistically powered to directly compare the two arms, however the results will be separately analysed.[This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post‐treatment commencement. All specimens will be included.] 6) The effect of concurrent partner treatment on the oral microbiome of couples over 9 weeks (including oral specimens from both the inde Xwith BV at enrolment and partner), using genomic sequencing of saliva samples. [This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post‐treatment commencement. All oral specimens will be included.] 7) The effect of concurrent partner treatment on the gut microbiome of couples over 9 weeks (including specimens from both the inde Xwith BV at enrolment and partner), using genomic sequencing of rectal swabs. [This will be assessed at baseline, and day 8 as well as weekly for 9 weeks post‐treatment commencement. All rectal swab specimens will be included.] INCLUSION CRITERIA: Inde Xparticipants will be eligible if they are: i) Are diagnosed with BV ii) Aged 18 years to pre‐menopausal (i.e. not more than 12 consecutive months after the last menstrual period/menopause) iii) Have an partner who meets the study criteria iv) Sufficient English to understand study procedures v) Provide written informed consent and is willing to comply with study procedures vi) Able to complete study protocol requirements The partner will be eligible if they: i) Have an partner (the index) who has been diagnosed with BV (they do not need to have a BV diagnosis as well) ii) Are aged 18 years or older iii) For partners of an inde Xwho attended clinic: enrol within 3 business days of their partner being diagnosed with BV (or the inde Xagrees to waits before starting treatment so that couples are aligned with therapy) iv) For partners at home: return baseline procedures/screening packs to determine BV‐status if appli

Actrn (2022). "ROBOTIC PELVIC SURGERY (ROPES) I: robotic Extended Resection for Locally Advanced and Recurrent Pelvic Malignancy: an IDEAL 2B Prospective Study to Design a Phase III Randomised Controlled Trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This IDEAL 2B observational study will assess the current use of robotic assisted extended resection for locally advanced and recurrent pelvic malignancies. Patients being considered for a robotic approach with locally advanced or recurrent pelvic malignancy will be included in the study. This study is observational and so it will not change which treatment the patient receives. INDICATION: Locally advanced or recurrent pelvic cancer requiring extended resection PRIMARY OBJECTIVES: To determine the current case volume and current patient selection criteria of robotic assisted surgery for locally advanced or recurrent pelvic malignancy in expert centres. SECONDARY OBJECTIVES: 1. To obtain pilot outcome data including clinical, pathological and patient reported outcome measures (PROMS). 2. To assess feasibility and plan a future prospective phase III randomised controlled trial of robotic versus non robotic extended resection in locally advanced or recurrent pelvic cancer. TRIAL DESIGN: Observational IDEAL 2B prospective study OBSERVATIONAL STUDY ARMS: Cases: Robotic extended resection for locally advanced or recurrent pelvic malignancy Controls: Non‐robotic extended resection for locally advanced or recurrent pelvic malignancy For participants there will be no change to their treatment. Their data will be collected from medical records. They will be invited to participate in PROMS questionnaires at: 1. 7 days post operatively 2. 3 months 3. 6 months 4. One year Measures used will take approximately 30 minutes at each time point: Generic Measures: • EORTC QLQC30‐ This is a questionnaire specifically designed to assess the QOL of cancer patients. • QOR15‐ Quality of Recovery ‐ T CONDITION: Cancer ‐ Bladder Cancer ‐ Bowel ‐ Anal Cancer ‐ Bowel ‐ Back passage (rectum) or large bowel (colon) Cancer ‐ Cervical (cervix) Cancer ‐ Neuroendocrine tumour (NET) Cancer ‐ Prostate Cancer ‐ Sarcoma (also see 'Bone') ‐ soft tissue Cancer ‐ Womb (Uterine or endometrial cancer) Locally advanced pelvic malignancy;Recurrent pelvic malignancy; ; Locally advanced pelvic malignancy ; Recurrent pelvic malignancy PRIMARY OUTCOME: ; ; To determine the current case volume of robotic assisted surgery for locally advanced or recurrent pelvic malignancy in expert centres. This will be assessed by a study specific questionnaire and data will be entered onto redcap at participating sites. [This primary timepoint will be at the time of selection for surgery, i.e. at initial enrolment into the study. ] To determine current patient selection criteria of robotic assisted surgery for locally advanced or recurrent pelvic malignancy in expert centres. ; ; The surgical team will enter data on redcap based on a patient selection for robotic surgery questionnaire designed specifically for the study. [for the primary end point, it will be assessed at time of selection for surgery; ] ; ] QOR15‐ Quality of Recovery[7 days, 3 months, 6 months and 1 year post operatively ] INCLUSION CRITERIA: 1. Patients with locally advanced or recurrent pelvic malignancy requiring extended resection 2. Patients in expert centres where a robotic approach is offered to selected cases with locally advanced or recurrent pelvic malignancy SECONDARY OUTCOME: Abdominal wall integrity assessed clinically and radiologically at one year at outpatient visit and reviewing routine postoperative surveillance CT's for evidence of hernia ‐ site and symptomatic status will be recorded [1 year ] clinical ‐ length of stay (days) using data linkage to medical records[Measured on discharge from hospital ] Clinical outcome‐ estimated blood loss ‐ measured in mls from operative note [This will be recorded on the day of surgery at the end of the case using the operative details proforma.] clinical‐ pain score ‐ verbal numeric rating scale [day 1 and day 7 post operatively ] complications‐ scored using Clavien dindo system [30 days post‐operatively ] Disease free survival ‐ survival and recurrence will be recorded at 1 year post oper ively using data linkage to medical records[1 year ] EORTC QRQC30 will be used as a disease specific quality of life metric and administered as a questionnaire to patients [day 7, 3 months, 6 months and one year post operatively ] European Quality of Life‐5 Dimensions Questionnaire‐ EQ5D will be used to assess quality of life ‐ this metric can be used for health economic analysis [7 days/ 3 months/6 months/ 1 year post operatively ] Pathological Factors ‐ R0 resection and nodes using data linkage to medical records reviewing the pathology report and the operative note [at 30 days postoperatively ] Patient reported outcome measures ‐ EORTC QLQC30[7 days post operatively, 3 months, 6 months and One year

Actrn (2022). "TELE-CONNECT: telehealth Exercise for Continence After Gynaecological Cancer Treatment." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Pelvic floor muscle training (PFMT) + home exercise program + non‐exercise components. Pelvic floor muscle training (PFMT) intervention: 'What' The intervention: 8 x 30‐60 minute telehealth sessions over 16 weeks (e.g. at 1, 2, 4, 6, 8, 10, 13 & 16 weeks). The initial consultation will be 60 minutes, consultations 2 ‐ 7 will be 30 minutes and consultation 8 will be 45 minutes in order to provide all elements of the intervention at the appropriate time. 'Who' The provider: Physiotherapist with postgraduate training in pelvic floor physiotherapy. Per‐protocol study training: detailed study manual and training in study processes and procedures, designed specifically for this study, including: pelvic floor muscle (PFM) assessment and exercise instruction processes; instructions for teaching use of the biofeedback device (device name: 'femfit®'); biofeedback data export; practice video‐consultations to practice video‐consultation skills. In the 8 weeks before the first participant is enrolled, physiotherapists will undergo protocol training, using live face to face and online training, supplemented by supply of all required resources and standard operating protocols. During the study: regular meetings with the research team to review per‐protocol procedures to ensure adherence to standardised training protocols. 'How' Group or individual: Individual telehealth‐delivered instruction in PFMT. The woman will receive the telehealth and home exercise program in her home. The femfit’s® pre‐determined, starting level and exercise program will be used. The starting level may be modified and additional tailoring to each woman may also be recommended by the treating study physiotherapist based on assessment findings. Supervision: Individually‐supervise CONDITION: Cancer ‐ Cervical (cervix) Urinary incontinence;gynaecological cancer;Faecal incontinence; ; Urinary incontinence ; gynaecological cancer ; Faecal incontinence Cancer ‐ Womb (Uterine or endometrial cancer) Cancer ‐ Ovarian and primary peritoneal PRIMARY OUTCOME: Impact of urinary incontinence: the International Consultation on Incontinence ‐ Urinary Incontinence Short Form (ICIQ‐UI SF)[Baseline, and 17 (primary end‐point) and 52 weeks post‐randomisation] ; To estimate costs of pad use for incontinence we will collect details of ; ‐ disposable pads including brand name, cost and average number used via Table 1 of the Dowell Bryant Incontinence Cost Patients Index (DBICI) ; ‐ reusable incontinence underwear including brand and cost.[Baseline, 17 and 52 weeks post‐randomisation] Laundry associated with incontinence ; Collected from participants using a modified version of Table 3 of the DBICI [Baseline, 17 and 52 weeks post‐randomisation] Cost of physiotherapist’s time (intervention group only) ; The cost of physiotherapy services provided to each participant will be calculated. [17 weeks post‐randomisation (intervention group only)] Work productivity ; Information about paid employment or self‐employed, leave and job performance will be collected from participants via a custom‐built questionnaire[Baseline, 17 and 52 weeks post‐randomisation.] Cost of resources (intervention group only). SECONDARY OUTCOME: Number of leakage episodes: collected by the participant in a custom‐developed 7‐day Accident Diary. [Baseline, 17 and 52 weeks post‐randomisation] Time spent (days, hours, minutes) on vigorous physical activities in the past 7 days: International Physical Activity Questionnaire Short form last 7 days Self‐Administered Format.[Baseline, 17 and 52 weeks post‐randomisation] Bother of pelvic floor symptoms including stress urinary incontinence, urinary urgency and frequency, urge incontinence, dysuria, pelvic organ prolapse, obstructed defecation, faecal incontinence, and dyspareunia: Pelvic Floor Bother Questionnaire (PFBQ)[Baseline, 17 and 52 weeks post‐randomisation] Impact of any type of urinary incontinence on quality of life: International Consultation on Incontinence Questionnaire Lower rinary Tract Symptoms Quality of Life (ICIQ‐LUTSqol)[Baseline, and 17 and 52 weeks post‐randomisation] Cost of pads for bladder leakage. ; The cost of intervention resources provided to each intervention group participant will be calculated by the research team. Resources include the biofeedback devices and package of participant resources.[17 weeks post‐randomisation (intervention group only) ; ] Acceptance and use of technology: self‐reported custom‐built questionnaire modified from the Unified theory of acceptance and use of technology (UTAUT‐II) model[Baseline and 17 weeks post‐randomisation] Number of continence pads used: collected by the participant in a custom‐developed 7‐day Accident Diary. [Baseline, 17 and 52 weeks post‐randomisation] Self‐reported health‐related quality of life: EQ‐5D‐5L[Baseline, 17 and 52 weeks post‐randomisation] Health service use related to urinary incontinence ; Health professional appointments, surgeries, investigations, and medications relating to urinary incontinence will be collected from participants using Section 2 of the DBICI [Baseline, 17 and 52 weeks post‐randomisation] Time spent (days, hours, minutes) on moderate activities in the past 7 days: International Physical Activity Questionnaire Short form last 7 days Self‐Administered Format.[Baseline, 17 and 52 weeks post‐randomisation] Patient Global Impression of Change (PGIC) Global Rating of Change Scale: self‐reported in response to “Compared to your first assessment in this study (when you completed your baseline information 17 weeks ago) overall, how would you rate your bladder control now?"[17 and 52 weeks post‐randomisation] Time spent (days, hours, minutes) walking in the past 7 days: International Physical Activity Questionnaire Short form last 7 days Self‐Administered Format.[Baseline, 17 and 52 weeks post‐randomisation] Time spent (days, hours, minutes) sitting in the past 7 days: International Physical Activity Questionnaire Short form last 7 days Self‐Administered Format.[Baseline, 17 and 52 weeks post‐randomisation] INCLUSION CRITERIA: Women aged 18 years or more; following cancer treatment (with or without radiotherapy) for Stage I, II or III uterine, cervical or ovarian cancer or borderline ovarian tumour; have the ability to speak and read English sufficiently for purposes of the study; have primary cancer treatment completed at least 6 months ago; have self‐reported urinary incontinence (at least 1 episode per week for last 4 weeks); have received no physiotherapy‐supervised pelvic floor treatment for urinary incontinence since commencing cancer treatment; and have a home internet connection and a smartphone.

Actrn (2023). "An anchor in the storm: the effectiveness of a flexible perspective-taking intervention in supporting the transition to motherhood." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Mothers in the intervention group will be given access to online resources specifically designed for use in this study: (i) a brief web‐based informational video (approx. 7 mins) that begins with a psychoeducation component on flexible perspective taking (self‐as‐context, a component of Acceptance and Commitment Therapy [ACT]) and relevance to mothers of infants (from birth to 23 months), drawing on ACT methaphors for enhancing a transcndent sense of self; (ii) an audio‐guided experiential exercise on flexible perspective taking tailored to pregnant and new mothers (approx. 9 mins), which women will be encouraged to listen to and use to guide their own meditation practice; and (iii) a simple tip sheet (designed specifically for this study) summarising key points that will be made available to participants to download and print. Resource use will be monitored using website analytics. Particpants will have access to the resources for the full duration of the study and extending to 12 months from the time of enrolment. CONDITION: Mental Health ‐ Anxiety Mental Health ‐ Depression Mental Health ‐ Other mental health disorders Mental health among mothers of infants;Alcohol use in pregnancy; ; Mental health among mothers of infants ; Alcohol use in pregnancy Reproductive Health and Childbirth ‐ Childbirth and postnatal care PRIMARY OUTCOME: Anxiety symptoms, as measured using the Depression Anxiety Stress Scales[6 weeks and 4 months post expected date of delivery] Depressive symptoms, as measured using the Depression Anxiety Stress Scales[6 weeks and 4 months post expected date of delivery] Post‐traumatic stress symptoms, as measured using the Impact of Event Scale ‐ Revised[6 weeks and 4 months post expected date of delivery] SECONDARY OUTCOME: Acceptability of the intervention, as indicated by a series of items (Likert scales, open‐ended questions) developed for use in this study[6 weeks post expected date of delivery] Alcohol consumption as assessed using the Alcohol Use and Disorders Identification Test (AUDIT‐C)[6 weeks and 4 months post expected date of delivery] Birth satisfaction, as measured using the Perception of Labour and Delivery Scale[6 weeks post expected date of delivery] Breastfeeding satisfaction, as measured using the Maternal Breastfeeding Evaluation Scale[6 weeks and 4 months post expected date of delivery] Emotional availability, as assessed on the Emotional Availability ‐ Self‐Report[4 months post expected date of delivery] Feasibility of the intervention, as indicated by rate of participant recruitment and particpant retention (assessed via data from participant tracking database)[At study completion] Psychological flexibility, as measured using the CompACT[6 weeks and 4 months post expected date of delivery] Self‐as‐context, as measured using the Self‐As‐Context Scale[6 weeks and 4 months post expected date of delivery] Stress symptoms, as measured using the Depression Anxiety Stress Scales[6 weeks and 4 months post expected date of delivery] INCLUSION CRITERIA: Participants will be women aged 18 years and over, who are currently at least 20 weeks pregnant, and living in Australia or New Zealand.

Actrn (2023). "The Bugs & Bumps study: the effect of a smartphone app on diet quality in pregnancy to support maternal and child mental health-related outcomes." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Starting from week 26 of pregnancy until birth, women in the intervention group will receive a 10‐week gut health‐focused, smartphone‐delivered, prenatal dietary program (Bugs & Bumps). The Bugs & Bumps dietary intervention app delivers eight simple dietary education topics, encompassing 120 short Instagram‐style videos, over a total of 57:53 minutes. Each video is very brief (< 1 minute) and can be stopped and started at any time. Women are asked to use the app from week 26 of pregnancy through to when their babies are born. Participants will watch the videos at their own pace, and set their first goal within the first week of the program. The eight topics are: 1. Introduction to the app, 2. Food Safety, 3. What you eat (what your diet is made up of), 4. Education about eating for health and wellbeing, 5. Education about what your gut bugs do, 6. Eating for your gut bugs ‐ dietary advice based on the Australian Dietary Guidelines (ADG), 7. Activities for how to plate up meals and supercharge them with specific ingredients, and 8. Goal setting. The dietary advice in topic 6 is focused on ‘eating for their gut bugs’, which involves adhering to the ADG and increasing intakes of prebiotic foods and common fermented foods. The program capitalises on app‐based features that deliver with behaviour setting techniques such as: ‐ Goal setting and monitoring; ‐ Links to question / answer style content to address barriers and enablers to change; ‐ Automated dietary monitoring (i.e., completing the Short Diet Questionnaire tool) and feedback. Feedback is based on the scores from the dietary questionnaire. to help improve their diet qualty, This feedback was designed by two Accredited Practicing Dietitians and the study investigator. ‐ Demonstrati CONDITION: Diet and Nutrition ‐ Other diet and nutrition disorders Inflammatory and Immune System ‐ Normal development and function of the immune system Mental Health ‐ Anxiety Mental Health ‐ Depression Mental Health ‐ Studies of normal psychology, cognitive function and behaviour Oral and Gastrointestinal ‐ Normal oral and gastrointestinal development and function Poor prenatal diet quality;Poorer prenatal mental wellbeing;Disturbances in the prenatal vaginal microbiome;Disturbances in the maternal gut microbiome;Elevated inflammatory markers in pregnancy;Elevated child emotional behaviour problems;Developmental trajectory of the infant gut microbiome;Elevated inflammatory markers in infancy;Poorer child neurocognition;Poorer child temperament;Elevated respiratory health problems;Elevated allergies;Poorer pregnancy outcomes;Poorer infant diet quality; ; Poor prenatal diet quality ; Poorer prenatal mental wellbeing ; Disturbances in the prenatal vaginal microbiome ; Disturbances in the maternal gut microbiome ; Elevated inflammatory markers in pregnancy ; Elevated child emotional behaviour problems ; Developmental trajectory of the infant gut microbiome ; Elevated inflammatory markers in infancy ; Poorer child neurocognition ; Poorer child temperament ; Elevated respiratory health problems ; Elevated allergies ; Poorer pregnancy outcomes ; Poorer infant diet quality Reproductive Health and Childbirth ‐ Normal pregnancy SECONDARY OUTCOME: Between‐group change from baseline in butyrate producing capacity of maternal stool samples measured using metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline in Lachnospiraceae in maternal stool samples measured using metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline in P. copri in maternal stool samples measured using metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline in Ruminococcaceae in maternal stool samples measured using metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline in the alpha diversity of maternal stool samples measured u ng metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline in the beta diversity of maternal stool samples measured in stool using metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline in the differentially abundant taxa of maternal stool samples measured using metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline over time in maternal anxiety symptoms using scores on the Edinburgh Postnatal Depression Scale[ 5 weeks post‐intervention (31 weeks gestation) ; 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline over time in maternal depression symptoms using scores on the Edinburgh Postnatal Depression Scale[ 5 weeks post‐intervention (31 weeks gestation) ; 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline over time in maternal dietary intake of discretionary foods as measured using the SDQ‐gut dietary questionnaire[ 5 weeks post‐intervention (31 weeks gestation) ; 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline over time in maternal dietary intake of fermented food intakes as measured using the SDQ‐gut dietary questionnaire[ 5 weeks post‐intervention (31 weeks gestation) ; 10‐weeks post‐intervention (36‐weeks gestation) ; ] Between‐group change from baseline over time in maternal dietary intake of prebiotic‐containing food intakes as measured using the SDQ‐gut dietary questionnaire[ 5 weeks post‐intervention (31 weeks gestation) ; 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change from baseline over time in maternal dietary variety as measured using the SDQ‐gut dietary questionnaire[ 5 weeks post‐intervention (31 weeks gestation) ; 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group change sustained throughout the postnatal period in maternal anxiety symptoms using scores on the Edinburgh Depression Scale[ 1‐month post‐birth ; 9‐months post‐birth ; 12‐months post‐birth ; 18‐months post‐birth] Between‐group change sustained throughout the postnatal period in maternal depression symptoms using scores on the Edinburgh Depression Scale[ 1‐month post‐birth ; 9‐months post‐birth ; 12‐months post‐birth ; 18‐months post‐birth] Between‐group changes in maternal GlycA in measured in blood serum[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group difference over time in infant allergies as measured by the International Study of Asthma and Allergies in Childhood scale[ 18‐months of age] Between‐group difference over time in infant respiratory health as measured by the International Study of Asthma and Allergies in Childhood scale[ 18‐months of age] Between‐group difference over time in the alpha diversity of infant stool samples measured using metagenomic sequencing.[ 1‐week of age ; 4 weeks of age, ; 12 months of age] Between‐group difference over time in the beta diversity of infant stool samples measured using metagenomic sequencing.[ 1‐week of age] Between‐group difference over time in the differentially abundant taxa of infant stool samples measured using metagenomic sequencing.[ 1‐week of age] Between‐group difference over time in the functional pathways of infant stool samples measured using metagenomic sequencing.[ 1‐week of age] Between‐group difference over time in the microbiome maturation trajectory of infant stool samples measured using metagenomic sequencing.[ 1‐week of age] Between‐group differences in infant adaptive skills scores using the clinician assessed Bayley Scales of Infant and Toddler Development[ 18 months of age] Between‐group differences in infant cognitive scores using the clinician assessed Bayley Scales of Infant and Toddler Development[ 18 months of age] Between‐group differences in infant internalising and externalising behaviour pr lem scores as measured using the Child Behaviour Checklist[ 18 months of age] Between‐group differences in infant language scores using the clinician assessed Bayley Scales of Infant and Toddler Development[ 18 months of age] Between‐group differences in infant motor scores using the clinician assessed Bayley Scales of Infant and Toddler Development[ 18 months of age] Between‐group differences in infant social‐emotional scores using the clinician assessed Bayley Scales of Infant and Toddler Development[ 18 months of age] Between‐group differences in infant socio‐emotional behaviour scores as measured using the Brief Infant and Toddler Social Emotional Assessment at 12‐months[ 12 months of age] Between‐group differences in infant temperament scores as measured using the Revised Infant Temperament Questionnaire [ 9 months of age] Between‐group differences in maternal differential abundance in vaginal microbiome composition measured by metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group differences in maternal differential abundance in vaginal microbiome function measured by metagenomic sequencing.[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group differences in maternal urinary Hippurate measured by Nuclear Magnetic Resonance spectroscopy[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group differences in maternal urinary metabolites measured by Nuclear Magnetic Resonance spectroscopy[ 10‐weeks post‐intervention (36‐weeks gestation)] Between‐group differences of infant systemic inflammation measured as GlycA in Guthrie blood spots[ Birth] Caesarean section rates measured by self‐report during Birth and Infant Health questionnaire..[ Birth] Gestational diabetes measured by self‐report during eliciting of adverse events.[ Birth] Pre‐eclampsia measured by self‐report during eliciting of adverse events.[ Birth] Preterm birth measured by self‐report during Birth and Infant Health questionnaire.[ Birth] PRIMARY OUTCOME: Between‐group change from baseline over time in maternal diet quality as measured by the Simple Dietary Questionnaire ‐ Gut (SDQ‐gut) dietary questionnaire[ 10‐weeks post‐intervention start (36‐weeks gestation ‐ primary timepoint)] INCLUSION CRITERIA: • Are able to participate and attend the study visits on Ryrie St, Geelong • Are adults aged 18 years or older • Are currently pregnant and less than 26‐weeks’ gestation • Will be 26 weeks gestation by the 21st week of recruitment • Use a smartphone with internet access • Have capacity to provide informed consent and understand written and spoken English

Actrn (2023). "The effect of a single therapy of the temporomandibular joints on the pelvic floor muscles." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: In the experimental group, a one‐time therapy of the temporomandibular joints will be used. The therapy will consist of soft tissue mobilization techniques inside and outside the temporomandibular joints. External techniques will include 1‐minute compression on the trigger points, positional release and myofascial release within the temporal muscle and masseter muscle. Internal techniques will include coppression and relaxation of the pterygoid muscle and masseter muscle. The therapy will be performed by physiotherapist in the supine position of patient and will last approximately 15 minutes. The measurements will be performed before and after the therapy. CONDITION: Musculoskeletal ‐ Normal musculoskeletal and cartilage development and function Physical Medicine / Rehabilitation ‐ Physiotherapy urinary incontinence;temporomandibular joints dysfunction;pelvic floor muscles tone disorder; ; urinary incontinence ; temporomandibular joints dysfunction ; pelvic floor muscles tone disorder PRIMARY OUTCOME: Evaluation of the bioelectrical activity at rest and during volitional contractions of the pelvic floor muscles, using surface electromyography. Evaluation of the following muscles will be performed: pelvic floor muscles, masseter muscles, sternocleidomastoid muscles, trapezius dorsi descending and ascending parts. The results will be analyzed together, indicating muscle activity and the relationships between them.[In the experimental group: Baseline and after a 15‐minute therapy of the temporomandibular joints. ; In the control group: double measurement with a 15‐minute break between measurements, without intervention.] Pelvic floor muscle activity using transabdominal ultrasonography (USG).[In the experimental group: Baseline and after a 15‐minute therapy of the temporomandibular joints. ; In the control group: double measurement with a 15‐minute break between measurements, without intervention.] The composite outcome includingbody balance and load distribution using baropodometry platform during standing.[In the experimental group: Baseline and after a 15‐minute therapy of the temporomandibular joints. ; In the control group: double measurement with a 15‐minute break between measurements, without intervention.] SECONDARY OUTCOME: Assessment of the mobility of the cervical spine using a centimeter tape.[In the experimental group: Baseline and after a 15‐minute therapy of the temporomandibular joints. ; In the control group: double measurement with a 15‐minute break between measurements, without intervention.] Assessment of the mobility of the temporomandibular joints using a caliper.[In the experimental group: Baseline and after a 15‐minute therapy of the temporomandibular joints. ; In the control group: double measurement with a 15‐minute break between measurements, without intervention.] INCLUSION CRITERIA: ‐ nulliparous; ‐ no pregnancies or miscarriages; ‐ no reported dysfunctions in the genitourinary system; ‐ consent to participate in the study

Actrn (2023). "Examining the efficacy and acceptability of an internet-delivered pain management program for endometriosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The Endometriosis Pain Course is an internet‐delivered self‐management program. It is a psychological treatment based on cognitive behaviour therapy (CBT) principles adapted to address the impacts of endometriosis‐associated symptoms and difficulties, such as chronic pain, on women's daily functioning and wellbeing. The course consists of: (a) Five lessons released via the eCentreClinic participant portal over an 8‐week period. Each lesson is delivered individually and covers a different topic and introduces 1‐2 core CBT skills designed to promote self‐management, psychological wellbeing and quality of life. Lesson 1 (released in week 1) provides an introduction and overview of the course, psychoeducation on chronic pain, the pain system, and emotional wellbeing. Participants are encouraged to identify their symptoms (e.g., unhelpful thinking styles, physical symptoms, unhelpful coping strategies) as a home‐based exercise. Lesson 2 (released in week 2) provides psychoeducation on unhelpful thinking, particularly as it relates to chronic pain and introduces cognitive challenging skills. Participants are encouraged to practise thought challenging in the following two weeks. Lesson 3 (released in week 4) covers behavioural activation and relaxation strategies to manage mood and anxiety symptoms, and participants are provided with the resources to undertake activity scheduling as a home‐based task. Lesson 4 (released in week 5) introduces activity pacing to manage symptoms such as pain and fatigue, and graded exposure to manage anxiety and avoidance. Participants are encouraged to attempt activity pacing and/or graded exposure tasks as a home‐based task. Lesson 5 (released in week 7) provides information and strategies relating to relapse prevention. Participants CONDITION: Depression;Anxiety;Chronic Pain;Endometriosis; ; Depression ; Anxiety ; Chronic Pain ; Endometriosis Mental Health ‐ Anxiety Mental Health ‐ Depression Reproductive Health and Childbirth ‐ Menstruation and menopause Reproductive Health and Childbirth ‐ Other reproductive health and childbirth disorders INCLUSION CRITERIA: (a) Diagnosis of endometriosis by a medical professional and experiencing endometriosis‐associated chronic pain (b) Chronic pain has been assessed and is being managed by a healthcare physician (c) Endometriosis‐related chronic pain/symptoms are affecting (self‐reported) psychological wellbeing, impacting functioning, or causing the individual problems at work, socially, or in another important way (d) Aged 18 or over (e) Access to the internet and an internet‐connected device. PRIMARY OUTCOME: Generalised Anxiety Disorder ‐ 7 (GAD‐7) which is a self‐report measure of anxiety symptomatology.[Application prior to enrolment, pre‐treatment, mid‐treatment (4 weeks post‐treatment commencement), post‐treatment (9 weeks post‐treatment commencement, primary endpoint), 3‐months post‐treatment commencement.] Pain Disability Index 7‐Item (PDI) which is a self‐report measure assessing the impact of chronic pain on different life domains.[Application prior to enrolment, pre‐treatment, mid‐treatment (4 weeks post‐treatment commencement), post‐treatment (9 weeks post‐treatment commencement, primary endpoint), 3‐months post‐treatment commencement.] Patient Health Questionnaire ‐ 9 (PHQ‐9) which is a self‐report measure of depressive symptomatology.[Application prior to enrolment, pre‐treatment, mid‐treatment (4 weeks post‐treatment commencement), post‐treatment (9 weeks post‐treatment commencement, primary endpoint), 3‐months post‐treatment commencement.] SECONDARY OUTCOME: Endometriosis Health Profile 5‐Item (EHP‐5) which is a 5‐item short form measuring the health‐related quality of life in women with endometriosis. [Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] Endometriosis Health Profile Modular Questionnaire 23‐Item (EHP‐23) which is a 23‐item adjunct o the Endometriosis Health Profile Questionnaire measuring impact of endometriosis on work, relationships, and interactions with the healthcare system. [Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] Fear of Pain Questionnaire 9‐Item (FOPQ‐9) which is an abbreviated version of the original 30‐item questionnaire that measures participants’ expected fearfulness towards a range painful experiences.[Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] Pain Acceptance 8‐Item (CPAQ‐8) which is an 8‐item measure designed to get a sense of peoples’ adjustment to living with pain. [Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] Pain Catastrophising Scale 4‐Item (PCS‐4) which is an abbreviated version of the original 13‐item measure that assesses a participants’ thoughts and feelings when in pain.[Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] Pain Self Efficacy Questionnaire 2‐Item (PSEQ‐2) which is an abbreviated version of the original 10‐item measure which rates participants’ confidence in performing various daily activities despite pain. [Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] Tampa Scale of Kinesiophobia 4‐Item (TSK) which is an abbreviated version of the original 17‐item scale assessing fear of movement and re‐injury.[Pre‐treatment, post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.] The Treatment Satisfaction Questionnaire (TSQ) which is a purpose‐built measure to assess the acceptability of online treatment Courses and to measure participants’ satisfaction with treatment. [Post‐treatment (9 weeks post‐treatment commencement).] Wisconsin Brief Pain Questionnaire 4‐Item (WBPQ‐4) which is a widely used questionnaire measuring the nature of participants’ pain including location, severity, and responsiveness to pain medications. [Application prior to enrolment, pre‐treatment, mid‐treatment (4 weeks post‐treatment commencement), post‐treatment (9 weeks post‐treatment commencement), 3‐months post‐treatment commencement.]

Actrn (2023). "Mate whenua: follow up after early medical abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Self‐assessment method of follow up after early medical abortion ‐ using a low sensitivity urine pregnancy test at 3 weeks after taking medications (mifepristone). It takes 1‐2 minutes, can be performed at home, and will be followed up by telephone or text with health practitioner. CONDITION: early medical abortion; ; early medical abortion Reproductive Health and Childbirth ‐ Abortion PRIMARY OUTCOME: Lost to follow up, using audit of patient medical records[6 weeks after early medical abortion (EMA)] INCLUSION CRITERIA: Included are women having an early medical abortion at 10.0 weeks' pregnant or less, who provide informed consent. SECONDARY OUTCOME: Additional community prescription dispensed (categorised as antibiotics, painkillers, or other), audit of patient medical records ; [6 weeks after EMA] Additional health care visit (categorised as to abortion service, hospital emergency department or mental health service), audit of medical patient records ; [6 weeks after EMA] Additional investigations (categorised as blood test, pelvic ultrasound scan, or other), audit of patient medical records ; [6 weeks after EMA] Admission to intensive care unit or equivalent, audit of patient medical records[6 weeks after EMA] Contraception use, assessed by patient questionnaire, developed specifically for this study[12 months after EMA] Death[6 weeks after EMA] ectopic pregnancy (categorised as ruptured or not), audit of patient medical records[6 weeks after EMA] Gestational age in weeks at detection of ongoing pregnancy, audit of patient medical records[8 months after EMA] Haemorrhage, defined as estimated blood loss 500mL or more (categorised as requiring red blood cell transfusion or not), audit of patient medical records ; [6 weeks after EMA] Health care utilisation cost, using the dataset, and basing it on pharmaceutical, equipment and consumable costs, and health care utilisation cost ; [at end of trial] Hospitalisation, audit of patient medical records[6 weeks after EMA] Incomplete abortion/retained pregnancy tissue/retained products of conception, audit of patient medical records[6 weeks after EMA] Incremental cost effective ratio for lost to follow up (LFU) rate, using the dataset[at end of trial] length of stay in intensive care, audit of patient medical records[6 weeks after EMA] number of additional health care visits, audit of patient medical records [6 weeks after EMA] number of additional investigations, audit of medical patient records[6 weeks after EMA] number of additional prescriptions, audit of patient medical records [6 weeks after EMA] Ongoing viable (live) pregnancy, using audit of patient medical records ; [up to 8 months after EMA] outcome of ongoing pregnancy (categorised as live birth, stillbirth, miscarriage, ectopic pregnancy, surgical abortion, medical abortion), audit of patient medical records [8 months after EMA] Patient experience, assessed by questionnaire developed specifically for this study, based on published similar patient experience questionnaires[6 weeks after EMA] Pregnancy outcome (e.g. miscarriage, abortion, birth), assessed by patient questionnaire, developed specifically for this study[12 months after EMA] Pregnancy, assessed by patient questionnaire, developed specifically for this study[12 months after EMA] primary reason for admission to intensive care, audit of patient medical records[6 weeks after EMA] Seen the primary care health practitioner (if yes, main reason), assessed by patient questionnaire developed specifically for this study[12 months after EMA] Staff satisfaction, assessed by questionnaire developed specifically for this study, based on published similar staff satisfaction questionnaires[6 months into recruitment] Successful abortion, defined as termination of pregnancy without need for surgery, audit of patient medical records[6 weeks after EMA] Surgical intervention, audit of patient medical records ; [6 weeks after EMA] timing of follow up test, using audit of patient medical records[6 weeks after EMA] type of additional surgical inte ention, audit of medical patient records[6 weeks after EMA] Uterine infection, defined clinically as fever, tachycardia, tender on exam, or purulent vaginal discharge AND received broad spectrum intravenous antibiotics, audit of patient medical records[6 weeks after EMA] Uterine rupture, defined as clinically significant rupture involving the full thickness of the uterine wall and requiring surgical repair, audit of patient medical records[6 weeks after EMA]

Ádám, C., et al. (2023). "Comparison of robot-assisted versus conventional laparoscopy for the treatment of endometriosis: a systematic review and meta‑analysis."
	
Adam, C., et al. (2022). "Investigating the most effective medical treatments for endometriosis-related pain: a systematic review and network meta-analysis."
	
Adam, N., et al. (2021). "Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) for metastatic ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma: a systematic review by the UK PIPAC Collaborative."
	
Adam, P., et al. (2021). "High-frequency, high-intensity transcutaneous electrical nerve stimulation (TENS) for postoperative pain after gynaecological surgery: a systematic review and meta-analysis."
	
Adams, J. A. M., et al. (2023). "The First Large GWAS Meta-Analysis for Postpartum Depression." The American Journal of Psychiatry 180(12): 862-864.
	
Adamyan, L., et al. (2023). "Laser vaporization compared with other surgical techniques in women with ovarian endometrioma: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 308(2): 413-425.
	Objective: To compare outcomes after laparoscopic cystectomy versus laser vaporization in women of reproductive age with ovarian endometrioma.; Evidence Review: Our systematic review and meta-analysis was registered in PROSPERO (CRD42021281781) and was done according to the PRISMA 2020 checklist. Studies (published until October 2021) were identified by searching PubMed, Cochrane Library, Google Scholar, and ClinicalTrials.gov databases (key words "cystectomy", "laser vaporization", and "endometrioma"). The search was conducted independently by two investigators (L.P. and S.I.). Inclusion criteria were: women of reproductive age undergoing surgery for symptomatic endometriomas larger than 30 mm. The exclusion criteria were: women who undergo conservative treatment. Outcomes were: risk ratio for recurrence, ovarian reserve and pregnancy rates. The studies included were randomized clinical trials (RCTs) and nonrandomized clinical trials (prospective controlled, prospective cohort, retrospective studies, and other types of studies) that included a minimum of 10 patients and written in English. Tools recommended by the Cochrane Society achieved risk-of-bias assessment.; Results: Totally, 874 studies were found, 9 studies were included in qualitative synthesis (822 patients). All the authors compared the efficacy and safety of cystectomy or laser vaporization in reproductive-aged women with ovarian endometrioma. The overall risk of bias for the randomized trials was 80% 'some concerns' and 20% 'low', and for the cohort studies, 50% 'some concerns' and 50% 'low'. The primary meta-analysis focused on recurrence rates (4 studies included) with no statistically significant differences found between these two interventions (RR = 0.53, 95% CI 0.24 to 1.21, P = 0.13). The next meta-analysis estimated antral follicle count (3 studies) which was significantly lower in cystectomy group (RR = - 2.56, 95% CI - 3.71 to - 1.42, P < 0.0001). Pregnancy rates were analyzed in 3 studies with no statistically significant difference (RR = 0.96, 95% CI 0.81 to 1.14, P = 0.64).; Conclusions: There was no statistical difference in the recurrence rate and pregnancy rates, but the antral follicle count was higher in the laser vaporization group. However, we need more clinical trials to make stronger recommendations. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Adel-Mehraban Mohammad, S., et al. (2022). "Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial." Complementary Therapies in Clinical Practice 46: 101544.
	Background: Menopausal symptoms have negative effects on the aspects of quality of life and impose a high cost on the health system. In traditional Persian medicine, pomegranate is recommended to alleviate menopausal symptoms.; Material and Methods: A randomized double-blind placebo-controlled trial was performed among 78 healthy women. Participants were interviewed three times: Before receiving the supplement/placebo, after completing the treatment, and after 3 weeks with no intervention. They filled out the demographic information sheet, modified-Kupperman index, and Menopause-Specific Quality of Life (MENQOL) questionnaires.; Results: The mean scores of the modified-Kupperman index and MENQOL characteristics before and after the treatment and after the follow-up period were significantly different between pomegranate and placebo groups in both modified-Kupperman and MENQOL scores (p < 0.001).; Conclusion: This study demonstrated that 4 weeks' treatment with the pomegranate supplement significantly ameliorates the irritating symptoms of menopause and improves the quality of life in menopausal women even after 4 weeks' medicine deprivation. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Adriana, G.-L., et al. (2023). "The impact of targeted endometriosis treatment on patients with central sensitization: a systematic review."
	
Adrianto, N., et al. (2024). "Perioperative vaginal misoprostol versus intraoperative pericervical hemostatic tourniquet outcome during abdominal myomectomy: A systematic review and meta-analysis." Journal of Endometriosis and Pelvic Pain Disorders.
	Background: Abdominal myomectomy is a commonly performed surgical procedure for removing fibroids. Various techniques and interventions have been explored to minimize blood loss during abdominal myomectomy. This study aims to assess and compare the efficacy of perioperative vaginal misoprostol and intraoperative pericervical hemostatic tourniquet in minimizing blood loss during abdominal myomectomy. Method(s): Eligible studies were identified using several databases. Analysis was conducted using RevMan version 5.3. This systematic review and meta-analysis were registered in PROSPERO on June 20, 2023, with registration number CRD42023434191. We included three studies with 88 participants. Result(s): Of the 73 records identified initially, 3 met the inclusion criteria-sample sizes of the included studies involving 88 participants. There was a significant mean difference in intraoperative blood loss (p = 0.022 (95% CI, 0.0706-0.901) and operative time (p = 0.015, 95% CI, 0.116-1.066) between groups. There was no significant mean difference in postoperative hematocrit (p = 0.053 (95% CI, -0.734 to 0.00411)) and intraoperative blood transfusion (OR = 1.60 (95% CI, 0.587-4.405), p = 0.355)) between group. Conclusion(s): Our studies indicate that using tourniquets lowered intraoperative bleeding and shortened operating time among the participants. Intraoperative vaginal misoprostol has no significant advantage over the tourniquet group in either intraoperative blood transfusion needs or postoperative hematocrit.Copyright © The Author(s) 2024.

Afandak, F., et al. (2023). "Effect of sumac powder on clinical symptoms, hyperandrogenism, inflammation, blood glucose, lipid profiles in women with polycystic ovary syndrome: A double-blind randomized clinical trial." Phytotherapy research : PTR 37(6): 2315-2325.
	Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders associated with a high risk of diabetes, atherosclerosis, and cardiovascular disease. The purpose of this study was to determine the effect of sumac powder on clinical symptoms and laboratory parameters in women with PCOS. The double-blind randomized controlled clinical trial was conducted on 88 women with PCOS randomly assigned to the intervention and control groups. The intervention group received three capsules each containing 1 g of sumac powder for 12 weeks. All data and serum levels of sex hormone, hs-CRP, glucose, and lipid profiles were measured at the baseline and at the end of the study. Data were analyzed using SPSS version 25 software. The ANCOVA test results showed that hs-CRP level was significantly reduced in the intervention group (p = .008). Blood glucose and lipid profiles in the intervention group were significantly reduced compared to the placebo group (p < .05). Insulin sensitivity and HDL levels were increased significantly in the Sumac group after the intervention (p < .05). Sumac powder can reduce the inflammatory effects, and glycemic status and lipid profile of polycystic ovaries in affected women, but has no significant effect on anthropometric parameters and sex hormones. (© 2023 John Wiley & Sons Ltd.)

Afghan, M., et al. (2022). "The Effect of Eight Weeks of Moderate-Intensity Continious Training on P- and QT Dispersion in ECG of Women with Polycystic Ovary Syndrome." Research in medicine: journal of research in medical sciences 46(4): 91‐98.
	
Aftan, R. M., et al. (2023). "A Comparison between the Effects of Evening Primrose Oil and Soybean Oil on Menopause Symptoms." Journal of Babol University of Medical Sciences 25(1): 305‐315.
	Background and Objective: More than 80% of women experience physical, vasomotor, sexual and psychological symptoms after menopause, and in 10‐20% of women, the severity of menopause symptoms affects their quality of life. Due to the complications of using chemical drugs, this study was conducted to compare the effectiveness of evening primrose oil and soybean oil in postmenopausal women. Methods: In this randomized controlled prospective study, 40 postmenopausal women were assigned into two groups of 20, 500 mg of evening primrose oil and 233 mg of soybean oil extract twice a day for 8 weeks. Measurement of serum hormones (follicle stimulating hormone, luteinizing hormone, estradiol), lipid profile, fasting blood glucose, and high sensitivity C‐reactive protein were performed. Moreover, menopausal symptoms were analyzed and compared based on the evaluation score of menopausal symptoms (range 0‐3). Findings: The mean age of women was (51.65±3.7) years. After 2 months of treatment with evening primrose oil, there was a decrease in follicle stimulating hormone, luteinizing hormone levels concurred with increase in estradiol levels (‐10.64%) (‐8.09%) (7.47%), respectively (p<0.05). Meanwhile, women receiving the soybean oil revealed increase in all the three hormones (5.77%) (12.73%) (13.39%), respectively (p<0.05). Total cholesterol and triglycerides decreased in both study groups after treatment (p<0.05), fasting blood glucose level decreased in group 1 only (‐1.39%), and high sensitivity C‐reactive protein decreased in group 2 only (‐22.33%) (p<0.05). In both groups, women presented with mild to moderate pre‐treatment menopausal symptoms (Menopause Symptom Assessment score ranging from 0.75 to 2.25) showed significant decrease in their score up to no symptoms in each study group after 2 months (less than 0.75) (p<0.01). Conclusion: The results of the study showed that both evening primrose oil and soybean oil supplements improve menopausal symptoms.

Agacayak, E., et al. (2022). "Comparison of long-term results of obliterative colpocleisis and reconstructive vaginal surgery including sacrospinous ligament fixation in patients with total genital prolapse." Nigerian journal of clinical practice 25(5): 597-604.
	Background: Treatment of total genital prolapse in elderly patients is still controversial in terms of postoperative objective and subjective results.; Aim: The present study aimed to compare the long-term objective and subjective cure rates of sacrospinous ligament fixation and Le Fort operation for treatment of total genital prolapse.; Patients and Methods: Patients over the age of 60 with stage 3 or 4 pelvic organ prolapse that presented to the Obstetrics and Gynaecology Clinic of the Faculty of Medicine of *** University. The study sample consisted of 17 patients that underwent Le Fort operation and 29 patients that underwent sacrospinous ligament fixation. Data on duration of operation, intraoperative complications, duration of hospital stay, and differences between preoperative and postoperative estimated blood loss, postoperative complications, and relapse in the long term were obtained. Questionnaires exploring quality of life, incontinence, and pelvic floor disorders were applied to the patients.; Results: As subjective cure rates, postoperative patient satisfaction (P = 0.001), regret rate (P = 0.038) and recommendation rate (P = 0.044), as well as postoperative questionnaire results, Pelvic Floor Impact Questionnaire and SF36 were found to be significantly better in the Le Fort group (respectively P = 0.039 and 0.042). As objective cure rates, there was no difference between the two groups in terms of postoperative cystocele, rectocele, and cystorectocele (P = 0.955) and postoperative recurrence of prolapse beyond the hymen (P: 0.893). Duration of operation and duration of hospital stay were found to be significantly shorter in the Le Fort group (respectively P = 0.032 and 0.012).; Conclusion: Le Fort operation could be the intervention of choice in sexually inactive elderly patients with stage 3 or 4 pelvic organ prolapse.; Competing Interests: None

Agarwal, D. and P. Chaudhary (2023). "Effect of Turmeric-Boswellia-Sesame Formulation in Menstrual Cramp Pain Associated with Primary Dysmenorrhea-A Double-Blind, Randomized, Placebo-Controlled Study." Journal of Clinical Medicine 12(12).
	Primary dysmenorrhea is a common menstrual disorder that significantly impacts women's quality of life, productivity, and healthcare utilization. In this randomized, double-blinded, placebo-controlled trial, sixty women with primary dysmenorrhea were randomly divided into two groups with thirty participants each, and were allocated either turmeric-boswellia-sesame formulation (treatment) or placebo. The participants were advised to take two softgels of 500 mg as a single dose of allocated study intervention (total dose 1000 mg) when their menstrual pain reached 5 or more on a numerical rating scale (NRS). Menstrual cramp pain intensity and relief were evaluated every 30 min post-dose until 6 h. Results indicated a promising role of turmeric-boswellia-sesame formulation for menstrual pain relief compared to the placebo. The mean total pain relief (TOTPAR) of the treatment group (18.9 ± 0.56) was found to be 12.6 times better than the placebo group (1.5 ± 0.39). The NRS analysis showed that there was a statistically significant difference in pain intensity between the treatment and placebo groups ( p < 0.001) at every timepoint. Additionally, the sum of pain intensity difference at 6 h (SPID6) of the treatment group (34.32 ± 1.41) showed a significant difference ( p < 0.0001) and was 20.19 times better when compared to placebo (1.7 ± 0.56). Based on the study results, the turmeric-boswellia-sesame formulation exhibited remarkable menstrual pain relief as compared to the placebo.

Agency British Columbia, C., et al. (2024). STRatIfication of Vulvar Squamous Cell Carcinoma by HPV and p53 Status to Guide Excision.
	No Results Available Procedure: Re-excision Local Vulvar Disease Recurrence - Local vulvar disease recurrence rate (within 3 years) in HPV-I and HPV-A vulvar squamous cell carcinoma|Health Economic Impact of implementation of HPV and p53 stratified treatment algorithms - Measure the delta in surgical parameters (surgical take backs, longer hospital stay for more extensive surgery)|Patient Reported Outcome EORTC QLQ-C30 - Measures subject's physical, psychological and social functions.|Patient Reported Outcome EORTC QLQ-VU34 vulva-specific module - Measures symptoms or problems related to the genital area|Patient Decisional Conflict Scale - Change in level of patient decisional conflict is defined as the change in the Decisional Conflict Scale or subscale prior to and after treatment|Disease-specific survival is defined as the time from study enrolment to the time of death from vulvar cancer. Overall survival is defined as the time from study enrolment to the time of death from any cause.|Proportion of patients who had p16 IHC and in HPV-I VSCC who had p53 IHC performed on resection margin in an acceptable turnaround time ie >85% of patients tumours had this performed and reported within 21 days of surgery Female Not Applicable 249 Other Allocation: Randomized|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment STRIVE December 2025

Agenus, I. (2021). "A Phase 2 Study of Balstilimab Independently or in Combination With Zalifrelimab in Cervical Cancer." ClinicalTrials.gov.
	This is a randomized, non‐comparative, two‐arm Phase 2 clinical trial to assess the efficacy ,safety and pharmacokinetics of Balstilimab (Treatment Arm 1 ‐ monotherapy) or in combination with Zalifrelimab (Treatment Arm 2‐ combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first‐line platinum‐based chemotherapy.

Aghababaei, Z., et al. (2021). "Efficacy of Sesame (Sesamum indicum L.) in the Management of Incomplete Abortion: an Open-Label Randomized Controlled Clinical Trial." Complementary Medicine Research 28(6): 501‐507.
	BACKGROUND: Incomplete abortion is a common complication of pregnancy. Sesamum indicum L. is a widely used emmenagogue herb. OBJECTIVES: We designed a clinical trial to evaluate the efficacy of sesame for the removal of retained products of conception (RPOC). METHODS: In this randomized, open‐label, and controlled trial, 45 patients received sesame powder as an intervention group and 45 patients received expectant management as a control group for 5 days. The primary outcome measure was complete resolution of RPOC assessed by sonography. Secondary outcome measures were severity of patients' vaginal bleeding and pain. RESULTS: 84.1% had complete resolution of RPOC in the sesame group, while 26.2% had complete resolution of RPOC in the control group, which was statistically significant (p < 0.001). Moreover, patients in the sesame group showed a significantly more decreasing trend in pain and vaginal bleeding compared to the control group (p < 0.001). CONCLUSION: Sesame had a significant effect on the removal of RPOC and the reduction of pain and vaginal bleeding.

Aghajanian, C., et al. (2021). "Progression-free survival by investigator versus blinded independent central review in newly diagnosed patients with high-grade serous ovarian cancer: Analysis of the VELIA/GOG-3005 trial." Gynecologic Oncology 162(2): 375-381.
	OBJECTIVE: In the phase 3 VELIA/GOG-3005 trial, veliparib added to carboplatin-paclitaxel and continued as maintenance improved progression-free survival (PFS) compared to carboplatin-paclitaxel alone in patients with newly diagnosed ovarian carcinoma. Primary analysis of PFS was by investigator (INV) assessment, with a supplemental analysis of PFS by blinded independent central review (BICR). METHODS: Patients received veliparib or placebo with carboplatin-paclitaxel (6 cycles) and as maintenance (30 additional cycles). The primary analysis compared PFS in the veliparib-throughout arm to the carboplatin-paclitaxel only arm in the BRCA mutation (BRCAm), homologous recombination deficiency (HRD), and intention-to-treat (ITT) populations. Exploratory analyses of PFS in BRCA wildtype (BRCAwt), homologous recombination proficient (HRP), and HRD + BRCAwt populations were also performed. PFS per BICR and overall concordance rates between INV and BICR assessments were analyzed. RESULTS: Hazard ratios for PFS by INV and BICR were consistent in each of the primary analysis and exploratory populations. In the ITT population, median PFS per INV was 23.5 months in the veliparib-throughout arm versus 17.3 months in the control arm (hazard ratio [HR] 0.683, 95% confidence interval [CI] 0.562-0.831; P < 0.001). Median PFS by BICR was 29.3 months versus 19.2 months (HR 0.687, 95% CI 0.504-0.806). In the ITT population, the overall concordance rates between INV and BICR were 78% and 75% for the veliparib-throughout and control arms, respectively. CONCLUSIONS: Hazard ratios for PFS per BICR and per INV were consistent, with no suggestion of investigator bias. These findings support the reliability of PFS by INV in ovarian cancer trials.

Aghajanian, C., et al. (2022). "Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial." Gynecologic Oncology 164(2): 278-287.
	Objective: In the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status.; Methods: Women with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status.; Results: 1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n = 211) and gBRCAwt (n = 902) subgroups.; Conclusions: DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.; Competing Interests: Declaration of competing interest None. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aghajanova, L., et al. (2021). "Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience." Journal of Assisted Reproduction and Genetics 38(11): 2955-2963.
	PURPOSE: Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. MATERIALS AND METHODS: Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. RESULTS: There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, - 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). CONCLUSIONS: PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

Aghajanpour, S., et al. (2021). "Endometrial scratching affects gene expression of NLRP3 in patients with unexplained repeated implantation failure: a randomized control trial." International Journal of Reproductive Biomedicine 19(5 SUPPL 1): 68.
	Background: Alternative strategies have been used to augment success rate of implantation in IVF/ICSI cycles in unexplained repeated implantation failure patients. Endometrial scratching is one of these procedures. It seems scratching can affect NLRP3 gene expression which has an important role on receptivity of endometrium. NLRP3 is an intracellular sensor that detects a broad range of harmful sterile or infectious stimuli, resulting in the formation and activation of the NLRP3 inflammasome Objective: In the present study, we investigated whether gene expression of NLRP3 (NOD‐, LRR‐ and pyrin domain‐containing protein 3) is affected by endometrial injury during proliferative phase of menstrual cycle before embryo transfer. Materials and Methods: Twenty women with unexplained repeated implantation failure who failed to conceive during three or more IVF/ICSI cycles and embryo transfer were selected. The patients randomly classified into two study groups (N = 10 in each group). In the intervention group (not in the control group), endometrial scratching was done on day 9‐13 in the proliferative phase of the preceding menstrual cycle. Then, endometrial biopsies of the intervention and control groups were performed in the luteal phase (on 19‐21 day). The RNA of all samples was extracted and cDNA synthesis was performed. The expression of NLRP3 was quantified by quantitative real‐time PCR. Results:NLRP3 gene expression from all samples was investigated. Relative expression of NLRP3 was lower in the intervention samples compared to the controls. Conclusion: The inflammasome components are suggested as a novel family of endometrial biomarkers. This result is in consistent with other studies that showed dysregulated inflammasome activation has involved in the disruption of maternal‐fetal immune‐tolerance and in pregnancy complications.

Aghajanpour, S., et al. (2022). "Endometrial scratching: A strategy to stimulate the angiogenesis aspect of implantation in unexplained, repeated implantation failure." Human Reproduction 37(Supplement 1): i370.
	Study question: Does endometrial scratching serve as an angiogenic stimulator during implantation in unexplained, repeated implantation failure (uRIF) patients? Summary answer: Endometrial scratching can reimburse and regulate genes involved in both endometrial angiogenesis and receptivity. What is known already: The vascular endothelial growth factor (VEGF), as an angiogenic factor, is well-known for its function in a variety of physiological and pathological aspects of female reproduction. Following the embryo transfer in the In-Vitro Fertilization cycles, the most challenging clinical obstacle to overcome is RIF. Endometrial scratching is a technique considered as an option for enhancing the embryo implantation of uRIF patients by modulating the different cellular and molecular components regulating endometrial receptivity before and during implantation. Study design, size, duration: Twenty uRIF patients were enrolled based on a randomized controlled trial (RCT) to study the expression of genes involved in endometrial angiogenesis and receptivity functions (VEGFR1, VEGFR2, COL18A1, E-cadherin, FGF1) following ES. Ten uRIF patients were randomly assigned to the intervention group (twice endometrial sampling in the follicular and luteal phases) and ten in the control group (only luteal phase sampling) prior to the ovarian stimulation cycle. Participants/materials, setting, methods: Women who failed to conceive following three or more IVF/ICSI cycles, high-quality embryo transfer, and at least one blastocyst embryo transfer cycle met the inclusion criteria. Post-biopsy endometrial samples were divided evenly. One component was placed in 10% formalin for histology dating and another in RNALater for genomic analysis and preserved at -80 degreeC for RNA extraction. Main results and the role of chance: The expression levels of VEGFR1 and VEGFR2 (both as the receptors of VEGF) were significantly increased after ES (P<0.05). The mRNA expression level of COL18A1 was significantly decreased after ES. COL18A1 is an inhibitor of VEGF which can impede VEGF-mediated signaling and endothelial cell proliferation, via blocking of its receptor specifically VEGFR2. The E-cadherin expression level was significantly decreased (P<0.05) in the endometrium of the intervention group after scratching. E-cadherin is a cell-cell adhesion molecule that has a pivotal role in maintaining normal epithelial architecture, establishing cell polarity, glandular differentiation, and morphogenesis. Data showed that Fibroblast Growth Factor1 (FGF1) expression level was significantly increased in the intervention group (P<0.05). FGF1 promotes the formation of blood vessels which improves endometrial trophoblastic interaction and affects embryo implantation. Limitations, reasons for caution: To further understand the function of these changes, it is preferable to compare the data with endometrium from a fertile group, which is ongoing. Wider implications of the findings: On the timeline of embryo implantation, angiogenic factors (e.g., VEGFR1 and VEGFR2), their inhibitors (e.g., E-cadherin and COL18A1), and activators (e.g., FGF1) work together to establish a dynamic environment responsible for endometrial receptivity, which has been compromised in the endometrium of RIF patients.ES can reimburse and regulate these angiogenesis processes.

Aghbash, P. S., et al. (2022). "Monoclonal antibodies in cervical malignancy-related HPV." Frontiers in Oncology 12: 904790.
	Despite many efforts to treat HPV infection, cervical cancer survival is still poor for several reasons, including resistance to chemotherapy and relapse. Numerous treatments such as surgery, radiation therapy, immune cell-based therapies, siRNA combined with various drugs, and immunotherapy are being studied and performed to provide the best treatment. Depending on the stage and size of the tumor, methods such as radical hysterectomy, pelvic lymphadenectomy, or chemotherapy can be utilized to treat cervical cancer. While accepted, these treatments lead to interruptions in cellular pathways and immune system homeostasis. In addition to a low survival rate, cervical neoplasm incidence has been rising significantly. However, new strategies have been proposed to increase patient survival while reducing the toxicity of chemotherapy, including targeted therapy and monoclonal antibodies. In this article, we discuss the types and potential therapeutic roles of monoclonal antibodies in cervical cancer.Copyright © 2022 Aghbash, Hemmat, Fathi and Baghi.

Agholme, F., et al. (2023). "POWER: an open, single-arm, post-market clinical trial using the TENA SmartCare Change Indicator in a home environment." Archives of Medical Science 19(1): 270-273.
	Introduction: This clinical trial tested the use of the TENA SmartCare Change Indicator in a homecare environment. Method(s): The trial included 35 elderly subjects with urinary incontinence. The trial lasted for 3 weeks. The primary outcome was the reduction in manual absorbing product checks between the baseline (first) and the investigational (third) week. Result(s): The numbers of checks and leakages were significantly reduced by 16% (p = 0.001) and 40% (p = 0.0051). Conclusion(s): Use of the device led to a reduction in the numbers of manual checks and leakages. The device appears to be safe, well tolerated and easy to use.Copyright © 2023 Termedia & Banach.

Agnes, A., et al. (2021). "ORAL ADMINISTRATION OF SODIUM TUNGSTATE IN HEALTHY WOMEN OF CHILDBEARING AGE IS SAFE AND WELL-TOLERATED. Results OF TWO PHASE I STUDIES OF A DRUG IN DEVELOPMENT TO TREAT FEMALE INFERTILITY." Fertility and Sterility 116(3): e422.
	Objective: To assess the safety, tolerability, and pharmacokinetic profile of sodium tungstate (ST), a drug in development to treat female infertility. Materials and Methods: Two phase I, randomized, double‐blind, placebo‐controlled clinical trials were conducted, both administering ST or placebo, oral and daily, during a menstrual cycle. The doses tested were 100mg (n=7), 200mg (n=7), 300mg (n=8) and placebo (n=8) in the first study, and 500mg (n=8) vs placebo (n=2) in the second one. Safety and tolerability were evaluated by the incidence of adverse events (AEs), physical and gynecologic evaluation also with TVUS, records of vital signs and clinical laboratory results, before and during the treatment, and after a 28‐day follow‐up period. Individual blood samples were obtained at baseline,+1h, +2h,+3h,+3.33h,+3.66h, +4h, +4.33h, +4.66h, +5h, +6h, +8h, +12h, +16h, +20h, +24h, +48h, +72h, +144h, D14, D21, D28 and D28+72h. Pharmacokinetic analysis were performed using a non‐compartimental analysis approach, a PK/PD data management and modeling software package. Descriptive statistics were provided for all safety variables. The studies were authorized by the Spanish Health Agency and Ethics Committee. Results: Results showed that ST was safe and well‐tolerated at all doses, up to 500mg/day. No relevant changes were observed for gynecologic and physical evaluation, vital signs and laboratory tests. Few individual laboratory results out of the normal ranges were observed and had no clinical relevance. Few related AEs were observed and were qualified as mild or moderate. The AEs were distributed in the placebo and the treated groups with similar frequency, except for nausea (10% vs 17%). The most frequent (>5% frequency) AEs observed with ST were headache (17%), nausea (17%), somnolence (7%) and nasopharyngitis (7%). No dose relationship seemed to exist in reported AEs. ST pharmacokinetic curves were similar at all doses tested (100‐500 mg/day), with a fast peak absorption, mean Tmax between 4 and 5 hours. No accumulation was observed in any of the doses studied, since the Cmax values on day 28 were similar to those on day 1. Cmax and AUC increased with increasing dose; however, the linearity observed within the range of 100 to 300 mg/day disappeared with 500 mg/day. Conclusions: Oral treatment with ST is safe, well‐tolerated, and has a well‐characterized pharmacokinetic profile in healthy women of childbearing age at doses of up to 500mg/day. Future phase II studies are well‐supported by the available evidence. Impact Statement: These phase I studies in women of childbearing age confirm that sodium tungstate has the necessary wide safety margin and non‐complex kinetics to further investigate its therapeutic use in women's health.

Agostinis, C., et al. (2020). "Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target." Frontiers in Immunology 11: 599117.
	Endometriosis (EM) is a chronic disease characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. Ovaries and pelvic peritoneum are the most common locations for endometrial ectopic tissue, followed by deep infiltrating EM sites. The cyclic and recurrent bleeding, the progressive fibrosis and the peritoneal adhesions of ectopic endometrial glands, may cause different symptoms depending on the origin involved. EM is a frequent clinical condition affecting around 10% of women of mainly reproductive age, as well as in post-menopausal women and adolescents, especially with uterine anomalies. The risk of developing EM depends on a complex interaction between genetic, immunological, hormonal, and environmental factors. It is largely considered to arise due to a dysfunction of immunological surveillance. In fact, women with EM exhibit altered functions of peritoneal macrophages, lymphocytes and natural killer cells, as well as levels of inflammatory mediators and growth factors in the peritoneal fluid. In EM patients, peritoneal macrophages are preponderant and highly active compared to healthy women. Peritoneal macrophages are able to regulate the events that determine the production of cytokines, prostaglandins, growth factors and complement components. Several studies have shown alteration in the regulation of the complement activation, leading to chronic inflammation characteristic of EM. Aberrant regulation/activation of the complement system has been observed in the peritoneal cavity of women affected by EM. Thus, complement inhibition may represent a new approach for the treatment of EM, given that a number of complement inhibitors are under pre-clinical and clinical development. Such an intervention may provide a broader therapeutic control of complement-mediated inflammatory damage in EM patients. This review will focus on our current understanding of the role of complement activation in EM and possible modalities available for complement-based therapy.© Copyright © 2021 Agostinis, Balduit, Mangogna, Zito, Romano, Ricci, Kishore and Bulla.

Aguaviva, B., et al. (2024). "Dietary interventions in the treatment of polycystic ovary syndrome: A bibliographic review." Clinica e Investigacion en Ginecologia y Obstetricia 51(1): 100911.
	Polycystic ovary syndrome (PCOS) is a female endocrinopathy recognized as a heterogeneous disorder characterized by hyperandrogenism and ovulatory dysfunction that leads to fertility problems. In addition, patients usually present with associated symptoms such as insulin resistance, glucose intolerance, central obesity and/or metabolic syndrome that can induce an increased risk of cardiovascular disease. Since one of the main goals of PCOS is to reduce the metabolic consequences related to obesity, insulin resistance, and the metabolic syndrome, targeted dietary interventions may be effective in treating PCOS. A bibliographic search has been carried out in different databases such as Web of Science, Pubmed and Google Scholar, establishing previously defined search criteria. Eleven have been chosen for full review and critical analysis. Among the different interventions that have been used, dietary strategies have been followed such as the dietary approaches to stop hypertension (DASH), modifications in carbohydrates, the inclusion of a certain food in the usual dietary pattern and/or lifestyle modifications. Of the results obtained, we highlight the improvements in body markers with a DASH diet, the benefits promoted by diets with modifications in carbohydrates, in insulin resistance and hormonal markers and favorable effects on clinical manifestations related to hyperandrogenism, fostered by soy consumption and lifestyle modifications., El sindrome del ovario poliquistico (SOP), es una endocrinopatia femenina reconocida como un trastorno heterogeneo caracterizado por un hiperandrogenismo y una disfuncion ovulatoria que conlleva problemas de fertilidad. Ademas, las pacientes suelen presentar una sintomatologia asociada como la resistencia a la insulina, la intolerancia a la glucosa, la obesidad central y/o el sindrome metabolico que pueden inducir a un aumento del riesgo de enfermedad cardiovascular. Dado que uno de los principales objetivos del tratamiento del SOP es reducir las consecuencias metabolicas relacionadas con la obesidad, la resistencia a la insulina y el sindrome metabolico, las intervenciones dieteticas dirigidas a este proposito pueden resultar eficaces en el tratamiento de este padecimiento. Se ha llevado a cabo una busqueda bibliografica en diferentes bases de datos como Web of Science (WOS), PubMed y Google Academico estableciendo unos criterios de busqueda previamente definidos. Se han elegido 11 trabajos para su revision completa y analisis critico. Entre las diferentes intervenciones que se han utilizado, se han seguido estrategias dieteticas como la Dietary Approaches to Stop Hypertension (DASH), modificaciones en los hidratos de carbono (HC), la inclusion de algun alimento determinado en el patron dietetico habitual y/o los cambios en el estilo de vida. De los resultados obtenidos, destacan las mejoras propiciadas en los marcadores corporales con un regimen DASH, los beneficios promovidos por dietas con modificaciones en los HC, en la resistencia insulinica (IR) y los marcadores hormonales, asi como los efectos favorables en las manifestaciones clinicas relacionadas con el hiperandrogenismo, fomentados por el consumo de soja y las modificaciones en el estilo de vida (LSM).Copyright © 2023 The Authors

Agur, W., et al. (2021). "Treating Women with Recurrent Stress Urinary Incontinence: a Hornet's Nest Still Needing Proper Clinical Evidence." European Urology 79(1): 6‐7.
	Evidence is lacking on the best treatment for women presenting with recurrent stress urinary incontinence. PURSUIT is a randomised trial of urethral bulking agent injection versus surgical intervention. It will provide high‐quality evidence to aid counselling and inform choice. https://research-information.bris.ac.uk/ws/portalfiles/portal/256087477/PURSUIT_Editorial_280920_COI.pdf

Ahangari, F., et al. (2023). "The Efficacy of Salvia officinalis on the Prevention of Recurrent Vulvo-vaginal Candidiasis: A Randomized, Controlled Clinical Trial." Current Women's Health Reviews 19(4): e081222211757.
	Background: In addition to physical discomfort, recurrent vulvovaginal candidiasis impos-es a significant financial and psychosocial burden, such as lower levels of self-esteem, a higher level of stress, clinical depression, and less satisfaction with their life. Recurrent vulvovaginal candidiasis interferes with emotional and sexual relationships. Objective(s): This study aimed to compare the effect of vaginal Salvia officinalis, clotrimazole, and their combination on the prevention of recurrent vulvovaginal candidiasis. Method(s): This randomized triple-blinded trial was conducted on 111 women aged 18-49 years with vulvovaginal candidiasis. Participants were randomly assigned into one of the three groups of vaginal tablets of Salvia officinalis 400 mg and placebo of clotrimazole 100 mg, clotrimazole 100 mg and placebo of Salvia officinalis 400 mg, or Salvia officinalis and clotrimazole that were applied every night for 7 consecutive days. A recurrence rate of vulvovaginal candidiasis was evaluated by WET test and vaginitis symptoms examination after 12 weeks. In the case of positive evaluation, the culture of vaginal discharge was performed. Result(s): Totally, 29 patients (80.6%) in group clotrimazole, 33 patients (94.3%) in group Salvia offic-inalis and 35 patients (97.2%) in group Salvia officinalis-clotrimazole were treated (P = 0.43). Out of cured patients, 4 (13.8%) patients in the group clotrimazole, 1 patient (3%) in group Salvia officinalis, and no case in group Salvia officinalis-clotrimazole experienced the recurrence of infection. There was a significant difference among the 3 groups in terms of recurrence (P = 0.023). Moreover, no adverse event during the 12 weeks after treatment was observed. Conclusion(s): Adjuvant therapy of Salvia officinalis alongside routine vaginal clotrimazole could suc-cessfully prevent recurrent vulvovaginal candidiasis after three months. Clinical Trial Registration Number: IRCT2017020227311N4.Copyright © 2023 Bentham Science Publishers.

Ahc, M. (2021). "Management of Heavy Menstrual Bleeding: levonorgestrel-Releasing Intrauterine System vs. Endometrial Ablation." OB/GYN clinical alert 38(3): 1‐3.
	"SYNOPSIS: In this multicenter, randomized, noninferiority trial among patients aged 34 years and older with heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system did not meet the noninferiority threshold when compared to endometrial ablation for mean blood loss at 24 months following intervention. Both interventions did lead to large decreases in blood loss and comparable satisfaction and quality-of-life scores." A synopsis of this paper: SOURCE: Beelen P, van den Brink MJ, Herman MC, et al. Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding. Am J Obstet Gynecol 2021;224:187.e1-187.e10.

Ahdi Derav, B., et al. (2023). "Effectiveness of Group Cognitive-Behavioral Therapy for Managing Anxiety and Depression in Women Following Hysterectomy for Uterine Cancer." Asian Pacific journal of cancer prevention : APJCP 24(12): 4237-4242.
	Objective: Hysterectomy as well as uterine cancer could be associated with a long-term risk of mental disorders. The purpose of this study is to investigate the effectiveness of group cognitive-behavioral therapy (GCBT) in reducing anxiety and depression in women who have undergone hysterectomy for uterine cancer.; Method: This experimental, pretest-post-test study was conducted in an academic hospital. 26 women with uterine cancer who underwent hysterectomy were recruited and randomly divided into two equal groups as the experimental and control groups. The experimental group was treated by GCBT for eight 1-hour sessions (by a senior psychology expert) every week until 8 weeks. Otherwise, no intervention was performed for the control group. The anxiety and depression scores of all participants were assessed and compared before and after the therapy sessions by Beck Anxiety (BAI) and Beck Depression-second version (BDI-II) questionnaires.; Results: The mean±SD age of the participants was 33.6±4.1. Our result found significant different after GCBT in both anxiety (p=0.000) and depression (p=0.000) scores in the experimental group. However, no differences between pre and post-test scores in the control group were observed. Compared to the control group the rate of depression (p=0.000) and anxiety (p=0.000) in the case group was significantly decreased after therapy.; Conclusion: GCBT is effective in reducing anxiety and depression in women after hysterectomy. The use of GCBT in oncology centers along with medical treatments to reduce mental distress, improve mental health, and accelerate the recovery process of patients with uterine cancer and other cancers seems necessary.

Ahmad, G., et al. (2020). "Barrier agents for adhesion prevention after gynaecological surgery." The Cochrane Database of Systematic Reviews 3: CD000475.
	Background: Pelvic adhesions can form secondary to inflammation, endometriosis, or surgical trauma. Strategies to reduce pelvic adhesion formation include placing barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene, and fibrin or collagen sheets between pelvic structures.; Objectives: To evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth, and postoperative adhesions in women of reproductive age.; Search Methods: We searched the following databases in August 2019: the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries. We searched reference lists of relevant papers, conference proceedings, and grey literature sources. We contacted pharmaceutical companies for information and handsearched relevant journals and conference abstracts.; Selection Criteria: Randomised controlled trials (RCTs) on the use of barrier agents compared with other barrier agents, placebo, or no treatment for prevention of adhesions in women undergoing gynaecological surgery.; Data Collection and Analysis: Three review authors independently assessed trials for eligibility and risk of bias and extracted data. We calculated odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) using a fixed-effect model. We assessed the overall quality of the evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods.; Main Results: We included 19 RCTs (1316 women). Seven RCTs randomised women; the remainder randomised pelvic organs. Laparoscopy (eight RCTs) and laparotomy (11 RCTs) were the primary surgical techniques. Indications for surgery included myomectomy (seven RCTs), ovarian surgery (five RCTs), pelvic adhesions (five RCTs), endometriosis (one RCT), and mixed gynaecological surgery (one RCT). The sole indication for surgery in three of the RCTs was infertility. Thirteen RCTs reported commercial funding; the rest did not state their source of funding. No studies reported our primary outcomes of pelvic pain and live birth rate. Oxidised regenerated cellulose versus no treatment at laparoscopy or laparotomy (13 RCTs) At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose at laparoscopy reduced the incidence of de novo adhesions (OR 0.50, 95% CI 0.30 to 0.83, 3 RCTs, 360 participants; I² = 75%; very low-quality evidence) or of re-formed adhesions (OR 0.17, 95% CI 0.07 to 0.41, 3 RCTs, 100 participants; I² = 36%; very low-quality evidence). At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose affected the incidence of de novo adhesions after laparotomy (OR 0.72, 95% CI 0.42 to 1.25, 1 RCT, 271 participants; very low-quality evidence). However, the incidence of re-formed adhesions may have been reduced in the intervention group (OR 0.38, 95% CI 0.27 to 0.55, 6 RCTs, 554 participants; I² = 41%; low-quality evidence). No studies reported results on pelvic pain, live birth rate, adhesion score, or clinical pregnancy rate. Expanded polytetrafluoroethylene versus oxidised regenerated cellulose at gynaecological surgery (two RCTs) We are uncertain whether expanded polytetrafluoroethylene reduced the incidence of de novo adhesions at second-look laparoscopy (OR 0.93, 95% CI 0.26 to 3.41, 38 participants; very low-quality evidence). We are also uncertain whether expanded polytetrafluoroethylene resulted in a lower adhesion score (out of 11) (MD -3.79, 95% CI -5.12 to -2.46, 62 participants; very low-quality evidence) or a lower risk of re-formed adhesions (OR 0.13, 95% CI 0.02 to 0.80, 23 participants; very low-quality evidence) when compared with oxidised regenerated cellulose. No studies reported results regarding pelvic pain, live birth rate, or clinical pregnancy rate. Collagen membrane with polyethylene glycol and glycerol versus no treatment at naecological surgery (one RCT) Evidence suggests that collagen membrane with polyethylene glycol and glycerol may reduce the incidence of adhesions at second-look laparoscopy (OR 0.04, 95% CI 0.00 to 0.77, 47 participants; low-quality evidence). We are uncertain whether collagen membrane with polyethylene glycol and glycerol improved clinical pregnancy rate (OR 5.69, 95% CI 1.38 to 23.48, 39 participants; very low-quality evidence). One study reported adhesion scores but reported them as median scores rather than mean scores (median score 0.8 in the treatment group vs median score 1.2 in the control group) and therefore could not be included in the meta-analysis. The reported P value was 0.230, and no evidence suggests a difference between treatment and control groups. No studies reported results regarding pelvic pain or live birth rate. In total, 15 of the 19 RCTs included in this review reported adverse events. No events directly attributed to adhesion agents were reported.; Authors' Conclusions: We found no evidence on the effects of barrier agents used during pelvic surgery on pelvic pain or live birth rate in women of reproductive age because no trial reported these outcomes. It is difficult to draw credible conclusions due to lack of evidence and the low quality of included studies. Given this caveat, low-quality evidence suggests that collagen membrane with polyethylene glycol plus glycerol may be more effective than no treatment in reducing the incidence of adhesion formation following pelvic surgery. Low-quality evidence also shows that oxidised regenerated cellulose may reduce the incidence of re-formation of adhesions when compared with no treatment at laparotomy. It is not possible to draw conclusions on the relative effectiveness of these interventions due to lack of evidence. No adverse events directly attributed to the adhesion agents were reported. The quality of the evidence ranged from very low to moderate. Common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out. (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Ahmad, G., et al. (2020). "Fluid and pharmacological agents for adhesion prevention after gynaecological surgery." The Cochrane Database of Systematic Reviews 7: CD001298.
	Background: Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by conditions that include pelvic inflammatory disease and endometriosis. Adhesions are associated with comorbidities, including pelvic pain, subfertility, and small bowel obstruction. Adhesions also increase the likelihood of further surgery, causing distress and unnecessary expenses. Strategies to prevent adhesion formation include the use of fluid (also called hydroflotation) and gel agents, which aim to prevent healing tissues from touching one another, or drugs, aimed to change an aspect of the healing process, to make adhesions less likely to form.; Objectives: To evaluate the effectiveness and safety of fluid and pharmacological agents on rates of pain, live births, and adhesion prevention in women undergoing gynaecological surgery.; Search Methods: We searched: the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and Epistemonikos to 22 August 2019. We also checked the reference lists of relevant papers and contacted experts in the field.; Selection Criteria: Randomised controlled trials investigating the use of fluid (including gel) and pharmacological agents to prevent adhesions after gynaecological surgery.; Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. We assessed the overall quality of the evidence using GRADE methods. Outcomes of interest were pelvic pain; live birth rates; incidence of, mean, and changes in adhesion scores at second look-laparoscopy (SLL); clinical pregnancy, miscarriage, and ectopic pregnancy rates; quality of life at SLL; and adverse events.; Main Results: We included 32 trials (3492 women), and excluded 11. We were unable to include data from nine studies in the statistical analyses, but the findings of these studies were broadly in keeping with the findings of the meta-analyses. Hydroflotation agents versus no hydroflotation agents (10 RCTs) We are uncertain whether hydroflotation agents affected pelvic pain (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.52 to 2.09; one study, 226 women; very low-quality evidence). It is unclear whether hydroflotation agents affected live birth rates (OR 0.67, 95% CI 0.29 to 1.58; two studies, 208 women; low-quality evidence) compared with no treatment. Hydroflotation agents reduced the incidence of adhesions at SLL when compared with no treatment (OR 0.34, 95% CI 0.22 to 0.55, four studies, 566 women; high-quality evidence). The evidence suggests that in women with an 84% chance of having adhesions at SLL with no treatment, using hydroflotation agents would result in 54% to 75% having adhesions. Hydroflotation agents probably made little or no difference to mean adhesion score at SLL (standardised mean difference (SMD) -0.06, 95% CI -0.20 to 0.09; four studies, 722 women; moderate-quality evidence). It is unclear whether hydroflotation agents affected clinical pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14; three studies, 310 women; moderate-quality evidence) compared with no treatment. This suggests that in women with a 26% chance of clinical pregnancy with no treatment, using hydroflotation agents would result in a clinical pregnancy rate of 11% to 28%. No studies reported any adverse events attributable to the intervention. Gel agents versus no treatment (12 RCTs) No studies in this comparison reported pelvic pain or live birth rate. Gel agents reduced the incidence of adhesions at SLL compared with no treatment (OR 0.26, 95% CI 0.12 to 0.57; five studies, 147 women; high-quality evidence). This suggests that in women with an 84% chance of having adhesions at SLL with no treatment, the use of gel agents would result in 39% to 75% having adhesions. It is unclear whether gel agents affected mean adhesion scores at SLL (SMD -0.50, 95% CI -1.09 to 0.09; four studies, 159 women; moderate-quality evidence), or clinical pregnancy rate (OR 0.20, 95% CI 0.02 to 2.02; one study, 30 women; low-quality evidence). No studies in this comparison re orted on adverse events attributable to the intervention. Gel agents versus hydroflotation agents when used as an instillant (3 RCTs) No studies in this comparison reported pelvic pain, live birth rate or clinical pregnancy rate. Gel agents probably reduce the incidence of adhesions at SLL when compared with hydroflotation agents (OR 0.50, 95% CI 0.31 to 0.83; three studies, 538 women; moderate-quality evidence). This suggests that in women with a 46% chance of having adhesions at SLL with a hydroflotation agent, the use of gel agents would result in 21% to 41% having adhesions. We are uncertain whether gel agents improved mean adhesion scores at SLL when compared with hydroflotation agents (MD -0.79, 95% CI -0.82 to -0.76; one study, 77 women; very low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Steroids (any route) versus no steroids (4 RCTs) No studies in this comparison reported pelvic pain, incidence of adhesions at SLL or mean adhesion score at SLL. It is unclear whether steroids affected live birth rates compared with no steroids (OR 0.65, 95% CI 0.26 to 1.62; two studies, 223 women; low-quality evidence), or clinical pregnancy rates (OR 1.01, 95% CI 0.66 to 1.55; three studies, 410 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention.; Authors' Conclusions: Gels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but we found no evidence indicating that they improve fertility outcomes or pelvic pain, and further research is required in this area. It is also worth noting that for some comparisons, wide confidence intervals crossing the line of no effect meant that clinical harm as a result of interventions could not be excluded. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society score. Statistical findings should be reported in full. No studies reported any adverse events attributable to intervention. (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Ahmad, M. F. (2020). "Ganoderma lucidum: A rational pharmacological approach to surmount cancer." Journal of Ethnopharmacology 260: 113047.
	Ethnopharmacological relevance: Ganoderma lucidum (G. lucidum) has been broadly used for health endorsement as well as longevity for over 2000 years in Asian countries. It is an example of an ancient remedy and known as immortality mushroom. It has been employed as a health promoting agent owing to its broad pharmacological and therapeutical approaches. It has been confirmed that G. lucidum exhibits significant potency to prevent and treat different types of cancers such as breast, prostate, colon, lung and cervical. Aim of the study: To explore anticancer effects of various pharmacologically active compounds obtained from G. lucidum and their possible mechanism of action. Material(s) and Method(s): A literature search was conducted using PubMed, Goggle Scholar, Saudi Digital Library and Cochrane Library until October 11, 2019. Search was made by using keywords such as anticancer evidence, mechanism of action, pharmacology, antioxidant, toxicity, chemotherapy, triterpenoids and polysaccharides of G. lucidum. Result(s): Various chemical compounds from G. lucidum exhibit anticancer properties mainly through diverse mechanism such as cytotoxic properties, host immunomodulators, metabolizing enzymes induction, prohibit the expression of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) in cancer cells. Among the various compounds of G. lucidum triterpenoids and polysaccharides are under the major consideration of studies due to their several evidence of preclinical and clinical studies against cancer. Conclusion(s): Natural alternatives associated with mild side effects are the basic human need of present therapy to eradicate the new emerging disorders. This review is an attempt to compile pharmacologically active compounds of G. lucidum those exhibit anti cancer effects either alone or along with chemotherapy and anticancer mechanisms against various cancer cells, clinical trials, chemotherapy induced toxicity challenges with limitations. It acts as a possible substitute to combat cancer growth with advance and conventional combination therapies as natural alternatives.Copyright © 2020 Elsevier B.V.

Ahmadian, S., et al. (2020). "Effectiveness of Stem Cell Therapy in the Treatment of Ovarian Disorders and Female Infertility: A Systematic Review." Current stem cell research & therapy 15(2): 173-186.
	Background: Infertility is a major problem worldwide. Various strategies are being used to develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current developments.; Objective: Different published studies on stem cell-based therapy for the treatment of various types of ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female population in animal or human clinical studies are systematically reviewed.; Methods: We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest. A comprehensive online search was done using the criteria targeting the application of stem cells in animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of studies. The stem cell type, source, dosage, route of administration were highlighted in various POI animals models. Non-relevant and review articles were excluded.; Outcomes: 648 published studies were identified during the initial comprehensive search process from which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase fertility rate.; Conclusion: The evidence suggests that stem cell-based therapies could be considered as an alternative modality to deal with women undergoing POI. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ahmadian, S., et al. (2019). "Effectiveness of Stem Cell Therapy in Treatment of Ovarian Disorders and Female Infertility: A Systematic Review." Current stem cell research & therapy.
	BACKGROUND: Infertility is a major problem worldwide. Various strategies are being used to develop better treatments for infertility. On trending, the strategy is stem cell therapy. In this study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current developments. OBJECTIVE: Different published studies on stem cell-based therapy for the treatment of various types of ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female population in animal or human clinical studies systematically reviewed. METHOD: We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest. A comprehensive online search was done using including criteria targeting application of stem cells in animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of studies. The stem cell type, source, dosage, route of administration were highlighted in various POI animals models. Non-relevant and review articles were excluded. OUTCOMES: 648 published studies were identified during the initial comprehensive search process from which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase fertility rate. CONCLUSION: The evidence suggests that stem cell-based therapies could be considered as an alternative modality to deal with women undergoing POI.

Ahmed, A.-Z., et al. (2021). "A systematic review and meta-analysis of the selenium supplementation effects on cardiometabolic and hormonal parameters of PCOS patients."
	
Ahmed, M. and E.-M. Akmal (2022). "Intrauterine infusion of autologous platelet-rich plasma in women with recurrent implantation failure." PROSPERO International prospective register of systematic reviews.
	
Ahmed, M., et al. (2024). "Is high-intensity focused ultrasound a magical solution to endometriosis? A systematic review."
	
Ahmed, N., et al. (2022). "Bioactive Yoghurt Containing Curcumin and Chlorogenic Acid Reduces Inflammation in Postmenopausal Women." Nutrients 14(21).
	Menopause is marked by a gradual and permanent decrease of estrogen from the ovaries, leading to metabolic and physiological changes in the body. Combined with increased body mass index, postmenopausal women have elevated systemic inflammation and metabolic disturbances leading to increased risk of developing chronic diseases. A bioactive coconut yoghurt containing curcumin and chlorogenic acid was developed with the potential to target inflammatory processes. In this randomized crossover study, healthy postmenopausal women with a BMI of 25-40 were recruited to consume 125 g of either the bioactive or placebo yoghurt. Blood samples were collected at baseline, 30 min, and 1, 2, 3 and 4 h postprandially. Plasma inflammatory markers (TNFα and IL6) and metabolic markers (triglycerides, insulin and glucose) were measured. Participants had significantly lower plasma TNFα C max after consumption of the bioactive yoghurt compared to placebo (mean difference = 0.3 pg/mL; p = 0.04). Additionally, plasma TNFα was significantly lower postprandially compared to baseline after consumption of the bioactive yogurt but not the placebo. No differences were observed in the metabolic markers measured. Conclusions: The bioactive yoghurt fortified with curcumin and chlorogenic acid has the potential to reduce inflammatory mediators; however, a larger and longer-term study is required to confirm these findings.

Ahmed, R. J., et al. (2021). "The cost implications of continuous glucose monitoring in pregnant women with type 1 diabetes in 3 Canadian provinces: a posthoc cost analysis of the CONCEPTT trial." CMAJ open 9(2): E627‐E634.
	BACKGROUND: The Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT) found improved health outcomes for mothers and their infants among those randomized to self‐monitoring of blood glucose (SMBG) with continuous glucose monitoring (CGM) compared with SMBG alone. In this study, we evaluated whether CGM or standard SMBG was more or less costly from the perspective of a third‐party payer. METHODS: We conducted a posthoc analysis of data from the CONCEPTT trial (Mar. 25, 2013, to Mar. 22, 2016). Health care resource data from 215 pregnant women, randomized to CGM or SMBG, were collected from 31 hospitals in 7 countries. We determined resource costs posthoc based on prices from hospitals in 3 Canadian provinces (Ontario, British Columbia, Alberta). The primary outcome was the difference between groups in the mean total cost of care for mother and infant dyads, paid by each government (i.e., the third‐party payer) from randomization to hospital discharge (time horizon). The secondary outcome included CGM and SMBG costs not paid by governments (e.g., glucose monitoring devices and supplies). RESULTS: The mean total cost of care was lower in the CGM group compared with the SMBG group in each province (Ontario: $13 270.25 v. $18 465.21, difference in mean total cost [DMT] ‐$5194.96, 95% confidence interval [CI] ‐$9841 to ‐$1395; BC: $13 480.57 v. $18 762.17, DMT ‐$5281.60, 95% CI ‐$9964 to ‐$1382; Alberta: $13 294.39 v. $18 674.45, DMT ‐$5380.06, 95% CI ‐$10 216 to ‐$1490). There was no difference in the secondary outcome. INTERPRETATION: Government health care costs are lower when CGM is paid by the patient, driven by lower costs from reduced use of the neonatal intensive care unit in the CGM group; however, when governments pay for CGM equipment, there is no overall cost difference between CGM and SMBG. Governments should consider paying for CGM, as it results in improved maternal and neonatal outcomes with no added overall cost. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01788527.

Ahmed, s., et al. (2022). "trans-vaginal hydro-laparoscope and hysterosalpingography in the infertility assessment."
	
Ahmed, S., et al. (2022). "Efficacy of Intrauterine Infusion of Autologous Platelet-Rich Plasma for Women with Repeated Embryo Implantation Failure: A Systematic Review and Meta‐Analysis of Randomized controlled trials." PROSPERO International prospective register of systematic reviews.
	
Ahmed, S. I., et al. (2022). "Prophylactic antibiotics for uterine evacuation procedures to treat miscarriage." Cochrane Database of Systematic Reviews 2022(1): CD014844.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. The objective of this review is to evaluate the effectiveness of routine antibiotic prophylaxis to women undergoing uterine evacuation procedures to treat miscarriage.Copyright © The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Ahn Eugene, R., et al. (2023). "Pertuzumab Plus Trastuzumab in Patients With Endometrial Cancer With ERBB2/3 Amplification, Overexpression, or Mutation: Results From the TAPUR Study." JCO precision oncology 7: e2200609.
	Purpose: The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with ERBB2 or ERBB3 (ERBB2/3) amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported.; Methods: Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2/3 amplification, overexpression, or mutation. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+) duration. Secondary end points include safety, duration of response, duration of SD, progression-free survival (PFS), and overall survival (OS).; Results: Twenty-eight patients were enrolled from March 2017 to November 2019; all patients were evaluable for efficacy and toxicity. Seventeen patients had tumors with ERBB2/3 amplification and/or overexpression, eight with both ERBB2 amplification and ERBB2/3 mutations, and three with only ERBB2 mutations. Ten patients had DC (two partial response and eight SD16+); all 10 had ERBB2 amplification, and 6 of the 10 patients with DC had >1 ERBB2/3 alteration. DC and OR rates were 37% (95% CI, 21 to 50) and 7% (95% CI, 1 to 24), respectively; the median PFS and median OS were 16 weeks (95% CI, 10-28) and 61 weeks (95% CI, 24-105), respectively. One patient experienced a grade 3 serious adverse event (muscle weakness) at least possibly related to P + T.; Conclusion: P + T has antitumor activity in heavily pretreated patients with EC with ERBB2 amplification and warrants additional study.

Ahnert, J. R., et al. (2023). "Phase 2, multicenter open-label basket trial of nab-sirolimus for patients with inactivating alterations in TSC1 or TSC2 (PRECISION I)." Cancer Research 83(8 Supplement).
	nab-Sirolimus is a novel albumin-bound mTOR inhibitor (mTORi) approved in the US for adult patients with malignant PEComa. In an exploratory analysis of the pivotal AMPECT trial of nabsirolimus in advanced malignant PEComa (NCT02494570), 8/9 (89%) and 1/5 (20%) patients with inactivating alterations in TSC1 and TSC2, respectively, had confirmed response (Wagner, J Clin Oncol, 2021). TSC1 and TSC2 alterations have been observed in patients with a broad variety of cancers. Most treatment-related adverse events in AMPECT were grade 1/2 (none were grade >=4) and were consistent with long-term treatment of nab-sirolimus. PRECISION I (NCT05103358) will evaluate efficacy and safety of nab-sirolimus in patients with TSC1 (Arm A) and TSC2 (Arm B) alterations. Eligible patients are >=12 years old and mTORi-naive, possess malignant solid tumors with TSC1 or TSC2 inactivating alterations (confirmed by central review of sequencing reports), and have received appropriate standard treatments, as determined by the investigator. nab-Sirolimus 100 mg/m2 will be given weekly intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate per independent radiographic review (IRR) using RECIST v1.1. Other endpoints include duration of response, time to response, progressionfree survival by IRR, overall survival, patient-reported quality of life, and safety. Enrollment began March 2022. Collaboration with leading next-generation sequencing vendors will expedite the identification of patients with qualifying TSC1 or TSC2 mutations; study access will be facilitated through a "just-in-time" approach to trial location activation. Based on the prevalence of TSC1 or TSC2 inactivating alterations, the most frequent tumor types expected are bladder, hepatobiliary, endometrial, soft tissue sarcoma, ovarian, and esophagogastric (Table). .

Ahren, I. L., et al. (2023). "Decreasing the Adverse Effects in Pelvic Radiation Therapy: A Randomized Controlled Trial Evaluating the Use of Probiotics." Advances in Radiation Oncology 8(1): 101089.
	Purpose: The aim of this randomized controlled trial was to evaluate the potential benefit from 2 probiotic bacteria of the species Lactiplantibacillus plantarum against radiation therapy-induced comorbidities. Methods and Materials: Women (>18 years of age) scheduled for radiation therapy because of gynecologic cancer were randomly allocated to consume placebo or either low-dose probiotics (1 x 1010 colony-forming unit/capsule twice daily) or high-dose probiotics (5 x 1010 colony-forming unit/capsule twice daily). The intervention started approximately 1 week before the onset of radiation therapy and continued until 2 weeks after completion. During this period the participants were daily filling in a study diary documenting the incidence and severity of symptoms, intake of concomitant medication, and stool consistency. The primary endpoint was the probiotic effect on the mean number of loose stools during radiation therapy. Result(s): Of the 97 randomized women, 75 provided data for the analysis of the results. The mean number of loose stools (sum of Bristol stool type 6 and 7) was not significantly reduced in the probiotic groups, but there was a significant reduction in the mean number of days with >1 loose stool with 15.04 +/- 8.92 days in the placebo and 8.65 +/- 5.93 days in the high-dose probiotics group (P = .014). The benefit was even more pronounced in the 2 weeks following the end of radiation therapy (P = .005). Moreover, intake of the probiotics resulted in a reduced severity of the symptoms grinding abdominal pain (P = .041) and defecation urgency (P = .08) and a reduced percentage of days with these symptoms (P = .023 and P = .042, respectively), compared with placebo. There were no differences regarding reported adverse events. Conclusion(s): Intake of the 2 probiotic bacteria was beneficial and reduced many measures or symptoms of the radiation-induced toxicity in women treated for gynecologic cancer.Copyright © 2022 The Authors

Ahsen DemİRhan, K. and İ. Kevser (2023). "The effect of telemedicine interventions on patient outcomes in gynecological surgery: A systematic review and meta-analysis study."
	
Ai, F., et al. (2022). "Effect of estrogen on vaginal complications of pessary use: a systematic review and meta-analysis." Climacteric 25(6): 533-542.
	Objective: We aimed to systematically review the impact of local estrogen use in combination with a pessary on vaginal complications in postmenopausal women with pelvic organ prolapse (POP). Method(s): We searched databases including Medline, Embase, PubMed, Clinical Trials and the Cochrane Central Register of Controlled Trials for relevant literature published in English from inception to 31 May 2021. Only randomized controlled trials (RCTs) and cohort studies were included. Result(s): In total, five studies were included (three RCTs, one prospective study and one retrospective cohort study). The meta-analysis was performed with subgroups. Our results indicated a significantly lower incidence of bacterial vaginosis (BV) among postmenopausal women who used estrogen than among controls, with a total pooled odds ratio (OR) of 0.29 (95% confidence interval [CI]: 0.11-0.72; I 2 = 38%; p = 0.008). The summary ORs of the estrogen use group were 0.98 (95% CI: 0.59-1.63; I 2 = 41%; p = 0.95) for vaginal ulceration, 0.80 (95% CI: 0.42-1.54; I 2 = 29%; p = 0.50) for vaginal bleeding and 0.74 (95% CI: 0.35-1.58; I 2 = 35%; p = 0.44) for vaginal discharge. Conclusion(s): Local estrogen in combination with a pessary could decrease the BV rate among postmenopausal women with POP. However, consensus regarding the value of estrogen use for decreasing other pessary complications has not yet been reached. Additional multicenter RCTs with large sample sizes should be conducted to better understand the effect of estrogen use on reducing pessary-related complications.Copyright © 2022 International Menopause Society.

Aitbayeva, B., et al. (2023). "Effects of unilateral apical sling and laparoscopic sacrocolpopexy on the outcome in women with apical prolapse: randomised trial." Ginekologia polska.
	OBJECTIVES: The purpose of this study was to compare the use of unilateral apical sling versus laparoscopic sacrocolpopexy in the treatment of the apical form of pelvic organ prolapse in women. M: aterial and methods:A prospective, single-center randomized trial included 100 patients who were alternately assigned to treatment. Each patient had a >= III stage of apical or anterior-apical prolapse determined by the POP-Q system. 45 accepted for unilateral apical sling (UAS)and 55 accepted for laparoscopic sacrocolpopexy (LS). Data were compared by the One-way ANOVA test using IBM SPSS stats 19. RESULT(S): Mean operating time was significantly greater in the LS group versus UAS group, 194.6 vs 42.4 minutes, respectively (p < 0.05). The amount of intraoperative bleeding was significantly higher in the UAS group, compared to the LS group (p = 0.01). Within the follow-up period, 2 patients in UAS group and 3 patients in LS group (4.4% vs 5.4%, respectively; p = 0.9) had recurrent cystocoele. HRQoL and sexual outcomes did not differ significantly between the two treatment groups. CONCLUSION(S): s:Our data demonstrate the non-superiority one on each other of the two different approaches, except in terms of shorter operating time and higher intraoperative bleeding when UAS used. These findings raise questions about the need for long-term results of quality of life outcomes for women with genital prolapse, especially in resource-limited settings similar to Kazakhstan.

Akansha, et al. (2023). "Low Dose-Extended Letrozole versus Double Dose-Short Letrozole Protocol for Induction of Ovulation in Women with Polycystic Ovary Syndrome." International Journal of Pharmaceutical and Clinical Research 15(2): 915-923.
	Background and Aim: The major factor for anovulatory infertility is polycystic ovarian syndrome (PCOS). As a new therapeutic option, letrozole and other aromatase inhibitors (AIs) may compete with clomiphene citrate (CC) to induce ovulation in this population. The purpose of the current study was to compare the effectiveness of the low dose-extended or long letrozole protocol and the double dose-short letrozole strategy in ovulation induction in individuals with polycystic ovarian syndrome. Material(s) and Method(s): This study was done on the diagnosed cases of PCOS patients with subfertility in the department of obstetrics and gynecology for the period of 1 year. Letrozole 2.5 mg tablets were given daily for 10 days to the low dose-extended letrozole group or experimental group and tabs were given to the double dose-short letrozole group or control group. Starting on the second day of menstruation or the first day of withdrawal bleeding, take letrozole 5 mg once day for 5 days. On day 12 of the menstrual cycle, transvaginal sonography was used to quantify the endometrial thickness and count of developing follicles using a technique called folliculometry. On days 21 through 23, mid-luteal serum progesterone was tested to confirm ovulation. Result(s): The mean LH levels of the two groups did not significantly differ from one another. In the third cycle, patients in the extended letrozole group (54.28%) and the short letrozole group (18.75%), respectively, achieved multifollicular development, bearing statistically significant differences. In the first cycle, group II had more patients grow dominant follicles (18 mm) than group I, however in the second and third cycles, group I patients had more patients generate dominant follicles (18 mm). While there was a higher percentage of ovulating patients in the low dose prolonged letrozole group (76.5% versus 71.9%), there was no statistically significant difference. Conclusion(s): Low dose-extended letrozole protocol can be a better alternative to double dose-short letrozole protocol in respect to significant increase in the number of growing follicles with a higher trend to raise the ovulation rate and pregnancy rate though there were no significant differences in dominant follicle size, endometrial thickness, ovulation rate and pregnancy rate between two groups.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Akbari, A., et al. (2023). "Effect of intramuscular injection of human chorionic gonadotropin on endometrium preparation in frozen-thawed embryo transfer cycle: A randomized clinical trial." Caspian journal of internal medicine 14(2): 185-191.
	Background: Assisted reproductive therapy (ART) has been developed remarkably in these decades; however, the rate of unsuccessful embryo implantation especially in the frozen-thawed embryo transfer (FET) cycles remains high and is reported up to 70%. The current study was designed to compare the effect of intramuscular injection of hCG on endometrium preparation and embryo implantation, in women undergoing FET compared to the control group.; Methods: This clinical trial was done on 140 infertile women that underwent FET. The study sample was randomly allocated to the intervention group (two 5000 unit ampoules of hCG were injected intramuscularly before the first dose of progesterone administration) and the control group (without hCG injection). In both groups, 4 days after progesterone administration, the cleavage stage embryos were transferred. The study outcomes were biochemical pregnancy, clinical pregnancy and abortion rate.; Results: The average age of intervention and control group was 32.65±6.05 and 33.11±5.36 years, respectively. The basic information between two study groups did not differ significantly. The chemical (30% vs. 17.1%, P=0.073, relative risk (RR)=0.57) and clinical (28.6% vs. 14.3%, P=0.039, RR=0.50) pregnancy rates were higher in the intervention group compared to the control group; these higher ratios were only significant in clinical pregnancy rate. Abortion rate was not significantly (P=0.620) different between the intervention and control groups (4.3% vs. 1.4%, respectively).; Conclusion: This study showed that intramuscular injection of 10000 IU hCG before the endometrial secretory transformation phase in cleavage-stage embryo, improves IVF cycle outcomes.; Competing Interests: The authors declare no conflict of interest.

Akbaribazm, M., et al. (2021). "Female infertility and herbal medicine: An overview of the new findings." Food science & nutrition 9(10): 5869-5882.
	Infertility is defined as the failure to achieve a successful pregnancy after 12 months' sexual activity that affects 15%-17% of couples in the world and about 50% of them are related to female infertility factors. In this study, using the PRISMA checklist and MeSH keywords, 128 articles were extracted from various databases (PubMed, Cochrane library, WHO, Iranmedex, Science Direct, SID, and Google Scholar search engine) without language and time restrictions, and 128 articles were selected after eliminating duplicate studies. In this review, we present some solid evidence for role of herbal medicine in the treatment of female infertility. The results of this study showed that different parts of some plants are rich in polyphenolic compounds (isoflavones and flavonoids) and other compounds which are beneficial to in reproductive health in women. The compounds in these plants, along with regulating the female endocrine pathways, and improving symptoms of menopause, treat female reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian failure (POF), endometriosis, hyperprolactinemia, and hypothalamic dysfunction; moreover, because of their anticancer, antioxidant, and antidepressant properties, they can be used in traditional medicine or in the pharmaceutical industry as safe compounds in women's health.

Akbari-Sene, A., et al. (2023). "Intravenous Versus Intraperitoneal Dexamethasone Effects on Postoperative Nausea, Vomiting, and Pain After Laparoscopic Gynecologic Surgery: A Randomized Controlled Trial." Journal of Gynecologic Surgery 39(5): 213-219.
	Objective: This study compared the effects of intraperitoneal (i.p.) versus intravenous (i.v.) dexamethasone injection on reducing postoperative nausea and vomiting (PONV) as well as pain after gynecologic laparoscopic surgery. Material(s) and Method(s): In this randomized, triple-blinded clinical trial, 90 women who underwent laparoscopic surgery for gynecologic indications were divided randomly into 3 groups: (1) Group IV-D, single 8-mg dose of i.v. dexamethasone intraoperatively with i.p. placebo; (2) IP-D, single 8-mg dose of i.p. dexamethasone with i.v. placebo; and (3) placebo, i.v. and i.p. distilled water. PONV and pain intensity were measured every 6 hours postoperatively in the first 24 hours with a visual analogue scale (VAS). Result(s): Ninety patients were in the 3 groups, with 30 patients in each group. The mean - standard deviation age of participants was 29.38 - 4.66 years. There was a significant difference in VAS pain at 6, 12, 18, and 24 hours after surgery between groups IV-D and IP-D (p < 0.001), groups IP-D and placebo (p < 0.001), and groups IV-D and placebo (p < 0.001). PONV VAS at 6, 12, 18 and 24 hours were significantly different between groups IV-D and IP-D (p < 0.001), groups IP-D and placebo (p < 0.001), and groups IV-D and placebo (p < 0.001). Conclusion(s): Dexamethasone significantly reduced incidence and severity of PONV and pain in patients after laparoscopic gynecologic surgery, more so when using i.p. injection. Dexamethasone reduced the need for opioid analgesics.Copyright © Mary Ann Liebert, Inc.

Akdemir, A., et al. (2023). "Comparison of laparoscopic enclosed electromechanical morcellation and vaginal enclosed scalpel morcellation at laparoscopic myomectomy: A prospective randomized trial." The Journal of Obstetrics and Gynaecology Research 49(2): 691-700.
	Aim: This study aimed to compare the laparoscopic-enclosed electromechanical morcellation (LEM) with vaginal-enclosed scalpel morcellation (VSM) in laparoscopic myomectomy procedures.; Methods: One hundred eighteen patients who underwent laparoscopic myomectomy were enrolled the prospective randomized interventional clinical study in tertiary university hospital. After myomectomy, tissue removal was accomplished via either LEM using the in-glove morcellation technique or VSM.; Results: The median tissue removal time was longer in the LEM group (25 min [range: 14-55]) than the VSM group (20 min [range: 6-38] [p = 0.001]). Rescue analgesia requirement was significantly higher in the LEM group than the VSM group (mean rank: 56.92 vs. 40.92 doses, respectively; p < 0.001). There was no significant difference between preoperative and postoperative third month total scores of female sexual function index (FSFI) and subdomains in the LEM group. Conversely, all subdomains and total scores of FSFI (26.5 [16.7-34.8] vs. 22.7 [15.2-28.7]) except pain significantly worsened 3 months after operation in the VSM group.; Conclusions: LEM was associated with a longer tissue removal time and increased postoperative analgesic requirement. On the other hand, VSM was associated with worsened postoperative sexual function from baseline. (© 2022 Japan Society of Obstetrics and Gynecology.)

Aker Menekşe, N. and F. Özdemir (2023). "The effect of the approach based on the Neuman Systems Model on stress and coping in women receiving intrauterine insemination treatment: A randomized controlled trial." Health Care for Women International 44(4): 457-472.
	This randomized controlled study was conducted to determine the effect of the approach based on the Neuman Systems Model (NSM) on stress and coping in women receiving intrauterine insemination (IUI) treatment. The study participants consisted of 62 women. Data was collected using a personal information form, the COMPI Fertility Problem Stress Scale, and the COMPI Coping Strategy Scale. Women in the intervention group had lower stress levels in their personal and marital domain post-test median scores than those in the control group. Women in the intervention group also had lower active-avoidance coping method and higher meaning-based coping method post-test mean scores. The NSM-based approach is beneficial in decreasing stress and positively affects women to cope with stress. Both infertility and its treatments are stressful. Health care professionals have important responsibilities for reducing the stress of infertile women and strengthening infertile women's ability to cope. The NSM-based approach is considered to have positive effects on stress and the ability of women to cope who receive IUI treatments. In addition, IUI is a widely applied method which is used before switching to assisted reproductive techniques. If this treatment fails, the stress coping techniques learned during this treatment can be used in later treatment processes. We conducted this study to investigate the effects of the NSM-based approach on stress and coping strategies in women receiving IUI treatment.

Akhatova, A., et al. (2023). "Reproductive and Obstetric Outcomes after UAE, HIFU, and TFA of Uterine Fibroids: Systematic Review and Meta-Analysis." International Journal of Environmental Research and Public Health 20(5).
	Novel treatment options for uterine fibroids, such as uterine artery embolization (UAE), ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USgHIFU and MRgHIFU), and transcervical radiofrequency ablation (TFA) methods, are widely used in clinical practice. This systematic review and meta-analysis (CRD42022297312) aims to assess and compare reproductive and obstetric outcomes in women who underwent these minimally invasive approaches for uterine fibroids. The search was performed in PubMed, Google Scholar, ScienceDirect, Cochrane Library, Scopus, Web of Science and Embase. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and Cochrane guidelines. The articles were selected to meet the following eligibility criteria: (1) research article, (2) human subject research, and (3) the study of pregnancy outcomes after the treatment of uterine fibroids by either one of three methods-UAE, HIFU, and TFA. The analysis of 25 eligible original articles shows a similar rate of live births for UAE, USgHIFU, MRgHIFU, and TFA (70.8%, 73.5%, 70%, and 75%, respectively). The number of pregnancies varied considerably among these studies, as well as the mean age of pregnant women. However, the results of pregnancy outcomes for TFA are insufficient to draw firm conclusions, since only 24 women became pregnant in these studies, resulting in three live births. The miscarriage rate was highest in the UAE group (19.2%). USgHIFU was associated with a higher rate of placental abnormalities compared to UAE (2.8% vs. 1.6%). The pooled estimate of pregnancies was 17.31% to 44.52% after UAE, 18.69% to 78.53% after HIFU, and 2.09% to 7.63% after TFA. The available evidence confirmed that these minimally invasive uterine-sparing treatment options for uterine fibroids are a good approach for patients wishing to preserve their fertility, with comparable reproductive and obstetric outcomes among the different techniques.

Akhtar, M. A., et al. (2019). "Thyroxine replacement for subfertile women with euthyroid autoimmune thyroid disease or subclinical hypothyroidism." The Cochrane Database of Systematic Reviews 6: CD011009.
	Background: Thyroid disease is the second most common endocrine disorder affecting women of reproductive age. Subclinical hypothyroidism is diagnosed by an elevated thyroid-stimulating hormone concentration with a normal concentration of free thyroxine hormone. Autoimmune thyroid disease (ATD) is diagnosed by the presence of thyroid autoantibodies, regardless of thyroid hormone levels. Thyroxine may be a useful treatment for subfertile women with these two specific types of thyroid disease for improving pregnancy outcomes during assisted reproduction.; Objectives: To evaluate the efficacy and harms of levothyroxine replacement in subfertile women with subclinical hypothyroidism or with normal thyroid function and thyroid autoimmunity (euthyroid autoimmune thyroid disease, or euthyroid ATD) undergoing assisted reproduction.; Search Methods: We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers together with reference checking and contact with study authors and experts in the field to identify studies. We searched for all published and unpublished randomised controlled trials (RCTs) comparing thyroxine with no treatment or placebo, without language restrictions, from inception to 8 April 2019, and in consultation with the Cochrane CGF Information Specialist.; Selection Criteria: We included women undergoing assisted reproduction treatment, meaning both in vitro fertilisation and intracytoplasmic sperm injection, with a history of subfertility and with subclinical hypothyroidism or with euthyroid ATD. We excluded women with a previously known clinical hypothyroidism or already taking thyroxine or tri-iodothyronine. RCTs compared thyroxine (levothyroxine) with either placebo or no treatment.; Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our primary review outcomes were live birth and adverse events of thyroxine; our secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage.; Main Results: The review included four studies with 820 women. The included studies were of overall low risk of bias. Using GRADE methodology, we assessed the quality of evidence for the primary outcomes of this review to be very low- to low-quality evidence. Evidence was downgraded for imprecision as it was based on single, small trials with wide confidence intervals (CI). We were able to include data from three of the four included studies.In one study of women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies (autoimmune disease), the evidence suggested that thyroxine replacement may have improved live birth rate (RR 2.13, 95% CI 1.07 to 4.21; 1 RCT, n = 64; low-quality evidence) and it may have led to similar miscarriage rates (RR 0.11, 95% CI 0.01 to 1.98; 1 RCT, n = 64; low-quality evidence). The evidence suggested that women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies would have a 25% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 27% and 100%.In women with normal thyroid function and thyroid autoimmunity (euthyroid ATD), treatment with thyroxine replacement compared with placebo or no treatment may have led to similar live birth rates (risk ratio (RR) 1.04, 95% CI 0.83 to 1.29; 2 RCTs, number of participants (n) = 686; I 2 = 46%; low-quality evidence) and miscarriage rates (RR 0.83, 95% CI 0.47 to 1.46, 2 RCTs, n = 686, I 2 = 0%; low-quality evidence). The evidence suggested that women with normal thyroid function and thyroid autoimmunity would have a 31% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 26% and 40%.Adverse events were rarely reported. One RCT reported 0/32 in the thyroxine replacement group and 1/32 preterm births in the control group in women diagnosed with subclinical hypothyroidism and positive or negative anti TPO antibodies. One RCT reported 21/300 preterm births in the thyroxine replacement group and 19/300 preterm births in the control group in women diagnosed with positive anti-TPO antibodies. None of the RCTs reported on other maternal pregnancy complications, foetal complications or adverse effects of thyroxine.; Authors' Conclusions: We could draw no clear conclusions in this systematic review due to the very low to low quality of the evidence reported.

Akmansu, M., et al. (2023). "Probiotic-prebiotic usage effects on acute inflammation parameters receiving pelvic radiotherapy patients : A prospective multicentric study." Clinical Nutrition ESPEN 58: 446.
	Rationale: Patients using prebiotics or probiotics+probiotics while receiving pelvic radiotherapy were compared with the control group, and their side effects and acute inflammatory responses were examined. Method(s): The study started after the approval of the ethics committee.76 consecutive patients from 2 centers participated in the study.The patients were divided into 3 groups.The first group used a conventional diet,the second group used a conventional diet+prebiotic, and the third group used a conventional diet+a prebiotic and probiotic-containing product.16 of them were in the control group,22 of them were in the prebiotic group and 38 of them were in the probiotic+prebiotic group.Their side effects were calculated with EORTC-QLQ-CR-29 and Bristol stool scale.Inflammatory response assessment was done with TNF-alpha and IL-6. All patients underwent both a blood examination and the aforementioned tests at 1st week and at the 5th week of radiotherapy. Result(s): In patients in the control group who underwent pelvic RT without probiotic-prebiotic use such as TNF-alpha and IL-6 at 5th week, there was increase trend in acute phase reactant mean values. There was a significant increase in IL-6 in the prebiotic group,but not in TNF-alpha.There was no significant increase in TNF-alpha or IL-6 in the prebiotic+probiotic group. In prebiotic+probiotic group,there was no increase in GIS side effect parameters in EORTC-QLQ-CR-29 and bristol stool scores. Conclusion(s): This is the first prospective clinical study to evaluate the acute inflammatory effects of radiotherapy with acute phase reactants comparing it with the probiotic+prebiotic or prebiotic-only group and the control group.Absence of an increase in TNF-alpha and IL-6 in the group using prebiotic+probiotic while applying pelvic radiotherapy indicates the effectiveness of prebiotic+probiotic usage against GIS side effects Disclosure of Interest: None declaredCopyright © 2023

Aktaş, H. Ş., et al. (2022). "The effects of high intensity-interval training on vaspin, adiponectin and leptin levels in women with polycystic ovary syndrome." Archives of physiology and biochemistry 128(1): 37-42.
	Aim: We aimed to investigate the metabolic effects of HIIT exercise on PCOS patients and how it affects adiponectin, vaspin and leptin.; Material and Methods: Twenty women with PCOS were included in the study and were divided into two groups. HIIT program was applied for 10 PCOS and Medium Intensity Continuous Training (MICT) program was applied for other 10 PCOS. At the beginning and at the end of the study, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride(TG), insulin, Adiponectin, Leptin, Vaspin levels of both PCOS groups were evaluated.; Results: When PCOS patients by performed HIIT exercise for 12 weeks, we found that the levels of leptin and vaspin did not change while adiponectin levels increased. Moreover serum levels of insulin, TG, total cholesterol, LDL-C decreased but levels of HDL-C increased.; Conclusion: HIIT increased in the adiponectin levels in women with PCOS and provided more weight loss.

Akter, S., et al. (2023). "Melatonin enhances ovarian response in infertile women with polycystic ovary syndrome: A randomized controlled trial." Bangladesh Journal of Medical Science 22(4): 850-858.
	Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Anovulation, decreased Oocyte quality and low endometrial receptivity are the cause of infertility in women with PCOS. Anovulation is the consequence of hyperandrogenism, insulin resistance. Furthermore, the reactive oxygen species (ROS) induce oxidative stress which may be responsible for poor Oocyte quality. Melatonin is a documented powerful free radical scavenger and broad-spectrum antioxidant. Current evidence suggests that melatonin involves in ovarian physiology including follicular development, ovulation, and oocyte maturation. Present study was tried to evaluate the effects of melatonin on biochemical parameters as well as outcomes of ovulation induction by letrozole in infertile women with polycystic ovary syndrome. Method(s): This is a randomized controlled trial including 74 women of Polycystic Ovary Syndrome (PCOS) with infertility. Intervention group received melatonin 3 mg at bed time for 8 weeks as pretreatment. Serum luteinizing hormone (LH), testosterone, anti mullerian hormone (AMH), fasting insulin, oral glucose tolerance test (OGTT) were measured at baseline and after 8 weeks. Both intervention and controlled group were received ovulation induction for 3 cycles by Letrozole (5 mg from cycle days 2 to 6). Intervention group continued melatonin until mature follicle achieved. The primary outcomes were biochemical changes by serum luteinizing hormone (LH), testosterone, anti mullerian hormone (AMH), fasting insulin, oral glucose tolerance test (OGTT) and ovarian responses by number of mature follicles, endometrial thickness and ovulation rate. Secondary outcome was pregnancy rate. Result(s): Melatonin treatment for 8 weeks significantly decreased testosterone (P <0.01) serum luteinizing hormone (<P.001), HOMA IR (P<0.01) and glucose tolerance (P<0.01). The change of anti mullerian hormone was not significant (>0.05). There was significant difference in number of mature follicles (< 0.01), mean endometrial thickness (P<0.01). The risk ratio (RR) of ovulation rate was 1.34(0.09-1.68) and pregnancy rate was 2.55 (.37-3.51). The risk ratio (RR) of pregnancy rate in relation to AMH level was 1.12(0.05-1.79) in <=8ng/ ml group and 8.65(0.25-9.59) in >=8ng/ml group which was significant. Conclusion(s): After 8 weeks pretreatment and 3 cycle's co treatment with ovulation induction by letrozole, melatonin seems to provide improved biochemical and ovarian response. Based on these results, melatonin could be considered as a potential therapeutic agent for infertile women with polycystic ovary syndrome.Copyright © 2023, Ibn Sina Trust. All rights reserved.

Al Qurashi, A. A., et al. (2022). "The effects of bariatric surgery on male and female fertility: A systematic review and meta-analysis." Annals of Medicine and Surgery 80: 103881.
	
Ala, S., et al. (2022). "Efficacy of Omega-3, -6, and -9 Fatty Acids, Alone or in Combination With Low Dose Aspirin, in Improvement of Uterine Blood Flow in Women With History of Recurrent Miscarriage: A Prospective, Randomized, Clinical Trial." Pharmaceutical and Biomedical Research 8(1): 43-52.
	Background: Much evidence suggests that increased uterine blood flow resistance (reduced uterine perfusion) raises the risk of Recurrent Miscarriage (RM). Objective(s): This study aimed at evaluating the efficacy of omega-3, -6, and -9 fatty acids, alone or in combination with aspirin, in reducing uterine blood flow resistance in women with a history of RM. Method(s): A total of 45 women with a history of two or more miscarriages and increased uterine artery blood flow resistance were included in this randomized clinical trial. They were randomly assigned to aspirin (80 mg/d) (group A, n=15), omega-3, -6, and -9 fatty acids (4800 mg/d) (group O, n=15), or combination therapy (group AO, n=15). The patients were visited after two months, and the uterine artery blood flow resistance was measured by Doppler sonography. Result(s): The Mean+/-SD age of participants was 32+/-3.5 years in group A, 32+/-3 years in group O, and 32.4+/-3 years in group AO. There was no significant difference between three groups in age (P=0.7), duration of marriage (P=0.55), duration of infertility (P=0.43) and number of previous miscarriages (P= 0.51). In all three groups, after two months of treatment, the average uterine artery blood flow resistance reduced considerably compared with the beginning of the trial (P=0.0001); however, there was no significant difference between the three groups (P=0.56). Conclusion(s): According to the study results, omega-3, -6, and -9 fatty acids can reduce uterine artery blood flow resistance and improve the uterine blood flow in women with RM, with equal efficacy to aspirin. Also, combination therapy offers no advantages over monotherapy.Copyright © 2020, The Authors.

Alabiad, M. A., et al. (2022). "Evaluation of Different Doses of the Aromatase Inhibitor Letrozole for the Treatment of Ectopic Pregnancy and Its Effect on Villous Trophoblastic Tissue." Reproductive Sciences 29(10): 2983-2994.
	Letrozole, an aromatase inhibitor, has recently been introduced as a favorable medical treatment for ectopic pregnancy. We aimed at evaluating the effects of different doses of letrozole for termination of ectopic pregnancy and study their effects on villous trophoblastic tissue. Sixty patients with undisturbed ectopic pregnancy were classified into three equal groups. Group I: the control group that contained women who underwent laparoscopic salpingectomy, Group II: patients who received letrozole (5 mg day-1) for 10 days, and Group III: patients who received letrozole (10 mg day-1) for 10 days. Subsequently, the beta-hCG levels were determined on the first day and after 11 days of treatment. Group IV consisted of patients of GII and GIII; their beta-hCG did not drop below 100 mIU/ml within 11 days, and underwent salpingectomy. Placental tissues from patients undergoing salpingectomy either from the control group or GIV were processed for the evaluation of estrogen (ER) and progesterone (PR) receptors, vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC-3) expression. Cases exposed to high dose letrozole 10 mg day-1 resulted in a higher ectopic pregnancy resolution rate of 85% (17/20), while the resolution rate of the low dose letrozole-treated group (5 mg day-1) was 65% (13/20), and also showed a significant reduction in beta-hCG levels on the 11th day, 25.63 +/- 4.29 compared to the low dose letrozole group 37.91 +/- 7.18 (P < 0.001), Meanwhile, the letrozole-treated group GIV showed markedly reduced expression of ER, PR, and VEGF and a significant increase in the apoptotic index cleaved caspase-3 compared to the control group (P < 0.001). The utilization of letrozole at a dose of 10 mg day-1 for medical treatment of ectopic pregnancy results in a high-successful rate without any severe side effects. Letrozole depriving the placenta of estrogen that had vascular supporting signals resulted in destroying the vascular network with marked apoptosis. Graphical abstract: [Figure not available: see fulltext.]Copyright © 2022, The Author(s).

Alamolhoda, S. H., et al. (2022). "The Effect of Herbal Medicines on Treatment of Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis." Iranian Journal of Obstetrics, Gynecology and Infertility 25(10): 81-93.
	Introduction: Vasomotor symptoms during menopause occur on average in 75% of women. Hot flashes are the most common of these symptoms. Hormonal drugs are the most effective method of treatment. Due to the known risks of hormone therapy, many researchers have investigated the effect of herbal medicines to improve vasomotor symptoms, especially hot flashes. This study was performed with aim to investigate the clinical trial studies conducted on the effectiveness of various herbal medicines on hot flashes. Method(s): In this study, to find the related articles, databases of Google scholar, Scopus, PubMed, Web of science, Science direct and national databases such as (MagIran), (SID), (IranDoc) and (IranMedex) were searched from the beginning of January 2005 to January 2020. Data were combined using STATA software (version 12.2) and using meta-analysis method, random effects model. Result(s): In the present study, 11 clinical trials were included in the meta-analysis according to the inclusion criteria.In the medicinal plants group, mean reduction in the number of hot flushes was 2.41 times (95% CI: -1.56 to -3.27%) less than the control group, which was statistically significant (p<0.05).In addition, in the medicinal plants group, the intensity of hot flashes was 20.28 degrees (95% CI: -71.70 to -22.87) compared to the control group, and this difference was statistically significant (p<0.05). Conclusion(s): Medicinal plants containing phytoestrogens have good effects on reducing the frequency and intensity of hot flashes in menopausal women and can be a suitable treatment for hot flashes in menopausal women.Copyright © 2022, Mashhad University of Medical Sciences. All rights reserved.

Alan, U., et al. (2022). "Pharmacy role in the promotion of continence: a systematic review."
	
Alanwar, A. M., et al. (2022). "Maternal and Fetal Outcomes after Use of Lactoferrin in Prevention of Recurrent Bacterial Vaginosis in Pregnancy." NeuroQuantology 20(15): 7809-7815.
	Background: The most prevalent cause of vaginal discomfort in women is bacterial vaginosis (BV). It is characterised by an aberrant vaginal microbiota, which is predominately Gardnerellavaginalis and Atopobiumvaginae with a depletion of lactobacilli. Antibiotics are a short-term therapeutic approach that works well, but recurrent infections continue to be a severe issue that worsens maternal and foetal outcomes. Using probiotics effectively for the management of BV with better results is now supported by data. Aim of Study: To assess the maternal and fetal outcome after treatment with lactoferrin in patients with recurrent bacterial vaginosis in third trimester singleton pregnancy. Patients and method: This study was Randomized controlled clinical trial conducted at Obstetrics and Gynecology department, Zagazig University,outpatient clinic, included 66 cases with history of receurent bacterial vaginosis divided into two groups; study group: Lactoferrin (two capsules per day for five days, then one capsule per day for ten days) was administered orally. (pravotinR). Lactoferrin was not given to the control group. Throughout the follow-up phase, all women took 1 capsule of lactoferrin or placebo each day for 10 days per month. Result(s): Low APGAR1, preterm, CS delivery type, LBW and PROM were significantly higher with control group. Conclusion(s):In patients with bacterial vaginosis, repeated rounds of probiotics taken by mouth in conjunction with lactoferrin improved maternal and foetal outcomes.Copyright © 2022, Anka Publishers. All rights reserved.

Alba, M., et al. (2021). "Pelvic floor strengthening in non-specific lumbopelvic pain. Systematic review and meta-analysis."
	
Albahlol, I. A. (2021). "Cervical pregnancy management: An updated stepwise approach and algorithm." Journal of Obstetrics and Gynaecology Research 47(2): 469-475.
	The aim of this short review was to present and categorizes most of updated successful interventions for cervical pregnancy (CP) management in a simple designed easily recognized diagram together with a proposed algorithm of these interventions beside author clinical experience. A comprehensive literature search was carried out in the following electronic databases, PubMed, Scopus, Embase, Google Scholar, Directory of Open Access Journals and Cochrane electronic databases. Keywords including cervical ectopic pregnancy, medical treatment, conservative management, successful interventions, uterine artery embolization and hysteroscopy were used to search these various databases. There are different successful CP management interventions reported in the literature varied from simple to complex regimens according to the patient situation, obstetrician experience and availability of health services. These approaches were categorized in a stepwise diagram and a proposed algorithm. Up till now, there is no consensus regarding the optimal CP management. To the best of knowledge, this review was unprecedented in organizing and categorizing the different successful CP management interventions. The proposed currently undertaken stepwise approach diagram and algorithm highlights the rapidly changing management of CP and open the door for further meta-analysis.Copyright © 2020 Japan Society of Obstetrics and Gynecology

Albaladejo-Belmonte, M., et al. (2023). "Changes in pelvic floor electrical activity and vulvar pain after botulinum toxin treatment of vestibulodynia: are clinical and electrophysiological outcomes related?" Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 2023: 1-4.
	Vestibulodynia is a gynecological condition with different treatment options available, including botulinum neurotoxin type A (BoNT/A) injections into the vulvar vestibule. Unlike other treatments, no studies have assessed changes in the myoelectrical activity of the pelvic floor muscles (PFM) after BoNT/A treatment. The aim of this study was thus to evaluate these changes and to correlate them with changes in vulvar pain sensitivity. To do this, 35 patients with vestibulodynia were recruited, the myoelectrical activity of their left and right PFM was recorded with surface electromyography (sEMG), and their vulvar pain sensitivity was monitored according to Visual Analogue Scale (VAS) and an algometer, both before and after BoNT/A treatment. According to our results, patients' signals during PFM relaxation showed a significantly higher power than those of healthy women at baseline, as shown by their root mean square values (RMS), but became similar at follow-up. Patients' mean vulvar pain VAS scores significantly decreased after treatment. Furthermore, baseline-to-follow-up differences of RMS at PFM rest vs. mean VAS were significantly correlated (CC=0.48, p<0.01) so that higher reductions in the PFM activity power were associated with higher decreases in vulvar pain.Clinical Relevance- Altered PFM electrophysiological condition of patients with vestibulodynia becomes similar to healthy women's after BoNT/A treatment. This study also points to a relationship between the evolution of clinical and PFM electrophysiological conditions.

Al-Bayyari, N., et al. (2021). "Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial." Clinical nutrition (Edinburgh, Scotland) 40(3): 870-878.
	BACKGROUND & AIM: The objective of this study was to investigate the effect of vitamin D treatment on androgen levels and hirsutism scores in overweight women with PCOS. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical study was conducted at King Abdullah University Hospital in Irbid, Jordan. Overweight Jordanian females aged 18-49 years with vitamin D deficiency and PCOS (n = 60) were assigned to two groups: the treatment group (n = 30) who received 50,000 IU per week of vitamin D3 and the control group (n = 30) who received a placebo. RESULTS: After receiving the treatment for 12 consecutive weeks, the levels of total testosterone, parathyroid hormone, free androgen index, and hirsutism score were significantly decreased (P < 0.001), and the levels of 25-hydroxyvitamin D (25(OH)D), sex hormone binding globulin, and phosphorus were significantly increased (P < 0.05). Furthermore, significant changes were observed in ovarian volume and follicle numbers and size ultrasonography, and in the regularity of the menstrual cycle (P < 0.001). In the placebo group, no significant changes were observed in either androgen levels, hirsutism score, or menstrual regularity. CONCLUSION: Vitamin D3 at a treatment dose of 50,000 IU per week improved 25(OH)D levels and decreased the hirsutism scores and androgen levels of overweight women with PCOS. These results could mean increased fertility and better reproductive health for overweight women with PCOS; the use of vitamin D3 as a treatment for these patients should be further investigated. CLINICALTRIALS. GOV REGESTRATION NUMBER: NCT02328404.

Alberta University, o. (2024). Mindfulness in High Risk Pregnancies.
	No Results Available Behavioral: Mindfulness Change in stress symptoms|Change in anxiety symptoms|Change in depression symptoms|Change in mindful awareness|Mindfulness practice|Gestational age Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care Pro00102522 June 2025

Alboni, C., et al. (2023). "Robotic Surgery and Deep Infiltrating Endometriosis Treatment: The State of Art." Clinical and Experimental Obstetrics and Gynecology 50(1): 13.
	Objective: Surgical treatment of endometriosis, when indicated, has demonstrated to be effective in reducing painful symptoms and improve quality of life of patients affected with endometriosis. The minimally invasive approach via laparoscopy is the preferred method when compared with laparotomy but in the last two decades another minimally invasive approach has become available, the robotically assisted laparoscopic surgery. Robotic technology is widely used in different surgical branches, such as general surgery and urology. Moreover, the use of robotic surgery is already accepted for different gynecological procedures either for benign and for oncological diseases. The advantages of robotic surgery such as improve dexterity of movements, avoided tremor, increased magnification of 3-dimensional vision seem strategic in the context of a complex surgery as is deep endometriosis eradication. However, to date there is no unanimous consensus on whether robotically assisted procedures are a valid and safe alternative to laparoscopy in the treatment of endometriosis. Mechanism: In this narrative review we analyze the available literature assessesing the robotic treatment of all types of endometriosis and specifically deep infiltrating endometriosis, compared to the outcomes of conventional laparoscopy. Findings in Brief: Indeed, the evidence of safety and effectiveness of robotically assisted laparoscopy in endometriosis treatment is strong and almost unanimous. There is no clear superiority of one approach to the other but robotic-related advantages and future prospective are promising to be able to improve operative outcomes, reduce surgeon's fatigue and provide a technology easy to implement with a fast learning curve. Conclusion(s): Robotic technology applied to laparoscopy in the treatment of endometriosis could be seen as an effective and safe alternative to the conventional laparoscopic treatment.Copyright © 2023 The Author(s). Published by IMR Press.

Alborov, D. K., et al. (2023). "Therapeutic physical factors in chronic inflammatory diseases of the pelvic organs. (A wounded home-controlled study)." Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury 100(6): 52-58.
	
Alborzi, S., et al. (2023). "Approach to ureteral endometriosis: A single-center experience and meta-analysis of the literature." The Journal of Obstetrics and Gynaecology Research 49(1): 75-89.
	Aim: To report single-center outcomes of laparoscopic management of patients with ureteral endometriosis and perform a meta-analysis in order to select the best approach for these patients.; Methods: The cross-sectional study was conducted during a 6-year period (2015-2021) in the referral endometriosis center on 353 patients with ureteral endometriosis. For the meta-analysis, 10 articles, including 505 patients, were found to be eligible. In our meta-analysis, as well as our study, all endometriosis-related pain symptoms and complications of surgery were evaluated, analyzed, and reported.; Results: Of the 326 patients whose ureteral involvement was confirmed in pathology, hydronephrosis and intrinsic ureteral lesions were detected in only 10.76% and 3.1% of the patients. Mean operating time and hospitalization were 3.25 ± 1.83 h and 86 ± 2.58 days, respectively. The most common site of concomitant involvement with endometriosis was uterosacral ligament (92.9%) and rectosigmoid (70.53%). Type II and III of Cliven-Dindo complications were seen in 5.66% and 1.13% of patients, respectively. During a follow-up period, no evidence of bladder or ureteral re-involvement was observed. Similar to our meta-analysis, all endometriosis-related pain decreased significantly following operation (p ≤ 0.001). In our meta-analysis, the rate of ureteral endometriosis recurrence, stenosis/stricture, bladder atonia, urinary tract infection, hematuria, and fistula formation after surgery were: 2.0% (I 2 : 50.42%), 15.0% (I 2 : 0.00%), 14.0% (I 2 : 8.76%), 6.0% (I 2 : 0.00%), 7.0% (I 2 : 79.28%), and 2.0% (I 2 : 0.0%), respectively.; Conclusion: The laparoscopic resection of the UE could be suggested as a feasible and safe method associated with favorable functional outcomes. (© 2022 Japan Society of Obstetrics and Gynecology.)

Alborzi, S., et al. (2022). "The effect of vasopressin injection on ovarian reserve in patients with ovarian endometrioma: a randomized controlled trial." Reproductive Biomedicine Online 44(4): 651-658.
	Research Question: Does injecting vasopressin into the mesovarium during endometrioma cystectomy further preserve postoperative ovarian reserve by reducing intraoperative bleeding and electrocoagulation points?; Design: Randomized controlled trial conducted between March 2016 and March 2020. One hundred and twenty patients with unilateral and unilobulated endometrioma were included and divided into two groups: group 1 (n = 60) comprised all patients with ovarian cystectomy after vasopressin injection in the mesovarium space; group 2 included the controls. In both groups, the anti-Müllerian hormone (AMH) concentration was examined before surgery and 3, 6 and 12 months after surgery. In both groups, the number of bipolar cauterization points and the amount of bleeding during cystectomy as well as the pain symptoms related to endometriosis and pregnancy rate were further assessed and compared.; Results: Compared with the vassopressin group, the controls had significantly higher haemostasis points and bleeding (P = 0.0001). No significant difference was found between the two groups in serum AMH concentration at 3, 6 and 12 months after surgery. A significant reduction in pain symptoms was reported in both groups 6 months after surgery (P = 0.0001). No significant difference was found between the two groups in spontaneous pregnancy, miscarriage rate and pregnancy time after surgery.; Conclusion: Despite the reduction in the amount of bleeding and electrocoagulation points in the vasopressin group, ovarian reserve had a similar downward trend in both groups, which is attributed to the nature of these cysts. (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Alborzi, S., et al. (2019). "The success of various endometrioma treatments in infertility: A systematic review and meta-analysis of prospective studies." Reproductive Medicine and Biology 18(4): 312-322.
	Background: Endometriosis is seen in 0.5%-5% of fertile and 25%-40% of infertile women. To investigate this conflict between gynecologists that ovarian endometriomas should be removed or not before making any decision about pregnancy among infertile women, the authors decided to carry out a systematic review and meta-analysis to compare the effect of various available therapeutic methods and notice the impact of these options on women's pregnancy rate.; Methods: This review is based on PRISMA recommendations with an electronic search using the following databases: PubMed, Scopus, Google scholar, etc, from 2000 to 2018, in the English language. The studies compare pregnancy rate based on four different treatment types of OMAs between infertile women: (surgery + ART, surgery + spontaneous pregnancy, aspiration ± sclerotherapy + ART, and ART alone).; Main Findings: At least eight prospective studies were included, in which 553 infertile women were compared in terms of treatment methods of OMAs before trying to become pregnant.; Conclusion: Treatments are usually based on the patient's clinical condition and must be individual, with the purpose of relieving pain, improving fertility, or both. The authors do not have not any significant difference between our four groups of study; however, the success of surgical procedure compared to other methods was higher and the success of ART alone was the least.; Competing Interests: Conflict of interest: Saeed Alborzi, Ziba Zahiri Sorouri, Elham Askari, Tahereh Poordast, and Kefayat Chamanara declare that they have no conflict of interest. Human/animal rights statements and informed consent: This article does not contain any studies with human and animal patients performed by any of the authors. (© 2019 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Albright, B. B., et al. (2023). "Treatments and outcomes in high-risk gestational trophoblastic neoplasia: A systematic review and meta-analysis." BJOG: An International Journal of Obstetrics and Gynaecology 130(5): 443-453.
	Background: High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed. Objective(s): To compile global high-risk GTN (prognostic score >=7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy. Search Strategy: MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021. Selection Criteria: Full-text manuscripts reporting mortality among >=10 high-risk GTN patients. Data Collection and Analysis: Binomial proportions were summed, and random-effects meta-analyses performed. Main Result(s): From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%. Conclusion(s): High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.Copyright © 2023 John Wiley & Sons Ltd.

Albright Benjamin, B., et al. (2021). "Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis." American Journal of Obstetrics and Gynecology 225(3): 237.e231-237.e224.
	Objective: Endometrial cancer uncommonly presents at an advanced stage and little prospective evidence exists to guide the management thereof. We aimed to summarize the evidence about primary cytoreductive surgery in the treatment of advanced stage endometrial cancer.; Data Sources: MEDLINE, Embase, and Scopus databases were searched from inception to September 11, 2020, using search terms representing the themes "endometrial cancer," "advanced stage," and "primary cytoreductive surgery."; Study Eligibility Criteria: We included full-text, English reports that included ≥10 patients undergoing primary cytoreductive surgery for advanced stage endometrial cancer and that reported on the outcomes of primary cytoreductive surgery and survival rates based on the residual disease burden.; Methods: Two reviewers independently screened the studies and with disagreements between the reviewers resolved by a third reviewer. Data were extracted using a standardized form. The percentage of cases reaching maximal (no gross residual disease) and optimal (<1 cm or <2 cm residual disease) cytoreduction were assessed by summing binomials proportions, and the association with survival was assessed using an inverse variance-weighted meta-analysis of logarithmic hazard ratios.; Results: From 1219 unique records identified, 34 studies were selected for inclusion. Studies consisted of single or multi-institutional cohorts of patients collected over a period of 6 to 24 years and included various mixes of histologies (endometrioid, serous, clear cell, and carcinosarcoma) and disease stages (III or IV). In a meta-analysis of the extent of residual disease after primary cytoreductive surgery, we found that 52.1% of cases reached no gross residual disease status (n=18 studies; 1329 patients) and 75% reached <1 cm residual disease status (n=27 studies; 2343 patients). The proportion of cytoreduction for both thresholds was lower for studies of stage IV vs stage III to IV disease (41.4% vs 69.8% for no gross residual disease; 63.2% vs 82.2% for <1 cm residual disease) but did not vary notably by histology. In a meta-analysis of the reported hazard ratios, submaximal (any gross residual disease vs no gross residual disease) and suboptimal (≥1 cm vs <1 cm) cytoreduction thresholds were associated with worse progression-free survival (submaximal hazard ratio, 2.16; 95% confidence interval, 1.45-3.21; I 2 =68%; suboptimal hazard ratio, 2.55; 95% confidence interval, 1.93-3.37; I 2 =63%) and overall survival rates (submaximal hazard ratio, 2.57; 95% confidence interval, 2.13-3.10; I 2 =1%; suboptimal hazard ratio, 2.62; 95% confidence interval, 2.20-3.11; I 2 =15%). Sensitivity analyses limited to high-quality studies demonstrated consistent results.; Conclusion: Among cases of advanced stage endometrial cancer undergoing primary cytoreductive surgery, a significant proportion of patients are left with residual disease, which is associated with worse survival outcomes. Further investigations about the roles of neoadjuvant chemotherapy and primary cytoreductive surgery in prospective trials is warranted in this population. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Alcala University, o. (2021). Lumbar Spine Manipulation Versus Pharmacological Therapy in Young Women With Primary Dysmenorrhea.
	No Results Available Other: Lumbar spine manipulation|Drug: Hyoscine and Ibuprofen Pain intensity|Pressure pain threshold measured in tibialis malleolus|Pressure pain threshold measured in peroneal malleolus|Low-back related disability|Anxiety and depression Female Not Applicable 42 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 2111730 November 10, 2022

Alcala University, o. (2023). Multimodal Physiotherapy Based on Tele-rehabilitation in Chronic Pelvic Pain Associated With Endometriosis.
	No Results Available Other: TeleRehab Group|Other: Advices Group Health Status Questionnaire (SF-12)|Visual Numeric Scale (VNS)|Endometriosis Health Profile (EHP-30)|Index of Sexual Function (IFSF)|Tampa Scale of Kinesiophobia (TSK)|Pain Catastrophizing Scale (PCS)|Hospital Anxiety and Depression Scale (HADS)|International Physical Activity Questionnaire (IPAQ)|Pittsburg Sleep Quality Index (PSQI)|Perceived Stress Scale (PSS)|Patient's adherence will be evaluated|Patient global impression of change (PGI-I) Female Not Applicable 66 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment CEID/2023/6/106 January 17, 2027

Alcantarilla, L., et al. (2023). "Risk factors for relapse or recurrence in women with bipolar disorder and recurrent major depressive disorder in the perinatal period: a systematic review." Archives of Women's Mental Health 26(6): 737-754.
	It is well known that the perinatal period supposes a considerable risk of relapse for women with bipolar disorder (BD) and recurrent major depressive disorder (rMDD), with the consequences that this entails. Therefore, the authors sought to provide a critical appraisal of the evidence related to specific risk factors for this population with the aim of improving the prevention of relapses during pregnancy and postpartum. The authors conducted a systematic review assessing 18 original studies that provided data on risk factors for relapse or recurrence of BD and/or rMDD in the perinatal period (pregnancy and postpartum). Recurrences of BD and rMDD are more frequent in the postpartum period than in pregnancy, with the first 4-6 weeks postpartum being especially complicated. In addition, women with BD type I are at higher risk than those with BD type II and rMDD, and the most frequent presentation of perinatal episodes of both disorders is a major depressive episode. Other risk factors consistently repeated were early age of onset of illnesses, severity criteria, primiparity, abrupt discontinuation of treatment, and personal or family history of perinatal affective episodes. This review shows that there are common and different risk factors according to the type of disorder and to perinatal timing (pregnancy or postpartum) that should be known for an adequate prevention of relapses.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Aldrich, E. R., et al. (2022). "Impact of intrarectal diazepam on early postoperative pain following pelvic reconstructive surgery: a double-blind, randomized placebo-controlled trial." American Journal of Obstetrics and Gynecology 226(3 Supplement): S1277-S1278.
	Objectives: To evaluate the effect of diazepam rectal suppositories on early postoperative pain following hysterectomy and vaginal reconstruction for pelvic organ prolapse. Material(s) and Method(s): In this institutional review board approved, double-blind, randomized placebo-controlled trial, eligible patients were those scheduled to undergo a total vaginal hysterectomy with reconstructive surgery for prolapse. Consented patients were randomized to receive either a 10mg diazepam rectal suppository or an identical appearing placebo intraoperatively at the completion of surgery. Our primary outcome was vaginal pain 3.5-6 hours postoperatively utilizing the 100mm visual analog scale (VAS). Participants also completed surveys regarding pain at baseline, the morning of postoperative day (POD) one, and two-weeks postoperatively. Secondary outcomes included total morphine equivalents following surgery, patient satisfaction with pain control, and overall satisfaction. Chi-squared test, Fisher's exact test, and Mann-Whitney test were utilized. Our sample size calculation demonstrated that 55 patients per arm were required to detect a difference in our primary outcome. Result(s): From February 2020 to August 2021, 130 subjects were randomized. Seven patients withdrew, 113 have been analyzed to date; 57 in the diazepam group, 56 in placebo. The median age was 65 (IQR 27, 80), median BMI was 27.9 (IQR 18.70, 45.90), and 96.5% (n=109) of participants were white. There were no differences in baseline characteristics, prolapse stage, or types of procedures performed between groups. Ninety-nine percent (n=112) of participants had concurrent uterosacral ligament suspension, anterior and posterior repairs. Forty-one percent (n=46) had midurethral slings. Forty-five percent (n=51) had same-day discharge. There were no differences in the amount of intraoperative lidocaine injected (30.84 vs 30.16mL, p=0.679) or amount of rescue narcotics used in the immediate postoperative period (22.5 vs 16 morphine equivalents, p=0.286). There was also no difference in the primary outcome of VAS score for vaginal pain 3.5-6 hours postoperatively (24 vs 21mm, p=0.417). At their 2-week survey, patients in the placebo group reported higher satisfaction with pain control in the hospital (31 vs 41mm, p=0.012) and pain control at home (31 vs 40mm, p=0.043). No differences were noted among patients discharged on POD0 compared to those admitted overnight. Conclusion(s): In our population, placement of a 10mg Diazepam rectal suppository immediately following pelvic reconstructive surgery did not improve pain or narcotic usage in the early postoperative period. Although the placebo group reported slightly higher satisfaction with pain control two-weeks following surgery, overall pain levels were low. Therefore, we do not feel the addition of diazepam to the post-operative regimen is warranted.Copyright © 2022

Aleixo, G. F., et al. (2018). "Pelvic floor symptoms 5 to 14 years after total versus subtotal hysterectomy for benign conditions: a systematic review and meta-analysis." International Urogynecology Journal 30(2): 181-191.
	Introduction and hypothesis: We aim to compare total versus subtotal abdominal hysterectomy regarding urinary and bowel symptoms and pelvic organ prolapse at long-term follow-up. Method(s): A systematic literature search was performed on the MEDLINE, LILACS, Cochrane CENTRAL and SCOPUS databases and conference abstracts (AAGL, AUGS, ICS) from inception up to November 2017. We included randomized trials comparing total versus subtotal hysterectomy for benign conditions that evaluated pelvic floor symptoms over 5 years of follow-up. Risk of bias and GRADE assessment for quality of evidence were performed. Result(s): We included four studies involving 566 participants with follow-up ranging from 5 to 14 years. Women who underwent total hysterectomy presented lower risk of reported urinary incontinence [RR 0.74 (CI = 0.58, 0.94) i2 0%; p = 0.02] and stress urinary incontinence [RR 0.84 (CI = 0.71, 0.99) i2 0%; p = 0.04] than those who had subtotal hysterectomy. The events urinary frequency, urge incontinence, incomplete bladder emptying, pelvic organ prolapse, incontinence of stool and constipation did not favor one procedure over another in the long term (P > 0.05). Conclusion(s): Patient-reported urinary incontinence and stress urinary incontinence events favored total hysterectomy over subtotal hysterectomy up to 14-year long-term follow-up.Copyright © 2018, The International Urogynecological Association.

Alenzi, E. O. (2023). "Impact of Vitamin D Supplementation on Menstrual Cycle Irregularities among Women with Polycystic Ovary Syndrome who were Treated with Metformin: A Systematic Review with Meta-Analysis." Current Women's Health Reviews 19(4): 147-154.
	Background: There is inconsistency in the evidence about the effect of adding vitamin D supplements to metformin therapy among women with polycystic ovary syndrome (PCOS). Objective(s): In this systematic review, we described the differences in menstrual cycle irregularities between women who received vitamin D supplementation and those who didn't receive vitamin D among women who diagnosed with PCOS and received metformin. Method(s): We reviewed previous literature to identify all relevant studies. The included studies' quality and risk of bias were assessed using the Consolidated Standards of Reporting Trials (CONSORT) and the Reporting of Observational Studies in Epidemiology (STROBE) instrument. Cochrane's Q-test and I2 statistic were used to assess the heterogeneity across included studies. The fixed-effect model was used to calculate the total effect size. Result(s): Six studies were included, involving 633 women diagnosed with PCOS. Supplementation of vitamin D with metformin could have a significant impact on the improvement of menstrual cycles compared to receiving metformin alone (OR = 2.11, 95% CI, 1.40-3.19). There was no evidence of heterogeneity across included studies. Subgroup analysis showed that the magnitude of the association increased when only infertile women with PCOS were included (OR = 2.37, 95% CI, 1.52-3.72). Conclusion(s): This evidence suggests the possible benefit of adding vitamin D to metformin in regulating the menstrual cycle among women with PCOS, especially infertile women.Copyright © 2023 Bentham Science Publishers.

Alesi, S., et al. (2022). "Nutritional Supplements and Complementary Therapies in Polycystic Ovary Syndrome." Advances in nutrition (Bethesda, Md.) 13(4): 1243-1266.
	Polycystic ovary syndrome (PCOS) affects 1 in 5 women of reproductive age, and is characterized by menstrual irregularities, clinical or biochemical hyperandrogenism, and the presence of polycystic ovary morphology. One of the recommended treatment strategies in the international evidence-based guidelines is lifestyle modification, which includes diet and exercise, with the aim of improving a range of health outcomes. The incurable nature of PCOS reinforces the importance of developing novel and innovative symptomatic relief strategies, which are currently the only available approaches for improving quality of life for these women. Women with PCOS tend to be nutrient deficient in many common vitamins and minerals, thought to be associated with the psychological (depression, anxiety, etc.) and physiological (insulin resistance, diabetes, infertility, etc.) sequelae of the condition. Nutrient supplementation and the integration of complementary medicine as adjuncts to traditional lifestyle-based therapies in PCOS could therefore provide additional benefits to these women. In this review, we synthesize the evidence regarding nutrient supplementation and complementary therapies in PCOS, predominantly from randomized controlled trials, systematic reviews, and meta-analyses, to provide an overview of the state of knowledge in this field. The evidence to date suggests that specific vitamins (B-12, inositols, folate, vitamins D, E, and K), vitamin-like nutrients (bioflavonoids and α-lipoic acid), minerals (calcium, zinc, selenium, and chromium picolinate), and other formulations (melatonin, ω-3 fatty acids, probiotics, and cinnamon), as well as some complementary approaches such as acupuncture and yoga may be beneficial in PCOS. However, there remain areas of uncertainty and key limitations in the literature that must be overcome before these therapies can be integrated into routine clinical practice. (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Alesi, S., et al. (2023). "Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials." EClinicalMedicine 63: 102162.
	Background: Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS.; Methods: We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640.; Findings: From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n = 961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens + lifestyle were superior to metformin + lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]: -1.59 [-3.06, -0.12], p = 0.03; I 2 = 74%), SHBG (7.70 nmol/l [0.75, 14.66], p = 0.03; I 2 = 0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97, -0.26], p = 0.03; I 2 = 0% and -1.12 [-1.44, -0.79], p < 0.0001, I 2 = 0%, respectively), but were not superior to placebo + lifestyle for hirsutism (-0.93, [-3.37, 1.51], p = 0.45; I 2 = 76%) or SHBG (9.72 nmol/l [-0.71, 20.14], p = 0.07; I 2 = 31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58, -2.39], p < 0.0001, I 2 = 1%), and resulted in lower androstenedione levels (-0.30 ng/ml [-0.50, -0.10], p = 0.004; I 2 = 0%). Combination treatment with anti-androgens + metformin + lifestyle resulted in lower testosterone compared with metformin + lifestyle (-0.29 nmol/l [-0.52, -0.06], p = 0.01; I 2 = 61%), but there were no differences in hirsutism when anti-androgens + metformin + lifestyle were compared with either anti-androgens + lifestyle or metformin + lifestyle. In limited meta-analyses (n = 2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP ± placebo, with no differences in other outcomes.; Interpretation: Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics.; Funding: National Health and Medical Research Council (NH RC) of Australia Monash University.; Competing Interests: All authors declare no competing interests. JM received funding from the Orion Research Foundation and the Medical Society of Finland. MF received funding from the Gothenburg Medical Association, Sahlgrenska University H spital, the Iris Foundation and the Hjalmar Svensson Foundation, as well as honoraria from Gedeon Richter. HT received funding from the National Health and Medical Research Council (NHMRC) through the Centre for Research Excellence for Women's Health in Reproductive Life (CRE-WHiRL). SFW received support from the NHMRC-funded guideline to attend the guideline meeting and is a member of the board of directors for the Paediatric Endocrine Society. CTT is supported by CRE- WHiRL and chairs the Androgen Excess and Polycystic Ovary Syndrome Society Early Career Special Interest Group. None of these funding organisations had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors declare no competing interests. (© 2023 The Author(s).)

Alessandro, C., et al. (2022). "Intrauterine strategy to improve IVF outcome: a systematic review and meta-analysis."
	
Alessandro, C., et al. (2021). "Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis."
	
Alexander, A. T., et al. (2023). "Uterine artery embolisation versus myomectomy for the management of women with uterine leiomyomas."
	
Alexander, J., et al. (2022). "Carbon dioxide surgical laser for treatment of stress urinary incontinence in women: A randomized controlled trial." International Urogynecology Journal 33(Supplement 1): S64.
	Introduction: Stress urinary incontinence (SUI) is common with prevalence in most studies reported between 10-39%[1]. Bothersome SUI can be treated conservatively or surgically but there is a desire to develop effective non-surgical treatment options. Some studies have suggested laser therapy may improve or cure SUI[2]. The rationale for the use of CO2 laser for SUI is to trigger tissue remodelling and regeneration to improve urethral support and improve continence[3]. Objective(s): To evaluate CO2 laser versus shamfor the treatment of SUI in a RCT. Method(s): This was a multi-centre, prospective, single-blinded, shamcontrolled RCT. Participants were treated in the outpatient setting. Participants were aged 18-80 with symptomatic and objective SUI. Objective SUI was demonstrated with a positive cough stress test, urodynamic stress incontinence, or 24-hour pad weigh test (>4g). Participants had undertaken or declined supervised pelvic floor exercises. Intervention was performed using a CO2 fractionated vaginal laser to provide treatment. 7.5-12.5mJ with a 10-15% density, and a penetration depth of 600nm was delivered from the proximal vagina to 5mm from the introitus. Energy was delivered circumferentially to the entire vagina with one pass. An additional pass was performed at 10 o'clock and two o'clock. An additional two passes were performed at 12 o'clock. Participants underwent three treatments, 4 weeks apart, with increasing energy and density settings. The primary outcome was to assess the subjective cure rate (ICIQ-UI question 6c or 6e) of the CO2 surgical laser against sham 3 months after the completion of laser treatment. Secondary outcomes were to assess safety, subject discomfort, patient reported outcomes (PRO), quality of life (QOL) questionnaires (PGII, IIQ, PISQ, ICIQ OAB, ICIQ UI SF) and subject satisfaction 1 and 3 months after the last treatment. Based on previous data[4] we estimated a dry rate (ICIQ-UI SF=0) of 22% and 3% in laser and sham participants, respectively. - A sample size of 101 (including attrition) was calculated to provide 80% power (alpha=.05) to detect a difference between groups. Outcomes were compared using the chi-squared test for categorical data and student t test for continuous data. Differences in pre- and posttreatment changes between groups were assessed using analysis of covariance (ANCOVA). Result(s): 99 of 101 participants participated throughout the trial which commenced in April 2017 with the last treatment occurring in July 2020. Two further cases were excluded due to a delay in presentation posttreatment. Mean age was 53 years (34-79). Mean BMI was 26.1 (18.1- 49.6). 90% were vaginally parous. Baseline characteristics of the two groups are presented in table 1. 3 months post treatment, 48 (98%) participants in the laser arm, and 46 (96%) participants in the sham arm reported leak with cough, sneeze, or laughter (table 2), representing no difference. PRO and QOL outcomes were similar. Outcomes are presented in tables 2 and 3. There was no difference in mean pain VAS scores during treatment (1.6(laser) vs 1.1(sham), p=.26). There were no major complications confirmed during the trial Conclusion(s): CO2 vaginal laser therapy does not improve SUI compared to sham treatment in our population.

Alexander, J. W., et al. (2023). "CO2Surgical Laser for Treatment of Stress Urinary Incontinence in Women: A Randomized Controlled Trial." Obstetrical and Gynecological Survey 78(2): 101-103.
	
Alexandri, C., et al. (2020). "The role of microRNAs in ovarian function and the transition toward novel therapeutic strategies in fertility preservation: from bench to future clinical application." Human Reproduction Update 26(2): 174-196.
	Background: New therapeutic approaches in oncology have converted cancer from a certain death sentence to a chronic disease. However, there are still challenges to be overcome regarding the off-target toxicity of many of these treatments. Oncological therapies can lead to future infertility in women. Given this negative impact on long-term quality of life, fertility preservation is highly recommended. While gamete and ovarian tissue cryopreservation are the usual methods offered, new pharmacological-based options aiming to reduce ovarian damage during oncological treatment are very attractive. In this vein, advances in the field of transcriptomics and epigenomics have brought small noncoding RNAs, called microRNAs (miRNAs), into the spotlight in oncology. MicroRNAs also play a key role in follicle development as regulators of follicular growth, atresia and steroidogenesis. They are also involved in DNA damage repair responses and they can themselves be modulated during chemotherapy. For these reasons, miRNAs may be an interesting target to develop new protective therapies during oncological treatment. This review summarizes the physiological role of miRNAs in reproduction. Considering recently developed strategies based on miRNA therapy in oncology, we highlight their potential interest as a target in fertility preservation and propose future strategies to make the transition from bench to clinic.; Objective and Rationale: How can miRNA therapeutic approaches be used to develop new adjuvant protective therapies to reduce the ovarian damage caused by cytotoxic oncological treatments?; Search Methods: A systematic search of English language literature using PubMed and Google Scholar databases was performed through to 2019 describing the role of miRNAs in the ovary and their use for diagnosis and targeted therapy in oncology. Personal data illustrate miRNA therapeutic strategies to target the gonads and reduce chemotherapy-induced follicular damage.; Outcomes: This review outlines the importance of miRNAs as gene regulators and emphasizes the fact that insights in oncology can inspire new adjuvant strategies in the field of onco-fertility. Recent improvements in nanotechnology offer the opportunity for drug development using next-generation miRNA-nanocarriers.; Wider Implications: Although there are still some barriers regarding the immunogenicity and toxicity of these treatments and there is still room for improvement concerning the specific delivery of miRNAs into the ovaries, we believe that, in the future, miRNAs can be developed as powerful and non-invasive tools for fertility preservation. (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Alexey, R., et al. (2022). "Platinum vs non-platinum chemotherapy for platinum-resistant ovarian cancer: a systematic review and meta-analysis." MedRxiv.
	Background: recurrent ovarian cancer (OC) patients with platinum-free interval (PFI) <6 mo. are usually considered platinum-resistant and treated with non-platinum based chemotherapy. However, this was never confirmed in proper-conducted randomized trials. Method(s): we queried the PubMed database for all full-text articles and abstracts on the treatment of patients with platinum-resistant ovarian cancer (PROC) in 01/01/2000-01/06/2019 timeframe. The PRISMA tool was used to ensure transparent reporting of the results. Inclusion criteria were: 1) morphologically confirmed epithelial ovarian cancer; 2) recurrent disease within 6 months after completion of platinum-based chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy with agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents or non-platinum doublets; 5) defined response rate (RR) and assessment criteria. Proportion meta-analysis (random-effect model) and beta-regression were conducted to assess the impact of platinum agents on response rate as well as significance of other variables. In the beta-regression model response rate was a dependent variable, while platinum agents (yes or no), used non-platinum drugs and method of response assessment were independent variables. Statistical analysis was dose with meta, metafor and betareg packages of R software. Result(s): we identified 7156 articles and screened them for title and abstract, 157 studies for further analysis. Overall, 6327 patients were included in the analysis, efficacy of non-platinum- and platinum-based therapy was assessed in 113 (n = 5272) and 44 (n = 1055) trials respectively. In meta-proportion random-effect model RR among patients treated with platinum-based and non-platinum chemotherapy RR was 36% (95% CI 30-41; I2 = 62%) and 16% (95% CI 14-19; I2=70%) respectively. For sensitivity analysis various regression models were made with different subsets of the trials and additional variables (including year of the trial, percentage of serous subtype of OC and median of prior therapy lines). Platinum was the strongest predictor of response in every developed model. Conclusion(s): this meta-analysis shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents. These results support recent ESMO-ESGO consensus on treatment of recurrent ovarian cancer .Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

Alfahmy, A., et al. (2021). "Abdominal and vaginal pelvic support with concomitant hysterectomy for uterovaginal pelvic prolapse: a comparative systematic review and meta-analysis." International Urogynecology Journal 32(8): 2021-2031.
	Introduction and Hypothesis: While approximately 225,000 pelvic organ prolapse (POP) surgeries are performed annually in the US, there is no consensus on the optimal route for pelvic support for the initial treatment of uterovaginal prolapse (UVP). Our objective is to compare the outcomes of abdominal sacrocolpopexy (ASC) to vaginal pelvic support (VPS) with either uterosacral ligament suspension (USLS) or sacrospinous ligament fixation (SSF) in combination with hysterectomy for treating apical prolapse.; Methods: A systematic search was performed through March 2021. Studies comparing ASC with VPS for treatment of UVP were included in the review. The primary outcome was the rate of overall anatomic prolapse failure per studies' definition. Secondary outcomes included evaluating isolated recurrent vaginal wall prolapse, postoperative POP-Q points, total vaginal length (TVL), and Pelvic Floor Distress Inventory (PFDI-20) scores. Random effect analyses were generated utilizing R 4.0.2.; Results: Out of 4225 total studies, 4 met our inclusion criteria, including 226 patients in the ASC group and 199 patients in the VPS group. ASC was not found to be associated with a higher rate of vaginal wall prolapse recurrence (OR = 0.6; 95% CI = 0.2-2.4; P = 0.33). There was no significant difference between groups for anterior or apical vaginal wall prolapse recurrence (P = 0.58 and P = 0.97, respectively). ASC was associated with significantly longer TVL (mean difference [MD]: 1.01; 95% CI = 0.33-1.70; P = 0.02) and better POP-Q Ba scores [MD = -0.23; 95% CI = -0.37; -0.10; P = 0.01].; Conclusions: ASC and vaginal pelvic support (either USLS or SSF) have comparable anatomical outcomes. However, weak evidence of a difference in TVL and Ba was found. The strength of the evidence in this study is based on the small number of observational studies. A large, randomized trial is highly warranted. (© 2021. The International Urogynecological Association.)

Alfayumi-Zeadna, S., et al. (2022). "A Non-Randomized Controlled Trial for Reducing Postpartum Depression in Low-Income Minority Women at Community-Based Women's Health Clinics." Maternal and Child Health Journal 26(8): 1689-1700.
	Objective: To analyze an intervention that delivered tailored clinic staff training on postpartum depression (PPD) followed by awareness raising and social support aimed at lowering PPD among low-income Bedouin women in southern Israel.; Methods: We conducted a non-randomized controlled trial at two women's health clinics. The study included 332 of the 384 eligible women recruited at baseline (intervention = 169, control = 163), who completed two face-to-face interviews, one at 26-38 weeks of pregnancy (Time 1) and one 2-4 months postpartum (Time 2). PPD was measured by the Edinburgh Postnatal Depression Scale (EPDS) and dichotomized using a ≥ 10 score cutoff. We calculated EPDS change (rate difference of dichotomous EPDS from Time 1 to Time 2) (no change, positive change, or negative change), and compared EPDS changes in a control clinic vs. an intervention clinic.; Results: The intervention group showed a greater decrease in dichotomous EPDS ≥ 10 between times 1 and 2 (38.5% to 17.2%) than the control group (31.9% to 29.4%, PV = 0.008). Multinomial logistic regression showed that high PPD awareness significantly contributed to positive EPDS change in the intervention group (PV = 0.003) and high social support significantly protected against negative EPDS change in both groups, intervention (PV = 0.001) and control (PV = 0.003).; Conclusions: In low-income women, an intervention focusing on increasing PPD awareness and social support following staff training was associated with reduced EPDS and positive EPDS change following the intervention. Similar interventions should be implemented in women's clinics during pregnancy.; Clinical Trial Registry: ClinicalTrials.gov NCT02862444. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alfrink, J., et al. (2024). "Radiochemotherapy and interstitial brachytherapy for cervical cancer: clinical results and patient-reported outcome measures." Strahlentherapie und Onkologie.
	Objective: To evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment. Material(s) and Method(s): Between 2003 and 2023, a total of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46 patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients' self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires. Result(s): Five-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. A significant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB-IIIA: 79% vs. IIIB-IVA: 33%, p= 0.015), for overall treatment time (OTT; 50-65 d: 64% vs. >65 d: 38%, p= 0.004), and for rectal D2cc (<=73Gy: 50% vs. >73Gy: 38%, p= 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p= 0.012, OTT: p= 0.008, D2cc: p= 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p= 0.05) and DMFS (p= 0.014) was detected, and of rectal D2cc on DMFS (p= 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded. Conclusion(s): In patients with advanced cervical cancer, a combination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity.Copyright © 2024, The Author(s).

Algera, M. D., et al. (2022). "Surgical treatment for clinical early-stage expansile and infiltrative mucinous ovarian cancer: Can staging surgeries safely be omitted?" Current Opinion in Oncology 34(5): 497-503.
	Purpose of reviewMucinous ovarian cancers (MOCs) are categorized into infiltrative and expansile subtypes. These subtypes have different characteristics and prognoses. Patients with clinical early-stage disease of both subtypes currently undergo surgical staging (peritoneal washing, biopsies, omentectomy). Peritoneal and lymph node metastases of expansile MOC are rare, but whereas lymph node sampling (LNS) is omitted in these patients, peritoneal staging is not. Therefore, we collected all available MOC data to determine whether staging surgeries could safely be omitted in clinical early-stage expansile and infiltrative MOC.Recent findingsCurrent literature confirms that peritoneal metastases are rare in expansile MOC: more than 90% of patients have early-stage disease. Only 3.4% of the patients with clinical early-stage expansile MOC had positive peritoneal washings at surgical staging. Patients with infiltrative MOC were diagnosed more frequently with advanced-stage disease (21-54%). Moreover, upstaging clinical early-stage infiltrative MOC based on positive cytology, peritoneum and omentum metastases occurred in 10.3% of the patients. Therefore, we recommend that patients with early-stage infiltrative MOC undergo peritoneal staging and LNS. However, in addition to omitting LNS, we can also safely recommend omitting peritoneal staging in patients with clinical early stage expansile MOC.SummaryPeritoneal metastases are rare in clinical early-stage expansile MOC and peritoneal staging can therefore safely be omitted.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Al-Hendy, A., et al. (2021). "ASSESSMENT OF COMMON ADVERSE EVENTS OF RELUGOLIX COMBINATION THERAPY IN PREMENOPAUSAL WOMEN TREATED FOR SYMPTOMATIC ESTROGEN-DRIVEN CONDITIONS: LIBERTY AND SPIRIT STUDIES." Fertility and Sterility 116(3): e11.
	Objective: Relugolix is a once‐daily, oral nonpeptide gonadotropin‐releasing hormone receptor antagonist being developed in combination with estradiol (E2) and norethindrone acetate (NETA) to treat heavy menstrual bleeding (HMB) associated with uterine fibroids (UF) and moderate‐to‐severe pain associated with endometriosis (EM). In the Phase 3 LIBERTY 1/2 trials for UF (n=770), relugolix combination therapy (Rel‐CT [once‐daily relugolix 40 mg, E2 1 mg, NETA 0.5 mg]) reduced HMB vs placebo. In the SPIRIT 1/2 trials for EM (n=1251), Rel‐CT reduced dysmenorrhea, non‐menstrual pelvic pain and dyspareunia vs placebo. A pooled population assessment was undertaken to define an adverse event profile of Rel‐CT in premenopausal women. Materials and Methods: The common adverse event profile of Rel‐CT was assessed based on adverse events (AEs) observed at a frequency of ≥ 2% for Rel‐CT and higher than in placebo reported over 24 weeks in the pivotal studies. All AEs included were coded to preferred term (PT) and system organ class (SOC) using the global Medical Dictionary for Regulatory Activities (MedDRA) version 22.0 or higher. Results: There were 1344 patients in the pooled assessment from the 24‐week LIBERTY and SPIRIT studies. The most common AEs with Rel‐CT were headache (24.3%) and hot flush (10.6%) vs placebo (21.4% and 6.4%, respectively). Other AEs consistently observed in both populations included relevant terms of the reproductive tract, libido decrease and vasomotor symptoms (Table). Specifically for the UF population, AEs reported in at least 2% of women in the Rel‐CT group and at greater incidence than placebo included alopecia, irritability, dyspepsia, and breast cyst. Those reported for the EM population included nausea, back pain, arthralgia and vulvovaginal dryness. [Formula presented] a Includes menorrhagia, metrorrhagia, uterine hemorrhage, genital hemorrhage, and vaginal hemorrhage. SOC – System Organ Class, PT – Preferred Term Conclusions: In premenopausal women with UF or EM, Rel‐CT was well tolerated with a common adverse event profile representative of both populations. Impact Statement: An integrated adverse event profile for women with UF and EM may allow better understanding of the consistent risk profile of Rel‐CT in premenopausal women, for physicians and patients.

Al-Hendy, A., et al. (2022). "Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas." Obstetrics and Gynecology 140(6): 920-930.
	Objective: In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.; Methods: Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.; Results: Overall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.; Conclusion: Improvements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.; Clinical Trial Registration: ClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.; Funding Source: Myovant Sciences GmbH.; Competing Interests: Financial Disclosure Ayman Al-Hendy has been a Consultant for AbbVie, Bayer, Myovant Sciences, and ObsEva. They have received Research Support from the National Institutes of Health (R01 ES 028615–01, R01HD 087417, R01 HD 094378, R01 HD 094380, R01 HD 10036701, U54 MD 007602) and hold a patent for methods for novel diagnostics and therapeutics for uterine sarcoma (US Pat No. 9,790,562 B2). Andrea Lukes received research support from AbbVie, Astellas, Bayer, Ferring, Merck, Mithra, Mylan, Myovant Sciences, Organon. They have been a consultant for AbbVie and Myovant Sciences and served on the Speaker Bureau for AbbVie. Served on the advisory board for BCD Meetings & Events (December 10, 2021).Roberta Venturella has been a consultant for IBSA Pharmaceuticals and Myovant Sciences Inc. Elizabeth Stewart has been a consultant for AbbVie, Bayer, Myovant Sciences, and ObsEva. She received Research Support from the National Institutes of Health (R01 HD105714) and AHRQ and PCORI (P50 HS023418). She holds a patent for Methods and Compounds for Treatment of Abnormal Uterine Bleeding (US 6440445), which has no commercial activity. She has received royalties from UpToDate and payments for the development of educational content from the Med Learning Group, PER, Massachusetts Medical Society, and Peer View. Laura McKain is a former Myovant Sciences, Inc. employee. She served on the speaker's bureau and recently as consultant. She received payment from Evofem Biosciences (consultant role) and Cooper Surgical (consultant role). She is a Myovant Sciences shareholder. Rachel Wagman and Li are current employees of Myovant Sciences, Inc. Alfred Poindexter and Claudio Vil arroel did not report any potential conflicts of interest. (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Al-Hendy, A., et al. (2023). "A plain language summary of the long-term relugolix combination therapy study for uterine fibroids." Journal of comparative effectiveness research 12(8): e230069.
	What is this summary about? This is a summary of a research study (known as a clinical trial) called the LIBERTY extension study. The LIBERTY extension study is a long-term study looking at how well a medicine called relugolix combination therapy worked in reducing blood loss during menstrual periods in women with uterine fibroids with heavy menstrual periods. Women were included in the extension study if they finished the 24-week LIBERTY 1 or LIBERTY 2 studies. Heavy menstrual periods were considered to be menstrual blood loss of about one-third of a cup of blood (80 ml) per cycle for two cycles or about two-thirds of a cup of blood (160 ml) during one cycle. The LIBERTY extension study also looked at whether relugolix combination therapy was safe to take for up to 1 year. What were the results? Out of 770 total women with uterine fibroids with heavy menstrual bleeding who took part in the LIBERTY 1 and LIBERTY 2 studies, 476 took part in the LIBERTY extension study. From the start of the LIBERTY 1 and LIBERTY 2 studies through the end of the LIBERTY extension: 163 women took relugolix combination therapy for 52 weeks 149 women took relugolix alone for 12 weeks followed by relugolix combination therapy for 40 weeks 164 women took placebo for 24 weeks followed by relugolix combination therapy for 28 weeks The LIBERTY extension study showed that most women in all three treatment groups responded to relugolix combination therapy by having less bleeding during their menstrual periods, having improved anemia symptoms, and having stable bone mineral loss. Side effects were similar across treatment groups, and the most common side effects were headaches and hot flushes. What do the results mean? Women with uterine fibroids with heavy menstrual bleeding taking relugolix combination therapy may have fewer uterine fibroid bleeding symptoms for up to 1 year of treatment. Clinical Trial Registration: NCT03049735 (ClinicalTrials.gov) (LIBERTY 1) Clinical Trial Registration: NCT03103087 (ClinicalTrials.gov) (LIBERTY 2) Clinical Trial Registration: NCT03412890 (ClinicalTrials.gov) (LIBERTY extension study).

Al-Hendy, A., et al. (2024). "Fibroids and unexplained infertility treatment with epigallocatechin gallate: A natural compound in green tea (FRIEND) - Protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids." BMJ Open 14(1): e078989.
	Introduction Uterine fibroids affect 30%-77% of reproductive-age women and are a significant cause of infertility. Surgical myomectomies can restore fertility, but they often have limited and temporary benefits, with postoperative complications such as adhesions negatively impacting fertility. Existing medical therapies, such as oral contraceptives, gonadotropin hormone-releasing hormone (GnRH) analogues and GnRH antagonists, can manage fibroid symptoms but are not fertility friendly. This study addresses the pressing need for non-hormonal, non-surgical treatment options for women with fibroids desiring pregnancy. Previous preclinical and clinical studies have shown that epigallocatechin gallate (EGCG) effectively reduces uterine fibroid size. We hypothesise that EGCG from green tea extract will shrink fibroids, enhance endometrial quality and increase pregnancy likelihood. To investigate this hypothesis, we initiated a National Institute of Child Health and Human Development Confirm-funded trial to assess EGCG's efficacy in treating women with fibroids and unexplained infertility. Methods and analysis This multicentre, prospective, interventional, randomised, double-blinded clinical trial aims to enrol 200 participants with fibroids and unexplained infertility undergoing intrauterine insemination (IUI). Participants will be randomly assigned in a 3:1 ratio to two groups: green tea extract (1650 mg daily) or a matched placebo, combined with clomiphene citrate-induced ovarian stimulation and timed IUI for up to four cycles. EGCG constitutes approximately 45% of the green tea extract. The primary outcome is the cumulative live birth rate, with secondary outcomes including conception rate, time to conception, miscarriage rate, change in fibroid volume and symptom severity scores and health-related quality of life questionnaire scores. Ethics and dissemination The FRIEND trial received approval from the Food and Drug adminstration (FDA) (investigational new drug number 150951), the central Institutional Review Board (IRB) at Johns Hopkins University and FRIEND-collaborative site local IRBs. The data will be disseminated at major conferences, published in peer-reviewed journals and support a large-scale clinical trial. Trial registration number NCT05364008.Copyright © 2024 Author(s). Published by BMJ.

Al-Hendy, A., et al. (2022). "Incidence of Alopecia in Treatment of Women With Uterine Fibroids: Results of Two Phase 3 Trials of Linzagolix." Obstetrics and Gynecology 139(SUPPL 1): 30S.
	INTRODUCTION: Although hair loss (alopecia) is a benign disorder, it can negatively affect patient's self-esteem, self-image, and overall quality of life. Linzagolix is an oral GnRH antagonist being developed at full and partial suppression doses with and without hormonal addback therapy (ABT) for treatment of uterine fibroid-related symptoms. Alopecia was previously reported with other GnRH antagonists. METHOD(S): PRIMROSE 1 and 2 are two randomized, double-blind, placebo-controlled phase 3 trials investigating the efficacy and safety of linzagolix 100 mg and 200 mg once daily, +/- ABT in the treatment of uterine fibroids for 52 weeks. RESULT(S): Up to week 24, alopecia was reported in total of five subjects (0.5%) in the pooled safety analysis set (N=1037). There was a similar incidence in the placebo (two subjects; 1.0%), 100 mg (one subject; 0.5%), and 200 mg+ABT groups (two subjects; 1.0%), and no reports in the 100 mg+ABT or 200 mg groups. Four of the cases resolved. For one subject (200 mg+ABT group) mild alopecia had not resolved. For this subject, the study drug was continued, and no concomitant therapy was administered for the alopecia. Up to week 52, one (0.1%) subject in the 200 mg+ABT group reported alopecia, which resolved. None of the cases led to treatment discontinuation. No subjects reported alopecia during the post-treatment follow-up. CONCLUSION(S): Hair loss (alopecia) was rarely observed in the PRIMROSE trials of linzagolix in the treatment of uterine fibroids.

Al-Hendy, A., et al. (2021). "LIBERTY RANDOMIZED WITHDRAWAL STUDY: 2-YEAR EFFICACY AND SAFETY OF RELUGOLIX COMBINATION THERAPY IN WOMEN WITH HEAVY MENSTRUAL BLEEDING ASSOCIATED WITH UTERINE FIBROIDS." Fertility and Sterility 116(3): e2.
	Objective: In the pivotal LIBERTY 1 and 2 trials and Long‐Term Extension (LTE) study, once‐daily relugolix combination therapy (Rel‐CT: relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) reduced menstrual blood loss (MBL) volume and pain in women with uterine fibroids (UF). Rel‐CT was well tolerated, with preservation of bone mineral density (BMD) through 52 weeks. Here we report results of the Phase 3 LIBERTY randomized withdrawal study (RWS), designed to evaluate the efficacy and safety of Rel‐CT for up to 2 years. Materials and Methods: Women with UF‐associated heavy menstrual bleeding (HMB) who completed the 24‐week LIBERTY 1 or 2 trials and the 28‐week LTE study, and who met responder criteria (MBL <80 mL and ≥50% reduction from pivotal study baseline at Week 48 in the LTE study) were randomized 1:1 to blinded treatment with Rel‐CT or placebo for up to 52 weeks (total treatment period: 104 weeks). For women who had a relapse of HMB during the study (MBL volume ≥80 mL), treatment with open‐label Rel‐CT was provided. Primary endpoint was the proportion of women who maintained MBL volume <80 mL at Week 76. Key secondary endpoints included time to MBL volume ≥80 mL, proportion of women who maintained a MBL volume of <80 mL through Week 104 (over the 52‐week randomized treatment period), and the proportion of women achieving or maintaining amenorrhea at Week 76/end of treatment. Results: Of the 229 randomized women (Rel‐CT: 115, placebo: 114), 228 were treated and 89 (77.4%) and 86 (75.4%) completed the RWS. At Week 76, 78.4% of women on Rel‐CT maintained MBL <80 mL vs 15.1% in the placebo group (p<0.0001). Through Week 104, 88.3% of women randomized to placebo at Week 52 relapsed with HMB, with a median time to relapse of 5.9 weeks. Among the 89 women in the placebo group who relapsed and received open‐label rescue treatment, 87 women responded to Rel‐CT, with an MBL <80 mL. At Week 104, 69.8% of women on Rel‐CT maintained MBL <80 mL vs 11.8% in the placebo group (p<0.0001). The proportion of women who achieved or maintained amenorrhea was 57.4% vs 13.3% at Week 76 and 58.3% vs 10.6% at Week 104 for Rel‐CT vs the placebo group, respectively (both p<0.0001). Rel‐CT was generally well tolerated; no new safety signals were detected, and the adverse event profile was consistent with that reported through 1 year of treatment. BMD remained stable in women who received Rel‐CT from Week 52 to Week 104, and cumulative assessment showed that BMD was maintained through 2 years of treatment. Conclusions: After 2 years of treatment with Rel‐CT, there was evidence of durability of effect in maintaining low MBL volume in women with symptomatic UF. There was evidence of return of HMB in most women after treatment cessation, which improved upon re‐treatment with Rel‐CT. Impact Statement: Long‐term treatment with Rel‐CT was efficacious and generally well tolerated in women with UF.

Al-Hendy, A., et al. (2023). "Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial." F&S science 4(4): 317-326.
	Objective: Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids.; Design: Randomized, double-blind, placebo-controlled, multicenter phase 3 study.; Setting: Hospitals and medical centers.; Patient(s): Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle.; Intervention(s): Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.; Main Outcome Measure(s): Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.; Result(s): Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.; Conclusion(s): Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.; Clinical Trial Registration Number: NCT03400943 (ClinicalTrials.gov).; Competing Interests: Declaration of interest A.A-H. reports funding from National Institutes of Health; consulting fees from AbbVie, Bayer, ObsEva, and Myovant Sciences; and a patent for novel diagnostics and therapeutics for uterine sarcoma (US Patent No. 9,790,562 B2) outside the submitted work. Y.F.Z. has nothing to report. E.G-W., S.P., and C.S. are employees of Bayer AG; T.F. is a former employee of Bayer AG. K.L. is an employee of Bayer Nordic SE. (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Alhusen, J. L., et al. (2021). "A pilot study of a group-based perinatal depression intervention on reducing depressive symptoms and improving maternal-fetal attachment and maternal sensitivity." Archives of Women's Mental Health 24(1): 145-154.
	To conduct a pilot study of a group-based perinatal depression intervention, the Mothers and Babies Course, on depressive symptomatology, maternal-fetal attachment, and maternal sensitivity, 60 pregnant women with moderate to severe depressive symptomatology were randomized to a 6-week intervention or usual care group at their initial prenatal care visit. Measures of depressive symptomatology and maternal-fetal attachment were collected at baseline and 36 weeks gestation. At 12 weeks postpartum, participants completed a measure of depressive symptomatology, and an objective measure of maternal sensitivity was collected. Participants randomized to the intervention group completed an average of 5.2 sessions, and 70% of women completed all six sessions. Exploratory analyses showed that at 12 weeks postpartum, participants randomized to the intervention group had an 8.32-point decrease from baseline on the Edinburgh Postnatal Depression Scale (EPDS) as compared to a 4.59-point decrease among participants randomized to usual care. Participants randomized to the intervention group had a mean change score of 12.60 in maternal-fetal attachment via the Maternal Fetal Attachment Scale (MFAS) as compared to 4.60 among participants in usual care. Maternal sensitivity scores, assessed via the Nursing Child Assessment Satellite Training-Feeding Scale (NCAST-Feeding), were higher at 12 weeks postpartum for women in the intervention group as compared to women in usual care (59.2 and 51.8, respectively). Our pilot study findings provide preliminary support for the benefits of a perinatal depression intervention, delivered in a group setting, on reducing depressive symptomatology, and improving maternal-fetal attachment and maternal sensitivity. Further research, conducted with larger samples, is necessary to determine the effect of this intervention on indicators of maternal attachment.

Ali, A., et al. (2021). "Complications and Efficacy of Uterine Preserving Surgeries for the Repair of Pelvic Organ Prolapse versus Procedures Including Hysterectomy, A Systematic Review."
	
Ali, A., et al. (2023). "The Utilization of Bee Products as a Holistic Approach to Managing Polycystic Ovarian Syndrome-Related Infertility." Nutrients 15(5).
	Bee products, including honey, have been utilized since ancient times for nutritional and therapeutic purposes. Recently, other bee products such as bee pollen, royal jelly, and propolis have caught a lot of attention. Being high in antioxidants and bioactive compounds, these products have established their applications in the pharmaceutical field as supplementary or alternative medicines. This review focuses on their use against polycystic ovarian syndrome (PCOS)-related infertility. A systematic search of electronic databases including PubMed, Web of Science ScienceDirect, and Google Scholar was conducted from their inceptions up to November 2022. Studies with a small sample size, studies with inconclusive data, and pre-prints have been excluded. A narrative synthesis was performed during draft preparation after the authors independently performed a literature search. A total of 47 studies were finalized for the review. It can be observed that in vivo data on the use of bee products in treating PCOS mostly deals with their use in synergism with the PCOS medicines to enhance their effect and/or curb their side effects; however, clinical trials for the same are limited. With the amount of data being limited, it is difficult to map out the mechanism by which these products act in managing PCOS inside the human body. The review gives detailed insights into the reversal and restorative properties of bee products against the aberrations in reproductive health caused by PCOS.

Ali, E., et al. (2023). "Single-incision needleless mini-sling technique for female stress urinary incontinence: A comparative study with standard transobturator inside-out technique." Archivio Italiano di Urologia e Andrologia 95(2): 78-84.
	To evaluate the safety and efficacy of surgeon-tailored polypropylene mesh (STM) through a needle-less single incision mini-slings (SIMS) vs. standard trans-obturator tape (TOT) in the treatment of female stress urinary incontinence (SUI). Method(s): We conducted an open-label randomized controlled trial that included women with SUI. Eligible women were randomized in a 1:1 ratio to receive either standard TOT or SIMS techniques. All procedures were performed using a surgeon-tailored polypropylene mesh and monofilament tape. Result(s): A total of 60 women were included. The mean operative time was significantly longer in the standard TOT group. The mean bleeding rate was significantly higher in the standard TOT group (87.6 +/- 10.6 cc) compared to the SIMS group (60.0 +/- 8.1 cc). There was no urethral injury in both groups. Transient thigh pain occurs in 12 cases (40 %) of the standard TOT and no cases in the SIMS group (p < 0.001). After three months, there was no significant statistical difference between the result of the two groups as regard to cure or improvement rate. No failed cases were reported in both groups (p = 0.64). Likewise, there was no significant difference between the two groups regarding patients' satisfaction rate. Conclusion(s): SIMS was not inferior to standard TOT. STM SIMS is a mini-invasive, relatively safe, reproducible, easy to perform in a short time, with excellent patient tolerability and minimal pain, allowing early return to work and economically effective surgical procedure for the treatment of female stress urinary incontinence.Copyright © 2023 Edizioni Scripta Manent s.n.c.. All rights reserved.

Ali, H. M. H. H., et al. (2022). "Unilateral versus Bilateral Femoral Arterial Access for Uterine Artery Embolization." Open Access Macedonian Journal of Medical Sciences 10: 1432-1439.
	BACKGROUND: Uterine fibroids are the most common benign tumors in women. Their clinical presentation includes menorrhagia, metrorrhagia, lower abdominal pain, and infertility. Treatment of uterine fibroids includes medical management, surgical resection known as myomectomy, as well as minimally invasive options like uterine artery embolization. Uterine artery embolization can be done through unilateral or bilateral femoral arterial access. AIM: We aim to define the differences between unilateral and bilateral femoral access in concern to radiation dose, procedure time, fluoroscopy time, as well as the number of angiographic images. METHOD(S): A total of 48 patients were divided into two groups equally; one with a unilateral femoral access and the other group with a bilateral femoral arterial access. RESULT(S): The age of the patients ranged between 25 and 40 years, embolization was done with calibrated spheres. Bilateral procedures compared to the unilateral ones had less fluoroscopy times (8.6 min vs. 24.3 min), less total procedure time (28.4 min vs. 54.4 min), and less dose area product (155 Gy cm2 vs. 340.5 Gy cm2) as well as less mean number of angiographic images (93.8 vs. 176.5) with no significant difference in puncture site complications. CONCLUSION(S): Fluoroscopy times, procedure times, number of angiographic images, as well as radiation dose were significantly lower in the bilateral approach with no significant difference in the rates of puncture site complications between the two approaches.Copyright © 2022 Hossam Mohsen Hassan Hussein Ali, Sameh Mohamed Abdel-Wahab, Amr Mahmoud Abdel-Samad, Ahmed El-Shimy.

Ali, H. T. O., et al. (2022). "Urinary Complications among Women with Cystoceles: A Systematic Review." International Journal of Pharmaceutical Research and Allied Sciences 11(1): 121-128.
	Cystoceles result from a pelvic-floor support system that is not strong enough. This systematic review aims to study the urinary complications in women with cystoceles, especially SUI, and the complication following surgical repair. PubMed, Web of Science, Science Direct, EBSCO, and Scopus were searched. Study articles were screened by title and abstract using Rayyan QCRI then a full-text assessment was implemented. Thirteen studies were included, with a total of 1043 women with cystoceles and urinary complications. The follow-up duration ranged from 1.4 months to 53 months. Most of the included studies had SUI as a complication of cystoceles. The other complication included urge incontinence, mixed incontinence, frequency, incomplete voiding, and voiding difficulties. Incontinence recurrence and voiding dysfunction were reported only in one investigation. The majority of cystoceles cases had SUI. Frequency, incomplete voiding, urge incontinence, mixed incontinence, and voiding issues were among the other complications. The most frequent surgical complications were pyelonephritis, cystitis, and UTIs.Copyright © 2022 International Journal of Pharmaceutical Research and Allied Sciences. All rights reserved.

Ali, I., et al. (2022). "Effect of Benson's relaxation therapy alone or combined with aerobic exercise on cortisol, sleeping quality, estrogen, and severity of dyspeptic symptoms in perimenopausal women with functional dyspepsia." European Review for Medical and Pharmacological Sciences 26(22): 8342-8350.
	Objective: Besides repeated stress exposure, a sedentary lifestyle and low estrogen levels are risk factors for the development of functional dyspepsia (FD). The aim of this study was to find out the effect of adding aerobic exercise (5 sessions per week) to the daily application of a 40-minute Benson's relaxation therapy (BRT) (diaphragmatic breathing and progressive muscle relaxation applied for 20 minutes in the morning and evening) on Glasgow dyspepsia severity score (GDSS), cortisol, visual analogue scale (VAS) (for abdominal symptoms), estradiol (one of the endogenous estrogens), Pittsburgh sleep quality index (PSQI), and 42-item depression, anxiety, and stress scales (DASS-42) in 60 perimenopausal women with FD.; Patients and Methods: Women who consumed a daily dose of pantoprazole (40 mg tablet administered as a proton pump inhibitor drug) were randomly assigned to an 8-week study group (this group received aerobic exercise plus BRT, N=30) or an 8-week control group (this group received BRT only, N=30).; Results: Significant improvements were reported in all measured variables within women groups (except estradiol of the control group). Compared to the control group, the reported within-group significant improvements in GDSS, cortisol, VAS, PSQI, and DASS-42 were higher in the study group.; Conclusions: Significant improvements in GDSS, cortisol, VAS, PSQI, and DASS-42 could be achieved after adding adjunctive therapies - aerobic exercise and BRT - to the medications of FD in perimenopausal women. Compared to BRT alone, physical exercise plus BRT significantly increases the levels of estradiol in perimenopausal women with FD.

Ali, M., et al. (2021). "Safety and efficacy of elagolix (with and without add-back therapy) for the treatment of heavy menstrual bleeding associated with uterine leiomyomas: a systematic review and meta-analysis." Middle East Fertility Society Journal 26(1): 20.
	Background: Heavy menstrual bleeding (HMB) is a common clinical finding in patients with uterine leiomyomas that can negatively impact their quality of life. Recently, a novel oral GnRH-antagonist (elagolix) has emerged as a possible therapeutic agent for this ailment. Herein data was pooled from clinical trials assessing the safety and efficacy of elagolix with and without add-back therapy. Main text: PubMed and Cochrane library were systematically searched for RCTs that measured the efficacy and safety of elagolix for the treatment of uterine fibroid-associated HMB. All safety and efficacy endpoints were compared between elagolix-alone, elagolix w/add-back therapy, and placebo. The primary efficacy endpoint was defined as the number of women who achieved menstrual blood loss (MBL) < 80 ml and a reduction in MBL from baseline of > 50% at the end of treatment. Secondary outcomes assessed included change in hemoglobin levels, incidence suppression of bleeding and amenorrhea, and the incidence of adverse events. The random effects model was used to pool data, and heterogeneity was assessed using I2. Our search identified 4 clinical trials meeting our PICO criteria, with a total of 916 patients. Analysis of the primary outcome revealed that elagolix-alone was the most effective treatment compared to both placebo (LOR = 3.47, CI = 3.03-3.91, p = 0.000, I2 = 0.0%) and add-back therapy (LOR = 0.64, CI = 0.12-1.16, p = 0.016, I2 = 43.1%). Furthermore, both elagolix groups (irrespective of add-back therapy) observed a significant improvement in post-treatment hemoglobin levels as compared to the placebo group (elagolix-alone vs PBO: LOR = 1.44, CI = 0.66-2.22, I2 = 66.0%, p = 0.000; elagolix-w/add-back therapy vs PBO: LOR = 1.22, CI = 0.78-1.66, I2 = 0.0%, p = 0.000). Concerning safety, while elagolix without add-back therapy had the highest overall incidence of adverse effects (elagolix-alone vs placebo LOR = 0.84, CI = 0.48-1.20, I2 = 7.8%, p = 0.000; elagolix-alone vs elagolix-w/add-back LOR = 0.68, CI = 0.09-1.26, p = 0.024, I2 = 64.6%), the incidence of serious (life threatening) adverse events between all 3 treatment groups was not statistically different. The inclusion of add-back therapy with elagolix made the treatment noticeably safer (elagolix-w/add-back vs placebo: LOR = 0.19, CI = - 0.10 to 0.48, I2 = 0.0%, p = 0.194) without seriously compromising its efficacy. Conclusion(s): High-quality evidence from 4 trials suggests that elagolix is an effective treatment for leiomyoma-associated HMB, with a marked improvement in all efficacy endpoints. Furthermore, the inclusion of add-back therapy in the treatment regimen should be considered as it mitigates the hypoestrogenic effects of elagolix.Copyright © 2021, The Author(s).

Ali, S., et al. (2021). "Cytokine imbalance at materno-embryonic interface as a potential immune mechanism for recurrent pregnancy loss." International immunopharmacology 90: 107118.
	Recurrent pregnancy loss (RPL) is a prominent reproductive disease that distresses about 2%-5% of couples. RPL is the loss of two or more successive spontaneous pregnancies prior to the 20th week of embryo development. The commencement of pregnancy necessitates implantation of the embryo into responsive maternal decidua synchronized with the process of placentation, decidual and myometrial trophoblast incursion as well as refashioning of spiral blood arteries of uterus. The collapse of any of the processes fundamental for pregnancy success may result into an array of pregnancy problems including spontaneous pregnancy loss. Endometrium of human female manufactures an extensive range of cytokines during the proliferative and secretory stage of the menstrual cycle. These endometrial cytokines are thought as major players for making the uterus ready for embryo implantation and placental development during pregnancy. Decidual cytokines regulate the invasion of trophoblast and remodeling of spiral arteries as well as take part in immune suppression to accomplish the pregnancy. Deterrence of maternal rejection of embryo needs a regulated milieu, which takes place essentially at the embryo-maternal interface and the tissues of the uterus. The reasons of RPL remain anonymous in a large number of cases that lead to difficulties in management and severe trauma in couples. Cytokine modulatory therapies have been shown promising for preventing RPL. Further study of novel factors is wanted to establish more effective RPL treatment protocols. The present study aims to review the outcome of cytokine breach at materno-embryonic interface and the efficacy of cytokine modulatory therapies in RPL. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ali, S., et al. (2022). "The effect of antioxidant supplementation on endometriosis-related pelvic pain, a systematic review, and meta-analysis of clinical trials."
	
Aliakbari, F., et al. (2022). "Effects of Combination Therapy with Bunium persicum and Foeniculum vulgare Extracts on Patients with Polycystic Ovary Syndrome." Advanced biomedical research 11: 74.
	Background: Considering the side effects of common drugs used to treat polycystic ovary syndrome (PCOS), researchers have turned their attention to natural compounds, including medicinal plants. Foeniculum vulgare has estrogenic properties and has been traditionally used to treat gynecological disorders. Bunium persicum has medical aspects that have not yet been evaluated, so the aim of this study was to evaluate the effects of combination therapy with these extracts on clinical symptoms of women with PCOS.; Materials and Methods: In this double-blind clinical trial study, 70 women with PCOS referred to infertility clinics, were selected and randomly divided into two groups. The intervention group received B. persicum capsule 60 mg plus F. vulgare capsule 25 mg) twice daily for 4 months and the control groups received routine intervention. Before and after the intervention, levels of luteinizing hormone (LH), follicle-stimulating hormone, progesterone, prolactin, testosterone and dehydroepiandrosterone sulfate (DHEAS) levels, hirsutism score, and menstrual pattern were recorded and endometrial thickness and follicle count were determined by ultrasound. Data were analyzed by the SPSS21 software.; Results: Treatment with B. persicum and F. vulgare extracts significantly decreased LH and DHEAS levels, hirsutism score, and significantly increased menstrual duration compared to the control group. Before the intervention, 5.7% of the intervention and control groups had the normal menstrual pattern, while after the intervention 31.4% of the intervention group and 25.7% of the control group had the normal pattern.; Conclusion: Regarding the effect of these extracts combination and because they have no side-effects, which is a great advantage over chemical drugs, using of these plants recommend.; Competing Interests: There are no conflicts of interest. (Copyright: © 2022 Advanced Biomedical Research.)

Alibhai, K., et al. (2022). "The impact of bariatric surgery on assisted reproductive technology outcomes: a systematic review protocol." Systematic Reviews 11(1): 1.
	BACKGROUND: Individuals with obesity are at higher risk of experiencing complications during their pregnancy and may also experience infertility, requiring assisted reproductive technologies (ART) to conceive. The current body of literature demonstrates that bariatric surgery decreases an individual's risk of developing a variety of obesity-related obstetrical conditions during and after pregnancy. However, the effects of bariatric surgery on ART outcomes are not well understood. Therefore, the paucity in the literature warrants a need to determine these effects. METHODS: We will search electronic databases, including MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), as well as the gray literature and the reference lists of included articles. We will screen all studies published between January 1978 and the present day that explore the impact of bariatric surgery on ART outcomes for women and men. We will include observational studies. Two independent reviewers will assess the studies for inclusion and extract data for each article. The main outcome that will be analyzed is live birth rate. Secondary outcomes such as time to conception, number of rounds of ART, type of bariatric surgery, and length of time between bariatric surgery and initiation of ART will also be recorded. Risk of bias will be conducted using the National Institutes of Health Study Quality Assessment Tools. A random effects model will be used to account for statistical analysis and results will be pooled with forest plots. In the event of statistical and reporting heterogeneity, we will provide a qualitative synthesis and narrative review of the results. DISCUSSION: This review will provide information on the outcomes of ART following bariatric surgery and may help healthcare professionals make informed decisions about the length of time between bariatric surgery and initiation of ART. The study findings may be of interest to various stakeholders including patients, bariatric surgeons, obstetricians, and gynecologists, and those who specialize in obesity medicine and reproductive endocrinology and infertility. We plan to disseminate our findings through presentations, publications, and social media releases to individuals who are navigating infertility and are interested in undergoing or have undergone bariatric surgery, healthcare professionals, policymakers, and researchers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021252561.

Alikamali, M., et al. (2022). "The effects of vitamin E on the intensity of primary dysmenorrhea: A systematic review and meta-analysis." Clinical Nutrition ESPEN 52: 50-59.
	Background & Aims: Primary dysmenorrhea (PD) refers to the presence of painful menstrual cramps due to increased synthesis of prostaglandins. Vitamin E inhibits the release of arachidonic acid and its conversion to prostaglandins through its antioxidant properties. This study sought to examine the effects of oral vitamin E supplementation on PD intensity (primary outcome) and its side effects (secondary outcomes).; Methods: In this systematic review and meta-analysis, databases in English and Persian, including PubMed, Cochrane Library, Google Scholar, Scopus, Web of Science, SID, and Magiran, were systematically searched until August 30, 2021. The study included all randomized, controlled clinical trials comparing oral vitamin E to placebo in healthy women with PD and measuring PD severity as a primary or secondary outcome. The quality of the included articles was assessed using the Cochrane Handbook, and the meta-analysis was performed using RevMan software. Given the continuous nature of the data and the utilization of different tools in the extracted articles, the meta-analysis results were reported using standardized mean difference (SDM) and 95% confidence interval (95% CI). A subgroup analysis was performed in low-dose (100 units), moderate-dose (200 units), and high-dose (400 units) categories. The quality of evidence was examined according to the GRADE approach.; Results: Eight articles with a sample size of 1002 people were entered into this systematic review. The results of meta-analysis revealed that vitamin E consumption significantly reduced PD mean intensity in the first month (n = 7 records; SDM = -1.16; 95%CI: -2.16 to -0.17; I 2 = 31.9%; P = 0.02) and the second month (n = 8 records; SDM = -1.83; 95%CI: -2.90 to -0.77; I 2 = 76.3.9%; P < 0.0001) compared with placebo. Serious side effects were not reported in vitamin E recipients.; Conclusion: Vitamin E could be an adjunctive treatment for women with PD. However, higher-quality clinical trials with larger sample sizes are recommended for a more definite conclusion.; Prospero Id: CRD42021276609.; Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Alimoradi, Z., et al. (2023). "Therapeutic applications of lemon balm (Melissa officinalis) for obstetrics and gynecological health issues: A systematic review." Journal of Herbal Medicine 42: 100751.
	Introduction: Melissa officinalis (lemon balm) is a medicinal herb with several proposed therapeutic uses. The present paper systematically reviewed relevant evidence regarding the applications of M. officinalis for obstetrics and gynecological health issues. Method(s): Utilizing a systematic approach, academic electronic databases including PubMed, Scopus, ProQuest, Web of Science, and the Cochrane Library were searched up to September 21, 2022. The Cochrane Risk of Bias Assessment Toolkit was used to assess the methodological quality of the included studies. Due to methodological heterogeneity among a small number of retrieved studies, evidence was pooled utilizing a narrative synthesis. Result(s): In total, 15 studies were included. M. officinalis appears to be useful in pain reduction (childbirth after pain and primary dysmenorrhea), improving premenstrual symptoms, and postpartum blues. However, no effect was seen on the intensity of menstrual bleeding, and effectiveness was mixed in relation to sexual functioning and menopausal-related symptoms. Due to selection bias in almost all studies, the evidence level of the included studies was considered a high risk of bias. In most studies, no side effects were reported among the intervention groups. When reported they were minor (eg, diarrhea, constipation, flatulence, stomach pain, and sleep disturbance). Discussion/Conclusions: This intervention might have benefits for gynecological conditions but it is not strongly supported by the available evidence. Consequently, further studies are needed with (1) larger sample sizes, (2) more rigorous methodologies using Melissa officinalis alone to avoid synergistic or antagonistic effects, (3) adjustment for potential covariates, (4) toxicity assessment to establish optimal doses, and (5) the most effective forms of preparation.Copyright © 2023 Elsevier GmbH

Alirezaei, S., et al. (2022). "The effect of infertility counseling interventions on marital and sexual satisfaction of infertile couples: A systematic review and meta-analysis." International Journal of Reproductive Biomedicine 20(10): 795-806.
	BACKGROUND: Psychological consequences of infertility could have a negative effect on marital and sexual satisfaction. Numerous medical associations have strongly recommended psychological interventions, including counseling, to help infertile couples. OBJECTIVE: This study reviewed the effectiveness of counseling interventions on marital and sexual satisfaction in infertile couples. MATERIALS AND METHODS: This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist Databases including PubMed, Web of Science, Psych Info, Cochran Library, Scopus, and Embase were searched for relevant articles published up to March 2020. All randomized clinical trials assessing the impact of psychological interventions on marital and sexual satisfaction in infertile couples were included in the review. The outcome measures were marital and sexual satisfaction, and the pooled estimate of the effects was calculated using a random-effects model. The risk of bias was measured using the Cochrane risk of bias tool, and the summary measures were reported as 95% confidence interval and percentage of heterogeneity. RESULTS: Out of the 309 studies found through the search, 13 randomized clinical trials including 230 infertile women and 512 infertile couples were systematically reviewed and included in the meta-analysis. It was found that counseling interventions improve marital and sexual satisfaction. CONCLUSION: As counseling and psychological interventions increase the marital and sexual satisfaction of infertile couples, those are highly recommended for the psychological management of infertile couples.

Alkatout, I., et al. (2023). "Total or Subtotal Hysterectomy for the Treatment of Endometriosis: A Review." Journal of Clinical Medicine 12(11).
	Objective: The purpose of the review was to evaluate and compare outcomes after total or subtotal hysterectomy in women with endometriosis or adenomyosis.; Methods: We searched four electronic databases: Medline (PubMed), Scopus, Embase, and Web of Science (WoS). The first aim of the study was to compare outcomes after total and subtotal hysterectomy in women with endometriosis, and the second aim was to compare the two procedures in women with adenomyosis. Publications that reported short- and long-term outcomes after total and subtotal hysterectomy were included in the review. The search was not subject to any limitation in terms of time or method.; Results: After screening 4948 records, we included 35 studies published from 1988 to 2021; the studies were based on various methodologies. With regard to the first aim of the review, we found 32 eligible studies and divided these into the following four categories: postoperative short- and long-term outcomes, recurrence of endometriosis, quality of life and sexual function, and patient satisfaction after total or subtotal hysterectomy in women with endometriosis. Five investigations were deemed eligible for the second aim of the review. No differences were seen in terms of postoperative short- and long-term outcomes after subtotal or total hysterectomy in women with endometriosis or adenomyosis.; Conclusions: Preservation or removal of the cervix in women with endometriosis or adenomyosis appears to have no effect on short- or long-term outcomes, recurrence of endometriosis, quality of life and sexual function, or patient satisfaction. Nevertheless, we lack randomized blinded controlled trials on these aspects. Such trials will be needed to enhance our comprehension of both surgical approaches.

Alkermes, I., et al. (2022). Phase 3 Study of Nemvaleukin Alfa in Combination With Pembrolizumab in Patients With Platinum-Resistant Epithelial Ovarian Cancer (ARTISTRY-7).
	No Results Available Biological: Nemvaleukin and Pembrolizumab Combination|Biological: Pembrolizumab|Biological: Nemvaleukin|Drug: Pegylated Liposomal Doxorubicin (PLD)|Drug: Paclitaxel|Drug: Topotecan|Drug: Gemcitabine Progression-free survival (PFS) as assessed by Investigator|Objective response rate as assessed by Investigator|Overall Survival Rate|Disease Control Rate (DCR) as assessed by Investigator|Duration of Response (DOR) as assessed by Investigator|Time to Response (TTR) as assessed by Investigator|Cancer antigen (CA)-125 response as defined by the Gynecologic Cancer InterGroup (GCIG)|Incidence of treatment-emergent adverse events (TEAEs) Female Phase 3 376 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment ALKS 4230-007|GOG-3063|ENGOT-OV68|KEYNOTE-C71 December 2026

Alkis, O., et al. (2022). "How effectively do we apply first-line treatment in overactive bladder?" International Urogynecology Journal 33(8): 2299-2306.
	INTRODUCTION AND HYPOTHESIS: We aimed to reveal the effectiveness of the combination of behavioral therapy (BT), drug therapy, and pelvic floor muscle training (PFMT) in patients with the diagnosis of overactive bladder (OAB) who did not respond to drug therapy. METHODS: Seventy female patients aged between 18 and 65 years diagnosed with wet-type OAB, who did not respond to drug therapy, were included in our study, which was planned as a prospective randomized controlled trial. The patients were randomly assigned to one of two groups. BT and a combination of anticholinergic + beta3-agonist was implemented in the control group for 12 weeks. BT and PFMT were applied with a combination of anticholinergic + beta3-agonist in the active therapy group for 12 weeks. Post-treatment changes in OAB, ICIQ-SF scores, and frequency and nocturia were compared. RESULTS: The age and BMI averages of the groups were similar (p>0.01). After the treatment, no significant decrease was observed in OAB scores in the control group (p = 0.06), but a significant decrease was observed in the active therapy group (p<0.01). The mean ICIQ-SF scores and the number of nocturia were found to decrease in both groups after 12 weeks of treatment (p<0.01). There was no significant decrease in frequency in the control group (p = 0.054). It regressed significantly in the active therapy group (p<0.01). After the treatment, 3 of 30 the patients in control group (10%) and 11 of the 32 patients in the active therapy group (34.3%) said that their complaints had regressed and that they were pleased with their current situation. Although after the treatment, 4 patients in the control group were dry (13.3%), 10 patients in the active therapy group were dry (31.25%). CONCLUSIONS: We demonstrated that drug therapy, BT, and PFMT, which are recommended in the first-line treatment of OAB reduce the need for invasive treatments when they are well explained to the patients and combined.

Allahqoli, L., et al. (2023). "Appendiceal Endometriosis: A Comprehensive Review of the Literature." Diagnostics 13(11): 1827.
	Objective: the purpose of this review was to evaluate the prevalence of appendiceal endometriosis and the safety of concomitant appendectomy in women with endometriosis or pelvic pain. Material(s) and Method(s): We searched the electronic databases Medline (PubMed), Scopus, Embase, and Web of Science (WOS). The search was not subject to any limitation in terms of time or method. The primary research question was: what is the prevalence of appendiceal endometriosis? The secondary research question was: is it safe to perform appendectomy during surgery for endometriosis? Publications that reported data about appendiceal endometriosis or appendectomy in women with endometriosis were reviewed regarding the inclusion criteria. Result(s): We found 1418 records. After review and screening, we included 75 studies published between 1975 and 2021. With regard to the first question of the review, we found 65 eligible studies and divided these into the following two categories: (a) endometriosis of the appendix presenting as acute appendicitis, and (b) endometriosis of the appendix as an incidental finding in gynecological surgery. Forty-four case reports described appendiceal endometriosis in women who were admitted for the treatment of pain in the right-sided lower abdomen. Endometriosis of the appendix was observed in 2.67% (range, 0.36-23%) of women who were admitted due to acute appendicitis. In addition, appendiceal endometriosis was an incidental finding during gynecological surgery in 7.23% of cases (range, 1-44.3%). With regard to the second question of the review, which was the safety of appendectomy in women with endometriosis or pelvic pain, we found 11 eligible studies. Reviewed cases had no significant intraoperative or follow-up complications during the 12 weeks. Conclusion(s): Based on the reviewed studies, coincidental appendectomy appears reasonably safe and was associated with no complications in the cases reviewed for the present report.Copyright © 2023 by the authors.

Allen, L. A., et al. (2022). "Long-term health outcomes in young women with polycystic ovary syndrome: A narrative review." Clinical Endocrinology 97(2): 187-198.
	Polycystic ovary syndrome (PCOS) has long been recognized as a common disorder in young women leading to reproductive and cutaneous sequelae. However, the associated health risks are now known to extend beyond these familiar manifestations to a range of longer-term comorbidities. Here we review the evidence for an association of PCOS with adverse long-term health outcomes, discussing the pathophysiological mechanisms involved in addition to opportunities for therapeutic intervention. Cross-sectional and longitudinal studies point to an increased risk of type 2 diabetes, hypertension and dyslipidaemia, with recent data confirming that these translate to an increased risk of cardiovascular events independently of obesity. Obstructive sleep apnoea, nonalcoholic fatty liver disease and endometrial cancer are also more prevalent, while mental health disorders, notably anxiety and depression, are common but under-appreciated associations. Uncertainties remain as to whether these risks are apparent in all patients with PCOS or are confined to particular subtypes, whether risks persist post-menopausally and how risk may be affected by ethnicity. Further work is also needed in establishing if systematic screening and targeted intervention can lead to improved outcomes. Until such data are available, clinicians managing women with PCOS should counsel patients on long-term health risks and invest in strategies that limit progression to metabolic and non-metabolic morbidities.Copyright © 2021 John Wiley & Sons Ltd.

Allenby, T. H., et al. (2020). "A systematic review of home-based dietary interventions during radiation therapy for cancer." Technical Innovations and Patient Support in Radiation Oncology 16: 10-16.
	Purpose: Our objectives are to assess (1) the acceptability and feasibility of dietary interventions for patients undergoing radiation therapy (RT), and (2) the impact of dietary interventions on patient reported outcomes, toxicities, and survival. Method(s): A PICOS/PRISMA/MOOSE selection protocol was used to include articles that evaluate adding dietary interventions to patients receiving RT. Acceptability was defined as (# accepting/# approached); feasibility was (# completing/# approached). Patient-reported outcomes were reported based on questionnaires used in each study and survival was measured from the date of diagnosis until death in each study. Level of evidence was assessed with Center for Evidence-Based Medicine (CEBM) criteria. Result(s): Sixteen articles were included; among these, 2027 patients were approached regarding the intervention, and 1661 accepted (81.9%); of these, 1543 (92.9%) completed the prescribed diet + RT course. The most common cancers included were gynecological, head and neck, and gastrointestinal. For patients with pelvic cancers, a high fiber diet may improve diarrhea (CEBM level 1b). Enteral nutrition formula, including formulas with proteins such as L-arginine, lipids such as eicosapentaenoic acids, glucids, and ribonucleotides, may help prevent of malnutrition in head and neck cancer patients undergoing RT (level 2b). Vitamin C and beta-carotene may reduce of xerostomia in head and neck cancer patients; however, the studies evaluating these vitamins included vitamin E, which increases all-cause mortality (level 2b). No dietary intervention for cancer patients receiving RT has been shown to improve survival. Conclusion(s): There are limited data to support safe and efficacious use of dietary interventions during RT.Copyright © 2020 The Authors

Alliance Foundation, T., et al. (2021). A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer.
	No Results Available Drug: Atezolizumab - 28 Day Cycle|Drug: Bevacizumab|Drug: Ipatasertib|Drug: Talazoparib|Drug: Trastuzumab emtansine|Drug: Tiragolumab|Drug: Atezolizumab - 21 Day Cycle|Drug: Inavolisib|Drug: Letrozole|Drug: Giredestrant|Drug: Abemaciclib Investigator-assessed overall response rate (ORR) of each biomarker cohort|The proportion of participants in each biomarker cohort who remain alive and progression-free for at least 6 months|Relative proportion of participants in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies|Investigator assessed disease-control rate of each biomarker cohort|Duration of response for participants in each biomarker cohort who achieve a complete or partial response.|Overall survival (OS) rates of participants in each biomarker cohort after 24 months|Duration of response for participants in each biomarker cohort who achieve a confirmed response (complete or partial)|Overall survival rates of participants in each biomarker cohort Female Phase 1|Phase 2 148 Other|Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment AFT-50 October 2026

Almohammadi, A., et al. (2023). "The optimal route of progesterone administration for luteal phase support in a frozen embryo transfer: a systematic review." Archives of Gynecology and Obstetrics 308(2): 341-350.
	Objective: To investigate the optimal route of progesterone administration for luteal phase support in a frozen embryo transfer.; Design: Systematic review.; Patients: Women undergoing frozen embryo transfer (FET).; Interventions: We conducted an extensive database search of Medline (PubMed), Embase, Web of Science, and Cochrane Trials Register using relevant keywords and their combinations to find randomized controlled trials (RCTs) comparing the routes (i.e., oral, vaginal, intramuscular) of progesterone administration for luteal phase support (LPS) in artificial FET.; Main Outcome Measures: Clinical pregnancy, live birth, miscarriage.; Results: Four RCTs with 3245 participants undergoing artificial endometrial preparation (EP) cycles during FET were found to be eligible. Four trials compared vaginal progesterone with intramuscular progesterone and two trials compared vaginal progesterone with oral progesterone. One study favored of vaginal versus oral progesterone for clinical pregnancy rates (RR 0.45, 95% CI 0.22-0.92) and other study favored intramuscular versus vaginal progesterone for clinical pregnancy rates (RR 1.46, 95% CI 1.21-1.76) and live birth rates (RR 1.62, 95% CI 1.28-2.05). Tabulation of overall evidence strength assessment showed low-quality evidence on the basis that for each outcome-comparison pair, there were deficiencies in either directness of outcome measurement or study quality.; Conclusion: There was little consensus and evidence was heterogeneous on the optimal route of administration of progesterone for LPS during FET in artificial EP cycles. This warrants more trials, indirect comparisons, and network meta-analyses.; Propero No: CRD42021251017. (© 2022. The Author(s).)

Almuslim, H. and S. AlDossary (2022). "Models of incorporating telehealth into obstetric care during the COVID-19 pandemic, its benefits and barriers: A scoping review." Telemedicine and e-Health 28(1): 24-38.
	Introduction: Coronavirus disease 2019 (COVID-19) is a highly contagious viral infection. Hospitals worldwide have decreased face-to-face visits to reduce the exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Prenatal and postpartum care are essential for the health of women and their fetuses. Therefore, many hospitals have incorporated telehealth into their protocols. Objectives: The aim of this review was to determine how health care organizations are responding to the COVID-19 pandemic by incorporating telehealth visits into their protocols for obstetrics care, what services were converted to telehealth, and its benefits and barriers. Method: A computerized literature search was performed using PubMed and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases using terms, including "telehealth," "virtual visits," "obstetric," "pregnancy," "postpartum," and "COVID-19" for articles published before October 2020. Peer reviewed articles and guidelines were included in this review. Results: A total of 25 articles were identified. Fifteen articles reported protocols. During this pandemic, protocols developed replaced some in-person visits with telehealth visits, when no testing or vaccinations are required. The main reported benefits were minimizing exposure to SARS-CoV-2 and the continuity to provide high-quality and safe care. Lack of access to high-speed internet and hardware and inaccessibility to patients were the most reported barriers. Conclusion: Telehealth provided the opportunity for reducing in-person visits during the COVID-19 pandemic. Some prenatal services could be completely provided through telehealth and others require medical equipment to be delivered. Health care organizations recognized that using telehealth could be continued beyond this pandemic, as they provided many benefits for patients, medical staff, and the organizations themselves. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Alomar, O., et al. (2022). "Prophylactic vasopressin to reduce intraoperative blood loss and associated morbidities during myomectomy: A systematic review and meta-analysis of 11 controlled trials." Journal of Gynecology Obstetrics and Human Reproduction 51(10): 102485.
	Objective: To collate evidence from randomized controlled trials (RCTs) and nonrandomized controlled trials (NCTs) on the efficacy and safety of vasopressin versus passive control (placebo/no treatment) during myomectomy.; Methods: Six information sources were screened until 25-June-2022. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to evaluate the risk of bias. Data were summarized as mean difference or risk ratio with 95% confidence interval in a random-effects model.; Results: Eleven studies, comprising 1067 patients (vasopressin=567 and control=500) were analyzed. For RCTs (n = 8), the overall quality included 'high risk' (n = 4), 'low risk' (n = 2), and 'some concerns' (n = 2). For NCTs (n = 3), the overall quality included 'good' (n = 2) and 'fair' (n = 1). The mean intraoperative blood loss, mean difference in hemoglobin level, mean difference in hematocrit level, rate of perioperative blood transfusion, and mean operative time were significantly reduced in favor of the vasopressin group compared with the control group. However, there was no significant difference between both groups regarding the mean hospital stay. Pertaining to safety endpoints, after omission of an outlier study, the rate of drug-related cardiovascular adverse events did not significantly differ between both groups. There was no quantitative evidence of publication bias for the endpoint of intraoperative blood loss.; Conclusion: Among patients undergoing myomectomy, prophylactic administration of vasopressin was largely safe and correlated with significant reductions in intraoperative blood loss and associated morbidities compared with a passive control intervention. Nonetheless, the conclusions should be cautiously interpreted owing to the low-evidence quality and the used doses varied greatly between studies.; Competing Interests: Declaration of Competing Interest The authors report no conflict of interest. (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Alomran, S. and E. D. Estrella (2023). "Effect of Dietary Regimen on the Development of Polycystic Ovary Syndrome: A Narrative Review." Cureus 15(10): e47569.
	BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 4%-20% of women worldwide. The pathogenesis of PCOS is still unconfirmed. Some risk factors for the disease are obesity, insulin resistance, genetic factors, and diet. AIM: Our aim is to review studies investigating the role of diet in the development of PCOS. METHOD: We looked into studies published in different databases, such as PubMed, Scopus, Google Scholar, and Web of Science, using specific keywords as per our study topic. RESULTS: High-carbohydrate, high-fat diets, low-fiber diets, high glycemic index and glycemic load, and Western diets were associated with a higher risk of PCOS. Some vitamins, such as Vitamin D and B9, the Dietary Approaches to Stop Hypertension (DASH) diet, fruits, nuts, and seeds, such as pumpkin and sunflower, are associated with a lower risk of PCOS. The Alternate Healthy Eating Index-2010 (AHEI-2010) diet reduces the risk of hyperandrogenic or oligoanovulatory phenotypes. The review revealed that unhealthy diets encompass high levels of carbohydrates, animal proteins, fats, and processed foods. Despite inconsistent results from certain studies claiming no disparity in the dietary patterns between PCOS patients and healthy controls, the majority of researchers have amassed sufficient evidence linking nutrition to the incidence of PCOS. The review also underscores the significance of the interplay between genes and the environment in the prevalence of PCOS. Individuals possess a genetic predisposition to the condition from birth, and subsequent exposure to detrimental environmental factors, particularly diet and inactivity, trigger epigenetic changes that contribute to the development of the disorder. This study further illuminated the existence of the "lean PCOS" phenomenon, wherein roughly 20% of global PCOS cases exhibit clinical manifestations of the syndrome but maintain a normal or below-average weight. CONCLUSION: To sum up, the collective body of assessed research indicates that women with PCOS tend to share similar dietary habits, characterized by the consumption of numerous unhealthy foods such as processed foods, animal proteins, carbohydrates, and fats. While some studies present conflicting findings, these contradictions underscore the necessity for further investigation employing extensive cohorts.

Alonso, D., et al. (2023). "Digestive toxicity in cancer treatments. Bibliographic review. Influence on nutritional status." Endocrinologia, diabetes y nutricion 70(2): 136-150.
	Introduction: The cause of death can be attributed to malnutrition in 10-20% of cancer patients. Patients with sarcopenia present more chemotherapy toxicity, less progression-free time, less functional capacity and more surgical complications. Antineoplastic treatments have a high prevalence of adverse effects that compromise nutritional status. The new chemotherapy agents present direct toxicity on the digestive tract (nausea, vomiting, diarrhoea and/or mucositis). We present the frequency of adverse effects with nutritional impact of the most frequent chemotherapy agents used in the treatment of solid tumours, as well as strategies for early diagnosis and nutritional treatment.; Material and Methods: Review of commonly used cancer treatments (cytotoxic agents, immunotherapy, targeted therapies) in colorectal, liver, pancreatic; lung, melanoma, bladder, ovary, prostate and kidney cancer. The frequency (%) of gastrointestinal effects, and those of grade ≥3 are recorded. A systematic bibliographic search was carried out in PubMed, Embase, UpToDate, international guides and technical data sheets.; Results: They are shown in the form of tables in which the drugs appear together with the probability that they present any digestive adverse effect and the percentage of serious adverse effects (Grade ≥ 3).; Discussion: Antineoplastic drugs are associated with a high frequency of digestive complications with nutritional repercussions, which can reduce QoL and cause death as a result of malnutrition or due to the limiting effect of suboptimal treatments, closing the malnutrition-toxicity loop. It is necessary to inform the patient about the risks and establish local protocols regarding the use of antidiarrheal drugs, antiemetics and adjuvants in the management of mucositis. We propose action algorithms and dietary advice that can be used directly in clinical practice, to prevent the negative consequences of malnutrition. (Copyright © 2023. Published by Elsevier España, S.L.U.)

Alouini, S., et al. (2022). "Pelvic Floor Muscle Training for Urinary Incontinence with or without Biofeedback or Electrostimulation in Women: A Systematic Review." International Journal of Environmental Research and Public Health 19(5).
	To determine the effectiveness of pelvic floor muscle training (PFMT) with or without biofeedback or electrostimulation in reducing urinary incontinence and pelvic floor muscle con-traction in non-pregnant women with urinary incontinence.; Methods: The following electronic databases were searched: PubMed, Cochrane Central, ClinicalTrials.gov, EU Clinical Trials Register, and sources from NICE, FDA, EMA, and SMC (articles only in English, 2000-2021). Search terms were: urinary incontinence, pelvic floor muscle training or exercises, biofeedback, electrostimulation. We used the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) for this systematic review. Relevant articles were selected, data were extracted, and quality was assessed. Data were extracted in predesigned form, followed by narrative synthesis.; Results: Following the search, 15 RCTs were retrieved using the strict inclusion and exclusion criteria, assessing 2441 non-pregnant women with urinary incontinence. Of the 15 studies, 7 were low risk, 5 were medium risk, and 3 were high-risk studies. Of the 2441 patients, 970 were in PFMT, 69 were in extracorporeal magnetic innervation (ExMi) or with PFMT + BF, 30 were in electrostimulation (ES), 21 were in whole body vibration training (WBVT), 23 were in pelvic floor muscle + abdominal muscle therapy (PFM + AMT), 326 were in PFMT + biofeedback, 93 were in vaginal cones (VC), 362 were in PFMT + education, 318 were in education, and 229 were in control groups. The most often measures employed were pad tests, bladder diary, and questionnaire on the quality of life. Stress, urge and mixed urinary incontinence were studied. In all RCT, PFMT significantly reduced urinary incontinence, essentially SIU and MUI, when compared with the control group before and after treatment. Overall, out of 997 PFMT or PFMT + education patients, 504 patients (50.5%) showed improvement in urinary incontinence, and 218 became continent (21.8%) (negative pad test). In total, 62% of patients significantly reduced their urinary incontinence or cured it and improved their pelvic floor muscle contraction. All other physiotherapist techniques also significantly reduced urinary leakages, e.g., vaginal cones, biofeedback, ExMI, and WBVT when compared with the control group. There were no significant differences between these methods in reducing the severity of urinary incontinence.; Conclusion: PFMT alone or with bio-feedback or electrostimulation was effective in reducing urinary incontinence and improving pelvic floor muscle contraction. PFMT when compared with other interventions such as bio-feedback, VC, and WBVT did not show significant differences but was superior to the control group. RCT studies with similar parameters used for measuring the outcomes need to be included.

Alrawashdh, N., et al. (2022). "Meta-Analysis of Same-Day Pegfilgrastim Administration Stratified by Myelotoxic Febrile Neutropenia Risk and Tumor Type." Journal of the advanced practitioner in oncology 13(8): 796-811.
	BACKGROUND: Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. METHODS: Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. CONCLUSION: In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

Alrhmoun, S. and S. Sennikov (2022). "The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions." Cancers 14(24): 6173.
	The treatment of HER2-positive cancers has changed significantly over the past ten years thanks to a significant number of promising new approaches that have been added to our arsenal in the fight against cancer, including monoclonal antibodies, inhibitors of tyrosine kinase, antibody-drug conjugates, vaccination, and particularly, adoptive-T-cell therapy after its great success in hematological malignancies. Equally important is the new methodology for determining patients eligible for targeted HER2 therapy, which has doubled the number of patients who can benefit from these treatments. However, despite the initial enthusiasm, there are still several problems in this field represented by drug resistance and tumor recurrence that require the further development of new more efficient drugs. In this review, we discuss various approaches for targeting the HER2 molecule in cancer treatment, highlighting their benefits and drawbacks, along with the different mechanisms responsible for resistance to HER2-targeted therapies and how to overcome them.Copyright © 2022 by the authors.

Al-Samkari, H., et al. (2022). "Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial." The Lancet. Haematology 9(3): e179-e189.
	Background: Chemotherapy-induced thrombocytopenia is common and causes chemotherapy dose reductions or treatment delays, bleeding, and suboptimal oncological outcomes. We aimed to evaluate avatrombopag, a thrombopoietin receptor agonist that increases platelet counts, in patients with non-haematological cancer and platelet counts lower than 50 ×10 9 cells per L.; Methods: In this randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18 years or older at 71 hospitals or cancer treatment centres in China, Hungary, Poland, Russia, Serbia, Ukraine, and the USA and with ovarian, bladder, or lung cancer receiving chemotherapy who had severe thrombocytopenia were randomly assigned (2:1) to oral avatrombopag 60 mg or oral placebo once daily given 5 days before and after chemotherapy, with randomisation stratified by number of chemotherapy drugs used. Patients, investigators, and data collectors were masked to group allocation. Eligibility required two previous lines of chemotherapy or fewer, an ECOG performance status of 2 or less, and no previous history of chemotherapy-induced thrombocytopenia. The composite primary endpoint was the proportion of responders not requiring platelet transfusion or either a 15% or more chemotherapy dose reduction or a 4-day or more chemotherapy delay due to thrombocytopenia following study treatment until the start of the subsequent cycle. Analyses were done on the intention-to-treat and per protocol populations. Safety was analysed in all patients who received at least one dose of avatrombopag. The trial is registered with ClinicalTrials.gov, NCT03471078, and has been completed.; Findings: Between Oct 12, 2018, and June 28, 2020, 122 patients were enrolled and randomly assigned to receive avatrombopag (n=82) or placebo (n=40). Median follow-up was 31 days (IQR 22-61). Similar proportions of patients reached the primary endpoint in the avatrombopag and placebo groups (intention-to-treat: 57 [70%, 95% CI 58-79] of 82 vs 29 [73%, 95% CI 56-85] of 40; difference -3·0% (95% CI -21·6 to 15·6); p=0·72; per protocol: 51 [85%, 95% CI 73-93] of 60 vs 27 [84%, 95% CI 67-95] of 32; 0·6% (95% CI -20·8 to 22·1); p=0·96). 15 (18%) of 82 patients had serious adverse events in the avatrombopag group and eight (20%) of 40 in the placebo group, of which thrombocytopenia was most common (4 [5%] of 82 and 4 [10%] of 40 patients). Common grade 3-4 treatment-emergent adverse events were neutropenia (22 [27%] of 82 and 16 [40%] of 40 patients), leukopenia (19 [23%] of 82 and 5 [13%] of 40), anaemia (16 [20%] of 82 and 9 [23%] of 40), and thrombocytopenia (16 [20%] of 82 and 14 [35%] of 40). Most adverse events were considered unrelated to study drug. No treatment-related deaths were reported.; Interpretation: In this population of patients with non-haematological malignancies who are relatively chemotherapy naive, chemotherapy-induced thrombocytopenia treatment outcomes were similar between the avatrombopag and placebo groups. Given its safety and ability to augment platelet counts in patients with chemotherapy-induced thrombocytopenia, evaluation of avatrombopag in populations with more persistent chemotherapy-induced thrombocytopenia is warranted.; Funding: Dova Pharmaceuticals, a Sobi company.; Competing Interests: Declaration of interests HA-S reports grants, personal fees, and consultancy fees from Dova Pharmaceuticals (a Sobi company), during the conduct of the study; personal fees from Agios, Argenx, Rigel, Novartis, Moderna, and Forma; and grants from Agios and Amgen, outside the submitted work. XX and BDJ are employees of Dova Pharmaceuticals. JK-S and SZS declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alsbjerg, B., et al. (2023). "Rectal progesterone administration secures a high ongoing pregnancy rate in a personalized Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) protocol: a prospective interventional study." Human reproduction (Oxford, England) 38(11): 2221-2229.
	Study Question: Can supplementation with rectal administration of progesterone secure high ongoing pregnancy rates (OPRs) in patients with low serum progesterone (P4) on the day of blastocyst transfer (ET)?; Summary Answer: Rectally administered progesterone commencing on the ET day secures high OPRs in patients with serum P4 levels below 35 nmol/l (11 ng/ml).; What Is Known Already: Low serum P4 levels at peri-implantation in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles impact reproductive outcomes negatively. However, studies have shown that patients with low P4 after a standard vaginal progesterone treatment can obtain live birth rates (LBRs) comparable to patients with optimal P4 levels if they receive additionalsubcutaneous progesterone, starting around the day of blastocyst transfer. In contrast, increasing vaginal progesterone supplementation in low serum P4 patients does not increase LBR. Another route of administration rarely used in ART is the rectal route, despite the fact that progesterone is well absorbed and serum P4 levels reach a maximum level after ∼2 h.; Study Design, Size, Duration: This prospective interventional study included a cohort of 488 HRT-FET cycles, in which a total of 374 patients had serum P4 levels ≥35 nmol/l (11 ng/ml) at ET, and 114 patients had serum P4 levels <35 nmol/l (11 ng/ml). The study was conducted from January 2020 to November 2022.; Participants/materials, Setting, Methods: Patients underwent HRT-FET in a public Fertility Clinic, and endometrial preparation included oral oestradiol (6 mg/24 h), followed by vaginal micronized progesterone, 400 mg/12 h. Blastocyst transfer and P4 measurements were performed on the sixth day of progesterone administration. In patients with serum P4 <35 nmol/l (11 ng/ml), 'rescue' was performed by rectal administration of progesterone (400 mg/12 h) starting that same day. In pregnant patients, rectal administration continued until Week 8 of gestation, and oestradiol and vaginal progesterone treatment continued until Week 10 of gestation.; Main Results and the Role of Chance: Among 488 HRT-FET single blastocyst transfers, the mean age of the patients at oocyte retrieval (OR) was 30.9 ± 4.6 years and the mean BMI at ET 25.1 ± 3.5 kg/m2. The mean serum P4 level after vaginal progesterone administration on the day of ET was 48.9 ± 21.0 nmol/l (15.4 ± 6.6 ng/ml), and a total of 23% (114/488) of the patients had a serum P4 level lower than 35 nmol/l (11 ng/ml). The overall, positive hCG rate, clinical pregnancy rate, OPR week 12, and total pregnancy loss rate were 66% (320/488), 54% (265/488), 45% (221/488), and 31% (99/320), respectively. There was no significant difference in either OPR week 12 or total pregnancy loss rate between patients with P4 ≥35 nmol/l (11 ng/ml) and patients with P4 <35 nmol/l, who received rescue in terms of rectally administered progesterone, 45% versus 46%, P = 0.77 and 30% versus 34%, P = 0.53, respectively. OPR did not differ whether patients had initially low P4 and rectal rescue or were above the P4 cut-off. Logistic regression analysis showed that only age at OR and blastocyst scoring correlated with OPR week 12, independently of other factors like BMI and vitrification day of blastocysts (Day 5 or 6).; Limitations, Reasons for Caution: In this study, vaginal micronized progesterone pessaries, a solid pessary with progesterone suspended in vegetable hard fat, were used vaginally as well as rectally. It is unknown whether other vaginal progesterone products, such as capsules, gel, or tablet, could be used rectally with the same rescue effect.; Wider Implications of the Findings: A substantial part of HRT-FET patients receiving vaginal progesterone treatment has lowserum P4. Adding rectally administered progesterone in these patients increases the reproductive outcome. Importantly, rectal progesterone administration is considered convenient, and progesterone pessaries are easy to administer rectally and of low c st.; Study Funding/competing Interest(s): Gedeon Richter Nordic supported the study with an unrestricted grant as well as study medication. B.A. has received unrestricted grant from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA and Marckyrl Pharma. P.H. has received honoraria for lectures from Gedeon Richter, Merck, IBSA and U.S.K. has received grant from Gedeon Richter Nordic, IBSA and Merck for studies outside this work and honoraria for teaching from Merck and Thillotts Pharma AB and conference expenses covered by Merck. The other co-authors have no conflict of interest to declare.; Trial Registration Number (25): EudraCT no.: 2019-001539-29. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Alsbjerg, B., et al. (2022). "GnRH agonist supplementation in hormone replacement therapy-frozen embryo transfer cycles: a randomized controlled trial." Reproductive Biomedicine Online 44(2): 261-270.
	Research Question: Will two boluses of gonadotrophin-releasing hormone agonist (GnRHa) during hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles reduce the total pregnancy loss rate?; Design: Randomized controlled trial including a total of 287 HRT-FET cycles performed between 2013 and 2019. After randomization participants allocated to the GnRHa group (n = 144) underwent a standard HRT protocol, supplemented with a total of two boluses of triptorelin 0.1 mg; one bolus 2 days before starting vaginal progesterone and one bolus on the 7th day of progesterone. The control group (n = 143) underwent a standard HRT-FET protocol only.; Results: The intention-to-treat analysis showed no significant difference in total pregnancy loss between the GnRHa group and the control group (21% versus 33%; relative risk [RR] 0.63, 95% confidence interval [CI] 0.35-1.11), nor was the biochemical pregnancy loss per positive human chorionic gonadotrophin (HCG) significantly lower in the GnRHa group (12%, 8/67) compared with the control group (25%, 18/72) (RR 0.48, 95% CI 0.22-1.02). Participants with a live birth had a significantly higher mean progesterone concentration compared with participants without a live birth (25.0 ± 12.2 versus 23.8 ± 8.9 nmol/l; P = 0.001). Furthermore, a trend for a higher live birth rate (LBR) correlated with the highest oestradiol quartile concentration (oestradiol >0.957 nmol/l).; Conclusions: Although a difference of 14% in biochemical loss and 12% in total pregnancy loss in favour of GnRHa supplementation was seen this did not reach statistical difference. Luteal progesterone and oestradiol concentrations correlate with LBR in the HRT-FET cycle, emphasizing the importance of luteal serum progesterone and oestradiol monitoring. (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Alshammari, E. (2021). "The efficacy of zinc supplementation in postpartum depression: A review of studies on pregnancy and postdelivery care." International Journal of Pharmaceutical Research 13(1): 3162-3165.
	Depression is a major public health issue concerning many women during and after pregnancy. Most research studies indicate a prospective role of zinc in decreasing or inhibiting such depressive indications. Several investigations have evaluated the link between low zinc levels and depression. However, there are limited clinical trials examining zinc supplementation in depressed women before and after pregnancy. As a result, the review put together findings from some of the published studies on the effectiveness of zinc supplementation in the reduction or deterrence of depressive symptoms. Studies discussed in this paper were searched on Pubmed. In some of the studies, support for the effectiveness of zinc supplements on depressive indications was noted. However, in most of the studies, zinc supplementation was used as an adjunct of antidepressants drug treatment and was found to lower depressive symptoms significantly. The current study is limited in various ways. Currently, there are only a few trials investigating the impact of women taking zinc supplements to alleviate depressive symptoms before and after pregnancy. It is not possible to upgrade this review into a systematic review since a general pooled estimation of effect cannot be determined. In summary, it was evident from this review that zinc supplementation has potential benefits for depression, either as an independent intervention or as an addition to traditional antidepressant drug therapy. Even so, existing studies have several methodological challenges and there is need for additional well-designed studies evaluating zinc supplementation during pregnancy and post-delivery care to prevent postpartum depression.Copyright © 2021, Advanced Scientific Research. All rights reserved.

Alshammari, E. (2021). "Magnesium supplementation for premenstrual syndrome and premenstrual dysphoric disorder." International Journal of Pharmaceutical Research 13(1): 486-490.
	Premenstrual syndrome and premenstrual dysphoric disorder have been linked with low dietary intake of some vitamins and minerals, one of them being magnesium. In this regard, a suitable treatment plan should include supplementation of magnesium to achieve optimal status. However, it is necessary to verify if magnesium is effective and safe to manage PMS symptoms. The purpose of this review was to explore more recent studies examining magnesium supplementation for PMS and PMDD. Some studies identified magnesium supplementation as one of the options useful in the management of PMS in a nonpharmacological way. It is clear from the review that most women diagnosed with PMS show compromised levels of magnesium. These showed the significance of paying close attention to the nutritional status of females experiencing PMS to alleviate associated symptoms. In some cases, magnesium was used in combination with vitamin B6. The findings showed that magnesium combined with vitamin B6 had the biggest effect on PMS symptoms. Magnesium was more effective in controlling symptoms associated with water retention, craving, and anxiety. This mineral was also found to be valuable, low cost, and an effective treatment for PMS symptoms. In sum, evidence from most of the studies showed that magnesium could confer benefits to women who complain of premenstrual symptoms. The quality of some of the reviewed studies was questionable and it is necessary that well-designed randomized controlled trials are carried out to determine the effect of magnesium supplementation among women with PMS and PMDD. Hence, further investigations need to be carried out before encouraging the prescription of magnesium supplements for PMS and PMDD.Copyright © 2020, Advanced Scientific Research. All rights reserved.

Alsharif, S. A., et al. (2024). "Effect of Oral Consumption of Vitamin D on Uterine Fibroids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials." Nutrition and Cancer 76(3): 226-235.
	Impaired vitamin D status is highly prevalent among women with UFs. The objective of this first-ever systematic review and meta-analysis was to summarize the effect of vitamin D supplementation on the size of uterine fibroids (UFs). We performed a comprehensive literature search for published randomized controlled trials (RCTs) in Medline, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 2022. Five trials including 511 participants (256 cases and 255 controls) were included. Pooling results from five trials, which compared size of UFs between experimental and placebo groups, revealed that vitamin D supplementation could significantly decrease the size of UFs (standardized mean difference [SMD]: -0.48, 95% confidence interval [CI]: -0.66, -0.31) and cause improvement in serum level of vitamin D compared to placebo group (SMD: 3.1, 95% CI: 0.66, 5.55). A significant effect was observed in the subset of trials administering vitamin D supplementation for >8 wk (SMD: -0.62, 95% CI: -0.88, -0.37). In conclusion, vitamin D supplementation significantly increases serum levels of vitamin D and reduces the size of UFs. However, larger, well-designed RCTs are still needed to determine the effect of vitamin D on other parameters of UFs.Copyright © 2024 Taylor & Francis Group, LLC.

Alsulihem, A. and J. Corcos (2021). "The use of vaginal lasers in the treatment of urinary incontinence and overactive bladder, systematic review." International Urogynecology Journal 32(3): 553-572.
	Objectives: To evaluate the available literature to assess the safety, efficacy, and outcomes of lasers in the treatment of female stress urinary incontinence (SUI) and overactive bladder (OAB). Method(s): Pubmed search was conducted up to May 2020, including observational and investigational human studies that documented the effects on laser treatment in SUI and OAB. Result(s): A total of 27 studies, recording subjective or objective measures in SUI or OAB were included. Lasers used included Er:YAG and Fractional CO2 lasers. The overall quality of studies was poor, and 23/27 studies were case series (LOE:4). Er:YAG laser showed a modest reduction in mild SUI cases, with benefits lasting a maximum of 13-16 months. Er:YAG laser for OAB showed conflicting results, with a trend to improve OAB symptoms for up to 12 months. Fractional CO2 laser showed an improvement of mild SUI in few studies; however, no long-term data are available. For OAB symptoms, studies showed minimal improvement that was evaluated in short term studies. When reported, adverse events were insignificant, however, they were not reported systematically. Several limitations have been noticed in the current literature of vaginal lasers, including large variation in laser settings and protocols, short term follow up, lack of urodynamic evaluation, and appropriate objective measures. Conclusion(s): Based on the available literature, lasers cannot be recommended as a treatment option at this time. Future better-quality studies are needed to document the exact mechanism of action, longevity, safety and its eventual place into the current treatment algorithms of SUI and OAB.Copyright © 2020, The International Urogynecological Association.

Al-Taie, M. J. M., et al. (2021). "Medical induction of first trimester abortion by misoprostol or misoprostol with letrozole." Indian journal of forensic medicine and toxicology 15(1): 2712‐2717.
	Background: Managing of abortion is an important subject in gynecology. Millions of patients had suffered from spontaneous abortions that occur per year. Objective(s): The aim of this study was to compare the effect of misoprostol alone and misoprostol with letrozole in the induction of abortion in the first trimester of pregnancy. Patients and Methods: In a single ‐blind clinical trial,128 female applicants for legal abortion within the first trimester of pregnancy that referred to AL‐Batool hospital, were divided in to two groups: intervention (misoprostol with letrozole) and control groups (misoprostol alone). The complete abortion, drug‐induced side effects of misoprostol and letrozole were noted and evaluated. Result(s): The complete abortion rate was93.2% in intervention group and in68.7% in the control group (misoprostol) only, which was significantly higher in intervention group (p = 0.001). Abdominal pain in the intervention group is also significantly lower than that of the control group (p = 0.013). Intervention group also had significantly lower duration of bleeding rather than control group (p = 0.006). Conclusion(s): Based on our results, pretreatment with letrozole plus Misoprostol was more effective for prompting abortion in the first trimester of pregnancy without increasing side effect compared to misoprostol alone. Copyright © 2021, Institute of Medico‐Legal Publications. All rights reserved.

Alteri, A., et al. (2024). "ESHRE guideline: number of embryos to transfer during IVF/ICSI+." Human reproduction (Oxford, England).
	STUDY QUESTION: Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)? SUMMARY ANSWER: No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI. WHAT IS KNOWN ALREADY: DET is correlated with a higher rate of multiple pregnancy, leading to a subsequent increase in complications for both mother and babies. These complications include preterm birth, low birthweight, and other perinatal adverse outcomes. To mitigate the risks associated with multiple pregnancy, eSET is recommended by international and national professional organizations as the preferred approach in ART. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development and update of ESHRE guidelines. Literature searches were performed in PUBMED/MEDLINE and Cochrane databases, and relevant papers published up to May 2023, written in English, were included. Live birth rate, cumulative live birth rate, and multiple pregnancy rate were considered as critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were discussed until a consensus was reached within the Guideline Development Group (GDG). A stakeholder review was organized after the guideline draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 35 recommendations on the medical and non-medical risks associated with multiple pregnancies and on the clinical and embryological factors to be considered when deciding on the number of embryos to transfer. These recommendations include 25 evidence-based recommendations, of which 24 were formulated as strong recommendations and one as conditional, and 10 good practice points. Of the evidence-based recommendations, seven (28%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (three recommendations; 12%), or very low-quality evidence (15 recommendations; 60%). Owing to the lack of evidence-based research, the guideline also clearly mentions recommendations for future studies. LIMITATIONS, REASONS FOR CAUTION: The guideline assessed different factors one by one based on existing evidence. However, in real life, clinicians' decisions are based on several prognostic factors related to each patient's case. Furthermore, the evidence from randomized controlled trials is too scarce to formulate high-quality evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides health professionals with clear advice on best practice in the decision-making process during IVF/ICSI, based on the best evidence currently available, and recommendations on relevant information that should be communicated to patients. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTEREST(S): The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, the literature searches, and the dissemination of the guideline. The guideline group members did not receive payment. DPB declared receiving honoraria for lectures from Merck, Ferring, and Gedeon Richter. She is a member of ESHRE EXCO, and the Mediterranean Society for reproductive medicine and the president of the Croatian Society for Gynaecological Endocrinology and Reproductive Medicine. CDG is the past Chair of the ESHRE EIM Consortium and a paid deputy member of the Editorial board of Human Reproduction. IR declared receiving reimbursement from ESHRE and EDCD for attending meetings. She holds an unpaid leadership role in OBBCSSR, ECDC Sohonet, and AER. KAR-W declared receiving grants for clinical researchers and funding provision to the institution from the Swedish Cancer Society (200170F), the Senior Clinical Investigator Award, Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council FoU (Fo I-953912) and Karolinska Institutet (Dnr 2020-01963), NovoNordisk, Merck and Ferring Pharmaceuticals. She received consulting fees from the Swedish Ministry of Health and Welfare. She received honoraria from Roche, Pfizer, and Organon for chairmanship and lectures. She received support from Organon for attending meetings. She participated in advisory boards for Merck, Nordic countries, and Ferring. She declared receiving time-lapse equipment and grants with payment to institution for pre-clinical research from Merck pharmaceuticals and from Ferring. SS-R received research funding from Roche Diagnostics, Organon/MSD, Theramex, and Gedeo-Richter. He received consulting fees from Organon/MSD, Ferring Pharmaceuticals, and Merck Serono. He declared receiving honoraria for lectures from Ferring Pharmaceuticals, Besins, Organon/MSD, Theramex, and Gedeon Richter. He received support for attending Gedeon Richter meetings and participated in the Data Safety Monitoring Board of the T-TRANSPORT trial. He is the Deputy of ESHRE SQART special interest group. He holds stock options in IVI Lisboa and received equipment and other services from Roche Diagnostics and Ferring Pharmaceuticals. KT declared receiving payment for honoraria for giving lectures from Merck Serono and Organon. She is member of the safety advisory board of EDQM. She holds a leadership role in the ICCBBA board of directors. ZV received reimbursement from ESHRE for attending meetings. She also received research grants from ESHRE and Juhani Aaltonen Foundation. She is the coordinator of EHSRE SQART special interest group. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (full disclaimer available at https://www.eshre.eu/Guidelines-and-Legal).Copyright © The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

Alteri, A., et al. (2020). "ALADDIN study: does assisted hatching of vitrified/warmed blastocysts improve live birth rate? Protocol for a multicentric randomised controlled trial." BMJ Open 10(7): e031544.
	Introduction: Recent data suggest a higher clinical pregnancy rate performing assisted hatching (AH) on previously cryopreserved embryos but fail to demonstrate significant effects on live birth rate. However, current evidence is based on studies with a small sample size and may hide a type II error. Moreover, poor attention has been given to the specific effect of AH on frozen/thawed blastocysts. To shed light on this topic, we developed the present protocol for a randomised trial to investigate the benefits of the laser-mediated partial removal of the zona pellucida in vitrified/warmed blastocysts.; Methods and Analysis: The pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN) study is a multicentric prospective comparative study with a parallel randomised controlled design aiming to investigate whether AH performed on warmed blastocysts before embryo transfer can improve live birth rate. Women allocated to the control group will undergo embryo transfer of blastocysts not previously subjected to AH. Two infertility units will be involved in the study. Enrolment of patients will last 18 months with quarterly monitoring and the entire study is foreseen to be closed in 36 months. Secondary outcomes include: proportion of transferred blastocysts/thawed blastocyst, morphological features of blastocysts before embryo transfer, implantation, biochemical pregnancy, clinical pregnancy (ultrasound visible gestational sac), miscarriage, multiple pregnancy, preterm birth (<37 weeks of gestation), obstetrical and neonatal complications and congenital anomaly rates.; Ethics and Dissemination: This protocol received a favourable ethical opinion from the Ethical Committee of IRCCS San Raffaele Scientific Institute and the Ethical Committee Area 2 Milan. Each participant will provide written consent to participate and remain encoded during the study. The trial results will be published in peer-reviewed journals and presented at conferences.; Trial Registration Number: NCT03623659; Pre-results.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Alteri, A., et al. (2024). "The effect of laser-assisted hatching on vitrified/warmed blastocysts: the ALADDIN randomized controlled trial." Fertility and Sterility.
	Objective: To evaluate whether laser-mediated assisted hatching (AH) performed on vitrified/warmed blastocysts before embryo transfer can improve live birth rate.; Design: The "pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN)" is a 2-center comparative study with a parallel randomized controlled design.; Setting: University hospital.; Patients: Participants were recruited between September 2018 and November 2021. They were aged 18-39 years, underwent nondonor in vitro fertilization cycles, and were scheduled for elective single embryo transfer with vitrified/warmed blastocysts. Those with uterine abnormalities, body mass index of >35 kg/m 2 , severe male factor infertility, or performing preimplantation genetic testing were excluded.; Intervention: Assisted hatching was performed using a 1,480 nm diode laser, removing approximately one-third of the zona pellucida with continuous 0.2 ms pulses applied from the 1-5 o'clock positions.; Main Outcome Measures: The primary outcome was the live birth rate. Secondary end points included clinical pregnancy, miscarriage, multiple pregnancies, preterm births, obstetric and neonatal complications, and congenital anomalies.; Results: Overall, 698 participants met the inclusion criteria and were randomized: 352 patients were assigned to the AH arm and 346 to the control arm. Of the participants, 105 (29.8%) and 101 (29.2%), respectively, achieved a live birth after treatment. The relative risk of live birth in patients with vitrified/warmed blastocysts treated with AH was 1.02 (95% confidence interval, 0.86-1.19). Exploratory subgroup analyses for women's age, recruiting centers, indications for in vitro fertilization, method of insemination, blastocyst quality, and days of blastocyst development failed to highlight any clinical situation that could benefit from AH in thawed blastocysts.; Conclusion: In patients undergoing frozen embryo transfer with vitrified/warmed blastocysts, laser AH does not improve the live birth rate. Further studies are required to rule out milder but potentially interesting benefits in specific subgroups of patients.; Trial Registration: ClinicalTrials.gov: NCT03623659.; Competing Interests: Declaration of Interests E.P. reported grants and personal fees from MSD, grants from Ferring, IBSA, TEVA, and Gedeon Richter, grants and personal fees from Merck. P.V. received honoraria for editorial engagements. E.S. received honoraria for presentations at meetings from IBSA and Gedeon Richter, and also is handling 2 research grants from Ferring and IBSA. A.A. has nothing to disclose. M.R. has nothing to disclose. C.G. has nothing to disclose. V.B. has nothing to disclose. G.B. has nothing to disclose. M.P. has nothing to disclose. E.R. has nothing to disclose. S.F. has nothing to disclose. A.P. has nothing to disclose. (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Althanoon, Z. A. (2021). "Metabolic and hormonal effects of rosiglitazone in overweight women with PCOS." Turkish journal of physiotherapy and rehabilitation 32(3): 10963‐10968.
	Objective: Polycystic ovary syndrome(PCOS) is the most common hormonal disorder which mostly affects women of childbearing ages. Almost,women with this syndrome, insulin sensitizing drugs can have both beneficial hormonal and biochemical effects. Hence, the objective of this research was to assess and compare the effects of insulin sensitizing drug, rosiglitazone, on hormonal and biochemical profiles in patients with PCOS. Methods: In this simple randomization study, approximately, one hundred and twenty subjects were enrolled in this study, they were divided into two groups of 60 subjects each. The patients' group were received rosiglitazone treatment for three months (4‐5mg/day) and the other 60 were the control group which included apparently healthy volunteers. Hormonal profiles (serum testosterone, serum insulin, HOMA‐IR and serum resistin) and biochemical profiles (fasting serum glucose and lipid profile), in addition to body weight, height, body mass index, and even blood pressure were evaluated before and after treatment for both the patient and control groups. Results:The current study found a that there was a significant increase in the mean of body mass index (BMI), serum levels of glucose, insulin, testosterone, resistin, lipid profile (TC, HDL, LDL, TG) in addition to systolic and diastolic blood pressure in women with PCOS prior to rosiglitazone in comparison to controls. Whereas after drug therapy the patient experienced a significant decrease in all of the studied parameters associated with insulin resistance improvement, as well as a nonsignificant decrease in serum testosterone level. Conclusion: This study found that treating women with PCOS with rosiglitazone resulted in a decrease in hormonal profiles of serum insulin and serum testosterone, as well as an improvement in metabolic profiles, indicating the potential benefit of this drug in the treatment of PCOS patients.

Alur-Gupta, S., et al. (2019). "Two-Dose Versus Single-Dose Methotrexate for Treatment of Ectopic Pregnancy: A Meta-analysis." Obstetrical and Gynecological Survey 74(12): 716-717.
	
Alvisi, S., et al. (2022). "Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy." The Journal of Sexual Medicine 19(5): 761-770.
	Background: Among treatments for vulvo-vaginal atrophy (VVA), there is a new kind of energy-based device, the non-ablative CO 2 laser.; Aim: This study aimed to assess the efficacy and safety of the non-ablative CO 2 laser in menopausal women with VVA as a monotherapy or in association with vaginal estriol or moisturizer.; Methods: Seventy-five women with VVA received laser treatment (Laser group), laser plus estriol gel (Laser+E) or laser plus moisturizers (Laser+M). The study protocol consisted of 3 monthly laser sessions (t0, t1, t2) and a gynecological examination at baseline and 1 month after last laser treatment (t3). Objective measures included VHI (Vaginal Health Index) and VuHI (Vulvar Health Index); subjective symptoms of VVA (Dryness, Burning, Itching, Dysuria) evaluated via visual analog scales, sexual function evaluated by FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Score) and MENQOL (Mopause-specific Quality Of Life). Adverse events and discomfort encountered during the procedure were also assessed.; Outcomes: Primary outcomes were the evaluation of VHI and VuHI and secondary outcomes were changes in VVA symptoms (VAS), sexual function (MENQOL, FSFI, FSDS) and discomfort during the procedure.; Results: Seventy-five women (25 in Laser, 25 in Laser+E and 25 in Laser+M group) completed the study. At t3, mean VHI, VuHI, dryness, burning and itching VAS scores improved significantly with no differences between the groups. The lubrication domain of FSFI improved significantly only in the Laser+M group, while the pain domain improved significantly in all women with no differences between the groups. FSFI and FSDS overall scores and MENQOL sexual domain improved in all women with no significant difference between the groups. The mean score of the pain during the procedure was low at t0 and did not change throughout the study.; Clinical Implications: This study extends knowledge concerning the effectiveness of a new non-ablative CO 2 laser in post-menopausal women with VVA.; Strengths & Limitations: This is one of the first studies on this kind of laser and is the first to compare the effectiveness of laser treatment alone or in combination with vaginal estriol or moisturizers. Parameters of VVA and sexual function were evaluated using validated tools. Study limitations include short follow-up time, the limited number of participants and the absence of a sham-controlled group.; Conclusion: Non-ablative CO 2 laser seems to be an effective treatment for VVA in menopausal women. Our preliminary data shows that it can be effective as monotherapy or with adjuvant treatments. Alvisi S, Lami A, Baldassarre M, et al. Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy. J Sex Med 2022;19:761-770. (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Alyami, M., et al. (2019). "Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications." The Lancet. Oncology 20(7): e368-e377.
	Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Alyanak, A., et al. (2022). "Comparison of botulinum toxin (BoNT) injection and lateral internal sphincterotomy (redo-LIS) for recurrent anal fissure treatment." Frontiers in surgery 9: 988082.
	Objective: Today's gold standard for treating chronic anal fissure is the Lateral Internal Sphincterotomy (LIS). Botulinum Toxin (BoNT) injection is, on the other hand, an alternative treatment for patients who do not want to have surgical treatment, patients undergoing chemotherapy, patients of high risk for surgery, and those who have the risk of anal incontinence (e.g., elderly, past anorectal surgery, vaginal multiple births, etc.). The aim of this study is to compare the effectiveness of BoNT and redo-LIS for treatment of post-LIS recurrent chronic anal fissure, and reveal differences if any.This study aims to compare redo-LIS and BoNT injection for treating post-LIS recurrent anal fissure.; Material and Method: Nineteen patients who received LIS treatment and then redo-LIS or BoNT injection due to recurrence in the follow-up were included in this study. Group I (redo-LIS group) include 11 patients and group 2 (BoNT group) includes 8 patients. Their data on age, sex, anal incontinence scores and pain (VAS score) score as well.; Results: During the 3-month post-surgery follow-up period, there was statistically significant difference ( p < 0.01) between groups by pain. No deterioration in the incontinence scores of patients in the group during the 6-month post-surgery period.; Conclusion: This study demonstrates that redo lateral internal sphincterotomy (LIS) is a reliable method for patients who received LIS but developed recurrent chronic anal fissure, and achieves successful results in terms of recurrence and relief of pain.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2022 Alyanak, Gulen and Ege.)

Amani, B., et al. (2024). "Public health nurse-delivered cognitive behavioral therapy for postpartum depression: Assessing the effects of maternal treatment on infant emotion regulation." Development and psychopathology: 1-9.
	The effects of maternal postpartum depression (PPD) on offspring emotion regulation (ER) are particularly deleterious as difficulties with ER predict an increased risk of psychopathology. This study examined the impact of maternal participation in a public health nurse (PHN)-delivered group cognitive behavioral therapy (CBT) intervention on infant ER. Mothers/birthing parents were >= 18 years old with an Edinburgh Postnatal Depression Scale (EPDS) score >= 10, and infants were < 12 months. Between 2017 and 2020, 141 mother-infant dyads were randomized to experimental or control groups. Infant ER was measured at baseline (T1) and nine weeks later (T2) using two neurophysiological measures (frontal alpha asymmetry (FAA) and high-frequency heart rate variability (HF-HRV)), and informant-report of infant temperament. Mothers were a mean of 30.8 years old (SD = 4.7), 92.3% were married/ common-law, and infants were a mean of 5.4 months old (SD = 2.9) and 52.1% were male. A statistically significant group-by-time interaction was found to predict change in HF-HRV between T1 and T2 (F(1,68.3) = 4.04, p = .04), but no significant interaction predicted change in FAA or temperament. Results suggest that PHN-delivered group CBT for PPD may lead to adaptive changes in a neurophysiological marker of infant ER, highlighting the importance of early maternal intervention.

Amani, B., et al. (2022). "Peer-Delivered Cognitive-Behavioral Therapy for Postpartum Depression: A Randomized Controlled Trial." Journal of Clinical Psychiatry 83(1): 21m13928.
	Objective: To determine if a 9-week group cognitive-behavioral therapy (CBT) intervention delivered by women who have recovered from postpartum depression (peers) can effectively reduce symptoms of postpartum depression (PPD) and anxiety and improve social support and the mother-infant relationship. Method(s): A sample of 73 mothers living in Ontario, Canada, were randomized into experimental and waitlist control groups between March 2018 and February 2020. Participants were >= 18 years of age, had an infant < 12 months old, were fluent in English, and scored >= 10 on the Edinburgh Postnatal Depression Scale. The experimental group completed the 9-week group CBT intervention immediately after study enrollment, while the control group did so after a 9-week waiting period. All outcomes were assessed at enrollment (n = 54) and 9 weeks later (n = 38). Outcomes were assessed in the experimental group at 6 months to assess treatment stability. Result(s): Peer-delivered group CBT for PPD led to clinically and statistically significant improvements in symptoms of depression (F1,47 = 22.52, P< .01) and anxiety (F1,45 = 20.56, P< .05) in the experimental group, and these improvements were stable at the 6-month follow-up. Perceptions of impaired mother-infant bonding (t15 = 3.72, P< .01) and rejection and pathological anger (t15 = 3.01, P< .01) also decreased at the 6-month follow-up in the experimental group. Conclusion(s): Peer-delivered group CBT for PPD effectively treats symptoms of PPD and anxiety and may lead to improvements in the mother-infant relationship. This intervention is an effective and potentially scalable means by which access to a treatment that meets the needs and wants of mothers with PPD can be increased.© Copyright 2021 Physicians Postgraduate Press, Inc.

Amaya, S. and J. Shorter (2023). "Early Pregnancy Assessment Clinics: Expanding Patient-Centered and Equitable Early Pregnancy Care." Current Obstetrics and Gynecology Reports 12(2): 96-102.
	Purpose of Review: This review provides an overview of how early pregnancy assessment clinics (EPACs) provide patient-centered and evidence-based early pregnancy care, increase access to abortion care, and reduce health disparities. Recent Findings: There is growing evidence that early pregnancy care provided in an EPAC is cost-effective, patient centered, and highly valued by patients. Summary: Patients in the USA who have clinical needs in early pregnancy often do not have a standard location to seek care. EPACs have been shown to provide early pregnancy care that is efficient and compassionate while also promoting patient autonomy and increasing access to standardized early pregnancy loss and abortion care. EPACs, while underutilized in the USA, should be integrated into the health system to expand the availability of quality early pregnancy care.Copyright © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Ambacher, K., et al. (2022). "The use of progestin subdermal implants in the management of endometriosis-related pain symptoms and quality of life: a systematic review." Current medical research and opinion 38(3): 479-486.
	Objective: The purpose of this systematic review is to evaluate the evidence for the use of progestin subdermal implants for the treatment of endometriosis-related pain symptoms and quality of life.; Methods: A literature search of PubMed, Ovid (MEDLINE and EMBASE), and Web of Science was performed from inception to December 2020. In addition, a targeted search of cited references was also performed. Our search identified 330 articles of which 17 were deemed eligible for full-text review. Eligible studies included randomized control trials, observational studies, and case series with at least 5 cases, investigating the effect of progestin subdermal implants on endometriosis-related pain scores in women of reproductive age with a clinical, radiologic, or surgical diagnosis of endometriosis. Six articles were excluded after the full-text screen.; Results: Eleven articles describing a total of 335 patients were eligible for inclusion. Across all studies, etonogestrel- and segesterone-releasing progestin subdermal implants improved VAS pain scores for cyclic pelvic pain/dysmenorrhea (VAS at baseline ranged from 6.1 to 7.5 cm and after treatment from 1.7 to 4.9 cm, n = 121), non-cyclic pelvic pain (baseline VAS 7.2-7.6 cm and after treatment 2.0-3.7 cm, n = 96) and dyspareunia (baseline VAS 1.61-8.3 cm and after treatment 1.0-7.1 cm, n = 87). Symptom improvement with the progestin subdermal implant was equivalent to treatment with depot medroxyprogesterone acetate (DMPA; average baseline VAS 6.5 and after DMPA treatment 3.0, compared to 2.0 after treatment with the implant) or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS; baseline cyclic and non-cyclic pain scores 7.3 and 7.4 respectively decreased to 1.9 and 1.9 after LNG-IUS treatment). Improvements were also demonstrated in quality-of-life scores (average improvement of 36% in all domains of the Endometriosis Health Profile-30 and significant improvements in social functioning, general health, bodily pain, vitality and mental health domains on the Short Form-36 questionnaire) and sexual function (total sexual function score improved from 24 to 25.35 and 26.25 at 6 and 12 months).; Conclusion: Etonogestrel- and segesterone-releasing progestin subdermal implants appear to improve endometriosis-related pain symptoms and quality of life and may provide an additional component in the management of endometriosis. However, this systematic review is limited by the small sample size and heterogeneity in the data. As such, larger prospective randomized trials are needed to guide further management.; Prospero Registration: CRD42021225665.

Ambrogio, P. L. and C. Angelo (2023). "Hormonal Therapy in Post-menopausal Women and the Effect of Progestins on Depression, Mood, Anxiety, and Quality of Life."
	
Amerigo, V., et al. (2023). "Does recipients endometriosis influences the live birth rate in oocyte donation cycles: a systematic review and meta-analysis."
	
Amin, H. L., et al. (2022). "The effects of ketogenic diet on the outcomes of polycystic ovary syndrome: A systematic review on clinical trials." Iranian Journal of Obstetrics, Gynecology and Infertility 25(7): 128-138.
	Introduction: Polycystic ovary syndrome is a major cause of anovulation and infertility in women that is associated with chronic diseases such as obesity, insulin resistance, diabetes, cardiovascular disease, and fatty liver disease. This systematic review was performed aimed to determine the effects of ketogenic diet on the outcomes of polycystic ovary syndrome. Method(s): In this systematic review, the keywords of "polycystic ovary syndrome", "ketogenic diet", "low carbohydrate diet", and "clinical trials" were searched in databases of Medline, PubMed, Science Direct, Magiran, ISD, ISC and Cochrane in English and Persian language without time restrictions. Then, the articles relevant to the study's aim were reviewed. Result(s): In this research, 4 studies were examined. The results showed that following a ketogenic diet in patients with polycystic ovary syndrome may reduce the risk of cardiovascular diseases in these patients by lowering weight and body mass index, blood pressure, serum total cholesterol, and triglycerides. Conclusion(s): Long-term adherence to a ketogenic diet may result in weight loss, improved insulin resistance, and serum lipid profile disorders in patients with polycystic ovary syndrome. Clinical trials are suggested to evaluate the effects of ketogenic diet on these metabolic and endocrine factors in PCOS women.Copyright © 2022, Mashhad University of Medical Sciences. All rights reserved.

Amin, M., et al. (2021). "Phase I Study of Docetaxel and Temsirolimus in Refractory Solid Tumors." American Journal of Clinical Oncology 44(9): 443-448.
	INTRODUCTION: The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors. We conducted a phase I open-label, dose-escalation study to determine the maximal tolerated dose (MTD) of docetaxel in combination with temsirolimus in patients with refractory solid tumors. PATIENTS AND METHODS: Eligible patients had a diagnosis of a refractory solid malignancy, measurable disease, and adequate organ function. Patients were sequentially enrolled in 4 dose level intravenous combinations of docetaxel and temsirolimus. Temsirolimus was administered weekly with docetaxel administered every 3 weeks. Laboratory data for tumor markers and radiologic imaging were conducted prestudy and then after every 2 cycles of the treatment. Radiologic response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Blood samples for PK and pharmacodynamic analysis were planned to be drawn at MTD. Apart from the traditional 3+3 design, we also implemented Bayesian Optimal Interval design which uses isotonic regression method to select MTD. We proceeded with isotonic regression analysis by using 20% dose-limiting toxicity (DLT) rate as target. RESULTS: Twenty-six patients were treated in this study in 4 cohorts and dose levels. Fourteen males and 12 females were enrolled with a median age of 50 years (range of 27 to 72 y) and median Eastern Cooperative Oncology Group performance score of 1. Tumor histologies included pancreas (6), colon (5), rectum (3), gallbladder (2), non-small cell lung (2), endometrium (1), neuroendocrine (1), esophagus (1), stomach (1), pharynx (1), small intestine (1), and duodenum (1). Stable disease was observed in 2/4 (50%), 3/7 (43%), 4/10 (40%), and 3/5 (60%) patients in cohorts 1, 2, 3, and 4, respectively. Dose escalation in cohorts 2, 3, and 4 was complicated by DLTs such as grade 4 neutropenia and grade 3 diarrhea and an inability for patients to tolerate treatments during and beyond cycle 1 without dose reductions. Therefore, we could not determine an MTD or recommended phase II dose using the traditional 3+3 study analysis. Blood samples for PK and pharmacodynamic analysis were not collected since MTD was not determined. By using 20% DLT rate closest to the target, isotonic regression analysis showed identical estimated DLT rates in dose -1 (docetaxel 50 mg/m2 and temsirolimus 15 mg/m2) and dose level 1 (docetaxel 60mg/m2 and temsirolimus 15 mg/m2). CONCLUSIONS: Dose escalation of docetaxel and temsirolimus was limited by severe myelosuppressive toxicity in this phase I study. Most of the DLTs occurred after cycle 1 of therapy hence, we were unable to determine MTD or collect blood samples for PK and pharmacodynamic analysis. Our trial did not meet its objectives due to significant DLTs with this chemotherapy combination. Although our novel use of Bayesian Optimal Interval design using isotonic regression method to select MTD showed identical estimated DLT rates in dose levels 1 and -1, clinically our patients were not able to complete 2 cycles of this regimen without dose reductions due to myelosuppressive toxicity in either of these dose levels, and hence, escaped clinical validity. This combination regimen should not be studied further at the dose levels and schedules tested in our study.

Amini, S., et al. (2022). "The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial." Nutritional neuroscience 25(1): 22-32.
	Objectives: Postpartum depression (PPD) is a major depressive disorder. Vitamin D deficiency may play a role in PPD pathogenesis. This study was designed to determine the effect of vitamin D and calcium supplementation on the severity of symptoms and some related inflammatory biomarkers in women with PPD. Materials and Methods: Eighty-one women with a PPD score >12 participated in this study. A total of 27 patients were randomly assigned into three groups (1:1:1 ratio) to receive either 50,000 IU vitamin D3 fortnightly + 500 mg calcium carbonate daily; or 50,000 IU vitamin D3 fortnightly + placebo of calcium carbonate daily, or placebo of vitamin D3 fortnightly + placebo of calcium carbonate daily (placebo group) for 8 weeks. At the baseline and end of the study, the severity score of PPD, levels of 25-hydroxy vitamin D, calcium, tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6) and estradiol were measured. Results: The PPD score had more reduction in the vitamin D + calcium and vitamin D + calcium placebo groups than that of the placebo group (-1.7 ± 3.44, -4.16 ± 5.90 and 0.25 ± 2.81, respectively; p = 0.008). The effect of vitamin D on the PPD score was larger when vitamin D was given alone than given together with calcium ( p = 0.042 and p = 0.004, respectively). No significant differences in estradiol, IL6 and TNFα were observed between the three groups. Discussion: Vitamin D may be effective in improving the clinical symptoms of PPD; however, the mechanism of the effect might not entirely operate through inflammatory and/or hormonal changes.

Amini, S., et al. (2019). "Postpartum depression and vitamin D: A systematic review." Critical reviews in food science and nutrition 59(9): 1514-1520.
	Postpartum depression (PPD) is a prevalent mood disorder estimated to affect 20%-40% of women worldwide after childbirth. In recent studies, the effect of vitamin D on prevention of mood disorders and depression has been investigated, but it is still unclear how vitamin D may affect PPD. The evidence on the relevance between vitamin D deficiency and PPD is inconsistent, and assessment of the recent literature has not previously been carried out. Moreover, there are few clinical studies on PPD and vitamin D supplementation. Five studies have so far assessed the relationship between the levels of vitamin D and PPD. Findings from cohort studies suggest that vitamin-D deficiency is related to the incidence of PPD and vitamin D may play a significant role in the recovery of women with PPD, but it is uncertain whether these actions are the effect of vitamin D on the function of hypothalamic-pituitary-adrenal (HPA) axis, the levels of estradiol, serotonin, pro-inflammatory cytokines, and/or of other mechanisms involved in PPD.

amira, n., et al. (2022). "Manual therapy for myofascial pelvic pain syndrome:a systematic review."
	
Amiri, M., et al. (2022). "Whole-diet interventions and cardiovascular risk factors in postmenopausal women: A systematic review of controlled clinical trials." Maturitas 155: 40-53.
	Objectives: Menopause is accompanied by many metabolic changes, increasing the risk of cardiometabolic diseases. The impact of diet, as a modifiable lifestyle factor, on cardiovascular health in general populations has been well established. The purpose of this systematic review is to summarize the evidence on the effects of whole diet on lipid profile, glycemic indices, and blood pressure in postmenopausal women.; Methods: Embase, Medline, Cochrane Central Register of Controlled Trials, and Google Scholar were searched from inception to February 2021. We included controlled clinical trials in postmenopausal women that assessed the effect of a whole-diet intervention on lipid profile, glycemic indices, and/or blood pressure. The risk of bias in individual studies was assessed using RoB 2 and ROBINS-I tools.; Summary of Evidence: Among 2,134 references, 21 trials met all eligibility criteria. Overall, results were heterogenuous and inconsistent. Compared to control diets, some studies showed that participants experienced improvements in total cholesterol (TC), low-density lipoprotein cholesterol (LDL), systolic blood pressure (SBP), fasting blood sugar (FBS), and apolipoprotein A (Apo-A) after following fat-modified diets, but some adverse effects on triglycerides (TG), very low-density lipoprotein cholesterol (VLDL), lipoprotein(a) (Lp(a)), and high-density lipoprotein cholesterol (HDL) concentrations were also observed. A limited number of trials found some effects of the Paleolithic, weight-loss, plant-based, or energy-restricted diets, or of following American Heart Association recommendations on TG, TC, HDL, insulin, FBS, or insulin resistance.; Conclusion: Current evidence suggests that diet may affect levels of some lipid profile markers, glycemic indices, and blood pressure among postmenopausal women. However, due to the large heterogeneity in intervention diets, comparison groups, intervention durations, and population characteristics, findings are inconclusive. Further well-designed clinical trials are needed on dietary interventions to reduce cardiovascular risk in postmenopausal women. (Copyright © 2021. Published by Elsevier B.V.)

Amiri, M. and T. Ramezani (2020). "Comparison of the effects of combined oral contraceptives containing progestins with low androgenic and antiandrogenic activities on the clinical, androgenic, and metabolic manifestations of polycystic ovary syndrome." Iranian Journal of Endocrinology and Metabolism 22(1): 83-91.
	Introduction: Combined oral contraceptives (COCs) are commonly considered as the first-line treatment for polycystic ovary syndrome (PCOS). This study aimed to compare the effects of COCs with respect to their progestin component on the clinical, hormonal, and metabolic outcomes of women with PCOS. Data were extracted by searching PubMed, Scopus, EMBASE, and Google Scholar, without any time limitations (until 2020). All studies assessing the effects of COCs on PCOS patients of childbearing age were reviewed and discussed. Based on the findings, different types of COCs can improve hyperandrogenism and regulate the menstrual cycle by suppressing gonadotropins and increasing sex hormone-binding globulin. Compared to COCs containing androgenic progestins (e.g., desogestrel and levonorgestrel), COCs containing anti-androgenic progestins (e.g., cyproterone acetate and drospirenone) could reduce androgen deprivation through specific mechanisms. However, the available evidence does not support the superiority of these anti-androgenic compounds in improving the clinical manifestations of hyperandrogenism. While all COCs may be associated with lipid disorders, drospirenone-containing compounds seem to be associated with the fewest disorders. Also, as COCs may result in metabolic disorders, especially dyslipidemia, it is necessary to periodically measure metabolic parameters in COC-consuming patients.Copyright © 2020, Research Institute for Endocrine Sciences. All rights reserved.

Amiri, P., et al. (2019). "Application of distraction techniques in obstetrics and gynaecology: A systematic review." Journal of Clinical and Diagnostic Research 13(4): QE01-QE08.
	Introduction: International institutions have emphasised the role of midwives in ensuring women health, which guarantees family health and its physical, psychological, social, and spiritual aspects. The integration of midwifery knowledge with psychology is a good opportunity for the patients and healthcare providers. Distraction technique is a psychological approach, which has interested the field of medicine. Aim(s): To review the effectiveness of Distraction techniques in Obstetrics and Gynaecology. Material(s) and Method(s): This systematic review study was conducted on articles indexed in Cochrane Library, Web of Sciences, PubMed, Scopus, Google Scholar, CINHAL and Persian databases including SID, Magiran, and Barakat Knowledge Network System in October 2018 without time restriction. Search was conducted according to MeSH-based keywords, including distraction or distraction technique Distraction OR Distraction techniques and use + or AND with keywords Midwife, Birth Attendants, Traditional Midwives, Traditional Birth Attendant, Genital Diseases, Female, Gynaecologic Surgical Procedures, Reproductive Medicine, Obstetrics, Pregnancy Complications, Obstetric Surgical Procedures, Gynaecology and Gynaecological diseases. To ensure, the search process was conducted once again by using keywords of dysmenorrhea, vomiting, nausea, pregnancy, delivery and cesarean section. The inclusion criteria, based on PICOS were: Clients of obstetrics-gynaecology centres; receiving a distraction technique; clinical trials with a parallel design; psychosomatic outcomes; full-text articles in Persian and English. Evaluation of the quality of articles was done using Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0. Result(s): Five out of 595 articles were included in this systematic review. Outcomes of these studies were intensity of pain, and stress and anxiety in patients visiting obstetrics-gynaecology centres. Results showed that the distraction techniques could reduce the intensity of pain in patients under obstetrics-gynaecology procedures, and also the stress of prepubescent girls caused by genital examination. Moreover, the meta-analysis results showed that the mean score of anxiety in pregnant women and women at labour, who received distraction interventions, was significantly lower than the control (mean difference: -7.0; 95% Confidence Interval: -13.7 to -0.4; p=0.04). Conclusion(s): According to the results, distraction is a simple, low-cost, and accessible technique for reducing pain, anxiety, and stress in the field of obstetrics and gynaecology. Moreover, given that there are scant studies into this field and their high risk of bias, it is recommended to use distraction techniques in different areas of clinical trials with higher quality.Copyright © 2019, Journal of Clinical and Diagnostic Research. All rights reserved.

Amjad, R., et al. (2024). "Hypofractionated Radiotherapy in Gynecologic Malignancies-A Peek into the Upcoming Evidence." Cancers 16(2).
	Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide.

Amrita, M., et al. (2022). "The impact of exercise on fertility in women with a healthy weight: a systematic review."
	
Amstad, G., et al. (2022). "Perioperative management with ferric carboxymaltose and tranexamic acid to reduce transfusion rate in gynaecological carcinoma surgery (TRANAFER-Study): study protocol for a single-blind, monocentre, randomised trial." BMJ Open 12(9): e057381.
	Introduction Radical abdominal surgery is part of the standard treatment for women with advanced gynaecological carcinoma. The surgery often leads to intraoperative blood loss frequently exceeding 1000 mL. Approximately 50% of women undergoing radical surgery require blood transfusions. Perioperative blood transfusions have been shown to increase the risk of postoperative complications, delayed wound healing, increased length of stay, increased postoperative morbidity and mortality. Previous studies have demonstrated an association between perioperative anaemia and surgical morbidity and mortality. By reducing transfusions and improving recovery from surgery, preoperative diagnostic and management of perioperative anaemia is a great opportunity to optimise postoperative patient outcome. Methods and analysis This is a single-blind, monocentre, randomised trial with four parallel groups (three therapeutic groups and one control group without treatment according to current standards of care) conducted in women undergoing radical gynaecological surgery. The primary study objective is to determine the effect of perioperative treatment with either intravenous iron, tranexamic acid or with a combination of both medicines on the reduction of intraoperative and postoperative red blood cell transfusions in gynaecological carcinoma patients. A total of N=126 women with gynaecological carcinoma will be recruited at the University Hospital Basel, Department of Gynaecology. Blood parameters will be measured at the recruitment, prior to surgery, 2 days after surgery and on the 21st-28th day after surgery. Recruitment started in August 2021. Ethics and dissemination The study will be performed according to the guidelines of the Declaration of Helsinki and is approved by the Ethics Committee for Northwest and Central Switzerland in Basel (EKNZ Protocol ID 2020-01194). The results of this study will be published and presented in various scientific forums. Trial registration number NCT03792464.Copyright ©

Amsterdam, U. M. C. and V. location (2021). The Effect of Dietary Interventions, or no Intervention, on Pain and Quality of Life in Women Diagnosed With Endometriosis.
	No Results Available Other: Low FODMAP diet|Other: Endometriosis diet pain scores|Quality of Life (QoL)|Gastro-Intestinal Health|Adhesion to dietary intervention Female Not Applicable 62 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care W20_534 # 20.593 December 31, 2022

Ana, D. n., et al. (2023). "Physiotherapy interventions in postpartum depression: a systematic review."
	
Ana, K., et al. (2023). "Intravaginal physical energy for treatment of genitourinary syndrome of menopause in breast cancer survivors: A systematic review and meta-analysis."
	
Ana, K., et al. (2023). "Efficacy of physiotherapy for treating vulvodynia: a systematic review and metanalysis." PROSPERO International prospective register of systematic reviews.
	
Ana, K., et al. (2022). "Physical energy for management of Genitourinary Syndrome of Menopause: A protocol for overview of systematic review and meta-analysis."
	
Ana Lívia, D., et al. (2022). "The impact of the Pilates Method as a treatment for pelvic floor disorders."
	
Ana, N., et al. (2023). "Dietary Approach to Premenstrual Syndrome Symptoms Alleviation – A Systematic Review."
	
Ana, R., et al. (2023). "Effect of Probiotics in Association with Antibiotics in Bacterial Vaginosis Compared to Treatment with Antibiotics Isolated: A Systematic Review."
	
Ana, R., et al. (2021). "Androgens and diminished ovarian reserve: The long road from basic science to clinical implementation. A comprehensive and systematic review with meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Anand, A., et al. (2023). "Stress urinary incontinence in females. Diagnosis and treatment modalities - past, present and the future." Journal of Clinical Urology 16(6): 622-630.
	Introduction: Stress urinary incontinence (SUI) can be defined as involuntary and unintentional loss of urine through the urethra when vesical pressure exceeds the urethral sphincter pressure during instances of coughing, sneezing or physical exercise. Stress urinary incontinence is the most common form of incontinence in females with an estimated prevalence of 4.5-53% in adult women with urinary incontinence. Yet despite its distressing nature and a negative impact on quality of life, very few women present with their symptoms to a urologist. Material(s) and Method(s): A literature search of the MEDLINE, Cochrane Library, Embase, NLH, ClinicalTrials.gov and Google Scholar databases was done up to November 2020, using terms related to SUI, medical therapy, surgical therapy and treatment options. The search terms included female stress urinary incontinence, mid-urethral sling, tension-free vaginal tape and trans obturator tape. The search included original articles, reviews and meta-analyses. Conclusion(s): Current guidelines for the management of stress urinary incontinence propose a step-ladder pattern, based on treatment invasiveness starting from conservative therapies, then drugs followed by minimally invasive procedures and culminating in invasive surgeries. The surgical approach is to be considered only after conservative therapies fail. The recent advances in the treatment of stress urinary incontinence have brought to light newer modalities and newer technologies that can be utilized which include laser therapy, stem cell therapy, intravesical balloon and others that show a lot of promise. This paper provides an in-depth analysis and reviews the literature on the current modalities and the future prospects of female stress urinary incontinence. Level of Evidence: Not applicable for this review article.Copyright © British Association of Urological Surgeons 2021.

Anastasia, V., et al. (2023). "Effect of extracorporeal shockwave therapy of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on the patient pain outcome scores."
	
Anastasio Mary, K., et al. (2023). "Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial." Obstetrics and Gynecology 142(6): 1459-1467.
	Objective: To investigate the efficacy of cryocompression therapy to prevent chemotherapy-induced peripheral neuropathy.; Methods: This single-institution, randomized, self-controlled trial of cryocompression enrolled gynecologic cancer patients planned for five to six cycles neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Participants were randomized to cryocompression on dominant versus non-dominant hand and foot (treatment), with no intervention on the opposite side (control). Compression socks and gloves and ice bags were applied 15 minutes before, during, and 15 minutes after infusion. Primary outcome measures included the PNQ (Patient Neurotoxicity Questionnaire) and the Semmes-Weinstein monofilament test; secondary outcomes included the FACT/GOG-NTX (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) and patient acceptability and tolerability. Sixty patients completing the study were necessary to detect a 70% reduction in the odds of PNQ grade C or higher peripheral sensory neuropathy with 80% power.; Results: Ninety-one patients were enrolled from January 2021 to October 2022; 69 were eligible for final analysis. Of the 91 patients, 64.8% were White, 30.8% were Black, and 1.1% were Hispanic or Latina. With successive cycles, more patients had sensory PNQ grade C or higher neuropathy on the control side compared with the cryocompression side. Cryocompression decreased the odds of sensory neuropathy (PNQ grade C or higher) by 46% at final visit (odds ratio 0.54, 95% CI 0.31-0.94; P =.03). There was no difference in tactile sensitivity based on the monofilament test between sides at the final visit. At the final visit, average FACT/GOG-NTX-11 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 11 Item Version) scores were significantly lower on the cryocompression than the control side (estimate -0.97, 95% CI -1.89 to -0.06; P =.04), as were FACT/GOG-NTX-4 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version) scores (estimate -0.35, 95% CI -0.64 to -0.05; P =.02). More than 85% of patients assessed the intervention as acceptable and tolerable.; Conclusions: Cryocompression therapy reduces subjective chemotherapy-induced peripheral sensory neuropathy in patients who are receiving paclitaxel or cisplatin for gynecologic cancer.; Clinical Trial Registration: ClinicalTrials.gov , NCT04563130.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Anastasiou, E., et al. (2022). "The relationship between hormonal contraception and cervical dysplasia/cancer controlling for human papillomavirus infection: A systematic review." Contraception 107: 1-9.
	Objective: Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection.; Study Design: Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725).; Results: Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association.; Conclusion: We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk.; Implications: Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Anaya, Y., et al. (2022). "Triggering with 1,500 IU of human chorionic gonadotropin plus follicle-stimulating hormone compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial." Fertility and Sterility 118(2): 266-278.
	Objective: To assess if triggering with 1,500 IU of human chorionic gonadotropin (hCG) with 450 IU of follicle-stimulating hormone (FSH) induces noninferior oocyte competence to a standard dose of hCG trigger used in in vitro fertilization (IVF). The alternative trigger will be considered noninferior if it is at least 80% effective in promoting oocyte competence. Design(s): Randomized, double-blinded, controlled noninferiority trial. Setting(s): Academic infertility practice. Patient(s): Women aged 18-41 undergoing IVF with antral follicle count >=8, body mass index <=30 kg/m2, and no history of >=2 IVF cycles canceled for poor response were enrolled. Participants with a serum estradiol >5,000 pg/mL on the day of trigger were excluded because of high risk of ovarian hyperstimulation syndrome. Intervention(s): Participants were randomized to receive an alternative trigger of 1,500 IU of hCG plus 450 IU of FSH or a standard trigger dose of hCG (5,000 or 10,000 IU) for final oocyte maturation. Main Outcome Measure(s): The primary outcome was total competent proportion, defined as the probability of 2 pronuclei from an oocyte retrieved. The alternative trigger will be considered noninferior to the standard trigger if a 1-sided 95% confidence interval (CI) of the relative risk (RR) is not <0.8. Secondary outcomes included oocyte recovery and maturity, intracytoplasmic sperm injection fertilization, embryo quality, pregnancy rates, as well as serum and follicular hormones. Secondary outcomes were compared using a 2-sided superiority test. Outcomes were analyzed by intention-to-treat and per-protocol. Result(s): A total of 105 women undergoing IVF were randomized from May 2015 to June 2018. The probability of the primary outcome was 0.59 with the alternative trigger and 0.65 with the standard trigger, with a RR of 0.91 and a 1-sided 95% CI of 0.83. Noninferiority of the alternative trigger was demonstrated. Live birthrate from all fresh transfers in the alternative trigger group vs. standard trigger was 46.9 vs. 46.4% (RR, 1.01; 95% CI, 0.62-1.62), respectively. Live birthrate per randomized participant was 48.1% in the alternative trigger group vs. 62.7% with the standard trigger (RR, 0.73; 95% CI, 0.48-1.11). No participants had a failed retrieval. Conclusion(s): Triggering with 1,500 IU of hCG plus 450 IU of FSH promoted noninferior oocyte competence compared to a standard hCG trigger dose. Trial registration: NCT02310919.Copyright © 2022

Andebrhan Sarah, B., et al. (2023). "Pelvic organ prolapse recurrence after pregnancy following uterine-sparing prolapse repair: a systematic review and meta-analysis." International Urogynecology Journal 34(2): 345-356.
	Introduction: We sought to determine rates of pelvic organ prolapse (POP) recurrence following pregnancy and delivery in reproductive-age women with prior hysteropexy.; Methods: Scopus, MEDLine, EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched from inception to May 2020 for combinations of any of the keywords: "pregnancy", "delivery", "fertility", or "cesarean" with a comprehensive list of uterine-sparing surgical procedures for POP repair. Using approach, 1,817 articles were identified describing surgical, uterine-sparing POP repair techniques and subsequent pregnancy and delivery outcomes in reproductive-age women. RESULTS: Twenty-seven studies describing 218 pregnancies, including 215 deliveries and 3 abortions, were summarized using narrative review and descriptive statistics. Successful pregnancies were reported following a diverse range of uterine-sparing prolapse repairs, both native tissue and mesh-augmented, that utilized vaginal, open abdominal, and laparoscopic approaches. We observed shifts from native tissue repairs to mesh-augmented laparoscopic repairs over time. POP recurrence occurred in 12% of subjects overall, 15% after vaginal and 10% after abdominal prolapse repairs. While meta-analysis identified higher recurrence rates after vaginal delivery (15%) than cesarean section (10%), due to small study numbers, multiple confounders, and heterogeneity between studies, no significant differences in recurrence rates could be identified between vaginal and abdominal surgical approaches, utilization of mesh augmentation, or mode of delivery.; Conclusion: Although literature on pregnancy following uterine-sparing POP repair is limited, available data suggest that prolapse recurrence after pregnancy and delivery remains similar to that after prolapse repair without subsequent pregnancies with few documented perinatal complications.; Systematic Review Registration: PROSPERO, CRD42021247722. (© 2022. The International Urogynecological Association.)

Andes, A., et al. (2022). "Does the real-world match the randomized trial? Reach and effectiveness of a community-based incontinence program." International Urogynecology Journal 33: S36.
	Introduction: Mind Over Matter: Healthy Bowels, Healthy Bladder (MOM) is a month‐long, small‐group (8‐12 women) behavior change intervention implemented by trained facilitators in community settings. In a 2017 randomized, controlled trial (RCT) MOM significantly improved urinary incontinence (UI) in older women and increased the proportion of participants doing pelvic floor muscle (Kegel) exercises consistently. Objective: In this program evaluation, we sought to describe the impact of MOM when implemented in the real world, delivered by community organizations serving older women, and compare its impact to that seen in the RCT. Methods: We analyzed program evaluation data from 295 women who attended 29 MOM workshops between March 1, 2019 and March 31, 2020 and data collected from the treatment arm inMOM's RCT (N=62). Women completed brief questionnaires at baseline (before their first MOM session) and at MOM completion (following the last MOM session). Participants completed the International Consultation on Incontinence Questionnaire (ICIQ‐UI) and Vaizey/St. Mark's at baseline (before their first MOM session) and at MOM completion (following the last MOM session) and provided information about their frequency of certain behaviors.Whereas RCT participants completed the patient global impression of improvement (PGI‐I) 3 months following MOM completion, community participants completed the global perception of improvement (GPI) immediately following MOM completion. Women in the RCT who reported improved PGI‐I for UI or FI were categorized as perceiving improvement for the purpose of this analysis. Descriptive analyses compared behaviors and symptoms before and after MOM among participants in both settings, with p‐value less than .05 as significant. Results: Community and RCT participants had similar mean ages (74+/‐ 8 and 75+/‐8) but RCT participants were more likely to live in rural areas (29% versus 23%) and had higher baseline incontinence severity. Mean number of participants per MOM workshop was 10 in both settings. Among community participants, 91% (212/232) had UI and 44% (77/ 175) had FI at baseline. The vast majority of participants in MOM in the community [90% (170/189)] and in the RCT [85% (50/59)] perceived incontinence symptoms to be improved following the MOM program. Details about changes in behaviors and symptoms from baseline toMOM completion are outlined in the table. Among both RCT and community participants, the proportion of women doing Kegels consistently increased significantly following MOM completion; the proportion of women experiencing stress UI decreased, and modest improvements were seen in ICIQ‐UI scores. The number of mean pads used per 24 hours increased slightly among RCT participants and decreased among community participants. There were no statistically significant differences in care‐seeking plans or FI severity as measured by the Vaizey / St. Marks. Conclusions: Community implementation of MOM reached similar women and achieved similar results to those seen in the RCT. The magnitude of symptom improvement was lower in the real world, possibly related to lower baseline symptom severity. Given these subtle differences, continued evaluation of intervention impact in real‐world implementation settings remains critical.

André, T., et al. (2023). "Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial." JAMA Network Open 6(11): e2341165.
	Importance: Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor.; Objective: To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors.; Design, Setting, and Participants: The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017. Participants had advanced or recurrent dMMR and microsatellite instability-high (MSI-H) or polymerase epsilon (POLE)-altered solid tumors. The data cut for this interim analysis was from November 1, 2021, with median follow-up of 27.7 months.; Interventions: Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal.; Main Outcomes and Measures: The primary objective was to evaluate objective response rate and duration of response in patients with dMMR solid tumors by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1.; Results: The efficacy population included 327 patients (median [range] age, 63 [24-85] years; 235 [71.9%] female; 7 [2.1%] Asian, 6 [1.8%] Black, and 206 [63.0%] White patients), with 141 patients (43.1%) with dMMR endometrial cancer, 105 patients (32.1%) with dMMR colorectal cancer, and 81 patients (24.8%) with other dMMR tumor types. All patients had at least 1 previous line of therapy. Objective response rate assessed per blinded independent central review for dMMR solid tumors was 44.0% (95% CI, 38.6% to 49.6%). Median duration of response was not reached (range, ≥1.18 to ≥47.21 months); 72.2% of responders (104 of 144) had a response lasting 12 or more months. Median progression-free survival was 6.9 months (95% CI, 4.2 to 13.6 months); probability of progression-free survival at 24 months was 40.6% (95% CI, 35.0% to 46.1%). Median overall survival was not reached (95% CI, 31.6 months to not reached). The most frequent immune-related adverse events were hypothyroidism (25 [6.9%]), alanine aminotransferase increase (21 [5.8%]), and arthralgia (17 [4.7%]). No new safety concerns were identified.; Conclusions and Relevance: In this nonrandomized controlled trial, dostarlimab was a well-tolerated treatment option with rapid, robust, and durable antitumor activity in patients with diverse dMMR solid tumors. These findings suggest that dostarlimab provides meaningful long-term benefit in a population with high unmet need.; Trial Registration: ClinicalTrials.gov Identifier: NCT02715284.

Andressa, S., et al. (2023). "Electrotherapy and manual therapy for chronic pelvic pain syndrome: systematic review with meta-analysis."
	
Andrews, R., et al. (2023). "The health &her app is associated with improved symptom outcomes among 1,900 menopausal women." Post Reproductive Health 29(3): 174-175.
	Objective: Symptom monitoring is associated with improvements in menopausal symptoms (Andrews et al., 2021; 2023). The Health &Her app enables menopausal women to monitor their symptoms, symptom triggers, and menstrual periods, and enables them to engage in a variety of digital activities designed to promote health and wellbeing. The aim of the present study was to examine whether sustained weekly engagement with the app is associated with improvements in menopausal symptoms. Method(s): This quasi-experimental study analysed data provided by 1,900 Health &Her app users across a 2-month period. Symptom change from baseline, over the 2-month period, was the outcome measure. A linear mixed effects model explored whether app engagement was predictive of symptom reductions. Secondary hypotheses assessed whether app-usage factors such as total number of days spent monitoring symptoms and symptom triggers, reporting menstrual periods, and using in-app activities were independently predictive of symptom changes from baseline. Covariates included hormone replacement therapy 174 Post Reproductive Health 29(3) (HRT) use, hormonal contraceptive use, present comorbidities, age, and dietary supplement use. To examine whether symptom types had varying impacts on symptom changes, symptom scores at baseline were evaluated and split according to specific symptom domains (i.e. psychological, urogenital, vasomotor, and physical). Result(s): Nine weeks of app engagement had the largest impact on symptom reductions: b =-4.0 [-5.8,-2.3] compared to 8 weeks: b =-3.8 [-5.2,-2.3], 7 weeks: b =-3.2 [-4.5,-1.8], 6 weeks: b =-3.3 [-4.5,-2.0], 5 weeks: b =-2.6 [-3.7,-1.5], 4 weeks: b =-2.7 [-3.8,-1.6], and 3 weeks: b =-1.2, 95% CI [-2.2,-0.26]. Monitoring symptoms, daily use of in-app activities, and logging menstrual periods were each independently associated with symptom reductions. Of the four symptom domains assessed, reporting psychological symptoms at baseline was associated with the greatest reductions in total symptom scores: b=-0.54 [-0.62,-0.46]. Conclusion(s): This study demonstrated that greater weekly engagement with the app was associated with greater reductions in symptoms over a 2-month period. It is recommended that women be made aware of menopausespecific apps in primary care settings, such as that provided by Health &Her, to support them to manage their menopausal symptoms and track the efficacy of menopausespecific treatments.

Andrews Robin, A. F., et al. (2023). "Symptom monitoring improves physical and emotional outcomes during menopause: a randomized controlled trial." Menopause (New York, N.Y.) 30(3): 267-274.
	Abstract: Objectives: A recent systematic review suggested that symptom monitoring can result in reductions in menopausal symptoms and improvements in health-related behaviors. To date, no studies have experimentally investigated whether symptom monitoring could be a beneficial intervention during the menopause transition.Methods: One hundred perimenopausal and postmenopausal women (mean age, 46 y; SD, 8 y) were randomized into either a monitoring-intervention or control group. A mixed between/within design was used, with group membership (ie, monitoring-intervention or control) as the between-subjects component and time (ie, baseline and 2-wk follow-up) as the within-subjects component. Dependent variables included symptom reductions and emotional reactions as measured via the Daily Record Keeping form. Secondary outcomes included help-seeking, communication, medical decision making, health awareness, self-efficacy, and health anxiety.Results: A linear mixed-effects model demonstrated that the monitoring-intervention group reported a 42% reduction in physical symptoms at follow-up versus a 12% reduction in the control group: ρ = 0.009, β = 6.3, 95% CI (1.5-11). Negative emotions also significantly reduced in the monitoring-intervention group but did not alter in the control group: ρ < 0.001, β = 3.4, and 95% CI (1.6-5.2). These effects remained significant after controlling for potential moderator variables such as trait neuroticism and coping preferences and potential confounders such as medical and demographic characteristics. Variances in other health outcomes were nonsignificant.Conclusions: Findings demonstrated that symptom monitoring reduced symptoms and negative emotions within a perimenopausal and postmenopausal sample, and these outcomes endured after controlling for key moderators and covariates. However, symptom monitoring was not related to improvements in health-related behavioral outcomes, which contrasts with previous findings. These findings show that symptom monitoring may be useful within healthcare settings by providing perimenopausal and postmenopausal women with a simple and accessible means of symptom alleviation while they await treatment or medical consultation.; Competing Interests: Financial disclosure/conflicts of interest: R.A.F.A. is currently employed by Health & Her. D.L. has received honoraria and expenses from Gedeon Richter: Preglem for expert speaker and web contributions. B.J. has no conflicts of interest to declare. (Copyright © 2023 by The North American Menopause Society.)

Andriani, L., et al. (2023). "Telehealth utilization in gynecologic oncology clinical trials." Gynecologic Oncology 177: 103-108.
	Objective: Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were underutilized in gynecologic oncology clinical trials. Current literature on these operational changes provides anecdotal experience and expert opinion with few studies describing patient-level safety data. We aimed to evaluate the safety and feasibility of telehealth and remote clinical trial operations during the COVID-19 Pandemic. Method(s): Gynecologic oncology patients enrolled and actively receiving treatment on a clinical trial at a single, academic institution during the designated pre-Telehealth and Telehealth periods were identified. Patients with at least 1 provider or research coordinator telehealth visit were included. Patient demographics, health system encounters, adverse events, and protocol deviations were collected. Pairwise comparisons were performed between the pre-Telehealth and Telehealth period with each patient serving as their own control. Result(s): Thirty-one patients met inclusion criteria. Virtual provider visits and off-site laboratory testing increased during the Telehealth period. Delays in provider visits, imaging, and laboratory testing did not differ between time periods. Total and minor protocol deviations increased in incidence during the Telehealth period and were due to documentation of telehealth and deferment of non-therapeutic testing. Major protocol deviations, emergency department visits, admissions, and severe adverse events were of low incidence and did not differ between time periods. Conclusion(s): Telehealth and remote clinical trial operations appeared safe and did not compromise clinical trial protocols in a small, single institutional study. Larger scale evaluations of such trial adaptations should be performed to determine continued utility following the Pandemic.Copyright © 2023

Andrielle, L., et al. (2021). "Effect of Physiotherapeutic Interventions on Chronic Pelvic Pain in Women: Systematic Review with Metanalysis."
	
Andring Lauren, M., et al. (2023). "Patient Reported Outcomes for Women Undergoing Definitive Chemoradiation for Gynecologic Cancer: A Prospective Clinical Trial." Practical radiation oncology 13(6): e538-e546.
	Purpose: Patients with gynecologic malignancies have high psychosocial and symptom burden. We report data from a prospective trial evaluating patient-reported outcome (PRO) metrics in women undergoing definitive chemoradiation with brachytherapy (BT).; Methods and Materials: A single-institution prospective trial evaluating outcomes of gynecologic cancer patients undergoing BT. Questionnaires to assess PROs at baseline, post-BT, and 60-day follow-up were collected, using European Organization for Research and Treatment of Cancer-Quality of Life Question-Core 30 and European Organization for Research and Treatment of Cancer-Quality of Life Question-Cervical Cancer Module validated metrics. Higher scores for functional scales/global health and lower scores for symptom items are favorable. European Organization for Research and Treatment of Cancer-Quality of Life Question-Core 30 mean scores were compared with a reference population. When comparing the study population between time points, medians, interquartile range, and nonparametric testing were used.; Results: Thirty-three patients were enrolled, and 29 (88%) completed baseline PRO metrics. Mean global health score was worse than the reference population of women with any cancer diagnosis at baseline (41 vs 59, P < .001) and decreased further at follow-up (42 vs 33, P = .005). Compared with the cervical cancer reference, our patients had significantly worse social function (62 vs 83, P = .03), financial toxicity (49 vs 10, P < .001), fatigue (49 vs 34, P = .04), nausea/vomiting (26 vs 9, P = .001), and appetite loss (36 vs 16, P = .004).The majority of patients described depression (53%), feeling less attractive (64%), life interference (66%), and/or worry (69%). At baseline, higher global health scores were associated with improved physical functioning (R 2 0.58, P < .001), social functioning (R 2 0.56, P < .001), and body image (R 2 0.40, P < .001); lower scores with more symptom burden (R 2 0.71, P < .001), financial toxicity (R 2 0.50, P < .001), and/or sexual worry (R 2 0.25, P = .001).; Conclusions: Patients with cervical cancer have significant symptom burden and psychosocial toxicity, contributing to decreased quality of life. These data highlight the need for improved support throughout treatment for this high-risk population.; Competing Interests: Disclosures None. (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Ang, X. Y., et al. (2022). "Lactobacilli reduce recurrences of vaginal candidiasis in pregnant women: a randomized, double-blind, placebo-controlled study." Journal of applied microbiology 132(4): 3168-3180.
	Aims: The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; placebo, n = 39) and the potential benefits on quality of life.; Methods and Results: The lactobacilli putative probiotic (SynForU-HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8-weeks in a randomized, double-blind, placebo-controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week-4 and week-8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week-4 and continued after week-8 (P < 0·05), accompanied by reduced symptoms for burning after week-8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week-4 (P = 0·010) and continued after week-8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week-8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week-4 and week-8 (P < 0·05). Patients consuming lactobacilli showed higher defecation times per week at week-4 (P = 0·010) and week-8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy-induced constipation.; Conclusions: Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC.; Significance and Impact of the Study: The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy. (© 2021 The Society for Applied Microbiology.)

Angela, F. and B. Hayley (2022). "A systematic review of community pharmacy interventions to improve peri- and post-menopausal health."
	
Anglès-Acedo, S., et al. (2021). "Sexual activity and function in women with advanced stages of pelvic organ prolapse, before and after laparoscopic or vaginal mesh surgery." International Urogynecology Journal 32(5): 1157-1168.
	INTRODUCTION AND HYPOTHESIS: The differential impact of specific pelvic organ prolapse (POP) surgery on sexual activity and function is unknown. Our primary aim was to analyse sexual inactivity and function in women with symptomatic advanced stages of POP and the changes incurred after laparoscopic or vaginal mesh surgery. METHODS: We performed a secondary analysis of sexual outcomes of a previously published randomised controlled trial comparing laparoscopic sacrocolpopexy/cervicopexy (LSC-Cx) and anterior vaginal mesh (AVM) in 120 women (60/group) with symptomatic anterior POP stage ≥ 3 and apical ≥ 2. Sexual activity and function were assessed preoperatively and 1 and 2 years postoperatively using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA-Revised (PISQ-IR). RESULTS: Sexual activity was recovered in 42.9% of non-sexually active (NSA) women 1 year postoperatively, mainly in women with higher preoperative POP-related subscale scores of the PISQ-IR, which indicated a negative preoperative sexuality by POP. Recovery of sexual activity was greater after LSC-Cx, albeit not significantly (2 years: 35.5% AVM vs. 45% LSC-Cx). Among sexually active (SA) women preoperatively remaining SA postoperatively, the difference in the mean PISQ-IR summary score significantly improved [mean baseline difference - 2 years; all: 0.3 (95% CI 0.1 to 0.5) p = 0.001; AVM 0.19 (95% CI -0.1 to -0.5) p > 0.05; LSC-Cx 0.37 (95% CI 0.1 to 0.7) p = 0.003]. Preoperative dyspareunia was significantly reduced after LSC-Cx (baseline: 24.6%, 2 years: 9.8%, p = 0.0448), but not after AVM (baseline: 20.7%, 2 years: 18.2%, p = 0.7385). CONCLUSIONS: Most women reported improved sexual activity and function 2 years after LSC-Cx or AVM, mainly because of enhanced POP-related subscales in both NSA and SA women. Recovery of sexual activity and improved sexual function were greater after LSC-Cx compared to AVM, likely related to less postoperative dyspareunia.

Anglim, B., et al. (2022). "The effect of local estrogen therapy on the urinary microbiome composition of postmenopausal women with and without recurrent urinary tract infections." International Urogynecology Journal 33(8): 2107-2117.
	Introduction and Hypothesis: Recurrent urinary tract infections (rUTIs) occur in 2-10% of postmenopausal women. Local estrogen therapy (LET) has been shown to reduce UTIs. This study aimed to compare the urinary microbiome between patients with and without a history of rUTIs and to examine whether treatment with LET influences the diversity and richness of microbiome species in two groups.; Methods: Postmenopausal women with and without rUTIs attending the urogynecology clinic between April 2019 and December 2020 were recruited. Participant baseline characteristics and demographics were recorded. Aseptic transurethral urine samples were collected at recruitment and at 3-6 months following treatment with LET. The V1-V2 and ITS regions of the 16S rRNA gene were sequenced to identify bacteria.; Results: A total of 37 women were recruited, 20 controls and 17 patients with rUTI. During follow-up, symptomatic UTIs occurred in 3/17 (17.6%) and 0/20 in the rUTI group and control group, respectively. Klebsiella aerogenes was present in 80% of rUTI samples and in 53.3% of control samples before LET. Abundance of Finegoldia magna was present in 33.3% of samples before LET, but only in 6.7% after LET. There was no change in relative abundance of lactobacillus species following LET in both groups.; Conclusions: Treatment with vaginal LET altered the local hormonal environment of the urinary bladder and likely protected women from development of rUTI by decreasing the presence of F. magna. To confirm the significance of this bacterial species in rUTI symptomatology, our finding needs to be validated on a larger patient cohort. (© 2021. The International Urogynecological Association.)

Angoorani, P., et al. (2023). "The effects of probiotics, prebiotics, and synbiotics on polycystic ovarian syndrome: an overview of systematic reviews." Frontiers in Medicine 10: 1141355.
	Introduction: Accumulating evidence has highlighted the critical role of the gut microbiota and its potential action as a regulator of metabolic disorders including insulin resistance, obesity, and systemic inflammation in polycystic ovarian syndrome (PCOS). Microbiota-modulating interventions, such as probiotics, prebiotics, and synbiotics, could be effective in PCOS management.; Methods: We conducted an overview of systematic reviews (SRs) and meta-analyses to summarize reviews regarding the effectiveness of probiotics/prebiotics/synbiotics on the management of PCOS through a systematic literature search in PubMed, Web of Science, and Scopus databases until September 2021.; Results: Eight SRs and meta-analyses were included in this study. Our overview confirmed that probiotic supplementation had a potentially beneficial effect on some PCOS-related parameters including body mass index (BMI), fasting plasma glucose (FPG), and lipid profiles. Evidence shows that synbiotics in comparison with probiotics were less effective on these parameters. The methodological quality of SRs was assessed using the AMSTAR-2 assessment tool and was determined as high for four SRs, low for two SRs, and critically low for one SR. Due to limited evidence and high heterogeneity of the studies, it remains difficult to identify optimal probiotics strains, prebiotics types, length of duration, and doses.; Discussion: Future clinical trials with higher quality are recommended to clarify the efficacy of probiotics/prebiotics/synbiotics on the management of PCOS and provide more accurate evidence.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Angoorani, Ejtahed, Ettehad Marvasti, Taghavi, Mohammadpour Ahranjani, Hasani-Ranjbar and Larijani.)

Anindita, A., et al. (2022). "Effectivity of Isoflavones in the Treatment of Postmenopausal Symptoms : Systematic Review and Meta-Analysis."
	
Anita, V. and S. Vartika (2021). "Effect of yoga therapy on health outcomes in women with polycystic ovary syndrome: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Anitua, E., et al. (2023). "Efficacy of Platelet-Rich Plasma in Women with a History of Embryo Transfer Failure: A Systematic Review and Meta-Analysis with Trial Sequential Analysis." Bioengineering (Basel, Switzerland) 10(3).
	Assisted reproductive technology (ART) is used to enhance pregnancy in infertile women. In this technique, the eggs are removed from the ovary and fertilized and injected with sperm to make embryos. Unfortunately, embryo implantation failures still occur in many of these women. Platelet-rich plasma (PRP) therapies use a patient's own platelets to promote tissue healing and growth, including endometrium. The growth factors provided by the platelets play a criterial role on the regenerative ability of PRP. In the last years, PRP treatments have been gaining a lot of popularity to treat women with repeated ART failures. In this study, we collected and summarized all information published in the scientific literature to assess the evidence of the PRP effect on pregnancy. We only considered randomized controlled trials (RCT), a type of study designed to be unbiased and considered at the highest level of evidence. Our analysis indicates that PRP therapies might be an effective treatment in cases of poor responsiveness to conventional ART. However, additional studies (well-designed) are necessary to confirm this beneficial effect of PRP.

Anitua Fundación, E. (2022). Plasma Rich in Growth Factors (PRGF) for the Treatment of Lichen Sclerosus Atrophicus of the Vulva.
	No Results Available Drug: PRGF|Drug: Clobetasol Propionate Evolution of quality of life measured by Skindex-29 index|Evolution of response to treatment at 1, 3, 6 and 8 months through the clinical scale of vulvar lichen sclerosus (CSS)|Evolution of pain at 1, 3, 6 and 8 months measured through the visual analog pain scale (VAS)|Evolution of the improvement at 1, 3, 6 and 8 months through the patient's global impression (PGI-I)|Evolution of clinical improvement at 1, 3, 6 and 8 months through the investigator's global assessment (IGA)|Frequency of recurrences at 6 and 8 months of treatment|Frequency of complications|Platelet concentration|Platelet recovery|Presence of leukocyte Female Phase 3 30 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment BTIIMD-01-EC/217LIQUEN October 2023

Anna, E., et al. (2022). "Effects of different dietary approaches in women with polycystic ovary syndrome: a systematic review and network meta-analysis."
	
Anna, K., et al. (2022). "Efficacy of bladder training in adults with overactive bladder syndrome: a systematic review."
	
Annelotte, v., et al. (2022). "Virtual Reality as pain and anxiety management in gynecological procedures: a systematic review."
	
Anneveldt, K. J., et al. (2022). "Increased MR-guided high intensity focused ultrasound (MR-HIFU) sonication efficiency of uterine fibroids after carbetocin administration." European Journal of Radiology Open 9: 100413.
	Purpose: We investigated whether administration of the long-acting uterus stimulant carbetocin increased intra-subject sonication efficiency during Magnetic Resonance image guided High Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids. Method(s): In this prospective cohort study, thirty women with symptomatic uterine fibroids undergoing MR-HIFU treatment were included between January 2018 and January 2019. Treatment started with three sonications on one side of the uterine fibroid. Subsequently, one ampoule of 1 mL carbetocin (100 microg/mL) was administered intravenously and treatment continued with three sonications on the other side of the uterine fibroid. We compared the intra-subject sonication efficiency, in terms of Energy Efficiency Factor (EEF), thermal dose volume and sonication time to ablate one cm3 of fibroid tissue, before and after carbetocin administration. Adverse events that occurred within 30 min after carbetocin administration were recorded. Result(s): Sonication efficiency improved after carbetocin administration as indicated by a significant decrease in EEF and sonication time (p = 0.006 and p = 0.001 respectively), and a significant increase in thermal dose volume reached (p = <0.001). Five women (16.7%) experienced temporary tachycardia, one women in combination with headache, within 30 min after carbetocin administration. Conclusion(s): Administration of the long-acting uterus stimulant carbetocin improved the MR-HIFU treatment intra-subject sonication efficiency in women with symptomatic uterine fibroids.Copyright © 2022 The Authors

Ann-Sophie, P., et al. (2021). "Efficacy and safety of the cervicosacropexy (CESA) vaginosacropexy (VASA) surgical procedure as treatment for pelvic organ prolapse and urinary incontinence: protocol for a systematic review (and meta-analysis)." PROSPERO International prospective register of systematic reviews.
	
Ansaari, N., et al. (2024). "Efficacy of in-person versus digital mental health interventions for postpartum depression: meta-analysis of randomized controlled trials." Journal of Reproductive and Infant Psychology.
	Aim: This meta-analysis aimed to compare the efficacy of in-person and digital mental health interventions in addressing Postpartum Depression. Method(s): Following PRISMA guidelines, the protocol for this meta-analysis was registered at the Open Science Framework (Retrieved from osf.io/wy3s4). This meta analysis included Randomized Controlled Trials (RCTs) conducted between 2013 and 2023. A comprehensive literature search identified 35 eligible RCTs from various electronic databases. Inclusion criteria focused on pregnant women over 18 years old, encompassing antenatal depression and up to two years postpartum. Diagnostic interviews or Edinburgh Postnatal Depression Scale (EPDS) were used to establish PPD. Digital interventions included telephonic, app-based, or internet-based approaches, while in-person interventions involved face-to-face sessions. Result(s): The meta-analysis revealed a moderate overall effect size of -0.69, indicating that psychological interventions are effective for PPD. Digital interventions (g = -0.86) exhibited a higher mean effect size than in-person interventions (g = -0.55). Both types of interventions displayed substantial heterogeneity (digital: I2 = 99%, in-person: I2 = 92%), suggesting variability in intervention content, delivery methods, and participant characteristics. Conclusion(s): Digital mental health interventions show promise in addressing PPD symptoms, with a potentially greater effect size compared to in-person interventions. However, the high heterogeneity observed in both modalities underscores the need for further research to identify key drivers of success and tailor interventions to diverse populations. Additionally, the choice between digital and in-person interventions should consider individual needs and preferences. Ongoing research should further investigate and optimise intervention modalities to better serve pregnant women at risk of PPD.Copyright © 2024 Society for Reproductive & Infant Psychology.

Ansari, A., et al. (2023). "Lactobacillus Probiotics Improve Vaginal Dysbiosis in Asymptomatic Women." Nutrients 15(8).
	Vaginal dysbiosis can lead to serious infections in asymptomatic women. Lactobacillus probiotics (LBPs) are being investigated as a promising therapy for reversing vaginal microbiota dysbiosis. This study aimed to investigate whether administering LBPs could improve vaginal dysbiosis and facilitate the colonization of Lactobacillus species in asymptomatic women. 36 asymptomatic women were classified based on the Nugent score as Low-NS (n = 26) and High-NS (n = 10) groups. A combination of Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, and Lactobacillus reuteri CBT LU4 was administered orally for 6 weeks. The study found that among women with a High-NS, 60% showed improved vaginal dysbiosis with a Low-NS after LBP intake, while four retained a High-NS. Among women with a Low-NS, 11.5 % switched to a High-NS. Genera associated with vaginal dysbiosis were positively correlated with the alpha diversity or NS, while a negative correlation was observed between Lactobacillus and the alpha diversity and with the NS. Vaginal dysbiosis in asymptomatic women with an HNS improved after 6 weeks of LBP intake, and qRT-PCR revealed the colonization of Lactobacillus spp. in the vagina. These results suggested that oral administration of this LBP could improve vaginal health in asymptomatic women with an HNS.

Antill, Y., et al. (2022). "Mismatch repair and clinical response to immune checkpoint inhibitors in endometrial cancer." Cancer 128(6): 1157-1161.
	Lay Summary: Endometrial cancer is common, and a subset recurs and requires additional treatment. Some of these are recognized as being susceptible to immune therapies and are said to have mismatch repair deficiency (dMMR). However, this clinical trial highlights which cases are more likely to respond well: those containing mutations in genes known as Lynch genes and also some with mutations in POLE/POLD1 ("ultra-hypermutation" genes). In contrast, the majority of dMMR endometrial cancers have silencing or DNA methylation of one of these genes, MLH1, and do not seem to be as responsive to single-agent immune therapy. The availability of combination therapies may be important to consider for these women. (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Antill, Y., et al. (2021). "Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial." Journal for Immunotherapy of Cancer 9(6): 002255.
	Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC) - mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR). Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics. Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1-2. Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR. Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129.Copyright ©

Antonio, S., et al. (2022). "Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome: a systematic review about diagnosis and surgical management."
	
Antonio, S., et al. (2023). "Use of letrozole as treatment for ectopic pregnancy: a systematic review and meta-analysis."
	
Antonios, S. and P. Nikolaos (2023). "Endometrial injury during hysteroscopy in women undergoing in vitro fertilization treatment. A systematic review and meta-analysis."
	
Antosh Danielle, D., et al. (2021). "Sexual function after pelvic organ prolapse surgery: a systematic review comparing different approaches to pelvic floor repair." American Journal of Obstetrics and Gynecology 225(5): 475.e471-475.e419.
	Objective: Women consider preservation of sexual activity and improvement of sexual function as important goals after pelvic organ prolapse surgery. This systematic review aimed to compare sexual activity and function before and after prolapse surgery among specific approaches to pelvic organ prolapse surgery including native tissue repairs, transvaginal synthetic mesh, biologic grafts, and sacrocolpopexy.; Data Sources: MEDLINE, Embase, and ClinicalTrials.gov databases were searched from inception to March 2021.; Study Eligibility Criteria: Prospective comparative cohort and randomized studies of pelvic organ prolapse surgeries were included that reported the following specific sexual function outcomes: baseline and postoperative sexual activity, dyspareunia, and validated sexual function questionnaire scores. Notably, the following 4 comparisons were made: transvaginal synthetic mesh vs native tissue repairs, sacrocolpopexy vs native tissue repairs, transvaginal synthetic mesh vs sacrocolpopexy, and biologic graft vs native tissue repairs.; Methods: Studies were double screened for inclusion and extracted for population characteristics, sexual function outcomes, and methodological quality. Evidence profiles were generated for each surgery comparison by grading quality of evidence for each outcome across studies using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.; Results: Screening of 3651 abstracts was performed and identified 77 original studies. The overall quality of evidence was moderate to high. There were 26 studies comparing transvaginal synthetic mesh with native tissue repairs, 5 comparing sacrocolpopexy with native tissue repairs, 5 comparing transvaginal synthetic mesh with sacrocolpopexy, and 7 comparing biologic graft with native tissue repairs. For transvaginal synthetic mesh vs native tissue repairs, no statistical differences were found in baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, persistent dyspareunia, and de novo dyspareunia. Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form change scores were not different between transvaginal synthetic mesh and native tissue repairs (net difference, -0.3; 95% confidence interval, -1.4 to 0.8). For sacrocolpopexy vs native tissue repairs, baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, de novo dyspareunia, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form score differences were not different. For biologic graft vs native tissue repairs, baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form changes were also not different. For transvaginal synthetic mesh vs sacrocolpopexy, there was no difference in sexual activity and sexual function score change. Based on 2 studies, postoperative total dyspareunia was more common in transvaginal synthetic mesh than sacrocolpopexy (27.5% vs 12.2%; odds ratio, 2.72; 95% confidence interval, 1.33-5.58). The prevalence of postoperative dyspareunia was lower than preoperative dyspareunia after all surgery types.; Conclusion: Sexual function comparisons are most robust between transvaginal synthetic mesh and native tissue repairs and show similar prevalence of sexual activity, de novo dyspareunia, and sexual function scores. Total dyspareunia is higher after transvaginal synthetic mesh than sacrocolpopexy. Although sexual function data are sparse in the other comparisons, no other differences in sexual activity, dyspareunia, and sexual function score change were found. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Antoun, L., et al. (2023). "LAparoscopic Versus Abdominal hysterectomy (LAVA): protocol of a randomised controlled trial." BMJ Open 13(9): e070218.
	Introduction There is uncertainty about the advantages and disadvantages of laparoscopic hysterectomy compared with abdominal hysterectomy, particularly the relative rate of complications of the two procedures. While uptake of laparoscopic hysterectomy has been slow, the situation is changing with greater familiarity, better training, better equipment and increased proficiency in the technique. Thus, a large, robust, multicentre randomised controlled trial (RCT) is needed to compare contemporary laparoscopic hysterectomy with abdominal hysterectomy to determine the safest and most cost-effective technique. Methods and analysis A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation. A within trial-based economic evaluation will explore the cost-effectiveness of laparoscopic hysterectomy compared with open abdominal hysterectomy. We will aim to recruit 3250 women requiring a hysterectomy for a benign gynaecological condition and who were suitable for either laparoscopic or open techniques. The primary outcome is major complications up to six completed weeks postsurgery and the key secondary outcome is time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation is to be cost per QALY at 12 months' postsurgery. A secondary analysis is to be undertaken to generate costs per major surgical complication avoided and costs per return to normal activities. Ethics and dissemination The study was approved by the West Midlands-Edgbaston Research Ethics Committee, 18 February 2021 (Ethics ref: 21/WM/0019). REC approval for the protocol version 2.0 dated 2 February 2021 was issued on 18 February 2021. We will present the findings in national and international conferences. We will also aim to publish the findings in high impact peer-reviewed journals. We will disseminate the completed paper to the Department of Health, the Scientific Advisory Committees of the RCOG, the Royal College of Nurses (RCN) and the BSGE. Trial registration number ISRCTN14566195.Copyright © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Anufrieva, K. S., et al. (2023). "Unlocking DNA Damage Sensitivity of Cancer Cells: The Potential of Splicing Inhibitors." bioRxiv.
	Despite the growing interest in pre-mRNA alternative splicing (AS) as a therapeutic anticancer target, the potential of splicing inhibitors in treating solid tumors remains largely unexplored. We conducted a meta-analysis of transcriptome data from six different tumor types and revealed that splicing inhibitors induced similar patterns of AS, resulting in widespread exon-skipping and intron retention events that often lead to nonsense-mediated decay of the transcripts. Interestingly, in many cases exon skipping is induced by a compensatory cellular response to splicing inhibitor treatment. It involves an upregulation of multiple splicing factors and incomplete recognition of branch points by U2 snRNP. These post transcriptional changes downregulate one-third of essential DNA repair genes, thereby creating a therapeutic vulnerability that can be exploited for cancer treatment. To harness this vulnerability, we proposed a new approach to cancer treatment consisting of sequential addition of a splicing inhibitors followed by a DNA-damaging agent. Our in vitro and in vivo experiments demonstrated that this strategy exhibits promising therapeutic potential for a wide range of tumors.Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Aoyama, T., et al. (2021). "Effects of Goshajinkigan (TJ-107) for oxaliplatin-induced peripheral neurotoxicity using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire in a Phase II, multicenter, randomized, double-blind, placebo-controlled trial." Journal of cancer research and therapeutics 17(6): 1473-1478.
	BACKGROUND: The aim of the present study was to evaluate the efficacy of TJ-107 for oxaliplatin-induced peripheral neurotoxicity in prospective, multi-institutional, randomized, double-blind, placebo-controlled Phase II trials using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire (FACT-GOG-NTX-12). PATIENTS AND METHODS: The patients who were registered to the Goshajinkigan oxaliplatin neurotoxicity evaluation study (UMIN000002211) were analyzed. A NTX-12 from the validated FACT/GOG-NTX-12 was assessed before treatment and at the end of every 2 cycles. RESULTS: The comparisons of the median scores for TJ-107 and the placebo at 8 and 26 weeks were as follows: numbness or tingling in the hands (P = 0.5820), numbness or tingling in the feet (P = 0.3236), feeling of discomfort in the hands (P = 0.8219), feeling of discomfort in the feet (P = 0.5361), joint pain or muscle cramps (P = 0.1974), feeling weak all over (P = 0.2771), trouble hearing (P = 0.2832), ringing or buzzing in ears (P = 0.1031), trouble buttoning buttons (P = 0.1653), trouble feeling the shape of small objects when held in hand (P = 0.2919), trouble walking (P = 0.5406), and pain in the hands or feet when exposed to cold temperatures (P = 0.1872). CONCLUSION: There might be no clinically significant difference between the use of TJ-107 and the severity and quality of life for patients treated with oxaliplatin.

Apolikhina, I. A., et al. (2023). "SYSTEMATIC REVIEW OF THE EFFICACY AND SAFETY OF NIFURATEL FOR WOMEN WITH DISEASES ACCOMPANIED BY PATHOLOGICAL DISCHARGE FROM THE GENITAL TRACT." Akusherstvo i Ginekologiya (Russian Federation) 2023(11): 48-58.
	Objective: To evaluate the clinical and laboratory efficacy and safety of nifuratel for women with diseases accompanied by pathological discharge from the genital tract. Material(s) and Method(s): This systematic review was conducted according to the PRISMA checklist. The analysis included controlled clinical studies for the period 1972-2023 which evaluated the efficacy and safety of oral and/or vaginal administration of nifuratel in women over the age of 18 with bacterial vaginosis, aerobic vaginitis, candidiasis vulvovaginitis, mixed vaginitis and trichomoniasis. Result(s): After selecting the proper publications and excluding duplicates, the qualitative analysis included 14 studies (5 randomized and 9 non-randomized); totally, there were 3,337 patients including 544 pregnant women. The quantitative synthesis and meta-analysis included 9 clinical studies. According to received data, a statistically significant difference in clinical and microbiological efficacy was determined in favor of nifuratel in comparison with other drugs (odds ratio (OR)=1.03, 95% CI [1.00, 1.07], p=0.03 and OR=1.15, 95% CI [1.04, 1.27], p=0.005, respectively). There was a statistically significant difference in the frequency of relapses after a course of therapy in favor of nifuratel in comparison with other drugs (OR=0.36, 95% CI [0.19, 0.68], p=0.001). None of the included studies showed any serious side effects after the treatment with the drug. Conclusion(s): The use of nifuratel both as monotherapy and in combination with nystatin surpasses other drugs in clinical and microbiological efficacy in the treatment of diseases accompanied by pathological discharge from the genital tract in women; it also shows a lower frequency of relapses. Nevertheless, additional well-planned studies with standardized criteria for evaluating results and long-term follow-up periods can allow the women with vaginitis and bacterial vaginosis to make a better choice among antimicrobial therapy options.Copyright © A group of authors, 2023.

Ara, U., et al. (2021). "Effectiveness of inositol, metformin and their combination in women with PCOS undergoing assisted reproduction: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Ara, U., et al. (2021). "Efficacy of photodynamic therapy in women with HSIL and LSIL and early stage of squamous cervical cancer: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Ara, U., et al. (2021). "Effect of menopausal hormone therapy on skin elasticity in women: a systematic review and meta-analysis."
	
Arab, A., et al. (2019). "The Association Between Vitamin D and Premenstrual Syndrome: A Systematic Review and Meta-Analysis of Current Literature." Journal of the American College of Nutrition 38(7): 648-656.
	A number of studies have assessed the association between vitamin D and premenstrual syndrome (PMS) in different populations, but the findings have been inconclusive. Herein, we systematically reviewed available observational and interventional evidence to elucidate the overall relationship between vitamin D and PMS. PubMed, Cochrane Library, ScienceDirect, Scopus, Google Scholar, and ISI Web of Science databases were searched for all available articles until September 2018. The Newcastle-Ottawa quality assessment scale and Jadad scale were used to assess the quality of the observational and interventional studies, respectively. A total of 16 studies out of 196 met our inclusion criteria and were included in the final analysis. Although no significant association between serum 25(OH)D and PMS (weighted mean difference (WMD) = 3.35; 95% confidence interval, -7.80 to 1.11; p = 0.14) was indicated in observational studies, vitamin D supplementation was effective in ameliorating PMS symptoms based upon findings from interventional studies. These results add to the existing literature supporting the fact that nutrition, especially vitamin D, plays an important role in women's health. Additional well-designed clinical trials should be considered in future research to develop firm conclusions on the efficacy of vitamin D on PMS. KEY TEACHING POINTS 5-8% of women experience severe PMS. Nutrition especially vitamin D plays an important role in the women's health. Vitamin D could exert significant clinical effects on PMS symptoms. This is a systematic review and meta-analysis in this regard.

Aranda-Gutierrez, A., et al. (2024). "Obstetric and neonatal outcomes following taxane use during pregnancy: a systematic review." BMC Cancer 24(1): 9.
	Background: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited.; Methods: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken.; Results: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia.; Conclusions: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety. (© 2023. The Author(s).)

Araújo Isabelle Maria Mendes, d., et al. (2021). "Non-pharmacological therapeutic approaches to painful sexual dysfunction in women: integrative review." BrJP 4(3): 239-244.
	ABSTRACT BACKGROUND AND OBJECTIVES: Sexual dysfunctions associated with pain symptoms can affect female genito-pelvic functionality. The objective of this study was to identify non-pharmacological analgesic therapies used in painful sexual dysfunctions to guide clinical and therapeutic practice in comprehensive care of women's sexual health. CONTENTS: An integrative review, carried out in the Pubmed, LILACS, Scielo, PEDro and Biblioteca Virtual de Saúde databases. The searches were performed using the combinations: "dysfunction" AND "pain" AND "sexual" AND "treatment". The inclusion criteria allowed the analysis of six articles published between January 2009 and August 2019. It was observed that dysfunctions in the muscles of the pelvic floor may be associated with pain and sexual dysfunctions, thus, non-pharmacological analgesic interventions can provide greater muscle relaxation and perineal self-perception, reducing painful symptoms in the sexual response cycle. CONCLUSION: The treatment of painful sexual dysfunctions with the use of non-pharmacological resources, using techniques such as perineal massage, myofascial release, muscle training, biofeedback, vaginal dilators, electrostimulation, and radiofrequency aim to improve sexual performance and quality of life for women.

Aravantinou-Fatorou, A., et al. (2021). "Pembrolizumab in endometrial cancer: Where we stand now." Oncology Letters 22(6): 821.
	Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms 'endometrial cancer' and 'pembrolizumab'. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice.; Competing Interests: FZ has received honoraria for lectures and has served in an advisory role for Astra-Zeneca, Daiichi, Eli-Lilly, Merck, Novartis, Pfizer and Roche. ML has received honoraria from Roche, Astra Zeneca, Astellas, MSD, Janssen, BMS and IPSEN. MG has received honoraria from Janssen, Genesis Pharm, Amgen, Karyopharm and Takeda. MAD has received honoraria and has served on advisory boards from Jannsen, Genesis Pharm, Amgen, Karyopharm and Takeda, outside the submitted work. AAF, AA, VEG and OF declare that they have no competing interests. (Copyright: © Aravantinou-Fatorou et al.)

Aravantinou-Fatorou, A., et al. (2021). "Pembrolizumab in endometrial cancer: Where we stand now (Review)." Oncology Letters 22(6): 13082.
	Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combina- tion of the terms 'endometrial cancer' and 'pembrolizumab'. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice.Copyright © 2021 Spandidos Publications. All rights reserved.

Aravive, I., et al. (2021). Batiraxcept (AVB-S6-500)/Placebo in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer.
	No Results Available Drug: Batiraxcept|Drug: Paclitaxel|Other: Placebo Anti-tumor activity of batiraxcept in combination with PAC measured by progression free survival (PFS) in patients receiving batiraxcept + PAC versus patients receiving Placebo+PAC|Overall survival Female Phase 3 366 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment AVB500-OC-004|GOG-3059|ENGOT OV66|AXLerate-OC August 4, 2023

Arch, J. (2023). "A Telehealth Acceptance and Commitment Therapy Intervention for Women with Advanced Ovarian Cancer and PARP Inhibitor-Related Fatigue: Preliminary Findings from a Pilot Randomized Trial." Psycho-Oncology 32(Supplement 1): 40-41.
	Background/Purpose: Oral PARP inhibitors have dramatically changed treatment for many women with advanced ovarian cancer, and are increasingly used to treat other advanced cancers (with over 300 active clinical trials). However, PARP inhibitors cause significant fatigue for nearly half of patients. Though cognitive behavioral approaches represent one of the most effective strategies for treating cancer-related fatigue, a recent Cochrane meta-analyses found very low quality evidence and no enduring benefit to address fatigue in advanced cancer; further, there are no trials in the context of PARP inhibitors. Finally, existing cancer-related fatigue interventions have generally been delivered in person over many sessions, limiting their accessibility and scalability. Method(s): In a pilot randomized trial among fatigued adults with latestage/ recurrent ovarian cancer on PARP inhibitors (n = 36), we developed, refined, and piloted a 6-session telehealth intervention. The intervention, known as REVITALIZE, was based on acceptance and commitment therapy and addressed modifiable contributors to PARP inhibitor-related fatigue. The trial randomized patients 1:1 to REVITALIZE or an enhanced usual care control across two sites, evaluated feasibility, acceptability, and preliminary efficacy through 3-month follow-up, and conducted exit interviews with all REVITALIZE patients. Result(s): The trial met or exceeded its acceptability and feasibility goals; exit interviews further indicated high acceptability. Relative to enhanced usual care, REVITALIZE significantly reduced fatigue interference at 12-week follow-up, p = 0.01, by a large effect (d = 0.84), improved current fatigue levels, fatigue self-efficacy, fatigue catastrophizing, depression, anxiety, and quality of life (ds = 0.43-0.67), and demonstrated a pattern of fewer PARP inhibitor dose reductions and delays. Conclusions and Implications: Among adults with advanced ovarian cancer on PARP inhibitors, a brief telehealth intervention based on acceptance and commitment therapy showed strong feasibility, acceptability, and efficacy potential to improve fatigue outcomes as well as anxiety, depression, and quality of life outcomes. This approach has good scalability potential and is worthy of further investigation.

Archer, D. F., et al. (2022). "Efficacy Outcomes with Relugolix Combination Therapy in Perimenopausal Women with Uterine Fibroids: LIBERTY Studies." Menopause 29(12): 1460.
	Objective: In the 24-week, Phase 3 LIBERTY 1 and 2 studies, relugolix combination therapy (Rel-CT; relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) significantly reduced menstrual blood loss (MBL) in women with uterine fibroids (UF) and heavy menstrual bleeding. Here, the efficacy and safety of Rel-CT through 24 weeks is reported in a subgroup of potentially perimenopausal women (defined as age >= 45 years) compared with the overall study population (age 18-50 years). Design(s): Premenopausal women with ultrasound-confirmed UF and MBL >=80 mL per cycle were randomized 1:1:1 to Rel-CT or placebo for 24 weeks, or Delayed Rel-CT (relugolix 40 mg monotherapy for 12 weeks, followed by Rel-CT for 12 weeks). Primary efficacy endpoint: proportion of treatment responders, defined as MBL volume <80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment, measured by the alkaline hematin method. Key secondary efficacy endpoints: 1) amenorrhea rate; 2) mean percent reduction in MBL volume; 3) reduction in distress from bleeding, passing of blood clots, and tightness/pressure in the pelvic area, as measured by the Bleeding and Pelvic Discomfort (BPD) scale; 4) proportion of women with moderate-to-severe pain at baseline (Numerical Rating Score [NRS] >=4) achieving minimal-to-no fibroid-associated pain; 5) proportion of women with anemia (hemoglobin <=10.5g/dL) at baseline who achieved an increase in hemoglobin levels of >2 g/dL; 6) percent change in largest UF volume; and 7) percent change in uterine volume. Analyses comparing the Rel-CT group vs placebo group were performed on the modified intent-to-treat population using pooled data from LIBERTY 1 and 2. Proportions were compared using Cochran-Mantel-Haenszel tests, and changes or percent changes from baseline to Week 24 were tested with mixed-effects or ANCOVA models, with treatment, visit, baseline MBL and treatment by visit interaction included as fixed effects. All reported P values are two-sided, and 95% confidence intervals (CIs) for treatment differences are provided. Result(s): Potentially perimenopausal women included 282/768 (36.7%) women from LIBERTY 1 and 2 (95 randomized to Rel-CT; 94 to placebo). Mean [standard deviation] baseline characteristics were similar (except for age) between potentially perimenopausal women and the overall pooled population: age (47.4 [1.7] vs 42.5 [5.2] years, respectively), body mass index (31.1 [6.4] vs 31.2 [7.1] kg/m2), MBL volume (228.6 [146.4] vs 243.0 [182.2] mL). Efficacy results are reported in Table 1. Adverse events for potentially perimenopausal women were consistent with those for the overall population. Conclusion(s): In potentially perimenopausal women from the LIBERTY studies, Rel-CT demonstrated a significant reduction of MBL volume; achievement of amenorrhea; improvements in hemoglobin levels, UF-associated pain and quality of life; and reductions in UF volume vs placebo, and was generally well-tolerated through 24 weeks. Results were consistent with the overall study population.

Archer, D. F., et al. (2019). "Ospemifene for the treatment of menopausal vaginal dryness, a symptom of the genitourinary syndrome of menopause." Expert Review of Endocrinology and Metabolism 14(5): 301-314.
	Introduction: Vulvovaginal atrophy (VVA), a component of the genitourinary syndrome of menopause, is a progressive condition due to decline in estrogen leading to vaginal and vulvar epithelial changes. Accompanying symptoms of dryness, irritation, burning, dysuria, and/or dyspareunia have a negative impact on quality of life. Ospemifene is a selective estrogen receptor modulator (SERM) approved by the FDA for moderate to severe dyspareunia and vaginal dryness due to postmenopausal VVA. Areas covered: PubMed was searched from inception to March 2019 with keywords ospemifene and vulvar vaginal atrophy to review preclinical and clinical data describing the safety and efficacy of ospemifene for vaginal dryness and dyspareunia due to VVA. Covered topics include efficacy of ospemifene on vaginal cell populations, vaginal pH, and most bothersome VVA symptoms; imaging studies of vulvar and vaginal tissues; effects on sexual function; and safety of ospemifene on endometrium, cardiovascular system, and breast. Expert opinion: Ospemifene is significantly more effective than placebo in all efficacy analyses studied, working through estrogen receptors and possibly androgen receptors. Safety as assessed by adverse events was generally comparable to that with placebo and to other SERMs, and/or adverse events were not clinically meaningful. No cases of endometrial or breast cancer were reported.Copyright © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Arcieri, M., et al. (2024). "Primary flap closure of perineal defects to avoid empty pelvis syndrome after pelvic exenteration in gynecologic malignancies: An old question to explore a new answer." European Journal of Surgical Oncology 50(2): 107278.
	Pelvic exenteration (PE) is a radical oncological surgical procedure proposed in patients with recurrent or persistent gynecological cancers. The radical alteration of pelvic anatomy and of pelvic floor integrity can cause major postoperative complications. Fortunately, PE can be combined with reconstructive procedures to decrease complications and functional and support problems of pelvic floor, reducing morbility and mortality and increasing quality of life. Many options for reconstructive surgery have been described, especially a wide spectrum of surgical flaps. Different selection criteria have been proposed to select patients for primary perineal defect flap closure without achieving any strict indication of the best option. The aim of this review is to focus on technical aspects and the advantages and disadvantages of each technique, providing an overview of those most frequently used for the treatment of pelvic floor defects after PE. Flaps based on the deep inferior epigastric artery, especially vertical rectus abdominis musculocutaneous (VRAM) flaps, and gracilis flaps, based on the gracilis muscle, are the most common reconstructive techniques used for pelvic floor and vaginal reconstruction. In our opinion, reconstructive surgery may be considered in case of total PE or type II/III PE and in patients submitted to prior pelvic irradiation. VRAM could be used to close extended defects at the time of PE, while gracilis flaps can be used in case of VRAM complications. Fortunately, numerous choices for reconstructive surgery have been devised. As these techniques continue to evolve, it is advisable to adopt an integrated, multi-disciplinary approach within a tertiary medical center.Copyright © 2023 The Author(s)

Arend, R., et al. (2023). "DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma." Gynecologic Oncology 172: 82-91.
	Purpose: Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival. DKN-01 is a humanized monoclonal antibody with DKK1 neutralizing activity that may provide clinical benefit to patients whose tumors have overexpression of DKK1 or Wnt genetic alterations.; Methods: We conducted an open-label, Phase 2 basket study with 2-stage design in patients with endometrial carcinoma (EC) and platinum-resistant/refractory epithelial ovarian cancer. DKN-01 was administered either as monotherapy or in combination with weekly paclitaxel at investigator's discretion. All patients underwent NGS testing prior to enrollment; tumor tissue was also tested for DKK1 expression by RNAscope pre-treatment and after cycle 1 if available. At least 50% of patients were required to have a Wnt signaling alteration either directly or tangentially. This publication reports results from the EC population overall and by DKK1-expression.; Results: DKN-01 monotherapy and in combination with paclitaxel was more effective in patients with high DKK1-expressing tumors compared to low-expressing tumors. DKN-01 monotherapy demonstrated an objective response rate [ORR] of 25.0% vs. 0%; disease control rate [DCR] of 62.5% vs. 6.7%; median progression-free survival [PFS] was 4.3 vs. 1.8 months, and overall survival [OS] was 11.0 vs. 8.2 months in DKK1-high vs DKK1-low patients. Similarly, DKN-01 in combination with paclitaxel demonstrated greater clinical activity in patients with DKK1-high tumors compared to DKK1-low tumors: DCR was 55% vs. 44%; median PFS was 5.4 vs. 1.8 months; and OS was 19.1 vs. 10.1 months. Wnt activating mutations correlated with higher DKK1 expression. DKN-01 was well tolerated as a monotherapy and in combination with paclitaxel.; Conclusions: Collectively, data demonstrates promising clinical activity of a well-tolerated drug, DKN-01, in EC patients with high tumoral DKK1 expression which frequently corresponded to the presence of a Wnt activating mutation. Future development will focus on using DKN-01 in DKK1-high EC patients in combination with immunotherapy.; Competing Interests: Declaration of Competing Interest Dr. Arend participates in Data Safety Monitoring/Advisory Boards (DSMB) for Astra Zeneca, Caris Life Sciences, Clovis, Merck, Seagen, Sutro, Glaxo Smith Kline, VBL Therapeutics. Dr. Matulonis reports relationships with the Med Learning Group and participates in DSMB for: Allarity, NextCure, Alkermes, Symphogen, Trillium, Agenus, Immunogen, Novartis, Boerhinger Ingelheim, Rivkin Foundation, Ovarian Cancer Research Alliance, Clearity Foundation, and Morphosys. Dr. Kagey and Dr. Sirard are employed by and own stock in Leap Therapeutics. Dr. Hamilton reports consulting or advisory for: Pfizer (Inst), Genentech/Roche (Inst), Lilly (Inst), Puma Biotechnology (Inst), Daiichi Sankyo (Inst), Mersana (Inst), Boehringer Ingelheim (Inst), AstraZeneca (Inst), Novartis (Inst), Silverback Therapeutics (Inst), Black Diamond (Inst). Dr. Sachdev participates in DSMB for Pfizer, Immunomedics, AstraZeneca, Tempus, and Ipsen; discloses stock/options in Biosplice Therapeutics; and is employed by Biosplice Therapeutics. Dr. Duska reports royalties from JB Learning, consulting fees from UpToDate, serves as an expert law review, and participates in DSMB for Regeneron and Inovio. She reports leadership in SGO, ASCO, the NCI, and the British Journal of OBGYN. Dr. ElNaggar reports employment and stock/options with Natera. Ms. Liu and Ms. Piper were employed by LEAP Therapeutics during manuscript preparation. Dr. O'Malley participates in DSMB for: AbbVie, AdaptImmune, Agenus, Arquer Diagnostics, Arcus Biosciences, AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Biom, Eisai, Elevar, Exelixis, Genentech, Genelux, GlaxoSmithKline, GOG Foundation, Hoffman-LaRoche, ImmunoGen, Imvax, InterVenn, INX ED, IOVANCE Biotherapeutics, Janssen, Laekna, Leap Therapeutics, Luzsana Biotechnology, Merck, Merck Sharp & Dohme, Mersana, Myriad, Novartis, NovoCure, OncoC4, Onconova, Regeneron, RepImmune, R Pharm, Roche, SeaGen, Sorrento, Sutro, Tarveda, Toray, Trillium, Umoja, Verastem, VBL Therapeutics, Vincerx, Xencor, Zentalis. All other authors report no disclosures. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Arend, R. C., et al. (2021). "Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer." Gynecologic Oncology 161(2): 496-501.
	OBJECTIVE: Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-cancer gene therapy, in combination with paclitaxel in patients with platinum resistant ovarian cancer (PROC). METHODS: The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. RESULTS: The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. CONCLUSIONS: At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified.

Aretha, G., et al. (2024). "The Effects of Probiotics in the Treatment of Vaginal Candidiasis: A Systematic Review."
	
Ari Sabahattin, A., et al. (2022). "Effectiveness of paracervical block in endometrial sampling procedures for pain control: a randomized controlled clinical trial." Ginekologia polska 93(11): 889-895.
	Objectives: We aimed to evaluate the effect of paracervical block (PCB) on endometrial sampling procedures, to assess the effect on pain of waiting between PCB and intervention, and to compare the effectiveness of PCB with oral non-steroidal anti-inflammatory drugs (NSAID) for decreasing the pain levels associated with endometrial biopsy.; Material and Methods: A total of 123 participants were divided into four groups as Group 1: Waiting 1 minute after PCB, Group 2: Waiting 3 minute after PCB, Group 3: Control group, and Group 4: Waiting 60 minute after taking oral NSAIDs. The success of analgesic measures used for endometrial biopsy during and 30 minutes after the procedure was compared with the Numeric Pain Rating Scale (NPRS) system.; Results: The Numeric Pain Rating Scale (NPRS) 0 score was 2.60 (± 2.42) in Group 1; 1.60 (± 1.73) in Group 2; 5.30 (± 2.10) in Groups 3; 5.63 (± 1.99) in Groups 4. NPRS 30 score was 0.80 (± 0.88) in Group 1; 0.43 (± 0.81) in Group 2; 1.90 (± 1.32) in Groups 3; 2.70 (± 1.41) in Groups 4. The pain was significantly less in the paracervical block groups compared to control and oral NSAIDs groups. However, there was no significant difference in NPRS 0 (p = 0.196) and NPRS 30 (p = 0.191) scores between Group 1 and Group 2. There was no significant difference in NPRS 0 and NPRS 30 scores between control group and oral NSAID group.; Conclusions: Paracervical block (PCB) is an effective method and superior to oral NSAIDs. Waiting 1 minute or 3 minutes after PCB were equally effective.

Arian Sara, E., et al. (2023). "Endometrial receptivity array before frozen embryo transfer cycles: a systematic review and meta-analysis." Fertility and Sterility 119(2): 229-238.
	Objective: To investigate the impact of endometrial receptivity array (ERA) before frozen embryo transfer in patients undergoing in vitro fertilization (IVF). There is a lack of consensus regarding the use of ERA for increasing the success rate of IVF cycles, mainly in terms of the live birth rate.; Design: PubMed, Web of Science and Embase were searched from inception up to February 15, 2022.; Setting: Not applicable.; Patient(s): Patients undergoing ERA vs no ERA before frozen embryo transfer.; Intervention(s): Only comparative studies evaluating pregnancy rates of patients undergoing frozen embryo transfer cycles with or without prior ERA were included. Inter-study heterogeneity was also assessed using Cochrane's Q test and the I 2 statistic. The random-effects model was used to pool the odds ratio (OR) with the corresponding 95% confidence intervals (CIs). Subgroup analyses were performed to investigate the impact of ERA on pregnancy rates according to the number of previous embryo transfer (ET) failures (≤ 2 previous failed ETs vs. > 2 failed ETs, defined as recurrent implantation failure). Separate analyses were performed according to the study design and adjustment for confounders.; Main Outcome Measures(s): The primary outcomes of the study were live birth rate and/or ongoing pregnancy rate. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate, and miscarriage rate were considered secondary outcomes.; Result(s): Eight studies (representing data on n = 2,784 patients; n = 831 had undergone ERA and n = 1,953 without ERA) were found to be eligible for this meta-analysis. The live birth or ongoing pregnancy rate for the ERA group was not significantly different compared with the non-ERA group (OR, 1.38; 95% CI, 0.79-2.41; I 2 83.0%), nor was a difference seen in subgroup analyses based on the number of previous failed ETs. The rates of implantation, biochemical pregnancy, clinical pregnancy, and miscarriage were also comparable between the ERA and the non-ERA groups. After separate analyses according to the study design and adjustment for confounding factors, overall pooled estimates remained statistically nonsignificant.; Conclusion(s): The findings of the current meta-analysis did not reveal a significant change in the rate of pregnancy after IVF cycles using ERA, and it is not clear whether ERA can increase the pregnancy rate or not.; Systematic Review Registration: Prospectively registered in PROSPERO (CRD42022310862). (Copyright © 2022. Published by Elsevier Inc.)

Arik Meltem, I., et al. (2022). "The effect of TENS for pain relief in women with primary dysmenorrhea: A systematic review and meta-analysis." Explore (New York, N.Y.) 18(1): 108-113.
	Objective: Primary dysmenorrhea (PD) is a chronic health condition that affects primarily young women and interferes with daily activities, causes loss of work productivity, and reduces quality of life. Transcutaneous electrical nerve stimulation (TENS) is a complementary and alternative therapy used to reduce pain related to PD. The purpose of this meta-analysis study was to evaluate the effectiveness of TENS in the treatment of pain in women with PD.; Methods: A search of the English literature in the Cochrane Library, MEDLINE (EBSCO), Physiotherapy Evidence Database (PEDro), CINAHL (EBSCO), PUBMED, OVID, Science Direct, Scopus, Academic Search Complete databases was conducted using combinations of the following search terms: 'primary dysmenorrhea', 'pain', 'transcutaneous electrical nerve stimulation', 'TENS', and 'electrical stimulation'. All content from database inception through April 2020 was included in the search.; Results: The initial search strategy based on date range and language yielded 571 relevant records and 4 of them were about both TENS and PD. A total of 260 patients were enrolled in the included studies. In all of the included studies, the comparison intervention consisted of sham TENS. The primary outcome of interest was pain intensity. Our analysis indicated that TENS was statistically more effective than sham TENS in reducing PD-related pain (SMD=1.384; 95% CI=0.505, 2.262; p = 0.002).; Conclusion: TENS is a safe and well-tolerated electrophysical therapy that may be effective for relieving pain in PD. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Armah, D., et al. (2021). "Holistic management of female infertility: A systematic review." African journal of reproductive health 25(2): 150-161.
	Although issues pertaining to infertility affect both males and females, women often become victims of stigmatization and rejection, making them susceptible to emotional pain and suffering. Due to these psychosocial problems, they require not only biomedical treatment, but also psychological, social, and spiritual support. Unfortunately, many women with infertility are not treated holistically. The aim of this review was to retrieve existing evidence of holistic healthcare interventions for women with infertility. Global databases were searched for articles published anywhere in the world between 2010 to 2018 that explored holistic healthcare interventions for women diagnosed with infertility. A total of 18 articles meeting the inclusion criteria were assessed, and data extraction was performed. Findings revealed that interventions adopted in managing infertile women alongside the bio-medical management included: counseling; cognitive behavioral therapy; acceptance and commitment therapy; educational interventions; spiritual interventions; emotionally focused therapy/intervention and integrative body-mind-spirit interventions. The results of this review have implications for healthcare professionals to ensure holistic care of women diagnosed with infertility in Ghana and Africa at large.

Armbrust, R., et al. (2021). "Impact of health-related quality of life (HRQoL) on short-term mortality in patients with recurrent ovarian, fallopian or peritoneal carcinoma (the NOGGO-AGO QoL Prognosis-Score-Study): results of a meta-analysis in 2209 patients." ESMO Open 6(2): 100081.
	Objective: Recurrent ovarian cancer is an incurable disease with variable but poor prognosis. Health-related quality of life (HRQoL) is a patient-reported outcome measure generally applied to measure effects of therapies. Our aim was the development and validation of a risk score for the prediction of short-term mortality using the combination of sociodemographic and clinical factors and HRQoL.; Methods: For exploratory and validation analysis, the North-Eastern German Society of Gynecological Oncology (NOGGO) and Working Group Gynecological Oncology (AGO) study databases were screened for trials. Only trials which obtained defined HRQoL measurements were included in the final analysis. Multivariable logistic regression analyses were used to identify risk factors and their weighting for the risk score. Modulation with cubic regression analyses revealed median survival and short-term mortality defined as 1-year mortality for each value.; Results: For exploration, 974 patients from three clinical studies of the NOGGO and for validation, 1235 patients from several clinical studies of the AGO were eligible. The risk score included platinum-free interval, performance status, age, global QoL and nausea/vomiting. Receiver operating characteristic analysis showed a good predictive value with an area under the curve of 0.81 for model 1 in the exploration and 0.74 in the validation. Short-term mortality in model 1 was 8.2%, 23.5% and 58.4% in the exploration sample, and 19.7%, 38.1% and 63.4% in the validation sample for patients under low, medium and high risk, respectively.; Conclusions: This risk score discriminates well between recurrent ovarian cancer patients under low, medium and high risk of short-term mortality. It may help to identify a risk group under high risk for short-term mortality that can be used for randomization in clinical trials and may support decision making for palliative chemotherapy.; Competing Interests: Disclosures The authors have declared are no conflicts of interest. (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Armbruster, S. D., et al. (2021). "A phase III study of transdermal granisetron versus oral ondansetron for women with gynecologic cancers receiving pelvic chemoradiation." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 29(1): 213-222.
	PURPOSE: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4-7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. METHODS: In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. RESULTS: Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2-64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4-56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. CONCLUSION: Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.

Armeni, E. and I. Lambrinoudaki (2022). "Menstrual irregularity and bone health in premenopausal women: Are oral contraceptives the best option?" Maturitas 155: 70-71.
	Competing Interests: The authors declare that they have no competing interests.

Armour, M., et al. (2021). "The effectiveness of a modified Gui Zhi Fu Ling Wan formulation (Gynoclear™) for the treatment of endometriosis: a study protocol for a placebo-controlled, double-blind, randomised controlled trial." Trials 22(1): 299.
	Background: Endometriosis is the presence of tissue similar to that of the endometrium outside the uterine cavity and is the most common cause of chronic pelvic pain. Current non-surgical treatments such as non-steroidal anti-inflammatories, oral contraceptive pills and hormonal treatments have limited effectiveness, and the side effect profile is bothersome. This study will evaluate the efficacy of Gynoclear™ by change in endometriosis-related pain based on the Endometriosis Pain Daily Diary (EPPD) scores.; Methods: This randomised, double-blind, placebo-controlled trial will recruit a minimum of 90 adult participants across Australia who have a laparoscopic visualisation/confirmation of endometriosis in the last 5 years and have current moderate or greater pelvic pain. Participants will be randomly allocated in a 1:1 ratio to receive either Gynoclear™ (active) or placebo. Gyncolear's active ingredients are Carthamus tinctorius (Safflower), Cinnamomum cassia (Chinese cinnamon), Poria cocos (Hoelen), Paeonia suffriticosa (Tree peony), Paeonia lactiflora (Peony) and Salvia miltiorrhiza (Red sage). Participants are asked to complete a total of 5 months' worth of pain diary entries via the EPDD v3, including 1-month screening, 2-month treatment period and 1-month post-treatment follow-up. The primary outcome variable is change in endometriosis-related pain based on the EPDD v3 scores. Secondary outcomes include change in health-related quality of life via the Endometriosis Health Profile (EHP-30), SF-12 and EQ-5D scores as well as changes in rescue analgesic usage, dyspareunia and fatigue via the EPDD.; Discussion: This study will determine the safety and efficacy of Gynoclear™ to reduce the severity and duration of non-cyclical pelvic pain, dysmenorrhoea, dyspareunia and other symptoms of endometriosis. Study outcomes will be of interest to health professionals and members of the public who suffer from endometriosis.; Trial Registration: Australia and New Zealand Clinical Trials Registry ACTRN12619000807156 . Registered on 3 June 2019.

Armstrong, E., et al. (2022). "Metronidazole treatment rapidly reduces genital inflammation through effects on bacterial vaginosis-associated bacteria rather than lactobacilli." The Journal of clinical investigation 132(6).
	BackgroundBacterial vaginosis (BV) causes genital inflammation and increases HIV risk, whereas a vaginal microbiota dominated by Lactobacillus species is associated with immune quiescence and relative HIV protection. BV treatment reduces genital inflammation, but it is unclear whether this reduction is driven by a decrease in BV-associated bacteria or an increase in Lactobacillus species.METHODSTo evaluate the short-term effect of standard BV treatment on genital immunology and the vaginal microbiota, vaginal swabs were collected immediately before and after metronidazole treatment for BV and analyzed with multiplex ELISA, metagenomic sequencing, and quantitative PCR.RESULTSTopical metronidazole treatment rapidly reduced vaginal levels of proinflammatory cytokines, chemokines, and soluble immune markers of epithelial barrier disruption. Although the vaginal microbiota shifted to dominance by L. iners or L. jensenii, this proportional shift was primarily driven by a 2 to 4 log10-fold reduction in BV-associated bacteria absolute abundance. BV treatment induced no change in the absolute abundance of L. crispatus or L. iners and only minor (<1 log10-fold) increases in L. gasseri and L. jensenii that were not independently associated with reduced inflammation in multivariable models.CONCLUSIONThe genital immune benefits that are associated with Lactobacillus dominance after BV treatment were not directly attributable to an absolute increase in lactobacilli, but rather to the loss of BV-associated bacteria.Trial REGISTRATIONParticipants were recruited as part of a randomized controlled trial (ClinicalTrials.gov NCT02766023) from 2016 to 2019.FUNDINGCanadian Institutes of Health Research (PJT-156123) and the National Institute of Allergy and Infectious Diseases (HHSN2722013000141 and HHSN27200007).

Armstrong, E., et al. (2022). "Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial." The Lancet. Microbe 3(6): e435-e442.
	Background: Bacterial vaginosis might increase HIV risk by eliciting genital inflammation and epithelial barrier disruption, whereas vaginal Lactobacillus crispatus is associated with immune quiescence and HIV protection. We investigated the effect of a live biotherapeutic containing L crispatus CTV-05 (LACTIN-V) on genital immunology and key vaginal bacteria.; Methods: This substudy included women aged 18-45 years who participated in the randomised, placebo-controlled, phase 2b trial of LACTIN-V to reduce bacterial vaginosis recurrence, conducted at four universities and hospitals in the USA. Women with negative results for sexually transmitted infection, pregnancy, and urinary tract infection were provided a 5-day course of vaginal metronidazole 0·75% gel. Those who met at least three of four clinical Amsel criteria for bacterial vaginosis and had a Nugent score of 4-10 from Gram staining were eligible. Participants in the LACTIN-V trial were randomly assigned (2:1) to receive either LACTIN-V or placebo, applied vaginally once per day for 5 days during the first week and then twice per week for 10 more weeks. Follow-up visits occurred 4, 8, 12, and 24 weeks after enrolment. Soluble immune factors and the absolute abundance of bacterial taxa were assayed by mutliplex ELISA and quantitative PCR. The primary outcomes were vaginal levels of IL-1α and soluble E-cadherin at 24 weeks (ie, 13 weeks after treatment cessation).; Findings: Between Feb 21, 2020 and March 18, 2021, we characterised genital immune parameters and the vaginal microbiota in a subset of 66 highly adherent participants who were randomly selected, with no exclusion criteria, from those who had attended all study follow-up visits (n=166) in the larger LACTIN-V clinical trial (n=288). 32 (48%) participants received LACTIN-V and 34 (52%) received placebo. LACTIN-V treatment was significantly associated with lower concentrations of the proinflammatory cytokine IL-1α (β coefficient 0·310, SE 0·149; p=0·042) and soluble E-cadherin (0·429, 0·199; p=0·035), a biomarker of epithelial barrier disruption.; Interpretation: Vaginal administration of LACTIN-V following standard bacterial vaginosis therapy resulted in a sustained reduction in genital inflammation and a biomarker of epithelial integrity. The potential of LACTIN-V to reduce HIV susceptibility merits further investigation.; Funding: Canadian Institutes of Health Research and the National Institutes of Health National Institute of Allergy and Infectious Diseases.; Competing Interests: Declaration of interests CRC is chair of the scientific advisory board for Osel. BC reports grants from Western Foundation, Canadian Institutes of Health Research, Canadian Cancer Society, McLaughlin Foundation, National Cancer Institute, and Cystic Fibrosis Foundation; and material receipts for research from Nubiyota. CRC reports grants from the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases and NIH National Institute of Child Health and Human Development (HHSN2722013000141 and HHSN27200007); and holds stock options in Osel and Evvy. RK reports a grant from Canadian Institutes of Health Research (#PJT-156123). All other authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Arnreiter, C. and P. Oppelt (2021). "A Systematic Review of the Treatment of Uterine Fibroids Using Transcervical Ultrasound-Guided Radiofrequency Ablation with the Sonata® System." Journal of Minimally Invasive Gynecology.
	OBJECTIVE: To evaluate the treatment success, possible side effects, and safety of radiofrequency ablation with the Sonata® System. DATA SOURCES: An electronic literature search in the PubMed and MEDLINE database was carried out from inception to August 2020. METHODS OF STUDY SELECTION: The review was performed in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Keywords such as "Sonata," "transcervical ablation," and "uterine myoma" were used to identify all relevant articles independently by both authors. Full-text articles in English that reported at least one of the following outcomes were included in the study: reduction in perfused/absolute myoma volume, effect of treatment on bleeding intensity and myoma-related symptoms, number of surgical reinterventions, adverse events, return to activities of daily life, effects on surrounding tissue and safety during pregnancy. TABULATION, INTEGRATION AND RESULTS: 10 studies matching the inclusion criteria were identified and used for further analysis. A reduction in total and perfused myoma volume of 63.2% and 64.5% was achieved. One of the studies showed a 53.8 ± 50.5% (n=48) reduction in Menstrual Pictogram Score and another study a 51.1 ± 40.9% (n=142) reduction in Pictoral Blood Loss Assessment Chart at 12 months, and 87.2% (n=190) reported a clinically meaningful reduction in menstrual blood loss after 12 months. While Symptom Severity Scores dropped by 28.8 ± 19.3, 23.3 ± 23.7, and 23.7 ± 19.4 points at 3, 6, and 12 months, respectively, Health-Related Quality of Life Scores increased to 77.5 ± 22.0, 82.8 ± 19.0, and 83.3 ± 20.5 points. One study had an 8% reintervention rate after 12 months and another study showed a 0.7% and 5.2% rate after 12 and 24 months. After an average of 64 months postablation the reintervention rate was 11.8%. Return to activities of daily life was 2.9 ± 2.5 days. No related complications during pregnancy and delivery were reported. CONCLUSION: Radiofrequency ablation with the Sonata® System represents a minimally invasive, organ-preserving treatment option in patients with symptomatic uterine myomas, associated with clinically meaningful improvement of myoma related symptoms.

Arnreiter, C. and P. Oppelt (2021). "A Systematic Review of the Treatment of Uterine Myomas Using Transcervical Ultrasound-Guided Radiofrequency Ablation with the Sonata System." Journal of Minimally Invasive Gynecology 28(8): 1462-1469.
	Objective: To evaluate the treatment success, possible side effects, and safety of radiofrequency ablation with the Sonata System.; Data Sources: An electronic literature search in the PubMed and Medline databases was carried out from inception to August 2020.; Methods of Study Selection: The review was performed in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Keywords such as "Sonata," "transcervical ablation," and "uterine myoma" were used to identify all relevant articles independently by both authors. Full-text articles in English that reported at least 1 of the following outcomes were included in the study: reduction in perfused/total myoma volume, effect of treatment on bleeding intensity and myoma-related symptoms, number of surgical reinterventions, adverse events, return to activities of daily life, effects on surrounding tissue, and safety during pregnancy.; Tabulation, Integration, and Results: 10 studies matching the inclusion criteria were identified and used for further analysis. A reduction in total and perfused myoma volume of 63.2% and 64.5% was achieved. One of the studies showed a 53.8 ± 50.5% (n = 48) reduction in Menstrual Pictogram Score, and another study showed a 51.1 ± 40.9% (n = 142) reduction in Pictorial Blood Loss Assessment Chart at 12 months. 87.2% (n = 190) of the patients reported a clinically meaningful reduction in menstrual blood loss after 12 months. While Symptom Severity Scores dropped by 28.8 ± 19.3, 23.3 ± 23.7, and 23.7 ± 19.4 points at 3, 6, and 12 months, respectively, Health-Related Quality of Life Scores increased to 77.5 ± 22.0, 82.8 ± 19.0, and 83.3 ± 20.5 points. One study had an 8% reintervention rate after 12 months, and another study showed a 0.7% and 5.2% rate after 12 and 24 months. After an average of 64 months after ablation, the reintervention rate was 11.8%. Time to return to activities of daily life was 2.9 ± 2.5 days. No related complications during pregnancy and delivery were reported.; Conclusion: Radiofrequency ablation with the Sonata System represents a minimally invasive, organ-preserving treatment option in patients with symptomatic uterine myomas, associated with clinically meaningful improvement of myoma-related symptoms. (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Aronson, S. L., et al. (2024). "Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer (OVHIPEC-1): Final Survival Analysis of a Randomised, Controlled, Phase 3 Trial." Obstetrical and Gynecological Survey 79(2): 96-98.
	Background: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up.; Methods: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m 2 cisplatin; surgery-plus-HIPEC group). randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed.; Findings: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011).; Interpretation: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery.; Funding: dutch Cancer Foundation (KWF Kankerbestrijding).; Competing Interests: Declaration of interests IHJTdH has received institutional research support from Roche and Quality in Products & Service/RanD. PV has received conference fees and travel expenses from Roche and honoraria from Roche (Genentech), Novartis, and MSD Oncology. KKVdV has served on advisory boards for Exact Sciences and AstraZeneca. GSS has received institutional research support from Merck Sharp & Dohme, Agendia, AstraZeneca, Roche, and Novartis, and consulting fees from Biovica and Seagen. All other authors declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Arsenio, S., et al. (2023). "Recurrent vulvovaginal candidiasis. A network meta-analysis of available pharmacological topical and oral antifungal treatments."
	
Arslanca, T., et al. (2020). "Single-Port Laparoscopic Surgery for Endometrial Cancer: a Systematic Review." Current Obstetrics and Gynecology Reports 9(2): 45-50.
	Purpose of Review: This review aimed to provide an overview of single-port laparoscopic surgery and related literature. Based on previous reviews on endometrial cancer, we focused on the benefit of single-port laparoscopic surgery in endometrium cancer. Recent Findings: Endometrial cancer is the most common gynecological cancer and can be treated with laparoscopic surgery without negatively affecting the oncological outcome. Single-port laparoscopic surgery is a recently emerging endoscopic technique, and it was shown that endometrial cancer could be staged using this method. Summary: Research shows that endometrial staging with SILS is a feasible strategy that might become a common alternative to the conventional laparoscopic technique. In the future, this novel technique might take on a prominent role in advancing the evolution of minimally invasive gynecologic oncology surgery.Copyright © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Artacho-Cordón, F., et al. (2023). "Effect of a Multimodal Supervised Therapeutic Exercise Program on Quality of Life, Pain, and Lumbopelvic Impairments in Women With Endometriosis Unresponsive to Conventional Therapy: A Randomized Controlled Trial." Archives of physical medicine and rehabilitation 104(11): 1785-1795.
	Objective: To evaluate the effectiveness of "Physio-EndEA", a multimodal nine-week supervised exercise intervention, on quality of life, pain, and lumbopelvic impairments in women with endometriosis unresponsive to conventional therapy.; Design: Parallel-group randomized controlled trial. Outcomes were measured at baseline, post-intervention, and at 1 year.; Setting: Two Public University Hospitals.; Participants: This trial included 31 women with endometriosis (N=31) randomly allocated to "Physio-EndEA" group (n=16) or control group (n=15). Four participants dropped out of the study for causes unrelated to the intervention.; Interventions: The "Physio-EndEA" program consisted of a 1-week lumbopelvic stabilization learning phase followed by an 8-week phase of stretching, aerobic, and resistance exercises focused on the lumbopelvic area. It was sequentially instructed and supervised by a trained physiotherapist (with volume and intensity progression) and adapted daily to the potential of each participant. Control group received the usual treatment stipulated by their gynecologist.; Main Outcome Measures: The primary outcome was quality of life. Secondary outcomes were pain intensity, pressure pain thresholds, pain-related catastrophic thoughts, abdominal and back strength, lumbopelvic stability, and muscle architecture.; Results: Adherence rate was 90.6% and mean (±standard deviation) satisfaction was 9.44±0.73 out of 10. No remarkable health problems were reported during the trial. In comparison with controls, the quality of life was improved post-intervention and at 1 year in the Physio-EndEA group with large effect sizes (d>0.80). This group also evidenced: a reduced intensity of dyspareunia, catastrophic thoughts; an increase in pelvic, lumbar, and distal pressure pain thresholds; increases in abdominal and back strength and lumbopelvic stability; and increased thickness of transversus abdominis (right side) and width of lumbar multifidus (left side).; Conclusion: A 9-week program of multimodal supervised therapeutic exercise is a feasible and effective intervention to improve QoL in women with endometriosis. This program also offers benefits in terms of pain/sensitization and lumbopelvic impairments. (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Arumugaswamy, P. R., et al. (2022). "Impact of bariatric surgery on urinary incontinence in morbidly obese individuals." Surgical Endoscopy 36(7): 4771-4779.
	Background: There is scanty evidence on the impact of bariatric surgery on urinary incontinence (UI) in the Asian population. Methodology: Patients who underwent bariatric surgery from June 2018 to June 2019 were screened using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) questionnaire. Patients having UI were identified and followed until 1 year of surgery using the ICIQ-UI-SF. These were classified as having stress, urge, or mixed type of UI. The prevalence, change in scores, and the number of pads used were compared at baseline and at follow-up. Result(s): A total of 148 patients underwent bariatric surgery of whom, 41 patients (M = 2, F = 39) had UI. Stress incontinence was seen in 70.7%, 19.5% had urge incontinence, and rest had the mixed type. Using logistic regression, it was found that female gender was the most important predictor of having UI (OR: 8.33). The prevalence of UI decreased from 27.7% at baseline to 8.1% at 6 months and 3.4% at 12 months. The mean ICIQ-UI-SF score improved from 8.76 (SD = 3.2) at baseline to 0.66 (SD = 2.1) at 12 months of follow-up. The proportion of patients with UI using any number of pads decreased from 92.7% at baseline to 9.8% at 12 months. There was a decrease in the number of patients having moderate to very severe UI from 35 (85.4%) at baseline to 2 (4.9%) at 12 months. Proportion of patients showing resolution was highest among the stress incontinence group at 96.5%. Presence or absence of comorbidities did not significantly influence the ICIQ-UI-SF scores. Conclusion(s): Bariatric surgery leads to profound improvement in UI in obese individuals which is well sustained until 1 year of follow-up. Resolution rates might be higher in Asian population.Copyright © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Arya, S., et al. (2021). "Metabolic syndrome in obesity: treatment success and adverse pregnancy outcomes with ovulation induction in polycystic ovary syndrome." American Journal of Obstetrics and Gynecology 225(3): 280.e281-280.e211.
	BACKGROUND: Obesity is common in women with polycystic ovary syndrome. polycystic ovary syndrome and obesity are associated with reduced fertility. The effect of metabolic syndrome on the success of infertility treatment and pregnancy outcomes in women with polycystic ovary syndrome undergoing ovulation induction has not been investigated. OBJECTIVE: The objectives of this study were to determine the associations of metabolic syndrome on the rate of live birth after ovulation induction and pregnancy complications in obese women with polycystic ovary syndrome and determine whether there is a difference in outcomes concerning specific medications used for ovulation induction. STUDY DESIGN: This prospective cohort analysis used data collected from participants in the Pregnancy in Polycystic Ovary Syndrome II clinical trial conducted by the Reproductive Medicine Network. In the Pregnancy in Polycystic Ovary Syndrome II trial, 750 women with polycystic ovary syndrome and infertility were randomized to either clomiphene citrate or letrozole for ovulation induction for 1 to 5 cycles or until pregnancy occurred. Cox regression and modified Poisson regression, chi-square test, and Student t test or Wilcoxon test were used in this study. Outcomes of interest were rates of live birth and clinical pregnancy and pregnancy complications. Having metabolic syndrome was defined by the presence of at least 3 of 5 cardiometabolic risk factors (waist circumference of >88 cm, low high-density lipoprotein cholesterol of <50 mg/dL, triglycerides of ≥150 mg/dL, systolic blood pressure of ≥130 or diastolic blood pressure of ≥85 mm Hg, and fasting glucose of >100 mg/dL). In addition, we used a continuous metabolic syndrome z score. Body mass index categories were defined as normal (body mass index of <25 kg/m2), high (25 to 35 kg/m2), and very high (>35 kg/m2). RESULTS: As illustrated in the Table, early pregnancy losses showed no difference by metabolic syndrome. Fewer women achieved a clinical pregnancy (20.5% vs 29.7%; P=.007) or had a live birth (16.5% vs 27%; P=.001) in the presence of metabolic syndrome. Early pregnancy losses showed no difference by metabolic syndrome status. However, at least 1 pregnancy complication occurred more often with metabolic syndrome: 61.9% (26 of 42 cases) with metabolic syndrome vs 44.4% (59 of 133 cases) (P=.05) without metabolic syndrome. Gestational diabetes mellitus (35.7% vs 18.2%; P=.02) and macrosomia (21.4% vs 8.3%; P=.02) were more common in the presence of metabolic syndrome. After adjustment for other potential confounders, the rate ratio for live births for a 1-unit change in the metabolic syndrome z score was 0.89 (95% confidence interval, 0.79-1.00; P=.04) for those whose body mass index was 25 to 35 kg/m2. For the very high body mass index subgroup (>35 kg/m2), the independent effects of metabolic syndrome from obesity were harder to discern. The rate of live birth was higher with the use of letrozole, although metabolic syndrome had a different detrimental effect concerning the medication given. The overall incidence of pregnancy complications was high (approximately 49%) in the Pregnancy in Polycystic Ovary Syndrome II trial and the 2 medications. Letrozole was associated with more obstetrical complications in the presence of metabolic syndrome, and clomiphene was associated with a lower rate of live birth rate when metabolic syndrome was present. CONCLUSION: Metabolic syndrome is a risk factor that lowers the rate of live birth after ovulation for women with polycystic ovary syndrome, independent of obesity, and it is particularly associated with a lower rate of live birth for women using clomiphene compared with women using letrozole. In addition, metabolic syndrome is a risk factor for pregnancy complications for women with obesity using letrozole. Furthermore, having metabolic syndrome is a risk factor for gestational diabetes mellitus and macrosomia.

Asano, H., et al. (2022). "Status of the Current Treatment Options and Potential Future Targets in Uterine Leiomyosarcoma: A Review." Cancers 14(5).
	Uterine leiomyosarcoma (uLMS) is the most common subtype of mesenchymal tumors in the uterus. This review aims to summarize the current standard therapies and the molecular properties of uLMS for novel molecular-targeted therapies. Although 65% of uLMS cases are diagnosed in stage I, the 5-year overall survival rate is less than 60%. The only effective treatment for uLMS is complete and early resection, and chemotherapy is the main treatment for unresectable advanced or recurrent cases. No chemotherapy regimen has surpassed doxorubicin monotherapy as the first-line chemotherapy for unresectable advanced or recurrent cases in terms of overall survival in phase 3 trials. As a second-line treatment, pazopanib, trabectedin, and eribulin are used, but their therapeutic effects are not sufficient, highlighting the urgent need for development of novel treatments. Recent developments in gene analysis have revealed that homologous recombination deficiency (HRD), including breast cancer susceptibility gene 2 ( BRCA2 ) mutations, are frequently observed in uLMS. In preclinical studies and several case series, poly(adenosine diphosphate-ribose)polymerase inhibitors showed antitumor effects on uLMS cell lines with BRCA2 mutations or HRD and in recurrent or persistent cases of uLMS with BRCA2 mutations. Thus, HRD, including BRCA mutations, may be the most promising therapeutic target for uLMS.

Aschenbrenner, D. (2023). "First Oral Treatment for Postpartum Depression." The American journal of nursing 123(12): 16-17.
	
Aschenbrenner Diane, S. (2022). "New Approved Use for Keytruda." The American journal of nursing 122(7): 26-27.
	Pembrolizumab (Keytruda) is now approved as a single agent to treat advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient in those whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aschenbrenner Diane, S. (2022). "New Drug Treats Cervical Cancer." The American journal of nursing 122(1): 21.
	Tisotumab vedotin-tftv (Tivdak) has received accelerated approval to treat adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.Ocular adverse effects occurred in 60% of patients in clinical trials. To minimize this risk, nurses should follow the guidelines for premedication and required eye care. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aschenbrenner Diane, S. (2023). "New Drug Treats Female Reproductive Cancers." The American journal of nursing 123(4): 25.
	Mirvetuximab soravtansine-gynx (Elahere) has been granted accelerated approval to treat adult patients with folate receptor α-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens.The drug's labeling includes a boxed warning for ocular toxicity. Other warnings include a risk of pneumonitis, peripheral neuropathy, and embryo-fetal toxicity. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aschenbrenner Diane, S. (2023). "Second Nonhormonal Drug for Menopausal Hot Flashes." The American journal of nursing 123(11): 22-23.
	Fezolinetant (Veozah) has been approved to treat severe vasomotor symptoms—also called hot flashes—during menopause. Adverse effects of treatment include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevations in hepatic transaminases. Nurses and NPs should confirm that liver function studies are completed at baseline and at three, six, and nine months after starting therapy.

Asgharpoor, M., et al. (2021). "Medicinal plants used in treatment of vaginal atrophy in postmenopausal women: A systematic review." Journal of Mazandaran University of Medical Sciences 30(194): 140-155.
	Background and purpose: Volvovaginal atrophy is a common and progressive complication in menopausal women, affecting their daily life activities, sexual health, and quality of life. Hormone therapy is associated with some problems and many women prefer herbal medicine to reduce the symptoms. This systematic review aimed to explore the effect of medicinal plants on treatment of vaginal atrophy in postmenopausal women Material(s) and Method(s): Electronic databases, including Scopus, Pubmed, Web of Science, Science Direct, SID, Magiran and Google Scholar search engine were searched by two researchers independently. The following keywords were used in English and Persian: Herbal Medicine, Medicinal Plants, vagina, Atrophy, Postmenopausal Period, Clinical Trial, and relevant articles published until December 2020 were selected. The CONSORT 2010 checklist was used to assess the quality of studies and those with score 18 or higher entered this systematic review. Result(s): Out of 747 articles, 12 clinical trials were investigated in current review. These articles studied seven medicinal plants (chamomile, licorice, fennel, Pueraria mirifica, flaxseed, black cohosh, and red clover). Herbal products can have beneficial effects on reducing the symptoms of vaginal atrophy in postmenopausal women. Conclusion(s): Medicinal plants containing phytoestrogens can be considered as a treatment of choice for improving vaginal atrophy and a suitable alternative to chemical drugs following further studies that prove their efficacy.Copyright © 2021, Mazandaran University of Medical Sciences. All rights reserved.

Ashmita, G., et al. (2021). "Comparison on Efficiency of Ginger with NSAIDs and Complementary Therapy in Primary Dysmenorrhea; A Systematic Review."
	
Ashraf, M., et al. (2022). "Menopause, skin and common dermatoses. Part 4: oral disorders." Clinical and experimental dermatology 47(12): 2130-2135.
	The physiological impact of declining oestrogen levels during menopause has been well documented. We conducted a literature review to assess the impact of menopause on oral health. Falling oestrogen levels are associated with adverse effects on the gingival, oral and buccal epithelia. The symptoms prevalent in perimenopausal and postmenopausal women range from dry mouth to immune-mediated mucocutaneous disease and burning mouth syndrome. Our review has highlighted the need for further research into potential treatments for oral symptoms in menopause, particularly with regard to hormone replacement therapy. (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Ashrafizaveh, A., et al. (2019). "Application of Medicinal Plants, Acupuncture, Massage Therapy and Transcutaneous Electric Nerve Stimulation in Treatment of Endometriosis: Review Study." Iranian Journal of Obstetrics, Gynecology and Infertility 22(5): 90-100.
	Introduction: Endometriosis is a common gynecologic problem which can lead to destruction of a woman's life. Some pharmacological techniques and surgical resection are effective in treating endometriosis pain, but are associated with high recurrence rate. This narrative review study was performed with aim to evaluate the efficacy of some complementary therapies on the control of endometriosis complications. Method(s): In this review, the related articles were reviewed by searching the databases such as Pubmed, Cochrane, Scopus, Web of Science, Uptodate, SID, Irandoc, Magiran, and as well as Google Scholar search engine without time limitations up to February 2019. Search was conducted using the keywords of "Endometriosis", "Complementary Therapies", "Acupuncture", "Massage", "Herbal Medicine", "Transcutaneous Electric Nerve Stimulation" and their Persian equivalent. Result(s): According to search strategy, 8702 articles were found in the first stage, ultimately, among them, 12 articles had inclusion criteria to enter the current review. Based on the findings of these studies, the use of acupuncture and herbal medicine have significant effect on the improvement of endometriosis parameters such as pelvic chronic pain, dyspareunia, dysmenorrhea and infertility. In addition, the results of two studies about comparison of herbal medicine and routine chemical drugs used in endometriosis treatment indicated the equality of their effects in reducing pain and improving fertility. The effect of massage therapy and use of transcutaneous electric nerve stimulation on pain management in these patients was confirmed in two separate studies. Conclusion(s): The findings of present study indicate the positive effects of acupuncture, medicinal herbs, massage therapy and transcutaneous electric nerve stimulation in managing the complications of endometriosis. Therefore, the use of these therapeutic approaches and referral of patients to complementary medicine specialists is suggested as one of the most important priorities in the management of endometriosis complications.Copyright © 2019, Mashhad University of Medical Sciences. All rights reserved.

Aslam, B., et al. (2023). "Exploring the potential impact of GLP-1 receptor agonists in cancer therapy." Minerva Endocrinology.
	Glucagon-like peptide-1 (GLP-1) receptor agonists are used in diabetes management and can have a potential application in cancer therapy. While their involvement in cancer treatment is still being studied, recent research suggests they may have benefits in cancer therapy. A comprehensive literature search was conducted using search engines like Google Scholar, Scopus, and PubMed to explore the effects of GLP-1 receptor agonists in tumor suppression and regression. Mostly in-vitro studies on GLP-1 receptor agonists have shown promising effects in inhibiting cancer cell growth, inducing apoptosis, and modulating angiogenesis and have been reported to be beneficial in colon, prostate, gall bladder, ovarian, and endometrial carcinomas. However, concerns have been raised about potential tumorigeneses, as liraglutide has been reported to be associated with increased incidence of breast, thyroid, and pancreatic carcinomas. Whereas combination therapy of exendin-4 with gemcitabine may be beneficial in pancreatic cancer. GLP-1 receptor agonists may have significant potential in oncology, due to their various mechanisms of action and favorable safety profiles. Limited clinical application, lack of awareness, and the need for further research are current barriers. Future studies should focus on optimal dosage, patient selection, and interdisciplinary collaboration to integrate GLP-1 receptor agonists into routine oncological practice for improved outcomes, warranting large randomized clinical trials in this field.

As-Sanie, S., et al. (2022). "RELUGOLIX COMBINATION THERAPY IN NORTH AMERICAN WOMEN WITH ENDOMETRIOSIS-ASSOCIATED PAIN: SPIRIT 1 AND 2 TRIALS." Fertility and Sterility 118(4 Supplement): e223.
	Objective: Once-daily relugolix combination therapy (Rel-CT; relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) significantly improved endometriosis-associated pain in the phase 3 multinational SPIRIT 1 and 2 studies. The present analysis evaluated whether there was a difference in treatment response to Rel-CT over 24 weeks (wks) between the overall and North American (NA) SPIRIT study populations. Material(s) and Method(s): Premenopausal women with moderate-to-severe dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) who enrolled in the SPIRIT 1 and 2 trials were randomized 1:1:1 to receive Rel-CT or placebo for 24 wks, or delayed Rel-CT (relugolix 40 mg monotherapy for 12 wks, followed by Rel-CT for 12 wks). Randomization ratio remained balanced when stratified by region (NA vs Rest of World). Coprimary endpoints were the proportion of DYS and NMPP responders at Wk 24, based on daily patient-reported Numerical Rating Scale (NRS) scores (0=no pain, 10=worst pain imaginable). Responders were women who achieved a predefined, clinically meaningful reduction from baseline in NRS score and no increase in analgesic use. Demographics and baseline characteristics were summarized descriptively. Estimated odds ratio and 95% confidence interval (OR, 95% CI) were calculated for DYS and NMPP; a value > 1 favors Rel-CT over placebo. Adverse events (AEs) and bone mineral density (BMD) were summarized descriptively. Result(s): Of 1261 women randomized in SPIRIT 1/2, 1251 were included in the analyses; of these, 270 enrolled from NA. Mean age (years) was similar in the NA (32.2) and overall (33.9) populations. The NA cohort demographics had a higher proportion of Black/African American (21.5%) and Hispanic/Latino women (21.5%) vs the overall population (5.7% and 11.9%, respectively). Mean [SD] body mass index was higher in the NA (29.8 [7.4]) vs overall (25.9 [6.1]) population. Baseline characteristics were generally similar between the NA and overall populations: time since surgical diagnosis (4.1 [3.1] and 4.0 [3.4] years); mean NRS scores for DYS (7.2 [1.8] and 7.0 [1.6]), NMPP (5.7 [2.2] and 5.7 [1.9]) and dyspareunia (5.7 [2.6] and 5.5 [2.3]). While the proportion of opioid users was modestly higher in the NA (43.3%) vs overall (38.4%) population, the proportion of current smokers was similar (~18.5%). At Wk 24, a significantly higher proportion of women in the Rel-CT vs placebo group met the definition for responder in both NA and overall populations: OR (95% CI) for DYS [NA: 5.93 (2.96, 11.87) vs overall: 8.15 (5.92, 11.23)] and NMPP [NA: 2.19 (1.15, 4.16) vs overall: 2.44 (1.83, 3.24)]. Rates of AEs were generally similar in NA (67%) and overall populations (75%). Mean percent change from baseline in BMD at the lumbar spine at Wk 24 for Rel-CT and placebo was similar: NA: -0.85% and 0.12% and overall: -0.72% vs 0.12%, respectively. Conclusion(s): Treatment effect of Rel-CT in the NA subgroup was consistent with that seen in the SPIRIT overall population. Impact Statement: Consistency of outcomes between NA and overall SPIRIT populations support generalizability of overall results for NA women with endometriosis-associated pain.Copyright © 2022

Assis, G. M., et al. (2019). "Urotherapy in the treatment of children and adolescents with bladder and bowel dysfunction: a systematic review." Jornal de pediatria 95(6): 628-641.
	OBJECTIVE: To identify and describe the protocols and clinical outcomes of urotherapy interventions in children and adolescents with bladder bowel dysfunction. METHOD: Systematic review carried out in June 2018 on MEDLINE/PubMed, CINAHL, EMBASE, SciELO, Cochrane, and PsycInfo databases. Clinical trials and quasi-experimental studies carried out in the last ten years in children and/or adolescents with bladder and bowel symptoms and application of at least one component of urotherapy were included. RESULTS: Thirteen clinical trials and one quasi-experimental study were included, with moderate methodological quality. The heterogeneity of the samples and of the methodological design of the articles prevented the performance of a meta-analysis. The descriptive analysis through simple percentages showed symptom reduction and improvement of uroflowmetry parameters. The identified urotherapy components were: educational guidance, water intake, caffeine reduction, adequate voiding position, pelvic floor training, programmed urination, and constipation control/management. CONCLUSION: This review indicates positive results in terms of symptom reduction and uroflowmetry parameter improvement with standard urotherapy as the first line of treatment for children and adolescents with bladder bowel dysfunction. It is recommended that future studies bring contributions regarding the frequency, number, and time of urotherapy consultations.

Astasio-Picado, A. and M. Garcia-Cano (2022). "Neuromodulation of the Posterior Tibial Nerve for the Control of Urinary Incontinence." Medicina (Kaunas, Lithuania) 58(3).
	Urinary incontinence is considered a health problem that both elderly and young people can suffer, most often elderly women. This problem can lead to difficulties in establishing social relationships and dependence, negatively affecting the quality of life of the people who suffer from it. To evaluate and analyze the studies that demonstrate the efficacy of interventions based on the neuromodulation of the posterior tibial nerve as a treatment for the control of urinary incontinence. The search period for articles focused on those published between March 2011 to March 2021, in five databases (Pubmed, Cochrane Library, Scielo, Google Academic and WOS) based on the clinical question, using the keywords derived from the DeCS and MeSH thesauri, combined with the Boolean operators "AND", "NOT" and "OR". The search was limited to publications from the last 10 years, in English and Spanish. After applying the selection criteria and evaluating the quality of the methodology, 5.28% (n = 27) of the 511 results were included with filters: 9 systematic reviews, 10 cohorts and 8 randomized controlled trials. After comparing the different articles, it was found that percutaneous stimulation of the tibial nerve is a suitable technique for treating overactive bladder. It is a promising technique in case of pelvic floor dysfunctions and effective for the control of urinary incontinence.

Astellas Pharma Global Development, I. and P. Inc Astellas (2021). A Study of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause.
	No Results Available Drug: fezolinetant|Drug: placebo Mean change in the frequency of moderate to severe Vasomotor Symptoms (VMS) from baseline to week 24|Mean change in the severity of moderate to severe VMS from baseline to week 24|Mean change in the patient-reported sleep disturbance by the PROMIS SD SF 8b total score from baseline to week 24|Mean change in the frequency of moderate to severe VMS|Mean change in the severity of moderate to severe VMS|Mean percent change in the frequency of moderate and severe VMS|Percent reduction ≥ 50% in the frequency of moderate and severe VMS|Percent reduction ≥ 75% in the frequency of moderate and severe VMS|Percent reduction at 100% in the frequency of moderate and severe VMS|Number of participants with Treatment Emergent Adverse Events (TEAEs)|Number of participants with laboratory value abnormalities and/or adverse events (AEs)|Number of participants with vital sign abnormalities and/or adverse events (AEs)|Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) Female Phase 3 453 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment 2693-CL-0312|2021-001685-38 April 20, 2023

Astellas Pharma Global Development, I. and P. Inc Astellas (2022). Study of ASP0739 Alone and With Pembrolizumab in Advanced Solid Tumors With NY-ESO-1 Expression Participants.
	No Results Available Drug: ASP0739|Drug: Pembrolizumab Incidence of Dose Limiting Toxicities (DLTs) for ASP0739 Single Agent|Incidence of Dose Limiting Toxicities (DLTs) for ASP0739 + Pembrolizumab Safety Lead-in|Number of Participants with adverse events (AEs)|Number of Participants with Serious Adverse Events (SAEs)|Number of participants with laboratory value abnormalities and/or AEs|Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs|Number of participants with vital sign abnormalities and/or AEs|Number of participants with physical exam abnormalities and/or AEs|Number of participants at each grade of the Eastern Cooperative Oncology Group (ECOG) performance status|Objective Response Rate per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR) by Independent Central Review|Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1|Disease Control Rate per iRECIST (iDCR)|Disease Control Rate per RECIST v1.1 (DCR)|Progression-Free Survival per iRECIST (iPFS) by Independent Central Review|iPFS per iRECIST by local assessment|Progression-Free Survival per RECIST v1.1 (PFS) by Independent Central Review|PFS per RECIST v1.1 by local assessment|Duration of Overall Survival (OS)|Duration of Response per iRECIST (iDOR) by Independent Central Review|iDOR per iRECIST by local assessment|Duration of Response per RECIST (DOR) v1.1 by Independent Central Review|DOR per RECIST v1.1 by local assessment|ORR per iRECIST (iORR) by local assessment All Phase 1|Phase 2 16 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 0739-CL-0101 June 1, 2023

AstraZeneca (2021). First in Human Study to Evaluate AZD8205 in Patients With Advanced or Metastatic Solid Malignancies.
	This study is a Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination with Anticancer Agents in Participants with Advanced Solid Tumors

AstraZeneca, et al. (2023). Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical).
	No Results Available Biological: Volrustomig|Other: Placebo Progression-free Survival (PFS) in participants with PD-L1 expression based on the investigator assessment|Progression-free Survival (PFS) in participants regardless of PD-L1 expression based on the investigator assessment|Overall Survival (OS) in participants regardless of PD-L1 expression.|Overall Survival (OS) in participants with PD-L1 expression|Objective Response Rate (ORR) in participants with PD-L1 expression/regardless of PD-L1 expression.|Duration of Response (DoR) in participants with a CR or PR in the PD-L1 expression analysis set/FAS.|Time to First Subsequent Therapy or death (TFST) in the PD-L1 expression analysis set/FAS|Time to second progression or death (PFS2) in the PD-L1 expression analysis set/FAS.|PFS by BICR in the PD-L1 expression analysis set/FAS.|The incidence of local progression, and distant disease progression as the first documented progression event in the PD-L1 expression analysis set/FAS.|PK of Volrustomig|The immunogenicity of volrustomig.|Incidence of adverse events of Volrustomig compared to placebo;|Participant-reported disease-related symptoms|Participant-reported physical functioning|Participant-reported global health status/Quality of Life. Female Phase 3 1000 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment D7984C00002|GOG-3092|ENGOT-cx19/GEICO|165663|2023-504374-38-00 October 24, 2029

Astrid, K., et al. (2023). "Psychiatric treatments for premenstrual syndrome and premenstrual dysphoric disorder – a systematic review and meta-analysis."
	
Ata, B., et al. (2021). "Progestins for pituitary suppression during ovarian stimulation for ART: a comprehensive and systematic review including meta-analyses." Human Reproduction Update 27(1): 48-66.
	Background: Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression.; Objective and Rationale: This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified.; Search Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included.; Outcomes: Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = -648, 95% CI = -746 to -550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET.; Wider Implications: Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ata, B. and E. Kalafat (2024). "Progestin-primed ovarian stimulation: for whom, when and how?" Reproductive Biomedicine Online 48(2): 103639.
	Progestin-primed ovarian stimulation (PPOS) is being increasingly used for ovarian stimulation in assisted reproductive technology. Different progestins have been used with similar success. The available studies suggest a similar response to ovarian stimulation with gonadotrophin-releasing hormone (GnRH) analogues. Any differences in the duration of stimulation or gonadotrophin consumption are minor and clinically insignificant. PPOS has the advantage of oral administration and lower medication costs than GnRH analogues. As such it is clearly more cost-effective for fertility preservation and planned freeze-all cycles, but when fresh embryo transfer is intended PPOS can be less cost-effective depending on the local direct and indirect costs of the additional initial frozen embryo transfer cycle. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analogue cycles seem to be similar in terms of both ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies have reported lower cumulative live birth rates with PPOS, they have methodological issues, including arbitrary definitions of the cumulative live birth rate. PPOS has been used in all patient types (except progesterone receptor-positive breast cancer patients) with consistent results and seems a patient friendly and cost-effective choice if a fresh embryo transfer is not intended.Copyright © 2023 Reproductive Healthcare Ltd.

Atak, Z., et al. (2023). "Levonorgestrel-releasing intrauterine device to treat abnormal uterine bleeding; not one treatment option fits all." Journal of the Turkish German Gynecological Association 24(4): 246-251.
	Objective: Initially, medical treatment options are preferred in patients with abnormal uterine bleeding (AUB) who are hemodynamically stable. The aim of the present study was to investigate the effectiveness of a levonorgestrel-releasing intrauterine device (LNG-IUD) in reducing bleeding symptoms in patients with AUB stratified by underlying pathology.; Material and Methods: In line with the polyp, adenomyosis, leiomyoma, malignancy (and hyperplasia), coagulopathy, ovulatory disorders, endometrial, iatrogenic and not otherwise classified classification system, patients who were administered LNG-IUD due to adenomyosis, endometrial hyperplasia, leiomyoma and AUB due to not otherwise classified causes were included in the study.; Results: A total of 172 otherwise patients with a mean age of 42.58±5.00 years were included. The distributions in the adenomyosis, endometrial hyperplasia, leiomyoma and otherwise unclassified groups were 30.8%, 12.8%, 26.2%, and 30.2%, respectively. Overall effectiveness of LNG-IUD in reducing menstrual bleeding was 82%. The proportion whose bleeding decreased was 95.50% in the endometrial hyperplasia group, 88.70% in the adenomyosis group, 55.60% in the leiomyoma group and 92.30% in the not otherwise classified group. The power of the current study was 99%. The efficacy of LNG-IUD was significantly less in the leiomyoma group (p<0.05) and thus this group were more likely to require surgical intervention. The overall incidence of spotting was 50%. Amenorrhea developed in 14% of patients.; Conclusion: While LNG-IUD was more effective in reducing symptoms of AUB in patients with adenomyosis, endometrial hyperplasia and not otherwise classified causes, LNG-IUD was less effective in cases of leiomyoma.; Competing Interests: Conflict of Interest: No conflict of interest is declared by the authors. (©Copyright 2023 by the Turkish-German Gynecological Education and Research Foundation. Journal of the Turkish-German Gynecological Association is published by Galenos Publishing House.)

Athanasiou, A., et al. (2022). "Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis." The Lancet. Oncology 23(8): 1097-1108.
	Background: The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques.; Methods: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508.; Findings: 7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44-0·79] and CKC: 0·63 [0·50-0·81]) and increased for laser ablation (1·69 [1·27-2·24]) and cryotherapy (1·84 [1·33-2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68-1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70-3·02]; laser conisation: 1·77 [1·29-2·43]; and LLETZ: 1·37 [1·16-1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78-1·41]; cryotherapy: 1·01 [0·35-2·92]; and cold coagulation: 0·67 [0·02-29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low.; Interpretation: More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning.; Funding: National Institute for Health and Care Research: Research for Patient Benefit.; Competing Interests: Declaration of interests OE has received consulting fees from Biogen (payments were made to their University). All other authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Athanasiou, A., et al. (2019). "Comparative fertility and pregnancy outcomes after local treatment for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: protocol for a systematic review and network meta-analysis from the CIRCLE group." BMJ Open 9(10): e028009.
	Introduction: There are several local treatment methods for cervical intraepithelial neoplasia that remove or ablate a cone-shaped part of the uterine cervix. There is evidence to suggest that these increase the risk of preterm birth (PTB) and that this is higher for techniques that remove larger parts of the cervix, although the data are conflicting. We present a protocol for a systematic review and network meta-analysis (NMA) that will update the evidence and compare all treatments in terms of fertility and pregnancy complications.; Methods and Analysis: We will search electronic databases (CENTRAL, MEDLINE, EMBASE) from inception till October 2019, in order to identify randomised controlled trials (RCTs) and cohort studies comparing the fertility and pregnancy outcomes among different excisional and ablative treatment techniques and/or to untreated controls. The primary outcome will be PTB (<37 weeks). Secondary outcomes will include severe or extreme PTB, prelabour rupture of membranes, low birth weight (<2500 g), neonatal intensive care unit admission, perinatal mortality, total pregnancy rates, first and second trimester miscarriage. We will search for published and unpublished studies in electronic databases, trial registries and we will hand-search references of published papers. We will assess the risk of bias in RCTs and cohort studies using tools developed by the Cochrane collaboration. Two investigators will independently assess the eligibility, abstract the data and assess the risk of bias of the identified studies. For each outcome, we will perform a meta-analysis for each treatment comparison and an NMA once the transitivity assumption holds, using the OR for dichotomous data. We will use CINeMA (Confidence in Network meta-analysis) to assess the quality of the evidence for the primary outcome.; Ethics and Dissemination: Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.; Prospero Registration Number: CRD42018115495.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Athanasiou, S., et al. (2020). "Intravaginal energy-based devices and sexual health of female cancer survivors: a systematic review and meta-analysis." Lasers in Medical Science 35(1): 1-11.
	A systematic review and meta-analysis was undertaken to assess the efficacy and safety of intravaginal energy-based therapies (laser and radiofrequency) on sexual health of cancer survivors (CS) (breast cancer (BCS) and/or gynecological cancer (GCS)). PubMed, Scopus, Web of Science, and Cochrane Library were searched until 21/02/2019. Quality of reporting, methodology, and body of evidence were assessed using STROBE, MINORS, and GRADE. Primary outcomes were dyspareunia, dryness, and sexual health (FSFI, FSDS-R). Secondary outcomes were burning, itching, dysuria, incontinence, Vaginal Health Index Score (VHIS), microbiome-cytokine evaluation, and adverse events. Main analyses, subgroup analyses, and sensitivity analyses were performed. Eight observational studies (n = 274) were eligible for inclusion. None of the studies evaluated radiofrequency. BCS and BCS-GCS were included in 87% and 13% of studies, respectively. All primary outcomes improved significantly with the exception of FSDS-R (dyspareunia (5 studies (n = 233), standardized mean difference (StdMD) (- 1.17), 95%CI [- 1.59, - 0.75]; p < 0.001; I 2 = 55%), vaginal dryness (4 studies (n = 183), StdMD (- 1.98), 95%CI [- 3.31, - 0.65]; p = 0.003; I 2 = 91%), FSFI (2 studies, n = 28, MD (12.79), 95%CI [7.69, 17.89]; p < 0.001; I 2 = 0%). Itching, dysuria, and VHIS increased significantly, while burning was not improved. Serious adverse events were not observed by any of the studies. Intravaginal laser therapies appear to have a positive effect on dyspareunia, vaginal dryness, and FSFI of CS. However, the quality of evidence is "very low," with no data on intravaginal radiofrequency therapy. Further research with high-quality RCTs and long-term follow-up is needed to evaluate the value of energy-based devices as a therapeutic option for CS with sexual problems.

Athanasiou, S., et al. (2020). "A study protocol of vaginal laser therapy in gynecological cancer survivors." Climacteric : the journal of the International Menopause Society 23(1): 53-58.
	Objectives: Sexual dysfunction and radiation cystitis are common adverse events following radiotherapy for gynecological cancer (GC). This study aims to assess the efficacy of intravaginal CO 2 laser on GC survivors with dyspareunia following pelvic radiation and/or brachytherapy. Methods: This is the study protocol of a randomized double-blind placebo-controlled trial. All participants will receive five therapies (active or placebo) at monthly intervals. Outcomes will include a 10-cm visual analog scale measuring dyspareunia, vaginal dryness, and other symptom intensity, 3-day voiding diary, Day-to Day Impact of Vaginal Aging questionnaire, Female Sexual Function Index, European Organization for Research and Treatment of Cancer Quality of Life questionnaire cervical cancer module, Urogenital Distress Inventory short form, King's Health Questionnaire, International Consultation on Incontinence Questionnaire short form/female lower urinary tract symptoms, patient perception of improvement, sexual satisfaction of male partners, vaginal maturation value, and Vaginal Health Index. Differences between groups will be assessed at baseline and 1, 3, 6, 9, and 12 months following the five laser therapies. Results: As this is a study protocol, the study is ongoing with an expected end of recruitment and analysis date of 2021. Conclusion: Pelvic radiotherapy for GC increases the 5-year survival rate but with a negative impact on women's quality of life due to sexual dysfunction and radiation cystitis onset. With this study, CO 2 laser therapy will be evaluated for the first time in GC survivors treated with radiotherapy. ClinicalTrials.gov registration number: NCT03714581.

Atılgan, A. E. and A. Aydın (2021). "Cystocele Repair with Platelet-Rich Plasma." Indian journal of surgery 83(3): 726‐730.
	
Atkinson, A., et al. (2022). "Systematic review of randomized control trials into effective preoperative weight loss interventions and impact on surgical outcomes for major benign gynecological surgery." Journal of Obstetrics and Gynaecology Research 48(8): 2093-2099.
	Aims: Limited information exists on what preoperative weight loss interventions (lifestyle, pharmacological, surgical) are effective in improving outcomes of elective, nononcological, gynecological surgery. Obesity rates are increasing and associated with poorer operative outcomes. We aimed to identify high quality studies into preoperative weight loss interventions and perform a systematic review of the literature to guide recommendations for reducing gynecological surgical complications and guide future research. Primary outcomes were mortality and surgical complications including conversion to open surgery, duration of surgery, and recovery. Method(s): The review was pre-registered with PROPSERO. A systematic search was undertaken of the major electronic bibliographic databases. Search results were compiled and abstracts of studies identified before application of the Cochrane highly sensitive search strategy (CHSSS) were reviewed. Full text of studies after application of the CHSSS were evaluated for suitability. For data collection and analysis, a minimum three high-quality randomized control trials were required to synthesize data in relation to the primary outcome. Result(s): No trials met the inclusion criteria. No randomized control trials in gynecological cohorts were identified. Studies in gynecology-oncology were excluded due to the confounding nature of weight loss as a feature of illness as opposed to health optimization. Conclusion(s): There is limited evidence regarding preoperative weight loss interventions in gynecology. Further research is needed as the prevalence of obesity among women is increasing and definitive surgical management options in gynecology remain essential. PROSPERO registration ID: 165643.Copyright © 2022 Japan Society of Obstetrics and Gynecology.

Attama, A. A., et al. (2022). "Nanogels as target drug delivery systems in cancer therapy: A review of the last decade." Frontiers in Pharmacology 13: 874510.
	Cancer is an important cause of morbidity and mortality worldwide, irrespective of the level of human development. Globally, it was estimated that there were 19.3 million new cases of cancer and almost 10 million deaths from cancer in 2020. The importance of prevention, early detection as well as effective cancer therapies cannot be over-emphasized. One of the important strategies in cancer therapy is targeted drug delivery to the specific tumor sites. Nanogels are among the several drug delivery systems (DDS) being explored as potential candidates for targeted drug delivery in cancer therapy. Nanogels, which are new generation, versatile DDS with the possession of dual characteristics of hydrogels and nanoparticles have shown great potential as targeted DDS in cancer therapy. Nanogels are hydrogels with a three-dimensional (3D) tunable porous structure and a particle size in the nanometre range, from 20 to 200 nm. They have been visualized as ideal DDS with enormous drug loading capacity, and high stability. Nanogels can be modified to achieve active targeting and enhance drug accumulation in disease sites. They can be designed to be stimulus-responsive, and react to internal or external stimuli such as pH, temperature, light, redox, thus resulting in the controlled release of loaded drug. This prevents drug accumulation in non-target tissues and minimizes the side effects of the drug. Drugs with severe adverse effects, short circulation half-life, and easy degradability by enzymes, such as anti-cancer drugs, and proteins, are suitable for delivery by chemically cross-linked or physically assembled nanogel systems. This systematic review summarizes the evolution of nanogels for targeted drug delivery for cancer therapy over the last decade. On-going clinical trials and recent applications of nanogels as targeted DDS for cancer therapy will be discussed in detail. The review will be concluded with discussions on safety and regulatory considerations as well as future research prospects of nanogel-targeted drug delivery for cancer therapy.Copyright © 2022 Attama, Nnamani, Onokala, Ugwu and Onugwu.

Attanasio Laura, B., et al. (2022). "Postpartum visit attendance in the United States: A systematic review." Women's Health Issues 32(4): 369-375.
	Introduction: Adequate postpartum care, including the comprehensive postpartum visit, is critical for long-term maternal health and the reduction of maternal mortality, particularly for people who may lose insurance coverage postpartum. However, variation in previous estimates of postpartum visit attendance in the United States makes it difficult to assess rates of attendance and associated characteristics. Methods: We conducted a systematic review of estimates of postpartum visit attendance. We searched PubMed, CINAHL, PsycInfo, and Web of Science for articles published in English from 1995 to 2020 using search terms to capture postpartum visit attendance and use in the United States. Results: Eighty-eight studies were included in this analysis. Postpartum visit attendance rates varied substantially, from 24.9% to 96.5%, with a mean of 72.1%. Postpartum visit attendance rates were higher in studies using patient self-report than those using administrative data. The number of articles including an estimate of postpartum visit attendance increased considerably over the study period; the majority were published in 2015 or later. Conclusions: Our findings suggest that increased systematic data collection efforts aligned with postpartum care guidelines and attention to postpartum visit attendance rates may help to target policies to improve maternal wellbeing. Most estimates indicate that a substantial proportion of women do not attend at least one postpartum visit, potentially contributing to maternal morbidity as well as preventing a smooth transition to future well-woman care. Estimates of current postpartum visit attendance are important for informing efforts that seek to increase postpartum visit attendance rates and to improve the quality of care. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Attawet, J., et al. (2022). "Pregnancy and birth outcomes of single versus multiple embryo transfer in gestational surrogacy arrangements: a systematic review and meta-analysis." Human fertility (Cambridge, England) 25(2): 217-227.
	Multiple embryo transfer (MET) is associated with both an increased risk of multiple pregnancy and of live birth. In recent years, MET has become standard practice for most surrogacy arrangements. There is limited review of the use of MET versus single embryo transfer (SET) in surrogacy practice. The present review systematically evaluated the pregnancy outcomes of surrogacy arrangements between MET versus SET among gestational carriers. A systematic search of five computerized databases without restriction to the English language or study type was conducted to evaluate the primary outcomes: (i) clinical pregnancy; (ii) live delivery; and (iii) multiple delivery rates. The search returned 97 articles, five of which met the inclusion criteria. The results showed that clinical pregnancy (RR = 1.21, 95% CI: 1.06-1.39, n = 5, I 2 = 41%), live delivery (RR = 1.29, 95% CI: 1.10-1.51, n = 4, I 2 = 35%) and multiple delivery rates (RR = 1.42, 95% CI: 6.58-69.73, n = 4, I 2 = 54%) were statistically significantly different in MET compared to SET. Adverse events including miscarriage, preterm birth and low birthweight were found following MET. Our findings support the existing evidence that MET results in multiple pregnancy and subsequently more adverse outcomes compared to SET. From a public health perspective, SET should be advocated as the preferred treatment for gestational carriers.

Aue-Aungkul, A., et al. (2021). "Postoperative interventions for preventing bladder dysfunction after radical hysterectomy in women with early-stage cervical cancer." The Cochrane Database of Systematic Reviews 1: CD012863.
	Background: Bladder dysfunction is a common complication following radical hysterectomy, caused by the damage to pelvic autonomic nerves that innervate the muscles of the bladder, urethral sphincter, and pelvic floor fasciae. Bladder dysfunction increases the rates of urinary tract infection, hospital visits or admission, and patient dissatisfaction. In addition, bladder dysfunction can also negatively impact patient quality of life (QoL). Several postoperative interventions have been proposed to prevent bladder dysfunction following radical hysterectomy. To our knowledge, there has been no systematic review evaluating the effectiveness and safety of these interventions for preventing bladder dysfunction following radical hysterectomy in women with cervical cancer.; Objectives: To evaluate the effectiveness and safety of postoperative interventions for preventing bladder dysfunction following radical hysterectomy in women with early-stage cervical cancer (stage IA2 to IIA2).; Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to April week 2, 2020), and Embase via Ovid (1980 to 2020, week 16). We also checked registers of clinical trials, grey literature, conference reports, and citation lists of included studies.; Selection Criteria: We included randomised controlled trials (RCTs) evaluating the effectiveness and safety of any type of postoperative interventions for preventing bladder dysfunction following a radical hysterectomy in women with stage IA2 to IIA2 cervical cancer.; Data Collection and Analysis: Two review authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, compared results, and made judgments on the quality and certainty of the evidence. We resolved any disagreements through discussion or consultation with a third review author. Outcomes of interest consisted of spontaneous voiding recovery one week after the operation, quality of life (QoL), adverse events, post-void residual urine volume one month after the operation, urinary tract infection over the one month following the operation, and subjective urinary symptoms.; Main Results: We identified 1464 records as a result of the search (excluding duplicates). Of the 20 records that potentially met the review criteria, we included five reports of four studies. Most of the studies had unclear risks of selection and reporting biases. Of the four studies, one compared bethanechol versus placebo and three studies compared suprapubic catheterisation with intermittent self-catheterisation. We identified two ongoing studies. Bethanechol versus placebo The study reported no information on the rate of spontaneous voiding recovery at one week following the operation, QoL, adverse events, urinary tract infection in the first month after surgery, and subjective urinary symptoms for this comparison. The volume of post-void residual urine, assessed at one month after surgery, among women receiving bethanechol was lower than those in the placebo group (mean difference (MD) -37.4 mL, 95% confidence interval (CI) -60.35 to -14.45; one study, 39 participants; very-low certainty evidence). Suprapubic catheterisation versus intermittent self-catheterisation The studies reported no information on the rate of spontaneous voiding recovery at one week and post-void residual urine volume at one month following the operation for this comparison. There was no difference in risks of acute complication (risk ratio (RR) 0.77, 95% CI 0.24 to 2.49; one study, 71 participants; very low certainty evidence) and urinary tract infections during the first month after surgery (RR 0.77, 95% CI 0.53 to 1.13; two studies, 95 participants; very- low certainty evidence) between participants who underwent suprapubic catheterisation and those who underwent intermittent self-catheterisation. Available data were insufficient to calculate the relative measures of the effect of interventions on QoL and subjective urinary symptoms.; Authors' Conclusions: None of the included studies reported rate of spontaneous voiding recovery one week after surgery, time to a post-void residual volume of urine of 50 mL or less, or post-void residual urine volume at 6 and 12 months after surgery, all of which are important outcomes for assessing postoperative bladder dysfunction. Limited evidence suggested that bethanechol may minimise the risk of bladder dysfunction after radical hysterectomy by lowering post-void residual urine volume. The certainty of this evidence, however, was very low. The effectiveness of different types of postoperative urinary catheterisation (suprapubic and intermittent self-catheterisation) remain unproven. (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Auer Rebecca, C., et al. (2020). "Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review." European journal of cancer (Oxford, England : 1990) 127: 76-95.
	The purpose of the present review was to describe evidence-based indications for hyperthermic intraperitoneal chemotherapy (HIPEC), with cytoreductive surgery (CRS), in patients with a diagnosis of mesothelioma, appendiceal (including appendiceal mucinous neoplasm), colorectal, gastric, ovarian or primary peritoneal carcinoma. Relevant studies were identified from a systematic MEDLINE and EMBASE search of studies published from 1985 to 2019. Studies were included if they were RCTs. If no RCTs were identified, prospective and retrospecctive comparative studies (where confounders are controlled for studies with greater than 30 patients) were included. Overall survival, progression-free survival, recurrence-free survival, adverse events and quality of life data were extracted. For patients with newly diagnosed, primary stage III epithelial ovarian, fallopian tube or primary peritoneal carcinoma, HIPEC with CRS should be considered for those with at least stable disease following neoadjuvant chemotherapy at the time of interval CRS if complete or optimal cytoreduction is achieved. There is insufficient evidence to recommend the addition of HIPEC when primary CRS is performed for patients with newly diagnosed, primary advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma or in those with recurrent ovarian cancer outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of peritoneal colorectal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of gastric peritoneal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS in patients with malignant peritoneal mesothelioma or in those with disseminated mucinous neoplasm in the appendix as a standard of care; however, these patients should be referred to HIPEC specialty centres for assessment for treatment as part of an ongoing research protocol.; Competing Interests: Conflict of interest statement None declared. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Augoulea, A., et al. (2021). "Assessing the efficacy of a structured stress management program in reducing stress and climacteric symptoms in peri- and postmenopausal women." Archives of Women's Mental Health 24(5): 727‐735.
	To evaluate the effectiveness of a structured education program on lifestyle habits, which is also incorporating teaching on deep breathing, progressive muscle relaxation, and guided visualization, in the control of various components of the climacteric symptomatology in peri‐ and postmenopausal women. Sixty‐one women aged 40–65 years with varying climacteric and stress symptoms were included in this study. Women were randomly assigned to the intervention group (31) or the control group (30). The intervention group followed an 8‐week stress management program. The following parameters were assessed at baseline and at the end of the 8‐week follow‐up period in both groups: climacteric symptoms (Green Climacteric Scale (GCS)), sleep quality (Pittsburg Sleep Quality Index (PSQI)), mood status (Depression‐Anxiety‐Stress Scale), self‐esteem (Rosenberg Self‐esteem Scale), and health‐related control (health locus of control (HLC)). A mixed‐model ANOVA showed significant time × group × GCS interaction (within subjects: F = 23.830, p value<0.001; between subjects: F = 39.078, p value<0.001). With regard to HLC, there was a non‐significant between subjects but a significant within‐subjects effect (HLC × group × time, F = 3.848, p value = 0.024). Regarding DASS scores, there was a significant between‐subjects’ effect (F = 10.258, p value = 0.003) but a non‐significant within‐subjects’ effect. With regard to PSQI, the analysis showed significant within‐subjects’ effects (PSQI × group × time: F = 4.691, p value = 0.003) and non‐significant between‐subjects’ effects (F = 0.022, p = 0.883). Finally, regarding RSS, there was a significant within‐subjects’ (RSS × group × time, F = 4.183, p value = 0.029) but non‐significant between‐subjects’ effect (F = 1.582, p value = 0.213). Stress management may offer an alternative approach to the management of climacteric symptoms.

Austin, M. N., et al. (2022). "Impact of Dapivirine and Placebo Vaginal Rings on the Microbiota of Adolescent, Lactating, and Postmenopausal Females." Journal of Infectious Diseases 225(12): 2208-2218.
	Background: A 25-mg dapivirine vaginal ring has been demonstrated to reduce risk of human immunodeficiency virus (HIV) acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users. Method(s): Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent criteria, quantitative culture, and quantitative polymerase chain reaction. Result(s): Vaginal ring use did not impact bacterial vaginosis prevalence among the 3 populations and was associated with minimal shifts in microbiota. Adolescents in both arms demonstrated an increased prevalence of Lactobacillus crispatus and a decrease in quantity of Megasphaera lornae. Postmenopausal active and placebo ring users demonstrated an increased prevalence of lactobacilli and non-albicans yeast, while dapivirine ring users demonstrated an increased prevalence of Candida albicans and increased quantity of group B Streptococcus and non-albicans yeasts. Prevotella species were increased in lactating women, whereas Prevotella timonensis increased in prevalence and concentration among adolescent and postmenopausal females and Prevotella bivia increased in prevalence among adolescent dapivirine ring users. Conclusion(s): Dapivirine vaginal ring use was associated with minimal changes in the vaginal microbiota that are likely not clinically significant.Copyright © 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Averbuch, S., et al. (2022). "Pregnancy Reverses Abdominoplasty Aesthetic Outcome: Myth or Misconception? A Cross-Sectional Study." Aesthetic surgery journal 42(1): NP20-NP26.
	Background: The common recommendation for female abdominoplasty candidates is to conclude family planning before undergoing the procedure. However, no evidence demonstrates a correlation between aesthetic outcome compromise, risk for fetal complications, or risk for maternal complications when abdominoplasty is followed by pregnancy.; Objectives: The aim of this study was to evaluate maternal, fetal, and aesthetic outcomes among pregnant females with a history of abdominoplasty.; Methods: The authors conducted an online survey among women who became pregnant after having an abdominoplasty. Participants were recruited via social media groups related to abdominoplasty. The survey included demographic-, aesthetic outcome-, and pregnancy-related questions utilizing a score from 1 (no effect) to 10 (worst effect) to assess abdominal aesthetic outcome compromise.; Results: Thirty-two participants completed the online survey, 15 (46.8%) of which reported their pregnancy was unplanned. Pregnancy-related findings included 5 (15.6%) late premature births (between gestational week 35 and 37), 1 miscarriage, and 1 emergency C-section. Compromised aesthetic outcomes following pregnancy included new abdominal stretch marks (50%, N = 16), widened abdominoplasty scar (28%, N = 9), abdominal skin excess (37.5%, N = 12), and abdominal bulge (25.8%, N = 8). A new hernia was reported by 2 participants (6.3%). The average abdominal aesthetic severity score was 2.7 (range, 1-8), and only 3 scores were above 5 (9.3%). Two women (6.2%) underwent abdominoplasty revision, and 18 (56.2%) stated they would recommend others to undergo abdominoplasty before pregnancy (56.3%).; Conclusions: This survey shows there is room to reevaluate whether future pregnancy should be considered a relative contraindication for undergoing abdominoplasty. (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Avery, J., et al. (2020). "Polycystic ovary syndrome support groups and their role in awareness, advocacy and peer support: A systematic search and narrative review." Current Opinion in Endocrine and Metabolic Research 12: 98-104.
	Polycystic ovary syndrome (PCOS) is a common and distressing condition in which women often lack adequate support and information to achieve the best health and well-being outcomes. PCOS support groups provide evidence-based information, provide peer support, raise awareness and advocate for woman-centred care. We summarise recent evidence and provide reflections from PCOS support group leaders. Women seek and receive information, as well as emotional and social support, from support groups. They report benefits such as confidence to manage the condition, having greater agency in their healthcare. Some support groups have long-standing partnerships with healthcare providers and researchers, making substantial contributions to advocacy and raising awareness. Major opportunities exist for healthcare providers, professional societies and support groups to collaborate, improving the availability of evidence-based information through support groups.Copyright © 2020 Elsevier Ltd

Avila, P. M., et al. (2022). "Emergency department frequentation and unscheduled readmissions within the first year after liver transplantation, and their impact on survival." Revista Espanola de Enfermedades Digestivas 114(5): 266-271.
	The aim of this study was to assess emergency room frequentation, visit causes, and unscheduled readmissions within the first year after discharge from hospital following liver transplantation. Their impact on graft and patient survival was also assessed. This was a retrospective study of the medical records of 98 patients (mean age, 55.6 +/- 8.59 years, 77.6 % males) who were consecutively discharged from hospital after undergoing a first liver transplant in our institution during 2012-2015. All visits to the emergency room during the first years after transplantation were analyzed, and survival at two years after transplantation was calculated. Fifty-six of the 98 patients (57.15 %) visited the emergency room on 117 occasions within the first year post-transplantation. Fever (n = 34; 29.05 %) and digestive symptoms (n = 32; 27.35 %) were the most common causes of consultation, and resulted in over half of visits. Thirty-five of these 56 patients (62.5 %) required an urgent readmission during 50 of the 117 (42.7 %) visits. This was primarily due to infectious complications (44 %) of diverse causes, (bacterial pneumonia, cholangitis, Clostridium difficile colitis) and biliary tract-related issues. The likelihood of readmission increased from 11.22 % at 30 days after discharge to 22.4 % at 90 days after discharge. Patient survival at 1 and 2 years after transplantation was lower for patients who were readmitted (88.4 % and 80.7 %, respectively) when compared to those who were not readmitted (95.56 % and 91.17 %, respectively, p = 0.002).Copyright © 2022 ARAN Ediciones S.A.. All rights reserved.

Avilés-Martínez María, A., et al. (2022). "[Benefits of a community physical exercise program prescribed from primary care for perimenopausal/menopausal women]." Atencion primaria 54(1): 102119.
	Objective: To measure the benefits of a physical exercise program in a community, through the modifications in quality of life, and perimenopausal-menopausal women physical condition.; Setting: The participants were recruited in PC consultations from two health centers in Molina de Segura (Murcia).; Participants: Women between 40 and 70 years old, or under 40 of age diagnosed with early menopause.; Design: Quasi-experimental study, non-randomized, controlled, open and single-center with 2 parallel branches to study.; Intervention: Experimental group: ACTIVA Bone Health Program for six months.; Control: inactive.; Main Measurements in Both Groups: The SF 36 questionnaire was used to measure the Quality of life.; Physical Condition: Aerobic condition, flexibility, balance and strength measured with the mile, flamenco, flexibility box tests, and throwing the medicine ball, respectively. Physical activity level through the GPPAQ Questionnaire. Sociodemographic variables were collected and the adherence to the program was measured.; Results: The quality of life improved in the intervention group compared to the control group, except «Body Pain» dimension (p = 0.412). As regards the intragroup level, all dimensions showed significant improvement except both «Physical Function» (p = 0.263) and «Body Pain» (p = 0.136). The physical capacities that benefited most were aerobic fitness, strength and balance.; Conclusions: The Active Bone Health Physical Exercise Program piloting showed benefits on participants' physical and mental quality of life. In addition, it has been shown that performing a specific physical exercise for premenopausal-menopausal women improves their physical condition. (Copyright © 2021 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aya, E., et al. (2021). "A comprehensive systematic review and network meta-analysis of anti-angiogenic agents in the treatment of ovarian cancer." PROSPERO International prospective register of systematic reviews.
	
Ayala, N., et al. (2024). Mindfulness, Optimism, and Resilience for Perinatal Health and Equity Study.
	No Results Available Behavioral: Digital Mindfulness Training Percentage of participants completing the assigned mindfulness exercises|Intervention acceptability|Dispositional optimism|Cesarean delivery|Hypertensive disorder of pregnancy|Gestational diabetes mellitus|Preterm birth|Traumatic birth|Postpartum post-traumatic stress symptoms Female Not Applicable 100 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 1983168 March 1, 2026

Aydin Cansu, M. and K. University (2023). Effect of Sage Essential Oil Inhalation Aromatherapy on Premenstrual Symptoms and Quality of Life.
	No Results Available Other: sage essential oil Personal Information Form:|Premenstrual Syndrome Scale (PMSS):|SF-36 Quality of Life Scale Female Not Applicable 86 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care KAFKAS-SAG-CMAYDIN-001 June 30, 2024

Ayele, T. M., et al. (2022). "Role of JAK2/STAT3 Signaling Pathway in the Tumorigenesis, Chemotherapy Resistance, and Treatment of Solid Tumors: A Systemic Review." Journal of Inflammation Research 15: 1349-1364.
	Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is a common signaling pathway used to transduce signals from the extracellular to the intracellular (nucleus) upon the binding of cytokines and growth factors to the extracellular domain of specific cell surface receptors. This signaling pathway is tightly regulated and has a multitude of biological functions such as cell proliferation, differentiation, and apoptosis. Besides, the regulated JAK2/STAT3 signaling plays a crucial role in embryonic development, hemopoiesis, and controlling the immune system. Conversely, aberrantly activated JAK2/STAT3 is frequently detected in varieties of tumors and involved in oncogenesis, angiogenesis, and metastasis of many cancer diseases that are usually refractory to the standard chemotherapy. However, the JAK3/STAT3 pathway recently emerged interestingly as a new site for the development of novel anti-tumor agents and becomes a promising therapeutic target in the treatment of many solid malignancies. Herein, this review aimed to provide insight into the JAK2/STAT3 pathway, in the hope to gain an understanding of its potential role in the pathogenesis, progression, chemotherapy resistance, and cancer therapy of solid tumors.Copyright © 2022 terms.php.

Aysu Yildiz, K., et al. (2023). "The Effect of Exercises Given to Menopausal Women on Symptom Severity and Sexuality: A Systematic Review and Meta-Analysis of Randomized Controlled Studies."
	
Azadi, A., et al. (2021). "Complications and objective outcomes of uterine preserving surgeries for the repair of pelvic organ prolapse versus procedures removing the Uterus, a systematic review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 267: 90-98.
	Background: Several authors have recently compared the outcomes and complications of surgical procedures that preserve or remove the uterus in the treatment of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Following the publication of several high quality randomized control trials on this topic we performed a new systematic review and meta analysis of this data.; Methods: We performed a systematic literature search in ClinicalTrials.gov, PubMed, Scopus, Ovid, EBSCO host, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled and cohort trials of uterine sparing prolapse repair (hysteropexy) versus hysterectomy with suspension. A total of 1285 patients from 14 studies were included in our systematic review and meta-analysis.; Results: Uterine sparing procedures (hysteropexy) were comparable to hysterectomy with suspension for recurrence rates (RR = 0.908, 95% CI [0.385, 2.143]), reoperation rates (RR = 1.517, 95% CI [0.802, 2.868]), length of hospital stay, (SMD = - 0.159 days, 95% CI [-0.375, 0.057]), voiding dysfunction (RR = 1.089, 95% CI [0.695, 1.706]), and intraoperative blood loss (SMD = - 0.339, 95% CI [-0.631, 0.047]). However, hysteropexy had shorter operative time than hysterectomy with suspension (SMD = - 1.191 h, 95% CI [-1.836, -0.545]), and fewer visceral injuries (RR = 0.421, 95% CI [0.244, 0.725]).; Conclusion: We found no significant differences in the outcomes or major complications of uterine preserving surgical procedures versus those which include hysterectomy in the treatment of POP. Hysteropexy procedures may be associated with a shorter operative time and fewer visceral injuries. This is consistent with older analyses.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Azadi, A., et al. (2023). "Vaginal Hysterectomy Compared With Laparoscopic Hysterectomy in Benign Gynecologic Conditions: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 142(6): 1373-1394.
	OBJECTIVE:To compare surgical efficacy outcomes and complications after laparoscopic hysterectomy and vaginal hysterectomy performed for benign gynecologic conditions.DATA SOURCES:We performed an online search in major databases, including PubMed, Scopus, Web of Science, ClinicalTrials.gov, and the Cochrane Library from 2000 until February 28, 2023.METHODS OF STUDY SELECTION:We searched for randomized controlled trials (RCTs) that compared vaginal hysterectomy with laparoscopic hysterectomy in benign gynecologic conditions. We located 3,249 articles. After reviewing titles and abstracts, we identified 32 articles that were eligible for full-text screening. We excluded nine articles as not-RCT or not comparing vaginal hysterectomy with laparoscopic hysterectomy. Twenty-three articles were included in the final systematic review, with 22 articles included in the meta-analysis.TABULATION, INTEGRATION, AND RESULTS:Twenty-three eligible RCTs included a total population of 2,408, with 1,105 in the vaginal hysterectomy group and 1,303 in the laparoscopic hysterectomy group. Blood loss and postoperative urinary tract infection rates were lower in the vaginal hysterectomy group than in the laparoscopic hysterectomy group (mean difference -68, 95% CI -104.29 to -31.7, P<.01, I2=95% and odds ratio 1.73, 95% CI 0.92-3.26, P=.03, I2=0%, respectively). Vaginal hysterectomy was associated with less total operative time, less recovery time, and greater postoperative pain on the day of surgery. Other complications, including conversion to laparotomy, visceral organ damage, or wound dehiscence, were uncommon. Because of insufficient data, we were not able to stratify by surgical indication. CONCLUSION(S):Vaginal hysterectomy had a shorter total operative time and recovery time but greater postoperative pain on day of surgery compared with laparoscopic hysterectomy.SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42023338538.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Azam, S., et al. (2020). "Hormone replacement therapy and mammographic density: a systematic literature review." Breast cancer research and treatment 182(3): 555-579.
	Purpose: Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic density (MD) is also a strong risk factor for breast cancer. We conducted this review to investigate the association between HRT use and MD and to assess the effect of different HRT regimens on MD.; Methods: Two of authors examined articles published between 2002 and 2019 from PubMed, Embase, and OVID using Covidence systematic review platform. Any disagreements were discussed until consensus was reached. The protocol used in this review was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality of each eligible study was assessed using the Oxford Center for Evidence-Based Medicine (OCEBM) hierarchy.; Results: Twenty-two studies met the inclusion criteria. Six studies showed that using estrogen plus progestin (E + P) HRT was associated with higher MD than estrogen alone. Four studies reported that continuous estrogen plus progestin (CEP) users had higher MD than sequential estrogen plus progestin (SEP) and estrogen alone users. However, two studies showed that SEP users had slightly higher MD than CEP users and estrogen alone users.; Conclusions: Epidemiological evidence is rather consistent suggesting that there is a positive association between HRT use and MD with the highest increase in MD among current users, and CEP users. Our results suggest that due to increase in MD and masking effect, current E + P users may require additional screening procedures, shorter screening intervals, or using advanced imaging techniques.

Azenkot, T. and B. Schwarz Eleanor (2022). "Special Considerations for Women of Reproductive Age on Anticoagulation." Journal of General Internal Medicine 37(11): 2803-2810.
	Anticoagulation poses unique challenges for women of reproductive age. Clinicians prescribing anticoagulants must counsel patients on issues ranging from menstruation and the possibility of developing a hemorrhagic ovarian cyst to teratogenic risks and safety with breastfeeding. Abnormal uterine bleeding affects up to 70% of young women who are treated with anticoagulation. As such, thoughtful clinical guidance is required to avoid having young women who are troubled by their menses, dose reduce, or prematurely discontinue their anticoagulation, leaving them at increased risk of recurrent thrombosis. Informed by a review of the medical literature, we present current recommendations for assisting patients requiring anticoagulation with menstrual management, prevention of hemorrhagic ovarian cysts, and avoiding unintended pregnancy. The subdermal implant may be considered a first-line option for those requiring anticoagulation, given its superior contraceptive effectiveness and ability to reliably reduce risk of hemorrhagic ovarian cysts. All progestin-only formulations-such as the subdermal implant, intrauterine device, injection, or pills-are generally preferred over combined hormonal pills, patch, or ring. Tranexamic acid, and in rare cases endometrial ablation, may also be useful in managing menorrhagia and dysmenorrhea. During pregnancy, enoxaparin remains the preferred anticoagulant and warfarin is contraindicated. Breastfeeding women may use warfarin, but direct oral anticoagulants are not recommended given their limited safety data. This practical guide for clinicians is designed to inform discussions of risks and benefits of anticoagulation therapy for women of reproductive age. (© 2022. The Author(s).)

Azienda Ospedaliero Universitaria, P. (2023). Laparoscopic Sacropexy and Vaginal Natural Orifice Transluminal Endoscopic Surgery Shull Suspension Comparison Trial.
	No Results Available Procedure: Laparoscopic cervicosacropexy|Procedure: Shull technique via V-NOTES operating time|post-operative pain|time to mobilization with standing|hospital stay|patient satisfaction|sexual function|recurrence of prolapse in apical compartment|recurrence of prolapse in the anterior and posterior compartments when present|postoperative complications|anesthesiological parameters Female Not Applicable 90 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment V-PULSE study December 2024

Azin, F. and H. Khazali (2022). "Phytotherapy of polycystic ovary syndrome: A review." International Journal of Reproductive Biomedicine 20(1): 13-20.
	BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex heterogeneous disease with various symptoms, which can affect females of reproductive age. Endocrine and metabolic abnormalities such as infertility, being overweight or obese, type 2 diabetes, hyperandrogenism and increased luteinizing hormone (LH) are common in women with PCOS. OBJECTIVE: This review aimed to assess the efficacy of non-chemical and herbal substances for PCOS recovery. MATERIALS AND METHODS: The keywords "non-chemical treatment", "herbal treatment", "polycystic ovary syndrome" and "PCOS" were used to search for articles in the electronic databases PubMed/MEDLINE, Web of Science, Scopus, and Reaxys, published from January 2009 to December 2019. RESULTS: 34 relevant studies were found and were briefly described in this review. The most effective herbal treatments in animal models of PCOS were used to restore abnormality in serum sex steroid profile, LH: follicle stimulating hormone ratio, steroidogenic enzymes, cardiovascular parameters, lipid profile, and glucose and estrous cycles. In PCOS patients, positive effects on PCOS due to reductions in testosterone, estrogen, LH, LH: follicle stimulating hormone ratio, and insulin levels were observed. CONCLUSION: The results of this reviewrevealed the variability and efficacy of phytotherapy and non-chemical treatments associated with PCOS disease. These findings may help future studies on the etiology and treatment of this syndrome.

Babbar, S., et al. (2021). "Meditation and Mindfulness in Pregnancy and Postpartum: A Review of the Evidence." Clinical Obstetrics and Gynecology 64(3): 661-682.
	Given their growing popularity, mindfulness practices including meditation are actively being studied in clinical trials to assess their efficacy at improving health outcomes during pregnancy and the postpartum period. We conducted a literature review to compile these studies and assessed their findings. There is sufficient evidence to support the practice of mindfulness practices in pregnancy to reduce anxiety, depression, and stress during pregnancy, which may continue to have beneficial effects through the postpartum period. There is limited evidence on the benefits of mindfulness and meditation for other aspects of pregnancy. However, due to the low-risk nature of these techniques, all women should be encouraged to engage in mindfulness practices during pregnancy.Copyright © 2021 Lippincott Williams and Wilkins. All rights reserved.

Babiker, H., et al. (2022). "Tilsotolimod Exploits the TLR9 Pathway to Promote Antigen Presentation and Type 1 IFN Signaling in Solid Tumors: A Multicenter International Phase I/II Trial (ILLUMINATE-101)." Clinical Cancer Research 28(23): 5079-5087.
	Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors. Patients and Methods: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the safety, establishing the dose, efficacy, and immunologic assessment. Blood samples and tumor biopsies of injected and noninjected lesions were obtained at baseline and 24 hours after treatment for immune analyses. Result(s): Thirty-eight and 16 patients were enrolled into the dose escalation and melanoma expansion cohorts, respectively. Deep visceral injections were conducted in 91% of patients. No dose-limiting toxicities (DLT) or grade 4 treatment-related adverse events were observed. Biopsies 24 hours after treatment demonstrated an increased IFN pathway signature and dendritic cell maturation. Immunologic profiling revealed upregulation of IFN-signaling genes and modulation of genes for checkpoint proteins. In the dose escalation cohort, 12 (34%) of 35 evaluable patients achieved a best overall response rate (ORR) of stable disease (SD), whereas 3 (19%) of 16 evaluable patients in the melanoma cohort achieved stable disease. Conclusion(s): Overall, tilsotolimod monotherapy was generally well tolerated and induced rapid, robust alterations in the tumor microenvironment.Copyright © 2022 American Association for Cancer Research.

Bacchi Ambrosano, G., et al. (2021). "Is the addition of vaginal electrical stimulation to transcutaneous tibial nerve electrical stimulation more effective for overactive bladder treatment? A randomized controlled trial." Actas Urologicas Espanolas 45(1): 64-72.
	INTRODUCTION AND OBJECTIVES: Overactive bladder (OAB) is a prevalent disorder that increases with age and impairs patients' quality of life. Guidelines recommend behavior modifications as the first-line treatment; however, physiotherapy has also been used with success, safety, and low cost. Transcutaneous tibial nerve electrical stimulation (TTNS) and vaginal electrical stimulation (VS) are being used in clinical physiotherapy practice. This study aimed to verify whether the addition of VS to TTNS is more beneficial than TTNS alone for women with OAB. PATIENTS AND METHODS: In all, 106 women aged >18 years diagnosed with OAB or mixed urinary incontinence with prevalent OAB symptoms were randomly divided into 2 groups: Group 1: TTNS (n = 52); Group 2: TTNS + VS (n = 54). The 3 day voiding diary, pelvic floor muscle strength (Ortiz Scale), King's Health Questionnaire, and Overactive Bladder Questionnaire were assessed before and after treatment. Urinary frequency was considered the primary outcome, and a reduction of ≥ 3 micturitions/day was considered clinically relevant. Mixed linear models were used to compare the 2groups. RESULTS: Initially, the groups were similar in age, body mass index, number of pregnancies, time of OAB onset, and prevalence of OAB symptoms. After treatment, a reduction in urinary frequency of 1.5 micturitions was observed in Group 2, which was not clinically relevant despite being statistically significant. CONCLUSIONS: The addition of VS to TTNS for the treatment of OAB was not more effective than TTNS as a single therapy.

Bachmann, C. (2023). "New Achievements from Molecular Biology and Treatment Options for Refractory/Relapsed Ovarian Cancer-A Systematic Review." Cancers 15(22).
	Ovarian cancer (OC) has a high rate of mortality and is the fifth most common cause of death in females all over the world. The etiology is still unclear. Numerous factors such as smoking, obesity, and unhealthy diet may affect the risk of OC. Having a family history of breast and OC is one of the main risks for developing OC. Mutations of BRCA1/2 are associated with OC risk as well. The histopathological classification of OC reveals the four most common types: serous, clear cell, endometrioid, and mucinous; these are epithelial OC types, and other types are rare. Furthermore, OC can be subdivided into types I and II. Type I tumors are most probably caused by atypical proliferative tumors. Type II tumors include high-grade carcinoma of the serous type, carcinosarcoma, and carcinoma, which are not differentiated and generally originate from tubal intraepithelial carcinoma of the serous type. Typically, type I tumors are present in early stages, usually with good prognosis. Type II tumors are classified as high-grade tumors and are most often diagnosed at advanced FIGO stages with poor prognosis. High-grade serous OC accounts for 90% of serous OC. Tumor heterogeneity aggravates OC treatment. The standard care for primary epithelial ovarian cancer (EOC) is cytoreductive surgery followed by platinum-based chemotherapy. Neoadjuvant chemotherapy can be used in certain cases followed by cytoreductive surgery. The main prognostic factor is complete tumor resection. However, about 70% of patients relapse. Resistance to chemotherapeutic agents remains a major challenge in EOC treatment, in which many different factors are involved. In recent years, the examination of molecular parameters and their prognostic impact has become increasingly relevant in EOC, and furthermore, the use of immunotherapy has expanded the therapeutic range. As the clinical need is greatest for relapsed patients, this systematic review will focus on recent advances in molecular biology with prognostic and predictive markers and treatment options for recurrent/refractory OC. Inclusion criteria for the review: potential prospective or predictive biomarkers in preclinical or clinical use in relapsed and refractory OC, prognostic impact, clinical and preclinical trials, and immunotherapy. Exclusion criteria for the review: primary OC, no full text or abstract available, not the topic mentioned above, and text not available in English. Risk of bias: the included studies were evaluated descriptively for the topics mentioned above, and data were not compared with each other. The objective is to highlight the molecular mechanisms of the most promising targeted agents under clinical investigation to demonstrate their potential relevance in recurrent/refractory OC.

Backes, F. J., et al. (2021). "Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal Cancer." Gynecologic Oncology 162(3): 619-625.
	OBJECTIVES: To estimate the maximally tolerated dose (MTD) and describe toxicities associated with lenvatinib and weekly paclitaxel in patients with recurrent endometrial and platinum resistant epithelial ovarian cancer. METHODS: Using a 3 + 3 design patients were given weekly paclitaxel 80 mg/m2 IV day 1, 8, 15 and oral levantinib daily on a 28-day cycle. Lenvatinib dose levels were 8 mg, 12 mg, 16 mg, 20 mg. Toxicities were recorded using CTCAE v4.03 and response was determined with imaging after cycle 2, then every 3rd cycle, using RECIST 1.1 criteria. RESULTS: 26 patients were enrolled; 19 with ovarian cancer (14 high grade serous, 1 low grade serous, 2 clear cell, 1 endometrioid, and 1 carcinosarcoma), and 7 with endometrial cancer (3 serous, and 4 endometrioid). The MTD was established at lenvatinib 16 mg and weekly paclitaxel 80 mg/m2. Toxicities (all grades) occurring in ≥25% of patients included anemia, neutropenia, lymphopenia, mucositis, nausea, diarrhea, anorexia, hypertension, fatigue, proteinuria, epistaxis, hoarseness. Twenty-three patients were evaluable for response and PFS; 15 (65%) had a partial response, 7 (30%) stable, 1 (4%) progressive disease with an objective response rate of 65%; 71% in ovarian and 50% in endometrial cancer. Median progression free survival (PFS) is 12.4 months; 14.0 months in endometrial cancer, 7.2 months in ovarian cancer; 54% had a PFS > 6 months. The median duration of response for PR patients (n = 15) was 10.9 months. CONCLUSIONS: The regimen was tolerable with manageable side effects. Encouraging activity was observed in endometrial and ovarian cancer, and warrants further development.

Bacorro, W., et al. (2022). "Outcomes with definitive radiotherapy among patients with locally advanced cervical cancer with relative or absolute contraindications to cisplatin: A systematic review and meta-analysis." Gynecologic Oncology 166(3): 614-630.
	Background: The standard treatment for locally advanced cervical cancer (LACC) is chemoradiation (CRT) with cisplatin, followed by brachytherapy, but is less defined for cisplatin-intolerant patients. We synthesized evidence on treatment outcomes with definitive radiotherapy (RT) with or without chemotherapy (ChT) in these patients.; Methods: We performed a systematic search and included 20 relevant studies. We extracted data on response, survival, compliance, and toxicity, and performed meta-analyses of outcome rates and risk ratios. Sensitivity and subgroup analyses were performed to explore sources of heterogeneity. Meta-regression was performed to examine the effects of other variables.; Results: Due to lack of comparative data, most comparisons were indirect and derived from the proportional meta-analyses. Complete response (85%) and survival (62% 5yOS) rates are comparable to those published for LACC without contraindications to cisplatin. Survival rate is better with CRT than RT alone (5yOS, 73% vs 58%), and with nodal boost (NB) than without (5yOS, 71% vs 56%). Carboplatin CRT is associated with lower 5yOS (44%) but better ChT compliance (86%) when compared to other interventions. ChT compliance is better in renal failure than elderly cohorts (89% vs 67%). RT compliance is lower with CRT than RT alone (90% vs 96%), and higher with NB than none (96% vs 93%). NB is associated with lower RT compliance than no NB, when ChT is given. Meta-regression results affirm ChT and NB to be significant positive factors for survival, and NB, which is associated with greater use of advanced RT techniques, for RT compliance.; Conclusion: For those with relative contraindications, cisplatin CRT is effective and well-tolerated. For those with absolute contraindications, carboplatin is well-tolerated but with unclear effectiveness. Nodal boost is effective and well-tolerated, but is less tolerated when concurrent ChT is given.; Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bączyk, G., et al. (2023). "Quality of Life for Polish Women with Ovarian Cancer during First-Line Chemotherapy." Healthcare (Basel, Switzerland) 11(18).
	Ovarian cancer is the worst prognostic gynaecological cancer and represents a grave clinical and social problem. Therefore, the study aimed to assess female patients' emotional, cognitive, physical, and social quality of life. The study included 100 patients diagnosed with ovarian cancer and treated with chemotherapy in a day hospital setting at the Department of Radiotherapy and Gynaecological Oncology at the Wielkopolska Oncology Centre in Poznań. The patients were given a standard treatment regimen: paclitaxel 175 mg/m 2 in a 3 h infusion and carboplatin at an AUC of 6 (5-7) following Calvert as a 1 h infusion for six cycles administered every 21 days. In addition, standardised questionnaires of the Polish version of the EORTC QLQ-C30 and QLQOV28 were used. The analysis of the collected material shows that the patients reported the highest level of general health and quality of life at the study's first stage, i.e., before chemotherapy (mean value of 59.67 points). In contrast, the patients' lowest level of general health and quality of life was observed in the fourth stage of the study (mean value of 45.04 points). The problem of side effects, such as nausea and vomiting, affected the entire study group and was more troublesome in the final stage of treatment for all patients. In the study's first stage, the mean score on the nausea and vomiting symptom scale was 16 points; in the fourth stage, the mean score was 40.07. Of the clinical factors, the symptom of fatigue was the most severe health problem for the subjects. The mean score of the fatigue scale in the study's first stage was 37.11 points, while a score of 70.33 was obtained in the fourth stage of the research. The multivariate linear regression model showed that the lack of professional activity lowers quality of life, especially combined with other side effects of chemotherapy, including hair loss in Stage IV of the study. This study shows that women with ovarian cancer undergoing chemotherapy need exceptional support from psychologists, nurses, dieticians, and physiotherapists.

Badawy, A., et al. (2023). "Retraction notice to "Extending clomiphene treatment in clomiphene-resistant women with PCOS: a randomized controlled trial" (RBMO 16/6 (2008) 825-829(10.1016/S1472-6483(10)60148-4))." Reproductive Biomedicine Online 47(5): 103374.
	This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editors. In response to several reports concerning the above paper, regarding the collection of data, the accuracy of analysis and data presentation, and conclusions presented in the article, RBMO editors investigated to verify the validity of the issues raised and determine the appropriate status of the paper. The investigation followed Elsevier's policy on publishing ethics, the flowcharts and guidelines provided by COPE, and the 'REAPPRAISED' checklist for the evaluation of publication integrity. The corresponding author, A. Badawy, and the institution where the trial took place responded to the editors' enquiries and are unable to provide the trial data required to resolve the concerns. The corresponding author advised that at the time the research was conducted, local policy required records to be destroyed after 5 years, thus, as the trial data are no longer available, post-publication concerns cannot be further investigated. Note at the time of submission, retention of raw data and data sharing was not a requirement. Additionally, an independent statistical review of the article found that the sample size was not appropriately calculated and not reproducible. Also, it was not discernible how the statistically significant treatment effect was obtained. Without the possibility of publishing a correction or explanation, the data presented in the paper remain unreliable, and therefore, in line with COPE recommendations, the journal editors agree that retraction is appropriate. The corresponding author, A. Badawy, does not agree with the retraction. The co-authors of the article, A. Allam and M. Abulatta, could not be contacted by the journal.Copyright © 2023

Badehnoosh, B., et al. (2024). "MiRNAs: Emerging Agents for Therapeutic Effects of Polyphenols on Ovarian Cancer." Mini reviews in medicinal chemistry 24(4): 440-452.
	In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo . Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Baekelandt, J., et al. (2021). "Adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery versus laparoscopy: results of a first randomised controlled trial (NOTABLE trial)." BJOG 128(11): 1782‐1791.
	Objective: To compare adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) versus laparoscopy. Design: Parallel group, 1:1 single‐centre single‐blinded randomised trial, designed as non‐inferiority study with a margin of 15%. Setting: Belgian teaching hospital. Population: Non‐pregnant non‐virgin women with an intact uterus and without obliteration of the pouch of Douglas scheduled to undergo removal of an adnexal mass assessed to be benign on ultrasound by IOTA criteria. Methods: Randomisation to laparoscopy (control group) or vNOTES (experimental group). Stratification according to adnexal size. Blinding of participants and outcome assessors by sham incisions. Main outcome measures: The primary outcome measure was adnexectomy by the allocated technique. Secondary outcomes included duration of surgery, pain scores and analgesics used, quality of life and adverse events. Results: We randomly assigned 67 participants (34 to the vNOTES group and 33 to the laparoscopy group). The primary end point was always reached in both groups: there were no conversions. We performed a sensitivity analysis for the primary outcome, assuming one conversion in the vNOTES group and no conversions in the laparoscopy group: the one‐sided 95% upper limit for the differences in proportions of conversion was estimated as 13%, which is below the predefined non‐inferiority margin of 15%. The secondary outcomes demonstrated a shorter duration of surgery, lower pain scores, lower total dose of analgesics and a trend for more adverse events in the vNOTES group. Conclusions: vNOTES is non‐inferior to laparoscopy for a successful adnexectomy without conversion. vNOTES allowed shorter operating times and less postoperative pain but there was a trend for more adverse events.

Baena-García, L., et al. (2022). "A 16-week multicomponent exercise training program improves menopause-related symptoms in middle-aged women. The FLAMENCO project randomized control trial." Menopause (New York, N.Y.) 29(5): 537-544.
	Objective: To investigate the influence of a supervised multicomponent exercise training program on menopause-related symptoms, particularly vasomotor symptoms (VMS), in middle-aged women.; Methods: A total of 112 middle-aged women (mean age 52 ± 4 y old, age range 45-60 y) from the FLAMENCO project (exercise [n = 59] and counseling [n = 53] groups) participated in this randomized controlled trial (perprotocol basis). The exercise group followed a multicomponent exercise program composed of 60-minute sessions 3 days per week for 16 weeks. The 15-item Cervantes Menopause and Health Subscale was used to assess the frequency of menopause-related symptoms.; Results: After adjusting for body mass index and Mediterranean diet adherence, the subscales measuring menopause-related symptoms and VMSs decreased 4.6 more in the exercise group compared to the counseling group (between-group differences [B]: 95% CI: -8.8 to -0.2; P = 0.040). The exercise group also showed significant improvements in the subscales of couple relationships (between-group differences [B]: -1.87: 95% CI: -3.29 to - 0.45; P = 0.010), psychological state (between-group differences [B]: -2.3: 95% CI: -5 to -0.2; P = 0.035), and VMSs (between-group differences [B]: -4.5: 95% CI: -8.8 to -0.2; p = 0.040) in the Cervantes Menopause and Health Subscale compared with the counseling group.; Conclusions: A 16-week multicomponent physical exercise program showed a positive effect on menopause- related symptoms especially in couple relationships, psychological state, and VMS, among 45 to 60 year old women.; Competing Interests: Financial disclosures/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Bagkou, D., et al. (2022). "Understanding human immunity in idiopathic recurrent pregnancy loss." European Journal of Obstetrics, Gynecology, and Reproductive Biology 270: 17-29.
	Miscarriage, defined as the loss of a pregnancy before a viable gestation, affects 1 in 6 couples. Recurrent pregnancy loss (RPL), defined as two or more miscarriages, affects up to 1.9% of couples. The physical, psychological, and financial impact of miscarriage can be substantial. However, despite its multifactorial etiology, for up to 50% of couples a reason behind this condition cannot be identified, termed 'idiopathic RPL'. Much recent research has strived to understand this, with immune dysregulation being a source of particular interest. In this short review we summarize the current evidence on the complex role of the immune system both pre- and early post-conception in RPL. A key question is whether systemic peripheral blood markers, in particular natural killer cell and T cells, may be utilized to accurately predict and/ or diagnose those pregnancies at high risk of loss. Given the invasive nature of endometrial testing, identification of reliable peripheral immune biomarkers is particularly appealing. Clinical trials using potent immunomodulatory agents, including intravenous immunoglobulin, donor leukocyte immunization, and tumor necrosis factor (TNF)-α inhibitors, have been undertaken with the primary objective of preventing miscarriage in women with RPL. Standardisation of both diagnostic and prognostic immune cell testing assays is required to permit accurate identification of those women who may benefit from immunomodulation. Prompt clarification is required to meet the increasing expectation from couples and clinicians, as without these advancements women are at risk of exposure to potent immune-therapies and subsequent studies are at risk of failure, generating further controversy regarding the role of immune dysregulation in women with RPL. Through this review we highlight clear gaps in our current knowledge on immune activity in RPL. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Baglini, E., et al. (2023). "Tyrosine kinase inhibitors (TKIs) for ovarian cancer treatment: from organic to inorganic chemotherapeutics towards selectivity-a perspective overview." Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine.
	Ovarian cancer (OC) is a lethal gynecologic cancer in industrialized countries. Treatments for OC include the surgical removal and chemotherapy. In the last decades, improvements have been made in the surgery technologies, drug combinations and administration protocols, and in diagnosis. However, mortality from OC is still high owing to recurrences and insurgence of drug resistance. Accordingly, it is urgent the development of novel agents capable to effectively target OC. In this respect, tyrosine kinase inhibitors (TKIs) may play an important role. Most of TKIs developed and tested so far are organic. However, owing to their chemical versatility, also metals can be exploited to design selective and potent TKIs. We provide a short and easy-to-read overview on the main organic TKIs with a summary of those that entered clinical trials. Additionally, we describe the potential of metal-based TKIs, focusing on this overlooked family of compounds that may significantly contribute towards the concept of precision-medicine. (© 2023. The Author(s).)

Bagrat, G., et al. (2021). "Pentosan polysulfate in patients with bladder pain syndrome/interstitial cystitis: systematic review and meta-analysis."
	
Bahena, J. A., et al. (2021). "Retrospective analysis of the impact of bevacizumab dose-intensity on the survival of platinum-resistant ovarian cancer patients." Annals of Oncology 32(Supplement 5): S750-S751.
	Background: Bevacizumab (BVZ) is a humanized monoclonal antibody that has demonstrated benefit in the front-line, recurrent platinum-sensitive and recurrent platinum-resistant ovarian cancer settings. Phase III trials of BVZ in ovarian cancer show a benefit in the dose-intensity range of 2.5 mg/kg/week to 5 mg/kg/week, but the optimal dose of this drug is still unknown. Some evidence suggests that high-dose BVZ is associated with a higher incidence of adverse events. In addition, in many countries, health services have restricted access to BVZ due its high cost. Method(s): We carried out a retrospective study comparing low-dose (< 2.5 mg/kg/week) and high-dose (> 2.5 mg/kg/week) BVZ in combination with chemotherapy, in patients with recurrent platinum-resistant ovarian cancer that received treatment in the Instituto Nacional de Cancerologia between 2012 and 2017. Demographic and clinicopathological characteristics were retrieved from medical records. We compared PFS and OS by use of a log-rank test. We also examined BVZ adverse events of special interest. Result(s): Of 79 patients that received BVZ, 41 received low dose and 38 received high dose. Mean dose was 2.3 mg/kg/week in the low-dose group and 4.22 mg/kg/week in the high-dose group. No differences in mean age, history of hypertension and number of BVZ cycles were found between groups. The low-dose group had a higher proportion of low-grade serous histology (9.8% vs 0%), and a lower proportion of clear-cell histology (4.9% vs 10.5%). Median PFS was 7.5 months (CI 95%, 0.56 - 1.7) with low dose and 7.7 months (CI 95%, 0.58 - 1.7) with high dose (p = 0.81). OS was 28.1 months (CI 95%, 0.68 - 2.4) and 21.6 months (CI 95%, 0.40 - 1.4) (p = 0.09). There were no differences in the incidence of adverse events of special interest. Conclusion(s): Results from this retrospective study suggest that low-dose BVZ may have a similar efficacy compared to high-dose. The administered dose did not affect the incidence of BVZ-related adverse events. However, clinical data from prospective studies need to be assessed in order to validate these results. If low-dose BVZ treatment demonstrates to be non-inferior, a larger number of patients will be able to receive this treatment with a better cost-effectiveness ratio. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2021 European Society for Medical Oncology

Bahmani, M., et al. (2022). "The effect of pomegranate seed oil on human health, especially epidemiology of polycystic ovary syndrome; a systematic review." JBRA Assisted Reproduction 26(4): 631-636.
	Polycystic ovary syndrome is the most common endocrine disorder in women. Today, medicinal plants have been considered by women, especially in the reproductive and pregnancy ages. Multiple drug treatments and the length of the treatment period often lead to incomplete treatment by patients. Therefore, due to the side effects of chemical drugs, this study was conducted to assess investigate the effect of pomegranate seed oil on polycystic ovary syndrome. The prevalence of polycystic ovary syndrome is increasing by 15 to 20% and clinically includes oligomenorrhea or amenorrhea, hirsutism, and often infertility. Databases such as Cochran library, Medline, PubMed, SID, and Science Direct were used to access the related articles. To collect the required information, first, the articles that had one of the keywords of medicinal plants, polycystic ovary syndrome, plant, pomegranate extract, and menstrual irregularities in their text were searched in databases. All studies from 1985 to 2021 are included in the study. Conjugated linolenic acid (CLN) is a group of geometric and positional isomers of linolenic acid in which double bonds are conjugated. CLN has been reported to have a very strong cytotoxic effect on tissue tumor cells in the body, preventing cancer, reducing the accumulation of triacylglycerol in the liver, polycystic ovary syndrome, and LDL cholesterol in the blood. So far, seven CLN isomers have been identified, including ponic acid in pomegranate seed oil. Conjugated linoleic acid (CLA) is a group of situational and geometric isomers of linoleic acid in which double bonds are conjugated. The positive effects of the two main CLA isomers (cis-9, trans-11, and trans-10, cis-12) include inhibiting the growth of cancer, reducing the risk of atherosclerosis, and reducing body fat.

Bahrami, F., et al. (2023). "Complications following surgeries for endometriosis: A systematic review protocol." PloS One 18(5): e0285929.
	Background: Endometriosis is a common gynecological condition with a wide range of symptoms, including infertility, dyspareunia, intestinal disorders, and pelvic pain. Laparoscopy and laparotomy are used widely for diagnosing and managing endometriosis. We will conduct a systematic review and meta-analysis with the aims of reporting complications rates following each type of surgeries for endometriosis and determinants of complications.; Method: We will search Medline (via PubMed), Embase, the Cochrane Library, Web of Science, and Google Scholar for both retrospective and prospective cohorts or trials of at least 30 participants reporting perioperative and postoperative complications for endometriosis surgeries. We will restrict the studies to those conducted after 2011, to be representative of current practices, and will exclude studies of surgeries for gynecological cancer, or other concomitant benign gynecologic surgeries such as myomectomy. Two reviewers will independently screen references and select eligible studies. A standardized form will be used to collect data related to the baseline characteristics, potential determinants of complications, types of interventions, and outcomes. Cumulative incidences of complications will be pooled using DerSimonian and Laird random-effects method. The relation between potential determinants and complications will be reported with risk ratios and their 95% of confidence intervals. Subgroup analysis of surgical approach, surgical procedure, superficial and deep infiltrating endometriosis, and the indication of surgery will be conducted. Sensitivity analyses restricted to studies with low risk of bias will be performed.; Discussion: This systematic review will provide information on the rates of complications for different surgical approaches and procedures for the treatment of endometriosis. It will contribute to inform patients when making decisions regarding their care. Identifying potential determinants of complications will also help to improve care by identifying women being at higher risk of complications.; Trial Registration: Systematic review registration: CRD42021293865.; Competing Interests: The authors have no conflict of interest to declare. (Copyright: © 2023 Bahrami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bahroudi, Z., et al. (2022). "Review of ovarian tissue cryopreservation techniques for fertility preservation." Journal of Gynecology Obstetrics and Human Reproduction 51(2): 102290.
	Ovarian failure and ovarian malfunction are among major fertility problems in women of reproductive age (18-35 years). It is known that various diseases, such as ovarian cancer and premature ovarian failure, besides certain treatments, such as radiotherapy and chemotherapy of other organs, can affect the normal process of folliculogenesis and cause infertility. In recent years, various procedures have been proposed for the treatment of infertility. One of the newest methods is the use of cryopreservation ovarian fragments after cancer treatment. According to some studies, this method yields very satisfactory results. Although ovarian tissue cryopreservation (OTC) is an accepted technique of fertility preservation, the relative efficacy of cryopreservation protocols remains controversial. Considering the controversies about these methods and their results, in this study, we aimed to compare different techniques of ovarian cryopreservation and investigate their advantages and disadvantages. Reviewing the published articles may be possible to identify appropriate strategies and improve infertility treatment in these patients.Copyright © 2021 Elsevier Masson SAS

bai, w. and S. Fenfang (2023). "The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis."
	
Bai, Y.-Y., et al. (2019). "Clinicopathological and prognostic significance of pretreatment thrombocytosis in patients with endometrial cancer: a meta-analysis." Cancer Management and Research 11: 4283-4295.
	Background: The prognostic and clinicopathological role of pretreatment thrombocytosis in cancer has been widely studied, but conclusions in endometrial cancer (EnCa) remain controversial. Therefore, we conducted a meta-analysis to assess the pathologic and prognostic impacts of pretreatment thrombocytosis in patients with EnCa. Methods: We searched PubMed, Embase, SpringerLink, ScienceDirect and China National Knowledge Infrastructure databases. Pooled HR or OR with their 95% CIs were applied to assess the association of pretreatment thrombocytosis with survival outcomes and clinical parameters of EnCa patients. Results: In total, 10 studies containing 2,995 cases of EnCa met the criteria. The results suggested that pretreatment thrombocytosis was significantly associated with high International Federation of Gynecology and Obstetrics (FIGO) stage (pooled OR 3.45, 95% CI 1.68-7.08, P =0.001), poor tumor differentiation (pooled OR 2.00, 95% CI 1.22-3.29, P =0.006), lymph-vascular space invasion (pooled OR 2.04, 95% CI 1.35-3.07, P =0.001); myometrial invasion (pooled OR 2.14, 95% CI 1.39-3.32, P =0.001); cervical involvement (pooled OR 2.54, 95% CI 1.56-4.15, P =0.000) and lymph node metastasis (OR 3.15, 95% CI 1.71-5.80, P =0.001). No significant difference existed between pretreatment thrombocytosis and overall survival ( P =0.012), cancer/disease-specific survival ( P =0.07) or disease-free survival ( P =0.25). Conclusion: pretreatment thrombocytosis was associated with advanced clinicopathological features in patients with EnCa, which may serve as a potential therapeutic target for EnCa.; Competing Interests: The authors report no conflicts of interest in this work.

Bai, Z., et al. (2024). "Prevalence and Risk Factors of Urinary Retention in Patients With Cervical Cancer: A Meta-analysis and Systematic Review." Cancer Nursing.
	Background: The literature is inconsistent on the prevalence and risk factors of urinary retention in patients with cervical cancer.; Objective: The aim of this study was to review the literature on the prevalence of urinary retention in patients with cervical cancer and consolidate the risk factors.; Methods: For this meta-analysis, eligible articles published in English or Chinese by December 10, 2021, were systematically searched for and retrieved from PubMed, Cochrane Library, Ovid-Embase Medline, Web of Science, PsycINFO, CINAHL, and Scopus. Prevalence, odds ratios (ORs), and 95% confidence intervals (CIs) were used for meta-analysis.; Results: Twenty-five studies were included in the analysis. The pooled overall prevalence was 0.26 (95% CI, 0.21-0.30, I2 = 95.0%). The identified risk factors were age (OR, 1.13; 95% CI, 1.08-1.19), urinary tract infection (UTI) (OR, 3.33; 95% CI, 1.48-7.49), surgical extent (OR, 2.95; 95% CI, 1.27-6.85), and catheter indwelling time (OR, 3.44; 95% CI, 2.43-3.87).; Conclusions: The prevalence of urinary retention in patients with cervical cancer is 0.26. Older age, UTI, longer catheter indwelling time, and a larger surgical extent may increase the risk of urinary retention. Clinicians should identify patients at risk and adopt interventions such as individualized catheter care.; Implications for Practice: Nursing staff should assess the risk of urinary retention in a patient with cervical cancer according to her age, presence of UTI, surgical extent, and catheterization time. A carefully chosen surgical procedure and interventions such as individualized education, timely catheter removal, treatment of UTI, and rehabilitation should be offered.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Baillargeon, J. P., et al. (2022). "An interdisciplinary intervention improves lifestyle behaviours in women living with obesity and infertility: a randomized controlled trial." Journal of the Endocrine Society 6(Supplement 1): A674-A675.
	Introduction: Lifestyle modifications should be the firstline treatment for improving reproductive function and preconception weight in women living with obesity who are seeking fertility treatments. Evidence is however scarce regarding the effectiveness of lifestyle programs in supporting these women. The study's objective was therefore to determine whether the Obesity-Fertility program leads to healthier lifestyle behaviours in women living with obesity and consulting at a fertility clinic. Method(s): Women with obesity and infertility were randomized to the control (CG=65) or intervention (IG=65) group. Based on the participant's medical record, randomization was stratified according to the polycystic ovarian syndrome status. The CG followed the usual fertility clinic approach while the IG participated in individual and group sessions with a registered dietician, a kinesiologist, and a psychologist. Before the intervention (baseline) and 6 months after (V6), frequency of food and beverages intakes, physical activity levels, sedentary time, daily sleep duration, alcohol consumption and smoking use were collected via a lifestyle behaviour questionnaire adapted from the 2009 Canadian Community Health Survey (Statistics Canada). Functional capacity was evaluated with a 6-minute walk test. Descriptive statistics, two-sample tests of means or proportions, generalized linear models and logistic regressions were performed. Result(s): At baseline, women who had a research visit at 6+/-1 months (n=85) were 30+/-5 years old and had a BMI of 39.8+/-7.7 kg/m2. Most of them held no university degree (81.2%) and were primiparous (56.5%). Both groups (CG=43 and IG=42) had similar sociodemographic and anthropometric characteristics as well as lifestyle behaviours at baseline except for smokers' proportion that was higher in CG (CG: 34.9% vs IG: 9.5%, p<0. 01). From baseline to 6 months, whole fruit and vegetable frequency intakes increased more in the IG vs CG (fruits: +1.1 vs +0.4/day, p<0. 01; vegetables: +0.7 vs +0.4/day, p<0. 01). Significant differences (IG vs CG) were also observed for frequency intakes of whole grain products (+1. 0 vs +0. 04/day, p<0. 01) and dairy products (+0.5 vs -0.2/day, p<0. 01) as well as in the percentage of active women (>3 kcal/kg/day: +14.2% vs +2.3%, p=0. 03) and the time spent in sedentary behaviours (-6.7 vs -0.1 h/ week, p<0. 01). Distance covered during the 6-minute walk test tended to increase more in IG vs CG (+28.8 vs +5.5 metres, p=0. 05). Sleep duration decreased by 19 and 12 minutes per day in the IG and CG, respectively (p=0.25). No significant difference was found between IG and CG for changes in sleep duration, alcohol consumption and smoking use. Conclusion(s): The Obesity-Fertility program significantly improved components of diet, physical activity levels and sedentary behaviours in women living with obesity and seeking fertility treatments. Such programs can therefore support these women to adopt healthier lifestyle behaviours and may improve their fertility as well as decrease risks of complications during pregnancy.

Bais, A. and P. Phansopkar (2021). "Impact of pilates training versus progressive muscle relaxation technique on quality of life in menopausal women-a comparative study." Indian journal of forensic medicine and toxicology 15(1): 7‐11.
	Background: Menopausal women shows common symptoms which includes night sweats and hot flushes, heart distress, disturbances in sleep, depression, irritability, anxiousness, weight changes, physical and mental fatigue, joint and muscle pain. This affects the Quality Of Life of the Menopausal women. Pilates Training has proven beneficial for enhancing Quality Of Life in menopausal women but there is paucity of evidence of effect of Progressive Muscle Relaxation Technique in Menopausal women on QOL. The research is an initiative study that focuses on the effectiveness of PMRT on the various aspects of Quality Of Life of the menopausal women and comparison of the Pilates training and PMRT in order to enhance the QOL of participants. Aim and Objective: Effect of Pilates training & Progressive Muscle Relaxation Technique on menopausal women’s Quality Of Life and comparison of both the technique. Methods: 42 participants aged more than 45 years will be randomly categorized in two groups: Group A (n= 21) and Group B (n=21). The study duration will be of 6 months. The pre and post Intervention will be taken from both the group and data will be analyzed with the help of main outcome measure which is Menopause specific Quality Of Life (MENQOL). Result‐The expected result would include the details about whether the measures are effective for improving the quality of life in menopausal women, as well as the comparison of both the interventions. Data will be analyzed using paired t‐test. Conclusion‐It will be published after results are analyzed.

Bajalan, Z., et al. (2019). "Nutrition as a Potential Factor of Primary Dysmenorrhea: A Systematic Review of Observational Studies." Gynecologic and Obstetric Investigation 84(3): 209-224.
	Background: The incidence and severity of primary dysmenorrhea are influenced by various factors. The aim of the present study was to review nutritional factors influencing primary dysmenorrhea.; Methods: Academic databases including Web of Science, EMBASE, Scopus, and PubMed (including Medline) were searched using keywords of nutrition, diet, and primary dysmenorrhea. In this study, observational studies that were published in English from 1990 to April 2018, which focused on nutritional factors affecting primary dysmenorrhea, were selected. The evaluation of studies was performed using a modified STROBE checklist with 10 items.; Results: Out of 5,814 retrieved studies, 38 articles met inclusion criteria and were included for final data synthesis. The increased consumption of fruits and vegetables as the sources of vitamins and minerals, as well as fish and milk and dairy products have positive associations with less menstrual pain. Inconsistent results were reported on the consumption of other nutritional groups. Studies showed negative associations of meal skipping and following diet to lose weight with severity of dysmenorrhea.; Conclusion: A few studies showed inconclusive findings due to methodological heterogeneities for assessing nutritional habits and different methods of measuring dysmenorrhea pain. Therefore, further analysis and future interventional studies with stronger methodologies are required. (© 2019 S. Karger AG, Basel.)

Bak Malene, E., et al. (2023). "Clinical experiences with online adaptive radiotherapy of vulvar carcinoma." Acta oncologica (Stockholm, Sweden) 62(10): 1230-1238.
	Background and Purpose: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy.; Materials and Methods: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions).; Results: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively.; Conclusion: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Bakan, A. B., et al. (2021). "Effects of the Training Given to Older Adults on Urinary Incontinence." Ageing international 46(3): 324‐336.
	
Bakay, K., et al. (2021). "Hypogastric artery ligation in laparoscopic hysterectomy: results from a randomized controlled trial." Clinical and experimental obstetrics & gynecology 48(6): 1304‐1310.
	Background: Concerning total laparoscopic hysterectomy (TLH), opening the retroperitoneum and prophylactic ligation of both uterine arteries (UA) is not a routine procedure during a simple hysterectomy and it is not practiced widely in gynecology education. Methods: In this study, we tried to show the prophylactic ligation of internal iliac artery anterior division (IIAD) and provide hemostasis of UA at an anatomical plane where we considered it would be easier to perform and relatively safer, in terms of distance, regarding ureteric injury, in a prospective randomized controlled trial. Results: When this technique was used the duration of the operation got longer approximately 3 minutes (min) (57.15 ± 5.46 vs. 53.66 ± 8.96 p = 0.018 and p < 0.05), but the amount of bleeding was detected to be at a significantly lower level (73.84 ± 7.18 vs. 113.96 ± 21.5 p = 0.001 and p < 0.05). Discussion: In this method, not only we found out that it is easier to ligate IIAD compared to other surgical techniques but also allows for better control of the retroperitoneal area during the procedure therefore minimizing the risk of surgical complications such as ureter damage. Moreover, as was hypothesized, IIAD ligation dramatically reduced blood loss hence verifying its use in more complex hysterectomies and pelvic lymphadenectomy.

Bakhbakhi, D., et al. (2023). "Interventions, outcomes and outcome measurement instruments in stillbirth care research: A systematic review to inform the development of a core outcome set." BJOG: An International Journal of Obstetrics and Gynaecology 130(6): 560-576.
	Background: A core outcome set could address inconsistent outcome reporting and improve evidence for stillbirth care research, which have been identified as an important research priority. Objective(s): To identify outcomes and outcome measurement instruments reported by studies evaluating interventions after the diagnosis of a stillbirth. Search strategy: Amed, BNI, CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycINFO, and WHO ICTRP from 1998 to August 2021. Selection Criteria: Randomised and non-randomised comparative or non-comparative studies reporting a stillbirth care intervention. Data Collection and Analysis: Interventions, outcomes reported, definitions and outcome measurement tools were extracted. Main Result(s): Forty randomised and 200 non-randomised studies were included. Fifty-eight different interventions were reported, labour and birth care (52 studies), hospital bereavement care (28 studies), clinical investigations (116 studies), care in a multiple pregnancy (2 studies), psychosocial support (28 studies) and care in a subsequent pregnancy (14 studies). A total of 391 unique outcomes were reported and organised into 14 outcome domains: labour and birth; postpartum; delivery of care; investigations; multiple pregnancy; mental health; emotional functioning; grief and bereavement; social functioning; relationship; whole person; subsequent pregnancy; subsequent children and siblings and economic. A total of 242 outcome measurement instruments were used, with 0-22 tools per outcome. Conclusion(s): Heterogeneity in outcome reporting, outcome definition and measurement tools in care after stillbirth exists. Considerable research gaps on specific intervention types in stillbirth care were identified. A core outcome set is needed to standardise outcome collection and reporting for stillbirth care research.Copyright © 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.

Bakker, A., et al. (2022). "Comparison of the clinical performance of a hybrid Alba 4D and the AMC-4 locoregional hyperthermia systems." International Journal of Hyperthermia 39(1): 1408-1414.
	Objective: The in-house developed 70 MHz AMC-4 locoregional hyperthermia system has been in clinical use since 1984. This device was recently commercialized as the Alba 4D (Medlogix, Rome, Italy), with a similar geometrical 4-waveguide design. At the time of this study a hybrid Alba 4D was installed at our center, which incorporated elements of the AMC-4. This study aims to compare clinical performance of both devices. Method(s): During one year after clinical acceptance of the hybrid Alba 4D, both devices were used for treatment delivery in patients scheduled for locoregional hyperthermia. Each patient started with the AMC-4, next sessions were allocated to either device. Possible differences between Alba 4D and AMC-4 sessions in power, achieved temperature T0, T10, T50, T90, T100, treatment time and complaints per session, were evaluated using linear mixed models (LMMs) for repeated measures with patient as random effect. Result(s): From March 2018 to April 2019, eleven patients with cervical, pancreatic, vaginal carcinoma and uterine leiomyosarcoma received 27 locoregional hyperthermia sessions with the Alba 4D and 34 sessions with the AMC-4. Median number of sessions per patient was 5 (range 3-13). Treatment results for both devices were not significantly different: T50 was 40.5 +/- 1.0 degreeC vs. 40.8 +/- 0.7 degreeC, applied power was 500 +/- 79 W vs. 526 +/- 108 W, for the Alba 4D vs. AMC-4, respectively. Conclusion(s): Results of the first patients treated with the hybrid Alba 4D demonstrated comparable clinical performance of the Alba 4D and AMC-4 locoregional hyperthermia systems, and both devices are expected to yield similar favorable clinical results.Copyright © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Bakun Oksana, V., et al. (2023). "A NEW APPROACH TO ASSISTED REPRODUCTIVE TECHNOLOGIES PREPARATION IN WOMEN WITH ENDOMETRIOSIS ASSOCIATED INFERTILITY USING PROBIOTICS." Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 51(3): 234-238.
	Objective: Aim: To examine the expression Nlrp3-inflammasome in the blood of women with endometriosis-associated infertility using assisted reproductive technologies with included probiotic and estimate a new approach with included probiotic for preparation to assisted reproductive technologies.; Patients and Methods: Materials and methods: For the purpose of the research we examined 30 infertile women. Control group consisted of 10 women with tubal infertility due to an inflammatory process in the anamnesis, in whom, as a result of a complex clinical and laboratory examination, no other diseases were detected and in terms of their health they could be equated with practically healthy women (age from 21 to 42 years, the average age was 29.75 years) and who did not take probiotic. The main group consists from 20 women with external genital endometriosis were included in assisted reproductive technologies. Patients from main group took probiotic produced by Unic Biotech Ltd, India. 1 tablet twice a day with 10×109 Lactobacillus during 1 month in complex preparation (treatment) before assisted reproductive technologies. The indices of Nlrp3 - Inflammasome determined before and after preparation. The study was performer in Bukovinian State Medical University and Centre of Reproductive Medicine. To analyze the expression of the NLPP3-inflammasome gene and determine the relative normalized expression of NLPP3 mRNA, we used the polymerase chain reaction with reverse transcription in real time (RT-PCR). The object for molecular genetic studies by the RT-PCR method was the fraction of mononuclear cells isolated from the whole blood of patients with endometriosis. The value of p (authenticity difference) was determined by Student's table-Fischer. Differences between contrasting averages were considered significant at p <0.05.; Results: Results: Analized the results of our research stated that in main group expression of Nlrp-3 inflammasome was 24,43, which is significantly higher than after preparation (0,70 accordingly). In control group expression of Nlrp3-inflammasome was 0,54. Expression of Nlrp-3 inflammasome increased in patients before preparation more than 34 times compare with patients after preparation accordingly.; Conclusion: Conclusions: consequently, after using probiotic, the increased level of Nlrp3-inflammasome sharply decreases, indicating the effectiveness and the possibility of use in the programme for assisted reproductive technologies preparation.

Bal, Z. and T. Uçar (2023). "The effect of cognitive behavioural therapy and eye movement desensitization and reprocessing techniques on infertile women: a randomized controlled trial." Reproductive Biomedicine Online 48(2): 103612.
	RESEARCH QUESTION: What effects do training programmes based on cognitive behavioural therapy (CBT) and eye movement desensitization and reprocessing (EMDR) techniques applied to infertile women affected psychologically and emotionally by infertility have on post-traumatic stress disorder (PTSD) and psychological development? DESIGN: This randomized controlled study was conducted between May 2021 and August 2022. The study population included 90 infertile women referred to the IVF unit of a hospital in a province in eastern Turkey: 30 in the CBT group, 30 in the EMDR group and 30 in the control group. Data were collected using a personal information form, the Subjective Units of Disturbance Scale (SUDS), the Validity of Cognition (VoC) scale, the Infertility Distress Scale (IDS), the Impact of Event Scale-Revised (IES-R) and the Post-traumatic Growth Inventory (PTGI). Women in the experimental groups (CBT and EMDR groups) received the intervention in six sessions over 3 weeks. Pre-tests were administered to both experimental groups and the control group, and post-tests were conducted 3 weeks after the intervention. RESULTS: The mean scores on the SUDS, IDS and IES-R for women in the experimental groups were significantly lower compared with those for women in the control group following the interventions (P < 0.001). The mean scores on the VoC scale and PTGI for women in the experimental groups were significantly higher compared with those for women in the control group following the interventions (P < 0.001). CONCLUSION: The use of CBT and EMDR techniques reduced the negative psychological and emotional effects of infertility among infertile women.

Bala, R., et al. (2024). "Revitalizing allicin for cancer therapy: advances in formulation strategies to enhance bioavailability, stability, and clinical efficacy." Naunyn-Schmiedeberg's archives of pharmacology 397(2): 703-724.
	The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Balakrishnan, P. S. and A. Thomas (2022). "Stress Urinary Incontinence among Young Nulliparous Females-A Systematic Review." Journal of Pharmaceutical Negative Results 13: 1384-1389.
	Unintentional urination, also known as urinary incontinence (UI), is most frequently observed in postpartum and postmenopausal women. There is an association between UI and high-impact physical activity. Levator ani muscle (LAM) typically aids in urethral closure. However, in young female athletes, it indirectly places pressure on the lower tier of pelvic support by raising intraabdominal pressure and experience stress incontinence. The first line of treatment for young nulliparous females is pelvic floor muscle training(PFM).The objective of this study is to identify potential risk factors and explore the relationship between stress urinary incontinence(SUI) and athletic sports and dancers in young nulliparous females. Due to ignorance and underreporting, SUI frequently goes undiagnosed and unreported. Literature was retrieved through searching 5 electronic data-bases (PubMed, MEDLINE, CINAHL, Cochrane, and Google Scholar). Articles published from the year 2012 up to including 2022 with full text were included. 6 studies were included in this systematic review. Results indicated that SUI can be managed with few preventive techniques and PFM training. Thus it can be concluded its prevalence and exercises in reduction of SUI in nulliparous female athletes and dancers.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Balasubramanian, R., et al. (2023). "A Review of Clinical and Preclinical Studies on the Therapeutic Potential of Black Seeds (Nigella sativa) in the Management of Polycystic Ovarian Syndrome (PCOS)." Journal of Pharmacopuncture 26(1): 1-9.
	Objectives: Polycystic ovary syndrome (PCOS) is a condition that occurs frequently among women of reproductive age and is a polygenic, multifactorial, endocrine, and metabolic disorder. PCOS is becoming more common as a result of risk factors such as current lifestyle, overnutrition, and stress. The use of traditional herbal medicine is higher among the global population. Hence, this review article focuses on the potential of Nigella sativa to manage women with PCOS. Method(s): A literature search was carried out using databases including Medline, Google Scholar, EBSCO, Embase, and Science Direct, as well as reference lists, to identify relevant publications that support the use of N. sativa in the management of women with PCOS. Result(s): Several clinical and preclinical studies have demonstrated that the major bioactive constituent of black seed (N. sativa), thymoquinone, has potential for managing women with PCOS. Moreover, N. sativa may help to manage oligomenorrhea and amenorrhea in women with PCOS through its anti-inflammatory and antioxidant properties. Conclusion(s): N. sativa has potential for use as a herbal medicine for managing women with PCOS as an integrative medicine along with traditional and modern medicine in conjunction with calorie restriction and regular exercise.Copyright © Korean Pharmacopuncture Institute.

Balazs, H., et al. (2022). "The effect of topical imiquimod treatment on reducing cervical intraepitheilal neoplasia: systematic review and meta-analysis."
	
Baldini, G. M., et al. (2023). "Evaluation of the ideal vaginal Progesterone effectiveness doses for luteal support in embryo thawing cycles after endometrial preparation without using the GnRh analogue." European Review for Medical and Pharmacological Sciences 27(5): 2018-2026.
	Objective: Frozen-thawed embryo transfer (FET) cycles require the use of luteal phase support (LPS) for supporting implantation, endometrial and embryo maturity. Individualized LPS should be chosen according to the used endometrial preparation protocol. The aim of the study was to analyze the effectiveness of two different vaginal Progesterone doses for women who underwent FET cycle and the same endometrial preparation without using the GnRh analogue.; Patients and Methods: 607 women who underwent FET cycle were included in the study. 305 patients received luteal support with 600 mg/day vaginal Progesterone and 302 patients were treated with 800 mg/day of vaginal Progesterone.; Results: In the 800 mg/day group, the mean serum Progesterone concentration on the day of embryo transfer was higher than in the 600 mg group (14.00±6.18 ng/mL and 12.22±5.39, respectively, p < 0.001). Moreover, human chorionic gonadotrophin (hCG) positive and ongoing pregnancy rates were higher in the group of patients who received LPS with 800 mg/day of Progesterone than in the group of patients treated with 600 mg/day of Progesterone. CONCLUSIONS: In patients undergoing FET cycles following endometrial preparation made without previously using the GnRh analogue, 800 mg doses of vaginal Progesterone as LPS improve reproductive outcomes.

Baldini, G. M., et al. (2022). "The abortion rate in trans-myometrial eggs retrieval is the same as in classical transvaginal retrieval." European Review for Medical and Pharmacological Sciences 26(9): 3282-3288.
	OBJECTIVE: This study compares the miscarriage rate of pregnancies after trans-myometrial eggs retrieval to transvaginal eggs retrieval. PATIENTS AND METHODS: In the period between January 2004 and December 2020, 13,323 egg retrievals were carried out. In 699 cases, the ovaries were unreachable. Alternative maneuvers were performed to solve this problem, but despite this, in 132 patients the technique of trans-myometrial sampling had to be used. 26 patients were excluded from the study, because of the inclusion criteria, and therefore two groups of 106 patients were selected, Group A and Group B (control). RESULT(S): In the comparison between the two groups, there were no statistically significant differences in abortion rates, pregnancy rates and complications after the technique. CONCLUSION(S): This study shows that the abortion rate in trans-myometrial oocyte retrieval does not change when compared to classic retrieval, despite the sampling needle completely crossing the myometrium. Furthermore, the pregnancy rate and the complication rate do not appear to have worsened with this technique.Copyright © 2022 Verduci Editore s.r.l. All rights reserved.

Balears Fundació d'investigació Sanitària de les, I. and B. Islands University of the (2021). Radiofrequency and Pelvic Organ Prolapse.
	No Results Available Device: Non-ablative radiofrequency application|Other: Usual intervention Change in degree of prolapse|Changes in prolapse symptoms: bulging, pelvic heaviness and low back pain - related to POP-|Changes in quality of life|Satisfaction with treatment Female Not Applicable 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment IB4459/21PS October 23, 2022

Balemans, D., et al. (2021). Live Birth After Additional Tubal Flushing With Oil-based Contrast Versus no Additional Flushing.
	No Results Available Drug: Lipiodol Ultra Fluide® Live birth|Type of pregnancy|Number of miscarriages|Amount of pregnancy complications|Number of ectopic pregnancies|Number of clinical pregnancies|Complication during or after Hyfosy with intervention|Pain score of the Hyfosy with or without intervention|Pain score of the intervention with IMP if applicable|Thyroid function of baby|Birthweight|Gestational age at delivery|Neonatal care|Number of babies|Maternal thyroid function|General quality of life|Disease-specific quality of life|Neonatal Mortality|Major Congenital Anomaly|Gender of baby Female Phase 4 736 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment HYOIL November 1, 2024

Baliou, E., et al. (2022). "Testicular plasmacytoma. A case report and correlation with imaging findings." Virchows Archiv 481(Supplement 1): S276.
	Background & objectives: Plasmacytoma refers as a malignant plasma cell tumour growing within bones or extraosseous (extramedullary). Testicular plasmacytomas are rare malignant neoplasms with relatively poor prognosis. At the time of diagnosis, our patient did not have multiple myeloma Methods: A 87 year-old -patient presented to our hospital with a painless testicular mass, accompanied by a sense of heaviness. CT scan reveals a solid mass 6,5X5X4 cm in dimensions. An orchiectomy was the surgery of choice. On dissection of the surgical specimen, a brownish mass was recognized. Result(s): Microscopic examination showed a lesion composed entirely of mature and immature plasma cells, ranging from small and mature to large in size and atypical cells with prominent nucleoli. Sheets of plasma cells with abundant pink cytoplasm were also present invading the seminiferous tubules. Sparse, single, pale staining nuclear inclusions, with the morphologic features of "Dutcher bodies" were also present. Immunohistochemically, the neoplasm had the following profile: CD138 (+), CD19 (-), CD20 (-), CD117 (-), PLAP(-), CD56 (-), KLMW rarely (+). Confirmation of a clonal plasma cell lesion was accomplished immunohistochemically for Ig light chains. Conclusion(s): Plasmacytomas have been described in bones and in other tissues, most commonly in the upper respiratory tract with spread to cervical lymph nodes, but they may occur also in the gastrointestinal tract, breast, testis and in many other anatomical locations. Very few have been reported in the testis. Isolated testicular plasmacytoma accounts for only 0,03-0,1 %. The vast majority of patients with testicular plasmacytoma either have disseminated disease at the time of diagnosis, or develop disseminated disease later in life.

Balk, E. M., et al. (2019). "Adverse Events Associated with Nonsurgical Treatments for Urinary Incontinence in Women: a Systematic Review." Journal of General Internal Medicine 34(8): 1615-1625.
	Background: Urinary incontinence (UI) is a common malady in women. Numerous nonsurgical treatments are available, each associated with risk of adverse events (AEs). Method(s): We systematically reviewed nonsurgical interventions for urgency, stress, or mixed UI in women, focusing on AEs. We searched MEDLINE, Cochrane Central Trials Registry, Cochrane Database of Systematic Reviews, and Embase through December 4, 2017. We included comparative studies and single-group studies with at least 50 women. Abstracts were screened independently in duplicate. One researcher extracted study characteristics and results with verification by another independent researcher. When at least four studies of a given intervention reported the same AE, we conducted random effects model meta-analyses of proportions. We also assessed the strength of evidence. Result(s): There is low strength of evidence that AEs are rare with behavioral therapies and neuromodulation, and that periurethral bulking agents may result in erosion and increase the risk of voiding dysfunction. High strength of evidence finds that anticholinergics and alpha agonists are associated with high rates of dry mouth and constitutional effects such as fatigue and gastrointestinal complaints. Onabotulinum toxin A (BTX) is also associated with increased risk of urinary tract infections (UTIs) and voiding dysfunction (moderate strength of evidence). Discussion(s): Behavioral therapies and neuromodulation have low risk of AEs. Anticholinergics and alpha agonists have high rates of dry mouth and constitutional effects. BTX is associated with UTIs and voiding dysfunction. Periurethral bulking agents are associated with erosion and voiding dysfunction. These AEs should be considered when selecting appropriate UI treatment options. AE reporting is inconsistent and AE rates across studies tended to vary widely. Trials should report AEs more consistently.Copyright © 2019, Society of General Internal Medicine.

Ballav, S., et al. (2022). "PPAR-gamma Partial Agonists in Disease-Fate Decision with Special Reference to Cancer." Cells 11(20): 3215.
	Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has emerged as one of the most extensively studied transcription factors since its discovery in 1990, highlighting its importance in the etiology and treatment of numerous diseases involving various types of cancer, type 2 diabetes mellitus, autoimmune, dermatological and cardiovascular disorders. Ligands are regarded as the key determinant for the tissue-specific activation of PPAR-gamma. However, the mechanism governing this process is merely a contradictory debate which is yet to be systematically researched. Either these receptors get weakly activated by endogenous or natural ligands or leads to a direct over-activation process by synthetic ligands, serving as complete full agonists. Therefore, fine-tuning on the action of PPAR-gamma and more subtle modulation can be a rewarding approach which might open new avenues for the treatment of several diseases. In the recent era, researchers have sought to develop safer partial PPAR-gamma agonists in order to dodge the toxicity induced by full agonists, akin to a balanced activation. With a particular reference to cancer, this review concentrates on the therapeutic role of partial agonists, especially in cancer treatment. Additionally, a timely examination of their efficacy on various other disease-fate decisions has been also discussed.Copyright © 2022 by the authors.

Balsamo, R., et al. (2022). "Anterior colporrhaphy and sacrospinous hysteropexy in women with pelvic organ prolapse: Urodynamic findings and functional outcomes." European Journal of Obstetrics and Gynecology and Reproductive Biology 271: 255-259.
	Objectives: Aim of this study was to evaluate urodynamic effects and functional outcomes after anterior colporrhaphy and bilateral sacrospinous hysteropexy (SSH) in patients with stages II-IV pelvic organ prolapse (POP). Study design: This is a single-centre prospective study. Sixty-two women affected by anterior/central compartment prolapse of stage II-IV u ndergoing anterior colporrhaphy and bilateral SSH were recruited from our pelvic center. The preoperative evaluation included history, clinical examination, uroflowmetry and urodynamic studies (UDS). Six months after surgery, all patients performed UDS, completed the Urogenital Distress Inventory (UDI)-6, the Incontinence Impact Questionnaire (IIQ-7) and the Patient Global Impression of Improvement (PGI-I) questionnaire. Result(s): Median follow-up study was 11 months (range 6-24). Q max significantly improved compared with baseline (21.1 +/- 7.3 vs 12.3 +/- 7.1 ml/s; p = 0.005) and the percentage of patients with PVR > 30% of premicturitional bladder volume significantly decreased (33.3% vs 11.1%; p = 0.001). At baseline, 24 (38.7%) women had typical phasic DO. Six months after surgery, DO was detected in only eleven women (17.7%) (p < 0.0001), with no de novo cases. Thirteen (21%) women reported SUI preoperatively which persisted in 5 patients (8.1%) after surgery, with no de novo cases. BOO was observed in only eight (12.9%) patients postoperatively compared with 51 (82.3%) at baseline (p < 0.0001). At last follow up visit, the UDI-6 and IIQ-7 total median scores improved significantly (p < 0.001). Conclusion(s): Combination of anterior colporrhaphy and bilateral SSH in women with advanced POP provides good functional outcomes, as demonstrated by the urodynamic findings before and after surgery.Copyright © 2022 Elsevier B.V.

Baltacioglu, M., et al. (2023). "Does Peritoneal Metastasis Evaluation with 18F-FDG PET/ MRI Contribute to Prognosis Prediction in Patients with Ovarian Cancer." European Journal of Nuclear Medicine and Molecular Imaging 50(Supplement 1): S556.
	Aim/Introduction: The entity of peritoneal metastases in patients with ovarian cancer significantly affects the prognosis. Timely and accurate detection of ovarian cancer recurrences is important for disease survival. In this study, in patients who underwent 18F-FDG PET/CT and 18F-FDG PET/MRI for peritoneal metastasis evaluation in ovarian cancer; We aimed to compare the effects of both imaging modalities on prognosis. Material(s) and Method(s): 45 patients (median age: 58.1 years; min-max: 33-79 years) with ovarian cancer who developed elevated serum Ca-125 during follow-up after primary surgery and underwent 18F-FDG PET/ CT followed by PET/MR imaging for peritoneal disease restaging were prospectively included in this study. Peritoneal recurrences were evaluated on both imaging modalities and peritoneal carcinomatosis index (PCI) was calculated for each patient. PET/ CT and PET/MR images were evaluated on a patient basis for the presence and localization of peritoneal recurrences. After peritoneal disease staging by PET/CT and PET/MRI, patients received the treatment deemed appropriate by their clinicians and were followed up for survival analysis. The date of death was noted in exitus patients. Result(s): In patient-based analysis; PET/MRI was positive in 33 patient (73%), while PET/CT was positive in 27 patient (60%) (p=0.03). The median PCI score was 2 (min-max:0-26) in PET/CT and 4 (min-max:0-26) in PET/MRI (p<0.001). In Kaplan Meier survival analysis, FIGO stage (p<0.001), number of peritoneal lesions detected in PET/CT (p=0.017), PCI score in PET/CT (p=0.014), abdominopelvic lymph node SUVmax value in PET/CT (p=0.007), peritoneal lesion SUVmax value in PET/ MRI (p=0.035), abdominopelvic lymph node SUVmax value in PET/MRI (p=0.047) and PCI score in PET/MRI (p=0.027) were found to be parameters associated with overall survival. Conclusion(s): Although PET/MRI is more successful than PET/CT in showing peritoneal metastases, peritoneal uptake in PET/CT has been associated with prognosis. This suggests that PET/CT can be used for prognosis in patients with recurrent ovarian cancer.

Baltzer, H. (2022). "Treating post-menopausal women with symptomatic hand osteoarthritis with hormone replacement therapy." The Lancet Rheumatology 4(10): e654-e655.
	
Bambhroliya, Z., et al. (2022). "Diabetes, Polycystic Ovarian Syndrome, Obstructive Sleep Apnea, and Obesity: A Systematic Review and Important Emerging Themes." Cureus 14(6): e26325.
	Type 2 diabetes mellitus (DM), polycystic ovarian syndrome (PCOS), obstructive sleep apnea (OSA), and obesity represent four large and growing patient populations. A great deal of scientific and clinical knowledge has been developed for them individually, and significant advancements made. Taken as a group, however, the interrelationships are not as well understood. The purpose of this systematic review is to identify the body of existing research that ties them together and then to identify and discuss the prevailing themes, particularly for cause-and-effect mechanisms. PubMed, Google Scholar, and ScienceDirect were used to identify systematic reviews and meta-analysis articles to establish the broadest reach. Initially, 434 articles were carefully screened, out of which 22 most relevant studies were reviewed. Five important themes were distilled from these papers based on continued and consistent emphasis in the literature. These themes include topics such as the importance of considering visceral obesity rather than Body Mass Index (BMI), the most effective treatment approaches, including mounting support for melatonin and circadian rhythm management, the results of OSA in its feed-forward contribution to hormone imbalance, the role of non-obesity-related risk factors to PCOS and OSA such as age and genetic predisposition, and growing evidence to suggest the importance of mental health as a comorbidity in addition to the more traditional ones such as cardiovascular pathology. A new framework for investigating the interaction across these four disorders is offered that includes a revised perspective on the specific role of PCOS, perhaps being further upstream relative to the others. There currently exists a lack of well-designed randomized controlled trials in this particular area of medicine, an endeavor we believe could result in significant value, particularly as it relates to treatment approaches.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Bambhroliya et al.)

Ban, M., et al. (2024). "Association between maternal polycystic ovarian syndrome undergoing assisted reproductive technology and pregnancy complications and neonatal outcomes: a systematic review and meta-analysis." Journal of Ovarian Research 17(1): 6.
	Background: Polycystic ovarian syndrome (PCOS) is recognized as the most prevalent endocrine disorder among women of reproductive age. While the utilization of assisted reproductive technology (ART) has resulted in favorable outcomes for infertility treatment in PCOS patients, the inherent pathophysiological features of the condition give rise to complications and consequences during pregnancy and delivery for both the mother and offspring. This study was to assess the correlation between maternal PCOS and various pregnancy complications and neonatal outcomes undergone ART.; Methods: A systematic search was conducted on PubMed, EmBase, and the Cochrane Library to identify observational studies that investigated the association between PCOS and the risk of various pregnancy complications and neonatal outcomes, including gestational diabetes mellitus (GDM), hypertension in pregnancy (PIH), preeclampsia (PE), preterm birth, abortion, congenital malformations (CA), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, neonatal intensive care unit (NICU) admission and birth weight. Eligible studies were selected based on predetermined inclusion and exclusion criteria. The meta-analysis was conducted using Review Manager and Stata software, with odds ratios (ORs) or mean difference (MD), confidence intervals (CIs), and heterogeneity (I 2 ) being calculated. The search was conducted up to March 2023.; Results: A total of 33 studies with a combined sample size of 92,810 participants were identified. The findings indicate that PCOS is significantly associated with an increased risk of GDM (OR 1.51, 95% CI:1.17-1.94), PIH (OR 1.72, 95% CI:1.25-2.39), PE (OR 2.12, 95% CI:1.49-3.02), preterm birth (OR 1.29, 95% CI:1.21-1.39), and LBW (OR 1.29, 95% CI:1.14-1.47). In subgroup analyses, the risks of GDM (OR 1.80, 95% CI:1.23-2.62) and abortion (OR 1.41, 95% CI:1.08-1.84) were elevated in fresh embryo transferred (ET) subgroup, whereas elevated risk of PE (OR 1.82, 95% CI:1.17-2.83) and preterm birth (OR 1.31, 95% CI:1.21-1.42) was identified in frozen ET subgroup. Whatever with or without hyperandrogenism, patients with PCOS had a higher risk in preterm birth (OR 1.69, 95% CI: 1.31-2.18; OR 1.24, 95% CI:1.02-1.50) and abortion (OR 1.38, 95% CI:1.12-1.71; OR 1.23, 95% CI:1.06-1.43).; Conclusion: Our findings suggest that individuals with PCOS undergone ART are at a notably elevated risk for experiencing pregnancy complications and unfavorable neonatal outcomes. Nevertheless, to establish a definitive association between PCOS and pregnancy-related outcomes, it is necessary to conduct extensive prospective, blinded cohort studies and effectively control for confounding variables. (© 2024. The Author(s).)

Banas, J., et al. (2023). "Outcome of transobturator sling for treatment of female stress urinary incontinence applied as a single procedure or concomitantly with pelvic organ prolapse surgery." Annals of agricultural and environmental medicine : AAEM 30(1): 190-194.
	Introduction and Objective: The aim of the study was to check the safety and efficacy of transobturator tape (TOT) combined with various prolapse procedures. The results were compared with outcomes of sling performed as an alone surgery. Risk factors for TOT failure were also identified.; Material and Methods: The study comprised 219 patients with sling alone (Group SUI) and 221 after TOT combined with concomitant prolapse surgery (Group POP/SUI). Medical records were carefully reviewed to obtain demographic and clinical data, details of surgery, including intra-and postoperative complications.; Results: Subjective cure rate was slightly, but statistically significantly, higher in POP/SUI group (89.6% vs 82.6%; ch 2 = 4.44; p = 0.035). There was no significant difference in sling efficacy dependant of type of POP surgery. Post-operative urine retention was more frequent in POP/SUI group compared to SUI group (18.6% vs 3.2%; ch 2 = 34.36; p < 0.001). Logistic regression showed that age, BMI and prolonged pos-operative urine retention are independent factors affecting TOT outcome. Age ≥65years and BMI ≥30kg,m 2 more than doubled the risk of failure: OR 2.348, CI 95% (1.330-4.147); p = 0.003 and 2.030, (95% CI 1.148-3.587); p = 0.015; respectively. Interestingly, post-operative urine retention appeared to be a positive prognostic factor OR 0.145, (95% CI 0.019-1.097); p < 0.05.; Conclusions: Subjective efficacy of TOT used concomitantly with POP procedures is slightly higher than TOT alone. Better sling outcomes can be expected both for POP procedures involving both the anterior and posterior compartments. Age and obesity are independent factors of TOT failure, whereas prolonged post-operative urine retention is a positive predictive factor of TOT success.

Banaszewska, B., et al. (2019). "Current and future aspects of several adjunctive treatment strategies in polycystic ovary syndrome." Reproductive biology 19(4): 309-315.
	Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. PCOS is characterized by hyperandrogenism, menstrual disorders, and polycystic ovarian morphology. PCOS patients have an increased risk of type 2 diabetes, cardiovascular disease, and infertility. The mechanism of PCOS is not yet fully understood, but insulin resistance and genetic factors may play distinct roles in the pathomechanism. There is ongoing research on new therapeutic modalities for women with PCOS. In this minireview, we assessed the evidence for the effectiveness and safety of selected adjunctive agents (metformin, statins, resveratrol, melatonin, and inositols) for the treatment of women with PCOS. Metformin is a safe medication used in PCOS for 25 years that is currently recommended in select PCOS subpopulations, such as adolescents, women with metabolic disorders, and infertility infertile women undergoing ovarian hyperstimulation. Statins are also suggested in PCOS therapy, as these compounds decrease testosterone concentrations, improve lipid profiles, and ameliorate inflammatory reactions. Despite promising results, the role of statins in PCOS management needs to be further validated. Dietary supplements have also been tested in PCOS patients. Resveratrol was shown to decrease total testosterone production and improve fasting insulin but, until recently, only in one randomized study. Data on the therapeutic efficacy of melatonin and inositols on endocrine and metabolic abnormalities are limited and inconclusive. The multifactorial etiology of PCOS makes tailoring of its treatment more demanding, and there is a constant need for causative and effective modes of PCOS therapy. (Copyright © 2019. Published by Elsevier B.V.)

Banerjee, S., et al. (2022). "Title: A Randomised, Multi-centre Phase II Trial of Weekly Paclitaxel and Vistusertib in Platinum-Resistant Ovarian High-Grade Serous Carcinoma: OCTOPUS Arm 1." MedRxiv.
	Background Preclinical studies support targeting PI3K/AKT/mTOR signalling in platinum-resistant ovarian cancer (PROC). A phase I study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel (wP) showed activity. We report the results of Arm 1 of OCTOPUS, the first randomised trial of weekly paclitaxel and dual mTORC1/2 inhibition in ovarian cancer. Methods Patients with platinum-resistant or refractory high grade serous carcinoma were randomised (1:1) to wP (80mg/m2 D1,8,15 of 28 day cycle) plus oral vistusertib (50mg BD) or placebo (P). The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Results 140 patients (median age 63, range: 36-86; 18% platinum-refractory; 54% >=3 prior therapies) were randomised. There was no difference in PFS (median 4.5 vs 4.1m (HR 0.84; 80% CI (0.67, 1.07); 1-sided p=0.18), OS (median 9.7 vs 11.1m (HR 1.21; 80% CI (0.91, 1.60); 1-sided p=0.80) or RR (odds ratio 0.86; 80% CI (0.55, 1.36); 1-sided p=0.66). Grade 3/4 adverse events were 41.2% (wP+V) vs 36.7% (wP+P). Low tumour PTEN expression was associated with longer PFS in the wP+V arm (9.4 vs 4.1m p=0.003) but not in the wP arm (4.8 vs 4.2m p=0.60). Tumour genome-wide copy number (CN) analysis suggested that high CN signature 4 was associated with worse outcome in the wP+P arm (2.3 vs 4.6m p=0.018) but not the wP+V arm (5.4 vs 3.3m). Conclusions Vistusertib did not improve clinical activity of wP in PROC. However, low tumour cell PTEN expression may be a predictive biomarker for vistusertib activity.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

Banerjee, S., et al. (2022). "A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 28(21): 4634-4641.
	Purpose: CT900 is a novel small molecule thymidylate synthase inhibitor that binds to α-folate receptor (α-FR) and thus is selectively taken up by α-FR-overexpressing tumors.; Patients and Methods: A 3+3 dose escalation design was used. During dose escalation, CT900 doses of 1-6 mg/m2 weekly and 2-12 mg/m2 every 2 weeks (q2Wk) intravenously were evaluated. Patients with high-grade serous ovarian cancer were enrolled in the expansion cohorts.; Results: 109 patients were enrolled: 42 patients in the dose escalation and 67 patients in the expansion cohorts. At the dose/schedule of 12 mg/m2/q2Wk (with and without dexamethasone, n = 40), the most common treatment-related adverse events were fatigue, nausea, diarrhea, cough, anemia, and pneumonitis, which were predominantly grade 1 and grade 2. Levels of CT900 more than 600 nmol/L needed for growth inhibition in preclinical models were achieved for >65 hours at a dose of 12 mg/m2. In the expansion cohorts, the overall response rate (ORR), was 14/64 (21.9%). Thirty-eight response-evaluable patients in the expansion cohorts receiving 12 mg/m2/q2Wk had tumor evaluable for quantification of α-FR. Patients with high or medium expression had an objective response rate of 9/25 (36%) compared with 1/13 (7.7%) in patients with negative/very low or low expression of α-FR.; Conclusions: The dose of 12 mg/m2/q2Wk was declared the recommended phase II dose/schedule. At this dose/schedule, CT900 exhibited an acceptable side effect profile with clinical benefit in patients with high/medium α-FR expression and warrants further investigation. (©2022 The Authors; Published by the American Association for Cancer Research.)

Banerjee, S., et al. (2021). "Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial." The Lancet. Oncology 22(12): 1721-1731.
	BACKGROUND: There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up. METHODS: SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants. FINDINGS: Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2-24·9) in the olaparib group and 13·9 months (8·0-24·8) in the placebo group; median follow-up was 4·8 years (2·8-5·3) in the olaparib group and 5·0 years (2·6-5·3) in the placebo group. In this post-hoc analysis, median progression-free survival was 56·0 months (95% CI 41·9-not reached) with olaparib versus 13·8 months (11·1-18·2) with placebo (hazard ratio 0·33 [95% CI 0·25-0·43]). The most common grade 3-4 adverse events were anaemia (57 [22%] of 260 patients receiving olaparib vs two [2%] of 130 receiving placebo) and neutropenia (22 [8%] vs six [5%]), and serious adverse events occurred in 55 (21%) of 260 patients in the olaparib group and 17 (13%) of 130 in the placebo group. No treatment-related adverse events that occurred during study treatment or up to 30 days after discontinuation were reported as leading to death. No additional cases of myelodysplastic syndrome or acute myeloid leukaemia were reported since the primary data cutoff, including after the 30-day safety follow-up period. INTERPRETATION: For patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, after, to our knowledge, the longest follow-up for any randomised controlled trial of a PARP inhibitor in this setting, the benefit derived from 2 years' maintenance therapy with olaparib was sustained beyond the end of treatment, extending median progression-free survival past 4·5 years. These results support the use of maintenance olaparib as a standard of care in this setting. FUNDING: AstraZeneca; Merck Sharpe & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.

Banerjee, S., et al. (2021). "ATARI trial: ATR inhibitor in combination with olaparib in gynecological cancers with ARID1A loss or no loss (ENGOT/GYN1/NCRI)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(11): 1471-1475.
	BACKGROUND: ARID1A (AT-rich interactive domain containing protein 1A) loss-of-function mutations have been reported in gynecological cancers, including rarer subtypes such as clear cell carcinoma. Preclinical studies indicate that ARID1A mutant cancers display sensitivity to ATR inhibition while tumors without ARID1A mutations may be sensitive to Ataxia telangiectasia and Rad3 related (ATR) inhibitors in combination with poly-ADP ribose polymerase (PARP) inhibitors. PRIMARY OBJECTIVE: To determine whether the ATR inhibitor, ceralasertib, has clinical activity as a single agent and in combination with the PARP inhibitor, olaparib, in patients with ARID1A 'loss' and 'no loss' clear cell carcinomas and other relapsed gynecological cancers. STUDY HYPOTHESIS: ARID1A deficient clear cell carcinoma of the ovary or endometrium is sensitive to ATR inhibition, while the combination of ATR and PARP inhibition has activity in other gynecological tumors, irrespective of ARID1A status. TRIAL DESIGN: ATARI (ENGOT/GYN1/NCRI) is a multicenter, international, proof-of-concept, phase II, parallel cohort trial assessing ceralasertib activity as a single agent and in combination with olaparib in ARID1A stratified gynecological cancers. Patients with relapsed ovarian/endometrial clear cell carcinoma with ARID1A loss will receive ceralasertib monotherapy (cohort 1A). Relapsed ovarian/endometrial clear cell carcinoma patients with no ARID1A loss (cohort 2) or patients with other histological subtypes (endometrioid, carcinosarcoma, cervical) (cohort 3) will receive combination therapy (olaparib/ceralasertib). Treatment will continue until disease progression. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with histologically confirmed recurrent clear cell (ovarian, endometrial, or endometriosis related), endometrioid (ovarian, endometrial, or endometriosis related), cervical (adenocarcinomas or squamous), or carcinosarcomas (ovarian or endometrial) are eligible. Patients progressing after ≥1 prior platinum with evidence of measurable (RECIST v1.1) radiological disease progression since last systemic anticancer therapy and prior to trial entry are eligible. Previous ATR or PARP inhibitor treatment is not permissible. PRIMARY ENDPOINT: Best overall objective response rate (RECIST v1.1). SAMPLE SIZE: A minimum of 40 and a maximum of 116. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is anticipated to be complete by the second quarter of 2022, with reporting of results by the fourth quarter of 2022. Overall accrual targets and reporting timelines are dependent on individual cohort progression to stage 2. TRIAL REGISTRATION NUMBER: NCT0405269.

Banerjee, S. N., et al. (2022). "ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of VS-6766 (RAF/MEK clamp) alone and in combination with defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC)." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Low-grade serous ovarian cancer (LGSOC) constitutes up to 10% of all ovarian cancer and has clinical and molecular characteristics distinct from high-grade serous ovarian cancer. Approximately a third of patients (pts) with recurrent LGSOC harbor KRAS mutations (mt) and pts with KRAS wild-type (wt) LGSOC may have mutations in NRAS, BRAF, or other RAS pathway-associated genes. Prior clinical studies with single agent MEK inhibitors have shown response rates of 16-26% in recurrent LGSOC. VS-6766 is a unique small molecule RAF/MEK clamp that inhibits both RAF and MEK activities by trapping them in inactive complexes. This mechanism of blockade has been shown to limit compensatory MEK activation, thereby potentially enhancing efficacy of MEK inhibition. Focal adhesion kinase (FAK) activation is a putative resistance mechanism to RAF and MEK inhibition, and defactinib, a small molecule inhibitor of FAK, has shown synergistic anti-tumor activity with VS-6766 in preclinical models, including organoids from LGSOC pts. Furthermore, FAK inhibition combined with VS-6766 induces tumor regression in a KRAS mt ovarian cancer xenograft model. The combination of VS-6766 and defactinib is currently being evaluated in the ongoing Investigator Sponsored FRAME study (NCT03875820). In this proof-of-concept study, durable objective responses (ORR = 46%; 11/ 24) have been reported in recurrent LGSOC pts, including pts who have had a prior MEK inhibitor (Banerjee ESMO 2021) and the combination of VS-6766 + defactinib has received FDA Breakthrough Therapy Designation for recurrent LGSOC. These initial preclinical and clinical results support the ongoing phase 2 ENGOT-ov60/GOG-3052 in recurrent LGSOC. Method(s): This is an international phase 2, adaptive, multicenter, randomized, open label study designed to evaluate the efficacy and safety of VS-6766 vs VS-6766 in combination with defactinib currently open to enrollment (NCT04625270). The study will be conducted in two parts. Part A will determine the optimal regimen based on confirmed overall response rate (independent radiology review) in KRAS mt and KRAS wt LGSOC. Part B will determine the efficacy of the optimal regimen identified in Part A in KRAS mt and KRAS wt LGSOC. The minimum expected enrollment is 104 pts, 52 pts with KRAS mt and 52 KRAS wt (64 pts in Part A and 40 pts in Part B). Pts will be randomized to receive VS-6766 (4.0 mg orally (PO), twice weekly 3 wks on, 1 wk off) or VS-6766 with defactinib (VS-6766 3.2 mg PO, twice weekly + defactinib 200 mg PO BID 3 wks on, 1 wk off) till progression. Key inclusion criteria include histologically confirmed LGSOC, known KRAS mutation status, prior systemic therapy including platinum for metastatic disease and up to 1 prior line of MEK inhibitor therapy permitted. Part A of this study has completed enrollment and Part B is currently enrolling pts.

Bang, Y. J., et al. (2024). "Analgesic efficacy of erector spinae plane block in patients undergoing major gynecologic surgery: A randomized controlled study." Journal of Clinical Anesthesia 93: 111362.
	Study objective: To investigate the analgesic efficacy of erector spinae plane block (ESPB) in major gynecologic surgery, expressed as cumulative opioid consumption 24 h after surgery. Design(s): A single-center, patient-assessor blinded, randomized controlled study. Setting(s): Samsung medical center (tertiary university hospital), between February 2022 to January 2023. Patient(s): Eighty-eight females undergoing major surgery with long midline incision for gynecologic malignancy. Intervention(s): Patients were randomly assigned to receive standard systemic analgesia (Control group) or ESPB (ESPB group). ESPB was performed bilaterally at the level of the 9th thoracic vertebra with a mixture of 20 mL of 0.5% ropivacaine and 100 mug of epinephrine. Measurements: The primary outcome was cumulative opioid consumption at 24 h postoperatively. Secondary outcomes included opioid consumption and pain severity during the 72 h after surgery. The variables regarding postoperative recovery and patient-centered outcomes were compared. Main Result(s): The mean cumulative opioid consumption 24 h after surgery was 35.8 mg in the ESPB group, which was not significantly different from 41.4 mg in the control group (mean difference, 5.5 mg; 95% CI -1.7 to 12.8 mg; P = 0.128). However, patient satisfaction regarding analgesia was significantly higher in the ESPB group compared with the control group at 24 h postoperative (median difference, -1; 95% CI -3 to 0; P = 0.038). There were no significant differences in the variables associated with postoperative recovery. Conclusion(s): ESPB did not reduce opioid consumption during the 24 h postoperative but attenuated pain intensity during the early period after surgery.Copyright © 2023 Elsevier Inc.

Bang Yu, J., et al. (2023). "The Effect of Intrathecal Morphine on Postoperative Opioid Consumption in Patients Undergoing Abdominal Surgery for Gynecologic Malignancy: A Randomized Sham-Controlled Trial." Anesthesia and analgesia 137(3): 525-533.
	Background: Surgery for gynecologic malignancy via midline-laparotomy leads to severe postoperative pain. Adequate pain control while sparing opioid consumption does offer benefits in postoperative complications and recovery. Intrathecal morphine (ITM) provides simple and effective analgesia. In this randomized trial, we compared postoperative opioid consumption in patients who received either ITM or a sham procedure.; Methods: We enrolled 68 adult patients undergoing open gynecologic oncology surgery from June 2021 to November 2021. They were randomly allocated to the ITM group (ITM; 200 μg injection) or sham group (sham procedure) to achieve a final 1:1 ratio between groups. We compared opioid consumption and pain severity during 72 hours after surgery. The variables regarding postoperative recovery and patient-centered outcomes were collected. The primary outcome is cumulative intravenous (IV) opioid consumption 24 hours after surgery.; Results: The median (interquartile range) cumulative IV opioid consumption during 24 hours after surgery was 18 mg (12-29) in the ITM group and 36 mg (27-42) in the sham group (median difference, 13; 95% confidence interval, 7.2-20.7; P < .001). Patient satisfaction regarding pain control was statistically significantly higher in the ITM group than in the sham group at postoperative 24 and 48 hours ( P < .001 and P = .005, respectively). There were no significant differences in the variables associated with postoperative recovery and frequency of complications requiring treatment.; Conclusions: ITM is a safe and effective analgesic method after curative intent laparotomy for gynecologic malignancy. ITM provides better pain relief, reduces opioid consumption, and improves patient satisfaction without additional evident adverse events.; Competing Interests: The authors declare no conflicts of interest. (Copyright © 2023 International Anesthesia Research Society.)

Bánhidi, A. and Z. Novák (2022). "[Robotic surgery in gynecologic cancer, especially in cervical cancer]." Magyar onkologia 66(4): 295-301.
	The development of robotic surgery is another step in the evolution of modern surgery. Robot-assisted minimally invasive procedures undoubtedly have many advantages compared to traditional laparotomy, which is why they have also been introduced in the treatment of gynecological cancers. Numerous studies have confirmed the advantages of robotic surgery in terms of quicker recovery, reduced blood loss, and shorter hospitalization. The technique provides a significant advantage in the minimally invasive treatment of overweight patients. However, in the treatment of cervical cancer, the use of minimally invasive procedures have declined in recent years due to worse oncological results. It is necessary to carry out further clinical trials in this indication using surgical solutions that prevent the spread of the tumor, in order to find out whether minimally invasive surgery regains its important role in the surgical treatment of early cervical cancer.

Bansal, K., et al. (2023). "Herbal Medicines - a Fruitful Approach to Periodic Illness Dysmenorrhoea: Evidence-based Review." Current pharmaceutical biotechnology.
	Dysmenorrhea (menstrual or periodic pain) is a discomfort that occurs during painful periods. It is the first and most prominent reason for female lower abdominal pain. Most adolescent girls consider it a curse due to the periodic occurrence of painful cramps and bleeding. The pathogenesis of painful periods is most likely because of increased prostanoids, notably prostaglandins, produced by the cyclooxygenase pathway (PGs). Misuse of synthetic medications leads to the development of medication resistance and deposits toxic residues in the body; thus, there is a critical need for safe and effective alternatives. In recent decades, herbal treatment approaches have found extensive applications in the treatment of various ailments. Herbal therapies are an alternate source, which include several bioactive chemicals, and recent improvements in our understanding of the value of herbal therapy methods have caused a sharp rise in their production. The main focus of this review was to study herbal treatment options; the recent studies conducted on herbal therapies and various experimental investigations on dysmenorrhea and herbal therapy methods have been studied, and randomized controlled trials and animal models have been discussed describing the anti-inflammatory properties of some potential herbal medicines that can be used as treatment options for dysmenorrhoea. This review aimed to present herbal treatments that can be used as alternative traditional synthetic medications and oral hormonal contraceptives in the treatment of painful menstruation. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bantum, E. O., et al. (2023). "Hula as a physical activity and social support intervention for sustained activity in female breast and gynecologic cancer survivors." Frontiers in psychology 14: 1190532.
	BACKGROUND: Physical activity improves health and psychosocial functioning for people who have been diagnosed with cancer. Native Hawaiians face disparities for some cancers, including breast cancer. Delivering culturally grounded interventions has the potential to improve enjoyment and adherence to the intervention. We sought to test the adherence and impact of a 6 month randomized wait-list controlled trial of hula. METHODS: In this randomized wait-list controlled design people who had been diagnosed with breast or gynecologic cancers were invited to participate with other cancer survivors in a group based setting. Participants were randomized to begin hula immediately or after six months. Attendance was collected and heart-rate measured three times per session. In addition, demographic data, self-report psychosocial data, and biological data (findings will be reported elsewhere) were collected at three time points: baseline, 6 months, and 12 months. The study included six months of hula, twice per week, 60 min each session. In addition, participants committed to practice 60 min per week at home. RESULTS: Participants in the study (n = 42) attended, on average, 72% of the sessions. Significant increase in moderate physical activity (d = 0.50, p = 0.03) was observed in the intervention versus control group. For the measures of intra-individual changes pre-and post-intervention, an increase in total physical activity were seen in the intervention group (d = 0.69, p = 0.003), daily caloric intake decreased (d = -0.62, p = 0.007), and a reduction in waist circumference (d = -0.89, p = 0.0002) that was sustained six months after completion of the intervention. Psychosocially, cognitive functioning significantly declined from baseline to 12 months (d = -0.50, p = 0.03), with role functioning improving (d = 0.55, p = 0.02), social constraints increasing (d = 0.49, p = 0.03), and financial difficulties improving (d = -0.55, p = 0.02). CONCLUSION: Sustainable physical activity is crucial to improve both the survival and quality of life of cancer survivors. Culturally grounded interventions, such as hula have the potential to increase the maintenance of physical activity. In addition, they create a support group where the benefits of people who have all experienced cancer can gather and garner those benefits of social support, too. This study was registered as a clinical trial through the National Cancer Institute (NCT02351479). CLINICAL TRIAL REGISTRATION: Clinicaltrails.gov, NCT02351479.

Banys-Kotomska, J., et al. (2023). "Physical activity and pelvic floor muscle training during pregnancy: review of international recommendations." Ginekologia polska.
	Physical activity is associated with beneficial health effects for both mother and her future child, as well as the course of pregnancy. The aim of this review was the comparison of international guidelines with Polish recommendations. Data were collected from PubMed platform and international guidelines and narrowed to open access studies published between 1990-2023 in English, German and Polish. The existing literature shows an increase of interest in the impact of body activity during pregnancy and pelvic floor muscle training (PFMT). The recommendations move away from the more conservative approach, that previously suggested limitation of all exercise-related activities. Recently, The Polish Society of Gynecologists and Obstetricians and Polish Society of Sports Medicine announced a planned release of joint recommendations on physical activity during pregnancy and after childbirth, as well as the translation of the "Get Active Questionnaire for Pregnancy", a screening tool for pregnant women, doctors and midwives, developed in accordance with the recommendations of international gynecological societies.

Bao, T., et al. (2021). "Health-Related Quality of Life in Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy: A Randomized Clinical Trial." The Oncologist 26(11): e2070-e2078.
	BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating adverse effect of neurotoxic chemotherapy that significantly worsens the quality of life of cancer survivors. MATERIALS AND METHODS: Survivors of solid tumors with persistent moderate-to-severe CIPN defined as numbness, tingling, or pain rated ≥4 on an 11-point numeric rating scale (NRS) were randomized in a 1:1:1 ratio to 8 weeks of real acupuncture (RA) versus sham acupuncture (SA) versus usual care (UC). We previously reported the primary endpoint (NRS); here we report the following health-related quality of life endpoints: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Brief Fatigue Inventory (BFI). For each endpoint, the mean changes from baseline and 95% confidence intervals were estimated within each arm and compared between arms using linear mixed models. RESULTS: We enrolled 75 survivors of solid tumors with moderate-to-severe CIPN into the study. Compared with baseline, at week 8, FACT/GOG-Ntx, HADS anxiety, and ISI scores significantly improved in RA and SA, but not in UC. Compared with UC, at week 8, FACT/GOG-Ntx scores significantly increased in RA and SA arms indicating improved CIPN-related symptoms and quality of life (p = .001 and p = .01). There was no statistically significant difference between RA and SA. There was no difference in HADS depression or BFI among RA, SA, and UC at weeks 8 and 12. CONCLUSION: Acupuncture may improve CIPN-related symptoms and quality of life in cancer survivors with persistent CIPN. Further large sample size studies are needed to delineate placebo effects. IMPLICATIONS FOR PRACTICE: The authors conducted a randomized sham acupuncture- and usual care-controlled clinical trial to evaluate the impact of acupuncture on health-related quality of life outcomes in patients with solid tumors with chemotherapy-induced peripheral neuropathy (CIPN). Statistically significant improvements in quality of life, anxiety, insomnia, and fatigue were achieved with 8 weeks of real acupuncture when compared with baseline, without statistically significant differences between real and sham acupuncture. These findings suggest that acupuncture may be effective for improving CIPN-related symptoms and quality of life and reducing anxiety and insomnia in cancer survivors with persistent CIPN, with further study needed to delineate placebo effects.

Bao, W. and Z. Li (2024). "Efficacy and safety of neoadjuvant chemotherapy containing anti-angiogenic drugs, immunotherapy, or PARP inhibitors for ovarian cancer." Critical Reviews in Oncology/Hematology 194: 104238.
	Ovarian cancer is the most lethal gynecologic malignancy. The standard treatment involves chemotherapy with platinum-paclitaxel following cytoreductive surgery. For patients battling widespread and aggressive tumor spread, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery emerges as an encouraging alternative. However, the effectiveness of this strategy is often limited by advanced-stage diagnosis and high likelihood of recurrence. The high mortality rate necessitates the exploration of targeted therapies. Present results signal promising efficacy and acceptable toxicities of anti-angiogenic drugs, immunotherapy, or PARP inhibitors used in chemotherapy. However, the potential integration of these drugs into NACT raises questions about response rates, surgical outcomes, and adverse events. This review delves into the findings from all published articles and ongoing studies, aiming to summarize the clinical use of anti-angiogenic drugs, immunotherapy, or PARP inhibitors in NACT, highlight the positive and negative aspects, and outline future perspectives.; Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bao, X., et al. (2021). "Meta-analysis on current status, efficacy, and safety of laparoscopic and robotic ventral mesh rectopexy for rectal prolapse treatment: can robotic surgery become the gold standard?" International Journal of Colorectal Disease 36(8): 1685-1694.
	Purpose: Robotic-assisted surgery and robotic-assisted ventral mesh rectopexy are gaining attention in the treatment of rectal prolapse and increased positive findings are proposed. The objective of this meta-analysis was to investigate whether robotic-assisted ventral mesh rectopexy is comparable with the conventional laparoscopic approach surgery.; Methods: Five major databases (PubMed, Sciencedirect, Web of Science, Embase, and Cochrane Library) were searched for eligible studies. Observational studies of the effect and safety of robotic-assisted and laparoscopic approaches on ventral mesh rectopexy were included. Odd ratios (OR) and weight mean difference (WMD) were used for dichotomous data and continuous data analysis. Clinical outcomes, functional outcomes, and cost-effectiveness data were extracted for meta-analysis.; Results: Compared to the laparoscopic approach, a significant shorter length of hospital stay (LOS), lesser intraoperative blood loss, and lower post-operative complication rate of RVMR group were observed. However, operation time of RVMR was significant increased. The expense of RVMR was higher than LVMR; mean Wexner scores and fecal incontinence were lower in RVMR group while there were no statistical differences.; Conclusion: The result of the current analysis revealed that the robotic-assisted ventral mesh rectopexy is effective and feasible in the treatment of rectal prolapse. However, long-term follow-up and results are needed for the promotion of this approach. There is a long way for robotic-assisted surgery to become a gold standard in rectal surgery. (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Barachisio, L., et al. (2023). "Transobturator Versus Minisling for Urinary Incontinence: A Randomized Controlled Trial." Urogynecology (Philadelphia, Pa.).
	IMPORTANCE: The comparison between single-incision slings (SISs) and midurethral slings has been documented in the literature, but results vary according to the SIS device. OBJECTIVE(S): The purpose of this study is to assess whether SIS (Solyx) is noninferior to transobturator (TOT) (Obtryx) sling for treating women with confirmed stress-predominant urinary incontinence. STUDY DESIGN: A prospective, parallel, nonblinded, multicenter, noninferiority, randomized controlled study with 114 patients were randomized and followed 6 and 12 months after surgery. Interventions were midurethral TOT sling (Obtryx-halo; n = 58) or SIS (Solyx; n = 56). The primary outcome was improvement in the Patient Global Impression of Improvement (PGI-I). Secondary outcomes were the Kings Health Questionnaire (KHQ) instruments after treatment, subjective improvement, and surgical outcomes. RESULT(S): Both groups were homogeneous (P = NS) regarding sociodemographic and clinical variables. There was improvement in the PGI-I after 6 (P = 0.001) and 12 months (P = 0.001) of treatment for women who underwent TOT sling. After 6 months, KHQ scores improved in the TOT group for the following domains: role limitations (P = 0.026) and physical limitations (P = 0.006). After 12 months, the TOT group presented better KHQ scores that were statistically significant from the SIS group in incontinence impact (P = 0.012), physical limitations (P = 0.001), and severity measures (P = 0.017). Moreover, the TOT group presented higher subjective improvement after 6 months (P = 0.006) than the SIS group. Mesh erosion was higher in the SIS group (P = 0.006). Reoperations were not statistically different between groups. CONCLUSION(S): There were higher scores in the PGI-I score and higher subjective improvement for the TOT sling after 6 and 12 months of treatment when compared with the SIS group.Copyright © 2023 American Urogynecologic Society. All rights reserved.

Baradwan, S., et al. (2023). "What is the effect of sildenafil citrate intake on women undergoing assisted reproduction? A systematic review and meta-analysis of randomized controlled trials." Turkish Journal of Obstetrics and Gynecology 20(4): 293-313.
	Assisted reproductive technologies (ART) have become a vital option for women facing fertility challenges. One of the potential interventions being explored is the use of sildenafil citrate (SC) to improve clinical outcomes in ART procedures. The aim of this study was to assess the impact of SC on clinical outcomes in women undergoing ART. A comprehensive literature search was conducted using multiple databases, including PubMed, Scopus, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. The search covered studies from inception until April 15, 2023, and identified relevant randomized controlled trials (RCTs) for inclusion in the analysis. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). After meticulous analysis, twenty-eight RCTs comprising 3,426 women were included in the study. The results revealed significant findings regarding the impact of SC on clinical pregnancy (CP) rates. Women receiving SC demonstrated a significantly higher probability of CP compared to the control group (n=21 RCTs, RR=1.43; 95% CI: 1.29, 1.59). Additionally, when SC was combined with other medications like clomiphene citrate (CC) or estradiol valerate, it further improved the likelihood of CP compared to these medications alone (RR=1.35, 95% CI: 1.19, 1.53; RR=1.55, 95% CI: 1.08, 2.22, respectively). Furthermore, the study observed that the mean endometrial thickness (ET) was significantly higher in women who received SC compared to the control group, which involved other active interventions or placebo (SMD=0.77, 95% CI: 0.20, 1.34). Particularly, the administration of SC resulted in a notably higher ET level compared to the placebo (SMD: 1.33, 95% CI: 0.15, 2.51). The findings suggest that luteal supplementation of SC can be considered a beneficial approach to enhance ET and improve the CP rate in women undergoing ART.

Baradwan, S., et al. (2023). "The Effect of Endometrial Scratch on Pregnancy Rate in Women with Previous Intrauterine Insemination Failure: a Systematic Review and Meta-analysis of Randomized Controlled Trials." Reproductive sciences (Thousand Oaks, Calif.) 30(5): 1399-1407.
	The objective of this study was to evaluate the impact of endometrial scratch on the pregnancy rate among women with previous failed intrauterine insemination (IUI). A systematic search was done in PubMed, Cochrane Library, Scopus, and ISI web of science from inception to November 2021. We selected randomized clinical trials (RCTs) that compared endometrial scratch in the intervention group versus placebo or no intervention in the control group among infertile women with previous failure of IUI regarding different pregnancy outcomes. Revman software was utilized for performing our meta-analysis. Our main outcomes were biochemical pregnancy, clinical pregnancy, and live birth rates. Five RCTs met our inclusion criteria with a total number of 989 patients. We found endometrial scratch significantly improved the biochemical and clinical pregnancy rates in comparison with the control group among women with previous IUI failure (p < 0.001). Moreover, the live birth rate was significantly increased among the endometrial scratch group (RR = 2.00, 95% CI [1.20, 3.34], p = 0.008). In conclusion, endometrial scratch is effective in improving pregnancy outcomes among women with previous IUI failure. More trials are required to confirm our findings. (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Baradwan, S., et al. (2021). "Ultrasound guidance versus classical method for intrauterine insemination: A systematic review and meta-analysis of randomized controlled trials." European Journal of Obstetrics, Gynecology, and Reproductive Biology 263: 223-230.
	Objective: There is a great controversy regarding the benefits of ultrasound-guided intrauterine insemination (IUI) in improving pregnancy rates. Thus, we aimed to compare ultrasound-guided IUI versus classical IUI regarding the pregnancy rates improvement.; Methods: A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus during June 2021. We selected randomized clinical trials (RCTs) that compared ultrasound-guided IUI versus classical IUI in different pregnancy outcomes. We extracted the available data from included studies and pooled them in a meta-analysis model using RevMan software. Our primary outcome was clinical pregnancy rate. Our secondary outcomes were miscarriage, live birth rates, and incidence of difficulty reported during the procedure. The overall quality of evidence was assessed through GRADEpro GDT software.; Results: Seven RCTs met our inclusion criteria with a total number of 1338 patients. We found that ultrasound-guided IUI significantly improved the clinical pregnancy rate when compared to the classical group (RR = 1.33, 95% CI [1.05, 1.68], p = 0.02). However, there were no significant differences between both groups in terms of miscarriage and live birth rates. Ultrasound-guided IUI significantly reduced the incidence of difficulty reported during the procedure (RR = 0.42, 95% CI [0.21, 0.84], p = 0.01). The GRADEpro GDT tool showed high quality of evidence for the evaluated outcomes.; Conclusions: There is evidence of high quality that ultrasound-guided IUI improves the pregnancy rate and reduces the incidence of difficulty reported during the procedure.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Baradwan, S., et al. (2024). "Effects of letrozole alone or in combination with gonadotropins on ovulation induction and clinical pregnancy in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials." Hormones.
	Objective: To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS). Method(s): Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter >= 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS). Result(s): Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome. Conclusion(s): Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.Copyright © 2024, The Author(s), under exclusive licence to Hellenic Endocrine Society.

Baradwan, S., et al. (2022). "Prophylactic tranexamic acid during myomectomy: A systematic review and meta-analysis of randomized controlled trials." European Journal of Obstetrics and Gynecology and Reproductive Biology 276: 82-91.
	Objective: To conduct a systematic review and meta-analysis of randomized controlled trials on the clinical efficacy and safety of prophylactic tranexamic acid (TXA) versus control (normal saline/no treatment) during myomectomy. Method(s): Six databases were screened from inception until 21-February-2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. Result(s): Seven studies, comprising eight arms and 571 patients (TXA = 304 patients, control = 267 patients) were analyzed. The included studies had an overall low risk of bias. The mean intraoperative blood loss (MD = -224.34 ml, 95% CI [-303.06, -145.61], p < 0.001), mean postoperative blood loss, and mean total blood loss were significantly reduced in favor of the prophylactic TXA group. Additionally, the mean postoperative hemoglobin (MD = 0.4 mg/dl, 95% CI [0.11, 0.68], p = 0.006) and mean postoperative hematocrit levels were significantly higher in favor of the prophylactic TXA group. While the mean hospital stay was significantly reduced in favor of the prophylactic TXA group (MD = -0.39 d, 95% [-0.74, -0.04], p = 0.03), there was no significant difference between both groups regarding the mean operation time and rate of blood transfusion. None of the participants in both groups developed any incidence of thromboembolic events. The rate of nausea was significantly higher in disfavor of the prophylactic TXA group (RR = 2.68, 95% CI [1.11, 6.43], p = 0.03). Conclusion(s): Among patients undergoing myomectomy, prophylactic TXA was largely safe and linked to substantial reductions in perioperative blood loss and related morbidities.Copyright © 2022 Elsevier B.V.

Barahona, V. I. A., et al. (2024). "EFFICACY OF HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY IN OVARIAN CANCER IN ADULT WOMEN (RS)." Journal of Population Therapeutics and Clinical Pharmacology 31(1): 1054-1064.
	Context: In ovarian cancer, cytoreductive surgery is the treatment of choice, followed by adjuvant chemotherapy; where, hyperthermic intraperitoneal chemotherapy controls residual disease, with the combination of physical (thermal) and chemical (chemotherapeutic) methods prior to the formation of adhesions. Objective(s): To determine the efficacy of hyperthermic intraperitoneal chemotherapy in ovarian cancer in adult women. Procedures: Systematic review of primary studies published in PubMed, Scopus and Web of Science from 2013 to 2023, in Spanish and English. Result(s): A total of 133,393 articles were obtained, 108 were selected after the first reading, later considering the inclusion and exclusion criteria, 9 studies were used for the present review. The categories hyperthermic intraperitoneal chemotherapy, Cytoreductive Surgery, Survival, Endothelial Ovarian Cancer are described. Conclusion(s): Research results support the efficacy of HIPEC as a promising therapeutic approach for ovarian cancer treatment., demonstranting an overall survival of 35 months and progression - free survival of 15.6 months.Copyright © 2024, Codon Publications. All rights reserved.

Barakat, B., et al. (2020). "A systematic review and meta-analysis of clinical and functional outcomes of artificial urinary sphincter implantation in women with stress urinary incontinence." Arab Journal of Urology 18(2): 78-87.
	Objective: To evaluate the complications and results of artificial urinary sphincter (AUS) implantation in women with stress urinary incontinence (SUI). Method(s): A selective database search using keywords (1990-2019) was conducted to validate the effectiveness of the AUS in women. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilised. The meta-analysis included 964 women (15 studies) with persistent SUI. The Newcastle-Ottawa score was used to determine the quality of the evidence in each study. The success rate and complications associated with the AUS were analysed. Result(s): Meta-analysis of the published studies showed that complete continence was achieved at a mean rate of 79.6% (95% confidence interval [CI] 72.2-86.6%) and a significant improvement was achieved in 15% (95% CI 10-25%). The mean (range) follow-up was 22 (6-204) months. The mean number of patients per study was 68. The mean (range) explantation rate was 13 (0-44)%. Vaginal erosion occurred in a mean (range) of 9 (0-27)% and mechanical complications in 13 (0-47)%. Infections accounted for 7% of the complications. The total mean (range) revision rate of the implanted AUS was 15.42 (0-44)%. The mean (range) size of the cuff used was 6.7 (5-10) cm. Conclusion(s): Our present analysis showed that implantation of an AUS in women with severe UI is an effective treatment option after failure of first-line therapy. However, the currently available study population is too small to draw firm conclusions. Abbreviations: AMS: American Medical Systems; AUS: artificial urinary sphincter; EAU: European Association of Urology; LE: Level of Evidence; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; QoL: quality of life; SHELTER: Services and Health for Elderly in Long TERm care (study); SUI: (stress) urinary incontinence.Copyright © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Barakat, B., et al. (2020). "Stem cell applications in regenerative medicine for stress urinary incontinence: A review of effectiveness based on clinical trials." Arab Journal of Urology 18(3): 194-205.
	Objective: To evaluate the current state, therapeutic benefit and safety of urethral injection of autologous stem cells for the treatment stress urinary incontinence (SUI). Material(s) and Method(s): A selective database search of PubMed, the Excerpta Medica dataBASE (EMBASE), Cochrane Library and Google Scholar was conducted to validate the effectiveness of stem cell-based therapy. The search included clinical trials published up until 4 January 2020, written in English, and included cohorts of women and men who had received stem cell-based therapy for SUI. The search used the following keywords in various combinations: 'stem cell therapy', 'cell-based therapy for SUI', 'regenerative medicine for SUI', and 'tissue engineering'. The success rates were assessed according to cough test, urodynamics, pad tests, and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The primary endpoint was continence rate to measure objectively the effect of the treatment. Result(s): We identified four clinical trials using local injections of adipose-derived stem cells (ADSCs), 11 trails with muscle-derived stem cells (MDSCs), and two trails with human umbilical cord blood stem cells (HUCBs) and total nucleated cells (TNCs). The median improvement rate of intrinsic sphincter deficiency after ADSCs, MDSCs, TNCs, HUCBs injections were 88%, 77%, 89%, 36% (improvement rate: 1-2 pads) at a mean (range) follow-up of 6 (1-72) months. The cell sources, methods of cell processing, cell number, and implantation techniques differed considerably between studies. Most of the periurethral injections were at the 3, 5, 7, and 9 o'clock positions and for submucosa were at the 4, 6, and 8 o'clock positions. No significant postoperative complications were reported. Conclusion(s): Despite many challenges in stem cell-based therapy for treating SUI, it appears to provide, in both male and female patients, acceptable functional results with minimal side-effects and complications. In the future, more clinical trials should be funded in order to optimise stem cell-based therapy and evaluate long-term outcomes. Abbreviations: ADSC: adipose-derived stem cell; BMSCs: bone marrow-derived mesenchymal stem cell; CLPP: cough leak-point pressure; FPL: functional profile length; HUCB: human umbilical cord blood stem cell; ICIQ-(QOL)(SF)(UI): International Consultation on Incontinence Questionnaire (Quality of life) (-Urinary incontinence Short Form) (-Urinary Incontinence); IIQ-7: Incontinence Impact Questionnaire-short form; I-QOL: Incontinence quality of life questionnaire; ISD: intrinsic urinary sphincter deficiency; MDSC: muscle-derived stem cell; MUCP: maximum urethral closure pressure; NR: not reported; Pdet-max: maximum detrusor pressure; PVR: post-void residual urine volume; Qmax: maximum urinary flow; QOL: quality of life; RP: radical prostatectomy; TNC: total nucleated cell; (S)UI: (stress) urinary incontinence; UDSCs: urine-derived stem cells; UTUS: upper tract ultrasonography; VLPP: Valsalva leak-point pressure.Copyright © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Barba, M., et al. (2021). "Stem cells in clinical trials for pelvic floor disorders: A systematic literature review." Neurourology and Urodynamics 40(SUPPL 3): S99-S100.
	Introduction and aim of the study: Pelvic floor disorders (PFDs) include a series of conditions that can be poorly tolerated, negatively affecting the quality of life. Current treatment options pelvic floor rehabilitation and subsequent surgical repair in case of conservative therapy failure [1]. Regenerative medicine might offer an alternative treatment strategy. Stem cells (SCs) represent a promising tool for tissue engineering, in particular for skeletal and connective tissue repair [2]. This systematic review aims to define the state of art of SC therapy for PFDs in clinical trials, by systematically reviewing the best available evidence. Material(s) and Method(s): A systematic search strategy was conducted up to Nov 7, 2020 in PubMed, Scopus, Cochrane Library, and ISI Web of Science. Preclinical studies on animal models were not considered. Studies were included when the patients were affected by any PFDs and cells were isolated, cultured, and characterized as SC. The study protocol was registered in PROSPERO (CRD42020216551). Result(s): A total of 11 prospective clinical studies were included in the final assessment. Specifically, 7 single-arm studies dealing with SC therapy for urinary incontinence and 4 with anal incontinence. No papers concerning the use of SC for prolapse repair were retrieved. Due to the great heterogeneity, data pooling was not possible. Interpretation of results: The number of patients who underwent SCs therapy was limited. Regarding stem cells injection for urinary incontinence therapy, studies with muscle-derived stem cells or with human cord blood stem cells reported a higher benefit in terms of patient satisfaction [3]. At the same time, stem cell therapy for anal incontinence showed promising results with the use of muscle-derived stem cells in terms of objective, subjective, and instrumental functional findings. Stem cell injection resulted in a safe procedure, with few and mild adverse effects, mostly related to harvesting sites. Unfortunately, due to great heterogeneity in terms of study design, inclusion criteria, stem cells harvesting/ delivery, outcome measures, and timepoints, data pooling was not possible. Conclusion(s): This review highlighted that SC therapy for PFDs is a safe procedure, but there is no clear evidence of its efficacy. Further larger targeted studies with control arms are needed before any conclusions can be made. (Table Presented).

Barba, M., et al. (2021). "Obstetric outcomes after uterus-sparing surgery for uterine prolapse: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 256: 333-338.
	Up-to-date there are no guidelines about uterus-sparing prolapse repair procedures for women desiring childbearing. This systematic review and meta-analysis aims to evaluate obstetrical outcomes after uterus-sparing apical prolapse repair in terms of pregnancy rate, obstetrical adverse outcomes and delivery mode according to the type of procedure. To identify potentially eligible studies, we searched PubMed, Scopus, Cochrane Library and ISI Web of Science (up to April 15, 2020). Case reports, reviews, letters to Editor, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded. Twenty-four studies met inclusion criteria and were incorporated into the final assessment, which included 1518 surgical procedures. In total 151 patients got pregnant after prolapse surgical repair, for a resulting pregnancy raw rate of 9.9 %. Overall, adverse obstetric outcomes resulted low, rating 4.6 %. Manchester procedure resulted associated with the highest risk of adverse obstetrical outcomes and preterm premature rupture of membranes (p < 0.0001). After exclusion of Manchester procedure, sacrohysteropexy was found to be associated with higher risk of obstetrical adverse outcomes compared to native-tissue procedures (p = 0.04). Native-tissue surgery might represent the most cautious option for women wishing for pregnancy.; Competing Interests: Declaration of Competing Interest The authors report no declarations of interest. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Barber, K. and A. Charles (2023). "Barriers to Accessing Effective Treatment and Support for Menopausal Symptoms: A Qualitative Study Capturing the Behaviours, Beliefs and Experiences of Key Stakeholders." Patient Preference and Adherence 17: 2971-2980.
	Background: Historically, menopausal symptoms have been hugely under-treated and under-reported, with many women struggling to manage intrusive, bothersome symptoms which can significantly affect quality of life. In the past couple of years, awareness of the impact of the menopause has risen in the public health agenda but many women are still not receiving adequate information and support. Aim(s): To gain an in-depth understanding of the barriers that impact women's access to treatment and uptake of hormone replacement therapy (HRT). Design and Setting: Qualitative study with perimenopausal and menopausal women, general practitioners (GPs) and gynaecologists in the UK. Method(s): Sixty-minute in-depth interviews conducted with 20 menopausal women, 30 GPs and 10 gynaecologists. Data from the interviews were analysed thematically. Result(s): Barriers to seeking help for menopausal symptoms include: a lack of knowledge of the full range of symptoms, stigma, embarrassment and the belief that it is part of normal ageing. Previous negative experience in accessing advice or treatment discouraged women from pursuing help. There are substantial differences in the beliefs and attitudes towards the menopause amongst GPs and often a lack of confidence in prescribing HRT. Secondary care services can consequently be overwhelmed by an explosion in uncomplicated referrals which could be effectively managed in primary care. Conclusion(s): There are barriers at each point in the management pathway: from women not feeling empowered to seek medical advice, to some women feeling their symptoms are dismissed by healthcare professionals (HCP); or HCPs not recognising some of the less common menopausal symptoms, not offering options for treatment, both hormonal and non-hormonal, or offering onward specialist referral for complex issues outside their expertise. There are multiple opportunities to address these gaps in knowledge, including the use of HCP education and culturally appropriate leaflets to reach a wider range of perimenopausal and menopausal women.Copyright © 2023 Barber and Charles.

Barbier, H., et al. (2023). "International Urogynecology consultation chapter 2 committee 3: the clinical evaluation of pelvic organ prolapse including investigations into associated morbidity/pelvic floor dysfunction." International Urogynecology Journal 34(11): 2657-2688.
	Introduction and Hypothesis: This manuscript from Chapter 2 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) reviews the literature involving the clinical evaluation of a patient with POP and associated bladder and bowel dysfunction.; Methods: An international group of 11 clinicians performed a search of the literature using pre-specified search MESH terms in PubMed and Embase databases (January 2000 to August 2020). Publications were eliminated if not relevant to the clinical evaluation of patients or did not include clear definitions of POP. The titles and abstracts were reviewed using the Covidence database to determine whether they met the inclusion criteria. The manuscripts were reviewed for suitability using the Specialist Unit for Review Evidence checklists. The data from full-text manuscripts were extracted and then reviewed.; Results: The search strategy found 11,242 abstracts, of which 220 articles were used to inform this narrative review. The main themes of this manuscript were the clinical examination, and the evaluation of comorbid conditions including the urinary tract (LUTS), gastrointestinal tract (GIT), pain, and sexual function. The physical examination of patients with pelvic organ prolapse (POP) should include a reproducible method of describing and quantifying the degree of POP and only the Pelvic Organ Quantification (POP-Q) system or the Simplified Pelvic Organ Prolapse Quantification (S-POP) system have enough reproducibility to be recommended. POP examination should be done with an empty bladder and patients can be supine but should be upright if the prolapse cannot be reproduced. No other parameters of the examination aid in describing and quantifying POP. Post-void residual urine volume >100 ml is commonly used to assess for voiding difficulty. Prolapse reduction can be used to predict the possibility of postoperative persistence of voiding difficulty. There is no benefit of urodynamic testing for assessment of detrusor overactivity as it does not change the management. In women with POP and stress urinary incontinence (SUI), the cough stress test should be performed with a bladder volume of at least 200 ml and with the prolapse reduced either with a speculum or by a pessary. The urodynamic assessment only changes management when SUI and voiding dysfunction co-exist. Demonstration of preoperative occult SUI has a positive predictive value for de novo SUI of 40% but most useful is its absence, which has a negative predictive value of 91%. The routine addition of radiographic or physiological testing of the GIT currently has no additional value for a physical examination. In subjects with GIT symptoms further radiological but not physiological testing appears to aid in diagnosing enteroceles, sigmoidoceles, and intussusception, but there are no data on how this affects outcomes. There were no articles in the search on the evaluation of the co-morbid conditions of pain or sexual dysfunction in women with POP.; Conclusions: The clinical pelvic examination remains the central tool for evaluation of POP and a system such as the POP-Q or S-POP should be used to describe and quantify. The value of investigation for urinary tract dysfunction was discussed and findings presented. The routine addition of GI radiographic or physiological testing is currently not recommended. There are no data on the role of the routine assessment of pain or sexual function, and this area needs more study. Imaging studies alone cannot replace clinical examination for the assessment of POP. (© 2023. The Author(s).)

Barbosa, C., et al. (2023). "Mapping acceptance and commitment therapy outcomes in the context of infertility: A systematic review." Current Psychology: A Journal for Diverse Perspectives on Diverse Psychological Issues: No-Specified.
	Evidence suggests that individuals with infertility are confronted with psychosocial challenges. This has led to a significant number of studies highlighting the subsequent negative effects on mental health. Acceptance and Commitment Therapy (ACT) has already been established as having a beneficial effect on psychological issues related to other health conditions. Since infertility is a relevant stressor, ACT was also expected to have a protective effect on the mental health of individuals with this disease. A systematic review of the literature was conducted to identify studies assessing Infertility and ACT. Empirical and quantitative studies were considered when they assessed mental health variables and ACT hexagon model components in patients with infertility. Out of the 137 studies initially identified, six met the eligibility criteria and were included in the review. The samples were composed of women (three) and couples (three). Since ACT variables appear to be associated with better mental health outcomes, couples with infertility were expected to benefit from intervention addressing ACT components. Implications for future research include the need for a distinction between ACT variables, the use of validated assessment methods and the empirical examination of predictors of changes in ACT variables. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Barbosa Marina, Z., et al. (2019). "Three-dimensionally-printed models in reproductive surgery: systematic review and clinical applications." Minerva ginecologica 71(3): 235-244.
	Introduction: 3D printing has wide application in medicine while it provides customizability and precision for anatomical model development. Our aims were to perform a systematic review and to explore the use of 3D printing applications on human reproduction and reproductive surgery.; Evidence Acquisition: We have performed a systematic review in PubMed database to assess previous publications within 3D printing in human reproduction and gynecology. We have developed 3D models according to patients' magnetic resonance images (MRI). MRI were transformed into DICOM images that originated our 3D virtual models and PolyJet technology was applied for the printing process. We included two infertile patients in reproductive age with surgical indication for hysteroscopy septoplasty and myomectomy.; Evidence Synthesis: Of 1965 studies searched, we excluded 1934 publications based on their titles. Abstracts of 31 remained studies were read, and 24 studies were selected for full-text analysis. We included 11 studies for the systematic review, based on our eligibility criteria. We have designed four 3D models (uterus, ovaries, uterine cervix and uterus with fibroids) that provided enriched information to improve pre-surgical planning, medical training, fertility-sparing surgery, patient comprehension of surgical procedures and assisted reproduction applications.; Conclusions: 3D models for human reproduction are feasible. They might improve assisted reproductive techniques, help in pre-surgical planning for reproductive surgeries, and provide accurate measures of ovarian reserve. Besides, we see future applications in endometrioma research and in the fabrication of devices, such as embryo transfer catheter and a 3D printed embryo.

Barbosa Pâmela Maria, M., et al. (2023). "Parameters and results of non-invasive neuromodulation in the management of chronic pelvic pain: integrative literature review." BrJP 6(3): 313-319.
	ABSTRACT BACKGROUND AND OBJECTIVES: Chronic Pelvic Pain (CPP) is characterized by persistent pain in the pelvic region for more than six months, affecting both men and women and causing significant impairment in quality of life (QoL). Two of the main non-invasive approaches are Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). These techniques aim to modulate neural activity and promote pain relief. In this context, this research conducted an integrative literature review to summarize the results of relevant studies, aiming to identify the key parameters used in TMS and tDCS for CPP treatment. The objective was to assess the effect and efficacy of non-invasive neuromodulation as a therapeutic intervention for CPP. CONTENTS: For this integrative review, electronic searches were conducted in Pubmed, Scielo, PEDro, Medline, Cochrane, and Scopus databases, examining studies in Portuguese, English, or Spanish. The keywords "pelvic pain," "transcranial direct current stimulation," and "transcranial magnetic stimulation" and their derivatives were searched in the three languages in studies from 2013 to 2023. Seven studies were included for analysis. Both techniques showed positive effects in managing CPP, improving pain levels and quality of life to a relevant extent. However, there is still no consensus on the parameters applied in TMS and tDCS techniques for CPP. CONCLUSION: Non-invasive neuromodulation improves pain levels and quality of life in patients with CPP. Further studies are needed to establish more reliable parameter relationships, and the limited number of studies restricts definitive conclusions on the subject.

Barbounaki, S. G., et al. (2021). "Fuzzy logic intelligent systems and methods in midwifery and obstetrics." Acta Informatica Medica 29(3): 210-215.
	Background: Fuzzy logic can be used to model and manipulate imprecise and subjective knowledge imitating the human reasoning. Objective(s): The aim of this systematic review was to analyze research studies pertaining to fuzzy logic and fuzzy intelligent systems applications in midwifery and obstetrics. Method(s): A thorough literature review was performed in four electronic databases (PubMed, APA PsycINFO, SCOPUS, ScienceDirect). Only the papers that discussed fuzzy logic and fuzzy intelligent systems applications in midwifery and obstetrics were considered in this review. Selected papers were critically evaluated as for their relevance and a contextual synthesis was conducted. Result(s): Twentynine papers were included in this systematic review as they met the inclusion and methodological criteria specified in this study. The results suggest that fuzzy logic and fuzzy intelligent systems have been successfully applied in midwifery and obstetrics topics, such as diagnosis, pregnancy risk assessment, fetal monitoring, bladder tumor, etc. Conclusion(s): This systematic review suggests that fuzzy logic is applicable to midwifery and obstetrics domains providing the means for developing affective intelligent systems that can assist human experts in dealing with complex diagnosis and problem solving. However, its full potential is not yet been examined, thus presenting an opportunity for further research.Copyright © 2021 Stavroula G Barbounaki, Antigoni Sarantaki, Kleanthi Gourounti

Barboza Josianne, R., et al. (2023). "Molecular mechanisms of action and chemosensitization of tumor cells in ovarian cancer by phytochemicals: A narrative review on pre-clinical and clinical studies." Phytotherapy research : PTR 37(6): 2484-2512.
	Ovarian cancer is the second-leading cause of death among women with cancer of the genital tract. Currently, drugs derived from platinum and taxanes constitute the majority of ovarian cancer treatments. Patients undergoing this chemotherapy are susceptible to cumulative toxic effects and resistance to chemotherapy. Therefore, it is crucial to identify treatment options that are both more effective and better tolerated by patients. Phytochemicals in this context are plant-derived chemicals with antitumor activity that can be used as therapeutic or adjuvant agents in the treatment of ovarian cancer. Consequently, the purpose of this literature review is to demonstrate through existing pre-clinical and clinical trials the potential of phytochemicals in the treatment of ovarian cancer, the mechanisms of action involved, and to contribute to the development of new therapeutic options for ovarian cancer. For this review, the databases PubMed, Scopus, Science Direct, and ClinicalTrials.gov were queried between 2010 and 2022 using terms such as "ovarian cancer," "phytochemicals," "phenolic compounds," "terpenes," and "alkaloids." The present review summarized the possible molecular mechanisms of action by which phytochemicals, such as phenolic acids, flavonoids, diterpenes, triterpenes, saponins, and alkaloids, inhibit this type of cancer, specifically the ability of phytochemicals to induce cell growth regulation, apoptosis, oxidative stress reduction, anti-angiogenesis, and chemosensitization of tumors in ovarian cancer. As their action and cellular mechanism have already been demonstrated in several pre-clinical trials, the phytochemicals identified in our study have the potential to be investigated for the treatment of ovarian cancer. Through pre-clinical and clinical trials, our study demonstrates the potential of phytochemicals in the treatment of ovarian cancer, contributing to the development of novel therapeutic options for ovarian cancer. (© 2023 John Wiley & Sons Ltd.)

Barcellini, A., et al. (2022). "Sexual Health Dysfunction After Radiotherapy for Gynecological Cancer: Role of Physical Rehabilitation Including Pelvic Floor Muscle Training." Frontiers in Medicine 8: 813352.
	Introduction: The present study aims to describe: 1. How the side effects of radiotherapy (RT) could impact sexual health in women; 2. The effectiveness of physical rehabilitation including pelvic floor muscle training (PFMT) in the management of sexual dysfunction after RT.; Materials and Methods: Search keys on PubMed, Web of Science, Scopus, PEDro, and Cochrane were used to identify studies on women treated with radical or adjuvant RT and/or brachytherapy for gynecological cancers with an emphasis on vulvo-vaginal toxicities and PFMT studies on sexual dysfunction for this group of women.; Results: Regarding the first key question, we analyzed 19 studies including a total of 2,739 women who reported vaginal dryness, stenosis, and pain as the most common side effects. Reports of dosimetric risk factors and dose-effect data for vaginal and vulvar post-RT toxicities are scant. Only five studies, including three randomized controlled trials (RCTs), were found to report the effect of PFMT alone or in combination with other treatments. The results showed some evidence for the effect of training modalities including PFMT, but to date, there is insufficient evidence from high-quality studies to draw any conclusion of a possible effect.; Conclusions: Gynecological toxicities after RT are common, and their management is challenging. The few data available for a rehabilitative approach on post-actinic vulvo-vaginal side effects are encouraging. Large and well-designed RCTs with the long-term follow-up that investigate the effect of PFMT on vulvo-vaginal tissues and pelvic floor muscle function are needed to provide further guidance for clinical management.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Barcellini, Dominoni, Dal Mas, Biancuzzi, Venturini, Gardella, Orlandi and Bø.)

Barcellini, A., et al. (2023). "Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group." Critical Reviews in Oncology/Hematology 193: 104201.
	Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

Barcellini, A., et al. (2023). "Granulosa cell tumors (GCTs) of the ovary: What is the role of radiotherapy?" Critical Reviews in Oncology/Hematology 181: 103889.
	Granulosa cell tumors of the ovary have an indolent behavior and a good prognosis, but a high incidence of local recurrence after surgery. The best treatment in the recurrent setting is unclear and randomized clinical trials on the management in the recurrent setting are lacking. The role of radiotherapy is controversial in adjuvant settings and unknown in case of relapse after surgery. This review aims to summarize the level of evidence of the role of radiation treatments for granulosa cell tumors of the ovary.; Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Barcelona Hospital Clinic, o. (2021). Effects of Ospemifene on Brain Activation Patterns in Women With Sexual Interest-arousal Disorders.
	To evaluate changes from baseline in brain activation patterns, by using functional magnetic resonance imaging (fMRI) techniques and sexual stimuli, in postmenopausal women with moderate to severe vulvovaginal atrophy and FSIAD after 3 months treatment with ospemifene 60mg/day compared to those treated with placebo. fMRI technique allows the study of brain activation by detecting brain blood flow and oxygen level dependent changes induced by neuronal activation.

Barcelona Hospital Clinic, o. and d. Octubre Hospital Universitario (2024). A Multimodal Intervention Program to Improve Sexual Health and Self-perceived Quality of Life in Patients Treated for Cervical Cancer (PROVIDENCE).
	No Results Available Combination Product: Multimodal intervention on sexual dysfunction and quality-of-life FSFI score|FSFI (6 months)|EORTC QLQ-30|EORTC QLQ-30 (6 months)|EORTC Cx-24 (6 months)|EORTC Cx-24 Female Phase 4 122 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment PROVIDENCE April 2025

Barcikowska, Z., et al. (2022). "Effect of Manual Therapy Compared to Ibuprofen on Primary Dysmenorrhea in Young Women-Concentration Assessment of C-Reactive Protein, Vascular Endothelial Growth Factor, Prostaglandins and Sex Hormones." Journal of Clinical Medicine 11(10).
	Background: The study aimed to assess if manual therapy, compared to ibuprofen, impacts the concentration of inflammatory factors, sex hormones, and dysmenorrhea in young women Methods: Thirty-five women, clinically diagnosed with dysmenorrhea, were included in the study. They were divided into group A-manual therapy ( n = 20) and group B-ibuprofen therapy ( n = 15). Inflammatory factors such as vascular endothelial growth factor (VEGF), C-reactive protein (CRP), prostaglandin F2α (PGF 2α ), E2 (PGE2) and sex hormones levels were measured. Dysmenorrhea assessed with the numerical pain rating scale (NPRS), myofascial trigger points, and muscle flexibility were examined before and after the interventions.; Results: The difference in the level of 17-β-estradiol after manual and ibuprofen therapy was significant, as compared to baseline ( p = 0.036). Progesterone levels decreased in group A ( p = 0.002) and B ( p = 0.028). The level of CRP was negatively correlated with sex hormones. Decrease in dysmenorrhea was significant in both groups (group A p = 0.016, group B p = 0.028). Non-significant differences were reported in prostaglandins, VEGF and CRP levels, in both groups.; Conclusions: There were no significant differences in CRP, prostaglandins and VEGF factors after manual or ibuprofen therapy. It has been shown that both manual therapy and ibuprofen can decrease progesterone levels. Manual therapy had a similar effect on the severity of dysmenorrhea as ibuprofen, but after manual therapy, unlike after ibuprofen, less muscles with dysfunction were detected in patients with primary dysmenorrhea.

Barcroft Jennifer, F., et al. (2021). "Fertility treatment and cancers-the eternal conundrum: a systematic review and meta-analysis." Human reproduction (Oxford, England) 36(4): 1093-1107.
	Study Question: Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer?; Summary Answer: Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer.; What Is Known Already: Infertility affects more than 14% of couples. Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious.; Study Design, Size, Duration: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337).; Participants/materials, Setting, Methods: In the final meta-analysis, 29 studies were included: breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so were included in each individual cancer meta-analysis. Primary outcome of interest was cancer incidence (breast, ovarian, endometrial and cervical) in FT and no-FT groups. Secondary outcome was cancer incidence according to specific fertility drug exposure. Odds ratio (OR) and random effects model were used to demonstrate treatment effect and calculate pooled treatment effect, respectively. A meta-regression and eight sub-group analyses were performed to assess the impact of the following variables, maternal age, infertility, study size, outliers and specific FT sub-types, on cancer incidence.; Main Results and the Role of Chance: Cervical cancer incidence was significantly lower in the FT group compared with the no-FT group: OR 0.68 (95% CI 0.46-0.99). The incidences of breast (OR 0.86; 95% CI 0.73-1.01) and endometrial (OR 1.28; 95% CI 0.92-1.79) cancers were not found to be significantly different between the FT and no-FT groups. Whilst overall ovarian cancer incidence was not significantly different between the FT and no-FT groups (OR 1.19; 95% CI 0.98-1.46), separate analysis of borderline ovarian tumours (BOT) revealed a significant association (OR 1.69; 95% CI 1.27-2.25). In further sub-group analyses, ovarian cancer incidence was shown to be significantly higher in the IVF (OR 1.32; 95% CI 1.03-1.69) and clomiphene citrate (CC) treatment group (OR 1.40; 95% CI 1.10-1.77), respectively when compared with the no-FT group. Conversely, the incidences of breast (OR 0.75; 95% CI 0.61-0.92) and cervical cancer (OR 0.58; 95% CI 0.38-0.89) were significantly lower in the IVF treatment sub-group compared to the no-FT group.; Limitations, Reasons for Caution: The large, varied dataset spanning a wide study period introduced significant clinical heterogeneity. Thus, results have to be interpreted with an element of caution. Exclusion of non-English citations, unpublished work and abstracts, in order to ensure data accuracy and reliability was maintained, may have introduced a degree of selection bias.; Wider Implications of the Findings: The results for breast, ovarian, endometrial and cervical cancer are reassuring, in line with previously published meta-analyses for individual cancers but the association between IVF and CC treatment and an increase in ovarian cancer incidence requires additional work to understand the potential mechanism driving this association. In particular, focusing on (i) discriminating specific treatments effects from an inherent risk of malignancy; (ii) differential risk profiles among specific patient sub-groups (refractory treatment and obesity); and (iii) understanding the impact of FT outcomes on cancer incidence.; Study Funding/competing Interest(s): This study did not receive any funding. The authors have no financial, personal, intellectual and professional conflicts of interest to declare.; Prospero Registration Number: CRD42019153404. (© Th Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Barczyński, B., et al. (2022). "Perspectives of metformin use in endometrial cancer and other gynaecological malignancies." Journal of drug targeting 30(4): 359-367.
	Insulin resistance and hyperinsulinemia play a key role in type 1 endometrial cancer pathogenesis. Most of these cancers develop on a background of overweight or type 2 diabetes mellitus (T2DM). One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways. Many epidemiological studies on diabetic patients show potential preventative role of metformin in endometrial cancer patients, but data regarding its therapeutic role is still limited. So far, most of attention has been paid to the concept of metformin use in fertility sparing treatment of early-stage cancer. Another investigated alternative is its application in patients with primary advanced or recurrent disease. In this review we present the latest data on clinical use of metformin in endometrial cancer patients and potential underlying mechanisms of its activity. Finally, we present some most important clinical information regarding metformin efficacy in other gynaecological malignancies, mainly breast and ovarian cancer.

Bardia, A., et al. (2021). "Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial." Annals of oncology : official journal of the European Society for Medical Oncology 32(6): 746-756.
	BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

Bardin Marcela, G., et al. (2023). "Does the addition of electrical stimulation or kinesiotherapy improve outcomes of amitriptyline treatment for women with vulvodynia? A randomized clinical trial." International Urogynecology Journal 34(6): 1293-1304.
	Introduction and Hypothesis: Women diagnosed with provoked vulvodynia frequently report a great deal of frustration in achieving symptomatic relief. Physical therapy and drug treatment are among the interventions most indicated by guidelines; however, whether those modalities are effective when combined remains unclear. The objective was to evaluate the effectiveness of adding a physical therapy modality compared with amitriptyline alone for the treatment of vulvodynia.; Methods: Eighty-six women with vulvodynia were randomized to (G1) 25 mg amitriptyline, once a day (n=27), (G2) amitriptyline + electrical stimulation therapy (n=29) or (G3) amitriptyline + kinesiotherapy (n=30). All treatment modalities were administered for 8 weeks. The primary endpoint was the reduction in vestibular pain. Secondary measurements focused on sexual pain, frequency of vaginal intercourse, Friedrich score, and overall sexual function. Data were analyzed using intention-to-treat.; Results: All treatment modalities resulted in a significant decrease in vestibular pain (p<0.001), sexual pain (p<0.05), Friedrich score (p<0.001), and an increase in the frequency of sexual intercourse (p<0.05). G3 was more effective than G1 at reducing sexual pain (G1: 5.3±3.3 vs G3: 3.2±2.7; p=0.01) and at improving sexual function (G1: 18.8±9.8 vs G3: 23.9±7.8; p=0.04).; Conclusion: Kinesiotherapy and electrotherapy additions to amitriptyline administration as well as amitriptyline alone, were effective at improving vestibular pain in women with vulvodynia. Women receiving physical therapy had the greatest improvement in sexual function and frequency of intercourse at post-treatment and follow-up. (© 2023. The International Urogynecological Association.)

Barel, O., et al. (2021). "Addition of Lidocaine to the Distension Medium in Hysteroscopy Decreases Pain during the Procedure-A Randomized Double-blind, Placebo-controlled Trial." Journal of Minimally Invasive Gynecology 28(4): 865‐871.
	STUDY OBJECTIVE: To evaluate the effect of adding a local anesthetic to the distension medium in office diagnostic hysteroscopy using the vaginoscopic approach on pain during the procedure. Secondary aims included documenting side effects, patient satisfaction, and the time needed to complete the procedure. DESIGN: Randomized double‐blind placebo‐controlled study. SETTING: University‐affiliated hospital; office hysteroscopy clinic. PATIENTS: Total of 100 patients who underwent office hysteroscopies divided in half with 50 in the intervention group and 50 in the control group. INTERVENTIONS: Ten mL of lidocaine 2% added to 1000 mL of saline solution that was used as the distension medium for hysteroscopy in the study group vs 1000 mL of saline alone in the control group. MEASUREMENTS AND MAIN RESULTS: A significant difference was found in the increment of pain as measured by visual analog scale after the hysteroscopy between the 2 groups. Patients receiving lidocaine had an average rise of 1.9 in the visual analog scale score after the procedure compared with 2.9 in the control group (p = .033). There was also a nonsignificant trend for shorter duration of hysteroscopy in the intervention group compared with the control group (180.1 vs 222.1 seconds, p = .08). Patients' satisfaction was high in both groups (98% for the study group and 92% for the control group). Success rates were also similar between the 2 groups at approximately 95%. No side effects were recorded in either group. CONCLUSION: The addition of local anesthetic to the distension medium in office hysteroscopy produces significant reduction in pain during the procedure without adding time to the procedure and without side effects.

Barfoot, K. L., et al. (2021). "Mental Health in New Mothers: A Randomised Controlled Study into the Effects of Dietary Flavonoids on Mood and Perceived Quality of Life." Nutrients 13(7).
	The postnatal period is a significant period of physical, physiological and psychological change for mothers, rendering them particularly vulnerable to changes in mood or disorders such as postnatal depression (PND). Previous interventions with foods high in flavonoids have demonstrated beneficial acute and chronic mood effects in healthy child, adolescent and adult populations. It is unclear whether mood effects persist in populations who are potentially at-risk of developing mood disorders, such as postnatal mothers. This exploratory study investigated the effects of a 2-week daily dietary flavonoid intervention on mood (PANAS-NOW), anxiety (STAI), depressive symptoms (PHQ-8) and perceived quality of life (WHOQOL-BREF) in forty-one new mothers in the 0-12-month postnatal period, before and after flavonoid intervention. Mothers either added high flavonoid foods to their daily diet, or did not include additions following a randomised, between-groups, controlled design. Significant effects were observed in the flavonoid group with mothers reporting lower state anxiety and higher perceived quality of physical health at the 2-week timepoint. These findings suggest that regular dietary consumption of flavonoids may benefit mothers' anxiety and perceived quality of life in the postnatal period. Replication of these results may indicate the potential for dietary flavonoids to promote healthy mood regulation in mothers or prevent the onset or severity of symptoms in postnatal psychological disorders, both of which would be beneficial for women's health services and public mental health.

Barinov, S. V., et al. (2021). "The use of an osmotic dilator for induction of miscarriage in patients with the second trimester missed miscarriage." Journal of maternal-fetal & neonatal medicine 34(17): 2778‐2782.
	Aim: The aim of this study was to assess the outcomes of combined use of dilapan‐S and pharmacological induction of miscarriage with mifepristone and misoprostol versus mifepristone and misoprostol only in patients with a second‐trimester pregnancy loss. Materials and methods: Our study included 74 patients with a second‐trimester antenatal death who were randomized into two groups to receive pharmacological induction of miscarriage combined with intracervical insertion of dilapan‐S (n = 37) or pharmacological induction of miscarriage only (n = 37). Efficacy endpoints included: blood loss volume, length of time between the procedure initiation and complete miscarriage, and the number of complications. Results: The use of dilapan‐S together with mifepristone and misoprostol for induction of miscarriage in the second trimester in women with antenatal fetal death reduced the time from the start of the procedure to complete miscarriage by 1.98‐fold. However, the use of dilapan‐S did not significantly reduce the odds of such post‐procedural complications as hematometra and retention of the products of conception in the uterus (p = .2501). Conclusions: Combined management of antenatal pregnancy loss in the second trimester including intracervical insertion of dilapan‐S and conventional induction with miscarriage may be considered a valuable clinical strategy. However, future studies should focus on ways to prevent postprocedural complications in this group of women.

Barlin, J., et al. (2023). "Lunchbox trial: a randomized phase III trial of Cisplatin and irradiation followed by Carboplatin and Paclitaxel vs. sandwich therapy of Carboplatin and Paclitaxel followed by irradiation then Carboplatin and Paclitaxel for advanced endometrial carcinoma (168)."  176: S63‐S64.
	Objectives: Advanced endometrial cancer comprises a heterogeneous group of patients whose survival generally remains poor. The optimal adjuvant treatment strategy for these patients is still not well defined. The objective of this study was to provide a real‐world evidence‐based answer to the most appropriate sequencing of combined modality treatment for advanced endometrial carcinoma. Methods: In this multicenter prospective study, patients were eligible if they had either FIGO 2009 surgical stage III or IVA endometrial carcinoma or stage I or II serous or clear cell endometrial carcinoma and positive cytology. Patients were randomized to receive cisplatin 50 mg/m2 IV days 1 and 29 plus volume‐directed radiation therapy followed by carboplatin AUC 5 or 6 plus paclitaxel 175 mg/m2 q 21 days for 4 cycles (ChemoRT then Chemo) versus carboplatin AUC 6 plus paclitaxel 175 mg/m2 q 21 days for 3 cycles followed by volume‐directed radiation therapy followed by carboplatin AUC 5 or 6 plus paclitaxel 175 mg/m2 q 21 days for 3 cycles (Sandwich Therapy). A futility analysis was planned. The primary objective was to determine if treatment with ChemoRT then Chemo improves progression‐free survival (PFS) when compared to Sandwich Therapy. The secondary objective was to evaluate overall survival (OS), whereas the tertiary objective was to compare the regimens with respect to tolerability and adverse effects of therapy. Patient characteristics of the two treatment groups were compared via Fisher's exact test, and Wilcoxon rank sum test as appropriate. PFS and OS of the two groups were described using Kaplan‐Meier survival curves and compared via Log‐rank test for equality of survivor functions. Statistical software STATA 16.0 was used for analysis. Results: This investigator‐initiated study was opened at 8 sites throughout the United States and Canada. Of the 48 patients enrolled, 42 patients were eligible for futility analysis, and the trial was closed early. The median follow‐up period was 30.9 months. Twenty‐two patients were randomized to ChemoRT then Chemo, and 20 patients were randomized to Sandwich Therapy. The 3‐year PFS was 85.7% (95% CI: 62–95) in the ChemoRT then Chemo arm and 73.4% (95% CI: 43–89) in the Sandwich Therapy group (P = 0.58). The 3‐year OS was 88.4% (95% CI: 61–97) in the ChemoRT then Chemo arm, and 80.9% (95% CI: 51–93) in the Sandwich Therapy group (P = 0.55). Ninety percent of patients were Caucasian, with a mean age of 61.7 and a BMI of 34.6. Ninety percent were in stage III at diagnosis, and 76.2% had endometrioid histology. Adverse events were similar between groups. All patients in the ChemoRT then Chemo group completed all cycles of chemotherapy. Ten percent of patients in the Sandwich Therapy arm were unable to complete their chemotherapy. Conclusions: The trial was limited by small numbers. After futility analysis, there was no difference observed between ChemoRT then Chemo and Sandwich Therapy in terms of progression‐free survival, overall survival, or adverse events. [Formula presented]

Barnard, N. D., et al. (2021). "The Women's Study for the Alleviation of Vasomotor Symptoms (WAVS): a randomized, controlled trial of a plant-based diet and whole soybeans for postmenopausal women." Menopause (New York, N.Y.) 28(10): 1150-1156.
	OBJECTIVE: This study aimed to assess the effects of the combination of a low-fat plant-based diet and soybeans on the frequency and severity of menopausal hot flashes. METHODS: Postmenopausal women (n = 38) reporting two or more hot flashes/day were randomly assigned to a low-fat, vegan diet, including ½ cup (86 g) of cooked soybeans daily, or to no diet changes for 12 weeks. Frequency and severity of hot flashes were recorded using a mobile application, and vasomotor, psychosocial, physical, and sexual symptoms were assessed using the Menopause-Specific Quality of Life Questionnaire. Significance was assessed using t-tests (continuous outcomes) and chi-squared/McNemar tests (binary outcomes). RESULTS: Total hot flashes decreased 79% in the intervention group (P < 0.001) and 49% in the control group (P = 0.002; between-group P = 0.01). Moderate-to-severe hot flashes decreased 84% in the intervention group (P < 0.001) and 42% in the control group P = 0.009; between-group P = 0.01). From 0 to 12 weeks, 59% (10/17) of intervention-group participants reported becoming free of moderate and severe hot flashes (P = 0.002). There was no change in this variable in the control group (between-group P < 0.001). The Menopause-Specific Quality of Life Questionnaire revealed significantly greater reductions in the intervention group in vasomotor (P < 0.0001), psychosocial (P = 0.04), physical (P < 0.002), and sexual (P = 0.01) domains. CONCLUSIONS: The combination of a low-fat, vegan diet and whole soybeans was associated with reduced frequency and severity of hot flashes and improved quality of life in vasomotor, psychosocial, physical, and sexual domains in postmenopausal women. During the 12-week study period, the majority of intervention-group participants became free of moderate-to-severe hot flashes.

Barnes, H. C., et al. (2022). "Using clinical estimate or catheter measurement of urethral mid-point result in similar retropubic mid-urethral sling position: a randomized trial." International Urogynecology Journal 33(12): 3555-3561.
	Introduction and hypothesis: The objective was to determine whether standardized, intraoperative urethral measurement improves retropubic mid-urethral sling (RPMUS) positioning and if the intraoperative position remains stable at 2 weeks postoperatively. Method(s): Participants undergoing a RPMUS were randomized to mid-urethral placement as per usual surgical care (no Foley catheter measurement, no-FCM) vs urethral mid-point Foley catheter measurement (FCM). The primary outcomes were RPMUS location as determined by 2D and 3D ultrasound 2 weeks postoperatively (as percentage from urethral meatus - relative to the urethral length) and intraoperatively following the RPMUS placement. Result(s): Forty-four women enrolled, underwent RPMUS, and provided baseline data and intraoperative ultrasound measurements; of these, 36 (82%) had interpretable intraoperative and postoperative ultrasound measurements. Demographic data were similar in the two groups. The mean RPMUS mid-point was 57 % and 55 % in measured and controls (p = 0.685); this same measurement was relatively unchanged at 2 weeks postoperatively at 57% and 54% respectively (p = 0.538). Very much and much improvement was reported on the PGI-I by 84% and 85% of participants in the FCM and no-FCM groups respectively. Conclusion(s): Intraoperative RPMUS position at 2 weeks after surgery is similar to the intraoperative position. Compared with usual surgical care, intraoperative measurement of urethral mid-point with a Foley catheter did not affect RPMUS sling position.Copyright © 2022, The International Urogynecological Association.

Barnes Kylie, N., et al. (2023). "Zuranolone: The First FDA-Approved Oral Treatment Option for Postpartum Depression." The Annals of Pharmacotherapy: 10600280231204953.
	Objective: The objective of this study was to review the characteristics, efficacy, and safety of zuranolone in the management of postpartum depression (PPD).; Data Sources: Literature was identified using PubMed (1966-August 2023) and EMBASE (1973-August 2023) and clinicaltrials.gov. Search terms included zuranolone, SAGE-217, and PPD with further limitation of those published in English.; Study Selection and Data Extraction: Articles selected for inclusion included trials evaluating zuranolone for the treatment of PPD.; Data Synthesis: Zuranolone was evaluated for the treatment of moderate to severe PPD in 2 phase III trials. Both studies resulted in statistically significant improvement in depressive symptoms at day 15 ( P = 0.003 and P < 0.001). Sustained differences in remission rates favoring zuranolone were found in both studies at day 45 compared with placebo ( P = 0.01 and P < 0.05). Zuranolone was well tolerated, with somnolence, dizziness, headache, and sedation reported as the most common side effects.; Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Zuranolone is only the second medication approved by the Food and Drug Administration (FDA) for PPD and offers an advantage over brexanolone in that it can administered orally in the outpatient setting. The rapid onset of effect of zuranolone is advantageous to traditional antidepressant therapy which can be weeks to months; however, limited information is available on safety during lactation.; Conclusions: The recent FDA approval of oral zuranolone for PPD offers a second rapid-acting treatment for PPD, extending the opportunity for treatment to patients in the outpatient setting.; Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Barnes Kylie, N., et al. (2023). "Ibrexafungerp in the Treatment of Vulvovaginal Candidiasis." The Annals of Pharmacotherapy 57(1): 99-106.
	Objective: To review the pharmacology, efficacy, and safety of ibrexafungerp in the management of vulvovaginal candidiasis (VVC).; Data Sources: Literature was sought using PubMed (1966-February 2022) and EMBASE (1973-February 2022), and clinicaltrials.gov. Search terms included ibrexafungerp, SCY-078, and VVC.; Study Selection and Data Extraction: All studies including humans and published in English with data assessing the efficacy and safety of ibrexafungerp for the treatment of VVC were evaluated.; Data Synthesis: A phase 2 dose-finding study found ibrexafungerp had similar efficacy to fluconazole in the clinical cure of VVC (51.9% vs 58.3%, respectively). Two phase 3 clinical trials demonstrated ibrexafungerp had statistical superiority over placebo for clinical cure in moderate to severe VVC ( P < 0.001 and P = 0.023, respectively). The most frequently reported adverse reactions in the clinical trials were gastrointestinal-related symptoms. To date, data comparing efficacy of ibrexafungerp and topical imidazoles in the treatment of VVC are nonexistent.; Relevance to Patient Care and Clinical Practice: Topical imidazoles and oral fluconazole are effective for the treatment of uncomplicated VVC. Due to increased resistance, limited fluconazole coverage for non- Candida albicans species, and potential for significant drug interactions associated with fluconazole use, alternative treatments for VVC are needed. Ibrexafungerp is a new oral triterpenoid antifungal agent indicated for the treatment of VVC. Additional clinical trials are needed to evaluate long-term safety data as well as efficacy and safety in specialty populations.; Conclusion: Ibrexafungerp, a recently approved triterpenoid antifungal agent, is an effective and well-tolerated option for the treatment of VVC.

Barnhart, K. T., et al. (2021). "Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: the ACT or NOT Randomized Clinical Trial." JAMA 326(5): 390‐400.
	Importance: Women with an early nonviable pregnancy of unknown location are at high risk of ectopic pregnancy and its inherent morbidity and mortality. Successful and timely resolution of the gestation, while minimizing unscheduled interventions, are important priorities. Objective: To determine if active management is more effective in achieving pregnancy resolution than expectant management and whether the use of empirical methotrexate is noninferior to uterine evacuation followed by methotrexate if needed. Design, Setting, and Participants: This multicenter randomized clinical trial recruited 255 hemodynamically stable women with a diagnosed persisting pregnancy of unknown location between July 25, 2014, and June 4, 2019, in 12 medical centers in the United States (final follow up, August 19, 2019). Interventions: Eligible patients were randomized in a 1:1:1 ratio to expectant management (n = 86), active management with uterine evacuation followed by methotrexate if needed (n = 87), or active management with empirical methotrexate using a 2‐dose protocol (n = 82). Main Outcomes and Measures: The primary outcome was successful resolution of the pregnancy without change from initial strategy. The primary hypothesis tested for superiority of the active groups combined vs expectant management, and a secondary hypothesis tested for noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed using a noninferiority margin of ‐12%. Results: Among 255 patients who were randomized (median age, 31 years; interquartile range, 27‐36 years), 253 (99.2%) completed the trial. Ninety‐nine patients (39%) declined their randomized allocation (26.7% declined expectant management, 48.3% declined uterine evacuation, and 41.5% declined empirical methotrexate) and crossed over to a different group. Compared with patients randomized to receive expectant management (n = 86), women randomized to receive active management (n = 169) were significantly more likely to experience successful pregnancy resolution without change in their initial management strategy (51.5% vs 36.0%; difference, 15.4% [95% CI, 2.8% to 28.1%]; rate ratio, 1.43 [95% CI, 1.04 to 1.96]). Among active management strategies, empirical methotrexate was noninferior to uterine evacuation followed by methotrexate if needed with regard to successful pregnancy resolution without change in management strategy (54.9% vs 48.3%; difference, 6.6% [1‐sided 97.5% CI, ‐8.4% to ∞]). The most common adverse event was vaginal bleeding for all of the 3 management groups (44.2%‐52.9%). Conclusions and Relevance: Among patients with a persisting pregnancy of unknown location, patients randomized to receive active management, compared with those randomized to receive expectant management, more frequently achieved successful pregnancy resolution without change from the initial management strategy. The substantial crossover between groups should be considered when interpreting the results. Trial Registration: ClinicalTrials.gov Identifier: NCT02152696.

Baron, M., et al. (2022). "Management of post-operative urinary incontinence after midurethral sling explantation for pelvic or perineal pain." International Urogynecology Journal 33(4): 1001-1006.
	Introduction and Hypothesis: The objective was to report the management of post-operative urinary incontinence after midurethral sling (MUS) revision for chronic pelvic pain (CPP), and to report functional outcomes.; Methods: From November 2004 to February 2018, a total of 89 women who underwent removal or section of MUS for CPP, were enrolled. Patients were divided into the transobturator tape (TOT) group (50 patients) and the tension-free vaginal tape (TVT) group (37 patients); 2 patients had had both slings implanted. We report the rate of stress urinary incontinence (SUI) recurrence, the rate of de novo urge urinary incontinence (UUI), the need for subsequent SUI or UUI surgery, and functional outcomes (pain and continence).; Results: Median follow-up was 41.4 months [0.9-138.8]. SUI recurrence or de novo UUI occurred in 52 cases (58.4%): 19 (51.3%) patients in the TVT group, 31 (62%) in the TOT group, and both patients (100%) who underwent total removal of both slings. Among patients with SUI recurrence or de novo UUI, 39 (75%) had pain relief after sling removal. Seventeen patients (32.6%) refused any treatment, 14 (26.9%) were cured with conservative therapy, and 21 (40.3%) underwent SUI or UUI surgery. One patient had de novo pelvic pain after reoperation. The overall continence rate for all patients who underwent sling revision was 82% (73 out of 89) at the last follow-up.; Conclusion: After MUS revision for CPP, post-operative UI may occur in 58.4% of patients, of which, one-fourth may be managed with conservative measures only. Forty percent of them had redo surgery with a low risk of pain recurrence and a high rate of urinary continence. (© 2021. The International Urogynecological Association.)

Baroni, L., et al. (2020). "Vegetarian diets during pregnancy: effects on the mother's health. A systematic review." Food & Function.
	While interest in vegetarian nutrition has been steadily increasing, some aspects have not yet been consistently investigated. One topic requiring evidence-based confirmation is the adoption of a vegetarian diet during pregnancy and lactation. Maternal diet is not only correlated with the fetus's and infant's health, but appears relevant for that of the mother as well. Not only is an adequate delivery of nutrients to the fetus and infant mandatory, but the increased physiological needs of the maternal body require an adequate supply of nutrients and can represent harmful stress events that may lead to well-defined pathological conditions. In this review, we aim to systematically investigate state-of-the-art of vegetarian diets during pregnancy and lactation, focusing on maternal nutritional status and pregnancy outcomes. Data are scarce, often inconsistent and not homogeneous for many of the topics we considered, mainly because only a few studies have been performed in developed countries, whereas other studies have derived from developing countries, where vegetarianism can be a proxy indicator of malnutrition. For this reason, we did not find sufficient data to provide evidence-based information and recommendations. To date, the available literature does not clearly support a negative impact on the mother's health and pregnancy outcomes, but, analogously with the findings in the vegetarian adult population, an improvement in the quality of studies might facilitate finding more information on the possible positive impact of well-planned vegetarian diets during pregnancy and lactation. More epidemiological and interventional studies are warranted, in order to address the question as to whether vegetarian nutrition represents an advantage for the mother or poses nutritional issues that need further attention.

Barr, C. E., et al. (2021). "Weight loss during intrauterine progestin treatment for obesity-associated atypical hyperplasia and early-stage cancer of the endometrium." Cancer Prevention Research 14(11): 1041-1050.
	Intrauterine progestin is a treatment option for women with atypical hyperplasia or low-risk endometrial cancer who wish to preserve their fertility, or whose poor surgical fitness precludes safe hysterectomy. We hypothesized that in such women with obesity, weight loss during progestin treatment may improve oncological outcomes. We conducted a prospective nonrandomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment. Women with a body mass index (BMI) >= 35 kg/m2 were offered bariatric surgery; those who declined and those with a BMI of 30 to 34.9 kg/m2 were encouraged to lose weight by lowcalorie diet. We assessed uptake of bariatric surgery; weight lost during progestin treatment; and the impact of more than 10% total body weight loss on progestin treatment response at 12 months. 71 women [median age 58 years (interquartile range; IQR 35-65); mean BMI 48 kg/m2 (SD 9.3)] completed the study. Twenty-three women (32%) had bariatric surgery, on average 5 months (IQR 3-8) after progestin treatment commenced. Weight change during progestin treatment was -33.4 kg [95% confidence interval (CI) -42.1, -24.7] and -4.6 kg (95% CI -7.8, -1.4) in women receiving bariatric surgery and low-calorie diet, respectively (P < 0.001). Fortythree women (61%) responded to progestin, while 23 (32%) showed stabilized and 5 (7%) progressive disease. Response at 12 months was not predicted by age or baseline BMI, but women who lost more than 10% of their total body weight were more likely to respond to progestin than those who did not (adjusted odds ratio 3.95; 95% CI 1.3, 12.5; P = 0.02). Thus weight loss may improve oncological outcomes in women with obesity-associated endometrial neoplastic abnormalities treated with progestin.Copyright © 2021 The Authors.

Barra, F., et al. (2019). "Nintedanib for Advanced Epithelial Ovarian Cancer: A Change of Perspective? Summary of Evidence from a Systematic Review." Gynecologic and Obstetric Investigation 84(2): 107-117.
	Background/aims: Epithelial ovarian cancer (EOC) is the sixth most commonly diagnosed cancer among women. Results with available therapies are far from being satisfactory and, therefore, current research is focusing on new anticancer drugs to improve the clinical response of these patients. Nintedanib is an oral multiple tyrosine kinases inhibitor, which targets angiogenesis. Considering the current scenario, the aim of this systematic review is to highlight the prevailing knowledge about pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of Nintedanib for the treatment of advanced EOC.; Methods: We performed a systematic review of the literature, screening all available articles about the treatment of advanced EOC with Nintedanib, including phase I, II, and III trials.; Results: Although in early phase clinical trials, Nintedanib has demonstrated anticancer activity and tolerability as monotherapy or in combination with carboplatin and paclitaxel. In the phase III trial AGO-OVAR 12, it obtained a modest improvement in progression-free survival (PFS) as first-line combination therapy for patients with advanced EOC. Interestingly, a PFS increase was observed in patients with non-high progression risk or low tumor burden.; Conclusion: Despite the promising results, further studies are needed to evaluate Nintedanib efficacy in women affected by EOC. (© 2018 S. Karger AG, Basel.)

Barra, F., et al. (2020). "The potential role of elagolix for treating uterine bleeding associated to uterine myomas." Expert Opinion on Pharmacotherapy 21(12): 1419-1430.
	Introduction: Uterine myomas represents a widespread gynecological disease of women in reproductive age. Although surgery remains the first choice for treating most patients, in the last years, new medical approaches have been considered in order to ameliorate heavy menstrual bleeding (HMB) related to their presence. Elagolix is a second-generation gonadotropin-releasing hormone (GnRH) antagonist under investigation for the long-term treatment of uterine myomas. Areas covered: The aim of this drug evaluation is to give a complete overview of pharmacokinetic and pharmacodynamic data on elagolix for treating HMB related to uterine myomas and to report the results of the current clinical trials in this setting. Expert opinion: In two previous phase II studies, this drug succeeded in ameliorating blood loss and quality of life of patients affected by uterine myomas with a good safety profile. Three phase III trials (ELARIS UF-I, UF-II, and EXTEND) investigated the efficacy, tolerability, and safety of elagolix at 300 mg twice daily with add-back therapy. The primary endpoint, consisting in the reduction in HMB compared to placebo, was met in the majority of patients under treatment. Currently, elagolix is under investigation in two other ongoing multicenter phase III clinical studies.Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Barrenetxea, Z., et al. (2022). "Time to bust some myths about progesterone supplementation in the luteal phase. Role of the route of administration and usefulness (or uselessness) of plasma determination." Human Reproduction 37(Supplement 1): i514.
	Study question: Is it worth measuring plasma progesterone levels after FET? Is there any difference in results depending on the route of progesterone administration? Summary answer: The administration route of progesterone supplementation after FET entails different plasmatic levels (whose determination is useless) but without any correlation with ongoing pregnancy. What is known already: Embryonic aneuploidy is likely to be the major contributor to human implantation failure, but not all failures are due to embryonic defects. The need for progesterone supplementation in ART frozen-thawed cycles is well accepted. Several studies have demonstrated an increase in live birth rate with progesterone luteal support although there is a discussion on the association of Progesterone levels on day of embryo transfer and birth or pregnancy loss rates. Moreover, although the effect of route of administration of progesterone on serum levels and pregnancy rates have been thoroughly studied, there is no consensus on the optimal endometrial preparation protocol. Study design, size, duration: Prospective, randomized study performed during the 2020-21. A total of 201 genetically screened blastocyst (after PGT-A) transfers were performed after endometrial preparation, performed with exogenous estrogen administration followed by progesterone administration before embryo transfer (ET) . After embryo transfer, two different Progesterone regimens were randomly administered. Group I and Group II (see Participants) Participants/materials, setting, methods: Group I patients (n = 100): 800 mg of micronized Progesterone was administered vaginally (CyclogestVR 1-0-1). Group II patients (n = 101): vaginal administration of 400 mg of micronized progesterone was combined with the subcutaneous administration of 25 mg of Progesterone (Prolutex 25VR ) Plasmatic progesterone (PP) levels on day of B-HCG determination (pregnancy test) (10 days after ET) and ultrasound confirmation of pregnancy (3 weeks after ET) were determined. The relationship between progesterone levels and ongoing pregnancy rates was amalyzed. Main results and the role of chance: The rate of positive pregnancy test among the 201 FET was 71,64%. The overall ongoing pregnancy was 58,71%. PP on day of pregnancy test was 24,92+/-1,27 ng/ml (mean+/-SEM). The corresponding figures por positive (n=144) and negative (n=57) HCG were 27,65+/-1,09 and 20,33+/-2,13 respectively (t=2,68; p=0,008). The PP levels on day of HCG determination were 23,12+/-1,48 among ongoing pregnancies whereas the levels among non-evolutive gestations were 48,78+/-3,55 (t=7,19; p=0,000). PP levels were significantly higher among group II patients (combined treatment) both, on day of B-HCG determination (28,25+/-1,22 ng/ml) and on day of ultrasound confirmation of a gestational sac (33,61+/-2,39) than among group I patients (vaginal treatment) (15,12+/-1,60 and 19,77+/-1,50 ng/ml) (t=0651, p=0,000 and t=5,38, p=0,000 respectively). But these differences do not correlate with ongoing pregnancy rates: 59 out of 101 (58,42%) in group I patients and 59 out of 100 (59%) in group II patients. Limitations, reasons for caution: Even though only euploid embryos have been transferred, ee must be cautious when drawing conclusions from the present study taking into account the limited number of cases evaluated. Wider implications of the findings: Since only euploid embryos have been transferred in the present study, results in terms of successful ongoing pregnancies may be influenced by endometrial factors. Although the need of progesterone supplementation among frozen-thawed cycles is accepted, some debate exists on the route of administration and the need of progesterone serum determinations.

Barretina-Ginesta, M.-P., et al. (2022). "Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial." Therapeutic advances in medical oncology 14: 17588359221126149.
	Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo.; Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib ( n = 487) or placebo ( n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019).; Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd ( n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9-8.9] and 4.1 [95% CI, 2.2-5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5-8.6] and 3.5 [95% CI, 1.7-5.6] months, respectively) in the HRd and ITT populations.; Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure.; Trial Registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016.; Plain Language Summary: Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patients' quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA. Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses:● The first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life.● The second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects. Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib - they are known as homologous recombination deficiency (HRd) patients.● When information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo.● Using the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo. Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patients' quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib.; Competing Interests: Competing interests: MPBG reports receiving lecture fees, advisory board fees, and travel support from AstraZeneca, Clovis Oncology, GSK, Merck, PharmaMar, Roche, and Tesaro. BJM has received honoraria and lecture fees from Tesaro. BP has received institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Genentech/Roche, Merck, Mersana, Tesaro/GSK, Toray, I-Mab, Incyte, and Seagen; and advisory board compensation from Arquer, AstraZeneca, Eisai, Elevar, Lilly, Merck, Mersana, Tesaro/GSK, I-Mab, ImmunoGen, InxMed, Onconova Therapeutics, Seagen, and Toray. AAu reports receiving consulting fees from GSK. DMC reports personal fees from GSK; has received honoraria from Roche; has served as a consultant to AstraZeneca and Mateon Therapeutics; and has received research grants to her institution from Genentech. DL reports receiving advisory board fees from Amgen, AstraZeneca, Clovis Oncology, Genmab, and ImmunoGen; grant support, paid to her institution, and consulting fees from PharmaMar; and grant support, paid to her institution, and advisory board fees from Merck. EIB reports receiving consulting fees, lecture fees, and travel support from AstraZeneca, Clovis, GSK, Tesaro, Roche, Roche Diagnostics, Eisai, and Merck Sharp & Dohme; and grant support to their institution from Roche Diagnostics, Merck Sharp & Dohme, and Bayer. AR has received grant support, advisory fees, and travel support from PharmaMar and Roche; advisory fees and travel support from AstraZeneca and Tesaro/GSK; advisory fees from Clovis; and grant support from Eisai. RS is an employee of Open Health Evidence and Access, which received research funding from GSK for this study. NK was an employee of Open Health Evidence and Access at the time of the study. CH and DG are employees of GSK. TW is a former employee of GSK. DMO reports grants and personal fees from Clovis; has served on advisory boards for Agenus, AstraZeneca, Eisai, Genentech/Roche, ImmunoGen, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Merck, Mersana, Myriad, Novartis Pharmaceuticals, Novocure, Regeneron Pharmaceuticals, Seagen, Tarveda, and Tesaro/GSK; has served on steering committees for Amgen; has served as a consultant to AbbVie, Agenus, Ambry, AstraZeneca, Eisai, Genentech/Roche, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Novartis Pharmaceuticals, Novocure, Seagen, and Tesaro/GSK; and has received research support to his institution from AbbVie, Agenus, Ajinomoto, Amgen, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, Ergomed Clinical Research, Genentech/Roche, Genmab, GOG Foundation, ImmunoGen, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Ludwig Institute for Cancer Research, Merck, Mersana, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron Pharmaceuticals, Seagen, Serono, Stemcentrx, Tesaro/GSK, TRACON Pharmaceuticals, VentiRx, and Yale University. AGM reports receiving consulting fees from Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Immunogen, Mersana, Merck Sharp & Dohme, Oncoinvent, PharmaMar, Roche, SOTIO, and Takeda; ecture fees rom AstraZeneca, Clovis, GSK, Merck Sharp & Dohme, PharmaMar, and Roche; travel support from AstraZeneca, GSK, and PharmaMar; grant support to their institution from Roche Holding and Tesaro. SH, CA, SAL, NC, and AAm have no conflicts to disclose. (© The Author(s), 2022.)

Barrington, D., et al. (2022). "Pembrolizumab for persistent, recurrent, or metastatic cervical cancer: a cost-effectiveness analysis (025)." Gynecologic Oncology 166(Supplement 1): S19.
	Objectives: To determine the cost-effectiveness of pembrolizumab in patients with persistent, recurrent, or metastatic cervical cancer. Method(s): A decision analysis model was created to evaluate the cost-effectiveness of platinum-based chemotherapy plus bevacizumab and pembrolizumab (CBP) relative to chemotherapy plus pembrolizumab (CP) and chemotherapy plus bevacizumab (CB). Published data from KEYNOTE-826 was used to estimate quality-adjusted life-years (QALYs), and drug cost estimates were obtained using average wholesale prices. Incremental cost-effectiveness ratios (ICERs) were calculated to determine cost/QALY. The willingness to pay (WTP) threshold was set at $100,000 per QALY saved. Sensitivity analyses were performed on cost and effectiveness for regimens containing pembrolizumab. Result(s): The cost of treatment with CB and CP were $416 million (M) and $713 M, respectively. The cost of treatment with CBP was $1.51 billion (B). Relative to CB, the ICER for CP was $92,678. CBP was dominated. Sensitivity analyses were performed varying the efficacy of CP and CBP. If overall survival (OS) after treatment with CP was less than 23.4 months, the ICER would exceed the WTP. If the OS from CP was assumed to be 20.4 months (midway between control and experimental arms of KEYNOTE-826), the ICER would increase to $183,039. If OS for CBP improved to 38 months, this regimen would be cost-effective. If CP is eliminated from the model, CBP becomes cost-effective relative to CB if the cost of pembrolizumab decreases from $12,080 to $2,913 per cycle. Conclusion(s): CP is cost-effective relative to CB for persistent, recurrent, or metastatic cervical cancer. In the baseline model, CBP was dominated. The efficacy of CBP would need to far exceed CP in order to be cost-effective. The cost-effectiveness of pembrolizumab-containing regimens improves with a decrease in drug cost. A closer look at the comparative efficacy between CP and CBP is needed to help inform treatment decisions for patients with persistent, recurrent, or metastatic cervical cancer.Copyright © 2022 Elsevier Inc.

Barry Parul, N., et al. (2022). "Definitive chemoradiation or radiation therapy alone for the management of vulvar cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(3): 332-337.
	Vulvar cancer is rare, and unresectable disease provides a therapeutic conundrum. Although definitive surgery remains the mainstay for curative treatment of vulvar cancer, a minority of patients present with advanced disease for which surgical resection would be extraordinarily morbid. Pre-operative and definitive radiation with radiosensitizing systemic therapy allows such patients an opportunity for cure. In this review, we explore the origins of pre-operative radiation, current treatment standards for pre-operative and definitive chemoradiation, and future directions.; Competing Interests: Competing interests: SB: Elsevier pathway consultant; Xoft DSMBVarian employer. PNB: Elsevier pathway consultant. DCL: None. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Bartels Helena, C., et al. (2020). "Quality of life following minimally invasive hysterectomy compared to abdominal hysterectomy: A metanalysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 252: 206-212.
	Objective: The aim of this meta-analysis is to review quality of life (QoL) in patients who underwent simple minimally invasive (MIS) hysterectomy compared to abdominal hysterectomy (AH) for benign conditions or endometrial cancer.; Methods: A literature search was performed of electronic databases including Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase from study inception until December 2019. Search terms included "QoL", "minimally invasive surgery" "laparoscopic hysterectomy" "abdominal hysterectomy". The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95 % confidence intervals (95 % CI).; Results: A total of 4988 citations were reviewed; 9 studies comprising 3116 patients were selected for the analysis. Publications reporting QoL in patients undergoing simple MIS hysterectomy compared to AH were included. 9 studies reporting 3 different QoL assessment tools were included: EuroQoL five dimensions visual analogue scale (EQ-5D-VAS), Functional Assessment of Cancer Therapy-General (FACT-G) and Short Form-36 (SF-36). For EQ-5D, patients in the MIS group had a significantly higher QoL compared to those in the AH group at 1 week (OR 9.82, 95 % CI 4.61-15.03, p = 0.0002) and 4 weeks (OR 4.83 95 % CI 0.71-8.95, p = 0.02) post-operatively. Similarly, for FACT-G, at 1 week and at 4 weeks post operatively, patients in the MIS group reported a significantly higher score compared to those in the AH group (1 week: OR 6.39, 95 % CI 3.16-9.61, p = 0.0001, 4 weeks: OR 6.33, 95 % CI 3.55-9.12, p = <0.00001). There was no difference in SF-36 scores at any time point between the groups.; Conclusion: MIS hysterectomy is associated with improved QoL in the short term post-operative phase compared to AH both for benign disease and endometrial cancer.; Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare. (Copyright © 2020. Published by Elsevier B.V.)

Bartels Helena, C., et al. (2019). "A meta-analysis of morbidity and mortality in primary cytoreductive surgery compared to neoadjuvant chemotherapy in advanced ovarian malignancy." Gynecologic Oncology 154(3): 622-630.
	Aim The aim of this meta-analysis is to review the morbidity and mortality associated with primary cytoreductive surgery (PCS) compared to neoadjuvant chemotherapy and interval cytoreductive surgery (NACT + ICS) for advanced ovarian cancer.; Methods: A literature search was performed for publications reporting morbidity and mortality in patients undergoing PCS compared to NACT + ICS. Databases searched were Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase. Two independent reviewers applied inclusion and exclusion criteria to select included papers, with differences agreed by consensus. A total of 1341 citations were reviewed; 17 studies comprising 3759 patients were selected for the analysis. The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI).; Results: Patients in the PCS group were significantly more likely to have a Clavien-Dindo grade ≥ 3 morbidity with an overall rate of 21.2% compared to 8.8% (95%CI 1.9-4.0, p < 0.0001) and were more likely to die within 30 days of surgery (OR 6.1, 95% CI 2.1-17.6, p = 0.0008). Patients who underwent NACT + ICS had significantly shorter procedural times (MD -35 min, p = 0.01), lost less blood intraoperatively (MD-382 ml, p < 0.001) and had an average admission 5.0 days shorter (MD -5.0 days, 95% CI -8.1 to -1.9 days, p = 0.002) than those undergoing PCS. While NACT was associated with significantly increased optimal and complete cytoreduction rates (OR 1.9, 95% CI 1.3-2.9, p = 0.001, and OR 2.2, 95% CI 1.5-3.3, p = 0.0001 respectively), this did not confer any additional survival benefit (OR 1.0, p = 0.76).; Conclusion: NACT is associated with less morbidity and mortality and improved complete cytoreduction compared to PCS, with no survival benefit. Hence NACT is an acceptable alternative in selected patients in particular with medical co-morbidities or a high tumour burden. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Barthwal, M., et al. (2021). "Music Therapy to Alleviate Anxiety in Cervical Brachytherapy – Do We Change a Tune? A Randomized, Single Institute Study." International journal of radiation oncology biology physics 111(3): e610.
	Purpose/Objective(s): The procedure of Intracavitary Brachytherapy (ICBT) involves use of spinal anesthesia and invasive procedure leading to anxiety among the patients. Music therapy (MT) has been established as an excellent measure to alleviate anxiety; however, the role is scarcely employed. This randomized study evaluates the impact of MT on anxiety and distress during the procedure of ICBT in cervical malignancies. Materials/Methods: In this single institute, Randomized trial comparing MT versus no MT in patients undergoing ICBT for cervical malignancies, subjective assessment for stress and anxiety was done with use of pre‐State‐Trait Anxiety Inventory (STAI‐S Anxiety) questionnaire and Symptom Distress Thermometer (SDT). Patients under the MT group were counselled for their choice of music prior to the treatment and the non‐MT group did not receive any such counselling. After the completion of treatment, both the questionnaires were again repeated and repeated‐measures analysis of variance was used to assess treatment effects on STAI and SDT. Correlation between STAI and SDT was also assessed at both time points and by group with Spearman correlation coefficients. Results: A total of 70 patients with histopathological proven cervical malignancy were enrolled with 35 each in the MT and non‐MT group. The median age was 48.5 years and both groups were matched in the treatment and patient characteristics. The overall mean pre‐ and post‐simulation STAI‐S scores were 42.3 (range, 22‐62) and 37.7 (range, 20‐64), respectively. The overall mean pre‐ and post‐simulation SDT scores were 4.6 (range, 0‐10) and 3.2 (range, 0‐10), respectively. The MT group had mean pre‐ and post‐simulation STAI‐S scores of 42.8 and 32.3, respectively (P < 0.001) and the mean SDT scores before and after simulation were 4.5 and 1.9, respectively (P < 0.001) The no‐MT group's mean pre‐ and post‐simulation STAI‐S scores were 41.9 and 39.9, respectively (P = 0.54), and the mean SDT scores were 4.7 and 3.9, respectively (P = 0.76). Conclusion: The role of Music therapy as a method to reduce the patient anxiety has been well established in our study. The reduced anxiety in the patient helps the oncologist in performing a better implant which indirectly would lead to better disease control and survival. MT should be incorporated in the Brachytherapy Operating room to help alleviate the patients alleviate their procedure related stress and anxiety. Author Disclosure: M. Barthwal: None. V. Pareek: None. P.A. Patil: None. S. Mallick: None. A. Sharma: None. D. Sharma: None.

Bartiromo, L., et al. (2021). "Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review." Nutrients 13(8).
	The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.

Bartoletti, M., et al. (2020). "Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis." International Journal of Molecular Sciences 21(11).
	Introduction: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering BRCA genes status.; Methods: We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to BRCA genes status as follows: all comers (AC) population, BRCA 1/2 mutated (BRCAm), and BRCA wild type patients (BRCAwt).; Results: In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54-0.91). In the BRCA mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36-0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63-1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively).; Conclusions: PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.; Competing Interests: F.P. reports grants from AstraZeneca; grants, personal fees, and other from Roche; personal fees and other from Eli Lilly; personal fees from Amgen; personal fees from Ipsen; personal fees from MSD; personal fees from Takeda; grants and other from Eisai; other from Novartis and Pfizer, outside the submitted work. L.G. reports personal fees from Eli lilly, outside the submitted work. The other authors have nothing to disclose.

Barton Debra, L., et al. (2022). "Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 40(4): 324-334.
	Purpose: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities.; Methods: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t -tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t -test.; Results: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups.; Conclusion: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.; Competing Interests: Debra L. BartonResearch Funding: Merck Stephanie L. PughResearch Funding: Pfizer (Inst), Millennium (Inst) Patricia A. GanzLeadership: Intrinsic LifeSciences (I)Stock and Other Ownership Interests: Xenon Pharma (I), Intrinsic LifeSciences (I), Teva, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott LaboratoriesConsulting or Advisory Role: InformedDNA, Vifor Pharma (I), Ambys Medicines (I), Global Blood Therapeutics (I), GlaxoSmithKline (I), Ionis Pharmaceuticals (I), Protagonist Therapeutics (I), Akebia Therapeutics (I), Regeneron (I), Sierra Oncology (I), Rockwell Medical Technologies Inc (I), Astellas Pharma (I), Gossamer Bio (I), American Regent (I), Disc Medicine (I), Blue Note Therapeutics (I), Grail (I)Research Funding: Blue Note Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease, UpToDate royalties for section editor on survivorshipTravel, Accommodations, Expenses: Intrinsic LifeSciences (I) Steven C. PlaxeStock and Other Ownership Interests: Pfizer, Merck, Zimmer Biomet, GlaxoSmithKline, AstraZeneca, Bristol Myers Squibb/Pfizer, Johnson & Johnson/JanssenResearch Funding: Endocyte, Incyte, MedImmune, Novartis, Pfizer, Janssen Oncology, BIND Therapeutics, PharmaMar, AstraZeneca, Kevelt, Millennium, Tesaro Bridget F. KoontzEmployment: GenesisCareLeadership: GenesisCareConsulting or Advisory Role: Blue Earth Diagnostics, Myovant Sciences, Rythera TherapeuticsResearch Funding: Janssen, Merck, Blue Earth DiagnosticsPatents, Royalties, Other Intellectual Property: Demos Publishing Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava SciencesOpen Payments Link: https://openpaymentsdata.cms.gov/physician/820072 Carolyn Y. MullerResearch Funding: AstraZeneca, Genmab, VBL Therapeutics, Roche/Genentech, TapImmune Inc, Linnaeus Therapeutics, Agenus, Incyte, MerckPatents, Royalties, Other Intellectual Property: Have a pending patent on the cancer use for R-ketorolac—not yet its own new drugOther Relationship: NCI, Department of D fense Lisa A. KachnicConsulting or Advisory Role: New B InnovationResearch Funding: Varian Medical SystemsPatents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

Barts, et al. (2021). Virtual Reality in MVA for Miscarriage.
	No Results Available Device: Virtual reality Anxiety rating|Pain rating Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 271029 January 31, 2023

Baruch, Y., et al. (2023). "Pre- versus Post-Menopausal Onset of Overactive Bladder and the Response to Vaginal Estrogen Therapy: A Prospective Study." Medicina (Kaunas, Lithuania) 59(2).
	Background and Objectives: This study examined the utility of local estrogen therapy for improving urinary symptoms in women diagnosed with Overactive Bladder allied to the time of onset of urinary symptoms whether pre- or post-menopausal. Materials and Methods : Subject to informed consent, menopausal women diagnosed with Overactive Bladder (OAB) and Genitourinary Syndrome of Menopause (GSM) were enrolled at three urogynecological units. OAB symptoms were scored using the Global Pelvic Floor Symptoms Bother Questionnaire (GPFSBQ), with explicit attention to question number 3 that specifically addresses the presence or absence of urgency and the Patient Perception of Intensity of Urgency Scale (PPIUS). The Vaginal Health Index (VHI) was used to assess the vaginal mucosa trophism. Exclusion criteria included: Pelvic organ prolapse (POP) ≥ stage II, urinary tract infection or disease, diabetes, inflammatory diseases, use of diuretics, alcohol or drug addictions, neurological and/or psychiatric disorders, and other precluding conditions. Women were treated with local estrogens for 3 months and re-evaluated. Results : Forty-three post-menopausal women were enrolled. Of these, ten women developed OAB symptoms before menopause (Group I) and 33 developed symptoms after menopause (Group II). Following local estrogen therapy, based on the Global Pelvic Floor Symptoms Bother Questionnaire, improvement of OAB symptoms was reported by 20% of patients in Group I ( p = 0.414) and 64% of patients in Group II, ( p = 0.002). Based on the PPIUS scale, diminution in urinary urgency was experienced by 20% of patients in Group I ( p = 0.68) and 66% of patients in Group II ( p = 0.036). Improved VHI scores were graded statisticaly significant in both groups (Group I in 100% of women, p = 0.005 vs. 76% in Group II, p = 0.004). Conclusions : Our results indicate that local estrogen therapy is more effective in women who develop OAB after menopause.

Bashir, R., et al. (2022). "Insights into New Therapeutic Approaches for the Treatment and Management of Polycystic Ovary Syndrome: An Updated Review." Current Pharmaceutical Design 28(18): 1493-1500.
	Background: Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive-age women globally.; Objective: This review aims to facilitate an understanding of novel PCOS management approaches and highlight the results from relevant interventional animal and human studies.; Methods: Manual search on PubMed, Cochrane, and Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.; Results: According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulinsensitizing, and anti-obesity activities, along with the restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.; Conclusion: Exhaustive, multicentric and multiethnic studies are vital to generating a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data are warranted to corroborate the new therapeutics and direct health care resources accordingly. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Baskar, T., et al. (2022). "Interventions For Postpartum Depression: Systematic Review." NeuroQuantology 20(14): 1136-1146.
	Postpartum depression (PPD) is a common complication of childbearing, and has increasingly been identified as a major public health problem. Untreated maternal depression has multiple potential negative effects on maternal-infant attachment and child development. Despite available treatments for postpartum depression, numerous barriers hinder women to access care including time, financial constraints, and childcare concerns. Therefore therefore the interventions needs to be conifirmed for the effectiveness. The review aims to explore available interventions for the postpartum depression in Asia. The study involved a systematic review from internet databases such as Pubmed and CINHAL. Following that, databases were accessed to conduct a more detailed search of the literature using key phrases and Boolean operators to create articles pertinent to the issue. 1740 records identified. The duplicates andthose not matching with the criteria were excluded. 8 articles were filtered using aninclusion/exclusion criterion. Results showed overall the systematic reviews on interventions for PPD are of low-moderate quality and are not improving over time. Traditional Chinese herbal medicine was effective in the management of PPD and thus could provide a useful therapeutic alternative for women who prefer natural options over conventional therapies. The efficacy of physical exercise, and CBT for the treatment of PPD remain equivocal. Hypnosis in PPD dosent support with any evidence.Copyright © 2022, Anka Publishers. All rights reserved.

Baskiran, Y., et al. (2023). "The impact of maternal electrolyte and albumin levels on the efficacy of single-dose methotrexate treatment for ectopic pregnancies." Turkish Journal of Obstetrics and Gynecology 20(3): 214-218.
	Objective: This study aims to investigate the impact of maternal albumin and serum electrolyte levels on the efficacy of single-dose methotrexate (SD-Mtx) therapy for ectopic pregnancies. Building on previous research, recommendations are provided to enhance the success of SD-Mtx therapy in the management of ectopic pregnancy. Material(s) and Method(s): Conducted at a tertiary center gynecology clinic, the study included 353 patients diagnosed with ectopic pregnancy and treated with SD-Mtx from 2012 to 2023. Patients who responded positively to SD-Mtx treatment comprised Group 1 (n=313), while those requiring surgical intervention due to failed SD-Mtx therapy constituted Group 2 (n=40). Through the hospital's digital database, patient data including complete blood count, biochemistry, and hormone test results were retrospectively examined. Result(s): The mean beta-hCG value was 1996 IU/mL for Group 1 in contrast to 2058 IU/mL for Group 2. There was no statistically significant difference in beta-hCG levels between the two groups. Notably, Group 1 patients exhibited lower serum magnesium levels but higher potassium levels compared to Group 2 patients, with statistically significant differences. Furthermore, Group 1 patients had higher albumin levels than those in Group 2, with a statistically significant difference. Conclusion(s): Successful SD-Mtx treatment was associated with lower maternal serum magnesium levels and higher potassium and albumin levels. Considering electrolyte levels before administering SD-Mtx and addressing any imbalances could potentially enhance treatment success. Additionally, restoring low albumin levels might improve the efficacy of SD-Mtx treatment for ectopic pregnancies. While this study suggests these trends, further extensive studies with a larger sample size are necessary to establish more definitive evidence.Copyright © 2023, Turkish Society of Obstetrics and Gynecology. All rights reserved.

Basnet, R. (2021). "Impact of pelvic floor muscle training in pelvic organ prolapse." International Urogynecology Journal 32(6): 1351-1360.
	Introduction and hypothesis: This review article was aimed at evaluating the effectiveness of pelvic floor muscle training (PFMT) during conservative management and as an adjunct to prolapse surgery based on recently published articles. Method(s): The PubMed and PEdro databases were searched from 2005 to 2020 for all types of studies reporting on PFMT as the primary treatment for conservative management of prolapse as well as an adjunct for prolapse surgery. Result(s): The result of this review demonstrated that PFMT is effective in conservative management, especially in women with mild to moderate prolapse(stages I-III), for those who wish to have more children, who are not willing to undergo surgery, who are frail because of co-morbidities, and for those who need to delay surgery. However, results evaluating the effectiveness of PFMT as an adjunct to surgery demonstrated insufficient evidence to support the benefit of PFMT in addition to prolapse surgery over the use of surgery alone. Conclusion(s): Through this review, we have concluded that PFMT shows a more prominent effect when applied as conservative management. Currently available evidence demonstrated no additional clinically significant augmentation of PFMT as an adjunct to surgery compared with prolapse surgery alone.Copyright © 2021, The International Urogynecological Association.

Bassel, H. A. W. and R. Michael (2021). "Fresh vs frozen embryo transfer in women with polycystic ovary syndrome: a systematic review and meta-analysis."
	
Bastawros, D., et al. (2021). "Twice-Daily Nitrofurantoin Administration Following Short-term Transurethral Catheterization After Pelvic Reconstructive Surgery: a Randomized Clinical Trial." Female Pelvic Medicine & Reconstructive Surgery 27(3): 202‐207.
	OBJECTIVE: The objective of this study was to evaluate if twice‐daily nitrofurantoin for 5 days after discontinuation of transurethral catheterization decreases the rate of urinary tract infection (UTI) in women with postoperative urinary retention (POUR) after pelvic reconstructive surgery. METHODS: This was a double‐blind, placebo‐controlled, randomized trial conducted across 2 clinical sites between October 2017 and April 2019. Women with acute POUR after pelvic reconstructive surgery were included and randomized to nitrofurantoin (100 mg) or placebo twice‐daily for 5 days. The primary outcome was clinically suspected UTI (defined as dysuria, frequency, and irritation in the absence of vaginal discharge) and/or culture‐proven UTI (defined as greater than 105 colony forming units of a single organism) within 30 days of surgery. Secondary outcomes included evaluation of adverse events related to study medication and medication adherence. RESULTS: Data from 164 participants were eligible for intention‐to‐treat analysis (nitrofurantoin, n = 82; placebo, n = 82). There were no significant demographic or intraoperative differences except for body mass index and race. Median duration of catheterization was 3 days (interquartile range, 2‐5 days, P = 0.12). Fifteen women in the nitrofurantoin group and 14 women in the placebo group experienced UTI within 30 days (18.3% vs 17.1%; P = 0.84; odds ratio, 1.09; 95% confidence interval, 0.49‐2.43). There were no study medication allergies; however, nausea was the most common intolerance. Most women in each group completed the study drug treatment (91.5% vs 86.4%, P = 0.30). CONCLUSIONS: Nitrofurantoin prophylaxis after transurethral catheter removal did not reduce the risk of UTI in women with acute POUR after pelvic reconstructive surgery.

Batista, T., et al. (2021). "A phase II trial of short-course Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) for high tumor burden ovarian cancer: updated report with preliminary survival outcomes." Gynecologic Oncology 162(Supplement 1): S78.
	Objectives: To present an updated report with preliminary survival outcomes from our feasibility study. Method(s): This study was a non-randomized, open-label, multi-center, single-arm trial on the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by fast-track cytoreductive surgery (CRS) plus short-course HIPEC (i.e.: 30 min) in advanced ovarian cancer (NCT02249013). HIPEC was performed according to the closed-abdomen technique using a concentration-based regimen of cisplatin (25 mg/m2/L) or cisplatin plus doxorubicin (15mg/L) at 41-43degreeC. Dextrose perfusate was circulated using the Performer HT device (RAND Srl, Medolla, MO, Italy) at a flow rate of 700ml/min. Primary endpoint was PD9 (i.e.: proportion of patients with disease progression or death occurring within 9 months of interval CRS plus HIPEC) and secondary endpoints were morbidity (mortality and complication rates related to CRS plus HIPEC), time to start adjuvant chemotherapy, length of ICU and hospital stay, QoL over treatment (EORTC QLQ-C30), and ultimately progression-free (PFS) and overall (OS) survivals. Funding sources were from Decit/SCTIE/MS - CNPq/FACEPE/SES-PE (APQ:0187-4.01/13) and FAPE/IMIP. Result(s): A total of 15 patients with stage III epithelial malignancies were recruited from our public health system between February 2015 and July 2019 in four Brazilian centers. The median (range) age was 46 years (19-67), with preoperative serum CA125 levels of 737.7U/mL (161.6-6550). The median number of preoperative cycles of IV chemotherapy was 3 (2-4), resulting in PCI scores of 11 (3-18) at the time of interval CRS plus HIPEC performed after a median of 29 days (26-43) from the last neoadjuvant cycle. Time to restarts IV chemotherapy was 39 days (31-74) and fourteen (93.3%) patients completed all the six cycles of IV chemotherapy as planned. Only 1 patient did not start the systemic adjuvant therapy due to poor recovery after surgery. Median operation time was 490 minutes (235-865), with 9 (60%) patients requiring major bowel resection as rectosigmoidectomy (n=8) or partial colectomy (n=1), but with a nil rate of ostomies. Median length of hospital stay was 5 days (3-10), with ICU stay of 1 day (1-5). Four patients experienced no postoperative complications, whereas 5 suffered only minor G1/G2 complications, and 6 suffered major G3 complications, according to the NCI/CTCAE classification. The most common complications were electrolytes imbalance and anemia. Two patients experienced reoperation because of G3 postoperative hemorrhage or peritoneal infection, whereas no deaths were recorded. No significant difference over time in the QLQ-C30 summary scores was observed (p>0.05). With a median follow-up of 32 (18.2-61.2) months, PD9 and median PFS was 6.7% and 18 months, respectively. At this time, median OS was not reached and our 2y- PFS and OS was 30.8% and 92.8%, respectively. Conclusion(s): We confirm the preliminary hypothesis of safety and efficacy for our comprehensive approach involving the use of short-course HIPEC in high tumor burden ovarian cancer. Median overall survival is pending to confirm short-course HIPEC at the time of interval CRS as a promising approach in terms of survival outcomes.Copyright © 2021 Elsevier Inc.

Batman, S., et al. (2021). "Trastuzumab with carboplatin/paclitaxel for treatment of advanced stage and recurrent uterine papillary serous carcinoma: A cost-effectiveness analysis." Gynecologic Oncology 160(1): 214-218.
	Objective: Uterine papillary serous carcinoma (UPSC) is a variant of endometrial cancer that is aggressive and associated with poor outcomes. We sought to evaluate the cost effectiveness of carboplatin/paclitaxel alone versus carboplatin/paclitaxel with trastuzumab among patients with Her2/neu-positive advanced or recurrent UPSC. Method(s): We designed a Markov model in TreeAge Pro 2019 software to simulate management of a theoretical cohort of 4000 patients with Her2/neu-positive advanced or recurrent uterine papillary serous carcinoma (UPSC) followed for four years. In the carboplatin/paclitaxel with trastuzumab strategy, we included the cost of testing for Her2/neu status. We obtained all model inputs from the literature and a societal perspective was assumed. Outcomes included progression-free survival, progression, UPSC-specific mortality, cost, and quality-adjusted life years (QALYs). The intervention was considered cost effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were used to determine the robustness of the results. Result(s): In our theoretical cohort of 4000 women, treatment with the addition of trastuzumab resulted in 637 fewer deaths and 627 fewer cases of progression compared with treatment with carboplatin/paclitaxel alone. Treatment with trastuzumab was associated with an additional cost of $144,335,895, but was associated with an increase of 2065 QALYs. The ICER was $69,903 per QALY, which was below our willingness-to-pay threshold. Sensitivity analysis demonstrated that this treatment strategy was cost-effective until the cost of 6 months of treatment surpassed $38,505 (baseline input: $27,562). Conclusion(s): We found that the addition of trastuzumab to carboplatin/paclitaxel was a cost-effective treatment strategy for patients with advanced/recurrent Her2/neu-positive UPSC.Copyright © 2020 Elsevier Inc.

Batur, P. (2021). "In postmenopausal women, multimodal or US screening for ovarian cancer did not reduce ovarian cancer mortality." Annals of Internal Medicine 174(10): JC114.
	Menon U, Gentry-Maharaj A, Burnell M, et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2021;397:2182-93. 33991479.

Bauer Todd, M., et al. (2023). "A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors." Targeted oncology 18(4): 517-530.
	Background: Adavosertib (AZD1775) is a first-in-class, selective, small-molecule inhibitor of Wee1.; Objective: The safety, tolerability, pharmacokinetics, and efficacy of adavosertib monotherapy were evaluated in patients with various solid-tumor types and molecular profiles.; Patients and Methods: Eligible patients had the following: confirmed diagnosis of ovarian cancer (OC), triple-negative breast cancer (TNBC), or small-cell lung cancer (SCLC); previous treatment for metastatic/recurrent disease; and measurable disease. Patients were grouped into six matched cohorts based on tumor type and presence/absence of biomarkers and received oral adavosertib 175 mg twice a day on days 1-3 and 8-10 of a 21-day treatment cycle.; Results: Eighty patients received treatment in the expansion phase; median total treatment duration was 2.4 months. The most common treatment-related adverse events (AEs) were diarrhea (56.3%), nausea (42.5%), fatigue (36.3%), vomiting (18.8%), and decreased appetite (12.5%). Treatment-related grade ≥ 3 AEs and serious AEs were reported in 32.5% and 10.0% of patients, respectively. AEs led to dose interruptions in 22.5%, reductions in 11.3%, and discontinuations in 16.3% of patients. One patient died following serious AEs of deep vein thrombosis (treatment related) and respiratory failure (not treatment related). Objective response rate, disease control rate, and progression-free survival were as follows: 6.3%, 68.8%, 4.5 months (OC BRCA wild type); 3.3%, 76.7%, 3.9 months (OC BRCA mutation); 0%, 69.2%, 3.1 months (TNBC biomarker [CCNE1/MYC/MYCL1/MYCN] non-amplified [NA]); 0%, 50%, 2 months (TNBC biomarker amplified); 8.3%, 33.3%, 1.3 months (SCLC biomarker NA); and 0%, 33.3%, 1.2 months (SCLC biomarker amplified).; Conclusion: Adavosertib monotherapy was tolerated and demonstrated some antitumor activity in patients with advanced solid tumors.; Trial Registration: ClinicalTrials.gov identifier NCT02482311; registered June 2015. (© 2023. The Author(s).)

Bautrant, E., et al. (2022). "PHASE-III Randomized monocentric controlled trial comparing clinical and cost-effectiveness analysis of botulinum toxin uterine injections versus placebo for severe dysmenorrhea and chronic pelvic pain from uterine origin after standard therapeutic failure." European journal of obstetrics gynecology and reproductive biology. Conference: EBCOG 2021. European congress of obstetrics and gynaecology 270: e102.
	Introduction and aims of the study: severe dysmenorrhea and chronic pelvic pain (CPP) from uterine origin may be followed by psycho‐social consequences and professional absenteism. Despite a negative magnetic resonance imaging and laparoscopy, current available treatments (analgesics, anti‐inflammatory drugs and hormones) are ineffective with low quality of life gains. As published previously, injections of botulinum toxin (BT) type A under hysteroscopy into uterine myometrium revealed significant decrease of patient‐reported symptoms and improvement of global quality of life scores at 8 and 12‐week post‐injection. The aims of this study are to evaluate clinical and cost‐effectiveness of BT use for severe dysmenorrhea/CPP after treatment failure. Methods: phase‐III randomized monocentric controlled trial comparing BT versus placebo among 100 participants. Randomization will be centralized. Study investigators, analysis team, and subjects will remain blinded. Participants will be informed and will sign a written informed consent. Data will be collected and registered in a secure electronic platform before enrollment, at inclusion, 8‐week and 4‐month follow‐up. Main clinical outcome: patient Global Impression of Improvement. Secondary clinical outcomes: health‐Related Quality of Life (HRQoL) by Endometriosis Health Profile, Generic HRQoL EQ‐5D‐3L, Female Sexual Function Index, dysmenorrhea and dyspareunia numerical rating scale, pain visual analogue scale, side effects, drug tolerance, surgical complications, global patient satisfaction. Effectiveness and costs outcomes: quality‐adjusted life years (QALYs), direct and indirect costs, net social benefit, incremental cost‐effectiveness ratios. Discussion: this study will provide the most reliable evidence on the effectiveness of a novel therapy for patients suffering from severe dysmenorrhea and CPP from uterine origin, in the event of standard therapeutic failure. The health economic evaluation will give evidence to guide collective decision‐making on marketing authorization for this clinical indication. Conclusions: evidence‐based clinical and cost‐effectiveness of BT will guide the proposal and implementation of a new treatment for severe dysmenorrhea and CPP from uterine origin

Bayefsky, M., et al. (2022). "Navigating parent-child disagreement about fertility preservation in minors: scoping review and ethical considerations." Human Reproduction Update 28(5): 747-762.
	Background: Offering fertility preservation (FP) prior to gonadotoxic therapy, including cancer care and gender-affirming treatment, is now considered standard of care. Periodically, parents and children disagree about whether to pursue FP. However, it is unknown how often this occurs and how disagreement is handled when it arises. Moreover, there is no clear guidance on how to resolve these difficult situations.; Objective and Rationale: The purpose of this scoping review is to provide an overview of available research evidence about parent-child disagreement regarding FP in order to establish that disagreement occurs in practice, understand the basis for disagreement and explore suggestions for how such disputes could be resolved. Based on our findings, we offer a discussion of the ethical principles at stake when disagreement occurs, which can be used to guide clinicians' approaches when these challenging scenarios present.; Search Methods: A comprehensive literature search was run in several databases, including PubMed/Medline, Embase and the Cochrane Library. The search was performed in February 2021 and updated in August 2021. Articles were included in the final review if they discussed how parents or children wanted their views on FP taken into account, presented evidence that parent-child discordance regarding FP exists, discussed how to handle disagreement in a particular case or offered general suggestions for how to approach parent-child discordance about FP. Studies were excluded if the patients were adult only (age 18 years and older), pertained to fertility-sparing treatments (e.g. gonad shielding, gonadopexy) rather than fertility-preserving treatments (e.g. testicular tissue cryopreservation, ovarian tissue cryopreservation, oocyte cryopreservation or sperm cryopreservation) or explored the views of clinicians but not patients or parents. Meta-synthesis was used to synthesize and interpret data across included studies and thematic analysis was used to identify common patterns and themes.; Outcomes: In total, 755 publications were screened, 118 studies underwent full-text review and 35 studies were included in the final review. Of these studies, 7 discussed how parents or children wanted their opinions to be incorporated, 11 presented evidence that discordance exists between parents and children regarding FP, 4 discussed how disagreement was handled in a particular case and 21 offered general suggestions for how to approach parent-child disagreement. There was a range of study designs, including quantitative and qualitative studies, case studies, ethical analyses and commentaries. From the thematic analysis, four general themes regarding FP disagreement emerged, and four themes relating to the ethical principles at stake in parent-child disagreement were identified. The general themes were: adolescents typically desire to participate in FP decision-making; some parents prefer not to involve their children; minors may feel more favorably about FP than their parents; and transgender minors and their parents may have unique reasons for disagreement. The ethical principles that were identified were: minor's best interest; right to an open future; minor's autonomy; and parental autonomy.; Wider Implications: This study offers an overview of available research on the topic of parent-child disagreement regarding FP and discusses the ethical considerations at stake when disagreement occurs. The findings can be used to inform guidance for clinicians presented with FP disagreement in practice. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Bayer (2021). A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause (OASIS-2).
	No Results Available Drug: Elinzanetant (BAY3427080)|Drug: Placebo Mean change in frequency of moderate to severe hot flash (HF) from baseline to Week 4 (assessed by hot flash daily diary [HFDD])|Mean change in frequency of moderate to severe HF from baseline to Week 12 (assessed by HFDD)|Mean change in severity of moderate to severe HF from baseline to Week 4 (assessed by HFDD)|Mean change in severity of moderate to severe HF from baseline to Week 12 (assessed by HFDD)|Mean change in frequency of moderate to severe HF from baseline to Week 1 (assessed by HFDD)|Mean change in frequency of moderate to severe HF from baseline over time|Mean change in patient-reported outcomes measurement information system sleep disturbance short form 8b (PROMIS SD SF 8b) total score from baseline to Week 12|Mean change in menopause specific quality of life scale (MENQOL) total score from baseline to Week 12|Mean change in Beck depression inventory (BDI-II) total score from baseline to Week 12|Mean change in BDI-II total score from baseline to Week 26 Female Phase 3 400 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 21652|2020-004855-34 October 4, 2023

Bayer (2023). A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated With Menopause.
	No Results Available Drug: Elinzanetant|Other: Placebo Change from baseline in WASO as measured by PSG|Change from baseline in SE as measured by PSG|Change from baseline in PROMIS SD SF 8b total score|Change from baseline in ISI total score|Number of participants with Treatment-emergent Adverse Events (TEAEs)|Number of participants with Abnormal laboratory parameters Female Phase 2 78 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 22423|2023-504955-28-00 January 7, 2025

Bazzazian, S., et al. (2021). "The relationship between depression, stress, anxiety, and postpartum weight retention: A systematic review." Journal of education and health promotion 10: 230.
	Postpartum weight retention (PPWR) is a factor that causes permanent obesity and subsequent chronic and noncommunicable diseases. The relationship between depression/stress/anxiety and PPWR has been studied in some articles, but there is no definitive conclusion in this regard. The present systematic review was conducted to investigate the relationship between depression/stress/anxiety and PPWR. An extensive search was performed in the PubMed, Scopus, Embase, Web of Science, Google Scholar, SID, and Magiran, Irandoc databases using Medical Subject Headings terms (or their Persian synonyms) from 2000 to 2020. Inclusion and exclusion criteria were used for articles selection. The quality of the selected articles was assessed using the Newcastle-Ottawa Scale. Out of 371 reviewed articles, 24 articles were selected. The total sample size was 51,613 (range: 49-37,127). The mean of PPWR ranged from 0.5 kg (standard deviation [SD] = 6.49) to 6.4 kg (SD = 8.5). There was a statistically significant relationship between depression/stress/anxiety and PPWR in 12 of 23, 4 of 6, and 3 of 8 studies. This review demonstrates the relationship between depression/stress/anxiety and PPWR. Time of depression/stress/anxiety assessment is an important issue, as well as different measurement tools. Prevention of the mothers' psychological problems through educational and supportive programs may help to limit PPWR.

Bear Katie, A., et al. (2022). "The Impact of a Mindfulness App on Postnatal Distress." Mindfulness 13(11): 2765-2776.
	Objectives: The present study investigated the effectiveness of an 8-week mindfulness mobile phone app on women's depression, anxiety, stress and mindful attention/awareness in the postnatal period.; Methods: The study enrolled 99 mothers of a child under 1 year old, and randomly assigned them to intervention ( n = 49, mean age = 31.11, SD = 4.30, years) and control ( n = 50, mean age = 31.35, SD = 5.29, years) groups. Multiple regression examined intervention effects on depression, anxiety, stress and mindful attention/awareness measured post-intervention and at 4-week follow-up, controlling for the baseline and post-intervention measurement of the specific outcome, respectively.; Results: The intervention group showed significant decreases in depression, anxiety and stress levels and an increase of mindful attention/awareness post-intervention compared to the control group, with medium to large effect sizes after controlling for effects of corresponding variables at baseline. The intervention group showed further decrease in depression and stress levels and an increase in mindful attention/awareness at 4 weeks post-intervention compared to the control group, with small to medium effect sizes, after controlling for effects of corresponding variables at post-intervention.; Conclusions: The outcomes of the study suggest that delivery of mindfulness via smartphones could be a viable and affordable resource for reducing postnatal depression, anxiety and stress.; Competing Interests: Conflict of InterestThe authors declare no competing interests. (© The Author(s) 2022.)

Beaucage-Charron, J., et al. (2022). "A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study." Supportive Care in Cancer 30(4): 3389-3399.
	Purpose: Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR. Method(s): This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome). Result(s): Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (DELTASSS) was greater in the diphenhydramine group compared to the cetirizine group (median DELTASSS 2 (IQR 3.25) vs median DELTASSS 0 (IQR 1), p < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred. Conclusion(s): The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. Trial registration: ClinicalTrials.gov, NCT04237090 (22.01.2020).Copyright © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Beauchamp, U. L., et al. (2020). "The Use of Wearables in Clinical Trials During Cancer Treatment: Systematic Review." JMIR mHealth and uHealth 8(11): e22006.
	BACKGROUND: Interest in the use of wearables in medical care is increasing. Wearables can be used to monitor different variables, such as vital signs and physical activity. A crucial point for using wearables in oncology is if patients already under the burden of severe disease and oncological treatment can accept and adhere to the device. At present, there are no specific recommendations for the use of wearables in oncology, and little research has examined the purpose of using wearables in oncology. OBJECTIVE(S): The purpose of this review is to explore the use of wearables in clinical trials during cancer treatment, with a special focus on adherence. METHOD(S): PubMed and EMBASE databases were searched prior and up to October 3, 2019, with no limitation in the date of publication. The search strategy was aimed at studies using wearables for monitoring adult patients with cancer during active antineoplastic treatment. Studies were screened independently by 2 reviewers by title and abstract, selected for inclusion and exclusion, and the full-text was assessed for eligibility. Data on study design, type of wearable used, primary outcome, adherence, and device outcome were extracted. Results were presented descriptively. RESULT(S): Our systematic search identified 1269 studies, of which 25 studies met our inclusion criteria. The types of cancer represented in the studies were breast (7/25), gastrointestinal (4/25), lung (4/25), and gynecologic (1/25); 9 studies had multiple types of cancer. Oncologic treatment was primarily chemotherapy (17/25). The study-type distribution was pilot/feasibility study (12/25), observational study (10/25), and randomized controlled trial (3/25). The median sample size was 40 patients (range 7-180). All studies used a wearable with an accelerometer. Adherence varied across studies, from 60%-100% for patients wearing the wearable/evaluable sensor data and 45%-94% for evaluable days, but was differently measured and reported. Of the 25 studies, the most frequent duration for planned monitoring with a wearable was 8-30 days (13/25). Topics for wearable outcomes were physical activity (19/25), circadian rhythm (8/25), sleep (6/25), and skin temperature (1/25). Patient-reported outcomes (PRO) were used in 17 studies; of the 17 PRO studies, only 9 studies reported correlations between the wearable outcome and the PRO. CONCLUSION(S): We found that definitions of outcome measures and adherence varied across studies, and limited consensus among studies existed on which variables to monitor during treatment. Less heterogeneity, better consensus in terms of the use of wearables, and established standards for the definitions of wearable outcomes and adherence would improve comparisons of outcomes from studies using wearables. Adherence, and the definition of such, seems crucial to conclude on data from wearable studies in oncology. Additionally, research using advanced wearable devices and active use of the data are encouraged to further explore the potential of wearables in oncology during treatment. Particularly, randomized clinical studies are warranted to create consensus on when and how to implement in oncological practice.Copyright ©Ulrikke Lyng Beauchamp, Helle Pappot, Cecilie Hollander-Mieritz. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 11.11.2020.

Beauquier-Maccotta, B. (2021). "Post-natal Post-traumatic Stress: Impact of an Early Dyadic Intervention Though Interaction Guidance Therapy on Maternal Sensitivity and Reduction of Maternal Stress." ClinicalTrials.gov.
	No Results Available Behavioral: Interaction Guidance Therapy|Behavioral: Mother's child psychotherapeutic session|Behavioral: Interview|Behavioral: Self-rated questionnaires Maternal sensitivity|Maternal sensitivity at 12 months|Prevalence of PN-PTSD|Prevalence of post natal depressive symptoms|Infant development ASQ|Infant symptoms SCL|fathers' Post-traumatic stress disorder|Father's depressive symptoms|both parents' anxiety|both parents' perception of social support|both parents' perception of their marital relationship|both parents' bonding to the child All Not Applicable 90 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment APHP180615|ID-RCB Number December 2024

Becattini, C., et al. (2020). "Updated meta-analysis on prevention of venous thromboembolism in ambulatory cancer patients." Haematologica 105(3): 838-848.
	Randomized clinical trials have evaluated the role of anticoagulants in the prevention of venous thromboembolism (VTE) in ambulatory cancer patients treated with chemotherapy. This meta-analysis is aimed at providing an updated evaluation of the efficacy and safety of anticoagulant prophylaxis in this clinical setting. Medline and Scopus were searched to retrieve randomized controlled trials on the prevention of VTE in ambulatory cancer patients. Two groups of trials were identified with VTE or death as the primary outcome, respectively. VTE was the primary outcome of this analysis. Anticoagulant prophylaxis reduced the incidence of VTE in studies in which the primary outcome was VTE [14 studies, 8,226 patients; odds ratio (OR)=0.45; 95% confidence interval (95% CI): 0.36- 0.56] or death (8 studies, 3,727 patients; OR=0.61; 95% CI: 0.47-0.81). When these studies were pooled together, VTE was reduced by 49% (95% CI: 0.43-0.61) with no significant increase in major bleeding (OR=1.30, 95% CI: 0.98-1.73). The risk of major bleeding was increased in studies with VTE as the primary outcome (OR=1.43, 95% CI: 1.01-2.04). Similar reductions of VTE were observed in studies with parenteral (OR=0.43, 95% CI: 0.33- 0.56) or oral anticoagulants (OR=0.49, 95% CI: 0.33-0.74). The reduction in VTE was confirmed in patients with lung (OR=0.42, 95% CI: 0.26-0.67) or pancreatic cancer (OR=0.26, 95% CI: 0.14-0.48), in estimated high-risk patients, in high-quality studies and with respect to symptomatic VTE. In conclusion, prophylaxis with oral or parenteral anticoagulants reduces the risk of VTE in ambulatory cancer patients, with an acceptable increase in major bleeding.Copyright ©2020 Ferrata Storti Foundation

Bechini, A., et al. (2023). "Efficacy of HPV Vaccination Regarding Vulvar and Vaginal Recurrences in Previously Treated Women: The Need for Further Evidence." Vaccines 11(6).
	Vulvar and vaginal cancers are relatively rare cancers, but their incidence is increasing worldwide. Overall, 78% of vaginal cancers and 25% of vulvar cancers are associated with Human papillomavirus (HPV) infection. Immunization could be an option for the management of these cases. We researched and assessed the evidence on the efficacy of HPV vaccination administered to women previously treated with surgery, radiotherapy, or chemotherapy with respect to the recurrence of vulvovaginal disease. From 2006 to November 2022, only one study evaluated the efficacy of HPV vaccination with respect to preventing vulvovaginal recurrences in treated women and showed that a quadrivalent HPV vaccine administered after the surgical treatment of vulvar high-grade squamous intraepithelial lesion (HSIL) can reduce vulvar recurrence of the disease. Therefore, the efficacy of HPV vaccination with respect to vulvovaginal recurrence is still an unexplored field. Further studies are needed to produce stronger evidence in order to appropriately support interventions to protect women's health.

Beck, C. T. and S. Casavant (2019). "Synthesis of Mixed Research on Posttraumatic Stress Related to Traumatic Birth." Journal of obstetric, gynecologic, and neonatal nursing : JOGNN 48(4): 385-397.
	OBJECTIVE: To synthesize mixed-research results (quantitative and qualitative) on posttraumatic stress in women who experienced traumatic births. DATA SOURCES: PubMed, Scopus, and PsycINFO databases. STUDY SELECTION: Quantitative and qualitative studies were included if they were published in English from January 1, 2009, through December 31, 2018, and focused on posttraumatic stress in the postpartum period related to traumatic childbirth. DATA EXTRACTION: The final sample consisted of 59 studies: 4 qualitative and 55 quantitative. Both authors independently appraised each study using the Critical Appraisal Skills Programme. Quantitative studies were synthesized by narrative synthesis and vote counting, and qualitative studies were synthesized by content analysis. DATA SYNTHESIS: In the included studies, prevalence rates of elevated posttraumatic stress ranged from 0.8% to 26%. Significant predictors of posttraumatic stress that occurred before childbirth and those that were birth related were identified. Reports of six intervention studies to decrease posttraumatic stress symptoms after traumatic births were included. These interventions focused on postnatal debriefing, expressive writing, online cognitive behavioral therapy, a brief cognitive intervention, and the implementation of the nine instinctive stages of the infant during the first hour after birth. We created four themes from the findings of the qualitative studies: Distressing Symptoms, Detrimental Effect of Posttraumatic Stress on Women's Relationships With Their Infants and Partners, Critical Influence ofSupport, and Debriefing. CONCLUSION(S): When a woman experiences posttraumatic stress related to a traumatic birth, the entire family unit is vulnerable. Findings from quantitative predictor studies can be used to develop an instrument to screen women for risk factors for posttraumatic stress related to birth trauma. Primary interventions are needed to prevent women from experiencing traumatic births.Copyright © 2019 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

Beck, D., et al. (2022). "Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids." Clinical pharmacokinetics 61(4): 577-587.
	Background and Objectives: Elagolix is an orally active, gonadotropin-releasing hormone receptor antagonist approved for the management of endometriosis-associated pain and heavy menstrual bleeding associated with uterine fibroids. Elagolix population pharmacokinetics and factors affecting elagolix exposure in healthy women and women with endometriosis have been reported previously. The purpose of this study was to extend the population pharmacokinetics model with additional modifications to incorporate data from phase III studies of elagolix with hormonal add-back therapy in women with uterine fibroids.; Methods: Data from 13 clinical studies (a total of 2168 women) consisting of six phase I studies in healthy premenopausal women, four phase III studies in premenopausal women with endometriosis, and three phase III studies in premenopausal women with uterine fibroids were analyzed using a non-linear mixed-effects modeling approach.; Results: Elagolix population pharmacokinetics was best described by a two-compartment model with first-order absorption, lag time in absorption, and first-order elimination. Out of the covariates tested on elagolix apparent clearance, apparent volume of distribution, and/or relative bioavailability, only organic anion transporting polypeptide 1B1 genotype status and body weight had a statistically significant but no clinically meaningful effect on elagolix relative bioavailability and apparent volume of distribution, respectively. There were no clinically meaningful differences in elagolix population pharmacokinetics in healthy women or women with endometriosis or uterine fibroids.; Conclusions: Elagolix population pharmacokinetics modeling did not reveal any patient-related factors or clinical parameters that would require dose adjustments for the approved dosage of 300 mg twice daily with estradiol 1 mg /norethindrone acetate 0.5 mg daily, in women with heavy menstrual bleeding associated with uterine fibroids.; Clinical Trial Registration: ClinicalTrials.gov identifiers: NCT01620528 (EM-1), NCT01760954 (EM-1-Extend), NCT01931670 (EM-2), NCT02143713 (EM-2-Extend), NCT02654054 (UF-1), NCT02691494 (UF-2), NCT0295494 (UF-Extend). (© 2021. The Author(s).)

Becker, C., et al. (2022). "SPIRIT long-term extension study: two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain." Human Reproduction 37(Supplement 1): i110.
	Study question: To assess the long-term efficacy and safety of once-daily Relugolix combination therapy (Relugolix-CT) in the treatment of endometriosis- associated pain over two years. Summary answer: Relugolix-CT previously demonstrated sustained improvement ofendometriosis-associated pain and was generally well tolerated over 52 weeks. Research is ongoing: two-year results will be reported. What is known already: SPIRIT 1&2 were international, Phase 3, replicate, randomized, double-blind, placebo-controlled studies of Relugolix-CT (relugolix 40mg, estradiol 1mg, norethisterone acetate 0.5mg) in premenopausal women with moderate-to-severe endometriosis-associated pain, which were followed by the open-label, 80-week, long-term extension. 52-week results showed sustained improvement in dysmenorrhea and non-menstrual pelvic pain (NMPP) with 84.8% and 73.3% of responders, respectively. Efficacy was evidenced by reductions in dysmenorrhea (82.8%,) NMPP (62.9%,) proportion of women using opioids, and improvements in function. Relugolix-CT was generally well tolerated. Bone mineral density (BMD) assessment showed minimal initial decline (<1%) from baseline followed by stabilization from Week 24 to 52. Study design, size, duration: Women who completed the 24-week pivotal studies (SPIRIT 1&2) were eligible to enroll in an 80-week open-label, singlearm, long-term extension study of safety and efficacy, representing up to 104 weeks of treatment in total. All women enrolled in the long-term extension study received once-daily oral Relugolix-CT. Analyses were performed based on the initial randomized treatment groups in pivotal studies: Relugolix-CT, delayed Relugolix-CT (relugolix 40mg alone for 12 weeks, then Relugolix-CT for 12 weeks), or placebo. Participants/materials, setting, methods: Primary endpoints are proportion of dysmenorrhea and NMPP responders at Weeks 52 and 104 based on daily Numerical Rating Scale (NRS) scores (0=no pain, 10=worst pain imaginable) and analgesic use. Responders are women who achieved a predefined, clinically meaningful reduction from baseline in NRS score and no increase in analgesic use. Secondary efficacy endpoints include change in Endometriosis Health Profile-30 pain domain scores, use of opioids/analgesics. Safety endpoints include adverse events and BMD (percent change). Main results and the role of chance: Of 1251 randomized patients in SPIRIT 1&2, 1044 (83.4%) completed the pivotal studies; 802 (76.8%) enrolled in the long-term extension, and 681 (84.9%) completed 52 weeks of treatment. Baseline demographics and clinical characteristics of the long-term extension population were consistent with those of the pivotal study population. The study remains ongoing at the time of writing. Efficacy and safety data with Relugolix-CT for up to Week 104, will be presented at the scientific session of the 2022 congress. Limitations, reasons for caution: The study was conducted as an open-label study without a control group over the 80 weeks of the extension period. Wider implications of the findings: Through 52 weeks of treatment, Relugolix-CT demonstrated sustained improvement of dysmenorrhea, NMPP, function, and reduced need for opiates in women with endometriosis-associated pain. No new safety concerns were identified, and treatment was associated with BMD loss <1%. Data from 104 weeks of treatment will be presented at the 2022 congress.

Becker, C., et al. (2021). "The effect of time since surgical diagnosis of endometriosis on treatment outcomes with relugolix combination therapy in women with endometriosis-associated pain: SPIRIT program." Human reproduction (Oxford, England) 36(SUPPL 1): i57.
	Study question: To assess the efficacy of Relugolix‐CT vs placebo in women who were surgically diagnosed with endometriosis <5 and >= 5 years ago. Summary answer: Treatment outcomes did not differ for dysmenorrhea and daily functioning between subgroups of patients with <5 years or ≥5 years since surgical diagnosis. What is known already: Time since clinical manifestation and diagnosis of endometriosis may influence the treatment success of patients with endometriosis‐ associated pain. SPIRIT 1 and 2 were randomized, double‐blind, placebo‐ controlled Phase 3 studies of Relugolix‐CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in premenopausal women (age 18‐50 years) with surgically diagnosed endometriosis and a history of moderate‐to‐severe dysmenorrhea and non‐menstrual pelvic pain (NMPP). These studies previously demonstrated that Relugolix‐CT significantly reduced dysmenorrhea and NMPP, and improved daily functioning measured by the Endometriosis Health Profile‐30 (EHP‐30) pain domain score vs placebo over 24 weeks. Study design, size, duration: Premenopausal women with surgically diagnosed endometriosis and moderate‐to‐severe dysmenorrhea and NMPP at baseline were randomized 1:1:1 to 24 weeks of treatment with once daily oral Relugolix‐CT, delayed Relugolix‐CT (relugolix 40 mg monotherapy for 12 weeks followed by Relugolix‐CT for 12 weeks), or placebo. The proportion of dysmenorrhea and NMPP responders at Week 24/End‐of‐Treatment (EoT), based on daily Numerical Rating Scale (NRS), and analgesic use status were co‐primary endpoints. Participants/materials, setting, methods: Pooled SPIRIT 1 and 2 data of patients who received 24 weeks of treatment with once daily Relugolix‐CT (N=418) or placebo (N=416) are presented. Outcomes for the delayed Relugolix‐CT group were only for the safety assessment and therefore not reported here. Analyses of NRS scores for dysmenorrhea, NMPP, and EHP‐30 pain domain score were carried out in the subgroups of patients with time since diagnosis of <5 years (N=579) and ≥5 years (N=255). Main results and the role of chance: Baseline demographics and clinical characteristics were comparable between the time since diagnosis subgroups except for a numerically higher mean age in the ≥5‐years subgroup. Mean time since diagnosis (standard deviation) was 2.1 (1.5) years with both Relugolix‐CT and placebo for <5‐years subgroup, and 8.0 (2.8) and 7.8 (2.3) years, respectively, for ≥5‐years subgroup. In Relugolix‐CT‐treated patients, mean NRS score for dysmenorrhea decreased from 7.5 (severe) to 1.8 (mild) in the <5‐years subgroup and from 6.9 (moderate) to 1.8 (mild) in the ≥5‐years subgroup with a significant difference to placebo (p<0.0001, both subgroups), and demonstrating 74.8% and 72.7% reduction in pain from baseline to Week 24/EoT, respectively. Mean NRS score for NMPP decreased from 6.0 (moderate) to 3.0 (mild) with a significant difference compared with placebo (p<0.0001), equating to 48.8% pain reduction in the <5‐years subgroup, and from 5.6 (moderate) to 2.7 (mild) equating to 51.5% pain reduction (p=0.089) in the ≥5‐years subgroup. Improvement of daily functioning as measured by EHP‐30 pain domain score was significantly greater with Relugolix‐CT vs placebo in both subgroups, with decrease in EHP‐30 pain score from 59.1 to 24.0 in the <5‐years subgroup, and from 57.4 to 21.1 in the ≥5‐years subgroup (p<0.0001, both subgroups). Limitations, reasons for caution: A lower number of patients were included into the subgroup with ≥5‐years since surgically diagnosed endometriosis. Fiveyear dichotomy was close to the mean time since surgical diagnosis in the studies and to certain extent is arbitrary. Furthermore, time since surgical diagnosis is not the same as time since symptom onset. Wider implications of the findings: In women with endometriosis‐associated pain, Relugolix‐CT vs placebo significantly reduced dysmenorrhea and improved daily functioning in both groups: wit urgical diagnosis of <5 years or ≥5 years. Substantial decrease in NMPP was also observed and was significantly different to placebo in the <5‐years subgroup.

Becker, C., et al. (2023). "Effect of relugolix combination therapy in women with endometriosis-associated pain who received prior first-line hormonal treatment: SPIRIT 1 and 2." Human Reproduction 38(Supplement 1): i17-i18.
	Study question: To assess the effect of oral relugolix combination therapy (Relugolix-CT) in the subgroup of women with endometriosis-associated pain who received prior first-line hormonal treatment. Summary answer: Relugolix-CT significantly reduced dysmenorrhoea and non-menstrual pelvic pain (NMPP) through 24 weeks in women with endometriosis-associated pain who received prior first-line hormonal treatment. What is known already: ESHRE recommends hormonal contraceptives or progestogens as first-line therapy for endometriosis; however, these treatments may not be efficacious for all women. SPIRIT 1&2 were Phase 3, replicate, randomised studies of oral Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) in premenopausal women (aged 18-50 years) with moderate-to-severe endometriosis-associated pain. In SPIRIT 1&2, Relugolix-CT significantly improved dysmenorrhoea, NMPP and daily functioning (measured by the Endometriosis Health Profile-30 pain domain score) compared with placebo over 24 weeks. Relugolix-CT was well-tolerated and bone mineral density showed a minimal decline (<1%) from baseline to Week 24. Study design, size, duration: At screening, women were required to have at least moderate menstrual and non-menstrual pain during their last cycle. In total, 1261 women with diagnosed endometriosis and moderate-to-severe dysmenorrhoea and NMPP at baseline were randomised 1:1:1 to receive once-daily Relugolix-CT or placebo for 24 weeks, or delayed Relugolix-CT (relugolix 40 mg then Relugolix-CT; 12 weeks each). Study candidates who received hormonal treatment for endometriosis completed a washout period prior to the screening and run-in period. Participants/materials, setting, methods: Analyses were performed using pooled SPIRIT 1&2 data in women previously receiving first-line hormonal treatment (e.g. oral contraceptives and/or progestogens; N=392). Co-primary endpoints: proportion of dysmenorrhoea and NMPP responders at Week 24. Responders were women achieving a predefined, clinically meaningful reduction from baseline in daily Numerical Rating Scale (NRS [0=no pain, 10=worst pain imaginable]) score and no increase in analgesic use. Least squares (LS) mean changes in NRS scores were assessed by a mixedeffects model. Main results and the role of chance: In total, 121 women in the Relugolix-CT group and 134 in the placebo group had received prior first-line hormonal treatment, of which combined oral contraceptives and/or dienogest were the most common medications. Data for the delayed Relugolix-CT group were used for safety assessment only and are not reported here. Baseline demographics and clinical characteristics were comparable between the subgroup of women who received prior first-line hormonal treatment and the overall study population. In this subgroup, the proportion of dysmenorrhoea responders with Relugolix-CT vs placebo at Week 24 was 70.2% vs 27.6%, respectively (p<0.0001); the proportion of NMPP responders was 60.3% vs 40.3%, respectively (p=0.0013). In the Relugolix-CT group, LS mean NRS scores for dysmenorrhoea decreased from 7.2 (severe) at baseline to 1.7 (mild) at Week 24, with a significant change from baseline vs placebo (p<0.0001). LS mean NRS scores for NMPP decreased from 5.6 (moderate) at baseline to 2.8 (mild) at Week 24 with Relugolix-CT, with a significant change from baseline vs placebo (p=0.0097). The proportion of women who were analgesic-free at baseline was 7.4% with Relugolix-CT and 3.7% with placebo; this increased to 48.8% with Relugolix-CT and 18.7% with placebo at Week 24 (p<0.0001). Limitations, reasons for caution: Assessment of endometriosis-associated pain at screening visit was done after the wash-out period; therefore, data for endometriosis symptoms experienced by women while receiving hormonal treatment prior to study entry, as well as the duration of the previous treatments, were not available. Wider implications of the findings: Relugolix-CT significantly reduced dysmenorrhoea and NMPP, vs placebo, through 24 weeks in women with endometriosis-a sociated pain who received prior first-line hormonal treatment. The proportion of women in this subgroup who were analgesic-free increased through 24 weeks with Relugolix-CT. Results were comparable to the overall SPIRIT 1&2 population.

Becker Christian, M., et al. (2022). "ESHRE guideline: endometriosis." Human Reproduction Open 2022(2): hoac009.
	Study Question: How should endometriosis be diagnosed and managed based on the best available evidence from published literature?; Summary Answer: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer.; What Is Known Already: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility.; Study Design Size Duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review.; Participants/materials Setting Methods: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee.; Main Results and the Role of Chance: This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected.; Limitations Reasons for Caution: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations.; Wider Implications of the Findings: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis.; Study Funding/competing Interests: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Rich er and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare.; Disclaimer: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type . ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.). (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Becker, C. M., et al. (2024). "Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study." Human Reproduction 39(3): 526-537.
	STUDY QUESTION: What is the efficacy and safety of long-term treatment (up to 2 years) with relugolix combination therapy (CT) in women with moderate to severe endometriosis-associated pain? SUMMARY ANSWER: For up to 2 years, treatment with relugolix CT improved menstrual and non-menstrual pain, dyspareunia, and function in women with endometriosis; after an initial decline of <1%, the mean bone mineral density (BMD) remained stable with continued treatment. WHAT IS KNOWN ALREADY: Endometriosis is a chronic condition characterized by symptoms of dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia, which have a substantial impact on the lives of affected women, their partners, and families. SPIRIT 1 and 2 were phase 3, randomized, double-blind, placebo-controlled studies of once-daily relugolix CT (relugolix 40 mg, oestradiol 1 mg, norethisterone acetate 0.5 mg) in premenopausal women (age 18-50 years) with endometriosis and moderate-to-severe dysmenorrhea and NMPP. These trials demonstrated a significant improvement of dysmenorrhea, NMPP, and dyspareunia in women treated with relugolix CT, with minimal decline (<1%) in BMD versus placebo at 24 weeks. STUDY DESIGN, SIZE, DURATION: Patients participating in this open-label, single-arm, long-term extension (LTE) study of the 24-week SPIRIT pivotal studies (SPIRIT 1 and 2) received up to an additional 80 weeks of once-daily oral relugolix CT treatment between May 2018 and January 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal women with confirmed endometriosis and moderate to severe dysmenorrhea and NMPP who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials; Giudice et al., 2022) and who met all entry criteria were eligible to enrol. Two-year results were analysed by treatment group based on original randomization in pivotal studies: relugolix CT, delayed relugolix CT (relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT), or placebo!relugolix CT (placebo for 24 weeks followed by relugolix CT). The primary endpoints of the LTE study were the proportion of dysmenorrhea and NMPP responders at Week 52 and Week 104/end-of-treatment (EOT). A responder was a participant who achieved a predefined, clinically meaningful reduction from baseline in Numerical Rating Scale (NRS) scores (0 1/4 no pain, 10 1/4 worst pain imaginable) for the specific pain type with no increase in analgesic use. The predefined clinically meaningful threshold for dysmenorrhea was 2.8 points and for NMPP was 2.1 points. Secondary efficacy endpoints included change from baseline in Endometriosis Health Profile-30 (EHP-30) pain domain scores, a measure of the effects of endometriosis-associated pain on daily activities (function), NRS scores for dysmenorrhea, NMPP, dyspareunia, and overall pelvic pain, and analgesic/opioid use. Safety endpoints included adverse events and changes in BMD. MAIN RESULTS AND THE ROLE OF CHANCE: Of 1261 randomized patients, 1044 completed the pivotal studies, 802 enrolled in the LTE, 681 completed 52 weeks of treatment, and 501 completed 104 weeks of treatment. Demographics and baseline characteristics of the extension population were consistent with those of the original randomized population. Among patients randomized to relugolix CT at pivotal study baseline who continued in the LTE (N 1/4 277), sustained improvements in endometriosis-associated pain were demonstrated through 104 weeks. The proportion of responders at Week 104/EOT for dysmenorrhea and NMPP was 84.8% and 75.8%, respectively. Decreases in dyspareunia and improvement in function assessed by EHP-30 pain domain were also sustained over 2 years. At Week 104/EOT, 91% of patients were opioid-free and 75% of patients were analgesic-free. Relugolix CT over 104 weeks was well tolerated with a safety profile consistent with that observed over the first 24 weeks. After initial least squares mean BMD loss <1% at Week 24, BMD plateaued at Week 36 and was sustained for the duration of 104 weeks of treatment. Efficacy and safety results were generally consistent in women i the placebo!relugolix CT and delayed relugolix CT groups. LIMITATIONS, REASONS FOR CAUTION: The study was conducted as an open-label study without a control group over the 80 weeks of the extension period. Of the 802 patients who were enrolled in this LTE study, 681 patients (84.9%) and 501 patients (62.5%) of patients completed 52 and 104 weeks of treatment, respectively. In addition, there currently are no comparative data to other hormonal medications. Finally, a third (37.4%) of the study population terminated participation early. WIDER IMPLICATIONS OF THE FINDINGS: In conclusion, relugolix CT offers an additional option to help address an important unmet clinical need for effective, safe, and well-tolerated medical treatments for endometriosis that can be used longer-term, reducing the need for opioids and improving quality of life. The findings from this study may help support the care of women with endometriosis seeking longer-term effective medical management of their symptoms. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Myovant Sciences GmbH (now Sumitomo Pharma Switzerland GmbH). C.M.B. reports fees from Myovant, grants from Bayer Healthcare, fees from ObsEva, and Chair of ESHRE Endometriosis Guideline Group (all funds went to the University of Oxford); N.P.J. reports personal fees from Myovant Sciences, during the conduct of the study, personal fees from Guerbet, personal fees from Organon, personal fees from Roche Diagnostics; S.A.-S. reports personal fees from Myovant Sciences, personal fees from Bayer, personal fees from Abbvie, personal fees from UpToDate; J.S.P., and R.B.W. are employees and shareholders of Myovant Sciences; J.C.A.F. and S.J.I. are shareholders of Myovant Sciences (but at time of publicaion are no longer employess of Myovant Sciences); M.S.A. and K.W. have no conflicts to declare; V.M. is a consultant to Myovant; L.C.G. reports personal fees from Myovant Sciences, Inc and Bayer. The authors did not receive compensation for manuscript writing, review, and revision.Copyright © 2024 Oxford University Press. All rights reserved.

Becker, C. M., et al. (2021). "The Effect of Time Since Surgical Diagnosis of Endometriosis on Treatment Outcomes with Relugolix Combination Therapy: spirit Program." Journal of Minimally Invasive Gynecology 28(11): S11.
	Study Objective: To assess efficacy of relugolix combination therapy (Relugolix‐CT) in women who were surgically diagnosed with endometriosis <5 years and ≥5 years ago. Design: SPIRIT 1/2 were 24‐week randomized, double‐blind, placebo‐controlled Phase 3 studies. Setting: 124 (SPIRIT 1) and 95 (SPIRIT 2) clinical research centers globally. Patients or Participants: Premenopausal women (age 18–50 years) with surgically diagnosed endometriosis, moderate‐to‐severe dysmenorrhea and non‐menstrual pelvic pain (NMPP). Interventions: Once‐daily Relugolix‐CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) or placebo. Measurements and Main Results: Change in dysmenorrhea/NMPP NRS scores and Endometriosis Health Profile‐30 (EHP‐30) pain domain scores analyzed in women with endometriosis diagnosis <5 years (N=579) and ≥5 years (N=255) ago. Baseline demographics/clinical characteristics were comparable between subgroups. Mean (standard deviation) time since surgical diagnosis for Relugolix‐CT and for placebo: 2.1 (1.5) and 2.1 (1.5) years (<5‐years subgroup); 8.0 (2.8) and 7.8 (2.3) years (≥5‐years subgroup), respectively. With Relugolix‐CT, mean dysmenorrhea NRS and EHP‐30 pain domain score decreased significantly (both subgroups) vs placebo; mean NMPP NRS score decreased significantly in the <5‐years subgroup (Table). Conclusion: Relugolix‐CT reduced dysmenorrhea and improved daily functioning in both groups: surgical diagnosis <5 years and ≥5 years ago. Reduction in NMPP was statistically significant in women with surgical diagnosis <5 years ago.

Beckmann Matthias, W., et al. (2022). "Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy." Geburtshilfe und Frauenheilkunde 82(2): 139-180.
	Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.; Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all the authors are listed in the long German-language version of the guideline report./Die Interessenkonflikte der Autoren sind im Leitlinienreport aufgelistet. (Thieme. All rights reserved.)

Beckmann Matthias, W., et al. (2021). "The Diagnosis, Treatment, and Aftercare of Cervical Carcinoma." Deutsches Arzteblatt international 118(47): 806-812.
	Background: Approximately 4380 cases of cervical carcinoma were diagnosed in Germany in 2016. In women who had not participated in early detection programs, cervical carcinoma was usually already in an advanced stage at the time of diagnosis. Certified structures for care in conformity with the existing guidelines are available.; Methods: The new German clinical practice guideline was revised with the participation of 50 medical societies under the expert guidance of the Guideline Program in Oncology, which includes the German Association of the Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). A systematic literature review was conducted. Systematic reviews, meta-analyses, and randomized controlled trials (RCTs) were considered.; Results: The histologic tumor stage and lymph-node stage are essential determinants of the treatment strategy. The main innovation regarding surgical treatment is the revival of open hysterectomy (overall survival [minimally invasive vs open hysterectomy]: 94.04% vs 99.4%; hazard ratio [HR]: 6.00; 95% confidence interval [1.77; 20.30]). In addition, for tumors measuring 2 cm or less, sentinel node biopsy is recommended rather than radical pelvic lymphadenectomy. MRI-guided brachytherapy is an oblig atory component of radiochemotherapy (overall survival [radiochemotherapy with vs without brachytherapy]: 58.2% vs 46.2%, p<0.001). The standard palliative treatment consists of bevacizumab combined with a platinum-containing agent (overall survival: HR: 0.77 [0.62; 0.95]; p = 0.007).; Conclusion: Despite the introduction of new treatments, the outcome of patients with advanced cervical carcinoma has not much improved. In the surgical treatment of cervical carcinoma, the open approach is now favored. The sentinel node biopsy technique has become well established for the surgical staging of small tumors. Controlled trials are needed so that the outcome of women with cervical carcinoma, particularly in its advanced and metastatic stages, can be improved.

Becky, M., et al. (2022). "Interventions following a stillbirth, second trimester miscarriage or recurrent miscarriage to improve a women&#39;s health and subsequent pregnancy outcomes."
	
Bednar, E. M., et al. (2023). "Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems." Gynecologic Oncology 172: 106-114.
	Objective: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). Method(s): QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. Result(s): For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. Conclusion(s): A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.Copyright © 2023 Elsevier Inc.

Bednarikova, M., et al. (2022). "Can Schlafen 11 Help to Stratify Ovarian Cancer Patients Treated with DNA-Damaging Agents?" Cancers 14(10): 2353.
	Platinum-based chemotherapy has been the cornerstone of systemic treatment in ovarian cancer. Since no validated molecular predictive markers have been identified yet, the response to platinum-based chemotherapy has been evaluated clinically, based on platinum-free interval. The new promising marker Schlafen 11 seems to correlate with sensitivity or resistance to DNA-damaging agents, including platinum compounds or PARP inhibitors in various types of cancer. We provide background information about the function of Schlafen 11, its evaluation in tumor tissue, and its prevalence in ovarian cancer. We discuss the current evidence of the correlation of Schlafen 11 expression in ovarian cancer with treatment outcomes and the potential use of Schlafen 11 as the key predictive and prognostic marker that could help to better stratify ovarian cancer patients treated with platinum-based chemotherapy or PARP inhibitors. We also provide perspectives on future directions in the research on this promising marker.Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Beebeejaun, Y., et al. (2022). "Mode of conception and pregnancy outcomes: systematic review and meta-analysis of 110 studies and 33,655,021 singleton pregnancies." Human Reproduction 37(Supplement 1): i558-i559.
	Study question: Does mode of conception such as in-vitro fertilisation (IVF), ovulation induction (OI), intra-uterine insemination (IUI) affect singleton pregnancy outcomes when compared to spontaneous conception (SC)? Summary answer: Singleton pregnancies resulting from OI, IUI, IVF are associated with higher risks of adverse pregnancy outcomes compared to spontaneous pregnancies. What is known already: Several meta-analysis have shown singleton pregnancies resulting from IVF have adverse pregnancy outcomes However, these studies had much smaller sample size and did not compare OI or IUI to SC. Additionally, when matched studies were analysed, the pooled events used were not adjust for medical conditions such as polycystic ovaries (PCO) and chronic hypertension which predispose patients to gestational diabetes(GDM) and pre-eclampsia (PET).he lack of consensus on how PET and GDM was defined was also a cause of bias. Our study is the largest meta-analysis to date and aims to provide clinician with the latest evidence when offering fertility treatment. Study design, size, duration: Literature search in MEDLINE, COCHRANE Library, and Scopus was performed, up to November 2021. Randomised controlled trials (RCTs), non-randomised studies, cohort and case control studies, reporting on any association between pregnancy outcome, such as pre-eclampsia (PET), gestational diabetes mellitus (GDM), preterm birth, (<37 weeks (TB), very preterm birth , (<32 weeks (vVPTB), low birthweight (<2500g,LBW), very low birth weight (<1500g,VLBW) and small gestational age (SGA) in relation to mode of conception were included. Participants/materials, setting, methods: 110 studies consisting of 31 cohort studies and 79 case control were included comprising a total of 32,463,058spontaneous singleton conception compared to 1,191,963 singleton pregnancies following OI, IUI and IVF treatment .Matching criteria used for adjustment were also identified For PET and GDM, only studies which defined the condition according to international agreed consensus were included Any inconsistency between studies was quantified through Higgins' Chi-square (Chi2) and I-squared (I2) using statistical software R. Main results and the role of chance: Singleton pregnancies following, OI, IUI, or IVF had a higher odds of PET compared to SC (odds ratio [OR]1.95,, 95% confidence interval [CI]1.61-2.31; I2=97%), OR 1.53, 95%CI 1.36 -1.71,, I2=84% and OR1.62, 95%CI 0.94-2.78, I2=11%).respectively. For GDM, pregnancies following, OI, IUI, or IVF had a higher odds compared to SC (OR1.59, 95%CI 1.59 -1.71, I2=83%, OR 1.62, 95%CI 0.94-2.78, I2=11% and OR1.72, 95% CI 1.49-1.98; I2=13%). Higher odds of TB and vPTB were seen in pregnancies following OI and IVF compared to SC (PTB: OR1.80, 95% CI 1.76-1.85; I2=94% and , (OR 1.47, 95% CI 1.22-1.77 I2=66% and vPTB OR 2.92, 95% CI 2.76-3.09; I2=91%). Only one study reported PTB when comparing IUI to SC (OR 1.88, 95% CI 1.40-2.53) and comparing vPTB in OI vs SC (OR 1.73 95% CI 0.71-4.18). Singleton pregnancies following, OI or IVF had a higher odds of LBW and vLBW compared to SC (OR1.98, 95% CI 1.93-2.04; I2=96%),OR1.72, 95% CI 1.49-1.98 I2=13% and OR4.57, 95% CI 4.34-4.81; I2=98% and OR2.32, 95% CI 1.60-3.37; I2=56% respectively. The rate of SGA was comparable in IVF (OR 0.91, 95% CI 0.90-0.93; I2=99%), OI (OR 0.96, 95% CI 0.95-0.97; I2=100%) and IUI (RR 0.92, 95% CI 0.90-0.94; I2=31%). Limitations, reasons for caution: In cases of PE and GDM, published definitions differed in various studies and there was limited information given past medical history which increase the risk of such conditions. This made it impossible to separate the baseline confounders which may increase the risk of PE and consequently PTB, SGA and LBW. Wider implications of the findings: Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of adverse pregnancy outcomes. This is the largest systematic review to date analysing pregnancy outcomes and mode of conception comparing OI, IUI and IVF respectively. It provides the latest evidence possi le for clinicians to choose the safest fertility treatment.

Beelen, P., et al. (2021). "Predictive factors for failure of the levonorgestrel releasing intrauterine system in women with heavy menstrual bleeding." BMC Women's Health 21(1): 57.
	BACKGROUND: This study was conducted to identify factors that are associated with failure of treatment using the levonorgestrel releasing intrauterine system (LNG-IUS) in women with heavy menstrual bleeding. METHODS: For this study, data of a cohort of women treated with an LNG-IUS was used. Women who suffered from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future child wish, were recruited in hospitals and general practices in the Netherlands. Eight potential prognostic baseline variables (age, body mass index, caesarean section, vaginal delivery, previous treatment, anticoagulant use, dysmenorrhea, and pictorial blood assessment score) were analyzed using univariable and multivariable regression models to estimate the risk of failure. The main outcome measure was discontinuation of the LNG-IUS within 24 months of follow up, defined as removal of the LNG-IUS or receiving an additional intervention. RESULTS: A total of 209 women received the LNG-IUS, 201 women were included in the analyses. 93 women (46%) discontinued LNG-IUS treatment within 24 months. Multivariable analysis showed younger age (age below 45) (adjusted RR 1.51, 95% CI 1.10-2.09, p = .012) and severe dysmenorrhea (adjusted RR 1.36, 95% CI 1.01-1.82, p = .041) to be associated with a higher risk of discontinuation. CONCLUSIONS: High discontinuation rates are found in women who receive an LNG-IUS to treat heavy menstrual bleeding. A younger age and severe dysmenorrhea are found to be risk factors for discontinuation of LNG-IUS treatment. These results are relevant for counselling women with heavy menstrual bleeding.

Beelen, P., et al. (2021). "Treatment of women with heavy menstrual bleeding: Results of a prospective cohort study alongside a randomised controlled trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 257: 1-5.
	OBJECTIVE: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT. STUDY DESIGN: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands. Women suffering from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future fertility desire, were eligible for this trial. Women who declined randomisation were asked to participate in the observational cohort. The outcome measure was reintervention rate at 24 months of follow-up. RESULTS: 276 women were followed in the observational cohort of which 87 women preferred an initial treatment with LNG-IUS and 189 women preferred an initial treatment with endometrial ablation. At 24 months of follow-up women in the LNG-IUS-group were more likely to receive a reintervention compared to the women in the ablation group, 28/81 (35 %) versus 25/178 (14 %) (aRR 2.42, CI 1.47-3.98, p-value 0.001). No differences in reintervention rates were found between women in the observational cohort and women in the RCT. CONCLUSIONS: Women who receive an LNG-IUS are more likely to undergo an additional intervention compared to women who receive endometrial ablation. Reintervention rates of women in the cohort and RCT population were comparable. The results of this study endorse the findings of the RCT and will contribute to shared decision making in women with heavy menstrual bleeding.

Beesley Vanessa, L., et al. (2019). "A systematic literature review of trials of survivorship interventions for women with gynaecological cancer and their caregivers." European journal of cancer care 28(3): e13057.
	Core components of survivorship care include treatment of late and long-term effects, care coordination, promotion of psychological well-being, health and addressing special populations' needs. Women affected by gynaecological cancer and their caregivers can experience disease-specific issues. This review presents an overview of survivorship interventions that have been trialled among this population. Databases were searched in October/November 2016 to identify eligible studies. Titles, abstracts then full-text were assessed for inclusion by two reviewers until consensus was reached. Data were abstracted using standard tables. Study quality was independently appraised. Twenty-eight articles were included (five reviews; 23 trials). In regards to late and long-term treatment effects, our review found mounting high-level evidence for the effectiveness of psycho-educational programmes to improve physical aspects of sexual function and for exercise interventions for reducing fatigue. We also found emerging evidence for nurse-led follow-up care to improve care coordination and cognitive behavioural therapy to improve psychological wellbeing. There were gaps in the evidence for interventions to effectively address psychosexual issues specific to gynaecological cancer and needs of caregivers. Further research is required to explore strategies to improving psychosexual concerns after gynaecological cancer and the dynamics and supportive care needs of the patient-partner dyad. (© 2019 John Wiley & Sons Ltd.)

Begic, M., et al. (2023). "Comparison of Kegel exercises and a combination of Kegel exercises with the use of the KegelSmart biofeedback device in the treatment of static urinary incontinence." Medicinski Glasnik 20(2): 276-281.
	Aim To determine which of the two methods, Kegel exercises or combination of Kegel exercises with the use of the KegelSmart biofeedback device, has better therapeutic effects on the symptoms of SUI in females. Methods Fifty female patients with SUI were randomly divided into two groups: 25 treated with Kegel exercises, and 25 with the combination of Kegel exercises with the use of the KegelSmart biofeedback device. Patients in both groups performed Kegel exercises 30 minutes daily for 30 days. Patients in the second group, in addition to Kegel exercises, applied the KegelSmart device intra-vaginally for 20 minutes daily for 30 days. All patients filled out a questionnaire based on 12 questions consisting of an objective and a subjective component. Results The basic characteristics of the patients from both groups were not statistically significantly different: age 55.16 vs 54.52 years; number of births 1.80 vs 1.96; body mass index 29.12 vs 28.40. There was a statistically significant reduction in the values of all analysed objective and subjective parameters in the group treated with combination of Kegel exercises with the use of the Ke-gelSmart biofeedback device compared to Kegel exercises group. Conclusion Combination of Kegel exercises with the use of the KegelSmart biofeedback device has better therapeutic effects than Kegel exercises on the objective and subjective symptoms of SUI.Copyright © 2023, Medical Association of Zenica-Doboj Canton. All rights reserved.

Begovich, E., et al. (2021). "Endometriosis-associated cancer: Modern aspects of etiopathogenesis, treatment and rehabilitation." Obstetrics, Gynecology and Reproduction 15(3): 287-294.
	Aim: to analyze current literature sources on endometriosis-associated cancer (IEAS) in gynecology. Materials and Methods. We searched for publications in the international scientific databases: eLibrary, Google Scholar, ScienceDirect, Cochrane Library, PubMed/MEDLINE and clinical research registries. For this systematic analysis, only full-text publications were used. We evaluated the reliability of evidence and the methodological quality of the studies. The data on the modern approach to the therapy and rehabilitation of women with external genital endometriosis (EGE) are presented. Search terms for publications in Russian and English were used: <>, <>, <>, <>. Results. Despite the fact that EGE is considered a benign disease, there is a risk for its malignant transformation. However, the pathogenesis and pathomorphological mechanisms of IEAS are not yet fully understood. Conclusion. Active management of the rehabilitation period for women with EGE provides an opportunity for early diagnosing recurrences that will provide early diagnostics ovarian IEAS and improve the main indicators of the quality of life for such patients.Copyright © 2021 IRBIS LLC. All Rights Reserved.

Begovich, E., et al. (2022). "Assessing sexual dysfunction in patients with external genital endometriosis." Obstetrics, Gynecology and Reproduction 16(4): 354‐364.
	Introduction. External genital endometriosis (EGE) is a chronic, relapsing disease that affects various aspects of sexual function, the quality of sexual and interpersonal relationships, physical and psycho‐emotional health and leads to social maladjustment and anxiety‐depressive disorders, resulting in progressively decreased quality of life (QoL). Aim: to analyze an impact of sexual disorders on QoL of women with painful and painless EGEs. Materials and Methods. A prospective comparative randomized interventional study involved 160 patients (110 and 50 women with painful and painless EGE, respectively) of reproductive age, with laparoscopically and morphologically verified diagnosis according to the revised American Fertility Society scoring system (R‐AFS, 1996). Pain syndrome and sexual dysfunction were assessed using specialized questionnaires: visual analogue scale (VAS), PainDETECT, and Female Sexual Function Index (FSFI). After surgical treatment, 8 patients refused to participate in the study (6 with painful EGE and 2 with painless EGE). Thus, only 152 women passed all stages of the study. The patients were divided into 4 groups depending on the presence and/or absence of pain syndrome and the tactics of the rehabilitation period ("active" or "passive"): group IA consisted of 49 (47.1 %) women with pain and "active" rehabilitation; group IБ – 55 (52.9 %) women with pain syndrome and "passive" rehabilitation tactics; group IIA – 23 (47.9 %) patients without pain syndrome with "active" rehabilitation; group IIБ – 25 (52.1 %) patients without pain syndrome with "passive" rehabilitation tactics. Results. Women with painful vs. painless EGE were found to have a more severe course of the disease and a markedly decreased quality of sexual life. It was observed that patients with "active" rehabilitation tactics (groups IA and IIA) had intensity of the pain syndrome and the neuropathic pain component significantly decreased, improved parameters of the quality of sexual life, sexual desire and sexual excitability compared to patients with "passive" rehabilitation tactics applied with the measures within the framework of the National Clinical Guidelines (groups IБ and IIБ). Conclusion. A significantly decreased quality of sexual life of EGE patients indicates a need for assessing and correcting sexual disorders as well as introducing early onset of rehabilitation measures by using a multidisciplinary approach.

Behbehani, S., et al. (2019). "Mortality Rates in Laparoscopic and Robotic Gynecologic Oncology Surgery: A Systemic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 26(7): 1253.
	Objective: To review early operative mortality (<30 days) for minimally invasive surgery (MIS), laparoscopic and robotic, in gynecologic oncology.; Data Sources: An electronic-based search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Database in the last 10 years.; Methods of Study Selection: All MIS studies in gynecologic oncology reporting operative mortality from any cause (within 30 days) were included. Studies were excluded if mortality was not reported for MIS or included benign gynecology.; Tabulation, Integration, and Results: Meta-analysis was applied to calculate pooled mortality rates using the inverse-variance method. The relative risks and their corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. Sixty-five studies were included (39 183 patients) for an operative mortality of 1:381 (95% CI, 1:306-1:474). Studies were subselected and analyzed by procedures, malignancy, and surgical approach. Of 39 183 patients, 38 619 underwent any type of hysterectomy for a mortality of 1:379 (95% CI, 1:304-1:472). The mortality was 1:281 (95% CI, 1:169-1:469) for a laparoscopic approach and 1:476 (95% CI, 1:365-1:620) for a robotic approach. There were 3369 patients with early cervical cancer undergoing radical hysterectomy with a mortality of 1:2049 (95% CI, 1:356-1:11 832). There were 3501 patients with endometrial cancer undergoing hysterectomy with lymph node dissection with a mortality of 1:195 (95% CI, 1:109-1:349). There were 418 patients with ovarian cancer undergoing MIS procedures with a mortality of 1 in 685 (95% CI, 1:44-1:10971). Eleven studies with 4037 patients compared mortality of gynecologic oncology surgery of any type (laparoscopic [1:626] vs robotic [1:716] for a relative risk of 1.12 [95% CI, 0.35-3.49]).; Conclusion: The overall operative mortality for minimally invasive surgery in gynecologic oncology is 1 in 381 (95% CI, 1:306-1:474). For patients with early cervical cancer, it is 1:2049 (95% CI, 1:356-1: 11832), for endometrial cancer with node dissection it is 1:195 (95% CI, 1:109-1:349), and for ovarian cancer it is 1 in 685 (95% CI, 1:44-1:10 971). There is no difference between the type of MIS approach for patients undergoing any type of gynecologic oncology surgery. (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Behbehani, S., et al. (2022). "Pregnancy Rates after Surgical Resection of Deep Infiltrating Endometriosis in Patients with Infertility: A Systematic Review and Meta-Analysis." Journal of Gynecologic Surgery 38(1): 24-32.
	Objective: The aim of this review and meta-analysis was to assess spontaneous pregnancy rates after excision of deep infiltrating endometriosis (DIE) in patients with infertility. Material(s) and Method(s): An electronic-based search was performed on PubMed, Embase, Scopus, Web of Science, and the Cochrane Database from the last 10 years. All studies, including surgical resection of DIE (>5 mm depth confirmed on pathology) and pregnancy rates published in English, French, Spanish, and Italian during the last 10 years were reviewed. Studies with only ovarian involvement were excluded. A meta-analysis was performed to calculate pooled pregnancy rates, using a random-effects model with inverse-variance weighting. The 95% confidence intervals (95% CIs) for the pregnancy rates were calculated with Wilson Score with continuity correction (WSCC). Studies with extreme heterogeneity and influence were excluded. Result(s): Fourteen articles fit the inclusion criteria (for estimation of overall pregnancy rates) for a total of 587 patients with a mean age of 32.4 years (2 prospective studies and 12 retrospective studies). DIE locations included the intestinal and genitourinary tracts, and other nonvisceral locations. Infertility was defined as preoperative infertility of > 1 year. Overall pregnancy rate after surgical resection was 44.8% (95% CI: 39.7%-50.1%) with a 30% (95% CI: 25%-35.5%) spontaneous pregnancy rate. Live birth rate was 41.9% (95% CI 35.2%-48.9%). Conclusion(s): Resection of DIE improves pregnancy rates in patients with infertility. The spontaneous pregnancy rate after surgical resection is 30%. (J GYNECOL SURG 38:24)Copyright © 2022, Mary Ann Liebert, Inc., publishers.

Behery, M. A., et al. (2021). "Assisted Oocyte Activation in Recurrent Fertilization Failure." Journal of Reproductive Medicine 66(6): 371‐377.
	OBJECTIVE: Despite the high success rate of intracy‐toplasmic sperm injection (ICSI), total fertilization failure still occurs in up to 3% of all ICSI cycles and can recur in subsequent cycles, even when enough oocytes and motile spermatozoa are available. Several reports show that most couples suf‐fering from ICSI failure ben‐efit from the application of ICSI combined with assisted oocyte activation. A variety of artificial activating meth‐ods is used in human assisted reproduction treatment, including physical, mechan‐ical, or chemical stimuli, which provoke one or more calcium rises in the oocyte cytoplasm. STUDY DESIGN: Randomized controlled trial. Set‐ting: a university fertility center. Subjects: 150 infertile patients who underwent ICSI and all had a history of recurrent fertilization failure. The patients were randomly allocated into 2 equal groups. Group 1=75 patients who underwent ICSI without oocyte activa‐tion. Group 2=75 patients who underwent ICSI with oocyte activation. Reproductive outcomes were compared between both groups. RESULTS: There were significant differences between the groups regarding the number of oocytes retrieved, number of the mature oocytes, fertilization rate, and pregnancy rate. CONCLUSION: Assisted oocyte activation with calcium ionophore results in significant improvement in the fertilization, cleavage, and pregnancy rates after ICSI. (J Reprod Med 2021;66: 371–377).

Beinert, S. V., et al. (2021). "Effects of progesterone on vasomotor symptoms in postmenopausal women- an RPCDBT." Maturitas 152: 86-87.
	Introduction: In 2012, a Canadian study found significant reductions of hot flushes with a daily dose of 300mg progesterone in healthy, non-obese women. The PROGEST-study was designed to validate these results and to fulfill FDA-criteria for this indication. Methods and Participants: This prospective multi-center randomized, double-blind placebo-controlled trial studied 3 doses of progesterone (200 mg, 300 mg, 400 mg) against placebo for 12 weeks. After a one-week screening phase with diary-documentation of hot flushes, patients with >50 hot flushes in 7 days were randomized 1:1:1:1. Menopause Rating Scale and Pittsburgh Sleep Quality Index were documented 3 times per week, clinical and ultrasound parameters were recorded at screening and after 12 weeks. Result(s): 74 women were recruited, the full analysis set (FAS) comprised 54 subjects; 44 remained in the study as per protocol (PP);. Mean age was 56,5 yrs, and average BMI was 27,9; two thirds of the participants had co-morbidities, mostly hypertension (42,6%). The main result, namely the effect on the number of moderate to severe hot flushes between baseline and week 12 was - 7,4/d in the placebo-Arm, -7,7 VMS/d with 200 mg progesterone/day, -8,3 VMS/d on 300mg/d progesterone and -9,0/d on 400mg/d. The trial noted 32 treatment emergent adverse events (TEAE) in 18 participants. Most of these were minor AEs, one SAE involved the occurrence of a syncope requiring hospitalization on the day after the initiation of progesterone, which lead to discontinuation of the drug. Discussion(s): Baseline VMS frequency was higher in the German than in the Canadian study and the German placebo-group had a stronger decrease in VMS-frequency during the PROGEST-study (-7,4 VMS/d) than in the Canadian trial (-1,4 VMS/d). Study participants in Germany were older (56,5 yrs) than the Canadian women (age: 55,5 yrs under progesterone vs. 54,4 yrs. in the placebo group). Time since the final menstrual period in Canada averaged 3,9 years in the progesterone group and only 2,5 years in the placebo group. 94% vs. 98% of women in the Canadian study experienced natural menopause, only 3% vs 2% had a hysterectomy. This proportion was much higher in the German cohort. In Canada, CVD, smoking, BMI 35 or over, diabetes mellitus, hypertension or abnormal ECG, fasting lipids and glucose were exclusion criteria. In the PROGEST study, two thirds of the participants had any type of comorbidity, mainly (in 42,6%) hypertension.Copyright © 2021

Beishembaev, A. M., et al. (2022). "Ovarian carcinosarcoma (a literature review)." Obstetrics, Gynecology and Reproduction 16(5): 575-587.
	Introduction. Despite that ovarian carcinosarcoma (OCS) is an extremely rare disease, it is of great medical and social importance by taking into account very high level of overall mortality, recurrence, metastasis, and economic costs. Aim(s): to summarize current data on various aspects of OCS. Materials and Methods. The search strategy for English written papers published in databases PubMed/MEDLINE, Scopus, Web of Science, Google Scholar was based on the following keyword queries: <>, <>, <>, <>, <>, <>, <>. The search depth was limited within the years 2010-2022, by prioritizing the search depth within the last 5 years (2017-2022). Results. We found 48 articles in English, published from 2016 to 2022, of which 47 (97.9 %) articles were published within the last 5 years. Scientific data are represented by studies with a small patient sample and with low evidence base. The results of the analysis for identified publications showed a limited, fragmented and inconsistent scientific data both in terms of etiology, pathogenesis and treatment, as well as an impact of OCS stages, age and other risk factors on the likelihood of relapses. Conclusion. The lack of extensive clinical studies along with observed substantial number of controversial issues may be accounted for by OCS low prevalence and complex pathogenesis. Nevertheless, the results obtained during the generalization of scientific knowledge provide a realistic insight into the current state of global science about this medical and social disease and may be used to improve the diagnostics and treatment of OCS patients.Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

Bektas, H., et al. (2022). "Development and evaluation of the efficacy of a web-based education program among cancer patients undergoing treatment with systemic chemotherapy: a randomized controlled trial." Supportive Care in Cancer 30(7): 6021-6033.
	Purpose: The study aimed to develop a web-based education program among cancer patients undergoing treatment with systemic chemotherapy and to evaluate the efficacy of the program on symptom control, quality of life, self-efficacy, and depression. Method(s): A web-based education program was prepared in line with patient needs, evidence-based guidelines, and expert opinions and tested with 10 cancer patients. The single-blind, randomized controlled study was conducted at a medical oncology unit of a university hospital. Pretests were applied to 60 cancer patients undergoing treatment with systemic chemotherapy, and the patients (intervention: 30, control: 30) were randomized. The intervention group used a web-based education program for 3 months, and they were allowed to communicate with researchers 24/7 via the website. The efficacy of a web-based education program at baseline and after 12 weeks was evaluated. The CONSORT 2010 guideline was performed. Result(s): In the first phase results of the study, it was found that most of the patients with cancer wanted to receive education about symptom management and the side effects of the treatment. Expert opinions on the developed website were found to be compatible with each other (Kendall's Wa = 0.233, p = 0.008). According to the randomized controlled study results, patients who received web-based education reported significantly fewer symptoms (p = 0.026) and better quality of life (p = 0.001), but there was no statistically significant difference in the self-efficacy and depression levels during the 3-month follow-up period (p0.05). The most frequently visited links in the web-based education program by the patients with cancer were the management of chemotherapy-related symptoms (62.6%). Conclusion(s): A web-based education program was found to be efficacy in remote symptom management and improving the quality of life of cancer patients. Trial registration: www.clinicaltrials.gov, NCT05076916 (October 12, 2021, retrospectively registered).Copyright © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Belan, M., et al. (2021). "Cost-Effectiveness Analysis of an Interdisciplinary Lifestyle Intervention Targeting Women With Obesity and Infertility in Comparison to Usual Care."  5: A730.
	Although lifestyle modification is considered as the firstline treatment for women with obesity and infertility, these women generally do not have access to a program supporting them in adopting healthy habits that is integrated to fertility care. Implementing such a program requires to demonstrate its efficiency. The purpose of this study was to conduct a cost‐effectiveness analysis (CEA) of an interdisciplinary lifestyle intervention (Fit‐for‐Fertility (FFF) program) for women with obesity and infertility, in comparison with the usual care protocol, i.e. fertility treatments. Methods: A CEA was conducted alongside a randomized controlled trial, recruiting women at the fertility clinic of the Centre hospitalier universitaire de Sherbrooke. Women were randomized to: i) the intervention group (IG): FFF program alone for 6 months (individual follow‐ups every 6 weeks and 12 group sessions), and in combination with usual care for infertility after 6 months if not pregnant; or ii) control group (CG): usual care from the outset. Data were collected in both groups, during 18 months or until the end of the pregnancy for those who became pregnant. Costs related to the management of infertility, obesity, pregnancy and childbirth, and the FFF program were considered and collected by self‐reported questionnaires, review of medical records and administrative databases. Live birth (LB) rate was used to assess effectiveness. The CEA's parameter of interest was the incremental cost‐effectiveness ratio (ICER), calculated by non‐parametric bootstrap with 5,000 iterations. All costs are in Canadian dollars, 2019. Results: A total of 130 women were randomized (65 CG, 65 IG). We present results for the 108 women (57 CG, 51 IG) who completed at least 6 months in the study. We observed an absolute difference of 14.2% (p=0.328) in LB rate between groups (IG: 51.0%; CG: 36.8%). Total mean costs per patient were significantly higher in the IG vs the CG for healthcare system's ($5,660 ± $3,200 vs $3,631 ± $3,389; p=0.002) and society's ($9,745 ± $5,899 vs $6,898 ± 7,021; p=0.026) perspectives. We observed an ICER of $12,633 per additional LB [$5,319‐$19,947] from the healthcare system's perspective, and $5,980 [$3,086‐$8 874] from the patients' perspective. Overall, the ICER for the society's perspective, which includes both previous perspectives, was estimated at $24,393 per additional LB [$15,509‐ $33,276]. Conclusion: According to our results, a lifestyle intervention may be clinically more effective than the usual protocol of care for women with obesity and infertility, but generates higher costs as well, resulting in a positive ICER (of $12,600 per additional life birth for the healthcare system). Such an intervention could be considered efficient compared to the usual standard of care, but studies are needed to assess the willingness to pay of stakeholders for this type of intervention.

Belgium, B. V. A. C. (2021). Study Evaluating the Efficacy and Safety of Miconazole Nitrate + Domiphen Bromide Vaginal Cream in the Treatment of Subjects With Acute Vulvovaginal Candidiasis.
	No Results Available Drug: Miconazole Nitrate 2% + Domiphen Bromide Low Dose|Drug: Miconazole Nitrate 2% + Domiphen Bromide High Dose|Drug: Miconazole Nitrate 2% The proportion of subjects with clinical cure|The proportion of subjects with mycological eradication|The proportion of subjects with overall therapeutic success|Change from Baseline in vulvovaginitis symptom questionnaire total score|Change from Baseline in the EQ-5D questionnaire total score Female Phase 2 90 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment FHP-2021-2-26 October 2022

Bell, J. G., et al. (2022). "The impact of art therapy on anxiety and hope in patients with gynecologic cancer undergoing chemotherapy." Arts in Psychotherapy 80: 101947.
	Clinical research investigating the benefits of art therapy in individuals undergoing cancer treatment is growing, yet study designs focusing on certain cancers such as gynecologic malignancies are lacking. This study aimed to assess the impact of art therapy interventions on both anxiety and hope in patients with gynecologic cancer patients. The study design was prospective and non-randomized. Eligible patients had a primary or recurrent gynecologic malignancy, and were scheduled to receive at least six cycles of chemotherapy over eighteen weeks. Patients completed State Hope and State Anxiety questionnaires before and after each of five art therapy interventions during chemotherapy. Eighteen patients completed the study. Both anxiety and hope significantly improved after each art therapy session except for one. In addition, both anxiety and hope significantly improved between visit 1 and visit 5: State Hope -Visit 1 vs. Visit 5 (35.3 +/- 7.8 vs. 40.0 +/- 7.2), p = 0.019, effect size = 0.63; State Anxiety -Visit 1 vs. Visit 5 (32.8 +/- 9.3 vs. 27.8 +/- 8.8), p = 0.038, effect size = -0.53. The results showed art-based interventions facilitated by a board-certified art therapist positively impacted two domains in the quality of life of gynecologic cancer patients undergoing chemotherapy. The attitude of patients, namely, a willingness to accept art therapy, may influence the outcome of the interventions.Copyright © 2022 Elsevier Ltd

Bell, S., et al. (2023). "Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis." International Journal of Gynecological Cancer 33(12): 1875-1881.
	Objective To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. Methods All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. Results Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was >=4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. Conclusions In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.Copyright © 2023 BMJ Publishing Group. All rights reserved.

Bellanti, D. M., et al. (2022). "Rapid Review on the Effectiveness of Telehealth Interventions for the Treatment of Behavioral Health Disorders." Military medicine 187(5-6): e577-e588.
	INTRODUCTION: The Psychological Health Center of Excellence conducted a rapid review of the literature to investigate the effectiveness of behavioral health treatments (i.e., evidence-based psychotherapy and psychiatry) delivered in person compared to telehealth (TH; i.e., video teleconference and telephone). MATERIALS AND METHODS: The rapid review methods included a systematic search of a single database (PubMed), hand-searching of relevant systematic reviews, dual screening, single-person data abstraction verified by a second person, and dual risk of bias assessment. Due to heterogeneity across studies, no quantitative analyses were conducted. RESULTS: Twenty-two randomized controlled trials (RCTs), eight of which were non-inferiority trials, evaluated the effectiveness of TH via telephone or video teleconferencing compared to in-person (IP) delivery for patient populations with posttraumatic stress disorder, depression, and mixed diagnoses. The majority of RCTs and all but one of the eight non-inferiority trials found that clinical outcomes did not differ between TH and IP treatment delivery. Two studies found that subgroups with higher symptom severity (hopelessness and anxiety disorders, respectively) in the TH group had worse treatment-related outcomes than IP participants with similar symptom profiles. The majority of studies found no significant differences in satisfaction with care, quality of the therapeutic alliance, or study discontinuation between TH and IP groups. CONCLUSION: Based on evidence from 22 RCTs, the use of TH platforms, including video conference and telephone modalities, generally produces similar outcomes as face-to-face provision of psychotherapy and psychiatry services.

Bellone, S., et al. (2021). "A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793)." Annals of oncology : official journal of the European Society for Medical Oncology 32(8): 1045‐1046.
	
Ben-Arye, E., et al. (2023). "Acupuncture and integrative oncology for taxane-induced peripheral neuropathy: a randomized multicentered study." International Journal of Gynecological Cancer 33(5): 792-801.
	Objective To compare the effectiveness of acupuncture alone or with additional integrative oncology modalities for taxane-induced peripheral neuropathy-related symptoms in patients with gynecological and breast cancer. Methods The study was a prospective evaluation of patients undergoing twice-weekly treatments with either acupuncture alone (single-modality, group A) or with additional manual-movement and mind-body therapies (multimodality, group B), for 6 weeks. Symptom severity was assessed at baseline, 6 weeks, and 9 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool; and von Frey perception thresholds. Additional symptoms were also assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Measure Yourself Concerns and Wellbeing (MYCaW) study tool. Results For the 120 participants (60 in each study arm), baseline to 6-week scores were similar in both groups for improved FACT-Tax physical wellbeing and scores for hand numbness/tingling; EORTC physical functioning and global health status; and MYCaW scores. FACT-Tax taxane subscales and scores for foot numbness/tingling improved only in group A (p=0.038), while emotional wellbeing FACT-Tax (p=0.02) and EORTC pain (p=0.005) improved only in group B. Group B showed greater improvement for FACT-Tax neuropathy-related concerns than group A at 24 hours (p=0.043) and 7 days (p=0.009) after the first treatment. Conclusion Acupuncture alone or with additional integrative oncology modalities may help reduce neuropathy-related symptoms. The single-modality group demonstrated greater improvement for foot numbness/tingling, and the multimodality group demonstrated improvement for pain and improved emotional wellbeing and neuropathy-related concerns in the first week of treatment. Trial registration number NCT03290976.Copyright © 2023 BMJ Publishing Group. All rights reserved.

Ben-Arye, E., et al. (2022). "Impact of acupuncture and integrative therapies on chemotherapy-induced peripheral neuropathy: A multicentered, randomized controlled trial." Cancer 128(20): 3641-3652.
	Background: To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QoL) in oncology patients. Method(s): In this prospective, pragmatic, and patient-preference study, patients with CIPN were treated with acupuncture and CIM therapies (intervention group) or standard care alone (controls) for 6 weeks. Patients in the intervention arm were randomized to twice-weekly acupuncture-only (group A) or acupuncture with additional manual-movement or mind-body CIM therapies (group B). Severity of CIPN was assessed at baseline and at 6 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool. Other QoL-related outcomes were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC); and the Measure Yourself Concerns and Well-being questionnaire. Von Frey measurements examined perception thresholds. Result(s): Of 168 participants, 136 underwent the study intervention (group A, 69; group B, 67), with 32 controls. Baseline-to-6-week assessment scores improved significantly in the intervention arm (vs controls) on FACT-Tax (p =.038) and emotional well-being (p =.04) scores; FACT-TAX scores for hand numbness/tingling (p =.007) and discomfort (p <.0001); and EORTC physical functioning (p =.045). Intervention groups A and B showed improved FACT-Tax physical well-being (p <.001), FACT-TAX total score (p <.001), FACT-TAX feet discomfort (p =.003), and EORTC pain (p =.017) scores. Conclusion(s): Acupuncture, with or without CIM modalities, can relieve CIPN-related symptoms during oncology treatment. This is most pronounced for hand numbness, tingling, pain, discomfort, and for physical functioning.Copyright © 2022 American Cancer Society.

Ben-Arye, E., et al. (2023). "A randomized-controlled trial assessing the effect of intraoperative acupuncture on anesthesia-related parameters during gynecological oncology surgery." Journal of Cancer Research and Clinical Oncology 149(11): 8177-8189.
	Context and objectives: The present study examined the impact of intraoperative acupuncture on anesthesia-related parameters in patients undergoing gynecological oncology surgery. Method(s): Participants underwent preoperative integrative oncology (IO) touch/relaxation treatments, followed by intraoperative acupuncture (Group A); preoperative IO treatments without acupuncture (Group B); or standard care only (Group C). Mean arterial pressure (MAP), heart rate (HR), MAP variability (mean of MAP standard deviation), bispectral index (BIS), and calculated blood pressure Average Real Variability (ARV) were measured intraoperatively. Result(s): A total of 91 patients participated: Group A, 41; Group B, 24; Group C, 26. Among patients undergoing open laparotomy, Group A showed lower and more stable MAP and HR compared to Group B, (MAP, p = 0.026; HR, p = 0.029) and Group C (MAP, p = 0.025). Mean BIS, from incision to suture closing, was lower in Group A (vs. controls, p = 0.024). In patients undergoing laparoscopic surgery, MAP was elevated within Group A (p = 0.026) throughout surgery, with MAP variability significantly higher in Group A (P = 0.023) and Group B (P = 0.013) 10 min post-incision (vs. pre-incision). All groups showed similar intraoperative and post-anesthesia use of analgesic medication. Conclusion(s): Intraoperative acupuncture was shown to reduce and stabilize MAP and HR, and reduce BIS in gynecology oncology patients undergoing laparotomy, with no impact on perioperative analgesic medication use. In the laparoscopic setting, intraoperative acupuncture was associated with elevated MAP. Further research is needed to explore the hemodynamic and BIS-associated benefits and risks of intraoperative acupuncture, and the impact on the use of analgesic drugs in response to these changes.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Ben-Arye, E., et al. (2022). "Can integrative oncology increase adherence to chemotherapy in advanced gynecologic cancer?" Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30(5): 4345-4354.
	Objective: Integrative oncology (IO) has been shown to improve quality-of-life (QoL) and increase adherence to planned chemotherapy regimens. This study examined the impact of a patient-tailored IO program on adherence to chemotherapy among patients with advanced gynecological cancer.; Methods: This prospective non-randomized, pragmatic, preference study examined patients with stage III/IV gynecological cancers undergoing 6 weeks of weekly IO treatments. Adherence to the planned chemotherapy regimen was assessed using the relative dose intensity (RDI) calculation. Patients consistently attending IO treatments (consistent-IO group) were compared to those who were not (non-consistent IO group).; Results: RDI was calculated for 73 patients in the consistent-IO group (99 chemotherapy cycles) and 61 in the non-consistent-IO group (96 cycles with IO care, 126 cycles without). Both groups had similar baseline demographic characteristics, with endometrial cancer more prevalent in the consistent-IO group. RDI was significantly less reduced in the consistent-IO chemotherapy group (p = 0.005). During taxane-based regimens, RDI was better maintained in the consistent-IO group (0.93 vs. 0.87, p = 0.012), though not with platinum-based cycles. Linear regression model found a correlation between preserved RDI and consistent attendance at weekly IO treatments, and lower rates of chemotherapy-induced peripheral neuropathy and pain.; Conclusion: Patient-tailored IO programs for patients with advanced gynecological cancer may help preserve adherence to chemotherapy at 6 weeks, especially with taxane-based regimens. Further research needs to explore whether this correlation is chemotherapy agent-specific. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Benbrook Doris, M., et al. (2023). "Association of Sialyl Tn antigen with cervical cancer lymph node status: An NRG oncology/GOG study." Gynecologic Oncology 171: 67-75.
	Objective: Detection of lymph node metastases in cervical cancer patients is important for guiding treatment decisions, however accuracies of current detection methods are limited. We evaluated associations of abnormal glycosylation, represented by Tn and STn antigens on mucin (MUC) proteins, in primary tumor specimens with lymph node metastasis or recurrence of cervical cancer patients.; Methods: Surgical specimens were prospectively collected from 139 patients with locally-advanced cervical cancer undergoing lymphadenectomy enrolled in a nation-wide clinical trial (NCT00460356). Of these patients, 133 had primary cervix tumor, 67 had pelvic lymph node (PLN) and 28 had para-aortic lymph node (PALN) specimens. Fixed tissue serial sections were immunohistochemically stained for Tn, STn, MUC1 or MUC4. Neuraminidase was used to validate Tn versus STn antibody specificity. Stain scores were compared with clinical characteristics.; Results: Primary tumor STn expression above the median was associated with negative PLN status (p-value: 0.0387; odds ratio 0.439, 95% CI: 0.206 to 0.935). PLN had higher STn compared to primary tumor, while primary tumor had higher MUC1 compared to PALN, and MUC4 compared to PALN or PLN (p = 0.017, p = 0.011, p = 0.016 and p < 0.001, respectively). Tn and STn expression correlated in primary tumor, PALN, and PLN, Tn and MUC1 expression correlated in primary tumors only (Spearman correlation coefficient [r] = 0.301, r = 0.686, r = 0.603 and r = 0.249, respectively).; Conclusions: STn antigen expression in primary cervical tumors is a candidate biomarker for guiding treatment decisions and for mechanistic involvement in PLN metastases.; Competing Interests: Declaration of Competing Interest Dr. Wei Deng, Dr. Christopher West, Dr. Rajani Rai, Dr. Rachel Conrad, Mrs. Hanke van der Wel, Dr. Sanam Husain, Dr. Mae Zakhour, Dr. Amanda Jackson and Dr. Doris Benbrook have no conflicts of interest to disclose. Dr. Michael Gold reports receiving honoraria from ASCCP as well as serving as a past member of the Board as well as serving as Secretary, Treasurer, Vice-President, and President for ASCCP. Dr. Moore reports personal fees and other from Astra Zeneca, grants, personal fees and other from Genentech/Roche, grants, personal fees and other from Immunogen, grants, personal fees and other from GSK/Tesaro, other from Pfizer, personal fees from Aravive, personal fees from VBL Therapeutics, personal fees and other from Onco Med, grants and other from Lilly, personal fees from Eisai, personal fees from Vavotar, personal fees from Abbvie, personal fees from Tarveda, personal fees from Myriad, personal fees from Rubius, personal fees from Elevar, personal fees from Merck, personal fees from Mersana, personal fees from Sorrento, personal fees from OncXerna, personal fees from Alkemeres, personal fees from blueprint pharmaceuticals, personal fees from Mereo, personal fees from IMab, outside the submitted work; and serves as the Associate Director for GOG Partners and a GOG Foundation Board of Directors member. Dr. Nick Spirtos would like to disclose receiving research funding to his Institution from AbbVie, AstraZeneca, Genentech/Roche, Clovis Oncology, and Seattle Genetics. With regard to Patents, Royalties, and Other Intellectual Property, Dr. Spirtos wishes to disclose Application No. PCT/US 2019/19465 Cannabis based therapeutic and method of use Application No. Title Country Status Filed Date Application No. Patent Ref. No.199236–701,611/EP Title: CANNABIS BASED THERAPEUTIC AND METHOD OF USE Country: European Patent Status: Published 2/25/2019 19,710,540.6 Patent Ref. No.199236–701,691/PCT-BR Title: CANNABIS BASED THERAPEUTIC AND METHOD OF USE Country Brazil Status: Application 2/25/2019 1,120,200,170,232 Patent Ref. No.199236–701,831/PCT-US Title: CANNABIS BASED THERAPEUTIC AND METHOD OF USE Country United States of America Status: Published 2/25/2019 16/971,781 Patent Ref. No.199236–701,891/HK Title: CANNABIS BASED THERAPEUTIC AND METHOD OF USE Country Hong Kong Status: Published 6 25/2021 62,021,033,676.9 Patent Ref. No. Title Country Status Filed Date Application No. Patent Ref. No.199237–701,601/PCT Title: COMPOSITIONS COMPRISING CANNABIDIOL AND FLAVANONES Country: Patent Cooperation Treaty Status: Application 7/1/2021 PCT/US21/40115 Patent Ref. No.199237–701,691/BR Title: COMPOSITIONS COMPRISING CANNABIDIOL AND FLAVANONES Country: Brazil Status: Application 11/19/2020 1,020,200,236,644 Patent Ref. No.199237–7,019,761/UY Title: COMPOSITIONS COMPRISING AND FLAVANONES Country: Uruguay Status: Application 11/20/2020 38,965. Dr. Cara Mathews reports receiving funding from the NCI to her institution. Dr. Mathews also reports funding from Syros, Decophera, Astellas Pharma, Tesaro/GSK, Seattle Genetics, Regeneron, Moderna, Laekna Therapeutics, outside of the submitted work. In addition, Dr. Mathews reports receiving support from GSK and Seattle Genetics to attend investigator meetings and served on an Advisory Board for IMAB Biopharma. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bender, A., et al. (2023). "ESHRE guideline: recurrent pregnancy loss: an update in 2022." Human Reproduction Open 2023(1): hoad002.
	Study Question: What are the updates for the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature from 2017 to 2022?; Summary Answer: The guideline development group (GDG) updated 11 existing recommendations on investigations and treatments for RPL, and how care should be organized, and added one new recommendation on adenomyosis investigation in women with RPL.; What Is Known Already: A previous ESHRE guideline on RPL was published in 2017 and needs to be updated.; Study Design Size Duration: The guideline was developed and updated according to the structured methodology for development and update of ESHRE guidelines. The literature searches were updated, and assessments of relevant new evidence were performed. Relevant papers published between 31 March 2017 and 28 February 2022 and written in English were included. Cumulative live birth rate, live birth rate, and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes.; Participants/materials Setting Methods: Based on the collected evidence, recommendations were updated and discussed until consensus was reached within the GDG. A stakeholder review was organized after the updated draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee.; Main Results and the Role of Chance: The new version of the guideline provides 39 recommendations on risk factors, prevention, and investigation in couples with RPL, and 38 recommendations on treatments. These includes 62 evidence-based recommendations-of which 33 were formulated as strong recommendations and 29 as conditional-and 15 good practice points. Of the evidence-based recommendations, 12 (19.4%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (34 recommendations; 54.8%), or very low-quality evidence (16 recommendations; 25.8%). Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions those investigations and treatments that should not be used for couples with RPL.; Limitations Reasons for Caution: The guidelines have been updated; however, several investigations and treatments currently offered to couples with RPL have not been well studied; for most of these investigations and treatments, a recommendation against using the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.; Wider Implications of the Findings: The guideline provides clinicians with clear advice on best practice in RPL, based on the best and most recent evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. Still, the absence of a unified definition of RPL is one of the most critical consequences of the limited scientific evidence in the field.; Study Funding/competing Interests: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment.O.B.C. reports being a member of the executive board of the European Society for Reproductive Immunology and has received payment for honoraria for giving lectures about RPL in Australia in 2020. M.G. reports unconditional research and educational grant received by the Centre for Reproductive Medicine, Amsterdam UMC from Guerbet, Merck and Ferring, not related to the presented work. S.L. reports position funding from EXAMENLAB Ltd. and ownership interest by stock or partnership of EXAMENLAB Ltd (CEO). S.Q. reports being a deputy director of Tommy's National centre for miscarriage research, with payment received by the institution for research, staff time, and consumables for research. H.S.N. reports grants with payment to institution from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, the Danish ministry of Education, Novo Nordic Foundation, Aug stinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond, and Independent Research Fund Denmark and speakers' fees for lectures from Ferring Pharmaceuticals, Merck A/S, Astra Zeneca, IBSA Nordic and Cook Medical. She also reports to be an unpaid founder and chairman of a maternity foundation. M.-L.v.d.H. received small honoraria for lectures on RPL care. The other authors have no conflicts of interest to declare.; Disclaimer: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained.Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.). (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Bender, R. A. (2022). "Medroxyprogesterone Acetate for Abnormal Uterine Bleeding Due to Ovulatory Dysfunction: The Effect of 2 Different-Duration Regimens." Medical Science Monitor 28: e936727.
	Background: Abnormal uterine bleeding (AUB) lowers the quality of life of women. This study attempted to determine which treatment protocol of medroxyprogesterone acetate (MPA), 15 vs 10 day-administration in a luteal phase, provides better outcomes in women with ovulatory dysfunction-related AUB (AUB-O). Material/Methods: The study included a total of 52 patients with AUB-O: Women in Group A were given MPA between days 11 and 25 of the menstrual cycle (15-day protocol), whereas women in Group B were given MPA between days 16 and 25 (10-day protocol). Outcomes were compared between the 2 groups. Result(s): Women in group B, compared with those in group A, more often showed regular menstrual cycles and decrement of AUB. In group B, 3 cycles of treatment were sufficient to achieve AUB-stop (p<0.05). Post-treatment hemogram parameters and surgical treatment requirements were not different between the 2 groups. Conclusion(s): In the second half of the cycle/predicted luteal phase, 10-day cyclic use of MPA (the group B) better regulated the menstrual cycle and more frequently stopped AUB-O.Copyright © Med Sci Monit, 2022

Bendifallah, S., et al. (2021). "Surgical Outcomes after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(3): 453-466.
	Objective: To assess the impact of type of surgery for colorectal endometriosis-rectal shaving or discoid resection or segmental colorectal resection-on complications and surgical outcomes.; Data Sources: We performed a systematic review of all English- and French-language full-text articles addressing the surgical management of colorectal endometriosis, and compared the postoperative complications according to surgical technique by meta-analysis. The PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases were searched for relevant studies published before March 27, 2020. The search strategy used the following Medical Subject Headings terms: ("bowel endometriosis" or "colorectal endometriosis") AND ("surgery for endometriosis" or "conservative management" or "radical management" or "colorectal resection" or "shaving" or "full thickness resection" or "disc excision") AND ("treatment", "outcomes", "long term results" and "complications").; Methods of Study Selection: Two authors conducted the literature search and independently screened abstracts for inclusion, with resolution of any difference by 3 other authors. Studies were included if data on surgical management (shaving, disc excision, and/or segmental resection) were provided and if postoperative outcomes were detailed with at least the number of complications. The risk of bias was assessed according to the Cochrane recommendations.; Tabulation, Integration, and Results: Of the 168 full-text articles assessed for eligibility, 60 were included in the qualitative synthesis. Seventeen of these were included in the meta-analysis on rectovaginal fistula, 10 on anastomotic leakage, 5 on anastomotic stenosis, and 9 on voiding dysfunction <30 days. The mean complication rate according to shaving, disc excision, and segmental resection were 2.2%, 9.7%, and 9.9%, respectively. Rectal shaving was less associated with rectovaginal fistula than disc excision (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.10-0.36; p <.001; I 2 = 33%) and segmental colorectal resection (OR = 0.26; 95% CI, 0.15-0.44; p <.001; I 2 = 0%). No difference was found in the occurrence of rectovaginal fistula between disc excision and segmental colorectal resection (OR = 1.07; 95% CI, 0.70-1.63; p = .76; I 2 = 0%). Rectal shaving was less associated with leakage than disc excision (OR = 0.22; 95% CI, 0.06-0.73; p = .01; I 2 = 86%). No difference was found in the occurrence of leakage between rectal shaving and segmental colorectal resection (OR = 0.32; 95% CI, 0.10-1.01; p = .05; I 2 = 71%) or between disc excision and segmental colorectal resection (OR = 0.32; 95% CI, 0.30-1.58; p = .38; I 2 = 0%). Disc excision was less associated with anastomotic stenosis than segmental resection (OR = 0.15; 95% CI, 0.05-0.48; p = .001; I 2 = 59%). Disc excision was associated with more voiding dysfunction <30 days than rectal shaving (OR = 12.9; 95% CI, 1.40-119.34; p = .02; I 2 = 0%). No difference was found in the occurrence of voiding dysfunction <30 days between segmental resection and rectal shaving (OR = 3.05; 95% CI, 0.55-16.87; p = .20; I 2 = 0%) or between segmental colorectal and discoid resections (OR = 0.99; 95% CI, 0.54-1.85; p = .99; I 2 = 71%).; Conclusion: Colorectal surgery for endometriosis exposes patients to a risk of severe complications such as rectovaginal fistula, anastomotic leakage, anastomotic stenosis, and voiding dysfunction. Rectal shaving seems to be less associated with postoperative complications than disc excision and segmental colorectal resection. However, this technique is not suitable for all patients with large bowel infiltration. Compared with segmental colorectal resection, disc excision has several advantages, including shorter operating time, shorter hospital stay, and lower risk of postoperative bowel stenosis. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Bendifallah, S., et al. (2020). "Recurrence after Surgery for Colorectal Endometriosis: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 27(2): 441.
	Objective: The recurrence rate after colorectal surgery for endometriosis is up to 50% at 5 years. The aim of the current review and meta-analysis was to assess recurrence associated with shaving, disc excision, and segmental resection for endometriosis with colorectal involvement.; Data Sources: A systematic review was performed by searching the PubMed, ClinicalTrials.gov, EMBASE, Cochrane Library, and Web of Science databases for publications before February 28, 2019, using the terms "colorectal endometriosis" and "recurrence" in English. The outcome measure was histologically proven recurrence 1 year after the index surgery.; Methods of Study Selection: Studies rated as good or fair by a study quality assessment tool were included. Two reviewers independently assessed the quality of the studies; discrepancies were discussed, and if a consensus was not reached, a third reviewer was consulted.; Tabulation, Integration, and Results: Of 156 relevant published trials, 41 were systematically reviewed and 4 were included in the meta-analysis. The risk of recurrence was higher after rectal shaving than after both segmental resection (odds ratio [OR], 5.53; 95% confidence interval [CI], 2.33-13.12; I 2 = 0%; p = .001) and disc excision for histologically proven recurrence (OR, 3.83; 95% CI, 1.33-11.05; I 2 = 0%; p = .01). This difference was not significant when comparing disc excision with segmental resection (OR, 2.63; 95% CI, 0.8-8.65; I 2 = 0%; p = .11).; Conclusion: The current analysis shows that the risk of recurrence is lower when segmental resection or disc excision is performed than when rectal shaving is performed. This finding is important when deciding the most appropriate surgical management. (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Benna-Doyle, S., et al. (2024). "Nutritional interventions during treatment for ovarian cancer: A narrative review and recommendations for future research." Maturitas 183: 107938.
	Most women with ovarian cancer are diagnosed at an advanced stage (stage III or IV), when the intraabdominal spread of the tumour impacts nutrient intake and absorption. Up to 70 % of women with ovarian cancer are malnourished and approximately 40 % are affected by muscle loss at the time of diagnosis. Women with ovarian cancer are at high risk of nutritional decline due to invasive treatment and the severity of side-effects. This review explores the evidence evaluating nutritional interventions during treatment for ovarian cancer and their effect on nutritional status, muscle mass, and clinical outcomes. Perioperative immunonutrition has been investigated with mixed results for immediate postoperative outcomes. Individualised nutrition counselling as part of a multimodal prehabilitation programme prior to surgery shows promising results; however, the effects are limited by sample size. Nutrition counselling as part of a mixed intervention with exercise shows high acceptability and suggests improvements in dietary intake and quality of life during chemotherapy treatment, while oral nutritional supplements and nutrition education appear to reduce symptom burden. Individualised nutrition counselling during treatment also appears to be associated with improved overall survival; however, the evidence is limited to a single retrospective study. A key finding from this review is that, despite the high prevalence of malnutrition and muscle loss in women with ovarian cancer and the critical importance of addressing these modifiable prognostic factors, nutrition intervention studies are limited. Prospective studies with samples large enough to provide adequate power to evaluate intervention effectiveness are urgently required to inform optimal management.Copyright © 2024 The Authors

Bennett, A., et al. (2019). "Effectiveness of Outpatient Versus Operating Room Hysteroscopy for the Diagnosis and Treatment of Uterine Conditions: A Systematic Review and Meta-Analysis." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 41(7): 930-941.
	Traditionally, hysteroscopy has been performed in the main operating room with the patient under general anaesthesia. Hysteroscopy performed in an office setting avoids the risks of general anaesthesia. The aim of this review was to evaluate the effectiveness of outpatient hysteroscopy compared with hysteroscopy performed in the operating room to diagnose and/or treat intrauterine pathology. Relevant electronic databases were searched, including Medline, EMBASE, and the Cochrane Library. RCTs and nonrandomized studies that compared the efficacy of outpatient hysteroscopy and traditional hysteroscopy performed in the operating room were included. The primary outcome of interest was diagnostic accuracy, and secondary outcomes included treatment success, adverse events, pain, patient satisfaction, and cost. The Cochrane risk of bias tool was used to assess RCTs, and the Downs and Black tool was used for nonrandomized studies. A total of 12 658 abstracts and 347 full-text articles were assessed, from which a total of 20 full-text studies met our eligibility criteria. No study compared the diagnostic accuracy of outpatient hysteroscopy with hysteroscopy performed in the operating room. There was no significant difference between hysteroscopy performed in the outpatient and operating room setting for treatment success, adverse events, and patient satisfaction. In the included RCTs, there was greater reported postoperative pain in the outpatient setting (standard mean difference 0.19, 95% CI 0.01-0.37). All seven economic studies concluded that outpatient hysteroscopy (range US$97-1258) is substantially less expensive than hysteroscopy performed in the operating room (range US$258-3144). Included RCTs had serious risks of selection, performance, and detection bias. The results of this review demonstrate that implementing hysteroscopy in an outpatient setting without general anaesthesia should be thoughtfully considered. The current available evidence demonstrates greater reported postoperative pain in the outpatient setting and no statistically significant differences in all other studied outcome measures between outpatient and intraoperative hysteroscopy procedures. (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Berahman, H., et al. (2021). "The effect of water-based rhythmic exercise training on glucose homeostasis and thyroid hormones in postmenopausal women with metabolic syndrome." Hormone molecular biology and clinical investigation 42(2): 189‐193.
	OBJECTIVES: The present study aimed to explore the effect of water‐based rhythmic exercise training on fasting blood sugar (FBS), homeostatic model assessment (HOMA), insulin, thyroid stimulating hormone (TSH), and T4 in postmenopausal women with metabolic syndrome. METHODS: In this clinical trial, 31 postmenopausal woman with metabolic syndrome aged 69.16 ± 2.02 years were randomly assigned to an experimental (n=16) and a control group (n=15). The training program was composed of 12 weeks of water‐based rhythmic exercise training performed intermittently for 60 min three times a week. Before and after training, blood was analyzed for glucose homeostasis, T4, and TSH. Data were subjected to analysis by paired t‐test and covariance analysis at the p<0.05 level. RESULTS: The exercise training intervention reduced the FBS and insulin significantly (p=0.000). The growth hormone (GH) index was increased significantly only in the experimental group (p=0.037) whereas no significant variations occurred in the insulin‐like growth factor‐1 (p=0.712). It was also found that TSH and T4 change in the experimental group as compared to the pre‐test. CONCLUSIONS: Water‐based rhythmic exercise training may improve blood glucose homeostasis, TSH, and T4.

Bercow, A., et al. (2021). "Outcomes after Fertility-sparing Surgery for Women with Ovarian Cancer: A Systematic Review of the Literature." Journal of Minimally Invasive Gynecology 28(3): 527.
	Objective: To compare reproductive and oncologic outcomes of patients diagnosed with early-stage epithelial ovarian carcinoma, borderline ovarian tumors, or nonepithelial ovarian carcinoma according to receipt of fertility-sparing surgery or conventional surgery.; Data Sources: PubMed was searched from January 1, 1995, to May 29, 2020.; Methods of Study Selection: Studies were included if they (1) enrolled women of childbearing age diagnosed with ovarian cancer between the ages of 18 years and 50 years, (2) reported on oncologic and/or reproductive outcomes after fertility-sparing surgery for ovarian cancer, and (3) included at least 20 patients.; Tabulation, Integration, and Results: The initial search identified 995 studies. After duplicates were removed, we abstracted 980 unique citations. Of those screened, 167 publications were identified as potentially relevant, and evaluated for inclusion and exclusion criteria. The final review included 44 studies in epithelial ovarian cancer, 42 in borderline ovarian tumors, and 31 in nonepithelial ovarian carcinoma. The narrative synthesis demonstrated that overall survival does not seem to be compromised in patients undergoing fertility-sparing surgery compared with those undergoing conventional surgery, although long-term data are limited. Areas of controversy include safety of fertility-sparing surgery in the setting of high-risk factors (stage IC, grade 3, and clear cell histology), as well as type of surgery (salpingo-oophorectomy vs cystectomy). It seems that although there may be some fertility compromise after surgery, pregnancy and live-birth rates are encouraging.; Conclusion: Fertility-sparing surgery is safe and feasible in women with early-stage low-risk ovarian cancer. Pregnancy outcomes for these patients also seem to be similar to those of the general population. (Copyright © 2020. Published by Elsevier Inc.)

Bercow, A. S., et al. (2023). "Association of hospital-level factors with utilization of sentinel lymph node biopsy in patients with early-stage vulvar cancer." Gynecologic Oncology 169: 47-54.
	Objective: To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities. Method(s): Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. Result(s): Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19-0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28-0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63-1.66) or negative (HR 0.92, 95% CI 0.70-1.21) nodal pathology. Conclusion(s): For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care.Copyright © 2022 Elsevier Inc.

Berd, D. (2023). "Portrait of an autologous cancer vaccine: Then and now." Human vaccines & immunotherapeutics 19(1): 2172925.
	Active immunotherapy of cancer with therapeutic vaccines has been the subject of experimental and clinical studies for at least 50 years. Our approach has employed 1) autologous, human cancer cells because of extensive evidence that tumor rejection antigens may differ between multiple tumors of the same histology; 2) the immunopotentiating drug, cyclophosphamide; and 3) haptens, particularly dinitrophenyl. Multiple clinical trials in 455 patients with melanoma and ovarian cancer have shown that administration of haptenized vaccines at the proper dosage-schedule regularly induces T cell-mediated immunity to autologous tumor cells as measured by delayed-type hypersensitivity. Moreover, the vaccine causes changes in the tumor site suggestive of an immune reaction, including inflammation and infiltration with CD8+ T lymphocytes that are activated and produce cytokines. The T cell response is oligoclonal, and dominant Vβ families differ between patients. Studies of measurable metastases show clinically important tumor regression. Commercial development of this technology is clearly feasible.

Berestoviy, V. O., et al. (2021). "AN OVERVIEW OF AUTOIMMUNITY IN IMPLANTATION FAILURE: A LITERATURE REVIEW." Wiadomosci lekarskie (Warsaw, Poland : 1960) 74(3 cz 2): 777-783.
	OBJECTIVE: The aim: This review was aimed to understand the role of different types of autoantibodies like antiphospholipid, antithyroid, antisperm, antinuclear, anti-ovarian autoantibodiesand heat shock protein HSP 60 in the process of implantation in the normal way of conceiving and IVF and also to estimate that how the presence of these autoantibodies affect the normal pregnancy outcome. PATIENTS AND METHODS: Material(s) and Method(s): This review process performed in the obstetrics and gynaecology postgraduate department, Bogomolets national medical university, Kyiv, Ukraine. It was a review of already published papers not to need the ethical board committee's approval. By following the literature review guidelines, this paper was written and searched for relevant studies regarding autoantibodies and implantation, published in medical literature till 2020 were included in this review process. The search is done for studies published till 2020 in the English language from the Medline database, including Google Scholar, PubMed, Web of Science and Cochrane library database. CONCLUSION(S): Conclusion(s): Our recent work found that the involvement of APA, ANA and/or ATA in recipients of oocyte donations did not affect their pregnancy outcomes. Some researchers did not give any clear conclusion about these risks, and some stated that the use of some immunodepressant agents could be useful to reduce the harmful effects of these autoantibodies associated with implantation failure. Each autoantibody has a different mechanism of action to create the pathological state, some have direct effect, and some indirectly impact implantation. In future, further high-quality studies need to be performed for better understanding.

Berezowska, A., et al. (2021). "Professional patient navigation in a hospital setting: a randomized controlled trial." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 29(4): 2111-2123.
	PURPOSE: This study aimed to determine the effect of patient navigation on health-related quality of life, distress, self-care knowledge, self-efficacy, satisfaction, and healthcare usage. METHODS: Patients newly diagnosed with ovarian, vulvar, endometrial, melanoma stage III/IV, lung, or renal cancer were randomly assigned to either care as usual or care as usual plus consultations with a patient navigator (i.e., specially trained oncology nurse who monitors, advises, and refers patients to supportive cancer care). Measures included the EORTC-QLQ-C30, distress thermometer, and study-specific questions inspired by the Symptom-Management Self-Efficacy Scale Breast Cancer, Patient Satisfaction with Cancer Care Scale, and the Medical Consumption Questionnaire. Measures were completed before randomization (baseline) and at 1 month, 3 months, and 5 months after baseline. RESULTS: In the case of health-related quality of life, no significant difference was observed between the intervention (n = 42) and the control group (n = 47). Consumption of supportive cancer care was low for both the intervention and the control group but relatively lower for the intervention group. Also, participants who consulted the patient navigator seemed to have higher levels of self-efficacy and satisfaction. CONCLUSION: Although the intervention sorted no relevant effects on health-related quality of life, it did affect patients' experience of cancer care and self-efficacy. We recommend that patient navigators monitor and advise on unmet supportive care needs, but only in the case of high-risk patients. Furthermore, considering current and prior research, it is wise to study patient navigation using more sensitive outcome measures than health-related quality of life.

Bergamini, A., et al. (2022). "Fertility sparing surgery in sex-cord stromal tumors: oncological and reproductive outcomes." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(8): 1063-1070.
	Sex cord stromal tumors are rare neoplasms, frequently diagnosed in young women often as early-stage disease. In patients who desire to preserve fertility, when possible, unilateral salpingo-oophorectomy with peritoneal surgical staging is a safe alternative to radical treatment. In this review, we analyze the available literature on the obstetrical outcomes after fertility-sparing surgery in a total of 255 patients with sex cord stromal tumors. We found that the spontaneous conception rate in granulosa cells tumor is encouraging (88.5%). In particular, juvenile granulosa cell tumors are associated with a more successful pregnancy rate than adult granulosa cells tumors (11/26 (42.3%) in juvenile granulosa cells tumors compared with 28.5% in adult granulosa cell tumors, respectively.) On the other hand, the results of obstetrical outcomes in Sertoli-Leydig cells tumors are less promising (7/36 (19.4%)). Unfortunately, no evidence on this topic is available for sex cord tumor with annular tubules due to the low incidence. Regarding the oncological outcomes of 900 cases of sex cord stromal tumors treated conservatively, data are reassuring with comparable outcomes between patients treated with conservative and radical surgery. Given the limited available data on this rare tumor, further studies are needed to evaluate the safety of conservative approaches and to define the obstetrical outcomes in this patient population.

Bergenheim Sara, J., et al. (2021). "Immediate versus postponed single blastocyst transfer in modified natural cycle frozen embryo transfer (mNC-FET): a study protocol for a multicentre randomised controlled trial." BMJ Open 11(10): e053234.
	Introduction: Today, it is widespread practice to postpone frozen embryo transfer (FET) in a modified natural cycle (mNC) for at least one menstrual cycle after oocyte retrieval and failed fresh embryo transfer or freeze-all. The rationale behind this practice is the concern that suboptimal ovarian, endometrial or endocrinological conditions following ovarian stimulation may have a negative impact on endometrial receptivity and implantation. However, two recent systematic reviews and meta-analyses based on retrospective data did not support this practice. As unnecessary delay in time to transfer and pregnancy should be avoided, the aim of this study is to investigate if immediate single blastocyst transfer in mNC-FET is non-inferior to standard postponed single blastocyst transfer in mNC-FET in terms of live birth rate.; Methods and Analysis: Multicentre randomised controlled non-blinded trial including 464 normo-ovulatory women aged 18-40 years undergoing single blastocyst mNC-FET after a failed fresh or freeze-all cycle. Participants are randomised 1:1 to either FET in the first menstrual cycle following the stimulated cycle (immediate FET) or FET in the second or subsequent cycle following the stimulated cycle (postponed FET). The study is designed as a non-inferiority trial and primary analyses will be performed as intention to treat and per protocol.; Ethics and Dissemination: Ethical approval has been granted by the Scientific Ethical Committee of the Capital Region of Denmark (J-nr.: H-19086300). Data will be handled according to Danish law on personal data protection in accordance with the general data protection regulation. Participants will complete written consent forms regarding participation in the study and storage of blood samples in a biobank for future research. The study will be monitored by a Good Clinical Practice (GCP)-trained study nurse not otherwise involved in the study. The results of this study will be disseminated by publication in international peer-reviewed scientific journals.; Trial Registration Number: NCT04748874; Pre-results.; Competing Interests: Competing interests: ABP and KL has received a research grant from Merck supporting the present study. SJB has received a research grant from Rigshospitalet’s research fund supporting the present study. As a partner of Reprounion, ABP has received a grant from Ferring as well as a research grant from Gedeon Richter. ABP has received consulting fees from Novo Nordisk, honoraria from Merck and Ferring, honoraria as well as support for attending meetings from Gedeon Richter. KL has received honoraria from pharmakon and support for attending meetings from Gedeon Richter. PH has received unrestricted grants from Merck, Gedeon Richter, IBSA, Ferring and MSD as well as honoraria for lectures from Merck and Gedeon Richter. MF has received a research grant from Gedeon Richter. NLCF has received an unrestricted grant from Gedeon Richter, honoraria for lectures from Merck and support for attending meetings by Ferring, Merck and Gedeon Richter. Since 2018, NLCF is head of the steering committee for Danish fertility guidelines. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Berger, T., et al. (2019). "Importance of Technique, Target Selection, Contouring, Dose Prescription, and Dose-Planning in External Beam Radiation Therapy for Cervical Cancer: Evolution of Practice From EMBRACE-I to II." International Journal of Radiation Oncology, Biology, Physics 104(4): 885-894.
	Purpose: To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT).; Methods and Materials: EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43 Gy), and conformity index (CI; V43 Gy/PTV) were evaluated in both studies and compared.; Results: For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50 Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390 mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43 Gy volumes were 1921 and 2895 mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46 Gy, the use of conformal radiation therapy was associated with a median V43 Gy volume that was 546 mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription ≥48 Gy was associated with a median V43 Gy volumes that was 428 mL larger than with a dose prescription of 45 to 46 Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45 Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43 Gy volumes were 1388 and 1418 mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43 Gy volumes were 1720 and 1765 mL, and CI was 1.03. From EMBRACE-I to initial II, median V43 Gy was decreased by 972 mL (41%) and 1130 mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively.; Conclusions: Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43 Gy and V50 Gy and improves conformality and interinstitutional consistency. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bergeron, C., et al. (2020). "Endometrial ablation or resection versus levonorgestrel intra-uterine system for the treatment of women with heavy menstrual bleeding and a normal uterine cavity: a systematic review with meta-analysis." Human Reproduction Update 26(2): 302-311.
	Background: Endometrial ablation/resection and the levonorgestrel intra-uterine system (LNG-IUS) are well-established treatment options for heavy menstrual bleeding to avoid more invasive alternatives, such as hysterectomy.; Objective: The aim was to compare the efficacy and safety of endometrial ablation or resection with the LNG-IUS in the treatment of premenopausal women with heavy menstrual bleeding and to investigate sources of heterogeneity between studies.; Search Methods: We searched the databases MEDLINE, EMBASE, CENTRAL, Web of Science, Biosis and Google Scholar as well as citations and reference lists published up to August 2019. Two authors independently screened 3701 citations for eligibility. We included randomized controlled trials published in any language, comparing endometrial ablation or resection to the LNG-IUS in the treatment of premenopausal women with heavy menstrual bleeding and a normal uterine cavity.; Outcomes: Thirteen studies (N = 884) were eligible. Two independent authors extracted data and assessed the quality of included studies. Random effect models were used to compare the modalities and evaluate sources of heterogeneity. No significant differences were observed between endometrial ablation/resection and the LNG-IUS in terms of subsequent hysterectomy (primary outcome, risk ratio (RR) = 1.13, 95% CI 0.60 to 2.11, P = 0.71, I2 = 14%, 12 studies, 726 women), satisfaction, quality of life, amenorrhea and treatment failure. However, side effects were less common in women treated with endometrial ablation/resection compared to the LNG-IUS (RR = 0.52, 95% CI 0.37 to 0.71, P < 0.001, I2 = 0%, 10 studies, 580 women). Three complications were reported in the endometrial ablation/resection group and none in the LNG-IUS group (P = 0.25). Mean age of the studied populations was identified as a significant source of heterogeneity between studies in subgroup analysis (P = 0.01). In fact, endometrial ablation/resection was associated with a higher risk of subsequent hysterectomy compared to the LNG-IUS in younger populations (mean age ≤ 42 years old, RR = 5.26, 95% CI 1.21 to 22.91, P = 0.03, I2 = 0%, 3 studies, 189 women). On the contrary, subsequent hysterectomy seemed to be less likely with endometrial ablation/resection compared to the LNG-IUS in older populations (mean age > 42 years old), although the reduction did not reach statistical significance (RR = 0.51, 95% CI 0.21 to 1.24, P = 0.14, I2 = 0%, 5 studies, 297 women). Finally, sensitivity analysis taking into account the risk of bias of included studies and type of surgical devices (first and second generation) did not modify the results. Most of the included studies reported outcomes at up to 3 years, and the relative performance of endometrial ablation/resection and LNG-IUS remains unknown in the longer term.; Wider Implications: Endometrial ablation/resection and the LNG-IUS are two excellent treatment options for heavy menstrual bleeding, although women treated with the LNG-IUS are at higher risk of experiencing side effects compared to endometrial ablation/resection. Otherwise, younger women seem to present a lower risk of eventually requiring hysterectomy when treated with the LNG-IUS compared to endometrial ablation/resection. (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bergeron, S., et al. (2021). "Cognitive-behavioral couple therapy versus lidocaine for provoked vestibulodynia: A randomized clinical trial." Journal of Consulting and Clinical Psychology 89(4): 316-326.
	Public Health Significance-This study shows that CBCT is an efficacious treatment for women with a subset of genito-pelvic pain and that involving partners may be beneficial. (PsycInfo Database Record (c) 2021 APA, all rights reserved), Objective: This randomized clinical trial compared a novel cognitive-behavioral couple therapy (CBCT) and topical lidocaine for provoked vestibulodynia. Method(s): Participants were 108 women (M age = 27.06) and their partners randomized to one of two treatments and assessed at pre- and post-treatment and 6-month follow-up via questionnaires pertaining to the primary outcomes of women's pain (numerical rating scales of pain intensity and unpleasantness), and secondary outcomes of pain anxiety (Pain Anxiety Symptoms Scale), both partners' sexual function (Female Sexual Function Index; International Index of Erectile Function), sexual distress (Female Sexual Distress Scale Revised), pain-related psychological distress (Pain Catastrophizing Scale), treatment satisfaction, and global ratings of improvements in pain and sexuality. Result(s): Intent-to-treat multilevel analyses showed that for women, CBCT yielded significantly more improvements than lidocaine in pain unpleasantness at 6-month follow-up, pain anxiety and pain catastrophizing at post-treatment and 6-month follow-up, and sexual distress at post-treatment, and resulted in better treatment satisfaction and global sexuality improvements at both time points. Partners significantly improved in their sexual function, sexual distress, and pain catastrophizing from pre- to post-treatment and pre-treatment to 6-month follow-up, with no significant group differences. Partners in the CBCT condition reported significantly greater treatment satisfaction at both time points, and greater sexuality improvements at post-treatment. Conclusion(s): CBCT yielded better outcomes on more dimensions of provoked vestibulodynia than lidocaine. (PsycInfo Database Record (c) 2021 APA, all rights reserved)Copyright © 2021 American Psychological Association

Bergersen, A., et al. (2019). "Management of vaginal mesh exposure: A systematic review." Arab Journal of Urology 17(1): 40-48.
	Objectives: To identify various predisposing factors, the clinical presentation, and the management of vaginal mesh-related complications, with special emphasis on mesh exposure and the indications for and results of vaginal mesh removal. Method(s): A systematic literature review was performed using a search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. PubMed was queried for studies regarding aetiology, risk factors, and management of vaginal mesh exposure from 1 January 2008 to June 2018. Full-text articles were obtained for eligible abstracts. Relevant articles were included, and the cited references were used to identify relevant articles not previously included. Result(s): A total of 102 abstracts were identified from the PubMed search criteria. An additional 45 studies were identified based on review of the cited references. After applying eligibility criteria and excluding impertinent articles, 58 studies were included in the final analysis. Conclusion(s): Numerous studies have found at least some degree of symptomatic improvement regardless of the amount of mesh removed. Focal areas of exposure or pain can be successfully managed with partial mesh removal with low rates of complications. With partial mesh removal, many patients will ultimately require subsequent mesh removal procedures. For this reason, complete mesh excision is an alternative for patients with diffuse vaginal pain, large mesh exposure, and extrusion of mesh into adjacent viscera. However, when considering complete mesh removal, it is important to counsel patients regarding possible complications of removal and the increased risk of recurrent stress urinary incontinence and pelvic organ prolapse postoperatively. Abbreviations: MUS: midurethral sling; OR: odds ratio; POP: pelvic organ prolapse; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; SUI: stress urinary incontinence; TOT: transobturator; TVT: tension-free vaginal tape.Copyright © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Bergonié, I. (2021). Impact of Specific Monitoring of Intraoperative Analgesia Under General Anesthesia on Chronic Pain After Ovarian Cancer Surgery.
	No Results Available Other: Arm A : intraoperative ANI monitoring of nociception|Other: Arm B : no specific monitoring of nociception Proportion of patients with a pain score on the self-assessment VAS > 4, three months after the surgery.|Arm A : total dose of opioids received intraoperatively|Arm B : total dose of opioids received intraoperatively|Arm A : Patients' pain score on the VAS immediately postoperatively|Arm B : Patients' pain score on the VAS immediately postoperatively|Arm A : proportion of patients with a DN4 questionnaire score> 4, three months after surgery|Arm B : Arm A : proportion of patients with a DN4 questionnaire score> 4, three months after surgery Female Not Applicable 126 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Other IB 2020-04|2020-A02767-32 August 25, 2024

Berlin, J., et al. (2022). "First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies." Investigational New Drugs 40(3): 586-595.
	Purpose. Sym013 contains six humanized monoclonal antibodies that bind to non-overlapping epitopes on three human epidermal growth factor receptors (HER1-3). Preclinical studies suggested Sym013 strongly suppresses growth of multiple epithelial tumors. This is a first-in-human study exploring safety and efficacy of Sym013 in patients with advanced epithelial malignancies. Methods. Dose escalation used single-patient cohorts until the stopping rule was met, followed by 3 + 3 design. Dose levels planned were: 1, 2, 4, 6, 9, 12, 15, and 18 mg/kg. Treatment cycles were 28 days with imaging every eight weeks. Serum samples were collected at multiple time points for assessment of pharmacokinetics and development of anti-drug antibodies. Results. Thirty-two patients were enrolled with multiple solid tumors, most common being colorectal cancer (CRC; 10/32, 31%). Due to mucositis, rash, and diarrhea at 4 mg/kg once-weekly, dosing was changed to biweekly (Q2W). Mandatory prophylaxis was added due to Grade 3 infusion-related reaction and oral mucositis at 9 mg/kg Q2W. The 15 mg/kg Q2W cohort was enrolling when the study was terminated for business reasons. Most common adverse events were skin (81%) and gastrointestinal (75%) disorders, including dermatitis/rash, stomatitis, and diarrhea. One patient with CRC achieved a partial response; 12 patients with varied malignancies had stable disease. Conclusion. During the conduct of the study, management of frequent infusion-related reactions, skin toxicities, and mucosal disorders, which are indicative of HER inhibition, necessitated multiple protocol amendments. The investigators, in concert with the Sponsor, agreed that achieving a tolerated regimen with acceptable target saturation was unlikely. Trial registry: www.clinicaltrials.gov; NCT02906670 (September 20, 2016).Copyright © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Bernabeu, I. (2022). Continuous Double Ovarian Stimulation.
	No Results Available Drug: Corifollitropin Alfa|Drug: Follitropin Alfa|Drug: Follitropin Alfa Biosimilar|Drug: Urinary Human follicle stimulating hormone number of retrieved oocytes - study group|number of retrieved oocytes - comparison|number of MII oocytes - comparison|duration of DUOSTIM cycle - comparison|fertilization rate - comparison Female Phase 4 30 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment IBMR31|2022-003177-32 May 30, 2023

Bernard, L., et al. (2021). "The levonorgestrel intrauterine system (LNG-IUS) for prevention of endometrial cancer in women with obesity is cost effective." Gynecologic Oncology 162(Supplement 1): S300-S301.
	Objectives: To estimate the cost-effectiveness of the levonorgestrel intrauterine system (LNG-IUS) as an endometrial cancer prevention strategy in women with obesity. Method(s): A Markov decision-analytic model was used to compare 5 strategies in women with a body mass index of 30 or greater: 1) Usual care 2) LNG-IUS for 5 years 3) LNG-IUS for 7 years 4) LNG-IUS for 5 years, replaced once for a total of 10 years 5) LNG-IUS for 7 years, replaced once for a total of 14 years. Obesity was presumed to be associated with a 3-fold relative risk of endometrial cancer incidence and a 2.65-fold disease-specific mortality. The LNG-IUS was assumed to confer a 50% reduction in cancer incidence over the period of the LNG-IUS insertion. Costs of LNG-IUS and cancer care were included. Outcomes were incremental cost-effectiveness ratios, calculated in 2019 Canadian dollars per year of life saved. One-way and two-way sensitivity analyses were performed. Result(s): The LNG-IUS strategy was considered cost-effective if the cost of the intervention is less than 66 400 CAD (50 000 USD) per year of life saved. The strategy becomes cost-effective if 1 LNG-IUS is inserted in 57-year-old women for 5 years, 1 LNG-IUS is inserted in 52-year-old women for 7 years, 2 subsequent LNG-IUS for a total of 10 years are inserted in 51-year-old women or 2 subsequent LNG-IUS for a total of 14 years are inserted in 45-year-old women, when compared to usual care. The results are stable to variations in cost but sensitive to the estimated risk reduction of the LNG-IUS and the impact of obesity on endometrial cancer incidence and disease-specific mortality. Conclusion(s): The LNG-IUS is a cost-effective method of endometrial cancer prevention in women with obesity. This intervention warrants investigation in a prospective study in this high-risk population.Copyright © 2021 Elsevier Inc.

Bernard, L., et al. (2021). "The levonorgestrel intrauterine system for prevention of endometrial cancer in women with obesity: A cost-effectiveness study." Gynecologic Oncology 161(2): 367-373.
	Objective: To estimate the cost-effectiveness of the levonorgestrel intrauterine system (LNG-IUS) as an endometrial cancer prevention strategy in women with obesity. Method(s): A Markov decision-analytic model was used to compare 5 strategies in women with a body mass index of 30 or greater: 1) Usual care 2) LNG-IUS for 5 years 3) LNG-IUS for 7 years 4) LNG-IUS for 5 years, replaced once for a total of 10 years 5) LNG-IUS for 7 years, replaced once for a total of 14 years. Obesity was presumed to be associated with a 3-fold relative risk of endometrial cancer incidence and a 2.65-fold disease-specific mortality. The LNG-IUS was assumed to confer a 50% reduction in cancer incidence over the period of the LNG-IUS insertion. Outcomes were incremental cost-effectiveness ratios, calculated in 2019 Canadian dollars (CAD) per year of life saved. One-way and two-way sensitivity analyses were performed. Result(s): The LNG-IUS strategy was considered cost-effective if the cost of the intervention is less than $66,400 CAD ($50,000 US dollars) per year of life saved. The strategy becomes cost-effective if the LNG-IUS is inserted at age 57 (strategy #2), at age 52 for strategy #3, at age 51 for strategy #4 and at age 45 for strategy #5, when compared to usual care. The results are stable to variations in cost but sensitive to the estimated risk reduction of the LNG-IUS and the impact of obesity on endometrial cancer incidence and disease-specific mortality. Conclusion(s): The LNG-IUS is a cost-effective method of endometrial cancer prevention in women with obesity.Copyright © 2021 Elsevier Inc.

Bernard, L., et al. (2023). "A Double-blinded, Randomized Trial Comparing Surgeon-Administered Transversus Abdominis Plane Block With Placebo After Midline Laparotomy in Gynecologic Oncology Surgery." Obstetrical and Gynecological Survey 78(7): 404-405.
	Background: Surgeon-administered transversus abdominis plane block is a contemporary approach to providing postoperative analgesia, and this approach is performed by transperitoneally administering local anesthetic in the plane between the internal oblique and transversus abdominis muscles to target the sensory nerves of the anterolateral abdominal wall. Although this technique is used in many centers, it has not been studied prospectively in patients undergoing a midline laparotomy. Objective: This study aimed to evaluate whether surgeon-administered transversus abdominis plane block reduces postoperative opioid requirements and improves clinical outcomes. Study design: In this double-blind, randomized, placebo-controlled trial, patients with a suspected or proven gynecologic malignancy undergoing surgery through a midline laparotomy at 1 Canadian tertiary academic center were randomized to either the bupivacaine group (surgeon-administered transversus abdominis plane blocks with 40 mL of 0.25% bupivacaine) or the placebo group (surgeon-administered transversus abdominis plane blocks with 40 mL of normal saline solution) before fascial closure. The primary outcome was the total dose of opioids (in morphine milligram equivalents) received in the first 24 hours after surgery. The secondary outcomes included opioid doses between 24 and 48 hours, pain scores, postoperative nausea and vomiting, incidence of clinical ileus, time to flatus, and hospital length of stay. The exclusion criteria included contraindications to study medication, history of chronic opioid use, significant adhesions on the anterior abdominal wall preventing access to the injection site, concurrent nonabdominal surgical procedure, and the planned use of neuraxial anesthesia or analgesia. To detect a 20% decrease in opioid requirements with a 2-sided type 1 error of 5% and power of 80%, a sample size of 36 patients per group was calculated. Results: From October 2020 to November 2021, 38 patients were randomized to the bupivacaine arm, and 41 patients were randomized to the placebo arm. The mean age was 60 years, and the mean body mass index was 29.3. A supraumbilical incision was used in 30 of 79 cases (38.0%), and bowel resection was performed in 10 of 79 cases (12.7%). Patient and surgical characteristics were evenly distributed. The patients in the bupivacaine group required 98.0±59.2 morphine milligram equivalents in the first 24 hours after surgery, whereas the patients in the placebo group required 100.8±44.0 morphine milligram equivalents (P=.85). The mean pain score at 4 hours after surgery was 3.1±2.4 (0-10 scale) in the intervention group vs 3.1±2.0 in the placebo group (P=.93). Clinically significant nausea or vomiting was reported in 1 of 38 patients (2.6%) in the intervention group vs 1 of 41 patients (2.4%) in the placebo group (P=.95). Time to first flatus, rates of clinical ileus, and length of stay were similar between groups. Subgroup analysis of patients with a body mass index of <25 and patients who received an infraumbilical incision showed similarly comparable outcomes. Conclusion: Surgeon-administered transversus abdominis plane block with bupivacaine was not found to be superior to the placebo intervention in reducing postoperative opioid requirements or improving other postoperative outcomes for patients undergoing a midline laparotomy. These results differed from previous reports evaluating the ultrasound-guided transversus abdominis plane block approach. Surgeon-administered transversus abdominis plane block should not be considered standard of care in postoperative multimodal analgesia.

Bernard, L., et al. (2023). "A double-blinded, randomized trial comparing surgeon-administered transversus abdominis plane block with placebo after midline laparotomy in gynecologic oncology surgery." American Journal of Obstetrics and Gynecology 228(5): 553.e551-553.e558.
	Background: Surgeon-administered transversus abdominis plane block is a contemporary approach to providing postoperative analgesia, and this approach is performed by transperitoneally administering local anesthetic in the plane between the internal oblique and transversus abdominis muscles to target the sensory nerves of the anterolateral abdominal wall. Although this technique is used in many centers, it has not been studied prospectively in patients undergoing a midline laparotomy.; Objective: This study aimed to evaluate whether surgeon-administered transversus abdominis plane block reduces postoperative opioid requirements and improves clinical outcomes.; Study Design: In this double-blind, randomized, placebo-controlled trial, patients with a suspected or proven gynecologic malignancy undergoing surgery through a midline laparotomy at 1 Canadian tertiary academic center were randomized to either the bupivacaine group (surgeon-administered transversus abdominis plane blocks with 40 mL of 0.25% bupivacaine) or the placebo group (surgeon-administered transversus abdominis plane blocks with 40 mL of normal saline solution) before fascial closure. The primary outcome was the total dose of opioids (in morphine milligram equivalents) received in the first 24 hours after surgery. The secondary outcomes included opioid doses between 24 and 48 hours, pain scores, postoperative nausea and vomiting, incidence of clinical ileus, time to flatus, and hospital length of stay. The exclusion criteria included contraindications to study medication, history of chronic opioid use, significant adhesions on the anterior abdominal wall preventing access to the injection site, concurrent nonabdominal surgical procedure, and the planned use of neuraxial anesthesia or analgesia. To detect a 20% decrease in opioid requirements with a 2-sided type 1 error of 5% and power of 80%, a sample size of 36 patients per group was calculated.; Results: From October 2020 to November 2021, 38 patients were randomized to the bupivacaine arm, and 41 patients were randomized to the placebo arm. The mean age was 60 years, and the mean body mass index was 29.3. A supraumbilical incision was used in 30 of 79 cases (38.0%), and bowel resection was performed in 10 of 79 cases (12.7%). Patient and surgical characteristics were evenly distributed. The patients in the bupivacaine group required 98.0±59.2 morphine milligram equivalents in the first 24 hours after surgery, whereas the patients in the placebo group required 100.8±44.0 morphine milligram equivalents (P=.85). The mean pain score at 4 hours after surgery was 3.1±2.4 (0-10 scale) in the intervention group vs 3.1±2.0 in the placebo group (P=.93). Clinically significant nausea or vomiting was reported in 1 of 38 patients (2.6%) in the intervention group vs 1 of 41 patients (2.4%) in the placebo group (P=.95). Time to first flatus, rates of clinical ileus, and length of stay were similar between groups. Subgroup analysis of patients with a body mass index of <25 and patients who received an infraumbilical incision showed similarly comparable outcomes.; Conclusion: Surgeon-administered transversus abdominis plane block with bupivacaine was not found to be superior to the placebo intervention in reducing postoperative opioid requirements or improving other postoperative outcomes for patients undergoing a midline laparotomy. These results differed from previous reports evaluating the ultrasound-guided transversus abdominis plane block approach. Surgeon-administered transversus abdominis plane block should not be considered standard of care in postoperative multimodal analgesia. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Berntsen, S., et al. (2020). "Endometrial scratch injury with office hysteroscopy before IVF/ICSI: A randomised controlled trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 252: 112-117.
	Objective: Endometrial scratch injury (ESI) has been proposed to improve endometrial receptivity and thereby increase implantation rates in assisted reproductive technology (ART) treatment. ESI has been widely incorporated into clinical practice despite inconclusive evidence of its effect on reproductive outcomes. We aimed to assess pregnancy and live birth rates in subfertile women receiving ESI before IVF treatment in comparison to controls.; Study Design: This was a randomised controlled trial (RCT) with no blinding of participants, investigators or health care personnel. Women in ART treatment were allocated to either office hysteroscopy with ESI (ESI group) or no intervention (control group). In total 184 women in IVF/ICSI treatment with minimum one previous failed IVF/ICSI cycle, were included in the final analysis. The primary outcome was positive serum hCG (s-hCG). Secondary outcomes were ongoing pregnancy and live birth rate. Only per-protocol analyses were performed as all patients included at one centre had to be excluded. The trial is registered at ClinicalTrials.gov, NCT01743391.; Results: Our results showed a non-significant increase in positive s-hCG (OR 1.23, 95 % CI (0.65-2.33)), ongoing pregnancy (OR 1.52, 95 % CI (0.73-3.17)), and live birth rates (OR 1.69, 95 % CI (0.78-3.64)) per randomised woman between the ESI and the control group.; Conclusion: We observed no significant differences in positive s-hCG or other reproductive outcomes in the ESI vs. the control group. While the crude estimates of positive reproductive outcomes were higher in the ESI group, statistical significance was not reached, and the study was not powered to show smaller differences. However, data from this study will be re-evaluated in the context of an individual participant data meta-analysis (IPD-MA) of RCTs on ESI.; Competing Interests: Declaration of Competing Interest None. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Beroukhim, G. and B. Seifer David (2023). "Racial and Ethnic Disparities in Access to and Outcomes of Infertility Treatment and Assisted Reproductive Technology in the United States." Endocrinology and metabolism clinics of North America 52(4): 659-675.
	Infertility disproportionately affects the minority, non-White populace, with Black women having twofold higher odds than White women. Despite higher infertility rates, minority racial and ethnic groups access and utilize fertility care less frequently. Even once care is accessed, racial and ethnic disparities exist in infertility treatment and ART outcomes. Preliminary studies indicate that Asian and American Indian women have lower intrauterine insemination pregnancy rates. Many robust studies indicate significant racial and ethnic disparities in rates of clinical pregnancy, live birth, pregnancy loss, and obstetrical complications following in vitro fertilization, with lower favorable outcomes in Black, Asian, and Hispanic women. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Berry, S., et al. (2022). "Vitamin D deficiency and female infertility: A mechanism review examining the role of vitamin D in ovulatory dysfunction as a symptom of polycystic ovary syndrome." Journal of Reproductive Immunology 151: 103633.
	Around one billion people worldwide are understood to have sub-optimal levels of vitamin D. Polycystic ovary syndrome (PCOS) is reportedly a primary reason for female infertility. The main objective of this research was to understand the mechanistic role of vitamin D in the pathogenesis of female infertility in PCOS, specifically in relation to ovarian follicle development. In addition, the impact of vitamin D deficiency on oxidative stress and hormone production central to folliculogenesis was explored. The efficacy of vitamin D supplementation as an intervention to ameliorate ovulatory dysfunction in individuals with PCOS was evaluated. The systematic search strategy included three stages of search with a critical appraisal of the accepted papers: 1) other review papers; 2) primary mechanistic animal, in vitro and human studies; 3) primary intervention studies. In total, 80 papers were examined in detail and results analysed and evaluated. Mechanistic evidence indicated an association between vitamin D deficiency and impaired ovulatory function. Sub-optimal vitamin D levels were implicated in disrupted reproductive hormone balance, including overproduction of anti-mullerian hormone (AMH); accumulation of pro-inflammatory Advanced Glycation End Products (AGEs) and formation of Reactive Oxygen Species (ROS) in ovarian tissue, leading to abnormal folliculogenesis. Human intervention studies demonstrated the capability of vitamin D supplementation for restoring sufficient serum calcidiol (25(OH)D) levels in deficient individuals. Furthermore, the anti-inflammatory benefit of vitamin D was illustrated in studies examining the impact on oxidative stress. Co-supplementation with calcium was shown to benefit follicle growth; oxidative stress reduced with calcium, omega-3 fatty acid or probiotic co-supplementation. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bertarello, C., et al. (2024). "Efficacy and safety of Lactobacillus plantarum P 17630 strain soft vaginal capsule in vaginal candidiasis: a randomized non-inferiority clinical trial." European Review for Medical and Pharmacological Sciences 28(1): 384-391.
	OBJECTIVE: To investigate the non-inferiority of efficacy and tolerability of Lactobacillus plantarum P 17630 soft vaginal capsules compared to the antifungal therapy with miconazole nitrate 400 mg soft vaginal capsules in patients with symptomatic vulvovaginal infection due to Candida. PATIENTS AND METHODS: Adult women with vulvovaginal candidiasis were randomized to either L. plantarum P17630 100,000,000 CFU soft vaginal capsules by vaginal route each day for 3 or 6 consecutive days or miconazole nitrate 400 mg soft vaginal capsule. Visual Analog Scale (VAS) scores for vaginitis symptoms were used, and vaginal fluid interleukin 6 (IL6) was dosed. The study was registered in EudraCT database (code LPP17630-C-018; number: 2018-003095-12). RESULT(S): 200 patients were included in the study. The mean VAS scores for vaginitis symptoms were progressively reduced in both treatment groups at each visit, without significant difference between groups (p>0.05 for each symptom, at each time point). The efficacy of L. plantarum and the reference medicinal product was maintained at follow-up (day 21). The mean concentration of IL-6 decreased from visit 1 to visit 3 in both groups without a significant difference (p>0.05). No adverse events were reported. CONCLUSION(S):L.plantarumP17630100,000,000 CFU soft vaginal capsules are effective and safe for treating vaginal candidiasis without the concomitant use of an antifungal product, which rules out the risk of antimicrobic resistance. The long-term effect on vaginal microflora may add the possibility of reducing the risk of recurrences.Copyright © 2024 Verduci Editore s.r.l. All rights reserved.

Berton, D., et al. (2021). "Real-World Experience of Bevacizumab as First-Line Treatment for Ovarian Cancer: the GINECO ENCOURAGE Cohort of 468 French Patients." Frontiers in Pharmacology 12.
	Introduction: Bevacizumab‐containing therapy is considered a standard‐of‐care front‐line option for stage IIIB–IV ovarian cancer based on results of randomized phase 3 trials. The multicenter non‐interventional ENCOURAGE prospective cohort study assessed treatment administration and outcomes in the French real‐world setting. Patients and Methods: Eligible patients were aged ≥ 18 years with planned bevacizumab‐containing therapy for newly diagnosed ovarian cancer. The primary objective was to assess the safety profile of front‐line bevacizumab in routine clinical practice; secondary objectives were to describe patient characteristics, indications/contraindications for bevacizumab, treatment regimens and co‐medications, follow‐up and monitoring, progression‐free survival, and treatment at recurrence. In this non‐interventional study, treatment was administered as chosen by the investigator and participation in the trial had no influence on the management of the disease. Results: Of 1,290 patients screened between April 2013 and February 2015, 468 were eligible. Most patients (86%) received bevacizumab 15 mg/kg every 3 weeks or equivalent, typically with carboplatin (99%) and paclitaxel (98%). The median duration of bevacizumab was 12.2 (range 0–28, interquartile range 6.9–14.9) months; 8% of patients discontinued bevacizumab because of toxicity. The most common adverse events were hypertension (38% of patients), fatigue (35%), and bleeding (32%). There were no treatment‐related deaths. Most physicians (90%) reported blood pressure measurement immediately before each bevacizumab infusion and almost all (97%) reported monitoring for proteinuria before each bevacizumab infusion. Median progression‐free survival was 17.4 (95% CI, 16.4–19.1) months. The 3‐year overall survival rate was 62% (95% CI, 58–67%). The most commonly administered chemotherapies at recurrence were carboplatin and pegylated liposomal doxorubicin. Discussion: Clinical outcomes and tolerability with bevacizumab in this real‐life setting are consistent with randomized trial results, notwithstanding differences in the treated patient population and treatment schedule. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT01832415.

Bertuit, J., et al. (2020). "Interest of mobile and internet applications in the management of stress urinary incontinence in women. A systematic review." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 30(16): 1022-1037.
	
Bese, T., et al. (2023). "3-4 Cycles vs 6 Cycles NACT in Advanced Stage Epithelial Ovarian Cancer: Survival is not Determined by the Number of NACT Cycles." Chemotherapy.
	INTRODUCTION: The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) of patients who underwent interval cytoreductive surgery after 3-4 cycles or 6 cycles of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer patients. METHOD(S): Out of 219 patients with advanced epithelial ovarian cancer,123 patients received 3-4 cycles and 96 patients received 6 cycles of platinum-based NACT. Afterwards, laparotomy was performed for interval cytoreductive surgery. RESULT(S): No statistically significant difference was found for DFS and OS of the patients who received 3-4 cycles and those who received 6 cycles of NACT (HR:1.047,95.0%CI [0.779-1.407]; p:0.746 for DFS, and HR:1.181,95.0% CI [0.818-1.707]; p:0.368 for OS). Evaluating 123 patients who received 3-4 cycles of NACT;87 patients (70.7%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS compared to 36 patients(29.3%) with any residual tumor (HR:1.830,95.0% CI [1.194-2.806]; p:0.003 for DFS, and HR:1.946,95.0% CI [1.166-3.250]; p:0.009 for OS).96 patients who received 6 courses of NACT were evaluated;63 patients (65.6%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS than 33 patients (34.4%) with any residual tumor (HR:1.716,95.0% CI [1.092-2.697];p:0.010 for DFS, and HR:1.921,95.0%CI [1.125-3.282]; p:0.013 for OS). CONCLUSION(S): In patients with advanced ovarian cancer,there is no significant difference in DFS and OS between 3-4 cycles or 6 cycles of NACT.The most important factor determining survival is whether macroscopic residual tumor tissue remains after interval cytoreductive surgery following NACT.Copyright S. Karger AG, Basel.

Betof, A., et al. (2022). "TRIAL IN PROGRESS: A PHASE 1/2 OPEN-LABEL STUDY (IOV-GM1-201) OF TALEN-MEDIATED PD-1- INACTIVATED AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES (TIL; IOV-4001) IN PATIENTS WITH ADVANCED MELANOMA AND NSCLC." Journal for Immunotherapy of Cancer 10(Supplement 2): A814.
	Background Adoptive cell therapy with TIL has demonstrated efficacy in patients with advanced solid tumors, both as monotherapy in melanoma,1 NSCLC,2 and cervical cancer,3 and in combination with anti-PD-1 therapy in melanoma, head and neck cancer, and cervical cancer.4 IOV-4001 is a TALEN- mediated PDCD-1 knockout autologous TIL cell therapy product. Preclinical studies suggest that PD-1 inactivation by PDCD-1 gene knockout may enhance TIL cell therapy efficacy, with similar quality attributes and phenotypes to those of non-edited TIL.5 Methods This first-in-human phase 1/2, open-label, nonrandomized, multicenter study (NCT05361174; open to enrollment) will enroll ~53 adult patients. During the phase 1 portion, enrollment and dose level decisions will be based on emerging safety and tolerability data in a 28-day dose-limiting toxicity (DLT) observation period. Cohort 1 will include patients with unresectable/metastatic melanoma that has progressed during/within 12 weeks of last anti-PD-1/PD-L1 dose (patients must have also received a BRAF +/- MEK inhibitor if BRAF V600 mutation-positive). Cohort 2 will include patients with advanced NSCLC who have received <=3 prior therapies and whose disease progressed either: (1) during/within 12 weeks after last anti-PD-1/PD-L1 dose (patients without oncogene driver mutations) or (2) during/ after >=1 targeted therapy and either platinum doublet chemotherapy or during/within 12 weeks after last anti-PD-1/PDL1 dose (patients with oncogene-driven tumors). Patients must have ECOG performance status <=1, >=1 resectable lesion(s) (>=1.5 cm), >=1 remaining RECIST-measurable lesion(s) and recovered from prior surgery/anticancer treatment-related adverse events (AEs; grade <=1). IOV-4001 is generated from resected tumor in a centralized GMP process. The regimen includes nonmyeloablative lymphodepletion, IOV-4001 infusion, and a short course of high-dose IL-2. The primary endpoints of phases 1 and 2 are safety (DLTs and AEs) and objective response rate per RECIST v1.1, respectively. Secondary endpoints include complete response rate, duration of response, disease control rate, progressionfree survival, overall survival, feasibility, and additional safety.

Betül, S., et al. (2022). "Effect of Antioxidant Supplementation on Endometriosis Related Pain: A Systematic Review." PROSPERO International prospective register of systematic reviews.
	
Beucler, N., et al. (2021). "Brain metastases in endometrial cancer: A systematic review of the surgical prognostic factors." European Journal of Obstetrics, Gynecology, and Reproductive Biology 258: 240-252.
	Context: Although endometrial cancer is the fourth most common malignancy in women, dissemination to the brain is an exceptional event in the course of the disease. The aim of this review is to determine the important surgical prognostic factors for patients with endometrial cancer metastatic to the brain.; Materials and Methods: Report of two cases. Medline database was used to conduct a systematic literature review from inception to December 2020 looking for English-language articles focused on brain metastases from endometrial cancer.; Results: The research yielded 108 articles, among which 23 articles were retained for a total of 87 patients. Mean age was 60 years-old ±11 at the time of diagnosis of endometrial cancer, and most of the tumors were aggressive (grade 3) with an advanced-stage disease (FIGO III-IV). At the time of diagnosis of cerebral disease, a single brain metastasis (p < 0.0001) and no extra-cerebral metastatic site (p = 0.0011) were significant good prognostic factors for the median overall survival. Surgical excision of brain metastasis followed by radiotherapy provided the longest median overall survival compared to radiotherapy and/or chemotherapy, and surgery alone (respectively 32, 5.4 and 4.8 months, p < 0.0001). An age of 60-year-old or less was not associated with a better prognosis.; Conclusion: This review confirms that surgical excision followed by radiotherapy is a reliable option in patients with a single brain metastasis from endometrial cancer and no extra-cerebral metastatic site. This work could help to adapt the Graded Prognostic Assessment for brain metastases in endometrial cancer.; Competing Interests: Declaration of Competing Interest The authors report no declarations of interest. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Beygi, Z., et al. (2023). "An Overview of Reviews on the Effects of Acceptance and Commitment Therapy (ACT) on Depression and Anxiety." Iranian journal of psychiatry 18(2): 248-257.
	Objective: Emotional disturbances are the most common mental health problems in different populations and societies. We intend to provide the latest evidence related to the effectiveness of Acceptance and Commitment Therapy (ACT) on depression and anxiety by reviewing systematic review and meta-analysis studies published in the last three years. Method : PubMed and Google Scholar databases were systematically searched between January 1, 2019 and November 25, 2022 with relevant keywords for English systematic review and meta-analysis articles reviewing the utilization of ACT to reduce anxiety and depression symptoms. Results: 25 articles were included in our study: 14 systematic review and meta-analysis studies and 11 systematic reviews. These studies have investigated the effects of ACT on depression and anxiety in populations of children or adults, mental health patients, patients with different cancers or multiple sclerosis, people with audiological problems, parents or caregivers of children with mental or physical illnesses as well as normal people. Furthermore, they have examined the effects of ACT in individual, group, Internet, computerized, or combined delivery formats. Most of the reviewed studies reported significant effect sizes (small to large effect sizes) of ACT, regardless of the delivery method, compared to passive (placebo, waitlist) and active (treatment as usual and other psychological interventions except cognitive behavioral therapy (CBT)) controls for depression and anxiety. Conclusion: Recent literature mainly agrees on the small to moderate effect sizes of ACT on depression and anxiety symptoms in different populations.

Bezerra, L. O., et al. (2021). "Impact of Pelvic Floor Muscle Training Isolated and Associated with Game Therapy on Mixed Urinary Incontinence: A Randomized Controlled Trial." Games for health journal 10(1): 43-49.
	Objective: To verify whether pelvic floor muscle training (PFMT) associated with game therapy (GT) can potentiate improvements in PFM pressure, urinary loss, and perception of improvement in women with mixed urinary incontinence (MUI). Materials and Methods: A randomized and blinded trial was conducted with 32 women aged between 45 to 70 years presenting diagnosis of MUI. They were randomly divided into two groups: PFMT group and PFMT+GT group. Interventions occurred twice a week during 8 weeks. Primary outcome was PFM pressure, assessed by manometry, and secondary outcomes were 1-hour pad-test, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and patients global impression of improvement for incontinence (PGI-I). Two-way analysis of variance and post hoc Tukey analysis were performed. Results: Initially, no significant difference between groups was found in variables of age, body mass index, educational level, marital status, gynecological and obstetric variables, life habits, and sexual activity. Besides, at baseline clinical variables also showed similar results between groups for PFM pressure, 1-hour pad-test, and ICIQ-SF. Time-group interaction did not present statistically significant differences for PFM pressure (P = 0.56), 1-hour pad-test (P = 0.75), and ICIQ-SF (P = 0.30) in intergroup analysis. All women reported being "much better or better," considering the comparison of urinary complaints in the beginning and end of treatment. Conclusion: There were no statistically significant differences between groups for PFM pressure, 1-hour pad-test, and ICIQ-SF. However, both treatments proved to be effective for MUI symptoms. Perception of improvement was highly improved, according to women's report.

Bezier, E. (2021). "[Impact of biofeedback probes used in the self-rehabilitation of pelvic floor muscles in women with stress urinary incontinence. Literature review]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 31(7): 385-391.
	OBJECTIVE: The purpose of this review was to identify the evaluated effects of the use of biofeedback probes used in the self-rehabilitation of the pelvic floor muscles, on the muscle function, symptom severity, quality of life, and compliance/adherence to exercise for women with stress urinary incontinence. MATERIAL AND METHOD: A literature review was conducted in March 2020 on the PubMed, PEDro and Science Direct databases. RESULTS: A total of 3 randomised controlled trials (n=167 participants) were included and analysed. The different results found show significant improvements in muscle function with a percentage of 87.5% (P=0.003) of patients improved on the modified Oxford scale, as well as perineometry increasing from 23.06 to 32 (P=0.011). Symptom severity is also improved with a decrease in the number of pads and pad weight in the Pad Test (P<0.005). Concerning quality of life, significant improvements in the King's Health Questionnaire (KHQ) and the Visual Analogue Scale of Psychological Stress were found, with an improvement in the number of patients in each group at the end of the study (P<0.0005). No results showed a superiority of pelvic floor muscle training with a biofeedback probe compared to training alone. CONCLUSION: This review didn't provide real recommendations for the use of home biofeedback probes as an adjunct to pelvic floor muscle training in women with stress urinary incontinence. She suggests that the use of biofeedback probes wouldn't be more effective than training without them.

Bhaduri, M., et al. (2022). "Systematic review of pregnancy and renal outcomes for women with chronic kidney disease receiving assisted reproductive therapy." Journal of nephrology 35(9): 2227-2236.
	Background: As awareness around infertility is increasing among patients with chronic kidney disease (CKD), ever more of them are seeking Assisted Reproductive Technology (ART). Our aim was to perform a systematic review to describe obstetric and renal outcomes in women with CKD following ART.; Methods: The following databases were searched from 1946 to May 2021: (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) Embase and (4) MEDLINE.; Results: The database search identified 3520 records, of which 32 publications were suitable. A total of 84 fertility treatment cycles were analysed in 68 women. Median age at time of pregnancy was 32.5 years (IQR 30.0, 33.9 years). There were 60 clinical pregnancies resulting in 70 live births (including 16 multifetal births). Four women developed ovarian hyperstimulation syndrome which were associated with acute kidney injury. Hypertensive disorders complicated 26 pregnancies (38.3%), 24 (35.3%) pregnancies were preterm delivery, and low birth weight was present in 42.6% of pregnancies. Rates of live birth and miscarriage were similar for women with CKD requiring ART or having natural conception. However, more women with ART developed pre-eclampsia (p < 0.05) and had multifetal deliveries (p < 0.001), furthermore the babies were lower gestational ages (p < 0.001) and had lower birth weights (p < 0.001).; Conclusion: This systematic review represents the most comprehensive assessment of fertility outcomes in patients with CKD following ART. However, the high reported live birth rate is likely related to reporting bias. Patient selection remains crucial in order to maximise patient safety, screen for adverse events and optimise fertility outcomes. (© 2022. The Author(s).)

Bhat, A., et al. (2022). "Uterine externalization versus in situ repair of hysterotomy during cesarean delivery: a systematic review, equivalence meta-analysis, and trial sequential analysis." International journal of obstetric anesthesia 50: 103271.
	Background: Uterine positioning during hysterotomy repair is controversial, with both in situ and externalized approaches commonly performed. Despite many published trials, clinical equipoise remains. This meta-analysis and trial sequential analysis (TSA) summarizes studies comparing both techniques.; Methods: A systemic search for randomized controlled trials comparing in situ with externalized hysterotomy repair during cesarean delivery was performed. The primary outcomes were estimated blood loss (EBL) and surgical duration. Secondary outcomes were need for blood transfusion, incidence of endometritis, hospital length of stay, intra-operative hypotension, return of bowel function, intra-operative vomiting, intra-operative pain, and need for postoperative analgesia. Cochrane methodology was used to assess risk of bias. Data are presented as mean difference/standardized mean difference or odds ratio/risk difference with 95% confidence intervals (CI).; Results: Nineteen studies enrolling 20 739 patients were included. Estimated blood loss and surgical duration were equivalent between methods, with TSA confirming adequate information size for surgical duration but not EBL. In situ repair was associated with faster return of bowel function (MD -0.76 days; 95% CI -1.36 to -0.15; P=0.01) and a reduction in need for breakthrough postoperative analgesia (OR 0.44; 95% CI 0.28 to 0.68; P <0.01).; Conclusions: This analysis revealed equivalence between methods for EBL and surgical duration. While the small reduction in EBL with externalized repair was not clinically or statistically significant, TSA analysis revealed an unmet information size, suggesting a potentially inconclusive result. In situ repair may be associated with less breakthrough postoperative analgesia requirement and faster return of bowel function. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bhatt, A. and O. Glehen (2022). "Hyperthermic Intraperitoneal Chemotherapy in the Treatment Armamentarium of Epithelial Ovarian Cancer: Time to End the Dichotomy." Visceral medicine 38(2): 109-119.
	Background: Advanced epithelial ovarian cancer (EOC) is an incurable disease with over 75% of the patients developing recurrence in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for both first-line therapy and treatment of recurrence. In this article, we review the rationale and current evidence for performing HIPEC and the role of HIPEC in the light of targeted systemic therapies.; Summary: There are few randomized trials and several retrospective studies on the role of HIPEC in the management of EOC. A 12-month-overall survival (OS) benefit of the addition of HIPEC to interval cytoreductive surgery (CRS) was demonstrated in 1 randomized trial following which HIPEC has been included as a treatment option for this indication in several national/international guidelines. One retrospective propensity score-matched analysis showed a 16-month OS benefit of adding HIPEC to primary CRS. One randomized trial showed no benefit of the addition of carboplatin HIPEC to secondary CRS over secondary CRS alone. For patients undergoing primary CRS and secondary CRS for recurrence, the results of ongoing randomized trials are needed to define the role of HIPEC in these situations. All clinical trials have shown that the morbidity of HIPEC performed after CRS is acceptable. Along with the emergence of HIPEC as a promising surgical therapy, targeted therapies like bevacizumab and poly adenosine diphosphate-ribose polymerase inhibitors have been developed that have shown a survival benefit in selected patients. In principle, HIPEC and targeted therapies work in different ways and it is plausible to assume that their benefit could be additive, and their combination should be evaluated in clinical trials. The impact of prognostic factors like the disease extent, pathological response to systemic chemotherapy (SC), the histological subtype and molecular profile on the benefit of HIPEC, and targeted therapies has not been evaluated in clinical trials.; Key Messages: HIPEC is an important therapeutic strategy in the treatment of EOC. While its role in patients undergoing interval CRS has been established, the results of ongoing randomized trials are needed to define its benefit at other time points. The morbidity of HIPEC in addition to CRS is acceptable. More research is needed to define subgroups that benefit most from HIPEC based on the extent of disease, response to SC, histology, and molecular profile. The combination of HIPEC and maintenance therapies should be evaluated in well-designed randomized clinical trials that evaluate not just the survival benefit and morbidity but also the cost-effectiveness of each therapy.; Competing Interests: O. Glehen is a consultant for Gamida. A. Bhatt has no disclosures. The authors have no conflicts of interest to declare. (Copyright © 2022 by S. Karger AG, Basel.)

Bhattacharya, P., et al. (2023). "Delorme's vs. Altemeier's in the management of rectal procidentia: systematic review and meta-analysis." Langenbeck's archives of surgery 408(1): 454.
	Background: Rectal prolapse is a distressing condition for patients and no consensus exists on optimal surgical management. We compared outcomes of two common perineal operations (Delorme's and Altemeier's) used in the treatment of rectal prolapse.; Methods: A systematic search of multiple electronic databases was conducted. Peri- and post-operative outcomes following Delorme's and Altemeier's procedures were extracted. Primary outcomes included recurrence rate, anastomotic dehiscence rate and mortality rate. The secondary outcomes were total operative time, volume of blood loss, length of hospital stay and coloanal anastomotic stricture formation. Revman 5.3 was used to perform all statistical analysis.; Results: Ten studies with 605 patients were selected; 286 underwent Altemeier's procedure (standalone), 39 had Altemeier's with plasty (perineoplasty or levatoroplasty), and 280 had Delorme's. Recurrence rate [OR: 0.66; 95% CI [0.44-0.99], P = 0.05] was significantly lower and anastomotic dehiscence [RD: 0.05; 95% CI [0.00-0.09], P = 0.03] was significantly higher in the Altemeier's group. However, sub group analysis of Altemeier's with plasty failed to show significant differences in these outcomes compared with the Delorme's procedure. Length of hospital stay was significantly more following an Altemeier's operation compared with Delorme's [MD: 3.05, 95% CI [0.95 - 5.51], P = 0.004]. No significant difference was found in total operative time, intra-operative blood loss, coloanal anastomotic stricture formation and mortality rates between the two approaches.; Conclusions: A direct comparison of two common perineal procedures used in the treatment of rectal prolapse demonstrated that the Altemeier's approach was associated with better outcomes. Future, well-designed high quality RCTs with long-term follow up are needed to corroborate our findings. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bhide, A., et al. (2020). "Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infection and the potential role of the urinary microbiome." Post Reproductive Health 26(2): 87-90.
	Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections carry significant burden for those affected. As women enter the menopause, other factors may influence how these conditions manifest. The urinary microbiome has shown that the urine contains extensive numbers of bacteria. There is some evidence to suggest that it is altered depending on the menopausal state of the individual. It is possible that this alteration may go on to influence how the disease course of interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections runs in the post-menopausal group. The review will explore these two conditions and the potential role of the urinary microbiome.Copyright © The Author(s) 2020.

Bhide, A. A., et al. (2019). "The use of laser in urogynaecology." International Urogynecology Journal 30(5): 683-692.
	Introduction: The use of lasers in urogynaecology has increased in recent years. Their use has been described in pelvic organ prolapse, urinary incontinence and genito-urinary symptoms of menopause. The aim of this study was to review the published literature on CO2 and erbium:YAG laser use in urogynaecological conditions. Method(s): An extensive search of literature databases (PubMed, EMBASE) was performed for publications (full text and abstracts) written in English up to July 2018. Relevant trials were selected and analysed by an independent reviewer. Twenty-five studies were identified in total. Result(s): All studies were either prospective cohort or case-control studies. The results of individual studies indicate that both CO2 and erbium lasers are effective in treating urogynaecological conditions. Most studies use a vaginal approach with only two investigations of intraurethral application. Conclusion(s): The use of lasers to treat these conditions may seem appealing; however, the lack of good-quality evidence in the form of multi-centre randomised placebo-controlled trials is concerning. The safety and effectiveness of these laser devices have not been established. Use of lasers may lead to serious adverse events such as vaginal burns, scarring, dyspareunia and chronic pain. Randomised placebo-controlled trials in addition to formal evaluation of the laser devices are required before this treatment modality can be recommended.Copyright © 2018, The Author(s).

Bi, B., et al. (2022). "Bazedoxifene plus conjugated estrogens improve menopausal symptoms in postmenopausal women: a systematic review and meta-analysis." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(10): 813-821.
	Our aim is to evaluate the efficacy of bazedoxifene (BZA) plus conjugated estrogens (CE) on menopausal symptoms in postmenopausal women. A series of databases including PubMed, EMBASE, Medline, Web of science, China national knowledge internet and Wanfang database up to 31 October 2021 were searched, and randomized controlled trials (RCTs) of BZA/CE for menopausal symptoms were included. Seven RCTs involving 5431 patients were included in this study. Compared with placebo group, there were significantly reduce in daily number of hot flushes, daily number of moderate or severe hot flushes, the percentages of parabasal cells and the time to fall sleep when patients treated with BZA/CE. Besides, there were significant improvement in sleep disturbance and total MENQOL. However, no significant improvements in sleep adequacy were observed in the three groups. Furthermore, BZA 20 mg/CE 0.625 mg was more effective than BZA 20 mg/CE 0.45 mg in improving the menopausal symptoms. Therefore, both bazedoxifene 20 mg plus conjugated estrogens 0.45 mg and bazedoxifene 20 mg plus conjugated estrogens 0.625 mg could significantly improve the menopause-related symptoms and MENQOL in postmenopausal women, and the curative effects of BZA 20 mg/CE 0.625 mg were better than that of BZA 20 mg/CE 0.45 mg. These findings need to be further confirmed by more high-quality RCTs.

Bi, X., et al. (2022). "Modeling Pregnancy Outcomes through Sequentially Nested Regression Models." Journal of the American Statistical Association 117(538): 602-616.
	The polycystic ovary syndrome (PCOS) is a most common cause of infertility among women of reproductive age. Unfortunately, the etiology of PCOS is poorly understood. Large scale clinical trials for Pregnancy in Polycystic Ovary Syndrome (PPCOS) were conducted to evaluate the effectiveness of treatments. Ovulation, pregnancy, and live birth are three sequentially nested binary outcomes, typically analyzed separately. However, the separate models may lose power in detecting the treatment effects and influential variables for live birth, due to decreased sample sizes and unbalanced event counts. It has been a long-held hypothesis among the clinicians that some of the important variables for early pregnancy outcomes may continue their influence on live birth. To consider this possibility, we develop an ℓ 0 -norm based regularization method in favor of variables that have been identified from an earlier stage. Our approach explicitly bridges the connections across nested outcomes through computationally easy algorithms and enjoys theoretical guarantee of estimation and variable selection. By analyzing the PPCOS data, we successfully uncover the hidden influence of risk factors on live birth, which confirm clinical experience. Moreover, we provide novel infertility treatment recommendations (e.g., letrozole vs clomiphene citrate) for women with PCOS to improve their chances of live birth.

Bianca, P., et al. (2023). "Dydrogesterone as an alternative treatment in patients with endometriosis: a systematic review."
	
Bianchi, P., et al. (2022). "Utility of the Levonorgestrel-Releasing Intrauterine System in the Treatment of Abnormal Uterine Bleeding and Dysmenorrhea: A Narrative Review." Journal of Clinical Medicine 11(19): 5836.
	Introduction: We undertook a literature review of the use of levonorgestrel-releasing intrauterine devices when utilized for heavy menstrual bleeding and/or dysmenorrhea. Method(s): A narrative review of articles in the Scopus and Medline databases was conducted. Result(s): A number of options exist for the management of both abnormal uterine bleeding (AUB) and dysmenorrhea, and evidence is accumulating that the insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) represents a useful option for their long-term treatment. The idea of using a progestogen released in utero was initially conceived to achieve long-term contraception, but it was quickly found that these systems could be utilized for a number of therapeutic applications. The first device to be made commercially available, Progestasert, was withdrawn from the market because, in the event of contraceptive failure, it caused a disproportionate percentage of extrauterine pregnancies. On the other hand, the LNG-IUS continues to be successfully utilized in its various variants, releasing 20, 13, or 8 mug/day. These devices have a respective duration of action of 7 (possibly 8), 5, and 3 years, and there exist versions of frameless systems affixed to the myometrium of the uterine fundus. In the present review, following a brief description of the major causes of AUB and dysmenorrhea, the molecular bases for the use of the LNG-IUS are summarized. This is followed by a compendium of its use in AUB and dysmenorrhea, concluding that the insertion of the system improves the quality of life, reduces menstrual blood loss better than other medical therapies, and decreases the extent of dysmenorrhea and pelvic pain. In addition, there is no evidence of a significant difference in these outcomes when the use of the LNG-IUS was compared with improvements offered by endometrial ablation or hysterectomy. Possibly, the most important mechanism of action of the system consists of its ability to induce amenorrhea, which effectively eliminates heavy bleeding and dysmenorrhea. However, no method is ideal for every woman, and, in the case of the LNG-IUS, younger age and severe dysmenorrhea seem to be associated with a higher risk of discontinuation. Conclusion(s): The higher-dose LNG-IUS is a useful tool for HMB and dysmenorrhea in women of all ages. The low cost and ease of use make the LNG-IUS an attractive option, especially when contraception is also desired.Copyright © 2022 by the authors.

Bianchi, T., et al. (2023). "Radical Hysterectomy in Early-Stage Cervical Cancer: Abandoning the One-Fits-All Concept." Journal of Personalized Medicine 13(9).
	Two pillars in modern oncology are treatment personalization and the reduction in treatment-related morbidity. For decades, the one-fits-all concept of radical hysterectomy has been the cornerstone of early-stage cervical cancer surgical treatment. However, no agreement exists about the prevalent method of parametrial invasion, and the literature is conflicting regarding the extent of parametrectomy needed to achieve adequate surgical radicality. Therefore, authors started investigating if less radical surgery was feasible and oncologically safe in these patients. Two historical randomized controlled trials (RCTs) compared classical radical hysterectomy (RH) to modified RH and simple hysterectomy. Less radical surgery showed a drastic reduction in morbidity without jeopardizing oncological outcomes. However, given the high frequency of adjuvant radiotherapy, the real impact of reduced radicality could not be estimated. Subsequently, several retrospective studies investigated the chance of tailoring parametrectomy according to the tumor's characteristics. Parametrial involvement was shown to be negligible in early-stage low-risk cervical cancer. An observational prospective study and a phase II exploratory RCT have recently confirmed the feasibility and safety of simple hysterectomy in this subgroup of patients. The preliminary results of a large prospective RCT comparing simple vs. radical surgery for early-stage low-risk cervical cancer show strong probability of giving a final answer on this topic.

Bibault, J. E., et al. (2021). "Development and validation of a model to predict survival in colorectal cancer using a gradient-boosted machine." Gut 70(5): 884-889.
	OBJECTIVE: The success of treatment planning relies critically on our ability to predict the potential benefit of a therapy. In colorectal cancer (CRC), several nomograms are available to predict different outcomes based on the use of tumour specific features. Our objective is to provide an accurate and explainable prediction of the risk to die within 10 years after CRC diagnosis, by incorporating the tumour features and the patient medical and demographic information. DESIGN: In the prostate, lung, colorectal and ovarian cancer screening (PLCO) Trial, participants (n=154 900) were randomised to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. We selected patients who were diagnosed with CRC during the follow-up to train a gradient-boosted model to predict the risk to die within 10 years after CRC diagnosis. Using Shapley values, we determined the 20 most relevant features and provided explanation to prediction. RESULTS: During the follow-up, 2359 patients were diagnosed with CRC. Median follow-up was 16.8 years (14.4-18.9) for mortality. In total, 686 patients (29%) died from CRC during the follow-up. The dataset was randomly split into a training (n=1887) and a testing (n=472) dataset. The area under the receiver operating characteristic was 0.84 (±0.04) and accuracy was 0.83 (±0.04) with a 0.5 classification threshold. The model is available online for research use. CONCLUSIONS: We trained and validated a model with prospective data from a large multicentre cohort of patients. The model has high predictive performances at the individual scale. It could be used to discuss treatment strategies.

Bick, D., et al. (2022). "Antenatal preventative pelvic floor muscle exercise intervention led by midwives to reduce postnatal urinary incontinence (APPEAL): protocol for a feasibility and pilot cluster randomised controlled trial." Pilot and Feasibility Studies 8(1): 231.
	Background: Antenatal pelvic floor muscle exercises (PFME) in women without prior urinary incontinence (UI) are effective in reducing postnatal UI; however, UK midwives often do not provide advice and information to women on undertaking PFME, with evidence that among women who do receive advice, many do not perform PFME. Method(s): The primary aim of this feasibility and pilot cluster randomised controlled trial is to provide a potential assessment of the feasibility of undertaking a future definitive trial of a midwifery-led antenatal intervention to support women to perform PFME in pregnancy and reduce UI postnatally. Community midwifery teams in participating NHS sites comprise trial clusters (n = 17). Midwives in teams randomised to the intervention will be trained on how to teach PFME to women and how to support them in undertaking PFME in pregnancy. Women whose community midwifery teams are allocated to control will receive standard antenatal care only. All pregnant women who give birth over a pre-selected sample month who receive antenatal care from participating community midwifery teams (clusters) will be sent a questionnaire at 10-12 weeks postpartum (around 1400-1500 women). Process evaluation data will include interviews with midwives to assess if the intervention could be implemented as planned. Interviews with women in both trial arms will explore their experiences of support from midwives to perform PFME during pregnancy. Data will be stored securely at the Universities of Birmingham and Exeter. Results will be disseminated through publications aimed at maternity service users, clinicians, and academics and inform a potential definitive trial of effectiveness. The West Midlands-Edgbaston Research Ethics Committee approved the study protocol. Discussion(s): Trial outcomes will determine if criteria to progress to a definitive cluster trial are met. These include women's questionnaire return rates, prevalence of UI, and other health outcomes as reported by women at 10-12 weeks postpartum. Progress to a definitive trial however is likely to be prevented in the UK context by new perinatal pelvic health service, although this may be possible elsewhere. Trial registration: https://doi.org/10.1186/ISRCTN10833250. Registered 09/03/2020Copyright © 2022, The Author(s).

Bidhendi Yarandi, R., et al. (2019). "Metformin therapy before conception versus throughout the pregnancy and risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systemic review, meta-analysis and meta-regression." Diabetology & metabolic syndrome 11: 58.
	The results of studies that assessed the impact of metformin treatments on gestational diabetes mellitus (GDM) in patients with polycystic ovary syndrome (PCOS) are inconclusive. In addition, the impact of time and duration of metformin therapy for an optimum reduction of GDM has not been reported in these studies. This study aimed to summarize current knowledge regarding the effect of metformin-therapy before conception versus throughout pregnancy on the risk of GDM in women with PCOS. PubMed, Scopus, Google Scholar and ScienceDirect databases were searched to identify relevant studies. Both fixed and random effect models were used. Subgroup analyses were performed based on the on the study methodology. The association between the PCOS status and GDM was assessed using the univariate and multiple meta-regression analysis adjusted by the BMI and metformin therapy. Forty-eight of 1397 identified studies were included involving 5711 PCOS patients and 20,296 controls. Regardless of metformin therapy, the prevalence of GDM diagnosed in the second trimester among women with PCOS was significantly higher than healthy controls that was independent of obesity. Including all studies, the increased risk of GDM among women with PCOS, compared to healthy controls, disappeared after the adjustment of metformin-therapy (β = 0.08, 95% CI 0.04, 0.2; p = 0.624). By excluding observational studies as a source of bias, the prevalence of GDM among women with PCOS treated using metformin before conception till the end of pregnancy did not differ from treated just before conception (β = - 0.09, 95% CI - 0.2, 0.02; p = 0.092) or those without metformin therapy (β = - 0.05, 95% CI - 0.07, 0.04; p = 0.301). The results remained unchanged after the subgroup analysis based on the methodology of RCTs and non-RCTs studies. The main body of literature in the current meta-analysis was observational, which may be mixed with some sources of bias. Also, a lack of well-designed and high quality interventional studies means that the findings should be interpreted with cautious. In this respect, decisions regarding the continuation or discontinuation of metformin therapy in women with PCOS are somewhat arbitrary and can be made individually based on the patient's condition given the presence or absence of other GDM risk factors. Additional well-designed RCTs still need for precise recommendation.; Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Biehl, C., et al. (2019). "A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause." Menopause (New York, N.Y.) 26(4): 431-453.
	Objective: We updated a systematic review to evaluate the totality of evidence available for the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause (GSM) based on published randomized controlled trials.; Methods: We searched the Cochrane Library, Ovid, PubMed, Medline, Embase, and Clinicaltrials.gov for English-language articles from database inception to June 2018. Our search consolidated 2,086 potential sources to 53 full-text articles that were reviewed and found relevant to our systematic review.; Results: We identified 53 studies that met the inclusion criteria that evaluated the efficacy and safety of vaginal estrogen versus placebo or other hormone and nonhormone controls. Compared with placebo, all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of GSM, whereas some trials demonstrated superiority versus placebo in urogenital symptoms. No significant difference was observed between various dosages and dosage forms of vaginal estrogen products. Vaginal estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints. Unopposed vaginal estrogens seemed safe, although studies were not powered to detect a long-term estrogenic side effect.; Conclusion: Estrogen products were found to be clinically effective for the treatment of GSM with doses as low as 4 μg. Vaginal estrogen products seem to be safe with few adverse effects, although there is a lack of long-term controlled clinical trial safety data. This review supports the use of commercially available vaginal estrogen therapies as an effective and safe first-line therapy for the treatment of moderate-to-severe GSM.

Bieze, M., et al. (2024). "Spinal Cord Stimulation for Intractable Visceral Pain Originating from the Pelvic and Abdominal Region: A Narrative Review on a Possible New Indication for Patients with Therapy-Resistant Pain." Journal of Pain Research 17: 691-736.
	Aim: Visceral pain, characterized by pain that is diffuse and challenging to localize, occurs frequently and is difficult to treat. In cases where the pain becomes intractable despite optimal medical management, it can affect patients' Quality of Life (QoL). Spinal Cord Stimulation (SCS) has emerged as a potential solution for intractable visceral pain. Purpose(s): In this narrative review, we collected all evidence regarding the efficacy of SCS for visceral pain across various underlying conditions. Method(s): A comprehensive literature search was conducted in PubMed, Embase, and Web of Science in which articles published from October 1st, 1963 up to March 7th, 2023 were identified. Result(s): Seventy articles were included in this review of which most were retrospective cohort studies, case series and case reports. The studies, often with a small number of participants, reported on SCS for chronic pancreatitis, anorectal pain and bowel disorders, gynaecological diagnoses, visceral pelvic pain, urological disorders and finally general visceral pain. They found positive effects on pain and/or symptom relief, opioid consumption, anxiety and depression and QoL. Complications occurred frequently but were often minor and reversible. Conclusion(s): Better screening and selection criteria need to be established to optimally evaluate eligible patients who might benefit from SCS. A positive outcome of a sympathetic nerve block appears to be a potential indicator of SCS effectiveness. Additionally, women receiving SCS for endometriosis had a better outcome compared to other indications. Finally, SCS could also relief functional symptoms such as voiding problems and gastroparesis. Complications could often be resolved with revision surgery. Since SCS is expensive and not always covered by standard health insurance, the incorporation of cost-analyses is recommended. In order to establish a comprehensive treatment plan, including selection criteria for SCS, rigorous prospective, possibly randomized and controlled studies that are diagnosis-oriented, with substantial follow-up and adequate sample sizes, are needed.Copyright © 2024 Bieze et al. This work is published and licensed by Dove Medical Press Limited.

Bijlholt, M., et al. (2021). "The INTER-ACT E-Health Supported Lifestyle Intervention Improves Postpartum Food Intake and Eating Behavior, but Not Physical Activity and Sedentary Behavior-A Randomized Controlled Trial." Nutrients 13(4).
	Unhealthy postpartum lifestyle is related to long‐term adverse psychological, metabolic and cardiovascular health outcomes as well as to complications in the next pregnancy. Especially women with preceding excessive gestational weight gain are at risk. This paper aims to evaluate the effect of the postpartum phase of the INTER‐ACT randomized controlled trial (RCT) on food intake, eating behavior, physical activity and sedentary time at the end of the intervention (six months postpartum) and at six‐months follow‐up (12 months postpartum). The study population comprised women with excessive gestational weight gain in the preceding pregnancy. The lifestyle intervention combined a smartphone application with four face‐to‐face coaching sessions between six weeks and six months postpartum. After the intervention, restrained eating score was 1 point higher (95% CI 0.5, 1.5; p < 0.001), uncontrolled eating score was 1 point lower (95% CI −1.9, −0.2; p = 0.02) and energy intake was 69 kcal lower (95% CI −123, −15; p = 0.01) in the intervention group compared to the control group. The differences were no longer statistically significant at follow‐up. No significant effects on emotional eating, physical activity and sedentary behavior were found. In conclusion, the postpartum phase of the INTER‐ACT RCT was effective in improving nutrition‐related outcomes, however, these improvements could not be sustained at follow‐up. ClinicalTrials.gov identifier: NCT02989142.

Billon, E., et al. (2022). "Association of adrenal metastases with outcomes in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab in the GETUG-AFU-26 NIVOREN phase II trial." Journal of Clinical Oncology 40(6 SUPPL).
	Background: Glandular metastases (GMs) (adrenal, pancreas, thyroid, ovary, breast, or prostate) are rare in mccRCC. Several studies have observed significantly longer overall survival (OS) for GM patients treated with anti-angiogenic therapy. This study assesses outcomes from mccRCC treated with nivolumab with or without GMs. Method(s): The GETUG-AFU 26 NIVOREN, phase II trial assessed the activity and safety of nivolumab in pts with mccRCC who failed antiangiogenic therapies (NCT03013335). Pts were stratified in two subgroups according to the presence of at least one GM. Specific analyzes were performed for pancreatic and adrenal metastases. Primary endpoint was OS, secondary endpoint were progression free survival (PFS) and overall response rate (ORR). Result(s): Between February 2016 and July 2017, among 720 patients treated by nivolumab 217 patients had GM (151: adrenal and 86: pancreatic metastases). Clinical characteristics were comparable between the two subgroups except for IMDC poor subgroup vs 23.4%) for GM and non GM respectively. Median time between metastatic disease and nivolumab was 3.2 years (y) vs 2 y for GM and non GM respectively and 2.8 vs 2.1 y with or without adrenal metastasis. There was no statistical difference in outcomes between pts with or without GMs. However, pts with adrenal metastases had worse OS (12-months survival: 64% vs 71.1%; HR 1.51 (1.19-1.92)); shorter PFS (6-months survival: 27.2% vs 36.6%; HR 1.29 (1.07-1.57)) and lower ORR (12.5% [7.6%; 19.0%] vs 23.2% [19.8%; 27.0%]; p = 0.005) than non-adrenal metastases. Conversely, patients with pancreatic metastases had significantly longer overall survival (12-months survival: 82.3% vs 67.9%; HR 0.59 (0.40-0.85)) in univariate analysis compared to non-pancreatic metastases. In multivariate analysis, only adrenal metastasis remained associated with dismal prognosis (Table). Conclusion(s): Adrenal metastasis is an independent poor prognostic factor for response and survival in the GETUG-AFU 26 NIVOREN phase II trial. Limited activity with nivolumab is observed for patients with adrenal metastases from mccRCC without difference with previous anti angiogenic therapy. Molecular characterization could help to identify the angiogenic profile of adrenal metastases.

Bina, R. (2020). "Predictors of postpartum depression service use: A theory-informed, integrative systematic review." Women and birth : journal of the Australian College of Midwives 33(1): e24-e32.
	Problem: Postpartum depression affects many women globally, yet rates of treatment use are low. A comprehensive view of factors associated with treatment use, from women's and providers' perspectives, based on a theoretical model is lacking.; Background: Several studies examined various factors associated with postpartum depression service use; however, each study focused on a small number of factors.; Aim: This study describes a systematic literature review based on the Behavioral Model of Health Service Use. The purpose of this article is to review and synthesize the available literature regarding factors associated with women's mental health service use for postpartum depression from women's and healthcare providers' perspectives, and provide a comprehensive integrative view of the subject.; Methods: Three electronic databases were searched, and 35 studies published up to 2018 in English language journals met inclusion criteria for review. Factors associated with postpartum depression service use were classified according to the Behavioral Model of Health Service Use's constructs.; Findings: Service use for postpartum depression is a function of a woman's predisposition to use mental health services; individual, familial, and communal factors which enable or pose barriers to use of mental health services; and the woman's perceived or evaluated need for treatment. In addition, societal determinants impact the woman's decision to seek help directly or through impacting the health and mental health care service system's resources and organization.; Conclusion: This review illustrates key factors for researchers and practitioners to consider when treating postpartum women and developing interventions to enhance postpartum depression treatment use. (Copyright © 2019 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Bio, B. (2023). Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy, in Subjects With Tumors With Oncogene Amplifications.
	No Results Available Drug: BBI-355 Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355|Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-355|Maximum observed plasma concentration (Cmax) of BBI-355|Trough observed plasma concentration (Ctrough) of BBI-355|Time to Cmax (Tmax) of BBI-355|Area under the concentration time curve (AUC) of BBI-355|Anti-tumor activity of BBI-355 All Phase 1 47 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment BBI-355-101 January 31, 2026

Bio, I. (2022). ITIL-306 in Advanced Solid Tumors.
	No Results Available Biological: ITIL-306 Frequency and severity of ITIL-306 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (AESI)|Objective response rate (ORR)|Duration of response (DOR)|Progression-free survival (PFS)|Overall Survival (OS) All Phase 1 51 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ITIL-306-201 November 2039

BioClin, B. V., et al. (2021). Multi-Gyn ActiGel Plus for Treatment of Bacterial Vaginosis.
	No Results Available Device: vaginal gel Clinical cure rate of BV at 3 weeks after start of treatment (end-of treatment visit; Visit 2).|Microbiological cure rate (based on Nugent score <4) at Visit 2 Female Not Applicable 200 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment MGAP BV 001 December 1, 2024

Biologics, A. G. L. and GlaxoSmithKline (2023). Assessing the Safety, Immune Response, and Early Efficacy of a Candida Vaccine in Women With Recurrent Vulvovaginal Candidiasis: A Randomized Controlled Study.
	No Results Available Biological: Vaccine - Percentage of participants with solicited AEs at the administration site during the 7-day follow-up period (day of administration and 6 following days) after each dose, in the Candi5V arms and the placebo arm.|- Percentage of participants with each solicited systemic AE during the 7-day follow-up period (day of administration and 6 following days) after each dose, in the Candi5V arms and the placebo arm.|- Percentage of participants with unsolicited AEs during the 28-day follow-up period (day of administration and 27 following days) after each dose, in the Candi5V arms and the placebo arm.|- Percentage of participants with SAEs from the first dose to study end in the Candi5V arms and the placebo arm.|- Percentage of participants with medically relevant AEs from the first dose to study end.|- Percentage of participants with AEs leading to withdrawal from the study or to the withholding of further study intervention administration, during their entire study participation, in the Candi5V arms and the placebo arm.|- Percentage of participants with haematological and biochemical laboratory abnormalities at 7-days post-dose compared to pre-dose values (V3 vs V2, V7 vs V6) in the Candi5V arms and the placebo arm.|- Percentage of participants with AESIs (e.g., pIMDs, vulvovaginal candidiasis, extravaginal candidiasis or systemic fungal infection) from the first dose to study end in the Candi5V arms and the placebo arm.|- Evaluation of geometric mean titers (GMTs) for serum IgG against the five Candida antigens included in Candi5V, between baseline and post-vaccination samples collected at V8 (i.e., 28 days after the second vaccination).|- Evaluation of geometric mean titers (GMTs) for serum IgG against the five Candida antigens included in Candi5V, between baseline and post-vaccination samples collected at V5, in the Candi5V arms and the placebo arm.|- Evaluation of geometric mean ratios (GMRs) for serum IgG against the five Candida antigens included in Candi5V, between baseline and post-vaccination (fold increase) on samples collected at V5 and V8, in the Candi5V arms and the placebo arm.|- Percentage of participants in the Candi5V arms and the placebo arm achieving at least a four-fold rise (seroconversion) in the GMT of serum IgG against the Candi5V antigens at V5 and V8, compared to baseline.|- Evaluation of geometric mean titers (GMTs) for serum IgA against the five Candida antigens included in Candi5V, between baseline and post-vaccination samples collected at V8, in the Candi5V arms and the placebo arm.|- Evaluation of GMRs for serum IgA against the five Candida antigens included in Candi5V between baseline and post-vaccination (fold increase) on samples collected at V8, in the Candi5V arms and the placebo arm.|- Percentage of participants in the Candi5V arms and the placebo arm achieving at least a four-fold rise (seroconversion) in the GMT of serum IgA against the Candi5V antigens at V8, compared to baseline.|- Evaluation of GMTs for vaginal swab IgG and IgA against the five Candida antigens included in Candi5V between baseline and post-vaccination on samples collected at V8, in the Candi5V arms and the placebo arm.|- Evaluation of GMRs for vaginal swab IgG and IgA against the five Candida antigens included in Candi5V between baseline and post-vaccination on samples collected at V8, in the Candi5V arms and the placebo arm.|- Percentage of participants in the Candi5V arms and the placebo arm achieving at least a four-fold rise (seroconversion) in the GMT of vaginal swab IgG and IgA against the Candida antigens included in Candi5V at V8 compared to baseline.|- Incidence rates of VVC cases during the 12 months post 2nd vaccination, in the Candi5V arms and the placebo arm. For the purpose of the case definition, only the first confirmed VVC infection will be considered.|- Incidence rates of VVC cases from 28 days after 1st vaccination until end of the study, in the Candi5V arms and the placebo arm. For the purpose of the case definition, only the first confirmed VVC infection will be consid Female Phase 1|Phase 2 251 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Prevention Candi5V01|2023-507527-28-00 December 31, 2025

BioNTech, S. E. (2022). Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT141 in Patients With Unresectable or Metastatic CLDN18.2-positive Gastric, Pancreatic, Ovarian and Biliary Tract Tumors.
	No Results Available Biological: BNT141|Drug: Nab-paclitaxel|Drug: Gemcitabine Occurrence of treatment-emergent adverse events (TEAEs) within a patient including Grade ≥ 3, serious, fatal TEAE by relationship|Occurrence of dose reductions and discontinuation of BNT141 due to TEAEs throughout the study and up to 60 days after last subject last treatment|Occurrence of dose-limiting toxicities (DLTs) within a patient during the DLT evaluation period|BNT141 pharmacokinetic: Area under the concentration time curve (AUC)|BNT141 pharmacokinetic: Clearance (CL)|BNT141 pharmacokinetic: Volume of distribution (VD)|BNT141 pharmacokinetic: Maximum concentration of the drug (Cmax)|BNT141 pharmacokinetic: Time to maximum concentration (Tmax)|BNT141 pharmacokinetic: Concentration prior to next dose (Ctrough)|BNT141 pharmacokinetic: Elimination half-life (t half)|BNT141 - Objective response rate (ORR)|BNT141 - Disease control rate (DCR)|BNT141 - Duration of response (DOR) All Phase 1|Phase 2 13 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment BNT141-01|2022-001843-25 July 24, 2023

Biosciences, S. (2022). A Study of Safety and Efficacy of Tildacerfont in Females With Polycystic Ovary Syndrome and Elevated Adrenal Androgens.
	No Results Available Drug: Tildacerfont|Drug: Placebo DHEAS level|Reduction in DHEAS|Normalization of DHEAS|Number of subjects with TEAE as assessed by CTCAE Version 5 Female Phase 2 27 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment SPR001-210 August 31, 2023

Birmingham University, o. (2021). Impact of 11-oxygenated Androgens on Metabolic Dysfunction of Women With Polycystic Ovary Syndrome.
	No Results Available Drug: oral androgen challenge with dehydroepiandrosterone (DHEA) The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline height|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline weight|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline body mass index (BMI)|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline waist circumference|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline blood pressure|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline urea & electrolytes|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline liver function test|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline haemoglobin|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline white cell and platelet count|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline lipid profile|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline glucose|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline glycated haemoglobin|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline thyroid function test|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline Dehydroepiandrosterone (DHEAS)|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline androstenedione|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline testosterone|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline sex hormone binding globulin|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline 17-hydroxyprogesterone|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline prolactin|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline Follicle-stimulating hormone|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline luteinizing hormone|overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline oestradiol|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-understanding steroidal activity in peripheral blood mononuclear cells.|The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study th Female Not Applicable 100 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Other RG_19-038 May 30, 2025

Birmingham University of Alabama, a. (2022). Topical Vaginal Estrogen for Postpartum Obstetric Anal Sphincter Injury Recovery.
	No Results Available Drug: Estradiol 0.01% Vag Cream|Drug: Placebo vaginal cream sexual dysfunction symptom severity|Urinary incontinence|Anal incontinence Female Phase 4 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment 300008970 July 1, 2026

Birowo, P., et al. (2020). "Efficacy and safety of extracorporeal shockwave therapy for the treatment of chronic non-bacterial prostatitis: A systematic review and meta-analysis." PloS One 15(12): e0244295.
	Purpose: Chronic pelvic pain syndrome (CPPS) is one of the most common outpatient urological diagnoses, and its incidence is increasing. Extracorporeal shockwave therapy (ESWT) has been suggested for relieving local perineal symptoms associated with chronic prostatitis/CPPS. Despite several treatment methods, no causal or standardized treatment is available for CPPS. This study aimed to investigate the efficacy and safety profile of ESWT for the treatment of chronic non-bacterial prostatitis.; Materials and Methods: Studies were collected using four search engines (Pubmed, Cochrane, ScienceDirect, and EBSCOHost), on May 16, 2020; and assessed based on predetermined inclusion and exclusion criteria. Two reviewers performed study selection. Studies were then analyzed using Review Manager 5.3 for the meta-analysis.; Results: Seventy-four publications were initially retrieved, and three studies were considered for both qualitative and quantitative analyses. From these studies, we found that the use of ESWT was significantly associated with decreased pain domain (mean difference: -3.93; 95% confidence interval [CI] -5.13, -2.73; p<0.001), improved urinary score (mean difference: -1.79; 95% CI -2.38, -1.21; p<0.001), improved quality of life (mean difference: -1.71; 95% CI -2.12, -1.31; p<0.001), and improved National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score (mean difference: -5.45; 95% CI -5.74, -5.16; p<0.001) after 12 weeks of treatment.; Conclusion: ESWT is efficacious and safe in reducing pain and improving urinary condition, NIH-CPSI score, and quality of life in patients with chronic non-bacterial prostatitis.; Competing Interests: No authors have competing interests.

Bisch, S., et al. (2021). "Efficacy of pre-operative pharmacologic thromboprophylaxis on incidence of venous thromboembolism following major gynecologic and gynecologic oncology surgery: A systematic review and meta-analysis." International Journal of Gynecological Cancer 31(2): 257-264.
	Introduction Venous thromboembolism remains a significant complication following major gynecologic surgery. Evidence is lacking on whether it is beneficial to give pharmacologic thromboprophylaxis pre-operatively. The aim of this meta-analysis was to assess the role of pre-operative pharmacologic thromboprophylaxis in preventing post-operative venous thromboembolism. Methods PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials were searched to find randomized controlled, cohort, and case-control trials comparing pre-operative pharmacologic thromboprophylaxis to no prophylaxis, mechanical prophylaxis, or only post-operative pharmacologic thromboprophylaxis for open and minimally invasive major gynecologic surgery (benign and malignant conditions). Two authors independently assessed abstracts, full-text articles, and methodological quality. Data were extracted and pooled using ORs for random effects meta-analysis. Heterogeneity was explored using forest plots, Q-statistic, and I 2 statistics. Planned subgroup analysis of use of sequential compression devices, equivalent versus non-equivalent post-operative prophylaxis, cancer diagnosis, and methodological quality were performed. Results Some 503 unique studies were found, and 16 studies (28 806 patients) were included in the systematic review. Twelve studies (14 273 patients) were included in the meta-analysis. The OR for incidence of post-operative venous thromboembolism was 0.59 (95% CI 0.39, 0.89), favoring pre-operative pharmacologic thromboembolism prophylaxis compared with no pre-operative pharmacologic prophylaxis (Q=13.80, I 2 =20.30). In studies where post-operative care was equivalent between groups, the OR for venous thromboembolism was 0.56 (95% CI 0.22, 1.40). Pre-operative pharmacologic prophylaxis demonstrated greatest benefit when utilized with both intra-operative and post-operative sequential compression devices (OR 0.43, 95% CI 0.30, 0.64) compared with when no sequential compression devices were utilized (OR 1.27, 95% CI 0.63, 2.56). When looking at only studies determined to be of high quality, the results no longer reached significance (OR 0.73, 95% CI 0.36, 1.46). Conclusions Pre-operative pharmacologic thromboprophylaxis decreases the odds of venous thromboembolism in the peri-operative period for major gynecologic oncology surgery by approximately 40%. It remains unclear whether this benefit is present in benign and minor procedures. Adequately powered studies are needed.Copyright © 2021 BMJ Publishing Group. All rights reserved.

Bisch, S. P., et al. (2021). "Outcomes of enhanced recovery after surgery (ERAS) in gynecologic oncology - A systematic review and meta-analysis." Gynecologic Oncology 161(1): 46-55.
	Objective: To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology.; Methods: A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost.; Results: A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2-2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55-0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64-0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23-1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544).; Conclusions: ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.; Competing Interests: Declaration of Competing Interest Dr. Nelson reports advisory fees from Abbott, outside the submitted work; and Secretary of the ERAS® Society. Dr. Meyer reports research support from AstraZeneca and consulting for GlaxoSmithKline outside the submitted work. The remaining authors declare no conflict of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bisht, N., et al. (2021). "A Comparative Study of Two Protocols of Concurrent Chemotherapy with External Beam Radiotherapy in Treatment of Locally Advanced Cervical Cancer: Cisplatin Versus Cisplatin Plus Capecitabine Combination." Indian Journal of Gynecologic Oncology 19(1): 18.
	Introduction: Cervical carcinoma is one of the commonest cancers affecting women in the low- and middle-income countries. The standard treatment of locally advanced cases by external beam radiotherapy (EBRT) along with single-agent cisplatin-based concurrent chemotherapy is effective, but rates of treatment failure and recurrence remain high. There exists a need to augment the treatment protocol. One modality to do that is by addition of another radiosensitizer/chemotherapeutic agent. Method(s): In total, 40 women with histologically proven locally advanced cervical cancer were included in the study. The first 20 (Arm 1) were treated with EBRT along with concurrent cisplatin at 40 mg/m2 (maximum 70 mg). The next 20 patients (Arm 2) received the same treatment but also received oral capecitabine 460 mg/m2 during EBRT. Treatment-related toxicity and disease response rates at 6 months were compared in the two arms. Overall survival at 5 years of patients in the two arms was also compared. Result(s): During treatment, 40% of patients in Arm 1 developed anemia compared to 45% in Arm 2. In total, 5% patients in Arm 1 and 10% in Arm 2 developed grade 2 leucopenia. A higher incidence of proctitis and diarrhea was seen in Arm 2 (30%) than in Arm 1 (15%). The grade of proctitis and diarrhea was also higher in Arm 2 than in Arm 1. None of the patients developed hand-foot syndrome. All the complications were managed symptomatically and did not cause significant treatment break in either treatment arms except in one patient in Arm 2. At 6-month follow-up, four patients (20%) in both arms had residual or progressive disease. At the end of 5 years, the mean overall survival in the two Arms 1 and 2 was 47.9 and 48.4 months, respectively. Conclusion(s): The addition of capecitabine to standard concurrent chemoradiotherapy with cisplatin for locally advanced cervical cancer is well tolerated even on an OPD basis though there is increased incidence of acute proctitis and diarrhea with this combination. No difference in treatment efficacy or improvement in survival between the two protocols was seen in our study though this may have been influenced by the small sample size and short period of follow-up of our study. We recommend a phase II/III study to further evaluate the efficacy and tolerability of this regimen.Copyright © 2021, Association of Gynecologic Oncologists of India.

Bisson Jonathan, I., et al. (2019). "The international society for traumatic stress studies new guidelines for the prevention and treatment of posttraumatic stress disorder: Methodology and development process." Journal of Traumatic Stress 32(4): 475-483.
	Over the last two decades, treatment guidelines have become major aids in the delivery of evidence‐based care and improvement of clinical outcomes. The International Society for Traumatic Stress Studies (ISTSS) produced the first guidelines for the prevention and treatment of posttraumatic stress disorder (PTSD) in 2000 and published its latest recommendations, along with position papers on complex PTSD (CPTSD), in November 2018. A rigorous methodology was developed and followed; scoping questions were posed, systematic reviews were undertaken, and 361 randomized controlled trials were included according to the a priori agreed inclusion criteria. In total, 208 meta‐analyses were conducted and used to generate 125 recommendations (101 for adults and 24 for children and adolescents) for specific prevention and treatment interventions, using an agreed definition of clinical importance and recommendation setting algorithm. There were eight strong, eight standard, five low effect, 26 emerging evidence, and 78 insufficient evidence to recommend recommendations. The inclusion of separate scoping questions on treatments for complex presentations of PTSD was considered but decided against due to definitional issues and the virtual absence of studies specifically designed to clearly answer possible scoping questions in this area. Narrative reviews were undertaken and position papers prepared (one for adults and one for children and adolescents) to consider the current issues around CPTSD and make recommendations to facilitate further research. This paper describes the methodology and results of the ISTSS Guideline process and considers the interpretation and implementation of the recommendations. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

Bissonnette, F., et al. (2021). "Individualized ovarian stimulation for in vitro fertilization: a multicenter, open label, exploratory study with a mixed protocol of follitropin delta and highly purified human menopausal gonadotropin." Fertility and Sterility 115(4): 991-1000.
	Objective: To evaluate the safety profile and the number of usable blastocysts on day 5 and on day 6 after treatment with an individualized dosing regimen of a follitropin delta and highly purified human menopausal gonadotropin (HP-hMG) for controlled ovarian stimulation.; Design: Multicenter, open label, exploratory study.; Setting: Reproductive medicine clinics.; Patient(s): A total of 110 patients (aged 18-40 years).; Intervention(s): Follitropin delta coadministered with HP-hMG, with follitropin delta dose fixed according to an established algorithm and HP-hMG dose at 75 IU when the follitropin delta starting dosage was <12 μg; 150 IU when follitropin delta dosage was 12 μg and weight <100 kg, and 225 IU when follitropin delta dosage was 12 μg and weight ≥100 kg (dosage adjustments confined to HP-hMG only).; Main Outcome Measure(s): Mean number of good-quality blastocysts obtained at day 5 and day 6 as well as the proportion of women with ovarian hyperstimulation syndrome (OHSS).; Result(s): A cohort study was compared with the follitropin delta group from the Evidence-based Stimulation Trial with Human Recombinant Follicle-Stimulating Hormone in Europe and Rest of World 1 (ESTHER-1) study. Even when stratified by age, a statistically significantly higher mean in the number of oocytes retrieved and number of good-quality blastocysts was observed in this study compared with the ESTHER-1 trial in which follitropin delta was used alone. The rate of patients triggered with a gonadotropin-releasing hormone agonist was statistically significantly higher in our Menopur and Rekovelle Combined Study (MARCS) cohort (43%) when compared with the rates reported in the follitropin delta cohort in the ESTHER-1 study (2.3%). Incidence of any grade of OHSS was 9.3% in the present study compared to 2.6% in follitropin delta group from ESTHER-1 trial. No cases of moderate or severe OHSS were observed in our study compared with 1.4% in the follitropin delta group of ESTHER-1.; Conclusion(s): Optimizing the ovarian response during in vitro fertilization employing a mixed protocol of individualized dosing of follitropin delta and HP-hMG resulted in a statistically significant number of usable blastocysts on days 5 and 6 with an increased risk of mild OHSS, which did not require medical intervention or hospitalization.; Clinical Trial Registration Number: NCT03483545. (Copyright © 2020. Published by Elsevier Inc.)

Bittelbrunn Cleima, C., et al. (2023). "Pelvic floor physical therapy and mindfulness: approaches for chronic pelvic pain in women-a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 307(3): 663-672.
	Purpose: Chronic pelvic pain (CPP) in women is a complex syndrome and symptoms are associated with sexual dysfunction, musculoskeletal and myofascial disorders, and comorbid psychiatric disorders. Its widespread prevalence results in substantial expense due to therapy and lost productivity, and it is perhaps one of the most urgent and neglected medical needs. This systematic review and meta-analysis aimed to estimate the role of mindfulness and pelvic floor physical therapy (PFPT) in the treatment or management of women with CPP.; Methods: This systematic review (CRD42020204987) searched for relevant publications between January 2000 and November 2020 on MEDLINE/PubMed, Web of Science, One File GALE, and Technology Research databases using the following search terms: chronic pelvic pain, pelvic floor physical therapy/physiotherapy, mindfulness, and their variants. Risk of bias and quality of evidence were evaluated.; Results: Seven clinical trials (n = 279) were included in the review, and five in the meta-analysis (n = 225). For the pain outcome and its catastrophizing, there was a statistical difference for the Pain Catastrophizing Scale after treatment and during follow-up with mindfulness and PFPT (MD = - 3.82 [- 6.97, - 0.68], p = 0.01, and MD = - 4.49 [- 7.61, - 1.37], p = 0.00, respectively). Sexual function, assessed by the female sexual function index, differed significantly during follow-up between PFPT and mindfulness (MD = - 0.72 [- 1.38, - 0.05], p = 0.03).; Conclusion: The small number of studies applying both PFPT and mindfulness to CPP suggests that a multidisciplinary approach is required to treat women with CPP, and further studies involving these therapeutic techniques throughout the CPP cycle are needed. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bitton Rachel, R., et al. (2023). "What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers." European radiology 33(11): 7360-7370.
	Objective: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids.; Materials and Methods: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes.; Results: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01).; Conclusion: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother.; Clinical Relevance Statement: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid.; Trial Registration: Clinical trial ID: NCT01285960.; Key Points: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment. (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Bizzarri, N., et al. (2024). "External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis." European Journal of Surgical Oncology 50(4): 108013.
	Objective: We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. Method(s): We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). Result(s): We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade>=3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). Conclusion(s): No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments.Copyright © 2024 The Authors

Bizzarri, N., et al. (2023). "Radiomics systematic review in cervical cancer: gynecological oncologists' perspective." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(10): 1522-1541.
	Objective: Radiomics is the process of extracting quantitative features from radiological images, and represents a relatively new field in gynecological cancers. Cervical cancer has been the most studied gynecological tumor for what concerns radiomics analysis. The aim of this study was to report on the clinical applications of radiomics combined and/or compared with clinical-pathological variables in patients with cervical cancer.; Methods: A systematic review of the literature from inception to February 2023 was performed, including studies on cervical cancer analysing a predictive/prognostic radiomics model, which was combined and/or compared with a radiological or a clinical-pathological model.; Results: A total of 57 of 334 (17.1%) screened studies met inclusion criteria. The majority of studies used magnetic resonance imaging (MRI), but positron emission tomography (PET)/computed tomography (CT) scan, CT scan, and ultrasound scan also underwent radiomics analysis. In apparent early-stage disease, the majority of studies (16/27, 59.3%) analysed the role of radiomics signature in predicting lymph node metastasis; six (22.2%) investigated the prediction of radiomics to detect lymphovascular space involvement, one (3.7%) investigated depth of stromal infiltration, and one investigated (3.7%) parametrial infiltration. Survival prediction was evaluated both in early-stage and locally advanced settings. No study focused on the application of radiomics in metastatic or recurrent disease.; Conclusion: Radiomics signatures were predictive of pathological and oncological outcomes, particularly if combined with clinical variables. These may be integrated in a model using different clinical-pathological and translational characteristics, with the aim to tailor and personalize the treatment of each patient with cervical cancer.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Bjarkadottir, B. D., et al. (2021). "Analysing culture methods of frozen human ovarian tissue to improve follicle survival." Reproduction & fertility 2(1): 59-68.
	In vitro follicle growth is a potential fertility preservation method for patients for whom current methods are contraindicated. Currently, this method has only been successful using fresh ovarian tissue. Since many patients who may benefit from this treatment currently have cryopreserved ovarian tissue in storage, optimising in vitro follicle growth (IVG) for cryopreserved-thawed tissue is critical. This study sought to improve the first step of IVG by comparing different short-term culture systems for cryopreserved-thawed human ovarian tissue, in order to yield a higher number of healthy multilayer follicles. We compared two commonly used culture media (αMEM and McCoy's 5A), and three plate conditions (300 µL, 1 mL on a polycarbonate membrane and 1 mL in a gas-permeable plate) on the health and development of follicles after 6 days of culture. A total of 5797 follicles from three post-pubertal patients (aged 21.3 ± 2.3 years) were analysed across six different culture conditions and non-cultured control. All culture systems supported follicle development and there was no difference in developmental progression between the different conditions tested. Differences in follicle morphology were evident with follicles cultured in low volume conditions having significantly greater odds of being graded as morphologically normal compared to other conditions. Furthermore, culture in a low volume of αMEM resulted in the highest proportion of morphologically normal primary and multilayer follicles (23.8% compared to 6.3-19.9% depending on condition). We, therefore, recommend culturing cryopreserved human ovarian tissue in a low volume of αMEM to support follicle health and development. LAY SUMMARY: Ovaries contain a large number of follicles, each containing an immature egg and other important cells. Cancer treatments can lead to long-lasting negative side effects to the ovaries including the destruction of follicles, resulting in infertility. One strategy to preserve fertility is freezing of ovaries or ovarian tissue in girls and women undergoing cancer treatment. The long-term aim is to thaw and grow their ovarian tissue in the laboratory to obtain mature eggs, which can then be fertilised. In this study, we compared six different methods of growing previously frozen human ovarian tissue in order to best support follicle growth and health. We found that using the lowest amount of αMEM medium (a specific type of nutrient-rich growth solution) resulted in the highest proportion of healthy follicles. Improving the methods used to grow ovarian tissue, particularly frozen tissue, is important for future fertility preservation.

Bjersand, K., et al. (2022). "Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome." International journal of oncology 61(4).
	Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short‑term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross‑resistance and association with progression‑free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment‑naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross‑resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.

Bjorkstrom, L. M., et al. (2021). "The Impact of Preoperative Assessment and Planning on the Outcome of Benign Hysterectomy - A Systematic Review." Geburtshilfe und Frauenheilkunde 81(2): 200-213.
	Knowledge concerning the impact of preoperative planning, patient information and patient factors on the outcome of benign hysterectomy is incomplete. This systematic review summarizes the current knowledge on the effect of preoperative planning and of preoperative patient factors on the outcome of benign hysterectomy. The PubMed/PubMed Central/MEDLINE, Scopus, Web of Science, TRIP Medical Database, Prospero and the Cochrane Library databases were searched. Inclusion criteria were prospective trials, hysterectomy for benign disease, systematic preoperative assessment, and article in English. Eighteen articles were included and categorized according to their main aims: use of a preoperative checklist, preoperative decision-making, preoperative information, and the effect on the outcome of surgery of factors that concerns patients preoperatively. Focused and well directed preoperative assessment and thoroughness in the preoperative decision-making was associated with positive postoperative outcomes. The use of a checklist reduced the overall rate of hysterectomy and increased the use of minimally invasive surgery. Women were often inadequately informed before hysterectomy about the possible side effects after surgery. Preoperative anxiety and preoperative pain were associated with postoperative pain and lower quality of life. The indication for surgery had an impact on the reported quality of life postoperatively. The extent of preoperative planning seemed to affect the outcome of surgery. Preoperative patient factors influenced the postoperative recovery. Prehabilitation measures need further development and should be integrated in the preoperative planning. Prospective studies are warranted to evaluate and improve the preoperative planning in a systematic setting before performing hysterectomy for benign disease.Copyright © 2021 Georg Thieme Verlag. All rights reserved.

Black Kristin, A., et al. (2024). "Incidence of venous thromboembolism in patients with ovarian cancer receiving neoadjuvant chemotherapy: systematic review and meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Objective: Venous thromboembolism is associated with significant patient morbidity, mortality, and can lead to delays in treatment for patients with cancer. The objectives of this study were to identify the incidence of venous thromboembolism in patients with advanced ovarian cancer receiving neoadjuvant chemotherapy, and identify risk factors for venous thromboembolism.; Methods: A systematic literature search of biomedical databases, including Ovid Medline, Web of Science, Scopus, CINAHL, and Embase was performed on December 6, 2022 and updated on December 21, 2023 for peer reviewed articles. Studies were included if they were cohort studies or randomized controlled trials that evaluated the incidence of venous thromboembolism for patients with ovarian cancer receiving neoadjuvant chemotherapy. Risk of bias assessment was performed using the Newcastle Ottawa Scale for cohort studies and the Cochrane risk of bias tool for randomized controlled trials. Random effects meta-analysis was used to pool results across studies.; Results: A total of 2636 studies were screened, and 11 were included in the review. Ten were retrospective cohort studies, and one was a randomized controlled trial. The incidence of venous thromboembolism in the included studies ranged from 0% to 18.9%. The pooled incidence rate of venous thromboembolism was 10% (95% confidence interval (CI) 7% to 13%). This remained significant when restricted to only studies with a low risk of bias (pooled incidence of 11%, 95% CI 9% to 14%). Body mass index of ≥30 kg/m 2 was a significant risk factor for venous thromboembolism with a pooled odds ratio of 1.76 (95% CI 1.13 to 2.76) CONCLUSIONS: The results from this study demonstrated a 10% incidence of venous thromboembolism for patients with advanced ovarian cancer receiving neoadjuvant chemotherapy. This suggests that there may be a role for universal thromboprophylaxis in this population.; Trial Registration: PROSPERO CRD42022339602.; Competing Interests: Competing interests: SP has received consultancy fees from GSK. (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Black Tie, M. and Inc (2022). Ovarian Rejuvenation Using Platelet Rich Plasma (PRP) & Autologous Tissue Stromal Vascular Fraction (tSVF) and Cell Enriched tSVF.
	No Results Available Procedure: lipoaspiration harvest tSVF|Procedure: Platelet Rich Plasma|Procedure: Endovaginal Ultrasound|Device: Cellular Isolation cSVF|Drug: Normal Saline (NS) .9% 10 mL Injection|Device: emulsification tSVF Patient Safety For Procedure|Menstrual Resumption|Hormonal Response|Ovarian Morphology|Bone Density and Body Composition Female Phase 1 100 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment OVARIAN REJUV August 15, 2025

Blackburn, L., et al. (2021). "Effect of Foot Reflexology and Aromatherapy on Anxiety and Pain During Brachytherapy for Cervical Cancer." Oncology Nursing Forum 48(3): 265-276.
	OBJECTIVES: To determine if the addition of aromatherapy and foot reflexology to the standard of care improves pain and anxiety in patients receiving brachytherapy for cervical cancer. SAMPLE & SETTING: 41 women with locally advanced cervical cancer who received intracavitary brachytherapy as part of their treatment. METHODS & VARIABLES: Participants were randomized to either the control group, which received the standard-of-care management during brachytherapy, or the intervention group, which received the addition of aromatherapy and foot reflexology to standard of care. Participants rated their pain on a numeric rating scale and anxiety on the State-Trait Anxiety Inventory (STAI) and a numeric rating scale at five different time points. RESULTS: All average pain and anxiety scores were equal or lower at each key time point for the intervention group. Statistically significant differences were found for the intervention group for anxiety on the numeric rating scale and on the STAI, but only post-reflexology. IMPLICATIONS FOR NURSING: Nurses and other healthcare providers can be trained to provide reflexology during painful, anxiety-producing procedures to increase patient tolerance of these treatments and overall quality of life.

Blackwood, J. and K. Rybicki (2021). "Outcomes of Telehealth-Delivered Physical Activity Programs in Adult Cancer Survivors: A Systematic Review." Rehabilitation Oncology 39(3): 128-136.
	Background and Purpose: Reduced physical activity (PA) is associated with poor prognosis in cancer survivors. Clinicians and researchers have attempted to improve adherence to PA recommendations, essentially bridging the gap between the clinic and the home by incorporating telehealth technologies in patients with chronic diseases. However, various approaches to telehealth may be used and the effectiveness of these interventions in cancer survivors is unknown. The purpose of this systematic review was to describe the type of technology used and outcomes of telehealth-delivered PA programs in adult cancer survivors. Method(s): A systematic review was performed to examine telehealth methods used to deliver PA exercise programs in adult cancer survivors. Databases searched for articles included PubMed/Ovid, MEDLINE/Web of Science, and CINAHL Complete via EBSCO. All articles that met the inclusion criteria were appraised by 2 reviewers independently and discussed against inclusion/exclusion criteria. The Cochrane Risk of Bias Assessment was used to assess study quality. Result(s): The search located 21 articles, and 5 met inclusion criteria. Articles included survivors from breast cancer (n = 3), prostate cancer (n = 1), and mixed sample (n = 1), including breast, cervical, endometrial, lung, leukemia, lymphoma, urinary, melanoma, rectal, oral, ovarian, and prostate cancer survivors. Sample size ranged from 41 to 339 and comprised 81.2% breast cancer survivors. PA interventions were delivered via telehealth by telephone calls (2 studies), smartphone apps (2 studies), and one used a combination of telephone calls and text messaging. Limitation(s): Selection bias is possible. Limited types of telehealth technologies were used. Conclusion(s): Limited evidence exists describing better outcomes of telehealth-delivered PA programs in cancer survivors than by traditional home exercise program instruction, and further study is indicated.Copyright © 2021 Lippincott Williams and Wilkins. All rights reserved.

Blagden Sarah, P. (2022). "Targeting MAPK in recurrent, low-grade serous ovarian cancer." Lancet (London, England) 399(10324): 499-501.
	Competing Interests: SPB reports grants and institutional support for clinical trials from NuCana, Sierra Oncology, Redx Pharma, UCB Pharma, Astex Pharma, Tesaro, and BerGenBio, all unrelated to the area of work commented on here.

Blanc-Durand, F., et al. (2023). "A RAD51 functional assay as a candidate test for homologous recombination deficiency in ovarian cancer." Gynecologic Oncology 171: 106-113.
	Rationale: Homologous recombination deficiency (HRD), defined as BRCA1/2 mutation (BRCAmut) or high genomic instability, is used to identify ovarian cancer (OC) patients most likely to benefit from PARP inhibitors. While these tests are useful, they are imperfect. Another approach is to measure the capacity of tumor cells to form RAD51 foci in the presence of DNA damage using an immunofluorescence assay (IF). We aimed to describe for the first time this assay in OC and correlate it to platinum response and BRCAmut. Method(s): Tumor samples were prospectively collected from the randomized CHIVA trial of neoadjuvant platinum +/- nintedanib. IF for RAD51, GMN and gH2AX was performed on FFPE blocks. Tumors were considered RAD51-low if <=10% of GMN-positive tumor cells had >=5 RAD51 foci. BRCAmut were identified by NGS. Result(s): 155 samples were available. RAD51 assay was contributive for 92% of samples and NGS available for 77%. gH2AX foci confirmed the presence of significant basal DNA damage. 54% of samples were considered HRD by RAD51 and presented higher overall response rates to neoadjuvant platinum (P = 0.04) and longer progression-free survival (P = 0.02). In addition, 67% of BRCAmut were HRD by RAD51. Among BRCAmut, RAD51-high tumors seem to harbor poorer response to chemotherapy (P = 0.02). Conclusion(s): We evaluated a functional assay of HR competency. OC demonstrate high levels of DNA damage, yet 54% fail to form RAD51 foci. These RAD51-low OC tend to be more sensitive to neoadjuvant platinum. The RAD51 assay also identified a subset of RAD51-high BRCAmut tumors with unexpected poor platinum response.Copyright © 2023 Elsevier Inc.

Blauvelt, A., et al. (2023). "Malignancy rates through 5 years of follow-up in patients with moderate-to-severe psoriasis treated with guselkumab: Pooled results from the VOYAGE 1 and VOYAGE 2 trials." Journal of the American Academy of Dermatology 89(2): 274-282.
	Background: Malignancy risk surveillance among patients receiving long-term immunomodulatory psoriasis treatments remains an important safety objective.; Objective: To report malignancy rates in patients with moderate-to-severe psoriasis treated with guselkumab for up to 5 years versus general and psoriasis patient populations.; Methods: Cumulative rates of malignancies/100 patient-years (PY) were evaluated in 1721 guselkumab-treated patients from VOYAGE 1 and 2. Malignancy rates (excluding nonmelanoma skin cancer [NMSC]) were compared with rates in the Psoriasis Longitudinal Assessment and Registry. Standardized incidence ratios comparing malignancy rates (excluding NMSC and cervical cancer in situ) between guselkumab-treated patients and the general US population using Surveillance, Epidemiology, and End Results data were calculated, adjusting for age, sex, and race.; Results: Of 1721 guselkumab-treated patients (>7100 PY), 24 had NMSC (0.34/100PY; basal:squamous cell carcinoma ratio, 2.2:1), and 32 had malignancies excluding NMSC (0.45/100PY). For comparison, the malignancy rate excluding NMSC was 0.68/100PY in the Psoriasis Longitudinal Assessment and Registry. Malignancy rates (excluding NMSC/cervical cancer in situ) in guselkumab-treated patients were consistent with those expected in the general US population (standardized incidence ratio = 0.93).; Limitations: Inherent imprecision in determining malignancy rates.; Conclusions: In patients treated with guselkumab for up to 5 years, malignancy rates were low and generally consistent with rates in general and psoriasis patient populations.; Competing Interests: Conflicts of interest Dr Blauvelt has served as a speaker (received honoraria) for AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, and Sanofi, served as a scientific advisor (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. Dr Lebwohl is an employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc, and is a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas, Dermavant Sciences, Dr Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. Dr Langley has served, and has received compensation in the form of grant funding and/or honoraria, as principal investigator for and is on the scientific advisory board or served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pfizer, SUN Pharma, and UCB. Ms Rowland and Dr Chan are employees of Janssen Scientific Affairs, LLC (a subsidiary of Johnson & Johnson), and own Johnson & Johnson ock/stock options. Dr Yang is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson and owns Johnson & Johnson stock/stock options. Ms Miller, Ms You, and Dr Yu are employees of Janssen Research & Development, LLC (a subsidiary of Johnson & Johnson), and own Johnson & Johnson stock/stock options. Dr Thaçi has received honoraria for participation on advisory boards, as a speaker, and for consultancy from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Sharp & Dohme, Morphosys, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz-Hexal, Sanofi, and UCB, and has received research grants from LEO Pharma and Novartis. Dr Foley has received grant support, and/or served on advisory boards, and/or served as a consultant, and/or has received travel grants, and/or has served as a speaker for or received honoraria from AbbVie, Akaal, Amgen, Arcutis, Argenx, Aslan, AstraZeneca, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Evelo, Galderma, GenesisCare, Genentech, GlaxoSmithKline, Hexima, Janssen, Kymab, Leo Pharma, Lilly, Mayne Pharma, MedImmune, Melaseq/Geneseq, Merck, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi, Sun Pharma, Teva, UCB Pharma, and Valeant. Dr Papp has received clinical research grants from, honoraria from, and/or served as a consultant, scientific advisor, investigator, speaker, and/or medical officer for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Avillion, Bausch Health, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals, Dow Pharma, Eli Lilly, Evelo, Galapagos, Galderma, Genentech, Gilead, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck Sharpe & Dohme, Merck-Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Reistone, Roche, Sandoz, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB Pharma, Valeant, vTv Therapeutics, and Xenocor. (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Blay, J. Y., et al. (2023). "Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSe Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial." The Lancet Oncology 24(8): 892-902.
	Background: Sarcoma is a heterogeneous group of diseases with few treatment options. Immunotherapy has shown little activity in studies including unselected sarcomas, but immune checkpoint blockers have shown activity in specific histotypes. We evaluated the activity of pembrolizumab in rare and ultra-rare sarcomas. Method(s): AcSe Pembrolizumab is an ongoing phase 2, basket, multitumour study investigating the activity of pembrolizumab monotherapy in rare cancers. Here, we report the results obtained in patients with selected histotypes of rare sarcomas (incidence of less than one case per 1 000 000 people per year) recruited at 24 French hospitals. Key inclusion criteria were age 15 years or older, Eastern Cooperative Oncology Group performance status of 0-1, and advanced disease that was untreated and resistant to treatment. Patients were given pembrolizumab 200 mg intravenously on day 1 of every 21-day cycle for a maximum of 24 months. The primary endpoint was objective response rate at week 12 using Response Evaluation Criteria in Solid Tumours version 1.1, assessed by local investigators. The primary endpoint and safety were analysed in the intention-to-treat population. The AcSe Pembrolizumab study is registered with ClinicalTrials.gov, NCT03012620. Finding(s): Between Sept 4, 2017, and Dec 29, 2020, 98 patients were enrolled, of whom 97 received treatment and were included in analyses (median age 51 years [IQR 35-65]; 53 [55%] were male; 44 [45%] were female; no data were collected on race or ethnicity). 34 (35%) patients had chordomas, 14 (14%) had alveolar soft part sarcomas, 12 (12%) had SMARCA4-deficient sarcomas or malignant rhabdoid tumours, eight (8%) had desmoplastic small round cell tumours, six (6%) had epithelioid sarcomas, four (4%) had dendritic cell sarcomas, three (3%) each had clear cell sarcomas, solitary fibrous tumours, and myxoid liposarcomas, and ten (10%) had other ultra-rare histotypes. As of data cutoff (April 11, 2022), median follow-up was 13.1 months (range 0.1-52.8; IQR 4.3-19.7). At week 12, objective response rate was 6.2% (95% CI 2.3-13.0), with no complete responses and six partial responses in the 97 patients. The most common grade 3-4 adverse events were anaemia (eight [8%] of 97), alanine aminotransferase and aspartate aminotransferase increase (six [6%]), and dyspnoea (five [5%]). 86 serious adverse events were reported in 37 patients. Five deaths due to adverse events were reported, none of which were determined to be related to treatment (two due to disease progression, two due to cancer, and one due to unknown cause). Interpretation(s): Our data show the activity and manageable toxicity of pembrolizumab in some rare and ultra-rare sarcoma histotypes, and support the PD-1/PD-L1 pathway as a potential therapeutic target in selected histotypes. The completion of the basket study will provide further evidence regarding the activity and toxicity of pembrolizumab in identified rare types of cancer. Funding(s): The Ligue contre le cancer, INCa, MSD. Translation: For the French translation of the abstract see Supplementary Materials section.Copyright © 2023 Elsevier Ltd

Blay, J. Y., et al. (2023). "Long term activity of vemurafenib in cancers with BRAF mutations: the ACSE basket study for advanced cancers other than BRAF V600 -mutated melanoma." ESMO Open 8(6): 102038.
	Background: BRAF inhibitors are approved in BRAF V600 -mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAF V600 -mutated melanoma and NSCLC.; Patients and Methods: Patients with advanced tumours other than BRAF V600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety.; Results: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAF V600 mutations and 10 with BRAF nonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib.; Conclusion: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers. (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Blomqvist, L., et al. (2023). "Preconceptual thyroid peroxidase antibody positivity in women with recurrent pregnancy losses may contribute to an increased risk for another miscarriage." Clinical Endocrinology 98(2): 259‐269.
	OBJECTIVE: To investigate preconceptual thyroid peroxidase antibody (TPO‐ab) positivity and/or thyroid stimulating hormone (TSH) levels in the upper range of normal as risk factors for recurrent unexplained first‐trimester miscarriage. DESIGN: A post‐hoc study of a randomized trial, in which acetylsalicylic acid did not affect the risk of a new miscarriage. PATIENTS: Women (n = 483) with at least three unexplained recurrent first‐trimester miscarriages investigated at a Swedish secondary referral center. MEASUREMENTS: The levels of TPO‐ab and TSH were determined before pregnancy. The occurrence of a new first‐trimester miscarriage was analyzed by logistic regression with adjustments when applicable, for age, number of previous miscarriages, obesity and the investigated covariates levels of TPO‐ab and TSH. RESULTS: Including all first trimester miscarriages, odds ratio (OR) according to presence of TPO‐ab was 1.60 (95% confidence interval [CI]; 0.99‐2.57), after adjustment 1.54 (95% CI; 0.94‐2.53). Very early (biochemical) pregnancy losses occurred more often in women with than without preconceptual TPO‐ab (6.8% vs. 2.0%), OR 3.51 (95% CI; 1.15‐10.71), after adjustment 2.91 (95% CI; 0.91‐9.29). There was no association between TSH in the upper range of normal and a new miscarriage, adjusted OR 0.76 (95% CI; 0.32‐1.83). A prediction model for a new miscarriage included number of previous miscarriages, woman's age and presence of TPO‐ab. CONCLUSION: In women with at least three recurrent unexplained pregnancy losses, the presence of TPO‐ab may contribute to an increased risk of a first‐trimester miscarriage, possibly more pronounced in very early pregnancy. TSH levels 2.5‐4.0 mU/L do not seem to increase the miscarriage risk.

Blomqvist Lennart, R. F., et al. (2022). "Arachidonic acid-induced platelet aggregation and acetylsalicylic acid treatment during pregnancy in women with recurrent miscarriage, a post hoc study." Platelets 33(2): 278-284.
	In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were-0.7 (95%CI; -7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; -4.6; 12.2) U during the late first trimester and 1.7 (95%CI; -6.7; 10.3) U and 4.1 (95%CI; -3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median -84.0% (Q1; Q3; -89.8; -76.3), -79.9% (-84.7; -69.2) and -75.7% (-83.5; -49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester ( p < .0001). There were two (1.9%) complete non-responders to ASA and 32.1% with a partial response. The rate of subsequent miscarriage was not affected by ASA, which did not seem to influence the rate of early miscarriage if treatment was initiated when a viable pregnancy was detectable by ultrasound.

Bø, K. (2024). "Is there evidence for pelvic floor muscle relaxation training in nonneurogenic female bladder outlet obstruction?-A narrative review." Neurourology and Urodynamics.
	INTRODUCTION: Functional bladder outlet obstruction (BOO) in women is postulated to be caused by pelvic floor muscle (PFM) dyssynergia or increased tone. The aim of the present review was to investigate the effect of PFM relaxation training on PFM tone and female BOO symptoms. MATERIALS AND METHODS: This was a narrative review using an open search strategy on PubMed with the search terms "Bladder outlet obstruction" AND "female" AND ("pelvic floor muscles" OR "Kegel"). The risk of bias of the randomized controlled trials (RCTs) was scored with the Physiotherapy Evidence Database (PEDro) scale (0-10). RESULTS: Only three RCTs were found. All three RCTs compared different types of exercise, and no trial compared relaxation training with no or sham treatment. None of the trials reported the effect between groups on the reduction of PFM tone. There was a tendency toward positive effect of PFM relaxation training to improve BOO symptoms in women. PEDro score varied between 4 and 7. Few studies yielded information on the immediate effect of any type of PFM relaxation technique on PFM tone. CONCLUSION: Few RCTs have been conducted on the effect of PFM relaxation training on PFM tone and functional female BOO symptoms. There is an urgent need for RCTs with high methodological and interventional quality in addition to basic research on mechanisms of different relaxation techniques on PFM activity.

Bø, K., et al. (2022). "International urogynecology consultation chapter 3 committee 2; conservative treatment of patient with pelvic organ prolapse: Pelvic floor muscle training." International Urogynecology Journal 33(10): 2633-2667.
	Introduction and Hypothesis: This manuscript from Chapter 3 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) describes the current evidence and suggests future directions for research on the effect of pelvic floor muscle training (PFMT) in prevention and treatment of POP.; Methods: An international group of four physical therapists, four urogynecologists and one midwife/basic science researcher performed a search of the literature using pre-specified search terms on randomized controlled trials (RCTs) in Ovid Medline, EMBASE, CINAHL, Cochrane, PEDro and Scopus databases for publications between 1996 and 2021. Full publications or expanded abstracts in English or in other languages with abstracts in English were included. The PEDro rating scale (0-10) was used to evaluate study quality. Included RCTs were reviewed to summarize the evidence in six key sections: (1) evidence for PFMT in prevention of POP in the general female population; (2) evidence for early intervention of PFMT in the peripartum period for prevention and treatment of POP; (3) evidence for PFMT in treatment of POP in the general female population; (4) evidence for perioperative PFMT; (5) evidence for PFMT on associated conditions in women with POP; (6) evidence for the long-term effect of PFMT on POP. Full publications in English or in other languages with abstracts in English and expanded abstracts presented at international condition specific societies were included. Internal validity was examined by the PEDro rating scale (0-10).; Results: After exclusion of duplicates and irrelevant trials, we classified and included 2 preventive trials, 4 trials in the post-partum period, 11 treatment trials of PFMT for POP in the general female population in comparison with no treatment or lifestyle interventions, 10 on PFMT as an adjunct treatment to POP surgery and 9 long-term treatment trials. Only three treatment studies compared PFMT with the use of a pessary. The RCTs scored between 4 and 8 on the PEDro scale. No primary prevention studies were found, and there is sparse and inconsistent evidence for early intervention in the postpartum period. There is good evidence/recommendations from 11 RCTs that PFMT is effective in reducing POP symptoms and/or improving POP stage (by one stage) in women with POP-Q stage I, II and III in the general female population, but no evidence from 9/10 RCTs that adding PFMT pre- and post -surgery for POP is effective. There are few long-term follow-up studies, and results are inconsistent. There are no serious adverse effects or complications reported related to PFMT.; Conclusions: There are few studies on prevention and in the postpartum period, and the effect is inconclusive. There is high-level evidence from 11 RCTs to recommend PFMT as first-line treatment for POP in the general female population. PFMT pre- and post-POP surgery does not seem to have any additional effect on POP. PFMT is effective and safe but needs thorough instruction and supervision to be effective. (© 2022. The Author(s).)

Bø, K., et al. (2023). "Can you breathe yourself to a better pelvic floor? A systematic review." Neurourology and Urodynamics 42(6): 1261-1279.
	Introduction: Some authors suggest that breathing exercises should be recommended instead of or in combination with pelvic floor muscle training (PFMT) to prevent and treat urinary incontinence (UI) and pelvic organ prolapse (POP).; Aims: The primary aim of the present study was to investigate the evidence for breathing as an intervention alone or in addition to PFM contraction in treatment of UI and POP.; Materials & Methods: This systematic review included short-term experimental studies and randomize controlled trials (RCTs) indexed on PubMed, EMBASE, and PEDro database. A form was used to extract data that was analyzed qualitatively due to the heterogeneity in interventions and outcome measures of the included studies. The individual methodological quality of RCTs was analyzed using the PEDro scale.; Results: A total of 18 studies were included, 374 participants from short-term experimental studies and 765 from nine RCTs. PEDro score varied from 4 to 8. Activation of the PFM during expiration was significantly less than during a PFM contraction. In general, the RCTs showed that training the PFM is significantly more effective to improve PFM variables and UI and POP than breathing exercises, and that adding breathing exercises to PFMT have no additional effect.; Conclusion: This systematic review indicates that the evidence for incorporating breathing exercise in clinical practice in addition to or instead of PFMT is scant or non-existing, both based on short-term experimental studies and small RCTs. (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Bobisse, S., et al. (2023). "A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer." Nature Cancer 4(10): 1410-1417.
	We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study (NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.Copyright © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

Boccasanta, P., et al. (2021). "A Minimally Invasive Technique for the 1-Stage Treatment of Complex Pelvic Floor Diseases: Laparoscopic-Pelvic Organ Prolapse Suspension." Female Pelvic Medicine & Reconstructive Surgery 27(1): 28-33.
	OBJECTIVE: The aim of this prospective study was to assess the safety and effectiveness of a new single laparoscopic operation devised to relieve obstructed defecation, gynecologic and urinary symptoms in a large series of female patients with multiorgan pelvic prolapse. METHODS: We submitted 384 female patients to laparoscopic pelvic organ prolapse suspension operation, a new technique based on suspension of the middle pelvic compartment, by using a polypropylene mesh and followed up 368 of them, with defecography performed 12 months after surgery and a standardized protocol. RESULTS: The 368 patients were followed-up for 36.3 (±4.4) months, Recurrence rate was 4.9% for obstructed defecation syndrome and 3.3% for stress urinary incontinence. Complication rate was 2.9%. The mean period of daily activity resumption was 16.3 days (±4.8 days). Anorectal and urogynecologic symptoms and scores significantly improved after the operation (P < 0.001), with no worsening of anal continence. Incidence of postoperative fecal urgency was 0%. Postoperative defecography showed a significant (P < 0.001) improvement of all parameters in 315 patients (82%). Short Form 36 Health Survey score significantly improved after the operation (P < 0.01). An excellent/good overall Satisfaction Index was reported by 78.0% of patients. CONCLUSIONS: In our experience the Laparoscopic-Pelvic Organ Prolapse Suspension seems to be safe and effective as a 1-stage treatment of associated pelvic floor diseases. Randomized studies with an appropriate control group and longer follow-up are now needed to assess the effectiveness of this promising technique.

Bochum Ruhr University, o. (2021). Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia.
	No Results Available Procedure: LLETZ|Procedure: LEEP Surgical specimen margin status|Intraoperative and postoperative complication rate|Cone size|Patient's pain|HPV clearance|Cone volume Female Not Applicable 206 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment LLETZ-2 January 2024

Bochum Ruhr University, o. (2022). Large Loop Excision of the Transformation Zone (LLETZ) With vs Without IntraOperative Application of Lugol's Iodine.
	Aim of the study The aim of this study is to answer the question under prospective randomized conditions whether LLETZ performed with the aid of iodine assay with selection of the resection line in the iodine-positive region leads to a lower rate of R1 resections compared with standard LLETZ without iodine assay. Primary Purpose : Treatment Allocation : Randomized Interventional Model : Parallel Assignment Interventional Model Description: Prospective randomized trial with 2 groups (use vs not use of Lugol's iodine during LLETZ) Masking : Single (Participant) Masking Description: Participants are not aware of their treatment allocation in order not to influence patient reported outcomes

Bockorny, B., et al. (2023). "Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) in patients with recurrent platinum refractory/resistant ovarian cancer (041)."  176: S35‐S36.
	Objectives: Botensilimab (BOT) promotes optimized T‐cell priming, activation, and memory formation by strengthening antigen‐presenting cell/T‐cell co‐engagement. As a fragment crystallizable (Fc)‐enhanced next‐generation anticytotoxic T‐lymphocyte antigen 4 (CTLA‐4) antibody, BOT also promotes intratumoral Treg depletion to improve potency while mitigating difficult‐to‐treat side effects associated with first‐generation CTLA‐4 therapy. Results from an expanded phase IA/B study (NCT03860272) in patients with recurrent platinum‐resistant/refractory ovarian cancer treated with BOT plus balstilimab (BAL; anti‐programmed cell death protein 1 [PD‐1]) are presented. Methods: Patients received BOT 1 or 2 mg/kg q6w + BAL 3 mg/kg every 2 weeks. Crossover to combination treatment from BOT monotherapy (rescue) is permitted. Endpoints include incidence of adverse events (AE), objective response rate (ORR; unconfirmed responses included), disease control rate (DCR; the best overall response of either stable disease [SD] or a complete [CR] or partial response [PR]), duration of response (DOR), progression‐free survival (PFS), and overall survival (OS). Enrollment is ongoing. Results: Seventeen patients were evaluated for safety and efficacy (treated as of April 7, 2022, with ≥1 q6w tumor imaging assessment), including one rescue patient; data cutoff August 10, 2022. Patients were heavily pretreated, and the median number of prior lines of therapy was 4 (range: 2–7). The most common histology type was high‐grade serous. The median duration of study treatment was 3.2 months (range: 0.9–19.6), with a median follow‐up of 8.8 months (range: 2.0–29.2). ORR measured 29% (5/17; 95% CI: 13–53; 4 confirmed PRs, 1 unconfirmed CR) (Graph). One patient has an ongoing PR at 24 weeks (−100% reduction of target lesions with residual non‐targets), another patient with an unconfirmed CR at 18 weeks developed a solitary new lesion which was radiated and now has no evidence of disease at 90+ weeks, and the rescue patient had prolonged SD on BOT monotherapy for 66 weeks followed by a PR once BAL was added. The safety profile in all 17 patients continues to be favorable, with no cases of hypophysitis, myocarditis, or pneumonitis of any grade. Grade 1/2, 3, or 4 treatment‐related adverse events (TRAEs) occurred in 94%, 24%, and 6% of patients, respectively, with no grade 5 TRAEs reported. The only grade 3 or 4 TRAE occurring in more than one patient was diarrhea or colitis (18%). Further evaluation of biomarkers is ongoing, including paired biopsies (before/during treatment). Conclusions: BOT plus BAL demonstrates meaningful activity in heavily pretreated patients with recurrent platinum‐resistant/refractory ovarian cancer who are historically unresponsive to immunotherapy. Randomized studies are planned. [Formula presented]

Bodepudi, R., et al. (2023). "Myoinositol Versus Metformin in the Treatment of Polycystic Ovarian Syndrome: A Systematic Review." Cureus 15(7): e41748.
	Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice in the treatment of PCOS is a direct consequence of the lack of sufficient evidence on alternative treatment strategies, as well as a poor understanding of the disorder itself. The aim of our systematic review was to assess the therapeutic advantages and adverse effects of metformin (MET), a standard treatment modality, with myoinositol (MI), a recent substitute that may be used alone or in combination with other remedies to treat PCOS. A literature search was done using PubMed Central, PubMed, Medline, Cochrane, Science Direct, and Google Scholar. Studies were limited to those published in English between 2012 and 2022 that focused on the management of PCOS with both MET and MI. The systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Using standard quality assessment tools, two reviewers independently assessed the content of the incorporated studies. Three meta-analyses, eight randomized controlled trials (RCTs), and one non-randomized non-controlled trial (NN-RCT) were deemed eligible. Following extensive analysis, we found that MET and MI are comparable in their effects on clinical, hormonal, and biochemical profiles. MI, however, had a better safety profile and tolerance due to minimal side effects compared to MET. These results demonstrate the potential role of MI as a novel asset in the armamentarium in the management of PCOS.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Bodepudi et al.)

Boedt, T., et al. (2023). "A blended preconception lifestyle programme for couples undergoing IVF: lessons learned from a multicentre randomized controlled trial." Human Reproduction Open 2023(4).
	STUDY QUESTION: What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition? SUMMARY ANSWER: This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid‐19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes. WHAT IS KNOWN ALREADY: Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF. STUDY DESIGN, SIZE, DURATION: A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid‐19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy). PARTICIPANTS/MATERIALS, SETTING, METHODS: Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)‐programme in addition to standard care. The PreLiFe‐programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was 'time to ongoing pregnancy'. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness). LIMITATIONS, REASONS FOR CAUTION: The findings of this RCT should be considered exploratory, as the Covid‐19 pandemic limited its power and the actual use of the mobile application was low. WIDER IMPLICATIONS OF THE FINDINGS: This is the first multicentre RCT evaluating the effect of a blended preconception lifestyle programme for women and their partners undergoing IVF on both reproductive and lifestyle outcomes. This exploratory RCT highlights the need for further studies into optimal intervention characteristics and actual use of preconception lifestyle programmes, as well as RCTs evaluating effectiveness. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Research foundation Flanders (Belgium) (FWO‐TBM; reference: T005417N). No competing interests to declare.

Boedt, T., et al. (2022). "Evaluation of a stand-alone mobile mindfulness app in people experiencing infertility: the protocol for an exploratory randomised controlled trial (MoMiFer-RCT)." BMJ Open 12(2): e050088.
	INTRODUCTION: Infertility and its treatment bring a considerable emotional burden. Increasing evidence demonstrates the effectiveness of smartphone-delivered mindfulness apps for reducing symptoms of emotional distress in both clinical and non-clinical populations. Evidence on this topic in women, men and couples experiencing infertility is currently under-represented. The aim of the MoMiFer study is, therefore, to investigate the efficacy of a stand-alone mobile mindfulness app on symptoms of emotional distress and fertility-related quality of life in people experiencing infertility. METHODS AND ANALYSIS: This study is an exploratory randomised controlled trial (RCT) with open enrollment. The primary outcomes are symptoms of emotional distress and fertility-related quality of life. Secondary outcomes are mindfulness skills, repetitive negative thinking, self-compassion, user-rated quality of the stand-alone mobile mindfulness app and use of the app. Experience sampling method and standardised self-report questionnaires are combined within a repeated measures design to measure the effects of the stand-alone mobile mindfulness app on the primary and secondary outcomes, apart from the use of the app. The latter will be evaluated through app tracking. People, including women, men and couples, experiencing infertility (n=60) will be randomised to an intervention group receiving the stand-alone mobile mindfulness app for 3 months or a wait-list control group. The app follows the format and content of Mindfulness-Based Stress Reduction. Data will be collected at baseline, at 1.5 months and 3 months after randomisation. Analysis will be according to intention to treat and based on general linear modelling and multilevel mixed-effects modelling. ETHICS AND DISSEMINATION: This study received approval from the Medical Ethical Committee of the Leuven University Hospital (Belgium). The findings of this exploratory RCT will be disseminated through presentations at public lectures, scientific institutions and meetings, and through peer-reviewed scientific articles. TRIAL REGISTRATION NUMBER: NCT04143828.

Boeira Jéssica Tamara, R., et al. (2022). "Pelvic floor physiotherapy's role in public health for pregnant women: an integrative review." Fisioter. Bras 22(6): 912-930.
	
Boelig, R. C., et al. (2022). "Vaginal progesterone vs intramuscular 17-hydroxyprogesterone caproate for prevention of recurrent preterm birth: a randomized controlled trial." American Journal of Obstetrics and Gynecology 226(5): 722.e721‐722.e712.
	BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality, and previous preterm birth is one of the strongest risk factors for preterm birth. National and international obstetrical societies have different recommendations regarding progesterone formulation for the prevention of recurrent preterm birth. OBJECTIVE: This study aimed to determine whether vaginal progesterone is superior to 17‐hydroxyprogesterone caproate in the prevention of recurrent preterm birth in patients with singleton pregnancies who had a previous spontaneous preterm birth. STUDY DESIGN: This was an open‐label multicenter pragmatic randomized controlled trial at 5 US centers of patients with singleton pregnancies at <24 weeks of gestation who had a previous spontaneous preterm birth randomized 1:1 to either 200 mg vaginal progesterone suppository nightly or 250 mg intramuscular 17‐hydroxyprogesterone caproate weekly from 16 to 36 weeks of gestation. Based on the estimated recurrent preterm birth rate of 36% with 17‐hydroxyprogesterone caproate, 95 participants were needed in each arm to detect a 50% reduction in preterm birth rate with vaginal progesterone, with 80% power and 2‐sided alpha of 0.05. The primary outcome was preterm birth at <37 weeks of gestation. Prespecified secondary outcomes included preterm birth at <34 and <28 weeks of gestation, mean gestational age at delivery, neonatal morbidity and mortality, and measures of adherence. Analysis was by intention to treat. The chi‐square test and Student t test were used as appropriate. P<.05 was considered significant. RESULTS: Overall, 205 participants were randomized; 94 participants in the vaginal progesterone group and 94 participants in 17‐hydroxyprogesterone caproate group were included. Although gestational age at enrollment was similar, those assigned to vaginal progesterone initiated therapy earlier (16.9±1.4 vs 17.8±2.5 weeks; P=.001). Overall continuation of assigned formulation until delivery was similar (73% vs 69%; P=.61). There was no significant difference in preterm birth at <37 (31% vs 38%; P=.28; relative risk, 0.81 [95% confidence interval, 0.54‐1.20]), <34 (9.6% vs 14.9%; P=.26; relative risk, 0.64 [95% confidence interval, 0.29‐1.41]), or <28 (1.1% vs 4.3%; P=.37; relative risk, 0.25 [95% confidence interval, 0.03‐2.20]) weeks of gestation. Participants in the vaginal progesterone group had a later mean gestational age at delivery than participants in the 17‐hydroxyprogesterone caproate group (37.36±2.72 vs 36.34±4.10 weeks; mean difference, 1.02 [95% confidence interval, 0.01‐2.01]; P=.047). CONCLUSION: Vaginal progesterone did not reduce the risk of recurrent preterm birth by 50% compared with 17‐OHPC; however, vaginal progesterone may lead to increased latency to delivery. This trial was underpowered to detect a smaller, but still clinically significant, difference in the efficacy of preterm birth prevention. Patient factors that impact adherence and ability to obtain medication in a timely fashion should be included in counseling on progesterone selection.

Boelig Rupsa, C. (2023). "Obstetric Indications for Progestin Therapy." Obstetrics and gynecology clinics of North America 50(1): 101-107.
	Specifically, meta-analyses of randomized trials demonstrate that vaginal progesterone reduces the risk of preterm birth in selected high-risk singleton pregnancies. 17-OHPC may also reduce the risk of recurrent preterm birth in singletons. Finally, one trial suggests that vaginal progesterone may also be beneficial in improving live birth rates in singletons with prior miscarriages and early pregnancy bleeding.; Competing Interests: Conflicts of interest No conflicts of interest, financial or otherwise, to disclose. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Boere, I., et al. (2023). "CINOVA: a phase II study of CPC634 (nanoparticulate docetaxel) in patients with platinum resistant recurrent ovarian cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(8): 1247-1252.
	Objective: Recurrent platinum-resistant ovarian cancer has a poor prognosis with limited therapeutic options. Sub-therapeutic intra-tumoral drug concentrations may add to therapy resistance. CPC634 (docetaxel entrapped in CriPec nanoparticles) was designed to enhance tumor accumulation of drug with localized drug release at the target site to increase therapeutic efficacy. This study investigated the therapeutic effect of CPC634 in patients with platinum-resistant ovarian cancer.; Methods: According to a Simon 2-stage design trial, the first stage included 13 patients, and 12 patients were enrolled in the second stage. Eligible patients had measurable disease and had progressed ≤6 months after the last platinum-based therapy. Platinum-refractory disease was excluded. In stage 1, the number of previous treatment lines was unlimited; in the second stage, a maximum of two prior lines altogether were allowed. The primary endpoint was the objective response rate by Response Evaluation Criteria in Solid Tumor (RECIST) V1.1. Secondary endpoints included safety, progression-free survival at 6 months, cancer antigen 125 (CA125) response, and disease control rate.; Results: The patients' median age was 66 years (range 22-77) and most were International Federation of Gynecology and Obstetrics (FIGO) stage III (56%). The median number of previous treatment lines was 3 (range 3-5) in stage I and 2 (range 1-4) in stage II of the study. None of the patients had an objective response, one patient had a CA125 response (5%), and seven patients had stable disease at first evaluation (35%). Median progression-free survival was 1.4 months in stage 1 and 3.0 months in stage 2. Adverse events (all grades) were mainly gastrointestinal in 24 patients (96%), fatigue in 11 (44%), dyspnea in 10 (40%), and infections in 10 (40%) of patients. Grade 3 or higher adverse events occurred in 14 patients (36%), including gastrointestinal in 4 (16%), anemia in 3 (12%), and febrile neutropenia, fatigue, chronic kidney disease, dehydration, and hypertension each in 1 (4%) patient. The trial was stopped prematurely due to futility.; Conclusions: Treatment with CPC634 was feasible, but without apparent clinical activity in patients with recurrent platinum-resistant ovarian cancer. Side effects were mainly gastrointestinal in 24 (96%) patients, including nausea, vomiting, and decreased appetite, fatigue, anemia, and dyspnea.; Competing Interests: Competing interests: CJFR was employee and is meanwhile paid consultant for Cristal Therapeutics, while RH was employed till August 2021 by Cristal Therapeutics. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Boero, V., et al. (2023). "Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up." Journal of Lower Genital Tract Disease 27(4): 365-372.
	Objective: The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery.; Methods: Eligible for this study were women aged 18-85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors' center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires.; Results: Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia ( p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms ( p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids ( p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients.; Conclusions: Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.; Competing Interests: The authors have declared they have no conflicts of interest. (Copyright © 2023, ASCCP.)

Boersen, Z., et al. (2021). "Determining the effectiveness of cognitive behavioural therapy in improving quality of life in patients undergoing endometriosis surgery: a study protocol for a randomised controlled trial." BMJ Open 11(12): e054896.
	Introduction: Endometriosis can cause chronic pain and subfertility thereby negatively affecting quality of life (QoL). Surgical removal of endometriosis lesions leads to improved health-related QoL, although not to the level of QoL of healthy controls. Pain intensity and cognitions regarding pain can play a crucial role in this health-related QoL following surgical treatment. Cognitive behavioural therapy (CBT) is a psychological treatment. In patients with chronic pain caused by a variety of medical conditions, CBT is effective in improving QoL. We designed a research protocol to investigate the effect of CBT on QoL in patients with endometriosis-associated chronic pain who are undergoing surgery.; Methods and Analysis: This is a study protocol for a randomised controlled trial in which 100 patients, undergoing endometriosis removal surgery due to endometriosis-associated chronic pain, will be randomised between post-surgery usual care with CBT and post-surgery usual care only. Participants in the CBT group will additionally receive seven sessions of CBT, focused on expectancy management, cognitions regarding pain and emotional and behavioural impact of pain. To determine the primary outcome Quality of life, both groups will complete questionnaires assessing QoL. The secondary outcomes pain intensity, pain cognitions, fatigue and perceived stress are also measured using questionnaires. Additionally, a marker for stress (cortisol extracted from a hair sample) will be assessed at T0 (baseline assessment), T1 (post-intervention; 2 weeks after completion of all CBT sessions) and T2 (follow-up; 14 weeks after T1). Statistical analysis will be performed using SPSS software.; Ethics and Dissemination: The study protocol has been approved by the Medical Ethical Committee of the region Arnhem-Nijmegen from the Radboud University Medical Centre on 2 September 2020. The findings of this study will be published in scientific journals and will be presented at scientific conferences.; Trial Registration Number: NCT04448366.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bofill, R., et al. (2020). "Interventions commonly available during pandemics for heavy menstrual bleeding: an overview of Cochrane Reviews." The Cochrane Database of Systematic Reviews 7: CD013651.
	Background: Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers.; Objectives: To summarise the evidence from Cochrane Reviews evaluating interventions for heavy menstrual bleeding that are commonly available during pandemics.; Methods: We sought published Cochrane Reviews, evaluating interventions that can continue during pandemics for women with heavy menstrual bleeding with no known underlying cause. We identified Cochrane Reviews by searching the Cochrane Database of Systematic Reviews in June 2020. The primary outcome was menstrual bleeding. Secondary outcomes included quality of life, patient satisfaction, side effects, and serious adverse events. We undertook the selection of systematic reviews, data extraction, and quality assessment in duplicate. We resolved any disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool, and the certainty of the evidence for each outcome using GRADE methods.; Main Results: We included four Cochrane Reviews, with 11 comparisons, data from 44 randomised controlled trials (RCTs), and 3196 women. We assessed all the reviews to be high quality. Non-steroidal anti-inflammatory drugs (NSAIDs) NSAIDs may be more effective in reducing heavy menstrual bleeding than placebo (mean difference (MD) -124 mL per cycle, 95% confidence interval (CI) -186 to -62 mL per cycle; 1 RCT, 11 women; low-certainty evidence). Mefenamic acid may be similar to naproxen (MD 21 mL per cycle, 95% CI -6 to 48 mL per cycle; 2 RCTs, 61 women; low-certainty evidence), and NSAIDs may be similar to combined hormonal contraceptives for heavy menstrual bleeding (MD 25 mL per cycle, 95% CI -22 to 73 mL per cycle; 1 RCT, 26 women; low-certainty evidence). NSAIDs may be be less effective in reducing menstrual bleeding than antifibrinolytics (relative risk (RR) 0.70, 95% CI 0.58 to 0.85; 2 RCTs, 161 women; low-certainty evidence). We are uncertain whether NSAIDs reduce menstrual blood loss more than short-cycle progestogens (RR 0.80, 95% CI 0.49 to 1.32; 1 RCT 32 women; very low-certainty evidence). Antifibrinolytics Antifibrinolytics appear to be more effective in reducing heavy menstrual bleeding than placebo (MD -53 mL per cycle, 95% CI -63 to -44 mL per cycle; 4 RCTs, 565 women; moderate-certainty evidence). Antifibrinolytics may be similar to placebo on the incidence of side effects (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, 297 women; low-certainty evidence), and they are probably similar on the incidence of serious adverse events (thrombotic events; RR 0.10, 95% CI 0.00 to 2.46; 2 RCT, 468 women; moderate-certainty evidence). Antifibrinolytics may be more effective in reducing heavy menstrual bleeding than short-cycle progestogen (MD -111 mL per cycle, 95% CI -178 mL to -44 mL per cycle; 1 RCT, 46 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to short-cycle progestogens on quality of life (RR 1.67, 95% CI 0.76 to 3.64; 1 RCT, 44 women; very low-certainty evidence), patient satisfaction (RR 0.91, 95% CI 0.59 to 1.39; 1 RCT, 42 women; very low-certainty evidence), or side effects (RR 0.85, 95% CI 0.65 to 1.12; 3 RCTs, 211 women; very low-certainty evidence). We are uncertain whether antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with long-cycle progestogen (MD -9 points per cycle, 95% CI -30 to 12 points per cycle; 2 RCTs, 184 women; low-certainty evidence). Antifibrinolytics may increase self-reported improvement in menstrual bleeding when compared with long-cycle medroxyprogesterone acetate (RR 1.32, 95% CI 1.08 to 1.61; 1 RCT, 94 women; low-certainty evidence). Antifibrinolytics may be similar to long-cycle progestogens on quality of life (MD 5, 95% CI -2.49 to 12.49; 1 RCT, 90 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to long-cycle progestogens on side effects (RR 0.58, 95% CI 0.33 to 1.00; 2 RCTs, 184 women; very low-certainty evidenc ). There were no trials comparing antifibrinolytics to combined hormonal contraceptives. Combined hormonal contraceptives Combined hormonal contraceptives appear to be more effective for heavy menstrual bleeding than placebo or no treatment (RR 13.25, 95% CI 2.94 to 59.64; 2 RCTs, 363 women; moderate-certainty evidence). Combined hormonal contraceptives are probably similar to placebo on the incidence of side effects (RR 1.53, 95% CI 0.90 to 2.60; 2 RCTs, 411 women; moderate-certainty evidence). Progestogens There were no trials comparing progestogens to placebo. Limitations in the evidence included risk of bias in the primary RCTs, inconsistency between the primary RCTs, and imprecision in effect estimates.; Authors' Conclusions: There is moderate-certainty evidence that antifibrinolytics and combined hormonal contraceptives reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that NSAIDs reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short-cycle progestogens, but we are unable to draw conclusions about the effects of antifibrinolytics compared to long-cycle progestogens, on low-certainty evidence. (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Bogani, G., et al. (2022). "Radiomics and Molecular Classification in Endometrial Cancer (The ROME Study): A Step Forward to a Simplified Precision Medicine." Healthcare (Basel, Switzerland) 10(12).
	Molecular/genomic profiling is the most accurate method to assess prognosis of endometrial cancer patients. Radiomic profiling allows for the extraction of mineable high-dimensional data from clinical radiological images, thus providing noteworthy information regarding tumor tissues. Interestingly, the adoption of radiomics shows important results for screening, diagnosis and prognosis, across various radiological systems and oncologic specialties. The central hypothesis of the prospective trial is that combining radiomic features with molecular features might allow for the identification of various classes of risks for endometrial cancer, e.g., predicting unfavorable molecular/genomic profiling. The rationale for the proposed research is that once validated, radiomics applied to ultrasonographic images would be an effective, innovative and inexpensive method for tailoring operative and postoperative treatment modalities in endometrial cancer. Patients with newly diagnosed endometrial cancer will have ultrasonographic evaluation and radiomic analysis of the ultrasonographic images. We will correlate radiomic features with molecular/genomic profiling to classify prognosis.

Bogani, G., et al. (2023). "Tisotumab vedotin in recurrent or metastatic cervical cancer." Current problems in cancer 47(3): 100952.
	Tisotumab vedotin (TV) is an antibody-drug conjugate used for the treatment of adult patients with recurrent or metastatic cervical cancer. TV comprised of a monoclonal antibody against tissue factor and monomethyl auristatin E (MMAE), a potent inhibitor of cell division. The innovaTV-201 and innovaTV-204/GO30xx/ENGOT-cx6 trials showed that TV has clinically meaningful and durable antitumor activity in pretreated patients with recurrent or metastatic cervical cancer. The innovaTV-204 trial showed that TV monotherapy resulted in an objective response rate of 24% (including 7% and 17% complete and partial responses, respectively). In September 2021, the US Food and Drugs Administration (FDA) granted accelerated approval to TV for the treatment of recurrent or metastatic cervical cancer patients with disease progression on or after chemotherapy. The ongoing randomized, open-label Phase 3 innovaTV-301/ENGOTcx12/GOG-30xx trial will assess the effect of TV in pre-treated recurrent or metastatic cervical cancer. Meanwhile, the phase 1b/2 trial ENGOT Cx8/GOG 3024/innovaTV-205 is testing other possible combination between TV and other treatments. TV is characterized by a promising antitumor activity and an acceptable safety profile. Moreover, the preliminary data highlighted the feasibility of using TV in first line. In the first line, TV in combination with carboplatin or pembrolizumab provides an ORR of 55% and 41%, respectively Although the effect of adding TV to the current standard of care in first-line (carboplatin plus pembrolizumab) is still under evaluation, we expected to observe impressive results in the cervical cancer population. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bogani, G., et al. (2023). "Mirvetuximab soravtansine-gynx: first antibody/antigen-drug conjugate (ADC) in advanced or recurrent ovarian cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Mirvetuximab soravtansine-gynx (MIRV) is a conjugate of a folate receptor alpha (FRα)-directed antibody and the maytansinoid microtubule inhibitor, DM4. Accumulating pre-clinical and clinical data supported the safety and anti-tumor activity of MIRV in tumors expressing FRα. In 2017, a phase I expansion study reported the first experience of MIRV in FRα-positive platinum-resistant ovarian cancer with promising results. However, the phase III FORWARD I study failed to demonstrate a significant benefit of MIRV in FRα-positive tumors. On the basis of the data reported from this latter study, MIRV was then explored in the FRα-high population only and using a different folate receptor assay. The phase II SORAYA trial supported the adoption of MIRV in this setting. Hence, the US Food and Drug Administration granted accelerated approval of MIRV for patients with FRα-positive platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens. Moreover, the results of the MIRASOL trial showed a significant reduction in the risk of tumor progression or death among patients treated with MIRV versus chemotherapy. VENTANA FOLR1 (FOLR-2.1) was approved as a companion diagnostic test to identify FRα patients. MIRV appears to be a significant asset in managing advanced or recurrent ovarian cancer. Further trials are needed to confirm these promising results, even in the neoadjuvant, adjuvant, and maintenance settings.; Competing Interests: Competing interests: GB: Consulting/advisory role with Novartis. RLC: Consulting/advisory role: Merck, Genentech/Roche, Paravance, AstraZeneca, Novartis, Genmab, GSK, Gilead, Daiichi-Sankyo, Easai, OncXerna, Immunogen, Mersana, Novocure, Verastem, AbbVie; research funding: AstraZeneca, Clovis, Merck, Roche/Genentech, Abbott/AbbVie, Karyopharm. IV: Consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis. IRC: Consulting fees from Agenus, Amgen, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, F Hoffmann-La Roche, Genmab, GSK, Immunogen, Mersana, MSD, Novocure, Novartis, Netrispharma, OncXerna, Sanofi, Transgene, Seagen, Adaptimmune, Verastem Oncology. AO: Consulting/Advisory role: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, ImmunoGen, Genmab, Mersana, GSK, Deciphera, AGENUS, Corcept Therapeutics, Eisai, EMD Serono, Medison, Merck Sharp & Dohme, Novocure, prIME Oncology, Shattuck Labs, Sutro Biopharma, ITeos Therapeutics, Amgen; research funding: AbbVie, Abililty Pharmaceuticals, Advaxis, Aeterna Zentaris, Aprea Therapeutics, Clovis Oncology, Eisai, Roche, Regeneron, Agenus, AstraZeneca, BeiGene, Belgian Gynaecological Oncology Group (BGOG), Bristol Myers Squibb International Corporation (BMS), Corcept Therapeutics, ImmunoGen, Iovance Biotherapeutics, Lilly, Medimmune, Merck, Merck Sharp & Dohme, Mundipharma Research, Novartis FarmacÃutica, Seagen, Seattle Genetics, Sutro Biopharma, Tesaro, Verastem (all payments institutional); travel, accommodations, expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche. DOM: Consult and/or Advisory Boards: AbbVie, AdaptImmune, Agenus, Arquer Diagnostics, AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Bio, Eisai, Elevar, Exelixis, Genentech, Genelux, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche, ImmunoGen, Imvax, InterVenn, INXMED, IOVANCE Biotherapeutics, Janssen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics, Luzsana Biotechology, Merck & Co, Merck Sharp & Dohme Corp, Mersana Therapeutics, Myriad, Novartis, NovoCure, OncoC4, Onconova, Regeneron Pharmaceuticals, RepImmune, R Pharm, Roche Diagnostics, Seattle Genetics (SeaGen), Sorrento, Sutro Biopharma, Tarveda Therape tics, Toray, Trillium, Umoja, Verastem, VBL Therapeutics, Vincerx Pharma, Xencor, Zentalis. Institution received funds for research: AbbVie, Advaxis, Agenus, AlkermesAravive, Aravive, Arcus Biosciences, AstraZeneca, BeiGene USA, Boston Biomedical, Bristol Myers Squibb, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono, Exelixis, Genentech, Genmab, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche, ImmunoGen, Incyte Corporation, IOVANCE Biotherapeutics, Karyopharm, Leap Therapeutics, Ludwig Institute, Merck & Co, Merck Sharp & Dohme Corp, Mersana Therapeutics, NCI, Novartis, NovoCure, NRG Oncology, OncoC4, OncoQuest, Pfizer, Precision Therapeutics, Prelude Therapeutics, Regeneron Pharmaceuticals, RTOG, Rubius Therapeutics, Seattle Genetics (SeaGen), Sutro Biopharma, SWOG, TESARO, Verastem. FR: Honoraria from GSK, Pharmamar, Clovis, MSD and Roche. UAM: Consulting or advisory fees: NextCure, Allarity, Ovarian Cancer Research Alliance, Pfizer, Profound Bio, Eisai, CureLab, Immunogen, Trillium, Agenus, Novartis, Boerhinger Ingelheim; participation in a Data Safety Monitoring Board: Alkermes, Symphogen; speakers’ bureau: Med Learning Group. TVG: Consulting/advising with AstraZeneca, Eisai, GSK, ImmunoGen, MSD/Merck, OncXerna Therapeutics, Seagen and Tubulis; travel, accommodations, and/or expenses from AstraZeneca, ImmunoGen, MSD/Merck, and PharmaMar; research funding from Amgen, Roche and AstraZeneca. All payments institutional. GS: research funding from MSD/Merck and honoraria from Clovis Oncology; consultant for Tesaro and Johnson & Johnson. BJM: consulting with Agenus, Akeso Bio, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novocure, Novartis, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL; speakers’ bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Bogani, G., et al. (2020). "Adjuvant chemotherapy vs. observation in stage I clear cell ovarian carcinoma: A systematic review and meta-analysis." Gynecologic Oncology 157(1): 293-298.
	The role of adjuvant chemotherapy in surgically staged stage I clear cell ovarian cancer (OCCC) is unclear. Here, we performed a systematic review and meta-analysis in order to evaluate the role of chemotherapy vs. observation in stage I OCCC. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; ID: #129628). A protocol was defined prior to the search include the population criteria, description of interventions, comparisons, and the outcomes of interest, according to the PRIMA guidelines. Overall, the study population included 5073 women. Stage I OCCC experienced a 5-year disease-free survival and a 5-year overall survival of 83.7% and 86.9%, respectively. Pooled data suggested that in the overall population adjuvant chemotherapy did not impact on 5-year disease free survival (test for overall effect, Z = 0.18; p = 0.86) and 5-year overall survival (test for overall effect, Z = 0.62; p = 0.53). Focusing on 2264 stage IC OCCC we observed that adjuvant correlated with an improvement in overall survival (OR: 0.70 (95%CI: 0.52 to 0.93); Z = 2.44; p = 0.01). In conclusion our study underlines that adjuvant chemotherapy could be reserved for patients with stage IC OCCC; while in stage IA and IB it could be safely omitted. Owing to the inherent biases of the studies included in the meta-analysis further prospective evidences are needed.; Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. No funding sources supported this investigation. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bogani, G., et al. (2024). "Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer." Annals of oncology : official journal of the European Society for Medical Oncology.
	Background: Immunotherapy has transformed the endometrial cancer treatment landscape , particularly for those exhibiting mismatch repair deficiency (MMRd/MSI-H). A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed.; Materials and Methods: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer.; Results: The pooled data from 2,320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone (Hazard Ratio (HR): 0.70, 95% Confidence Interval (CI): 0.62, 0.79) across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n=563; HR: 0.33, 95% CI: 0.23, 0.43). This benefit, albeit less robust, persists in the MMRp/MSS group (n=1,757; HR: 0.74, 95% CI: 0.60, 0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR: 0.75, 95% CI: 0.63, 0.89). However, overall survival data maturity remain low.; Conclusions: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials. (Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Bogani, G., et al. (2023). "Selinexor in patients with advanced and recurrent endometrial cancer." Current problems in cancer 47(6): 100963.
	Selinexor is an oral inhibitor of the nuclear export protein called Exportin 1 (XPO1) with demonstrated antitumor activity in hematological and solid tumors. Selinexor, blocking XPO1, induces nuclear localization of tumor suppressor proteins (including p53, p73, BRCA1, and pRB), leading to the selective induction of apoptosis, and inhibition of DNA damage repair proteins. XPO1 overexpression is common in endometrial cancers. Phase I and II trials reported the antitumor activity of selinexor in patients with endometrial carcinoma. The preliminary results of the phase III Selinexor in ENDOmetrial Cancer (SIENDO/ENGOT-EN5/GOG-3055) trial supported the use of selinexor as maintenance therapy in advanced endometrial cancer patients achieving at least partial response after a minimum of 12 weeks of first-line platinum-based chemotherapy. Selinexor maintenance resulted in a (nonsignificant) 30% reduction in the risk of disease progression or death. Looking at the endometrial cancer molecular subgroup characterized by TP53 wild type, the antitumor activity of selinexor seemed more pronounced, resulting in approximately a 60% reduction in the risk of disease progression or death. The SIENDO and the XPORT-EC trials will clarify the benefits and risks of adding selinexor as a first-line chemotherapy maintenance treatment in all-comer and TP53 wild-type endometrial cancers. Preclinical data highlights the potential for selinexor to be synthetically lethal with PARP inhibitors and may also plan a role in overcoming acquired resistance to those therapies. Therefore, new possible combinations with PARP inhibitors and should be evaluated. Furthermore, the combination of selinexor plus immune checkpoint inhibitors deserves further investigation in clinical trials.; Competing Interests: Declaration of Competing Interest Giorgio Bogani: Novartis AG Pharma (C/A, H), Italian Ministry of Health (RG); Bradley J Monk: AstraZeneca (SH, SAB), GSK (SH, SAB), Incyte (SAB), Merck (SH, SAB), Roche/Genentech (SH, SAB), Eisai (SAB), GOG-Foundation (E), US Oncology (E); Ana Oaknin: Roche (SAB), AstraZeneca (SAB), PharmaMar (SAB), Clovis Oncology (SAB), Tesaro (SAB), ImmunoGen (SAB), Genmab (SAB), Mersana (SAB), GSK (SAB), Deciphera (SAB), AGENUS (SAB), Corcept Therapeutics (SAB), Eisai (SAB), EMD Serono (SAB), Medison (SAB), Merck Sharp and Dohme (SAB), Novocure, prIME Oncology (SAB), Shattuck Labs (SAB), Sutro Biopharma (SAB), ITeos Therapeutics(SAB), Amgen (SAB), Karyopharm Therapeutics (RF); Ignace Vergote: Consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis. Contracted research (via KULeuven) Oncoinvent AS Corporate sponsored research: Amgen, Roche Accommodations, travel expenses: Karyopharm, Genmab, Novocure; Bruno Bolognese: Karyopharm Therapeutics (OI). The other authors indicated no financial relationship. Legend: consulting/advisory relationship (CA); speaker honoraria (SH); honoraria (H); research funding (RF); ownership interest (OI); intellectual propriety/patent holder (IP); scientific advisory board (SAB). (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bogani, G., et al. (2019). "Sentinel node mapping vs. lymphadenectomy in endometrial cancer: A systematic review and meta-analysis." Gynecologic Oncology 153(3): 676-683.
	Sentinel node mapping is increasingly being utilized for endometrial cancer staging. However, only limited evidence supporting the adoption of sentinel node mapping instead of conventional lymphadenectomy is still available. Here, we aimed to review the current evidence comparing sentinel node mapping and lymphadenectomy in endometrial cancer staging. This systematic review was registered in the International Prospective Register of Systematic Reviews. Six comparative studies were included. Overall, 3536 patients were included: 1249 (35.3%) and 2287 (64.7%), undergoing sentinel node mapping and lymphadenectomy, respectively. Pooled data suggested that positive pelvic nodes were detected in 184 out of 1249 (14.7%) patients having sentinel node mapping and 228 out of 2287 (9.9%) patients having lymphadenectomy (OR: 2.03; (95%CI: 1.30 to 3.18); p = 0.002). No difference in detection of positive nodes located in the paraaortic was observed (OR: 93 (95%CI: 0.39 to 2.18); p = 0.86). Overall recurrence rate was 4.3% and 7.3% after sentinel node mapping and lymphadenectomy, respectively (OR: 0.90 (95%CI: 0.58 to 1.38); p = 0.63). Similarly, nodal recurrences were statistically similar between groups (1.2% vs. 1.7%; OR: 1.51 (95%CI: 0.70 to 3.29); p = 0.29). In conclusion, our meta-analysis underlines that sentinel node mapping is non-inferior to standard lymphadenectomy in term of detection of paraaortic nodal involvement and recurrence rates (any site and nodal recurrence); while, focusing on the ability to detect positive pelvic nodes, sentinel node mapping could be consider superior to lymphadenectomy. Further randomized studies are needed to asses long term effectiveness of sentinel node mapping. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bogani, G., et al. (2023). "An update on current pharmacotherapy for vulvar cancer." Expert Opinion on Pharmacotherapy 24(1): 95-103.
	Introduction: Limited data on the role of pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer are available.; Areas Covered: This article aims to provide an overview of the current treatment options for patients with vulvar cancer. PubMed (MEDLINE), Embase, CENTRAL, Scopus, and Web of Science databases, as well as ClinicalTrials.gov were searched to review the current evidence as well as future perspectives on the role of pharmacotherapy in patients with vulvar carcinoma.; Expert Opinion: There has been no consensus on the pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer. Concurrent platinum-based chemoradiation is the most widely used treatment modality for primary treatment or for neoadjuvant settings. Chemotherapy in metastatic disease is considered a palliative treatment. Anti-EGFR tyrosine kinase inhibitors seem to show promising anti-tumor activity in patients harboring EGFR alteration. Similarly, growing evidence supports the adoption of immune checkpoint inhibitors in both neoadjuvant and metastatic settings. Molecular and genomic profiling is advocated to identify target mutations. The PI3K/AKT/mTOR and HER/ErbB pathways might represent two intriguing treatment options. Treatments directed against HPV are discussed as well. Further evidence is warranted to identify the best treatment modalities for patients with locally advanced, recurrent, and metastatic disease.

Bogers, S. J., et al. (2021). "Current evidence on the adoption of indicator condition guided testing for HIV in western countries: A systematic review and meta-analysis." EClinicalMedicine 35: 100877.
	BACKGROUND: Indicator condition (IC) guided testing for HIV is an effective way to identify undiagnosed people living with HIV, but studies suggest its implementation is lacking. This systematic review provides an overview of the adoption of IC-guided testing in Western countries. METHODS: Seven ICs were selected: tuberculosis (TB), malignant lymphoma, hepatitis B, hepatitis C, cervical/vulvar carcinoma/intraepithelial neoplasia grade 2+ (CC/CIN2+, VC/VIN2+), and peripheral neuropathy (PN). Embase and Ovid MEDLINE were searched up to November 20th, 2020. Publications of all types, using data from ≥2009, reporting on HIV test ratios in patients ≥18 years in all settings in Western countries were eligible. HIV test ratios and positivity were reported per IC. A random effects-model for proportions was used to calculate estimated proportions (ES) with 95% CIs. This study was registered at PROSPERO, registration number CRD42020160243. FINDINGS: Fifty-seven references, including 23 full-text articles and 34 other publications were included. Most (28/57) reported on HIV testing in TB. No reports on HIV testing in VC/VIN2+ or PN patients were eligible for inclusion. Large variation in HIV test ratios was observed between and within ICs, resulting from different testing approaches. Highest HIV test ratios (pooled ratio: 0·72, 95%CI 0·63-0·80) and positivity (0·05, 95% CI 0·03-0·06) were observed among TB patients, and lowest among CC/CIN2+ patients (pooled ES test ratio: 0·12, 95%CI 0·01-0·31, positivity: 0·00, 95%CI 0·00-0·00). INTERPRETATION: IC-guided HIV testing is insufficiently implemented in Western countries. The large variation in test ratios provides insight into priority areas for implementing routine IC-guided HIV testing in the future. FUNDING: HIV Transmission Elimination in Amsterdam (H-TEAM) consortium and Aidsfonds (grant number P-42,702).

Boguszewski, D., et al. (2021). "Effectiveness of kinesiotaping for the treatment of menstrual pain." Physiotherapy quarterly 28(4): 20‐24.
	Introduction. dysmenorrhoea is a common gynaecological problem among teenage and young adult females. The aim of this work was to evaluate the effectiveness of kinesiotaping for treating menstrual pain. Methods. The subjects were 44 women with complaints of pain during menstruation. The participants were randomly assigned to 3 groups: group 1 (n = 16), in which a kinesio tape was applied to the abdominal area; group 2 (n = 14), in which an identically looking inelastic tape was applied; and group 3 (n = 14), in which no intervention occurred. The degree of menstrual discomfort was assessed by a visual analogue scale, modified Laitinen questionnaire, and Spielberger state‐trait anxiety inventory. Results. in all groups, within 24 hours after tape application, pain intensity diminished by approximately 50%. in groups 1 and 2, the reduction of pain occurred 2‐4 hours after the application of the tapes. in contrast, in group 3, an initial increase of pain intensity was observed, and pain decrease began after 11 hours. However, the differences between the groups did not reach statistical significance. The values obtained with the Laitinen pain questionnaire revealed that kinesiotaping significantly reduced the intensity (p = 0.004) and incidence (p = 0.006) of menstrual pain between the first and fifth day. Conclusions. Painful menstruation severely limits everyday functioning. The application of a kinesio tape to the abdominal area may reduce the severity of pain in women with complaints referring to menstruation.

Bohn, J., et al. (2021). "Does obesity influence the preferred treatment approach for early-stage cervical cancer? A cost-effectiveness analysis." Gynecologic Oncology 162(Supplement 1): S142.
	Objectives: Obesity is a major public health concern and can have a negative impact on surgical outcomes. In 2018, a large, randomized control trial evaluated outcomes of minimally invasive radical hysterectomy (MIH) versus open abdominal radical hysterectomy (TAH) for treatment of early stage cervical cancer finding lower rates of disease free and overall survival in TAH. Regarding cost, previous studies have investigated outcomes and costs between MIH and TAH as well as between primary radiation and TAH, yet limited data exists on the outcomes and cost effectiveness of these treatments when compared among different body mass index (BMI) levels. The objective of this study was to examine how outcomes varied by BMI between treatment options for early stage cervical cancer and to ascertain which option was cost effective. Method(s): A Markov decision analytic model was designed using TreeAge Pro software to compare the outcomes and costs of primary radiation versus surgery in women with stage IA1-IB1 cervical cancer. We used a theoretical cohort of 6,000 women who were definitively treated with either (1) TAH, (2) MIH, or (3) primary radiation therapy. We compared results for three BMI ranges: <30 kg/m2, 30-39.9 kg/m2, and >=40 kg/m2. Model inputs were derived from the literature and the model was run over a 5-year time period. Outcomes included complications, recurrence, death, costs, and quality-adjusted life years (QALYs). Sensitivity analyses were performed to determine the robustness of the results. An intervention was deemed cost effective with an incremental cost-effectiveness ratio (ICER) of less than $100,000 per QALY. [Formula presented] Results: Among our cohort of 6,000 women with stage IA1-IB1 cervical cancer, TAH was associated with fewer cervical cancer recurrences and deaths compared to MIH; however, TAH resulted in more complications at each BMI level. Surgical complications outnumbered radiation-related complications as BMI increased. Recurrence rates were similar between TAH and radiation therapy, while there were more deaths associated with surgery. Comparing TAH to MIH, women with a BMI less than 30 had an ICER of $6,800 per QALY and women with a BMI 30-39.9 had an ICER of $739 per QALY. In women with a BMI >= 40, TAH was dominant. Comparing TAH to radiation therapy, women with a BMI less than 30 had an ICER of $191,000/QALY and women with a BMI 30-39.9 had an ICER of $133,000/QALY, which were not cost effective. In women with a BMI >= 40, the ICER was $88,000/QALY, making radiation therapy cost effective. Conclusion(s): Increasing BMI affects surgical morbidity as well as cost effectiveness of treatment modality for early stage cervical cancer. We found that at a BMI >= 40, TAH is both cost effective and provides cost savings when compared to MIH. When compared to primary radiation, TAH is cost effective at a BMI < 30 and 30-39.9. When the BMI is >= 40, primary radiation becomes cost-effective. This suggests that for women with early stage cervical cancer with the greatest BMI, primary radiation may be the optimal management strategy.Copyright © 2021 Elsevier Inc.

Boisbouvier, S., et al. (2022). "Upright patient positioning for pelvic radiotherapy treatments." Technical Innovations and Patient Support in Radiation Oncology 24: 124-130.
	Radiotherapy is typically delivered in supine position. However, upright positioning may affect organ volume, positioning, and movement, compared to supine/prone positioning which might have beneficial impacts. In this study, we report patient positioning data in an upright positioning system designed by Leo Cancer Care. Sixteen patients with pelvic tumors were included in this study. They had 3 setups in an upright position: an initial setup with acquisition of reference optical images, and 2 repositioning setups. The intra-fraction motion was assessed during two 20-minute chair rotation sessions. The patient comfort in supine and upright position was assessed with a 5-point Likert scale questionnaire. Eight women and 8 men treated on regular linacs between October 2021 and June 2022 were included. Their median age and weight were 62.5 years (35 to 81 years) and 75.1 kg (41 to 107 kg). The inter-fraction shift means were -0.5 mm (SD = 2.5), -0.4 mm (SD = 1.3) and -0.9 mm (SD = 2.7) in left-right (LR), antero-posterior (AP), and cranio-caudal (CC) directions, respectively. The intrafraction shifts after 20 min were 0.0 mm (SD = 1.5), 0.2 mm (SD = 1.1) and 0.0 mm (SD = 0.3) in LR, CC, and AP directions, respectively. Average global comfort was 4.1 (3 to 5) for the upright position and 3.9 (2 to 5) for the supine position. In conclusion, the first study on pelvic cancer patients positioned in upright position on a chair is promising, and it opens a potential new direction for the treatment of cancer patients. Evaluation of thoracic and head and neck tumors is ongoing, and imaging with vertical CT is expected to start soon.Copyright © 2022

Bojie, F., et al. (2022). "Survival After Minimally Invasive Radical Hysterectomy With Protective Colpotomy for Cervical Cancer: A Systematic Review and Meta-Analysis."
	
Bok, S. K., et al. (2022). "Body Fluid Trend and Prevalence of Lymphedema after Gynecological Cancer Surgery." Lymphatic Research and Biology 20(2): 185-190.
	Background: This study aimed at understanding the trend in extracellular fluid (ECF) change and estimating the efficacy of the early complex decongestive therapy (CDT) program in terms of prevalence of lower limb lymphedema, as well as at identifying the quality of life (QoL) associated with response to CDT after gynecological cancer therapy. Methods and Results: Thirty-one patients undergoing gynecological cancer treatment were enrolled and randomly assigned to the CDT and control groups. In the CDT group, CDT was started within 2 weeks after surgery for 30 minutes a day, for 2 weeks (5 days per week). The patients' QoL was assessed through the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire; version 3. Inbody S10 (Biospace, Seoul, South Korea) was used to calculate the ECF. The assessment was performed at pre-and post-surgery and at 3, 6, and 12 months after surgery. Statistically significant differences, in favor of the CDT group, were encountered at the 3-month follow-up visit, especially with respect to the QoL score. Regarding the prevalence of lymphedema, no significant difference was observed between groups. The mean value of the impedance ratio was low in the CDT group during the entire 12 month follow-up. Conclusion(s): The results of the present study show that early CDT had a positive effect on the prevalence of lymphedema and body composition. Long-Term follow-up studies with a larger sample size are needed to warrant the time-group effect of early rehabilitation.© Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.

Bologna, I. A. O.-U. d. (2022). Electrochemotherapy With Carboplatinum Plus Bleomycin Versus Bleomycin Alone in Vulvar Cancer.
	No Results Available Drug: Carboplatin|Drug: Bleomycin Compare Local progression-free survival|Compare Health-Related Quality of life (HR-QoL) in patients undergoing BLM + AUC2-CARBOPLATIN vs BLM alone assessed with questionnaires in patients undergoing BLM + CBP vs BLM alone assessed with questionnaires.|Compare Health-Related Quality of life (HR-QoL) in the two study arms assessed with the EQ-5D-5L (5-level EQ-5D version) questionnaire.|Compare Health-Related Quality of life (HR-QoL) in the two study arms assessed with the FACT-V (Functional Assessment of Cancer Therapy-Vulva) questionnaire.|Compare Health-Related Quality of life (HR-QoL) in the two study arms assessed with the FACIT-PAL ( Functional Assessment of Chronic Illness Therapy - Palliative Care) questionnaire.|Compare Overall Survival|Reporting of Adverse Events and Serious Adverse Events Female Phase 2 92 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 41/2022/Farm/AOUBo April 7, 2027

Bologna, I. A. O.-U. d. and P. group (2021). Ketogenic Diet in PCOS With Obesity and Insulin Resistance.
	No Results Available Combination Product: Very low calorie ketogenic diet|Behavioral: Low calorie standard diet Change in Body mass index|Change in body composition measured by bioimpedentiometry|Change in Homeostasis Model Assessment Index|Change in frequency of menstrual cycles|Change in hirsutism|Change in plasma concentrations of testosterone Female Not Applicable 30 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment VLCKD December 6, 2021

Bolt, B. and Inc (2023). Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies.
	No Results Available Drug: BDC-3042|Drug: Pembrolizumab Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0|Incidence and nature of AEs considered by the Investigator or Sponsor to be clinically relevant, attributable to study treatment, and meeting dose-limiting toxicity (DLT) criteria|Objective response rate (ORR) using RECIST 1.1|Duration of response (DOR)|Disease control rate (DCR) of confirmed complete response (CR), partial response (PR), or stable disease (SD) lasting 4 or more weeks|Progression Free Survival (PFS)|Best overall response (CR, PR, SD, progressive disease)|PK (Cmax) of BDC-3042|PK (Cmin) of BDC-3042|PK (AUC0-t) of BDC-3042|PK (AUC0-inf) of BDC-3042|PK (CL) of BDC-3042|PK (Vc or Vss) of BDC-3042|PK (Terminal t1/2) of BDC-3042|Incidence of anti-BDC-3042 antibodies All Phase 1|Phase 2 167 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment BBI-20233042 March 2028

Bolton Virginia, N., et al. (2023). "Human oocyte cryopreservation: revised evidence for practice." Human fertility (Cambridge, England) 26(1): 2-16.
	This article reviews the evidence regarding human oocyte cryopreservation by slow freezing and vitrification and provides evidence-based clinical and laboratory guidelines on the effectiveness and safety of these technologies. The guidelines address the stage of oocyte maturity; cryopreservation and thawing/warming using slow cooling or vitrification; techniques used for insemination of thawed/warmed oocytes; information and support counselling. These are an update of previous guidelines. The following outcome measures were examined: cryosurvival, fertilisation rate, cleavage rate, implantation and clinical pregnancy rate, miscarriage rate, live birth rate, psychosocial wellbeing, health of resulting children. This update does not include recommendations specific to fertility preservation for defined patient groups and specific ovarian stimulation regimens as they are covered in detail in recent guidance from the European Society of Human Reproduction and Embryology (ESHRE).

Bona Alberto, F., et al. (2020). "Incidence, prevalence, and factors associated with lymphedema after treatment for cervical cancer: a systematic review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 30(11): 1697-1704.
	Background: Lower limb lymphedema is a frequent and debilitating complication after cervical cancer treatment.; Objective: To evaluate the incidence and prevalence of lymphedema after treatment for cervical cancer and evaluate the factors associated with this outcome.; Methods: The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Eligible studies were identified through the databases Medline (via PubMed), LILACS, Scopus, and Web of Science. For the search, descriptors, keywords, and synonyms were used for cervical cancer, lymphedema, and outcomes of interest (incidence, prevalence, frequency, occurrence, morbidity, risk factors, and prognosis). Observational studies were included that were published in English, Portuguese, or Spanish, between January 1, 2013 and December 31, 2019, with frequency data and associated factors for lymphedema after cervical cancer treatment. Studies that evaluated the presence of lymphedema less than 6 months after surgery or radiotherapy and those in which frequency data were not stratified by tumor topography, were excluded.; Results: Twenty-three studies were included. The incidence of lymphedema varied between 0% and 69%. Different designs and methods were employed for lymphedema assessment. The main factors associated with lymphedema included extension of lymphadenectomy, number of lymph nodes removed, removal of circumflex iliac lymph nodes, and adjuvant radiotherapy. Other factors associated with lymphedema included cellulitis, lymphocyst formation, increased age, invasive lymph node staging, higher body mass index, and insufficient physical activity.; Conclusions: The frequency of lymphedema after treatment for cervical cancer is variable. The different designs and methodology to measure this complication make it difficult to draw definitive conclusions about its prevalence. The method used for lymphedema assessment is not standardized.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Bonab, V. K., et al. (2023). "The effect of combination exercise training along with ginger supplementation on PGE2 levels and primary dysmenorrhea symptoms in sedentary girls." Iranian Journal of Obstetrics, Gynecology and Infertility 26(9): 29-39.
	Introduction: Primary dysmenorrhea is one of the most common menstrual disorders among women that have a negative impact on their social activities. However, regular exercise training and consumption of medicinal plants is common among women in order to treat primary dysmenorrhea. Therefore, the present study was conducted with aim to investigate the effect of combination exercise training along with ginger supplementation on PGE2 levels and primary dysmenorrhea symptoms (intensity and duration) in sedentary girls. Method(s): In this quasi-experimental study, 60 sedentary young girls with moderate/severe primary dysmenorrhea were randomly placed into one of the four groups: training along with ginger consumption, training along with placebo consumption, ginger and control placebo groups. The training groups performed combination exercise training in two sections of endurance training and strength training. The groups consuming supplementation used ginger capsules. The severity of pain dysmenorrhea was measured by the visual analog scale (VAS) and duration of pain by Cox menstrual cycle (CAS). PGE2 of all participants was examined in two stages before and after the research. Data were analyzed by SPSS software (version 23) and ANCOVA, paired t-test and non-parametric tests. P<0.05 was considered significant. Result(s): The PGE2 level significantly decreased in the groups of training with ginger, training with placebo and ginger (P<0.05). In addition, a significant reduction in the intensity and duration of dysmenorrhea pain was observed in all the intervention groups compared to the placebo group in the second and third cycle of menstruation. Also, a significant difference was found between the two training groups with the supplement and placebo consumption in the pain intensity values (P<0.05). Conclusion(s): Consumption of ginger supplementation and combination exercise training through reducing PGE2 levels can improve the symptoms of primary dysmenorrhea in sedentary girls; it seems that combination of ginger supplement and combination exercise training have the synergistic effect.Copyright © 2023, Mashhad University of Medical Sciences. All rights reserved.

Bonaca Marc, P., et al. (2023). "Left Ventricular Ejection Fraction in Patients With Ovarian Cancer Treated With Avelumab, Pegylated Liposomal Doxorubicin, or Both." The Oncologist 28(10): e977-e980.
	In the phase III JAVELIN Ovarian 200 trial, 566 patients with platinum-resistant/refractory ovarian cancer were randomized 1:1:1 to receive avelumab alone, avelumab plus pegylated liposomal doxorubicin (PLD), or PLD alone. Cardiac monitoring was included for all patients. We report left ventricular ejection fraction (LVEF) data from the trial. Grade ≥3 cardiac adverse events (AEs) occurred in 4 (2.1%), 1 (0.5%), and 0 patients in the avelumab, combination, and PLD arms, respectively. LVEF decreases of ≥10% to below institutional lower limit of normal at any time during treatment were observed in 1 (0.8%), 3 (1.9%), and 2 (1.5%) patients, respectively; 4 had subsequent assessments, and these showed transient decreases. No patient had a cardiovascular AE related to LVEF decrease. This analysis is, to our knowledge, the first analysis of LVEF in patients receiving immune checkpoint inhibitors.; Clinicaltrials.gov Identifier: NCT02580058. (© The Author(s) 2023. Published by Oxford University Press.)

Bondar, O. V., et al. (2021). "The impact of hyperthermic intraperitoneal chemotherapy and cytoreductive surgery on clinical outcomes and quality of life of patients with peritoneal carcinomatosis." Contemporary oncology (Poznan, Poland) 25(4): 270-278.
	AIM OF THE STUDY: To investigate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) on the clinical and oncological outcomes and quality of life (QOL) of patients with peritoneal carcinomatosis (PC). MATERIAL AND METHODS: The study involved 304 patients with PC of different origin, who were divided into 2 groups: Group I - cytoreductive surgery (CRS) + adjuvant chemotherapy (ACT) - 247 patients; Group II - CRS + HIPEC + ACT - 57 patients. Intraoperative characteristics and postoperative complications were compared. Patients' QOL was assessed at all phases of treatment using the international scales the Short Form-36 Health Survey (SF-36) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Breast Cancer Core 30 (EORTC QLQ-C30). RESULTS: No statistically significant differences were observed between the 2 groups comparing the average blood loss and the total rate of postoperative complications, although the rates of hyperthermia and acute renal failure in the early postoperative period were higher in the HIPEC group. The use of HIPEC significantly contributed to the worse restoration of intestinal function in the postoperative period and to prolonged hospital stay. Assessment of the QOL of patients in Group II using SF-36 showed no significant difference between the physical and psychological components of health compared with the control group. The analysis of EORTC data showed a significant deterioration in the QOL of patients in Group II due to increased scales of pain, nausea and vomiting, and constipation in the early postoperative period. No difference in QOL was observed in the subsequent phases of treatment and after its completion. Overall survival and disease-free survival of patients with ovarian cancer who underwent HIPEC were significantly better compared with CRS + ACT alone. CONCLUSIONS: The proposed HIPEC technique has demonstrated its clinical safety in the treatment of PC, no long-term negative impact on the QOL of patients, and better oncological results for ovarian cancer.

Boned-López, J., et al. (2021). "Severe pain during hysterosalpingo-contrast sonography (HyCoSy): a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 304(6): 1389-1398.
	Purpose: To assess the frequency of severe pain perception during hysterosalpingo-contrast sonography (HyCoSy) in infertile women and to assess whether there are differences in the frequency of associated pain according to the contrast used.; Design: Systematic review and meta-analysis.; Patients: Women undergoing HyCoSy due to infertility.; Interventions: Searches were carried out in two databases (Pubmed and Web of Science). We included prospective or retrospective cohort observational studies that specified the type of contrast used during HyCoSy and reported data regarding the number of patients who perceived severe pain during the procedure and the scale used for pain perception score.; Main Outcome Measures: Pooled frequency of severe pain perception during HyCoSy and the pooled frequency of severe pain perception based on the contrast used.; Results: Twenty-nine studies were included in this meta-analysis including a total of 7139 patients. In 10 studies, Saline solution with air was used as contrast EchoVist™ was used in ten studies, in five studies, SonoVue™ was used and in four studies, ExEm-Foam™ was used as contrast. Pooled estimated frequency of severe pain perception during HyCoSy was 6% (95% CI 4-9). No statistically significant differences have been described regarding frequency of severe pain perception in relation to the different contrasts used.; Conclusions: HyCoSy is a tolerable outpatient procedure. We did not find any evidence that one specific contrast was better tolerated than any other was. (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bonner, P. E., et al. (2024). "Osteopathic Manipulative Treatment in Dysmenorrhea: A Systematic Review." Cureus 16(1): e52794.
	The majority of women experience dysmenorrhea during their lifetime. The current standard-of-care treatment consists of nonsteroidal anti-inflammatory drugs, oral contraceptive pills, or intrauterine devices. Osteopathic manipulative treatment (OMT) is a beneficial tool for improving non-musculoskeletal (non-MSK) conditions such as migraines, gastroesophageal reflux disease (GERD), and anxiety. OMT should be utilized to improve other non-MSK conditions, such as dysmenorrhea. The current review aims to evaluate the effects of OMT in women with dysmenorrhea. An extensive search was conducted in Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Biomedical Reference Collection: Comprehensive, and Nursing & Allied Health Collection: Comprehensive from inception to June 2022. Studies evaluating the use of OMT in patients with dysmenorrhea were included, while editorial/opinion articles were excluded. Three independent reviewers evaluated the studies. Ten studies evaluating the use of OMT in patients with dysmenorrhea were included. Overall, OMT was shown to provide relief of symptoms, including back and menstrual pain; however, there was no guideline on which OMT techniques are the most successful. Numerous positive effects were found, including a reduction in the duration of pain, reduction of pain intensity, and reduction of analgesic use. However, the low number of studies supports the need for further investigations. Dysmenorrhea patients could benefit from a prospective randomized controlled trial targeting spinal facilitation and viscerosomatic reflexes to decrease pain duration, pain intensity, and analgesic use. Non-MSK-focused OMT has a large body of mostly anecdotal evidence for relief of conditions such as migraine, GERD, and anxiety. It has helped when traditional standards of care have failed. Non-MSK-focused OMT research represents a relatively untouched field of research that can have a profound and positive global impact, particularly in areas with poor income/healthcare access.

Boo, M., et al. (2022). "Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(2): 189-194.
	Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Boos Elise, W., et al. (2023). "Trends in the Use of Mifepristone for Medical Management of Early Pregnancy Loss From 2016 to 2020." JAMA 330(8): 766.
	
Borčinová, M., et al. (2022). "Challenges in lower limb lymphoedema assessment based on limb volume change: Lessons learnt from the SENTIX prospective multicentre study." Gynecologic Oncology 164(1): 76-84.
	Background: Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation.; Methods: In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery.; Results: Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed.; Conclusions: Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment.; Trial Registration: ClinicalTrials.gov: NCT02494063.; Competing Interests: Declaration of Competing Interest None declared. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bordewijk, E. M., et al. (2023). "Long-term outcomes of switching to gonadotrophins versus continuing with clomiphene citrate, with or without intrauterine insemination, in women with normogonadotropic anovulation and clomiphene failure: follow-up study of a factorial randomized clinical trial." Human reproduction (Oxford, England) 38(3): 421-429.
	Study Question: What are the long-term outcomes after allocation to use of gonadotrophins versus clomiphene citrate (CC) with or without IUI in women with normogonadotropic anovulation and clomiphene failure?; Summary Answer: About four in five women with normogonadotropic anovulation and CC failure had a live birth, with no evidence of a difference in pregnancy outcomes between the allocated groups.; What Is Known Already: CC has long been used as first line treatment for ovulation induction in women with normogonadotropic anovulation. Between 2009 and 2015, a two-by-two factorial multicentre randomized clinical trial in 666 women with normogonadotropic anovulation and six cycles of CC failure was performed (M-ovin trial). This study compared a switch to gonadotrophins with continued treatment with CC for another six cycles, with or without IUI within 8 months. Switching to gonadotrophins increased the chance of conception leading to live birth by 11% over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. The addition of IUI did not significantly increase live birth rates.; Study Design, Size, Duration: In order to investigate the long-term outcomes of switching to gonadotrophins versus continuing treatment with CC, and undergoing IUI versus continuing with intercourse, we conducted a follow-up study. The study population comprised all women who participated in the M-ovin trial.; Participants/materials, Setting, Methods: The participating women were asked to complete a web-based questionnaire. The primary outcome of this study was cumulative live birth. Secondary outcomes included clinical pregnancies, multiple pregnancies, miscarriage, stillbirth, ectopic pregnancy, fertility treatments, neonatal outcomes and pregnancy complications.; Main Results and the Role of Chance: We approached 564 women (85%), of whom 374 (66%) responded (184 allocated to gonadotrophins; 190 to CC). After a median follow-up time of 8 years, 154 women in the gonadotrophin group had a live birth (83.7%) versus 150 women in the CC group (78.9%) (relative risk (RR) 1.06, 95% CI 0.96-1.17). A second live birth occurred in 85 of 184 women (49.0%) in the gonadotrophin group and in 85 of 190 women (44.7%) in the CC group (RR 1.03, 95% CI 0.83-1.29). Women allocated to gonadotrophins had a third live birth in 6 of 184 women (3.3%) and women allocated to CC had a third live birth in 14 of 190 women (7.4%). There were respectively 12 and 11 twins in the gonadotrophin and CC groups. The use of fertility treatments in the follow-up period was comparable between both groups. In the IUI group, a first live birth occurred in 158 of 192 women (82.3%) and while in the intercourse group, 146 of 182 women (80.2%) reached at least one live birth (RR: 1.03 95% CI 0.93-1.13; 2.13%, 95% CI -5.95, 10.21).; Limitations, Reasons for Caution: We have complete follow-up results for 57% of the women.There were 185 women who did not respond to the questionnaire, while 102 women had not been approached due to missing contact details. Five women had not started the original trial.; Wider Implications of the Findings: Women with normogonadotropic anovulation and CC failure have a high chance of reaching at least one live birth. In terms of pregnancy rates, the long-term differences between initially switching to gonadotrophins are small compared to continuing treatment with CC.; Study Funding/competing Interest(s): The original study received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). A.H. reports consultancy for development and implementation of a lifestyle App, MyFertiCoach, developed by Ferring Pharmaceutical Company. M.G. receives unrestricted grants for scientific research and education from Ferring, Merck and Guerbet. B.W.M. is supported by an NHMRC Investigatorgrant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. All other authors have nothing to declare.; Trial Registration Number: This f llow-up study was registered in the OSF Register, https://osf.io/pf24m. The original M-ovin trial was registered in the Netherlands Trial Register, number NTR1449. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Bordon, Y. (2023). "CXCL8 blockade reduces fibrosis in endometriosis." Nature reviews. Immunology 23(4): 203.
	CXCL8 blockade reduces fibrosis in endometriosis Endometriosis is a common condition that leads to pain and infertility, but treatment options are limited. The disease is associated with chronic inflammation, and several inflammatory chemokines have been implicated in its progression. Here, the authors examined the expression of inflammatory genes in endometriotic tissue samples and identified the chemokine CXCL8 (also known as IL-8) and its receptors CXCR1 and CXCR2 as being highly upregulated in women with endometriosis. CXCL8 was also highly expressed in cynomolgus monkeys that spontaneously developed endometriosis, and preliminary experiments suggested that targeting CXCL8 reduced fibrotic disease in these animals. The authors engineered a long-lasting antibody against CXCL8 (AMY109) and showed that therapeutic delivery of this agent reduced disease in a surgically induced model of endometriosis in cynomolgus monkeys. AMY109 seemed to reduce the fibrotic disease associated with endometriosis, at least in part by blocking neutrophil recruitment and activation. The authors report that trials of AMY109 in humans are now underway. Original article: Nishimoto-Kakiuchi, A. et al. A long-acting anti–IL-8 antibody improves inflammation and fibrosis in endometriosis. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abq5858 (2023)

Borghese, G., et al. (2021). "Adhesion barriers in laparoscopic myomectomy: Evidence from randomized clinical trials." International Journal of Gynecology and Obstetrics 152(3): 308-320.
	Objective: To evaluate the effectiveness of different adhesion barriers in the prevention of de novo adhesion development after laparoscopic myomectomy. Method(s): A systematic review was performed by searching seven electronic databases for all randomized clinical trials (RCTs) comparing the use of any absorbable adhesion barrier (i.e. intervention group) with either no treatment or placebo (i.e. control group) in the prevention of adhesion development after laparoscopic myomectomy. Result(s): Eight RCTs with a total of 748 participants (392 in the intervention group and 356 in the control group) were included. The assessed adhesion barrier methods were: oxidized regenerated cellulose (ORC) in two studies, auto-crosslinked hyaluronic acid (HA) gel in two studies, 4% icodextrin solution in one study, modified HA and carboxy-methylcellulose in one study, polyethylene glycol ester trilysine amine solution plus a borate buffer solution in one study, and polyethylene glycol amine plus dextran aldehyde polymers in another study. Conclusion(s): Adhesion barrier methods showing the most promising results were: ORC, auto-crosslinked HA gel, and polyethylene glycol amine plus dextran aldehyde polymers.Copyright © 2020 International Federation of Gynecology and Obstetrics

Borodulina, I. V., et al. (2024). "[Sacral magnetic stimulation in overactive bladder syndrome: comparative analysis of protocols with a frequency of 1 and 5 Hz]." Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury 101(1): 22-29.
	UNLABELLED: Peripheral magnetic stimulation (pMS) has shown its effectiveness in the treatment of lower urinary tract symptoms, such as symptoms of an overactive bladder (OAB). The perineal region (pelvic floor) and the sacral roots area (projection S3 of the root) are used as the locus of stimulation. The published literature presents protocols with different parameters of stimulation, while each of them reliably demonstrates clinical efficacy, however, no comparative studies have been found to select priority stimulation modes when analyzing available sources. OBJECTIVE: To compare the efficacy and safety of different frequency - 1 and 5 Hz - modes of sacral MS in patients with symptoms of OAB. MATERIAL AND METHODS: A single blind prospective randomized comparative clinical study included 59 patients with OAB symptoms. The patients were divided by simple randomization into the group 1 (n=30), which received MS 3 times a week for 5 weeks with a frequency of 1 Hz per sacral root area (S2-S4), and the group 2 (n=29), in which stimulation was performed at a frequency of 5 Hz, while the remaining parameters and duration of therapy were identical to group 1. RESULTS: Sacral pMS with different frequency modes (1 and 5 Hz) is reliably equally effective against the clinical symptoms of OAB, which is confirmed by the absence of significant intergroup differences. In patients receiving MS with a frequency of 5 Hz, there was a more pronounced increase in maximum cystometric capacity, normalization of the maximum and average urine flow velocity and regression of the residual urine volume (p<0.001, p=0.007, p=0.011 and p=0.012 compared with group 1). The greatest difference in indicators was observed in the increase in the maximum cystometric capacity - +31±25 ml at MS with a frequency of 1 Hz and +109±96 ml at MS with a frequency of 5 Hz (p<0.001). MS is a safe procedure and is well tolerated by patients. CONCLUSION: pMS when exposed to the area of S2-S4 roots for 20 minutes 3 times a week with a course for 5 weeks is reliably effective against the clinical symptoms of OAB at different frequency modes (1 and 5 Hz). At the same time, MS with a frequency of 5 Hz may have an advantage over stimulation of 1 Hz in terms of its effect on urodynamic parameters (maximum cystometric capacity, peak and average urine flow velocity and residual urine volume), which may be associated with a large inhibitory effect on detrusor.

Borrego-Jimenez, P. S., et al. (2021). "Improvement in Quality of Life with Pelvic Floor Muscle Training and Biofeedback in Patients with Painful Bladder Syndrome/Interstitial Cystitis." Journal of Clinical Medicine 10(4).
	OBJECTIVE: To prove the benefits of pelvic floor muscle training with biofeedback (BFB) as a complementary treatment in women with bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: Prospective, randomized study in 123 women with BPS/IC. Groups: BFB+ (n = 48): women with oral drug treatment (perphenazine and amitriptyline) plus intravesical instillations (sodium hyaluronate) plus pelvic floor muscle training with BFB; BFB-: (n = 75): women with oral drug treatment plus intravesical instillations. VARIABLES: age, body mass index (BMI), time of follow-up, length of disease, time free of disease, diseases and health conditions concomitant, and responses to the SF-36 health-related quality of life questionnaire at the first consultation (SF-36 pre-treatment), and at the end of the study (SF-36 post-treatment). The treatment was considered successful when the SF-36 score reached values equal to or greater than 80 points or when the initial value increased by 30 or more points. RESULTS: Mean age was 51.62 years old (23-82). BMI was higher in BFB-. The mean length of BPS/IC condition was 4.92 years (1-20), shorter in BFB+ than in BFB-. Mean SF-36 score pre-treatment was 45.92 points (40-58), lower in BFB+ than in BFB-. Post-treatment SF-36 score was higher than pre-treatment SF-36 score both in BFB+ and BFB-. SF-36 values were higher in BFB+ compared to BFB- over the follow-up. CONCLUSIONS: BFB improves quality of life in women with BPS/IC as adjunct therapy to combined oral and intravesical treatment.

Borrelli Eric, P. and G. McGladrigan Conor (2020). "Real-world evidence of poly ADP-ribose polymerase inhibitors in the treatment of ovarian cancer: A systematic literature review." Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 26(8): 1977-1986.
	Objective: The treatment landscape for ovarian cancer has shifted in recent years with the approval of poly ADP-ribose polymerase inhibitors in 2014. Most patients with ovarian cancer have advanced disease at diagnosis. Understanding how treatments for advanced disease work in real-world settings must be assessed to provide care for these patients. Therefore, the objective of this study was to locate and assess real-world studies measuring the safety and effectiveness of poly ADP-ribose polymerase inhibitors and analyze the results. Data sources: A targeted systematic literature review was conducted in April 2020 of PubMed/Medline. Inclusion criteria consisted of observational studies using real-world data of olaparib, rucaparib, or niraparib as an intervention in the treatment of ovarian cancer. In addition, studies needed to assess either clinical effectiveness or safety. Once studies were identified, we aimed to narratively describe the studies' patient population, intervention effectiveness, and/or safety. Data summary: Our systematic review identified six studies assessing the real-world effectiveness and/or safety of poly ADP-ribose polymerase inhibitors, with five assessing olaparib, one assessing poly ADP-ribose polymerase inhibitors as a composite, and none assessing either niraparib or rucaparib. The median progression free survival in the real-world trials for olaparib ranged from 12.7 to 15.6 months. The median overall survival in the real-world trials for olaparib ranged from 30.9 to 35.4 months. Rates of treatment discontinuation due to adverse events for olaparib ranged from 4.4% to 12.5%.; Conclusions: The identified studies showed slightly higher, but comparable results for median progression free survival, median overall survival, and discontinuation due to adverse events compared to the respective randomized controlled trials.

Bosas, J., et al. (2023). "Factors affecting female sexual well-being: A 5-year follow-up of a randomised clinical trial on post-abortion contraception." BMJ Sexual and Reproductive Health: bmjsrh-2023.
	Introduction: Sexual well-being is associated with general well-being. Several factors, such as overweight, infertility, anxiety and sex hormones, also play a role, but the effects of hormonal contraception remain a point of debate. We characterised the factors associated with sexual well-being in fertile-aged women following induced abortion. Method(s): A 5-year follow-up of a nested, longitudinal, cohort study examining the effects of routine provision of intrauterine contraception as part of abortion care. Sexual well-being, anxiety and quality of life were assessed annually using validated questionnaires (McCoy Female Sexuality Questionnaire, State-Trait Anxiety Inventory and EuroQoL), along with data on general and reproductive health, and relationship status. Of the 742 women participating in the trial, 290 (39%) provided sufficient follow-up data and were included in this study. Result(s): Based on trajectories of McCoy scores across the 5-year follow-up, two groups were identified: those with stable and higher (n=223, 76.9%) and those with declining sexual well-being (n=67, 23.1%). Women in the group of declining sexual well-being had significantly higher levels of anxiety and lower quality of life at all time points. They also had chronic diseases more often and were less happy in their relationships. No differences were found in method of contraception when classified as hormonal versus non-hormonal, or long-acting versus short-acting reversible contraception. Conclusion(s): Lower anxiety and higher quality of life are associated with stable and higher sexual well-being. Method of contraception or relationship status are not associated with sexual well-being during long-term follow-up in fertile-aged women.Copyright © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Bosch, E., et al. (2023). "Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial." Human reproduction (Oxford, England).
	STUDY QUESTION: Does ovarian stimulation with highly purified (hp)-HMG protect from elevated progesterone in the follicular phase compared to recombinant FSH (r-FSH) cycles through a different regulation of follicular steroidogenesis? SUMMARY ANSWER: hp-HMG enhanced the Δ4 pathway from pregnenolone to androstenodione leading to lower serum progesterone at the end of the cycle, while r-FSH promoted the conversion of pregnenolone to progesterone causing higher follicular phase progesterone levels. WHAT IS KNOWN ALREADY: Elevated progesterone in the follicular phase has been related to lower clinical outcome in fresh IVF cycles. Progesterone levels are positively correlated to ovarian response, and some studies have shown that when r-FSH alone is used for ovarian stimulation serum progesterone levels on the day of triggering are higher than when hp-HMG is given. Whether this is caused by a lower ovarian response in hp-HMG cycles or to a difference in follicular steroidogenesis in the two ovarian stimulation regimens has not been well characterized. STUDY DESIGN, SIZE, DURATION: A randomized controlled trial including 112 oocyte donors undergoing ovarian stimulation with GnRH antagonists and 225 IU/day of r-FSH (n = 56) or hp-HMG (n = 56) was carried out in a university-affiliated private infertility clinic. Subjects were recruited between October 2016 and June 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The women were aged 18-35 years with a regular menstrual cycle (25-35 days) and normal ovarian reserve (serum anti-Müllerian hormone (AMH) = 10-30 pMol/l) undergoing ovarian stimulation for oocyte donation. FSH, LH, estradiol (E2), estrone, progesterone, pregnenolone, 17-OH-progesterone, androstenodione, dehidroepiandrostenodione, and testosterone were determined on stimulation Days 1, 4, 6, and 8 and on day of triggering in serum and in follicular fluid. Samples were frozen at -20°C until assay. Total exposures across the follicular phase were compared by polynomic extrapolation. MAIN RESULTS AND THE ROLE OF CHANCE: Subjects in both groups were comparable in terms of age, BMI, and AMH levels. Ovarian response was also similar: 17.5 ± 7.9 (mean ± SD) versus 16.5 ± 7.5 oocytes with r-FSH and hp-HMG, respectively (P = 0.49). Serum progesterone (ng/ml) on day of trigger was 0.46 ± 0.27 in the hp-HMG group versus 0.68 ± 0.50 in the r-FSH group (P = 0.010). Differences for progesterone were also significant on stimulation days 6 and 8. The pregnenolone: progesterone ratio was significantly increased in the r-FSH group from stimulation day 8 to the day of trigger (P = 0.019). Serum androstenodione (ng/ml) on day of trigger was 3.0 ± 1.4 in the hp-HMG group versus 2.4 ± 1.1 in the r-FSH group (P = 0.015). Differences in adrostenodione were also significant on stimulation Day 8. The pregnenolone:androstenodione ratio was significantly higher in the hp-HMG group (P = 0.012) on Days 6 and 8 and trigger. There were no other significant differences between groups. Follicular fluid E2, FSH, LH, dehidroepioandrostenodione, androstenodione, and testosterone were significantly higher in the hp-HMG than r-FSH group. No differences were observed for progesterone, estrone, 17-OH-progesterone, and pregnenolone in follicular fluid. LIMITATIONS, REASONS FOR CAUTION: All women included in the study were young, not infertile, and had a normal BMI and a good ovarian reserve. The findings might be different in other patient subpopulations. Hormone analyses with immunoassays are subject to intra-assay variations that may influence the results. WIDER IMPLICATIONS OF THE FINDINGS: Stimulation with hp-HMG may prevent progesterone elevation at the end of the follicular phase because of a different follicular steroidogenesis pathway, regardless of ovarian response. This should be considered, particularly in patients at risk of having high progesterone levels at the end of the follicular phase when a fresh embryo transfer is planned. STUDY FUNDING/COMPETING INTEREST(S): Roche Diag ostics provided unrestricted funding for all serum and follicular fluid hormone determinations. J.L.R., M.M., and A.P. have nothing to declare. E.B. has received consulting fees from Ferring, Merck, Gedeon Richter, and Roche and has participated in a research cooperation with Gedeon-Richter. In addition, the author has participated in speakers' bureau and received fees from Ferring, Gedeon Richter, Merck, and Roche. P.A. has received consulting fees from MSD and has participated in speakers' bureau and received fees from Ferring. P.A. also declares travel/meeting support from MSD. E.L. has received consulting fees from Ferring and MSD. In addition, the author has participated in a research cooperation with Gedeon-Richter. Also, the author has participated in speakers' bureau and received fees from Ferring and IBSA, as well as travel/meeting support from IBSA and Gedeon Richter. E.B., P.A., and E.L. also own stocks in IVIRMA Valencia. TRIAL REGISTRATION NUMBER: NCT: NCT02738580. TRIAL REGISTER DATE: 19 February 2016. DATE OF FIRST PATIENT’S ENROLMENT: 03 October 2016.

Bosdou Julia, K., et al. (2020). "Risk of gestational diabetes mellitus in women achieving singleton pregnancy spontaneously or after ART: a systematic review and meta-analysis." Human Reproduction Update 26(4): 514-544.
	Background: Women who achieve pregnancy by ART show an increased risk of obstetric and perinatal complications compared with those with spontaneous conception (SC).; Objective and Rationale: The purpose of this systematic review and meta-analysis was to synthesize the best available evidence regarding the association between ART and gestational diabetes mellitus (GDM) in women with singleton pregnancies. The research question asked was whether the risk of GDM is higher in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously.; Search Methods: A literature search, in MEDLINE, Scopus and Cochrane databases, covering the period 1978-2019, was performed aiming to identify studies comparing the risk of GDM in singleton pregnancies after ART versus after SC. Both matched and unmatched studies were considered eligible. Meta-analysis of weighted data was performed using the random effects model. Results were reported as risk ratio (RR) with 95% CI. Heterogeneity was quantified with the I2 index.; Outcomes: The study reports on 63 760 women who achieved a singleton pregnancy after ART (GDM was present in 4776) and 1 870 734 women who achieved a singleton pregnancy spontaneously (GDM in 158 526). Women with singleton pregnancy achieved by ART showed a higher risk of GDM compared with those with singleton pregnancy achieved spontaneously (RR 1.53, 95% CI 1.39-1.69; I2 78.6%, n = 37, 1 893 599 women). The direction or the magnitude of the effect observed did not change in subgroup analysis based on whether the study was matched (n = 17) or unmatched (n = 20) (matched: RR 1.42, 95% CI 1.17-1.72; I2 61.5%-unmatched: RR 1.58, 95% CI 1.40-1.78; I2 84.1%) or whether it was prospective (n = 12) or retrospective (n = 25) (prospective studies: RR 1.52, 95% CI 1.27-1.83, I2 62.2%-retrospective studies: RR 1.53, 95% CI 1.36-1.72, I2 82.5%). Regarding the method of fertilization, a higher risk of GDM after ART versus SC was observed after IVF (n = 7), but not after ICSI (n = 6), (IVF: RR 1.95, 95% CI 1.56-2.44, I2 43.1%-ICSI: RR 1.42, 95% CI 0.94-2.15, I2 73.5%). Moreover, regarding the type of embryo transfer (ET), a higher risk of GDM after ART versus SC was observed after fresh (n = 14) but not after frozen (n = 3) ET (fresh ET: RR 1.38, 95% CI 1.03-1.85, I2 75.4%-frozen ET: RR 0.46, 95% CI 0.10-2.19; I2 73.1%). A higher risk of GDM was observed after ART regardless of whether the eligible studies included patients with polycystic ovary syndrome (RR 1.49, 95% CI 1.33-1.66, I2 75.0%) or not (RR 4.12, 95% CI 2.63-6.45, I2 0%), or whether this information was unclear (RR 1.46, 95% CI 1.22-1.75, I2 77.7%).; Wider Implications: The present systematic review and meta-analysis, by analysing 1 893 599 women, showed a higher risk of GDM in women achieving singleton pregnancy by ART compared with those achieving singleton pregnancy spontaneously. This finding highlights the importance of early detection of GDM in women treated by ART that could lead to timely and effective interventions, prior to ART as well as during early pregnancy. (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Bostwick, D. G., et al. (2023). "FIRST-IN-HUMAN PHASE 2 CLINICAL TRIAL OF MULTIPLEX COMBINATION INTRATUMORAL IMMUNOTHERAPY (MCII) IN PATIENTS WITH METASTATIC SOLID CANCER (ABSCOPAL 5001 TRIAL)." Journal for Immunotherapy of Cancer 11(Supplement 1): A801.
	Background Little is known of the synergy of combination intratumoral immunotherapy and ablation. We undertook a Phase 2 trial (Abscopal 5001) for patients with metastatic solid cancer (NCT04713371) to assess the safety and efficacy of cryoablation with concurrent injections of low-dose checkpoint inhibitors and chemotherapy, referred to as Multiplex Combination Intratumoral Immunotherapy (MCII). Methods Twelve patients with metastatic cancer and one with sacral chordoma received at least one intratumoral treatment of MCII, preceded by 3-5 days of oral cyclophosphamide. MCII consisted of CT-guided cryoablation followed by intratumoral injection of ipilimumab, pembrolizumab, and cyclophosphamide. GM-CSF was subcutaneously administered daily for a total of 4 weeks. Treatment was repeated every 4-6 weeks if tumor burden remained stable or reduced as noted by iRECIST criteria. Criteria were modified when follow-up biopsies revealed pathology with minimal or no cancer despite persistent mass(es) on imaging. Results Cancers included prostate (4 patients), sarcoma (2), and 1 each of breast, colon, bladder, uterine cervix, tongue, kidney, and sacral chordoma. Eight patients received at least 3 cycles of treatment, two received 2, and three received 1. All patients tolerated the outpatient procedure well and were discharged within 2 hours. Adverse event rate was 69%, all of which were Grade 1 or 2 except for one with delayed cryosurgical complication. At completion of up to 3 cycles of treatment. partial response (iPR) was observed in 5 patients (38.5%) and stable disease (iSD) in 5 (38.5%), for a disease control rate (iDCR) of 77%; progression was observed in 23%. Disparity between post-treatment imaging and pathologic findings was observed in 4 patients, requiring modification of the iRECIST criteria. Best response ranged from 0-91%, with a mean for responding patients of 38%. Injection site response was observed in 9 (69%), and distal abscopal effect was seen in 4 (31%), including one sarcoma patient with complete abscopal response of lung metastases. Biopsy-confirmed resolution of liver metastases was also noted in the bladder cancer patient. Patients are being followed to determine duration of response. Conclusions MCII appears promising, providing 77% disease control rate with manageable, predominantly low-grade adverse events in patients with metastatic cancer. Modification of iRECIST criteria for intratumoral treatment is needed to redefine the primary treatment site response and accommodate disparities between imaging (positive) and pathologic findings (minimal or negative disease).

Bou, K., et al. (2021). "[Home-based devices for the treatment of female urinary incontinence: A literature review]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 31(4): 186-194.
	OBJECTIVE: Literature review on the home-based options for the conservative management of stress urinary incontinence including biofeedback and weighted vaginal cones.. METHODS: Research was conducted in the Cochrane Library and Pubmed to find articles, published until March 2020, dealing with the conservative management of incontinence. RESULTS: A total of 9 randomized controlled trials were included, 4 concerning biofeedback and 5 concerning vaginal cones. Most of them highlighted the superiority of these three methods compared to the absence of treatment but were not superior compared to the pelvic floor muscles training in the clinic setting. CONCLUSION: Home-based devices for female stress urinary incontinence is a safe and effective treatment for female urinary incontinence. It has not shown superiority to physiotherapist-guided pelvic floor muscle reinforcement and needs more evidence to gain its place as a first line therapeutic option.

Bou, K., et al. (2022). "OAB supraspinal control network, transition with age, and effect of treatment: A systematic review." Neurourology and Urodynamics.
	OBJECTIVE: In light of a better understanding of supraspinal control of nonneurogenic overactive bladder (OAB), the prevalence of which increases with age, functional imaging has gained significant momentum. The objective of this study was to perform a systematic review on the transition of supraspinal control of OAB with age, the effect of therapeutic modalities, and a coordinate-based meta-analysis of all neuroimaging evidence on supraspinal OAB control in response to bladder filling. METHODOLOGY: We performed a systematic literature search of all relevant libraries in November 2021. The coordinates of brain activity were extracted from eligible neuroimaging studies to perform an activation likelihood estimation (ALE) meta-analysis. RESULTS: A total of 16 studies out of 241 were selected for our systematic review. Coordinates were extracted from five experiments involving 70 patients. ALE meta-analysis showed activation of the insula, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate gyrus, and temporal gyrus with a transition of activation patterns with age, using a threshold of uncorrected p < 0.001. Among young patients, neuroplasticity allows the activation of accessory circuits to maintain continence, as in the cerebellum and temporoparietal lobes. Anticholinergics, pelvic floor muscle training, sacral neuromodulation, and hypnotherapy are correlated with supraspinal changes attributed to adaptability and possibly a substratum of an intrinsic supraspinal component. The latter is better demonstrated by a resting-state functional connectivity analysis, a promising tool to phenotype OAB with recent successful models of predicting severity and response to behavioral treatments. CONCLUSION: Future neuroimaging studies are necessary to better define an OAB neurosignature to allocate patients to successful treatments.

Bouchard, C. (2022). "Bleeding Patterns with Use of an Oral Contraceptive Containing Estetrol and Drospirenone: Pooled Analysis of Phase-3 Clinical Trials." Journal of Obstetrics and Gynaecology Canada 44(5): 603.
	Objectives: To evaluate bleeding patterns with use of a 24/4-day novel combined oral contraceptive regimen containing estetrol, a natural estrogen, and drospirenone. Method(s): Bleeding data from two parallel, multicentre, open-label, phase-3 trials (United States/Canada and Europe/Russia) were pooled. Healthy participants aged 16-50 years with body mass index of <=35.0 kg/m2 used estetrol 15 mg/drospirenone 3 mg for up to 13 cycles. Participants reported vaginal bleeding (blood loss requiring use of sanitary protection) or spotting (minimal blood loss, requiring no new use of sanitary protection) on daily diaries. Bleeding outcomes were evaluated in participants that started treatment and had at least 1 evaluable cycle. Mean frequency of scheduled and unscheduled bleeding and/or spotting and median duration of bleeding and/or spotting episodes were calculated. Result(s): Of 3417 participants starting treatment, 3265 were included in the bleeding analysis. Mean reported treatment compliance was >=99%. Across cycles, 87.2-90.4% of participants reported scheduled bleeding/spotting, with a median duration of 4-5 days/cycle. Unscheduled bleeding/spotting frequency decreased from 27.1% in Cycle 1 to <17.5% from Cycle 5 onwards, with a median duration of 3-4 days/cycle and most episodes (62.7%) were spotting-only. Of 2234 women completing 13 cycles, 754 (34%) reported unscheduled bleeding/spotting in only 1 or 2 cycles and 911 (41%) did not report any unscheduled bleeding/spotting. The most common bleeding adverse events (AEs) considered treatment-related were 'metrorrhagia' (159 [4.7%]) and 'vaginal hemorrhage' (101 [3.0%]). One hundred four (3.0%) participants discontinued for a bleeding-related AE. Conclusion(s): Most users of estetrol/drospirenone oral contraceptive experienced a predictable bleeding pattern and limited unscheduled bleeding. Keywords: estetrol; oral contraceptive; bleeding profile; drospirenoneCopyright © 2022

Bouchard, C., et al. (2023). "Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: Pooled data from two phase 3 clinical trials." Journal of Obstetrics and Gynaecology Canada 45(5): 349-350.
	Objectives: To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg (24/4 regimen) on premenstrual and menstrual symptoms. Method(s): We pooled Menstrual Distress Questionnaire (MDQ) data from two open-label, phase-3 trials. The studies enrolled participants aged 16-50 years to use E4/DRSP for up to 13 cycles and included starters (no hormonal contraception use in the prior 3 months) and switchers. Participants completed MDQs at study entry and exit. For this analysis, we evaluated 4 MDQ domains (Pain [6 symptoms]; Water Retention [4 symptoms]; Negative Affect [8 symptoms]; and Impaired Concentration [8 symptoms] by converting raw total scores to t-scores for each domain using the MDQ manual, resulting in minimum domain t-scores ranging from 31-40 and maximum scores from 103-159. We compared changes in premenstrual (4 days before most recent flow) and menstrual (most recent flow) outcomes from baseline to end-of-trial using student's t-test. Result(s): Of 3417 treated participants, 2707 (79.2%) completed both MDQs, of whom 1207 (44.6%) were starters. Across the 4 domains, mean baseline t-scores were in the lower range (45-50). Starters reported improvements for menstrual Pain (-3.41, P <0.0001), premenstrual Water Retention (-2.29, P <0.0001), menstrual Water Retention (-2.58, P <0.0001), premenstrual Negative Affect (-1.77, P <0.0001) and menstrual Negative Affect (-1.72, P <0.0001), but not for premenstrual Impaired Concentration (-0.65, P =0.10) or menstrual Impaired Concentration (-0.44, P =0.32). For switchers, none of the differences were significant. Conclusion(s): Overall, E4/DRSP starters experienced improvements in menstrual pain and premenstrual and menstrual negative affect and water retention symptoms. Switchers showed no change.Copyright © 2023

Bouchard, M. E., et al. (2023). "The use of tissue adhesive in management of genitourinary fistulas: a systematic review and case report." International Urogynecology Journal 34(2): 445-451.
	Introduction and hypothesis: Articles are getting published on the use of tissue adhesive for vesicovaginal fistula. The objective is to carry out a systematic review on their effectiveness and complications. Method(s): A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers screened abstracts and full-text and extracted data independently. A narrative synthesis was conducted given the heterogeneity of studies. Result(s): A total of 1032 studies were identified after searching the database, and 14 articles were included in this systematic review. Of the 84 women included, 12 (14.3%) presented failure or recurrence of their fistula tract. The mean time of follow-up was 11.46 months. The average size of the fistula was 1.05 (range 0.1 to 3.9) cm. Most fistulas (81) included were vesicovaginal fistulas. Nine papers reported the usage of fibrin glue in which only three (6.5%) women reported recurrence of the fistula in a delay of 2 weeks to 26 months. The other studies used cyanoacrylate (14 women) and autologous fibrin injection from the patients' blood (31 women). No significant complications were reported. Complications reported were urinary tract infections in 3 women (3.6%), hematuria in 2 women (2.4%), overactive bladder symptoms in 6 women (7.2%) and septic pelvic thrombosis in one woman (1.2%). Conclusion(s): Tissue adhesive appears to be a promising alternative for management of urogenital fistulas without reported important complications.Copyright © 2022, The International Urogynecological Association.

Boulos, S., et al. (2023). "Management of a Large Endometriotic Nodule of the Right Parametrium Involving the Sacral Roots, Vagina, Rectum and Sigmoid Colon, with Intraoperative Bleeding." Journal of Minimally Invasive Gynecology 30(5): 357-358.
	OBJECTIVE: Deep endometriotic lesions may involve the deep parametrium which is highly vascular and includes numerous somatic and autonomous nerves (1,2). Surgeons who dissect in this area, must always be prepared to deal with major bleeding, and to master the different techniques of hemostasis. The goal of this video is to show the steps of laparoscopic excision of deep endometriotic lesion of the parametrium and the steps taken to control the bleeding encountered from one of the venous branches. DESIGN: Surgical educational video. SETTING: Endometriosis referral center. INTERVENTION: Excision of the endometriotic parametrial nodule and the release of the sacral plexus, with excision of the vaginal involvement, rectal disc excision, and segmental resection of the sigmoid colon. The video shows the excision of a deep endometriosis involving the right parametrium, the mid rectum, the sigmoid colon, and the vagina. The excision of deep endometriosis of the parametrium followed the 10 steps previously described (1). During this procedure, careful dissection of arteries and veins branching from the internal iliac vessels is a crucial step. However, injury of one or more of the vessels can still occur. The movie presents the different techniques used to control the bleeding from a venous injury faced during the dissection around the nodule in the parametrium, including energy use, clips, hem-o-loks, and direct continuous pressure. Of note, hemostatic agents are available, however we have not yet successfully employed them in these circumstances in which large veins were injured. The ultimate solution in our case was the clamping of the injured vessels, allowing meticulous dissection and sectioning of all the feeding vessels, while taking care not to injure the sacral roots which were just beneath these veins. Total operative time was 4 hours. CONCLUSION: Surgery of deep endometriosis involving the sacral plexus may be successfully done laparoscopically. Thorough knowledge of the deep pelvis anatomy is mandatory, and the surgeon should master various techniques of hemostasis, particularly on deep veins.

Boulter, A. C., et al. (2023). "Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies." Cancer Chemotherapy and Pharmacology 92(2): 97-105.
	Purpose: Fenretinide (4-HPR) is a synthetic retinoid that induces cytotoxicity through dihydroceramide production. Safingol, a stereochemical-variant dihydroceramide precursor, exhibits synergistic effects when administered with fenretinide in preclinical studies. We conducted a phase 1 dose-escalation clinical trial of this combination. Method(s): Fenretinide was administered as a 600 mg/m2 24-h infusion on Day 1 of a 21-day cycle followed by 900 mg/m2/day on Days 2 and 3. Safingol was concurrently administered as a 48-h infusion on Day 1 and 2 using 3 + 3 dose escalation. Primary endpoints were safety and maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics and efficacy. Result(s): A total of 16 patients were enrolled (mean age 63 years, 50% female, median three prior lines of therapy), including 15 patients with refractory solid tumors and one with non-Hodgkin lymphoma. The median number of treatment cycles received was 2 (range 2-6). The most common adverse event (AE) was hypertriglyceridemia (88%; 38% >= Grade 3), attributed to the fenretinide intralipid infusion vehicle. Other treatment-related AEs occurring in >= 20% of patients included anemia, hypocalcemia, hypoalbuminemia, and hyponatremia. At safingol dose 420 mg/m2, one patient had a dose-limiting toxicity of grade 3 troponinemia and grade 4 myocarditis. Due to limited safingol supply, enrollment was halted at this dose level. Fenretinide and safingol pharmacokinetic profiles resembled those observed in monotherapy trials. Best radiographic response was stable disease (n = 2). Conclusion(s): Combination fenretinide plus safingol commonly causes hypertriglyceridemia and may be associated with cardiac events at higher safingol levels. Minimal activity in refractory solid tumors was observed. Trial registration number: NCT01553071 (3.13.2012).Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Bourdel, N., et al. (2019). "Systematic review of quality of life measures in patients with endometriosis." PloS One 14(1): e0208464.
	Objectives Endometriosis and quality of life has been the subject of much research, however, there is little consensus on how best to evaluate quality of life in endometriosis, resulting in many and diverse scales being used. In our study, we aim to identify quality of life scales used in endometriosis, to review their strengths and weaknesses and to establish what would define an ideal scale in the evaluation of endometriosis-related quality of life. Materials and methods A search of the MEDLINE and EMBASE databases was carried out for publications in English and French for the period from 1980 to February 2017, using the words 'endometriosis' and 'quality of life'. Publications were selected if they reported on quality of life in patients with endometriosis and specified use of a quality of life scale. A quantitative and a qualitative analysis of each scale was performed in order to establish the strengths and weaknesses for each scale (systematic registration number: PROSPERO 2014: CRD42014014210). Results A total of 1538 articles publications were initially identified. After exclusion of duplicates and application of inclusion criteria, 201 studies were selected for analysis. The SF-36, a generic HRQoL measure, was found to be the most frequently used scale, followed by the EHP-30, a measure specific to endometriosis. Both perform well, when compared with other scales, with scale weaknesses offset by strengths. EHP-5 and EQ-5D also showed to be of good quality. All four were the only scales to report on MCID studied in endometriosis patients. Conclusion For clinical practice, routine evaluation of HRQOL in women with endometriosis is essential both for health-care providers and patients. Both SF-36 and EHP-30 perform better overall with regard to their strengths and weaknesses when compared to other scales.Copyright © 2019 Bourdel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bourdon, M., et al. (2024). "Impact of Endometriosis Surgery on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes: a Systematic Review and Meta-analysis." Reproductive sciences (Thousand Oaks, Calif.).
	Endometriosis-related infertility remains a therapeutic challenge. A burning issue in this field of research is determining whether pre-assisted reproductive technology (ART) surgery may be of some benefit in terms of reproductive outcomes. This systematic review and meta-analysis aimed at comparing ongoing pregnancy rates (OPR) and/or live birth rates (LBR) in patients who underwent endometriosis surgery before ART (IVF/ICSI) in comparison with patients who underwent first-line ART (IVF/ICSI). Searches were conducted from January 1990 to June 2021 on PubMed, Embase, and Cochrane Library using the following search terms: endometriosis, surgery, reproductive outcomes, and IVF/ICSI. The primary outcomes were OPR or LBR. A total of 19 studies were included in the meta-analysis. No statistically significant differences in LBR [0.91[0.63, 1.30]; I 2 = 66%; n = 11], OPR [1.28[0.66, 2.49]; I 2 = 60%; n = 3], and early pregnancy loss rate [0.88[0.62, 1.25]; I 2 = 0%; n = 7] per cycle were found when comparing patients who underwent endometriosis surgery before IVF/ICSI and those who did not. After the exclusion of the studies with high risks of bias, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI [0.53[0.33, 0.86]; I 2 = 30%; n = 4]. These data urge the clinician to carefully weigh the pros and cons before referring infertile patients with endometriosis to surgery before IVF, highlighting the key role of multidisciplinary referral centers. (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Bourdon, M., et al. (2023). "The 'freeze-all' strategy seems to improve the chances of birth in adenomyosis affected women." Fertility and Sterility.
	OBJECTIVE: To compare assisted reproductive technologies(ART) outcomes between fresh versus freeze-all strategies in infertile women affected with adenomyosis. DESIGN: A single-center observational study SETTINGS: University hospital-based research center PATIENTS: Adenomyosis-affected women undergoing blastocyst embryo transfer following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between 01/01/2018 and 31/11/2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). INTERVENTION(S): Women who underwent a freeze-all strategy were compared to those who underwent a fresh embryo transfer (ET) strategy. MAIN OUTCOME MEASURE(S): cumulative live birth rate (LBR) RESULTS: A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR [86 (44.1%) vs. 34 (30.6%), respectively; p = 0.020] and the cumulative ongoing pregnancy rate [88 (45.1%) versus 36 (32.4%), respectively; p = 0.029] were significantly higher in the freeze-all group compared to the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared to fresh ET (OR = 1.80; 95% CI = 1.02-3.16). CONCLUSION: The freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative live birth rates. Our preliminary results suggest that the freeze-all strategy is an attractive option that increase ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Boutas, I., et al. (2021). "The expression of Galectin-3 in endometrial cancer: a systematic review of the literature." Molecular biology reports 48(7): 5699-5705.
	Background: Galectin-3 is part of a protein group called lectins and acts as a multifunctional glycoprotein due to its expression location. Galectin-3 is expressed by different human tissues. It plays a significant role in carcinogenesis and the selection of tumor-related physiological and pathological activities. Galectin-3 has been utilized through the years as a diagnostic and prognostic marker for various types of cancers.; Methods and Results: This review describes the outcomes of some studies on the matter that were selected appropriately through a review of the existing literature. These studies examined the levels of Galectin-3 expression in endometrial carcinomas, the outcomes, and the prognosis of these carcinomas. Two of the studies concluded that high expression of Galectin-3 is associated with a tumor's histological grade, type and depth. This enhanced nuclear Galectin-3 expression might assist in progression to atypia and neoplasia. The other three on the contrary concluded that malignant tumors had a decreased expression of Galectin-3 and that Galectin-3 played a suppressive role in tumor growth.; Conclusions: The part Galectin-3 might potentially have in metastasis of cancers and the offering of a better prognosis for patients is of high importance. To date, there is minimal literature regarding the effects of Galectin-3 and more research is required. (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Bouteaud, J., et al. (2022). "Impact of a 12-minute educational video prior to initial consultation in a Mature Women's Health and Menopause Clinic." Menopause 29(7): 856-860.
	Objectives: Assess acceptability of a 12-minute educational video before menopause clinic consultation and evaluate its impact on knowledge and treatment certainty. Method(s): This was a pre-post intervention study among new patients with vasomotor symptoms (VMS) referred to a menopause clinic in Toronto, Canada. Participants completed electronic questionnaires before and after viewing a 12-minute online video covering menopause facts and VMS treatments. Participants' demographic information and referring provider type were recorded. A 19-item true/false knowledge quiz and validated Decision Conflict Scale (DCS) were administered before and after viewing the video along with a validated Acceptability questionnaire after the video. Demographic information and acceptability were summarized descriptively and independent samples t tests compared knowledge and DCS total and subscores before and after viewing the education module. Multivariable analysis was used to identify factors associated with achieving treatment certainty. Result(s): Seventy-one participants completed pre- and postintervention questionnaires. Mean age was 51.4 +/- 6.0 years and most were White (58/71, 81.7%), had a university degree (24/71, 63.3%) and household income >$90,000 (53/71, 74.6%). After the video, there was significant increase in knowledge score (12.7 +/- 2.1 vs. 16.9 +/- 1.8, P < 0.001) and decrease in all DCS scores (total and five subscores) compared with preintervention scores (P < 0.001). Acceptability was high with 62/71 (87.3%) respondents indicating the tool was useful. Findings were independent of level of education, household income, and referring physician type. Conclusion(s): In a study of predominantly university-educated White women, a 12-minute education module on menopause and VMS treatment was acceptable, there was improved knowledge and decision certainty about VMS treatment.Copyright © 2022 by The North American Menopause Society.

Bowen, S. T., et al. (2021). "Defining mechanisms of recurrence following apical prolapse repair based on imaging criteria." American Journal of Obstetrics and Gynecology 225(5): 506.e501-506.e528.
	BACKGROUND: Prolapse recurrence after transvaginal surgical repair is common; however, its mechanisms are ill-defined. A thorough understanding of how and why prolapse repairs fail is needed to address their high rate of anatomic recurrence and to develop novel therapies to overcome defined deficiencies. OBJECTIVE: This study aimed to identify mechanisms and contributors of anatomic recurrence after vaginal hysterectomy with uterosacral ligament suspension (native tissue repair) vs transvaginal mesh (VM) hysteropexy surgery for uterovaginal prolapse. STUDY DESIGN: This multicenter study was conducted in a subset of participants in a randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Overall, 94 women with uterovaginal prolapse treated via native tissue repair (n=48) or VM hysteropexy (n=46) underwent pelvic magnetic resonance imaging at rest, maximal strain, and poststrain rest (recovery) 30 to 42 months after surgery. Participants who desired reoperation before 30 to 42 months were imaged earlier to assess the impact of the index surgery. Using a novel 3-dimensional pelvic coordinate system, coregistered midsagittal images were obtained to assess study outcomes. Magnetic resonance imaging-based anatomic recurrence (failure) was defined as prolapse beyond the hymen. The primary outcome was the mechanism of failure (apical descent vs anterior vaginal wall elongation), including the frequency and site of failure. Secondary outcomes included displacement of the vaginal apex and perineal body and change in the length of the anterior wall, posterior wall, vaginal perimeter, and introitus of the vagina from rest to strain and rest to recovery. Group differences in the mechanism, frequency, and site of failure were assessed using the Fisher exact tests, and secondary outcomes were compared using Wilcoxon rank-sum tests. RESULTS: Of the 88 participants analyzed, 37 (42%) had recurrent prolapse (VM hysteropexy, 13 of 45 [29%]; native tissue repair, 24 of 43 [56%]). The most common site of failure was the anterior compartment (VM hysteropexy, 38%; native tissue repair, 92%). The primary mechanism of recurrence was apical descent (VM hysteropexy, 85%; native tissue repair, 67%). From rest to strain, failures (vs successes) had greater inferior displacement of the vaginal apex (difference, -12 mm; 95% confidence interval, -19 to -6) and perineal body (difference, -7 mm; 95% confidence interval, -11 to -4) and elongation of the anterior vaginal wall (difference, 12 mm; 95% confidence interval, 8-16) and vaginal introitus (difference, 11 mm; 95% confidence interval, 7-15). CONCLUSION: The primary mechanism of prolapse recurrence following vaginal hysterectomy with uterosacral ligament suspension or VM hysteropexy was apical descent. In addition, greater inferior descent of the vaginal apex and perineal body, lengthening of the anterior vaginal wall, and increased size of the vaginal introitus with strain were associated with anatomic failure. Further studies are needed to provide additional insight into the mechanism by which these factors contribute to anatomic failure.

Boyd, B., et al. (2022). "Surgical Treatment of Stress Urinary Incontinence and Complications Stratified by Race and Ethnicity." International Urogynecology Journal 33(Supplement 2): S296-S297.
	Introduction: Midurethral sling (MUS) is the gold standard for the surgical treatment of stress urinary incontinence (SUI). Despite this, White and Hispanic women are more likely to undergo MUS than Black and Asian women. In the United States, White women undergo surgical treatment at a rate almost five times higher than Black women, however the perioperative complication rate for Black women is twice that of White women. This highlights our limited understanding of the racial and ethnic differences among treatment and outcomes of SUI, which has important implications for the provision of more equitable care. Objective(s): To evaluate racial and ethnic differences in the surgical treatment of SUI and associated complications. Method(s): This is a cross-sectional study of women undergoing surgical treatment for SUI between 2015 and 2020 using data from the American College of Surgeons National Surgical Quality Improvement Program. We included patients with SUI who underwent certain anti-incontinence procedures: open Marshall-Marchetti-Krantz procedure (MMK) or Burch urethropexy (CPT 51840, 51841), laparoscopic Burch urethropexy (CPT 51990, 51992) and sling (fascia and synthetic mesh CPT 57288). Complications were evaluated individually and with Clavien Dindo classification, and included mesh erosion, sling revision, blood transfusion, thrombosis, urinary tract infection and readmission within 30 days. Logistic regression models controlling for age, comorbidities and concurrent hysterectomy were used to assess associations between race/ethnicity and type of anti-incontinence procedure and 30-day postoperative complications. Result(s): A total of 23,193 eligible surgical cases were identified, including 223 (1.0%) open MMK/Burch urethropexy, 366 (1.6%) laparoscopic Burch urethropexy, and 22,604 (97.5%) slings. The population was 59.4% Non-Hispanic White, 11.7% Hispanic, 3.4% Non-Hispanic Black, 2.7% Asian, 0.6% Native Hawaiian or Pacific Islander, 0.6% American Indian or Alaska Native, and 21.6% Unknown. In bivariate analysis, American Indian or Alaska Native women were more likely to have an open MMK/Burch urethropexy compared to White women (2.2% vs 1.0%; p<.0001). Black women were more likely to have an open MMK/ Burch urethropexy compared to White women (1.5% vs 0.6%; p<.0001). Native Hawaiian or Pacific Islander women were more likely to have a laparoscopic Burch urethropexy compared to White women (4.7% vs 1.6%; p<.0001). In multivariate analysis, Black and Hispanic women had lower odds of receiving a sling than White women (OR=0.58 and 0.74; p=0.0068 and 0.0181 respectively). American Indian and Alaska Native women were two times more likely as White women to have surgical complications (OR 2.36, CI 1.29-4.31; p= 0.0052). Three percent of American Indian or Alaska Native women were readmitted compared to 1.4% of White women (p= 0.0528). Conclusion(s): In a large, national database, we describe racial and ethnic differences in the treatment of SUI and postoperative complications. Specifically, minority women were more likely to undergo open anti-incontinence procedures and were less likely to undergo sling procedures compared to White women. American Indian or Alaska Native women had higher risk of complications compared to White women. These racial/ethnic differences suggest potential areas of intervention for mitigating health disparities.

Boyd, B., et al. (2023). "TREATMENT FOR STRESS URINARY INCONTINENCE STRATIFIED BY RACE AND ETHNICITY." Neurourology and Urodynamics 42(Supplement 1): S50-S51.
	Introduction: Stress urinary incontinence (SUI) occurs in one in three women over age 45. The prevalence and treatment of SUI vary by race/ethnicity, however there are limitations in the literature. We aim to describe the treatment of SUI in a racially/ethnically diverse health maintenance organization. Method(s): This is a retrospective cohort study of patients with a new diagnosis of SUI (ICD-9 625.6 and ICD-10 N39.3) within Kaiser Permanente Southern California from 2008-2017. We then identified patients referred to Urogynecology or Urology and received treatment with pessary (CPT 57160, ICD-10 Z96.0), referral for pelvic floor physical therapy (PFPT) or surgery (CPT codes CPT 51715, 57288, 51992, 53500 51840, 51990). Logistic regression models examined the association between race/ethnicity and treatment. Result(s): A total of 67,187 patients with a new diagnosis of SUI were included: 36.7% were Non- Hispanic White, 5.6% Black, 47.5% Hispanic, 0.2% American Indian or Alaska Native, 7.6% Asian, 0.4% Native Hawaiian or Pacific Islander, 1.8% Unknown/ Multiple/Other. Within this cohort 9,074 patients were referred to Urogynecology (85.2%) or Urology (14.8%). Black, Hispanic, and Asian women were less likely to receive a pessary than White women (Table 1). Hispanic and Native Hawaiian or Pacific Islander women were more likely to be referred for PFPT (Table 1). All racial/ ethnic groups (except for American Indian/Alaska Native women) were less likely to receive a midurethral sling (MUS) compared to White women. Hispanic and Asian women were less likely to undergo urethropexy. When comparing no treatment to treatment, all racial/ethnic groups, except American Indian/Alaska Native, were less likely to receive treatment compared to White women. All racial/ethnic groups, except Hispanic and American Indian/Alaska Native, were more likely to receive conservative treatment (pessary and PFPT) compared to White women. Conclusion(s): We describe racial/ethnic differences in the treatment of SUI. Racial minority women were 50% less likely to undergo MUS, commonly posited as the gold standard treatment. Racial minority women were 40 - 100% more likely to receive conservative management, and less likely to receive any treatment, compared to White women. This supports prior studies that describe health disparities between racial/ethnic groups and has important implications for more equitable care. Funding(s): This research was supported by a grant from the Regional Research Committee of Kaiser Permanente Southern California, RRC grant number: KP-RRC-20211002..

Boyd, S. S., et al. (2021). "Pelvic Organ Prolapse Severity and Genital Hiatus Size With Long-Term Pessary Use." Female Pelvic Medicine & Reconstructive Surgery 27(2): e360-e362.
	OBJECTIVES: To evaluate the association between pessary use more than 1 year and change in prolapse severity. METHODS: This is a secondary analysis of a previously published randomized controlled trial of women undergoing office management of pessaries for management of symptomatic pelvic organ prolapse and incontinence. Primary outcome was change in pelvic organ prolapse quantification measurement genital hiatus (GH). Secondary outcomes included change in prolapse stage, type of pessary, size of pessary, number of pessary changes, and duration of use. Baseline data were collected from the earliest documented examination within the hospital record before pessary placement and compared with their final study visit. Demographics were analyzed using descriptive statistics. Student t test and Mann-Whitney tests were used for categorical comparisons. Pearson and Spearman correlation coefficients were used to evaluate change over time. RESULTS: The cohort was 132 predominantly non-Hispanic White (75%) women with symptomatic prolapse >stage 2 (70.5%). All were postmenopausal. Median duration of pessary use was 39.5 months (interquartile range, 17-64.5 months). Genital hiatus (P = 0.014) and prolapse stage (P = 0.001) decreased as duration of pessary use increased. Those with baseline stages ≥3 had a significant decrease in GH as duration of pessary use increased compared with stages <3 (-0.5 cm vs 0 cm, P < 0.001). There was no difference in change in GH when comparing women with baseline GH less than 3 to 3 cm or greater. CONCLUSIONS: Pessary use by women with pelvic organ prolapse causes a change in vaginal anatomy over time as seen by decreasing stage and point GH.

Boyle, B. R., et al. (2023). "The effect of weight loss interventions for obesity on fertility and pregnancy outcomes: A systematic review and meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 161(2): 335-342.
	BACKGROUND: Weight loss could improve fertility, perhaps by reducing insulin resistance. OBJECTIVES: To assess the effect of weight loss interventions on fertility in women with obesity not recruited because of known infertility. SEARCH STRATEGY: Three databases during 1966-2020, trial registry. SELECTION CRITERIA: Randomized controlled trials (RCTs) with a follow-up of 1 year or more, with a mean cohort BMI of 30 kg/m2 or above. DATA COLLECTION AND ANALYSIS: A systematic review and meta-analysis was conducted. The primary outcome was pregnancy. The secondary outcome was weight change. MAIN RESULTS: A total of 27 RCTs (5938 women) were included. Weight loss interventions showed no statistically significant increase in pregnancies compared to control interventions (24 trials, 97 women with pregnancy; risk ratio [RR] 1.43, 95% confidence interval [CI] 0.91-2.23); weight change (mean difference [MD] -2.36 kg, 21 trials, 95% CI -3.17 to -1.55). Compared with low-fat diets, very-low-carbohydrate diets showed no statistically significant effect on women with pregnancy (three trials, 14 women with pregnancy; RR 1.37, 95% CI 0.49-3.84) or weight change (MD -0.32 kg, 95% CI -3.84 to 3.21). CONCLUSIONS: Diet-based weight loss interventions for women with obesity not recruited because of infertility were effective at producing long-term weight loss. The effects on fertility were not statistically significant, but few trials provided data. Weight loss trials should routinely collect fertility outcomes.

Boynukalin Fazilet, K., et al. (2022). "Subcutaneous progesterone administration provides a similar ongoing pregnancy rate compared with intramuscular progesterone administration in hormone replacement therapy frozen embryo transfer cycles." F&S reports 4(2): 165-172.
	Objective: To compare the ongoing pregnancy rates (OPRs) for subcutaneous progesterone (SC-P) to intramuscular progesterone (IM-P) in hormone replacement therapy used in frozen embryo transfer (FET) cycles.; Design: Prospective nonrandomized cohort study.; Setting: Private fertility clinic.; Patients: The study enrolled 224 patients scheduled for hormone replacement therapy (HRT)-FET cycles with SC-P (n = 133) or IM-P (n = 91). The route of P administration was decided according to the patient's preference and accessibility to the hospital. In the first FET cycle of a freeze-all cycle using single blastocyst transfers, a woman aged ≤35 was included.; Main Outcomes: Ongoing pregnancy (OP).; Results: The demographic, cycle, and embryologic characteristics were similar between groups. The clinical pregnancy rates (86/133[64.7%] vs. 57/91[62.6%]); miscarriage rates (21/86 [24.4%] vs. 10/57 [17.5%]), and OPR (65/133 [48.9%] vs. 47/91 [51.6%]) were comparable between the SC-P and IM-P groups. Binary logistic regression for OP as the dependent factor revealed that blastocyst morphology was found to be a significant independent prognosticator (for poor quality embryos adjusted odds ratio, 0.11; 95% confidence interval, 0.029-0.427) and progesterone route (SC-P vs. IM-P) was an insignificant prognosticator (adjusted odds ratio, 0.694; 95% confidence interval, 0.354-1.358).; Conclusions: The OPR for SC-P administration was similar to that for IM-P in HRT-FET cycles. The effect of ET-day P levels may vary regarding the administration route. Randomized controlled trials comparing different P administration routes are needed, and large-scale prospective trials are warranted to evaluate the ET-day P levels on pregnancy outcome. (© 2022 The Authors.)

Bozkurt, I. H., et al. (2022). "On-demand use of fesoterodine: a new paradigm for extended release antimuscarinics." International Urogynecology Journal 33(8): 2127‐2132.
	Introduction and hypothesis: We aimed to compare on‐demand and continuous use of fesoterodine 4 mg concerning efficacy and adverse effects. Methods: A total of 100 patients who were diagnosed with non‐neurogenic overactive bladder (OAB) syndrome were included in the study. All patients were evaluated with MMSE, ICIQ‐SF, SEAPI quality of health and OAB‐V8 questionnaires, at the beginning, 1st month and 4th month. Fesoterodine 4 mg was started for treatment. At the end of the 1st month, patients who obtained benefit from the treatment were 1:1 randomized into two groups. In group 1, fesoterodine 4 mg was given 1 × 1 in a standard manner whereas in group 2 patients took the pills on demand. Both groups were evaluated for efficacy and adverse events at 4 months. Results: Final analyses included 69 patients. At 4‐month follow‐up, OAB‐V8 scores were significantly improved compared to 1 month in both groups. Again at h months, no difference was detected between the two groups for MMSE, ICIQ‐SF and SEAPI scores. In continuous usage group, 4th month MMSE scores were significantly lower than 1st month scores. At 4 months, dry mouth and constipation were lower in the on‐demand group compared to continuous usage group. Conclusions: Compared to standard continuous usage, on‐demand usage of fesoterodine showed similar efficacy with fewer adverse events.

Boztaş, E., et al. (2022). "Comparison of the efficacy of pharmacological and nonpharmacological treatments in women with primary dysmenorrhea: randomized controlled parallel-group study." Ginekologia polska.
	Objectives: To compare the effectiveness of pharmacological (PT) and nonpharmacological treatments (NPT) in women with primary dysmenorrhea (PD) and determine the most effective treatment method.; Material and Methods: We enrolled 85 PD participants with PD who were randomly classified into five groups: pharmacological groups; naproxen sodium (NS) and micronized purified flavanoid fraction (MPFF), nonpharmacological groups; motor imagery focused pelvic floor exercise (MOPEXE) and acupressure, and no treatment group; control. Initial assessment was conducted in all groups on the first day of the menstrual cycle. After the end ofthe third menstrual cycle, the specialist physiotherapist and the obstetrician conducted a final evaluation. Intensity and nature of pain were evaluated with the Short-Form McGill Pain Questionnaire (SF-MPQ), and menstrual attitudes and behaviors were evaluated using the Menstruation Attitude Questionnaire (MAQ).; Results: In the total pain dimension scores, which are the sum of the affective dimension of pain and sensory dimension scores, the pre-post treatment difference was the highest in the mean of the total pain dimension. The highest was for MOPEXE (15.12 ± 4.44), followed by MPFF (7.53 ± 6.8); acupressure (7.47 ± 5.28) and NS (4.47 ± 4.91) showed more significant change than the control group (p = 0.001). The mean difference in visual analog scale (VAS) scores was highest in MOPEXE (4.53 ± 1.5), followed by acupressure (2.35 ± 1.66); MPFF (1.88 ± 1.73) and NS (1.65 ± 1.84) scores were more significant than the control group (p = 0.001). Regarding total pain intensity, the highest was MOPEXE (2.59 ± 0.94), followed by MPFF (1.18 ± 0.88); acupressure (1.06 ± 0.83) and NS (0.82 ± 1.01) scores were more significant compared to the control group (p = 0.001). There was no significant change in the pre-post difference values in the MAQ subparameters: menstruation as deliberate event, menstruating as bothersome event, menstruation as natural event, anticipation and prediction of the onset of menstruation, and denial of any effects of menstruation; menstruation as a natural event resulted in insignificant changes in parameters (p = 0.579, p = 0.074, p = 0.892, p = 0.056, p = 0. 377).; Conclusions: PT and NPT methods in the study were effective in coping with PD-associated pain. MPFF was more effective than the NS group in terms of relieving pain. In terms of pain, MOPEXE and acupressure groups were as effective as PT. The most effective of these treatment methods was the MOPEXE group created by the researcher.

Bradley, H., et al. (2022). "The prevalence of depression in women who experience pregnancy related pelvic girdle pain: A systematic review protocol."
	
Bradley, H. A., et al. (2022). "A NUTRITIONAL APPROACH TO TREATING SYMPTOMS OF ANTENATAL DEPRESSION AND ANXIETY. THE NUTRIMUM TRIAL: A DOUBLE-BLIND, RANDOMISED CONTROLLED TRIAL." Journal of Paediatrics and Child Health 58(SUPPL 2): 23.
	Background: Left untreated, antenatal depression and anxiety can have negative consequences for the mother, her baby and the rest of her family. The efficacy of a broad-spectrum multinutrient (minerals and vitamins) formula was investigated as a possible treatment for symptoms of depression and anxiety during pregnancy. Method(s): Between 13-24 weeks gestation, 88 participants scoring >=13 on the Edinburgh Postnatal Depression Scale (EPDS) were randomised to multinutrients (MN) or an active placebo (AP), containing iodine and riboflavin, for 12 weeks. Seventyone (81%) completed the trial with no group differences in dropouts. The Clinical Global Impression Scale of Improvement (CGII) and the EPDS were the primary outcomes analysed using mixed linear modelling. Result(s): Based on the CGI-I, the MN group demonstrated significantly greater improvement in symptoms over time, compared to the AP group (p < 0.001). Further, presence of personality difficulties reduced the placebo effect and increased the response to multinutrients based on CGI-I ratings. When personality difficulties were present, significantly more participants in the MN group (69%) were rated 'responders' to treatment at 12 weeks than the AP group (51%; OR = 6.667, p = 0.017). Participants rated themselves as 'responders' significantly more so in the MN group (69%) than in the AP group (39%; OR = 3.52, p = 0.011). There were no statistically significant differences between groups on the EPDS over time (p = 0.162) or of treatment-emergent adverse events and side effects. Conclusion(s): Broad-spectrum multinutrients may provide a safe, alternative treatment option for antenatal depression and anxiety and improve global functioning. Multinutrients may be of particular benefit to people with personality difficulties.

Bradley Linda, D., et al. (2019). "Clinical Performance of Radiofrequency Ablation for Treatment of Uterine Fibroids: Systematic Review and Meta-Analysis of Prospective Studies." Journal of laparoendoscopic & advanced surgical techniques. Part A 29(12): 1507-1517.
	Background: Radiofrequency ablation (RFA) has emerged as a safe and effective treatment option for women with symptomatic uterine fibroids and can be delivered by laparoscopic, transvaginal, or transcervical approaches. The evidence regarding typical patient outcomes with RFA has not previously been examined in a comprehensive fashion. Materials and Methods: We performed a systematic review of prospective studies for treatment of uterine fibroids with RFA. Main outcomes were procedure time, patient recovery metrics, change in fibroid volume, symptom severity score (SSS), health-related quality of life (HRQL), and reinterventions. Data were analyzed with random effects meta-analysis and metaregression. Results: We identified 32 articles of 1283 unique patients (median age: 42 years) treated with laparoscopic RFA (19 articles), transvaginal RFA (8 articles), or transcervical fibroid ablation (5 articles). Mean procedure time was 49 minutes, time to discharge was 8.2 hours, time to normal activities was 5.2 days, and time to return to work was 5.1 days. At 12 months follow-up, fibroid volume decreased by 66%, HRQL increased by 39 points, and SSS decreased by 42 points (all P < .001 versus baseline). The annual cumulative rate of reinterventions due to fibroid-related symptoms was 4.2%, 8.2%, and 11.5% through 3 years. Conclusions: RFA of uterine fibroids significantly reduces fibroid volume, provides significant durable improvements in fibroid-related quality of life, and is associated with favorable reintervention rates.

Bradley Megan, S., et al. (2023). "Association Between Enlarged Genital Hiatus and Composite Surgical Failure After Vaginal Hysterectomy With Uterosacral Ligament Suspension." Urogynecology (Philadelphia, Pa.) 29(5): 479-488.
	Importance: The impact of a persistently enlarged genital hiatus (GH) after vaginal hysterectomy with uterosacral ligament suspension on prolapse outcomes is currently unclear.; Objectives: This secondary analysis of the Study of Uterine Prolapse Procedures Randomized trial was conducted among participants who underwent vaginal hysterectomy with uterosacral ligament suspension. We hypothesized that women with a persistently enlarged GH size would have a higher proportion of prolapse recurrence.; Study Design: Women who underwent vaginal hysterectomy with uterosacral ligament suspension as part of the Study of Uterine Prolapse Procedures Randomized trial (NCT01802281) were divided into 3 groups based on change in their preoperative to 4- to 6-week postoperative GH measurements: (1) persistently enlarged GH, 2) improved GH, or (3) stably normal GH. Baseline characteristics and 2-year surgical outcomes were compared across groups. A logistic regression model for composite surgical failure controlling for advanced anterior wall prolapse and GH group was fitted.; Results: This secondary analysis included 81 women. The proportion with composite surgical failure was significantly higher among those with a persistently enlarged GH (50%) compared with a stably normal GH (12%) with an unadjusted risk difference of 38% (95% confidence interval, 4%-68%). When adjusted for advanced prolapse in the anterior compartment at baseline, the odds of composite surgical failure was 6 times higher in the persistently enlarged GH group compared with the stably normal group (95% confidence interval, 1.0-37.5; P = 0.06).; Conclusion: A persistently enlarged GH after vaginal hysterectomy with uterosacral ligament suspension for pelvic organ prolapse may be a risk factor for recurrent prolapse.; Competing Interests: M.S.B. received research support from Hologic, Axonics. K.L.F. received grant support from Valencia Technologies and BlueWind Medical. A.G.V has stock ownership in Ninomed. M.G.G received research grant to RTI as the PFDN DCC from Boston Scientific. The remaining authors have declared they have no conflicts of interest. (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Bradley, W., et al. (2021). "Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO1."  162: S25‐S26.
	Objectives: Newly diagnosed advanced ovarian cancer patients (pts) are at high risk of relapse and 5‐year survival is 30–50%. Delay of recurrence, prolonged survival and, for some pts, increased chance of cure are goals of treatment in this setting. In SOLO1 (NCT01844986; GOG‐3004) pts with advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation (BRCAm) who were in response after first‐line platinum‐based chemotherapy derived significant progression‐free survival (PFS) benefit from maintenance olaparib vs placebo (median 41 months follow‐up; median not reached vs 13.8 months; hazard ratio 0.30; P<.001; Moore et al. NEJM 2018). We report analyses after 5‐years of follow‐up (data cut‐off [DCO]: March 5, 2020), performed to assess the long‐term efficacy and tolerability of maintenance olaparib for newly diagnosed advanced ovarian cancer. Methods: Pts received maintenance olaparib (tablets; 300 mg bid) or placebo for up to 2 years or until progression. PFS and recurrence‐free survival (RFS) were investigator‐assessed by modified RECIST v1.1. An exploratory subgroup analysis of PFS in higher‐risk (stage IV disease, stage III disease with residual disease following primary debulking surgery, inoperable stage III disease, or stage III disease and had undergone interval surgery) and lower‐risk (stage III disease without residual disease following primary debulking surgery) pts was carried out. For pts in complete response at baseline, RFS was defined post hoc as time from randomization to disease recurrence (new lesions by imaging) or death.[Formula presented] Results: A total of 260 pts were randomized to olaparib; 131 to placebo (median treatment duration 24.6 vs 13.9 months, respectively). After a median of 4.8 and 5.0 years of follow‐up, median PFS was 56 vs 14 months in the olaparib and placebo arms, respectively (Table). In the higher‐risk subgroup 42% of olaparib‐arm vs 17% of placebo‐arm pts were free from progression at 5 years; in the lower‐risk subgroup 56% vs 25% of pts, respectively, were progression free at this time point. Among pts in complete response at baseline, risk of disease recurrence or death was reduced by 63%. The safety profile of olaparib was consistent with previous observations. No new cases of myelodysplastic syndrome or acute myeloid leukaemia were reported (previous DCO: olaparib, 3/260 [1%]; placebo, 0/130), and incidence of new primary malignancies remained balanced between arms (olaparib, 7/260 [3%]; placebo, 5/130 [4%]). Conclusions: For pts with a BRCAm and newly diagnosed advanced ovarian cancer, the benefit derived from 2 years of maintenance olaparib was sustained beyond the end of treatment, and after 5 years, almost half of pts were progression free vs 20% with placebo. This benefit was consistent across higher‐ and lower‐risk pts. Over 50% of pts in complete response after first‐line platinum‐based chemotherapy remained free from relapse 5 years after randomization. A total of 5 years of follow‐up is the longest for any PARP inhibitor in this setting and no new safety signals were observed.

Bradley, W. H., et al. (2022). "An open label, nonrandomized, multisite phase II trial combining bevacizumab, atezolizumab, and rucaparib for the treatment of previously treated recurrent and progressive endometrial cancer." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Patients with metastatic recurrent endometrial cancer have limited effective therapies. Single agent pembrolizumab is utilized in mismatch repair deficient (MMRd) patients, while the combination of lenvatinib and pembrolizumab is now more commonly used in MMR intact patients who have progressed after chemotherapy combinations. This trial investigated a novel three drug regimen. Method(s): Patients with recurrent endometrial cancer not amenable to curative intent surgery or radiation after one or two lines of therapy were eligible regardless of histology. This study is a multicenter, open-label, nonrandomized phase II trial. All subjects initially received the three-drug combination of rucaparib, bevacizumab, and atezolizumab. The primary goal of this trial was to estimate the overall response rate in these patients, and secondarily to estimate the progression-free and overall survival of patients treated with this triplet combination. Total enrollment was 30, with the first six subjects participated in a safety lead-in. Treatments until progression, toxicity, or clinician choice. Subjects could continue past progression if, in the estimate of the treating clinician and subject, clinical benefit was being provided. Subjects were eligible for analysis if they received at least one cycle and had one postdose tumor assessment. The ORR assumption was 27% with a lower bound of 14%. Result(s): 30 subjects were enrolled between 07/2019 and 06/2021. Of these 26 were evaluable. Median follow up at cut off was 14.9 months. 23 subjects had clinical benefit, with 1 (4%) with CR, 9 (39%) with PR, and 13 (57%) with stable disease as best response. Overall median event-free (progression or death) was 5.3 (95% CI 2.7-7.9) months and overall survival 13.3 (95% CI NA) months at cut off. Median duration of therapy was 4.4 months (IQR 1.7-7.3), with 4 subjects remaining on study directed therapy at data cut off. Histology distribution was 50% serous, 20% endometrioid, and 13% carcinosarcoma. 19 pts were White, 8 African American, 2 identified as Asian, 1 unknown. In the MMR deficient patients, event-free probability was 11.9 months. Grade 3 or 4 treatment related adverse events occurred in 50% patients. Conclusion(s): To our knowledge, this trial represents the first use of a non-chemotherapybased triplet therapy for recurrent endometrial cancer. The combination of rucaparib, bevacizumab, and atezolizumab may safely be used to treat recurrent/persistent endometrial cancer. This combination demonstrates clinically meaningful improvement in response, with acceptable toxicity. Enhanced response to therapy was seen in MMR deficient subjects.

Bradshaw, A. and T. Sathyapalan (2022). "A clinical trial to see if LPRI-424 is safe and works for Polycystic Ovary Syndrome compared to a placebo for 9 months." ISRCTN registry.
	Plain English Summary Background and study aims The test medicine (LPRI-424) is being given to women with polycystic ovary syndrome (PCOS) to see if there is a change in hair growth when given for 9 months. This is being tested against a placebo and the hair growth is being measured by a tool called the Adapted Modified Ferriman-Gallwey (mFG) score. This score is used by Doctors to see how much hair growth there is for those suffering with polycystic ovary syndrome. Who can participate? Women aged 14 to 40 years diagnosed with PCOS. What does the study involve? Not provided at time of registration What are the possible benefits and risks of participating? Benefits: Improvement of PCOS symptoms in particular of hirsutism. Information learned from the trial may help other patients with hirsutism in the future. Risks: The main burden for subjects would be the E-Diary completion each day. The burden is minimised by taking less than 3 minutes to complete and the subjects being compensated for their time/compliance with the E-Diary. The amount of compensation will be given within the patient information sheet. Subjects will not be allowed any permanent hair removal during the trial, they can only use shaving as a method of hair removal. If the subject chooses to shave areas of their bodies, they must do so 15 days prior to the mFG score being tested to ensure the same standardised assessment of hair growth is done. This burden will be minimised by providing compensation to those patients who comply and complete the trial. Other risks and burdens include blood withdrawals, where the subject may get injection-site pain/discomfort. To mitigate this risk only a trained, experienced and delegated member of the study site team will perform blood withdrawals. The subjects will also have gynaecological examinations and intravaginal ultrasounds, this is an intrusive examination and the experience will be minimised by a trained and experienced member of the site team performing the assessments. Where is the study run from? Chemo Research S.L. (Spain) When is the study starting and how long is it expected to run for? September 2020 to November 2023 Who is funding the study? Chemo Research S.L. (Spain) Who is the main contact? Dr Thozhukat Sathyapalan, thozhukat.sathyapalan@hyms.ac.uk Study website

Braga, A., et al. (2022). "Urethral bulking agents for the treatment of recurrent stress urinary incontinence: A systematic review and meta-analysis." Maturitas 163: 28-37.
	Recurrent stress urinary incontinence (rSUI) represents a major challenge for most clinicians as there is little evidence in the literature on the best option after sling failure. The objective of this study is to summarise the findings on the use of urethral bulking agents (UBAs) in the management of rSUI after the failure of a mid-urethral sling (MUSs). We performed a systematic review and meta-analysis, according to PRISMA 2020 guidelines, and selected eleven publications for inclusion in the analysis. We found that the overall cure and improvement rate ranged from 64% to 85% in the included studies, with a pooled value of 75%, compared with pooled failure and re-operation rates of 32% (95% CI: 22%-43%) and 25% (95% CI: 17%-34%), respectively. The I2 test indicated significant statistical heterogeneity among the studies in relation to all the outcome measures; however, no risk of publication bias was found. To explore this heterogeneity in more depth, we performed a sub-group analysis of the two most commonly used bulking agents (Bulkamid and Macroplastique). The pooled values of the cure and improvement rate were 84% (95% CI: 77.0%-90.0%) and 80% (95% CI: 74.0%-85.0%) for Macroplastique and Bulkamid, respectively. We did not find significant heterogeneity or significant differences in the outcome measures in either group. For the first time in literature, our study provides an insight into the use of UBAs after failed MUSs. Although the results seem very promising, future studies with shared protocols are needed in order to recommend the use of UBAs in the treatment of recurrent cases.Copyright © 2022

Branco-Silva, M., et al. (2022). "Consolidation chemotherapy in postmolar low-risk gestational trophoblastic neoplasia: A systematic review protocol." BMJ Open 12(2): e059484.
	Introduction Current evidence remains insufficient to strongly demonstrate the benefits of consolidation chemotherapy to all women with low-risk gestational trophoblastic neoplasia (GTN). This protocol outlines a systematic review to investigate whether consolidation chemotherapy is necessary for all patients with postmolar low-risk GTN after human chorionic gonadotropin normalisation with first-line single-agent chemotherapy. Methods and analysis A search string will be used to search the PubMed (MEDLINE), EMBASE, Web of Sciences, Scopus, LILACS and Cochrane Central Register of Controlled Trials databases. Articles will be screened at the title and abstract level, and then at the full article level by two independent reviewers using inclusion/exclusion criteria. Randomised and non-randomised study designs will be included, while case studies, commentaries, editorials, review articles, animal studies, basic science studies and cross-sectional studies, as well as studies not reporting relapse/recurrence rates and/or whether consolidation chemotherapy was delivered will be excluded. There will be no restrictions on date of publication, geographical location, study setting, or language of publication. The primary outcome is rate of recurrence/relapse. The assessments of randomised controlled trials will be performed using the risk of bias tool from the Cochrane Collaboration. Non-randomised studies will be assessed using the Newcastle-Ottawa scale. The quality of evidence will be assessed using the Grading quality of evidence and strength of recommendations (Grades of Recommendations, Assessment, Development and Evaluation) guidelines. Ethics and dissemination No formal ethical approval is required as all data collected will be secondary data and analysed anonymously. Results will be disseminated through a peer-reviewed publication and at scientific events. PROSPERO registration number CRD42020164822.Copyright ©

Brand, S. R., et al. (2021). "A Randomized Phase 2 Study of VT-1161 for the Treatment of Acute Vulvovaginal Candidiasis." Clinical Infectious Diseases 73(7): e1518‐e1524.
	BACKGROUND: Acute vulvovaginal candidiasis (VVC) is common among women, but current azole antifungal treatments are often associated with safety and resistance issues. VT‐1161 (oteseconazole) is an oral agent with increased selectivity for fungal CYP51. In this phase 2 clinical study, we evaluated the efficacy and safety of VT‐1161 vs fluconazole in participants with moderate to severe acute VVC. METHODS: Participants presenting with an acute episode of VVC (n = 55) were randomized to receive VT‐1161 300 mg once daily (q.d.) for 3 days, 600 mg q.d. for 3 days, or 600 mg twice daily (b.i.d.) for 3 days or to receive a single dose of fluconazole 150 mg (FDA‐approved dose to treat acute VVC). Participants were followed for 6 months. The primary outcome was the proportion of participants with therapeutic (clinical and mycological) cure at day 28. RESULTS: A larger proportion of participants in the per‐protocol population experienced therapeutic cure in the VT‐1161 300 mg q.d. (75.0%), VT‐1161 600 mg q.d. (85.7%), and VT‐1161 600 mg b.i.d. (78.6%) groups vs the fluconazole group (62.5%); differences were not statistically significant. At 3 and 6 months, no participants in the VT‐1161 groups vs 28.5% and 46.1% in the fluconazole group, respectively, had evidence of mycological recurrence. No serious adverse events or treatment‐emergent adverse events leading to discontinuation were reported. CONCLUSIONS: The majority of participants across all treatment groups achieved therapeutic cure at day 28. VT‐1161 was well tolerated at all dose levels through 6 months of follow‐up. CLINICAL TRIALS REGISTRATION: NCT01891331.

Brandon, G., et al. (2021). "Efficacy of Neuromodulation in Treating Chronic Pelvic Pain: A Systematic Review."
	
Brandt, C. and E. C. J. van Vuuren (2022). "Postoperative Physiotherapy in Women Undergoing Pelvic Floor Reconstructive Surgery: A Randomized Controlled Clinical Trial." Physiotherapy Canada. Physiotherapie Canada 74(2): 126-138.
	Purpose: Postoperative physiotherapy in conjunction with pelvic organ prolapse (POP) surgery is still under-investigated and controversial. In this randomized controlled trial, pelvic floor muscle training (PFMT) and abdominal training were compared with a control condition (standard in-hospital treatment). Method: Eighty-one women were randomized to one of three groups. The Prolapse Quality of Life questionnaire, two-dimensional ultrasound, Pelvic Organ Prolapse Quantification System scale, the PERFECT (power, endurance, repetitions, fast contractions, every contraction timed) scheme, electromyography, Sahrmann scale, and pressure biofeedback unit (PBU) were used to measure quality of life (QOL), POP, and pelvic floor and abdominal muscle function. A mixed-model analysis of variance and the Kruskal-Wallis test was used for analysis. Results: Beneficial effects (p < 0.05) were found for the PFMT group - increased power, number of fast contractions, amount of movement, endurance, and Sahrmann and PBU measures - compared with the control group. Abdominal training led to a significant (p < 0.05) increase in bulging and discomfort, number of pelvic floor muscle contractions, and Sahrmann and PBU measures compared with the control condition; both groups showed significantly increased urinary frequency (p < 0.05). Conclusions: Postoperative physiotherapy did not have a beneficial effect on QOL or POP symptoms. PFMT and abdominal training had beneficial effects on pelvic floor muscle function and abdominal muscle measures. Additional abdominal training led to increased symptoms.

Brasoveanu, S., et al. (2023). "Laparoscopic Pectopexy versus Vaginal Sacrospinous Ligament Fixation in the Treatment of Apical Prolapse." Life (Basel, Switzerland) 13(10).
	Objectives: To compare the follow-up results of a sacrospinous ligament fixation (SSLF) technique for laparoscopic bilateral fixation of the vagina to the iliopectineal ligament via a PVDF-mesh (laparoscopic pectopexy technique, LP) in terms of cure rate and postoperative complications rate.; Material and Methods: This prospective study included 160 patients diagnosed with pelvic organ prolapse stage II-IV according to the POP-Q system. Eighty-two patients (51.25%) underwent vaginal sacrospinous ligament fixation and seventy-eight patients (48.75%) underwent the laparoscopic pectopexy procedure.; Results: The cure rate was high in both groups, 95.12% of the patients (78 out of 82) in the SSLF group and 93.59% of the patients (73 out of 78) in the LP group were cured post surgery, leading to an overall cure rate of 151 out of 160 patients. Pelvic pain was present in 5.00% of all patients, but was notably more frequent in the SSLF group (7, 8.54%) than in the LP group (1, 1.28%). Dyspareunia occurred in 4.37% of all patients, slightly more frequently in the SSLF group (6, 7.32%) than the LP group (1, 1.28%), but without significant difference.; Conclusions: The laparoscopic pectopexy procedure has comparably positive follow-up results with the conventional sacrospinous ligament fixation procedure. Both SSLF and LP are effective in the treatment of pelvic organ prolapse, with favorable anatomical and subjective results, a high cure rate and low rates of serious postoperative complications.

Brasoveanu, S., et al. (2023). "Evaluating Patient Preferences and Clinical Outcomes in Stress Urinary Incontinence Treatment: A Short-Term Follow-Up Study of the Transobturator Tape Procedure and Pubourethral Ligament Plication (a Minimally Invasive Technique)." Journal of Personalized Medicine 14(1).
	Objective: This study aims to provide an in-depth analysis of patient preferences and clinical outcomes associated with two surgical techniques for treating stress urinary incontinence (SUI): the transobturator suburethral sling (TOT) procedure and the pubourethral ligament plication (PUL) procedure. We evaluated the rates of postoperative complications, the duration of each procedure, hemoglobin loss, and days of hospitalization.; Materials and Methods: This prospective study included 80 patients who underwent surgery for SUI: 40 patients for the TOT procedure and 40 patients for the PUL procedure. Clinical data on patient characteristics, treatment efficacy, and post-surgical outcomes were analyzed to assess patient preferences and real-world clinical effectiveness.; Results: Regarding patient preferences, those who underwent TOT surgery were more likely to be older, had a higher average number of pregnancies, and were more often postmenopausal, in contrast to those who underwent PUL surgery ( p < 0.001 for each comparison). TOT patients had a hospital stay on average of 1.02 days, while PUL patients benefited from ambulatory stays only. In addition, the TOT group had a significantly longer average operating time (16.80 min) compared to the PUL group (9.90 min, p < 0.001). The study revealed notable outcomes in both groups, with high cure rates for both TOT (N 1 = 33, 82.5%) and PUL (N 2 = 28, 70%) procedures. Specifically, 76.25% of the patients (61 out of 80) were cured after the procedures. Chronic pelvic pain was present in 3.75% of all patients and was notably only observed in the TOT group, with 3 (7.5%) cases being noted. Similarly, vaginal erosion was experienced by 5% of all patients, with 10% of patients in the TOT group and none in the PUL group being affected. Dyspareunia occurred in 2.5% of all patients, with there being two (5%) cases in the TOT group and none in the PUL group.; Conclusions: This study highlights that while the PUL procedure achieves cure rates comparable to TOT, it offers a less invasive option with shorter operating times and no hospitalization required. These findings suggest that PUL could be a viable alternative for stress urinary incontinence (SUI) treatment, especially in contexts where avoiding mesh use is preferred. This adds significant value to patient-centered care in SUI management, offering tailored treatment options based on patient characteristics, preferences, and risk profiles.

Brassil, K. J., et al. (2023). "Trial in progress: Comprehensive outcomes for after cancer health (COACH), a randomized trial assessing health outcomes following primary cancer therapy." Cancer Research 83(7 Supplement).
	Purpose: This study evaluates feasibility and acceptability of a digital health coaching intervention for individuals who are within one year of completing primary cancer treatment of any modality, as well as its effect on health self-efficacy. Secondary endpoints evaluate trends in patient-reported outcomes (PRO), including financial toxicity, for which the Economic StraiN and Resilience in Cancer (ENRICh) tool is being validated. Additional endpoints explore associations between patientreported symptoms, wearable, biomarker, and clinical data. This study seeks to fill a critical knowledge gap as to how health behavioral changes prompted by health coaching may modulate symptoms and physical/psychosocial well-being through the longitudinal tracking of patient reported, clinical, and bioinformatic data. Method(s): This randomized, wait-list control trial is being conducted at geographically diverse National Cancer Institute-designated cancer centers. Per site enrollment is <150 participants, aged 18 and older, following completion of primary treatment for breast, ovarian, endometrial, lung, or gastric cancer or population specific (eg, >=65 years) cohorts. A 6-month coaching intervention utilizing phone calls coupled with supplemental digital content via text, email, or web-based application is delivered during months 1 through 6 (intervention) or months 7 through 12 (wait-list control). PROMIS and other validated questionnaires and activity data are collected over 12 months. Gut microbiome specimens and the Diet History Questionnaire (DHQ) III are collected at enrollment and 6 months. Feasibility (retention rate >=70%) and acceptability (<=20% scoring "not at all helpful"), are assessed with descriptive statistics. Summary Data: To date, 47 individuals have been enrolled at 3 study sites, Nebraska Medicine (36), Dana-Farber Cancer Institute (10), and The Ohio State University James Cancer Center (1). This includes 1 male and 46 female participants, with an average age of 63.62 (R 33-75), of whom 44 identify as White and 3 as Black or African American, and 47 identify as non-Hispanic. Among participants, 35 have a history of breast, 10 ovarian, 1 endometrial, and 1 gastric cancer. Two additional sites are planned to begin enrollment in 2023, one of which will primarily enroll participants identifying as Black and/or Hispanic. Conclusion(s): Enrollment is anticipated to complete by December 2023 with site-specific and composite results reported by December 2024. Novel outcomes related to the use of digital health coaching in the context of survivorship, as well as robust data assessing clinical, microbiome, dietary, patient-reported, and wearable data is expected to enhance existing evidence regarding outcomes in patients on both active surveillance and maintenance therapies for diverse tumor types.

Brau-Figueroa, H., et al. (2022). "Effectiveness of Concomitant Chemoradiotherapy with Gemcitabine in Locally Advanced Cervical Cancer Patients with Comorbidities." Cancer research and treatment 54(2): 554-562.
	Purpose: The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy with cisplatin (CDDP) followed by brachytherapy. The presence of comorbidities are risk factors for nephrotoxicity and are associated with lower survival. Gemcitabine is a radiosensitizing drug that has shown efficacy and safety in this context. The effectiveness of concomitant chemoradiotherapy with gemcitabine was evaluated versus cisplatin in LACC patients with comorbidities and preserved renal function.; Materials and Methods: An observational, longitudinal and paired study was carried out that included patients treated between February 2003 and December 2015. The primary objectives were to evaluate response rates, progression-free survival, and overall survival; the secondary objectives were to evaluate toxicity and renal function.; Results: Sixty-three patients treated with gemcitabine at 300 mg/m2 weekly and 126 patients treated with CDDP 40 mg/m2 weekly were included. There were no significant differences in response rates and survival rates. Treatment with cisplatin presented a higher frequency of hematological toxicities, while gemcitabine presented a higher frequency of gastrointestinal toxicities. A decrease in glomerular filtration rate (GFR; baseline vs. 1-year post-treatment) was observed in the cisplatin group (p=0.002), while not in the gemcitabine group (p=0.667). In a multivariate analysis, it is observed that only CDDP correlates with the decrease in GFR (hazard ratio, 2.42; p=0.012).; Conclusion: In LACC patients with comorbidities, gemcitabine and CDDP show the same efficacy, with different toxicity profiles. Treatment with cisplatin is associated with a significant decrease in GFR during follow-up, compared to treatment with gemcitabine that does not decrease it.

Brawijaya University, o. (2022). Hypogastric Plexus Block and Ganglion Impar Block for Cervical and Endometrial Cancer Pain Management.
	No Results Available Procedure: Superior Hypogastric Plexus Block|Procedure: Ganglion Impar Block Numerical rating scale (NRS)|Oswestry Disability Index (ODI)|Morphine equivalent daily dose (MEDD)|Adverse effect Female Not Applicable 36 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Supportive Care UB_WWN01 April 30, 2023

Brennen, R., et al. (2021). "Group-based pelvic floor muscle training for all women during pregnancy is more cost-effective than post-natal training for women with urinary incontinence: Cost-effectiveness analysis of a systematic review." Neurourology and Urodynamics 40(SUPPL 2): S86-S88.
	HYPOTHESIS / AIMS OF STUDY Despite evidence for pelvic floor muscle training (PFMT) to effectively prevent or treat postnatal urinary or faecal incontinence, (1, 2) there have been no studies evaluating the cost-effectiveness of different models-of-care to deliver PFMT in pregnancy or the postnatal period. Such an evaluation is needed to provide health services with relevant data to inform service planning. We therefore undertook this review to determine the costs and cost-effectiveness of different models-of-care delivered to provide PFMT in pregnancy or the postnatal period. STUDY DESIGN, MATERIALS AND METHODS Studies included in a recent Cochrane Systematic Review (1) on supervised PFMT during pregnancy or in the postnatal period for preventing or treating postnatal urinary incontinence and / or postnatal faecal incontinence were grouped according to model-of care and meta-analysis performed on these groupings. For models-of-care that showed a statistically significant impact on preventing or curing urinary and / or faecal incontinence, a cost-effectiveness analysis was undertaken. A base case for each model-of-care was generated based on the median number of sessions and duration of sessions and staffing levels of the reported interventions. Costs for each model-of-care were based on publicly available data on costs of consumables, room hire, staffing, and median wage of women of childbearing age. Sensitivity analysis was conducted for variables of the number of women attending group sessions, population employment levels and staffing hourly rates. RESULTS Seventeen studies were included for meta-analysis. Three models-of-care were clinically effective: individually-supervised PFMT during pregnancy to prevent urinary incontinence (Model 1), group-based PFMT during pregnancy to prevent or treat urinary incontinence (Model 2) and individually- supervised postnatal PFMT to treat urinary incontinence and prevent or treat faecal incontinence (Model 3). The health service costs per urinary incontinence case prevented or cured were $768 for Model 1, and $1,970 for Model 3. Model 2 generated a cost saving of $14 if there were 8 participants per session, with greater savings if more participants attend. The health service cost per faecal incontinence case prevented or cured was $2,784 (Model 3). Table 1 shows the costs for the different individually-supervised PFMT modelsof- care, while Figure 1 shows the cost per person according to number of attendees for group-based PFMT during pregnancy to prevent or treat urinary incontinence. INTERPRETATION OF RESULTS This was the first study to identify comparative cost-effectiveness of different modeal of care for preventing or treating postnatal incontinence. Individual PFMT delivery during pregnancy to prevent urinary incontinence was the most cost-effective model for overall costs. Group-based PFMT during pregnancy to prevent urinary incontinence was the most cost-effective model from a health service perspective, depending on the number of women attending the group-based intervention and the out-of-pocket costs charged. It is important to note that patients included in these studies did not have urinary incontinence at the start of treatment. For existing urinary incontinence, individual PFMT during pregnancy did not have a statistically significant clinical effect, although there was a trend towards positive outcomes in these analyses. One of the included studies provided minimal details about their intervention other than that there were only 1-2 treatment sessions. As supervision has been identified as a significant factor in achieving outcomes, (3) this may account for the lack of statistically significant clinical effect in both this individual study and the meta-analyses of this model. Most of the studies of postnatal PFMT focused on individual PFMT for treatment or for mixed prevention and treatment of urinary incontinence. Due to the lack of significant findings in the few studies that assessed group-based or mixed group and individual models, we did not analyse thes models for cost-effectiveness. Individual postnatal PFMT to treat urinary incontinence was both clinically significant and cost-effective. Based on our meta-analysis and cost-effectiveness analysis results: It is recommended that all continent pregnant women are provided with the opportunity to participate in urinary incontinence prevention services during pregnancy. It is more efficient for health service providers to provide group-based prevention services during pregnancy to continent pregnant women than provide individual treatment services to incontinent women postnatally if at least 4 women can attend the group sessions. Group-based prevention is preferable to individual prevention if: * At least 5 women can attend the group sessions and the service charges $10 per session * At least 8 women can attend the group sessions and the service charges $5 per session * At least 13 women can attend the group sessions and there is no charge per session We are unable to make any recommendations regarding early in-hospital postnatal PFMT or education sessions due to the lack of studies specific to the early postnatal period. We are unable to make a clear recommendation regarding whether it is better to provide prevention during pregnancy or treatment postnatally. While it is more efficient for health service providers to provide prevention services during pregnancy to continent pregnant women than to provide treatment services to women incontinent of urine postnatally, postnatal treatment has the additional benefit of preventing or treating faecal incontinence. If a health service is investing resources in prevention of urinary incontinence amongst pregnant women: * If at least 5 women can attend group PFMT, it is recommended that continent women are provided with the opportunity to participate in group PFMT during pregnancy for prevention of urinary incontinence. * If only 4 or fewer women can attend group PFMT, it is recommended that continent women are provided with the opportunity to participate in individual PFMT during pregnancy for prevention of urinary incontinence. CONCLUDING MESSAGE PFMT during pregnancy for prevention of postnatal urinary incontinence is a clinically effective and cost-effective treatment, with cost-effectiveness of group-based compared to individually supervised PFMT being dependent on the number of women who can attend a group and on whether the health service charges a co-payment for the service. Individually supervised PFMT for treatment of postnatal urinary incontinence is a clinically effective and cost-effective treatment that also provides effective prevention and treatment of faecal incontinence.

Brennen, R., et al. (2021). "Group-based pelvic floor muscle training for all women during pregnancy is more cost-effective than postnatal training for women with urinary incontinence: cost-effectiveness analysis of a systematic review." Journal of Physiotherapy 67(2): 105-114.
	QUESTION: What is the most cost-effective way of providing pelvic floor muscle training (PFMT) to prevent or treat postpartum incontinence? DESIGN: Meta-analysis and cost-effectiveness analysis of models of care included in a recent Cochrane systematic review. PARTICIPANTS: Pregnant and postnatal women. INTERVENTION: Supervised PFMT for preventing or treating urinary and/or faecal incontinence. OUTCOME MEASURES: Postpartum urinary or faecal incontinence. ANALYSIS: We examined the comparative incremental cost effectiveness of different approaches to successfully prevent or cure one case of incontinence. Costs were valued in Australian dollars using publicly available market rates and enterprise agreements as of 2019. Comparisons involving group-based treatment approaches were subject to sensitivity analyses where the numbers of patients attending each group were varied to identify thresholds where recommendations change. RESULT(S): Seventeen trials were included for meta-analysis. Three models of care were clinically effective: individually supervised PFMT during pregnancy to prevent urinary incontinence (Model 1), group-based PFMT during pregnancy to prevent or treat urinary incontinence (Model 2) and individually supervised postnatal PFMT to treat urinary incontinence and prevent or treat faecal incontinence (Model 3). The health service costs per urinary incontinence case prevented or cured were $768 for Model 1, and $1,970 for Model 3. However, Model 2 generated a cost saving of $14 if there were eight participants per session, with greater savings if more participants attend. The health service cost per faecal incontinence case prevented or cured was $2,784 (Model 3). CONCLUSION(S): Providing group-based PFMT for all women during pregnancy is likely more efficient than individual PFMT for incontinent women postnatally; however, providing PFMT for postnatal women with urinary incontinence should not be discounted because of the added known benefit for preventing and treating faecal incontinence.Copyright © 2021 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Brennen, R., et al. (2020). "The Effect of Pelvic Floor Muscle Interventions on Pelvic Floor Dysfunction After Gynecological Cancer Treatment: A Systematic Review." Physical Therapy 100(8): 1357-1371.
	Objective: The aim of this systematic review was to identify, evaluate, and synthesize the evidence from studies that have investigated the effect of nonsurgical, nonpharmacological, pelvic floor muscle interventions on any type of pelvic floor dysfunction or health-related quality of life in patients after any type of treatment for gynecological cancer.; Methods: Six electronic databases (Cochrane Library 2018, CINAHL 1982-2018, MEDLINE 1950-2018, EMBASE 1980-2018, PsycINFO 1806-2018, and EMCARE 1995-2018) were systematically searched in June 2018. Reference lists of identified articles were hand searched. Randomized controlled trials (RCTs), cohort studies, and case series were included if they investigated the effects of conservative treatments, including pelvic floor muscle training or dilator training, on bladder, bowel, or sexual function in patients who had received treatment for gynecological cancer. Risk of bias was assessed using the Physiotherapy Evidence Database scale for RCTs and the Newcastle-Ottawa scale for cohort studies.; Results: Five RCTs and 2 retrospective cohort studies were included (n = 886). The results provided moderate-level evidence that pelvic floor muscle training with counseling and yoga or core exercises were beneficial for sexual function (standardized mean difference = -0.96, 95% CI = -1.22 to -0.70, I2 = 0%) and health-related quality of life (standardized mean difference = 0.63, 95% CI = 0.38 to 0.88, I2 = 0%) in survivors of cervical cancer and very low-level evidence that dilator therapy reduced vaginal complications in survivors of cervical and uterine cancer (odds ratio = 0.37, 95% CI = 0.17 to 0.80, I2 = 54%). There were insufficient data for meta-analysis of bladder or bowel function.; Conclusion: Conservative pelvic floor muscle interventions may be beneficial for improving sexual function and health-related quality of life in survivors of gynecological cancer. Given the levels of evidence reported in this review, further high-quality studies are needed, especially to investigate effects on bladder and bowel function.; Impact: This review provides moderate-level evidence for the role of pelvic floor rehabilitation to improve health outcomes in the gynecological cancer survivorship journey. Clinicians and health service providers should consider how to provide cancer survivors the opportunity to participate in supervised pelvic floor rehabilitation programs. (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Breschi, L., et al. (2023). "Development of an atlas-based segmentation tool for gynecological Interventional Radiation Therapy." Radiotherapy and Oncology 182(Supplement 1): S1965-S1966.
	Purpose or Objective Radiotherapy treatment involves several steps requiring accuracy and precision, performed by different professional figures. Physicians are responsible for the contouring activity, where they identify the tumor as the CTV structure and all the organs at risk (OARs). Despite this practice is regularized by international guidelines shared within the medical community, the inter- and intra-operator variability represents a limit to achieving the optimal results in terms of treatment success. This approach exploits the availability of a certain number of CT series, contoured by an expert physician. For interventional radiation therapy (IRT, brachytherapy) the contouring step is relevant and even more challenging than external beam radiotherapy (EBRT), because of the presence of applicators. The use of atlas-based segmentation in IRT, already tested for EBRT, may improve the treatment delivery in terms of time and repeatability. Materials and Methods CT images acquired on a Discovery CT590 RT CT scanner (GE Healthcare) were collected for 30 patients with cervical cancer and IRT prescription. They were reconstructed using a matrix of 512x512 and thickness of 0.62 mm. Bladder, bowel bag and rectum structures were defined as OARs and manually generated by an expert radiation oncologist on a dedicated treatment planning system (TPS Oncentra Masterplan v 4.6, Elekta). All the enrolled patients received intracavitary highdose- rate IRT with vaginal applicators of 3 cm diameter. MIM Maestro v.7.1.2 (MIM Software), installed on a workstation with Intel Core i7-7700 CPU and 16 GB RAM, was employed to build a CT atlas for female pelvis. A specific workflow for auto-segmentation of OARs for cervical cancer BT was created. Two algorithms for final contours creation, Majority Vote (MV) and STAPLE (Warfield et al. 2004) were compared, with two kinds of atlases: the first one masking the applicator in order to minimize its effect and the second one without masking the applicator. To evaluate the atlas performances, the Dice Coefficient (DC) and Mean Distance Agreement (MDA) were computed. Results The workflow gave the best results for DC and MDA in the case of the bladder (DC = 0.79 and MDA = 3.06 mm) corresponding to good reproducibility. Lower values were observed (DC = 0.61(0.54) and MDA = 3.54(6.77) mm) for rectum and bowel bag, respectively. The comparison between algorithms showed higher performances with STAPLE than MV (p < 0.05). No relevant differences were stated between atlases. Fig.1Bladder contour obtained with MIM. Conclusion This study analyzed performances of an atlas-based segmentation method with MIM MAESTRO. The best proposal of bowel bag, rectum and bladder contours in HDR interventional radiation therapy was obtained using the STAPLE algorithm. No difference was found between the two atlases, thus implying that masking the applicator is not necessary. Future steps will involve the increase of the number of atlas' subjects and the comparison with neural networks performances. [Figure presented]Copyright © 2023 Elsevier B.V.

Breuer, M., et al. (2022). "Warm and humidified insufflation gas during gynecologic laparoscopic surgery reduces postoperative pain in predisposed patients-a randomized, controlled multi-arm trial." Surgical Endoscopy 36(6): 4154-4170.
	Background: Postoperative pain remains a common problem in gynecologic laparoscopy, especially in head zone-related regions, triggered by intra-abdominal pressure during capnoperitoneum. Humidified and prewarmed insufflation gas may ameliorate pain and be beneficial.; Methods: This prospective randomized controlled parallel group multi-arm single-center study investigated the effects of temperature and humidity of insufflation gas on postoperative pain during gynecologic laparoscopy with a duration ≥ 60 min. Female participants (18-70 years) were blinded and randomly assigned-computer generated-to either insufflation with dry cold CO 2 with forced air warming blanket ("AIR"), humidified warm gas without forced air warming blanket ("HUMI"), or humidified warm gas with forced air warming blanket ("HUMI +"). We hypothesized that using humidified warm gas resulted in lower pain scores and less analgesic consumption. The primary endpoint postoperative pain was assessed for different pain localizations every 12 h during 7 days after surgery. Secondary endpoints were demand for painkillers and epidural anesthetics, length of stay in recovery room, and hospital stay. (Registration: ClinicalTrials.gov NCT02781194-completed).; Results: 150 participants were randomized. Compared to group "AIR" (n = 48), there was significantly less pain in group "HUMI +" (n = 48) in the recovery room (- 1.068; 95% CI - 2.08 to - 0.061), as well as significantly less ibuprofen use at day two (- 0.5871 g ± 0.258; p-value = 0.0471). Other variables did not change significantly. Stratification for presence of endometriosis or non-previous abdominal surgery in patient history revealed significantly less pain in both groups "HUMI" (n = 50) and "HUMI +" versus group "AIR." Related side effects were not noted.; Conclusion: In the overall population, the use of warm, humidified insufflation gas did not yield clinically relevant effects; however, in predisposed patients with endometriosis and who could otherwise expect high pain levels, warm and humidified gas may be beneficial. (© 2021. The Author(s).)

Brieger, K. K., et al. (2022). "High Prediagnosis Inflammation-Related Risk Score Associated with Decreased Ovarian Cancer Survival." Cancer Epidemiology Biomarkers and Prevention 31(2): 443-452.
	Background: There is suggestive evidence that inflammation is (IRRS) was developed, and its association with survival was related to ovarian cancer survival. However, more research is assessed using Cox proportional hazards models in the remaining needed to identify inflammation-related factors that are associated 50% of the data. with ovarian cancer survival and to determine their combined Results: There was a statistically significant trend of increasing effects. risk of death per quartile of the IRRS [HR 1/4 1.09; 95% confidence Methods: This analysis used pooled data on 8,147 women with interval (CI), 1.03-1.14]. Women in the upper quartile of the IRRS invasive epithelial ovarian cancer from the Ovarian Cancer had a 31% higher death rate compared with the lowest quartile (95% Association Consortium. The prediagnosis inflammation-related CI, 1.11-1.54). exposures of interest included alcohol use; aspirin use; other Conclusion(s): A higher prediagnosis IRRS was associated with an nonsteroidal anti-inflammatory drug use; body mass index; increased mortality risk after an ovarian cancer diagnosis. Further environmental tobacco smoke exposure; history of pelvic inflaminvestigation is warranted to evaluate whether postdiagnosis expomatory disease, polycystic ovarian syndrome, and endometriosis; sures are also associated with survival. menopausal hormone therapy use; physical inactivity; smoking Impact: Given that pre- and postdiagnosis exposures are often status; and talc use. Using Cox proportional hazards models, the correlated and many are modifiable, our study results can ultimately relationship between each exposure and survival was assessed in motivate the development of behavioral recommendations to 50% of the data. A weighted inflammation-related risk score enhance survival among patients with ovarian cancer.Copyright © 2022 American Association for Cancer Research

Brigham and W. s. Hospital (2024). Study on Allopregnanolone and Depression in Women Across the Menopause Transition.
	No Results Available Dietary Supplement: pregnenolone|Other: placebo Within-person change in score on the Ruminative Responses Scale Female Not Applicable 80 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Other 2024P000113 August 31, 2027

Brigham, et al. (2024). The Anabolic Effect of Testosterone on Pelvic Floor Muscles.
	No Results Available Drug: Testosterone cypionate|Drug: Placebo Change in pelvic floor muscle volume|Change in abdominal leak point pressure|Change in urine flow rate|Change in bladder pressure|Change in post void residual urine volume|Change in urinary symptoms|Change in quality of life Female Phase 2 30 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 2023P002632|R01DK136904 July 2026

Bright, C. and Inc (2024). Safety and Efficacy of YB-1113 in Treatment of POI.
	No Results Available Drug: YB-1113 Incidence of treatment-emergent adverse events (AE)|Blood anti-Müllerian hormone (AMH) level|Follicle-stimulating hormone (FSH) and estradiol (E2) levels|Antral follicle counts (AFC) Female Phase 1 6 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment YB1113-POI August 30, 2025

Bright, K., et al. (2020). "Effectiveness of psychological interventions on mental health, quality of life and relationship satisfaction for individuals and/or couples undergoing fertility treatment: a systematic review and meta-analysis protocol." BMJ Open 10(7): e036030.
	INTRODUCTION: Infertility is a global public health problem affecting men, women and couples worldwide. The medical implications of infertility are often of primary focus in healthcare settings, but the experience of infertility also has a considerable social, emotional and psychological impact. Interventions aimed at alleviating psychological symptoms in individual and/or couples undergoing fertility treatment requires a systematic and comprehensive review of the literature to determine the efficacy of psychological interventions. The objective of this review is to evaluate the effectiveness, feasibility and acceptability of psychological interventions for individuals and/or couples seeking fertility to treat anxiety, depression, distress, quality of life and relationship satisfaction, as well as improve pregnancy rates. METHODS AND ANALYSIS: The search strategy will involve 11 databases, including MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials (OVID), The Cumulative Index to Nursing and Allied Health Literature (CINAHL) with Full Text (EBSCO), Social Work Abstracts (EBSCO), SocINDEX with Full Text (EBSCO), Academic Search Complete (EBSCO), Family & Society Studies Worldwide (EBSCO), Family Studies Abstracts (EBSCO) and Scopus. These databases will be searched from their inception to September 2019. Independent reviewers will search peer-reviewed published studies through electronic databases and additional sources, will extract the data and assess the methodological quality. Random-effects meta-analysis will be carried out by calculating effect sizes as Cohen's d indices. Heterogeneity will be examined by the I2 and the Q statistics. ETHICS AND DISSEMINATION: The current review does not require ethics approval. The results will be disseminated through publications in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42019133757.

Bright Katherine, S., et al. (2020). "Interpersonal Psychotherapy to Reduce Psychological Distress in Perinatal Women: A Systematic Review." International Journal of Environmental Research and Public Health 17(22).
	Background: Interpersonal psychotherapy (IPT) is a psychological intervention with established efficacy in the prevention and treatment of depressive disorders. Previous systematic reviews have not evaluated the effectiveness of IPT on symptoms of stress, anxiety, depression, quality of life, relationship satisfaction/quality, social supports, and an improved psychological sense of wellbeing. There is limited information regarding moderating and mediating factors that impact the effectiveness of IPT such as the timing of the intervention or the mode of delivery of IPT intervention. The overall objective of this systematic review was to evaluate the effectiveness of IPT interventions to treat perinatal (from pregnancy up to 12 months postpartum) psychological distress.; Methods: MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials (OVID), CINAHL with Full Text (Ebsco), Social Work Abstracts (Ebsco), SocINDEX with Full Text (Ebsco), Academic Search Complete (Ebsco), Family & Society Studies Worldwide (Ebsco), Family Studies Abstracts (Ebsco), and Scopus databases were searched from inception until 31 January 2019. Two researchers independently screened articles for eligibility. Of the 685 screened articles, 43 met the inclusion criteria. The search was re-run on 11 May 2020. An additional 204 articles were screened and two met the inclusion criteria, resulting in a total of 45 studies included in this review. There were 25 Randomized Controlled Trials, 10 Quasi-experimental studies, eight Open Trials, and two Single Case Studies. All included studies were critically appraised for quality.; Results: In most studies (n = 24, 53%), the IPT intervention was delivered individually; in 17 (38%) studies IPT was delivered in a group setting and two (4%) studies delivered the intervention as a combination of group and individual IPT. Most interventions were initiated during pregnancy (n = 27, 60%), with the remaining 18 (40%) studies initiating interventions during the postpartum period.; Limitations: This review included only English-language articles and peer-reviewed literature. It excluded government reports, dissertations, conference papers, and reviews. This limited the access to grassroots or community-based recruitment and retention strategies that may have been used to target smaller or marginalized groups of perinatal women.; Conclusions: IPT is an effective intervention for the prevention and treatment of psychological distress in women during their pregnancy and postpartum period. As a treatment intervention, IPT is effective in significantly reducing symptoms of depression and anxiety as well as improving social support, relationship quality/satisfaction, and adjustment. Systematic Review Registration: PROSPERO CRD42019114292.

Brink, G. J., et al. (2022). "Response to Systemic Therapies in Ovarian Adult Granulosa Cell Tumors: A Literature Review." Cancers 14(12): 2998.
	For adult granulosa cell tumors (aGCTs), the preferred treatment modality is surgery. Chemotherapy and anti-hormonal therapy are also frequently used in patients with recurrent aGCT. We aimed to review the existing literature on the response to chemotherapy and anti-hor-monal therapy in patients with aGCT. Embase and MEDLINE were searched from inception to November 2021 for eligible studies. Objective response rate (ORR) was calculated as the total number of cases with a complete response (CR) or a partial response (PR). Disease control rate (DCR) was defined as the sum of cases with CR, PR or stable disease (SD). A total of 10 studies were included that reported on chemotherapy and 13 studies were included that reported on anti-hormonal ther-apy. The response rates of the 56 chemotherapy regimens that could be evaluated resulted in an ORR of 30% and DCR of 58%. For anti-hormonal therapy, the results of 73 regimens led to an ORR of 11% and a DCR of 66%. Evidence on systemic therapy in aGCT only is limited. For both chemotherapy and anti-hormonal therapy, the ORR is limited, but the response is considerably higher when patients achieving SD are included. New approaches are needed to provide more evidence and standardize treatment in aGCT.Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Broekman, K. E., et al. (2021). "Clinical benefit of systemic therapies for recurrent ovarian cancer-ESMO-MCBS scores." ESMO Open 6(4): 100229.
	Background: Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS).; Materials and Methods: A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS.; Results: A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making.; Conclusion: Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse.; Competing Interests: Disclosure MJ serves on the advisory board of AstraZeneca and Merck, with funding to institution. The remaining authors have declared no conflicts of interest. (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Broi Michele Gomes, D., et al. (2021). "Screening of Variants in the Transcript Profile of Eutopic Endometrium from Infertile Women with Endometriosis during the Implantation Window." Rev. bras. ginecol. obstet 43(6): 457-466.
	Objective Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. Methods Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease's context. Results None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. Conclusion Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial

Brown, N. (2021). "Cost-effectiveness of Interventional Radiology techniques in Australia: Towards sustainable, more affordable healthcare." Journal of Medical Imaging and Radiation Oncology 65(SUPPL 1): 82.
	Purpose: Interventional Radiology is an evolving clinical specialty that can improve patient outcomes, reduce treatment costs and strengthen the role of radiology within modern healthcare. This has the potential to position RANZCR as a leader in Value-Based Healthcare as minimally-invasive, image-guided IR and INR procedures are increasingly integrated into contemporary clinical algorithms. But to fulfil this potential and expand interventional radiology practise, high quality, comprehensive cost-effectiveness analyses will be required to prove the value of IR and INR to clinicians, managers, policy-makers and patients. This research develops cost-effectiveness models that can be applied across the spectrum of interventional radiology practise to determine the potential value of IR procedures to the Australian healthcare system. Methods and Materials: Markov models were developed to evaluate Quality-Adjusted Life Years (QALYs), lifetime cost burdens and incremental cost-effectiveness ratios (ICERs) for two common clinical presentations that can be treated with interventional radiology procedures or surgical alternatives. The initial comparisons were between percutaneous ablation of renal masses, partial nephrectomy and radical nephrectomy, and uterine fibroid embolization, myomectomy and hysterectomy. Data and assumptions on efficacy, re-treatment, complications, side-effects and quality of life were determined from a review of all relevant meta-analyses within the PubMed and Embase databases. Data on costs of treatment and subsequent healthcare were sourced from Medicare, public hospital and private hospital databases. Result(s): Interventional radiology procedures for the treatment of small renal masses and uterine fibroids are highly cost-effective and can result in improved patient outcomes. When compared to surgical interventions, IR procedures can yield higher quality adjusted life year values for patients and result in significant overall cost savings. Incremental cost-effectiveness ratios vary depending on costs of treatment in public or private hospitals. Medicare data indicate that these procedures are currently under-utilised. Conclusion(s): Percutaneous ablation of small renal masses and uterine fibroid embolization constitute high-value treatment options and should be more prominent in clinical algorithms. From a public health perspective, increased uptake of these procedures could save millions of dollars from both state and federal health budgets, improve the allocation of health resources, provide justification for increased IR training programs and expand patient access to essential services. These models can be applied to other IR and INR procedures, and additional cost-effectiveness analyses are now being undertaken to develop a comprehensive account of the true value of interventional radiology.

Bruce, P., et al. (2021). "Effects of different frozen embryo transfer regimens on abnormalities of fetal weight, large for gestational age, and macrosomia: a systematic review and meta-analysis."
	
Brule, K., et al. (2023). "A 6-month Lifestyle Intervention Program Improves Quality Of Life And Motivation In Women With Obesity And Infertility." Journal of the Endocrine Society 7(Supplement 1): A861.
	Introduction Infertility is the incapacity to conceive after 12 months of regular and unprotected sexual intercourse, affecting 11 to 16% of couples. Obesity affects fertility, increases fertility treatment costs, diminishes their efficacy, predisposes to many complications during pregnancy and presents risks for the offspring. To prevent those consequences, many organizations recommend that women with obesity be assisted in adopting healthy lifestyle habits before conception and maintain them during pregnancy. Also, women with infertility and those living with obesity score lower on the quality of life (QoL) scales. Therefore, our objective was to assess the impact of a lifestyle intervention on QoL and stages of change (based on the transtheoretical model) in women with obesity and seeking fertility treatments. Methods Women 18-40 years old with infertility and obesity (body mass index (BMI) >= 30 kg/m2 or BMI >= 27 kg/m2 for those with polycystic ovary syndrome), consulting at the fertility clinic of an academic center, were enrolled and randomized to usual fertility care (control group, CG) or the intervention program (lifestyle group, LSG) alone for 6 months and then combined to usual care. The lifestyle program focused on improving physical activity and nutrition and was based on motivational communication. It involved individual follow-ups with a nutritionist and a kinesiologist at weeks 0, 3, 6 and then every 6 weeks for 18 months. Also, participants needed to attend 12 group sessions, including workshops and physical activities. QoL scores from the SF-6D and FertiQol, levels of conviction (visual analog scales on 100), and stages of change were collected at baseline and at 6 months. Proportions were compared by Pearson chi-square tests and means by Student's t tests or ANCOVA (correcting for the baseline value of the result). Results Among 127 women, 85 had available data at 6 months (CG=43, LSG=42). After 6 months, and compared to the CG, women in the LSG improved more their SF-6D (+0.029 +/- 0.076 vs -0.017 +/- 0.082, p = 0.009, p ANCOVA <0.001) and FertiQoL total score (+0.35 +/- 6.85 vs -2.70 +/- 11.80, p = 0.18, p ANCOVA = 0.02). A higher proportion of women in LSG improved their stage of change by >=2 categories compared to CG (40.0% vs 13.2%, p=0.008). They better maintained their level of conviction about the need to improve their food habits (+4.0 +/- 13.4 vs -2.7 +/- 17.7, p ANCOVA=0.02) or their physical activity (+2.5 +/- 10.2 vs -5.1 +/- 13.8, p=0.006, p ANCOVA=0.01). Conclusion A lifestyle program targeting women with obesity and infertility significantly helped maintain or increase their QoL, levels of conviction for food habits and physical activity, and stages of change regarding lifestyle habits compared to usual fertility care. These results suggest that such lifestyle intervention can contribute to the well-being and maintenance of lifestyle changes in women with obesity who seek fertility treatments.

Brun, J. L., et al. (2022). "Management of women with abnormal uterine bleeding: Clinical practice guidelines of the French National College of Gynecologists and Obstetricians (CNGOF)." Gynecologie Obstetrique Fertilite et Senologie 50(5): 345-373.
	Objective: To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). Design(s): A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, or medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Method(s): The last guidelines from the College national des gynecologues et obstetriciens francais (CNGOF) on the management of women with AUB was published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescent; idiopathic AUB; endometrial hyperplasia and polyps; fibroids type 0 to 2; fibroids type 3 and more; adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE methodology. Result(s): The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 present a strong agreement and 17 a weak agreement. Fourteen questions did not find any response in the literature. We preferred to abstain from recommending instead of providing expert advice. Conclusion(s): The 36 recommendations made it possible to specify the diagnostic and therapeutic strategies of various clinical situations managed by the practitioner, from the simplest to the most complex.Copyright © 2022 Elsevier Masson SAS

Brunn, E., et al. (2022). "Virtual-Reality Effects on Acute Pain during Office Hysteroscopy: A Randomized Controlled Trial." Journal of Gynecologic Surgery 38(3): 214-220.
	Objective: The goal of this research was to evaluate the use of virtual reality (VR) as a noninvasive analgesic during office hysteroscopy. Material(s) and Method(s): The participants were 50 women undergoing office-based hysteroscopy at a single clinic in Washington DC randomized to VR or standard care from May to November 2020. The VR intervention consisted of guided meditation through an Oculus Go headset. Primary outcome measurement was peak pain score during the procedure based on a 100-mm visual analogue scale score. Secondary outcomes were changes in pain scores and changes in participants' heart rates (HRs). Result(s): No significant difference emerged in pain before, during, or after the procedure between the 2 groups. The peak pain score during the procedure for the VR group was 35 (15, 60) versus 30 (9, 54) for the standard hysteroscopy group (p = 0.317). VR had no significant effect on median HR change during the procedure (-4.6 [-0.5,11.1] versus +2.8 [0.1,7.7]; p = 0.327). Largely, participants in the VR group had positive experiences: 88% reported that the music was calming and 84% reported that meditation was helpful. Conclusion(s): This study showed no statistically significant difference in pain scores or change in HR prior to, during, or after hysteroscopic procedures with VR, compared to standard care. (J GYNECOL SURG 38:214)© Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.

Bruno, V., et al. (2023). "Urological Complications in Radical Surgery for Cervical Cancer: A Comparative Meta-Analysis before and after LACC Trial." Journal of Clinical Medicine 12(17).
	Background: After the LACC trial publication in 2018, the minimally invasive approach (MIS) has severely decreased in favor of open surgery: MIS radical hysterectomy was associated with worse oncological outcomes than open surgery, but urological complications were never extensively explored in pre- versus post-LACC eras, even if they had a great impact on post-operative QoL. The purpose of this meta-analysis is to compare functional and organic urological complication rates before and after LACC trial.; Methods: An independent search of the literature was conducted 4 years before and after the LACC trial and 50 studies were included.; Results: The overall rate of urologic complications was higher in pre-LACC studies while no differences were found for organic urological complications. Conversely, the overall risk of dysfunctional urological complications showed a higher rate in the pre-LACC era. This is probably related to a sudden shift to open surgery, with potential lower thermal damage to the urinary tract autonomic nervous fibers.; Conclusions: This meta-analysis showed that the incidence of urological complications in radical cervical cancer surgery was higher before the LACC trial, potentially due to the shift to open surgery. Nevertheless, further studies are needed to shed light on the connection between minimally invasive surgery and urological damage.

Brusciano, L., et al. (2023). "EFFECTIVENESS OF PERINEAL PELVIS REHABILITATION COMBINED WITH BIOFEEDBACK AND RADIOFREQUENCY DIATHERMY (RDF) IN ANORECTAL FUNCTIONAL PAIN SYNDROMES ASSOCIATED WITH PARADOXICAL CONTRACTION OF THE LEVATOR ANI MUSCLES. A PROSPECTIVE STUDY." Arquivos de gastroenterologia 60(2): 201-207.
	•Anorectal functional pain syndrome is a very often disabling disease with a consequent significant negative impact on the patient's quality of life. Chronic proctalgia, in many patients, is secondary to the paradoxical contraction of the pelvic floor and associated with a dissynergy between the thorax-abdomen and the pelvic floor. •The use of radiofrequency diathermy with a system of static electrodes associated with biofeedback represents a valid rehabilitation option for those patients suffering from anorectal functional pain syndrome because it reduces pain and paradoxical contraction of the levator ani and improves quality of life of the patient. Background - Anorectal functional pain syndrome, also called chronic proctalgia, represents a neglected clinical entity and often confused with other syndromes such as vulvodynia or acute proctalgia. It is a very often disabling disease with a consequent significant negative impact on the patient's quality of life. Chronic proctalgia, in many patients, is secondary to the paradoxical contraction of the pelvic floor and associated with a dissynergy between the thorax-abdomen and the pelvic floor. To improve symptoms in functional anorectal pain syndromes, various rehabilitation techniques are used with the aim of promoting relaxation of the pelvic floor; however, to improve defecatory dynamics in patients with levator ani syndrome, only biofeedback has shown efficacy in a randomized study. The aim of this work is to evaluate whether a rehabilitation protocol with manometric biofeedback and radiofrequency diathermy (mt100 Fremslife emotion Tecar) reduces pain and paradoxical contraction of the levator ani and improves the quality of life in patients with anorectal pain syndromes. functional. Methods - This was a prospective study on 30 patients (20 women and 10 men) with anorectal functional pain syndrome and paradoxical contraction of the pelvic floor enrolled at the UOC of General, Minimally Invasive, Oncological and Obesity Surgery of the AOU "Luigi Vanvitelli" of Naples, Italy, from September 2021 to May 2022. All patients were evaluated with a coloproctological specialist visit followed by anorectal manometry and evaluation of altered clinical physiatric parameters (Brusciano Score). The protocol consisted of 10 rehabilitation sessions of the pelvic floor once a week and lasting approximately 45 minutes. During the sessions the patients were subjected to diathermy / radiofrequency treatment (10 minutes) with a static resistive electrode on the diaphragm, during which they were required to breathe diaphragmatically and to become aware of the perineal muscles, under the supervision of a physiotherapist; followed by application of diathermy with static capacitive (5 minutes) and resistive (10 minutes) electrode at the lumbar level. This was followed by the use of manometric biofeedback (15 minutes of tonic / phasic exercises) in order to instruct the patient on the reflex mechanism to obtain a voluntary relaxation of the external anal sphincter. The variables evaluated were Pain (VAS 0-10) and the questionnaire on the impact of colorectal and anal pathologies on the quality of life (CRAIQ-7) at the beginning, after 3 months and at the end of the treatment. Results - After 10 weeks, the rehabilitation treatment combined with diathermy and manometric biofeedback proved effective in the short term with a reduction in the scores of the Vas scale and CRAIQ-7 questionnaire and an increase in the percentage of release of the anal muscles on anorectal manometry. Conclusion - The use of radiofrequency diathermy with a system of static electrodes associated with biofeedback represents a valid rehabilitation option for those patients suffering from anorectal functional pain syndrome because it reduces pain and paradoxical contraction of the levator ani and improves quality of life of the patient.

Brussel Universitair, Z. (2021). Optimising Preconceptual Health in Subfertile PCOS Patients Using a Lifestyle Modification Program.
	No Results Available Behavioral: Lifestyle program body weight|body composition Female Not Applicable 226 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment LSPCOLMMDV October 31, 2024

Brussel Universitair, Z. (2024). Live Birth Rate After Sperm Selection Using ZyMōt Multi (850µL) Device for Intra Uterine Insemination.
	No Results Available Device: ZyMōt Multi (850µL)|Other: Density Gradient Centrifugation Cumulative live birth rate after 3 consecutive IUIs|Pregnancy rate|Miscarriages rate All Not Applicable 240 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment EC-2023-257 December 2027

Brzozowska, M. and A. Lewinski (2021). "Hormonal replacement therapy in women with a history of internal genital organ malignancy." Przeglad menopauzalny = Menopause review 20(1): 34-39.
	Sudden cessation of ovary activity as a result of bilateral oophorectomy or chemo- or radiotherapy in premenopausal women is linked with more serious consequences that bear no comparison to natural menopause - to name just a few: higher rate of mortality, higher rate of colorectal and lung cancer, circulatory system diseases, cognitive disorders, Parkinson's disease, psychological disorders, osteoporosis, and sexual disorders. The prolonged period of estrogens deficit in premenopausal age is connected with worsened quality of life. The progress in oncological care means that in many malignant diseases, also in the case of gynaecological malignancies, the percentage of survivors increases. This makes improving the quality of life more and more important. The purpose of this review is to establish, based on EBM data, the answer to whether replacement hormonal therapy, being the most effective treatment of menopause symptoms, can be recommended for women who have undergone bilateral oophorectomy because of gynaecological cancer. On the basis of collected data, derived from meta-analysis, and studies which have been published within the last 20 years, it seems that the use of the appropriate type of hormonal replacement therapy (HRT) in properly selected gynaecological cancer survivors (epithelial ovarian cancer - EOC, endometrial cancer, squamous cell carcinoma of the cervix) is safe and effective. It seems that benefits connected with better quality of life that stem from the use of appropriate HRT in gynaecological cancer survivors predominate the unfounded fear of disease recurrence in selected patients' groups.; Competing Interests: The authors report no conflict of interest. (Copyright © 2021 Termedia.)

Buchanan, A., et al. (2021). "Patient-reported outcomes of non-pharmacological interventions for endometrial cancer survivors: a systematic review." Journal of cancer survivorship : research and practice 15(4): 526-535.
	Purpose: The objective of this review was to assess the efficacy of non-pharmacological interventions on endometrial cancer (EC) survivors' QOL, and their use of patient-reported outcome measures (PROMs).; Methods: We conducted a systematic review of randomized controlled trials (RCTs) of non-pharmacological interventions that assessed the impact of intervention on EC survivors' general and domain-specific QOL (i.e., physical, psychological, and social well-being) using PROMs.; Results: Of the 3178 studies identified, 28 full-text articles were reviewed, and 10 were included in the review. Nine RCTs assessed at least one PROM as a primary outcome and six assessed a PROM as a secondary outcome, but few studies used validated PROMs. Significant improvements in general QOL were found in two studies, domain-specific QOL in three studies, and both general and domain-specific QOL in three studies; however, effect sizes ranged from small to large and no significant effects were found for social well-being and few were found for psychological well-being.; Conclusions: Few non-pharmacological interventions for EC survivors targeted QOL, even though QOL was assessed as either a primary or secondary outcome of the RCT. Despite this, findings suggest that non-pharmacological interventions for EC survivors hold promise for improving general and domain-specific QOL. Use of validated PROMs would greatly enhance outcome reporting and facilitate comparisons across studies. More interventions are also needed that address social and psychological functioning in this population.; Implications for Cancer Survivors: Our review highlights a need to (1) expand non-pharmacological RCTs for EC survivors, (2) increase the use of validated PROMs measuring QOL, and (3) address psychosocial domains of QOL when developing interventions for this population. (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Buckley, B. S., et al. (2019). "Conservative interventions for treating functional daytime urinary incontinence in children." Cochrane Database of Systematic Reviews 2019(9): CD012367.
	Background: In children, functional daytime urinary incontinence is the term used to describe any leakage of urine while awake that is not the result of a known underlying neurological or congenital anatomic cause (such as conditions or injuries that affect the nerves that control the bladder or problems with the way the urinary system is formed). It can result in practical difficulties for both the child and their family and can have detrimental effects on a child's well-being, education and social engagement. Objective(s): To assess the effects of conservative interventions for treating functional daytime urinary incontinence in children. Search Method(s): We searched the Cochrane Incontinence Specialised Register, which contains studies identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 11 September 2018). We also searched Chinese language bibliographic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang. No language restrictions were imposed. Selection Criteria: We included randomised controlled trials (RCTs), quasi-randomised, multi-arm studies, cross-over studies and cluster-randomised studies that included children aged between 5 and 18 years with functional daytime urinary incontinence. Data Collection and Analysis: Two review authors independently screened records and determined the eligibility of studies for inclusion according to predefined criteria. Where data from the study were not provided, we contacted the study authors to request further information. Two review authors assessed risk of bias and processed included study data as described in the Cochrane Handbook for Systematic Reviews of Interventions. Where meta-analysis was possible, we applied random-effects meta-analysis using the Mantel-Haenszel method for dichotomous outcomes. Main Result(s): The review included 27 RCTs involving 1803 children. Of these, six were multi-arm and one was also a cross-over study. Most studies were small, with numbers randomised ranging from 16 to 202. A total of 19 studies were at high risk of bias for at least one domain. Few studies reported data suitable for pooling due to heterogeneity in interventions, outcomes and measurements. Individual conservative interventions (lifestyle, behavioural or physical) versus no treatment. Transcutaneous electrical nerve stimulation (TENS) versus sham (placebo) TENS. More children receiving active TENS may achieve continence (risk ratio (RR) 4.89, 95% confidence interval (CI) 1.68 to 14.21; 3 studies; n = 93; low-certainty evidence). One individual conservative intervention versus another individual or combined conservative intervention. Pelvic floor muscle training (PFMT) with urotherapy versus urotherapy alone. We are uncertain whether more children receiving PFMT with urotherapy achieve continence (RR 2.36, 95% CI 0.65 to 8.53, 95% CI 25 to 100; 3 studies; n = 91; very low-certainty evidence). Voiding education with uroflowmetry feedback and urotherapy versus urotherapy alone. Slightly more children receiving voiding education with uroflow feedback and urotherapy may achieve continence (RR 1.13, 95% CI 0.87 to 1.45; 3 studies; n = 151; low-certainty evidence). Urotherapy with timer watch versus urotherapy alone. We are uncertain whether urotherapy plus timer watch increases the number of children achieving continence compared to urotherapy alone (RR 1.42, 95% CI 1.12 to 1.80; 1 study; n = 58; very low-certainty evidence). Combined conservative interventions versus other combined conservative interventions. TENS and standard urotherapy versus PFMT with electromyographic biofeedback and standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.11, 95% CI 0.73 to 1.68; 1 study; n = 78; very low-certainty evidence). PFMT with electromyography biofeedback and standard urot erapy versus PFMT without feedback but with standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.05, 95% CI 0.72 to 1.52; 1 study; n = 41; very low-certainty evidence). Individual conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions). PFMT versus anticholinergics. We are uncertain whether more children receiving PFMT than anticholinergics achieve continence (RR 1.92, 95% CI 1.17 to 3.15; equivalent to an increase from 33 to 64 per 100 children; 2 studies; n = 86; very low-certainty evidence). TENS versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 0.81, 95% CI 0.05 to 12.50; 2 studies; n = 72; very low-certainty evidence). Combined conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions). Voiding education with uroflowmetry feedback versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportion of children achieving continence (RR 1.02, 95% CI 0.58 to 1.78; 1 study; n = 64; very low-certainty evidence). Authors' conclusions: The review found little reliable evidence that can help affected children, their carers and the clinicians working with them to make evidence-based treatment decisions. In this scenario, the clinical experience of individual clinicians and the support of carers may be the most valuable resources. More well-designed research, with well-defined interventions and consistent outcome measurement, is needed.Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Buda, A., et al. (2022). "Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review." Cancers 14(3).
	Nowadays, the optimal management of patients with cervical cancers measuring 2-4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer, in terms of pathologic response, oncological and obstetric outcomes. The review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, using MEDLINE and PubMed, were searched for from 1 January 2005 up to 1 December 2020. We identified 20 articles and 114 women with IB2 disease, possible candidates for NACT prior to FS surgery. However, uterine conservation was achieved only in 76.7% of them. Patients reached optimal pathological response to NACT in 60.9% of cases and a TIP (cisplatin, ifosfamide and paclitaxel) regime was related to the best response. Suboptimal response to NACT appeared to be an independent negative prognostic factor. Up to 9.2% of patients recurred with a median 7.4-months DFS, and 4.6% of patients died of disease. Fifty percent of women tried to conceive after treatment and NACT prior to conization appeared to be the most promising alternative to upfront radical trachelectomy in terms of obstetric outcomes. In conclusion, NACT prior to FS surgery is an option, but the literature about this issue is still weak and FS should be carefully discussed with patients.

Budani, M. C., et al. (2020). "Efficacy and safety of follitropin alpha biosimilars compared to their reference product: a Meta-analysis." Gynecological Endocrinology: 1-9.
	Aim: Recently published multicentre, randomized phase III studies suggested the therapeutic equivalence of biosimilar follitropin alpha medicaments compared to the reference product. The aim of this meta-analysis is to pool the results of the three phase III trials in order to provide an overall analysis about the clinical bioequivalence between biosimilars and the originator. Method(s): The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) for binary outcomes and the weighted mean difference (WMD) for continuous outcomes along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and Chi-square tests. Result(s): No differences were found in term of number of oocytes retrieved at ovum pick-up, the primary endpoint recommended by the European Medicines Agency. No statistical differences were also found for biochemical pregnancy rate, take home baby rate, total follitropin alpha dose, duration of stimulation, and OHSS risk. A significantly higher clinical pregnancy rate (p =.03) was observed in the originator group in comparison to the biosimilar follitropin alpha. Conclusion(s): Biosimilar follitropin alpha medicaments resulted comparable in comparison to the reference product with respect to the number of oocytes retrieved, that is the primary endpoint recommended by the European Medicines Agency.Further study is needed to evaluate the therapeutic bioequivalence between follitropin alpha biosimilar and the reference medication with respect to secondary endpoints.Copyright © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Buechel, M. E., et al. (2021). "Correlation of imaging and plasma based biomarkers to predict response to bevacizumab in epithelial ovarian cancer (EOC)." Gynecologic Oncology 161(2): 382‐388.
	Purpose: Increasing measures of adiposity have been correlated with poor oncologic outcomes and a lack of response to anti‐angiogenic therapies. Limited data exists on the impact of subcutaneous fat density (SFD) and visceral fat density (VFD) on oncologic outcomes. This ancillary analysis of GOG‐218, evaluates whether imaging markers of adiposity were predictive biomarkers for bevacizumab (bev) use in epithelial ovarian cancer (EOC). Patients and methods: There were 1249 patients (67%) from GOG‐218 with imaging measurements. SFD and VFD were calculated utilizing Hounsfield units (HU). Proportional hazards models were used to assess the association between SFD and VFD with overall survival (OS). Results: Increased SFD and VFD showed an increased HR for death (HR per 1‐SD increase 1.12, 95% CI:1.05–1.19 p = 0.0009 and 1.13, 95% CI: 1.05–1.20 p = 0.0006 respectively). In the predictive analysis for response to bev, high VFD showed an increased hazard for death in the placebo group (HR per 1‐SD increase 1.22, 95% CI: 1.09–1.37; p = 0.025). However, in the bev group there was no effect seen (HR per 1‐SD increase: 1.01, 95% CI: 0.90–1.14) Median OS was 45 vs 47 months in the VFD low groups and 36 vs 42 months in the VFD high groups on placebo versus bev, respectively. Conclusion: High VFD and SFD have a negative prognostic impact on patients with EOC. High VFD appears to be a predictive marker of bev response and patients with high VFD may be more likely to benefit from initial treatment with bev.

Bugge, C., et al. (2020). "The TOPSY pessary self-management intervention for pelvic organ prolapse: a study protocol for the process evaluation." Trials 21(1): 836.
	Background: Process evaluations have become a valued component, alongside clinical trials, of the wider evaluation of complex health interventions. They support understanding of implementation, and fidelity, related to the intervention and provide valuable insights into what is effective in a practical setting by examining the context in which interventions are implemented. The TOPSY study consists of a large multi-centre randomised controlled trial comparing the effectiveness of pessary self-management with clinic-based care in improving women's condition-specific quality of life, and a nested process evaluation. The process evaluation aims to examine and maximise recruitment to the trial, describe intervention fidelity and explore participants' and healthcare professionals' experiences.; Methods: The trial will recruit 330 women from approximately 17 UK centres. The process evaluation uses a mixed-methods approach. Semi-structured interviews will be conducted with randomised women (18 per randomised group/n = 36), women who declined trial participation but agreed to interview (non-randomised women) (n = 20) and healthcare professionals recruiting to the trial (n ~ 17) and delivering self-management and clinic-based care (n ~ 17). The six internal pilot centres will be asked to record two to three recruitment discussions each (total n = 12-18). All participating centres will be asked to record one or two self-management teaching appointments (n = 30) and self-management 2-week follow-up telephone calls (n = 30). Process data (quantitative and qualitative) will be gathered in participant completed trial questionnaires. Interviews will be analysed thematically and recordings using an analytic grid to identify fidelity to the intervention. Quantitative analysis will be predefined within the process evaluation analysis plan.; Discussion: The wide variety of pessary care delivered across the UK for women with pelvic organ prolapse presents specific localised contexts in which the TOPSY interventions will be implemented. Understanding this contextual variance is central to understanding how and in what circumstances pessary self-management can be implemented (should it be effective). The inclusion of non-randomised women provides an innovative way of collecting indispensable information about eligible women who decline trial participation, allowing broader contextualisation and considerations of generalisability of trial findings. Methodological insights from examination of recruitment processes and mechanisms have the potential to inform recruitment mechanisms and future recruitment strategies and study designs.; Trial Registration: ISRCTN62510577 . Registered on 6 October 2017.

Buggio, L., et al. (2022). "Novel pharmacological therapies for the treatment of endometriosis." Expert review of clinical pharmacology 15(9): 1039-1052.
	Introduction: Endometriosis is a chronic, estrogen-dependent, inflammatory disease associated with pelvic pain, infertility, impaired sexual function, and psychological suffering. Therefore, tailored patient management appears of primary importance to address specific issues and identify the appropriate treatment for each woman. Over the years, abundant research has been carried out with the objective to find new therapeutic approaches for this multifaceted disease.; Areas Covered: This narrative review aims to present the latest advances in the pharmacological management of endometriosis. In particular, the potential role of GnRH antagonists, selective progesterone receptor modulators (SPRMs), and selective estrogen receptors modulators (SERMs) will be discussed. We performed a literature search in PubMed and Embase, and selected the best quality evidence, giving preference to the most recent and definitive original articles and reviews.; Expert Opinion: Medical therapy represents the cornerstone of endometriosis management, although few advances have been made in the last decade. Most studies have focused on the evaluation of the efficacy and safety of GnRH antagonists (plus add-back therapy in cases of prolonged treatment), which should be used as second-line treatment options in selected cases (i.e. non-responders to first-line treatments). Further studies are needed to identify the ideal treatment for women with endometriosis.

Buhl, B., et al. (2023). "Food & Fertility Study: study protocol for a Danish multicentre prospective cohort study investigating the association between food intake and semen quality, pregnancy and birth outcomes in infertile women and men." BMJ Open 13(7): e068354.
	Introduction: Worldwide infertility is highly prevalent, and lifestyle factors, such as food intake, could have an essential role in the success of a fertility treatment. The literature is not consistent and adequate for recommendations to the increasing number of women and men of reproductive age who ask for lifestyle guidance. Therefore, the aims of the Food & Fertility Study will be to investigate the possible association between food intake and semen quality in men, and pregnancy and live birth rates in women undergoing intrauterine insemination or assisted reproductive technology treatment.; Methods and Analysis: The Food & Fertility Study is a multicentre prospective cohort study which plans to enrol a total of 4000 women and men between 2022 and 2024. Data collection will take place in four fertility clinics through a web-based Food Frequency Questionnaire. Data on sperm quality and pregnancy and live birth rates will be obtained from medical records and national registers.; Ethics and Dissemination: The study is registered with and approved by the Danish Data Protection Agency, the North Denmark Region (j.nr: 2019-055298). Further, a Statement of Work and a Master Collaboration Agreement have been submitted and approved by the regional legal departments (AGR-2019-731-9667). Dissemination of the results will be through national and international conferences, in scientific environments, in the form of lectures to the broader public, and by peer-reviewed publications in international scientific journals.; Trial Registration Number: NCT05454046.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bui, A., et al. (2022). "Clinical calculator redefines prognosis for high-risk early-stage ovarian cancers and potential to guide treatment in the adjuvant setting." Gynecologic Oncology 167(2): 205-212.
	Objective: To determine the utility of a clinical calculator to redefine prognosis and need for chemotherapy among patients with early-stage high-risk epithelial ovarian cancer.; Methods: Data were abstracted for stage I-II, high-risk ovarian cancer from the National Cancer Database from years 2005 to 2015. Based on demographic, pathologic, surgical, and laboratory characteristics, a clinical score was developed using Cox regression. Propensity score weighting was used to adjust for differences between patients who did and did not receive chemotherapy.; Results: Of 8188 patients with early-stage high-risk ovarian cancer, 6915 (84%) did and 1273 (16%) did not receive chemotherapy. A clinical calculator was created utilizing age, stage, histology, grade, tumor size, number of pelvic and paraaortic lymph nodes examined, the presence of malignant ascites, and CA125. The calculator divided patients into low, moderate, and high-risk groups with 5-year OS (overall survival) of 92%, 82%, and 66%, and 10-year OS of 85%, 67%, and 44%, respectively. Chemotherapy improved 5-year OS and 10-year OS in the high-risk group (56% to 73%; p < 0.001, 34% to 48%; p < 0.001). The moderate risk group had improved 5-year OS (80% to 85%; p = 0.01) but not 10-year OS (66% to 66%; p = 0.13). Chemotherapy did not improve 5-year or 10-year OS in low-risk patients (93% to 92%, p = 1.0, 86% to 84%, p = 0.99).; Conclusions: The prognosis among high-risk early-stage ovarian cancer patients is heterogeneous. This calculator may aid in patient-centered counseling regarding potential treatment benefits.; Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest as it relates to the submitted work. Outside of the submitted work, Dr. Ghamande has received compensation from GlaxoSmithKline for consulting and from Merck as part of their speaker bureau. Dr. Chan has received compensation from Astra Zeneca, Aravive, Clovis, Eisai, GlaxoSmithKline Merck, Myriad, Roche/GenentechSeagen. (Published by Elsevier Inc.)

Buisson, A., et al. (2023). "Retrospective blind assessment of SOPHiA DDM™ Dx HRD solution for evaluation of olaparib maintenance treatment efficacy in ovarian cancer patients from the randomized, phase III PAOLA-1 trial."  483: S55‐S56.
	Background &objectives: SOPHiA DDM™ Dx HRD Solution combines analysis of genomic instability and homologous recombination repair gene mutation status to predict homologous recombination deficiency (HRD) in ovarian cancer (OvCa). As part of the ENGOT HRD initiative, we present updated clinical relevance results. Methods: Using SOPHiA DDM™ Dx HRD Solution, DNA from a subcohort of 359 patients (pts) from the GINECO/ENGOT‐Ov25 PAOLA‐1 trial (NCT02477644) was re‐analysed in a multicentre study. We compared the results to those previously obtained using Myriad myChoice CDx. We investigated differences in progression‐free (PFS) and overall (OS) survival in the olaparib+bevacizumab and placebo+bevacizumab arms between HRD‐positive and HRD‐negative pts. Results: HRD status was determined in 98.9% of pts using SOPHiA DDM™ Dx HRD Solution. The overall concordance with Myriad myChoice CDx was 98.1% (95% confidence interval [CI], 96.0%‐ 99.1%) and highly reproducible across laboratories (r=0.987). In HRD‐positive pts, the PFS and OS time were 55.7 months and 75.2 months respectively in the olaparib+bevacizumab arm versus 18.7 and 56.4 months respectively in the placebo+bevacizumab arm (hazard ratio [HR] PFS, 0.32; 95% CI, 0.22‐0.45, p<0.001; HR OS, 0.49; 95% CI, 0.32‐0.77, p=0.002). No significant difference in PFS or OS was observed between treatment arms in pts with HRD‐negative test (HR PFS, 1.04; 95% CI, 0.71‐1.52; p=0.8; HR OS, 1.19; 95% CI, 0.78‐ 1.80; p=0.4). Conclusion: The analytical performance and the potential clinical relevance results of SOPHiA DDM™ Dx HRD Solution from PAOLA‐1 samples support the value of combining low‐pass whole genome and targeted sequencing in a unique workflow for reliable and decentralized HRD testing and future patient stratification.

Bukkems Leslie, J. H., et al. (2022). "The impact of para-aortic lymph node irradiation on disease-free survival in patients with cervical cancer: A systematic review and meta-analysis." Clinical and translational radiation oncology 35: 97-103.
	Background: Patients with locally advanced cervical cancer without para-aortic lymph node metastases (PAO-LNM) at diagnosis who undergo concurrent chemoradiotherapy are at 4-11% risk of developing PAO-LNM during follow-up. Some studies suggest a beneficial influence of elective para-aortic radiotherapy (PAO-RT) on disease-free survival (DFS) in these patients. The aim of this study was to systematically review and meta-analyse literature on the impact of PAO-RT on DFS in cervical cancer patients.; Methods: A systematic search of PubMed/MEDLINE and EMBASE databases was performed. The analysis included intervention studies that reported on DFS in patients with cervical cancer who received chemotherapy and pelvic radiotherapy with or without PAO-RT. From each included study, relevant study characteristics and outcome data including the hazard ratio (HR) adjusted for potential confounders were extracted. An overall pooled adjusted hazard ratio (aHR) for DFS after PAO-RT versus no PAO-RT was calculated using a random-effects model.; Results: A total of 2,016 articles were evaluated. Eleven articles were included in the systematic review, of which 3 were appropriate for quantitative meta-analysis. Pooling of these 3 cohorts (including 1,113 patients) demonstrated a statistically significant association between PAO-RT and DFS (pooled aHR 0.87, 95% confidence interval: 0.79-0.97). No significant heterogeneity among reported aHRs was observed (I 2 = 0.0%).; Conclusions: This meta-analysis suggests a modest but significant beneficial impact of elective para-aortic radiotherapy on DFS in patients with locally advanced cervical cancer who undergo concurrent chemoradiotherapy. This finding based on non-randomized studies provides an imperative for further investigation in prospective controlled trials.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Author(s).)

Bülow Nathalie, S., et al. (2022). "Co-treatment with letrozole during ovarian stimulation for IVF/ICSI: a systematic review and meta-analysis." Reproductive Biomedicine Online 44(4): 717-736.
	Letrozole reduces serum oestradiol by inhibiting the aromatase enzyme and has growing clinical indications in fertility. The available evidence of letrozole's role in ovarian stimulation for IVF and intracytoplasmic sperm injection (ICSI) and clinical outcomes was assessed. Medline, Cochrane, and ClinicalTrials.gov databases were systematically searched up until August 2021, including 31 studies (n = 16 randomized controlled trials [RCTs]; n = 15 observational studies). Live birth rate (LBR) in poor responders significantly increased by 7% (95% CI, 1% to 13%, P = 0.03) with letrozole co-treatment. Concomitantly, the gonadotrophin consumption was significantly reduced, without decreasing the number of retrieved oocytes. In normal responders, number of oocytes increased with 1.8 oocytes (95% CI 0.35 to 3.27, P = 0.01) with letrozole co-treatment. No significant effect on LBR, clinical pregnancy rate (CPR), or ovarian hyperstimulation syndrome rate was demonstrated. Only two studies reported on high responders and revealed no effect on LBR or CPR. Overall, the endometrium thickness was slightly affected, where as the, miscarriage rate and cancellation rate were unaffected by letrozole co-treatment. None of the included studies reported on neonatal outcomes. The quality of evidence was high or moderate in the RCTs and low in the observational studies. In conclusion, poor responders may benefit from co-treatment with letrozole during ovarian stimulation for IVF, whereas letrozole for normal and high responders requires further investigation with larger, high-quality studies. (Copyright © 2021 Reproductive Healthcare Ltd. All rights reserved.)

Buonomo, B., et al. (2021). "Ovarian transposition in patients with cervical cancer prior to pelvic radiotherapy: a systematic review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(3): 360-370.
	Ovarian transposition aims to minimize ovarian exposure and damage during pelvic radiotherapy. One or both ovaries are separated from the uterus and mobilized away from the area where the radiation will be administered. A review of the available literature was conducted to evaluate the efficacy and safety of ovarian transposition among pre-menopausal women diagnosed with cervical cancer and eligible for pelvic radiotherapy. Outcomes evaluated were ovarian function preservation and complication rates. We also searched for information on pregnancy/live birth rates after ovarian transposition. Our search yielded a total of 635 manuscripts, of which 33 were considered eligible. A total of 28 full texts were selected for the current review, including 1377 patients who underwent ovarian transposition. The median or mean follow-up ranged between 7 and 87 months. Ovarian function preservation after ovarian transposition and pelvic radiotherapy, with or without chemotherapy, was 61.7% (431/699 patients), ranging from 16.6% to 100%. A total of 12 studies reported on 117 complications, accounting for 8.5%. Ovarian metastases were described in 5 (0.4%). Data about fertility preservation after ovarian transposition are scarce and definitive conclusions cannot be drawn. Based on the available data, ovarian transposition could be performed on young patients with tumors smaller than 4 cm, and it should be avoided in those with bulky tumors. A risk/benefit assessment should be carefully evaluated by a multidisciplinary team, and the decision regarding ovarian transposition should be always guided by the values and informed preferences of the patient.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Burbano, J., et al. (2021). "Neoadjuvant chemotherapy prior to fertility-sparing surgery in cervical tumors larger than 2 cm: a systematic review on fertility and oncologic outcomes." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(3): 387-398.
	Background: Management of cervical cancer tumors >2 cm has been a subject of controversy, with management often considered as either up-front radical trachelectomy or neoadjuvant chemotherapy before fertility-sparing surgery.; Methods: A systematic literature review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline through PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID between January 1985 and December 2020. Eligibility criteria for selecting studies were English language, randomized controlled trials, and observational studies including information on fertility and oncologic outcomes. All titles were managed in EndNote X7. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies.; Results: Twenty-three studies with 205 patients who received neoadjuvant chemotherapy were included. The majority of patients (92.2%, n=189) had stage IB FIGO 2009 cervical cancer. The preferred regimen used was cisplatin in combination with paclitaxel or ifosfamide (80%, n=164). One hundred and eighty patients (87.8%) underwent fertility-sparing surgery; radical vaginal trachelectomy, abdominal trachelectomy, conization, and simple trachelectomy were performed in 62 (34.4%), 49 (27.2%), 34 (18.9%), and 26 (14.4%) women, respectively. In nine patients (5%) the type of procedure was not specified. The follow-up time reported in all studies ranged between 6 and 69 months. In 112 women who sought a pregnancy after surgery, 84.8% (n=95) achieved a gestation.The global recurrence and death rates were 12.8% and 2.8%, respectively.; Conclusion: Neoadjuvant chemotherapy followed by fertility-sparing surgery is a promising strategy that might allow fertility preservation in highly selected patients with cervical cancer with tumors >2 cm while providing acceptable oncologic outcomes. Results of prospective studies are required to validate its oncological safety.; Systematic Review Registration Number: PROSPERO CRD42020203789.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Burçin, Ö., et al. (2022). "The effectiveness of Yoga method for pelvic floor dysfunction."
	
Burden, S., et al. (2019). "Dietary interventions for adult cancer survivors." Cochrane Database of Systematic Reviews 2019(11): CD011287.
	Background: International dietary recommendations include guidance on healthy eating and weight management for people who have survived cancer; however dietary interventions are not provided routinely for people living beyond cancer. Objective(s): To assess the effects of dietary interventions for adult cancer survivors on morbidity and mortality, changes in dietary behaviour, body composition, health-related quality of life, and clinical measurements. Search Method(s): We ran searches on 18 September 2019 and searched the Cochrane Central Register of Controlled trials (CENTRAL), in the Cochrane Library; MEDLINE via Ovid; Embase via Ovid; the Allied and Complementary Medicine Database (AMED); the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and the Database of Abstracts of Reviews of Effects (DARE). We searched other resources including reference lists of retrieved articles, other reviews on the topic, the International Trials Registry for ongoing trials, metaRegister, Physicians Data Query, and appropriate websites for ongoing trials. We searched conference abstracts and WorldCat for dissertations. Selection Criteria: We included randomised controlled trials (RCTs) that recruited people following a cancer diagnosis. The intervention was any dietary advice provided by any method including group sessions, telephone instruction, written materials, or a web-based approach. We included comparisons that could be usual care or written information, and outcomes measured included overall survival, morbidities, secondary malignancies, dietary changes, anthropometry, quality of life (QoL), and biochemistry. Data Collection and Analysis: We used standard Cochrane methodological procedures. Two people independently assessed titles and full-text articles, extracted data, and assessed risk of bias. For analysis, we used a random-effects statistical model for all meta-analyses, and the GRADE approach to rate the certainty of evidence, considering limitations, indirectness, inconsistencies, imprecision, and bias. Main Result(s): We included 25 RCTs involving 7259 participants including 977 (13.5%) men and 6282 (86.5%) women. Mean age reported ranged from 52.6 to 71 years, and range of age of included participants was 23 to 85 years. The trials reported 27 comparisons and included participants who had survived breast cancer (17 trials), colorectal cancer (2 trials), gynaecological cancer (1 trial), and cancer at mixed sites (5 trials). For overall survival, dietary intervention and control groups showed little or no difference in risk of mortality (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.77 to 1.23; 1 study; 3107 participants; low-certainty evidence). For secondary malignancies, dietary interventions versus control trials reported little or no difference (risk ratio (RR) 0.99, 95% CI 0.84 to 1.15; 1 study; 3107 participants; low-certainty evidence). Co-morbidities were not measured in any included trials. Subsequent outcomes reported after 12 months found that dietary interventions versus control probably make little or no difference in energy intake at 12 months (mean difference (MD) -59.13 kcal, 95% CI -159.05 to 37.79; 5 studies; 3283 participants; moderate-certainty evidence). Dietary interventions versus control probably led to slight increases in fruit and vegetable servings (MD 0.41 servings, 95% CI 0.10 to 0.71; 5 studies; 834 participants; moderate-certainty evidence); mixed results for fibre intake overall (MD 5.12 g, 95% CI 0.66 to 10.9; 2 studies; 3127 participants; very low-certainty evidence); and likely improvement in Diet Quality Index (MD 3.46, 95% CI 1.54 to 5.38; 747 participants; moderate-certainty evidence). For anthropometry, dietary intervention versus control probably led to a slightly decreased body mass index (BMI) (MD -0.79 kg/m2, 95% CI -1.50 to -0.07; 4 studies; 777 participants; moderate-certainty evidence). Dietary interventions versus control probably had little or no effect on waist-to-hip ratio (MD -0.01, 95% CI -0.04 to 0.02; 2 studies; 106 participants; low-ce tainty evidence). For QoL, there were mixed results; several different quality assessment tools were used and evidence was of low to very low-certainty. No adverse events were reported in any of the included studies. Authors' conclusions: Evidence demonstrated little effects of dietary interventions on overall mortality and secondary cancers. For comorbidities, no evidence was identified. For nutritional outcomes, there was probably little or no effect on energy intake, although probably a slight increase in fruit and vegetable intake and Diet Quality Index. Results were mixed for fibre. For anthropometry, there was probably a slight decrease in body mass index (BMI) but probably little or no effect on waist-to-hip ratio. For QoL, results were highly varied. Additional high-quality research is needed to examine the effects of dietary interventions for different cancer sites, and to evaluate important outcomes including comorbidities and body composition. Evidence on new technologies used to deliver dietary interventions was limited.Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Burg, L. C., et al. (2021). "A cost-effectiveness analysis of three approaches for lymph node assessment in patients with low- and intermediate-risk endometrial cancer." Gynecologic Oncology 161(1): 251-260.
	Objective: To assess the cost-effectiveness of sentinel lymph node mapping compared to risk factor assessment and routine full lymph node dissection for the assessment of lymph nodes in patients with low- and intermediate-risk endometrioid endometrial cancer. Method(s): A decision-analytic model was designed to compare three lymph node assessment strategies in terms of costs and effects: 1) sentinel lymph node mapping; 2) post-operative risk factor assessment (adjuvant therapy based on clinical and histological risk factors); 3) full lymph node dissection. Input data were derived from systematic literature searches and expert opinion. QALYs were used as measure of effectiveness. The model was built from a healthcare perspective and the impact of uncertainty was assessed with sensitivity analyses. Result(s): Base-case analysis showed that sentinel lymph node mapping was the most effective strategy for lymph node assessment in patients with low- and intermediate-risk endometrial cancer. Compared to risk factor assessment it was more costly, but the incremental cost effectiveness ratio stayed below a willingness-to-pay threshold of 20,000 with a maximum of 9637/QALY. Sentinel lymph node mapping was dominant compared to lymph node dissection since it was more effective and less costly. Sensitivity analyses showed that the outcome of the model was robust to changes in input values. With a willingness-to-pay threshold of 20,000 sentinel lymph node mapping remained cost-effective in at least 74.3% of the iterations. Conclusion(s): Sentinel lymph node mapping is the most cost-effective strategy to guide the need for adjuvant therapy in patients with low and intermediate risk endometrioid endometrial cancer.Copyright © 2021 The Authors

Burger, Z., et al. (2021). "Association of levonorgestrel intrauterine devices with stress reactivity, mental health, quality of life and sexual functioning: A systematic review." Frontiers in Neuroendocrinology 63: 100943.
	Levonorgestrel-intrauterine-devices (LNG-IUD) are one of the most used contraceptive methods worldwide. While several reviews exist on how LNG-IUDs impact physiology and gynaecological functions, this systematic review focuses on stress, mental health, quality of life, sexual functioning, and effects on brain architecture. While data on stress is scarce, results on mental health are ambiguous. More consistently, LNG-IUD use seems to improve quality of life and sexual functioning. No studies highlighting the consequences of LNG-IUD use on the brain were found. The reviewed studies are characterized by a substantial variation in approaches, participant groups, and study quality. More high-quality research assessing the effects of LNG-IUD on mental health, including response to stressors and brain function and structure, is needed to identify women vulnerable to adverse effects of LNG-IUD, also in comparison to oral contraceptives, and to empower women to make more informed choices concerning hormonal contraception.Copyright © 2021 Elsevier Inc.

Burghaus, S. and W. Beckmann Matthias (2021). "[Endometriosis: gynecological diagnosis and treatment : What should pain management specialists know?]." Schmerz (Berlin, Germany) 35(3): 172-178.
	Background: Endometriosis is one of the most common diseases in women of reproductive age. Despite characteristic symptoms such as dysmenorrhea, chronic abdominal pain, dysuria, dyschezia and dyspareunia, the average latency until diagnosis is around 10 years. In addition to the individual limitations, the disease also has economic and health policy relevance. The complaints are followed by reductions in working hours, cyclically recurring short-term sick leave or presenteeism with reduced performance.; Objective: An overview of the main recommendations of the S2k guideline on the diagnosis and treatment of endometriosis.; Material and Methods: For the S2k guideline "Diagnostics and therapy of endometriosis", a systematic literature search was conducted in PubMed and Cochrane according to a defined algorithm and over a period of more than 5 years, from 01.01.2014 to 31.12.2018. For the evaluation, 322 publications, including systematic reviews, meta-analyses and randomized controlled trials were considered and these were assessed by 41 mandate holders and representatives from 25 Association of the Scientific Medical Societies in Germany (AWMF) and non-AWMF professional societies, organizations, associations and working groups of the German Society for Gynecology and Obstetrics (DGGG), as well as two patient target groups.; Results: In a structured consensus process, 48 recommendations and 27 statements were formulated, which are presented in extracts in this paper.; Discussion: Interdisciplinary cooperation is essential in the treatment of patients with (suspected) endometriosis. This team should include all necessary disciplines in a cross-sectoral network. This is most likely to be achieved in a certified structure.

Burks, C., et al. (2021). "Excision versus Ablation for Management of Minimal to Mild Endometriosis: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(3): 587-597.
	Objective: The aim of this systematic review and meta-analysis was to perform an updated analysis of the literature in regard to the surgical management of minimal to mild endometriosis. This study evaluated women of reproductive age with superficial endometriosis to determine if the results of surgical excision compared with those of ablation in improved pain scores postoperatively.; Data Sources: The following databases were searched from inception to May 2020 for relevant studies: Cochrane Central Register of Controlled Trials, PubMed (MEDLINE), Ovid (MEDLINE), Scopus, and Web of Science.; Methods of Study Selection: From our literature search, a total of 2633 articles were identified and screened. Ultimately, 4 randomized controlled trials were selected and included in our systematic review. The combined total number of subjects was 346 from these 4 studies, with sample sizes ranging from 24 to 170 participants. Data from 3 of the included studies were able to be compared and analyzed for a meta-analysis. The primary outcome was reduction in the visual analog scale (VAS) score for endometriosis-associated pain (dysmenorrhea, dyschezia, and dyspareunia), with follow-up time ranging from 6 to 60 months postoperatively.; Tabulation, Integration, and Results: Data extracted from each study included the mean reduction in the VAS score from baseline. A random-effects model was used owing to significant heterogeneity across the studies. Statistical analyses were performed using Review Manager 5.3 software (Cochrane Collaboration, London, United Kingdom). The meta-analyses showed no significant differences between the excision and ablation groups in the mean reduction in VAS scores from baseline to 12 months postoperatively for dysmenorrhea (mean difference [MD] -0.03; 95% confidence interval [CI], -1.27 to 1.22; p = .97), dyschezia (MD 0.46; 95% CI, -1.09 to 2.02; p = .56), and dyspareunia (MD 0.10; 95% CI, -2.36 to 2.56; p = .94). In addition, there were no significant differences between the excision and ablation groups in mean VAS scores at the 12-month follow-up and beyond for dysmenorrhea (MD -0.11; 95% CI, -2.14 to 1.93; p = .92), dyschezia (MD 0.01; 95% CI, -0.70 to 0.72; p = .99), and dyspareunia (MD 0.34; 95% CI, -1.61 to 2.30; p = .73).; Conclusion: On the basis of the data from our systematic review and pooled meta-analysis, no significant difference between laparoscopic excision and ablation was noted in regard to improving pain from minimal to mild endometriosis. However, to make definitive conclusions on this topic, larger randomized controlled trials are needed with longer follow-up. (Copyright © 2020. Published by Elsevier Inc.)

Burt, L., et al. (2022). "SHORT COURSE ADJUVANT VAGINAL CUFF BRACHYTHERAPY IN EARLY ENDOMETRIAL CANCER: ADVERSE EVENTS AND EARLY PATIENT REPORTED OUTCOMES." International Journal of Gynecological Cancer 32(Supplement 3): A12.
	Objectives Adjuvant vaginal cuff brachytherapy (VCB) improves vaginal control rates in early stage endometrial cancer. We propose a shorter course of VCB would be non-inferior in safety, efficacy and quality of life metrics compared to standard course VCB. Methods This multi-institutional trial randomized early stage endometrial patients to adjuvant short course VCB (11 Gy x 2 fractions to the surface delivered a week apart) or the standard of care VCB (either 6 Gy x 5 fractions to the surface, 7 Gy x 3 fractions or 5-5.5 Gy x 4 fractions at 0.5 cm depth). All patients underwent hysterectomy with pathologically confirmed endometrioid adenocarcinoma, serous, clear cell or carcinosaroma histology. Eligible patients included all FIGO IB or II, FIGO 1A gr 2 -3 or FIGO 1A gr 1 with LVSI. Primary endpoint was health related quality of life (HRQOL) using the Global Health Score from the QLQ-C30 at 1 month. Results There were 108 patients enrolled from 5 institutions. At a median follow-up of 12.85 months, there have been no isolated vaginal recurrences. Table 1 shows the distribution of recurrences. Adverse events are shown in table 2. At the 1 month and 6 month time point, the QLQ-C30 scores in the experimental arm were non-inferior (P= p=0.00002). Conclusions This prospective randomized trial showed short course VCB is non-inferior to standard course VCB. While longer follow up data is necessary, short course VCB supports a growing literature in providing more options for women with early stage endometrial cancer.

Burton, J., et al. (2024). Effect of PreforPro® on Urinary and Vaginal Health.
	No Results Available Drug: Preforpro|Other: Placebo To change Nugent score in women with intermediate grade or BV|Determine whether the bacteriophage can translocate from the gastrointestinal system to genitourinary system.|Determine if the microbiota in the gut and urinary system change|Determine change in vaginal cell exfoliation.|Determine whether probiotics can translocate from the gastrointestinal system to genitourinary system.|Determine change in urogenital ATP levels. Female Phase 3 50 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment BVPFB2021 June 1, 2025

Busnelli, A., et al. (2022). "Impact of Thyroid Autoimmunity on Assisted Reproductive Technology Outcomes and Ovarian Reserve Markers: An Updated Systematic Review and Meta-Analysis." Thyroid : official journal of the American Thyroid Association 32(9): 1010-1028.
	Background: Thyroid autoimmunity (TAI) has a high prevalence among women of reproductive age. Investigating its possible impact on ovarian function and fertility is, thus, of utmost relevance. The aim of this systematic review and meta-analysis was to elucidate the effect of TAI on both assisted reproductive technology (ART) outcomes and ovarian reserve. Methods: This systematic review and meta-analysis was restricted to two groups of research articles investigating the association between TAI and: (1) autologous ART outcomes (i.e., fertilization rate [FR], implantation rate, clinical pregnancy rate [CPR], miscarriage rate, and live birth rate), (2) markers of ovarian reserve (i.e., anti-Müllerian hormone, basal follicle stimulating hormone, antral follicle count, and number of oocytes retrieved). Studies including women affected by overt hypo/hyperthyroidism were excluded. Relevant studies were identified by a systematic search in PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus, from database inception to May 1, 2022. Results: From a total of 432 identified publications, 22 studies were included in Group 1 and 26 studies in Group 2. The presence of TAI was associated with a higher risk of miscarriage (7606 participants, odds ratio [OR] 1.52, confidence interval [CI 1.14-2.01], p = 0.004, I 2 = 53%), lower chance of embryo implantation (7118 participants, OR 0.72, [CI 0.59-0.88], p = 0.001, I 2 = 36%), and live birth (11417 participants, OR 0.73, [CI 0.56-0.94], p = 0.02, I 2 = 71%). These associations were no longer observed in a subgroup analysis of patients who exclusively underwent intracytoplasmic sperm injection (ICSI). The FR and CPR as well as the mean values of surrogate markers of oocyte quantity appeared not to be affected by TAI. Conclusions: This data synthesis suggest a higher risk of adverse ART outcomes in women with positive TAI. However, the reliability of these findings is hampered by the relatively low quality of the evidence and significant heterogeneity in many of the meta-analyses. The possible protective effect of ICSI is promising but should be confirmed in controlled prospective clinical trials. PROSPERO Registration ID : CRD42021236529.

Busnelli, A., et al. (2021). "Thyroid function modifications in women undergoing controlled ovarian hyperstimulation for in vitro fertilization: a systematic review and meta-analysis." Fertility and Sterility 116(1): 218-231.
	Objective: To investigate the impact of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) on thyroid function.; Design: Systematic review and meta-analysis.; Setting: Not applicable.; Patient(s): Infertile women undergoing conventional IVF or intracytoplasmic sperm injection.; Intervention(s): Systematic search of PubMed, MEDLINE, Embase, Scopus, and Web of Science from inception until November 2020. Studies could be included only if they met the following criteria: subjects were classified as euthyroid or hypothyroid; serum thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) levels were evaluated before COH; and the same thyroid function test was reassessed after COH (i.e., at the time of trigger for final follicle maturation and/or at pregnancy test).; Main Outcome Measure(s): Mean difference (MD) between the serum TSH or FT4 levels assessed after COH and before COH.; Result(s): In euthyroid women, the serum TSH levels assessed at the time of trigger and at the time of pregnancy test were significantly higher than those at baseline (MD: 0.69 mIU/L, 95% confidence interval [CI]: 0.30-1.08, I 2 = 93% and MD: 0.67, 95% CI: 0.49-0.85, I 2 = 72%, respectively). The serum FT4 levels did not undergo significant changes. Subanalysis confirmed an increase in the TSH level after restricting the analysis to women treated with gonadotropin-releasing hormone agonist protocols and to those who achieved pregnancy. A pronounced increase in the TSH level was observed in women treated for hypothyroidism (MD: 1.50 mIU/L, 95% CI: 1.10-1.89, I 2 = 0%).; Conclusion(s): Pooling of the results showed a significant increase in serum TSH level in women undergoing COH for IVF. This change was particularly pronounced in women treated for hypothyroidism. New thyroid function screening strategies for women undergoing COH are warranted. (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Butina, L. I., et al. (2022). "CLINICAL AND MORPHOLOGICAL FEATURES OF POST-CASTRATION SYNDROME IN WOMEN AFTER SURGICAL MENOPAUSE." Reproductive Endocrinology(63-64): 92-96.
	Research objective: to assess the clinical and morphological features of the course of post-castration syndrome (PS) in women after surgical menopause. Materials and methods. The main group (with surgical menopause) consisted of 67 women aged 45 to 55 years, who underwent surgical treatment with removal of the uterus with or without appendages. 30 women with natural menopause were included in the comparison group. The assessment of morphological changes in the reproductive organs in both groups was carried out according to the results of the histological examination of reproductive organs removed during the operation, and according to the results of the pathological examination of endometrium after curettage of uterine mucosa. Results. The leading indication for surgical treatment, which led to surgical menopause, was uterine leiomyoma in 71.1% of women. Extirpation of the uterus was performed in 64.2% of patients, complete exclusion of ovarian function was observed in 68.7%. There was a deficiency of estrogen in women with surgical menopause, even before the operation, as evidenced by the presence of morphological signs of hypoestrogenism in the form of endometrial atrophy in 41.8% of them, which is 6.2 times (p < 0.001) more often compared with women with natural menopause. The morphological signs of the inflammatory process in reproductive organs in more than half of women with surgical menopause (significantly more than in women with natural menopause, p < 0.001) increase the likelihood of depletion of the ovarian hormonal function and increase the intensity of PS symptoms. This is evidenced by a significant 2.8-fold increase in women with surgical menopause in the frequency of severe PS and the median of the modified Kupperman index compared with women with natural menopause (p < 0.001). The decrease in the ovarian hormonal function in women after surgical menopause increases the frequency of ovarian cysts by 12 times compared with women with natural menopause (p < 0.001). Conclusions. It is necessary to establish the significance of the investigated clinical and morphological features observed in women with surgical menopause to predict the severity of PS in them.Copyright © 2022 Trylyst. All rights reserved.

Butt Muhammad, S., et al. (2023). "Benefits of physical activity on reproductive health functions among polycystic ovarian syndrome women: a systematic review." BMC public health 23(1): 882.
	Background: Polycystic ovary syndrome (PCOS) is among the predominant endocrine disorders of reproductive-aged women. The prevalence of PCOS has been estimated at approximately 6-26%, affecting 105 million people worldwide. This systematic review aimed to synthesize the evidence on the effects of physical activity on reproductive health functions among PCOS women.; Methods: The systematic review includes randomization-controlled trials (RCTs) on physical exercise and reproductive functions among women with PCOS. Studies in the English language published between January 2010 and December 2022 were identified via PubMed. A combination of medical subject headings in terms of physical activity, exercise, menstrual cycle, hyperandrogenism, reproductive hormone, hirsutism, and PCOS was used.; Results: Overall, seven RCTs were included in this systematic review. The studies investigated interventions of physical activity of any intensity and volume and measured reproductive functions and hormonal and menstrual improvement. The inclusion of physical activity alone or in combination with other therapeutic interventions improved reproductive outcomes.; Conclusion: The reproductive functions of women with PCOS can be improved with physical activity. Furthermore, physical activity can also reduce infertility, as well as social and psychological stress among women.; Prospero Systematic Review Registration: CRD42020213732. (© 2023. The Author(s).)

Buultjens, M., et al. (2021). "The contribution of group prenatal care to maternal psychological health outcomes: A systematic review." Women and Birth 34(6): e631-e642.
	Problem: Poor mental health remains a significant cause of morbidity for childbearing women globally. Background(s): Group care has been shown to be effective in reducing select clinical outcomes, e.g., the rate of preterm birth, but less is known about the effect of Group Prenatal Care (GPC) on mental health outcomes of stress, depression and anxiety in pregnant women. Aim(s): To conduct a systematic review of the current evidence of the effect of group pregnancy care on mental health and wellbeing outcomes (i.e., stress, depression and/or anxiety) in childbearing women. Method(s): A comprehensive search of published studies in Medline, PsychInfo, CINAHL, ProQuest databases, ClinicalTrials.gov and Google Scholar. Databases were systematically searched without publication period restriction until Feb 2020. Inclusion criteria were randomized controlled trials (including quasi-experimental) and observational studies comparing group care with standard pregnancy care. Included were studies published in English, whose primary outcome measures were stress, depression and/or anxiety. Result(s): Nine studies met the inclusion criteria, five randomized controlled trials and four observational studies, involving 1585 women (39%) in GPC and 2456 women (61%) in standard (individual) pregnancy care. Although evidence is limited, where targeted education was integrated into the group pregnancy care model, significant reductions in depressive symptoms were observed. In addition, secondary analysis across several studies identified a subset of GPC women, i.e., higher risk for psychological symptoms, who reported a decrease in their depression, stress and anxiety symptoms, postpartum. Due to the diversity of group care structure and content and the lack of outcomes measures universally reported, a comprehensive meta-analysis could not be performed. Conclusion(s): The evidence suggests improvements in some markers of psychological health outcomes with group pregnancy care. Future research should involve larger well-designed studies encompassing cross-population data using a validated scale that is comparable across diverse childbearing populations and clinical settings to better understand the impact of group pregnancy care.Copyright © 2020 Australian College of Midwives

Buzzaccarini, G., et al. (2021). "Hyaluronic acid in vulvar and vaginal administration: evidence from a literature systematic review." Climacteric 24(6): 560-571.
	Vulvovaginal pathology impairs the quality of life of both women in menopause and those who are not. Different therapies have been proposed, mainly related to estrogen therapy in postmenopausal women. However, some contraindications limit its use, and different moisturizers or lubricants have been tested. Hyaluronic acid is a promising and widely used vaginal medical treatment with a moisturizing action and appears to provide a solution. For this reason, we performed a systematic review of the literature. We searched for original articles without date restriction until 30 April 2020. We included all clinical trials which administered local hyaluronic acid in the vulva or vagina. Only English studies and those performed in humans were eligible. Seventeen original studies were included in the review (from randomized controlled trials to longitudinal studies). Hyaluronic acid was generally found to be effective in improving vulvovaginal symptoms (dyspareunia, itching, burning, dryness) and signs (bleeding, atrophy, vaginal pH). In conclusion, hyaluronic acid has the properties to be an efficient moisturizer for women suffering from vulvovaginal atrophy who have contraindications for estrogen therapy and for vulvovaginal signs and symptoms affecting sexual well-being. However, a well-designed randomized controlled trial is needed in order to clarify its efficacy and safety profile.Copyright © 2021 International Menopause Society.

bvrzp, R. B. R. (2022). "Effect of Pilates compared to Pelvic Floor Muscle Training on urinary incontinence, pelvic floor muscle strength and respiratory in elderly women: a randomized clinical trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: E02.760.169.063.500.387.750 E02.779.474 G11.427.410.698 G11.427.410.698.277 This is a two‐arm, double‐blind, randomized controlled clinical trial. Experimental group: 17 elderly women with symptoms of stress urinary incontinence who will receive Mat Pilates sessions twice a week lasting 60 minutes each, for 3‐4 months. Control group: 17 elderly women with symptoms of stress urinary incontinence who will receive pelvic floor muscle training (PFM) sessions for 3‐4 months, twice a week, lasting 30 minutes. CONDITION: M01.060.116.100 Pelvic Floor; Urinary Incontinence PRIMARY OUTCOME: It is expected to find an improvement in respiratory muscle strength, represented by the increase in inspiratory and expiratory pressures measured in cmH2o and evaluated through manovacuometry, after the intervention period. It is expected to find an improvement in urinary leakage symptoms, represented by the decrease in the ICIQ‐SF score after the intervention period It is expected to find improvement in pelvic floor muscle strength, assessed through perineometry and represented by the increase in cmH2O values after the intervention period SECONDARY OUTCOME: Secondary outcomes are not expected INCLUSION CRITERIA: Being female; being between 60 – 79 years of age; presence of voluntary contraction of the pelvic floor muscles at least grade 2 defined as weak perineal contraction weak contraction on palpation; preserved cognitive function verified by the Mini Mental State Examination (MMSE) scored according to education level

Byatt, N., et al. (2022). "The PRogram in Support of Moms (PRISM): Results of A Cluster Randomized Controlled Trial of Two Active Interventions Addressing Perinatal Depression in Ambulatory Obstetric Settings." Journal of the Academy of Consultation-Liaison Psychiatry 63(Supplement 2): S232.
	2022 Dlin/Fischer Clinical Research Award Winner Abstract. Objective(s): We compared the effectiveness of two active interventions for perinatal depression. Method(s): We conducted a cluster randomized controlled trial. Ten Ob/Gyn practices were randomly assigned to receive (1) the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms, a state-wide, population-based program, and (2) the PRogram In Support of Moms (PRISM) which includes MCPAP for Moms plus a proactive, multifaceted, obstetric practice-level intervention with intensive implementation support. Patient participants (n=312) with Edinburgh Postnatal Depression Scale Scores (EPDS) >= 10 were recruited from participating practices and followed up to 11-13 months postpartum. Differences in depression symptomatology and treatment participation among patient participants were compared by intervention group. Generalized estimating equations were used to examine treatment initiation in MCPAP for Moms versus PRISM. Result(s): EPDS scores decreased by 4.5 in the MCPAP for Moms groups and 4.7 points in the PRISM group at 11-13 months postpartum as compared to baseline. Treatment initiation rates were 57% in the PRISM group and 50% MCPAP for Moms group. No statistically significant differences in depression symptomatology or treatment initiation were found between the groups. However, 32% of patient participants in the PRISM group sustained treatment compared with 22% in the MCPAP for Moms group. Conclusion(s): Both MCPAP for Moms and PRISM are effective in improving depression symptomology, and treatment initiation and sustainment rates. This finding is important because 1) 4-point decrease in EPDS is clinically significant, and 4) MCPAP for Moms was equally as effective as PRISM but is lower intensity and has greater population-based reach.Copyright © 2022

Byatt, N., et al. (2024). "Effectiveness of two systems-level interventions to address perinatal depression in obstetric settings (PRISM): an active-controlled cluster-randomised trial." The Lancet. Public health 9(1): e35-e46.
	BACKGROUND: Perinatal depression is a common and undertreated condition, with potential deleterious effects on maternal, obstetric, infant, and child outcomes. We aimed to compare the effectiveness of two systems-level interventions in the obstetric setting-the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms and the PRogram In Support of Moms (PRISM)-in improving depression symptoms and participation in mental health treatment among women with perinatal depression. METHODS: In this cluster-randomised, active-controlled trial, obstetric practices across Massachusetts (USA) were allocated (1:1) via covariate adaptive randomisation to either continue participating in the MCPAP for Moms intervention, a state-wide, population-based programme, or to participate in the PRISM intervention, which involved MCPAP for Moms plus a proactive, multifaceted, obstetric practice-level intervention with intensive implementation support. English-speaking women (aged ≥18 years) who screened positive for depression (Edinburgh Postnatal Depression Scale [EPDS] score ≥10) were recruited from the practices. Patients were followed up at 4-25 weeks of gestation, 32-40 weeks of gestation, 0-3 months postpartum, 5-7 months postpartum, and 11-13 months postpartum via telephone interview. Participants were masked to the intervention; investigators were not masked. The primary outcome was change in depression symptoms (EPDS score) between baseline assessment and 11-13 months postpartum. Analysis was done by intention to treat, fitting generalised linear mixed models adjusting for age, insurance status, education, and race, and accounting for clustering of patients within practices. This trial is registered with ClinicalTrials.gov, NCT02760004. FINDINGS: Between July 29, 2015, and Sept 20, 2021, ten obstetric practices were recruited and retained; five (50%) practices were randomly allocated to MCPAP for Moms and five (50%) to PRISM. 1265 participants were assessed for eligibility and 312 (24·7%) were recruited, of whom 162 (51·9%) were enrolled in MCPAP for Moms practices and 150 (48·1%) in PRISM practices. Comparing baseline to 11-13 months postpartum, EPDS scores decreased by 4·2 (SD 5·2; p<0·0001) among participants in MCPAP for Moms practices and by 4·3 (SD 4.5; p<0·0001) among those in PRISM practices (estimated difference between groups 0·1 [95% CI -1·2 to 1·4]; p=0·87). INTERPRETATION: Both the MCPAP for Moms and PRISM interventions were equally effective in improving depression symptoms. This finding is important because the 4-point decrease in EPDS score is clinically significant, and MCPAP for Moms has a lower intensity and greater population-based reach than does PRISM. FUNDING: US Centers for Disease Control and Prevention.

Byatt, N., et al. (2019). "Perinatal depression care pathway for obstetric settings." International Review of Psychiatry 31(3): 210-228.
	Perinatal depression is common and can have deleterious effects on mothers, infants, children, partners, and families. Despite this, few women who screen positive for depression receive psychiatric treatment. A comprehensive perinatal depression care pathway includes: (1) screening, (2) assessment, (3) triage and referral, (4) treatment access, (5) treatment initiation, (6) symptom monitoring, and (7) adaptation of treatment based on measurement until symptoms remit. This depression care pathway provides a scaffold on which to frame the challenges encountered when, and the opportunities that exist for, addressing depression in obstetric settings. Comprehensive interventions that address each step on the care pathway are needed to support obstetric practices in providing high-quality, evidence-based, effective treatment including pro-active follow-up for depression management. Despite recent attention being brought to, and significant progress in the field of maternal mental health, gaps in care persist. Ultimately, depression care needs to be fully integrated into obstetric care. Additionally, more targeted maternal mental health support and structure are needed for integration to occur and ultimately be optimized. Specific areas requiring more attention include consistency of screening, evaluation of patients with a positive depression screen for bipolar disorder, anxiety or substance use disorders, and monitoring of symptom improvement.Copyright © 2019, © 2019 Institute of Psychiatry and Johns Hopkins University.

Cabanas-Barja, A., et al. (2024). "Update on physiotherapy treatment in endometriosis: A systematic review." Clinica e Investigacion en Ginecologia y Obstetricia 51(1): 100929.
	Endometriosis is a chronic, inflammatory gynecological pathology characterized by the presence of endometrial tissue outside the uterus. Clinical manifestations include chronic pelvic pain, fatigue, dysmenorrhea, dyspareunia, infertility, dysuria and dyschezia. Physical therapy can be part of the symptomatic treatment of endometriosis; therefore, this review aims to analyze the scientific literature to evaluate the effect of physical therapy in endometriosis. A bibliographic search was carried out during the first two weeks of December 2022 in the databases PubMed, Medline, Scopus, Web of Science, PEDro, CINAHL and ENFISPO. The descriptors "Endometriosis" "Physical Therapy Modalities", "Physiotherapy", "Physiotherapist", "Physical therapy" and "Physical rehabilitation" were used. Results were limited to randomized clinical studies published in English or Spanish. A total of 943 results were obtained, of which 6 were selected after applying the eligibility criteria. The selected studies develop different physiotherapy interventions with techniques such as electrotherapy with TENS and high intensity pulsed laser, progressive muscle relaxation training, aerobic training, manual therapy, and therapeutic exercise through yoga. Physiotherapy appears to provide benefits in terms of reducing pelvic pain and improving quality of life in women with endometriosis.Copyright © 2023 Elsevier Espana, S.L.U.

Cacciamani Giovanni, E., et al. (2023). "Assessment and Reporting of Perioperative Adverse Events and Complications in Patients Undergoing Inguinal Lymphadenectomy for Melanoma, Vulvar Cancer, and Penile Cancer: A Systematic Review and Meta-analysis." World journal of surgery 47(4): 962-974.
	Background: Inguinal lymph node dissection (ILND) plays a crucial role in the oncological management of patients with melanoma, penile, and vulvar cancer. This study aims to systematically evaluate perioperative adverse events (AEs) in patients undergoing ILND and its reporting.; Methods: A systematic review was conducted according to PRISMA. PubMed, MEDLINE, Scopus, and Embase were queried to identify studies discussing perioperative AEs in patients with melanoma, penile, and vulvar cancer following ILND.; Results: Our search generated 3.469 publications, with 296 studies meeting the inclusion criteria. Details of 14.421 patients were analyzed. Of these studies, 58 (19.5%) described intraoperative AEs (iAEs) as an outcome of interest. Overall, 68 (2.9%) patients reported at least one iAE. Postoperative AEs were reported in 278 studies, combining data on 10.898 patients. Overall, 5.748 (52.7%) patients documented ≥1 postoperative AEs. The most reported ILND-related AEs were lymphatic AEs, with a total of 4.055 (38.8%) events. The pooled meta-analysis confirmed that high BMI (RR 1.09; p = 0.006), ≥1 comorbidities (RR 1.79; p = 0.01), and diabetes (RR 1.81; p = < 0.00001) are independent predictors for any AEs after ILND. When assessing the quality of the AEs reporting, we found 25% of studies reported at least 50% of the required criteria.; Conclusion: ILND performed in melanoma, penile, and vulvar cancer patients is a morbid procedure. The quality of the AEs reporting is suboptimal. A more standardized AEs reporting system is needed to produce comparable data across studies for furthering the development of strategies to decrease AEs. (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Cacciari, L. P., et al. (2019). "Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women: a cochrane systematic review abridged republication." Brazilian journal of physical therapy 23(2): 93-107.
	BACKGROUND: Pelvic floor muscle training is the most commonly used physical therapy treatment for women with urinary incontinence. OBJECTIVE(S): To assess the effects of Pelvic floor muscle training for women with urinary incontinence in comparison to a control treatment and to summarize relevant economic findings. METHOD(S): Cochrane Incontinence Group Specialized Register (February 12, 2018). SELECTION CRITERIA: Randomized or quasi-randomized trials in women with stress, urgency or mixed urinary incontinence (symptoms, signs, or urodynamic). DATA COLLECTION AND ANALYSIS: Trials were independently assessed by at least two reviewers authors and subgrouped by urinary incontinence type. Quality of evidence was assessed by adopting the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULT(S): The review included thirty-one trials involving 1817 women from 14 countries. Overall, trials were small to moderate size, and many were at moderate risk of bias. There was considerable variation in the intervention's content and duration. Based on data available, we can be confident that Pelvic floor muscle training can cure or improve symptoms of stress and all other types of urinary incontinence. It may reduce the number of leakage episodes and the quantity of leakage, while improving reported symptoms and quality of life. Women were more satisfied with Pelvic floor muscle training, while those in control groups were more likely to seek further treatment. Long-term effectiveness and cost-effectiveness of Pelvic floor muscle training needs to be further researched. CONCLUSION(S): The addition of ten new trials did not change the essential findings of the earlier review, suggesting that Pelvic floor muscle training could be included in first-line conservative management of women with urinary incontinence.Copyright © 2019 Associacao Brasileira de Pesquisa e Pos-Graduacao em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Cacciari, L. P., et al. (2021). "Pelvic floor morphometrical and functional changes immediately after pelvic floor muscle training and at 1-year follow-up, in older incontinent women." Neurourology and Urodynamics 40(1): 245-255.
	AIMS: To compare the effects of group-based and individual physiotherapy for stress or mixed urinary incontinence (UI) on pelvic floor morphometry, pelvic floor muscle (PFM) function, and related self-efficacy, immediately after treatment and at 1 year. METHODS: This is a planned secondary analysis of the group rehabilitation or individual physiotherapy study, an assessor-blinded, randomized, noninferiority trial. Eligible participants included 362 community-dwelling older women with symptoms of stress/mixed UI. After learning how to contract PFMs, participants completed 12 weeks of PFM training, either individually (one-on-one) or as part of a group (eight women). Pelvic floor transperineal ultrasound volumes (morphometry), PFM intravaginal dynamometric data (function), and self-efficacy in performing PFM exercises were acquired at baseline, posttreatment, and at 1 year. RESULTS: Groups were comparable at all time points. Immediately posttreatment, both groups demonstrated significant changes in pelvic floor morphometry during coughs, and in PFM function during contractions and coughs. Participants also reported improved self-efficacy in performing PFM exercises. Results were sustained at 1 year. When participants coughed, pelvic floor structures were better supported (reflected by less caudal movement of the puborectalis sling and a smaller opening of the levator hiatus) in a pattern consistent with the "knack" strategy. Furthermore, both interventions resulted in stronger, faster, more coordinated, and more endurant PFMs. CONCLUSION: In older women with stress or mixed UI, both individual and group-based PFM training resulted in comparable improvements in overall PFM function, pelvic floor morphometry during coughs, and related self-efficacy in performing PFM exercises, which were sustained at 1 year.

Cadish, L. A., et al. (2023). "Projecting future prolapse outcomes with induction of labor at 39 weeks: a decision analysis." International Urogynecology Journal.
	Introduction and hypothesis: In 2018, the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) concluded that routine induction of labor (IOL) at 39 weeks gestation decreases cesarean delivery risk, with slightly lighter birthweight infants. We debated whether routine IOL would improve, worsen, or not change POP risk compared with expectant management (EM). Methods: We constructed a decision analysis model with a lifetime horizon where nulliparous women reaching 39 weeks underwent IOL or EM. Subsequent vaginal versus cesarean delivery varied based on prior deliveries for up to four births. Subsequent delivery prior to 39 weeks and distribution of gestational age, birthweight, and delivery mode between 24 and 39 weeks was modeled from national data. We modeled increased POP risk with increasing vaginal parity, forceps delivery, and weight of largest infant delivered vaginally, accounting for differential infant weights in each strategy. Results: IOL and EM have similar population‐wide POP risk (15.9% and 15.7% respectively). Among women with only spontaneous vaginal deliveries that reached 39 weeks or beyond, the prevalence of POP was 20% after one delivery and 29% after four deliveries, with no difference between groups. The cesarean rate was lower with IOL (27.8% versus 29.8%). Sensitivity analysis revealed no meaningful thresholds among the variables, supporting model robustness. Conclusion: While routine induction of labor at 39 weeks results in a meaningfully higher vaginal delivery rate, there was no increase in POP, possibly due to the protective effect of lower birthweight.

Cadman, T., et al. (2024). "Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts." Environment international 185: 108453.
	Background: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD).; Objectives: We investigated associations between urban environment exposures during pregnancy and PPD.; Methods: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686-30,716 depending on exposure; representing 26-46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO 2 ) and particulate matter (PM 2.5 and PM 10 ), road traffic noise (L den ), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3-18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD.; Results: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM 10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM 10 ) whilst associations for exposure to NO 2 and PM 2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results.; Discussion: The study findings suggest that exposure to PM 10, road traffic noise and blue spaces in pregnancy may increase PPD risk, however future studies should explore this causally.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cadoo, K., et al. (2021). "Olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: secondary safety results from the phase II LIGHT study." Gynecologic Oncology 162(Supplement 1): S67-S68.
	Objectives: LIGHT (NCT02983799) evaluated olaparib treatment in patients with platinum-sensitive relapsed (PSR) ovarian cancer by BRCA mutation (BRCAm) and homologous recombination repair deficiency (HRD) status; the primary analysis demonstrated objective response rates (ORRs) of 69%, 64%, 29%, and 10% in cohorts of patients with a germline (g) BRCAm, with tumors with somatic (s) BRCAm, HRD-positive (non-BRCAm), and HRD-negative status, respectively (Cadoo K et al. ASCO 2020). Here, we report pre-specified secondary efficacy endpoints and subgroup analyses. Method(s): In this open-label, non-randomized study, patients with PSR ovarian cancer and >=1 prior line of platinum-based chemotherapy received olaparib monotherapy (300 mg bid). Patients were assigned to one of four cohorts based on whether they had a gBRCAm, tumors with sBRCAm, had HRD-positive (non-BRCAm) tumors, or HRD-negative tumors. Testing for gBRCAm was completed using Myriad BRACAnalysis CDx; sBRCAm testing was done with Myriad myChoice CDx. Genomic instability (GI) was assessed using the Myriad myChoice HRD test; tumors were deemed HRD-positive if they had a GI score >=42. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS; RECIST v1.1) and cancer antigen (CA)-125 response. Time to any progression (TTAP) was calculated from the date of the first dose of olaparib until the earliest date of RECIST v1.1 or CA-125 disease progression, or death. Result(s): The analysis was timed ~6 months after the last patient was enrolled (data cut-off, Aug 27, 2019). Of 271 enrolled patients who had received olaparib, 270 had measurable disease at baseline and were included in efficacy analyses (13 patients whose Myriad test result was failed or missing could not be assigned to a cohort; efficacy in these patients was analyzed separately). ORR and PFS by prior line of chemotherapy, CA-125 response, and TTAP are summarized in the Table. ORRs ~60-70% were observed in the gBRCAm and sBRCAm cohorts and ~30% in the HRD-positive (non-BRCAm) cohort, both in patients with 1 or >=2 prior lines of chemotherapy. Similarly, median PFS in patients was ~10-11 months in the BRCAm cohorts, and ~5-7 months in the HRD-positive (non-BRCAm) cohort, both in patients with 1 or >=2 prior lines of chemotherapy. In the BRCAm cohorts, a high proportion of patients achieved a CA-125 response and complete response (CR), with a CA-125 CR rate of 60% and 68% in the BRCAm cohorts and 29% in the HRD-positive non-BRCAm cohort. Median TTAP was ~11 months in the BRCAm cohorts, and 7.2 months in the HRD-positive (non-BRCAm) cohort.[Formula presented] Conclusion(s): Secondary efficacy data and subgroup analyses from the LIGHT study of olaparib monotherapy as treatment for PSR ovarian cancer support the primary analysis. Efficacy was observed in all cohorts, particularly in the gBRCAm and sBRCAm cohorts, where similar efficacy was observed. For patients without a BRCAm, greater efficacy was seen in the HRD-positive cohort.Copyright © 2021 Elsevier Inc.

Cadoo, K., et al. (2022). "Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis." Gynecologic Oncology 166(3): 425-431.
	Objective: Olaparib treatment resulted in significant improvement in objective response rates (ORRs) and progression-free survival (PFS) over non‑platinum chemotherapy in patients with BRCA1/BRCA2-mutated (BRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) and ≥2 prior lines of platinum-based chemotherapy in the phase III SOLO3 study. LIGHT (NCT02983799) prospectively evaluated olaparib treatment for patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status.; Methods: In this phase II open-label multicenter study, patients with PSROC and ≥1 prior line of platinum-based chemotherapy were assigned to cohorts by presence of germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive tumors without BRCAm, or HRD-negative tumors. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR) and PFS. Tumors were analyzed using Myriad BRACAnalysis CDx and myChoice HRD assays; HRD-positive tumors were defined using a genomic instability score of ≥42.; Results: Of 272 enrolled patients, 271 received olaparib and 270 were included in efficacy analyses. At data cut-off, ORRs in the gBRCAm, sBRCAm, HRD-positive, and HRD-negative cohorts were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. DCRs were 96.0%, 100.0%, 79.4%, and 75.3% in each cohort, respectively. Median PFS was 11.0, 10.8, 7.2, and 5.4 months, respectively. The most common (≥ 20%) treatment-emergent adverse events included nausea, fatigue/asthenia, vomiting, anemia, constipation, diarrhea, and decreased appetite.; Conclusions: Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cagliari University, o., et al. (2021). Evaluation of Ovarian Reserve and Recurrence Rate After DWLS Diode Laser OMA Vaporization.
	No Results Available Procedure: laparoscopic endometrioma laser vaporization Evaluation of the ovarian reserve using AntiMullerian Hormone (AMH) assessment.|Evaluation of the ovarian reserve using Antral follicular Count (AFC)|Evaluation of the patients' symptoms|Evaluation of endometrioma recurrence rate|Evaluation of pregnancy rate Female Not Applicable 70 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment OMA Diode Laser Vaporization September 1, 2023

Cagnacci, A., et al. (2022). "Polycarbophil vaginal moisturizing gel versus hyaluronic acid gel in women affected by vaginal dryness in late menopausal transition: A prospective randomized trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 270: 239-245.
	Objectives: During menopausal transition, women are frequently affected by vulvovaginal atrophy (VVA), due to the decline of estrogen levels. Resulting symptoms are itching, burning, dyspareunia, and vaginal dryness (reported in up to 85%). The aim of this trial was to verify if medical device polycarbophil vaginal (PCV) moisturizer gel is not less effective than hyaluronic acid (HA) gel in treating vaginal dryness.; Material and Methods: This was a multicenter, open label, randomized, parallel group, comparative study with non-inferiority design. Female included were ≥45 to ≤55 years in the menopausal transition, with subjective dryness, any objective sign of VVA, pH > 5, and body mass index of ≥18.5 to ≤36 kg/m 2 . Subjects were randomized to 1 g of PCV gel twice a week for 30 days or 3 g of HA vaginal gel every 3 days for 30 days.; Results: 53 subjects (mean age 49.45 ± 2.96 years) were analyzed. Vaginal health index showed an improvement (p < 0.001) in both groups (from 12.54 ± 1.37 to 16.36 ± 2.66 for PCV, from 12.00 ± 1.91 to 16.60 ± 2.50 for HA), but the difference between final means (95%CI: -1.66 to 1.18) evidenced that PCV is non-inferior to HA treatment. Similarly, an improvement was evidenced in vaginal maturation index (p = 0.005 for PCV, ns. for HA), female sexual function index (p < 0.001 for PCV, p < 0.001 for HA), and SF-12 (p < 0.001 for PCV, p < 0.001 for HA), with no difference between groups. Safety was optimal and no adverse events were reported.; Conclusions: The use of HA gel does not give additional benefits to those that are already provided by the moisturizing PCV. (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cai, P. (2021). "Discussion on the Value of Mifepristone and Misoprostol in the Treatment of Missed Abortion." 中外医学研究 19(26): 100‐102.
	Objective: To study the effect of mifepristone + misoprostol in patients with missed abortion. Methods: The samples were collected from 150 missed abortion patients admitted to the obstetrics and gynecology clinic and ward from January 2018 to December 2019. They were divided into the control group (direct uterine removal, n=75) and the observation group (mifediline) by random number table. ketone + misoprostol, n=75), and the two groups were compared in terms of clinical indicators, complications of uterine clearance, clinical efficacy and adverse reactions. Results: There was no significant difference in adverse reactions between the two groups (P>0.05); after treatment, compared with the control group, the observation group had shorter vaginal bleeding, menstrual rehydration time, less vaginal bleeding, and the observation group had a total effective rate ( 97.33%) was higher than that in the control group (86.67%), and the complication rate in the observation group (2.67%) was lower than that in the control group (16.00%), with a statistically significant difference (P<0.05). Conclusion: Combination medication in the treatment of missed abortion can improve the curative effect, reduce the occurrence of adverse reactions, and promote the recovery of the body, which is worthy of reference.

Cai, T., et al. (2022). "The efficacy and tolerability of pollen extract in combination with hyaluronic acid and vitamins in the management of patients affected by chronic prostatitis/chronic pelvic pain syndrome: a 26 weeks, randomized, controlled, single-blinded, phase III study." Minerva urology and nephrology 74(6): 780-788.
	Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains a challenging clinical condition to manage. Here, we evaluate the efficacy and tolerability of a new treatment option (suppositories) containing pollen extract in combination with hyaluronic acid and vitamins in the management of patients with CP/CPPS.; Methods: In this prospective, randomized, controlled, single-blinded, phase-III study we enrolled CP/CPPS patients between March and December 2019. Participants were randomized (1:1) to the following treatment groups: 1) pollen extract suppositories 1 daily for 10 days; or 2) ibuprofen 600 mg 1 tablet in the morning for 10 days. At the enrolment time and at the follow-up evaluations (3, 6 months), all patients completed baseline questionnaires ([National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] and Quality of Well-Being [QoL]) and underwent urological examination and microbiological evaluation. The primary endpoint was the quality-of-life assessment with Patients' Reported Outcomes (PROs).; Results: One hundred and eighty-seven patients were screened. Finally, one hundred and twenty-four patients (mean age 34.6±3.9 years) were randomly allocated to the new pollen extract treatment (N.=63) or ibuprofen (N.=61) groups. At the end of follow-up examinations 56/63 group 1 patients (88.8%) showed a significant reduction of the NIH-CPSI total score, compared with 17/61 (27.8%) in group 2 (P<0.0001). Group 1 patients also reported a higher improvement in terms of PROs, when compared with the control group and group 1 patients reported a significant reduction of leucocyte count at the Meares-Stamey Test (-12; -4; P<0.001). Only mild adverse events were reported in the two groups and adverse events were less frequent in the pollen extract suppositories group.; Conclusions: The combination of pollen extract with hyaluronic acid and vitamins is more effective than ibuprofen in improving symptoms and Quality of Life in patients affected with CP/CPPS and has less side effects.

Caike Costa, F., et al. (2021). "Evaluation of transdermal testosterone use in postmenopause women with hypoactive sexual desire: A systematic Review."
	
Caiyun, W., et al. (2021). "Comparative efficacies of different immunotherapy regimens in recurrent implantation failures: A systematic review and network meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Calabrio Marcela, M., et al. (2019). "Transcutaneous nervous electric stimulation (TENS) in the treatment of localized provoked vulvodynia: systematic review." Femina 47(5): 302-306.
	
Calaf-Alsina, J., et al. (2023). "Sequential management of postmenopausal health and osteoporosis: An update." Maturitas 177: 107846.
	Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.Copyright © 2023

Caldwell, P. H. Y., et al. (2022). "An Alarm Watch for Daytime Urinary Incontinence: A Randomized Controlled Trial." Pediatrics 149(1): e2021053863.
	OBJECTIVES: Daytime urinary incontinence is disabling and occurs in 17% of school-aged children. Timed-voiding is part of standard therapy. Can an alarm watch to aid timed-voiding improve treatment response to standard therapy? METHODS: The WATCH (Watch with Alarm for Timed-Voiding in Children) study is a randomized controlled trial. Participants were randomly assigned (1:1) to a vibrating alarm or nonalarming watch for 3-months. The primary outcome was the proportion who achieved a complete response (14 consecutive dry days) after 3-months of treatment. Children aged 5 to 13 years who were prescribed timed-voiding for daytime urinary incontinence. RESULT(S): Overall, 243 children, with a mean age of 8 years, were enrolled, with 62% girls. At 3-months, the complete response rates were similar between the 2 groups (22% alarm versus 17% control; difference: 5%; 95% confidence interval (CI): 5% to 16%; P 5 .42). In the alarm group, treatment adherence was higher (40% vs 10%; difference: 30%; 95% CI: 20% to 40%; P < .001), frequency of incontinence was lower (25% dry; 40% had 1-3 wet days per week, 24% had 4-6 wet days per week, and 12% had daily wetting, compared with 19%, 30%, 35%, and 16%, respectively; P 5.05), and fewer had abnormal postvoid residual urine volumes (12% vs 24%; difference: 12%; 95% CI: 21% to 1%; P 5 .04) compared with the control group. Improvement was transient and did not persist 6 months beyond the treatment period. CONCLUSION(S): Alarm watches do not appear to lead to complete resolution of urinary incontinence in children but did promote treatment adherence, normalization of postvoid residual volumes, and reduction in incontinent episodes while being used.Copyright © 2022 by the American Academy of Pediatrics.

Calero Maria, J., et al. (2022). "Fertility and Pregnancy Outcomes in Patients With Adenomyosis: Is Adenomyosis Synonymous With Infertility?" Cureus 14(10): e30310.
	Adenomyosis is a disease related to the presence of endometrial glands and stromal cells within the uterine myometrium that used to be linked to females that are more than 40 years old and multiparous. Nowadays, females are delaying their pregnancies to their third or fourth decade, and as diagnostic approaches evolve, the disease has become a common problem for females who desire pregnancy. The aim of this study is to identify the physio-pathological factors by which adenomyosis causes infertility and pregnancy complications, as well as the possible results from infertility treatments and the most common pregnancy complications that females with adenomyosis face. A systematic review based on a systematic search from PubMed, Cochrane, and ScienceDirect databases from the past five years was done. Papers with free full text available were subject to the removal of duplicates, screening for relevant titles and abstracts, and a quality assessment to identify the risk of bias (RoB). A total of 10 papers were selected for this study; they include systematic reviews and meta-analyses, cohorts, literature review, and a case-control study. After the review of the data, we conclude that infertility may be due to several factors that impair adequate sperm mobility through the uterus and an impaired implantation of a product. After some fertility treatments were performed, females with adenomyosis had a lower rate of clinical pregnancy. The pregnancy complications such as preterm delivery and hypertension problems related to pregnancy had an increased risk for females with adenomyosis, while for others such as intrauterine fetal death and gestational diabetes, the information is still controversial. The main limitation of this study was the lack of information of physio-pathological-related information probably due to only including data from the past five years.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Calero et al.)

Calgary University, o., et al. (2022). Postoperative Return to Sexual Activity.
	No Results Available Other: Structured Counselling Tool Preparedness to return to sexual activity|Sexual Function|Postoperative Pain|Time to Return to Sexual Function Female Not Applicable 170 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Supportive Care 21-0749 November 2023

Callen, E., et al. (2023). "EE264 Immunotherapy for Advanced and Recurrent dMMR Endometrial Cancer: A Cost-Effectiveness Analysis." Value in Health 26(6 Supplement): S107.
	Objectives: Few treatment options exist for patients with advanced or recurrent endometrial cancer (EC) that has progressed after treatment with platinum-based therapy. Dostarlimab and pembrolizumab are approved for patients with advanced cancers that have not responded to prior therapy and are mismatch repair deficient (dMMR). This analysis aimed to add to the evidence on the cost-effectiveness of immunotherapy for advanced or recurrent dMMR EC. Method(s): Immunotherapy was compared to usual care (pegylated doxorubicin, PLD). A partitioned survival model was used to estimate probabilities of progression free survival, overall survival and death over a 25-year time horizon. Probabilities of being in each state were derived from survival curves in the published literature. Costs and utilities were derived from published literature and government estimates and discounted at 3 percent annually. Per-cycle costs of PLD, pembrolizumab, and dostarlimab were $1,680, $10,910, and $11,038, respectively. Model outputs were life-years gained, quality-adjusted life-years (QALYs) gained, costs, and incremental cost effectiveness ratios (ICERs). One-way sensitivity analysis was conducted to assess the impact of parameter uncertainties on modeled outcomes. Result(s): Compared to PLD, pembrolizumab resulted in 3.18 life-years and 2.20 QALYs gained, with an incremental cost of $612,125 and an ICER of $278,123 per QALY gained. Pembrolizumab was subject to extended dominance by dostarlimab, which yielded a gain of 3.84 life-years and 2.62 QALYs, with an incremental cost of $703,819 ($268,910 per QALY gained). Results were sensitive to cycles of therapy needed to attain maximum clinical benefit and per-cycle cost of progressed disease. Conclusion(s): Dostarlimab and pembrolizumab led to increases in life expectancy and quality of life compared to PLD, but these results suggest they may not currently be priced in line with expected clinical benefit at a willingness-to-pay threshold of $150,000/QALY. More work is needed to understand clinical trajectories following treatment with immunotherapy and cycles needed to attain maximum benefit.Copyright © 2023

Callens, C., et al. (2023). "Shallow whole genome sequencing approach to detect Homologous Recombination Deficiency in the PAOLA-1/ENGOT-OV25 phase-III trial." Oncogene 42(48): 3556-3563.
	The bevacizumab (bev)/olaparib (ola) maintenance regimen was approved for BRCA1/2-mutated (BRCAmut) and Homologous Recombination Deficient (HRD) high-grade Advanced Ovarian Cancer (AOC) first line setting, based on a significantly improved progression-free survival (PFS) compared to bev alone in the PAOLA-1/ENGOT-ov25 trial (NCT02477644), where HRD was detected by MyChoice CDx PLUS test. The academic shallowHRDv2 test was developed based on shallow whole-genome sequencing as an alternative to MyChoice. Analytical and clinical validities of shallowHRDv2 as compared to MyChoice on 449 PAOLA-1 tumor samples are presented. The overall agreement between shallowHRDv2 and MyChoice was 94% (369/394). Less non-contributive tests were observed with shallowHRDv2 (15/449; 3%) than with MyChoice (51/449; 11%). Patients with HRD tumors according to shallowHRDv2 (including BRCAmut) showed a significantly prolonged PFS with bev+ola versus bev (median PFS: 65.7 versus 20.3 months, hazard ratio (HR): 0.36 [95% CI: 0.24-0.53]). This benefit was significant also for BRCA1/2 wild-type tumors (40.8 versus 19.5 months, HR: 0.45 [95% CI: 0.26-0.76]). ShallowHRDv2 is a performant, clinically validated, and cost-effective test for HRD detection.Copyright © 2023, The Author(s).

Callens, C., et al. (2021). "Concordance Between Tumor and Germline BRCA Status in High-Grade Ovarian Carcinoma Patients in the Phase III PAOLA-1/ENGOT-ov25 Trial." Journal of the National Cancer Institute 113(7): 917‐923.
	BACKGROUND: PAOLA1 is a phase III study assessing olaparib maintenance therapy in advanced high‐grade ovarian carcinoma patients responding to first‐line platinum‐taxane‐based chemotherapy plus bevacizumab as standard of care. Randomization was stratified by treatment outcome and tumor BRCA1/2 status (tBRCA) at screening. METHODS: tBRCA was tested on formalin‐fixed, paraffin‐embedded tumor blocks on 5 French platforms using 2 next‐generation sequencing methods based either on hybrid capture or amplicon technology. One of the exploratory objectives was to assess the concordance between germline (gBRCA) and tBRCA testing in French patients. gBRCA testing was performed on blood samples on the same platforms. RESULTS: From May 2015 to July 2017, tBRCA tests were performed for 1176 screened patients. Only 52 (4.4%) tumor samples were noncontributive. The median interval between reception of the tumor sample and availability of the tBRCA status result was 37 days (range = 8‐260). A pathogenic variant was reported in 27.1% tumor samples (319 of 1176 screened patients). tBRCA and gBRCA testing were performed for 451 French patients with negative results for both tests in 306 patients (67.8%) and positive results for both tests in 85 patients (18.8%). Only 1 large genomic rearrangement of BRCA1 was detected, exclusively in the blood sample. Interestingly, tBRCA testing revealed 6.4% of pathogenic variant (29 of 451) not detected by gBRCA testing. CONCLUSIONS: tBRCA testing is an appropriate tool with an acceptable turnaround time for clinical practice and a low failure rate, ensuring reliable identification of patients likely to benefit from poly(ADP‐ribose) polymerase inhibitor therapy.

Calles, S., et al. (2023). "Complications of Pessaries Amenable to Surgical Correction: Two Case Reports and a Systematic Review of the Literature." Journal of Personalized Medicine 13(7).
	Background: Forty percent of women will experience prolapse in their lifetime. Vaginal pessaries are considered the first line of treatment in selected patients. Major complications of vaginal pessaries rarely occur.; Methods: PubMed and Embase were searched from 1961 to 2022 for major complications of vaginal pessaries using Medical Subject Headings (MeSH) and free-text terms. The keywords were pessary or pessaries and: vaginal discharge, incontinence, entrapment, urinary infections, fistula, complications, and vaginal infection. The exclusion criteria were other languages than English, pregnancy, complications without a prior history of pessary placement, pessaries unregistered for clinical practice (herbal pessaries), or male patients. The extracted data included symptoms, findings upon examination, infection, type of complication, extragenital symptoms, and treatment.; Results: We identified 1874 abstracts and full text articles; 54 were assessed for eligibility and 49 met the inclusion criteria. These 49 studies included data from 66 patients with pessary complications amenable to surgical correction. Clavien-Dindo classification was used to grade the complications. Most patients presented with vaginal symptoms such as bleeding, discharge, or ulceration. The most frequent complications were pessary incarceration and fistulas. Surgical treatment included removal of the pessary under local or general anesthesia, fistula repair, hysterectomy and vaginal repair, and the management of bleeding.; Conclusions: Pessaries are a reasonable and durable treatment for pelvic organ prolapse. Complications are rare. Routine follow-ups are necessary. The ideal patient candidate must be able to remove and reintroduce their pessary on a regular basis; if not, this must be performed by a healthcare worker at regular intervals.

Calvo, E., et al. (2022). "Phase I study of lurbinectedin in combination with weekly paclitaxel with or without bevacizumab in patients with advanced solid tumors." Investigational New Drugs 40(6): 1263-1273.
	Lurbinectedin and paclitaxel showed synergism in preclinical studies and have non-completely overlapping toxicity profiles. This phase I trial evaluated a combination of paclitaxel and lurbinectedin with/without bevacizumab in advanced tumors. This trial was divided into Group A, which evaluated weekly paclitaxel (60 or 80 mg) plus lurbinectedin (3.0-5.0 mg flat dose [FD] or 2.2 mg/m 2 ) every 3 weeks in advanced solid tumors; and Group B, which evaluated bevacizumab (BEV, 15 mg/kg) added to the recommended dose (RD) defined in Group A in advanced epithelial ovarian or non-small cell lung cancer (NSCLC). 67 patients (A, n = 55; B, n = 12) were treated. The RD was paclitaxel 80 mg/m 2 on Day (D)1,D8 plus lurbinectedin 2.2 mg/m 2 on D1. At this RD, myelotoxicity was reversible and manageable, and most non-hematological toxicities were mild/moderate. Adding BEV did not notably change tolerability. Twenty-five confirmed responses were observed: 20/51 evaluable patients in Group A (overall response rate [ORR] = 39% at all dose levels and at the RD), and 5/10 evaluable patients in Group B (ORR = 50%). Most responders had breast (n = 7/12 patients), small cell lung (SCLC) (n = 5/7), epithelial ovarian (n = 3/9) and endometrial cancer (n = 3/11) in Group A, and epithelial ovarian (n = 3/4) and NSCLC (n = 2/6) in Group B. Clinical benefit rate was 61% in Group A (58% at the RD), and 90% in Group B. No major pharmacokinetic drug-drug interactions were observed. Paclitaxel/lurbinectedin and paclitaxel/lurbinectedin/BEV are feasible combinations. Further development is warranted of paclitaxel/lurbinectedin in SCLC, breast, and endometrial cancer, and of paclitaxel/lurbinectedin/BEV in epithelial ovarian cancer. (© 2022. The Author(s).)

Camela, E., et al. (2022). "Giant basal cell carcinoma of the vulva successfully treated with Sonidegib." Dermatologic therapy 35(9): e15723.
	
Camilo Fabio, M., et al. (2023). "The Effects of Electrode Placement on Analgesia Using Transcutaneous Electrical Nerve Stimulation for Primary Dysmenorrhea: A Single-Blind Randomized Controlled Clinical Trial." Cureus 15(5): e39326.
	Background Primary dysmenorrhea (PD) refers to the occurrence of painful menstrual cramps without pathological involvement of the pelvic organs, with considerable morbidity and high prevalence among females of reproductive age. Objective The objective of this study is to present and test the efficacy of an innovative method of interactive transcutaneous electrical nerve stimulation (iTENS) for PD. Methods and materials This study is a single-blind controlled clinical trial. This was conducted at the outpatient clinic of the faculty of physical therapy. Females with PD (n=124) were divided into the treated group (transcutaneous electrical nerve stimulation {TENS} group {TG}, n=62) and the placebo group (PG, n=62). A single session of either iTENS or placebo intervention was used for 35 minutes. Pain, the duration of analgesia, and the use of pain medication were assessed before and after the intervention. Data from before and after the treatment were compared between groups (Student's t-test). The level of significance was set at 5%. Results A significant decrease in pain (p<0.001) was observed after the intervention for the TG, with a more long-lasting analgesia (p<0.001) and decreased need for pain medication (p<0.001). Conclusions The proposed method of transcutaneous electrical nerve stimulation (TENS) application showed positive results for pain management on females with PD, with no reported adverse effects. The new proposed TENS application takes into account the preferences of the patient regarding positioning and the number of channels needed to cause analgesia. This application was able to promote almost complete analgesia in females with primary dysmenorrhea, and the analgesia persisted for more than one menstrual cycle.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Camilo et al.)

Campagna, G., et al. (2022). "Laparoscopic uterosacral ligament suspension: a comprehensive, systematic literature review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 277: 57-70.
	Objectives: Laparoscopic uterosacral ligament suspension (LUSLS) of the vaginal apex for the treatment of pelvic organ prolapse (POP) has gained popularity. The aim of this systematic review is to investigate perioperative outcomes and complications, subjective and objective success rates and recurrence rates in women undergoing this surgical procedure.; Study Design: A systematic literature search was performed in December 2021. The critical appraisal skills program (CASP) was used to assess the methodological quality of the selected studies. The Clavien-Dindo (CD) scale and the Satava scale were used to classify periprocedural complications. Continuous variables were described as means and standard deviations while categorical were expressed as percentages of the whole group. Statistical significance was set at p < 0.05.; Results: 26 articles were selected and analysed, with a total population of 1401 patients. Anatomical and subjective success rates after LUSLS ranged from 79% and 100% and from 76.2% to 100% respectively. The re-operation rate varied from 2% to 4.5% in the largest cohorts. The overall complication rate was 13.6%, however grade III CD complications occurred only in 1% of patients. Ureteral complications were described in only 2 cases.; Conclusions: LUSLS represent a safe and effective technique for vaginal apex resuspension in women with POP. Further larger prospective randomized studies are required to confirm these data.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Campagna, G., et al. (2023). "Clinical, anatomical and perioperative outcomes of abdominal sacral colpopexy using autologous fascia: A systematic review of the literature." Journal of Gynecology Obstetrics and Human Reproduction 52(8): 102635.
	Objectives: Although sacral colpopexy is considered the gold standard for the treatment of advanced apical prolapse, several warnings and restrictions has been delivered to urogynecological surgeons in order to avoid the implants of prosthetics meshes. The purpose of this systematic review is to investigate the role of sacral colpopexy performed with autologous tissue in literature.; Methods: a systematic review according to PRISMA guidelines was performed in June 2022 through the Medline, Web of Science and Scopus databases. Quality assessment of each article was performed according to Critical Appraisal tool of Oxford center for EBM, LoE according to SORT standards, ROBINS-I tool for methodological assessment in non-randomized trials. From 236 screened records, 7 articles were considered eligible for this systematic review.; Results: Collected data showed objective cure rate ranging from 94.7% to 100% in medium term follow up. Subjective cure rate was specifically investigated in 2 studies with high satisfaction rates. Complication rate ranged from 0 to 36.8%, with 90.1% graded ≤2 according to Clavien-Dindo classification.; Conclusions: sacral colpopexy with autologous fascia shows satisfying outcomes in terms of safety and efficacy and may be taken in account in particular clinical situations.; Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Campagna, G., et al. (2021). "Laparoscopic lateral suspension for pelvic organ prolapse: A systematic literature review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 264: 318-329.
	Background: Abdominal lateral suspension with mesh represents an alternative treatment to suspend the vaginal apex.; Objectives: The aim of this study was to summarize literature data regarding the anatomical and functional outcomes, and intra- and postoperative complications of this technique with minimally invasive approach (laparoscopic/robotic).; Search Strategy: Systematic literature search using MEDLINE/PubMed, SCOPUS, Web of Science.; Data Collection and Analysis: Two authors extracted data on baseline characteristics (age, BMI, prior pelvic reconstructive surgery, preoperative POP stage), perioperative outcomes (operative time, estimated blood loss, intraoperative and postoperative complications, admission time), objective and subjective success rate, surgical failure, time of follow-up. Data were presented descriptively.; Main Results: Thirteen studies were included in the review. The overall number of patients for our analysis was 1066. Patients referred for laparoscopic/robotic lateral suspension were most frequently postmenopausal, aged 50 to 65 years, BMI ≥ 25 kg/m2; 22.2% were already hysterectomized, while 17% had already a previous POP surgery. Operative time ranged from 78.4 ± 29.7 to 254 ± 45 min. The overall anatomic success was more than 90% in the apical compartment and more than 88% in the anterior compartment. Subjective cure rate varies from 78.4% to 100% in medium-term follow-up. Post-operative complication grade >= 3 according to Claiven-Dindo Scale was 1.03%. Mesh erosion rate varied between 0% and 13%.; Conclusions: Results coming from our systematic review suggest safety, efficacy and feasibility of minimally invasive lateral suspension with optimal anatomical and functional outcomes. Well-designed, randomized, controlled trials are required to confirm this data.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Campitelli, M., et al. (2021). "Brachytherapy or external beam radiotherapy as a boost in locally advanced cervical cancer: A Gynaecology Study Group in the Italian Association of Radiation and Clinical Oncology (AIRO) review." International Journal of Gynecological Cancer 31(9): 1278-1286.
	This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer, identifying whether radiation therapy modalities impact clinical outcomes with the ultimate aim of evaluating alternatives to brachytherapy. Three independent Italian radiation oncologists conducted a literature search on different external beam radiotherapy boost modalities in locally advanced cervical cancer. The search yielded 30 studies. Eight dosimetric studies, evaluating target coverage and dose to organs at risk, and nine clinical investigations, reporting clinical outcomes, were analyzed. Dosimetric studies comparing external beam radiotherapy boost with brachytherapy produced divergent results, while clinical studies were limited by their retrospective nature, heterogeneous doses, radiation schedules, volumes and techniques, diverse follow-up times, and small cohorts of patients. Evidence emerged that high-tech external beam radiotherapy seemed no better than image-guided brachytherapy for delivering a boost in locally advanced cervical cancer. Prospective clinical studies comparing high-tech external beam radiotherapy and image-guided brachytherapy should be encouraged.Copyright ©

Campos, L. S., et al. (2021). "Survival after Laparoscopic versus Abdominal Radical Hysterectomy in Early Cervical Cancer: A Randomized Controlled Trial." Asian Pacific journal of cancer prevention : APJCP 22(1): 93-97.
	BACKGROUND: Previous studies have reported the safety of laparoscopic radical hysterectomy for treatment of early cervical cancer, as option to laparotomy. This study aims to compare overall survival between laparoscopic versus abdominal radical hysterectomy for early cervical cancer. METHODS: A single-center randomized controlled trial enrolled 30 patients with clinically staged IA2 cervical cancer and lymphovascular invasion, IB and IIA, who underwent laparoscopic radical hysterectomy (16) or abdominal radical hysterectomy (14). RESULT: The mean overall survival time was 74.74 months (CI 95%: 54.15-95.33) for LRH 91.67 months (CI 95%: 74.97-108.37) for ARH (log-rank test = 0.30). The mean disease-free survival time was 81.07 months (CI 95%: 60.95-101.19) for LRH and 95.82 months (CI 95%: 80.18-111.47) for ARH (log-rank test = 0.371). The overall survival hazard ratio was 2.05 (CI 95%: 0.51-8.24), and the disease-free hazard ratio was 2.13 (CI 95%: 0.39-11.7). CONCLUSION: Our study suggests a non-significant trend of worse outcomes for LRH. In light of recent controversy and need for prospective studies, further studies in different populations are required for definite conclusions and until then, patients should be aware of risks and benefits, survival data and quality of life outcomes related to both surgical techniques.

Campos, S., et al. (2022). "A randomized phase II trial of bevacizumab vs. bevacizumab and erlotinib as first-line consolidation after carboplatin, paclitaxel, and bevacizumab in newly diagnosed patients with mullerian tumors." International Journal of Clinical Oncology 27(12): 1881-1890.
	Background: The combination of paclitaxel to platinum remains the backbone of therapy in patients with advanced Mullerian tumors. In patients with newly diagnosed Mullerian tumors, we investigated the progression-free survival benefit of bevacizumab and bevacizumab and erlotinib as consolidation therapy post-induction therapy. Method(s): Sixty patients were enrolled in a phase II trial of carboplatin, paclitaxel, and bevacizumab (induction therapy). After the completion induction therapy, patients were stratified by response (>= SD) and then randomized (1:1) to either bevacizumab (A) or bevacizumab and erlotinib (AE.) The primary endpoint was PFS. Secondary endpoints included the response rate of induction and consolidation therapy and toxicity profile of each consolidative arm. Each consolidative arm was compared to the historical control GOG 111. Result(s): Forty-eight patients advanced to the consolidative phase of the trial. Twelve patients were removed in the induction phase, the majority for toxicity. The most common toxicity (grade >= 3) was diarrhea (20%: arm AE; 0%: arm A). One patient in the AE arm had a fatal cardiac arrest deemed unrelated to the study treatment. No gastrointestinal perforations were reported. The median PFS in the AE and A arm was 18.9 months (p < 0.0001) and 13.3 months (p: ns), respectively. The overall rate of grade 3/4 toxicities in the AE arm was 72% and in the A arm 30%. Six patients remain free of disease 10 years after enrollment. Conclusion(s): Combinatorial consolidation therapy with AE was associated with an improved progression-free survival in patients with Mullerian tumors.Copyright © 2022, The Author(s) under exclusive licence to Japan Society of Clinical Oncology.

Cancanelli, L., et al. (2022). "Evaluation of maintenance treatment with PARP inhibitors in ovarian carcinoma patients responding to platinum therapy: Use of restricted mean survival time as an index of efficacy." International journal of clinical pharmacology and therapeutics 60(1): 32-35.
	Background: Maintenance therapy using poly (ADP-ribose) polymerase inhibitors (PARPIs) is an important therapeutic option in advanced ovarian cancer after platinum-based chemotherapy.; Materials and Methods: We evaluated randomized studies (n = 5) describing the effect of maintenance therapy with PARPIs; they were obtained mainly by searching PubMed. Patient data for the analysis were derived from progression-free survival curves. Restricted mean survival time (RMST) and 95% confidence interval were estimated for individual arms of each trial.; Results: The three PARPIs used (olaparib, niraparib, rucaparib) all showed a higher effectiveness than placebo. The gains in progression-free survival were 6 - 8 months.; Conclusion: Maintenance therapy studies provide evidence that olaparib, niraparib, rucaparib are effective treatments for advanced ovarian cancer.

Cancer Queensland Centre for, G. and o. Queensland The University (2021). Sentinel Node Biopsy in Endometrial Cancer.
	No Results Available Procedure: TH BSO with SNB Note: If participants (≤45 years of age) wish to retain their ovaries a BSO may be omitted.|Procedure: TH BSO without retroperitoneal node dissection Note: If participants (≤45 years of age) wish to retain their ovaries a BSO may be omitted. Stage 1: Return to usual activities|Stage 2: Disease Free Survival|Cost Effectiveness using QALYs using EuroQoL-5D (EQ-5D) Questionnaire|Cost Effectiveness measuring Intervention costs|Cost Effectiveness measuring GP and specialist consultations|Cost Effectiveness measuring radiology and imaging requirements|Cost Effectiveness measuring prescriptions and over the counter medicine requirements|Cost Effectiveness measuring community and health service requirements and days off work and informal care required by family and friends using a combination of the Health Services Questionnaire and clinical files|Cost Effectiveness: direct costs using a bottom-up approach by recording the volume of resource use in both groups of the trial, and then applying a unit cost to each component|Perioperative Outcomes: Adverse Events|Perioperative Outcomes: Length of Surgery|Perioperative Outcomes: Blood Loss during Surgery|Perioperative Outcomes: Blood Transfusion Requirements during Surgery|Perioperative Outcomes: Length of Hospital Stay|Health Related Quality of Life and Fear of Recurrence|Incidence of Lymphedema|Adjuvant Treatment Requirements|Value of Molecular Biomarkers|Overall Survival|Patterns of Recurrence - date and localization of 1st recurrence|Impact of body composition (sarcopenia) on surgical complications, recovery and overall survival|Impact of frailty on surgical complications, recovery and overall survival|Follow-Up Strategies Female Phase 3 760 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ENDO-3 January 2031

Candiani, M., et al. (2022). "Fertility Sparing Procedure using Carbon Dioxide Fiber Laser Vaporization of Ovarian Endometrioma." Journal of visualized experiments : JoVE(185).
	The surgical management of endometrioma is still a matter of debate. Cystectomy, which is recognized as the standard technique, seems to be associated with a potential reduction in the ovarian reserve due to the inadvertent removal and thermal damage of healthy ovarian tissue. New ablative techniques with reduced tissue penetration depth and less thermal spread to the surrounding parenchyma may represent a viable alternative to cystectomy. For these reasons, the aim of this manuscript is to demonstrate the ablation of the endometrioma capsule using a CO2 fiber laser technique and discuss the clinical outcomes. Once the cyst has been drained and washed, a biopsy is taken. After cyst eversion, vaporization of the inner surface of the cyst is performed using a CO2 fiber laser. The technique is simple and reproducible as even young surgeons without any surgical experience were more confident in performing laser CO2 vaporization instead of cystectomy. The positive effects of CO2 technology are reported in a randomized controlled trial, where the postoperative changes in the antral follicular count (AFC) and antimullerian hormone (AMH) levels were compared between patients who had their endometrioma excised (cystectomy) and those who had undergone endometrioma vaporization with CO2 laser. The patients treated with CO2 laser showed significantly increased AFC without a reduction in serum AMH levels as compared to the cystectomy group, in which both parameters were significantly reduced. The postoperative pregnancy rate was also assessed, and comparable pregnancy rates were found after both treatments. On the contrary, patients treated with the CO2 fiber laser technique had more favorable in-vitro fertilization (IVF) outcomes compared to cystectomy. In conclusion, the CO2 fiber laser technique may represent a viable alternative to cystectomy in the surgical treatment of endometrioma in terms of ovarian preservation, pregnancy rates, and IVF outcomes. Moreover, it has the advantage of being independent of the surgeon's skills and personal experience.

Canfield, S. M. and K. E. Canada (2023). "Systematic Review of Online Interventions to Reduce Perinatal Mood and Anxiety Disorders in Underserved Populations." Journal of Perinatal and Neonatal Nursing 37(1): 14-26.
	Background: Online health interventions increase access to care, are acceptable to end users and effective for treating mental and physical health disorders. However, less is known about interventions to prevent and treat perinatal mood and anxiety disorders (PMADs). This review synthesizes existing research on PMAD prevention and treatment by exploring the treatment modalities and efficacy of online interventions and examining the inclusion of underserved populations in PMAD research. Method(s): Using PRISMA guidelines, authors conducted a systematic review of peer-reviewed literature published between 2008 and 2018 on online interventions aimed to prevent or treat PMADs. The authors also assessed quality. Eligible articles included perinatal women participating in preventive studies or those aimed to reduce symptoms of PMADs and utilized a Web-based, Internet, or smartphone technology requiring an online component. This study excluded telephone-based interventions that required one-on-one conversations or individualized, text-based responses without a Web-based aspect. Result(s): The initial search yielded 511 articles, and the final analysis included 23 articles reporting on 22 interventions. Most studies used an experimental design. However, no study achieved an excellent or good quality rating. Psychoeducation and cognitive-behavioral therapies (CBTs) were most common. Several interventions using CBT strategies significantly decreased depression or anxiety. Four studies recruited and enrolled mainly people identifying as low-income or of a racial or ethnic minority group. Attrition was generally high across studies. Discussion(s): More research using rigorous study designs to test PMAD interventions across all perinatal times is needed. Future research needs to engage diverse populations purposefully.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Canlorbe, G., et al. (2021). "Fertility-Sparing Surgery for Ovarian Cancer." Journal of Clinical Medicine 10(18).
	(1) Background: although most patients with epithelial ovarian cancer (EOC) undergo radical surgery, patients with early-stage disease, borderline ovarian tumor (BOT) or a non-epithelial tumor could be offered fertility-sparing surgery (FSS) depending on histologic subtypes and prognostic factors. (2) Methods: we conducted a systematic review to assess the safety and fertility outcomes of FSS in the treatment of ovarian cancer. We queried the MEDLINE, PubMed, Cochrane Library, and Cochrane ("Cochrane Reviews") databases for articles published in English or French between 1985 and 15 January 2021. (3) Results: for patients with BOT, FSS should be offered to young women with a desire to conceive, even if peritoneal implants are discovered at the time of initial surgery. Women with mucinous BOT should undergo initial unilateral salpingo-oophorectomy, whereas cystectomy is an acceptable option for women with serous BOT. Assisted reproductive technology (ART) can be initiated in patients with stage I BOT if infertility persists after surgery. For patients with EOC, FSS should only be considered after staging for women with stage IA grade 1 (and probably 2, or low-grade in the current classification) serous, mucinous or endometrioid tumors. FSS could also be offered to patients with stage IC grade 1 (or low-grade) disease. For women with serous, mucinous or endometrioid high-grade stage IA or low-grade stage IC1 or IC2 EOC, bilateral salpingo-oophorectomy and uterine conservation could be offered to allow pregnancy by egg donation. Finally, FSS has a large role to play in patients with non- epithelial ovarian cancer, and particularly women with malignant ovarian germ cell tumors.

Canlorbe, G., et al. (2020). "Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Therapeutic Management of Early Stages." Gynecologie Obstetrique Fertilite et Senologie 48(3): 287-303.
	Objectives: To provide guidelines for clinical practice from the French College of Obstetrics and Gynecology (CNGOF), based on the best evidence available, concerning early stage borderline ovarian tumors (BOT). Method(s): Bibliographical search in French and English languages by consultation of Pubmed, Cochrane, Embase, and international databases. Result(s): Considering management of early stage BOT, if surgery is possible without a risk of tumor rupture, the laparoscopic approach is recommended compared to laparotomy (Grade C). In BOT, it is recommended to take all the measures to avoid tumor rupture, including the peroperative decision of laparoconversion (Grade C). In BOT, extraction of the surgical specimen using an endoscopic bag is recommended (Grade C). In case of early stage, uni or bilateral BOT, suspected in preoperative imaging in a postmenopausal patient, bilateral adnexectomy is recommended (Grade B). In cases of bilateral BOT and desire of fertility preservation, a bilateral cystectomy is recommended (Grade B). In case of mucinous BOT and desire of fertility preservation, it is recommended to perform a unilateral adnexectomy (Grade C). In case of endometrioid BOT and desire of fertility preservation, it is not possible to establish a recommendation of treatment choice between cystectomy and unilateral adnexectomy. In case of mucinous BOT at definitive histological analysis in a woman of childbearing age who had an initial cystectomy, surgical revision for unilateral adnexectomy is recommended (Grade C). In the case of serous BOT with definitive histological analysis in a woman of childbearing age who has had an initial cystectomy, it is not recommended to repeat surgery for adnexectomy in the absence of residual suspicious lesion during initial surgery and/or on postoperative imaging (referent ultrasound or pelvic MRI) (Grade C). An omentectomy is recommended for complete initial surgical staging when BOT is diagnosed on extemporaneous analysis or suspected on preoperative radiological elements (Grade B). There is no data in the literature to recommend the type of omentectomy to be performed. If restaging surgery is decided for a presumed early stage BOT, an omentectomy is recommended (Grade B). Multiple peritoneal biopsies are recommended for complete initial surgical staging when BOT is diagnosed on extemporaneous or suspected on preoperative radiological elements (Grade C). In case of restaging surgery for a presumed early stage BOT, exploration of the abdominal cavity should be complete and peritoneal biopsies should be performed on suspicious areas or systematically (Grade C). A primary peritoneal cytology is recommended in order to achieve complete initial surgical staging when BOT is suspected on preoperative radiological elements (Grade C). In case of restaging surgery for presumed early stage BOT, a first peritoneal cytology is recommended (Grade C). For early serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (Grade C). For early stage endometrioid BOT, and in the absence of a desire to maintain fertility, hysterectomy is recommended for initial surgery or if restaging surgery is indicated (Grade C). For endometrioid-type early stage BOT, if there is a desire for fertility preservation, the uterus may be retained subject to good evaluation of the endometrium by imaging and endometrial sampling (Grade C). In case of surgery (initial or restaging if indicated) for early stage BOT, it is recommended to evaluate the macroscopic appearance of the appendix (Grade B). In case of surgery (initial or restaging if indicated) for early stage BOT, appendectomy is recommended only in case of macroscopically pathological appearance of the appendix (Grade C). Pelvic and lumbar aortic lymphadenectomy is not recommended for initial surgery or restaging surgery for early stage BOT regardless of histologic type (Grade C). In case of BOT diagnosed on definitive histology, the indication of restaging surgery should be discussed in Multidisciplinary Collaborative Meeting. For pre umed early stage BOT, it is recommended to use the laparoscopic approach to perform restaging surgery (Grade C). Restaging surgery is recommended for serous BOT with micropapillary appearance and unsatisfactory abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended in case of mucinous BOT if only a cystectomy has been performed or the appendix has not been visualized, then a unilateral adnexectomy will be performed (Grade C). If a restaging surgery is decided in the management of a presumed early stage BOT, the actions to be carried out are as follows: a peritoneal cytology (Grade C), an omentectomy (there is no data in the literature recommending the type of omentectomy to be performed) (Grade B), a complete exploration of the abdominal cavity with peritoneal biopsies on suspect areas or systematically (Grade C), visualization of the appendix +/- the appendectomy in case of pathological macroscopic appearance (Grade C), unilateral adnexectomy in case of mucinous TFO (Grade C).Copyright © 2020 Elsevier Masson SAS

Cano, A., et al. (2024). "Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials." BJOG: An International Journal of Obstetrics and Gynaecology.
	Objective: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. Design(s): Prespecified pooled analysis. Setting(s): USA, Canada, Europe; 2019-2021. Population: 1022 women aged >=40 to <=65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. Method(s): Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). Main Outcome Measure(s): Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. Result(s): Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. Conclusion(s): Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.Copyright © 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.

Canon, C. M., et al. (2021). "SHOULD PATIENTS WITH ONLY TWO EMBRYOS ELIGBILE FOR BIOPSY AFTER A SINGLE CONTROLLED OVARIAN HYPERSTIMULATION CYCLE UTILIZE PGT-A PRIOR TO TRANSFER SELECTION? cycles without PGT-A." Fertility and Sterility 116(3): e246.
	Objective: Preimplantation genetic testing for aneuploidy (PGT‐A) is often utilized to enhance implantation rates by enabling the selection of a euploid embryo for transfer. Clinicians may question whether the use of PGT‐A is beneficial, especially for patients who produce low numbers of embryos after controlled ovarian hyperstimulation (COH).1 Our study aims to assess the potential benefit and/or risk of utilizing PGT‐A prior to embryo transfer in patients with only two available embryos compared to fresh or frozen ET cycles without PGT‐A. Materials and Methods: This study included patients who underwent an IVF cycle and had only two viable embryos available after COH from January 2003 to March 2021. Patients were separated into three groups: Group A: Patients who underwent subsequent single euploid blastocyst FET; Group B: Patients who underwent subsequent single blastocyst FET without the use of PGT‐A; Group C: Patients who underwent fresh double embryo transfer (DET) on day 3 or 5. Patients who utilized PGT‐A were included in the study if they had at least one euploid embryo available for transfer. Basic demographic and cycle characteristics were compared between groups. Statistical analysis was performed using ANOVA, chi‐square, and logistic regression. Results: Of the 949 patients included in this study, 772 underwent a single euploid blastocyst FET, 123 underwent a single FET w/o the use of PGT‐A, and 54 underwent a fresh DET,. All patients attempted at least one embryo transfer cycle, and 102 patients underwent two embryo transfer cycles. Patients who underwent FET with PGT‐A were more likely to become pregnant, and more likely to become pregnant after their first embryo transfer when compared with both FET without PGT‐A patients and Fresh DET (p <0.0001). Negative pregnancy outcomes as defined by a transfer resulting in a biochemical pregnancy, clinical pregnancy loss, or ectopic pregnancy were similar amongst all groups for both the first and second embryo transfer. On multivariate logistic regression, after adjusting for age, BMI, endometrial thickness, and embryo quality, there was a lower odds of pregnancy when undergoing single blastocyst FET without PGT‐A compared to single blastocyst FET with PGT‐A (OR 0.334 95% CI 0.139‐0.805). There was no difference in negative pregnancy outcomes between the groups. Conclusions: A decision must be made for patients with only two embryos available after COH whether to undergo fresh ET (with one or two embryos) or to cryopreserve the embryos with or without the use of PGT‐A. This study uses big data to develop a decision‐support tool to aid physicians in making this decision. Our study demonstrates that in patients who develop only two viable embryos, use of PGT‐A enhances the likelihood of achieving a successful pregnancy compared to patients who underwent a day 3 or 5 fresh DET or single blastocyst FET with untested embryos. Impact Statement: In patients with a low number of embryos per cycle, utilization of PGT‐A leads to higher odds of pregnancy and should be considered over transfer of unscreened embryos. References: 1. Lukassen HGM. Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial. Human reproduction. 2005;20(3):702‐708. doi:10.1093/humrep/deh672

Cao, A., et al. (2023). "Effect of exercise on body composition among women with ovarian cancer." Journal of cancer survivorship : research and practice 17(5): 1386-1396.
	Purpose: Obesity is associated with a higher risk of mortality in women with ovarian cancer. Exercise has improved body composition among cancer survivors, yet no randomized controlled trial has explored the effect of exercise on body composition in women with ovarian cancer. In this analysis, we examined the effect of a six-month aerobic exercise intervention on body composition among ovarian cancer survivors in the Women's Activity and Lifestyle Study in Connecticut (WALC).; Methods: Women with ovarian cancer (N = 144) were randomized in a 1:1 ratio to 6 months of an aerobic exercise intervention or attention-control, and body composition was measured as a secondary outcome at baseline and 6 months via dual-energy X-ray absorptiometry (DEXA). Women with at least one DEXA scan were included in the analysis (N = 103).; Results: On average, participants were 57.1 (± 8.7) years old and 1.6 (± 0.9) years since diagnosis. Women randomized to exercise maintained weight during the trial (- 0.11 kg, P = 0.82), while women in attention-control gained weight (+ 1.40 kg, P = 0.03); however, the between-group difference did not reach statistical significance (P = 0.09). We found no statistically significant differences by study arm for changes in body fat percentage, bone mineral density, or lean body mass.; Conclusions: Weight was maintained as a result of a 6-month aerobic exercise intervention among post-treatment ovarian cancer survivors. Future exercise and healthy eating interventions should consider additional measures (e.g., computer tomography scans, D 3 -creatinine) to more accurately assess changes in body composition.; Implications for Cancer Survivors: Moderate-intensity aerobic exercise may help ovarian cancer survivors maintain weight. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cao, L., et al. (2020). "Comparison of pregnancy outcomes and obstetric complications between frozen embryo transfer and fresh embryo transfer in women with polycystic ovary syndrome a meta-analysis." Journal of Reproductive Medicine 65(9-10): 277-285.
	OBJECTIVE: Frozen embryo transfer (FET) has been confirmed to be an alternative treatment for polycystic ovary syndrome (PCOS) patients. In FET cycles the pregnancy outcomes and obstetric complications are also of great concern. This meta-analysis study was aimed to evaluate pregnancy outcomes and obstetric complications between FET and fresh embryo transfer in women with PCOS. STUDY DESIGN: A literature search in PubMed, Embase, and the Cochrane Library was performed. We included 6 studies evaluating pregnancy outcomes and obstetric complications between FET and fresh embryo transfer in women with PCOS who received in vitro fertilization (IVF) treatment and intracytoplasmic sperm injection (ICSI) in this meta-analysis. The main outcome measures were clinical pregnancy rate, live birth rate, miscarriage rate, preterm birth rate, and mac-rosomia rate. RESULT(S): We included 6 studies, accounting for 3,290 frozen embryo cycles and 3,042 fresh embryo cycles in women with PCOS. Data analysis showed that the rate of miscarriage in the FET group was significantly lower than that of the fresh embryo transfer group. There were no significant differences between the two groups in the rates of clinical pregnancy, live birth, preterm birth, and macrosomia. CONCLUSION(S): Based on the above results, FET should ideally be performed as an appropriate treatment option for PCOS patients because of the lower rate of miscarriage in FET. (J Reprod Med 2020;65:277- 285).Copyright © Journal of Reproductive Medicine, Inc.

Cao, Q., et al. (2019). "Efficacy and safety of moxibustion in patients with chronic prostatitis/chronic pelvic pain syndrome: A systematic review protocol." Medicine 98(20): e15678.
	Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urogenital disease. Moxibustion is a complementary treatment option for CP/CPPS. This systematic review will assess the efficacy and safety of moxibustion as a sole or add-on therapy for CP/CPPS.; Methods: We will retrieve randomized controlled trials (RCTs) of moxibustion for CP/CPPS from the following databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, VIP, Chinese Biomedical Database, China National Knowledge Infrastructure Database, Wanfang Data, Chinese Medicine Database System, Google Scholar, Clinicaltrials.gov, and China Clinical Trial Registry from their inception to March 9, 2019, without language restrictions. RCTs comparing moxibustion with active drugs or moxibustion + drugs with these same drugs alone will be included. Primary outcomes will be the change in the total score of the National Institutes of Health's Chronic Prostatic Inflammatory States Index (NIH-CPSI) after moxibustion treatment. Secondary outcomes will include the scores of the individual NIH-CPSI domains, response to treatment of CP/CPPS, leucocyte and phosphatidylcholine corpuscle count in prostatic fluid, incidence of adverse events (AEs), and incidence of moxibustion-related AEs. The Cochrane risk of bias tool will be used for evaluating the risk of bias of individual trials. Heterogeneity will be detected by the Cochran Q test and I-square test. A random-effects model will be used to pool data in the meta-analysis. Risk ratio and weighted or standardized mean difference will be used as the effect measures. Three sets of subgroup analyses will be performed to explore the sources of heterogeneity. Where appropriate, we will assess the likelihood of publication bias based on funnel plots and quantitative tests.; Results: This study will produce the systematic review evidence regarding moxibustion for treating CP/CPPS based on current RCTs.; Conclusion: This study will provide a clear basis for understanding the efficacy and adverse reactions of moxibustion treatment for CP/CPPS.; Prospero Registration Number: CRD42019121338.

Cao, S.-Y., et al. (2023). "Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis." BMC Cancer 23(1): 31.
	Objective: To compare recurrence and survival in patients with stage III endometrial cancer after radical surgery, followed by either adjuvant chemoradiotherapy (ACR) or adjuvant chemotherapy (AC).; Methods: We searched for relevant studies in PubMed Central, Embase and the Cochrane Central Register of Controlled Trials. Data were pooled on rates of recurrence as well as rates of progression-free, disease-free and overall survival. Heterogeneity was evaluated using the I 2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity.; Results: Data from 18,375 patients in 15 retrospective studies and one randomized controlled trial were meta-analyzed. Compared to the AC group, the ACR showed significantly lower risk of local recurrence (OR 0.43, 95%CI 0.32-0.59) and total recurrence (OR 0.72, 95%CI 0.58-0.89). ACR was also associated with significantly better overall survival (HR 0.66, 95%CI 0.57-0.76), progression-free survival (HR 0.56, 95%CI 0.39-0.81) and disease-free survival (HR 0.66, 95%CI 0.53-0.83).; Conclusions: Adding adjuvant radiotherapy to adjuvant chemotherapy after radical surgery may significantly reduce risk of local and overall recurrence, while significantly improving survival of patients with stage III endometrial cancer. (© 2023. The Author(s).)

Cao, Y., et al. (2023). "Retroperitoneal drainage after radical gynecological malignancies: a systematic review and meta-analysis."
	
Cao, Y., et al. (2021). "Efficacy and safety of acupuncture for postpartum depression: A systematic review." Chinese Journal of Evidence-Based Medicine 21(8): 922-928.
	Objective To systematically review the efficacy and safety of acupuncture on postpartum depression (PPD). Methods PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of acupuncture in treatment of PPD from inception to February 2021. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed by using Stata16.0 software. Results A total of 13 RCTs involving 899 patients were included. The results of meta-analysis showed that there was no significant difference between hand acupuncture and fluoxetine hydrochloride in HAMD score (MD=0.45, 95%CI -0.52 to 1.41, P=0.36), clinical effective rate (RR=0.93, 95%CI 0.70 to 1.23, P=0.59), and clinical cure rate (RR=0.88, 95%CI 0.44 to 1.76, P=0.73). However, hand acupuncture was superior in safety to fluoxetine hydrochloride (RR=0.04, 95%CI 0.01 to 0.28, P<0.05). There was no significant difference in clinical effective rate (RR=1.08, 95%CI 0.87 to 1.36, P=0.49) and cure rate (RR=1.31, 95%CI 0.84 to 2.04, P=0.24) between both groups. Conclusions The current evidence shows that there are no differences between hand acupuncture and non-acupuncture in reducing HAMD score, improving the clinical effective rate and clinical cure rate. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.Copyright © 2021 West China University of Medical Science. All rights reserved.

Cao, Y. R., et al. (2020). "Effects of endometrial stimulation timings and techniques on pregnancy outcomes in patients without prior embryo transfer: A systematic review and meta-analysis." Reproductive and Developmental Medicine 4(3): 191-193.
	Objective: To investigate the effects of endometrial stimulation timings and techniques on pregnancy outcomes in patients without prior embryo transfer (ET). Method(s): We included a total of 10 studies related to the impact of endometrial stimulation on the pregnancy outcome of infertile patients with the first ET from 2010 to 2019. These studies were found by searching databases including China Science and Technology Journal Database (VIP), Chinese Biological Med (CBM), Chinese Medical Current Content (CMCC), China National Knowledge Internet (CNKI), WanFang Med Online, Cochrane Library, Web of Science, PubMed, Medline, ScienceDirect, and EMBASE. A total of 1,983 cycles were included, of which 725 were cycles with endometrial stimulation. Clinical outcomes included clinical pregnancy, implantation, abortion, multiple pregnancy, and live birth rate. Result(s): The implantation rate (IR) was higher in the fresh cycle endometrial stimulation group than in the control group (relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.03-1.42; P = 0.02), but there were no significant between-group differences in the live birth rate (LBR) and abortion rate (AR). Subgroup analysis showed that whether follicular or luteal endometrial stimulation was performed before the ET cycle had no effect on the clinical pregnancy outcome, and endometrial stimulation on the day of oocyte retrieval reduced the clinical pregnancy rate (CPR) (RR = 0.37, 95% CI = 0.19-0.75; P = 0.005). Whether the technique involved the use of a curette or catheter, there was no significant between-group difference in CPR. Conclusion(s): Fresh cycle endometrial stimulation can improve the embryo IR in patients without prior ET, but it cannot increase CPR, LBR, or AR. Subgroup analysis showed that different endometrial stimulation timings and techniques did not significantly improve CPR and that endometrial stimulation on the day of oocyte retrieval reduced CPR.Copyright © 2020 Reproductive and Developmental Medicine Published by Wolters Kluwer - Medknow.

Capalbo, G., et al. (2023). "Laparoscopic Versus Abdominal Radical Hysterectomy." American Journal of Clinical Oncology: Cancer Clinical Trials 46(2): 85.
	
Capezzuoli, T., et al. (2022). "Gynaecologic and Systemic Comorbidities in Patients with Endometriosis: Impact on Quality of Life and Global Health." Clinical and Experimental Obstetrics and Gynecology 49(7): 157.
	Objectives: Endometriosis is an inflammatory disease characterized by a frequent association with gynecologic and systemic comorbidities. Our aim was to evaluate which gynecologic and systemic comorbidities occur in women affected by endometriosis and their impact on quality of life and global health. Mechanism: A literature search of the PubMed, Cochrane Library, Scopus and Web of Science databases was performed to identify the relevant studies published before December 31, 2021. We selected clinical studies, systematic reviews, and meta-analyses in English. Findings in Brief: Endometriosis is strongly associated with gynecologic (adenomyosis, uterine fibroids, polycystic ovarian syndrome-PCOS) and systemic (autoimmune, inflammatory, psychiatric and neurological disorders) comorbidities that impair women quality of life and global health through multiple mechanisms, influencing everyday life and work activities. Conclusion(s): Endometriosis is a chronic disease, impairing multiple functioning areas and affecting women's health and everyday life. Considering the co-existence of multiple both gynecological and non-gynecological disorders, endometrisois needs a multidisciplinary approach. Thus, specialized referral centres are warranted for a personalized management, focused on patient symptoms and comorbidities.Copyright © 2022 The Author(s).

Capobianco, G., et al. (2020). "Efficacy and effectiveness of bulking agents in the treatment of stress and mixed urinary incontinence: A systematic review and meta-analysis." Maturitas 133: 13-31.
	The objective of this systematic review and meta-analysis was to evaluate the efficacy and the effectiveness, as well as the safety and tolerability, of urethral bulking agents (UBAs) in women with mixed or stress urinary incontinence. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were used to identify relevant articles. In total, 3510 records were found. A total of 42 full texts were evaluated but only 21 (48.8 %) were selected for the qualitative and quantitative analysis. The pooled improvement rate in studies with a follow-up of <=1 and >1 year was 46.0 % (95 % CI: 37.0 %-57.0 %; I2: 88.9 %) and 57.0 % (95 % CI: 39.0 %-74.0 %; I2: 89.6 %), respectively. The outcome 'cure/dryness' ranged from 9.1 % to 56.7 %. The pooled cure rate was 26.0 % (95 % CI: 21.0 %-32.0 %; I2: 89.9 %) and 21.0 % (95 % CI: 16.0 %-27.0 %; I2: 34.2 %) in females with a follow-up of <=1 and >1 year, respectively. The treatment success rate ranged from 32.7 % to 93.3 % in 12 studies; it was objectively assessed with different tools (e.g., the Stamey scale in 5 studies). The pooled objective treatment success rate was 7.0 % (95 % CI: 59.0.0 %-75.0 %; I2: 82.4 %) and 46.0 % (95 % CI: 37.0 %-55.0 %; I2: 55.3 %) in women with a follow-up of <=12 and >12 months, respectively. The percentage of adverse events was 0.4 % (vaginal infection, irritation, lichen sclerosus, worsening urinary incontinence). However, the use of UBAs as the first-line therapy should be demonstrated in more comparative studies (randomized studies MUSs vs. UBAs). UBAs should be considered a first-line surgical therapy only for women with SUI and mixed UI with high anaesthesia risk, elderly patients, or patients reluctant to undergo surgery. Thus, UBAs should not be offered as first-line therapy for those women desiring a "one-time" durable solution for primary or recurrent SUI.Copyright © 2019 Elsevier B.V.

Capodaglio, P., et al. (2024). "Rehabilitation combined with dietary intervention improve urinary incontinence in women with obesity: A proof-of-principle study." Turkish Journal of Physical Medicine and Rehabilitation 70(1): 39-46.
	Objectives: This study aimed to assess the impact of add-on pelvic floor exercises on a weight management rehabilitation program. Patients and Methods: This proof of principle study was conducted between July 2019 and December 2019. Ninety-three adult female inpatients with obesity and diagnosis of urinary incontinence (UI) were assessed for inclusion, and the suitable patients were randomly assigned to the experimental group and the control group. Both groups underwent a weight management rehabilitation program, while the experimental group also performed pelvic floor exercises. The primary outcome was UI severity, assessed by the 1-h pad test. Secondary outcomes were urinary symptoms, assessed by the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Patient Global Impression of Improvement (PGI-I), and Incontinence Quality of Life Questionnaire (I-QOL). Result(s): Sixty female inpatients were randomly assigned to the experimental group [n=30; median age: 64.50 (51.25 to 70.50) years] or the control group [n=30; median age: 67.50 (58.50 to 74.75) years]. The experimental group showed a statistically significant reduction in UI severity [pad test: 2.08 (1.21 to 8.85) g vs. 0.54 (0.24 to 1.13) g, p<0.01; ICIQ-SF: 14.00 (10.25 to 17.00) vs. 8.00 (6.25 to 11.75), p<0.01; I-QOL: 56.37 (42.28 to 73.64) vs. 78.64 (64.32 to 90.68), p<0.01]. Statistically significant differences were found in the between-groups analysis [pad test: 0.54 (0.24 to 1.13) g vs. 1.08 (0.83 to 3.86) g, p<0.01; ICIQ-SF: 8.00 (6.25 to 11.75) vs. 12.00 (10.00 to 16.00), p<0.01; I-QOL: 78.64 (64.32 to 90.68) vs. 68.18 (60.00 to 84.32), p<0.01]. Conclusion(s): Including pelvic floor exercises might provide additional benefits compared to standard rehabilitation in reducing UI symptoms in obese women.Copyright © 2024 Turkish Society of Physical Medicine and Rehabilitation. All rights reserved.

Capogrosso, P., et al. (2019). "Low-Intensity Shock Wave Therapy in Sexual Medicine-Clinical Recommendations from the European Society of Sexual Medicine (ESSM)." The Journal of Sexual Medicine 16(10): 1490-1505.
	Introduction: Low-intensity shockwave therapy (LISWT) has been investigated for the treatment of uroandrological disorders including erectile dysfunction (ED), Peyronie's disease (PD) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with controversial findings.; Aim: To review the evidence on LISWT for ED, PD, and CP/CPPS and provide clinical recommendations on behalf of the European Society of Sexual Medicine.; Methods: Medline and Embase databases were searched for randomized clinical trials (RCTs), meta-analyses and open-label prospective or retrospective studies investigating the effect of LISWT on ED, PD, or CP/CPPS.; Outcomes: The panel provided statements on clinically relevant questions concerning LISWT: (i) treatment efficacy, (ii) treatment protocol, (iii) clinical indications, and (iv) safety. The level of evidence was provided according to the Oxford 2011 criteria and graded using the Oxford Centre for Evidence-Based Medicine recommendations.; Results: 11 RCTs and 5 meta-analyses investigated LISWT for ED. RCTs provided controversial results on the efficacy of LISWT and were affected by high heterogeneity and the small number of patients included. Pooled-data analysis showed an overall positive effect in terms of erectile function improvement but reported small estimates and included a largely heterogeneous cohort of patients. 4 RCTs and 1 meta-analysis assessed LISWT for PD. All trials showed positive findings in terms of pain relief but no effect on penile curvature and plaque size. Inclusion criteria vary widely among studies, and further investigation is needed. 5 RCTs investigated LISWT for CP/CPPS. Data showed a possible effect on pain relief, although there is no evidence supporting that pain relief was maintained or any improvement in pain over time.; Clinical Implications: LISWT needs to be further investigated in the context of sexual medicine and is almost but not yet ready for clinical practice.; Strengths and Limitations: All studies have been evaluated by a panel of experts providing recommendations for clinical practice.; Conclusions: LISWT is a safe and well-tolerated procedure but its efficacy for the treatment of ED is doubtful and deserves more investigation. Patients reporting pain associated with PD may benefit from LISWT, although no effect is expected on disease progression. LISWT is not a primary treatment for CP/CPPS, but it may be considered as an option to relieve pain. Capogrosso P, Frey A, Jensen CFS, et al. Low-Intensity Shock Wave Therapy in Sexual Medicine-Clinical Recommendations from the European Society of Sexual Medicine (ESSM). J Sex Med 2019;16:1490-1505. (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Capote, S., et al. (2022). "Small Cell Carcinoma of the Vagina: First Systematic Review of Case Reports and Proposal of a Management Algorithm." Journal of Lower Genital Tract Disease.
	OBJECTIVES: Small cell carcinoma of the vagina (SmCCV) is an extremely rare disease. Evidence-based data and specific guidelines are lacking. We conducted the first systematic review of case reports to provide the most overall picture of SmCCV. MATERIALS AND METHODS: Literature search in PubMed and Scopus was performed using the terms "small cell carcinoma" and "vagina." English-language case reports of primary SmCCV up to January 2022 were included. RESULTS: Twenty-nine articles describing 44 cases met our inclusion criteria. We report a new case of our hospital. The global median overall survival (mOS) was 12.00 months (95% CI = 9.31-14.69). The mOS was not reached for stage I, and it was 12.00, 12.00, 9.00, and 8.00 months for stages II, III, IVA, and IVB, respectively (statistically significant differences between stage I and stages II, III, or IVA [log rank p = .003-.017]). Thirty-five cases received local treatments (77.8%). The mOS of patients treated with surgery ± complementary chemotherapy, radiotherapy ± complementary chemotherapy, chemoradiation ± complementary chemotherapy, and surgery + radiotherapy ± complementary chemotherapy were 11.00, 12.00, 17.00, and 29.00 months, respectively. The use of adjuvant or neoadjuvant chemotherapy (64.5%, mostly platinum + etoposide) showed longer mOS (77.00 vs 15.00 months). Four of 5 tested cases presented human papillomavirus infection, 3 of them presenting type 18. CONCLUSIONS: Small cell carcinoma of the vagina shows dismal prognosis. Multimodal local management plus complementary chemotherapy seems to achieve better outcomes. Human papillomavirus could be related to the development of SmCCV. A diagnostic-therapeutic algorithm is proposed.

Capozzi, V. A., et al. (2021). "The robotic single-port platform for gynecologic surgery: a systematic review of the literature and meta-analysis." Updates in surgery 73(3): 1155-1167.
	Since the first robotic single-site hysterectomy was performed, the research focused on the use of robotic single-site surgery (RSSS) for all gynecological conditions. This review aims to examine the studies available in the literature on RSSS in gynecology both for benign and malignant indications. The systematic review was carried out in agreement with the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). All the articles were grouped into three sets based on the surgical indication (Group 1, 2, and 3 for benign, malignant, and mixed diseases, respectively). Two hundred and fifty total studies were analyzed, and 27 articles were included in the review. A total of 1065 patients were included in the analysis. Of these, 605 patients were included in group 1, 260 in group 2, and 200 in group 3. Ten (1.7%) patients with benign pathology, 16 (6.2%) patients with malignant disease, and 5 (2.5%) patients with both diseases developed major complications. Two (0.3%) patients in group 1, 3 (1.2%) patients in group 2 and 5 (2.5%) in group 3 were converted to a different type of surgery. No significant differences were found between groups for BMI (p=0.235), operative time (p=0.723), estimated blood loss (EBL) (p=0.342), and hospital stay (p=0.146). The complications and conversions incidence through pooled analysis showed a higher general conversion rate (p=0.012) in group 3 (3.0%) and higher complications rate (p=0.001) in group 2 (5.3%) compared to the other groups. RSSS seems to be a feasible and safe procedure for all gynecological surgical procedures. A long-term analysis would be necessary before considering the RSSS oncologically safe for patients with malignant disease.

Capozzi, V. A., et al. (2020). "Endometrial stromal sarcoma: A review of rare mesenchymal uterine neoplasm." The Journal of Obstetrics and Gynaecology Research 46(11): 2221-2236.
	Objective: This review aims to analyze the pathological aspects, diagnosis and treatment of rare mesenchymal uterine tumors.; Methods: On August 2019, a systematic review of the literature was done on Pubmed, MEDLINE, Scopus, and Google Scholar search engines. The systematic review was carried out in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes statement (PRISMA). The following words and key phrases have been searched: "endometrial stromal sarcoma", "low-grade endometrial stromal sarcoma", "high-grade endometrial stromal sarcoma", "uterine sarcoma", "mesenchymal uterine tumors" and "uterine stromal sarcoma". Across these platforms and research studies, five main aspects were analyzed: the biological characteristics of the neoplasms, the number of cases, the different therapeutic approaches used, the follow-up and the oncological outcomes.; Results: Of the 94 studies initially identified, 55 were chosen selecting articles focusing on endometrial stromal sarcoma. Of these fifty-five studies, 46 were retrospective in design, 7 were reviews and 2 randomized phases III trials.; Conclusion: Endometrial stromal sarcomas are rare mesenchymal uterine neoplasms and surgery represents the standard treatment. For uterus-limited disease, the remove en bloc with an intact resection of the tumor (without the use of morcellation) is strongly recommended. For advanced-stage disease, the standard surgical treatment is adequate cytoreduction with metastatectomy. Pelvic and para-aortic lymphadenectomy is not recommended in patients with Low-grade Endometrial Stromal Sarcoma (ESS), while is not clear whether cytoreduction of advanced tumors improves patient survival in High-grade ESS. Administration of adjuvant radiotherapy or chemotherapy is not routinely used and its role is still debated. (© 2020 Japan Society of Obstetrics and Gynecology.)

Capozzi Vito, A., et al. (2021). "Obstetrics outcomes after complete and partial molar pregnancy: Review of the literature and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 259: 18-25.
	The hydatidiform mole is a rare gynecological disease rising from the trophoblastic. Post-molar pregnancies have an extremely variable course, varying from repeated abortions, stillbirths, preterm births, live births, or recurring in further molar pregnancies. Literature on obstetric outcomes following molar pregnancy is poor, often including monocentric studies, and with data collected from national databases. This review and meta-analysis aim to analyze the obstetric outcomes after conservative management of complete (CHM) and partial (PHM) molar pregnancies. The meta-analysis was performed following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). Six studies met the inclusion. Of the total 25,222 patients, 13,129 complete (52.1 %) and 12,093 partial (47.9 %) molar pregnancies were included. Live births rate after CHM was statistically higher (p = 0.002) compared to the live births after PHM (53.6 % vs. 51.0 %, 3266 vs. 1807 cases, respectively). Studies showed heterogeneity I 2 = 57.7 %, pooled proportion = 0.2 %, and 95 % Confidence Interval (CI) 0.6 to 0.9. No statistically significant difference was demonstrated for ectopic pregnancies (p = 0.633), miscarriage (p = 0.637), preterm birth (p = 0.865), stillbirth (p = 0.911), termination of pregnancy (p = 0.572), and complete molar recurrence (p = 0.580) after CHM and PHM. Partial molar recurrence occurred more frequently after PHM than CHM (0.4 % vs. 0.3 %, 52 vs. 37 cases, respectively, p = 0.002). Careful counseling on the obstetric subsequent pregnancies outcomes should be provided to patients eager for further pregnancy and further studies are needed to confirm these results.; Competing Interests: Declaration of Competing Interest The authors report no declarations of interest. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Capozzi Vito, A., et al. (2021). "Peripherally Inserted Central Venous Catheters (PICC) versus totally implantable venous access device (PORT) for chemotherapy administration: a meta-analysis on gynecological cancer patients." Acta bio-medica : Atenei Parmensis 92(5): e2021257.
	Background and Aim: Ninety-four thousand gynecological cancer diagnoses are performed each year in the United States. The majority of these tumors require systemic adjuvant therapy. Sustained venous access was overcome by indwelling long-term central venous catheter (CVC). The best choice of which CVC to use is often arbitrary or dependent on physician confidence. This meta-analysis aims to compare PORT and peripherally inserted central catheter (PICC) outcomes during adjuvant treatment for gynecological cancer.; Methods: Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA)were used to conduct the meta-analysis.; Results: 1320 patients were included, 794 belonging to the PORT group and 526 to the PICC group. Total complication rates were fewer in the PORT group, p = 0.05. CVC malfunction was less frequent in the PORT group than in the PICC group, p <0.01. Finally, thrombotic events were less expressed in the PORT group than in the PICC group, p = 0.02. No difference was found in operative complication, migration, malposition, extravasation, infection, and complication requiring catheter removal.; Conclusions: PORT had fewer thrombotic complications and fewer malfunction problems than PICC devices. Unless specific contraindications, PORTs can be preferred for systemic treatment in gynecological cancer patients.

Capozzi Vito, A., et al. (2022). "Update of Robotic Surgery in Benign Gynecological Pathology: Systematic Review." Medicina (Kaunas, Lithuania) 58(4).
	Background and Objectives : Since the Food and Drug Administration's (FDA) approval in 2005, the application of robotic surgery (RS) in gynecology has been adopted all over the world. This study aimed to provide an update on RS in benign gynecological pathology by reporting the scientific recommendations and high-value scientific literature available to date. Materials and Methods: A systematic review of the literature was performed. Prospective randomized clinical trials (RCT) and large retrospective trials were included in the present review. Results: Twenty-two studies were considered eligible for the review: eight studies regarding robotic myomectomy, five studies on robotic hysterectomy, five studies about RS in endometriosis treatment, and four studies on robotic pelvic organ prolapse (POP) treatment. Overall, 12 RCT and 10 retrospective studies were included in the analysis. In total 269,728 patients were enrolled, 1721 in the myomectomy group, 265,100 in the hysterectomy group, 1527 in the endometriosis surgical treatment group, and 1380 patients received treatment for POP. Conclusions: Currently, a minimally invasive approach is suggested in benign gynecological pathologies. According to the available evidence, RS has comparable clinical outcomes compared to laparoscopy (LPS). RS allowed a growing number of patients to gain access to MIS and benefit from a minimally invasive treatment, due to a flattened learning curve and enhanced dexterity and visualization.

Capozzi Vito, A., et al. (2023). "Optimal Management for Stage IVB Endometrial Cancer: A Systematic Review." Cancers 15(21).
	(1) Background: Endometrial cancer (EC) is a common gynecological malignancy, often diagnosed at an early stage with a high overall survival rate. Surgical treatment is the primary approach, guided by pathological and molecular characteristics. Stage IVB EC, characterized by intra and/or extra-abdominal metastasis, presents a significant challenge with no clear consensus on optimal management. (2) Methods: A systematic literature review was conducted from January to May 2023, covering studies from 2000 to 2023. Eligible studies included retrospective case series, prospective trials, and randomized clinical trials. (3) Results: Of 116 studies identified, 21 were deemed relevant: 7 on primary surgery, 10 on neoadjuvant chemotherapy (NACT), and 4 on adjuvant treatment. Notably, the impact of residual tumor after primary surgery was a critical factor affecting survival. The use of NACT followed by interval debulking surgery showed promise, particularly in cases deemed unresectable. Adjuvant treatment, combining radiotherapy and chemotherapy, demonstrated improved survival but lacked consensus regarding its role. (4) Conclusions: Stage IVB EC poses a complex challenge with limited evidence to guide management. Optimal cytoreduction remains crucial, and NACT should be considered for unresectable cases. Multimodality adjuvant therapy may benefit patients, even with disease spread beyond the pelvis. Future advances in molecular classification and targeted therapies are expected to enhance treatment strategies.

Capozzi Vito, A., et al. (2021). "Transperitoneal versus extraperitoneal laparoscopic aortic lymph nodal staging for locally advanced cervical cancer: A systematic review and meta-analysis." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47(9): 2256-2264.
	Cervical cancer is the fourth most common neoplasm in women. In locally advanced cervical cancers, the international guidelines recommend nodal aortic assessment. Two techniques have been described to perform laparoscopic aortic lymphadenectomy: transperitoneal laparoscopic lymphadenectomy (TLL) and extraperitoneal laparoscopic lymphadenectomy (ELL). This meta-analysis aims to compare the surgical outcomes of TLL and ELL for staging purposes. The systematic review was carried out in agreement with the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA). Two hundred and twenty studies were analyzed, and 19 studies were included in the review (7 for TLL and 12 for ELL group). 1112 patients were included in the analysis: 390 patients were included in group 1 and 722 patients in group 2.38 patients (9.7%) in the TLL group and 69 (9.5%) patients in the ELL group developed major complications. The analysis of all complications (intraoperative and postoperative) rate through pooled analysis did not show a significant difference between the two groups (p = 0.979), although a significantly higher intraoperative complication rate (p = 0.018) occurred in the TLL group compared to ELL. No significant differences were found between groups for BMI (p = 0.659), estimated blood loss (p = 0.889), length of stay (p = 0.932), intraoperative time (p = 0.932), conversion to laparotomy rate (p = 0.404), number of lymph node excised (p = 0.461) and postoperative complication (p = 0.291). TLL approach shows a higher rate of intraoperative complications, while no significant difference was found between the two techniques when postoperative complications were analyzed.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Carbajo-García María, C., et al. (2022). "Histone deacetylase inhibition by suberoylanilide hydroxamic acid: a therapeutic approach to treat human uterine leiomyoma." Fertility and Sterility 117(2): 433-443.
	Objective: To evaluate the effect of inhibition of histone deacetylases (HDACs) by suberoylanilide hydroxamic acid (SAHA) treatment of human uterine leiomyoma primary (HULP) cells in vitro on cell proliferation, cell cycle, extracellular matrix (ECM) formation, and transforming growth factor β3 (TGF-β3) signaling.; Design: Prospective study comparing uterine leiomyoma (UL) vs. adjacent myometrium (MM) tissue and cells with or without SAHA treatment.; Setting: Hospital and university laboratories.; Patient(s): Women with UL without any hormone treatment.; Intervention(s): Myomectomy or hysterectomy surgery in women for leiomyoma disease.; Main Outcome Measure(s): HDAC activity was assessed by enzyme-linked immunosorbent assay, and gene expression was assessed by quantitative real-time polymerase chain reaction. Effects of SAHA on HULP cells were analyzed by CellTiter (Promega, Madison, Wisconsin), Western blot, and quantitative real-time polymerase chain reaction.; Result(s): The expression of HDAC genes (HDAC1, fold change [FC] = 1.65; HDAC3, FC = 2.08; HDAC6, FC = 2.42) and activity (0.56 vs. 0.10 optical density [OD]/h/mg) was significantly increased in UL vs. MM tissue. SAHA decreased HDAC activity in HULP cells but not in MM cells. Cell viability significantly decreased in HULP cells (81.68% at 5 μM SAHA, 73.46% at 10 μM SAHA), but not in MM cells. Proliferating cell nuclear antigen expression was significantly inhibited in SAHA-treated HULP cells (5 μM SAHA, FC = 0.556; 10 μM SAHA, FC = 0.622). Cell cycle markers, including C-MYC (5 μM SAHA, FC = 0.828) and CCND1 (5 μM SAHA, FC = 0.583; 10 μM SAHA, FC = 0.482), were significantly down-regulated after SAHA treatment. SAHA significantly inhibited ECM protein expression, including FIBRONECTIN (5 μM SAHA, FC = 0.815; 10 μM SAHA, FC = 0.673) and COLLAGEN I (5 μM SAHA, FC = 0.599; 10 μM SAHA, FC = 0.635), in HULP cells. TGFβ3 and MMP9 gene expression was also significantly down-regulated by 10 μM SAHA (TGFβ3, FC = 0.596; MMP9, FC = 0.677).; Conclusion(s): SAHA treatment inhibits cell proliferation, cell cycle, ECM formation, and TGF-β3 signaling in HULP cells, suggesting that histone deacetylation may be useful for treatment of UL. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Carcelén-Fraile María Del, C., et al. (2022). "Changes in satisfaction with female genital self-image and sexual function after a Qigong exercise intervention in Spanish postmenopausal women: a randomized-controlled trial." Menopause (New York, N.Y.) 29(6): 693-699.
	Objective: To analyze the effectiveness of a Qigong exercise program on satisfaction with female genital self-image and female sexual function in postmenopausal Spanish women.; Methods: A total of 49 women were randomly assigned to an experimental group (n = 22) that carried out training based on Qigong exercises for 12 weeks and a control group (n = 27) that did not carry out any type of intervention. Female genital self-image was measured through the Female Genital Self-Tmage Scale and female sexual function through the Female Sexual Function Tndex; both variables were measured before and just after the intervention.; Results: Results showed that women who participated in the Qigong exercise program showed significant improvements with respect to female genital self-image, as well as in the domains of desire, arousal, lubrication, satisfaction, and pain and the total score of the Female Sexual Function Index, but, on the contrary, were not found in the orgasm domain.; Conclusions: Our results suggest that Qigong has the potential to improve female genital self-image and female sexual function among postmenopausal Spanish women.; Competing Interests: Financial disclosure/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Carcelén-Fraile María Del, C., et al. (2022). "Qigong for mental health and sleep quality in postmenopausal women: A randomized controlled trial." Medicine 101(39): e30897.
	Background: Menopause is one of the stages in a woman's life that affects her psychological health, the most frequent being anxiety and depression. In addition, another problem related to this stage is the lack of sleep that causes a decrease in the quality of sleep. The purpose of this randomized controlled trial was to analyze the effectiveness of a Qigong exercise program on sleep quality, anxiety, and depression in Spanish postmenopausal women.; Methods: A total of 125 women were randomly assigned to an experimental group (EG) (n = 63) that carried out a Qigong exercise program for 12 weeks, or a control group (CG) (n = 62), which did not perform any type of intervention. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).; Results: Women who underwent an intervention program experienced significant improvements for all measured variables, except for the use of sleeping medication and daytime dysfunctions that did not show any significant effect with respect to the group and group × time interaction.; Conclusions: After an intervention based on a BaDuanJin Qigong exercise program for 12 weeks, improvements were observed in sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, the total score of the PSQI, anxiety and depression in postmenopausal Spanish women.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cardenas-Goicoechea, J., et al. (2019). "Minimally invasive interval cytoreductive surgery in ovarian cancer: systematic review and meta-analysis." Journal of Robotic Surgery 13(1): 23-33.
	The introduction of minimally invasive surgery in other gynecologic cancers has shown benefits with similar oncologic outcomes. However, the biology and complexity of surgery for ovarian cancer may preclude this approach for ovarian cancer patients. Our objective is to assess feasibility to achieve complete cytoreductive surgery after neoadjuvant chemotherapy for stage IIIC-IV ovarian cancer patients via minimally invasive surgery. Our data sources include PubMed, Embase, Scopus, Biosis, Clinicaltrials.gov, and the Cochrane Library. Meta-analysis was performed using the random-effects model with DerSimonian and Laird estimator for the amount of heterogeneity to estimate the pooled outcomes. A funnel plot and Egger's regression test were used to test publication bias. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. There were 6 studies (3 prospective, 3 retrospective) that met the criteria for meta-analysis with a total of 3231 patients, 567 were in the minimally invasive group and 2664 in the laparotomy group. Both groups were similar in stage and serous histology. Complete cytoreductive surgery was achieved in 74.50% (95% CI 40.41-97.65%) and 53.10% (95% CI 4.88-97.75%) of patients in the minimally invasive and laparotomy groups, respectively. There was no statistical significant difference between these 2 pooled proportions (p = 0.52). Three studies compared minimally invasive surgery vs laparotomy. No significant difference was observed between the 2 groups in obtaining complete cytoreductive surgery [OR = 0.90 (95% CI 0.70-1.16; p = 0.43)]. A symmetrical funnel plot indicated no publication bias. The pooled proportion for grade > 2 postoperative complications was not significant among the laparoscopy group [3.11% (95% CI 0.00-10.24%; p = 0.15)]. Complete cytoreductive surgery appears feasible and safe with minimally invasive surgery in selected advanced ovarian cancer patients after neoadjuvant chemotherapy.

Cardenas-Trowers, O., et al. (2021). "Effect of bladder instillations with versus without triamcinolone acetonide on symptoms of interstitial cystitis/bladder pain syndrome in women: a randomized controlled trial." Neurourology and Urodynamics 40(SUPPL 1): S39‐S40.
	Introduction: Data on the efficacy of bladder instillation (BI) and use of steroids in BI for the treatment of interstitial cystitis/bladder pain syndrome (IC/ BPS) are limited. This study evaluated the utility of adding the steroid, triamcinolone acetonide, in BI for treatment of IC/BPS in women. Methods: Thiswas a single‐center, randomized, doubleblind, comparator‐controlled trial conducted from January 2019 to October 2020 that compared symptom response in women with IC/BPS who underwent 6 weekly BIs (containing heparin (10,000 units), 2% viscous lidocaine (10 mL), 8.4% sodium bicarbonate (15 mL of 1 mEq/mL), and 0.5% bupivacaine (10 mL of 5 mg/mL)) with or without intravesical triamcinolone acetonide (1 vial, 40 mg/1 mL). The primary outcome was the change in IC/BPS symptoms from baseline to the 6th BI based on the total score on the O'Leary Sant Questionnaire; range, 0 to 36 points with higher scores indicating worse symptoms; minimal clinically important difference, 4 points. Secondary outcomes included changes in the scores on the Pelvic Pain and Urgency/Frequency Questionnaire, Overactive Bladder Questionnaire, Pelvic Floor Distress Inventory, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (used to assess rates of sexual activity and dyspareunia), and visual analog pain scale from baseline to the 3rd and 6th BIs. A higher score on each of these instruments indicates worse symptoms. Results: Ninety women (n=45, BI without triamcinolone acetonide; n=45, BI with triamcinolone acetonide) were randomized (mean [SD] age, 42.0 years [14.4]) with 71 (79%) women providing data for the intention‐to‐treat analyses. Women in both treatment groups had improvement in their IC/BPS symptoms as indicated by a decrease in the total score on the O'Leary Sant Questionnaire from baseline to the 6th BI. This positive treatment response was not significantly different between the two groups. There was an improvement in all of the secondary outcomes, except for rates of sexual activity and dyspareunia, for both treatment groups from baseline to the 6th BI, but no significant between‐group differences. The adverse event rates for both groups were low. Conclusion: BI is a safe, effective treatment for women with IC/BPS. The addition of triamcinolone acetonide to a standard BI does not further improve treatment response.

Cardenas-Trowers, O. O., et al. (2021). "Bladder Instillations With Triamcinolone Acetonide for Interstitial Cystitis-Bladder Pain Syndrome: a Randomized Controlled Trial." Obstetrics and Gynecology 137(5): 810‐819.
	OBJECTIVE: To evaluate the utility of adding triamcinolone acetonide to a standard bladder instillation solution for treatment of interstitial cystitis‐bladder pain syndrome. METHODS: This was a single‐center, randomized, double‐blind trial that compared symptom response in women with interstitial cystitis‐bladder pain syndrome who underwent six bladder instillations with triamcinolone acetonide or six instillations without. All instillation solutions contained heparin, viscous lidocaine, sodium bicarbonate, and bupivacaine. The primary outcome was the change in interstitial cystitis‐bladder pain syndrome symptoms from the first to sixth bladder instillation between groups based on the total OLS (O'Leary‐Sant Questionnaire) score. Assuming a 4.03‐point or larger difference in the mean total OLS score from the first to sixth bladder instillation as compared between the groups, 64 participants were needed to show a significant difference with 80% power at the 0.05 significance level. RESULTS: From January 2019 to October 2020, 90 women were enrolled‐45 per group; 71 (79%) completed all six bladder instillations. Randomization resulted in groups with similar characteristics. There was no difference between groups in the primary outcome (bladder instillation with triamcinolone acetonide: mean OLS change ‐6.7 points, 95% CI 4.6‐8.8 and bladder instillation without triamcinolone acetonide: mean OLS change ‐5.8 points, 95% CI 3.4‐8.1; P=.31). Women in both groups had improvement in their interstitial cystitis‐bladder pain syndrome symptoms as indicated by a decrease in the total OLS score from the first to sixth bladder instillation. CONCLUSION: The addition of triamcinolone acetonide to a standard bladder instillation solution does not improve symptoms associated with interstitial cystitis‐bladder pain syndrome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03463915.

Cardim Hilton Jose, P., et al. (2023). "EFFICACY AND SAFETY OF OVARIAN STEM CELL TRANSPLANTATION IN PATIENTS WITH PRIMARY OVARIAN INSUFFICIENCY AND POOR OVARIAN RESPONSE: A SYSTEMATIC REVIEW." International Journal of Health Science 3(15).
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Cardoso, B. R., et al. (2024). "Nut Consumption and Fertility: a Systematic Review and Meta-Analysis." Advances in nutrition (Bethesda, Md.) 15(1): 100153.
	The high concentration of omega-3 polyunsaturated fats, dietary fibers, vitamins, minerals, and polyphenols found in nuts suggest their regular consumption may be a simple strategy for improving reproductive health. This systematic review and meta-analysis aimed to present up-to-date evidence regarding the association between nut intake and fertility outcomes in males and females. Ovid MEDLINE, Embase, CINAHL, and Scopus were searched from inception to 30 June 2023. Eligible articles were interventional or observational studies in human subjects of reproductive age (18-49 y) that assessed the effects (or association) of dietary nut consumption (for a minimum of 3 mo) on fertility-related outcomes. Random-effects meta-analyses were completed to produce a pooled effect estimate of nut consumption on sperm total motility, vitality, morphology, and concentration in healthy males. Four studies involving 875 participants (646 males, 229 females) were included in this review. Meta-analysis of 2 RCTs involving 223 healthy males indicated consumption of >= 60g nuts/d increased sperm motility, vitality, and morphology in comparison to controls but had no effect on sperm concentration. Nonrandomized studies reported no association between dietary nut intake and conventional sperm parameters in males, embryo implantation, clinical pregnancy or live birth in males and females undergoing ART. Our meta-analysis shows that including at least 2 servings of nuts daily as part of a Western-style diet in healthy males improves sperm parameters, which are predictors of male fertility. Due to their nutritional profile, nuts were found to have potential to promote successful reproductive outcomes. This trial was registered at PROSPERO (CRD42020204586).Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Carducci, B., et al. (2021). "Zinc supplementation for improving pregnancy and infant outcome." Cochrane Database of Systematic Reviews(3).
	- Background It has been suggested that low serum zinc levels may be associated with suboptimal outcomes of pregnancy, such as prolonged labour, atonic postpartum haemorrhage, pregnancy‐induced hypertension, preterm labour and post‐term pregnancies, although these associations have not yet been established. This is an update of a review first published in 1997 and subsequently updated in 2007, 2012 and 2015. Objectives 1. To compare the effects on maternal, fetal, neonatal and infant outcomes in healthy pregnant women receiving zinc supplementation versus no zinc supplementation, or placebo.
2. To assess the above outcomes in a subgroup analysis reviewing studies performed in women who are, or are likely to be, zinc‐deficient. Search methods For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov , the WHO International Clinical Trials Registry Platform ( ICTRP ) (3 July 2020), and reference lists of retrieved studies. Selection criteria Randomised trials of zinc supplementation versus no zinc supplementation or placebo administration during pregnancy, earlier than 27 weeks' gestation. We excluded quasi‐randomised controlled trials. We intended to include studies presented only as abstracts, if they provided enough information or, if necessary, by contacting authors to analyse them against our criteria; we did not find any such studies. Data collection and analysis Three review authors applied the study selection criteria, assessed trial quality and extracted data. When necessary, we contacted study authors for additional information. We assessed the certainty of the evidence using GRADE. Main results For this update, we included 25 randomised controlled trials (RCTs) involving over 18,000 women and their babies. The overall risk of bias was low in half of the studies. The evidence suggests that zinc supplementation may result in little or no difference in reducing preterm births (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.74 to 1.03; 21 studies, 9851 participants; low‐certainty evidence). Further, zinc supplementation may make little or no difference in reducing the risk of stillbirth (RR 1.22, 95% CI 0.80 to 1.88; 7 studies, 3295 participants; low‐certainty evidence), or perinatal deaths (RR 1.10, 95% CI 0.81 to 1.51; 2 studies, 2489 participants; low‐certainty evidence). It is unclear whether zinc supplementation reduces neonatal death, because the certainty of the evidence is very low. Finally, for other birth outcomes, zinc supplementation may make little or no difference to mean birthweight (MD 13.83, 95% CI ‐15.81 to 43.46; 22 studies, 7977 participants; low‐certainty evidence), and probably makes little or no difference in reducing the risk of low birthweight (RR 0.94, 95% CI 0.79 to 1.13; 17 studies, 7399 participants; moderate‐certainty evidence) and small‐for‐gestational age babies when compared to placebo or no zinc supplementation (RR 1.02, 95% CI 0.92 to 1.12; 9 studies, 5330 participants; moderate‐certainty evidence). We did not conduct subgroup analyses, as very few studies used normal zinc populations. Authors' conclusions There is not enough evidence that zinc supplementation during pregnancy results in improvements in maternal or neonatal outcomes. Future research to address ways of improving the overall nutritional status of pregnant women, particularly in low‐income regions, and not looking at zinc in isolation, should be an urgent priority. Plain language summary Zinc supplementation for improving pregnancy and infant outcome What is the issue? In low‐ and middle‐income countries, many women have poor diets and are deficient in key micronutrients that are required for good health. This is especially concerning during pregnancy, when energy and nutrient needs are greater for both the mother and the growing baby. Zinc plays a critical role in normal growth and development. Deficiency in zinc could lead to adverse health outcomes, such as being born too soon or too small. This is an update of a r view first published in 1997 and subsequently updated in 2007, 2012 and 2015. Why is this important? Although severe zinc deficiency is rare, it is estimated that mild‐to‐moderate deficiency is common in several regions of the world. Studies of human pregnancy and zinc supplementation, including those from low‐ and middle‐income countries, have failed to document a consistent beneficial effect on fetal growth, length of gestation, and early newborn survival. What evidence did we find? We searched for studies in July 2020. This updated review now includes 25 randomised controlled trials, involving over 18,000 women and their babies. We found that zinc supplementation in pregnancy may make little to no difference in reducing the risk of preterm births, stillbirths, or deaths around the time of birth, when compared to no zinc supplementation or placebo. Zinc supplementation may make little or no difference to the birthweight of babies, and probably makes little or no difference to the number of babies born either with a low birthweight or small for their gestational age, when compared with no zinc supplementation, or with giving a placebo. We cannot be sure whether zinc supplementation reduces death in newborns, because the certainty of the evidence is very low. What does this mean? There is not enough evidence that zinc supplementation during pregnancy results in better outcomes for women and their babies. Finding ways to improve women's overall nutritional status, particularly in low‐income areas, will do more to improve the health of mothers and babies than supplementing pregnant women with zinc alone. This should be an urgent research priority for the future.

Caresia-Aróztegui, A. P., et al. (2019). "18 F-FDG PET/CT in locally advanced cervical cancer: A review." Revista espanola de medicina nuclear e imagen molecular 38(1): 59-68.
	Cervical cancer is the second most common gynecological cancer worldwide. In locally advanced cervical cancer, 18 F-FDG PET/CT has become important in the initial staging, particularly in the detection of nodal and distant metastasis, aspects with treatment implications and prognostic value. The aims of this study were to review the role of 18 F-FDG PET/CT in uterine cervical cancer, according to the guidelines of the main scientific institutions (FIGO, NCCN, SEGO, SEOM, ESGO, and ESMO) and its diagnostic accuracy compared to conventional radiological techniques, as well as to review the acquisition protocol and its utility in radiotherapy planning, response assessment and detection of recurrence. (Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Carey Erin, T., et al. (2022). "Rationale and design of a multicenter randomized clinical trial of vestibulodynia: understanding pathophysiology and determining appropriate treatments (vestibulodynia: UPDATe)." Annals of medicine 54(1): 2885-2897.
	Background: Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.g. irritable bowel syndrome, temporomandibular disorder, and fibromyalgia syndrome) that affect remote body regions. Here, we describe the rationale and design of an NIH-funded multicenter clinical trial comparing the effectiveness of topical and/or systemic medication for alleviating pain and normalizing pain- relevant biomarkers among women with VBD-p and VBD-c.; Methods: Participants will be randomly assigned to one of four parallel arms: peripheral treatment with 5% lidocaine + 0.5 mg/ml 0.02% oestradiol compound cream + oral placebo pill, 2) central treatment with the tricyclic antidepressant nortriptyline + placebo cream, 3) combined peripheral cream and central pill treatments, or 4) placebo cream and placebo pill. The treatment phase will last 16 weeks, with outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). First, we will compare the efficacy of treatments in alleviating pain using standardized tampon insertion with a numeric rating scale and self-reported pain on the short form McGill Pain Questionnaire. Next, we will compare the efficacy of treatments in improving perceived physical, mental, and sexual health using standardized questionnaires. Finally, we will measure cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing, and determine the ability of these biomarkers to predict treatment response.; Conclusion: This is the first multicenter randomized controlled trial to evaluate the efficacy of peripherally and centrally acting medications currently used in clinical practice for treating unique VBD subtypes based on distinct clinical and biological signatures.; Administrative Information: Vestibulodynia UPDATe is a multi-centre, two-by-two factorial designed randomized, double-blind, placebo-controlled trial registered at clinical trials.gov (NCT03844412). This work is supported by the R01 HD096331 awarded to Drs. Nackley, Rapkin, Geller and Carey by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).Key messagesPeripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs.This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles.We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches.

Carlo, R. and P. Francesca (2022). "Mininvasive Cytoreduction Surgery plus HIPEC for Epithelial Ovarian Cancer: A Systematic Review."
	
Carmichael Samuel, P., et al. (2022). "Regenerative Medicine Therapies for Prevention of Abdominal Adhesions: A Scoping Review." The Journal of surgical research 275: 252-264.
	Introduction: Globally, abdominal adhesions constitute a significant burden of morbidity and mortality. They represent the commonest complication of abdominal operations with a lifelong risk of multiple pathologies, including adhesive small bowel obstruction, female infertility, and chronic pain. Adhesions represent a problem of the entire abdomen, forming at the time of injury and progressing through multiple complex pathways. Clinically available preventative strategies are limited to barrier technologies. Significant knowledge gaps persist in the characterization and mitigation of the involved molecular pathways underlying adhesion formation. Thus, the objectives of this scoping review are to describe the known molecular pathophysiology implicated in abdominal adhesion formation and summarize novel preclinical regenerative medicine preventative strategies for potential future clinical investigation.; Methods: A literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews. Included peer-reviewed publications were published within the last 5 y and contained in vivo preclinical experimental studies of postoperative adhesions with the assessment of underlying mechanisms of adhesion formation and successful therapy for adhesion prevention. Studies not involving regenerative medicine strategies were excluded. Data were qualitatively synthesized.; Results: A total of 1762 articles were identified. Of these, 1001 records were excluded by the described screening criteria. Sixty-eight full-text articles were evaluated for eligibility, and 11 studies were included for review.; Conclusions: Novel and reliable preventative strategies are urgently needed. Recent experimental data propose novel regenerative medicine targets for adhesion prevention. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Carneiro, L., et al. (2023). "Improving the well-being of cancer hospitalized patients: SENTIR meditation program." Confinia Cephalalgica et Neurologica 33(2): e2023010.
	Background and aim: The present work aims to develop, implement, and evaluate the effectiveness of a health/wellness promotion program, based on mindfulness meditation, sensory stimulation and virtual reality, with oncology patients in hospitals. Method(s): We developed an intervention study, with pre and post-test quantitative assessment, complemented with qualitative data. The intervention included six personalized sessions combining guided meditation, sensory stimulation, and virtual reality. Twelve cancer patients participated (83.3% female) with a mean age of 33.7 years (SD= +/-13.0) receiving treatment at a Cancer Treatment Hospital. Physiological (heart rate, blood pressure and oxygen saturation), and psychological parameters (DASS21) were used. Result(s): The comparison of the physiological parameters, before and after the sessions, revealed a statistically significant increase in oxygen saturation (p=0.03) after the first session. Regarding the levels of anxiety, stress, and depression, they significantly decreased (p<0.01) after the intervention. Qualitative data reinforced these positive results. Conclusion(s): The implemented intervention proved to be effective in reducing psychological vulnerability and partially effective in physiological measures. It is concluded that the program promotes the well-being of cancer patients in a hospitalized situation, favoring better coping with the disease.Copyright © Mattioli 1885.

Carnero, K. G. and P. W. Gundling (2021). "Effect of home pelvic floor muscle training using mobile app in Primipara with stress incontinence." European journal of integrative medicine 48.
	Introduction: Stress incontinence (SUI) is a common disease among women. It is the most frequent pelvic floor dysfunction, defined involuntary loss of urine during effort or exertion. Epidemiological studies imply that especially the first pregnancy and parturition are associated with a higher risk of developing stress incontinence. Conservative first‐line treatment includes pelvic floor muscle training (PFMT), the long‐term effectiveness of which is apparently associated with lifelong exercise. eHealth, the use of mobile information and communication technology for health issues, is being discussed to improve adherence and facilitate the implementation of exercise programs in everyday life, which should lead to an improved quality of life. The aim of this study is to evaluate the effect of app‐supported home based PFMT on the quality of life and adherence of women. Method: Randomized controlled trial with two groups of six women each with home based PFMT for six weeks. One group with and one without app support. Data from both groups were evaluated at the beginning and end of the training weeks using validated questionnaires for improvement in the severity of symptoms (ICIQ‐UI SF questionnaire), for changes in quality of life (ICIQ‐LUTSqol questionnaire) and to measure the subjective benefit and satisfaction with treatment as well as willingness (BSW). Results: At follow‐up, the group that trained with the app, reported a statistically significant reduction in symptom severity (MRang = 4.5), z = ‐ 2.207, p = 0.03, r = 0.6, and their quality of life scores captured a relevant improvement, (MRang = 15.), z = ‐ 2.232, p = 0.03, r = 0.6. The groups were significantly different for both outcome measures. Women in the control group also had a significant increase in condition‐specific quality of life but no decrease in the severity of their symptoms. Conclusion: Home‐based PFMT using a mobile app program seems to have a positive effect on the symptoms and quality of life of women with stress incontinence after vaginal delivery and may have an impact on the adherence of the training program. Keywords: pelvic floor muscle training, ehealth, stress incontinence, primipara, adherence, quality of life

Carolin, S., et al. (2023). "Does menopausal hormone therapy have a preventive impact on menopausal depression? A systematic review."
	
Caroline Cristine, A., et al. (2022). "The Effects of Polyphenol on Insulin Resistance and Hormonal Parameters on Women With Polycystic Ovary Syndrome: a Systematic Review and Meta - Analysis of Randomized Controlled Trials." PROSPERO International prospective register of systematic reviews.
	
Carolyn, E., et al. (2022). "Anti-obesity medications for Polycystic Ovary Syndrome."
	
Carosso, A. R., et al. (2022). "Expectant Management Before In vitro Fertilization in Women Aged 39 or Above and Unexplained Infertility Does Not Decrease Live Birth Rates Compared to Immediate Treatment." Reproductive Sciences 29(4): 1232-1240.
	Unexplained infertile couples can have further expectant management before starting assisted reproductive treatments. However, ovarian reserve and in vitro fertilization (IVF) outcomes rapidly decline after 39 years or more. It is thus important to clarify whether a waiting policy is also appropriate for women of advanced age. Couples who had access to a waiting list for approximately 1 year before receiving reimbursed public IVF were compared with those paying for access to immediate treatment. To allow for comparisons between these two strategies, we followed up couples who opted to pay for 1 year after the last embryo transfer from their first cycle. We calculated the proportion of live births in both groups and compared these using logistic regression models and a two-sample Z test for equality of proportions. Six hundred thirty-five couples were evaluated. Out of 359 couples in the immediate group, 70 (19.5%) had a live birth of which 11 after natural conception and 59 after IVF. Out of 276 couples in the waiting group, 57 (20.7%) had a live birth of which 37 after natural conception and 20 after IVF. There was no statistically significant difference between the two strategies in terms of the crude cumulative live birth rate (cLBR). The adjusted odds ratio of 0.69 (95%CI:0.39-1.22) did not change this conclusion as our sensitivity analyses. The cLBR for the 'waiting before IVF' and the 'immediate' strategies were similar. Further studies are needed to better characterize couples affected by unexplained infertility in order to individualize treatment strategies.Copyright © 2021, Society for Reproductive Investigation.

Carpenter Janet, S., et al. (2021). "A Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) investigation of self-reported menopausal palpitation distress." Journal of Women's Health 30(4): 533-538.
	Background: Study to describe the degree of menopausal palpitation distress and its demographic, clinical, symptom, and quality-of-life (QOL) correlates. Analysis of existing, baseline, data from peri- and postmenopausal women, 42 to 62 years of age, who participated in the Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) clinical trials testing interventions for vasomotor symptoms (n = 759). Up to 46.8% of menopausal women report having palpitations, yet the symptom is relatively understudied. Little is known about palpitation distress or its correlates. Materials and Methods: Degree of distress from "heart racing or pounding" was self-reported over the past two weeks as "not at all," "a little bit," "moderately," "quite a bit," or "extremely." Other measures included self-report forms, clinic-verified body mass index (BMI), vasomotor symptom diaries, and validated symptom and QOL tools. Results: The percentage who reported palpitation distress was 19.6%, 25.2%, and 33.5% in the three trials or 25.0% overall. In multivariate analysis, the odds of reporting palpitation distress was lower in past smokers (odds ratio [OR] = 0.59 [95% confidence interval (CI) 0.38-0.90]) and current smokers (OR = 0.48 [0.27-0.87]) relative to never-smokers and lower with every 5 kg/m2 higher BMI (OR = 0.82 [0.69-0.98]).The odds of reporting palpitation distress was higher with every five point more severe insomnia (OR = 1.28 [1.05-1.54]), five point worse depressive symptoms (OR = 1.47 [1.11-1.95]), five point worse perceived stress (OR = 1.19 [1.01-1.39]), and one point worse menopausal QOL (OR = 1.29 [1.06-1.57]). Conclusions: Menopausal palpitation distress is common and associated with demographic, clinical, symptom, and QOL factors. Findings can be used for screening in clinical practice and to justify additional research on this understudied symptom. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Carpenter, J. S., et al. (2022). "MsFLASH analysis of diurnal salivary cortisol and palpitations in peri- and postmenopausal women." Menopause 29(2): 144-150.
	Objective:To evaluate the relationship between diurnal salivary cortisol patterns and distress from heart palpitations in midlife women. Method(s):We analyzed baseline data from 293 women who were eligible for a 3 x 2 factorial trial of exercise or yoga versus routine activity, and omega-3 fish oil versus placebo for vasomotor symptoms. Women self-collected salivary cortisol using swabs at four time points over 2 consecutive days and reported distress from heart racing or pounding during the past 2 weeks using a single item. Sample description and covariate data included demographics, clinical data, vasomotor symptom frequency from daily diaries, medication use, and validated questionnaires on depression, stress, and insomnia (Patient Health Questionnaire-8, Perceived Stress Scale, and Insomnia Severity index). Data were analyzed using descriptive statistics, chi-square and t tests, and repeated measure linear regression models. Result(s):Participants were on average 54.6 (SD = 3.6) years old, most were White (67%) postmenopausal (84%), and 26% reported distress related to palpitations. In adjusted models, the morning (wake plus 30-min) geometric mean daily salivary cortisol concentrations were significantly more blunted in those with distress from palpitations compared with those without distress (P <= 0.03). When all covariates were controlled, distress from palpitations was the sole significant predictor of wake plus 30-minute cortisol (-0.25 [-0.45 to -0.04], P = 0.02). Conclusion(s):Palpitations among midlife women may be associated with blunted morning cortisol, and this relationship is not explained by demographics, clinical variables, vasomotor symptoms, medications, depression, stress, or insomnia.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.

Carralero-Martínez, A., et al. (2021). "Efficacy of capacitive resistive monopolar radiofrequency in the physiotherapeutic treatment of chronic pelvic pain syndrome: study protocol for a randomized controlled trial." Trials 22(1): 356.
	Background: Chronic pelvic pain syndrome (CPPS) is a multifactorial disorder that affects 5.7% to 26.6% of women and 2.2% to 9.7% of men, characterized by hypersensitivity of the central and peripheral nervous system affecting bladder and genital function. People with CPPS have much higher rates of psychological disorders (anxiety, depression, and catastrophizing) that increase the severity of chronic pain and worsen quality of life. Myofascial therapy, manual therapy, and treatment of trigger points are proven therapeutic options for this syndrome. This study aims to evaluate the efficacy of capacitive resistive monopolar radiofrequency (CRMRF) at 448 kHz as an adjunct treatment to other physiotherapeutic techniques for reducing pain and improving the quality of life of patients with CPPS.; Methods: This triple-blind (1:1) randomized controlled trial will include 80 women and men with CPPS. Participants will be randomized into a CRMRF activated group or a CRMRF deactivated group and receive physiotherapeutic techniques and pain education. The groups will undergo treatment for 10 consecutive weeks. At the beginning of the trial there will be an evaluation of pain intensity (using VAS), quality of life (using the SF-12), kinesiophobia (using the TSK-11), and catastrophism (using the PCS), as well as at the sixth and tenth sessions.; Discussion: The results of this study will show that CRMRF benefits the treatment of patients with CPPS, together with physiotherapeutic techniques and pain education. These results could offer an alternative conservative treatment option for these patients.; Trial Registration: ClinicalTrials.gov NCT03797911 . Registered on 8 January 2019.

Carralero-Martínez, A., et al. (2022). "Efficacy of capacitive resistive monopolar radiofrequency in the physiotherapeutic treatment of chronic pelvic pain syndrome: A randomized controlled trial." Neurourology and Urodynamics 41(4): 962-972.
	Aim: To evaluate the efficacy of adjuvant, capacitive resistive monopolar radiofrequency (CRMRF, INDIBA) treatment at 448 kHz together with physiotherapeutic techniques compared to a sham treatment with the same techniques, for pain reduction and quality of life (QoL) improvements in patients with chronic pelvic pain syndrome (CPPS).; Methods: A triple-blind, randomized controlled trial (RCT) including patients with CPPS randomly allocated (1:1) to a CRMRF-activated group (intervention) or a CRMRF-deactivated one (control). Both groups received physiotherapeutic techniques and pain education weekly for 10 consecutive weeks. Data from a visual analogical scale and the SF-12 questionnaire were collected at trial commencement and repeated at the 5th and 10th sessions. Pain intensity was considered the main outcome. For the comparisons between variables, the χ 2 and Student's t test were used. Superiority was analyzed by estimating the mean change (95% confidence interval). Analysis was performed for the per-protocol and the intention-to-treat populations. The statistical significance level was set at p < 0.05.; Results: Eighty-one patients were included (67.9% women) with a mean age of 43.6 years (SD 12.9). CRMRF lessened pain scores by more than 2 points and improved QoL by 5 points. There were no relevant side effects and overall adherence to the treatment was 86.4%.; Conclusions: This is the first RCT that evaluates the efficacy of CRMRF (INDIBA) compared to a sham treatment, and demonstrates its superiority in decreasing pain and improving QoL. Such results may lead to greater prescribing of CRMRF when treating CPPS patients. (© 2022 Wiley Periodicals LLC.)

Carrera, M., et al. (2022). "Hysteroscopic metroplasty for the treatment of the dysmorphic uterus: A SWOT analysis." Frontiers in surgery 9: 1097248.
	INTRODUCTION: Dysmorphic uterus or T-shaped uterus is an increasingly frequent diagnosis among the infertile population that has been associated to worse reproductive results. Hysteroscopic metroplasty is a safe and simple procedure that can improve the reproductive outcomes in this group of patients, although the benefits of this procedure remains controversial due to the lack of adequate scientific evidence. OBJECTIVE: To analyze the hysteroscopic metroplasty using the SWOT (Strengths, Weaknesses, Opportunities and Threats) methodology. DATA SOURCES: An electronic search from inception each database up to December 2021 including the following databases was conducted: PubMed-MEDLINE, EMBASE, Web of Science, The Cochrane Library, and Google Scholar. METHODS OF STUDY SELECTION: Studies reporting outcomes of patients undergoing hysteroscopic metroplasty were included. TABULATION: Not applicable. INTEGRATION AND RESULTS: Clinical evidence from the included studies suggests an improvement in reproductive results after performing hysteroscopic metroplasty especially in women with recurrent pregnancy loss and previous infertility, but all of them have relevant methodological limitations. For this reason, benefits, risks and alternatives of this intervention should be considered with caution. CONCLUSIONS: Evidence from published data shows a probable association between dysmorphic uterus and poor reproductive outcomes. Hysteroscopic metroplasty in patients with dysmorphic uterus could improve pregnancy outcomes, but there is need of properly designed prospective controlled studies to determine the benefits of this technique.

Carrera, M., et al. (2022). "Effect of Hysteroscopic Metroplasty on Reproductive Outcomes in Women with Septate Uterus: Systematic Review and Meta-Analysis." Journal of Minimally Invasive Gynecology 29(4): 465-475.
	Objective: The aim of this systematic review with meta-analysis is to evaluate the impact of hysteroscopic metroplasty on adverse reproductive outcomes such as miscarriage, preterm birth, and fetal malpresentation in patients with history of infertility or previous poor obstetrical outcomes.; Data Sources: A systematic electronic search from inception each database up to April 2021 including the following databases was conducted: PubMed-MEDLINE, EMBASE, Web of Science, The Cochrane Library, the CGF Specialized Register of Controlled Trials, Google Scholar, and trial registries. A combination of the following keywords was used: uterine septum, septate uterus, congenital uterine malformation, class 2 uterus, class V uterus, metroplasty, hysteroscopic, pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, live birth, preterm birth, cesarean section, 'cesarean delivery, and fetal malpresentation.; Methods of Study Selection: Studies comparing reproductive outcomes between women undergoing hysteroscopic resection of the uterine septum and those with expectant management were included. Eligible population consisted of infertile women, women with poor obstetrical history, or women without previous pregnancy failures and a diagnosis of septate uterus.; Tabulation, Integration, and Results: The systematic electronic search retrieved 1076 studies; after elimination of duplicates, 688 titles and abstracts were screened, and 55 were assessed for eligibility. Eleven studies were included in the quantitative synthesis: one randomized controlled trial and 10 observational studies involving reproductive outcomes from 1589 patients with either complete or partial uterine septum. The pooled OR for miscarriage was 0.45, (95% CI, 0.22-0.90). When the analysis was performed considering subgroups according to the type of septum, pooled OR in complete septum subgroup was 0.16 (95% CI, 0.03-0.78), OR = 0.36 (95% CI, 0.19-0.71) in the partial septum subgroup and 0.58 (95% CI, 0.20-1.67) in those studies not differentiating between complete or partial septum. No significant differences were found between the 2 groups in OR of clinical pregnancy, term live birth, or risk of cesarean delivery. There was a significant decrease in the frequency of preterm birth in patients who underwent partial septum resection (OR = 0.30, 95% CI, 0.11-0.79). This difference was detected neither in patients with complete septum nor in studies not differentiating between partial or complete septum. The risk of fetal malpresentation was also significantly reduced (OR = 0.32, 95% CI, 0.16-0.65).; Conclusion: The results of the present meta-analysis support that hysteroscopic metroplasty is effective in reducing the risk of miscarriage in patients with complete or partial uterine septum, although these data should be confirmed with a well-designed randomized controlled trial. (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Carrillo, T., et al. (2023). "Impact of Continuous Estroprogestin Treatment on Circulating Microparticle Levels in Deep Endometriosis Patients." International Journal of Molecular Sciences 24(14).
	There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.

Carter, F., et al. (2023). "Hypocaloric Dietary Intervention Reduces Excessive Follicle Recruitment In Women With PCOS." Journal of the Endocrine Society 7(Supplement 1): A865.
	Introduction: Disordered antral follicle development in polycystic ovary syndrome (PCOS) is characterized by excessive recruitment, early or absence of follicle selection and decreased incidence of dominance and ovulation. Whether lifestyle interventions aimed at weight loss improve defects in antral folliculogenesis to promote ovulation in women with PCOS and comorbid obesity is unknown. Objective(s): To test the hypothesis that a hypocaloric dietary intervention improves antral follicle development in a subset of women with PCOS and obesity as evidenced by decreased recruitment, and increased selection, dominance, and ovulation. Method(s): Preliminary analysis of women with PCOS and obesity (7 out of 20) who participated in a hypocaloric dietary intervention was conducted. The study protocol consisted of every-other-day visits to a clinical research center for ovarian ultrasonography and venipuncture over a 4-week baseline period (pre-intervention), followed by a 12-week commercial hypocaloric dietary meal plan intervention aimed at achieving 1-2 lbs of weight loss per week. Anthropometry, DEXA, hirsutism scoring, and oral glucose tolerance testing were conducted at baseline and during the final month of the intervention in the follicular phase. The number and diameter of all follicles >= 2 mm at each visit were recorded offline, and individual follicles >= 7 mm were tracked using the Identity Method throughout the 16-weeks. Clinical, morphologic, and endocrine markers were compared using paired t-tests pre- vs. post-intervention, and linear mixed models assessed changes in recruitment, selection, dominance, and ovulation. Result(s): The hypocaloric dietary intervention resulted in mean weight loss of 8.8 +/- 2.9% and significant reductions in waist (-13 +/- 9 cm) and hips (-10 +/- 3 cm) circumference, body mass index (-3.4 +/- 1.4 kg/m2 ), and percent total body fat (-1.5 +/- 1.3%; all p<0.02). Glucoregulatory status, menstrual cycle lengths, reproductive hormone (LH, FSH, E2, P4, TT, AMH) concentrations, and hirsutism scores did not differ pre- vs. post-intervention. The number of follicle recruitment events decreased with percent weight loss during the intervention (p=0.01), as did the average number of follicles recruited per cohort (p=0.01). By contrast, the frequency of follicle selection, dominance, and ovulation did not change with weight loss (p>0.05). Higher pre-intervention LH was associated with fewer follicles recruited per cohort during the intervention (p=0.03). No other metabolic or endocrine marker was correlated with changes in follicular events. Conclusion(s): Clinically meaningful weight loss induced by a hypocaloric dietary intervention resulted in improvements in early stages of antral follicle development in women with PCOS, albeit these changes did not affect ovulatory follicle dynamics or the frequency of ovulation.

Carter, J., et al. (2021). "GOG 244 - The Lymphedema and Gynecologic cancer (LeG) study: The impact of lower-extremity lymphedema on quality of life, psychological adjustment, physical disability, and function." Gynecologic Oncology 160(1): 244-251.
	OBJECTIVE: To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. METHODS: The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT]), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%. RESULTS: In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms. CONCLUSIONS: LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.

Carter, P., et al. (2020). "Management of mesh complications following surgery for stress urinary incontinence or pelvic organ prolapse: a systematic review." BJOG : an international journal of obstetrics and gynaecology 127(1): 28-35.
	Background: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh-related complications.; Objective: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline 'Urinary incontinence (update) and pelvic organ prolapse in women: management'.; Search Strategy: Search strategies were developed for each indication for referral.; Selection Criteria: Relevant interventions included complete or partial mesh removal, mesh division, and non-surgical treatments such as vaginal estrogen.; Data Collection and Analysis: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted.; Main Results: Twenty-four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely.; Conclusions: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh-related complications. Robust data are needed so that mesh complications can be managed effectively in the future.; Tweetable Abstract: Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable. (© 2019 Royal College of Obstetricians and Gynaecologists.)

Carter, T., et al. (2019). "The effectiveness of exercise-based interventions for preventing or treating postpartum depression: a systematic review and meta-analysis." Archives of Women's Mental Health 22(1): 37-53.
	Postpartum depression can have detrimental effects on both a mother's physical and mental health and on her child's growth and emotional development. The aim of this study is to assess the effectiveness of exercise/physical activity-based interventions in preventing and treating postpartum depressive symptoms in primiparous and multiparous women to the end of the postnatal period at 52 weeks postpartum. Electronic databases were searched for published and unpublished randomised controlled trials of exercise/physical activity-based interventions in preventing and treating depressive symptoms and increasing health-related quality of life in women from 4 to 52 weeks postpartum. The results of the studies were meta-analysed and effect sizes with confidence intervals were calculated. The Grading of Recommendations Assessment and Development and Evaluation (GRADE) system was used to determine the confidence in the effect estimates. Eighteen trials conducted across a range of countries met the inclusion criteria. Most of the exercise interventions were aerobic and coaching compared to usual care, non-intervention and active controls. Small effect sizes of exercise-based interventions in reducing depressive symptoms were observed collectively and the quality of evidence was low across the individual studies. Although exercise-based interventions could create an alternative therapeutic approach for preventing major depression in postpartum women who experience subthreshold elevated depressive symptoms, the clinical effectiveness and the cost-effectiveness of exercise-based and physical activity interventions need to be better established. There is a need for further more rigorous testing of such interventions in high-quality randomised controlled trials against active control conditions before large-scale roll-out of these interventions in clinical practice is proposed.

Caruso, G., et al. (2023). "Vulvar Paget's Disease: A Systematic Review of the MITO Rare Cancer Group." Cancers 15(6).
	Vulvar Paget's disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1-2% of all vulvar neoplasms and mainly affects post-menopausal women. The clinical presentation is usually non-specific and mimics chronic erythematous skin lesions; therefore, the diagnosis is often difficult and delayed. Although VPD is typically diagnosed at a locally advanced stage and has a high recurrence rate, the prognosis is overall favorable with a 5-year survival of nearly 90%. Due to the limited and poor-quality evidence, there is no global consensus on optimal management. Therefore, we performed a systematic review of the literature through the main electronic databases to deepen the current knowledge of this rare disease and discuss the available treatment strategies. Wide surgical excision is recommended as the standard-of-care treatment and should be tailored to the tumor position/extension and the patient's performance status. The goal is to completely remove the tumor and achieve clear margins, thus reducing the rate of local recurrences. Non-surgical treatments, such as radiotherapy, chemotherapy, and topical approaches, can be considered, especially in the case of unresectable and recurrent disease. In the absence of clear recommendations, the decision-making process should be individualized, also considering the new emerging molecular targets, such as HER2 and PD-L1, which might pave the way for future targeted therapies. The current review aims to raise awareness of this rare disease and encourage international collaboration to collect larger-scale, high-quality evidence and standardize treatment.

Caruso, G., et al. (2023). "Dose-dense neoadjuvant chemotherapy before radical surgery in cervical cancer: a retrospective cohort study and systematic literature review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Objective: To evaluate the role of dose-dense neoadjuvant chemotherapy followed by radical hysterectomy in reducing adjuvant radiotherapy in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB1-IB2/IIA1 cervical cancer with disrupted stromal ring and as an alternative to concurrent chemoradiotherapy in FIGO 2018 stages IB3/IIA2.; Methods: This was a retrospective cohort study including patients with FIGO 2018 stage IB1-IIA2 cervical cancer undergoing dose-dense neoadjuvant chemotherapy at the European Institute of Oncology in Milan, Italy between July 2014 and December 2022. Weekly carboplatin (AUC2 or AUC2.7) plus paclitaxel (80 or 60 mg/m 2 , respectively) was administered for six to nine cycles. Radiological response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. The optimal pathological response was defined as residual tumor ≤3 mm. Kaplan-Meier curves were used to estimate survival rates. A systematic literature review on dose-dense neoadjuvant chemotherapy before surgery for cervical cancer was also performed.; Results: A total of 63 patients with a median age of 42.8 years (IQR 35.3-47.9) were included: 39.7% stage IB-IB2/IIA1 and 60.3% stage IB3/IIA2. The radiological response was as follows: 81% objective response rate (17.5% complete and 63.5% partial), 17.5% stable disease, and 1.6% progressive disease. The operability rate was 92.1%. The optimal pathological response rate was 27.6%. Adjuvant radiotherapy was administered in 25.8% of cases. The median follow-up for patients who underwent radical hysterectomy was 49.7 months (IQR 16.8-67.7). The 5-year progression-free survival and overall survival were 79% (95% CI 0.63 to 0.88) and 92% (95% CI 0.80 to 0.97), respectively. Fifteen studies including 697 patients met the eligibility criteria for the systematic review. The objective response rate, operability rate, and adjuvant radiotherapy rate across studies ranged between 52.6% and 100%, 64% and 100%, and 4% and 70.6%, respectively.; Conclusions: Dose-dense neoadjuvant chemotherapy before radical surgery could be a valid strategy to avoid radiotherapy in stage IB1-IIA2 cervical cancer, especially in young patients desiring to preserve overall quality of life. Prospective research is warranted to provide robust, high-quality evidence.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Caruso, G., et al. (2022). "Systematic lymph node dissection during interval debulking surgery for advanced epithelial ovarian cancer: a systematic review and meta-analysis." Journal of Gynecologic Oncology 33(5): e69.
	Objective: To evaluate the efficacy and safety of systematic lymph node dissection (SyLND) at the time of interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC).; Methods: Systematic literature review of studies including AEOC patients undergoing SyLND versus selective lymph node dissection (SeLND) or no lymph node dissection (NoLND) after neoadjuvant chemotherapy (NACT). Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included severe postoperative complications, lymphocele, lymphedema, blood loss, blood transfusions, operative time, and hospital stay.; Results: Nine retrospective studies met the eligibility criteria, involving a total of 1,660 patients: 827 (49.8%) SyLND, 490 (29.5%) SeLND, and 343 (20.7%) NoLND. The pooled estimated hazard ratios (HR) for PFS and OS were, respectively, 0.88 (95% confidence interval [CI]=0.65-1.20; p=0.43) and 0.80 (95% CI=0.50-1.30; p=0.37). The pooled estimated odds ratios (ORs) for severe postoperative complications, lymphocele, lymphedema, and blood transfusions were, respectively, 1.83 (95% CI=1.19-2.82; p=0.006), 3.38 (95% CI=1.71-6.70; p<0.001), 7.23 (95% CI=3.40-15.36; p<0.0001), and 1.22 (95% CI=0.50-2.96; p=0.67).; Conclusion: Despite the heterogeneity in the study designs, SyLND after NACT failed to demonstrate a significant improvement in PFS and OS and resulted in a higher risk of severe postoperative complications.; Trial Registration: PROSPERO Identifier: CRD42022303577.; Competing Interests: No potential conflict of interest relevant to this article was reported. (© 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Caruso, S., et al. (2023). "Vaginal health and quality of sexual life of postmenopausal women on hyaluronic acid and Biosaccharide Gum-1 vaginal gel." Taiwanese Journal of Obstetrics & Gynecology 62(5): 702-708.
	Objective: To evaluate the efficacy of daily vaginal gel containing hyaluronic acid (HA) and Biosaccharide Gum-1 (BG-1) on vulvovaginal atrophy (VVA) and on sexual function and quality of life (QoL).; Materials and Methods: One hundred-four postmenopausal women with VVA were enrolled in the nonrandomized comparison cohort study. Of them, 50 women on HA/BG-1 participated in the study group and 54 women on lubricants/moisturizers on-demand as a control group. The primary endpoint was the efficacy of the vaginal gel on VVA evaluated by the Vaginal Health Index (VHI) score. Secondary endpoints included sexual behavior by the self-administered female sexual function index (FSFI) questionnaire, and quality of life (QoL), by the Short Form-36 questionnaire (SF-36).; Results: All symptoms of AVV improved after 12 weeks of treatment in women on HA/BG-1. The VMI, although improved at the 12-week follow-up compared to baseline, it connoted a low estrogenic stimulation value. Sexual function improved significantly in women on HA/BG-1. Moreover, women reported a significant improvement in the somatic aspects of QoL. No benefits were obtained by the women in the control group.; Conclusions: Treatment with HA/BG-1 could have used in postmenopausal women who complain of vaginal dryness. The amelioration of VVA-related signs could improve sexual function and QoL.; Competing Interests: Declaration of competing interest None. (Copyright © 2023. Published by Elsevier B.V.)

Carvalho, V., et al. (2023). "Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on seizure frequency of postmenopausal women with epilepsy-A systematic review." European journal of neurology 30(9): 2884-2898.
	Background and Purpose: Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE.; Methods: PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool.; Results: Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results.; Conclusions: There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population. (© 2023 European Academy of Neurology.)

Casado-Adam, A., et al. (2022). "The Role of Intraperitoneal Intraoperative Chemotherapy with Paclitaxel in the Surgical Treatment of Peritoneal Carcinomatosis from Ovarian Cancer-Hyperthermia versus Normothermia: A Randomized Controlled Trial." Journal of Clinical Medicine 11(19).
	Background: The treatment of ovarian carcinomatosis with cytoreductive surgery and HIPEC is still controversial. The effect and pharmacokinetics of the chemotherapeutics used (especially taxanes) are currently under consideration.; Methods: A phase II, simple blind and randomized controlled trial (NTC02739698) was performed. The trial included 32 patients with primary or recurrent ovarian carcinomatosis undergoing cytoreductive surgery (CRS) and intraoperative intraperitoneal chemotherapy with paclitaxel (PTX): 16 in hyperthermic (42-43 °C) and 16 in normothermic (37 °C) conditions. Tissue, serum and plasma samples were taken in every patient before and after intraperitoneal chemotherapy to measure the concentration of PTX. To analyze the immunohistochemical profile of p53, p27, p21, ki67, PCNA and caspase-3 and the pathological response, a scale of intensity and percentage of expression and a grouped Miller and Payne system were used, respectively. Perioperative characteristics and morbi-mortality were also analyzed.; Results: The main characteristics of patients, surgical morbidity, hemotoxicity and nephrotoxicity were similar in both groups. The concentration of paclitaxel in the tissue was higher than that observed in plasma and serum, although no statistically significant differences were found between the two groups. No statistically significant association regarding pathological response and apoptosis (caspase-3) between both groups was proved. There were no statistically significant differences between the normothermic and the hyperthermic group for pathological response and apoptosis.; Conclusions: The use of intraperitoneal PTX has proven adequate pharmacokinetics with reduction of cell cycle and proliferation markers globally without finding statistically significant differences between its administration under hyperthermia versus normothermia conditions.

Casalderrey-Rodriguez, M., et al. (2022). "Effectiveness of physiotherapy for pain management in primary dysmenorrhoea." Clinica e Investigacion en Ginecologia y Obstetricia 49(3): 100757.
	The aim of this study is to evaluate the efficacy of different physical therapy modalities for the treatment of primary dysmenorrhoea. Method(s): A review of the current scientific literature was conducted by searching during January and February 2021 the databases: PubMed, SPORTDiscus, Medline, CINAHL, and Web of Science. The MeSH descriptors used were: "Dysmenorrhea", "Exercise Therapy" and "Physical Therapy Modalities". Result(s): Thirteen studies were included and analysed, and were grouped for better analysis according to the type of intervention: therapeutic exercise, transcutaneous electrostimulation and thermotherapy, kinesiotape, connective tissue massage, dry needling, and acupuncture. The common variable in all the studies was the evaluation of the intensity of menstrual pain, which reduced when the different physical therapy modalities were applied. Conclusion(s): The physical therapy techniques proposed in the review seem to be an effective tool in the treatment of women with primary dysmenorrhoea. However, more studies are needed to analyse the long-term effects., El objetivo en este estudio es evaluar la eficacia de las diferentes modalidades de fisioterapia para el tratamiento de la dismenorrea primaria. Metodos: Se ha llevado a cabo una revision de la literatura cientifica actual mediante una busqueda durante enero y febrero de 2021 en las bases de datos: PubMed, SPORTDiscus, Medline, CINAHL y Web of Science. Los descriptores MeSH utilizados fueron: <>, <> y < >. Resultados: Se han incluido y analizado 13 estudios, que fueron agrupados para un mejor analisis segun el tipo de intervencion: ejercicio terapeutico, electroestimulacion transcutanea y termoterapia, kinesiotape, masaje de tejido conectivo, puncion seca y acupuntura. La variable comun en todos los estudios fue la evaluacion de la intensidad del dolor menstrual, el cual se redujo al aplicar las distintas modalidades de fisioterapia. Conclusion: Las tecnicas de fisioterapia planteadas en la revision parecen ser una herramienta efectiva en el tratamiento de mujeres con dismenorrea primaria. Sin embargo, se necesitan mas estudios que analicen los efectos a largo plazo.Copyright © 2022 Elsevier Espana, S.L.U.

Casarin, J., et al. (2021). "Music Therapy for Preoperative Anxiety Reduction in Women Undergoing Total Laparoscopic Hysterectomy: a Randomized Controlled Trial." Journal of Minimally Invasive Gynecology 28(9): 1618‐1624.e1611.
	Study Objective: To assess the superiority of a music therapy intervention (Music) vs usual care (Control) in reducing the preoperative anxiety of patients undergoing total laparoscopic hysterectomy (TLH) with nononcologic indications. Design: This was a 1:2 (Music vs Control) randomized controlled study. Setting: A teaching hospital. Patients: One hundred patients were available for the analysis: 30 and 70 in the Music and Control arms, respectively. Interventions: Perioperative music therapy pathway in patients undergoing TLH for benign disease. Measurements and Main Results: Anxiety was evaluated with the State‐Trait Anxiety Inventory Y Form (STAI‐Y) at different time points: at baseline and during preoperative, early postoperative, and late postoperative periods. Pathologic anxiety was defined as STAI‐Y state >45. Postoperative pain was registered using the visual analog scale. Women in the Music arm experienced lower anxiety levels (median STAI‐Y scores 38.0 vs 41.0; p = .002) during the preoperative period. STAI‐Y scores did not vary significantly by intervention at each subsequent time point. A significant difference between the groups (Music vs Control) was found in the proportion of women with pathologic anxiety during the preoperative (16.7% vs 37.2%; p = .04) and early postoperative periods (0% vs 12.9%; p = .04), whereas no significant difference between the groups was registered during the late postoperative period (6.6% vs 7.1%; p = .93). Postoperative pain intensity did not significantly differ between the groups at 1, 3, and 6 hours after surgery. Conclusions: Music therapy might be a viable complementary modality to usual surgical care in the gynecologic setting for its ability to significantly decrease preoperative anxiety in women undergoing TLH for benign conditions.

Casarin, J., et al. (2020). "Surgical treatment of large adnexal masses: a retrospective analysis of 330 consecutive cases." Minimally Invasive Therapy and Allied Technologies 29(6): 366-374.
	Introduction: In the present study, perioperative outcomes of laparoscopy (LPS) were compared to open surgery (OS) for the treatment of large adnexal masses (AM). Material(s) and Method(s): Retrospective observational cohort study. Data of consecutive patients who underwent ovarian cystectomy or salpingo-oophorectomy for large AM (diameter >=10 cm) at a referral minimally invasive gynecologic center were analyzed. Propensity score match (PSM) analysis was used to minimize covariate imbalances between the two groups. Result(s): Overall 330 patients, 285 (86.4%) LPSs and 45 (13.6%) OSs were included. PSM showed LPS (vs. OS) to be associated with less intraoperative blood loss (mL: 131.1 +/- 52.6 vs. 545.5 +/- 101.2; p =.007), shorter operative time (min: 84.8 +/- 77.9 vs. 123.7 +/- 70.1; p <.001), but higher rate of spillage (54.5% vs. 12.1%; p <.001). Among the LPS group, a positive correlation between AM size and both conversion to open surgery and need for mini-laparotomy was found (p <.05). Conclusion(s): An accurate patient selection, a dedicated workup, and an appropriate counselling are mandatory before LPS for large AM. The increased risks of intraoperative spillage associated with the minimally invasive approach should be acknowledged.Copyright © 2019 Society of Medical Innovation and Technology.

Casarramona, G., et al. (2022). "The efficacy and safety of luteal phase support with progesterone following ovarian stimulation and intrauterine insemination: A systematic review and meta-analysis." Frontiers in Endocrinology 13: 960393.
	The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following ovarian stimulation and intrauterine insemination treatment (OS-IUI) for unexplained or mild male infertility. Four additional studies were identified compared to the previous review in 2017. Twelve RCTs (2631 patients, 3262 cycles) met full inclusion criteria. Results from quantitative synthesis suggest that progesterone LPS after OS-IUI leads to higher live birth (RR 1.38, 95%CI [1.09, 1.74]; 7 RCTs, n=1748) and clinical pregnancy rates (RR 1.38, 95% CI [1.21, 1.59]; 11 RCTs, n=2163) than no LPS or placebo. This effect is specifically present in protocols using gonadotropins for OS-IUI (RR 1.41, 95%CI [1.17, 1.71]; 7 RCTs, n=1114), and unclear in protocols involving clomiphene citrate (RR 1.01, 95% CI [0.05, 18.94]; 2 RCTs, n=138). We found no effect of progesterone LPS on multiple pregnancy or miscarriage rates. No correlation between drug-dosage or duration of treatment and effect size was seen. Though our results suggest both benefit and safety of progesterone LPS in OS-IUI, evidence is of low to moderate quality and additional well-powered trials are still mandatory to confirm our findings and justify implementation in daily practice.; Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=292325, identifier CRD42021292325.; Competing Interests: FB is a Member of the external advisory board for Merck Serono and Ferring BV has received grants and personal fees outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Casarramona, Lalmahomed, Lemmen, Eijkemans, Broekmans, Cantineau and Drechsel.)

Casiano, E., et al. (2023). "Nonestrogen Therapies for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review." Obstetrics and Gynecology 142(3): 555-570.
	Objective: To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM).; Data Sources: MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators.; Methods of Study Selection: We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group.; Tabulation, Integration, and Results: Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO 2 ) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO 2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function.; Conclusion: Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.; Competing Interests: Financial Disclosure Alexandriah Alas reports receiving payment for expert testimony. Ethan Balk reports receiving funding from SGS for methodology consultation. Alexis A. Dieter reports that she received payment as an expert witness and research grants were paid to her institution. David R. Rahn received the grant support from the National Institutes of Health R01 AG047290; Bridge Award from American Association of Obstetricians and Gynecologists Foundation and American Board of Obstetrics and Gynecology; and the Patient-Centered Outcomes Research Institute. He also received an investigator-initiated award from Pfizer for provision of study drug (Premarin vaginal cream). The other authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Casiraghi, A., et al. (2023). "Long-term clinical and histological safety and efficacy of the CO2 laser for treatment of genitourinary syndrome of menopause: an original study." Climacteric 26(6): 605-612.
	Objective: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. Method(s): A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. Result(s): At 4 weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. Conclusion(s): This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. Clinical Trial Registration: ClinicalTrials.gov ID: NCT04868812 (release date: 27 April 2021).Copyright © 2023 International Menopause Society.

Cassani, C., et al. (2021). "Oral contraception use in BRCA gene mutation carriers: information for counselling in routine clinical practice." European Journal of Gynaecological Oncology 42(3): 441-449.
	The objective of this narrative review is to put risks and benefits for the use of oral contraception (OC) into perspective in counselling high-risk carriers of BRCA1 or BRCA2 gene mutations. We searched PubMed, Embase, and the Cochrane Library for studies that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of BRCA1/2 mutations. All studies concordantly demonstrated an inverse correlation between OC and ovarian cancer risk in BRCA mutated women. Regarding breast cancer risk, results are conflicting with some studies reporting a slightly increased risk associated with OC use, whereas others reveal no evidence of a significant association in carriers. Numerous potential cancer risk modifiers and the modern evolution of OC can partly explain these results. OC use may also reduce the risk of extra-ovarian cancers such as those of the colon and endometrium, as observed in the general population. BRCA1/2 carriers should always receive a sensible and patient-centered contraceptive counselling because current evidence does not support recommendation against OC use, taking into account the individual profile.Copyright ©2021 The Author(s). Published by IMR Press.

Castanon, E., et al. (2022). "Bayesian interpretation of immunotherapy trials with dynamic treatment effects." European Journal of Cancer 161: 79-89.
	Introduction: The mechanism of action of immune checkpoints inhibitors hinders the writing of rational statistical analysis plans for phase III randomised clinical trials (RCTs) because of their unpredictable dynamic effects. The purpose is to illustrate the advantages of Bayesian reporting of treatment efficacy analysis in immunotherapy RCTs, in contrast to frequentist reporting. Method(s): Fourteen RCTs (one with two pairwise comparisons) that failed to achieve their primary objective (overall survival, OS) were selected. These RCTs were reanalysed using Bayesian Cox models with dynamic covariate coefficients and time-invariant models. Result(s): The RCTs that met inclusion criteria were 7 lung cancer trials, various other tumours, with antiPD1, antiPDL1 or antiCTLA4 therapies. The minimum detectable effect (deltaS) was superior to the true benefit observed in all cases, in conditions of non-proportional hazards. Schoenfeld tests indicated the existence of PH assumption violations (p<0.05) in 6/15 cases. The Bayesian Cox models revealed a probability of benefit >79% in all the RCTs, with the therapeutic equivalence hypothesis unlikely. The OS curves diverged after a median of 9.1 months. Since the divergency, no non-proportionality was evinced in 13/15, while the Wald tests achieved p<0.05 in 12/15 datasets. In all cases, the Bayesian Cox models with dynamic coefficients detected fluctuations of the hazard ratio, and increased 2-year OS was the most likely hypothesis. Conclusion(s): We recommend progressively implementing Bayesian and dynamic analyses in all RCTs of immunotherapy to interpret and assess the credibility of frequentist results.Copyright © 2021 Elsevier Ltd

Castelo-Branco, C., et al. (2021). "Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence." Climacteric : the journal of the International Menopause Society 24(2): 109-119.
	A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of -0.694 in favor of iCR ( p < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort ( Hypericum perforatum [HP]) were given (-1.020 and -0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit-risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.

Castelo-Branco, C., et al. (2022). "Black cohosh efficacy and safety for menopausal symptoms. The Spanish Menopause Society statement." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(5): 379-384.
	Objective: The increasing interest in Western countries regarding phytotherapy use to treat menopause-related symptoms has led the Spanish Menopause Society (AEEM) to update its position statement performed in 2009 on the role of black cohosh ( Cimicifuga racemosa ) for the treatment of menopausal symptoms.; Material and Methods: A panel of experts from both clinical and research backgrounds were assembled to investigate the best available evidence. Selected studies were obtained by an electronic search, including the Internet search engines MEDLINE-Pubmed (1997-December 2021) and the Cochrane Controlled Trials Register.; Results: Most of the well-designed studies published in recent years have been conducted with the isopropanolic extract of black cohosh/ C. racemosa . The most common dose is 40 mg/day capable of achieving a significant reduction in hot flushes (particularly in women with intense hot flushes) and an improvement in mood. Used at the recommended doses, C. racemose produces no significant adverse reactions.; Conclusion: Black cohosh is an effective and safe treatment option for the relieving of vasomotor symptoms. Finally, further clinical trials with sufficient patient enrollment and longer study follow-up are needed.

Castro, R. A., et al. (2021). "Vaginal Sacrospinous Ligament Fixation Using Tissue Anchoring System Versus a Traditional Technique for Women With Apical Vaginal Prolapse: A Randomized Controlled Trial." Female Pelvic Medicine & Reconstructive Surgery 27(1): e215-e222.
	OBJECTIVE: The aim of the study was to compare the efficacy and safety of the tissue anchoring system (TAS) kit versus the traditional technique for sacrospinous ligament fixation (SSLF) to treat apical vaginal wall prolapse. METHODS: A prospective randomized controlled multicenter study of noninferiority involving women with apical prolapse (C-point≥+1). Primary outcome is surgical success as C-point≤-4 at the 1-year follow-up. Secondary outcomes are success according to the composite criteria as C-point≤-4, Ba-point ≤0, and Bp-point ≤0; POP-Q measures of the vaginal compartments; intraoperative findings, complications; reoperation rate; hospital stay; and quality of life and sexual functioning (PISQ-12). It was estimated that 50 individuals per group would yield an 80% power for a noninferiority margin of 15%. RESULTS: Ninety-nine women were randomized: TAS (n = 55) and traditional SSLF (n = 44). The groups' preoperative data were similar. Drop-out rate was 11% for 12-month follow-up. Success rates were 90% for TAS and 80% for traditional SSLF (P = 0.0006; absolute difference, 9.8%; 90% confidence interval, -5.2 to 24.8) with the sensivity analyses per-protocol considering only the subjects that completed the 12-month follow-up and 80% versus 73%, respectively (P = 0.0048; absolute difference, 7.3%; 90% confidence interval, -9.6 to 24.2) by sensivity analyses considering the total number of participants randomized and treated with drop-out cases as failure. We detected shorter intraoperative time to dissect and reach the SSL, shorter length of hospitalization, lower rates of urinary tract infection, and lower pain scores in the first 30 days postoperative in the TAS compared with the traditional SSLF groups (P < 0.05). There was an improvement in women's quality of life that did not differ between groups. CONCLUSIONS: The modified technique of SSLF using the TAS kit is noninferior to the traditional technique for the treatment of apical compartment in 12-month follow-up.

Catana, A. M., et al. (2023). "Strong relationships between the CA-125 KELIM score and the tumor biological effects after neo-adjuvant chemotherapy in advanced ovarian cancer patients: CHIVA trial (GINECO)." Annals of Oncology 34(Supplement 2): S532.
	Background: The modeled CA-125 longitudinal kinetic parameter KELIMTM during 1st-line chemotherapy is as a pragmatic indicator of the tumor primary chemosensivitiy. However, the links between KELIMTM and the beneath chemotherapy-induced tumor biological effects had to be explored. We studied the links between KELIMTM values and pathological response, and changes in TILs, in ovarian cancer patients treated with neo-adjuvant chemotherapy (NACT) +/- interval debulking surgery (IDS). Method(s): In the randomized phase II trial CHIVA (NCT01583322), 188 patients were treated with NACT carboplatin-paclitaxel +/- nintedanib, +/- IDS. Patient KELIMs were previously calculated. The pathological response was assessed with the Chemotherapy Response Score on the omentum (CRS 1-3), and with an enriched pathological response pR score based on the available tumor tissue block when omentum was lacking (pRS 1-3), obtained after NACT. Changes in stromal TILs (sTILs, % of the stromal surface on lymphocytes) and intra-epithelial TILs (ieTILs, qualitative appreciation, 0-2) in baseline tissue and after NACT were analyzed. Result(s): A strong association was found between patient KELIMTM value and the omentum CRS after NACT (n=67; median KELIMTM, 0.71 for CRS-1; 1.26 for CRS-2; 1.66 for CRS-3; P<0.01). Consistent, a correlation was observed between KELIM and tumor pRS (n=103; median KELIMTM, 0.73 for pRS-1; 1.25 for pRS-2; 1.61 for pRS-3; P <0.01). At baseline before NACT, no relationships between KELIMTM and TILs were found. After NACT, a significant association was observed between higher patient KELIMTM values and higher intra-epithelial TILs infiltrate after NACT (n=99; median KELIM, 0.88 for ieTILs score 0-1; vs 1.26 for ieTILs score 2; P = 0.03). Conclusion(s): High consistency was found between patients KELIMTM and the pathological response after neo-adjuvant chemotherapy, assessed with the omentum CRS score, or the larger tumor pRS score. Omentum may not necessarily needed to assess the pathological response. Intra-epithelial TILs change after NACT was strongly associated with KELIMTM-assessed chemosensitivity, thereby opening hypotheses about mechanisms of platinum-sensitivity. Clinical trial identification: NCT01583322. Legal entity responsible for the study: ARCAGY-GINECO (Paris, France). Funding(s): Hospital de la Timone (Marseille, France) and Universite Claude Bernard Lyon 1 (Lyon, France). Disclosure: G. Ferron: Financial Interests, Advisory Board: Olympus, AstraZeneca, MSD, Clovis Oncology, Rand-biotech; Financial Interests, Other, Honoraria: Olympus, AstraZeneca, MSD, Roche, Clovis Oncology, EISAI, GSK Tesaro, RanD Biotech; Financial Interests, Other, R&D contract: Olympus; Financial Interests, Other, Educational courses: Olympus, Rand-biotech; Financial Interests, Funding, Congress Funding: AstraZeneca, MSD, Roche, PharmaMar, EISAI, GSK Tesaro. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. P. Combe: Financial Interests, Advisory Board: AstraZeneca, BMS, MSD, EISAI, SANOFI, Novartis, Daiichi Sankyo, Clovis Oncology, GSK, Amgen; Financial Interests, Other, Investigator in clinical trial: MSD, Novartis, AstraZeneca, BMS. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, Ipsen, BMS, Bayer, Eisai; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Astellas; Financial Interests, Institutional, Coordinating PI: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Other, Travel: MSD, GSK. C. Lebreton: Financial Interests, Personal, Advisory B ard: GSK, MSD, Eisai, Clovis Oncology. J. Alexandre: Financial Interests, Personal, Advisory Board: Eisai, MSD, GSK, Janssen, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, MSD, AstraZeneca, GSK, Novartis; Financial Interests, Institutional, Research Grant: Janssen, GSK, MSD; Financial Interests, Institutional, Local PI: MSD, Eisai, Agenus, GSK, Immunogen, Incyte. P. Follana: Financial Interests, Personal, Invited Speaker: GSK, Eisai, MSD; Financial Interests, Personal, Advisory Board: Clovis, AZ, Novartis; Financial Interests, Personal, Other, Congress invitation: Gilead. B. You: Financial Interests, Personal, Advisory Board: AZ, MSD, Roche, GSK, Eisai, Seagen, Bayer, Novartis, Amgen, Clovis, BMS, Myriad, Menarini, Gilead. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Catarina, S. and M. Mariana (2023). "The effect of manual therapy on pain and fertility in women with endometriosis: a systematic review."
	
Cava, R. and Y. Orlin (2022). "Home-based transcutaneous tibial nerve stimulation for overactive bladder syndrome: a randomized, controlled study." International Urology and Nephrology 54(8): 1825-1835.
	Purpose: Transcutaneous posterior tibial nerve stimulation (TPTNS) for the treatment of overactive bladder syndrome (OAB), with or without urge urinary incontinence (UUI) using electrodes imbedded in the fabric of a conventional sock and an attachable battery-operated stimulation device (ZIDA-Exodus Innovations, Sufa, Israel), was compared for effectiveness and safety to a sham procedure in a prospective, blinded, randomized, controlled trial. Method(s): Forty patients with diagnosed with OAB were recruited from a single site. There were two groups: a treatment group (21 patients, mean age 64), which used an active ZIDA activation device (ZIDA) and a sham control group (SCG, 19 patients, mean age 72) randomized in a 1:1 ratio. After individual fitting of the sock and face-to-face instruction in the use of the device, patients in both groups self-administered the treatment once weekly for 30 min at home for a duration of 12 weeks. Prior to randomization and in Week 12, patients completed two 3-day bladder diaries and a quality-of-life (QOL) survey. Treatment success was defined as at least a 50% reduction in urgency voids with or without incontinence or at least a 30% reduction in 24-h frequency from baseline to Week 12. The key secondary endpoint was change in QOL from baseline to Week 12. Result(s): The success rate for the primary endpoint in the ZIDA group was 80% (n = 16/20) versus 39% (n = 7/18) in the SCG (p = 0.02). For QOL, the least squares mean difference in change from baseline to Week 12 between the ZIDA and sham control arms total score was - 12.7 (95% CI - 20.2 to - 5.1). No significant adverse effects were observed. Conclusion(s): TPTNS using the ZIDA home-based stimulation device offers a safe and effective treatment for patients with OAB syndrome and improves QOL. Trial regestration: TRN: NCT04470765.Copyright © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Cavalcante Marcelo, B., et al. (2023). "Peripheral blood natural killer cell cytotoxicity in recurrent miscarriage: a systematic review and meta-analysis." Journal of Reproductive Immunology 158: 103956.
	Dysregulated natural killer (NK) cells have been associated with recurrent miscarriages (RM). Studies have suggested that high peripheral blood NK cell cytotoxicities (pNKCs) are associated with an increased risk of RM. The aim of this systematic review (SR) and meta-analysis (MAs) is to investigate the difference in pNKC between nonpregnant and pregnant women with RM and controls and determine whether pNKC is reduced by immunotherapy. We searched the PubMed/Medline, Embase, and Web of Science databases. The MAs were conducted to compare pNKCs between women with and without RM before and during pregnancy as well as pre- and post-immunotherapy. Risk of bias in nonrandomized studies was assessed by the Newcastle-Ottawa Scale. Statistical analysis was performed using the Review Manager software. A total of 19 studies were included in the SR and 14 studies in the MAs. The MAs revealed higher pNKCs among nonpregnant women with RM compared to controls (MD, 7.99 95 %CI 6.40-9.58; p < 0.00001). pNKCs were also higher in pregnant women with RM than in pregnant controls (MD, 8.21 95 %CI 6.08-10.34; p < 0.00001). Women with RM showed significantly decreased pNKCs after the immunotherapy compared to before (MD, -8.20 95 %CI -10.20 - -6.19; p < 0, 00001). Additionally, there is an association between high pNKCs and the risk of pregnancy loss in women with RM. However, included studies showed substantial heterogeneities regarding the inclusion criteria of patients, techniques measuring pNKC, and types of immunotherapies. More studies are needed to evaluate the clinical efficiency of pNKCs in managing RM.; Competing Interests: Declaration of Competing Interest The authors have no relevant interests to declare. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cavalcante Marcelo, B., et al. (2021). "Lymphocyte immunotherapy in recurrent miscarriage and recurrent implantation failure." American journal of reproductive immunology (New York, N.Y. : 1989) 85(4): e13408.
	Problem: Lymphocyte immunotherapy (LIT) emerged in the early 1980s as a new therapeutic proposal for couples with a history of recurrent miscarriages (RM). However, in the early 2000s, the effectiveness of LIT was questioned. Recently, meta-analyses have observed the effectiveness and safety of LIT in treating couples with RM. Some studies evaluated the use of LIT in recurrent implantation failure (RIF) in in vitro fertilization cycles.; Methods: This systematic and narrative review evaluated the data available in the literature regarding the efficacy and safety of the use of LIT. Searches in PubMed/Medline, Embase, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "recurrent implantation failure".; Results: This review describes the historical aspects of LIT and discusses its protocols, mechanisms of action, side effects, complications, and current evidence of the effectiveness in cases of reproductive failure. It also discusses the use of LIT during the COVID-19 pandemic and new immunological therapies.; Conclusion: In the vast majority of studies, the use of LIT for RM couples has shown an improvement in pregnancy outcomes. The most of the current studies that support the evidence are quasi-experimental, with few randomized, double-blind studies (Level of evidence III). However, the current evidence are not convincing for the use of LIT in RIF patients. (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cavalcante Marcelo, B., et al. (2023). "Calcineurin inhibitors in the management of recurrent miscarriage and recurrent implantation failure: Systematic review and meta-analysis." Journal of Reproductive Immunology 160: 104157.
	Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications.; Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cavalcante, M. B., et al. (2020). "Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review." American Journal of Reproductive Immunology 83(6): e13242.
	Studies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: "recurrent implantation failure," "intrauterine infusion," "Platelet-Rich Plasma (PRP)," "Peripheral Blood Mononuclear Cells (PBMC)," "Granulocyte Colony-Stimulating Factor (G-CSF)," and "Human Chorionic Gonadotropin (hCG)." The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G-CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies.Copyright © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Cayir, G. and B. Kizilkaya (2022). "The effect of a counseling and training program on the treatment of women with overactive bladder." Psychology, health & medicine 27(8): 1726-1738.
	Anticholinergic drugs and behavioral interventions are effective methods for the treatment of OAB and UUI. This randomized controlled, prospective, and quasi-experimental study determined the effect of healthy lifestyle behavior training, based on the Health Promotion Model (HPM), on the treatment of women with Overactive Bladder (OAB). The study sample included intervention and control groups with a sample size of 100 women diagnosed with OAB who received pharmacological treatment and agreed to participate in the study. The data were collected using an Introductory Information Form, Urinary Diary, OAB Questionnaire (OAB-V8), King's Health Questionnaire (KHQ), Healthy Life Style Behavior Scale II (HLSB II), Brief Symptom Inventory (BSI), and 24-hour Pad Test. The intervention group was administered a 45-minute training program based on Pender's HPM. There was a statistically significantly higher level of decrease in urgency (z = -3,259;p = 0,001), nocturia (z = -3,691;p < 0,001), urge urinary incontinence (z = -2,391;p = 0,017), and urinary frequency (chi2 = 17,420;p < 0,001) in the intervention group during the posttest period. The study found a significant decrease in the total posttest scores of the women in the intervention group on the OAB-V8 (t = -6.955;p < 0.001), KHQ (t = -5.354;p < 0.001), and BSI (t = -6.463;p < 0.001) scales whereas a statistically significant increase was found in their total score on the HLSB II (t = 9.139;p < 0.001) scale. The study concluded that HLSB training, which was prepared based on HPM, reduced OAB symptoms among women, improved the quality of their lives, changed their HLSBs, and positively affected their psychological symptoms.

Ceccaroni, M., et al. (2021). "Dienogest vs GnRH agonists as postoperative therapy after laparoscopic eradication of deep infiltrating endometriosis with bowel and parametrial surgery: a randomized controlled trial." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(10): 930-933.
	BACKGROUND: The recurrence of deep infiltrating endometriosis (DIE) after its surgical excision is a big problem: postoperative treatment is crucial. OBJECTIVE: To compare two postoperative treatments: Dienogest and GnRH agonists. DESIGN: Prospective Randomized Controlled Trial (RCT). PATIENTS: 146 women submitted to laparoscopic eradication of DIE with bowel and parametrial surgery. INTERVENTIONS: Patients were randomized into two groups. Group A (n = 81) received Triptorelin or Leuprorelin 3.75 mg every 4 weeks for 6 months. Group B (n = 65) received Dienogest 2 mg/day for at least 6 months. A first interview made after six months valued compliance to therapy, treatment tolerability, pain improvement, and side effects. A second interview at 30 ± 6 months valued pain relapse, imaging relapse, and pregnancy rate. MAIN OUTCOMES: The primary outcome was to demonstrate the non-inferiority of Dienogest about the reduction in pain recurrence. Secondary outcomes were differences in terms of treatment tolerability, side effects, imaging relapse rate, and pregnancy rate. RESULTS: Both Dienogest and GnRH agonists were associated with a highly significant reduction of pain at 6 and 30 months, without any significant difference (p < .001). About treatment tolerability, a more satisfactory profile was reported with Dienogest (p = .026). No difference in terms of clinical relapse, imaging relapse, and live births was found. CONCLUSIONS: Dienogest has proven to be as effective as GnRH agonists in preventing recurrence of DIE and associated pelvic pain after surgery. Also, it is better tolerated by patients.

Cecere Sabrina, C., et al. (2023). "Safety of PARP inhibitors as maintenance therapy in ovarian cancer." Expert Opinion on Drug Safety 22(10): 897-908.
	Introduction: Antiangiogenic agents and poly(ADP-ribose) polymerase inhibitors (PARP-Is) have improved the outcome of patients suffering from ovarian cancer. However, as they are associated with many adverse events (AEs), it is important to be aware of their safety and toxicity profiles.; Areas Covered: We reviewed PARP-I therapeutical indications, mechanism of action, metabolism, and interactions. We reported on all major and minor AEs that have emerged from clinical trials (SOLO1, PRIMA, PAOLA1, ATHENA, SOLO2, NOVA, ARIEL3, NORA), their follow-ups, meta-analyses, and real-world studies, particularly hematologic toxicities and their management, and secondary malignancies (myelodysplastic syndrome and acute myeloid leukemia). We also addressed gastrointestinal, neurological, respiratory, hepatic, and renal toxicity and the use of PARP-Is in older, pregnant, and lactating patients. No specific research strategy in terms of keywords, inclusive dates and databases was used.; Expert Opinion: PARP-Is benefits largely outweigh the risks associated with potential AEs. Randomized controlled trials produced strong good, quality data, but they enrolled a selected population and failed to capture rare events. More pharmacovigilance data and real-life studies on a larger and more heterogeneous sample are needed to understand PARP-Is differences and to clarify the incidence of late AEs to balance the risk/benefit ratio.

Celik, O., et al. (2022). "Receptivity-based uterine fibroid surgery: an updated systematic review of the evidence." Clinical and Experimental Obstetrics and Gynecology 49(5): 114.
	Background: Analyzing expression patterns of receptivity genes is a minimally invasive diagnostic method to identify the underlying cause of subfertility in women with uterine fibroid with a history of implantation failure or recurrent pregnancy loss. This updated systematic review was designed to determine the molecular and genetic changes in the endometrium of women with fibroid and how myomctomy affect the outcome of spontaneous or assisted conception treatment. We also discussed the extent to which we should consider the effects of fibroids on endometrial receptivity when deciding whether or not to perform myomectomy. Method(s): A total of 184 articles reached as a result of PubMed research and meeting the selection criteria, were evaluated. Of these, 28 full text articles on uterine leiomyoma and endometrium, leiomyoma and receptivity, fibroid and implantation, myomectomy and implantation, fibroid and genes, fibroid surgery and receptivity, fibroid and uterine peristalsis, fibroid and immune cell were evaluated. Result(s): The endometrium of subfertile women with fibroid appears to have a disease specific pattern according to the type of the fibroid. The response of the endometrium to a fibroid may vary depending on whether the fibroid is close or far from it. Leiomyomas that contribute to subfertility must be near to or in contact with the endometrium, as is the case for Types 0, 1 and 2 leiomyomas. The proximity to the endometrial cavity makes the effect of fibroid on the endometrium more pronounced. While Type 3 fibroid causes subfertility similar to submucosal fibroids, the subfertility-producing effects of Type 4 fibroids have not been clearly clarified. However, the fact that the fibroid is far from the cavity should not mean that it has no effect on the endometrium. The mechanical stress created by a Type 4 fibroid that is not connected to the endometrium may be converted into biological signal and disrupt receptivity. Data on whether myomectomy restores impaired receptivity are mostly based on clinical observations, and studies evaluating endometrial receptivity before and after myomectomy are very few. Conclusion(s): Analysis of receptivity genes in subfertile women with fibroid may assist the clinician in deciding whether or not to perform myomectomy. If it is determined whether fibroids affect receptivity other than their mechanical effects, the indications for myomectomy may expand or narrow.Copyright © 2022 S.O.G. CANADA Inc.. All rights reserved.

Celiksoy, H. Y., et al. (2022). "Low Dose of Gonadotropin with Letrozole Versus High Dose of Gonadotropin in Patients with Poor Ovarian Response Undergoing Ivf: a Randomised, Single-Blind, Prospective Trial." Zeynep kamil tip bulteni 51(4): 221‐225.
	Objective: The ideal controlled ovarian stimulation protocol for patients with poor ovarian response (POR) is not clear yet, and is the subject of many studies. Aromatase inhibitors have been introduced as a new treatment modality in controlled ovarian stimulation as they were found to elevate follicular sensitivity to gonadotropins (Gn). The aim of this study was to evaluate whether it is possible to reduce the required Gn dose by adding letrozole to the treatment without compromising success. Material and Methods: Patients who underwent in vitro fertilization treatment between 2014 and 2015 in our department and who were classified as poor responder patients according to Bologna criteria were recruited and randomized. In the first group, 33 patients were treated with 150 IU Gn in combination with letrozole 5 mg /day for the first five days of the stimulation. In the second group, 27 patients were treated with 300 IU Gn. Results: Amoung the groups there were no statistically significant difference in duration of ovulation stimulation, duration of antagonist use, number of retrieved oocytes, number of transferred embryos, implantation, cycle cancelation, chemical, clinical and ongoing pregnancy rates (all p>0.05). Gn use was significantly higher in 300 IU Gn alone group compared to 150 IU Gn in combination with letrozole group (1354 ± 468 IU versus 2555 ± 725 IU, p<0.05). Conclusion: The addition of letrozole yields comparable pregnancy outcomes with significantly low doses of Gn, so may be regarded as an effective adjuvant agent in POR patients.

Cellier, M., et al. (2024). "Endometrial biopsy performed before the first in vitro fertilization does not impact the early pregnancy rate." Scientific Reports 14(1): 1153.
	Endometrial biopsy (EB) has been showed to increase the rate of clinical pregnancy in patients who underwent in vitro fertilization (IVF) failures. The purpose of this work was to assess the impact of an EB performed before the first in IVF on the early pregnancy rate. Be One study is a prospective, single-centre, randomized, open-label study. In this parallel study, patients were evenly split into two groups. In one group, patients underwent an EB between days 17 and 22 of the menstrual cycle that precedes the ovarian stimulation. In the other group (control), no EB was performed. The hCG-positive rate (early pregnancy rate) was evaluated on day 14 after the ovarian puncture. In total, 157 patients were randomized in the EB group and 154 patients were in the control group. The early pregnancy rate was 33.1% (52/157) in the EB group and 29.9% (46/154) in the control group (p=0.54). Other parameters, including perforation, endometritis, or pain level were reassuring. An EB performed during the luteal phase of the menstrual cycle preceding the stimulation of the first IVF did not increase early pregnancy rate.Copyright © 2024. The Author(s).

Cengiz, H., et al. (2021). "Vaginal-assisted Laparoscopic Sacrohysteropexy and Vaginal Hysterectomy with Vaginal Vault Suspension for Advanced Uterine Prolapse: 12-month Preliminary Results of a Randomized Controlled Study." Gynecology and Minimally Invasive Therapy 10(1): 30-36.
	OBJECTIVE: Vaginal-assisted laparoscopic sacrohysteropexy (VALH) is a new modified form of uterine-sparing prolapse surgery using a combined vaginal and laparoscopic approach. We aimed to compare 1 year efficacy and safety of VALH and vaginal hysterectomy with vaginal vault suspension (VH + VVS) in the surgical treatment of apical pelvic organ prolapse (POP). MATERIALS AND METHODS: Women who requested surgical treatment for stage 2-4 symptomatic uterine prolapse were recommended to participate in one year-long randomized study between July 2017 and January 2019. POP Quantification (POP-Q) examination and validated questionnaires such as International Consultation on Incontinence Questionnaire Vaginal Symptoms (IVIQ-VS) survey, Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire Short Form (IIQ-7), and Patient Global Impression of Improvement (PGI-I) were recorded at baseline and 12 months after surgery. The main primary outcome measure was apical prolapse recurrence. Secondary results were duration of surgery, pain score, blood loss, postoperative hospital stay, and quality of life scores related to prolapse. RESULTS: There were 15 women in VALH and 19 women in the VH + VVS group. ICIQ-VS score, ICIQ-QOL, UDI-6, and IIQ-7 scores were improved for both groups. According to the PGI-I scores, 80% of subjects in the VALH group, and 100% in the VH + VVS group, were "very much better" or "much better" with their prolapse symptoms at their 1-year follow-up. There was no reoperation or operation-related complication in both groups. CONCLUSION: VALH and VH + VVS have similar 1-year cure rates and patient satisfaction.

Center Asan, M. (2023). Patient Blood Mangement (PBM) Using IV Iron in Patients With Gynecologic Cancer.
	No Results Available Drug: Ferric Carboxymaltose 50Mg/Ml Inj 20Ml|Drug: RBC transfusion rate|hemoglobin differences|Frequency of anemia|Frequency and delay period of treatment|The costs that patients actually pay for treatment (Cost-effectiveness)|Quality of life of patients EORTC QLQ-C30|Adverse events|Quality of life of patients HINT-8 Female Not Applicable 334 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 2022-1674 December 2025

Center City of Hope, M. and C. Institute National (2023). Time-Restricted Eating Versus Nutritional Counseling for the Reduction of Radiation or Chemoradiation Tx Side Effects in Patients With Prostate, Cervical, or Rectal Cancers.
	No Results Available Procedure: Biospecimen Collection|Other: Informational Intervention|Other: Quality-of-Life Assessment|Other: Questionnaire Administration|Behavioral: Short-Term Fasting Cumulative double strand deoxyribonucleic acid (dsDNA) damage of normal tissue|Percentage of patients completing 4 weeks of time-restricted eating during RT|Rates of objective clinical adverse events (AEs)|Quality of life (QoL) indices - PR25|Quality of life (QoL) indices - CR29|Accumulated gH2ax foci|Oxidative DNA damage All Phase 2 60 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 21709|NCI-2023-00238|P30CA033572 January 1, 2027

Center Dubai, F. (2022). Immediate Ambulation Versus Short-time Bed Rest in Sub-fertile Women Undergoing Embryo Transfer.
	No Results Available Procedure: embryo transfer Percentage of participants who received or did not receive bed rest after embryo transfer who carried a viable pregnancy beyond 10 weeks' gestation|Percentage of participants who received or did not receive bed rest after embryo transfer who carried a viable pregnancy beyond 6 weeks' gestation|Percentage of participants who received or did not receive bed rest after embryo transfer who aborted before 12 weeks' gestation Female Not Applicable 156 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Other Bed rest after embryo transfer August 1, 2024

Center Erasmus, M. and W. Foundation (2024). Online Brief CBT Intervention for Women With PCOS.
	No Results Available Behavioral: online brief CBT intervention Depression|Anxiety|QoL|Coping Female Not Applicable 158 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: None (Open Label)|Primary Purpose: Treatment How2deal December 1, 2025

Center Fred Hutchinson, C. and N. Research National Institute of (2021). An AHEI Dietary Intervention to Reduce Pain in Women With Endometriosis.
	No Results Available Other: AHEI diet Pain Measurement|Quality of Life Questionnaire|Quality of Life Survey|Inflammatory Markers|Protein Measurement|Tumor Necrosis Factor Measurement|Tumor Necrosis Factor Measurement #2|inflammatory Markers Female Not Applicable 100 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment RG1004314|8772|R01NR017951 January 31, 2025

Center Leiden University, M., et al. (2024). Prednisolone Administration in Patients With Unexplained REcurrent MIscarriages.
	No Results Available Drug: Prednisolone|Drug: Placebo Live birth rate|Ongoing pregnancy|Congenital abnormalities|Gestational age|Survival at 28 days of neonatal life|Adverse events|Pregnancy complications|Direct and indirect costs|Anxiety and depression|Quality of life (Health state)|Birthweight|Productivity costs due to condition|Medical consumption Female Phase 2 490 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment LUMC-PREMI July 29, 2027

Center Leiden University, M., et al. (2021). Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features.
	No Results Available Drug: Olaparib|Radiation: Pelvic external beam radiotherapy|Drug: Chemotherapy|Drug: Durvalumab|Drug: Medroxyprogesterone Acetate|Drug: Megestrol Acetate|Radiation: Vaginal brachytherapy|Other: Observation p53abn-RED trial|MMRd-GREEN trial|NSMP-ORANGE trial|POLEmut-BLUE trial|Recurrence-free survival|Pelvic recurrence-free survival|Vaginal recurrence-free survival|Endometrial cancer-specific survival|Overall survival|Treatment-related toxicity - according to CTCAE v5.0|Health-related quality of life - Assessed using the EORTC QLQ-C30 questionnaire|Health-related quality of life - Assessed using the EORTC QLQ-EN24 questionnaire Female Phase 2|Phase 3 1615 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment RAINBO|ENGOT-en14-1,2,3,4|CCTG EN.10 TAPER arm A POLE January 1, 2031

Center, M. D. A. C. (2021). IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors.
	No Results Available Biological: Bevacizumab|Drug: Glutaminase-1 Inhibitor IACS-6274|Drug: Paclitaxel|Drug: Capivasertib Incidence of adverse events (AEs) All Phase 1 54 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2021-0265|NCI-2021-09063 May 29, 2026

Center Milton, S. H. M. (2024). Feasibility of a Mindfulness Intervention for Endometriosis Surgery.
	No Results Available Behavioral: pain education|Behavioral: mindfulness of pain introduction and intervention Use of opioid medication|Pain intensity|Sleep quality (sleep duration, awakenings, efficiency)|Sleep report|Emotional functioning|Patient global impression of change|Pain catastrophizing|Treatment satisfaction Female Not Applicable 20 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Health Services Research 23397 February 28, 2025

Center Ohio State University Comprehensive, C. (2022). Hyperthermic Intraperitoneal Chemotherapy With Cisplatin During Surgery or Cisplatin Before Surgery for the Treatment of Stage III or IV Ovarian, Fallopian Tube or Peritoneal Cancer.
	No Results Available Drug: Carboplatin|Drug: Cisplatin|Procedure: Cytoreductive Surgery|Drug: Hyperthermic Intraperitoneal Chemotherapy|Drug: Paclitaxel|Other: Quality-of-Life Assessment|Other: Questionnaire Administration Incidence of chemotherapy-related adverse events|Feasibility of chemotherapy immediately perioperatively|Percentage of patients in Arm C with a treatment free interval of < 8 weeks|Recurrence free survival|Tumor response|Quality of life (QOL) assessment EORTC QLQ-C30 All Early Phase 1 45 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment OSU-20277|NCI-2021-06207 December 31, 2024

Center Shaare Zedek, M. (2023). Acupuncture With/Without Self-acupressure for Post-oophorectomy Hot Flashes in BRCA Carriers.
	The present study will examine the effectiveness of acupuncture, with/without self-acupressure, on 200 post- RRSO patients who suffer from at least 5 hot flashes per day, including those treated with HRT. All participants will receive 8 weekly treatments with acupuncture, and then randomly assigned to receive (or not) self-administered acupressure, to be performed daily at home. The response to the study interventions will be assessed using daily Hot Flash Scores, the Menopause Specific Quality of Life (MenQoL) and Measure Yourself Concerns and Wellbeing (MYCAW) questionnaires (at baseline; at the end of the 8-week intervention; and at 16 weeks). The safety of the study treatments will be assessed throughout.

Center Texas, F. and O. Fertility (2022). Prospective, Randomized Trial Comparing ICSI to Insemination for Non-Male Factor Patients Undergoing PGT-A.
	No Results Available Procedure: ICSI Rate of karyotypically normal blastocysts|Rate of blastocyst development|Fertilization rate All Not Applicable 500 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment ICSI November 1, 2023

Center University Hospitals Cleveland, M., et al. (2021). Patient-Centered Outcomes in the Surgical Treatment of Uterovaginal Prolapse.
	No Results Available Procedure: Minimally invasive supracervical hysterectomy and sacrocolpopexy (MI-SCH+SCP)|Procedure: Vaginal hysterectomy with uterosacral ligament suspension (TVH+USLS) Treatment failure|Postoperative pain medication use|Change in surgical pain using VAS|Postoperative anti-emetic use|Change in nausea using VAS|Change in fatigue using MAF|Change in bladder function using UDI-6|Change in bladder function using IIQ-7|Change in bowel function using CRAD-8|Change in sexual function using PISQ-12|Change in sexual function using FSFI|Change in body image using BIPOP|Change in quality of life using P-QOL|Change in satisfaction with care using PGI-I|Rate of Grade I-V DINDO complications in each surgical arm Female Not Applicable 320 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 20210871 April 30, 2030

Center University of Texas Southwestern, M. and R. Institute Patient-Centered Outcomes (2024). IMPACT: Improving Maternal Postpartum Access to Care Through Telemedicine.
	The purpose of this study is to compare two complex, multi-component evidence-based postpartum interventions in underserved populations of lower socioeconomic status in an effort to reduce maternal morbidity and mortality. This large, multi-center randomized controlled trial will compare two multi-component postpartum care models via hybrid type 1 design conducted in two phases. An initial phase (phase 1) will collect baseline data and ensure patient input into final study. In phase 2, women will be randomized. Comparators are evidenced- based approaches: (1) an intensive in-person education with virtual education via push notifications using an electronic health record web portal; (2) a telehealth model using serial encounters. The "push" approach using notifications directly contrasts with the "pull" approach using telehealth visits. Both models include home visit programs. The study population includes patients delivering in two urban, inner-city health systems: Parkland (Dallas, TX) and Grady Memorial (Atlanta, GA). The primary outcome is time from hospital discharge to diagnosis and treatment of a composite of complications in the first 6 weeks. Based upon pilot data, 2349 women will demonstrate a 40% reduction (9 to 5.4 days) with 80% power and two-sided alpha of 0.05. 3500 women will be enrolled (1000 in phase 1; 2500 in phase 2) with anticipated <5% attrition at 6 weeks. Inclusion will be women who deliver liveborn infants. Secondary outcomes include mental health disorders, emergency room visits, hospital admissions, patient knowledge, quality of life and satisfaction, provider satisfaction, and social determinants of health. Women will be followed for one year postpartum.

Center Walter Reed National Military, M. (2021). BOTOX® at the Time of Prolapse Surgery for OAB.
	No Results Available Drug: OnabotulinumtoxinA 100 UNT|Other: Injectable saline Change from baseline to postoperative weeks 6 to 12 in Overactive Bladder bother short form (OAB-q SF) questionnaire looking for a decrease of 10 points, which is the minimally important difference.|Change from baseline to postoperative weeks 6 to 12 in the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12).|Change from baseline to postoperative weeks 6 to 12 in Patient Global Impression of Severity Scale (PGI-S).|Patient Global Impression of Improvement Scale (PGI-I) at 6 to 12 weeks postoperatively.|Urinary tract infection|Urinary retention Female Phase 4 138 U.S. Fed Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment 3-2021 June 2023

Center Walter Reed National Military, M. (2024). New Approaches to Nerve Stimulation Therapy for Bladder Pain Syndrome.
	No Results Available Procedure: Pulsed radiofrequency ablation|Procedure: Sham ablation VAS Pain Score|O' Leary-Sant Voiding and Pain Indices|Average number of daytime voids over the prior week|Average number of daytime episodes of urinary incontinence over the prior week|Patient Health Questionnaire - 9 (PHQ-9)|Number of treatments currently taking for BPS|Patient Global Impression of Severity (PGI-S)|Patient Global Impression of Improvement (PGI-I) Female Not Applicable 38 U.S. Fed Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment WRNMMC-2023-0433 May 2026

Center Wolfson, M. (2022). Biweekly Follow-Up and At-Home Ultrasound Reduce Anxiety in Women With Recurrent Pregnancy Loss.
	No Results Available Device: PulseNmore ES™|Device: Standard Ultrasound Anxiety levels Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care WOMC-0130-22 April 1, 2025

Central, T. and O. Group Eastern European Gynecologic (2022). Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy.
	No Results Available Radiation: No adjuvant therapy|Radiation: Adjuvant radiotherapy Disease-free survival|Overall survival|Pelvic disease-free survival|Health-related quality of life based questionnaire|Treatment-related adverse events based on Common Terminology Criteria for Adverse Events v5.0 Female Phase 3 514 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ENGOT-cx16/CEEGOG/CERVANTES December 2032

Centre Universiti Kebangsaan Malaysia, M. (2021). Vaginal Hygiene Wash as Adjunct Treatment in Bacterial Vaginosis.
	No Results Available Other: Vaginal hygiene wash|Other: placebo wash Bacterial vaginosis cure rate|Visual analog scale of symptoms before treatment|Visual analog scale of symptoms after treatment|Microbial profile of vaginal flora before treatment|Microbial profile of vaginal flora after treatment|Cytokines concentration before treatment|Cytokines concentration after treatment|Recurrence of symptoms 1 month after completed treatment|Microbial analysis of vaginal flora 1 month after completed treatment Female Not Applicable 56 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment FF-2021-031 January 2022

Ceriani, C. E. J. and S. D. Silberstein (2023). "Current and emerging pharmacotherapy for menstrual migraine: a narrative review." Expert Opinion on Pharmacotherapy 24(5): 617-627.
	Introduction: In this article, we discuss menstrual migraine (MM), which can be categorized as menstrually related migraine (MRM) or pure menstrual migraine (PMM). MM attacks are often longer, more severe, and harder to treat than other migraine attacks. Appropriate treatment strategies include acute treatment, short term preventive treatment, and daily preventive treatment, depending on the patient's pattern of migraine and occurrence of migraine outside the menstrual period. Areas covered: A PubMed, Cochrane Library, Medline, and Ovid search from inception to October 2022 provided articles relating to MM pathophysiology and treatment. Expert opinion: In patients for whom standard acute therapy is inadequate, short term or daily preventive treatment should be considered. Patients with PMM may be adequately managed with short term preventive treatment started 2 days prior to the onset of migraine and continued for 5-6 days. Frovatriptan is the mainstay of short-term prevention. Patients who experience additional attacks outside the menstrual period may benefit from daily preventive treatment. Estrogen-containing contraceptive treatment may be effective in appropriately selected patients. Emerging research on the pathophysiology of MM indicates that oxytocin agonists and CGRP antagonists may prove to be effective treatment options.Copyright © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Čerina, D., et al. (2022). "Is There a Place for Adjuvant Chemotherapy in the Treatment of Locally Advanced Cervical Cancer?" Current oncology (Toronto, Ont.) 29(8): 5223-5237.
	Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.

Cerrahpasa Istanbul, U. (2022). The Effect of Digital Literacy Education Given to Postmenopausal Women on Health Literacy and Quality of Life.
	No Results Available Behavioral: digital literacy education specific to menopause digital literacy education increases the digital literacy level of women|digital literacy education increases women's health literacy level|digital literacy education improves women's menopause-specific quality of life Female Not Applicable 100 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Supportive Care E-74555795-050.01.04-519850 March 2023

Cerrahpasa Istanbul, U. (2023). The Effect of Baby Massage Training Given to Pregnant Women on Maternal Attachment and Postpartum Depression.
	No Results Available Behavioral: Baby massage the Maternal Attachment Scale (mother-baby bonding scale)|The Edinburgh Postpartum Depression Scale Female Not Applicable 54 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Prevention 2023/132 July 30, 2024

Cerrahpasa Istanbul, U. and M. University Ondokuz (2023). Kegel and Abdominal Exercises on Urinary Incontinence Severity, Quality of Life, and Sleep Quality in Menopausal Women.
	No Results Available Behavioral: Experimental Group: Kegel exercises and abdominal exercises|Behavioral: Control Group: Kegel exercises Urinary Incontinence Severity|Quality of life of women with urinary incontinence will be evaluated|Sleep Quality Female Not Applicable 70 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Supportive Care B.30.2.ODM.0.20/60-164 November 20, 2023

Certelli, C., et al. (2020). "Electrochemotherapy in vulvar cancer: A systematic review." Italian Journal of Gynaecology and Obstetrics 32(1): 34-43.
	There are some problems about the optimal treatment modality of vulvar cancer (VC): unfeasible surgery in elderly women with several comorbidities and the absence of treatments applicable in recurrent disease. For these reasons, Electrochemotherapy (ECT) may have an important role in the management of these patients. The aim of this systematic review is to evaluate ECT in VC in terms of clinical response, adverse events and quality of life (QoL). We conducted a search on the electronic database PubMed/MED-LINE. All the studies in English language published from 2006 and August 2019 were considered eligible. The 4 studies included in the systematic review reported an overall objective response rate (complete and partial response) was 74.3%. No treatment-related serious adverse events were reported in any of the studies. An improvement in the QoL was reported. In conclusion, ECT is an easy, quick to perform, less invasive and repeatable procedure, which have shown a positive clinical response, a reduction in symptoms and an improvement in QoL. Since the survival for advanced and metastatic diseases has been, fortunately, increased, it is also important to focus our efforts on the QoL and on the local control of the disease.Copyright © 2020 Global Research Online. All rights reserved.

Cetin, B. and O. Gumusay (2023). "PD-1 and PD-L1 Blockade plus Chemotherapy in Endometrial Cancer." The New England Journal of Medicine 389(9): 866-867.
	
Ceyhan, T., et al. (2023). "Repeated application of luteal phase oestradiol/GnRH antagonist priming increases IVF success for poor ovarian reserve patients." Journal of Obstetrics and Gynaecology 43(2): 2211664.
	We aimed to compare repeated LPP (luteal phase oestradiol LPP/GnRH antagonists protocol) treatment with different protocol results with poor ovarian response (POR) patients. Two hundred and ninety-three cycles with poor ovarian reserve who underwent LPP, microdose flare up protocol and antagonist protocol were included in the study. Of these, 38 patients were applied LPP in the first cycle and LPP in the second cycle. After the microdose or antagonist protocol applied in the first cycle, LPP was applied to 29 patients in the second cycle. There are 128 patients who received LPP only once and 31 patients who received microdose flare up only once. The clinical pregnancy rate was monitored higher in LPP application group in the second cycle than the patients who received only LPP and patients who received LPP after different protocols (p = .035). b-hCG positivity per embryo and clinical pregnancy rate were found to be significantly higher with the LPP application in the second protocol (p = .000, p = .001). Repeated LPP may be the first choice protocol for low ovarian reserve patients.Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Cezar, C., et al. (2021). "Can uterine artery embolization be an alternative to plastic and reconstructive uterus operation by minimally invasive surgery?" GMS Interdisciplinary plastic and reconstructive surgery DGPW 10: Doc07.
	Introduction: Plastic and reconstructive minimally invasive surgery has been established as gold standard in myomectomy. Therapy failure eventually leads to future surgical interventions or hysterectomy: surgeons and patients should be aware of the risks and benefits. We conducted a systematic review to analyse the evidence on the therapeutic indications and adverse events associated with uterine artery embolization and thereby evaluating if this method could be a valid alternative therapy. Methods: In concordance with PRISMA guidelines, literature research was made in PubMed, Cochrane Library, UpToDate, Amboss and Medline databases. Clinical trials, reviews and case reports published in English between January 2010 and June 2020 were included. Results: 44 articles were included out of 838 papers identified at initial search. Regarding uterine fibroids, three original papers and one Cochrane review reported the benefits of the procedure as an alternative to surgery, even in large and giant fibroids. Furthermore, several studies discussed the use of embolization for postpartum haemorrhage to decrease rates of hysterectomy after other haemostatic methods were exhausted, because of the potential risk of abnormal placentation in a future pregnancy. The procedure can also be successfully used as prophylactic method in different obstetrical procedures. Conclusions: The use of embolization in different uterine pathologies is a minimally invasive procedure as an alternative to surgery, especially in women who desire to preserve their uterus. Its related complications are described and can be avoided by a stringent indication of the procedure. More evidence regarding fertility after UAE, use of the procedure prophylactically in obstetrical haemorrhage or in adenomyosis is needed.; Competing Interests: The authors declare that they have no competing interests. (Copyright © 2021 Cezar et al.)

Cha, D. S., et al. (2024). "The efficacy of zuranolone in postpartum depression and major depressive disorder: a review & number needed to treat (NNT) analysis." Expert Opinion on Pharmacotherapy 25(1): 5-14.
	Introduction: Major depressive disorder (MDD) is a common and debilitating mental illness. Postpartum depression (PPD) impacts women globally and is one of the most common complications of childbirth that is underdiagnosed and undertreated, adversely impacting the mental health of women, children, and partners. Available antidepressant medications require weeks to months before showing effect. In this setting, zuranolone, an oral neuroactive steroid and a positive allosteric modulator of GABAA receptors, is an attractive alternative as a rapid-acting antidepressant treatment. Areas covered: This article reviews zuranolone (SAGE217), focusing on available clinical studies in individuals with PPD and MDD. This paper adds to the extant literature by presenting the efficacy data as Number Needed to Treat (NNT) to facilitate indirect comparisons with other antidepressants. Expert opinion: Zuranolone is a novel rapid-acting (i.e. two week course) oral antidepressant for the treatment of adults with PPD with ongoing clinical trials evaluating its efficacy in adults with MDD. Zuranolone is well tolerated with no significant safety concerns in any clinical trials completed to date. Zuranolone will be scheduled by the Drug Enforcement Agency (DEA).Copyright © 2024 Informa UK Limited, trading as Taylor & Francis Group.

Chae Su, H., et al. (2019). "Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis." Gynecologic Oncology 154(3): 638-650.
	Objectives: To assess the effect of adjuvant chemotherapy (AC) or radiotherapy (AR) on the risk of recurrence in surgically treated patients with early-stage uterine leiomyosarcoma (uLMS).; Methods: We searched the PubMed, EMBASE, and MEDLINE, and Cochrane databases for publications up to March 2019, which compared patients with early-stage uLMS who received AC or AR with those who did not. The primary endpoint was recurrence rate. Random- or fixed-effects models were used for pooled estimates of the effect of adjuvant treatments on recurrence rates. Subgroup analyses were conducted based on study design, surgical staging, AC regimen (gemcitabine/docetaxel regimen), and type of AR.; Results: Three randomized trials and 9 observational studies (9 studies for AC vs. observation, n = 496; 9 studies for AR vs. observation, n = 425) were included. The meta-analysis indicated that AC did not decrease the risk of recurrence compared with observation (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.37-1.15, P = 0.14; P = 0.09 and I 2 = 42.1). Similarly, AR did not decrease the risk of recurrence compared with observation (OR = 1.11, 95% CI = 0.56-2.21, P = 0.76; P = 0.10 and I 2 = 40.4). Meta-regression analyses revealed no significant association between median follow-up time and recurrence. In subgroup analyses (study design, surgical staging, gemcitabine/docetaxel regimen, type of AR), neither AC nor AR decreased the risk of recurrence significantly.; Conclusion: AC, including gemcitabine/docetaxel regimen, or AR did not reduce the recurrence rate in patients with early-stage uLMS. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chae-Kim, J., et al. (2021). "Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(12): 1499-1505.
	Objective: Progestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.; Methods: A systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.; Results: In total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).; Conclusion: For reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.; Prospero Registration Number: CRD42020179069.disease remission.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Chaemsaithong, P., et al. (2020). "Does low-dose aspirin initiated before 11 weeks' gestation reduce the rate of preeclampsia?" American Journal of Obstetrics and Gynecology 222(5): 437-450.
	Objective Data: Preconception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization, and organogenesis. Most studies have evaluated the potential benefit of preconception or early administration of low-dose aspirin in women with a history of recurrent pregnancy loss, women who have undergone in vitro fertilization, or women with thrombophilia or antiphospholipid syndrome. These women are at an increased risk of placenta-associated complications of pregnancy, including preeclampsia, preterm delivery, and fetal growth restriction.; Study Outcomes: We performed a systematic review and meta-analysis to evaluate the effect of low-dose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction.; Study Appraisal and Synthesis Methods: We searched in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from 1985 to November 2018. Entry criteria were randomized controlled trials evaluating the effect of aspirin administered at <11 weeks' gestation in preventing preeclampsia and/or hypertensive disorders in pregnancy or improving pregnancy outcomes in women with recurrent miscarriage as compared with placebo or no treatment and outcome data available or provided by authors for >85% of the study population. Relative risks with 95% confidence intervals were calculated for each study and pooled for global analysis as the effect measure. We assessed statistical heterogeneity in each meta-analysis using the χ 2 statistics, I 2 , and Tau 2 . Heterogeneity was considered substantial if an I 2 was greater than 50% and either the Tau 2 was greater than zero or there was a low P value (<0.10) in the χ 2 test for heterogeneity. Random-effects meta-analysis, weighted by the size of the studies, was performed to produce an overall summary on aspirin effect for each outcome. Sensitivity analysis by sequential omission of each individual study and by fixed-effects model was performed. Publication bias was not assessed because of the small number of included studies. Statistical analysis was performed using Stata release 14.0 (StataCorp).; Results: The entry criteria were fulfilled by 8 randomized controlled trials on a combined total of 1426 participants. Low-dose aspirin initiated at <11 weeks' gestation was associated with a nonsignificant reduction in the risk of preeclampsia (relative risk, 0.52; 95% confidence interval, 0.23-1.17, P = .115), gestational hypertension (relative risk, 0.49; 95% confidence interval, 0.20-1.21; P = .121), and any hypertensive disorder of pregnancy (relative risk, 0.59; 95% confidence interval, 0.33-1.04, P = .067). Early administration of low-dose aspirin reduced the risk of preterm delivery (relative risk, 0.52; 95% confidence interval, 0.27-0.97, P = .040) but had no impact on the risk of fetal growth restriction (relative risk, 1.10; 95% confidence interval, 0.58-2.07, P = .775). Except for preterm delivery and any hypertensive disorder of pregnancy, sensitivity analysis demonstrated similar observations, therefore confirming the robustness of the analysis.; Conclusion: The administration of low-dose aspirin at <11 weeks' gestation in women at high risk does not decrease the risk of preeclampsia, gestational hypertension, any hypertensive disorder of pregnancy, and fetal growth restriction. However, it might reduce the risk of preterm delivery. Larger randomized controlled trials will be required to substantiate the findings. (Copyright © 2019. Published by Elsevier Inc.)

Chaisson, N. and M. Schafer Katherine (2023). "Streamlining the Use of Mifepristone for Early Pregnancy Loss Across a Large Health Care System Sets the Stage for Rapid Expansion of Medication Abortion Access in a Post-Roe Environment." Annals of Family Medicine 21(5): 469.
	
Chakraborty, P., et al. (2022). "Significance of Hyperhomocysteinemia in Immediate As Well As Long-Term Health Risk/s in Women with Polycystic Ovary Syndrome: a Probabilistic Model Using Dynamic Bayesian Network Analysis." Reproductive sciences (Thousand Oaks, Calif.).
	Polycystic ovary syndrome (PCOS) is a heterogeneous entity comprising broad spectra of ovarian disorders with trademark features of metabolic syndrome like insulin resistance, obesity, and dyslipidaemia to name a few. Hyperhomocysteinemia, an independent risk factor of metabolic syndrome, has been suggested as a causative factor in spontaneous miscarriage in PCOS. However, it is yet to be resolved whether hyperhomocysteinemia has a contributory role in the pathogenesis or could direct long-term sequences of the syndrome. A total of 2355 women with history of one or more first trimester abortions were screened and 1539 were selected for the study. Selected patients were initially divided by the presence or absence of PCOS, while subsequent stratification was based on hyperhomocysteinemia, insulin resistance, and/or obesity. The miscarriage population/s was mostly represented by hyperhomocysteinemia in both the cohorts (PCOS: 69.08% vs. non-PCOS: 56.68%). ROC-AUC values suggest increased predisposition of hyperhomocysteinemia-mediated miscarriage (hyperhomocysteinemia: 0.778; insulin resistance: 0.601; BMI: 0.548). A probabilistic causal model was designed using dynamic Bayesian network to evaluate the time-series data points before, during, and after pregnancy which revealed a possibility of 32.24% (n = 79) of PCOS cohort developing hypertension, 26.94% (n = 66) of onset of diabetes and 4.49% cardiovascular disease 3 years following pregnancy. We conclude hyperhomocysteinemia may possibly contribute to spontaneous miscarriage and related to metabolic derailments later in life.

Chalkidou, A., et al. (2023). "The Comparative Study of the Administration of the Combination Preparation of Isoflavones and Hyaluronic Acid in Menopausal Women for the Treatment of the Symptoms of Menopause, Urogenital Atrophy and Oteoporosis in Relation to Existing Hormone Replacement Therapies." Materia socio-medica 35(3): 206-214.
	Background: Menopause is characterized by a series of symptoms and effects from the various systems and organs, for which, the decline in estrogen production from the ovaries is considered responsible.; Objective: The aim of this study was to make comparative study of the administration of the combination preparation of isoflavones and hyaluronic acid in menopausal women for the treatment of the symptoms of menopause, urogenital atrophy and osteoporosis in relation to existing hormone replacement therapies.; Methods: In this five-year, double-blind, placebo-controlled clinical study, a total of 274 postmenopausal women were enrolled and classified into three groups. Participants in group A, were 96 women who did not receive Hormone Replacement Therapy (HRT), in the second group, 92 received daily treatment with tibolone (2.5 mg) as monotherapy, and in the third group, 86 received treatment with a pharmaceutical formulation of hyaluronic acid 120 mg and isoflavones. MF11RCE 80 mg.; Results: In the postmenopausal women of our study, a significant reduction of postmenopausal symptoms was found in both groups B and C of participants who received hormone replacement preparations compared to group A who did not receive HRT. Furthermore, no difference in efficacy was observed between the administered preparations of isoflavones and tibolone.; Conclusion: The combination of isoflavones and hyaluronic acid has the same efficacy as tibolone in menopausal symptoms.; Competing Interests: There are no conflicts of interest. (© 2023 Anna Chalkidou, Efthimios Oikonomou,, Dimitrios Lambrinos, Anastasia Bothou, Dimitrios Kyriakou, Konstantinos Nikolettos, Georgios Marinos. Georgios Iatrakis, Stefanos Zervoudis, Nikolaos Nikolettos. Panagiotis Tsikouras.)

Chambers, L. M., et al. (2021). "Impact of treatment modality on overall survival in women with advanced endometrial cancer: A National Cancer Database analysis." Gynecologic Oncology 160(2): 405-412.
	OBJECTIVE: To evaluate overall survival (OS) in women with advanced endometrial cancer (EC) following chemotherapy alone (CT), neoadjuvant chemotherapy and interval debulking surgery (NACT + IDS) or primary cytoreductive surgery and chemotherapy (PCS + CT). METHODS: The National Cancer Database (NCDB) was queried for patients with stage III/IV EC from 2004 to 2015. Univariable and multivariable Cox proportional hazards analyses assessed the impact of treatment modality upon OS. RESULTS: Of 48,179 women identified, 5531 received CT (11.5%), 2614 NACT + IDS (5.4%) and 40,034 PCS + CT (83.1%). Median OS was 11.1 months for CT, 25.1 months for NACT + IDS and 60.9 months for PCS + CT (p < 0.001). On multivariate analysis, NACT + IDS (HR 0.44 (0.40, 0.49); p < 0.001) and PCS + CT (HR 0.32 (0.30, 0.35); p < 0.001) were associated with improved OS vs. CT alone. Age, African American race, income, higher Charlson comorbidity index and grade were predictors of worse OS (p < 0.001). On subgroup analysis by stage (III/IV) and histology (Type I/II), PCS + CT improved OS for all patients, compared to NACT + IDS (p < 0.001) and CT (p < 0.001). NACT + IDS was associated with improved OS vs. CT in stage III type I (HR 0.50; 95% CI 0.38, 0.67; p < 0.001), stage IV type I (HR 0.43; 95% CI 0.35, 0.52; p < 0.001), and stage IV type II EC (HR 0.43; 95% CI 0.36, 0.51; p < 0.001), but not stage III type II EC (HR 0.76; 95% CI 0.56, 1.03; p = 0.08). CONCLUSIONS: In women with advanced EC, PCS + CT is associated with improved OS compared to NACT + IDS or CT alone, regardless of stage or histology. Additionally, NACT + IDS is associated with superior OS in stage III type I and all stage IV EC compared to CT alone. Where feasible, surgery should be incorporated into treatment planning in women with advanced EC.

Chan Michelle, C., et al. (2022). "Rhesus isoimmunisation in unsensitised RhD-negative individuals seeking abortion at less than 12 weeks' gestation: a systematic review." BMJ Sexual & Reproductive Health 48(3): 163-168.
	Aim: The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an abortion. This review is registered with Prospero.; Methods: A search for all published and ongoing studies, without restrictions on language or publication status, was performed using the following databases from their inception: EBM Reviews Ovid - Cochrane Central Register of Controlled Trials, MEDLINE Ovid (Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily), Embase.com, Popline and Google Scholar. Study types included: randomised controlled trials, controlled trials, cohort and case-control studies from 1971 onwards. The population included women who undergo an abortion (induced, incomplete, spontaneous or septic abortion), medical or surgical <12 weeks, and isoimmunisation in a subsequent pregnancy. The primary outcomes were: (1) development of a positive Kleihauer-Betke test and (2) development of Rh alloimmunisation in a subsequent pregnancy.; Results: A total of 2652 studies were screened with 105 accessed for full-text review. Two studies have been included with high bias appreciated. Both studies found few women to be sensitised in forming antibodies after an abortion. The limited studies available and heterogeneity prevent the conduction of a meta-analysis.; Conclusions: Rh immunoglobulin has well-documented safety. However, it is not without risks and costs, is a possible barrier to delivering efficient services, and may have limited availability in some countries. The evidence base and quality of studies are currently limited. There is unclear benefit from the recommendation for Rh testing and immunoglobulin administration in early pregnancy. More research is needed as clinical practice guidelines are varied, based on expert opinions and moving away from testing and administration at time of abortion.; Implications: There is limited evidence surrounding medical benefit of Rh testing and immunoglobulin administration in early pregnancy. Further research is needed to define alloimmunisation and immunoglobulin benefit to update standards of care. Additionally, other factors should be considered in forming clinical policies and guidelines such as costs, feasibility and impact on access to care for patients.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chan, S. Y., et al. (2023). "Time-to-conception and clinical pregnancy rate with a myo-inositol, probiotics, and micronutrient supplement: secondary outcomes of the NiPPeR randomized trial." Fertility and Sterility 119(6): 1031-1042.
	Objective: To determine whether a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rates. Design(s): Secondary outcomes of a double-blind randomized controlled trial. Setting(s): Community recruitment. Patient(s): Women aged 18 to 38 years planning to conceive in the United Kingdom, Singapore, and New Zealand, excluding those with diabetes mellitus or receiving fertility treatment. Intervention(s): A standard (control) supplement (folic acid, iron, calcium, iodine, beta-carotene), compared with an intervention additionally containing myo-inositol, probiotics, and other micronutrients (vitamins B2, B6, B12, D, zinc). Main Outcome Measure(s): Number of days between randomization and estimated date of natural conception of a clinical pregnancy, as well as cumulative pregnancy rates at 3, 6, and 12 months. Result(s): Of 1729 women randomized, 1437 (83%; intervention, n=736; control, n=701) provided data. Kaplan-Meier curves of conception were similar between intervention and control groups; the time at which 20% achieved natural conception was 90.5 days (95% confidence interval: 80.7, 103.5) in the intervention group compared with 92.0 days (76.0, 105.1) in the control group. Cox's proportional hazard ratios (HRs) comparing intervention against control for cumulative achievement of pregnancy (adjusted for site, ethnicity, age, body mass index, and gravidity) were similar at 3, 6, and 12 months. Among both study groups combined, overall time-to-conception lengthened with higher preconception body mass index, and was longer in non-White than in White women. Among women who were overweight the intervention shortened time-to-conception compared with control regardless of ethnicity (12-month HR=1.47 [1.07, 2.02], P=.016; 20% conceived by 84.5 vs. 117.0 days) and improved it to that comparable to nonoverweight/nonobese women (20% conceived by 82.1 days). In contrast, among women with obesity, time-to-conception was lengthened with intervention compared with control (12-month HR=0.69 [0.47, 1.00]; P=.053; 20% conceived by 132.7 vs. 108.5 days); an effect predominantly observed in non-White women with obesity. Conclusion(s): Time-to-natural-conception and clinical pregnancy rates within a year were overall similar in women receiving the intervention supplement compared with control. Overweight women had a longer time-to-conception but there was suggestion that the supplement may shorten their time-to-conception to that comparable to the nonoverweight/nonobese women. Further studies are required to confirm this. Clinical Trial Registration Number: clinicaltrials.gov (NCT02509988)Copyright © 2023 The Authors

Chancellor, M. B., et al. (2021). "An evaluation of women with persistent or recurrent stress urinary incontinence (SUI) following surgery in a double-blind, randomized, controlled trial comparing safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) with placebo (PBO)." Journal of urology 206(SUPPL 3): e99‐e100.
	INTRODUCTION AND OBJECTIVE: Women with persistent or recurrent SUI following prior surgical intervention have an unmet medical need with symptoms which substantially impact daily functioning and quality of life (QOL). METHODS: Data provided are a stratified subset from a Phase 3 study (NCT01893138). 75 women with average 19.8±11.3 stress leaks over 3 days were randomized 2:1 (150 x 106 AMDC‐USR:vehicle PBO) at 22 sites. AMDC‐USR was manufactured from skeletal muscle tissue harvested from the vastus lateralis via outpatient biopsy and injected into the urinary sphincter during a subsequent outpatient procedure. SUI was monitored by 3‐day diaries of stress incontinence episode frequency (SIEF) and QOL questionnaires during blinded follow‐up through 12 months. RESULTS: All women completed 12‐month visits (50 AMDCUSR; 25 PBO). Treatment effect at ≥75% SIEF reduction was robust and significant. SIEF reduction in AMDC‐USR correlated with improvement in all QOL scores at 12 months (p 0.002) and exceeded clinically meaningful levels of ≥ 10‐point improvement in I‐QOL score at ≥75% reduction in SIEF. There were significant differences in QOL changes between responders and non‐responders in the AMDC‐USR group only. There were no AMDC‐USR‐related serious adverse reactions. CONCLUSIONS: Women with chronic SUI symptoms (average > 12 years) sought treatment despite undergoing as many as five prior surgeries at the time of enrollment. A single injection of AMDCUSR may be a safe and effective treatment in this challenging refractory population. Based in part on this evidence to address unmet medical need and the recognized seriousness of the condition, AMDC‐USR has been granted the expedited Regenerative Medicine Advanced Therapy (RMAT) designation by the United States Food and Drug Administration for this population.

Chang, C., et al. (2021). "The Impact of Bariatric Surgery Compared to Metformin Therapy on Pregnancy Outcomes in Patients with Polycystic Ovarian Syndrome: a Systematic Review and Meta-analysis." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 25(2): 378-386.
	Background: Polycystic ovarian syndrome (PCOS) is a leading cause of infertility among women of reproductive age. The interplay between hyperinsulinemia and obesity results in many of the reproductive and hormonal changes seen in PCOS including abnormal menses, infertility, and pregnancy loss. While bariatric surgery has been found to be an effective treatment strategy for morbid obesity, its role in the management of PCOS-related infertility compared to standard therapy (metformin) is less clear.; Aims: To assess the impact of bariatric surgery on pregnancy outcomes in women with PCOS compared to metformin therapy in a systematic review and meta-analysis.; Methods: MEDLINE, EMBASE, PubMed, and Google Scholar were searched from inception to August 2019. Studies that reported quantitative data on pregnancy outcomes on women of reproductive age with PCOS with at least a 3-month follow-up and a minimum of 5 or more sample size were included. The primary outcome was pregnancy rate, expressed as an event rate and 95% confidence interval (95% CI).; Results: Ten studies with a total of 587 patients were included in the final analyses (Metformin: 5 studies, n = 192; Bariatric surgery (BS): 5 studies (2 Roux-en-Y gastric bypass, 2 sleeve gastrectomy, 1 Roux-en-Y gastric bypass + sleeve gastrectomy), n = 186). The average time to follow-up was 18.25 months (range 3-36) with a shorter time to follow-up in the metformin group compared to the bariatric surgery group (Metformin: 11.2 vs BS: 24.5 months). While metformin increased the likelihood of pregnancy compared to placebo or non-surgical interventions (OR = 3.08, 95% CI 1.29-7.37, p = 0.01), the pregnancy rate after bariatric surgery was greater than metformin (34.9%, 95% CI 0.20-0.53 vs 17.1%, 95% CI 0.12-0.23, p = 0.026 for the difference). Additionally, there was a trend to a greater improvement in menstrual irregularity in the bariatric group compared to the metformin group with a reduction of 92% in the bariatric cohort compared to a reduction of 54% in the metformin cohort, but the data was limited.; Conclusion: Bariatric surgery appears to be a more effective treatment strategy for patients with PCOS and class 3 obesity compared to metformin alone. Women with PCOS and infertility should consider bariatric surgery for weight loss and improvement in pregnancy outcomes.

Chang, C.-L., et al. (2022). "Comparing the outcomes and effectiveness of robotic-assisted sacrocolpopexy and laparoscopic sacrocolpopexy in the treatment of pelvic organ prolapse." International Urogynecology Journal 33(2): 297-308.
	Introduction and Hypothesis: Abdominal sacrocolpopexy is regarded as the gold standard for management of pelvic organ prolapse (POP). Nowadays, minimally invasive surgeries are preferred, and sacrocolpopexy can be performed using either a laparoscopic or robotic-assisted approach. The aim of the current study was to compare the efficacy and safety of robotic-assisted sacrocolpopexy (RASC) and laparoscopic sacrocolpopexy (LSC) through an updated systematic review and meta-analysis.; Methods: We performed a systematic literature review of different databases and related references from their inception until July 2020 without language restrictions. All randomized control trials and comparative studies that compared RASC and LSC for the management of POP were included.; Results: A total of 13 studies including 2115 participants were included for the pooled analysis. The pooled results revealed that RASC was associated with a significantly longer operative time (weighted mean difference, 29.53 min; 95% confidence interval [CI], 12.88 to 46.18 min, P = 0.0005), significantly less estimated blood loss (weighted mean difference, -86.52 ml; 95% CI -130.26 to -42.79 ml, P = 0.0001), significantly fewer overall intraoperative complications (odds ratio [OR] 0.6; 95% CI 0.40 to 0.91; P = 0.01) and significantly lower conversion rate (OR 0.39; 95% CI 0.19 to 0.82; P = 0.01) compared with LSC. There were no significant differences between the length of hospital stays, overall postoperative complications, postoperative stress incontinence, mesh erosion and effectiveness between the two groups.; Conclusion: The current study showed comparable efficacy between RASC and LSC. Though RASC was associated with less blood loss and a lower conversion rate, the differences were not clinically significant. The choice of surgical procedure with either RASC or LSC is according to surgeon discretion and patient preferences. (© 2021. The International Urogynecological Association.)

Chang, C. S., et al. (2023). "Comparison of Minimally Invasive and Open Surgery for the Treatment of Endometrial Cancer with a High Risk of Recurrence: A Propensity Score Matching Study in Korea and Taiwan." Annals of Surgical Oncology 30(11): 6855-6864.
	Background: This study compared oncologic outcomes between minimally invasive surgery (MIS) and open surgery for the treatment of endometrial cancer with a high risk of recurrence. Method(s): This study included patients with endometrial cancer who underwent primary surgery at two tertiary centers in Korea and Taiwan. Low-grade advanced-stage endometrial cancer (endometrioid grade 1 or 2) or endometrial cancer with aggressive histology (endometrioid grade 3 or non-endometrioid) at any stage was considered to have a high risk of recurrence. We conducted 1:1 propensity score matching between the MIS and open surgery groups to adjust for the baseline characteristics. Result(s): Of the total of 582 patients, 284 patients were included in analysis after matching. Compared with open surgery, MIS did not show a difference in disease-free survival [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.67-1.77, P = 0.717] or overall survival (HR 0.67; 95% CI 0.36-1.24, P = 0.198). In the multivariate analysis, non-endometrioid histology, tumor size, tumor cytology, depth of invasion, and lymphovascular space invasion were risk factors for recurrence. There was no association between the surgical approach and either recurrence or mortality in the subgroup analysis according to stage and histology. Conclusion(s): MIS did not compromise survival outcomes for patients with endometrial cancer with a high risk of recurrence when compared with open surgery.Copyright © 2023, Society of Surgical Oncology.

Chang, E. S., et al. (2022). "Postprocedural Pain Associated With 5 Versus 20 Intradetrusor Injections of onabotulinumtoxinA for Treatment of Overactive Bladder: a Multicenter Randomized Clinical Trial." Urogynecology (Philadelphia, Pa.) 28(8): 518‐525.
	IMPORTANCE: Intradetrusor injection of onabotulinumtoxinA is performed via varying injection paradigms but no studies have studied the various effects of these paradigms on patient experience with the procedure. OBJECTIVES: This randomized clinical trial aims to compare pain and procedure time between patients receiving a 100‐unit dose of onabotulinumtoxinA in 5 injections compared to 20 injections for the treatment of idiopathic overactive bladder or urgency urinary incontinence. STUDY DESIGN: Patients presenting with refractory overactive bladder or urgency urinary incontinence at 2 clinical sites were identified and randomized to undergo onabotulinumtoxinA treatment with 5 injections versus 20 injections. Patients rated their pain level on a 10‐point visual analog scale at procedure completion. The procedure duration was recorded with a stopwatch. Patients were followed up 6 weeks postprocedure, at which time they completed a Global Response Assessment to determine subjective efficacy of treatment. Participants were additionally monitored for incidence of adverse events in the follow‐up period. RESULTS: The average pain score was not statistically significant between groups (2; interquartile range, 1‐4 for the 5 injection group vs 3; interquartile range, 2‐4 for the 20 injection group; P = 0.27). Patients who received 5 injections experienced significantly shorter mean procedure time as compared with patients who received 20 injections (76 seconds vs 176 seconds; P < 0.001). There were no differences in subjective efficacy or adverse events between groups. CONCLUSIONS: Perceived pain, efficacy, and postprocedure complications did not significantly differ between patients receiving 5 injections and 20 injections, but procedure time was significantly shorter.

Chang, N. (2022). "Effects of Fuyuan Yishen Huoxue decoction combined with conventional western medicine in treatment of irregular menstruation after induced abortion." China Minkang Medicine / 中国民康医学 34(14): 107‐109,113.
	Objective: To observe the effect of Fu Yishen Huoxue Decoction combined with conventional western medicine in the treatment of patients with irregular menstruation after induced abortion. Methods: From January 2018 to January 2020, 80 patients with irregular menstruation after induced abortion were selected for prospective study, and they were divided into the control group and the observation group with 40 cases in each group according to the random number table method. The control group was treated with conventional western medicine (estradiol valerate tablets + progesterone capsules), and the observation group was treated with Fufu Yishen Huoxue Decoction on the basis of the control group. Thickness, menstrual period, estrogen levels [estradiol (E_(2)), progesterone (P)], and incidence of adverse reactions. Results: The total effective rate of the observation group was 95.00% (38/40), which was higher than 75.00% (30/40) of the control group, and the difference was statistically significant (P<0.05). Conclusion: Fu Yishen Huoxue Decoction combined with conventional western medicine in the treatment of patients with irregular menstruation after induced abortion can improve the total effective rate of treatment, estrogen level, promote endometrial hyperplasia, and restore menstrual cycle, and its effect is better than conventional western medicine treatment.

Chang, O. H., et al. (2021). "03 Surgical correction of the genital hiatus at the time of sacrocolpopexy - are concurrent posterior repairs cost-effective?" American Journal of Obstetrics and Gynecology 224(6 Supplement): S726-S727.
	Objectives: Correcting the genital hiatus with posterior repair (PR) during sacrocolpopexy reduces prolapse recurrence, but may result in complications or dyspareunia requiring subsequent treatment. Our objective was to perform a cost-effectiveness analysis of posterior repair performed at the time of laparoscopic sacrocolpopexy. Material(s) and Method(s): We used TreeAge Pro to construct a decision model comparing sacrocolpopexy with and without concurrent posterior repair (SCP and SCP + PR). Using a time horizon of 1 year, we modeled prolapse recurrence, prolapse retreatment, and complications including rectal injury, rectovaginal hematoma requiring OR take-back, and postoperative dyspareunia. Costs included index surgery, surgical retreatment, and complications. Costs, probabilities, and utilities were gathered from Medicare reimbursement data, published literature, and institutional billings department (Table 1). We modeled effectiveness as quality-adjusted-life years (QALY). Cost-effectiveness was defined as an incremental cost-effectiveness ratio (ICER) and willingness to pay (WTP) of $100,000/QALY. Base-case, tornado plots, sensitivity analyses were performed. Result(s): In the base case scenario, SCP was the dominant strategy with lower cost and higher effectiveness. Tornado plots showed CEA results were most influenced by the cost of SCP, cost of SCP + PR, and probability of dyspareunia after SCP. In one-way sensitivity analyses, the model outcome would change only if the cost of SCP was greater than SCP + PR or if the probability of dyspareunia was 80.8% after SCP. SCP + PR costs more than SCP, but we analyzed what would happen if costs were equal. In this hypothetical scenario, SCP + PR still only became the optimal strategy if the recurrence rate after SCP was >20% (base case 9.2%) while at the same time dyspareunia after SCP + PR was <10% (base case 29%). These unlikely scenarios further support the strength of our model. Similarly, when the probability of prolapse recurrence after SCP was increased to 30%, SCP + PR only became the optimal strategy if every patient undergoes prolapse retreatment after SCP and SCP + PR. Conclusion(s): In this cost-effectiveness analysis, SCP without concurrent PR was the dominant strategy. SCP + PR costs more with lower effectiveness than SCP alone due to higher surgical cost of SCP + PR and higher probability of dyspareunia after SCP + PR. [Formula presented]Copyright © 2021

Chang, O. H., et al. (2021). "Hysterectomy Versus Hysteropexy at the Time of Native Tissue Pelvic Organ Prolapse Repair: A Cost-Effectiveness Analysis." Female Pelvic Medicine and Reconstructive Surgery 27(2): E277-E281.
	Objective The aim of the study was to determine whether a hysterectomy at the time of native tissue pelvic organ prolapse repair is cost-effective for the prevention of endometrial cancer. Methods We created a decision analysis model using TreeAge Pro. We modeled prolapse recurrence after total vaginal hysterectomy with uterosacral ligament suspension (TVH-USLS) versus sacrospinous ligament fixation hysteropexy (SSLF-HPXY). We modeled incidence and diagnostic evaluation of postmenopausal bleeding, including risk of endometrial pathology and diagnosis or death from endometrial cancer. Modeled costs included those associated with the index procedure, subsequent prolapse repair, endometrial biopsy, pelvic ultrasound, hysteroscopy, dilation and curettage, and treatment of endometrial cancer. Results TVH-USLS costs US $587.61 more than SSLF-HPXY per case of prolapse. TVH-USLS prevents 1.1% of women from experiencing postmenopausal bleeding and its diagnostic workup. It prevents 0.95% of women from undergoing subsequent major surgery for the treatment of either prolapse recurrence or suspected endometrial cancer. Using our model, it costs US $2,698,677 to prevent one cancer death by performing TVH-USLS. As this is lower than the value of a statistical life, it is cost-effective to perform TVH-USLS for cancer prevention. Multiple 1-way sensitivity analyses showed that changes to input variables would not significantly change outcomes. Conclusions TVH-USLS increased costs but reduced postmenopausal bleeding and subsequent major surgery compared with SSLF-HPXY. Accounting for these differences, TVH-USLS was a cost-effective approach for the prevention of endometrial cancer. Uterine preservation/removal at the time of prolapse repair should be based on the woman's history and treatment priorities, but cancer prevention should be one aspect of this decision.Copyright © American Urogynecologic Society. All rights reserved.

Chang, O. H., et al. (2021). "Reply: Hysterectomy Versus Hysteropexy at the Time of Native-Tissue Pelvic Organ Prolapse Repair: A Cost-Effectiveness Analysis." Female Pelvic Medicine & Reconstructive Surgery 27(12): e716.
	
Chang, O. H., et al. (2022). "Surgical correction of the genital hiatus at the time of sacrocolpopexy - a 7-year markov analysis." American Journal of Obstetrics and Gynecology 226(3 Supplement): S1291.
	Objectives: Narrowing the genital hiatus with a posterior repair at the time of sacrocolpopexy may reduce the odds of prolapse recurrence but increases the risk of surgical complications or dyspareunia. Our objective was to perform a cost-effectiveness analysis of concurrent posterior repair performed at the time of laparoscopic hysterectomy with sacrocolpopexy over a 7-year time period. Material(s) and Method(s): We used TreeAge Pro to construct a decision model comparing sacrocolpopexy with and without concurrent posterior repair (SCP and SCP+PR) over a time horizon of 7 years. A Markov model was embedded in the decision model to simulate prolapse recurrence, prolapse retreatment, and complications including rectal injury, rectovaginal hematoma requiring operative take-back, and postoperative dyspareunia. Costs included index surgery, surgical retreatment and complications. Costs, probabilities, and utilities were gathered from Medicare reimbursement data, published literature, and institutional billings department (Table 1). We modeled effectiveness as quality-adjusted-life years (QALY). Cost-effectiveness was defined as an incremental cost-effectiveness ratio (ICER) calculated as costs / effectiveness and the willingness to pay (WTP) was set at $100,000/QALY. Sensitivity analyses were performed by varying input variables across a wide range to identify thresholds where our conclusions could change. Result(s): Our model showed that SCP was the dominant strategy with lower costs (-$ 9699.02) and higher effectiveness (+0.10) compared to SCP+PR over the 7-year period. Tornado plots showed that the analysis was most influenced by the cost of SCP and cost of SCP+PR. In one-way sensitivity analyses, the model outcome would change only if the cost of SCP was greater than SCP+PR which is not reasonable with the longer operative time and associated surgical complications. In two-way sensitivity analyses, we varied the probability of prolapse recurrence after both strategies. Our conclusions would only change if the probability of recurrence after SCP was 49.5% higher than after SCP+PR. When varying the probabilities of dyspareunia for both strategies, SCP+PR only became the dominant strategy if the probability of dyspareunia for SCP+PR were 9.9% less than the rate associated with SCP alone. None of the scenarios above were reasonable. Conclusion(s): In this 7-year Markov cost-effectiveness analysis, SCP without concurrent PR was the dominant strategy. SCP+PR costs more with lower effectiveness than SCP alone due to higher surgical cost of SCP+PR and higher probability of dyspareunia after SCP+PR. [Formula presented]Copyright © 2022

Chang, W. Y. and H. Y. Li (2020). "Anesthetic efficacy of propofol combined butorphanol in laparoscopic surgery for ectopic pregnancy: A protocol of systematic review and meta-Analysis." Medicine (United States) 99(20): e20289.
	Background:Recent studies have suggested that propofol combined butorphanol (PB) has anesthetic effect in laparoscopic surgery (LS) for ectopic pregnancy (EP). But investigations of its potential effects are inconsistent. We will explore the current literature examining PB in LS for EP. Method(s):We will perform a comprehensive search from MEDLINE, Embase, Cochrane Library, PsycINFO, Global Health, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure from inception to the present. Other literatures, such as conference abstracts, references to the relevant reviews will also be checked. Two authors will check the titles, abstracts, and full texts independently. They will also independently carry out data collection and study quality assessment. We will conduct statistical analysis using RevMan 5.3 software. Result(s):This study will provide accurate results on the anesthetic effect and safety of PB in LS for EP. Conclusion(s):This study will establish high-quality evidence of the anesthetic effect and safety of PB in LS for EP to facilitate the clinical practice and guideline development.Study registration number:INPLASY202040044.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Chang, Y., et al. (2022). "Association of embryo transfer type with infertility in endometriosis: a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics 39(5): 1033-1043.
	Purpose: The study aims to evaluate whether frozen embryo transfer can restore optimal receptivity leading to better assisted reproductive technology outcomes in women with endometriosis.; Methods: This systematic review and meta-analysis, conducted from January 10, 2021 to July 1, 2021, searched the Cochrane Library, PubMed, Embase, Web of Science, OVID, and Clinicaltrials.gov databases from inception to January 10, 2021. The search strategy combined search terms as follows: ("endometriosis" OR "deep endometriosis" OR "endometrioma") AND ("frozen-thawed embryo transfer" OR "frozen embryo transfer" OR "freeze-all strategy") AND ("pregnancy outcome" OR "live birth rate" OR "clinical pregnancy rate" OR "miscarriage rate"). No publication time or language limits were set during the searches. In addition, references of the related articles were searched by hand. Patients were included if they had a history of endometriosis and had received fresh or frozen embryo transfer. Only the first transfer cycle was included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to express outcomes, and data synthesis was conducted using RevMan, version 5.4 software.; Results: A total of six studies with moderate methodologic quality were retrieved in the meta-analysis. The studies included 3010 women with endometriosis who wanted to conceive; 1777 (59.0%) had frozen embryo transfer, and 1233 (41.0%) had fresh embryo transfer. There was a significantly higher frequency of live births in the frozen embryo group than in the fresh embryo group (OR, 1.53; 95% CI, 1.13-2.08; P = .007). Despite a similar clinical pregnancy rate in the two groups (OR, 1.26; 95% CI, 0.95-1.69; P = .11), the difference in miscarriage rate was significant (OR, 0.70; 95% CI, 0.50-0.97; P = .03). Evidence quality was considered moderate.; Conclusion: Cryopreserved embryo transfer has resulted in preferable reproduction outcomes when compared with fresh embryo transfer in patients with endometriosis, but the evidence is not yet abundant. More strictly designed research is needed to evaluate whether frozen embryo transfer leads to better reproductive outcomes in women with endometriosis compared with those receiving fresh embryo transfer.; Registration Number: PROSPERO CRD42021248313. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chang, Y. S., et al. (2023). "Associations between breastfeeding intention, breastfeeding practices and post-natal depression during the COVID-19 pandemic: A multi-country cross-sectional study." Maternal & child nutrition 19(1): e13450.
	Associations between breastfeeding intention, duration and post-natal depression (PND) have been shown in pre-COVID-19 studies. However, studies during COVID-19 have not examined the associations between breastfeeding intention, breastfeeding practices, and PND in an international sample of post-natal women, taking into consideration COVID-19 related factors. This is the first study to address this gap as both PND and breastfeeding may be affected by COVID-19, and have important long-term effects on women's and infant's health. A cross-sectional internet-based survey was conducted with 3253 post-natal women from five countries: Brazil, South Korea, Taiwan, Thailand, and the United Kingdom from July to November 2021. The results showed that women who intended to breastfeed during pregnancy had lower odds of having PND than women who did not intend to. Women who had no breastfeeding intention but actually breastfed had greater odds (AOR 1.75) of having PND than women who intended to breastfeed and actually breastfed. While there was no statistical significance in expressed breast milk feeding in multivariable logistic regression models, women who had shorter duration of breastfeeding directly on breast than they planned had greater odds (AOR 1.58) of having PND than those who breastfed longer than they planned even after adjusting for covariates including COVID-19-related variables. These findings suggested the importance of working with women on their breastfeeding intention. Tailored support is required to ensure women's breastfeeding needs are met and at the same time care for maternal mental health during and beyond the pandemic.

Chao, Y.-S. and S. McCormack (2019). "HPV Self-Sampling for Primary Cervical Cancer Screening: A Review of Diagnostic Test Accuracy and Clinical Evidence – An Update." CADTH Rapid Response Reports.
	The introduction of cervical cancer screening and timely intervention is associated with the recent decrease in cervical cancer incidence. 1 There are several options to screen cervical cancer. Two of the methods commonly used in Canada are cytology and human papillomavirus (HPV) tests. 2 Cytology requires clinicians to obtain samples from the cervix for further examination. 2 HPV tests that detect the infection of HPV also requires samples from the cervix. 2 The HPV tests that detect certain types of carcinogenic HPV genotypes, especially genotypes 16 and 18, are called high-risk HPV tests. 3 The samples can be obtained via brushes or swabs or other devices not only by clinicians, but also by screening participants. 3 Clinician-sampled HPV tests are used in screening program in several countries, such as Italy 4 and Denmark. 5 Self-sampled HPV tests have been tested in the capital region in Denmark but have not replaced clinician-sampled tests. 5 With feasibility to conduct at home and potentially better acceptability to participants, self-sampled HPV tests have been used to reach individuals that are unscreened or under-screened for cervical cancer. 4 In a previous CADTH report, there was some evidence to show similar diagnostic test accuracy between self- and clinician-sampled HPV tests. 6 For example, the diagnostic test accuracy of GP5+/6+ polymerase chain reaction (PCR) HPV tests using samples taken with brushes is similar for self- and clinician-collected samples. 7 In several primary studies, fair to high agreement between self- and clinician-sampled HPV tests has been found. 6 Since the previous CADTH review, there have been primary studies comparing self- and clinician-sampled HPV tests published 8 , 9 and a systematic review has been updated. 3 This report updates the previous review on the difference in the diagnostic test accuracy of self-sampled HPV tests and the agreement between self- and clinician-sampled HPV tests. (Copyright © 2019 Canadian Agency for Drugs and Technologies in Health.)

Chaowawanit, W., et al. (2021). "Comparison between laparoscopic and robotic surgery for sentinel lymph node mapping in endometrial cancer using indocyanine green and near infra-red fluorescence imaging." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 41(4): 642-646.
	Indocyanine green (ICG) and near infra-red fluorescence imaging in minimally invasive surgery is an option to map sentinel lymph nodes (SLN). The aim of this study was to compare the outcomes of SLN mapping between laparoscopic and robotic surgery. One-hundred-and-forty women with histologically confirmed endometrial cancer, were treated with a minimally invasive hysterectomy, bilateral salpingo-oophorectomy and SLN mapping. After anaesthetic induction, ICG was superficially injected into cervical submucosa and deeply injected into the cervical stroma at the 3 and 9 o'clock positions (1.25 mg/site). Eleven cases were abandoned after ICG injection (laparoscopic surgery seven cases and robotic surgery four cases) because of obesity, technical difficulty and peritoneal disease. One-hundred-and-eleven patients were analysed. Seventy-six patients had a laparoscopic procedure and 33 patients had robotic surgery. The overall and bilateral detection rates were 97% and 83% for laparoscopic surgery and 88% and 73% for robotic surgery. Laparoscopic surgery was superior to robotic surgery in terms of overall detection (p-value .046). There was no significant difference in the intra-operative SLN identification time or SLN dissection time between laparoscopy and robotic surgery (p-value .247 and .145, respectively). Further research is required to compare laparoscopy and robotic surgery in terms of SLN detection.Impact StatementWhat is already known on this subject? Sentinel lymph node (SLN) mapping aims to avoid complications and provide useful staging information for endometrial cancer. ICG has been shown to improve the detection rate and NPV compared with other tracers (blue dye and technetium 99). No data exists comparing SLN mapping rates using ICG in laparoscopy and robotic surgery.What do the results of this study add? The overall and bilateral detection rates were 97% and 83% for laparoscopic surgery and 88% and 73% for robotic surgery. Laparoscopic surgery was superior to robotic surgery in terms of overall detection. There was no significant difference in the intra-operative SLN identification time or SLN dissection time between laparoscopy and robotic surgery.What are the implications of these findings for clinical practice and/or further research?: This study confirms that laparoscopy and robotic surgery are not different in terms of bilateral detection rate and SLN operating time; the study population is small.

Chapman, G. C., et al. (2021). "Tamsulosin vs placebo to prevent postoperative urinary retention following female pelvic reconstructive surgery: a multicenter randomized controlled trial." American Journal of Obstetrics and Gynecology 225(3): 274.e271-274.e211.
	BACKGROUND: Postoperative urinary retention is common after female pelvic reconstructive surgery. Alpha receptor antagonists can improve dysfunctional voiding by relaxing the bladder outlet and may be effective in reducing the risk of postoperative urinary retention. OBJECTIVE: This study aimed to determine whether tamsulosin is effective in preventing postoperative urinary retention in women undergoing surgery for pelvic organ prolapse. STUDY DESIGN: This was a multicenter, double-blind, randomized controlled trial between August 2018 and June 2020, including women undergoing surgery for pelvic organ prolapse. Patients were excluded from recruitment if they had elevated preoperative postvoid residual volume, history of postoperative urinary retention, or a contraindication to tamsulosin. Those who experienced cystotomy were excluded from analysis. Participants were randomized to a 10-day perioperative course of tamsulosin 0.4 mg vs placebo, beginning 3 days before surgery. A standardized voiding trial was performed on postoperative day 1. The primary outcome was the development of postoperative urinary retention, as defined by the failure of the voiding trial or subsequent need for catheterization to empty the bladder. Secondary outcomes included the rate of urinary tract infection and the impact on lower urinary tract symptoms as measured by the American Urological Association Symptom Index. RESULTS: Of 119 patients, 57 received tamsulosin and 62 received placebo. Groups were similar in regard to demographics, preoperative prolapse and voiding characteristics, and surgical details. Tamsulosin was associated with a lower rate of postoperative urinary retention than placebo (5 patients [8.8%] vs 16 patients [25.8%]; odds ratio, 0.28; 95% confidence interval, 0.09-81; P=.02). The number needed to treat to prevent 1 case of postoperative urinary retention was 5.9 patients. The rate of urinary tract infection did not differ between groups. American Urological Association Symptom Index scores significantly improved after surgery in both groups (median total score, 14 vs 7; P<.01). Scores related to urinary stream improved more in the tamsulosin group than in placebo (P=.03). CONCLUSION: In this placebo-controlled trial, tamsulosin use was associated with a reduced risk of postoperative urinary retention in women undergoing surgery for pelvic organ prolapse.

Chaput Kathleen, H., et al. (2023). "Effect of Remote Peer-Counsellor- delivered Behavioral Activation and Peer-support for Antenatal Depression on Gestational Age at Delivery: a single-blind, randomized control trial." Trials 24(1): 240.
	Background: Antenatal depression (AD) is the most common complication of pregnancy in developed countries and increases the risk of preterm birth (PTB). Many pregnant individuals with AD do not obtain treatment due in part to risks associated with antidepressant medications, the expense and wait times for psychological services, and perceived stigma. Accessible and timely treatment of antenatal depression is crucial to minimize foetal impacts and associated long-term child health outcomes. Previous studies show that behavioural activation and peer support are promising avenues of treatment for perinatal depression. Additionally, remote and paraprofessional counselling interventions show promise as more accessible, sustainable, and cost-effective treatment avenues than traditional psychological services. The primary aim of this trial is to test the effectiveness of a remote, behavioural activation and peer support intervention, administered by trained peer para-professionals, for increasing gestational age at delivery among those with antenatal depression. The secondary aims are to evaluate the effectiveness for treating AD prior to delivery, with persistence into the postpartum; improving anxiety symptoms; and improving parenting self-efficacy compared to controls.; Methods: A two-arm, single-blinded, parallel groups randomized controlled trial (RCT) with repeated measures will be conducted. Participants scoring >10 on the Edinburgh Postnatal Depression Scale will be recruited from the larger P3 cohort and invited to enroll. Assessments will be conducted prior to 27 weeks' gestation at trial intake (T1), post-intervention, prior to delivery (T2), 5-6 months postpartum (T3), and 11-12 months postpartum (T4) and will include self-report questionnaires and linked medical records.; Discussion: Our remote, peer paraprofessional-delivered behavioural activation plus peer support intervention has the potential to successfully reduce symptoms of AD, which may in turn decrease the risk of PTB and subsequent health impacts. The current trial builds on previous findings and uses a patient-oriented approach to address priorities for patient care and to provide a cost-effective, accessible, and evidence-based treatment to pregnant individuals with AD.; Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) registry (ISRCTN51098220) ISRCTN51098220. Registered on April 7, 2022. (© 2023. The Author(s).)

Charbonneau-Lefebvre, V., et al. (2022). "Attachment and Childhood Maltreatment as Moderators of Treatment Outcome in a Randomized Clinical Trial for Provoked Vestibulodynia." The Journal of Sexual Medicine 19(3): 479-495.
	Background: Although distal developmental factors, such as attachment and childhood maltreatment (CM), are associated with the occurrence, severity, and adjustment to provoked vestibulodynia (PVD)-the most prevalent form of vulvodynia-no studies to date have examined whether these variables are related to treatment efficacy in the context of PVD. Attachment and CM may act as moderating variables when examining different treatment modalities, whereby individuals with more insecure attachment orientations (anxiety/avoidance) or a history of CM may benefit less from treatments with higher interpersonal contexts, such as sex and couple therapy-a recommended treatment for PVD.; Aim: The present randomized clinical trial (RCT) examined attachment and CM as predictors and moderators of sexual satisfaction, distress, and function at post-treatment and 6-month follow-up while comparing 2 treatments for PVD: Topical lidocaine, and a novel cognitive behavioral couple therapy focused on women's pain and partners' sexuality.; Methods: One hundred eight women with PVD were randomized to a 12-week treatment of either lidocaine or couple therapy. Women completed questionnaires at pretreatment, post-treatment, and at a 6-month follow-up.; Outcomes: (1) Global Measure of Sexual Satisfaction; (2) Female Sexual Distress Scale-Revised; (3) Female Sexual Function Index.; Results: Both attachment and CM were significant moderators of treatment outcomes. At either post-treatment or 6-month follow-up, in the couple therapy condition, women with greater attachment avoidance had poorer outcomes on sexual distress, satisfaction and function, whereas women with higher levels of CM had poorer outcomes on sexual satisfaction and sexual function, compared to women in the lidocaine condition.; Clinical Implications: Although these novel findings need further replication, they highlight the importance for clinicians to take into account distal factors, for instance, attachment and CM, when treating sexual difficulties such as PVD, as these variables may affect more interpersonal dimensions of treatment (eg, trust, compliance, etc.) and ultimately, treatment progress.; Strengths & Limitations: Using a rigorous RCT study design and statistical approach, this study is the first to examine attachment and CM as moderators in the treatment of sexual difficulties. It is however limited by the use of self-report measures, and further studies are necessary to validate the generalizability of current results to other sexual difficulties.; Conclusion: Findings support the role of interpersonal factors in the treatment of PVD and indicate that short-term psychological interventions, such as couple therapy, may be less beneficial for women with antecedents of CM and attachment insecurity. V Charbonneau-Lefebvre, M-P Vaillancourt-Morel, NO Rosen, et al. Attachment and Childhood Maltreatment as Moderators of Treatment Outcome in a Randomized Clinical Trial for Provoked Vestibulodynia. J Sex Med 2022;19:479-495. (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Charite, U., et al. (2021). Transcranial Direct Current Stimulation to Reduce Chronic Pelvic Pain in Endometriosis.
	No Results Available Device: tDCS : Transcranial direct current stimulation Pelvic pain via pressure pain threshold Female Phase 2 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment EA1/174/19 January 2023

Charite, U., et al. (2021). Effects of Fasting on Success Rates of Assisted Reproductive Techologies.
	No Results Available Behavioral: Fasting Fertilisation rate|glucose in culture medium of oocytes|lactate in culture medium of oocytes|pyruvate in culture medium of oocytes|pregnancy rate|rate of mature oocytes|rate of life births|rate of implantable embryos|Course of IVF/ICSI preparation and pregnancy|WHO-5 questionnaire|changes in diet|mindfulness|anxiety and depression|current mood|experienced stress|physical fitness|quality of relationship|psychological stress caused by the unfulfilled desire to have children|gratitude|self-efficacy|abdominal sonography Female Not Applicable 1 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment KiWuC December 12, 2022

Charles, U. and R. Czech (2022). Study Comparing Transobturator Cystocele vs. Anterior Vaginal RepairS.
	No Results Available Procedure: Transobturator cystocele repair|Procedure: Anterior colporrhaphy Anatomic failure|Composite surgery failure|2-year composite surgery failure|2-year anatomic failure|Complication rate|Pain after the surgery|Subjective perception of improvement|2-year subjective perception of improvement|Patient satisfaction|De novo stress urinary incontinence (SUI)|De novo overactive bladder (OAB)|Change in quality of life - urinary incontience|Change in quality of life - prolapse bother|Change in quality of life - anorectal problems|Change in quality of sexual life|Change in severity of urinary incontinence Female Not Applicable 592 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment STARS November 1, 2025

Charlotte, M., et al. (2024). "Implementation of robotic ups (unilateral pectineal suspension) for the correction of apical prolapse in a high volume laparoscopy center." European Journal of Obstetrics and Gynecology and Reproductive Biology 293: 40.
	Introduction and aims: Pelvic organ prolapse (POP) is a common disorder. Conservative treatment can be addressed; if unsuccessful, surgery is indicated. Surgical treatments such as vaginal hysterectomy (with anterior and posterior repair), sacrospinous fixation and laparoscopic sacrocolpopexy are broadly used as standard surgical procedures. Performing a hysterectomy does not increase the success rate. In addition, the use of synthetic meshes is under debate because of possible postoperative complications. The study aims to describe the implementation of UPS as a minimal invasive mesh-free apical fixation in a high volume laparoscopy center. Method(s): Robotic UPS is a standardized technique of 5 steps to restore the natural anatomical position of the uterus or vaginal cuff. After identifying the cranial part of the pectineal ligament, a non-absorbable suture is placed for lateral fixation. By manipulation of the uterus or cuff intraoperatively, the ideal anatomical reconstruction is simulated. After dissecting the bladder, the medial fixation of the suture is placed, followed by a tension free suspension to restore the physiological anatomy. Prolapse was measured by POP-Q. Result(s): In comparison to the standard surgical techniques for POP, UPS provides several advantages. The medial tension-free apical placement combined with normal pelvic floor mobility and the restoration of the vaginal axis allows for normal vaginal function. The technique provides maximum safety, significant reduction of operative time and avoidance of ureter, bowel and hypogastric nerve dissection. This procedure can be performed in a same day discharge setting (SDS). Conclusion(s): UPS was first designed, described and performed at the University Pelvic Floor Center of Klinikum Nuernberg, Germany. UPS is a highly efficient minimal-invasive mesh-free surgery, avoiding the need of a hysterectomy. Reliable level one support is achieved, respecting the natural anatomy. This technique can easily be implemented, resulting in efficient and innovative surgical POP treatment.Copyright © 2023

Charo Lindsey, M., et al. (2022). "Real-World Data From a Molecular Tumor Board: Improved Outcomes in Breast and Gynecologic Cancers Patients With Precision Medicine." JCO precision oncology 6: e2000508.
	Purpose: Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes.; Methods: Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes.; Results: Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS ( P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance.; Conclusion: Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.; Competing Interests: Ramez N. EskanderConsulting or Advisory Role: Pfizer, Clovis Oncology, AstraZeneca/MedImmune, Tesaro, Merck, Eisai, Agenus, Myriad Genetics, Daiichi Sankyo/LillySpeakers' Bureau: AstraZeneca/MedImmune, Myriad GeneticsTravel, Accommodations, Expense: AstraZeneca/MedImmune, Merck, Eisai Jason SicklickStock and Other Ownership Interests: PersonalisConsulting or Advisory Role: DecipheraSpeakers' Bureau: QED Therapeutics, Foundation Medicine, Roche, Deciphera, MJH Life SciencesResearch Funding: Foundation Medicine, Amgen Richard SchwabLeadership: Procend IncStock and Other Ownership Interests: Samumed (I)Patents, Royalties, Other Intellectual Property: The patent covers sialylated glycans and antibodies that specifically bind to them for early detection and diagnosis of cancer (Inst) Rebecca ShatskyHonoraria: SOTERIA Precision Medicine, Horizon CME, OncoSec, Relevate Health Group, The Dedham GroupConsulting or Advisory Role: SOTERIA Precision Medicine, OncoSec, The Dedham GroupSpeakers' Bureau: Horizon CMEResearch Funding: Oncternal Therapeutics (Inst), Phoenix Molecular Designs (Inst), Genentech (Inst), OncoSec (Inst), CytomX Therapeutics (Inst), Merck (Inst) Steven PlaxeStock and Other Ownership Interests: Pfizer, Merck, Zimmer BioMet, GlaxoSmithKline, AstraZeneca, Bristol Myers Squibb/Pfizer, Johnson & Johnson/JanssenResearch Funding: Endocyte (Inst), Incyte (Inst), MedImmune (Inst), Novartis (Inst), Pfizer (Inst), Janssen Oncology (Inst), BIND Therapeutics (Inst), PharmaMar (Inst), AstraZeneca (Inst), Kevelt (Inst), Millennium (Inst), Tesaro (Inst) Shumei KatoHonoraria: RocheConsulting or Advisory Role: Foundation Medicine, Pfizer/EMD SeronoResearch Funding: ACT Genomics, Sysmex, Konica Minolta, OmniSeq Razelle KurzrockLeadership: CureMatch, CureMetrix IncStock and Other Ownership Interests: CureMatch, IDbyDNAHonoraria: Roche, EUSA Pharma, NeoGenomics Laboratories, Biocom, NeoMed Therapeutics, Advanced Therapeutics, LEK, AACR, Chugai Pharma USA, Wiley, Merck, Pfizer, Meyer Consulting, Foundation Medicine, Turning Point Therap utics, BicaraConsulting or Advisory Role: Actuate Therapeutics, Loxo, XBiotech, Neo-Med, Roche, Gaido Soluventis, Pfizer, Merck, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics IncSpeakers' Bureau: RocheResearch Funding: Guardant Health (Inst), Sequenom (Inst), Merck Serono (Inst), Genentech (Inst), Pfizer (Inst), Foundation Medicine (Inst), Incyte (Inst), Konica Minolta (Inst), Grifols (Inst), OmniSeq (Inst), Debiopharm Group (Inst), Boerhinger Ingelheim (Inst), Top Alliance BioScience (Inst), Takeda (Inst), MedImmune (Inst)Travel, Accommodations, Expenses: Roche, EUSA Pharma, NeoGenomics Laboratories, Biocom, NeoMed Therapeutics, Advanced Therapeutics, LEK, AACR, Chugai Pharma USA, WileyNo other potential conflicts of interest were reported.

Charoenkwan, K., et al. (2024). "Alterations in mitochondria isolated from peripheral blood mononuclear cells and tumors of patients with epithelial ovarian cancers." Scientific Reports 14(1): 15.
	Metabolic alterations play an essential role in ovarian carcinogenesis. The flexibility of mitochondrial functions facilitates cellular adaptation to the tough environment associated with carcinogenesis. An understanding of the differences in mitochondrial functions in normal ovaries and cancers could provide a basis for further exploration of future mitochondria-based screening, diagnosis, prognostic prediction, and targeted therapy for epithelial ovarian cancers. The main objective of this study was to assess mitochondrial function profiles measured from PBMCs and ovarian tissues of epithelial ovarian cancers in comparison with normal ovaries. A total of 36 patients were recruited for the study, all of whom underwent primary surgical treatment for malignant epithelial ovarian neoplasm. Of these, 20 patients were in the early stage and 16 patients were in the advanced stage. Additionally, 21 patients who had pelvic surgery for benign gynecologic conditions, with normal ovaries incidentally removed, were recruited as controls. At the time of surgery, a blood sample was collected from each participant for PBMC isolation, and ovarian tissue was retained for molecular studies. These studies included the examination of oxidative stress, mitochondrial mass, mitochondrial respiration, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, and mitochondrial swelling. Clinical and histopathological data were also collected and compared between different stages of epithelial ovarian cancers: early-stage (group 1), advanced-stage (group 2), and normal ovaries (group 3). The levels of cellular oxidative stress, mitochondrial mass, and mitochondrial biogenesis in the peripheral blood mononuclear cells (PBMCs) of participants with ovarian cancer were significantly lower than those of the control group. However, the mitochondrial respiratory parameters measured from the PBMCs were similar across all three groups. Furthermore, mitochondrial membrane depolarization and mitochondrial swelling were observed in ovarian tissues of both early-stage and advanced-stage cancer groups. We demonstrated the dynamic nature of mitochondrial ROS production, biogenesis, and respiratory function in response to epithelial ovarian carcinogenesis. The flexibility of mitochondrial functions under diverse conditions may make it a challenging therapeutic target for ovarian cancer.Copyright © 2024. The Author(s).

Charra-Brunaud, C., et al. (2022). "[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]." Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique 26(3): 474-480.
	Purpose: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers.; Material and Methods: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy.; Results: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications.; Conclusion: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer. (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Charrie, M. and S. Billecocq (2021). "Knowledge of pelvic floor disorders in peripartum women: A systematic review." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 31(4): 204-214.
	
Chase, D., et al. (2020). "Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 30(5): 596-601.
	Introduction: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab.; Methods: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240.; Results: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain.; Discussion: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.; Competing Interests: Competing interests: DC reports personal fees received from AstraZeneca, Clovis, Roche/Genentech, and Tesaro, outside of the submitted work. BJM reports personal fees received from Roche/Genentech, outside of the submitted work. RTP reports serving on a Scientific Advisory Board for Genentech/Roche. AO reports serving on advisory boards for Roche, AstraZeneca, PharmaMar, Clovis Oncology, and Tesaro and received support for travel/accommodation from Roche, AstraZeneca, and PharmaMar. WKH reports receiving personal fees as consultant for Antiva, PathoVax, and Li-Cor, outside of the submitted work. DR reports serving on the Advisory Board for Genentech and Ipsen and received personal fees, outside of the submitted report. RS reports serving on the Speaker Bureau for Genentech as well as serving on Advisory Boards for Tesaro, Clovis, AstraZeneca, and Ethicon, outside of the submitted work. KST reports serving on the Speaker’s Bureau, Advisory Board for Roche/Genentech. (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Chase, D. M., et al. (2021). "Impact of disease progression on healthrelated quality of life of advanced ovarian cancer (AOC) patients-pooled analysis from the prima trial." International Journal of Gynecological Cancer 31(SUPPL 1): A284.
	Introduction/Background∗ Clinical trials consistently demonstrate the detrimental impact of progressive disease (PD) on patients' health‐related quality of life (HRQoL). Progressionfree survival (PFS) is an established regulatory endpoint. However, PFS is often excluded as an efficacy endpoint on the basis that ‐ PFS is not patient relevant ‐ in early benefit assessment by select EU health technology agencies. The PRIMA/ENGOT‐OV26/GOG‐3012 (NCT02655016) Phase 3 trial showed niraparib significantly prolongs median PFS vs placebo in patients with AOC responsive to 1L platinum (Pt)‐ based chemotherapy, (CT), regardless of biomarker status. This post‐hoc analysis of PRIMA is the first study to examine the relationship between HRQoL and PD in a broad frontline AOC maintenance treatment setting. Methodology In PRIMA, patients with AOC responsive to 1L Pt CT were randomised 2:1 to once‐daily, maintenance niraparib or placebo. Impact of PD on patient HRQoL, irrespective of treatment, was evaluated within the pooled ITT population by comparing HRQoL at the last on‐treatment (pre‐progression) visit with HRQoL at end of treatment (EOT), +4 weeks, +8w, +12w, and +24w. Assessments included FOSI, EORTC QLQ‐C30, EQ‐5D‐VAS, and EORTC QLQ‐OV28 abdominal/GI symptom scale. ANCOVA was applied with treatment as a fixed effect and HRQoL at last on‐treatment visit as a continuous covariate. Mixed models for repeated measurements (MMRM) evaluated cumulative HRQoL changes. Result(s)∗ Significant reductions in HRQoL from pre‐ to postprogression were observed across all measures. Compared with pre‐progression, FOSI scores (Least‐squares mean [95% CI]) were lower at EOT+4w (‐2.2 [‐2.8, ‐1.6]) and EOT+24w (‐ 1.7 [‐2.3, ‐1.1]); each p<0.0001. Similarly, at these timepoints EORTC‐QLQ‐C30 scores were lower by ‐10.2 (‐12.4, ‐8.0) and ‐10.7 (13.2, ‐8.2) points, respectively, and EQ‐5D‐VAS by ‐8.2 (‐10.4, ‐6.0) and ‐6.2 (‐8.2, ‐4.2) points, respectively; each p<0.0001. EORTC QLQ‐OV28 scores were significantly worse at EOT+4w (6.6 [4.3, 8.9]) and EOT+24w (5.0 [2.8, 7.2]); each p<0.0001. Similar changes were seen on MMRM analysis. Conclusion∗ These findings demonstrate HRQoL is negatively impacted by PD in AOC. Preservation of HRQoL, an important therapy goal in the maintenance setting particularly for asymptomatic patients, can be achieved with PFS prolongation. PFS is of significant relevance and clinically important for AOC patients.

Chau, J. P. C., et al. (2022). "Perioperative enhanced recovery programmes for women with gynaecological cancers." Cochrane Database of Systematic Reviews 2022(3): CD008239.
	Background: Gynaecological cancers account for 15% of newly diagnosed cancer cases in women worldwide. In recent years, increasing evidence demonstrates that traditional approaches in perioperative care practice may be unnecessary or even harmful. The enhanced recovery after surgery (ERAS) programme has therefore been gradually introduced to replace traditional approaches in perioperative care. There is an emerging body of evidence outside of gynaecological cancer which has identified that perioperative ERAS programmes decrease length of postoperative hospital stay and reduce medical expenditure without increasing complication rates, mortality, and readmission rates. However, evidence-based decisions on perioperative care practice for major surgery in gynaecological cancer are limited. This is an updated version of the original Cochrane Review published in Issue 3, 2015. Objective(s): To evaluate the beneficial and harmful effects of perioperative enhanced recovery after surgery (ERAS) programmes in gynaecological cancer care on length of postoperative hospital stay, postoperative complications, mortality, readmission, bowel functions, quality of life, participant satisfaction, and economic outcomes. Search Method(s): We searched the following electronic databases for the literature published from inception until October 2020: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PubMed, AMED (Allied and Complementary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and four Chinese databases including the China Biomedical Literature Database (CBM), WanFang Data, China National Knowledge Infrastructure (CNKI), and Weipu Database. We also searched four trial registration platforms and grey literature databases for ongoing and unpublished trials, and handsearched the reference lists of included trials and accessible reviews for relevant references. Selection Criteria: We included randomised controlled trials (RCTs) that compared ERAS programmes for perioperative care in women with gynaecological cancer to traditional care strategies. Data Collection and Analysis: Two review authors independently screened studies for inclusion, extracted the data and assessed methodological quality for each included study using the Cochrane risk of bias tool 2 (RoB 2) for RCTs. Using Review Manager 5.4, we pooled the data and calculated the measures of treatment effect with the mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with a 95% confidence interval (CI) to reflect the summary estimates and uncertainty. Main Result(s): We included seven RCTs with 747 participants. All studies compared ERAS programmes with traditional care strategies for women with gynaecological cancer. We had substantial concerns regarding the methodological quality of the included studies since the included RCTs had moderate to high risk of bias in domains including randomisation process, deviations from intended interventions, and measurement of outcomes. ERAS programmes may reduce length of postoperative hospital stay (MD -1.71 days, 95% CI -2.59 to -0.84; I2 = 86%; 6 studies, 638 participants; low-certainty evidence). ERAS programmes may result in no difference in overall complication rates (RR 0.71, 95% CI 0.48 to 1.05; I2 = 42%; 5 studies, 537 participants; low-certainty evidence). The certainty of evidence was very low regarding the effect of ERAS programmes on all-cause mortality within 30 days of discharge (RR 0.98, 95% CI 0.14 to 6.68; 1 study, 99 participants). ERAS programmes may reduce readmission rates within 30 days of operation (RR 0.45, 95% CI 0.22 to 0.90; I2 = 0%; 3 studies, 385 participants; low-certainty evidence). ERAS programmes may reduce the time to first flatus (MD -0.82 days, 95% CI -1.00 to -0.63; I2 = 35%; 4 studies, 432 participants; low-certainty evidence) and the time to first defaecation (MD -0.96 days, 95% CI -1.47 to -0.44; I2 = 0%; 2 studies, 228 participants; low-certainty evidence). The studies did not report the effects of ERAS programm s on quality of life. The evidence on the effects of ERAS programmes on participant satisfaction was very uncertain due to the limited number of studies. The adoption of ERAS strategies may not increase medical expenditure, though the evidence was of very low certainty (SMD -0.22, 95% CI -0.68 to 0.25; I2 = 54%; 2 studies, 167 participants). Authors' conclusions: Low-certainty evidence suggests that ERAS programmes may shorten length of postoperative hospital stay, reduce readmissions, and facilitate postoperative bowel function recovery without compromising participant safety. Further well-conducted studies are required in order to validate the certainty of these findings.Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Chekerov, R., et al. (2023). "Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ)." Journal of Cancer Research and Clinical Oncology 149(10): 7637-7649.
	Purpose: Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC).; Methods: Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m 2 (day 1, 8, 15, ever 28 days) for six cycles to identify the maximum tolerated dose (MTD) of Pazopanib added in a dose-escalating scheme with 400 mg starting dose. The phase II analysed safety and efficacy aspects. For all patients with clinical remission a maintenance with Pazopanib until progression was allowed. This trial is registered with ClinicalTrials.gov, number NCT01600573.; Results: Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3-4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0-5.0). Due to early progression only 20% of the patients were able to start with maintenance treatment.; Conclusion: The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit. (© 2023. The Author(s).)

Chekerov, R., et al. (2022). "COMPARISON OF QUALITY OF LIFE IN PATIENTS WITH PLATINUM-SENSITIVE RECURRENT OVARIAN, FALLOPIAN TUBE AND PERITONEAL CANCER TREATED WITH TRABECTEDIN PLUS PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) OR STANDARD PLATINUM-BASED THERAPY: DATA LOOK OF THE NOGGO S16/ COMPASS TRIAL." International Journal of Gynecological Cancer 32(Supplement 2): A252-A253.
	Introduction/Background Despite recent progress regarding surgical and medical management of primary ovarian cancer, relapses are still frequent and one of the most critical challenges in the clinical routine. There is a broad consensus that quality of life (QoL) should be one of the most relevant goals of any therapy in relapsed ovarian cancer. Methodology We report the results of a data look of the multicentre, randomized (1:1), active-controlled, open-label phase IV NOGGO-S16/COMPASS trial performed in patients with recurrent, platinum-sensitive, ovarian, peritoneal or fallopian tube cancer. The scope of this trial is to evaluate QoL with EORTC QLQ-C30 and QLQ-OV28 questionnaires during/after chemotherapy either with platinum/taxane-free combination of trabectedin (Yondelis) plus PLD or with standard platinumbased chemotherapy comprising combination of carboplatin with PLD, gemcitabine or paclitaxel. The current data look serves to characterise the included patient population. Results Data from 76 patients screened have been analysed. Patients have a median age of 63 years (range: 21-82), the performance status score of 0/1 was recorded in 75 patients (98.7%), and most are BRCA-negative (77.4%). They are diagnosed with primary ovarian carcinoma (83.6%), primary peritoneal carcinoma (9.6%) and fallopian carcinoma (6.8%), and 79% of patients have a grade 3 histopathological staging. Poly (ADP-ribose) polymerase inhibitors or bevacizumab were given as prior maintenance therapy to 15.3% and 76.4% of patients, respectively. Overall, 60% of patients had a platinum- free interval of >12 months before randomization and 45.8% of patients finished COMPASS trial as per protocol. The main reasons for withdrawal were progression under treatment (18.6%), toxicity (15.3%), death (13.6%) and patient wish (6.8%). Post-protocol maintenance therapy was given to 23.8% of patients. No differences in patient characteristics were observed. Conclusion Based on this data look no significant signal for a non-inferiority of the study arms have been observed. Study is ongoing and open for recruitment.

Chelariu-Raicu, A., et al. (2021). "A multicenter open-label randomized phase II trial of paclitaxel plus EP-100, a novel LHRH receptor-targeted, membrane-disrupting peptide, versus paclitaxel alone for refractory or recurrent ovarian cancer." Gynecologic Oncology 160(2): 418-426.
	OBJECTIVE: This randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor. METHODS: In a limited "run-in" dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m2, 20 mg/m2, 30 mg/m2). In the randomized phase, patients received weekly paclitaxel (80 mg/m2 intravenously) plus twice weekly EP-100 (30 mg/m2 intravenously; combination arm) or weekly paclitaxel alone (80 mg/m2 intravenously; paclitaxel arm). The primary study endpoint was overall response rate (ORR). RESULTS: Forty-four patients were then randomized to either the experimental combination arm (n = 23) or the standard of care paclitaxel monotherapy arm (n = 21). The ORR was 35% (95%CI 16%-57%) for the combination arm and 33% (95% CI 15%-57%) for the paclitaxel arm. An interesting observation from an unplanned analysis was that a subset of patients with target liver lesions showed a greater overall response rate to the combination (69%) compared to paclitaxel alone (16%). The frequency of treatment-related grade 3-4 adverse events was similar between treatment arms: 48% vs 43% for the combination and paclitaxel arms, respectively. CONCLUSIONS: ORR in the EP-100 combination arm was similar to that in the group treated with paclitaxel alone; however, a subset of patients with liver metastases appeared to benefit from the combination. The addition of EP-100 did not appear to augment the adverse event profile of paclitaxel and was well tolerated.

Chen, B., et al. (2020). "The Effect of Neoadjuvant Chemotherapy on Lymph Node Metastasis of FIGO Stage IB1-IIB Cervical Cancer: A Systematic Review and Meta-Analysis." Frontiers in Oncology 10: 570258.
	Objectives: This study aimed to assess the effect of neoadjuvant chemotherapy (NACT) on the rate of lymph node metastasis (LNM) in FIGO stage IB1-IIB cervical cancer patients and compare the LNM between NACT plus surgery and surgery only.; Methods: We identified 34 eligible studies in PubMed, Web of Science, Cochrane Library, and EMBASE from inception to July 27, 2019. Data analyses were performed by Stata (version 13) and Revman (version 5.3).; Results: In these 34 included studies, the pooled incidence of LNM was estimated as 23% (95% CI, 0.20-0.26; I 2 = 79.6%, P <0.001). In the subgroup analysis, we identified five factors, including study type, year of publication, continents from which patients came, histological type and the FIGO stage. When taking FIGO stage into consideration, the LNM rate was 13% in stage IB (95% CI: 0.10-0.15; I 2 = 5.5%, P =0.385), 23% in stage IIA (95% CI: 0.18-0.28; I 2 = 0%, P =0.622), and 27% in stage IIB (95% CI: 0.20-0.33; I 2 = 0%, P =0.898), respectively. Through the comparison between NACT plus surgery and surgery only based on the six randomized controlled trials, the incidence of positive lymph nodes was lower in patients receiving NACT plus surgery than surgery only (RR=0.57, 95% CI: 0.39-0.83; I 2 = 60.5%, P =0.027). The 5-year OS was higher in the NACT + surgery group than surgery-only group (RR=1.13, 95% CI: 1.03-1.23; I 2 = 0.0%, P =0.842).; Conclusions: Among cervical cancer in stage IB1-IIB, the preoperative NACT plus radical surgery resulted in a 23% probability of LNM, which was lower than those receiving radical surgery only. In stage IIA and IIB, the effect of NACT to reduce LNM was more obvious. (Copyright © 2020 Chen, Wang, Ren, Shen, Ding, Zhu, Mao and Wang.)

Chen, C., et al. (2023). "Effectiveness of digital psychological interventions in reducing perinatal depression: a systematic review of meta-analyses." Archives of Women's Mental Health 26(4): 423-439.
	Digital psychological interventions have been widely used clinically in recent years, but the methodological quality and quality of evidence of related studies are unclear, thus interfering with the translation of practice outcomes and the application of clinical decisions. We searched for meta-analyses of randomized controlled trials in the PubMed, Web of Science, Embase, Cochrane Library, JBI Database, CINAHL, and PsycINFO databases as well as some databases containing gray literature up to 27 April 2022 using a combination of keywords. After two researchers independently screened and extracted data from the literature, the methodological quality of the included literature was evaluated by the AMSTAR 2 scale, and the evidence quality of the outcome index was graded by the Grading of Recommendations, Assessment, Development, and Evaluation system. A total of 12 meta-analyses reporting the positive impact of digital psychological interventions in the prevention and/or treatment of depressive symptoms in perinatal women were included, but the methodological quality and evidence level of the included studies were low. Digital psychological interventions are effective in reducing perinatal depression, but the methodological quality and reliability of outcome indicators are mostly low. Improving study designs, using higher-quality clinical evidence, conducting systematic evaluation studies strictly following the procedures, and standardizing the reporting of study results are recommended.

Chen, D., et al. (2020). "Pregnancy Outcomes Following Letrozole Use in Frozen-thawed Embryo Transfer Cycles: A Systematic Review and Meta-analysis." Geburtshilfe und Frauenheilkunde 80(8): 820-833.
	While widely used for ovulation induction in assisted reproductive technology, the clinical efficacy of letrozole for endometrial preparation prior to frozen-thawed embryo transfer (FET) cycles remains yet to be elucidated. We performed a meta-analysis to compare pregnancy outcomes after letrozole use with those of other endometrial preparation protocols in patients undergoing FET. PubMed, Scopus, Embase and the Cochrane Library were searched for eligible studies. Clinical pregnancy rate (CPR), live birth rate (LBR) and birth defect rate (BDR) were analysed using odds ratio (OR) and 95% confidence interval (CI). A total of 10 studies representing 75 968 FET cycles were included. Comparable CPR and LBR were observed when comparing letrozole administration with natural cycle (OR 1.24, 95% CI: 0.69 - 2.24; OR 1.18, 95% CI: 0.60 - 2.32), artificial cycle (OR 1.46, 95% CI: 0.87 - 2.44; OR 1.39, 95% CI: 0.77 - 2.52), and artificial cycle with gonadotropin-releasing hormone agonist suppression (OR 1.11, 95% CI: 0.78 - 1.59; OR 1.18, 95% CI: 0.82 - 1.68). Pooled results of the limited studies comparing letrozole with human menopausal gonadotropin demonstrated a similar CPR between groups (OR 1.46, 95% CI: 0.29 - 7.21, two studies), but the letrozole group had a statistically lower LBR (OR 0.67, 95% CI: 0.52 - 0.86, one study). No increased BDR was observed in the letrozole group compared to natural cycles or artificial cycles (OR 0.98, 95% CI: 0.60 - 1.61; OR 1.39, 95% CI; 0.84 - 2.28). This pooled analysis supports the use of letrozole as an efficacious and safe alternative to mainstream regimens for endometrial preparation in FET cycles.; Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Chen, F., et al. (2021). "Evaluation of the Efficacy of Sex Hormone-Binding Globulin in Insulin Resistance Assessment Based on HOMA-IR in Patients with PCOS." Reproductive sciences (Thousand Oaks, Calif.) 28(9): 2504-2513.
	This study aimed to evaluate the efficacy of SHBG in predicting insulin resistance (IR) in newly diagnosed, untreated patients with polycystic ovary syndrome (PCOS). Hundred newly diagnosed, untreated patients with PCOS and 61 subjects without PCOS (41 healthy volunteers with normal BMI and 20 subjects with overweight/obese) were included in the study. Receiver-operating characteristic (ROC) analysis was used to assess the effectiveness of SHBG in predicting IR in overweight/obese and non-overweight PCOS patients and the optimal cut-off values of SHBG. The results showed negative correlations between log-SHBG and log-I0 (r = - 0.372, P < 0.001) and log-SHBG and log-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r = - 0.393, P < 0.001) after adjusting for blood pressure, serum lipid, age, and body mass index (BMI) in all of the PCOS patients. In patients with IR (defined as HOMA-IR ≥2.29), the area under the ROC curves (AUCs) of the SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.774 (P = 0.0001), 0.922 (P = 0.0001), and 0.885 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 37 nmol/L with a sensitivity of 97.62% and specificity of 80.85% in the overweight group. In patients with IR (HOMA-IR ≥2.5), the AUCs of SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.741 (P = 0.0003), 0.928 (P = 0.0001), and 0.880 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 30.2 nmol/L with a sensitivity of 97.44% and specificity of 82.69% in the overweight/obese group. In conclusion, this study observed a negative correlation between SHBG and HOMA-IR in PCOS patients after adjustment of confounding factors. SHBG was an independent influential factor of HOMA-IR and can be used as a positive predictive marker for IR in PCOS patients, especially in those who are overweight/obese.

Chen, F., et al. (2022). "Multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira) as a novel treatment in patients with high-grade squamous intraepithelial lesion: APRICITY phase 3 study protocol." BMJ Open 12(6): e061740.
	Introduction: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL.; Methods and Analysis: Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints).; Ethics and Dissemination: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations.; Trial Registration Number: NCT04484415; clinicaltrials.gov.; Competing Interests: Competing interests: CD received consulting fees from MSD, GSK, Tesaro and Clovis Oncology and honoraria from MSD and GSK. LH is an employee of Asieris Pharmaceuticals (Shanghai) Co., Ltd. FC, ZN, CM, LS, YZ, ZY, JL and PH have nothing to declare. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chen, F., et al. (2021). "A multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira) as a novel treatment in patients with high grade squamous intraepithelial lesion: APRICITY Phase 3 study protocol." MedRxiv.
	Introduction: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. Objective(s): APRICITY is a multicentre, prospective, double-blind, randomised controlled Phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug- and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive therapy for women with HSIL. Methods and analysis: Patients with biopsy-confirmed HSIL histology are invited to participate in the study currently being conducted at 47 sites in China and 25 sites in Ukraine, Russia and European Union. The aim is to include at least 384 patients which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low grade squamous intraepithelial lesion (LSIL). Primary endpoint is the proportion of the responders at 6 months after first treatment. Secondary efficacy endpoints and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints for Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study following patients for further 6 months to collect additional efficacy and safety data (study extension endpoints). Conclusion(s): Due to its non-invasiveness and convenient application, Cevira may be a favourable alternative to surgical methods in treatment of patients with HSIL. Ethics and dissemination: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations.Copyright © , CC BY-NC.

Chen, F. Y., et al. (2019). "New therapeutic approaches for endometriosis besides hormonal therapy." Chinese Medical Journal 132(24): 2984-2993.
	Objective:Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosisData sources:Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials.gov, and Google Scholar were searched up to October 2019, using search terms "endometriosis" and "non-hormonal therapy."Study selection:Twenty-four articles were reviewed for analysis, including nine animal studies and 15 human trials; all were published in English. Result(s):Twenty-four articles were identified, including 15 human trials with 861 patients and nine animal studies. Some agents have been evaluated clinically with significant efficacy in endometriosis-related pelvic pain and subfertility, such as rofecoxib, etanercept, pentoxifylline, N-palmitoylethanolamine, resveratrol, everolimus, cabergoline (Cb2), and simvastatin. Other drugs with similar pharmacological properties, like parecoxib, celecoxib, endostatin, rapamycin, quinagolide, and atorvastatin, have only been tested in animal studies. Conclusion(s):Clinical data about most of the non-hormonal agents are not sufficient to support them as options for replacement therapy for endometriosis. In spite of this, a few drugs like pentoxifylline showed strong potential for real clinical application.Copyright © 2019 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license. Copyright © 2019 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

Chen, H. (2023). "Study on the efficacy of organic corrosion inhibitor in acid medium as complex in thetreatment of systemic diseases in patients with gynecological tumors." European Journal of Gynaecological Oncology 44(2): 129-130.
	Objectives: Common gynecological tumors are vulva skin tumor, cervical tumor, and uterine fibroids, etc. At present, there is still no uniform standard for the causes of cancer and the mechanism of recurrence and metastasis. If the treatment of gynecological tumor patients is not timely, it is easy to cause cancer. But there will be a variety of diseases, the mortality rate is high. Although traditional chemotherapy can reduce the relevant symptoms of patients, there are often adverse reactions and recurrence and metastasis after surgery. How to effectively prevent tumor metastasis and recurrence is one of the key research directions of anti-tumor. Therefore, in this study, organic corrosion inhibitors in acidic media were used as complexes to implant into the organ section after tumor resection to ensure tumor metastasis and recurrence. Method(s): 83 patients with gynecological tumors in a hospital from September 2021 to April 2022 were selected as the research objects. After screening the inclusion criteria, 70 patients were selected for the control experiment. In the control experiment, the average course of gynecological cancer patients was 5 years, and the average tumor diameter was (20 +/- 13) mm. 70 patients were divided into two groups, 35 patients in each group. The first group was the control group for routine treatment, and the second group was the experimental group for implantation of organic corrosion inhibitor complex for treatment after surgery. The data were analyzed by SPSS22.0 software. The statistical method was t-test, and p < 0.05 was the difference with statistical significance. Result(s): During the study, 70 patients were subject to a control experiment. In the control experiment, the adverse reactions and recurrence rate in the control group were higher than those in the experimental group, and the adverse reactions in the control group reached 17 cases, accounting for 48.58%. There were 8 cases of recurrence, accounting for 22.86%. There were only 9 cases of adverse reactions in the experimental group, accounting for 25.70%. 2 cases recurred, accounting for 6.66%. Specific data are shown in Table 1. In the comparison of serum indicators, the control group's Alanine Aminotransferase (ALT) is 51.4 +/- 16, and Aspartate Aminotransferase (AST) is 36 +/- 12.1. The ALT and AST of the experimental group were 53 +/- 18 and 42 +/- 16. There is a significant difference between the two groups in the level of indicators. The specific results are shown in Fig. 1. Conclusion(s): This study demonstrated that a new organic corrosion inhibitor with appropriate cost was applied to gynecological tumor patients as a complex. The experimental results showed that the complex effectively changed the clinical serum indexes of patients. The rate of adverse reactions was lower, and the rate of tumor recurrence and metastasis was lower than that of traditional chemotherapy. It is a safe treatment method with wide clinical application..

Chen, H., et al. (2021). "Efficacy and Safety of Bevacizumab-Combined Chemotherapy for Advanced and Recurrent Endometrial Cancer: A Systematic Review and Meta-analysis." Balkan Medical Journal 38(1): 7-12.
	Background: Bevacizumab-combined chemotherapy is a new regimen for advanced/recurrent endometrial cancer.; Aims: To evaluate the efficacy and safety of bevacizumab-combined chemotherapy in advanced/recurrent endometrial cancer.; Study Design: Systematic review and meta-analysis.; Methods: Eligible studies were retrieved from Embase, PubMed, and Cochrane Library. The data of primary outcomes including progression-free survival and overall survival and secondary outcomes including overall survival, response rate, and adverse events (grade ≥2) were extracted, pooled, and used for the meta-analysis to compare the efficacy and safety of bevacizumab-combined chemotherapy with other treatments in patients with advanced/recurrent endometrial cancer.; Results: Notably, 2 randomized-controlled and 5 single-arm trials of bevacizumab-combined chemotherapy or bevacizumab single-agent therapy for endometrial cancer were included. Meta-analysis indicated that bevacizumab-combined chemotherapy significantly increased the progression-free survival rate (hazard ratio=0.82, 95% confidence interval=0.70, 0.97) and overall survival rate (hazard ratio=0.83, 95% confidence interval=0.70, 0.98) compared with chemotherapy alone. The rates of overall, complete, and partial response to bevacizumab-combined chemotherapy were 76%, 22%, and 21%, respectively. The 6 and 12-month disease-free progression rates after bevacizumab-combined chemotherapy were 79% and 62%, respectively. Anemia (23%), leukopenia (46%), neutropenia (51%), hypertension (16%), and fatigue (24%) were the general adverse events after bevacizumab-combined chemotherapy.; Conclusion: Bevacizumab-combined chemotherapy may have a higher efficacy in improving the overall and progression-free survival in patients with advanced/recurrent endometrial cancers compared with chemotherapy alone.

Chen, J., et al. (2021). "Systematic review on efficacy and safety of Bushen Tiaojing therapy in treatment of polycystic ovary syndrome infertility." Chinese Traditional and Herbal Drugs 52(10): 3037-3050.
	Objective: To systematicly evaluate the efficacy and safety of Bushen Tiaojing Recipes combined with ovulation-induction drugs in the treatment of polycystic ovary syndrome (PCOS) infertility. Method(s): Databases including CNKI, VIP, Wan Fang, PubMed, Cochrane Library, Embase and Clinical Trials were searched from the establishment of the database to November, 2020. According to the inclusion and exclusion criteria, the randomized controlled trials (RCTs) of Bushen Tiaojing Recipes combined with ovulation-induction drugs in the treatment of PCOS infertility were collected, the data were extracted, and the quality of each study was evaluated with the "Cochrane bias risk assessment tool". The Meta analysis of the final indicators was analyzed by the Review Manager 5.3 software and the quality of evidence of the outcome indicators were evaluated according to the GRADE standard. Result(s): A total of 28 RCTs with 2659 patients and 1337 cases in the treatment group and 1322 cases in the control group were enrolled. Systematic review results showed that: compared with single ovulation-induction drugs, Bushen Tiaojing Recipes combined with ovulation-induction drugs had significant effects on improving ovulation rate, pregnancy rate and androgen (T), luteinizing hormone (LH), reducing the incidence of adverse reactions and ovarian volume and increasing endometrial thickness (P < 0.01). There was no significant difference in increasing estradiol (E2) and follicle stimulating hormone (FSH) between the two groups (P > 0.05). The funnel plot of ovulation rate and pregnancy rate showed that each research point was asymmetric, suggesting that there might be publication bias. According to the GRADE method, the quality of evidence was low in ovulation rate and pregnancy rate and very low in other aspects. Conclusion(s): Under the guidance of Bushen Tiaojing method, Bushen Tiaojing Recipes combined with ovulation induction drugs has fine clinical efficacy and good safety. However, due to the low quality of the included studies, clinical use still needs to be cautious.Copyright © 2021, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Chen, J.-M., et al. (2022). "Clinical Evaluation of Autologous and Allogeneic Stem Cell Therapy for Intrauterine Adhesions: A Systematic Review and Meta-Analysis." Frontiers in Immunology 13: 899666.
	Objective: Intrauterine adhesions (IUAs) are a major cause of female infertility. Stem cells can be used to restore endometrial function owing to their regenerative abilities. We compared the safety and efficacy of autologous and allogeneic stem cell treatments in patients with recurrent IUA after conventional therapy based on a systematic review of the related literature.; Methods: The PubMed, Embase, and Cochrane databases were systematically searched. All analysis were performed using Review Manager 5.4. We compared improvements in endometrial thickness, pregnancy rates, menstruation, and side effects after autologous and allogeneic stem cell therapy. The study was registered with PROSPERO, CRD 42022322870.; Results: Our search returned 154 reports, 10 of which met the inclusion criteria, representing 116 patients. Of these, 44 patients in two studies were treated with allogeneic stem cells and 72 patients in eight studies were treated with autologous stem cells. Improvements in endometrial thickness and pregnancy rates after intrauterine device treatment were compared between the autologous and allogeneic stem cell groups. Endometrial thickness increased more after autologous stem cell IUA treatment (mean difference, 1.68; 95% confidence interval [CI]: 1.30-2.07; P < 0.00001), and the pregnancy rate was also improved (relative risk, 1.55; 95% CI: 1.19-2.02, P < 0. 001). No obvious and serious adverse reactions were observed during stem cell therapy in either group.; Conclusions: This meta-analysis and systematic review of the results of randomized trials of autologous and allogeneic stem cell treatments for IUA suggests that autologous stem cells have a better effect in improving the endometrium thickness and pregnancy rate.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022322870.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chen, Huang, Chen, Lin and Shi.)

Chen, J. S. and K. A. Kho (2021). "22 Randomized trial of laparoscopic versus abdominal hysterectomy for benign indications and impact on surgical success." American Journal of Obstetrics and Gynecology 224(6): S741.
	Objectives: To examine the differences in patient‐centered goals in individuals undergoing laparoscopic versus abdominal hysterectomy for benign indications. Materials and Methods: This abstract is a sub‐analysis of a prospective, randomized controlled trial examining the impact of laparoscopic versus abdominal hysterectomy on patient‐centered outcomes including quality of life, pain, and productivity. At each pre‐operative visit, each participant reported top three patient‐centered goals they hoped to achieve prior to undergoing a hysterectomy. In addition, participants rated their subjective achievement of goals from 1 to 10, with 1 (goal not achieved) and 8 to 10 (goal achieved). The subjects were then randomized to total laparoscopic (TLH) or total abdominal hysterectomy (TAH). Following surgery, repeat assessment of goal achievement was obtained within each group on post‐operative day 1, at 6 weeks, 6 months than 12 months post‐operatively. In addition, the length of time to successful goal achievement (scores of 8 or higher during any post‐operative period) was recorded in all participants. Power analysis was based on differences in the primary outcome of the initial study: Quality of Life as scored by the SF‐36 form. With a clinically significant differences of 15 points in the SF‐36 required a sample size of 29 patients in each group for a power of 80% with a two‐sided significance level of 0.05. With that, differences in goal achievement rates and the length of time to goal achievement were examined between TLH and TAH groups using the calculated sample size of the initial study. Results: A total of 91 participants undergoing benign hysterectomy were enrolled and randomized. Three patients were lost to follow‐up, with 88 subjects available for final analysis. The top three goals listed respectively were: “Abnormal Uterine Bleeding,” (AUB) “Pelvic Pain,” (PP) and “Quality of Life.” (QOL). Overall, there were no significant differences in the percentage of goal achievement between TLH and TAH groups for QOL (69% vs 67%, P = 0.88), for AUB (67% vs 51%, P = 0.14), and PP (53% vs 49%, P = 0.67), though it appears that participants who listed QOL as their top goal were more likely to achieve the goal. The mode of hysterectomy did not appear to alter differences in goal achievement. In addition, there were no significant differences in the length of time to goal achievement between TLH and TAH groups for QOL (156 days vs 159 days, P = 0.99), for AUB (96 vs 116, P = 0.25), and PP (146 vs 143, P = 0.80). Conclusion: In conclusion, there were no significant differences in goal achievement rates between TLH versus TAH groups regardless of the desired patient‐centered goals, though the majority of participants achieved their respective goals in both groups. In addition, there were no differences in length of time to goal achievement between the two groups. This study suggests that a hysterectomy itself may have a therapeutic effect on patient‐centered outcomes irrespective of the route of surgery.

Chen, K., et al. (2023). "Efficacy and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage: a systematic review and meta-analysis." Frontiers in Pharmacology 14: 1138968.
	Background: Despite some progress has been made in the pathogenesis and treatment of threatened miscarriage (TM), conventional treatment remains suboptimal. Thus, complementary medicine gradually become a new treatment option for treating threatened miscarriage. Gushen Antai Pills ( GAP), a classic prescription of Traditional Chinese medicine (TCM), has became a popular complementary therapy to conventional western medicine (dydrogesterone) in treating threatened miscarriage in recent years. However, a systematic summary and analysis for its therapeutic effects is lacking. This meta-analysis aimed to systematically evaluate the effectiveness and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage. Methods: A systematic search across seven electronic databases was conducted from inception to 17 September 2022. Studies were included if they were randomized controlled trials (RCTs) evaluating the effect of integrating Gushen Antai Pills and dydrogesterone in patients with threatened miscarriage, and reported the outcomes of interest. All statistical analyses were conducted using the Revman5.3 and Stata 13 software. The GRADE system was used to evaluate the quality of evidence. Results: Ten eligible randomized controlled trials involving 950 participants were contained in this meta-analysis. The pooled analysis showed that Gushen Antai Pills combined with dydrogesterone can significantly reduce the incidence of early pregnancy loss (RR: 0.29; 95% CI: 0.19-0.42; p < 0 . 00001) and alleviate clinical symptoms (RR: 1.39; 95% CI: 1.22-1.59; p < 0 . 00001), compared with treatment of dydrogesterone alone. Also, meta-analysis indicated that integrating Gushen Antai Pills and dydrogesterone is more effective than using dydrogesterone alone in improving hormone levels (serum levels of progesterone, β -HCG and estradiol) for women with threatened miscarriage (all p < 0 . 00001). Meanwhile, the combined effects with significant heterogeneity also showed favorable consistency in the sensitivity analyses, indicating a good stability of present results. Moreover, no significant differences between Gushen Antai Pills combined with dydrogesterone and control group on adverse events was identified. The overall GRADE qualities were low to moderate. Conclusion: The overall available evidence suggested that Gushen Antai Pills combined with dydrogesterone had significant effects in improving pregnancy success rate, clinical symptoms and hormone levels for women with threatened miscarriage, with considerable safety and reliability. However, due to the partial heterogeneity, suboptimal quality and high risk of bias of some included studies, further rigorously designed randomized controlled trials are required. Systematic Review Registration: identifier https://INPLASY2022120035, https://inplasy.com/inplasy-2022-12-0035/.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Chen, Liu, Meng, Li, Yang and Wang.)

Chen, L., et al. (2023). "The effects of weight loss-related amenorrhea on women's health and the therapeutic approaches: a narrative review." Annals of Translational Medicine 11(2): 132.
	Background and Objective: Weight loss-related amenorrhea is defined as the reversible functional inhibition of the hypothalamic-pituitary-ovarian (HPO) axis associated with weight loss or low body weight, which occurs mostly in adolescents and women of reproductive age. The specific pathological mechanisms of this disease have not yet been elucidated, and the optimal evidence-based guidelines for its clinical assessment and management are limited. This review summarizes its adverse effects on female health, and the individualized, emerging, and multidisciplinary therapeutic approaches used to treat it. Method(s): We searched the PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases for Chinese and English literature on functional hypothalamic amenorrhea (FHA), and retrieved original articles (on basic and clinical research) and reviews published up to December 2022. Key Content and Findings: We reviewed the findings on the unfavorable effects of weight loss-related amenorrhea with a focus on reproduction, the skeletal and cardiovascular system, other endocrine effects, and mental health. Lifestyle changes and hormonal replacement have been shown to alleviate the underlying causes and lead to the recovery of menstruation. However, the efficacy of treatments is affected by many factors, such as psychological stress and heterogeneity. Conclusion(s): Weight loss-related amenorrhea, which is an important type of FHA, is manifested by anovulation and hypoestrogenism, and has both short- and long-term adverse effects on women's overall health. It is difficult to alleviate its underlying causes. Individualized treatments need to be optimized and emerging or multidisciplinary therapeutic approaches need to be explored that aim to recover normal menstruation and ovulation, eliminate the undesirable effects of prolonged hypoestrogenism and alleviate psychological disorders.Copyright © Annals of Translational Medicine. All rights reserved.

Chen, L., et al. (2023). "Efficacy and safety of different low-molecular-weight heparins in improving pregnancy outcomes in patients with recurrent abortion: a network meta-analysis." Chinese Journal of Evidence-Based Medicine 23(7): 790-796.
	Objective To systematically evaluate the efficacy and safety of different low-molecular-weight heparins (LMWHs) in improving pregnancy outcomes in patients with recurrent abortion. Methods The PubMed, EMbase, Cochrane Library, CBM, CNKI, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) related to the objectives from inception to July 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 16.0 software. Results A total of 25 RCTs involving 4 631 patients were included. Enoxaparin, dalteparin, nadroparin, and tinzaparin were included. The results of network meta-analysis showed that the live birth rate of the tinzaparin was higher than that of enoxaparin and dalteparin. The live birth rate in nadroparin was higher than that in enoxaparin and dalteparin. The cumulative sorting probability showed that tinzaparin ranked best for improving the live birth rate, nadroparin ranked best for reducing the miscarriage rate, and enoxaparin ranked best for reducing the preterm birth rate. Conclusion Current evidence suggests that tinzaparin and nadroparin may be the best choice for improving pregnancy outcomes in patients with recurrent abortion. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.Copyright © 2023 West China University of Medical Science. All rights reserved.

Chen, L., et al. (2022). "A PHASE 1, FIRST IN HUMAN, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY OF TST005 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS." Journal for Immunotherapy of Cancer 10(Supplement 2): A801.
	Background Anti-programmed death 1/ligand 1 (PD-1/PD-L1) therapies have been established as standard treatment for multiple tumor types. However, the key challenge of these therapies is resistance caused by immunosuppressive factors in the tumor microenvironment (TME). TGF-b is a multi-functional cytokine that is involved in the tight regulation of either antitumor immunity or tumor immunosuppression. TGF-b promotes an immune exclusion TME thus renders PD-L1 blockade ineffective. Therefore, dual targeting PD-L1 and TGF-b represents a rational synergistic strategy to enhance clinical outcome relative to each agent alone. TST005 is a novel bi-functional fusion protein combining a high affinity PD-L1 monoclonal antibody (mAb) in a fragment crystallizable (Fc) silenced immunoglobulin G1 (IgG1) backbone and a differentiated transforming growth factor beta (TGF-b) trap with improved stability. This study will investigate TST005's safety, tolerability and preliminary anti-tumor activity in solid tumors. Methods This Phase 1, first in human (FIH) study is an openlabel, multicenter trial that consists of a dose escalation phase in patients with advanced solid tumors who has failed prior therapy followed by a dose expansion phase in human papillomavirus (HPV) related malignancies that is not amenable to surgeryand have received prior standard therapy(ies). The primary objectives are to evaluate the safety and tolerability and determine the maximum tolerated dose or recommended Phase 2 dose(s) of TST005. Secondary objectives include pharmacokinetic, pharmacodynamic and preliminary anti-tumor activity of TST005. The dose escalation phase comprises five dose cohorts: accelerated titration of 1 subject in the starting dose cohort (1 mg/kg), and then four dose cohorts (3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg) following classic 3+3 design. No more than one prior immune checkpoint inhibitor (ICI) treatment is allowed for eligible subjects. In the dose expansion phase, up to 30 patients with locally advanced or metastatic HPV+ malignancies, including cervical cancers, P16+ Oropharyngeal cancers, and other tumors that are known HPV+, and who are ICI treatment naive will be enrolled. Subjects will receive TST005 intravenous infusion every 3 weeks (Q3W) until disease progression per RECIST v1.1 and/ or immune RECIST or unacceptable toxicity. Subjects may continue to receive TST005 beyond RECIST v1.1 defined progression at the discretion of the Investigator. This study is ongoing at 4 sites in the US and China. As of the 30 June, 2022, the first two dose cohorts evaluation has been completed and no DLT was observed.

Chen, L.-R., et al. (2019). "Isoflavone Supplements for Menopausal Women: A Systematic Review." Nutrients 11(11).
	Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms "isoflavone" and "menopause", which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.

Chen, P., et al. (2020). "Effect of melatonin for the management of endometriosis: A protocol of systematic review and meta-analysis." Medicine 99(22): e20353.
	Background: This study aims to explore the effect of melatonin for the management of endometriosis.; Methods: We will search electronic databases (Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) from their inceptions to the February 29, 2020 without language and publication time limitations. The study identification, study quality assessment, and data extraction will be undertaken by two separate researchers. We will also appraise evidence quality of main outcomes by Grading of Recommendations Assessment Development and Evaluation, and statistical analysis performance by RevMan 5.3 Software.; Results: This study will summarize up-to-date clinical evidence to investigate the effect of melatonin for the management of endometriosis.; Conclusion: This study may provide helpful evidence of melatonin for the management of endometriosis.; Systematic Review Registration: INPLASY202040093.

Chen, Q., et al. (2022). "Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer." Frontiers in Oncology 12: 858826.
	Objective: To systematically evaluate the efficacy and safety of olaparib in the treatment of recurrent platinum-sensitive ovarian cancer.; Methods: The Cochrane Library, PubMed, Chinese Biomedical Literature Database, CNKI, VIP Database, Wanfang Science and Technology Database were searched for randomized controlled trials (RCTs) of olaparib in the treatment of recurrent platinum-sensitive ovarian cancer from the establishment of each database to January 2022. Two reviewers independently evaluated the quality of the literature, extracted the data, and cross-checked the methodological quality. Meta-analysis was performed using RevMan 5.4 software.; Results: A total of 7 RCTs were included, including 2406 patients, There were 1497 patients in treatment groups and 909 patients in the control group. Meta-analysis results showed that in terms of effectiveness, the overall survival time of patients in the olaparib group [HR=1.24, 95%CI(1.06, 1.45), P=0.006]; in terms of safety, for all grades of adverse events (including nausea, fatigue, vomiting, diarrhea, abdominal pain, and headache), [HR=1.54, 95%CI(1.38, 1.71), P=0.0002], for grade 3 or higher adverse events (including nausea, fatigue, vomiting, diarrhea, abdominal pain, and headache), [HR=2.13, 95%CI(1.61, 2.81), P=0.003], there were significant differences compared with the control group, suggesting that the risk of adverse reactions in the experimental group was higher than that in the control group. Subgroup analysis showed that only abdominal pain, headache and vomiting were not statistically significant, and other adverse reactions were statistically significant.; Conclusion: Based on the existing clinical evidence, olaparib in the treatment of recurrent platinum-sensitive ovarian cancer has a longer overall survival than the control group. It is an ideal regimen, but the incidence of adverse reactions is high.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chen, Li, Zhang and Wu.)

Chen, R., et al. (2020). "The effects and costs of laparoscopic versus abdominal myomectomy in patients with uterine fibroids: a systematic review and meta-analysis." BMC surgery 20(1): 55.
	Background: Abdominal myomectomy (AM) and laparoscopic myomectomy (LM) are commonly see surgery for the uterine fibroids, several randomized controlled trials (RCTs) have compared the role of AM and LM, the results remained inconsistent. Therefore, we attempted this meta-analysis to analyze the role of LM versus AM in patients with uterine fibroids.; Methods: We searched PubMed et al. databases from inception date to July 31, 2019 for RCTs that compared LM versus AM in patients with uterine fibroids. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios(OR) or mean differences(MD) with 95% confidence intervals(CI) were calculated for each outcome by means of fixed- or random-effects model.; Results: Twelve RCTs with a total of 1783 patients were identified, with 887 patients for and 897 patients for AM. Compared with AM, LM could significantly decrease the blood loss (OR = - 29.78, 95% CI -57.62- - 0.95), shorten the duration of postoperative ileus (OR = - 10.91, 95% CI -18.72- - 3.11), reduce the length of hospital stay (OR = - 1.57, 95% CI -2.05- - 1.08), but LM was associated with longer duration of operation (OR = 16.10, 95% CI 6.52-25.67) and higher medical cost (OR = 17.61, 95% CI 7.34-27.88).; Conclusions: LM seems to be a better choice for patients with uterine fibroids, more related studies are needed to identify the role of LM and AM for the treatment of uterine fibroids.

Chen, S., et al. (2022). "Retinoids in cancer chemoprevention and therapy: Meta-analysis of randomized controlled trials." Frontiers in genetics 13: 1065320.
	Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation, apoptosis. Moreover, retinoids have been used successfully for the treatment of certain malignancies, especially acute promyelocytic leukemia (APL) in adults and neuroblastoma in children. However, retinoids have not yet been translated into effective systemic treatments for most solid cancers. Some recent studies have shown that retinoids promote tumorigenesis. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of retinoids in the chemoprevention and treatment of cancers. We performed literature search of several electronic databases, including PubMed, Embase and Cochrane Library from 2000 January to 2021 November. Various outcomes were applied to investigate the potential of retinoids for prevention and treatment of cancers. The primary outcomes in this study were disease recurrence and clinical response. The secondary outcomes included overall survival (OS), cancer development, disease progression and event-free survival. We identified 39 randomized controlled trials with 15,627 patients in this study. Our results showed that lower recurrence rate and better clinical response were obtained in retinoids treated patients with cancer or premalignancy as compared with control. The differences were statistically significant (RR = 0.85, 95% CI = 0.74-0.96, p = 0.01; RR = 1.24, 95% CI = 1.03-1.49, p = 0.02, respectively). Retinoids treatment was not associated with improvement in overall survival, cancer development, disease progression or event-free survival. Subgroup analysis conducted based on cancer type showed that patients benefited from retinoids treatment in APL, renal cell carcinoma, hepatocellular carcinoma, lung cancer, Kaposi sarcoma, and complete hydatidiform mole. No significant therapeutic effect was noted in head and neck cancer, acute myeloid leukemia (AML), melanoma, breast cancer, bladder cancer, cervical intraepithelial neoplasia (CIN) or cervical carcinoma. Subgroup analysis based on tumor classification demonstrated that retinoids group obtained a lower recurrence rate and better clinical response than control group in solid cancers. In conclusion, clinical application of retinoids was associated with reduction in disease recurrence and improvement in clinical response, illustrating that retinoids play a key role in cancer prevention and therapy. Further research is needed to broaden the utility of retinoids in other types of cancers. Systematic Review Registration: PROSPERO, identifier CRD42022296706.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chen, Hu, Tao, Xia, Wu, Cheng and Wang.)

Chen, S., et al. (2022). "LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis." Frontiers in Medicine 9: 948709.
	Introduction: To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with medical treatments for women with heavy menstrual bleeding.; Materials and Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant randomized controlled trials (RCTs) in November 2021. All meta-analyses were performed using the random-effects model. PROSPERO registration number: CRD42021295379.; Results: A total of trials (with 14 references) reporting on 1,677 women were included in this systematic review. The majority of the included RCTs were rated with low-to-unclear risk of bias in selection, detection, attrition, reporting, and other bias. All RCTs were rated as high risk in performance bias because blinding was difficult to ensure in the compared groups. Results of meta-analyses revealed that the number of clinical responders was greater in the LNG-IUS group than that in the medical treatments group at both 6-month (steroidal: five RCTs; n = 490; risk ratio [RR]: 1.72 [1.13, 2.62]; I 2 = 92%; nonsteroidal: one RCT; n = 42; RR: 2.34 [1.31, 4.19]) and 12-month (steroidal: three RCTs; n = 261; RR: 1.31 [1.01, 1.71]; I 2 = 74%) endpoints, with no clear differences on number of dropouts, and the incidence of adverse events.; Conclusion: Evidence indicates that LNG-IUS is superior to the medical treatments in short-term and medium-term clinical responses, blood loss control, compliance, and satisfaction. Meanwhile, frequency of adverse events related to LNG-IUS is acceptable.; Systematic Review Registration: PROSPERO, identifier CRD42021259335, https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021295379.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chen, Liu, Peng and Zheng.)

Chen, S., et al. (2023). "Comparative study of absorbable suture and permanent suture in sacrocolpopexy: a meta-analysis and systematic review." International Urogynecology Journal 34(5): 993-1000.
	Introduction and Hypothesis: The aim of this study was to compare the surgical results and the complications of absorbable suture (AS) versus permanent suture (PS) in sacrocolpopexy (SCP).; Methods: We systematically searched PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library Central Register of Controlled Trials for articles in which researchers compared AS with PS in SCP. The primary outcomes were the surgical success rate and suture-related complications (suture exposure/erosion, mesh erosion, and suture removal). All analyses were performed with Review Manager 5.3.; Results: Four articles involving 689 patients were ultimately included. Our findings demonstrated that AS had similar surgical success rates to those of PS (OR=1.34; 95% CI, 0.60-2.96) and no significant differences in failure rates were noted between the two groups (OR=0.75; 95% CI, 0.34-1.66). Subgroup analyses in patients with anatomical failure revealed no significant differences in recurrent posterior prolapse (OR=0.33; 95% CI, 0.05-2.10) or in recurrent apical (OR=0.64; 95% CI, 0.03-13.66) or anterior prolapse (OR=0.45; 95% CI, 0.13-1.57). However, the AS group were at a lower risk of suture exposure/erosion (OR=0.18; 95% CI, 0.06-0.58) and a lower suture removal rate (OR=0.14; 95% CI, 0.03-0.61) and retreatment (OR=0.36; 95% CI, 0.16-0.82), but the mesh erosion was not significantly different (OR=1.00; 95% CI, 0.49-2.08).; Conclusions: The data showed that AS had a similar success rate, less exposure/erosion, and were less likely to be removed and require retreatment than PS, which supported the notion that AS is as effective as PS but safer. (© 2023. The International Urogynecological Association.)

Chen, X., et al. (2021). "Effects of metformin on body weight in polycystic ovary syndrome patients: model-based meta-analysis." Expert review of clinical pharmacology 14(1): 121-130.
	Objectives: The present study aimed to investigate the effects of metformin on body weight in polycystic ovary syndrome (PCOS) patients by model-based meta-analysis (MBMA).; Methods: Randomized controlled trial (RCT) studies of metformin in treatment of PCOS patients were collected and efficacy indicators were the body mass index (BMI) change rates from baseline.; Results: 28 RCT studies, 1631 PCOS patients were included for analysis. Model of metformin monotherapy, and model of metformin combination therapy were established, respectively. After deducting control group effects, the E max of metformin on BMI were -5.88% and -11.8% in metformin monotherapy and metformin combination therapy, respectively. In order to play better curative effects, for metformin monotherapy, 1000 mg/day metformin needs for at least 25.5 weeks; For metformin combination therapy, 1000 mg/day metformin needs for at least 58.6 weeks.; Conclusion: It was the first time to quantify the effects of metformin on body weight and recommend dose and duration for metformin monotherapy and metformin combination therapy in PCOS patients.

Chen, X., et al. (2022). "Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis." Frontiers in Endocrinology 13: 978280.
	Objective: The aim of this study was to evaluate the comparison between acupuncture combined with metformin versus metformin alone in improving the pregnancy rate of people with polycystic ovary syndrome (PCOS).; Methods: A literature search of eight databases resulted in nine randomized controlled trials (RCTs) that assessed the effect of acupuncture combined with metformin on pregnancy rate in PCOS patients compared with metformin alone. Subsequently, data extraction and analysis were conducted to evaluate the quality and risk of bias of the methodological design of the study, and meta-analysis was conducted on the RCT data.; Results: Nine RCTs and 1,159 women were included. Acupuncture can improve pregnancy rate. It was analyzed according to the diagnostic criteria of PCOS [ Z = 2.72, p = 0.007, relative risk (RR) 1.31, 95% CI 1.08 to 1.60, p = 0.15, I 2 = 41%]. Analysis was performed according to different diagnostic criteria of pregnancy ( Z = 3.22, p = 0.001, RR 1.35, 95% CI 1.13 to 1.63, p = 0.12, I 2 = 42%). Acupuncture can improve ovulation rate. Subgroup analysis was performed according to the number of ovulation patients ( Z = 2.67, p = 0.008, RR 1.31, 95% CI 1.07 to 1.59, p = 0.04, I 2 = 63%) and ovulation cycle ( Z = 3.57; p = 0.0004, RR 1.18, 95% CI 1.08 to 1.29, p = 0.57, I 2 = 0%). Statistical analysis also showed that acupuncture combined with metformin could improve homeostatic model assessment of insulin resistance (HOMA-IR) [mean difference (MD) -0.68, 95% CI -1.01 to -0.35, p = 0.003, I 2 = 83%].; Conclusions: Based on the results of this study, compared with metformin alone, acupuncture combined with metformin has a positive effect on pregnancy rate, ovulation rate, and insulin resistance in PCOS. However, due to the limitations regarding the number and quality of the included studies, the above conclusions need to be verified by further high-quality studies.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chen, Lan, Yang, Liu, Li, Zhu, Zhao, Long, Wang, Xie, Li and Wu.)

Chen, X., et al. (2022). "Systematic Review and Meta-Analysis of Complications after Laparoscopic Surgery and Open Surgery in the Treatment of Pelvic Abscess." BioMed Research International 2022: 3650213.
	Background. Pelvic abscess surgery consists mostly of open laparotomy and laparoscopic surgery. Open surgery is regarded as a classic procedure. With the rise and promotion of laparoscopic indications in recent years, comparative studies of the two's postoperative effectiveness have been limited. Objective. To compare the clinical effects of laparoscopic exploratory surgery and open surgery in the treatment of pelvic abscess. Methods. Through computer searches of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases, we found publicly available case-control research on laparoscopic surgery and open surgery for treating pelvic abscess. The papers that met the evaluation criteria were screened, and meta-analysis was used to look at 8 papers on laparoscopic surgery and open surgery for treating pelvic abscess from 2010 to 2021. Results. The results of this study showed that compared with the open laparotomy group, the incidence of laparoscopic group in the incision infection rate (RR=0.29, 95% CI (0.20, 0.41), and P<0.00001), the incidence of intestinal injury (RR=0.08, 95% CI (0.04, 0.14), and P<0.00001), incidence of intestinal obstruction (RR=0.26, 95% CI (0.08, 0.90), and P=0.03<0.05), and postoperative pelvic abscess recurrence rate (RR=0.34, 95% CI (0.13, 0.86), and P=0.02<0.05) are lower than open surgery, and the difference of these four items is statistically significant. There was no difference in the risk of urinary tract injury between laparoscopic surgery and open surgery (RR=0.92, 95% CI (0.27, 3.17), and P=0.89>0.05). Conclusion. In terms of incision infection, intestinal damage, intestinal obstruction, and recurrence of pelvic abscess, the laparoscopic group clearly outperforms the open group, and it merits clinical promotion and use.Copyright © 2022 Xiaolu Chen et al.

Chen, X., et al. (2022). "Meta-analysis of therapeutic efficacy and effects of integrated traditional Chinese and Western medicine on coagulation and fibrinolysis system in patients with threatened abortion and polycystic ovary syndrome." American journal of translational research 14(5): 2768-2778.
	Background: Polycystic ovary syndrome (PCOS) patients are prone to early pregnancy loss. Studies have found that the blood fibrinolytic activity of PCOS patients is closely related to the high abortion rate. At present, it is considered that the combination of traditional Chinese and Western medicine in the treatment of PCOS with threatened abortion has a good effect on fetal protection. Therefore, the clinical efficacy of the combination of traditional Chinese and Western medicine in the treatment of PCOS with threatened abortion was systematically evaluated, and the effect of traditional Chinese medicine on the blood fibrinolytic status of patients was also evaluated.; Methods: The clinical randomized controlled trials (RCTs) of integrated traditional Chinese and Western medicine in the treatment of PCOS with threatened abortion were reviewed from four Chinese databases (CNKI, WANFANG, VIP, and SINOMED) and two English databases (PubMed, EMBASE) from their time of establishment to May 2021. According to the inclusive and exclusive criteria, tests were selected, data were extracted and evaluated, the systematic review was carried out by description analysis, and the meta-analysis was conducted using RevMan 5.3 software from Cochrane Collaboration. Begg's and Egger's tests were performed for assessing symmetries of funnel plot by the software Stata 16.0.; Results: 6 RCTs involving 361 participants were included. Meta-analysis results showed that integrated traditional Chinese and Western medicine can increase the total efficacy compared with the control groups [RR=1.22, 95% CI (1.10, 1.35), P=0.0002]. Meanwhile, the improvement of TCM syndrome integral [MD=-2.11, 95% CI (-2.56, -1.66), P<0.00001], D-II [MD=-0.29, 95% CI (-0.49, -0.09), P=0.004], Hcy [MD=-3.02, 95% CI (-3.64, -2.39, P=0.00001], PAI-I [SMD=-2.38, 95% CI (-2.82, -1.73), P<0.00001] were better than a single Western medicine treatment. And it can increase the level of β-HCG [SMD=3.44, 95% CI (1.87, 5.01), P<0.0001], P [MD=7.70, 95% CI (7.10, 8.31), P<0.00001], E2 [MD=205.36, 95% CI (140.93, 269.80), P<0.00001]. The funnel plot, Egger's test (P=0.210), and Begge's test (P=0.573) suggested that there was no evidence of substantial publication bias.; Conclusions: The effect of integrated traditional Chinese and Western medicine is better than that of Western medicine alone in the treatment of PCOS with threatened abortion, and it has certain advantages in improving the fibrinolytic status of patients. However, due to the limitation of the quality and quantity of the included literature, more rigorous and larger sample studies are needed to confirm these conclusions in the future.; Competing Interests: None. (AJTR Copyright © 2022.)

Chen, X.-T., et al. (2023). "Does endometrial compaction before embryo transfer affect pregnancy outcomes? a systematic review and meta-analysis." Frontiers in Endocrinology 14: 1264608.
	Objective: There is no clear evidence of clinical significance of endometrial compaction, which can be measured by a reduction in endometrial thickness (EMT) during the follicular-luteal transition before the day of embryo transfer. In this study, we aim to determine whether endometrial compaction has an effect on in vitro fertilization (IVF) success.; Methods: We searched PubMed, Cochrane, Embase, and Web of Science electronic databases for studies published in English up to March 2023. Heterogeneity between studies was assessed using the I 2 statistic. The random effects model and fixed effects model was used to pool the risk ratio (RR) with a corresponding 95% confidence interval (CI). A subgroup analysis was performed based on different methods of ultrasonic measurement and different endometrial compaction rates (ECR). Stata 17.0 software was used for meta-analysis. Pregnancy outcomes, which included clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and spontaneous abortion rate, were evaluated.; Results: In this study, 18 cohort studies were included, involving 16,164 embryo transfer cycles. Pooled results indicated that there was no significant difference between the endometrial compaction group and the non-compaction group in terms of clinical pregnancy rate (RR [95% CI]=0.98 [0.90,1.08]; I 2 = 69.76%), ongoing pregnancy rate (RR [95% CI]=1.18 [0.95,1.47]; I 2 = 78.77%), live birth rate (RR [95% CI]= 0.97 [0.92,1.02]; I 2 = 0.00%) or spontaneous abortion rate (RR [95% CI]= 1.07[0.97,1.26]; I 2 = 0.00%). According to the subgroup analysis of ultrasonic measurement methods, in the transvaginal ultrasound (TVUS) combined with abdominal ultrasonography (AUS) cycles of the endometrial compaction group, the rate of ongoing pregnancy (RR [95% CI] = 1.69 [1.26, 2.26]; I 2 = 29.27%) and live birth (RR [95% CI] = 1.27 [1.00,1.61]; I 2 = 62.28%) was significantly higher than that of the non-compaction group. Additionally, subgroup analysis based on ECR revealed a significantly higher rate of ongoing pregnancy when ECR ≥ 15% (RR [95% CI] = 1.99 [1.61, 2.47]; I 2 = 0.00%).; Conclusion: Endometrial compaction has no adverse effect on clinical pregnancy rate, ongoing pregnancy rate, live birth rate, or spontaneous abortion rate. A possible explanation for the contradictory findings of previous studies lies in the method by which the EMT is measured.; Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42023430511, identifier CRD42023430511.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Chen, Sun and Song.)

Chen, Y., et al. (2022). "Association between statin use and the risk, prognosis of gynecologic cancer: A meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 268: 74-81.
	Background: Recent evidence has demonstrated that the salutary effect of statins on the prevention and prognosis of cancers, including gynecologic cancers. However, due to the heterogeneity of tumors, the results from related studies regarding the association between statin therapy and gynecologic cancers are conflicting. Thus, we conducted this meta-analysis to better understand the relationship between statins use and gynecologic cancers.; Methods: We searched for articles published before July 2021 in the databases: PubMed, Web of Science, Medline, EMBASE and Google Scholar. We computed odds ratio (OR)/relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CI) regarding the association between statin use and the risk or prognosis of gynecologic cancers by using STATA 12.0 software.; Results: The present meta-analysis showed that statin use was associated with a lower risk of gynecologic cancer (OR/RR = 0.89, 95% CI 0.83 to 0.96, I 2 = 60.6%, p < 0.001). Statin use was associated with lower risks of endometrial cancer and ovarian cancer (endometrial cancer: OR/RR = 0.81, 95% CI 0.70 to 0.94, I 2 = 62.3%, p = 0.001; ovarian cancer: OR/RR = 0.92, 95% CI 0.85 to 1.00, I 2 = 42.1%, p = 0.077). The present meta-analysis showed that statin use was associated with a lower mortality of gynecologic cancer (HR = 0.73, 95% CI 0.67 to 0.80, I 2 = 39.0%, p = 0.03). Statin use was associated with lower mortalities of endometrial cancer and ovarian cancer (endometrial cancer: HR = 0.71, 95% CI 0.64 to 0.80, I 2 = 31.9%, p = 0.144; ovarian cancer: HR = 0.78, 95% CI 0.73 to 0.83, I 2 = 43.9%, p = 0.051).; Conclusion: Statins use was inversely associated with the risk and mortality of gynecologic cancers. Meanwhile, we need more well-designed and high-quality studies with strong evidence for definite conclusions that determine clinical practice.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021. Published by Elsevier B.V.)

Chen, Y., et al. (2023). "Systematic review and meta-analysis of reproductive outcomes after high-intensity focused ultrasound (HIFU) treatment of adenomyosis." Best practice & research. Clinical obstetrics & gynaecology 92: 102433.
	High-intensity focused ultrasound (HIFU) has emerged as a promising uterus-sparing and possibly fertility-sparing treatment modality for women with adenomyosis, especially those who desire to conceive. We conducted this systematic review and performed a meta-analysis on clinical studies aimed to improve reproduction in women with adenomyosis. After extensive search of PubMed and CNKI, we identified 10 studies published in English and Chinese involving a total of 557 patients with adenomyosis who desired to conceive after HIFU treatment. We found a pooled estimate of pregnancy rate of 53.4% and of the live birth rate of 35.2%, and there was a substantial heterogeneity among these studies. While there is a potential for HIFU treatment to improve fertility for patients with adenomyosis who desired to conceive, such evidence is very weak as of now. Comparative studies with much higher methodological rigor, preferably randomized clinical trials, are badly needed to further illuminate this issue.

Chen, Y., et al. (2019). "Efficacy of ten interventions for endometriosis: A network meta-analysis." Journal of cellular biochemistry 120(8): 13076-13084.
	Objective: Clinical trials comparing the efficacy of different interventions for endometriosis are limited and controversial. The aim of the present study is to perform a network meta-analysis on the efficacy of various interventions for endometriosis.; Methods: We searched PubMed and Ovid EMBASE through 1 June, 2018, for trials reporting the pain score and 1-year pregnancy rate of patients including at least one pair of direct control group. The mean difference of pain score, odds ratio of 1-year pregnancy rate, and their associated 95% credible intervals (CrI) were used to describe efficacy. The surface under the cumulative ranking curve (SUCRA) was calculated to illustrate the rank probability of various treatments for different outcomes, on the basis of network meta-analysis.; Results: Our meta-analysis enrolled six studies for the evaluation of reducing pain and 10 studies for the 1-year pregnancy rate. All involved trials were sufficiently powered with a low risk of bias. Expectant management (EM), progesterone (PR), and gonadotropin-releasing hormone (GnRH)-agonist (GN) were significantly effective to reduce pain when compared with the placebo; EM ranked the highest on the SUCRA curve. For the 1-year pregnancy rate, no significant difference between the interventions was evident. Ablation ranked the highest with a SUCRA value of 0.6328. The rank of EM was acceptable with a SUCRA value of 0.4452. Our experimental results need to be verified by more high-quality randomized controlled trial articles.; Conclusion: Limited available evidence showed that EM, PR, and GN were significantly effective to reduce pain when compared with the placebo. Due to a lack of convincing evidence favoring surgery or medication, we recommend considering EM. (© 2019 Wiley Periodicals, Inc.)

Chen, Y., et al. (2020). "Fuke Qianjin Combined with Antibiotic Therapy for Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2020: 5372839.
	Background: Pelvic inflammatory disease (PID) without timely and proper treatment can cause long-term sequelae; meanwhile, patients will be confronted with the antimicrobial resistance and side effects. Chinese patent medicine as a supplement is used to treat PID with satisfactory clinical efficacy. This study evaluated the efficacy and safety of Fuke Qianjin (FKQJ) combined with antibiotics in the treatment of PID.; Methods: Eight electronic databases and other resources were searched to make a collection of the randomized controlled trials (RCTs) from 1990 to 2019. The RCTs contrasting the effect of FKQJ combined with antibiotics regimens and antibiotics alone in reproductive women with PID were included. The antibiotics regimens are all recommended by the guidelines. Two reviewers independently screened the studies, extracted the data, and assessed the methodological quality of the included studies. Then, the meta-analyses were performed by RevMan 5. 3 software if appropriate.; Results: Twenty-three RCTs (2527 women) were included in this review. The evidence showed that FKQJ combined with antibiotics improved the markedly effective rate compared to antibiotics alone group (RR = 1.38, 95% CI 1.27 to 1.49, I 2 = 42%), shortened the improvement time of low abdominal pain (MD = -1.11, 95% CI -1.39 to -0.84, I 2 = 38%), and increased the rate of lower abdominal pain improvement (RR = 1.35, 95% CI 1.19 to 1.55, I 2 = 0). The implementation of adjuvant reduced the recurrent rate compared with antibiotics alone (RR = 0.27, 95% CI 0.13 to 0.56, I 2 = 0%).; Conclusions: Based on available evidence, FKQJ combined with antibiotics therapy have certain outcomes on increasing the markedly effective rate, decreasing the recurrent rate compared with antibiotics alone group. This therapy appears to improve lower abdominal pain and curtail the relief time. Due to the low quality and the risk of bias, any high-quality evidence or longer follow-up period should be advisable and necessary in the future.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2020 Yu Chen et al.)

Chen, Z., et al. (2022). "The effect of mindfulness-based stress reduction therapy on maternal anxiety, depression, and sleep quality: A protocol for systematic review and meta-analysis." Medicine (United States) 101(8): 28849.
	Background:Depression and anxiety are common in the prenatal and postnatal periods, which significantly influence pregnant women and their unborn babies. Pharmacological interventions can negatively affect maternal and infant health outcomes, while psychotherapy can avoid adverse events of medication and improve maternal depression and anxiety. Whether mindfulness-based stress reduction (MBSR) can alleviate maternal anxiety and depression and improve sleep quality is still controversial. Therefore, we aim to conduct a meta-analysis by collecting randomized controlled trials (RCTs) reporting the effects of MBSR on maternal anxiety, depression, and sleep quality, thus providing evidence-based medical evidence for non-pharmacological interventions. Method(s):RCTs reporting the effect of MBSR on maternal anxiety, depression, and sleep quality versus conventional obstetric care will be searched in online databases, including the Cochrane Central Register of Controlled Trials Repositories, PubMed, Embase, Web of Science, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Database. Literature selection, data extraction, risk of bias assessment, and meta-analyses will be independently completed by 2 researchers. Meta-analysis will be performed by using RevMan5.4. Result(s):The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion(s):This study will provide reliable evidence-based evidences for the effects of MBSR on improving maternal anxiety, depression, and sleep quality.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Chen, Z., et al. (2021). "Effect of antibiotics on urine leakage in women with refractory detrusor overactivity: a phase IIb randomized trial." Neurourology and Urodynamics 40(1): 158‐167.
	Aim: Because bacterial cystitis is common in women with refractory detrusor overactivity, the aim was to compare the efficacy of 6 weeks of rotating antibiotics versus placebo, in conjunction with an anticholinergic, in controlling the symptoms of urge incontinence. Methods: In a multicenter phase IIb double‐blinded randomized placebo‐controlled trial, women with urodynamically proven refractory detrusor overactivity were randomized in a 2:1 ratio of antibiotics versus placebo for 6 weeks, in addition to darifenacin for 6 months. Any woman with disabling cystitis symptoms was given appropriate antibiotics (“clinical override”). The primary outcome was the degree of urge incontinence change at 6 weeks and 6 months on 24‐h pad test. Secondary outcomes were changes in leaks and voids per day measured on 3‐day bladder diary and quality of life measures. Microbiological data were collected at all visits. Results: Although 278 women were screened, only 36 were randomized and 33 (91.7%) completed the trial. Leakage on 24‐h pad test decreased at 6 months by 75 g in patients receiving antibiotics versus 35 g in placebo. Cure of urge incontinence occurred at 6 months in 10/21 (48%) of antibiotics versus 2/12 (17%) of placebo. Clinical override, necessitating treatment of cystitis, occurred in 41.6% of placebo versus 16.7% of the antibiotic group by 6 months. Conclusion: Despite the small sample size, the study showed a significant reduction in pad leakage and leaks per day over 24 h in the active treatment group over a 6‐month period. Nearly half of patients on placebo had disabling urinary tract infection symptoms that required clinical override treatment.

Chen, Z., et al. (2022). "Effectiveness and Safety of the Traditional Chinese Medicine Treatment ( HuoxueHuayu Therapy) for Malignant Tumors: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2022: 7944063.
	Background: A malignant tumor is one of the refractory diseases that threaten human life and health. HuoxueHuayu therapy (one of the Traditional Chinese Medicine therapies to promote blood circulation and remove blood stasis) is widely used as an antitumor supplementary method. However, its efficacy and safety are still controversial. Therefore, the objective of this study was to provide evidence-based evidence for HuoxueHuayu therapy in the treatment of malignant tumors and confirm its safety and effectiveness.; Methods: A systematic search in 8 electronic databases targeted randomized clinical studies evaluating HuoxueHuayu therapy for response evaluation, tumor progression rate, quality of life (QoL), peripheral hemogram, performance status, immunologic function, tumor marker, and blood coagulation function in cancer patients, published from the establishment of the database to December 31, 2020. Risk ratio (RR) was used for counting data, mean difference (MD) or standardized mean difference (SMD) was used for measurement data, and 95% confidence interval (CI) was used as efficacy analysis statistics.; Results: Our search identified 69 studies, evaluating 4402 patients in total. Randomized controlled trials (RCTs) evaluated gastric ( n = 14), lung ( n = 18), pancreatic ( n = 2), colorectal ( n = 10), liver ( n = 14), breast ( n = 2), ovarian ( n = 2), gallbladder ( n = 1), esophagus ( n = 1), and combined ( n = 14) cancers and hematological malignancies ( n = 2). The duration of HuoxueHuayu therapy ranged from 3 to 48 weeks. Methodological bias was low in 64 studies and high in 5 studies. HuoxueHuayu therapy was associated with significant improvement in response evaluation (Response Evaluation Criteria in Solid Tumor (RECIST): RR: 1.44, 95% CI: 1.27 to 1.63, I 2 = 0%, n = 33 studies; World Health Organization Criteria in Solid Tumors (WHOCIST): RR: 1.40, 95% CI: 1.23 to 1.59, I 2 = 0%, n = 26 studies), recurrence rate (RR: 0.85, 95% CI: 0.72 to 0.99, I 2 = 0%, n = 2 studies), quality of life, performance status (MD: 5.60, 95% CI: 5.04 to 6.15, p < 0.001), immunologic function (CD3: SMD: 1.23, 95% CI: 0.79 to 1.66, p < 0.001; CD4: SMD: 1.25, 95% CI: 0.77 to 1.74, p < 0.001; CD4/CD8: SMD: 1.05, 95% CI: 0.69 to 1.42, p < 0.001; natural killer cell (NK): SMD: 0.74, 95% CI: 0.32 to 1.15, p < 0.001), tumor marker, and blood coagulation function (D-dimer (D-D); fibrinogen (FIB)). In addition, HuoxueHuayu therapy could reduce toxicity caused by chemotherapy and radiotherapy without risks of liver and kidney injury or bleeding, although the effect on tumor metastasis was uncertain.; Conclusions: The present update of our systematic review and meta-analyses provided essential evidence for the beneficial effect of HuoxueHuayu therapy to show promise in cancer treatment, improving quality of life, addressing cancer-related symptoms, and reducing toxicity in a secure way.; Competing Interests: The authors declare that they have no conflicts of interest in this paper. (Copyright © 2022 Zehui Chen et al.)

Cheng, H., et al. (2019). "Oncological Outcomes and Safety of Ovarian Preservation for Early Stage Adenocarcinoma of Cervix: A Systematic Review and Meta-Analysis." Frontiers in Oncology 9: 777.
	Objectives: To evaluate the oncological outcomes and safety of ovarian preservation, and to review the prognostic factors for ovarian metastases in early stage cervical adenocarcinoma. Methods: PubMed, Embase, and Cochrane databases were searched for publications up to January 2019. Two investigators independently screened the studies for eligibility and extracted specific data. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using STATA statistical software version 19.0. Results: A total of 68 unique manuscripts were identified through the search strategy, and 10 studies were included in the meta-analysis of the safety of ovarian preservation. Fixed-effects model was used because of moderate heterogeneity. Pooled results of the included studies showed that ovarian preservation is not associated with a statistically significant OS (OR 1.00, 95% CI 0.64-1.56, I 2 = 25.7%) or PFS (OR 0.98, 95% CI 0.57-1.66, I 2 = 0%) in early stage cervical adenocarcinoma. In addition, 19 studies were included in the review of prognostic factors for cervical adenocarcinoma and risk factors for ovarian metastases. The incidence of ovarian metastases was 0% in stage IA, 2.8% in stage IB, 3.4% in stage IIA, and 11.8% in stage IIB cervical adenocarcinoma. International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, deep stromal invasion (DSI), lymph node metastasis (LNM), and vaginal invasion were significantly related to poor prognosis. Risk factors associated with ovarian metastases included age, FIGO stage, tumor size, DSI, parametrial invasion, corpus uteri invasion, LNM, vaginal invasion, and blood vessel invasion. Conclusions: Ovarian preservation in young patients with early stage cervical adenocarcinoma is safe and has no significant effect on OS or PFS. Preserving ovaries in patients with FIGO stage IIB seems not reasonable because of the high rate of ovarian metastasis.

Cheng, M., et al. (2020). "Efficacy of Applying Hyaluronic Acid Gels in the Primary Prevention of Intrauterine Adhesion after Hysteroscopic Myomectomy: A Meta-Analysis of Randomized Controlled Trials." Life (Basel, Switzerland) 10(11).
	Intrauterine adhesion (IUA), which mainly occurs after intrauterine surgery or an inflammatory process, is an important but often neglected condition in women of reproductive age. The presentation of IUA varies greatly, ranging from symptom-free to severe, with amenorrhea or infertility. With much advanced development of intrauterine instruments, more intrauterine diseases can be successfully cured by hysteroscopic surgery. Among these, submucosal myoma is one of the best examples. Submucosal myomas are often related to abnormal bleeding, anemia, and possible infertility or miscarriage. However, submucosal myoma after hysteroscopic myomectomy may be complicated by IUA in various grades of severity, and its incidence and prevalence might be nearly one-quarter to one-third of patients, suggesting an urgent need for efforts to decrease the risk of developing IUA after hysteroscopic myomectomy. Many strategies have been reported to be useful for this purpose, and intrauterine application of anti-adhesive gels, such as polyethylene oxide-sodium carboxymethylcellulose (PEO-NaCMC) or auto-crosslinked hyaluronic acid (ACHA), has become increasingly popular in routine clinical practice. This meta-analysis is aimed at investigating the effect of ACHA on the primary prevention of IUA formation after hysteroscopic myomectomy. A pooled analysis of three studies (hysteroscopic surgeries for fibroids, polyps, and septum) including 242 women showed that using PEO-NaCMC or ACHA gel decreased the IUA rate with an odds ratio (OR) of 0.364 (95% confidence interval (CI) 0.189-0.703, p = 0.03). Pooled analysis of two studies that limited the use of ACHA in 119 women showed that the application of ACHA gel for the primary prevention of IUA in patients after hysteroscopic myomectomy led to a statistically significant reduction of the development of IUA postoperatively (OR 0.285, 95% CI 0.116-0.701, p = 0.006). All of this suggests that the use of ACHA gel in patients after hysteroscopic myomectomy could significantly reduce de novo IUA, although more evidence is needed.

Cheng, P., et al. (2020). "The acupuncture-related therapy for post-stroke urinary incontinence: A protocol for systematic review and network meta-analysis." Medicine (United States) 99(44): E22865.
	Background:With the rising incidences stroke, the Post-Stroke Urinary Incontinence (PSUI) has become one of the common clinical sequelae. PSUI not only lowers the quality of life of patients, but also impacts tremendously to mental health. As a treasure of Chinese medicine, acupuncture and its related therapies have been widely accepted in clinical treatment of PSUI. Recently, there have been many clinical studies on the treatment of PSUI with acupuncture and related therapies, but the best way to treat PSUI is controversial. Therefore, the purpose of this paper is to provide an optimal ranking regarding acupuncture and its related therapies for PSUI. Method(s):The five domestic and foreign databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database will be systematically searched. The time range of the literature search is from the date of establishment to August 31, 2020. The main evaluation outcome was the number of patients after treatment, and the frequency of urinary incontinence. The secondary evaluation outcome was International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Barthel Activities of Daily Living Index (Barthel ADL Index) and the incidence rate of adverse events. The methodological quality of the article will evaluated by Cochrane Collaboration's Tool and the quality of evidence will evaluated through Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. The Network Meta-Analysis (NMA) will be completed using Stata statistical software. Result(s):The final results of this study will be published in a peer-reviewed journal. Conclusion(s):This network meta-analysis will compare the efficacy and safety of different acupuncture therapies in the treatment of PSUI and summarize the best treatment options, which will help patients and doctors to choose effective acupuncture methods in time.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Cheng, P., et al. (2021). "Role of Arts Therapy in Patients with Breast and Gynecological Cancers: A Systematic Review and Meta-Analysis." Journal of Palliative Medicine 24(3): 443-452.
	Background: Women with breast and gynecological cancers often experience adverse symptoms such as anxiety, depression, pain, and fatigue. Objective(s): The purpose of this meta-analysis was to clarify the role of arts therapy (based on music, painting, and dance) in quality of life and reported symptoms among women with breast and gynecological cancers. Method(s): Articles on arts therapy were retrieved from relevant electronic databases through to May 2020. The outcomes (quality of life and symptoms such as anxiety, depression, pain, and fatigue) were estimated according to standard or validated scales that assessed psychological status and activities of daily living. The effect sizes for arts therapy were combined to show the standardized mean difference (SMD) and corresponding confidence interval (CI), and a random-effects model was used for computation. Result(s): In total, 19 randomized controlled studies were included in this meta-analysis. The pooled SMDs for arts therapy were statistically significant for quality of life (0.58; 95% CI: 0.02-1.13; p = 0.04), anxiety (-1.10; 95% CI: -1.88 to -0.32), depression (-0.71; 95% CI: -1.19 to -0.23), pain (-1.01; 95% CI; -1.97 to -0.08), and fatigue (-0.59; 95% CI: -1.18 to -0.00). However, the summary SMDs for arts therapy was not significant for sleep disturbance, anger, vigor, tension, confusion, and stress. Conclusion(s): This meta-analysis shows that arts therapy has favorable effects on improving quality of life and depression among patients with breast and gynecological cancers. Arts therapy also has positive effects on improving anxiety, pain, and fatigue symptoms among patients with breast cancer. Further studies are required to confirm the effect of arts therapy on anxiety, pain, and fatigue in patients with gynecological cancer.© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.

Cheng, P. and X. H. Yang (2022). "Preservation of the fallopian tube in ectopic tubal pregnancy. An analysis of the outcome of two laparoscopic surgical approaches." Annali italiani di chirurgia 93: 241-247.
	INTRODUCTION: The application of laparoscopic partial tubal resection with end-to-end anastomosis can reduce the incidence of persistent ectopic pregnancy. AIM: We aim to compare the therapeutic effects of laparoscopic fenestration and laparoscopic partial tubal resection with end-to-end anastomosis in the treatment of tubal ectopic pregnancy. MATERIAL AND METHODS: The patients were randomly divided into the observation group (the group treated with laparoscopic partial tubal resection with end-to-end anastomosis, n=238) and the control group (the group treated with laparoscopic fenestration, n=213). The average operation time, intraoperative blood loss, postoperative exhaust time and hospital stay were observed to evaluate the clinical effect. In addition, the time required for the beta-HCG to drop to normal level, the patency of the fallopian tubes and the ovarian function were observed in the two groups after the operation. RESULT(S): There was no significant difference between observation group operation time, intraoperative hemorrhagic amount, blood beta-HCG recovery time and hospital time and control group (P > 0.05). The postoperative fallopian tube patency rate in the observation group was 67.58%, significantly higher than the control group (P < 0.05). In addition, there was no significant difference in ovarian function between the two groups. CONCLUSION(S): The method of laparoscopic partial tubal resection with end-to-end anastomosis is more effective in the treatment of tubal ectopic pregnancy, and has less impact on ovarian function, which can effectively improve the probability of normal pregnancy after the operation. KEY WORD: Fallopian tube, Ectopic pregnancy, Laparoscopic fenestration, Laparoscopic partial tubal resection with end-to-end anastomosis.

Cheng, Q., et al. (2022). "Effectiveness of psychoeducational interventions among caregivers of patients with cancer: A systematic review and meta-analysis." International journal of nursing studies 127: 104162.
	BACKGROUND: Many of the needs of caregivers of patients with cancer are unmet, particularly their informational and psychological needs. Psychoeducational interventions that focus on providing caregivers with information, and on meeting their emotional and psychosocial needs, may therefore be effective. OBJECTIVE: To evaluate the effectiveness of psychoeducational interventions on the outcomes of caregivers of patients with cancer and identify characteristics of effective psychoeducational interventions. DESIGN: A systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The databases of PubMed, Embase, the Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature Complete, the British Nursing Index, PsycINFO, Ovid Emcare, Scopus, Chinese Journal Net, and Wan Fang Data were searched in December 2020. Clinical trial registers, related websites and reference lists of included studies were also examined. REVIEW METHODS: The Cochrane Risk of Bias Tool was used to appraise the quality of included studies. Meta-analysis was conducted, and narrative syntheses were performed where meta-analysis was inappropriate. RESULTS: Fourteen articles describing 12 studies were included. The results of the meta-analysis showed that psychoeducational interventions have short-term (immediately post-intervention) positive effects on relieving anxiety [SMD: -0.50, 95%CI: (-0.97, -0.02), p = 0.04], depression [SMD: -0.54, 95%CI: (-0.76, -0.32), p < 0.00001] and caregiver burden [SMD: -0.57, 95%CI: (-0.87, -0.27), p = 0.0002] and improving their quality of life [SMD: 0.42, 95%CI: (0.23, 0.62), p < 0.0001) and self-efficacy [SMD: 0.31, 95%CI: (0.09, 0.53), p = 0.006] in the caregivers of patients with cancer. They also showed long-term (at least 3 months post-intervention) positive effects on improving physical health [SMD: 0.26, 95%CI: (0.05, 0.47), p = 0.02]. The types of psychoeducational interventions varied in the 12 studies. However, the main contents of effective psychoeducational interventions included tasks related to health care provisions for patients, caregiver self-care and stress management, and relationship and coping skills. In general, most studies had short follow-up periods and involved caregivers of older patients with cancer (>40 years old). CONCLUSIONS: Psychoeducational interventions may have short-term desirable effects on caregivers' anxiety, depression, quality of life, burden and self-efficacy and long-term desirable effects on physical health. Individual psychoeducational intervention varied in contents, delivery mode, dosage and format. Research is needed to further specify the optimal combination of contents. Further high-quality RCTs are warranted, with longer follow-up periods, for caregivers of patients with cancer, especially caregivers of younger patients with cancer.

Cheng, X., et al. (2022). "Does antibiotic therapy for chronic endometritis improve clinical outcomes of patients with recurrent implantation failure in subsequent IVF cycles? A systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics 39(8): 1797-1813.
	Purpose: This study aims to assess whether antibiotic therapy for chronic endometritis (CE) could improve subsequent IVF outcomes in patients with recurrent implantation failure (RIF).; Methods: Studies that explore CE treatment in patients with RIF were retrieved from PubMed, EMBASE, Wanfang, and Google Scholar up to Jan 31, 2022. All retrieved studies were selected according to the inclusion and exclusion criteria. The main outcome measures include implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR/LBR), and miscarriage rate (MR). Odds ratios (ORs) were analyzed for pregnancy outcomes with a 95% confidence interval (CI).; Results: Nine articles were enrolled in this study. Patients receiving oral antibiotic administration (OAA) did not show any advantage over patients without CE with regard to IR, OPR/LBR, and MR, but they showed a higher CPR. Patients with cured CE after OAA therapy had significantly higher CPR, IR, and OPR/LBR compared with patients without CE. Patients with persistent CE after OAA therapy had significantly lower IR, CPR, and OPR/LBR compared with patients without CE. Patients with cured CE had significantly higher IR, CPR, and OPR/LBR compared with persistent CE patients.; Conclusions: Antibiotic treatment may improve the pregnancy outcomes of RIF patients in subsequent IVF cycles only if the condition of CE is confirmed cured in a control biopsy afterwards. Otherwise, no sufficient evidence has shown improvements in clinical outcomes in RIF patients with persistent CE. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cheng-Chun, Y. and L. Jyun-Yan (2021). "Prophylactic intraoperative uterine artery embolization during cesarean section or cesarean hysterectomy for patients with abnormal placentation."
	
Chengyang, J., et al. (2021). "Pelvic floor muscle training for women with urinary incontinence after stroke: a systematic review."
	
Chen-Li, D., et al. (2022). "Ketamine as potential treatment for postpartum depression: A narrative review." Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists 34(4): 264-274.
	Background: Postpartum depression (PPD) is a severe, debilitating mood disorder with consequences for both mothers and children, highlighting the need for rapid-acting and effective treatments for PPD. The aim of this narrative review is to synthesize the available literature on the administration of ketamine for PPD and propose ketamine as a viable and advantageous treatment.; Methods: A search was conducted on MEDLINE/PubMed, PsycInfo, and Embase databases from inception to October 10, 2021 for preclinical studies, interventional studies (ie, open-label and randomized controlled trials), as well as systematic reviews and meta-analyses evaluating the use of ketamine in postpartum populations. Completed and ongoing clinical trials were identified on ClinicalTrials.gov.; Results: Four clinical trials were identified. Results from this review support additional investigation into ketamine as a potential treatment for PPD.; Conclusions: Ketamine may be a favorable option for treating PPD due to its antidepressive and analgesic effects, short infusion time, and rapid clearance from the maternal bloodstream. However, there is insufficient evidence to support its use in this population, underscoring the importance of additional clinical research investigating ketamine for PPD.

Chermansky, C. J., et al. (2022). "Intravesical Instillation of OnabotulinumtoxinA in the Treatment of Refractory Overactive Bladder in Participants with Urinary Incontinence." Journal of urology 208(4): 855-862.
	Purpose:Intradetrusor injections of onabotulinumtoxinA are efficacious for the treatment of overactive bladder with urgency urinary incontinence in adults refractory to or intolerant of anticholinergics. Delivery of onabotulinumtoxinA via instillation would reduce the need for intradetrusor injections. The objective of this trial was to assess the efficacy and safety of intravesical instillation of an onabotulinumtoxinA + hydrogel admixture.Materials and Methods:After review of a stage 1 safety phase by an independent committee, participants were recruited into stage 2 and randomized to either onabotulinumtoxinA 100, 300, 400, or 500 U, or placebo, all with hydrogel admixture. End points included change from baseline to week 12 in the number of urinary incontinence episodes (primary); micturition, urgency urinary, and nocturia episodes/day; volume voided per micturition; proportion of participants with a >=50% decrease from baseline in urinary incontinence episodes/day; and Overactive Bladder Questionnaire total score. Adverse events were reported. Result(s):Change from baseline to week 12 in number of urinary incontinence episodes was -2.72 with placebo and ranged from -0.89 to -1.85 in the onabotulinumtoxinA + hydrogel treatment groups. No difference from placebo was observed for any efficacy end point. The proportions of participants with treatment-emergent adverse events were similar among all groups, with asymptomatic bacteriuria the highest reported (6.7%-15.5%). There were no reports of urinary retention or elevated post-void residual volume. Conclusion(s):Intravesical instillation of an onabotulinumtoxinA + hydrogel admixture for the treatment of refractory overactive bladder was well tolerated, but it showed no improvement over placebo.Copyright © 2022 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.

Chernukha, G. E., et al. (2022). "NEW PERSPECTIVES ON OVULATION INDUCTION WITH LETROZOLE IN WOMEN WITH POLYCYSTIC OVARY SYNDROME." Akusherstvo i Ginekologiya (Russian Federation) 2022(12): 107-114.
	Objective: To compare the efficacy and adverse event rates of letrozole in a stair-step and standard ovulation induction (01) protocols in women with polycystic ovary syndrome (PCOS) and anovulatory infertility. Material(s) and Method(s): The study included 194 patients aged 28.7 (25;33), body mass index 21.5 (21;26) kg/m2. Of them, 106/194 (54.6%) women did not respond to the initial stimulation with 2.5 mg letrozole. They were divided into group 1 (n=52) and group 2 (n=54) undergoing stair-step protocol and standard protocol, respectively. During 01, the patients underwent ultrasound monitoring of ovarian and endometrial status. Furthermore, the clinical evaluation included estimated time of ovulation and ovulation and pregnancy rates. Result(s): The ovulation rates were equally high in both groups and was 92.3% on the stair-step protocol and 85.2% on the standard protocol (p=0.25). The time to ovulation was statistically significantly shorter in the stair-step protocol [33.9 (3.23) versus 59.5 (11.96) days; p<0.001J. The mean M echo was larger in the same group [0.2 (2.2) mm versus 9.3 (2.2) mm; p=0.01[. There was no statistical difference in pregnancy and live birth rates between the stair-step and standard protocols [17/52 (32.7%) versus 12/54 (22.2%); p=0.23 and 15/52(28.8%) versus 11/54 (20.4%);p=0.31[. None of the patients developed ovarian hyperstimulation syndrome (OHSS). The incidence of multiple pregnancies in group 1 was 1/17(5.9%) (p=0.31). Conclusion(s): The stair-step protocol with letrozole allows repeated stimulation without inducing a menstrual-like response and can be considered an effective treatment of anovulatory infertility in PCOS. It reduces the time to ovulation approximately twofold without increasing the risk of OHSS and multiple pregnancies, thus improving patients' quality of life.Copyright © A group of authors, 2022.

Chernyavskaya, M. A. and I. A. Narkevich (2020). "Biological effects of phytoestrogens: Clinical effectiveness and potential application in the treatment of climacteric syndrome." Farmakoekonomika 13(2): 164-169.
	Aim. To review scientific publications on clinical effectiveness and potential application of phytoestrogens (PE) in the treatment of climacteric syndrome. Materials and methods. The PRISMA approach was used. The systematic search was performed in three electronic scientific databases: Cochrane library, PubMed/MEDLINE, and eLIBRARY.ru. The publications were also manually searched for in the reference lists of the relevant articles. Results. The filters were used to select 79 publications; 26 of them were included in the final review. The main method of treatment for the manifestations of the climacteric syndrome is menopausal hormonal therapy (MHT). One of the alternative methods for the control of its symptoms is the application of phytoestrogens (PE), primarily, isoflavones, lignans, and coumestans. Active metabolites of PE are expressed under the influence of gut microflora that is different in various groups of women, which can determine the differences in the effectiveness. Taking into account multidirectional character of the studies as well as numerous publications of low quality, it is still impossible to come to the final conclusion on the effectiveness of PE-containing food supplements (FS) when it comes to a decrease in the occurrence rate and expression of such symptoms as hot flushes, night sweats, and cognitive deterioration. The conclusions on the prevention of cardio-vascular diseases are not definite either. Conclusions. The review showed that scientists could not come to the conclusion on the effectiveness and safety of PE-containing FS. Probably, the most prospective means of the control of climacteric syndrome are FS that contain isoflavones of red clover and soy in the maximum effective concentration. Considering free access to such FS on the market, they must meet high safety requirements.Copyright © 2020, Farmakoekonomika. All rights reserved.

Chi, C. (2022). "Comparison of application of remifentanil and propofol combined anesthesia in painless induced abortion under the monitoring of different anesthesia depth index." Medical Theory and Practice / 医学理论与实践 35(2): 281‐283.
	Objective: To compare the application effect of remifentanil and propofol combined anesthesia in painless induced abortion under the monitoring of different anesthesia depth index (NTI). Methods: A total of 114 patients who underwent painless abortion in our hospital from September 2019 to September 2020 were selected and divided into three groups according to the random number table method. The depth of anesthesia was monitored with Narcotrend. The depth of anesthesia in group A was at the level of D1 (NTI was 47‐56 points), group B was at the level of D2 (NTI was 37‐46 points), and group C was at the level of E0 (NTI was 27‐36 points). The anesthesia effects and adverse reactions were compared, and the levels of serum cortisol and epinephrine were measured and compared before anesthesia and 30 minutes after recovery from anesthesia. Results: The excellent and good rate of anesthesia in group B was significantly higher than that in groups A and C (P<0.05). The recovery time in group B was shorter than that in group C (P<0.05), and the incidence of adverse reactions in group B was lower than that in groups A and C (P<0.05). The levels of serum cortisol and epinephrine in the three groups at 30 min after anesthesia were higher than those before anesthesia (P<0.05), but lower in group B than in groups A and C (P<0.05). Conclusion: When using propofol and remifentanil for compound anesthesia in painless abortion, the depth of anesthesia is optimal at D2 level, which can better meet the needs of surgery, reduce the stress level, speed up the resuscitation process, and have less adverse reactions. few.

Chi, Y., et al. (2022). "Laser treatment vs vaginal estrogen on genitourinary syndrome of menopause in women." PROSPERO International prospective register of systematic reviews.
	
Chiaffarino, F., et al. (2022). "Prevalence of polycystic ovary syndrome in European countries and USA: A systematic review and meta-analysis." European Journal of Obstetrics and Gynecology and Reproductive Biology 279: 159-170.
	We conducted a systematic review and meta-analyses of the prevalence of Polycystic Ovary Syndrome (PCOS) and the frequency of its phenotypes in Europe and the USA, also focusing on temporal trends of the condition, to compare the PCOS prevalence among populations with a similar level of diagnostic resources availability and attitudes toward health problems, to improve comparability of estimates. We considered Europe and USA, two high-income areas with these characteristics. The overall PCOS prevalence according to the NIH1990, ESHRE/ASRM 2003, AES-PCOS diagnostic criteria was respectively 6.2 % (95%CI 5.3-7.0), 19.5 % (95%CI 17.3-21.6), and 15.0 % (95%CI 12.9-17.1), with no appreciable heterogeneity across geographic areas. Phenotype A, the "complete PCOS", showed higher prevalence in all areas (44.8%, 95%CI 40.3-49.3), followed by phenotype D, called "non-hyperandrogenic PCOS" (19.5%), phenotype C termed as "ovulatory PCOS" (16.2%), and phenotype B, presenting as phenotype A but without polycystic ovarian morphology (14.9%). In all the studies analysing temporal trends of PCOS, an increase in prevalence of PCOS was reported, due, at least in part, to changing diagnostic criteria. The prevalence of PCOS is similar in European countries and the USA. Interestingly, some differences in the frequency of PCOS phenotypes emerged between the two areas with a higher frequency of phenotype A and a lower one of phenotype C in the USA. Recognizing the factors which explain these differences would lead to a better understanding of the etiopathogenesis and the clinical expression of PCOS.Copyright © 2022

Chiavarini, M., et al. (2022). "Postmenopausal exogenous hormone therapy and Melanoma risk in women: A systematic review and time-response meta-analysis." Pharmacological research 176: 106054.
	
Chicago University, o. and H. M. S. Gmb (2022). Surgical Myomectomy Followed by Oral Myfembree Versus Standard of Care Trial (SOUL).
	No Results Available Drug: Myfembree Oral Product Fibroid recurrence on ultrasound after myomectomy.|Participants' quality of life assessed by the Quality of Life Questionnaire.|Work Productivity and Activity Impairment assessed by Work Productivity and Activity Impairment Questionnaire.|Female Sexual Function Impairment assessed by Female Sexual Function Index Questionnaire.|Heavy menses recurrence after myomectomy with score ≥ 120 on Pictorial Bleeding Assessment Chart (PBAC).|Pelvic pain recurrence after myomectomy with Numerical Rating Scale (NRS) ≥ 4 at baseline.|The need for surgical/non-surgical reintervention for recurrent symptoms after myomectomy reported by the participant and based on her provider's decision. Female Phase 4 136 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment IRB22-0282 April 2026

Chicago University of Illinois, a. (2023). Time Restricted Eating for the Treatment of PCOS.
	No Results Available Other: 6-h Time restricted eating (TRE)|Other: Calorie restriction (CR)|Other: Control Change in body weight|Change in fat mass, lean mass, visceral fat mass|Change in bone mineral density|Change in waist circumference|Change in Insulin sensitivity|Change in Fasting glucose|Change in Fasting insulin|Change in HbA1c|Change in Blood pressure|Change in heart rate|Change in Plasma lipids (LDL cholesterol, HDL cholesterol, triglycerides)|Change in inflammatory markers (TNF-apha, IL-6, IL-10, IL-B, hs-CRP)|Change in oxidative stress (8-isoprostane)|Change in reproductive hormones (testosterone, DHEA, SHBG, androstenedione)|Change in energy and nutrient intake|Change in physical activity (steps/d)|Change in mood|Change in appetite Female Not Applicable 300 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 2022-1500 January 1, 2028

Chicago University of Illinois, a. and C. Health (2022). Caria: Digital Intervention for Menopause Symptom.
	No Results Available Behavioral: Caria app|Behavioral: Menopause Education Hot Flush Rating Scale|Women's Health Questionnaire Female Not Applicable 150 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2021-0282 December 15, 2022

Chichevatov, D. A., et al. (2023). "TREATMENT OF CERVICAL ESOPHAGEAL CARCINOMA: SYSTEMATIC REVIEW AND META-ANALYSIS." Siberian Journal of Oncology 22(4): 101-108.
	Objectives. Up to date managing a cervical esophageal carcinoma (CEC) has remained a controversial challenge. The choice of treatment is still uncertain. In the present review we attempted to assess eligibility of surgery in treatment of CEC. Material and Methods. We have enquired particular publication databases and the enquiries yielded 24 contributions matching study selection criteria such as (1) original articles published from 2000 to 2022, (2) primary tumor localization in the cervical esophagus, (3) squamous cell carcinoma, (4) available characteristics of studied groups (age, sex, T, N, M, stage), (5) detailed description of curative procedures (radiation therapy, chemotherapy, surgery), (6) information about overall survival. These publications represented two arms of 14 surgical and 17 non-surgical subgroups to analyze. Individual patient dataand parameter estimates have been renewed on the basis of original Kaplan-Meier curves plotted. Results.The analysis revealed a highly heterogeneous (I2=83.76 %; 95 % CI, 71.40-92.16) random effects model. Including a surgical option into treatment of CEC did not affect 3-year overall survival (p=0.665); 46.4 % (95 % CI, 37.4-55.6) vs 43.7 % (95 % CI, 35.3-51.6), respectively. Possibilities of surgical and non-surgical modalitiesemployment were discussed. Conclusion. In treatment of CEC CRT and surgery are non-inferior to each other. These modalities are evenly associated with posterior side effects and complications, which adversely affect functional outcomes and survival. The choice of a treatment mode may depend on tumor response to induction therapy. The latter demands further investigations.Copyright © 2023, Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved.

ChiCtr (2021). "Clinical study of the effects of metformin combined with different dietary intervention patterns on pregnancy and endocrine metabolism in overweight/obese patients with polycystic ovary syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: A group:The first phase of the intervention required lifestyle guidance based on caloric restriction and a low carbohydrate diet accompanied by a 1000mg BID regimen with metformin.Outpatient visits were performed at the 4th, 8th and 12th weeks respectively.;B group:Metformin 1000mg BID was required for a normal structured diet based on caloric restriction.Outpatient visits were performed at the 4th, 8th and 12th weeks respectively.In the second phase of the intervention (12 to 36 weeks), caloric restriction and a normal structured diet with metformin were continued.; CONDITION: E28.200 Polycystic ovary syndrome PRIMARY OUTCOME: pregnancy rate;pregnancy outcome; SECONDARY OUTCOME: weight;Body mess index;waistline;glycometabolism;change in blood fat;change in the function of islets;change in sex hormones;inflammatory indications;change in blood pressure;change in adipokines;change in intestinal flora; INCLUSION CRITERIA: 1. Aged >= 20 years, but <= 40 years; 2. Patients with hyperandrogenemia and meeting the diagnostic criteria for PCOS may be diagnosed with 2 of the following 3 criteria, as amended by the Rotterdam Working Group of the American Society for Reproductive Medicine (ASRM): (1) anovulation or irregular ovulation; (2) evidence of clinical or biochemical changes with elevated androgen levels (such as hirsutis, acne); (3) Ovarian enlargement, at least 12 small follicles with a diameter of 2 9mml on each side and/or unilateral or bilateral ovarian volume >= 10ml.Congenital adrenal hyperplasia and other ovarian tumors secreting testosterone were excluded.3. Body mass index (BMI) >= 24kg/m2; 4. Women who have not used contraception for more than 2 years and have not become pregnant; women who need to become pregnant but have agreed to use non‐drug contraception for the last 3 months; 5. Agree to regular postnatal examinations during pregnancy and acc

ChiCtr (2022). "Clinical efficacy of blastocyst culture supernatant transfer in hormone replacement frozen-thawed embryo transfer cycle: a prospective double-blind randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: experimental group:blastocyst culture supernatant transfer;control group:conventional culture medium transfer; CONDITION: female infertility PRIMARY OUTCOME: Live birth rate; SECONDARY OUTCOME: Clinical pregnancy rate;Early abortion rate; INCLUSION CRITERIA: 1. The first frozen embryo transfer; 2. Aged 20‐40 years; 3. Basic endocrine FSH<=10IU/L, BMI<=30; 4. At least one high‐quality blastocyst and blastocyst culture supernatant with D5 grade and above B3BB should be frozen; 5. Endometrial thickness >= 7mm and progesterone <= 1.0ng/ml on the day of secretory transformation.

ChiCtr (2022). "Clinical study of low intensity focused ultrasound in promoting endometrial repair after abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group :The control group received no treatment;Drug group:In the drug group, subjects were treated with Euthyrene‐drospirenone ethinylestradiol tablets, one tablet per day (3mg/0.02mg) after surgery, for 3 months. ;Low intensity focused ultrasound intervention group:Intra‐regional mobile therapy was carried out within 5cm of the symphysis pubis center at a speed of 1‐2cm/s, with the intervention time of 15 minutes each time, once a day, for a total of 7 treatments (once a day in the first three days after surgery, with treatment gear 3‐5; After 3 d;Electrical stimulation group:After surgery, the electrode was pasted on the uterine area, and the analgesic mode was adopted. The intervention lasted for 30 minutes, and the treatment lasted for 3 consecutive days. Then, the patients were treated twice a week for two weeks. The uterine rejuvenation mode was adopted, and the el; CONDITION: Clinical study of low intensity focused ultrasound in promoting endometrial repair after abortion PRIMARY OUTCOME: 1) Endometrial thickness examination [15] : Transvaginal ultrasonography was performed 3 weeks after surgery to evaluate the endometrial thickness of each group. 2) Hemodynamic indexes of endometrium: Transvaginal ultrasonography was performed 3 weeks after surgery to check the endometrial blood flow and subendometrial&#; SECONDARY OUTCOME: 1) Endometrial type and volume: Transvaginal ultrasonography was performed 3 weeks after surgery to evaluate the endometrial type ABC in each group, analyze the proportion of each type in each group, and calculate the endometrial volume by THREE‐DIMENSIONAL ultrasonography. 2) VAS pain score: pain score was&#; INCLUSION CRITERIA: 1. Ultrasound examination showed intrauterine pregnancy, live fetus, anterior uterus, 6‐10 weeks of gestation; 2. 18‐35 years old, less than 3 times of qing Dynasty; 3. Menstrual regularity within 3 months before pregnancy; 4. Voluntarily give up pregnancy and accept induced abortion.

ChiCtr (2022). "A clinical study on application of ciprofol and propfol in general anesthesia of painless abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Ciprofol group:Intravenous bolus injection of cyclopofol 0.4 mg/kg;Propofol group:Propofol injection 2.0mg/kg; CONDITION: N/A PRIMARY OUTCOME: Success rate of anesthesia induction; SECONDARY OUTCOME: Effects on respiratory and circulatory systems;Time of anesthesia induction;Recovery time after anesthesia;Time required to leave the hospital after anesthesia;Frequency and dose of ciprofol and propofol injection; INCLUSION CRITERIA: 1. Aged 18‐35 years; 2. American Anesthesiologist Classification (ASA) I‐II; 3. Outpatient patients undergoing elective general anesthesia induced abortion; 4. Pregnancy time is 6 to 10 weeks; 5. Body mass inde X(BMI) 18‐30kg/m^2; 6. Vital signs: respiratory rate >=10 and <=24 times/min; blood oxygen saturation (SpO2) >=95% when breathing air; systolic blood pressure (SBP) >=90mmHg and <=160mmHg; diastolic blood pressure (DBP) >=60mmHg and <=100mmHg; heart rate >=55 and <=100 beats/min; 7. Be able to understand the research process and method, and voluntarily participate in this research.

ChiCtr (2022). "The ED 95 of Esketamine in Outpatient-Induced Abortion Compared to Equivalent Sufentanil: a randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group one:esketamine;Group two:sufentanil;Group three:propofol; CONDITION: early pregnancy PRIMARY OUTCOME: dose of propofol; SECONDARY OUTCOME: time of operation;awakening time;heart rate;mean arterial pressure;pluse oxygen saturation;Ramsay sedation scores;visual analogue scale scores;Beck Depression Scale score;adverse effect; INCLUSION CRITERIA: 1. Women in the first trimester (7‐10 weeks) who planned to undergo painless abortion; 2. Women aged between 18 and 45; 3. BMI =18‐25kg/m2; 4. ASA classification was I‐II; 5. Voluntary participation in the study.

ChiCtr (2022). "Effect of local PRP injection on ovarian reserve and assisted reproductive outcomes: a randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:Injection of PRP;Control group:None; CONDITION: Diminished Ovarian Reserve PRIMARY OUTCOME: live birth rate; SECONDARY OUTCOME: number of eggs retrieved;2PN fertilization rate;available embryo rate;biochemical pregnancy rate;clinical pregnancy rate;ongoing pregnancy rate;miscarriage rate;embryo implantation rate;cycle cancellation rate; INCLUSION CRITERIA: 1. AFC < 5, AMH < 1.2ng/ml; 2. No pregnancy >=6 months without contraception; 3. The number of oocytes obtained by the previous standard regimen (antagonist and long regimen) was <=3; 4. The patient or his legal representative signed the informed consent form.

ChiCtr (2022). "Effect of routine hysteroscopy before IUI on live birth rate in infertile women with normal uterine cavity by ultrasound: a multicenter randomized clinical trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A:Perform hysteroscopy;Group B:Hysteroscopy not performed; CONDITION: Endometrial Diseases PRIMARY OUTCOME: live birth rate; SECONDARY OUTCOME: Complications of hysteroscopy and surgery ;Comfort tolerance after operation;miscarriage rate;Ectopic pregnancy rate ;Incidence of maternal complications during pregnanc;Incidence of neonatal complications;Cost of hysteroscopy ;Cost of IUI treatment ; INCLUSION CRITERIA: ?Infertility; ?IVF/ICSI assisted fertility treatment is planned for the first time; ?Aged 20 to 38 years; ?Accept and adhere to treatment and follow‐up.

ChiCtr (2022). "Effect of routine hysteroscopy before IVF/ICSI on live birth rate in infertile women with normal uterine cavity by ultrasound: a multicenter randomized clinical trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A :Perform Hysteroscopy;Group B:Without Hysteroscopy; CONDITION: Endometrial Diseases PRIMARY OUTCOME: live birth rate; SECONDARY OUTCOME: Complications of hysteroscopy and surgery;Pain score of operation;Comfort tolerance after operation;miscarriage rate;Ectopic pregnancy rate;Incidence of maternal complications during pregnancy;Incidence of neonatal complications;Cost of hysteroscopy;Cost of in vitro fertilization (IVF) treatment; INCLUSION CRITERIA: 1. Infertility; 2. IVF/ICSI assisted fertility treatment is planned for the first time; 3. Aged 20‐38 years; 4. Accept and adhere to treatment and follow‐up.

ChiCtr (2022). "Effect of Zhuyun Pill combined with dydrogesterone on early pregnancy outcome in threatened abortion: a single- center randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The experimental group:Zhuyun Pill + Dydrogesterone;The control group:Zhuyun Pill placebo + Dydrogesterone; CONDITION: threatened abortion PRIMARY OUTCOME: Early pregnancy embryo survival rate; SECONDARY OUTCOME: Blood ß‐hCG;progesterone;estradiol; INCLUSION CRITERIA: 1. Age between 25 and 40 years. 2. Positive urine pregnancy test or blood HCG test. 3. Early pregnancy (5‐8 weeks/35‐56 days) with vaginal bleeding, cervical os closure with or without abdominal pain and diagnostic ultrasound confirmation of intrauterine embryo or fetal survival. 4. The diagnosis of fetal leakage or fetal disturbance is consistent with the TCM diagnosis of renal deficiency type / spleen and kidney deficiency type. 5. No treatment was received for this preterm abortion. 6. The subject and her spouse are competent and willing to sign informed consent. 7. The subject will be randomised and will take the medication until the 10th week (70 days) of pregnancy as specified in the study protocol.

ChiCtr (2022). "Effect of Zishen Yufei wan in women with unexplained recurrent abortion: a randomized controlled double-blind clinical study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control:Dydrogesterone + placebo;Intervention group:Dydrogesterone + Zishen Yufei wan; CONDITION: unexplained recurrent abortion PRIMARY OUTCOME: live birth rate; INCLUSION CRITERIA: 1. Aged 20‐40 years; 2. Spontaneous abortion >= 2 consecutive times with the same partner; 3. Patients and their family members fully understood the content of the study and voluntarily signed informed consent; 4. Gestational age < 8 weeks.

ChiCtr (2022). "The efficacy and safety of cyclosporine in improving pregnancy outcome of patients with repeated embryo implantation failure: an open, randomized, controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group:Freezing embryo transfer (FET);experimental group:Freezing embryo transfer (FET)+cyclosporin A 50mg bid; CONDITION: repeated embryo implantation failure(RIF) PRIMARY OUTCOME: clinical pregnancy rate; SECONDARY OUTCOME: Embryo implantation rate;live birth rate;abortion rate;Blood ß‐HCG;pregnancy complication;Neonatal score and neonatal basic situation;immunological indexes; INCLUSION CRITERIA: 1.No clinical pregnancy was obtained after 2 or more transplants; 2.Hysteroscopy showed normal size and endometrium. 3.4 embryos at cleavage stage or 2 embryos at blastocyst stage were transplanted; 4.22‐35 years old; 5.The chromosome karyotype of both husband and wife has no obvious abnormality; 6.Semen examination of the male was normal; 7.Healthy four (TORCH) tests and no infectious diseases; 8.Subjects have clear consciousness and can cooperate with the experiment, complete medical records and sign informed consent;

ChiCtr (2022). "Efficacy of Pre-Treatment with Remimazolam on Prevention of Propofol-Induced Injection Pain in Patients Undergoing abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group 1 :remimazolam;Group 2:normal saline; CONDITION: propofol‐induced injection pain PRIMARY OUTCOME: Incidence of propofol injection pain;Adverse reactions; SECONDARY OUTCOME: Propofol injection pain intensity;vital signs;surgery time;recovery time; INCLUSION CRITERIA: 140 patients underwent elective painless abortion examination under general anesthesia, ASA grade I ‐II; Age is 18‐65 years old; BMI is 18‐28 kg/m2.

ChiCtr (2022). "Evaluation of efficacy and safety of granulocyte colony-stimulating factor in the treatment of patients with low ovarian reserve: a multicenter, randomized, double-blind, placebo-controlled clinical trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:G‐CSF;Control group:Normal saline; CONDITION: Diminished ovarian reserve PRIMARY OUTCOME: Optimal embryo rate; SECONDARY OUTCOME: Oocyte acquisition rate;Transplantable embryo rate;MII oocyte rate; INCLUSION CRITERIA: 1. Voluntary participation, understanding and signing of informed consent; 2. In line with IVF/ICSI indications; 3. Conform to one of the three can be: (1) 1.10 <= FSH <= 20; (2) Antral follicles <= 7; (3) AMH <= 2.0; 4. Aged 20‐40 years; 5. PPOS program to promote ovulation.

ChiCtr (2022). "Frozen-warmed embryo transfer after 6 or 7 days of progesterone administration for day 6 blastocysts in hormone replacement therapy cycles: a randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A:Embryos are transferred after 6 days of progesterone supplementation;Group B:Embryos are transferred after 7 days of progesterone supplementation; CONDITION: Female infertility PRIMARY OUTCOME: Live birth rate; SECONDARY OUTCOME: Biochemical pregnancy rate;Clinical pregnancy rate;Early miscarriage rate;Ectopic pregnancy rate;Multiple pregnancy rate;Neonatal outcome;Perinatal complications; INCLUSION CRITERIA: 1. Age at the time of oocyte retrieval between 20 and 40 years; 2. Having single frozen‐thawed blastocyst transfer in HRT cycles; 3. Both husband and wife fully understand and voluntarily participate in the study.

ChiCtr (2022). "Growth hormone improves the clinical outcome of in vitro fertilization and embryo transfer in elderly patients: a multicenter, open label, randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group N1:Patients receiving GH are going to be administered 18 IU/week sc on Day2 or Day3 of the previous menstrual cycle before IVF. After about 6 administrations, patients can receive 4 IU/day GH sc until HCG injection.;Group N2:Patients in Group N2 will start controlled ovarian hyperstimulation after being grouped without preliminary GH administration.; CONDITION: Ovarian dysfunction PRIMARY OUTCOME: Cumulative live birth rates; SECONDARY OUTCOME: Number of retrieved oocytes;Number of mature eggs;Number of fertilized eggs;Number of cleaved embryos;Number of high‐quality embryos;Endometrial thickness on hCG day;Implantation rate;Mild to severe OHSS;Viable intrauterine pregnancy;Ectopic pregnancy;Abortion;Stillbirth;Terminal pregnancy;Live birth;Gestational age at birth;Birth weight;Neonatal mortality;Important congenital malformations;cleavage rate;high‐quality embryo rate;clinical pregnancy rate;ongoing pregnancy rate;cycle cancellation rate;Ectopic pregnancy rate;miscarriage rate;live birth rate;risk of low birth weight;preterm birth rate;OHSS incidence; INCLUSION CRITERIA: 1.Infertile women planning IVF / ICSI for the first time 2.Age: 35‐42 years old 3.GH has not been used in the past 2 months

ChiCtr (2022). "Intervention of Rational Emotional Behavior Therapy (REBT) for Psychological Distress among Patients with Early Threatened Miscarriage after Invitro Fertilization-Embryo Transfer (IVF-ET)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:Rational emotional behavior therapy + routine nursing;Control group:Routine nursing; CONDITION: infertility PRIMARY OUTCOME: anxiety;depression; INCLUSION CRITERIA: 1. Patients who met the diagnostic criteria for early threatened abortion before 12 weeks of gestation after IVF‐ET surgery; 2. Self‐rating anxiety scale score >=50 points (standard score); 3. Have certain audiovisual, speaking, reading and writing ability, can cooperate with research; 4. Sign informed consent; 5. Volunteer to participate in the study.

ChiCtr (2022). "A multicenter, randomized, double-blind study on the efficacy and safety of Gongxuening capsules in reducing postoperative bleeding after induced abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:Gongxuening Capsule;Control group:Placebo capsule; CONDITION: postoperative bleeding after induced abortion PRIMARY OUTCOME: Vaginal bleeding volume; SECONDARY OUTCOME: Bleeding time;Menstrual rehydration time;Endometrial repair;Complication;Safety index; INCLUSION CRITERIA: 1. 20 years old <= age <= 40 years old; 2. Intrauterine pregnancy <= 10 weeks (note: preoperative ultrasound fetal sac < 1 cm and fetal bud < 3 cm), women who require abortion without contraindications; 3. Regular menstrual cycle in the past si Xmonths, no recent (si Xmonths) history of induced abortion; 4. The subjects voluntarily signed the informed consent.

ChiCtr (2022). "A multicenter, randomized, double-blind, dose-parallel control exploratory phase IIa clinical trial to evaluate the efficacy and safety of Zishen Yutai Pills in the treatment of diminished ovarian reserve (spleen and kidney deficiency syndrome)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: high dose group:Zishen Yutai Pills ;low dose group:Zishen Yutai Pills ;Placebo group:Placebo; CONDITION: diminished ovarian reserve PRIMARY OUTCOME: anti‐mullerian hormone; SECONDARY OUTCOME: Antral follicle count;FSH normalization rate;FSH/LH ratio;five se Xhormones (FSH, LH, E2, PRL, T);ovarian volume;serum inhibin B;Normalization rate of menstrual cycle (rate of patients with menstrual cycle of 28‐25 days);menstrual score;TCM syndrome score and curative effect;progesterone;endometrial status;adverse events;vital signs;physical examination;blood routine examination;routine urine and urine sediment microscopy;routine stool+occult blood examination;liver function;renal function;12‐lead ECG examination;Breast ultrasound; INCLUSION CRITERIA: 1. Conform to the diagnosis of diminished ovarian reserve; 2. TCM syndrome differentiation is spleen and kidney deficiency syndrome; 3. Females aged < 40 years with a history of sexual life; 4. The patient voluntarily participates in this clinical trial, gives informed consent and signs a written informed consent form.

ChiCtr (2022). "Natural cycle frozen-thawed embryo transfer: luteal support or not? A multi-center, non-inferiority, randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Luteal support group:Patients receive vaginal progesterone extended‐release gel and intramuscular progesterone from the first day after ovulation;No luteal support group:None; CONDITION: Natural cycle frozen‐thawed embryo transfer PRIMARY OUTCOME: Ongoing pregnancy rate; SECONDARY OUTCOME: Positive pregnancy rate;Embryo implantation rate;Incidence of threatened abortion;Pregnancy loss rate;Ectopic pregnancy rate;Multiple pregnancy rate;Live birth rate;Pregnancy‐related complications;Obstetric complications; INCLUSION CRITERIA: 1. Ovulation regularity; 2. At least one embryo is available for transfer.

ChiCtr (2022). "A randomized controlled trial of acupuncture in the treatment of ovarian reserve dysfunction." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:The two acupoints were used alternately;Control group:Superficial puncture of 2‐3mm on all acupoints; CONDITION: Diminished ovarian reserve (DOR) PRIMARY OUTCOME: Antral follicle count; SECONDARY OUTCOME: Follicle stimulating hormone;Luteinizing hormone;Estradiol;Progesterone;Arterial resistance index;Systolic / diastolic blood flow velocity ratio;Peak systolic blood flow velocity;Anti‐mullerian hormone;Self‐Rating Anxiety Scale;Clinical pregnancy rate;Available embryo rate;Egg number;High‐quality embryo rate;Embryo implantation rate;Biochemical pregnancy rate;Early pregnancy loss rate;Sustained pregnancy rate; INCLUSION CRITERIA: 1. Aged >=20 and <40 years; 2. Meet the diagnostic criteria of DOR; 3. Volunteer to participate in the trial and sign the informed consent.

ChiCtr (2023). "Alleviating Postoperative Pain after Laparoscopic Myomectomy: the Role of Dexamethasone and Ropivacaine in Superior Hypogastric Plexus Block." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control Group:10ml: 100mg ropivacaine 20ml in the SHP area;Treatment Group:10ml: 100mg ropivacaine 19ml + 1ml: 5mg dexamethasone 1ml in the SHP area; CONDITION: Postoperative Pain after Laparoscopic Myomectomy PRIMARY OUTCOME: VAS score; SECONDARY OUTCOME: cumulative consumption of non‐steroidal anti‐inflammatory drugs or opioids within 48 hours postoperatively;postoperative adverse reactions;intraoperative fluid volume, urine output, and blood loss;first postoperative exhaust time;first postoperative ambulation; INCLUSION CRITERIA: 1.Patients undergoing elective laparoscopic myomectomy for uterine fibroids. 2.Number of fibroids not exceeding 10. 3.ASA grade of I‐III. 4.Age between 18 to 55 years. 5.Willingness to participate in the study and provide signed informed consent. 6.Not currently participating in other clinical trials.

ChiCtr (2023). "Analysis of pregnancy outcomes in patients with polycystic ovary syndrome after clinical intervention with human assisted reproductive technology." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment group:Pharmacological intervention;Control group:N/A; CONDITION: Polycystic ovary syndrome PRIMARY OUTCOME: Clinical pregnancy rate;Abortion rate;Oocyte tetrieval rate;High quality embryo number; INCLUSION CRITERIA: PCOS can be defined if at least 2 of the following 3 criteria are present: ? Watery ovulation or chronic anovulation (OA); ? Clinical manifestations of hyperandrogenemia or hyperandrogenism (HA); ? Ultrasonic monitoring of polycystic ovarian changes (PCO)

ChiCtr (2023). "Application of dural puncture epidural technique for elderly orthopedic surgery of lower limbs." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Epidural group:Anesthesia method: epidural block; Anesthetic drugs: 0.5% ropivacaine +1% lidocaine 8‐12ml.;Combined spinal epidural anesthesia group:Methods of anesthesia: combined spinal‐epidural block; Anesthesia: 0.5% ropivacaine + sterile water for injection 2‐2.4ml.;Dural puncture epidural block group:Anesthesia method: dural puncture epidural block; Anesthetic drugs: 0.5% ropivacaine +1% lidocaine 8‐12ml.; CONDITION: elderly orthopedic surgery of lower limbs PRIMARY OUTCOME: Time from sensory block plane to T10; SECONDARY OUTCOME: Highest level of anesthesia;Blood pressure;Heart rate;Sedation score;Pain score;Effect of anesthesia;The amount of local anesthetic used;Adverse reactions; INCLUSION CRITERIA: (1)All patients were American Society of Anesthesiologists physical status 1‐?, aged =60 years, undergoing lower extremity orthopedic surgery. (2) There were no contraindications of operation and spinal anesthesia; (3) Complete clinical data and signed informed consent.

ChiCtr (2023). "Application of sacrococcygeal ice compress based on posterior acoustic pathway damage decrease on focused ultrasound ablation (FUAS): a randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: sacrococcygeal ice compress:Intraoperative and postoperative ice compress on sacrococcygeal region;blank control:none; CONDITION: Uterine leiomyoma PRIMARY OUTCOME: visual analogue scale,VAS; SECONDARY OUTCOME: Postoperative pelvic magnetic resonance imaging; INCLUSION CRITERIA: Patients with uterine leiomyomas diagnosed by pelvic color Doppler ultrasound and pelvic magnetic resonance, agree to receive FUAS and sacrococcygeal ice compress, no severe systemic diseases, understand the VAS system, informed consent.

ChiCtr (2023). "Application of ultrasound-guided pudendal nerve block in transvaginal pelvic floor reconstruction." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: experimental group:ultrasound‐guided pudendal nerve block;control group:general anesthesia; CONDITION: Perioperative pain in transvaginal pelvic floor reconstruction PRIMARY OUTCOME: Number of PCA;Number of flurbiprofen axetil for rescue analgesia; SECONDARY OUTCOME: pain score;Consumption of remifentanil;Consumption of propofol;catheter‐related bladder discomfort(CRBD);Incidence of adverse reactions;Leaving bed time;Length of postoperative hospital stay;Postoperative analgesia satisfaction; INCLUSION CRITERIA: 1. ASA I‐II 2. Over 60 years old 3. BMI<30kg/m2 4. Patients with pelvic organ prolapse who intend to undergo transvaginal hysterectomy and/or anterior/posterior vaginal wall repair under general anesthesia

ChiCtr (2023). "Application research on improvement of voiding dysfunction after radical operation of cervical cancer based on the original new method of core muscle strength training." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: core muscle strength training group:In the core muscle training group, the subject was placed in a supine position with knees bent at 90° and feet shoulder‐width apart. An elastic band was placed at the proximal end of the knee joint, and the patient was asked to do the hip abduction and external rotation exercise first, maintaining the resistance of the elastic band at 1.5‐2 kg. Slowly, the abdominal contraction, chest inhibition, and anal lift after exhalation were implemented to promote the contraction of transverse abdominal muscles and pelvic floor muscles at the same time, maintaining 5 seconds for one time, 20 times for one group, and two groups were implemented each time.;Regular rehabilitation training group:The conventional rehabilitation training group performed plyometric intervention at a load that could be repeatedly completed 8‐12 times (approximately equal to 60‐70% 1RM:1 repetition maximum), and 2 sets of each of the 9 resistance exercises were performed 8 to 12 times, respectively. The duration of each intervention was 15 minutes, and the intervention was performed 5 times per week for 12 weeks of treatment.; CONDITION: Application research on improvement of voiding dysfunction after radical operation of cervical cancer based on the original new method of core muscle strength training PRIMARY OUTCOME: Urinary function indicators;Postoperative urinary catheter replacement rate in patients undergoing radical cervical cancer surgery;Mesure deHandicap Urinaire; SECONDARY OUTCOME: Imaging indicators of the transversus abdominis muscle; INCLUSION CRITERIA: ?. Age 18 to 65 years old; ?. Meet the relevant diagnostic criteria in the Guidelines for the diagnosis and treatment of cervical cancer (4th edition) [26]; ?. Radical cervical cancer surgery with postoperative catheterization; ?. No contraindications to surgery; ?. Complete clinical information; ?. Voluntary participation and signed informed consent.

ChiCtr (2023). "Clinical effect of ultrasound-guided paracervical nerve block in the treatment of cervical cancer patients with painless postimplantation." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control Group:Bilateral paracervical nerve block was not performed;Group:Bilateral paracervical nerve block was performed ; CONDITION: cervical cancer PRIMARY OUTCOME: VAS score;Incidence of hypoxemia;WHO Pain scale;Nausea and vomiting occur;Physical activity condition;the satisfaction of patients;Surgeon satisfaction; SECONDARY OUTCOME: Circulatory adverse events;heart rate;mean arterial pressure;operative time; INCLUSION CRITERIA: ASA ? ‐ ? level;Patients receiving painless post‐implantation therapy for cervical cancer;Aged 18‐75 years;They agreed to participate in the study and signed the informed consent form

ChiCtr (2023). "Clinical efficacy of diaphragmatic breathing training combined with biofeedback electrical stimulation therapy for postpartum stress urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Vaginal delivery experimental group:biofeedback electric stimulation therapy combine with diaphragmatic breathing training ;Vaginal delivery control group:biofeedback electric stimulation therapy;Caesarean section experimental group:biofeedback electric stimulation therapy combine with diaphragmatic breathing training ;Caesarean section control group:biofeedback electric stimulation therapy; CONDITION: Postpartum stress urinary incontinence PRIMARY OUTCOME: Digital assessment of pelvic floor muscle strength;pelvic organ prolapse quantification;pelvic floor muscle bioelectrical activity; SECONDARY OUTCOME: pelvic floor distress inventory‐short form 20; INCLUSION CRITERIA: ?Newborn mothers who have given birth for more than 3 months. ?Age 22 to 35 years. ?Lochia drains. ?Full‐term delivery, singleton. ?Newborn baby weighing 2500‐3500g. ?Prenatal Body Mass Inde Xof between 18.5 and 23.9. ?Simple mild or moderate stress urinary incontinence or a diagnosis of pelvic. ?prolapse I‐II using pelvic organ ?prolapse quantification (POP‐Q) in women. ?No previous history of pelvic surgery or coexisting pelvic infections, no combined heart disease, diabetes, hypertension during pregnancy, no postpartum dysfunctional disorders prior to pregnancy.

ChiCtr (2023). "Clinical observation of functional magnetic stimulation of pelvic floor in treatment of stress urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group:Perform pelvic floor muscle training according to the pelvic floor muscle training recommended by the urinary incontine.;observation group:On the basis of pelvic floor muscle training, pelvic floor functional magnetic stimulation (sacral nerve magnetic stimulation). ; CONDITION: stress urinary incontinence PRIMARY OUTCOME: International Consultation on Incontinence Questionnaires; SECONDARY OUTCOME: one hour urine pad test;Pelvic floor surface electromyography; INCLUSION CRITERIA: ? Postpartum stress urinary incontinence, in line with the relevant diagnostic criteria; ? After =1 month (simple drug treatment or simple pelvic floor muscle function training) conservative effect is not significant; ? Agree not to receive any other treatment outside the program during the period of participation in the program.

ChiCtr (2023). "Clinical Observation on Auricular Acupressure for Primary Dysmenorrhea." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment group:Auricular acupressure;Control group:Placebo auricular acupressure; CONDITION: Primary Dysmenorrhea PRIMARY OUTCOME: visual analogue scale, VAS; SECONDARY OUTCOME: Menstrual Distress Questionnaire;usage rate of analgesics;blind assessment;safety evaluation;Onset time of analgesic effect;Duration of pain; INCLUSION CRITERIA: (1) Patients who meet the diagnostic criteria for PD; (2) Between the ages of 18 and 30; (3) With regular menstrual cycle of 28±7 days, menstrual period of 3‐7 days, and the pain starting on the first day of the cycle; (4) Haven't received treatment for PD within a month prior to enrollment; (5) VAS score =4; (6) Voluntarily participate in the study and sign the informed consent.

ChiCtr (2023). "Clinical study of antibiotics combined with antioxidants in the treatment of infertility patients with chronic endometritis after repeated transplantation failure." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A :doxycycline 100 mg Bid + metronidazole 400 mg Bid + cefdinir 100 mg tid for 14 days;Group B:doxycycline 100 mg Bid + metronidazole 400 mg Bid + cefdinir 100 mg tid + vitamin E 500 mg Bid + vitamin C 500 mg Bid for 14 days; CONDITION: Reproductive endocrine PRIMARY OUTCOME: live birth rate; SECONDARY OUTCOME: ongoing pregnancy rate;positive hCG rate;implantation rate;early miscarriage rate;clinical pregnancy rate; INCLUSION CRITERIA: 1. Transplantation cycle =2; 2. Patients with endometritis

ChiCtr (2023). "Clinical study of Bushen Huoxue Prescription on treatment mechanism and progeny of unexplained recurrent abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Bushen Huoxue prescription combined with aspirin group:Bushen Huoxue prescription combined with aspirin for 3 months;Bushen Huoxue formula combined with aspirin placebo group:Bushen Huoxue prescription combined with aspirin placebo treatment for 3 months;Bushen Huoxue formula placebo combined with aspirin group:Bushen Huoxue prescription placebo combined with aspirin;Bushen Huoxue prescription placebo combined with aspirin placebo group:Bushen Huoxue prescription placebo combined with aspirin placebo was administered for 3 months; CONDITION: Unexplained Recurrent Spontaneous Abortion PRIMARY OUTCOME: Factors associated with angiogenesis;Factors associated with iron death; SECONDARY OUTCOME: Coagulation index;Uterine arterial blood perfusion;Safety index; INCLUSION CRITERIA: (1) Women of childbearing age, aged 20‐40 years; (2) Normal menstrual cycle (28 30 days); (3) Urine pregnancy test is negative, blood ß‐HCG < 5IU/L, consent to use contraceptives during the medication; (4) The diagnostic criteria of URSA Western medicine and syndrome of kidney deficiency and blood stasis of slippery fetus were met; (5) Sign informed consent.

ChiCtr (2023). "Clinical study on perioperative analgesia of butorphanol in patients with ovarian cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: 1:Sufentanil 0.04 µg·kg‐1·h‐1;2:Butorphanol 3.0ug·kg‐1·h‐1;3:Butorphanol 3.5ug·kg‐1·h‐1;4:Butorphanol 4.0ug·kg‐1·h‐1; CONDITION: ovarian cancer PRIMARY OUTCOME: Visual Analogue Scale/Score,; SECONDARY OUTCOME: adverse reactions;rescue analgesia;CD4+;CD8+;CA‐125;HE4;Inflammatory factor; INCLUSION CRITERIA: ?ASA grade?‐?; (2) Patient compliance was good; (3) Postoperative pathological examination confirmed ovarian cancer. (4) No history of drug allergy; ?FIGO Grade I‐III; patients aged 18‐65.

ChiCtr (2023). "Clinical study on the efficacy and safety of remazolam besylate for induction and maintenance of general anesthesia in gynecological laparoscopic surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:Remazolam sedation;Control group:Propofol sedation; CONDITION: Gynecological uterine and adnexal diseases PRIMARY OUTCOME: Incidence of intraoperative hypotension; SECONDARY OUTCOME: Vital signs;Anesthesia wake time;Adverse reactions; INCLUSION CRITERIA: 1. Patients undergoing gynecological laparoscopic general anesthesia surgery (except for patients with malignant tumors); 2. Age 18‐60 years; 3 Body mass inde X(BMI): 18.5‐30 kg/m^2; 4 American Society of Anesthesiologists Grading (ASA) Grades I‐III; 5. Subjects voluntarily participate in the trial and sign the informed consent form of the trial.

ChiCtr (2023). "Clinical study on the immediate analgesic effect of acupuncture in the treatment of acute dysmenorrhea." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A:acupuncture;Group B:Sham‐acupuncture; CONDITION: dysmenorrhea PRIMARY OUTCOME: Analgesic efficiency at 10 minutes; SECONDARY OUTCOME: Analgesic efficiency at0‐1?2, 4, 6, 8min time points;Visual Analog Score(VAS);Blind evaluation;Evaluation of compliance; INCLUSION CRITERIA: (1)Meet the diagnostic criteria for primary dysmenorrhea and are experiencing acute attacks of dysmenorrhea; (2)Age 14‐35 years; (3)Visual analog score (VAS) >= 4; (4)Have not been treated with acupuncture and taken analgesic medication; (5)Voluntarily participated in this study and signed the informed consent, family informed consent is required for those under 18 years of age. Note: Patients who meet the above 5 items at the same time may be included in this study.

ChiCtr (2023). "A clinical study on the prevention and treatment of vulvovaginal candidiasis in women with Azmasol." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment group 1:Oral fluconazole 150mg once a day for 1 day and vaginal miconazole 400mg once a night for 3 days;;Treatment group 2:Oral fluconazole 150mg, once a day for 1 day; vaginal miconazole 400mg, once a night for 3 days; oral Azmasol , 2 pills twice a day for 6 days; if symptoms are effectively controlled after 7 days from the first treatment, continue oral Azmasol 1 pill daily for 12 weeks for consolidation.;Treatment group 3:Vaginal miconazole suppositories 400mg once a night for 3 days and oral Azmasol, 2 sticks twice a day for 6 days;; CONDITION: vulvovaginal candidiasis PRIMARY OUTCOME: Clinical cure rate;Compound cure rate; SECONDARY OUTCOME: Clinical improvement;Microbial clearance; INCLUSION CRITERIA: 1. Healthy women who are sexually active; 2. 18 years of age or older; 3. Have not consumed cranberry juice, polyphenols or antioxidant supplements within the past 2 weeks; 4. = 2 recurrent episodes of vulvovaginal candidiasis in the past 6 months; or 5. = 3 episodes of recurrent vulvovaginal candidiasis in the past 12 months.

ChiCtr (2023). "Comparative study on the effectiveness of two surgical methods for early cervical cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: TARH:TARH;Laparoscopic surgery based on the open stateGasless TLRH:Laparoscopic surgery based on the open state; CONDITION: Early Stage Cervical Cancer PRIMARY OUTCOME: Disease free survival;Length of stay; SECONDARY OUTCOME: Recurrence rates;Postoperative pain ;The Quality of Life;Operation time;Estimated blood loss;operative complications;The levels of CD4 + T lymphocytes, NK cells and CD4 + CD25 high CD127 low Treg;Hemodynamic parameters;MAP;SV;Costs; INCLUSION CRITERIA: Patients at least 18 years of age with adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the cervix, ECOG performance status of 0‐1, and FIGO (2018) clinical stage IA1 disease with lymphovascular space invasion, IA2 disease, or IB1 disease (<2 cm and limited to the cervix) were randomized 1:1 to open or minimally invasive radical hysterectomy. Patients could undergo either a type II or a type III radical hysterectomy (Piver classification) and pelvic lymphadenectomy. Postoperative adjuvant radiation therapy was recommended according to the Sedlis criteria, which are widely accepted.

ChiCtr (2023). "Comparison of the clinical outcomes in PCOS patients with letrozole resistance undergoing ovulation induction using letrozole "stair-step"protocol versus traditional gonadotropin protocol." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: study group:letrozole;control group:Gn protocol; CONDITION: polycystic ovarian syndrome PRIMARY OUTCOME: Multifollicular development rate; SECONDARY OUTCOME: monofollicular development rate; ovulation rate;cancellation rate;OHSS ;clinical pregnancy rate; INCLUSION CRITERIA: aged younger than 40 years old;PCOS patients with letrozole resistance

ChiCtr (2023). "Construction of a prevention plan for lower limb lymphedema in patients with gynecological malignant tumors after surgery and a multicenter clinical application study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: experimental group:To implement the established prevention program of lower limb lymphedema for gynecological malignant tumor patients after operation ;Control group:Routine postoperative care and treatment; CONDITION: Gynecology malignant tumor PRIMARY OUTCOME: Incidence of lower limb lymphedema;Stage of lower limb lymphedema; SECONDARY OUTCOME: Self‐reported symptoms;Life quality;Brief fatigue scale score; INCLUSION CRITERIA: Histopathological diagnosis of cervical cancer, endometrial cancer, vulvar cancer, ovarian cancer; Surgical treatment with pelvic or inguinal or aortic lymphadenectomy; =18 years of age; Volunteer.

ChiCtr (2023). "Effect and clinical efficacy evaluation of Tiao Shen Ning Xin Acupuncture on insomnia and anxiety comorbidity in patients with gynecological tumor chemotherapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment Group:Electroacupuncture combined with cognitive behavioral therapy for insomnia;Control group:Sham electroacupuncture combined with cognitive behavioral therapy for insomnia; CONDITION: Insomnia‐anxiety comorbidity PRIMARY OUTCOME: pittsburgh sleep quality inde,PSQI ; Athens Insomnia Scale,AIS;;Hamilton Anxiety Rating Scale,HAMA; SECONDARY OUTCOME: Sleep monitoring bracelet (heart rate, deep sleep time, light sleep time, REM time); INCLUSION CRITERIA: (1) Patients diagnosed with gynecological tumors (ovarian cancer, cervical cancer, endometrial cancer, vulvar malignancy, vaginal malignancy, uterine sarcoma, gestational trophoblastic tumor, etc.) requiring chemotherapy, insomnia and anxiety according to pathology; (2) Aged between 20 and 70 years old (including 20 and 70 years old); (3) Subject agrees and signs informed consent.

ChiCtr (2023). "The effect of corrective pelvic training in conjunction with biofeedback electrical stimulation on postpartum stress urinary incontinence in accordance with the regional dependency theory through a randomised controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group:Biofeedback electrical stimulation ;Experimental group 1:Combined biofeedback electrical stimulation in neutral pelvic position;Experimental group 2:Corrective pelvic position training combined with neutral pelvic position and biofeedback electrical stimulation; CONDITION: Postpartum stress urinary incontinence PRIMARY OUTCOME: Pelvic floor electromyography Glazer assessment test; SECONDARY OUTCOME: pelvic floor distress inventory‐short form 20, PFDI‐20;International Consultation on Incontinence Questionnaire‐Urinary Incontinence Short Form , ICI‐Q‐SF; INCLUSION CRITERIA: ?Patients were all primiparous women who returned 42 days after vaginal delivery and all had a single full‐term normal birth; ?were assessed by the postural assessment system as having anterior/posterior pelvic tilt, lateral pelvic tilt and pelvic rotation; ? were diagnosed with pelvic floor dysfunction with stress urinary incontinence; accepted the treatment offered by the hospital with complete data on the subject; ?and had normal cognitive abilities and could communicate normally.

ChiCtr (2023). "Effect of dexamethasone combined with different drugs as adjuvant of local anesthetic on TAP nerve block." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group D:At the end of the operation, dexamethasone 10mg was given intravenously, followed by bilateral TAPB and unilateral 0.375% ropivacaine 20ml under ultrasound guidance.;Group DD:At the end of the operation, dexamethasone 10mg was given intravenously, followed by bilateral TAPB and unilateral 0.375% ropivacaine+dexmedetomidine 30ug, 20ml under ultrasound guidance.;Group DE:At the end of the operation, dexamethasone 10mg was given intravenously, followed by bilateral TAPB and unilateral 0.375% ropivacaine+magnesium sulfate 200mg, 20ml under ultrasound guidance.;Group DM:At the end of the operation, dexamethasone 10mg was given intravenously, followed by ultrasound‐guided bilateral TAPB, unilateral 0.375% ropivacaine+dexmedetomidine 30ug+ magnesium sulfate 200mg, 20ml.; CONDITION: Tubal ovarian abscess; Gynecological tumor; Pain after laparoscopic surgery (gynecology, gastrointestinal surgery) PRIMARY OUTCOME: The completion time of nerve block from the first time the patient presses the analgesia pump.; SECONDARY OUTCOME: Sleep score;Opioid dosage;Pain score;Analgesic pump pressing times;Sedation score; INCLUSION CRITERIA: Patients undergoing minimally invasive lower abdominal surgery (gynecology, colorectal). INCLUSION CRITERIA: (1) 18‐65 years old; (2) BMI 18‐30; (3) ASA level 1‐3; (4) No diabetes or diabetes regularity; (5) No history of chronic pain, alcohol abuse or drug abuse; (6)Those who voluntarily accept postoperative intravenous analgesia.(7)Once agreed to accept this study.

ChiCtr (2023). "Effect of dexmedetomidine as an adjuvant in transversus abdominis plane block on postoperative recovery in gynecological patients undergoing laparoscopic surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A:TAPB with dexmedetomidine and ropivacaine before skin incision;Group B:Ropivacaine in TAPB before peeling;Group C:Ropivacaine in TAPB after sewing;Group D:TAPB free; CONDITION: Ovarian cyst, uterine fibroid, cervical cancer PRIMARY OUTCOME: Pain scores;Restore quality; SECONDARY OUTCOME: Infection index;hemodynamics;Narcotic drug usage;Postoperative recovery;Postoperative analgesic effect;Side effects and adverse reactions;Early recovery index;Incidence of POCD; INCLUSION CRITERIA: (1) Age range from 18 to 80 years old; (2) Patients who are conscious, voluntarily participate in this study and sign informed consent; (3) American Society of Anesthesiologists (ASA) Class I to III; (4) Operation duration >=60min; (5) patients without serious cardiovascular and cerebrovascular diseases and respiratory and circulatory system diseases; (6) Patients without obvious contraindications to anesthesia.

ChiCtr (2023). "The effect of different doses of esketamine on the incidence and quality of recovery in patients with cervical cancer: a double-blind, randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Saline group(Group N):Single intravenous injection of 10ml of saline was given 10min before skin cutting;Eesketamine 0.1 mg / kg group(Group A):Single intravenous injection of esketamine 0.1 mg / kg (diluted to 10ml) 10min before skin cutting;Eesketamine 0.2 mg / kg group(Group B):Single intravenous injection of esketamine 0.2 mg / kg (diluted to 10ml) 10min before skin cutting;Eesketamine 0.4 mg / kg group(Group C):Single intravenous injection of esketamine 0.4 mg / kg (diluted to 10ml) 10min before skin cutting; CONDITION: Cervical cancer PRIMARY OUTCOME: Prevalence of depression within 7 days after surgery; SECONDARY OUTCOME: Self‐rating Scale (SDS) at 1d, 3d, 5d and 7d;Recovery quality scale score at 1d, 3d, 5d and 7d (QoR‐15);Sleep quality score on the 1d, 3d, 5d and 7d after operation;Postoperative drug withdrawal‐extubation time;In‐out PACU time;Time of first rescue analgesia after operation;The amount of remedial analgesic drugs at 1d, 3d, 5d and 7d;Length of postoperative hospitalization;Intraoperative remifentanil dosage;Intraoperative propofol dosage;Intraoperative mean arterial pressure; INCLUSION CRITERIA: 1. Age: 30 65 years old; 2. ASA grades I to II; 3. Cervical cancer stage III and below; 4.BMI 18 28 kg/m²; 5. Be able to complete the questionnaire independently and voluntarily sign the informed consent form to participate in this trial study.

ChiCtr (2023). "Effect of Esketamine on depression and perioperative neuropsychiatric disorders in patients with malignant tumors." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: group E :After anesthesia induction, group E was given 0.5mg/kg Esketamine (esketamine diluted to 10mg/ml) and 100ml postoperative analgesic pump, and the analgesic formula was Esketamine 2mg/kg(Esketamine diluted to 10mg/ml) + Sufentanil 2.5µg/kg+ flurbiprofen ester 2mg/kg+ tolanisetron 10mg+ normal saline;group C :After anesthesia induction, group C was given 0.05ml/kg normal saline and 100ml postoperative analgesic pump. The analgesic formula was Sufentanil 2.5µg/kg+ flurbiprofen ester 2mg/kg+ toranisetron 10mg+ normal saline; CONDITION: Perioperative neurocognitive dysfunction PRIMARY OUTCOME: Incidence of postoperative delirium;Neuropsychological testing;The occurrence of postoperative depression; SECONDARY OUTCOME: Scores on telephone interview for cognitive status‐modified;Numeric rating scale score;PCA press times;Intraoperative anesthetic dosage;Use of vasoactive drugs;Intraoperative fluid entry and exit volume;Duration of operation and anesthesia;Postoperative adverse reaction;All‐cause mortality, readmission rate and secondary operation rate 30 days after surgery;Rate of tumor recurrence and metastasis within 3 months after surgery;Postoperative recovery quality; INCLUSION CRITERIA: 1. From February 1, 2021 to August 31, 2022, patients aged over 60 years with malignant tumors were selected for surgery in Guangxi Medical University Cancer Hospital (gynecological tumors, gastrointestinal tumors, thoracic surgery, urological surgery), no gender limit; 2. ASA ? ‐?, BMI 18‐25kg/m^2; 3. Years of education >=6 years; 4. Pathological report diagnosed cancer; 5. Expected operation time >=2 hours and postoperative hospital stay > 7 days.

ChiCtr (2023). "Effect of hydroxychloroquine sulfate on pregnancy outcomes in patients with repeated implantation failure and ANA positive: a double-blind, randomized, placebo-controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Hydroxychloroquine sulfate group:Hydroxychloroquine sulfate;Placebo group :Placebo; CONDITION: patients with repeated implantation failure and ANA positive PRIMARY OUTCOME: clinicalpregnancy; SECONDARY OUTCOME: hCG positive rate;Early abortion rate;Sustained pregnancy rate; INCLUSION CRITERIA: 1. Patients who failed to obtain clinical pregnancy after at least 2 fresh or freeze‐thaw embryo transfer cycles and at least 2 high‐quality cleavage embryos or 1 high‐quality blastula each time 2. ANA titer >= 1:80 was detected by indirect immunofluorescence at least 4 weeks interval >=2 times; 3. IVF treatment was performed at the reproductive center for the second pregnancy.

ChiCtr (2023). "Effect of intravenous dexamethasone on sleep quality after open gynecological surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: treatment group:intravenous dexamethasone 8mg;control group :intravenous saline; CONDITION: Postoperative sleep disturbance PRIMARY OUTCOME: Sleep Quality ; SECONDARY OUTCOME: Depression and Anxiety Scale;pain score;Consumption of opioid analgesics (sufentanil);Blood glucose values; INCLUSION CRITERIA: 18‐70 years old, ASA grade I‐III, open gynecological tumor surgery, BMI < 35

ChiCtr (2023). "Effect of intravenous lidocaine on propofol Schnider mode TCI inhibition of cervical dilatation during induced abortion." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: lidocaine group:Intravenous injection of lidocaine 1mg/kg;Control group:Physiological saline; CONDITION: Anesthesia for patients undergoing painless induced abortion PRIMARY OUTCOME: Propofol's EC50; SECONDARY OUTCOME: Vital signs;Wake up of time;The operation time;Pain of propofol injection;VAS pain score; INCLUSION CRITERIA: Patients with primary induced abortion, 6‐9 weeks gestation, age =35 years old, body mass inde X18‐25 kg/m2, ASA grade I‐? were selected.

ChiCtr (2023). "Effect of Kuntai Capsule on intestinal microecology and insulin resistance in patients with polycystic ovary syndrome: a multicenter, randomized and parallel controlled clinical study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Al group:Orally take Kuntai capsule, 4 pills / time, 3 times / day, for three months, non‐stop during menstrual time.;A2 group:Orally take Kuntai capsule, 4 pills / time, 3 times / day, for three months, non‐stop during menstrual time.;B group:no; CONDITION: PCOS PRIMARY OUTCOME: flora analysis in stool samples;blood fat ; SECONDARY OUTCOME: se Xhormone;Serum glucose;Fasting serum insulin;OGTT;BMI;WHR ;Menstruation scores;acne scores;hirsutism scores; INCLUSION CRITERIA: 1Patients meet the diagnostic criteria of the 2003 European Society for Human Reproductive and Embryology in Rotterdam and the American Society of Reproductive Medicine (ESHRE / ASRM), which requires any 2 of the following 3 items: 1) rare ovulation and / or anovulation; 2) clinical manifestations and / or excessive androgens; or 3) ultrasound detection of ovarian polycystic changes: with =12 follicles of 2‐9mm in diameter in one /both ovaries,ovarian volume= 10 ml in one /both ovaries;2. Patients are evaluated by the steady‐state model insulin resistance inde X(homeostasis model assessment‐insulin resistance index, HOMA‐IR), HOMA‐IR= 2.69 is regarded as IR, otherwise not IR;3. Women aged between the ages of 18 and 40 years;4. 18=BMI=35 kg/m2;5.Patients have no family planning in recent 3 months;6. Patients are ability to follow the protocol for treatment, examination, and follow‐up;7.Patients are consent, voluntary to be tested.

ChiCtr (2023). "Effect of low-dose esketamine on postoperative quality of recovery in gynecological laparoscopic patients." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group (Esketamine group ):Esketamine is administered an 0.25mg/kg prior to deemectomy after anesthesia and then maintained at 0.1mg/kg/h.The drug was discontinued about 15minutes before the end of surgery.;Control group :Normal saline was administered an 0.25mg/kg prior to deemectomy after of anesthesia and then maintained at 0.1mg/kg/h.The drug is discontinued about 15minutes before the end of surgery.; CONDITION: Gynecopathy PRIMARY OUTCOME: The global score Quality of Recovery‐40 Scale(QoR‐40) at 24 hours after surgery); SECONDARY OUTCOME: Dosage of sedative analgesic drugs during operative;Acute pain score at immediately,6,12,and 24 hours after surgery;Dosage of postoperative analgesics;Consumption of vasoactive agents;postoperative nausea and vommiting score;duration of anesthesia and surgery;Awakening time; INCLUSION CRITERIA: 1.Age 18‐65 years ,2.ASA physical status I‐?,3.18.5=BMI=30,4.Schduled for laparoscopic surgery under general anesthesia,including laparoscopic total hysterectomy,myomectomy,double adnexectomy,and ovarian cyst removel(except for patients with malignant tumors),5.inforemed consent can be signed.

ChiCtr (2023). "Effect of myomectomy on pregnancy outcome of frozen embryo transfer cycle in infertile patients with FIGO 4-6 uterine fibroids: a multicenter randomized controlled clinical study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A:Perform hysteromyomectomy;Group B:Hysteromyomectomy not performed; CONDITION: FIGO 4‐6 uterine fibroids PRIMARY OUTCOME: live birth rate; SECONDARY OUTCOME: miscarriage rate;Ectopic pregnancy rate ;premature birth rate;clinical pregnancy rate;Cumulative live birth rate;Size changes of Uterine fibroid;Incidence of maternal complications during pregnanc;Incidence of neonatal complications;operative time;Complications of hysteromyomectomy;Cost of hysteromyomectomy;Cumulative clinical pregnancy rate; INCLUSION CRITERIA: 1. Aged 20 to 40 years; 2. Infertility patients planning to undergo IVF/ICSI; 3. MRI diagnosis shows that only single FIGO type 4‐6 fibroid with a diameter of 3‐7cm or combined no more than five FIGO type 4‐6 fibroids with a diameter of less than 2cm.

ChiCtr (2023). "The effect of N-acetylcysteine supplementation on ovulation induction in PCOS patients: a pragmatic, randomized, parallel-controlled, non-inferior study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: NAC group: During routine letrozole +uFSH ovulation stimulation, orally administrate NAC 1.8g/d daily (Usage: 0.6g, po, tid);Control group:Only routine letrozole +uFSH was administered to induce ovulation; CONDITION: polycystic ovarian syndrome PRIMARY OUTCOME: clinical pregnancy rate; SECONDARY OUTCOME: Ovulation rate per cycle;the incidence rate of OHSS;early pregnancy loss rate; INCLUSION CRITERIA: 1.the age of female partners were between 21 38 years old; 2. The cause of infertility in both spouses was diagnosed as ovulation disorder related to the woman's PCOS; 3. Previous ovulation induction treatment =2 cycles; 4. BMI=18.5, < 24. 5.. The semen examination of the male partner met the following requirements: semen volume =1.5ml, liquefaction time < 30min, concentration > 15×106/ml, PR=32%, NR+NP: =40%.

ChiCtr (2023). "Effect of perioperative esketamine bunching management on postoperative pain and gastrointestinal function of cervical cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control group:Normal saline was pumped,PCIA (sufentanil 3µ g/kg);Intervention group 1: Esketamine group1(Preoperative: 0.25 mg/kg, maintained at 0.15 mg · kg‐1 · h‐1, PCIA (sufentanil 2 µ g/kg+esketamine 1.5 mg/kg);Intervention group 2: Esketamine group2 ((Preoperative: 0.125mg/kg, maintained at 0.075 mg · kg‐1 · h‐1, PCIA (sufentanil 2 µ g/kg+Esketamine 0.75mg/kg)); CONDITION: Postoperative gastrointestinal dysfunction PRIMARY OUTCOME: The incidence of postoperative gastrointestinal dysfunction; SECONDARY OUTCOME: Daily I‐FEED score for 7 days after surgery;Daily visual analogue scale (VAS) rest and exercise scores, as well as number of analgesic pump presses, 7 days after surgery;;The dosage of opioid drugs and the dosage of esketamine;;Rehabilitation progress indicators: first exhaust, defecation time, first oral intake time, and first time out of bed activity time;;The incidence of respiratory depression, hypotension, vomiting, nausea, and itching within 24 and 48 hours after surgery.;The incidence of multiple dreams, nightmares, hallucinations, mental disorders, restlessness, difficulty in orientation, blurred vision, tachycardia, and salivation within 24 and 48 hours after surgery.; INCLUSION CRITERIA: ? Age 25‐65 ?American Society of Anesthesiologists grading I and II ?Body Mass Inde X18‐30kg/m2 ? Planned open surgery for cervical cancer patients under general anesthesia ? Surgical duration 2.5‐4.5 hours ? Patient is willing to use patient controlled intravenous analgesia ? Sign informed consent form

ChiCtr (2023). "Effect of phospropofol disodium and sevoflurane anesthesia on immune cell expression profiling in gynecologic malignancy surgery: a prospective, double-blind, randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Phosphopofol disodium group:Midazolam 0.2 mg, fopropofol disodium 20‐30 mg/kg, sufentanil 0.2‐0.4 µg/kg, cis‐atracurium 0.2 mg/kg intravenously in the fopropofol disodium group, and the patient's jaw was relaxed and inserted into the endotracheal tube through the mouth. ;Sevoflurane group:Under the monitoring of BIS, the sevoflurane group inhaled 8% sevoflurane by tidal volume, causing the patient's consciousness to disappear, adjusted the concentration of inhaled sevoflurane to 3 4% and reduced the fresh air flow to 2 3L/min, and maintained the BIS value between 45 55. Sufentanil 0.2 to 0.4 micrograms/kg was injected intravenously, cis‐atracurium 0.2 mg/kg, and the patient's jaw was relaxed and inserted into the endotracheal tube through the mouth.; CONDITION: Gynecological malignant tumors PRIMARY OUTCOME: Levels of circulating natural killer T cells, type 1 and type 17 helper T cells, and cytotoxic T cells in peripheral venous blood.; SECONDARY OUTCOME: The proportion of CD4 and CD25 expression in circulating regulatory T cells, and the proportion of circulating neutrophils, lymphocytes, and monocytes; INCLUSION CRITERIA: 1. Age greater than 20 years old and less than 70 years old 2. Surgical surgery for gynecological malignant tumors (cervical cancer, ovarian cancer and endometrial cancer) under general anesthesia 3. ASA grade I. III 4. Sign the informed consent form

ChiCtr (2023). "Effect of target-controlled infusion of remazolam on postoperative quality of patients with gynecologic malignant tumor after laparoscopic surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group P:Propofol;Group R:Remazolam; CONDITION: gynecologic malignant tumor PRIMARY OUTCOME: Qor‐15 score; SECONDARY OUTCOME: Intraoperative vital signs;Partial pressure of end‐respiratory carbon dioxide;Frequency of use of vasoactive drugs;Incidence of adverse events in the anesthesia recovery room;The dwell time of the PACU;Recovery time;Extubation time;Length of hospital stay; INCLUSION CRITERIA: ?Age 18‐65 years ?the American Society of Anesthesiologists (ASA) grade I‐II Grade ? was able to conduct the Recovery Quality Rating Questionnaire

ChiCtr (2023). "Effect of time-restricted feeding in combination with short -cating oral contraceptives on PCOS: a prospective randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group (Group TRF):Subjects in the TRF group were instructed to adhere to a strict 8 hour time‐restricted eating for 12 weeks, while also regularly taking drospirenone and ethinylestradiol II. ;Control group (Group COC):Regularly taking drospirenone and ethinylestradiol II for 12 weeks; CONDITION: Polycystic Ovary Syndrome PRIMARY OUTCOME: Spontaneous ovulation; SECONDARY OUTCOME: Serum glucose;Serum insulin;Triglyceride;Cholesterol;High‐density lipoprotein;Low‐density lipoprotein;Estradiol;Progesterone;Follicle stimulating hormone;Luteinizing hormone;Total testosterone;Prolactin;Uric Acid;Creatinine;Weight;Waist‐hip ratio; INCLUSION CRITERIA: [1] Female aged 18‐45 [2] Women diagnosed with PCOS according to Rotterdam criteria [3] Sign the informed consent voluntarily and be willing to participate in this study

ChiCtr (2023). "Effect of ultrasound-guided stellate ganglion block on postoperative pain, nausea and vomiting in patients undergoing gynecological laparoscopic surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group S:Stellate ganglion block;Group C:control group; CONDITION: Laparoscopic gynecological surgery PRIMARY OUTCOME: Postoperative pain;Postoperative nausea and vomiting; SECONDARY OUTCOME: MAP, HR, SP02, BIS;Intraoperative anesthetic dosage, intraoperative volume, operation time, recovery time, extubation time, Richimond restlessness and sedation score after recovery, PACU stay time, alderete score before returning to the ward;Postoperative hospital stay and EQ‐5D were used to evaluate the quality of early recovery, sleep quality before and after surgery, pain threshold, anxiety and depression scores were determined by Von Frey fiber.;Postoperative time of getting out of bed, feeding time, exhaust time, discharge time, surgery‐related complications, MMSE scale score; INCLUSION CRITERIA: 1. Gynecological laparoscopic surgery patients (including laparoscopic uterine surgery, laparoscopic adnexal surgery, laparoscopic myomectomy, fallopian tube plastic surgery, etc.); 2. Age >=18 years; 3.BMI < 18.5‐30 kg/m^2; 4. ASA I III level.

ChiCtr (2023). "The effect of Vitamin D3 supplementation on ovulation induction in PCOS patients: a pragmatic, randomized, parallel-controlled, non-inferior study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Vitamin D supplementation group:During routine letrozole +uFSH ovulation stimulation, 4000IU of vitamin D is taken orally daily ;Control group:Only routine letrozole +uFSH was administered to induce ovulation; CONDITION: polycystic ovarian syndrome PRIMARY OUTCOME: clinical pregnancy rate; SECONDARY OUTCOME: Ovulation rate per cycle;the incidence of OHSS;early pregnancy loss rate; INCLUSION CRITERIA: 1.the age of female partners were between 21 38 years old; 2. The cause of infertility in both spouses was diagnosed as ovulation disorder related to the woman's PCOS; 3. Previous ovulation induction treatment =2 cycles; 4. BMI=18.5, < 24; 5. Vitamin D deficiency (serum vitamin D less than 20ng/ml).

ChiCtr (2023). "Effect of vitamin D supplementation on the clinical outcome of assisted reproductive technology in infertile patients with endometriosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: experimental group:Oral vitamin D;control group:None; CONDITION: Endometriosis PRIMARY OUTCOME: Carbohydrate antigen CA‐125;Serum vitamin D levels;B ultrasound;Clinical pregnancy rate;Biochemical pregnancy rate;Cytokines; SECONDARY OUTCOME: Height;Weight;Reactive oxygen species;Malondialdehyde, MDA;Glutathione peroxidase, GSH‐PX;Superoxide dismutase, SOD; INCLUSION CRITERIA: 1. Aged 20‐40 years; 2. A patient with endotropism diagnosed laparoscopically.

ChiCtr (2023). "The effectiveness, safety and health economic evaluation of progestogen treatment for endometrial hyperplasia without atypia: a prospective randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group of therapeutic intervention:Levonorgestrel‐releasing intrauterine system;Controlled group of therapeutic intervention:Dydrogesterone;Experimental group of preventive intervention:Levonorgestrel‐releasing intrauterine system;Controlled group of preventive intervention:Dydrogesterone; CONDITION: Endometrial hyperplasia (EH) PRIMARY OUTCOME: Complete remission rate after 6 months treatement; SECONDARY OUTCOME: Recurrence rate of patient who achieved complete remission;The total costs of treatment and follow‐up; INCLUSION CRITERIA: 1. Premenopausal female between 30‐50 years old. 2. Patients with pathological diagnosis of endometrial hyperplasia. 3. Willing to receive progestogen treatment. 4. Without previous diagnosis of EH. 5. Patients should return for regular follow‐up and pathological examinations. 6. Patients should sign the informed consent before inclusion.

ChiCtr (2023). "Effects Analysis of HIFU Combined with Dienogest in the Treatment of Adenomyosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control Group:Oral dienogest, once daily, one capsule each time for 6 month;Experimental Group:HIFU treatment, oral dienogest the next day after HIFU, once daily, one capsule each time for 6 month; CONDITION: Adnomyosis PRIMARY OUTCOME: Uterine volume; SECONDARY OUTCOME: Visual Analogue Scale ;carbohydrate antigen 125 (CA125); INCLUSION CRITERIA: Women of childbearing age, 25‐50 years old; Adenomyosis was diagnosed according to clinical symptoms, gynecological B‐ultrasound or pelvic plain scan + enhanced magnetic resonance imaging (MRI) ; Willing to receive high‐intensity focused ultrasound therapy or oral dienogest therapy; All patients and their family members were informed of the study and signed informed consent voluntarily.

ChiCtr (2023). "Effects of Lactobacillus acidophilus on insulin resistance in obese patients with polycystic ovary syndrome: a randomized controlled clinical study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:Lactobacillus acidophilus‐JYLA‐191+melbine (DMBG);Control group:Melbine (DMBG); CONDITION: 5A80.1 Polycystic ovarian syndrome PRIMARY OUTCOME: Insulin resistance;Six items of sexual hormones; SECONDARY OUTCOME: Liver function;Menstrual cycle;Height and weight; INCLUSION CRITERIA: (1)Patients with PCOS with obesity (BMI=28kg/?) and insulin resistance inde X(HOMA‐IR) greater than or equal to 2.69 (2)Women of childbearing age, aged 18‐40 years (3)No drugs affecting menstruation (such as contraceptives, hormones or other drugs affecting insulin, blood sugar, se Xhormones and lipid metabolism) were taken within 3 months, and no related treatment was used, and no induced abortion was recorded; (4) Gynecological examination and auxiliary examination: there are no organic lesions in the internal and external genitalia, and there are no other primary diseases; (5) Those who have signed an informed consent form.

ChiCtr (2023). "Effects of perioperative oxycodone as the sole opioid on immune function in patients undergoing gynecologic malignancy surgery based on multimodal analgesia." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group O:During anesthesia induction, oxycodone 0.3 mg/kg was injected intravenously.Intraoperative injection of oxycodone 0.03 mg/kg on demand to maintain analgesia;Postoperative PCIA: Oxycodone 50 mg diluted to 100 ml;Group C:During anesthesia induction, sufentanil was injected 0.3 µg/kg;Intraoperative continuous infusion of remifentanil 0.1‐0.3 µg/kg/min to maintain analgesia;Postoperative PCIA: Sufentanil 50 µg diluted to 100 ml; CONDITION: patients undergoing gynecologic malignancy surgery PRIMARY OUTCOME: CD4+/CD8+ at 24 hours after surgery; SECONDARY OUTCOME: Degree of pain scored by visual analogue scale (VAS);Catheter‐related bladder discomfort; INCLUSION CRITERIA: aged 18 to 64 years, American Society of Anesthesiologists (ASA) grade =?, scheduled for laparoscopic gynecological malignancy surgery under general anesthesia.

ChiCtr (2023). "Efficacy and safety of minocycline versus doxycycline in the treatment of chronic endometritis: a single-center, randomized, open-label, non-inferiority trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group and control group:Oral doxycycline;Experimental group and control group:Oral minocycline; CONDITION: chronic endometritis PRIMARY OUTCOME: Immunohistochemical examination of endometrial tissue shows a negative conversion rate of CD138+cells; SECONDARY OUTCOME: Immunohistochemical examination of endometrial tissue shows a negative conversion rate of CD56/57+cells;TBNK lymphocytes;Th1 and Th2 cytokines;live birth rate; INCLUSION CRITERIA: ? Premenopausal women who still need to have children; ?CD138 immunohistochemical staining showed more than 1 plasma cell per 10HPF. ? No endometrial hyperplasia or malignant or structural pathological features of the uterus; (4) Consent to perform a second endometrial biopsy approximately 4 to 6 weeks after the first endometrial biopsy; ? Obtain informed consent from patients and their families, and sign informed consent.

ChiCtr (2023). "Efficacy and Safety of Recombinant Human Granulocyte Colony-Stimulating Factor in Patients with Unexplained Recurrent Pregnancy Loss: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:rhG‐CSF+aspirin+progesterone;Control group:placebo+aspirin+progesterone; CONDITION: unexplained recurrent pregnancy loss PRIMARY OUTCOME: 24 weeks live birth rate; SECONDARY OUTCOME: early pregnancy loss rate;clinically confirmed pregnancy rate;ongoing pregnancy rate(to 10 weeks);ongoing pregnancy rate(to 12 weeks);28 weeks live birth rate;ectopic pregnancy rate;stillbirth rate;incidence rate of pregnancy complications;neonatal weigh;neonatal Apgar score;neonatal birth defect rate;incidence rate of adverse effect; INCLUSION CRITERIA: (1)Age of 20 to 37 years old (the reason for setting the upper age limit of 37 years old is that abortion caused by chromosomal aberrations has a higher incidence in advanced maternal age, and cannot be prevented by immunological regulation);(2)Body mass inde X(BMI) between 15 to 29 at screening(Mean±SD of out‐patients from two centers in the past 2 years);(3)Menstrual cycle within 21‐35 days,and the difference between the longest cycle and the shortest cycle only in 1 year is no more than 7 days;(4)History of recurrent pregnancy loss, defined as two or more fetal losses before 24 weeks of gestation (including biochemical pregnancy);(5)Willingness to conceive spontaneously and signing of informed consent form.

ChiCtr (2023). "Efficacy and safety of vitamin D supplementation in the treatment of pediatric overactive bladder syndrome: a prospective, randomized, controlled, single-center clinical study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Vitamin D supplementation group:Supplementation with oral vitamin D preparations;Tolterodine group:Take tolterodine;Standard urotherapy group:Dietary instruction, behavioral training, bladder training; CONDITION: Overactive Bladder Syndrome PRIMARY OUTCOME: pediatric lower urinary tract symptom score;Overall symptom improvement score;bladder diary;Urinary frequency, urinary urgency, urinary incontinence, maximum urinary output;Maximum urinary urgency score;urinary urgency score;Drug‐related adverse reactions;Serum vitamin D levels; INCLUSION CRITERIA: (1) Children older than 4 years of age with a diagnosis of OAB seen at the outpatient urology clinic of the Children's Hospital of Chongqing Medical University (diagnosis follows the latest ICCS recommendations). (2) Children with a serum vitamin D level of less than 35 ng/ml as indicated by the laboratory results of our hospital. (3) The child's guardian has been informed of the nature of the study, understands the provisions in the protocol, can ensure compliance, and has signed an informed consent form.

ChiCtr (2023). "Efficacy of polyethylene glycol recombinant human growth hormone on pregnancy outcomes for patients with thin endometrium undergoing frozen embryo transfer: a pilot study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:Pretreatment with long‐acting growth hormone before FET;Control group:Routine HRT+FET; CONDITION: Thin endometrium PRIMARY OUTCOME: Ongoing pregnancy rate; SECONDARY OUTCOME: Chemical pregnancy rate;Clinical pregnancy rate;Pregnancy loss rate;Ectopic pregnancy rate;Endometrial Thickness on progestogen initiate day;Endometrial morphology on progestogen initiate day;Endometrial blood flow indicators on progestogen initiate day; INCLUSION CRITERIA: (1) Females aged 20‐39; (2) Endometrial thickness<7 mm in trigger day of conventional ovulation protocol or progestogen conversion day 2 or more times previously; (3) BMI: 18‐30kg/m2 (included); (4) patients who will planing to perform freeze‐thaw single blastocyst transplantation (including IVF, ICSI, and PGT‐A cycles); (5) At least 1 blastocyst in IVF/ICSI cycles or at least 1 euploid embryo in PGT‐A cycles left for transfer, with a Gardner morphological score of = 4BC (D5 or D6); (6) Be capable of giving informed consent.

ChiCtr (2023). "Erzhitiangui granule in improving the outcomes of IVF/ICSI-ET in elderly patients with DOR: a prospective randomized, controlled, double-blind trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental Group:Erzhitiangui‐Decoction;Control Group:placebo; CONDITION: diminished ovarian reserve PRIMARY OUTCOME: Cumulative clinical pregnancy rate; SECONDARY OUTCOME: TCM syndrome score of kidney Yin deficiency syndrome;Serum E2 and P4 levels on trigger day;2PN fertilization number;Number of embryos available; INCLUSION CRITERIA: ? Meet the diagnostic criteria of diminished ovarian reserve: AFC=5 or AMH=1.2ng/ml; ? Conforming to the syndrome differentiation standard of kidney Yin deficiency syndrome of TCM; ? Age of 35‐42 years old; ? Sign the informed consent.

ChiCtr (2023). "Evidence-based study and clinical application of aromatherapy on postpartum depression/anxiety." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: experimental group:Inhalation with sweet orange essential oil;control group:Inhalation with jojoba oil; CONDITION: Postpartum Depression PRIMARY OUTCOME: postpartum depression;postpartum anxiety;serum estradiol;Serum 5‐hydroxytryptamine; SECONDARY OUTCOME: Postpartum sleep quality; INCLUSION CRITERIA: 1. Aged >= 18 years; 2. Edinburgh Postnatal Depression score >= 9 or State‐Trait Anxiety Inventory > 40; 3. Singleton full‐term delivery; 4. Cooperate with the examination, understand and agree to the study.

ChiCtr (2023). "An exploratory clinical trial on the efficacy and safety of recombinant human follicle stimulating hormone+recombinant luteinizing hormone (r-hFSH+r-hLH) in young patients with diminished ovarian reserve (DOR) (POSEIDON Group 3)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group A:From the 3rd day of menstrual cycle, a fixed dose of r‐hFSH 300IU (Gonal‐F, product of Merck, Germany)+r‐hLH 150IU (Luveris, product of Merck, Germany) was injected for ovarian stimulation.;Group B:From the 3rd day of menstrual cycle, a fixed dose of r‐hFSH 300IU (Gonal‐F, a product of Merck, Germany) was injected for ovarian stimulation.; CONDITION: Infertility PRIMARY OUTCOME: Ongoing pregnancy rate; SECONDARY OUTCOME: Follicular Output Rate;Follicle‐To‐Oocyte Index;fertilization rate;implantation rate;Biochemical pregnancy rate;Clinical pregnancy rate;Live birth rate;Number of oocytes retrieved;number of MII oocytes;Number of transferrable embryos;Number of high‐quality embryos;Number of fresh embryo transfers;Serum LH?estradiol and progesterone Level on HCG Day;Endometrial thickness on embryo transfer day;pregnancy loss;ectopic pregnancy;pregnancy complications; INCLUSION CRITERIA: Subjects meeting Poseidon Group 3 criteria: (1) Age < 35 years old; (2)AFC < 5 or AMH < 1.2 µg /L

ChiCtr (2023). "Explore the mechanism of acupuncture intervention on metabolism and reproductive function of PCOS-IR patients based on ß-endorphin-insulin pathway." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group:Basic treatment+metformin;treatment group:Basic treatment + acupuncture; CONDITION: 5A80.1 Polycystic Ovary Syndrome PRIMARY OUTCOME: Detection of sex hormones and related indexes of glucose and lipid metabolism;pregnancy rate, abortion rate; SECONDARY OUTCOME: Follicle development was monitored by ultrasound;Detection of ß‐endorphin, gonadotropin releasing hormone and insulin signaling factor; INCLUSION CRITERIA: 1.The diagnostic criteria for both PCOS and insulin resistance were met; 2. Between 20 and 40 years old; 3. Voluntary signing of informed consent.

ChiCtr (2023). "-Hybrid effectiveness-implementation of task-sharing in prevention of rural perinatal depression: a cluster randomized trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: intervention group:Task‐sharing App‐based Intervention ;Control group:Self‐help App‐based Intervention; CONDITION: perinatal depression PRIMARY OUTCOME: depressive status;negative emotion symptom;sleep quality;parenting competence;social support;reach;adoption;implementation;maintenance; SECONDARY OUTCOME: barriers and facilitators of implementation; INCLUSION CRITERIA: 1) = 18 years old; 2) have established a pregnancy health care record at township health centers; 3) 6‐13 weeks of pregnancy; 4) Edinburgh Postnatal Depression Scale: EPDS < 13; 5) informed consent.

ChiCtr (2023). "An Intervention Reminder Model for Female Stress Urinary Incontinence: a Multi-centered, Random Controlled Clinical Study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group with assistance reminder:daily reminder from smartphone APP;Control group:general education; CONDITION: Stress urinary incontinence PRIMARY OUTCOME: modified Oxford Grading Scale;1h pad test;Glazer assessment; SECONDARY OUTCOME: IIQ‐7;SF‐12;I‐QOL;PISQ‐12; INCLUSION CRITERIA: 1) Adult female, normal cognition, primary school education/academic ability, can use mobile phones; 2) symptoms consistent with stress urinary incontinence; 3) Voluntarily participate in this trial and give written informed consent.

ChiCtr (2023). "A multicenter clinical study on floating needle pre intervention for primary dysmenorrhea in young women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment group:Floating needle pre intervention;Waiting for the backup group:Maintain original lifestyle habits without intervention; CONDITION: Primary dysmenorrhea PRIMARY OUTCOME: Response rate to VAS score decrease in dysmenorrhea after treatment (3rd menstrual cycle) (proportion of patients with VAS score decrease of 50% or VAS score decrease of = 3 points); SECONDARY OUTCOME: 1. Response rate of dysmenorrhea relief during menstrual cycles 1,2, 4, 5, and 6;VAS score at peak pain intensity per cycle;Duration of dysmenorrhea per cycle (cumulative, degree, h);CO XMenstrual Symptom Scale (CMSS);Beck Anxiety Scale, Beck Depression Scale;The demand for painkillers;Patient self‐evaluation;Adverse event occurrence rate; INCLUSION CRITERIA: (1) Women aged 18 to 30 who have not given birth; (2) Conforming to PD diagnostic criteria: spasmodic pain in the lower abdomen that occurs before or during menstruation without other diseases such as endometriosis; (3) The basic pattern of the cycle is (28 ± 7) d; (4) The visual analogue scale (VAS) score for pain in at least three consecutive menstrual cycles is = 40mm.

ChiCtr (2023). "A multicenter randomized controlled study about Levonorgestrel-releasing intrauterine device suture in the treatment of adenomyosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: LNG‐IUS suture fixation:Hysteroscopic fixation of Manyule ring;simple placement of LNG‐IUS:Simple Manyue Music Ring Placement; CONDITION: adenomyosis PRIMARY OUTCOME: LNG‐IUS expulsion rate; SECONDARY OUTCOME: algomenorrhea;Menstrual volume;side effects;CA125; INCLUSION CRITERIA: 1:She had menorrhagia or dysmenorrhea and met the diagnosis of "adenomyosis"; 2:She had a strong desire to preserve the uterus; 3:She had no fertility requirements in the short term.

ChiCtr (2023). "A multi-center randomized controlled trial study on the effects of Tiepi Fengdou Granules on nutrition and menopausal-related symptoms in menopausal women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control group:Bujiale 1mg + Dydrogesterone 5mg/day, continuous administration for 90 days;Experimental group 1:Tiepi Fengdou Granules (3g/pack), 2 packs/time, 3 times a day, for 90 days;Experimental group 2:Tiepi Fengdou Granules (3g/pack), 2 packs/time, 3 times a day, combined with Bujiale 1mg + Dydrogesterone 5mg/day, taken continuously for 90 days; CONDITION: menopausal syndrome PRIMARY OUTCOME: Sex hormone test;Liver and kidney function tests;Thyroid function test;Ultrasound of uterus and breast;Vaginal microecology examination; INCLUSION CRITERIA: 1. Female aged 40‐65 years old; 2. Menopause for more than 12 months and pregnancy excluded, follicle‐stimulating hormone >40U/L and estradiol <10‐20pg/ml; 3. Have a uterus and at least one ovary; 4. Accompanied by vasomotor symptoms such as hot flashes or symptoms of autonomic nervous system dysfunction such as palpitations, dizziness, headache, insomnia, tinnitus, or psychiatric and neurological symptoms such as agitation, anxiety, low mood, depression, or vaginal dryness, dyspareunia, Women with recurrent vaginal infections, difficulty urinating, frequent urination, urgency and other urogenital symptoms, or osteoporosis; 5. Voluntarily participate and sign the consent form to enter clinical research.

ChiCtr (2023). "Multicenter study of the safety and efficacy of ultrasound-guided aspiration and sclerotherapy with polidocanol for benign ovarian cyst." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Test group:Polidocanol injection;Control group:Lauromacrogol injection; CONDITION: Endometriosis PRIMARY OUTCOME: Reduction rate of cyst volume; SECONDARY OUTCOME: Cyst recurrence rate;Visual analogue scales;Quality of life;Medical costs;Duration of sclerotherapy;Total amount of sclerosing agents; INCLUSION CRITERIA: 1. At least 18 years old; 2. According to the comprehensive judgment of clinical, imaging and laboratory examination, it was diagnosed as ovarian endometriosis with a diameter of 4‐10 cm; 3. Ultrasonography revealed a single cyst in one or both ovaries with unspaced unilocular cysts; 4. Serum carbohydrate antigen 125 (CA‐125) < 200 U/mL; 5. No hormones and gonadotropin‐releasing hormone analogues (GnRH‐a) were taken in the past three months; 6. No other gynecological diseases, serious heart and lung diseases; 7. For females of childbearing potential, pregnancy test results were negative at screening/baseline; 8. Sign informed consent voluntarily and follow protocol requirements.

ChiCtr (2023). "A multi-center, randomized, double-blind and positive parallel control clinical study of the efficacy and safety of Levornidazole Disodium Phosphate for Injection in the treatment of pelvic anaerobic infections." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Test Group 1:Levornidazole Disodium Phosphate for Injection, intravenous drip, each 1g (4 tubes) of the test drug will bedissolved in 100mL of 0.9% sodium chloride injection. The first daily administration of the test drug is given once a day, 2 g each time, a total of 200 mL; the second administration is given with 100mL of 0.9% sodium chloride injection, each bottle drip time of 30‐60 minutes, continuous administration for 7 days, each two infusions interval of 12 hours. (q24h Dosing group);Test Group 2:Levornidazole Disodium Phosphate for Injection, intravenous drip, dissolved in 100mL of 0.9% sodium chloride injection per 1g (4 tubes) of the test drug. The first daily administration of the test drug is given once a day, that is, 1g (dissolved in 100mL of 0.9% sodium chloride injection), the additional 100mL of 0.9% sodium chloride injection is given once; the second administration of 4 vials (dissolved in 100mL of 0.9% sodium chloride injection), each bottle drip time of 30‐60 minutes, continuous administration for 7 days, each two infusions interval of 12 h. (q12h, dosing group);Control group:Levornidazole and Sodium Chloride Injection, intravenous drip, the first daily administration of 0.5g (100mL) is given, and another 100mL of 0.9% sodium chloride injection is given once to make the total liquid volume of each administration reach 200mL; the second administration is given 0.5 g (100 mL) with a drip time of 30‐60 minutes per vial for 7 consecutive days with an interval of 12 hours.; CONDITION: Gynecological pelvic inflammatory diseases (including endometritis, salpingitis, salpingo‐oophoritis, tubo‐ovarian abscess, pelvic peritonitis, parauterine connective tissue inflammation and others) PRIMARY OUTCOME: Clinical efficacy after 14 days of treatment; SECONDARY OUTCOME: Microbiological efficacy and comprehensive efficacy after 14 days of treatment;Clinical efficacy, microbiological efficacy, and comprehensive efficacy of 7‐day treatment; INCLUSION CRITERIA: 1)Female patients aged 18 to 65 (including patients aged 18 and 65); 2)Participants have not used effective anti‐anaerobic drugs 72 hours before enrollment 3)Patients with gynecological pelvic infections caused by anaerobic bacteria that the investigators believe need to be treated with injection: sexually active women and STI (sexually transmitted infections) patients who meet the following conditions and have no other causes: a) uterine tenderness or adnexal tenderness or cervical motion tenderness; b) At least one of the following additional conditions is met: body temperature (axillary temperature) = 37.8°C, purulent cervical or vaginal discharge, leukocytosis detected by microscopic examination of vaginal discharge (15 per high‐power white blood cell count =), Complete Blood Count white blood cell count = 10X10^9/L; C‐reactive protein is elevated. 4) The subjects volunteered to be tested and signed the informed consent form, and the process of si

ChiCtr (2023). "A multi-center, randomized, double-blind, placebo-controlled phase II clinical trial to evaluate the efficacy and safety of vaginal use of quadruple Live Lactobacillus capsule in the treatment of postmenopausal atrophic vaginitis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:Lactobacillus quad live capsule in vaginal use;Control group:placebo; CONDITION: postmenopausal atrophic vaginitis PRIMARY OUTCOME: vaginal microecology; SECONDARY OUTCOME: TCT (lateral vaginal wall);subjective symptoms;Vaginal sign score; INCLUSION CRITERIA: 1. Sign the informed consent voluntarily, and be able to follow the requirements of the program procedures; 2. Women with a sexual history, aged =45 years and =70 years at the time of informed consent; 3. At the time of screening, the chief complaint was natural menopause =12 months or medical records showed bilateral ovariectomy =6 months, or follicle‐stimulating hormone (FSH) =40 IU/L and estradiol (E2) =20 pg/mL. 4. Moderate to severe vaginal dryness, or moderate to severe dyspareunia for sexually active persons (stable partners and having or attempting to have vaginal intercourse =1 times per month) within 3 months before screening; Note: Vaginal dryness: moderate, most of the time feel vaginal dryness and discomfort, but does not affect daily life; Severe, has been feeling vaginal dryness discomfort, affecting daily life. Pain during intercourse: moderate, most of the time there is pain during intercourse, intercourse brings little satisfaction

ChiCtr (2023). "A Multicenter, Randomized, Investigator-Blind, Positive Parallel-Controlled Phase III Clinical Study to Evaluate the Efficacy of Recombinant Human Follicle-Stimulating Hormone Injection (LZ-B-01) and Gonal-f in Controlled Ovarian Hyperstimulation in Assisted Reproductive Technology." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:Recombinant Human Follicle‐Stimulating Hormone Injection;Control group:Gonal‐f; CONDITION: 1.Women with anovulation (including polycystic ovary syndrome [PCOS]) who are unresponsive to clomiphene citrate treatment. 2.Women undergoing controlled ovarian hyperstimulation in assisted reproductive technology (ART) such as in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and zygote intrafallopian transfer (ZIFT) to stimulate the development of multiple follicles. Patients with severe deficiency of luteinizing hormone (LH) and follicle‐stimulating hormone (FSH). PRIMARY OUTCOME: Compare the number of oocytes retrieved in two groups. Note: Follicles with a diameter =10 mm must be punctured. Total oocyte count: Defined as the average number of oocytes obtained per subject 36±2 hours after trigger administration.; SECONDARY OUTCOME: Total dosage of experimental drug;Duration of experimental drug stimulation in the trial (number of days);Hormone levels (LH, E2, P) and their changes after experimental drug administration in the trial.;Serum E2 level on the trigger day;The levels and changes of hormones [luteinizing hormone (LH), estradiol (E2), progesterone (P) measured in the central laboratory] after administration of experimental drugs;The percentage of follicles with a diameter =10mm on the 6th day of ovarian stimulation (number of follicles with a diameter =10mm divided by the total number of follicles).;The percentage of follicles with a diameter =14mm on trigger day (number of follicles with a diameter =14mm divided by the total number of follicles).;The proportion of MII (metaphase II) oocytes to the total number of oocytes retrieved on the day of egg retrieval, specifically for intracytoplasmic sperm injection (ICSI) only.;The normal fertilization rate refers to the percentage of embryos showing both pronuclei (PN) and polar bodies (PB) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).;The usable embryo rate on the 3rd day after egg retrieval ;The embryo transfer rate (on the 3rd to 5th day after egg retrieval);The serum hCG/ß‐hCG positive rate (12‐14 days after embryo transfer);The clinical pregnancy rate (4‐7 weeks after embryo transfer) ; INCLUSION CRITERIA: In order to be eligible for participation in this study, subjects must meet all of the following INCLUSION CRITERIA: 1)Couples voluntarily participating in the clinical trial, meeting the requirements of relevant national regulations for assisted reproductive technology, and signing an informed consent form (ICF). 2)Female infertility patients aged 20 to 38 years (including the boundary values). 3)Regular natural menstrual cycles within the range of 24 to 35 days (including the boundary values). 4)Body mass inde X(BMI), calculated as BMI = weight (kg)/height^2 (m^2), within the range of 18.5 to 28.0 kg/m^2 (including the boundary values). 5)Diagnosed with tubal infertility, unexplained infertility, or male factor infertility in females. 6)The examination results conducted within the 60 days prior to randomization confirmed the following: a.Serum levels of follicle‐stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (

ChiCtr (2023). "Nintedanib in Prevention of Pulmonary Fibrosis in Malignant Ovarian Germ Cell Tumor Patients Receiving Bleomycin: a randomized, double-blind, controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: nintedanib group (experimental group):standard BEP regimen chemotherapy with nintedanib 150mg bid po till the end of treatment;placebo group (control group):standard BEP regimen chemotherapy with plabeco 150mg bid po till the end of treatment; CONDITION: Malignant Ovarian Germ Cell Tumor PRIMARY OUTCOME: Absolute decline value in forced vital capacity (ml);Percent decline in predicted forced vital capacity (ml);Carbon monoxide dispersion (DLCO) decline rate (%); SECONDARY OUTCOME: The safety and adverse effects of nintedanib in the treatment of malignant ovarian germ cell tumors;Onlogical outcomes of patients between two groups;Fertility outcomes of patients between two groups;Quality of life patients between two groups; INCLUSION CRITERIA: 1. Women with malignant germ cell tumor and patients treated with chemotherapy regimen containing bleomycin; 2. Aged >= 14 years; 3. Can complete lung function examination; 4. FVC is greater than 45% of the normal predicted value and DLCO is greater than 60% of the normal predicted value; 5. Informed consent and signed informed consent; 6. Good compliance.

ChiCtr (2023). "NOX index guidied administration of remifentanil in gynecological laparoscopic surgery: a randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:Nox‐guided remifentanil in laparoscopic surgery:;standard of care:Remifentanil was used according to clinical experience; CONDITION: gynecological laparoscopic surgery PRIMARY OUTCOME: The consumption of remifentanil during the surgery; SECONDARY OUTCOME: The number of patients with hemodynamic instability;Plasma ACTH and serum cortisol concentrations before anesthesia induction, at the end of suture, at extubation, and after leaving PACU; INCLUSION CRITERIA: (1) Age above 18 and below 65 (2)ASA grade I to III (3) Patients undergoing elective laparoscopic adnexal and (or) hysterectomy procedures (4) Expected operation duration > 1 hour (5) Sign informed consent

ChiCtr (2023). "Pregnancy outcomes following a letrozole ovulation induction cycle vs. a hormone replacement cycle with GnRH-a pretreatment for frozen-thawed embryo transfer in women with endometriosis: a randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: LE :letrozole ovulation induction protocol for frozen‐thawed embryo transfer;GnRH‐a+HRT:hormone replacement therapy with GnRH‐a pretreatment protocol for frozen‐thawed embryo transfer; CONDITION: Infertility PRIMARY OUTCOME: Live birth rate; SECONDARY OUTCOME: Clinical pregnancy rate;Biochemical pregnancy rate;miscarriage rate;Incidence of obstetric and perinatal complications;Incidence of neonatal complications; INCLUSION CRITERIA: 1. Age between 20 and 40 years; 2. Patients diagnosed with endometriosis by laparoscopy or laparotomy, or meeting all of the following criteria: (1) Cyclical and non‐cyclical signs and symptoms (dysmenorrhea, dyspareunia, dyschezia, etc.) (2) Palpable nodularities in the pouch of Douglas found on bimanual pelvic examination (3) Endometrioma found by TVS 3. Previous embryo transfer failure cycle is = 2, and previous ovulation cycle is = 2; 4. Performing frozen‐thawed single blastocyst transfer, and the blastocyst was morphologically graded as 4BC or better using Gardner grading criteria.

ChiCtr (2023). "pre-menstrual acupuncture at sensitized points in the treatment of primary dysmenorrhea: a randomized controlled trail." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: acupuncture group:acupuncture;Ibuprofen sustained‐release capsules can be taken when abdominal pain is unbearable (VAS=7) in both groups.;blank control group:follow up;Ibuprofen sustained‐release capsules can be taken when abdominal pain is unbearable (VAS=7) in both groups.; CONDITION: primary dysmenorrhea PRIMARY OUTCOME: menstrual pain visual analogue scale score;Incidence of dysmenorrhea; SECONDARY OUTCOME: symptom duration and severity measured by the Co XMenstrual Symptom Scale, CMSS;Usage of ibuprofen during menstruation; INCLUSION CRITERIA: A ) The diagnostic criteria were in line with the ' 2017 SOGC clinical practice guidelines : primary dysmenorrhea ( No.345 ) ' and the diagnostic criteria for primary dysmenorrhea in the 9th edition of the textbook ' Obstetrics and Gynecology ' of People 's Health Publishing House ( Xie Xing, Kong Beihua, Duan Tao ) ; tCM syndrome differentiation is based on ' evidence‐based acupuncture clinical practice guidelines‐primary dysmenorrhea ', which is differentiated as qi stagnation and blood stasis syndrome. b ) 18‐30 years of age ; c ) The course of disease was more than 6 menstrual cycles, and the average VAS pain score was = 4 points for 3 consecutive months ; d ) No other treatment was taken or combined within 2 weeks before enrollment ; e ) Regular menstrual cycle, cycle in 28 ± 7 days ; ( f ) To sign the informed consent.

ChiCtr (2023). "A prospective, randomized, controlled, and multicenter clinical study on Shenluo Tiaojing pills and Shenluo Yuchun pills in treatment of polycystic ovary syndrome of kidney-yang deficiency and phlegm obstruction type and kidney-yin deficiency and phlegm-blood stasis type." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment group (Kidney‐yang deficiency and phlegm obstruction type):Shenluo Tiaojing pills 12 g/dose, twice daily, taken with warm water at half an hour after meal for 6 months in total ;Control group (Kidney‐yang deficiency and phlegm obstruction type):Drospirenone and ethinylestradioltablets, from the fifth day of menstruation, one tablet at the same time every day for 21 consecutive days;Treatment group (Kidney‐yin deficiency and phlegm‐stasis type):Shenluo Yunchun pills 15 g/dose, twice daily, taken with warm water at half an hour after meal for 6 months in total ;Control group (Kidney‐yin deficiency and phlegm‐stasis type):Metformin hydrochloride tablets, taken orally with meals starting from the first day of menstruation, 500mg/dose, three times a day, for 6 cycles in total; CONDITION: Polycystic Ovary Syndrome PRIMARY OUTCOME: Basal Body Temperature;Ultrasound follicle monitoring; SECONDARY OUTCOME: BMI;WHR;Acne score;Melanosis (pseudoacanthosis nigricans) score;Determination of sexual hormone levels;OGTT;Insulin release test;Blood lipid; INCLUSION CRITERIA: 1) Patients aged 16 40 (included); 2) Those conforming to PCOS diagnostic criteria, with duration of disease =6 months 3) Those with PCOS of kidney‐yang deficiency and phlegm obstruction type or kidney‐yin deficiency and phlegm‐stasis type in TCM syndrome differentiation; 4) Those who have not received medication or those who have taken medication but stopped it for more than 3 months; 5) Those who have ability to cooperate in observing efficacy and adverse events, as well as recording in the subject diary; 6) Those who voluntarily participate in this clinical study and sign relevant informed consent forms.

ChiCtr (2023). "QuikClear hysteroscopic tissue resection system versus hysteroscopic electroresection in the treatment of submucous fibroids: a single-center prospective randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control group:Hysteroscopic resection.;Experimental group:QuikClear hysteroscopic tissue resection system group; CONDITION: submucous fibroids PRIMARY OUTCOME: Effectiveness; SECONDARY OUTCOME: Security;Postoperative pregnancy;Satisfaction evaluation;Clinical performance; INCLUSION CRITERIA: 1) Patients who voluntarily sign informed consent to participate in the clinical trial on the basis of full understanding after fully explaining the purpose and content of the clinical trial, including the subject's compliance. 2) Age 20‐45 years old 3) Patients with benign uterine lesions were diagnosed after hysteroscopy. 4) Patients with diagnostic curettage or blunt dissociation are difficult to remove. 5) Type 0, type 1 or type 2 uterine submucous fibroids (diameter = 4 cm). 6) Sexual life history.

ChiCtr (2023). "A randomised, double-blind, placebo-control study evaluating the efficacy and safety of hyaluronic acid gel in the treatment of genitourinary syndrome of menopause." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: intervention group:vaginal application of one tube of sodium hyaluronate gel, once every day for the first two weeks and once every 3 days for the following two weeks, with four weeks in total.;placebo control group:vaginal application of one tube of placebo, once every day for the first two weeks and once every 3 days for the following two weeks, with four weeks in total.; CONDITION: genitourinary syndrome of menopause PRIMARY OUTCOME: improvement of symptoms; SECONDARY OUTCOME: improvement of vaginal atrophy symptoms questionnaire, vaginal health inde Xscore, vaginal pH, vaginal maturation inde Xand female sexual function inde Xcompared to baseline;vital signs and physical examination; INCLUSION CRITERIA: 1. aged between 45‐70 (with boundary included) 2. menopause women (with or without hysterectomy) with at least one of following criteria met: a. amenorrhea over 12 months if no hysterectomy was done b. serum FSH level above 40IU/L if currently undergoing amenorrhea between 6‐12 months, or underwent hysterectomy before menopause c. underwent bilateral oophorectomy over 6 months ahead of baseline visit 3. vaginal discharge pH>5.0 4. underwent at least one of the following symptoms and degree of symptoms evaluated as moderate or severe using the VASQ rating scale a. vaginal dryness at least once a week b. vulvovaginal itching at least once a week c. sensation of stimulation at least once a week d. feeling of pain in vulvovaginal area at least once a week e. coital pain at least once a week 5. participants could voluntarily avoid the use of either antibiotics, pre/probiotics, drugs containing estrogen unless permitted. 6. participa

ChiCtr (2023). "A Randomized clinical trial of Postoperative adjuvant therapy with Toripalimab versus cervical lymphadenectomy alone for Residual recurrent nasopharyngeal carcinoma in cervical lymph nodes." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Test group:Cervical lymphadenectomy + Toripalimab;Control group:Cervical lymphadenectomy; CONDITION: Nasopharyngeal carcinoma PRIMARY OUTCOME: failure‐free survival, FFS; SECONDARY OUTCOME: overall survival, OS;distant metastases‐free survival, DMFS;local recurrence‐free survival, LRFS;Safety index;Quality of life; INCLUSION CRITERIA: 1) Age: 18‐70 years. 2) Histologically and/or cytologically confirmed recurrent nasopharyngeal carcinoma non‐keratinizing carcinoma (differentiated or undifferentiated, WHO type II or III; 3) Primary nasopharyngeal and cervical lymph node lesions have been treated with radical dose radiotherapy; 4) Imaging findings of residual or recurrent cervical lymph nodes alone, clinical stage rT0N1‐3M0, no distant metastasis; 5) KPS score = 70; 6) Patients have signed informed consent and are willing and able to comply with the study plan visit, treatment plan, laboratory tests and other study procedures.

ChiCtr (2023). "Randomized controlled study on the effect of acupuncture on ovulation disorders in polycystic ovary syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: A:Acunpuncture;C:Shallow needling of non meridian and non acupoint control points; CONDITION: PCOS PRIMARY OUTCOME: ovulation rate;Menstrual frequency; SECONDARY OUTCOME: Serum se Xhormone levels;Number of cystic follicles;BMI;Waist to Hip Ratio;Medical Outcomes Study,SF‐36; INCLUSION CRITERIA: ? Conforming to PCOS diagnostic standards; ? Age 18‐40 years old; ? Infrequent menstruation (Menstrual cycle>35 days or less than 8 menstruations in the last 12 months) or amenorrhea (menopause time exceeds 90 days); ? The patient voluntarily participates in clinical trials and signs an informed consent form.

ChiCtr (2023). "A randomized controlled trial of the treatment of stress urinary incontinence in women by acupuncture at the ZhongJi point under CT location." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment Group 1:Acupuncture was applied to Zhongji point to the anterior bladder space.;Treatment Group 2:Acupuncture was applied at Zhongji point to 1cm below the abdominal wall.;Control group:Acupuncture was applied to Zhongji point to the fat layer.; CONDITION: SUI PRIMARY OUTCOME: 1h pad test;International Advisory Committee on Incontinence Urinary Incontinence Questionnaire‐short form; INCLUSION CRITERIA: (1) in accordance with the fourth international incontinence recommendations (4 th Edition 2009). ? Symptoms: when the abdominal pressure increases in various degrees, such as sneezing, coughing, laughing, strenuous exercise or walking, urine leakage is involuntary. When the abdominal pressure is stopped, urine flow is stopped. ? Signs: involuntary urine leakage when abdominal pressure increased, or weight gain >1g in pad test; ? No accompanying symptoms such as urgency and frequency of urination. (2) the age is greater than 35 years old and less than 65 years old; (3) signed informed consent and were willing to participate in the study.

ChiCtr (2023). "A randomized controlled, open clinical study comparing the safety and efficacy of transvaginal natural orifice transluminal endoscopic surgery (VNOTES) and single-port transumbilical total laparoscopic hysterectomy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: VNOTES group:Total hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (VNOTES);LESS group:Total hysterectomy by single‐port transumbilical total laparoscopic hysterectomy (LESS); CONDITION: ? Adenomyosis/endometriosis; ? Uterine fibroids; ? cervical intraepithelial lesions; ? Atypical endometrial hyperplasia; ? Other conditions requiring hysterectomy. PRIMARY OUTCOME: Intraoperative and postoperative complications; SECONDARY OUTCOME: Hemoglobin before and after surgery;Pain intensity;Satisfaction; INCLUSION CRITERIA: INCLUSION CRITERIA: =18 years old, < 75 years old, female patients with indications of hysterectomy due to benign diseases according to clinical guidelines, the surgical indications included: ? adenomyopathy/endometriosis; ? Uterine fibroids; ? cervical intraepithelial lesions; ? Atypical endometrial hyperplasia; ? Other conditions requiring hysterectomy.

ChiCtr (2023). "A randomized, double-blind, placebo-controlled, multicenter clinical trial of the efficacy and safety of Ejiao Composite Syrup in the treatment of diminished ovarian reserve (deficiency of qi and blood syndrome)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Treatment Group:Ejiao Composite Syrup;Control Group:Ejiao Composite Syrup Mimetic Agent; CONDITION: Diminished ovarian reserve (deficiency of qi and blood syndrome) PRIMARY OUTCOME: Follicle stimulating hormone; SECONDARY OUTCOME: Pictorial Blood Loss Assessment Chart;Luteinizing Hormone;Prolactin;Progesterone;Estradiol;Testosterone;Anti‐Müllerian Hormone;Antral Follicle Count;Pittsburgh Sleep Quality Index;TCM syndrome curative effect; INCLUSION CRITERIA: 1) Age: 25‐39 years old (including boundary value) female; 2) Meet the diagnostic criteria of diminished ovarian reserve; 3) In accordance with the diagnostic criteria of less menstrual period of TCM; The TCM syndrome differentiation type was "deficiency of qi and blood syndrome". 4) Auxiliary examination: the results of 2 tests within 3 months met the following criteria: 10Miu/mL= Follicle stimulating hormone (FSH) < 25 miU /ml; 5) Menstrual cycle regularity,:21 < menstrual cycle < 35 days,1 day = menstrual period =7 days; 6) No history of intrauterine operation or systemic hormone therapy within 3 months before treatment; 7) Voluntarily sign the informed consent form of the subjects.

ChiCtr (2023). "A randomized, open, positive controlled clinical study to evaluate the efficacy and safety of Baofukang Shuan in the treatment of bacterial vaginosis (BV)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: test group :Baofukangshuan;Control group:Metronidazole vaginal gel; CONDITION: Bacterial vaginosis PRIMARY OUTCOME: Cure rate of BV after 3 to 5 days of discontinuation.; SECONDARY OUTCOME: Cure rate of BV after 28 +/‐ 3 days of discontinuation;Relapse rate of BV after 28 +/‐ 3 days of discontinuation;Improvements in vaginal microecology; INCLUSION CRITERIA: 1. Women aged over 18 years are sexually active; 2. Bacterial vaginosis (BV) was diagnosed; 3. Informed consent and voluntary participation in this study, and signed informed consent.

ChiCtr (2023). "Randomized, open-label, two-treatment, two-cycle, crossover design bioequivalence study of a single oral dose of dienogest tablets in healthy subjects under fed conditions." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Test preparation‐Reference preparation group:cycle 1 the test product was taken orally; cycle 2 reference preparation was taken orally;Reference preparation‐ Test preparation group:cycle 1 reference preparation was taken orally; cycle 2 the test product was taken orally; CONDITION: Endometriosis PRIMARY OUTCOME: Cmax;Tmax;AUC0‐t;AUC0‐8;?z;t1/2;F; INCLUSION CRITERIA: 1)Subjects are fully informed of the purpose of the trial, its content, procedure, and possible adverse effects, volunteered as subjects, and signed an informed consent form prior to the start of any procedure. 2)Healthy female subjects aged 18‐45 years old (inclusive). 3)Subjects should weigh no less than 45 kg. Body mass inde Xwas in the range of 19 to 26 kg/m2 (inclusive). Body mass inde X(BMI) = weight (kg)/height2 (m2). 4)Vital signs, physical examination (skin, mucous membranes, lymph nodes, head, neck, chest, abdomen, bones/muscles, nervous system, etc.), 12‐lead electrocardiogram, gynecologic ultrasound (routine color ultrasound of gynecologic organs), laboratory tests (including routine blood, blood biochemistry, blood pregnancy, coagulation function, routine urine, immune tetralogy) with normal test results or those judged by the clinician to be abnormal without clinical significance. 5)Subjects must have regular menstruation (menstrual cyc

ChiCtr (2023). "Recombinant luteinizing hormone supplementation based on FSH/LH values will improve clinical outcomes with antagonist protocol: a prospective, single-center, single-blind, randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:Administer gene recombinant follicle‐stimulating hormone (r‐FSH) 150‐225u + gene recombinant luteinizing hormone (r‐LH) 75u, inject once a day, for 5 consecutive days, the sixth day of stimulation (the sixth day of stimulation) according to adjust the dosage of r‐LH according to the FSH/LH value (if >= 5r‐LH, increase to 150 u/d, if < 5r‐L1, the dosage remains unchanged) until the night needle day.;Control group:From the start date, r‐FSH (150‐225u) was injected once a day for 5 consecutive days, and 75u r‐LH was added on the 6th day according to the current clinical routine until the night acupuncture day.; CONDITION: Infertility PRIMARY OUTCOME: good‐quality cleavage embryos; SECONDARY OUTCOME: follicle export rate;MII oocyte rate;fertility rate;available embryo rate;good embryo rate;Clinical pregnancy rate;Pregnancy loss rate; INCLUSION CRITERIA: 1. The age of the woman is 20‐40 years old, and the menstrual cycle is normal; 2. Both husband and wife have normal chromosomes; 3. Without adenomyosis and endometriosis; 4. No intramural fibroids > 4 cm, intrauterine adhesions or untreated endometrial polyps.

ChiCtr (2023). "Remimazolam versus propofol sedation on the quality of recovery in patients with painless induced abortion : a randomized non-inferiority trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Remimazolam group:Sufentanil combined with Remazolam for sedation;Propofol group:Sufentanil combined with propofol for sedation; CONDITION: NA PRIMARY OUTCOME: Postoperative quality of recovery‐15; SECONDARY OUTCOME: Incidence of nausea and vomiting after awakening;Injection pain;Time to discharge;Incidence of hypoxemia;Incidence of hypotension;The number and frequency of additional sedative drugs;Recovery time; INCLUSION CRITERIA: (1) Patients undergoing elective, painless induced abortion surgery (2) Age 18‐45 years; (3)BMI18 28kg/m2 (4) Gestation time, 50‐75 days; (5) Blood routine, coagulation routine, urine routine, white ribbon routine, liver and kidney function test results were unremarkable; (6) American Society of anesthesiologists (ASA) class I to II; (7) Informed of the experimental procedure and risks of anaesthesia, volunteered to participate in this study and signed consent for anaesthesia.

ChiCtr (2023). "Research for the Treatment of Female Stress Urinary Incontinence Using Transcutaneous Acupoint Electrical Stimulation Combined with Vaginal Biofeedback Electrical Stimulation." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control group:Biofeedback Electrical Stimulation Therapy via Vaginal Canal;Observation group:TEAS treatment was performed simultaneously with Biofeedback Electrical Stimulation Therapy via Vaginal Canal; CONDITION: N39.300 female stress urinary incontinence PRIMARY OUTCOME: One‐hour pad test;Modified Oxford Muscle Grading Scale;Short Form of International Consultation on Incontinence Questionnaire (ICIQ‐SF); SECONDARY OUTCOME: Pelvic floor muscle electromyography assessment;Short Form of Incontinence Impact Questionnaire (IIQ‐7);Incontinence Quality of Life Scale ( I‐QOL); INCLUSION CRITERIA: Patients with mild to moderate stress urinary incontinence who meet the following criteria: female, aged 20‐40, with clear thinking ability and able to follow verbal or written instructions, who have not received any relevant treatments in the month prior to participation in the study, voluntarily agree to participate in this study, and sign an informed consent form.

ChiCtr (2023). "Safety and efficacy of ultrasound-guided superior hypogastric plexus block combined with conscious sedation in ambulatory patients undergoing percutaneous microwave ablation of uterine myomas: a single-center, double-blinded, randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: the intervention group:ultrasound‐guided superior hypogastric plexus block (SHPB) combined with conscious sedation;the control group:local anesthesia combined with conscious sedation; CONDITION: uterine myomas PRIMARY OUTCOME: the success rate of anesthesia; SECONDARY OUTCOME: vasoactive drug consumption;acetaminophen consumption;sleep quality;the Uterine Fibroid Symptom and Quality of Life Score (UFS‐QOL); INCLUSION CRITERIA: a. Patients with a body mass inde X(BMI) of less than 30.0 kg·m‐2. b. Patients aged 18 to 45 years. c. Patients with American Society of Anesthesiologists (ASA) physical status classes ? and ?. d Ultrasound guided PMWA surgery for uterine fibroids.

ChiCtr (2023). "Sentinel lymph node biopsy in early cervical cancer: a prospective randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: sentinel lymph node biopsy group:sentinel lymph node biopsy;pelvic lymphadenectomy group:pelvic lymphadenectomy; CONDITION: cervical cancer PRIMARY OUTCOME: Recurrence rate; SECONDARY OUTCOME: lymphatic leakage and lymphatic retention cyst;lower limb edema;Intraoperative blood loss and operative time;Postoperative pelvic drainage;Number of pathological lymph node positive cases;Number of cases of postoperative adjuvant chemoradiotherapy;Postoperative quality of life; INCLUSION CRITERIA: (1) Stage IA2‐IB1 was first diagnosed according to the 2018 FIGO clinical staging criteria and no treatment was given; ? Cervical pathological biopsy was diagnosed as cervical squamous cell carcinoma or adenocarcinoma. ? Preoperative MRI and other imaging data showed no lymph node metastasis. (4) Voluntarily participated in the experiment and signed the informed consent

ChiCtr (2023). "A Study of Fluzoparib Maintenance Treatment in Participants With HRD Positive Initially Treated Advanced Ovarian Cancer Following Response on Front-Line Short Cycle Platinum-Based Chemotherapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Cohort 1:After 4 cycles of platinum‐containing chemotherapy, the patient achieved complete clinical remission and began to take fluzopril.;Cohort 2:After 6 cycles of platinum‐containing chemotherapy, the patient achieved complete clinical remission and began to take fluzopril.; CONDITION: Ovarian Cancer PRIMARY OUTCOME: Progression Free Survival Rate at 12 months; SECONDARY OUTCOME: Progression‐free survival;Progression Free Survival Rate at 24 months;Overall survival; INCLUSION CRITERIA: 1.The patients voluntarily participated in this study and signed the informed consentincluding undergoing treatment and scheduled visits and examinations 2.Patients must be female 18‐75 years of age 3.Newly diagnosed ovarian cancer, fallopian‐tube cancer, or primary peritoneal cancer, that is stage III or IV according to International Federation of Gynecology and Obstetrics [FIGO] 4.Patients with histologically confirmed, high grade serous or high grade endometrioid ovarian cancer, fallopian‐tube cancer or primary peritoneal cancer. 5.Satisfactory primary debulking surgeryno visible residual tumor or residual tumor=1cm(R0/R1) 6.After surgery, complete response ( CR ) was achieved after platinum‐based chemotherapy, and screening should be completed within 8 weeks after the last dose of chemotherapy ; according to the RECIST1.1 standard, the disease was completely relieved ( CR ), and CA‐125 was within the upper limit of normal ( ULN ) or not incre

ChiCtr (2023). "Study on psychological status of young patients with induced abortion by multimodal health education." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:Multi mode health education;control group:reguar post abortion care; CONDITION: induced abortion PRIMARY OUTCOME: Anxiety Scale;Depression Scale; INCLUSION CRITERIA: 1. Patients aged 14‐19 years; 2. The gestational age is within 12 weeks; 3. The patient and guardian voluntarily participated in the study and signed the informed consent form.

ChiCtr (2023). "A study on the application of a mental health promotion program for women with polycystic ovary syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group :Mindfulness integrated cognitive‐behavioral therapy + lifestyle ;Intervention group:lifestyle ;control group :waiting in the list; CONDITION: Polycystic ovary syndrome PRIMARY OUTCOME: depression;anxiety; SECONDARY OUTCOME: body image distress;subjective well‐being;Body Mass Inde X(BMI); INCLUSION CRITERIA: (1) Meet the diagnostic criteria in "Diagnosis of Polycystic Ovary Syndrome: Health Industry Standards of the People's Republic of China" approved in 2011; (2) Age = 18 years old; (3) PHQ‐9 = 5 or GAD‐7 = 5 or both PHQ‐9 and GAD‐7 = 5; (4) Voluntarily participate in this study

ChiCtr (2023). "Study on the Effect of Huolong Cupping Comprehensive Moxibustion Therapy on Preventing VTE Formation in Patients Undergoing Gynecological Laparoscopic Surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group:Routine perioperative care;Test group:Intervention was conducted on the day before surgery and the first, third, and fifth days after surgery, with a total of 4 treatments. Hand contact with the skin first and then drop the jar, using a combination of pushing, scraping, and moxibustion for operation. Moxibustion and scraping were performed in the order of Taixi, Sanyinjiao, Fenglong, Zusanli, Chengshan, Yanglingquan, Weizhong, Xuehai, Futu, and Yinmen, while moxibustion was performed on Yongquan acupoint with Ai box. Hold the jar with one hand, first test the temperature, then lower the jar. After lowering the jar, use wrist force to rotate the warm moxibustion and push the jar on the corresponding acupoints with the patient s tolerable strength, to avoid the appearance of fever. Moxibustion and scraping at each acupoint will take about 1 minute, and the entire operation will take about 20 minutes.; CONDITION: venous thromboembolism PRIMARY OUTCOME: Incidence of VTE;Fibrinolysis 2 items; SECONDARY OUTCOME: Caprini Thrombosis Risk Factor Assessment Form;Comfort Rating Scale;coagulation; INCLUSION CRITERIA: (1) Patients undergoing laparoscopic surgery for benign and malignant gynecological tumors; (2) Those with complete clinical data; (3) Between the ages of 18 and 60; (4) Informed consent and voluntary participation in this study; (5) Able to withstand ultrasound examination; (6) Conscious, without mental illness or cognitive impairment, able to communicate effectively, and able to complete the assessment scale;

ChiCtr (2023). "Study on the effect of TCM TEAS on the prevention and treatment of PONV after gynecological laparoscopic surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: TEAS group:30min before anesthesia, the percutaneous acupuncture points were continuously given to the acupuncture points of Jinghegu, Neiguan, Zusanli and Sanyin until the end of the operation.;Control group:The patient was given a sham acupuncture 30min before anesthesia (1cm to take the acupoint next to Hegu, Neiguan, Zusanli and Sanyinjiao, connected to the stimulator, and no electrical stimulation) until the end of the operation.; CONDITION: Nausea and vomiting after general anesthesia PRIMARY OUTCOME: Postoperative nausea and vomiting; SECONDARY OUTCOME: C‐reactive protein;Interleukin‐6;Interleukin ‐10 ;Tumor necrosis factor‐a;creatine kinase; INCLUSION CRITERIA: Patients undergoing elective gynecological laparoscopic surgery under general anesthesia (1) Patients hospitalized for laparoscopic gynecological surgery; (2) Preoperative general condition can be, ASA grade I III; Age 18‐65 years old (3) patients can communicate normally, there are no obvious contraindications to acupuncture; (4) The skin of the limbs is intact, suitable for acupuncture; (5) The patient and family sign the informed consent form.

ChiCtr (2023). "Study on the efficacy and safety of esketamine combined with remazolam in anesthesia for daytime abortion surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: group RM1:Anesthesia was induced with esketamine combined with remimazolam 0.2mg/kg, and to determine the half effective dose of esketamine combined with different doses of remazolam to inhibit the body response of patients undergoing daytime painless abortion during cervical dilation .;group RM2:Anesthesia was induced with esketamine combined with remimazolam 0.3mg/kg, and to determine the half effective dose of esketamine combined with different doses of remazolam to inhibit the body response of patients undergoing daytime painless abortion during cervical dilation ;group RM3:Anesthesia was induced with esketamine combined with remimazolam 0.4mg/kg, and to determine the half effective dose of esketamine combined with different doses of remazolam to inhibit the body response of patients undergoing daytime painless abortion during cervical dilation .; CONDITION: daytime painless abortion surgery PRIMARY OUTCOME: median effective dose;body movement response;adverse events;non‐invasive blood pressure;heart rate;SPO2;sedation;drug use;vital signs; SECONDARY OUTCOME: Narcotrend index;visual analogue scale;BPS score;time of anesthesia induction;time of operation;time of awakening;time of leaveing the operating room;Modified MOAA/S score;Modified alderete score; INCLUSION CRITERIA: (1) Age: 18‐50 years old (2) BMI:18kg/?‐30kg/? (3) ASA : I‐II (4) Patients with 4‐10 weeks of pregnancy and surgical indications for outpatient day‐time painless abortion (5) The patient has informed consent to the surgical protocol and experimental protocol

ChiCtr (2023). "Study on the Improvement of Polycystic Ovarian Syndrome patients with overweight / obesity by standardizing medical nutrition management and probiotic treatment." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: A(PCOS):None;B:Standardized nutrition management and placebo;C:Standardized nutrition management and probiotic;D(healthy control):None; CONDITION: Polycystic Ovarian Syndrome PRIMARY OUTCOME: Fasting blood glucose ;Insulin;Total cholesterol;Triglyceride;High‐density lipoprotein cholesterol;Low‐Density Lipoprotein Cholesterol;body weight;waist;Body fat percentage;Body Mass Index; SECONDARY OUTCOME: gut microbiota; INCLUSION CRITERIA: Control group: (1) age:18 40, 18.5=BMI<23.9kg/m^2 (2) No history of gastrointestinal diseases such as diarrhea within 4 weeks, and no anomaly in stool exam. (3) No history of allergic diseases such as asthma and allergic cough. (4) No treatment of probiotic, prebiotic, postbiotic or antibiotic within 2 weeks PCOS group: (1)2003 Rotterdam Standard Diagnosis of PCOS (2)BMI =24 kg/m^2 (3) age:18 40

ChiCtr (2023). "Study on therapeutic effect of acupuncture myofascial trigger point combined with abdominal stretch on primary dysmenorrhea in athletes." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: MTrPs alone acupuncture group:MTrPs alone acupuncture ;MTRPS combined with abdominal stretch therapy group:MTRPS combined with abdominal stretch therapy;Traditional microwave TDP combined with stretching therapy group:Traditional microwave TDP combined with stretching therapy; CONDITION: Primary dysmenorrhea PRIMARY OUTCOME: Pain condition;Functional assessment;Physical indicators;Sports Performance; INCLUSION CRITERIA: (1) met the diagnostic criteria for primary dysmenorrhea; (2) female athletes aged 18‐35 years; (3) premenstrual pain intensity =4 points (0‐10 VAS scores) ; (4) had premenstrual pain symptoms for at least 6 months; (5) not pregnant or not planning to become pregnant during the study period; (6) no serious heart, liver, kidney, nervous system, endocrine system diseases; (7) has not used analgesics or other drugs or methods for the treatment of PDM in the past 4 weeks; (8) is willing to follow the study protocol and sign an informed consent form.

ChiCtr (2023). "The Therapeutic Effect of Transcutaneous Electrical Acupoint Stimulation on Primary Dysmenorrhea." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention group:Transcutaneous electrical acupoint stimulation;Control group:Sham‐Transcutaneous electrical acupoint stimulation; CONDITION: Primary dysmenorrhea PRIMARY OUTCOME: Pain;Total effect rate;Uterine artery hemodynamics; SECONDARY OUTCOME: Mental health;Quality of life; INCLUSION CRITERIA: 1) Ultrasound examination shows no organic lesions in the reproductive organs; 2) Age 18‐40 years old; 3) Menstrual cycle regularity: 28 ± 7 days; 4) VAS score = 4 cm (moderate or above pain) at the baseline; 5) Willing to complete the corresponding questionnaire check and sign the informed consent form.

ChiCtr (2023). "To investigate the effect of ultrasound-guided TAP block on neutrophil/platelet to lymphocyte ratio in patients undergoing radical resection of endometrial cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: TAPB+GA group:Transversus abdominis plane block combined with general anesthesia;GA group:general anesthesia; CONDITION: Endometrial Cancer PRIMARY OUTCOME: Neutrophil to lymphocyte ratio; SECONDARY OUTCOME: Platelet to lymphocyte ratio;VAS score;Nausea and vomiting; INCLUSION CRITERIA: ? Age 20‐70 years old; ? All patients were diagnosed as endometrial cancer for the first time without any systemic treatment, and confirmed as endometrial cancer by postoperative pathology; ?ASA grade I‐III; ? No distant metastasis of other sites occurred; ? The operation was performed by the same group of surgeons.

ChiCtr (2023). "To investigate whether probiotics can delay the development of paraneoplastic thrombocythemia in patients with ovarian cancer through their effects on intestinal flora." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group1:Bifidobacterium longum;Group2:Placebo; CONDITION: Ovarian Cancer PRIMARY OUTCOME: platelets;Fecal flora; SECONDARY OUTCOME: CA125;HE4;Coagulation function; INCLUSION CRITERIA: 1. Ovarian cancer patients with PLT count greater than 300 X10^9/L; 2. Epithelial ovarian cancer (serous adenocarcinoma, mucous adenocarcinoma, endometrioid adenocarcinoma, etc.) was confirmed by puncture pathology or highly suspected ovarian cancer was confirmed by postoperative pathology; 3. The patient was generally in good condition, aged 18‐75 years, and did not have serious heart, lung, kidney, liver dysfunction or metabolic diseases.; 4. 6 courses of TC chemotherapy were received after surgery; Fresh, meso‐posterior, and internal fecal samples of 10 g were collected and quickly stored at ‐80 degree C. Fecal DNA extraction and 16S rRNA gene sequencing were performed for intestinal flora detection; 5. No antibiotics or other drugs were used in the first 3 months after the completion of treatment.

ChiCtr (2023). "Ultrasound-Guided erector spinae plane block for postoperative analgesia in patients undergoing posterior cervical spine surgery: a randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Experimental group:erector spinae plane block;Control group:local infiltration analgesia; CONDITION: Cervical spondylosis combined with spinal stenosis, spinal tumors, and cervical instability PRIMARY OUTCOME: Dosage of morphine within 24 h after surgery; SECONDARY OUTCOME: Intraoperative consumption of opioids;Postoperative Visual Analogue Scale Score;Times of sleep interruption due to pain on the night of surgery;Time until the first walkout of bed after surgery;Time to hospital discharge; The total cost of hospitalization;Total morphine consumption during hospitalization;postoperative adverse events; INCLUSION CRITERIA: (1) PCSS are indicated for patients with cervical spondylosis with posterior longitudinal ligament calcification, cervical spondylosis with spinal canal stenosis, cervical spondylosis with arachnoiditis, spinal canal tumor, and cervical instability; (2) Ages of 18‐60 years with gender restriction; (3) The preoperative American Society of anesthesiologists (ASA) anesthesia risk assessment grade is I to II; (4) Patients who signed informed consent.

ChiCtr (2024). "Impact of three endothelial preparation protocols on clinical outcomes of first transfer of frozen-thawed embryos in patients with PCOS: a prospective randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: HRT:Endothelial preparation using a hormone replacement program;GnRH‐a HRT:Endothelial preparation using a GnRH‐a hormone replacement program;LE:Endothelial preparation with letrozole; CONDITION: PCOS PRIMARY OUTCOME: Clinical pregnancy rate; SECONDARY OUTCOME: pregnancy outcome;neonatal outcome;Safety indicators; INCLUSION CRITERIA: (1) <38 years of age; (2) Diagnosis of PCOS after exclusion of other endocrine disorders and fulfillment of 2 of the Rotterdam criteria: polycystic changes of the ovaries (PCOM); clinical manifestations of hyperandrogenism and/or hyperandrogenemia; and menstrual abnormalities such as sporadic ovulation or anovulation; (3) Patients with indications for IVF/ICSI‐FET procedure; (4) Hysteroscopy within 12 months did not show significant abnormalities; (5) Patients and their families voluntarily participated in this study, understood the related rights and risks, and signed an informed consent form.

ChiCtr (2024). "A multicenter, randomized, double-blind, placebo-controlled study to evaluate the effect of Zishen Yutai Pill on IVF outcomes in young women with expected ovarian hyporesponsiveness (Poseidon Group 3) and explore the mechanism of follicular fluid metabolism." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: intervention:Zishen Yutai Pill treatment+GnRH antagonist protocol;control:GnRH antagonist protocol; CONDITION: infertility PRIMARY OUTCOME: number of oocytes retrieved; SECONDARY OUTCOME: Duration of use of exogenous gonadotropins;total exogenous gonadotropin dose;average daily dose of exogenous gonadotropins;Serum E2 (pg/ml) and P (ng/ml) levels on the trigger day;fertilization number;Number of transferable embryos;Number of top quality embryos (TQE);Mature oocyte rate (M ? oocyte rate);Cycle cancellation rate;positive pregnancy test;implantation rate;clinical pregnancy;Early spontaneous abortion ;threatened abortion;ectopic pregnancy;Multiple pregnancy ;Persistent pregnancy; INCLUSION CRITERIA: (1) Women aged = 20 years old,<35 years old, married and diagnosed as infertile; (2) Planned IVF/ICSI treatment; (3) Low ovarian reserve (anti Mullerian hormone (AMH) levels<1.2 ng/ml and/or antral follicle count (AFC)<5).

ChiCtr (2024). "RCT study on pregnancy outcomes of different timing of thawing and transfer in frozen-thawed single blastocyst transfer cycles." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control group :LH surge + 7 days thawing transplantation group ;test group:Thawed transplantation 12 hours earlier.; CONDITION: Infertility PRIMARY OUTCOME: Blastocyst implantation rate per transfer cycle; SECONDARY OUTCOME: Ectopic pregnancy rate;HCG positive rate;Clinical pregnancy rate; INCLUSION CRITERIA: (1) Age < 40 years; (2) frozen‐thawed embryo transfer cycles; (3) endometrial preparation protocol for natural cycles or microstimulation cycles; (4) D5/D6 high‐quality single blastocyst transfer cycles without C.

Chidambaram, V., et al. (2022). "A randomised comparative study of sublingual and vaginal misoprostol for cervical priming before minor gynaecological procedures." Journal of Obstetrics and Gynaecology 42(6): 2297-2301.
	This study aimed to compare the effect of misoprostol using vaginal or sublingual routes on the non-pregnant uterine cervix prior to minor gynaecological procedures. One hundred and forty women were randomised 1:1 into two groups: A and B. Group A received misoprostol 400 mcg vaginally and pyridoxine 40 mg sublingually and Group B received misoprostol 400 mcg sublingually and pyridoxine 40 mg vaginally 4 h prior to procedure. The outcomes studied were maximum size of Hegar's dilator that could be inserted into the cervix without any resistance, ease of dilatation, need and time required for further dilatation, side effects and complications. Baseline cervical dilatation was significantly more in Group A than Group B. Need for further dilatation and time required for further dilatation were also significantly less in Group A than Group B. Thus, we conclude that vaginal misoprostol is more effective than sublingual misoprostol in cervical priming before minor gynaecological procedures. Clinical Trial Registration Number:www.ctri.nic.in; CTRI/2018/07/015080 IMPACT STATEMENTWhat is already known on this subject? Cervical priming has been shown to result in shorter operative time, easier mechanical dilatation, reduced incidence of complications and blood loss when used prior to surgical abortion and has been recommended as a standard practice in various national and international guidelines for safe abortion practices. Misoprostol has many advantages over other ripening agents like osmotic dilators, other prostaglandins and mifepristone. Misoprostol can be given through oral, sublingual, vaginal, buccal and rectal routes. Use of misoprostol has been found to improve cervical dilatation, reduce need of further dilatation and ease of dilatation without many complications when compared to placebo for cervical priming of non-pregnant cervix. Studies comparing vaginal and sublingual routes have shown no significant difference for cervical ripening in pregnant women. What the results of this study add? We found that vaginal misoprostol for cervical priming was more effective than sublingual misoprostol in reaching a higher baseline cervical dilatation, with reduced need and time required for further dilatation before minor gynaecological procedures, although the ease of dilatation was similar in both groups. This effect of vaginal misoprostol was more marked in premenopausal women. What the implications are of these findings for clinical practice and/or further research? The results of our study are at variance with other studies done on use of misoprostol via the vaginal or sublingual routes, and hence it is imperative that large multi-center studies be performed to bring about consensus on the topic.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Chien, T. J., et al. (2024). "Head-to-Head Comparison of Electroacupuncture and Laser Acupuncture Effects on Autonomic Regulation and Clinical Effects in Dysmenorrhea: A Randomized Crossover Clinical Trial." Journal of Integrative and Complementary Medicine.
	Introduction: Electroacupuncture (EA) has been applied in dysmenorrhea and has shown good efficacy. The mechanisms of EA are associated with autonomic nervous system adjustments and neuroendocrine regulation. Laser acupuncture (LA), however, has been widely investigated for its noninvasiveness. However, it remains uncertain whether LA is as effective as EA. This study aimed to compare EA and LA head to head in dysmenorrhea. Method(s): A crossover, randomized clinical trial was conducted. EA or LA was applied to selected acupuncture points. Participants were randomized into two sequence treatment groups who received either EA or LA twice per week in luteal phase for 3 months followed by 2-month washout, then shifted to other groups (sequence 1: EA > LA; sequence 2: LA > EA). Outcome measures were heart rate variability (HRV), prostaglandins (PGs), pain, and quality-of-life (QoL) assessment (QoL-SF12). We also compared the effect of EA and LA in low and high LF/HF (low frequency/high frequency) status. Result(s): Totally, 43 participants completed all treatments. Both EA and LA significantly improved HRV activity and were effective in reducing pain (Visual Analog Scale [VAS]; EA: p < 0.001 and LA: p = 0.010) and improving QoL (SF12: EA: p < 0.001, LA, p = 0.017); although without intergroup difference. EA reduced PGs significantly (p < 0.001; d p = 0.068). In low LF/HF, EA had stronger effects than LA in increasing parasympathetic tone in respect of percentage of successive RR intervals that differ by more than 50 ms (pNN50; p = 0.053) and very low-frequency band (VLF; p = 0.035). Conclusion(s): There is no significant difference between EA and LA in improving autonomic nervous system dysfunction, pain, and QoL in dysmenorrhea. EA is prominent in PGs changing and preserving vagus tone in low LF/HF; yet LA is noninvasive for those who have needle phobia. Whether LA is equivalent with EA and the mechanism warrants further study. Clinical trial identification number: NCT04178226.Copyright © Mary Ann Liebert, Inc.

Chien, Y., et al. (2021). "Effects of curcuminoids in the treatment of polycystic ovary syndrome: a meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Chien, Y.-J., et al. (2021). "Effects of Curcumin on Glycemic Control and Lipid Profile in Polycystic Ovary Syndrome: Systematic Review with Meta-Analysis and Trial Sequential Analysis." Nutrients 13(2).
	The therapeutic effects of curcumin for polycystic ovary syndrome (PCOS) remain inconclusive. The present study aims to evaluate the effects of curcumin on glycemic control and lipid profile in patients with PCOS. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from the inception through 28 November 2020. Randomized control trials (RCTs), which enrolled adult patients with PCOS, compared curcumin with placebo regarding the glycemic control and lipid profile, and reported sufficient information for performing meta-analysis, were included. Three RCTs were included. Curcumin significantly improves fasting glucose (mean difference (MD): -2.77, 95% confidence interval (CI): -4.16 to -1.38), fasting insulin (MD: -1.33, 95% CI: -2.18 to -0.49), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (MD: -0.32, 95% CI: -0.52 to -0.12), and quantitative insulin sensitivity check index (QUICKI) (MD: 0.010, 95% CI: 0.003-0.018). It also significantly improves high-density lipoprotein (MD: 1.92, 95% CI: 0.33-3.51) and total cholesterol (MD: -12.45, 95% CI: -22.05 to -2.85). In contrast, there is no statistically significant difference in the improvement in low-density lipoprotein (MD: -6.02, 95% CI: -26.66 to 14.62) and triglyceride (MD: 8.22, 95% CI: -26.10 to 42.53) between curcumin and placebo. The results of the fasting glucose, fasting insulin, HOMA-IR, QUICKI, and total cholesterol are conclusive as indicated by the trial sequential analysis. Curcumin may improve glycemic control and lipid metabolism in patients with PCOS and metabolic abnormality without significant adverse effects. Further studies are advocated to investigate the potential effects of curcumin on hyperandrogenism.

Chiengthong, K., et al. (2022). "Effect of vaginal estrogen in postmenopausal women using vaginal pessary for pelvic organ prolapse treatment: a randomized controlled trial." International Urogynecology Journal 33(7): 1833-1838.
	Introduction and Hypothesis: Evidence and recommendations for the use of intravaginal estrogen for prevention of bacterial vaginosis and pessary-related complications are limited and controversial. We hypothesized that adding intravaginal estrogen to pessary use would decrease the incidence of bacterial vaginosis and other pessary-related complications.; Methods: A single-center, open-label, randomized, parallel study was conducted between April 2018 and August 2020. Participants were randomized to either receive intravaginal estriol 0.03 mg plus Lactobacillus acidophilus 100 million viable cell vaginal tablets or have no treatment. The Amsel criteria, normal flora index, visual analog scale, Thai version of the ICIQ-VS (International Consultation on Incontinence Questionnaire-Vaginal symptoms) questionnaire, vaginal abrasions and vaginal bleeding were evaluated at entry and at 2- and 14-week follow-up.; Results: Seventy-eight women were included and randomized to two groups (39 women per group). At 2-week follow-up, one participant in the intervention group and two participants in the control group were diagnosed with bacterial vaginosis (2.7% vs. 5.7%, p = 0.609). At 14-week follow-up, two participants in the intervention group and two participants in the control group were diagnosed with bacterial vaginosis (5.7% vs. 6.2%, p = 0.926). Normal flora index was significantly different at 2-week follow-up [8 (6.3) vs. 5 (6.0), p = 0.032]. There was no significant difference in the visual analog scale, Thai version of the ICIQ-VS, vaginal abrasions and vaginal bleeding between the 2- and 14-week follow-ups.; Conclusions: This study shows no benefit of intravaginal estrogen in reducing bacterial vaginosis, vaginal abrasions, vaginal bleeding and pain in postmenopausal women using a vaginal pessary for pelvic organ prolapse treatment. (© 2021. The International Urogynecological Association.)

Chihara, D., et al. (2022). "Early drug development in solid tumours: analysis of National Cancer Institute-sponsored phase 1 trials." Lancet (London, England) 400(10351): 512-521.
	Background: The low expectation of clinical benefit from phase 1 cancer therapeutics trials might negatively affect patient and physician participation, study reimbursement, and slow the progress of oncology research. Advances in cancer drug development, meanwhile, might have favourably improved treatment responses; however, little comprehensive data exist describing the response and toxicity associated with phase 1 trials across solid tumours. The aim of the study is to evaluate the trend of toxicity and response in phase 1 trials for solid tumours over time.; Methods: We analysed patient-level data from the Cancer Therapy Evaluation Program of the National Cancer Institute-sponsored investigator-initiated phase 1 trials for solid tumours, from Jan 1, 2000, to May 31, 2019. We assessed risks of treatment-related death (grade 5 toxicity ratings possibly, probably, or definitely attributable to treatment), all on-treatment deaths (deaths during protocol treatment regardless of attribution), grade 3-4 toxicity, and proportion of overall response (complete response and partial response) and complete response rate in the study periods of 2000-05, 2006-12, and 2013-2019, and evaluated their trends over time. We also analysed cancer type-specific and investigational agent-specific response, and analysed the trend of response in each cancer type over time. Univariate associations of overall response rates with patients' baseline characteristics (age, sex, performance status, BMI, albumin concentration, and haemoglobin concentration), enrolment period, investigational agents, and trial design were assessed using risk ratio based on the modified Poisson regression model.; Findings: We analysed 465 protocols that enrolled 13 847 patients using 261 agents. 144 (31%) trials used a monotherapy and 321 (69%) used combination therapies. The overall treatment-related death rate was 0·7% (95% CI 0·5-0·8) across all periods. Risks of treatment-related deaths did not change over time (p=0·52). All on-treatment death risk during the study period was 8·0% (95% CI 7·6-8·5). The most common grade 3-4 adverse events were haematological; grade 3-4 neutropenia occurred in 2336 (16·9%) of 13 847 patients, lymphopenia in 1230 (8·9%), anaemia in 894 (6·5%), and thrombocytopenia in 979 (7·1%). The overall response rate for all trials during the study period was 12·2% (95% CI 11·5-12·8; 1133 of 9325 patients) and complete response rate was 2·7% (2·4-3·0; 249 of 9325). Overall response increased from 9·6% (95% CI 8·7-10·6) in 2000-05 to 18·0% (15·7-20·5) in 2013-19, and complete response rates from 2·5% (2·0-3·0) to 4·3% (3·2-5·7). Overall response rates for combination therapy were substantially higher than for monotherapy (15·8% [15·0-16·8] vs 3·5% [2·8-4·2]). The overall response by class of agents differed across diseases. Anti-angiogenesis agents were associated with higher overall response rate for bladder, colon, kidney and ovarian cancer. DNA repair inhibitors were associated with higher overall response rate in ovarian and pancreatic cancer. The rates of overall response over time differed markedly by disease; there were notable improvements in bladder, breast, and kidney cancer and melanoma, but no change in the low response of pancreatic and colon cancer.; Interpretation: During the past 20 years, the response rate in phase 1 trials nearly doubled without an increase in the treatment-related death rate. However, there is significant heterogeneity in overall response by various factors such as cancer type, investigational agent, and trial design. Therefore, informed decision making is crucial for patients before participating in phase 1 trials. This study provides updated encouraging outcomes of modern phase 1 trials in solid tumours.; Funding: National Cancer Institute.; Competing Interests: Declaration of interests RL has served as a consultant for Monte Rosa Therapeutics. CRF has served as a consultant for AbbVie, AstraZeneca, Bayer, BeiGene, Bristol Meyers Sqibb/Celgene, Denovo Biopharma, Genen ech/Roche Pharma, Genmab, Gilead Sciences, Karyopharm Therapeutics, Morphosys, Pharmacyclics/Janssen, Seagen, and Spectrum Pharmaceuticals; and has received research funding paid to the institution from 4D, AbbVie, Acerta Pharma, Adaptimmune, Allogene Therapeutics, Amgen, Bayer, Celgene, Cellectis, EMD, Gilead Sciences, Genentech/Roche, Guardant, Iovance Biotherapeutics, Janssen, Kite Pharma, MorphoSys, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TG Therapeutics, Xencor, Ziopharm, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, V Foundation for Cancer Research, and the Cancer Prevention and Research Institute of Texas where he is a CPRIT Scholar in Cancer Research. LJN has received research support from BMS/Celgene, Caribou Biosciences, Epizyme, Genentech, Gilead/Kite, IGM Biosciences, Janssen, Novartis, Takeda, and TG Therapeutics; and has served as consultant for ADC Therapeutics, Bayer, BMS/Celgene, Epizyme, Genentech, Gilead/Kite, Janssen, Morphosys, Novartis, Takeda, and TG Therapeutics. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Child, T. J., et al. (2021). "A RANDOMISED CONTROLLED BLINDED TRIAL ASSESSING THE EFFECTIVENESS OF EMBRYOGLUE AS AN EMBRYO TRANSFER MEDIUM IN IVF CYCLES." Fertility and Sterility 116(3): e4.
	Objective: To assess if the use of a hyaluronin‐enriched embryo transfer medium [EmbryoGlue (Vitrolife, Sweden)] results in higher live birth rates in IVF cycles compared to standard transfer medium. Materials and Methods: A single centre randomised controlled blinded study recruiting patients between 2017 and 2019. The study included women aged 18 ‐ 45 years having fresh or frozen transfer of 1‐2 cleavage stage embryos or blastocysts. Sample size: Based on the unit’s average live birth rate per embryo transfer in all patients of 32%, to show an increase in the live birth rate to 42% with power of 80% and significance at 5%, 730 patients were required. 10% live birth increase based on published RCT data. Fresh IVF patients had a long agonist or short antagonist protocol. Ovarian stimulation achieved with Gonal‐F or Menopur. IVF or ICSI used as required and embryos cultured individually in Sydney IVF sequential media (COOK Medical, Sydney) overlaid with SAGE Oil (Origio, Denmark). For frozen transfers endometrial preparation was achieved with a natural or medicated (estrogen and GnRH antagonist plus vaginal progesterone) regime. Up to two cleavage stage embryos or blastocysts transferred trans‐cervically using a Wallace Sureview catheter under abdominal ultrasound scan guidance. After consent, patients were randomised using sealed, numbered opaque envelopes. The patient, and the clinician performing the ET were blinded as to study group. Unblinding could occur when the cycle outcome was known (live birth or failed cycle). For statistical analysis, the Chi‐square, Fisher's exact, and Student T tests were used as appropriate. For patients randomised to EmbryoGlue the manufacturer’s instructions were followed with embryos placed in warmed and pre‐equilibrated EmbryoGlue for 10 to 30 minutes before transfer. For patients randomised to the control group embryos were placed in warmed, pre‐equilibrated COOK culture media. Dishes were not overlayed with oil. Results: 731 women were randomised to Group A (standard media) or Group B (EmbryoGlue). There were no differences in patient characteristics between the two groups. Following randomisation, 50 patients did not have ET mostly due to development of OHSS symptoms requiring freeze‐all in a fresh cycle. On an ITT basis the live birth rate per cycle was 37.5% (137/365) vs 35.7% (131/366) (p=NS) and on a per‐protocol (ie actually having ET) 40.5% (137/338) vs 38.2% (131/343) (p=NS) in Groups A and B respectively. There was no statistical difference in live birth rate between the standard or EmbryoGlue culture groups when comparing fresh vs frozen, and cleavage or blastocyst stage transfers. There was no difference in implantation, miscarriage, ectopic or multiple pregnancy rates between the study groups. Conclusions: There is no improvement in live birth rate with the use of a hyaluronin‐enriched embryo transfer medium such as EmbryoGlue during IVF treatment cycles. Impact Statement: In a randomised, controlled, blinded and suitably powered study performed in an academic IVF unit the use of a hyaluronin‐enriched embryo transfer medium (EmbryGlue) did not improve IVF outcome.

Chilimoniuk, Z., et al. (2022). "Molecular methods for increasing the effectiveness of ovarian cancer treatment: a systematic review." Future oncology (London, England) 18(13): 1627-1650.
	Background: The aim of the current study is to analyze and summarize the latest research on improving therapy in ovarian cancer. Materials & methods: Data analysis was based on a review of publications from 2011 to 2021 in the PubMed database with use of the search terms including 'EGFR ovarian cancer', 'folate receptor inhibitors ovarian cancer', 'VEGF ovarian cancer', 'PDGF ovarian cancer' and 'CTLA-4 ovarian cancer'. Results: 6643 articles were found; 238 clinical trials and randomized control trials were analyzed; 122 studies were rejected due to inconsistency with the topic of the work. Conclusion: Extensive research on the treatment of ovarian cancer increases the chance of developing the most effective therapy suited to the individual needs of the patient.

Chin, C. and S. Damast (2022). "Radiation therapy in the definitive management of medically inoperable endometrial cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(3): 323-331.
	The incidence of endometrial cancer continues to increase worldwide with growing life expectancy and rates of obesity. While endometrial cancer is primarily a surgical disease managed with hysterectomy, a small proportion of patients are deemed to be poor surgical candidates due to their co-morbidities. These medically inoperable patients should be considered for curative treatment with definitive radiation therapy, and brachytherapy is an integral component of their care. Referral to a high-volume center early on in the care of potentially inoperable patients is crucial to optimize their management. These patients should be evaluated by a high-risk surgical and anesthesia team to confirm their medical inoperability. For inoperable patients, use of image-guided brachytherapy is encouraged. Brachytherapy applicator selection is determined based on a patient's anatomy, uterine size, and extent of tumor. Advances in anatomic and functional imaging including multiparametric magnetic resonance imaging (MRI) have improved clinical staging of these patients and have also allowed for the delivery of three-dimensional image-guided brachytherapy with improved accuracy. With recent consensus guidelines to guide local computed tomography and/or MRI volume-based delineation of targets and organs-at-risk, local outcomes have improved and treatments are delivered with less acute and late morbidity. Ongoing trials are looking at novel systemic agents, such as immunotherapy, to induce a systemic anti-tumor immune response and improve outcomes in these patients.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Ching, H., et al. (2023). "The effectiveness of technology-based cognitive behavioral therapy on perinatal depression and anxiety: A systematic review and meta-analysis." Worldviews on Evidence-based Nursing 20(5): 451-464.
	BACKGROUND: Extensive literature has shown the effectiveness of cognitive behavioral therapy in treating perinatal depression, but little is known about the effectiveness of its technology-based version. AIM: The aim of this review was to examine the effectiveness of technology-based cognitive behavioral therapy in reducing depressive and anxiety symptoms in women suffering from or at risk of experiencing perinatal depression. METHOD(S): Six electronic databases were searched until February 2023 for articles published in English. Random-effect meta-analyses were conducted. Heterogeneity was assessed using the I2 statistics and Cochran's Q chi-squared test. Sensitivity analyses and subgroup analyses were also performed, and quality appraisals at the study and outcome levels were conducted. RESULT(S): A total of 16 randomized controlled trials were included in the review. Results from meta-analyses suggest that technology-based cognitive behavioral therapy has a medium effect in reducing perinatal depressive symptoms and a small effect in reducing perinatal anxiety symptoms. Overall, women suffering from or at risk of perinatal depression may benefit from technology-based cognitive behavioral therapy. LINKING EVIDENCE TO ACTION: Future interventions can be improved by addressing both perinatal depression and anxiety, paying more attention to antenatal women to prevent postnatal mental health issues, and using self-guided mobile applications for accessibility.Copyright © 2023 Sigma Theta Tau International.

Chinthakanan, O., et al. (2022). "Rate of postoperative urinary retention after anterior compartment prolapse surgery, comparing early versus conventional transurethral catheter removal: a randomized controlled trial." International Urogynecology Journal 33(Supplement 1): S61-S62.
	Introduction: Indwelling transurethral catheter is required to prevent postoperative urinary retention after prolapse surgery. To minimize risk of urinary retention and patient's discomfort, the catheter should be removed as soon as possible. Objective(s): The objective was to compare the rate of postoperative urinary retention (POUR) after anterior prolapse surgery in an early transurethral catheter removal (24 hours post-operative) and our standard practice of postoperative day 3. Method(s): A randomized controlled study was conducted, patients undergoing anterior compartment prolapse surgery between March of 2020 and February of 2021 in a university hospital. Women were randomized into two groups. In an early and conventional group transurethral catheter was removed on 24 hours post-operative and 3 postoperative days, respectively. After removal, if the second void residual urine volume exceeded 150 ml, POUR was diagnosed and intermittent catheterization was performed (Figure 1 and 2). The primary outcome was the rate of POUR. The secondary outcomes included urinary tract infection (UTI), asymptomatic bacteriuria (AB), time to ambulation, time to spontaneous void, length of hospitalization and patient satisfaction using Patient Global Impression Scale of Improvement (PGI-I). Result(s): A total of 68 women consented. Groups had similar baseline characteristics. The average age was 66.7+/-9.94 years old. There were no statistically significant differences in baseline characteristic (Table 1). Majority of patients underwent anterior colporrhaphy or colpocleisis. There were no differences in terms of intraoperative blood loss, operative time, anesthetic modalities, opioid use, and complications (Table 2). Intention-to-treat analysis (n=68), the overall POUR rate was 31.2%. The POUR rate of the conventional group was 18.2% higher than the early removal group; however, it was not statistically significant. (32.4% vs. 26.5%, RR = 0.82; 95% CI:0.39-1.72). There was no significant difference between groups in terms of postoperative AB rate (14.7 vs 0%, p = 0.05). There was no postoperative UTI developed. In the early removal group, there are shorter lengths of hospital stay (1 day vs. 3 days) and 3.8hours earlier in time to ambulation (p = 0.2), without significant differences in postoperative patient satisfaction. The mean PGI-I were similar in both groups,(p = 0.58), mostly reported "much better"(Table 3). Even though patients experienced POUR, they were still satisfied with the outcome ( 80% vs 87.5% in POUR and non-POUR patients; p = 0.465, respectively). Conclusion(s): Among patients undergoing anterior compartment prolapse surgery with or without concomitant surgery, the early removal group is comparable in POUR rate to conventional group. There is a lesser chance of development of urinary tract infection and shorter length of hospitalization. Therefore, early transurethral catheter removal is preferable following anterior compartment prolapse surgery.

Chiofalo, B., et al. (2019). "Primary debulking surgery vs. interval debulking surgery for advanced ovarian cancer: review of the literature and meta-analysis." Minerva Medica 110(4): 330-340.
	Introduction: Epithelial ovarian cancer (EOC) is the seventh most common cancer among women in the world and the leading cause of death from gynecological malignancies. The standard treatment for advanced EOC consists of optimal primary debulking surgery (PDS) associated with an adjuvant chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) have been proposed in the management of advanced EOC to increase the rate of complete citoreductive surgery and to reduce morbidity and mortality. This systematic review and meta-analysis is conducted to compare the oncologic and postoperative outcomes of NACT and IDS with PDS followed by chemotherapy in patients with ovarian cancer.; Evidence Acquisition: We conducted a search on the electronic databases PubMed/Medline, Cochrane and Scopus. All randomized controlled trials, cohort and case-control studies comparing PDS and IDS in ovarian cancer published in English until 28 February 2019 were considered eligible.; Evidence Synthesis: Twenty studies were included in the systematic review. As regards the meta-analysis, only studies that allowed the data we needed to be extracted were included: five were included for the evaluation of overall survival (OS) and PFS and 9 for the evaluation of major postoperative complications and days of hospital stay.; Conclusions: From the meta-analysis of the current available literature, none of the two investigated procedures has proven to be superior in terms of OS and PFS in the treatment of advanced ovarian cancer. However surgical complexity and postoperative complications are reduced in the IDS group.

Chiou, Y., et al. (2023). "Effect of Perioperative Immunonutrition Intervention Among Gynecological Cancer Patients: A Systematic Review."
	
Chiu, C.-C., et al. (2022). "Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery - A Systematic Review and Network Meta-analysis." Journal of Minimally Invasive Gynecology 29(5): 602-612.
	Objective: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence.; Data Sources: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021.; Methods of Study Selection: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence.; Tabulation, Integration, and Results: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls.; Conclusion: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required. (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Chiyoda, T., et al. (2020). "Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis." Journal of Gynecologic Oncology 31(5): e67.
	Objective: To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC).; Methods: We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events.; Results: For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70-0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85-1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68-0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49-1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99-1.01); however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63-0.86).; Conclusions: Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Chiyoda, T., et al. (2022). "Sentinel node navigation surgery in cervical cancer: a systematic review and metaanalysis." International Journal of Clinical Oncology 27(8): 1247-1255.
	Sentinel node navigation surgery (SNNS) is used in clinical practice for the treatment of cervical cancer. This study aimed to elucidate the appropriate sentinel lymph node (SLN) mapping method and assess the safety and benefits of SNNS. We searched the PubMed, Ichushi, and Cochrane Library databases for randomized controlled trials (RCT) and studies on SLN in cervical cancer from January 2012 to December 2020. Two authors independently assessed study quality and extracted data. We quantitatively analyzed the detection rate, sensitivity/specificity, and complications and reviewed information, including the survival data of SLN biopsy (SLNB) without pelvic lymphadenectomy (PLND). The detection rate of SLN mapping in the unilateral pelvis was median 95.7% and 100% and in the bilateral pelvis was median 80.4% and 90% for technetium-99 m (Tc) with/without blue dye (Tc w/wo BD) and indocyanine green (ICG) alone, respectively. The sensitivity and specificity of each tracer were high; the area under the curve of each tracer was 0.988 (Tc w/wo BD), 0.931 (BD w/wo Tc), 0.966 (ICG), and 0.977 (carbon nanoparticle). Morbidities including lymphedema, neurological symptoms and blood loss were associated with PLND. One RCT and five studies all showed SNNS without systematic PLND does not impair recurrence or survival in early-stage cervical cancer with a tumor size ≤ 2-4 cm. Both Tc w/wo BD and ICG are appropriate SLN tracers. SNNS can reduce the morbidities associated with PLND without affecting disease progression in early-stage cervical cancer. (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Chloe, S., et al. (2023). "A systematic review and meta-analysis investigating the efficacy of intravenous immunoglobulin therapy in the treatment of secondary recurrent miscarriage."
	
Cho, J. S., et al. (2021). "Effects of Perioperative Dexmedetomidine on Immunomodulation in Uterine Cancer Surgery: A Randomized, Controlled Trial." Frontiers in Oncology 11: 749003.
	OBJECTIVE: Dexmedetomidine has sympatholytic, anti-inflammatory, and analgesic effects and may exert anti-tumor effect by acting on α2A adrenoreceptor. We investigated whether perioperative dexmedetomidine preserves immune function in patients undergoing uterine cancer surgery. METHODS: One hundred patients were randomly assigned to the control or dexmedetomidine groups (50 patients each). Dexmedetomidine was infused at rates of 0.4 μg/kg/h intraoperatively and 0.15 μg/kg/h during the first 24 h postoperatively. The primary outcome was natural killer (NK) cell activity, which was measured preoperatively and 1, 3, and 5 days postoperatively. The inflammatory response was measured by interleukin-6, interferon-γ, and neutrophil/lymphocyte ratio, and pain scores and opioid consumption were assessed. Cancer recurrence or metastasis and death were evaluated 2 years postoperatively. RESULTS: NK cell activity decreased postoperatively in both groups and changes over time were not different between groups (P=0.496). Interferon-γ increased postoperatively in the dexmedetomidine group, whereas it maintained at the baseline value in the control group. Change in interferon-γ differed significantly between groups (P=0.003). Changes in interleukin-6 and neutrophil-lymphocyte ratio were comparable between groups. Both pain score with activity during the first 1 h and opioid consumption during the first 1-24 h postoperatively were lower in the dexmedetomidine group. Rates of cancer recurrence/metastasis (16.3% vs. 8.7%, P=0.227) and death within 2 years postoperatively (6.7% vs. 2.2%, P=0.318) were not different between groups. CONCLUSIONS: Perioperative dexmedetomidine had no favorable impacts on NK cell activity, inflammatory responses, or prognosis, whereas it increased interferon-γ and reduced early postoperative pain severity and opioid consumption in uterine cancer surgery patients.

Cho, K. and M. Kim (2023). "Effects of aromatherapy on depression: A meta-analysis of randomized controlled trials." General Hospital Psychiatry 84: 215-225.
	Objective: Non-pharmacological interventions, such as aromatherapy, have been utilized for treating depression. This systematic review and meta-analysis aimed to investigate the effects of aromatherapy on depressive symptoms.; Method: The databases of PubMed, MEDLINE, CINAHL, EMBASE, Web of Science, and the Cochrane Library were searched from May 5, 2023, to May 20, 2023. Only randomized controlled trials that implemented aromatherapy in adults aged ≥18 years were included. The standardized mean difference (SMD) was calculated, and subgroup analysis, meta-ANOVA, and meta-regression were performed for the moderator variables.; Results: Thirty-two clinical trials (27 studies) were included in the final analysis. Aromatherapy demonstrated a moderate effect size for reducing depressive symptoms (SMD = -0.56, 95% CI: -0.69 to -0.43). Inhalation was the most effective method of delivery and blended essential oils were more effective than lavender or other single essential oils. Aromatherapy demonstrated a moderate effect size for reducing depressive symptoms among menopausal women, patients with heart disease (coronary artery disease or acute coronary syndrome), and psychological illnesses. However, it demonstrated no effect on postpartum or pregnant women. Mean age was a significant moderator variable.; Conclusions: Reliable evidence is present for the application of aromatherapy to reduce depressive symptoms, and it can be utilized effectively to decrease depressive symptoms.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Choi, S.-J. and D.-I. Kim (2019). "To evaluate the efficacy and safety of PLC in perimenopausal or postmenopausal women with Hot Flashes: study protocol for a randomized controlled trial." Trials 20(1): 415.
	Background: Hot flashes are the most frequent symptoms of the menopause, with 10-20% of all postmenopausal women reporting nearly intolerable occurrences. Although pharmacopuncture with hominis placenta extract is one of the new acupuncture therapies popular in East Asian medicine with a known efficacy in treating facial flushing, there has been little research on the efficacy and safety of this extract. This study, therefore, aims to evaluate the efficacy and safety of pharmacopuncture with hominis placenta extract (PLC) compared to injections of normal saline, in perimenopausal and postmenopausal women in Korea.; Methods/design: This study is a randomized placebo-controlled single-blind multi-center parallel-design trial. In total, 128 perimenopausal or postmenopausal women who meet the inclusion criteria will be recruited. The treatment group will receive PLC pharmacopuncture twice a week, for a total of 18 sessions over 9 weeks. The control group will receive injections of normal saline at the same acupoints during the same period. The post-treatment follow-up assessment will occur 4 weeks after the participant has completed the treatment.; Discussion: We believe that this trial will provide evidence for the efficacy and safety of PLC pharmacopuncture as a treatment for hot flashes in perimenopausal and postmenopausal women.; Trial Registration: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0003533 , Registered on 20 February 2019.

Choi, W., et al. (2023). "Phase 1 trial of 4-1BB-based adoptive T-cell therapy targeting human telomerase reverse transcriptase in patients with advanced refractory solid tumors." Cytotherapy 25(11): 1236-1241.
	Background aims: Human telomerase reverse transcriptase (hTERT) is an attractive target for anti-cancer therapies. We developed an effective method for generating hTERT-specific CD8+ T cells (hTERT-induced natural T cells [TERTiNTs]) using peripheral blood mononuclear cells (PBMCs) from patients with solid cancers and investigated their feasibility and safety. Method(s): This was a single-center phase 1 trial using a 3 + 3 dose escalation design to evaluate six dose levels of TERTiNTs. PBMCs from each patient were screened using an hTERT peptide panel to select those that stimulated CD8+ T cells. The four most stimulatory peptides were used to produce autologous CD8+ T cells from patients refractory or intolerant to standard therapies. Eligible patients received a single intravenous infusion of TERTiNTs at different dose levels (4 x 108 cells/m2, 8 x 108 cells/m2 and 16 x 108 cells/m2). Pre-conditioning chemotherapy, including cyclophosphamide alone or in combination with fludarabine, was administered to induce lymphodepletion. Result(s): From January 2014 to October 2019, a total of 24 patients with a median of three prior lines of therapy were enrolled. The most common adverse events were lymphopenia (79.2%), nausea (58.3%) and neutropenia (54.2%), mostly caused by pre-conditioning chemotherapy. The TERTiNT infusion was well tolerated, and dose-limiting toxicities were not observed. None of the patients showed objective responses. Seven patients (30.4%) achieved stable disease with a median progression-free survival of 3.9 months (range, 3.2-11.3). At the highest dose level (16 x 108 cells/m2), four of five patients showed disease stabilization. Conclusion(s): The generation of TERTiNTs was feasible and safe and provided an interesting disease control rate in heavily pre-treated cancer patients.Copyright © 2023 International Society for Cell & Gene Therapy

Chopra, S., et al. (2021). "Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 39(33): 3682-3692.
	PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Chou, H. H., et al. (2021). "Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: a phase II AGOG/TGOG trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 262: 13‐20.
	OBJECTIVE: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose‐dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. STUDY DESIGN: This phase II clinical trial using Simon's minimax two‐stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study‐defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3‐4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m2) (dose‐dense) plus 3‐weekly carboplatin (AUC5‐6) or 3‐weekly conventional schedule. After IDS, postoperative dose‐dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3‐weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3‐weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles. RESULTS: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study‐defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression‐free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7‐30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8‐64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study‐defined significant AEs of bowel perforation, poor‐healing wound, and hypertension were found in 1 case each, respectively. CONCLUSION: This phase II trial demonstrated adding bevacizumab to dose‐dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose‐dense scheduling throughout.

Choudhary, N., et al. (2022). "Hypericin and its anticancer effects: From mechanism of action to potential therapeutic application." Phytomedicine : international journal of phytotherapy and phytopharmacology 105: 154356.
	Background: Emerging studies indicate that hypericin has diverse pharmacological actions and exhibits potential for treatment of various types of cancer.; Purpose: The current review evaluates the pharmacological activity, associated molecular mechanism, and therapeutic application of hypericin as an anticancer agent according to the most recent state of knowledge with special emphasis on clinical trials and safety profile.; Method: This review follows The Preferred Reporting Items for Systematic Reviews criteria. Various databases, including PubMed, Scopus and Science Direct, were used to search and collect relevant literature. The major keywords used included the following: cancer, distribution, property, signaling pathway, pharmacological effect, treatment, prevention, in vitro and in vivo studies, toxicity, bioavailability, and clinical trials.; Results: One hundred three articles met the established inclusion and exclusion criteria. Hypericin has shown anticancer activity against the expansion of several cell types including breast cancer, cervical cancer, colorectal cancer, colon cancer, hepatocellular carcinoma, stomach carcinoma, leukemia, lung cancer, melanoma, and glioblastoma cancer. Hypericin exerts its anticancer activity by inhibiting pro-inflammatory mediators, endothelial growth factor, fibroblast growth factor, cell adhesion, angiogenesis, and mitochondrial thioredoxin. It has also been shown to cause an increase in the levels of caspase-3 and caspase-4, arrest the cell cycle at metaphase leading to cancer cell apoptosis, and affect various protein and gene expression patterns.; Conclusion: Hypericin exhibits significant inhibitory activity against various types of in vitro and in vivo cancer models. However, well-designed, high quality, large-scale and multi-center randomized clinical studies are required to establish the safety and clinical utility of hypericin in cancer patients. (Copyright © 2022. Published by Elsevier GmbH.)

Chow, B., et al. (2019). "Radiobiological dose calculation parameters for cervix cancer brachytherapy: A systematic review." Brachytherapy 18(4): 546-558.
	The GEC-ESTRO recommendation in cervical cancer treatment planning, including external beam radiotherapy and brachytherapy boosts, is to use radiobiological dose calculations. Such calculations utilize the linear-quadratic model to estimate the effect of multiple cellular response factors and dose delivery parameters. The radiobiological parameters utilized in these calculations are literature values estimated based on clinical and experimental results. However, the impact of the uncertainties associated with these parameters is often not fully appreciated. This review includes a summary of the radiobiological dose calculation (for both high-dose-rate and pulsed-dose-rate brachytherapy boost treatments) for cervical cancer and a compilation of the reported values of the associated parameters. As discrepancies exist between conventionally recommended and published values, equivalencies between current brachytherapy boosts may be imprecise and could create underappreciated uncertainties in the radiobiological dose calculations. This review highlights these uncertainties by calculating the radiobiological dose delivered by the brachytherapy boost when assuming different radiobiological parameter values (within the range reported by previous research). Furthermore, conventional treatment planning does not consider the effects of proliferation of the tumor over the treatment time, which can significantly decrease its radiobiological dose and can introduce an additional variance of over 7 Gy 10 . Further investigation of uncertainties in parameter values and modifications of current dose models could improve the accuracy of radiobiological dose calculation. (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Chow, H., et al. (2024). "A systematic review of community pharmacy interventions to improve peri- and post-menopausal health." Post Reproductive Health.
	Menopause is defined as the permanent cessation of menstruation due to loss of ovarian follicular function. Symptoms include mood disorders, vaginal atrophy, hot flashes and night sweats and can emerge during a gradual transition period called perimenopause. Community pharmacies are well placed to deliver a wide range of healthcare services, including supporting and educating menopausal women; however, to date, no systematic review has assessed the effectiveness of community pharmacy-led interventions in improving peri- and post-menopausal health. In accordance with PRISMA guidelines we evaluated community pharmacy-led interventions that targeted women in peri- or post-menopause. Electronic searches in EMBASE, MEDLINE, CINAHL and Cochrane Library were conducted on 13th February 2023. Additionally, we examined the included studies references and citation lists using Google Scholar. A total of 915 articles were identified and screened against the inclusion criteria. Two studies were included; one identified post-menopausal women at risk of developing osteoporosis (OP), and one evaluated the outcomes of a community pharmacy-based menopause education programme. Study one found 11 (11%) post-menopausal women were at risk of developing OP based on quantitative ultrasound screening offered by community pharmacists and referred to their physician. Study two reported that women had access to adequate personalised menopause counselling and increased knowledge of menopause topics because of the educational programme within community pharmacies. Both studies were of low quality. The lack of included studies reflects the need for high-quality research to determine whether community pharmacy-led interventions are feasible, effective and acceptable, to improve health outcomes of peri- or post-menopausal women.Copyright © The Author(s) 2024.

Chow Ka, M., et al. (2022). "A nurse-led sexual rehabilitation programme for rebuilding sexuality and intimacy after treatment for gynaecological cancer: Study protocol for a randomized controlled trial." Journal of Advanced Nursing 78(5): 1503-1512.
	Aim: To implement a nurse-led sexual rehabilitation programme for gynaecological cancer (GC) survivors and to evaluate its effects on their sexual functioning, sexual distress and marital satisfaction.; Design: An assessor-blinded, randomized controlled trial.; Methods: The development of the nurse-led sexual rehabilitation intervention was guided by the concept of sexual health, as stated in the Neotheoretical Framework of Sexuality; the explicit permission giving, limited information, specific suggestions and intensive therapy model; and evidence-based nursing interventions for sexuality. Four intervention sessions will be delivered along the treatment trajectory. Women newly diagnosed (within 3 months) with GC will be recruited from the gynaecological units of three hospitals in Hong Kong. The participants (N = 172) will be randomly assigned to the intervention group to receive the nurse-led sexual rehabilitation programme, or to an attention control group to receive attention on four occasions during the same period when the intervention group receives the intervention. Sexual functioning, sexual distress and marital quality will be measured at baseline, 1 month after the completion of cancer treatment, after completion of the sexual rehabilitation programme and 12 months after cancer treatment. Semi-structured interviews will be conducted with the participants in the intervention group to explore their experiences with and feelings towards the programme. The study was funded in March 2019 and ethics approval was obtained in January 2019.; Discussion: Positive outcomes of the nurse-led sexual rehabilitation programme will contribute to scientific and practical knowledge about nursing interventions to help GC survivors and their partners to resume a satisfying intimate relationship and adapt to changes in sexuality after treatment.; Impact: This study will contribute to the evidence for and advance research on the effectiveness of nurse-led sexuality rehabilitation interventions to support women and their partners to rebuild sexuality and intimacy after treatment for GC. (© 2022 John Wiley & Sons Ltd.)

Chowdhury, M. H., et al. (2020). "Effect of supplementary omega-3 fatty acids on pregnant women with complications and pregnancy outcomes: review from literature." Journal of Maternal-Fetal and Neonatal Medicine: 1-17.
	Numerous benefits have been associated with omega-3 fatty acid consumption during pregnancy and the postpartum period, whether it is consumed in the diet with seafood or via supplements such as fish oil. This review primarily aimed to assess the current situation of the impact of omega-3 long-chain Poly Unsaturated Fatty Acid (PUFA) supplementation on the outcomes of pregnancy. The electronic search of Medline, PubMed, Public Library of Science (PLOS) and Google Scholar databases was carried out for papers from 01 February 1995 to 01 March 2017 using keywords such as "pregnancy," "supplement," "long-chain polyunsaturated fatty acids," "omega 3 fatty acids," and "clinical trials." Out of twenty-six studies, both observational and interventional, fourteen studies found the influence of omega 3 fatty acids during pregnancy or the early postpartum period on the duration of gestation and infant size at birth, preeclampsia, depression, and infant visual function and neurodevelopment have been reported. Omega 3 fatty acid intakes (both in terms of absolute amounts of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and the ratio of these 2 fatty acids) varied widely in these studies, however, and no clear consensus exists regarding the effects of omega 3 fatty acids on any of these outcomes. Because of the potential importance of these fatty acids for pregnant or lactating women, fetus, and newborn infants and the limited data from clinical trials assessing the effect of these fatty acids on pregnancy and infant outcomes, additional research is required to better define optimal intakes of specific omega 3 fatty acids during these critical periods.Copyright © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Chowdhury, M. L., et al. (2019). "Urethral Pain Syndrome: A Systematic Review." Current Bladder Dysfunction Reports 14(2): 75-82.
	Purpose of Review: Urethral pain syndrome (UPS) is defined as pain localized to the urethra with an unpleasant sensation, dysuria often accompanied by urinary frequency and urgency present greater than 6 months in the absence of an identifiable cause. A paucity of information exists on the subject as it is often combined with conditions such as interstitial cystitis or prostatitis. The aim is to provide and explain different definitions and diagnostic work-up and discuss treatment options for providers. Recent Findings: Few recent studies exist addressing urethral pain syndrome. Most literature is decades old. Thirty-five full-text articles were included in the review. This syndrome occurs most commonly in females of childbearing age. Patients must be evaluated thoroughly with full history and physical. Etiologies proposed include sensory dysfunction, pelvic floor dysfunction, psychogenic factors (depression and anxiety), diet, obstruction, infections, and hypoestrogen status. Treatment strategies include behavioral management of stress management, diet modification, pelvic floor treatments, local estrogen, anesthetic with or without cooling, oral medications for related lower urinary tract symptoms, or anxiolytics/antidepressants. Psychological support is recommended for these patients. Summary: UPS can have multiple etiologies and a multimodal therapy should be applied to these patients. Therapy should be individualized, oftentimes including concurrent therapy for overlapping conditions. Serious pathology should be ruled out and a stepwise approach to treatment should be utilized after setting treatment expectations with the patient.Copyright © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Christelle, K., et al. (2020). "The effects of evening-primrose oil on menopausal symptoms: A systematic review and meta-analysis of randomized controlled trials." Current Women's Health Reviews 16(4): 265-276.
	Background: Evening primrose oil (EPO) has been a treatment option for reducing menopausal symptoms, but evidence for its use is inadequate. Objective(s): The study aimed to determine the effectiveness of EPO in treating menopausal symptoms among peri and postmenopausal women. Study Design: This is a systematic review with meta-analyses of randomised clinical trials (RCTs). Method(s): We searched CENTRAL, Medline, Embase and trial registries for relevant RCTs. The methodology and reporting were carried out grounded on references from the Cochrane collaboration and the preferred reporting items for systematic reviews and meta-analyses statement. Review Manager version 5.3.5 was used to perform all the statistical analyses. Result(s): Five RCTs, recruiting a total of 402 peri and postmenopausal women were identified. EPO did not reduce the frequency of daily vasomotor symptoms (MD 0.01 episodes, 95% CI-0.54 to 0.57, P=0.960), frequency of daytime hot flash episodes (MD-0.51 episodes, 95% CI-2.05 to 1.03, P=0.510), frequency of night sweat episodes (MD 0.33 episodes, 95% CI-0.48 to 1.13, P=0.430) and severity of vasomotor symptoms (SMD-0.45, 95% CI-1.56 to 0.66, P=0.420) in comparison to control. EPO was associated with a minimal reduction in the severity of overall menopausal symptoms in comparison to control (SMD-1.18; 95% CI-2.18 to-0.18, P=0.02). There were insufficient data to pool results for musculoskeletal symptoms, mood, sexuality, sleeping disorders and quality of life. Conclusion(s): EPO may reduce the severity of overall menopausal symptoms but is not effective to reduce the frequency and severity of vasomotor symptoms. The evidence quality ranged from very low to moderate. Further research is needed to enhance related evidence. PROSPERO Registration Number: CRD42019142821.Copyright © 2020 Bentham Science Publishers.

Christiansen Mille, G., et al. (2022). "SystematiC nurse-led cONsultations based oN Electronic patient-reported outcome among women with ovarian- or endometrial Cancer during chemoTherapy - protocol for the CONNECT study." Acta oncologica (Stockholm, Sweden) 61(5): 602-607.
	
Christiansen Ole, B., et al. (2019). "Treatment with intravenous immunoglobulin in patients with recurrent pregnancy loss: An update." Journal of Reproductive Immunology 133: 37-42.
	Intravenous immunoglobulin (IVIg) has a documented clinical effect in many autoimmune diseases and has so far been tested in >10 randomised controlled trials (RCTs) in women with recurrent pregnancy loss (RPL). The results of the RCTs have, however, been very divergent. In meta-analyses of all trials, no significant impact on live birth rate has been reported. In contrast, in sensitivity analyses, IVIg significantly increased live birth rates when initiated prior to conception and it had a borderline significant therapeutic effect in women with secondary RPL. Higher dosages of IVIg and serological signs of autoimmunity in the treated patients tended to increase the success rate after treatment. A follow-up study of patients from our recent RCT also supports a significant therapeutic effect in patients who had received IVIg before conception. The lessons learned from the published trials and meta-analyses should be incorporated in the design of future RCTs of IVIg in the treatment of RPL. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Christine, L., et al. (2021). "Behavioural interventions for peri and postmenopausal sleep disruption and insomnia: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Christmas Monica, M., et al. (2023). "Menopause hormone therapy and urinary symptoms: a systematic review." Menopause (New York, N.Y.) 30(6): 672-685.
	Importance: Urogenital changes associated with menopause are now classified as genitourinary syndrome of menopause (GSM), which includes symptoms of urgency, frequency, dysuria, and recurrent urinary tract infections for which the recommended treatment is estrogen. However, the association between menopause and urinary symptoms and the efficacy of hormone therapy for these symptoms is uncertain.; Objective: Our objective was to define the relationship between menopause and urinary symptoms including dysuria, urgency, frequency, recurrent urinary tract infections (UTIs), and urge and stress incontinence by conducting a systematic review of the effects of hormone therapy (HT) for urinary symptoms in perimenopausal and postmenopausal women.; Evidence Review: Eligible studies included randomized control trials with perimenopausal and postmenopausal women with a primary or secondary outcome of the following urinary symptoms: dysuria, frequent UTI, urgency, frequency, and incontinence, included at least one treatment arm of estrogen therapy, and were in English. Animal trials, cancer studies and pharmacokinetic studies, secondary analyses, and conference abstracts were excluded. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched until April 2022. Two authors reviewed each article with discrepancies resolved through whole group consensus. Data extracted included the following: publication date, country, setting, subject number, follow-up, duration, age, race/ethnicity, study design, inclusion criteria, and main findings.; Findings: There is insufficient evidence to confirm that menopause is associated with urinary symptoms. The effect of HT on urinary symptoms depends on type. Systemic HT may cause urinary incontinence or worsen existing urinary symptoms. Vaginal estrogen improves dysuria, frequency, urge and stress incontinence, and recurrent UTI in menopausal women.; Conclusions and Relevance: Vaginal estrogen improves urinary symptoms and decreases the risk of recurrent UTI in postmenopausal women.; Competing Interests: Financial disclosure/conflicts of interest: M.M.C. reports Board of Trustees for The North American Menopause Society (NAMS), NAMS Scientific Program Committee, NAMS Editorial Board, and FDA Bone, Reproductive and Urologic Division (BRUDAC) Committee. M.M.C. developed a menopause lecture series for AllianceChicago and wrote a white paper on GSM for Materna Medical, but did not receive any financial compensation. J.L. is a consultant for Haitec Medical, Inc. The other authors have nothing to disclose. (Copyright © 2023 by The North American Menopause Society.)

Christoffel, L., et al. (2021). "Transcervical Radiofrequency Ablation of Uterine Fibroids Global Registry (SAGE): Study Protocol and Preliminary Results." Medical devices (Auckland, N.Z.) 14: 77-84.
	Background: Transcervical fibroid ablation (TFA) is a minimally invasive, effective treatment of symptomatic uterine fibroids that utilizes intrauterine ultrasound for imaging and radiofrequency energy for ablation. Outcomes reported with TFA have been positive, with significant reductions in fibroid volume, improvements in symptom severity and health-related quality of life, and low complication and surgical reintervention rates. The SAGE registry characterizes the long-term (5-year) outcomes of TFA when used to treat symptomatic uterine fibroids in real-world usage.; Methods/design: SAGE is an ongoing postmarket global registry involving up to 50 sites and up to 500 women who select TFA with the Sonata system for treatment of symptomatic uterine fibroids. Patients are followed for 5 years. Main outcomes include symptom severity score and health-related quality of life subscales of the UFS-QoL, general health status on the EQ-5D, perceived treatment benefit, treatment satisfaction, work and activity patterns, overall patient treatment outcome, adverse events, pregnancy incidence and outcomes, and surgical reinterventions for heavy menstrual bleeding.; Discussion: The SAGE registry represents the largest known study of TFA for uterine fibroids and will generate up to 2500 patient-years of outcome data. Preliminary results from the first 160 treated women suggest broad applicability of TFA to a wide range of fibroid types and sizes and an excellent safety profile, with a device-related adverse event rate of 0.6% and a serious procedure-related adverse event rate of 0.6%. Of the 241 fibroids treated, 10% were submucous, 52% transmural, 28% intramural, and 10% subserous. Ablated fibroid diameters ranged from <1 cm to >10 cm, with 27% of fibroids having maximum diameters >5 cm. The real-world experience from SAGE will strengthen the existing evidence on the durability of TFA in providing meaningful relief from uterine fibroid symptoms and will have important clinical and economic implications for patients, physicians, and healthcare payers.; Trial Registration: https://clinicaltrials.gov, NCT03118037. Registered on 18 April 2017.; Competing Interests: The authors report no competing interests. (© 2021 Christoffel et al.)

Christopoulou, A., et al. (2022). "Prophylaxis of cancer-associated venous thromboembolism with low-molecular-weight heparin-tinzaparin: Real world evidence." Oncology Letters 23(4): 115.
	Thromboprophylaxis, as a preventive measure for cancer-associated thrombosis (CAT), may be beneficial for patients with active cancer and high-risk for thrombosis. The present post hoc analysis include a total of 407 patients enrolled in the Greek Management of Thrombosis study, who received thromboprophylaxis with tinzaparin. The objectives of the present analysis were: i) To obtain sufficient evidence for the administration of prophylaxis in patients with active cancer, irrespective of Khorana risk assessment model score; ii) to identify the selection criteria for both dose and duration of tinzaparin; and iii) to evaluate the efficacy and safety of tinzaparin administered for CAT prophylaxis. The main tumor types for the patients included in the present study were as follows: Lung (25.1%), pancreatic (14.3%), breast (9.1%), stomach (8.4%), colorectal (7.9%) and ovarian (7.6%). Furthermore, metastatic disease was observed in 69.5% of the patients. High thrombotic burden agents (HTBAs) were administered to 66.3% of the patients, and 17.4% received erythropoietin. A total of 43.7% of the patients exhibited a Khorana score <2. The results of the present study demonstrated that both the presence of metastatic disease and the use of HTBAs seemed to influence oncologists' decisions for the use of thromboprophylaxis in patients with active cancer, regardless of Khorana score. Tinzaparin, in dose expressed in the standard notation for heparins, i.e., anti-Xa factor international units (Anti-Xa IU), was administered at an intermediate dose (InterD; 8,000-12,000 Anti-Xa IU; once daily) to 52.4% of patients, while the remaining patients received a prophylactic dose (ProD; ≤4,500 Anti-Xa IU; once daily). The average duration of thromoprophylaxis was 5 months. Furthermore, a total of 14 (3.4%) thrombotic events and 6 (1.5%) minor bleeding events were recorded. A total of four thrombotic events were observed following an InterD treatment of tinzaparin, while 10 thrombotic events were observed following ProD treatment. The present study also demonstrated that an InterD of tinzaparin was administered more frequently to patients with a body mass index >30 kg/m 2 , a history of smoking and a history of metastatic disease, along with administration of erythropoietin. InterD tinzaparin treatment was found to be potentially more efficacious and without safety concerns. The present study is a registered clinical trial (ClinicalTrials.gov code, NCT03292107; registration date, September 25, 2017).; Competing Interests: The authors declare that they have no competing interests. (Copyright: © Christopoulou et al.)

Chrysanthopoulos, I., et al. (2023). "Detection of GSTM1 -null Genotype in Women Undergoing IVF Treatment." Journal of Clinical Medicine 12(23).
	Background: Glutathione S-transferase (GST) M1 belongs to a family of detoxification enzymes and deficiency in enzyme activity is due to a homozygous deletion of the GSTM1 gene. Several studies reveal a possible correlation between female infertility and GSTM1 polymorphisms. The aim of this study is to investigate the effect of the GSTM1 -null polymorphism in female infertility as well as in IVF parameters.; Methods: In the study group 125 women were classified as infertile according to WHO and 49 women with at least one successful pregnancy and no miscarriages, as control group. Genomic DNA from blood samples was isolated and PCR amplification was applied to determine the presence of GSTM1 -null genotype.; Results: Data analysis demonstrated a statistically significant higher presence of GSTM1 -null variant in the infertile group compared to the control group. In a subgroup analysis of the infertile group, the estradiol levels, the number of fertilized oocytes as well as the number and the quality of the cumulus-oocyte complex, were statistically significant higher in women detected with the wildtype of GSTM1 gene compared to those who had the GSTM1 null genotype (deletion).; Conclusions: Our study results propose a possible involvement of GMST1 in female infertility and may help elucidate possible interactions between the microenvironment of oocytes and the oxidative stress.

Chu, Z., et al. (2024). "Effects of different treatment methods on clinical efficacy and fertility outcomes of patients with adenomyosis." Journal of Ovarian Research 17(1): 16.
	Objective: This trial was to investigate the effect of different treatment methods on the clinical efficacy and fertility outcome of patients with adenomyosis. Method(s): In total, 140 patients with adenomyosis were evenly and randomly allocated into group A (laparoscopic surgery), group B (laparoscopic surgery combined with gonadotropin-releasing hormone analogs [GnRH-a]), group C (ultrasound-guided percutaneous radiofrequency ablation), and group D (ultrasound-guided percutaneous radiofrequency ablation combined with GnRH-a). On the 3rd day after surgery, patients in group B and group D were subcutaneously injected with GnRH-a (Leuprorelin Acetate SR for Injection) at 3.75 mg/time, once every 4 weeks, for a total of 3 months. The therapeutic effects of the 4 groups were compared, including menstrual volume, dysmenorrhea score, uterine volume, clinical efficacy, luteinizing hormone (LH), estradiol (E2), and follicle-stimulating hormone (FSH) levels, CA125 levels, recurrence, pregnancy status, and pregnancy outcomes. Result(s): After treatment, the menstrual volume of 4 groups was lowered, dysmenorrhea, Visual Analog Scale (VAS) score, LH, FSH, E2, and CA125 levels were reduced, and uterine volume was decreased. The menstrual volume, VAS score, levels of LH, FSH, E2, and CA125, and uterine volume were reduced in groups B, C, and D compared with group A, and the decrease was more significant in group D. The total effective rate of group D was 100.00%, which was higher than that of group A (71.43%), group B (80.00%), and group C (82.86%). After one year of drug withdrawal, the recurrence of hypermenorrhea, dysmenorrhea, uterine enlargement, and excessive CA125 in group D was significantly lower than that in groups A, B and C, and the recurrence in groups B and C was significantly lower than that in group A (P < 0.05). Compared with groups A, B, and C, group D had a higher pregnancy rate, natural pregnancy rate, and lower in vitro fertilization-embryo transfer rate (P < 0.05), but showed no significant difference in pregnancy outcomes. Conclusion(s): Ultrasound-guided percutaneous radiofrequency ablation combined with Leuprorelin Acetate is effective in the treatment of adenomyosis, which can effectively relieve clinical symptoms, protect postoperative ovarian function, reduce recurrence rate, alleviate pain, and improve quality of life.Copyright © 2024, The Author(s).

Chua, V. H., et al. (2022). "Quality of Life among Survivors of Locally Advanced Cervical Cancer Treated with Definitive Chemoradiotherapy in a Decade of Transition." Asian Journal of Oncology 8(2): 81-91.
	Introduction The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiotherapy (CRT). External beam radiotherapy (EBRT) and brachytherapy (BRT) advances in the last decade have resulted in improved local control and survival. There is a lack of data on quality of life (QoL) among survivors. Objective This systematic review aimed to synthesize published data on QoL among LACC survivors treated with CRT and determine clinical factors of QoL. Methods Systematic literature search was conducted in PubMed, EBSCO, and ScienceDirect for relevant articles published in 2010 to 2020. Eligible studies on LACC survivors aged 18 years and above, who reported QoL after CRT, were included. Screening and data extraction were done by two pairs of independent reviewers. Results Five cohort studies, three cross sectional studies, and one clinical trial were included. Reported temporal evolution of QoL varied: two studies reported improvement of overall QoL, while four reported worsening of symptoms. Gastrointestinal, genitourinary, sexual, and psychosocial domains showed significant impairment. Age, stage, and baseline distress and physical condition were clinical determinants of body image, sexual activity, menopausal symptoms, distress, and dyspnea. Peripheral neuropathy, lymphedema, and dyspnea were reported, while grade 3 to 4 gastrointestinal, genitourinary, and musculoskeletal toxicities were rare. Conclusion Use of advanced EBRT and BRT techniques is associated with improving QoL in the first 3 years from treatment completion. Gastrointestinal, genitourinary, sexual, and psychosocial functions remain impaired on the long-term. Other late toxicities worth noting include peripheral neuropathy, lower limb edema, and insufficiency fractures.Copyright © 2022. Spring Hope Cancer Foundation & Young Oncologist Group of Asia. All rights reserved.

Chudzicka-Strugała, I., et al. (2021). "Effects of Synbiotic Supplementation and Lifestyle Modifications on Women With Polycystic Ovary Syndrome." The Journal of Clinical Endocrinology and Metabolism 106(9): 2566-2573.
	CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. OBJECTIVE: This study was designed to evaluate effects of lifestyle modifications and synbiotic supplementation on PCOS. DESIGN: A randomized (1:1) double-blind, placebo-controlled trial. SETTING: Academic hospital. PATIENTS OR OTHER PARTICIPANTS: Overweight and obese women with PCOS were identified according to the Rotterdam criteria. Evaluations were performed at baseline and repeated after 3 months of treatment. INTERVENTION: Lifestyle modifications in combination with synbiotic supplementation or placebo. MAIN OUTCOME MEASURES: Change in body mass index (BMI) and testosterone level. RESULTS: In the placebo group, a 5% decrease in BMI was accompanied by significant decreases of the waist, hip, and thigh circumferences. The synbiotic group experienced an 8% decrease in BMI, which was significantly greater than that in the control group (P = 0.03) and was accompanied by decreases in the waist, hip, and thigh circumferences. Testosterone did not decrease significantly in the placebo group (decrease of 6%), whereas in the synbiotic group it decreased by 32% (P < 0.0001). The decrease of testosterone was significantly greater in the synbiotic group than in the placebo group (P = 0.016). CONCLUSIONS: Synbiotic supplementation potentiated effects of lifestyle modifications on weight loss and led to significant reduction of serum testosterone.

Chui, C., et al. (2021). "Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery– A Systematic Review and Network Meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Chung Jacqueline Pui, W., et al. (2022). "Hyoscine butylbromide in pain reduction associated with ultrasound-guided manual vacuum aspiration: a randomized placebo-controlled trial." Reproductive Biomedicine Online 44(2): 295-303.
	Research Question: What is the effect of adding an anti-spasmodic drug to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss?; Design: Double-blind, placebo-controlled, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions.; Results: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[ 1108 ] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups.; Conclusions: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted. (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Chung, J. P. W., et al. (2021). "Ovarian reserve and recurrence 1 year post-operatively after using haemostatic sealant and bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy." Reproductive Biomedicine Online 43(2): 310-318.
	RESEARCH QUESTION: Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas? DESIGN: This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3-8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Müllerian hormone (AMH) and FSH concentrations, and reproductive outcomes. RESULTS: The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55-18.38). No difference in reproductive outcomes was found between the two groups. CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate.

Chun-Xi, Z., et al. (2021). "Does the addition of a low-quality embryo as part of double embryo transfer improve pregnancy outcome? a systematic review and network meta-analysis."
	
Cianci, S., et al. (2021). "Robotic Pelvic Exenteration for Gynecologic Malignancies, Anatomic Landmarks, and Surgical Steps: A Systematic Review." Frontiers in surgery 8: 790152.
	Pelvic exenteration represents the last resort procedure for patients with advanced primary or recurrent gynecological malignancy. Pelvic exenteration can be divided into different subgroup based on anatomical extension of the procedures. The growing application of the minimally invasive surgical approach unlocked new perspectives for gynecologic oncology surgery. Minimally invasive surgery may offer significant advantages in terms of perioperative outcomes. Since 2009, several Robotic Assisted Laparoscopic Pelvic Exenteration experiences have been described in literature. The advent of robotic surgery resulted in a new spur to the worldwide spread of minimally invasive pelvic exenteration. We present a review of the literature on robotic-assisted pelvic exenteration. The search was conducted using electronic databases from inception of each database through June 2021. 13 articles including 53 patients were included in this review. Anterior exenteration was pursued in 42 patients (79.2%), 2 patients underwent posterior exenteration (3.8%), while 9 patients (17%) were subjected to total exenteration. The most common urinary reconstruction was non-continent urinary diversion (90.2%). Among the 11 women who underwent to total or posterior exenteration, 8 (72.7%) received a terminal colostomy. Conversion to laparotomy was required in two cases due to intraoperative vascular injury. Complications' report was available for 51 patients. Fifteen Dindo Grade 2 complications occurred in 11 patients (21.6%), and 14 grade 3 complications were registered in 13 patients (25.5%). Only grade 4 complications were reported (2%). In 88% of women, the resection margins were negative. Pelvic exenteration represents a salvage procedure in patients with recurrent or persistent gynecological cancers often after radiotherapy. A careful patient selection remains the milestone of such a mutilating surgery. The introduction of the minimally invasive approach has led to advantages in terms of perioperative outcomes compared to classic open surgery. This review shows the feasibility of robotic pelvic exenteration. An important step forward should be to investigate the potential equivalence between robotic approaches and the laparotomic one, in terms of long-term oncological outcomes.

Cianci, S., et al. (2022). "Surgical outcomes of diaphragmatic resection during cytoreductive surgery for advanced gynecological ovarian neoplasia: A randomized single center clinical trial - DRAGON." Gynecologic Oncology 164(2): 271-277.
	Introduction: Ovarian cancer (OC) represent nearly 4% of gynecologic malignancies and it is often diagnosed at advanced stage. Diaphragmatic surgery, a fundamental step of advanced stage ovarian cancer (ASOC) debulking surgery, is associated with a high post-operative complication incidence, which is supposedly reduced with thoracostomy tube placement. We assessed the role of intra-operative thoracostomy tube placement, as a prevention measure for post-operative complications, after diaphragmatic resection.; Methods: This was a single center prospective randomized trial. Ovarian cancer patients, who underwent mono-lateral diaphragmatic resection, were randomized 1:1 into two arms. Arm A included patients receiving intra-operative thoracostomy tube placement (TP); Arm B patients did not receive thoracostomy tube placement (NTP). After surgery, all patients underwent seriate chest x-ray and ultrasound to record thoracic complications. Statistical analysis included uni- and multivariable logistic regression model (proportional odds model).; Results: Three hundred seventy-one patients were screened and 88 patients were enrolled: 44 in arm A and B, respectively. No statistically significant differences for intra-operative (p = 0.291) and any grade of post-operative complication (p = 0.072) were detected, while 6.8% of patients in arm A and 22.7% in arm B experienced severe respiratory symptoms (p = 0.035); 18.2% of patients in arm A had a moderate/large pleural effusion versus 65.9% in arm B (p < 0.0001). At multivariable analysis, results confirmed that the NTP-group had a higher risk to receive post-operative thoracostomy tube placement due to pleural effusion than the TP-group (odds ratio [95% Confidence Interval] = 14.5 [3.7-57.4]).; Conclusions: Thoracostomy intra-operative tube placement after diaphragmatic resection is effective to prevent post-operative thoracic complications. The extension of resection does not influence outcomes and the risk of post-operative thoracentesis or TP remain elevated.; Competing Interests: Declaration of Competing Interest Authors declare to have nothing to disclose. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cianci, S., et al. (2023). "Exploring Surgical Strategies for Uterine Fibroid Treatment: A Comprehensive Review of Literature on Open and Minimally Invasive Approaches." Medicina (Kaunas, Lithuania) 60(1).
	Background and Objectives: Uterine myomas represent one of the most prevalent pathologies affecting the female population. These benign neoplasms originate from the smooth muscular cells of the uterus, and they can be either single or multiple. Often associated with debilitating symptoms such as pelvic heaviness, pain, constipation, and urinary dysfunctions, the surgical management of myomectomy exhibits considerable variability. This diversity in approaches is influenced by factors such as the number and size of myomas, the patient's age, and overall clinical conditions. This study aims to elucidate and compare the advantages and disadvantages of different surgical approaches, specifically endoscopic procedures versus open surgery, providing valuable insights for clinical decision making. Materials and Methods: A comprehensive bibliographic search spanning from 2013 to 2023 was systematically conducted across databases including Medline, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search utilized keywords such as "myomectomy laparoscopic and open", "myomectomy open and minimally invasive", "myomectomy open and laparoscopic", and "myomectomy open vs. laparoscopic." The research methodology, along with predetermined inclusion and exclusion criteria, was established prior to the search, ensuring a systematic and rigorous approach. Subsequently, data analysis was carried out. Results: Following the study selection process, 25 articles met the eligibility criteria for inclusion in this analysis. The average numbers of myomas were 3.7 (ranging from 1 to 13.7) and 5.4 (ranging from 1 to 13.5) for the minimally invasive surgery and open surgery groups, respectively. In terms of myoma size, the total averages across studies were 7 cm (ranging from 4.8 to 14) for the minimally invasive group and 8 cm (ranging from 3.9 to 11.2) for the open surgery group. The average pregnancy and delivery rates were 29.7% (ranging from 1.8 to 100) for the minimally invasive group and 28.5% (ranging from 1.8 to 100) for the open surgery group. Regarding complications, the average rate was 14.2% (ranging from 0 to 50) for the endoscopic group and 22.3% (ranging from 0 to 60.3) for the laparotomic group. Conclusions: In conclusion, a critical factor influencing the choice of surgical approach is primarily the size and quantity of fibroids. The mini-laparotomic approach emerges as a viable alternative to endoscopy, demonstrating favorable surgical outcomes and aesthetic results. Interestingly, the type of surgical procedure appears to have no significant impact on the pregnancy rate.; Competing Interests: All authors declare no conflicts of interest.

Cianci, S., et al. (2021). "Percutaneous-assisted vs mini-laparoscopic hysterectomy: comparison of ultra-minimally invasive approaches." Updates in surgery 73(6): 2347-2354.
	To assess the feasibility and the safety of the ultra-minimally invasive (U-MIS) approaches in gynecology, we compared our experience in percutaneous assisted hysterectomy (PSS-H) with a series of 3 mm mini-laparoscopy hysterectomy (m-LPS-H). 126 patients affected by benign and malignant gynecological conditions were considered eligible for minimally invasive hysterectomy: 80 patients received PSS approach and 46 m-LPS approach. For both groups, we evaluated intra and perioperative outcomes, post-operative pain and cosmetic outcomes. The baseline characteristics were comparable between the two study groups. As well, no differences were reported in the clinical indications for hysterectomy, principally fibroids/adenomyosis, endometrial hyperplasia and early stage endometrial cancer. The median operative time was 88.5 (40-190) minutes for PSS-H group and 95.0 (42-231) minutes in m-LPS-H group (p=0.131). No differences were detected in median estimated blood loss (p=0.104) as well, in the uterine manipulator usage (p=0.127) between the two different surgical approaches. Only 1 (2.2%) conversion to standard laparoscopy occurred in m-LPS-H group (p=0.691). One intra-operative complication was recorded 1 (1.3%) in the PSS-H group (p=0.367). The post-operative early complication was recorded in five cases of PSS-H group (p=0.158), none for m-LPS-H procedures. The results in post-operative pain detection was statistically significant after 4 h in favor of m-LPS-H group (p=0.001). After 30 days no differences in cosmetic satisfaction were detected between the two groups (p=0.206). PSS-H and m-LPS-H are two valid U-MIS alternatives for benign gynecological conditions and low/intermediate risk endometrial cancer.Copyright © 2020. Italian Society of Surgery (SIC).

Ciavattini, A., et al. (2021). "The Impact of 9-Valent HPV Vaccination on Couple Infertility Prevention: A Comprehensive Review." Frontiers in Medicine 8: 700792.
	A comprehensive literature review was performed to determine the relationship between HPV infection and infertility and the eventual role of the 9-valent vaccine for infertility prevention. The search was extended from January 1997 through July 2021. Data collected from selected articles focused on three main topics: statistical associations between HPV prevalence and assisted reproductive technology (ART) outcome, association between HPV and characteristics of semen, and associations between HPV and miscarriage. Articles that identified HPV genotypes were selected for this review to study the possible role of the 9-valent vaccine in infertility prevention. To date, there is no agreement on the implication HPV female infection has on the fertility and miscarriage rate. Although it can be stated that HPV prevalence among couples with infertility undergoing ART treatment is consistent, it does not seem to affect the performance of oocytes. Otherwise, HPV infection affects sperm parameters, in particular spermatozoa motility. When an association can be found, most cases of HR-HPV involved are those included in the 9-valent vaccine. The correlation between HPV male infection both with asthenozoospermia and increased risk of pregnancy loss could recommend the extension of anti-HPV vaccination to adolescent males along with cancer prevention. Despite the fact that the relation between 9-valent HPV genotypes involved in female infection and miscarriage/infertility is not clear, the impact of this virus on health reproduction is evident. Considering this, the importance of HPV vaccination in adolescent females is confirmed. A vaccine efficacy study could be useful to confirm the importance of primary prevention for couple reproductive health.© Copyright © 2021 Ciavattini, Marconi, Giannella, Delli Carpini, Sopracordevole and Di Giuseppe.

Cibralic, S., et al. (2022). "The impact of midwifery continuity of care on maternal mental health: A narrative systematic review." Midwifery 116: 103546.
	BACKGROUND: Systematic reviews have shown that midwifery continuity of care programs lead to improvements in birth outcomes for women and babies, but no reviews have focused specifically on the impact of midwifery continuity of care on maternal mental health outcomes. OBJECTIVE: To systematically review the available evidence on the impact of midwifery continuity of care on maternal mental health during the perinatal period. METHOD: A systematic search of published literature available through to March 2021 was conducted. A narrative approach was used to examine and synthesise the literature. RESULTS: The search yielded eight articles that were grouped based on the mental health conditions they examined: fear of birth, anxiety, and depression. Findings indicate that midwifery continuity of care leads to improvements in maternal anxiety/worry and depression during the perinatal period. CONCLUSION: There is preliminary evidence showing that midwifery continuity of care is beneficial in reducing anxiety/worry and depression in pregnant women during the antenatal period. As the evidence stands, midwifery continuity of care may be a preventative intervention to reduce maternal anxiety/worry and depression during the perinatal period.

Cibula, D., et al. (2019). "A prospective multicenter trial on sentinel lymph node biopsy in patients with early-stage cervical cancer (SENTIX)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29(1): 212-215.
	Objective: Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stage cervical cancer. It appears in guidelines as an alternative option to systematic pelvic lymphadenectomy. The evidence about safety is, however, based mostly on retrospective studies, in which SLN was combined with systematic lymphadenectomy.; Materials and Methods: SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy. The primary end point is recurrence rate; the secondary end point is the prevalence of lower-leg lymphedema and symptomatic pelvic lymphocele. The reference recurrence rate was set up conservatively at 7% at 24 months after treatment. With a sample size of 300 patients treated per protocol, the trial is powered to detect a non-inferiority margin of 5% (90% power, p = 0.05) for recurrence rate, 30% reduction in the prevalence of symptomatic lymphocele or lower-leg lymphedema, with reference rates of 30% and 6% at 12 months (p = 0.025, Bonferroni correction). The patients eligible for SENTIX have stage IA1/LVSI+, IA2, IB1 (<2 cm for fertility sparing), with negative LN on pre-operative imaging. Intra-operatively, patients are excluded when there is a failure to detect SLN on both sides of the pelvis in cases of more advanced cancer (stage >IB1), or a positive intra-operative SLN assessment. The quality of SLN pathology evaluation will be assessed by central review. Three interim safety analyses are pre-planned when 30, 60, 150 patients complete 12 months' follow-up.; Conclusions: The first patient was enrolled into the study in June 2016 and, by June 2018, 340 patients had been enrolled. The first analysis of secondary outcomes should be available in 2019 and the oncological outcome of 300 patients at the end of 2021. The trial is registered as a CEEGOG trial (CEEGOG CX-01), ENGOT trial (ENGOT-Cx 2), and at the ClinicalTrials.gov database (NCT02494063).; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Cibula, D., et al. (2021). "Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial." Gynecologic Oncology 162(3): 652-660.
	OBJECTIVE: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. METHODS: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). RESULTS: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. CONCLUSIONS: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

Cibula, D., et al. (2023). "ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 184: 109682.
	In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.; Competing Interests: Declaration of competing interests CCh has reported advisory boards for GSK, MSD and EISAI; SFL has reported advisory boards for MSD, GSK, AstraZeneca and Novartis; DL has reported consultant honoria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen and PharmaMar, advisory boards for AstraZeneca, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept and Sutro, research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar, research sponsored by AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Roche, Seagen and Novartis, and speakers’ bureau activities for AstraZeneca, Clovis Oncology, GSK, MSD and PharmaMar; UM has reported advisory boards for AstraZeneca (Steering committee member for CALLA Study); RN has reported research grants from Elekta, Varian, Accuray, Dutch Research Council, and Dutch Cancer Society; AO has reported personal fees for advisory board membersip from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, F. Hoffmann-La Roche, Genmab/Seagen, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de Espana, SA, Mersana Thereapeutics, Novocure, PharmaMar, piIME Oncology, Roche, Sattucklabs, Sutro Biopharma and Tesaro, and personal fees for travel/accomodation from AstraZeneca, PharmaMar and Roche; DQ has reported advisory boards for Mimark inc; MPS has reported research grants and personal fees for workshops from Elekta AB; DC, MRR, FP, CC, AF, DF, DJK, FJ, CK, PM, RN, FPec, JP, SR, AS, VS, KT, IZ and JCL have reported no conflicts of interest. (Copyright © 2023 ESGO, ESTRO, ESP. Published by Elsevier B.V. All rights reserved.)

Cicogna, S., et al. (2023). "Aggressive Angiomyxoma of the Lower Female Genital Tract in Pregnancy: A Review of the MITO Rare Tumors Group." Cancers 15(13): 3403.
	Deep (aggressive) angiomyxoma of the lower genital tract is a rare malignancy affecting women of reproductive age. Being a hormone-sensitive tumor, its growth is particularly benefitted during pregnancy. Surgical excision with complete resection is indicated, even if a wait-and-see approach can be considered until delivery, to avoid destructive surgeries. The mode of delivery is to be evaluated based on the location and size of the neoplasm; vaginal delivery is not contraindicated, as long as the tumor does not obstruct the birth canal. Positive surgical margins are the most important prognostic factor for recurrence. Adjuvant therapy with gonadotropin-releasing hormone analogues may be proposed after pregnancy, in the case of non-radical surgery. Despite the high local relapse rate, the outcomes for mother and child are favorable. Since recurrences can occur after many years, the patient should be included in long-term follow-up.Copyright © 2023 by the authors.

Cimadomo, D., et al. (2023). "ESHRE good practice recommendations on recurrent implantation failure." Human Reproduction Open 2023(3): hoad023.
	STUDY QUESTION: How should recurrent implantation failure (RIF) in patients undergoing ART be defined and managed? SUMMARY ANSWER: This is the first ESHRE good practice recommendations paper providing a definition for RIF together with recommendations on how to investigate causes and contributing factors, and how to improve the chances of a pregnancy. WHAT IS KNOWN ALREADY: RIF is a challenge in the ART clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rationale or with unequivocal evidence of benefit. STUDY DESIGN, SIZE, DURATION: This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, and the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focussing on 'recurrent reproductive failure', 'recurrent implantation failure', and 'repeated implantation failure'. PARTICIPANTS/MATERIALS, SETTING, METHODS: The ESHRE Working Group on Recurrent Implantation Failure included eight members representing the ESHRE Special Interest Groups for Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the working group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then open to ESHRE members for online peer review and was revised in light of the comments received. MAIN RESULTS AND THE ROLE OF CHANCE: The working group recommends considering RIF as a secondary phenomenon of ART, as it can only be observed in patients undergoing IVF, and that the following description of RIF be adopted: 'RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions'. It was agreed that the recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Recommendations were colour-coded based on whether the investigations/interventions were recommended (green), to be considered (orange), or not recommended, i.e. not to be offered routinely (red). LIMITATIONS, REASONS FOR CAUTION: While awaiting the results of further studies and trials, the ESHRE Working Group on Recurrent Implantation Failure recommends identifying RIF based on the chance of successful implantation for the individual patient or couple and to restrict investigations and treatments to those supported by a clear rationale and data indicating their likely benefit. WIDER IMPLICATIONS OF THE FINDINGS: This article provides not only good practice advice but also highlights the investigations and interventions that need further research. This research, when well-conducted, will be key to making progress in the clinical management of RIF. Copyright © 2023 The Author(s).

Cina, A., et al. (2022). "Optimizing the Angiography Protocol to Reduce Radiation Dose in Uterine Artery Embolization: The Impact of Digital Subtraction Angiographies on Radiation Exposure." Cardiovascular and interventional radiology 45(2): 249-254.
	Purpose: The aim was to compare a protocol of uterine artery embolization (UAE) consisting in three digital subtraction angiographies (DSAs)-Group A, with a protocol based on a single DSA-Group B.; Materials and Methods: This is a single-center prospective randomized study enrolling 20 women (mean age 41 years, range 22-55 years) with uterine fibroids treated with UAE, from January 2015 to February 2016. All UAEs were performed by two interventional radiologists using the same angiography machine. Protocol of Group A consisted in three DSA runs (non-selective pelvic view and selective uterine views before and after embolization). Protocol of Group B consisted in 1 DSA run: selective UA angiography before embolization. (Fluoroscopic roadmap was used for UA catheterization; fluoroscopy storage was used as control after embolization.) Each patient was randomized to receive Protocol A in one pelvic side and Protocol B on the other.; Results: All patients received bilateral UAE. Mean fluoroscopy time for UA catheterization was 11.3 ± 3.7 s. (Protocol A) and 9.93 ± 2.99 s. (Protocol B) (p = 0.19). Fluoroscopy dose for catheterization and embolization was not different between both protocols (p = 0.14). Identification of the UA origin score was similar in both protocols (median error = 0, p = 0.79). Mean dose area product (DAP) was 40859 mGy/cm 2 (Protocol A) and 28839 mGy/cm 2 (Protocol B) (p = 0.003). Mean effective dose (ED) decreased from Protocol A (14.6 mSv) to Protocol B (9.2 mSv; - 37%). Mean absorbed dose (AD) to ovaries and uterus, respectively, decreased of 53% and 55% from Protocol A to Protocol B.; Conclusion: Reducing the number of DSA runs from 3 to 1 during UAE allows at least a 30% reduction on radiation exposure, without compromising technical outcomes. (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Cincione, I. R., et al. (2023). "Short-time effects of ketogenic diet or modestly hypocaloric Mediterranean diet on overweight and obese women with polycystic ovary syndrome." Journal of endocrinological investigation 46(4): 769-777.
	Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterized clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardio-vascular and metabolic sequelae, including diabetes and metabolic syndrome. In light of these evidences, the most therapeutic option prescribed to PCOS women with obesity, regardless of the phenotype from the severity of clinical expression, is lifestyle correction by diet and physical activity.; Purpose: The aim of this study was to evaluate the association between PCOS with KD in overweight and/or obese women with PCOS, and evaluate the possible beneficial effects on metabolic and endocrine parameters, compared to a standard, balanced hypocaloric diet such as Mediterranean diet (MD).; Methods: Participants were assigned to receive, in a 1:1 ratio, one of the two following dietary sequences: KD or MD. In all subjects anthropometric parameters, body composition and metabolic and endocrine parameters were obtained at baseline and after dietetic treatment.; Results: Our results showed a significant change in the anthropometric and biochemical parameters in both groups after both diet therapies, with statistically significant differences (p < 0.001). Though, the reductions of all parameters were significantly greater in KD group than in MD group.; Conclusion: Our results suggest that a reduction of dietary intake of carbohydrates by KD may be considered as a valuable non-pharmacological treatment for PCOS. (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Cincione, R. I., et al. (2021). "Effects of Mixed of a Ketogenic Diet in Overweight and Obese Women with Polycystic Ovary Syndrome." International Journal of Environmental Research and Public Health 18(23).
	Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardiovascular and metabolic sequelae, including diabetes and metabolic syndrome. The relationship between central obesity and the development of insulin resistance is widely verified. Adipose tissue excess and the coexistent dysregulation of adipocyte functions directly contribute to the pathogenesis of the metabolic complications observed in women with PCOS. In the light of these evidence, the most therapeutic option prescribed to obese women with PCOS, regardless of the phenotype e from the severity of clinical expression, is lifestyle correction by diet and physical activity. The aim of this study is to evaluate the beneficial effects of ketogenic diet in 17 obese women with PCOS. Our results showed that the ketogenic diet inducing therapeutic ketosis, improves the anthropometric and many biochemical parameters such as LH, FSH, SHBG, insulin sensitivity and HOMA index. In addition, it induces a reduction in androgenic production, whereas the contextual reduction of fat mass reduced the acyclic production of estrogens deriving from the aromatization in the adipose tissue of the androgenic excess, with an improvement of the LH/FSH ratio. This is the first study on the effects of the ketogenic diet on PCOS, however, further studies are needed to elucidate the mechanism underlying ketogenic diet effects.

Cirino, N. H. and J. M. Knapp (2019). "Perinatal Posttraumatic Stress Disorder: A Review of Risk Factors, Diagnosis, and Treatment." Obstetrical and Gynecological Survey 74(6): 369-376.
	Importance Perinatal posttraumatic stress disorder (P-PTSD) occurs in approximately 3% to 15% of women in the postpartum period. It is often underrecognized, poorly characterized, and undertreated. If untreated, it can lead to maternal and infant morbidity. Objective The aim of this review article is to discuss P-PTSD as it relates to the obstetrician gynecologist, focusing specifically on identifying perinatal risk factors, P-PTSD diagnostic tools, and treatment options. Evidence Acquisition PubMed, PsycINFO, Cochrane Library, and Scopus were searched on MeSH terms and free text for terms related specifically to P-PTSD. Because of the lack of data on treatment specifically for the perinatal population, a second search for general PTSD treatment guidelines was conducted and incorporated into this review. Results Risk factors have been identified in the literature in 4 major categories: obstetric, psychiatric, social, and subjective distress during delivery. Two diagnostic tests, the general PTSD diagnostic tool, the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the specific diagnostic tool, the Perinatal Post-Traumatic Stress Disorder Questionnaire, can both be helpful for the clinician to diagnose patients who may have P-PTSD. Individual trauma-focused psychotherapy is first line for treatment of P-PTSD. Immediate debriefing interventions and non-trauma-focused psychotherapy has not been shown to be helpful. If trauma-focused psychotherapy is not available or not preferred, selective serotonin reuptake inhibitors and non-trauma-focused psychotherapy can be used. Conclusions and Relevance Identifying and treating P-PTSD have important implications for maternal and neonatal health. Few treatment studies exist for P-PTSD specifically, so combining P-PTSD research with current guidelines for PTSD is necessary to inform clinical practice. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After participating in this CME activity, the participant should be better able to identify several risk factors for the development of PTSD in the perinatal period; describe 2 diagnostic tools to help diagnose and monitor P-PTSD; and compare effective and ineffective treatment options for perinatal PTSD, recognizing the importance of timing of interventions.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Clamp Andrew, R., et al. (2022). "Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial." The Lancet. Oncology 23(7): 919-930.
	Background: Standard-of-care first-line chemotherapy for epithelial ovarian cancer is carboplatin and paclitaxel administered once every 3 weeks. The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin. However, this benefit was not observed in the previously reported progression-free survival results of ICON8. Here, we present the final coprimary outcomes of overall survival and updated progression-free survival analyses of ICON8.; Methods: In this open-label, randomised, controlled, phase 3 trial (ICON8), women aged 18 years or older with newly diagnosed stage IC-IV epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (here collectively termed ovarian cancer, as defined by International Federation of Gynecology and Obstetrics [FIGO] 1988 criteria) and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 117 hospitals with oncology departments in the UK, Australia and New Zealand, Mexico, South Korea, and Ireland. Patients could enter the trial after immediate primary surgery (IPS) or with planned delayed primary surgery (DPS) during chemotherapy, or could have no planned surgery. Participants were randomly assigned (1:1:1), using the Medical Research Council Clinical Trials Unit at University College London randomisation line with stratification by Gynecologic Cancer Intergroup group, FIGO disease stage, and outcome and timing of surgery, to either 3-weekly carboplatin area under the curve (AUC)5 or AUC6 and 3-weekly paclitaxel 175 mg/m 2 (control; group 1), 3-weekly carboplatin AUC5 or AUC6 and weekly paclitaxel 80 mg/m 2 (group 2), or weekly carboplatin AUC2 and weekly paclitaxel 80 mg/m 2 (group 3), all administered via intravenous infusion for a total of six 21-day cycles. Coprimary outcomes were progression-free survival and overall survival, with comparisons done between group 2 and group 1, and group 3 and group 1, in the intention-to-treat population. Safety was assessed in all patients who started at least one chemotherapy cycle. The trial is registered on ClinicalTrials.gov, NCT01654146, and ISRCTN registry, ISRCTN10356387, and is closed to accrual.; Findings: Between June 6, 2011, and Nov 28, 2014, 1566 patients were randomly assigned to group 1 (n=522), group 2 (n=523), or group 3 (n=521). The median age was 62 years (IQR 54-68), 1073 (69%) of 1566 patients had high-grade serous carcinoma, 1119 (71%) had stage IIIC-IV disease, and 745 (48%) had IPS. As of data cutoff (March 31, 2020), with a median follow-up of 69 months (IQR 61-75), no significant difference in overall survival was observed in either comparison: median overall survival of 47·4 months (95% CI 43·1-54·8) in group 1, 54·8 months (46·6-61·6) in group 2, and 53·4 months (49·2-59·6) in group 3 (group 2 vs group 1: hazard ratio 0·87 [97·5% CI 0·73-1·05]; group 3 vs group 1: 0·91 [0·76-1·09]). No significant difference was observed for progression-free survival in either comparison and evidence of non-proportional hazards was seen (p=0·037), with restricted mean survival time of 23·9 months (97·5% CI 22·1-25·6) in group 1, 25·3 months (23·6-27·1) in group 2, and 24·8 months (23·0-26·5) in group 3. The most common grade 3-4 adverse events were reduced neutrophil count (78 [15%] of 511 patients in group 1, 183 [36%] of 514 in group 2, and 154 [30%] of 513 in group 3), reduced white blood cell count (22 [4%] in group 1, 80 [16%] in group 2, and 71 [14%] in group 3), and anaemia (26 [5%] in group 1, 66 [13%] in group 2, and 24 [5%] in group 3). No new serious adverse events were reported. Seven treatment-related deaths were reported (two in group 1, four in group 2, and one in group 3).; Interpretation: In our cohort of predominantly European women with epithelial ovarian cancer, we found that first-line weekly dose-dense chemotherapy did not improve overall or progression-free survival compared with standard 3-weekly chemotherapy and should not be used part of standard multimodality front-line therapy in this patient group.; Funding: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.; Competing Interests: Declarations of interests ARC reports institutional funding from Cancer Research UK for the present Article, consulting fees from AstraZeneca, payment or honoraria for lectures and presentations from Clovis Oncology and AstraZeneca, and support for attending meetings from GSK/Tesaro. IAM reports consulting fees from Clovis Oncology, AstraZeneca, GSK/Tesaro, and Roche; honoraria for lectures of presentations from AstraZeneca and GSK; travel support for attending meetings from AstraZeneca and GSK; and participation on an Independent Data Monitoring Committee for Transgene. SBl reports consulting fees from Ellipses Pharma, Theolytics, Amphista, and RApport Global Strategic Services; honoraria for lectures or presentations from Nucana and the Norwegian Cancer Society; has a planned patent (WO1999062548A90); being a member of advisory boards for the UCB6114, TORCH, AVAT-M, MROC, and OCTOVA studies; being founder and treasurer of La-Related Protein Society; and has received institutional support to conduct clinical trials from Nucana, UCB, Nurix, Astex, BergenBio, MSD, Redx, and MiNA Therapeutics. JBr reports royalties from Inivata; consulting fees from AstraZeneca; payment or honoraria for lectures or presentations from GSK and AstraZeneca; holding two patents that have been issued (1818159.5 and 1818159.4); being a cofounder and shareholder of Tailor Bio; and being a previous cofounder and shareholder of Inivata. TJP reports consulting fees from AstraZeneca, Exact Health, and MSD, and support for attending meetings from Gilead. SS reports honoraria for lectures or presentations from AstraZeneca and MSD, participation in advisory board meetings for AstraZeneca, and is current President of the British Gynaecological Cancer Society. RL reports advisory works for and honoraria for educational events and support for travel and enrolment at conferences from AstraZeneca and GSK. MH reports consulting fees and payment or honoraria for lectures or presentations from GSK and Clovis Oncology. SBa reports grants from AstraZeneca, Tesaro, and GSK; consulting fees from Amgen, AstraZeneca, Genmabs, GSK, Immunogen, MSD, Merck Sereno, Mersana, Oncxerna, Seagen, and Shattuck Labs; payment or honoraria for lectures from Amgen, AstraZeneca, Clovis Oncology, GSK, Immunogen, MSD, Mersana, Pfizer, Roche, and Takeda; and is European Society for Medical Oncology (ESMO) Director of Membership. RMG reports grants from Clovis Oncology, Boehringer Ingelheim, and Lily/Ignyta; consulting fees from Clovis Oncology, AstraZeneca, MSD, GSK, Sotio, Immunogen, and Novartis; payment or honoraria for lectures or presentations from Clovis Oncology, AstraZeneca, and GSK; support for attending conferences from GSK; being a member of the Independent Data Monitoring Committee for the Glasgow Cancer Research Trials Unit and Swiss GO Trials Group; and receipt of equipment (drugs) to institution from GSK. CLH reports royalties from Cambridge University Press, support for attending conferences from Tesaro, being chair of the Wales Cancer Network Gynaecological Cancer Site Group, and a member of British Gynaecological Society Guidelines Group. JAL reports institutional research grants from AstraZeneca and MSD/Merck; payment or honoraria for lectures or presentations from Pfizer, AstraZeneca, GSK, MSD, Clovis Oncology, Eisai, Bristol Myers Squibb, Artios Pharma, VBL Therapeutics, and Neopharm; being chair of an Independent Data Monitoring Committee for Regeneron; being editor of the Gynaecological Clinical Practice Guidelines (for ESMO); and former Vice President of European Society of Gynaecological Oncology. All other authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Clamp, A. R., et al. (2021). "Rucaparib maintenance treatment for recurrent ovarian carcinoma: the effects of progression-free interval and prior therapies on efficacy and safety in the randomized phase III trial ARIEL3." International Journal of Gynecological Cancer 31(7): 949‐958.
	INTRODUCTION: In ARIEL3 (NCT01968213), the poly(adenosine diphosphate‐ribose) polymerase inhibitor rucaparib significantly improved progression‐free survival versus placebo regardless of biomarker status when used as maintenance treatment for recurrent ovarian cancer. The aim of the current analyses was to evaluate the efficacy and safety of rucaparib in subgroups based on progression‐free interval following penultimate platinum, number of prior chemotherapies, and prior use of bevacizumab. METHODS: Patients were randomized 2:1 to rucaparib 600 mg twice daily or placebo. Within subgroups, progression‐free survival was assessed in prespecified, nested cohorts: BRCA‐mutant, homologous recombination deficient (BRCA‐mutant or wild‐type BRCA/high genomic loss of heterozygosity), and the intent‐to‐treat population. RESULTS: In the intent‐to‐treat population, median investigator‐assessed progression‐free survival was 8.2 months with rucaparib versus 4.1 months with placebo (n=151 vs n=76; HR 0.33, 95% CI 0.24 to 0.46, p<0.0001) for patients with progression‐free interval 6 to ≤12 months, and 13.6 versus 5.6 months (n=224 vs n=113; HR 0.39, 95% CI 0.30 to 0.52, p<0.0001) for those with progression‐free interval >12 months. Median progression‐free survival was 10.4 versus 5.4 months (n=231 vs n=124; HR 0.42, 95% CI 0.32 to 0.54, p<0.0001) for patients who had received two prior chemotherapies, and 11.1 versus 5.3 months (n=144 vs n=65; HR 0.28, 95% CI 0.19 to 0.41, p<0.0001) for those who had received ≥3 prior chemotherapies. Median progression‐free survival was 10.3 versus 5.4 months (n=83 vs n=43; HR 0.42, 95% CI 0.26 to 0.68, p=0.0004) for patients who had received prior bevacizumab, and 10.9 versus 5.4 months (n=292 vs n=146; HR 0.35, 95% CI 0.28 to 0.45, p<0.0001) for those who had not. Across subgroups, median progression‐free survival was also significantly longer with rucaparib versus placebo in the BRCA‐mutant and homologous recombination deficient cohorts. Safety was consistent across subgroups. CONCLUSIONS: Rucaparib maintenance treatment significantly improved progression‐free survival versus placebo irrespective of progression‐free interval following penultimate platinum, number of lines of prior chemotherapy, and previous use of bevacizumab.

Clapp, M. A., et al. (2024). "The Impact of a Behavioral-Economics Informed Intervention on Primary Care Utilization for Postpartum Individuals with Chronic Conditions: A Randomized Controlled Trial." MedRxiv.
	Importance: Despite careful monitoring of chronic and gestational conditions during pregnancy, most postpartum individuals with (or at high risk for) chronic conditions are not engaged in primary care following delivery. This lack of postpartum obstetric-to-primary care transition reflects a missed opportunity to improve short- and long-term health and well-being. Objective(s): To evaluate the efficacy of a behavioral economics-informed intervention designed to reduce patient administrative burden and information gaps on postpartum primary care visit completion. Design(s): Individual-level randomized controlled trial. Setting(s): Academic obstetric practice that included hospital- and community-based outpatient clinics. Participant(s): English- and Spanish-speaking pregnant or recently postpartum adults who had obesity (pre-pregnancy body mass index (>=30 kg/m2)), anxiety or depressive mood disorder, type 1 or 2 diabetes mellitus, chronic hypertension, gestational diabetes, and pregnancy-related hypertension listed in their medical record were eligible to participate. Participants also were required to have a primary care clinician (PCP) listed in their electronic health record. Intervention(s): A behavioral economics-informed intervention bundle, which included automatic scheduling of PCP appointments after delivery, patient-tailored health information, and appointment reminder nudges. Main Outcome: Attending a "health care maintenance" (i.e., "annual exam") appointment or receiving disease-specific management relating to the eligibility criteria (obesity, anxiety/depression, diabetes, or hypertension) by a PCP within 4 months of delivery. Result(s): 360 patients were randomized: 176 to the control group and 184 to the intervention group. primary outcome occurred in 22.0% in the control group and 40.0% in the intervention group (p<0.001). In the regression model that accounted for the randomization strata, the intervention increased PCP visit completion within 4 months of a patient's EDD by 19.9 percentage points (95% confidence interval (CI) 10.7-29.1). Conclusions and Relevance: Standard postpartum care practice encourages but does not facilitate transitions from obstetric to primary care. This study found that a behavioral science-informed intervention designed to facilitate this transition through default PCP visit scheduling, tailored messages, and nudge reminders substantially increased postpartum primary care visit completion for patients with or at risk for common comorbidities. This intervention represents a potentially low-cost and scalable solution to increase primary care engagement and ongoing health condition management after pregnancy, a time of high engagement and health activation. Trial Registration: NCT05543265.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Clara, B., et al. (2020). "Efficacy of phloroglucinol for the treatment of pain of gynaecologic or obstetrical origin: a systematic review of literature of randomised controlled trials." European Journal of Clinical Pharmacology 76(1): 1-6.
	Purpose: Antispasmodics like phloroglucinol are commonly used to alleviate pain. Various authorities recommend the use of this drug for conditions such as dysmenorrhoea, threatened abortion or labour pains. The goal was to carry out a systematic review analysing the existing data concerning the efficacy of phloroglucinol to treat pain in obstetrical or gynaecologic cases. The protocol was registered in Prospero (CRD 42018094065).; Methods: The keywords "phloroglucinol" and "randomised controlled trials" were used to search Medline, Embase and the Cochrane Library. We selected randomised, controlled against placebo trials testing the effect of phloroglucinol on gynaecologic or obstetrical pain either as a primary or secondary endpoint. We excluded trials exploring pain caused by intestinal, renal, metabolic or other causes and trials that were not available for critical review in either English or French. A quantitative synthesis (meta-analysis) was planned if the included trials were sufficiently homogenous. If this were not the case, a descriptive synthesis would be presented.; Results: Twelve trials identified studied the effect of phloroglucinol in gynaecologic or obstetrical conditions. Only two trials corresponded to the inclusion criteria of this review, one of which was not available for critical review.; Conclusions: Phloroglucinol is not well evaluated in this field. Whether for labour pains, abortion pains or benign gynaecologic pains, the results found are insufficient to promote the use of this drug in these indications.

Clark, K. and M. Westberg Sarah (2019). "Benefits of Levonorgestrel Intrauterine Device Use vs. Oral or Transdermal Progesterone for Postmenopausal Women Using Estrogen Containing Hormone Therapy." Innovations in pharmacy 10(3).
	Background: Endometrial hyperplasia is a major concern for women that start estrogen replacement therapy (ERT) to control symptoms experienced during perimenopause and postmenopause. Progesterone provides protection against endometrial hyperplasia, and there are multiple dosage forms of progesterone available. Intrauterine progesterone may offer an appealing option with additional benefits beyond endometrial protection for patients.; Objective: The overarching objective of this systematic review is to characterize the relationship between levonorgestrel containing intrauterine devices (LNG-IUD) and the prevention of endometrial hyperplasia in peri- and postmenopausal women. Specifically, this systematic review addresses whether LNG-IUD has equivalent efficacy of protecting against endometrial hyperplasia, but an improved safety profile when compared to oral progesterone in women using ERT.; Methods: OVID Medline, Scopus, and Cochrane were used to find available studies that have investigated the relationship between endometrial hyperplasia prevention and varying dosage forms of progesterone. Randomized control studies comparing LNG-IUD with no treatment, placebo, or other hormonal therapy in adult females were included. In addition, due to a lack of randomized control studies, four non-comparative studies were included.; Results: There were eleven total studies included that investigated LNG-IUD use in women on ERT. According to the studies, the LNG-IUD was equally effective as other routes (oral, vaginal) of progesterone administration in protecting against endometrial hyperplasia.; Conclusions: The LNG-IUD prevents endometrial proliferation at least as effective as oral or vaginal forms of progesterone. LNG-IUD is a safe option for women starting estrogen replacement therapy and has added benefits due to decreased adverse effects.; Competing Interests: Conflicts of interest: None (© Individual authors.)

Clark, L., et al. (2022). "Proper understanding of recurrent stress urinary incontinence treatment in women (PURSUIT): a randomised controlled trial of endoscopic and surgical treatment." Trials 23(1): 628.
	Background: Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently, the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment, and currently, there is no consensus on how best to treat women with recurrent, or persistent, SUI. Method(s): A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1 year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients' and clinicians' views and experiences of the interventions. Discussion(s): There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN12201059. Registered on 09 January 2020.Copyright © 2022, The Author(s).

Clark, L., et al. (2021). "The role of fitness trackers and tailored feedback messages in motivating endometrial cancer survivors to increase physical activity: results of the MOVES trial." Gynecologic Oncology 162: S304.
	Objectives: Endometrial cancer (EC) survivors are often overweight or obese and may benefit from increased physical activity. Increases in daily step count of 2,000 steps per day has been shown to improve cardiovascular health. We sought to assess a fitness intervention (fitness tracker + tailored feedback messages) for EC survivors. Methods: A prospective trial of EC survivors was undertaken from September 2018 to December 2019. Thirty‐nine survivors were approached for enrollment with 36 randomized (18 intervention, 18 control). All participants received a fitness tracker. Survivors were randomized 1:1 to receipt or non‐receipt of weekly tailored feedback messages. The primary outcome was change in average daily step count from baseline (week 1) to study completion (week 12). Secondary outcomes included acceptability, and changes in metabolic lab parameters (serum glucose, LDL, and insulin levels), body mass index (BMI) and waist to hip ratio (W/H). The trial was powered to detect a clinically significant change in daily step count of 2,000 steps. Comparisons of baseline to study completion labs were made using the Wilcoxon Two‐sample test. Student's T‐test was used for comparisons of control and intervention groups. Results: At baseline, there was no difference in BMI (35.9 vs 36.7, p=0.81) or W/H ratio (0.9 vs 0.89, p=0.40) between control and intervention arms. Baseline daily step count was 5291 steps in the control arm and 4295 in the intervention arm (p=0.16). There was no difference in baseline metabolic labs including glucose (100 vs 103, p=0.85), serum insulin (13.1 vs 16.8, p=0.78), and LDL (150 vs 113, p=0.07). The intervention group saw a statistical change in average daily step count (4295 to 5332, p=0.02). The control group did not have a statistically significant change (5291 to 5600, p=0.40). For the primary outcome of average daily step count change, there was no statistically significant difference between the two groups (+309 control vs +1037 intervention, p=0.21). There was no difference in change in BMI (‐0.27 vs ‐0.02, p=0.7), glucose (+1 vs ‐3, p=0.29), LDL (‐9.1 vs ‐3.5, p=0.95) or insulin (‐2.15 vs ‐1.95, p=0.32) between the control and intervention arms. Regarding acceptability, survivors found the feedback to be helpful (87%) and easy to understand (87%). Two‐thirds of survivors found the messages to be motivating, 47% desired increased frequency of messaging, and 53% thought the weekly message was adequate. Overall, 33% of intervention survivors versus 22% of control survivors had decline in fitness tracker use during the intervention, resulting in missing step data (p=0.46). Conclusions: A fitness intervention using fitness trackers and tailored feedback messaging may improve physical activity as measured by daily step count in EC survivors, however, significant noncompliance with fitness tracker use was seen in both groups by study end. Tailoring the frequency of feedback messages to survivor preference may be important to optimizing this intervention.

Clark, N. (2021). "Laparoscopic abdominal cerclage: an effective option for refractory cervical insufficiency." Contemporary ob/gyn 66(1): 18‐21.
	
Clarke, M., et al. (2021). "A silent burden-prolapse, incontinence, and infertility in Australian Aboriginal and Torres Strait Islander women: A systematic search and narrative review." International Journal of Gynecology and Obstetrics 155(2): 268-274.
	Background: Pelvic organ prolapse (POP), urinary incontinence, and infertility are all prevalent conditions associated with considerable reduction in quality of life. As a group, Aboriginal and Torres Strait Islander women may be at higher risk of these conditions, but studies are scarce. Objective(s): To review the literature pertaining to the epidemiology, diagnosis, and management of these conditions in Indigenous Australian women. Search strategy: Medline, Embase, and Scopus were searched for articles published between 1980 and 2021 pertaining to these conditions in Indigenous Australian women. Selection Criteria: Studies that did not directly address the epidemiology, diagnosis, and management of these conditions were excluded. Main Result(s): It was possible to identify only 11 papers dealing with these conditions in Indigenous Australian women. Only one dealt with POP and was a retrospective audit of a health outreach program in the Northern Territory concluding that there was significant underreporting of the condition. Five papers dealt with urinary incontinence and, again, described significant underreporting and poor referral pathways. Five papers reported small studies about infertility, one reporting poor engagement from clinical directors. Conclusion(s): It was concluded that despite the importance of these conditions, there is almost no body of research and this is an urgent national problem.Copyright © 2021 International Federation of Gynecology and Obstetrics

Classe, J.-M., et al. (2022). "CHRONO: randomized trial of the CHROnology of surgery after Neoadjuvant chemotherapy for Ovarian cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(8): 1071-1075.
	Background: In patients treated for advanced ovarian cancer not suitable for complete primary surgery, interval surgery after three courses of neoadjuvant chemotherapy has been considered standard management since the EORTC randomized trial published in 2010. An alternative approach with delayed surgery after six courses of neoadjuvant chemotherapy was reported in retrospective series.; Primary Objectives: To assess the efficacy on progression free survival of interval cytoreduction surgery after three cycles of neoadjuvant chemotherapy compared with delayed surgery after six cycles of neoadjuvant chemotherapy.; Study Hypothesis: In women with ovarian cancer not suitable for primary surgical cytoreduction, surgery after six cycles of neoadjuvant chemotherapy will prove better disease-free survival than cytoreductive surgery after only three cycles.; Trial Design: CHRONO is a multicenter, randomized phase III trial. After three courses of neoadjuvant chemotherapy, eligible patients will be randomized (1:1) to either completion surgery followed by an additional five cycles of chemotherapy (control arm) or an additional three cycles of neoadjuvant chemotherapy followed by completion surgery and then two additional cycles of chemotherapy (experimental arm). Patients in both groups will receive eight total cycles of chemotherapy.; Major Inclusion/exclusion Criteria: The main inclusion criteria are histologically confirmed epithelial high-grade serous or endometrioid ovarian cancer, documented FIGO stage IIIB-IVA unsuitable for complete primary surgery but considered resectable after three courses of neoadjuvant chemotherapy. The main exclusion criteria are mucinous, clear cell, carcinosarcoma, or low-grade serous histologies.; Primary Endpoint: The primary endpoint is progression-free survival.; Sample Size: 210 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2023. The estimated date for presentation of the first results is Q3 2028.; Trial Registration Number: NCT03579394.; Competing Interests: Competing interests: J-MC: lectures/other education events from Astra Zeneca, GSK, and Clovis. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Clayton, A. H., et al. (2024). "The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials." Journal of Affective Disorders 351: 904-914.
	Background: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). Method(s): Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (>=50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. Result(s): Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). Limitation(s): Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. Conclusion(s): Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.Copyright © 2024

Clifford, R. E., et al. (2021). "Metformin as a radiosensitiser for pelvic malignancy: A systematic review of the literature." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47(6): 1252-1257.
	Background: The treatment of pelvic malignancies has continued to improve over recent years, with neoadjuvant radiotherapy often considered the gold standard to downstage disease. Radiosensitisers are routinely employed in an attempt to improve response of cancers to radiotherapy. Previous preclinical evidence has suggested a role for metformin, a commonly used drug for type 2 diabetes.; Method: A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string 'Metformin' AND ('Radiosensitivity' OR 'radiosensitising' OR 'radiosensitising'). Additional papers were detected by scanning the references of relevant papers. Data were extracted from each study by two authors onto a dedicated proforma. The review was registered on the PROSPERO database (ID: CRD42020199066).; Results: A total of 242 papers were identified, 11 of which were included in this review; an additional 5 papers were obtained from reference searches. Metformin has been demonstrated to reduce cell-viability post-radiotherapy in both rectal and prostate cancer cell lines, with an enhanced effect in tumours with a p53 mutation and increased apoptosis post-radiotherapy for cervical cancer. Clinical trials demonstrate improved tumour and nodal downstaging and pCR rates for rectal cancer using metformin as a radiosensitiser.; Conclusion: With an increasing understanding of the underlying mechanism of the effects on metformin prospective studies are required to assess the effect of routine use on cancer related outcomes. Progressive future studies may be better served by the use of predictive biomarker guided treatment to enable identification of the appropriate cohort to target.; Competing Interests: Declaration of competing interest None. (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Climent Maria, T., et al. (2023). "Should We Abandon Intraperitoneal Chemotherapy in the Treatment of Advanced Ovarian Cancer? A Meta-Analysis." Journal of Personalized Medicine 13(12).
	Background: Ovarian cancer is the gynaecological malignancy with the highest mortality and diagnosis often occurs in its advanced stages. Standard treatment in these cases is based on complete cytoreductive surgery with adjuvant intravenous chemotherapy. Other types of treatment are being evaluated to improve the prognosis of these patients, including intraperitoneal chemotherapy and antiangiogenic therapy. These may improve survival or time to relapse in addition to intravenous chemotherapy.; Objective: The aim of this meta-analysis is to determine whether treatment with intravenous chemotherapy remains the gold standard, or whether the addition of intraperitoneal chemotherapy has a benefit in overall survival (OS) and disease-free interval (DFS).; Materials and Methods: A literature search was carried out in Pubmed and Cochrane, selecting clinical studies and systematic reviews published in the last 10 years. Statistical analysis was performed using the hazard ratio measure in the RevMan tool.; Results: Intraperitoneal chemotherapy shows a benefit in OS and DFS compared with standard intravenous chemotherapy. The significant differences in OS (HR: 0.81 CI 95% 0.74-0.88) and in DFS (HR: 0.81 CI 95% 0.75-0.87) are statistically significant ( p < 0.00001). There were no clinical differences in toxicity and side-effects.; Conclusion: Intraperitoneal chemotherapy is an option that improves OS and DFS without significant toxicity regarding the use of intravenous chemotherapy alone. However, prospective studies are needed to determine the optimal dose and treatment regimen that will maintain the benefits while minimising side effects and toxicity and the profile of patients who will benefit most from this treatment.

Climent Maria, T., et al. (2023). "Surgery in Recurrent Ovarian Cancer: A Meta-Analysis." Cancers 15(13).
	Background : The second cytoreductive surgery performed for a patient who has recurrent ovarian cancer remains controversial. Our study analyzes overall survival (OS) and disease-free survival (DFS) for cytoreductive surgery in addition to chemotherapy in recurrent ovarian cancer instead of chemotherapy alone. Methods : A meta-analysis was conducted using PubMed and the Cochrane database of systematic reviews to select randomized controlled studies. In total, three randomized studies were used, employing a total of 1249 patients. Results : The results of our meta-analysis of these randomized controlled trials identified significant differences in OS (HR = 0.83, IC 95% 0.70-0.99, p < 0.04) and DFS (HR = 0.63, IC 95% 0.55-0.72, p < 0.000001). A subgroup analysis comparing complete cytoreductive surgery and surgery with residual tumor achieved better results for both OS (HR = 0.65, IC 95% 0.49-0.86, p = 0.002) and DFS (HR = 0.67, IC 95% 0.53-0.82, p = 0.0008), with statistical significance. Conclusions : A complete secondary cytoreductive surgery (SCS) in recurrent ovarian cancer (ROC) demonstrates an improvement in the OS and DFS, and this benefit is most evident in cases where complete cytoreductive surgery is achieved. The challenge is the correct patient selection for secondary cytoreductive surgery to improve the results of this approach.

Clinkscales, N., et al. (2022). "The effectiveness of psychological interventions for anxiety in the perinatal period: A systematic review and meta-analysis." Psychology and psychotherapy 96(2).
	PURPOSE: Anxiety disorders are relatively common during pregnancy and the postnatal period. Despite their potential acceptability to users, psychological interventions research for this population is still in its infancy. The meta-analysis aimed to comprehensively evaluate the evidence of the effectiveness of psychological interventions for reducing perinatal anxiety. METHOD: The review followed PRISMA guidelines. A total of 26 studies published between 2004 and 2022 fulfilled inclusion criteria of which 22 were included in the meta-analysis. RESULTS: Results indicated that psychological interventions were more effective than control conditions in reducing symptoms of perinatal anxiety (equivalent to a medium post treatment effect size). Effect sizes were robust for cognitive, behavioural and mindfulness-based interventions. Targeting anxiety also appeared to impact on depression symptoms. There was substantial evidence of methodological heterogeneity. CONCLUSIONS: This review demonstrates that psychological interventions are effective in reducing symptoms of both anxiety and comorbid anxiety and depression in both the antenatal and postnatal periods. Further research on longer-term effects, infant outcomes, treatment approach and modality are required.

Close, A., et al. (2023). "Exclusive manual perineal rehabilitation with lidocaine 2% gel in the treatment of provoked vestibulodynia: results from a single-arm interventional study." International journal of impotence research 35(2): 157-163.
	As of now, there is no adequate therapeutic strategy for provoked vestibulodynia (PVD). Pelvic Floor Muscle Therapy (PFMT) is a widely used technique in general pelvic floor rehabilitation. The objective of this study is to examine the effects of exclusive manual perineal rehabilitation with lidocaine 2% gel on PVD. During the first session, recruited patients (n = 68; mean age 31 ± 8.6; range: 18-52) received a questionnaire (Q1) on general well-being and health, pain of the genital area, sexual function, and symptoms during vaginal penetration. This questionnaire was based on a generalised questionnaire on the quality of life, the Medical Outcomes Study 36-item (SF-36), the Female Sexual Function Index (FSFI), and the Visual Analogue Scale (VAS). A second identical questionnaire with an additional set of open-ended questions concerning the assessment of the treatment was collected after treatment (Q2). A total of 45 questionnaires were completed. Statistical results showed a significant improvement of all items before and after treatment (p < 0.001): perceived general well-being and health, perceived vulvar pain, perceived sexual function, and perceived vaginal penetration. In conclusion, exclusive manual perineal rehabilitation using lidocaine 2% gel seems to be a safe and effective treatment option for vulvodynia in women. (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Co, D. M., et al. (2022). Study of Envafolimab Alone or With Lenvatinib in Patients With Advanced Endometrial Cancer.
	No Results Available Drug: Envafolimab+Lenvatinib|Drug: Envafolimab ORR of Envafolimab alone or with Lenvatinib|The duration of response (DoR）|Disease control rate (DCR)|Time to response (TTR)|Progression-free survival (PFS)|To evaluate the overall survival (OS) in in subjects with advance endometrial cancer Female Phase 2 108 Industry Allocation: Non-Randomized|Intervention Model: Factorial Assignment|Masking: None (Open Label)|Primary Purpose: Treatment KN035-CN-011 October 2024

Coada Camelia, A., et al. (2023). "Optimal number of neoadjuvant chemotherapy cycles prior to interval debulking surgery in advanced epithelial ovarian cancer: a systematic review and meta-analysis of progression-free survival and overall survival." Journal of Gynecologic Oncology 34(6): e82.
	Objective: Neoadjuvant chemotherapy (NACT) represents a treatment option in patients with advanced epithelial ovarian cancer (AEOC) who are not good candidates for primary debulking surgery. Usually, 3 cycles of chemotherapy before surgery have been considered the best option for patient survival, although quite often some patients receive more than 3 cycles. The aim of this systematic review and meta-analysis was to identify the optimal number of NACT cycles reporting better survival in AEOC patients.; Methods: PubMed, Cochrane Library, and Scopus were searched for original articles that analyzed the relationship between the number of chemotherapy cycles and clinical outcomes in AEOC patients before interval debulking surgery (IDS). The main outcomes were progression-free survival (PFS) and overall survival (OS).; Results: A total of 22 studies comprising 7,005 patients diagnosed with AEOC were included in our analysis. In terms of survival, the reviewed studies dividing the patients in ≤3 NACT cycles vs. >3, showed a trend for a decrease in PFS and a significant reduction in OS with an increasing number of cycles, while a difference in both PFS and OS was revealed if early IDS included patients with 4 NACT cycles. These results should be interpreted with caution due to the complex characteristics of AEOC patients.; Conclusion: In conclusion, our review and meta-analysis revealed that there is not enough evidence to determine the optimal number of NACT treatments before surgery. Further research in the form of well-designed randomized controlled trials is necessary to address this issue.; Trial Registration: PROSPERO Identifier: CRD42022334959.; Competing Interests: No potential conflict of interest relevant to this article was reported. (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Coccolini, F., et al. (2021). "Intraperitoneal chemotherapy for ovarian cancer with peritoneal metastases, systematic review of the literature and focused personal experience." Journal of gastrointestinal oncology 12(Suppl 1): S144-S181.
	Epithelial ovarian cancer (EOC) causes 60% of ovarian cancer cases and is the fourth most common cause of death from cancer in women. The standard of care for EOC includes a combination of surgery followed by intravenous chemotherapy. Intraperitoneal (IP) chemotherapy (CT) has been introduced into the therapeutic algorithm of EOC with positive results. To explore existing results regarding intraperitoneal chemotherapy a systematic review of the literature and an analysis of our own institutional prospective database of patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) for EOC at different stages were conducted. The focused report concerning our personal experience with advanced EOC treated with cytoreductive surgery and HIPEC produced the following results: In 57 patients cisplatin + paclitaxel as HIPEC was the only significant factor improving overall survival (OS) at multivariate analysis (OR 6.54, 95% CI: 1.24-34.47, P=0.027). Patients treated with HIPEC cisplatin + paclitaxel showed a median OS of 46 months (SD 6.4, 95% CI: 33.4-58.6), while patients treated with other HIPEC regimens showed a median OS of 12 months (SD 3.1, 95% CI: 6.0-18.0). The 2y-OS was 72% and 3y-OS was 68% for cisplatin + paclitaxel as HIPEC, while the 2y- and 3y-OS was 0% for other HIPEC regimens. Patients treated with HIPEC cisplatin + paclitaxel showed a median disease-free survival (DFS) of 13 months (SD 1.6, 95% CI: 9.9-16.1), while patients treated with other HIPEC regimens showed a median DFS of 8 months (SD 3.1, 95% CI: 1.9-14.1). In conclusion, HIPEC cisplatin + paclitaxel in ovarian cancer showed positive results that may be considered semi-definitive according to the level of evidence and should be considered a starting point for further investigations. At present HIPEC cisplatin + paclitaxel should be proposed to patients with advanced ovarian cancer as standard treatment at almost all stages of disease. Platinum + taxane-based intraperitoneal regimens demonstrated superior results compared to other regimens.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-2020-06). The focused issue was sponsored by the Peritoneal Surface Oncology Group International (PSOGI). The authors have no other conflicts of interest to declare. (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Cochrane Kelsey, M., et al. (2023). "Optimizing vitamin D status in polycystic ovary syndrome: a systematic review and dose-response meta-analysis." Nutrition reviews.
	Context: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in women of reproductive age. Vitamin D supplementation is a promising complementary therapy for PCOS, yet there is no consensus on an optimal dose, leading to a lack of evidence-based supplementation guidelines.; Objective: The objective of this study was to conduct a vitamin D dose-response meta-analysis among women with PCOS.; Data Sources: MEDLINE, CINAHL, and EMBASE databases from inception to November 2022 were searched for relevant articles.; Data Extraction: Study screening and bias assessment were conducted by 2 independent reviewers. Eight relevant studies were identified; data for serum 25(OH)D (nmol/L) at baseline and at 12 weeks in each intervention group (mean ± SD) and vitamin D dose were extracted.; Data Analysis: Estimates across studies were used to create a pooled curve, using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles of the distribution of doses, to estimate the mean difference in effect for serum 25(OH)D at each dose compared with 0 IU/day. Sensitivity analyses were conducted fixing knots at 4000 IU/day and 7000 IU/day, which were a priori identified as potentially important thresholds, and to assess model fit and estimate heterogeneity. The pooled analysis demonstrated strong evidence of a dose-response relationship (P < .001), suggesting an increasing effect with increasing dose. An initial increase in serum 25(OH)D was evident until doses of approximately 3000 IU/day; this was followed by a plateau in effect between approximately 3000 IU/day and 5000 IU/day. The effect of supplementation with >5000 IU/day was unclear, given the minimal data at higher doses. The curve produced robust results for moderate doses (3000 IU/day to 4000 IU/day), which were not sensitive to model specification.; Conclusion: Women with PCOS are responsive to vitamin D supplementation, but the benefit of providing doses of >3000 IU/day appears minimal. Further data is required to determine dose-response at doses of >5000 IU/day, and whether higher intakes provide a clinically meaningful advantage in this population.; Systematic Review Registration: PROSPERO registration no. CRD42021259396. (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coelho, N., et al. (2020). "Definitions, prevalence, clinical implications and treatment of T-shaped uterus: systematic review." Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.
	OBJECTIVE: This study aims to summarize the current evidence regarding definitions, diagnosis, prevalence, clinical implications and impact of surgical treatment for T-shaped uterus not related to Diethystilbestrol (DES) exposure in a systematic review and to highlight what needs to be better clarified regarding T-shaped uterus. METHODS: A search on PubMed, Scopus and EMBASE was performed on Mar-2020. The following search terms were used: t-shaped OR t-shape OR infantile OR (lateral indentation) OR (Diethylstilbestrol OR DES) AND (uterus OR uterine OR uteri), AND (anomaly OR anomalies OR malformation OR malformations). Additionally, we hand-searched reference list from included studies for other relevant publications. All studies presenting any data regarding T-shaped uterus not related to DES exposure including at least 10 women were considered eligible. All the studies regarding DES-related T-shaped uterus were excluded because DES is not used since 1971. RESULTS: The search has found 2,504 records and 20 studies were included in the systematic review. There are only poor-quality studies (observational and quasi-experimental with uncontrolled before-after design). In most of the studies, the diagnosis of T-shaped uterus was based in three-dimensional US (3D-US) (11/16 studies). There is no consensus on definition of T-shaped uterus, but the most cited criteria (4/16 studies) is the criteria from European Society of Human Reproduction and Embryology and the European Society for Gynecological Endoscopy (ESHRE/ESGE) 2013 (narrow uterine cavity due to thickened lateral walls with a correlation 2/3 uterine corpus and 1/3 cervix), which is subjective. The prevalence of T-shaped uterus varied from 0.2-10% in the included studies. Regarding etiology of T-shaped uterus except for DES, there was mention to adenomyosis (1 study); adhesions (5 studies) and it was cited as primary condition (3 studies). Worse reproductive outcomes were related to T-shaped uterus due to infertility (9 studies), miscarriage (7 studies), preterm delivery (2 studies), ectopic pregnancy (1 study) and repeated implantation failure (7 studies). From the studies that analyzed benefits of surgical treatment by hysteroscopic metroplasty (12 studies), some of them had mentioned some improvement on pregnancy rate (49.6%- 88%; 8 studies), live birth rate (66.7-86.6%; 7 studies), term delivery rate (4 studies), reduction in miscarriage (12-24.2%; 5 studies) and ectopic pregnancy (1 study). This evidence is of very low quality with serious/critical risk of bias toward to overestimate the effect of the intervention, because it remains unknown whether before/after changes are the effect of metroplasty or other factors. Some authors reported no complications related to the procedure while others mentioned persistence of the dysmorphism (1.4-11%); bleeding (1.3%); infection (2.6%) and adhesions (11.1-16.8%). CONCLUSIONS: Until now, diagnosis, prevalence, and clinical relevance on reproductive outcomes in women with T-shaped uterus is unknown. Expectant management must be considered the most appropriate choice for daily practice until randomized controlled trials shows otherwise. This article is protected by copyright. All rights reserved.

Coelingh, B., et al. (2024). "Health benefits of combined oral contraceptives - a narrative review." The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception: 1-13.
	PURPOSE: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. METHOD(S): We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. RESULT(S): We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. CONCLUSION(S): The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription.

Coffman Lan, G., et al. (2022). "Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer." JCI insight 7(18).
	BACKGROUNDNew therapeutic combinations to improve outcomes of patients with ovarian cancer are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.METHODSThis phase I trial combined weekly carboplatin and paclitaxel chemotherapy with ribociclib, followed by ribociclib maintenance in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives were safety and maximum tolerated dose (MTD) of ribociclib when given with platinum and taxane chemotherapy. Secondary endpoints were response rate (RR) and progression-free survival (PFS).RESULTSThirty-five patients were enrolled. Patients had a mean of 2.5 prior lines of chemotherapy, and 51% received prior maintenance therapy with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab. The MTD was 400 mg. The most common adverse events included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), and nausea (77.1%). The overall RR was 79.3%, with a stable disease rate of 18%, resulting in a clinical benefit rate of 96.6%. Median PFS was 11.4 months. RR and PFS did not differ based on the number of lines of prior chemotherapy or prior maintenance therapy.CONCLUSIONThis work demonstrates that the combination of ribociclib with chemotherapy in ovarian cancer is feasible and safe. With a clinical benefit rate of 97%, this work provides encouraging evidence of clinical efficacy in patients with recurrent platinum-sensitive disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03056833.FUNDINGThis investigator-initiated trial was supported by Novartis, which provided drugs and funds for trial execution.

Cohen, C. R. (2021). "The promise of Lactobacillus crispatus CTV-05 (LACTIN-V) to prevent recurrence of bacterial vaginosis, HIV acquisition, and pretermlabor." American Journal of Reproductive Immunology 85(SUPPL 1): 34‐35.
	Problem: Bacterial vaginosis (BV) affects 15‐50% of women worldwide. After treatment with antibiotics, 20‐75% of women have recurrent BV within 3 months. BV has been associated with an increased risk of HIV and premature birth. Method of Study: We conducted a randomized, placebo‐controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV‐05 (LACTIN‐V) to prevent the recurrence of BV following antibiotic treatment. Women 18‐45 years of age who diagnosed with BV and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered LACTIN‐V or placebo for 11 weeks; follow‐up occurred through week 24. To address the effect of metronidazole treatment failure on the efficacy of LACTIN‐V on BV recurrence, we performed post hoc analyses to determine: 1) the effect of LACTIN‐V on therapeutic test of cure (TOC) at the 4‐week visit, and BV recurrence rates for LACTIN‐V vs. placebo in the TOC cohort analysis at the 12‐and 24‐week visits. Genital cytokine levels were assayed for 48 participants who reported near‐perfect adherence to assigned treatment during the trial. Vaginal swabs were collected before and after metronidazole therapy, and then at 4‐, 8‐, 12‐, and 24‐weeks. The primary comparison was the impact of LACTIN‐V use on vaginal levels of IL‐1α, the prototypic inflammatory cytokine elevated during BV. Results: A total of 228 women underwent randomization: 152 to the LACTIN‐V group and 76 to the placebo group; of these participants, In the intention‐to‐treat population, recurrence of BV by week 12 occurred in 46 participants (30%) in the LACTIN‐V group and in 34 participants (45%) in the placebo group (RR = 0.66; 95%CI, 0.44‐0.87; p = .01). The risk ratio for recurrence by week 24 was 0.73 (95%CI, 0.54‐0.92). At the 12‐week visit, L crispatus CTV‐05 was detected in 79% of participants in the LACTIN‐V group. Following treatment with metronidazole, 72 (47.7%) participants in the LACTIN‐V group met the therapeutic TOC criteria 4‐weeks after treatment compared to 25 (32.9%) participants in the placebo group (RR = 0.77; 95% CI 0.59‐1.00; p = .05). Furthermore, by restricting the analysis to the TOC cohort, recurrence of BV by week 24 occurred in 14 of 72 (19.4%) in the LACTIN‐V arm compared to 9 of 25 (36%) in the placebo arm (RR = 0.49, 95%CI 0.25‐0.95). Among the 48 participant in the immune study, vaginal IL‐1α levels fell promptly in all participants immediately following metronidazole treatment (3.319 vs. 2.832; p = .0055). While this reduction was sustained for at least 24 weeks among participants subsequently receiving LACTIN‐V, vaginal IL‐1α levels rebounded to baseline levels by 24 weeks in the placebo arm (p = .012). Conclusions: Treatment with LACTIN‐V following standard antibiotic treatment of BV not only reduced BV recurrence and increased L crispatus CTV‐05 colonization, but also resulted in more sustained reductions in vaginal IL‐1α levels. Given the link between genital pro‐inflammatory cytokines with female HIV acquisition and preterm delivery, LACTIN‐V may represent a novel strategy to reduce the risk of both conditions.

Cohen, D., et al. (2023). "A lesson in humility: the added values of PET-MRI over PET-CT in detecting malignant hepatic lesions." European Journal of Nuclear Medicine and Molecular Imaging 50(5): 1423-1433.
	Purpose: The recent introduction of integrated PET-MRI systems into practice seems promising in oncologic imaging, and efforts are made to specify their added values. The current study evaluates the added values of PET-MRI over PET-CT in detecting active malignant hepatic lesions. Method(s): As part of an ongoing prospective study in our institution that assesses the added values of PET-MRI, subjects undergo PET-CT and subsequent PET-MRI after single radiotracer injection. The current study included 97 pairs of whole-body PET-CT and liver PET-MRI scans, of 61 patients (19/61 had >= 2 paired scans), all performed with [18F]FDG and interpreted as showing active malignant hepatic involvement. Primary malignancies were of colorectal/biliary/pancreatic/breast/other origins in 19/9/9/7/17 patients. Monitoring response to therapy was the indication in 86/97 cases. When PET-MRI detected additional malignant lesions over PET-CT, lesions size, their characteristics on PET-MRI, and the influence on the final report were recorded. Result(s): In 37/97 (38.1%) cases, a total of 78 malignant lesions were identified on PET-MRI but not on PET-CT: 19 lesions (11 cases) were identified on PET of PET-MRI but not on PET of PET-CT; 37 lesions (14 cases) were small (<= 0.8 cm) and identified on MRI only; 22 lesions (12 cases) were > 0.8 cm, had low/no [18F]FDG uptake, but were categorized as viable based on MRI. These 78 lesions caused major effect on final reports in 11/97 (11.3%) cases, changing reported response assessment category (10/86 cases) or defining malignant hepatic disease on staging/restaging scans (1/11 cases). Conclusion(s): PET-MRI offers several advantages over PET-CT in assessing the extent and response to therapy of malignant hepatic involvement. Additional malignant lesions detected on PET-MRI are attributed to superior PET performance (compared with PET of PET-CT), greater spatial resolution provided by MRI, and improved multi-parametric viability assessment. In around one-tenth of cases, findings identified on PET-MRI but not on PET-CT significantly change the final report's conclusion.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Cohen Paul, A., et al. (2019). "Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data." Gynecologic Oncology 154(2): 441-448.
	Objective: There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.; Methods: We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).; Results: 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P < 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027).; Conclusions: CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Coitinho, B., et al. (2023). "Hypnotherapy for chronic pelvic pain: A scoping systematic review and meta-analysis." Complementary Therapies in Clinical Practice 52: 101771.
	Background: Chronic pelvic pain (CPP) is typically managed with anti-inflammatory analgesics and opioids; however, these do not adequately manage the pain or address the associated negative impact on quality of life. Hypnotherapy has been found to reduce pain associated with a range of disorders, including some with symptoms of chronic pain.; Aim: The aim of this review is to systematically scope research investigating the use of hypnosis on chronic pelvic pain, quality of life, anxiety, depression and fatigue.; Method: The scoping review was guided by the method described by Arksey and O'Mallee [1]. A systematic search was conducted in six databases. The Covidence Risk of Bias tool and the National Institutes of Health (NIH) quality assessment tool were used.; Results: Nine studies (four RCT's and five case series) were suitable for inclusion. Meta-analysis of the RCT's found no significant difference in pain or quality of life for the intervention group compared to controls. Only one study reported a reduction in pain after hypnotherapy and did not outperform controls. These results are limited due to lack of a standardised intervention and heterogeneity of the included studies.; Conclusion: There is a need for further research using well designed randomized controlled trials with validated measures of pain, quality of life, anxiety, depression and fatigue. Hypnotherapy interventions utilised in further research should be grounded in evidence-based best practice for dealing with pain.; Competing Interests: Declaration of competing interest None. (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cokan, A., et al. (2021). "Comparison of conservative treatment of cervical intraepithelial lesions with imiquimod with standard excisional technique using lletz: a randomized controlled trial." Journal of Clinical Medicine 10(24).
	(1) Background: There are limited data on the success of conservative treatment of high‐grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. (2) Methods: Patients aged 18–40 with histological HSIL (with high‐grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (p < 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%, p = 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (p‐value < 0.001) and 51.9% vs. 13.5% (p‐value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.

Cole, J., et al. (2019). "A systematic review of the safety and effectiveness of repetitive transcranial magnetic stimulation in the treatment of peripartum depression." Journal of Psychiatric Research 115: 142-150.
	Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is an efficacious treatment for major depressive disorder (MDD), however there is limited safety and efficacy data in the peripartum period. The purpose of this review is to systematically examine the safety, acceptability and effectiveness of rTMS administered during the peripartum period as an intervention for MDD. Method(s): We searched MEDLINE, EMBASE and PsychINFO from 2008 to January 2019 to identify peer reviewed publications evaluating rTMS during the peripartum period as an intervention for peripartum MDD. We systematically extracted reported adverse events, side effects, rates of discontinuation, as well as clinical response and remission. Result(s): Data was synthesized from 1 randomized control trial, 3 uncontrolled trials, 3 case series and 5 case studies, representing a total of 87 patients. No serious adverse events were reported. Side effects occurred at rates comparable to those observed in the non-peripartum population, and obstetric and neonatal complications are infrequent and do not separate from sham-rTMS. Randomized controlled data suggests antidepressant efficacy with an effect size of 0.87. Uncontrolled studies report rates of clinical response between 41.4% and 71.4%, and rates of clinical remission between 20.7 and 30.0%. The treatment appears acceptable, with few patients opting to discontinue treatment. Limitation(s): Due to the paucity of research in this population, majority of data comes from sources with inherently higher risk of bias. Conclusion(s): rTMS in the peripartum period appears to be efficacious, acceptable and well tolerated. Additional research is required, however rTMS's risk benefit profile may be attractive to women in the peripartum period.Copyright © 2019 Elsevier Ltd

Coleman, N., et al. (2024). "Phase I study of sapanisertib (CB-228/TAK-228/MLN0128) in combination with ziv-aflibercept in patients with advanced solid tumors." Cancer Medicine 13(3): e6877.
	Background: Sapanisertib is a potent ATP-competitive, dual inhibitor of mTORC1/2. Ziv-aflibercept is a recombinant fusion protein comprising human VEGF receptor extracellular domains fused to human immunoglobulin G1. HIF-1α inhibition in combination with anti-angiogenic therapy is a promising anti-tumor strategy. This Phase 1 dose-escalation/expansion study assessed safety/ tolerability of sapanisertib in combination with ziv-aflibercept in advanced solid tumors.; Methods: Fifty-five patients with heavily pre-treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels.; Results: Fifty-five patients were enrolled and treated across a range of dose levels. Forty were female (73%), median age was 62 (range: 21-79), and ECOG PS was 0 (9, 16%) or 1 (46, 84%). Most common tumor types included ovarian (8), colorectal (8), sarcoma (8), breast (3), cervical (4), and endometrial (4). Median number of prior lines of therapy was 4 (range 2-11). Sapanisertib 4 mg orally 3 days on and 4 days off plus 3 mg/kg ziv-aflibercept IV every 2 weeks on a 28-day cycle was defined as the maximum tolerated dose. Most frequent treatment-related grade ≥2 adverse events included hypertension, fatigue, anorexia, hypertriglyceridemia, diarrhea, nausea, mucositis, and serum lipase increase. There were no grade 5 events. In patients with evaluable disease (n = 50), 37 patients (74%) achieved stable disease (SD) as best response, two patients (4%) achieved a confirmed partial response (PR); disease control rate (DCR) (CR + SD + PR) was 78%.; Conclusion: The combination of sapanisertib and ziv-aflibercept was generally tolerable and demonstrated anti-tumor activity in heavily pre-treated patients with advanced malignancies. (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Coleman, R. L., et al. (2021). "Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study." The Lancet. Oncology 22(5): 609‐619.
	BACKGROUND: Few effective second‐line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor‐directed antibody‐drug conjugate, in this patient population. METHODS: This multicentre, open‐label, single‐arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396. FINDINGS: 102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow‐up at the time of analysis was 10·0 months (IQR 6·1‐13·0). The confirmed objective response rate was 24% (95% CI 16‐33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment‐related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment‐related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment‐related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes. INTERPRETATION: Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer. FUNDING: Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups.

Coleman, R. L., et al. (2021). "Clinical and molecular characteristics of ariel3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian cancer (HGOC)." International Journal of Gynecological Cancer 31(SUPPL 4): A10.
	Objectives ARIEL3 is a placebo‐controlled randomized trial of the PARP inhibitor (PARPi) rucaparib as maintenance treatment in HGOC patients who responded to the latest line of platinum therapy (NCT01968213). Rucaparib improved progression‐ free survival (PFS) across all predefined subgroups. Here, we present an exploratory analysis of characteristics associated with exceptional benefit from rucaparib. Methods Patients were randomized 2:1 to rucaparib 600 mg BID or placebo. As of 31 Dec 2019 (data cutoff), 33/375 (9%) and 1/189 (0.5%) patients were still ongoing and receiving rucaparib or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were compared between patients who derived exceptional benefit (PFS ≥2 yrs), and those with disease progression on first scan (?12 wks; the short‐term subgroup) within each treatment arm. Results of 564 patients, 79/375 (21%) in the rucaparib arm and 4/189 (2%) in the placebo arm showed exceptional benefit. Within the rucaparib arm, exceptional benefit patients had more favorable clinical prognostic factors at baseline versus the short‐term subgroup (Table). Although BRCA mutations were enriched in the rucaparib exceptional benefit subgroup, 33/79 (42%) of these patients were BRCA wild type. Patterns of enrichment varied among other biomarkers. Overall trends were similar in the placebo arm. Conclusions Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics and known mechanisms of PARPi sensitivity. Our results suggest rucaparib can deliver exceptional benefit to a diverse set of patients with HGOC.

Collée, G. E., et al. (2020). "Interventions that Facilitate Shared Decision-Making in Cancers with Active Surveillance as Treatment Option: a Systematic Review of Literature." Current oncology reports 22(10): 101.
	Purpose of Review: Medical decisions concerning active surveillance are complex, especially when evidence on superiority of one of the treatments is lacking. Decision aids have been developed to facilitate shared decision-making on whether to pursue an active surveillance strategy. However, it is unclear how these decision aids are designed and which outcomes are considered relevant. The purpose of this study is to systematically review all decision aids in the field of oncological active surveillance strategies and outcomes used by authors to assess their efficacy.; Recent Findings: A search was performed in Embase, Medline, Web of Science, Cochrane, PsycINFO Ovid and Google Scholar until June 2019. Eligible studies concerned interventions aiming to facilitate shared decision-making for patients confronted with several treatment alternatives, with active surveillance being one of the treatment alternatives. Twenty-three eligible articles were included. Twenty-one articles included patients with prostate cancer, one with thyroid cancer and one with ovarian cancer. Interventions mostly consisted of an interactive web-based decision aid format. After categorization of outcomes, seven main groups were identified: knowledge, involvement in decision-making, decisional conflict, treatment preference, decision regret, anxiety and health-related outcomes. Although active surveillance has been implemented for several malignancies, interventions that facilitate shared decision-making between active surveillance and other equally effective treatment alternatives are scarce. Future research should focus on developing interventions for malignancies like rectal cancer and oesophageal cancer as well. The efficacy of interventions is mostly assessed using short-term outcomes.

Collineau, B., et al. (2023). "[Uterine leiomyosarcoma - French guidelines from the GSF/NETSARC and TMRG groups]." Bulletin du cancer 110(4): 440-449.
	Uterine leiomyosarcomas represent the most common uterine sarcomas. The prognosis is poor with metastatic recurrence in more than half of the cases. The purpose of this review is to make French recommendations for the management of uterine leiomyosarcomas within the framework of the French Sarcoma Group - Bone Tumor Study Group (GSF-GETO)/NETSARC+ and Malignant Rare Gynecological Tumors (TMRG) networks in order to optimize their therapeutic management. The initial assessment includes a MRI with diffusion perfusion sequence. The diagnosis is histological with a review in an expert center (Reference Network in Sarcoma Pathology (RRePS)). Total hysterectomy with bilateral salpingectomy, en bloc without morcellation, is performed when complete resection is possible, whatever the stage. There is no indication of systematic lymph node dissection. Bilateral oophorectomy is indicated in peri-menopausal or menopausal women. Adjuvant external radiotherapy is not a standard. Adjuvant chemotherapy is not a standard. It can be an option and consists in doxorobucin based protocols. In the event of local recurrence, the therapeutic options are based on revision surgery and/or radiotherapy. Systemic treatment with chemotherapy is most often indicated. In case of metastatic disease, surgical treatment remains indicated when resecable. In cases of oligo-metastatic disease, focal treatment of metastases should be considered. In the case of stage IV, chemotherapy is indicated, and is based on first-line doxorubicin-based protocols. In the event of excessive deterioration in general condition, management by exclusive supportive care is recommended. External palliative radiotherapy can be proposed for symptomatic purposes. (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Collins, L. C., et al. (2024). "Luteal Phase Defects and Progesterone Supplementation." Obstetrical and Gynecological Survey 79(2): 122-128.
	Importance Luteal phase defects (LPDs), or an insufficiency of progesterone production during the luteal phase of the menstrual cycle, have been identified as a potential cause of recurrent pregnancy loss (RPL), but its exact contribution to RPL is not well-defined. In addition, the role of exogenous progesterone supplementation during pregnancy remains controversial. Objective The goal of this review is to provide an updated, evidence-based summary of LPD, including prevalence and potential pathophysiologic mechanisms, and to explore the current controversies regarding progesterone supplementation for management and treatment of RPL. Evidence Acquisition A literature review identified relevant research using a PubMed search, Cochrane summaries, review articles, textbook chapters, databases, and society guidelines. Results Endogenous progesterone plays a crucial role in the first trimester of pregnancy, and therefore, insufficiency may contribute to RPL. However, the precise relationship between LPD and RPL remains unclear. Luteal phase defect is primarily a clinical diagnosis based on a luteal phase less than 10 days. Although there may be a possibility of incorporating a combined clinical and biochemical approach in defining LPD, the current lack of validated diagnostic criteria creates a challenge for its routine incorporation in the workup of infertility. Moreover, no treatment modality has demonstrated efficacy in improving fertility outcomes for LPD patients, including progesterone supplementation, whose inconsistent data do not sufficiently support its routine use, despite its minimal risk. It is imperative that women diagnosed with LPD should be worked up for other potential conditions that may contribute to a shortened luteal phase. Future work needs to focus on identifying a reproducible diagnostic test for LPD to guide treatment. Conclusions and Relevance Currently, the perceived relationship between LPD and RPL is challenged by conflicting data. Therefore, patients with an abnormal luteal phase should undergo a thorough workup to address any other potential etiologies. Although supplemental progesterone is commonly utilized for treatment of LPD and RPL, inconsistent supporting data call for exogenous hormone therapy to be only used in a research setting or after a thorough discussion of its shortcomings. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this activity, the learner will be better able to explain the various definitions, diagnostic criteria, and potential pathophysiologic mechanisms of LPD; discuss the current controversies surrounding the role of LPD within RPL; and delineate the current studies and recommendations for treatment, specifically the use of progesterone supplementation.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Collins, M. H., et al. (2022). "Brief Mindfulness Video to Reduce Pelvic Exam- Related Anxiety and Pain." Obstetrics and Gynecology 139(SUPPL 1): 26S‐27S.
	INTRODUCTION: Purpose: Pelvic examinations frequently cause anxiety and discomfort for women, which may lead to avoidance of medical appointments. This study evaluated the efficacy of a brief mindful movement video in reducing pelvic exam anxiety and pain. METHODS: Women (n=90) scheduled for pelvic examination were recruited at an outpatient gynecology clinic and randomized to mindfulness intervention (5‐minute mindful movement video [n=44]) or control (educative materials [n=46]) groups. Upon arrival, women completed baseline measurements of anxiety and pain (visual analogue scale [VAS]). They then completed group specific activities and rated anxiety prior to pelvic exam. After exam, participants rated exam pain, post‐exam anxiety, and completed questionnaires assessing intervention acceptability. RESULTS: Fifty‐two percent of women who presented for pelvic examination reported clinically significant anxiety (i.e., VAS .34). Analysis of covariance controlling for baseline anxiety found clinically anxious individuals who received the intervention reported significantly lower anxiety before pelvic examination (P=<.001, partial η2=.232) and after (P=.006, partial η2=.165) compared to control. Analysis of covariance controlling for baseline pain found individuals who received the intervention rated pelvic examination as significantly less painful (P=< .01, partial η2=.075) compared to control. Intervention participants reported high interest, acceptability, and helpfulness of the mindful movement video. CONCLUSION: A 5‐minute mindful movement video viewed prior to pelvic examination significantly lowered anxiety for individuals with clinically significant anxiety and reduced perceived painfulness of pelvic examination. This study demonstrates the ability to integrate a brief mindfulness intervention into the flow of a medical clinic and reduce pelvic exam anxiety and pain.

Colomban, O., et al. (2023). "Benefit From Fractionated Dose-Dense Chemotherapy in Patients With Poor Prognostic Ovarian Cancer: ICON-8 Trial." JCO clinical cancer informatics 7: e2200188.
	Purpose: An international meta-analysis identified a group of patients with advanced epithelial ovarian cancer (EOC) with a very poor survival because of two unfavorable features: (1) a poor chemosensitivity defined by an unfavorable modeled CA-125 ELIMination rate constant K (KELIM) score <1.0 with the online calculator CA-125-Biomarker Kinetics, and (2) an incomplete debulking surgery. We assumed that patients belonging to this poor prognostic group would benefit from a fractionated densified chemotherapy regimen.; Methods: The data set of ICON-8 phase III trial (ClinicalTrials.gov identifier: NCT01654146), where patients with EOC were treated with the standard three-weekly, or the weekly dose-dense, carboplatin-paclitaxel regimens and debulking primary surgery (immediate primary surgery [IPS] or delayed primary [or interval] surgery [DPS]), was investigated. The association between treatment arm efficacy, standardized KELIM (scored as favorable ≥1.0, or unfavorable <1.0), and surgery completeness was assessed by univariate/multivariate analyses in IPS and DPS cohorts.; Results: Of 1,566 enrolled patients, KELIM was calculated with the online model in 1,334 with ≥3 CA-125 available values (85%). As previously reported, both KELIM and surgery completeness were complementary prognostic covariates, and could be combined into three prognostic groups with large OS differences: (1) good if favorable KELIM and complete surgery; (2) intermediate if either unfavorable KELIM or incomplete surgery; and (3) poor if unfavorable KELIM and incomplete surgery. Weekly dose-dense chemotherapy was associated with PFS/OS improvement in the poor prognostic group in both the IPS cohort (PFS: hazard ratio [HR], 0.50; 95% CI, 0.31 to 0.79; OS: HR, 0.58; 95% CI, 0.35 to 0.95) and the DPS cohort (PFS: HR, 0.53; 95% CI, 0.37 to 0.76; OS: HR, 0.57; 95% CI, 0.39 to 0.82).; Conclusion: Fractionated dose-dense chemotherapy might be beneficial for patients belonging to the poor prognostic group characterized by lower tumor chemosensitivity assessed with the online calculator CA-125-Biomarker Kinetics and incomplete debulking surgery. Further investigation in the future SALVOVAR trial is warranted.

Colomban, O., et al. (2019). "Early Modeled Longitudinal CA-125 Kinetics and Survival of Ovarian Cancer Patients: A GINECO AGO MRC CTU Study." Clinical cancer research : an official journal of the American Association for Cancer Research 25(17): 5342-5350.
	Purpose: Regarding cancer antigen 125 (CA-125) longitudinal kinetics during chemotherapy, the actual predictive value of the Gynecologic Cancer Intergroup (GCIG) CA-125 response criterion is questioned. The modeled CA-125 elimination rate constant KELIM exhibited higher prognostic value in patients with recurrent ovarian cancer enrolled in the CALYPSO trial. The objective was to validate the higher predictive and prognostic values of KELIM during first-line treatments.; Experimental Design: Data from three large phase III trials were analyzed: AGO OVAR 9 [learning set: carboplatin-paclitaxel (CP) ± gemcitabine; n = 1,288]; AGO OVAR 7 (validation set: CP ± topotecan; n = 192); and ICON7 (validation set: CP ± bevacizumab; n = 1,388). The CA-125 profiles were fit with a nonlinear mixed-effect model during the first 100 days, and the individual KELIM were calculated. KELIM prognostic and predictive values for survival were assessed against GCIG criterion and other prognostic factors in univariate/multivariate analyses.; Results: The GCIG CA-125 endpoint provided no meaningful predictive/prognostic information. C-index analyses confirmed the higher predictive value of KELIM compared with GCIG criterion for progression-free survival and overall survival (OS). KELIM provided reproducible prognostic information. Patients with favorable KELIM ≥ upper tercile (0.0711 per days) consistently experienced better OS, with HRs between 0.44 and 0.58 (e.g., median OS >65 months vs. <35 months).; Conclusions: Modeled KELIM provides higher predictive and prognostic information based on CA-125 longitudinal kinetics compared with GCIG response criteria during first-line chemotherapy. Integration of this endpoint in guidelines may be considered. Individual KELIM and survival simulations can be calculated at http://www.biomarker-kinetics.org/. Further assessment of the surrogate value of KELIM treatment-related variations in a GCIG meta-analysis is warranted. See related commentary by Maitland et al., p. 5182 . (©2019 American Association for Cancer Research.)

Colombo, C., et al. (2023). "Does luteal phase progesterone supplementation affect physical and psychosocial well-being among women undergoing modified natural cycle-FET? A sub-study of a randomized controlled trial." Human reproduction (Oxford, England) 38(10): 1970-1980.
	Study Question: Are there any differences in physical and psychosocial well-being among women undergoing modified natural cycle frozen embryo transfer (mNC-FET) with or without vaginal progesterone as luteal phase support (LPS)?; Summary Answer: Women undergoing mNC-FET with vaginal progesterone supplementation were more likely to experience physical discomfort but there was no difference in psychosocial well-being between the two groups.; What Is Known Already: mNC-FET can be carried out with or without vaginal progesterone as LPS, which has several side-effects. It is commonly known that fertility treatment can cause stress and psychosocial strain, however, most studies on this subject are conducted in fresh cycle regimes, which differ from NC-FET and results may not be comparable.; Study Design, Size, Duration: This is a sub-study of an ongoing RCT investigating whether progesterone supplementation has a positive effect on live birth rate in mNC-FET. The RCT is conducted at eight fertility clinics in Denmark from 2019 and is planned to end primo 2024. The sub-study is based on two questionnaires on physical and psychosocial well-being added to the RCT in August 2019. On the time of data extraction 286 women had answered both questionnaires.; Participants/materials, Setting, Methods: Women who had answered both questionnaires were included in the sub-study. Participants were equally distributed, with 143 in each of the two groups. Participants in both groups received the same questionnaires at two time-points: on cycle day 2-5 (baseline) and after blastocyst transfer. Participants in the progesterone group had administered progesterone for 7 days upon answering the second questionnaire. All items in the questionnaires were validated. Items on psychosocial well-being originate from the Copenhagen Multi-Centre Psychosocial Infertility-Fertility Problem Stress Scale (COMPI-FPSS) and from the Mental Health Inventory-5.; Main Results and the Role of Chance: Women receiving progesterone experienced more vaginal itching and/or burning than women in the non-progesterone group (P < 0.001). Women in the progesterone group also experienced more self-reported vaginal yeast infection, this was, however, not significant after adjustment for multiple testing (P/adjusted P = 0.049/0.881). No differences regarding psychosocial well-being were found between the two groups. Within the progesterone group, a shift toward feeling less 'downhearted and blue' was found when comparing response distribution at baseline and after blastocyst transfer (P < 0.001).; Limitations, Reasons for Caution: All items on physical symptoms were self-reported. The item on vaginal yeast infection was therefore not diagnosed by a doctor. Inclusion in the study required a few extra visits to the clinic, participants who felt more burdened by fertility treatment might have been more likely to decline participation. Women who experienced a lot of side-effects to progesterone prior to this FET cycle, might be less likely to participate.; Wider Implications of the Findings: Our results are in line with previous known side-effects to progesterone. Physical side-effects of progesterone should be considered before administration.; Study Funding/competing Interest(s): The RCT is fully supported by Rigshospitalet's Research Foundation and a grant from Gedeon Richter. Gedeon Richter were not involved in the design of protocol nor in the conduction of the study or analysis of results. A.P., L.P., and N.I.-C.F. report grants from Gedeon Richter, Ferring and Merck with no relations to this study. N.I.-C.F. has received travel support from Ferring, Merck A/S, & Gideon Richter, and is the head of the steering committee for the Danish Fertility Guidelines made by the members of from the Danish Fertility Society. A.P. reports consulting fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, & Merck A/S, honoraria from Gedeon Richter, Ferring, Merck A/S, Theramex, and Organon, has received travel support from Gedeon Richter (payment to institution), pa ticipated on an advisory board for Preglem and was loaned an embryoscope from Gedeon Richter to their institution. A.L.S. has stock options for Novo Nordisk B A/S. B.A. have received unrestricted grant from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA, and Marckyrl Pharma.; Trial Registration Number: The RCT is registered on ClinicalTrials. gov (NCT03795220) and in EudraCT (2018-002207-34). (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Colombo, N., et al. (2024). "Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab." Oncologist 29(1): 25-35.
	Background: Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Material(s) and Method(s): In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Result(s): As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence >=10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion(s): Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. Clinicaltrials.gov ID: NCT03517449Copyright © 2024 Wiley-Blackwell. All rights reserved.

Colombo, N., et al. (2021). "Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial." Gynecologic Oncology 163(1): 41-49.
	OBJECTIVES: In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1. METHODS: Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260) or placebo (N = 131), with a 2-year treatment cap in most patients. Safety outcomes were analyzed in detail in randomized patients who received at least one dose of study drug (olaparib, n = 260; placebo, n = 130). RESULTS: Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was <3 months in olaparib-treated patients. The first event of anemia, neutropenia, thrombocytopenia, nausea and vomiting lasted a median of <2 months and the first event of fatigue/asthenia lasted a median of 3.48 months in the olaparib group. These adverse events were manageable with supportive treatment and/or olaparib dose modification in most patients, with few patients requiring discontinuation of olaparib. Of 162 patients still receiving olaparib at month 24, 64.2% were receiving the recommended starting dose of olaparib 300 mg twice daily. CONCLUSIONS: Maintenance olaparib had a predictable and manageable adverse event profile in the newly diagnosed setting with no new safety signals identified. Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients.

Colombo, N., et al. (2021). "Relacorilant, a selective glucocorticoid receptor modulator, in combination with nab-paclitaxel improves progression-free survival in patients with recurrent platinum-resistant ovarian cancer: a 3-arm, randomized, open-label, phase II study."  32: S725‐.
	Background: Pre‐clinical and clinical data indicate that glucocorticoid receptor (GR) antagonism may enhance/restore chemotherapy sensitivity. This is the first randomized, controlled study to explore the efficacy and safety of relacorilant (RELA), a selective GR modulator, in combination w/ nab‐paclitaxel (nab‐pac) compared to nab‐pac alone. Methods: Women w/ recurrent platinum‐resistant/refractory high grade serous or endometroid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma w/ measurable or non‐measurable disease and up to 4 chemotherapeutic regimens were 1:1:1 randomized to: ‐CONTINUOUS 100mg RELA daily (w/discretionary escalation to 150mg) + 80mg/m2 nab‐pac on days 1, 8, and 15 of a q28‐day schedule; or ‐INTERMITTENT 150mg RELA the day before, of, and after 80mg/m2 nab‐pac on days 1, 8, and 15, of a q28‐day schedule; or ‐COMPARATOR,100mg/m2 nab‐pac on days 1, 8, and 15, of a q28‐day schedule. A lower nab‐pac dose was used with RELA because RELA inhibits the metabolism of nab‐pac. The primary endpoint was progression‐free survival (PFS) determined by the investigator per RECIST 1.1. Results: 178 women were randomized. At median follow‐up of 11.07 mos, the INTERMITTENT regimen significantly improved median PFS compared to nab‐pac alone (HR, 0.66, 95%CI 0.44‐0.98, log‐rank test p=0.038). While ORR was similar, Duration of Response (DoR) was significantly improved (HR 0.36, 95% 0.16‐0.77, p=0.006) in the INTERMITTENT regimen vs. nab‐pac alone. Overall survival will be assessed at maturity. Most common grade ?3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy. [Formula presented] Conclusions: INTERMITTENT RELA + nab‐pac improved PFS and had a favorable safety profile in recurrent platinum‐resistant and/or platinum‐refractory ovarian cancer patients. Clinical trial identification: NCT03776812. Legal entity responsible for the study: Corcept Therapeutics. Funding: Corcept Therapeutics. Disclosure: N. Colombo: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker?s Bureau: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Speaker?s Bureau: Clovis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker?s Bureau: MSD; Financial Interests, Personal, Speaker?s Bureau: GSK; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Oncxe; Financial Interests, Personal, Speaker?s Bureau, Corcept Therapeutics: Novartis; Financial Interests, Personal, Principal Investigator: Corcept Therapeutics. D.D. Nguyen: Financial Interests, Personal, Full or part‐time Employment: Corcept Therapeutics. G.F. Fleming: Financial Interests, Personal, Principal Investigator: Corcept Therapeutics; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: Syros; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Principal Investigator: Iovance; Financial Interests, Personal, Principal Investigator: Sermonix; Financial Interests, Personal, Principal Investigator: Compugen; Financial Interests, Personal, Principal Investigator: Celldex; Financial Interests, Personal, Principal Investigator: Plexxicon; Financial Interests, Personal, Principal Investigator: AstraZeneca. R.N. Grisham: Financial Interests, Personal, Advisory Board: Signatera; Financial Interests, Personal, Advisory Board: Verastem; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: PER; Financial Interests, Pe sonal, Advisory Board: Aptitude; Financial Interests, Personal, Principal Investigator: Corcept Therapeutics; Financial Interests, Personal, Principal Investigator: Context; Financial Interests, Personal, Principal Investigator: Verastem; Financial Interests, Personal, Principal Investigator: Bayer; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Novartis. D. Lorusso: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker?s Bureau: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Other, Travel Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Speaker?s Bureau: Clovis; Financial Interests, Personal, Principal Investigator: Clovis; Financial Interests, Personal, Principal Investigator: Corcept Therapeutics; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Speaker?s Bureau: GSK; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Other, Travel Grant: GSK; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Advisory Board: Pharmamar; Financial Interests, Personal, Principal Investigator: Immonogen; Financial Interests, Personal, Principal Investigator: Genmab; Financial Interests, Personal, Other, Travel Grant: Roche. T. Van Gorp: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: OncXerna; Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: Corcept Therapeutics. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Institutional, Principal Investigator: Abbvie Deutschland; Financial Interests, Institutional, Principal Investigator: Ability; Financial Interests, Institutional, Principal Investigator: Advaxis; Financial Interests, Institutional, Principal Investigator: Aeterna Zentaris. H.I. Pashova: Financial Interests, Personal, Full or part‐time Employment: Corcept Therapeutics. A. Grauer: Financial Interests, Personal, Full or part‐time Employment: Corcept Therapeutics.

Colombo, N., et al. (2023). "Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(30): 4779-4789.
	Purpose: Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.; Methods: This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m 2 ) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m 2 ) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m 2 ). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points.; Results: A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 ( P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events.; Conclusion: Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance ( P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408).

Colonetti, L., et al. (2022). "Green tea promotes weight loss in women with polycystic ovary syndrome: Systematic review and meta-analysis." Nutrition research (New York, N.Y.) 104: 1-9.
	Among the main consequences of polycystic ovary syndrome (PCOS) are menstrual dysfunction, infertility, hyperandrogenism, insulin resistance, and weight gain; in aggravated cases, it can become a risk factor for the development of metabolic syndrome and cardiovascular disease. We hypothesized that green tea can be an option to complement the treatment of PCOS. Thus, this systematic review aims to evaluate the effects of green tea supplementation in women with PCOS. We searched for randomized controlled trials (RCTs) that evaluated women with PCOS who received green tea compared with placebo in electronic databases: MEDLINE via PubMed, EMBASE via Elsevier, Cochrane Library, LILACS via BVS, and Web of Science using the terms: "polycystic ovary syndrome," "green tea," "Camellia sinensis," "epigallocatechin gallate." The outcomes listed in the study protocol were body weight, fasting insulin, body mass index, body fat percentage, daily caloric intake, waist circumference, hip circumference, and waist/hip ratio. Four double-blind RCTs were included, with a total of 169 women: 85 in the green tea group and 84 in the placebo group. We found a significantly lower body weight (kg) for green tea group (mean difference, -2.80; 95% confidence interval, -5.25 to -0.35; P = .03; I² = 0%; 4 studies, 169 participants, very low-quality evidence). Green tea has potential positive effects for the reduction of weight, and future studies will be needed to confirm the estimated effect size; we reasonably expect this to be an option of adjuvant treatment in PCOS clinical management. Registration number: CRD42021226296. (Copyright © 2022. Published by Elsevier Inc.)

Columbia University of, B., et al. (2022). The SUPPORT Study: Effectiveness and Usability of a Web-Enabled Resource for Postpartum Mental Health.
	No Results Available Other: Postpartumcare.ca (Web-Enabled Intervention) Change from Baseline Postpartum Depression at 4 weeks and 6 weeks, evaluated using the Edinburgh Postnatal Depression Scale (EPDS).|Change from Baseline Postpartum Anxiety at 4 weeks and 6 weeks, evaluated using the Perinatal Anxiety Screening Scale (PASS).|Website usability, as evaluated using the System Usability Scale (SUS)|Website satisfaction, evaluated using the Patient Global Impression of Change (PGIC) questionnaire|Website satisfaction, evaluated using the user-perceived web quality instrument|Website satisfaction, evaluated using the Patient Education Materials Assessment Tool (PEMAT)|Website metrics including average time on page, average session duration, returning visitors, and number of pages visited per session. All Phase 2 103 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment H21-03407 May 1, 2023

Comba, C., et al. (2022). "The effect of omentectomy on the blood levels of adipokines in obese patients with endometrial cancer." Obesity Research & Clinical Practice 16(3): 242-248.
	Objective: To investigate the blood levels of adipokines in obese patients with endometrial cancer who have and have not undergone omentectomy.; Methods: Between September 2017 and September 2019, the study recruited 54 patients with endometrial cancer. Measurements were taken of blood levels of human leptin, perilipin-1, adiponectin, adipolin, resistin, visfatin, and estrone preoperatively and postoperatively before adjuvant therapy or at the end of one month. The serum samples were separated by centrifugation for 10 mins at 3,000 revolutions/min, then stored at -80 °C until assay.; Results: In this prospective study, a total of 54 endometrial cancer patients were analyzed in two separate groups according to the omentectomy status. Comprehensive staging surgery with omentectomy and without omentectomy was performed in 26 patients and 28 patients, respectively. The age, body mass index, body fat index, waist circumference, and skin thickness values of the patients with and without omentectomy were found to be similar. No statistically significant difference was determined between the patients with and without omentectomy in respect of the blood level of the adipokines measured preoperatively. A strong statistically significant correlation was determined between the pre and postoperative levels of Human Leptin (p = 0.002), perilipin-1(p = 0.001), adipolin (p < 0.001), adiponectin (p < 0.001), resistin (p = 0.001), visfatin (p < 0.001), and estrone (p = 0.004) (r = -0.43, -0.47, 0.75, 0.84, -0.47, - 0.58, -0.41, respectively) CONCLUSIONS: Omentectomy affected the postoperative blood levels of adipokines in obese patients with endometrial cancer. As omentectomy may have some positive effects on metabolism in these patients, it may be considered during endometrial cancer surgery due to the possible positive metabolic effects. (Copyright © 2022. Published by Elsevier Ltd.)

Combs, A., et al. (2023). "A Systematic Review of Vitamin D and Fibroids: Pathophysiology, Prevention, and Treatment." Reproductive sciences (Thousand Oaks, Calif.) 30(4): 1049-1064.
	Uterine fibroids are the most common tumor of reproductive-age women worldwide and cause significant morbidity in affected women. Vitamin D has emerged as a potential therapy for uterine fibroids based on experimental and epidemiologic evidence. The objective of this systematic review was to evaluate the role of vitamin D in the pathophysiology of uterine fibroids and its efficacy for prevention and treatment of fibroids. A comprehensive search was conducted of Cochrane Library, Embase, PubMed, Scopus, and Web of Science from inception to March 2022. English-language publications that evaluated vitamin D and uterine fibroids in humans, whether experimental or clinical, were considered. The search yielded 960 publications, and 89 publications met inclusion criteria: 23 preclinical studies, 25 clinical studies, and 41 review articles. Preclinical studies indicated that the vitamin D receptor was decreased in fibroid cells. Vitamin D treatment of fibroid cells decreased proliferation, extracellular matrix protein expression, and Wnt/β-catenin signaling. Fourteen clinical studies (n = 3535 participants) assessed serum vitamin D level in women with ultrasound-proven fibroids, and all found an inverse correlation between serum vitamin D level and presence of fibroids. Five clinical studies (n = 472 patients) evaluated treatment of fibroids with vitamin D. Four of five studies showed vitamin D significantly inhibited fibroid growth. One pilot study (n = 109 patients) of vitamin D for secondary prevention of fibroids demonstrated smaller recurrent fibroids in the treated group. These studies provide evidence for vitamin D as a therapy for uterine fibroids and underscore the need for well-designed, randomized, placebo-controlled clinical trials. (© 2022. Society for Reproductive Investigation.)

Combs, J. C., et al. (2022). "DO THE NUMBERS ADD UP FOR PERSONALIZED EMBRYO TRANSFER? – A COST EFFECTIVENESS ANALYSIS STUDY." Fertility and Sterility 118(5): e26.
	Background: As efforts to maximize assisted reproductive outcomes continue, focus has turned to endometrial receptivity analysis (ERA) as a possible next frontier. Current testing offers assessment of 238 genes via endometrial tissue biopsy during a mock transfer cycle and produces a computationally predicted window of implantation to guide the timing of future embryo transfers[1]. Conflicting data exists as to the clinical efficacy of ERA and minimal analysis has been done regarding the cost effectiveness of this additional testing. Objective: To evaluate the cost effectiveness of ERA derived personalized embryo transfer (PET) versus fresh (FT) and frozen embryo transfer (FET). Materials and Methods: A decision‐tree mathematical model comparing PET versus FT versus FET was created. Live birth rates were obtained from previously published randomized controlled trial data and costs from published literature [1‐3]. Average cost per live birth in each transfer modality was calculated for the initial transfer and one additional frozen embryo transfer. Sensitivity analyses were performed over a range of procedural costs and live birth rates. Results: Fresh embryo transfer had the lowest average cost per live birth following initial transfer at $43,368 versus $65,125 for PET and $68,726 for FET. PET would need a live birth rate of ≥61% compared to fresh transfer (44.1%) to be cost effective. Even if PET added >source in cost, it was never cost effective versus fresh embryo transfer. PET was cost effective versus planned FET when adding <$4100 in cost. Following a second transfer, the fresh‐then‐frozen modality again had the lowest average cost per live birth at $37,076 versus $46,601 for PET and $48,288 for FET. Through two embryo transfers, PET would need a cumulative live birth rate of 79% compared to fresh transfer (58.6%) to be cost effective. Even if PET added >source in cost, it was never cost effective versus fresh‐then‐frozen embryo transfer. PET was cost effective versus planned FET when adding <$3700 in cost. Conclusions: Our model suggests that ERA derived PET is less cost‐effective than traditional fresh‐then supernumerary‐frozen embryo transfer. Future evaluation of these findings is needed as ERA processing migrates to the Next Generation Sequencing platform and additional clinical efficacy data is published. Support: No disclosures REFERENCES: 1. Simon, C., et al., A 5‐year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod Biomed Online, 2020. 41(3): p. 402‐415. 2. Evans, M.B., et al., Evaluation of the cost‐effectiveness of ovulation suppression with progestins compared with GnRH analogs in assisted reproduction cycles. Reprod Biomed Online, 2019. 38(5): p. 691‐698. 3. Neal, S.A., et al., Preimplantation genetic testing for aneuploidy is cost‐effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage. Fertil Steril, 2018. 110(5): p. 896‐904.

Comini, A. C. M., et al. (2023). "Safety and Serum Estradiol Levels in Hormonal Treatments for Vulvovaginal Atrophy in Breast Cancer Survivors: A Systematic Review and Meta-Analysis." Clinical Breast Cancer 23(8): 835-846.
	Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.Copyright © 2023 Elsevier Inc.

Conceptra, B. and Llc (2023). CCT-102 vs. Expectant Management in Delayed Pregnancy Loss.
	No Results Available Combination Product: CCT-102 A and CCT-102 B Resolution of pregnancy loss Female Phase 3 160 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment PRT-CO-CCT-102.001 July 2024

Conforti, A., et al. (2021). "Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review." Frontiers in Reproductive Health 3: 634813.
	Luteal phase support (LPS) is crucial in assisted reproductive technology (ART) cycles when the luteal phase has been found to be defective. Such deficiency is most likely related to the supraphysiological steroid levels that usually occurr in stimulated cycles which, in turn, could severely affect luteinizing hormone (LH) secretion and function, thereby negatively influencing the luteal phase. A number of different medications and routes have been successfully used for LPS in ART. Although an optimal protocol has not yet been identified, the existing plethora of medications offer the opportunity to personalize LPS according to individual needs. Subcutaneous administration progesterone has been proposed for LPS and could represent an alternative to a vaginal and intramuscular route. The aim of the present systematic review is to summarize the evidence found in the literature concerning the application of subcutaneous progesterone in ARTs, highlighting the benefits and limits of this novel strategy. With this aim in mind, we carried out systematic research in the Medline, ISI Web of Knowledge, and Embase databases from their inception through to November 2020. Randomized controlled trials (RCTs) were preferred by the authors in the elaboration of this article, although case-control and cohort studies have also been considered. According to our findings, evidence exists which supports that, in women with a good prognosis undergoing a fresh in vitro fertilization (IVF) cycle, subcutaneous Pg is not inferior to vaginal products. In the Frozen-thawed embryo transfer (FET) cycle, data concerning efficacy is mixed with an increased miscarriage rate in women undergoing a subcutaneous route in oocyte donor recipients. Data concerning the acceptance of the subcutaneous route versus the vaginal route are encouraging despite the different scales and questionnaires which were used. In addition, a cost-effective analysis has not yet been conducted.; Competing Interests: AC and CA decleare fees from Merck Serono Italia outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Conforti, Carbone, Iorio, Cariati, Bagnulo, Marrone, Strina and Alviggi.)

Conforti, A., et al. (2019). "The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis." Reproductive biology and endocrinology : RB&E 17(1): 18.
	Objective: To study the role of recombinant human LH supplementation in women with hypo-response to ovarian stimulation.; Methods: We performed a systematic review and meta-analysis of prospective clinical trials in which recombinant FSH monotherapy protocols were compared with LH-supplemented protocols in hypo-responders. A search was conducted of the Scopus, MEDLINE databases without time or language restrictions. Primary outcome was clinical pregnancy rate.; Results: Significantly higher clinical pregnancy rates (odds ratio: 2.03, P = 0.003), implantation rates (odds ratio: 2.62, P = 0.004) and number of oocytes retrieved (weight mean differences: 1.98, P = 0.03) were observed in hypo-responders supplemented with recombinant LH versus hypo-responders who underwent FSH monotherapy. No differences in terms of mature oocytes or miscarriage rates were found between the two groups.; Conclusion: In conclusion, our analysis confirms that women with a hypo-response to exogenous gonadotropins might benefit from LH supplementation. However, more trials are required before a definitive conclusion can be drawn.

Conic Rosalynn, R. Z., et al. (2024). "Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data." BMC Urology 24(1): 21.
	Background: Urologic chronic pelvic pain syndrome (UCPPS), which includes interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis (CP/CPPS), is associated with increased voiding frequency, nocturia, and chronic pelvic pain. The cause of these diseases is unknown and likely involves many different mechanisms. Dysregulated renin-angiotensin-aldosterone-system (RAAS) signaling is a potential pathologic mechanism for IC/BPS and CP/CPPS. Many angiotensin receptor downstream signaling factors, including oxidative stress, fibrosis, mast cell recruitment, and increased inflammatory mediators, are present in the bladders of IC/BPS patients and prostates of CP/CPPS patients. Therefore, we aimed to test the hypothesis that UCPPS patients have dysregulated angiotensin signaling, resulting in increased hypertension compared to controls. Secondly, we evaluated symptom severity in patients with and without hypertension and antihypertensive medication use.; Methods: Data from UCPPS patients (n = 424), fibromyalgia or irritable bowel syndrome (positive controls, n = 200), and healthy controls (n = 415) were obtained from the NIDDK Multidisciplinary Approach to the Study of Chronic Pelvic Pain I (MAPP-I). Diagnosis of hypertension, current antihypertensive medications, pain severity, and urinary symptom severity were analyzed using chi-square test and t-test.; Results: The combination of diagnosis and antihypertensive medications use was highest in the UCPPS group (n = 74, 18%), followed by positive (n = 34, 17%) and healthy controls (n = 48, 12%, p = 0.04). There were no differences in symptom severity based on hypertension in UCPPS and CP/CPPS; however, IC/BPS had worse ICSI (p = 0.031), AUA-SI (p = 0.04), and BPI pain severity (0.02). Patients (n = 7) with a hypertension diagnosis not on antihypertensive medications reported the greatest severity of pain and urinary symptoms.; Conclusion: This pattern of findings suggests that there may be a relationship between hypertension and UCPPS. Treating hypertension among these patients may result in reduced pain and symptom severity. Further investigation on the relationship between hypertension, antihypertensive medication use, and UCPPS and the role of angiotensin signaling in UCPPS conditions is needed. (© 2024. The Author(s).)

Conklin, D. Y. and G. Karakurt (2023). "Women with mood disorders and couples conflict: menopause symptom improvement, after group therapy." Climacteric : the journal of the International Menopause Society 26(6): 565-570.
	Objective: Although a public health crisis, intimate partner violence (IPV) has been understudied for middle-aged women with mood disorders during their perimenopausal and postmenopausal years. The aims of this study were to examine the relationship between IPV and hot flashes/night sweats (HF/NS) frequency and severity among women with mood disorders and to test whether the effect of cognitive behavioral group therapy on menopausal symptoms differs between those with and without IPV at baseline and post-test.; Methods: Of 59 participants from a mood disorders outpatient clinic enrolled in the parent study, 24 experienced IPV. This study analyzed pretreatment and post-treatment data from the Revised Conflict Tactic Scale - Short Form-2, and HF/NS frequency and severity ratings on the Hot Flash Daily Diary using the McNemar chi-square test.; Results: The presence of any type of violence at pretreatment was significantly ( p < 0.01) linked to improvements in HF/NS frequency and severity. Women who showed improvements in negotiation skills had better outcomes in menopausal symptoms. Sexual coercion increased from one to three women.; Conclusions: Negotiation skills may help women with mood disorders to reduce HF/NS frequency and severity. More studies need to be conducted with a special focus on helping women in this population.

Conley Alexander, C., et al. (2022). "Estradiol treatment in young postmenopausal women with self-reported cognitive complaints: Effects on cholinergic-mediated cognitive performance." Human psychopharmacology 37(5): e2838.
	Objective: Older women are at increased risk of developing Alzheimer's disease compared to men. One proposed reason is that following menopause there is a decline in estrogens. Estrogens are important for cholinergic functioning and attenuate the impact of cholinergic antagonists on cognitive performance in postmenopausal women. Self-reported or subjective cognitive complaints in middle or older age may represent a harbinger of cognitive decline and those who endorse cognitive complaints appear more likely to develop future cognitive impairment. However, the response of individuals with cognitive complaints after menopause to estrogen and the relationship to cholinergic functioning has not been investigated. This study investigated the effect of estrogen treatment using 17β-estradiol on cognitive performance following anticholinergic blockade in postmenopausal women and the relationship of this interaction with the level of self-reported (subjective) postmenopausal cognitive complaints.; Methods: Forty postmenopausal women (aged 50-60 years) completed a 3-month treatment regimen of either 1 mg oral estradiol or placebo. Participants then completed four challenge days in which they completed cognitive and behavioral tasks after one of four cholinergic antagonist drug conditions (oral mecamylamine (MECA), intravenous scopolamine, combined MECA and scopolamine, or PLC).; Results: Compared to PLC, the estradiol treated group performed worse on attention tasks under cholinergic challenge including the choice reaction time task and the critical flicker fusion task. In addition, participants who endorsed greater cognitive complaints showed reduced performance on the N-back working memory task, regardless of whether they received estradiol treatment.; Conclusions: The findings of this study indicate that estradiol treatment was unable to mitigate anticholinergic blockade in postmenopausal women with subjective cognitive complaints, and worsened performance on attention tasks. Moreover, the present study suggests that greater levels of cognitive complaints following menopause may be associated with an underlying decline in cholinergic function that may manifest as an inability to compensate during working memory tasks. (© 2022 John Wiley & Sons Ltd.)

Constantine Ginger, D., et al. (2019). "Endometrial safety of low-dose vaginal estrogens in menopausal women: a systematic evidence review." Menopause (New York, N.Y.) 26(7): 800-807.
	Objective: The aim of the study was to systematically review studies that evaluated endometrial hyperplasia or cancer incidence with unopposed vaginal estrogens.; Methods: PubMed and EMBASE were searched from inception to August 2017 for relevant articles and abstracts. Bibliographies of review articles and abstracts of major women's health medical meetings were examined. Eligible studies (independently reviewed by 4 authors) had to report menopausal vaginal estrogen use and endometrial histology, or incidence of endometrial hyperplasia or cancer.; Results: Of 5,593 abstracts from the literature search and 47 articles from other sources, 36 articles and 2 abstracts were eligible, describing 20 randomized controlled studies, 8 interventional studies, and 10 observational studies. Collectively, the studies did not support an increased risk of endometrial hyperplasia or cancer with low-dose vaginal estrogens. Rates of endometrial cancer and hyperplasia were 0.03% and 0.4%, respectively, from 20 randomized controlled trials (2,983 women) of vaginal estrogens. Overall, reports of endometrial hyperplasia were observed with various doses and durations and appeared sporadic (except 1.25 mg conjugated equine estrogens), consistent with endometrial hyperplasia rates in the general population. A Denmark registry study was an exception and may be of limited applicability to the United States. The Women's Health Initiative Observational Study showed no association (1.3 cases/1,000 women-years with vaginal estrogens versus 1.0/1,000 women-years for nonuse).; Conclusion: This systematic review supports the use of low-dose vaginal estrogens for treating vulvar and vaginal atrophy in menopausal women without a concomitant progestogen. This review does not support increased endometrial hyperplasia or cancer risk with low-dose, unopposed vaginal estrogens; however, longer-term, real-world data are needed.

Conte, E., et al. (2023). "An evaluation of longitudinal quality of life in patients with advanced-stage cancer seeking care at Canadian naturopathic oncology clinics: Outcomes from the Canadian/US Integrative oncology study." Journal of Complementary and Integrative Medicine 20(1): eA5.
	Background: Quality of life (QOL) is an important outcome for patients with advanced cancer as treatments are usually not curative. Naturopathic medicine is a form of complementary care often used by patients to support QOL; however, data on efficacy is limited. In this study, we evaluated longitudinal QOL and symptom burden in a subset of participants from the Canadian/US Integrative Oncology Study. Method(s): Participants from CUSIOS (stage IV breast/colorectal or stage III/IV ovarian/pancreatic cancer) seen at a Canadian naturopathic clinic were included in this sub-study. QOL and symptom burden were characterized using the European Organization for Research and Treatment of Cancer's (EORTC) Quality of Life Questionnaire C30, Edmonton Symptom Assessment Scale (ESAS), and Measure Yourself Concerns and Wellbeing (MYCAW) questionnaire. Assessments were completed six times over 36months. Within person changeswere analyzedwith unadjusted paired t-tests using the Bonferroni correction for multiple assessments. Result(s): 104 participants were enrolled with 97 included in the analyses. Questionnaire completion rates were 91% at baseline, 63-73% between months 3 and 24, and 52% atmonth 36 (excluding those deceased). Compared to baseline, EORTC global health improved at all timepoints with 3/6 reaching statistical significance; ESAS total symptom score improved at all timepoints with 5/6 reaching statistical significance;MYCAWconcerns improved at all timepointswith 5/6 reaching statistical significance. Improvements were above the minimum important difference. Conclusion(s): Longitudinal QOL and symptom data in advanced cancer patients receiving naturopathic care was collected, but response rates were suboptimal. QOL and symptom burden generally improved; however, due to the lack of a control group, it is not clear if this was a result of naturopathic medicine. More rigorous and well-controlled research is needed..

Contegiacomo, A., et al. (2021). "Uterine Myomas: Endovascular Treatment." Seminars in ultrasound, CT, and MR 42(1): 13-24.
	Uterine fibroids embolization is a safe and effective organ sparing treatment for fibroid-related symptoms based on a broad range of published evidence including randomized-controlled trials. Indication to treatment is usually the presence of symptomatic uterine fibroids. In this review, a systematic search of journal articles relevant to the treatment of symptomatic uterine fibroids was conducted, with a special focus on the indication to treatment, technique, procedural outcomes and pain control. All clinical trials published in English language, representing original research, and reporting clinical outcomes associated with interventions for the management of symptomatic uterine fibroids were considered. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Contreras, N.-A., et al. (2022). "Fertility-Sparing Approaches in Atypical Endometrial Hyperplasia and Endometrial Cancer Patients: Current Evidence and Future Directions." International Journal of Molecular Sciences 23(5).
	Endometrial cancer (EC) is the fourth most common cancer in women in developed countries. Although it is usually diagnosed in postmenopausal women, its incidence has increased in young women, as well in recent decades, with an estimated rate of 4% in those under 40 years of age. Factors involved in this increase, particularly in resource-rich countries, include delayed childbearing and the rise in obesity. The new molecular classification of EC should help to personalize treatment, through appropriate candidate selection. With the currently available evidence, the use of oral progestin either alone or in combination with other drugs such as metformin, levonorgestrel-releasing intrauterine devices and hysteroscopic resection, seems to be feasible and safe in women with early-stage EC limited to the endometrium. However, there is a lack of high-quality evidence of the efficacy and safety of conservative management in EC. Randomized clinical trials in younger women and obese patients are currently underway.

Cooijmans, K. H. M., et al. (2022). "Daily mother-infant skin-to-skin contact and maternal mental health and postpartum healing: a randomized controlled trial." Scientific Reports 12(1): 10225.
	This randomized controlled trial examined the effects of a daily hour of mother-infant skin-to-skin contact (SSC) during the first five postnatal weeks, compared to care-as-usual, on maternal depressive (primary outcome), anxiety, stress, fatigue, pain, and delivery-related post-traumatic stress symptoms (PTSS). Prenatal symptom severity and touch discomfort were examined as moderators. Mothers and full-term infants were randomly allocated to SSC or care-as-usual conditions and followed during the first postnatal year. For the total group (intention-to-treat analyses), care-as-usual mothers showed an increase of anxiety symptoms from week 2 to 12, while SSC mothers displayed a stability of anxiety symptoms. Also, care-as-usual mothers showed an initial decrease in fatigue followed by an increase, while SSC mothers showed a decrease from week 2 to 12. In per-protocol analyses, including only the SSC dyads who adhered to SSC guidelines, findings on anxiety, but not fatigue, were replicated. No SSC effects were found for depressive, stress, and pain symptoms. No moderator, dose-response, or 52-week follow-up effects were found. PTSS were low with little variation; consequently, analyses were discontinued. Daily SSC in healthy mother-infant dyads may reduce anxiety and fatigue symptoms, but not depressive, stress, and pain symptoms, during the early postpartum period. Replication studies are recommended.

Coomarasamy, A., et al. (2020). "Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence." American Journal of Obstetrics and Gynecology 223(2): 167-176.
	Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coomarasamy, A., et al. (2020). "Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT." Health technology assessment (Winchester, England) 24(33): 1-70.
	Background: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage.; Objectives: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding.; Design: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding.; Setting: A total of 48 hospitals in the UK.; Participants: Women aged 16-39 years with early pregnancy bleeding.; Interventions: Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation.; Main Outcome Measures: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective.; Results: A total of 4153 women from 48 hospitals in the UK received either progesterone ( n = 2079) or placebo ( n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation.; Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.; Trial Registration: Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326.; Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.; Competing Interests: Jane P Daniels declares membership of the Clinical Trials Unit Standing Advisory Committee. Mee akshi Choudhary declares m mbership of Health Technology Assessment (HTA) Maternal, Newborn and Child Health (MNCH) Panel and the HTA Prioritisation Committee. Jane E Norman declares membership of the HTA MNCH Panel, that she currently receives funding from the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, that she participates in a Data Monitoring and Ethics Committee for GlaxoSmithKline plc (Brentford, UK) and that she is a paid consultant for Dilafor AB (Solna, Sweden). She was a member of the HTA and EME Editorial Board from 2012 to 2014. Caroline Overton declares that she was a Mylan clinical educator for general practitioner education about hormone replacement therapy and incorporated private practice in April 2017 (now called Bristol Women’s Clinic Ltd).

Cooper Miranda, C., et al. (2019). "Using Matching-Adjusted Indirect Comparisons and Network Meta-analyses to Compare Efficacy of Brexanolone Injection with Selective Serotonin Reuptake Inhibitors for Treating Postpartum Depression." CNS drugs 33(10): 1039-1052.
	Background: Brexanolone injection, the first therapy approved by the US FDA for the treatment of postpartum depression (PPD) in adults, has been shown to produce a significantly greater decrease in the Hamilton Rating Scale for Depression (HAM-D) total score than placebo in randomised controlled trials (RCTs) of women with PPD.; Objectives: Given the rapid effect of brexanolone injection (within 60 h) sustained throughout the length of the trials (30 days), we sought to compare its efficacy data against selective serotonin reuptake inhibitors (SSRIs), the class of antidepressants most commonly prescribed for PPD, using HAM-D and Edinburgh Postnatal Depression Scale (EPDS) outcomes from currently available RCTs.; Methods: We extracted data from 26 studies identified in a systematic literature review of pharmacological and pharmacological/nonpharmacological combination therapies in PPD. Six studies were suitable to form evidence networks through which to perform indirect treatment comparisons (ITCs) of HAM-D and EPDS outcomes between brexanolone and SSRIs. Having assessed the comparability and suitability of the available evidence for analysis, we discovered significant heterogeneity in the study designs, most notably in the placebo arms of the trials. We therefore conducted matching-adjusted indirect comparisons (MAICs) between brexanolone and the placebo arms of comparator studies, subsequently using the MAIC results of brexanolone versus placebo, and results for SSRIs versus placebo, to form ITCs of brexanolone versus SSRIs at three separate time points-day 3, week 4 and last observation. ITCs were calculated as the differences in change from baseline (CFB) in HAM-D and, separately, CFB in EPDS, between treatments, and reported with 95% confidence intervals (CIs).; Results: For all time points, MAICs showed larger differences in CFB for brexanolone compared with SSRIs. Differences (95% CIs) between brexanolone and SSRIs were 12.79 (8.04-17.53) [day 3], 5.87 (- 1.62 to 13.37) [week 4] and 0.97 (- 6.35 to 8.30) [last observation] for the HAM-D. For the EPDS, the differences in CFB were 7.98 (5.32-10.64) [day 3], 6.35 (3.13-9.57) [week 4] and 4.05 (0.79-7.31) [last observation]. Other analytical approaches are also presented to demonstrate the similarity of results, using a network meta-analysis approach, and the importance of using the MAIC method to control for the important heterogeneity between placebo arms.; Conclusions: Acknowledging the limitations of ITCs and this evidence base, when compared with SSRIs, these analyses suggest that brexanolone demonstrated larger differences in CFB for both patient- and clinician-reported PPD outcomes and at all investigated time points after adjusting for differences between placebos in the included studies.

Coopmans, L., et al. (2023). "Surgical Management of Gestational Trophoblastic Disease." Gynecologic and Obstetric Investigation.
	Background: Gestational trophoblastic disease (GTD) is a rare pregnancy-related condition consisting of premalignant and malignant forms arising from proliferation of trophoblastic cells. The malignant forms are collectively referred to as gestational trophoblastic neoplasia (GTN) and are highly sensitive to chemotherapy. However, surgical procedures remain indispensable in the diagnosis and treatment of GTD. Objective(s): The aim of this review was to summarize surgical interventions in the treatment of GTD and GTN. We reviewed indications, efficacy, possible complications, and oncological outcomes of surgery. Method(s): Three searches were performed in the databases of PubMed, Embase, and the Cochrane Library to create an up-to-date overview of existing literature on the following subjects: (1) the role of primary hysterectomy in GTD and GTN; (2) the role of second curettage in GTD and GTN; (3) fertility sparing surgery in GTN; (4) surgical management of metastases. Included articles originated from the time period 1952-2022. Articles written in English, Spanish, and French were included. Outcome(s): Thirty-eight articles were found and selected. Surgical evacuation through suction curettage is most used and advised in the treatment of GTD. A second curettage could be beneficial in patients with low hCG levels and low FIGO scores. In women who have completed their families, primary hysterectomy might be considered as the risk of subsequent GTN is lower than after suction curettage. In case of the rare forms of GTN (epithelioid trophoblastic tumor or placental site trophoblastic tumor) surgical tumor resection remains the most important step in treatment. Data on fertility sparing surgery in GTN are scarce and this treatment should be considered experimental. Conclusion and Outlook: Surgery remains an important part of treatment of GTD and is sometimes indispensable to achieve curation. Further collection of evidence is needed to determine treatment steps. © 2023 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

Cope, A. G., et al. (2020). "Nonsurgical radiologic intervention for management of abdominal wall endometriosis: A systematic review and meta-analysis." Journal of Endometriosis and Pelvic Pain Disorders 12(1): 41-50.
	Objective: To describe reported outcomes of nonsurgical radiologic interventions for abdominal wall endometriosis in comparison with surgery where available. Data sources: A systematic search of Ovid Medline, Embase, PubMed, and Cochrane Controlled Register of Trials was performed from inception to January 2019 with no language restrictions. Study eligibility criteria: Studies were included if they evaluated a nonsurgical intervention in women with symptomatic abdominal wall endometriosis with both comparative and noncomparative study designs. Study appraisal and synthesis methods: Titles and abstracts were reviewed for relevance, and full-text articles were obtained and evaluated for inclusion, all in duplicate. Meta-analysis was performed when possible using a fixed effects model. Result(s): Of the 114 records reviewed, 16 full-text articles were assessed and 7 were included in analysis. The standard mean difference between pre- and post-intervention pain scores was similar between ultrasound-guided high-intensity focused ultrasound (USgHIFU) (-3.00; 95% confidence interval -3.34, -2.66) and cryoablation (-3.93; 95% confidence interval -5.73, -2.12). The mean percent decrease in lesion size following intervention was similar between USgHIFU (-61.38%; 95% confidence interval -78.64%, -44.11%), and cryoablation (-88.16%; 95% confidence interval -83.90%, -55.06%). When compared with surgical excision, mean length of stay was 2.78 days less in the nonsurgical intervention group (95% confidence interval -3.78, -1.79). Conclusion(s): Both USgHIFU and cryoablation are effective at reducing pain scores and lesion size in abdominal wall endometriosis. Mean length of stay was significantly less following a nonsurgical radiologic intervention for abdominal wall endometriosis compared with surgery. More studies are needed comparing complication and recurrence rates between nonsurgical radiologic interventions for abdominal wall endometriosis and surgery.Copyright © The Author(s) 2020.

Coquan, E., et al. (2021). "CABOCOL-01 trial: a single-arm phase II study assessing safety and efficacy of Cabozantinib for advanced or metastatic cervical carcinoma after platinum treatment failure." BMC Cancer 21(1): 1054.
	BACKGROUND: Cervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor. In addition to chemotherapy, bevacizumab, an antiangiogenic agent, has recently demonstrated its efficacy in this setting. Cabozantinib is an oral small molecule tyrosine kinase inhibitor that exhibits potent inhibitory activity against several receptor tyrosine kinases that are known to influence tumor growth, metastasis, and angiogenesis. The main targets of Cabozantinib are VEGFR2, MET and AXL. It is currently approved for the treatment of metastatic renal cell carcinoma, hepatocellular carcinoma and medullary thyroid carcinoma. Given its angiogenic properties associated with growth factor receptors inhibition, Cabozantinib represents a potential active treatment in cervical carcinoma. In this context, we propose to assess the efficacy and safety of cabozantinib monotherapy in advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. METHODS: This study is a single-arm two-stage multicenter phase II aiming to simultaneously assess efficacy and safety of Cabozantinib among advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. The main criterion will be based on both safety and clinical efficacy by conducting a Bryant-and-Day design. Safety endpoint is the proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE V.5.0) occurring up to one month after the end of treatment. Efficacy endpoint is the proportion of patients with disease control rate 3 months after Cabozantinib initiation. A patients' self-reported quality of life evaluation is also planned, as well as the investigation of nutritional outcomes. Cabozantinib will be administered at the daily dose of 60 mg given orally, without interruption until disease progression or discontinuation for any cause. DISCUSSION: Cabozantinib is a promising drug for patients with advanced/metastatic cervical cancer where few therapeutics options are available after failure to platinum-based regimen metastatic CC. It appears challenging to assess the interest of Cabozantinib in this indication, taking into account the potential toxicity of the drug. TRIAL REGISTRATION: NCT04205799 , registered "2019 12 19". PROTOCOL VERSION: Version 3.1 dated from 2020 08 31.

Coquoz, A., et al. (2019). "Impact of micronized progesterone on body weight, body mass index, and glucose metabolism: a systematic review." Climacteric : the journal of the International Menopause Society 22(2): 148-161.
	In women, body weight increases with age. Often menopausal hormone therapy (MHT) is blamed for enhancing this effect. In recent years, the debate on bioidentical MHT including micronized progesterone (MP) has increased. Among others, the question has been raised of whether MHT containing MP has an impact on body weight and glucose metabolism. Based on a systematic literature review on the impact of MHT containing MP on body weight, body mass index (BMI), and glucose metabolism, the following conclusions can be drawn: estrogens combined with MP (1) either do not change or reduce body weight in normal weight postmenopausal women, (2) do not change BMI in normal and overweight postmenopausal women, (3) do not change or improve fasting serum glucose levels in (non-)diabetic postmenopausal women, (4) do not change or improve fasting serum insulin levels in (non-)diabetic postmenopausal women, and (5) do not have an impact on serum glycated hemoglobin in postmenopausal diabetic women. This beneficial effect is probably mostly due to the estrogen MHT component.

Coracao Hospital, d. and S. Paulo University of (2023). Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer.
	This study hypothesizes that patients who persist with cell-free human papillomavirus deoxyribonucleic acid (cfHPV-DNA) plasma expression at the end of standard treatment, can derive the benefit of using adjuvant chemotherapy in locally advanced cervical cancer (CC). After standard treatment based on concomitant chemoradiotherapy regime, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Patients who have positive research for plasma cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Corbally, L. and M. Wilkinson (2021). "The effect of mindfulness-based interventions on stress, depression and anxiety during the perinatal period in women without pre-existing stress, depressive or anxiety disorders: A systematic review and meta-analysis of controlled trials." Mindfulness 12(10).
	OBJECTIVES: The objective of this systematic review and meta-analysis was to examine controlled trial evidence for the effectiveness of mindfulness-based interventions on stress, anxiety and depression in the perinatal period in women without pre-existing mental health issues. METHODS: Six databases were searched for studies exploring the effects of mindfulness-based interventions on mental health outcomes of women during the perinatal period. Quality of both controlled trial meeting inclusion criteria were assessed using a tool specifically designed for meta-analyses of mindfulness-based interventions. Effect sizes were extracted for measures of mindfulness, depression, stress and anxiety outcomes. Effects were pooled in separate meta-analyses for all outcomes except anxiety which lacked sufficient studies. RESULTS: Twelve studies were analysed. Pooled effects suggest that mindfulness-based interventions cause small but clear increases in mindfulness and reductions in depression in women without pre-existing disorders. Effects of mindfulness-based interventions on other outcomes were unclear and confounded by heterogeneity. CONCLUSIONS: Available controlled trial evidence suggests that mindfulness-based interventions improve mindfulness and decrease symptoms of depression during pregnancy in women without pre-existing mental health issues and might be a useful approach to prevent or attenuate the development of depression in the perinatal period. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Corbaux, P., et al. (2023). "Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis." European journal of cancer (Oxford, England : 1990) 191: 112966.
	Background: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors.; Methods: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model.; Results: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established.; Conclusion: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.; Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benoit You has received compensation for his advisory role for MSD, AstraZeneca, GSK-TESARO, BAYER, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology and Merck Serono. Rosalind Glasspool declares personal financial interests for her advisory role for AstraZeneca, MSD, Clovis Oncology, GSK/Tesaro and Immunogen. She also has received compensation for speaker fees and funding to attend medical conferences from TSK/Tesaro, and consultancy fees from Sotio. Anna Tinker has received honoraria from AstraZeneca and Eisai, a research grant from AstraZeneca and declares her role within the advisory committee and speaker’s bureau of GSK. Kristina Lindemann has received compensation for her advisory role for GSK, AstraZeneca and Eisai, and a research grant from GSK. Isabelle Ray-Coquard declares personal fees from AstraZeneca, GSK, Clovis Oncology, Mersana, Deciphera, Eisai, Amgen, BMS, Onxena, Aravive and Roche. Mansoor Raza Mirza has received compensation for his advisory role for AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche and Zailab. He also received financial interest from Karyopharm as a member of the board of directors and related to stocks and shares. Julien Péron declares compensation from Fab’entech for advisory role; from Eisai as invited speaker, consultant and member of board of directors and from Lilly as invited speaker. He also has received research funding from Roche. Iain McNeish has received compensation for his advisory role for AstraZeneca, Clovis Oncology, GSK, Roche and ScannCell. All remaining authors have declared no conflicts of interest. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Corbaz, F., et al. (2023). "'connEcted caesarean section': creating a virtual link between MOthers and their infanTs to ImprOve maternal childbirth experieNce - study protocol for a PILOT trial (e-motion-pilot)." BMJ Open 13(6): e065830.
	Introduction: One-third of mothers rate their childbirth as traumatic. The prevalence of childbirth-related post-traumatic stress disorder (CB-PTSD) is 4.7%. Skin-to-skin contact is a protective factor against CB-PTSD. However, during a caesarean section (CS), skin-to-skin contact is not always feasible and mothers and infants are often separated. In those cases, there is no validated and available solution to substitute this unique protective factor. Based on the results of studies using virtual reality and head-mounted displays (HMDs) and studies on childbirth experience, we hypothesise that enabling the mother to have a visual and auditory contact with her baby could improve her childbirth experience while she and her baby are separated. To facilitate this connection, we will use a two-dimensional 360° camera filming the baby linked securely to an HMD that the mother can wear during the end of the surgery.; Methods and Analysis: This study protocol describes a monocentric open-label controlled pilot trial with minimal risk testing the effects of a visual and auditory contact via an HMD worn by the mother airing a live video of her newborn compared with treatment-as-usual in 70 women after CS. The first 35 consecutive participants will be the control group and will receive the standard care. The next 35 consecutive participants will have the intervention. The primary outcome will be differences in maternal childbirth experience (Childbirth Experience Questionnaire 2) at 1-week postpartum between the intervention and control groups. Secondary outcomes will be CB-PTSD symptoms, birth satisfaction, mother-infant bonding, perceived pain and stress during childbirth, maternal anxiety and depression symptoms, anaesthesiological data and acceptability of the procedure.; Ethics and Dissemination: Ethics approval was granted by the Human Research Ethics Committee of the Canton de Vaud (study number 2022-00215). Dissemination of results will occur via national and international conferences, peer-reviewed journals, public conferences and social media.; Trial Registration Number: NCT05319665.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Corbeau, A., et al. (2021). "Correlations between bone marrow radiation dose and hematologic toxicity in locally advanced cervical cancer patients receiving chemoradiation with cisplatin: a systematic review." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 164: 128-137.
	Patients with locally advanced cervical cancer (LACC) treated with chemoradiation often experience hematologic toxicity (HT), as chemoradiation can induce bone marrow (BM) suppression. Studies on the relationship between BM dosimetric parameters and clinically significant HT might provide relevant indices for developing BM sparing (BMS) radiotherapy techniques. This systematic review studied the relationship between BM dose and HT in patients with LACC treated with primary cisplatin-based chemoradiation. A systematic search was conducted in Embase, Medline, and Web of Science. Eligibility criteria were treatment of LACC-patients with cisplatin-based chemoradiation and report of HT or complete blood cell count (CBC). The search identified 1346 papers, which were screened on title and abstract before two reviewers independently evaluated the full-text. 17 articles were included and scored according to a selection of the TRIPOD criteria. The mean TRIPOD score was 12.1 out of 29. Fourteen studies defining BM as the whole pelvic bone contour (PB) detected significant associations with V10 (3/14), V20 (6/14), and V40 (4/11). Recommended cut-off values were V10 > 95-75%, V20 > 80-65%, and V40 > 37-28%. The studies using lower density marrow spaces (PBM) or active bone marrow (ABM) as a proxy for BM only found limited associations with HT. Our study was the first literature review providing an overview of articles evaluating the correlation between BM and HT for patients with LACC undergoing cisplatin-based chemoradiation. There is a scarcity of studies independently validating developed prediction models between BM dose and HT. Future studies may use PB contouring to develop normal tissue complication probability models.; Competing Interests: Conflicts of interest Erasmus MC Radiotherapy has research agreements with Accuray and Elekta. NH reports to have received research grants from the Dutch Cancer Society and Varian. MH reports to have received research grants from Varian Medical Systems and clinical advisory membership of Accuracy. RN reports to have received research grants outside the submitted work from Dutch Cancer Society, Dutch Research Council, Elekta, Varian Medical Systems, and Accuracy. The other authors have declared no conflicts of interest. (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Corbeau, A., et al. (2021). "Protect: Prospective phase-ii-trial evaluating adaptive proton therapy for cervical cancer to reduce the impact on morbidity and the immune system." Cancers 13(20): 5179.
	External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient's quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). How-ever, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2 ), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy . Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Corchero-Falcón, M. D. R., et al. (2023). "Risk Factors for Working Pregnant Women and Potential Adverse Consequences of Exposure: A Systematic Review." International journal of public health 68: 1605655.
	Objective: To assess the risk factors perceived as stressors by pregnant women in the work environment and the possible adverse consequences of such exposure for the normal development of pregnancy. Methods: Systematic review, guided by the PRISMA guidelines, and using Pubmed, Web of Science, Dialnet, SciELO, and REDIB databases. Methodological quality was assessed using the critical appraisal tools for non-randomised studies of the Joanna Briggs Institute. Results: A total of 38 studies were included. The main risk factors found in the work environment of pregnant women were chemical, psychosocial, physical-ergonomic-mechanical factors, and other work-related factors. The main adverse consequences of exposure to these factors include low birth weight, preterm birth, miscarriage, hypertension and pre-eclampsia, as well as various obstetric complications. Conclusion: During pregnancy, working conditions that are considered acceptable in normal situations may not be so during this stage due to the major changes that occur during pregnancy. Many obstetric effects may have an important impact in the mother's psychological status; therefore, it is important to optimise working conditions during this stage and to reduce or eliminate possible risks.

Cordova, O., et al. (2022). "A prospective, randomized, placebo-controlled pilot trial investigating telomere length dynamics and ovarian function in patients with diminished ovarian reserve (DOR) after danazol treatment." Human Reproduction 37(Supplement 1): i483-i484.
	Study question: Could the administration of a synthetic steroid -danazolfor 3 months reactivate telomerase activity and lengthen telomeres in patients with DOR? Summary answer: Danazol treatment resulted in an increase of the mean leukocyte telomeric length (TL) but did not improve fertility results after the nearest ovarian stimulation (OS). What is known already: A primary molecular cause of aging is telomere attrition, given that the accumulation of critically short telomeres leads organ dysfunction. Telomere shortening can be counteracted by the telomerase enzyme, which is responsible for adding deoxyribonucleotides to the linear ends of chromosomes. In patients with DOR, TL in granulosa cells (GCs) is short and telomerase activity is absent, compromising their proliferative capacity. Previuos studies have shown that estrogens can activate telomerase gene transcription through estrogen-responsive elements located in the promoter of the telomerase gene. Therefore, telomere attrition could be reduced in patients with DOR upon telomerase reactivation. Study design, size, duration: This blinded, placebo-controlled pilot trial was carried out at IVIRMA Madrid clinic between February 2020 and February 2022. The study included 12 patients with DOR (AMH<2ng/ml) which were randomized to danazol or placebo. Patients had 12 visits for health supervision and in vitro fertilization (IVF) treatment. Both groups received danazol (400mg per day) or placebo for 3 months. As control group, 7 patients with normal ovarian reserve (AMH-2ng/ml) were included. Participants/materials, setting, methods: In both groups, blood samples were collected prior (PT) and after the treatment (AT). Luteinized GCs and blood samples were obtained during oocyte retrieval, after OS. Leukocytes were purified in Ficoll gradients and then, evaluated for TL and TRF1 levels by Quantitative Fluorescent in Situ Hybridization followed by image acquisition using high resolution confocal microscope. IVF parameters were assessed according to IVIRMA standard protocols. Main results and the role of chance: A total of 19 women were recruited: 5 in the placebo group (39.8+/-2.7 years), 7 in Danazol group (41.0+/-3.0 years) and 7 in control group (39.5+/-3.0 years). The Danazol group showed a trend to higher mean TL in leukocytes after the treatment (108.2+/-37.4 versus 99+/-13.2 a.u., AT vs PT). Interestingly, the percentage of long telomeres also increased with treatment (15.5+/-0.0 versus 10.8+/-8.1 a.u., AT vs PT). In addition, there was a decrease of the percentage of critically short telomeres (15.7+/-0.0 versus 20.8+/-9.9 a.u. AT vs PT). In the placebo group, mean leukocyte TL and the percentage of long and short telomeres remained constant. These findings suggest that telomeres lengthen after Danazol treatment. The protein levels of TRF1, a shelterin involved in telomere protection, were similar in both Danazol and placebo groups. Regarding fertility, there were no differences in the number of antral follicles, total and MII oocytes, fertilization rate and blastocyst formation. The control group had, as expected, signficantly higher mean follicle number after OS when compared with Danazol (16.0+/-1.4 and 0.7+/-0.9, P<0.0001) and placebo (16.0+/-1.4 and 5.0+/-3.8, p=0.0127) groups, and higher numbers of total oocytes retrieved (p=0.006; control and Danazol, and p=0.007; control and placebo). Limitations, reasons for caution: Firstly, the number of patients included in the study is limited due to strict inclusion/exclusion criteria. Secondly, because follicle growth can take up to 150 days, danazol effects could be noticeable at later OS and not only in the first OS, which was the only one studied here. Wider implications of the findings: Since telomeres seem to elongate in blood samples after Danazol treatment in DOR patients, we could hypothesize that this may have a positive impact for general health, including the ovaries. Thus, danazol therapy might help improving IVF outcomes, perhaps at later OS.

Corinna, C., et al. (2021). "The effect of mother/infant group music classes on postnatal depression – a systematic review protocol."
	
Cork University, C., et al. (2021). The LYSA (Linking You to Support and Advice) Trial.
	No Results Available Other: Survivorship Clinic Assessments|Other: Survivorship Clinic Nurse Resource|Other: Survivorship Clinic Dietitian Resource Number of patients enrolled in the clinic.|Reasons for not enrolling to the study.|Reasons for not completing the intervention (drop out).|Percentage of adherence to the intervention completing ePROs surveys|Number of patients who partake in healthcare professional consultations after ePRO data triggers.|Average consultation time in the Womens Survivorship Clinic.|Change from Baseline in cancer-related symptoms scores assessed by Patient-Reported Outcomes.|Change from Baseline in Health related-Quality of Life Questionnaire (QLQ) scores assessed by European Organization for the Research and Treatment of Cancer (EORTC).|Change from Baseline in Health related-Quality of Life Questionnaire (QLQ) Breast Cancer Module scores assessed by European Organization for the Research and Treatment of Cancer (EORTC).|Change from Baseline in Health related-Quality of Life Questionnaire (QLQ) Cervical Cancer Module scores assessed by European Organization for the Research and Treatment of Cancer (EORTC).|Change from Baseline in Health related-Quality of Life Questionnaire (QLQ) Endometrial Cancer Module scores assessed by European Organization for the Research and Treatment of Cancer (EORTC).|Change from Baseline in EuroQol 5-Level 5-Dimensions quality-adjusted life-year version (EQ-5D-5L-QALY) scores.|Change from Baseline in Appraisal Self-Care Agency-R scores (15 items).|Change from Baseline in adjuvant endocrine therapy medication adherence.|Assessment of Usability and Satisfaction of the survivorship clinic will be assessed by the Usability and Satisfaction Scale (Lewis, 1995).|Experience and opinions from patients, HCP and wider stakeholders about the Women Survivorship Study including the clinic.|Number of resources used by each patient with a cancer related symptom to evaluate the economic impact.|Change from Baseline in Diet intake scores from multiple 24-hour recalls, complemented by a Food Frequency Questionnaire (FFQ).|Change from Baseline in Diet quality scores from The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) standardised scoring system (Shams-White et al 2019).|Change from Baseline in BMI scores.|Change from Baseline in Lean Body Mass (LBM) scores.|Change from Baseline in waist circumference scores.|Change from Baseline in Segmental Body Composition scores assessed measured by Body Composition Monitor bioimpedance spectroscopy (BIS).|Change from Baseline in muscle strength scores on handgrip measurements.|Change from Baseline in Nutritional risk scores assessed by the Malnutrition Screening Tool (MST). The higher the score, the higher risk of malnutrition. Female Not Applicable 200 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Supportive Care R19258|WHI19CON|BCR-2019-09-ICS-UCC April 2024

Cornelisse, S., et al. (2021). "Comparing the cumulative live birth rate of cleavage-stage versus blastocyst-stage embryo transfers between IVF cycles: a study protocol for a multicentre randomised controlled superiority trial (the ToF trial)." BMJ Open 11(1): e042395.
	INTRODUCTION: In vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen-thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited. METHODS AND ANALYSIS: We have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients' treatment burden. ETHICS AND DISSEMINATION: The study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL 6857).

Coronado, P. J., et al. (2024). "Eligibility criteria for using menopausal hormone therapy in breast cancer survivors: a safety report based on a systematic review and meta-analysis." Menopause 31(3): 234-242.
	Importance Menopause hormone therapy (MHT) effectively alleviates menopausal symptoms. However, it is generally not recommended for breast cancer survivors, although the scientific evidence is scarce. Objective This study aimed to establish eligibility criteria for use of the MHT in breast cancer survivors based on a systematic review and meta-analysis of the literature. Evidence Review We conducted exhaustive literature searches until June 2022 in MEDLINE, The Cochrane Library, and EMBASE, using a tailored strategy with a combination of controlled vocabulary and search terms related to breast cancer survivors and MHT. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed the risk of bias using the Cochrane and Risk of Bias in Non-randomized Studies - of Interventions tools. The quality of the evidence was graded according to grading quality of evidence and strength of recommendations criteria (A, high; B, moderate; C, low; and D, very low). We categorized MHT use into four levels: category 1 (no restrictions on use), category 2 (the benefits outweigh the risks), category 3 (the risks generally outweigh the benefits), and category 4 (MHT should not be used). Findings A total of 12 studies met the eligibility criteria. Analysis of the three randomized clinical trials using combined MHT or tibolone revealed no significant differences concerning tumor recurrence (relative risk [RR], 1.46; 95% CI, 0.99-2.24). A combined analysis of randomized clinical trials, prospective, and retrospective trials found no elevated risk of recurrence (RR, 0.85; 95% CI, 0.54-1.33) or death (RR, 0.91; 95% CI, 0.38-2.19). The eligibility criteria for patients with hormone receptor (HR)-positive tumors fell into categories 3B and 3C for combined MHT or estrogen alone and 4A for tibolone. For HR-negative tumors, the category was 2B and 2C. Conclusions and Relevance Our findings suggest that MHT could be a viable treatment alternative for breast cancer survivors experiencing menopausal symptoms, especially those with HR-negative tumors. Personalized management is recommended for each peri/postmenopausal woman facing a diminished quality of life because of menopause symptoms. Further randomized trials are needed before considering changes to current standards of care. Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Coronado, P. J., et al. (2023). "Pharmacological interactions and menopausal hormone therapy: a review." Menopause 30(8): 873-880.
	Importance and Objective Menopausal hormone therapy (HT) is widely used, and there are several statements of international scientific societies to guide prescribers; however, a summary of existing literature about possible drug interactions with HT does not exist, although many midlife women take medications for other conditions. Therefore, our objective was to create a document that presents and synthesizes the most relevant interactions. The impact of the interaction itself and the number of candidates for HT who are likely to use other treatments are considered based on the best available evidence. Methods A systematic review was performed to determine the best evidence of interaction effects on relevant outcomes of interest for decision making. A working framework was developed to formulate explicit and reasoned recommendations according to four predefined categories for coadministration: (1) can be used without expected risks, (2) acceptable use (no evidence of negative interaction), (3) alternative treatment should be considered, and (4) nonuse without express justification. The project protocol was registered in the Open Science Framework platform (doi: 10.17605/OSF.IO/J6WBC) and in PROSPERO (registration number CRD42020166658). Results Studies targeting our objective are scarce, but 23 pharmacological groups were assigned to one of the predefined categories of recommendation for concomitant use of HT. Vaginal HT was assigned to category 1 for 21 of the analyzed pharmacological groups. For oral and transdermal HT (estrogen-only or combined) and tibolone, there were 12 pharmacological groups assigned to category 1, 12 to category 2, 5 to category 3, and 4 to category 4. Results are shown in crossed-tables that are useful for counseling and prescription. Discussion and conclusions Available evidence of HT interactions with other drugs is scarce and mainly indirect. It comes from biological plausibility, knowledge of extensive concomitant use without reported incidents, and/or extrapolation from hormonal contraception, but there are pharmacological groups in all categories showing that information is useful. These eligibility criteria summarize it and can help in the decision process of HT coadministration with other drugs. Decisions should be taken based on these recommendations but also individualized risk/benefit evaluation, according to underlying pathology, patient's clinical requirements, and the existence or nonexistence of alternatives.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Corporation, G. and G. O. G. Foundation (2022). Efficacy & Safety of Olvi-Vec and Platinum-doublet + Bevacizumab Compared to Platinum-doublet + Bevacizumab in Platinum-Resistant/Refractory Ovarian Cancer (OnPrime, GOG-3076).
	No Results Available Biological: olvimulogene nanivacirepvec|Drug: Platinum chemotherapy: carboplatin (preferred) or cisplatin|Drug: Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin|Drug: Bevacizumab (or biosimilar) Progression-free survival (PFS) by RECIST 1.1 in the Intention-to-Treat (ITT) population (all randomized participants regardless of whether they received any dose of treatment)|Incidence of Treatment-emergent Adverse Events in the ITT population|Duration of Response (DOR) by RECIST 1.1 in the ITT population|PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm)|PFS by iRECIST in the ITT population|Overall Response Rate (ORR) by RECIST 1.1 in the ITT population|Overall Survival in the ITT population Female Phase 3 186 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Olvi-Vec-022|GOG-3076 October 2026

Corr, B., et al. (2023). "Treatment-related adverse events in a randomized trial in stage three and four ovarian cancer testing patient-specific dendritic cell vaccines loaded with tumor antigens from self-renewing autologous tumor cells (1258)." Gynecologic Oncology 176(Supplement 1): S164.
	Objectives: The purpose of this study was to determine the clinical effects of a patient-specific therapeutic ovary cancer vaccine consisting of autologous dendritic cells (DC) loaded with autologous tumor antigens (ATA) from self-renewing autologous cancer cells. The objectives of the double-blind 2:1 randomized trial were to determine: (1) the feasibility and efficiency of manufacturing DC-ATA, (2) adverse events associated with DC-ATA injections compared to injections of autologous monocytes (MC) as a control arm, and (3) survival in the two arms. This report focused on the safety comparison. Method(s): A multi-institutional, double-blind, randomized phase II clinical trial was designed to determine treatment-related adverse events (TEAE) associated with the granulocyte-macrophage colony-stimulating factor (GM-CSF) and DC-ATA compared to GM-CSF plus MC. Key eligibility criteria were: (1) primary diagnosis of stage III or IV ovary epithelial cancer, (2) successful cell culture of ovarian cancer cells, (3) successful monocyte collection by leukapheresis, (4) completion of primary multimodality therapy and (5) ECOG of 0 or 1 at the time of randomization. After completing primary systemic therapy, patients were stratified by whether they had residual disease and then randomized 2:1 to vaccine or control arms. Randomization occurred about 7 months after the initial surgery. IL-4 and GM-CSF were used to differentiate monocytes into DC, which were incubated with the lysate of cultured ovarian cancer cells as the ATA source. Patients in the control arm received cryopreserved autologous MC from their leukapheresis product. Each dose was admixed with 500 mug GM-CSF at the time of subcutaneous injections at weeks 1, 2, 3, 8, 12, 16, 20, and 24. Fisher's exact test was used to compare proportions, and t-test to compare means. Result(s): The trial was halted by the sponsor after 45 patients were randomized. All patients had an opportunity to receive all 8 possible injections and an additional month of follow-up for safety assessment. The median age was 61 years (range: 38 to 84). ECOG status was 0 for 30, 1 for 13, and 2 for two subjects. Thirty-two were stage III, and 13 were stage IV at the time of surgery. Thirty patients received neoadjuvant therapy. Forty-five patients received 333 injections; 29 patients received DC-ATA, and 16 received MC. No patient discontinued treatment because of toxicity, but 1 patient in the MC arm was hospitalized after the eighth dose for refractory urticaria that necessitated high-dose corticosteroids. Most TEAE possibly associated with investigational treatment were mild to moderate in severity. Most common were local injection site reactions (58%), malaise-fatigue (44%), rash and/or pruritus (36%), headache (27%), myalgias (27%), arthralgias (27%), and bone discomfort (27%). There were no differences in the proportions of these events between study arms. The number of TEAE ranged from 0 to 24 (mean 7.9) in the DC-ATA arm and 1 to 12 (mean 6.5) in the MC arm (P = 0.309). There were 4 grade 3 TEAE possibly due to study treatment: 2 episodes of hypertension, 1 headache, and 1 rash and pruritus, including urticaria. There were 5 grade 3 and 1 grade 4 TEAE due to cytopenias in patients receiving concurrent chemotherapy, and 2 grade 3 due to abdominal/pelvic pain that was attributed to ovarian cancer or prior surgery. There was no difference in the proportion of grade 3 or 4 by study arm (P = 1.00). Conclusion(s): DC-ATA was well-tolerated, with no differences between study arms. Most TEAE attributed to study products are probably due to GM-CSF rather than differences between DC-ATA and MC.Copyright © 2023

Corrado, G., et al. (2023). "Patterns of recurrence in FIGO stage IB1-IB2 cervical cancer: Comparison between minimally invasive and abdominal radical hysterectomy." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49(11): 107047.
	Objective: Aim of our study was to evaluate whether the different laparotomic (ARH) or minimally invasive (laparoscopic and robotic) approaches (MIS) in FIGO stage IB1-IB2 cervical cancer, present different patterns of recurrence of the disease. The secondary endpoint of the study was the evaluation of the variables most involved with the risk of relapse and therefore lower DFS and OS.; Material and Methods: The study enrolled patients with definitive histological diagnosis of squamous or adenocarcinoma stage IB1-IB2 cervical cancer who underwent minimally invasive or abdominal radical hysterectomy from 2001 to 2018.; Results: The study enrolled 360 patients and 59 patients (16.4 %) reported a disease relapse. The data showed that ARH group was not associated with different recurrence patterns than MIS group (p = 0.14). Moreover, there was no statistically significant difference regarding DFS (p = 0.52) and OS (p = 0.29) between the ARH group and the MIS group.; Conclusions: MIS, in FIGO stage IB1-IB2 cervical cancer, is not associated with different relapse patterns compared to ARH, nor with a higher risk of distance metastasis and finally, without significant difference in term of DFS and OS. More studies are needed to determine the factors that modify the site of relapse.; Competing Interests: Declaration of competing interest No conflict of interest is disclosed. (© 2023 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Cory, R., et al. (2021). "HIIT’ing or MISS’ing the optimal management of polycystic ovary syndrome: a systematic review and meta-analysis of high- versus moderate-intensity exercise prescription."
	
Costa Kamilla, R. and B. Metzger Patrick (2020). "Endovascular treatment of uterine myomatosis: a systematic review." Jornal vascular brasileiro 19: e20190149.
	Uterine Artery Embolization (UAE) is a noninvasive alternative to open surgery for treatment of uterine myomatosis. This study aims to analyze the efficacy and safety of UAE in these cases. A systematic review was carried out of studies available on the Medline (via PubMed) and the LILACS and PEDro (via the Biblioteca Virtual em Saúde) databases. The searches found 817 studies, 7 of which were selected according to the eligibility criteria (analytical, longitudinal, retrospective, or prospective studies), with a total of 367 patients studied. The variables analyzed and the characteristics of the studies included were collated and input to a database. Rates of volume reduction of the uterus and the dominant myoma were 44.1% and 56.3%, respectively. Mean rate of complete infarction of the dominant myoma was 88.6% (82-100%). The mean number of complications observed was 15±8.6 cases, most of which were classified as minor, and no deaths were recorded. The mean number of re-interventions in absolute values was 12.2±15.5 cases. Therefore, in the literature analyzed, uterine artery embolization is an effective procedure with a low rate of complications for treatment of uterine leiomyomatosis.; Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article.

Costello Michael, F., et al. (2019). "A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome." The Australian & New Zealand Journal of Obstetrics & Gynaecology 59(6): 867-873.
	Background: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated.; Aims: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018.; Materials and Methods: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages.; Results: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed.; Conclusion: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS. (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Cote, G. M., et al. (2022). "A phase 1b lead-in to a randomized phase 2 trial of lurbinectedin plus doxorubicin in leiomyosarcoma (LMS)." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Single agent or combination chemotherapy regimens, typically including doxorubicin or gemcitabine, represent standard of care options for first- and second-line therapy in patients (pts) with metastatic LMS. However, response rates (ORR) and progression-free (PFS)/overall survival (OS) remain poor. Lurbinectedin (PharmaMar S.A. and Jazz Pharmaceuticals) uniquely binds DNA, inducing DNA double strand breaks leading to apoptosis and delaying progression through phase S/G2 of the cell cycle. Lurbinectedin is a novel structural analog of trabectedin with improved toxicity profile, potency, and pharmacokinetics. In a prior pilot study, we showed that the combination of lurbinectedin and doxorubicin (L+D) was safe, with early signs of clinical activity, particularly in LMS. Thus, we designed this investigator-initiated/investigator-sponsored phase 1b lead-in to optimize doses of L+D, to be followed by a randomized (1:1) phase 2 study of L+D versus doxorubicin monotherapy in anthracycline- naive LMS. Method(s): Pts age > 18 years with locally advanced or metastatic, unresectable LMS (non-GIST soft-tissue sarcoma histologies allowed in Phase 1b), without prior anthracycline or lurbinectedin/ trabectedin, ECOG PS < 3, measurable disease by RECIST 1.1, and normal organ function, are eligible. Phase 1b dosing will include a fixed dose of lurbinectedin and two dose levels of doxorubicin. The Phase 1b lead-in follows a standard 3+3 design where dose escalation will occur if 0/3 or 1/6 patients experience a dose-limiting toxicity (DLT). Tumor assessments are conducted every two cycles. Once the recommended phase 2 dose (RP2D) is confirmed, Phase 2 will be initiated. Fifty pts will be randomized 1:1 including doxorubicin +/- lurbinectedin. Randomization will be stratified by uterine v. non-uterine origin of LMS. Pts progressing on single agent doxorubicin will be allowed to cross over to lurbinectedin monotherapy. The Phase 2 primary endpoint is PFS. Secondary endpoints include disease control rate, ORR, OS, PFS2 (for doxorubicin monotherapy patients who cross to lurbinectedin monotherapy). Archival tumor, germline DNA, and ctDNA will be collected for correlative studies exploring genomic markers of sensitivity/resistance. We will provide respective point estimate along with 90% confidence interval for each of the arms. Log-rank test will be performed to test the difference in survival (both PFS and OS) between groups. Regression analyses of survival data will be based on the Cox proportional hazards model. The first pt in dose-level 1 of the Phase 1b lead-in was enrolled in February 2022.

Coutzac, C., et al. (2022). "Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial." Digestive and Liver Disease 54(10): 1335-1341.
	Background: Immune checkpoint inhibitors (ICI) targeting Programmed death-1 (PD-1) have shown their efficacy in advanced MSI/dMMR (microsatellite instability/deficient mismatch repair) tumors. The MSI/dMMR status predicts clinical response to ICI. The promising results evaluating ICI in localized MSI/dMMR tumors in neoadjuvant setting need to be confirmed in MSI/dMMR solid tumors. The aim of the IMHOTEP trial is to assess the efficacy of neoadjuvant anti-PD-1 treatment in MSI/dMMR tumors regarding the pathological complete response rate. Method(s): This study is a prospective, multicenter, phase II study including 120 patients with localized MSI/dMMR carcinomas suitable for curative surgery. A single dose of pembrolizumab will be administered before the surgery planned 6 weeks later. Primary objective is to evaluate the efficacy of neoadjuvant pembrolizumab according to pathological complete tumor response. Secondary objectives are to assess safety, recurrence-free survival and overall survival. Ancillary studies will assess molecular and immunological biomarkers predicting response/resistance to ICI. First patient was enrolled in December 2021. Discussion(s): The IMHOTEP trial will be one of the first clinical trial investigating perioperative ICI in localized MSI/dMMR in a tumor agnostic setting. Assessing neoadjuvant anti-PD-1 is mandatory to improve MSI/dMMR patient's outcomes. The translational program will explore potential biomarker to improve our understanding of immune escape and response in this ICI neoadjuvant setting.Copyright © 2022 The Authors

Cowan, M., et al. (2021). "Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer, an NCCN phase II trial." Gynecologic Oncology 163(1): 57‐63.
	OBJECTIVE: Tivozanib is a potent selective pan‐vascular endothelial growth factor receptor tyrosine kinase inhibitor with a long half‐life. This study assessed its activity in patients with recurrent, platinum‐resistant ovarian, fallopian tube or primary peritoneal cancer (OC). METHODS: This open‐label phase II study used a Simon's two‐stage design. Eligible patients had recurrent, platinum‐resistant OC and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily for 21 days in a 28‐day cycle. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression‐free survival (PFS), overall survival (OS), and toxicity assessment. RESULTS: Thirty‐one patients were enrolled, and 30 were treated. The median age was 59.5 years, and median number of prior regimens was 4 (range 1‐9). Twenty‐four patients were evaluable for response, and four (16.7%) achieved a partial response (PR; ORR = 16.7%). An additional fourteen (58.3%) patients had stable disease (SD). The clinical benefit rate (PR + SD) was 75.0%, and the median duration of objective response was 5.7 months. For all patients on trial, the median PFS was 4.1 months (95% confidence interval (CI): 1.7‐5.8) and OS 8.6 months (95% CI: 5.4‐12.5). There were no treatment‐related deaths. Serious adverse events occurred in 13.3% of patients and included small intestinal perforation or obstruction and stroke. Grade 3‐4 adverse events occurred in 60% of patients, including hypertension (26.7%) and fatigue (10%). CONCLUSIONS: Tivozanib is effective in patients with recurrent OC, with moderate toxicity and no treatment‐related deaths, supporting its further development.

Coward, J. I., et al. (2021). "Maximum Tolerated Dose and Anti-Tumor Activity of Intraperitoneal Cantrixil (TRX-E-002-1) in Patients with Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer: Phase I Study Results." Cancers 13(13).
	Survival outcomes in ovarian cancer are poor. The aims of this Phase I progressive design study (NCT02903771) were to evaluate the maximum tolerated dose (MTD), tolerability, and antitumor activity of Cantrixil-a novel third-generation benzopyran molecule-in patients (n = 25) with advanced, recurrent/persistent epithelial ovarian, primary peritoneal, or fallopian tube cancer. All had completed ≥ 2 prior regimens; 3 (12%) had platinum-refractory disease, and 17 (68%) had platinum-resistant disease. Following intraperitoneal (IP) port placement, patients received weekly IP Cantrixil in 3-week cycles as monotherapy (Cycles 1-2), and then in combination with intravenous (IV) chemotherapy (Cycles 3-8). Part A (dose escalation) enrolled 11 patients in 6 dose-level cohorts. An MTD of 5 mg/kg was established with dose-limiting toxicity of ileus. Most treatment-related adverse events were gastrointestinal. Across Parts A and B (dose expansion), 16 (64%) patients received ≥ 1 3-week Cantrixil cycle, and had ≥ 1 post-baseline efficacy measurement available. The results show promising anti-tumor activity in monotherapy (stable disease rate of 56%) and in combination with IV chemotherapy (objective response rate of 19%, disease control rate of 56%, and median progression-free survival of 13.1 weeks). The molecular target and mechanism of action of Cantrixil are yet to be confirmed. Preliminary analysis of stem cell markers suggests that IP Cantrixil might induce ovarian cancer stem cell death and sensitize cells to standard chemotherapy, warranting further evaluation.

Coyle Meaghan, E., et al. (2021). "Licorice (Glycyrrhiza spp.) and jujube (Ziziphus jujuba Mill.) formula for menopausal symptoms: Classical records, clinical evidence and experimental data." Complementary Therapies in Clinical Practice 44: 101432.
	Objectives: This study sought to determine the most common oral herbal formula for menopausal symptoms in classical Chinese medicine textbooks and investigate its clinical effectiveness and potential mechanisms of action.; Methods: The most common formula used for menopause-like symptoms in past eras was identified from the Encyclopedia of Traditional Chinese Medicine. A systematic review of randomized controlled trials (RCTs) was undertaken and findings from relevant experimental studies were summarized.; Results: Licorice (Glycyrrhiza spp.) and jujube (Ziziphus jujuba Mill.) formula (LJF) was used in 63 of the 175 citations (36%) in the classical literature. Evidence from four RCTs showed that while LJF may improve sleep symptoms, there is insufficient evidence to provide recommendations for clinical practice. Experimental studies showed sedative, antidepressant-like, estrogenic and antiprogestogenic actions.; Conclusions: LJF has a long history of use for menopause-like symptoms, but further research is needed to confirm its clinical effects and guide clinical decision-making. (Copyright © 2021. Published by Elsevier Ltd.)

Coyne, E., et al. (2020). "Acknowledging cancer as a family disease: A systematic review of family care in the cancer setting." European Journal of Oncology Nursing 49.
	Purpose: Family members are a part of the team to improve the outcomes of the person with cancer. Families require support and information to optimise their care, however, their needs are often unacknowledged and within clinical areas there is a lack of family focused interventions. Studies highlight families' needs but lack a family representation. The aim was to explore research with family as the unit-of-care during cancer treatment. Method: The Pickering systematic quantitative literature review method; a 15-step process from searching, database development and analysis was followed. Research published 2008-2019 within databases: MEDLINE, SCOPUS, PsycINFO, Cochrane, CINAHL; key words, 'family* or caregiver*, and cancer*, neoplasm* and coping*, distress* in November 2019. Quality assessment completed using Mixed Methods Appraisal Tool, descriptive quantitative analysis and thematic analysis. Results: Studies involving patients and family members were included in the review (N = 73). The analysis identified participants had a mean age of 58 years and primarily lung, breast or prostate cancer. Over 80% were from America and European countries; 93% had a dyad sample, quantitative studies (76%). There was eight intervention studies between four to sixteen weeks long, focused on family wellbeing. Themes described the impact of cancer on the whole family, the importance of communication between family members, and resources for family members. Conclusion: The review identified four main scales and optimum intervention styles. Family research in the adult cancer needs to focus on intervention studies, increase international focus and inclusion of other family members such as children, friends and older adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Cozzolino, M., et al. (2020). "How vitamin D level influences in vitro fertilization outcomes: results of a systematic review and meta-analysis." Fertility and Sterility 114(5): 1014-1025.
	Objective: To investigate the impact of serum vitamin D level on in vitro fertilization (IVF) outcomes.; Design: Systematic review and meta-analysis.; Setting: Not applicable.; Patients: Infertile women undergoing conventional IVF or intracytoplasmic sperm injection (ICSI).; Interventions: Systematic search of PubMed, MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science from inception until July 2019 with cross-checking of references from relevant articles in English. Vitamin D levels were categorized into three groups: deficient (<20 ng/mL), insufficient (20-30 ng/mL), and replete (>30 ng/mL). Before starting the data extraction, we registered the review protocol in PROSPERO (CRD42019134258).; Main Outcome Measures: We consider clinical pregnancy rate (CPR), live birth rate (LBR), and/or ongoing pregnancy rate (OPR) as primary outcomes. Likewise, the miscarriage rate was considered as a secondary outcome.; Results: Primary analysis showed that women with a replete level of vitamin D had higher CPR and LBR/OPR compared to those with a deficient of insufficient level of vitamin D. However, sensitivity analysis led to non-significant differences between the comparators for CPR (odds ratio 0.71, 95% confidence interval 0.47-1.08, I2 = 61%) and OPR/LBR (odds ratio 0.78, 95% confidence interval 0.56-1.08], I2 = 61%). Also, for miscarriage a statistically different rate was not reached.; Conclusion: Serum vitamin D levels do not influence IVF outcomes in terms of CPR, LBR/OPR, and miscarriage rate. Future large cohort studies are warranted to determine whether the threshold of vitamin D affects reproductive outcomes. Currently, there is a lack of consensus between the appropriate vitamin D threshold to predict reproductive outcomes compared to the one established for bone health.; Prospero Number: CRD42019134258. (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Cozzolino, M., et al. (2020). ""Delayed start" gonadotropin-releasing hormone antagonist protocol in Bologna poor-responders: A systematic review and meta-analysis of randomized controlled trials." European Journal of Obstetrics, Gynecology, and Reproductive Biology 244: 154-162.
	To evaluate the effectiveness of delay start protocol in improving the success of in vitro fertilization (IVF) in poor responders according to Bologna's criteria. Only randomized controlled trial (RCT) of infertile women undergoing a single IVF/ICSI cycle with ovarian stimulation protocol based on daily injections with delay start protocol or a conventional antagonist protocol were included in this systematic review and meta-analysis. The review protocol was registered in PROSPERO before starting the data extraction (CRD42019128284). Primary outcome was clinical pregnancy rate. Ongoing pregnancy rate, miscarriage rate, number of oocytes, number of MII oocytes, stimulation length, gonadotropin amount and cancellation rate were considered as secondary outcomes. Four randomized controlled trials were included with a total number of 380 participants. 189 patients were included in the delayed start protocol and 191 were allocated to the comparison group. The results showed a significant higher clinical pregnancy rate (CPR) in patients allocated to the intervention. Data from all studies failed to detect a statistical difference between groups in terms of ongoing pregnancy rate (OPR), miscarriage rate (MR), Total-Oocyte, MII-Oocyte and Total-Embryos. Gonadotropin amount (GA) was significantly lower in the intervention group in comparison to controls, with no difference in stimulation length (SL) and cancelled cycle (CC). Delayed start GnRH-antagonist protocol may reduce GA and improve CPR in poor ovarian responder according to Bologna criteria. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cozzolino, M., et al. (2022). "The Effect of Uterine Adenomyosis on IVF Outcomes: a Systematic Review and Meta-analysis." Reproductive sciences (Thousand Oaks, Calif.) 29(11): 3177-3193.
	To investigate the impact of uterine adenomyosis on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) clinical outcomes and also to evaluate the impact of gonadotropin-releasing hormone agonist (GnRHa) and surgical treatments. Infertile women with adenomyosis undergoing conventional IVF or ICSI were compared with women without adenomyosis. Fertility outcomes were evaluated in two patients with adenomyosis untreated and treated surgically or medically therapy. The review protocol was registered in PROSPERO (CRD42020214586). We consider the live birth rate (LBR) as the primary outcome. The analysis showed that women with adenomyosis had lower LBR (OR 0.59, 95% CI 0.37-0.92, p = 0.02), clinical pregnancy rate (OR 0.66, 95% CI 0.48-0.90), and ongoing pregnancy rate (OR 0.43, 95% CI 0.21-0.88) compared to those without adenomyosis, and miscarriage rate was higher in women with adenomyosis (OR 2.11, 95% CI 1.33-3.33). Surgical treatment increases natural conception in women with adenomyosis although the paucity of data (only two studies), and conversely, treatment with GnRHa does not increase the IVF outcomes. Women with adenomyosis have decreased IVF clinical outcomes. Pretreatment with the use of long-term GnRHa could not be beneficial, even though only three studies were included in the meta-analysis. The major part of the studies has not divided focal and diffuse adenomyosis, and this represents a relevant source of bias: studies conducted with standardized diagnostic criteria for adenomyosis are still needed to determine if the different clinical presentations of such condition could compromise IVF outcomes. (© 2021. Society for Reproductive Investigation.)

Cozzolino, M., et al. (2020). "Therapy with probiotics and synbiotics for polycystic ovarian syndrome: a systematic review and meta-analysis." European journal of nutrition 59(7): 2841-2856.
	Objective: Several randomized controlled trials (RCTs) have investigated the use of probiotic/synbiotic in PCOS patients, without clarifying the real use in clinical practice. The aim of this meta-analysis was to evaluate the effectiveness of probiotics and synbiotics on metabolic, hormonal and inflammatory parameters of PCOS.; Methods: Electronic databases (MEDLINE, Scopus, EMBASE, ScienceDirect, The Cochrane Database of Systematic Reviews and ClinicalTrials.gov) were searched from their inception until May 2019. The study protocol was registered in PROSPERO with number CRD42018111534. Randomized controlled trials (RCTs) of PCOS's women undergoing therapy at least 8 weeks with probiotics or synbiotics or without therapy were included. The primary outcomes were changes in anthropometric parameters, glucose/insulin metabolism, lipid profile, sex hormones profile, inflammation markers.; Results: 587 patients were included in nine RCT. The administration of probiotic/synbiotic were associated with a significant improvement in FPG, FBI, HOMA I-R, BMI. It also modified Ferriman-Gallway, serum triglycerides, serum testosterone, hs-CRP, NO, TAC, GSH, and MDA. Subgroup analysis of the type of intervention showed that probiotics were associated with greater testosterone and FPG reduction; synbiotics administration resulted in a more pronounced decrease of the FBI. Subgroup analyses on the duration of therapy showed that, probiotic/synbiotic administration had a significantly greater effect on QUICK-I in the case of women with 12-weeks of therapy than in the 8-weeks therapy group. Nevertheless, we did not observe any significant difference was observed in terms of FBI, HOMA-IR, and FPG.; Conclusions: Probiotics and synbiotics seem to either an effect on/influence metabolic, hormonal and inflammatory parameters, or can influence them. Consequently, it could lead to an improvement of fertility in PCOS.

Cozzolino, M., et al. (2022). "Correction to: Therapy with probiotics and synbiotics for polycystic ovarian syndrome: a systematic review and meta‑analysis." European journal of nutrition 61(4): 2233-2235.
	
Craciunas, L., et al. (2022). "Hormone therapy for uterine and endometrial development in women with premature ovarian insufficiency." The Cochrane Database of Systematic Reviews 10: CD008209.
	Background: Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear.; Objectives: To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI.; Search Methods: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2021. We also checked references of included studies, and contacted study authors to identify additional studies.; Selection Criteria: We included randomised controlled trials (RCTs) investigating the effect of various hormonal preparations on the uterine development of women diagnosed with POI.; Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcome was uterine volume; secondary outcomes were endometrial thickness, endometrial histology, uterine perfusion, reproductive outcomes, and any reported adverse events.; Main Results: We included three studies (52 participants analysed in total) investigating the role of various hormonal preparations in three different contexts, which deemed meta-analysis unfeasible. We found very low-certainty evidence; the main limitation was very serious imprecision due to small sample size. Conjugated oral oestrogens versus transdermal 17ß-oestradiol We are uncertain of the effect of conjugated oral oestrogens compared to transdermal 17ß-oestradiol (mean difference (MD) -18.2 (mL), 95% confidence interval (CI) -23.18 to -13.22; 1 RCT, N = 12; very low-certainty evidence) on uterine volume, measured after 12 months of treatment. The study reported no other relevant outcomes (including adverse events). Low versus high 17ß-oestradiol dose We are uncertain of the effect of a lower dose of 17ß-oestradiol compared to a higher dose of 17ß-oestradiol on uterine volume after three or five years of treatment, or adverse events (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes. Oral versus vaginal administration of oestradiol and dydrogesterone We are uncertain of the effect of an oral or vaginal administration route on uterine volume and endometrial thickness after 14 or 21 days of administration (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes (including adverse events).; Authors' Conclusions: No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI. (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Creinin, M. D., et al. (2022). "Heavy Menstrual Bleeding Treatment With a Levonorgestrel 52-mg IUS." Obstetrics and Gynecology 139(SUPPL 1): 34S.
	INTRODUCTION: Prior levonorgestrel 52-mg intrauterine system (IUS) studies for heavy menstrual bleeding (HMB) limited body mass index (BMI) and included only parous women. We evaluated outcomes in a population without BMI or parity restrictions. METHOD(S): We performed an institutional review board- approved, Phase 3 study of Liletta for HMB. Participants had up to three screening cycles with collection of study-specific sanitary products for alkaline hematin blood loss measurement. We enrolled those with two menses >=80 mL (values averaged for baseline blood loss) and placed the IUS. Participants collected sanitary products used during months 3 and 6 post-placement for blood loss measurement if any bleeding occurred. We evaluated median absolute change in blood loss in participants with at least one follow-up assessment and compared BMI and parity outcomes using Wilcoxon rank sum tests. RESULT(S): Of the 105 enrolled participants, 68 (65%) were White, 25 (24%) were Black, 47 (45%) were obese (BMI >=30), and 29 (28%) were nulliparous. Baseline mean blood loss ranged from 73 mL to 520 mL (median, 143 mL; interquartile range [IQR], 112-196 mL), with median 3-month (n586) and 6-month (n581) values of 9.5 mL (IQR, 2.5-22.9 mL) and 3.8 mL (IQR, 0-10.1 mL), respectively. The median percentage decreases per participant were 93% (IQR, 82-98%) and 97% (IQR, 90-100%), respectively. At six months, median decreases in non-obese (n546) and obese (n535) participants did not differ (97% [IQR, 90-100%] and 97% [IQR, 89-100%], respectively; P5.73) with similar findings for nulliparous (n525) and parous (n556) participants (97% [IQR, 92-99%] and 97.5% [IQR, 89-100%], respectively; P5.74). Discontinuations included 4 (4%) expulsions, +/- (6%) removals for bleeding/cramping, and 12 (11%) participant choice/lost to follow-up/consent withdrawal. CONCLUSION(S): Levonorgestrel 52-mg IUS reduces blood loss more than 90% for most users with HMB regardless of BMI and parity.

Creinin Mitchell, D., et al. (2023). "Heavy Menstrual Bleeding Treatment With a Levonorgestrel 52-mg Intrauterine Device." Obstetrics and Gynecology 141(5): 971-978.
	Objective: To evaluate heavy menstrual bleeding treatment outcomes with levonorgestrel 52-mg intrauterine device (IUD) use in participants without body mass index (BMI) or parity restrictions.; Methods: Investigators included participants aged 18-50 years with no pelvic or systemic pathology causing heavy menstrual bleeding at 29 U.S. centers in a prospective trial. Participants had up to three screening cycles with menstrual product collection for alkaline hematin blood-loss measurements. Investigators enrolled those with two menses with blood loss of 80 mL or more (values averaged for baseline blood loss), placed the IUD, and followed participants for up to six 28-day cycles. Participants collected any menstrual products used during cycles 3 and 6 for blood-loss measurement. We evaluated outcomes in participants with at least one follow-up assessment for the primary outcome of median absolute blood-loss change and, secondarily, treatment success , defined as the proportion with a final measured blood loss less than 80 mL and at least 50% reduction from baseline. We evaluated exploratory outcomes of differences in blood-loss changes by BMI and parity using Wilcoxon rank sum test.; Results: Of 105 enrolled participants, 47 (44.8%) had obesity (BMI 30.0 or higher) and 29 (27.6%) were nulliparous. Baseline mean blood loss ranged from 73 to 520 mL (median 143 mL, interquartile range 112-196 mL). Eighty-nine (84.8%) had at least one evaluable follow-up evaluation. Participants had median (interquartile range) absolute blood-loss decreases at cycles 3 (n=86) and 6 (n=81) of 93.3% (86.1-97.7%) and 97.6% (90.4-100%), respectively. At cycle 6, participants without obesity (n=43) and with obesity (n=38) had similar median [interquartile range] decreases (97.6% [91.8-100%] and 97.5% [90.3-100%], respectively; P =.89), with comparable findings for nulliparous (n=25) and parous (n=56) participants (97.0% [91.7-99.1%] and 98.1% [89.9-100%], respectively; P =.43). Treatment success occurred in 81.8% (95% CI 74.2-89.4%) of 99 participants, excluding those with no outcomes due to lost to follow-up or consent withdrawal, and did not vary by BMI or parity. The most common adverse events leading to discontinuation were bleeding or cramping (n=6 [5.7%]) and expulsion (n=5 [4.8%]).; Conclusion: This levonorgestrel 52-mg IUD reduces blood loss by more than 90% over 6 months compared with baseline for most users with heavy menstrual bleeding.; Funding Source: Medicines360.; Clinical Trial Registration: ClinicalTrials.gov , NCT03642210.; Competing Interests: Financial Disclosure Mitchell D. Creinin has received speaking honoraria from Gedeon Richter, Mayne and Organon. He has served on the Advisory Boards for Evofem, Fuji Pharma, Gedeon Richter, GlaxoSmithKline, Mayne, Merck & Co., OLIC, Organon, and Searchlight. He has been a Consultant for Estetra SRL, Libbs, Mayne, and Medicines360, and his university department receives contraceptive research funding for Dr. Creinin from Chemo Research SL, Evofem, HRA Pharma, Medicines360 (includes support for medical and safety oversight of this study), Merck & Co., and Sebela. Kurt T. Barnhart has served on the Advisory Board for Merck & Co. His university department receives contraceptive research funding from Bayer HealthCare, Medicines360, Merck & Co., and Sebela. Lori M. Gawron's university department receives contraceptive research funding from Bayer HealthCare, Cooper Surgical, Medicines360, Merck & Co., Sebela, Femasys, and Teva. David Eisenberg has served on the Advisory Board for Merck & Co. He has been a consultant for Evofem Biosciences and FemaSys. He has received honoraria from Omnia Education. His university department receives contraceptive research funding from Evofem Biosciences, Medicines360, Merck & Co., Myovant and Sebela. R. Garn Mabey has received research funding from Allergan, Medicines360, Mithra, and Sebela. Jeffrey T. Jensen has received payments for consulting from Bayer Healthcare, Evofem, Hope Medicine, Foundation Consumer Healthcare, Mayne Pharma, ViiV Healthcare, and erapeuticsMD. OHSU has received research support from AbbVie, Bayer Healthcare, Daré, Estetra SPRL, Hope Medicine, Medicines360, Merck, Myovent, and Sebela. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Creutzberg Carien, L. (2022). "Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features." ClinicalTrials.gov.
	The p53abn‐RED trial (NCT05255653‐1) is an international, multicenter, phase III randomised trial wherein adjuvant chemoradiation followed by olaparib for two years is compared to adjuvant chemoradiation. The MMRd‐GREEN trial (NCT05255653‐2) is an international, multicenter, phase III randomised trial wherein adjuvant pelvic external beam radiotherapy combined with and followed by durvalumab for one year is compared to adjuvant pelvic external beam radiotherapy. The NSMP‐ORANGE trial (NCT05255653‐3) is an international, multicenter, phase III randomised trial wherein adjuvant pelvic external beam radiotherapy followed by progestogens for two years is compared to adjuvant chemoradiation. The POLEmut‐BLUE trial (NCT05255653‐4) is an international, multicenter, single arm, phase II trial wherein safety of de‐escalation of adjuvant therapy is investigated: no adjuvant therapy for stage I‐II disease and no adjuvant therapy or pelvic external beam radiotherapy only for stage III disease. The overarching RAINBO research project will combine the data and tumor material of the four RAINBO clinical trials to perform translational research and compare molecular profile‐based adjuvant therapy to standard adjuvant therapy in terms of effectiveness, toxicity, quality of life and cost utility.

Crisp Carol, D., et al. (2023). "Complementary Approaches for Military Women with Chronic Pelvic Pain: A Randomized Trial." Journal of Integrative and Complementary Medicine 29(1): 22-30.
	Introduction: Active duty (AD) women suffer with chronic pelvic pain (CPP) while providers tackle diagnoses and treatments to keep them functional without contributing to the opioid epidemic. The purpose of this randomized trial was to determine the effectiveness of noninvasive, self-explanatory mindfulness-based stress reduction (MBSR) or self-paced healthy lifestyle (HL) interventions on CPP in AD women. Methods: A 6-week, interventional prospective study with AD women aged 21-55 years at Mountain Home (MTHM), Idaho, was conducted. Women were randomly assigned to MBSR ( N = 21) or HL ( N = 20) interventions. The primary outcome was pain perception. The secondary outcomes were depression and circulating cytokine levels. Results: Women in the MBSR group exhibited reduced pain interference ( p < 0.01) and depression ( p < 0.05) alongside decreased interleukin (IL)-4 ( p < 0.05), IL-6 ( p < 0.05), eotaxin ( p < 0.05), monocyte chemoattractant protein-1 ( p = 0.06), and interleukin-1 receptor antagonist (IL-1ra) ( p < 0.01) and increased vascular endothelial growth factor ( p < 0.05). Women in the HL group did not have changes in pain; however, they did exhibit reduced depression ( p < 0.05) alongside decreased granulocyte-macrophage colony-stimulating factor ( p < 0.05) and increased tumor necrosis factor alpha ( p < 0.05), stromal cell-derived factor-1 ( p < 0.01), and IL-1ra ( p < 0.01). Conclusions: AD women receiving MBSR or HL had reduced depression scores and altered circulating cytokine levels; however, only those receiving MBSR had reduced pain perception. Findings support MBSR as an effective and viable behavioral treatment for AD women suffering from CPP and provide premise for larger randomized controlled studies. Clinical Trial Registration: MOCHI-An RCT of mindfulness as a treatment for CPP in AD Women NCT04104542 (September 26, 2019).

Cristian de Guirior, M. n., et al. (2022). "Comparation of pregnancy and newborn rate after different endometrioma treatment modalities (ablative, excisional, sclerotherapy)."
	
Critchlow Annabel, J., et al. (2023). "The role of estrogen in female skeletal muscle aging: A systematic review." Maturitas 178: 107844.
	Aging is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle aging compared to males, potentially due to menopause, when the production of endogenous sex hormones declines. This systematic review aims to investigate the current knowledge about the role of estrogen in female skeletal muscle aging. A systematic search of MEDLINE Complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of estrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. estrogen therapy) to normal estrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesized in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal women, postmenopausal women had reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signaling pathways remains unclear. Some studies suggest a beneficial effect of estrogen therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review point toward a potential negative effect of estrogen deficiency on aging skeletal muscle, but further mechanistic evidence is needed to clarify its role.; Competing Interests: Declaration of competing interest The authors declare that they have no competing interest. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Critelli, P., et al. (2023). "Outcomes and toxicity in re-irradiation of gynecologic cancer: Systematic review of the Italian association of radiation and clinical oncology (AIRO)." Gynecologic Oncology 179: 33-41.
	Aims: The aim of this study was to provide a literature review on the efficacy and safety of reirradiation(re-I) of locoregional recurrences in gynecological malignancies.; Methods: A computerized literature search was performed in 4 electronic databases (1993-2020). Random-effects models and a tendency towards high heterogeneity (Cochran Q chi-square test and the I 2 statistic) were used. A meta-analysis technique over single and multi-arm studies was performed to determine the pooled acute and late toxicity rate ≥ G3, locoregional control (LC), and overall survival (OS).; Results: Out of 178 articles, only 18 articles accounting for 820 patients (pts) met the inclusion criteria. Outcomes were evaluable for 522 patients. Subgroup analyses highlighted moderate to high heterogeneity among studies. BT (Brachytherapy) showed a 2y OS of 63% (95% CI, 55 to 71 p = 0,36) and 5y OS of 42% (95% CI, 35 to 50, p = 0,43) with 1y-2y-3y LC of 74 (95% CI, 62 to 75, p = 0.04)49% (95% CI, 40 to 58, p = 0.38) and 48% (95% CI, 39 to 58, p = 0,45) respectively. Chemotherapy does not improve SBRT outcomes: BT showed a G3- G4 toxicities rate was of26% (95% CI: 8-49%); studies on SBRT re-I showed a G3-G4 toxicity around of 20% if combined with CHT, and <10 when alone.; Conclusion: A large heterogeneity among studies was revealed, but showing promising results in terms of safety and feasibility. BT resulted the best kind of radiation therapy delivery in terms of clinical outcome and comparable to the SBRT technique in terms of toxicities.; Competing Interests: Declaration of Competing Interest The authors declares no conflict of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Crockett, K. L., et al. (2019). "A Review of the Effects of Physical Therapy on Self-Esteem in Postpartum Women With Lumbopelvic Dysfunction." Journal of Obstetrics and Gynaecology Canada 41(10): 1485-1496.
	This study sought to determine the impact of physical therapy for lumbopelvic dysfunction on self-esteem in postpartum women. Systematic searches were carried out in CINAHL, Embase, PsycINFO, Medline (OVID), Cochrane, and Web of Science by a health sciences librarian using various combinations of subject headings and key words. A dual review process was used first to assess titles and abstracts and then to examine the full text. Conflicts were resolved through discussion or a third reviewer as needed. Dual data extraction was completed using a standardized collection form. Pairs of reviewers met to discuss conflicts. Data quality was assessed using the Cochrane Collaboration's Risk of Bias Tool, the Joanna Briggs Critical Appraisal Tool, and the Critical Appraisal Skills Programme Checklist. Thirteen articles were included in the review. None of the articles assessed self-esteem specifically; however, each article assessed aspects of self-esteem (self-concept, self-efficacy, self-worth, depression, quality of life, general well-being, or physical function). All articles reported improvements in the selected outcome measures compared with baseline; two studies that compared two different physical therapy interventions found no significant differences between the interventions. To our knowledge, there is no literature explicitly evaluating self-esteem in postpartum women following physical therapy intervention for lumbopelvic dysfunction. Low self-esteem is shown to predict depression and anxiety; therefore, interventions that increase self-esteem may be useful in reducing the risk of depression.Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Societe des obstetriciens et gynecologues du Canada.

Croisier, E., et al. (2021). "The Efficacy of Dietary Fiber in Managing Gastrointestinal Toxicity Symptoms in Patients with Gynecologic Cancers undergoing Pelvic Radiotherapy: A Systematic Review." Journal of the Academy of Nutrition and Dietetics 121(2): 261.
	Background: Pelvic radiotherapy is a common part of treatment used in gynecologic malignancies. The side effects associated with treatment, such as gastrointestinal toxicity, can be acute and chronic. Previous studies have provided little clarity in regard to the best dietary intervention for management of symptoms.; Objective: The aim of this systematic review was to summarize the evidence on the efficacy of nutrition interventions involving fiber modification in patients with gynecologic cancers undergoing pelvic radiotherapy to prevent or alleviate gastrointestinal side effects, in comparison to standard care, placebo, or no intervention.; Methods: Studies, inclusive of any language and date, up to December 1, 2019, were selected from eight electronic databases: PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, Scopus, Science direct, Clinical Key, Web of Science, and Cochrane. Key study outcomes included gastrointestinal toxicity such as diarrhea/bowel changes, abdominal pain or bloating, and nausea; nutritional status; and quality of life. All studies underwent a quality appraisal using the Academy of Nutrition and Dietetics Quality Criteria Checklist and certainty of evidence was assessed via the Grading of Recommendations Assessment, Development, and Evaluation criteria.; Results: Four studies were included (total number of participants = 89), with quality ratings of neutral or negative. Due to the risk of bias, inconsistency, indirectness, and imprecision, there was very low certainty of evidence that dietary fiber modifications improved these outcomes. Some positive trends regarding improvements in incidence and severity of diarrhea and bowel symptoms were reported; however, the body of evidence was insufficient to form specific recommendations for clinical practice. This is reflected in the Grading of Recommendations Assessment, Development, and Evaluation criteria rating (very low level of certainty) for quality of life and gastrointestinal toxicity outcomes.; Conclusions: This systematic review suggests that supplementary fiber modification during radiation therapy may have some potential benefits with improving gastrointestinal symptoms; however, more definitive evidence and further exploration of fiber in a therapeutic role is required to inform dietary practice. (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Crosby David, A., et al. (2022). "Mid-luteal uterine artery Doppler indices in the prediction of pregnancy outcome in nulliparous women undergoing assisted reproduction." Human fertility (Cambridge, England) 25(4): 670-676.
	Traditionally, the assessment of endometrial receptivity at transvaginal ultrasound scan has been based on the thickness and the morphological appearance of the endometrium. The objective of this study was to prospectively evaluate endometrial thickness (ET), endometrial morphology and uterine artery Doppler parameters prior to assisted reproduction treatment (ART) in the prediction of pregnancy outcome. This was a prospective cohort study. ET, morphology and uterine artery Doppler (UtAD) pulsatility index (PI) and resistance index (RI) were measured in the mid-luteal stage of the menstrual cycle ultrasonographically, timed with urinary luteinizing hormone testing. A total of 50 women were included in the analysis. The clinical pregnancy rate (CPR) per embryo transfer was 42.0% ( n = 21/50). Twenty nine women (58.0%) had an unsuccessful outcome. There were no differences in mean ± SD endometrial thickness (ET) (10.0 ± 1.8 mm vs. 10.5 ± 2.4; p = 0.43), or endometrial morphology (100% ( n = 21) vs 100% ( n = 29); p = 1.00) between the pregnant and not pregnant groups. Similarly, there were no differences in mean ± SD UtAD PI (2.17 ± 0.83 vs. 2.07 ± 0.81; p = 0.67 or mean ± SD UtAD RI (0.84 ± 0.10 vs. 0.81 ± 0.10; p = 0.30). Ultrasonographic endometrial assessment did not differentiate between those who would have a subsequent clinical pregnancy.

Cross, D., et al. (2023). "Does a Kegel Exercise Program Prior to Resistance Training Reduce the Risk of Stress Urinary Incontinence?" International Journal of Environmental Research and Public Health 20(2): 1481.
	This comparative pre-post intervention study investigated the feasibility and benefits of Kegel exercises amongst incontinent women, prior to commencing resistance training (RT), to reduce the risk of stress urinary incontinence (SUI) compared to a group of women without prior Kegel exercises (KE). Incontinence severity index (ISI) score, pelvic floor muscle strength (PFMS), and body composition (such as body mass index (BMI), fat, and muscle mass), were obtained pre and post intervention. Results demonstrated that RT reduced SUI to a significantly greater extent only if preceded by KE as was observed in the Kegel exercise plus RT group (KE + RT) over time. The improvements in total ISI in both the KE + RT and RT groups were large (d = 1.50 and d = 1.17 respectively). A two-way ANOVA indicated a statistically significant improvement in average PFMS within the KE + RT group over time and between the two groups. A positive correlation was found between the average strength of pelvic floor muscles and SUI. Participants in KE + RT group demonstrated a significant increase in muscle mass (p <= 0.001) and concomitant reduction in fat mass (p = 0.018). This study determined a dedicated program of KE preceding a RT program improved average pelvic floor muscle strength and was effective in reducing SUI among incontinent women.Copyright © 2023 by the authors.

Crouthamel, B., et al. (2022). "Effect of Paracervical Block Volume on Pain Control for Dilation and Aspiration: A Randomized Controlled Trial." Obstetrics and Gynecology 140(2): 234-242.
	Objective: To compare pain scores during office dilation and aspiration between low-volume and high-volume paracervical block of the same dose.; Methods: We conducted a multi-site, randomized, single-blind, placebo-controlled trial from October 2018 to December 2020. We randomized participants presenting for office dilation and aspiration under minimal sedation stratified by procedural indication (induced abortion vs early pregnancy loss) to a 20-mL buffered 1% lidocaine paracervical block or a 40-mL buffered 0.5% lidocaine paracervical block, both with two units of vasopressin in a standardized technique. To detect a 15-mm or greater difference in pain at the time of cervical dilation with 80% power and a two-sided alpha of 0.05, a total of 104 participants was required. The study was also powered to detect a 20-mm or greater difference in pain at the time of cervical dilation within each stratum (induced abortion and early pregnancy loss). The primary outcome was pain with cervical dilation on a 100-mm visual analog scale in the overall cohort. Secondary outcomes included pain with cervical dilation within each stratum. We used a Wilcoxon rank-sum test to compare median pain scores between groups.; Results: We enrolled 114 participants. There was no difference in median pain scores between low-volume and high-volume groups during dilation (62 mm vs 59 mm, P=.94), aspiration (69.5 mm vs 70 mm, P=.47), postprocedure (25 mm vs 25 mm, P=.76), or overall (60 mm vs 60 mm, P=.23). Stratified by indication, there were no significant differences in scores at any time point between the low-volume and high-volume paracervical block groups. There was decreased overall pain in patients with induced abortion who received the higher volume paracervical block, though this did not reach statistical significance (67.5 mm vs 60.5 mm, P=.08). Pain during paracervical block administration was similar between groups (55 mm vs 45 mm, P=.24) and there was no difference in occurrence of side effects (P=.63).; Conclusion: We found no difference in pain with cervical dilation among participants who received the low-volume compared with high-volume paracervical block when studied alone.; Clinical Trial Registration: ClinicalTrials.gov, NCT03636451.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Crowe, L., et al. (2023). "Assessing the unmet needs of patients with advanced cancer treated by biological and precision therapies: protocol for TARGET, a mixed methods study." BMJ Open 13(5): e066229.
	Introduction: Biological and precision therapies are increasingly used in cancer treatment. Although they may improve survival, they are also associated with various-and unique-adverse effects, which can be long lasting. Little is known about the experiences of people treated with these therapies. Moreover, their supportive care needs have not been fully explored. Consequently, it is unclear whether existing instruments adequately capture the unmet needs of these patients. The TARGET study seeks to address these evidence gaps by exploring the needs of people treated with these therapies with the aim of developing an unmet needs assessment instrument for patients on biological and precision therapies.; Methods and Analysis: The TARGET study will adopt a multi-methods design involving four Workstreams (1) a systematic review to identify, describe and assess existing unmet needs instruments in advanced cancer; (2) qualitative interviews with patients on biological and precision therapies, and their healthcare professionals, to explore experiences and care needs; (3) development and piloting of a new (or adapted) unmet needs questionnaire (based on the findings of Workstream 1 and Workstream 2) designed to capture the supportive care needs of these patients; and finally, (4) a large-scale patient survey using the new (or modified) questionnaire to determine (a) the psychometric properties of the questionnaire, and (b) the prevalence of unmet needs in these patients. Based on the broad activity of biological and precision therapies, the following cancers will be included: breast, lung, ovarian, colorectal, renal and malignant melanoma.; Ethics and Dissemination: This study was approved by National Health Service (NHS) Heath Research Authority Northeast Tyne and Wear South Research Ethics Committee (REC ref: 21/NE/0028). Dissemination of the research findings will take several formats to reach different audiences, including patients, healthcare professionals and researchers. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Csupor, D., et al. (2019). "Vitex agnus-castus in premenstrual syndrome: A meta-analysis of double-blind randomised controlled trials." Complementary Therapies in Medicine 47: 102190.
	Although chasteberry (Vitex agnus-castus, VAC) has been studied in several clinical trials and available as medicine for the alleviation of premenstrual syndrome (PMS) symptoms, the efficacy of properly characterised preparations has not been assessed in meta-analyses. The aim of our work was to evaluate the efficacy of VAC in PMS. The meta-analysis was performed following the PRISMA guidelines using the PICOS format, taking into account the CONSORT recommendations. PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched for studies on VAC. The analysis assessed the efficacy of properly characterised products VAC compared to a placebo for the alleviation of PMS symptoms in terms of responder rate, considering the decrease of Total Symptom Score or PMS Diary score. The random effects model was used to calculate summary relative risk (RR) and 95% confidence interval (CI). Only those randomised, double-blind, placebo-controlled trials were included that fulfilled the criteria of the CONSORT recommendations aiming at the proper characterization of herbal products. Out of the 21 clinical trials, three studies (520 females) fulfilled the inclusion criteria, comparing the efficacy of special extracts Ze 440 and BNO 1095 to a placebo for the treatment of PMS. VAC preparations were confirmed to be effective in the reduction of PMS symptoms: women taking VAC were 2.57 (95% CI 1.52-4.35) times more likely to experience a remission in their symptoms compared to those taking the placebo. Although several clinical trials have been carried out with VAC, the majority of the studies cannot be used as evidence for efficacy due to incomplete reporting, especially concerning the description of the used medication. More trials following the CONSORT recommendations are needed to assess the efficacy of VAC extracts. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ctis (2023). "Effect of preventive analgesia by injection of a local anesthetic before vaginal incision for hysterectomy by the vNOTES approach: a randomized double-blind study ANOTES study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Code: SCP1698700,Pharmaceutical Form: ,Other descriptive name: ,Product Code: SCP2092119,Pharmaceutical Form: ,Other descriptive name: CONDITION: hysterectomy,Hysterectomy Therapeutic area: Diseases [C] ‐ Female Urogenital Diseases and Pregnancy Complications [C13] PRIMARY OUTCOME: Main Objective:Determine if the injection of Ropivacaine vs. placebo provides a reduction in postoperative pain at H4 after hysterectomy via vNOTES approach. Primary end point(s):The primary endpoint is pain at H4 using the numerical rating scale (NRS for pain). Pain will be assessed by the post‐operative hospital nurse. Secondary Objective:1.Comparison between the 2 groups of Morphine doses administered in the ICU.,2.Comparison between the 2 groups of the time spent in the ICU before returning to the ward.,3.Comparison between the 2 groups of the maximum pain felt in the hospital room between ICU discharge and H4 (before administration of an analgesic on demand). If the patient is still in the ICU at H4 postop, this measurement will be carried out by the ICU nurse).,4.Comparison between the 2 groups of pain at H6 and H8 (at rest, when coughing and when standing), then in the morning, every day, during the first post‐operative week and at the 6‐week post‐operative visit.,5.Comparison between the 2 groups of analgesic consumption (standardized protocol on request. Appendix 1) during inpatient monitoring, then during the first postoperative week.,6.Comparison between the 2 groups of the conversion rate from day hospitalization to conventional hospitalization.,7.Comparison between the 2 groups of preoperative global quality of life at 6 weeks, 6 months and 1 year.,8.Comparison between the 2 groups of sexual quality of life preoperatively, at 6 months and at 1 year.,9.Comparison between the 2 groups of intraoperative and postoperative morbidity (Clavien‐Dindo classification), at 6 weeks. .,10.Comparison between the 2 groups of the occurrence of neuropathic pain, at 24h J7 and 6 months.,11.Comparison between the 2 groups of the occurrence of bleeding during surgery SECONDARY OUTCOME: Secondary end point(s):1. Morphine doses administered in SSPI (in mg) Secondary end point(s):2. Time spent in the ICU before returning to the ward (in minutes) Secondary end point(s):3. Maximum pain experienced in hospital room between ICU discharge and H4. If this pain gives rise to the administration of an analgesic on demand, the pain assessment will be carried out just INCLUSION CRITERIA: • Adult patients aged 18 to 70 inclusive,• Patient scheduled for vNOTES surgery for total hysterectomy for benign pathology, whether or not associated with an adnexal procedure (unilateral or bilateral salpingectomy or adnexectomy (for cysts smaller than 6 cm)).,• Person having read and understood the information letter and signed the consent form,• Person affiliated to a social security scheme

Ctis (2023). "The iCaD Study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: INFLIXIMAB,Product Code: SUB02681MIG,Pharmaceutical Form: POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION,Other descriptive name: ,Strength: 100mg,Product Name: PREDNISOLONE,Product Code: SUB10018MIG,Pharmaceutical Form: TABLET,Other descriptive name: ,Strength: 25mg,Product Name: METHYLPREDNISOLONE,Product Code: SUB08872MIG,Pharmaceutical Form: SUSPENSION FOR INJECTION,Other descriptive name: ,Strength: 40mg,Product Name: PREDNISOLONE,Product Code: SUB10018MIG,Pharmaceutical Form: TABLET,Other descriptive name: ,Strength: 5mg CONDITION: Immune checkpoint inhibitor related colitis Therapeutic area: Diseases [C] ‐ Neoplasms [C04]‐Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective:The objectives of the study are to compare the efficacy and safety of an anti‐inflammatory regimen consisting of initial infliximab concomitant to corticosteroid to corticosteroid alone for the treatment of severe ICI induced colitis/diarrhoea. Primary end point(s):Time (days) to persistent modified CTCAE (mCTCAE; definition according to Table 3) grade = 1 ir‐colitis/diarrhoea. Persistent is defined as grade = 1 ir‐colitis/diarrhoea for five consecutive days or more with no increase in corticosteroid intake, and the event will be calculated from the first day of grade = 1 ir‐colitis/diarrhoea of that period (time frame: seven weeks) Secondary Objective: INCLUSION CRITERIA: Untreated mCTCAE grade 2‐4 diarrhoea or colitis, or persistent mCTCAE grade 2 diarrhoea after administration of loperamide or equivalent for mCTCAE grade = 2 diarrhoea,Usage of prednisolone = 10 mg daily for non irAE is allowed,Diagnostic work up including screening for viral hepatic infection and QuantiFERON‐TB for mycobacterium tuberculosis must be requisitioned but will not need to be reported prior to study enrolment,Women of child bearing potential must have a negative serum (preferred) or urine pregnancy test within 72 hours prior to registration. Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, lo SECONDARY OUTCOME: Secondary end point(s):Cumulative corticosteroid exposure (time frame: seven weeks) Secondary end point(s):Overall Survival stratified by cancer type (time frame: the duration of time from start of randomisation to time of death or up to 24 months) Secondary end point(s):Progression Free Survival stratified by cancer type (time frame: duration of time from start of randomisation to time of progression or death, whichever occurs first or up to 24 months) Secondary end point(s):Proportion of study subjects requiring rescue immunosuppressive medication; Arm A (initial corticosteroid only): infliximab if no improvement to grade = 2 ir‐colitis/diarrhoea after 3 days (time frame: seven weeks); Arm B (initial infliximab): second dose infliximab according to physicians decision if no improvement to grade = 2 ir‐colitis/diarrhoea after seven days Secondary end point(s):Proportion of study subjects with a corticosteroid‐free clinical remission (grade = 1 ir‐colitis/diarrhoea) after seven weeks (time frame: seven weeks) Secondary end point(s):Proportion of study subjects with colectomy or colitis‐specific mortality (time frame: seven weeks) Secondary end point(s):Proportion of study subjects with grade = 1 ir‐colitis/diarrhoea at 72 hours (time frame: 72 hours) Secondary end point(s):Proportion of study subjects with persistent grade = 1 ir‐colitis/diarrhoea at three weeks. Persistent is defined as grade = 1 ir‐colitis/diarrhoea for five consecutive days or more, and the event will be calculated from the first day of grade = 1 ir‐colitis/diarrhoea of that period (time frame: three weeks) Secondary end point(s) roportion of study subjects with recurrence of ir‐colitis/diarrhoea on subsequent reintroduction of ICI Secondary end point(s):Proportion of study subjects with treatment related adverse events as assessed by CTCAE v5.0 (time frame: 12 weeks) Secondary end point(s):QoL by means of EORTC‐QLQ‐C30 questionnaire and selected PRO‐CTCAE items at baseline, 3, 12, 24, and 52 weeks after randomisation (time frame: 52 weeks) Secondary end point(s):Subgroup analyses stratified for ipilimumab containing ICI for time (days) to persistent grade = 1 ir‐colitis/diarrhoea. Persistent is defined as grade = 1 ir‐colitis/diarrhoea for five consecutive days or more, and the event will be calculated from the first day of grade = 1 ir‐colitis/diarrhoea of that period (time frame: seven weeks) Secondary end point(s):Translational research projects to explore the diversity and evolution of the immunologic cells and faecal microbiome from initiation of immune checkpoint inhibition, to the event of ir‐colitis/diarrhoea, and to resolution after immunosuppressive therapy

Ctri (2021). "Comparison of epidural catheter fixation methods." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention1: Lockit fixator device: The epidural catheter will be threaded through the central eyelet of Lockit fixator device, after its exit from skin. The adhesive on the Lockit device sticks on the skin and the clamp is closed over the catheter. Intervention2: Subcutaneous tunneling: The epidural catheter will be subcutaneously tunneled vertically using a Tuohy 18G epidural needle 1.5 cm lateral to the midline. The epidural needle will be used to create the tunnel 3‐4 cm long in subcutaneous plane, moving from above downward after local infiltration, with its lower end at the same horizontal level as the epidural puncture site. A small loop of catheter will be left between the epidural puncture site and the tunnel entry. A piece of sterile gauze will be placed under this loop. The catheter is gently pulled up to the right shoulder, and the entire length will be covered by Tegaderm. Control Intervention1: Standard dressing: coiled catheter at skin exit under a transparent adhesive dressing CONDITION: Health Condition 1: K319‐ Disease of stomach and duodenum, unspecified Health Condition 2: C189‐ Malignant neoplasm of colon, unspecified Health Condition 3: C649‐ Malignant neoplasm of unspecifiedkidney, except renal pelvis Health Condition 4: C55‐ Malignant neoplasm of uterus, partunspecified Health Condition 5: V099‐ Pedestrian injured in unspecifiedtransport accident Health Condition 6: S729‐ Unspecified fracture of femur Health Condition 7: S829‐ Unspecified fracture of lower leg PRIMARY OUTCOME: To identify a simple, safe and effective method of fixing the epidural catheter.Timepoint: During fixation ; At end of surgery during shifting ; During removal ‐ at 24hrs SECONDARY OUTCOME: Patient comfortTimepoint: During catheter placement INCLUSION CRITERIA: Patients requiring post operative epidural analgesia

Ctri (2021). "Effect of Lidocaine Infusion on Post Operative Pain Relief and Recovery After Major Abdominal Cancer Surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention1: LIDOCAINE INFUSION: AFTER GA, IV LIDOCAINE INFUSION WILL BE STARTED AT THE RATE OF 1.5MG/KG BOLUS OVER 10 MIN, FOLLOWED BY 1 MG/KG/HR TILL END OF SURGERY Control Intervention1: PLACEBO CONTROLL WITH NORMAL SALINE: EQUAL VOLUME OF NORMAL SALINE WILL BE INFUSED OVER 10 MINS AND TILL THE END OF SURGERY CONDITION: Health Condition 1: C19‐ Malignant neoplasm of rectosigmoidjunction Health Condition 2: C689‐ Malignant neoplasm of urinary organ, unspecified Health Condition 3: C55‐ Malignant neoplasm of uterus, partunspecified PRIMARY OUTCOME: TOTAL OPIOID CONSUMPTION, NUMERICAL RATING SCALE FOR PAIN,TIME TO RESCUE ANALGESIA, RECOVERY PROFILETimepoint: T1‐END OF SURGERY, T2‐T7‐2,4,6,8,12,24 HR POST SURGERY SECONDARY OUTCOME: TIME TO RETURN OF GI FUNATION, TIME OF ICU DISCHARGE, LA TOXICITY, INCIDENCE OF CHRONIC PAIN AT 3 MONTHSTimepoint: T1‐END OF SURGERY, T2‐T7‐2,4,6,8,12,24 HR POST SURGERY,T8‐3 MONTHS POST SURGERY INCLUSION CRITERIA: all adult female patients undergoing major abdominal oncosurgeries

Ctri (2021). "INTERNATIONAL VALIDATION STUDY OF SENTINEL NODE BIOPSY IN EARLY CERVICAL CANCER." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention1: SLN dissection only: A full lymphadenectomy will not be performed. The radical hysterectomy or trachelectomy will be done Control Intervention1: SLN and PLN dissection: A full lymphadenectomy will be performed. The radical hysterectomy or trachelectomy will be done CONDITION: Health Condition 1: C539‐ Malignant neoplasm of cervix uteri, unspecified Health Condition 2: C00‐D49‐ Neoplasms PRIMARY OUTCOME: DFS defined as the time interval between randomization and recurrence ; (local/distant) or second cancer or death (all causes) ; HR‐QoL of patients assessed with EORTC QLQC 30 and QLQ‐CX24 with 3 ; targeted dimensions: pain, global health score and physical functioning ; scores at 3 years.Timepoint: 3 years SECONDARY OUTCOME: Outcome of pN1 patients according to the size of metastasis and treatment; ; Evaluation of mapping with ; indocyanine green (ICG); ; Surgical morbidity and mortality; ; Other dimensions of HR‐QoL; ; Positive and negative predictive ; values of SLN biopsy; ; Overall survival (OS); ; Recurrence free survival (RFS); ; A cost analysis will be performed; ; Lymphatic and lower limb ; complications ; ; Timepoint: At 3 years INCLUSION CRITERIA: 1. Patient must be â?¥ 18 years old. 2. With squamous or adenocarcinoma of the cervix (proven by biopsy or cone biopsy) 3. Stage Ia1 with lymphovascular emboli, Ia2, Ib1, Ib2 and IIa1, (clinical stage) of the 2018 FIGO classification. 4. Maximum diameter â?¤ 40 mm by clinical examination and/or magnetic resonance imaging (MRI) 5. No suspicious on pelvic MRI with an exploration up to the left renal vein 6. ECOG performance status 0‐2 7. Signed informed consent and ability to comply with follow‐up

Cuccia, F., et al. (2023). "The Role of Radiotherapy in the Management of Vaginal Melanoma: A Literature Review with a Focus on the Potential Synergistic Role of Immunotherapy." Journal of Personalized Medicine 13(7).
	Among the mucosal melanomas, vaginal melanomas are very rare tumors, accounting for less than 20% of melanomas arising from the female genital tract. They occur most frequently in women in post-menopausal age, but younger patients may also experience this neoplasm, mainly located in the lower third of the vagina or the anterior wall. The optimal management of this tumor remains controversial, with surgery reported as the most frequently adopted approach. However, a clear benefit of surgical treatment in terms of survival has not yet been demonstrated. Conversely, radiotherapy may represent an attractive non-invasive alternative, and there are several favorable reports of the role of radiation therapy, either delivered with photons, brachytherapy, or hadrontherapy. A wide range of techniques and fractionation regimens are reported with substantially good tolerance to the treatment, and acute G3 or higher toxicities are reported only in the case of concurrent immunotherapy. Of note, due to the rarity of the disease, there is a lack of high-level evidence for the optimal therapeutic option. In this scenario, recent studies theorize the possibility of developing combinatorial approaches of radiotherapy with immunotherapy based on cutaneous melanomas reports. In this review, we aim to summarize the evidence available in the literature supporting the role of definitive radiotherapy for vaginal melanomas, with a focus on the combination of RT with immunotherapy, in terms of optimal timing and biological rationale.

Cui, Q., et al. (2024). "Systematic analysis of perivascular epithelioid cell neoplasms in the female reproductive tract: a comprehensive review." Future oncology (London, England) 20(5): 283-295.
	Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports exist on gynecological PEComa, primarily treated with surgery; adjuvant therapy is considered in high-risk cases. This systematic review aims to summarize the origin and clinical, pathological and molecular characteristics of uterine PEComa, focusing on treatment options for gynecological PEComa. A comprehensive PubMed review of gynecological PEComa reports was conducted. A detailed examination of the literature ensured a thorough understanding. Gynecological PEComa diagnosis relies on histology and immunology. Despite therapy controversies, surgery remains the mainstay. Adjuvant therapy efficacy in high-risk cases is uncertain. mTOR inhibitors are the first line; alternative treatments, including angiogenesis and aromatase inhibitors, should be considered.

Cui, Y., et al. (2022). "Does electroacupuncture benefit mixed urinary incontinence? A systematic review and meta-analysis with trial sequential analysis." International Urogynecology Journal 33(4): 751-766.
	Introductin and hypothesis: Mixed urinary incontinence (MUI) comprises a combination of urgency and stress. The efficacy and safety of electroacupuncture (EA) for the treatment of MUI remain unclear. Objective(s): To assess the efficacy and safety of EA in treating MUI. Method(s): We searched PubMed, CENTRAL, Embase, Web of Science, four Chinese databases, clinical research registration platforms, grey literature, and the reference lists of the selected studies. Risk of bias and quality were evaluated using the Revman 5.4 and Jadad scores. Meta-analysis was performed using Stata 15.1 software. Trial sequential analysis (TSA) was used to assess the stability of the results. Result(s): Eight randomized controlled trials comprising 847 patients were included. The meta-analysis results showed that compared with antimuscarinic drugs plus pelvic floor muscle training, EA resulted in significantly less pad weight on the 1-h pad test and statistically significantly lower severity scores on the International Consultation on Incontinence Questionnaire Short Form. The change in the 72-h incontinence episode frequency difference was not statistically significant, and there was no outcome of overall response rate and quality of life in this meta-analysis. Few adverse events occurred in the EA group. The TSA results suggested that the result of change from baseline in the 1-h pad test was stable and the evidence was conclusive. Conclusion(s): EA could be a potential treatment option for MUI and is relatively safe. Nevertheless, because of the limitations of this study, our conclusions should be interpreted with caution, and further studies are needed to confirm the comprehensive clinical efficacy and placebo effect of EA.Copyright © 2021, The Author(s).

Cuijpers, P. and E. Karyotaki (2021). "The effects of psychological treatment of perinatal depression: an overview." Archives of Women's Mental Health 24(5): 801-806.
	Perinatal depression is an important public health problem. Psychological interventions play an essential role in the treatment of depression. In the current paper, we will present the results of a series of meta-analyses on psychological treatments of perinatal depression. We report the results of a series of meta-analyses on psychological treatments of depression, including perinatal depression. The meta-analyses are based on a database of randomized trials on psychotherapies for depression that has been systematically developed and updated every year. Psychological interventions are effective in the treatment of perinatal depression with a moderate effect size of g = 0.67, corresponding with a NNT of about 4. These effects were still significant at 12 months after the start of the treatment. These interventions also have significant effects on social support, anxiety, functional impairment, parental stress, and marital stress. Possibly the effects are overestimated because of the use of waiting list control groups, the low quality of the majority of trials and publication bias. Research on psychotherapies for depression in general has shown that there are no significant differences between the major types of therapy, except for non-directive counseling that may have somewhat smaller effects. CBT can also be delivered in individual, group, telephone, and guided self-help format. Interventions in subthreshold depression are also effective and may prevent the onset of a full-blown depressive disorder, while therapies may be less effective in chronic depression. Psychological interventions are effective and deserve their place as first-line treatment of perinatal depression.Copyright © 2021, The Author(s).

Culpin, I., et al. (2023). "Maternal postnatal depressive symptoms and offspring emotional and behavioral development at age 7 years in a U.K. birth cohort: The role of paternal involvement." Developmental psychology 59(4): 770-785.
	There is considerable variability in developmental outcomes of children whose mothers experience depression. Few longitudinal studies have examined contributions of paternal involvement in the association between maternal postnatal depression (PND) and offspring development. We examined pathways from maternal PND at 8 weeks (Edinburgh Postnatal Depression Scale; total score) to offspring emotional and behavioral development at 7 years (Strengths and Difficulties Questionnaire; total score) through behavioral, affective, and cognitive dimensions of paternal involvement in a U.K.-based birth cohort (Avon Longitudinal Study of Parents and Children; n = 3,434). Analyses were adjusted for baseline confounders and paternal PND (Edinburgh Postnatal Depression Scale; total score) as an intermediate confounder. Maternal PND was strongly associated with offspring development, but this association was not mediated by the combination of all indirect pathways through various dimensions of paternal involvement. Only father-child conflict emerged as a risk factor for adverse offspring development and as a mediator in the association between maternal PND and offspring development (albeit the effect size was small). If found causal, interventions that reduce father-child conflict may reduce the risk of adverse development in offspring of mothers with PND. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cunningham Jasmyn, E. A., et al. (2021). "Sleep, biological rhythms and anxiety in the perinatal period: a systematic review protocol." BMJ Open 11(8): e046767.
	Introduction: Pregnancy and new parenthood is an exciting time, but also a stressful life event that can predispose to mental health challenges. Perinatal anxiety is one such challenge, and is an important contributor to parental distress and other negative outcomes. Sleep and biological rhythms are often disrupted in the perinatal period. These disruptions have been associated with postpartum depression, and in some cases with perinatal anxiety. However, the literature concerning the association with perinatal anxiety is inconsistent and may be methodologically limited. To our knowledge, there has been no comprehensive review published characterising the relationships between sleep, biological rhythms, and perinatal anxiety and related disorders to date. In this systematic review, we will summarise the current state of the literature concerning these relationships, allowing us to highlight gaps and potentially inform clinical understanding of perinatal anxiety, sleep and biological rhythms.; Methods and Analysis: Primary research articles will be eligible for inclusion if they assess perinatal anxiety or related disorders using validated criteria (self-report or diagnostic), assess sleep and biological rhythms in the perinatal period, include >4 participants and meet other inclusion/exclusion criteria. We will conduct comprehensive searches of MEDLINE, PsycINFO, Embase and CINAHL, with coverage spanning from database conception to search date (August 1, 2021). Key search concepts include (1) the perinatal period, (2) sleep/biological rhythms and (3) anxiety. Risk of bias will be evaluated using the Cochrane Risk of Bias Tool. Data will be narratively synthesised, with quantitative synthesis included if possible. When relevant, strength of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation criteria, and potential publication bias will be assessed.; Ethics and Dissemination: Research ethics approval is not required. Study results will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results will be disseminated to relevant stakeholders as conference presentation(s) and submitted for publication in a peer-reviewed journal.; Prospero Registration Number: 200166.; Competing Interests: Competing interests: AS has received research funding from Pfizer. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Curillo-Aguirre, C. A. and E. Gea-Izquierdo (2023). "Effectiveness of Pelvic Floor Muscle Training on Quality of Life in Women with Urinary Incontinence: A Systematic Review and Meta-Analysis." Medicina (Kaunas, Lithuania) 59(6).
	Background and Objectives: Urinary incontinence (UI) is a condition that is more common in women than men and has an increasing prevalence with age. It provides a range of psychological and physical burdens that negatively affect the patient's quality of life (QoL). However, the economic burden for the healthcare system is being augmented due to the increasing life expectancy of the population. This article aims to identify the effectiveness of pelvic floor muscle training (PFMT) on the QoL in women with UI. Material(s) and Method(s): A systematic review and meta-analysis were conducted in the PubMed, EMBASE, ProQuest medicine, Cochrane Library, and Google Scholar databases. The terms selected according to components of PICOS were women with urinary incontinence, pelvic floor muscle training, watchful or other types of therapies, quality of life, randomized controlled trials, and interventional or observational studies. The articles included were those published between November 2018 and November 2022. Ten articles were found for the systematic review and eight for the meta-analysis. Result(s): The QoL moderately increased when PFMT was used on women with UI, the results indicating an overall small effect on the QoL across the controlled studies and a moderate effect on the QoL across the one-group pre-post-studies. Conclusion(s): Specific QoL domains, such as social activities and general health, also demonstrated benefits from PFMT interventions. This study confirmed the effectiveness of PFMT on the QoL in women with UI, mainly for patients with stress urinary incontinence.

Curlin, H. L. and T. L. Anderson (2022). "Endometrial Cryoablation for the Treatment of Heavy Menstrual Bleeding: 36-Month Outcomes from the CLARITY Study." International Journal of Women's Health 14: 1083-1092.
	Study Objective: To examine long-term outcomes from the pivotal study that evaluated the safety and effectiveness of the Cerene Cryotherapy Device (Channel Medsystems, Berkeley, CA) in premenopausal women with heavy menstrual bleeding due to benign causes who have completed childbearing. Method(s): The prospective, multicenter, single-arm, open-label study had eight sites in the USA, one in Mexico, and two in Canada. Inclusion criteria included uterine sound <=10 cm, endometrial cavity length 2.5 to 6.5 cm, age 25 to 50 years, a pictorial blood loss assessment chart score of >=150, no submucosal myomata and/or uterine obstruction, distortion, or abnormality. A total of 242 subjects underwent a 2.5-minute cryoablation. Long-term follow-up visits were conducted at Month 24 and Month 36. Data collected included gynecological adverse events, description of last menstrual period, contraception status, self-report of pregnancy, medical or surgical interventions to treat abnormal uterine bleeding, satisfaction, recommendation, and quality of life (QoL). QoL outcomes were measured with the Menorrhagia Impact Questionnaire (MIQ) and the Premenstrual Symptoms Impact Survey (PMSISTM). Result(s): 201 subjects completed their Month 36 final study visit. Subject outcomes were comparable to those at Month 12. Eighty-nine percent of subjects reported amenorrhea, a lighter-than-normal, or normal period, 91% of subjects had no or slight limitations in MIQ measured activities, and 85% reported premenstrual symptoms at a low frequency. Eighty-five percent of the subjects were satisfied or very satisfied. The cumulative incidence of hysterectomy was 5% and reintervention was 8.7%. Forty-nine gynecologic adverse events (AE) were reported; one non-serious AE, postcoital bleeding, was reported as related to the procedure. No serious device-related or procedure-related AEs were reported. Conclusion(s): Study data demonstrate that the positive effects of Cerene Cryotherapy Device treatment are sustained through Month 36 and that the risks associated with the device and procedure are low (ClinicalTrials.gov; NCT02842736).Copyright © 2022 Curlin and Anderson. All rights reserved.

Currie Cheryl, L., et al. (2020). "The impact of eHealth group interventions on the mental, behavioral, and physical health of adults: a systematic review protocol." Systematic Reviews 9(1): 217.
	Background: COVID-19 has resulted in an increased demand for eHealth services globally. There is emerging evidence for the efficacy for group eHealth interventions that support population-based mental health and wellbeing, but a systematic review is lacking. The primary objective of this systematic review is to summarize the evidence for eHealth group counseling and coaching programs for adults. A second objective is to assess, within studies selected for our primary objective, the impact of programs that encourage PA on outcomes compared to those that do not.; Methods: Randomized controlled trials that assess the impact of eHealth group counseling or coaching programs on mental health, health behavior, or physical health activity among community-dwelling adults will be included. We will search the following electronic databases (from January 2005 onwards): MEDLINE, PsycINFO, CINHAL, and the Central Register of Controlled Trials. The primary outcomes will be changes in mental health conditions (e.g., depression, anxiety, stress, quality of life), behavioral health conditions (e.g., substance use, smoking, sexual behavior, eating behavior, medication adherence), and physical health conditions (e.g., coping with cancer, menopausal symptoms, arthritis pain). Secondary outcomes will be changes in physical activity. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion with a third reviewer. A narrative synthesis without meta-analysis will be conducted. The strength of the body of evidence will be assessed using GRADE. The risk of bias in individual studies will be appraised using the Cochrane Risk of Bias 2.0 tool. Potential sources of gender bias in included studies will be considered at all stages of the planned review.; Discussion: This review will contribute to the literature by providing evidence on the effectiveness of eHealth counseling and coaching programs delivered to adults in a group format.; Systematic Review Registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42020187551 ).

Cutting, H., et al. (2023). "Baseline Characteristics of Participants in a Multicenter Randomized Clinical Trial of Vestibulodynia: Understanding Pathophysiology and Determining Appropriate Treatments (Vestibulodynia: UPDATe) . Show more." Journal of Sexual Medicine 20(Supplement 2).
	Introduction Vestibulodynia (VBD) is a common cause of sexual pain that affects ~14 million women in the United States. Many different therapies are used on a trial-and-error basis which can delay effective care. Two distinct VBD subtypes may benefit from different types of treatment: 1) VBD peripheral (VBD-p) - pain localized to the vulvar vestibule and 2) VBD central (VBD-c) - VBD and >1 chronic overlapping pain condition(s) affecting remote body regions. Thus, we are evaluating the efficacy of peripheral, central, and combined treatments for VBD-p vs VBD-c. We will also evaluate cytokine and microRNA biomarkers to help determine pathophysiology and predict treatment response. Objective To describe the design and present baseline participant characteristics of our ongoing RCT for VBD. Methods This is a multi-site randomized, double-blind trial that will enroll participants to one of four parallel arms: 1) peripheral treatment with 5% lidocaine/0.5 mg/ml 0.02% estradiol compound cream and placebo pills, 2) central treatment with tricyclic antidepressant nortriptyline pills and placebo cream, 3) lidocaine/estrogen cream and nortriptyline pills, or 4) placebo cream and placebo pills. The treatment phase will last 16 weeks, with clinical outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). We will enroll 400 women 18-50 years who report tenderness at the vulvar vestibule and report >3/10 pain with tampon insertion on a numeric rating scale (NRS). Primary outcome is pain with tampon test. Secondary outcomes include self-reported pain on the McGill Pain Questionnaire, psychosocial measures, pressure pain thresholds (PPTs) measured at the vaginal vestibule, levator ani muscles, and remote body sites, and levels of cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing to determine the ability of these biomarkers to predict treatment response. Results So far 135 subjects have enrolled and 78 of these have completed the study. Enrollment remains open, with 27 subjects active and 30 subjects discontinued. Mean (range) age is 26.9 (18-48) years and body mass index is 23.7 (16-37). Self-disclosed racial identity of subjects is: White (67.4%), Asian (14.1%), Multiracial (9.6%), Black (8.9%), with 14.8% of subjects identifying as Hispanic or Latino. Of the enrolled subjects, 94/135 (69.6%) subjects are categorized VBD-c, and 41/135 (30.4%) are categorized VBD-p. Of those categorized as VBD-c, fibromyalgia syndrome (39.3%), endometriosis (34.1%), back pain (25.20%), irritable bowel syndrome (19.3%), chronic headaches (16.3%), temporomandibular disorder (11.1%), interstitial cystitis (10.4%) and chronic fatigue syndrome (1.5%) have been reported. At baseline visit, subjects report an average tampon test score of 4.2 (2.11) and 93.3% of subjects report pain during vaginal intercourse. Conclusions We have launched a multicenter randomized trial to evaluate the efficacy of peripherally and centrally acting medications used for treating unique VBD subtypes based on distinct clinical and biological signatures. We hope to advance our knowledge of the pathophysiologic mechanisms underlying VBD-p and VBD-c, determine the efficacy of peripheral, central, and combined therapies in alleviating pain in women with VBD-p and VBD-c, and identify biomarkers that predict treatment response.

Cyr, M. P., et al. (2022). "Changes in pelvic floor morphometry and muscle function after multimodal physiotherapy for gynaecological cancer survivors suffering from dyspareunia: a prospective interventional study." Physiotherapy (United Kingdom) 114: 54-62.
	Objective: To investigate the changes in pelvic floor morphometry and muscle function after multimodal pelvic floor physiotherapy treatment in gynaecological cancer survivors suffering from painful intercourse (dyspareunia). Design(s): Prospective interventional study. Setting(s): Three university hospitals. Participant(s): Thirty-one gynaecological cancer survivors with dyspareunia. Intervention(s): The treatment consisted of 12 weekly sessions of physiotherapy combining education, pelvic floor muscle exercises with biofeedback, manual therapy and home exercises. Main Outcome Measure(s): Women were assessed at baseline and post-treatment. Pelvic floor morphometry was evaluated at rest and on maximal contraction by measuring bladder neck position, anorectal and levator plate angles as well as levator hiatal dimensions with three-dimensional/four-dimensional transperineal ultrasound imaging. Pelvic floor muscle function was evaluated by measuring passive forces (muscle tone measure), flexibility, stiffness, strength, coordination and endurance with an intra-vaginal dynamometric speculum. Result(s): Significant changes in pelvic floor morphometry and muscle function were found post-treatment. The parameters assessing the changes from rest to maximal contraction significantly improved (e.g., mean change of levator hiatal area narrowing 14%, 95% CI 11-18, Cohen's d effect size 1.48)), supporting the hypothesis of decreased muscle tone and improved muscle contractility following treatment. Women also presented with a significant decrease in tone (mean change -0.4 N, 95% CI -0.7 to -0.1, Cohen's d effect size 0.57) and stiffness (mean change -0.1 N/mm, 95% CI -0.2 to -0.1, Cohen's d effect size 0.59), as well as significant improvements in flexibility (mean change 9.0 mm, 95% CI 5.8-12.2, Cohen's d effect size 1.08), coordination (mean change 3 rapid contractions, 95% CI 2-4, Cohen's d effect size 0.85) and endurance (mean change 683%*s, 95% CI 388-978, Cohen's d effect size 0.90). Conclusion(s): Our findings suggest significant improvements in pelvic floor morphometry and muscle function after a multimodal physiotherapy treatment in gynaecological cancer survivors with dyspareunia. These effects may represent key treatment mechanisms to reduce dyspareunia, supporting the rationale for multimodal physiotherapy in this population. Clinical trial registration number (ClinicalTrials.gov): NCT03935698.Copyright © 2021 Chartered Society of Physiotherapy

Czakert, J., et al. (2022). "Plant Fragrances Are Like Music for Our Senses: A Scoping Review of Aromatherapy in Gynecologic Cancers and Breast Cancer Care." Journal of Integrative and Complementary Medicine 28(5): 377-390.
	Introduction: Essential oil (EO) applications via inhalation and/or absorption through the skin-often referred to as aromatherapy-have particular relevance as complementary to cancer treatment and follow-up care. Aromatherapy is of particular interest for controlling symptoms and enhancing the general well-being of people with cancer. This is indicated by the increasing number of empirical studies on this topic. Although numerous reviews have summarized the extensive primary research about aromatherapy and cancer, no review on aromatherapy use targeting women with gynecologic and breast cancers currently exists. Our scoping review aims at giving an overview of the state of research about aromatherapy in this specific target group. By summarizing and describing study characteristics, based on methodological decisions and content, we intend to offer implications for future research, focused on the use of EO in women with gynecologic and breast cancers. Methods: A systematic scoping review was conducted, based on the literature, and using the extension of the PRISMA statement for scoping reviews (PRISMA-ScR). The databases PubMed and CINHAHL were searched in a multi-stage, iterative process taking the most relevant terms under consideration, given our research interest and Boolean operators. The included studies were analyzed and summarized through (1) a table matrix including categories of interest and (2) qualitative content analysis. Results: One hundred seventy studies were examined, and 10 were included in this review. They show high heterogeneity in how the term aromatherapy is defined, in content, research design, EO used, application, and outcomes. However, all 10 studies exclusively targeted women with breast cancer in different states of cancer treatment. Conclusions: Challenges of research within this field point to the heterogeneous use and classification of the term aromatherapy, the differentiation of the principle of action of EO, the lack of transparency in how EO are reported and described (e.g., botanical names, company, dosage, mixing ratios), and the need to include subjective perceptions. Ten implications for future research based on these challenges are given.

da Mata Kyannie Risame, U., et al. (2021). "Telehealth in the rehabilitation of female pelvic floor dysfunction: a systematic literature review." International Urogynecology Journal 32(2): 249-259.
	Introduction and Hypothesis: The pandemic caused by coronavirus disease 2019 (COVID-19) increased the awareness and efforts to provide care from distance using information technologies. We reviewed the literature about the practice and effectiveness of the rehabilitation of the female pelvic floor dysfunction via telehealth regarding symptomatology and quality of life and function of pelvic floor muscles (PFM).; Methods: A bibliographic review was carried out in May 2020 in the databases: Embase, Medline/PubMed, LILACS and PEDro. A total of 705 articles were reviewed after the removal of duplicates. The methodological quality of the articles was evaluated by the PEDro scale. Two authors performed data extraction into a standardized spreadsheet.; Results: Four studies were included, two being randomized controlled trials. Among the RCTs, only one compared telehealth with face-to-face treatment; the second one compared telehealth with postal treatment. The other two studies are follow-up and cost analysis reports on telehealth versus postal evaluation. Data showed that women who received the intervention remotely presented significant improvement in their symptoms, such as reducing the number of incontinence episodes and voiding frequency, improving PFM strength and improving quality of life compared to women who had the face-to-face treatment.; Conclusions: Telehealth promoted a significant improvement in urinary symptoms, PFM function and quality of life. Telehealth is still emerging, and more studies are needed to draw more conclusions. The recommendations of the governmental authorities, physical therapy councils and corresponding associations of each country also need to be considered.

da Rocha Rodrigues, A., et al. (2022). "ESTIMULAÇÃO ELÉTRICA NERVOSA TRANSCUTÂNEA E SÍNDROME DA DISMENORREIA PRIMÁRIA: EXISTE RELAÇÃO DO TEMPO DE INTERVENÇÃO COM O ALÍVIO DE DOR?" Revista inspirar movimento & saude 22(4): 1‐18.
	
Dafni, U., et al. (2021). "Efficacy of cancer vaccines in selected gynaecological breast and ovarian cancers: A 20-year systematic review and meta-analysis." European journal of cancer (Oxford, England : 1990) 142: 63-82.
	Background: Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far.; Design: A systematic review and meta-analysis was conducted to evaluate vaccines' efficacy on breast cancer (BC) and ovarian cancer (OC) patients. Our search was based on the PubMed electronic database, from 1st January 2000 to 4th February 2020.; Objective: response rate (ORR) was the primary end-point of interest, while progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Analysis was performed separately for BC and OC patients. Pooled ORRs were estimated by fixed or random effects models, depending on the detected degree of heterogeneity, for all studies with more than five patients. Subgroup analyses by vaccine type and treatment schema as well as sensitivity analyses, were implemented.; Results: Among 315 articles initially identified, 67 were eligible for our meta-analysis (BC: 46, 1698 patients; OC: 32, 426 patients; where both BC/OC in 11). Dendritic-cell and peptide vaccines were found in more studies, 6/10 BC and 10/13 OC studies, respectively. In our primary BC analysis (21 studies; 428 patients), the pooled ORR estimate was 9% (95%CI[5%,13%]). The primary OC analysis (12 studies; 182 patients), yielded pooled ORR estimate of 4% (95%CI[1%,7%]). Similar were the results derived in sensitivity analyses. No statistically significant differences were detected by vaccine type or treatment schema. Median PFS was 2.6 months (95% confidence interval (CI)[1.9,2.9]) and 13.0 months (95%CI[8.5,16.3]) for BC and OC respectively, while corresponding median OS was 24.8 months (95%CI[15.0,46.0]) and 39.0 months (95%CI[31.0,49.0]). In almost all cases, the observed toxicity was only moderate.; Conclusion: Despite their modest results in terms of ORR, therapeutic vaccines in the last 20 years display relatively long survival rates and low toxicity. Since a plethora of different approaches have been tested, a better understanding of the underlying mechanisms is needed in order to further improve vaccine efficacy.; Competing Interests: Conflict of interest statement UD has served as advisor/consultant for Roche. GC has received grants, research support and/or is coinvestigator in clinical trials by BMS, Celgene, Boehringer Ingelheim, Roche, Iovance and Kite; has received honoraria for consultations or presentations by Roche, Genentech, BMS, AstraZeneca, Sanofi-Aventis, Nextcure and GeneosTx; has patents in the domain of antibodies and vaccines targeting the tumour vasculature as well as technologies related to T-cell expansion and engineering for T-cell therapy; and receives royalties from the University of Pennsylvania related to T-cell therapy. KZ has provided consulting or participation in advisory boards of: AstraZeneca, Daiichi, Genomic Health (Exact Science), Lilly, MSD, Mylan, Novartis, Pfizer, Roche; has received travel funding by AstraZeneca, Pfizer, Roche, Pierre Fabre; has unrestricted funding for organisation of scientific events by AstraZeneca, Daiichi, Eisai, Exact Science, Lilly, MSD, Mylan, Novartis, Pfizer, Roche, Synlab; has research funding by Roche. AS has served as advisor/consultant for Roche, AstraZenca, Tesaro-GSK, Celgene-BMS; has received travel/educational/research grants by Roche, AstraZenca-MSD, GSK, Celgene, Agen, BMS, Pfizer, Clovis, Novartis. LK has received grants in clinical trials by BMS, BTG and Nestle.; has received honoraria for consultations GeneosTx. All remaining authors have declared no conflicts of interest. (Copyright © 2020. Published by Elsevier Ltd.)

Daggez, M., et al. (2023). "Prophylactic complex physiotherapy in gynecologic cancer survivors: patient-reported outcomes based on a lymphedema questionnaire." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(12): 1928-1933.
	Objective: Lower extremity lymphedema secondary to cancer treatment impacts quality of life for gynecological cancer survivors. Complex decongestive physiotherapy is applied when lymphedema is diagnosed, but prophylactic physiotherapy is not yet a standard of care. The aim of this study is to evaluate prophylactic complex physiotherapy in patients with gynecological cancer and its effects on patient-reported symptoms based on the Gynecologic Cancer Lymphedema Questionnaire.; Methods: The data of patients diagnosed with gynecological cancers who underwent lymphadenectomy from July 2021 to June 2022 was evaluated. All patients were referred to the physiotherapy unit before adjuvant treatment. Patients who accepted prophylactic physiotherapy were informed and massage and exercise training were implemented, whereas patients who declined were solely informed. Bilateral lower extremity circumferences were measured at 1, 3, 6, and 12 months at the levels of 10 cm, 30 cm, and 50 cm above the heels. A translated form of the Gynecologic Cancer Lymphedema Questionnaire was administered to all patients at the last visit.; Results: A total of 100 patients were included in the study. Patients were diagnosed with endometrial (50%), ovarian (32%), cervical (16%), and vulvar (2%) cancer. Overall, 70% underwent systematic pelvic±para-aortic lymphadenectomy whereas sentinel lymph node mapping was performed in 30%. Lymphedema was seen in 5% (n=3) of the prophylactic physiotherapy positive group and in 60% (n=24) of the physiotherapy negative group. The median score was 3 (range 1-5) in the physiotherapy positive group and 16 (range 9-20) in the physiotherapy negative group. In patients diagnosed with lymphedema in the physiotherapy negative group, systematic lymphadenectomy was performed in 91.7% (n=22) and a higher number of lymph nodes was extracted (median 45.5; p=0.002).; Conclusion: Prophylactic complex physiotherapy is associated with lower rates of lymphedema and better patient-reported symptom scores according to the Gynecologic Cancer Lymphedema Questionnaire.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Dagher, C., et al. (2023). "Molecular subtyping in endometrial cancer: A promising strategy to guide fertility preservation." Gynecologic Oncology 179: 180-187.
	Objectives: To investigate the association of molecular subtype with progesterone response in patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). Method(s): Premenopausal patients aged <=48 years with tumor-normal sequencing data who received progesterone for EC/AEH from 1/1/2010-6/30/2021 were identified. Tumors were classified as POLE-ultramutated, microsatellite instability-high (MSI-H), copy number-high (CN-H), or copy number-low (CN-L) molecular subtype. Best response to progesterone was compared by subtype. Appropriate statistical tests were performed. Result(s): Of 20 patients, 7 (35%) had AEH and 13 (65%) had EC. Sixteen tumors (80%) were CN-L, 3 (15%) were MSI-H, and 1 (5%) was POLE-ultramutated. Median time on progesterone was 22 months (range, 3-115). Ten patients (50%) had complete response (CR); median time to CR was 9 months (range, 3-32). Four patients (20%) had stable disease (SD) and 6 (30%) had progressive disease (PD). For CN-L tumors, 10 patients (62%) had CR, 3 (19%) had SD, and 3 (19%) had PD. For MSI-H tumors, 1 patient (33%) had SD and 2 (66%) had PD. For POLE-ultramutated tumors, 1 patient had PD. Median follow-up was 48 months (range, 12-123). Four of 10 patients (40%) with CR recurred; median time from CR to recurrence was 16 months (range, 5-102). Conclusion(s): Molecular subtype may be associated with progesterone response in patients with EC/AEH. CN-L tumors had the best response, and MSI-H tumors had the poorest. Recurrence after CR is common, and close surveillance is warranted. Larger studies investigating the role of molecular classification in medical management of EC/AEH are needed.Copyright © 2023 Elsevier Inc.

Dai, Q., et al. (2023). "Antitumor Activity of s-Triazine Derivatives: A Systematic Review." Molecules (Basel, Switzerland) 28(11).
	1,3,5-triazine derivatives, also called s-triazines, are a series of containing-nitrogen heterocyclic compounds that play an important role in anticancer drug design and development. To date, three s-triazine derivatives, including altretamine, gedatolisib, and enasidenib, have already been approved for refractory ovarian cancer, metastatic breast cancer, and leukemia therapy, respectively, demonstrating that the s-triazine core is a useful scaffold for the discovery of novel anticancer drugs. In this review, we mainly focus on s-triazines targeting topoisomerases, tyrosine kinases, phosphoinositide 3-kinases, NADP+-dependent isocitrate dehydrogenases, and cyclin-dependent kinases in diverse signaling pathways, which have been extensively studied. The medicinal chemistry of s-triazine derivatives as anticancer agents was summarized, including discovery, structure optimization, and biological applications. This review will provide a reference to inspire new and original discoveries.

Dai, Y., et al. (2022). "PD-1/PD-L1 Inhibitors Monotherapy for the Treatment of Endometrial Cancer: Meta-Analysis and Systematic Review." Cancer Investigation 40(3): 293-309.
	Purpose: The efficacy of programmed cell death protein 1(PD-1)/Programmed cell death 1 ligand 1 (PD-L1) inhibitors for endometrial cancer remain controversial, and guidelines are inconsistent on which are preferred therapies for advanced disease, or who develop metastases and recurrence. Therefore, we aimed to estimate the efficacy and safety of PD-1/PD-L1 inhibitors in endometrial cancer on a more complete database by adding multiple randomized trials.; Methods: A systematic and comprehensive search was carried out in PD-1/PD-L1 inhibitors monotherapy.; Results: The ORR of PD-1/PDL-1 inhibitors was 29%, and subgroup analysis showed that the pooled ORR of the proficient mismatch repair (pMMR) group was 4% and which was 45% of the deficient mismatch repair (dMMR) group. The DCR of PD-1/PD-L1 inhibitors was 48%, through subgroup analysis, we found that the DCR of the pMMR group was 21% and which was 58% of the dMMR group. The proportion of patients occurring overall adverse events was 65% and grade three or higher adverse events was 14%. The proficient mismatch repair (pMMR) group and the deficient mismatch repair (dMMR) group showed different results.; Conclusion: PD-1/PD-L1 inhibitors had shown little success in the pMMR population and better efficacy in the dMMR population.

Daix, M., et al. (2022). "Extended pelvic resection for gynecological malignancies: A review of out-of-the-box surgery." Gynecologic Oncology 165(2): 393-400.
	The term 'out-of-the-box surgery' in gynecologic oncology was recently coined to describe the resection of tumor growing out of the endopelvic cavity. In the specific case of pelvic sidewall involvement, a laterally extended pelvic resection may be required. As previously defined by Hockel, this resection requires the en bloc removal of structures including the pelvic sidewall muscles, bones, nerves, and/or major vessels. This complex radical procedure leads to tumor-free margins in more than 75% of the patients, with reliable functional results. The rate of recurrence and overall survival are directly correlated with clear resection margins. Progress in imaging, surgical techniques, and perioperative care currently offer the opportunity to attempt surgical curative resection in selected patients for whom palliative therapy was the only alternative. However, the procedure is associated with a high rate of major postoperative complications affecting up to 60% of patients. Multidisciplinary expert centers are the most likely to achieve this complex surgery with favorable oncological outcomes. The aim of this review is to summarize the key issues of out-of-the-box surgery in gynecologic cancer.Copyright © 2022 Elsevier Inc.

Daiyu, Z., et al. (2021). "Effect of metformin on pregnancy outcome and offspring development among women with polycystic ovarian syndrome: a systematic review and meta-analysis."
	
Dalkalitsis, A., et al. (2022). "Inguinal endometriosis: A systematic review." Taiwanese Journal of Obstetrics & Gynecology 61(1): 24-33.
	Inguinal endometriosis is a very rare entity with uncertain pathophysiology, that poses several diagnostic and therapeutic challenges. This study aimed to summarize published literature on the diagnosis and treatment of this condition. Thus, a systematic literature search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library. An effort was made to numerically analyze all parameters included in case reports and retrospective analyses, as well. The typical and atypical features of this condition, investigations used, type of treatment and histopathology were recorded. More specifications about the surgical treatment, such as operations previously performed, type of surgery and treatment after surgery have been acknowledged. Other sites of endometriosis, the presence of pelvic endometriosis and the follow-up and recurrence have been also documented. Overall, the search yielded 61 eligible studies including 133 cases of inguinal endometriosis. The typical clinical presentation includes a unilateral inguinal mass, with or without catamenial pain. Transabdominal or transvaginal ultrasound was typically used as the first line method of diagnosis. Groin incision and exploratory surgery was the treatment indicated by the majority of the authors, while excision of part of the round ligament was reported in about half of the cases. Chemotherapy and radiotherapy were initiated in cases of coexisting endometriosis-related neoplasia. Inguinal recurrence or malignant transformation was rarely reported. The treatment of inguinal endometriosis is surgical and a long-term follow-up is needed. More research is needed on the effectiveness of suppressive hormonal therapy, recurrence rate and its relationship with endometriosis-associated malignancies.; Competing Interests: Declaration of competing interest None. (Copyright © 2021. Published by Elsevier B.V.)

Dallagiovanna, C., et al. (2022). "Effect of letrozole on follicular fluid steroids concentrations in cancer patients undergoing oocyte cryopreservation." Journal of Assisted Reproduction and Genetics 39(5): 1169-1176.
	Purpose: To investigate the impact of letrozole administration on follicular steroid hormones during controlled ovarian hyperstimulation for fertility preservation.; Methods: One hundred and nineteen women with cancer undergoing oocytes retrieval for fertility preservation were recruited. All women underwent ovarian hyperstimulation according to a random start protocol. Those with hormone-sensitive tumors also received letrozole, an aromatase inhibitor aimed at keeping peripheral estrogen levels low. At the time of oocytes retrieval, a sample of follicular fluid was collected and frozen. All samples were assayed concomitantly after thawing, by liquid chromatography tandem mass spectrometry. The concentration of 15 steroid hormones was determined and results were compared between women who did and did not receive letrozole.; Results: Fifty-two women were treated with letrozole, while 67 were not. Statistically significant differences emerged for 12 of the 15 tested steroids. They were the following: cortisol, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), estradiol, androstenedione, testosterone, dihydrotestosterone (DHT), 17-hydroxyprogesterone, progesterone and corticosterone. The most striking differences were observed for testosterone that showed a more than 200-time increase in women receiving letrozole. Estradiol was conversely reduced to a third.; Conclusions: The endocrine microenvironment surrounding oocytes is markedly perturbed by the concomitant assumption of letrozole. Robust clinical evaluation is pressingly needed to rule out any detrimental effect on the chance of live birth with the use of these oocytes. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

D'Alterio, M. N., et al. (2021). "Medical and surgical interventions to improve the quality of life for endometriosis patients: A systematic review." Gynecological Surgery 18(1): 13.
	Endometriosis impairs the quality of life (QoL) of many women, including their social relationships, daily activity, productivity at work, and family planning. The aim of this review was to determine the instruments used to examine QoL in previous clinical studies of endometriosis and to evaluate the effect of medical and surgical interventions for endometriosis on QoL. We conducted a systematic search and review of studies published between January 2010 and December 2020 using MEDLINE. Search terms included "endometriosis" and "quality of life." We only selected studies that used a standardized questionnaire to evaluate QoL before and after medical or surgical interventions. Only articles in the English language were examined. The initial search identified 720 results. After excluding duplicates and applying inclusion criteria, 37 studies were selected for analysis. We found that the two scales most frequently used to measure QoL were the Short Form-36 health survey questionnaire (SF-36) and the Endometriosis Health Profile-30 (EHP-30). Many medical and surgical treatments demonstrated comparable benefits in pain control and QoL improvement. There is no clear answer as to what is the best treatment for improving QoL because each therapy must be personalized for the patient and depends on the woman's goals. In conclusion, women must be informed about endometriosis and given easily accessible information to improve treatment adherence and their QoL.Copyright © The Author(s).

d'Alterio, M. N., et al. (2022). "Pregnancy outcomes in women with polycystic ovarian syndrome." Minerva Obstetrics and Gynecology 74(1): 45-59.
	Polycystic ovarian syndrome (PcOs) is the most common endocrinological disease of reproductive-aged women, with an estimated incidence ranging from 5% to 15%. the clinical manifestations of PcOs are heterogeneous and vary according to the age of the patient. insulin resistance (ir), hyperandrogenism, and obesity are widely assumed to play a pivotal role in the pathophysiological mechanism of PcOs. as previously stated by many conducted meta-analyses, PcOs can cause a rising risk of pregnancy complications, including maternal, fetal, and neonatal complications. Pregnancy-induced hypertension (PiH), preeclampsia (Pe), gestational diabetes mellitus (GdM), spontaneous preterm birth (Ptb), and an increased necessity for a cesarean section (cs) are the most documented maternal implications. regarding fetal outcomes, PcOs has also been correlated with elevated neonatal morbidity, prematurity, fetal growth restriction (FGr), birth weight variations (large for gestational age [lGa] and small for gestational age [sGa]), and transfer to the Neonatal intensive care Unit (NicU). Owing to the variability of the studies performed, the association of PcOs with an elevated risk of adverse pregnancy outcomes is still controversial. this variability is found in the diagnosis and clinical presentations of PCOS, and can be influenced by prepregnancy circumstances and therapies as well as particular population and environmental features. The Amsterdam Consensus Guidelines confirm that obesity and IR can worsen maternal and fetal complications; thus, a closer follow-up should be offered to PcOs women during pregnancy.Copyright © 2021 Edizioni Minerva Medica

Dama Manish, H. and J. Van Lieshout Ryan (2024). "Perinatal Depression: A Guide to Detection and Management in Primary Care." Journal of the American Board of Family Medicine : JABFM 36(6): 1071-1086.
	Introduction: Existing guidelines for primary care clinicians (PCCs) on the detection and management of perinatal depression (PD) contain important gaps. This review aims to provide PCCs with a summary of clinically relevant evidence in the field.; Methods: A narrative literature review was conducted by searching PubMed and PsycINFO for articles published between 2010 to 2023. Guidelines, systematic reviews, clinical trials, and/or observational studies were all examined.; Results: Screening with the Edinburgh Postnatal Depression Scale or Patient Health Questionnaire-9 followed by a diagnostic evaluation for major depressive disorder in probable cases can enhance PD detection. At-risk individuals and mild to moderate PD should be referred for cognitive behavioral therapy or interpersonal psychotherapy when available. Selective serotonin reuptake inhibitors should be used for moderate to severe PD, with sertraline, escitalopram, or citalopram being preferred first. Using paroxetine or clomipramine in pregnancy, and fluoxetine or doxepin during lactation is generally not preferred. Gestational antidepressant use is associated with a small increase in risk of reduced gestational age at birth, low birth weight, and lower APGAR scores, though whether these links are causal is unclear. Sertraline and paroxetine have the lowest rate of adverse events during lactation. Consequences of untreated PD can include maternal and offspring mortality, perinatal complications, poor maternal-infant attachment, child morbidity and maltreatment, less breastfeeding, and offspring developmental problems.; Conclusions: These clinically relevant data can support the delivery of high-quality care by PCCs. Risks and benefits of PD treatments and the consequences of untreated PD should be discussed with patients to support informed decision making.; Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare. (© Copyright by the American Board of Family Medicine.)

Damodaran, S., et al. (2022). "Phase II Study of Copanlisib in Patients with Tumors with PIK3CA Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F." Journal of Clinical Oncology 40(14): 1552-1561.
	PURPOSEActivating mutations in PIK3CA are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an alpha and delta isoform-specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations (with or without PTEN loss).PATIENTS AND METHODSPatients received copanlisib (60 mg intravenous) once weekly on days 1, 8, and 15 in 28-day cycles until progression or toxicity. Patients with KRAS mutations, human epidermal growth factor receptor 2-positive breast cancers, and lymphomas were excluded. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival, 6-month progression-free survival, and overall survival.RESULTSThirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the Protocol. Multiple histologies were enrolled, with gynecologic (n = 6) and gastrointestinal (n = 6) being the most common. Sixty-eight percent of patients had >= 3 lines of prior therapy. The ORR was 16% (4 of 25, 90% CI, 6 to 33) with P =.0341 against a null rate of 5%. The most common reason for protocol discontinuation was disease progression (n = 17, 68%). Grade 3/4 toxicities observed were consistent with reported toxicities for PI3K pathway inhibition. Sixteen patients (53%) had grade 3 toxicities, and one patient (3%) had grade 4 toxicity (CTCAE v5.0). Most common toxicities include hyperglycemia (n = 19), fatigue (n = 12), diarrhea (n = 11), hypertension (n = 10), and nausea (n = 10).CONCLUSIONThe study met its primary end point with an ORR of 16% (P =.0341) with copanlisib showing clinical activity in select tumors with PIK3CA mutation in the refractory setting.Copyright © American Society of Clinical Oncology.

Danaher Brian, G., et al. (2023). "Trial of a patient-directed eHealth program to ameliorate perinatal depression: the MomMoodBooster2 practical effectiveness study." American Journal of Obstetrics and Gynecology 228(4): 453.e451-453.e410.
	Background: Depression is one of the most common complications of childbirth, and is experienced by approximately 17% of pregnant women and 13% of postpartum women. An estimated 85% of these women go untreated-an alarming statistic given the serious consequences for the mother, her child, other family members, and society. Professional societies (the American College of Obstetricians and Gynecologists and American Academy of Pediatrics) have recommended improvements in screening and treatment. Meta-analyses indicate that cognitive behavioral therapy eHealth interventions are efficacious for depression, generally, and for perinatal depression, specifically. Earlier controlled trials have established the effectiveness and acceptability of MomMoodBooster (including an Australian version, MumMoodBooster), an eHealth program for ameliorating postpartum depression.; Objective: This study aimed to evaluate the effectiveness of a perinatal version of MomMoodBooster encompassing both prenatal and postpartum content in a healthcare delivery setting already providing universal screening and referral of at-risk patients as part of routine care.; Study Design: A practical effectiveness study randomly assigned 95 pregnant and 96 postpartum women screened as depressed and satisfying eligibility criteria to experimental groups: the healthcare organization's perinatal depression care program (routine-care group) and routine care+MomMoodBooster2 program (eHealth group). Eligibility criteria included: pregnant or <1 year postpartum, ≥18 years of age, no active suicidal ideation, access to broadband internet via desktop/laptop, tablet, or smartphone, and English language proficiency.; Results: Intent-to-treat analyses of group effects used fixed-effects growth models to assess 12-week posttest change in outcomes. Results showed that both groups had significantly decreased depression severity, anxiety, stress, and automatic thoughts, and increased behavioral activation and self-efficacy. Relative to the routine-care group, the eHealth group displayed significantly greater decreases in depression severity and stress. These group comparisons were not moderated by depression severity (screening or baseline), anxiety, stress, or pregnant/postpartum status. Almost all (93%; n=89) women in the eHealth group visited their program, of whom 99% visited program sessions (M sessions visited=4.3±2.0; M total session duration=73.0±70.2 minutes; 49% viewed all 6 sessions). Among confirmed eHealth program users who provided ratings, 96% (79/82) rated their program as easy to use, 83% rated it helpful, and 93% (76/82) indicated that they would recommend it.; Conclusion: Results support the effectiveness of using MomMoodBooster2 as a treatment option for perinatal women with depression, especially when combined with universal depression screening and referral. Consequently, the eHealth program shows promise as a tool to increase the reach of treatment delivery and to potentially reduce the number of untreated perinatal women with depression. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Daniela, F. and C. Graziele (2021). "Assessment of sexual function in patients with deep endometriosis after surgery."
	
Daniela, F. and Q. Ricardo de Almeida (2021). "Assessment of bowel function in women with deep bowel endometriosis after surgery: systematic review."
	
Daniele, G., et al. (2019). "Prognostic role of chemotherapy-induced neutropenia in first-line treatment of advanced ovarian cancer. A pooled analysis of MITO2 and MITO7 trials." Gynecologic Oncology 154(1): 83-88.
	Background: Chemotherapy-induced neutropenia (CIN) has been associated with improved prognosis in several cancer conditions. Contrasting data have been produced in ovarian cancer. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Danielly, Y., et al. (2022). "The impact of practical women and physical exercise on menopause. A systematic review with meta-analysis."
	
Daniels, J., et al. (2022). "Uterine artery embolization or myomectomy for women with uterine fibroids: Four-year follow-up of a randomised controlled trial." European Journal of Obstetrics and Gynecology and Reproductive Biology: X 13: 100139.
	Objective: To examine the quality of life experienced by women with symptomatic uterine fibroids who had been treated with UAE in comparison to myomectomy. We report the four-year follow-up of the FEMME randomised trial. Two-year follow-up data has been previously reported. Study Design: Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolization were recruited from 29 UK hospitals. Women were excluded if they had significant adenomyosis, any malignancy, pelvic inflammatory disease or had had a previous open myomectomy or uterine artery embolization. Participants were randomised to myomectomy or embolization in a 1:1 ratio using a minimisation algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic, according to clinician preference. Embolization of the uterine arteries was performed according to local practice, under fluoroscopic guidance. The primary outcome measure was the Uterine Fibroid Symptom Quality of Life questionnaire, adjusted for baseline score and reported here at four years post-randomisation. Subsequent procedures for fibroids, pregnancy and outcome were amongst secondary outcomes. Trial registration ISRCTN70772394 https://doi.org/10.1186/ISRCTN70772394 Results: 254 women were randomized, 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolization (98 underwent embolization). At four years, 67 (53%) and 81 (64%) completed UFS-QoL quality of life scores. Mean difference in the UFS-QoL at 4 years was 5.0 points (95% CI -1.4 to 11.5; p = 0.13) in favour of myomectomy. There were 15 pregnancies in the UAE group and 7 in the myomectomy group, with a cumulative pregnancy rate to four years of 15% and 6% respectively (hazard ratio: 0.48; 95% CI 0.18-1.28). The cumulative repeat procedure rate to four years was 24% in the UAE group and 13% in the myomectomy group (hazard ratio: 0.53; 95% CI 0.27-1.05). Conclusion(s): Myomectomy resulted in greater improvement in quality of life compared with uterine artery embolization, although by four years, this difference was not statistically significant. Missing data may limit the generalisability of this result. The numbers of women becoming pregnant were too small draw a conclusion on the effect of the procedures on fertility.Copyright © 2021 The Authors

Daniilidis, A., et al. (2023). "Surgical Management of Ovarian Endometrioma: Impact on Ovarian Reserve Parameters and Reproductive Outcomes." Journal of Clinical Medicine 12(16): 5324.
	Ovarian endometriomas have a negative impact on a patient's reproductive potential and are likely to cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-Mullerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include cystectomy, ablative methods, ethanol sclerotherapy and combined techniques. The optimal surgical approach remains a matter of debate. Our review aimed to summarize the literature on the impact of surgical management of endometrioma on AMH, AFC and fertility outcomes. Cystectomy may reduce recurrence rates and increase chances of spontaneous conception. However, a postoperative reduction in AMH is to be anticipated, despite there being evidence of recovery during follow-up. The reduction in ovarian reserve is likely multi-factorial. Cystectomy does not appear to significantly reduce, and may even increase, AFC. Ablative methods achieve an ovarian-tissue-sparing effect, and improved ovarian reserve, compared to cystectomy, has been demonstrated. A single study reported on AMH and AFC post sclerotherapy, and both were significantly reduced. AMH levels may be useful in predicting the chances of conception postoperatively. None of the aforementioned approaches has a clearly demonstrated superiority in terms of overall chances of conception. Surgical management of endometrioma may, overall, improve the probability of pregnancy. Evidence on its value before medically assisted reproduction (MAR) is conflicting; however, a combination of surgery followed by MAR may achieve the optimal fertility outcome. In view of the complexity of available evidence, individualization of care, combined with optimal surgical technique, is highly recommended.Copyright © 2023 by the authors.

Danis, R., et al. (2022). "Orally Administered Probiotics in the Prevention of Chemotherapy (+/- Radiotherapy)-Induced Gastrointestinal Toxicity: A Systematic Review With Meta-Analysis of Randomized Trials." Integrative Cancer Therapies 21.
	Background: Chemoradiotherapy-induced gastrointestinal toxicity may lead to a significant impairment of the oncological patient's quality of life, as well as to reduced adherence to the treatment, which may have a negative impact on survival and mortality rates. Objective(s): The aim of this review was to investigate whether oral probiotic administration prevents chemotherapy (+/- radiotherapy)-induced gastrointestinal toxicity, particularly diarrhea. Method(s): We searched the MEDLINE, Web of Science, and SCOPUS databases for randomized controlled trials in English published between 1990 and 2020. We conducted statistical data analyses expressing the treatment effect size as a risk ratio (RR) together with a 95% confidence interval (CI). Implications are based on trials rated as having a low risk of bias (RoB). Result(s): We included 8 trials (n = 697 participants), from which 3 studies rated as low RoB contained primary endpoint data; the risk of developing grade 3/4 diarrhea in patients receiving probiotics was reduced by 78% compared to the control group (RR = 0.22 [95% CI 0.05-1.08]; P =.06; n = 114 participants). Probiotics showed preventive effects in patients treated with chemotherapy alone (RR = 0.34 [0.12-0.94]; P =.04, n = 121 participants) and in patients with colorectal cancer (RR = 0.56 [0.34-0.92]; P =.02; n = 208 participants). The reduction in the incidence of overall diarrhea was not significant. Conclusion(s): Probiotics failed to prove a preventive effect of statistical significance against the development of severe and overall diarrhea in cancer patients treated with chemotherapy (+/- radiotherapy). However, we cannot rule out that the effects of probiotics are clinically relevant, especially in certain subgroups of patients. This needs to be clarified in further well-performed studies.Copyright © The Author(s) 2022.

Dankova, I., et al. (2023). "Efficacy and Safety of Platelet-Rich Plasma Injections for the Treatment of Female Sexual Dysfunction and Stress Urinary Incontinence: A Systematic Review." Biomedicines 11(11).
	Introduction: There is no clear evidence in the literature that platelet-rich plasma (PRP) injections improve female sexual dysfunction (FSD) and female stress urinary incontinence (SUI). Objectives: A systematic review was performed to study the efficacy and safety of PRP injections in women with the above pathologies, as well as to explore the optimal dosing, frequency and area of injections, and duration of treatment. Methods: A systematic search on PubMed, Embase and the Cochrane Library database was performed, as well as sources of grey literature from the date of database or source creation to January 2023. After title/abstract and full-text screening, clinical studies on humans evaluating the efficacy of PRP in gynecological disorders using standardized tools were included. Risk of bias was undertaken with RoB-2 for randomized-controlled trials (RCT) and the Newcastle-Ottawa Scale (NOS) for observational studies. Results: Four prospective and one retrospective study explored FSD, while six prospective and one RCT evaluated female SUI. A total of 327 women with a mean age of 51 ± 12 years were included. For FSD, PRP significantly improved the Female Sexual Function Index (FSFI), the Vaginal Health Index (VHI) and the Female Sexual Distress score (FSDS). For SUI, PRP led to a significant improvement in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the Urogenital Distress Inventory (UDI-6). The identified RCT reported a significantly higher mean score of ICIQ-SF (p < 0.05) and UDI-6 (p < 0.01) in the midurethral sling group compared to the PRP injections group. Regarding the risk of bias, the RCT was characterized by high risk, whereas the observational studies were of moderate risk. The protocol for PRP injections for FSD is the injection of 2 mL of PRP into the distal anterior vaginal wall once a month for 3 months. For female SUI, 5-6 mL of PRP should be injected into the periurethral area once a month for 3 months. Conclusions: Despite the promising initial results of PRP injections, the level of current evidence is low due to methodological issues in the available studies. It becomes clear that there is an emerging need for high-quality research examining PRP injections for the treatment of FSD and female SUI.

Dannecker, C. (2021). "HPV vaccination after treatment of cervical intraepithelial neoplasia (CIN/HSIL)." Gynakologe 54(11): 816-819.
	Background: Human papillomavirus (HPV) vaccination can reliably protect against the development of cervical cancer and its precursors. Whether adjuvant HPV vaccination can reduce the recurrence rate after therapy is not yet fully understood. Objective(s): Can a benefit for adjuvant HPV vaccination be proven from the existing data? Methods: Evaluation and comparative summary of three current meta-analyses of adjuvant HPV vaccination after surgical therapy of cervical intraepithelial neoplasia (CIN). Result(s): Three meta-analyses consistently prove that the recurrence rate can be reduced by around 65% by means of adjuvant HPV vaccination after surgical therapy of a CIN. Approximately 2-3% of women vaccinated adjuvantly benefit from vaccination. The number needed to vaccinate is approximately 46. Conclusion(s): Adjuvant HPV vaccination may be recommended.Copyright © 2021, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Danxue, H. and L. Su (2023). "Efficacy and safety of anti‑angiogenic agents in platinum-resistant ovarian cancer: a systematic review and meta-analysis."
	
Dao, D., et al. (2019). "The utility of apparent diffusion coefficients for predicting treatment response to uterine arterial embolization for uterine leiomyomas: a systematic review and meta-analysis." Diagnostic and interventional radiology (Ankara, Turkey) 25(2): 157-165.
	Purpose: Apparent diffusion coefficient (ADC) values, which are derived from diffusion-weighted imaging, have a potential role for predicting treatment response. A systematic review was conducted to examine the value of baseline ADC values for predicting leiomyoma size reduction after uterine arterial embolization (UAE).; Methods: Study selection, quality appraisal and data extraction were conducted independently by two authors. Statistical analyses included the calculation of weighted means and summary correlation coefficients (under the random effects model).; Results: Eleven studies consisting of a total of 258 patients (age, weighted mean±standard deviation [SD], 43.1±10.1 years) were included. The weighted mean±SD ADC value was 1.2±1.5 ×10-3 s/mm2 at baseline (ten studies) and 1.3±2.8 ×10-3 s/mm2 at approximately 6 months after embolization (six studies). The weighted mean percentage leiomyoma volume reduction (VR) at 6 months was 47.1%±35.6% (seven studies). Based on four studies, the weighted summary correlation coefficient for the correlation between baseline ADC and leiomyoma VR at approximately 6 months was not significant (r=0.40; 95% CI, -0.07 to 0.72; I2=69.7%). No associations were found in three of the four studies that examined changes in ADC values as a predictor.; Conclusion: Due to high heterogeneity, it is unclear whether ADC may be useful for predicting treatment responses to UAE.

Daolio, J., et al. (2020). "Uterine transplantation and IVF for congenital or acquired uterine factor infertility: A systematic review of safety and efficacy outcomes in the first 52 recipients." PloS One 15(4): e0232323.
	Uterine transplantation (UTx) associated with IVF restores fertility in women affected by absolute uterine factor infertility (AUFI). Pregnancies achieved both in women undergoing any solid organ transplantation and following IVF are associated with an increased risk of maternal and neonatal complications. This systematic review evaluated this risk in UTx-IVF treated women focusing on the safety and efficacy features of the treatment. Twenty-two studies and three press releases reporting on 52 UTx-IVF treatments were identified. Regarding the safety of treatment, 38/52 (73,1%) of surgical procedures led to the restoration of uterine function in recipients, 12/52 (23,1%) of recipients experienced post-operative complications requiring hysterectomy, and 2/52 (3,8%) of procedures failed before uterine recipients' surgery due to intra-operative complications. Regarding the efficacy of treatment, results focused on transplanted patients showing full recovery of organ functioning: 16/38 (42,1%) of patients achieved a pregnancy, including two women who gave births twice. UTx-IVF pregnancies led to 16 deliveries and all new-borns were healthy. Six out of 16 (37,5%) UTx pregnancies faced major complications during gestation. Preterm births occurred in 10/16 (62,5%) UTx deliveries. Our data indicates that the risk of gestational and delivery complications deserves important consideration in AUFI women receiving UTx-IVF treatments. However, these observations are preliminary and need to be revised after larger series of data are published.; Competing Interests: The authors have declared that no competing interests exist

Darand, M., et al. (2019). "The effect of Nigella sativa on infertility in men and women: A systematic review." Progress in Nutrition 21: 33-41.
	Objective: Black seed (Nigella sativa L.) is a medicinal plant belonging to botanical family of Ranunculaceae. Given the effective role of N. sativa in treating different diseases, the present systematic review aimed to evaluate the effects of N. sativa on the reproductive system. Material(s) and Method(s): The current systematic review was carried out on randomized controlled trials (RCTs) regarding human, animal and in vivo/in vitro studies published between 2014 and 2017. The related articles were collected by searching the databases of Medline, PubMed, Scopus, Science direct, and Google scholar only in English using the search keywords of Nigella sativa, Black Seed, Thymoquinone (TQ), Infertility, Reproductive System and Reproductive Parameters. Review articles, case reports, abstract in symposium and congress were excluded. Result(s): Finally, 24 articles were selected for analyses. The results showed that the treatment with N. sativa has improved the sperm parameters, semen fluid in men and leydig cell count, graph follicle count, corpus luteum and level of sex hormones such as testosterone and progesterone in women (p<0.05). Conclusion(s): According to the findings, N. sativa can improve the reproductive parameters and sex hormones in both genders.Copyright © Mattioli 1885

Darbà, J. and A. Marsà (2022). "Economic Implications of Endometriosis: A Review." PharmacoEconomics 40(12): 1143-1158.
	Endometriosis is a chronic inflammatory disease that can have serious physical and emotional consequences for patients in terms of pain, quality of life, and infertility. Despite affecting about 10% of women, the pathophysiology and economic impact of the disease are not fully understood. This study aimed to review and summarize research articles quantifying the direct and indirect costs of endometriosis in the context of current national and international treatment guidelines. A search including the terms 'endometriosis' AND 'costs' OR 'cost of illness' OR 'cost analysis' OR 'economic burden' was performed, focusing on studies published between January 2000 and May 2022. Total costs, costs of primary and secondary care, productivity losses, and indirect costs were reported. The medical costs of endometriosis were principally registered in secondary care settings, where surgery was the main cost driver. There was considerable variability of populations and study settings, with the overall direct medical cost range of endometriosis from US$1459 to US$20,239 (2022) per patient per year. An increasing trend has been reported in secondary care costs over time; however, not enough data were available at this time to evaluate inpatient and outpatient costs versus treatment strategies. Similarly, further research is required to evaluate the costs and potential savings associated with new therapies. Numerous studies have evaluated the indirect costs of endometriosis in recent years, finding costs between US$4572 and US$14,079 (2022). Currently, limited data are available on the economic burden of the disease at the patient level. (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Daré, B. and Inc (2021). Study of Intravaginal Tamoxifen in PostMenopausal Women With VVA.
	No Results Available Drug: Tamoxifen|Other: Placebo Number of Subjects with Treatment Emergent Adverse Events|Concentration of Tamoxifen in serial plasma collections over multiple timepoints|Evaluation of vaginal cytology|Evaluation of vaginal pH Female Phase 1|Phase 2 17 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Basic Science DARE-VVA-001 March 1, 2023

Daré, B. and Inc (2022). Study of DARE-HRT1 Over 12 Weeks in Healthy PostMenopausal Women.
	No Results Available Device: IVR Dose 1|Device: IVR Dose 2 Number of Participants with Treatment Emergent Adverse Events|Determination of maximum plasma concentration (Cmax)|Determination of time that maximum plasma concentration was observed (tmax)|Determination of steady-state concentration (Css) Female Phase 1|Phase 2 21 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment DARE-HRT1-002 March 23, 2023

Daré, B. and Inc (2023). A Study of Diclofenac Gel in Women With Primary Dysmenorrhea.
	No Results Available Drug: Diclofenac 1%|Drug: Diclofenac 3%|Drug: Placebo Measure the systemic Level of Diclofenac after a single dose of DARE-PDM1|Measure the systemic Level of Diclofenac after three doses of DARE-PDM1|Measure the Vaginal Fluid levels of diclofenac after three doses of DARE-PDM1|Measure the Vaginal Fluid levels of diclofenac after a single dose DARE-PDM1|Number of participants with abnormal vaginal exam findings.|Number of participants with abnormal laboratory test results. Female Phase 1 36 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment DARE-PDM1-001 May 2024

Das, R., et al. (2022). "Randomised Controlled Trial of Particles Used in Uterine fibRoid Embolisation (PURE): Non-Spherical Polyvinyl Alcohol Versus Calibrated Microspheres." Cardiovascular and interventional radiology 45(2): 207-215.
	Purpose: The PURE study is a randomised controlled trial (RCT) comparing the clinical and MRI outcomes of patients treated with non-spherical polyvinyl alcohol, ns-PVA (Contour PVA-Boston Scientific-355-500 & 500-700 microns) versus calibrated hydrogel microspheres (Embozene-Varian Inc-700 & 900 microns) for symptomatic uterine fibroids.; Materials and Methods: Prospective, ethically approved non-sponsored RCT in 84 patients in a single UK tertiary IR unit, ISRCTN registry trial number ISRCTN18191539 in 2013 and 2014. All patients with symptomatic fibroid disease were eligible. UAE followed a standardised protocol with UFS-QOL and contrast-enhanced MRI before and 6 months post UAE. Outcome measures included: (1) Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). (2) Percentage total and dominant fibroid infarction. (3) Uterine and dominant fibroid volume reduction. (4) Volume of embolics.; Results: Sixty-three patients completed the QOL follow-up (33 ns-PVA vs 30 Embozenes), the groups were equivalent at baseline. Patients were followed up for 6 months following UAE. There was no significant difference in symptom scores or HR-QOL between ns-PVA and Embozenes, p = 0.67 and 0.21, respectively. 92.7% of patients treated with ns-PVA achieved > 90% dominant fibroid infarction versus 61.8% treated with Embozenes (p = 0.0016). 66% of patients treated with ns = PVA achieved > 90% total fibroid percentage infarction compared with 35% in the Embozene group (p = 0.011). The mean vials/syringes used were 5.2 with Embozenes versus 4.1 using PVA (p = 0.08).; Conclusion: The PURE study informs IRs regarding the efficacy of embolic agents in UAE, with superior fibroid infarction on MRI using ns-PVA versus Embozenes however no significant difference in clinical outcomes at 6 months after UAE. (© 2022. Crown.)

Dashti, S., et al. (2022). "A randomised controlled trial on the effects of a structural education module among women with polycystic ovarian syndrome on nutrition and physical activity changes." BMC Women's Health 22(1): 277.
	Background: Polycystic ovarian syndrome (PCOS) is a complex metabolic, endocrine and reproductive disorder that has a huge impact on the life of women. To ascertain the effectiveness of health education module among women with PCOS.; Methods: This single-centre, randomised controlled trial was conducted on female staff of the University Putra Malaysia who were diagnosed with PCOS. Subjects were randomly assigned into intervention (n = 34) and control group (n = 35). In the intervention group, they need to take part in 8 education sessions in total over 6 months, and feedback was collected at the end of the session.; Results: Primary outcome was changes in knowledge, attitude and practise of nutrition. Secondary outcomes were eating attitude and behaviour as well as knowledge, attitude and practise towards physical activity. After 6-months of intervention, there was a significant difference observed in nutrition knowledge 1 score (p < 0.001) and nutrition knowledge 2 score (p = 0.01) between intervention and control groups. Similarly, there was a significant difference observed in international physical activity questionnaire score (p = 0.02) between intervention and control groups. However there was no significant changes for attitude and practice of nutrition, eating attitude as well as knowledge, attitude and practise of physical activity.; Conclusions: Our study showed that 6-months of education intervention can improve nutrition and physical activity knowledge. Based on this study, the education module may be considered an effective intervention for women with PCOS.; Trial Registration: Name of the registry: Australian New Zealand Clinical Trials Registry (ANZCTR).; Trial Registration Number: ACTRN12617000135314. Date of registration: 24/01/2017. URL of trial registry record: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372037. (© 2022. The Author(s).)

Dason, E. S., et al. (2023). "Guideline No. 437: Diagnosis and Management of Adenomyosis." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 45(6): 417.
	Objective: To describe the current evidence-based diagnosis and management of adenomyosis.; Target Population: All patients with a uterus of reproductive age.; Options: Diagnostic options include transvaginal sonography and magnetic resonance imaging. Treatment options should be tailored to symptoms (heavy menstrual bleeding, pain, and/or infertility) and include medical options (non-steroidal anti-inflammatory drugs, tranexamic acid, combined oral contraceptives, levonorgestrel intrauterine system, dienogest, other progestins, gonadotropin-releasing analogues), interventional options (uterine artery embolization), and surgical options (endometrial ablation, excision of adenomyosis, hysterectomy).; Outcomes: Outcomes of interest include reduction in heavy menstrual bleeding, reduction in pelvic pain (dysmenorrhea, dyspareunia, chronic pelvic pain), and improvement in reproductive outcomes (fertility, miscarriage, adverse pregnancy outcomes).; Benefits, Harms, and Costs: This guideline will benefit patients with gynaecological complaints that may be caused by adenomyosis, especially those patients who wish to preserve their fertility, by presenting diagnostic methods and management options. It will also benefit practitioners by improving their knowledge of various options.; Evidence: Databases searched were MEDLINE Reviews, MEDLINE ALL, Cochrane, PubMed, EMBASE. The initial search was completed in 2021 and updated with relevant articles in 2022. Search terms included adenomyosis, adenomyoses, endometritis (used/indexed as adenomyosis before 2012), (endometrium AND myometrium) uterine adenomyosis/es, symptom/s/matic adenomyosis] AND [diagnosis, symptoms, treatment, guideline, outcome, management, imaging, sonography, pathogenesis, fertility, infertility, therapy, histology, ultrasound, review, meta-analysis, evaluation]. Articles included randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Articles in all languages were searched and reviewed.; Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations).; Intended Audience: Obstetrician-gynaecologists, radiologists, family physicians, emergency physicians, midwives, registered nurses, nurse practitioners, medical students, residents, and fellows.; Tweetable Abstract: Adenomyosis is common in reproductive-aged women. There are diagnostic and management options that preserve fertility available.; Summary Statements: RECOMMENDATIONS. (Copyright © 2023. Published by Elsevier Inc.)

D'Astous-Gauthier, K., et al. (2021). "Beta-2 Agonists May be Superior to Epinephrine to Relieve Severe Anaphylactic Uterine Contractions." The journal of allergy and clinical immunology. In practice 9(3): 1232-1241.
	Background: Uterine contractions are recognized as a potential manifestation of anaphylaxis, but literature on their proper management is limited. It is widely recognized that anaphylactic reactions can cause uterine contractions, but little is known about their optimal management.; Objective: Review potential treatments for painful uterine contractions associated with anaphylaxis or mast cell activation.; Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed, Embase, and Cochrane were searched in English, French, and Spanish for reports of uterine anaphylaxis published up until July 2020. The search strategy used a combination of Boolean operators and included the following Medical Subject Heading terms and keywords: hypersensitivity; anaphylaxis; mastocytosis; uterus; uterine contraction; pelvic pain; labor, obstetric; labor, premature; and endometriosis.; Results: This systematic review identified 19 studies reporting on 31 cases of painful uterine contractions occurring during anaphylaxis or other events associated with mast cell activation. Nine patients were pregnant. We present 2 additional cases in nonpregnant women, one associated with an oral food challenge and the other associated with oral food desensitization. The most frequent triggers were subcutaneous immunotherapy (14 cases), food (6 cases), and drugs (4 cases). Uterine cramps were associated with systemic symptoms in 24 cases and lasted on average for 2.4 hours. Pretreatment with antihistamines and montelukast generally failed to prevent recurrence, but nonsteroidal anti-inflammatory drugs were used successfully in some reports. Response to intramuscular epinephrine was inconsistent. Data from ex vivo models indicate that epinephrine may paradoxically contribute to uterine contractions through alpha-receptor activity. A small number of cases showed good response to beta-2 agonists.; Conclusions: There is a lack of quality data on painful uterine contractions occurring in the context of anaphylactic reactions and on their optimal management. In the absence of counterindication, use of a beta-2 agonist and premedication with nonsteroidal anti-inflammatory drugs could be the preferred options. (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Datta, A. K., et al. (2019). "Accumulation of embryos over 3 natural modified IVF (ICSI) cycles followed by transfer to improve the outcome of poor responders." Facts, views & vision in ObGyn 11(1): 77-84.
	Background: Alternatives to improve treatment outcomes in poor responders are needed. For this we studied whether multiple (x3) Natural Modified (NM)-IVF(ICSI) cycles followed by an embryo transfer (ET) from the accumulated embryos can improve the treatment outcomes in poor responders.; Method: A retrospective analysis was applied to a pool of participants qualifying as poor responders according to the Bologna criteria. This was performed over a 2-year IVF center database with a Study Group including women with a minimum of 3 cycles of NM-IVF (ICSI) and subsequent vitrified-thawed ET. As a control, 1 NM-IVF (ICSI) cycle with fresh ET was used. The primary outcome accounted was the livebirth rate (LBRs) following one ET; the secondary outcome was clinical pregnancy rates (CPRs), miscarriage and cycle cancellation rates. Comparisons were held over mean numbers by t-test, over median by Mann-Whitney, and categorical data were treated by Chi-square.; Results: The prognosis for livebirth in the study (n=125) and control (n=208) group was equally poor (mean age: 40.2 ± 3.0 vs 40.0 ± 3.3; median AMH: 2.1 vs 2.2 (pmol/L), AFC 4.0 vs 4.0). The LBR was significantly higher with the study protocol (30.6% vs 13.3%; p=0.002), particularly in women aged 35-39 years (31% vs 10.8%; p=0.05) and 40-44 years (26% vs 10.3%; p=0.02). Lower LBR in women aged ≥35 years in the control-group was mainly attributable to the higher miscarriage rate. With significantly more oocytes (mean: 6.5 ± 3.8 vs 2.0 ± 1.4; p <0.0001) and embryos available (mean: 3.6 ± 2.3 vs 0.9 ± 0.7; p<0.0001), only a minority ended up with no ET in the study-group (7.2% vs 35.6%; p<0.0001). None dropped-out while undergoing 3 cycles, whereas no patient opted for further attempts after one standalone cycle.; Conclusion: Accumulation of embryos through 3 NM-IVF cycles before transfer improves livebirth rates and reduces the risk of lacking an embryo for transfer in poor responders aged ≥35 years.; Competing Interests: No funding was required to conduct this study. (Copyright © 2019 Facts, Views & Vision.)

Datta Niloy, R. and S. Bodis (2019). "Hyperthermia with radiotherapy reduces tumour alpha/beta: Insights from trials of thermoradiotherapy vs radiotherapy alone." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 138: 1-8.
	Purpose: Hyperthermia inhibits the repair of irradiation-induced DNA damage and thereby could alter the α/β values of tumours. This study estimates the clinical α/β HTRT values from clinical trials of thermoradiotherapy (HTRT) vs radiotherapy (RT) in recurrent breast (RcBC), head and neck (III/IV) (LAHNC) and cervix cancers (IIB-IVA) (LACC).; Methods: Three recently published meta-analyses for HTRT vs RT in RcBC, LAHNC and LACC were evaluated for complete response (CR). Studies with specified RT dose (D), dose/fraction (d) and corresponding CRs were selected. Tumour biological effective dose (BED) for each study with RT (BED RT ) was computed assuming an α/β RT of 10 Gy. As outcomes were favourable with HTRT, thermoradiobiological BED (BED HTRT ) was calculated as a product of BED RT and %CR HTRT /%CR RT . The α/β HTRT was estimated as Dd/(BED HTRT - D).; Results: 12 trials with 864 patients were shortlisted - RcBC (3 studies, n = 259), LAHNC (5 studies, n = 338) and LACC (4 studies, n = 267). Overall risk difference of 0.28 favoured HTRT (p < 0.001). Mean BED RT and BED HTRT were 64.7 Gy (SD: ±15.5) and 109.5 Gy (SD: ±32.1) respectively and global α/β HTRT was 2.25 Gy (SD: ±0.79). Mean α/β HTRT for RcBC, LAHNC and LACC were 2.05 Gy, 1.74 Gy and 3.03 Gy respectively. On meta-regression, α/β HTRT was the sole predictor for the corresponding risk differences of the studies (coefficient = -0.096; p = 0.03).; Conclusion: Thermoradiobiological effects on the repair of RT induced DNA damage results in reduction in α/β values of tumours. This should be considered to effectively optimize HTRT dose-fractionation schedules in the clinic. (Copyright © 2019 Elsevier B.V. All rights reserved.)

D'Auge, D. G., et al. (2023). "Therapeutic Approaches to Vulvar Cancer: A Review of Literature." Clinical and Experimental Obstetrics and Gynecology 50(7): 143.
	Objective: Vulvar cancer is a rare gynecological cancer that mainly affects postmenopausal women. The aim of this review is to analyze the most recent data available in the literature on the clinical and therapeutic approach to vulvar carcinoma. Mechanism: Studies available in the literature on the therapeutic management of patients with vulvar carcinoma until November 2022 have been screened. A comprehensive search was performed in the PubMed (MEDLINE), EMBASE, SCOPUS and Web of Science databases. Findings in Brief: The approach to vulvar carcinoma has deeply evolved over the years. The management of early-stage vulvar carcinomas is well established and widely shared, while that of advanced and recurrent cancers is a subject of debate. The assessment of the nodal status has changed from the past with the passage from inguinal lymphadenectomy to the removal of only the sentinel node. Conclusion(s): The gold standard for the management of vulvar cancer is surgery, applicable in the first instance in early-stage tumors and after neoadjuvant therapy for larger tumors. Assessment of the nodal state is crucial and the method to be used depends on the degree of suspicious of positive lymph nodes. The prognosis is good if the treatment is applicable as soon as possible.Copyright © 2023 The Author(s).

David, L., et al. (2021). "Effectiveness of magnetic stimulation in the treatment of urinary incontinence: a systematic review."
	
David Paru, S. and M. Kling Juliana (2022). "Moving toward health equity: the influence of race and ethnicity on choice and quality of life of menopause treatment in midlife women." Menopause (New York, N.Y.) 29(12): 1353-1354.
	Competing Interests: Financial disclosure/conflicts of interest: J.M.K. received past funding from Procter & Gamble and Triangle Insights Group. P.D. has nothing to report.

David, V.-C. and P. Rene (2023). "Up front less radical surgery for non-fertility preserving surgery in patients with early-stage cervical cancer: A systematic review."
	
David, V.-C., et al. (2021). "Fertility-sparing surgery after neoadjuvant chemotherapy in cervical tumors larger than 4 cm: A systematic review with individual patient data."
	
Davidson, T. M., et al. (2023). "Results of TRIO-15, a multicenter, open-label, phase II study of the efficacy and safety of ganitumab in patients with recurrent platinum-sensitive ovarian cancer." Gynecologic Oncology 170: 221-228.
	Background: IGF signaling has been implicated in the pathogenesis and progression of ovarian carcinoma (OC). Single agent activity and safety of ganitumab (AMG 479), a fully human monoclonal antibody against IGF1R that blocks binding of IGF1 and IGF2, were evaluated in patients with platinum-sensitive recurrent OC.; Methods: Patients with CA125 progression (GCIG criteria) or measurable disease per RECIST following primary platinum-based therapy received 18 mg/kg of ganitumab q3w. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 by an independent radiology review committee (IRC) and/or GCIG CA125 criteria. Secondary endpoints included clinical benefit rate (CBR), progression free survival (PFS) and overall survival (OS).; Results: 61 pts. were accrued. Objective responses were seen in 5/61 patients (ORR 8.2%, 95% CI, 3.1-18.8) with 1 partial response (PR) by RECIST and 2 complete responses (CR) as well as 2 PR by CA125 criteria. CBR was 80.3% (95% CI, 67.8-89.0%). The median PFS according to RECIST by IRC was 2.1 months (95% CI, 2.0-3.1). The median PFS per RECIST IRC and/or CA125 was 2.0 months (95% CI, 1.8-2.2). The median OS was 21 months (95% CI, 19.5-NA). The most common overall adverse events were fatigue (36.1%) and hypertension (34.4%). Grade 1/2 hyperglycemia occurred in 30.4% of patients. Hypertension (11.5%) and hypersensitivity (8.2%) were the most frequent grade 3 adverse events.; Conclusions: IGF1R inhibition with ganitumab was well-tolerated, however, our results do not support further study of ganitumab as a single agent in unselected OC patients.; Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Davies, B., et al. (2023). "Targeting patient recovery priorities in degenerative cervical myelopathy: design and rationale for the RECEDE-Myelopathy trial-study protocol." BMJ Open 13(3): e061294.
	INTRODUCTION: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE‐Myelopathy aims to test the disease‐modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. METHODS AND ANALYSIS: RECEDE‐Myelopathy is a multicentre, double‐blind, randomised, placebo‐controlled trial. Participants will be randomised to receive either 60‐100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8‐14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. STUDY DESIGN: Clinical trial protocol V.2.2 October 2020. ETHICS AND DISSEMINATION: Ethical approval has been obtained from HRA‐Wales.The results will be presented at an international and national scientific conferences and in a peer‐reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN Number: ISRCTN16682024.

Davis Elizabeth, J., et al. (2022). "First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors." Journal for Immunotherapy of Cancer 10(10).
	Background: OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.; Methods: Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7-1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics.; Results: Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1-9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting &gt;6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs.; Conclusion: No safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors.; Trial Registration Number: NCT02923349.; Competing Interests: Competing interests: EJD reports research funding (institution) from Actuate, BMS, FivePrime, Genentech, Incyte, Karyopharm and TopAlliance Biosciences; honoraria from MJH Life Sciences; and advisory role for Deciphera. JM-L reports lecture fees from Astellas, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche and Sanofi; advisory fees from Bristol-Myers Squibb, Highlight Therapeutics, Novartis, Pierre Fabre, Roche and Sanofi; research grants from Sanofi; travel grants from Bristol-Myers Squibb, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer and Roche. RK reports grants from MSD, Clovis and MSD; advisory role for Basilea, PharmaMar; advisory fees from AstraZeneca, Clovis, Eisai, GSK, Incyte, iTEOS, Pfizer and Roche. DCC reports advisory role for HUYA, Nektar Therapeutics, Pfizer and Werewolf Pharmaceuticals. SPB reports research funding and honoraria from Nucana plc; advisory fees from Amphista and Ellipses; clinical trials funding from Astex, MSD, Redx Pharma, Roche and UCB. DB reports no competing interests. DBC reports advisory role with AbbVie and Rafael Pharmaceuticals; honoraria from OncLive/MJH Life Sciences; research funding (institution) from Advaxis, Array BioPharma, Bristol-Myers Squibb, Celgene, Corcept Therapeutics, EMD Serono, Incyte, Lilly, Rafael Pharmaceuticals and Synta; and travel, accommodations and expenses from AbbVie. MV reports advisory role with Debiopharm and Roche; and travel from Roche. RE reports advisory fees from AZD, Clovis Oncology, Ellipses, GSK, Merck and Shigoni; speakers' fees from AZD, Clovis Oncology, GSK and Roche. PHD and AO report no competing interests. KS reports advisory fees from QED Therapeutics. JEJ, JC and TC report former employment and stock ownership with Incyte. JP and XC report employment and stock ownership with Incyte. JMM reports grants from Amgen, AstraZeneca, Bristol-Myers Squibb, EMD Serono, Immunocore, Incyte, Macrogenics, Merck Sharp & Dohme, Novartis, Polynoma and Sanofi; advisory role with Amgen and Merck Sharp & Dohme; honoraria from EMD Serono and Pfizer; advisory board for Array BioPharma, Bristol-Myers Squibb, Eisai/Merck, EMD Serono, Sanofi/Regeneron and Seagen. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Davis, J. A., et al. (2022). "Understanding Engagement in Digital Mental Health and Well-being Programs for Women in the Perinatal Period: Systematic Review Without Meta-analysis." Journal of Medical Internet Research 24(8): e36620.
	Background: Pregnancy and the postnatal period can be a time of increased psychological distress, which can be detrimental to both the mother and the developing child. Digital interventions are cost-effective and accessible tools to support positive mental health in women during the perinatal period. Although studies report efficacy, a key concern regarding web-based interventions is the lack of engagement leading to drop out, lack of participation, or reduced potential intervention benefits. Objective(s): This systematic review aimed to understand the reporting and levels of engagement in studies of digital psychological mental health or well-being interventions administered during the perinatal period. Specific objectives were to understand how studies report engagement across 4 domains specified in the Connect, Attend, Participate, and Enact (CAPE) model, make recommendations on best practices to report engagement in digital mental health interventions (DMHIs), and understand levels of engagement in intervention studies in this area. To maximize the utility of this systematic review, we intended to develop practical tools for public health use: to develop a logic model to reference the theory of change, evaluate the studies using the CAPE framework, and develop a guide for future data collection to enable consistent reporting in digital interventions. Method(s): This systematic review used the Cochrane Synthesis Without Meta-analysis reporting guidelines. This study aimed to identify studies reporting DMHIs delivered during the perinatal period in women with subclinical mood symptoms. A systematic database search was used to identify relevant papers using the Ovid Platform for MEDLINE, PsycINFO, EMBASE, Scopus, Web of Science, and Medical Subject Headings on Demand for all English-language articles published in the past 10 years. Result(s): Searches generated a database of 3473 potentially eligible studies, with a final selection of 16 (0.46%) studies grouped by study design. Participant engagement was evaluated using the CAPE framework and comparable variables were described. All studies reported at least one engagement metric. However, the measures used were inconsistent, which may have contributed to the wide-ranging results. There was insufficient reporting for enactment (ie, participants' real-world use of intervention skills), with only 38% (6/16) of studies clearly recording longer-term practice through postintervention interviews. The logic model proposes ways of conceptualizing and reporting engagement details in DMHIs more consistently in the future. Conclusion(s): The perinatal period is the optimal time to intervene with strength-based digital tools to build positive mental health. Despite the growing number of studies on digital interventions, few robustly explore engagement, and there is limited evidence of long-term skill use beyond the intervention period. Our results indicate variability in the reporting of both short- and long-term participant engagement behaviors, and we recommend the adoption of standardized reporting metrics in future digital interventions.Copyright © 2022 Journal of Medical Internet Research. All rights reserved.

Daviu, C., et al. (2024). "Impact of FRAilty screening and Geriatric assessment and INtervention in older patients with epithelial Ovarian Cancer: A multicenter randomized clinical trial protocol (FRAGINOC)." Journal of Geriatric Oncology: 101713.
	Introduction: Radical surgery combined with chemotherapy is the only potential curative treatment of patients with advanced epithelial ovarian cancer (EOC). However, 43% of older Danish patients with EOC are not referred to surgery due to frailty, age, or fear of complications. Comprehensive geriatric assessment (CGA) has demonstrated ability to reduce frailty in older patients, but there is a knowledge gap regarding its effect before or during treatment in older adults with EOC. This protocol presents a randomized controlled trial (RCT), which evaluates the effect of CGA-based interventions including individualized physical exercise therapy in older adults with EOC during neoadjuvant chemotherapy (NACT). Material(s) and Method(s): This RCT will include patients aged >=70 years with primary EOC referred to NACT. Patients will be randomized 1:1 to intervention or standard of care, along with neoadjuvant antineoplastic treatment. Stratification for performance status and center of inclusion will be performed. In the intervention arm, a geriatrician will perform CGA and corresponding geriatric interventions and patients will undergo an individualized home-based exercise program managed by a physiotherapist. All patients will be evaluated with Geriatric-8, modified Geriatric-8, clinical frailty scale, and physical tests at randomization. Predictive values (positive/negative) will be evaluated for CGA detected impairments. The primary endpoint is the proportion of patients referred to interval debulking surgery (IDS). Secondary endpoints include the proportion who complete oncological treatment, improvements in physical tests, quality of life measured by European Organization for Research and Treatment of Cancer-Quality of Life questionnaires at inclusion, after three cycles of chemotherapy, and at end of chemotherapy treatment. Furthermore, the association between results of geriatric screening tests, CGA, and physical tests with complication rate and progression free survival will be examined. The primary outcome will be analyzed with logistic regression in the intention-to-treat population. Power calculations reveal the need to enroll 216 patients. Discussion(s): The present study examines whether CGA-based interventions including individualized physical exercise can increase the referral rate for potential curative IDS in older patients with EOC. If successful, this will result in more patients undergoing surgery and completing chemotherapy, preventing complications, and ultimately improving quality of life and survival. The study setup may establish the basis for direct clinical implementation if proven effective.Copyright © 2024 Elsevier Ltd

Davydov, A. I., et al. (2021). "Ethanol sclerotherapy and laparoscopic cystectomy for ovarian endometriomas. Comparative analysis of efficacy and reproductive outcomes." Voprosy Ginekologii, Akusherstva i Perinatologii 20(6): 110-119.
	Objective. To study and systematize the results of ethanol sclerotherapy in patients with ovarian endometriomas and perform a comparative analysis of the efficacy of sclerotherapy and cystectomy according to international research publications. Materials and methods. Electronic searching was conducted through Medline, PubMed, Google Scholar, ClinicalTrials, and Cochrane Library databases for cohort studies and randomized controlled trials only. A systematic review was performed using preferred reporting items for systematic reviews and meta-analyses (PRISMA). A total of 626 articles were reviewed. The Cochrane Collaboration's tool was used to assess the quality of the studies. Results. It was shown that ethanol sclerotherapy for ovarian endometriomas bears the lowest risk in terms of surgical complications; it is highly economical in combination with maximum fertility preservation, which is especially relevant in assisted reproductive technology programs. The effectiveness of this method is largely determined by the conditions for its use, as well as by the time of ethanol exposure (optimally not less than 7 minutes). At the same time, ethanol puncture of endometrial cysts is not a monotherapy, and its outcome is greatly influenced by the adequacy of postoperative hormonal treatment. The use of 30 microg ethinylestradiol + 2 mg dienogest was shown to be promising. Conclusion. Ethanol sclerotherapy for ovarian endometriomas should be performed in accordance with the developed conditions and indications for its use in combination with postoperative hormonal treatment.Copyright © 2021, Dynasty Publishing House. All rights reserved.

Dawkins, B., et al. (2024). "Cost-Effectiveness of eRAPID eHealth Intervention for Symptom Management During Chemotherapy." JCO oncology practice: OP2300498.
	PURPOSE: A randomized controlled trial of online symptom monitoring during chemotherapy with electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) system found improved symptom control and patient self-efficacy, without increasing hospital admissions and visits. The aim of this study was to evaluate the cost-effectiveness of the eRAPID eHealth intervention compared with usual care for patients receiving systemic treatment for colorectal, breast, or gynecologic cancers in the United Kingdom. METHOD(S): An embedded economic evaluation was conducted alongside the trial evaluating the effectiveness of eRAPID from health care provider and societal perspectives. Costs and quality-adjusted life-years (QALYs) of patients were compared over 18 weeks of the trial. Incremental cost-effectiveness ratios (ICERs) were estimated and compared with the National Institute for Health and Care Excellence cost-effectiveness threshold. Uncertainty around the ICER was explored using nonparametric bootstrapping and sensitivity analyses. Follow-up data were collected 12-months after random assignment for a subset of the study sample to conduct exploratory analysis of potential longer-term effects. RESULT(S): Patients in the eRAPID group had the highest QALY gain and lowest costs over 18 weeks. Although differences were small and not statistically significant, eRAPID had a 55%-58% probability of being more cost-effective than usual care. Patient out-of-pocket costs were lower in the eRAPID group, indicating eRAPID may help patients access support needed within the National Health Service. Exploratory 12-months analysis showed small differences in costs and QALYs, with higher QALY gains in the eRAPID group but also higher costs. Exploratory subgroup analysis by disease status indicated that the eRAPID intervention was cost-effective for patients with early-stage cancers but not for patients with metastatic disease. CONCLUSION(S): Despite small differences in QALYs and costs, the analyses show potential cost-effectiveness of online symptom monitoring, when added to usual care, particularly during adjuvant systemic treatment for early-stage cancers.

De Angelis Maria, C., et al. (2022). "Fertility outcomes after hysteroscopic removal of intrauterine leiomyomas and polyps." Minerva Obstetrics and Gynecology 74(1): 3-11.
	Thanks to the progress of science, it is now understood that a successful implantation not only depends on the quality of the embryo, but also on having a receptive endometrium. During the years, several authors have reviewed the important role of the uterine factor, ranging from the congenital anomalies, such as uterine septa and subsepta, and acquired conditions such as endometrial polyps and submucous myomas. Currently, hysteroscopy has proved to be a powerful and accurate tool for visualizing the uterine cavity and treating intrauterine pathologies. This review of the literature aims to report the current available data on the effects of the two most common endouterine pathologies (i.e. endometrial polyps and submucous myomas) and the impact of hysteroscopic removal on fertility outcomes. To date, the low number of randomized controlled trials available does not yet make it possible to give a definitive answer on what are the reproductive outcomes following treatment of endometrial polyps and leiomyomas. Nevertheless, existing evidence points to a benefit of removal of these two pathologies in infertile women, mostly when they have a history of recurrent pregnancy loss. Further studies are needed to demonstrate that surgical treatments of endometrial polyps and myomas could improve not only the morphology but also the function of the uterine cavity before undergoing any assisted fertility treatment.

de Bree, E. and D. Michelakis (2020). "An overview and update of hyperthermic intraperitoneal chemotherapy in ovarian cancer." Expert Opinion on Pharmacotherapy 21(12): 1479-1492.
	Introduction: Despite, the strong rationale and evidence of the benefit of postoperative intraperitoneal chemotherapy in advanced ovarian cancer, it has not been widely adopted, mainly due to its high morbidity and logistical difficulties. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a more tolerable and technically feasible method of intraperitoneal chemotherapy, whereas other potential advantages include homogenous drug distribution, application before tumor regrowth and combination with hyperthermia, which is directly cytotoxic and enhances the efficacy of many drugs. Areas covered: In this review, the authors explain the rationale and indications for cytoreductive surgery (CRS) and HIPEC in advanced ovarian cancer. Data of major clinical studies, meta-analyses, and recent randomized trials are discussed. Expert opinion: After many encouraging clinical studies and meta-analyses, a recent randomized study demonstrated survival benefit for HIPEC during interval CRS in primary ovarian cancer, without increased morbidity, whereas another implied its benefit in recurrent ovarian cancer. Results of recently completed and numerous ongoing randomized studies will further determine the benefit of HIPEC in ovarian cancer at different time points. Patient selection and appraisal of the best protocols are crucial. The field of gynecological oncology will most likely evolve to include HIPEC eventually as a routine treatment for ovarian cancer.Copyright © 2020 Informa UK Limited, trading as Taylor & Francis Group.

De Cagna, F., et al. (2019). "The Role of Intranasal Oxytocin in Anxiety and Depressive Disorders: A Systematic Review of Randomized Controlled Trials." Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology 17(1): 1-11.
	Several studies have demonstrated the neuromodulating function of oxytocin (OT) in response to anxiogenic stimuli as well as its potential role in the pathogenesis of depression. Consequently, intranasal OT (IN-OT) has been proposed as a potential treatment of anxiety and depressive disorders. The present systematic review aimed to summarize the randomized controlled trials (RCTs) evaluating the effect of IN-OT on anxiety and depressive symptoms. Overall, 15 studies were included, involving patients with social anxiety disorders (7 studies), arachnophobia (1), major depression (3) or post-natal depression (4), and mainly evaluating single-dose administrations of IN-OT. Results showed no significant effects on core symptomatology. Five crossover studies included functional magnetic resonance imaging investigation: one trial showed reduced amygdala hyper-reactivity after IN-OT in subjects with anxiety, while another one showed enhanced connectivity between amygdala and bilateral insula and middle cingulate gyrus after IN-OT in patients but not in healthy controls. More studies are needed to confirm these results. In conclusion, up to date, evidence regarding the potential utility of IN-OT in treating anxiety and depression is still inconclusive. Further RCTs with larger samples and long-term administration of IN-OT are needed to better elucidate its potential efficacy alone or in association with standard care.

De Felice, F., et al. (2020). "Pembrolizumab for advanced cervical cancer: safety and efficacy." Expert Review of Anticancer Therapy 21(2): 1-8.
	Introduction: Pembrolizumab is an immune checkpoint inhibitor with high specificity for binding to the programmed cell death 1 (PD-1) receptor. It has been approved by the FDA in patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express the programmed cell death ligand 1 (PD-L1). Areas covered: Clinical studies of pembrolizumab in cervical cancer were analyzed and discussed. Data were obtained by searching for English peer-reviewed articles on PubMed, clinical trials registered on clincaltrials.gov and related abstracts on the ASCO meeting library. The aim was to review the status of pembrolizumab, the published and ongoing trials, and its safety and efficacy. Expert opinion: Pembrolizumab may ultimately represent a treatment of choice for advanced cervical cancer with PD-L1 expression, both in metastatic and recurrent setting. However, it is essential to better identify and characterize patients that will benefit the most.

De Felice, F., et al. (2021). "Evolution of Clinical Trials in Ovarian Cancer Management over the Past 20 Years: Never Settle Down, Always Go Beyond." Journal of oncology 2021: 1682532.
	Purpose: A practice synthesis of available evidence-based medicine data in ovarian cancer (OC), aiming to provide directions for future research.; Materials and Methods: We performed a systematic review. PubMed was searched for relevant OC trials between January 2000 and December 2019.; Results: Out of 865 references screened, 199 trials were found eligible for inclusion. Most trials were multicenter (83.9%). There was a trend reduction in the number of patients enrolled/per study over the years. Studies testing targeted/biological therapies dominated the second decade (60 trials in 2010-2019 versus 2 trials in 2000-2009). The proportion of trials with positive survival and clinical outcomes significantly increased from 23.8% in early 2000s to 54.1% in the last 5 years. Trials with histology/molecular biomarker criteria were more likely to meet progression-free survival endpoint than those without these selection criteria (69.2% versus 32.6%).; Conclusion: This systematic review suggests a trend of increased positive studies, mainly linked to precision medicine.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2021 Francesca De Felice et al.)

De Gracia, S., et al. (2023). "Serious Complications and Recurrence following Sacrospinous Ligament Fixation for the Correction of Apical Prolapse." Journal of Clinical Medicine 12(2): 468.
	Objective: To evaluate the rates of serious complications and reoperation for recurrence following sacrospinous ligament fixation (SSLF) for apical pelvic organ prolapse. Method(s): This was a national registry ancillary cohort comparative study. The VIGI-MESH registry includes data from 24 French health centers prospectively collected between May 2017 and September 2021. Time to occurrence of a serious complication or reoperation for genital prolapse recurrence was explored using the Kaplan-Meier curve and Log-rank test. The inverse probability of treatment weighting, based on propensity scores, was used to adjust for between-group differences. Result(s): A total of 1359 women were included and four surgical groups were analyzed: Anterior SSLF with mesh (n = 566), Anterior SSLF with native tissue (n = 331), Posterior SSLF with mesh (n = 57), and Posterior SSLF with native tissue (n = 405). Clavien-Dindo Grade III complications or higher were reported in 34 (2.5%) cases, with no statistically significant differences between the groups. Pelvic organ prolapse recurrence requiring re-operation was reported in 44 (3.2%) women, this was higher following posterior compared with anterior SSLF (p = 0.0034). Conclusion(s): According to this large database ancillary study, sacrospinous ligament fixation is an effective and safe surgical treatment for apical prolapse. The different surgical approaches (anterior/posterior and with/without mesh) have comparable safety profiles. However, the anterior approach and the use of mesh were associated with a lower risk of reoperation for recurrence compared with the posterior approach and the use of native tissue, respectively.Copyright © 2023 by the authors.

De Gregorio Miguel, Á., et al. (2023). "A Comparative Study of a Small Series of Patients (50 Patients) with Pelvic Varicose Veins Treated with Plugs Alone or Plugs and Polidocanol." Journal of Clinical Medicine 12(16).
	Level of Evidence: Level 2.; Purpose: To compare the safety and efficacy of vascular plug (VP) and vascular plug and polidocanol foam (VPPF) treatments for embolization in pelvic congestion syndrome (PCS).; Materials and Methods: A comparative, prospective, two-center study enrolled 50 women with PCS from January 2019 to January 2020. The patients were divided into two groups, and embolization was performed with VP (n = 25) and VPPF (n = 25) treatments. The mean age of the patients was 45.6 years ± 6.9. Three clinical parameters were assessed: abdominal pain, dyspareunia, and lower limb pain. The primary outcome (clinical success at 1 yr using a VAS), number of devices, procedure and fluoroscopy times, radiation doses, costs, and complications were compared. The participants were followed-up at 1, 3, 6, and 12 months.; Results: At the 1-year follow-up, clinical success did not significantly differ between the two groups (VP vs. VPPF) regarding the improvement of the symptoms analyzed (pelvic pain, dyspareunia, lower extremity pain, and other symptoms ( p < 0.05)). The mean number of devices per case was 4 ± 1.1 for the VP group and 2 ± 0.31 for the VPPF group ( p < 0.001). No major complications were recorded in either group. The VPPF group had a significantly longer fluoroscopy time (42.8 min ± 14.2 vs. 25.4 min ± 7) and longer radiation dose (VPPF air kerma 839.4 ± 513 vs. VP air kerma 658.4 mGy ± 355 (all p < 0.001)).; Conclusions: Embolization for PCS resulted in pain relief in 90% of patients; the use of polidocanol did not demonstrate changes in the clinical outcome. The use of a VP alone was associated with decreased fluoroscopy time and radiation dose.

De Hoyos, G., et al. (2023). "Efficacy of an environmental enrichment intervention for endometriosis: a pilot study." Frontiers in psychology 14: 1225790.
	Introduction: We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of EE interventions in patients with this painful, inflammatory chronic disease.; Aim: To adapt and test the efficacy of an EE intervention on pelvic pain, mental health, perceived stress, quality of life, and systemic inflammation in endometriosis patients through a randomized clinical trial (RCT).; Materials and Methods: A multidisciplinary team with expertise in physiology, neuroscience, psychology, and women's health adapted and implemented a two-arm RCT comparing an EE intervention with a wait-list control group. Six EE modules administered on alternate weeks were provided to patients in the intervention ( N = 29); controls received education only. Survey data and biospecimens were collected at baseline, end-of-study, and 3-months post-intervention to assess pain (Brief Pain Inventory, BPI), endometriosis-related quality of life-QoL (Endometriosis Health Profile-30, EHP30), anxiety (Generalized Anxiety Disorder 7, GAD7), depression (Patient Health Questionnaire for Depression 8, PHQ8), pain catastrophizing (Pain Catastrophizing Score, PCS), stress (Perceived Stress Scale-14, PSS14), and saliva cortisol levels (AM, PM).; Results: Compared to the wait-list controls, participants in the EE intervention showed significantly decreased GAD-7 scores at the end of the intervention and 3-month follow-up. Depression, perceived stress, and QoL improved at the 3-month follow-up compared to baseline. While pain levels did not improve, they significantly correlated with anxiety, depression, QoL and pain catastrophizing scores.; Conclusion: This pilot RCT demonstrated significant improvements in anxiety and depressive symptoms, QoL, and perceived stress, supporting enriched environments as an integrative psychosocial intervention to be used as adjuvant to the standard of care for endometriosis pain.; Competing Interests: AT-R is employed by Sur180 Therapeutics. CA and IF are co-founders of Sur180 Therapeutics but are not employees. This company was not involved in the study design, collection, analysis, or interpretion of data. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 De Hoyos, Ramos-Sostre, Torres-Reverón, Barros-Cartagena, López-Rodríguez, Nieves-Vázquez, Santiago-Saavedra, Appleyard, Castro and Flores.)

De Jaeghere Emiel, A., et al. (2023). "Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study." Cancer immunology, immunotherapy : CII 72(2): 475-491.
	A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0-31.0) in cervical cancer and 12.0% (90% CI 3.4-28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1-25.7) in cervical cancer and 3.6 weeks (95% CI 3.6-15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0-67.0) and 37.4 weeks (95% CI 19.0-50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity.Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97). (© 2022. The Author(s).)

De Jesus, C. and M. Rodrigues (2022). "[New drug approval: Pembrolizumab plus lenvatinib in second line for patients with advanced or recurrent endometrial cancer]." Bulletin du cancer 109(7-8): 740-741.
	
de la Rosa Consuelo, N., et al. (2022). "Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE)." Trials 23(1): 13.
	Background: Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer.; Objective: To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase.; Results: This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis.; Discussion: The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant's progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021.; Trial Registration: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018. (© 2021. The Author(s).)

De la Torre Perez, E., et al. (2023). "Impact of endometrial compaction on reproductive outcomes after cryotransfer of euploid embryos in a modified natural cycle: protocol for a prospective cohort study." Frontiers in Endocrinology 14: 1285040.
	Introduction: Embryo implantation is a complex and poorly understood process. Most studies to date have focused on the analysis of the endometrium at the end of the estrogenic phase, while the available data on its importance after secretory transformation are limited and inconsistent. Current evidence does not allow for a conclusive interpretation of the changes observed in the pre-implantation endometrium, whether in the natural or replacement cycle, and their relevance in the development of a pregnancy or the implications for clinical practice.; Methods: Multicenter prospective observational cohort study. Based on our sample size calculation, the study group will consist of 206 women (exposed or "compaction" group: 103 women with a decrease of ≥ 5% in endometrial thickness between the estrogenic phase and the day of embryo transfer; non-exposed "non-compaction" group: 103 women with similar or greater endometrial thickness between these time points). The main objective of this study is to compare the ongoing pregnancy rates in natural cycles for euploid embryo transfer in patients who present endometrial compaction at the time of transfer versus those who with a stable or greater endometrial thickness with respect to the estrogenic phase. The estimated duration of the study is 30 months. Inclusion criteria are: 18 to 50 years of age, with primary or secondary infertility, subjected to endometrial preparation in a modified natural cycle for transfer of a genetically euploid blastocyst, from their own oocyte or oocyte donation, with a normal uterine cavity. Exclusion criteria are: uterine or endometrial disease (e.g., multiple myomatosis, severe adenomyosis, Asherman syndrome, refractory endometrium), conditions that prevent correct ultrasound assessment (tilted uterus), or a history of recurrent implantation failure or repeated miscarriages.; Discussion: The findings from this study will provide valuable insights into the potential influence of the "endometrial compaction" phenomenon on reproductive outcomes during natural cycle endometrial preparation. By examining this aspect, we aim to contribute to a better understanding of the factors that may impact successful outcomes in fertility treatments.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 De la Torre Perez, Carratalá-Munuera, Castillo-Farfán, Lledó-Bosch, Moliner-Renau, Bernabeu-García and Bernabeu-Pérez.)

de Lima Nunes, R., et al. (2019). "Lifestyle interventions and quality of life for women with polycystic ovary syndrome: A systematic review and meta-analysis protocol." Medicine 98(50): e18323.
	Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. PCOS has a significant negative impact on the health-related quality of life (HRQoL) and psychological function of women, of which there are reports of high levels of depression in women with PCOS compared to those without PCOS. However, the evidence surrounding the effects of exercise and/or dietary intervention participation on the HRQoL of women with PCOS is limited. Therefore, our objective is to examine the effects of lifestyle interventions (definition include exercise-only, diet-only, exercise + diet and behavioral or combined) on health-related quality of life or general quality of life in women with PCOS.; Methods: We will conduct an update of systematic review and we will follow the recommendations and guidelines of the Cochrane handbook for systematic reviews and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P). We will search the studies in the following databases: MEDLINE. PubMed, PsychINFO, Embase, SportDiscus, Web of Science, Cochrane Database (via Cochrane library), Cochrane Controlled Register of Trials (CENTRAL), and Google Scholar (advance). Manual search of the reference list of identified works, without language and year restrictions. The process of study selection and data extraction will be performed independently by 2 reviewers, with a third reviewer being responsible for the final decision in case of disagreement between the first two. We will use Egger funnel chart to evaluate possible publication biases, in addition, when possible we will perform a subgroup/meta-regression analysis. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).; Protocol Registry: PROSPERO number: CRD42019124176.

de Loos, A. D., et al. (2022). "Metabolic health during a randomized controlled lifestyle intervention in women with PCOS." European Journal of Endocrinology 186(1): 53-64.
	Context: Women with polycystic ovary syndrome (PCOS) have an increased risk of metabolic syndrome (MetS). Both PCOS and MetS are associated with excess weight. Objective(s): To examine the effect of a three-component lifestyle intervention (LSI) with or without short message service (SMS+ or SMS-, respectively) on the prevalence and severity of MetS and metabolic parameters, compared to care as usual (CAU). Design(s): Randomized controlled trial. Method(s): Women diagnosed with PCOS and a BMI >25 kg/m2 (n = 183) were either assigned to a 1-year three-component (cognitive behavioural therapy, diet, and exercise) LSI, with or without SMS support, or to CAU which provided weight-loss advice only. Main outcome measures included changes in the prevalence of MetS, the continuous MetS severity z-score (cMetS z-score), metabolic parameters, and the impact of weight loss. Result(s): After 1 year, the decrease in the cMetS z-score was greater in the SMS+ group than the CAU group (-0.39, P = 0.015). The prevalence of MetS changed with -21.6% (P = 0.037), -16.5% (P = 0.190), and +7.0% (P = 0.509) in both LSI groups and CAU group, respectively. A post hoc analysis for both LSI groups combined vs CAU resulted in a MetS difference of -25.9% (P = 0.046). Moreover, weight loss per se resulted in significantly favourable effects on all metabolic parameters. Conclusion(s): This three-component LSI was more successful in improving metabolic health compared to CAU. Therefore, we recommend this intervention to women with PCOS and excess weight, provided that a clinically relevant weight loss is being pursued.Copyright © 2022 The authors

de Luis, D., et al. (2023). "RS2289487 variation in PERILIPIN gene is a predictor of weight loss and protection against impaired glucose metabolism after a meal-replacement diet in postmenopausal obese females." European Review for Medical and Pharmacological Sciences 27(19): 9355-9362.
	Objective: The PERILIPIN1 (PLIN1) gene encodes an adipocyte-associated protein that modulates weight. The objective was to evaluate the role of the rs2289487 genetic variant of the PLIN1 gene on weight loss and glucose metabolism secondary to a partial meal replacement (pMR) hypocaloric diet.; Patients and Methods: We conducted an interventional study in 111 postmenopausal obese females with body mass index (BMI) > 35 kg/m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks.; Results: After the pMR diet, body weight, (BMI), fat mass, waist circumference, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in these parameters were higher in C allele carriers than in subjects with TT genotype. The percentage of patients who achieved 7.5% weight loss was higher in the C carriers (57.4% vs. 27.6%), (adjusted Odds Ratio 2.14, 95% CI = 1.33-9.40; p = 0.02). The decrease in the percentage of diabetes mellitus or impaired fasting glucose decrease was statistically significant in C allele carriers (30.2% vs. 18.9%; p = 0.01) (OR 0.54, 95% CI = 0.22-0.78; p = 0.02).; Conclusions: The C allele of rs2289487 predicts the magnitude of weight loss resulting from a pMR diet. These adiposity improvements produce a better improvement in insulin resistance and the percentage of impaired glucose metabolism.

de Mattos Lourenço Thais, R., et al. (2019). "A systematic review of reported outcomes and outcome measures in randomized controlled trials on apical prolapse surgery." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 145(1): 4-11.
	Background: Evidence on efficacy and safety of pelvic organ prolapse interventions is variable, and methodological flaws preclude meaningful synthesis of primary research data.; Objective: To evaluate variations in reported outcomes and outcome measures in randomized controlled trials (RCTs) on apical prolapse surgical interventions.; Search Strategy: We searched Cochrane, EMBASE, MEDLINE, and Scopus for English-language articles published from inception to September 30, 2017, using the terms "management", "repair", "operation", and "pelvic organ prolapse".; Selection Criteria: RCTs on apical prolapse surgical treatment.; Data Collection and Analysis: Outcomes and outcome measures were identified and categorized into domains. Studies were evaluated for quality of outcomes. Descriptive statistics were used to calculate frequencies.; Main Results: Forty-three RCTs were included. Seventy-six outcomes and 66 outcome measures were identified. Bladder and ureteric injury were the most commonly reported intraoperative complications (19/31 studies; 61%). Quality of life was assessed by 19 different instruments and questionnaires. Fourteen (45%) of 31 studies used recurrence of prolapse as a postoperative anatomical outcome.; Conclusions: Substantial variation in reported outcomes and outcome measures was confirmed, precluding comparisons across trials and synthesis of the results. Development of a core outcome set will enable high-quality meta-analyses to be performed in the future. PROSPERO registration: CRD42017062456. (© 2019 International Federation of Gynecology and Obstetrics.)

de Oca, M. K. M., et al. (2023). "Use of cryocompression to reduce peripheral neuropathy in gynecologic cancer: A randomized controlled trial (020)." Gynecologic Oncology 176(Supplement 1): S15-S16.
	Objectives: To investigate the efficacy of cryocompression in preventing chemotherapy-induced peripheral neuropathy and to evaluate patient-reported acceptability and tolerability of cryocompression therapy during chemotherapy. Method(s): This was a single institution randomized, self-controlled trial of cryocompression in women with gynecologic cancer being treated with a planned 6 cycles of neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Subjects were randomized to cryocompression applied to the dominant versus non-dominant hand and foot, with no intervention on the opposite side. Compression socks and ice bags were applied to the hand and foot 15 min prior to chemotherapy, throughout the chemotherapy infusion, and 15 min after completion. Outcome measures included patient-reported assessments (Patient Neurotoxicity Questionnaire, Functional Assessment of Cancer Therapy -Taxane [FACT-NTX]), tactile disturbance using the Semmes-Weinstein monofilament test, and tolerability and acceptability using a Likert scale survey. Result(s): Ninety-one subjects were enrolled from January 2021 to August 2022: 5 withdrew prior to intervention, 14 discontinued after 1-2 cycles, 54 completed all study procedures, and 18 remained on-study. The majority had ovarian cancer (49/91, 53.8%), followed by uterine (39/91, 42.9%) and cervical (3/91, 3.3%). Most subjects were White (59/91, 64.8%) and non-Hispanic/Latino (86/91, 94.5%). With each cycle, more subjects had sensory PNQ grade >= C (moderate to severe symptoms) on the control compared to the cryocompression side: 2.2% versus 3.3% at baseline, 8.8% versus 6.6% at cycle 3; 13.2% versus 7.7% at the final assessment. FACT-NTX scores on the control side were consistently higher than on the cryocompression side: 1.3 (SD: 2.0) versus 1.2 (SD: 1.9) at the initial visit, 2.3 (SD: 3.3) versus 1.7 (SD: 2.8) at cycle 3, and 4.2 (SD: 5.2) versus 3.4 (SD: 4.4) at the final visit one month after cycle 6. At each subsequent visit, there were significant differences in FACT-NTX scores by 0.08 points, on average, favoring cryocompression (P = 0.0216). Monofilament scores remained near zero in each group throughout the study. Over 70% of subjects reported that sensations experienced during cryocompression were very tolerable with each cycle, and over 80% "agreed" or "strongly agreed" that cryocompression was acceptable and planned to continue using it during future chemotherapy. From cycle 6 through the final visit, subjects were 39% less likely to have a PNQ >= C on the cryocompression compared to the control side (P = 0.039); the odds of PNQ >= C on the cryocompression compared to the control side was 0.52 at the final visit (P = 0.021). Conclusion(s): Cryocompression reduces subjective measures of chemotherapy-induced peripheral neuropathy, is acceptable and tolerable to patients, and may improve neuropathy-related quality of life for patients with gynecologic cancer. A final statistical analysis is forthcoming.Copyright © 2023

de Oliveira Natália, M., et al. (2023). "A Review on Acupuncture Efficiency in Human Polycystic Ovary/Ovarian Syndrome." Journal of Pharmacopuncture 26(2): 105-123.
	Objectives: Human Polycystic Ovary/Ovarian Syndrome (PCOS), a frequent endocrine pathophysiology among women of fertile age, is associated with woman's lifespan endocrine, metabolic and psychological implications. Long-term usage side effects of allopathic strategies and their low efficacy made complementary medicine treatments a relevant subject for these patients. The main aim of this work is to review the efficiency of the acupuncture treatment reported in the latest studies on literature regarding PCOS patients.; Methods: A comprehensive literature search, in English language, about the use of acupuncture on the management of PCOS, was conducted in October 2020 using EBSCO, Cochrane, PubMed, Medline, Embase, databases for randomised and non-randomised controlled trials between 2015 and 2020 (09/2015-10/2020), following the PRISMA protocol.; Results: This research led us to an analysis, according to PICOS, of six final papers selected among 178 in total. The articles addressed distinct aspects of the PCOS condition, diverse acupuncture techniques and different main and secondary outcomes in agreement to the respective main objective. According to this review, acupuncture seems to be useful for the treatment of this debilitating and chronic health condition which affects millions of women worldwide, many of them part of the workforce in their community.; Conclusion: Despite of the display of these positive results addressing acupuncture treatments to manage PCOS major symptoms - whether they are reproductive, metabolic, or mental health features - more research is urgent. Randomized, double blinded controlled trials with improved quality design and following STRICTA and/or CONSORT recommendations are necessary to engage acupuncture as a standardized and scientific validated technique in PCOS condition.; Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 Korean Pharmacopuncture Institute.)

De Rienzo, G., et al. (2022). "Evaluation of the effect of 100U of Onabotulinum toxin A on detrusor contractility in women with idiopathic OAB: A multicentre prospective study." Neurourology and Urodynamics 41(1): 306-312.
	Aims: Intradetrusor injection of Onabotulinum Toxin A (BTX-A) is a third-line treatment for overactive bladder (OAB). Voiding dysfunction and the need for intermittent catheterization are potential complications, consequent to bladder contractility (BC) decrement. Primary aim: to evaluate BC variation after BTX-A detrusor injection in women with idiopathic OAB. Method(s): A prospective multi-institutional observational study was conducted. Medical history, bladder diary, 24-h pad test, and invasive urodynamic parameters were recorded before and 4-6 weeks after BTX-A 100U administration. BC was measured as Modified Projected Isovolumetric Pressure (PIP1), that is, maximum flow rate (Qmax) + detrusor pressure at Qmax (PdetQmax). Continuous variables were expressed as median and interquartile range. We compared continuous variables using Wilcoxon test and proportions between two times with Fisher exact test. Result(s): No changes in PIP1 were observed (p > 0.05) in 45 women enrolled between January 2018 and September 2019. Median age was 54.6 years. At baseline, 91.1% had urge urinary incontinence, with 4.9 +/- 2.6 daily pads used and a 24-h pad test of 205.4 +/- 70.8 g. Baseline detrusor contractility was normal in all the patients. Postoperatively, an improvement in the 24-h pad test (p < 0.01), daily voids (p < 0.01), and nocturia (p < 0.01) occurred. Urodynamics pointed out a significant reduction of detrusor overactivity rate (p < 0.01) and an increase of median maximum cystometric capacity (p < 0.01). No difference was observed in median Qmax (p > 0.05), PdetQmax (p > 0.05), and PVR (p > 0.05). No patient needed postoperative catheterization. Conclusion(s): The current series provides evidence that detrusor injection of botulinum toxin is an effective option for treating OAB, without causing voiding dysfunction and BC impairment.Copyright © 2021 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC

De Seta, F., et al. (2022). "Provoked Vestibulodynia and Topical Treatment: A New Option." Healthcare (Basel, Switzerland) 10(5).
	Background: Provoked vestibulodynia is commonly associated with dyspareunia and affects 7% to 15% of women. This pathology has major implications on sexual function and quality of life, and several types of treatments are available for its management. However, a consensus has not been reached concerning the best treatment of vulvar pain. The aim of this study was to assess the efficacy and safety of a brand-new product, the vulvar emulgel Meclon ® Lenex, for the management of provoked vestibulodynia and non-infective vulvitis.; Methods: This was a monocentric, prospective, randomized, double-blind and placebo-controlled study. We enrolled 40 women with provoked vestibulodynia; 20 patients received Meclon ® Lenex, whereas the remaining received a placebo. Each woman was assessed subjectively (through questionnaires) and objectively by evaluating vaginal and vulvar symptoms (Friedrichs criteria and Marinoff dyspareunia grade). We evaluated efficacy, safety, compliance and tolerability of the brand-new product vulvar gel Meclon ® Lenex in provoked vestibulodynia.; Results: After administration of Meclon ® Lenex, we evaluated all parameters of the Friedrichs criteria (burning, dyspareunia, erythema, vulvar pain at the 5 o'clock position and 7 o'clock position), as well as the levels of Marinoff dyspareunia. The active treatment showed to be statistically significantly effective ( p value ≤ 0.05) in reducing all symptoms of Friedrichs criteria, vulvar pain and Marinoff dyspareunia.; Conclusion: This prospective study showed that Meclon ® Lenex vulvar emulgel revealed an excellent tolerability and compliance, demonstrating to be a safe and effective option in the treatment of provoked vestibulodynia and non-infective vulvitis.

De Silva, P. M., et al. (2021). "Pain and operative technologies used in office hysteroscopy: A systematic review of randomized controlled trials." Journal of Minimally Invasive Gynecology 28(10): 1699-1711.
	OBJECTIVE: To identify technologies associated with the least operative pain in women undergoing operative office hysteroscopic procedures. DATA SOURCES: MEDLINE, EMBASE, CINAHL and CENTRAL were searched until January 2021 using a combination of keywords "hysteroscop*", "endometrial ablation", "outpatient", "ambulatory", "office" and associated MeSH headings. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) evaluating the effect of hysteroscopic devices on pain experienced by women undergoing operative office hysteroscopy were included. Data were also collected regarding efficacy, procedural time, adverse events and patient/clinician acceptability and/or satisfaction. TABULATION, INTEGRATION AND RESULTS: The search returned 5347 records. Ten studies provided data for review. Two trials compared endometrial ablation using bipolar radiofrequency with thermal balloon energy, with no significant difference in pain observed (p<0.05). Seven trials evaluated technologies for endometrial polypectomy of which four compared energy modalities; miniature bipolar electrode resection against resectoscopy (n=1), morcellation (n=2) and diode laser resection (n=1). Two studies compared hysteroscope diameter and one study compared methods of polyp retrieval. A significant reduction in pain was found using morcellators rather than miniature bipolar electrosurgical devices (p<0.001), 22Fr rather than 26Fr resectoscopes (p<0.001) and 3.5mm fiber-optic hysteroscopes with 7Fr forceps rather than 5mm lens-based hysteroscopes with 5Fr forceps (p<0.05). One study investigating septoplasty showed significant reduction in pain when cold mini-scissors, rather than a miniature bipolar electrode were used (p=0.013). Average procedural times ranged from 5 minutes 28 seconds to 22 minutes. The incidence of adverse events was low and data regarding efficacy and acceptability/satisfaction were limited. CONCLUSION: Pain is reduced when mechanical technologies such as morcellators and scissors are used compared to electrical devices for removing structural lesions in the office. For hysteroscopic and ablative procedures, smaller and quicker devices are less painful. Large-scale RCTs investigating patient pain and experience with modern operative devices in the office setting are urgently needed.

De Souza Mary, J., et al. (2022). "Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial." The American Journal of Clinical Nutrition 115(6): 1457-1472.
	Background: Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad.; Objectives: The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances.; Methods: Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen + Cal, n = 40, mean ± SEM age: 21.3 ± 0.5 y; weight: 55.0 ± 1.0 kg; BMI: 20.4 ± 0.3 kg/m2) who increased energy intake 20%-40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n = 36; mean ± SEM age: 20.7 ± 0.5 y; weight: 59.1 ± 1.3 kg; BMI: 21.3 ± 0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed.; Results: Oligo/Amen + Cal improved energy status [increased body mass (2.6 ± 0.4 kg), BMI (0.9 ± 0.2 kg/m2), fat mass (2.0 ± 0.3 kg), body fat percentage (2.7% ± 0.4%), and insulin-like growth factor 1 (37.4 ± 14.6 ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P < 0.05). Total body and spine aBMD remained unchanged (P > 0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006 g/cm2; 95% CI: -0.011, -0.0002 g/cm2 ; time main effect P = 0.043) and month 12 (-0.011 g/cm2; 95% CI: -0.021, -0.001 g/cm2; time main effect P = 0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006 g/cm2; 95% CI: -0.011, -0.002 g/cm2; time main effect P = 0.004).; Conclusions: Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352 kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen.This trial was registered at clinicaltrials.gov as NCT00392873. (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

de Vrese, M., et al. (2019). "Impact of oral administration of four Lactobacillus strains on Nugent score - systematic review and meta-analysis." Beneficial microbes 10(5): 483-496.
	We aimed at assessing the evidence for an effect on vaginal dysbiosis by oral administration of a mixture of Lactobacillus strains isolated from vaginal microbiota. For this purpose, we systematically reviewed the literature for randomised clinical trials (RCTs) in which the effect of oral administration of a mixture of four Lactobacillus strains ( Lactobacillus crispatus LbV 88 (DSM 22566), Lactobacillus gasseri LbV 150N (DSM 22583), Lactobacillus jensenii LbV 116 (DSM 22567) and Lactobacillus rhamnosus LbV96 (DSM 22560)) on vaginal dysbiosis was examined based on Nugent score. Four RCTs were identified: a double-blind (DB)-RCT in 60 male-to-female transsexual women with neovagina; an open label RCT in 60 pregnant women with herpes virus infection; a DB-RCT in 36 women with bacterial vaginosis; a DB-RCT in 22 postmenopausal breast cancer patients receiving chemotherapy. Only in the three DB-RCTs Nugent score was assessed. The meta-analysis of these trials showed a significant reduction of Nugent score by probiotics compared to placebo in the fixed (standardised mean differences (SMD) -0.561; confidence interval (CI) -0.935 to -0.186; P =0.004 and random effect models (SMD -0.561; CI -0.935 to -0.186; P =0.004). The odds ratio (OR) of the cases presenting with improved Nugent score after probiotics compared to placebo treatment showed a significant effect in the fixed (OR=3.936; CI 1.702 to 9.100; P =0.001) and random effect model (OR=3.902; CI 1.681 to 9.059; P =0.001) Cochran's Q and I 2 statistics showed no heterogeneity. This meta-analysis indicates that the oral intake of the pertinent Lactobacillus strains improves the microbial pattern in vaginal dysbiosis.

de Wall, L. L., et al. (2022). "Study protocol for a parallel-group randomized controlled multi-center trial evaluating the additional effect of continuous ultrasound bladder monitoring in urotherapy for children with functional daytime urinary incontinence (SENS-U trial)." Trials 23(1): 648.
	Background: Lower urinary tract dysfunction or functional urinary incontinence is a common condition with a prevalence up to 21% between 6 and 8 year‐old children. It is associated with an impaired quality of life, lower self‐esteem, and social stigmatization. Urotherapy is the first treatment of choice for functional daytime urinary incontinence (DUI) in children. Alarm therapy can be a part of urotherapy as it provides the child adequate feedback on wetting accidents. Current alarm systems notify either at a set interval or give a notification when wetting has already occurred to prompt the child to go to the toilet. These alarms do not teach the child the interpretation of the bladder sensation preceding wetting accidents. A new wearable bladder sensor, the SENS‐U, recently became available. This is a relative small, wireless ultrasonic sensor, which continuously monitors bladder filling. The SENS‐U is able to provide an alarm at the exact moment voiding is warranted. It facilitates the child to learn the sensation of bladder filling preceding voiding in an easier way, increasing the learning curve throughout treatment. Its additional effect in urotherapy on continence and cost‐effectiveness is to be determined. Methods/design: This is a multi‐center clinical superiority parallel‐group randomized controlled trial including a total of 480 children. Participants between 6 and 16 years of age with functional DUI in which urotherapy is offered as the next treatment of choice are eligible. Four centers, two academic hospitals, and two general care (peripheral) centers are participating. Participants will be randomized at a 1:1:1 ratio into three groups: urotherapy (care as usual), urotherapy with the SENS‐U added for 3 consecutive weeks throughout the training, or urotherapy with a SHAM device for 3 weeks. The primary outcome is number of wetting accidents per week after 3 months of training, compared between the SENS‐U and the SHAM device. The magnitude of the placebo effect will be assessed by comparing the results of the SHAM group versus the control (care as usual) group. Discussion: To our knowledge, this is the first trial studying not only the effect but also the cost‐effectiveness of alarm interventions as commonly added in urotherapy. Trial registration: ISRCTN44345202. Registered on March 2022

de Wolff, M. G., et al. (2021). "Effects of a Midwife-Coordinated Maternity Care Intervention (ChroPreg) vs. Standard Care in Pregnant Women with Chronic Medical Conditions: Results from a Randomized Controlled Trial." International Journal of Environmental Research and Public Health 18(15).
	The proportion of childbearing women with pre-existing chronic medical conditions (CMC) is rising. In a randomized controlled trial, we aimed to evaluate the effects of a midwife-coordinated maternity care intervention (ChroPreg) in pregnant women with CMC. The intervention consisted of three main components: (1) Midwife-coordinated and individualized care, (2) Additional ante-and postpartum consultations, and (3) Specialized known midwives. The primary outcome was the total length of hospital stay (LOS). Secondary outcomes were patient-reported outcomes measuring psychological well-being and satisfaction with maternity care, health utilization, and maternal and infant outcomes. A total of 362 women were randomized to the ChroPreg intervention (n = 131) or Standard Care (n = 131). No differences in LOS were found between groups (median 3.0 days, ChroPreg group 0.1% lower LOS, 95% CI -7.8 to 7%, p = 0.97). Women in the ChroPreg group reported being more satisfied with maternity care measured by the Pregnancy and Childbirth Questionnaire (PCQ) compared with the Standard Care group (mean PCQ 104.5 vs. 98.2, mean difference 6.3, 95% CI 3.0-10.0, p < 0.0001). In conclusion, the ChroPreg intervention did not reduce LOS. However, women in the ChroPreg group were more satisfied with maternity care.

de Zegher, F., et al. (2021). "The relative deficit of GDF15 in adolescent girls with PCOS can be changed into an abundance that reduces liver fat." Scientific Reports 11(1): 7018.
	A prime concern of young patients with Polycystic Ovary Syndrome (PCOS) is the control of body adiposity, given their tendency to gain weight and/or their difficulty to lose weight. Circulating growth-and-differentiation factor-15 (GDF15) facilitates the control of body weight via receptors in the brainstem. C-reactive protein (CRP) and insulin are endogenous GDF15 secretagogues. We hypothesised that PCOS in non-obese adolescents is characterised by low concentrations of circulating GDF15, when judged by the degree of CRP and insulin drive. GDF15 was added as a post-hoc endpoint of two previously reported, randomised studies in non-obese adolescent girls with PCOS (N = 58; 60% normal weight; 40% overweight) who received either an oral oestroprogestogen contraceptive (OC), or a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET) for 1 year; subsequently, all girls remained untreated for 1 year. Adolescent girls with regular menses (N = 20) served as healthy controls. Circulating GDF15, CRP and fasting insulin were assessed prior to treatment, and halfway the on- and post-treatment years. Pre-treatment, the absolute GDF15 concentrations were normal in PCOS girls, but their relative levels were markedly low, in view of the augmented CRP and insulin drives. OC treatment was accompanied by a near-doubling of circulating GDF15 (on average, from 296 to 507 pg/mL) and CRP, so that the relative GDF15 levels remained low. SPIOMET treatment was accompanied by a 3.4-fold rise of circulating GDF15 (on average, from 308 to 1045 pg/mL) and by a concomitant lowering of CRP and insulin concentrations towards normal, so that the relative GDF15 levels became markedly abundant. Post-OC, the relatively low GDF15 levels persisted; post-SPIOMET, the circulating concentrations of GDF15, CRP and insulin were all normal. BMI remained stable in both treatment groups. Only SPIOMET was accompanied by a reduction of hepato-visceral fat (by MRI) towards normal. In conclusion, early PCOS was found to be characterised by a relative GDF15 deficit that may partly explain the difficulties that young patients experience to control their body adiposity. This relative GDF15 deficit persisted during and after OC treatment. In contrast, SPIOMET treatment was accompanied by an absolute and a relative abundance of GDF15, and followed by normal GDF15, CRP and insulin concentrations. The present findings strengthen the rationale to raise the concentrations of circulating GDF15 in early PCOS, for example with a SPIOMET-like intervention that attenuates low-grade inflammation, insulin resistance and ectopic adiposity, without necessarily lowering body weight.Clinical trial registries: ISRCTN29234515 and ISRCTN11062950.

de Zegher, F. and L. Ibáñez (2024). "Insulin sensitisation for polycystic ovary syndrome: High-dose monotherapy versus low-dose combination." Clinical Endocrinology 100(3): 277.
	
Dealberti, D., et al. (2023). "The Use of Methotrexate and Mifepristone for Treatment of Interstitial Pregnancies: An Overview of Effectiveness and Complications." Journal of Clinical Medicine 12(23): 7396.
	Interstitial pregnancy is an unusual and potentially life-threatening form of ectopic pregnancy, accounting for approximately 1-6% of all ectopic pregnancies, with a maternal mortality rate of 2-2.5%. Implantation happens in the proximal portion of the fallopian tube as it passes through the myometrium. The resolution of interstitial pregnancy after medical treatment should be assessed by a decline in serum beta-hCG, which occurs in about 85-90% of cases. Nonetheless, its effectiveness and consequences have been presented through case reports and case series. However, few cases of interstitial pregnancies treated totally medically with the use of methotrexate and mifepristone have been presented in the literature. Complications of this medical treatments have also never been reviewed before. In the present manuscript, we present a case of interstitial pregnancy treated with methotrexate and mifepristone. The patient after treatment developed a uterine arteriovenous malformation, treated with uterine artery embolization. Furthermore, we performed a systematic review of the literature using Scopus, PubMed and Google Scholar. A total of 186 papers were found, and 7 papers which included 10 cases were assessed for eligibility. The systemic medical treatment with the use of methotrexate and mifepristone was effective in 7 of the 10 cases. Two cases of hemoperitoneum following combined methotrexate and mifepristone treatment were reported. The applicability of this medical conservative treatment should be tailored to the patient, taking into account their obstetric history, gestational age at diagnosis and desire for future pregnancies. Complete resolution after this treatment was achieved in most of the cases reported without major complications. The appearance of uterine arteriovenous malformation can be managed conservatively, and we propose uterine artery embolization as an effective treatment of this rare complication.Copyright © 2023 by the authors.

Deb Pratik, Q., et al. (2022). "Angiosarcoma of the Uterus: A Systematic Review." International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 41(5): 496-502.
	Primary uterine angiosarcoma is an extremely rare neoplasm. Due to its rarity, knowledge regarding this malignancy is limited to a few scattered case reports. To better understand the prognostic factors and optimal management of these neoplasms, we have performed a systematic analysis of the disease. A systematic literature search of this entity yielded 25 reported cases of this entity. In addition, we searched the National Cancer Institute Surveillance, Epidemiology, and End Results database to find 4 additional cases and added a case diagnosed in our institution. We analyzed the patients' demographic characteristics and the different treatment protocols utilized to treat this malignancy. Patients were primarily treated by surgery with or without adjuvant chemotherapy and radiotherapy. Survival analysis was performed to examine the role of various factors in the outcome for the patients. There was no correlation with age of diagnosis, or treatment modality used, however, better outcomes were seen in patients presenting with smaller sized tumors. Our study is the first attempt to systematically study this rare malignancy in hopes of leading to a more standardized, evidence-based, and improved treatment protocol.; Competing Interests: The authors declare no conflict of interest. (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Debaudringhien, M., et al. (2022). "Association between recent pregnancy or hormonal contraceptive exposure and outcome of desmoid-type fibromatosis." ESMO Open 7(5): 100578.
	BACKGROUND: The role of both hormonal contraception and pregnancy on the outcomes of desmoid-type fibromatosis (DF) is debatable. MATERIALS AND METHODS: In the present study, we selected female patients of childbearing age from the prospective ALTITUDES cohort. The primary study endpoint was event-free survival (EFS), with an event defined as relapse or progression. We estimated the risk of events according to the use of hormonal contraception [estrogen-progestin (EP) and progestin] and pregnancy status using multivariate time-dependent models, controlling for major confounders. RESULTS: A total of 242 patients (median age, 34.7 years) were included in the present study. The abdominal wall was the most common tumor site (51%). Patients were managed by active surveillance (80%) or surgery (20%). Pregnancy occurred within 24 months before, at the time of, and after DF diagnosis in 33%, 5%, and 10% of the cases, respectively. Exposure to hormonal contraception was documented within 24 months before, at the time of, and after diagnosis in 44%, 34%, and 39% of the cases, respectively. The 2-year EFS was 75%. After adjusting for DF location, tumor size, front-line treatment strategy, and hormonal contraception, we observed an increased risk of events occurring at 24 months after pregnancy [hazard ratio (HR) = 2.09, P = 0.018]. We observed no statistically significant association between the risk of events and current EP exposure (HR = 1.28, P = 0.65), recent EP exposure (within 1-24 months, HR = 1.38, P = 0.39), current progestin exposure (HR = 0.81, P = 0.66), or recent progestin exposure (HR = 1.05, P = 0.91). CONCLUSIONS: In our study, a recent history of pregnancy was associated with an increased risk of progression/relapse in patients with newly diagnosed DF, whereas hormonal contraception did not demonstrate an association with progression/relapse.

Debrabandere, M. L., et al. (2021). "A Review on Mode of Delivery during COVID-19 between December 2019 and April 2020." American journal of perinatology 38(4): 332-341.
	OBJECTIVE: This study aims to review the published literature to determine mode of delivery in pregnant women with coronavirus disease 2019 (COVID-19) and the indications reported for cesarean section early in the pandemic to add information to the current narrative and raise awareness of trends discovered. STUDY DESIGN: A systematic review was conducted by searching PubMed, Scopus, and ScienceDirect databases for articles published between December 2019 and April 29, 2020 using a combination of the keywords such as COVID-19, coronavirus 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pregnancy, vaginal delivery, cesarean section, vertical transmission, management, and guidelines. Peer-reviewed case studies with confirmed SARS-CoV-2 women who delivered were included to determine mode of delivery, indications for cesarean section, and maternal and neonatal characteristics. RESULTS: A review of 36 total articles revealed deliveries in 203 SARS-CoV-2 positive pregnant women. A comparable severity of disease in pregnant versus nonpregnant women was noted, as previously determined. Overall, 68.9% of women delivered via cesarean section, with COVID-19 status alone being a common indication. Maternal COVID-19 may also be associated with increased risk of preterm labor, although neonatal outcomes were generally favorable. Despite eight of 206 newborns testing positive for SARS-CoV-2, there remains no definitive evidence of vertical transmission. CONCLUSION: COVID-19 status alone became a common indication for cesarean delivery early in the pandemic, despite lack of evidence for vertical transmission. The increase in cesarean rate in this data may reflect obstetricians attempting to serve their patients in the best way possible given the current climate of constantly evolving guidelines on safest mode of delivery for the mother, infant, and provider. Upholding current recommendations from trusted organizations as new data are published, while also providing individualized support to expecting mothers on most appropriate mode of delivery, will reduce the amount of unnecessary, unplanned cesarean sections and could lessen the psychological impact of delivering during the COVID-19 pandemic. KEY POINTS: · COVID-19 may result in an increased rate of cesarean delivery for SARS-CoV-2 positive pregnant women.. · COVID-19 is a commonly reported indication for cesarean section, despite management guidelines urging against this.. · Although eight neonates tested positive for SARS-CoV-2, all additional fluid and tissue samples tested negative..

Debray, A., et al. (2023). "Effect of Exercise Training on Blood Pressure in Healthy Postmenopausal Females: A Systematic Review with Meta-analysis." Medicine and Science in Sports and Exercise 55(7): 1317-1325.
	Introduction: The prevalence of hypertension is greater in postmenopausal females compared with males of similar age. Previous meta-analyses of normotensive and hypertensive adults have shown that aerobic exercise training reduces systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). However, the effect of aerobic exercise training on blood pressure specifically within healthy postmenopausal females remains unclear. This systematic review with meta-analysis quantified the effect of aerobic exercise training on resting SBP and DBP in healthy postmenopausal females.; Methods: The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines and was registered in PROSPERO (CRD42020198171). The literature search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL Plus, and SPORTDiscus. Randomized controlled trials involving healthy postmenopausal females with normal or high normal blood pressure and undergoing ≥4 wk of aerobic exercise training were included. The total weighted mean change in SBP and DBP was compared between the exercise and the control interventions. A random-effects model was used to calculate the overall effect sizes of the weighted mean differences and the 95% confidence interval (CI).; Results: Twelve studies were included in the meta-analysis (exercise interventions: n = 357, age = 60 ± 4 yr, baseline SBP/DBP = 128 ± 13/79 ± 8 mm Hg; control interventions: n = 330, age = 60 ± 4 yr, baseline SBP/DBP = 126 ± 11/77 ± 6 mm Hg). Compared with the change observed in response to the control interventions, exercise training significantly reduced SBP (-0.43 mm Hg, 95% CI = -0.78 to -0.09, P = 0.02) and DBP (-0.39 mm Hg, 95% CI = -0.73 to -0.05, P = 0.05).; Conclusions: Aerobic exercise training significantly reduces resting SBP and DBP in healthy postmenopausal females with normal or high normal blood pressure. However, this reduction is small and of uncertain clinical significance. (Copyright © 2023 by the American College of Sports Medicine.)

Decandia, D., et al. (2022). "n-3 PUFA Improve Emotion and Cognition during Menopause: A Systematic Review." Nutrients 14(9).
	Women show an increased risk of cognitive impairment and emotional disorders, such as anxiety and depression, when approaching menopause. Data on risk and protection factors have yielded robust evidence on the effects of lifestyle factors, such as diet, in preserving emotional and cognitive functioning. This review focused on the effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on anxiety, depression, and cognition during the menopausal transition. This systematic review considered all articles published until 31 December 2021, and the search was performed on two databases, PubMed and Scopus. The fields of interest were "menopause", "n-3 PUFA" and "emotional and cognitive aspects". Out of the 361 articles found on PubMed and 283 on Scopus, 17 met inclusion criteria. They encompassed 11 human and 6 animal studies. Most studies reported relieved depressive symptoms in relation to n-3 PUFA intake. While controversial results were found on anxiety and cognition in humans, n-3 PUFA consistently reduced anxiety symptoms and improved cognition in animal studies. Taken together, n-3 PUFA intake shows beneficial effects on emotional and cognitive behaviours during menopause transition. However, further investigations could increase knowledge about the effectiveness of n-3 PUFA on psychological well-being in this delicate period of feminine life.

DeCesaris, C., et al. (2023). "Financial Improvements from Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer Compared to Standard of Care, "SAVE" Trial." International journal of radiation oncology biology physics 117(2 Supplement): S92.
	Purpose/Objective(s): Early-stage endometrial cancer is often managed with hysterectomy followed by adjuvant VCB. Financial toxicity from cancer treatment is a strong driver of adherence. The SAVE trial is a multicenter, prospective randomized trial of standard of care (SoC) VCB doses delivered in 3-5 fractions per physician discretion compared to a 2-fraction course. We report on secondary cost endpoints, quantifying the financial impacts of shorter treatment courses on institutions and participating patients. Materials/Methods: Technical (TechCs), professional (PCs), and total charges (TotCs) were collected prospectively and are reported as raw and Medicare-adjusted charges per patient. Geographic variations were standardized with CMS Geographic Practice Cost Indices (GPCI), and inflation was adjusted using the Consumer Price Index (CPI): Medical Care. Distance to treatment center was calculated from the patient's zip code to the corresponding treatment center. Cost of commutes was estimated through round-trip travel distance multiplied by average gas MPG for new vehicles by treatment year and state. Median income for each patient's zip code was estimated using 5-year Household income in 2021 inflation-adjusted dollars from the US Census. Mann-Whitney U, T- and Chi-square tests were used to compare characteristics between the two groups. Result(s): One hundred eight patients were analyzed. SoC VCB was delivered in 3, 4 and 5 fractions for 27/54 (50%), 11/54 (20%), and 16/54 (30%), respectively. Median total distance traveled per patient for SoC vs. experimental arms was 213 vs 137 miles (p =.12), and median cost of commute for patients was 36.3 vs 18.0 USD (p =.11). Compared to 2-fraction treatment, 5-fraction treatment resulted in longer travel distances (median 462 vs. 137 miles, p < 0.01) and increased travel costs (median 59.3 v. 18.0 USD, p = < 0.01). Median income by zip code for SoC v. experimental arms was 79,704 vs. 79,671 USD (p = 1.0). For SoC v. experimental arms, 11 (20%) vs 7 (13%) of patients had zip codes with median income in the lowest or second lowest quintiles (p = 0.5). Adjusted raw PCs per patient did not differ between SoC vs. experimental arms (9,159$ vs. 7,532$, p = 0.19). TechCs were significantly higher on the SoC arm (35,734$ vs. 24,696$ p = < 0.01), as were TotCs (44,892$ vs. 32,228$, p < 0.01;). Medicare-adjusted PCs, TechCs, and TotCs were higher for the SoC arm (Table 1). Conclusion(s): Two-fraction VCB resulted in fewer treatments per patient, reduced cost of travel compared to longer courses, and an adjusted reduction in healthcare expenditures compared to standard of care. Ongoing work will include assessment of patient-reported financial toxicities.Copyright © 2023

Declercq, A., et al. (2020). "Proposition of standardized protocol for photodynamic therapy for vulvar lichen sclerosus." The Journal of dermatological treatment: 1-26.
	BACKGROUND: Photodynamic therapy (PDT) is an alternative treatment modality for vulvar lichen sclerosus (VLS) which is a chronic inflammatory mucosal condition. In literature, no consensus of optimal parameters of PDT for VLS are reached so far. OBJECTIVES: The aim of this narrative review is to develop a standardized treatment protocol for PDT in VLSMethods: A systematic literature search was conducted to identify studies reporting on PDT in VLS and used treatment parameters, side-effects and clinical outcome were summarized. RESULTS: Thirteen studies used 5-aminolevulinic acid (5-ALA) with concentrations of 20%, 10%, 5% and three studies used methyl aminolevulinate. Generally the light source was red light (median 630 nm). Light dose varied between 9 and 180 J/cm2 and light intensity between 40 and 700 mW/cm2. Incubation period with the photosensitizer ranged from two to six hours. All studies showed a substantial improvement of VLS-related pruritus, burning and pain. CONCLUSION: Based on a literature review we suggest the following protocol for PDT in VLS: 5% 5-ALA as a photosensitizer applied for three hours under occlusion before irradiation at the dose of 120 J/cm2 with red light (590-760 nm) and intensity of 204 mW/cm2.

Dedes, I., et al. (2023). "Radiofrequency Ablation for Adenomyosis." Journal of Clinical Medicine 12(9): 3069.
	Adenomyosis is a common benign gynecologic condition characterized by ectopic endometrial glands and stroma in the myometrium causing pain (dysmenorrhea) and abnormal uterine bleeding. New interventional techniques have been introduced over recent years. This study evaluates the treatment success and side effects of radiofrequency ablation. An electronic literature search in the PubMed, Scopus, and ScienceDirect databases was carried out on the outcomes of pain reduction and, secondarily, on abnormal uterine bleeding, reintervention, reproductive outcome, imaging outcome, and complications. There was a mean decrease in dysmenorrhea pain scores by -63.4 +/- 9.0% at 12 months. Data on other outcome parameters were sparse. No major complications were reported. Radiofrequency ablation represents a promising minimally invasive and organ-preserving treatment in patients with symptomatic adenomyosis. It is associated with clinically meaningful improvement of adenomyosis-related pain in the short term.Copyright © 2023 by the authors.

Deepika, K., et al. (2021). "HCG trigger versus GnRH agonist trigger in PCOS patients undergoing IVF cycles: frozen embryo transfer outcomes." JBRA Assisted Reproduction 25(1): 48-58.
	OBJECTIVE: The use of Gonadotrophin releasing hormone agonist (GnRHa), with freeze-all strategy followed by frozen embryo transfer (FET) has been found to eliminate the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovarian syndrome (PCOS) undergoing IVF cycles. However, physicians still hesitate to routinely use GnRHa as a trigger, replacing human chorionic gonadotrophin (hCG), for concerns of compromised cycle outcome. We aimed to evaluate outcomes following the transfer of embryos in FET cycles obtained from GnRHa trigger in comparison with hCG trigger in PCOS patients of Asian origin. METHODS: Prospective observational cohort study. 210 PCOS patients undergoing IVF in an antagonist protocol who were randomized in the previous study (to evaluate if GnRHa trigger is a better alternative than hCG in PCOS patients to prevent OHSS; Group A: GnRHa trigger (n=92)] and Group B: hCG trigger (n=101)], were followed up in FET cycles to assess the outcomes. RESULTS: The odds of cumulative live birth rate per stimulation cycle favors GnRHa trigger against the hCG trigger [OR=2.15; (CI 1.2-3.83); p=0.008]. A significantly higher number of mature oocytes (19.1±11.7 versus 14.1±4.3; p<0.001) and blastocysts (4.2±1.63 versus 3.26±1.22; p<0.001) were available in the GnRHa group as compared to the hCG group. CONCLUSION: The cumulative live birth rate was better following transfer of frozen-thawed embryos generated from GnRHa-triggered cycles compared to hCG trigger. Hence, in PCOS undergoing IVF, as a good practice point, hCG trigger should be replaced by a GnRHa trigger with vitrification of all embryos followed by FET.

Deepthika, S. H. K., et al. (2022). "MEDICINAL EFFECTS OF NIGELLA SATIVA IN GYNECOLOGICAL DISORDERS: A SYSTEMATIC REVIEW." International Journal of Pharmaceutical Sciences and Research 13(8): 2977-2987.
	Comprehensive search of previously published research was conducted in PubMed, Science Direct, Scopus, and google scholar databases for studies published between 2012 and August 2021. The keywords used in combination to search for articles included Nigella sativa and "Gynecology". In the first stage, the total articles obtained from searching the above databases using the above keywords were pooled together, and duplicate articles were removed. The remaining articles were primarily screened by reading the title and abstracts and selecting the most relevant articles. In the last stage, articles were reviewed again by reading the entire article, and those that did not meet the inclusion requirements were eliminated. A manual search was conducted using the reference list of the included research publications to collect additional data. In the various databases, the literature search found the following number of research articles: PubMed (n=11), Science Direct (n=35), Scopus (n=07), and Google Scholar (n=1070). After removing duplicates, there were 1062 articles. Those articles were further screened first by reading topics and abstracts and secondly, reading full text that did not match the inclusions was removed. After removing those articles, there were 40 articles, and after adding 05 manual search articles, finally, 45 articles were included in the systematic review. Nigella sativa has medicinal benefits for gynecological disorders such as PCOS, menopause-related issues, Hyperprolactinemia, Candidiasis, Trichomoniasis, Cervical cancer, Breast cancer, ovarian cancer, Premenstrual syndrome and Pre-eclampsia. Nigella sativa also improves endometrium, oocyte maturity and quality and reduces ovarian tissue damage without any adverse effects.Copyright © 2022 Society of Pharmaceutical Sciences and Research. All rights reserved.

Deffieux, X., et al. (2024). "Diagnosis and management of complications following pelvic organ prolapse surgery using a synthetic mesh: French national guidelines for clinical practice." European Journal of Obstetrics and Gynecology and Reproductive Biology 294: 170-179.
	Complications associated with pelvic organ prolapse (POP) surgery using a synthetic non-absorbable mesh are uncommon (<5%) but may be severe and may hugely diminish the quality of life of some women. In drawing up these multidisciplinary clinical practice recommendations, the French National Authority for Health (Haute Autorite de sante, HAS) conducted an exhaustive review of the literature concerning the diagnosis, prevention, and management of complications associated with POP surgery using a synthetic mesh. Each recommendation for practice was allocated a grade (A,B or C; or expert opinion (EO)), which depends on the level of evidence (clinical practice guidelines). Preoperative patients' information: Each patient must be informed concerning the risks associated with POP surgery (EO). Hemorrhage, hematoma: Vaginal infiltration using a vasoconstrictive solution is not recommended during POP surgery by the vaginal route (grade C). The placement of vaginal packing is not recommended following POP surgery by the vaginal route (grade C). During laparoscopic sacral colpopexy, when the promontory seems highly dangerous or when severe adhesions prevent access to the anterior vertebral ligament, alternative surgical techniques should be discussed per operatively, including colpopexy by lateral mesh laparoscopic suspension, uterosacral ligament suspension, open abdominal mesh surgery, or surgery by the vaginal route (EO). Bladder injury: When a bladder injury is diagnosed, bladder repair by suturing is recommended, using a slow resorption suture thread, plus monitoring of the permeability of the ureters (before and after bladder repair) when the injury is located at the level of the trigone (EO). When a bladder injury is diagnosed, after bladder repair, a prosthetic mesh (polypropylene or polyester material) can be placed between the repaired bladder and the vagina, if the quality of the suturing is good. The recommended duration of bladder catheterization following bladder repair in this context of POP mesh surgery is from 5 to 10 days (EO). Ureter injury: After ureteral repair, it is possible to continue sacral colpopexy and place the mesh if it is located away from the ureteral repair (EO). Rectal injury: Regardless of the approach, when a rectal injury occurs, a posterior mesh should not be placed between the rectum and the vagina wall (EO). Concerning the anterior mesh, it is recommended to use a macroporous monofilament polypropylene mesh (EO). A polyester mesh is not recommended in this situation (EO). Vaginal wall injury: After vaginal wall repair, an anterior or a posterior microporous polypropylene mesh can be placed, if the quality of the repair is found to be satisfactory (EO). A polyester mesh should not be used after vaginal wall repair (EO). Mesh infection (abscess, cellulitis, spondylodiscitis): Regardless of the surgical approach, intravenous antibiotic prophylaxis is recommended (aminopenicillin + beta-lactamase inhibitor: 30 min before skin incision +/- repeated after 2 h if surgery lasts longer) (EO). When spondylodiscitis is diagnosed following sacral colpopexy, treatment should be discussed by a multidisciplinary group, including especially spine specialists (rheumatologists, orthopedists, neurosurgeons) and infectious disease specialists (EO). When a pelvic abscess occurs following synthetic mesh sacral colpopexy, it is recommended to carry out complete mesh removal as soon as possible, combined with collection of intraoperative bacteriological samples, drainage of the collection and targeted antibiotic therapy (EO). Non-surgical conservative management with antibiotic therapy may be an option (EO) in certain conditions (absence of signs of sepsis, macroporous monofilament polypropylene type 1 mesh, prior microbiological documentation and multidisciplinary consultation for the choice of type and duration of antibiotic therapy), associated with close monitoring of the patient. Bowel occlusion related to non-closure of the peritoneum: Peritoneal closure is recommended after placement of a synthetic me h by the abdominal approach (EO). Urinary retention: Preoperative urodynamics is recommended in women presenting with urinary symptoms (bladder outlet obstruction symptoms, overactive bladder syndrome or incontinence) (EO). It is recommended to remove the bladder catheter at the end of the procedure or within 48 h after POP surgery (grade B). Bladder emptying and post-void residual should be checked following POP surgery, before discharge (EO). When postoperative urine retention occurs after POP surgery, it is recommended to carry out indwelling catheterization and to prefer intermittent self-catheterization (EO). Postoperative pain: Before POP surgery, the patient should be asked about risk factors for prolonged and chronic postoperative pain (pain sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Concerning the prevention of postoperative pain, it is recommended to carry out a pre-, per- and postoperative multimodal pain treatment (grade B). The use of ketamine intraoperatively is recommended for the prevention of chronic postoperative pelvic pain, especially for patients with risk factors (preoperative painful sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Postoperative prescription of opioids should be limited in quantity and duration (grade C). When acute neuropathic pain (sciatalgia or pudendal neuralgia) resistant to level I and II analgesics occurs following sacrospinous fixation, a reintervention is recommended for suspension suture removal (EO). When chronic postoperative pain occurs after POP surgery, it is recommended to systematically seek arguments in favor of neuropathic pain with the DN4 questionnaire (EO). When chronic postoperative pelvic pain occurs after POP surgery, central sensitization should be identified since it requires a consultation in a chronic pain department (EO). Concerning myofascial pain syndrome (clinical pain condition associated with increased muscle tension caused by myofascial trigger points), when chronic postoperative pain occurs after POP surgery, it is recommended to examine the levator ani, piriformis and obturator internus muscles, so as to identify trigger points on the pathway of the synthetic mesh (EO). Pelvic floor muscle training with muscle relaxation is recommended when myofascial pain syndrome is associated with chronic postoperative pain following POP surgery (EO). After failure of pelvic floor muscle training (3 months), it is recommended to discuss surgical removal of the synthetic mesh, during a multidisciplinary discussion group meeting (EO). Partial removal of synthetic mesh is indicated when a trigger point is located on the pathway of the mesh (EO). Total removal of synthetic mesh should be discussed during a multidisciplinary discussion group meeting when diffuse (no trigger point) chronic postoperative pain occurs following POP surgery, with or without central sensitization or neuropathic pain syndromes (EO). Postoperative dyspareunia: When de novo postoperative dyspareunia occurs after POP surgery, surgical removal of the mesh should be discussed (EO). Vaginal mesh exposure: To reduce the risk of vaginal mesh exposure, when hysterectomy is required during sacral colpopexy, subtotal hysterectomy is recommended (grade C). When asymptomatic vaginal macroporous monofilament polypropylene mesh exposure occurs, systematic imaging is not recommended. When vaginal polyester mesh exposure occurs, pelvic +/- lumbar MRI (EO) should be used to look for an abscess or spondylodiscitis, given the greater risk of infection associated with this type of material. When asymptomatic vaginal mesh exposure of less than 1 cm2 occurs in a woman with no sexual intercourse, the patient should be offered observation (no treatment) or local estrogen therapy (EO). However, if the patient wishes, partial excision of the mesh can be offered. When asymptomatic vaginal mesh exposure of more than 1 cm2 occurs or if the woman has sexual intercourse, or if it is a polyester prosthesis, partial mesh excision, either immediately or after local estrogen thera y, should be offered (EO). When symptomatic vaginal mesh exposure occurs, but without infectious complications, surgical removal of the exposed part of the mesh by the vaginal route is recommended (EO), and not systematic complete excision of the mesh. Following sacral colpopexy, complete removal of the mesh (by laparoscopy or laparotomy) is only required in the presence of an abscess or spondylodiscitis (EO). When vaginal mesh exposure recurs after a first reoperation, the patient should be treated by an experienced team specialized in this type of complication (EO). Suture thread vaginal exposure: For women presenting with vaginal exposure to non-absorbable suture thread following POP surgery with mesh reinforcement, the suture thread should be removed by the vaginal route (EO). Removal of the surrounding mesh is only recommended when vaginal mesh exposure or associated abscess is diagnosed. Bladder and ureteral mesh exposure: When bladder mesh exposure occurs, removal of the exposed part of the mesh is recommended (grade B). Both alternatives (total or partial mesh removal) should be discussed with the patient and should be debated during a multidisciplinary discussion group meeting (EO).Copyright © 2024 Elsevier B.V.

Degheili, J. A. and A. P. Dickson (2020). "Childhood and adolescent idiopathic urethritis: what does the current literature say?" Journal of Pediatric Urology 16(3): 276-283.
	Introduction: Idiopathic urethritis (IU) is a known entity in the childhood and adolescent age groups and is described as blood spotting of the underwear in these populations. Typically, IU presents clinically as terminal void haematuria or blood spotting, accompanied with dysuria, occasional suprapubic pain and rarely constitutional symptoms. Sometimes IU may progress to formation of urethral strictures. It carries a high morbidity because of its chronicity and recurrent course, which often persists to puberty. In spite of no single aetiology being confirmed, several treatment approaches have shown some efficacy. Although no consensus has yet been established, the consideration of previous authors' experience and expertise may contribute to the development of a possible unified algorithm. Aim(s): This article considers IU, collecting pertinent data and case series from the literature. The authors attempt to describe all presumptive aetiologies, endoscopic findings with established grading classifications and finally the various treatment modalities proposed. In addition, highlights from the senior's author experience regarding this entity including endoscopic, radiographic and histological images are mentioned. Method(s): Retrospective review and analysis of all relevant articles present on PubMed, SCOPUS and Cochrane Library from the time of inception to the date of first submission. Result(s): A total of 19 series concerning IU have been reported since year 1971 to present time (Table 1). Many aetiologies have been postulated, but some have been refuted, including infectious pathogens. Children with dysfunctional voiding and meatal stenosis are more prone to exhibit IU. A variation in the urethral milieu during the prepubertal period, secondary to systematic hormonal alteration, may lead to squamous cell metaplasia resulting in IU and possible urethral strictures. Grading classifications for IU are described. Up to 20% of IU may develop urethral strictures. Various treatment approaches are discussed. Conclusion(s): A summary of current understanding of the pathogenesis and spectrum of IU has been achieved. Successful treatment can be achieved with steroids and dysfunctional voiding protocols. It may be possible to develop a consensus unified management algorithm.Copyright © 2020 Journal of Pediatric Urology Company

Dekel, S., et al. (2023). "A Systematic Review of Interventions for Prevention and Treatment of Post-Traumatic Stress Disorder Following Childbirth." MedRxiv : the preprint server for health sciences.
	Objective: Postpartum women can develop post-traumatic stress disorder (PTSD) in response to complicated, traumatic childbirth; prevalence of these events remains high in the U.S. Currently, there is no recommended treatment approach in routine peripartum care for preventing maternal childbirth-related PTSD (CB-PTSD) and lessening its severity. Here, we provide a systematic review of available clinical trials testing interventions for the prevention and indication of CB-PTSD.; Data Sources: We conducted a systematic review of PsycInfo, PsycArticles, PubMed (MEDLINE), ClinicalTrials.gov, CINAHL, ProQuest, Sociological Abstracts, Google Scholar, Embase, Web of Science, ScienceDirect, and Scopus through December 2022 to identify clinical trials involving CB-PTSD prevention and treatment.; Study Eligibility Criteria: Trials were included if they were interventional, evaluated CB-PTSD preventive strategies or treatments, and reported outcomes assessing CB-PTSD symptoms. Duplicate studies, case reports, protocols, active clinical trials, and studies of CB-PTSD following stillbirth were excluded.; Study Appraisal and Synthesis Methods: Two independent coders evaluated trials using a modified Downs and Black methodological quality assessment checklist. Sample characteristics and related intervention information were extracted via an Excel-based form.; Results: A total of 33 studies, including 25 randomized controlled trials (RCTs) and 8 non-RCTs, were included. Trial quality ranged from Poor to Excellent. Trials tested psychological therapies most often delivered as secondary prevention against CB-PTSD onset (n=21); some examined primary (n=3) and tertiary (n=9) therapies. Positive treatment effects were found for early interventions employing conventional trauma-focused therapies, psychological counseling, and mother-infant dyadic focused strategies. Therapies' utility to aid women with severe acute traumatic stress symptoms or reduce incidence of CB-PTSD diagnosis is unclear, as is whether they are effective as tertiary intervention. Educational birth plan-focused interventions during pregnancy may improve maternal health outcomes, but studies remain scarce.; Conclusions: An array of early psychological therapies delivered in response to traumatic childbirth, rather than universally, in the first postpartum days and weeks, may potentially buffer CB-PTSD development. Rather than one treatment being suitable for all, effective therapy should consider individual-specific factors. As additional RCTs generate critical information and guide recommendations for first-line preventive treatments for CB-PTSD, the psychiatric consequences associated with traumatic childbirth could be lessened.; Competing Interests: Disclosure Statement: The authors report no conflict of interest.

Del Forno, S., et al. (2023). "Effects of Pelvic Floor Muscle Physiotherapy on Urinary, Bowel, and Sexual Functions in Women with Deep Infiltrating Endometriosis: A Randomized Controlled Trial." Medicina (Kaunas, Lithuania) 60(1).
	Background and Objectives : Endometriosis is a chronic and recurrent disease defined as the presence and proliferation of endometrial glands and stroma outside the uterine cavity. It affects up to 6-10% of women of reproductive age and can be classified into superficial, ovarian, and deep infiltrating endometriosis (DIE). Deep infiltrating endometriosis can be associated with pain symptoms and pelvic floor muscle hypertone. Moreover, it may be responsible of bowel, urinary, and sexual dysfunctions with impairment of women's quality of life. Few studies have investigated the role of physiotherapy in women with DIE. Here, we aimed first to evaluate the effects of pelvic floor physiotherapy (PFP) on urinary, bowel, and sexual functions. Secondly, we aimed to evaluate the effects of ultrasound visual feedback during PFP on pelvic floor and subjective modifications in the frequency of sexual intercourse. Materials and Methods : This randomized controlled trial was conducted between June 2018 and December 2019 at our tertiary center. Nulliparous women with DIE and superficial dyspareunia were enrolled. At first examination, levator hiatal area (LHA) assessed with 3D/4D transperineal ultrasound, pain symptoms, urinary, bowel, and sexual functions were evaluated. Then, women were randomly assigned to no intervention (control group) or treatment with five individual sessions of PFP (experimental group), and after four months women underwent a second examination. Urinary, bowel, and sexual functions were assessed with validated questionnaires at first and second examinations. In particular, the Bristol Female Lower Urinary Tract Symptoms questionnaire was used to evaluate urinary symptoms, the Knowles-Eccersley-Scott-Symptom questionnaire to assess the presence of constipation, and the Female Sexual Function Index to investigate sexual function. Study outcomes were the comparisons among groups in terms of differences in actual changes in median of questionnaire scores between first and second examinations. Results : Thirty women (17 in the experimental group and 13 in the control group) completed the study. No significant differences were found between the two groups regarding urinary, bowel, and sexual functions, although women in the experimental group showed a tendency towards an improvement in constipation symptoms. Conclusion : In women with DIE, PFP does not appear to affect urinary, bowel, and sexual functions. Therefore, despite the improvement in superficial dyspareunia, chronic pelvic pain, and PFM relaxation with high treatment satisfaction, women should be informed about the unclear impact of PFP on urinary, bowel, and sexual functions. Larger studies are necessary to further investigate the impact of PFP on these functions.

Del Mistro, A., et al. (2019). "Five-year risk of CIN3 after short-term HPV-DNA negativity in cytology-negative women: a population-based cohort study." BJOG : an international journal of obstetrics and gynaecology 126(11): 1365-1371.
	Objective: To assess the 5-year risk of high-grade lesions in women with a transient high-risk HPV infection.; Design: Population-based cohort study.; Setting: HPV primary testing within population-based organised cervical cancer screening programmes.; Population: Italian women enrolled in seven pilot projects and attending the second round.; Methods: On the basis of the cytology triage performed on HPV-positive women, immediate colposcopy or HPV repeat at 12 months was recommended. Data were collected at the subsequent round 3-4 years after HPV infection clearance.; Main Outcome Measures: Rates of HPV infection, CIN2+ and CIN3+ detection at subsequent round after HPV clearance, and relative risks (RR) in comparison with HPV-negative women (with 95% confidence interval).; Results: Data on 1230 women (1027 aged 25-64 years and 203 aged 35-64 years) have been analysed. Overall compliance with repeat HPV testing was 84%. In comparison with HPV-negative women, those with a transient HPV infection had higher proportions of HPV positivity (15% versus 3.7%) and of CIN2+ lesions (0.87% versus 0.23%) in round two; most of these (7/10) were CIN2; no cancers were detected, and CIN3 occurred in 3/1230 (0.24%).; Conclusions: HPV-based protocols for cervical cancer screening allow long intervals for HPV-negative women; it is important to monitor the clinical outcome in the women with transient high-risk HPV infection. CIN3 detection is similar to that observed in routine European cytology-based screening programmes (CIN3+: 2.7‰); 5-year intervals may provide reasonable protection but longer intervals are not recommended.; Tweetable Abstract: A screening interval of 5 years (but no longer) appears safe in women with transient HPV detection. (© 2019 Royal College of Obstetricians and Gynaecologists.)

Del Riccio, M., et al. (2023). "The clinical impact of continued smoking in patients with breast and other hormone-dependent cancer: A systematic literature review." Critical Reviews in Oncology/Hematology 184: 103951.
	We conducted a systematic review of studies that investigated whether quitting smoking at or around diagnosis improves survival of patients with hormone-dependent cancers (HDC). Nine studies published in 2013-2022 were included. Studies were very diverse in terms of design, definition of quitters and continued smokers, and prevalence of prognostic factors other than smoking cessation (e.g. patients' demographics, tumour characteristic, and treatments). For breast, ovarian, and endometrial cancer, all included studies found that quitters had better overall, disease specific, and disease-free survival than continued smokers. For prostate cancer, there was no evidence of an association of smoking cessation with improved survival. This literature review provided suggestive evidence that female smokers diagnosed with cancer of the breast, ovary, or endometrium may improve their chances of surviving by stopping smoking. Smoking cessation counselling should become part of standard oncological care for these patients and integrated into breast cancer screening programs. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Delangle, R., et al. (2019). "The Use of microRNAs in the Management of Endometrial Cancer: A Meta-Analysis." Cancers 11(6).
	Introduction: Endometrial cancer (EC) is the most important gynecological cancer in terms of incidence. microRNAs (miRs), which are post-transcriptional regulators implicated in a variety of cellular functions including carcinogenesis, are particularly attractive candidates as biomarkers. Indeed, several studies have shown that the miR expression pattern appears to be associated with prognostic factors in EC. Our objective is to review the current knowledge of the role of miRs in carcinogenesis and tumor progression and their association with the prognosis of endometrial cancer. Materials and Method: We performed a literature search for miR expression in EC using MEDLINE, PubMed (the Internet portal of the National Library of Medicine) and The Cochrane Library, Cochrane databases "Cochrane Reviews" and "Clinical Trials" using the following keywords: microRNA, endometrial cancer, prognosis, diagnosis, lymph node, survival, plasma, FFPE (formalin-fixed, paraffin-embedded). The miRs were classified and presented according to their expression levels in cancer tissue in relation to different prognostic factors. Results: Data were collected from 74 original articles and 8 literature reviews which described the expression levels of 261 miRs in ECs, including 133 onco-miRs, 110 miR onco-suppressors, and 18 miRs with discordant functions. The review identified 30 articles studying the expression pattern of miR in neoplastic endometrial tissue compared to benign and/or hyperplastic tissues, 12 articles detailing the expression profile of miRs as a function of lymph node status, and 14 articles that detailed the expression pattern of miRs in endometrial tumor tissue according to overall survival or in the absence of recurrence. Conclusions: The findings presented here suggest that miR analysis merits a role as a prognostic factor in the management of patients with endometrial cancer.

Delangle, R., et al. (2020). "Anti-NMDA receptor encephalitis associated with ovarian tumor: the gynecologist point of view." Archives of Gynecology and Obstetrics 302(2): 315-320.
	Background: Anti-NMDA receptor antibody (anti-NMDAr) encephalitis, although still a rare condition, is well known to neurologists as it is the leading cause of non-infectious acute encephalitis in young women. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Indeed, in 30-60% of cases in women of childbearing age, it is associated with the presence of an ovarian teratoma, whose removal is crucial in the resolution of symptomatology. Objective(s): Primary objective of our work was to present a review in a very schematic and practical way for gynecologists, about the data on anti-NMDAr encephalitis in terms of epidemiology, clinical symptomatology, treatment and prognosis. The second objective was to propose a decision tree for gynecologists to guide them, in collaboration with neurologists and anesthesiologists, after the diagnosis of NMDAr encephalitis associated with an ovarian mass. Method(s): We conducted an exhaustive review of existing data using PubMed and The Cochrane Library. Then, we illustrated this topic by presenting two typical cases from our experience. Result(s): Anti-NMDA antibody encephalitis association with an ovarian teratoma is common, especially in women of reproductive age. Complementary examinations in search of an ovarian teratoma must therefore be systematic to envisage a possible surgical excision that may improve patient prognosis. Conclusion(s): Anti-NMDA antibody encephalitis should not be ignored by gynecologists whose role in management is central.Copyright © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Delara, R., et al. (2020). "Surgical or imaging lymph node assessment in locally advanced cervical cancer: a systematic review and meta-analysis." Journal of Gynecologic Oncology 31(6): e79.
	Objective: To evaluate the survival impact of imaging vs surgical nodal assessment in patients with cervical cancer stage IB2-IVA prior to definitive chemoradiotherapy (CRT).; Methods: PubMed, MEDLINE, Cochrane Library, and ClinicalTrials.gov were used to search for publications in English and Chinese over a 50-year period. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols was used to conduct this review. Inclusion criteria were studies that compared survival outcomes in International Federation of Gynecology and Obstetrics 2009 stage IB2-IVA cervical cancer patients with pre-therapy pelvic and/or aortic lymphadenectomy (LND) or imaging. One or more of the following modalities were used for nodal assessment: computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT. The National Institutes of Health Quality Assessment Tool was utilized to assess study quality.; Results: The initial search identified 65 studies, and five met the inclusion criteria. There were a total of 1,112 patients. Seven hundred and fifty-four underwent pelvic and/or aortic LND and 358 had imaging. When compared to LND, imaging had a sensitivity and specificity of 88.9% and 22.2% for pelvic lymph node (LN), and 33%-62.5% and 92%-95.5% for para-aortic LN. There were no differences in progression-free survival (PFS) (hazard ratio [HR]=1.13; 95% confidence interval [CI]=0.73-1.74; I²=75%; p<0.01) and overall survival (OS) (HR=1.06; 95% CI=0.66-1.69; I²=75%; p<0.01) between surgical and imaging nodal assessment.; Conclusions: Imaging and surgical nodal assessment has comparable PFS and OS in patients with cervical cancer stage IB2-IVA.; Trial Registration: PROSPERO Identifier: CRD42020155486.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Delecourt, C., et al. (2022). "Benefits of AirSeal System in Laparoscopic Hysterectomy for Benign Condition: a Randomized Controlled Trial." Journal of Minimally Invasive Gynecology 29(8): 1003‐1010.
	STUDY OBJECTIVE: To compare the AirSeal insufflation system with the standard insufflation system for postoperative abdominal pain after laparoscopic hysterectomy for benign pathology. DESIGN: Randomized controlled trial. SETTING: Teaching Hospital La Conception, Marseille, France, February 2018 to July 2020. PATIENTS: A total of 80 patients scheduled for a laparoscopic hysterectomy for benign pathology (40 per group). INTERVENTION: Laparoscopic hysterectomy using the AirSeal insufflation system with a pneumoperitoneum between 8 and 10 mm Hg compared with the standard insufflation system with a pneumoperitoneum between 12 and 15 mm Hg. MEASUREMENTS AND MAIN RESULTS: The primary end point was abdominal pain at 6 hours after the end of surgery, assessed by a Simple Numerical Scale from 0 to 10. The secondary end points were intraoperative (operating time and difficulty of the surgery felt by the operator), early postoperative (intensity of abdominal and scapular pain at H0 [end of surgery], H2 [two hours after the end of surgery, H12 [twelve hour after the end of surgery], H24 [twenty four hours after the end of surgery], H48 [fourty eight hours after the end of surgery]), and late postoperative (late postoperative complication, estimated time to return to normal life, and overall patient satisfaction assessed by the SF‐12 general health survey). The median values for abdominal pain were not different between the 2 groups at 6 hours (AirSeal group median, 0; interquartile range, 2 vs standard laparoscopy group median, 1; interquartile range, 2; p = .41). The abdominal and scapular pain values were similar in both groups at all postoperative times. There were no differences between the groups regarding secondary end points. CONCLUSION: Use of the AirSeal insufflation system with low‐pressure pneumoperitoneum in laparoscopic hysterectomy for a benign indication did not reduce postoperative abdominal and scapular pain.

Deligiannidis, K., et al. (2023). "Improvement in HAMD-17 Subscale Scores with 14-Day Treatment Course of Zuranolone in Postpartum Depression: Results from the SKYLARK Study." Obstetrics and Gynecology 141(5 Supplement 1): 64S-65S.
	INTRODUCTION: Postpartum depression (PPD) is a serious perinatal complication. SKYLARK (phase 3, randomized, double-blind, placebo-controlled trial [NCT04442503]) evaluated zuranolone, an investigational, neuroactive steroid positive allosteric modulator of both synaptic and extrasynaptic GABA(A) receptors, in adult patients with PPD. The primary endpoint, change from baseline (CFB) in HAMD-17 total score at day 15, was met. Zuranolone was generally well tolerated. The HAMD-17 can be divided into subscales that group specific items from the HAMD-17 scale that measure different aspects of depression presentation. Here, we present HAMD-17 subscale data from SKYLARK. METHOD(S): Patients aged 18-45 years with severe PPD (HAMD 17 total score $26) were randomized 1:1 to oral, once-daily zuranolone 50 mg or placebo for 14 days. The secondary endpoint was day 15 CFB in HAMD-17 subscale (Core Depression, Anxiety, Bech-6, Maier) scores. Subscales were analyzed separately by a mixed-effects model for repeated measures. Institutional review board approval was obtained. RESULT(S): One hundred ninety-five patients (zuranolone, 98; placebo, 97) were randomized, received study drug, and had valid baseline and one or more post-baseline efficacy assessments. At day 15, patients receiving a 14-day treatment course of zuranolone showed nominally significant improvements across all HAMD-17 subscales versus placebo (least squares mean [SE] CFB treatment difference: Core Depression, 25.9 [2.4], P 5.0151; Anxiety, 25.7 [2.3], P 5.0123; Bech-6, 28.6 [3.0], P 5.0040; Maier, 27.6 [2.6], P 5.0041). Improvement in all subscales was observed starting at day 3. CONCLUSION(S): In SKYLARK, zuranolone was associated with rapid improvement in depressive and anxiety symptoms in patients with PPD across multiple domains, supporting its development as a potential oral, rapid-acting treatment option for PPD.

Deligiannidis, K., et al. (2021). "Rapid and Sustained Improvement in Concurrent Symptoms of Depression and Anxiety in a Post Hoc Analysis of Zuranolone Treatment in Postpartum Depression." Biological psychiatry 89(9): S157.
	Background: Zuranolone demonstrated improvements in depressive and anxiety symptoms versus placebo from a Phase 3 (NCT02978326; ROBIN) trial in postpartum depression (PPD). This post‐hoc analysis evaluated concurrent remission of depressive and anxiety symptoms. Methods: Women (n=151) ages 18‐45, ≤6 months postpartum, with PPD and Hamilton Rating Scale for Depression (HAMD‐17) total score ≥26, were randomized 1:1 to zuranolone 30mg or placebo for 2 weeks, with 4 weeks follow‐up. Change from baseline (CFB) in HAMD‐17 score (Day 15; primary endpoint), Montgomery‐Åsberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Anxiety (HAM‐A) were evaluated. Concurrent anxiety and depression remission were defined two ways: (1) HAMD‐17≤7+HAM‐A≤7, or (2) MADRS≤10+HAM‐A≤7. Sustained remission was defined as meeting concurrent remission criteria on both Day 15 and Day 45. Adjusted odds ratios were calculated using generalized estimating equation models. Results: Zuranolone demonstrated statistically significant Day 15 CFB versus placebo in HAMD‐17 total score (primary endpoint: ‐17.8 vs. ‐13.6, p=0.0028). A significantly higher proportion of zuranolone‐treated patients achieved concurrent remission of anxiety and depression (all p<0.05) as early as Day 3 and sustained remission on Days 15 and 45. The likelihood of achieving concurrent remission was significantly higher among zuranolone‐treated patients at Day 15 and Day 45 (odds range: 2.35–3.45 times higher versus placebo). Sustained remission was also significantly higher among zuranolone‐treated patients (odds range: 3.71–6.21). Conclusions: Zuranolone demonstrated rapid (Day 3) and sustained (Day 45) improvements in core depression symptoms, as well as sustained concurrent remission of depression and anxiety symptoms at Days 3, 15, and 45. Supported By: This study was sponsored by Sage Therapeutics, Inc. Keywords: Zuranolone, Postpartum Depression, Neuroactive Steroid, Anxiety, Sleep Disorder

Deligiannidis, K., et al. (2021). "Evaluation of Insomnia Symptoms in a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial of Zuranolone in Postpartum Depression." Biological psychiatry 89(9): S91.
	Background: Zuranolone is an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator with improvements in depressive and anxiety symptoms versus placebo from a Phase 3 (NCT02978326; ROBIN) trial in postpartum depression (PPD). This ROBIN trial post‐hoc analysis evaluated insomnia symptoms, a common comorbidity in PPD. Methods: Women (n=151) aged 18‐45 years, ≤6 months postpartum, with PPD (major depressive episode beginning in 3rd trimester or ≤4 weeks postpartum) and a 17‐Item Hamilton Rating Scale for Depression (HAMD‐17) total score ≥26, were randomized 1:1 to zuranolone 30 mg or placebo for 2 weeks, with 4 weeks follow‐up. Change from baseline (CFB) in HAMD‐17 total score (Day 15; primary endpoint) and the Montgomery‐Åsberg Depression Rating Scale (MADRS; secondary endpoint) were evaluated using a mixed‐effects model for repeated measures (MMRM). The HAMD‐17 insomnia subscale (HAMD‐17‐Ins) and MADRS individual insomnia item (MADRS‐Ins) scores were evaluated post‐hoc (not adjusted for multiplicity) using an MMRM. Results: Zuranolone demonstrated statistically significant Day 15 CFB versus placebo in HAMD‐17 total score (‐17.8 vs. ‐13.6, P=0.0028), MADRS (‐22.1 vs. ‐17.6, P=0.0180), and associated insomnia sub‐scales/items (difference zuranolone vs. placebo; HAMD‐17‐Ins: ‐1.003, P=0.0038; MADRS‐Ins: ‐0.773, P=0.0116). Significant CFB in insomnia sub‐scales/items favoring zuranolone were observed by Day 3 (HAMD‐17‐Ins: ‐0.841, P=0.0142; MADRS‐Ins: ‐0.710, P=0.017) and at Day 45 (HAMD‐17‐Ins: ‐0.730, P=0.0207; MADRS‐Ins: ‐0.636, P=0.0221). Most common (≥5%) adverse events were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. Conclusions: Zuranolone demonstrated rapid (Day 3) and sustained (Day 45) improvements in insomnia‐related symptoms compared with placebo. Funding Source: This study was sponsored by Sage Therapeutics, Inc. Keywords: Zuranolone, Postpartum Depression, Neuroactive Steroid, Insomnia, Sleep Disorder

Deligiannidis Kristina, M., et al. (2023). "Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression." The Journal of Clinical Psychiatry 84(1).
	Objective: Concurrent anxiety and/or insomnia symptoms in women with postpartum depression (PPD) are common and associated with more severe PPD. The effects of zuranolone on concurrent anxiety and/or insomnia symptoms and on patient-perceived functional health in women with PPD in the ROBIN study are reported.; Methods: The phase 3, double-blind, randomized, placebo-controlled trial (conducted January 2017-December 2018) included women aged 18-45 years, ≤ 6 months postpartum, with PPD (onset of DSM-5 -defined major depressive episode in the third trimester or ≤ 4 weeks postpartum) and baseline 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 26. Women were randomized 1:1 to once-daily oral zuranolone 30 mg (n = 77) or placebo (n = 76) for 14 days with follow-up through day 45. Concurrent remission of depressive and anxiety symptoms (Hamilton Anxiety Rating Scale total score ≤ 7 plus HDRS-17 total score ≤ 7 or Montgomery-Asberg Depression Rating Scale total score ≤ 10), improvement in insomnia symptoms, patient-perceived functional health, and treatment effect sizes described by number needed to treat (NNT) were assessed. Analyses were exploratory; P values are nominal.; Results: Rates of concurrent remission of depressive and anxiety symptoms were higher with zuranolone versus placebo (P < .05) at days 3, 15, and 45; the rate of sustained concurrent remission (ie, at both days 15 and 45) was also higher with zuranolone ( P < .05). Anxiety symptoms (assessed by HDRS-17 anxiety/somatization subscale and Edinburgh Postnatal Depression Scale anxiety subscale) improved with zuranolone versus placebo ( P < .05) at days 3 through 45. Potential benefits on insomnia symptoms and patient-perceived functional health were observed. Day 15 NNTs were 5 for both HDRS-17 response and remission.; Conclusions: Zuranolone was associated with concurrent improvements in depressive and anxiety symptoms, with beneficial effects on insomnia symptoms and patient-perceived functional health in adults with PPD.; Trial Registration: ClinicalTrials.gov identifier: NCT02978326. (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Deligiannidis Kristina, M., et al. (2022). "Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder with peripartum onset: A multicenter, open-label, controlled proof-of-concept clinical trial (DELOS-1)." Journal of Affective Disorders 316: 34-41.
	Background: Postpartum depression has a high prevalence in the United States (~13 %) and often goes undertreated/untreated. We conducted a multicenter, open-label, proof-of-concept trial to assess the Nēsos wearable, non-invasive, transcutaneous auricular vagus nerve stimulation (taVNS) system for the treatment of major depressive disorder with peripartum onset (PPD).; Methods: Women (n = 25), ages 18 to 45, within 9 months postpartum, and diagnosed with PPD were enrolled at 3 sites. The study included 6 weeks open-label therapy and 2 weeks observation. Efficacy outcomes included change from baseline (CFB) in Hamilton Rating Scale for Depression (HAMD17) total scores, HAM-D17 response and remission, and patient and clinician global impression of change (PGIC, CGIC) scores. Analysis included descriptive statistics and mixed-effects models for repeated measures.; Results: The most common AEs (≥5 %) were discomfort (n = 5), headache (n = 3), and dizziness (n = 2); all resolved without intervention. No serious AEs or deaths occurred. Baseline mean HAM-D17 score was 18.4. Week 6 least squares (LS) mean CFB in HAM-D17 score was -9.7; 74 % achieved response and 61 % achieved remission. At week 6, at least some improvement was reported by 21 of 22 (95 %) clinicians on CGIC and 22 of 23 (96 %) participants on PGIC.; Limitations: This was a single-arm, open-label study, and enrollment was limited to participants with mild-to-moderate peripartum depression.; Conclusion: Results from this proof-of-concept study suggest that the Nēsos taVNS system is well tolerated and may be an effective non-invasive, non-pharmacological treatment for major depressive disorder with peripartum onset. Further evaluation in larger sham-controlled studies is needed.; Clinicaltrials: govNCT03972995. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Della Corte, L., et al. (2023). "Is There Still a Place for Surgery in Patients with PCOS? A Review." Life (Basel, Switzerland) 13(6).
	OBJECTIVE: The surgical management of polycystic ovary syndrome (PCOS) represents an unclear option compared to medical therapy, and it is necessary to deepen the role of minimally invasive surgery, represented by laparoscopic ovarian drilling (LOD) and transvaginal hydrolaparoscopy (THL), for the treatment of PCOS in infertile women resistant to drug therapy and to establish its success in terms of ovulation and pregnancy rates. METHODS: A search was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and the Cochrane Library) from 1994 to October 2022 in order to evaluate the role of surgery in patients with PCOS resistant to pharmacological treatment. Only original scientific articles in English were included. RESULTS: Seventeen studies were analyzed in this review. In all analyzed studies, more than 50% of the population underwent spontaneous ovulation after surgical treatment without great differences between the two surgical techniques (LOD and THL). More than 40% of patients delivered, with a higher rate after LOD, although eight ectopic pregnancies and sixty-three miscarriages were reported. A lower risk of adhesion formation after THL has been reported. No clear data regarding the effect of surgery on the regularization of the menstrual cycle has been described. A reduction in LH and AMH serum levels as well as the LH/FSH ratio compared to preoperative levels for both surgical techniques has been described. CONCLUSIONS: Despite the scarcity and heterogeneity of data, surgical therapy could be considered an effective and safe approach in the management of PCOS patients with resistance to pharmacological treatment who desire to become pregnant.

Della Corte, L., et al. (2023). "Medical and Surgical Strategies in Vulvar Paget Disease: Let's Throw Some Light!" Journal of Personalized Medicine 13(1): 100.
	Background: Vulvar Paget's disease (VPD) is defined as a neoplasm of epithelial origin, mostly in postmenopausal women. Due to the extreme rarity of VPD, limited data about recommended treatment options are available. Surgical excision has been the treatment of choice although in the recent decade medical treatments have been proposed. Method(s): A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 2003 to September 2022, in order to analyze all medical and surgical strategies used for the treatment of VPD. Result(s): Thirty-four articles were included in this review with findings as follows: 390 patients were treated with medical or other conservative treatment while 2802 patients were treated surgically; 235/434 (54%) patients had a complete response, 67/434 (15%) a partial response, 10/434 (2.3%) a stable disease, 3/434 (0.7%) disease progress, 3/434 (0.7%) died of the disease, 55/434 (13%) died of other causes during follow up while 7/434 (1.6%) had to stop topical treatments with 5% imiquimod cream because of side effects; 239/434 patients (55%) had a recurrence and 11/434 (2.5%) were lost to follow-up. The length of follow-up was variable, according to the different studies analyzed. Conclusion(s): VPD is a chronic disease with a high recurrence rate and low mortality. There are no significant differences in recurrence rates in patients who undergo surgery and those who do not and the margin status at the time of primary surgery and recurrence. Several surgical and medical approaches providing both local control of the disease and minimal tissue damage have been developed. Clock mapping, a recent preoperative vulvo-vaginal workup tool, can predict the invasiveness and the extension of VPD. However, to date, due to the different treatment options available and in the absence of a global consensus, it is critical to tailor treatments to individual patient characteristics and biopsy histopathologic findings, to ensure the best type of therapy.Copyright © 2023 by the authors.

Della Corte, L., et al. (2023). "Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis." Journal of Clinical Medicine 12(22).
	Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis, and it holds promise as a therapeutic strategy, but its role remains elusive. The aim of this study was to assess the existing evidence for the use or not of HIPEC in primary debulking surgery (PDS), interval debulking surgery (IDS), and recurrent ovarian cancer (ROC), evaluated in terms of survival rates and post-surgical morbidity.; Methods: Medline, Pubmed, Cochrane, and Medscape were systematically searched for any article comparing the use of HIPEC treatment with any other therapy in patients with ovarian cancer in PDS, IDS, and ROC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. We only considered English-language published studies.; Results: We included 14 studies, including two RCTs with a total of 1813 women, published between 2003 and 2023 with a recruitment period between 1998 and 2020. In PDS, there were no differences in progression-free survival (PFS) between HIPEC and controls [MD -5.53 months [95% CI -19.91 to 8.84 months]; I 2 = 96%]. Conversely, in patients treated with NACT, pooled results showed a significant survival advantage in terms of progression-free survival (PFS) and overall survival (OS) in the combined HIPEC plus IDS group rather than surgery alone [PFS: MD 4.68 months (95% CI 3.49 to 5.86 months, I 2 = 95%); OS: MD 11.81 months (95% CI 9.34 to 14.27 months); I 2 = 97%]. Concerning ROC patients, pooled MD did not show either a significant PFS difference between intervention and controls [MD 2.68 months (95% CI 433 to 9.70 months); I 2 = 95%], and OS significant difference (MD 6.69 months [95% CI -9.09 to 22.47 months]; I 2 = 98%). Severe post-operative complications (≥grade 3) were available in 10 studies, accounting for 1108 women. Overall, there was a slightly but significantly increased risk with the combined approach compared to controls [RR 1.26 (95% CI 1.02 to 1.55); I 2 = 0%].; Conclusions: The combination of HIPEC with cytoreductive surgery prolongs OS and PFS in advanced epithelial ovarian cancer after NACT with acceptable morbidity. However, additional trials are still needed to determine the effectiveness of HIPEC in primary and recurrence settings. In the era of personalized medicine, the correlation between the efficacy of HIPEC and biological and molecular findings represents a challenge for the future of ovarian cancer.

Della Corte, L., et al. (2024). "The role of liquid biopsy in epithelial ovarian cancer: State of the art." Critical Reviews in Oncology/Hematology 194: 104263.
	The clinical implementation of liquid biopsy has dramatically modified the analytical paradigm for several solid tumors. To date, however, only circulating free DNA (cfDNA) has been approved in clinical practice to select targeted treatments for patients with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and breast cancer (BC). Interestingly, emerging liquid biopsy analytes in peripheral blood, including circulating tumor cells (CTC), miRNA, and extracellular vesicles (EVs), have been shown to play a crucial role in the clinical management of solid tumor patients. Here, we review how these blood-based biomarkers may positively impact early diagnosis, prognosis, and treatment response in ovarian cancer (OC) patients.Copyright © 2024 Elsevier B.V.

Dellino, M., et al. (2022). ""Intestinal-Type" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group." Cancers 14(20).
	Intestinal-type adenocarcinoma (VAIt) represents a sporadic variant of vulvar carcinoma. It appears frequently localized to epithelial glands in the vulvar region, and it probably derives from cloacal remnants persisting in the adult. We performed a systematic review of the limited cases reported in the literature, with the intent to assess the specific peculiarities of this rare neoplasia and to state consistent management recommendations. The principal histological VAIt characteristic is that it resembles mucinous colonic carcinomas. Therefore, immunohistochemical workup, with different tumor markers including CK20, CDX2, and CK7 staining, is needed. To confirm vulvar origin, a thorough diagnostic, and radiological examination is required to rule out other primary malignancies. The gold standard of treatment for VAIt is surgery, with local excision with tumor-free margins. Lymph node staging is an option advised if the tumor size is >2 cm or if lymph node metastases are suspected on imaging. On the other hand, the role of neoadjuvant therapy is still in doubt, but a good response to adjuvant chemotherapy treatments has been described in both advanced and recurrent diseases. Sometimes, VAIt behavior can be unpredictable, with relapses even after many years, so more experiences and longer follow-up periods are needed to elucidate the best therapeutic management and its long-term prognosis.

dell'Insubria Università degli, S. and d. Verona Universita (2022). Effects of Oral Inositol Supplementation on Obstetrics Outcomes in PCOS Women.
	No Results Available Dietary Supplement: Inositol + Folic acid|Dietary Supplement: Folic acid Gestational diabetes prevalence|Preeclampsia prevalence|Birth weight|Weight gain in pregnancy Female Not Applicable 80 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment IPOSI-1 December 31, 2026

Dell'Orto, F., et al. (2019). "Feasibility of sentinel lymph node mapping of the ovary: a systematic review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29(7): 1209-1215.
	Pelvic and para-aortic lymphadenectomy is routinely performed in early ovarian cancer to define the stage of the disease. However, it may be associated with increased blood loss, operative time, and length of hospitalization. The sentinel lymph node technique has been shown to be safe and feasible in vulvar, uterine, and cervical cancer. Data detailing feasibility and outcomes of sentinel lymph node mapping in ovarian cancer are scarce.To summarize the studies evaluating the feasibility of sentinel lymph node detection from the ovary, examining the technique and detection rate.A systematic search of the literature was performed using PubMed and Embase from June 1991 to February 2019. Studies describing the sentinel lymph node technique and lymphatic drainage of the ovaries were incorporated in this review. Ten articles were selected, comprising a total of 145 patients. A variety of agents were used, but the primary markers were technetium-99m radiocolloid (Tc-99m), patent blue, or indocyanine green, and the most common injection site was the ovarian ligaments.The overall sentinel lymph node detection rate was 90.3%.We propose a standardized technique sentinel lymph node mapping in ovarian cancer, using indocyanine green, or Tc-99m and blue dye as alternative tracers, injected in both the suspensory and the infundibulopelvic ligament of the ovary.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Delomenie, M., et al. (2019). "The clinical implication of lymph nodes micrometastases and isolated tumor cells in patients with cervical cancer: A systematic review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 241: 71-76.
	Lymph node macroscopic involvement in cervical cancer is a well-known prognostic factor, allows the gynecologic-oncologist to identify women at increased risk for recurrence. Since the development of sentinel node biopsy, micrometastases (MMs) and Isolated Tumor Cells (ICTs) have been increasingly identified in cervical cancer, however their prognostic value and treatment are still controversial. We reviewed the literature (MEDLINE and EMBASE database analysis) from inception up to January 2019, concerning the incidence of lymph nodes MMs and ITCs in cervical cancer, their controversial histologic and molecular biology definition, their anatomic distribution, the role of frozen section and the prognostic value and treatment options for women diagnosed with lymph nodes MMs/ITCs. (Copyright © 2019 Elsevier B.V. All rights reserved.)

DeMairo, J., et al. (2023). "Outcomes at the Motherhood Center: A Comparison of Virtual and On-Site Versions of a Specialized Perinatal Partial Hospitalization Program." Maternal and Child Health Journal.
	OBJECTIVES: Remotely administered mental health care is becoming increasingly common for treatment of a range of psychiatric disorders; however, there is a dearth of literature overviewing direct comparisons between remote and in-person interventions for treatment of Perinatal Mood and Anxiety Disorders (PMADs). The sudden advent of the Covid-19 pandemic in New York City forced an abrupt conversion for an intensive day treatment program for new mothers with PMADs, from an on-site to a remote program. METHODS: The current report compares outcomes of 81 women who completed the program in-person to those of 60 women who completed the program remotely. RESULTS: Improvement in depression scores was statistically superior in the remote program, and improvement in mother-infant bonding was statistically equivalent between the on-site and remote programs. DISCUSSION: These findings indicate that specialized partial hospitalization treatment for individuals with moderate to severe psychiatric illness can be effectively provided via telehealth, thus offering improved convenience, accessibility, and safety without compromising care. We conclude that remotely administered group psychotherapy is an effective intervention for women with moderate to severe PMADs.

Demian, G., et al. (2022). "Endometrial receptivity analysis (ERA) for a personalized embryo transfer (pET) in assisted reproductive technology: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Demir, E., et al. (2022). "Outcomes between non-IVF and IVF treatment after laparoscopic conservative surgery of advanced endometriosis with Endometriosis Fertility Index score >3." Medicine 101(37): e30602.
	Surgical excision of advanced endometriosis has been demonstrated to improve women's pain symptoms and quality of life in women in randomized placebo-controlled trials, but there is no strong evidence regarding the live birth rate. The revised American Fertility Society (r-AFS) classification for endometriosis has a limited predictive ability for fertility outcomes after surgery; therefore, EFI scoring has been advised for predicting conception after endometriosis surgery. No randomized controlled trials have investigated fertility outcomes in patients with advanced endometriosis after surgery. This study aimed to determine the outcomes of in vitro fertilization (IVF) or non-IVF treatments after conservative surgery for advanced endometriosis in patients with good prognosis Endometriosis Fertility Index (EFI) scores (>3). This prospective cohort study was conducted between April 2014 and April 2019 at a tertiary research hospital. In total, 113 women with suspected preoperative advanced endometriosis were enrolled in this study. A total of 90 women with advanced endometriosis underwent laparoscopic surgery. Fourteen patients with EFI score of ≤3 and 3 of them who had bilateral tubal occlusion were also excluded. Seventy-three women were included in this study. The remaining 30 women in the non-IVF group and 32 women in the IVF group were analyzed. The main outcome measures were cumulative pregnancy rates and live birth rates in both groups. Women who underwent IVF treatment were older than women (30 ± 3.41) who had non-IVF treatment (26.5 ± 3.07) after laparoscopic surgery (P < .001). The remaining baseline characteristics of the patients in both groups were similar. Clinical pregnancy, abortion, and live birth rates were similar in both the groups after 36 months of follow-up. This study demonstrated that cumulative pregnancy and live birth rates were similar to those of non-IVF or IVF treatments after conservative surgery for advanced endometriosis, if patients had good prognosis EFI scores. Furthermore, non-IVF treatments resulted in nearly the same clinical pregnancy results as IVF treatment within 1 year after surgery.; Competing Interests: The authors have no funding and conflicts of interests to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Demiralp, O., et al. (2023). "The effect of progressive muscle relaxation technique and myofascial release technique on premenstrual symptoms, blood circulation, and quality of life in women with premenstrual syndrome: A single-blind randomized controlled study." Medicine 102(27): e34223.
	Background: Premenstrual syndrome (PMS) is a common condition in women of reproductive age. It is characterized by a range of behavioral, physical, and psychological symptoms. The aim of this study is to investigate the effects of progressive relaxation and myofascial release technique (MRT) on premenstrual symptoms, blood flow rate, pain, sleep quality and quality of life, in women with PMS.; Method: The study will conduct as a single-blind randomized controlled trial. Study registered at the ClinicalTrial.gov Protocol ID: NCT05836454. The volunteers will be randomized using allocation software to be divided into 3 groups: the progressive muscle relaxation group, the MRT group, and the control group. Assessments will be conducted by another physical therapist who is blinded to the groups. The assessments will include the Premenstrual Syndrome Severity Score, Blood Flow Measurements, Short Form McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and Short Form-36 Health Survey.; Discussion: Since both methods provide relaxation, improve symptoms and quality of life, they have not been compared to each other in the literature. This prompt to us to plan this study.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Demuytere, J., et al. (2023). "The transcriptomic effects of hyperthermia in cisplatin HIPEC: results from the OVIP trial." European Journal of Surgical Oncology 49(2): e193.
	Background: HIPEC with cisplatin in addition to cytoreductive surgery (CRS) can be a valuable treatment option in stage III epithelial ovarian cancer. Some studies report hyperthermic enhancement of tumor cell killing for cisplatin in vitro and in murine models, and we previously reported a potentially enhanced pharmacokinetic profile of hyperthermic chemoperfusion when compared with normothermic chemoperfusion of cisplatin. However, there is only a very limited amount of human in vivo data on the effects of hyperthermic chemoperfusion on tumor cells. Here, we report a transcriptomic analysis of epithelial ovarian cancer peritoneal metastasis samples post-chemoperfusion of patients enrolled in the OvIP study (NCT02567253), a multicenter randomized trial investigating tumor tissue platinum penetration after normothermic (37degreeC) versus hyperthermic (41degreeC) chemoperfusion with cisplatin at 75 or 120 mg/m2. Material(s) and Method(s): CRS + HIPEC was performed utilizing an open coliseum technique. Patients were randomized to receive normothermic (37degreeC) or hyperthermic (41degreeC) chemoperfusion with cisplatin at 75 or 120 mg/m2 for 90 minutes. Following optimal cytoreduction, two parietal peritoneal index nodules were left during chemoperfusion, and resected for analysis after perfusion. Resected samples were kept in RNALater preservative medium following surgery, and frozen to -80 degrees. All samples were shipped to BGI technologies, Hong Kong, where RNA extraction and RNA-Seq (DNBSeq) was performed. Reads were aligned to GRCh38 using STAR and genes quantified using featureCounts. Differential gene expression was performed using DESeq2 followed by geneset enrichment analyses. Immune cell deconvolution was performed using CIBERSORT. Result(s): We analyzed post-perfusion samples from 37 patients. In accordance with previous in vitro data, hyperthermia induced a clear heat shock response when compared to normothermic chemoperfusion, exemplified by significant upregulation of HSPB1, also known as Hsp27. Additionally an upregulation of genes associated with poor prognosis in several cancers such as FXR1, HIST1H2BK, CKS2 and FKBP4 was observed. Pathways upregulated by hyperthermia included those linked to cisplatin response such as the E2F pathway and the G2M/DNA Damage checkpoints. Relatedly, we observed upregulation of both the mitotic spindle pathway and MTORC1 signaling, both known to be associated with cisplatin resistance. Immune cell deconvolution indiccated a temperature-specific depletion of CD8+ and CD4+ memory cells, with no dose effect. Other cell types were not significantly affected. Conclusion(s): Our results suggest a putative tumor-promoting transcriptomic response to hyperthermia of 41degreeC in ovarian cancer cells, in addition to a possible immune cell depleting effect. These effects potentially outweigh the earlier described in vitro and pharmacokinetic effects of hyperthermia, requiring further investigation.Copyright © 2022

Deng, H., et al. (2023). "Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 43(1): 2144177.
	This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I 2 = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I 2 = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I 2 = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I 2 = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I 2 = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENT What is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women. What do the results of this study add? This systematic review and meta-analysis of data from ten studies ( n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls. What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.

Deng, J., et al. (2020). "Chinese herbal medicine for previous cesarean scar defect: A protocol for systematic review and meta-analysis." Medicine 99(50): e23630.
	Background: Previous cesarean scar defect (PCSD) is a gynecological disease that can cause bleeding after intercourse, prolonging menstrual period, intermenstrual bleeding, dysmenorrhea, and even lead to infertility. Chinese herbal medicine plays an important role in the treatment of gynecological diseases in China and East Asia. This study aims to assess the efficacy and safety of Chinese herbal medicine for PCSD.; Methods: We search the following databases: PubMed, the Cochrane Library, Chinese Biomedical Literature Database (CB), Chinese Science and Technique Journals Database (VIP), EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and the Wanfang Database. Other sources will also be searched like Google Scholar and gray literature. All databases mentioned above are searched from the start date to the latest version. Randomized controlled trials will be included which recruiting PCSD participants to assess the efficacy and safety of Chinese herbal medicines against controls (placebo or other therapeutic agents). Primary outcomes will include the size of PCSD, menstrual cycle, menstrual phase, menstrual volume, duration of disease, security index. Two authors will independently scan the searched articles, extract the data from attached articles, and import them into Endnote X8 and use Microsoft Excel 2013 to manage data and information. We will assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the participation of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. The meta-analysis in this review will use RevMan 5.3 software.; Results: The study aims to evaluate the efficacy and safety of the treatment that Chinese herbal medicine for PCSD.; Conclusion: This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice.; Inplasy Registration Number: INPLASY202090080.

Deng, T. and Y. Dong (2023). "Effect of aerobic exercise on postoperative rehabilitation and life quality of patients with uterine leiomyoma." European Journal of Gynaecological Oncology 44(2): 130-131.
	Objectives: Uterine leiomyoma is a common benign tumor of women in clinical practice, which will cause a greater negative impact on the life quality of patients. Aerobic exercise can promote lung expansion and accelerate the recovery of the body. Therefore, this research explores the impact of aerobic exercise training on the postoperative rehabilitation and life quality of patients with uterine leiomyoma. Method(s): 88 patients with postoperative uterine leiomyoma admitted to our affiliated hospital from February 2021 to January 2022 were selected as the study subjects. The patients were randomly divided into observation group and control group, with 44 patients in each group. The patients in the observation group took appropriate aerobic exercise training, while the patients in the control group maintained routine treatment and nursing methods. Result(s): The postoperative rehabilitation of the two groups of patients is shown in Table 1. It can be seen that the time of getting out of bed, the first exhaust and the hospital stay in the observation group are shorter than those in the control group, and the difference is statistically significant (p < 0.05). The life quality of patients in the two groups is shown in Table 2. It can be found that the life quality scores in the observation group after aerobic exercise are higher than those in the control group, with a statistically significant difference (p < 0.05). Conclusion(s): The recovery effect of hysteromyoma after operation needs to be improved. Therefore, the effect of aerobic exercise on the postoperative rehabilitation and life quality of patients was explored. The results show that aerobic exercise training can effectively improve the life quality of patients, improve the postoperative rehabilitation effect, and has certain clinical application value..

Deng, T., et al. (2022). "Comparison of platinum monotherapy with concurrent chemoradiation therapy versus platinum-based dual drug therapy with concurrent chemoradiation therapy for locally advanced cervical cancer: a systematic review and meta-analysis." Infectious agents and cancer 17(1): 18.
	Objective: To compare the survival outcomes and adverse events of patients with locally advanced cervical cancer (LACC) who received platinum monotherapy with concurrent chemoradiation therapy (CCRT) versus platinum-based dual drug therapy with CCRT.; Method: All relevant literature was screened form the PubMed, EMBASE, Web of Science, The Cochrane Library and other databases from their establishment to October 2020. The main endpoint indicators included overall survival (OS) and progression-free survival (PFS). Grade 3 and above adverse events induced by chemotherapy were also compared.; Results: This study involved 17 literature and 4,106 patients. There were 2,066 patients treated with CCRT with platinum-based dual drug therapy and 2,040 patients received CCRT with platinum monotherapy. Meta-analysis results showed that, compared to CCRT with platinum monotherapy, OS (HR = 0.68, 95% CI 0.58-0.79) and PFS (HR = 0.67, 95% CI 0.58-0.77) of LACC patients were significantly improved by CCRT with platinum-based dual drug therapy. In addition, CCRT with platinum-based dual drug therapy led to more adverse reactions such as neutropenia (OR = 4.92, 95% CI 3.55-6.84), anemia (OR = 1.99, 95% CI 1.17-3.39), diarrhea (OR = 1.70, 95% CI 1.30-2.22), leukopenia (OR = 2.42, 95%CI 1.84-3.17), thrombocytopenia (OR = 2.87, 95%CI 1.44-5.72), etc. CONCLUSION: CCRT with platinum-based dual drug therapy improved OS and PFS of LACC patients relative to the CCRT with platinum monotherapy. But it also increased the adverse reactions caused by multiple chemotherapy drugs. Thus, it is crucial to select a proper chemotherapy regimen based on the actual tolerance of patients in clinical practice. (© 2022. The Author(s).)

Dengler, K. L., et al. (2021). "Preoperative pudendal block with liposomal and plain bupivacaine reduces pain associated with posterior colporrhaphy: a double-blinded, randomized controlled trial." American Journal of Obstetrics and Gynecology 225(5): 556.e551‐556.e510.
	Background: Pelvic reconstructive surgery may cause significant postoperative pain, especially with posterior colporrhaphy, contributing to a longer hospital stay and increased pain medication utilization. Regional blocks are being increasingly utilized in gynecologic surgery to improve postoperative pain and decrease opioid usage, yet preoperative pudendal blocks have not been used routinely during posterior colporrhaphy. Objective: This study aimed to compare the effect of preoperative regional pudendal nerve block using a combination of 1.3% liposomal and 0.25% plain bupivacaine vs 0.25% plain bupivacaine alone on vaginal pain after posterior colporrhaphy on postoperative days 1, 2, and 3. We hypothesized that there would be a reduction in vaginal pain scores for the study group vs the control group over the first 72 hours. Study Design: This was a double‐blinded, randomized controlled trial that included patients undergoing a posterior colporrhaphy, either independently or in conjunction with other vaginal or abdominal reconstructive procedures. Patients were block randomized to receive 20 mL of either a combination of 1.3% liposomal and 0.25% plain bupivacaine (study) or 20 mL of 0.25% plain bupivacaine (control) in a regional pudendal block before the start of surgery. Double blinding was achieved by covering four 5‐mL syringes containing the randomized local anesthetic. After induction of anesthesia, a pudendal nerve block was performed per standard technique (5 mL superiorly and 5 mL inferiorly each ischial spine) using a pudendal kit. The primary outcome was to evaluate postoperative vaginal pain using a visual analog scale on postoperative days 1, 2, and 3. Secondary outcomes included total analgesic medication usage through postoperative day 3, postoperative voiding and defecatory dysfunction, and impact of vaginal pain on quality of life factors. Results: A total of 120 patients were enrolled (60 in each group). There were no significant differences in demographic data, including baseline vaginal pain (P=.88). Postoperative vaginal pain scores were significantly lower in the combined liposomal and bupivacaine group at all time points vs the plain bupivacaine group. Median pain scores for the study and control groups, respectively, were 0 (0?2) and 2 (0?4) for postoperative day 1 (P=.03), 2 (1?4) and 3 (2?5) for postoperative day 2 (P=.05), and 2 (1?4) and 3 (2?5) for postoperative day 3 (P=.02). Vaginal pain scores increased from postoperative day 1 to postoperative days 2 and 3 in both groups. There was a significant decrease in ibuprofen (P=.01) and acetaminophen (P=.03) usage in the study group; however, there was no difference between groups in total opioid consumption through postoperative day 3 (P=.82). There was no difference in successful voiding trials (study 72%, control 82%, P=.30), return of bowel function (P>.99), or quality of life factors (sleep, stress, mood, and activity). Conclusion: Preoperative regional pudendal block with a combination of liposomal and plain bupivacaine provided more effective vaginal pain control than plain bupivacaine alone for reconstructive surgery that included posterior colporrhaphy. Given the statistically significant decrease in vaginal pain in the study group, this block may be considered as a potential adjunct for multimodal pain reduction in this patient population.

Denisiuk, P. and D. Rachon (2021). "Effects of 6 months treatment with different combined oral contraceptives on the selected metabolic parameters and markers of low-grade inflammation in women with polycystic ovary syndrome." European journal of translational and clinical medicine 4: 23.
	Introduction: Polycystic ovary syndrome (PCOS) apart from ovarian hyperandrogenism is also characterized by peripheral insulin resistance and hyperinsulinemia. The most common therapy of hyperandrogenism is combined oral contraceptive (COC) which apart from ethynylestradiol (EE) contain gestagens with anti‐androgenic properties. These in turn may also have unfavorable metabolic effects. Aim: The aim of study was to evaluate the effects of different COC on the selected metabolic parameters, hormones, lipid concentrations and markers of low grade inflammation (LGI). Subjects and methods: Sixty‐two women with PCOS (age range 17‐34 years) were randomly assigned to treatment with four COC preparations containing 20‐35 ug of EE and different types of progestins (2 mg of dienogest [DNG], 2 mg of cyproterone acetate [CPA], 250 ug of norgestimate [NGS] and 75 ug of gestodene [GSD]) for 6 months. Blood for the analyses was drawn at baseline and 6 months after intervention. Results: After 6 months the BMI, serum glucose, insulin and HOMA‐IR did not change in neither groups. Waist circumference was significantly lower with EE‐DNG (p < 0.05). Serum androgens and FAI decreased significantly in all the study groups (p < 0.05). Serum TSH concentrations increased only in the EE‐CPA group, as well as serum PRL (p < 0.05). Serum TCh increased significantly only in the EE‐DNG and EE‐CPA groups (p < 0.05). HDL‐Ch increased significantly in EE‐DNG, EE‐CPA and EE‐GSD (p < 0.05). Serum LDL‐Ch concentrations decreased significantly only in the EE‐DNG group (p = 0.011). Serum TG increased significantly in all the groups, as well as serum CRP (p < 0.05), whereas WBC increased significantly only in the EE‐NGS and EE‐GSD (p < 0.05). Conclusions: Six months treatment with studied COC do not have any significant effects on serum insulin, glucose and HOMA‐IR, but significantly increase serum TG, markers of LGI in women with PCOS. Some of them also increase serum HDL, TCh and reduce LDL‐Ch.

Dennis, C. L., et al. (2019). "Interventions (other than psychosocial, psychological and pharmacological) for treating postpartum depression." Cochrane Database of Systematic Reviews 2019(11): CD013460.
	This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. The primary objective of this review is to assess the effects, on mothers and families, of interventions (other than psychosocial, psychological and pharmacological) compared with usual care in postpartum depression. Secondary objectives are to examine the effectiveness of:. specific types of physical therapies (e.g. bright light therapy, physical exercise, yoga, acupuncture, sleep deprivation); specific types of nutraceuticals (e.g. omega-3 fatty acids); specific types of herbal remedies (e.g. St. John's Wort).Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Dennis, C. L., et al. (2020). "Psychosocial and psychological interventions for treating postpartum depression: An updated Cochrane systematic review." Arch. Women's Ment. Health 23(2): 238-None.
	
Dennis, N. and G. Hobson (2023). "Working well: Mitigating the impact of menopause in the workplace - A narrative evidence review." Maturitas 177: 107824.
	review was used to screen initial returns before a subsequent full-text review determined the final studies included. Result(s): Twelve studies were selected for in-depth review: four conducted in the UK, seven in continental Europe and one in South America. The findings of the papers fell into five categories: work ability, improved symptom management, mental wellbeing and empowerment, increased openness about menopause in the workplace, and the impact of management/leadership. None of the included interventions were reported to give a significant improvement in measures of work ability. However, there were improvements in women's wellbeing, and their ability to manage symptoms. Interventions to improve workplace openness and managers' skills were well received by participants. Conclusion(s): The evidence for effective workplace interventions for women experiencing menopause symptoms is currently lacking. There is considerable need for further high-quality evaluations of interventions designed to support women in the workplace.Copyright © 2023 The Authors

Denschlag, D., et al. (2021). "Impact of co-medication on survival in patients with ovarian cancer a analysis of 4 prospective trials of the ago-ovar and engot/ GCIG collaborators." International Journal of Gynecological Cancer 31(SUPPL 1): A214‐A215.
	Introduction/Background There is poor evidence from mostly retrospective series whether co‐medication with metformin, statin or beta‐blocker have an impact on survival in patients with primary ovarian cancer. The aim of this study was to investigate the association of these medications with survival. Methodology Individual data from 3 prospective phase III randomized controlled trials (AGO‐OVAR 11/ICON 7, 12, 16) and one phase II trial (AGO‐OVAR 15) were pooled and analyzed. Patients were either classified as ever‐user if the specific co‐medication was documented at least once during the trial. In. contrast, never‐users served as controls. Data were adjusted for potential confounders (age, FIGO stage, histology, residual tumor after surgery, ECOG performance status, BMI, Charlson Comorbidity Index and assigned treatment within the trial) in multivariate Cox regression analyses. Result(s) Overall, 2.857 patients were included in the analyses. Ever‐users were: N=100 patients received metformin (3.5%), N=226 received statins (7.9%), and N=475 (16.6%) received beta‐blockers (BB) (N=391 selective (sBB); N=84 non‐selective (nsBB)) as co‐medication. There were no significant differences regarding the baseline characteristics (histology, FIGO stage, residual tumor after surgery, and chemotherapy‐schedule) between ever‐ and neverusers except that ever‐users were significantly older and more obese, compared to controls. Median progression‐free (PFS) and overall survival (OS) for the entire cohort was 18.7 months and 60.1 months, respectively Multivariate analyses for PFS and OS including age, BMI, Histology, FIGO stage, residual tumor after surgery, ECOG performance status and CCI revealed neither a significant impact of metformin on survival of ever‐users, compared to never‐users (PFS HR 0.94 95%‐CI 0.69‐1.29, p=0.7; OS HR 0.82 95%‐CI 0.58‐1.17, p=0.28), nor for statins (PFS HR 0.98 95%‐CI 0.82‐1.18, p=0.87; OS HR 0.91 95%‐CI 0.74‐1.12, p=0.37), respectively. In contrast, ever‐users of sBB had a significantly elevated risk for recurrence and death in multivariate analysis (PFS HR 1.22 95%‐CI 1.05‐1.41, p=0.009; OS HR 1.25 95%‐CI 1.06‐1.47, p=0.009). Conclusion In this large pooled analysis neither a co‐medication with metformin nor with statins had a significant impact on survival in patients with primary ovarian cancer. In contrast, co‐medication with a beta‐blocker was associated with worse survival. Further studies are warranted to confirm this observation.

Denys, P., et al. (2023). "AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2)." Neurourology and Urodynamics 42(1): 153-167.
	Background: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. Objective(s): To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport; Ipsen Ltd.) according to etiology of NDOI. Design, Setting, and Participant(s): Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). Intervention(s): Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. Outcome Measurements and Statistical Analysis: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). Results and Limitations: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. Conclusion(s): AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. Patient Summary: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.Copyright © 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

Deodato, M., et al. (2023). "Efficacy of manual therapy and pelvic floor exercises for pain reduction in primary dysmenorrhea: A prospective observational study." Journal of Bodywork and Movement Therapies 36: 185-191.
	Background: Primary dysmenorrhea represents one of the most common causes of pelvic and low back pain. Pharmacological treatment can present some side effects, and non-pharmacological treatments should be considered to improve the symptoms of primary dysmenorrhea. The aim of this study was to evaluate the efficacy of manual therapy (MT), pelvic floor exercises (PFE), and their combination (MT + PFE) to improve clinical outcomes and pain sensitivity in women with primary dysmenorrhea. Method(s): A prospective observational study was conducted. Thirty females (age 25.0 +/- 6.1 y) with history of primary dysmenorrhea participated to 8 sessions of 60 min of either MT, PFE or MT + PFE, twice per week. They participated to the different treatments according to the different services offered by the school of physiotherapy. A 0-10 numeric rating scale (NRS) was administered to assess subjective pain, while short-form 36 (SF-36) was used to evaluate quality of life. The pressure pain threshold (PPT) was assessed with a portable algometer on different pelvic and lumbar areas. Result(s): Independently from the treatment, significant improvements were reported for general pain NRS (p < 0.001; peta2 = 0.511), as well as most the domains of the SF-36, although the general health domain did not reach statistical significance (p = 0.613; peta2 = 0.010). PPT revealed a general improvement in all tested body areas, although on the quadratus lumborum, the PFE treatment did not induce a significant improvement compared to the MT and MT + PFE protocols (p = 0.039). Conclusion(s): These findings highlight the importance of proposing physiotherapy treatments to females with primary dysmenorrhea to improve symptoms, with manual therapy combined with active pelvic floor exercise providing the best outcomes including an improvement of lumbar pain thresholds.Copyright © 2023 Elsevier Ltd

Derby University, o. (2021). Developing an Evidence Base for the Use of Art Psychotherapy Within a Perinatal Mental Health Service.
	No Results Available Behavioral: Art Psychotherapy, Art Therapy|Behavioral: Wait List Measure any changes in mental wellbeing during the term of the Art Therapy intervention.|Monitor patient reported quality of life during the term of the Art Therapy intervention.|Monitor patient reported quality of life during the term of the Art Therapy intervention and during the wait-list period.|Monitor changes in mother-infant interaction during the term of the Art Therapy intervention and during the wait-list period.|Statistical analysis of change in mental wellbeing as assessed by the use of Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)|Statistical analysis of change in patient reported quality of life as assessed by the use of ReQol20 (Recovering Quality of Life)|Statistical analysis of change in patient reported quality of life as assessed by the use of ReQol10 (Recovering Quality of Life)|Statistical analysis of changes in mother-infant interaction as assessed by the use of the Bethlem Mother-Infant Interaction Scale.|Capture the participants lived experience of Art Therapy|Measure participant interaction with art materials during Art Therapy intervention Female Not Applicable 8 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Stanhope 100491262 May 26, 2022

Dermofarm, S. A. U. (2023). Efficacy and Safety of a Hyaluronic Acid-Based Vaginal Moisturizer Medical Device to Ease Symptoms of Vaginal Dryness.
	No Results Available Device: Hidrante HA|Device: Cumlaude Hidrante Interno® Vaginal Health Index|Severity of subjective symptoms (investigator record)|Subjective symtomps (patient's notebook)|Objective signs of vulvovaginal atrophy|Vaginal pH|Sexual function|Global Symptom Score (GSS)|Adverse events as a measure of Safety and Tolerability|Overall Safety Assessment|Patient satisfaction Female Not Applicable 54 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment DFARM-HYDRA-HA-2022 October 18, 2023

Desaunay, P., et al. (2023). "Benefits and Risks of Antidepressant Drugs During Pregnancy: A Systematic Review of Meta-analyses." Paediatric drugs 25(3): 247-265.
	Background: The prescription of antidepressant drugs during pregnancy has been steadily increasing for several decades. Meta-analyses (MAs), which increase the statistical power and precision of results, have gained interest for assessing the safety of antidepressant drugs during pregnancy.; Objective: We aimed to provide a meta-review of MAs assessing the benefits and risks of antidepressant drug use during pregnancy.; Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search on PubMed and Web of Science databases was conducted on 25 October, 2021, on MAs assessing the association between antidepressant drug use during pregnancy and health outcomes for the pregnant women, embryo, fetus, newborn, and developing child. Study selection and data extraction were carried out independently and in duplicate by two authors. The methodological quality of included studies was evaluated with the AMSTAR-2 tool. Overlap among MAs was assessed by calculating the corrected covered area. Data were presented in a narrative synthesis, using four levels of evidence.; Results: Fifty-one MAs were included, all but one assessing risks. These provided evidence for a significant increase in the risks for major congenital malformations (selective serotonin reuptake inhibitors, paroxetine, fluoxetine, no evidence for sertraline; eight MAs), congenital heart defects (paroxetine, fluoxetine, sertraline; 11 MAs), preterm birth (eight MAs), neonatal adaptation symptoms (eight MAs), and persistent pulmonary hypertension of the newborn (three MAs). There was limited evidence (only one MA for each outcome) for a significant increase in the risks for postpartum hemorrhage, and with a high risk of bias, for stillbirth, impaired motor development, and intellectual disability. There was inconclusive evidence, i.e., discrepant results, for an increase in the risks for spontaneous abortion, small for gestational age and low birthweight, respiratory distress, convulsions, feeding problems, and for a subsequent risk for autism with an early antidepressant drug exposure. Finally, MAs provided no evidence for an increase in the risks for gestational hypertension, preeclampsia, and for a subsequent risk for attention-deficit/hyperactivity disorder. Only one MA assessed benefits, providing limited evidence for preventing relapse in severe or recurrent depression. Effect sizes were small, except for neonatal symptoms (small to large). Results were based on MAs in which overall methodological quality was low (AMSTAR-2 score = 54.8% ± 12.9%, [19-81%]), with a high risk of bias, notably indication bias. The corrected covered area was 3.27%, which corresponds to a slight overlap.; Conclusions: This meta-review has implications for clinical practice and future research. First, these results suggest that antidepressant drugs should be used as a second-line treatment during pregnancy (after first-line psychotherapy, according to the guidelines). The risk of major congenital malformations could be prevented by observing guidelines that discourage the use of paroxetine and fluoxetine. Second, to decrease heterogeneity and bias, future MAs should adjust for maternal psychiatric disorders and antidepressant drug dosage, and perform analyses by timing of exposure. (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Deswal, R., et al. (2019). "Single nucleotide polymorphisms in treatment of polycystic ovary syndrome: a systematic review." Drug metabolism reviews 51(4): 612-622.
	As 15-20% of reproductive aged females are suffering from polycystic ovary syndrome (PCOS), a large number of pharmacological preparations are frequently available in the market for the treatment of PCOS; however, they seem to be ineffective and cause undesirable side effects. This has emphasized the need to optimize dosage regimens for individualized treatment. The objective of this systematic review is to review single nucleotide polymorphisms (SNPs) associated with drugs used for the treatment of PCOS to understand pharmacogenetics variability of patients to drug response there by helping clinicians in designing tailored treatments and possibly reducing adverse drug reactions. A comprehensive electronic literature search was conducted to highlight some clinically relevant SNPs that act to influence PCOS and associated co-morbidities. A total of 16 studies were included in this review. These genetic variations can be used as a potential target for pharmacotherapy and pharmacogenetic clinical trials for better diagnosis, management, and treatment planning.

Devi, N., et al. (2020). "N -acetyl-cysteine as adjuvant therapy in female infertility: a systematic review and meta-analysis." Journal of basic and clinical physiology and pharmacology 32(5): 899-910.
	Objectives: The objective of this study is to explore the efficacy and safety of N -acetyl-cysteine (NAC) as adjuvant therapy in female infertility.; Content: We performed a systematic literature search of PubMed, Cochrane Library, Embase, and Ovid databases through April 2019 for Randomized Controlled Trials (RCTs) evaluating the effectiveness and safety of NAC as adjuvant therapy in female infertility. The outcomes assessed were rates of ovulation, pregnancy, miscarriage and multiple pregnancy, presented as pooled odds ratio with 95% confidence interval (CI) using the random-effects model. Heterogeneity and inconsistency of the measurements were identified through Cochrane's Q statistic and I2 statistic. We also performed a sensitivity analysis, publication bias (using funnel plot and Begg's test), and subgroup analysis.; Summary: Fifteen RCTs recruiting 2330 female receiving NAC were included. The pooled estimate showed the statistically insignificant improvement in outcomes; clinical pregnancy rate 1.55 (95% CI 0.98-2.47; I2=68%; p<0.01), ovulation rate 1.77 (95% CI 0.76-4.14; I2=90%; p<0.01), multiple pregnancy rate 0.83 (95% CI 0.34-1.99; I2=10%; p=0.31) and miscarriage rate 0.76 (95% CI= 0.37, 1.53; I2=0%; p=0.69) . NAC was found less efficacious and safe than metformin in all outcomes. Overall, NAC showed statistically insignificant (OR=0.98-2.47).; Outlook: NAC can be an effective adjuvant in PCOS related and unexplained female infertility. The effect could be more profound in women with high BMI, insulin resistance, and oxidative stress. However, the findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in more extended follow-up periods. (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Dewald Cornelia Lieselotte, A., et al. (2024). "Interventional Therapy of Pelvic Venous Disorders (PeVD)." RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.
	Background: Pelvic venous disorders (PeVD) are an underdiagnosed cause of chronic pelvic pain in women. They are caused by venous insufficiency of the pelvic or ovarian veins, leading to the development of mainly periuterine and periovarian varices. It is a progressive disease if left untreated and can cause swelling, dyspareunia, dysmenorrhea, and other symptoms, some non-specific, that affect the patient's quality of life. Interventional therapies are a central component of the treatment of PeVD, with a variety of techniques available for both diagnosis and treatment.; Method: This review provides an overview of the pathophysiologic background, diagnosis, and, most importantly, interventional treatment options for PeVD.; Results: There is a lack of standardized nomenclature and internationally accepted diagnostic criteria for PeVD as well as randomized controlled trials demonstrating clinical success. However, in clinical trials, endovascular therapy for PeVD has been shown to be safe and effective. This review presents the various interventional techniques for the treatment of PeVD, including embolization, stenting, and sclerotherapy.; Conclusion: The importance of PeVD is receiving growing recognition. Recent advances, such as the development of the Symptoms-Varices-Pathophysiology (SVP) classification, provide an impetus to standardize nomenclature and are the first step toward systematizing disease management. Interventional therapies provide a safe and tailored minimally invasive treatment option for patients with PeVD.; Key Points: · Pelvic venous disorders are an underdiagnosed condition with frequently delayed diagnosis and debilitating symptoms.. · Until now, the PeVD nomenclature has been imprecise, with terms like May-Thurner syndrome/Nutcracker syndrome.. · Interventional approaches are effective and play a central role in PeVD treatment..; Citation Format: · Dewald CL, Becker LS, Meyer BC. Interventional Therapy of Pelvic Venous Disorders (PeVD). Fortschr Röntgenstr 2024; DOI: 10.1055/a-2229-4100.; Competing Interests: The authors declare that they have no conflict of interest. (Thieme. All rights reserved.)

Dhanis, J., et al. (2022). "Prehabilitation to Improve Outcomes of Patients with Gynaecological Cancer: A New Window of Opportunity?" Cancers 14(14): 3448.
	The literature evaluating the effect of prehabilitation programmes on postoperative outcomes and quality of life of patients with gynaecological cancer undergoing surgery was reviewed. Databases including Pubmed, Medline, EMBASE (Ovid) and PsycINFO were systematically searched to identify studies evaluating the effect of prehabilitation programmes on patients with gynaecological cancer. Both unimodal and multimodal prehabilitation programmes were included encompassing physical exercise and nutritional and psychological support. Primary outcomes were surgical complications and quality of life. Secondary outcomes were anthropometric changes and adherence to the prehabilitation programme. Seven studies fulfilled the inclusion criteria, comprising 580 patients. Included studies were nonrandomised prospective studies (n = 4), retrospective studies (n = 2) and one case report. Unimodal programmes and multimodal programmes were included. In patients with ovarian cancer, multimodal prehabilitation resulted in significantly reduced hospital stay and time to chemotherapy. In patients with endometrial and cervical cancer, prehabilitation was associated with significant weight loss, but had no significant effects on surgical complications or mortality. No adverse events of the programmes were reported. Evidence on the effect of prehabilitation for patients with gynaecological cancer is limited. Future studies are needed to determine the effects on postoperative complications and quality of life.Copyright © 2022 by the authors.

Dhatt, A., et al. (2022). "Fertility outcomes following treatment of chronic endometritis: a systematic review and meta-analysis." Human Reproduction 37(Supplement 1): i394.
	Study question: To determine if treatment of chronic endometritis (CE) impacts fertility outcomes Summary answer: Treatment of CE in women with infertility, recurrent pregnancy loss, or recurrent implantation failure, improves live birth outcomes What is known already: Chronic endometritis is an inflammatory condition that involves plasma cells invading the endometrial stroma. Prevalence of CE is high among patients with recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and infertility. Proposed treatment strategies include oral antibiotics, intrauterine antibiotic infusion, platelet-rich plasma, and hysteroscopic surgery, among others. Although treatment-associated CE cure rates have been high, few studies have reported on fertility outcomes following treatment of CE. Previously published systematic reviews have also yielded widely conflicting outcomes regarding the impact of CE treatment on fertility outcomes. Study design, size, duration: We conducted a systematic search of the literature until late December 2021 across the Cochrane, EMBASE, and Medline databases. We used a DerSimonian and Laird random-effects metaanalysis model for the quantitative analysis. Participants/materials, setting, methods: Clinical trials, prospective and retrospective observational studies that examined the treatment outcomes of CE were included. Study eligibility assessment, data extraction, and risk of bias assessment were independently performed by two reviewers. Comparisons were made between the groups of treated versus untreated CE, treated versus persistent CE, and between specific treatment strategies. Pooled risk ratios (RR) for the impact of CE treatment on outcomes such as live birth, clinical pregnancy, and miscarriage rates were assessed Main results and the role of chance: Twelve studies totalling 1,539 women were included in our systematic review(3 randomized controlled trials and 9 observational studies), and 5 studies were included in the quantitative meta-analysis. Patients all had confirmed CE and a history of infertility, RPL, or RIF. Cure rates ranged between 37.2-91.8%. Live birth rate in the treated CE group ranged from 27.1-84.6%, from 16.4-44.4% in the nontreated CE group, and from 6.7-30.8% in the persistent CE group. Clinical pregnancy rate in the treated CE group ranged from 29.3-76.3%, from 11.1- 30% in the non-treated CE group, and from 20-42.3% in the persistent CE group. Miscarriage rate in the treated CE group ranged from 6.7-23.8%, from 35.7-55.6% in the non-treated CE group, and from 27.3-66.7% in the persistent CE group. Risk ratio for the pooled effect of successful CE treatment compared to persistent CE on live birth was 2.98 (95% confidence ratio [CI] 1.51-5.91, I2=36.8%), on clinical pregnancy rate was 2.25 (95% CI 1.59-3.18, I2=40.1%), and on miscarriage rate was 0.55 (95% CI 0.28-1.10, I2=0.0%). Insufficient studies compared specific treatment subtypes to allow for any substantive qualitative or quantitative analysis. Limitations, reasons for caution: Our results are limited by significant between- study heterogeneity in the study design, patient population, and comparisons used. Subgroup analysis by categories of comparisons mitigates some of this heterogeneity Wider implications of the findings: Adequate treatment of CE significantly improves live birth rates in patients with RPL, RIF, and infertility. Assessment for CE should become part of routine fertility investigations, and resolution of CE must be confirmed prior to initiating fertility treatments.

Dholakia, J., et al. (2021). "Prehabilitation for medically frail patients undergoing surgery for epithelial ovarian cancer: a cost-effectiveness analysis." Journal of Gynecologic Oncology 32(6): e92.
	Objective: To assess the potential cost-effectiveness of prehabilitation in medically frail patients undergoing surgery for epithelial ovarian cancer (EOC). Method(s): We created a cost-effectiveness model evaluating the impact of prehabilitation on a cohort of medically frail women undergoing primary surgical intervention for EOC. Cost was assessed from the healthcare system perspective via (1) inpatient charges from 2018-2019 institutional Diagnostic Related Grouping data for surgeries with and without major complications; (2) nursing facility costs from published market surveys. Major complication and non-home discharge rates were estimated from the literature. Based on published pilot studies, prehabilitation was determined to decrease these rates. Incremental cost-effectiveness ratio for cost per life year saved utilized a willingness-to-pay threshold of $100,000/life year. Modeling was performed with TreeAge software. Result(s): In a cohort of 4,415 women, prehabilitation would cost $371.1 Million (M) versus $404.9 M for usual care, a cost saving of $33.8 M/year. Cost of care per patient with prehabilitation was $84,053; usual care was $91,713. When analyzed for cost-effectiveness, usual care was dominated by prehabilitation, indicating prehabilitation was associated with both increased effectiveness and decreased cost compared with usual care. Sensitivity analysis showed prehabilitation was more cost effective up to a cost of intervention of $9,418/patient. Conclusion(s): Prehabilitation appears to be a cost-saving method to decrease healthcare system costs via two improved outcomes: lower complication rates and decreased care facility requirements. It represents a novel strategy to optimize healthcare efficiency. Prospective studies should be performed to better characterize these interventions in medically frail patients with EOC.Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Di Biase, N., et al. (2019). "Review of general suggestions on physical activity to prevent and treat gestational and pre-existing diabetes during pregnancy and in postpartum." Nutrition, Metabolism and Cardiovascular Diseases 29(2): 115-126.
	The aim of this review is to provide general suggestions on physical activity (PA) in pre-gestational and gestational diabetes mellitus (GDM) and encourage women to take part in safe and effective activities throughout pregnancy, in the absence of other contraindications. PA before and during pregnancy and in postpartum has many positive effects on the mother, as it could reduce the risk of GDM, excessive weight gain and lower back pain and also prevents, in the postpartum, diabetes mellitus. It may also reduce the duration of labour and complications at childbirth, fatigue, stress, anxiety and depression, thereby leading to an improved sense of wellbeing. Clinically, it is thought to help prevent preeclampsia and premature birth even though RCTs provide conflicting evidence with regard to the prevention of GDM. The main reason for this rests on the fact that the majority of clinical trials have not been able to replicate the preventive effect of PA on the onset of GDM, such as the different adherence of the patient to PA. Herein, we survey the literature regarding exercise and PA on GDM prevention and treatment as well as on clinical outcomes in pre-GDM in pregnancy. On the basis of the current literature, we also present a series of general recommendations and suggestions on PA and exercise training in pregnancy among both diabetic patients and those at risk for GDM.Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

Di Donato, V., et al. (2020). "Management of morbidity associated with pancreatic resection during cytoreductive surgery for epithelial ovarian cancer: A systematic review." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 46(4 Pt A): 694-702.
	Introduction: In ovarian cancer (OC), survival benefit in case of complete cytoreduction with absence of residual tumor has been clearly demonstrated; however, it often requires extensive surgery. Particularly, pancreatic resection during cytoreduction, may severely impact perioperative morbidity and mortality.; Objectives: The aim of this systematic review is to evaluate complication rates and related optimal management of ovarian cancer patients undergoing pancreatic resection as part of cytoreductive surgery.; Methods: Literature was searched for relevant records reporting distal pancreatectomy for advanced ovarian cancer. All cohorts were rated for quality. We focused our analysis on complications related to pancreatic surgical procedures evaluating the following outcomes: pancreatic fistula (PF), abdominal abscess, pancreatitis, iatrogenic diabetes, hemorrhage from splenic vessels and pancreatic-surgery-related mortality.; Results: The most frequent complication reported was PF. Similar rates of PF were reported after hand-sewn (20%) or stapled closure (24%). Continued drainage is the standard treatment, and often, the leak can be managed conservatively and does not require re-intervention. Abdominal abscess is the second most frequent complication and generally follows a non-adequately drained PF and often required re-laparotomy. Pancreatitis is a rare event that could be treated conservatively; however, death can occur in case of necrotic evolution. Cases of post-operative hemorrhage due to splenic vessel bleeding have been described and represent an emergency.; Conclusions: Knowledge of pancreatic surgery and management of possible complications ought to be present in the oncologic-gynecologic armamentarium. All patients should be referred to specialized, dedicated, tertiary centers in order to reduce, promptly recognize and optimally manage complications.; Competing Interests: Declaration of competing interest The authors declare no conflict of interest. (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Di Donato, V., et al. (2022). "HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis." Vaccines 10(2): 239.
	Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites. Method(s): A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Result(s): Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia (p = 0.005) and recurrent respiratory papillomatosis (p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals. Conclusion(s): Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment.Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Di Donato, V., et al. (2021). "Preoperative frailty assessment in patients undergoing gynecologic oncology surgery: A systematic review." Gynecologic Oncology 161(1): 11-19.
	Objective: The aim of the present article was to discuss currently available evidence on the impact of frailty assessment on adverse postoperative outcomes and survival in patients undergoing surgery for gynecological cancer.; Methods: Systematic search of Medline (PubMed) and Embase databases until September 30, 2020. Key inclusion criteria were: (1) randomized or observational studies; (2) patients undergoing non-emergent surgery for gynecological malignancies; (3) preoperative frailty assessment.; Results: Through the process of evidence acquisition, twelve studies including 85,672 patients were selected and six tools were evaluable: 30-item frailty index, 40-item frailty index, modified frailty index (mFI), John Hopkins Adjusted Clinical Groups index, Fried frailty criteria, Driver's tool. The prevalence of frailty varied roughly from 6.1% to 60% across different series included. The mFI was the most adopted and predictive instrument. Pooled results underlined that frail patients were more likely to develop 30-day postoperative complications (OR:4.16; 95%CI 1.49-11.65; p:0.007), non-home discharge (OR:4.41; 95%CI: 4.09-4.76; p < 0.001), ICU admission (OR:3.99;3.76-4.24; p < 0.001) than the non-frail counterpart. Additionally, frail patients experienced worse oncologic outcomes (disease-free and overall survivals) than non-frail patients.; Conclusion: The present systematic review demonstrated that preoperative frailty assessment among gynecologic oncology patients is essential to predict adverse outcomes and tailor a personalized treatment. The mFI appeared as the most used and feasible tool in daily practice, suggesting that tailored therapeutic strategies should be considered for patients with 3 or more frailty-defining items.; Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflict of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Di Donato, V., et al. (2021). "Adjuvant hpv vaccination to prevent recurrent cervical dysplasia after surgical treatment: A meta-analysis." Vaccines 9(5): 410.
	Objective: The aim of this meta-analysis was to discuss evidence supporting the efficacy of adjuvant human papillomavirus (HPV) vaccination in reducing the risk of recurrent cervical intraepithelial neoplasia (CIN) 2 or greater after surgical treatment. Method(s): A systematic literature search was performed for studies reporting the impact of HPV vaccination on reducing the risk of recurrence of CIN 2+ after surgical excision. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Result(s): Eleven studies met the inclusion criteria and were selected for analysis. In total, 21,310 patients were included: 4039 (19%) received peri-operational adjuvant HPV vaccination while 17,271 (81%) received surgery alone. The recurrence of CIN 2+ after treatment was significantly lower in the vaccinated compared with the unvaccinated group (OR 0.35; 95% CI 0.21-0.56; p < 0.0001). The recurrence of CIN 1+ after treatment was significantly lower in the vaccinated compared with the unvaccinated group (OR 0.51; 95% CI 0.31-0.83; p = 0.006). A non-significant trend of reduction rate of HPV persistence was observed in the vaccinated compared with the unvaccinated cohorts (OR was 0.84; 95% CI 0.61-1.15; p = 0.28). Conclusion(s): HPV vaccination, in adjuvant setting, is associated with a reduced risk of recurrent CIN 1+ and CIN 2+ after surgical treatment.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Di Donato, V., et al. (2021). "Fertility-sparing surgery for women with stage I cervical cancer of 4 cm or larger: a systematic review." Journal of Gynecologic Oncology 32(6): e83.
	Objective: To investigate current evidence on oncological, fertility and obstetric outcomes of patients with stage I cervical cancer of 4 cm or larger undergoing fertility-sparing surgery (FSS).; Methods: Systematic review of studies including women affected by stage I cervical cancer ≥4 cm who underwent FSS. Main outcome measures: disease-free survival (DFS), overall survival (OS), pregnancy rate, live birth rate, premature delivery rate.; Results: Fifteen studies met all eligibility criteria for this systematic review, involving 48 patients affected by cervical cancer ≥4 cm who completed FSS. Three patients (6.3%) experienced a recurrence and one of them (2.1%) died of disease. The 5-year DFS rate was 92.4%. The 5-year OS rate was 97.6%. A significantly shorter 5-year DFS was reported for high-risk patients (G3, non-squamous histotype, diameter ≥5 cm) compared with low-risk (74.7% vs. 100%; log-rank test, p=0.024). Data about fertility outcomes were available for 12 patients. Five patients out of 12 (41.7%) attempted to conceive with an estimated pregnancy rate of 80%, a live birth rate of 83.3% and a premature delivery rate of 20%.; Conclusion: Women with high tumor grade, aggressive histology and tumor size ≥5 cm have a higher risk of recurrence. Oncologic outcomes are encouraging among low-risk patients; however, the lack of high-quality studies makes it difficult to draw any firm conclusions. Prospective multicentric clinical trials with a proper selection of inclusion/exclusion criteria should be conducted in women with low-risk factors, strong desire to preserve their fertility and high likelihood to conceive.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Di Donato, V., et al. (2019). "Uterine asymptomatic myomas: An overview from diagnosis to treatment." Giornale Italiano di Ostetricia e Ginecologia 41(2): 76-83.
	Objective. Uterine myomas represent the most common benign gynecological tumors and about 40-60% of patients with fibroids are asymptomatic. The diagnosis is often incidental and the treatment depends on patient's age, size of fibroids, estimated rate of growth, woman's fertility plans and risk of malignancy. Despite the prevalence, scientific research regarding asymptomatic fibroids is still underfunded compared with other nonmalignant diseases and actually, no guidelines are reported about management and treatment of themselves. Material and method We conducted a review of literature from February to May 2017. PubMed (MEDLINE), Web of Science databases, EMBASE, Cochrane Library and Scopus database were systematically searched for records reporting on asymptomatic fibroids. Results. Further large studies are needed to define the management of asymptomatic fibroids, real indications to treatment and risks and benefits of a waiting strategy when no treatment is needed can be drawn. Conclusion. No standard guidelines for the management of asymptomatic fibroids have been reported. Treatment is individualized and depends on patient s age, size of fibroids, woman s fertility plans and risk of malignancy.© Copyright 2019, CIC Edizioni Internazionali, Roma.

Di Donato, V., et al. (2020). "Does Hormone Replacement Therapy Impact the Prognosis in Endometrial Cancer Survivors? A Systematic Review." Oncology 98(4): 195-201.
	Purpose: The objective of this study was to evaluate the impact of hormone replacement therapy (HRT) on the prognosis in endometrial cancer (EC) survivors.; Methods: The research was conducted using the following electronic databases: MEDLINE (PubMed), Web of Science, ClinicalTrial.gov, and Cochrane Library. We performed a review of studies published from January 1986 to January 2019. We selected studies that included EC patients submitted to surgery with curative intent and postoperative use of HRT.; Result: Seven of 1,332 abstracts considered were eligible: 4 retrospective series, 1 prospective study, 1 randomized controlled trial, and 1 population study. Globally in the observed studies there was not a significant increase in the recurrence rate, measured by the relative risk, in the EC survivors using HRT compared with the controls in tumour stages I and II. The bias was that HRT was prescribed only to low-risk patients, who were young and had a low stage of disease.; Conclusion: This systematic review shows that HRT use had no negative effect on prognosis in EC survivors in tumour stages I and II. (© 2020 S. Karger AG, Basel.)

Di Donna Mariano, C., et al. (2022). "Conventional Laparoscopy versus Robotic-Assisted Aortic Lymph-Nodal Staging for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 11(12).
	Aortic lymph node metastases are a relative common finding in locally advanced cervical cancer. Minimally invasive surgery is the preferred approach to perform para-aortic lymph nodal staging to reduce complications, hospital stay, and the time to primary treatment. This meta-analysis (CRD42022335095) aimed to compare the surgical outcomes of the two most advanced approaches for the aortic staging procedure: conventional laparoscopy (CL) versus robotic-assisted laparoscopy (RAL). The meta-analysis was conducted according to the PRISMA guideline. The search string included the following keywords: "Laparoscopy" (MeSH Unique ID: D010535), "Robotic Surgical Procedures" (MeSH Unique ID: D065287), "Lymph Node Excision" (MeSH Unique ID: D008197) and "Aorta" (MeSH Unique ID: D001011), and "Uterine Cervical Neoplasms" (MeSH Unique ID: D002583). A total of 1324 patients were included in the analysis. Overall, 1200 patients were included in the CL group and 124 patients in the RAL group. Estimated blood loss was significantly higher in CL compared with RAL ( p = 0.02), whereas hospital stay was longer in RAL compared with CL ( p = 0.02). We did not find significant difference for all the other parameters, including operative time, intra- and postoperative complication rate, and number of lymph nodes excised. Based on our data analysis, both CL and RAL are valid options for para-aortic staging lymphadenectomy in locally advanced cervical cancer.

Di Donna Mariano, C., et al. (2023). "Detection of sentinel lymph node in vulvar cancer using 99m Tc-labeled colloid lymphoscintigraphy, blue dye, and indocyanine-green fluorescence: a meta-analysis of studies published in 2010-2020." Archives of Gynecology and Obstetrics 307(6): 1677-1686.
	Objectives: Sentinel lymph node (SLN) biopsy is widely accepted in the surgical staging of early vulvar cancer, although the most accurate method for its identification is not yet defined. This meta-analysis aimed to determine the technique with the highest pooled detection rate (DR) for the identification of SLN and compare the average number of SLNs detected by planar lymphoscintigraphy (PL), single-photon emission computed tomography/computed tomography (SPECT/CT), blue dye and indocyanine green (ICG) fluorescence.; Methods: The meta-analysis was conducted according to the PRISMA guideline. The search string was: "sentinel" and "vulv*", with date restriction from 1st January 2010 until Dec 31st, 2020. Three investigators selected studies based on: (1) a study cohort or a subset of a minimum of 10 patients with vulvar cancer undergoing either PL, SPECT/CT, blue-dye, or ICG fluorescence for the identification of SLN; (2) the possibility to extrapolate the DR or the average number of SLNs detected by a single technique (3) no evidence of other malignancies in the patient history.; Results: A total of 30 studies were selected. In a per-patient and a per-groin analysis, the DR for SLN of PL was respectively 96.13% and 92.57%; for the blue dye was 90.44% and 66.21%; for the ICG, the DR was 91.90% and 94.80%. The pooled DR of SPECT/CT was not calculated, since only two studies were performed in this setting. At a patient-based analysis, no significant difference was documented among PL, blue dye, and ICG (p = 0.28). At a per-groin analysis, PL and ICG demonstrated a significantly higher DR compared to blue dye (p < 0.05). The average number of SLNs, on a per-patient analysis, was available only for PL and ICG with a median number of 2.61 and 1.78 lymph nodes detected, respectively, and no significant statistical difference.; Conclusions: This meta-analysis favors the use of ICG and PL alone and in combination over blue dye for the identification of the SLN in vulvar cancer. Future studies may investigate whether the combined approach allows the highest DR of SLN in patients with vulvar cancer. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Di Giorgio, A., et al. (2019). "From palliation to cure: PIPAC for peritoneal malignancies." Minerva Medica 110(4): 385-398.
	INTRODUCTION: Systemic chemotherapy offers poor control over peritoneal disease, maybe as a consequence of restricted drug availability within the abdominal cavity. Locoregional chemotherapy may overcome these shortcomings but its administration is limited to a few patients with confined peritoneal spread. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) emerged in the last years as a novel method of intraperitoneal drug administration. EVIDENCE ACQUISITION: We report a meta-analysis of published studies on PIPAC safety and pathological anti-tumoral efficacy on PC from various tumor entities, with the aim of providing more evidence to support further research. This systematic review and meta-analysis were designed, conducted and reported according to the PRISMA statement. EVIDENCE SYNTHESIS: An overall pathological response rate of 43.7% was calculated on a total of 668 patients who underwent 1480 PIPAC cycles across the 20 studies. Pooled severe adverse events rate (CTCAE grade 3-4) was 10% and seven deaths across all studies were reported, of which only four were related to PIPAC. CONCLUSION(S): PIPAC is a safe procedure which has a relevant anti-tumoral activity on peritoneal carcinomatosis. Further studies, even in the early stage of disease, are awaited to assess the clinical benefit of PIPAC. This review may serve as a reliable basis for future research.Copyright © 2019 EDIZIONI MINERVA MEDICA.

Di, M., et al. (2023). "Ovarian stimulation protocols for poor ovarian responders: a network meta-analysis of randomized controlled trials." Archives of Gynecology and Obstetrics 307(6): 1713-1726.
	Objective: To evaluate the efficacy of manifold ovarian stimulation protocols for patients with poor ovarian response.; Methods: PubMed, Embase, Cochrane Library and Web of Science were systematically searched until February 14, 2021. Primary outcomes included clinical pregnancy rate per initiating cycle and low risk of cycle cancellation. Secondary outcomes included number of oocytes retrieved, number of metaphase II (MII) oocytes, number of embryos obtained, number of transferred embryos, endometrial thickness on triggering day and estradiol (E 2 ) level on triggering day. The network plot, league table, rank probabilities and forest plot of each outcome measure were drawn. Therapeutic effects were displayed as risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs).; Results: This network meta-analysis included 15 trials on 2173 participants with poor ovarian response. Delayed start GnRH antagonist was the best regimen in terms of clinical pregnancy rate per initiating cycle (74.04% probability of being the optimal), low risk of cycle cancellation (75.30%), number of oocytes retrieved (68.67%), number of metaphase II (MII) oocytes (97.98%) and endometrial thickness on triggering day (81.97%), while for E 2 level on triggering day, microdose GnRH agonist (99.25%) was the most preferred. Regarding number of embryos obtained and number of transferred embryos, no statistical significances were found between different ovarian stimulation protocols.; Conclusion: Delayed start GnRH antagonist and microdose GnRH agonist were the two superior regimens in the treatment of poor ovarian response, providing favorable clinical outcomes. Future investigation is needed to confirm and enrich our findings. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Di Tucci, C., et al. (2019). "Immunotherapy in endometrial cancer: new scenarios on the horizon." Journal of Gynecologic Oncology 30(3): e46.
	This extensive review summarizes clinical evidence on immunotherapy and targeted therapy currently available for endometrial cancer (EC) and reports the results of the clinical trials and ongoing studies. The research was carried out collecting preclinical and clinical findings using keywords such as immune environment, tumor infiltrating lymphocytes, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, immune checkpoint inhibitors, anti-PD-1/PD-L1 antibodies and others' on PubMed. Finally, we looked for the ongoing immunotherapy trials on ClinicalTrials.gov. EC is the fourth most common malignancy in women in developed countries. Despite medical and surgical treatments, survival has not improved in the last decade and death rates have increased for uterine cancer in women. Therefore, identification of clinically significant prognostic risk factors and formulation of new rational therapeutic regimens have great significance for enhancing the survival rate and improving the outcome in patients with advanced or metastatic disease. The identification of genetic alterations, including somatic mutations and microsatellite instability, and the definition of intracellular signaling pathways alterations that have a major role in in tumorigenesis is leading to the development of new therapeutic options for immunotherapy and targeted therapy.

Di Vito, M., et al. (2020). "Is aromatherapy effective in obstetrics? A systematic review and meta-analysis." Phytotherapy research : PTR.
	The aim of this systematic review is to collect clinical trials conducted using essential oils (EOs) in obstetric symptoms by evaluating if and in which context the aromatherapy practice is effective in obstetrics. The research was conducted by using the databases of EMBASE, Medline, Biosis and Toxcenter, PubMed, and Google Scholar search engine, selecting articles from January 2004 to July 2020. This study was performed according to the MOOSE and PRISMA guidelines. Only the randomized clinical trials were considered, and in cases of multiple publications, it was considered the most up to date information. Biases were highlighted. In the presence of homogeneous data, pooling statistics and meta-analysis were applied. The research led to 71 articles, 17 of which were eligible. Among the trials selected, eight investigated the effectiveness of EOs on anxiety, depression, and stress. Two concerned the treatment of nausea and vomiting, six evaluated the application of EOs on labor for pain treatment, and two showed the effectiveness in the treatment of episiotomy. The heterogeneity of works carried out so far has made it possible to develop a meta-analysis only in the field of pain treatment during childbirth, identifying the effectiveness of the EOs Lavandula spp. and Rosa damascena.

Di, W. and H. Jianrong (2023). "Quality of life in ovarian cancer patients treated with bevacizumab: a meta-analysis."
	
Di Yuan, M., et al. (2019). "Clinical evidence of Chinese medicine therapies for depression in women during perimenopause and menopause." Complementary Therapies in Medicine 47: 102071.
	Background: Depression is common in women during perimenopause and menopause. Complementary therapies such as acupuncture and Chinese herbal medicine (CHM) are often utilized by these women. However, the efficacy and safety of these treatments have not been systematically evaluated.; Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Nine English and Chinese databases were searched and search terms included perimenopause, menopause, depression, Chinese herbal medicine, acupuncture, RCTs, and their synonyms. Methodological quality was assessed using the Cochrane Risk of Bias Tool.; Results: A total of 18 RCTs were identified (6 CHM, 11 acupuncture related therapies, 1 combination of CHM and acupuncture). For Hamilton Rating Scale of Depression (HRSD) and Kuppermans Index of Menopause, tuina-massage, combined therapy of CHM plus acupuncture showed significant benefits at end of treatment compared to antidepressants. Either CHM and acupuncture reduced HRSD scores, indicating less severe depression, showing comparable effects to antidepressants.; Conclusion: CHM and acupuncture treatment in perimenopause and menopausal women resulted in reduced severity of depression. Results should be interpreted with caution given the small number of studies included in this review and further RCTs are warranted to validate findings from this review. (Copyright © 2019. Published by Elsevier Ltd.)

Diakosavvas, M., et al. (2022). "Myomectomy during pregnancy; diagnostical dilemmas: two case reports and a systematic review of the literature." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(5): 757-765.
	Myomectomy in pregnancy, until this day, remains very controversial. We present two cases of successful antepartum myomectomies performed in the second trimester of gestation. In both cases, the initial suspected origin of these tumours was the ovaries. However, as it was shortly after confirmed, since both women underwent laparotomy, the diagnosis of these masses was uterine fibroids. Both cases resulted on the live birth of two healthy infants via caesarean section. Secondarily, we conducted a thorough review of current data of myomectomies performed during pregnancy, including the characteristics and diagnosis of the myomas of pregnant women, the surgical details and complications, along with the outcomes of these gestations. Overall, the analysis of cases published in international literature, suggests that the surgical removal of myomas during pregnancy can be considered safe, given certain indications and considerations. Our review comprises of 71 women undergoing excision of fibroids during pregnancy. Only three cases ended in a miscarriage while the remaining 68 resulted in a second or third trimester delivery. However, the data concerning the safety of the procedure are scarce and originate mostly from case reports. Thus, conclusions on the exact maternal and obstetrical complication rates cannot be drawn.

Diakosavvas, M., et al. (2020). "Controversies in preoperative bowel preparation in gynecologic and gynecologic oncology surgery: a review of the literature." Archives of Gynecology and Obstetrics 302(5): 1049-1061.
	Purpose: The purpose of this review is to assess the impact of mechanical and oral antibiotics bowel preparation on surgical performance and to investigate their role before gynecologic surgical procedures regarding the infection rates. We also aim to study the updated evidence regarding the use of these different types of bowel preparation, as well as the current preoperative practice applied.; Methods: An extensive search of the literature was conducted with Medline/PubMed, and the Cochrane Library Database of Systematic Reviews being used for our primary search.; Results: To date, due to the conflicting guidelines by the scientific societies, surgeons do not use a specific pattern of bowel preparation regimen. There are no strong evidence supporting mechanical bowel preparation, but instead, in many cases, patients' adverse effects, both physiological and psychological have been noted. On the other hand, the combined use of oral antibiotic and mechanical bowel preparation has been proven beneficial in colorectal surgery in reducing postoperative morbidities.; Conclusion: Based on current literature, in gynecologic surgeries with minimal probability of intraluminal entry, a regimen without any bowel preparation should be applied. The combined administration of both mechanical and oral antibiotic bowel preparation, or even the use of the oral antibiotics alone, should be preserved for cases of increased complexity, where bowel involvement is highly anticipated, such as in gynecologic oncology, as stated in the ERAS protocols. Nonetheless, further research specific to gynecologic surgery is required.

Diamond, M. P., et al. (2019). "A 12-month extension study to evaluate the safety and efficacy of asoprisnil in women with heavy menstrual bleeding and uterine fibroids." Human Reproduction Open 2019(4): hoz027.
	Study Question: What is the safety and efficacy profile during long-term (12-24 months) uninterrupted treatment with the selective progesterone receptor modulator asoprisnil, 10 and 25 mg in women with heavy menstrual bleeding (HMB) associated with uterine fibroids?; Summary Answer: Uninterrupted treatment with asoprisnil should be avoided due to endometrial safety concerns and unknown potential long-term consequences.; What Is Known Already: Asoprisnil was well tolerated in shorter-term studies and effectively suppressed HMB and reduced fibroid volume.; Study Design Size Duration: Women with uterine fibroids who had previously received placebo ( n = 87) or asoprisnil 10 mg ( n = 221) or 25 mg ( n = 215) for 12 months in two double-blind studies entered this randomized uncontrolled extension study and received up to 12 additional months of treatment followed by 6 months of post-treatment follow-up. Women who previously received placebo were re-randomized to either asoprisnil 10 or 25 mg for the extension study. This report focuses on the 436 women who received asoprisnil in the double-blind studies and this extension study. Results for women who previously received placebo in the double-blind studies are not described.; Participants/materials Setting Methods: Women ≥18 years of age who completed a 12-month, double-blind, placebo-controlled study, had estradiol levels indicating that they were not menopausal and had no endometrial hyperplasia or other significant endometrial pathology were eligible. The safety endpoints were focused on endometrial assessments. The composite primary efficacy endpoint was the proportion of women who demonstrated a response to treatment by meeting all three of the following criteria at the final month for participants who prematurely discontinued or at month 12 for those who completed the study: a reduction from initial baseline to final visit of ≥50% in the menstrual pictogram score, hemoglobin concentration ≥11 g/dl or an increase of ≥1 g/dl from initial baseline at the final visit, and no surgical or invasive intervention for uterine fibroids. Other efficacy endpoints included rates for amenorrhea and suppression of bleeding, changes in fibroid and uterine volume and changes in hematologic parameters. No statistical tests were planned or performed for this uncontrolled study.; Main Results and Role of Chance: Imaging studies revealed a progressive increase in endometrial thickness and cystic changes that frequently prompted invasive diagnostic procedures. Endometrial biopsy results were consistent with antiproliferative effects of asoprisnil. Two cases of endometrial cancer were diagnosed. At the final month of this extension study (total duration of uninterrupted treatment up to 24 months), the primary efficacy endpoint was achieved in 86 and 92% of women in the asoprisnil 10- and 25-mg groups, respectively. During each month of treatment, amenorrhea was observed in the majority of women (up to 77 and 94% at 10 and 25 mg, respectively). There was a progressive, dose-dependent decrease in the volume of the primary fibroid with asoprisnil 10 and 25 mg (-55.7 and -75.2% median decrease, respectively, from baseline [i.e. the beginning of the placebo-controlled study] to month 12 [cumulative months 12-24] of this extension study). These effects were associated with improvements in quality of life measures.; Limitations Reasons for Caution: This study was uncontrolled, which limits the interpretation of safety and efficacy findings. The study also had multiple protocol amendments with the addition of diagnostic procedures and, because no active comparator was included, the potential place of asoprisnil in comparison to therapies such as GnRH agonists and surgery cannot be determined.; Wider Implications of the Findings: Long-term, uninterrupted treatment with asoprisnil leads to prominent cystic endometrial changes that are consistent with the 'late progesterone receptor modulator' effects, which prompted invasive diagnostic procedures, although treatm nt effic cy is maintained. Although endometrial cancers were uncommon during both treatment and follow-up, these findings raise concerns regarding endometrial safety during uninterrupted long-term treatment with asoprisnil. This study shows that uninterrupted treatment with asoprisnil should be avoided due to safety concerns and unknown potential long-term consequences.; Study Funding/competing Interests: AbbVie Inc. (prior sponsor, TAP Pharmaceutical Products Inc.) sponsored the study and contributed to the design and conduct of the study, data management, data analysis, interpretation of the data and the preparation and approval of the manuscript. Financial support for medical writing and editorial assistance was provided by AbbVie Inc. M. P. Diamond received research funding for the conduct of the study paid to the institution and is a consultant to AbbVie. He is a stockholder and board and director member of Advanced Reproductive Care. He has also received funding for study conduct paid to the institution for Bayer and ObsEva. E. A. Stewart participated as a site investigator in the phase 2 study of asoprisnil and served as a consultant to TAP Pharmaceuticals during the time of design and conduct of the studies while on the faculty of Harvard Medical School and Brigham and Women's Hospital, Boston, MA. In the last 3 years, she has received support from National Institutes of Health grants HD063312, HS023418 and HD074711. She has served as a consultant for AbbVie Inc., Allergan, Bayer HealthCare AG and Myovant for consulting related to uterine leiomyoma and to Welltwigs for consulting related to infertility. She has received royalties from UpToDate and the Med Learning Group. A.R.W. Williams has acted as a consultant for TAP Pharmaceutical Products Inc. and Repros Therapeutics Inc. He has current consultancies with PregLem SA, Gedeon Richter, HRA Pharma and Bayer. B.R. Carr has served as consultant and received research funding from AbbVie Inc. and Synteract (Medicines360). E.R. Myers has served as consultant for AbbVie Inc., Allergan and Bayer. R.A. Feldman received compensation for serving as a principal investigator and participating in the conduct of the trial. W. Elger was a co-inventor of several patents related to asoprisnil.C. Mattia-Goldberg is a former employee of AbbVie Inc. and owns AbbVie stock or stock options. B.M. Schwefel and K. Chwalisz are employees of AbbVie Inc. and own AbbVie stock or stock options.; Trial Registration Number: NCT00156195 at clinicaltrials.gov. (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Dias Amanda Tamiris, B., et al. (2021). "Effectiveness of the use of Low Molecular Heparin in patients with repetition abortion history: Systematic review and meta-analysis." JBRA Assisted Reproduction 25(1): 10-27.
	Objective: To evaluate the efficacy and safety of using low molecular weight heparin (LMWH) in women with a history of recurrent abortion without an identified cause.; Methods: To develop a systematic review to select the studies. Total found 437 papers. Seven studies were completed or requested. The following variables were analyzed: clinical pregnancy, implantation rate, live births, abortion, premature birth, pregnancy, continuous pregnancy, beyond the 20th gestational week, congenital abnormality, hemorrhage, preeclampsia, placental premature detachment.; Results: The LMWH group had a higher incidence of continuous pregnancy after the 20th week of gestation and there was no significant difference between the LMWH group and the expectant management group in the analysis of other variables.; Conclusions: There was no data showing risk and/or less use of LMWH compared to expectant management; on the contrary, LMWH use increased the incidence of evolutionary pregnancy after the 20th gestational week. LMWH has some influence on prophylactic treatment of repeat abortion for unknown cause.

Dias Sávia Francisca, L., et al. (2019). "Scientific and technological prospection on transdermal formulations and complementary therapies for the treatment of primary dysmenorrhea." Expert opinion on therapeutic patents 29(2): 115-126.
	Introduction: Primary dysmenorrhea (PD) is another term for idiopathic menstrual cramps. Treatments include the use of oral non-steroidal anti-inflammatory drugs (NSAIDs). These drugs have several side effects. The objective of this study was to perform a systematic review on the transdermal administration of drugs and the use of alternative therapies for the treatment of PD.; Areas Covered: The article bases were Web of Science, PubMed and Sciencedirect and the patent bases were INPI, EPO and WIPO with publications on Primary Dysmenorrhea and associations with Transdermal Administration; Complementary Therapies and Medicinal Plants. 21 articles and 12 patents were analyzed. The results demonstrate the need for alternative therapies for the treatment of PD, with greater effectiveness and lower side effects, mainly in an attempt to reduce the intensity and duration of pain as well as reducing the continuous use of medications.; Expert Opinion: The study of technological prospection highlighted the relevant importance in seeking new methods for the relief of the symptoms provoked by this condition. The perspectives coexist in the discovery of new natural and biotechnological pharmacological applications, mainly in the development of new devices capable of facilitating and optimizing this form of administration in an attempt to reduce side effects.

Díaz-Álvarez, L., et al. (2022). "Does the Contractile Capability of Pelvic Floor Muscles Improve with Knowledge Acquisition and Verbal Instructions in Healthy Women? A Systematic Review." International Journal of Environmental Research and Public Health 19(15).
	Seventy percent of women with pelvic floor dysfunctions (PFDs) are estimated to present deficient consciousness of their pelvic floor muscles (PFMs) and poor ability to contract them. Improving the proprioception of PFMs, defined as the capacity to know the status and position of each body part, and adequately contracting them could be a protective factor to prevent the appearance of PFDs in the general female population. This study aimed to identify the effectiveness of educational interventions and verbal instructions on how to contract and exercise the PFMs to improve the proprioception of the PFMs in women. A systematic search of studies published in the last 20 years until March 2022 was conducted in the PubMed, Cochrane Library, Web of Science, Scopus, PEDro, Lilacs, and Dialnet databases. A meta-analysis could not be performed due to the heterogeneity in the types of studies and included populations. This review followed the PRISMA guidelines for the design, search, and reporting of studies. The methodological quality was analysed via the PEDro and the Newcastle-Ottawa scales in the case of randomised clinical trials and non-randomised studies, respectively, while the quality of evidence was determined using the SIGN grading system for evidence-based guidelines. Descriptive and experimental studies published in English, Spanish, or Portuguese that evaluated the contractile capability of the PFMs in healthy women or women without a previous diagnosis of PFD were included. Seven articles that included a total of 2507 women were found, three of which were clinical trials with PEDro scores between 5 and 9 points out of 10 and four of which were non-randomised studies with NOS scores between 6 and 8 points out of 10. The outcomes were measured through vaginal palpation, visual observation, questionnaires for PFD symptoms, and self-perception reports. This review discriminated between two types of intervention, educational programmes and verbal instructions, and evaluated the changes observed in PFM strength and knowledgeability and the symptoms of PFDs. The findings showed that educational interventions and verbal instructions improve the proprioception of PFMs in women of all ages that are healthy or without a previous diagnosis of PFDs as well as their knowledge about the pelvic floor, healthy lifestyle habits, and symptoms that are potentially indicative of PFDs. Further high-quality randomised clinical trials are warranted to draw definitive conclusions about the effectiveness of educational interventions to improve the proprioception of the PFMs in women considered healthy or with mild symptoms that may be indicative of PFDs.

Díaz-Feijoo, B., et al. (2022). "A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society: 1463-1468.
	Background: Multimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian cancer is unclear.; Primary Objective: To compare the post-operative complications of a multimodal prehabilitation program in patients undergoing cytoreductive surgery for advanced ovarian cancer with standard pre-operative care.; Study Hypothesis: Multimodal prehabilitation reduces post-operative complications in patients undergoing cytoreductive surgery for advanced ovarian cancer and subsequently reduces the length of hospital stay and time to initiation of adjuvant therapy.; Trial Design: This prospective, multi-institutional, randomized clinical trial will randomize candidates for surgery to either the standard of care or multimodal prehabilitation consisting of (1) 2- or 3-weekly supervised high-intensity resistance training sessions and promotion of physical activity through a mobile phone application; (2) respiratory physiotherapy; (3) nutrition counseling with supplementation as needed; and (4) weekly psychological and cognitive behavioral sessions. Baseline, pre-operative and 1 month post-operative data will be collected. An independent blinded evaluator will collect intra- and post-operative surgical data.; Major Inclusion/exclusion Criteria: Women with advanced ovarian cancer International Federation of Gynecology and Obstetrics (2014) stage III or IV scheduled to undergo primary debulking surgery, interval debulking surgery,or secondary or tertiary cytoreductive surgery will be included. Women are eligible if they are able to undergo a minimum of 2 weeks of prehabilitation prior to surgery. Patients with <75% adherence to the total program will be excluded.; Primary Endpoint: Post-operative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery according to the Comprehensive Complication Index.; Sample Size: 146 patients will be included, 73 in each group.; Estimated Dates for Completing Accrual and Presenting Results: Accrual should be completed in December 2024 with results reported soon thereafter.; Trial Registration Number: NCT04862325.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Díaz-Feijoo, B., et al. (2021). "Surgical complications comparing extraperitoneal vs transperitoneal laparoscopic aortic staging in early stage ovarian and endometrial cancer." Gynecologic Oncology 160(1): 83-90.
	OBJECTIVE: To determine whether the extraperitoneal approach for paraaortic staging lymphadenectomy results in a lower rate of surgical complications compared to the transperitoneal approach, without compromising oncological outcomes. METHODS: Prospective randomized multicenter study of patients with early endometrial or ovarian cancer undergoing paraaortic lymphadenectomy in 2010-2019. Patients were randomized to minimally invasive surgery (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥500 mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindo ≥ IIIA), impossibility to complete the procedure, or conversion to laparotomy. RESULTS: There were 103 patients in the extraperitoneal group and 100 in the transperitoneal group. Differences in the composite outcome (transperitoneal 26.0% vs, extraperitoneal 18.4%; P = 0.195) were not found. Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7-17] vs, 14 [10-19]: P = 0.026). Older age and greater body mass index (BMI) or waist-to-hip ratio (WHR) increased the risk for surgical complications independently of the laparoscopic approach. CONCLUSIONS: The extraperitoneal approach did not show differences regarding surgical and oncological parameters compared with the transperitoneal approach, although the number of aortic nodes retrieved was higher. The decision to use one or another laparoscopic route is a matter of the surgeon preference. Trial registration ClinicalTrials.gov.identifier: NCT02676726.

DiCarlo-Meacham, A. M., et al. (2023). "Reduced versus standard intradetrusor OnabotulinumtoxinA injections for treatment of overactive bladder." Neurourology and Urodynamics 42(1): 366-374.
	Background: Intradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder. Method(s): In this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization. Result(s): Data from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms. Conclusion(s): A reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.Copyright © 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

Dickey, B. L., et al. (2021). "An updated systematic review of HPV genotype distribution by cervical disease grade in women living with HIV highlights limited findings from Latin America." Sexually Transmitted Diseases.
	Cervical cancer is five times more likely among women living with HIV (WHIV), likely due to higher prevalence of HPV. Despite evidence of higher rates with multiple HPV genotypes in WHIV, there are no recommendations for triage by HPV genotyping specific to WHIV. In Latin America/Caribbean (LAC) rates are high and vary significantly. To guide optimization of HPV-based cervical cancer screening among WHIV in LAC, review of current literature was completed to assess HPV genotype distribution by cervical disease grade in WHIV in this region; and further expanded globally for comparison across regions.A systematic review of the literature from June 2016 to January 2020 revealed 15 studies reporting HPV genotype distribution by cervical disease state (normal, low-grade disease, high-grade disease, and invasive cervical cancer) across different global regions.Across all studies, there were 6,928 WHIV from 4 global regions, 3,952 of whom were HPV-positive. Three studies from LAC were reviewed, with one providing enough detail to describe HPV genotypes by cervical disease grade and identified type 31 and 35 in high-grade cervical lesions. Of the studies included, 4 from Africa and Europe/North America each, and 1 from Asia included data that were able to be summarized.Latin America, a region which experiences high rates of HPV, HIV, and cervical disease, had few published studies reporting HPV genotypes by cervical disease grade, with one reporting individual HPV genotype and specific cervical disease grade. Identifying HPV types associated with CIN2+ in WHIV in this region has the potential to improve screening and treatment for cervical cancer prevention and should be the focus of future research.

Diebold, A., et al. (2021). "Testing the effects of a prenatal depression preventive intervention on parenting and young children's self-regulation and functioning (EPIC): protocol for a longitudinal observational study." BMC public health 21(1): 1368.
	Background: Perinatal depression is a pervasive public health concern that disproportionately affects low-income women and can have negative impacts on parenting and child developmental outcomes. Few interventions focus on preventing perinatal depression. Previous studies suggest that Mothers and Babies is efficacious in preventing the worsening of depressive symptoms and the onset of postpartum depression. This manuscript presents the protocol of the EPIC study (Effects of a Prenatal Depression Preventive Intervention on parenting and young children's Self-Regulation and Functioning) to test the effects of Mothers and Babies on parenting and child developmental outcomes through 54 months postpartum. EPIC is an observational study that builds on a completed cluster-randomized trial (CRT). Innovations of this study are direct observations of a subsample of mother-child dyads and the inclusion of fathers/caregivers' variables as moderators of maternal mental health.; Methods: For this study, we plan to enroll 738 women with children under 30 months old, ≥18 years old, and who speak English or Spanish. Additionally, 429 fathers, partners, or other adult caregivers will be recruited through women participating in the study. Women will be recruited through the parent study (intervention and control participants) or through one of 10 home visiting programs in Illinois (control participants). Data collection will take place through maternal self-report at five time points (when the child is 30, 36, 42, 48, and 54 months), paternal self-report at three time points (when the child is 30, 42, and 54 months), and through mother-child observations at three time points (when the child is 36, 42, and 48 months). Outcome domains include maternal mental health, cognitive-behavioral and parenting skills, and child self-regulation and functioning. Moderators include the contributions of fathers/caregivers, race-ethnicity, and socioeconomic disadvantage. Power and sample size were calculated assuming a two-sided 5% type I error rate and assumed analyses on the individual level.; Discussion: This study has several key strengths and innovations, as well as great potential significance to influence the long-term trajectories of parenting and child development via prenatal intervention.; Trial Registration: The study was retrospectively registered at ClinicalTrials.gov (Identifier: NCT04296734 ) on March 5, 2020. (© 2021. The Author(s).)

Diem, S. J., et al. (2020). "Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: A pooled analysis of individual participant data from four MsFLASH trials." Menopause 27(10): 1126-1136.
	Objective:The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects on menopause-related QOL relative to control in women with VMS. Method(s):We pooled individual-level data from 1,005 peri-and postmenopausal women with 14 or more VMS/week across the four RCTs. Interventions included escitalopram 10 to 20mg/d; yoga/aerobic exercise; 1.8g/d omega-3-fatty acids; oral 17-beta-estradiol 0.5mg/d; venlafaxine XR 75mg/d; and cognitive behavioral therapy for insomnia (CBT-I). Outcomes measures were the Menopause-specific Quality of Life scale and its subscales. Result(s):Significant improvements in total Menopause-specific Quality of Life from baseline were observed with estradiol, escitalopram, CBT-I, and yoga, with mean decreases of 0.3 to 0.5 points relative to control. The largest improvement in the vasomotor subscale was observed with estradiol (-1.2 points), with more modest but significant effects seen with escitalopram, yoga, and CBT-I. Significant improvements in the psychosocial subscale were observed for escitalopram, venlafaxine, and CBT-I. For the physical subscale, the greatest improvement was observed for CBT-I and exercise, whereas for the sexual subscale, the greatest improvement was observed for CBT-I, with yoga and estradiol demonstrating smaller effects. Conclusion(s):These results suggest that for menopause-related QOL, women have a variety of treatment strategies to choose from and can select an approach based on most bothersome symptoms and individual preferences.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Dieter Alexis, A., et al. (2019). "Catheter burden following urogynecologic surgery." American Journal of Obstetrics and Gynecology 221(5): 507.e501-507.e507.
	Background: Data on the experience that women who undergo urogynecologic surgery have with postoperative catheterization are severely limited. As the importance of our patients' perioperative experience becomes more valued, assessment of the burden of postoperative catheterization, which has not yet been performed, is increasingly needed.; Objective: The aim of this study was to compare catheter burden in women who self-selected use of an indwelling Foley catheter vs clean intermittent self-catheterization for voiding dysfunction after reconstructive pelvic surgery.; Study Design: This is a nested study within a nonblinded randomized controlled trial of 2 different voiding trial protocols that was conducted from March to October 2017. Women who underwent pelvic organ prolapse and/or stress urinary incontinence surgery who were English speaking and ≥18 years old with a preoperative postvoid residual <100 mL were included. Participants who did not pass their voiding trial were discharged with an indwelling Foley catheter or self-catheterization per participant preference. Our primary outcome was catheter burden at 1 week after surgery assessed by the Short-Term Catheter Burden Questionnaire, which is a validated 6-item survey comprised of 2 subscales: difficulty of use and embarrassment. Scores range from 3-15 with higher scores indicating greater difficulty and/or embarrassment, and the sum of the 2 subscale scores measures total catheter burden with a higher score indicating greater burden. Secondary outcomes included the rate of urinary tract infection, the number of postoperative clinic visits, and the number of postoperative phone calls.; Results: Of 150 participants, 77 women (51%) did not pass their voiding trial; of those, 47 women (61%) were discharged home with an indwelling catheter and 30 women (39%) with self-catheterization. Baseline demographics were similar, except that women who chose an indwelling Foley catheter were older (62±11 vs 55±11 years; P<.01). There were no significant differences between indwelling Foley catheter and self-catheterization in total catheter burden score (18±5 vs 18±6; P=.77), difficulty of use subscale score (8±3 vs 9±3; P=.20), or embarrassment subscale score (10±4 vs 9±4; P=.12). For secondary outcomes, there were no significant differences in rate of urinary tract infection (23% indwelling vs 30% self-catheterization; P=.60). Consistent with study protocol, women who were discharged with an indwelling Foley catheter did have more postoperative clinic visits (2±1 vs 1±1 visits; P<.01), and those women who were discharged with self-catheterization had more postoperative phone calls (2±3 vs 5±3 phone calls; P<.01). Otherwise there was no significant difference in nonvoiding-related clinic visits (1±1 visits for indwelling and self-catheterization; P=.15) or postoperative phone calls (1±2 indwelling vs 2±3 self-catheterization calls; P=.31).; Conclusion: In women who used either an indwelling Foley catheter or clean intermittent self-catheterization for management of postoperative voiding dysfunction after pelvic reconstructive surgery, there were no differences in difficulty of use, embarrassment, or overall catheter burden. There were also no differences in nonvoiding-related postoperative phone calls or clinic visits, with similar rates of urinary tract infection between the 2 groups. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Dietl, A., et al. (2020). "Tumor Handling of Early-stage Cervical Cancer: A Literature Analysis of Villoglandular Adenocarcinoma of the Cervix." Anticancer Research 40(6): 3049-3053.
	Background/aim: Recent studies have demonstrated the inferior overall survival outcomes of patients with early-stage cervical cancer who undergo minimally invasive surgery (MIS). One possible explanation for these unexpected results is intraoperative tumor manipulation.; Materials and Methods: Considering this hypothesis, we have reviewed the literature on the oncological outcomes of patients with villoglandular adenocarcinoma (VGA) of the cervix, an uncommon variant of cervical cancer that has an excellent prognosis.; Results: VGA generally presents as an exophytic mass arising from the endocervix. In a systematic review, we identified 221 patients treated surgically for VGA (FIGO stage Ia-Ib 1 ). Of these, 11 developed recurrence, and four died. The recurrence sites in 8 cases were the pelvis (n=3), vaginal cuff (n=3), episiotomy scar (n=1), and cervix (n=1). Furthermore, 23 VGA-patients were treated by MIS, four experienced recurrence, and one died. Three intraabdominal metastases after MIS were reported.; Conclusion: Excessive tumor-handling during MIS or manipulations, e.g. cervix-dilation (during delivery), can worsen the otherwise excellent prognosis. (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Dietl Anna, K., et al. (2021). "Villoglandular adenocarcinoma of the uterine cervix: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 304(2): 317-327.
	Purpose: Villoglandular adenocarcinoma (VGA) of the uterine cervix has been classified as a rare subtype of cervical adenocarcinoma with good prognosis. A conservative surgical approach is considered feasible. The main risk factor is the presence of other histologic types of cancer. In this largest systematic review to date, we assess oncological outcomes associated with conservative therapy compared to those associated with invasive management in the treatment of stage Ia and Ib 1 VGA.; Methods: Case series and case reports identified by searching the PubMed database were eligible for inclusion in this review (stage Ia-Ib 1 ).; Results: A total of 271 patients were included in our literature review. 54 (20%) patients were treated by "conservative management" (conization, simple hysterectomy, and trachelectomy) and 217 (80%) by "invasive management" (radical hysterectomy ± radiation, hysterectomy, and radiation). Recurrences of disease (RODs) were found in the conservative group in two (4%) cases and in the invasive group in nine (4%) cases. There was no significant difference in disease-free survival (DFS) according to conservative or invasive treatment (p = 0.75). The histology of VGA may be complex with underlying usual adenocarcinoma (UAC) combined with VGA.; Conclusion: The excellent prognosis of pure VGA and the young age of the patients may justify the management of this tumor using a less radical procedure. The histological diagnosis of VGA is a challenge, and pretreatment should not be based solely on a simple punch biopsy but rather a conization with wide tumor-free margins. (© 2021. The Author(s).)

Dietz de Loos, A., et al. (2022). "Pregnancy Rate and Outcomes Following a Randomized Controlled Three-component Lifestyle Intervention in Women with PCOS." Human reproduction (Oxford, England) 37: i482‐i483.
	Study question: What is the impact of a three‐component lifestyle intervention on the pregnancy rate, time to pregnancy and pregnancy complications in women with polycystic ovary syndrome? Summary answer: A non‐significant positive trend in pregnancy outcomes was demonstrated in favor of the lifestyle intervention groups, in line with the weight loss achieved per group. What is known already: PCOS (polycystic ovary syndrome) is associated with overweight and obesity. Women with PCOS and overweight or obesity present with more pronounced reproductive derangements. Moreover, when pregnant, pregnancy complications such as gestational diabetes, hypertensive disorders and preterm birth seem to be more prevalent in this population. The first line treatment for women with PCOS and overweight or obesity is a multi‐component lifestyle intervention. Data on pregnancy outcomes after multi‐component lifestyle interventions in women with PCOS are scarce. Study design, size, duration: The present study is a one‐year randomized controlled trial to investigate the effect of a three‐component (cognitive behavioral therapy, healthy diet and physical therapy) lifestyle intervention (LSI) with or without Short Message Service (SMS) on pregnancy leading to live birth, pregnancy complications and outcomes within 24 months after the start of the lifestyle intervention compared to care as usual (CAU). Participants/materials, setting, methods: Women diagnosed with PCOS according to the Rotterdam 2003 criteria and a BMI above 25 kg/m2 were included. A total of 183 participants were randomly assigned to three groups: 1) three‐component lifestyle intervention with SMS (SMS+); 2) three‐component lifestyle intervention without SMS (SMS‐); 3) care as usual (CAU): encourage to lose weight autonomously (control group). Pregnancy and neonatal outcomes were collected from the Dutch Bureau of Statistics (CBS) combined with the Dutch Perinatal registry (Perined). Main results and the role of chance: Within 24 months after the start of the intervention the pregnancy rate leading to live birth was 41.7% (25/60) within SMS+, 38.1% (24/63) within SMS‐ and 38.3% (23/60) within CAU. This was non‐significant between the groups. Mean time to pregnancy for SMS+ was 18.3 months, 19.1 months for SMS‐ and 19.4 months for CAU (p=0.775). Gestational diabetes (LSI: 8.2% vs CAU: 21.7%, p=0.133), hypertensive disorders (LSI: 8.2% vs CAU: 13.0%, p=0.673) and preterm birth (LSI: 12.2% vs CAU: 17.4%, p=0.716) rates were all lower in the LSI groups (SMS+ and SMS‐ combined) compared to CAU. Limitations, reasons for caution: Although significantly less than the LSI groups, even the CAU group achieved weight loss, which may give an underestimation of the effect of the lifestyle intervention with regard to pregnancy outcomes. Wider implications of the findings: Weight loss overall seems to have a positive effect on pregnancy outcomes, and multi‐component lifestyle interventions are needed to achieve weight loss.

Dietz de Loos, A., et al. (2023). "Pregnancy Outcomes in Women with PCOS: Follow-Up Study of a Randomized Controlled Three-Component Lifestyle Intervention." Journal of Clinical Medicine 12(2).
	Women with polycystic ovary syndrome (PCOS) and excess weight often present with reproductive derangements. The first-line treatment for this population is a multi-component lifestyle intervention. This follow-up study of a randomized controlled trial based on data from the Dutch Perinatal registry was conducted to study the effect of a one-year three-component (cognitive behavioral therapy, healthy diet, and exercise) lifestyle intervention on pregnancy outcomes in women with PCOS and overweight or obesity. Women diagnosed with PCOS, a BMI ≥ 25 kg/m², and a wish to conceive were randomized to either three-component lifestyle intervention (LSI, n = 123), and care as usual (CAU, n = 60) where they were encouraged to lose weight autonomously. Conception resulting in live birth was 39.8% (49/123) within LSI and 38.3% (23/60) within CAU ( p = 0.845). In total, 58.3% conceived spontaneously. Gestational diabetes (LSI: 8.2% vs. CAU: 21.7%, p = 0.133), hypertensive disorders (LSI: 8.2% vs. CAU 13.0%, p = 0.673), and preterm birth (LSI: 12.2% vs. CAU: 17.4%, p = 0.716) rates were all lower in LSI compared to CAU. This follow-up study showed no significant differences in conception resulting in live birth rates between LSI and CAU. Nonetheless, a large proportion eventually conceived spontaneously. Moreover, after LSI, the number of uneventful pregnancies was lower compared to care as usual.

Digklia, A., et al. (2022). "Trabectedin and Durvalumab Combination Is Feasible and Active in Relapsing Ovarian Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 28(9): 1745-1747.
	The combination of chemotherapy and immune therapies still promises to synergize for prolonged tumor control. However, the quest for optimal combinations tailored for tumor histology remains ongoing. A recent study provides evidence on the feasibility of the trabectedin/durvalumab combination and reports on interesting preliminary efficacy. See related article by Toulmonde et al., p. 1765. (©2022 American Association for Cancer Research.)

Dikke, G. B., et al. (2023). "VAGINAL DILATERS IN THE PREVENTION AND TREATMENT OF STENOSIS AND VAGINAL PAIN SYNDROMES." Akusherstvo i Ginekologiya (Russian Federation) 2023(12): 181-188.
	This article presents up-to-date information on the use of vaginal dilators in gynecology, taking into account the indications for their use and effectiveness. The findings of 36 articles found in the databases Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, eLibrary were analyzed over the period 2014-2023 using keywords. The results of the analysis showed that there are the following indications for the use of vaginal dilators: condition after radiation therapy for cancer of the vulva, cervix, uterus, anogenital area (high risk of vaginal stenosis); scars/stenosis after episiotomy or perineal rupture during childbirth, vaginoplasty surgery (neovagina, vaginal hypoplasia/agenesis, or Mayer-Rokitansky-Kuster-Hauser syndrome); dyspareunia, vaginismus, vulvodynia, sclerosing complications of skin diseases of the external genitalia (sclerotic lichen, lichen planus). The use of vaginal dilators is effective in 75-81% of patients for the prevention of vaginal stenosis after radiation therapy for cancer of the genitalia and anogenital area; it is effective in the treatment of hypoplasia/agenesis of the vagina in 75%, and is also effective in stenosis caused by sclerotic lichen and lichen planus. The success of therapy depends on informing and educating patients. Conclusion(s): The analysis of studies published over the past 10 years has shown the possibility of using vaginal dilators for various diseases, in particular for the prevention of vaginal stenosis after radiation therapy in patients treated for gynecological cancer, postpartum injuries, after gynecological operations on the vulva and vagina, as well as for stenosis caused by sclerotic lichen and lichen planus. Informing and educating patients influence the success of therapy. The use of vaginal dilators should become more widespread in clinical practice.Copyright © A group of authors, 2023.

Dikke, G. B., et al. (2021). "Immune-mediated mechanisms of the inflammatory response in women with combined infections of the lower genital tract." Obstetrics, Gynecology and Reproduction 15(3): 245‐257.
	Aim: to increase the effectiveness of combination therapy and reduce frequency of recurrences of inflammatory diseases in the lower genital tract of combined etiology. Materials and Мethods. There was conducted a prospective, randomized, blind, comparative clinical study. 80 women with vaginal microbiota disorders were examined randomized into 2 groups: group I (n = 40) ‐ antibiotic therapy was carried out in combination with the preparation Superlimph, group II (n = 40) ‐ a standalone antibacterial therapy; group III consisted of 20 patients lacking gynecological diseases considered to provide with control laboratory parameters. Clinical and laboratory methods were used: microscopy of vaginal smears, detection of viruses and sexually transmitted infections, measurement of serum cytokine levels ‐ interleukins (IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10), tumor necrosis factor alpha, (TNF‐α), interferon gamma (IFN‐γ). Results. It was found that clinical recovery occurred in 90.0 and 70.0 % of patients in group I and group II (р = 0.02), respectively. Microbiological recovery was observed in 100.0 and 67.5 % of patients, respectively (р = 0.003). In group I, the isolation of herpes simplex virus type 2 was found in 80.0 and 45.2 % of patients before and after treatment (p < 0.001), respectively, whereas in group II ‐ in 82.5 and 77.5 %, respectively (p = 0.58), between groups ‐ p < 0.001. Before treatment the level of all cytokines, excepting IFN‐γ, was higher than the reference values in both groups: in group I, their magnitude decreased after treatment (p < 0.001) and corresponded to the reference values; in group II no changes occurred. Three months after treatment, no relapses were observed in group I, whereas frequency of relapses in group II was 22.5 %, within 1 year ‐ 0 and 35.1 %, respectively. Predictors of recurrent dysbiosis (IL‐2, IL‐6 and TNF‐α in increased concentrations after a course of treatment) were identified. Conclusion. Treatment with a combined broad‐spectrum antimicrobial drug along with topical immunomodulatory agent containing exogenous cytokines is an effective strategy for treating concomitant dysbiosis and preventing relapse.

Dikke, G. B., et al. (2021). "Cytokine profile in patients with chronic endometritis and reproductive disorders." Voprosy Ginekologii, Akusherstva i Perinatologii 20(6): 82‐91.
	Objective. To study the immune response in patients with chronic endometritis (CE) of viral and bacterial etiology based on the evaluation of cytokine status as well as the efficiency of local therapy using a complex of natural exogenous cytokines. Patients and methods. A prospective randomized clinical trial, which included 76 women with CE and infertility, who received etiotropic antibacterial therapy prior to inclusion in the study, is presented. In group I (n = 36), patients were treated with a daily intravaginal administration of Superlymph 25 U for 20 days; in group II (n = 40), patients were under observation. We used a vaginal wet mount test, real‐time polymerase chain reaction (RT‐PCR) (to estimate virus shedding), and an analysis of serum cytokine levels (interleukins IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, and tumor necrosis factor alpha (TNF‐α)). Results. The herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) (80.6% and 80.0%, respectively) was predominantly detected in both groups of patients in combination with other types of herpesviruses (50.0% and 42.5%, respectively) and/or human papillomavirus (HPV) (50%). After treatment with Superlymph, virus shedding ceased in 66.7% of patients (p < 0.001). Before treatment, the levels of all cytokines were higher than the reference values (p < 0.001) in both groups (IL‐1β – 1.8 times, IL‐6 – 1.6 times, IL‐2 and IL‐8 – 1.2 times, TNF‐α – 1.4 times). After treatment, their values decreased in group I (p < 0.001 for each indicator). In group II, the changes were insignificant. Pregnancy occurred within 12 months in 30 (83.3%) patients in group I and in 24 (60.0%) patients in group II, and this result was statistically significantly higher in group I (p = 0.047). Conclusion. The role of viral and bacterial infections accompanied by an imbalance of pro‐and anti‐inflammatory cytokines in patients with CE was revealed, which is the basis for prescribing not only antibacterial therapy, but also local immunomodulatory agents.

Dilawari, A., et al. (2023). "FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 29(19): 3835-3840.
	On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx for treatment of adult patients with folate receptor-α (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic therapies. The VENTANA FOLR1 (FOLR-2.1) RxDx Assay was approved as a companion diagnostic device to select patients for this indication. Approval was based on Study 0417 (SORAYA, NCT04296890), a single-arm, multicenter trial. In 104 patients with measurable disease who received mirvetuximab soravtansine-gynx, the overall response rate was 31.7% [95% confidence interval (CI), 22.9-41.6] with a median duration of response of 6.9 months (95% CI, 5.6-9.7). Ocular toxicity was included as a Boxed Warning in the U.S. Prescribing Information (USPI) to alert providers of the risks of developing severe ocular toxicity including vision impairment and corneal disorders. Pneumonitis and peripheral neuropathy were additional important safety risks included as Warnings and Precautions in the USPI. This is the first approval of a targeted therapy for FRα-positive, platinum-resistant ovarian cancer and the first antibody-drug conjugate approved for ovarian cancer. This article summarizes the favorable benefit-risk assessment leading to FDA's approval of mirvetuximab soravtansine-gynx. (©2023 American Association for Cancer Research.)

Dilbaz, B., et al. (2022). "The effect of hysteroscopic metroplasty on fertility in T-shaped and Y-shaped dysmorphic uterus." The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception 27(5): 384-389.
	Objective: T/Y-shaped dysmorphic uterus is frequently associated with subfertility, abortion, preterm delivery, and recurrent implantation failure. In this study, the impact of hysteroscopic metroplasty for a T/Y-shaped uterus on obstetric outcomes was investigated in patients with infertility and recurrent pregnancy loss (RPL) and compared the uterine anomaly subgroups.; Method: Cases with infertility and/or RPL diagnosed with T/Y-shaped uterus by hysterosalpingography (HSG) and 3D transvaginal ultrasonography (3D TVUSG) with no other male or female pathology have recruited the study. Medical history and the obstetric outcome after two years of follow-up were recorded.; Results: Out of the 92 cases recruited, T-shaped uteri (Group-1) were observed in 30, while 62 (67.3%) patients had Y-shaped uteri. Pregnancy was achieved in 50 (54.3%) of the cases, 28 (56%) of the pregnancies occurred spontaneously, and in 22 (44%) pregnancy was achieved through assisted reproductive techniques (ART). Term delivery occurred in 29 (76.3%) of the pregnancies while 9 (23.6%) had preterm deliveries and a total of 38 (76%) resulted in a live birth. Out of the 31 patients with previous RPL history, 13 (41.9%) achieved pregnancy and 11 out of 13 (84.6%) had a term pregnancy followed by live birth.; Conclusion: Spontaneous pregnancy, and term pregnancy rates after surgery were found to be promising in these uterine anomalies. The pregnancy outcome of the primary infertile patients was found the same in two groups (50%-46.1%), but the results of the RPL patients were found to be better in the T-shaped group than in the Y-shaped group (70%-28.5%).

Dilek, O., et al. (2022). "Impact of the individual counseling program for polycystic ovarya syndrome management among university students: A prospective randomized controlled trial." Nigerian journal of clinical practice 25(6): 809-816.
	Background: Polycystic ovary syndrome (PCOS) is common in women of reproductive age.; Aim: This study aimed to investigate the impact of individual counseling program which had been designed from the transtheoretical model (TM) for students diagnosed with PCOS.; Patients and Methods: The study is a prospective randomized controlled trial. The research was carried out in four stages as screening, diagnosis, randomization, selection, and counseling. The data for the analysis were drawn from a sample of 854 students at first and a total of 67 students were administered the scales. The control (n = 33) and experimental groups (n = 34) were formed based on the simple randomization technique. The sample characteristics were voluntary participation, absence of sexual activity for a minimum of 6 months, belonging to the age group of 19-24, an absence of chronic diseases or any physical disability, and a lack of mental disorders. Participants using medication and obtaining scores of above/below 18.5 and below/above 30 on the body mass index (BMI) were not included in the study.; Results: The prevalence of PCOS among university students was found to be 8.8%. The findings indicated that the majority of the students have been experiencing various physical symptoms such as being overweight, menstrual irregularity, hirsutism, alopecia, acne, and psychological symptoms such as uneasiness, irritability, anger, anxiety, and fatigue. Based on the pretest and posttest scores, it was observed that the anthropometric values and psychological indicators such as the feeling of uneasiness, irritability, anger, anxiety, and fatigue were significantly decreased in the group of PCOS that took the counseling program.; Conclusions: Individual counseling improved the anthropometric measurements and the clinical findings related to PCOS.; Competing Interests: None

Dillon Gabrielle, A., et al. (2022). "Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis." Microvascular research 144: 104421.
	Introduction: Endometriosis is associated with systemic inflammation and increased risk of cardiovascular disease (CVD). Endothelial dysfunction is one of the first manifestations of CVD but is unexplored in women with endometriosis. HMG-CoA-reductase inhibitors (statins) exert potent anti-inflammatory effects, and have been proposed as an adjunctive therapy in women with endometriosis. We hypothesized that microvascular endothelial function would be impaired in otherwise healthy women with endometriosis mediated by reduced nitric oxide (NO)-dependent dilation and that short term statin administration would improve endothelial function.; Methods: In 8 healthy control (HC: 33 ± 9 yr) and 8 women with endometriosis (EN: 34 ± 9 yr), laser-Doppler flux (LDF) was measured continuously during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine (Ach: 10 -10 -10 -1 M) alone and in combination with the NO synthase inhibitor (L-NAME: 0.015 M). 6 EN repeated the microdialysis experiment following 7 days of oral atorvastatin treatment (10 mg). Cutaneous vascular conductance was calculated (CVC = LDF*mmHg -1 ) and normalized to site-specific maximum (28 mM sodium nitroprusside, 43 °C). The NO-dependent dilation was calculated as the difference between the areas under the dose response curves.; Results: Ach-induced vasodilation was blunted in women with endometriosis (main effect p < 0.01), indicating impaired endothelial function. NO-dependent vasodilation was also reduced in women with endometriosis (HC: 217 ± 120.3 AUC vs. EN: 88 ± 97 AUC, p = 0.03). Oral atorvastatin improved Ach-induced (main effect p < 0.01) and NO-dependent (295 ± 153 AUC; p = 0.05) vasodilation in women with endometriosis.; Conclusion: Microcirculatory endothelium-dependent vasodilation is impaired in women with endometriosis, mediated in part by reductions in NO. Short-term oral atorvastatin improved endothelium-dependent vasodilation, suggesting that statin therapy may be a viable intervention strategy to mitigate accelerated CVD risk in women with endometriosis.; Competing Interests: Declaration of competing interest None. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dimas, A., et al. (2023). "The expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review." Przeglad menopauzalny = Menopause review 22(4): 227-235.
	The aim of this systematic review is to investigate the impact of corticotropin-releasing hormone (CRH) family peptides and their corresponding receptors on human physiology and disease onset, with a specific focus on gynaecological malignancies such as breast, endometrial, ovarian, vulvar, and cervical cancer. A comprehensive systematic review of 3 medical databases was conducted by 2 independent reviewers. We reviewed studies that explored the expression and role of CRH peptides in various aspects of cancer biology, in the context of breast, endometrial, ovarian, vulvar, and cervical cancer. Our findings reveal that CRH family peptides and their receptors, CRHR1 and CRHR2, are expressed in diverse gynaecological tissues, including cancer cells. Notably, we observed differential expression patterns among different gynaecological cancer types and stages, indicating potential associations with tumour aggressiveness and patient prognosis. Furthermore, CRH peptides were found to exert significant influences on critical cellular processes, such as cell proliferation, migration, invasion, and immune response, in gynaecological cancers. These findings highlight the multifaceted roles of CRH family peptides in gynaecological malignancies and emphasize the need for further research in this field. Therefore, understanding the mechanisms underlying the involvement of CRH family peptides in tumourigenesis may open new avenues for targeted therapeutic strategies in gynaecological malignancies.; Competing Interests: The authors report no conflict of interest. (Copyright © 2023 Termedia.)

Dimitrios, R., et al. (2021). "Effect of vitamin D supplementation in endometriosis."
	
Ding, N., et al. (2020). "Chinese herbal medicine on treating obese women with polycystic ovary syndrome: A systematic review and meta-analysis protocol." Medicine 99(49): e22982.
	Introduction: Known as an endocrine disorder, Polycystic ovary syndrome (PCOS) has posed an influence on 6% to 20% reproductive females worldwide. The commonly used pharmaceutical agents currently are Oral Contraceptives (OCs) and insulin-sensitizing agents. However, OCs is not appropriate for females pursuing pregnancy. Furthermore, some of insulin-sensitizing agents are found to be related to a high incidence of gastrointestinal adverse effects. In this regard, the effectiveness of Chinese herbal medicine in handling reproductive and metabolic defects simultaneously has been proved by extensive evidence. In this research, the effectiveness and safety of Chinese herbal medicine for obese females with PCOS were examined.; Methods and Analysis: In the systematic review, we searched databases of AMED, Science Online, EMbase, WorldSciNet, the Cochrane Library, PubMed, Nature, MEDLINE, China National Knowledge Infrastructure, the Wanfang Databse and China Biology Medicine Disc and the Chongqing VIP Chinese Science and Technology Periodical Database, to find out the papers published in Chinese or English by September 25, 2020 in this field. In addition, potential reference lists, relevant conference proceedings, qualified studies, related system reviews and other resources were also considered. Two researchers were responsible for independently selecting the research papers, collecting data, and evaluating research quality. Moreover, the data were synthesized with the combination of a fixed-effects or random-effects model with the heterogeneity test. According to the objective and self-reported assessment, the primary outcomes will be Nausea and vomiting were primary outcomes. RevMan 5 software was used to analyze the collected data, the evidence level of which was evaluated by GRADE. The selection between the fixed-effects and random-effects models was determined by the heterogeneity level. In addition to the 95% Confidence Interval (CI), odds ratio (OR), or risk ratio (RR) was applied to the 2 categories. Moreover, 95% CI and standardized mean difference (SMD) or the weighted mean difference (WMD) were taken as the continuous variables. When existing meaningful heterogeneity could not be explained by any assessment such as subgroup analysis, we would not conduct a meta-analysis. During the subgroup analysis, each subgroup in specific cases should be comprehensively considered.; Ethics and Dissemination: The evaluation of rights or personal information of patients was not involved in the systematic review. Hence, we need not gain approval from ethical institutions. This paper will be present at related conferences for communication and published in journals.; Registration: Open Science Framework (OSF) Preregistration: osf.io/yp86h.

Dinoi, G., et al. (2023). "Minimally Invasive Compared With Open Surgery in High-Risk Endometrial Cancer: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 141(1): 59-68.
	Objective: To compare outcomes between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer.; Data Sources: A cohort study of all patients who underwent surgery for high-risk endometrial cancer between 1999 and 2016 at Mayo Clinic (Rochester, Minnesota) and a literature search of MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, and Scopus of all published studies until December 2020.; Methods of Study Selection: The systematic review identified 2,332 patients (14 studies, all retrospective except a subanalysis of a randomized comparison) and the cohort study identified 542 additional patients. Articles were included if reporting original data on overall survival and disease-free survival among patients with high-risk endometrial cancer, defined as International Federation of Gynecology and Obstetrics grade 3 endometrioid, serous, clear cell, mixed histology, or uterine carcinosarcoma. Studies that did not report at least one of the main outcomes, those in which one surgical technique (robotic or laparoscopic surgery) was missing in the comparison analysis with open surgery, and case reports were excluded. Additional data were extracted from a retrospective cohort of patients from Mayo. A random-effect model was used for meta-analysis.; Tabulation, Integration, and Results: This systematic review and meta-analysis was registered in PROSPERO. Literature search and data extraction were performed independently by two reviewers, as well as quality assessment using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and the Newcastle-Ottawa Scale. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Meta-analysis showed that disease-free survival and overall survival in patients with high-risk endometrial cancer who underwent minimally invasive surgery were not statistically different from those of patients who underwent open abdominal surgery (relative risk [RR] 0.93, 95% CI 0.82-1.05, I2 20%, P=.23; and RR 0.92, 95% CI 0.77-1.11, I2 31%, P=.12, respectively). Subgroup analysis by stage (early vs advanced) did not identify a difference between surgical approaches.; Conclusion: Minimally invasive surgery and open surgery had similar disease-free survival and overall survival in patients with high-risk endometrial cancer.; Systematic Review Registration: PROSPERO, CRD42021275535.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Dioun, S., et al. (2022). "COST-EFFECTIVENESS OF HYSTERECTOMY AT THE TIME OF RISK-REDUCING BILATERAL SALPINGOOOPHORECTOMY FOR PATIENTS WITH BRCA1 MUTATIONS." International Journal of Gynecological Cancer 32(Supplement 3): A39.
	Objectives More recent data suggests that patients with BRCA1 are at an increased risk of developing uterine serous cancers. This raises the question of whether a hysterectomy should be done at time of rrBSO. We developed a decision model to compare the cost-effectiveness of rrBSO with or without hysterectomy for patients with BRCA1 mutations. Methods A Markov model was created to simulate the clinical trajectory of a hypothetical cohort of 10,000 women aged 40 years of age with BRCA1 mutations undergoing rrBSO. The initial decision point in the model was whether a hysterectomy was performed at the time of rrBSO. A time horizon of 60 years was used. Postoperative morbidity and mortality were included in the model as well as risk for subsequent hysterectomy and prolapse after hysterectomy. Model probabilities, cost and utility values were derived with assumptions drawn from published literature. The effectiveness was calculated in terms of average quality adjusted life years (QALYs). The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2018 US dollars/QALYs. One way sensitivity analyses were performed to vary the assumptions across a range of plausible values. Results RrBSO with hysterectomy was the least costly strategy at $13,628, followed by rrBSO alone ($14,630). Hysterectomy at time of rrBSO was cost-effective compared with rrBSO. rrBSO alone was subjected to absolute dominance because it was both more costly and less effective. Multiple one-way sensitivity analyses did not substantially impact the costeffectiveness. Conclusions Hysterectomy at time of rrBSO for BRCA1 patients constitutes a cost-effective management strategy.

Dioun, S., et al. (2021). "Cost-effectiveness of dostarlimab in advanced recurrent deficient mismatch repair endometrial cancer patients." International Journal of Gynecological Cancer 31(SUPPL 4): A16.
	Objectives Women with recurrent endometrial cancer who fail carboplatin and paclitaxel have a poor prognosis with few effective options. The recent GARNET Trial showed promising results for dostarlimab in these patients. We developed a decision model to compare the cost-effectiveness of dostarlimab to other treatment options in patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer who have failed first-line chemotherapy. Methods A Markov model was created to simulate the clinical trajectory of women with progressive/recurrent dMMR endometrial cancer who failed carboplatin and paclitaxel (figure 1). The initial decision point in the model was treatment with either dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, cost and utility values were derived with assumptions drawn from published literature. The effectiveness was measured in terms of quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2018 US dollars/QALYs. One-way sensitivity analyses were performed to vary the assumptions across a range of plausible values. Results PLD was the least costly strategy at $54,307, followed by pembrolizumab ($160,780) and dostarlimab ($251,132). PLD was cost-effective compared with dostarlimab with an ICER of $199,621, while pembrolizumab was subjected to extended dominance (table 1). Multiple one-way sensitivity analyses did not substantially impact the cost-effectiveness. Conclusions Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. However, the agent is substantially more costly.

Dioun, S., et al. (2021). "Uptake and Outcomes of Sentinel Lymph Node Mapping in Women With Atypical Endometrial Hyperplasia." Obstetrics and Gynecology 137(5): 924-934.
	Objective: To examine the utilization, morbidity, and cost of sentinel lymph node mapping in women undergoing hysterectomy for complex atypical endometrial hyperplasia.; Methods: Women with complex atypical endometrial hyperplasia who underwent hysterectomy from 2012 to 2018 in the Perspective database were examined. Perioperative morbidity, mortality, and cost were examined based on performance of sentinel lymph node mapping, lymph node dissection or no nodal evaluation.; Results: Among 10,266 women, sentinel lymph node mapping was performed in 620 (6.0%), lymph node dissection in 538 (5.2%), and no lymphatic evaluation in 9,108 (88.7%). Use of sentinel lymph node mapping increased from 0.8% in 2012 to 14.0% in 2018, and the rate of lymph node dissection rose from 5.7% to 6.4% (P<.001). In an adjusted model, residence in the western United States, treatment by high-volume hospitals and use of robotic-assisted hysterectomy were associated with sentinel lymph node mapping (P<.05 for all). The complication rates were similar between the three groups. The median cost for sentinel lymph node mapping ($9,673) and lymph node dissection ($9,754) were higher than in those who did not undergo nodal assessment ($8,435) (P<.001).; Conclusion: Performance of sentinel lymph node mapping is increasing rapidly for women with complex atypical endometrial hyperplasia but is not associated with increased perioperative morbidity or mortality.; Competing Interests: Financial Disclosure Dr. Wright has served as a consultant for Clovis Oncology and received research support from Merck. Dr. Hou has served as a consultant for Foundation Medicine. Dr. Hur has served as a consultant for Kite Pharmaceuticals and has equity in Cambridge Biomedical Economic Consulting Group. The other authors did not disclose any potential conflicts of interest. (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Dioun, S., et al. (2021). "Intraoperative Rupture of the Ovarian Capsule in Early-Stage Ovarian Cancer: A Meta-analysis." Obstetrics and Gynecology 138(2): 261-271.
	Objective: To examine the effects of intraoperative ovarian capsule rupture on progression-free survival and overall survival in women who are undergoing surgery for early-stage ovarian cancer.; Data Sources: MEDLINE using PubMed, EMBASE (Elsevier), ClinicalTrials.gov, and Scopus (Elsevier) were searched from inception until August 11, 2020.; Methods of Study Selection: High-quality studies reporting survival outcomes comparing ovarian capsule rupture to no capsule rupture among patients with early-stage epithelial ovarian cancer who underwent surgical management were abstracted. Study quality was assessed with the Newcastle-Ottawa Scale, and studies with scores of at least 7 points were included.; Tabulation, Integration, and Results: The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between ovarian capsule rupture and oncologic outcomes. Seventeen studies met all the criteria for inclusion in the meta-analysis. Twelve thousand seven hundred fifty-six (62.6%) patients did not have capsule rupture and had disease confined to the ovary on final pathology; 5,532 (33.7%) patients had intraoperative capsule rupture of an otherwise early-stage ovarian cancer. Patients with intraoperative capsule rupture had worse progression-free survival (hazard ratio [HR] 1.92, 95% CI 1.34-2.76, P<.001), with moderate heterogeneity (I2=41%, P=.07) when compared with those without capsule rupture. Pooled results from these studies showed a worse overall survival (HR 1.48, 95% CI 1.15-1.91, P=.003), with moderate heterogeneity (I2=53%, P=.02) when compared with patients without intraoperative capsule rupture. This remained significant in a series of sensitivity analyses.; Conclusion: This systematic review and meta-analysis of high-quality observational studies shows that intraoperative ovarian capsule rupture results in decreased progression-free survival and overall survival in women with early-stage ovarian cancer who are undergoing initial surgical management.; Systematic Review Registration: PROSPERO, CRD42021216561.; Competing Interests: Financial Disclosure Dr. Hou has served as a consultant for Foundation Medicine. Dr. Tergas reports money was paid to her from Auro Vaccines. Dr. Matsuo received an honorarium from Chugai and investigator meeting attendance expense from VBL Therapeutics outside this study. Dr. Wright has served as a consultant for Clovis Oncology, received royalties from UpToDate, and received research support from Merck. The other authors did not report any potential conflicts of interest. (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

DiSilvestro, P., et al. (2023). "Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(3): 609-617.
	Purpose: In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting.; Methods: This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up.; Results: The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; P = .0004 [ P < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups.; Conclusion: Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.

Dizavandi Fatemeh, R., et al. (2019). "An overview of the phytoestrogen effect on vaginal health and dyspareunia in peri- and post-menopausal women." Post Reproductive Health 25(1): 11-20.
	Objective: The aim of this overview was to evaluate the effectiveness of phytoestrogens on vaginal health and dyspareunia in peri- and post-menopausal women.; Material and Methods: Three databases including MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials were from inception to August 2017.; Result: Two systematic reviews and 11 RCTs were included in the overview. According to the findings, isoflavones increased the maturation value and attenuated the vaginal atrophy in the post-menopausal women. Topical isoflavones had beneficial effects on the vaginal atrophy. Similar efficacy was found in Pueraria mirifica and conjugated estrogen cream on dryness ( p = 0.277), soreness ( p = 0.124) and irritation ( p = 0.469), as well as discharge ( p = 0.225) and dyspareunia ( p = 0.089). However, the conjugated estrogen cream was more effective compared to Pueraria mirifica ( p > 0.005) regarding maturation index improvement. Comparison of fennel 5% vaginal cream and placebo gel showed significant difference in superficial cells ( p < 0.01), parabasal cells ( p < 0.01) and intermediate cells ( p < 0.01), whereas no difference was found between the oral fennel and placebo in terms of superficial, parabasal and intermediate cells as well as Maturation value. Administration of 80 mg red clover oil had a significant effect on superficial ( p < 0.005), intermediate ( p < 0.005) and parabasal and vaginal dryness ( p < 0.005) compared to the placebo. Flaxseed had also a trivial effect on maturation value. Genistein had a more prominent effect on the genital score. The severity of dyspareunia decreased by 27%.; Conclusion: Phytoestrogens have various effects based on administration route and type on the vaginal atrophy.

Djusad, S., et al. (2024). "The Use of Vasopressor and Tourniquet to Reduce Hemorrhage during Myomectomy for Uterine Fibroid Removal: A Systematic Review." Open Access Macedonian Journal of Medical Sciences 12(1): 22-28.
	AIM: This review aims to evaluate the efficacy of vasopressin and tourniquet to reduce blood loss during myomectomy for uterine fibroids removal. BACKGROUND: Uterine fibroids and uterine leiomyomata, the most common benign tumors in women, can be difficult for women trying to conceive. Surgical therapy, such as hysterectomy or myomectomy, is one of the main treatment options. Excessive blood loss may occur during the procedure. Clamps or tourniquets around the uterine vessels are commonly used as anti-bleeding precautions during myomectomy. Intra-myometrial injection of vasopressin at the base of the largest fibroids and during hysteroscopic myomectomy is effective in reducing blood loss during laparoscopic myomectomy. METHOD(S): A literature search and computer-aided comprehensive electronic bibliographic search was performed using PubMed, Science Direct, SCOPUS, and Wiley for studies published from January 1997 to November 2017. RESULT(S): Ten studies met the eligibility criteria and were included in this review. Each study assessed and compared the effects of vasopressin to the control group that exerts a hormonal hemorrhagic effect during myomectomy procedures. About 50% of vasopressin hemostatic agents have better outcomes in reducing blood loss. However, the use of both vasopressin and tourniquet simultaneously failed to reduce blood loss. DISCUSSION: Intramyometrial vasopressin injection resulted in a higher efficacy to decrease blood loss during myomectomy. Despite deciding which methods provide the most effective way to decrease blood loss, the two techniques showed excellent outcomes for the quality of the myomectomy procedure itself. CONCLUSION(S): Hemostatic medications have shown to have positive effects on myomectomy patients. The predicted volume of blood loss significantly decreased by both the mechanical tourniquet approach and the injection of the hormone vasopressin.Copyright © 2024 Suskhan Djusad, Ario Bimo, Annisa Futihandayani, Hana Fathia Herianti.

Dmochowski, R. R., et al. (2023). "Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder." BMC Urology 23(1): 64.
	Background: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective beta3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. Method(s): This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults >= 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for >= 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. Discussion(s): OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.Copyright © 2023, The Author(s).

Do, K. T., et al. (2021). "Phase 1 Combination Study of the CHK1 Inhibitor Prexasertib and the PARP Inhibitor Olaparib in High-grade Serous Ovarian Cancer and Other Solid Tumors." Clinical Cancer Research 27(17): 4710‐4716.
	PURPOSE: Checkpoint kinase 1 (CHK1) plays a central role in the response to replication stress through modulation of cell‐cycle checkpoints and homologous recombination (HR) repair. In BRCA‐deficient cancers with de novo or acquired PARP inhibitor resistance, the addition of the CHK1 inhibitor prexasertib to the PARP inhibitor olaparib compromises replication fork stability, as well as HR proficiency, allowing for sensitization to PARP inhibition. PATIENTS AND METHODS: This study followed a 3+3 design with a 7‐day lead‐in of olaparib alone, followed by 28‐day cycles with prexasertib administered on days 1 and 15 in combination with an attenuated dose of olaparib on days 1‐5 and 15‐19. Pharmacokinetic blood samples were collected after olaparib alone and following combination therapy. Patients enrolled to the expansion phase of the study underwent paired tumor biopsies for pharmacodynamic (PD) assessments. RESULTS: Twenty‐nine patients were treated. DLTs included grade 3 neutropenia and grade 3 febrile neutropenia. The MTD/recommended phase 2 dose (RP2D) was prexasertib at 70 mg/m2 i.v. with olaparib at 100 mg by mouth twice daily. Most common treatment‐related adverse events included leukopenia (83%), neutropenia (86%), thrombocytopenia (66%), and anemia (72%). Four of 18 patients with BRCA1‐mutant, PARP inhibitor‐resistant, high‐grade serous ovarian cancer (HGSOC) achieved partial responses. Paired tumor biopsies demonstrated reduction in RAD51 foci and increased expression of γ‐H2AX, pKAP1, and pRPA after combination exposure. CONCLUSIONS: Prexasertib combined with olaparib has preliminary clinical activity in BRCA‐mutant patients with HGSOC who have previously progressed on a PARP inhibitor. PD analyses show that prexasertib compromises HR with evidence of induction of DNA damage and replication stress.

Doan, L., et al. (2023). "Ketamine Analgesia for Long Lasting Pain Relief after Surgery (KALPAS) Study." Cancer Research 83(5).
	Background: Post‐mastectomy pain syndrome (PMPS) affects up to 60% of women undergoing mastectomy. Standard perioperative multimodal analgesia remains only moderately effective in preventing PMPS, and many patients continue to rely on opioids for their chronic pain. In the context of the opioid overdose crisis, alternative interventions are urgently needed. Ketamine targets risks factors for PMPS including acute pain and negative mood, making it an ideal candidate for the prevention of PMPS. Trial Design: This is a multisite, three‐arm, double‐blind, RCT to test the effectiveness of ketamine in reducing PMPS in women undergoing mastectomy for oncologic indication. Arm 1 consists of continuous perioperative ketamine infusion that begins during surgery and continues for 2 hours in the post‐anesthesia care unit (PACU). Arm 2 consists of a single‐dose of ketamine in the PACU given over 50‐60 minutes. Arm 3 consists of placebo. Standard surgical and postsurgical care remain unchanged across all arms. Eligibility Criteria: Inclusion criteria are: women ≥18 years of age undergoing total mastectomy for oncologic indication +/‐ lymph node dissection and +/‐ immediate or delayed reconstruction with no distant metastases. Exclusion criteria include: (1) history of cognitive impairment (2) past ketamine or phencyclidine misuse or abuse, (3) schizophrenia or history of psychosis, (4) history of post‐traumatic stress disorder, (5) known sensitivity or allergy to ketamine, (6) liver or renal sufficiency, (7) uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid disease, or other contraindication to ketamine, (8) lamotrigine alfentanil, physostigmine, or 4‐aminopyridine use, (9) currently pregnant, (10) body mass index greater than 35, (11) non‐English or non‐Spanish speaker, (12) currently participating in another pain interventional trial, (13) patient has started or undergone hormone therapy for gender transition into male, or (14) patient is scheduled for bilateral (or greater) flap reconstruction. Specific Aims: The primary outcome is pain intensity on the Brief Pain Inventory short form scale at the surgical site three months after mastectomy. Secondary outcomes include pain severity and interference at the surgical site, incidence of PMPS, anxiety, and depression over 12 months after surgery. Tertiary outcomes include neuropathic symptoms, fatigue, sleep, physical function, and opioid use. Statistical Methods: We will test the differences in the primary outcome between 1) the continuous ketamine infusion and the control; and 2) the single‐dose ketamine and the control, each at 0.025 significance level (adjusted for multiple comparisons using the Bonferroni correction), based on the two‐sample t‐tests (allowing unequal variances) if outcome variables are approximately normal, or Wilcoxon's rank‐sum tests otherwise. Accrual: The target accrual for this study is ∼750. Recruitment began January 2022. Recruitment is expected to be complete by October 2025. As of July 14, 2022, 43 participants have been enrolled across all sites.

Dobberfuhl, A. D. (2019). "Evaluation and treatment of female stress urinary incontinence after pelvic radiotherapy." Neurourology and Urodynamics 38(S4): S59-S69.
	Introduction: Pelvic radiotherapy is associated with both acute and chronic voiding dysfunction. A review of the success and complications of surgical treatments for female stress urinary incontinence after pelvic radiotherapy has not been summarized in the published literature. Method(s): A systematic review of female stress urinary incontinence after pelvic radiotherapy was conducted using MeSH terminology (1988-2018). Result(s): There is limited published literature on the treatment of stress urinary incontinence in women following pelvic radiotherapy. Long term indwelling urethral catheter should be avoided in all women given the risk of iatrogenic hypospadias. Surgical treatments can be classified into those for the intact versus failed outlet. Urethral bulking injections have been studied in a prospective fashion specifically in women with stress urinary incontinence after radiotherapy and although not randomized, have the highest level of evidence. Patients should be screened for a history of prior radiotherapy before considering sling placement. Artificial urinary sphincter is associated with a high rate of erosion after prior radiotherapy. The role of Burch colposuspension in patients with prior radiotherapy is poorly defined. Urinary diversion should be considered for patients with a devastated outlet. Conclusion(s): Since the long-term effects of radiotherapy on lower urinary tract voiding function are typically irreversible and progressive, further research is needed to mitigate the adverse effects of irradiation and identify more durable treatment options for women with radiation induced bladder dysfunction and stress urinary incontinence.Copyright © 2018 Wiley Periodicals, Inc.

Dobo, N., et al. (2022). "The impact of NOSE colectomy and laparoscopic conventional segmental resection on bowel function and quality of life among patients with rectal endometriosis: prospective randomized trial." Human reproduction (Oxford, England) 37: i111‐i112.
	Study question: What is the impact of laparoscopic conventional or NOSE colorectal resection on bowel function in patients with deep endometriosis infiltrating the rectum one year postoperatively? Summary answer: Both conventional and NOSE colectomy improved the functional outcomes and quality of life among patients with deeply invasive rectal endometriosis one year after bowel surgery. What is known already: Conventional laparoscopic approach to the surgical management of deep endometriosis infiltrating the rectum appears to assure improved digestive functional outcomes. NOSE technique for colorectal disease can significantly reduce the duration of hospital stay, accelerate postoperative recovery with better cosmetic results, and in particular, result in less postoperative pain and fewer complications. However, long‐term solid data about gastrointestinal well‐being after segmental bowel or NOSE resection for deep endometriosis are still missing. Study design, size, duration: Between the 1st September 2019 ‐ 31th of December 2020 we performed a 2‐arm unblinded prospective randomized trial, enroling 91 patients with deep infiltrating rectal endometriosis up to 15 cm from the anal verge. Patients aged between 18 and 45 years, with deep endometriosis infiltrating at least the muscular layer in depth, and up to 50% of rectal circumference, complaining pain, bowel symptoms and/or infertility were included. The average follow up time was 14±2.6 months. Participants/materials, setting, methods: Patients were enroled at Semmelweis University, Department of Obstetrics and Gynecology, Budapest, Hungary and had either conventional laparoscopic bowel resection or NOSE resection. Randomization was performed preoperatively using the simple randomization method. The primary endpoint was to assess the bowel function and quality of life by using the Endometriosis Health Profile 30, the Gastrointestinal Quality of Life Index and the Low Anterior Resection Syndrome score preoperatively, 1 month, 6 months, 1 year after the surgery. Main results and the role of chance: A total of 91 patients were enroled. 39 patients were in the NOSE surgery arm, 49 were in the Conventional laparoscopic surgery arm. One patient was lost to follow‐up and we had two cases of drop out from the trial after randomization due to performing non intended disc resection. This cases were excluded from the study. There was no conversion to laparotomy.The overall scores on Gastrointestinal Quality of Life Index (GIQLI), Low Anterior Resection Syndrome scores (LARS) and Endometriosis Health Profile 30 (EHP30) scores did not reveal significant differences between the two groups. LARS scores were improved, but did not reveal significant differences 12 months (T3) after the operation compared with the preoperative (T0) values in both groups (Conventional surgery group: T0=21.41 T3= 17.90; p=0.934, NOSE surgery goup T0= 26.53 T3= 18.23; p=0.229). GIQLI scores were significantly improved 12 months after the operation compared with the baseline values in Conventional surgery group T0= 95.44 T3= 111.39 p=0.002. EHP30 scores were significantly improved concerning pain, emotion well‐being, control and powerlessness, self‐image, social support and sexuality scale 12 months after the operation compared with the preoperative values in both groups. Limitations, reasons for caution: An obvious bias of performance is the lack of blinding, however blinding was not feasible due to the clinical nature of our study. We report no imprecision in patient selection, but a potential source of attrition bias in our data occured in a total number of three cases in NOSE‐group. Wider implications of the findings: Our study does not show a statistically significant difference between conventional or NOSE surgery for short and mid‐term functional digestive outcomes. Occurrence of longterm bowel dysfunction does not appear to be related to a specific surgical technique.

Dobrindt, E. M., et al. (2021). "Insulinoma in pregnancy (a case presentation and systematic review of the literature)." Rare Tumors 13.
	Insulinomas are rare, benign and functional tumors that coincidentally may become overt during pregnancy or in the post-partum period. As the general symptoms of a pregnancy might cover the clinical presentation, diagnosing remains challenging. We present one additional case of a post-partum insulinoma, combined with a systematic review of the literature to sum up relevant details in diagnosis and treatment. A systematic request of Pubmed/Medline was conducted using the following terms: "insulinoma AND pregnancy" and "insulinoma" for a second request of ClinicalTrials.gov. All publications concerning pregnant or post-partum women with insulinoma were included. Thirty-six cases could be identified for analysis. Each publication was reviewed for demographic, diagnostic and therapeutic data. The most frequent clinical signs were unconsciousness and neurological symptoms. 64.9% were diagnosed during early pregnancy and 35.1% post-partum. 91.9% underwent surgery with a third resected during pregnancy without severe influence on fetal or maternal outcome. Three patients died of metastatic disease or misdiagnosing, two of them miscarried. Insulinoma in pregnancy is rare but should be considered in case of unclear hyperinsulinemic hypoglycemia. Surgery can be performed during the second trimester or post-partum with promising outcome.Copyright © The Author(s) 2021.

Dogra, S., et al. (2023). "Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer." Cancer letters 578: 216437.
	Ovarian cancer (OvCa) has a dismal prognosis because of its late-stage diagnosis and the emergence of chemoresistance. Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase known to regulate cancer cell "stemness", epithelial-mesenchymal transition (EMT), and drug resistance. Here we show that DCLK1 is a druggable target that promotes chemoresistance and tumor progression of high-grade serous OvCa (HGSOC). Importantly, high DCLK1 expression significantly correlates with poor overall and progression-free survival in OvCa patients treated with platinum chemotherapy. DCLK1 expression was elevated in a subset of HGSOC cell lines in adherent (2D) and spheroid (3D) cultures, and the expression was further increased in cisplatin-resistant (CPR) spheroids relative to their sensitive controls. Using cisplatin-sensitive and resistant isogenic cell lines, pharmacologic inhibition (DCLK1-IN-1), and genetic manipulation, we demonstrate that DCLK1 inhibition was effective at re-sensitizing cells to cisplatin, reducing cell proliferation, migration, and invasion. Using kinase domain mutants, we demonstrate that DCLK1 kinase activity is critical for mediating CPR. The combination of cisplatin and DCLK1-IN-1 showed a synergistic cytotoxic effect against OvCa cells in 3D conditions. Targeted gene expression profiling revealed that DCLK1 inhibition in CPR OvCa spheroids significantly reduced TGFβ signaling, and EMT. We show in vivo efficacy of combined DCLK1 inhibition and cisplatin in significantly reducing tumor metastases. Our study shows that DCLK1 is a relevant target in OvCa and combined targeting of DCLK1 in combination with existing chemotherapy could be a novel therapeutic approach to overcome resistance and prevent OvCa recurrence.; Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C·W.H. is an inventor on a patent for nanoparticle-encapsulated DCLK1-targeted siRNAs. C.W.H. is the co-founder of COARE Holdings, Inc. The remaining authors declare that they have no competing interests. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Doi Suhail, A. R., et al. (2020). "Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta-analysis of randomized controlled trials." Obesity reviews : an official journal of the International Association for the Study of Obesity 21(1): e12964.
	Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively. This work assesses the efficacy of metformin in pregnancy to avert one outcome-incident GDM in women at high risk. We included RCTs comparing metformin with usual care or placebo controls in terms of incident GDM and recruiting women at high risk during early pregnancy. Eleven eligible trials enrolled 2370 adult women whose intervention arm consisted of metformin started at conception or before 20 weeks of gestation. Risk of GDM was similar in intervention compared with controls (risk ratio [RR] 1.03; 95% confidence interval [CI], 0.85-1.24). The data were of sufficient quality meeting the criteria for consistency and directness. We conclude that metformin does not contribute to averting the GDM outcome in women at high risk when initiated in pregnancy. The evidence provided by this synthesis affirms that further broad clinical trials investigating this question are no longer needed. (© 2019 World Obesity Federation.)

Doi, T., et al. (2022). "A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors." Cancer Science 113(3): 1010-1017.
	Xentuzumab is an insulin-like growth factor (IGF) ligand-neutralizing antibody. This phase 1 trial assessed xentuzumab in Japanese patients with solid tumors. Patients aged >=20 y old with solid tumors that were refractory or not amenable to standard therapy were enrolled. Patients received xentuzumab intravenously at a starting dose of 750 mg/wk. Dose escalation used a 3 + 3 design with dose de-escalation. The primary endpoint was to determine the maximum tolerated dose (MTD) of xentuzumab. Safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity were also assessed. Fifteen patients received xentuzumab in the dose escalation part (750 mg/wk [n = 6]; 1000 mg/wk [n = 3]; 1400 mg/wk [n = 6]). There were no dose-limiting toxicities at any dose; the MTD of xentuzumab was not reached. Xentuzumab 1000 mg/wk was recommended as the relevant biological dose. Six further patients received xentuzumab 1000 mg/wk in an expansion cohort. Of 21 patients, 13 (61.9%) experienced a drug-related adverse event, most commonly fatigue (23.8%), neutropenia (19.0%), diarrhea, nausea, white blood cell count decrease, and muscle spasms (14.3% each). No relevant deviations from dose linearity of xentuzumab exposure were observed during dose escalation. Total IGF-1 and IGF-2 levels increased and bioactive IGF levels decreased from baseline to 24 h after the first infusion in cycle 1. Partial response was observed in 2 (9.5%) patients with desmoid-type fibromatosis. Disease control was achieved in 6 (28.6%) patients (median duration 42.4 mo). Xentuzumab monotherapy was well tolerated in Japanese patients and showed evidence of anti-tumor activity. This study was registered with www.clinicaltrials.gov (NCT02145741).Copyright © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Dol, J., et al. (2020). "Impact of mobile health interventions during the perinatal period on maternal psychosocial outcomes: a systematic review." JBI evidence synthesis 18(1): 30-55.
	Objective: The objective of this review was to evaluate the effectiveness of mother-targeted mobile health (mHealth) education interventions during the perinatal period on maternal psychosocial outcomes in high-income countries.; Introduction: The perinatal period is an exciting yet challenging period for mothers that requires physical, emotional and social adjustment to new norms and expectations. In recent years, there has been an increase in the use of mHealth by new mothers who are seeking health information through online or mobile applications. While there have been systematic reviews on the impact of mHealth interventions on maternal and newborn health in low- and middle-income countries, the impact of these interventions on maternal psychosocial health outcomes in high-income countries remains uncertain.; Inclusion Criteria: This review considered studies of mHealth education interventions targeting mothers in high-income countries (as defined by the World Bank) during the perinatal period. Interventions must have started between the antenatal period (conception through birth) through six weeks postpartum. All experimental study designs were included. Outcomes included self-efficacy, social support, postpartum anxiety and postpartum depression.; Methods: PubMed, CINAHL, PsycINFO and Embase were searched for published studies in English on December 16, 2018. Gray literature was also searched for non-peer reviewed articles, including Google Scholar, mHealth intelligence and clinical trials databases. Critical appraisal was undertaken by two independent reviewers using standardized critical appraisal instruments from JBI. Quantitative data were extracted from included studies independently by two reviewers using the standardized data extraction tool from JBI. All conflicts were solved through consensus with a third reviewer. Quantitative data were, where possible, pooled in statistical meta-analysis using RevMan. Where statistical pooling was not possible, findings were reported narratively.; Results: Of the 1,607 unique articles identified, 106 full-text papers were screened and 24 articles were critically appraised, with 21 included in the final review. Eleven were quasi-experimental and 10 were randomized controlled trials. The mHealth intervention approach varied, with text message and mobile applications being the most common. Length of intervention ranged from four weeks to six months. The topics of the mHealth intervention varied widely, with the most common topic being postpartum depression. Mothers who received an mHealth intervention targeting postpartum depression showed a decreased score on the Edinburgh Postnatal Depression Scale when measured post-intervention (odds ratio = -6.01, 95% confidence interval = -8.34 to -3.67, p < 0.00001). The outcomes related to self-efficacy, social support and anxiety showed mixed findings of effectiveness (beneficial and no change) across the studies identified.; Conclusions: This review provides insight into the effectiveness of mHealth interventions targeting mothers in high-income countries in the perinatal period to enhance four psychosocial outcomes: self-efficacy, social support, anxiety and depression. Despite a wide variety of outcome measurements used, the predominant findings suggest that there are insufficient data to conclude that mHealth interventions can improve self-efficacy and anxiety outcomes. Potential benefits on social support were related to interventions targeting postnatal behaviors. Postpartum depression was the mostly commonly reported outcome. Findings related to the comparison of pre-post outcomes and intervention versus control demonstrated that mHealth interventions targeting postpartum depression were associated with a reduction in postpartum depression.

Dolan, N., et al. (2022). "Are Mindfulness-Based Interventions as Effective as Cognitive Behavioral Therapy in Reducing Symptoms of Complicated Perinatal Grief? A Systematic Review." Journal of midwifery & women's health 67(2): 209-225.
	INTRODUCTION: Perinatal loss can be a devastating experience for parents that can result in complicated grief symptoms that include depression, anxiety, and posttraumatic stress. Perinatal bereavement care pathways have been developed internationally within health care services; however, there is an apparent lack of recommendations and guidance on grief-focused interventions specifically for complicated perinatal grief. Studies have analyzed the effectiveness of cognitive behavioral therapy (CBT) for perinatal grief, and more recent research has emerged on the use of mindfulness-based interventions (MBIs) for perinatal grief symptoms. The purpose of this study was to conduct a systematic review and present the effectiveness of CBT and MBIs for perinatal grief, to report patient experiences of the interventions, and to determine which intervention can be more effective in managing symptoms of complicated perinatal grief. METHODS: A systematic search was conducted of 5 academic databases: PsycINFO, CINAHL, MEDLINE, Social Science, and ASSIA. No limits on publication date, language, or geographic location were set because of the paucity of research published on this subject. Quality appraisal was conducted for each included study. Findings are reported in accordance with the PRISMA statement. RESULTS: This systematic review identified 8 eligible studies with a total of 681 bereaved participants. The results were examined for effectiveness of CBT and MBIs for grief; effectiveness of CBT and MBIs for depression, anxiety, and posttraumatic stress; and participant experiences. Both interventions produced favorable reductions of perinatal grief symptoms, depression, and posttraumatic stress. However, a true comparison between the 2 interventions' effect on complicated perinatal grief symptoms could not be made because of the limited studies in this area and the heterogeneity of the included studies' methods and outcomes. DISCUSSION: Both MBIs and CBT interventions can be effective in reducing symptoms of complicated perinatal grief. The findings of this review are heavily weighted in quantitative outcome measurements. More qualitative research and randomized controlled trials with larger sample sizes are needed in this area of perinatal bereavement care.

Dolitsky Shelley, N., et al. (2020). "Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review." Menopause (New York, N.Y.) 28(2): 217-224.
	Importance: Menopause is associated with bothersome symptoms for many women, including mood changes, hot flushes, sleep problems, and fatigue. Progesterone is commonly prescribed in combination with estrogen therapy. Although monotherapy with progestins has been used as treatment of menopausal symptoms in women with contraindications to estrogens, the optimal route, and dosage of progestin monotherapy has not been established.; Objective: To assess whether progestin as a standalone treatment is effective for treating vasomotor and mood symptoms associated with menopause.; Evidence Review: We conducted a systematic review using PubMed and Embase databases from January 1980 to January 2020. We included randomized controlled trials (RCTs) that investigated different forms of progestin for the treatment of vasomotor or mood symptoms associated with menopause.; Findings: A systematic search of 892 studies identified seven RCTs involving a total of 601 patients. The available literature was heterogeneous in terms of formulation and dose of progesterone; administration ranged from 5 to 60 mg of transdermal progesterone, 10 to 20 mg oral medroxyprogesterone acetate, and 300 mg of oral micronized progesterone. Duration of treatment also differed between studies, ranging from 21 days to 12 months (median: 12 wks). Three of seven RCTs reported that progestin therapy led to an improvement of vasomotor symptoms (VMS) in postmenopausal women. The largest study administering oral progestin using 300 mg micronized progesterone reported a 58.9% improvement in VMS (vs 23.5% in placebo group, n = 133), whereas the largest study using transdermal progesterone reported no improvement (n = 230). No study reported an improvement of mood symptoms. Side effects, such as headaches and vaginal bleeding, were significant in five of seven RCTs and led to discontinuation of treatment in 6% to 21% of patients.; Conclusions and Relevance: A beneficial effect was reported in some trials with the transdermal route at longer duration and with oral treatment at higher doses for VMS for progesterone-only therapy. This report may help to inform future studies of progestin-only therapy for the treatment of menopausal symptoms.; Competing Interests: Financial disclosure/conflicts of interest: J.H.S. is active on the following boards: the American Society of Reproductive Medicine, The American Board of Obstetrics and Gynecology, the Society for Reproductive Investigation and the American Gynecological and Obstetrical Society. Dr. Segars has received sponsored research funding for clinical trials involving from Biospecifics, Bayer, Allergan, and Abbvie and served as a consultant for Myovant. All other authors have nothing to disclose. (Copyright © 2020 by The North American Menopause Society.)

Dolmans, M. M., et al. (2021). "Conservative management of uterine fibroid-related heavy menstrual bleeding and infertility: Time for a deeper mechanistic understanding and an individualized approach." Journal of Clinical Medicine 10(19): 4389.
	(1) Background: Uterine fibroids are the most common form of benign uterine tumors, causing heavy menstrual bleeding (HMB), pelvic pain, infertility and pressure symptoms. Almost a third of women with uterine fibroids seek treatment. The objective of this review is to understand the mechanisms linking fibroids to these symptoms and evaluate different options for their management, particularly the place of gonadotropin-releasing hormone (GnRH) antagonist. (2) Methods: We gathered the most recent and relevant papers on the main fibroid-related symptoms and medical and surgical therapy for their treatment. Those reporting use of oral GnRH antagonists were investigated in detail. (3) Results: The mechanisms explaining myoma-related HMB and infertility were reviewed, as they are essential to a deeper mechanistic understanding and oriented approach. The choice of treatment depends on the number, size, and location of fibroids, and is guided by the patient's age and desire to preserve her fertility. Economic impacts of myomas in terms of direct costs, lost workdays, and complications were found to be significant. Medical, surgical, and non-surgical strategies were analyzed in this context. Novel medical approaches with GnRH antagonist were explored and found to represent an effective new option. (4) Conclusion(s): The need for alternatives to surgical intervention is very real, especially for women seeking to preserve their fertility. New options now exist, with GnRH antagonists proven to treat fibroid symptoms effectively, opening the door to novel strategies for the management of myomas.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Don Emma, E., et al. (2023). "Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids-A Systematic Review." International Journal of Molecular Sciences 24(8).
	Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.

Donadon, M. F., et al. (2021). "Oxytocin effects on the cognition of women with postpartum depression: a randomized, placebo-controlled clinical trial." Progress in neuro-psychopharmacology & biological psychiatry 111: 110098.
	Background: One of the most common mental disorders in the perinatal period is postpartum depression (PPD), which is associated with impaired emotional functioning due to alterations in different cognitive aspects including thought and facial emotion recognition (FER). Emotional impairments may affect the interaction and care offered to infants and their later development and therefore interventions with potential to minimize impairments associated with PPD are opportune. Oxytocin (OXT) was shown to have therapeutic properties associated with the promotion of affiliative and pro‐social behaviors in different mental disorders. Few studies have assessed its therapeutic potential in PPD. Objectives: To assess the effects of the acute administration of intranasal OXT (24 IU) on FER of baby faces and negative thoughts after delivery in mothers with and without PPD. Methods: We conducted a randomized double‐blind, placebo‐controlled trial with a crossover design involving mothers with PPD (N = 20) and without PPD (N = 35) in the puerperium. Participants completed a static task of FER of baby faces and a questionnaire of post‐natal negative thoughts. Results: Mothers with PPD had increased scores of negative thoughts about motherhood/infants, but no impairments in FER, when compared to healthy mothers. OXT had no effects on the rates of correct judgments or response times in the FER task, but was associated with response biases to facial happiness and the reduction of negative thoughts in mothers with PPD. Discussion/conclusion: OXT may have positive effects on maternal affiliative behavior, maternal care, and mother‐infant interactions as suggested by changes found in different cognitive aspects, thus minimizing the deleterious effects of PPD on child development.

Donatti, L., et al. (2022). "Cognitive Behavioral Therapy in Endometriosis, Psychological Based Intervention: A Systematic Review." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 44(3): 295-303.
	Introduction: Endometriosis is an inflammatory disease that affects women of reproductive age, causing pain and the possibility of infertility. Endometriosis was associated to low life quality and research shows the impact of endometriosis in several areas of life, justifying how these patients are more likely to develop depression, anxiety, and stress.; Objective: The aim of the present systematic review was to explore the field of psychology in endometriosis, identifying studies that used the cognitive behavioral therapy technique as a treatment for endometriosis and chronic pelvic pain.; Methods: The keywords used were Endometriosis and Behavioral Therapy; Behavioral Disciplines and Activities ; Cognitive Behavioral Therapy ; Mental Health ; Psychological Techniques ; Psychology ; Psychotherapy ; Mental Health Services ; and the search was performed in the following databases: PubMed/Medline, Scielo, Lilacs, and Capes. The study followed the PRISMA guidelines and all studies whose intervention strategy used was related to cognitive-behavioral therapy were considered.; Results: Of the 129 articles found, only 5 were selected, and it was possible to identify that the psychological intervention whose approach brought cognitive-behavioral therapy techniques promoted a decrease in the sensation of pain, improvements in the scores of depression and stress, and significant changes in aspects of quality of life such as vitality, physical and social functioning, emotional well-being, control, and autonomy.; Conclusion: Cognitive-behavioral therapy can be very promising to take care of the emotional side of those who have endometriosis However, the present systematic review highlights the need to develop more structured studies with consistent, clear and replicable methods to reach a psychological intervention protocol for patients who live with this gynecological-physical-emotional condition.; Competing Interests: The authors have no conflict of interests to declare. (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Donayeva, A., et al. (2023). "The effects of vitamin D and calcium on primary dysmenorrhea: a systematic review." Journal of medicine and life 16(11): 1597-1605.
	Dysmenorrhea, affecting approximately 80% of adolescents, significantly impairs quality of life, disrupts sleep patterns, and induces mood changes. Furthermore, its economic impact is substantial, accounting for an estimated $200 billion in the United States and $4.2 million in Japan annually. This review aimed to identify the effects of vitamin D and calcium on primary dysmenorrhea. We conducted a comprehensive literature search across Web of Science, PubMed, Scopus, and Science Direct, focusing on studies published from 2010 to 2020. Keywords included 'primary dysmenorrhea', 'vitamin D', '25-OH vitamin D3', 'cholecalciferol', and 'calcium'. The quality assessment of the articles was done using the Consolidated Standards of Reporting Trials (CONSORT) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklists, and the risk bias was assessed using the Cochrane assessment tool. Abnormal low Vit. D levels increased the severity of primary dysmenorrhea through increased prostaglandins and decreased calcium absorption. Vitamin D and calcium supplements could reduce the severity of primary dysmenorrhea and the need for analgesics. This systematic review found an inverse relation between the severity of dysmenorrhea and low serum Vit. D and calcium.. Vitamin D and calcium supplements could reduce the severity of primary dysmenorrhea and the need for analgesics.; Competing Interests: The authors declare no conflict of interest. (© 2023 The Author(s).)

Dondi, G., et al. (2021). "Uterine Preservation Treatments in Sarcomas: Oncological Problems and Reproductive Results: A Systematic Review." Cancers 13(22).
	Uterine sarcomas are rare cancers, sometimes diagnosed in women of childbearing age. Hysterectomy is the standard treatment in early stages. The option of lesion removal to save fertility is described in the literature, but it is still considered experimental. The objective of this systematic review is to report on the available evidence on the reproductive and oncological outcomes of fertility-sparing treatment in women with uterine sarcomas. PubMed, Scopus and Cochrane Central Register of Controlled Trials were searched between 1 January 2011 and 21 June 2021 for publications in English about women with uterine sarcoma treated with a fertility-sparing intervention. Thirty-seven studies were included for a total of 210 patients: 63 low-grade endometrial stromal sarcomas, 35 embryonal rhabdomyosarcomas of the cervix, 19 adenosarcomas, 7 leiomyosarcomas and 2 uterine tumors resembling an ovarian sex cord. Conservative treatment ensured pregnancy in 32% of cases. In terms of oncological outcomes, relapse was related to histology and the worst prognosis was reported for leiomyosarcoma, followed by low-grade endometrial stromal sarcoma, which relapsed in 71% and 54% of cases, respectively. The highest death rate was associated with leiomyosarcoma (57.1%). This study demonstrated that fertility-sparing treatments may be employed in selected cases of early stage uterine sarcoma.

Dong Allan, C., et al. (2020). "Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis." Fertility and Sterility 113(3): 587.
	Objective: To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves outcomes.; Design: Systematic review and meta-analysis.; Setting: University obstetrics and gynecology departments.; Patient(s): Women with RPL and overt/subclinical hypothyroidism, and/or thyroid autoimmunity.; Intervention(s): None.; Main Outcome Measure(s): Associations between RPL and overt/subclinical hypothyroidism and/or thyroid autoimmunity and any effects of treatment.; Result(s): After our review of articles from PubMed, EMBASE, Web of Science, and CENTRAL, we found two interventional studies in which levothyroxine did not improve the subsequent live-birth rate in women with subclinical hypothyroidism with or without thyroid antibodies. A meta-analysis of five studies revealed the prevalence of subclinical hypothyroidism in RPL to be 12.9% (95% confidence interval [CI], 0%-35.2%). A meta-analysis of 17 studies revealed a statistically significant association between RPL and thyroid autoimmunity (odds ratio 1.94; 95% CI, 1.43-2.64). However, a randomized study suggested that levothyroxine does not benefit euthyroid women with thyroid autoimmunity.; Conclusion(s): Based on the limited observational studies available, no association exists between RPL and subclinical hypothyroidism, nor does levothyroxine improve subsequent pregnancy outcomes. An association exists between RPL and thyroid autoimmunity, but levothyroxine does not improve subsequent pregnancy outcomes. Women with RPL should be screened/treated for overt thyroid disease but not thyroid autoimmunity. Thyroid antibody screening is not supported by the published studies, and further randomized studies are needed. No recommendation regarding the treatment of subclinical hypothyroidism can be made at this time; prospective and randomized studies are urgently needed. (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Dong, H., et al. (2021). "Whether preoperative hysteroscopy increases the dissemination of endometrial cancer cells: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 47(9): 2969-2977.
	Aim: To determine whether hysteroscopy (HSC) increases the risk of intraperitoneal dissemination in endometrial cancer patients.; Methods: We conducted a comprehensive review of multiple databases. Quality assessments of eligible studies were performed using the Newcastle-Ottawa and Jadad scales. Positive peritoneal cytology (PPC) as the outcome of interest was compared between endometrial cancer patients with and without HSC. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as a measure of effects.; Results: Three case-control studies and eight retrospective cohort studies included 3364 patients, of whom 1116 underwent preoperative HSC, which resulted in a significantly higher PPC rate (OR, 1.82; 95% CI, 1.31-2.54; p = 0.0004). I 2 was 11%, and the heterogeneity was acceptable. The difference between the groups with stages I-II was statistically insignificant (OR, 1.50; 95% CI, 0.75-2.99; p = 0.25). When liquid was used as the uterine distension medium during HSC and the intrauterine pressure was controlled under 80 mmHg, the difference between the two groups was also insignificant (OR, 1.18; 95% CI, 0.50-2.79; p = 0.71). However, when the intrauterine pressure exceeded 80 mmHg, the difference between the two groups was statistically significant (OR, 2.18; 95% CI, 1.28-3.73; p = 0.004).; Conclusion: This meta-analysis indicates that preoperative HSC in patients with endometrial cancer may increase the risk of intraperitoneal dissemination of malignant cells, which may be associated with intrauterine pressure >80 mmHg but not with stages I-II. There is no reason to avoid HSC for the diagnosis of endometrial cancer, especially in early stages, but intrauterine pressure should possibly be controlled below 80 mmHg. (© 2021 Japan Society of Obstetrics and Gynecology.)

Dong, P., et al. (2021). "Systematic review and meta-analysis of traditional Chinese medicine compound in treating infertility caused by endometriosis." Annals of Palliative Medicine 10(12): 12631-12642.
	Background: To perform meta-analysis to investigate the efficacy and safety of traditional Chinese medicine (TCM) compound in the treatment of endometriosis (EMS)-induced infertility.; Methods: The databases of PubMed, Embase, Cochrane Library, Chinese Journal Full-text Database (CNKI), VIP, Wanfang Science and Technology Journal Full-text Database, and Chinese Biomedical Literature (CBM) were used to search for articles on the treatment of EMS-induced infertility with TCM compound from database establishment to September 2021. Endnote X9 software was used to screen the articles. Stata 15.1 and RevMan 5.3 software were used to record the data, and a meta-analysis was performed on the effective rate, pregnancy rate, abortion rate, incidence of adverse reactions, luteinizing hormone (LH) level, and estradiol (E2) level of TCM compound in the treatment of EMS-induced infertility. Finally, the reliability of the results was assessed by sensitivity analysis. A funnel plot was used to evaluate the publication bias of the articles.; Results: A total of 11 articles were included. Meta-analysis showed that when TCM compound was used to treat EMS-induced infertility, the effective rate of the trial group was significantly higher than that in the control group [odds ratio (OR) =1.26; 95% confidence interval (CI): 1.00 to 1.60; P=0.049], and the difference was statistically significant; the pregnancy rate of the trial group was significantly higher than that in the control group (OR =1.94; 95% CI: 1.50 to 2.50; P<0.05), and the difference was statistically significant; the abortion rate of the trial group was significantly lower than that in the control group (OR =0.16; 95% CI: 0.06 to 0.48; P=0.01), and the difference was statistically significant; and the incidence of adverse reactions in the trial group was not significantly different from the control group (OR =0.48; 95% CI: 0.17 to 1.34; P=0.162); the LH level of the trial and control group [standardized mean difference (SMD) =0.51; 95% CI: -1.73 to 2.75; P=0.658], and the E2 level (SMD =1.65; 95% CI: -0.77 to 4.07; P=0.182) had no statistical difference.; Discussion: Chinese herbal compound is effective in the treatment of endometriotic infertility and has a positive effect on improving the pregnancy rate.

Dong, S., et al. (2019). "Comparative efficacy and safety of traditional Chinese patent medicine for endometriosis: A Bayesian network meta-analysis protocol." Medicine 98(29): e16473.
	Background: Endometriosis is a common disease of women of childbearing age. In recent years, the incidence of endometriosis has been on the rise. The main clinical manifestations are pelvic pain and infertility. In recent years, traditional Chinese patent medicine (TCMP) has played an important role in the treatment of endometriosis. So far, there is a lack of comparison among all the current common TCPMs for endometriosis. Consequently, it is indispensable to propose a network meta-analysis (NMA) protocol to discuss the strengths and weaknesses of different TCMPs.; Methods: We will comprehensively and systematically retrieve the relevant Chinese and English databases from their inceptions to the May 2019. All randomized controlled trials (RCTs) of TCMPs for Endometriosis will be included. Two researchers will independently screen literature, extract data and assess the risk of bias of included studies. We will conduct pairwise meta-analyses and Bayesian network meta-analyses to assess all the available evidence. Data will be analyzed using STATA and WinBUGS software.; Results: This work will compare and rank the relative efficacy of different TCPMs in the treatment of endometriosis in detail.; Conclusion: The results of this study will provide reliable evidence for the selection of clinical treatment program and guideline development.; Prospero Registration Number: CRD42019127781.

Dong, Y., et al. (2020). "A Meta-Analysis on Efficacy and Security of Nedaplatin Versus Cisplatin Combined with Concurrent Radiotherapy for Advanced Cervical Cancer." Anti-Tumor Pharma. 10(4).
	
Dong, Z., et al. (2020). "Immunodiagnosis and Immunotherapeutics Based on Human Papillomavirus for HPV-Induced Cancers." Frontiers in Immunology 11: 586796.
	Infection with human papillomavirus (HPV) is one of the main causes of malignant neoplasms, especially cervical, anogenital, and oropharyngeal cancers. Although we have developed preventive vaccines that can protect from HPV infection, there are still many new cases of HPV-related cancers worldwide. Early diagnosis and therapy are therefore important for the treatment of these diseases. As HPVs are the major contributors to these cancers, it is reasonable to develop reagents, kits, or devices to detect and eliminate HPVs for early diagnosis and therapeutics. Immunological methods are precise strategies that are promising for the accurate detection and blockade of HPVs. During the last decades, the mechanism of how HPVs induce neoplasms has been extensively elucidated, and several oncogenic HPV early proteins, including E5, E6, and E7, have been shown to be positively related to the oncogenesis and malignancy of HPV-induced cancers. These oncoproteins are promising biomarkers for diagnosis and as targets for the therapeutics of HPV-related cancers. Importantly, many specific monoclonal antibodies (mAbs), or newly designed antibody mimics, as well as new immunological kits, devices, and reagents have been developed for both the immunodiagnosis and immunotherapeutics of HPV-induced cancers. In the current review, we summarize the research progress in the immunodiagnosis and immunotherapeutics based on HPV for HPV-induced cancers. In particular, we depict the most promising serological methods for the detection of HPV infection and several therapeutical immunotherapeutics based on HPV, using immunological tools, including native mAbs, radio-labelled mAbs, affitoxins (affibody-linked toxins), intracellular single-chain antibodies (scFvs), nanobodies, therapeutical vaccines, and T-cell-based therapies. Our review aims to provide new clues for researchers to develop novel strategies and methods for the diagnosis and treatment of HPV-induced tumors.© Copyright © 2021 Dong, Hu, Du, Tan, Li, Du, Bai, Ma and Cui.

Donmez, M., et al. (2022). "Efficacy of bright light therapy in perinatal depression: A randomized, double-blind, placebo-controlled study." Journal of Psychiatric Research 149: 315-322.
	Background: Uncertainties and difficulties associated with the current treatment modalities for perinatal depression (PND) may cause some mothers to avoid treatment. Raising awareness about the effectiveness and safety of bright light therapy (BLT) may help to alleviate the challenges of PND. The main goal of this study was to evaluate the efficacy and safety of BLT versus placebo in PND.; Method: A total of 30 women who were either pregnant or in first year postpartum and diagnosed with major depressive disorder were enrolled; 23 completed the study. Patients were randomly assigned to either the BLT (10,000 lux) or placebo (<500 lux) group. BLT and placebo light were applied for 45 min in the morning every day for a 3-week period. The Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAM-D), and Edinburgh Postnatal Depression Scale (EPDS) were administered weekly to evaluate response and remission rates and depression scores.; Results: There was no significant difference between the two groups in terms of baseline depression scores. At the end of the study, the response rates assessed according to MADRS were 75% for BLT and 18.2% for placebo (p = .006), and remission rates were 41.7% vs. 0% (p = .016), respectively. There was no significant difference between the groups (p > .05) in terms of treatment-related side effects. The main limitation of this study is its small sample size, which limits the generalizability of the study's findings.; Conclusion: The results indicate that BLT is more effective than placebo and is reliable in terms of side effects in PND patients. In order to expand the use of BLT in PND, new studies with larger sample sizes are needed. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Donmez, S., et al. (2023). "Analgesic Efficacy of Ibuprofen in Dysmenorrhea." Bezmialem Science 11(2): 163-169.
	Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) are used routinely and as first choice in the analgesic treatment of abdominal pain caused by primary dysmenorrhea (PD). In our study, we aimed to compare the analgesic efficacy of 400 mg and 800 mg ibuprofen doses administered intravenously (iv) in the treatment of patients presenting with abdominal pain due to PD. Method(s): The study was conducted in emergency department over a period of 4 months in a prospective, randomized, controlled and single-blind design. Females aged between 18-50 years were included in the study. The patients were randomly divided into two groups as those who received ibuprofen 400 mg and those who received 800 mg. In these two groups, the pain scores of the patients at 0, 30 and 60 min were determined and analyzed using the 10-unit Numeric Rating Scale (NRS). Result(s): A total of 54 patients, 27 in each group were included in the study. Age, weight and body mass index parameters of the groups were statistically similar. There was no statistically significant difference between the two groups in terms of the degree of pain at admission and at the 30th-60th min of follow-up. In the 400 mg and 800 mg treatment groups, the NRS score differences between 0 and30 min periods [median [interquartile range (IQR): 4 (3-5) and 4 (3-4); p=0.224] and between 0 and 60 min periods [median (IQR): 4 (3-5) and 4 (3-4); p=0.224] were statistically similar. There was no difference between the two groups in terms of need for rescue medication and side effects. Conclusion(s): Similar efficacy is observed in reducing pain intensity between 400 mg and 800 mg doses of iv ibuprofen. According to these findings, it can be concluded that 400 mg of ibuprofen.Copyright © 2023 by the Bezmialem Vakif University.

Donnelly, J., et al. (2022). "Vitamin E in Cancer Treatment: A Review of Clinical Applications in Randomized Control Trials." Nutrients 14(20): 4329.
	Vitamin E, along with other vitamins and micronutrients play a range of physiologic roles in the homeostasis of the body. Moreover, they also have postulated therapeutic roles that are often incompletely studied and understood. In this scoping review, we explored the recent randomized control trials (RCTs) of Vitamin E in the context of cancer, to investigate whether Vitamin E has a therapeutic role. We searched major bibliographic electronic databases to identify sixteen RCTs studying the role of Vitamin E in cancer management that have been published in the last ten years. These studies had different methodological qualities, including some that used Vitamin E in combination with other treatments. Furthermore, due to the heterogenous results, it is difficult to make a consensus statement on the effectiveness of Vitamin E in cancer therapeutics. In some cases, there were even suggestion of detriment with Vitamin E supplementation. Therefore, well designed, large, prospective RCTs are needed studying pure isoforms of Vitamin E to establish the safety and efficacy of this dietary supplement.Copyright © 2022 by the authors.

Donnelly, L. and G. Balneaves Lynda (2022). "Fact or Fiction? The Role of Regulated Body-Identical Hormone Therapy for Menopausal Women." Nursing for women's health 26(2): 143-151.
	Many menopausal women use hormone therapy, including regulated body-identical hormone therapy (rBHT), to relieve vasomotor symptoms and prevent cardiovascular disease. Despite growing interest in rBHT, there is uncertainty regarding potential benefits and risks. With this narrative review, we aimed to synthesize the literature regarding the efficacy of these therapies for managing vasomotor symptoms and preventing cardiovascular disease. Thirteen articles were identified, with authors of several studies showing rBHT and combination therapy (rBHT with synthetic hormone therapy) to be efficacious in managing vasomotor symptoms when compared to placebo. Conflicting evidence exists regarding the efficacy of rBHT in the prevention of cardiovascular disease, with some studies demonstrating improved cardiovascular biomarkers, particularly among women who are at the beginning of the menopausal journey and experiencing symptoms. In summary, rBHT may have a role in the care of women trying to manage vasomotor symptoms and in protecting against cardiovascular disease among menopausal women; however, larger, more rigorously designed randomized controlled trials are required.; Competing Interests: Author Disclosures The authors report no conflicts of interest or relevant financial relationships. (Copyright © 2022. Published by Elsevier Inc.)

Donnez, J., et al. (2022). "Linzagolix With and Without Hormonal Add-Back Therapy for the Treatment of Symptomatic Uterine Fibroids: Two Randomized, Placebo-Controlled, Phase 3 Trials." Obstetrical and Gynecological Survey 77(12): 741-742.
	
Donnez, J., et al. (2022). "Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials." Lancet (London, England) 400(10356): 896-907.
	Background: Uterine fibroids are common non-cancerous neoplasm that cause heavy menstrual bleeding and other signs. Linzagolix is an oral gonadotropin-releasing hormone receptor antagonist taken once per day that dose-dependently suppresses gonadal steroids and might reduce uterine-fibroid-associated signs. Two phase 3 trials were conducted to confirm the efficacy and safety of linzagolix at full-suppression (200 mg) and partial-suppression (100 mg) doses with or without hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate) compared with placebo for the treatment of symptomatic uterine fibroids.; Methods: PRIMROSE 1 and PRIMROSE 2 were identical 52-week, randomised, parallel, double-blind, placebo-controlled, phase 3 trials conducted at clinics in the USA (PRIMROSE 1) and Europe and the USA (PRIMROSE 2). Eligible women with uterine fibroid-associated heavy menstrual bleeding (menstrual blood loss >80 mL per cycle) were randomly assigned in a 1:1:1:1:1 ratio to one of five masked treatments: (1) placebo, (2) 100 mg linzagolix per day alone, (3) 100 mg linzagolix per day with once-per-day hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate), (4) 200 mg linzagolix per day alone, or (5) 200 mg linzagolix per day with once-per-day hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate). The primary endpoint was a response (menstrual blood loss ≤80 mL and ≥50% reduction from baseline) at 24 weeks in women who received at least one dose of treatment and did not meet any exclusion criteria based on predosing assessments. These trials are registered with ClinicalTrials.gov (NCT03070899 and NCT03070951). The trials have been completed.; Findings: Between May, 2017, and October, 2020, in PRIMROSE 1, 574 women were enrolled, of which 48 discontinued and 15 were excluded; therefore, 511 women were included in the full analysis set; and in PRIMROSE 2, 535 women were enrolled, of which 24 did not receive the study drug and ten women were excluded from the study, resulting in 501 women being included in the full analysis set. In both trials, a significantly higher proportion of women had a reduction in heavy menstrual bleeding in all linzagolix (with or without add-back therapy) treatment groups compared with the placebo group (p≤0·003). In PRIMROSE 1, the response rates were 56·4% (95% CI 45·8-66·6%) in the 100 mg group, 66·4% (56·6-75·2%) in the 100 mg plus add-back therapy group, 71·4% (61·8-79·8%) in the 200 mg group, and 75·5% (66·0-83·5%) in the 200 mg plus add-back therapy group, compared with 35·0% (25·8-45·0%) in the placebo group. In PRIMROSE 2, the response rates were 56·7% (46·3-66·7%) in the 100 mg group, 77·2% (67·8-85·0%) in the 100 mg plus add-back therapy group, 77·7% (68·4-85·3%) in the 200 mg group, and 93·9% (87·1-97·7%) in the 200 mg plus add-back therapy group, compared with 29·4% (20·8-39·3%) with placebo. The most common adverse events up to 24 weeks were hot flushes (35% of participants in PRIMROSE 1 and 32% in PRIMROSE 2 with linzagolix [200 mg] alone and 3-14% in all other groups).; Interpretation: Linzagolix (100 mg or 200 mg) with or without add-back therapy significantly reduced heavy menstrual bleeding. Partial suppression with once-per-day linzagolix (100 mg) without add-back therapy potentially provides a unique option for the chronic treatment of symptomatic uterine fibroids in women who cannot or do not want to take concomitant hormonal add-back therapy.; Funding: ObsEva.; Competing Interests: Declaration of interests JD is a member of the scientific advisory board of ObsEva and Preglem. EAS reports institutional grants from the National Institutes for Health related to adenomyosis and from Agency for Healthcare Research and Quality related to uterine fibroids; royalties or licenses from UpToDate; consulting fees from AbbVie, Bayer, Myovant, and ObsEva; honoraria for Continuing Medical Education course presentations from MED-IQ, Physicians’ Education Resource, and WEB MD; and for writt n work from the American College of Obstetricians and Gynecologists and Massachusetts Medical Society; an issued patent (6440445) with no commercial activity; participation in a phase 3 advisory board for Myovant; and is an unpaid advisory board member of the Fibroid Foundation, outside the current work. EM reports National Institute for Health grants paid to the institution; consulting fees from the University of Washington, Pfizer, and Myovant Sciences; and payments or honoraria for MED-IQ, StartART nursing, and Prime Education Continuing Medical Education. DA reports payments to institution from ObsEva and Abbvie; and payments to self from ObsEva and Vindico Medical Education. AA-H reports funding from the National Institutes for Health and consulting fees from Abbvie, Bayer, Myovant, Novartis, ObsEva, and Pfizer, outside the current work. NW reports consulting payments from Abbvie and ObsEva. J-PG is a full-time employee and a stockholder of ObsEva. EB is a full-time employee and a stockholder of ObsEva. AH is a full-time employee and a stockholder of ObsEva. EG is a full-time employee and a stockholder of ObsEva. EL is the founder, a board member, and a stockholder of ObsEva. PT is contracted by Cytel, who received fees from ObsEva for statistical services for the current work and other work. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Donohoe, F., et al. (2021). "The menopause after cancer study (MACS) - A multimodal technology assisted intervention for the management of menopausal symptoms after cancer - Trial protocol of a phase II study." Contemporary clinical trials communications 24: 100865.
	Aims: This study will aim to assess if a composite intervention which involves a specific evidence-based intervention for management of insomnia and non-hormonal pharmacotherapy to manage vasomotor symptoms (VMS) of menopause can improve quality of life for patients experiencing troublesome VMS after cancer who are not eligible for standard systemic menopausal hormone therapy (MHT). Participants will be asked to nominate a partner or companion to support them during this process as an additional form of support.; Background: The menopause transition and its symptoms represent a significant challenge for many patients after cancer treatment, particularly those for whom conventional MHT is contraindicated. These symptoms include hot flushes, night sweats, urogenital symptoms as well as mood and sleep disturbance. These symptoms can exacerbate the consequences of cancer and its treatment.; Methods: We will recruit 205 women who meet inclusion criteria and enrol them on a composite intervention which consists of four parts: (1) use of non-hormonal pharmacotherapy for the management of troublesome vasomotor symptoms of menopause tailored to the timing of predominant symptoms, (2) digital cognitive behavioural therapy for insomnia through the web based Sleepio service, (3) access to information regarding self-management strategies for the common symptoms of menopause and their consequences and (4) identification of a partner or other support person who commits to providing support during the study period.; Outcomes: The primary outcome will be cancer specific quality of life measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). Secondary outcomes will include sleep quality, bother/interference of vasomotor symptoms and communication between couples about their cancer diagnosis and their menopause experience. Sleep will be measured using the Sleep Condition Indicator (SCI) tool, bother/interference of vasomotor symptoms will be measured by the Hot Flush Rating Scale (HFRS) and communication will be measured using the Couples' Illness Communication Scale (CICS). These validated scales will be administered at baseline, four weeks, three months and six months.; Registration: This study is registered on ClinicalTrials.gov with number NCT04766229.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 Published by Elsevier Inc.)

Dorfman, T., et al. (2024). "Proprietary Delivery System Increases Serum Estradiol Levels and Reduces Vasomotor Symptoms in Menopausal Women." Journal of Neurosurgical Anesthesiology 36(1): 1277-1278.
	Objective: Objective: The objective of the study is to demonstrate the benefit of a novel nutraceutical with a proprietary delivery system in decreasing hot flashes in a menopausal population. Initially, two pilot studies were performed in menopausal women utilizing a new supplement regimen delivered by a lozenge using Directline technology. The first study focused on the efficacy of the Directline technology compared to leading competitors. The study showed a greater than 300% peak serum level and a 60% longer peak blood level compared to the market leader's gummy delivery system. The second pilot study demonstrated a significant reduction in the negative symptoms of menopause including hot flashes, insomnia, and irritability. Additionally, serum estradiol levels increased by over 360% in 2 months. Patients also experienced an improvement in dayto- day physical and mental function. Consequently, a much larger IRB-approved and third-party governed study was launched to establish if the supplement system could decrease the incidence of vasomotor symptoms in menopausal women. Design(s): Design: An IRB-approved, open-label study was conducted to evaluate the effectiveness of the supplement system in reducing hot flashes. We included females who had not used hormone therapy in the past 12 months and were currently experiencing hot flashes. The participants were given a 90-day supply of the supplement system, consisting of three lozenges per day. They reported the number of hot flashes and provided feedback on a daily questionnaire. Participants who consented also had four separate blood draws taken (before starting the supplement and every 30 days until the study ended) measuring a variety of hormones and other menopausal parameters. Result(s): Results: The study involves 101 women with a mean age of 53 years old, from various ethnic and socioeconomic backgrounds. To date, 90% of participants reported a reduction in menopausal symptoms, 80% of participants reported a significant reduction in hot flashes and other menopausal symptoms, and 25% of participants reported a complete elimination of hot flashes. Participants also reported improved quality and duration of sleep and increased energy levels. To date, no serious adverse events have been reported. Blood serum is still being collected and analyzed and the study will be completed by September 2023. Conclusion(s): Conclusion(s): In a large population of menopausal women from a multitude of ethnic and socioeconomic backgrounds who utilized our proprietary nutraceutical, hot flashes, and other menopausal symptoms were significantly reduced based on our preliminary data. Additionally, a preliminary assessment of serum estradiol levels shows a significant increase over time as women continue to take the supplement system. The initial data demonstrate a statistically significant benefit based on subjective questionnaire responses and blood serum levels of estradiol proving the efficacy of both the Directline delivery system and the ingredient profile of the supplements.

D'Oria, O., et al. (2024). "Pharmacotherapy for the treatment of recurrent cervical cancer: an update of the literature." Expert Opinion on Pharmacotherapy 25(1): 55-65.
	Introduction: Cervical cancer is the fourth most common cause of cancer-related death worldwide. High-risk locally advanced or recurrent/metastatic cervical cancers have a poor prognosis with routine treatments. The objective of this study is to analyze the data available in the literature on therapies and molecules currently in use to improve the prognosis of recurrent cervical cancer.; Areas Covered: An extensive literature search was conducted by authors to identify relevant trials on various databases. Articles in English published until September 2023 that investigate different pharmacotherapy strategies for the treatment of recurrent cervical cancer, were included. Results of various pharmacological regimens including different combinations of chemotherapy, immune checkpoint inhibitors, DNA damage repair inhibitors and antibody-drug conjugates were analyzed.; Expert Opinion: In recent years, there have been significant improvements in the outcomes of recurrent/metastatic cervical cancer. However, these improvements do not address the unmet need in terms of oncological outcomes. The introduction of immunotherapy and targeted therapies showed advantages in cervical cancer patients. New therapies and combination strategies must be implemented. Centralization of care and enrollment in clinical trials are of paramount importance. Primary and secondary prevention remains the fundamental goal to reduce the burden of cervical cancer.

D'Oria, O., et al. (2022). "The role of preoperative frailty assessment in patients affected by gynecological cancer: a narrative review." Italian Journal of Gynaecology and Obstetrics 34(2): 76-83.
	The following article aims to highlight the importance of the assessment of frailty in patients affected by gynecological cancer and to discuss current data available on scores commonly used to predict adverse postoperative outcomes and overall survival in this group of patients. A narrative review was performed in Medline (PubMed) and Embase database until February 28, 2022. This study includes randomized and observational studies about patients undergoing non-emergent surgery for gynecological malignancies with preoperative frailty assessment. Fourteen studies, for a total of 85957 women, were included. The Modified Frailty Index (mFI) is the most commonly used tool for definition of frail patient. Results highlighted that frail patients had lower disease-free survival rates and overall survival rates than non-frail patients. Additionally, frail patients were more at risk of developing 30-day postoperative complications, non-home discharge and Intensive Care Unit admission than the other group. In gynecologic oncology, the assessment of the state of women's frailty is fundamental to predict adverse outcomes and to customize treatment strategies. Modified Frailty Index is the most used tool to assess the frailty state of gynecologic oncologic patients. We advise that this index should be part of the patients' standard evaluation and that it may be used in the daily practice to aid in shared decision making for tailored therapeutic strategies. In this manuscript we provide an update on the importance of the use of preoperative frailty scores to predict complications among patients treated for gynecological cancer.Copyright © The Authors.

D'Oria, O., et al. (2022). "Fractional Co2 laser for vulvo-vaginal atrophy in gynecologic cancer patients: A valid therapeutic choice? A systematic review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 277: 84-89.
	Introduction: One of the most common adverse events reported by gynecological cancer survivors with spontaneous or iatrogenic menopause is vulvo-vaginal atrophy (VVA). An increasing number of women have this kind of discomfort related to the menopause induced by different cancer therapies. In this regard, fractional CO2 laser may be a valid therapeutic choice for these patients.; Methods: We performed a literature search of PubMed, EMBASE, SCOPUS and Web of Science databases with search terms of laser CO2 treatment of vulvovaginal atrophy and gynecologic cancer survivors and reviewed major US Society Guidelines to create this narrative review of this topic. Breast, ovarian endometrial and cervical cancers were included.; Results: Nine studies were included. Fractional CO2 laser improves clinical symptoms and sexual function, in terms of VHI (vaginal health index) and FSFI (female sexual function index). Non severe adverse event occurred.; Conclusion: According to the best evidence available, fractional CO2 laser treatment for VVA is an effective and safe therapeutic option for gynecological cancer survivors, improving sexual life and quality of life (QoL).; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Dorigo, O., et al. (2023). "Maveropepimut-S, a DPX-Based Immune-Educating Therapy, Shows Promising and Durable Clinical Benefit in Patients with Recurrent Ovarian Cancer, a Phase II Trial." Clinical cancer research : an official journal of the American Association for Cancer Research 29(15): 2808-2815.
	Purpose: Patients with platinum-resistant ovarian cancer respond poorly to existing therapies. Hence there is a need for more effective treatments.; Patients and Methods: The DeCidE1 trial is a multicenter, randomized, open-label, single-arm phase II study to evaluate the safety and effectiveness of maveropepimut-S with cyclophosphamide in patients with recurrent ovarian cancer. Median follow-up for evaluable subjects was 4.4 months. Data were collected from March 2019 to June 2021. Subjects received two injections of 0.25 mL maveropepimut-S 3 weeks apart, followed by one 0.1-mL doses, every 8 weeks up to progression. Oral cyclophosphamide, 50 mg twice daily, was administered in repeating weekly on and off cycles.; Results: Twenty-two patients were enrolled. Median age was 58 years (38-78 years). Among the evaluable population, the objective response rate (ORR) was 21% [90% confidence interval (CI), 7.5%-41.9%], with a disease control rate (DCR) of 63% (90% CI, 41.8%-81.3%), including 4 (21%) patients with partial responses, 8 (42%) stable disease, and 7 (37%) progressive disease. The ORRs were consistent across subgroups based on platinum sensitivity, and DCR was higher in the platinum-resistant subpopulation. Four SD patients maintained clinical benefit up to 25 months. Most treatment-related adverse events (TRAE) were grade 1 and 2 (87% of unique events). Most common AEs were injection site reactions. Eight subjects reported grade 3 and no grade 4 AEs. Survivin-specific T-cell responses were observed in treated patients with clinical benefit.; Conclusions: Maveropepimut-S with intermittent low-dose cyclophosphamide is well-tolerated, with clinical benefit for patients with recurrent ovarian cancer. Observed responses are irrespective of the platinum status. (©2023 The Authors; Published by the American Association for Cancer Research.)

Dorina, G., et al. (2021). "Comparing the efficacy and safety of metformin and inositols in polycystic ovary syndrome: a systematic review and meta-analysis."
	
Dormuth Colin, R., et al. (2021). "Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort." JAMA Network Open 4(4): e215329.
	Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes.; Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations.; Design, Setting, and Participants: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020.; Exposures: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication.; Main Outcomes and Measures: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation.; Results: Data from 456 963 pregnancies were included in this study of fetal death (249 787 [54.7%] in Canada, 197 913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, ≤24 years, 93 201 patients [20.4%]; 25-29 years, 149 117 patients [32.6%]; 30-34 years, 142 442 patients [31.2%]; and ≥35 years, 72 203 patients [15.8%]). Fetal death occurred in 12 907 (7.9%) of 163 810 pregnancies exposed to ondansetron, and 17 476 (5.7%) of 306 766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses.; Conclusions and Relevance: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs.

dos Santos, S., et al. (2024). "Effects of health education on women with urinary incontinence: systematic review and meta-analysis." International Urogynecology Journal 35(2): 273-289.
	Introduction and hypothesis: The objective was to investigate the effects of health education (HE) on urinary symptoms and quality of life in women with urinary incontinence (UI). Method(s): A systematic review and meta-analysis of trials evaluating HE for women with UI. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. Result(s): The search identified 5,118 articles. Eighteen papers were considered eligible. The interventions investigated included health education (HE), combined intervention, self-management (SM), and structured training (ST). Outcomes included quality of life (QoL), UI frequency, UI severity, impression of improvement, incontinence symptoms, urine leakage, fear of leakage, urgency, and incontinence impact. Compared with the control group there was a significant improvement in the frequency, severity, and impact on the QoL for women with UI (assessed by the total score of the International Consultation on Incontinence Questionnaire Short Form (ICIQ SF); RR = -1.47, 95% CI [-2.07, -0.88]; two trials; low certainty of the evidence). Conclusion(s): This review shows that HE seems to be beneficial in the treatment of women with UI when compared with control women (no treatment or general health care), improving the frequency, severity, and impact on QoL assessed by the ICIQ SF total score. However, the certainty of this evidence is low.Copyright © The International Urogynecological Association 2023.

Doty, M. S., et al. (2022). "Daily meditation program for anxiety in individuals admitted to the antepartum unit: a multicenter randomized controlled trial (MEDITATE)." American Journal of Obstetrics & Gynecology MFM 4(3): 100562.
	BACKGROUND: Inpatient antepartum women have higher levels of anxiety than outpatient. Former randomized trials using mindful meditation programs to decrease maternal anxiety have conflicting results; some studies showed a considerable decrease in anxiety levels, whereas others showed no difference. A paucity of trials exist using mindful meditation for maternal anxiety in the inpatient antepartum population; most studies focus on the outpatient clinic population. Because of inpatient acuity and anxiety factors, we conducted a randomized trial to target this population. OBJECTIVE: This study aimed to compare anxiety levels on day 4 of either routine care or routine care plus a twice-daily application-based mindful meditation program in women admitted to the antepartum unit. STUDY DESIGN: In a multisite randomized trial (ClinicalTrials.gov Identifier: NCT03737279), women admitted to the antepartum units were randomized to either routine care plus educational pamphlets (control arm) or routine care plus a twice-daily application-based mindful meditation program (intervention arm). The inclusion criteria were age of at least 18 years, gestational age of at least 23 weeks, planned inpatient care for >3 days from randomization, and care by our university physician team. The primary outcome was maternal state anxiety level (measured using the validated State-Trait Anxiety Inventory) on day 4 (randomization being day 1). The secondary outcomes included stress (measured using the Perceived Stress Scale) and depression (measured using the Edinburgh Depression Scale) on day 4, latency period from randomization to delivery, patient experience, number of meditation sessions, and total meditation time. A total of 56 women were needed for 90% power to detect a decrease in the primary outcome by 30% in the intervention group, compared with the control group. All women were observed using an intention-to-treat analysis. We compared the continuous variables using the Wilcoxon rank-sum test or t test and the categorical variables using the chi-squared test or the Fisher exact test. RESULTS: From March 4, 2019, to December 20, 2019, 412 women were screened for eligibility, 77 women (18.7%) were found eligible, and 56 women (72.7%) were randomized with 28 women in each group. Of note, 96.4% of women completed at least 1 meditation session, and 39.3% of women completed all meditation sessions. The mean score of the anxiety level using the State-Trait Anxiety Inventory on day 4 was not significantly different (P=.24) between the control group (42.0±10.8) and meditation group (37.5±13.1). A decreased anxiety score from day 1 to day 4 was seen in both the control group and meditation group (-4.7 vs -9.4, respectively; P=.12). The rate of abnormal State-Trait Anxiety Inventory scores on day 4 was not significantly different between the control group and meditation group (62% vs 45%, respectively; P=.28). When asked about the experience with the research trial, 88.8% of women in the control group and 89.5% of women in the meditation group reported a positive experience. CONCLUSION: Compared with the control group, a twice-daily application-based mindful meditation program for women admitted to the antepartum unit did not considerably decrease the anxiety score on day 4. However, >88% of women in both groups had a positive experience with the nonpharmacologic intervention.

Dou, P.-H., et al. (2019). "Electrical stimulation on adverse events caused by chemotherapy in patients with cervical cancer: A protocol for a systematic review of randomized controlled trial." Medicine 98(7): e14609.
	Background: This protocol of systematic review aims to investigate the effectiveness of electrical stimulation (ES) on adverse events (AEs) caused by chemotherapy in patients with cervical cancer (CC).; Methods: This systematic review of randomized controlled trials will be identified through searchers of PUBMED, PsycINFO, Scopus, Opengrey, Cochrane Central Register of Controlled Trials, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All the sources will be searched from the inception to the date of study search ran. Additionally, websites of clinical trials registry and reference lists provided in relevant studies and reviews will also be searched. Two independent reviewers will evaluate the eligibility criteria of all potential literature, extract the data, and determine the risk of bias for each included study. RevMan 5.3 software will be used to pool the data and to conduct a meta-analysis.; Results: This systematic review will assess the effectiveness of ES on AEs caused by chemotherapy in patients with CC.; Conclusion: The findings of this study may summarize the latest evidence for the ES on AEs following chemotherapy for CC.; Prospero Registration Number: PROSPERO CRD42019120191.

Dou, Y., et al. (2024). "Long-term outcome and risk factors of reintervention after high intensity focused ultrasound ablation for uterine fibroids: a systematic review and meta-analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 41(1): 2299479.
	Objectives: To quantify the reintervention rate and analyze the risk factors for reintervention after high-intensity focused ultrasound (HIFU) ablation of uterine fibroids.; Methods: Eighteen studies were selected from the seven databases. A meta-analysis was applied to synthesize the reintervention rates for fibroids across various follow-up durations. Subgroup-analysis was conducted based on the year of surgery, sample size, guide methods, and non-perfusion volume ratio (NPVR). Signal intensity of T2-weighted imaging (T2WI) was independently evaluated for reintervention risk.; Results: The study enrolled 5216 patients with fibroids treated with HIFU. There were 3247, 1239, 1762, and 2535 women reaching reintervention rates of 1% (95% confidence interval (CI): 1-1), 7% (95% CI: 4-11), 19% (95% CI: 11-27), and 29% (95% CI: 14-44) at 12, 24, 36, and 60-month after HIFU. The reintervention rates of patients treated with US-guided HIFU (USgHIFU) were significantly lower than those of patients treated with MR-guided focused ultrasound surgery (MRgFUS). When the NPVR of fibroids was over 50%, the reintervention rates at 12, 36 and 60-month after HIFU were 1% (95% CI: 0.3-2), 5% (95% CI: 3-8), and 15% (95% CI: 9-20). The reintervention risk for hyper-intensity fibroids on T2WI was 3.45 times higher (95% CI: 2.7-4.39) for hypo-/iso-intensity fibroids.; Conclusion: This meta-analysis showed that the overall reintervention rates after HIFU were acceptable and provided consultative suggestions regarding treatment alternatives for patients with fibroids. Subgroup-analysis revealed that USgHIFU, NPVR ≥ 50%, and hypo-/iso-intensity of fibroids on T2WI were significant factors in reducing reintervention.; Systematic Review Registration: PROSPERO, CRD42023456094.

Douglas, M. L., et al. (2021). "Efficacy of Advance Care Planning Videos for Patients: A Randomized Controlled Trial in Cancer, Heart, and Kidney Failure Outpatient Settings." Medical decision making : an international journal of the Society for Medical Decision Making 41(3): 292-304.
	BACKGROUND: Patient videos about advance care planning (ACP; hereafter "Videos"), were developed to support uptake of provincial policy and address the complexity of patients' decision-making process. We evaluate self-administered ACP Videos, compare the studies' choice of outcomes, show correlations between the patients' ACP actions, and discuss implications for health care policy. OBJECTIVE: To test the efficacy of the Videos on patients' ACP/goals of care designation conversations with a health care provider. DESIGN, SETTING, AND PARTICIPANTS: Using a 2-arm, 1:1 randomized controlled trial, we recruited outpatients with a diagnosis of kidney failure, heart failure, metastatic lung, gastrointestinal, or gynecological cancer from 22 sites. Analysis followed the intention-to-treat principle. INTERVENTIONS: Videos describing the ACP process and illustrating the resuscitative, medical, and comfort levels of care. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of participants who reported having an ACP/goals of care designation (GCD) conversation with a health care provider by 3 mo. Outcomes were measured using the Behaviours in Advance Care Planning and Actions Survey, an online survey capturing ACP attitudes, processes, and actions. RESULTS: We analyzed 241 and 217 participants at baseline and 3 mo, respectively. The proportion of participants who had an ACP/GCD conversation with a health care provider by 3 mo was significantly different between study arms (46% intervention; 32% control; adjusted odds ratio, 1.83; P = 0.032). Adjusted for the quality of conversations, there was no significant difference. CONCLUSIONS: Videos as stand-alone tools do not engage individuals in high-quality ACP. Pragmatic trials are necessary to evaluate their impact on downstream outcomes when integrated into intentional, comprehensive conversations with a health care provider. Considering the strong correlation between 2 activities (physicians discussing options, patients telling health care providers preferences), policy should focus on empowering patients to initiate these conversations.

Doulgeraki, T., et al. (2023). "The genetic background of female reproductive disorders: a systematic review." Current opinion in obstetrics & gynecology 35(5): 426-433.
	Purpose of Review: Reproductive function is the interplay between environmental factors and the genetic footprint of each individual. The development in genetic analysis has strengthened its role in the investigation of female reproductive disorders, potential treatment options and provision of personalized care. Despite the increasing requirement of genetic testing, the evidence of the gene-disease relationships (GDR) is limited. We performed a systematic review exploring the associations between the most frequent female reproductive endocrine disorders associated with subfertility [including polycystic ovaries syndrome (PCOS), premature ovarian failure (POI) and hypogonadotropic hypogonadism] and their genetic background in order to summarize current knowledge.; Methods: A systematic review of relevant literature in accordance with PRISMA guidelines was conducted until July 2022. Data sources that were used are PubMed and Embase.; Recent Findings: A total of 55 studies were included from the 614 articles identified in the original search. We identified 384 genes associated with one or more of the included female reproductive disorders. The highest number of genes was found to be associated with POI ( N = 209), followed by hypogonadotropic hypogonadism ( N = 88) and PCOS ( N = 87). Four genes, including FSHR , LHβ , LEPR and SF1 were associated with multiple reproductive disorders implying common pathways in the development of those diseases.; Summary: We provide an up-to-date summary of the currently known genes that are associated with three female reproductive disorders (PCOS, POI and hypogonadotropic hypogonadism). The role of genetic analysis in the field of impaired female reproduction may have a role in the diagnosis of female reproductive disorders and personalized patient care. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Douligeris, A., et al. (2023). "The Effect of Postoperative Gum Chewing on Gastrointestinal Function Following Laparoscopic Gynecological Surgery. A Meta-analysis of Randomized Controlled Trials." Journal of Minimally Invasive Gynecology 30(10): 783-796.
	Objective: To assess the effect of postoperative gum chewing on gastrointestinal function in women following laparoscopic gynecological surgery for benign indications. Data Sources: We screened 5 major databases (Medline, Scopus, Google Scholar, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov) from inception till February 2023. Methods of Study Selection: No language restrictions were applied. We included randomized controlled trials comparing the postoperative bowel function between patients who chewed and patients who did not chew gum postoperatively after laparoscopic gynecological procedures for benign indications. Tabulation, Integration, and Results: Data from 5 studies on 670 patients were extracted and analyzed by 3 independent reviewers. Meta-analysis was performed with RevMan 5.4 software (Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2020), with mean differences (MDs), pooled risk ratios, and random-effects model. Postoperative gum chewing significantly reduced the time to first bowel sounds and the time to first passage of flatus (MD -2.58 hours 95% confidence interval (CI) -4.12 to -1.04 p = .001 and MD -3.97 hours 95% CI -6.26 to -1.68 p <.001, respectively). The time to first defecation, the time to first postoperative patients' mobilization, the length of hospital stay, and the risk of postoperative bowel obstruction showed no statistically significant difference between the 2 groups. When subgroup analysis was performed according to the type of the laparoscopic procedure, it failed to reveal a positive impact of postoperative gum chewing in both the times to first passage of flatus and first defecation following laparoscopic hysterectomies (MD -5.35 hours 95% CI -10.93 to 0.23 p = .06 and MD -15.93 hours 95% CI -40.13 to 8.28 p = .20, respectively). Conclusion(s): The results of the present meta-analysis support that postoperative gum chewing following laparoscopic gynecological procedures seems to have a positive effect on the early mobilization of the gastrointestinal tract. However, these results should be interpreted with caution due to the small number of the included randomized controlled clinical trials.Copyright © 2023 AAGL

Doumouchtsis, S. K., et al. (2019). "A systematic review on outcome reporting in randomised controlled trials on surgical interventions for female stress urinary incontinence: a call to develop a core outcome set." BJOG: An International Journal of Obstetrics and Gynaecology 126(12): 1417-1422.
	Background: Several meta-analyses have identified methodological limitations in female stress urinary incontinence (SUI) trials, precluding the synthesis of primary studies and high-quality evidence. Objective(s): Evaluation of outcome measure selection and outcome reporting in randomised controlled trials (RCTs) on surgery for SUI. Search strategy: Systematic review of RCTs identified from bibliographical databases, including Medline, Cochrane, and EMBASE. Selection Criteria: Randomised controlled trials evaluating the efficacy and safety of surgical interventions for the management of female SUI. Data Collection and Analysis: Two researchers independently assessed the included studies and documented outcomes. Main Result(s): Overall, 108 studies were identified that included 422 reported outcomes and 119 outcome measures. The three most common outcomes were cure rates (87 studies), quality of life (85 studies), and overactive bladder (78 studies). The median methodological quality rating was 3 (range 0-3) and the outcome reporting quality rating was 3 (range 0-5). Multinomial logistic regression analysis revealed that the methodological quality and use of validated questionnaire were significant predictors of the quality of outcome reporting (beta = 0.538, P < 0.001; beta = 0.218, P = 0.011, respectively). Conclusion(s): Outcome reporting in SUI trials is highly variable. Until a core outcome set is developed and implemented, we propose an interim use of three commonly reported outcomes in each domain (treatment success rate - complete cure, partial improvement, or failure of response; urodynamic evaluation outcomes - overactive bladder (OAB), voiding dysfunction, and urodynamic stress incontinence; patient-reported outcomes - quality of life, sexual dysfunction, and patient satisfaction) with the use of validated questionnaires for patient-reported outcomes and subjective success rates. Complications should be also explicitly and comprehensively reported using validated outcome measures. Tweetable abstract: There is significant variation in outcome reporting in SUI trials. Our systematic review findings aim to form the basis for the development of a core outcome set.Copyright © 2019 Royal College of Obstetricians and Gynaecologists

Dovnik, A. and F. Dovnik Nina (2020). "Vitamin D and Ovarian Cancer: Systematic Review of the Literature with a Focus on Molecular Mechanisms." Cells 9(2).
	Vitamin D is a lipid soluble vitamin involved primarily in calcium metabolism. Epidemiologic evidence indicates that lower circulating vitamin D levels are associated with a higher risk of ovarian cancer and that vitamin D supplementation is associated with decreased cancer mortality. A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell.; Competing Interests: The authors declare no conflict of interest.

Doxford-Hook Elizabeth, A., et al. (2023). "Management of levator ani avulsion: a systematic review and narrative synthesis." Archives of Gynecology and Obstetrics 308(5): 1399-1408.
	Purpose: Levator ani muscle (LAM) avulsion affects up to 35% of women. Unlike obstetric anal sphincter injury, LAM avulsion is not diagnosed immediately after vaginal delivery, however, has a profound impact on quality of life. The management of pelvic floor disorders is in growing demand yet the significance of LAM avulsion in the context of pelvic floor dysfunction (PFD) is poorly understood. This study collates information on success of treatment for LAM avulsion to establish the best options for management of women.; Methods: MEDLINE ® , MEDLINE ® In-Process, EMBASE, PubMed, CINAHL and The Cochrane Library were searched for articles that evaluated the management techniques used to treat LAM avulsion. The protocol was registered with PROSPERO (CRD42021206427).; Results: Natural healing of LAM avulsion occurs in 50% of women. Conservative measures, including pelvic floor exercises and pessary use are poorly studied. Pelvic floor muscle training for major LAM avulsions was of no benefit. Post-partum pessary use was only of benefit in the first three months for women. Surgeries for LAM avulsion are poorly researched but studies suggest they may provide benefit for 76-97% of patients.; Conclusions: Whilst some women with PFD secondary to LAM avulsion improve spontaneously, 50% continue to have pelvic floor symptoms 1 year following delivery. These symptoms result in a significant negative impact on quality of life, however, it is not clear whether conservative or surgical methods are helpful. There is a pressing need for research to find effective treatments and explore appropriate surgical repair techniques for women with LAM avulsion. (© 2023. Crown.)

Drakopoulou, E., et al. (2022). "Gene Therapy for Malignant and Benign Gynaecological Disorders: A Systematic Review of an Emerging Success Story." Cancers 14(13).
	Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women's life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.

Drexler, U., et al. (2023). "Fasting during cancer treatment: a systematic review." Quality of Life Research 32(5): 1427-1446.
	Background: Clinical data on the modern topic fasting among cancer patients are rare. This review aimed to summarise published clinical data on fasting and its effects on patients undergoing chemotherapy and therefore to give some directions in advising patients with the desire to fast. Method(s): A systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychInfo, CINAHL and Medline) to find studies concerning the use, effectiveness and potential harm of fasting during therapy on cancer patients. The main endpoints were quality of life, side effects and toxicities of the fasting intervention. Result(s): The search results totaled 3983 hits. After systematic sorting according to standardised pre-defined criteria, nine publications which covered eight studies with 379 patients were included in this systematic review. The majority of the patients included were diagnosed with breast- and gynaecological cancers. Fasting duration and timepoints ranged significantly (24-140 h before, and on the day of, chemotherapy to 56 h after chemotherapy). In one study patients were fasting before cancer surgery. The studies were mostly low to moderate quality and reported heterogeneous results. Overall, the studies were insufficiently powered to detect significant effects on the predefined endpoints. Conclusion(s): Fasting for short periods does not have any beneficial effect on the quality of life of cancer patients during treatment. Evidence on fasting regimes reducing side effects and toxicities of chemotherapy is missing. In contrast, as the negative effects of unintentional weight loss are known to impact clinical outcomes severely, fasting is not indicated in this context.Copyright © 2022, The Author(s).

Dreyer, H., et al. (2022). "The Impact of Suppressing Estradiol During Ovarian Stimulation on the Unsupported Luteal Phase: A Randomized Controlled Trial." The Journal of Clinical Endocrinology and Metabolism 107(9): e3633-e3643.
	Context: Supraphysiological sex steroid levels at the follicular-luteal phase transition are implicated as the primary cause of luteal insufficiency after ovarian stimulation (OS) for in vitro fertilization.; Objective: We aimed to determine the impact of suppressing estradiol levels during OS of multiple dominant follicles on the unsupported luteal phase and markers of endometrial maturation.; Methods: At 2 university hospitals, 25 eligible egg donors were randomized to undergo OS using exogenous gonadotropins with or without adjuvant letrozole 5 mg/day. Final oocyte maturation was triggered with a GnRH agonist. No luteal support was provided. The primary outcome was the duration of the luteal phase. Secondary outcomes were luteal phase hormone profiles and the endometrial transcriptomic signature 5 days after oocyte pick up (OPU + 5).; Results: The median (interquartile range [IQR]) luteal phase duration was 8.0 (6.8-11.5) days compared with 5.0 (5.0-6.8) days in the intervention and control group, respectively (P < 0.001). Estradiol levels were effectively suppressed in the letrozole group with a median of 0.86 (0.23-1.24) nmol/L at OPU compared to 2.82 (1.34-3.44) nmol/L in the control group. Median (IQR) progesterone levels at OPU + 5 were 67.05 (15.67-101.75) nmol/L in the letrozole group vs 2.27 (1.05-10.70) nmol/L in the control group (P < 0.001). In the letrozole group, 75% of participants revealed endometrial transcriptomic signatures interpreted as post-receptive. In the control group, 40% were post-receptive and 50% noninformative.; Conclusion: Suppressing estradiol levels in the follicular phase with adjuvant letrozole significantly reduces the disruption of the unsupported luteal phase after OS. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Drks (2021). "„Better with dad" Process and outcome of inpatient-mother-child therapies for postpartum mental disorders: prozess und Outcome stationärer Mutter-Kind: contributing factors and predictors in the field of maternal and paternal relationships." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: Intervention Group (fathers are included in the treatment) The intervention group includes participation in a weekly program (6 sessions of 60‐75 minutes each), accompanying the mothers' treatment on the ward. Part of the intervention are 4 sessions of psychoeducation, an open group session, a father‐child video interaction training, furthermore a 30‐minute individual conversation at the beginning and at the end of the intervention as well as a couple session with the reference therapist of the mother in treatment. Intervention 2: Treatment‐as‐usual (fathers are not included in the treatment) Treatment as usual includes a couple's interview during the course of treatment by the reference therapist of the mother in treatment and participation in a monthly open group for relatives, otherwise no further involvement of fathers in therapy CONDITION: F32.2 ‐ Severe depressive episode without psychotic symptoms F32.3 ‐ Severe depressive episode with psychotic symptoms F33.2 ‐ Recurrent depressive disorder, current episode severe without psychotic symptoms F33.3 ‐ Recurrent depressive disorder, current episode severe with psychotic symptoms F53.1 ‐ Severe mental and behavioural disorders associated with the puerperium, not elsewhere classified F53.8 ‐ Other mental and behavioural disorders associated with the puerperium, not elsewhere classified F53.9 ‐ Puerperal mental disorder, unspecified Mental illness in the postpartum period (0‐2 yrs postpartum) PRIMARY OUTCOME: 1. maternal psychological symptoms compared from start to end of treatment (measured by the Symptom Check List 90); 2. change in mother‐child bonding from start to end of treatment (measured by the CARE Index and the Parental Bonding Questionnaire); 3. change in child developmental age from start to end of treatment (measured by Largo's landmarks); 4. change in paternal distress compared from start to end of treatment (measured by the Gender Sensitive Depression Screening GSDS‐25); 5. change in father‐child bonding (measured by the Parental Bonding Questionnaire). SECONDARY OUTCOME: 1. change in maternal and paternal mentalizing ability (measured by the Parental Reflective Functioning Questionnaire); 2. change of partnership quality from the perspective of mothers as well as fathers (measured by the Partnership Questionnaire PFB‐K); 3. change in parenthood from the perspective of mothers as well as fathers (measured by the "Partnership Questions"); 4. change in social support (measured by the "Fsoz‐U‐K"). INCLUSION CRITERIA: Mothers: ‐ Mental disorder according to ICD‐10 ‐ Indication for mother‐child treatment according to OPS 9‐643 (determined by the ward physician/psychologist) ‐ Birth of a child no longer than 24 months ago ‐ Sufficient German language skills ‐ Written informed consent (DvH, ICH‐GCP), including consent to audio recording of scientific interviews and video recording of mother‐child interactions. Fathers: ‐ Birth of a child no more than 24 months ago. ‐ Admission of the partner with the common child for inpatient mother‐child treatment ‐ Sufficient German language skills ‐ Written informed consent (DvH, ICH‐GCP), including consent to audio recording of scientific interviews and video recording of mother‐child interactions. Children: INCLUSION CRITERIA: ‐ Joint admission with mother for inpatient mother‐child treatment. ‐ Not older than 24 months ‐ No acute stress or illness at the time of videodiagnostic recording

Drks (2021). "Embryo transfer with intrauterine application of human chorionic gonadotropin (hCG) to improve implantation- and pregnancy rates - a randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: Intrauterine application of 500 IU hCG (Pregnyl, ORGANON, Netherlands) dissolved in 40 µl embryo culture medium G‐2™ PLUS (Vitrolife, Sweden) on day 3 after ovum pick up. Intervention 2: Intrauterine application of 500 IU hCG (Pregnyl, ORGANON, Netherlands) solved in 40 µl culture medium (G‐2™ PLUS (Vitrolife, Sweden) on day 5 before embryo transfer Intervention 3: Application of 40µl embryo culture medium without hCG either on day 3 after OPU or on day 5 before embryo transfer (control group) CONDITION: N46 ‐ Male infertility N97 ‐ Female infertility PRIMARY OUTCOME: Implantation rate (number implanted embryos/ number transfered embryos; pregnancy rate: number positive pregnancy tests (beta‐hCG) / number embryo transfers, clinical pregnancy rate: number of verified pregnancy tests by fetal heart beat / number embryo transfers; miscarriage rates: miscarriages/ number of embryo transfers; Live birth rates: number of deliveries / embryo transfers SECONDARY OUTCOME: Miscarriage rate after foetal heartbeat (miscarriages /verfied ckinical pregnancies); Live birth rate (Live birth / embryos transferred) INCLUSION CRITERIA: Included were all fresh blastocyst transfers on day 5 after ovum pick up

Drks (2021). "Influence of additional pelvic floor muscle trainig postpartum on the sexual- and pelvic floor function in primiparous women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: 6 months after delivery additional, professional pelvic floor training for 6 weeks once a week Intervention 2: No additional pelvic floor muscel training CONDITION: O34.8 ‐ Maternal care for other abnormalities of pelvic organs PRIMARY OUTCOME: Influence of pelvic floor training on the pelvic floor, sexuality.; ; Two validated questionnaires 6 and 12 months after delivery in our urogynecology department:; "Female Sexual Function Index ‐ questionnaire" and the "German Pelvic Floor Questionnaire for pregnant women and women after childbirth" SECONDARY OUTCOME: Influence of additional pelvic floor muscle training on clincial parameters, including an evaluation of the degree of a pelvic organ prolaps and the muscel strenght of the pelvic floor muscle. Besides, a gerneral development of pelvic floor function and sexual function in primiparous women after delivery. ; ; Clinical examination with speculum to show a possible pelvic organ prolapse with the help of the POP Q score as well as palpation of the pelvic floor muscle with the help of the Oxford score 6 and 12 months after delivery. INCLUSION CRITERIA: Primiparous women; singleton pregnancy; knowledge of German.

Drks (2021). "Removal of fibromata pendulantia: scissor excision vs. 532 nm-laser." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: excision by scissors We will use both treatment methods on each subject. We will always start with the left side of the body (neck or armpits). The randomised allocation of which procedure we will start with which subject will be done with a computer‐based app called a "random number generator". We will carry out this draw anew for each study participant, so that the persons carrying out the treatment cannot influence which procedure we treat first. Intervention 2: Non‐ablative 532‐nm LBO‐laser CONDITION: D23.9 ‐ Benign neoplasm: Skin, unspecified PRIMARY OUTCOME: Hypothesis: Treatment by the 532 nm LBO laser shows the highest acceptance among the subjects ("Which procedure would you prefer if you were treated again?"). SECONDARY OUTCOME: 1. The treatment with scissors is more painful than the treatment with the LBO laser.; ; 2. The subjects find it an advantage that there is no bleeding with laser therapy and no bandages are needed. ; ; 3. The laser therapy causes less pigment displacement and scars. The cosmetic result is objectively better after 3 months. INCLUSION CRITERIA: 1. The clinical diagnosis is clearly fibromata pendulantia. 2. The patient is at least 18 years old. 3. The patient should be under sixty so that no high‐risk patients have to be called into the doctor's office in times of the COVID‐19 pandemic. 4. The patient is able to understand and sign the patient information sheet and informed consent form. 5. The patient is able to follow all study instructions and attend all study appointments. 6. The patient is not pregnant and does not breastfeed. 7. The patient is in good general health and is free from disease or physical complaints, e.g. other skin diseases, which, in the opinion of the investigator, might interfere with the evaluation of a target lesion or would expose the subject to unacceptable risk by participating in the study.

Drks (2021). "What is the benefit of biofeedback training of the pelvic floor with ACTICORE1® for urinary incontinence?" International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: Biofeedback training with the ACTICORE1 6 minutes a day after inclusion in the study Intervention 2: Biofeedback training with the ACTICORE1 6 minutes a day for 12 weeks after inclusion in the study CONDITION: N39.3 ‐ Stress incontinence N39.4 ‐ Other specified urinary incontinence PRIMARY OUTCOME: ICIQ‐Score 12 weeks after study enrollment SECONDARY OUTCOME: Quality of life according to the EQ‐5D‐3L questionnaire 4 weeks after enrollment; ; Feeling of prolapse 4 weeks after inclusion in the study; ; Impairment of sexuality due to incontinence (VAS) 4 weeks after inclusion in the study; ; Wearing a diaper (yes / no) 4 weeks after enrollment; ; Quality of life according to the EQ‐5D‐3L questionnaire 8 weeks after inclusion in the study; ; Feeling of prolapse 8 weeks after inclusion in the study; ; Impairment of sexuality by the Incontinence (VAS) 8 weeks after Study inclusion; ; Wearing a diaper (yes / no) 8 weeks after enrollment in the course; ; Quality of life according to the EQ‐5D‐3L questionnaire 12 weeks after inclusion in the study; ; Feeling of prolapse 12 weeks after inclusion in the study; ; Impairment of sexuality due to incontinence (VAS) 12 weeks after inclusion in the study; ; Wearing a diaper (yes / no) 12 weeks after enrollment; ; ICIQ‐Score 365 days after study enrollment; ; Quality of life according to the EQ‐5D‐3L questionnaire 365 days after inclusion in the study; ; Feeling of prolapse 365 days after inclusion in the study; ; Impairment of sexuality due to incontinence (VAS) 365 days after inclusion in the study; ; Wearing a diaper (yes / no) 365 days after enrollment INCLUSION CRITERIA: All urinary incontinent patients with subjective impairment and an ICIQ score of greater than or equal to 5 ‐ Vulnerable individuals are also included: Patients with mental illnesses, People with illnesses or disabilities that impair their ability to understand and / or significantly impair their ability to cope with everyday life; pregnant women, patients under 18 years of age (2‐11, 12‐17) and> 65 years of age signed informed consent

Drks (2022). "Evaluation of an app-based self-help training (PandaMom Plus) for the prevention of peripartum mood disorders in women at risk." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: PandaMom Plus: PandaMom Plus is a guided, internet‐based self‐help training offered during the last trimester of pregnancy (> 30th week of pregnancy) and in the first weeks postpartum. The program consists of 12 sessions with the recommendation to use one session per week. Intervention 2: Meine Entspannung (ME): ME is an internet‐based self‐help training focussing on relaxation. CONDITION: Peripartum depression and anxiety PRIMARY OUTCOME: Depression and anxiety scores (EPDS, DASS‐P, Mini‐DIPS) SECONDARY OUTCOME: Program acceptance, adherence INCLUSION CRITERIA: ‐ pregnancy (> 30th week of pregnancy) ‐ EPDS score = 10 (Edinburgh Postnatal Depression Scale; Co Xet al., 1987; German version: Bergant et al., 1998)

Drks (2022). "ViSu - Virtual Reality and Sound Intervention under Chemotherapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention 1: active intervention with VR mindfulness practice of gynecologic and senologic oncology patients while their chemotherapy (ca. 20 minutes each for two cheomtherapy sessions) Intervention 2: receptive music intervention of gynecologic and senologic oncology patients while their chemotherapy (ca. 20 minutes each for two cheomtherapy sessions) Intervention 3: standard care of gynecologic and senologic oncology patients while their chemotherapy (control group) CONDITION: Anxiety, cancer‐related fear of progression C50 ‐ Malignant neoplasm of breast C51 ‐ Malignant neoplasm of vulva C52 ‐ Malignant neoplasm of vagina C53 ‐ Malignant neoplasm of cervi Xuteri C54 ‐ Malignant neoplasm of corpus uteri C55 ‐ Malignant neoplasm of uterus, part unspecified C56 ‐ Malignant neoplasm of ovary C57 ‐ Malignant neoplasm of other and unspecified female genital organs C58 ‐ Malignant neoplasm of placenta PRIMARY OUTCOME: STAI‐State (Staite‐Trait‐Anxiety Questionnaire, Spielberger et al., 1970), before and after intervention SECONDARY OUTCOME: Physiological sympathetic stress response (heart rate/pulse via pulse oximeter in beats per minutes), HPA axis activity (salivary cortisol), progression anxiety (PA‐F‐KF; Mehnert et al., 2006), symptom distress (MIDOS‐2; Stiel et al., 2010), anxiety via visual analog scale (0=not at all anxious to 100=maximally anxious), satisfaction (0=not at all satisfied to 100=maximally satisfied), self‐efficacy expectancy via General Self‐Efficacy Short Scale (ASKU; Beierlein et al., 2014), STAI‐Trait (Grimm, 2009), Demographic & disease‐related data (adapted from PO Bado, Herschbach et al., 2008), Experiences with mindfulness and music, Usability assessment (7 items from the PSSUQ, Lewis, 1995 & self‐created items). INCLUSION CRITERIA: Presence of a confirmed senological and/or gynecological cancer diagnosis Intravenous chemotherapy with an application duration incl. irrigation of at least 60 minutes At least the second chemotherapy session at the time of the intervention Legal capacity Minimum age = 18 years Sufficient knowledge of the German language

Drks (2023). "Adhesion prevention with 4DryField® PH in hysteroscopic surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group 1: Adhesion prevention is performed using 4DryField® PH. The investigational device 4DryField® PH will be applied surgically invasive. The application will be carried out at the end of the intervention. For this purpose, 3 g 4DryField® PH powder will be mixed with 24 ml sterile saline solution, until a uniform gel has been created. Gel will be inserted until the uterine cavity is filled, 24 ml are not necessarily required. Group 2: Untreated control group CONDITION: ; D25 ; N85.6 ; Q51.9 Congenital malformation of uterus and cervix, unspecified Intrauterine synechiae Leiomyoma of uterus N85.6 Q51.9 PRIMARY OUTCOME: The primary endpoint is the adhesion score at second look hysteroscopy. For this purpose, the establish classification system for intrauterine adhesions published by the American Fertility Society (AFS) will be used. SECONDARY OUTCOME: ‐ Individual evaluation of subcategories of primary endpoint ; ‐ Pregnancy rate (in the subgroup of patients wishing to conceive) ; ‐ Frequency of re‐interventions for adhesiolysis ; ‐ Dysmenorrhea ; ‐ If and when normal cycle reoccurs ; ‐ Rate of complications INCLUSION CRITERIA: 1. Hysteroscopic surgery for treatment of intrauterine lesions (septa, myoma, adhesions) with second look hysteroscopy 2. Written consent to participate in the study

Drks (2023). "Hilotherapy for prevention of chemotherapy-induced peripheral polyneuropathy - A unicentric, prospective-controlled, randomized clinical trial for comparison of local hilotherapy vs. no therapy to prevent peripheral polyneuropathy during Taxan-based chemotherapy regimen." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group 1: no hilotherapy of hands and feet Group 2: hilotherapy of hands and feet CONDITION: ; G62.0 ; C50.9 ; C54 ; C56 ; C53 Breast, unspecified C50.9 Drug‐induced polyneuropathy G62.0 Malignant neoplasm of cervi Xuteri Malignant neoplasm of corpus uteri Malignant neoplasm of ovary PRIMARY OUTCOME: The primary endpoint of this study is the comparison of the incidence of a peripheral polyneuropathy (clinical Total Neuropathy Score cTNS = 11) in patients with gynecologic malignoma that are undergoing Taxan‐based chemotherapy regimen with or without a preventive hilotherapy of hands and feet.; Study visits will take place at the beginning, in the middle and at the end of the planned chemotherapy regimen.; Additionally, two follow‐up visits will take place six months and twelve months after the end of chemotherapy. SECONDARY OUTCOME: * Subjective extent of CIPN as measured with the EORTC QLQ‐CIPN20 questionnaire. ; * Changes in the result of electrophysical examinations before and after chemotherapy. ; * Acceptance of hilotherapy measured as the amount of patinets that have to stop local cold application during a session (> 5 miutes) or terminate earlier ir stop the treament completely for the rest of chemotherapy. ; * Adverse effects of hilotherapy documented as any adverse event. ; * Tolerance of chemotherapy measured as the proportion of patient with dose reduction or premature end of chemotherapy. ; * Quality of Life of patients measured with the EORTC QLQ‐C30 questionnaire ; * Comparison of the time of regression, cTNS score of persisting symptoms and amount of patients without residues after end of chemotherapy and follow‐up between patients with and without preventive hilotherapy. INCLUSION CRITERIA: * Written consent for participation in this trail * Age =18 years * Female * Breast or genital cancer of the woman * Planned application of a Taxan‐based chemotherapy regimen (Paclitaxel, Nac‐Paclitaxel) independent of the therapy line * Taxan‐ and Platin‐naivity * Sufficient knowledge of the German language to assure an adequat survey of patient's history

Drks (2023). "PET-guided Radiosurgery of Oligometastatic Cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group 1: A planning CT with a PET/CT or integrating a PET/MRI is obtained. Patients with 2 to 5 extracranial metastases with or without 1 to 3 cerebral metastases are treated with a single fraction per lesion of radiotherapy on 1 to 3 working days with 20 to 24 Gy. Systemic chemotherapy starts within three weeks after the end of radiotherapy according to guidelines. Group 2: A planning CT with a PET/CT or integrating a PET/MRI is obtained. Patients with 2 to 5 extracranial metastases with or without 1 to 3 cerebral metastasis are treated with three fractions of 10 to 14 Gy per lesion within a maximum of eight working days. The mean dose to the GTV should exceed 100 BED. Systemic chemotherapy starts within 2 weeks after the end of radiotherapy according to guidelines. CONDITION: Oligometastasis wth two to five extracranial and not more than three ZNS lesions PRIMARY OUTCOME: progression‐free survival SECONDARY OUTCOME: overall survival ; time to retreatment INCLUSION CRITERIA: ICD‐10: C00‐25, C30‐34(NSCLC only), C37, C39, C44‐45, C48, C50 (hormone‐resistant only), C51‐58, C60‐61 (castration‐resistant only), C63‐69, C73‐74, and C80 oligometastatic disease with =5 extracranial lesions and =3 intrecebral lesions wihtout presious treatment, after relapse after complete remission or partial remission patient qualifies for cytotoxic systemic therapy normal blood counts (Hb>8g/dl, ANC>1500/mm³, thrombocytes >100 000/mm³) normal liver function tests (ASAT/ALAT/AP=2.5*ULN), if liver metastatic and to be treated: <5*ULN Bilirubin <1,5*ULN Creatinin clearance (Cockroft‐Gault) > 50 ml/min ability to understand research protocol and willing to comply with reassessments and follow‐ups consent to have the patient’s case re‐discussed in interdisciplinary tumor boards. negative pregnancy test for female patients aged <50 yrs. if sexually active, ability to use pregnancy prevention methods until 12 months after endin

Drost Larissa, E., et al. (2023). "A web-based decision aid for shared decision making in pelvic organ prolapse: the SHADE-POP trial." International Urogynecology Journal 34(1): 79-86.
	Introduction and Hypothesis: Among women worldwide, pelvic organ prolapse (POP) is a common problem. There are three different treatment options for POP: pelvic floor muscle therapy, pessary treatment and prolapse surgery. As none of the three treatment options is clearly superior, shared decision making (SDM) is very important. A decision aid (DA) is known to facilitate patient participation and SDM. We hypothesise that the use of a web-based DA for POP increases patients' satisfaction with information and care and reduces decisional conflict.; Methods: This two-arm, multicentre, cluster randomised controlled trial was performed in women with POP in five different Dutch hospitals. The control group received usual care (UC) and the intervention group received the DA in addition to UC. Primary outcome measures were satisfaction with treatment decision making and satisfaction with information. Analyses were performed using independent sample t tests, Chi-squared tests, and multilevel linear regression analyses.; Results: Between the DA group (n=40) and the UC group (n=56) no differences were found concerning patients' satisfaction with information, with scores of 45.63 and 46.14 out of 50 respectively (p=0.67). Also, no differences were found concerning the perceived role in decision making, as patients scored 46.83 in the DA group and 46.41 in the UC group, out of a maximum of 54 (n=0.81).; Conclusions: No differences were found concerning patients' satisfaction with information and treatment decision making between the DA and UC. However, both groups scored high on the questionnaires, which suggests that the decision process is already of high quality. (© 2022. The Author(s).)

Du, H. L., et al. (2021). "Meta-analysis of Kushen Gel combined with antifungal drugs in treatment of vulvovaginal candidiasis." Chinese Traditional and Herbal Drugs 52(16): 4973-4985.
	Objective: To systematically evaluate the clinical efficacy and safety of Kushen Gel () combined with antifungal drug in the treatment of vulvovaginal candidiasis (VVC). Method(s): The PubMed, Web of Science, Embase, Cochrane Library, Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), VIP, Wanfang Database were electronically searched to collect randomized controlled trials (RCTs) on Kushen Gel combined with antifungal drug in the treatment of VVC. The retrieval time was from database establishment to May 31, 2021. The literatures, extracting data, the quality of the included studies were screened and evaluated based on Cochrane's systematic evaluation principles. RevMan 5.3 software was used for Meta-analysis. Result(s): A total of 34 RCTs involving 3272 subjects were included. Meta-analysis results showed that in the patients with VVC, compared with antifungal drug alone, combination of Kushen Gel with antifungal drug can significantly increase the negative conversion rate of Candida [RR=1.20, 95% CI (1.17, 1.24), P < 0.000 01], reduce the recurrence rate of VVC [RR=0.25, 95% CI (0.17, 0.35), P < 0.000 01]. In additon, combination with Kushen Gel is superior to monotherapy with antifungal drug in improving vaginal itching [MD=-3.34, 95% CI (-3.54, -3.15), P < 0.000 01], vaginal pain [MD=-2.66, 95% CI (-3.16, -2.17), P < 0.000 01], abnormal leucorrhea [MD=-2.87, 95% CI (-3.13, -2.67), P < 0.000 01], and vaginal mucosal hyperemia [MD=-3.60, 95% CI (-4.02, -3.18), P < 0.000 01] symptoms. Otherwise, no statistically significant difference in adverse reactions rate were found between the two groups [RR=0.86, 95% CI (0.29, 2.49), P=0.78]. Conclusion(s): In the patients of VVC, Kushen Gel combined with antifungal drug can effectively increase the negative conversion rate of pathogenic bacteria, reduce the recurrence rate, and accelerate the relief of clinical symptoms, which is superior to that of antifungal drug alone. And the combination regimen is safe in clinical application.Copyright © 2021, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Du, J., et al. (2020). "The effect of icariin for infertile women with thin endometrium: A protocol for systematic review." Medicine 99(12): e19111.
	Background: Thin endometrium, defined as <7 mm of the endometrial thickness around ovulation period, had been identified as a negative factor on pregnancy rate of infertile women. It was considered to be the toughest part in treatment of infertility, because there was a lack of significant effect, although many drugs had been already used. Icariin was one of the major bioactive pharmaceutical constituent extracted from the Chinese herb "Ying Yang Huo," in the genus of Epimedium, and some randomized controlled trials reported its application for thin endometrium. There is no systematic review focusing on the effective of icariin in treating infertile women with thin endometrium, so our review aims to explore it.; Methods: The bibliographic database and electronic library will be systematically searched online, such as MEDLINE, EMBASE, Web of Science, Clinicaltrails.org., China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, and Cochrane Library. And the reference listed for potential literatures of included studies will be scanned additionally. Related randomized controlled trials (RCTs) will be collected and selected before January 4, 2020. Trials will be screened by independent reviewers, and the literature will be search in English or Chinese, with the search terms as "Icariin," "Epimedium," "infertile women," "female infertility," "endometrium," "pregnancy rate." The software for Systematic review and Meta-analysis is RevMan 5.3. The protocol and the systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement.; Result and Conclusion: The efficacy of icariin to treat thin endometrium will be evaluated, and the conclusion will be published to help clinicians determine treatment strategy for infertile women with thin endometirum by providing medical evidence.; Registration Information: PROSPERO CRD42019148977.

Du, J., et al. (2020). "Efficacy and safety of platelet-rich plasma for the treatment of thin endometrium: A protocol for systematic review and meta-analysis." Medicine 99(3): e18848.
	Background: Endometrial thickness has been identified as a prognostic factor for pregnancy rate for patients with female infertility. Thin endometrium is defined as <7 mm on the day of ovulation, or on the day of human chorionic gonadotrophin (HCG) injection in fresh in vitro fertilization (IVF) cycles, or the day to start progesterone in frozen-thaw embryo transfer cycles, as stated in the guideline of thin endometrium from the Canadin Fertility and Andrology Society and Chinese expert consensus from the Society of Reproductive Medicine, Chinese Medical Association. Many medicines are used for improving the endometrial thickness and embryo implantation rate of the patients with thin endometirum, but thin endometrium remains a major troublesome clinical problem with limited efficacy.Platelet-rich plasma (PRP), as a growing and robust therapeutic option in musculoskeletal medicine, is a preparation of autologous plasma with a high concentration of platelets, and the therapeutic mechanism is based on the capacity to supply supra physiologic amounts of essential growth factors to provide a regenerative stimulus for promoting repair in tissues with low healing potential. Some randomized controlled trials have reported the application of PRP for patients with thin endometrium with satisfactory effect. However, there is no systematic review on efficacy and safety of PRP as a treatment of thin endometrium.; Methods: The data and information will be retrieved from the databases of MEDLINE, Embase, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database, Wan Fang Database, China National Knowledge Infrastructure Database, VIP Science Technology Periodical Database, and OpenGrey for gray literature. The randomized controlled clinical trials are going to be selected before December 20, 2019, in English or Chinese language, with the search terms including "thin endometrium,""platelet-rich plasma," "endometrial thickness," "hemorheology of endometrium," "pregnancy rate," and "adverse reactions." RevMan 5.3 will be used for systematic review and meta-analysis. This protocol will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and the systematic review will be reported with the PRISMA statement.; Results and Conclusion: The efficacy and safety of PRP for the treatment of thin endometrium will be evaluated, and the conclusion will be published to provide medical evidence for a better clinical decision of patients with thin endometirum.

Du, S., et al. (2023). "Systematic review and meta-analysis of moxibustion on urinary incontinence among women." World Journal of Acupuncture - Moxibustion 33(4): 314-324.
	Background: Urinary incontinence (UI) is a common condition that bothers women's lives, including stress urinary incontinence (SUI), urgency urinary incontinence (UUI) and mixed urinary incontinence (MUI). The current non-surgical treatment of Western medicine includes pelvic floor muscle training (PFMT), medication, electric stimulation, etc., all of which have varied limitations. For instance, the patients are poor in compliance with PFMT and medication results in frequent adverse effects. Being one of the featured treatments of TCM, moxibustion has several merits including safety, low cost and simple operation. In recent years, the clinical evidences prove increasingly that moxibustion may be effective for women with UI. However, there is no high-quality systematic review of moxibustion for this disease. Objective(s): To evaluate the effect and safety of moxibustion on UI (including SUI, UUI and MUI) among women. Method(s): From the inception to October 13, 2022, the data of the randomized controlled trials (RCTs) of moxibustion on UI among women were collected from CNKI, WanFang Data, VIP, SinoMed, Web of Science, Pubmed, EMBASE and Cochrane Library databases. Two investigators screened the articles independently and extracted the data according to the inclusion and exclusion criteria developed in advance. Using the risk of bias assessment tool of Cochrane Handbook, the included RCTs were evaluated. With RevMan 5.3 software, meta-analysis was performed, and the GRADE tool was adopted to assess evidence certainty of different outcomes. Result(s): A total of 1176 articles were retrieved and 19 of them with 1397 patients were eligible and included in the review. In experimental groups, moxibustion combined with PFMT was used, while in control groups PFMT was applied alone. And the subjects were all women with SUI. Meta-analysis showed that compared with PFMT alone, moxibustion combined with PFMT reduced the urine leakage volume (1-hour pad test) (MD = -1.95g, 95%CI [-2.32, -1.57], P < 0.001), the frequency of UI in 24-hour (MD = -0.64, 95%CI [-0.88, -0.40], P < 0.001) and the score of the short form of International Consultation on Incontinence Questionnaire (ICIQ-SF) of women with SUI (MD = -2.53, 95%CI [-3.43, -1.63], P < 0.001); and this combined intervention measure did not increase significantly the adverse events (RR = 0.82, 95%CI [0.15, 4.6], P = 0.82). GRADE assessment showed that the UI frequency in 24-hour and the incidence of adverse events were rated as low quality, the urine leakage volume of 1-hour pad test and ICIQ-SF score were very low quality. Conclusion(s): Compared with PFMT alone, the intervention combined with moxibustion greatly reduced the urine leakage volume and UI frequency and improved the quality of life (QoL) among women with SUI with favorable safety. Moxibustion could be effective supplementary therapy on SUI among women. However, due to the high risk of bias of the included trials and low certainty of evidence, more high-quality clinical studies are needed to verify the above findings. Registration: Registered on PROSPERO: CRD42022297643.Copyright © 2023

Du, X., et al. (2024). "Clinical Study of Deep Hyperthermia Combined with Computational Medicine of Platinum Chemotherapy in the Treatment of Ovarian Cancer." Alternative Therapies in Health and Medicine.
	Objective: Deep hyperthermia combined with platinum-based chemotherapy (DHCT) might lead to the development of better therapeutic strategy for patients with malignant tumor. This study aimed to analyze the computational medical differences in ovarian cancer patients treated with DHCT compared with platinum-based chemotherapy alone. Method(s): 78 patients with advanced ovarian cancer admitted from November 2017 to November 2021 were randomly selected as subjects. Overall survival analysis and CA125 clinical efficiency evaluation were performed to explore the effect of DHCT on cis-platinum therapy. All patients were informed and consented, and approved by the hospital committee. The data were systematically analyzed by chi-squared test to analyze clinical effect and safety observation, and the Kaplan-Meier method and log-rank test were used for survival analysis. Result(s): Survival analysis showed that DHCT was strongly associated with improved overall survival (OS) in the platinum treatment of ovarian cancer patients (Hazard Ratio = 1.57, 95% CI: 0.93-2.44, P = .017). For ovarian cancer patients receiving lobaplatin treatment, DHCT could also elevate their survival (Hazard Ratio = 1.52, 95% CI :1.02-2.25, P = .013). The study also showed a statistically significant difference in clinical outcomes between the two groups (P < .001), and the opposite is true for adverse reactions. Conclusion(s): Our results suggest that DHCT is expected to be combined with platinum chemotherapy, which is helpful for the molecular classification of ovarian cancer patients. More studies are needed to further verified the clinical significance.

Duan, X., et al. (2021). "Effect of metformin on adiponectin in PCOS: A meta-analysis and a systematic review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 267: 61-67.
	Background: Conflicting results have been reported regarding the effect of metformin on adiponectin levels in women with polycystic ovary syndrome (PCOS). This meta-analysis reviewed all studies comparing adiponectin levels before and after metformin treatment in PCOS women. Additionally, changes in other indicators, including long-term complications associated with PCOS, such as inflammatory, metabolism factors and hormonal profile, were investigated following metformin treatment. We conducted subgroup analysis based on body mass index (BMI) stratification and appropriate pooling.; Methods: We searched literature in PUBMED, EMBASE, the Cochrane Library, and CNKI databases. The main meta-analysis included 11 studies containing data on 353 subjects.; Results: Metformin treatment was associated with significantly increased serum adiponectin concentrations [10 studies, random-effects SMD (95% CI) -0.58 [-1.03, -0.13]; I 2 = 86%; P = 0.01]. Additionally, the meta-analysis revealed that circulating tumor necrosis factor-α(TNF-α) and C-reactive protein (CRP) concentrations were significantly decreased after metformin treatment, with corresponding SMDs of 1.01 (95% CI: 0.74-1.28, P＜0.00001) and 0.48(95% CI: 0.35-0.60, P＜0.00001).; Conclusion: Following metformin administration, serum adiponectin concentrations of PCOS women were found to be significantly increased, accompanied by a significant improvement in other indicators. Further investigation with a larger sample size should be conducted to validate optimal dose and duration of metformin.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Duarte Pablo, R., et al. (2022). "Quality of life analysis measured with the Cervantes 16 scale in treated menopausal women with genitourinary syndrome." Journal of comparative effectiveness research 11(18): 1365-1374.
	Aim : To assess the quality of life of menopausal women with genitourinary syndrome receiving local drugs (prasterone, estriol or promestriene). Methods : Prospective, longitudinal, randomized study in which quality of life was assessed using the 16-item Cervantes scale (EC16) before and after treatment. Results : A total of 45 women were assessed (35.6% received prasterone, 33.3% estriol and 31.1% promestriene). After treatment, statistically significant mean score differences were observed in EC16, mainly with prasterone. Improvement in EC16 score only shows a statistically significant relationship with age and drug use. Conclusion : The EC16 is an affordable and quick-to-apply tool that allows physicians and patients to know patients' self-perceived quality of life. Local treatment has been shown to improve the quality of life of menopausal patients with genitourinary syndrome.

Dube, R. and S. Kar Subhranshu (2022). "Genital Microbiota and Outcome of Assisted Reproductive Treatment-A Systematic Review." Life (Basel, Switzerland) 12(11).
	The balance between different bacterial species is essential for optimal vaginal health. Microbiome includes the host genome along with microorganism genomes and incorporates the biotic and abiotic factors, reflecting the habitat as a whole. A significant difference exists in the composition and number of the human microbiota in healthy individuals. About one-tenth of the total body microbiota exists in the urogenital tract and these can be identified by microscopy and culture-based methods, quantitative PCR, next generation and whole genome sequencing. The trend of delaying the planning of pregnancy to a later age nowadays has resulted in magnifying the use of assisted reproductive treatment (ART). Hence, genital microbiota and its impact on fertility has generated immense interest in recent years. In this systematic review, we searched the available evidence on the microbiota of the genital tract in women undergoing ART and studied the outcomes of IVF in different microbial compositions. Despite the inconsistency of the studies, it is evident that vaginal, cervical and endometrial microbiota might play a role in predicting ART outcomes. However, there is no clear evidence yet on whether the diversity, richness, quantity, or composition of species in the maternal genital tract significantly affects the outcomes in ARTs.

Dubinskaya, A., et al. (2023). "Is it time for doctors to Rx vibrators? A systematic review of pelvic floor outcomes." Sexual Medicine Reviews 11(1): 15-22.
	Introduction: Vibrators and similar devices are an underutilized treatment modality in pelvic and sexual medicine, likely because of the limited knowledge on the health benefits of their use. Objective(s): The aim of this study was to review available data regarding the effect of vibrator use on sexual function, pelvic floor function, and chronic unexplained vulvar pain. Method(s): We performed a systematic literature review of PubMed, Embase, and MEDLINE from inception to March 2021 per the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). The search was based on the following sex toy woman, pelvic vibrator, sexual stimulation vibrator, vaginal vibrator, vibrator pelvic floor, vibrator incontinence, and vulvar pain vibrator. An overall 586 articles were identified. Studies that met inclusion criteria were reviewed: original research, sample of women, vibrator use, and application to the pelvic/genital area. Exclusion criteria included case reports, unrelated content, vibrator not applied to the pelvic/genital area, male participants, or conditions of interest not addressed. A total of 17 original studies met the criteria and were reviewed in depth. Result(s): After review of the literature and identification of articles appropriate for the study, there were 8 studies surrounding sexual function, 8 on pelvic floor function (muscle strength/urinary incontinence), and 1 on vulvar pain. Among the identified studies, vibrators were considered an accepted modality to enhance a woman's sexual experience, improve pelvic floor muscle function, and facilitate treatment of vulvar pain. Conclusion(s): Vibrators are not well studied, and given the promising benefits demonstrated in the articles identified, future research efforts should be directed toward investigating their utility. Considering the potential pelvic health benefits of vibrators, their recommendation to women could be included in our pelvic floor disorder treatment armamentarium.Copyright © The Author(s) 2023.

Dubol, M., et al. (2020). "Neuroimaging premenstrual dysphoric disorder: A systematic and critical review." Frontiers in Neuroendocrinology 57: 100838.
	Endocrine organizational and activational influences on cognitive and affective circuits are likely critical to the development of premenstrual dysphoric disorder (PMDD), a sex-specific hormone-dependent mood disorder. An overview of the anatomical and functional neural characterization of this disorder is presented here by means of neuroimaging correlates, identified from eighteen publications (n = 361 subjects). While white matter integrity remains uninvestigated, greater cerebellar grey matter volume and metabolism were observed in patients with PMDD, along with altered serotonergic and GABAergic neurotransmission. Differential corticolimbic activation in response to emotional stimuli distinguishes the PMDD brain, namely enhanced amygdalar and diminished fronto-cortical function. Thus far, the emotional distress and dysregulation linked to PMDD seem to be defined by structural, chemical and functional brain signatures; however, their characterization remains sparsely studied and somewhat inconsistent. Clear and well-replicated neurobiological features of PMDD are needed to promote timely diagnoses and inform development of prevention and treatment strategies. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dubol, M., et al. (2021). "Neuroimaging the menstrual cycle: A multimodal systematic review." Frontiers in Neuroendocrinology 60.
	Increasing evidence indicates that ovarian hormones affect brain structure, chemistry and function of women in their reproductive age, potentially shaping their behavior and mental health. Throughout the reproductive years, estrogens and progesterone levels fluctuate across the menstrual cycle and can modulate neural circuits involved in affective and cognitive processes. Here, we review seventy-seven neuroimaging studies and provide a comprehensive and data-driven evaluation of the accumulating evidence on brain plasticity associated with endogenous ovarian hormone fluctuations in naturally cycling women (n = 1304). The results particularly suggest modulatory effects of ovarian hormones fluctuations on the reactivity and structure of cortico-limbic brain regions. These findings highlight the importance of performing multimodal neuroimaging studies on neural correlates of systematic ovarian hormone fluctuations in naturally cycling women based on careful menstrual cycle staging. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

DuBose, L. E., et al. (2022). "Role of BH4 Deficiency as a Mediator of Oxidative Stress-Related Endothelial Dysfunction in Menopausal Women." American journal of physiology. Heart and circulatory physiology 323(5): H975‐H982.
	Endothelial function (brachial artery flow‐mediated dilation [FMD]) is reduced in estrogen‐deficient postmenopausal women, mediated, in part, by reduced nitric oxide (NO) bioavailability, secondary to tetrahydrobiopterin (BH4) deficiency and oxidative stress. FMD is increased, but not fully restored, in postmenopausal women after acute intravenous vitamin C (VITC; superoxide scavenger) or oral BH4 supplementation. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite. To investigate mechanisms of endothelial dysfunction in women, we assessed the separate and combined effects of VITC and BH4 to determine whether coadministration of VITC + BH4 improves FMD in healthy postmenopausal women (n = 19, 58 ± 5 yr) to premenopausal (n = 14, 36 ± 9 yr) levels, with exploratory testing in perimenopausal women (n = 8, 51 ± 3 yr). FMD was measured during acute intravenous infusions of saline (control) and VITC (∼2‐3 g) ∼3 h after a single dose of oral BH4 (KUVAN, 10 mg/kg body wt) or placebo (randomized crossover, separated by ∼1 mo). Under the placebo condition, FMD was reduced in postmenopausal compared with premenopausal women during the saline infusion (5.6 ± 0.7 vs. 11.6 ± 0.9%, P < 0.001) and increased in postmenopausal women during VITC (+3.5 [1.4, 5.6]%, P = 0.001) and acute BH4 (+1.8 [0.37, 3.2]%, P = 0.01) alone. Coadministration of VITC + BH4 increased FMD in postmenopausal women (+3.0 [1.7, 4.3]%, P < 0.001), but FMD remained reduced compared with premenopausal women (P = 0.02). Exploratory analyses revealed that VITC + BH4 did not restore FMD in perimenopausal women to premenopausal levels (P = 0.045). Coadministration of VITC + BH4 does not restore FMD in menopausal women, suggesting that additional mechanisms may be involved.NEW & NOTEWORTHY Endothelial function is reduced across the menopausal stages related to increased oxidative stress associated with estrogen deficiency. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite; however, this remains untested in humans. We demonstrate that the coadministration of BH4 + VITC does not restore endothelial function in perimenopausal and postmenopausal women to the level of premenopausal women, suggesting that other mechanisms contribute.

Duenas-Gonzalez, A. and A. Gonzalez-Fierro (2019). "Pharmacodynamics of current and emerging treatments for cervical cancer." Expert Opinion on Drug Metabolism and Toxicology 15(8): 671-682.
	Introduction: Beyond early stages of cervical cancer (1A1, IA2, IB1, IIA1,), locally advanced disease (IB2, IIA2, IIA2, IIB, IIIA, IIIB, IIIC, IVA) and advanced (metastatic, recurrent or persistent disease) patients require drug therapy either as radiosensitizer, adjuvant or as palliative systemic chemotherapy. Areas covered: This review briefly discusses the achievements in treating cervical cancer. Expert opinion: Two studies are ongoing to optimize treatment after radical hysterectomy. These studies compare chemoradiation versus radiation in intermediate-risk patients or increasing treatment intensity (chemoradiation plus adjuvant chemotherapy versus chemoradiation) for high-risk and locally advanced cervical cancer. Concerning advanced disease, bevacizumab increased median survival for only 3.5 months when added to a cisplatin-doublet. Although this increase is slightly superior to the 2.9 months gained with cisplatin topotecan versus cisplatin, (0.6 months of difference), the doublet plus bevacizumab is considered the standard of care. Recently, pembrolizumab became an alternative for advanced disease that progresses to first-line treatment. Beyond that, the number of phase II and phase III trials in advanced disease is limited but on the increase. HPV E6/E7 oncoproteins are the Achilles Heel of cervical cancer, and there is cautious optimism that antagonists of these oncoproteins will be further developed.Copyright © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Duffy, J., et al. (2020). "A core outcome set for future endometriosis research: an international consensus development study." BJOG : an international journal of obstetrics and gynaecology 127(8): 967-974.
	Objective: To develop a core outcome set for endometriosis.; Design: Consensus development study.; Setting: International.; Population: One hundred and sixteen healthcare professionals, 31 researchers and 206 patient representatives.; Methods: Modified Delphi method and modified nominal group technique.; Results: The final core outcome set includes three core outcomes for trials evaluating potential treatments for pain and other symptoms associated with endometriosis: overall pain; improvement in the most troublesome symptom; and quality of life. In addition, eight core outcomes for trials evaluating potential treatments for infertility associated with endometriosis were identified: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss, including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; live birth; time to pregnancy leading to live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital abnormalities. Two core outcomes applicable to all trials were also identified: adverse events and patient satisfaction with treatment.; Conclusions: Using robust consensus science methods, healthcare professionals, researchers and women with endometriosis have developed a core outcome set to standardise outcome selection, collection and reporting across future randomised controlled trials and systematic reviews evaluating potential treatments for endometriosis. TWEETABLE ABSTRACT: @coreoutcomes for future #endometriosis research have been developed @jamesmnduffy. (© 2020 Royal College of Obstetricians and Gynaecologists.)

Duffy James, M. N., et al. (2019). "Tackling poorly selected, collected, and reported outcomes in obstetrics and gynecology research." American Journal of Obstetrics and Gynecology 220(1): 71.e71-71.e74.
	Clinical research should ultimately improve patient care. To enable this, randomized controlled trials must select, collect, and report outcomes that are both relevant to clinical practice and genuinely reflect the perspectives of key stakeholders including health care professionals, researchers, and patients. Unfortunately, many randomized controlled trials fall short of this requirement. Complex issues, including a failure to take into account the perspectives of key stakeholders when selecting outcomes, variations in outcome definitions and measurement instruments, and outcome reporting bias make research evidence difficult to interpret, undermining the translation of research into clinical practice. Problems with poor outcome selection, measurement, and reporting can be addressed by developing, disseminating, and implementing core outcome sets. A core outcome set represents a minimum data set of outcomes developed using robust consensus science methods engaging diverse stakeholders including health care professionals, researchers, and patients. Core outcomes should be routinely utilized by researchers, collected in a standardized manner, and reported consistently in the final publication. They are currently being developed across our specialty including infertility, endometriosis, and preeclampsia. Recognizing poorly selected, collected, and reported outcomes as serious hindrances to progress in our specialty, more than 80 journals including the Journal, have come together to support the Core Outcomes in Women's and Newborn Health (CROWN) initiative. The consortium supports researchers to develop, disseminate, and implement core outcome sets. Implementing core outcome sets could make a profound contribution to addressing poorly selected, collected, and reported outcomes. Implementation should ensure future randomized controlled trials hold the necessary reach and relevance to inform clinical practice, enhance patient care, and improve patient outcomes. (Copyright © 2018 Elsevier Inc. All rights reserved.)

Duffy, J. M. N., et al. (2020). "Top 10 priorities for future infertility research: an international consensus development study† ‡." Human reproduction (Oxford, England) 35(12): 2715-2724.
	Study Question: Can the priorities for future research in infertility be identified?; Summary Answer: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified.; What Is Known Already: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems.; Study Design, Size, Duration: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care.; Participants/materials, Setting, Methods: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance.; Main Results and the Role of Chance: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science.; Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions.; Wider Implications of the Findings: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda.; Study Funding/competing Interest(s): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Me icine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form.; Trial Registration Number: N/A. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Duffy, J. M. N., et al. (2021). "Top 10 priorities for future infertility research: an international consensus development study." Fertility and Sterility 115(1): 180-190.
	Study Question: Can the priorities for future research in infertility be identified?; Summary Answer: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified.; What Is Known Already: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems.; Study Design, Size, Duration: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care.; Participants/materials, Setting, Methods: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance.; Main Results and the Role of Chance: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science.; Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions.; Wider Implications of the Findings: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda.; Study Funding/ Competing Interest(s): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FI O Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form.; Trial Registration Number: Not applicable. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Duffy, J. M. N., et al. (2020). "Developing a core outcome set for future infertility research: an international consensus development study† ‡." Human reproduction (Oxford, England) 35(12): 2725-2734.
	Study Question: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed?; Summary Answer: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility.; What Is Known Already: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret.; Study Design, Size, Duration: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries).; Participants/materials, Setting, Methods: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods.; Main Results and the Role of Chance: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable.; Limitations, Reasons for Caution: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold.; Wider Implications of the Findings: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.; Study Funding/competing Interest(s): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form.; Trial Registration Number: Core Outcome Measures in Effectiveness Trials Initiative: 1023. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Duffy, J. M. N., et al. (2021). "Developing a core outcome set for future infertility research: an international consensus development study." Fertility and Sterility 115(1): 191-200.
	Study Question: Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed?; Summary Answer: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility.; What Is Known Already: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret.; Study Design, Size, Duration: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries).; Participants/materials, Setting, Methods: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods.; Main Results and the Role of Chance: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable.; Limitations, Reasons for Caution: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold.; Wider Implications of the Findings: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set.; Study Funding/competing Interest(s): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form.; Trial Registration Number: Core Outcome Measures in Effectiveness Trials Initiative: 1023. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Duffy, J. M. N., et al. (2020). "Standardizing definitions and reporting guidelines for the infertility core outcome set: An international consensus development study." Human Reproduction 35(12): 2735-2745.
	STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have comple ed the disclosure form.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

Dufour, S., et al. (2023). "Technical Update No. 433: eHealth Solutions for Urinary Incontinence Among Women." Journal of Obstetrics and Gynaecology Canada 45(2): 150-159.e151.
	Objective: The purpose of this technical update is to establish the state of the science regarding emerging and novel electronic health (eHealth) and mobile health (mHealth) solutions for urinary incontinence among women. Target population: Women over 18 years with urinary incontinence. Options: Websites and mobile health applications are useful in the conservative care of urinary incontinence. Relevant care providers should be familiar with such tools, particularly those that use motivational principles for behaviour change, which can be used as adjunct tools for urinary incontinence care. Telemedicine is an effect mode to provide services for the conservative care of urinary incontinence. Outcome(s): Use of eHealth and mHealth solutions has potentially significant health outcomes for patients, providers, and global health systems. Broader use of telemedicine, in and of itself, could improve care access and reduce costs incurred by patients and the health care system. Benefits, Harms, and Costs: Evidence for the efficacy of eHealth and mHealth technologies and applications for urinary incontinence ranges from weak to strong. However, the research landscape for many of these novel solutions is developing rapidly. Furthermore, these options have minimal or no harm and confer an established cost benefit and care access benefit. Evidence: The Cochrane Library, Medline, EMBASE, CENTRAL databases (from January 2014 to April 2019) were searched to find articles related to conservative care of urinary incontinence in women (over 18 years) and studies on eHealth and mHealth interventions for urinary incontinence. Articles were appraised, and the collective evidence was graded. Validation methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). Intended audience: Relevant primary care providers and medical specialists, including physicians, nurses, midwives, and pelvic health physiotherapists. SUMMARY STATEMENTS: 1. Electronic and mobile health interventions for urinary incontinence are growing, both in their availability in the health care market and in the science to support their use (moderate). 2. Electronic health interventions offered in conjunction with pelvic floor muscle training, either self-directed or directed by a health care provider (physiotherapist), may provide a marginal benefit in symptom improvement for stress urinary incontinence among women (low). 3. Application- and web-based programming for urinary incontinence should include traditional components of self-management programs, including motivational strategies to support behavioural interventions (high). 4. Bladder diaries are the most studied electronic health tool for overactive bladder and urge urinary incontinence. The acceptability and feasibility of these mobile health solutions has been established (low). 5. There is limited research on how electronic health interventions improve urge urinary incontinence and overactive bladder (low). 6. Telehealth can be an effective platform for patient education and counselling on conservative and surgical management of uncomplicated stress urinary incontinence (high). RECOMMENDATIONS: 1. Mobile health solutions, such as applications that incorporate evidence-based, motivational, behavioural intervention principles, should be recommended to women with stress urinary incontinence if tailored in-person care is not available or accessible (strong, high). 2. There is currently insufficient evidence to recommend the routine use of electronic health interventions that include a physical device to improve stress urinary incontinence symptoms (conditional, very low). 3. Electronic health interventions may be recommended to complement stress urinary incontinence treatment, but providers should familiarize themselves with the specific interventions recommended, since they va y significantly in terms of composition, cost, and benefit (conditional, very low). 4. Health care providers remain the key knowledge translators and advisors on overactive bladder and urge urinary incontinence; they should not assume that patients will get the information they need from a website (strong, moderate). 5. Health care providers may recommend web-based self-management programs that incorporate evidence-based motivational behavioural intervention principles if tailored in-person care is not available or accessible to patients (strong, low). 6. Application-based bladder diaries may be used as an alternative to traditional bladder diaries as a self-monitoring tool (conditional, low). 7. Follow-up visits for uncomplicated stress urinary incontinence may be considered in women who are comfortable with this platform (strong, low). 8. Although there is insufficient evidence to recommend virtual or telehealth consultation for routine pessary care instructions, these platforms can be considered on a case-by-case basis depending on the patient's comfort with pessary self-care (conditional, very low). 9. Surgical counselling for stress urinary incontinence via telehealth or virtual platforms may be considered for women who are comfortable with shared decision-making on these platforms (strong, moderate). 10. Post-operative virtual visits may be offered as an alternative to in-person visits after uncomplicated surgery for stress urinary incontinence (strong, moderate).Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Societe des obstetriciens et gynecologues du Canada

Dumbala, S., et al. (2020). "Effect of Yoga on Psychological Distress among Women Receiving Treatment for Infertility." International journal of yoga 13(2): 115-119.
	BACKGROUND: Infertility among women has been associated with significant psychological distress, anxiety, and depression. yoga therapy has been found to be useful in the management of anxiety, depression and psychological distress. AIM: To review studies on the effectiveness of yoga in reducing psychological distress and improving clinical outcomes among women receiving treatment for infertility. METHODOLOGY: PubMed, ScienceDirect, and Google Scholar databases were searched for studies using the following inclusion criteria: studies published in English, those published between 2000 and 2018, published in peer-reviewed journals, and those with Yoga as an intervention. Review articles, studies without any yoga interventions for infertility, and male infertility were excluded. The keywords included for the literature search were: Yoga, Mindfulness, Relaxation technique, Stress, Distress, Anxiety, Infertility, In Vitro Fertilization (IVF), and Assisted Reproductive Technology (ART). RESULTS: Three studies satisfied the selection criteria. Two studies involved Hatha yoga intervention and one study used structured yoga program. The variables assessed in these studies were: (1) anxiety, (2) depression, (3) emotional distress, and (4) fertility-related quality of life. All the studies reported an improvement in the anxiety scores after yoga intervention. CONCLUSION: Yoga therapy may be potentially useful in improving anxiety scores among women suffering from infertility. More studies are needed in this area to establish role of yoga as an adjuvant during the treatment of infertility.

Dumesic Daniel, A., et al. (2023). "Randomized clinical trial: effect of low-dose flutamide on abdominal adipogenic function in normal-weight women with polycystic ovary syndrome." Fertility and Sterility 119(1): 116-126.
	Objective: To examine whether low-dose flutamide administration to normal-weight women with polycystic ovary syndrome (PCOS) reduces abdominal fat deposition, attenuates accelerated lipid accumulation in newly formed adipocytes derived from subcutaneous (SC) abdominal adipose stem cells (ASCs), and/or alters glucose-lipid metabolism.; Design: A double-blind, placebo-controlled randomized clinical trial.; Setting: An academic medical center.; Patient(s): Twelve normal-weight women with PCOS and 12 age- and body mass index-matched controls.; Intervention(s): Women underwent circulating hormonal and metabolic determinations, intravenous glucose tolerance testing, total body dual-energy roentgenogram absorptiometry, and SC abdominal fat biopsy. Interventions were repeated in women with PCOS after 6-month administration of flutamide (125 mg orally daily) vs. placebo.; Main Outcome Measure(s): Clinical parameters and lipid accumulation in newly formed adipocytes derived from SC abdominal ASCs in vitro were compared between controls and the women with PCOS receiving flutamide vs. placebo.; Results: Serum luteinizing hormone and androgen levels as well as lipid accumulation in newly formed SC abdominal adipocytes were greater in the women with PCOS than controls. Flutamide vs. placebo reduced percent android fat, lowered serum log low-density lipoprotein and log non-high-density lipoprotein levels, and increased fasting circulating glucose levels. In all women with PCOS, changes in percent android fat positively correlated with serum log non-high-density lipoprotein and log low-density lipoprotein levels, with correlations influenced by serum free testosterone levels. Flutamide vs. placebo also attenuated lipid accumulation in newly-formed PCOS SC abdominal adipocytes in vitro relative to controls, which was unrelated to serum lipid levels.; Conclusion: Low-dose flutamide administration to normal-weight PCOS women reduces preferential abdominal fat deposition, attenuates accelerated lipid accumulation in newly-formed adipocytes derived from SC abdominal ASCs in vitro, and alters glucose-lipid homeostasis.; Clinical Trial Registration Number: NCT01889199 (URL, clinicaltrials.gov; date of registration, 6/28/2013; enrollment date of first subject, 6/28/2013). (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Duncan-Lothamer, C., et al. (2022). "The Use of Dye-Less Cystoscopy in Assessing Urinary-Tract Integrity During Hysterectomy." Journal of Gynecologic Surgery 38(5): 348-353.
	Objective: The goal of this research was to determine if dye can be omitted without affecting the accuracy of urinary-tract injury assessment during cystoscopy at the time of hysterectomy. Material(s) and Method(s): This prospective randomized study was performed at a gynecologic oncology service in a tertiary-care center from July 2018 to June 2019. All patients undergoing hysterectomy for either benign and malignant indications were included. The study focused on the routine cystoscopy given to each patient per protocol. Patients were randomized into 2 main groups: (1) dye versus (2) no-dye, and then into 4 subgroups based on the distending media that was used (water or saline). A linear, continuous visual scale was used to grade ureteral jet strength. The time to visualization of ureteral jets was documented. The primary outcome measure was the degree of agreement between 2 observers' ratings of ureteral jet strengths when urinary dye was used or when it was not used. Result(s): According to Cronbach's alpha, the correlation between 2 observers was 85.3% agreement for the strength of the right-side ureteral jets and 85.8% for the left side ureteral jets. The difference in jet strength between the dye and no-dye groups was statistically significant for evaluation of the right-side ureter but not clinically significant. No statistical significance for assessment of ureteral jet strength was noted between water and saline distension media nor was there a difference between the groups for time until first jet visualization. Conclusion(s): Cystoscopy can be performed without using dye for ureter and bladder assessment during gynecologic surgeries. (J GYNECOL SURG 38:348)Copyright © 2022, Mary Ann Liebert, Inc.

duPont Nefertiti, C., et al. (2022). "Prognostic significance of ethnicity and age in advanced stage epithelial ovarian cancer: An NRG oncology/gynecologic oncology group study." Gynecologic Oncology 164(2): 398-405.
	Background: Age and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy.; Methods: Women with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial. All women had surgical staging and received adjuvant chemotherapy with one of three regimens. Cox proportional hazards models were used to evaluate the relationship between OS with age and race/ethnicity among the study participants.; Results: One-thousand-eight-hundred-seventy-three women were enrolled in the study. There were 280 minority women and 328 women over the age of 70. Women age 70 and older had a 34% increase risk for death when compared to women under 60 (HR = 1.34; 95% CI 1.16-1.54). Non-Hispanic Black women had a 54% decreased risk of death with the addition of maintenance bevacizumab (HR = 0.46, 95% CI:0.26-0.83). Women of Asian descent had more hematologic grade 3 or greater adverse events and a 27% decrease risk of death when compared to non-Hispanic Whites (HR = 0.73; 95% CI: 0.59-0.90).; Conclusions: Non-Hispanic Black women showed a decreased risk of death with the addition of bevacizumab and patients of Asian ancestry had a lower death rate than all other minority groups, but despite these clinically meaningful improvements there was no statistically significant difference in OS among the groups. (Copyright © 2021. Published by Elsevier Inc.)

Dupuit, M., et al. (2020). "Effect of high intensity interval training on body composition in women before and after menopause: a meta-analysis." Experimental physiology 105(9): 1470-1490.
	New Findings: What is the topic of this review? A meta-analysis of the efficacy of high intensity interval training (HIIT) in reducing weight, total fat mass (FM) and (intra)-abdominal FM in normal-weight and overweight/obese women before and after menopause. What advances does it highlight? HIIT programmes in women significantly decrease body weight and total and abdominal FM. Their effects are more evident in pre- than in postmenopausal women. Cycling HIIT seems more effective than running, especially in postmenopausal women, and training interventions longer than 8 weeks comprising three sessions a week should be promoted.; Abstract: High-intensity interval training (HIIT) is a stimulating modality for reducing body weight and adipose tissue. The purpose of this meta-analysis was to assess the efficacy of HIIT in reducing weight, total fat mass (FM) and (intra)-abdominal FM in normal-weight and overweight/obese women before and after menopause. A structured electronic search was performed to find all publications relevant to our review. Stratified analyses were made of hormonal status (pre- vs. postmenopausal state), weight, HIIT modalities (cycling vs. running), programme duration (< or ≥8 weeks) and the methods used to measure body composition (dual-energy X-ray absorptiometry vs. computed tomography, Magnetic Resonance Imaging and others). A total of 38 studies involving 959 subjects were included. Our meta-analysis showed that overall HIIT programmes significantly decrease weight, total and abdominal FM in women. Both normal weight and overweight/obese women lost total FM after HIIT protocols whereas HIIT was only effective in decreasing abdominal FM in women with excess adiposity. When pre- and postmenopausal women were considered separately, the effect of HIIT on weight, total and abdominal FM were only significant before menopause. Cycling HIIT seemed more effective than running, especially in postmenopausal women, and training interventions longer than 8 weeks comprising three sessions were more efficient. HIIT is a successful strategy to lose weight and FM in normal weight and overweight/obese women. However, further studies are still needed to draw meaningful conclusions about the real effectiveness of HIIT protocols in postmenopausal women. (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Duralde Erin, R., et al. (2023). "Management of perimenopausal and menopausal symptoms." BMJ (Clinical research ed.) 382: e072612.
	Most women worldwide experience menopausal symptoms during the menopause transition or postmenopause. Vasomotor symptoms are most pronounced during the first four to seven years but can persist for more than a decade, and genitourinary symptoms tend to be progressive. Although the hallmark symptoms are hot flashes, night sweats, disrupted sleep, and genitourinary discomfort, other common symptoms and conditions are mood fluctuations, cognitive changes, low sexual desire, bone loss, increase in abdominal fat, and adverse changes in metabolic health. These symptoms and signs can occur in any combination or sequence, and the link to menopause may even be elusive. Estrogen based hormonal therapies are the most effective treatments for many of the symptoms and, in the absence of contraindications to treatment, have a generally favorable benefit:risk ratio for women below age 60 and within 10 years of the onset of menopause. Non-hormonal treatment options are also available. Although a symptom driven treatment approach with individualized decision making can improve health and quality of life for midlife women, menopausal symptoms remain substantially undertreated by healthcare providers.; Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Duran-Retamal, M., et al. (2020). "Live birth and miscarriage rate following intracytoplasmic morphologically selected sperm injection vs intracytoplasmic sperm injection: An updated systematic review and meta-analysis." Acta Obstetricia et Gynecologica Scandinavica 99(1): 24-33.
	Introduction: Intracytoplasmic morphologically selected sperm injection (IMSI) is one of the sperm selection techniques used for assisted reproduction which has been applied for a variety of indications including previously failed fertilization with intracytoplasmic sperm injection (ICSI). A Cochrane review 1 found no difference in outcomes between either modality of sperm selection. Since the Cochrane review was published there have been a further two randomized controlled trials comparing IMSI and ICSI. This systematic review and meta-analysis aims to compare IMSI with ICSI as insemination methods regarding live birth rate and miscarriage rate.; Material and Methods: Systematic review of randomized controlled trials, observational studies and similar reviews in electronic databases published before January 2018.; Results: We found nine randomized controlled trials, evaluating 1610 cycles of in vitro fertilization and 15 observational studies evaluating 1243 cycles of in vitro fertilization. Meta-analysis of the included randomized controlled trials showed no difference in the live birth rate or miscarriage rate between the ICSI and IMSI groups. Meta-analysis of five observational studies showed a significantly higher number of live births in the IMSI group than ICSI group (live birth rate odds ratio 1.47, 95% confidence interval 1.16-4.07), with a moderate degree of heterogeneity (I 2 = 41%). Additionally, from six observational studies, a significantly lower miscarriage rate was observed in the IMSI group than in the ICSI group (odds ratio 0.51, 95% confidence interval 0.37-0.70, I 2 = 0%).; Conclusions: Meta-analysis of randomized studies comparing IMSI to ICSI has not shown any difference in live birth rate and miscarriage rate. Meta-analysis of observational studies, which must be interpreted with caution, revealed an increased live birth rate and decreased miscarriage rate with IMSI vs ICSI. (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Durmaz, A. and G. Kakaşçı Ç (2022). "THE EFFECTS OF WOMAN-CENTERED CARE ON VITAL SIGNS, ANXIETY AND COMFORT LEVELS: a RANDOMIZED CONTROLLED TRIAL." Karya journal of health science 3(2): 133‐139.
	
Dursun, M., et al. (2024). "The effect of transobturator tape surgery on female sexual function: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics.
	Purpose: We aimed to review the literature regarding the effects of trans obturator tape surgery (TOT) on sexual functions in women with stress urinary incontinence (SUI) to reveal compact data and to reach more consistent and reliable results. Method(s): PRISMA statement was used in the current review. The databases of PubMed (Medline), Science Direct, and Cochrane Central Register of Controlled Trials were detected independently. We evaluated the studies comparing the preoperative and postoperative sexuality parameters related to the TOT procedure in females. Studies presenting the mean and standard deviation(SD) of global and sub-item Female Sexual Function Index(FSFI) were included in the current study. Result(s): We identified 783 studies in full publications or abstract forms using the methodology above and the search terms. Finally, eight studies were included in the meta-analysis. The pooled analysis of the mean difference demonstrated that the total sexual function scores of the patients improved after TOT surgery. Conclusion(s): The data collected from the current meta-analysis suggest that TOT surgery improves female sexual function.Copyright © 2024, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Duska Linda, R., et al. (2023). "Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer." JCO precision oncology 7: e2300235.
	Purpose: The Bromodomain and Extra-Terminal (BET) domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with ARID1A loss. PLX2853 is an orally active, small-molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all four BET family members.; Methods: We conducted a multicenter and open-label study with two parallel arms: a phase IIa study of PLX2853 monotherapy in patients with advanced gynecologic malignancies with an ARID1A mutation and a phase Ib/IIa combination study of PLX2853 plus carboplatin in women with platinum-resistant OC. The primary objectives were safety and tolerability for phase Ib and efficacy for both phase IIa portions. Thirty-four of 37 enrolled patients completed at least one post-baseline response assessment.; Results: Of the 14 evaluable patients on the monotherapy arm, 1 (7.1%) achieved a best overall response of partial response (PR), 5 (35.7%) had stable disease (SD), and 8 (57.1%) had progressive disease (PD). Of the 20 evaluable patients on the combination arm, 1 (5.0%) had PR, 9 (45.0%) had SD, and 10 (50%) had PD.; Conclusion: This study confirmed the safety profile of PLX2853 and demonstrated the feasibility of combination with carboplatin. Although these results did not meet the prespecified response criteria, evidence of clinical activity highlights the rationale for further exploration of BET inhibitors in patients with ARID1A -mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway.

Duska, L. R., et al. (2021). "A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response." Clinical Cancer Research 27(10): 2734‐2741.
	Purpose: This surgical window of opportunity (window) study assessed the short‐term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma. Patients and Methods: This multisite, randomized, open‐label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21–24. Pretreatment and posttreatment tissue was assessed for PR H‐scores, Ki‐67 levels, and histologic response. Results: Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H‐scores were significantly lower than pretreatment H‐scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, P ¼ 0.87). Decreased Ki‐67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (P ¼ 0.13). Median PR H‐score decreases were larger when Ki‐67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki‐67 nuclear staining, consistent with reduced cellular proliferation (P < 0.008). Conclusions: This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki‐67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short‐term study, lessons learned can inform future window and treatment trials.

Duska, L. R., et al. (2021). "A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer." Gynecologic Oncology 160(3): 688-695.
	BACKGROUND: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC). METHODS: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. RESULTS: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed >1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). CONCLUSIONS: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words.

Dutra, L., et al. (2021). "Transcranial direct current electrical stimulation for the treatment of interstitial cystitis: a study protocol." European Journal of Obstetrics, Gynecology, and Reproductive Biology 262: 198‐202.
	Background: Interstitial cystitis or painful bladder syndrome is a chronic disorder that presents an unknown etiology, with no generally accepted treatment. Although there is no gold standard treatment, transcranial direct current stimulation (tDCS) has shown efficacy in several chronic pain syndromes with decrease in pain, and improved functionality and mood. tDCS could be a safe, ease to use, and low‐cost complementary intervention for patients with interstitial cystitis. Aim: This study will investigate the effects of a tDCS protocol on pain, functionality, and mood in patients with interstitial cystitis. Methods: A randomized controlled clinical trial with two arms. Women will be randomized into two groups: active or sham. Anodal tDCS over the primary motor cortex will be performed for 5 consecutive days with an intensity of 2 mA for 20 min. Participants will be evaluated five times: 1 week before intervention; on the 5th day of tDCS; and 1, 6, and 12 months after the last day of tDCS. The outcomes will be assessed using the numeric rating scale, McGill pain questionnaire, positive and negative affect scale, international consultation on incontinence questionnaire for female lower urinary tract symptoms, Hamilton anxiety scale, six‐minute walk test, patient global impression of change, and voiding diary. Discussion: Only the active group will be expected to show decreased pain. The results of this trial will be the first step in the use of neuromodulation in interstitial cystitis and will provide additional data to support new studies with tDCS.

Dutra, P., et al. (2021). "Comparison of topical fractional CO2 laser and vaginal estrogen for the treatment of genitourinary syndrome in postmenopausal women: a randomized controlled trial." Menopause (New York, N.Y.) 28(7): 756‐763.
	OBJECTIVE: To compare the efficacy of fractional CO2 laser therapy with topical estrogen therapy for the treatment of postmenopausal genitourinary syndrome of menopause. METHODS: We conducted a randomized controlled clinical trial involving 25 postmenopausal women. Participants were aged between 50 and 65 years with at least 1 year of amenorrhea and follicle‐stimulating hormone levels of >40 IU/L. The women were randomized into two groups: the laser therapy group (n = 13) and the vaginal topical estrogen therapy group (n = 12). Changes in the vaginal epithelium thickness, Frost index, and cell maturation were analyzed in both the groups. The female sexual quotient of each woman was also evaluated. Subjective evaluation was performed through a physical examination. RESULTS: Histological analysis showed a significant increase in the vaginal epithelium thickness at the end of treatment in females in both the laser therapy (P < 0.001) and topical estrogen therapy (P = 0.001) groups. The topical estrogen therapy group tended to present a higher maturation index at the end of treatment when compared with that of the other group. Sexual function increased significantly over time in both the topical estrogen therapy (P < 0.001) and laser therapy (P < 0.001) groups. Subjective evaluation through physical examination showed a significant improvement in atrophy in both the groups. CONCLUSION: Despite the nonequivalence with topical estrogen therapy, our data suggest that laser therapy is an effective method for the treatment of vulvovaginal atrophy.

Dutta, R., et al. (2022). "Safety and economics of an enhanced recovery after surgery protocol in pelvic reconstructive surgery." International Urogynecology Journal 33(7): 1875-1880.
	Introduction and Hypothesis: We hypothesized that an enhanced recovery after surgery (ERAS) protocol for patients undergoing female pelvic reconstructive surgery would conserve hospital resources without compromising patient safety.; Methods: In June 2020, an ERAS protocol designed to promote same-day discharge was initiated that included pre-operative hydration, a urinary anesthetic, non-narcotic analgesia, perineal ice, a bowel regimen, enrollment of the family to assist with care, and communication regarding planned same-day discharge. We compared demographic, operative, hospital stay, complications, and cost data in patients undergoing pelvic organ prolapse or incontinence surgery over 4 sequential months pre (PRE; N = 82) and post (POST; N = 91) ERAS implementation using univariate statistics.; Results: There were no differences in demographics, operative details, or complications (p > 0.05). There were no significant differences in overall revenues or expenses (p > 0.05), but bed unit cost was significantly lower in the POST group ($210 vs $533, p < 0.0001). There was a trend toward an increased operating margin in POST patients ($4,554 vs $2,151, p = 0.1163). Significantly more POST surgeries were performed in an ambulatory setting (73.6% vs 48.8%, p = 0.0008) and resulted in same-day discharge (80.2% vs 50.0%, p = 0.0003). There were no differences in the rates of emergency room or unexpected clinic visits (p > 0.05). Prescribed post-operative opiate dose was significantly reduced in POST patients (p < 0.0001).; Conclusions: In patients undergoing female pelvic reconstructive surgery, an ERAS protocol facilitated transfer of procedures to an ambulatory surgical site and permitted same-day discharge without increasing complications, clinic visits, or emergency room visits. It also reduced bed unit cost and may improve operating margins. (© 2021. The International Urogynecological Association.)

Dweck, A., et al. (2024). "Efficacy of a Nonhormonal Neurokinin B Inhibiting Supplement for Reducing Vasomotor Symptoms." Journal of Neurosurgical Anesthesiology 36(1): 1302-1303.
	Objective: The primary objective was to evaluate the effects of a nonhormonal, botanical blend (VMS-BH02; ThermellaTM), on hot flashes and night sweats in women who experience menopausal vasomotor symptoms (VMS). Preclinical studies showed that the combination of these ingredients synergistically inhibited the neurokinin B pathway and did not raise estrogen levels nor induce cell proliferation in MCF-7 cells. This was the first clinical study conducted to evaluate clinical benefits. Design(s): This is an ongoing open-label study in women 45-65 years of age. Thirty peri- and post-menopausal women were recruited if they reported a daily average of 5 or more VMS, regardless of severity. Participants were instructed to consume 2 capsules of the supplement daily. To date, participants have completed 8 weeks. The primary endpoint was the percent change in total VMS, collected using daily diaries. Secondary endpoints were assessed using various validated monthly questionnaires including the Menopause Specific Quality of Life (MENQOL), the Hot Flash Related Daily Interference Scale (HFRDIS), the Greene Climacteric Scale (GCS), and the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS). Participants completed all questionnaires at Baseline, and weeks 2, 4, and 8, with the exception of the MENQOL, which was not administered at week 2. Result(s): Thirty women completed 8 weeks (55.5 +/-3.7 yrs) of supplementation. There was a significant decrease in self-reported total VMS occurrences (all severities) noted across the time points (Baseline: 10.7 +/-6.0; Week 4: 6.2 +/-4.2; Week 8: 5.1 +/-4.4; p < 0.01). Combined, moderate and severe hot flashes were significantly decreased at all weeks when compared to baseline (Baseline: 5.1 +/-2.6; Week 4: 2.9 +/-2.6; Week 8: 2.5 +/-2.9; p < 0.01). Night sweats significantly decreased from baseline at weeks 4 and 8 (Baseline: 2.9 +/-2.1; Week 4: 1.5 +/-1.2, p = 0.002; Week 8: 1.4 +/-1.3, p < 0.01). Significant improvements were also noted in the MENQOL total sum at weeks 4 and 8 compared to baseline (Baseline: 3.8 +/-1.2; Week 4: 3.0 +/-1.1; Week 8: 2.7 +/-1.4; p < 0.01), the HFRDIS total sum at all timepoints compared to baseline (Baseline: 42.7 +/-18.2; Week 2: 31.03 +/-18.3; Week 4: 26.1 +/-20.4; Week 8: 18.4 +/-18.4; p < 0.001), and the GCS total sum at weeks 2, 4, and 8 compared to baseline (Baseline: 20.3 +/-8.6; Week 2: 16.3 +/-8.3, p < 0.001; Week 4: 14.1 +/-8.5, p = 0.001; Week 8: 12.5 +/-10.3, p < 0.001). There were also significant improvements in PROMIS total score at weeks 2, 4, and 8 compared to baseline (Baseline: 30.3 +/-7.0; Week 2: 26.4 +/-8.3; Week 4: 25.5 +/-8.1; Week 8: 23.4 +/-8.3; p < 0.01). Conclusion(s): The eight-week daily supplementation with ThermellaTM, which has a high affinity for inhibition of the NK3 receptor, resulted in significant and consistent reductions in vasomotor symptoms, including hot flashes and night sweats. These improvements were observed as early as two weeks into the study and continued throughout the investigation period. Notably, the frequency and severity of these symptoms decreased over time. Supplementation also showed positive effects on menopause-specific quality of life related outcomes and sleep disturbances. Overall, these findings underscore the promising clinical efficacy of this novel botanical blend in effectively managing vasomotor symptoms experienced by women throughout their menopausal transition.

Dwyer, L., et al. (2022). "Theoretical and practical development of the TOPSY self-management intervention for women who use a vaginal pessary for pelvic organ prolapse." Trials 23(1): 742.
	Background: Pelvic organ prolapse (POP) is a common condition in women, where the downward descent of pelvic organs into the vagina causes symptoms which impacts quality of life. Vaginal pessaries offer an effective alternative to surgery for the management of POP. However, the need for regular follow-up can be burdensome for women and requires significant healthcare resources. The TOPSY study is a randomised controlled trial which aims to determine the clinical and cost-effectiveness of self-management of vaginal pessaries. This paper describes the theoretical and practical development of the self-management intervention.; Methods: The intervention was developed using the MRC complex intervention framework, normalisation process theory (NPT) and self-management theory. The intervention aims to boost perceived self-efficacy in accordance with Bandura's social cognitive theory and is guided by the tasks and skills Lorig and Hollman describe as necessary to self-manage a health condition.; Results: The TOPSY intervention was designed to support women to undertake the medical management, role management and emotional management of their pessary. The six self-management skills described by Lorig and Hollman: problem-solving, decision-making, resource utilisation, formation of a patient-provider partnership role, action planning and self-tailoring, are discussed in detail, including how women were supported to achieve each task within the context of pessary self-management. The TOPSY intervention includes a self-management support session with a pessary practitioner trained in intervention delivery, a follow-up phone call 2 weeks later and ongoing telephone or face-to-face support as required by the woman initiated by contacting a member of the research team.; Conclusions: The TOPSY study intervention was developed utilising the findings from a prior service development project, intervention development and self-efficacy theory, relevant literature, clinician experience and feedback from pessary using women and members of the public. In 2022, the findings of the TOPSY study will provide further evidence to inform this important aspect of pessary management.; Trial Registration: ISRCTN Registry ISRCTN62510577 . Registered on June 10, 2017. (© 2022. The Author(s).)

Dybeck, M.-M., et al. (2022). "Can supervised group-based multimodal exercise improve health-related quality of life in women with ovarian cancer undergoing chemotherapy?" European journal of cancer care 31(4): e13607.
	
Eberle, A., et al. (2024). "Medical Management of Ovarian Endometriomas: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 143(1): 53-66.
	OBJECTIVE:To estimate the effect of medical management on the size of ovarian endometriomas.DATA SOURCE:Online databases were searched from inception to October 2022, including Ovid MEDLINE, Ovid EMBASE, PubMed, EBM Reviews - Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Web of Science.METHODS OF STUDY SELECTION:Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we included all English-language, full-text articles that reported on change in endometrioma size (either diameter or volume) after medical interventions. Studies evaluating surgical interventions or postoperative recurrence were excluded. All screening and data extraction were performed independently by two authors. Risk of bias assessment was performed with either the Cochrane Risk of Bias Tool for randomized controlled trials or a modified Newcastle-Ottawa Scale for observational studies.TABULATION, INTEGRATION, AND RESULTS:After removal of duplicates, 9,332 studies were screened, with 33 full-text articles deemed eligible for inclusion. In the meta-analysis, dienogest showed significant reduction in cyst diameter (reduction 1.32 cm, 95% CI, 0.91-1.73, eight studies, n=418 cysts) and volume (mean difference of log-transformed volume 1.35, 95% CI, 0.87-1.83, seven studies, n=282 cysts). Similarly, significant reductions were seen with the oral contraceptive pill (OCP) (1.06 cm, 95% CI, 0.59-1.53, nine studies, n=455), gonadotropin-releasing hormone (GnRH) agonists (1.17 cm, 95% CI, 0.42-1.92, four studies, n=128 cysts), norethindrone acetate (0.6 cm, 95% CI, 0.27-0.94, two studies, n=88 cysts), and danazol (1.95 cm, 95% CI, 1.18-2.73, two studies, n=34 cysts). Norethindrone acetate with aromatase inhibitor was also effective in reducing endometrioma volume (mean difference of log-transformed volume 1.47, 95% CI, 0.16-2.78, two studies, n=34 cysts). CONCLUSION(S):Medical management with dienogest, OCPs, GnRH agonists, norethindrone acetate, norethindrone acetate with aromatase inhibitor, or danazol can reduce the size of ovarian endometriomas.SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD 42022363319.Copyright © 2024 Lippincott Williams and Wilkins. All rights reserved.

Ebner, F., et al. (2019). "Results of an internal audit on the survival of patients with uterine sarcoma." Journal of the Turkish German Gynecological Association 20(1): 15-22.
	Objective: In the last 5 years there has been much discussion about the surgical procedure for uterine fibroids, and essentially, also uterine sarcoma. Still there exists no reliable presurgical diagnostic tool to differentiate between benign fibroids and uterine sarcomas. The aim of this study was to confirm the suspected association between intraoperative spread of tumor by morcellation and impaired outcomes in patients with sarcoma.; Material and Methods: After the local ethics commission positively reviewed the study protocol, the oncologic database of our university hospital was retrospectively reviewed for patients with uterine sarcomas over a time period of 13 years (2002-2015). Data was extracted from the medical files and survival information was collected by contacting the patient’s general practitioners if last follow-up-status was older than 6 months. For the analysis, patients were split into two groups with either intrasurgical morcellation (M+) or no morcellation (M-) regarding information provided by the surgical report.; Results: Data on 57 patients with uterine sarcoma were available for further analysis. The median age and body mass index of the patients was 63 years and 27 kg/m², respectively. The sarcoma subtypes were 25 leiomyosarcoma, 19 carcinosarcoma, 9 endometrioid stroma sarcoma, 3 adenosarcoma, and one case without further differentiation. In the majority, no morcellation was performed (M- group, n=44) and 51 patients received open surgery (3 laparoscopic, 1 vaginal, and 2 incomplete surgeries). The median time of follow-up was 31 months. The disease-free survival was 50.5 months and the Cox regression analysis showed a hazard ratio of 3.06 [no significant difference between the two subgroups (p=0.079; 95% confidence interval (CI): 0.9-10.6)]. The overall survival was found as 62.2 months and the Cox regression analysis showed a hazard ratio of 3.216 with a statistically significant difference between the two subgroups (p=0.013; 95% CI: 1.3-8.1).; Conclusion: Despite the efforts to find a pre-surgical diagnostic tool, the clinical situation remains unsatisfactory. Overall sarcoma prevalence is low during the last 13 years at our university center, but morcellation occurred in a relevant portion of patients (13 of 57). If sarcoma is suspected or diagnosed then en-bloc resection of the uterus can prolong survival. Thus, morcellation of the uterus and not the surgical technique (en-bloc resection) is the prognostic factor and should be avoided in any suspicious case.

Ebrahimi, A., et al. (2020). "Investigation of the role of herbal medicine, acupressure, and acupuncture in the menopausal symptoms: An evidence-based systematic review study." Journal of family medicine and primary care 9(6): 2638-2649.
	Background: Menopause is an important physiological phenomenon in women's lives. Women's concern about taking the hormone treatment to ease menopausal symptoms is increasing. Over the past decade, the use of complementary and alternative medicine for the treatment of menopausal problems instead of hormone therapy has increased.; Objective: This study aimed to investigate the role of herbal medicine, acupressure, and acupuncture in the menopausal symptoms.; Methods: Data source: related articles were searched from internal scientific databases and external databases of "Web of Scopus, Cochrane, PubMed, Science Direct, Ovid, and Google scholar."; Study Eligibility Criteria: The keywords such as menopause, menopausal symptoms, complementary menopausal medicine, acupuncture in menopause, herbal medicine in menopause, and acupuncture in menopause were searched in the studies from 1987 to 2019. Exclusion criteria were inadequate information in the study, lack of access to full-text articles, animal studies, and reports. At the end of the search, 145 articles out of a total of 400 articles were reviewed.; Results: In various studies, different herbs such as licorice, valerian, soy, sage, ginseng, etc., were used to improve menopausal symptoms. In addition, acupuncture and acupressure were used to reduce menopausal symptoms.; Conclusion: The efficacy and use of complementary and alternative medicine, along with other classical medicine care, can be a new model for improving menopausal symptoms in women. It is recommended that further clinical and review studies be conducted to develop complementary and alternative medicine.; Competing Interests: There are no conflicts of interest. (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

Eccles, H. and V. Sharma (2023). "The association between premenstrual dysphoric disorder and depression: A systematic review." Journal of Affective Disorders Reports 12: 100504.
	Background: Due to the high comorbidity of premenstrual dysphoric disorder (PMDD) with other psychiatric conditions, it is important to understand the relationship between PMDD and major depression. In this study we aim to review studies that investigated the prevalence of PMDD and in those with major depression and vice versa. Method(s): A systematic review was completed December 2021 using PubMed, PsychINFO, CINAHL and EMBASE. The inclusion criteria used included: (1) original research studies, (2) a diagnosis of current or past history of depression, (3) a diagnosis of late luteal phase disorder (LLPD) as per DSM-III-R or PMDD as defined in DSM-IV or DSM-5, and (4) published in English. The authors screened the titles and abstracts of papers that were original research with participants who had a history of depression and a diagnosis of PMDD or late luteal phase disorder. The reference lists of review papers were searched for other relevant literature. Result(s): After 90 articles were screened for relevance and inclusion criteria, 10 articles were included in the study. They were published from 2001 to 2018 and varied across demographic areas. All but one study found a positive association between PMDD and history or current depression. Many studies found that a history of depression (no current depression) was associated with PMDD. Limitation(s): The way the studies diagnosed PMDD and depression was heterogeneous. More than half the studies did not use daily prospective ratings, which is a necessary step for a final confirmed diagnosis of PMDD. Therefore, it is possible that at least some of these participants did not have PMDD. Conclusion(s): PMDD is a prevalent disorder that affects women across the world. People with PMDD should be monitored for future development of depression and vice versa. Treatment of depression should consider this association. More studies are needed to understand the mechanisms responsible for the association.Copyright © 2023 The Author(s)

Economics Izmir University, o. (2023). 360 Degree Expanded Diaphragm Exercises in Women With Stress Urinary Incontinence.
	This study was planned to examine and compare the effects of standard diaphragm exercises with Pelvic floor muscle exercises (PFME) and 360-degree expanded diaphragm exercises with PFME on urinary symptoms, PFM functions and quality of life in women with stress urinary incontinence. Priary measure: Change of Pelvic floor muscle contraction during Valsalva; 9 secondary measures: Conditions: Stress Urinary Incontinence Diaphragmatic Breathing Pelvic Floor Muscle Exercise Intra-abdominal Pressure

Edey Katharine, A., et al. (2019). "Interventions for the treatment of Paget's disease of the vulva." The Cochrane Database of Systematic Reviews 6: CD009245.
	Background: This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most common site of involvement is the vulva. It is seen mainly in postmenopausal white women. Paget's disease of the vulva often spreads in an occult fashion, with margins extending beyond the apparent edges of the lesion. There is a range of interventions from surgical to non-invasive techniques or treatments. The challenges of interventions are to remove or treat disease that may not be visible, without overtreatment and with minimisation of morbidity from radical surgery. There is little consensus regarding treatment. Surgery, by default, is the most common treatment, but it is challenging to excise the disease adequately, and recurrence is common, leading to repeated operations, and destruction of anatomy. Alternative treatments of photodynamic therapy, laser therapy, radiotherapy, topical treatments or even chemotherapy have been mooted, and it is important to evaluate the available evidence. It is essential to assess whether newer cell-specific treatments, such as photodynamic therapy and imiquimod, can reduce the need for radical surgery.; Objectives: To evaluate the benefits and harms of different treatment modalities for the management of Paget's disease of the vulva.; Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid) up to 8 May 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles.; Selection Criteria: We searched for randomised controlled trials (RCTs) and well-designed non-randomised studies that compared different interventions in women with Paget's disease of the vulva, DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, analysed no data.; Main Results: The search for the original version of the review identified 635 unique references. We found 31 references (which reported on 30 studies) in full text after inspection of titles and abstracts, but we excluded them all as they did not meet the inclusion criteria. However, we have included a comprehensive narrative account of studies where we identified an analysis of more than 10 women, as this forms the only evidence base in this rare disease. Surgery continues to be the mainstay of treatment in the current literature, with other treatments limited to case reports or treatment of inoperable or recurrent disease.This update between September 2013 and May 2018 identified 35 new studies. None of these met the inclusion criteria. There was only one prospective study of 5% imiquimod in recurrent Paget's disease of the vulva, which although of good quality only included eight women.; Authors' Conclusions: Since the last version of the review was published there are many more cases in the literature reporting a clinical response to 5% imiquimod cream. There is one prospective study of eight women treated with 5% imiquimod for recurrent Paget's disease of the vulva, and one prospective trial of 20 women was due to be reported. This increasing evidence for the safety and efficacy of 5% imiquimod will be helpful for women and clinicians alike. Ideally, a multicentre RCT of reasonable size is needed, but ongoing publications of high-quality non-randomised prospective studies will enhance the current available literature.

Edinoff, A. N., et al. (2021). "Brexanolone, a GABAA Modulator, in the Treatment of Postpartum Depression in Adults: A Comprehensive Review." Frontiers in Psychiatry 12: 699740.
	Postpartum depression (PPD) is one of the three major categories on the spectrum of postpartum psychiatric syndromes. Postpartum psychiatric syndromes are classified as either postpartum blues, postpartum depression, or postpartum psychosis. Postpartum depression is important to recognize clinically because of the effect it can have on the mother-child bond. The neurosteroid allopregnanolone, a progesterone derivative, is important for its role in positively modulating GABAA receptors. GABA-mediated signaling has been previously implicated in major depressive disorder. Allopregnanolone-mediated signaling has been identified as an important therapeutic target. Treatment with an allopregnanolone-analog, brexanolone, has been shown to improve depression scores in trials for the treatment of PPD. Brexanolone is a positive allosteric modulator of GABAA and is the first drug approved by the FDA to treat postpartum depression. Brexanolone enhances the inhibitory effects of GABAA, restores dysfunctional GABAA transmembrane channels, and mimics a naturally produced progesterone metabolite that fluctuates during pregnancy and postpartum. One open-label study and two phase two studies have some significant reduction in HAM-D scores after treatment and that the effect was still there 30 days post-treatment. Per the data reported, intravenous infusion of brexanolone could be efficacious and safe for the treatment of women suffering from postpartum depression.© Copyright © 2021 Edinoff, Odisho, Lewis, Kaskas, Hunt, Cornett, Kaye, Kaye, Morgan, Barrilleaux, Lewis, Viswanath and Urits.

Edmed Shannon, L., et al. (2022). "Sleep and health-related quality of life in women following a cancer diagnosis: results from the Women's Wellness after Cancer Program in Australia." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30(12): 10243-10253.
	Purpose: Sleep disturbance after cancer treatment could compromise recovery. This paper examined the associations between post-treatment sleep problems and health-related quality of life (HRQoL), and the effectiveness of an e-enabled lifestyle intervention on sleep outcomes.; Methods: The Women's Wellness after Cancer Program (WWACP) was examined in a single blinded, multi-centre randomised controlled trial. Data were collected from 351 women (M age = 53.2, SD = 8.8; intervention n = 175, control group n = 176) who had completed surgery, chemotherapy and/or radiotherapy for breast, gynaecological or blood cancers within the previous 24 months. Participants completed the Pittsburgh Sleep Quality Index (PSQI) at baseline (prior to intervention randomisation), and at 12 and 24 weeks later. Sociodemographic information, menopausal symptoms (Greene Climacteric Scale) and HRQoL (36-Item Short Form Health Survey; SF-36) were also collected. Linear panel regression was used to examine the association between sleep variables and SF36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. A difference-in-difference regression model approach was used to examine the intervention effect on the sleep outcomes.; Results: After adjustment for potential confounders, the sleep variables (except sleep duration) significantly predicted physical, but not mental, HRQoL. There was no statistically significant effect of the intervention on sleep outcomes at 12 or 24 weeks.; Conclusion: Women who have completed treatment for cancer experience sleep problems that are associated with decreased physical HRQoL. Improving sleep through targeted interventions should improve their physical HRQoL. Improved targeting of the sleep components of the WWACP should be explored. (© 2022. The Author(s).)

Edmonds, K., et al. (2023). "Apical support after laparoscopic hysterectomy for benign conditions: a randomized controlled trial comparing vaginal cuff closure techniques." American Journal of Obstetrics and Gynecology 228(3 Supplement): S821.
	Objectives: As the approximately 600,000 women that undergo minimally invasive hysterectomy per year age, they are at increased risk for pelvic organ prolapse. The route of vaginal cuff closure after total laparoscopic hysterectomy has not been standardized and can be performed laparoscopically or vaginally. This study was designed to compare pelvic floor support between these closure techniques after laparoscopic hysterectomy. Material(s) and Method(s): This randomized controlled trial included adult female patients scheduled to undergo a total laparoscopic hysterectomy for benign indication. Exclusion criteria included a planned concurrent prolapse procedure, malignancy, and a pelvic organ prolapse quantitation system (POPQ) C Point greater than -4. Preoperative (preop) POPQ exams were performed by blinded Urogynecologists to assess pelvic support within 1 month of surgery. Subjects were randomized to vaginal or laparoscopic cuff closure on the day of surgery. Vaginal closure was performed vertically with absorbable suture and laparoscopic closure was performed horizontally with delayed-absorbable suture. POPQ exams were then repeated by blinded Urogynecologists at 6-8 weeks and 1 year postoperatively (postop). The study was powered to detect a 1.75cm difference, with an estimated effect size of 0.97. Alpha was set at 0.025 to correct an alpha of 0.05 for two primary study timepoints. Attrition was set at 30% to account for patient dropout before the last measurement point at 1 year. Power was set at 0.8. These assumptions resulted in a required sample size of up to 31 patients per group, or 62 patients in total. Result(s): 57 subjects were enrolled in the study; 44 subjects completed 6-8 week follow-up, and 33 subjects were evaluated at 1 year. Subject enrollment and retention were impacted by the COVID-19 Pandemic resulting in a small sample size. Baseline demographics were similar between groups except for a significant difference between surgeon training status with laparoscopic closures performed mostly by fellows (82.6%) and vaginal closures performed mostly by residents (95.2%, p<0.001). The primary outcome of the mean difference of Point C (preop - postop value) between laparoscopic and vaginal closure was 0.98 cm and 1.24 cm, respectively at 6-8 weeks postop (p = 0.55), and 1.22 cm and 1.63 cm, respectively at 1 year postop (p = 0.48, Figure 1). These positive mean differences indicate increased apical support for both study groups and timepoints. Mean differences for all other points of the POPQ (Table 1) and postop complication rates were non-significant between groups at all timepoints. Conclusion(s): There is no significant difference in post-hysterectomy apical support after total laparoscopic hysterectomy between laparoscopic and vaginal cuff closure techniques at 6-8 weeks and 1 year postop. [Formula presented] [Formula presented]Copyright © 2022

Education Poznan University of, P. (2021). Effect of Time-restricted Eating on Cognitive Function and Other Biopsychosocial Factors in Menopausal Women Undertaking a 12-week Exercise Programme.
	No Results Available Behavioral: Exercise and Time-Restricted Eating|Behavioral: Exercise only Brain-derived neurotrophic factor|Glial cell derived neurotrophic factor|Insulin|Glucose|LDL-cholesterol|Muscle mass|Fat mass|Stroop test|N-back test|Electroencephalography|One-repetition maximum test|Ruffier test|Menopause Rating Scale|The Menopause-Specific Quality of Life Questionnaire Female Not Applicable 80 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Prevention BJozwiak_PhD July 1, 2023

Education Poznan University of, P., et al. (2023). Functional Links Between the Temporomandibular Joint and the Pelvis in Gynecology.
	No Results Available Other: Visceral therapy|Other: Placebo NRS|platforms|postural pattern by Halla-Wernhama-Littlejohna|pelvic type assessment|CromWell (measurement of oral dilation)|standarised questonarie by Kulesa-Morawiecka et al.|According to the Polish version of the questionnaire, the highest point value, i.e. 171, indicates the lowest rank in the quality of life assessment, while the lowest point value indicates the highest level of quality of life.|Female Sexual Function Index. Score: a value of 26 points or less indicates the presence of significantly clinical sexual dysfunction.|visceral techniques and placebo Female Not Applicable 200 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 305/23 September 1, 2026

Education Prof Dr. Cemil, T. and H. Organization Research (2023). Comparison of Vaginal Axis on MRI in Alternative Apical Prolapse Surgeries to Sacrocolpopexy.
	No Results Available Procedure: laparoscopic lateral suspension|Procedure: laparoscopic pectopexy|Procedure: Sacrospinous ligament fixation Vaginal axis|Vaginal distances|Prolapse symptoms, Colorectal-Anal Impact Questionnaire|Prolapse symptoms|Urinary Symptoms|Postoperative de novo dyspareunia|Sexual functions|Quality of life measures|Patient Global Impression of Improvement (PGI-I) Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Other E-10840098-772.02-4704 December 27, 2023

Education Prof Dr. Cemil, T. and H. Organization Research (2023). Vaginal Axis on Magnetic Resonance Imaging After Laparoscopic Pectopexy Surgery: a Controlled Study.
	No Results Available Procedure: laparoscopic pectopexy Anatomic Success|Urge Symptoms stres incontinence|Sexual functions Female Not Applicable 21 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 77 July 1, 2023

Edwards, L. M., et al. (2021). "A Systematic Review and Meta-Analysis of Risk Factors for Postpartum Depression Among Latinas." Maternal and Child Health Journal.
	OBJECTIVES: The purpose of this article was to describe the findings from a systematic review, quality review, and meta-analysis of risk factors for postpartum depression among adult Latinas in the United States. METHODS: Databases were searched from inception to May 2020 for studies published in English related to Latina/Hispanic mothers and risk factors of postpartum depression. Of 115 abstracts screened, 10 met the inclusion criteria for the review and meta-analysis. Eleven risk factors from these studies were included: acculturation, age, economic stress, education, marital status, number of children, prenatal depression, recent and remote intimate partner violence (IPV), general social support, and partner/father's social support. RESULTS: Partner/father's social support had a large effect size. Prenatal depression and recent IPV had medium effect sizes, while education, economic stress, general social support and remote IPV had small effect sizes. Negligible effect sizes were found for age, marital status, number of children, and acculturation. CONCLUSIONS: Prenatal depression, IPV, social support (general and from partner/father), economic stress and education are risk factors that should be screened for when working with perinatal Latinas. Future directions for clinical practice and research are discussed.

Edwin, A., et al. (2023). "Cost effectiveness of female overactive bladder syndrome therapy." Journal of Obstetrics and Gynaecology Research 49(Supplement 1): 135-136.
	Overactive bladder (OAB) syndrome is a chronic condition that has an impact on patients' daily activities and health-related quality of life (HRQL). First to fourth line therapy are often used following insufficient results with high rates of discontinuation. We aim to discuss how cost can be the cause of low persistence of the treatment of female OAB. This study systematically reviewed persistence/ adherence data in female OAB therapy. A search focused on the intersection of OAB therapy, persistence / adherence, and cost was conducted in MEDLINE along with Scopus and Google Scholar that published after 2010. Inclusion criteria are original articles of full-text length. Exclusion criteria are abstracts, review articles, and chapters from books. A total of 50 articles were included in the review. Results showed high rates of discontinuation, from 4%-40%, with 43%-83% discontinuing within the first 30 days and rise over time. The estimated average annual direct cost of OAB per patient are $500 to $3395. In addition, nursing home costs were estimated at $5.1 billion/year and it was estimated that work absenteeism related to OAB costs $1.2 billion/year. The low levels of persistence documented in this review reveal cause for concern about the balance of the cost effectiveness OAB therapy, especially in low resource country with limited coverage of health insurance. Strategies should be identified to increase persistence including the use of artificial intelligence to gain more cost effectiveness and minimal side effects over any existing traditional methods.

Efficace, F., et al. (2021). "Patient-Reported Outcomes as Independent Prognostic Factors for Survival in Oncology: Systematic Review and Meta-Analysis." Value in Health 24(2): 250-267.
	Objectives: Assessment of patient-reported outcomes (PROs) in oncology is of critical importance because it provides unique information that may also predict clinical outcomes. Method(s): We conducted a systematic review of prognostic factor studies to examine the prognostic value of PROs for survival in cancer. A systematic literature search was performed in PubMed for studies published between 2013 and 2018. We considered any study, regardless of the research design, that included at least 1 PRO domain in the final multivariable prognostic model. The protocol (EPIPHANY) was published and registered in the International Prospective Register of Systematic Reviews (CRD42018099160). Result(s): Eligibility criteria selected 138 studies including 158 127 patients, of which 43 studies were randomized, controlled trials. Overall, 120 (87%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival. Lung (n = 41, 29.7%) and genitourinary (n = 27, 19.6%) cancers were most commonly investigated. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies. The EORTC QLQ-C30 questionnaire was the most frequently used measure, and its physical functioning scale (range 0-100) the most frequent independent prognostic PRO, with a pooled hazard ratio estimate of 0.88 per 10-point increase (95% CI 0.84-0.92). Conclusion(s): There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. Further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.Copyright © 2020 ISPOR-The Professional Society for Health Economics and Outcomes Research

Eftekhar, M., et al. (2024). "Effectiveness of Autologous Platelet-Rich Plasma Therapy in Women with Repeated Implantation Failure: A Randomized Clinical Trial." International Journal of Fertility and Sterility 18(2): 162-166.
	Background: Platelet-rich plasma (PRP) therapy has been shown to enhance tissue regeneration by expressing sev-eral cytokines and growth factors (GFs). This study investigated the effect of intrauterine infusion of PRP as a non-invasive autologous GF on pregnancy outcomes in women with repeated implantation failure. Material(s) and Method(s): This randomized clinical trial was conducted to compare the pregnancy rates between two groups of women who were candidates for the frozen-thawed embryo transfer with a history of two or more implantation failures. The PRP group (n=33) was treated with hormone replacement therapy+0.5 cc to 1 cc PRP infused into the uterine cavity two days before the embryo transfer. The control group (n=33) was only treated with hormone replacement therapy. The endometrial preparation process was done similarly in both groups. The chemical, clinical, and ongoing pregnancy, and implantation rates were compared between the two groups. Result(s): Our results showed that the chemical pregnancy rate was not statistically higher in the PRP group in compari-son with the control group (36.4 vs. 24.2%). In addition, the clinical pregnancy, ongoing pregnancy, and implantation rates were higher in the PRP group than the control group; however, the difference between the two groups was not statistically significant. Conclusion(s): Administration of intrauterine PRP before embryo transfer in women with repeated implantation failure (RIF) does not affect assisted reproductive technology (ART) outcomes (registration number: IRCT2016090728950N3).Copyright © 2024, Royan Institute (ACECR). All rights reserved.

Egawa-Takata, T., et al. (2022). "Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma." Cancer Science 113(5): 1693-1701.
	This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment. The secondary end-points were progression-free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P =.005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2-year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).Copyright © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Eichler, S., et al. (2023). "A potent non-hormonal option for the treatment of postmenopausal vaginal dryness with high tolerability." Maturitas 173: 95-96.
	Genitourinary syndrome of menopause (GSM) is considered a chronic condition with urogenital implications caused by estrogen deficiency typically after onset of menopause. Vaginal dryness accompanied by burning and itching is one of the most prevalent and bothersome symptoms of GSM. Affected women suffer from reduced lubrication and, those who are sexually active, also from dyspareunia. Non-hormonal therapies, such as vaginal moisturizers or lubricants, are recommended as first-line treatments to achieve the relief of symptoms, while improving the quality of life. Due to emerging demand for pessary formulations, we evaluated the efficacy and tolerability of a non-hormonal pessary containing nourishing lipids and lactic acid. Therefore, a prospective, open-label clinical trial was performed, including 79 postmenopausal women with symptoms of vaginal dryness. The patients applied one pessary daily within the first week followed by two pessaries per week for the next 31 days. After 38 days of treatment, a treatment free period of 6 days completed the trial. Subjective symptoms of vaginal dryness, such as feeling of dryness, itching, burning and pain (unrelated and related to sexual intercourse), were assessed at every visit, while the objective vaginal health index (VHI) was only examined at beginning and end of treatment. Data regarding the impact on patients' quality of life, efficacy and tolerability were evaluated using various questionnaires. Our data show that symptoms of vulvovaginal dryness, itching, burning and pain as well as dyspareunia significantly decreased from baseline to end of treatment (day 38) and beyond. Quality of life assessed by DIVA (day-to day impact of vaginal aging) questionnaire, and VHI also clearly improved over the study period. The tolerability was rated as 'good' or 'very good' by most of the patients and by the investigator. No serious adverse events and only a low number of mild adverse events rated as related to the vaginal pessary were reported. Overall, this study identifies the investigated non-hormonal pessary as a potent option for the treatment of postmenopausal symptoms of vaginal dryness with a high tolerability. It can therefore be recommended as a first-line treatment that contributes to maintaining a healthy vaginal environment in postmenopausal women.Copyright © 2023

Eijkenboom, L., et al. (2022). "Strategies to safely use cryopreserved ovarian tissue to restore fertility after cancer: a systematic review." Reproductive Biomedicine Online 45(4): 763-778.
	Ovarian tissue cryopreservation and subsequent autotransplantation is a successful technique for fertility preservation in oncological patients. However, there are concerns regarding safety, as the graft may contain malignant cells that could lead to the reintroduction of cancer. To circumvent this problem several experimental strategies are being pursued. This systematic review was conducted to provide an overview of the strategies aiming to safely use cryopreserved human ovarian tissue to restore fertility after cancer. Thirty-one studies were included, covering five different experimental strategies: (i) in-vitro maturation of oocytes, (ii) constructing an artificial ovary as a scaffold for reseeding pre-antral follicles, (iii) purging strategies aimed at the eradication of contaminating malignant cells, (iv) maturation of oocytes by xenotransplantation, and (v) stem cell-based oogenesis. These strategies to circumvent the reintroduction of cancer cells through ovarian tissue autotransplantation are being developed, but so far have not reached the stage of clinical trials. Further research is required to establish their risks and effectiveness while the ethical aspects associated with these strategies also need to be discussed. Despite the fact that these experimental procedures are still under development, they might provide safe fertility restoration options for oncological patients in the future. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eisenberg, N., et al. (2021). "Short- and Long-Term Complications of Intraoperative Benign Ovarian Cyst Spillage: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(5): 957-970.
	Objective: To review short- and long-term complications associated with intraoperative rupture of benign ovarian cysts. Data Sources: The Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched using the following terms and their combinations: "spillage," "rupture," "leakage," "ovarian cyst," "teratoma," "dermoid," "operative," "surgery," "outcome." Methods of Study Selection: Randomized controlled and observational studies evaluating the operative outcomes of surgical treatment of ovarian cysts with intraoperative spillage compared with those of surgical treatment of ovarian cysts without spillage were included. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Tabulation, Integration, and Results: A total of 28 studies were included in the qualitative analysis and 12 in the quantitative analysis. Ovarian cyst diameter was not found to be associated with the risk for spillage (relative risk [RR] 0.75; 95% confidence interval [CI], -0.33 to 1.82). Intraoperative benign ovarian cyst rupture was not associated with adverse short- and long-term outcomes such as reoperation (RR 1.16; 95% CI, 0.39-3.48), infertility (RR 0.73; 95% CI, 0.15-3.63), transient fever (RR 3.22; 95% CI, 0.83-12.51), and readmission (RR 1.00; 95% CI, 0.33-2.98). However, intraoperative spillage was found to be associated with increased risk for benign recurrence (RR 3.1; 95% CI, 1.05-9.14). A subgroup analysis of the studies that included only dermoid cysts showed an association between intraoperative cyst rupture and postoperative chemical peritonitis (RR 9.36; 95% CI, 1.20-73.28). Conclusion(s): Intraoperative ovarian cyst spillage of a benign cyst is associated with limited adverse clinical outcomes. Although the surgical approach (minimally invasive vs open) should not be affected by the concern regarding an intraoperative cyst rupture, maximal efforts should be made to prevent intra-abdominal spillage.Copyright © 2020

Eisenlohr-Moul Tory, A., et al. (2022). "Effects of acute estradiol and progesterone on perimenstrual exacerbation of suicidal ideation and related symptoms: a crossover randomized controlled trial." Translational psychiatry 12(1): 528.
	Female suicide attempts peak peri-menstrually-around the onset of menses-when the ovarian steroids estradiol (E2) and progesterone (P4) fall rapidly. Given preclinical evidence that withdrawal from either E2 or P4 can provoke behaviors consistent with elevated suicide risk, we hypothesized that withdrawal from one or both of these steroids contributes to perimenstrual exacerbation of suicidal ideation (SI) and related symptoms. In a randomized, controlled, double-blind crossover experiment (NCT03720847), a transdiagnostic sample of naturally cycling, medically healthy psychiatric outpatients reporting past-month SI completed two conditions during two different 14-day experimental intervals (days 7-20 where the luteinizing hormone surge = day 0), separated by a monthlong washout cycle. In the E2 and P4 (EP) condition, participants received transdermal E2 (0.1 mg/day) plus oral micronized P4 (200 mg/day as 100 mg twice daily) to buffer perimenstrual steroid withdrawal. A matched placebo (PBO) condition allowed natural perimenstrual steroid withdrawal. Participants reported daily SI and planning (primary outcomes) and indices of depression (low mood, hopelessness), threat sensitivity (anxiety, perceived stress), executive functioning (difficulty concentrating, impulsivity), and social cognitive bias (rejection sensitivity, perceived burdensomeness). In baseline cycles, no participant met prospective criteria for DSM-5 premenstrual dysphoric disorder, but 59% met all criteria except full follicular symptom remission, and 93% showed the highest SI in the perimenstrual phase. Of 29 randomized, 28 were analyzed (14 EP-PBO, 14 PBO-EP). Experimental administration of E2 and P4 (relative to PBO) reduced perimenstrual exacerbation of SI, suicide planning, depression, hopelessness, perceived stress, rejection sensitivity, and perceived burdensomeness, particularly in the perimenstrual (natural E2 and P4 withdrawal) days. Further, delayed withdrawal from experimental E2 and P4 (but not PBO) recapitulated SI, hopelessness, and rejection sensitivity. Acute perimenstrual withdrawal from ovarian steroids may play a causal role in perimenstrual worsening of depression and SI. (© 2022. The Author(s).)

Ejaz, K., et al. (2022). "Use of gonadotropin-releasing hormone agonists for ovarian preservation in patients receiving cyclophosphamide for systemic lupus erythematosus: A meta-analysis." Lupus 31(14): 1706-1713.
	Background: Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy.; Methods: English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs).; Results: Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83-36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04-9.89).; Conclusion: Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC . Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation.

El Hajj, H., et al. (2021). "Rationale and study design of the CHIPPI-1808 trial: a phase III randomized clinical trial evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) for stage III ovarian cancer patients treated with primary or interval cytoreductive surgery." ESMO Open 6(2): 100098.
	BACKGROUND: Ovarian cancer remains the most lethal gynecologic malignancy with high recurrence rates. Because recurrence involves primarily the peritoneum, intraperitoneal chemotherapy is being evaluated as a new approach to treat microscopic peritoneal disease. One trial showed that cisplatin-paclitaxel intraperitoneal chemotherapy with intravenous paclitaxel improved survival but increased morbidity. Another trial reported a significant improvement in overall survival (OS) and disease-free survival (DFS) without increasing the morbidity (P = 0.76) or mortality rates (hazard ratio 0.67, P = 0.02) after adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreduction. The current trial aims to evaluate the impact of adding HIPEC to primary or interval cytoreductive surgery for epithelial ovarian cancer (EOC) on the efficacy, safety, treatment feasibility, and quality of life. PATIENTS AND METHODS: This is an international, multicenter, open-label, randomized (1 : 1), two-arm, phase III clinical trial that will enroll 432 patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III EOC. Patients are randomized to receive or not HIPEC with the standard of care. Inclusion criteria include patients with FIGO stage III EOC, Fallopian tube carcinoma or primary peritoneal cancer who undergo complete primary or interval cytoreduction. The primary objective is to assess DFS of the addition of HIPEC. Secondary objectives are the assessment of OS, safety, return to intended oncologic treatment, quality of life and the trade-off between efficacy and morbidity. CONCLUSIONS: The results might help extend the indications of HIPEC to include patients undergoing primary cytoreduction, providing a standardized protocol for HIPEC in EOC management and reliable information on the quality of life after adding HIPEC.

El Moujahed, L., et al. (2023). "Response to Ovarian Stimulation for Urgent Fertility Preservation before Gonadotoxic Treatment in BRCA -Pathogenic-Variant-Positive Breast Cancer Patients." Cancers 15(3).
	BRCA 1/2 pathogenic variants increase the risk of developing early and aggressive breast cancers (BC). For these patients, fertility potential can be directly affected by oncologic treatments. In addition, evidence indicates that BRCA -mutated women had a significant reduction in their ovarian reserve. In order to improve their chances of conception after the completion of cancer treatments, fertility preservation should be proposed before the administration of gonadotoxic drugs, ideally by oocyte vitrification after controlled ovarian hyperstimulation (COH). The present investigation aims to assess the ovarian response to COH in BRCA 1/2 -pathogenic-variant carriers diagnosed with BC. Patient characteristics and COH outcomes were compared between BRCA -positive ( n = 54) and BRCA -negative ( n = 254) patients. The number of oocytes recovered did not differ between the two groups. However, the oocyte maturation rate and the number of mature oocytes obtained (7 (4.5-11.5) vs. 9 (5-14) oocytes, p = 0.05) were significantly lower in the BRCA -mutated patients. Although individualized COH protocols should be discussed, BRCA -mutated patients would benefit from FP before BC occurs, in order to cope with the potential accelerated decline of their ovarian reserve, optimize the success rate of FP by repeating COH cycles, and to preserve the feasibility of PGT-M by collecting a large amount of eggs.

El Sabeh, M., et al. (2021). "Simvastatin Inhibits Wnt/β-Catenin Pathway in Uterine Leiomyoma." Endocrinology 162(12).
	The Wnt/β-catenin pathway is upregulated in uterine leiomyomas, the most common benign tumors in the female reproductive tract. Simvastatin is an antihyperlipidemic drug, and previous in vitro and in vivo reports showed that it may have therapeutic effects in treating leiomyomas. The objective of this study was to examine the effects of simvastatin on the Wnt/β-catenin signaling pathway in leiomyoma. We treated primary and immortalized human leiomyoma cells with simvastatin and examined its effects using quantitative real-time polymerase chain reaction, Western blotting, and immunocytochemistry. We also examined the effects using human leiomyoma tissues from an ongoing randomized controlled trial in which women with symptomatic leiomyoma received simvastatin (40 mg) or placebo for 3 months prior to their surgery. The results of this study revealed that simvastatin significantly reduced the expression of Wnt4 and its co-receptor LRP5. After simvastatin treatment, levels of total β-catenin and its active form, nonphosphorylated β-catenin, were reduced in both cell types. Additionally, simvastatin reduced the expression of Wnt4 and total β-catenin, as well as nonphosphorylated β-catenin protein expression in response to estrogen and progesterone. Simvastatin also inhibited the expression of c-Myc, a downstream target of the Wnt/β-catenin pathway. The effect of simvastatin on nonphosphorylated-β-catenin, the key regulator of the Wnt/β-catenin pathway, was recapitulated in human leiomyoma tissue. These results suggest that simvastatin may have a beneficial effect on uterine leiomyoma through suppressing the overactive Wnt/β-catenin pathway.

Elansary, M., et al. (2023). "Effect of Immediate Referral vs a Brief Problem-solving Intervention for Screen-Detected Peripartum Depression: A Randomized Clinical Trial." JAMA Network Open 6(5): E2313151.
	Importance: The US Preventive Services Task Force recommends screening adults for depression in settings with programs in place to ensure receipt of appropriate care. Best practices regarding how to ensure such care are unknown, particularly for pregnant and postpartum persons. Objective(s): To compare the effectiveness of 2 strategies for the initial management of screen-detected peripartum depressive symptoms. Design, Setting, and Participant(s): This randomized comparative effectiveness trial was performed from February 1, 2018, to June 30, 2020, at the prenatal clinic, postpartum unit, and pediatric clinic within an urban safety-net hospital. Participants included peripartum persons with positive depression screen results. Data were analyzed from July 6, 2020, to September 21, 2022, based on intention to treat. Intervention(s): Engagement-focused care coordination (EFCC), which used shared decision-making and motivational techniques to refer patients to outside mental health services, and problem-solving education (PSE), a brief cognitive-behavioral program delivered at the screening site. Main Outcomes and Measures: The primary outcome consisted of severity of depressive symptoms; secondary outcomes included severity of anxiety symptoms and engagement with care, each measured bimonthly over 12 months. Rates of symptom elevations were modeled using negative binomial regression; rates of symptom trajectories were modeled using treatment x time interactions. Result(s): Among the 230 participants (mean [SD] age, 29.8 [5.8] years), 125 (54.3%) were Black and 101 (43.9%) were Hispanic or Latina. At baseline, 117 participants (50.9%) reported at least moderately severe depressive symptoms (Quick Inventory of Depressive Symptomatology score >=11), and 56 (24.3%) reported clinically significant anxiety symptoms (Beck Anxiety Inventory score >=21). Across 6 assessment time points, the mean (SD) number of moderately severe depressive symptom episodes in EFCC was 2.2 (2.2), compared with 2.2 (2.1) in PSE, for an adjusted rate ratio (aRR) of 0.95 (95% CI, 0.77-1.17). The mean (SD) number of anxiety symptom elevations in EFCC was 1.1 (1.8), compared to 1.1 (1.6) in PSE, for an aRR of 0.98 (95% CI, 0.69-1.39). There were significant treatment x time interactions relative to mean depressive symptom scores (-0.34 [95% CI, -0.60 to -0.08]; P =.009 for interaction term), favoring EFCC. There were no differences in engagement with care. Conclusions and Relevance: In this randomized comparative effectiveness trial, there were no differences in depressive or anxiety symptom burden across comparators; however, the evidence suggested improved depressive symptom trajectory with immediate referral. Further work is necessary to guide approaches to management following depression screening for peripartum persons. Trial Registration: ClinicalTrials.gov Identifier: NCT03221556.Copyright © 2023 American Medical Association. All rights reserved.

Elassall Gena, M., et al. (2022). "Levonorgestrel-releasing intrauterine system versus systemic progestins in management of endometrial hyperplasia: A systemic review and meta-analysis." Journal of Gynecology Obstetrics and Human Reproduction 51(8): 102432.
	Introduction: Endometrial hyperplasia is associated with varying risk of endometrial cancer. The aim of this review is to assess effectiveness of levonorgestrel-releasing intrauterine system (LNG-IUS), compared to systemic progestins, in management of endometrial hyperplasia MATERIALS AND METHODS: A search on studies comparing LNG-IUS to systemic progestins was conducted on Scopus, Web of science, Cochrane, PubMed and Embase databases, from the date of inception to September 20 th , 2020. Studies were excluded if they were non-comparative, animal studies, review articles, case reports, case series, and conference papers. Primary outcomes include resolution/regression rate, failure rate, and hysterectomy rate. Analysis was pooled using random effect model and was expressed as pooled odds ratios (OR) and 95% confidence interval (CI). Quality assessment was performed using Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) assessment tool. MOGGE Meta-analysis Matrix was used to illustrate multiple subgroup analyses.; Results: Out of 341 studies retrieved from literature search, 12 were eligible. LNG-IUS yielded significantly higher resolution/regression rate (91.3% vs 68.6%, OR 3.42, 95% CI 1.86-6.30). Failure and hysterectomy rates were significantly lower in LNG-IUS group compared to systemic progestins' group (19.2% vs. 32.3%, OR 0.34, 95% CI 0.20-0.57 and 9.3% vs. 24.1%, OR 0.41, 95% CI 0.29-0.57, respectively). Subgroup analysis of studies including complex hyperplasia only did not show significant difference in resolution/regression rate was not statistically significant.; Conclusion: LNG-IUS is associated with high success rate in management of women with endometrial hyperplasia. However, specific effectiveness of LNG-IUS on more advanced histologic subtypes is less studied.; Competing Interests: Declaration of Competing Interest None (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Elasy, A. N., et al. (2022). "Vaginal misoprostol versus combined intracervical foley's catheter and oxytocin infusion for second trimester pregnancy termination in women with previous caesarean sections: a randomised control trial." Journal of Obstetrics and Gynaecology 42(7): 2962‐2969.
	Second trimester pregnancy termination has been reported to be associated with 3–5 times higher maternal morbidity and mortality risks more than first trimester termination. Medical methods had been thoroughly assessed and it is considered the anchor of the safe abortion care. Howevere, there is no global agreement regarding the ideal method for induction of the second trimester abortion in a scarred uterus. The aim of this study was to achieve vaginal expulsion in an expeditious manner with less maternal complications. A total of 158 women having, a history of previous caesarean section undergoing second trimester pregnancy termination, were randomly allocated into group (1) vaginal misoprostol group (n = 79) or group (2) combined intracervical foley’s catheter plus intravenous oxytocin infusion group (n = 79). The primary endpoint was complete fetal expulsion. Meanwhile, secondary outcomes were the rates of maternal complications, in terms of the need for surgical evacuation of retained product of conception (ERPOC), severe haemorrhage, uterine rupture, blood transfusion, cervical laceration, diarrhoea, vomiting and fever. The registration number of this trial https://clinicaltrials.gov/ct2/show/NCT04501809. This study showed that the combined use of intracervical foley’s catheter and oxytocin is an effective, and safe alternative to vaginal misoprostol for termination of the second trimester pregnancy in women having a previous caesarean delivery.Impact statementWhy was this study conducted? The purpose of this study is to achieve an expeditious delivery for second trimester pregnancy termination in a scarred uterus by combined mechanical and pharmacological methods without significant morbidity. Physicians should balance the benefit of achieving vaginal exlpusion in an expeditious manner versus the risk of uterine rupture or any other maternal complications. What does this add to what is known? This study showed that a combined mechanical and pharmacolohical approach for second trimester termination of pregnancy has comparable efficacy and safety to vaginal misoprostol which is more affordable to the low resources countries where termination of pregnancy in a scarred uterus still has an increased maternal morbidity. What is the implication of this study on clinical practice? The combined use of intracervical foley’s catheter with intravenous oxytocin infusion is a safer option than vaginal misoprostol with less serious maternal complications.

El-Azab Ahmed, S. and W. Siegel Steven (2019). "Sacral neuromodulation for female pelvic floor disorders." Arab Journal of Urology 17(1): 14-22.
	Objective : To systematically review available studies on the effectiveness and safety of sacral neuromodulation (SNM) in women with various pelvic floor disorders not responding to more conservative treatment, as SNM is indicated in such women. Methods : Data source: We did a systematic review through the PubMed and the Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from 1998 to 2018 in English using the keywords 'Sacral Neuromodulation' and 'Sacral Nerve Stimulation'. Study selection : Randomised controlled trials and prospective studies were selected, with a minimum sample size of 20 patients and ≥6 months of follow-up. Results : We identified 19 articles. A ≥50% reduction in symptoms qualifies the patient for a permanent implant. Several advances have been introduced into SNM to decrease the invasiveness of the procedure, including a smaller implantable pulse generator battery (improved comfort) and better localisation of the lead wire (improved outcome). The literature reports success for overactive bladder (OAB) to range between 56% and 68% (up to 80%). We report a 5-year therapeutic success rate of 67%. In our previous studies, 38% of our patients with urge urinary incontinence achieved complete continence at 60-months follow-up, with a therapeutic response rate of 57%. Effectiveness in patients with urinary retention and faecal incontinence are about 70% and 85%, respectively. Effectiveness in interstitial cystitis/bladder pain syndrome appears to be lower compared with OAB. Conclusion : SNM is a safe and effective therapy for women with various pelvic floor disorders. Abbreviations: BONT: botulinum toxin; FDA: USA Food and Drug Administration; FS: Fowler's syndrome; FI: faecal incontinence; IC/BPS: interstitial cystitis/bladder pain syndrome; ICIQ-OABqol: International Consultation on Incontinence Modular Questionnaire-Overactive Bladder Symptoms Quality of Life; INS: implantable neurostimulator; OAB: overactive bladder; PET: positron emission tomography; PNE: peripheral nerve evaluation; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTNM: posterior tibial nerve modulation; PVR: post-void residual urine; QoL: quality of life; RCT: randomised controlled trial; SNM: sacral neuromodulation; (U)UI: (urgency) urinary incontinence.

Elderbashy, M. S., et al. (2021). "High intensity interval training for cardiometabolic disease prevention in polycystic ovarian syndrome females: Literature review." Journal of Cardiovascular Disease Research 12(5): 937-943.
	Aims: Thisnarrative review aims to examine the effect of high intensity interval training (HIIT) for prevention ofcardiometabolic disease in females with polycystic ovarian syndrome (PCOS). Also,itaims to provide a framework for future research to be able to formulate more comprehensive, lifestyle-centered guidelines intreating women with PCOS. Method(s): A literature search was elicited in PEDro, Cochrane library, PubMed, and Google Scholar databases with the keywords"Physical therapy modalities", "PCOS", "HIIT", "Exercise protocol","Cardiometabolic Risk", "Insulin Resistance (IR)" and "Metabolic syndrome".Reviewed literature was analyzed and summarizeddescriptively. Result(s): HIIT can lower IR and improve metabolic syndrome when performed in regular basis. Conclusion(s): HIIT is effective in prevention of cardiometabolic disease in polycystic ovarian females.Copyright © 2021 EManuscript Technologies. All rights reserved.

Eleftheria, K., et al. (2021). "The role of maternal physical activity on in vitro fertilization outcomes: a systematic review and meta-analysis."
	
Eleje George, U., et al. (2020). "Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies." The Cochrane Database of Systematic Reviews 9: CD012871.
	Background: Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments.; Objectives: To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of 'short cervix' and/or physical examination. History-indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination.; Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies.; Selection Criteria: We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster-RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi-RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross-over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies.; Data Collection and Analysis: Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout.; Main Results: We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone - this study did provide useable data for this review (and the study authors also provided additional data on request) but meta-analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low-certainty evidence); perinatal loss (data for miscarriage and stillbirth only - data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low-certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low-certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death.; Authors' Conclusions: Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17-alpha-hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest. (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

El-Ghazzi, N., et al. (2023). "[New drug arrival : Pembrolizumab as second-line treatment in MSI-H/dMMR endometrial, colorectal, gastric, intestinal and biliary cancers]." Bulletin du cancer 110(1): 11-13.
	Nouvelles AAM : pembrolizumab en deuxième ligne des tumeurs métastatiques MSI-H/dMMRNew drug arrival : Pembrolizumab as second-line treatment in MSI-H/dMMR endometrial, colorectal, gastric, intestinal and biliary cancers Le système de réparation des mésappariements (ou MisMatch Repair, MMR ) maintient l’intégrité de l’ADN en corrigeant avec une haute fidélité les erreurs de réplication de l’ADN telles que les insertions, les délétions et les mésappariements de bas...

El-Hashimi, D. and M. Gorey Kevin (2019). "Yoga-specific enhancement of quality of life among women with breast cancer: Systematic review and exploratory meta-analysis of randomized controlled trials." Journal of Evidence-Based Integrative Medicine 24.
	Physical activities during and after cancer treatment have favorable psychosocial effects. Increasingly, yoga has become a popular approach to improving the quality of life (QoL) of women with breast cancer. However, the extant synthetic evidence on yoga has not used other exercise comparison conditions. This meta-analysis aimed to systematically assess yoga-specific effects relative to any other physical exercise intervention (eg, aerobics) for women with breast cancer. QoL was the primary outcome of interest. Eight randomized controlled trials with 545 participants were included. The sample-weighted synthesis at immediate post-intervention revealed marginally statistically and modest practically significant differences suggesting yoga's potentially greater effectiveness: d = 0.14, P = .10. However, at longer term follow-up, no statistically or practically significant between-group difference was observed. This meta-analysis preliminarily demonstrated that yoga is probably as effective as other exercise modalities in improving the QoL of women with breast cancer. Both interventions were associated with clinically significant improvements in QoL. Nearly all of the yoga intervention programs, however, were very poorly resourced. Larger and better controlled trials of well-endowed yoga programs are needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Elias, M. H., et al. (2023). "HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review." Biology 12(3).
	Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR "homeobox A10" OR "HOXA-10" OR HOX1) AND ("DNA methylation" OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis.

Eliezer, D., et al. (2019). "Alpha blockers for treating functional daytime urinary incontinence in children." Cochrane Database of Systematic Reviews(4).
	This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of alpha blockers for treating functional daytime urinary incontinence in children.

Elkind-Hirsch, K. E., et al. (2021). "Exenatide, dapagliflozin or phentermine/topiramate differentially affect metabolic profiles in polycystic ovary syndrome." The Journal of Clinical Endocrinology and Metabolism 106(10): 3019-3033.
	CONTEXT: Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and co-administered (EQW/DAPA), DAPA/extended release metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. RESEARCH DESIGN AND METHODS: Non-diabetic women (n=119; 18-45y) with BMI>30 <45 and PCOS (NIH criteria) were randomized in a single-blind fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000mg XR daily) or PHEN (7.5 mg)/TPM (46mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures and body composition evaluated by dual-energy X-ray absorptiometry (DXA). Oral glucose tolerance tests (OGTT) were done to assess glycemia, mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI) and lipid profiles were measured in the fasting sample. RESULTS: EQW/DAPA and PHEN/TPM resulted in the most loss of weight, total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI and IS. Reductions in fasting glucose, testosterone, FAI and BP were seen with all drugs. CONCLUSION: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

Elliott, J., et al. (2023). "Guideline No. 444: Hirsutism: Evaluation and Treatment." Journal of Obstetrics and Gynaecology Canada 45(12): 102272.
	Objective: This guideline reviews the etiology, diagnosis, evaluation, and treatment of hirsutism. Target Population: Women with hirsutism. Options: Three approaches to management include: 1) mechanical hair removal; 2) suppression of androgen production; and 3) androgen receptor blockade. Outcome(s): The main limitations of the management options include the adverse effects, costs, and duration of treatment. Benefits, Harms, and Costs: Implementation of the recommendations in this guideline may improve the management of hirsutism in women with this condition. Adverse effects and a potential long duration of treatment are the main drawbacks to initiating treatment, as is the possibility of significant financial costs for certain treatments. Evidence: A comprehensive literature review was updated to April 2022, following the same methods as for the prior Society of Obstetricians and Gynaecologists of Canada (SOGC) Hirsutism guidelines. Results were restricted to systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. There were no date limits, but results were limited to English- or French-language materials. Validation Methods: The authors rated the quality of evidence and strength of recommendations using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, along with the option of designating a recommendation as a "good practice point." See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). Intended Audience: Primary care providers, family medicine physicians, obstetricians and gynaecologists, reproductive endocrinologists and others who manage the care of patients with hirsutism. Tweetable Abstract: Management of hirsutism involves a 3-pronged approach of mechanical hair removal, suppression of androgen production, and androgen receptor blockade. SUMMARY STATEMENTS: 1. The modified Ferriman-Gallwey score can be used in the assessment of hirsutism to help quantify the problem and assess the response to treatment. Cut-off scores defining hirsutism will vary by racial background. Modified Ferriman-Gallwey scores from 3 to 15 represent mild hirsutism, 16-25 represent moderate hirsutism, and >25 indicate severe hirsutism (moderate). 2. Hyperandrogenism in women with polycystic ovary syndrome may result from several mechanisms, including insulin resistance, hyperinsulinemia, elevated luteinizing hormone-related increases in theca cell androgen production, and increased adrenal androgen output. (high). 3. Non-classical congenital adrenal hyperplasia often presents with hirsutism and has a similar clinical picture as polycystic ovary syndrome. However, the prevalence of non-classical congenital adrenal hyperplasia is very low outside of specific high-risk ethnic groups (high). 4. Hirsutism can be classified into 1 of 3 groups based on etiology: hyperandrogenic hirsutism (including polycystic ovarian syndrome, non-classical congenital adrenal hyperplasia, or androgen-secreting tumours), non-androgenic hirsutism (including medication-induced hirsutism), and idiopathic hirsutism (moderate). 5. Polycystic ovary syndrome is the most common cause of hirsutism, with idiopathic hirsutism being the second most common (high). 6. Most patients with hirsutism have normal androgen levels. That said, high androgen levels should be investigated immediately, as some impacts will be permanent, such as voice changes and clitoromegaly (high). 7. Hirsutism is not a diagnosis, but a symptom or sign, and an underlying etiology should be sought (high). 8. The most effective therapy for hirsutism is multimodal and combines physical hair removal techniques with medical therapies. At least six months of medical therapy is required to see a significant improvement in hirsutism. Unfortunately, many permanent physical hair removal procedures are considered cosmetic and the costs can be a barrier to treatment (moderate). 9. Hair growth tends to recur after stopping medical therapy, while laser hair removal, intense pulsed light, and electrolysis produce permanent hair reduction (moderate). RECOMMENDATIONS: 1. Patients presenting with hirsutism should be evaluated with a focused history taking, physical examination with anthropometric measurements, and appropriate investigations to differentiate between the possible etiologies (strong, moderate). 2. Patients with moderate to severe hirsutism should undergo blood testing to determine total testosterone and sex hormone-binding globulin levels; however, the benefit of testing in mild hirsutism is questionable. Additional testing is indicated for patients with irregular cycles and signs of hyperandrogenism or other endocrinopathies (conditional, low). 3. Patients with hyperandrogenic hirsutism should have serum levels of dehydroepiandrosterone sulfate and 17-hydroxyprogesterone measured (strong, moderate). 4. Referral for evaluation by a medical or reproductive endocrinologist (or another practitioner with similar expertise) is indicated in the presence of 1) virilization; 2) serum testosterone or dehydroepiandrosterone sulfate levels more than twice the upper limit of normal; 3) signs or symptoms of Cushing syndrome; or 4) early follicular phase serum 17-hydroxyprogesterone levels >6 nmol/L (strong, high). 5. Therapy should be offered to all patients with hirsutism who desire treatment (good practice point). 6. Combined hormonal contraceptives should be offered as first-line therapy if there are no contraindications (strong, high). 7. Mechanical hair removal and/or topical treatments can be offered as first-line therapy or as an adjuvant to medical therapy (strong, high). 8. Antiandrogens can be considered as monotherapy or in addition to combined hormonal contraceptives to enhance efficacy (strong, high). 9. Patients on antiandrogens require an effective method of contraception and should be counselled regarding the risk of feminization of a male fetus if pregnancy were to occur (good practice point).Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Societe des obstetriciens et gynecologues du Canada

Elsan (2021). Efficacy of the Photobiomodulation on the Pelvi-perineal Pain in Immediate Post-partum Situation.
	In this study, the investigators propose to evaluate the benefit of an innovative analgesic treatment in the immediate postpartum period using photobiomodulation (PBM) by evaluating pain using a Visual Analog Scale. PBM, discovered in the 1950s, uses the properties of light. The PBM corresponds to all the non-thermal and non-cytotoxic biological effects caused by the exposure of tissues to light sources in the visible and near-infrared range. More precisely, certain wavelengths of the light spectrum (red-infrared) lead to a cascade of biological effects within the cell: reduction of pain, regulation of inflammation and acceleration of the healing process. The objective of this study is to analyze the possibility of replacing chemical medication by a non-invasive, painless technology in patients who have just given birth. This technology is already used for anti-inflammatory and analgesic actions in indications such as stomatology, rheumatology, post-operation and traumatology. This is part of the field of NMIs (non-medicinal interventions).

Elsea, D., et al. (2022). "Correction to: Cost-Effectiveness Analysis of Olaparib in Combination with Bevacizumab Compared with Bevacizumab Monotherapy for the First-Line Maintenance Treatment of Homologous Recombination Deficiency-Positive Advanced Ovarian Cancer." PharmacoEconomics - open 6(6): 899.
	
El-Swaify Seif, T., et al. (2023). "Can fluorescence-guided surgery improve optimal surgical treatment for ovarian cancer? A systematic scoping review of clinical studies." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(4): 549-561.
	Background: The predicament of achieving optimal surgical intervention faced by surgeons in treating ovarian cancer has driven research into improving intra-operative detection of cancer using fluorescent materials.; Objective: To provide a literature overview on the clinical use of intra-operative fluorescence-guided surgery for ovarian cancer, either for cytoreductive surgery or sentinel lymph node (SLN) biopsy.; Methods: The systematic review included studies from June 2002 until October 2021 from PubMed, Web of Science, and Scopus as well as those from a search of related literature. Studies were included if they investigated the use of fluorescence-guided surgery in patients with a diagnosis of ovarian cancer. Authors charted variables related to study characteristics, patient demographics, baseline clinical characteristics, fluorescence-guided surgery material, and treatment details, and surgical, oncological, and survival outcome variables. After screening 2817 potential studies, 24 studies were included.; Results: Studies investigating the role of fluorescence-guided surgery to visualize tumor deposits or SLN biopsy included the data of 410 and 118 patients, respectively. Six studies used indocyanine green tracer with a mean SLN detection rate of 92.3% with a pelvic and para-aortic detection rate of 94.8% and 96.7%, respectively. The sensitivity, specificity, and positive predictive value for micrometastases detection of OTL38 and 5-aminolevulinc acid at time of cytoreduction were 92.2% vs 79.8%, 67.3% vs 94.8%, and 55.8% vs 95.8%, respectively.; Conclusion: Fluorescence -guided surgery is a technique that may improve the detection rate of micrometastases and SLN identification in ovarian cancer. Further research is needed to establish whether this will lead to improved patient outcomes.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Elterman, D., et al. (2021). "A prospective, multicenter, international study to explore the effect of three different amplitude settings in female subjects with urinary urge incontinence receiving interstim therapy." Neurourology and Urodynamics 40(3): 920‐928.
	AIMS: The aim of this study is to evaluate the effect of sub‐sensory amplitude settings of sacral neuromodulation therapy on overactive bladder symptoms in subjects with urinary urge incontinence. METHODS: Subjects who qualified for a neurostimulator device implant were randomized to one of three amplitude settings (50% of sensory threshold [ST], 80% of ST, and ST). Subjects completed urinary voiding diaries (3‐day), International consultation on incontinence modular questionnaire‐overactive bladder symptoms quality of life questionnaire, and patient global impression of improvement (PGI‐I) to assess change in voiding symptoms and quality of life (QoL) from baseline through 12 weeks. RESULTS: Forty‐eight subjects had a successful test stimulation, 46 were implanted with a neurostimulator device and 43 completed the 12‐week follow‐up visit. The change from baseline to 12 weeks is ‐3.0 urinary incontinence (UI) episodes/day (95% confidence interval [CI]: ‐4.4 to ‐1.7) for the 50% of sensory threshold group, ‐2.9 UI episodes/day (95% CI: ‐4.7 to ‐1.2) for 80% of sensory threshold group, and ‐3.6 UI episodes/day (95% CI: ‐5.2 to ‐1.9) for the sensory threshold group. In each randomized group, improvements were observed in health‐related QoL, its subscales, and symptom interference. Subjects across all three randomization groups reported on the PGI‐I that their bladder condition was better at 12 weeks compared to before they were treated with InterStim therapy. CONCLUSION: These findings provide insights into possible advancements in the postimplantation phase of therapy with potential for improved patient comfort and increased device longevity.

Elterman, D., et al. (2022). "Prospective, multicenter study to evaluate performance and safety of a re-engineered temporary lead for InterStimTM therapy evaluation." Neurourology and Urodynamics 41(8): 1731-1738.
	Aims: The basic evaluation or percutaneous nerve evaluation (PNE) is a method to assess pre-implantation therapeutic response in patients considering sacral neuromodulation for the treatment of refractory overactive bladder. A new PNE lead with a more robust design and greater distensibility designed to reduce the possibility of lead migration has recently been introduced to the market. The aim of this prospective, multicenter, global, postmarket study was to evaluate the clinical performance and safety of the new InterStim PNE lead with the foramen needle. Method(s): Patients with overactive bladder were enrolled in this study. The primary objective of this study was to determine the proportion of subjects who demonstrated motor or sensory response(s) during lead placement using the InterStim PNE lead. Additional measures included the Patient Global Impression of Improvement (PGI-I), patient satisfaction at the end of therapy evaluation, and change in bladder symptoms from baseline to the end of therapy evaluation (1-week follow-up visit). Result(s): One-hundred and ten subjects met the inclusion and exclusion criteria and underwent a lead implant procedure. Of those, 108 had a successful procedure and 107 completed the 1-week follow-up visit. Ninety-nine percent of subjects (109/110) had a motor or sensory response during needle placement (95% confidence interval [CI]: 95%-100%) and 97% of subjects (107/110) had a motor or sensory response during lead placement (95% CI: 92%-99%). The majority of subjects (88%, 95/108) reported their bladder condition was better at the follow-up visit compared to before the PNE implant procedure, as reported in PGI-I. Subjects reported being satisfied with how the therapy impacted their voiding symptoms (82%, 88/108) and that they would recommend this therapy (87%, 94/108) to other patients. Symptom improvement was demonstrated with urinary urge incontinence subjects having an average of 4.2 +/- 3.4 urinary incontinence episodes/day at baseline and 2.2 +/- 2.5 at follow-up, and urinary frequency subjects having an average of 12.5 +/- 4.4 voids/day at baseline and 10.5 +/- 4.3 voids/day at follow-up. Lead removal was deemed to be easy and safe by the implanting physician, with a total of three adverse device effects in 3/110 subjects. No event was categorized as serious and all were resolved without sequelae. Conclusion(s): The updated InterStim PNE lead with a more robust design and greater distensibility designed to reduce migration was shown to have a high rate of motor or sensory response during lead placement. Furthermore, subjects reported high rates of global improvements and amelioration of symptoms, and the lead was easy to remove with minimal morbidity.Copyright © 2022 Wiley Periodicals LLC.

Elwood, P. C., et al. (2021). "Aspirin and cancer survival: A systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers." ecancermedicalscience 15: 1258.
	Background: Despite the accumulation of research papers on aspirin and cancer, there is doubt as to whether or not aspirin is an acceptable and effective adjunct treatment of cancer. The results of several randomised trials are awaited, and these should give clear evidence on three common cancers: colon, breast and prostate. The biological effects of aspirin appear likely however to be of relevance to cancer generally, and to metastatic spread, rather than just to one or a few cancers, and there is already a lot of evidence, mainly from observational studies, on the association between aspirin and survival in a wide range of cancers. Aim(s): In order to test the hypothesis that aspirin taking is associated with an increase in the survival of patients with cancer, we conducted a series of systematic literature searches to identify clinical studies of patients with cancer, some of whom took aspirin after having received a diagnosis of cancer. Result(s): Three literature searches identified 118 published observational studies in patients with 18 different cancers. Eighty-one studies report on aspirin and cancer mortality and 63 studies report on all-cause mortality. Within a total of about a quarter of a million patients with cancer who reported taking aspirin, representing 20%-25% of the total cohort, we found aspirin to be associated with a reduction of about 20% in cancer deaths (pooled hazard ratio (HR): 0.79; 95% confidence intervals: 0.73, 0.84 in 70 reports and a pooled odds ratio (OR): 0.67; 0.45, 1.00 in 11 reports) with similar reductions in all-cause mortality (HR: 0.80; 0.74, 0.86 in 56 studies and OR: 0.57; 0.36, 0.89 in seven studies). The relative safety of aspirin taking was examined in the studies and the corresponding author of every paper was written to asking for additional information on bleeding. As expected, the frequency of bleeding increased in the patients taking aspirin, but fatal bleeding was rare and no author reported a significant excess in fatal bleeds associated with aspirin. No author mentioned cerebral bleeding in the patients they had followed. Conclusion(s): There is a considerable body of evidence suggestive of about a 20% reduction in mortality in patients with cancer who take aspirin, and the benefit appears not to be restricted to one or a few cancers. Aspirin, therefore, appears to deserve serious consideration as an adjuvant treatment of cancer, and patients with cancer, and their carers, have a right to be informed of the available evidence.Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Elyashiv, O., et al. (2024). "The Poor Prognosis of Acquired Secondary Platinum Resistance in Ovarian Cancer Patients." Cancers 16(3).
	Objective: The goal of this study was to evaluate response to treatment and survival in epithelial ovarian cancer patients with acquired secondary platinum resistance (SPR) compared to patients with primary platinum resistance (PPR).; Methods: Patients were categorized as PPR (patients with disease recurrence occurring during or <6 months after completing first-line platinum-based chemotherapy) and SPR (patients with previously platinum-sensitive disease that developed platinum resistance on subsequent treatments). Clinico-pathological variables and treatment outcomes were compared.; Results: Of the 118 patients included in this study, 60 had PPR and 58 developed SPR. The SPR women had a significantly higher rate of optimal debulking during their upfront and interval operations, significantly lower CA-125 levels during their primary treatment, and a significantly higher complete and partial response rate to primary chemotherapy. Once platinum resistance appeared, no significant difference in survival was observed between the two groups. The median PFS was 2 months in the PPR group and 0.83 months in the SPR group ( p = 0.085). Also, no significant difference was found in post-platinum-resistant relapse survival, with a median of 17.63 months in the PPR and 20.26 months in the SPR group ( p = 0.515).; Conclusions: Platinum resistance is an important prognostic factor in women with EOC. Patients with SPR acquire the same poor treatment outcome as with PPR. There is a great need for future research efforts to discover novel strategies and biological treatments to reverse resistance and improve survival.

Elyashiv, O., et al. (2021). "ICON 9-an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(1): 134-138.
	BACKGROUND: Two novel biological agents-cediranib targeting angiogenesis, and olaparib targeting DNA repair processes-have individually led to an improvement in ovarian cancer control. The aim of ICON9 is to investigate the combination of cediranib and olaparib maintenance in recurrent ovarian cancer following platinum-based therapy. PRIMARY OBJECTIVE: To assess the efficacy of maintenance treatment with olaparib in combination with cediranib compared with olaparib alone following a response to platinum-based chemotherapy in women with platinum-sensitive ovarian, fallopian tube or peritoneal cancer during first relapse. STUDY HYPOTHESIS: Maintenance therapy with cediranib and olaparib in combination is associated with improved patient outcomes compared with olaparib alone. TRIAL DESIGN: International phase III randomized controlled trial. Following a response to platinum-based chemotherapy patients are randomized 1:1 to either oral olaparib and cediranib (intervention arm) or oral olaparib alone (control arm). MAJOR INCLUSION CRITERIA: Patients with a known diagnosis of high grade serous or endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing more than 6 months after first-line platinum-based chemotherapy, who have responded to second-line platinum-based chemotherapy. PRIMARY ENDPOINTS: Progression-free and overall survival. Co-primary endpoints to be assessed using a fixed-sequence gatekeeping approach: (1) progression-free survival, all patients; (2) progression-free survival, BRCA wild type; (3) overall survival, all patients; (4) overall survival, BRCA wild type. SAMPLE SIZE: 618 patients will be recruited. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03278717.

Embaby, A., et al. (2023). "WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study." Gynecologic Oncology 174: 239-246.
	Objective: In the first part of this phase II study (NCT01164995), the combination of carboplatin and adavosertib (AZD1775) was shown to be safe and effective in patients with TP53 mutated platinum-resistant ovarian cancer (PROC). Here, we present the results of an additional safety and efficacy cohort and explore predictive biomarkers for resistance and response to this combination treatment.; Methods: This is a phase II, open-label, non-randomized study. Patients with TP53 mutated PROC received carboplatin AUC 5 mg/ ml·min intravenously and adavosertib 225 mg BID orally for 2.5 days in a 21-day cycle. The primary objective is to determine the efficacy and safety of carboplatin and adavosertib. Secondary objectives include progression-free survival (PFS), changes in circulating tumor cells (CTC) and exploration of genomic alterations.; Results: Thirty-two patients with a median age of 63 years (39-77 years) were enrolled and received treatment. Twenty-nine patients were evaluable for efficacy. Bone marrow toxicity, nausea and vomiting were the most common adverse events. Twelve patients showed partial response (PR) as best response, resulting in an objective ORR of 41% in the evaluable patients (95% CI: 23%-61%). The median PFS was 5.6 months (95% CI: 3.8-10.3). In patients with tumors harboring CCNE1 amplification, treatment efficacy was slightly but not significantly better.; Conclusions: Adavosertib 225 mg BID for 2.5 days and carboplatin AUC 5 could be safely combined and showed anti-tumor efficacy in patients with PROC. However, bone marrow toxicity remains a point of concern, since this is the most common reason for dose reductions and dose delays.; Competing Interests: Declaration of Competing Interest A list with conflicts of interest of all authors will be provided. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Emerson, M., et al. (2023). "A systematic review and exploration of smartphone app interventions for perinatal depression with case study." Current Treatment Options in Psychiatry 10(3): 136-166.
	Purpose of review: In this review, we aim to summarize the availability and features of smartphone apps in both the commercial marketplace and academic literature for perinatal depression with the goal of informing patients and clinicians along with giving clinical recommendations related to the integration of mobile apps into perinatal care. Recent findings: There are few apps targeted towards perinatal depression, and of those that exist, most lack evidence and a robust privacy policy. Recent reviews have also highlighted the dearth of quality apps for perinatal mental health care. Summary: Using keywords, searches of the academic literature and Android and Apple App Stores were conducted to identify perinatal depression apps. Notably, there were only six apps included from the app stores, and 18 publications were included from academic literature. Of the commercially available apps, most had concerning privacy policies and contained a paywall to access its features. The academic literature results had small sample sizes and heterogenous outcomes. Additionally, there was a disconnect between the academic apps and those found in app stores; only five of the apps in the academic literature were available commercially yet only one was found in the initial commercial app search. Due to these results, we present a case study of an alternate app, mindLAMP, to illustrate how to incorporate a mobile app into perinatal mental health care. (PsycInfo Database Record (c) 2024 APA, all rights reserved)

Emídio, V.-F., et al. (2021). "Follicular fluid composition and reproductive outcomes of women with polycystic ovary syndrome undergoing in vitro fertilization: a systematic review."
	
Emile Sameh, H., et al. (2019). "Outcome of laparoscopic ventral mesh rectopexy for full-thickness external rectal prolapse: a systematic review, meta-analysis, and meta-regression analysis of the predictors for recurrence." Surgical Endoscopy 33(8): 2444-2455.
	Background: Laparoscopic ventral mesh rectopexy (LVMR) has proved effective in the treatment of internal and external rectal prolapse. The present meta-analysis aimed to determine the predictive factors of recurrence of full-thickness external rectal prolapse after LVMR.; Methods: An organized, systematic search of electronic databases including PubMed/Medline, Embase, Scopus, and Cochran library was conducted in adherence to PRISMA guidelines. Studies that reported the outcome of LVMR in patients with full-thickness external rectal prolapse were included according to predefined criteria. A meta-regression analysis and sub-group meta-analyses were performed to recognize the patient and technical factors that were associated with higher recurrence rates.; Results: Seventeen studies comprising 1242 patients of a median age of 60 years were included. The median operation time was 122.3 min. Conversion to open surgery was required in 22 (1.8%) patients. The weighted mean complication rate across the studies was 12.4% (95% CI 8.4-16.4) and the weighted mean rate of recurrence of full-thickness external rectal prolapse was 2.8% (95% CI 1.4-4.3). The median follow-up duration was 23 months. Male gender (SE = 0.018, p = 0.008) and length of the mesh (SE = - 0.007, p = 0.025) were significantly associated with full-thickness recurrence of rectal prolapse. The weighted mean rates of improvement in fecal incontinence and constipation after LVMR were 79.3% and 71%, respectively.; Conclusion: LVMR is an effective and safe option in treatment of full-thickness external rectal prolapse with low recurrence and complication rates. Male patients and length of the mesh may potentially have a significant impact on recurrence of rectal prolapse after LVMR.

Emily, E.-H., et al. (2021). "Physical activity and/or dietary interventions in infertile women with overweight or obesity prior to infertility treatment - a systematic review and individual participant data meta-analysis (IPDMA)."
	
Emily, W., et al. (2021). "The use of uterine artery embolization (UAE) compared with myomectomy for the management of uterine fibroids: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Emma, S., et al. (2022). "Surgical outcomes of robotic single-site vs. multiport hysterectomy for the treatment of endometrial malignancy: a systematic review and meta-analysis."
	
Emons, G. and C. Gründker (2021). "The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer." Cells 10(2).
	Endometrial cancer (EC) is one of the most common gynecological malignancies. Gonadotropin releasing hormone (GnRH) is a decapeptide first described to be secreted by the hypothalamus to regulate pituitary gonadotropin secretion. In this systematic review, we analyze and summarize the data indicating that most EC express GnRH and its receptor (GnRH-R) as part of an autocrine system regulating proliferation, the cell cycle, and apoptosis. We analyze the available data on the expression and function of GnRH-II, its putative receptor, and its signal transduction. GnRH-I and GnRH-II agonists, and antagonists as well as cytotoxic GnRH-I analogs, have been shown to inhibit proliferation and to induce apoptosis in human EC cell lines in pre-clinical models. Treatment with conventional doses of GnRH-agonists that suppress pituitary gonadotropin secretion and ovarian estrogen production has become part of fertility preserving therapy of early EC or its pre-cancer (atypical endometrial hyperplasia). Conventional doses of GnRH-agonists had marginal activity in advanced or recurrent EC. Higher doses or more potent analogs including GnRH-II antagonists have not yet been used clinically. The cytotoxic GnRH-analog Zoptarelin Doxorubicin has shown encouraging activity in a phase II trial in patients with advanced or recurrent EC, which expressed GnRH-R. In a phase III trial in patients with EC of unknown GnRH-R expression, the cytotoxic GnRH doxorubicin conjugate was not superior to free doxorubicin. Further well-designed clinical trials exploiting the GnRH-system in EC might be useful.

Emons, G., et al. (2021). "Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6)." International Journal of Gynecological Cancer 31(7): 1075‐1079.
	Background The impact of comprehensive pelvic and para‐aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident. Primary Objective Evaluation of the effect of comprehensive pelvic and para‐aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence. Study Hypothesis Comprehensive pelvic and para‐aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65. Trial Design Open label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo‐oophorectomy is performed. In arm B, in addition, a systematic pelvic and para‐aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended. Major Inclusion Criteria Patients with histologically confirmed endometrial cancer stages pT1b‐pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible. Exclusion Criteria Patients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease. Primary Endpoint Overall survival calculated from the date of randomization until death. Sample Size 640 patients will be enrolled in the study. Estimated Dates for Completing Accrual and Presenting Results At present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031. Trial Registration NCT03438474.

Emons, G., et al. (2023). "Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures." Geburtshilfe und Frauenheilkunde 83(8): 919-962.
	Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.; Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of the authors are listed in the long German-language version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet. (© Thieme Medical Publishers.)

Ems (2022). Efficacy and Safety of Different Doses of Venus Association in Patients With Vulvovaginal Candidiasis.
	No Results Available Drug: Venus 20 + 0,064|Drug: Venus 20 + 1|Drug: Venus 20 + 4|Drug: Butoconazole nitrate Time to first relief of symptoms|Adverse events Female Phase 2 0 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment EMS1819 - VENUS March 2024

Energin, H. and H. Eric (2023). "Effect of anterior repair on sexual function in heterosexual couples." International Urogynecology Journal 34(11): 2833-2838.
	Introduction and hypothesis: Little is known about the impact of native tissue repair techniques on heterosexual intercourse. This study was aimed at investigating the effect of anterior colporrhaphy on women's and their partners' sexual function. Method(s): Sexually active women with a male partner who were diagnosed with anterior wall prolapse without any incontinence were prospectively recruited from a single academic center. Demographic data were collected and a Pelvic Organ Prolapse Quantification examination was performed. Before and 3 months post-operatively, women completed two validated questionnaires to assess sexual function, the International Consultation on Incontinence Questionnaire Vaginal Symptoms short form (ICIQ-VS SF) 55, and the Female Sexual Function Index (FSFI), and their male partners completed the International Index of Erectile function-5. Pre- and post-operative results were compared using a paired t test. Result(s): This study was conducted in the gynecology department of a university hospital between May 2022 and June 2023, where 50 heterosexual couples were enrolled and underwent isolated anterior repair. The mean age of women and their partners were 44.3 +/- 5.12 and 48.1 +/- 5.81 respectively. Overall, female sexual function improved significantly from pre- to 3 months postoperatively with a decrease in ICIQ-VS SF scores from 13.3 +/- 3.27 to 1.7 +/- 1.1 (p < 0.05) and an increase in FSFI scores from 21.74 +/- 9.37 to 29.28 +/- 9.97 (p < 0.05). The only domain that did not improve was sexual pain. For their male partners, there was a similar significant improvement in sexual function with an increase in scores from 48.71 +/- 8.71 to 60.68 +/- 8.63 (p < 0.05). Conclusion(s): Isolated anterior repair was associated with improved short-term sexual function amongst heterosexual couples.Copyright © 2023, The International Urogynecological Association.

English, M., et al. (2022). "Fezolinetant for Treatment of Moderate-to-severe Vasomotor Symptoms Associated with Menopause: Results from a 52-week Study (Skylight 2)." Journal of the Endocrine Society 6(Supplement 1): A678-A679.
	Background: SKYLIGHT 2 (NCT04003142) investigated safety and efficacy of fezolinetant (a neurokinin-3 receptor antagonist) on frequency and severity of moderate-to-severe vasomotor symptoms (VMS) and sleep disturbance. In this analysis, persistence of fezolinetant efficacy was investigated over 52 weeks. Method(s): This double-blind Phase 3 study randomized women aged >=40-65 years with moderate-to-severe VMS associated with menopause (average of >=7 hot flashes/day) to once-daily placebo or fezolinetant 30mg or 45mg for 12 weeks. Women completing 12 weeks entered an extension period, with those on placebo re-randomized to fezolinetant 30mg or 45mg (placebo/fezolinetant), and those originally on fezolinetant remaining on their dose for an additional 40-weeks. Fezolinetant efficacy was evaluated vs placebo for 12- weeks through change in VMS frequency, VMS severity, and Patient-reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b (PROMIS) Total Score. Persistence of efficacy for fezolinetant was evaluated descriptively (without statistical comparisons) over the extension period. Result(s): The analysis comprised 484 women (fezolinetant 30mg n=166, fezolinetant 45mg n=167, placebo/fezolinetant 30mg n=76, placebo/fezolinetant 45mg n=75). Improvement in VMS frequency and severity observed through week 12 (statistically significant differences vs placebo) was maintained throughout the 52-week total study period for those receiving fezolinetant. Fezolinetant demonstrated further reductions in VMS frequency and severity from baseline to beyond week 12. For VMS frequency, there was a least squares (LS) mean (SE) baseline-to-week 12 reduction of -6.83 (0.39) VMS/day for fezolinetant 30mg and -7.50 (0.39) for 45mg, and a mean (SD) baseline-to-week 52 reduction of -8.03 (4.53) for fezolinetant 30mg and -8.48 (3.98) for 45mg. For VMS severity, LS mean (SE) baseline-toweek 12 reduction was -0.64 (0.06) for 30mg and -0.77 (0.06) for 45mg, and mean (SD) baseline-to-week 52 reduction was -0.83 (0.82) for fezolinetant 30mg, and - 0.95 (0.78) for 45mg. Women re-randomized from placebo to fezolinetant experienced a reduction in frequency and severity of VMS consistent with that in women receiving fezolinetant throughout the study. Fezolinetant also reduced PROMIS-assessed sleep disturbance, with a LS mean (SE) baseline-to-week 12 reduction of -4.1 (0.5) for fezolinetant 30mg and -5.5 (0.5) for 45mg (statistically significant difference vs placebo for fezolinetant 45mg) and a mean (SD) baseline-to-week 52 reduction of - 6.3 (7.3) for fezolinetant 30mg and -5.7 (7.9) for 45mg. The safety profile observed for the 40-week extension period was consistent with that of the 12-week placebo-controlled period. Conclusion(s): Fezolinetant 30mg and 45mg once daily were efficacious for treatment of moderate-to-severe VMS associated with menopause. Efficacy was persistent and reductions in VMS frequency were maintained during the extension period, at levels consistent with weeks 1 through 12. Fezolinetant 45mg improved sleep at week 12 and improvement was maintained through the active treatment extension period. No safety signals of concern were apparent for either fezolinetant dose.

Engmann, L., et al. (2021). Microfluidics Versus Gradient Centrifugation Effect on Euploidy Rates.
	No Results Available Device: Microfluidics chamber|Other: Density Gradient Centrifugation Euploidy rate of resulting embryos|Pregnancy rates after transfer of euploid embryos Female Not Applicable 150 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 21-106R-1 December 31, 2022

Ensrud Kristine, E., et al. (2022). "Changes in serum endogenous estrogen concentrations are mediators of the effect of low-dose oral estradiol on vasomotor symptoms." Menopause (New York, N.Y.) 29(9): 1014-1020.
	Objectives: The aim of this study was to quantify changes in serum total estradiol (E2) and estrone (E1) concentrations with initiation of low-dose oral estradiol treatment and evaluate whether changes in concentrations mediate the effect of treatment in reducing vasomotor symptom (VMS) frequency.; Methods: We analyzed baseline and week 8 (W8) data from 171 perimenopausal and postmenopausal women with VMS enrolled in low-dose 17β estradiol ( n = 72) and placebo ( n = 99) groups of a randomized clinical trial.; Results: From baseline to W8, women in the low-dose estradiol group had a fourfold increase in E2, resulting in a W8 E2 of 23 pg/mL, and a fivefold increase in E1, resulting in a W8 E1 of 110.7 pg/mL. In contrast, E2 and E1 among women in the placebo group were unchanged from baseline to W8. Changes in E2 and E1 from baseline to W8 met criteria for mediating the effect of low-dose estradiol treatment on VMS frequency. With change in estrogen concentration added to treatment assignment in a regression model predicting W8 VMS frequency, the effect of treatment with low-dose estradiol versus placebo was attenuated, with change in E2 representing a 44.1% reduction ( P = 0.03) and change in E1 representing a 69.5% reduction ( P = 0.02) in total intervention effect.; Conclusion: Among perimenopausal and postmenopausal women with VMS, treatment with low-dose oral estradiol versus placebo results in four- to fivefold increases in serum E2 and E1. The increases in serum E2 and E1 with low-dose oral estradiol treatment seem to mediate in part the effect of treatment in reducing VMS frequency.; Competing Interests: Financial disclosure/conflicts of Interest: S.D.R. reports research funding from Bayer and royalties from UpToDate. S.B. reports his institution has received research grants from MIB, AbbVie, and Transition Therapeutics, on which he is the PI. These grants are unrelated to the work. C.M.M. reports grant support from Merck Inc and consultant and advisory fees from Scynexis and UpToDate. H.J. reports grant support from Merck, Pfizer, NeRRe/KaNDy, and Que Oncology, and consultant and advisory fees from Bayer, Eisai, and Jazz. H.J.'s spouse is an employee of Arsenal Biosciences and has an equity stake in Merck Research Labs and Tango Therapeutics. The other authors declare no conflict of interest. (Copyright © 2022 by The North American Menopause Society.)

Eoh Kyung, J., et al. (2023). "Clinical Relevance of Uterine Manipulation on Oncologic Outcome in Robot-Assisted versus Open Surgery in the Management of Endometrial Cancer." Journal of Clinical Medicine 12(5).
	In this study, we investigated the impact of uterine manipulation on endometrial cancer survival outcomes. We analyzed patients with endometrial cancer who underwent robot-assisted staging and open staging surgery between 2010 and 2020. Either uterine manipulators or vaginal tubes were utilized in robot-assisted staging. Propensity score matching was performed to correct baseline characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curve analysis. In total, 574 patients, including those undergoing robot-assisted staging with a uterine manipulator ( n = 213) or vaginal tube ( n = 147) and staging laparotomy ( n = 214), were analyzed. Propensity score matching was performed for age, histology, and stage as covariates. Before matching, Kaplan-Meier curve analysis showed that PFS and OS were significantly different among the three groups ( p < 0.001 and p = 0.009, respectively). In the propensity-matched cohorts of 147 women, the previously suggested differences in PFS and OS were not observed in patients undergoing robot-assisted staging with a uterine manipulator or vaginal tube or open surgery. In conclusion, robotic surgery using a uterine manipulator or vaginal tube did not compromise survival outcomes in endometrial cancer management.

Epperson, C. N., et al. (2023). "Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program." Journal of Affective Disorders 320: 353-359.
	Background: Brexanolone is currently the only treatment specifically approved for postpartum depression (PPD) in the United States, based on the results from one Phase 2 and two Phase 3 double-blind, randomized, controlled trials in the HUMMINGBIRD program.; Methods: Adults with PPD randomized to a 60-h infusion of brexanolone 90 μg/kg/h (BRX90) or placebo from the 3 trials were included in these post hoc analyses. Data on change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, HAMD-17 Anxiety/Somatization and Insomnia subscales, and Clinical Global Impression of Improvement (CGI-I) scale were pooled. Response rates for HAMD-17 (≥50 % reduction from baseline) and CGI-I (score of 1 or 2) scales and time to response were analyzed.; Results: Patients receiving BRX90 (n = 102) versus placebo (n = 107) achieved a more rapid HAMD-17 response (median, 24 vs 36 h; p = 0.0265), with an Hour-60 cumulative response rate of 81.4 % versus 67.3 %; results were similar for time to CGI-I response (median, 24 vs 36 h; p = 0.0058), with an Hour-60 cumulative response rate of 81.4 % versus 61.7 %. CFB in HAMD-17 Anxiety/Somatization and Insomnia subscales also favored BRX90 versus placebo, starting at Hour 24 through Day 30 (all p < 0.05), and response rates for both subscales were higher with BRX90.; Limitations: The study was not powered to assess exploratory outcomes.; Conclusions: Brexanolone was associated with rapid improvement in depressive symptoms and symptoms of anxiety and insomnia compared with placebo in women with PPD. These data continue to support the use of brexanolone to treat adults with PPD.; Competing Interests: Declaration of competing interest C. Neill Epperson serves on an advisory board for Asarina Pharma and Babyscripts; reports grants awarded to the University of Colorado from Sage Therapeutics, Inc. and HealthRhythms; and receives consulting fees/honoraria from Sage Therapeutics, Inc. David R. Rubinow serves as a consultant and a clinical advisory board co-chair for Sage Therapeutics, Inc.; receives consulting fees and travel/meeting support from Sage Therapeutics, Inc.; and reports grants awarded to University of North Carolina from Sage Therapeutics, Inc. Dr. Rubinow also holds stock options from Sage Therapeutics, Inc. Samantha Meltzer-Brody reports grants awarded to University of North Carolina from Sage Therapeutics, Inc. Dr. Meltzer-Brody also received honoraria from Sage Therapeutics, Inc. Kristina M. Deligiannidis serves as a consultant to Sage Therapeutics, Inc., Brii Biosciences, Inc., and GH Research Ireland Limited, and as a council/board member for Society of Biological Psychiatry and American Society of Clinical Psychopharmacology. Dr. Deligiannidis reports grants awarded to Zucker Hillside Hospital/Feinstein Institutes for Medical Research from Sage Therapeutics, Inc. during the conduct of the brexanolone injection and zuranolone clinical trials. Dr. Deligiannidis also received grants from NIH and Vorso Corporation, royalties from an NIH employee invention outside of the submitted work, payments/honoraria from Platform Q Health Education CME and Peer View Institute for Medical Education, and travel/meeting support from Sage Therapeutics, Inc. and Vorso Corporation. Robert Riesenberg has no conflict of interest to declare. Andrew D. Krystal participates on a data safety monitoring board/advisory board for Idorsia and Neurocrine Biosciences; receives payments/honoraria from Eisai and Idorsia and consulting fees from Adare, Axsome Therapeutics, Big Health, Eisai, Evecxia, Ferring Pharmaceuticals, Galderma, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage Therapeutics, Inc., Takeda, and Angelini; and reports grants from Janssen Pharmaceuticals, Axsome Pharmaceutics, Reveal Biosensors, The Ray and Dagmar Dolby Family Fund, and NIH. Dr. Krystal also holds stock options from Big Health. Kemi Bankole, ng-Yi Huang, Colville Brown, and Robert Lasser are employees of Sage Therapeutics, Inc. and hold stock and/or stock options. Haihong Li and Stephen J. Kanes are former employees of Sage Therapeutics, Inc. and may hold stock and/or stock options. Dr. Kanes is also an inventor of the patent entitled “Neuroactive steroids, compositions, and uses thereof” (US10940156B2), which relates to methods of using brexanolone to treat certain diseases. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Erciyestepe, S. G., et al. (2023). "Can an apparent diffusion coefficient of uterine fibroid before uterine artery embolization predict potential fibroid response?" Ginekologia polska.
	OBJECTIVES: ACOG guidance confirms the use of uterine artery embolisation (UAE) as an alternative to hysterectomy or myomectomy. The main objective of this article is to evaluate the ability of preoperative magnetic resonance imaging (MRI) to study the relationship between uterine fibroid reduction and diffusion coefficient (ADC) value after UAE. This is a relevant topic with the growing interest in using ADC as a noninvasive imaging biomarker for monitoring tissue changes and predicting uterine fibroid response to UAE over the past years. MATERIAL AND METHODS: In this prospective controlled non-randomized trial; uterine fibroid volume, fibroid diameter, uterine volume, fibroid ADC and normal myometrium ADC were recorded before and after UAE. Wilcoxon test was used in the analysis of the dependent quantitative data. Pearson correlation coefficients were calculated between post-UAE uterine volume, fibroid volume, and average fibroid diameter reduction and the patient's age, parity, gravidity, fibroid ADC and myometrial ADC before UAE. RESULT(S): The mean fibroid volume reduction was 36.0% (range between 17.3-77.7%). Mean fibroid diameter, fibroid volume, uterine volume, and myometrium ADC values after UAE were significantly lower than before the procedure (p = 0.002, < 0.001, 0.001, 0.006 respectively), but the decrease in fibroid ADC is not significant. As a result decrease in fibroid volume was greater as pre-UAE fibroid ADC values increased, and that finding may contribute to the selection of the patients for the procedure. CONCLUSION(S): The ADC value before UAE was positively correlated with fibroid volume reduction.

Erdemoğlu, Ç. and D. Aksoy (2022). "The effect of hypnofertility on fertility preparedness, stress, and coping with stress in women having in vitro fertilization: A randomized controlled trial." Journal of Reproductive and Infant Psychology: 1-12.
	BACKGROUND: In vitro fertilisation is a stressful process for women. Hypnofertility is a method that can be used to relieve stress during in vitro fertilisation. It is based on an effective and strong body-mind interaction, as well as balancing the brain and body via positive words and thoughts. OBJECTIVE: This study aimed to investigate the effects of hypnofertility on fertility preparedness, stress, and coping with stress in women undergoing in vitro fertilisation. METHODS: This study was conducted with a randomised controlled trial design. Hypnofertility-based relaxation, visualisation, imagination, and affirmation techniques were applied to the intervention group at four stages, and no initiative was applied to the women in the control group. The Clinical Trial Registration number of the study is NCT04755270. RESULTS: After the hypnofertility method, the mean score of the intervention group in the positive feelings and thoughts subscale of the Fertility Preparedness Scale was higher than that of the control group (p < 0.05). The hypnofertility method caused a significant decrease in the level of infertility stress in the intervention group, and the intervention group used the active-confronting and passive-avoidance methods more than control group did (p < 0.05). CONCLUSION: The hypnofertility method increased the levels of preparedness for fertility, reduced stress levels and provided effective strategies to cope with stress.

Erdogan, O., et al. (2023). "Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study." Asia-Pacific Journal of Clinical Oncology.
	Aim: The aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group. Method(s): Out of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease-free survival (DFS), and disease-specific survival. Result(s): The 5-year DFS of the study cohort was 89%, and the 10-year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS. Conclusion(s): Adjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.Copyright © 2023 John Wiley & Sons Australia, Ltd.

Erekson, E., et al. (2021). "The Design of a Prospective Trial to Evaluate the Role of Preoperative Frailty Assessment in Older Women Undergoing Surgery for the Treatment of Pelvic Organ Prolapse: The FASt Supplemental Trial." Female Pelvic Medicine & Reconstructive Surgery 27(1): e106-e111.
	OBJECTIVE: We present the rationale for and the design of a prospective trial to evaluate the role of preoperative frailty and mobility assessments in older women undergoing surgery for the treatment of pelvic organ prolapse (POP) as a planned prospective supplemental trial to the ASPIRe (Apical Suspension Repair for Vault Prolapse In a Three-Arm Randomized Trial Design) trial. The Frailty ASPIRe Study (FASt) examines the impact of preoperative frailty and mobility on surgical outcomes in older women (≥65 years) participating in the ASPIRe trial. The primary objective of FASt is to determine the impact of preoperative age, multimorbidity, frailty, and decreased mobility on postoperative outcomes in older women (≥65 years old) undergoing surgery for POP. METHODS: The selection of the preoperative assessments, primary outcome measures, and participant inclusion is described. Frailty and mobility measurements will be collected at the preoperative visit and include the 6 Robinson frailty measurements and the Timed Up and Go mobility test. The main outcome measure in the FASt supplemental study will be moderate to severe postoperative adverse events according to the Clavien-Dindo Severity Classification. CONCLUSIONS: This trial will assess impact of preoperative age, multimorbidity, frailty, and decreased mobility on postoperative outcomes in older women (≥65 years old) undergoing surgical procedures for the correction of apical POP. Information from this trial may help both primary care providers and surgeons better advise/inform women on their individual risks of surgical complications and provide more comprehensive postoperative care to women at highest risk of complications.

Erel, C. T. and I. B. Ozcivit (2021). "Re: vaginal Er: YAG LASER application in the menopausal ewe model: a randomised estrogen and sham-controlled trial." BJOG 128(6): 1098.
	
Ergun-Longmire, B. and E. Greydanus Donald (2024). "Ovarian tumors in the pediatric population: An update." Disease-a-month : DM: 101691.
	Research reveals that 1% of neoplasms in females under 17 years of age are ovarian neoplasms and though usually benign, malignant tumors may occur in the pediatric age group. This review considers various current concepts of these tumors including the epidemiology, risk factors, clinical presentations, diagnosis, differential diagnosis, and treatment options including the need to provide fertility-sparing surgery as well as their potential impacts on the psychological well-being of children and adolescents. We gathered data from the published articles ranging from studies, meta-analyses, retrospective studies, and reviews. We focused on the articles published in English between January 1, 2000, and August 31, 2023. Only a few articles published prior to 2000 were included for historical perspective. (Copyright © 2024. Published by Elsevier Inc.)

Erguven, M. and T. Irez (2023). "Hyaluronidase used in oocyte denudation inhibits the proliferation and the viability of cumulus cells through the inhibition of midkine." Human Reproduction 38(Supplement 1): i274.
	Study question: Does hyaluronidase (HAse) have possible negative or positive effects on cumulus cells (CCs) during oocyte denudation before ICSI by altering midkine (MK) levels? Summary answer: Hyaluronidase inhibits the proliferation of CCs via the inhibition of MK activity which may result in poor embryo quality and low ICSI success. What is known already: MK is abundantly expressed in ovarian follicles. MK secreted from the cumulus-granulosa cells that surround oocytes was shown to promote the cytoplasmic maturation of oocytes. This effect of MK could be mediated via its' anti-apoptotic effect and some other mechanisms. The removal of CCs during oocyte denudation (OD) is done in order to select and grade the oocytes before ICSI. HAse is applied for ICSI to break down hyaluronic acid, which is present at high levels in the cumulus-oocyte complex during OD. To date, there have only been a few reported cases of the toxic effects of hyaluronidase on oocytes. Study design, size, duration: This study is a prospective, randomized study done with 90 healthy women between September 2017 and September 2018. Participants/materials, setting, methods: This study was done with women diagnosed as a male factor between the ages of 21 and 40 who underwent ICSI. HAse was applied to the cultured CCs at concentrations of 0.1 IU/ml, 1 IU/ml, and 10 IU/ml. The proliferation and apoptosis indices (Flow cytometry), structures [Transmissive electron microscopy (TEM)], and MK levels (ELISA) of CCs were evaluated every 24 hours for 48 hours. One way-Anova was used and p<0.05 was considered statistically significant. Main results and the role of chance: The application of HAse at all concentrations decreased cumulus cell numbers for 48 hours (p<0.05). The highest decrease in cell number and cell viability with the highest number of apoptotic cells were detected at the 48th hour at the application of the highest concentration of HAse (p<0.05). The highest concentration of HAse application caused the highest decrease in MK levels at the end of 48 hours (p<0.05). Limitations, reasons for caution: The effect of HAse on the CCs of women aged below 21 and above 40 could not be evaluated. Therefore, the overall resistance and fragility of CCs to these HAse concentrations could not be evaluated. In addition, the HAse effects should be evaluated in female infertility cases such as PCOS. Wider implications of the findings: This is the first report to examine the effect of HAse on MK activity. 2-3 lines of CCs are commonly left during oocyte denudation in order to protect the oocyte from stress-induced reactions. The low number of CCs means low MK levels resulting in a loss in oocyte competence.

Erin, R., et al. (2021). "Comparison of Urodynamics Parameters with Intrafascial or Extrafascial Hysterectomy Techniques." Journal of Gynecologic Surgery 37(2): 139‐143.
	Objectives: The aim of this study was to compare urodynamics parameters at pre‐and postoperative periods in patients undergoing intrafascial or extrafascial abdominal hysterectomy. Background: Hysterectomy carries the risk of damage to the pelvic splanchnic nerve, which leads to the development of urinary incontinence. Materials and Methods: Women scheduled for total abdominal hysterectomy were randomized to intrafascial (n = 24) and extrafascial (n = 27). All of the 10 urodynamics parameters investigated in the two techniques at pre‐and postoperative periods were compared. p < 0.05 was chosen to represent the statistical significance for each of the variables. Results: We observed by urodynamics investigation at preoperative and sixth month postoperative periods no urinary incontinence in patients subjected to intrafascial or extrafascial total abdominal hysterectomy. There was no difference between the two techniques with respect to maximum detrussor pressure, maximum abdominal pressure, strong micturition requirement, vesical compliance, detrusor compliance, maximum vesical pressure, first sensation of bladder filling, first desire to void, and strong desire to void (p > 0.05). Maximum bladder capacity in the intrafascial technique was significantly higher than in the extrafascial technique (p < 0.05). Conclusion: No significant relationship was found between the two groups with respect to increase of stress or urge urinary incontinence symptoms and subsequent incontinence after hysterectomy.

Ersahin, S., et al. (2022). "High serum AMH inhibits pathological growth of the low biomass endometrial microbiome." European Review for Medical and Pharmacological Sciences 26(20): 7600-7604.
	Objective: Although host microbiome play a role in both hormonal status and fertility, this issue has not yet been clarified. Since the endometrium is a sterile tissue, it is accepted that microbiota does not grow under normal conditions. The aim of the study was to reveal the characteristics of endometrial microbiota according to serum AMH levels in women with implantation failure.; Patients and Methods: Forty-five women aged 20-30 years with two or more implantation failures were included in the study. They were divided into 3 groups according to their serum AMH values: Group 1 -AMH <1.3 ng/ml; Group 2 - AMH between 1.3-2.6 ng/ml; Group 3 - AMH >2.6 ng/ml. Twenty-two healthy fertile women who were the same age as the infertile group and applied for cervical smear screening were accepted as the control group. Following the embryo transfer, the tip of the catheter was inserted into the transport medium under sterile conditions. Sowing was carried out by touching the tips of the catheter to the blood agar medium. After the evaluation of the petri dishes at the end of 48 hours of incubation, colonies were stained with Gram stain. Microorganisms in the colonies were identified with the Vitek-2 device according to their gram-staining characteristics and their antibiograms were made.; Results: A negative correlation was detected between low AMH values and the microbiome detection rates in endometrial cultures. In patients with low serum AMH levels, the chance of endometrial microbiota growth was higher in the endometrial culture medium. The most common bacteria were found to be MSSA, MRKNS and lactobacillus. Clinical pregnancy rates were found to be significantly higher in the group with high AMH levels. As AMH levels increased, positive flora detection rates decreased, while clinical pregnancy rates increased.; Conclusions: Low serum AMH level increases the rate of positive endometrial microbiome in culture and decreases clinical pregnancy rates.

Erzincan, M. and Hospital (2021). "The Effect of Hot Pack Application on Postoperative Ileus Undergoing Surgery for Gynecologic Malignancies." ClinicalTrials.gov.
	Postoperative ileus (POI), is an extensively known complication characterized by an impairment of normal gastrointestinal motor activity after abdominal surgery and may also occur after surgery at other sites due to non‐mechanical causes. [1]. This clinical asset has been linked to prominent perioperative morbidity with the following financial burden owing to extended hospitalization [1]. Furthermore, POI can postpone adjuvant treatments, such as chemotherapy in patients who went through surgery for cancers. Abdominal tenderness and distension, nausea and vomiting, delay in the passage of flatus and stool, and intolerance to solid food are the prime symptoms of POI [1‐3]. It is generally transient, but if prolonged, can cause surgical incision dehiscence, intestinal anastomotic fistula, abdominal cavity infection, intestinal ischemia, aspiration pneumonia, and other serious complications [4‐6]. Hence, many clinicians have focused on averting POI. Many studies have analyzed preventive methods, such as preoperative mobilization of the patient, adequate pain control, gum chewing, epidural anesthesia, coffee consumption, and motility agents such as metoclopramide and alvimopan [7‐15]. For all the manifold remedy approaches, POI maintains a difficult clinical challenge that compromises the rapid improvement of patients who underwent abdominal surgery. Recently, thermal attempts have been employs for several situations such as inflammatory bowel disease, chronic pelvic pain, and abdominal pain [16]. It may be used in two different ways; whole body or local. Local thermal therapy can be carried out by hot pack or paraffin [17]. It has been demonstrated that local thermotherapy abate myotonia, enhances circulation, and eases pain by expediting the removal of the pain‐producing substance. Local thermal therapy is widely used for a number of conditions such as pain, nausea, vomiting, and some bowel diseases in traditional Chinese medicine [18]. Only one study has shown that hot pack therapy at the postoperative period has a positive effect on bowel motility. However, this study has a lot of weaknesses. Moreover, until now, no study has specifically investigated the effect of the hot pack on gynecological oncology surgery. The investigators hypothesized that using a hot pack during the early postoperative period would accelerate the return of gastrointestinal motility. Therefore, investigators performed a randomized controlled trial (RCT) to assess whether using hot pack whips up the recovery of gut function after gynecological oncology surgery

Escarcega-Bordagaray, J. A., et al. (2024). "Basal characteristics of patients who responded to Ovarian Fragmentation for Follicular Activation (OFFA) or In Vitro Activation (IVA): a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics.
	A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.

Eskander Ramez, N. (2024). "Revisiting immunotherapy in endometrial cancer." Clinical advances in hematology & oncology : H&O 22(1): 28-30.
	
Eskander Ramez, N., et al. (2023). "Overcoming the challenges of drug development in platinum-resistant ovarian cancer." Frontiers in Oncology 13: 1258228.
	The definition of "platinum-resistant ovarian cancer" has evolved; it now also reflects cancers for which platinum treatment is no longer an option. Standard of care for platinum-resistant ovarian cancer is single-agent, non-platinum chemotherapy with or without bevacizumab, which produces modest response rates, with the greatest benefits achieved using weekly paclitaxel. Several recent phase 3 trials of pretreated patients with prior bevacizumab exposure failed to meet their primary efficacy endpoints, highlighting the challenge in improving clinical outcomes among these patients. Combination treatment with antiangiogenics has improved outcomes, whereas combination strategies with immune checkpoint inhibitors have yielded modest results. Despite extensive translational research, there has been a lack of reliable and established biomarkers that predict treatment response in platinum-resistant ovarian cancer. Additionally, in the platinum-resistant setting, implications for the time between the penultimate dose of platinum therapy and platinum retreatment remain an area of debate. Addressing the unmet need for an effective treatment in the platinum-resistant setting requires thoughtful clinical trial design based on a growing understanding of the disease. Recent cancer drug approvals highlight the value of incorporating molecular phenotypes to better define patients who are more likely to respond to novel therapies. Clinical trials designed per the Gynecologic Cancer InterGroup recommendations-which advocate against relying solely upon the platinum-free interval-will help advance our understanding of recurrent ovarian cancer response where platinum rechallenge in the platinum-resistant setting may be considered. The inclusion of biomarkers in clinical trials will improve patient stratification and potentially demonstrate correlations with biomarker expression and duration of response. With the efficacy of antibody-drug conjugates shown for the treatment of some solid and hematologic cancers, current trials are evaluating the use of various novel conjugates in the setting of platinum-resistant ovarian cancer. Emerging novel treatments coupled with combination trials and biomarker explorations offer encouraging results for potential strategies to improve response rates and prolong progression-free survival in this population with high unmet need. This review outlines existing data from contemporary clinical trials of patients with platinum-resistant ovarian cancer and suggests historical synthetic benchmarks for non-randomized trials.; Competing Interests: RE reports receiving institution research support from AstraZeneca, Clovis Oncology, Eisai, Merck, and Novocure; and consulting and advisory fees from AstraZeneca; Cardiff Oncology; Clovis Oncology; Eisai; Elevar; Genentech/Roche; GSK/Tesaro; ImmunoGen, Inc; Merck; Mersana; and Myriad. KM reports advisory board participation for Addi; Alkermes; Aravive, Inc; AstraZeneca; Blueprint Pharma; Caris; Celsion Corporation; Clovis; Eisai Co, Ltd; Eli Lilly and Company; EMD Serono; Genentech, Inc/Roche; GlaxoSmithKline plc/Tesaro; I-MAB Biopharma Co, Ltd; ImmunoGen, Inc; InxMed Co, Ltd; Jiangsu Hengrui Pharmaceuticals Company Ltd; Merck & Co, Inc; Mereo Biopharma Group plc; Mersana Therapeutics, Inc; Myriad Genetics, Inc; Novartis Pharmaceuticals Corporation; Novocure GmbH; Onconova Therapeutics, Inc; OncXerna Therapeutics, Inc; Tarveda Therapeutics; VBL Therapeutics; and Verastem, Inc; research funding from Eli Lilly and Company; GlaxoSmithKline plc/Tesaro; Merck & Co, Inc; PTC Therapeutics; and Verastem, Inc; and employment by GOG Partners, NRG Ovarian Cancer Committee Chair, and employment by The GOG Foundation Inc uncompensated. BM reports receiving speaker and/or consultant fees from Acrivon; Adaptimmune; Amgen; Aravive; AstraZeneca; Bayer; Clovis; Eisai; Elevar; Genmab/Seagen; the GOG Foundation; Gradalis; Heng Rui; ImmunoGen, Inc; Laekna; MacroGenics; Merck; Mersana; Myriad; Novartis; Novocure; OncoC4; Panavance; Pieris; Pfizer; Roche/Genentech; Sorrento; TESARO/GSK; L; Verastem; and Zentalis; and consultant and/or investigator fees from US Oncology Research. TH reports advisory board participation for AstraZeneca; Caris; Clovis; Eisai Co, Ltd; Epsilogen Ltd; Genentech, Inc; GlaxoSmithKline plc; Johnson & Johnson; Merck & Co, Inc; Mersana Therapeutics, Inc; and Seagen Inc. CA reports nothing to disclose. DO reports receiving institutional funds from AbbVie; Advaxis; Agenus, Inc; Alkermes; Aravive, Inc; Arcus Biosciences, Inc; AstraZeneca; BeiGene USA, Inc; Boston Biomedical; Bristol Myers Squibb; Clovis Oncology; Deciphera Pharma; Eisai; EMD Serono, Inc; Exelixis; Genentech, Inc; Genmab; GlaxoSmithKline; GOG Foundation; Hoffmann-La Roche, Inc; ImmunoGen, Inc; Incyte Corporation; IOVANCE Biotherapeutics; Karyopharm; Leap Therapeutics, Inc; Ludwig Institute for Ca; Merck & Co, Inc; Merck Sharp & Dohme Corp; Mersana Therapeutics, Inc; NCI; Novartis; Novocure; NRG Oncology; OncoC4, Inc; OncoQuest, Inc; Pfizer, Inc; Precision Therapeutics, Inc; Prelude Therapeutics; Regeneron Pharmaceuticals, Inc; RTOG; Rubius Therapeutics; Seattle Genetics Seagen; Sutro Biopharma; SWOG; TESARO; and Verastem, Inc; and consultant and/or advisory board personal fees from AbbVie; Adaptimmune; Agenus, Inc; Arquer Diagnostics; Arcus Biosciences, Inc; AstraZeneca; Atossa Therapeutics; Boston Biomedical; Cardiff Oncology; Celcuity; Clovis Oncology; Corcept Therapeutics; Duality Bio; Eisai; Elevar; Exelixis; Genentech, Inc; Genelux; GlaxoSmithKline; GOG Foundation; Hoffmann-La Roche, Inc; ImmunoGen, Inc; Imvax; InterVenn; INXMED; IOVANCE Biotherapeutics; Janssen; Jazz Pharmaceuticals; Laekna; Leap Therapeutics, Inc; Luzsana Biotechnology; Merck & Co, Inc; Merck Sharp & Dohme Corp; Mersana Therapeutics, Inc; Myriad; Novartis; Novocure; OncoC4, Inc; Onconova; Regeneron Pharmaceuticals, Inc; Replimmune; R-PHARM US, LLC; Roche Diagnostics; Seattle Genetics Seagen; Sorrento; Sutro Biopharma; Tarveda Therapeutics; Toray; Trillium; Umoja; Verastem, Inc; VBL Therapeutics; Vincerx Pharma; Xencor; and Zentalis. RC reports research funding from AbbVie Inc; AstraZeneca; Clovis; Genmab A/S; ImmunoGen, Inc; Merck & Co, Inc; Mersana Therapeutics, Inc; Roche/Genentech, Inc; and Toray; and scientific steering committee participation with AbbVie Inc; Agenus Inc; Aravive, Inc; AstraZeneca; Clovis; Deciphera Pharmaceuticals, Inc; Epsilogen Ltd; Genentech, Inc; Genmab A/S/Seagen Inc; GlaxoSmithKline plc; ImmunoGen, Inc; Karyopharm Therapeutics Inc; Merck & Co, Inc; Mirati Therapeutics, Inc; Novocure GmbH; OncXerna Therapeutics, Inc; and Toray. (Copyright © 2023 Eskander, Moore, Monk, Herzog, Annunziata, O’Malley and Coleman.)

Eskew Ashley, M., et al. (2019). "Letrozole Compared With Clomiphene Citrate for Unexplained Infertility: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 133(3): 437-444.
	Objective: To estimate the clinical effectiveness, as determined by positive pregnancy test, of letrozole compared with clomiphene citrate for ovarian stimulation in patients with unexplained infertility.; Data Sources: We conducted a systematic review and meta-analysis of data from electronic databases including Ovid-MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and ClinicalTrials.gov.; Methods: We searched for concepts of unexplained infertility, letrozole, clomiphene citrate, and clinical outcomes including pregnancy and live birth. Studies were included if they were randomized controlled trials (RCTs) comparing clomiphene citrate with letrozole in patients with unexplained infertility. Eight RCTs including 2,647 patients with unexplained infertility were included. Primary outcome was positive pregnancy test per patient. Secondary outcomes included positive pregnancy test per cycle, clinical pregnancy, live birth, spontaneous miscarriage, twin gestation, mean serum estradiol (E2), endometrial thickness, and number of dominant follicles. The Cochrane Q test and Higgin's I were used to assess heterogeneity. Random effects models were used to obtain pooled relative risks (RR) and 95% CIs.; Tabulation, Integration, and Results: In analysis per patient, there was no significant difference in positive pregnancy test between patients treated with letrozole compared with clomiphene citrate (24% vs 23%, pooled RR 1.08, 95% CI 0.85-1.36). Significant heterogeneity was noted between studies (I=60.8%). There were no significant differences in clinical pregnancy (pooled RR 1.15, 95% CI 0.71-1.85), live birth (pooled RR 0.94, 95% CI 0.83-1.08), spontaneous miscarriage (pooled RR 0.92, 95% CI 0.61-1.38), or twin gestation (pooled RR 0.81, 95% CI 0.39-1.68). Mean serum E2 was significantly lower in the letrozole group than in the clomiphene citrate group.; Conclusion: Although limited by heterogeneity, studies of ovarian stimulation in women with unexplained infertility show no difference in clinical outcomes between letrozole and clomiphene citrate.

Esmaeilian, Y., et al. (2023). "IVF characteristics and the molecular luteal features of random start IVF cycles are not different from conventional cycles in cancer patients." Human reproduction (Oxford, England) 38(1): 113-124.
	Study Question: Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional cycles in cancer patients?; Summary Answer: No; controlled ovarian stimulation cycles randomly started at late follicular phase (LFP) and luteal phase (LP) are totally comparable to those conventional IVF cycles started at early follicular phase (EFP) in terms of the expression of the enzymes involved in cholesterol utilization and steroid hormone biosynthesis pathways, gonadotropin receptor expression and, estradiol (E2) and progesterone (P4) production in addition to the similarities in ovarian response to gonadotropin stimulation, oocyte yield, fertilization rate and embryo development competency in cancer patients.; What Is Known Already: Random start ovarian stimulation protocols are commonly employed for oocyte and embryo freezing for fertility preservation in cancer patients with time constraints who do not have sufficient time to undergo ovarian stimulation initiated conventionally at EFP of the next cycle. No data is available regarding the molecular steroidogenic features of these cycles analyzed together with the clinical IVF characteristics in cancer patients. We aimed to address this question in this study to help understand how similar the random start cycles are to the conventional start ones.; Study Design, Size, Duration: A clinical translational research study conducted in 62 cancer patients undergoing IVF for fertility preservation between the years 2017 and 2022.; Participants/materials, Setting, Methods: Sixty-two patients who were diagnosed with different types of cancer and underwent ovarian stimulation for oocyte (n = 41) and embryo (n = 21) cryopreservation using GnRH antagonist protocol and human menopausal gonadotropins before receiving cancer treatment/surgery were enrolled in the study. For patients with breast cancer and endometrial cancer the aromatase inhibitor letrozole was used with gonadotropin stimulation. Ovarian stimulation was initiated conventionally at EFP in 22 patients and served as control while it was started at LFP in 20, and mid-LP in the other 20 patients. The luteinized granulosa cells (GCs) were recovered from follicular aspirates during oocyte retrieval procedure and used for the experiments separately for each individual patient. The expression of the enzymes involved in sex steroid biosynthesis (StAR, 3β-HSD, Aromatase) and cholesterol synthesis (3-hydroxy 3-methylglutaryl Co-A reductase (HMG-Co-A reductase)), utilization (hormone sensitive lipase (HSL)), and storage (Acetyl-Coenzyme A acetyltransferase 1 (ACAT-1)), and gonadotropin receptor expression status were analyzed using immunoblotting and RT-PCR methods. Laser confocal immunofluorescence imaging was applied to analyze and compare the expression patterns of the steroidogenic enzymes and their relation with mitochondria. In vitro E2 and P4 production by the cells were compared among the groups.; Main Results and the Role of Chance: Baseline demographic and IVF characteristics of the patients undergoing the conventional start and random start IVF cycles were similar. Duration of gonadotropin stimulation was significantly longer in LFP and LP start cycles in comparison to the conventional ones. Ovarian response to gonadotropin stimulation, mature and total oocyte yield, fertilization and Day 5 blastulation rates of the embryos were comparable between the conventional versus random start cycles. When the luteal GCs of these random start cycles were analyzed we could not find any gross differences between these cycles in terms of the viability index and gross light microscopic morphologic features. More detailed analysis of the molecular luteal characteristics of the cells using RT-PCR, immunoblotting methods revealed that the expression profiles of the gonadotropin receptors, and the enzymes involved in sex steroid biosynthesis and cholesterol synthesis/utilization, and the steroidogenic activity of the luteal GCs of the random start cycles are almost identical to those of the conventional start cycles. Confocal image analysis demonstrated similar patterns in the signal expression profiles of the steroidogenic enzymes and their co-localization within mitochondria.; Large Scale Data: N/A.; Limitations, Reasons for Caution: Caution should be exercised when interpreting our data and counseling cancer patients seeking fertility preservation because it is still unclear if previous exposure to cancer drugs, different ovarian pathologies or infertility etiologies, previous ovarian surgery and/or any other underlying diseases that are concomitantly present with cancer may cause a difference between conventional and random start stimulation protocols in terms of IVF parameters, luteal function and reproductive outcome. Relatively low number of patients in each stimulation protocol and pooling of luteal GCs for each patient rather than individual analysis of each follicle and oocyte are additional limitations of our study.; Wider Implications of the Findings: Our findings provide reassurance that random start protocol offers cancer patients an equally good prospect of fertility preservation as conventional IVF.; Study Funding/competing Interest(s): Funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest.; Trial Registration Number: N/A. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Espitalier, F., et al. (2021). ""Impact of Nociception Level (NOL) index intraoperative guidance of fentanyl administration on opioid consumption, postoperative pain scores and recovery in patients undergoing gynecological laparoscopic surgery. A randomized controlled trial"." Journal of Clinical Anesthesia 75: 110497.
	Study objective: The Nociception Level (NOL) index uses a multiparametric approach to measure the balance between sympathetic and parasympathetic systems activity. Recently, a strong correlation between the NOL index response to nociceptive stimuli and the level of opioid analgesia during surgery was reported. Others observed that intraoperative doses of remifentanil and sufentanil were reduced when the NOL index was used. So far, no study has evaluated the impact of NOL‐guided fentanyl antinociception in laparoscopic gynecological surgery. The primary hypothesis of this present study was to evaluate whether intraoperative NOL‐guided fentanyl administration would reduce intra‐operative opioid consumption. Secondary hypotheses were to assess whether this would lead to lower postoperative opioid consumption and pain scores, as well as improved postoperative outcomes. Setting: University hospital, operating room. Patients: 70 adult patients, ASA 1–3, scheduled for total laparoscopic hysterectomy. Interventions: Patients were randomized into 2 groups: SOC (standardization of care) and NOL (using the NOL index to guide the administration of fentanyl). The depth of anesthesia was monitored with BIS™. Intraoperative fentanyl boluses were administered based on heart rate and mean arterial pressure variations in the SOC group, and NOL index for the NOL group. Measurements: Fentanyl total intraoperative dose administered was collected and also averaged per hour. Pain scores and hydromorphone consumption were assessed in the post‐anesthesia care unit and up to 24 h. Main results: Sixty‐six patients completed the study, 33 in each group. Total intraoperative fentanyl administration was not different between the two groups (217 (70) in the NOL group vs 280 (210) in the SOC group (P = 0.11)). Nevertheless, intraoperative fentanyl administration per hour was reduced by 25% in the NOL‐guided group compared to the SOC group: 81 (24) vs 108 (66) μg.h−1, respectively (P = 0.03). Hydromorphone consumption and pain scores in the post‐anesthesia care unit and at 24 h were not significantly different between the two groups. Conclusion: NOL‐guided analgesia allowed for a 22% reduction of the total amount of intraoperative fentanyl which was not significant. Nevertheless, results reported a significant reduction by 25% in the doses of fentanyl averaged per hour of surgery and administered in the NOL‐guided group compared with the standardized practice in laparoscopic gynecological surgery. The pain measured postoperatively was similar in the two groups while the average postoperative consumption of opioids to achieve the same level of pain scores in post‐anesthesia care unit and at 24 h was not significantly reduced. Further larger multicenter studies centered towards postoperative outcomes are needed.

Estevez, S. L., et al. (2022). "OBSTETRIC OUTCOMES OF FERTILITY PATIENTS WITH PELVIC PAIN DISORDERS." Fertility and Sterility 118(4 Supplement): e95-e96.
	Objective: Previous research has shown vaginismus to be an independent risk factor for cesarean delivery (CD).1 CD is associated with increased maternal and neonatal morbidity compared with vaginal deliveries; despite this, the rate of CD continues to rise. The American College of Obstetricians and Gynecologists has proposed strategies to help reduce the rate of CD. Most of which focus on the peripartum and intrapartum periods. Therefore, an opportunity exists for reproductive endocrinology and infertility (REI) providers to identify patients at risk for CD based on a history of pelvic pain disorders (PPDs). Material(s) and Method(s): The study included all nulliparous patients undergoing assisted reproductive technology (ART) treatment at a single academic fertility center who had a live birth from 2012-2020. Cases included all patients diagnosed with PPDs. A 3:1 ratio propensity score matched population of patients without PPDs was included as a control group. Patients were matched by age, body mass index (BMI), and anti-Mullerian hormone (AMH). Baseline demographics were collected and included age, BMI, marital status, duration of infertility, AMH, history of anxiety disorders, use of anxiolytics, and obstetrical outcomes. Exclusion criteria were pregnancy outside of treatment, fibroids, Mullerian anomalies, and prior uterine surgery. Comparative statistics were performed using chi-square and students t-test where appropriate. A multivariate regression analysis was conducted to evaluate the association between PPDs and mode of delivery. A total sample size of 170 patients per group was calculated in order to detect a 15% difference is CD rates with an 80% power (alpha=0.05). Result(s): 174 patients who reported a history of a PPD were compared to 575 controls. Demographic characteristics were comparable among groups. Significant differences were found in the duration of infertility among groups with PPD patients reporting a longer duration of infertility (18.9+/-20 vs 14.0+/-14 vs. p=0.003). Patients in the PPD group had significantly higher diagnosis of anxiety disorders (115+/-21.9 vs. 55+/-31.6, p< 0.009) and use of anxiolytics (17+/-3.2 vs. 12+/-6.9, p< 0.03) as compared to controls. The prevalence of chronic hypertension was significantly higher in patients with PPDs (6+/-3.4 vs 5+/-1 p<0.02). Patients with a history of PPD had a higher rate of CD compared with controls (59.8% vs. 49.2% p=0.01). Additionally, after adjusting for age, BMI, AMH, duration of infertility, and fertility diagnosis, there was a significant association between having a diagnosis of PPD and increased odds of having a CD (aOR= 1.5, CI 95%; 1.06-2.20). Conclusion(s): Patients with PPDs have significantly greater odds of CD, higher rates of anxiety disorders, and increased use of anxiolytics compared to patients without a history of pelvic pain. Impact Statement: REIs could serve as a point of intervention and referral for patients with PPDs. Pelvic physical therapy, emotional support, and insertion training may be beneficial in improving patient experience and outcomes, and reducing the risk of CD. Support: None REFERENCES:: 1. Moller L, Josefsson A, Bladh M, Lilliecreutz C, Sydsjo G. Reproduction and mode of delivery in women with vaginismus or localised provoked vestibulodynia: a Swedish register-based study. BJOG. 2015 Feb;122(3):329-34. Epub 2014 Jul 3. PMID:.Copyright © 2022

Ethier, J.-L., et al. (2022). "State of the Biomarker Science in Ovarian Cancer: A National Cancer Institute Clinical Trials Planning Meeting Report." JCO precision oncology 6: e2200355.
	Purpose: Despite therapeutic advances in the treatment of ovarian cancer (OC), 5-year survival remains low, and patients eventually die from recurrent, chemotherapy-resistant disease. The National Cancer Gynecologic Cancer Steering Committee identified the integration of scientifically defined subgroups as a top strategic priority in clinical trial planning.; Methods: A group of experts was convened to review the scientific literature in OC to identify validated predictive biomarkers that could inform patient selection and treatment stratification. Here, we report on these findings and their potential for use in future clinical trial design on the basis of hierarchal evidence grading.; Results: The biomarkers were classified on the basis of mechanistic targeting, including DNA repair and replication stress, immunotherapy and tumor microenvironment, oncogenic signaling, and angiogenesis. Currently, BRCA mutations and homologous recombination deficiency to predict poly (ADP-ribose) polymerase inhibitor response are supported in OC by the highest level of evidence. Additional biomarkers of response to agents targeting the pathways above have been identified but require prospective validation.; Conclusion: Although a number of biomarkers of response to various agents in OC have been described in the literature, high-level evidence for the majority is lacking. This report highlights the unmet need for identification and validation of predictive biomarkers to guide therapy and future trial design in OC.

Etrusco, A., et al. (2024). "Efficacy, safety, and feasibility of the treatment of intrauterine pathologies with the mini-resectoscope: A systematic review." International Journal of Gynecology and Obstetrics.
	Background: Hysteroscopy represents the gold standard for the diagnosis and treatment of intrauterine pathologies. The advent of the mini-resectoscope heralded a new era in intrauterine surgery, both in inpatient and outpatient settings. Objective(s): To evaluate the effectiveness, safety, and feasibility of the mini-resectoscope for the treatment of intrauterine pathologies. Search Strategy: Electronic databases were searched for English-language trials describing surgical procedures for uterine pathologies performed with a mini-resectoscope until 30 April 2023. Selection Criteria: Retrospective or prospective original studies reporting the treatment of uterine pathologies with mini-resectoscope were deemed eligible for the inclusion. Data Collection and Analysis: Data about study features, characteristics of included populations, surgical procedures, complications, and results/outcomes were collected. Result(s): Seven papers that met the inclusion criteria were included in this systematic review. Quantitative analysis was not possible due to data heterogeneity. A descriptive synthesis of the results was provided accordingly to the pathology hysteroscopically removed/corrected: polyps and myomas, uterine septum, intrauterine synechiae, and isthmocele. Conclusion(s): The mini-resectoscope is poised to play a leading role in hysteroscopic surgery for many pathologies, both in inpatient and outpatient settings. Since some applications of the mini-resectoscope have not yet been thoroughly investigated, future studies should address current knowledge gaps, designing high-quality comparative trials on specific applications.Copyright © 2024 International Federation of Gynecology and Obstetrics.

Eubanks, A. (2023). "Hormone Therapy: Menopausal Hormone Therapy." FP essentials 531: 15-21.
	The marked decrease in estrogen levels in menopausal women can cause bothersome symptoms that affect daily life. More than 75% of women experience menopausal symptoms, which can include vaginal dryness, itching, discharge, dyspareunia, mood changes, hot flushes, and night sweats. Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms. Benefits include decreased risk of osteoporotic fractures and vaginal atrophy, improved glycemic control, and decreased vasomotor symptoms. However, recent research on risks associated with MHT has shown increased risk of venous thromboembolism and breast cancer. MHT typically is an option for patients younger than 60 years or within 10 years of menopause onset with bothersome vasomotor symptoms. The decision to start MHT should be made on an individual basis after a thorough evaluation and counseling. Oral, intramuscular, transdermal, and intravaginal formulations are available. The goal of therapy is use of the lowest dose for the shortest time that effectively manages symptoms. The patient and physician should regularly assess the risks and benefits associated with MHT and ensure that the benefits of its use continue to outweigh the risks. (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Euctr, A. T. (2021). "The trial assesses the efficacy and safety of a vaginalgel for dryness." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: Estrokad 0.03 Vaginalzäpfchen Product Name: Estrokad 0.03mg Vaginalzäpfchen Pharmaceutical Form: Suppository INN or Proposed INN: ESTRIOL CAS Number: 50‐27‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.03‐ CONDITION: ; MedDRA version: 21.1 Level: LLT Classification code 10047782 Term: Vulvovaginal atrophy System Organ Class: 100000004872 Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] PRIMARY OUTCOME: Main Objective: To assess the efficacy of the investigational medical device on vaginal dryness symptoms in adult subjects; To assess the safety of the investigational medical device in adult subjects; Primary end point(s): Efficacy:; Improvement in vaginal dryness estimated with the VAS ; Safety:; Amount of adverse events occurred since baseline estimated via reports and interviews ; Amount of serious adverse events occurred since baseline estimated via reports and interviews ; Secondary Objective: To assess user’s experience with the product under investigation (usability, customer satisfaction, package information leaflet / instruction for use) Timepoint(s) of evaluation of this end point: Week 3 SECONDARY OUTCOME: Secondary end point(s): Efficacy:; Improvement in vaginal dryness estimated with the VAS ; Improvement in vaginal burning estimated with the VAS ; Improvement in vaginal itching estimated with the VAS ; Satisfaction with the treatment method estimated with a questionnaire ; Timepoint(s) of evaluation of this end point: Week 3 and week 12 INCLUSION CRITERIA: • Informed consent • Biological sex: female (women only) • Women with moderate or severe vaginal dryness • Age > 18 years Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range

Euctr, B. E. (2021). "Study to Evaluate the Efficacy and Safety of Miconazole Nitrate 2% + Domiphen Bromide Vaginal cream in the Treatment of Subjects with Acute Vulvovaginal Candidiasis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Miconazole Nitrate Pharmaceutical Form: Vaginal cream INN or Proposed INN: DOMIPHEN BROMIDE CAS Number: 538‐71‐6 Concentration unit: % (W/W) percent weight/weight Concentration type: equal Concentration number: 0.14‐ Trade Name: Gyno‐Daktarin Pharmaceutical Form: Vaginal cream Product Name: Miconazole Nitrate Pharmaceutical Form: Vaginal cream INN or Proposed INN: DOMIPHEN BROMIDE CAS Number: 538‐71‐6 Concentration unit: % (W/W) percent weight/weight Concentration type: equal Concentration number: 0.29‐ CONDITION: acute vulvovaginal candidiasis Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: The primary objectives of this study are to evaluate the efficacy of vaginal miconazole nitrate 2% + domiphen bromide cream in the treatment of VVC compared to miconazole nitrate 2% based on the cure rate of VVC at Day 15, and to determine the most optimal dose of domiphen bromide (0.14% or 0.29%) for the treatment of VVC through Week 12.; Primary end point(s): Primary efficacy endpoints :; •The proportion of subjects with clinical cure at the first follow‐up visit (Day 15); •The proportion of subjects with mycological eradication at the first follow‐up visit (Day 15); •The proportion of subjects with overall therapeutic success at the first follow‐up visit (Day 15); Secondary Objective: The secondary objectives of this study are to:; •Evaluate the safety and tolerability of the two formulations of vaginal miconazole nitrate + domiphen bromide cream through Week 12.; •Evaluate the efficacy of vaginal miconazole nitrate + domiphen bromide cream in the treatment of VVC compared to miconazole nitrate 2% based on the cure rate of VVC at Day 29, Day 57 and Day 85.; •Evaluate the efficacy of the two formulations of vaginal miconazole nitrate + domiphen bromide treatment on patient reported outcomes through Week 12. ; Timepoint(s) of evaluation of this end point: Day 15 SECONDARY OUTCOME: Secondary end point(s): Secondary efficacy endpoints :; • The proportion of subjects with clinical cure at the first follow‐up visit through Week 12.; • The proportion of subjects with mycological eradication at the first follow‐up visit through Week 12.; • The proportion of subjects with overall therapeutic success (defined as clinical cure and mycological eradication) through Week 12.; • Change from Baseline through Week 12 in vulvovaginitis symptom questionnaire total score.; • Change from Baseline through Week 12 in the EQ‐5D questionnaire total score.; Secondary safety endpoints :; • Change from Baseline in clinical laboratory parameters on Follow‐Up Visits; (Serum chemistry, hematology and urinalysis through Week 12); • Frequency and severity of Adverse Events during treatment period as well as post‐treatment (AEs); • Change from Baseline in vital signs on Follow‐Up Visits through Week 12 Timepoint(s) of evaluation of this end point: through Week 12, including follow‐up visits on Day 15, Day 29, Day 57 and Day 85 INCLUSION CRITERIA: Subjects must be generally healthy, non‐pregnant females 18‐50 years of age at Screening Visit. Subjects must have an acute VVC episode at Screening Visit, defined as a total signs and symptoms score of =3 and a positive KOH wet mount preparation or Gram stain from a vaginal smear revealing filamentous hyphae/pseudohyphae and/or budding yeast cells. Subjects of childbearing potential must have a negative pregnancy test before randomization and may not be lactating or planning to become pregnant during the study period. Subjects of childbearing potential must agree to use highly effective methods of contraception or to abstain from sexual intercourse. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 95 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Euctr, D. E. (2021). "A PHASE 2b, OPEN-LABEL STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF VACCINE CANDIDATE BNT162b2 IN IMMUNOCOMPROMISED PARTICIPANTS =2 YEARS OF AGE." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: COMIRNATY Product Name: BNT162b2 Product Code: RBP020.2 (PF‐07302048) Pharmaceutical Form: Concentrate for solution for injection INN or Proposed INN: NAP Current Sponsor code: BNT162b2 Other descriptive name: Tozinameran Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 500‐ CONDITION: Protection against COVID‐19 ; MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] SECONDARY OUTCOME: Secondary end point(s): Not Applicable Timepoint(s) of evaluation of this end point: Not Applicable INCLUSION CRITERIA: Participants are eligible to be included in the study only if all of the following criteria apply: Age and Sex: 1.Male or female participants who are =2 years of age at the time of enrollment (Visit 1). 2.Participants or participants’ parent(s)/legal guardians, as age appropriate, who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 3.Life expectancy =12 months (365 days) in the opinion of the investigator at enrollment (Visit 1). 4.Participants or participant’s parent(s)/legal guardians, as age appropriate, who are able to be contacted by telephone throughout the study period. 5.Female participant of childbearing potential or male participant able to father children who is willing to use a highly effective method of contraception as outlined in this protocol for at least 28 days after the last dose of study intervention if at risk of pregnan PRIMARY OUTCOME: Main Objective: To describe the immune response to prophylactic BNT162b2 in participants =18 years of age without serological or virological evidence of past SARS‐CoV‐2 infection and with:; • Asymptomatic CLL without treatment and undergoing observation, or CLL on BTK inhibitor or anti‐CD20 monoclonal antibodies; • Diagnosed with NSCLC and on chemotherapy, checkpoint inhibitors, or targeted agents for oncogene‐driven tumors; • Maintenance hemodialysis treatment due to end‐stage renal disease; • Immunomodulator therapy for an autoimmune inflammatory disorder; To describe the immune response to prophylactic BNT162b2 in participants =2 to <18 years of age without serological or virological evidence of past SARS‐CoV‐2 infection and either:; • Are on immunomodulator therapy for an autoimmune inflammatory disorder; • Are on immunosuppression therapy after solid organ transplant ; • Underwent bone marrow or stem cell transplant at least 6 months before enrollment ; Full information in Section 3 of Protocol Primary end point(s): In participants complying with the key protocol criteria (evaluable participants) and no serological or virological evidence of past SARS CoV‐2 infection in each disease subset: ; • GMTs at 1 month after Dose 2 ; In participants complying with the key protocol criteria (evaluable participants) and no serological or virological evidence of past SARS CoV‐2 infection in each age group (=2 to <5, =5 to <12, and =12 to <18 years) and disease subset: ; • GMTs at 1 month after Dose 2; In participants receiving at least 1 dose of study intervention in each disease subset, the percentage of participants reporting:; • Local reactions for up to 7 days following each dose; • Systemic events for up to 7 days following each dose; • AEs from Dose 1 through 1 month after Dose 2; • AEs from Dose 3 through 1 month after Dose 3; • from Dose 1 through the duration of the study ; In participants receiving at least 1 dose of study intervention in each age group (=2 to <5, =5 to <12, and =12 to <18 years) and disease subset, the percentage of participants reporting:; • Local reactions for up to 7 days following each dose; • Systemic events for up to 7 days following each dose; • AEs from Dose 1 through 1 month after Dose 2; • AEs from Dose 3 through 1 month after Dose 3; • SAEs from ose 1 through the duration of the study; ; • Incidence rate of confirmed COVID 19 per 1000 person‐years of follow‐up; • Incidence rate of confirmed MIS‐C cases Secondary Objective: Not Appllicable Timepoint(s) of evaluation of this end point: Please see Section 3 of full clinical Protocol

Euctr, D. K. (2021). "The effect of bladder installed local anesthetic solution prior to Botox injections in the bladder." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: Lidokain SAD Pharmaceutical Form: Injection INN or Proposed INN: Lidokain Other descriptive name: LIDOCAINE HYDROCHLORIDE PHEUR Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Injection Route of administration of the placebo: Intravesical use Trade Name: Natriumbikarbonat SAD Pharmaceutical Form: Injection INN or Proposed INN: Sodium hydrogen carbonat Other descriptive name: SODIUM HYDROGEN CARBONATE PHEUR Concentration unit: mmol/ml millimole(s)/millilitre Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Injection Route of administration of the placebo: Intravesical use Trade Name: Natriumklorid "Fresenius Kabi" 9 mg/ml Pharmaceutical Form: Solvent for parenteral use INN or Proposed INN: Sodium Chloride Other descriptive name: SODIUM CHLORIDE SOLUTION 0.9% Concentration unit: g/l gram(s)/litre Concentration type: equal Concentration number: 9‐ CONDITION: The effect of intravesical Lidocaine solution versus placebo on pain perception during intravesical injection of Onabotulinum toxin A. ; MedDRA version: 21.1 Level: LLT Classification code 10046495 Term: Urge incontinence syndrome System Organ Class: 100000004857 ; MedDRA version: 21.1 Level: LLT Classification code 10002321 Term: Anesthesia System Organ Class: 100000004852 Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Anesthesia and Analgesia [E03] PRIMARY OUTCOME: Main Objective: The purpose of this study is to investigate the effect of lidocaine‐solution versus placebo (isotonic NaCl) disposed inside the urinary bladder as intravesical anesthesia prior to onabotulinum toxin A injections in the treatment of urgency urinary incontinence.; Primary outcome is the maximum pain score reported by using the 100 mm visual analogue scale (VAS) immediately after the injection procedure. Primary end point(s): Primary end point is to reduce discomfort associated with onabotulinum toxin A injections and; ; Secondary Objective: Secondary outcome is adverse events: Post‐void residual requiring clean intermittent catherization (CIC), signs of urinary tract infection (UTI), hematuria, patient’s satisfaction on a 5‐point scale. Timepoint(s) of evaluation of this end point: 2021‐2024 SECONDARY OUTCOME: Secondary end point(s): Perform onabotulinum toxin A injections in outpatient clinics Timepoint(s) of evaluation of this end point: 2021‐2024 INCLUSION CRITERIA: • Female, age =18 years • Admitted to treatment with BTX‐A injections at the Urogynecological Clinic at Herlev Hospital due to UUI • Able to read and understand Danish • The female accepts to receive BTX‐A injection as an outpatient treatment without the option of receiving sedative drugs Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30

Euctr, D. K. (2021). "Glucocorticoids during robotoc-assisted hysterectomy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: Dexavit Product Name: Dexavit Product Code: H02AB02 Pharmaceutical Form: Concentrate and solvent for solution for infusion INN or Proposed INN: Dexavit CAS Number: 312‐93‐6 Other descriptive name: DEXAMETHASONE PHOSPHATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 24‐ Pharmaceutical form of the placebo: Infusion Route of administration of the placebo: Intravenous use CONDITION: robotic‐ assisted hysterectomy Therapeutic area: Body processes [G] ‐ Physical Phenomena [G01] PRIMARY OUTCOME: Main Objective: Gucocorticoid treatment to amelirate surgical stress parameters Primary end point(s): The primary endpoint is reduction of postoperative c‐reactive protein (crp) after robotic hysterectomy as an objective measurement of the stress amelioration by the given steroid. Secondary Objective: The hypothesis is that women undergoing robotic hysterectomy would benefit from peroperative glucocorticoid treatment on important life qualities like pain, fatigue, freedom of medications and resuming work and sexual activities. Timepoint(s) of evaluation of this end point: 24‐48 hours after surgery SECONDARY OUTCOME: Secondary end point(s): other inflammatory markers based on transcriptional profiling, pain and the medication needed during hospital stay and after discharge, and when work and sexual function could be resumed. Timepoint(s) of evaluation of this end point: Transcriptional factors: 2 days post surgery; Pain and medication before admittance by hosptal cahrst 24‐28 hours; Pain, medication, work sexual function fours weeks after discharge by questionnaires and diary INCLUSION CRITERIA: women who are having a robotic hysterectomy for benign indications: Meno‐metrorrhagia, dysmenorrhea, fibroma, dysplasia, dysmenorrhea, and ability in Danish writing Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Euctr, D. K. (2022). "Clinical research study to learn about the effect and safety of different doses of FE 999302 when given as a single dose for final development of the eggs after ovarian stimulation." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Code: FE 999302 Pharmaceutical Form: Solution for injection INN or Proposed INN: Choriogonadotropin beta Current Sponsor code: FE 999302 Other descriptive name: HUMAN CHORIONIC GONADOTROPIN Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 500‐ Trade Name: NOVAREL Product Name: NOVAREL Product Code: FE 999086 Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: Choriogonadotropin beta Current Sponsor code: FE 999086 Other descriptive name: HUMAN CHORIONIC GONADOTROPIN Concentration unit: IU international unit(s) Concentration type: equal Concentration number: 5000‐ Trade Name: OVITRELLE Product Name: OVITRELLE Pharmaceutical Form: Solution for injection in pre‐filled pen INN or Proposed INN: Choriogonadotropin alfa CAS Number: 177073‐44‐8 Other descriptive name: CHORIOGONADOTROPIN ALFA Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 250‐ Trade Name: OVITRELLE Product Name: OVITRELLE Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: Choriogonadotropin alfa CAS Number: 177073‐44‐8 Other descriptive name: choriogonadotropin alfa Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 500‐ CONDITION: Infertility ; MedDRA version: 20.1 Level: LLT Classification code 10016398 Term: Female infertility System Organ Class: 100000004872 Therapeutic area: Body processes [G] ‐ Reproductive physiologi cal processes [G08] PRIMARY OUTCOME: Main Objective: To compare the effect of 150, 200, and 250 µg of FE 999302 with 250 µg OVITRELLE and 10,000 IU NOVAREL on oocyte maturity when administered for triggering of final follicular maturation in women undergoing controlled ovarian stimulation Primary end point(s): Number of metaphase II (MII) oocytes Secondary Objective: 1. To compare the effect of 150, 200, and 250 µg of FE 999302 with 250 µg OVITRELLE and 10,000 IU NOVAREL on fertilisation, blastocyst quality, endocrine profile during the luteal phase, and pregnancy, when administered for triggering of final follicular; maturation in women undergoing controlled ovarian stimulation; 2. To compare the safety of 150, 200, and 250 µg of FE 999302 with 250 µg OVITRELLE and 10,000 IU NOVAREL when administered for triggering of final follicular maturation in women undergoing controlled ovarian stimulation; 3. To investigate the impact of body weight on FE 999302 exposure and assess the population pharmacokinetics of FE 999302 when administered for triggering of final follicular maturation in women undergoing controlled ovarian stimulation; Timepoint(s) of evaluation of this end point: 36 hours (+/‐ 2h) after triggering of final follicular maturation SECONDARY OUTCOME: Secondary end point(s): 1. Secondary Efficacy Endpoints; 1.1 Number of oocytes retrieved; 1.2 Number of fertilised (2 pronuclei) oocytes; 1.3 Number and quality of embryos; 1.4 Number and quality of blastocysts ; 1.5 Serum hormone concentrations of progesterone, 17‐OH‐progesterone, estradiol, follicle‐stimulating hormone (FSH), and luteinising hormone (LH) ; 1.6 Positive ßhCG (positive serum ßhCG test) ; 1.7 Clinical pregnancy (at least one gestational sac) ; 1.8 Vital pregnancy (at least one intrauterine gestational sac with fetal heart beat); 1.9 Ongoing pregnancy (at least one intrauterine viable fetus) ; ; 2. Secondary Pharmacokinetics Endpoint; 2.1 Serum hCG concentrations ; ; 3. Secondary Safety Endpoints; 3.1 Ovarian hyperstimulation syndrome (OHSS), overall and by grade and severity; 3.2 Injection site reactions (redness, pain, itching, swelling, and bruising) assessed by the; subject following administration of investigational medicinal product (IMP); 3.3 Treatment‐induced anti‐hCG antibodies, overall as well as with neutralising capacity; 3.4 Multi‐fetal gestation, biochemical pregnancy, spontaneous abortion, ectopic pregnancy; (with and without medical/surgical intervention), and vanishing twins; ; 4. x loratory Endpoint; 4.1 Biomarkers of oocyte maturation and/or OHSS in follicular fluid and granulosa cells Timepoint(s) of evaluation of this end point: 1.3 on day 3 after oocyte retrieval; 1.4 on day 5 after oocyte retrieval; 1.5 at end‐of‐stimulation, the day after triggering, at oocyte retrieval, on day 5 after oocyte retrieval (transfer), on day 7‐9 after oocyte retrieval (mid‐luteal phase), and 13‐15 days after transfer; 1.6 13‐15 days after transfer; 1.7 5‐6 weeks after transfer; 1.8 5‐6 weeks after transfer; 1.9 10‐11 weeks after transfer; 2.1 at end‐of‐stimulation, the day after triggering, at oocyte retrieval, on day 5 after oocyte retrieval (transfer), and on day 7‐9 after oocyte retrieval (mid‐luteal phase); 3. Secondary Safety Endpoints ongoing throughout the trial INCLUSION CRITERIA: 1. Subject informed consent form signed prior to any trial‐related activities. 2. Parental informed consent form signed prior to start of stimulation in the trial. 3. In good physical and mental health as judged by the investigator. 4. Pre‐menopausal women between the ages of 18 and 42 years. The subjects must be at least 18 years (including the 18th birthday) and no more than 42 years (up to the day before the 43rd birthday) when they sign the informed consent. 5. Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor. 6. Infertility for at least 1 year before screening for subjects <35 years or for at least 6 months for subjects =35 years (not applicable in case of tubal or severe male f

Euctr, D. K. (2023). "ACSE-ESMART." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Ribociclib Product Code: LEE011 Pharmaceutical Form: Capsule, hard INN or Proposed INN: RIBOCICLIB Current Sponsor code: LEE011 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ INN or Proposed INN: RIBOCICLIB Current Sponsor code: LEE011 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Product Name: Temozolomide Pharmaceutical Form: Capsule INN or Proposed INN: Temozolomide Other descriptive name: TEMOZOLOMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ INN or Proposed INN: Temozolomide Other descriptive name: TEMOZOLOMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ INN or Proposed INN: Temozolomide Other descriptive name: TEMOZOLOMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ INN or Proposed INN: Temozolomide Other descriptive name: TEMOZOLOMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Product Name: Olaparib Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Olaparib CAS Number: 763113‐22‐0 Other descriptive name: OLAPARIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ INN or Proposed INN: Olaparib CAS Number: 763113‐22‐0 Other descriptive name: OLAPARIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ INN or Proposed INN: Olaparib CAS Number: 763113‐22‐0 Other descriptive name: OLAPARIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Trade Name: KISQALI Product Name: Ribociclib Product Code: LEE011 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: RIBOCIC CONDITION: Relapsed or refractory tumors in children Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Phase I: To define or validate that the adult single agent RP2D of the selected drug or combination of drugs is safe in children/adolescents and/or that the PK profile is equivalent to that seen in adults, in pediatric/adolescent patients with malignancies which are recurrent or refractory to standard therapy. ; ; Phase II: To determine the preliminary activity (as measured by objective tumor response) of these agents in patients harboring specific molecular alterations or tumor types that may be associated with the mechanism of action of these drugs (i.e. molecularly enriched patient cohorts, where possible). Primary end point(s): The recommended phase II dose (RP2D) will be defined as the adult recommended dose (adjusted for weight or BSA) if toxicity and PK profiling are similar in children and in adults, or a higher dose, providing it is below the maximum tolerated dose (MTD).; The maximum tolerate dose (MTD) will be defined as the dose associated with or closest to 25% of DLTs in cycle 1.; Dose Limiting Toxicities (DLT) will be defined using CTC‐AE v4.03. Secondary Objective: Secondary:; 1.To characterize the toxicity profile of the agent(s) in pediatric/ adolescent patients.; 2.To characterize single or multiple‐dose PK of the agent(s).; 3.To evaluate the progression free survival and incidence of long responders (>6 months) and duration of response. ; 4.To evaluate whether the response rate is higher in the enriched population as compared to the non‐enriched population overall, by targeted treatment and by arm. ; ; Exploratory:; 1. To explore, define and/or validate pharmacodynamic (Pd) biomarkers of target inhibition or immune markers, where possible and potentially relevant.; 2. To explore relationships between measures of tumor expression of the molecular target(s), circulating tumor DNA and tumor growth. Timepoint(s) of evaluation of this end point: Cycle 1 SECONDARY OUTCOME: Secondary end point(s): Overall response rate (ORR), duration of response (DOR), progression‐free survival (PFS) ; ; Adverse Events ; ; PK parameters, including but not limited to pl ma concentration time profiles, AUClast, AUCtau, Cmin, Cmax, Tmax, Clearance, Half‐life time.; ; Relationship between the molecular profile of the tumor samples and tumor growth measured as modification of the sum of the diameters of the target lesions over time. Timepoint(s) of evaluation of this end point: Overall response rate (ORR), duration of response (DOR) will be defined as the time period between the first documented response (PR or CR) and the time of progression. Duration of response for patients free of progression at the cut‐off date will be censored at the last Imaging response scan date; progression‐free survival (PFS) will be defined as the time from treatment initiation until the date of first documented progression or death from any cause. Patients alive and free of progression at the cut‐off date will be censored at the last assessment date. INCLUSION CRITERIA: 1. Patients must be diagnosed with hematologic or solid tumor malignancy that has progressed or relapsed despite standard therapy, or for which no effective standard therapy exists. 2. Age <18 years at inclusion. 3. Patient must have had advanced molecular profiling (i.e. WES/WGS +/‐ RNAseq) of their recurrent or refractory tumor i.e. at the time of disease progression/relapse; exceptionally patients with advanced molecular profiling at diagnosis may be allowed. 4. Evaluable or measurable disease as defined by standard imaging criteria for the patient’s tumor type. 5. Performance status: Karnofsky performance status (for patients >12 years of age) or Lansky Play score (for patients =12 years of age) =70%. 6. Life expectancy =3 months. 7. Adequate organ function 8. Able to comply with scheduled follow‐up and with management of toxicity. 9. Females of childbearing potential must have a negative serum or urine pregnancy test within 7

Euctr, E. S. (2021). "Assessment of Conventional Dosing in Women undergoing ART with Follitropin Delta Treatment." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: REKOVELLE Pharmaceutical Form: Solution for injection in pre‐filled pen INN or Proposed INN: FOLLITROPIN DELTA CAS Number: 146479‐72‐3 Current Sponsor code: FE 999049 Other descriptive name: human recombinant follicle‐stimulating hormone Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 33.3‐ Trade Name: GONAL‐F Pharmaceutical Form: Solution for injection in pre‐filled pen INN or Proposed INN: follitropin alfa CAS Number: 56832‐30‐5 Other descriptive name: FOLLITROPIN ALFA Concentration unit: IU/ml international unit(s)/millilitre Concentration type: equal Concentration number: 600‐ CONDITION: Infertility in women undergoing assisted reproductive technologies (ART) such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle ; MedDRA version: 20.0 Level: PT Classification code 10021928 Term: Infertility female System Organ Class: 10038604 ‐ Reproductive system and breast disorders Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] PRIMARY OUTCOME: Main Objective: • To compare a starting dose of 15 µg REKOVELLE to a starting dose of 225 IU GONAL F in conventional regimens with respect to ovarian response in women undergoing controlled ovarian stimulation Primary end point(s): Number of oocytes retrieved Secondary Objective: • To compare the follicular development, endocrine profile and embryo development associated with conventional dosing of REKOVELLE and GONAL‐F; • To compare the treatment efficiency associated with conventional dosing of REKOVELLE and GONAL‐F; • To compare the safety profile associated with conventional dosing of REKOVELLE and GONAL‐F Timepoint(s) of evaluation of this end point: Oocyte retrieval will take place 36h (±2h) after triggering of final follicular maturation SECONDARY OUTCOME: Secondary end point(s): • Number of follicles (total and by size category) at end‐of‐stimulation; • Serum concentrations of estradiol and progesterone at end‐of‐stimulation; • Number of fertilised oocytes and fertilisation rate; • Number of embryos and blastocysts (total and by quality) ; • Total gonadotropin dose and number of stimulation days; • Early OHSS (overall and by grade) and/or preventive interventions for early OHSS Timepoint(s) of evaluation of this end point: Timepoint is included in the relevant endpoint INCLUSION CRITERIA: 1. Informed Consent Form signed prior to screening evaluations. 2. In good physical and mental health. 3. Pre‐menopausal females between the ages of 18 and 40 years. The subjects must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 40 years (up to the day before the 41st birthday) at the time of randomisation. 4. Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor. 5. Infertility for at least one year before randomisation for subjects =37 years or for at least 6 months for subjects =38 years (not applicable in case of tubal or severe male factor infertility). 6. Regular menstrual cycles of 21‐35 days (both inclusive), presumed to b

Euctr, E. S. (2021). "INTEnsity of ovariaN Stimulation and Embryo Quality." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: Ovaleap 900 UI/1,5 ml solucion inyectable Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Ovaleap 900 UI/1,5 ml solucion inyectable Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Ovaleap 450 UI/0,75 ml solucion inyectable Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Ovaleap 450 UI/0,75 ml solucion inyectable Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Ovaleap 300 UI/0,5 ml solucion inyectable Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Ovaleap 300 UI/0,5 ml solucion inyectable Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Orgalutran 0,25 mg/0,5 ml solución inyectable Pharmaceutical Form: Solution for injection Trade Name: Orgalutran 0,25 mg/0,5 ml solución inyectable Pharmaceutical Form: Solution for injection Trade Name: Ovitrelle 250 microgramos solución inyectable en pluma precargada. Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Ovitrelle 250 microgramos solución inyectable en pluma precargada. Pharmaceutical Form: Solution for injection in pre‐filled pen Trade Name: Decapeptyl diario 0,1 mg polvo y disolvente para solución inyectable Pharmaceutical Form: Solution for injection Trade Name: Decapeptyl diario 0,1 mg polvo y disolvente para solución inyectable Pharmaceutical Form: Solution for injection Trade Name: utrogestan 200 mg cápsulas blandas Pharmaceutical Form: Capsule, soft Trade Name: utrogestan 200 mg cápsulas blandas Pharmaceutical Form: Capsule, soft Trade Name: Omifin 50 mg comprimidos Pharmaceutical Form: CONDITION: Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] To compare the number of GQB and the morphokinetic parameters of early embryo development in infertile suboptimal patients undergoing two different intensities of ovarian stimulation, a milder approach ( Clomiphene Citrate (CC) 50mg/day plus 150IU daily dose of rFSH) and a more intense approach (300IU daily dose of rFSH). ; MedDRA version: 20.0 Level: PT Classification code 10021928 Term: Infertility female System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 21.0 Level: PT Classification code 10021926 Term: Infertility System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 20.0 Level: LLT Classification code 10021930 Term: Infertility NOS System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 20.0 Level: PT Classification code 10021929 Term: Infertility male System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 20.1 Level: LLT Classification code 10016399 Term: Female infertility (primary) System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 21.1 Level: LLT Classification code 10039843 Term: Secondary infertility (female) System Organ Class: 10038604 ‐ Reproductive system and breast disorders PRIMARY OUTCOME: Main Objective: To compare the two stimulation groups of Clomiphene Citrate (CC) 50mg/day plus rFSH 150IU vs. 300IU regarding the number of GQB according to the Istanbul Consensus criteria Primary end point(s): The primary efficacy endpoint is the number of GQB, according to the Istanbul Consensus Criteria . Secondary Objective: To compare the two stimulation groups of Clomiphene Citrate (CC) 50mg/day plus rFSH 150IU vs. 300IU regarding the morphokinetic parameters of early embryo development Timepoint(s) of evaluation of this end point: 5‐7 days from oocytes insemination procedure SECONDARY OUTCOME: Secondary end point(s): The key secondary endpoints are: ; 1. Time of pronuclei appearance; 2. Time of pronuclei disappearance; 3. The total number of embryos; 4. Time of division from 2 to 8 cells (t2, t3, t4, t5, t6, t7, t8); 5. Time of compactation; 6. Time of morula; 7. Time of cavitation/early blast; 8. Time of full blastul ion; 9. Time of expanded blastocyst ; 10. Time of hatching blastocyst; 11. Blastocyst formation rate; 12. Cycle cancelation rate Timepoint(s) of evaluation of this end point: 1‐7 days from oocytes insemination procedure INCLUSION CRITERIA: • AFC = 5 and = 10 • AMH =1.5 ng/ml (AMH result of up to one year will be valid) • Age = 35 years and =40 years • BMI >=18.5 and <25 kg/m2 • Willing to participate in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Euctr, E. S. (2021). "Trial of different schemes of PM14 alone and in combination with radiotherapy in soft tissue sarcomas and other solid tumors." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: PM14 Pharmaceutical Form: Lyophilisate for solution for infusion INN or Proposed INN: PM14 Other descriptive name: PM14 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 1‐ CONDITION: Advanced soft tissue sarcoma and other solid tumors Therapeutic area: Diseases [C] ‐ Cancer [C04] SECONDARY OUTCOME: Secondary end point(s): COHORTS A AND B; Phase I: ; ; ‐ Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.; ; • Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).; ; ‐ mPFS (according to central radiology review): Efficacy measured by mPFS, which is defined as the median of time in months from date of enrollment to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.; ; ‐ Quality of life: Assessed by using the EORTC QLQ‐C30 questionnaire.; ; ‐ The clinical study will provide tumor and blood samples for the translational research program.; ; ‐ The clinical study will provide blood samples for the measurement of PM14 concentration and baseline a‐1‐acid glycoprotein (AAG) levels.; ; COHORTS E AND F; Phase II:; ‐ Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).; ; ‐ mOS: Efficacy measured by mOS, which is defined as the median of time in months from date of enrollment to date of death due to any cause. OS will be censored on the last date a patient was known to be alive. ; ; ‐ Quality of life: Assessed by using the EORTC QLQ‐C30 questionnaire.; ; ‐ Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.; ; ‐ The clinical study will provide tumor and blood samples for the translational research program.; ; COHORT C; Phase I:; ‐ Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.; ; ‐ Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).; ; ‐ Median of progression‐free survival (mPFS) (according to central radiology review): Efficacy measured by mPFS, which is defined as the median of time in months from date of enrollment to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.; ; ‐ Quality of life: Assessed by using the EORTC QLQ‐C30 questionnaire.; ; ‐ The clinical study will provide tumor and blood samples for the translational research program.; ; Phase II:; • Changes in pain: Variations in pain will be measured by the Brief Pain Inventory – Short Form (BPI‐SF). ; ‐ This will be at least measured at baseline, an early assessment 1 week after RT completion, a delayed assessment on days 1 of cycles 2 and 3; and ultra‐delayed assessment at 6 months from the first day of treatment.; ‐ Worst pain (2‐point decrease or increase from baseline, respectively). ; ‐ The time to clinically relevant increase or decrease in worst pain (2‐point increase or decrease from baseline, respectively). ; ‐ The proportions of patients with moderate or severe worst pain at baseline (worst pain scor 4 points) who shifted to no or mild pain (worst pain score = 4 points) during the study. ; • Changes in analgesic use: Variations in analgesic use will be measured by the Analgesic Quantification Algorithm (AQA). ; ‐ This will be at least measured at baseline, an early assessment 1 week after RT completion, a delayed assessment on days 1 of cycles 2 and 3; and ultra‐delayed assessment at 6 months from the first day of treatment.; ‐ The proportion of patients with a shift from strong opioid use (score = 3) to no/low analgesic use (score = 2). ; ‐ The proportion of patients with a shift from no/low analgesic use to strong opioid use.; ‐ The proportion of patients with a low analgesic use (scores 1‐2) to no analgesic use (score 0). ; • Changes in quality of life: Variations in quality of life will be measured by the QLQ‐C30 EORTC v3.0 questionnaire. ; ‐ This will be at least measured at baseline, an early assessment 1 week after RT completion, a delayed assessment on days 1 of cycles 2 and 3; and ultra‐delayed assessment at 6 months from the first day of treatment.; ‐ The proportions of patients showing little (5‐10 points), moderate (11‐20 points) or high changes (> 20) in the physical, emotional, social and role functioning scales over time.; ; ; (INSUFFICIENT SPACE TO INCLUDE ALL THE INFORMATION. IT IS AVAILABLE IN THE SYNOPSIS.) Timepoint(s) of evaluation of this end point: ‐ ORR: central radiology review (end of treatment visit, 3 weeks after surgery); ‐ mPFS: median of time in months from date of enrollment to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.; ‐ Biological samples for translational study: baseline and cycle 1 day 2 or 3; ‐ mOS: median of time in months from date of enrollment to date of death due to any cause; ‐ Changes in pain, in analgesic use and in quality of life: at least measured at baseline, an early assessment 1 week after RT completion, a delayed assessment on days 1 of cycles 2 and 3; and ultra‐delayed assessment at 6 months from the first day of treatment.; ; (INSUFFICIENT SPACE TO INCLUDE ALL THE INFORMATION. IT IS AVAILABLE IN THE SYNOPSIS.) INCLUSION CRITERIA: All the cohorts: ‐ The patient must voluntarily sign the informed consent before any study test is conducted that is not part of routine patient care. ‐ Age: 18‐75 years. ‐ Measurable disease according to RECIST v1.1 criteria. ‐ Performance status =1 (ECOG). ‐ Men or women of childbearing potential must be using an effective method of contraception before entry into the study and throughout the same and for 3 months (men) and 6 months (women) after ending study treatment. Women of childbearing potential must have a negative serum or urine pregnancy test before study entry. ‐ Normal cardiac function with a LVEF = 50% by echocardiogram or MUGA. ‐ HBV and HCV serologies must be performed prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lam PRIMARY OUTCOME: Main Objective: COHORTS A (24‐h IV PM14 in advanced sarcomas) and B (3‐h IV PM14 3 consecutive days in advanced sarcomas); Phase I: To determine the maximum tolerated dose (MTD) of PM14 to be used as recommended phase 2 dose (RP2D).; ; COHORTS E (24‐h IV PM14 or 3‐h IV PM14 3 consecutive days ‐ Expanded to advanced L‐sarcomas) and F (24‐h IV PM14 or 3‐h IV PM14 3 consecutive days ‐ Expanded to other advanced STS: non L‐sarcomas); Phase II: To evaluate the progression‐free survival rate (PFSR) at 6 months.; ; COHORT C (Best scheme of PM14 plus RTP (3 Gy x 10 days = 30 Gy) in advanced solid tumors: sarcoma, head and neck, and others); Phase I: To determine the MTD of PM14 to be used as RP2D.; Phase II: To evaluate the ORR in irradiated nodules only. This objective is considered as a surrogate of palliative relief. ; ; COHORT D (Best schem o PM14 + RTP (1.8 Gy x 25 days = 45 Gy) in localized intermediate sarcoma); Phase I: To determine the MTD of PM14 to be used as RP2D.; Phase II: To evaluate the ORR. Primary end point(s): COHORTS A AND B; Phase I: The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose‐limiting toxicities detailed in the protocol.; ; COHORTS E AND F; Phase II: PFSR‐6m (according to central radiology review): Efficacy measured by the PFSR at 6 months, which is defined as the percentage of patients who did not experience radiological progression according to RECIST v1.1 or death due to any cause since the date of enrollment until month 6 after date of enrollment.; ; COHORT C; Phase I: The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose‐limiting toxicities detailed in the protocol.; ; Phase II: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1). Only nodules included in the radiation field will be considered. Secondary Objective: COHORTS A AND B; Phase I:; ‐ To evaluate the safety profile.; ‐ To evaluate the overall response rate (ORR).; ‐ To evaluate the median of progression‐free survival (mPFS).; ‐ To evaluate quality of life.; ‐ To contribute to translational studies.; ‐ To characterize the PK of PM14 in the explored regimens; ; COHORTS E AND F; Phase II:; ‐ To evaluate the overall response rate (ORR).; ‐ To evaluate the median of overall survival (mOS).; ‐ To evaluate quality of life.; ‐ To evaluate the safety profile.; ‐ To contribute to translational studies.; ; COHORT C; Phase I:; ‐ To evaluate the safety profile.; ‐ To evaluate the overall response rate (ORR).; ‐ To evaluate the median of progression‐free survival (mPFS).; ‐ To evaluate quality of life.; ‐ To contribute to translational studies.; ; Phase II:; ‐ To evaluate variations in pain. /‐ To evaluate variations in analgesic use. ; ; (INSUFFICIENT SPACE TO INCLUDE ALL THE INFORMATION. IT IS AVAILABLE IN THE SYNOPSIS.) Timepoint(s) of evaluation of this end point: PFSR: since the date of enrollment until month 6 after date of enrollment.; ORR: central radiology review (end of treatment visit, 3 weeks after surgery)

Euctr, E. S. (2021). "Umbilical cord plasma for treating endometrial pathologies (thin endometrium / Ash erman’s syndrome/ endometria atrophy)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Platelet‐rich plasma from umbilical cord. Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: platelet rich plasma, allogenic Other descriptive name: HUMAN PLATELET, ALLOGENIC Concentration unit: ml millilitre(s) Concentration type: range Concentration number: 2‐6 CONDITION: Endometrial pathologies (Thin endometrium/ Asherman's syndrome/ Endometrial atrophy) Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] PRIMARY OUTCOME: Main Objective: Study of endometrial regeneration and/or improvement, in the form of tissue thickening, in patients with endometrial pathologies ; (thin endometrium/Asherman's syndrome/endometrial atrophy) treated with platelet‐rich plasma from the umbilical cord. Primary end point(s): Increase in endometrial thickness after application of PRP treatment, calculated as the difference between the endometrium after application of the treatment and the thickness of the patient's initial endometrium (in mm) Secondary Objective: Evaluation of the proof of concept in the 3 arms of the group of patients with premature ovarian failure (group A).; Study of the rates of implantation, pregnancy, abortion and live newborn after injection of the investigational drug (platelet‐rich plasma from umbilical cord) in the group of patients with endometrial pathology (group B).; Evaluation at the genetic and protein level of the endometrial biopsies collected from both groups (A and B).; Study of the molecular composition of the different plasma fractions obtained from the collected umbilical cord samples; Adverse events collection Timepoint(s) of evaluation of this end point: After application of PRP treatment SECONDARY OUTCOME: Secondary end point(s): Proof of concept.; Implementation rate.; Pregnancy rate.; Abortion rate.; Live birth rate.; Evaluation at the genetic and protein level of the endometrial biopsies collected from both groups (A and B).; Study of the molecular composition of the different plasma fractions obtained from the collected umbilical cord samples; Adverse events collection Timepoint(s) of evaluation of this end point: Proof of concept._Comparisons of endometrial thickness growth before and after PRP treatment, according to subgroups (grupo A) at the end of study; ; Study of the rates of implantation, pregnancy, abortion and live newborn after injection of the investigational drug (platelet‐rich plasma from umbilical cord) in the group of patients with endometrial pathology (group B), will be analized at the end of the study.; ; Composition molecular of the plasma fractions of the PRP samples of the umbilical cord used, Protein and genetic pattern of the collected endometrial biopsies before and after applying the PRP treatment, will be analysed at the end of the study.; ; Adverse effects, during all study. INCLUSION CRITERIA: Umbilical cord blood donors: information and informed consent of the parent(s), umbilical cord blood from live births in the obstetrics and gynaecology department of the HUP La Fe; the same criteria for collecting umbilical cord blood as standardised in the HUP La Fe will be followed for the donation of this biological product. Patients group A: information and signed informed consent; woman, acting voluntarily, aged between 18 and 48 at the time of recruitment; body mass index (BMI): = 18 kg/m2 and = 35 kg/m2; patients with premature ovarian failure (amenorrhea before age 40 and FSH > 40 IU/L). Group B patients: information and signed informed consent; female, acting voluntarily, aged between 18 and 48 years at the time of recruitment; body mass index (BMI): = 18 kg/m2 and = 35 kg/m2; patients undergoing a cycle of assisted reproduction; endometrial thickness < 5mm despite the administration of oestrogens for more than 10 days and/or evidence of Asherman'

Euctr, F. I. (2021). "Infections after hysterectomy - a double blinded placebo controlled study comparing the profylactic use of azithromycin and cefuroxime with single cefuroxime." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: AZITHROMYCIN Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: AZITHROMYCIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Post‐hysterectomy infections Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: Primary outcome of the study is to assess whether azithromycin + cefuroxime decreases post‐hysterectomy deep infections (wound infections beneath fascia + deep pelvic area infections) as compared to cefuroxime only prophylaxis during 30 days after hysterectomy. Primary end point(s): All infection episodes will be reported up to 30 days postoperatively:; ; 1. Deep wound and pelvic organ infections; ; 2. Surficial infections; ; 3. Other infections, such has urine tract infections, fever over 38 ? over 2 days. Secondary Objective: Secondary outcomes are to assess whether azithromycin + cefuroxime decreases post‐hysterectomy superficial infections, urinary tract infections, or post‐operative fever as compared to cefuroxime only, and to report possible side‐effects of the used antibiotics.; ; In addition, the study finds out a possible role of BV and microbiome in post‐hysterectomy infections. Timepoint(s) of evaluation of this end point: 30 days after the operation. SECONDARY OUTCOME: Secondary end point(s): No. Timepoint(s) of evaluation of this end point: No. INCLUSION CRITERIA: Women undergoing hysterectomy for benign indication in University Hospitals (Helsinki University Hospital, Turku University Hospital, Tampere University Hospital, Oulu University Hospital and Kuopio University Hospital) who have not any contraindications for azithromycin or cefuroxime. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 1550 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 700

Euctr, F. I. (2021). "Pembrolizumab/placebo plus paclitaxel with or without bevacizumab for platinum-resistant recurrent ovarian cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: KEYTRUDA® (Pembrolizumab, MK‐3475) Product Code: MK‐3475 Pharmaceutical Form: Solution for infusion INN or Proposed INN: Pembrolizumab CAS Number: 1374853‐91‐4 Current Sponsor code: MK‐3475 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Platinum‐resistant Recurrent Ovarian Cancer ; MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression‐free survival (PFS) per RECIST 1.1 as assessed by the investigator Primary end point(s): 1. Progression‐free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator Secondary Objective: 1. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to overall survival (OS) ; 2. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to PFS per RECIST 1.1 by blinded independent central review (BICR) for PD‐L1+ (CPS =1) and all participants; 3. To evaluate safety and tolerability of pembrolizumab plus paclitaxel with or without bevacizumab; 4. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to Global Health Status/Quality of Life (GHS/QoL) score using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ‐C30) and abdominal/gastrointestinal (GI) symptoms using EORTC Ovarian Cancer‐Specific Quality of Life Questionnaire (QLQ‐OV28) for PD‐L1+ (CPS =1) and all participants Timepoint(s) of evaluation of this end point: 1. Up to 38 months 64 months; 2. Up to 38 months; 3. Up to 64 months; 4. Up to 64 months; 5. Baseline and up to 64 months; 6. Up to 64 months; 7. Baseline and up to 64 months; 8. Up to 64 months SECONDARY OUTCOME: Secondary end point(s): 1. Overall Survival (OS); 2. PFS per RECIST 1.1 by Blinded Independent Central Review (BICR); 3. Number of Participants who Experience an Adverse Event (AE); 4. Number of Participants who Discontinue Study Treatment due to an AE; 5. Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30) ; 6. Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ‐C30; 7. Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire‐Ovarian Cancer (QLQ‐OV28) Abdominal/GI Symptom Scale; 8. TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ‐OV28 Abdominal/GI Symptom Scale Timepoint(s) of evaluation of this end point: 1. Up to INCLUSION CRITERIA: A participant will be eligible for inclusion in the study if the participant meets the following criteria: 1. Has histologically confirmed epithelial (including high‐grade serous or predominantly serous, low‐grade serous, any‐grade endometrioid, malignant mixed Müllerian tumors [carcinosarcoma], or clear cell) ovarian, fallopian tube, or primary peritoneal carcinoma. 2. Has received 1 or 2 prior lines of systemic therapy for OC, including at least 1 prior platinum‐based therapy. – Participants must have received at least 4 cycles of platinum‐based therapy in first line. – Adjuvant ± neoadjuvant therapy is considered 1 line – Participants may have received a pri PARPi; this will not be considered a separate line of therapy if received in maintenance – Participants may have received a prior anti‐PD‐1/anti‐PD‐L1 therapy or bevacizumab; these will not be considered a separate line of therapy – Any chemotherapy regimen change due to toxicity in

Euctr, F. R. (2021). "Evaluation of an initial treatment with bevacizumab in combination with chemotherapy and then in combination with niraparib in maintenance in patients with advanced ovarian cancer after complete initial surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: ZEJULA Product Name: NIRAPARIB Pharmaceutical Form: Capsule, hard INN or Proposed INN: Niraparib CAS Number: 1038915‐60‐4 Concentration unit: mg milligram(s) Concentration type: range Concentration number: 200 ‐300 Trade Name: MVASI Product Name: Bevacizumab Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Bevacizumab CAS Number: 216974‐75‐3 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ CONDITION: Advanced ovarian, tubal or peritoneal cancer ; MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Determine whether paclitaxel – carboplatin followed by maintenance with niraparib compared to paclitaxel – carboplatin – Bevacizumab followed by maintenance Niraparib + Bevacizumab following a Front‐Line Complete Cytoreductive Surgery improves the progression‐free survival rate at 24 months in patients with advance ovarian cancer, primary peritoneal cancer and/or fallopian‐tube cancer. Primary end point(s): Progression‐free survival rate at 24 months Secondary Objective: ‐ Evaluate Progression Free Survival (PFS); ‐ Evaluate Progression Free Survival 2 (PFS2); ‐ Evaluate Safety (assessed based on CTCAE version 5); ‐ Evaluate Time to First Subsequent Treatment (TFST); ‐ Evaluate Time to Second Subsequent Treatment (TSST); ‐ Evaluate Overall survival (OS) at 5 years; ‐ Confirm the predictive value (overall chemo‐sensitivity) of the KELIM (CA‐125 Elimination rate constant K) Timepoint(s) of evaluation of this end point: 24 months after randomization of the last patient (estimated date: Q4 2025) SECONDARY OUTCOME: Secondary end point(s): ‐ Progression Free Survival (PFS); ‐ Progression Free Survival 2 (PFS2); ‐ Safety (assessed based on CTCAE version 5); ‐ Time to First Subsequent Treatment (TFST); ‐ Time to Second Subsequent Treatment (TSST); ‐ Overall survival (OS) at 5 years; ‐ Confirm the predictive value (overall chemo‐sensitivity) of the KELIM (CA‐125 Elimination rate constant K) Timepoint(s) of evaluation of this end point: PFS, PFS2, OS (estimated date: Q4 2028) INCLUSION CRITERIA: 1. Female patient = 18 years of age. 2. Signed informed consent and ability to comply with treatment and follow‐up. 3. Patient with newly diagnosed, a. Ovarian cancer, primary peritoneal cancer and/or fallopian‐tube cancer, b. Histologically confirmed (based on local histopathological findings): • high grade serous or • high grade endometrioid (grade 2 and 3) or • other epithelial non mucinous and non‐clear cell ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation, c. At an advanced stage: FIGO stage IIIA to IIIC of the 2018 FIGO classification. 4. Patient having undergone frontline, complete cytoreductive surgery (i.e. no visible residual disease): The patient will be considered eligible once the ESGO Quality Assurance in Ovarian Cancer Surgery will have been filled out and validated 5. Eastern Cooperative Oncology Group (ECOG) performance status 0‐1. 6. Patient must have received one cycle of carboplat

Euctr, F. R. (2021). "A Multicenter, Open-Label Phase 1/2 Trial to Assess the Safety, Tolerability and the Efficaciousness of MORAb-202, which is a type of drug called antibody-drug conjugate (ADC) that targets folate receptor alpha (FRa) in subjects with selected tumor types." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Code: MORAb‐202 Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: Not assigned CAS Number: 2407465‐18‐1 Current Sponsor code: MORAb‐202 Other descriptive name: Farletuzumab‐[Mal‐PEG2‐Val‐Cit‐pAB‐eribulin] Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ CONDITION: Solid tumors expressing folate receptor alpha in 4 tumor types: platinum resistant ovarian cancer, triple‐negative breast cancer (TNBC), endometrial cancer (EC), and non‐small cell lung cancer adenocarcinoma; NSCLC). ; MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non‐small cell lung cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] SECONDARY OUTCOME: Secondary end point(s): The secondary efficacy endpoints of the study are DOR, DCR, CBR, PFS by RECIST 1.1, and OS. ; Other secondary endpoints of the study include safety endpoints, PK profile, and the relationship between FRA expression levels and clinical outcome: ; Safety Endpoints: clinical laboratory tests, vital signs, oxygen saturation, body weight, 12‐lead ECGs, ECOG PS, and serum ADA titer (semi‐quantitative test) (not identified in an ongoing manner, identified during study analyses). ; The PK profile of MORAb‐202/total antibody/released eribulin in serum and plasma, and the assessment of potential ADA to MORAb‐202. ; The relationship between FRA expression levels and clinical outcome. Timepoint(s) of evaluation of this end point: DOR:From the 1st date of documented CR or PR to the date of disease progression or death, whichever occurs first. Calculated for subjects whose BOR is CR or PR. ; DCR:Proportion of subjects with BOR of CR, PR, or SD. ; CBR:Proportion of subjects with BOR of CR, PR, or durable SD (=23 weeks). SD is defined as the time from the date of 1st dose to the date of the 1st documentation of disease progression or death, whichever occurs first. Calculated for subjects whose BOR is SD. ; PFS:From the date of 1st dose to the date of the 1st documentation of disease progression or death, whichever occurs first. ; OS:From the date 1st dose to the date of death or for the subjects alive or lost to follow up, date of last known alive or the date of data cutoff, whichever comes first. ; PRIMARY OUTCOME: Main Objective: Primary Objectives; Dose‐Escalation Part primary objective:; (1) To evaluate safety, tolerability and to determine the recommended Phase 2 dose (RP2D) of MORAb‐202 in subjects with selected tumor types (ovarian cancer [OC], endometrial cancer [EC], non‐small cell lung carcinoma [NSCLC], triple‐negative breast cancer [TNBC]).; Dose‐Confirmation Part primary objectives:; To further evaluate the safety and tolerability of MORAb‐202.; To evaluate preliminary efficacy measured by objective response rate (ORR) of MORAb‐202 in subjects with OC and EC at selected doses.; ; ; Primary end point(s): The primary endpoints are:; RP2D of MORAb‐202 (Dose‐Escalation Part only).; ORR: defined as the proportion of subjects achieving a best overall response (BOR) of complete response (CR) or partial response (PR) (BOR ‐ are CR, PR, SD, PD, and not evaluable (NE), where SD has to be achieved at =5 weeks after the first dose 24 weeks after C1D1. All responses of CR and PR must be confirmed no less than 28 days following the initial achievem t of the response.; Safety Endpoints: DLTs, AEs,(SAEs, AEs leading to treatment discontinuation) and AEIs (including ILD incidence, severity, duration and outcome, and deaths). Secondary Objective: Secondary Objectives:; ‐ To evaluate duration of response (DOR), disease control rate (DCR), and clinical benefit rate (CBR).; ‐ To evaluate progression‐free survival (PFS) and overall survival (OS).; ‐ To determine the pharmacokinetic (PK) profiles of MORAb‐202, total antibody, and released eribulin in serum or plasma. ; ‐To evaluate the relationship between folate receptor alpha (FRA) expression levels and clinical outcome measures to support the identification of an appropriate FRA cut off point.; ; ; Timepoint(s) of evaluation of this end point: Efficacy analyses will be conducted based on the Efficacy Analysis Set. The primary efficacy analysis for a tumor type will be performed when all subjects in the cohort have completed the Week 24 tumor assessment or discontinued study treatment or when the study is terminated by the sponsor. INCLUSION CRITERIA: 1. Aged =18 years 2. For Dose‐Escalation: Females (TNBC, EC and OC) or males/females (NSCLC adenocarcinoma). Subjects with the following disease characteristics: a. TNBC: Histologically confirmed diagnosis of metastatic TNBC (ie, estrogen receptor (ER) negative/progesterone receptor negative/ human epidermal growth factor receptor 2 (HER2) negative (defined as IHC <2+ or fluorescence in situ hybridization (FISH) negative) breast cancer). Previously treated with at least one line of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. b. NSCLC adenocarcinoma: Histologically or cytologically confirmed metastatic NSCLC adenocarcinoma: subjects who have failed previous treatment for metastatic disease, are not indicated or failed epidermal growth factor receptor (EGFR)‐, ALK‐, BRAF‐ or ROS1‐targeted therapy, and for whom no alternative standard therapy exists c. EC: Histologically confirmed diag

Euctr, G. R. (2023). "A Phase 1/2a Study Evaluating Allocetra-OTS on its own or together with Anti-PD-1 Therapy for the Treatment of Advanced Solid Tumor Malignancy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Allocetra‐OTS Pharmaceutical Form: Suspension for injection INN or Proposed INN: Allocetra‐OTS Other descriptive name: Allogeneic mononuclear cells induced to an apoptotic state Concentration unit: Other Concentration type: equal Concentration number: 2500000000‐ Trade Name: OPDIVO Product Name: Opdivo Product Code: Sterile Concentrate Pharmaceutical Form: Sterile concentrate INN or Proposed INN: Nivolumab CAS Number: 946414‐94‐4 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ CONDITION: Advanced Solid Tumor Malignancy ; MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: 1. To assess the safety and to identify the MTD of Allocetra‐OTS as monotherapy when repeatedly administered via IV or IP infusion in patients with advanced solid tumor malignancy (applicable to Stage 1).; 2. To assess the safety and to identify the MTD of Allocetra‐OTS administered via IV or IP infusion in combination with nivolumab in patients with advanced solid tumor malignancy (applicable to Stage 2). Primary end point(s): 1. Stage 1: Characterize the safety of Allocetra‐OTS from the first infusion of Allocetra‐OTS up to Day 21, based on the DLTs and MTD (or MAD if no MTD is defined) of Allocetra‐OTS as monotherapy.; 2. Stage 2: Characterize the safety of Allocetra‐OTS from the first infusion of Allocetra‐OTS up to Day 35, based on the DLTs and MTD (or MAD if no MTD is defined) of Allocetra‐OTS in combination with nivolumab. Secondary Objective: 1. To assess preliminary efficacy parameters following IV or IP administration of Allocetra‐OTS as monotherapy in patients with advanced solid tumor malignancy (applicable to Stage 1).; 2. To assess preliminary efficacy parameters following IV or IP administration of Allocetra‐OTS in combination with nivolumab in patients with advanced solid tumor malignancy (applicable to Stage 2) Timepoint(s) of evaluation of this end point: Day 21 and Day 35 SECONDARY OUTCOME: Secondary end point(s): 1. Overall Response Rate (ORR)/Best Overall Response Rate (BORR) (percentage of patients who achieve best response of complete response [CR] or partial response [PR]).; 2. Clinical benefit rate (CBR) (percentage of patients who achieve best response of CR, PR or stable disease [SD] =6 months). (Stage 1 and 2); 3. Duration of response (DoR), defined as the time from first documented evidence of CR or PR until disease progression or death.; 4. Time to response (TTR), defined as the time from first infusion of AllocetraOTS to the first documented CR or PR.; 5. Kaplan‐Meier estimated median progression‐free survival (PFS), defined as the time from the first infusion of Allocetra‐OTS to disease progression or death due to any cause, whichever occurs first.; 6. Kaplan‐Meier estimated median overall survival (OS) defined as the time from the first infusion of Allocetra‐OTS to death due to any cause.; Note: All secondary endpoints are applicable to both Stage 1 and Stage 2 of the study, unless otherwise specified Timepoint(s) of evaluation of this end point: 12 months INCLUSION CRITERIA: 1. Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumors, that have relapsed or have been refractory to available approved therapies specific to their cancer type, based upon standard clinical practice guidelines, with agents that are approved and available to them in their country. Patients who are either not eligible for or have specifically declined additional standard of care systemic therapy may also be enrolled. Patients with peritoneal carcinomatosis with no or minimal extraperitoneal disease (as per Investigator discretion) can be eligible for treatment with IP Allocetra‐OTS if an appropriate IP catheter (e.g. PleurX) or port is in place or can be placed. 2. Patients must have measurable disease per esponse Evaluation Criteria in Solid Tumors (RECIST v1.1), assessed within 28 days prior to study treatment. 3. Age =18 years old at the time of signing the ICF. 4. Patients who have

Euctr, H. U. (2021). "A Phase II, Randomized, Parallel design, Open label, Dose ranging Study to evaluate the efficacy and safety of Furazidin vaginal tablets in women with bacterial vaginosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Furazidin, vaginal tablets, 5 mg Pharmaceutical Form: Vaginal tablet INN or Proposed INN: Furazidin CAS Number: 1672‐88‐4 Other descriptive name: FURAZIDINE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Product Name: Furazidin, vaginal tablets, 25mg Pharmaceutical Form: Vaginal tablet INN or Proposed INN: Furazidin CAS Number: 1672‐88‐4 Other descriptive name: FURAZIDINE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Product Name: Furazidin, vaginal tablets, 50mg Pharmaceutical Form: Vaginal tablet INN or Proposed INN: Furazidin CAS Number: 1672‐88‐4 Other descriptive name: FURAZIDINE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Product Name: Furazidin, vaginal tablets, 100mg Pharmaceutical Form: Vaginal tablet INN or Proposed INN: Furazidin CAS Number: 1672‐88‐4 Other descriptive name: FURAZIDINE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Dalacin 2% Vaginal Cream Product Name: Dalacin 2% Vaginal Cream Pharmaceutical Form: Vaginal cream INN or Proposed INN: clindamycin phosphate CAS Number: 24729‐96‐2 Other descriptive name: CLINDAMYCIN PHOSPHATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ CONDITION: Bacterial Vaginosis (BV) ; MedDRA version: 20.1 Level: PT Classification code 10004055 Term: Bacterial vaginosis System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] SECONDARY OUTCOME: Secondary end point(s): 1. Day 5 assessment of clinical cure rate based on the Amsel criteria (vaginal pH > 4.5, presence of clue cells, KOH test as well as greyish white, malodorous discharge), where clinical cure is defined as: the resolution of the abnormal vaginal discharge, a negative whiff test, and the presence of clue cells at less than 20% of the total epithelial cells on microscopic examination of the saline wet mount.; 2. Percentage of subjects with Nugent score of less than 4 (Day 21‐30); 3. Percentage of responders with outcome defined as a clinical cure plus Nugent score of less than 4 (Day 21‐30); 4. Assessment of patient quality of life with 5 treatments modalities (from the baseline visit to the end of the treatment); 5. Assessment of the patients’ compliance; 6. The percentage of Bacterial Vaginosis recurrences within 12 weeks of follow‐up; Timepoint(s) of evaluation of this end point: Day 5 PRIMARY OUTCOME: Main Objective: To evaluate the safety and efficacy of Furazidin vaginal tablets in patients with Bacterial Vaginosis.; To perform a proof of concept study to establish the most appropriate dosage (dosage regimen and treatment duration) to take forth into a phase III trial. Four different doses of study drugs as well as the comparator (Clindamycin cream 2%) will be applied vaginally to adult women with clinical signs and symptoms of vaginal infections caused by Bacteria spp.; In addition, the safety and local tolerability of four tested doses of the study drug will be assessed.; Primary end point(s): 1. Safety and local tolerability – incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) related and unrelated to IMP.; Safety and local tolerability assessment based on Likert scale of the signs/symptoms:; • Assessed by physician:; Verbal evaluation of local symptoms and naked eye inspection of visible epithelial surface will be performed. Patients will be questioned and clinician will verify the following symptomps according to the Likert like scale (NO, MILD, MODERATE, MODERATE TO SEVERE, SEVERE):; o Discharge (normal/abnormal); o Dysuria; o Irritation; o Puffiness ; o Hyperemia of the mucosa ; ; • Reported by patient; Self‐reporting evaluations will be performed by patients according to the Likert like scale (NO, MILD, MODERATE, MODERATE TO SEVERE, SEVERE):; o Burning; o Discharge (normal/abnormal); o Dysuria; o Discomfort; I ritation; o Itching; o Pain; ; 2. Clinical endpoint – the Day 8 assessment of clinical cure rate based on the Amsel criteria (vaginal pH > 4.5, presence of clue cells, KOH test as well as greyish white, malodorous discharge), where clinical cure is defined as: the resolution of the abnormal vaginal discharge, a negative whiff test, and the presence of clue cells at less than 20% of the total epithelial cells on microscopic examination of the saline wet mount. Secondary Objective: not applicable Timepoint(s) of evaluation of this end point: Day 8 INCLUSION CRITERIA: 1. A written informed consent signed before any study‐specific evaluation is performed. 2. Female patients with age = 18 and = 50 years. 3. Patients requiring treatment for bacterial vaginosis. 4. Papanicolaou (Pap) smear/tests will be performed for subjects who do not have a negative test for intraepithelial lesion or malignancy or atypical squamous cells of undetermined significance in the past 24 months; in circumstances where the results of the Pap smear are pending at the time of randomization, eligible subjects may be randomized. 5. Women of childbearing potential must have a negative pregnancy test before randomization and may not be lactating or planning to become pregnant during the study period (up to Follow Up Visit 4 – Day 21‐30). 6. Agreement of female subject of childbearing potential to use highly effective methods of contraception (progestin intrauterine device, all oral contraceptives, transdermal hormonal contraceptives) or to a

Euctr, I. T. (2021). "Clinical study, involving Italian clinical sites, comparing the activity of Paclitaxel (weekly administration) to the activity of Cediranib-Olaparib with continuous administration or to Cediranib-Olaparib with intermittent administration, in patients with advanced ovarian cancer, resistant to previous platinum treatment." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Cediranib Product Code: [Not Applicable] Pharmaceutical Form: Tablet INN or Proposed INN: 8764 CAS Number: 288383‐20‐0 Current Sponsor code: AZD2171 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Product Name: Olaparib Product Code: [Not applicable] Pharmaceutical Form: Tablet INN or Proposed INN: Olaparib, 8685 CAS Number: 763113‐22‐0 Current Sponsor code: AZD2281‐KU‐0059436 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 600‐ Trade Name: PACLITAXEL MYLAN GENERICS ‐ 6 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 16.7 ML Product Name: Paclitaxel Product Code: [n.a.] Pharmaceutical Form: Solution for infusion INN or Proposed INN: Paclitaxel, 7052 CAS Number: 33069‐62‐4 Current Sponsor code: n.a. Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 80‐ CONDITION: resistant high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. ; MedDRA version: 21.1 Level: PT Classification code 10070907 Term: Ovarian cancer stage III System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10070908 Term: Ovarian cancer stage IV System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] PRIMARY OUTCOME: Main Objective: The main objective of the trial is to evaluate and to compare the efficacy of the combination of Olaparib and Cediranib to the efficacy of weekly Paclitaxel administration, in terms of time to disease progression.; The study has also as main objective the safety evaluation of the new intermittent schedule of Cediranib compared to the administration of Cediranib with continuous schedule in terms of gastro‐intestinal toxicity. ; ; ; Primary end point(s): The study primary endpoint will be the progression free survival (PFS) defined as the time from randomization to the date of first progression or death for any cause, whichever comes first.; Progression will be established as the radiological disease progression according to RECIST 1.1 or to clinical assessment in case radiological evaluation is not feasible due to clinical condition.; The primary endpoint for safety will be the number of evacuations per day.; ; Secondary Objective: Secondary efficacy objectives will be the evaluation of treatment response, the prolongation of the time to second progression, overall survival and quality of life.; Other study aims will be to assess the safety and tolerability of combination of Olaparib and Cediranib vs. paclitaxel as single agent chemotherapy and the compliance to the study treatments.; Timepoint(s) of evaluation of this end point: Disease progression will be evaluated at the end of every 8 weeks (+/‐ 1 week) from randomisation for 48 weeks and every 12 weeks (+/‐ 1 week) thereafter. Safety primary endopoint: number of evacuations will be recorded by the patients every day during whole treatment period. SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints will be: ; ‐ Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1; ‐ PFS2 defined as time from randomization to second disease progression according to RECIST 1.1 or to clinical assessment, or death by any cause. ; ‐ Overall Survival (OS), defined in each patient as the time from randomization to the date of death for any cause.; ‐ Quality of Life evaluated by the Functional Assessment of Cancer Therapy‐Ovarian (FACT‐O) questionnaire.; ; ; Secondary endpoints of safety will be: ; ‐ the maximum toxicity grade experienced by each patient, for each toxicity, according to NCI‐CTCAE v. 4.0; ; ‐ the number of patients experiencing grade 3‐4 toxicity for each toxicity; ; ‐ type, frequency and ature of SAEs; ; ‐ patients with at least a SAE; patients with at least a SADR; ; ‐ patients with at least a SUSAR.; ; The endpoints for compliance will be: number of administered cycles, reasons for discontinuation and treatment modification and dose intensity.; Timepoint(s) of evaluation of this end point: Efficacy: second disease progression evaluated every 12 weeks from first progression. ORR according to radiological disease assessment, performed every 8 weeks from random until the end of treatment and every 12 weeks thereafter. ; Survival evaluated every 12 weeks from the first disease progression until overall survival analysis. ; Quality of life data recorded during baseline visit and every 4 weeks for the first 6 months or until treatment discontinuation whichever come first.; Safety: toxicities occurred during treatment period and the fist 30 days from the date of last treatment administration; Compliance endopoints will be recorded during whole treatment period. INCLUSION CRITERIA: 1.Patients affected by pathologically confirmed high‐grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. 2.Relapsed/progressive disease within 6 months from last platinum‐based chemotherapy (platinum resistant/refractory disease) 3.Any line of treatment (after the first). 4.Any “last” chemotherapy line, including Paclitaxel that should have been administered at least 6 months before the study beginning. 5.Patients must be women > 18 years of age. 6.Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: ‐ Haemoglobin = 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomisation ‐ Absolute neutrophil count (ANC) = 1.5 x 109/L ‐ White blood cells (WBC) > 3x109/L ‐ Platelet count = 100 x 109/L ‐ Total bilirubin = 1.5 x institutional upper limit of normal (ULN) ‐ AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper

Euctr, I. T. (2021). "Impact on Disease Relapse of HPV Vaccination in Women Treated With electrosurgical excision with diathermic loop (LEEP) for Cervical Intraepithelial Neoplasia." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: GARDASIL9 0,5 ml ‐ sospensione iniettabile ‐ uso intramuscolare – siringa pre‐riempita (vetro) ‐ 1 siringa preriempita + 2 aghi Product Name: GARDASIL9 0,5 ml ‐ sospensione iniettabile ‐ uso intramuscolare – siringa pre‐riempita (vetro) ‐ 1 s Product Code: [GARDASIL9 0, 5 ml ‐ sospensione iniettabile ‐ uso Pharmaceutical Form: Suspension for injection INN or Proposed INN: Papillomavirus (tipi umani 6,11,16,18,31,33, 45,52,58) Current Sponsor code: Proteina L1 tipi 6,11,16,18,31,33, 45,52,58 di Papillomavirus umano Concentration unit: DF dosage form Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Solvent for parenteral use Route of administration of the placebo: Intramuscular use CONDITION: Prevention of recurrence after a first episode of high‐grade cervical intraepithelial neoplasia (CIN2 +) up to initially invasive cervical cancer (FIGO IA1) ; MedDRA version: 21.1 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000004864 ; MedDRA version: 21.1 Level: LLT Classification code 10056576 Term: Cervical intraepithelial neoplasia System Organ Class: 100000004872 ; MedDRA version: 21.1 Level: PT Classification code 10064328 Term: Human papilloma virus test positive System Organ Class: 10022891 ‐ Investigations Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To evaluate the impact of pre‐surgical HPV 9‐valent vaccination in patients subjected to conization for the management of high‐grade cervical intraepithelial neoplasia (CIN2 +) and initially invasive cervical cancer in terms of possible reduction of recurrent post‐surgical disease. Primary end point(s): ‐ evaluation of the reduction of disease recurrence (cervical intraepithelial neoplasia up to microinvasive cervical cancer) by comparing the number of recurrences in the two arms. Secondary Objective: 1. Analysis of the possible impact of the 9‐valent vaccine on the post‐surgical natural history of HPV infection.; 2. Evaluation of 9‐valent HPV vaccination in patients treated for CIN2 + in terms of possible reduction of the follow‐up scheme in the cervical screening program (investigation on the possible temporal reduction of post‐surgical surveillance). Timepoint(s) of evaluation of this end point: During the entire duration of the study SECONDARY OUTCOME: Secondary end point(s): Analysis of the impact of the vaccine on prevalent post‐surgery infections by comparing the prevalence of persistent HPV infections (duration greater than 12 months after surgery) in the two arms.; Analysis of the impact of the vaccine in the post‐surgical surveillance times, comparison of the viral wash‐out times (negativity of the HPV test), times of negativization of the pap test and of the colposcopic exam in the post‐operative period: comparison of the overexposed times of negativization in the two arms. Timepoint(s) of evaluation of this end point: During the entire duration of the study; During the entire duration of the study INCLUSION CRITERIA: 1. Patients = 18 years old and ecog performance status = 1 2. Patients diagnosed with high‐grade cervical intraepithelial neoplasia or initially invasive cervical cancer (histological findings = CIN2 + and = Ia1 according to the FIGO staging of cervical cancer) 3. No fever at the time of vaccination 4. No previous HPV vaccination 5. Ability to understand and write in Italian 6. Signature of informed consent and consent to personal data Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 1200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Euctr, I. T. (2021). "Metal Allergen Patch Test." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Ammoniated Mercury Product Code: Panel 1 Pharmaceutical Form: Transdermal patch INN or Proposed INN: AMMONIO CLORURO CAS Number: 10124‐48‐8 Current Sponsor code: Pannl 1 Other descriptive name: Dose Range: 0.013, 0.040, 0.12, 0.36 mg/cm² Other Names Ammoniated mercuric chloride, Ammoniated mercury,Hydrargyrum ammoniatum, Hydrargyrum praecipitatum album, Hydrargyrum precipitatum album, Mercuric amidochloride, Mercuric ammonium chloride, Mercuric chloride, ammoniated, Mercury amine chloride, Mercury ammoniated, Mercury ammonium chloride, Mercury(II) chloride ammonobasic, Mercury, ammoniated, Mercury, ammonobasic Quecksilber(II)‐amid‐chlorid, Concentration unit: mg milligram(s) Concentration type: range Concentration number: 0‐0 Route of administration of the placebo: Cutaneous use Product Name: Aluminum chloride hexahydrate Product Code: Panel 2 Pharmaceutical Form: Transdermal patch INN or Proposed INN: ALLUMINIO CLORURO CAS Number: 7784‐13‐6 Current Sponsor code: Panel 2 Other descriptive name: Dose Range: 0.040, 0.12, 0.36, 0.72 mg/cm² Other Names:I3‐01918, Aluminum chloride, Aluminum chloride hexahydrate, Aluminum trichloride hexahydrate, Aluminum(III) chloride, hexahydrate, Concentration unit: mg milligram(s) Concentration type: range Concentration number: 0‐0 Route of administration of the placebo: Cutaneous use Product Name: Aluminum lactate Product Code: Panel 2 Pharmaceutical Form: Transdermal patch INN or Proposed INN: ALLUMINIO LATTATO CAS Number: 18917‐91‐4 Current Sponsor code: Panel 2 Other descriptive name: Dose Range: 0.047, 0.14, 0.42, 0.84 mg/cm² Other Names: Aluminium lactate, Aluminium lacticum, Aluminium‐(RS)‐lactat, Aluminum lactate, Aluminum lactate (Al(O3C3H5)3), Aluminum tris (alpha‐hydroxypropionate), Aluminum, tris (2‐hydro CONDITION: Diagnosis of Allergic Contact Dermatitis ; MedDRA version: 20.0 Level: SOC Classification code 10021428 Term: Immune system disorders System Organ Class: 10021428 ‐ Immune system disorders Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Diagnosis [E01] SECONDARY OUTCOME: Secondary end point(s): ¿ The frequencies (total and by scored character) of late reactions, persistent reactions, and tape irritation will be determined for the entire study population, and by gender and race. The frequencies of late reactions and persistent reactions will also be calculated according to allergen dose tested.; ¿ The frequency of adverse events will be calculated for the entire study population, according to gender and race and to the allergen dose tested.; ¿ Serious adverse events will be described in detailed case reports for each subject.; Timepoint(s) of evaluation of this end point: Late or persistent reactions‐ days 4‐21, tape irritation‐ day 2, adverse and serious events‐ days 2‐21 PRIMARY OUTCOME: Main Objective: To evaluate the diagnostic performance and safety of mercury, aluminum and palladium proposed for inclusion in a T.R.U.E. TEST Metal Patch Test Panel. Primary end point(s): ¿ Determination of optimal test allergen dose as the lowest concentration eliciting either 1+ or 2+ or 3+ positive reaction in 70‐90% of subjects with the fewest number of 3+ reactions;; ¿ Overall concordance and discordance compared to the reference allergen.; ¿ The frequency of ranked skin responses‐ positive (1+, 2+, 3+); negative, doubtful and irritant reactions, will be calculated for each investigational and reference allergen dose tested. Statistical differences between the dose‐related frequencies will be evaluated within each allergen using the Generalized Estimation Equations (GEE) approach, which is based on probability distributions. ; ¿ Skin reaction concordance and discordance between the investigational allergen (mercury, aluminum and palladium) and the corresponding reference allergen will be determined in the total population tested. ; ¿ The frequencies of positive skin reactions to the investigational allergens will be calculated by gender and r e. ; Secondary Objective: No Secondary Objective Timepoint(s) of evaluation of this end point: Day 0‐21 INCLUSION CRITERIA: a. 18 years of age or older. b. History of contact dermatitis; c. Positive patch results to 1) mercury (elemental), 2) aluminum (aluminum chloride hexahydrate, aluminum hydroxide and/or aluminum lactate), 3) palladium (sodium tetrachloropalladate and/or palladium chloride), and/or 4) itching, subcutaneous nodules or excoriated papules at the sites of vaccination injections within the past 10 years; d. Unable to become pregnant or willing to use an acceptable method of contraception to prevent pregnancy if female of childbearing potential; ¿ Inability to become pregnant would include all male subjects and female subjects who are postmenopausal for at least 1 year, or surgically sterile‐ have had a hysterectomy, bilateral ovariectomy, uterine ablation or bilateral tubal ligation. ¿ Acceptable methods of contraception include: 1) systemic birth control; 2) double barrier method (condom with spermicide or diaphragm with spermicide); 3) IUD; 4) vasect

Euctr, I. T. (2021). "A MULTICENTER TRIAL OF A NEW CUSTOMIZED DOSING (RATIONAL ADJUSTMENT OF DOSE TO REDUCE ADVERSE REACTIONS “RADAR” DOSING) OF NIRAPARIB AS MAINTENANCE THERAPY IN PLATINUM SENSITIVE OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL RECURRENT CANCER PATIENTS." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: Niraparib Product Code: [Niraparib] Pharmaceutical Form: Capsule, hard INN or Proposed INN: Niraparib tosilato monoidrato CAS Number: 1038915‐60‐4 Current Sponsor code: na Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Product Name: Niraparib Product Code: [Niraparib] Pharmaceutical Form: Capsule, hard INN or Proposed INN: Niraparib tosilato monoidrato CAS Number: 1038915‐60‐4 Current Sponsor code: na Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ CONDITION: Ovarian, fallopian tube or primary peritoneal recurrent cancer ; MedDRA version: 20.0 Level: LLT Classification code 10006888 Term: Ca ovary System Organ Class: 100000004864 ; MedDRA version: 20.0 Level: LLT Classification code 10006888 Term: Ca ovary System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: The primary objectives of the study are: ; • to compare the safety profile of niraparib RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first three cycles versus the SmPC approved dosing in patients who either have a baseline body weight =58 and <77kg, or have a baseline body weight =77kg and baseline platelet count <150,000/µL (restricted population);; • to evaluate the improvement in the safety profile of niraparib RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first three cycles. Primary end point(s): Rate of patients experiencing a grade =3 thrombocytopenia during the first three cycles. Secondary Objective: • to compare the safety profile of RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first six cycles versus the SmPC approved dosing; • to evaluate the improvement in the safety profile of niraparib RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first six cycles; o to compare the efficacy of niraparib RADAR dosing vs. the SmPC dosing (300 mg); o to compare the safety profile of RADAR dosing compared with the SmPC dosing (300 mg); o to evaluate the safety of niraparib RADAR; • Compliance: to evaluate patients adherence to the two treatment regimens of niraparib (RADAR and SmPC) under study in terms of average administered dose in the first 6 cycles; • Pharmacokinetic: to assess the minimum level of niraparib at the steady state, i.e. trough level concentration and the peak level at two hours after the daily dose Timepoint(s) of evaluation of this end point: During the first three cycles SECONDARY OUTCOME: Secondary end point(s): Rate of patients experiencing a grade =3 thrombocytopenia during the first six cycles; Maximum toxicity grade experienced by each patient, for each toxicity, according to NCI‐CTCAE v. 4.03; Patients experiencing grade 3‐4 toxicities for each toxicity; Type, frequency and nature of SAEs; Patients with at least a SAE; Patients with at least a SADR; Patients with at least a SUSAR; PFS‐6: PFS rate at 6 months, defined as the proportion of patients alive and free from progression at 6 months after randomization.; PFS, defined as the time from the date of treatment randomization to the date of first documentation of progression or death whichever occurs first.; OS at 24 months, defined as the rate of patients who are alive at 24 months from randomization; Pharmacokinetics: Trough level of niraparib concentration at steady state (Css) and peak level at 2 hours after dosing.; Compliance; o Number of administered cycles; o Frequency and reasons for drug discontinuation and treatment modification (suspension, dose reduction).; o Dose intensity Timepoint(s) of evaluation of this end point: During the first six cycles; During the study; During the study; During the study; During the study; During the study; During the study; Six months after randomization; As clinical practice; 24 months from randomization; Cycle 1 at day 1 and 15; cycle 2 and 3 at day 1;c ycle 4 at day 1 and 15 only if dose escalated; on day 1 of any cycle in which the dose s reduced for the first time and on day 1 of the subsequent cycle.; During the study INCLUSION CRITERIA: 1. 18 years of age or older, female, any race 2. Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer 3. High grade (or grade 3) serous histology or known to have gBRCAmut 4. Has received at least 2 previous lines of platinum‐containing therapy (not necessarily consecutive), and has disease that was considered platinum sensitive following the penultimate platinum line (more than 6‐months period between penultimate platinum regimen and progression of disease) 5. Has responded to the last platinum line (PR or CR) 6. No more than 8 weeks have elapsed from completion of the last platinum regimen and the patient is still not progressing after response 7. Eastern Cooperative Oncology Group (ECOG) performance status of = 1 8. Adequate bone marrow, kidney and liver function, defined as follows: a. Absolute neutrophil count = 1,500/µL b. Platelets = 100,000/µL c. Hemoglobin = 9 g/dL d. Serum creatin

Euctr, I. T. (2021). "Olaparib beyond progression compared to platinum chemotherapy after secondary cytoreductive surgery in recurrent ovarian cancer patients. The phase III randomized, open label MITO 35b study: a project of the MITO-MANGO groups." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: CARBOPLATINO Product Code: [CARBOPLATINO] Pharmaceutical Form: Concentrate for solution for infusion CAS Number: 41575‐94‐4 Current Sponsor code: CARBOPLATINO Other descriptive name: CARBOPLATINO Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10‐ Trade Name: LYNPARZA ‐ 100 MG ‐ COMPRESSA RIVESTITA CON FILM ‐ USO ORALE ‐ BLISTER (ALU/ALU) ‐ 56 COMPRESSE Product Name: LYNPARZA Product Code: [LYNPARZA] Pharmaceutical Form: Film‐coated tablet CAS Number: 763113‐22‐0 Current Sponsor code: AZD2281 Other descriptive name: LYNPARZA®, olaparib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Product Name: Cisplatino Product Code: [Cisplatino] Pharmaceutical Form: Concentrate for solution for infusion CAS Number: 15663‐27‐1 Current Sponsor code: Cisplatino Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1‐ Product Name: Gemcitabina Product Code: [Gemcitabina] Pharmaceutical Form: Concentrate for solution for infusion CAS Number: 95058‐81‐4 Current Sponsor code: GEMCITABINA Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 38‐ Product Name: Paclitaxel Product Code: [Paclitaxel] Pharmaceutical Form: Concentrate for solution for infusion CAS Number: 33069‐62‐4 Current Sponsor code: Paclitaxel Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 6‐ Trade Name: LYNPARZA ‐ 150 MG ‐ COMPRESSA RIVESTITA CON FILM ‐ USO ORALE ‐ BLISTER (ALU/ALU) ‐ 56 COMPRESSE Product Name: LYNPARZA Product Code: [LYNPARZA] Pharmaceutical Form: Film‐coated tablet CAS Number: 763113‐22‐0 Current Sponsor code: AZD2281 Other descriptive name: AZD2281, LYNPARZA CONDITION: Recurrent ovarian cancer patients ; MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: • To determine the efficacy (in terms of progression‐free survival) of olaparib maintenance beyond progression when compared to standard chemotherapy in patients with recurrent ovarian cancer undergone secondary cytoreductive surgery for recurrent or progressive disease.; • To determine the efficacy of the experimental therapies on subsequent treatment (in terms of progression‐free survival 2) after progression. Primary end point(s): 1) progression‐free survival; 2) progression‐free survival 2 Secondary Objective: To compare the two arms in terms of: ; ; • Overall Survival; • Safety and tolerability (CTCAE 5.0 version and PRO‐CTCAE questionnaire); • Quality of Life (EORTC QLQ‐C30 questionnaire); • Financial toxicity (PROFFIT questionnaire) Timepoint(s) of evaluation of this end point: Every 12 weeks from C1D1± 7 days SECONDARY OUTCOME: Secondary end point(s): 1) Overall Survival; 2) Safety and tolerability (CTCAE 5.0 version and PRO‐CTCAE questionnaire); 3) Quality of Life (EORTC QLQ‐C30 questionnaire); 4) Financial toxicity (PROFFIT questionnaire Timepoint(s) of evaluation of this end point: 1)time from enrollement to death for any cause; 2) At screening (within 7 days prior to randomization), on Day 1 of each Cycle (during treatment) until 6 months, then at 9 and 12 months, from randomization for both arms or until progression; 2)At screening (within 7 days prior to randomization), on Day 1 of each Cycle (during treatment) until 6 months, then at 9 and 12 months, from randomization for both arms or until progression; 3) At screening (within 7 days prior to randomization), on Day 1 of each Cycle (during treatment) until 6 months, then at 9 and 12 months, from randomization for both arms or until progression INCLUSION CRITERIA: • Signed informed consent prior to any study specific procedures; • Female, age = 18 years at time of signing n ormed consent; • Patients with high‐grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer recurrent or progressive after first line PARPi maintenance are allowed; • Patients must have received only one previous line of a platinum containing regimen not containing bevacizumab; • Patient must have received a first‐line maintenance therapy with a PARPi for at least 6 months; if the prior PARPi used was olaparib then patients must have received treatment without significant toxicity or the need for a permanent dose reduction. Patients who experience disease relapse after the end of the 24 months maintenance therapy are eligible; • Patients must have undergone secondary cytoreductive surgery. The cytoreduction must result in complete resection (absence of macroscopic residual tumor) or at least resection of the

Euctr, I. T. (2021). "A Phase 2 Study of VS-6766 Alone and In Combination with Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (RAMP 201)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Name: ‐‐‐‐‐ Product Code: [VS‐6766] Pharmaceutical Form: Capsule, hard CAS Number: 946128‐90‐1 Current Sponsor code: VS‐6766 Other descriptive name: 3‐[[2‐[(Methylaminosulfonyl)amino]‐3‐fluoropyridin‐4‐yl]methyl]‐4‐methyl‐7‐ [(pyrimidin‐2‐yl)oxy]‐2H‐1‐benzopyran‐2‐one Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 800‐ Product Name: Defactinib Product Code: [VS‐6063] Pharmaceutical Form: Tablet INN or Proposed INN: DEFACTINIB HCl CAS Number: 1073160‐26‐5 Current Sponsor code: VS‐6063 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ CONDITION: Recurrent Low‐Grade Serous Ovarian Cancer (LGSOC) ; MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Part A:; To determine the optimal regimen, either VS‐6766 monotherapy or VS6766 in combination with defactinib, for subsequent evaluation for efficacy in the expansion phase (Part B); Part B:; To determine the efficacy of the optimal regimen identified from Part A Primary end point(s): Part A:; Confirmed overall response rate (ORR; partial response [PR] + complete; response [CR] defined according to RECIST 1.1) as assessed by the blinded independent radiology review committee (BIRC); Part B:; Confirmed ORR defined according to RECIST 1.1 as assessed by the BIRC Secondary Objective: 1) To characterize the safety and toxicity profile of VS‐6766 as a monotherapy and in combination with defactinib in LGSOC; 2); Part A:; To evaluate additional efficacy parameters for VS‐6766 monotherapy; and in combination with defactinib; Part B:; To evaluate additional efficacy parameters for the optimal regimen; identified in Part A; 3) To characterize the pharmacokinetics (PK) of VS‐6766, defactinib, and; relevant metabolites Timepoint(s) of evaluation of this end point: thorough the study SECONDARY OUTCOME: Secondary end point(s): Part A and B:; 1) Adverse events (AEs), serious AEs (SAEs), physical examinations,; clinical laboratory values and tolerability (dose; interruptions/reductions); 2) ; ‐ Duration of response (DOR) as assessed by the BIRC; ‐ ORR as assessed by the Investigator; ‐ Progression free survival (PFS), defined as the time from first dose of; study treatment to the first documentation of PD, or death from any; cause; ‐ Disease control rate (DCR), defined as CR+PR+ stable disease (SD); ‐ Overall survival (OS); 3) PK parameters derived from plasma concentrations of VS‐6766,; defactinib, and relevant metabolites Timepoint(s) of evaluation of this end point: thorough the study INCLUSION CRITERIA: Subjects may be eligible for inclusion in the study if they meet the following criteria: 1. Female subjects >= 18 years of age 2. Histologically proven LGSOC (ovarian, peritoneal) a. The Sponsor's Medical Monitor must review the pathology report prior to the start of treatment b. Adequate pathology material (as defined in the lab manual) must be available prior to enrollment to be used for central confirmation. Central pathological confirmation does not need to be completed prior to enrollment. 3. Tumor with known KRAS mutational status using a validated testing method (blood or tissue) prior to treatment assignment. Adequate archival tumor tissue less than 5 years old or fresh biopsy tissue samples (as defined in the lab manual) must be available for central confirmation prior to treatment assignment. 4. Progression (radiographic or clinical) or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. Below a

Euctr, I. T. (2021). "A phase II trial of short-course versus long-course pre-operative chemotherapy with mFOLFIRINOX or PAXG regimen for stage I-III pancreatic ductal adenocarcinoma (PDAC." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: CISPLATINO SANDOZ ‐ 1 FLAC 100 ML CONCENTRATO PER INFUSIONE 0.5 MG/ML Product Name: Cisplatino Product Code: [15663‐27‐1] Pharmaceutical Form: Concentrate for solution for injection/infusion CAS Number: 15663‐27‐1 Current Sponsor code: ND Concentration unit: mg/ml milligram(s)/millilitre Concentration type: up to Concentration number: 100‐ Trade Name: ABRAXANE ‐ 5 MG/ML ‐ POLVERE PER SOSPENSIONE PER INFUSIONE ‐ USO ENDOVENOSO‐ 100 MG ‐ FLACONCINO(VETRO) 1 FLACONCINO Product Name: abraxane Product Code: [ABI‐007] Pharmaceutical Form: Powder for solution for injection/infusion CAS Number: 33069‐62‐4 Current Sponsor code: ND Other descriptive name: NAB‐PACLITAXEL Concentration unit: mg/ml milligram(s)/millilitre Concentration type: range Concentration number: 3‐12 Trade Name: XELODA ‐ 500 MG 120 COMPRESSE FILMRIVESTITE IN BLISTER USO ORALE Product Name: XELODA Product Code: [154361‐50‐9] Pharmaceutical Form: Tablet CAS Number: 154361‐50‐9 Current Sponsor code: ND Other descriptive name: XELODA Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 500‐ Trade Name: GEMZAR ‐ 200 MG POLVERE PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DA 200 MG Product Name: Gemcitabina Product Code: [95058‐81‐4] Pharmaceutical Form: Concentrate for solution for injection/infusion CAS Number: 95058‐81‐4 Current Sponsor code: ND Other descriptive name: GEMZAR Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Trade Name: IRINOTECAN HOSPIRA ‐ 20MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 100MG/5ML Product Name: irinotecan Product Code: [37037025] Pharmaceutical Form: Concentrate for solution for injection/infusion CAS Number: 100286‐90‐6 Current Sponsor code: ND Other descriptive name: CAM CONDITION: Patients with pancreatic ductal adenocarcinoma ; MedDRA version: 21.0 Level: LLT Classification code 10033602 Term: Pancreatic adenocarcinoma resectable System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: to compare in terms of 1yr‐EFS the efficacy of PAXG to that of mFOLFIRINOX.; to compare in terms of 1yr‐EFS the efficacy of 4 months pre‐operative and 2 months postoperative chemotherapy to that of 6 months of pre‐operative chemotherapy Primary end point(s): EFS,; CA19‐9 failure ; recurrence; ; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. Secondary Objective: OS, RECIST response rate, CA19.9 response rate, and complete pathologic response, resectability rate, surgical mortality and morbidity rate, intra‐ and post‐operative metastasis rate, N0 and R0 resections rate, patients reported outcomes, and treatment toxicity Timepoint(s) of evaluation of this end point: EFS, defined as the time from randomization to: RECIST progression [At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression]; CA19‐9 failure (defined as 2 consecutive increases of serum level =20%, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be. SECONDARY OUTCOME: Secondary end point(s): EFS,; CA19‐9 failure ; recurrence; ; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. Timepoint(s) of evaluation of this end point: EFS, defined as the time from randomization to: RECIST progression [At least a 20% increase in the sum of diameters of target lesions, t ing as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression]; CA19‐9 failure (defined as 2 consecutive increases of serum level =20%, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be. INCLUSION CRITERIA: 1. Cyto/histological diagnosis of pancreatic ductal adenocarcinoma*; 2. Clinical stage I‐III disease according to TNM 8th Ed. 2017 [appendix 1]; 3. Resectable or borderline resectable disease, as anatomically defined according to NCCN Guidelines Version 1.2020 4. Karnofsky Performance Status > 60% [appendix 3]; 5. Age ¿ 18 and = 75 years; 6. Adequate bone marrow function (GB = 3500/mm3, neutrophils =1500/mm3, platelets = 100000/mm3, Hb =10 g/dl); 7. Adequate kidney function (serum creatinine < 1.5 mg/dL); 8. Adequate liver function (ALT and AST < 3 ULN and Serum total bilirubin = 1.5 ULN); 9. No prior treatment (chemotherapy, radiotherapy and/or surgery) for pancreatic cancer; 10. Women must not be on pregnancy or lactation; 11. Patient of child‐bearing potential must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for 4 months after the last study tr

Euctr, I. T. (2021). "Prospective randomized trial comparing corifollitropin alfa (CF-alfa) late start (day 4) vs. CF-alfa standard start (day2) in poor, normal and potential high-responders undergoing IVF/ICSI." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: ELONVA ‐ 150 MCG ‐ SOLUZIONE INIETTABILE ‐ USO SOTTOCUTANEO ‐ SIRINGA PRERIEMPITA(VETRO) ‐ 0.5 ML 1 SIRINGA PRERIEMPITA + 1 AGO Product Name: Elonva Pharmaceutical Form: Solution for injection CONDITION: Therapeutic area: Diseases [C] ‐ Female diseases of the urinary and reproductive systems and pregancy complications [C13] Women with low reproductive capacity ; MedDRA version: 20.0 Level: LLT Classification code 10002658 Term: Anovulation System Organ Class: 100000004860 ; MedDRA version: 20.1 Level: LLT Classification code 10016398 Term: Female infertility System Organ Class: 100000004872 ; MedDRA version: 20.0 Level: LLT Classification code 10071102 Term: Controlled ovarian hyperstimulation System Organ Class: 100000004865 PRIMARY OUTCOME: Main Objective: compare the number of retrieved oocytes in the late start CF‐alfa vs. early start CF‐alfa in patients undergoing IVF Primary end point(s): Number of retrieved oocytes at US guided puncture Secondary Objective: Compare the two protocols with regard to the oocyte morphology (assessed by polarized light microscopy) the rate of clinical pregnancy to six weeks, the incidence of side effects and the degree of satisfaction of the patient Timepoint(s) of evaluation of this end point: 12 months SECONDARY OUTCOME: Secondary end point(s): Pregnancy rate with either applied protocol; Safety and undesired effects of applied protocols Timepoint(s) of evaluation of this end point: 12 months; 12 months INCLUSION CRITERIA: Age 18‐43 years Tubal infertility or male infertility referred for IVF Willingness to undergo randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Euctr, N. L. (2021). "RAINBO: refining Adjuvant treatment IN endometrial cancer Based On molecular features, The MMRD-GREEN trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: IMFINZI Product Name: Durvalumab Pharmaceutical Form: Solution for infusion Pharmaceutical form of the placebo: Infusion Route of administration of the placebo: Intravenous use CONDITION: Endometrial Cancer Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: 3 year recurrence free survival (RFS), in patients with MMRd HREC Primary end point(s): 3 year recurrence free survival.; RFS is defined as time from randomization until date of any recurrence (local or distant) or date of death due to any cause, whichever occurred first.; Secondary Objective: • RFS (median and at 5 years); • OS (median, 3yr, 5yr); • HRQoL; • Safety & tolerability (NCI‐CTC grade 3‐5); • Exploratory translational research (TR), including PD‐L1 testing using SP263 assay and TIP algorithm (>1% and 5%) on biopsy or resections of EC samples.; Timepoint(s) of evaluation of this end point: 3 years SECONDARY OUTCOME: Secondary end point(s): 1. Investigator assessed 5 yr RFS; 2. Overall Survival (OS) (median, 3yr, 5yr): will be determined from the date of registration to the date of death from any cause. Subjects who have not died at the time of the data freeze for the final analysis will be censored at the date the patient was last known to be alive.; 3. HRQoL (EORTC QLQC30 and QLQEN24) ; 4. Safety: Safety and tolerability endpoints will consist of the evaluation of side‐effects according to the NCI‐CTCAE version 5, AEs, withdrawals due to AEs, dose reductions or interruptions.; 5. Immune markers Timepoint(s) of evaluation of this end point: ad 1) at 5 years; ad2) At mortality ; ad 3) at baselinine and months 2,6,12,18, 24 and 36.; ad 4) During theray and till 30 days thereafter; ad 5) between year 3 and 5 INCLUSION CRITERIA: Key inclusion criteria for RAINBO program: • Histologically confirmed diagnosis of EC (all grades and all histologic subtypes, including: including endometrioid, serous endometrial carcinoma, uterine clear cell carcinoma, de‐ /undifferentiated carcinoma, uterine carcinosarcoma). • Molecular classification performed following the diagnostic algorithm described in WHO2020 (adapted from Vermij et al.) • TLH‐BSO or TAH‐BSO with or without lymphadenectomy and/or full surgical staging, without macroscopic residual disease after surgery • No distant metastases as determined by pre‐surgical or post‐surgical imaging (CT scan of chest, abdomen and pelvis or PET‐CT scan) • Written informed consent • Age > 18 years • Patients must be accessible for treatment and follow‐up • Written informed consent according to the local Ethics Committee requirements. Inclusion criteria specific for MMRD‐GREEN Trial: • WHO Performance score 0‐1 • Hist

Euctr, N. L. (2022). "A study investigating the dosing strategy for heated chemotherapy-lavage in the abdominal cavity (hyperthermic intraperitoneal chemotherapy, or HIPEC) during cytoreductive surgery in patients with advanced ovarian cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: Cisplatin Product Name: Cisplatin Product Code: L01XA Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Cisplatin Other descriptive name: NDC 16729‐288 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: up to Concentration number: 100‐ Trade Name: Cisplatin Product Name: Cisplatin Product Code: L01XA Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Cisplatin Other descriptive name: NDC 16729‐288 Concentration unit: mg/l milligram(s)/litre Concentration type: up to Concentration number: 40‐ CONDITION: FIGO stage III high grade serous ovarian cancer, peritoneal cancer, or fallopian tube carcinoma Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To evaluate BSA‐based versus concentration‐based OVHIPEC with cisplatin in patients with advanced‐stage ovarian cancer Secondary Objective: To assess the pharmacokinetics and safety Primary end point(s): The primary endpoint is the platinum concentration in the tumor nodule at the end of the HIPEC procedure. Timepoint(s) of evaluation of this end point: After the cytoreductive surgery plus HIPEC procedure SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints:; ‐ Toxicity evaluation (CTCAE 5.0); ‐ Platinum concentration in normal tissue (in ng/mg wet tissue); ‐ Platinum concentration in tumor tissue after 30 min and 60 min of perfusion (in ng/mg wet tissue); ‐ Concentration versus time curve and AUC of intra‐peritoneal Pt during perfusion; ‐ Cmax, tmax, terminal t ½ in perfusate, clearance from perfusate ate the end of perfusion; ‐ Overall survival (OS) Timepoint(s) of evaluation of this end point: Pharmacokinetic parameters: after the cytoreductive surgery plus HIPEC procedure; Safety: 4‐5 weeks following surgery plus HIPEC INCLUSION CRITERIA: 1. signed and written informed consent 2. age = 18 years 3. patients eligible for interval cytoreductive surgery a. histological proven FIGO stage III primary high grade serous ovarian, fallopian tube, or extra‐ovarian cancer b. when only cytology is performed to confirm the diagnosis ovarian carcinoma, immunohistochemistry should be performed including keratin 7, keratin 20, p53, PAX8 c. neo‐adjuvant chemotherapy consists of (at least) 3 courses of carboplatin/paclitaxel d. following 2 cycles of chemotherapy no progression should occur 4. treated with optimal or complete interval cytoreductive surgery 5. fit for major surgery, WHO performance status 0‐2 6. adequate bone marrow function (hemoglobin level >5.5 mmol/L; leukocytes >3 x 109/L; platelets >100 x 109 /L) 7. adequate hepatic function (ALT, AST and bilirubin <2.5 times upper limit of normal) 8. adequate renal function (creatinine clearance = 60 ml/min using Cockcroft‐

Euctr, P. L. (2022). "Master Protocol of Dato-DXd as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Product Code: AZD5305 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: N/A CAS Number: 2589531‐76‐8 Current Sponsor code: AZD5305 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ Product Name: Durvalumab Product Code: MEDI4736 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Durvalumab CAS Number: 1428935‐60‐7 Current Sponsor code: MEDI4736 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Product Name: Datopotamab deruxtecan Product Code: DS‐1062a Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: Datopotamab deruxtecan CAS Number: 2238831‐60‐0 Current Sponsor code: DS‐1062a Other descriptive name: Anti‐trophoblast cell surface protein 2 (TROP2) antibody‐drug conjugate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Product Name: Capecitabine Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Capecitabine CAS Number: 154361‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Product Name: Flourouracil (5‐FU) Pharmaceutical Form: Solution for injection INN or Proposed INN: fluorouracil CAS Number: 51‐21‐8 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Product Name: Bevacizumab Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Bevacizumab CAS Number: 216974‐75‐3 Current Sponsor code: FKB238 Other descriptive name: A recombinant, humanized IgG1 mAb specific for VEGF Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ Product Name: Carboplatin Pharmaceutical Form: Concen CONDITION: Therapeutic area: Diseases [C] ‐ Cancer [C04] various Advanced/Metastatic solid tumour types ‐ Endometrial Cancer ‐ Gastric Cancer ‐ Ovarian Cancer ‐ Metastatic castration‐resistant prostate cancer ‐ Colorectal cancer ; MedDRA version: 12.0 Level: HLGT Classification code 10007129 Term: Cancer‐related morbidities System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) PRIMARY OUTCOME: Main Objective: ‐To assess the efficacy of Dato‐DXd as monotherapy and in combination with anticancer agents by assessment of ORR; ; ‐To assess the safety and tolerability of Dato‐DXd as monotherapy and in combination with anticancer agents Primary end point(s): ‐ Objective response rate (ORR); ‐ AEs/SAEs, ECOG performance status, changes from baseline in laboratory findings,ECGs, vital signs, physical examinations, and ophthalmologic assessments; ‐ PSA50 response; ‐ Progression‐free survival (PFS) Secondary Objective: ‐ To further assess the efficacy of Dato‐DXd as monotherapy and in combination with anticancer; agents by assessment of PFS, DoR, DCR at 12 and 24 weeks, Best percentage change in tumour size (where applicable); ; ‐ To assess the PK of Dato‐DXd, total anti‐TROP2 antibody, and MAAA‐1181a in plasma; ; ‐ To investigate the immunogenic potential of Dato‐DXd Timepoint(s) of evaluation of this end point: ‐ ORR, PSA50, PFS: data obtained from first dose up until progression per RECIST 1.1 as assessed by the investigator or death, or the last evaluable assessment in the absence of an event (regardless of whether the participant withdraws from therapy); ; ‐ Safety: during the study treatment or the safety follow‐up period (defined as 28 days after last dose of study intervention, or if durvalumab, nivolumab, or bevacizumab is given, 90 days after the last dose will be reported) but prior to subsequent cancer therapy SECONDARY OUTCOME: Secondary end point(s): ‐ Progression‐free survival (PFS); ‐ Duration of response (DoR); ‐ Disease control rate (DCR); ‐ Best percentage change in tumour size; ‐ Overall survival (OS); ‐ Radiographic Progression‐free survival (rPFS); ‐ CA‐125 res nse; ‐ Plasma concentrations and PK parameters, total anti‐TROP2 antibody, and MAAA‐1181a; ‐ Presence of ADAs for Dato‐DXd Timepoint(s) of evaluation of this end point: ‐ PFS, DoR, DCR, Best percentage change in tumour size, rPFS, CA‐125 response: data obtained from first dose up until progression per RECIST 1.1 as assessed by the investigator or death, or the last evaluable assessment in the absence of an event (regardless of whether the participant withdraws from therapy); ‐ OS: data obtained from first dose up until death, or the last evaluable assessment in the absence of an event; ‐ PK and Immunogenicity: blood samples will be taken for specific drugs at limited time points INCLUSION CRITERIA: 1‐ Male and female, = 18 years at the time of screening 2‐Histologically or cytologically documented advanced or metastatic malignancy. 3‐ Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. Archival FFPE tumour samples must be < 12 months old from the time of collection to the time of start of protocol screening. The exception is for gastric Substudy Cohorts 2A and 2B, where prospective PD‐L1 central testing is required for enrolment, archival FFPE tumour samples must be < 6 months old from the time of collection to the time of start of protocol. 4‐ At least 1 lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with CT or MRI and is suitable for accurate repeated measure

Euctr, R. O. (2022). "Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects with Non-small Cell Lung Cancer (NSCLC), Ovarian Cancer, or Breast Cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Trade Name: Nplate Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: ROMIPLOSTIM CAS Number: 267639‐76‐9 Other descriptive name: ROMIPLOSTIM Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Powder for solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: non‐small cell lung cancer (NSCLC), ovarian cancer, or breast cancer ; MedDRA version: 21.1 Level: PT Classification code 10029519 Term: Non‐small cell lung cancer stage III System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non‐small cell lung cancer stage IV System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non‐small cell lung cancer metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10057529 Term: Ovarian cancer metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10070907 Term: Ovarian cancer stage III System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 21.1 Level: PT Classification code 10070908 Term: Ovarian cancer stage IV System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 20.0 Level: PT Classification code 10006201 Term: Breast cancer stage III System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 20.0 Level: PT Classification code 10006202 Term: Breast cancer stage IV System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 20.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] SECONDARY OUTCOME: Timepoint(s) of evaluation of this end point: ‐The primary analysis will be performed at the primary completion date. The primary completion date is defined as the date when the last subject is assessed or receives an intervention for the final collection of data for the primary endpoint for the purposes of conducting the primary analysis, whether the study concluded as planned in the protocol or was terminated early. ; ; ‐When the last subject in the trial completes LTFU at 1 year after the last dose of investigational product, the final database will be locked and unblinded for the final analysis. In the final analysis, the secondary endpoints assessment, and all the exploratory endpoints will be evaluated Secondary end point(s): ‐ the depth of the platelet count nadir from the start of the first on‐study chemotherapy cycle through the end of the treatment period ; ‐the time to first platelet response, defined by platelet count 100 x 109/L in the absence of platelet transfusions during the preceding 7 days ; ‐the duration‐adjusted event rate of grade 2 bleeding events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading scale ; ‐overall survival ; ‐platelet transfusion(s) during the treatment period PRIMARY OUTCOME: Main Objective: to evaluate the efficacy of romiplostim for the treatment of CIT in patients receiving chemotherapy for the treatment of NSCLC, ovarian cancer, or breast cancer measured by the ability to administer on‐time, full‐dose chemotherapy Timepoint(s) of evaluation of this end point: ‐The primary analysis will be performed at the primary completion date. The primary completion date is defined as the date when the last subject s assessed or receives an intervention for the final collection of data for the primary endpoint for the purposes of conducting the primary analysis, whether the study concluded as planned in the protocol or was terminated early. Primary end point(s): no thrombocytopenia‐induced modification of any myelosuppressive agent in the second and third cycles of the planned on‐study chemotherapy regimen. Thrombocytopenia‐induced; modifications include chemotherapy dose reduction, delay, omission, or chemotherapy treatment discontinuation due to platelet counts below 100 x 109/L. Secondary Objective: ‐to compare the treatment effect of romiplostim with that of placebo on the depth of platelet nadir; ‐to compare the treatment effect of romiplostim with that of placebo on the time to first platelet response; ‐to compare the treatment effect of romiplostim with that of placebo on the incidence of > grade 2 bleeding events; ‐to compare the treatment effect of romiplostim with that of placebo on overall survival; ‐to compare the treatment effect of romiplostim with that of placebo on the incidence of platelet transfusions; ‐to compare the treatment effect of romiplostim with that of placebo on the proportion of patients achieving platelet response; ‐overall safety of romiplostim ; ‐achieving a platelet count 100 x 109/L at any time after study day 1 to week 4 (i.e. 7 days after the planned third dose of investigational product) and in the absence of platelet transfusions during the preceding 7 days ; ‐adverse events, including treatment‐emergent adverse events, fatal ; adverse events, serious adverse events,and clinically significant changes in laboratory values ; ‐anti‐romiplostim antibodies and antibodies to thrombopoietin (TPO) ; ‐myelodysplastic syndromes and secondary malignancies INCLUSION CRITERIA: 1. Subject has provided informed consent prior to initiation of any study‐specific activities/procedures or subject’s legally acceptable representative has provided informed consent prior to any study‐specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent. 2. Males or females > 18 years of age at signing of the informed consent. 3. Documented active stage III or IV locally advanced or metastatic NSCLC, breast cancer, or ovarian cancer, or any stage recurrent disease. •patients with documented locally advanced (stage III) NSCLC should not be amenable to definitive treatment with chemoradiation and/or surgery. 4. Subjects must be receiving cancer treatment with 21‐ or 28‐day cycles, using one of the following carboplatinum‐based combination chemotherapy regimens: carboplatin/gemcitabine based, carbo

Eugonia (2022). Value of Follicular Flushing. Randomised Controlled Trial.
	No Results Available Procedure: Experimental: Follicular aspiration with addition of follicular flushing. Number of oocytes retrieved|Oocyte recovery rate|Oocyte maturation rate|Fertilization rate|Percentage of good quality embryos on day 2/3 Female Not Applicable 105 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Flushing RCT December 31, 2022

Eun, T., et al. (2023). "Therapeutic outcome of folate receptor alpha targeting antibody-drug conjugates in relapsed ovarian cancer: a meta-analysis."
	
Evangelia, K., et al. (2024). "Effect of autologous platelet-rich plasma on women undergoing IVF with a history of three unsuccessful embryo transfers under the age of 35, four unsuccessful embryo transfers between the ages of 35 and 39, or six unsuccessful embryo transfers at the age of 40 and above: a systematic review and meta-analysis."
	
Evangelia, K., et al. (2024). "Effect of intrauterine infusion of autologous platelet-rich plasma on women with repeated implantation failure undergoing IVF: a systematic review and meta-analysis."
	
Evans, D. (2021). "Regarding "Optimal Dose of Pituitrin in Laparoscopic Uterine Myomectomy: a Prospective, Double-Blinded, Randomized Controlled Trial"." Journal of Minimally Invasive Gynecology 28(11): 1956.
	
Evans, K., et al. (2022). "Remotely Delivered Interventions to Support Women With Symptoms of Anxiety in Pregnancy: Mixed Methods Systematic Review and Meta-analysis." Journal of Medical Internet Research 24(2): e28093.
	BACKGROUND: Symptoms of anxiety are common in pregnancy, with severe symptoms associated with negative outcomes for women and babies. Low-level psychological therapy is recommended for women with mild to moderate anxiety, with the aim of preventing an escalation of symptoms and providing coping strategies. Remotely delivered interventions have been suggested to improve access to treatment and support and provide a cost-effective, flexible, and timely solution. OBJECTIVE: This study identifies and evaluates remotely delivered, digital, or web-based interventions to support women with symptoms of anxiety during pregnancy. METHODS: This mixed methods systematic review followed a convergent segregated approach to synthesize qualitative and quantitative data. The ACM Digital Library, Allied and Complementary Medicine Database, Applied Social Sciences Index and Abstracts, Centre for Reviews and Dissemination database, the Cochrane Central Register of Controlled Trials, the Cochrane Library, CINAHL, Embase, Health Technology Assessment Library, IEEE Xplore, Joanna Briggs Institute, Maternity and Infant Care, MEDLINE, PsycINFO, and the Social Science Citation Index were searched in October 2020. Quantitative or qualitative primary research that included pregnant women and evaluated remotely delivered interventions reporting measures of anxiety, fear, stress, distress, women's views, and opinions were included. RESULTS: Overall, 3 qualitative studies and 14 quantitative studies were included. Populations included a general antenatal population and pregnant women having anxiety and depression, fear of childbirth, insomnia, and preterm labor. Interventions included cognitive behavioral therapy, problem solving, mindfulness, and educational designs. Most interventions were delivered via web-based platforms, and 62% (8/13) included direct contact from trained therapists or coaches. A meta-analysis of the quantitative data found internet-based cognitive behavioral therapy and facilitated interventions showed a beneficial effect in relation to the reduction of anxiety scores (standardized mean difference -0.49, 95% CI -0.75 to -0.22; standardized mean difference -0.48, 95% CI -0.75 to -0.22). Due to limitations in the amount of available data and study quality, the findings should be interpreted with caution. Synthesized findings found some evidence to suggest that interventions are more effective when women maintain regular participation which may be enhanced by providing regular contact with therapists or peer support, appropriate targeting of interventions involving components of relaxation and cognitive-based skills, and providing sufficient sessions to develop new skills without being too time consuming. CONCLUSIONS: There is limited evidence to suggest that women who are pregnant may benefit from remotely delivered interventions. Components of interventions that may improve the effectiveness and acceptability of remotely delivered interventions included providing web-based contact with a therapist, health care professional, or peer community. Women may be more motivated to complete interventions that are perceived as relevant or tailored to their needs. Remote interventions may also provide women with greater anonymity to help them feel more confident in disclosing their symptoms.

Evans, S. K. L., et al. (2021). "A Novel Injection Technique for Extended-Release Local Anesthetic After Posterior Colporrhaphy and Perineorrhaphy: a Randomized Controlled Study." Female Pelvic Medicine & Reconstructive Surgery 27(6): 344‐350.
	OBJECTIVES: To evaluate the effect of vaginal intraoperative infiltration of liposomal bupivacaine on vaginal pain among patients undergoing posterior colporrhaphy and perineorrhaphy. METHODS: This was a randomized, placebo‐controlled trial offered to women undergoing posterior colporrhaphy and perineorrhaphy with concomitant pelvic reconstructive procedures. Liposomal bupivacaine or normal saline placebo (30 mL) was injected into the posterior vaginal compartment and perineal body in 2‐ to 3‐mL increments, using a systematic technique. All participants received 10‐mL 0.25% bupivacaine with epinephrine prior to incision. Perioperative care was standardized. The primary outcome was vaginal pain as measured by a visual analog scale. RESULTS: One hundred twenty‐six women were screened, and 72 were included. Demographic characteristics were similar. Median visual analog scale was not different at any time point (P = 0.81). There were no differences in secondary outcomes, including narcotic use (37.5 vs 37.5 mg morphine equivalents, P = 0.51; placebo vs liposomal bupivacaine), time to first opioid (68 vs 89.5 minutes, P = 0.56), antiemetic doses (3 vs 2, P = 0.07), hospital length of stay (24 vs 21.9 hours, P = 0.98), length of stay in postanesthesia care unit (93 vs 100 minutes, P = 0.32), proportion of patients who had a bowel movement within the first 3 postoperative days (65.7 vs 59.5% P = 0.36), or successful voiding trials (45.7 vs 59.5%, P = 0.24). There were no differences in patient satisfaction or postoperative adverse events. CONCLUSIONS: In this study of pelvic reconstructive surgeries with posterior colporrhaphy and perineorrhaphy, there were no differences in pain scores or any secondary outcomes between liposomal bupivacaine and placebo injected into the posterior vaginal compartment.

Evelyne, R., et al. (2021). "The Effect of Post-Operative Suppressive Treatment on the Fertility Prognosis of Women with Endometriosis: a Systematic Review and Meta-Analysis."
	
Everhoj, C., et al. (2022). "Effects of early maternal cancer and fertility treatment on the risk of adverse birth outcomes." EClinicalMedicine 46: 101369.
	Background: Early maternal cancer and fertility treatment each increase the risk for adverse birth outcomes, but the joint effect of these outcomes has not yet been reported. Thus, the aim was to assess the individual and joint effect of maternal cancer and fertility treatment on the risk for adverse birth outcomes. Method(s): This population-based cohort study included 5487 live-born singletons identified in the Danish Medical Birth Register (1994-2016) of mothers with previous cancer (<40 years) recorded in the Danish Cancer Registry (1955-2014). We randomly selected 80,262 live-born singletons of mothers with no cancer <40 years matched to mothers with cancer by birth year and month. We calculated odds ratios (ORs) for preterm birth, low birth weight (LBW) (<2500 g) and small for gestational age (SGA), mean differences in birth weight in grams, and additional cases of preterm birth (gestational age<259 days) per 100,000 person-years. Multiplicative and additive interaction of maternal cancer and fertility treatment was compared with outcomes of children conceived naturally to mothers with no maternal cancer (reference group). Finding(s): Among 84,332 live-born singletons, increased ORs for preterm birth were observed among children born to mothers with previous cancer (1.48, 95% confidence interval [CI] 1.33-1.65) or after fertility treatment (1.43, 95% 1.28-1-61), with 22 additional cases of preterm birth among both group of children (95% CI 15-29; 95% CI 14-30). In the joint analyses, the OR for SGA for children born after fertility treatment to mothers with previous cancer was similar to that of the reference group (OR 1.02, 95% CI 0.72-1.44, P for interaction=0.52). Children with both exposures had increased ORs for LBW (1.86, 95% CI 1.17-2.96, P for interaction=0.06) and preterm birth (2.31, 955 CI 1.66-3.20, P for interaction = 0.56), with 61 additional cases of preterm birth (95% CI 27-95, P for interaction=0.26) over that of children in the reference group. The mean birth weight was also lower in children born to mothers with both exposures (-140 g, 95% CI -215; -65) (P for interaction=0.06) but decreased to -22 g (95% CI -76; 31) after adjustment for GA. Interpretation(s): Although we did not find any statistically significant additive interaction between maternal cancer and fertility treatment, children born after fertility treatment of mothers with previous cancer were at increased risk for adverse birth outcomes. Thus, pregnant women with both exposures need close follow-up during pregnancy. Funding(s): The Danish Cancer Society and the Danish Childhood Cancer Foundation.Copyright © 2022 The Author(s)

evgeniya, s. and I. Sapiyat (2023). "The value of cell-based therapy in women with thin endometrium and Asherman syndrome: systematic review."
	
Ewerton, F., et al. (2023). "Efficacy and Safety of Eliapixant in Overactive Bladder: The 12-Week, Randomised, Placebo-controlled Phase 2a OVADER Study." European Urology Focus.
	Background: Effective, well-tolerated novel treatments for overactive bladder (OAB) are lacking. The P2X3 receptor antagonist eliapixant demonstrated potential to reduce OAB symptoms in preclinical studies. Objective(s): To evaluate the safety, tolerability, and efficacy of eliapixant in patients with OAB with urgency urinary incontinence (UUI). Design, setting and participants: OVADER was a 12-wk, randomised, placebo-controlled, double-blind, parallel-group, multicentre, phase 2a study (NCT04545580) conducted between 2020 and 2022 in private and institutional clinical practices. Eligible patients were aged >=18 yr with wet OAB symptoms (urgency, urinary frequency, and urinary incontinence) for >=3 mo before screening. Intervention(s): Randomisation (1:1 ratio) to oral eliapixant 125 mg or placebo twice daily. Outcome measurements and statistical analysis: The primary endpoint was the mean change from baseline in the mean number of UUI episodes/24 h over weeks 4, 8, and 12 according to an electronic bladder diary, evaluated using a repeated-measurement model in a Bayesian framework. Results and limitations: Of 202 patients enrolled, 85 were valid for per-protocol analysis. The primary efficacy endpoint was not met. The posterior probability for eliapixant superiority over placebo was 40% (point estimate 0.05, 95% credible interval - to 0.38), which did not meet the predefined criterion of >=90% probability. Secondary and exploratory endpoints were not met. The incidence of adverse events was similar in the eliapixant (n = 32, 63%) and placebo (n = 27, 56%) groups; most were mild and five led to discontinuation of eliapixant. Conclusion(s): OVADER did not meet its clinical efficacy endpoints. Potential reasons include the nonspecific OAB symptom complex, the poorly understood pathophysiology, and the coinciding COVID-19 pandemic. Patient Summary: We tested whether a new drug called eliapixant would reduce symptoms of overactive bladder in comparison to placebo. We found that the drug did not work. More knowledge on how overactive bladder occurs is needed to find new drugs to treat this condition.Copyright © 2023

Eyck, B., et al. (2022). "OUTCOME OF NEOADJUVANT CHEMORADIOTHERAPY PLUS SURGERY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN EAST ASIA VERSUS WESTERN EUROPE." Diseases of the Esophagus 35(Supplement 2): 106.
	Patients with different ethnic and genetic backgrounds may respond differently to specific anticancer therapies. The present study aimed to assess whether patients with esophageal squamous cell carcinoma (ESCC) who are treated with neoadjuvant chemoradiotherapy (nCRT) according to the CROSS regimen in East Asia have an inferior response compared to patients treated in Western Europe. Patients with ESCC who completed >=80% of nCRT according to CROSS (five weekly cycles of carboplatin [AUC of 2 mg/mL/min] and paclitaxel [50 mg/m2] with concurrent 41.4 Gy radiotherapy in 23 daily fractions of 1.8 Gy) followed by esophagectomy between June 2012 and April 2020 were identified from Asian and Dutch databases. Primary endpoint was pathologically complete response (pCR), defined as ypT0N0. Asian and Dutch patients were compared with nearest-neighbor propensity score matching, adjusting for confounding factors: gender, Charlson comorbidity index, tumor location, cT and cN stage, interval from start of nCRT to surgery, and number of resected lymph nodes. In total, 839 patients were included (Asian: 175, Dutch: 664). After matching, 154 remained in each group. Confounding factors were all significantly different before matching and 26% in the Asian versus 42% in the Dutch cohort had a pCR (p<0.001), which became 27% versus 42% after matching (p=0.008), respectively. Both ypT and ypN stage were significantly higher in the Asian cohort. R0 resection rate was comparable (Asian: 92% vs. Dutch: 95% resp., p=0.29). Asian patients more often had a cervical anastomosis (p=0.001) and less complications including pulmonary complications (21%- 38%, p=0.002), chyle leakage (2%-10%, p=0.006) and anastomotic leakage (10%-21% resp., p=0.02). The present study shows that after adjusting for patient and tumor characteristics, East Asian patients with ESCC have a poorer response to nCRT according to the CROSS regimen than Western European patients. The poorer response did not seem to have a negative effect on surgical outcome. Future studies investigating anticancer therapy for esophageal cancer should take into account ethnic and genetic differences in response to these regimens.

Ezzat, R. S., et al. (2021). "Impact of bariatric surgery on androgen profile and ovarian volume in obese polycystic ovary syndrome patients with infertility." Saudi journal of biological sciences 28(9): 5048-5052.
	Obesity has major adverse effects on reproductive performance and fertility potential especially in women with polycystic ovary syndrome. In this study, we aimed to evaluate the consequences of excess weight reduction by bariatric surgery on androgen levels, and ovarian volume by ultrasonography in obese polycystic ovary patients. This one year Cohort study was carried out in Zagazig university hospitals. The study included 36 infertile women with PCOS and obesity, who underwent bariatric surgery(sleeve gastrectomy or gastric bypass). Patients were evaluated for free and total serum testosterone levels, Sex hormone binding globulin (SHBG), free androgen index (FAI) and also ovarian volume by ultrasound pre-operatively, 6 months and 1 year after surgery. The results showed significant reduction in Body Mass Index, free and total serum testosterone levels and rise in SHBG and regulation of menstrual cycle at 6 and 12 months after operation. Free androgen index and ovarian volume by ultrasound also significantly decreased (p < 0.001) .As a conclusion, Bariatric surgery results in durable loss of weight and restores the normal physiological balance of androgenic milieu and ovarian morphology by ultrasound, in infertile women who have Polycystic ovary syndrome.

f2fgkn, R. B. R. (2023). "Comparison of the application of Current Therapy to the unilateral versus bilateral tibial nerve in women with Urine Leakage." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This is a randomized, controlled, two‐arm, parallel, blinded clinical trial. Women who meet the inclusion criteria and do not meet the exclusion criteria will be randomized into 2 groups. The randomization sequence will be generated using a computer‐based randomization program in blocks of 10. The randomization group will be placed in opaque envelopes. The investigator responsible for the initial assessment will allocate women to the randomized group following a recruitment order. Women will be blind as to which group they will belong to: Unilateral Tibial Group or Bilateral Tibial Group. Unilateral group (G1) will consist of 50 participants diagnosed with overactive bladder syndrome or mixed urinary incontinence with predominance of urinary urgency, which will indicate the intervention to apply transcutaneous electrical stimulation in the region of the tibial nerve in the left lower limb, but will have the patient apply to both limbs to maintain blinding. The women will be isolated to 1 initial evaluation + 12 sessions of electrostimulation application (frequency twice a week, totaling 12 weeks and duration of 30 minutes each session), using the DualPe X961 TENS device with the following parameters: pulse width of 200µs, 1Hz frequency to find the motor point and increase the intensity as needed, finally, increase the frequency to 10Hz + 1 final assessment and reassessment at 1, 3 and 6 months for follow‐up. Bilateral group (G2): 50 participants diagnosed with overactive bladder syndrome or mixed urinary incontinence with predominance of urinary urgency, awaiting the application of transcutaneous electrical stimulation in the region of the tibial nerve in the left and right lower limbs, which will be attended to 1 evaluation initial + 12 sessions of electrostimulation a CONDITION: C12.050.351 Overactive Urinary Bladder; Urinary Incontinence PRIMARY OUTCOME: Expected outcome 1: improvement in urinary symptoms in both groups, but greater in the bilateral group. Urinary symptoms will be assessed using questionnaires validated for Portuguese (QUID, ICIQ‐SF and OAB), voiding diary carried out before and after the 12 intervention sessions and subjective report of the woman (question with LIKERT scale) INCLUSION CRITERIA: Women aged 18 or over; diagnosed with overactive bladder syndrome or mixed urinary incontinence with predominance of urgency; women who voluntarily accept the informed consent form (ICF); know how to read and write SECONDARY OUTCOME: Impact on sleep quality. We expect improvement in sleep quality in both groups, but higher in the bilateral group. Sleep quality will be assessed with a questionnaire validated for Portuguese (Patient‐Reported Outcomes Measurement Information System (PROMIS) Impact on symptoms of anxiety and depression. We expect improvement in psychological symptoms in both groups, but greater in the bilateral group. Psychological symptoms will be evaluated with a questionnaire validated for Portuguese (DASS‐21) Improvement in quality of life. We expect improvement in both groups, but greater in the bilateral group. Quality of life will be assessed using questionnaires validated for Portuguese (Incontinence Quality of life Questionnaire (I‐QOL) Improvement in sexual função. We expect improvement in both groups, but greater in the bilateral group. Sexual function will be assessed using a questionnairevalidated for Portuguese (FSFI)

Fabbi, M., et al. (2022). "Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab." Diagnostics (Basel, Switzerland) 12(9).
	To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan-Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.

Fabbro, M., et al. (2022). "EE493 Cost-Effectiveness of Pembrolizumab+Lenvatinib for Treatment of Advanced Endometrial Carcinoma in Women Who Have Progressed Following Prior Systematic Therapy and Are Not Candidates for Curative Surgery or Radiation in France." Value in Health 25(12 Supplement): S152-S153.
	Objectives: To evaluate cost-effectiveness of pembrolizumab plus lenvatinib for treatment of advanced endometrial carcinoma in women who have progressed following prior systematic therapy and are not candidate for curative surgery or radiation, from the French healthcare system perspective. Method(s): A three-state partitioned survival model (pre-progression, post-progression and death) was developed to estimate costs, effectiveness, and incremental cost-effectiveness ratio (ICER) of pembrolizumab + lenvatinib versus chemotherapy (doxorubicin or paclitaxel). Clinical and quality of life data were derived from the phase 3 study KEYNOTE-775. Progression-free survival, overall survival and time on treatment were extrapolated over a 10-year time horizon based on parametric functions. EQ-5D-5L data estimated by a regression model were converted to French population-based utilities using the French value set. Only direct medical costs were considered, based on public sources. Costs and health outcomes were discounted at 2.5% per year. ICER was calculated as cost per quality-adjusted life year (QALY) gained and per life year gained (LYG). Deterministic and probabilistic sensitivity analyses and scenarios analyses were conducted to assess robustness of results. Result(s): The model projected that pembrolizumab + lenvatinib is associated with 1.25 LYG and 1.04 additional QALY versus chemotherapy as well as incremental costs of 131,293 (discounted). ICERs were 126 246/QALY and 104 607/LY respectively. Results were mostly sensitive to parametric survival functions chosen to extrapolate overall survival, with an ICER varying from 107 532/QALY (-15%) with Log-normal to 144 565/QALY (+14%) with Weibull. Pembrolizumab plus lenvatinib has more than 80% probability of being cost-effective beyond the willingness-to-pay (WTP) threshold of 160,000/QALY. Conclusion(s): Model-based analysis suggests that pembrolizumab + lenvatinib improves life expectancy and is likely to be cost-effective versus chemotherapy for treatment of advanced endometrial carcinoma in women who have progressed following prior systematic therapy and are not candidate for curative surgery or radiation in France, assuming a WTP under 160,000/QALY.Copyright © 2022

Faber, M. A., et al. (2021). "Transobturator Versus Single-Incision Sling for Predominant Stress Urinary Incontinent (SUI) Women: a Randomized Controlled Trial." Journal of Minimally Invasive Gynecology 28(11): S153.
	Study Objective: To assess whether single‐incision sling (SIS) is non‐inferior to transobturator (TOT) sling regarding efficacy for treating women with confirmed stress‐predominant urinary incontinence (SUI). Design: Prospective, parallel, non‐blinded, multicenter, randomized controlled study. Setting: Two tertiary, academic hospitals. Patients or Participants: Ninety‐nine patients were followed 6 and 12 months after surgery. Interventions: Mid‐urethral TOT sling (Obtryx II® – Halo; n=50) with regional anesthesia or SIS (Solyx®; n=49) with local anesthesia. Intention‐to‐treat analysis was performed. Measurements and Main Results: The primary outcome was improvement in the Patient Global Improvement (PGI‐I) and Kings Health Questionnaire (KHQ) instruments after treatment. Secondary outcomes were subjective improvement (improved/cured), number of reoperations, estimated blood loss (EBL), operative room (OR) time, post‐op complications. Both groups were homogeneous (p=NS) regarding age(p=0.728), race(p=0.112), body mass index(p=0.082), menopausal status(p=0.359), vaginal deliveries(p=0.839), tobacco use(p=0.385) and sexual activity(p=0.605). There was no difference in the PGI after 6(p=0.067) and 12 months(p=0.128) of treatment between the groups. KHQ scores were better improved in the TOT group for the following domains: role limitations(p=0.049), physical limitations(p=0.0105) and severity measures(p=0.0416). The other domains (general health, incontinence impact, personal relationships, emotions, sleep/energy) were not different between the groups. After 12 months, TOT group was only superior to SIS in the general health domain(p=0.0189). However, the TOT group presented higher subjective improvement after 6 months (93.62 vs 75%; p=0.013) than SIS group, with no significant difference after 12 months. Six patients from the SIS group were reoperated versus three from the TOT group(p=0.309). The SIS group presented a smaller EBL (17.95 vs 33.9 ml; p=<0.005) and shorter OR time (16 vs 40.3 min; p<0.005) than the TOT group. Erosion rate was higher in the SIS group(p=0.059). No major complications occurred in both groups. Conclusion: TOT and SIS groups were equally effective after 6 and 12 months after treatment according to the PGI‐I and KHQ instruments. Subjective improvement was higher in the TOT group after 6 months, with no difference after 12 months.

Fabi, A., et al. (2022). "The immersive experience of virtual reality during chemotherapy in patients with early breast and ovarian cancers: The patient's dream study." Frontiers in Oncology 12: 960387.
	Background: A virtual reality experience (VRE) could represent a viable non-pharmacological intervention to reduce and better manage the main factors of psychophysical distress related to the diagnosis and treatment of cancer.; Aim: The "Patient's Dream" study was a two-arm randomized controlled trial conducted at the Regina Elena National Cancer Institute - IRCCS (Rome, Italy) from April 2019 to January 2020 to evaluate VRE impact in patients affected by breast or ovarian cancer. Before starting the first cycle of chemotherapy (CT), patients were randomized to receive the VRE (VRE arm) as "distraction therapy" or to entertain themselves with conventional means (control arm). The primary aims were the assessment of psychological distress, anxiety and quality of life between the two study arms. Secondary endpoints were the perceived time during the first course of CT and the acute and late toxicity.; Results: Fourty-four patients were enrolled, 22 patients were randomly assigned to the VRE arm and 22 to the control arm. Collected data underline the absence of prevalent disturbs of anxiety and depression in both groups. Nevertheless, even if the state anxiety values before and after CT decreased in both groups, this reduction was statistically significant over time only in the VRE arm. The duration of therapy perceived by patients undergoing distraction therapy was significantly shorter when compared to the control group. The use of VRE during the first CT cycle appeared to reduce asthenia outcomes.; Conclusion: Obtained data suggest that the VRE positively influenced the levels of state anxiety among cancer patients and support the continuous research on VRE as a distraction intervention, with the aim to meet the clinical need for effective nonpharmacologic adjunctive therapies.; Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05234996, identifier NCT05234996.; Competing Interests: Authors FG, AG and GG are funders of Twiceout. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Fabi, Fotia, Giuseppini, Gaeta, Falcicchio, Giuliani, Savarese, Taraborelli, Rossi, Malaguti, Giannarelli, Pugliese and Cognetti.)

Fabiana, C. and P. Veronique (2022). "Impact of endometriosis surgery on Lower Urinary Tract."
	
Fabiani, C., et al. (2022). "Female fertility preservation: Impact of cancer on ovarian function and oocyte quality." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 156(1): 166-171.
	Objective: To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH).; Methods: This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0.; Results: Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P < 0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself.; Conclusion: Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation. (© 2021 International Federation of Gynecology and Obstetrics.)

Fabio, B. and F. Simone (2021). "A systematic review on the clinical use of indocyanine green in Endometriosis Surgery."
	
Fachini, A. M. D., et al. (2021). "Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial." Gynecologic Oncology 160(2): 379-383.
	OBJECTIVE: The present analysis determined the disease free survival (DFS) and overall survival (OS) at up to 14 years of follow-up in women who participated in our previous phase 3 randomized controlled clinical trial, in which women with stage IIIB squamous cervical cancer received either cisplatin plus RT or RT alone for treatment. The first study showed that the addition of cisplatin to RT offered a significant benefit in DFS, but not in OS. METHODS: The present analysis examined DFS and OS in 146 women from the original cohort (72 patients in the CRT arm and 74 patients in the RT-only arm) with follow-up of up to 14 years. RESULTS: Longer term follow-up showed that treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only. Patients who received RT alone had significantly worse OS (HR, 1.88; 95% CI, 1.09-3.24) and DFS (HR, 1.82; 95% CI, 1.07-3.08) compared with patients who received CRT. The multivariate analyses also showed that the patients with baseline Karnofsky performance status (KPS) <90% showed significantly worse OS (HR, 3.11; 95% CI, 1.78-5.43), as did those with hemoglobin <10 mg/dL (HR, 4.32; 95% CI, 2.23-8.36). Patients with baseline KPS < 90% showed significantly worse DFS (HR, 2.83; 95% CI, 1.60-5.01), as did those with hemoglobin <10 mg/dL (HR, 4.16; 95% CI, 2.17-7.95). CONCLUSIONS: For stage IIIB cervical cancer, treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only.

Factor, P. A. and K. Pasamba (2023). "METFORMIN AS AN ADJUNCT TO PROGESTIN THERAPY IN ENDOMETRIAL HYPERPLASIA AND EARLY-STAGE ENDOMETRIAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS." International Journal of Gynecological Cancer 33(Supplement 4): A52.
	Introduction Metformin has been studied for its anti-proliferative effects in endometrial cells, and it is hypothesized to have a synergistic effect with progestin therapy in suppressing endometrial cell proliferation. This systematic review and metaanalysis aimed to determine the efficacy of adjunctive metformin in the clinical regression of endometrial hyperplasia and early-stage endometrial carcinoma. Methods This meta-analysis followed the Cochrane methodology and adhered to the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) were included if they enrolled reproductive-aged women with endometrial hyperplasia (with and without atypia) and endometrial carcinoma who were treated with progestin and metformin. The primary outcome was the complete response rate at 12-16 weeks, and secondary outcomes included relapse rate, clinical pregnancy rate, and live birth rate. Odds ratios (ORs) and 95% confidence intervals (CIs) were used for dichotomous data. Results Six RCTs were included. The addition of metformin to progestin therapy may increase the complete response rate of endometrial hyperplasia without atypia (OR 5.12, 95% CI 1.17 to 22.41; n=102) and live birth rates (OR 2.51, 95% CI 1.34 to 4.69; n=188) compared to progestin therapy alone, but the certainty of the evidence is low. Metformin did not have a significant effect on the clinical response of endometrial hyperplasia with atypia and endometrial carcinoma, relapse rates, and clinical pregnancy rates. Conclusion/Implications Current evidence is uncertain on the potential benefit of metformin with progestin in endometrial hyperplasia and carcinoma. Future high-quality randomized controlled trials with larger sample sizes and longer follow-up periods are needed to support practice recommendations.

Fader, A. N., et al. (2021). "A randomized phase III, two-arm trial of paclitaxel, carboplatin, and maintenance letrozole versus letrozole monotherapy in patients with stage II-IV, primary low-grade serous carcinoma of the ovary or peritoneum." Journal of Clinical Oncology 39(15 SUPPL).
	Background: Low‐grade serous carcinoma of the ovary or peritoneum (LGSOC) is a rare subtype of epithelial carcinoma. Differences in epidemiology, pathogenesis, disease presentation, and clinical outcomes have been characterized between women diagnosed with LGSOC and those with the p53‐driven highgrade serous carcinoma (HGSOC). Ultimately, patients with LGSOC should be treated differently than those with HGSOC. Several studies suggest that LGSOC is relatively chemoresistant and that most tumors robustly express estrogen and progesterone receptors. Recently, retrospective reports suggest that utilization of the aromatase inhibitor, letrozole, as monotherapy or in addition to platinum/taxane‐based chemotherapy in those with primary advanced‐stage LGSOC results in preliminarily promising survival outcomes. Methods: This study is a two‐arm, randomized, open‐label, Phase III clinical trial. The primary objective is to assess whether letrozole monotherapy (2.5 mg po daily) is non‐inferior to carboplatin (AUC 5‐6) and paclitaxel (175 mg/m2 ) followed by letrozole maintenance therapy with respect to progression free survival in women with primary, Stage II‐IV LGSOC who have undergone an attempt at maximal surgical cytoreduction. Secondary endpoints include incidence of adverse events, objective response rate in those with measurable disease after surgery, response duration, overall survival, and adherence to letrozole maintenance therapy. Study subjects must have undergone a bilateral salpingooophorectomy, and p53 IHC testing of tumors is required to rule out those with aberrant p53 expression commonly observed in HGSOC tumors. Study strata include residual disease status and country of enrollment. Four hundred and fifty patients will be enrolled in the United States, Canada and South Korea through the NRG Oncology trials network. Correlative aims include analyzing the association of ER/PR tumoral expression with aromatase inhibitor therapy response and determining ESR1 mutational status in those who develop letrozole resistance. The study includes two interim analyses; at 20% information time, a futility analysis will be conducted, and at 40% information time, both efficacy and futility will be assessed. This is one of the first randomized trials performed in women with primary, advanced LGSOC, and the study is open with 71 patients enrolled at the time of abstract submission.

Fadlalmola, H. A., et al. (2023). "Digital cognitive behavioural therapy (D.CBT) for pregnancy-related depression and sleep disturbances: a systematic review and meta-analysis." Italian Journal of Gynaecology and Obstetrics 35(3): 291-308.
	Objective. Between 5% and 30% of women during the pregnancy and postpartum periods may suffer from depression. The management modalities are ranging from coping and support to medications and electroconvulsive therapy. Our study aimed to assess whether digital cognitive behavioural therapy (D.CBT) can improve pregnancy-related mood and sleep disorders. Materials and Methods. We combed four databases, Web of Science, PubMed, Scopus, and Cochrane Library. Randomized control trials comparing D.CBT with any control group for pregnancy-related depression and sleep disorders were selected for this study. Results. We included 14 studies based on the original data of 12 trials. D.CBT significantly decreased the Patient Health Questionnaire-9 (PHQ-9) after eight weeks compared to the control (MD =-2.77; 95%CI-4.01 to-1.53; p < 0.0001); however, no significant difference after four weeks of intervention or after six weeks of delivery. After eight weeks, D.CBT significantly decreased Inventory of Depression and Anxiety Symptoms (IDAS) (SMD =-0.48; 95%CI-0.78 to-0.18; p = 0.002), while after only four weeks, D.CBT was associated with higher IDAS than the control (SMD = 0.56; 95%CI 0.26 to 0.86; p = 0.0002). Also, D.CBT significantly decreased Generalized Anxiety Disorder Scale (GAD-7) (MD =-1.73; 95%CI-2.63 to-0.83; p = 0.0002), and Insomnia Severity Index (ISI) (MD =-3.45; 95%CI-5.66 to-1.24; p = 0.002) when compared to the control. Conclusions. D.CBT shows some promising outcomes in treating pregnant women's depression and sleep difficulties as decreasing Patient Health Questionnaire-9 (PHQ-9), Depression and Anxiety Symptoms (IDAS), Generalized Anxiety Disorder Scale (GAD-7), and Insomnia Severity Index (ISI), especially after eight weeks of the intervention.Copyright © 2023, EDRA S.p.A. All rights reserved.

Fadoul, R., et al. (2022). "The Modulatory Effect of Adipose-Derived Stem Cells on Endometrial Polyp Fibroblasts." Stem Cells and Development 31(11-12): 311-321.
	Endometrial polyps (EPs) are benign overgrowths of the endometrium, with the potential to cause severe complications, ranging from discomfort to inflammation and infertility. Dysfunction of endometrial fibroblasts may be a critical component leading to the development of polyps. Although surgical intervention is the common remedy for severe cases, it comes with drawbacks, including infection, bleeding, and risk of damage to the cervix and adjacent tissues. Adipose-derived mesenchymal stromal cells (ASCs) are at the focus of modern medicine, as key modulators of tissue homeostasis, inflammation, and tissue repair, rendering them prime candidate agents for tissue regeneration and cell-based therapies. In this study, EPs were isolated from patients admitted to the OB/GYN department at the Galilee Medical Center and extracted fibroblasts (endometrial polyp fibroblasts, EPFs) were isolated and characterized. ASCs were isolated from healthy patients. The effect of EPF- and ASC-conditioned media (CM) on polyp-derived fibroblasts was evaluated, in both 2D and 3D assays, as well as on the expression of matrix-related gene expression. Herein, EPFs exposed to ASC-CM exhibited reduced migration, invasion, contraction of hydrogels, and extracellular matrix deposition, compared with those exposed to EPF-CM. Altogether, this study suggests that ASCs may have a modulating effect on fibroblasts involved in forming EPs and may serve as the basis for conservative treatment strategies aimed at treating severe cases of EPs.© Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.

Fagbemi, F. (2019). "Impact of social support on postnatal depression among adolescent mothers: a systematic literature review." MIDIRS Midwifery Digest 29(1): 20-26.
	BACKGROUND: Postnatal depression (PND) is an important public health issue which affects mother and child. The National Institute of Clinical Excellence (NICE) (2014) suggests that PND is a common problem affecting one in ten women with in a year of giving birth. Studies have discussed the impact of social support on postnatal depression amongst inexperienced mothers such as adolescent women (Kim et al 2014), suggesting that a lack of social support can be a risk factor for postnatal depression in this group of mothers (Brown et al 2012). However, there were no systematic reviews found on this topic. AIM: The aim of this review is to explore the impact of social support on adolescent mothers' postpartum depressive symptoms. Study selection: A database search was carried out across two search engines, EBSCOhost and OVID. The research involved searching for articles that discuss the impact of social support on the psychological health of adolescent mothers. FINDINGS: All the studies identified suggest that social support has an inverse relationship with PND amongst adolescent mothers. CONCLUSION: There is some evidence that receiving social support after birth is important for adolescent mothers, to reduce the risk of postpartum depression.

Fagotti, A., et al. (2021). "Randomized Trial of Primary Debulking Surgery Versus Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer (SCORPION-NCT01461850)." Obstetrical & gynecological survey 76(2): 90‐91.
	
Fahrni, A. C., et al. (2022). "A new titanium-covered transobturator tape for surgical treatment of stress urinary incontinence." International Urogynecology Journal 33(4): 911-918.
	Introduction and hypothesis: To assess the long-term satisfaction, cure rate and safety of a new titanium-covered transobturator tape compared to polypropylene tape for the treatment of stress urinary incontinence (SUI). Method(s): A prospective study was conducted with 151 patients. Seventy patients underwent transobturator sling surgery with titanium tape from 2011 to 2019, and a historical control group (CG) of 81 patients was treated with a noncoated tape and underwent incontinence surgery from 1999 to 2009. We compared patient-reported outcome measures (PROMs) with the incontinence outcome questionnaire (IOQ). Result(s): The median follow-up was 21/2 years in both groups. Based on responses to the IOQ, a statistically significantly shorter time of recovery (IOQ 15: 21.3 +/- 26.4 [TG], 40.2 +/- 38.5 [CG], p = 0.02), improvement of sex life (IOQ 13: 34.1 +/- 29.4 [TG] vs. 65.3 +/- 35.6 [CG], p = 0.01) and less voiding dysfunction (IOQ 19: 30.9 +/- 28.1 [CG], 9.3 +/- 18.6 [TG], p = 0.01) were observed in the TG. Objectively, no postoperative urinary retention was observed in the TG, but four cases were described in the CG. Ten patients needed a reoperation for SUI in the CG compared to three in the TG (p = 0.03). Conclusion(s): The titanium-covered transobturator sling had superior recovery time, improved sexual function and reduced reoperation rate compared to a historical polypropylene group.Copyright © 2021, The Author(s).

Fahy, M. R. (2024). "A review of functional and surgical outcomes of gynaecological reconstruction in the context of pelvic exenteration." Surgical Oncology 52: 101996.
	Background: Radical surgical excision may be the only curative option for patients with advanced pelvic malignancy, but concerns surrounding the functional outcomes and survivorship of patients undergoing exenterative surgery remain. This is especially important in the context of vulvovaginal resection, where patients are often younger and surgery can have a profoundly negative impact on quality of life, body image and overall wellbeing. Reconstructive procedures are an important means of mitigating these adverse effects but outcomes are poorly described. Aim(s): To define the outcomes associated with gynaecological reconstructive procedures following pelvic exenterative surgery and to compare them with the outcomes of those patients who did not undergo reconstruction. Method(s): An international, multicentre retrospective investigation comparing the outcomes of reconstruction with no reconstruction. The protocol was prospectively registered (NCT05074069). Result(s): 334 patients were included. 77 patients had a neovagina reconstructed, 139 patients underwent flap reconstruction and 118 were not reconstructed. Patients who underwent reconstruction had a longer operative time and hospital stay with an increased risk of minor perineal complications. Reconstruction did not confer an increased risk of surgical reintervention, and overall complication rates were equivalent. Procedure-specific major morbidity was 5.2 % and 11.5 % for neovaginal and flap reconstruction, respectively. 66 % of patients undergoing neovaginal reconstruction experienced no long term morbidity. 7 % developed neovaginal stenosis and 12 % suffered disease recurrence. Conclusion(s): Neovaginal reconstruction is safe in carefully selected patients and offers specific advantages over alternative techniques, with few patients requiring reoperation. Primary closure does not increase perineal morbidity.Copyright © 2023 The Authors

Fairclough, E., et al. (2024). "Does variation of surgical technique affect native tissue anterior pelvic organ prolapse repair outcomes?" International Urogynecology Journal 35(1): 51-58.
	Introduction and hypothesis: The Variation in Surgical Technique study (VaST), demonstrated the large variation in surgical techniques used in native tissue (NT) anterior pelvic organ prolapse (POP) repairs. However, there are few comparative studies of different surgical techniques. This study was aimed at exploring whether surgical technique influenced the outcomes of NT anterior POP repairs. Method(s): The surgical techniques of 22 consultant surgeons performing NT anterior POP repairs were filmed and categorised. These surgeons performed 809 anterior repairs within the PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trial (PROSPECT). Logistical regression models were used to determine the influence of the different surgical techniques on subjective and objective outcomes, using data collected during PROSPECT. Result(s): In adjusted multivariate linear regression models, fascial-flap repair was associated with an improved subjective outcome (POP-SS) compared with midline plication (beta = -2.50 [-4.42 to -0.57]; p = 0.01). At 12 months, separate fascial defect repair was associated with a poorer objective outcome than midline plication (OR 6.06 [1.82-3.52], p = 0.006). At 24 months, deep dissection was associated with a poorer POP-SS than superficial dissection (0.32-2.60, p = 0.0). Continuous-locking closure of the skin was also associated with improved POP-SS compared with continuous non-locking closure (12 months: beta = -1.94 [-3.42 to -0.45], p = 0.01). Conclusion(s): Surgical technique may influence the outcome of native tissue anterior POP repairs. Our results should not change practice but inform future research; to develop methods of explicitly recording surgical techniques and allow confirmation of the effect of these aspects of technique on outcome.Copyright © 2023, The Author(s).

Fait, T., et al. (2023). "Treatment of Vulvovaginal Laxity by Electroporation: The Jett Plasma Medical for Her II Study." Journal of Clinical Medicine 12(19): 6234.
	Introduction: Vaginal laxity is a widespread and undertreated medical condition associated especially with vaginal parity. Aim(s): To evaluate the efficacy and safety of electroporation therapy treatment of vulvovaginal laxity by the Jett Plasma for Her II device. Method(s): The Jett Plasma for Her II Study is a multicentric, prospective, randomized, single-blinded, and controlled study. Women presenting with vaginal laxity were randomized to receive electroporation therapy delivered to the vaginal tissue (active-82 patients) vs. therapy with zero intensity (placebo-9 patients). Result(s): A total of 91 subjects whose average age was 48.69 +/- 10.89 were included. Due to the results of a one-way analysis of variance, it may be concluded that in the case of the vaginal laxity questionnaire (VLQ), there is a statistically significant difference between actively treated patients and the placebo group (F1,574 = 46.91; p < 0.001). In the case of the female sexual function index (FSFI), a one-way ANOVA test also showed a statistically significant difference between the actively treated patients and the placebo group (F1,278 = 7.97; p = 0.005). In the case of the incontinence impact questionnaire-7 (IIQ-7), a one-way ANOVA test showed a statistically significant difference between the actively treated patients and the placebo group (F1,384 = 15.51; p < 0.001). It confirms that improvement of vaginal laxity is conjoined with benefits in symptoms of urinary incontinence. Biopsy performed after the end of the treatment shows an increase in the vaginal mucosa thickness by an average of 100.04% in the active group. The treatment was well tolerated with no adverse events. No topical anesthetics were required. Conclusion(s): Treatments of vulvovaginal laxity by electroporation therapy achieved significant and sustainable 12-month effectiveness. Responses to the questionnaires also suggest subjective improvement in self-reported sexual function, incontinence, sexual satisfaction, and urogenital distress.Copyright © 2023 by the authors.

Faith, J., et al. (2022). "Bacterial vaginosis among pregnant women attending antenatal care in LMICs from 2000 to 2020."
	
Fakhri, M., et al. (2023). "Effects of Herbal Products on Menorrhagia: A Systematic Review and Meta-analysis." Journal of Nursing and Midwifery Sciences 10(3).
	Context: Menorrhagia is an important healthcare challenge. Complementary and alternative medicine therapies are strategies with potential positive effects on menorrhagia. Objectives: The aim of this study was to systematically assess the effects of herbal products on menorrhagia. Methods: This was a systematic review and meta-analysis. PubMed, Scopus, Web of Science, Embase, Cochrane Library, Barekat Gostar, Scientific Information Database (SID), Magiran, and IranDoc international and Iranian databases, in addition to the Google Scholar search engine, were searched without any time or language limitation (updated until 02.07.2022). Eligible studies were combined through the random-effects model based on their sample sizes, mean scores, and standard deviations. Data analysis was performed at a significance level of less than 0.05 using STATA software (version 14.0). Results: Nineteen trials on 1715 women (856 and 859 subjects in the control and intervention groups, respectively) were reviewed. After the intervention, menstrual bleeding severity in the first, second, and third cycles (P < 0.001) and the number of menstrual days in the first (P < 0.001), second (P < 0.001), and third (P = 0.487) menstrual cycles significantly decreased in the herbal products group. There were no significant between-group differences regarding the bleeding severity at the pretest (P < 0.001) and in the third cycle (P < 0.001) and the number of menstrual days at the pretest (P = 0.131) and in the second (P < 0.001) and third cycles (P = 0.014). However, the bleeding severity in the intervention group was significantly less than the control group in the first (P < 0.001) and second cycles (P < 0.001), and the number of menstrual days in the intervention group was significantly less than the control group in the first cycle (P = 0.004). Conclusions: Herbal products are effective in significantly reducing bleeding severity and the number of menstrual days among women with menorrhagia, and their effects reduce over time.

Fakhri, S., et al. (2022). "Modulation of TLR/NF-kappaB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy." Frontiers in Oncology 12: 834072.
	Background: Tumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-kappaB (NF-kappaB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-kappaB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance. Objective(s): This is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-kappaB/NLRP signaling pathway in chemotherapy and immunotherapy. Method(s): A comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-kappaB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals. Result(s): Phytochemicals are promising multi-targeting candidates against the TLR/NF-kappaB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-kappaB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted. Conclusion(s): Targeting TLR/NF-kappaB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.Copyright © 2022 Fakhri, Moradi, Yarmohammadi, Narimani, Wallace and Bishayee.

Falahati-Pour Soudeh, K., et al. (2023). "Ovarian Endocrine Status and ART 0utcomes in Women within PCOS Based on Different Testosterone Levels." Indian journal of endocrinology and metabolism 27(5): 440-444.
	Background: It is estimated that in women at reproductive age, the risk of polycystic ovary syndrome (PCOS) is about 5-21%. In PCOS cases with ovulation dysfunction, assisted reproductive techniques (ART) are useful for infertility treatment.; Objective: This study aimed to evaluate the ART outcome in infertile PCOS women based on different testosterone levels. Finally, the relationships between testosterone in different levels and reproductive parameters including endocrine status, the response of ovaries, and pregnancy outcomes were assessed.; Methods: In this retrospective study, 352 infertile PCOS women were examined. The women were categorised into five groups according to their testosterone levels: A = T < 0.4, B = 0.4 < T > 0.6, C = 0.6 < T > 0.8, D = 0.8 < T > 1.0 and E = T > 1.0 ng/dL. All study cases were in similar hyper-stimulation protocol and finally, hormonal profile and ART outcomes were compared between testosterone levels. P value ≤ 0.05 was statistically significant.; Results: In testosterone levels >1.0, the levels of anti-mullerian hormone (AMH) and luteinising hormone (LH) were higher than in other testosterone level groups. AMH ( P = 0.05) and LH ( P = 0.001) levels showed significant differences. No correlation was present between testosterone levels and ART outcomes, including stimulation duration, endometrial thickness, oocyte numbers, numbers of matured oocytes, number of obtained embryos, fertilisation rate, implantation rate clinical pregnancy and abortion rate.; Conclusions: Serum testosterone levels did not show any correlation with pregnancy outcomes in ART cycles of PCOS. However, basal testosterone levels are a good predictor for ovarian reserve and ovarian response. Consequently, we suggest that some prospective studies must be designed to approve the role of testosterone in the prediction of the outcome of pregnancy in ART cycles.; Competing Interests: There are no conflicts of interest. (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Falandry, C., et al. (2021). "Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer: A GINECO/GCIG Randomized Clinical Trial." JAMA Oncology 7(6): 853-861.
	IMPORTANCE: Single-agent carboplatin is often proposed instead of a conventional carboplatin-paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients. OBJECTIVE: To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin-paclitaxel, or conventional every-3-weeks carboplatin-paclitaxel in vulnerable older patients with ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019. INTERVENTIONS: Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m2, on days 1, 8, and 15 every 4 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death. RESULTS: A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee's recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group). CONCLUSIONS AND RELEVANCE: This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin-paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02001272.

Falcão, P., et al. (2021). "Parasacral versus tibial transcutaneous electrical stimulation to treat urinary urgency in adult women: randomized controlled clinical trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 267: 167‐173.
	INTRODUCTION: Urinary urgency is a very strong urge to urinate that is difficult to postpone and control. One of the physiotherapeutic resources that can be used in the treatment of urinary urgency is electrical nerve stimulation. The objective of this study is to investigate the effects of parasacral and tibial nerve transcutaneous electrical stimulation in improving urinary urgency in adult women. MATERIAL AND METHODS: Single‐blinded randomized controlled clinical trial. PARTICIPANTS: Ninety‐nine adult women with urgency. INTERVENTIONS: Transcutaneous electrostimulation for 12, 20‐min sessions, twice a week. The tibial and parasacral groups received a current of F = 10 Hz and 200 μs pulse duration, while the sham group received a current of F = 100 Hz and 100 μs pulse duration, the active electrode placed over the scapula. Primary and secondary outcome measures: The primary outcome measure was urinary urgency, measured by the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ‐OAB) and Overactive Bladder questionnaire‐Validated 8‐Question Awareness Tool (OAB‐V8). Secondary outcomes were quality of life with the King's Health Questionnaire (KHQ) and voiding habits with the 24‐h voiding diary. Assessments occurred pretreatment, after the sixth and 12th post‐treatment sessions and at the 30‐day follow‐up. RESULTS: Both parasacral and tibial groups in the post‐treatment presented fewer episodes of urgency than the sham group. The parasacral group showed better results than the sham group post‐treatment for ICIQ‐OAB scores, and in KHQ domains Impact of Incontinence and task limitations. Parasacral group participants had OAB‐V8 score lower than 8 in the post‐treatment and follow‐up. CONCLUSION: Both tibial and parasacral groups had a positive and similar effect on reducing urinary urgency in adult women. Relative to the quality of life, transcutaneous parasacral electrostimulation was superior to transcutaneous tibial electrostimulation. CLINICAL TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC), http://ensaiosclinicos.gov.br, protocol RBR‐9rf33n.

Falchook, G., et al. (2024). "A Relative Bioavailability, Bioequivalence, and Food Effect Study of Niraparib Tablets in Patients with Advanced Solid Tumors." Clinical therapeutics.
	PURPOSE: The poly (ADP-ribose) polymerase inhibitor niraparib is indicated as maintenance treatment in patients with certain subtypes of advanced ovarian cancer, and is being investigated in patients with other solid tumors. Niraparib is available in 100-mg capsules with a starting dosage of 200 or 300 mg/d. This study assessed the relative bioavailability (BA) and bioequivalence (BE) between a 1 x 300-mg tablet relative to 3 x 100-mg niraparib capsules. In addition, the food effect (FE) of a high-fat meal on the pharmacokinetic (PK) properties of tablet-formulated niraparib was investigated. METHOD(S): This was a US-based, 3-stage, open-label, multicenter, single-crossover, randomized-sequence study. Enrolled patients were 18 years and older, with histologically or cytologically confirmed advanced solid tumors (metastatic or local) and disease progression despite standard therapy. Patients were randomly assigned 1:1 to receive niraparib 1 x 300-mg tablet or 3 x 100-mg capsules in the BA and BE stages or 1 x 300-mg tablet in a fasted or fed (high-fat meal) state in the FE stage. Across all study stages, PK parameters were assessed for 7 days after each dose (tablet or capsule) or prandial state (fasted or fed). In the BA stage, patients crossed over to the other treatment after a 7-day washout period, which was extended to 14 days in the BE and FE stages. Tolerability was assessed for patients who received any amount of niraparib. FINDINGS: The BA-, BE-, and FE-evaluable populations comprised 23, 108, and 19 patients, respectively, who completed both treatment periods in each study stage, had sufficient concentration data to accurately estimate PK parameters without niraparib carryover, and did not experience disqualifying events. PK parameters were similar after dosing with tablet or capsule formulations; the 90% CIs of the geometric least square means for Cmax, AUC0-t, and AUC0- were within the 0.80 to 1.25 BE limits. In the FE stage, Cmax, AUC0-t, and AUC0- were 11%, 32%, and 28% higher, respectively, in the fed versus fasted state. The safety population included 29, 168, and 28 patients in the BA, BE, and FE stages, respectively, who received niraparib. No new safety signals were identified. IMPLICATIONS: Niraparib tablets were found to be bioequivalent to capsules. A modest (<=32%) FE was observed with a high-fat meal, but was not considered to be clinically meaningful, given niraparib's PK variability. CLINICALTRIALS: gov identifier: NCT03329001. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.Copyright © 2024 GSK. Published by Elsevier Inc. All rights reserved.

Falchook Gerald, S., et al. (2023). "A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors." Investigational New Drugs 41(3): 493-502.
	Adavosertib selectively inhibits Wee1, which regulates intra-S and G2/M cell-cycle checkpoints. This study investigated dosing schedules for adavosertib monotherapy, determining the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) in patients with advanced solid tumors.Patients received oral adavosertib qd or bid on a 5/9 schedule (5 days on treatment, 9 days off) in 14-day cycles, or qd on one of two 5/2 schedules (weekly, or for 2 of 3 weeks) in 21-day cycles. Safety, efficacy, and pharmacokinetic analyses were performed.Sixty-two patients (female, 64.5%; median age, 61.5 years; most common primary tumors: lung [24.2%], ovary [21.0%]) received treatment (qd schedules, n = 50; bid schedules, n = 12) for 1.8 months (median). Median time to maximum adavosertib concentration was 2.2-4.1 h; mean half-life was 5-12 h. Adverse events (AEs) caused dose reductions, interruptions and discontinuations in 17 (27.4%), 25 (40.3%) and 4 (6.5%) patients, respectively. Most common grade ≥ 3 AEs were anemia, neutropenia (each n = 9, 14.5%) and diarrhea (n = 8, 12.9%). Seven (11.3%) patients experienced 10 treatment-related serious AEs (pneumonia n = 2 [3.2%], dehydration n = 2 [3.2%], anemia n = 1 [1.6%], febrile neutropenia n = 1 [1.6%], and thrombocytopenia n = 1 [1.6%]). Overall objective response rate was 3.4% (2/58); disease control rate was 48.4% (30/62); median progression-free survival was 2.7 months.MTDs were 125 mg (bid 5/9) and 300 mg (qd 5/9 and 5/2 for 2 of 3 weeks); RP2D was 300 mg (qd 5/2 for 2 of 3 weeks). The safety profile was manageable, acceptable, and generally concordant with the known safety profile. (© 2023. The Author(s).)

Falchook, G. S., et al. (2021). "A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors." Investigational New Drugs 39(5): 1284-1297.
	Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).

Falcinelli, M., et al. (2023). "Propranolol reduces IFN-γ driven PD-L1 immunosuppression and improves anti-tumour immunity in ovarian cancer." Brain, behavior, and immunity 110: 1-12.
	The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and in vivo EOC models. Noradrenaline (NA), an adrenergic agonist, did not directly regulate PD-L1 expression but PD-L1 was significantly upregulated by IFN-γ in EOC cell lines. IFN-γ also increased PD-L1 on extracellular vesicles (EVs) released by ID8 cells. PRO significantly decreased IFN-γ levels in primary immune cells activated ex vivo and showed increased viability of the CD8 + cell population in an EV-immune cell co-incubation. In addition, PRO reverted PD-L1 upregulation and significantly decreased IL-10 levels in an immune-cancer cell co-culture. Chronic behavioural stress increased metastasis in mice while PRO monotherapy and the combo of PRO and PD-(L)1 inhibitor significantly decreased stress-induced metastasis. The combined therapy also reduced tumour weight compared to the cancer control group and induced anti-tumour T-cell responses with significant CD8 expression in tumour tissues. In conclusion, PRO showed a modulation of the cancer immune response by decreasing IFN-γ production and, in turn, IFN-γ-mediated PD-L1 overexpression. The combined therapy of PRO and PD-(L)1 inhibitor decreased metastasis and improved anti-tumour immunity offering a promising new therapy.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Falerina, P., et al. (2023). "Cost-effectiveness of postpartum depression screening: A Systematic Review of Economic Evaluation."
	
Fallah, P., et al. (2023). "Improving health equity among ovarian cancer patients enrolled in an Enhanced Recovery After Surgery (ERAS) pathway (2212)." Gynecologic Oncology 176(Supplement 1): S264-S265.
	Objectives: It is unknown whether Enhanced Recovery After Surgery (ERAS) protocols may improve health equity among ovarian cancer patients through standardizing preoperative counseling and establishing standards of care. Method(s): A cohort study was performed among stage III and IV ovarian cancer patients undergoing surgery at one academic institution from January 2010 to December 2021. The ERAS program was implemented in March 2017. The pre-ERAS period was defined as January 2010 to July 2015, and the post-ERAS period was defined as March 2017 to December 2021, excluding the transitional period between 2015 and 2017 when ERAS was starting to be implemented. A chart review was performed on surgical complications (within 30 days of surgery), including reoperations, readmissions, ICU admissions, blood transfusions during the primary stay, pneumonia, wound infections, etc. (Table 1). chi2 and Fisher's exact analyses were performed to compare outcomes by race during the pre-ERAS and post-ERAS periods. Result(s): Among 794 ovarian cancer patients (42.9% pre-ERAS, 57.1% post-ERAS), 86 patients (10.8%) were non-White overall, and the percentage of non-White patients increased over time (7.9% pre-ERAS, 13.0% post-ERAS). Before ERAS was implemented, 22.2% of non-White women versus 9.6% of White women were readmitted within 30 days of surgery (P = 0.040, Table 1). Non-White women also experienced a higher rate of receiving blood transfusions compared to non-White women (48.1% vs 29.6%, P = 0.046), with no other significant differences in complications noted during the pre-ERAS period. In the post-ERAS period, readmissions were reduced by half among non-White women, which were no longer noted to be significantly different by race (11.9% vs 9.9%, P = 0.641). Similarly, there was no significant difference in blood transfusions by race in the post-ERAS period. However, the rate of ICU admissions was significantly higher among non-White women post-ERAS (8.5% vs 2.0%, P = 0.018), which was similar to pre-ERAS data, although not statistically significant during that period (7.4% vs 3.2%, P = 0.244). There were no other significant differences in complications in the post-ERAS period. Conclusion(s): ERAS programs may improve health equity by reducing the need for blood transfusions and reducing readmissions by half among non-white women with ovarian cancer. The reduction in readmissions merits further investigation with a larger cohort, as this has potentially far-reaching implications in reducing healthcare expenditures. Future studies should also focus on specific aspects of ERAS programs that may reduce the chances of readmission among minority women with ovarian cancer. [Formula presented]Copyright © 2023

Fallon, V., et al. (2021). "Psychosocial experiences of postnatal women during the COVID-19 pandemic. A UK-wide study of prevalence rates and risk factors for clinically relevant depression and anxiety." Journal of Psychiatric Research 136: 157-166.
	BACKGROUND: When the vulnerabilities of the postnatal period are combined with the impact of the COVID-19 pandemic, psychosocial outcomes are likely to be affected. Specifically, we aim to: a) explore the psychosocial experiences of women in the early postnatal period; b) describe prevalence rates of clinically relevant maternal anxiety and depression; and c) explore whether psychosocial change occurring as a result of COVID-19 is predictive of clinically relevant maternal anxiety and depression. METHODS: A sample of UK mothers (N = 614) with infants aged between birth and twelve weeks were recruited via convenience sampling. A cross-sectional survey design was utilised which comprised demographics, COVID-19 specific questions, and a battery of validated psychosocial measures, including the EPDS and STAI-S which were used to collect prevalence rates of clinically relevant depression and anxiety respectively. Data collection coincided with the UK government's initial mandated "lockdown" restrictions and the introduction of social distancing measures in 2020. FINDINGS: Descriptive findings from the overall sample indicate that a high percentage of mothers self-reported psychological and social changes as a result of the introduction of social distancing measures. For women who reported the presence of psychosocial change, these changes were perceived negatively. Whilst seventy women (11.4%) reported a current clinical diagnosis of depression, two hundred and sixty-four women (43%) reported a score of ≥13 on the EPDS, indicating clinically relevant depression. Whilst one hundred and thirteen women (18.4%) reported a current clinical diagnosis of anxiety, three hundred and seventy-three women (61%) reported a score of ≥40 on STAI-S, indicating clinically relevant anxiety. After accounting for current clinical diagnoses of depression or anxiety, and demographic factors known to influence mental health, only perceived psychological change occurring as a result of the introduction of social distancing measures predicted unique variance in the risk of clinically relevant maternal depression (30%) and anxiety (33%). INTERPRETATION: To our knowledge, this is the first national study to examine the psychosocial experiences of postnatal women during the COVID-19 pandemic in the UK. Prevalence rates of clinically relevant maternal depression and anxiety were extremely high when compared to both self-reported current diagnoses of depression and anxiety, and pre-pandemic prevalence studies. Perceived psychological changes occurring as a result of the introduction of social distancing measures predicted unique variance in the risk for clinically relevant maternal depression and anxiety. This study provides vital information for clinicians, funders, policy makers, and researchers to inform the immediate next steps in perinatal care, policy, and research during COVID-19 and future health crises.

Fameli, A. L., et al. (2022). "Assessment of childbirth-related post traumatic stress disorder in Australian mothers: Psychometric properties of the City Birth Trauma Scale." Journal of Affective Disorders.
	BACKGROUND: The City Birth Trauma Scale (BiTS; Ayers, Wright & Thornton, 2018) is self-report measure of Post-Traumatic Stress Disorder (PTSD) symptoms following childbirth, based on DSM-5 criteria. We report on the first study of the psychometric properties of the BiTS in the Australian population. METHOD(S): Participants were mothers of infants aged 0-12months (N=705), who completed the BiTS and measures of related constructs. Confirmatory factor analysis was performed to assess the factor structure of the BiTS. Examination of the reliability, convergent, divergent and discriminant validity and acceptability of the BiTS was also examined. RESULT(S): Confirmatory factor analysis supported a bi-factor model of Birth-related Symptoms (BRS) and General Symptoms (GS) of post-partum PTSD as well as a global CB-PTSD factor. Internal consistency was found for the BiTS total scale and two proposed subscales (BRS and GS). BiTS total scores were significantly associated with an established measure of PTSD, providing support for convergent validity. Evidence of discriminant validity was examined by comparing the BiTS to an established measure of postpartum depression. LIMITATIONS: The present sample may over-represent participants with traumatic birth experiences in comparison to the general public. Furthermore, use of self-report measures limits the capacity to confirm the diagnostic status of participants. CONCLUSION(S): These findings suggest that the BiTS is a valid and reliable measure of childbirth-related PTSD, suited for use in postpartum populations. Total scores on the measure may be informative for clinical and research purposes, while evidence suggests strong support for interpretation of subscale scores.Copyright © 2022. Published by Elsevier B.V.

Fan, C., et al. (2022). "Vascular endothelial growth factor (VEGF) targeting therapy for persistent, recurrent, or metastatic endometrial cancer."
	
Fan Chi, W., et al. (2022). "Systematic Review of Black Cohosh ( Cimicifuga racemosa ) for Management of Polycystic Ovary Syndrome-Related Infertility." Journal of pharmacy practice 35(6): 991-999.
	Polycystic ovary syndrome (PCOS) is a common cause of female infertility. To conduct a systematic review assessing the efficacy and safety of black cohosh for ovulation-induction through hormone regulation and increased endometrial thickness to improve pregnancy rates in women with PCOS-related infertility. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used. A search of Medline, Embase, International Pharmaceutical Abstracts, Science Direct, and Cumulative Index of Nursing and Allied Health Literature spanning origin to December 19, 2020 was conducted using keywords and permutations of "black cohosh" and "PCOS." A search for "PCOS" in the National Clinical Trials database and International Clinical Trials Registry Platform was conducted in December 2020 to identify additional records. Eligibility criteria included reported efficacy or safety outcomes; studies in women with PCOS; English language; and primary literature. Eligible records were evaluated using applicable risk-of-bias tools. A total of 181 records were screened after deduplication from 207 results. Two randomized controlled trials (RCT) met inclusion criteria. Review of 1386 records from clinical trial registries and subsequent scoping searches resulted in identification of 4 additional records (3 published). Improvement in hormone regulation and endometrial thickness were found for black cohosh groups compared to clomiphene citrate (CC). Three RCTs reported improved pregnancy rates using black cohosh plus CC. There were no differences in adverse events. Studies demonstrated several risk-of-bias concerns. There is a lack of high-quality evidence supporting the effectiveness of black cohosh for improving pregnancy rates in PCOS-related infertility. Short-term use of black cohosh appears to be safe.

Fan, H., et al. (2021). "Differences in the individual curative effect of acupuncture for obese women with polycystic ovary syndrome based on metagenomic analysis: study protocol for a randomized controlled trial." Trials 22(1): 454.
	Background: Polycystic ovary syndrome is a common cause of infertility and shows a high incidence in women of reproductive age. Acupuncture is an appropriate adjunctive treatment for PCOS. However, the add-on effect of acupuncture as an adjunctive treatment for obese women with PCOS has not been studied, and previous studies indicate that there are individual differences in the curative effect of acupuncture, while deeper research on the mechanism of differences in the individual curative effect of acupuncture for obese women with PCOS is still lacking. This trial aims to assess the add-on treatment efficacy of acupuncture for obese women with PCOS and to explore the role of the gut microbiome on the differences in the individual curative effect of acupuncture based on metagenomic analysis.; Methods/design: This is an open-label, randomized, controlled trial. A total of 86 obese women with PCOS will be recruited. Subjects will be randomly assigned to a study group and a control group in a 1:1 ratio, with 43 subjects in each group (10 patients from each group who meet the study criteria will participate in the metagenomic analysis). An additional 10 subjects who meet the study criteria will be recruited to a healthy control group. The study group will receive acupuncture and clomiphene citrate treatment; the control group will only receive clomiphene citrate. Acupuncture treatment will be conducted three times a week from the fifth day of menstruation or withdrawal bleeding until the start of the next menstruation, for up to three menstrual cycles. The primary outcome will be LH/FSH. The secondary outcomes will comprise biometric features, hormone biomarkers, metabolic biomarkers, inflammatory biomarkers, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and metagenomic analysis. The outcomes will be measured at baseline and post-intervention. Data will be analyzed using SPSS 19.0, and the gut microbiome will be analyzed using metagenomic analysis.; Discussion: In this study, we are evaluating the add-on effects of acupuncture and exploring the mechanism of the differences in the individual curative effect of acupuncture based on the gut microbiome, which may provide evidence to explain the different outcomes of different trials on acupuncture for PCOS and hopefully to provide a new aspect to study the mechanism of acupuncture's treatment effect.; Trial Registration: Chinese Clinical Trial Registry ChiCTR2000029882 . Registered on 16 February 2020. (© 2021. The Author(s).)

Fan, J., et al. (2021). "Anesthesia effect of ketorolac tromethamine combined with dezocine for painless induced abortion and its effect on stress response and postoperative uterine contraction pain." 中国计划生育学杂志 29(5): 889‐894.
	Objective: To investigate the anesthesia effect of ketorolac tromethamine combined with dezocine in painless induced abortion and its effect on women's stress response and postoperative uterine contraction pain. Methods: A total of 240 women who chose to undergo voluntary painless induced abortion in our hospital from October 2019 to March 2020 were selected and divided into dezocine group (group A) and ketorolac group (group B) by random number table. , Dezocine combined with ketorolac group (group C) and control group with 60 cases each. Group A was given intravenous injection of 0.1 mg/kg dezocine 15 minutes before operation, group B was given intravenous injection of 30 mg ketorolac tromethamine 30 minutes before operation, and group C was given a combination of 0.1 mg/kg dezocine and 30 mg ketorolac tromethamine. alcohol, and the control group was injected with 1 μg/kg fentanyl. The anesthesia effect and related clinical indexes including operation time, propofol dosage, orientation recovery time, postoperative recovery time, and blood oxygen saturation (SpO2) value after anesthesia were compared in each group. Hemodynamic indexes at different time points during operation included Mean arterial pressure (MAP), heart rate (HR) and stress hormone levels, uterine pain scores and adverse reactions at different time points after waking up. Results: The excellent and good rate of anesthesia effect in group C (91.7%) was higher than that in the other three groups (P<0.05). The dosage of propofol (134.3±16.4 mg) in group C was less than that in the other three groups, and the recovery time (4.4±1.2min) and orientation recovery time (4.3±1.1min) were shorter than those in the other three groups. SpO2 (98.6±1.1min) after anesthesia 2.3%) higher than the other 3 groups (P<0.05). HR, MAP and levels of stress hormones at 5 min after surgery (T1) and 5 min after surgery (T2) in each group were higher than those before surgery (T0), and group C < group A < group B < control group, and 1 min after waking up, The 10‐min pain visual analogue scale score in group C (3.2±0.7 points, 2.5±0.6 points) was lower than that in the other three groups, and the incidence of adverse reactions in group C (11.7%) was lower than that in the other three groups (all P<0.05). Conclusion: The prophylactic application of dezocine and ketorolac tromethamine before analgesic abortion to assist anesthesia is effective, can effectively reduce the dosage of propofol, reduce the body's hemodynamic fluctuation and stress response, and improve the operation efficiency. Post‐analgesia effect and resuscitation quality, and safety is also higher.

Fan, L., et al. (2022). "Biomarker testing to guide first-line PARP inhibitor maintenance for patients with advanced ovarian cancer after response to first- line platinum chemotherapy: A cost-effectiveness study (382)." Gynecologic Oncology 166(Supplement 1): S195.
	Objectives: Multiple poly-ADP ribose polymerase inhibitor (PARPi) maintenance treatment (mTx) options are available for patients with advanced ovarian cancer after response to first-line platinum chemotherapy (PSaOC). Olaparib (O) is an option as monotherapy for patients with BRCA1/2 mutations or in combination with bevacizumab (O+B) for Homologous Recombination Deficiency (HRD+) patients. Meanwhile, niraparib (N) is approved irrespective of biomarker status. This study aimed to evaluate the cost-effectiveness of biomarker testing and treatment with PARP inhibitor mTx in PSaOC patients from the perspective of a US payer. Method(s): Ten testing and treatment strategies (Table 1) were evaluated, representing common biomarker testing (none, BRCA or HRD) and mTx (O, O+B, N, B) in approved populations. PAOLA-1 trial data were used to build a lifetime horizon partitioned survival model with four health states, including progression-free (PFS), post 1st progression (PP1), post 2nd progression (PP2), and death. PFS was modeled through parametric mixture survival modeling to a landmark survival point at five years. Patients who remain PFS at year five are assumed to be long-term survivors. Time to PP2 and OS was modeled by fitting standard parametric models, and time on treatment data was informed by respective trials (up to 24m for O, 15m for B, treat to progression for N). The hazard ratio (HR) of PFS for O+B versus N (0.57 for HRD+/ITT; 0.46 for BRCA+) and O+B versus O (0.71 for BRCA+) were obtained from matching adjusted indirect comparison (MAIC) between PAOLA1 and PRIMA, and PAOLA1 and SOLO1. The HRs for OS are informed by PFS benefits and published OS data. The incremental cost-effectiveness ratios (ICERs) were calculated. Result(s): Strategy 2 (S2, no testing, B) had the lowest cost while S10 (HRD testing, O+B for HRD+ and B for HRD-) had the greatest life- years (LYs) and quality-adjusted life-years (QALYs). All of the niraparib strategies were dominated (i.e., had higher cost, lower LY/ QALYs), compared to at least one other strategy (Table 1). When compared to S2, S8 had lower ICERs than S4 ($41,204 per LY and $48,211 per QALY for S8 vs S2). S10 had an ICER of $66,588 per LY and $82,321 per QALY compared to S8. Conclusion(s): HRD testing followed by O+B for BRCA-/HRD+, O for BRCA+ and B for HRD- (S8) is highly cost-effective, dominating six strategies (all except 2, 4 &10) and having ICERs < $50,000/QALY compared to the least costly strategy (S2). Replacing O with O+B in BRCA+ patients (S10) improves outcomes, with ICER < 100,000/QALY compared to S8. All strategies involving niraparib were dominated by other approaches. An HRD biomarker-guided approach followed with O+/-B treatment in HRD+ patients provides the greatest LY and QALYs with good economic value.Copyright © 2022 Elsevier Inc.

Fan, L., et al. (2021). "Olaparib in combination with bevacizumab compared to bevacizumab monotherapy for the first-line maintenance treatment of advanced ovarian cancer: a cost-effectiveness analysis." Gynecologic Oncology 162(Supplement 1): S216-S217.
	Objectives: The addition of maintenance olaparib to bevacizumab (OLAP+BEV) demonstrated significant progression-free survival (PFS) benefit vs BEV alone in the randomized trial PAOLA-1 in advanced ovarian cancer patients with homologous recombination deficiency (HRD)-positive tumors. We aim to quantify the health and economic impact by evaluating the US cost-effectiveness of OLAP+BEV relative to BEV as a maintenance treatment for women with advanced ovarian cancer who had partial or complete response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status Methods: Our economic model was a cohort-level four state partitioned survival model with a lifetime horizon. States were progression-free, post first progression, post second progression, and death, modelled using first PFS (PFS1), second PFS (PFS2) and overall survival (OS) outcomes from the PAOLA-1 trial. This approach captured multiple progressions, and the differing health state utility after each progression. PFS1 was modelled through parametric mixture survival modeling to a landmark survival point at 5 years, beyond which, patients who have not progressed are assumed to experience all-cause mortality as the general population. PFS2 and OS were modelled by fitting standard parametric models, and time on treatment data was used directly from PAOLA-1, with a treatment cap of 24 months for OLAP and 15 months for BEV. The cost of HRD testing was calculated as unit cost divided by prevalence and was included as a one-time cost for OLAP+BEV arm. US-based health state utility values were analyzed by applying the methods developed by Pickard. The analyses were conducted from a US healthcare payer perspective, with an annual discount rate of 3%. We also explored the robustness of results using deterministic (DSA) and probabilistic sensitivity analysis. Result(s): At year 5, 45.1% and 16.9% patients remained PFS from OLAP+BEV and BEV arm, respectively. The results showed that compared with bevacizumab alone, OLAP+BEV led to a gain in quality-adjusted life years (2.89 QALYs gain) and life years (3.43 Lys gain) but resulted in higher costs, leading to a deterministic incremental cost-effectiveness ratio (ICER) of $75,276 per QALY. OLAP+BEV had an 87.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. DSA identified efficacy (PFS and OS parameters), subsequent treatment and utility values as key model drivers. [Formula presented] Conclusion(s): OLAP+BEV is associated with LY and QALY gain, and is cost effective for US payers relative to BEV monotherapy for the treatment of women with advanced, HRD-positive ovarian cancerCopyright © 2021 Elsevier Inc.

Fan, L., et al. (2021). "Effectiveness of non-pharmacological interventions for postpartum depression:an umbrella review protocol."
	
Fan, L., et al. (2020). "Traditional uses, botany, phytochemistry, pharmacology, separation and analysis technologies of Euonymus alatus (Thunb.) Siebold: A comprehensive review." Journal of Ethnopharmacology 259: 112942.
	Ethnopharmacological relevance: Euonymus alatus (Thunb.) Siebold (E. alatus), a well-known medicinal plant, has been widely used thousands of years in China for the treatment of various diseases such as urticaria, dysmenorrhea, wound, dysentery, blood stasis, rheumatism and arthritis. Due to the extensive application of E. alatus in the fields of ethnopharmacological usage, the pharmaceutical researches of E. alatus keeps deepening. Aim of the study: This paper reviewed and summarized the integrated research progress of this medicinal plant. A comprehensive summary and comparison of traditional usages, botany, phytochemistry, pharmacology, toxicology, separation and analysis technologies of the E. alatus highlight recent scientific advances, which provides new insights into the research and development of this medicinal plant and would be helpful to promote the research situation of underlying pharmacological mechanisms and further utilizations of E. alatus. Material(s) and Method(s): Literature survey was carried out via classic books of herbal medicine, PhD. and MSc. Dissertations. Online scientific databases including Pubmed, SciFinder, Science Direct, Scopus, the Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI) and others were searched up to February 2020 to identify eligible studies. All literatures of the research subject are analyzed and summarized in this review. Result(s): The E. alatus has been widely used in traditional practice in China, Korea and other Asian Countries. In the study of phytochemistry, more than 230 chemical constituents have been isolated and identified from E. alatus, including sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, phenylpropanoids, lignans, steroids, alkaloids and other compounds. Among them, literature reports show that flavonoids and steroids are the most important bioactive substances found in this plant. A number of researches also have shown that extracts and compounds from E. alatus exert a wide spectrum of pharmacological effects, including antidiabetic effect, anti-tumor effects, anti-inflammatory effects, hepatoprotective effects, antioxidant effects, antibacterial effects, as well as other effects. However, most of the studies without clinical research. Research into plant's toxicological effects has also been limited. In addition, this review also summarizes and compares the separation and analysis technologies of E. alatus. Conclusion(s): E. alatus has potential for the treatment of many diseases, especially tumors and diabetes. But many traditional uses of E. alatus have not been validated by current investigations. Additionally, modern studies haven't gone far enough into its pharmacological effects and the corresponding chemical constituents, more efforts should be made to illuminate the underlying mechanisms of E. alatus for treatment of tumors and diabetes. Moreover, the toxicological effects of this plant can be further studied. Currently, there are limited studies on its side effects and toxicological effects, which should provide further guidance for the safety of clinical use.Copyright © 2020 Elsevier B.V.

Fan, L., et al. (2022). "Cost comparison of adverse event management among breast and ovarian cancer patients treated with poly (ADP-ribose) polymerase inhibitors: analysis based on phase 3 clinical trials." Journal of market access & health policy 10(1): 2078474.
	Background: The economic impact of adverse events (AEs) for poly (ADP-ribose) polymerase inhibitors (PARPis) in ovarian or breast cancer has not been widely evaluated.; Objective: Compare PARPi-related AE management costs from a US payer perspective.; Methods: The frequency of treatment-related grade 3-4 AEs was obtained from published clinical trials of PARPis for the treatment of advanced ovarian cancer (AOC), platinum-sensitive recurrent ovarian cancer (PSROC), and metastatic breast cancer (MBC). AE management costs per patient (2020 USD) per treatment course were calculated by multiplying the AE unit costs by the frequency of AEs for each arm of each trial. Sensitivity analyses were conducted according to the lower and upper limits of the 95% confidence interval for AE rates and unit costs, respectively. Scenarios were also performed to explore the uncertainty of outcomes.; Results: Total AE management costs in AOC were: $3,904, olaparib; $5,595, olaparib plus bevacizumab; and $12,215, niraparib. In PSROC, total costs were: $3,894, olaparib; $6,001, rucaparib; and $11,492, niraparib, and in MBC: $3,574, olaparib; and $9,489, talazoparib. Hematological toxicities were the key drivers of AE management costs for PARPis.; Conclusions: The main AEs among PARPis were hematological. Olaparib was associated with lower AE costs compared to other PARPis.; Competing Interests: LF, DM, MM and JRE are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. YZ and PM are employed by Wickenstones Ltd, a company that received consultancy fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. AM and PG are employees of AstraZeneca PLC. (© 2022 PM and I are employed by Wickenstones Ltd, who was contracted by Merck Sharp & Dohme LLC to perform the research reported in this paper. Authors LF, DM, MM and JRE are employees of Merck Sharp & Dohme LLC while AM and PG are employees of AstraZeneca PLC ,. Published by Informa UK Limited, trading as Taylor & Francis Group.)

Fan, L. X., et al. (2022). "Cx32 promotes autophagy and produces resistance to SN-induced apoptosis via activation of AMPK signalling in cervical cancer." International journal of oncology 60(1): 5300.
	The roles of gap junctions (GJs) and its components, connexins, in the autophagy of cervical cancer cells have been rarely investigated. Our previous study demonstrated that connexin 32 (Cx32) exerted an anti-apoptotic effect on cervical cancer. However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells is not well defined. The present study aimed to investigate the role of Cx32 on autophagy and apoptosis inhibition in cervical cancer cells. The expression levels of Cx32 and the autophagy-associated protein LC3-II in paracancerous cervical tissues (n=30) and cervical cancer (n=50) tissues were determined via western blotting. In total, 45 cervical cancer specimens were used to evaluate the clinical relevance of Cx32 and LC3-II. It was found that both Cx32 and LC3-II were upregulated in cervical cancer tissues compared with those in paracancerous cervical tissues. The effect of Cx32 on autophagy was examined by detecting the change of LC3-II using western blotting, transfection with enhanced green fluorescent protein-LC3 plasmid and transmission electron microscopy analysis. Overexpression of Cx32 significantly enhanced autophagy in HeLa-Cx32 cells, whereas knockdown of Cx32 suppressed autophagy in C-33A cells. The flow cytometry results demonstrated that Cx32 inhibited the apoptosis of cervical cancer cells by promoting autophagy. Moreover, Cx32 triggered autophagy via the activation of the AMP-activated protein kinase (AMPK) signalling, regardless of the presence or absence of GJs. Collectively, it was identified that Cx32 exerted its anti-apoptotic effect by activating autophagy via the AMPK pathway in cervical cancer, which demonstrates a novel mechanism for Cx32 in human cervical cancer progression.Copyright © 2022 Spandidos Publications. All rights reserved.

Fan, P., et al. (2023). "Parent-Performed Infant Massage for Improving Parental Mental State Within 18 Months Postpartum: A Systematic Review." Journal of psychosocial nursing and mental health services 61(4): 52-59.
	The aim of the current review was to assess whether parent-performed infant massage (PPIM) could effectively improve the mental state of parents during the postpartum period. Several international electronic databases were thoroughly searched for relevant articles. Included studies observed the influence of PPIM on the mental state of parents of healthy full-term infants within 18 months postpartum or medically stable preterm infants during hospitalization after birth. Nine studies were included, which observed one or more aspects of parental mental state, including depression, anxiety, parental stress, or general mood state. Characteristics of participants, massage protocols, and outcome measures were heterogenous; hence, results regarding the influence of PPIM on parental mental state were inconsistent. Upon further investigation, 10-minute, home-based PPIM for at least 4 weeks is advisable for maternal depression within 5 months postpartum. Moreover, PPIM in a neonatal intensive care unit is advisable for improving the general mood of mothers of preterm infants. Additional methodologically rigorous studies are needed to provide stronger evidence. [Journal of Psychosocial Nursing and Mental Health Services, 61(4), 52-59.].

Fan, Y., et al. (2022). "Metformin anticancer: Reverses tumor hypoxia induced by bevacizumab and reduces the expression of cancer stem cell markers CD44/CD117 in human ovarian cancer SKOV3 cells." Frontiers in Pharmacology 13: 955984.
	Background: The occurrence and development of solid tumors depend on the blood supply in the tumor microenvironment (TME). Blocking angiogenesis is a new therapeutic strategy to inhibit tumor growth. The anti-angiogenic drug bevacizumab has been approved for gynecological malignancies, especially for advanced recurring cervical cancers and recurring ovarian cancers (OC). Studies in OC have shown a limited effect of bevacizumab in the general population, with a slight improvement in progression-free survival (PFS) and no effect on overall survival (OS). This might be related to the bevacizumab's role in aggravating the hypoxia in the TME, which helps maintain the stemness of ovarian cancer stem cells (CSCs) and promotes the invasion and metastasis of cancer cells. Drugs that target CSCs, such as metformin, may enhance the efficacy of anti-vascular therapies. Therefore, this study aimed to evaluate the effect of metformin combined with bevacizumab on the proliferation of OC cells both in vitro and in vivo , as well as on tumor hypoxia and tumor stem cell markers of human ovarian cancer SKOV3 cells. Methods: The OC cell model SKOV3 was treated with metformin, bevacizumab, and cisplatin alone or in combinations. Cell Counting Kit-8 (CCK-8) was used to measure the rate of cell proliferation. Metformin and bevacizumab were studied in vivo in nude mice. SKOV3 cells were transplanted subcutaneously in nude mice, and different drug interventions were performed after tumor formation, including blank control, bevacizumab alone, metformin alone, cisplatin alone, bevacizumab + metformin, bevacizumab + cisplatin, metformin + cisplatin, and bevacizumab + metformin + cisplatin treatments. The growth of transplanted tumors was routinely monitored and visualized by the tumor growth curve. We used flow cytometry to examine the proportion of CD44 + /CD117 + CSCs in each group. The immunohistochemistry (IHC) method was applied to detect expressions of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α), and microvascular density-associated factor CD34 in tumor cells. The limit dilution method was used to re-inject tumor cells in nude mice to examine the tumor recurrence rate. Results: Combination therapy of metformin and bevacizumab significantly reduced the proliferation rate of SKOV3 cells and the growth rate of transplanted tumors in nude mice compared with the monotherapy effects. In vivo results showed that metformin significantly reduced the proportion of CD44 + /CD117 + CSCs ( p < 0.01). Although bevacizumab increased the proportion of CD44 + /CD117 + CSCs, the addition of metformin did offset this fluctuating trend. The combination of bevacizumab, metformin, and cisplatin efficiently decreased the proportion of CSCs in the OC animal model. IHC results exhibited that expressions of VEGF, CD34, and HIF-1α in transplanted tumors were decreased by metformin alone compared with the control ( p < 0.05). In the bevacizumab treatment, VEGF, and CD34 expressions were decreased, while that of HIF-1α was increased, suggesting that the degree of hypoxia was differentially aggravated after the bevacizumab treatment. The VEGF, CD34, and HIF-1α expressions in the bevacizumab + metformin + cisplatin group were the lowest among all other treatment groups ( p < 0.05). Subcutaneous statistics of nude mice reseeded by the limit dilution method showed that the tumor recurrence rate in the bevacizumab + metformin + cisplatin group was relatively lower. Conclusion: Metformin, bevacizumab combined with platinum-based chemotherapy can significantly inhibit the growth of ovarian cancer cells and transplanted tumors, which is due to the reduction of the proportion of CD44 + /CD117 + CSCs and the alleviation of hypoxia in the tumor microenvironment. Therefore, this may be a reasonable and promising treatment regimen.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 22 Fan, Cheng, Liu, Liu, Lowe, Li, Bentley, King, Tuason, Zhou, Sun and Zhang.)

Fan, Z., et al. (2023). "Ovarian cancer treatment and natural killer cell-based immunotherapy." Frontiers in Immunology 14: 1308143.
	Background: Ovarian cancer (OC) is one of the malignant tumors that poses a serious threat to women's health. Natural killer (NK) cells are an integral part of the immune system and have the ability to kill tumor cells directly or participate indirectly in the anti-tumor immune response. In recent years, NK cell-based immunotherapy for OC has shown remarkable potential. However, its mechanisms and effects remain unclear when compared to standard treatment.; Methods: To explore the value of NK cell-based immunotherapy in the treatment of OC, we conducted a literature review. In comparison to standard treatment, our focus was primarily on the current anti-tumor mechanisms, the clinical effect of NK cells against OC, factors affecting the structure and function of NK cells, and strategies to enhance the effectiveness of NK cells.; Results: We found that NK cells exert their therapeutic effects in OC through mechanisms such as antibody-dependent cell cytotoxicity, perforin release, and granule enzyme secretion. They also secrete IFN-γ and TNF-α or engage in Fas/FasL and TRAIL/TRAILR pathways, mediating the death of OC cells. In clinical trials, the majority of patients experienced disease stability with mild side effects after receiving NK cell-based immunotherapy, but there is still a lack of high-quality research evidence regarding its clinical effectiveness. OC and prior experience with standard treatments have an effect on NK cells, and it may be considered to maximize NK cell effects through the modulation of the tumor microenvironment or combination with other therapies.; Conclusions: In this review, we have summarized the current evidence of NK cell applications in the treatment of OC. Furthermore, factors and strategies that influence and enhance the role of NK cell immunotherapy are discussed.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Fan, Han, Fan and Zhao.)

Fanfani, F. (2023). "Robotic-assisted Versus Conventional Laparoscopic Surgery in Obese Patients With Early Endometrial Cancer." ClinicalTrials.gov.
	No Results Available Procedure: Robot-assisted surgery|Procedure: Laparoscopic surgery Conversion rate|Difference in overall duration of surgery|Difference in perioperative complications|Adherence to sentinel lymph node MSKCC algorithm|Ergonomics of the two different surgical approach|Quality of life (QoL) at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery|Adherence to ESGO surgical Quality Index|Difference in overall survival and disease-free survival Female Not Applicable 566 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 5798 September 1, 2029

Fang, Q., et al. (2022). "Effect of peer support intervention on perinatal depression: A meta-analysis." General Hospital Psychiatry 74: 78-87.
	Background: To assess the effect of peer support on preventing or treating perinatal depression. Method(s): Eight databases (Wanfang, VIP, CNKI, CBM, Pubmed, Embase, PsycINFO, and Cochrane) were systematically searched for eligible randomized controlled trials from inception to July 2021. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed extraction form. Result(s): A total of 16 studies (including 3154 participants, peer support group: 1568, control group: 1586) were included in this meta-analysis. The intervention group (peer support) had significantly better effect on preventing or treating perinatal depression than the control group [SMD = -0.39, 95% CI (-0.54, -0.24), P < 0.00001, I2 = 78%]. The results of subgroup analyses showed that peer support interventions provided in the perinatal period [SMD = -0.51, 95% CI (-0.93, -0.09), P = 0.02] or only in the postpartum period could improve the depression of mothers [SMD = -0.44, 95% CI (-0.62, -0.26), P < 0.00001]. Face-to-face interventions [SMD = -0.28, 95% CI (-0.40, -0.15), P < 0.0001] and telephone/internet-based interventions [SMD = -0.73, 95% CI (-0.95, -0.50), P < 0.00001] were both effective for perinatal depression. As for form of intervention, the combination of individual and group sessions had the best effect on improving perinatal depression [SMD = -0.63, 95% CI (-1.04, -0.23), P = 0.002]. Peer support with the frequency of at least once a week had a significant effect on perinatal depression [SMD = -0.88, 95% CI (-1.32, -0.44), P < 0.0001]. Interventions with a length of <=3 months [SMD = -2.20, 95% CI (-3.35, -1.04), P = 0.0002] worked better than those lasting for 3-36 months [SMD = -1.64, 95% CI (-2.38, -0.90), P < 0.0001] in perinatal depression management. Peer support could improve perinatal depression both in low- and middle-income countries [SMD = -0.70, 95% CI (-0.95, -0.45), P < 0.00001] and high-income countries [SMD = -0.15, 95% CI (-0.28, -0.02), P = 0.03]. Conclusion(s): Providing peer support during the perinatal period or only postpartum period, using Internet or telephone approaches, a combination of group and individual, at least once a week can be regarded as an effective measure to manage perinatal depression.Copyright © 2021

Fang Qing, Y., et al. (2023). "Evidence for the role of multidisciplinary team care in people with pelvic pain and endometriosis: A systematic review." The Australian & New Zealand Journal of Obstetrics & Gynaecology.
	Background: Endometriosis is a chronic, inflammatory condition characterised by the presence of endometrial-like tissue outside the uterine cavity. Given the multi-system nature of the disease and the potential for significant negative impact on quality of life, there has been a long-standing recognition of the need for multidisciplinary care for people with endometriosis. However, there is paucity to the data supporting this approach, and much of the evidence is anecdotal.; Aim: This systematic review aims to describe recent evidence-based models and patient-centred perspectives of multidisciplinary care for endometriosis, to improve understanding of the role of an integrated, multidisciplinary team in effectively addressing patients' care needs.; Materials and Methods: PubMed, Medline, Embase and Web of Science were searched for relevant articles published between 1 January 2010 to 7 July 2022.; Results: Nineteen studies met the inclusion and exclusion criteria and pinpointed a multidisciplinary team consisting of gynaecologists, pain specialists, nurses, physiotherapists, psychologists, sex therapists, nutritionists, complementary medicine practitioners, and social workers to be most commonly utilised in holistically managing people with pelvic pain and endometriosis. Furthermore, patient perspectives on care highlighted the need for reliable information, respect and validation of experiences or preferences, discussion of long-term treatment plans and social and emotional supports.; Conclusion: The trend for multidisciplinary team care for people with endometriosis is growing. Further consumer-driven clinical studies and outcome evaluations need to be conducted to determine the effect of multidisciplinary care on improvements to quality of life for people living with endometriosis and or pelvic pain. (© 2023 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Fang-fang, H., et al. (2022). "Study on moxibustion in the treatment of uterine fibroids and its related brain changes based on rs-fMRI: a protocol for a systematic reviews and meta-analysis."
	
Fani, M., et al. (2023). "The effect of trunk-stabilizing muscles training in women with stress urinary incontinence: A Randomized Controlled Trial." PM & R : the journal of injury, function, and rehabilitation.
	INTRODUCTION: There is little evidence regarding the effect of trunk-stabilizing muscles training on the improvement of stress urinary incontinence (SUI) symptoms. OBJECTIVE: To investigate the effect of trunk-stabilizing muscles training on trans-abdominal ultrasonography (TAUS) and clinical urological indices, and on the quality of life (QoL) in women with SUI. DESIGN: Randomized controlled trial. SETTING: A university hospital. PARTICIPANTS: Forty-six women with SUI, aged 20-55 years, were randomly assigned to experimental (n =23) and control group (n =23). INTERVENTIONS: The experimental group performed trunk stabilization exercises according to the Sapsford protocol, while the control group performed pelvic floor muscle (PFM) exercises for eight weeks. MAIN OUTCOME MEASURES: The primary outcome measure was bladder base displacement (BBD), assessed by TAUS during PFM contraction (PFMC), Valsalva, and abdominal curl. The secondary outcome measures were PFM strength, the severity of urinary incontinence (UI), voiding diary, and QOL, assessed by the Modified Oxford Grading System, the severity index, frequency chart, and lower urinary tract symptoms-QOL questionnaire respectively. All variables were assessed at baseline and after 8-weeks of interventions. RESULTS: The interaction of group and time wasn't significant for BBD during PFMC (p=0.98), Valsalva (p=0.28), abdominal curl (p=0.34), and secondary variables (p>0.05). The main effect of time was significant in both groups for BBD during PFMC, PFM strength, the severity of UI, voiding diary, and QoL (p<0.001), with effect size (d) of 0.30, 0.80, 2.05, 1.07, 1.03 in the control; and 0.49, 0.52, 1.75, 0.66, 0.88 in the experimental group respectively. The main effect of the group wasn't significant for BBD during PFMC (p=0.68), Valsalva (p=0.22), abdominal curl (p=0.53), and secondary variables (p>0.05). CONCLUSIONS: Trunk-stabilizing muscles training and PFM exercise are equally effective in the improvement of PFM function, UI symptoms, and QOL in women with SUI. Both methods can be used interchangeably by physical therapists. This article is protected by copyright. All rights reserved.

Fankam Aimé, G., et al. (2023). "Guttiferone BL from the Fruits of Allanblackia gabonensis Induces Mitochondrial-Dependent Apoptosis in PA-1 Ovarian Cancer Cells." BioMed Research International 2023: 8981430.
	Despite the recent advancement of treatment strategies, cancer ranks 2 nd among the causes of death globally. Phytochemicals have gained popularity as an alternate therapeutic strategy due to their nontoxic nature. Here, we have investigated the anticancer properties of guttiferone BL (GBL) along with four known compounds previously isolated from Allanblackia gabonensis . The cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The study was extended for the assessment of the effect of GBL in PA-1 cells apoptosis induction, cell cycle distribution, and change in mitochondrial membrane potential using flow cytometry, Western blot analysis, and real-time PCR. Among the five tested compounds, GBL displayed significant antiproliferative effects against all tested human cancer cells (IC 50 < 10 μ M). Moreover, GBL exhibited no significant cytotoxicity towards normal ovarian epithelial cell line (IOSE 364) up to 50 μ M. GBL induced sub-G 0 cell cycle arrest and significant upregulation of cell cycle regulatory proteins of ovarian cancer cell PA-1. Furthermore, GBL induced its apoptosis as depicted by the accumulation of cells both at the early and late apoptotic phase in Annexin V/PI assay. In addition, it decreased the PA-1 mitochondrial membrane potential and promoted upregulation of caspase-3, caspase-9, and Bax and downregulation of Bcl-2. GBL also showed a dose-dependent inhibition of PA-1 migration. Altogether, this study reveals that guttiferone BL, studied herein for the first time, exhibits efficient antiproliferative activity by the induction of apoptosis through the mitochondrial-dependent pathway. Its investigation as a therapeutic agent against human cancers especially ovarian cancer should be envisaged.; Competing Interests: The authors declare that they have no known competing interests. (Copyright © 2023 Aimé Gabriel Fankam et al.)

Fanourgiakis, A., et al. (2022). "Manchester-Fothergill Operation Compared to Vaginal Hysterectomy for Uterine Prolapse." International Urogynecology Journal 33(Supplement 2): S432-S433.
	Introduction: Symptomatic uterine prolapse is a common indication for pelvic floor surgery. The surgical options include uterine conserving procedures or hysterectomy. Recently, uterine conserving surgery has become limited due to the reported complications of synthetic meshes and many women are declining mesh implants. The optimal choice of procedure should be based on low recurrence rates and complications. Although there are several surgical methods described to conserve the uterus, there is a lack of strong evidence supporting a superior technique. Objective(s): Our aim was to evaluate the effectiveness and peri/post operative outcomes of the uterine-sparing Manchester-Fothergill repair (MR) compared to vaginal hysterectomy (VH), which is the most common procedure for uterine prolapse. The impact of severity of prolapse and increased BMI (>30) on the surgical outcome was also assessed. Method(s): We have retrospectively evaluated the data from the perioperative period and the 6-week follow-up appointment of 48 patients, who underwent a Manchester repair in a single centre from 2010 to 2018. All procedures were performed by the same surgeon. Result(s): The mean age was 62.3 years. 95% of patients were multiparous and 89.6% post-menopausal. The mean BMI was 27.8. 89.6% presented with concurrent cystocele and 83.3% with rectocele. The mean operating time was 105+/-22 minutes and the average hospital stay was 2.51 days. 2 patients did not attend the post-operation follow- up review. 5 patients (10.4%) had EBL>1000ml, none had organ injury and 1 (2.1%) patient required antibiotics due to post-operative infection. In follow-up review, cervical stenosis was noted in 3 (6.3%) patients and recurrence of apical prolapse in only 1 (2.1%) patient. We identified 11 patients with severe prolapse (ie stage 3 and 4). Of those, 3 (27.3%) had major haemorrage >1000ml [RR 4.2, 95%CI (0.77-22.4), p 30, major haemorrhage occurred in 2 (15.4%). The mean operating time (103 minutes) and average hospital stay (3.5 days) did not differ significantly from patients with BMI below 30. No patients had recurrence in follow-up. In comparison, the literature on VH suggests a 2.9-10% risk of major bleeding, 5-13% risk of infection. 0.2-2% risk of bladder or ureteric injury. The recurrence rates of apical prolapse in the literature range from 1-13% for VH and 0.3-9.5% for MR. Conclusion(s): The Manchester repair should be considered a good alternative to VH, even for stage 3-4 prolapse. Our data demonstrates good medium-term results and low complication rates. Additionally, the uterus is preserved, which is an important consideration for many women. Severe prolapse and high BMI appear to increase the risk of intra-operative blood loss but do not affect the recurrence rate. The sample size, however, was small and further longer term follow up data will be collected.

Farahbod, F., et al. (2022). "Effectiveness of phosphodiesterase type 5 inhibitors on the treatment of thin endometrium and pregnancy outcomes: An systematic review." Journal of Endometriosis and Pelvic Pain Disorders 14(3): 132-142.
	Phosphodiesterase type 5 (PDE5) inhibitors are thought to play a role in increasing endometrial thickness and increasing the success rate of pregnancy outcomes. This study was done to investigate the effects of PDE5 inhibitors on infertile women with thin endometrium and pregnancy outcomes. In this systematic review, all randomized controlled trials (RCTs) and observational studies were retrieved from databases including Institute for Scientific Information (ISI), PubMed, and Scopus by interesting keywords. A checklist was designed to collect necessary data and pregnancy outcomes, and the required items were recorded. PDE5 inhibitors through various mechanisms such as induction of vasodilatory effect through the effect on NO/cGMP signaling on vascular smooth muscle, through regulating cells proliferation and induction angiogenesis by increasing the expression of tumor suppressor factor (p53), and vascular endothelial growth factor A (VEGF-A) and downregulating inflammation by downregulating proinflammatory cytokines, affect endometrial thickness that eventually increases and pregnancy outcomes. Although PDE5s inhibitors increase endometrial thickness by different mechanisms, especially in women with thin endometrial, this does not necessarily mean that they induce a positive effect in all situations. However, their positive effects on pregnancy outcome may be affected by the time of administration, type of infertility treatment, underlying diseases such as pelvic disorders and inflammation. So in this regard, there are still ambiguous aspects that required further RCTs study in this area.Copyright © The Author(s) 2022.

Farewell, C. V., et al. (2021). "Maternal mental health and early childhood development: Exploring critical periods and unique sources of support." Infant mental health journal 42(4): 603-615.
	BACKGROUND: The objective of this study was to explore associations between maternal depression and anxiety during early sensitive periods, child social-emotional and behavioral problems and the moderating roles of financial, instrumental, and partner emotional support. METHODS: Analyses was conducted using data from the Fragile Families and Child Wellbeing Study. Hierarchical linear regression modeling was used to explore associations between maternal depression and anxiety at 1- and 3-years postpartum, three unique types of social support, and childhood behavioral problems at 5-years of age (n = 2,827). RESULTS: Mothers who were depressed at one or both timepoints, compared to nondepressed mothers, reported higher externalizing behavioral problems scores of 1.96 and 2.90, and internalizing behavioral problems scores of 1.16 and 2.20, respectively, at 5-years of age (both p < .01), after controlling for covariates. Financial, instrumental, and partner emotional support were independently and inversely associated with behavioral problems (p < .05); however, none of these types of support moderated the relationship between maternal depression and behavioral problems, after controlling for covariates. IMPLICATIONS: Promoting maternal mental health as well as different sources of support throughout the first five years of life, instead of one critical period, may help to reduce the burden of chronic disease in the next generation.

Farhud, D. D., et al. (2021). "In-Vitro Fertilization Impact on the Risk of Breast Cancer: A Review Article." Iranian Journal of Public Health 50(3): 438-447.
	BACKGROUND: Due to the increasing prevalence of infertility, the number of referrals to infertility treatment centers has also increased. Nowadays, assisted reproductive technology (ART), including in vitro fertilization (IVF), is a treatment for infertility or genetic problems. Considering the possible consequences of this method among women undergoing in vitro fertilization (IVF) and kids conceived by IVF, extensive research has been conducted in this regard. METHODS: Overall, 100 articles were entered into the study, and relevant articles were searched and extracted from PubMed, Springer, and Google Scholar databases. In IVF procedure, medications such as Clomiphene citrate and gonadotropins are used to stimulate and mature follicles and thus increase ovulation. RESULTS: There are conflicting opinions on this issue. Some findings report a slight increase in cancer risk for hormone-sensitive cancers including breast cancer. The long-term use of IVF medications can increase estrogen hormones and cause excessive expression of genes, resulting in an increased risk of breast cancer, which is one of the most frequent cancers among women. CONCLUSION: There are some risks to be aware of, which followed the hypothesis that long IVF treatment process may lead to breast cancer among IVF candidates. Furthermore, the risk of breast cancer may be increased in those women with a positive family history and related inherited genes. Therefore, women candidates for IVF should be informed of the probable implications of the reproductive therapy techniques.

Farid-Kapadia, M., et al. (2023). "Comparison of tumor-agnostic and tumor-specific clinical oncology trial designs: A systematic review and meta-analysis." Future Oncology 19(25): 1741-1752.
	Aim: To examine whether tumor-specific and tumor-agnostic oncology trials produce comparable estimates of objective response rate (ORR) in BRAF-altered cancers. Material(s) and Method(s): Electronic database searches were performed to identify phase I-III clinical trials testing tyrosine kinase inhibitors from 2000 to 2021. A random-effects model was used to pool ORRs. A total of 22 cohorts from five tumor-agnostic trials and 41 cohorts from 27 tumor-specific trials had published ORRs. Result(s): There was no significant difference between pooled ORRs from either trial design for multitumor analyses (37 vs 50%; p = 0.05); thyroid cancer (57 vs 33%; p = 0.10); non-small-cell lung cancer (39 vs 53%; p = 0.18); or melanoma (55 vs 51%; p = 0.58). Conclusion(s): For BRAF-altered advanced cancers, tumor-agnostic trials do not yield substantially different results from tumor-specific trials.Copyright © 2023 Roche Canada.

Farkas, W., et al. (2023). "Perioperative hormone treatment of endometriosis." Current opinion in obstetrics & gynecology 35(5): 434-439.
	Purpose of Review: The use of hormonally suppressive medication to reduce levels of reproductive hormones around the time of surgery is widely used in the management of endometriosis. This review summarizes the current evidence concerning the perioperative use of hormonal treatment in the management of endometriosis.; Recent Findings: European Society of Human Reproduction and Embryology (ESHRE) guidanceSurgical Outcomes and Complications of Laparoscopic Hysterectomy for Endometriosis: A Multicentre Cohort StudyPre and postsurgical medical therapy for endometriosis surgery. Cochrane 2020Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis. BJOG 2021.; Summary: The literature highlights the importance of hormonal treatment for symptom relief, reduced surgical complications and postoperative benefits, including a reduction in pain, disease recurrence and improved pregnancy rates. The treatment of endometriosis can be broadly categorized into medical, commonly using hormonal suppression medications and surgical, in which endometriosis tissue is excised or ablated. This review aims to outline current management strategies and examines the relationship between the two treatment modalities. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Farley John, H., et al. (2022). "A phase II evaluation of temsirolimus with carboplatin and paclitaxel followed by temsirolimus consolidation in clear cell ovarian cancer: An NRG oncology trial." Gynecologic Oncology 167(3): 423-428.
	Objective: The primary objective of the study was to estimate the 12-month progression-free survival (PFS) for carboplatin/paclitaxel + temsirolimus in women with newly diagnosed clear cell ovarian cancer (CCOC), compared to historical controls in this patient population.; Methods: Patients with Stage III or IV CCOC were treated with Paclitaxel 175 mg/m2 on Day 1, Carboplatin AUC 6 Day 1, and temsirolimus (CCI-779) 25 mg IV Days 1 and 8 every 3 weeks for Cycles 1-6 or disease progression, followed by consolidation therapy with temsirolimus 25 mg Days 1, 8, and 15 every 3 weeks cycles 7-17 or until disease progression.; Results: Ninety patients were accrued to the study: 45 in the US and Korea (US/Korea) and 45 in Japan. Twenty-two percent received ≤6 cycles of therapy while 28% completed all 17 cycles of chemotherapy. Median PFS (OS) was 11 (23) months for US/Korea and 12 (26) months for Japan. In the US, none of suboptimally debulked patients had PFS >12 months, and 49% of optimal patients did, compared to 25% and 59% in Japan. Most common grade 3-4 adverse events were neutropenia, leukopenia, anemia, thrombocytopenia, hypertension, hypertriglyceridemia, and oral mucositis.; Conclusion: The carboplatin/paclitaxel + temsirolimus regimen was well tolerated. In optimally debulked patients, 54% had a PFS >12 months. This regimen did not statistically significantly increase PFS at 12 months compared to historical controls. No statistically significant differences in PFS or OS were observed between US/Korea vs Japan, or Asians vs non-Asians.; Competing Interests: Conflicts of interest With the exception of Dr. Gershenson, Secord and Yonemari (see details below), the co-authors have no conflicts of interest to declare. Dr. David Gershenson who reports grants received from Novartis in support of GOG-0281 to his Institution. Dr. Gershenson also reports that he received personal payments from Elsevier and UpToDte as well as personal consulting fees received from Genentech and Springworks. Dr. Gershenson also reports receiving stocks from Biogen, Inc., Johnson & Johnson and Bristol Myers Squibb. Dr. Secord reports receiving grant funding from the National Cancer Trial Network to her institution. She also reports clinical trial grants from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Clovis, Eisai, Immutep Ltd., Merck, Oncoquest PharmaMar, Roche/Genentech, Seagen Inc., Tesaro/GSK and VBL Therapeutics. Dr. Secord additionally reports receiving consulting fees from AstraZeneca, Clovis, Cordgenics, Eisai, Merck and Myriad as well as support for travel to attend Advisory Board meetings from AbbVie, Eisai and Tesaro. Dr. Secord served on the SGO Board of Directors, GOG Foundation Board of Directors and AAOGF Board of Trustees. Further to that, Dr. Secord reports receiving an experimental agent from Genentech for preclinical studies and participated on uncompensated advisory boards for Abbvie, Aravive, GSK, Regeneron and Tesaro as well as uncompensated Clinical Trial Steering Committees for Genentech/Roche, VBL Therapeutics and Oncoquest. Dr. Yonemori reports he received consulting fees from Novartis and Eisai. He also received honoraria for lectures from AstraZeneca, Eisai, Chugai, Takeda, Pfizer, and Eli Lilly. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Farrell, R., et al. (2022). "Clinical Trial Protocol for HyNOVA: Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian, fallopian tube and primary peritoneal cancer (ANZGOG1901/2020)." Journal of Gynecologic Oncology 33(1): e1.
	Background: Ovarian cancer is the most lethal gynecological cancer, causing over 200,000 deaths worldwide in 2020. Initial standard treatment for primary ovarian cancer is optimal cytoreductive surgery (CRS) preceded and/or followed by intravenous platinum-based chemotherapy. However, most women develop recurrence within the peritoneal cavity and die of disease. Results of the OVIHIPEC 1 trial (2018) showed improved survival of 34% when hyperthermic intraperitoneal chemotherapy (HIPEC) was given immediately following interval-CRS in women with stage III disease. However, it is unknown if the effect of HIPEC is due to hyperthermia, one extra cycle of intraperitoneal (IP) chemotherapy, or other factors. There is also concern that hyperthermia might be associated with an increase in adverse events (AEs) due to a heightened systemic inflammatory response. HyNOVA is a seamless, multi-stage randomized study that attempts to answer these questions by comparing HIPEC to normothermic intraperitoneal chemotherapy (NIPEC), focusing on safety (stage 1), then assessing activity (stage 2) and effectiveness (stage 3). In this initial study, we hypothesize that NIPEC will result in a lower rate of severe AEs compared to HIPEC.; Methods: This initial stage of HyNOVA is a phase II study of 80 women with International Federation of Gynaecology and Obstetrics stage III epithelial ovarian cancer, with at least stable disease following 3-4 cycles of neoadjuvant chemotherapy, achieving interval-CRS to <2.5 mm residual disease. Participants are randomized 1:1 to receive IP cisplatin 100 mg/m² for 90 minutes either as HIPEC, heated to 42°C (41.5°C-42.5°C), or NIPEC, at 37°C (36.5°C-37.5°C). The primary outcome is the proportion of AEs ≥ grade 3 occurring within 90 days. Secondary outcomes are AE of interest, surgical morbidity, patient reported outcomes, resource allocation, feasibility, progression-free survival and overall survival. AEs are measured using both CTCAE v5.0 and Clavien-Dindo classification, particularly infection, pain, bowel dysfunction, and anemia. Tertiary outcomes are potential predictive biomarkers measured before and after HIPEC/NIPEC including circulating cell-free tumor DNA, tissue factors, and systemic inflammatory markers. There are 4 participating Australian sites with experience in CRS and HIPEC for peritoneal malignancy. HyNOVA is funded by an MRFF grant (APP1199155).; Trial Registration: ANZCTR Identifier: ACTRN12621000269831.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Farvid Maryam, S., et al. (2020). "Fiber consumption and breast cancer incidence: A systematic review and meta-analysis of prospective studies." Cancer 126(13): 3061-3075.
	Background: Associations between fiber intake and breast cancer risk have been evaluated in prospective studies, but overall, the evidence is inconsistent. The authors performed a systematic review and meta-analysis of prospective studies to investigate the relation between intake of total and types of fiber with breast cancer incidence.; Methods: The MEDLINE and Excerpta Medica dataBASE (EMBASE) databases were searched through July 2019 for prospective studies that reported on the association between fiber consumption and incident breast cancer. The pooled relative risk (RR) and 95% confidence intervals (95% CI) were estimated comparing the highest versus the lowest category of total and types of fiber consumption, using a random-effects meta-analysis.; Results: The authors identified 17 cohort studies, 2 nested case-control studies, and 1 clinical trial study. Total fiber consumption was associated with an 8% lower risk of breast cancer (comparing the highest versus the lowest category, pooled RR, 0.92; 95% CI, 0.88-0.95 [I 2 = 12.6%]). Soluble fiber was found to be significantly inversely associated with risk of breast cancer (pooled RR, 0.90 [95% CI, 0.84-0.96; I 2 = 12.6%]) and insoluble fiber was found to be suggestively inversely associated with risk of breast cancer (pooled RR, 0.93 [95% CI, 0.86-1.00; I 2 = 33.4%]). Higher total fiber intake was associated with a lower risk of both premenopausal and postmenopausal breast cancers (pooled RR, 0.82 [95% CI, 0.67-0.99; I 2 = 35.2%] and pooled RR, 0.91 [95% CI, 0.88-0.95; I 2 = 0.0%], respectively). Furthermore, the authors observed a nonsignificant inverse association between intake of total fiber and risk of both estrogen and progesterone receptor-positive and estrogen and progesterone receptor-negative breast cancers.; Conclusions: A random-effects meta-analysis of prospective observational studies demonstrated that high total fiber consumption was associated with a reduced risk of breast cancer. This finding was consistent for soluble fiber as well as for women with premenopausal and postmenopausal breast cancer. (© 2020 American Cancer Society.)

Farzaneh, F., et al. (2022). "THE VALUE OF NON HORMONAL HERBAL COMPLEMENTARY ON REDUCING MENOPAUSAL HOT FLASHES." International Journal of Gynecological Cancer 32: A215.
	Objectives Hot flashes is a bothering symptom in perimenopause women as well as in women after cancer treatment. Present study aimed to investigate the effects of a non‐hormonal herbal complementary(NHHC) in the treatment of hot flashes. Methods This study is the preliminary result of an ongoing large clinical research assessing the effect of NHHC on reducing hot flashes particularly when hormonal treatment is contraindicated. A randomized, double‐blind, placebo‐controlled clinical trial was performed on 70 postmenopause women with symptoms of hot flashes (no history of cancer). The cases(n=35) were given 2 capsules/daily of EstroG‐100 (extracts of Cynanchum wilfordii Hemsley, Phlomis umbrosa Turczaninow, Angelica gigas Nakai) for 12 weeks. The controls( n=35) were given placebo. The consent form, demographic questionnaire were completed. The severity of hot flashes recorded weekly for 12 weeks. Statistical tests were performed using SPSS 22.0. Results The mean age was 51.1±0.4 and 50.3±0.4 in cases and controls respectively. The mean duration of menopause was < 2 years. No significant differences found in the demographic factors. Among all the laboratory tests, just the Alkaline phosphatase value in the cases was significantly higher than the controls (p‐value = 0.047). In the cases the reduction of the severity of hot flashes at 30, 60, and 90 days after treatment and the trend of reduction, were significantly reduced(P<0.001). The severity of hot flashes in the control group did not change significantly during the study. Conclusions In this study the use of herbal extract (EstroG‐ 100) significantly reduced the severity of hot flashes in postmenopause women, without significant adverse effects.

Farzaneh, R., et al. (2021). "The Effect of Hypnosis Therapy on Dysmenorrhea: A Systematic Review." PROSPERO International prospective register of systematic reviews.
	
Fasanghari, M., et al. (2023). "The Effect of Aromatherapy Massage with Lavender Oil on the Severity of Primary Dysmenorrhea among University Students: a Randomized Clinical Trial." Journal of midwifery & reproductive health 11(1): 3592‐3601.
	
Fata, S. and M. A. Tokat (2021). "Does Hypnofertility-Based Nursing Care Affect Cortisol Levels, Fertility Preparedness, and Pregnancy Outcomes in Women Undergoing In Vitro Fertilization? A Randomized Controlled Trial." Biological Research for Nursing 23(3): 418-429.
	This study used Hypnofertility-based interventions to determine whether these interventions would lead to increased fertility preparedness and pregnancy outcomes and decreased cortisol levels in women undergoing In Vitro Fertilization (IVF) treatment. This randomized, controlled, prospective study was conducted from November 2017 through March 2019 in 61 Turkish women with unexplained infertility (intervention group: 30, control group: 31). Hypnofertility-based nursing care included affirmations, visualization, imagination, and relaxation from the first day of treatment until the day of the pregnancy test. The Fertility Preparedness Scale, a saliva sample for cortisol level, and the pregnancy test results were used for data collection. Hypnofertility-based nursing care decreased the cortisol levels of women in the intervention group compared to that in the control group (p = 0.00). Though fertility preparedness was higher in the intervention group, the difference was not statistically significant (p = 0.13). Although interventions relieved the women during the treatment process, there was no anticipated effect on pregnancy outcomes (p = 0.75). Hypnofertility-based nursing care significantly reduce the cortisol levels, suggesting that the intervention helped women relax.

Fatebenefratelli, I. C. S. G. d. D. (2022). Exposures to Perinatal Adverse Experiences: Multimodal Omics Signature of Stress Vulnerability and Resilience and Preventive Strategies.
	[Non-randomized, open label; 4 locations; ] The study aims at identifying: specific biological and molecular alterations associated with development of depression in pregnancy or risk of it. specific biological and molecular alterations due to exposure to maternal depression in utero that are still present in the offspring, that could possibly mediate the development of negative outcomes, and which are the possible clinical moderators of the associated risk; whether antidepressant therapies prescribed by personal physician and the use of digital tools can have a preventive effect in the transmission of the risk from mothers to babies and in the development of depressive symptoms in high-risk pregnant women; In order to achieve these, 80 pregnant women with depression, 80 at high-risk and 80 controls will be recruited and clinically monitored over pregnancy and postpartum along with their babies, specifically at these timepoints: 25th and 32nd weeks of gestation, 1 week postpartum, 4 weeks postpartum, 8 weeks postpartum, 12 months postpartum. Women, based on their clinician choice, will receive antidepressants and will be provided with a smartphone app to monitor them, using a combination of personalised, daily self-reported assessments and sensors for passive data collection to cover mental and physical health. Blood and saliva samples from pregnant women will be collected at the 25th and 32nd week of gestation to perform biological analyses. Saliva samples from babies will be collected at 8 weeks and 12 months postpartum to perform biological analyses. Clinical and psychological data will be collected from women at all timepoints.

Fathy, A., et al. (2023). "The Effectiveness of using Letrozole prior Tomisoprostol Versus Misoprostol alone for Successful Induction of missed Abortion: a Randomized Controlled Trial." Research journal of pharmacy and technology 16(5): 2233‐2238.
	Objective: To evaluate the efficacy of medical abortion induction when Letrozole and misoprostol are combined vs when misoprostol is used alone. Methods: It was intended for 150 women to participate in a randomized controlled experiment. They were split into two groups at random, each with 75 people. While the control group (misoprostol alone group) only got misoprostol, the case group (letrozole group) received pretreatment letrozole 12.5mg for two days. According to American College of Obstetrics and Gynecology (ACOG) recommendations based on gestational Age, misoprostol was administered to both groups in the following dosages: 800mg sublingually in a single dose during the first trimester and 400mg sublingually every 3 hours for up to 5 doses during the second trimester. Results: 137 women in all, 69 of whom received Letrozole and 68 of whom received misoprostol alone. Complete abortions were recorded in 96 instances (70.07%), 51 of which were associated with Letrozole (73.9%) and 45(66.2%) with misoprostol alone (P=0.32). However, the case and control groups had corresponding mean expulsion start times of 7.51.8 hours and 8.31.5 hours. This suggests that the case group had an ejection that began much sooner (P=0.003). Conclusion: The current study found that a combination of misoprostol with Letrozole did not lead to a significantly higher rate of complete abortion if compared with misoprostol alone among women with missed abortion up to 20 weeks gestation. It only significantly shortened the interval to the initiation of expulsion.

Fathy, M., et al. (2021). "Literature review of the outcome of and methods used to improve transperineal repair of rectocele." World journal of gastrointestinal surgery 13(9): 1063-1078.
	BACKGROUND: Rectocele is commonly seen in parous women and sometimes associated with symptoms of obstructed defecation syndrome (ODS). AIM: To assess the current literature in regard to the outcome of the classical transperineal repair (TPR) of rectocele and its technical modifications. METHODS: An organized literature search for studies that assessed the outcome of TPR of rectocele was performed. PubMed/Medline and Google Scholar were queried in the period of January 1991 through December 2020. The main outcome measures were improvement in ODS symptoms, improvement in sexual functions and continence, changes in manometric parameters, and quality of life. RESULTS: After screening of 306 studies, 24 articles were found eligible for inclusion to the review. Nine studies (301 patients) assessed the classical TPR of rectocele. The median rate of postoperative improvement in ODS symptoms was 72.7% (range, 45.8%-83.3%) and reduction in rectocele size ranged from 41.4%-95.0%. Modifications of the classical repair entailed omission of levatorplasty, addition of implant, concomitant lateral internal sphincterotomy, changing the direction of plication of rectovaginal septum, and site-specific repair. CONCLUSION: The transperineal repair of rectocele is associated with satisfactory, yet variable, improvement in ODS symptoms with parallel increase in quality-of-life score. Several modifications of the classical TPR were described. These modifications include omission of levatorplasty, insertion of implants, performing lateral sphincterotomy, changing the direction of classical plication, and site-specific repair. The indications for these modifications are not yet fully clear and need further prospective studies to help tailor the technique to rectocele patients.

Fatih, Ö., et al. (2023). "Effectiveness of physical therapy on pain severity, disability and quality of life on lumbopelvic pain pain among postpartum: Systematic Review and Meta-analysis."
	
Fatima, R. and A. Hania (2022). "Predisposition of Early Maladaptive Schemas and Postpartum Depression during COVID-19 Crisis: Mediation of Mindfulness." Psychiatria Danubina 34(1): 148-156.
	BACKGROUND: Past studies provide crucial evidence that pregnancy and childbirth increase the risk of emotional vulnerability and instability. Current research intends to explore the role of early maladaptive schemas and mindfulness as determinants of postpartum depression for expecting mothers during COVID-19 pandemic. METHOD: The data was collected from 170 expecting mothers who conceived and gave birth during the COVID-19 pandemic. Edinburgh postnatal depression scale, the young schema questionnaire-SF 75 items, and the Kentucky inventory for mindfulness scale were administered. RESULTS: Results discovered that mindfulness partially mediated the relationship between three kinds of early maladaptive schemas and postpartum depression. CONCLUSION: Mindfulness-based control techniques can be considered to buffer the impact of the early maladaptive schemas on postpartum depression, for mothers who give birth during any challenging time.

Faucher, S., et al. (2024). "Investigating the role of the pelvic floor muscles in sexual function and sexual response: a systematic review and meta-analysis." Journal of Sexual Medicine 21(3): 217-239.
	Introduction: The pelvic floor muscles (PFMs) have been suggested to play a key role in sexual function and response in women. However, syntheses of the evidence thus far have been limited to interventional studies in women with pelvic pain or pelvic floor disorders, and these studies have failed to fully capture the involvement of the PFMs in a broader population. Aim(s): We sought to appraise the evidence regarding the role of the PFMs in sexual function/response in women without pelvic pain or pelvic floor disorders. More specifically, we examined the following: (1) effects of treatment modalities targeting the PFMs on sexual function/response, (2) associations between PFM function and sexual function/response, and (3) differences in PFM function between women with and those without sexual dysfunction. Method(s): We searched for all available studies in eight electronic databases. We included interventional studies evaluating the effects of PFM modalities on sexual outcomes, as well as observational studies investigating the association between PFM function and sexual outcomes or the differences in PFM function in women with and those without sexual dysfunction. The quality of each study was assessed using the Mixed Methods Appraisal Tool. Estimates were pooled using random-effects meta-analyses whenever possible, or a narrative synthesis of the results was provided. Main outcomes: The main outcomes were sexual function (based on a questionnaire)/sexual response (based on physiological test), and PFM function (assessment of the PFM parameters such as strength and tone based on various methods). Result(s): A total of 33 studies were selected, including 14 interventional and 19 observational studies, most of which (31/33) were deemed of moderate or high quality. Ten out of 14 interventional studies in women with and without sexual dysfunctions showed that PFM modalities had a significant effect on sexual function. Regarding the observational studies, a meta-analysis revealed a significant moderate association between PFM strength and sexual function (r = 0.41; 95% CI, 0.08-066). Of the 7 observational studies performed to assess sexual response, all showed that the PFMs were involved in arousal or orgasm. Conflicting results were found in the 3 studies that evaluated differences in PFM function in women with and those without sexual dysfunction. Clinical implications: Our results highlight the contribution of the PFMs in sexual function/response. Strengths and limitations: One strength of this review is the inclusion of a broad range of study designs and outcomes, allowing a thorough synthesis of evidence. However, interpretations of these data should consider risk of bias in the studies, small sample sizes, and the absence of control/comparison groups. Conclusion(s): The findings of this review support the involvement of the PFMs in sexual function/response in women without pelvic pain or pelvic dysfunction. Well-designed studies should be performed to further investigate PFM modalities as part of the management of sexual dysfunction.Copyright © The Author(s) 2024.

Faure-Conter, C., et al. (2023). "Extracranial germ cell tumours in children and adolescents: Results from the French TGM13 protocol." Pediatric blood & cancer 70(3): e30117.
	Background: Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more.; Procedure: Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine-bleomycin-cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide-cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.; Results: One hundred fifteen patients were included: median age of 12.8 years (0.4-18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80-92) and 95% (89-98), respectively (median follow-up: 3.5 years, range: 0.2-5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84-93), 5-year OS 93% (89-95), p = .561). The 5-year EFS were 93% (95% CI: 80-98), 88% (71-95) and 79% (62-90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p = .02) according to the risk groups: 90% (66-97), 64% (30-85), 95% (72-99) and 87% (74-94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003-1.007).; Conclusion: Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy. (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Fauser, D., et al. (2023). "Work-Related Medical Rehabilitation for Cancer Patients Receiving Non-postacute Rehabilitation A Post-hoc Subgroup Analysis." Deutsches Arzteblatt international 120(49): 841-842.
	
Favilli, A., et al. (2023). "Impact of FIGO type 3 uterine fibroids on in vitro fertilization outcomes: A systematic review and meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 163(2): 528-539.
	Background: The effect of FIGO (the International Federation of Gynecology & Obstetrics) type 3 myomas on in vitro fertilization (IVF) is uncertain.; Objectives: To evaluate whether FIGO type 3 myomas affect IVF outcomes, through a systematic review and meta-analysis (CRD42022379700).; Search Strategy: Electronic databases were searched until November 15, 2022.; Selection Criteria: Studies evaluating the effects of FIGO type 3 myomas on IVF outcome.; Data Collection and Analysis: Pooled results were expressed as odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed using Higgins I 2 . Sources of heterogeneity were explored with sensitivity and subgroup analyses.; Main Results: In total, 1020 patients were included: 324 with FIGO type 3 myomas and 696 controls (without myomas). A pooled data analysis showed a significantly lower live birth rate (OR 2.16, 95% CI 1.55-3.01, I 2 = 0%, P < 0.00001), clinical pregnancy rate (OR 2.06, 95% CI 1.52-2.81, I 2 = 0%, P < 0.00001), and implantation rate (OR 1.77, 95% CI 1.35-2.32, I 2 = 0%, P < 0.00001) in women with untreated myomas compared with controls. The number and size of fibroids correlated with a worsening of IVF outcomes.; Conclusions: FIGO type 3 myomas are significantly associated with a lower implantation rate, cumulative pregnancy rate, and live birth rate. Furthermore, their deleterious effect on the outcome of IVF increases further with increasing size and number. Nevertheless, no firm conclusions could be drawn about the potential benefits of surgery for FIGO type 3 uterine fibroids on IVF outcomes. (© 2023 International Federation of Gynecology and Obstetrics.)

Favilli, A., et al. (2021). "Risk factors for non-adherent retained placenta after vaginal delivery: a systematic review." BMC Pregnancy and Childbirth 21(1): 268.
	Background: Retained placenta represents a cause of maternal morbidity and mortality affecting 0.5-3% of all vaginal deliveries. The unpredictability of this condition makes difficult to develop predictive and preventive strategies to apply in clinical practice. This analysis collected and analyzed all known risk factors related to this obstetric complication.; Methods: A systematic literature review for all original research articles published between 1990 and 2020 was performed. Observational studies about retained placenta risk factors published in English language were considered eligible. Conference abstracts, untraceable articles and studies focused on morbidly adherent placenta were excluded. The included articles were screened to identify study design, number of enrolled patients and retained placenta risk factors investigated. All stages of the revision followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.; Results: Thirty-five studies met the inclusion criteria. The reported retained placenta prevalence ranged from 0.5 to 4.8%. Maternal age, previous cesarean sections, previous dilation and curettage, previous retained placenta, labor induction, resulted as the most recurrent, independent risk factors for retained placenta. Previous estro-progestins therapy, morphological placental features (weight, shape, insertion of umbilical cord, implantation site), endometriosis, Assisted Reproductive Technologies, Apgar score are fascinating new proposal risk factors.; Conclusions: Old and new data are not enough robust to draw firm conclusions. Prospective and well-designed studies, based on a well agreed internationally retained placenta definition, are needed in order to clarify this potential dramatic and life-threatening condition.

Favre, G., et al. (2021). "Sentinel lymph-node biopsy in early-stage cervical cancer: the 4-year follow-up results of the senticol 2 trial." International Journal of Gynecological Cancer 31(SUPPL 1): A60.
	Introduction/Background∗ Senticol 2 is a randomized multicenter trial in the treatment of early‐stage cervical cancer patients. The aim of the Senticol 2 study was to compare the effect of sentinel‐lymph‐node biopsy (SLNB) to that of SLNB + pelvic lymphadenectomy (PLND), and to determine the postoperative lymphati Methodology In the Senticol 2 trial, patients underwent a laparoscopy with a sentinel‐node‐detection procedure and were randomized into two groups, namely: Group A, in which participants received SLNB, and Group B, in which participants received SLNB + PLND. Patients with an intra‐operative macroscopically suspicious lymph node, were given a frozen‐section evaluation and were randomized only if the results were negative. All of the patients received follow up with a clinical examination at 1, 3, and 6 months after surgery, and then every 3‐4 months after that. The median follow up was 51 months (4 years and 3 months). Result(s)∗ Disease‐free survival after 4 years for the SLNB group and the SLNB + PLND group were 89.51% and 93.1% (p = 0.53), respectively. The only statistical factor associated with recurrence in the univariate analysis was the adjuvant radiotherapy. No other factors, including the age of the patients, histological type, tumor size, lymph vascular space invasion (LVSI), and positive nodal status, were significant in the univariate or multivariate analyses. The overall survival rates after 4 years in the SLNB and SLNB + PLND groups were 95.2% and 96% (p = 0.97), with five and four deaths, respectively. The univariate and multivariate analyses did not find any prognostic factors. Conclusion∗ This randomized study confirmed the results of the Senticol 1 study and supports the sentinel lymph node (SLN) technique as a safe technique for use in patients with early‐stage cervical cancer treated with SLNB only. Diseasefree survival after 4 years was similar in patients treated with SLN biopsy and patients who underwent a lymphadenectomy.

Fealy, S., et al. (2019). "The Support for New Mums Project: A protocol for a pilot randomized controlled trial designed to test a postnatal psychoeducation smartphone application." Journal of Advanced Nursing 75(6): 1347-1359.
	Aim: To report a pilot trial protocol for testing the effectiveness of the Support for New Mums smartphone application in a cohort of first-time mothers.; Design: A pilot/feasibility randomized controlled trial using a two-group pre-test and repeated post-test design.; Method: This protocol follows the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) guidelines. The Intervention group will receive access to the smartphone application for 6 weeks post birth. Both Intervention and control groups will receive standardized institutional postnatal care services. Trial funding was gained from respective grant sponsors in May and November 2016.; Discussion: The Support for New Mums smartphone application could be a novel method for addressing the gap in provision of postpartum care services providing psychoeducation and improving maternal parental self-efficacy for Australian childbearing women.; Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12618001580268. (© 2019 John Wiley & Sons Ltd.)

Febrina, F., et al. (2022). "Efficacy of interventions to manage sexual dysfunction in women with cancer: A systematic review." Menopause 29(5): 609-626.
	Importance:Cancer and its treatment negatively affect female sexual health and function. The prevalence of female sexual dysfunction after cancer is between 33% and 43%. Numerous studies have addressed treatment options for sexual dysfunction in women with cancer, but it still remains a challenge to select the most efficacious option for patients. Objective(s):To compile and appraise recent evidence of any interventions for managing sexual dysfunction in female cancer survivors.Evidence Review:A literature search of the electronic databases MEDLINE, EMBASE, PsycINFO, and Cochrane Central Register of Controlled Trials (January 2011 to February 2021) was conducted using general search terms of "women", "cancer", "intervention", "sexual dysfunction". We included randomized controlled trials (RCTs) and uncontrolled before-after studies that evaluated the efficacy of intervention for female sexual dysfunction in women with history of cancer. Methodological quality of studies was assessed using Risk of Bias (RoB) 2.0 for RCTs and National Institutes of Health (NIH) assessment tools for uncontrolled before-after studies. Finding(s):Thirty-six studies were included for qualitative synthesis (14 RCTs (n = 1284), 17 uncontrolled trials (n = 589), and 5 cohort studies (n = 497). Only four studies were at low risk of bias. Topical interventions (vaginal gels or creams) were able to alleviate vaginal dryness and dyspareunia, with intravaginal dehydroepiandrosterone (DHEA) (6.5 mg) gel showing evidence of improved sexual function. Evidence for estriol-lactobacilli vaginal tablets was unreliable due to a small-scale study. Psychoeducational therapy (internet-based cognitive behavioral therapy [CBT]) studies typically were at high risk of bias, but all displayed significant improvements of sexual function. Both laser therapy (fractional CO2and erbium) and multimodal approach studies were at concerning risk of bias, although suggesting beneficial effects on sexual function. Conclusions and Relevance:The most reliable evidence for improvement was from a study of DHEA vaginal gel, but in general, gels or creams were useful in reducing dyspareunia. Pharmacological, psychoeducational, laser therapy, and multimodal approaches demonstrated potential in managing cancer-related sexual issues, but most were small in size (10-70 participants), with moderate to high risk of bias. Therefore, large-scale, double-blind, RCTs with long-period follow-up, and at low risk of bias are needed to show efficacy for these interventions.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Feduniw, S., et al. (2020). "Epidemiology, prevention and management of early postpartum hemorrhage - a systematic review." Ginekologia polska 91(1): 38-44.
	Early Postpartum Hemorrhage (EPH) is one of the leading causes of postpartum mortality. It is defined as blood loss of at least 500 mL after vaginal or 1000 mL following cesarean delivery within 24 hours postpartum. The following paper includes literature review aimed to estimate the incidence and predictors of early postpartum hemorrhage (EPH). Available prevention and treatment methods were also assessed. The inclusion criteria for the study were met by 52 studies. The exact frequency of EPH in different populations varies from 1.2% to 12.5%. Maternal, pregnancy-associated, laborcorrelated and sociodemographic risk factors seem to be important predictors of EPH. In these cases appropriate prophylaxis should be considered. However, EPH may occur without previous risk factors. The main reason for EPH is uterine atony which contributes to up to 80% of cases of postpartum hemorrhage (PPH). Other common reasons for PPH include genital tract injuries, placenta accreta or coagulopathies. Interestingly, the majority of uterotonics seem to have a similar effect. However, carbetocin seems to be the most effective in certain situations. Appropriate diagnosis of EPH is the most important issue. The treatment should be causative. The first-line treatment should include uterotonics. Surgical interventions, if required, should be performed without delay, although preoperative uterine tamponade should be considered due to its high effectiveness. Medical staff training in medical simulation centers is an important factor that improves the outcomes of EPH treatment. It provides adaptation to hospital protocols, team work improvement, self-confidence building, more accurate blood loss evaluation and reduced perception of stress. The implementation of systematic trainings provides better outcomes in the future.

Feferkorn, I., et al. (2023). "Estimation of follicular growth-widely used, seldom studied." Human fertility (Cambridge, England) 26(5): 1173-1178.
	We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient's age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1-4 days before trigger, does not affect pregnancy rates.

Fehm, T., et al. (2022). "Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities." Geburtshilfe und Frauenheilkunde 82(2): 181-205.
	Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.; Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of all the authors are listed in the long German-language version of the guideline report./Die Interessenkonflikte der Autoren sind im Leitlinienreport aufgelistet. (Thieme. All rights reserved.)

Fei, F., et al. (2021). "Effect of nalbuphine, dezocine or sufentanil combined with propofol in painless induced abortion." 中国计划生育学杂志 29(7): 1356‐1359.
	Objective: To compare the clinical effect of propofol combined with nalbuphine, dezocine and sufentanil for painless induced abortion. Methods: From January 2019 to June 2020, 156 early pregnant women who planned to undergo voluntary painless induced abortion in our hospital were selected and divided into 3 groups according to the random number table method, 52 cases in each group. Xin, propofol combined with nalbuphine in group B, and propofol combined with sufentanil in group C. The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), blood oxygen saturation (SpO2), anesthesia and adverse reactions were compared between the groups at different times of surgery. Results: Before administration and when the eyelash reaction disappeared, the SBP, DBP and SpO2 of group B were higher than those of group A and group C (P<0.05). The dosage of propofol (113.7±10.3mg) and recovery time (3.35±0.4min) in group B were less than those in group A (132.2±21.5mg, 7.1±1.3min) and group C (129.4±15.7mg, 5.8±0.9min) (P<0.05), the total incidence of adverse reactions in group B (19.2%) was lower than that in group A (57.7%) and group C (53.9%) (P<0.05). Conclusion: The anesthetic efficacy and safety of propofol combined with nalbuphine are better than those of propofol combined with dezocine or sufentanil.

Feiyi, Z., et al. (2021). "Acupuncture as an independent or adjuvant management to standard care for perimenopausal depression: a systematic review and meta-analysis."
	
Fei-yi, Z., et al. (2021). "Acupuncture for perimenopause insomnia: An overview of systematic reviews and meta-analyses."
	
Felder, L., et al. (2022). "How does colpocleisis for pelvic organ prolapse in older women affect quality of life, body image, and sexuality? A critical review of the literature." Women's Health 18.
	Colpocleisis is a surgical treatment for pelvic organ prolapse that results in vaginal obliteration. This review aims to systematically evaluate the quality of life, changes in body image, regret, and impact on sexual activity in women after colpocleisis. A review was conducted using the PubMed and Scopus databases with search criteria specifying pelvic organ prolapse, colpocleisis, quality of life, body image, regret, sexuality, and their synonyms. For the selection of the eligible articles, we used the PRISMA reporting system. A total of 1285 articles were found. After removing duplicates and applying the inclusion and exclusion criteria, 30 articles were reviewed in full length. Quality of life after colpocleisis was evaluated in 22 articles, and 20 authors used validated questionnaires. All concluded that quality of life improved after surgical treatment. Twenty-one articles studied regret after obliterative treatment for pelvic organ prolapse. Most of the patients reported no regret. Regret was often due to bowel and bladder symptoms. A few patients reported regret because of loss of coital function. Body image was highlighted in six studies. Three articles assessed body image using the modified Body Image scale. The body image scores demonstrated a significant improvement after surgery. Women tended to remain sexually active and some also regained sexual activities after surgery. Colpocleisis remains a viable option for pelvic organ prolapse, without compromising quality of life, body image, or sexuality, but diligent patient selection is needed. Particular concern should be given to bladder and bowel symptoms since these are the main reason for dissatisfaction after colpocleisis.Copyright © The Author(s) 2022.

Felip, E., et al. (2023). "Impact of chemotherapy and/or immunotherapy on neutralizing antibody response to SARS-CoV-2 mRNA-1237 vaccine in patients with solid tumors." Molecular Oncology 17(4): 686-694.
	Patients with solid tumors have been a risk group since the beginning of the SARS-CoV-2 pandemic due to more significant complications, hospitalizations or deaths. The immunosuppressive state of cancer treatments or the tumor itself could influence the development of post-vaccination antibodies. This study prospectively analyzed 89 patients under chemotherapy and/or immunotherapy, who received two doses of the mRNA-1237 vaccine, and were compared with a group of 26 non-cancer individuals. Information on adverse events and neutralizing antibodies against the ancestral strain of SARS-CoV-2 (WH1) have been analyzed. Local reactions accounted for 65%, while systemic reactions accounted for 46% of oncologic individuals/cancer patients. Regarding the response to vaccination, 6.7% of cancer patients developed low neutralizing antibody levels. Lower levels of neutralizing antibodies between cancer and non-cancer groups were significant in individuals without previous SARS-CoV-2 infection, but not in previously infected individuals. We also observed that patients receiving chemotherapy or chemoimmunotherapy have significantly lower levels of neutralizing antibodies than non-cancer individuals. In conclusion, our study confirms the importance of prioritizing cancer patients receiving anticancer treatment in SARS-CoV-2 vaccination programs.Copyright © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Feng, C., et al. (2021). "Application observation of mental health education combined with control of negative pressure suction pressure in high-risk early pregnancy patients with induced abortion." 当代护士·专科版 28(7): 108‐110.
	Objective: To study the clinical effect of combined control of negative pressure suction pressure with health education and psychological nursing in induced abortion in patients with high‐risk early pregnancy. Methods: A total of 148 patients with high‐risk early pregnancy who were treated in our hospital from June 2017 to January 2019 were selected as the research objects, and they were randomly divided into an observation group and a control group, 74 cases in each group. Both groups underwent painless artificial abortion. The surgical suction pressure was 100‐400 mmHg, and the suction time was less than or equal to 75 s. The control group received routine nursing; the observation group received routine nursing and health education and psychological nursing intervention. The intraoperative conditions, anxiety and postoperative complications of the two groups were observed and recorded. Results: After nursing intervention, the self‐rating anxiety scale (SAS) score of the observation group was significantly lower than that of the control group, and the difference was statistically significant (P<0.001). The intraoperative blood loss in the observation group was less than that in the control group, and the difference was statistically significant (P<0.001). The total incidence of postoperative complications in the observation group was lower than that in the control group, and the difference was statistically significant (P<0.05). Conclusion: Carrying out health education and psychological nursing for high‐risk early pregnancy patients in the process of induced abortion, while controlling the suction pressure and suction time of negative pressure can relieve the patient's negative psychological mood, improve the surgical effect, and reduce the occurrence of postoperative complications, which is worthy of promotion. application.

Feng, C. and L. Yingran (2023). "Moxifloxacin monotherapy for treatment of uncomplicated pelvic inflammatory disease: A meta-analysis of randomized controlled trials."
	
Feng, H., et al. (2022). "The effectiveness and safety of Chinese herbal medicine in infertile women with luteal phase deficiency: a systematic review and meta-analysis." Annals of Palliative Medicine 11(7): 2492-2502.
	BACKGROUND: Chinese herbal medicine (CHM) has been reported to treat infertile women with luteal phase deficiency (LPD) in some clinical studies, however, the efficacy and safety of CHM for LPD are still under controversy. Here, we aim to evaluate the efficacy and safety of CHM using meta-analysis, and further compare it with conventional Western therapies (CWT) to elucidate the improvement in progestin and clinical pregnancy rates. METHOD(S): Eight randomized controlled trials (RCTs) involving 465 women were included in our systematic review; these RCTs compared CHM with CWT in treating LPD in infertile women. The methodological quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment criteria. The data were analyzed by Review Manager 5.3 software. We estimated the risk ratio (RR) for dichotomous data and calculated the mean difference for continuous data. RESULT(S): In contrast to CWT, CHM was superior in improving clinical pregnancy rates (RR 0.19; 95% CI: 0.11-0.27; P<0.001), increasing progesterone levels in the luteal phase [mean difference (MD) 2.28; 95% CI: 1.91-2.64; P<0.001] and luteal phase estrogen (MD 9.88; 95% CI: 4.53-15.24; P=0.0003), reducing traditional Chinese medicine (TCM) syndrome scores (MD -3.06; 95% CI: -3.95 to -2.17; P<0.001), and the incidence of adverse reactions (RR 0.12; 95% CI: 0.02-0.70; P=0.02). CONCLUSION(S): Evidence from eight small studies suggested that CHM has a therapeutic effect on infertile women with luteal insufficiency. We indicated that CHM may improve the level of progesterone and estradiol in the luteal phase, and the clinical pregnancy rate, with few side effects based on the current studies. However, given the relatively small number of included studies, further studies about the higher quality of study designs, larger population and the underlying mechanism are required to elucidate the role of CHM in LPD treatment.

Feng, J., et al. (2021). "The Efficacy of Complementary and Alternative Medicine in the Treatment of Female Infertility." Evidence-based complementary and alternative medicine : eCAM 2021: 6634309.
	Female infertility is a state of fertility disorder caused by multiple reasons. The incidence of infertility for females has significantly increased due to various factors such as social pressure, late marriage, and late childbirth, and its harm includes heavy economic burden, psychological shadow, and even marriage failure. Conventional solutions, such as hormone therapy, in vitro fertilization (IVF), and embryo transfer, have the limitations of unsatisfied obstetric outcomes and serious adverse events. Currently, complementary and alternative medicine (CAM), as a new treatment for infertility, is gradually challenging the dominant position of traditional therapies in the treatment of infertility. CAM claims that it can adjust and harmonize the state of the female body from a holistic approach to achieve a better therapeutic effect and has been increasingly used by infertile women. Meanwhile, some controversial issues also appeared; that is, some randomized controlled trials (RCTs) confirmed that CAM had no obvious effect on infertility, and the mechanism of its effect could not reach a consensus. To clarify CAM effectiveness, safety, and mechanism, this paper systematically reviewed the literature about its treatment of female infertility collected from PubMed and CNKI databases and mainly introduced acupuncture, moxibustion, and oral Chinese herbal medicine. In addition, we also briefly summarized psychological intervention, biosimilar electrical stimulation, homeopathy, hyperbaric oxygen therapy, etc.

Feng, J., et al. (2020). "Efficacy of clomifene citrate combined Bushen Culuan Decoction for the treatment of infertility caused by polycystic ovary syndrome: A protocol of systematic review." Medicine 99(27): e20969.
	Background: The aim of this study is to assess the efficacy and safety of clomifene citrate combined Bushen Culuan Decoction (CCBCD) in treating infertility caused by polycystic ovary syndrome (PCOS).; Methods: We will carry out this study to identify eligible randomized controlled trials (RCTs) in Cochrane Library, PUBMED, EMBASE, Web of Science, CINAHL, and China National Knowledge Infrastructure from inception to the present. There are no limitations to the language and publication time. We will perform study selection, data extraction, and study quality assessment. If possible, a meta-analysis will be developed to judge the comparative efficacy and safety of CCBCD with other treatments.; Results: The results of this study will summarize current high quality RCTs to provide direct evidence of CCBCD in treating infertility in patients with PCOS.; Conclusion: This study may provide evidence to determine whether CCBCD is effective and safe or not for the treatment of infertility caused by PCOS.; Study Registration: INPLASY202050090.

Feng, J., et al. (2021). "Application of mobile APP in continuation intervention of women's post-abortion care program." Modern practical medicine / 现代实用医学 33(12): 1639‐1641.
	Objective: To explore the application effect of mobile APP in the continuation intervention of women's post‐abortion care (PAC) project. Methods: A total of 644 women who were required to undergo induced abortion were collected as the research objects, and they were divided into groups according to the admission numbers of the patients. The odd number was included in the observation group, and the double number was included in the control group. The control group was given conventional PAC, and the observation group was treated with mobile APP for PAC intervention. The application of this intervention in women with miscarriage. Results: The repeated abortion rates in the observation group within 1 year and within half a year were lower than those in the control group (all P<0.05); the negative emotion scores in the observation group after the intervention were lower than those in the control group (all P<0.05); the observation group was self‐management after the intervention The scores of behavior, self‐management environment and self‐management cognition were higher than those of the control group (all P<0.05); the non‐contraception rate, emergency contraceptives, rhythm contraception and other proportions in the observation group after intervention were lower than those in the control group, and the uterine The proportions of IUDs, oral contraceptives, and perfect condom use were higher than those in the control group (all P<0.05); postoperative bleeding time and menstrual bleeding volume in the observation group were lower than those in the control group, and menstrual recovery was better than that in the control group, but The recovery rate of sexual life was lower than that of the control group (all P<0.05). Conclusion: Mobile APP can improve patients' emotional state, improve self‐management ability, and promote the implementation of contraceptive measures in post‐abortion women's PAC project continuation intervention.

Feng, L. (2021). "bservation of curative effect of motherwort combined with progesterone + Premarin in regulating oligomenorrhea after induced abortion." Modern diagnosis and treatment / 现代诊断与治疗 32(21): 3376‐3378.
	Objective: To explore the therapeutic effect and safety of motherwort combined with progesterone + Premarin in patients with oligomenorrhea after induced abortion. Methods: A total of 168 patients with hypomenorrhea after induced abortion who were treated in our hospital from January 2018 to January 2020 were selected and randomly divided into the observation group and the control group with 84 cases in each group. The control group was treated with progesterone + Premarin, the observation group was treated with motherwort on the basis of the control group, the overall curative effect of the two groups of patients after treatment was compared, and the sex hormone indexes (including estradiol, progesterone), uterine Changes in endometrial thickness and incidence of adverse reactions during treatment. Results: After treatment, the overall treatment effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). Conclusion: Motherwort combined with progesterone + Premarin in patients with oligomenorrhea after induced abortion can improve the overall treatment efficiency, promote sex hormone endocrine and endometrial repair, and has good safety.

Feng, L., et al. (2022). "The effect of flexible low-dose GnRH antagonist on pregnancy outcome in the fresh embryo transfer cycle of IVF-ET: a randomized controlled trial." Reproductive biology and endocrinology : RB&E 20(1): 55.
	Objective: To explore the practicality and effectiveness of a flexible low‐dose protocol in the fresh embryo transfer cycle: reducing the total amount of antagonist by increasing the interval between administrations of Cetrotide. Methods: A total of 211 patients with normal ovarian reserve who accepted GnRH‐ant protocol for IVF‐ET were selected, and they were randomized to the flexible low‐dose antagonist group (test group, n = 101) or the conventional dose antagonist group (control group, n = 110). The initial dose of Cetrotide in the test group was 0.25 mg every other day, and then the dose was adjusted to 0.25 mg every day based on the subsequent luteinizing hormone (LH) levels. The dosage of Cetrotide in the control group was 0.25 mg per day. The primary outcome was the clinical pregnancy rate. Secondary outcomes included the incidence of premature LH rise, total dosage of Cetrotide, number of oocytes retrieved, number of fertilized oocytes, number of high‐quality embryos, biochemical pregnancy rate and ongoing pregnancy rate. Results: There was no significant difference in the general condition of the two groups. There was no significant difference in the clinical pregnancy rate (51.49% vs. 48.18%, p = 0.632) or the incidence of premature LH rise (18.81% vs. 15.45%, p = 0.584) between the two groups. However, the amount of Cetrotide used in the test group was significantly lower than that in the conventional dose antagonist group (1.13 ± 0.41 vs. 1.61 ± 0.59 mg, p < 0.001). Conclusion: The flexible low‐dose antagonist protocol and the conventional dose antagonist protocol were equally effective in people with a normal ovarian reserve in the fresh embryo transfer cycle of IVF‐ET.

Feng, Q. (2021). "Clinical observation of estrogen-progestin combination in the treatment of incomplete induced abortion." 医药前沿 11(16): 42‐43.
	Objective: To observe the clinical effect of estrogen‐progestin combination in the treatment of incomplete induced abortion. Methods: Select 100 patients with incomplete induced abortion who were treated in our hospital from January 2019 to January 2020 as the research objects, after numbering, they were divided into the study group (odd number) and the control group (even number), each Group of 50 cases. The control group was treated with conventional antibiotics, while the study group was treated with estrogen‐progestin combination. After 2 weeks of treatment, the bleeding frequency and average recovery time during the treatment were counted. Results: The number of bleeding in the study group within 2 weeks was less than that in the control group, and the healing time was shorter than that in the control group, and the difference was statistically significant (P<0.05). Conclusion: Combined estrogen‐progestin therapy in the treatment of incomplete induced abortion can effectively relieve the related symptoms of patients and shorten the treatment time. It has a positive effect on the recovery of patients and is worthy of clinical application.

Feng, W., et al. (2021). "Effect of Oral versus Vaginal Administration of Estradiol and Dydrogesterone on the Proliferative and Secretory Transformation of Endometrium in Patients with Premature Ovarian Failure and Preparing for Assisted Reproductive Technology." Drug design, development and therapy 15: 1521-1529.
	PURPOSE: This study aimed to assess the efficacy of vaginally versus orally administered estradiol (E2) and dydrogesterone (DG) on the proliferative and secretory transformation of endometrium in patients with premature ovarian failure (POF) and preparing for assisted reproductive technology. METHODS: Twenty patients with POF who were awaiting oocyte donation were included in the study; they were randomly assigned to two groups to receive E2 and DG either orally or vaginally. Treatment efficacy was compared between the two groups regarding blood E2 concentrations, endometrial thickness, histology using hematoxylin and eosin staining, immunohistochemical analysis of ER expression, and PR and pinopodes morphology using scanning electron microscopy. RESULTS: E2 concentrations differed significantly between oral and vaginal E2 and DG administration for 14 days (82.3 vs 1015.6 pg/mL; P < 0.001) and 21 days (85.0 vs 809.8 pg/mL; P < 0.001). Endometrial thickening was more pronounced in the vaginal treatment group, and also ER staining was stronger on days 14 and 21 in the vaginal treatment group. PR staining in the endometrium appeared more intense in the oral treatment group, which was, however, not significant. The abundance of developing pinopodes was higher in the vaginal treatment group (P = 0.04). CONCLUSION: Vaginal administration of E2 and DG is more effective than oral administration regarding proliferative and secretory transformation of the endometrium in POF patients and preparing for assisted reproductive technology.

Feng, Y., et al. (2019). "Comparison of PARPis with Angiogenesis Inhibitors and Chemotherapy for Maintenance in Ovarian Cancer: A Network Meta-Analysis." Advances in Therapy 36(12): 3368-3380.
	Introduction: Seventy-five percent of ovarian cancer would relapse within 18-28 months after platinum-base chemotherapy. Evidence suggests that maintenance chemotherapy is effective in prolonging remission. Recent target therapies such as poly(ADP-ribose) polymerase inhibitors (PARPis) and angiogenesis inhibitors (AIs) are known to ease burden and recurrence of ovarian cancer. There is limited data for head-to-head comparison of PARPis, AIs, and chemotherapeutic agents (CTAs) as maintenance treatment. This network meta-analysis thus assessed the effectiveness and toxicity of these three maintenance therapies in patients with ovarian cancer.; Methods: We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials assessing efficacy and safety of maintenance therapy in patients with ovarian cancer. Primary outcome was progression-free survival (PFS) as assessed by blinded review; safety and tolerability were secondary outcomes. A network meta-analysis to compare three drug classes was performed using statistical software R.; Results: We included 24 trials (11,366 patients) assessing efficacy and safety of PARPis (n = 4), AIs (n = 12), and CTAs (n = 8). PARPis [hazard ratio (HR) 0.64; 95% credible intervals (CrI) 0.55-0.73] and AIs (HR 0.87; 95% CrI 0.81-0.93) showed significant improvement in PFS compared to placebo but not CTA (HR 1.00; 95% CrI 0.86-1.15). PARPis showed significant improvement in PFS compared to AIs (HR 0.73; 95% CrI 0.63-0.86) and CTA (HR 0.64; 95% CrI 0.52-0.78). Adverse events (AEs) leading to treatment discontinuation and dose reduction were lower in PARPis [incidence rate ratio (IRR) 0.60; CrI 0.31-1.18 and IRR 0.73, 95% CrI 0.50-1.06, respectively] compared to AIs, but the differences were not significant.; Conclusion: PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of implications caused by AEs when compared to AIs. This network meta-analysis provides valuable evidence and significant insights into treatment of ovarian cancer.

Feng, Y., et al. (2019). "The security of radical trachelectomy in the treatment of IA-IIA cervical carcinoma requires further evaluation: updated meta-analysis and trial sequential analysis." Archives of Gynecology and Obstetrics 299(6): 1525-1536.
	Purpose: The aim of this study was to assess the security of radical trachelectomy (RT) in the treatment of IA-IIA cervical carcinoma and conducted a new survey based upon the results of previous researches.; Methods: The PMC, PubMed, Web of Science, Cochrane and EMBASE databases were retrieved to collect prospective clinical controlled trials (CCTs) published from 1984 to 2018. The oncologic outcomes were evaluated by meta-analysis, trial sequence analysis (TSA) and statistical analysis.; Results: Five prospective CCTs were collected in this study. The recurrence rate and mortality of RT was similar to that of radical hysterectomy (RH), which was consistent with the oncologic outcomes of meta-analysis and TSA. Patients with tumors 2-4 cm in diameter were more likely to receive RH, which may be a potential factor in the higher rate of adjuvant chemotherapy in the this group, and RH was significantly associated with the risk of intraoperative blood transfusion. It is notable that considerable negative margin was achieved by radical abdominal trachelectomy (RAT), and the clinical effect of RAT was slightly better than that of radical vaginal trachelectomy (RVT). However, the TSA results showed that the cumulative cases were not up to the required sample size to obtain the true negative or positive results.; Conclusions: It is safe and effective for early-stage patients with cervical cancer whose lesions are less than 2 cm to receive RVT. For those patients with lesions 2-4 cm who desire fertility preservation and without any evidence of infertility, RAT can be a feasible alternative to RH under fully informed consent. However, more CCTs with larger sample size are still required for further validation.

Feng, Y. Y., et al. (2021). "Psychological or educational eHealth interventions on depression, anxiety or stress following preterm birth: a systematic review." Journal of Reproductive and Infant Psychology 39(2): 140-152.
	Objective: To determine the efficacy and characteristics of psychological or educational eHealth interventions on reducing symptoms of mental illness in parents of preterm or low birthweight infants. Background(s): Many parents suffer psychological disorders after preterm birth. Computer or mobile application-based interventions are a promising alternative. Method(s): We searched seven electronic databases up to January 2020 and included randomised and quasi-randomised controlled trials assessing psychological or educational eHealth interventions in parents of infants born very preterm <32 weeks or with very low birthweight <1500g (primary question), or preterm <37 weeks or with low birthweight <2500g (secondary question). Primary outcomes were measures of depression, anxiety, acute stress disorder or post-traumatic stress disorder. Secondary outcomes included other indicators of mental health, quality of life and intervention characteristics. We had planned random-effects meta-analysis in our protocol (CRD42018105731). Result(s): Of 9768 records, no study reported our primary outcomes. Three studies showed potential benefits for parental self-efficacy, discharge preparedness, parental satisfaction and family satisfaction with the neonatal intensive care unit. Conclusion(s): We found scarce evidence on the efficacy of psychological or educational eHealth interventions on reducing mental illness in parents of preterm or low birthweight infants, highlighting the need for more research.Copyright © 2020 Society for Reproductive and Infant Psychology.

Fengping, S., et al. (2022). "Meta analysis efficacy of the combination metformin and progestin for women with early endometrial cancer or endometrial hyperplasia."
	
Fenocchi, L., et al. (2023). "Long-term effects and costs of pelvic floor muscle training for prolapse: trial follow-up record-linkage study." International Urogynecology Journal 34(1): 239-246.
	Introduction and Hypothesis: Pelvic organ prolapse affects around 40% of women aged over 50 years. A multicentre parallel group randomised trial (the Pelvic Organ Prolapse PhysiotherapY (POPPY) trial) demonstrated that pelvic floor muscle training (PFMT) was effective in reducing prolapse symptoms compared with no treatment. However, insight into the long-term impact of PFMT on health outcomes and health-service utilisation is scarce.; Methods: This study utilised linkage of Scottish administrative health records to follow-up POPPY trial participants resident in Scotland over 11 years. Mixed effects logistic regression determined the likelihood of receiving further prolapse treatment for those in the PFMT and control groups. Analyses were adjusted for age group, prolapse stage, baseline symptom severity and attitude towards surgery. A cost assessment estimated longitudinal costs to the UK National Health Service (in Scotland) of accessing further prolapse treatment for each trial group.; Results: Two hundred and ninety-three women, aged 25 to 79 years, were followed up. One hundred and forty-one women (48.1%) had received further prolapse treatment: 65 (of 149; 43.6%) in the PFMT group compared with 76 (of 144; 52.8%) in the control group. PFMT was associated with a reduction in the odds of any prolapse treatment during follow-up (AOR 0.61; 95% CI 0.37 to 0.99). Total cost of secondary care was £154,544 (GBP) in the PFMT group and £172,549 (GBP) in the control group.; Conclusions: Although PFMT did not lead to significant differences in total costs for further prolapse treatment over a post-intervention period of more than 10 years, it reduced the overall long-term risk of requiring hospital-based treatment for pelvic floor disorders. (© 2022. The Author(s).)

Fernanda Sayuri, F., et al. (2021). "Effect of pelvic floor muscle training on urinary incontinence symptoms in women who practice high-impact sports: a systematic review." PROSPERO International prospective register of systematic reviews.
	
Fernandez, g., et al. (2023). "Comparison of progesterone levels according to the type of vaginal micronized progesterone used for luteal phase support in artificial-cycles for endometrial preparation in embryo transfer."  38: i451.
	Study question: Are there differences in the ongoing pregnancy rate (OPR) using Cyclogest® versus Progeffik® at a dose of 800 mg daily as luteal phase support? Summary answer: The administration of Cyclogest® as luteal phase support shows higher ongoing pregnancy rates (OPR) in a cycle of hormone replacement therapy (HRT) with own oocytes What is known already: The importance of serum progesterone levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established; some studies have shown that optimizing serum progesterone levels on the day before, leads to an improvement in live birth rates (LBR). However, to date, no study has examined which vaginal preparation reports better serum progesterone levels and its impact on OPR. Study design, size, duration: This prospective randomized clinical trial was performed between September 2019 and June 2022 and enrolled 490 patients scheduled for cryopreserved ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal progesterone. They were divided into two groups, those who used Progeffik® and others with Cyclogest® total dose of 800mg. SPLs were measured the day before (P+4), the day of the transfer (P+5) and the day of BHCG (P+19) and compared the OPR. Participants/materials, setting, methods: Patients between 18‐40 years of age with BMI <30 and triple‐layer endometrium > 7,5mm underwent transfer of one blastocysts with own oocytes. The study was carried out in the assisted human reproduction unit of the Virgen de Valme University Hospital (Seville). Ethical approval was granted and formed consent was obtained. The primary endpoint is to assess which vaginal progesterone preparation gives better ongoing pregnancy rates. Main results and the role of chance: The 484 patients were randomized (1:1) into two groups. Progeffik was administered to 149 patient and Cuyclogest to 335 patient. The characteristics of the patients were comparable between groups with similar causes of fertility and type of IVF. Regarding the results of serum progesterone levels measured according to the type of micronized vaginal progesterone used to support the luteal phase, we obtained for day P+4 (13,69 for Progeffik® vs 15.89 for Cyclogest® ), while for day P+5 (11.95 vs 17.69) and on day P+19 (13.69 vs 15.41), the results obtained after the administration of Cyclogest® being significantly higher with a p‐value of 0,01. When assessing the ongoing pregnancy rate, they were also significantly higher with the administration of Cyclogest® versus Progeffik® (59.7% vs 48.3%) with a p value of 0,024. Limitations, reasons for caution: The newborm rate needs to be validated as it has not exceeded 9 months since the study. Wider implications of the findings: This study demonstrates the statistically significant superiority of Cyclogest‐type vaginal micronized progesterone administration over its competitor Progeffik used for luteal phase support, being a more convenient way of administration for women since it's simplicity.

Fernandez, H., et al. (2023). "Update on the management of endometriosis-associated pain in France." Journal of Gynecology Obstetrics and Human Reproduction 52(9): 102664.
	The French National College of Obstetricians and Gynecologists (CNGOF) published guidelines for managing endometriosis-associated pain in 2018. Given the development of new pharmacological therapies and a review that was published in 2021, most national and international guidelines now suggest a new therapeutic approach. In addition, a novel validated screening method based on patient questionnaires and analysis of 109-miRNA saliva signatures, which combines biomarkers and artificial intelligence, opens up new avenues for overcoming diagnostic challenges in patients with pelvic pain and for avoiding laparoscopic surgery when sonography and MRI are not conclusive. Dienogest (DNG) 2 mg has been a reimbursable healthcare expense in France since 2020, and, according to recent studies, it is at least as effective as combined hormonal contraception (CHC) and can be used as an alternative to CHC for first-line treatment of endometriosis-associated pain. Since 2018, the literature concerning the use of DNG has grown considerably, and the French guidelines should be modified accordingly. The levonorgestrel intrauterine system (LNG IUS) and other available progestins per os, including DNG, or the subcutaneous implant, can be offered as first-line therapy, gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (ABT) as second-line therapy. Oral GnRH antagonists are promising new medical treatments for women with endometriosis-associated pain. They competitively bind to GnRH receptors in the anterior pituitary, preventing native GnRH from binding to GnRH receptors and from stimulating the secretion of luteinizing hormone and follicle-stimulating hormone. Consequently, estradiol and progesterone production is reduced. Oral GnRH antagonists will soon be on the market in France. Given their mode of action, their efficacy is comparable to that of GnRH agonists, with the advantage of oral administration and rapid action with no flare-up effect. Combination therapy with ABT is likely to allow long-term treatment with minimal impact on bone mass. GnRH antagonists with ABT may thus be offered as second-line treatment as an alternative to GnRH agonists with ABT. This article presents an update on the management of endometriosis-associated pain in women who do not have an immediate desire for pregnancy.; Competing Interests: Conflict of Interest H Fernandez: Gedeon Richter, Theramex A Agostini: Gedeon Richter, Theramex H Baffet: pas de liens d'intérêt N Chabbert Buffet: Bayer, Besins, Exeltis, Gedeon Richter, Organon, Theramex P Descamps: Gedeon Richter, Theramex JP Estrade: Gedeon Richter G Giraudet: Gedeon Richter, Theramex C. Hocké: Gedeon Richter, IBSA Pharma, Exeltis B Salle: pas de liens d'intérêt F Trémollieres: pas de liens d'intérêt C Chapron: Gedeon Richter, Theramex (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Fernandez, S., et al. (2023). "Impact of Enhanced Recovery After Surgery (ERAS) program in gynecologic oncology and patient satisfaction." Journal of Gynecology Obstetrics and Human Reproduction 52(2): 102528.
	Objective: The primary objective of this study was to compare lengths of stay since ERAS program implementation. We also evaluated ERAS protocol compliance, compared the outpatient rate, the complication rate and the readmission rate within 30 days after surgery and performed a satisfaction study.; Methods: This is a monocentric comparative study with a historical control group, performed in the gynecological surgery department of the University Hospital of Saint-Etienne. We compared a group of patients who underwent surgery in 2016, before the implementation of ERAS program, with a group of patients who underwent surgery from July 2021 to July 2022, for whom ERAS program was applied.; Results: 187 patients were included in this study, including 84 patients in the historical group before ERAS and 103 in the group with ERAS. Considering all approaches, the average length of stay decreased by 2 days (p<0.0001). Considering minimally invasive surgery, the outpatient rate increased from 5% to 50% (p<0.0001) and complication rate decreased from 23 to 11% (p = 0,04). The readmissions rate was similar. Satisfaction score for patients managed with ERAS program was 8.9/10.; Conclusion: The implementation of ERAS program in gynecological oncology surgery allowed a reduction in length of stay, with a high outpatient rate, decreasing complications in case of minimally invasive surgery, without increasing the readmission rate, and was associated with good patient satisfaction. (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Fernández-Cuadros, M. E., et al. (2020). "[Effectiveness of multimodal rehabilitation (biofeedback plus capacitive-resistive radiofrequency) on chronic pelvic pain and dyspareunia: prospective study and literature review]." Rehabilitacion.
	OBJECTIVE: To determine whether a multimodal rehabilitation protocol (Biofeedback [BFB] plus capacitive-resistive [INDIBA®] radiofrequency [RF]) reduces pain and increases muscular strength in patients with chronic pelvic pain (CPP) and dyspareunia. MATERIAL AND METHODS: We performed a prospective, quasi-experimental, before-after study in 37 patients with CPP and/or dyspareunia referred to the Rehabilitation Department of Hospital Universitario Santa Cristina (January 2016 to December 2018). The protocol consisted of 8 sessions of pelvic floor exercises assisted by manometric BFB (15min of tonic/phasic exercises each) supervised by a physiotherapist, followed by suprapubic and perineovaginal bipolar RF [capacitive(5 min)/resistive(10 min)]. The variables evaluated were pain (VAS 0-10) and strength (mmHg) of the pelvic floor musculature and the start/end of the treatment. RESULTS: The mean age was 41.5±12.65 years. The prevalence was higher among women aged 21-40 years (n=20, 54%) and those aged 41-60 years (n=12; 32.4%). Dyspareunia was present in 34 patients (91.8%), and non-specific CPP in 3 (8.2%). The protocol improved pain (from 7.27±1.34 to 3.75±2.21 points), maximal muscular strength (from 25.56±15.9mmHg to 35.35±20.4mmHg) and mean muscular strength (from 4.86±3.53mmHg to 7.18±4.46mmHg) respectively (p<0.0001). CONCLUSION: CPP and dyspareunia are a diagnostic challenge that requires multidisciplinary management. Treatment should be started early and should consist of distinct therapeutic modalities. The protocol of multimodal rehabilitation including BFB and capacitive-resistive RF reduces pain and improves strength in patients with CPP and dyspareunia.

Fernández-Férez, A., et al. (2021). "Nursing Interventions to Facilitate the Grieving Process after Perinatal Death: A Systematic Review." International Journal of Environmental Research and Public Health 18(11).
	Perinatal death is the death of a baby that occurs between the 22nd week of pregnancy (or when the baby weighs more than 500 g) and 7 days after birth. After perinatal death, parents experience the process of perinatal grief. Midwives and nurses can develop interventions to improve the perinatal grief process. The aim of this review was to determine the efficacy of nursing interventions to facilitate the process of grief as a result of perinatal death. A systematic review of the literature was carried out. Studies that met the selection criteria underwent a quality assessment using the Joanna Briggs Institute critical appraisal tool. Four articles were selected out of the 640 found. Two are quasi-experimental studies, and two are randomized controlled clinical studies. The interventions that were analyzed positively improve psychological self-concept and role functions, as well as mutual commitment, depression, post-traumatic stress and symptoms of grief. These interventions are effective if they are carried out both before perinatal loss and after it has occurred. The support of health professionals for affected parents, their participation in the loss, expressing feelings and emotions, using distraction methods, group sessions, social support, physical activity, and family education are some of the effective interventions.

Fernandez-Montoli, M.-E., et al. (2021). "Fertility-Sparing Treatment for Atypical Endometrial Hyperplasia and Endometrial Cancer: A Cochrane Systematic Review Protocol." Advances in Therapy 38(5): 2717-2731.
	Introduction: Endometrial cancer is the fifth most common cancer in women and atypical endometrial hyperplasia is a precancerous lesion. Obesity is an important risk factor for endometrioid endometrial adenocarcinoma and endometrial hyperplasia. Progesterone is recommended as first-line treatment in endometrial cancer or atypical endometrial hyperplasia in women who wish to preserve fertility, but optimal treatment schedules have not been defined. Metformin or bariatric surgery may also be useful in these women. The effectiveness and safety of fertility-preserving treatments being used for women with atypical endometrial hyperplasia and stage IA grade 1 endometrial cancer is unclear. Therefore, the systematic review aims to determine this point.; Methods: We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trial registers, conference proceedings, abstracts, cooperative trial groups and reference lists. We will include randomised controlled trials (RCTs) that compare fertility-preserving therapy including orally administered progesterone versus a levonorgestrel-releasing intrauterine system (IUS), metformin, other pharmacological interventions or bariatric surgery, and any of these interventions with womb-removing surgery. Quasi-randomised trials, non-randomised trials and cohort studies will be included. Two review authors will independently assess study eligibility and risk of bias and extract data. The primary outcomes are complete pathologic response and live birth rate. Secondary outcomes include overall survival, progression-free survival, pregnancy rate, need for hysterectomy, adverse events, psychological symptoms and quality of life.; Planned Outcomes: This review aims to clarify the effectiveness and risks of fertility-preserving treatments, including complete pathologic response rate, live birth rates, need for surgical treatment, adverse events, psychological symptoms and quality of life. The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy.; Results: The results may help to determine the optimal fertility-sparing treatment in endometrial cancer and atypical endometrial hyperplasia.; Systematic Review Registration: Prospero 2019 number CRD42019145991.

Fernandez-Vaz, C. and J. D. Gonzalez-Sanz (2022). "Cortisol, Maternal Stress, and Breastfeeding Rate at Hospital Discharge: A Systematic Review." Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine.
	Introduction: Breastfeeding is considered the best way to provide essential and necessary nutrients to the newborn, intervening in its growth and development. However, early abandonment of this method is quite common, due to various factors such as stress. Objectives: To determine whether the level of postpartum cortisol can serve as an indicator of maternal stress and whether there is a relationship between the level of cortisol and the rate of exclusive breastfeeding (EBF) at hospital discharge. Methodology: Systematic review of the literature under the PRISMA guidelines. PubMed, Web of Science, CINAHL, and Scopus databases were used. Original articles published from 2017 to 2022 in English, French, Portuguese, and Spanish were included. All study designs were eligible. Of the 3,712 records initially identified, 15 studies were included in this review. Results: Elevated cortisol levels, due to immediate postpartum stressors, have direct effects on the performance of the essential hormones in breast milk production. The EBF rates are negatively influenced by perceived maternal stress. Conclusion: Cortisol levels may be a good indicator of the level of stress to which the mother is subjected during the immediate postpartum period.

Fernlund, A., et al. (2021). "Psychological impact of early miscarriage and client satisfaction with treatment: comparison between expectant management and misoprostol treatment in a randomized controlled trial." Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 58(5): 757-765.
	OBJECTIVES: To compare the short- and long-term emotional distress (grief, anxiety and depressive symptoms) after early miscarriage and satisfaction with treatment between women randomized to expectant management vs vaginal misoprostol treatment. METHODS: This was a preplanned analysis of data collected during a randomized controlled trial comparing expectant management with misoprostol treatment in women with early anembryonic or embryonic miscarriage and vaginal bleeding. If the miscarriage was not complete on day 31 after inclusion, surgical evacuation was recommended. The main outcomes were levels of anxiety and grief, depressive symptoms and client satisfaction with the treatment, which were assessed using the following validated psychometric self-assessment instruments: Spielberger State-Trait Anxiety Inventory (STAI, Form Y), Perinatal Grief Scale (PGS), Montgomery-Åsberg Depression Rating Scale (MADRS-S; self-reported version) and Client Satisfaction Questionnaire (CSQ-8). All women were assessed at four timepoints: on the day of randomization, on the day when the miscarriage was judged to be complete, and at 3 months and 14 months after complete miscarriage. The psychometric and client satisfaction scores were compared between the misoprostol group and the expectant-management group at each assessment. Analysis was performed by the intention-to-treat principle. RESULTS: Ninety women were randomized to expectant management and 94 to misoprostol treatment. The psychometric and client satisfaction scores were similar in the two treatment groups at all assessment timepoints. At inclusion, 41% (35/86) of the women managed expectantly and 37% (34/92) of those treated with misoprostol had a STAI-state score of > 46 ('high level of anxiety'), and 9% (8/86) and 10% (9/91), respectively, had symptoms of moderate or severe depression (MADRS-S score ≥ 20). In both treatment groups, symptom scores for anxiety and depression were significantly higher at inclusion than after treatment and remained low until 14 months after complete miscarriage. Grief reactions were mild in both groups, with a median PGS score of 40.0 at 3 months and 37.0 at 14 months after complete miscarriage in both treatment groups. Four women treated with misoprostol and two women managed expectantly had a PGS score of > 90 (indicating deep grief) 3 months after complete miscarriage, while one woman managed expectantly had a PGS score of > 90 14 months after complete miscarriage. Women in both treatment groups were satisfied with their management, as indicated by a median CSQ-8 score of > 25 at each assessment. More than 85% of participants in each of the two groups reported that they would recommend the treatment they received to a friend. CONCLUSIONS: The psychological response to and recovery after early miscarriage did not differ between women treated with misoprostol and those managed expectantly. Satisfaction with treatment was high in both treatment groups. Our findings support patient involvement when deciding on the management of early miscarriage. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ferradas-Galloso, M., et al. (2022). "Therapeutic Exercise Combined or not with Pelvic Floor Muscle Training for Urinary Incontinence." Archivos Espanoles de Urologia 75(6): 494-506.
	INTRODUCTION: The most used physiotherapy treatment is the pelvic floor muscle training. Other factors are involved in the control of urination, such as the management of abdominal pressure and the activity of the muscles and fascia of the lumbopelvic region and this could be trained through generalized therapeutic exercise, which is defined as an intervention aimed at restoring musculoskeletal, cardiopulmonary and neurological function. The objective of this review is to evaluate the effects of therapeutic exercise, combined or not with analytical training of the pelvic floor muscles, on urinary incontinence in women over 18 years of age, by reviewing the scientific literature. OBJECTIVE(S): To assess the effects of therapy exercise other than or combined with pelvic floor muscle training on urinary incontinence in women over 18 years. MATERIAL AND METHODS: An article research was done between 11th January and 7th February, 2021 on the following databases: Pubmed, Medline, Cinahl, Web Of Science, Sport Discus and PEDro using the search terms "Urinary Incontinence" and "Exercise Therapy". RESULT(S): An average of 245 results were obtained, of which 10 were selected after applying the eligibility criteria. The interventions of the analyzed articles are divided into two groups. First, a group where muscles of the abdominal-pelvic-perineal region are worked (hypopressives, yoga and strength of the abdominal muscles, resisted hip rotation...). Secondly, another group where muscles in general are worked (weight training, flexibility, balance and toning and cardiovascular training). CONCLUSION(S): Urinary incontinence treated with therapy exercise other than the pelvic floor muscles training, or combined with it, suggest improvements in symptoms.

Ferrando, C. A. and M. F. R. Paraiso (2021). "A prospective randomized trial comparing Restorelle® Y mesh and flat mesh for laparoscopic and robotic-assisted laparoscopic sacrocolpopexy: 24-month outcomes." International Urogynecology Journal 32(6): 1565-1570.
	OBJECTIVE: To compare prolapse recurrence and the incidence of mesh exposure between Restorelle® Y mesh and dual flat mesh. METHODS: A randomized trial of women undergoing laparoscopic (LSC) or robotic (RSC) sacrocolpopexy for post-hysterectomy vaginal prolapse. Subjects were randomized to either Y mesh or dual flat mesh. Subjects underwent a pelvic examination with POP-Q and evaluation of any mesh exposure, and the PFDI-20 was administered at 6, 12 and 24 months postoperatively. Subjective recurrence was defined by symptomatic vaginal bulge. All subjects underwent pelvic examination with POP-Q at 6, 12 and 24 months. Objective recurrence was defined by descent of the apex > 1/3 into the vaginal canal, anterior or posterior vaginal descent beyond the hymen, or retreatment for prolapse. RESULTS: Sixty-two patients were enrolled, and 59 patients were implanted with mesh: 30 Y mesh (17 LSC, 13 RSC) and 29 flat mesh (18 LSC, 11 RSC). There were no differences in patient characteristics between the groups. At 24 months, data were available for 44 (74.5%) patients. There were no mesh exposures for all subjects. PFDI-20 scores improved significantly for all subjects with no differences in mean improvement by mesh configuration. There were no differences in subjective and objective recurrence rates between the groups. Four patients (9.1%) complained of subjective vaginal bulge symptoms while nine (20.5%) patients had an objective recurrence (77.8% [7] examination only and 22.2% [2] reoperation). There were no apical recurrences. Of those patients who had a recurrence on examination only (n = 7), 85.7% (6) were asymptomatic. CONCLUSIONS: At 24 months, there were no differences in subjective outcomes and prolapse recurrence in patients who underwent sacrocolpopexy with the Restorelle® Y mesh versus dual flat mesh. One in five patients experienced an objective recurrence; however, there were no apical recurrences and the majority were asymptomatic.

Ferrante, K. L., et al. (2021). "Do Women Who Self-report More Exercise Have Increased Rates of Symptomatic Stress Urinary Incontinence After Midurethral Slings?" Female Pelvic Medicine & Reconstructive Surgery 27(1): e202-e207.
	OBJECTIVES: There is a paucity of data on postoperative exercise and how it relates to surgical failure, specifically after midurethral sling (MUS) surgery. We aimed to assess if women with higher self-reported activity levels as measured by strenuous exercise are more likely to experience stress urinary incontinence (SUI) symptoms after MUS than women with lower self-reported activity. METHODS: This is a secondary analysis of Operations and Pelvic Muscle Training in the Management of Apical Support Loss: the OPTIMAL Trial, a randomized trial comparing sacrospinous ligament suspension versus uterosacral ligament suspension, both with concomitant retropubic MUS. Participants completed a validated assessment of activity preoperatively and postoperatively. Women in the upper quartile for strenuous exercise (≥90 minutes per week) were compared with the remaining participants. Symptomatic SUI was defined as retreatment or reoperation for SUI and/or any positive response to Pelvic Floor Disorders Inventory stress incontinence questions 20 to 22. RESULTS: A total of 351 participants in the OPTIMAL study received MUS along with their prolapse repair and had postoperative exercise and Pelvic Floor Disorders Inventory data. At 2 years, 87 (29%) of 305 exercised strenuously for at least 90 minutes per week, and 63 (23%) of 277 experienced SUI. Women who were less active at 2 years were significantly more likely to experience SUI than women who were more active (26.6% vs 12.8%, P = 0.0138). CONCLUSIONS: In this study, symptomatic SUI occurred more frequently in women with lower self-reported exercise levels 2 years after MUS surgery.

Ferrari, F., et al. (2021). "Current Treatment Options for Cervical Leiomyomas: A Systematic Review of Literature." Medicina (Kaunas, Lithuania) 57(2).
	Background and objectives : Cervical leiomyomas are a rare benign disease. Although they are mainly treated surgically, currently, there is not a standardized treatment for cervical leiomyomas. This study aims to summarize current literature evidence about treatment options for cervical leiomyomas. Materials and methods : A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, including observational prospective and retrospective studies, case series and case reports. We collected data regarding studies related to treatment options for cervical leiomyomas, evaluating the following aspects: study design, population, treatment type, rate of surgical complications, and fertility outcome. Results : According to literature research, 38 articles were included. Among 214 patients, the weighted average age was 39.4 years-old; 23 patients were pregnant. Most of the leiomyomas (78%) were extracervical; in 22% of cases (29 patients) were intracervical; 188 patients (88%) received surgical treatment, 6 (3%) received exclusive conservative management and 21 (10%) underwent interventional radiology treatment. One hundred twenty-seven patients (67.5%) underwent myomectomy, while 54 (28.7%) and 7 (3.7%) hysterectomy and trachelectomy, respectively. Cervical myomectomy was performed by open surgery in 21 out of 127 cases (16.5%), while in 92 (72.4%) and 6 (4.7%) patients the surgical approach was performed by traditional and robot-assisted laparoscopy, respectively. The total rate of surgical complications was 5.6%. Conclusion : Surgery is the primary therapeutic option for cervical leiomyomas with a low rate of surgical complications. Interventional radiology techniques have reported promising but still limited results.

Ferraro, M. C., et al. (2023). "Ketamine and other NMDA receptor antagonists for chronic pain." Cochrane Database of Systematic Reviews(2).
	- Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of ketamine and other NDMA receptor antagonists compared to placebo, usual care, or other medicines for adults with chronic non‐cancer pain.

Ferreira, A., et al. (2023). "Does microfluidic sperm selection improve clinical pregnancy and miscarriage outcomes in assisted reproductive treatments? A systematic review and meta-analysis." PloS One 18(11): e0292891.
	Background: The microfluidic sperm selection (MFSS) device has emerged as a promising adjunct in assisted reproduction treatments (ART). It employs mechanisms of biomimicry based on the microanatomy of the female reproductive tract through strategies like chemotaxis and rheotaxis. Numerous studies assert improvements in ART outcomes with the use of MFSS, often attributed to the theoretical reduction in sperm DNA damage compared to other techniques. However, these attributed benefits lack validation through large-scale clinical trials, and there is no significant evidence of enhanced assisted reproductive treatments (ART) outcomes.; Objective: To evaluate whether the utilization of MFSS enhances clinical pregnancy results and abortion outcomes in couples undergoing ART compared to standard sperm selection techniques for Intracytoplasmic Sperm Injection (ICSI). We also assessed laboratory outcomes as a supplementary analysis.; Search Methods: We conducted searches across databases including PubMed, NIH, LILACS, CENTRAL, Crossref, Scopus, and OpenAlex. A total of 1,255 records were identified. From these, 284 duplicate records were eliminated, and an additional 895 records were excluded due to their association with patent applications, diagnostic tests, forensic analyses, or irrelevance to the research focus. Among the initially eligible 76 studies, 63 were excluded, encompassing abstracts, studies lacking adequate control groups, and ongoing clinical trials. Ultimately, 13 studies were selected for inclusion in the ensuing meta-analysis.; Results: Regarding clinical pregnancy, we assessed a total of 868 instances of clinical pregnancies out of 1,646 embryo transfers. Regarding miscarriage, we examined 95 cases of pregnancy loss among the 598 confirmed clinical pregnancies in these studies.; Conclusion: The utilization of MFSS demonstrates marginal positive outcomes compared to standard sperm selection techniques, without statistical significance in any of the analyses.; Broader Implications: This study conducted the first meta-analysis to evaluate clinical pregnancy rates, miscarriage rates, and laboratory results associated with the use of MFSS compared to standard sperm selection techniques. We have also listed potentially eligible studies for future inclusion. It's important to emphasize the need for multicenter studies with standardized parameters to attain a more robust clarification of this issue.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Ferreira Aderaldo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ferreira, P. A. G., et al. (2024). "Sublingual human chorionic gonadotropin as an adjuvant to ovulation induction." JBRA Assisted Reproduction.
	OBJECTIVE: To evaluate the efficacy of sublingually administered human chorionic gonadotropin (HCG) in combination with clomiphene citrate (CC) or letrozole (LTZ) for ovulation induction. METHODS: In this prospective, double-blind, randomized study, the patients were divided into two placebo groups and two intervention groups using CC, LTZ, and HCG. RESULTS: There were no statistically significant differences in ovulation induction between the groups. We compared endometrial thickness at the beginning of the cycle and during the pre-ovulatory period, and detected a moderately positive correlation when CC was administered with HCG. CONCLUSIONS: Sublingual HCG with CC caused a moderately positive correlation with endometrial thickening when compared with that at the beginning of the cycle and during the pre-ovulatory period. There was no significant change in the number of pre-ovulatory follicles.

Ferrero, S., et al. (2019). "Ulipristal Acetate before Hysteroscopic and Laparoscopic Surgery for Uterine Myomas: Help or Hindrance?" Gynecologic and Obstetric Investigation 84(4): 313-325.
	Background/aims: Ulipristal acetate ([UPA], Esmya®) is an orally active selective progesterone-receptor modulator that has been approved as preoperative treatment for uterine myomas. This systematic review aims to summarize the available data on surgical outcomes of patients undergoing myomectomy by hysteroscopy or by laparoscopy after preoperative treatment with UPA.; Methods: this review was performed following PRISMA guidelines and was registered in PROSPERO (CRD42018092201). PubMed, EMBASE, and Medline databases were systematically searched electronically until March 2018 for keywords concerning this topic. There were included only peer-reviewed, English language journal articles.; Results: two prospective studies and 4 retrospective studies were included. The effect of UPA on the endometrium does not increase the technical difficulty during hysteroscopic myomectomy, but it increases the chance of complete primary resection in complex hysteroscopic myomectomies. Moreover, UPA does not increase the overall technical difficulty of laparoscopic myomectomy. Contradictory results have been reported on the impact of UPA on the separation of the myoma from the myometrium and on the consistency of the myomas.; Conclusion: current results support the use of UPA prior to both surgical procedures. Further studies should confirm these preliminary findings and to assess the long-term outcomes of myomectomies following UPA treatment. (© 2018 S. Karger AG, Basel.)

Fethney, J., et al. (2024). "Evaluating a shared care pathway intervention for people receiving chemotherapy to reduce post-treatment unplanned hospital presentations: a randomised controlled trial." Supportive Care in Cancer 32(1): 77.
	Purpose: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care. Method(s): The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes. Result(s): The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02)). Conclusion(s): This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention. Trial registration: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014.Copyright © 2024, The Author(s).

fhfdt, R. B. R. (2023). "Effectiveness of Ozone Therapy Treatment of Endometriosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Participants will be randomly allocated into 2 groups (n = 30) via a computer system maintaining confidentiality with opaque, sealed and numbered envelopes. Control Group (CG): volunteers will undergo conventional drug treatment. Ozone Group (OZ): volunteers will undergo conventional drug treatment associated with ozone therapy. The experimental design of this research will consist of the initial assessment (general data, anthropometric measurements, weight, height, BMI, history of endometriosis and medication in use, intestinal alterations, urinary incontinence and dysmenorrhea) and socio‐demographic questionnaire. In addition, at the beginning and end of the research (10 weeks) the pain questionnaire (VAS), sexual function, quality of life (EHP‐30), Beck anxiety and depression inventory and brief COPE will be applied. These assessments will be scheduled in advance and will be carried out by a biomedical and medical collaborator of the work. In addition, the participant will be asked to complete a daily pain and menstrual flow questionnaire and, in every treatment session, the pain questionnaire will be applied before and after therapy. Blind uni masking process CONDITION: C12.100.250 Endometriosis PRIMARY OUTCOME: Evaluate pain during the 10 weeks of treatment and for 60 days after the applications, verified by the Visual Analog Scale screening. This performance is expected to assess whether there has been a reduction in pain based on the verification of a variation of at least 2 points in pre‐ and post‐intervention follow‐ups SECONDARY OUTCOME: Evaluate sexual function and quality of life during the 10 weeks of treatment and for 60 days after the applications, verified by the Endometriosis Health Profile Questionnaire (EHP‐30). It is expected to evaluate the improvement or not of the patient&apos;s sexual function and quality of life from the verification of a variation of at least 2 points of pre‐ and post‐intervention measurements. Evaluate the anxiety and the level of depression during the 10 weeks of treatment and for 60 days after the applications, verified by the Beck Hopelessness Scale and sessions of dealing with”, “overcoming”, “coping”, “taking care of”, “ endure” (short COPE). It is expected to evaluate the level of anxiety and the level of depression from the verification of a variation of at least 2 points of exercises pre and post‐intervention. INCLUSION CRITERIA: Women with Endometriosis with laboratory diagnosis; age group between 20 and 50 years; ability to respond to questionnaires; ability to consent to participation in the study and sign informed consent

Figueredo, J. M., et al. (2020). "Well-Being at Work after Return to Work (RTW): A Systematic Review." International Journal of Environmental Research and Public Health 17(20).
	BACKGROUND: Employees' well-being at work after the return to work (RTW) is considered a key aspect of rehabilitation and maintenance of workability. This systematic review aimed at identifying the common psychosocial factors that predict the subjective and psychological well-being in RTW processes after having a long-standing health problem or disability. OBJECTIVE: To evaluate the subjective and psychological well-being at work of employees with chronic or long-standing health problems or those returning to work after any cause of disability. DATA SOURCE: Systematic review of articles published in English or Spanish using PsycINFO, PsycARTICLES, MEDLINE, Psychology, and Behavioral Sciences Collection, and Pubpsych. An additional study was identified by contacting expert academics in the field. The search equations used included terms such as Return to Work, Long-Standing Health Problems or Disability, Work Health Balance, and job satisfaction or subjective well-being. Eligibility criteria for the studies: Studies that included a measure of employees' well-being at work following return to work were selected for the review. Evaluation of the studies and synthesis methods: The studies were selected using predefined fields which included quality criteria. RESULTS: Of the 264 articles returned by the initial search, a total of 20 were finally selected. Results were organized around the three different theoretical approaches for understanding RTW and its antecedents and consequences: (a) RTW and autonomy at work have a positive effect on psychological well-being; (b) job demand is linked to less job satisfaction, whereas a higher level on the work-health balance is associated with job satisfaction and work engagement; (c) internal and external support is linked to job satisfaction in the case of a disease. LIMITATIONS: The evidence provided by the results is restricted by the limited availability of studies focusing on well-being at work following return to work. Moreover, the studies identified are of different kinds, thereby preventing comparisons. Conclusions and implications of the main findings: Employees' subjective well-being after return to work has received very little attention to date. Given its importance in the current configuration of the labor market, it should be the object of more research.

Figueroa, E. and M. K (2020). "Psychological treatments to improve sex life in gynecological cancer survivors: Systematic review." Psicooncologia 17(2): 293-309.
	Objective: explore what psychological treatments can help gynecological cancer survivors to improve their sexual lives and intimate relationhips. Method(s): I searched the databases PubMed, Scopus, PsycInfo and MedLine, research between 2005 and 2020, focused on women survivors of gynecological cancer and treatments led by a mental health professional on the improvement of sexuality and intimate relationships in this population. Result(s): 10 articles were obtained (mixed design, randomized controlled trials and case studie) that involved psychological interventions focused on the improvement of sexuality and intimate relationships with women survivors of gynecological cancer. Conclusion(s): the psychoeducational intervention proved to be the most controlled intervention for the improvement of sexual function and reduction of sexual distress in women survivors of gynecological cancer.Copyright © 2020, Universidad Complutense de Madrid. All rights reserved.

Filippini, M., et al. (2021). "Postpartum perineal pain: may the vaginal treatment with CO 2 laser play a key-role in this challenging issue?" The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 34(8): 1190-1197.
	Purpose: Pregnancy and childbirth, despite being physiological events, represent a very delicate period in a woman's life, because they expose to important vulvo-perineal traumas. The pelvic pain that follows each delivery, whether spontaneous or surgical (caesarean section), does not end in the first days after birth but, depending on the studies, becomes persistent in a very variable percentage of cases. Therefore, in the present pilot study, we aimed, for the first time in literature, to assess the efficacy of CO 2 laser in women affected by perineal postpartum symptoms.; Materials and Methods: Between February 2013 and June 2018, all women with late postpartum pelvic pain referred to the Department of Obstetrics and Gynecology of San Marino Hospital, were recruited and treated using the CO 2 laser for three applications every 4-6 weeks.; Results: Between February 2013 and June 2018, according to the inclusion and exclusion criteria, 32 women with late postpartum pelvic pain were recruited in our protocol study. Mean age of patients was 34.1 years. At latest follow-up, our data demonstrated an improvement in symptoms (dyspareunia, pain at introitus, vaginal dryness, itching and vaginal burning) with a mean reduction of this symptom of 70% from baseline.; Conclusions: This study has shown the effectiveness of CO 2 laser treatment in postpartum perineal pain. Nevertheless, our results should be considered promising but preliminary. In fact, they need to be tested in larger cohort of patients to confirm its application in clinical practice and to evaluate the long-term duration of this treatment.

Filippini, M., et al. (2022). "CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis." The Journal of Sexual Medicine 19(3): 452-470.
	Background: Genitourinary syndrome of menopause (GSM) is a widespread condition with a great impact on quality of life and self-image.; Aim: We aimed to systematically review the current literature on CO2-Laser therapy efficacy for the treatment of GSM.; Methods: MEDLINE and Embase databases were systematically queried in December 2020 Studies included women with a diagnosis of Vulvo-Vaginal Atrophy (VVA) or GSM without an history of gynaecological and/or breast cancer, pelvic organ prolapse staged higher than 2, pelvic radiotherapy or Sjogren's Syndrome. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021238121.; Outcomes: Effects of CO2-Laser therapy on GSM symptoms assessed through subjective or objective efficacy measurement methods.; Results: A total of 803 articles were identified. Of these, 25 studies were included in this review for a total of 1,152 patients. All studies showed a significant reduction in VVA and/or GSM symptoms (dryness, dyspareunia, itching, burning, dysuria). The pooled mean differences for the symptoms were: dryness -5.15 (95% CI:-5.72,-4.58; P < .001; I 2 :62%; n = 296), dyspareunia -5.27 (95% CI:-5.93,-4.62; P < .001; I 2 :68%; n = 296), itching -2.75 (95% CI:-4.0,-1.51; P < .001; I 2 :93%; n = 281), burning -2.66 (95% CI:-3.75, -1.57; P < .001; I 2 :86%; n = 296) and dysuria -2.14 (95% CI:-3.41,-0.87; P < .001; I 2 :95%; n = 281). FSFI, WHIS and VMV scores also improved significantly. The pooled mean differences for these scores were: FSFI 10.8 (95% CI:8.41,13.37; P < .001; I 2 :84%; n = 273), WHIS 8.29 (95% CI:6.16,10.42; P < .001; I 2 :95%; n = 262) and VMV 30.4 (95% CI:22.38,38.55; P < .001; I 2 :24%; n = 68). CO2-Laser application showed a beneficial safety profile and no major adverse events were reported.; Clinical Implications: Vaginal laser treatment resulted in both a statistically and clinically significant improvement in GSM symptoms. FSFI improved significantly in all 8 included studies but it reached a clinically relevant level only in 2 of them.; Strengths & Limitations: The strength of the current meta-analysis is the comprehensive literature search. We reported data from a high number of patients (1,152) and high number of laser applications (more than 3,800). The main limitations are related to the high heterogeneity of the included studies investigating laser effects. Moreover, most of them are single center and nonrandomized studies.; Conclusion: The data suggest that CO2-Laser is a safe energy-based therapeutic option for the management of VVA and/or GSM symptoms in postmenopausal women; however, the quality of the body of evidence is "very low" or "low". Filippini M, Porcari I, Ruffolo AF, et al., CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:452-470. (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Filippo, A., et al. (2023). "Is TAP better than local anaesthetic wound infiltration for postoperative pain control in gynecological surgery: a systematic review and meta-analysis."
	
Fiol, G., et al. (2023). "Associations between Menopausal Hormone Therapy and Colorectal, Lung, or Melanoma Cancer Recurrence and Mortality: A Narrative Review." Journal of Clinical Medicine 12(16): 5263.
	Objective: to develop eligibility criteria for use in non-gynecological cancer patients. Method(s): We searched all the articles published in peer-reviewed journals up to March 2021. We utilized the PICOS standards and the following selection criteria: menopausal women with a history of non-gynecological and non-breast cancer who underwent hormone replacement therapy (HRT) using various preparations (oestrogens alone or in combination with a progestogen, tibolone, or tissue selective oestrogen complex) and different routes of administration (including oral, transdermal, vaginal, or intra-nasal). We focused on randomized controlled trials as well as relevant extension studies or follow-up reports, specifically examining recurrence and mortality outcomes. Result(s): Women colorectal cancer survivors who use MHT have a lower risk of death from any cause than those survivors who do not use MHT. Women who are skin melanoma survivors using MHT have a longer survival rate than non-MHT survivors. There is no evidence that women lung cancer survivors who use MHT have a different survival rate than those who do not use MHT. Conclusion(s): MHT is safe for women who have a history of colorectal, lung, or skin melanoma cancers.Copyright © 2023 by the authors.

Firdaoz, Y. (2023). "Effectiveness, safety and obedience of dienogest and leuprolide acetate in postlaparoscopic endometriosis patients." Journal of Obstetrics and Gynaecology Research 49: 47‐48.
	Objective: Comparing therapeutic effectiveness, safety profile, and adherence between Dienogest and postoperative Leuprolide Acetate in women with endometriosis who underwent laparoscopy. Methods: This study was a randomized clinical trial comparing the open label study to compare the effectiveness of therapy, safety profile, and obedience between postoperative dienogest and leuprolide acetate in women with endometriosis who underwent laparoscopy. Result: From the statistical test it was found that there was effectiveness of dienogest after 4 weeks of therapy (p = 0.004), after 8 weeks of therapy (p = 0.004) and after 12 weeks of therapy (p = 0.004). In the leuprolide acetate group it was also found that there was effectiveness of administration after 4 weeks of therapy (p = 0.004), after 8 weeks of therapy (p = 0.004) and after 12 weeks of therapy (p = 0.003). There was no difference in systolic blood pressure (p = 0.481), diastolic blood pressure (p = 1,000) and pulse frequency (p = 0.125) breath frequency (p = 1.000) and temperature (p = 0.236) between patients who received dienogest and leuprolide acetate. From the statistical analysis it was found that there were no differences in side effects in patients who received dienogest and leuprolide acetate (p = 0.238). Conclusion: There was no difference in therapeutic effectiveness, and the safety profile assessed by side effects as well as obedience of postoperative Dienogest and Leuprolide Acetate in endometriosis women undergoing Laparoscopy because in both groups there was a decrease in VAS scores from week to week.

Firmeza Mariana, A., et al. (2022). "The Effects of Hysterectomy on Urinary and Sexual Functions of Women with Cervical Cancer: A Systematic Review." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 44(8): 790-796.
	Objective: This systematic review aims at describing the prevalence of urinary and sexual symptoms among women who underwent a hysterectomy for cervical cancer.; Methods: A systematic search in six electronic databases was performed, in September 2019, by two researchers. The text search was limited to the investigation of prevalence or occurrence of lower urinary tract symptoms (LUTS) and sexual dysfunctions in women who underwent a hysterectomy for cervical cancer. For search strategies, specific combinations of terms were used.; Results: A total of 8 studies, published between 2010 and 2018, were included in the sample. The average age of the participants ranged from 40 to 56 years, and the dysfunctions predominantly investigated in the articles were urinary symptoms ( n = 8). The rates of urinary incontinence due to radical abdominal hysterectomy ranged from 7 to 31%. The same dysfunction related to laparoscopic radical hysterectomy varied from 25 to 35% and to laparoscopic nerve sparing radical hysterectomy varied from 25 to 47%. Nocturia ranged from 13%, before treatment, to 30%, after radical hysterectomy. The prevalence rates of dyspareunia related to laparoscopic radical hysterectomy and laparoscopic nerve sparing radical hysterectomy ranged from 5 to 16% and 7 to 19% respectively. The difficulty in having orgasm was related to laparoscopic radical hysterectomy (10 to 14%) and laparoscopic nerve sparing radical hysterectomy (9 to 19%).; Conclusion: Urinary and sexual dysfunctions after radical hysterectomy to treat cervical cancer are frequent events. The main reported disorders were urinary incontinence and dyspareunia.; Competing Interests: The authors have no conflict of interests to declare. (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Fischer, B., et al. (2021). "Assessment of the pelvic floor exercises with iPelvis® app. for treatment of women with urinary incontinence: a randomized controlled trial." Pelviperineology 40(3): 134‐144.
	Objective: To analyze the effectiveness of an application iPelvis® “app” for pelvic floor exercises, alone and associated with physiotherapy, in reducing urinary symptoms and improving the quality of life of incontinent women. Materials and Methods: This is a longitudinal randomized controlled clinical trial study. The Kings Health Questionnaire (KHQ) and the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF) were used as outcome measurements. The participants were divided into four groups: application + physiotherapy (AP + PHYSIO); home exercise sheet + physiotherapy (P + PHYSIO); only application (AP); only home exercise sheet (P). Results: From the 138 women who were evaluated, 77 (who presented a mean age of 48.31 years) completed the proposed treatments. In the KHQ domains and overall scores, the only ones who presented significant difference between groups were: the General Health Perception (P + PHYSIO higher than P, p=0.008), Social Limitations (P + PHYSIO higher than AP, p=0.04; P higher than AP, p=0.05) and Part I Score (P + PHYSIO higher than P, p=0.04). The analysis of the ICIQ‐SF showed P + PHYSIO higher than P (p=0.01). Between the other groups there were no significant differences. The other nine variables analysed no significant differences in all groups. Conclusion: The use of the application alone and associated with physiotherapy, produces better resulted in reducing urinary symptoms and improving the quality of life of incontinent women, in most variables, but it is not significantly superior in related to the other groups.

Fitz Victoria, W. and S. Mahalingaiah (2022). "Optimization of assisted reproductive technology outcomes in patients with polycystic ovarian syndrome: updates and unanswered questions." Current opinion in endocrinology, diabetes, and obesity 29(6): 547-553.
	Purpose of Review: Narrative review of recent literature on optimization of assisted reproduction technology outcomes in patients with polycystic ovarian syndrome (PCOS).; Recent Findings: The key areas of focus include pre cycle treatment with the goal of cohort synchronization, methods of ovulation suppression and trigger medication. There is no definitive evidence that precycle treatment with combined oral contraceptives (COCs) or progestins improve or negatively impact in vitro fertilization outcomes in patients with PCOS. The reviewed evidence supports consideration of progestins as suppression of premature ovulation in patients with PCOS as an alternative to gonadotropin releasing hormone (GnRH) antagonist if a freeze all protocol is planned. There is limited prospective evidence in PCOS populations regarding use of a dual trigger using GnRH agonist and human chorionic gonadotropin (hCG).; Summary: This review has implications for clinical practice regarding ovarian stimulation protocols for patients with PCOS. We also identified areas of research need including the further exploration of the value of pre cycle COC or progestin use in a PCOS population, also the use of GnRH agonist in combination with hCG in a well defined PCOS population and using GnRH agonist trigger alone as a control. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Five, L., et al. (2023). Delivering Transcutaneous Auricular Neurostimulation to Reduce Heavy Menstrual Bleeding in Von Willebrand Disease Patients.
	No Results Available Device: Volta System Blood loss during menses in von Willebrand Disease patients|Quality of Life of von Willebrand Disease patients|Duration and severity of dysmenorrhea in von Willebrand Disease patients|Duration of menstruation in von Willebrand Disease patients Female Not Applicable 10 Industry Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 5L-BLD-05 June 2024

fjx2jp, R. B. R. (2021). "Hormonal clinical treatment in deep endometriosis." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The active intervention in this work consists of dividing an experimental group of 40 women into 2 subgroups. Experimental group 1: 20 women with deep and intestinal endometriosis who will be treated with oral medication (z30.8 dienogest ‐ progestogen to treat endometriosis). Experimental group 2: 20 women with deep and intestinal endometriosis who will be treated with an intrauterine levonorgestrel device (Z30.1). The choice of drug treatment was offered at random (drawing / envelope). These two groups will be followed for 6 months. We can consider the application of two quality of life questionnaires as another intervention. Being SF36 and EHP30. Both questionnaires will be applied before starting medical drug treatment and 6 months after using them. During this 6‐month interval, these patients will be followed up monthly at the clinic to assess how they are with the medication and its side effects. Everything will be filed in medical records. Z30.8 CONDITION: Deep endometriosis; endometriosis; pelvic peritoneum endometriosis PRIMARY OUTCOME: Clinically assess quality of life in two groups of patients with deep endometriosis over a six‐month period, using levonorgestrel iodine and progestin via the oral route, using the questionnaires: SF36 and EHP30 quality of life assessment. Being carried out before and after using the medication. SECONDARY OUTCOME: As a side effect, we could consider both the benefits and the side effects of the two medications: oral progestogen and levonogestrel implantation. The benefits would be the improvement in pain. And the side effects would be irregular bleeding and non‐tolerability to the medication INCLUSION CRITERIA: Women with clinical diagnosis of deep endometriosis; no hormone use for at least 3 months prior (wash out); who are patients of the Gynecology and Obstetrics Department of Santa Casa de Misericórdia de São Paulo, at the endometriosis clinic and who are on a waiting list for surgical treatment

Flandin-Cretinon, S., et al. (2019). "Assessment of pelvic floor muscle training programs and urinary incontinence in women: A literature Review." Gynecologie Obstetrique Fertilite et Senologie 47(7-8): 591-598.
	Objectives: Pelvic floor rehabilitation is efficient for the first line treatment of urinary incontinence in women. However, several questions remain as regards the best pelvic floor muscle training program to recommend. The objective was perform a literature review regarding the muscular strengthening program to recommend to treat stress or mixed urinary incontinence in women. Method(s): We performed a systematic review of studies on the topic using Medline's database covering the 10 last years. Among the 1130 articles that were identified, we retained 6 for our analysis. Result(s): Given the heterogeneity of the exercise programs, it was impossible to exhaustively and comparatively analyze their efficacies. However, a significant improvement is noted when the exercises are based on the muscular training principles of the American College of Sports Medicine. They combine long and short contractions with the practice of the knack in situations of pressure exertion and are part of a self-rehabilitation program based on the needs of the patient and the individual's progression. Conclusion(s): Current knowledge does not allow us to recommend an optimal muscle training program to treat female urinary incontinence. Research must be conducted to evaluate different muscular training regimens but also their integration into a program based on personal needs as well as factors of adherence to the treatment of patients.Copyright © 2019 Elsevier Masson SAS

Flatman, L. K., et al. (2024). "Tumour necrosis factor inhibitors and serious infections in reproductive-age women and their offspring: a narrative review." Scandinavian Journal of Rheumatology.
	Tumour necrosis factor inhibitors (TNFi) are commonly used to treat patients with chronic inflammatory diseases, and function by inhibiting the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). Although beneficial in reducing disease activity, they are associated with an increased risk of serious infections. Data on the risk of serious infections associated with TNFi use during the reproductive years, particularly in pregnancy, are limited. For pregnant women, there is an additional risk of immunosuppression in the offspring as TNFi can be actively transported across the placenta, which increases in the second and third trimesters. Several studies have explored the risk of serious infections with TNFi exposure in non-pregnant and pregnant patients and offspring exposed in utero, indicating an increased risk in non-pregnant patients and a potentially increased risk in pregnant patients. The studies on TNFi-exposed offspring showed conflicting results between in utero TNFi exposure and serious infections during the offspring's first year. Further research is needed to understand differential risks based on TNFi subtypes. Guidelines conditionally recommend the rotavirus vaccine before 6 months of age for offspring exposed to TNFi in utero, but more data are needed to support these recommendations because of limited evidence. This narrative review provides an overview of the risk in non-pregnant patients and summarizes evidence on how pregnancy can increase vulnerability to certain infections and how TNFi may influence this susceptibility. This review focuses on the evidence regarding the risk of serious infections in pregnant patients exposed to TNFi and the risk of infections in their offspring.Copyright © 2024 Scandinavian Journal of Rheumatology Foundation.

Flatow, V., et al. (2023). "Skeletal muscle relaxants for the treatment of myofascial pelvic pain and high tone pelvic floor disorders." Current opinion in obstetrics & gynecology 35(4): 311-315.
	Purpose of Review: Chronic pelvic main is a complex process that includes many causes. In gynecology, the treatment of myofascial pelvic pain and high tone pelvic floor disorders can be managed with skeletal muscle relaxants for select clinical indications. A review of skeletal muscle relaxants will be included for gynecologic indications.; Recent Findings: There are limited studies on vaginal skeletal muscle relaxants, but there can be oral forms used for chronic myofascial pelvic pain. They function as antispastic, antispasmodic, and combination of the two modes of action. Diazepam is the most studied for myofascial pelvic pain in both oral and vaginal formulations. Its use can be combined with multimodal management to optimize outcomes. Other medications have limitations due to dependency and limited studies that demonstrate improvement in pain scales.; Summary: Skeletal muscle relaxants have limited high quality studies for chronic myofascial pelvic pain. Their use can be combined with multimodal options to improve clinical outcomes. Additional studies are needed for vaginal preparations and evaluation of safety and clinical efficacy for patient reported outcomes measures in patients living with chronic myofascial pelvic pain. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fleischer, K. and G. Thiagamoorthy (2020). "Pelvic organ prolapse management." Post Reproductive Health 26(2): 79-85.
	Pelvic organ prolapse describes the loss of support and subsequent descent of pelvic organs into the vagina. It is common, affecting up to 50% of parous women, and can be accompanied by a number of burdening symptoms. Prolapse has been thrown into the spotlight secondary to mesh-related complications. There are a number of effective treatment options to consider when managing pelvic organ prolapse and most do not require mesh. Patients' choice, comorbidities and likelihood of treatment success should be considered when making decisions about their care. Vaginal mesh surgery is currently on hold in the UK and even prior to this there has been a reduction both in the number of all prolapse surgeries and the number of women seeking surgery to manage their symptoms. This article reviews the current evidence for the management of pelvic organ prolapse, providing an update on the current state of mesh in prolapse surgery and summarises the key evidence points derived from the literature.Copyright © The Author(s) 2020.

Fleury, E. A. B., et al. (2021). "Interactive Music Therapy on Stress Level Reduction in Women Submitted to IVF/ICSI. Prospective Randomized Study." JBRA Assisted Reproduction 25(2): 209-214.
	OBJECTIVE: To identify the effects of interactive music therapy on stress levels in women undergoing high complexity infertility treatments. METHODS: Prospective randomized study involving 113 women treated in the Reproduction Human Laboratory of the Clinics Hospital of the Federal University of Goiás State, submitted to in vitro fertilization/intracytoplasmic sperm injection. We used Depression, Anxiety and Stress Scale, and Lipp's Stress Symptoms Inventory for Adults. In the Intervention Group, we used small and easy to play percussive musical instruments, a guitar, voice, and a recorder. We used interactive music therapy approach individually, applied before baseline ultrasound scan, oocyte pick-up, and embryo transfer. We analyzed the data using the R. Paired Student t-test to compare the results. RESULTS: Comparison of the stress levels by Depression, Anxiety and Stress Scale between the groups in the final moment of data retrieval resulted in 23.13 (SD±10.51; n=32) in the Control Group and 16.12 (SD±7.87; n=33) in the Intervention Group, being statistically different (p=0.004). Also in Lipp's Stress Symptoms Inventory for Adults there was a significant stress reduction in 39% of the patients in the Intervention Group compared to a reduction of 14% in the patients of the Control Group (p=0.032). In this same measurement resulted that only 3% of the Intervention Group patients versus 23% of the Control Group patients (p=0.027) were in the exhaustion stage. CONCLUSION: Interactive music therapy was effective for stress reduction in women during assisted reproduction techniques.

Flint, R., et al. (2019). "Rationale and design for fractional microablative CO 2 laser versus photothermal non-ablative erbium:YAG laser for the management of genitourinary syndrome of menopause: a non-inferiority, single-blind randomized controlled trial." Climacteric : the journal of the International Menopause Society 22(3): 307-311.
	Genitourinary syndrome of menopause (GSM) is a common condition affecting up to 50% of postmenopausal women and up to 70% of postmenopausal breast cancer survivors. GSM is a chronic condition with a significant impact on sexual health and quality of life. The mainstay of treatment has been with symptomatic relief using topical emollients or lubricants. Second-line treatment is with topical vaginal estrogens to restore the physiology of the vaginal epithelium. For some, the latter is not suitable or acceptable. Newer treatments with ospemifene and vaginal lasers have now been introduced. The two main types of laser currently used for the treatment of GSM are the fractional microablative CO 2 laser and the non-ablative photothermal erbium:YAG laser. We present a study protocol for a multicenter, prospective, non-inferiority, single-blinded, randomized controlled trial comparing the fractional microablative CO 2 laser versus the photothermal non-ablative erbium:YAG laser for the management of GSM. We will recruit 88 postmenopausal women across two sites who will be randomized to one of the two laser groups. Participants will all have GSM symptoms and a Vaginal Health Index Score < 15. All participants will receive an active treatment. Each participant will receive three applications of vaginal laser 1 month apart and will be followed up at 1 month, 6 months, and 12 months. Our primary outcomes will look at all changes of GSM symptoms (dryness, dyspareunia, itching, burning, dysuria, frequency, urgency), urinary incontinence (if present), and overall sexual satisfaction. Both subjective and objective means will be used to assess participants. The findings of this trial have the potential to allow clinicians and women suffering from GSM to make an informed decision when opting for a specific laser type. The trial will add to the current growing body of evidence for the safe use of vaginal lasers in GSM as an alternative treatment. We hope this trial will provide robust and long-term data for the safe use of both lasers.

Flor-Alemany, M., et al. (2022). "Exercise, Mediterranean Diet Adherence or Both during Pregnancy to Prevent Postpartum Depression-GESTAFIT Trial Secondary Analyses." International Journal of Environmental Research and Public Health 19(21).
	Targeting lifestyle behaviors during pregnancy is crucial to prevent the highly prevalent postpartum depression and its consequences. In these secondary analyses of an intervention trial to investigate the effects of concurrent exercise training on postpartum depression, we aimed to investigate the potential role of Mediterranean diet (MD) adherence on the exercise effects. A total of 85 pregnant women met the per-protocol criteria (exercise n = 46, control n = 39). The exercise program was delivered in 60 min sessions, 3 days/week, from the 17th gestational week until birth. Women's dietary habits were assessed with a food frequency questionnaire. The Mediterranean Food Pattern (an MD index) was derived from it to assess MD adherence. We used the Edinburgh Postnatal Depression Scale to assess postpartum depression. The postpartum depression score was not statistically different between control and exercise groups ( p > 0.05). A higher consumption of fruits (β = -0.242, p = 0.022), lower intake of red meat and subproducts (β = 0.244, p = 0.020), and a greater MD adherence (β = -0.236, p = 0.027) were associated with lower levels of postpartum depression. Greater adherence to the MD during pregnancy was associated with fewer depressive symptoms and a lower risk of postpartum depression. Postnatal depression was not reduced by prenatal exercise. Promoting fruit consumption while controlling the intake of red meat during pregnancy might prevent postnatal depression.

Flores-Lovon, K., et al. (2023). "Effects of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis: a systematic review." BMJ Open 13(9): e070456.
	Objectives: To evaluate the efficacy of antituberculosis therapy on pregnancy outcomes in infertile women with genital tuberculosis.; Design: Systematic review.; Data Sources: We searched in PubMed/MEDLINE, CENTRAL and EMBASE up to 15 January 2023. Additionally, we manually search the reference lists of included studies.; Eligibility Criteria: We included randomised controlled trials (RCT), non-RCTs (non-RCT) and cohort studies that evaluated the effects of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis compared with not receiving antituberculosis treatment or receiving the treatment for a shorter period.; Data Extraction and Synthesis: Two independent reviewers extracted data. We used Cochrane Risk of Bias 1.0 and Risk Of Bias In Non-randomised Studies tools for risk of bias assessment and meta-analysis was not performed. We used Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of the evidence.; Results: Two RCTs and one non-RCT were included. The antituberculosis regimens were based on isoniazid, rifampicin, pyrazinamide and ethambutol for 6-12 months. In women without structural damage, very low certainty of evidence from one RCT showed that the antituberculosis treatment may have little to no effect on pregnancy, full-term pregnancy, abortion or intrauterine death and ectopic pregnancy, but the evidence is very uncertain. In women with structural damage, very low certainty of evidence from one non-RCT showed that the antituberculosis treatment may reduce the pregnancy rate (297 fewer per 1000, 95% CI -416 to -101), but the evidence is very uncertain. In addition, very low certainty of evidence from one RCT compared a 9-month vs 6-month antituberculosis treatment regimen showed similar effects between the schemes, but the evidence is very uncertain. Two RCTs reported that no adverse events of antituberculosis treatment were noted or were similar in both groups.; Conclusion: The effect of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis is very uncertain.; Prospero Registration Number: CRD42022273145.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Florida University of, S. (2022). Vaginal Estradiol Use in Pessary Care.
	No Results Available Drug: Estradiol vaginal cream Pessary Discontinuation Rates|Phone calls/messages|Unscheduled office visits|Vaginal Bleeding|Pessary Discomfort|Vaginal Discharge|Urinary Tract Infection Rates|Vaginal Erosion Rates Female Early Phase 1 11 Other Allocation: Randomized|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care STUDY004394 April 26, 2023

Floyd, R., et al. (2022). "The Effect of Time-Restricted Eating on Insulin Levels and Insulin Sensitivity in Patients with Polycystic Ovarian Syndrome: A Systematic Review." International Journal of Endocrinology 2022: 2830545.
	Results: 2662 papers were identified with 37 selected for full-text review and one paper meeting criteria for inclusion. Ramadan fasting was the only time-restricted eating regimen trialled in this population with no strong evidence of a significant effect on insulin levels.; Conclusion: As the systematic review retrieved only one study investigating time-restricted eating to reduce insulin in patients with PCOS, there is no evidence to suggest that this intervention is effective. From the narrative review, based on studies in other patient groups, time-restricted eating could improve insulin resistance in those with PCOS; however, well-designed studies are required before this intervention can be recommended.; Competing Interests: The authors declare that there are no conflicts of interest. (Copyright © 2022 R. Floyd et al.)

Flynn, A. N., et al. (2021). "Timing and efficacy of mifepristone pretreatment for medical management of early pregnancy loss." Contraception 103(6): 404-407.
	OBJECTIVES: To determine the time interval between mifepristone and misoprostol administration associated with the most efficacious early pregnancy loss (EPL) management. STUDY DESIGN: We performed a secondary analysis of a randomized trial. Participants with EPL were instructed to take 200 mg oral mifepristone followed by 800 mcg vaginal misoprostol 24 hours later. The primary outcome was gestational sac expulsion at the first follow-up visit (1-4 days after misoprostol use) after a single dose of misoprostol and no additional intervention within 30 days after treatment. Despite specification of drug timing, participants used the medication over a range of time. We graphed sliding average estimates of success and assessed the proportion of treatment successes over time to define timing interval cohorts for analysis. We used multivariable generalized linear regression to assess the association between time interval and success. RESULTS: Of 139 eligible participants, 70 (50.4%) self-administered misoprostol before 24 hours, and 69 (49.6%) at or after 24 hours. We defined the following time intervals: 0 to 6 hours (n = 22); 7 to 20 hours (n = 29); and 21 to 48 hours (n = 88). Success occurred in 96.6% of the 7- to 20-hour cohort compared to 54.6% and 87.5% of the cohorts self-administering misoprostol earlier or later, respectively. When adjusting for race, gestational age, diagnosis, bleeding at presentation, insurance status, and enrollment site, participants administering misoprostol between 0 and 6 hours (adjusted risk ratio 0.58, 95% CI 0.40-0.85) and 21 to 48 hours (adjusted risk ratio 0.91, 95% CI 0.72-0.99) had a lower risk of success when compared to participants administering 7 to 20 hours after mifepristone. CONCLUSIONS: These data suggest that medical management of EPL has the highest likelihood of success when misoprostol is self-administered 7 to 20 hours after mifepristone. IMPLICATIONS: These preliminary data suggest that patients have the highest likelihood of success when misoprostol is taken between 7 and 20 hours after mifepristone. In contrast with medical abortion, simultaneous medication administration may not be as effective as delayed. Future research is needed to confirm the optimal medication time interval.

Fogacci, F., et al. (2023). "Impact of anti-oestrogen therapy on lipoprotein(a) in postmenopausal women: a systematic review and meta-analysis of double-blind placebo-controlled clinical studies." Endocrine 80(2): 292-302.
	Purpose: The potential mechanisms of endocrine therapy for thrombosis remain currently unclear, and more studies are warranted for further investigation and elucidation. However, high plasma concentration of lipoprotein(a) (Lp(a)) is a recognized prothrombotic factor. The aim of our study was to systematically evaluate the effect of different anti-oestrogen therapy on plasma Lp(a) level in postmenopausal women.; Methods: A systematic literature search was conducted in multiple electronic databases to identify the randomized, double-blind, placebo-controlled clinical studies on this topic. Effect size for changes in Lp(a) was expressed as mean difference (MD) and 95% confidence intervals (CI).; Results: Data were pooled from 10 clinical trials comprising 24 treatment arms, which included 2049 women (1128 women in the active-treated arms and 921 women in the control arms). Meta-analysis of data suggested that anti-oestrogen therapy in women significantly reduced Lp(a) [MD = -5.92% (95%CI: -9.05%,-2.8%)].; Conclusions: This observation is of both clinical and pathophysiological relevance, also in view that the identification of molecular determinants and cellular pathways implicated in Lp(a) synthesis and metabolism is still of concern as a critical issue in lipidology and CV prevention. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Foglietta, F., et al. (2023). "Ultrasound boosts doxorubicin efficacy against sensitive and resistant ovarian cancer cells." European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 183: 119-131.
	Ovarian cancer (OC) is characterised by the highest mortality of all gynaecological malignancies, frequent relapses, and the development of resistance to drug therapy. Sonodynamic therapy (SDT) is an innovative anticancer approach that combines a chemical/drug (sonosensitizer) with low-intensity ultrasound (US), which are both harmless per sé, with the sonosensitizer being acoustically activated, thus yielding localized cytotoxicity often via reactive oxygen species (ROS) generation. Doxorubicin (Doxo) is a potent chemotherapeutic drug that has also been recommended as a first-line treatment against OC. This research work aims to investigate whether Doxo can be used at very low concentrations, in order to avoid its significant side effects, as a sonosensitiser under US exposure to promote cancer cell death in Doxo non-resistant (A2780/WT) and Doxo resistant (A2780/ADR) human OC cell lines. Moreover, since recurrence is an important issue in OC, we have also investigated whether the proposed SDT with Doxo induces immunogenic cell death (ICD) and thus hinders OC recurrence. Our results show that the sonodynamic anticancer approach with Doxo is effective in both A2780/WT and A2780/ADR cell lines, and that it proceeds via a ROS-dependent mechanism of action and immune sensitization that is based on the activation of the ICD pathway.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fondazione Irccs Ca' Granda, O. M. P., et al. (2021). IVF Versus Surgery for Endometriosis Related Infertility.
	No Results Available Procedure: Surgery|Procedure: IVF Live birth rate from pregnancies started within 12 months since randomization|Cost-effectiveness evaluation of the two different approaches in the treatment of endometriosis|Detachment of inflammatory mediators that might interfere with IVF through analysis of extracellular vescicles (EV). Female Not Applicable 206 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ENDO-2020-23670289 January 31, 2025

Font Fundación Santiago, D. and U. Dexeus Institut (2021). Dual Trigger for Elective Fertility Preservation.
	No Results Available Drug: Ovulation triggering with GnRH-a+rhCG|Drug: Ovulation triggering with GnRH-a Number of mature oocytes (MIIs) retrieved|Number of oocytes retrieved|Change in Progesterone values|Change in Estradiol values|Change in FSH values|Change in LH values|Ovarian hyperstimulation syndrome (OHSS) (percent) Female Phase 4 136 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment FSD-PSE-2021-09|2021-002467-22 April 25, 2023

Fontes Adriana, F. S., et al. (2023). "Influence of metformin on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials." European Journal of Clinical Pharmacology 79(4): 445-460.
	Purpose: To summarize the effects of metformin treatment on markers of hyperandrogenism in patients diagnosed with polycystic ovary syndrome (PCOS).; Methods: A systematic review, with meta-analysis, of randomized placebo-controlled clinical trials that evaluated the effects of metformin treatment in adult patients with PCOS on the levels of hyperandrogenism markers was conducted. The literature search, data extraction, risk of bias, and the assessment of certainty of evidence were performed independently by two reviewers using a structured form. The results were combined by applying the random effect, and the effect measure presented as a standardized mean difference (SMD). Significant values were considered as p < 0.05 with 95% CI. Furthermore, sensitivity analyses were performed in order to explore possible heterogeneity between studies.; Results: Were included 18 studies in the quantitative evaluation and 17 studies (23 reports) in the quantitative evaluation. A significant reduction in total testosterone levels was seen in the metformin-treated group when compared to the control group after combining the results by the sensitivity analysis [SMD: - 0.46 (95% CI: - 0.89 to - 0.02)]. Therefore, FAI values were also regulated by metformin treatment.; Conclusion: We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was registered at Prospero (CRD42021235761). (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fordham, T. M., et al. (2024). "Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity." Obesity.
	Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS. Method(s): A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.3 +/- 6.5 kg/m2, age 15.6 +/- 1.3 years). Liver fat, very low-density lipoprotein (VLDL) lipogenesis, and triacylglycerol (TG) metabolism were measured following each 28-day phase of placebo or EAA. Result(s): Compared to placebo, EAA was associated with no difference in body weight (p = 0.673). Two markers of liver health improved: HS was lower (-0.8% absolute, -7.5% relative reduction, p = 0.013), as was plasma aspartate aminotransferase (AST) (-8%, p = 0.004). Plasma TG (-9%, p = 0.015) and VLDL-TG (-21%, p = 0.031) were reduced as well. VLDL-TG palmitate derived from lipogenesis was not different between the phases, nor was insulin sensitivity (p > 0.400 for both). Surprisingly, during the EAA phase, participants reported consuming fewer carbohydrates (p = 0.038) and total sugars (p = 0.046). Conclusion(s): Similar to studies in older adults, short-term EAA supplementation in adolescents resulted in significantly lower liver fat, AST, and plasma lipids and thus may prove to be an effective treatment in this population. Additional research is needed to elucidate the mechanisms for these effects.Copyright © 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.

Foreste, V., et al. (2021). "Hysteroscopy and retained products of conception: An update." Gynecology and Minimally Invasive Therapy 10(4): 203-209.
	Retained products of conception (RPOC) can occur after early or mid-trimester pregnancy termination and also following vaginal or cesarean delivery. It is frequently associated with continuous vaginal bleeding, pelvic pain, and infection. Late complications include intrauterine adhesions formation and infertility. Conventionally, the management of RPOC has been with blind dilation and suction curettage (D and C); however, hysteroscopic resection of RPOC is a safe and efficient alternative. In this review, we analyze the current available evidence regarding the use of hysteroscopic surgery for the treatment of RPOC comparing outcomes and complications of both traditional curettage and hysteroscopic technique. Data search has been conducted using the following databases MEDLINE, EMBASE, Web of Sciences, Scopus, Clinical Trial. Gov., OVID, and Cochrane Library interrogate all articles related to hysteroscopy and the preserved product of conception, updated through September 2020.Copyright © 2021 Wolters Kluwer Medknow Publications. All rights reserved.

Forget-Renaud, A., et al. (2021). "An Interdisciplinary Program Promoting the Adoption of a Healthy Lifestyle Increases Insulin Sensitivity in Women With Obesity and Infertility." Canadian journal of diabetes 45(7): S17‐S18.
	Insulin resistance contributes to the pathogenesis of polycystic ovary syndrome and may play a role in obesity‐associated infertility. Since lifestyle modifications are recommended in women affected by these conditions, we hypothesize that such modifications may increase their insulin sensitivity. Methods: Women with obesity and infertility were randomly allocated to usual fertility care (control group, CG) or a lifestyle intervention (LSG) alone for 6 months and then combined with standard care. Insulin resistance was estimated during fasting (HOMA‐IR) and a 75g oral glucose tolerance test (Matsuda Insulin Sensitivity Index, ISI(M)) in women not taking medication affecting insulin sensitivity (except metformin). Data were collected at baseline, 6, 12 and 18 months, and as soon as possible when the participant knew she was pregnant. We estimated the integrated change in insulin sensitivity during follow up, using the incremental area‐under‐the‐curve divided by time (iAUC‐ISI(M)/time). Results: Among 130 randomized participants, 106 had available data (LSG=51, CG=55). As compared to CG, women in the LSG improved significantly their ISI(M) after 6 months (+0.23±1.05 vs ‐0.33±1.53, p=0.045, n=90), as well as their iAUC‐ISI(M)/time during follow up (+0.18±0.84 vs ‐0,21±0,93, p=0.035, n=104). This result remained statistically significant after correction for baseline BMI, age and use of folic acid. There was no impact on HOMA‐IR. Conclusion: An interdisciplinary program promoting the adoption of a healthy lifestyle significantly increases insulin sensitivity in women with infertility and obesity. It may be explained, in part, by the weight loss associated with the intervention and may have a role in improving fertility in this population.

Foroozanfard, F., et al. (2022). "Erratum: note of Concern: effects of Zinc Supplementation on Markers of Insulin Resistance and Lipid Profiles in Women with Polycystic Ovary Syndrome: a Randomized, Double-blind, Placebo-controlled Trial (Exp Clin Endocrinol Diabetes (2015) 123 DOI 10.1055/s-0035-1548790)." Experimental and clinical endocrinology & diabetes.
	Since publication of this article, serious concerns have been raised about the integrity of the reported methods, results and analysis. Responses by the leading author and ethics committees have been unsatisfactory and inconclusive; we advise readers to interpret the information presented in the article with due caution

Foroozanfard, F., et al. (2022). "Erratum: note of Concern: effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial (Horm Metab Res (2017) 49 DOI: 10.1055/s-0043-112346)." Hormone and metabolic research.
	Since publication of this article, serious concerns have been raised about the integrity of the reported methods, results and analysis. Responses by the leading author and ethics committees have been unsatisfactory and inconclusive; we advise readers to interpret the information presented in the article with due caution

Foschi, C., et al. (2022). "Vaginal metabolites in postmenopausal women with or without vulvo-vaginal atrophy at baseline and after ospemifeme and systemic hormone treatment." Maturitas 159: 7-14.
	Objectives: Vulvo-vaginal atrophy (VVA) is a highly prevalent chronic condition affecting the lives of postmenopausal women. Ospemifene and systemic hormone therapy (HT) improve vaginal health. This study aims to characterize the vaginal metabolic profile of women with VVA at baseline and after ospemifene and systemic HT.; Study Design: Sixty postmenopausal women, 32 of whom were affected by VVA, were consecutively enrolled. The vaginal metabolic profile of women with and without VVA at baseline and after three months of ospemifene or HT treatment was assessed.; Main Outcome Measures: The following parameters were evaluated: (i) the Vaginal Health Index; (ii) the Vaginal Maturation Index; and (iii) vaginal metabolic profile, by means of 1 H NMR spectroscopy.; Results: The vaginal metabolome of postmenopausal women with VVA was different from that of postmenopausal women without VVA, including a more profound decrease in the levels of lactate and several amino acids, typically found in eubiosis, together with an enrichment of molecules derived from anaerobes and gut microbes. After 3 months, ospemifene and HT had modified the vaginal metabolome of the women with VVA, specifically by increasing the levels of beneficial molecules (e.g., lactate, leucine, glycine) and reducing those involved in dysbiosis (e.g., formate). HT improved the vaginal metabolome to a lesser extent.; Conclusions: The vaginal metabolic profile of postmenopausal women with VVA differs from that of postmenopausal women without VVA. Our preliminary data show that both ospemifene and HT treatment increase the levels of molecules beneficial for vaginal health and reduce the levels of those involved in dysbiosis. HT improves the vaginal metabolic profile to a lower extent than ospemifene over the course of three months.; Competing Interests: MCM had past financial relationships (lecturer, member of advisory boards and/or consultant) with Shionogi Limited, Italfarmaco, MDS Italia, Bayer.MB had past financial relationships (consultant) with Shionogi Limited.All other authors declare that they have no competing interests. (Copyright © 2021. Published by Elsevier B.V.)

Fouad, S., et al. (2021). "Menopause anxiety and depression; how food can help?" Open Access Macedonian Journal of Medical Sciences 9: 64-71.
	BACKGROUND: Anxiety and depression are reported as two major frequent and chief complaints among peri-menopausal women in several societies. AIM: The objective of the study was to study the effect of using two dietary supplements to beat depression and anxiety associated with menopause. SUBJECTS AND METHODS: Sixty-six volunteers' menopausal women participated on the study for 8 weeks, 35 subjects consumed daily cookies prepared mainly from soya flour and flaxseed, and 31 females consumed daily a blend composed mainly of raw unroasted peanut and raw sesame. Follow-up was performed with menopause rating scale, anxiety score, depression score, and biochemical parameters. RESULT(S): Soya cookies were rich in plant-based protein and total phenols while blend was a good source of unsaturated fatty acid. Blend consumers showed significant percentage reduction in beck anxiety score and beck depression score after intervention, more than cookies consumers group. The anthropometrics parameters were statistical significant changed on both groups, more on the group who consumed the soya cookies. Soya cookies demonstrated an anti-inflammatory effect, while blend had an antioxidant and anti-inflammatory effects as was shown on the serum assay of interleukin-6 and malondialdehyde as an inflammatory marker and an antioxidant marker, respectively. CONCLUSION(S): From the results, it can be concluded that the supplementation of products enriched with unsaturated fatty acid was more beneficial to slow down the psychological menopause symptoms than natural estrogen rich product consumption. of women' menopause could develop a condition of.Copyright © 2021 Suzanne Fouad, Salwa M. El Shebini, Maha Abdel-Moaty, Nihad Hassan Ahmed, Ahmed Mohamed Saied Hussein, Hend Abbas Essa, Salwa T. Tapozada.

Foundation, G. O. G. and I. Foundation (2022). A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer.
	No Results Available Device: da Vinci|Other: open surgery Survival Female Not Applicable 840 Other Allocation: Randomized|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GOG-3043 August 2029

Foundation, G. O. G. and GlaxoSmithKline (2024). Heated Intraperitoneal Chemotherapy Followed by Niraparib for Ovarian, Primary Peritoneal and Fallopian Tube Cancer.
	Main Outcome Measure: Progression-free survival Secondary Outcome Measure: Overall Survival, Frequency and severity of adverse events etc. Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 3-4 cycles). Registered patients who progress during neoadjuvant chemotherapy will not be eligible for iCRS and will be removed from the study. Following completion of neoadjuvant chemotherapy, interval cytoreductive surgery (iCRS) will be performed in the usual fashion in both arms. Patients will be randomized at the time of iCRS (iCRS must achieve no gross residual disease or no disease >1.0 cm in largest diameter) to receive HIPEC or no HIPEC. Patients randomized to HIPEC (Arm A) will receive a single dose of cisplatin (100mg/m2 IP over 90 minutes at 42 C) as HIPEC. After postoperative recovery patients will receive standard post-operative platinum-based combination chemotherapy. Patients randomized to surgery only (Arm B) will receive postoperative standard chemotherapy after recovery from surgery. Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy per institutional standard (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 2-3 cycles) for a maximum total of 6 cycles of chemotherapy (neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing until progression or 36 months (if no evidence of disease).

Fox, R. S., et al. (2022). "Optimizing a Behavioral Sleep Intervention for Gynecologic Cancer Survivors: Study Design and Protocol." Frontiers in Neuroscience 16: 818718.
	Sleep difficulties, particularly symptoms of insomnia and circadian disruption, are among the primary complaints of gynecologic cancer survivors before, during, and after treatment. Moreover, difficulty sleeping has been linked to poorer health-related quality of life and elevated symptom burden in this population. Although leading behavioral sleep interventions have demonstrated efficacy among cancer survivors, up to 50% of survivors are non-adherent to these treatments, likely because these interventions require labor-intensive behavior and lifestyle changes. Therefore, there is a need for more effective and acceptable approaches to diminish sleep disturbance among cancer survivors. This manuscript describes the methodology of a two-part study guided by the Multiphase Optimization Strategy (MOST) framework to identify a streamlined behavioral sleep intervention for gynecologic cancer survivors. Three candidate intervention components previously shown to decrease sleep disturbance will be evaluated, including sleep restriction, stimulus control, and systematic bright light exposure. Participants will be adult women with a history of non-metastatic gynecologic cancer who have completed primary treatment and who report current poor sleep quality. Fifteen participants will be recruited for Part 1 of the study, which will utilize qualitative methods to identify barriers to and facilitators of intervention adherence. Results will inform changes to the delivery of the candidate intervention components to promote adherence in Part 2, where 80 participants will be recruited and randomized to one of eight conditions reflecting every possible combination of the three candidate intervention components in a full factorial design. Participants will complete assessments at baseline, post-intervention, and 3-months post-intervention. Part 2 results will identify the combination of candidate intervention components that yields the most efficacious yet efficient 6-week intervention for diminishing sleep disturbance. This is the first known study to apply the MOST framework to optimize a behavioral sleep intervention and will yield a resource-efficient treatment to diminish sleep disturbance, improve health-related quality of life, and decrease symptom burden among gynecologic cancer survivors. ClinicalTrials.gov Identifier: NCT05044975.Copyright © 2022 Fox, Gaumond, Zee, Kaiser, Tanner, Ancoli-Israel, Siddique, Penedo, Wu, Reid, Parthasarathy, Badger, Rini and Ong.

Fraga Mirian, V., et al. (2022). "Effect of Surgical Treatment for Deep Infiltrating Endometriosis on Pelvic Floor Disorders: A Systematic Review with Meta-analysis." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 44(5): 503-510.
	Objectives: To evaluate the impact of surgical treatment of deep infiltrative endometriosis (DIE) on pelvic floor dysfunction (urinary incontinence [UI], pelvic organ prolapse [POP], fecal incontinence [FI)] or constipation, and sexual function [dyspareunia]).; Data Source: The present systematic review was performed in the PubMed database. For the selection of studies, articles should be published by January 5, 2021, without language restriction.; Study Selection: Six randomized controlled studies that evaluated surgical treatment for DIE and the comparison of different surgical techniques were included.; Data Collection: The studies were selected independently by title and abstract by two authors. Disagreements were resolved by a third author. All included studies were also evaluated according to the Cochrane risk of bias tool and the quality of the evidence was analyzed using the GRADE criteria. Subgroup analysis by different treatments and follow-up periods was also performed.; Results: Six studies were included in the quantitative analysis. The risk of bias between studies showed an uncertain risk of bias for most studies, with concealment of allocation being the least reported category. The quality of the evidence was considered low. High heterogeneity was found between the studies. No study has evaluated UI or POP comparatively before and after surgery.; Conclusion: Dyspareunia and FI have improved after the surgical procedure, but it was not possible to demonstrate which surgical technique was related to these outcomes as there was surgical heterogeneity. This diversity was found across data, with the recommendation of future prospective studies addressing pelvic floor disorders with DIE.; Competing Interests: The authors have no conflict of interests to declare. (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Fraison, E., et al. (2019). "Pregnancy following diagnosis of premature ovarian insufficiency: a systematic review." Reproductive Biomedicine Online 39(3): 467-476.
	The aim of this review is to report the occurrence of pregnancies in women with premature ovarian insufficiency (POI), naturally or with different treatments (hormonal replacement therapy, IVF, in-vitro maturation and stem cell therapy). This study involved an exhaustive search of the electronic databases MEDLINE, PubMed and Embase covering the period January 2000 to January 2018. A combination of Medical Subject Heading and text words was used to generate a subset of citations, including studies involving POI ('premature menopause' or 'premature ovarian failure' or 'POI' or 'hypergonadotrophic amenorrhoea'). This subset of citations was then combined with 'AND' to the Medical Subject Heading term 'pregnancy'. Fifteen studies were included in this review. Two randomized controlled trials, two observational studies, and 11 interventional studies reporting cases of pregnancy in women with POI were included. This review reports pregnancy rates across studies ranging from 2.2% to 14.2%. Mean age in patients who achieved a pregnancy was 30 years, highlighting that oocyte quality in these patients is likely unaffected. No treatment has thus far shown its superiority in improving fertility in women with POI. Recent advances in options such as in-vitro maturation and stem-cell therapy, however, are likely to be the future of treatment and may generate new hope for these patients.Copyright © 2019 Reproductive Healthcare Ltd.

Francés-Herrero, E., et al. (2022). "Bioengineering trends in female reproduction: a systematic review." Human Reproduction Update 28(6): 798-837.
	Background: To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.; Objective and Rationale: This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.; Search Methods: A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.; Outcomes: Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.; Wider Implications: The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies. (© The Author(s) 2022. Published by Oxford Universit Press on behalf of European Society of Human Reproduction and Embryology.)

Francis Julie, A., et al. (2019). "No. 370-Management of Squamous Cell Cancer of the Vulva." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 41(1): 89-101.
	Objective: This guideline reviews the clinical evaluation and management of squamous cell cancer (SCC) of the vulva with respect to diagnosis, primary surgical, radiation, or chemotherapy management and need for adjuvant treatment with chemotherapy and/or radiation therapy. Other vulvar cancer pathologic diagnoses are not included in the guideline.; Intended Users: The first part of this document which includes recommendations 1 through 3 is for general gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers with a focus on the presentation, diagnosis, and updated information about surgical procedures performed by subspecialists. The surgical management and treatment of advanced vulvar cancer are intended for gynaecologic oncologists, radiation oncologists, and medical oncologists who treat these complex patients. This guideline is intended to provide information for interested parties who may follow these patients once treatment is complete.; Target Population: Adult women (18 years and older) with SCC of the vulva. Excluded from these guidelines are women with preinvasive disease.; Options: Women diagnosed with SCC of the vulva should be referred to a gynaecologic oncologist for initial evaluation, consideration for primary surgery and inguinal lymph node assessment, and potentially adjuvant radiation and/or chemotherapy. All cases of vulvar cancer should have access to discussion at a multidisciplinary cancer case conference. Women who would otherwise require radical surgery such as abdominal-perineal resection or exenterative procedures may be considered for primary treatment with radiation and/or chemotherapy.; Evidence: For this guideline, relevant studies were searched in PubMed, Medline, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials: vulva, vulvar cancer, inguinofemoral lymph node dissection, sentinel nodes, systemic chemotherapy, radiotherapy, neoadjuvant, adjuvant, primary, exenteration, survival, follow up. The initial search was performed in September 2016 with a final literature search in May 2017. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 286, and 78 studies were included in this review.; Validation Methods: The content and recommendations were drafted and agreed upon by the principal authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework (Table 1). The interpretation of strong and weak recommendations is described in Table 2. The Summary of Findings is available upon request.; Benefits, Harms, And/or Costs: These guidelines are to encourage physicians in the appropriate use of sentinel inguinal lymph node assessment for SCC of the vulva. The committee also promotes the centralization of treatment of vulvar cancer in specialized treatment centres.; Guideline Update: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.; Sponsors: This guideline was developed with resources funded by the Society of Gynecologic Oncology of Canada and the Society of Obstetricians and Gynaecologists of Canada.; Summary Statemen s: RECOMMENDATIONS. (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Francis, K. E., et al. (2021). "Reporting the trajectories of adverse events over the entire treatment course in patients with recurrent platinum-sensitive ovarian cancer treated with platinum-based combination chemotherapy regimens: a graphical approach to trial adverse event reporting." European journal of cancer (Oxford, England : 1990) 148: 251‐259.
	BACKGROUND: Clinical trials report adverse events (AEs) in a dense table focusing on the frequency of 'worst grade' AEs experienced over the duration of treatment. There is usually no granular information provided on the timing and trajectory of AEs or whether they are likely to worsen, improve, or remain constant over time. PATIENTS AND METHODS: Non‐hematologic (NH) AE data was extracted from the CALYPSO trial comparing carboplatin with pegylated liposomal doxorubicin (CD) to carboplatin with paclitaxel (CP) in recurrent ovarian cancer (ROC). Generalised estimating equations (GEE) were used to assess the risk and trajectory of combined Grade 2 or higher (G2+) AE and of each specific AE. The risk of G2+AE was also compared between treatment arms. RESULTS: The study included 976 patients and AE were reported for the duration of treatment. Most patients experienced at least one G2+NHAE (CP:CD, 96.0%:80.6%). Risk of combined G2+AE increased with CP (4.1% per‐cycle) but decreased with CD (0.8%, P <0.01). When alopecia and sensory neuropathy were excluded, risk of G2+ AE decreased by 2.7% per‐cycle, with no significant difference between treatment arms. G2+ nausea improved (15.2% per‐cycle, P <0.01). G2+ sensory neuropathy worsened (29.3% per‐cycle, P <0.01). Fatigue was stable (17% per‐cycle, P =0.06) whilst G2+ pain decreased over time (13.4% per‐cycle, P <0.01), with no difference between treatment arms. CONCLUSION: Existing trial data can be used to provide AE trajectories as illustrated here for ROC. These trajectories have utility in guiding treatment choice and potentially optimising AE management with novel therapies and treatment combinations.

Francis, K. E., et al. (2022). "The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer." Annals of oncology : official journal of the European Society for Medical Oncology 33(6): 593-601.
	Background: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration.; Patients and Methods: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks.; Results: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76).; Conclusions: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.; Competing Interests: Disclosure KEF reports intuitional funding from AstraZeneca (AZ). MF reports institutional funding from AZ, Novartis, and Beigene; consulting fees from AZ, Novartis, GlaxoSimthKline (GSK), Merck Sharp & Dohme (MSD), Takeda, and Lilly; honoraria for lectures from AZ, GSK, and ACT-Genomics; travel support from AZ; and participation in a data advisory role with Australasian Gastro-Intestinal Cancer Trials Group and Independent Data and Safety Monitoring Board. IRC reports personal fees and travel support from AZ, GSK, and Clovis Oncology; and personal fees from Roche, Mersana, Deciphera, Eisai, Amgen, Bristol Myers Squibb, OncXerna, and Aravive. AC reports institutional research funding from AZ; payment from Clovis Oncology for lectures and travel support; and he participates in an advisory role to AZ. RP reports institutional funding from AZ. He participates in an advisory role to AbbVie, AZ, Care4ward (unpaid), Clovis Oncology, Curio Science, Eisai Inc., Genentech, Janssen Oncology (J&J), Merck & Co., Mersana Therapeutics, Inc., NewLink Genetics, Nexus Global Group, Pieris Pharma Inc., Roche, Inc., Sutro Biopharma, Syndax Pharmaceuticals, Tesaro Inc., Vascular Biogenics Ltd. NC reports grants, consulting fees, and personal fees from AZ; consulting fees and personal fees from GSK; and personal fees from Tesaro, Novartis, Clovis, MSD, GSK, EISAI. She participates in an advisory role with Roche, PharmaMar, AZ, Clovis Oncology, MSD, GSK, Tesaro, Pfizer, BIOCAD, ImmunoGen, Mersana, OncXerna, and Eisai. KF reports institutional research funding and honoraria for lectures from AZ. GS reports institutional research funding from AZ, MSD, Novartis, and Roche; and consulting fees paid to the institution from BioViva and Segen. IV reports receiving institutional fees from Oncoinvent AS and Genmab; grant funding from Amgen and Roche; consulting fees from Aksebio, Amgen, GmbH, AZ, Clovis Oncology, Carrick Therapeutics, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Roche, Genmab, GSK, Immunogen Inc., Jazz Pharma, Karyopharm, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Novartis, Octimet Oncology NV, Oncoinvent AS, Sotio a.s., Verastem Oncology, Zentalis; and travel expenses from Amgen, MSD, Tesaro, AZ, Roche. EPL reports medical writing assistance for the primary SOLO2 publication from AZ; institutional grants from AZ and Merck; personal payments for lectures from AZ and GSK; and participation in an advisory role with Incyte, Roche, and Pfizer. He reports other interests including as an employee of ARCAGY GINECO research group. CKL reports institutional payments from Roche, AZ, and Merck KGA; and personal payments for lectures, presentations or travel support from AZ, Amgen, Takeda, Boehringer Ingelheim, Pfizer, Yuhan, Merck KGA, Roche, and MSD. All other authors have declared no conflicts of interest. (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Francischini Cristiane Raquel, D., et al. (2022). "Antitumor effects of oleandrin in different types of cancers: Systematic review." Toxicon : official journal of the International Society on Toxinology 216: 15-27.
	Oleandrin, a cardiac glycoside isolated from the leaves of Nerium oleander, has known effects on the heart. Evidence from recent studies have highlighted its potential for anticancer properties. Therefore, we aimed to investigate the effects of oleandrin on cancer cell proliferation, viability and apoptosis in vitro and in vivo. We performed a systematic search in six electronic databases up to Jan 2022. We extracted information about the effects of oleandrin on cell proliferation, cell viability, apoptosis and/or cell cycle arrest in in vitro studies, and the effects on tumor size and volume in animal experimental models. We have retrieved 775 scientific studies. 14 studies met the inclusion criteria. They investigated the effects of oleandrin on breast, lung, pancreatic, colon, prostate, colorectal, oral, ovarian, glioma, melanoma, glioblastoma, osteosarcoma, and histiocytic lymphoma cancers. Overall, in vitro studies demonstrated that oleandrin was able to inhibit cell proliferation, decrease cell viability, and induce apoptosis and/or cell cycle arrest. In addition, oleandrin had an effect on reducing mean tumor size and volume in animal studies. Oleandrin, as a cytotoxic agent, demonstrated antitumor effects in different types of cancers, however important clinical limitations remain a concern. These results encourage future studies to verify the applicability of oleandrin in antineoplastic therapeutic protocols human and veterinary medicine, the investigation of antimetastatic properties, as well as the potential increase in patient survival and the decrease of tumor markers. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Francisco, A.-C., et al. (2022). "A systematic review on the effectiveness of physical rehabilitation interventions to reduce symptom burden and improve quality of life in women with endometriosis and/or adenomyosis."
	
Francisco Javier, R., et al. (2021). "Uterine artery embolization of uterine arteriovenous malformation: a systematic review."
	
Francisco Phorenice, D., et al. (2022). "Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta-analysis." American journal of reproductive immunology (New York, N.Y. : 1989) 88(4): e13605.
	Problem: The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic.; Method of Study: A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random-effect meta-analysis was conducted using the software RevMan 5.4. Pre-planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted.; Results: Data from eight trials showed a statistically significant benefit of LIT (RR = 1.45, 95% CI 1.05-2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR = 1.34, 95% CI = .84-2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×10 6 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR = 1.97, 95% CI = 1.53-2.53).; Conclusion: LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity. (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Franciszek, D., et al. (2020). "Ovarian Cancer and Pregnancy-A Current Problem in Perinatal Medicine: A Comprehensive Review." Cancers 12(12): 1-18.
	The frequency of concomitant adnexal tumors in pregnancy is reported to be at 0.15-5.7%, while ovarian cancer complicates 1 in 15,000 to 1 in 32,000 pregnancies, being the second most common gynecologic cancer diagnosed during pregnancy. The aim of this review is to discuss the problem of ovarian cancer complicating pregnancy and the current recommendations for diagnostics and treatment, with an emphasis on the risk to the fetus. A detailed analysis of the literature found in the PubMed and MEDLINE databases using the keywords "ovarian cancer", "ovarian malignancy", "adnexal masses", "ovarian tumor" and "pregnancy" was performed. There were no studies on a large series of pregnant women treated for ovarian malignancies and the management has not been well established. The diagnostics and therapeutic procedures need to be individualized with respect to the histopathology of the tumor, its progression, the gestational age at the time of diagnosis and the mother's decisions regarding pregnancy preservation. The multidisciplinary cooperation of specialists in perinatal medicine, gynecological oncology, chemotherapy, neonatology and psychology seems crucial in order to obtain the best possible maternal and neonatal outcomes.

Franck, L. S., et al. (2023). "Maternal mental health after infant discharge: a quasi-experimental clinical trial of family integrated care versus family-centered care for preterm infants in U.S. NICUs." BMC pediatrics 23(1): 396.
	BACKGROUND: Involvement in caregiving and tailored support services may reduce the risk of mental health symptoms for mothers after their preterm infant's neonatal intensive care unit (NICU) discharge. We aimed to compare Family-Centered Care (FCC) with mobile-enhanced Family-Integrated Care (mFICare) on post-discharge maternal mental health symptoms. METHOD: This quasi-experimental study enrolled preterm infant (≤ 33 weeks)/parent dyads from three NICUs into sequential cohorts: FCC or mFICare. We analyzed post-discharge symptoms of perinatal post-traumatic stress disorder (PTSD) and depression using intention-to-treat and per protocol approaches. RESULTS: 178 mothers (89 FCC; 89 mFICare) completed measures. We found no main effect of group assignment. We found an interaction between group and stress, indicating fewer PTSD and depression symptoms among mothers who had higher NICU-related stress and received mFICare, compared with mothers who had high stress and received FCC (PTSD: interaction β=-1.18, 95% CI: -2.10, -0.26; depression: interaction β=-0.76, 95% CI: -1.53, 0.006). Per protocol analyses of mFICare components suggested fewer PTSD and depression symptoms among mothers who had higher NICU stress scores and participated in clinical team rounds and/or group classes, compared with mothers who had high stress and did not participate in rounds or classes. CONCLUSION: Overall, post-discharge maternal mental health symptoms did not differ between the mFICare and FCC groups. However, for mothers with high levels of stress during the NICU stay, mFICare was associated with fewer post-discharge PTSD and depression symptoms.

Franco, M. M., et al. (2021). "Pelvic Floor Muscle Training Effect in Sexual Function in Postmenopausal Women: A Randomized Controlled Trial." The Journal of Sexual Medicine 18(7): 1236-1244.
	BACKGROUND: The prevalence of sexual dysfunction is high in postmenopausal women and pelvic floor muscle training (PFMT) could improve sexual function during this period. AIM: To assess the effect of a PFMT protocol on sexual function in postmenopausal women and to investigate the effect of this protocol on pelvic floor muscle function. METHODS: This is an assessor blinded randomized controlled trial including 77 postmenopausal women. The study was registered in ReBEC Trial: RBR-3s3ff7. The intervention group (n = 40) received an intensive supervised PFMT protocol during 12 weeks and the control group (n = 37) received no intervention. OUTCOMES: The primary outcome of the study was assessed by the Female Sexual Function Index (FSFI) questionnaire and the secondary outcome was the evaluation of pelvic floor muscle function performed by digital palpation using the modified Oxford scale at baseline and after 12 weeks. RESULTS: No difference between groups was found in the FSFI domains and total score at baseline and in the second evaluation after 12 weeks. However, after 12 weeks, a higher percentage of women without sexual dysfunction was found in the intervention group (95% CI = 27.97-72.03) when compared to the control group (95% CI = 7.13-92.87). No difference was found between groups in relation to the pelvic floor muscle function at the baseline (P = .2) and after 12 weeks (P = .06). CLINICAL IMPLICATIONS: PFMT is a conservative intervention that can lead women to have less sexual dysfunction. STRENGTHS & LIMITATIONS: The protocol provided a reduced number of women with sexual dysfunction, the strength of this research is the study design and the limitation is to have used only one tool to assess sexual function although it is a validated questionnaire. CONCLUSION: PFMT decreases sexual dysfunction in postmenopausal women. MM Franco, CC Pena, LM de Freitas, et al. Pelvic Floor Muscle Training Effect in Sexual Function in Postmenopausal Women: A Randomized Controlled Trial. J Sex Med 2021;18:1236-1244.

François, R. and O. D (2021). "Effectiveness of Osteopathic Treatment in Patients With Primary Dysmenorrhea." ClinicalTrials.gov.
	It will be a prospective study, a double-blind randomized controlled clinical trial. The sample group will include 60 patients, between 18 and 30 years old divided into two experimental groups. The experimental group (n = 30) will be treated following an osteopathic treatment, through a bilateral global pelvic manupulation (GPM) and a specific internal technique for mobility of the cervix, and the control group (n = 30) will only carry out a bilateral GPM. A measurement will be made before the first treatment, another after each session, and the last one two weeks after the last intervention (anthropometric measurements, quality of life questionnaire, sexual health, osteopathic tests, pressure point with algometer, pain and medicines consumption). The established outcome measures are: pain intensity according to the visual analog scale (VAS), depression points measured with an algometer, a health-related quality of life questionnaire, questionnaire sexual health and sexual dysfunctions, and the measurement of drug consumption.

Franik, S., et al. (2020). "Aromatase inhibitors for ovarian stimulation in subfertile women with polycystic ovary syndrome: Summary of a Cochrane meta-analysis." Gynakologe 53(12): 841-846.
	Background: Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea), often leading to subfertlity. The aim of this meta-analysis was to compare the effectiveness and safety of aromatase inhibitors with other medical therapies for ovulation induction in subfertile women with PCOS. Method(s): An extensive systematic literature search was done to identify relevant randomized controlled trials (RCTs). The primary outcomes were live birth and ovarian hyperstimulation syndrome (OHSS). Secondary endpoints were pregnancy rate, miscarriage rate, and multiple pregnancy rate. Result(s): A total of 42 RCTs (7935 women) in which the aromatase inhibitor letrozole was used were included. In 25 RCTs, comparisons were also made to clomiphene citrate. Live birth rates were higher with letrozole compared to clomiphene citrate (odds ratio [OR] 1.68, 95% CI 1.42-1.99; 2954 participants; 13 studies; I2= 0%; number needed to treat for an additional beneficial outcome [NNTB]= 10; moderate-quality evidence). There is high-quality evidence that OHSS rates are similar with letrozole and clomiphene citrate (0.5% in both arms: risk difference [RD] -0.00, 95% CI -0.01 to 0.00; 2536 participants; 12 studies; I2= 0%; high-quality evidence). There is evidence for a higher pregnancy rate in favor of letrozole (OR 1.56, 95% CI 1.37-1.78; 4629 participants; 25 studies; I2= 1%; NNTB= 10; moderate-quality evidence). There is little or no difference between treatment groups in the rate of miscarriage (OR 0.94, 95% CI 0.70-1.26; 1210 participants; 18 studies; I2= 0%; high-quality evidence) and multiple pregnancy rate (OR 0.69, 95% CI 0.41-1.16; 3579 participants; 17 studies; I2= 0%; high-quality evidence). Conclusion(s): Compared to clomiphene citrate, letrozole shows a significantly increased rate of live births and pregnancies. The quality of evidence of the analysis is high to moderate. The incidence of OHSS was the same in both groups-Copyright © 2020, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Frankel, J., et al. (2022). "Interpretation of the Meaningfulness of Symptom Reduction with Vibegron in Patients with Overactive Bladder: Analyses from EMPOWUR." Advances in Therapy 39(2): 959-970.
	Introduction: Reductions in bothersome symptoms of overactive bladder (OAB) demonstrate improvement in clinical trials, but patient perception of meaningfulness of such improvement is lacking. In the 12-week phase 3 EMPOWUR trial, vibegron significantly reduced average daily number of micturitions, urgency episodes, and urge urinary incontinence (UUI) episodes vs placebo (P < 0.01 each). This analysis assessed meaningfulness of reductions in clinical endpoints observed in EMPOWUR using patient perception of improvement. Method(s): An anchor-based approach using Patient Global Impression of Change (PGI-C) applied to phase 2 data allowed predefining phase 3 responder definitions. To confirm in phase 3, median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and UUI episodes was generated for each PGI-C category and pooled across treatments. Based on predefined meaningful responder definitions, percentages of patients achieving >= 15% reduction in micturitions (post hoc), >= 50% reduction in urgency episodes (predefined), and >= 75% (predefined) and >= 90% (post hoc) reduction in UUI episodes were determined for patients receiving vibegron or placebo. Result(s): Across treatments, for micturitions, urgency episodes, and UUI episodes, median change from baseline to week 12 increased with greater subjective improvement based on PGI-C scores, and median reductions pooled across treatment groups were higher than the responder definitions that patients perceived as improved. Significantly more patients receiving vibegron vs placebo achieved >= 15% reduction in micturitions (56.3% vs 44.6%, respectively), >= 50% reduction in urgency episodes (39.5% vs 32.8%), >= 75% reduction in UUI episodes (49.3% vs 32.8%), and >= 90% reduction in UUI episodes (35.2% vs 23.5%) at week 12 (P < 0.05 each). Conclusion(s): Significantly more patients treated with vibegron vs placebo in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and UUI episodes that were associated with patient-perceived improvement. Results of these analyses support the meaningfulness of reductions in clinical endpoints observed in the 12-week EMPOWUR trial. Clinical Trials Registration: ClinicalTrials.gov identifier, NCT03492281.Copyright © 2021, The Author(s).

Frankel, J., et al. (2022). "LONG-TERM EFFICACY AND SAFETY OF VIBEGRON FOR OVERACTIVE BLADDER IN PATIENTS 65 YEARS OLD: ANALYSIS FROM THE EMPOWUR EXTENSION TRIAL." Journal of urology 207(SUPPL 5): e649-e650.
	INTRODUCTION AND OBJECTIVE: Overactive bladder (OAB) prevalence increases with age. Vibegron is a b3-adrenergic agonist approved for adults with OAB. In the phase 3 EMPOWUR extension trial, once-daily vibegron 75 mg showed long-term safety and efficacy in patients with OAB, consistent with results of the 12-week study. These post hoc analyses of the extension trial assessed safety and efficacy in patients >=65 years old. METHOD(S): Patients completing EMPOWUR could enter the 40-week extension (NCT03583372). Patients previously receiving vibegron or tolterodine 4 mg extended release continued treatment; patients receiving placebo were randomized 1:1 to vibegron or tolterodine. The primary outcome was safety, assessed by adverse events (AEs). Key efficacy endpoints were change from EMPOWUR baseline at week 52 in average daily micturitions, urge urinary incontinence (UUI) episodes, and urgency episodes. Outcomes were assessed in patients >=65 years old. RESULT(S): Of 505 patients receiving >=1 dose in the extension (n=273, vibegron; n=232, tolterodine), 235 were >=65 years old. Of patients >=65 years old, 71.1% were female; 75.7% had OAB wet (incontinence). After 40-52 weeks of treatment, treatment-related AE rate was similar between vibegron (33.3%) and tolterodine (25.5%) (Table 1). The most commonly occurring AEs (vibegron/tolterodine) were hypertension (10.9%/9.4%), urinary tract infection (7.8%/12.3%), and headache (7.0%/4.7%). Patients who received 52 weeks of active treatment showed improvement in least squares mean change from baseline at week 52 in micturitions (vibegron, -2.3; tolterodine, -1.7), UUI episodes (-1.8; -1.2), and urgency episodes (-3.3; -2.4) (Table 2). Safety and efficacy outcomes were generally similar in patients >=75 years old. CONCLUSION(S): In this subgroup analysis of the EMPOWUR extension trial, vibegron was associated with sustained reductions from baseline in micturitions, UUI episodes, and urgency episodes and was safe in older adults (>=65 y) with OAB, consistent with the overall population.

Frankel, J., et al. (2021). "Vibegron improves quality-of-life measures in patients with overactive bladder: patient-reported outcomes from the EMPOWUR study." International Journal of Clinical Practice 75(5): e13937.
	Background: Quality of life (QOL) can be significantly impacted by symptoms of overactive bladder (OAB). Vibegron is a highly selective β3‐adrenergic receptor agonist that showed efficacy in treatment of symptoms of OAB in the randomised, double‐blind, placebo‐ and active‐controlled phase 3 EMPOWUR trial. Here we report patient‐reported QOL outcomes from the EMPOWUR trial. Methods: Patients were randomly assigned 5:5:4 to receive vibegron 75 mg, placebo or tolterodine 4 mg extended release, respectively, for 12 weeks. Patients completed the OAB questionnaire (OAB‐q) at baseline and at week 12 and the patient global impression (PGI) scales for severity, control, frequency and leakage at baseline and at weeks 4, 8 and 12. Change from baseline at week 12 and responder rates (OAB‐q: patients achieving a ≥10‐point improvement; PGI: patients reporting best possible response) were assessed. Vibegron was compared with placebo, and no comparisons were made between vibegron and tolterodine. Results: Of the 1518 patients randomised, 1463 (placebo, n = 520; vibegron, n = 526; tolterodine, n = 417) had evaluable data for efficacy measures and were included in the analysis. Mean baseline OAB‐q and PGI scores were comparable among treatment groups. At week 12, patients receiving vibegron had greater improvements from baseline in OAB‐q subscores of coping, concern, sleep, health‐related QOL total and symptom bother (P <.01 each) compared with patients receiving placebo; a greater proportion of patients receiving vibegron vs placebo were responders in the OAB‐q coping (P <.05) and symptom bother scores (P <.0001). Compared with placebo, a greater proportion of patients who received vibegron achieved the best response on all PGI end‐points at week 12 (P <.05 each) and were classified as responders (P <.05 each). Conclusions: In the 12‐week EMPOWUR trial, treatment with vibegron was associated with significantly greater and clinically meaningful improvement in OAB‐q and PGI scores compared with placebo, consistent with improvements in OAB symptoms. Clinical trial registration: ClinicalTrials.gov identifier number NCT03492281.

Fransen, A. F., et al. (2020). "Multi-professional simulation-based team training in obstetric emergencies for improving patient outcomes and trainees' performance." The Cochrane Database of Systematic Reviews 12(12): CD011545.
	BACKGROUND: Simulation-based obstetric team training focuses on building a system that will anticipate errors, improve patient outcomes and the performance of clinical care teams. Simulation-based obstetric team training has been proposed as a tool to improve the overall outcome of obstetric health care. OBJECTIVES: To assess the effects of simulation-based obstetric team training on patient outcomes, performance of obstetric care teams in practice and educational settings, and trainees' experience. SEARCH METHODS: The Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) were searched (14 April 2020), together with references checking and hand searching the available proceedings of 2 international conferences. SELECTION CRITERIA: We included randomised controlled trials (RCTs) (including cluster-randomised trials) comparing simulation-based obstetric team training with no, or other type of training. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane, to identify articles, assess methodological quality and extract data. Data from three cluster-randomised trials could be used to perform generic inverse variance meta-analyses. The meta-analyses were based on risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We used the GRADE approach to rate the certainty of the evidence. We used Kirkpatrick's model of training evaluation to categorise the outcomes of interest; we chose Level 3 (behavioural change) and Level 4 (patient outcome) to categorise the primary outcomes. MAIN RESULTS: We included eight RCTs, six of which were cluster-randomised trials, involving more than 1000 training participants and more than 200,000 pregnancies/births. Four studies reported on outcome measures on Kirkpatrick level 4 (patient outcome), three studies on Kirkpatrick level 3 (performance in practice), two studies on Kitkpatrick level 2 (performance in educational settings), and none on Kirkpatrick level 1 (trainees' experience). The included studies were from Mexico, the Netherlands, the UK and the USA, all middle- and high-income countries. Kirkpatrick level 4 (patient outcome) Simulation-based obstetric team training may make little or no difference for composite outcomes of maternal and/or perinatal adverse events compared with no training (3 studies; n = 28,731, low-certainty evidence, data not pooled due to different composite outcome definitions). We are uncertain whether simulation-based obstetric team training affects maternal mortality compared with no training (2 studies; 79,246 women; very low-certainty evidence). However, it may reduce neonatal mortality (RR 0.70, 95% CI 0.48 to 1.01; 2 studies, 79,246 pregnancies/births, low-certainty evidence). Simulation-based obstetric team training may have little to no effect on low Apgar score compared with no training (RR 0.99, 95% 0.85 to 1.15; 2 studies; 115,171 infants; low-certainty evidence), but it probably reduces trauma after shoulder dystocia (RR 0.50, 95% CI 0.25 to 0.99; 1 study; moderate-certainty evidence) and probably slightly reduces the number of caesarean deliveries (RR 0.79, 95% CI 0.67 to 0.93; 1 study; n = 50,589; moderate-certainty evidence) Kirkpatrick level 3 (performance in practice) We found that simulation-based obstetric team training probably improves the performance of the obstetric teams in practice, compared with no training (3 studies; 2398 obstetric staff members, moderate-certainty evidence, data not pooled due to different outcome definitions). AUTHORS' CONCLUSIONS: Simulation-based obstetric team training may help to improve team performance of obstetric teams, and it might contribute to improvement of specific maternal and perinatal outcomes, compared with no training. However, high-certainty evidence is lacking due to serious risk of bias and imprecision, and the effect cannot be generalised for all outcomes. Future studies investigating simulation-based obstetric team training compared training courses with a different instructional design should carefully consider how and when to measure outcomes. Particular attention should be paid to effect measurement at the level of patient outcome, taking into consideration the low incidence of adverse maternal and perinatal events.

Frassanito, L., et al. (2023). "Hypotension Prediction Index guided Goal Directed therapy and the amount of Hypotension during Major Gynaecologic Oncologic Surgery: a Randomized Controlled clinical Trial." Journal of Clinical Monitoring and Computing 37(4): 1081-1093.
	Intraoperative hypotension (IOH) is associated with increased morbidity and mortality. Hypotension Prediction Index (HPI) is a machine learning derived algorithm that predicts IOH shortly before it occurs. We tested the hypothesis that the application of the HPI in combination with a pre-defined Goal Directed Therapy (GDT) hemodynamic protocol reduces IOH during major gynaecologic oncologic surgery. We enrolled women scheduled for major gynaecologic oncologic surgery under general anesthesia with invasive arterial pressure monitoring. Patients were randomized to a GDT protocol aimed at optimizing stroke volume index (SVI) or hemodynamic management based on HPI guidance in addition to GDT. The primary outcome was the amount of IOH, defined as the timeweighted average (TWA) mean arterial pressure (MAP) < 65 mmHg. Secondary outcome was the TWA-MAP < 65 mmHg during the first 20 min after induction of GA. After exclusion of 10 patients the final analysis included 60 patients (30 in each group). The median (25-75th IQR) TWA-MAP < 65 mmHg was 0.14 (0.04-0.66) mmHg in HPI group versus 0.77 (0.36-1.30) mmHg in Control group, P < 0.001. During the first 20 min after induction of GA, the median TWA-MAP < 65 mmHg was 0.53 (0.06-1.8) mmHg in the HPI group and 2.15 (0.65-4.2) mmHg in the Control group, P = 0.001. Compared to a GDT protocol aimed to SVI optimization, a machine learning-derived algorithm for prediction of IOH combined with a GDT hemodynamic protocol, reduced IOH and hypotension after induction of general anesthesia in patients undergoing major gynaecologic oncologic surgery. Trial registration number: NCT04547491. Date of registration: 10/09/2020.Copyright © 2023, The Author(s).

Frassanito, L., et al. (2023). "Effect of a pre-emptive 2-hour session of high-flow nasal oxygen on postoperative oxygenation after major gynaecologic surgery: a randomised clinical trial." British Journal of Anaesthesia 131(4): 775-785.
	Background: We aimed at determining whether a 2-h session of high-flow nasal oxygen (HFNO) immediately after extubation improves oxygen exchange after major gynaecological surgery in the Trendelenburg position in adult female patients. Method(s): In this single-centre, open-label, randomised trial, patients who underwent major gynaecological surgery were randomised to HFNO or conventional oxygen treatment with a Venturi mask. The primary outcome was the Pao2/FiO2 ratio after 2 h of treatment. Secondary outcomes included lung ultrasound score, diaphragm thickening fraction, dyspnoea, ventilatory frequency, Paco2, the percentage of patients with impaired gas exchange (Pao2/FiO2 <=40 kPa) after 2 h of treatment, and postoperative pulmonary complications at 30 days. Result(s): A total of 83 patients were included (42 in the HFNO group and 41 in the conventional treatment group). After 2 h of treatment, median (inter-quartile range) Pao2/FiO2 was 52.9 (47.9-65.2) kPa in the HFNO group and 45.7 (36.4 -55.9) kPa in the conventional treatment group (mean difference 8.7 kPa [95% CI: 3.4 to 13.9], P=0.003). The lung ultrasound score was lower in the HFNO group than in the conventional treatment group (9 [6-10] vs 12 [10-14], P<0.001), mostly because of the difference of the score in dorsal areas (7 [6-8] vs 10 [9-10], P<0.001). The percentage of patients with impaired gas exchange was lower in the HFNO group than in the conventional treatment group (5% vs 37%, P<0.001). All other secondary outcomes were not different between groups. Conclusion(s): In patients who underwent major gynaecological surgery, a pre-emptive 2-h session of HFNO after extubation improved postoperative oxygen exchange and reduced atelectasis compared with a conventional oxygen treatment strategy. Clinical trial registration: NCT04566419.Copyright © 2023 British Journal of Anaesthesia

Frazer, K., et al. (2022). "Systematic Review of Smoking Cessation Interventions for Smokers Diagnosed with Cancer." International Journal of Environmental Research and Public Health 19(24).
	The detrimental impact of smoking on health and wellbeing are irrefutable. Additionally, smoking is associated with the development of cancer, a reduction treatment outcomes and poorer health outcomes. Nevertheless, a significant number of people continue to smoke following a cancer diagnosis. Little is understood of the smoking cessation services provided to smokers with cancer or their engagement with them. This systematic review aimed to identify existing smoking cessation interventions for this cohort diagnosed with breast, head and neck, lung and cervical cancers (linked to risk). Systematic searches of Pubmed, Embase, Psych Info and CINAHL from 1 January 2015 to 15 December 2020 were conducted. Included studies examined the characteristics of smoking cessation interventions and impact on referrals and quit attempts. The impact on healthcare professionals was included if reported. Included studies were restricted to adults with a cancer diagnosis and published in English. No restriction was placed on study designs, and narrative data synthesis was conducted due to heterogeneity. A review protocol was registered on PROSPERO CRD 42020214204, and reporting adheres to PRISMA reporting guidelines. Data were screened, extracted in duplicate and an assessment of the quality of evidence undertaken using Mixed Methods Assessment Tool. 23 studies met the inclusion criteria, representing USA, Canada, England, Lebanon, Australia and including randomized controlled trials (9), observational studies (10), quality improvement (3), and one qualitative study. Hospital and cancer clinics [including a dental clinic] were the settings for all studies. 43% (10/23) of studies reported interventions for smokers diagnosed with head and neck cancer, 13% (3/23) for smokers diagnosed with lung cancer, one study provides evidence for breast cancer, and the remaining nine studies (39%) report on multiple cancers including the ones specified in this review. Methodological quality was variable. There were limited data to identify one optimal intervention for this cohort. Key elements included the timing and frequency of quit conversations, use of electronic records, pharmacotherapy including extended use of varenicline, increased counselling sessions and a service embedded in oncology departments. More studies are required to ensure tailored smoking cessation pathways are co-developed for smokers with a diagnosis of cancer to support this population.

Frechtling, D., et al. (2024). "The Association Between Human Immunodeficiency Virus and Bacterial Vaginosis and Metronidazole Treatment Failure for Trichomonas vaginalis." Sexually Transmitted Diseases 51(1): 61-64.
	Background Trichomonas vaginalis (TV) is a common sexually transmitted infection. High rates of repeated infections have been observed, particularly among women living with human immunodeficiency virus (HIV). Trichomonas vaginalis frequently cooccurs with bacterial vaginosis (BV). The purpose of this study was to determine if coinfections with TV, BV, and HIV could lead to differential treatment failure outcomes. Methods Data were pooled from 2 prior randomized control trials comparing 2 g oral single-dose versus 500-mg twice daily oral 7-day dose metronidazole for the treatment of TV in HIV infected and HIV uninfected women. Trichomonas vaginalis rates 1-month postcompletion of treatment were compared by arm, HIV and BV status after removing those who had sexual reexposure, and/or did not complete their treatment. Results Data for 795 subjects were included in the study, of which 76 (9.6%) experienced treatment failure. In the final multivariable model, which included treatment dose, HIV status, and BV status, odds of treatment failure infection in the 7-day dose group were lower than the odds in the single dose group (odds ratio, 040; 95% confidence interval, 0.23-0.68). Treatment failure was lower in the multidose arm compared with single dose for both HIV-infected (4.0% vs 10.3%; P = 0.0568) and HIV-uninfected (7.3% vs 15.4%; P = 0.0037). Neither HIV nor BV was associated with higher treatment failure. Conclusions Human immunodeficiency virus infection and BV status did not significantly alter the rate of repeat infection for either single dose or 7-day dose metronidazole. Among all women, 7-day metronidazole lowered the odds of treatment failure.Copyright © Lippincott Williams & Wilkins.

Frederice Claudia, P., et al. (2022). "Effect of Vaginal Stretching and Photobiomodulation Therapy on Sexual Function in Women With Pelvic Floor Myofascial Pain - A Randomized Clinical Trial." The Journal of Sexual Medicine 19(1): 98-105.
	Background: Spasm or increased tonus of the pelvic floor muscles (PFM) can cause myofascial pain (MP), which may result in painful intercourse and sexual dysfunction.; Aim: The effect of vaginal stretching (VS) with photobiomodulation therapy (PBMT) is compared to VS with sham PBMT in overall sexual function, rate and severity of painful intercourse at baseline and after treatment in women with pelvic floor MP.; Methods: A double-blind randomized clinical trial of 103 women with MP: 1 group received 10 sessions of VS with PBMT (4 Joules of near-infrared light-808 nm at 3 points), and the other group received VS with sham PBMT.; Outcomes: Impact of treatment was measured by the number of women experiencing painful intercourse, Pain severity was measured by Visual Analog Scale and sexual function was assessed by the FSFI questionnaire. Variables were assessed at baseline and after ten sessions in the intervention groups.; Results: After treatment, the number of women experiencing painful intercourse was significantly lower in both the VS with PBMT group (90.2-55%, P = .001), and VS with sham PBMT group (86.6-46.2%, P < .001). There was a significant reduction in pain measure by Visual Analog Scale (P < .001, [VS with PBMT group: P = .002; VS with sham PBMT group: P < .001]). There was a significant decrease in the number of participants with sexual dysfunction (FSFI score ≤26.55) after the treatment in the VS with PBMT group (92.2-74.5%, P = .003) and in the VS with sham PBMT group (90.4-76.9%, P = .035). Both groups showed improvement in the FSFI pain domain after treatment (P < .001, [VS with PBMT group: P = .038; VS with sham PBMT group: P = .005]). Only the VS with sham PBMT group had a significant increase in FSFI desire and total score (P < .001) after treatment.; Clinical Implications: We found that VS associated or not with PBMT may be effective in reducing complaints of painful intercourse, alleviating pain severity, and reducing the number of women with pelvic floor MP suffering from sexual dysfunction.; Strengths & Limitations: Strengths of this study are the randomized design and use of validated questionnaires. Limitation of the study is the lack of a long follow-up period and the lack of a usual care comparison group hampers generalizability of the results.; Conclusion: VS only and VS with PBMT have short-term efficacy in reducing painful intercourse and reducing a number of women with sexual dysfunction. Frederice CP, de Mira TAA, Machado HC, et al. Effect of Vaginal Stretching and Photobiomodulation Therapy on Sexual Function in Women With Pelvic Floor Myofascial Pain - A Randomized Clinical Trial. J Sex Med 2022;19:98-105. (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Frederick, R. U., et al. (2021). Comparison of Nodal Staging in Endometrial Cancer.
	No Results Available Procedure: Sentinel node procedure|Procedure: Selective staging Recurrence-free survival rate|Progression-free survival rate|Disease-specific survival rate|Overall patient survival rate|Concordance of SELECTIVE and SENTINEL NODE surgical staging with final pathology|Patient morbidity|Patient mortality Female Phase 3 38 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MCC-21-GYN-210 June 13, 2023

Free, L. L., et al. (2024). "Effects of aromatherapy on patient satisfaction with procedural abortion at less than 10 weeks' gestation: A randomized controlled trial." Contraception 130: 110311.
	Objectives: This study aimed to compare satisfaction with procedural abortion prior to 10 weeks' gestation in patients randomized to lavender essential oil aromatherapy vs placebo (jojoba oil). Study design: This randomized trial compared lavender aromatherapy vs placebo in patients undergoing procedural abortion <10 weeks' gestation. Participants self-administered and inhaled oil during their procedures. Our primary outcome was composite mean score on the Iowa Satisfaction with Anesthesia Scale. Participants completed the State-Trait Anxiety Inventory, a visual analog scale reporting maximum procedural pain, and reported postprocedure aromatherapy acceptability. Result(s): We analyzed 112 participants randomized to aromatherapy (n = 57) vs placebo (n = 55). Baseline characteristics were similar between groups. We found no difference in overall satisfaction (mean Iowa Satisfaction with Anesthesia Scale scores aromatherapy: 0.72 +/- 0.96 vs placebo: 0.46 +/- 0.98, p = 0.17) or maximum procedural pain (median visual analog scale score aromatherapy: 65 [range: 4-95] vs placebo: 63 [range: 7-97], p = 0.91). Independent predictors of satisfaction included the use of oral sedation (B: 0.36; 95% CI: 0.04-0.69), state anxiety (B: -0.45; 95% CI: -0.79 to -0.10), and maximum procedural pain (B: -0.17; 95% CI: -0.25 to -0.09). The aromatherapy participants were significantly more likely to have found inhaling scented oil helpful during their procedure (71.9% vs 45.5%; p = 0.005) and would recommend it to a friend who needed a procedural abortion (86.0% vs 56.4%; p = 0.0005) compared to those in the placebo group. Additionally, patients in the aromatherapy group were significantly more likely to agree with the statement, "If I need another procedural abortion, I would want to inhale scented oil during my procedure" (87.7% vs 70.9%; p = 0.03). Conclusion(s): The adjunctive use of lavender aromatherapy during first-trimester procedural abortion does not improve satisfaction with anesthesia but is highly valued by patients. Implications: Oral opioids as an adjunct to standard analgesics during procedural abortion (ibuprofen and paracervical block) do not decrease pain, and nonopioid options are lacking. Given current limited anesthesia options, aromatherapy could serve as an affordable and acceptable nonopioid adjunct to current standard of care during procedural abortion. ClinicalTrials.gov Identifier: NCT04969900.Copyright © 2023 Elsevier Inc.

Frenel, J. S., et al. (2022). "Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial." Annals of oncology : official journal of the European Society for Medical Oncology 33(10): 1021-1028.
	Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown.; Patients and Methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death.; Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90).; Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.; Competing Interests: Disclosure JSF reports personal fees from Roche Genentech, personal fees and non-financial support from Seattle Genetics, Novartis, Pfizer, Lilly, Novartis, GSK, Clovis oncology, AstraZeneca, Daiichi Sankyo, Gilead, MSD, Pierre Fabre, and Amgen, outside the submitted work. PP reports non-financial support from GSK, AstraZeneca, Clovis Oncology outside the submitted work. JAL reports personal fees from Pfizer, AstraZeneca, GSK, MSD, Clovis Oncology, Eisai, Bristol Myers Squibb, Artios Pharma, VBL Therapeutics, Neopharm, outside the submitted work. RTP reports personal fees from AbbVie, AstraZeneca, Eisai, Genentech / Roche, GSK Inc., Merck & Co, Sutro Biopharma, Vascular Biogenics Ltd, outside the submitted work. SP reports personal fees from, AstraZeneca, MSD; ROCHE, Clovis, GSK, Pfizer, PharmaMar, outside the submitted work. NC reports personal fees from AstraZeneca, Esai, Genentech, GSK, Merck, Pfizer, Regeneron pharmaceutical, outside the submitted work. TWPS reports personal fee from AstraZeneca, Tesaro, GSK, outside the submitted work. GSS has received grant from Agendia, AstraZeneca, Merck, Novartis, Roche, Seagen, outside the submitted work. CKL reports personal fee from AstraZeneca, Amgen, Takeda, Boehringer Ingelheim, Pfizer, Yuhan, Merck KGA, Roche, MSD, outside the submitted work. EPL reports grants and personal fees from AstraZeneca, Merck, GSK, Roche, Incyte, ARCAGY Research, outside the submitted work. All other authors have declared no conflicts of interest. (Copyright © 2022. Published by Elsevier Ltd.)

Freuding, M., et al. (2019). "Mistletoe in oncological treatment: a systematic review : Part 2: quality of life and toxicity of cancer treatment." Journal of Cancer Research and Clinical Oncology 145(4): 927-939.
	Purpose: One important goal of any cancer therapy is to improve or maintain quality of life. In this context, mistletoe treatment is discussed to be highly controversial. The aim of this systematic review is to give an extensive overview about the current state of evidence concerning mistletoe therapy of oncologic patients regarding quality of life and side effects of cancer treatments.; Methods: In September and October 2017, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and "Science Citation Index Expanded" (Web of Science) were systematically searched.; Results: The search strategy identified 3647 articles and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Regarding quality of life, 17 publications reported results. Studies with better methodological quality show less or no effects on quality of life.; Conclusions: With respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

Freuding, M., et al. (2019). "Mistletoe in oncological treatment: a systematic review : Part 1: survival and safety." Journal of Cancer Research and Clinical Oncology 145(3): 695-707.
	Purpose: Mistletoe treatment of cancer patients is discussed highly controversial in the scientific literature. Aim of this systematic review is to give an extensive overview about current state of research concerning mistletoe therapy of oncologic patients regarding survival, quality of life and safety.; Methods: In September and October 2017 Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and "Science Citation Index Expanded" (Web of Science) were systematically searched.; Results: The search strategy identified 3647 hits and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Patient relevant endpoints were overall survival (14 studies, n = 1054), progression- or disease-free survival or tumor response (10 studies, n = 1091). Most studies did not show any effect of mistletoe on survival. Especially high quality studies do not show any benefit.; Conclusions: With respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

Freuding, M., et al. (2019). "Mistletoe in oncological treatment: a systematic review : Part 1: survival and safety." Journal of Cancer Research and Clinical Oncology 145(3): 695-707.
	PURPOSE: Mistletoe treatment of cancer patients is discussed highly controversial in the scientific literature. Aim of this systematic review is to give an extensive overview about current state of research concerning mistletoe therapy of oncologic patients regarding survival, quality of life and safety. METHODS: In September and October 2017 Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and "Science Citation Index Expanded" (Web of Science) were systematically searched. RESULTS: The search strategy identified 3647 hits and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Patient relevant endpoints were overall survival (14 studies, n = 1054), progression- or disease-free survival or tumor response (10 studies, n = 1091). Most studies did not show any effect of mistletoe on survival. Especially high quality studies do not show any benefit. CONCLUSIONS: With respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

Freyer, G., et al. (2023). "BEVACIZUMAB, OLAPARIB and DURVALUMAB in PATIENTS with RELAPSED OVARIAN CANCER (THE GINECO BOLD STUDY): PROGNOSTIC VALUE of KELIM-B and NANOSTRING TUMOR INFLAMMATION SIGNATURE." Anticancer Research 43(7): 3368-3369.
	Background/Aim: Strategies combining bevacizumab, olaparib, and durvalumab are anticipated to have synergistic activity. We evaluated this triple combination in platinumresistant and platinum-sensitive relapse of advanced ovarian cancer. Patients and Methods: This open-label, multicenter phase 2 study assessed activity and safety of 1120 mg durvalumab once every 3 weeks (q3w), 15 mg/kg bevacizumab q3w, and 300 mg tolaparib twice daily, in patients with relapsed, high-grade epithelial, advanced ovarian cancer. Previous bevacizumab or poly (ADP-ribose) polymerase inhibitor was permitted. The primary endpoint was the rate of non-progression at 3 months for patients with platinum-resistant relapse or 6 months for those with platinum-sensitive relapse. Secondary endpoints included the modeled cancer antigen 125 (CA-125) elimination rate constant (KELIM-B) for longitudinal CA-125 kinetics over 100 days, and the Nanostring tumor inflammation signature at baseline. Result(s): Between March 2019 and January 2020, 74 patients were included (41 with platinum-resistant and 33 with platinum-sensitive disease). With a median follow-up of 15.4 months, non-progression rates were 69.8% [90% confidence interval (CI)=55.9-80.0%] at 3 months for those with platinum-resistant relapse, and 43.8% (90% CI=29.0- 57.4%) at 6 months for those with platinum-sensitive relapse. Median PFS was 4.1 months (95% CI=3.5-5.9 months) for those with platinum-resistant relapse and 4.9 months (95% CI=2.9-7.0 months) for those with platinum-sensitive relapse. Median overall survival was 18.8 months (95% CI=9.6 months-not reached) and 18.5 months (95% CI=15.6 months-not reached), respectively. Higher (favorable) KELIM-B values were prognostic for improved PFS [median=6.2 months (95% CI=3.5-9.0 months) vs. 1.5 months (95% CI=0.7-6.2 months); p=0.03]. A higher tumor inflammation signature was associated with longer median PFS, notably for patients with platinum-sensitive relapse [6.9 months (95% CI=3.3-10.3) vs. 4.0 months (95% CI=1.4-5.7 months)]. No toxic deaths or major safety signals were observed. Conclusion(s): The chemotherapy-free triple combination of durvalumab, olaparib and bevacizumab was well tolerated, with encouraging efficacy in heavily pretreated patients with platinum-resistant relapse. Favorable KELIM-B and higher immune-related biomarkers are prognostic for survival. Further investigation of the triple combination is warranted.

Fricová, L. and J. Sláma (2022). "Current knowledge on fertility-sparing treatment of cervical cancer patients [Czech]." Ceska gynekologie 87(5): 362-370.
	Introduction: Cervical cancer directly affects the reproductive function of women of childbearing age. Up to one-third of the disease is dia-gnosed in women younger than 45 years of age, who may still have open reproductive plans. Therefore, in recent years, there has been increasing interest in performing fertility-sparing treatment (FST), which aims to preserve fertility while achieving the same oncologic safety as radical surgical treatment.; Objective: To summarize the current knowledge on FST in women with early stages of cervical cancer.; Methods: Review of published literature on the topic using medical databases.; Results: FST is reserved for patients with HPV-associated cervical cancer up to stage IB with negative nodes. Conservative procedures (conization and simple vaginal trachelectomy) and radical trachelectomy are available. Conservative procedures for tumors 2cm have comparable oncological outcomes as radical treatment with a significantly lower rate of perinatological complications. On average, 55% of patients become pregnant after treatment and of these, on average 70% give birth to a live newborn. Approximately 38% of deliveries are preterm, most often after radical trachelectomy. The most common postoperative complication with direct impact on fertility is cervical stenosis.; Conclusion: In a selected group of patients with tumors up to 2cm, FST is a safe procedure with good perinatological outcomes. However, it remains unclear whether it is safe to offer this treatment to patients with larger tumors. The use of neoadjuvant chemotherapy followed by conservative surgery is a promising approach but requires further validation in clinical trials.

Friedenreich, C. M., et al. (2020). "Physical Activity and Mortality in Cancer Survivors: A Systematic Review and Meta-Analysis." JNCI Cancer Spectrum 4(1): pkz080.
	BACKGROUND: Recommendations for improved survival after cancer through physical activity (PA) exist, although the evidence is still emerging. Our primary objective was to conduct a systematic review and meta-analysis of the association between prediagnosis and postdiagnosis PA and survival (cancer-specific, all-cause, and cardiovascular disease mortality) for all cancers and by tumor site. Secondary objectives were to examine the associations within population subgroups, by PA domain, and to determine the optimal dose of PA related to survival. METHODS: PubMed, EMBASE, and SportsDiscus databases were searched from inception to November 1, 2018. DerSimonian-Laird random-effects models were used to estimate the summary hazard ratios (HRs) and 95% confidence intervals (CI) for primary and secondary analyses and to conduct dose-response analyses. RESULTS: Evidence from 136 studies showed improved survival outcomes with highest vs lowest levels of prediagnosis or postdiagnosis total or recreational PA for all-cancers combined (cancer specific mortality: HR = 0.82, 95% CI = 0.79 to 0.86, and HR = 0.63, 95% CI = 0.53 to 0.75, respectively) as well as for 11 specific cancer sites. For breast and colorectal cancers, greater reductions were observed for postdiagnosis PA (HR = 0.58-0.63) compared with prediagnosis PA (HR = 0.80-0.86) for cancer-specific and all-cause mortality. Survival benefits through PA were observed in most subgroups (within sex, body mass index, menopausal status, colorectal subtypes, and PA domain) examined. Inverse dose-response relationships between PA and breast cancer-specific and all-cause mortality were observed, with steep reductions in hazards to 10-15 metabolic equivalent hours per week. CONCLUSION: Higher prediagnosis and postdiagnosis levels of PA were associated with improved survival outcomes for at least 11 cancer types, providing support for global promotion of PA guidelines following cancer.

Frieder, A., et al. (2019). "Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development." CNS drugs 33(3): 265-282.
	Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cognitive, behavioral, and emotional development with lasting consequences. There are a number of therapeutic interventions for postpartum depression including pharmacotherapy, psychotherapy, neuromodulation, and hormonal therapy among others, most of which have been adapted from the treatment of major depressive disorder outside of the peripartum period. Current evidence of antidepressant treatment for postpartum depression is limited by the small number of randomized clinical trials, underpowered samples, and the lack of long-term follow-up. The peripartum period is characterized by rapid and significant physiological change in plasma levels of endocrine hormones, peptides, and neuroactive steroids. Evidence supporting the role of neuroactive steroids and gamma-aminobutyric acid (GABA) in the pathophysiology of postpartum depression led to the investigation of synthetic neuroactive steroids and their analogs as potential treatment for postpartum depression. Brexanolone, a soluble proprietary intravenous preparation of synthetic allopregnanolone, has been developed. A recent series of open-label and placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has led to the submission for regulatory approval to the US Food and Drug Administration (decision due in March 2019). SAGE-217, an allopregnanolone analog, with oral bioavailability, was recently tested in a randomized, double-blind, placebo-controlled phase III study in severe postpartum depression, with reportedly positive results. Finally, a 3beta-methylated synthetic analog of allopregnanolone, ganaxolone, is being tested in both intravenous and oral forms, in randomized, double-blind, placebo-controlled phase II studies in severe postpartum depression.Copyright © 2019, Springer Nature Switzerland AG.

Friedlander, M., et al. (2021). "Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial." The Lancet. Oncology 22(5): 632‐642.
	BACKGROUND: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression‐free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum‐based chemotherapy. We analysed health‐related quality of life (HRQOL) and patient‐centred outcomes in SOLO1, and the effect of radiological disease progression on health status. METHODS: SOLO1 is a randomised, double‐blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0‐1; had newly diagnosed, advanced, high‐grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum‐based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum‐based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy‐Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality‐adjusted progression‐free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.gov, NCT01844986. INTERPRETATION: The substantial progression‐free survival benefit provided by maintenance olaparib in the newly diagnosed setting was achieved with no detrimental effect on patients' HRQOL and was supported by clinically meaningful quality‐adjusted progression‐free survival and TWiST benefits with maintenance olaparib versus placebo. FUNDING: AstraZeneca and Merck Sharp & Dohme. FINDINGS: Between Sept 3, 2013, and March 6, 2015, 1084 patients were enrolled. 693 patients were ineligible, leaving 391 eligible patients who were randomly assigned to olaparib (n=260) or placebo (n=131; one placebo patient withdrew before receiving any study treatment), with a median duration of follow‐up of 40·7 months (IQR 34·9‐42·9) for olaparib and 41·2 months (32·2‐41·6) for placebo. There was no clinically meaningful change in TOI score at 24 months within or between the olaparib and placebo groups (adjusted mean change in score from baseline over 24 months was 0·30 points [95% CI ‐0·72 to 1·32] in the olaparib group vs 3·30 points [1·84 to 4·76] in the placebo group; between‐group difference of ‐3·00, 95% CI ‐4·78 to ‐1·22; p=0·0010). Mean quality‐adjusted progression‐free survival (olaparib 29·75 months [95% CI 28·20‐31·63] vs placebo 17·58 [15·05‐20·18]; difference 12·17 months [95% CI 9·07‐15·11], p<0·0001) and the mean duration of TWiST (olaparib 33·15 months [95% CI 30·82‐35·49] vs placebo 20·24 months [17·36‐23·11]; difference 12·92 months [95% CI 9·30‐16·54]; p<0·0001) were significantly longer with olaparib than with placebo.

Frigerio, M., et al. (2019). "Long-term effects of episiotomy on urinary incontinence and pelvic organ prolapse: a systematic review." Archives of Gynecology and Obstetrics 299(2): 317-325.
	Purpose: To focus attention on the long-term effects of episiotomy on urinary incontinence and pelvic organ prolapse.; Methods: A systematic review was conducted including only studies with mean follow-up ≥ 5 years. We searched using combinations of the following keywords and text words: "episiotomy", "perineal laceration", "perineal tear", "perineal damage" and "long term", "long term outcomes", "prolapse", "pelvic organ prolapse", "pelvic floor", "pelvic floor dysfunction", "urinary incontinence", "hysterocele", "cystocele" and "rectocele".; Results: The electronic database search provided a total of 6154 results. After exclusions, 24 studies were included yielding the following results: (1) episiotomy might be detrimental with respect to urinary incontinence symptoms; (2) the relationship between episiotomy and anti-incontinence surgery is not clear; (3) episiotomy does not seem to negatively influence genital prolapse development and might even be protective with respect to prolapse severity and prevalence; (4) episiotomy does not seem to affect genital prolapse surgery rate.; Conclusions: We did not find evidence for a long-term beneficial effect of episiotomy in the prevention of urinary incontinence symptoms and anti-incontinence surgery. Episiotomy does not seem to negatively influence genital prolapse development and might even be protective with respect to prolapse severity and prevalence without affecting surgery rates.

Frijstein, M. M., et al. (2023). "Effects of a pre-visit online information tool about genetic counselling for ovarian cancer patients, a randomized controlled trial." Patient Education and Counseling 113: 107786.
	Objective: In the Netherlands, patients with ovarian cancer are offered genetic testing. Pre-test preparation may help counseling patients. The aim of this study was to determine if use of a web-based intervention, leads to more effective genetic counseling of ovarian cancer patients.; Methods: Between 2016 and 2018, 127 ovarian cancer patients referred for genetic counseling in our hospital participated in this trial. 104 Patients were analyzed. All patients filled out questionnaires pre- and post-counseling. The intervention group also completed a questionnaire after visiting an online tool. Length of consultation, patients' satisfaction, knowledge, anxiety, depression and distress were compared before and after counselling.; Results: The intervention group had the same level of knowledge compared to the counseling group, but at an earlier point in time. They were satisfied with the intervention (86%) and better prepared for counseling (66%). The intervention did not lead to shorter consultations. No differences in levels of anxiety, depression, distress and satisfaction were observed.; Conclusion: Although consultation length was unaffected, the improvements in knowledge after online education and patients satisfaction indicates that this tool can be an effective addition to genetic counseling.; Practice Implications: Use of an educational tool may lead to a more effective, personalized way of genetic counselling and enables shared decision making.; Competing Interests: Declaration of Competing Interest None. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Frohlich, G., et al. (2023). "Are active dwell positions always necessary in the ring/ovoids channel of the cervical applicator in the intracavitary-interstitial brachytherapy of cervical cancer?" Journal of Contemporary Brachytherapy 15(1): 48-56.
	Purpose: To compare dosimetric parameters of brachytherapy (BT) treatment plans made with or without active source positions of the ring/ovoid (R/O) applicator in locally advanced cervical cancer patients. Material(s) and Method(s): Sixty patients with cervical cancer without vaginal involvement were selected for the study, who received intra-cavitary/interstitial BT. For each patient, two plans with and without active source dwell positions in R/O were created, using the same dose-volume constraints. EQD2 total doses from external beam and BT of target volumes and organs at risk (OARs) between the competing plans were compared. Result(s): There was no significant difference in the dose of high-risk clinical target volume (HR-CTV) and gross tumor volume (GTV) between the plans with inactive vs. active R/O. The mean D98 of intermediate-risk clinical target volume (IR-CTV) was significantly lower with inactive R/O; however, the GEC-ESTRO (EMBRACE II study) and ABS criteria were fulfilled in 96% in both plans. There was no difference in dose homogeneity, but conformity of the plans with inactive R/O was higher. Doses to all OARs were significantly lower in plans without R/O activation. While all the plans without R/O activation fulfilled the recommended dose criteria for OARs, it was less achievable with R/O activation. Conclusion(s): Inactivation of R/O applicator results in similar dose coverage of the target volumes with lower doses to all OARs, as activation of R/O in cervix cancer patients when HR-CTV does not extend to R/O applicator. The use of active source positions in R/O shows worse performance regarding the fulfilment of the recommended criteria for OARs.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

frtzv, R. B. R. (2022). "Effects of the use of a mobile application in women with complaints of stress urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: 62 participants will be randomly divided into 2 groups: one will perform a pelvic floor muscle training protocol guided by an application and the other, through a booklet. Before and after 6 and 12 weeks of intervention, the volunteers will be evaluated using the King's Health Questionnaire (KHQ) and the International Consultation on Incontinence Questionnaire ‐ Short Form (ICIQ‐SF). At the end of the research, a comparison of urinary complaints, quality of life and satisfaction with the intervention will be carried out between groups (app and booklet) and between phases (pre‐treatment, after 6 weeks, after 12 weeks). Initial assessments will be conducted before participants are randomized (1:1) to two groups (app, booklet), through a computer‐generated list of random numbers (by a single researcher, who will not have access to the data). evaluation or training of participants). Participants will be informed that they will receive one of two different forms of protocol application, but will not be aware of the study hypothesis. Statistical analysis will be performed by another person. L01.224.900.685 CONDITION: C12.050.351.968.934 Urinary incontinence PRIMARY OUTCOME: With this study, it is expected that the use of the application will improve the symptoms of urinary leakage in women, which will be evaluated through the Iciq‐sf (International Consultation on Incontinence Questionnaire ‐ Short Form) and Khq (King's Health Questionnaire). SECONDARY OUTCOME: With this study, it is expected that the use of the application will improve the impact of urinary incontinence on quality of life, which will be evaluated through the Iciq‐sf (International Consultation on Incontinence Questionnaire ‐ Short Form) and Khq (King's Health Questionnaire). INCLUSION CRITERIA: Women with symptoms of stress urinary incontinence and/or mixed; aged over 18; literate; with preserved cognitive ability; with access to the internet; who have a mobile device with Android system; with understanding of the functioning of the application developed by the team of researchers.

Frydman, J. L., et al. (2022). "Racial/ethnic disparities in serious illness communication for patients with cancer." Journal of Clinical Oncology 40(16).
	Background: Racial/ethnic disparities in serious illness communication exist between patients with cancer and their oncologists. Our prior work has shown that goals of care discussions are three minutes shorter with racial/ethnic minority patients. In this study, we sought to compare oncologist's use of serious illness communication skills, patient participatory behavior, and overall communication quality during encounters with patients with advanced cancer of different self‐reported races/ethnicities. Methods: We analyzed baseline recordings from a two‐arm multisite randomized controlled trial to test a coaching model of communication skills training for solid tumor oncologists and their newly diagnosed advanced cancer patients. We audio recorded post‐imaging patient‐oncologist encounters for patients receiving systemic cancer treatment and coded transcripts for oncologist's use of serious illness communication skills (coded as count/encounter): open‐ended questions, reflections, empathic responses to patient empathic opportunities, empathic statements, ���sorry” statements, and elicitation of questions. We also assessed global codes of oncologist communication (assessed on 5‐point Likert scales): flow, concerns addressed, attention, warmth, and respect. Finally, we coded patient participatory behavior (coded as count/encounter): asking questions and assertive responses. We compared the skills and behaviors by race/ethnicity of the patient using the non‐parametric Kruskal‐Wallis test. Results: We included the 56 (38%) recordings with oncologists who did not receive the intervention. The patients in these encounters were 25 (45%) female; 32 (57%) over the age of 65; 23 (41%) White Non‐Hispanic, 20 (36%) Black Non‐Hispanic, and 11 (20%) Hispanic. Overall, oncologists responded empathically to patients' emotions only 19% of the time. Oncologists used fewer reflective statements with Black Non‐Hispanic patients (mean 0.3 statements/encounter) as compared to White Non‐Hispanic patients (1.1) and Hispanic patients (1.1), p = 0.02. Furthermore, coders rated oncologists as being less likely to address concerns of Black Non‐Hispanic patients (mean Likert scale 3.1) as compared to White Non‐Hispanic (3.8) and Hispanic (3.4) patients, p = 0.04. Finally, coders rated oncologists as having less warmth with Black Non‐Hispanic patients (mean Likert scale 2.9) as compared to White Non‐Hispanic (3.8) and Hispanic (3.3) patients, p = 0.04. Conclusions: In this diverse sample of patients with advanced cancer, oncologists used fewer reflective statements, were less attentive to concerns, and expressed less warmth with Black Non‐Hispanic patients. Interventions are needed to overcome these striking racial/ethnic disparities in serious illness communication for patients with cancer.

Fu, H., et al. (2023). "Survival outcomes of robotic-assisted laparoscopy versus conventional laparoscopy and laparotomy for endometrial cancer: A systematic review and meta-analysis." Gynecologic Oncology 174: 55-67.
	Objective: Robotic-assisted laparoscopy (RALS) has gained widespread acceptance in the field of gynecological oncology. However, whether the prognosis of endometrial cancer after RALS is superior to conventional laparoscopy (CLS) and laparotomy (LT) remains inconclusive. Therefore, the aim of this meta-analysis was to compare the long-term survival outcomes of RALS with CLS and LT for endometrial cancer.; Methods: A systematic literature search was conducted on electronic databases (PubMed, Cochrane, EMBASE and Web of Science) until May 24, 2022, followed by a manual search. Based on inclusion and exclusion criteria, publications investigating long-term survival outcomes after RALS vs CLS or LT in endometrial cancer patients were collected. The primary outcomes included overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and disease-free survival (DFS). Fixed effects models or random effects models were employed to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) as appropriate. Heterogeneity and publication bias were also assessed.; Results: RALS and CLS had no difference in OS (HR = 0.962, 95% CI: 0.922-1.004), RFS (HR = 1.096, 95% CI: 0.947-1.296), and DSS (HR = 1.489, 95% CI: 0.713-3.107) for endometrial cancer; however, RALS was significantly associated with favorable OS (HR = 0.682, 95% CI: 0.576-0.807), RFS (HR = 0.793, 95% CI: 0.653-0.964), and DSS (HR = 0.441, 95% CI: 0.298-0.652) when compared with LT. In the subgroup analysis of effect measures and follow-up length, RALS showed comparable or superior RFS/OS to CLS and LT. In early-stage endometrial cancer patients, RALS had similar OS but worse RFS than CLS.; Conclusions: RALS is safe in the management of endometrial cancer, with long-term oncological outcomes equivalent to CLS and superior to LT.; Competing Interests: Declaration of Competing Interest The authors declare they have no conflicts of interest. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Fu, K., et al. (2023). "Pregnancy Outcomes after Uterus-sparing Operative Treatment for Adenomyosis: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 30(12): 1006-1007.
	
Fu, M.-M. and X.-D. Meng (2020). "Assessment of clinical efficacy of traditional Chinese medicine for the management of primary dysmenorrhea in the UK: A protocol of systematic review." Medicine 99(47): e23246.
	Background: This study aims to appraise the clinical efficacy of traditional Chinese medicine (TCM) for the management of patients with primary dysmenorrhea (PD) in the UK.; Methods: We will comprehensively search electronic databases (Cochrane Library, PUBMED/MEDLINE, EMBASE, PsycINFO, AMED, Web of Science, and CNKI) and additional resources for original articles on randomized controlled trials published in English, Chinese, German, Spanish, Korean and Japanese. Outcomes will be the pain intensity, pain duration, menstrual cramps, amount of bleeding, and severity of dysmenorrhea symptoms, quality of life, and adverse events. Two authors will independently check all citations, extract data, and assess study quality. All potential conflicts will be solved through discussion by consulting another experienced author. A narrative synthesis will summarize the characteristics and findings of eligible trials. If it is possible, we will also pool the data and carry out meta-analysis.; Results: The available evidence of the clinical efficacy of TCM for the treatment of PD in UK will be assessed through outcome measurements.; Conclusion: The findings of this study will determine whether or not TCM is effective and safe for the treatment of PD in UK. OSF REGISTRATION NUMBER:: osf.io/jyc95.

Fu, S., et al. (2023). "Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring CCNE1 Amplification." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(9): 1725-1734.
	Purpose: Preclinical cancer models harboring CCNE1 amplification were more sensitive to adavosertib treatment, a WEE1 kinase inhibitor, than models without amplification. Thus, we conducted this phase II study to assess the antitumor activity of adavosertib in patients with CCNE1 -amplified, advanced refractory solid tumors.; Patients and Methods: Patients aged ≥ 18 years with measurable disease and refractory solid tumors harboring CCNE1 amplification, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function were studied. Patients received 300 mg of adavosertib once daily on days 1 through 5 and 8 through 12 of a 21-day cycle. The trial followed Bayesian optimal phase II design. The primary end point was objective response rate (ORR).; Results: Thirty patients were enrolled. The median follow-up duration was 9.9 months. Eight patients had partial responses (PRs), and three had stable disease (SD) ≥ 6 months, with an ORR of 27% (95% CI, 12 to 46), a SD ≥ 6 months/PR rate of 37% (95% CI, 20 to 56), a median progression-free survival duration of 4.1 months (95% CI, 1.8 to 6.4), and a median overall survival duration of 9.9 months (95% CI, 4.8 to 15). Fourteen patients with epithelial ovarian cancer showed an ORR of 36% (95% CI, 13 to 65) and SD ≥ 6 months/PR of 57% (95% CI, 29 to 82), a median progression-free survival duration of 6.3 months (95% CI, 2.4 to 10.2), and a median overall survival duration of 14.9 months (95% CI, 8.9 to 20.9). Common treatment-related toxicities were GI, hematologic toxicities, and fatigue.; Conclusion: Adavosertib monotherapy demonstrates a manageable toxicity profile and promising clinical activity in refractory solid tumors harboring CCNE1 amplification, especially in epithelial ovarian cancer. Further study of adavosertib, alone or in combination with other therapeutic agents, in CCNE1 -amplified epithelial ovarian cancer is warranted.

Fu, W., et al. (2020). "Effect of diverting stoma for rectovaginal fistula: A protocol of systematic review and meta-analysis." Medicine 99(49): e23202.
	BACKGROUND: Rectovaginal fistula (RVF) is a pathologic channel between the anterior wall of the rectum and the posterior wall of the vagina, is rare, and the majority is of traumatic origin. The most common causes are obstetric trauma, local infection, rectal surgery or caused by chronic inflammatory bowel disease. Once the disease will seriously affect the patient's quality of life, and generally not self-healing, most require surgical intervention. At present, diverting stoma is mainly used in patients with severe RVF or complicated RVF or patients with Crohn disease. Due to the lack of large sample, linical studies, its clinical effectiveness is still controversial. The purpose of this systematic review is to evaluate the efficacy of diverting stoma in the treatment of diverting stoma. METHODS: EMBASE, PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese VIP Information will be searched systematically by 2 reviewers from the inception until October 2020. The original study that randomized controlled trials (RCTs), clinical controlled trials (CCTs), nonrandomized control trials (NCTs), and retrospective trials (RTs) of diverting stoma for RVF will be selected. In addition, similar searches will be conducted for the reference lists, researches in progress, and the citation lists of identified publications. Study selection, data extraction, and assessment of the quality will be performed independently by 2 reviewers who have been trained prior to data extraction. A meta-analysis will be conduct if the quantity and quality of the original studies included are satisfactory; otherwise, a descriptive analysis will be conducted. Review Manager 5.4 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) will be using for data synthesis and assessment the risk of bias according by Cochrane Handbook. RESULT: This study will provide a comprehensive review of current evidence for the treatment of diverting stoma on RVF. CONCLUSION: The conclusion of this study will provide a judging basis that whether the treatment of RVF with diverting stoma is effective. INPLASY REGISTRATION NUMBER: INPLASY2020090070.

Fu, Y., et al. (2020). "Efficacy and safety of traditional Chinese herbal formula combined with western medicine for uterine fibroid: A protocol for systematic review and meta-analysis." Medicine 99(36): e22039.
	Background: Clinical studies found that the combination of traditional Chinese herbal formula, and western medicine therapy are better in shrinking fibroids and improve other symptoms. This study aims to systematically evaluate the efficacy and safety traditional Chinese herbal formula combined with western medicine in the treatment of uterine fibroids.; Methods: Randomized controlled trials of traditional Chinese herbal formula combined with western medicine for uterine fibroids patients will be searched in PubMed, Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biological and Medical database (CMB), and Wanfang database from inception to August 2020. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3.; Results: This study will summarize the present evidence by exploring the efficacy and safety of traditional Chinese herbal formula combined with western medicine in the treatment of uterine fibroids CONCLUSIONS:: The findings of the study will help to determine potential benefits of traditional Chinese herbal formula combined with western medicine in the treatment of uterine fibroids.; Ethics and Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.; Osf Registration Number: DOI 10.17605/OSF.IO/XUA8V.

Fu, Y., et al. (2020). "Prophylactic antibiotics for miscarriage surgery: A protocol for systematic review and meta-analysis." Medicine 99(27): e20959.
	Background: Infection is a serious potential consequence of surgery to complete a spontaneous abortion. Antibiotic prophylaxis before some operations has been shown to reduce the risk of postoperative infections. However, for miscarriage surgery, evidence is lacking to show effectiveness.; Methods: In this systematic review, the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, and PUBMED will be searched from inception to May 1, 2020. Randomized controlled trials that assessed the effectiveness and safety of antibiotic prophylaxis for preventing infection for patients undergoing miscarriage surgery will be included. All process of the study selection, data extraction, and methodology evaluation will be carried out by two authors independently. RevMan 5.3 software will be utilized for statistical analysis.; Results: This study will provide a detailed summary of latest evidence related to the effectiveness and safety of antibiotic prophylaxis for preventing infection for patients undergoing miscarriage surgery.; Conclusion: The findings of this study may provide possible guidance for the use of antibiotic prophylaxis for preventing infection for patients undergoing miscarriage surgery.; Dissemination and Ethics: Ethical approval is not required in this study, because it will not collect the original data from individual patient. The results are expected to publish through a peer-reviewed journal.; Systematic Review Registration: PROSPERO CRD CRD42020155643.

Fu, Y., et al. (2019). "Multifaceted self-management interventions for older women with urinary incontinence: A systematic review and narrative synthesis [see correction in link]." BMJ Open 9(8): e028626.
	Objective To synthesise the evidence for the multifaceted self-management interventions for older women with urinary incontinence (UI) and to understand the outcomes associated with these interventions. Design A systematic review and narrative synthesis to identify randomised controlled trials that investigated the effect of multifaceted self-management interventions for older women with UI. Methods MEDLINE, PsycINFO, EMBASE, The Cochrane Library, CINAHL and Applied Social Sciences Index and Abstracts databases were searched (January 1990 to May 2019) using a systematic search strategy, complemented by manually screening the reference lists and citation indexes. Study selection, data extraction and risk of bias assessment were undertaken independently. A narrative synthesis was undertaken in which studies, interventions and outcomes were examined based on the intervention components. The effect size and 95% CI were estimated from each study. Results A total of 13 147 citations were identified and 16 studies were included. There was no study rated as of high quality. Three types of multifaceted interventions were found: those that had an element of pelvic floor muscle exercises (PFME), those with bladder retraining and some with combination behavioural interventions. Outcome measures varied across studies. A statistically significant improvement in incontinence symptoms was reported in the intervention group compared with the control in 15 studies. Conclusion Multifaceted interventions that included PFME, bladder retraining or combination behavioural techniques appear to be useful in some settings for UI management in older women, but the quality of the evidence was poor and unclear. There was insufficient evidence to determine whether any of the combination of components is superior to others in improving UI symptoms. There is a need for high-quality studies to confirm the effectiveness of these interventions and to identify comparative effectiveness.Copyright © 2019 BMJ Publishing Group. All rights reserved.

Fuentes-Márquez, P., et al. (2019). "Physiotherapy interventions for patients with chronic pelvic pain: A systematic review of the literature." Physiotherapy Theory and Practice 35(12): 1131-1138.
	Objective : To summarize the available scientific evidence on physiotherapy interventions in the management of chronic pelvic pain (CPP). Data Sources : A systematic review of randomized controlled trials was performed. An electronic search of MEDLINE, CINAHL, and Web of Science databases was performed to identify relevant randomized trials from 2010-2016. Study Selection : Manuscripts were included if at least one of the comparison groups received a physiotherapy intervention. Studies were assessed in duplicate for data extraction and risk of bias using the Physiotherapy Evidence Database scale PEDro. Data Extraction and Synthesis : Eight of the studies screened met the inclusion criteria. Four manuscripts studied the effects of electrotherapy including intravaginal electrical stimulation, short wave diathermy, respiratory-gated auricular vagal afferent nerve stimulation, percutaneous tibial nerve stimulation, and sono-electro-magnetic therapy with positive results. Three studies focused on manual assessing the efficacy of myofascial versus massage therapy in two of them and ischemic compression for trigger points. Conclusions : Although physiotherapy interventions show some beneficial effects, evidence cannot support the results. Heterogeneity in terms of population phenotype, methodological quality, interpretation of results, and operational definition result in little overall evidence to guide treatment.

Fuh, K., et al. (2022). "A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO/PACLITAXEL-CONTROLLED STUDY OF BATIRAXCEPT IN COMBINATION WITH WEEKLY PACLITAXEL IN PATIENTS WITH PLATINUMRESISTANT RECURRENT OVARIAN CANCER (GOG- 3059/ENGOT OV-66)." International Journal of Gynecological Cancer 32(Supplement 3): A234-A235.
	Objectives Introduction: The AXL receptor and its sole activating ligand, GAS6, are important drivers of metastasis and therapeutic resistance in human cancers. This signaling axis represents an attractive target for therapeutic intervention. The strong picomolar binding affinity between endogenous GAS6 and AXL and the promiscuity of small molecule AXL inhibitors have presented a barrier to specific and potent inhibition of AXL. Batiraxcept (AVB-S6-500) is a recombinant fusion protein with ~200-fold higher affinity for GAS6 than wildtype (WT) AXL. Batiraxcept binds GAS6, inhibiting its interaction with AXL thereby dramatically reducing AXL signaled invasion and migration of highly metastatic cells in vitro and inhibiting metastatic disease in nonclinical models of aggressive human cancers. The Phase 1b study showed no DLTs and established a RP2D of 15 mg/kg IV every 2 weeks with PAC/ PLD. Longer PFS and OS times were observed in patients who had not been previously treated with bevacizumab (bevnaive). Methods High-grade serous PROC, who received 1-4 prior lines randomized (1:1) batiraxcept/PAC or placebo/PAC; stratified by last platinum regimen, prior lines, and prior bevacizumab. The primary endpoint is PFS by RECIST v1.1 assessed by the investigator with OS a secondary endpoint. The primary PFS analysis will be triggered when 130 PFS events occur in the bev-naive; with an interim analysis of OS. Recruitment began April 2021; 252 of ~350 patients have been randomized globally (132 sites) (NCT04729608). Results Trial in progress: there are no available results at the time of submission Conclusions Trial in progress: there are no available conclusions at the time of submission.

Fuhr, L., et al. (2023). "RF1 Brachytherapy dose fractionation preliminary enrollment in a Preference Option Randomized Design Study: Providing the patient voice in a prospective clinical trial." Gynecologic Oncology 173(Supplement 1): S4-S5.
	Objectives: To describe patient preferences regarding adjuvant radiation (RT) treatment options for patients with early stage endometrial cancer following hysterectomy in a preference-option randomized design (PORD) vaginal brachytherapy (VBT) dose fractionation study. Method(s): This prospective multi-center randomized clinical trial (NCT03785288) evaluates patient-reported sexual dysfunction (PRSD) and vaginal shortening following VBT with two commonly used dose fractionation schedules of 7 Gray (Gy) x 3 Fractions (Fx) prescribed to 5 mm depth (Group A) or 4 Gy x 6 Fx prescribed to cylinder surface (Group B). Our hypothesis is that a longer course of 6 Fx results in less toxicity including lower PRSD and vaginal shortening. The protocol was amended to incorporate the PORD in response to direct conversation with patients, as some were hesitant to enroll in a traditional randomized clinical trial given strong treatment preferences. The PORD allows participants the option to switch treatment arms after randomization if they express a strong preference for the alternate arm. This design provides vital patient-centered evidence regarding both the primary quality of life endpoint and treatment preferences. Preliminary data regarding preferences and baseline characteristics was obtained on patients enrolled in the VBT trial to date. Result(s): 70 individuals have enrolled to date across three sites. Recruitment substantially improved following adoption of the PORD, with 64 participants enrolling after this protocol change. 26 participants opted to switch treatment arms (Group AB switching from 3 to 6 Fx and Group BA switching from 6 to 3 Fx). A summary of participants is provided in Fig. 1. The reason for change was documented for each participant, with primary rationales being potential for reduced toxicity (Group AB) and convenience due to travel/time (Group BA). The mean ages were 62 and 66 years for Groups AB and BA, respectively. The mean travel distance to treatment was nearly 50% further for those who opted for the shorter course in Group BA (59.8 vs 83.8 miles). The rate of opt out was similar among the three clinical sites (range 29-50%). Conclusion(s): To our knowledge, this is the first use of PORD in a prospective gynecologic oncology study. Patient preferences for adjuvant VBT following hysterectomy exist. In this ongoing trial, 40% of patients thus far have requested to switch treatment arms, with similar opt-out rates between arms. Patients' priorities regarding their adjuvant RT treatment options differed between convenience and toxicity. Results from this trial will ultimately provide patient-centered evidence to guide shared decision making and inform national guidelines. In the interim, patient preferences regarding VBT should be considered, as these are unique to the individual and may include perceived decreased toxicity, reduced travel burden, and efficiency of treatment. [Formula presented]Copyright © 2023

Fuiano, M., et al. (2019). "Current concepts about treatment options of plantar fibromatosis: A systematic review of the literature." Foot and Ankle Surgery 25(5): 559-564.
	Background: Plantar fibromatosis, or Ledderhose disease, is a benign and hyperproliferative disease of the plantar aponeurosis. There have been described different therapeutic options regarding plantar fibromatosis, both conservative and surgical. The aim of this review is to systematically analyze conservative and operative treatments of plantar fibromatosis described in literature, evaluating which procedure shows the highest success rate and best functional outcome. Method(s): A systematic review of PubMed, Google Scholar and Cochrane reviews computerized database was performed focusing on the different types of treatments for plantar fibromatosis. Research was performed using the keywords "plantar", "fibromatosis", "Ledderhose", "Dupuytren", "foot" in order to identify all papers regarding the treatment of plantar fibromatosis. In addition, the research was extended to the reference list of the relevant articles. A total of 25 citations were obtained from the research and included. Result(s): Considering all the studies, 233 patients were included in this systematic review. 5 studies reported conservative treatment of plantar fibromatosis, with a total of 35 patients included. Operative outcomes are reported for 178 patients (92 male, 86 female), with 196 feet treated. Conclusion(s): Valid conservative methods are presented in literature, with debated results. Some operative options show high recurrence rate; wide excision is recommended in selected cases. Further clinical trials with well-defined and standardized outcome measurements should be necessary in future to better evaluate success rate and complications of the various procedures.Copyright © 2018 European Foot and Ankle Society

Fujita, M., et al. (2023). "Acceptability of self-sampling human papillomavirus test for cervical cancer screening in Japan: A questionnaire survey in the ACCESS trial." PloS One 18(6): e0286909.
	Purpose: In terms of medical policy for cervical cancer prevention, Japan lags far behind other industrialized countries. We initiated a randomized controlled trial to evaluate the self-sampling human papillomavirus (HPV) test as a tool to raise screening uptake and detection of pre-cancer. This study was conducted to explore the acceptability and preference of self-sampling using a subset of the data from this trial.; Methods: A pre-invitation letter was sent to eligible women, aged 30-59 years who had not undergone cervical cancer screening for three or more years. After excluding those who declined to participate in this trial, the remaining women were assigned to the self-sampling and control groups. A second invitation letter was sent to the former group, and those wanting to undergo the self-sampling test ordered the kit. A self-sampling HPV kit, consent form, and a self-administered questionnaire were sent to participants who ordered the test.; Results: Of the 7,340 participants in the self-sampling group, 1,196 (16.3%) administered the test, and 1,192 (99.7%) answered the questionnaire. Acceptability of the test was favorable; 75.3-81.3% of participants agreed with positive impressions (easy, convenient, and clarity of instruction), and 65.1-77.8% disagreed with negative impressions (painful, uncomfortable, and embarrassing). However, only 21.2% were confident in their sampling procedure. Willingness to undergo screening with a self-collected sample was significantly higher than that with a doctor-collected sample (89.3% vs. 49.1%; p<0.001). Willingness to undergo screening with a doctor-collected sample was inversely associated with age and duration without screening (both p<0.001), but that with a self-collected sample was not associated.; Conclusions: Among women who used the self-sampling HPV test, high acceptability was confirmed, while concerns about self-sampling procedures remained. Screening with a self-collected sample was preferred over a doctor-collected sample and the former might alleviate disparities in screening rates.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Fujita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fujiwara, K., et al. (2021). "Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial." Journal of Gynecologic Oncology 32(5): e82.
	OBJECTIVE: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. METHODS: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). RESULTS: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11-1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16-2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. CONCLUSION: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02477644.

Fujiwara, K., et al. (2022). "A randomized phase 3 trial of intraperitoneal versus intravenous carboplatin with dose-dense weekly paclitaxel in patients with ovarian, fallopian tube, or primary peritoneal carcinoma (a GOTIC-001/JGOG-3019/GCIG, iPocc Trial) (LBA 3)." Gynecologic Oncology 166(Supplement 1): S49-S50.
	Objectives: Traditionally, the target of intraperitoneal (IP) chemotherapy for ovarian cancer was patients with minimal residual disease after debulking surgery. However, our pharmacological study suggested that IP carboplatin therapy should also be feasible for patients with larger size residual disease, and our previous phase 2 study demonstrated a satisfactory response rate of IP carboplatin plus dose-dense paclitaxel (ddTCip) regimen in patients with macroscopic residual disease after initial surgery for ovarian (OV), fallopian tube (FT), and primary peritoneal (PP) carcinoma. The purpose of this study is to assess whether IP administration of carboplatin is superior to intravenous (IV) administration of carboplatin (ddTCiv regimen) in OV, FT, and PP carcinoma patients with either minimal or macroscopic residual disease. Method(s): Eligible patients were those with newly diagnosed stages II-IV disease. All patients were to undergo an initial laparotomy or laparoscopy with primary debulking surgery if possible. Before abdomen was closed, patients were randomized to either IV or IP arm. An IP port and catheter was placed if the patient was assigned to IP arm. Chemotherapy regimen was either IV paclitaxel plus IV carboplatin (IV arm) or IV paclitaxel plus IP carboplatin (IP arm). Dose of paclitaxel was 80 mg/m2 Q1W and dose of carboplatin was at an area under the curve (AUC) of 6 Q3W. Each patient was to receive 6 to 8 cycles of chemotherapy. Patients with bulky residual disease were allowed to undergo interval debulking surgery followed by assigned arm regimen up to 8 cycles total. Primary endpoint was PFS, and secondary endpoints included OS, safety, QOL, and cost/benefit. Result(s): Total of 655 patients were randomized between 2010 and 2016 from Japan, Singapore, Korea, New Zealand, USA, and Hong Kong. Stage distribution was II (n= 88), III (n=448), and IV (n=119). Size of residual disease at randomization was either 0 cm (n=163), < 1 cm (n=97), 1-2 cm (n=33), or >2 cm (n=362). Histological types were serous (n=420), endometrioid (n=61), clear cell (n=74), and others (n=100). Median follow-up was 55.7 months. IP chemotherapy significantly improved PFS in the ITT population (HR=0.83, 95%CI:0.69-0.99, p=.041) and in the 602 eligible patients (HR=0.78, 95%CI:0.65-0.94, p=.009). Median PFS for ITT population was 20.7 (95%CI: 18.1-22.8) months in the IV arm and 23.5 (95%CI: 20.5-26.9) months in the IP arm. Median PFS for eligible patients was 20.0 (95%CI: 18.0-22.2) months in the IV arm and 22.9 (95%CI:19.6-26.9) months in the IP arm. Subset analysis showed that the survival benefit was greater in patients with larger size residual disease. Toxicity profile was essentially equivalent in both arms except for catheter-related toxicities (11.8%). Conclusion(s): ddTCip chemotherapy improved the PFS over ddTCiv regimen in patients with OV, FT, and PP carcinoma regardless of the residual tumor size after initial surgery.Copyright © 2022 Elsevier Inc.

Fujiwara, K., et al. (2022). "LBA31 Randomized phase III trial of maintenance chemotherapy with tegafur-uracil versus observation following concurrent chemoradiotherapy for locally advanced cervical cancer, GOTIC-002 LUFT trial." Annals of Oncology 33(Supplement 7): S1398.
	Background: Maintenance chemotherapy with oral tegafur-uracil (UFT) after surgery was shown to prolong survival in lung, breast, gastric and colon cancer. Aim of this trial is to elucidate the efficacy of maintenance chemotherapy using UFT following concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer. Method(s): Eligible patients (pts) are those with FIGO (2008) stage Ib2 -IVa cervical cancer, who have squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. Pts must have completed curative treatment of CCRT with a response of CR or PR. Pts were randomized to observation only (Arm O) or UFT maintenance cohort (Arm UFT) with 1:1 ratio. Dose of oral UFT was 400 mg /day for pts with body surface area (BSA)>= 1.25 m2 and 300 mg/day for pts with BSA < 1.25 m2. Pts received UFT for 2 years without interruption unless disease progression or unacceptable toxicities happened. Primary endpoint was PFS and secondary endpoints included OS, safety and QOL. Significant level was 0.05 (one-side). Result(s): Enrollment started in 2010 and completed in 2018. A total of 351 pts from 55 institutions in Japan were randomized either to Arm O (178 pts) or Arm UFT (173 pts). Safety data was analyzed in 176 pts in Arm O and 168 pts in Arm UFT. Pts characteristics were well balanced between two arms. Most of pts were stage IIb or IIIb, and received CCRT using weekly cisplatin. Median PFS did not reach for both arms. Five-year PFS rates were 61.3% (90%CI: 54.8-67.1) for Arm O and 62.0% (90%CI: 55.4-67.8) for Arm UFT (p=0.634). Hazard ratio (HR) of PFS for Arm UFT vs. Arm O was 0.92 (90%CI: 0.69-1.22). Five-year OS rates were 77.6% (90%CI: 71.8-82.4) for Arm O and 76.1% (90%CI: 70.1-81.1) for Arm UFT (p=0.869). HR of OS for Arm UFT vs. Arm O was 1.04 (90%CI: 0.73-1.47). All grade adverse events (AEs) occurred significantly more in Arm UFT (93.5%) than Arm O (73.9%) (Odds ratio = 5.05, 95%CI: 2.51, 10.15) but most of them were grade 1 or 2. Incidence of AEs >= grade 3 were 15.9% in Arm O and 22.6% in Arm UFT. Conclusion(s): Maintenance chemotherapy using UFT for 2 years after definitive chemoradiation therapy for locally advanced cervical cancer was well tolerated. However, it did not improve either PFS or OS. Clinical trial identification: jRCTs031180174. Legal entity responsible for the study: Gynecologic Oncology Trial and Investigation Consortium (GOTIC). Funding(s): Taiho Pharmaceutical CO., Ltd. Disclosure: K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda, Regenerone, Zeria; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai. All other authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Fujiwara, Y., et al. (2022). "Incidence of hepatotoxicity associated with addition of immune checkpoint blockade to systemic solid tumor therapy: a meta-analysis of phase 3 randomized controlled trials." Cancer Immunology, Immunotherapy 71(12): 2837-2848.
	Hepatotoxicity is a major immune-related adverse event that may become life-threatening. The impact of adding immune checkpoint blockade (ICB) to systemic therapy on the incidence of hepatotoxicity remains unknown. We performed a systematic review and meta-analysis to compare the incidence of hepatotoxicity among patients with cancer who received therapy with and without addition of ICB. PubMed, Embase, Web of Science, and Cochrane Library were searched to select phase 3 randomized controlled trials (RCTs) evaluating the effect of adding ICB to systemic therapy, placebo, or supportive care. The odds ratio (OR) of any grade and grade 3-5 hepatitis, elevations in aspartate aminotransferase (AST), and alanine aminotransferase (ALT) was pooled for meta-analysis. 43 RCTs with 28,905 participants were analyzed. Addition of ICB increased the incidence of hepatitis (any grade: OR, 2.13, 95% confidence interval [CI] 1.52-2.97, grade 3-5: OR, 2.66, 95% CI 1.72-4.11), elevated AST (any grade: OR, 2.16, 95% CI 1.73-2.70, grade 3-5: OR, 2.72, 95% CI 1.86-3.99), and elevated ALT (any grade: OR, 2.01, 95% CI 1.59-2.54, grade 3-5: OR, 2.40, 95% CI 1.62-3.55). Subgroup analysis based on the ICB mechanism revealed no significant heterogeneity among each mechanism for hepatitis (any Grade: I2 = 11.1%, p for heterogeneity = 0.32, grade 3-5: I2 = 0%, p = 0.48). Adding ICB to systemic therapy increases the incidence of hepatotoxicity regardless of the mechanism of ICB. Hepatotoxicity is common and vigilant monitoring of liver function is required during ICB therapy for patients with cancer.Copyright © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Fukuda, F. S., et al. (2023). "Pelvic floor muscles training in women practicing high impact sports: a systematic review." International journal of sports medicine 44(6): 397-405.
	Urinary incontinence (UI) in female sports women can impair their quality-of-life (QoL) and reduce their participation in sport. This review aims to evaluate the effect of pelvic floor muscle training (PFMT) in treating UI in women participating in high-impact sports. Furthermore, to assess the influence of PFMT on pelvic floor muscles (PFM) function and the UI impact on their QoL. For this purpose, a systematic review of randomized controlled trials (RCTs) and non-RCTs was performed. Electronic search was conducted on PubMed, EMBASE, SciELO and Scopus. The quality of evidence was assessed using the PEDro and ROBINS-I scales. The Consensus on Exercise Reporting Template (CERT) was used to assess the quality of PFMT protocols. All studies were available at full-text including incontinent female participants who are practitioners of high-impact sports, investigating PFMT vs control groups(inactive) or undergoing other treatments. Three RCTs and two non-RCTs (104 participants) were analyzed. PFMT provided a significant improvement in UI symptoms with reduction in the frequency (n=3) and the amount of UI (n=5). PFM function was assessed in three studies, and two found improvement in maximal contraction and one in vaginal resting pressure in favor of PFMT. None of the two studies that assessed QoL found a difference after PFMT intervention.

Fukui, M., et al. (2022). "Olaparib-induced cutaneous vasculitis in a patient with recurrent ovarian cancer." European journal of dermatology : EJD 32(5): 655-656.
	
Fukumoto, S., et al. (2023). "Incidence of Hypophosphatemia After Intravenous Administration of Iron: A Matching-Adjusted Indirect Comparison of Data from Japanese Randomized Controlled Trials." Advances in Therapy 40(11): 4877-4888.
	Introduction: Intravenous (IV) administration of iron is considered a safe and efficacious treatment for iron deficiency anemia (IDA), recommended in patients requiring rapid replenishment of iron, or intolerant or unresponsive to oral administration of iron. Recent randomized controlled trials (RCTs) have shown high incidence of hypophosphatemia after administration of two IV iron preparations: saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM). The present study aimed to conduct matching-adjusted indirect comparison (MAIC) of hypophosphatemia incidence with these iron formulations and ferric derisomaltose (FDI) based on data from head-to-head RCTs conducted in Japan.; Methods: A MAIC of hypophosphatemia incidence was conducted on the basis of data from two head-to-head RCTs. The relative odds of hypophosphatemia with FDI versus SFO were obtained from patient-level data from a recent RCT and adjusted for cumulative iron dose, while parametric models of serum phosphate levels from a separate RCT were used to estimate the relative odds of hypophosphatemia with FCM with SFO. An anchored MAIC was then conducted comparing FDI with FCM.; Results: The adjusted odds of experiencing hypophosphatemia were significantly lower with FDI than SFO [odds ratio (OR) of 0.02; 95% confidence interval (CI) 0.01-0.05]. The parametric models of serum phosphate from the RCT comparing FCM with SFO provided an estimated OR of 1.17 for the incidence of hypophosphatemia with FCM versus SFO. Combining the two estimates in the MAIC showed that the odds of experiencing hypophosphatemia would be 52.5 (95% CI 27.7-99.4) times higher with FCM than FDI in patients with IDA associated with heavy menstrual bleeding in Japan.; Conclusions: Direct comparison of patient-level data and a MAIC from two RCTs in Japanese patients with heavy menstrual bleeding indicated that hypophosphatemia is less frequent in patients treated with FDI than those with FCM or SFO. Results are in agreement with RCTs comparing FDI and FCM in patients with various etiologies conducted in the USA and Europe. (© 2023. The Author(s).)

Fundación, I. V. I., et al. (2021). 4-step ASCOT in POI Women to Promote Follicular Rescue.
	No Results Available Drug: G-CSF treatment for Bone marrow derived stem cell Mobilization|Procedure: Platelet Rich Plasma ovarian injection AFC|FSH, AMH and E2 levels|Number of COS and IVF cycle parameters for each patient, initiated before and after treatment.|Menses recovery (YES/NO)|Ovarian function (YES/NO) Female Phase 3 42 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 1912-FIVI-113-SH October 2024

Fung, J. Y. T., et al. (2022). "Effectiveness of eHealth mindfulness-based interventions on cancer-related symptoms among cancer patients and survivors: A systematic review and meta-analysis." Journal of Telemedicine and Telecare: 1357633X221078490.
	OBJECTIVES: This review aimed to synthesize the best available evidence concerning the effectiveness of electronic health, mindfulness-based interventions (eHealth-MBIs) on anxiety, depression, mindfulness and quality of life (QoL) among cancer patients/survivors. METHODS: Published and unpublished studies were retrieved from 10 electronic databases. Two independent authors screened and selected articles, extracted data using a standardized form and appraised the studies with the Cochrane risk of bias assessment tool. Meta-analyses were performed using a random-effect model with Review Manager (REVMAN). Standardized mean differences (SMDs) were used to determine intervention effects. Narrative syntheses were conducted for studies not suitable for meta-analyses. Heterogeneity was identified through I2 and chi-square statistics. Subgroup analyses were performed based on types of controls, age groups and gender. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess overall quality. RESULTS: In total, 18 studies were included. The eHealth-MBIs improved primary outcomes of anxiety (SMD = -0.28) and depression (SMD = -0.24), among cancer patients/survivors with small effect sizes. Effects for the secondary outcomes of QoL (SMD = 0.25) and mindfulness (SMD = 0.29) were observed at short-term follow-up assessments but not at post-intervention. Overall quality was rated as low for the primary and very low for the secondary outcomes. CONCLUSION: The eHealth-MBIs can be offered as a cost-effective and accessible alternative for cancer patients and survivors in healthcare settings. Future research may further explore the effectiveness of eHealth-MBIs based on different types of MBIs, cancer types, modes of delivery and other outcomes such as stress and post-traumatic growth.

Fuoco, V., et al. (2024). "Sentinel node biopsy in gynaecological cancers: state of art and future perspectives." Clinical and Translational Imaging.
	Purpose: This review aims to provide an overview of current knowledge and future perspectives on sentinel node biopsy in gynaecological cancers. Method(s): Literature research in the PubMed/MEDLINE database was carried out to identify relevant studies on sentinel node biopsy in gynaecological cancers. We selected only original studies, published in the English language and including a minimum of nine patients. Result(s): The most relevant results on sentinel node biopsy in gynaecological cancers were summed up, focusing on clinical indications, technical aspects, preoperative and intraoperative procedures and the latest technological advances. Conclusion(s): Sentinel node biopsy has been widely validated in well-selected patients with early-stage vulvar, cervical and endometrial cancers. It is essential to standardise the acquisition protocol, including SPECT/CT imaging, for an improved surgical planning and a personalised approach. Recent technological advances, such as hybrid tracers and intraoperative tools, may efficiently guide gynaecological cancer surgery.Copyright © The Author(s) 2024.

Fusca, L., et al. (2019). "The Effectiveness of Tranexamic Acid at Reducing Blood Loss and Transfusion Requirement for Women Undergoing Myomectomy: A Systematic Review and Meta-analysis." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 41(8): 1185.
	Background: The surgical removal of fibroids can be associated with excessive blood loss requiring transfusion.; Objective: This review sought to determine the effectiveness of tranexamic acid (TA) in reducing perioperative blood loss in women undergoing myomectomy.; Methods: Electronic bibliographic databases were searched from inception until June 3, 2017. The review included RCTs of women of reproductive age with uterine fibroids who were undergoing myomectomy and who received TA or a comparator. Two independent reviewers extracted relevant data, and meta-analysis was performed.; Results: Three studies included women undergoing abdominal myomectomy. TA significantly reduced intraoperative blood loss by a mean difference of 213.1 mL (95% CI -242.4 to -183.7) and postoperative blood loss by a mean difference of 56.3 mL (95% CI -67.8 to -44.8) compared with control arms. However, no significant differences were seen in blood transfusion requirement (relative risk 0.58; 95% CI 0.33-1.00). In one study for women undergoing hysteroscopic myomectomy, TA was not associated with improved outcomes in transfusion requirement and resulted in reduced postoperative hemoglobin levels compared with oxytocin.; Conclusion: Among women undergoing abdominal myomectomy, TA is effective at reducing perioperative blood loss compared with no treatment or placebo. For women undergoing hysteroscopic myomectomy, TA compared with oxytocin is not associated with improved outcomes in transfusion requirement and resulted in reduced postoperative hemoglobin levels. (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Fuschi, A., et al. (2022). "Sexual and functional outcomes after prolapse surgery: a randomized prospective comparison of trocarless transvaginal mesh and pelvic organ prolapse suspension." Langenbeck's archives of surgery 407(4): 1693-1700.
	Purpose: Stress urinary incontinence (SUI) related to pelvic organ prolapse represents a common condition that negatively impacts female sexual activity. Laparoscopic pelvic organ prolapse surgery (POPs) and the anterior repair with a trocar-less trans-vaginal mesh (TTMs) represent two different surgical techniques to treat SUI secondary to POP. This study aimed to report the results of these techniques comparing the sexual and functional outcome improvement.; Materials and Methods: Fifty-nine sexually active female patients, complaining of urodynamic stress incontinence, were enrolled in this prospective study, and simply randomized in two groups: 29 POPs and 30 TTMs. All patients were studied at baseline and 6 months after surgery. Preoperative evaluation included medical history, urodynamic test, Female Sexual Function Index (FSFI), and pelvic magnetic resonance defecography. Six months after surgery, all patients completed the FSFI and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and were investigated with a uroflowmetry test with post-void residual volume (PVR).; Results: At 6 months after surgery, 87% of POPs patients and 79% of TTMs subjects resulted dry. No statistically significant results were obtained in terms of urinary outcomes between the two surgical groups. Regarding sexual function, POPs group exhibited a significant greater improvement of global FSFI (mean: 27.4; SD: 4.31) compared to TTMs group (mean FSFI: 23.56; SD: 2.28; p-value ≤ 0.0001).; Conclusions: Our results indicated that POPs and TTMs lead to satisfactory and safe functional outcomes with a good recovery of urinary continence. Furthermore, POPs, when compared to TTMs, led to a greater improvement of sexual function. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

fxm4g, R. B. R. (2021). "Menorrhagia Control with Two Hormonal IUDs." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: 7596 Hormonal IUDs: levonorgestrel intrauterine systems (52 mg versus 19.5 mg) Group Mirena (52 mg): 73 women with menorrhagia will use Mirena and will be accompanied by 1 year. Group Kyleena (19,5 mg): 73 women with menorrhagia will use Kyleena and will be accompanied by 1 year. Neither the woman nor the principal investigator will know the IUD in use. CONDITION: 8768 Menorrhagia PRIMARY OUTCOME: Considering the margin of 20%, it is thought that the levonorgestrel intrauterine system of 19.5 mg would be similar to the system of 52 mg on the heavy menstrual bleeding control. SECONDARY OUTCOME: Comparison of baseline and 12‐month ferritin levels between Mirena and Kyleena users. Comparison of baseline and 12‐month hematocrit levels between Mirena and Kyleena users. Comparison of baseline and 12‐month hemoglobin levels between Mirena and Kyleena users. Comparison of baseline and 12‐month serum iron levels between Mirena and Kyleena users. Comparison of bleeding pattern between Mirena and Kyleena users by PBAC each 3‐month period, after the insertion of IUD. Comparison of endometrial lining between Mirena and Kyleena users by US scan at baseline and each 3‐month period, after the insertion of IUD. INCLUSION CRITERIA: Women with age between 18 years (complete) ‐ 48 years (incomplete); heavy menstrual bleeding (menorrhagia).

g8mjzk, R. B. R. (2023). "Use of transvaginal non-ablative Radiofrequency in the Treatment of Urinary Incontinence and Vaginal Atrophy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This is a randomized, controlled clinical trial, blinded to study participants. The Randomization was defined by using the method of randomly permuted blocks at randomization.com. The sample size is 62 women, 31 for intevention and 31 for control group. Study participants will undergo three treatment sessions with transvaginal non‐ablative Radiofrequency (RFNATV), with an interval of 3 weeks between sessions. They will be reassessed at each treatment session and one month after the end of the third and final session. Application of the ICIQ‐SF, KHQ, FSFI questionnaire and assessment of pelvic floor muscles strength will be performed. The device used for the application of RFNATV, will be the Spectra Medic, it is developed by the Brazilian company Tonederm (510, Rua Angelo Michelin ‐ Caxias do Sul, RS), released by the National Health Surveillance Agency (ANVISA), through registration number 104.115 .200.22. The transducer to be used will be from the same company. The participant will be in a conventional lithotomy position (gynecological position) when the transducer is introduced. The duration of the application in the groups will be four minutes in each quadrant of the vagina (anterior, posterior, right‐side and left‐side), associated with this, the participant must perform a series of exercises for the pelvic floor muscles, under supervision of the researchers. In the control group, the procedure will be simulated in the same way but the device will be turned off, only using the same sound effects. The time of use will be similar to the time of use in the group and the exercises for the pelvic floor muscles will also be guided under the supervision of the researchers. CONDITION: C12.050.351.500 Genitourinary Syndrome of Menopause. Urinary incontinence PRIMARY OUTCOME: We expect to find an improvement in the symptoms of the menopausal genitourinary syndrome using transvaginal non‐ablative radiofrequency in the treatment of the menopausal genitourinary syndrome, through the application of specific and validated questionnaires for quality of life and sexual satisfaction, as well as the evaluation of vaginal pH, estimating a 5‐point improvement between the pre and post‐treatment evaluations; ; Translated with www.DeepL.com/Translator (free version) SECONDARY OUTCOME: Describe safety and possible side effects induced by Radiofrequency non ablative transvaginal INCLUSION CRITERIA: Postmenopausal women, diagnosed with genitourinary syndrome of menopause, urinary incontinence (stress or mixed with predominance of stress)

Gaba, F., et al. (2023). "Prognosis Following Surgery for Recurrent Ovarian Cancer and Diagnostic Criteria Predictive of Cytoreduction Success: A Systematic Review and Meta-Analysis." Diagnostics (Basel, Switzerland) 13(22).
	For women achieving clinical remission after the completion of initial treatment for epithelial ovarian cancer, 80% with advanced-stage disease will develop recurrence. However, the standard treatment of women with recurrent platinum-sensitive diseases remains poorly defined. Secondary (SCS), tertiary (TCS) or quaternary (QCS) cytoreduction surgery for recurrence has been suggested to be associated with increased overall survival (OS). We searched five databases for studies reporting death rate, OS, cytoreduction rates, post-operative morbidity/mortality and diagnostic models predicting complete cytoreduction in a platinum-sensitive disease recurrence setting. Death rates calculated from raw data were pooled based on a random-effects model. Meta-regression/linear regression was performed to explore the role of complete or optimal cytoreduction as a moderator. Pooled death rates were 45%, 51%, 66% for SCS, TCS and QCS, respectively. Median OS for optimal cytoreduction ranged from 16-91, 24-99 and 39-135 months for SCS, TCS and QCS, respectively. Every 10% increase in complete cytoreduction rates at SCS corresponds to a 7% increase in median OS. Complete cytoreduction rates ranged from 9-100%, 35-90% and 33-100% for SCS, TCS and QCS, respectively. Major post-operative thirty-day morbidity was reported to range from 0-47%, 13-33% and 15-29% for SCS, TCS and QCS, respectively. Thirty-day post-operative mortality was 0-6%, 0-3% and 0-2% for SCS, TCS and QCS, respectively. There were two externally validated diagnostic models predicting complete cytoreduction at SCS, but none for TCS and QCS. In conclusion, our data confirm that maximal effort higher order cytoreductive surgery resulting in complete cytoreduction can improve survival.

Gadducci, A. and D. Aletti Giovanni (2020). "Locally advanced squamous cell carcinoma of the vulva: A challenging question for gynecologic oncologists." Gynecologic Oncology 158(1): 208-217.
	Squamous cell carcinoma of the vulva is a rare female malignancy, with an incidence increasing with age. Unfortunately, one third of the patients are diagnosed with locally advanced disease, which constitutes a clinical challenge for the clinicians who treat these patients. The main challenges are represented by: 1. The primary site of the disease, which can be proximal to anatomical structures like the anal canal posteriorly, or the urethra and the bladder anteriorly, that in some circumstances cannot be spared without a bowel and/or urinary stoma; 2. The locoregional nodes that can be involved by the tumor, and they can be bulky, fixed or ulcerated; 3. The clinical condition of the patient, who may carry several comorbidities. Treatment modalities include radiation with or without chemotherapy, and surgery. In order to preserve the bowel and the urinary function without a permanent stoma, a personalized management with a multimodality approach is warranted. In this systematic review, we first clarify the different definitions of "locally advanced vulvar carcinoma". Secondly, we evaluated the different treatment modalities described in the literature, and the impact of the different treatment strategies on prognosis and on preservation of bowel/urinary function. Finally, we offer a possible algorithm that may help the clinicians in treating patients with these uncommon and challenging situations with a multidisciplinary approach.; Competing Interests: Declaration of competing interest The authors declare no conflict of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gadducci, A., et al. (2019). "Placental site trophoblastic tumor and epithelioid trophoblastic tumor: Clinical and pathological features, prognostic variables and treatment strategy." Gynecologic Oncology 153(3): 684-693.
	Placental site trophoblastic tumor [PSTT] and epithelioid trophoblastic tumor [ETT] are the rarest gestational trophoblastic neoplasias, developing from intermediate trophoblast of the implantation site and chorion leave, respectively. PSTT and ETT share some clinical-pathological features, such as slow growth rates, early stage at presentation, relatively low βhCG levels and poor response to chemotherapy. The mortality rate ranges from 6.5% to 27% for PSTT and from 10% to 24.2% for ETT. Advanced stage, long interval between antecedent pregnancy and diagnosis, and presence of clear cells are the independent prognostic variables for PSTT, and they may be similar for ETT. Hysterectomy can represent the only therapy for early disease, whereas adjuvant chemotherapy should be reserved to patients with poor risk factors, such as an interval from the antecedent pregnancy >4 years, deep myometrial invasion or serosal involvement. Few cases of fertility-sparing treatment in young women have been reported. An individualized multidisciplinary approach, including chemotherapy and debulking surgery with abdominal and/or extra-abdominal procedures, is warranted for advanced disease. EP/EMA and TP/TE are the preferred regimens in this setting. Immunohistochemistry has sometimes shown expression of EGFR, VEGF, MAPK, PDGF-R and PD-L1, and therefore investigational studies on biological agents targeting these molecules are strongly warranted for chemotherapy resistant-disease. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Gadducci, A. and S. Cosio (2022). "Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma." Frontiers in Oncology 12: 914342.
	The ecteinascidins trabectedin and lurbinectedin are very interesting antineoplastic agents, with a favorable toxicity profile and peculiar mechanisms of action. These drugs form adducts in the minor groove of DNA, which produce single-strand breaks (SSBs) and double-strand breaks (DSBs) and trigger a series of events resulting in cell cycle arrest and apoptosis. Moreover, the ecteinascidins interact with the tumor microenvironment, reduce the number of tumor-associated macrophages, and inhibit the secretion of cytokines and chemokines. Trabectedin has been approved by the Federal Drug Administration (FDA) for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-based regimen. Moreover, trabectedin in combination with pegylated liposomal doxorubicin (PLD) has been approved in the European Union for the treatment of platinum-sensitive recurrent ovarian cancer. Lurbinectedin has been approved by the FDA for patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. The review assesses in vitro and in vivo experimental studies on the antineoplastic effects of both ecteinascidins as well as the clinical trials on the activity of trabectedin in uterine sarcoma and ovarian carcinoma and of lurbinectedin in ovarian carcinoma and endometrial carcinoma.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Gadducci and Cosio.)

Gadducci, A., et al. (2022). "Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Epithelial Ovarian Cancer: A Debated Issue for Gynecologic Oncologists." Anticancer Research 42(10): 4659-4665.
	Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely investigated in patients with peritoneal carcinomatosis, including those with epithelial ovarian cancer (EOC), with conflicting results. The hyperthermia enhances drug tissue penetration, synergizes with several cytotoxic drugs including cisplatin, degrades BRCA2, suppresses homologous recombination, and elicits an anticancer immune response. A meta-analysis of retrospective studies including both patients with primary advanced EOC and those with recurrent platinum-sensitive EOC failed to detect a benefit in terms of progression-free survival (PFS) or overall survival (OS) from the addition of HIPEC after surgery. The aim of the present review was to analyze the recent randomized clinical trials designed to assess the value of HIPEC in the management of patients with primary advanced EOC. Although not free from criticism and bias, the available data from two phase III trials seem to suggest that the addition of HIPEC to interval debulking surgery after neoadjuvant chemotherapy significantly improves PFS and OS. Conversely, HIPEC does not appear to offer any advantage after primary debulking surgery. Several phase III trials are currently ongoing on these issues and the use of HIPEC is still a matter of debate in the scientific community. Additional translational research is strongly warranted to detect biological variables able to identify a subset of patients who may have a major benefit from this therapeutic approach. In particular, the clinical outcome of patients who undergo HIPEC should be correlated with BRCA status and homologous recombination repair status. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Gagnon, S., et al. (2022). "Evaluation of Hysteroscopic Endometrectomy: A Reappraisal." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 44(11): 1190-1192.
	Endometrial ablation can be performed using a variety of techniques, including resectoscopic or non-resectoscopic approaches. In this study, we compared 2 resectoscopic endometrial ablation techniques. The first technique was rollerball coagulation followed by endometrectomy (type A; n = 103), and the second was the reverse (type B; n = 107). Besides excessive bleeding in 4 cases, the procedures were uneventful in both groups of patients. We did not encounter uterine perforation or cervical laceration. Satisfaction rates were 97% and 99% with an overall hysterectomy rate of 2.9%. These results compared favorably with those in the literature. The results of our study show that hysteroscopic endometrectomy is effective with few associated complications. (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Gagyor, D., et al. (2022). "Relationship between urethrovesical junction mobility changes and postoperative progression of stress urinary incontinence following sacrospinous ligament fixation - a multicentre prospective study." International Urogynecology Journal 33(Supplement 1): S158-S159.
	Introduction: De novo stress urinary incontinence (SUI) develops following surgery for pelvic organ prolapse in preoperatively asymptomatic patients, affecting 8-10% of women undergoing the surgery. Many patients, particularly those with severe prolapse, may have SUI symptoms masked by urethral obstruction. Posterior deviation of the vaginal axis following sacrospinous ligament fixation (SSF) predisposes to development of anterior compartment defects in approximately 10-20%. Objective(s): The study aimed to assess the relationship between urethrovesical junction (UVJ) descent and development of de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse using the SSF method. This was a secondary analysis of the SAME prospective randomized multicentre study (reg. no. NCT03053479) comparing three approaches to surgery for apical defects - sacropexy, SSF and transvaginal mesh. Since May 2016, five tertiary urogynaecology centres have prospectively recorded history, clinical and anatomical (POP-Q), ultrasound (3D/4D transperineal ultrasound) and subjective (VAS, standardized tools - ICIQ-UI, PSIQ-12, POP SS, PFDI-44) data preoperatively, intraoperatively and postoperatively at 3- month, 12-month, 24-month and 60-month follow-up. Method(s): The subanalysis included 81 patients with apical defects managed by SSF, either right-sided (n=14; 17.3%) or bilateral (n=67; 82.7%). Postoperative follow-up was assessed at 3 months (n=59), 12 months (n=47) and 24 months (n=30). Preoperative demographic data were analyzed. Preoperative and postoperative clinical and anatomical findings were assessed using the Pelvic Organ Prolapse Quantification System (POP-Q). UVJ mobility at rest and with the maximum effort Valsalva manoeuvre was determined using a standardized 3D/4D transperineal ultrasound protocol proposed by Dietz et al. UVJ descent values were calculated as differences in mobility at rest and during Valsalva manoeuvre. De novo SUI and postoperative progression of preexisting SUI were ascertained from history. Patients who had undergone SIU surgery were excluded. Statistical analyses were performed using IBM SPSS Statistics 22 (Armonk, NY: IBM Corp.). The level of statistical significance was set at p<0.05. Result(s): Preoperative demographic data (n=81) were as follows: BMI 27.3 (16.8-44.5), age 67.0 years (31-85), parity 2 (1-6). Concomitant anterior repair was performed in 65.4%. Preoperatively, median measures for POP-Q were Aa 1.0, Ba 4.0 and C 3.0. Postoperative median measures were Aa -1, Ba -1.5, C -7 at 3 months, Aa -1, Ba -1, C -6 at 12 months, and Aa -1, Ba 0, C -5.5 at 24 months. Postoperative progression of SUI was 45.8% at 3 months, 21.3% at 12 months, and 23.3% at 24 months. There were significant differences between preoperative and postoperative UVJ descent values at 3, 12 and 24 months (p< 0.0001). Correlations between UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (p= 0.051-0.883). Correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively) and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (p= 0.691-0.779). Conclusion(s): The study showed significant changes in UVJ descent values preoperatively and at 3, 12 and 24 months after SSF. There were no significant correlations between UVJ descent and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up.

Gágyor, I., et al. (2021). "Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial." Clinical microbiology and infection 27(10): 1441‐1447.
	Objective: We explored whether initial treatment with the herbal drug uva ursi (UU) reduces antibiotic use in women with uncomplicated urinary tract infection (UTI) without increasing symptom burden and complication frequency compared with antibiotic treatment. Methods: A double‐blind randomized controlled trial was conducted in 42 family practices in Germany. The participants were adult women with suspected uncomplicated UTIs receiving either UU 105 mg 3 × 2 tablets for 5 days (intervention) or fosfomycin a 3‐g single dose (control), and their respective placebos. Participants and investigators were blinded. The primary outcome included (1) antibiotic courses day 0–28 as superiority, and (2) symptom burden (sum of daily symptom scores) day 0–7, as non‐inferiority outcome (margin 125%). Clinicaltrials.gov: NCT03151603. Results: Overall, 398 patients were randomly allocated to groups receiving UU (n = 207) and fosfomycin (n = 191). The number of antibiotic courses was 63.6% lower (95% CI 53.6%–71.4%; p < 0.0001) in the UU group than in the fosfomycin group. The ratio of total symptom burden in the UU group compared with control was 136.5% (95% CI 122.7–151.9; p 0.95), failing non‐inferiority. Eight women developed pyelonephritis in the UU group compared with two in the fosfomycin group (mean difference 2.8; 95% CI 0.2–5.9; p 0.067). Adverse events were similar between the groups. Discussion: In women with uncomplicated UTIs, initial treatment with UU reduced antibiotic use but led to a higher symptom burden and more safety concerns than fosfomycin.

Gala, A., et al. (2022). "Does artificial shrinkage prior to fresh blastocyst transfer improve ongoing pregnancy rate? A prospective double blind randomized controlled trial." Human reproduction (Oxford, England) 37: i294‐i295.
	Study question: Does artificial shrinkage (AS) of blastocoelic cavity (BC) prior to fresh elective single blastocyst transfer (SBET) increase ongoing pregnancy rate? Summary answer: Ongoing pregnancy rates were similar with or without AS of blastocoelic cavity. AS does not seem to provide benefit before fresh blastocyst transfer. What is known already: AS of the vitrified blastocysts enhances success rate in frozen embryo transfer cycles. In vitro cultured embryos suffer changes in temperature, pH and osmotic pressure. Moreover, manipulations such as pipetting, fertilization, microscopic observations and changes of dishes can induce oxidative stress and apoptosis. The presence of cell free DNA (cfDNA) in blastocyst fluids could be the consequence of its release from dead cells. The quantity of cfDNA in blastocyst fluids could possibly be related to the rate of cell death. It is thus interesting to estimate whether AS of BC could improve the implantation rate in cycles with fresh blastocyst transfer. Study design, size, duration: Prospective, randomized, double blind controlled study. From May 20th 2018 to June 30th 2021, 150 couples elected for fresh SBET were included in the study and were randomly selected as AS + group (n=100), where AS of blastocoel was performed by laser pulse before fresh blastocyst transfer, and AS‐ group (n=50), where fresh blastocysts were transferred without any additional intervention. Participants/materials, setting, methods: On day 5 after fertilization, one blastocyst with a grade of expansion B3, B4, B5 or B6 and type A or B quality trophectoderm (Gardner and Schoolcraft classification, 1999) was selected for transfer. After replacement, the droplet that contained the embryo from day 3 was collected for cfDNA level quantification. Ongoing pregnancy rate was determined by the visualization of a gestational sac with a foetal heartbeat 6 weeks later and cfDNA was assessed by ALU‐qPCR. Main results and the role of chance: The two groups were similar for age, BMI, infertility duration and cause, stimulation characteristics and embryological parameters. The global ongoing pregnancy rate per transfer after SBET was 49.7 %. The pregnancy rate in the AS + group was slightly higher than in the control group but not significantly (respectively 50.00 % and 48,9 %, p=0,91). cfDNA median value in the AS+ group was comparable to the control group (0.493 (0.219; 0.915) mg/ml and 0.595 (0.271; 1.129) mg/ml respectively (p=0.45)). No link was found between cfDNA rate and clinical pregnancy rate. Limitations, reasons for caution: Patients included in the study are still followed to evaluate the impact of AS on live birth rate, wastage rate, obstetrical and neonatal complications. cfDNA rate was evaluated in spent culture media and not by blastocentesis, which could provide a more accurate quantification. Wider implications of the findings: To our knowledge, this is the first prospective randomized controlled study assessing the benefit of AS of BC before fresh blastocyst transfer. The inclusion of live birth rate is crucial to ascertain the interest of this technique and more studies are needed to improve the use of cfDNA in routine.

Galati, G., et al. (2022). "Folliculogenesis in random start protocols for oocytes cryopreservation: quantitative and qualitative aspects." Reproductive Sciences 29(11): 3260-3265.
	Random start protocols are commonly used for oocytes cryopreservation in women with cancer. However, evidence to support their effectiveness is yet modest. This study aims to compare the quality of ovarian response between the ovary carrying the dominant follicle or the corpus luteum (active ovary) and the contralateral ovary (resting ovary). Women with a diagnosis of malignancy who underwent oocytes cryopreservation were reviewed. The main inclusion criterion was the presence of a unilateral dominant follicle or a unilateral corpus luteum on the first day of ovarian hyperstimulation. The primary outcome was the number of mature oocytes retrieved. Intra-patient comparisons between the two ovaries were made using the nonparametric Wilcoxon test for paired data. Forty-three women were included. The number of mature oocytes retrieved from the active and the resting ovaries did not differ, the median [interquartile range-IQR] being 4 [2-7] and 5 [2-8], respectively (p = 0.09). The rate [IQR] of mature oocytes per developed follicle was 58% [40-80%] and 65% [33-87%], respectively (p = 0.42). In addition, no significant difference emerged when repeating the analyses separately for women carrying dominant follicles and for those carrying corpora lutea. This study failed to detect any detrimental effect of the presence of a dominant follicle or a corpus luteus on the ovarian response to hyperstimulation, thus supporting the validity of random start protocols.Copyright © 2022, The Author(s).

Galazis, N., et al. (2020). "Intraoperative Ultrasound during Fertility-Sparing Surgery: A Systematic Review and Practical Applications." Gynecologic and Obstetric Investigation: 1-22.
	Fertility-sparing surgery (FSS) is an established concept within operative gynaecology. Intraoperative ultrasound (IOUS) has the potential of assessing lesion margins, allowing complete resection with minimal damage to the surrounding healthy tissue and could potentially play a major role in FSS for benign or malignant gynaecological pathologies. In this paper, we review the current literature on the use of IOUS in gynaecological FSS. We also propose technical guidance on the IOUS during FSS. The findings of this review demonstrate that IOUS can assist in the safe resection of disease with high rates of completion, low rates of recurrence and without damage to the nearby healthy reproductive organs. Improved training in transvaginal ultrasonography and minimal access surgery are likely to facilitate the application of IOUS in FSS.

Galliera Ente Ospedaliero, O., et al. (2022). Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer (LEPRE Trial).
	No Results Available Drug: Letrozole tablets|Drug: carboplatin AUC 5 and paclitaxel 175 mg/m2 Progression-free survival (PFS)|Objective Response Rate (ORR)|Predictive effect of ER and PgR (% expression) on response to letrozole in terms of PFS and ORR|Clinical Benefit (CB)|Overall survival (OS)|Safety (Adverse Events) Female Phase 3 132 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 10UCS2018|2020-003066-39 September 22, 2029

Gamba, T., et al. (2023). "Poly (ADP-Ribose) Polymerase Inhibitors in Patients With Urothelial Cancer." Clinical genitourinary cancer 21(5): 509-516.
	Poly ADP-ribose polymerase inhibitors (PARPis) have clinical activity in several cancers. The rationale of their therapeutic use in urothelial cancer (UC) resides in the high homologous-recombination repair (HRR) deficiency (HRD) prevalence and potential cross-sensitivity with platinum-based chemotherapy (PBCT). This review aims to summarize and analyze trials exploring the activity of PARPis in UC, focusing on patients who may benefit from those agents, the best clinical setting for the treatment and the benefit of the association with immune-checkpoint inhibitors (ICIs). We included all the available trials analyzing the activity of PARPis in UC in neoadjuvant, adjuvant, first or subsequent lines, and maintenance setting. We included PARPis in monotherapy and in association with other agents. The results in the maintenance setting are intriguing: ATLANTIS trial showed signals of improved progression-free survival in patients with known HRR aberrations, although the Meet-URO12 trial, with its negative results, suggested the failure of clinical selection based on platinum sensitivity only. Single-agent PARPis in pretreated patients showed discouraging results in an unselected population of chemo-refractory patients. Concerning the association of PARPis with ICIs, several trials are exploring their role in platinum-naïve setting; the results in the advanced setting were globally negative. Prior selection of HRD status is essential to identify patients who might benefit from PARPis. The ideal clinical settings seem to be the maintenance treatment and the combination with ICIs in platinum-naïve patients. Definitive results of ongoing and further trials will delineate the position for PARPis, if any, in UC therapy.; Competing Interests: Disclosure All authors declare no support from any organization for the submitted work; MDM reports honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, GlaxoSmithKline, Amgen, Merck, Takeda for consultancy or participation to advisory boards and direct research funding from Tesaro/GlaxoSmithKline, institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche; other authors declare no conflicts of interest that could appear to have influenced the submitted work. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gambacciani, M. (2023). "Treating where it hurts: tailoring the genitourinary syndrome of menopause treatments." Menopause (New York, N.Y.) 30(5): 463-464.
	Competing Interests: Financial disclosures/conflicts of interest: None reported.

Gamé, X. and V. Phé (2020). "[First-line treatment for non-neurogenic overactive bladder]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 30(14): 904-919.
	INTRODUCTION: The aim was to synthesize current knowledge on overactive bladder (OAB) first-line treatments. METHOD: A systematic literature review based on PubMed, Embase and Google Scholar was conducted in June 2020. RESULTS: Behavioral treatments are based on bladder training and timed voiding using a bladder diary. Lifestyle modifications should be suggested. They include reduction of fluid intake, consumption of caffeine, sodas, weight loss, avoidance of acidic fruit juices and of spicy and acidic salty diet, alkalization of urine by diet and possibly, vitamin D supplementation. Pelvic floor muscle training is mainly based on manual techniques, electrostimulation and/or biofeedback. It has been shown to be effective in treating OAB. In menopausal women, local hormone therapy improves all OAB symptoms. Oral drugs include anticholinergics and beta-3-agonists. Their efficacy is quite similar and superior to placebo. In case of failure of monotherapy, they may be combined. CONCLUSION: Apart from some lifestyle modifications, the efficacy of first-line treatments for OAB has been demonstrated by prospective controlled studies. They may be prescribed individually or in combination.

Gamé, X. and V. Phé (2020). "[Non-neurological overactive bladder and pelvic-perineal pathology in women]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 30(14): 887-894.
	Introduction: The aim was to synthesize current knowledge on overactive bladder (OAB) and female pelvic-perineal diseases.; Method: A systematic literature review based on PubMed, Embase and Google Scholar was conducted in April 2020.; Results: Women with pelvic organ prolapse very often have OAB. Prolapse surgery should be considered if the prolapse is symptomatic and never be indicated in case of overactive bladder symptoms solely. In case of symptomatic prolapse and OAB, pessary and surgical treatments are effective on both pathologies up to 71 % of the cases. OAB may occur in parallel or as part of a menopausal genitourinary syndrome. In the latter case, only local estrogen therapy is effective. OAB may occur alongside stress urinary incontinence (SUI) or be integrated into mixed urinary incontinence. The initial treatment should be based on the most troublesome symptoms. In case of SUI, the outcome of surgical treatment on OAB remains uncertain. De novo, OAB follows prolapse or SUI surgery. It requires investigations to exclude urinary tract infection, bladder outlet obstruction or erosion. The treatment is the same as OAB.; Conclusion: The clinician's challenge is to draw a balance between the OAB and a pelvic-perineal pathology in order to adapt the treatment. (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Gan, L., et al. (2022). "Effect of preoperative group cognitive behavior counseling on anesthesia and postoperative psychology of patients undergoing painless abortion." Modern medicine / 现代医药卫生 38(10): 1650‐1653.
	Objective: To explore the clinical application value of preoperative group cognitive behavioral intervention (GCBC) in pre‐anesthesia evaluation of painless induced abortion. Methods: A total of 240 patients with painless abortion who were admitted to our hospital from January to November 2019 were selected and divided into a control group (CON group) and an intervention group (GCBC group) by random number table method, with 120 cases in each group. The evaluation included 231 cases (115 cases in CON group and 116 cases in GCBC group). The CON group underwent routine diagnosis and treatment procedures and did not participate in GCBC. In the GCBC group, GCBC was performed by a psychologist before surgery, and professional psychological guidance and emotional relaxation therapy were given. The preoperative general data, the incidence of intraoperative respiratory depression, the dosage of propofol per unit time, the incidence of abortion syndrome, postoperative visual analog pain scale (VAS) scores, as well as nausea, the incidence of vomiting, Self‐rating Anxiety Scale (SAS) and Hamilton Depression Scale (HAMD) scores and satisfaction before and after surgery. Results: There was no significant difference in the incidence of bradykinesia and vomiting in the operation center between the two groups (P>0.05); the incidence of respiratory depression, nausea, and abortion syndrome, the dosage of propofol per unit time, and the operation rate of GCBC group The VAS score was significantly lower than that of the CON group, and the difference was statistically significant (P<0.05). The SAS and HAMD scores of the GCBC group decreased more significantly after operation, and the difference was statistically significant compared with the CON group (P<0.05). The satisfaction degree of GCBC group was significantly higher than that of CON group, and the difference was statistically significant (P<0.05). Conclusion: GCBC during preoperative anesthesia assessment can improve postoperative anxiety and depression in patients with abortion surgery, reduce the incidence of intraoperative complications, and improve patients' satisfaction with surgical anesthesia.

Gan, Z. S. and A. L. Smith (2023). "Urinary Incontinence in Elite Female Athletes." Current Urology Reports 24(2): 51-58.
	Purpose of Review: To summarize the current understanding on the epidemiology, pathophysiology, and management strategies of urinary incontinence (UI) in female athletes, highlighting findings specific to nulliparous elite athletes. Recent Findings: UI occurs in about 20-50% of female athletes of all ages and parity status, around 40% for younger nulliparous athletes, and is more prevalent in high-impact sports. Possible contributing factors to UI in female elite athletes include pelvic floor laxity and bladder neck descent, pelvic floor muscle fatigue, low energy availability, and hypermobility syndrome. In female elite athletes, urinary symptoms negatively affect quality of life, although the effects of symptoms on exercise participation are not well understood. Current management strategies are primarily conservative and centered on behavioral modifications and pelvic floor muscle physiotherapy. Summary: UI in female elite athletes appears to be multifactorial. Clarifying how individual factors influence UI in this population will inform athlete counseling, prevention, and treatment strategies.Copyright © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Gangadharan, S. and L. Venkatesan (2021). "Effect of Yoga on Somato-Vegetative Symptoms of Menopausal Women and its Association with Demographic Variables among Yoga and Non-Yoga Groups." Nursing journal of India 112(5): 225‐232.
	Abstract: Background: As longevity increases, the population of menopausal age group women is ever rising even in India. According to the Indian Menopausal Society, the number of menopausal women comes in around 43 million. Fortunately, menopause is now better understood and more openly discussed than ever before. The discipline of Yoga and its methodologies has now been reoriented to suit modern sociological needs and lifestyles. The Objectives of the study are to assess and compare the effectiveness of Yoga on somato-vegetative menopausal symptoms before and after administration of Yoga between Yoga and Non –Yoga groups of menopausal women and to associate the post-test somato-vegetative menopausal symptoms with the selected demographic variables in Yoga and Non-Yoga groups of menopausal women. Methods: A true experimental design involving random assignment to treatment group and control group. The study focuses on Yoga as intervention for menopausal symptoms in somato-vegetative domain. The study was conducted between June 2015 and July 2016. The study was conducted among menopausal women coming under selected Sub Centres in two Primary Health Centres. The sample size was 120 in Yoga group and 120 in Non – Yoga group There were 12 drop outs in the Yoga group. The study adopted cluster sampling technique with randomisation. Results: Majority (61.1%) of them experienced mild Somato-vegetative symptoms and significant (34.3%) of them experienced moderate level of Somato-vegetative symptoms after post-test in the Yoga group. Conclusion: The findings of this study show that there is a reduction in menopausal somato-vegetative symptoms in Yoga group of menopausal women thus proving Yoga intervention to be effective. Women in menopause showed a positive attitude towards performing Yoga as they found it safe in their home settings Key words: Menopause, Somato-vegetative symptoms, Yoga.

Ganho-Ávila, A., et al. (2019). "Efficacy of rTMS in decreasing postnatal depression symptoms: A systematic review." Psychiatry Research 279: 315-322.
	Background: Repetitive Transcranial Magnetic Stimulation (rTMS) has been suggested as an alternative treatment to postnatal depression (PPD).; Objectives: This systematic review aims to examine and summarise evidence on rTMS efficacy in treating depression during the postnatal period.; Methods: We included randomized and non-randomized, single arm, and case report studies, with active rTMS and theta-burst stimulation, sham rTMS, pharmacotherapy or no treatment as comparators. Participants included women with PPD, who were administered rTMS after delivery and up to 12 months postpartum. The observed outcomes were response rate and acceptability.; Results: rTMS shows promising results, with clinically significant decreases in Edinburgh Postnatal Depression Scale (EPDS) scores at week 4 and an overall low risk of dropout.; Limitations: The reduced number of reports, the lack of complete datasets and the serious/high risk of bias of the studies warrant cautious interpretations.; Conclusions and Implications: Despite the promising results, existing evidence on rTMS efficacy is limited, and questions remain on what the most beneficial stimulation parameters should be. Future multicentre randomized clinical trials are needed to better ascertain the clinical efficacy of rTMS in the treatment of depression in the postpartum period. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Gao, C., et al. (2022). "Observation on the application effect of esketamine intravenous injection in artificial abortion." 山东医药 62(11): 56‐58.
	Objective: To observe the anesthesia effect of esketamine in painless induced abortion (abbreviated as painless abortion) and its effect on postoperative depression and recovery of patients. Methods: A total of 160 female patients who were going to undergo painless abortion were selected and randomly divided into esketamine group and control group, 80 cases in each group. In the esketamine group, after intravenous injection of esketamine 0.25 mg/kg, propofol 2 mg/kg was slowly intravenously injected, and propofol 6 mg/(kg·h) was injected intravenously during the operation to maintain anesthesia. The control group was anesthetized with the same dose of propofol as the esketamine group after intravenous injection of sufentanil 0.1 μg/kg. Intraoperative propofol consumption, anesthesia recovery time, observation room stay time, pain visual analog scale (VAS) were recorded in the two groups; the two groups were evaluated by self‐rating depression scale (SDS) 1 day before operation and 3 days after operation, respectively The emotional state of the patients (defined as depression by SDS score ≥53); the quality of recovery (QoR‐40 scale) was used to evaluate the overall quality of recovery in the two groups 3 days after surgery, including physical comfort, emotional state, self‐care ability, Psychological support, pain. The incidence of adverse reactions between the two groups was compared. RESULTS: There was no significant difference in the amount of propofol used, anesthesia recovery time, observation room stay time and VAS between the two groups (all P>0.05). Compared with 1 day before operation, the SDS score and the incidence of depression in the two groups at 3 days after operation were decreased, and the reduction was more obvious in the esketamine group (P<0.05). There was no respiratory depression or skin itching in the two groups. Nausea and vomiting occurred in 3 cases (3.8%), dizziness in 9 cases (11.3%), drowsiness in 6 cases (7.5%) in the esketamine group, and 5 cases (6.3%) in the control group, respectively. ), 5 cases (6.3%), 7 cases (8.9%), and there was no statistical difference between the two groups (all P>0.05). Conclusion: The application of esketamine in painless abortion has better anesthesia effect, and it is helpful to relieve the depression of patients in the short term after operation and improve the quality of postoperative recovery of patients.

Gao, F., et al. (2023). "Current status and progress of endocrine therapy for endometrial carcinoma." Chinese Journal of Cancer Prevention and Treatment 30(11): 693-698.
	Objective To summarize the research progress in endocrine therapy for endometrioid adenocarcinoma (EEC), and systematically review the treatment indications, drug selection, efficacy, and adverse reactions in order to provide useful reference for clinical practice. Methods Using "endocrine therapy, fertility sparing, recurrence and metastasis tumors, endometrial carcinoma" as keywords, searched PubMed, Web of Science, CNKI, and Wanfang Database from January 1, 1961 to December 30, 2022-11-30. A total of 368 English and 96 Chinese literatures were retrieved. Inclusion criteria: (1) current status of endocrine therapy for EEC; (2) early EEC fertility preservation therapy; (3) endocrine therapy for metastatic and recurrent EEC. Exclusion criteria: (1) literatures with small sample size or incomplete data; (2) low quality literature. Finally, 48 related articles were included. Results EEC is a hormone dependent tumor, and estrogen and progesterone play an important role in tumor genesis, progression, and prognosis. The endocrine therapy of EEC can be traced back to the 1960s. Through long-term clinical exploration and practice, currently, the endocrine therapy of EEC is mainly applicable to patients who intend to retain reproductive function in the early stage and some patients with recurrent and metastatic diseases, with good disease control and tolerable adverse reactions. Conclusion The efficacy of endocrine therapy is related to factors such as histological type, expression of estrogen and progesterone receptor in endometrioid adenocarcinoma, and it is necessary to strictly and carefully grasp the indications.Copyright © 2023 Chinese Journal of Cancer Prevention and Treatment, Editorial board. All rights reserved.

Gao, J. (2024). "Effect of Clotrimazole Suppositories on Distribution of Pathogens in Vaginal Secretions and Oxidative Stress in Patients with Vaginitis." Alternative Therapies in Health and Medicine.
	Objective: To evaluate the impact of clotrimazole suppositories on the distribution of vaginal pathogens and oxidative stress in patients with vaginitis. Method(s): A total of 120 patients with vaginitis were recruited from our hospital between January 2021 and December 2022 and were divided into an observation group and a control group using a random envelope method. The control group received treatment with miconazole tablets alone, while the observation group received combined treatment with miconazole tablets and clotrimazole suppositories. Vaginal secretions were collected from the subjects for pathogenic microbial testing. The clinical efficacy of the patients was evaluated, and indicators related to vaginal microecology and microbial imbalance were examined. Serum levels of IL-8, CRP, TNF-alpha, IL-6, PCT, P, LH, FSH, SOD, MDA, NO, and ET-1 were measured in the subjects. Result(s): Among patients with vaginitis, bacteria, fungi, and gram-negative cocci accounted for a relatively high proportion, with bacterial infections accounting for more than 30% and fungal and gram-negative cocci infections both exceeding 10%. Pathogenic infections such as Chlamydia and Trichomonas were less than 10%. The observation group showed significantly higher clinical efficacy compared to the control group, with a statistically significant difference (P < .05). Following treatment, the observation group exhibited significantly lower scores for itching, vaginal discharge, and burning sensation compared to the control group, with a statistically significant difference (P < .05). After treatment, the observation group had significantly lower bacterial density and Nugent score, higher cleanliness, positive lactobacilli rate, and pH value compared to the control group, and the difference was statistically significant (P < .05). After treatment, the observation group demonstrated significantly lower blood levels of IL-8, CRP, TNF-alpha, IL-6, and PCT compared to the control group, with a statistical significance of P < .05. Similarly, the levels of P, LH, and FSH hormones in the observation group were significantly lower than those in the control group, also with a statistical significance of P < .05. In contrast, the levels of SOD and NO in the observation group were significantly higher, while the levels of MDA and ET-1 were significantly lower compared to the control group, with a statistical significance of P < .05. Conclusion(s): Clotrimazole suppositories have been shown to significantly enhance therapeutic outcomes for patients with vaginitis by alleviating inflammation, rebalancing vaginal microecology, regulating hormone secretion, and mitigating oxidative stress.

Gao, J., et al. (2019). "Effects of psychological care in patients with endometriosis: A systematic review protocol." Medicine 98(10): e14772.
	Background: This systematic review will be proposed for investigating the effects of psychological care (PC) in patients with endometriosis.; Methods: We will search the following 7 electronic databases from inception to the present: MEDLINE, EMBASE, SinoMed, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will include randomized controlled trials for evaluating the effects of PC in patients with endometriosis. Cochrane risk of bias tool will be used to evaluate the methodological quality for each included study. Two authors will independently carry out the study selection, data extraction, and methodological quality evaluation. Any disagreements will be solved by a third author through discussion.; Results: This proposed systematic review will use high-quality evidence-based medicine to evaluate the efficacy and safety of PC for endometriosis. The primary outcomes include depression and anxiety. The secondary outcomes consist of pain intensity, health-related quality of life, and adverse events.; Conclusion: The findings of this study will provide convincing evidence to determine whether PC therapy is an effective and safe intervention for patients with endometriosis.; Prospero Registration Number: PROSPERO CRD42019123292.

Gao, J., et al. (2023). "Effect of esmketamine for labor analgesia on development of postpartum depression." Chinese journal of anesthesiology 43(11): 1351‐1354.
	Objective To evaluate the effect of esmketamine for labor analgesia on the occurrence of postpartum depression (PPD). Methods Two hundred and forty‐two cases of nulliparous parturients who selected natural labor and agreed to receive labor analgesia were selected and divided into conventional labor analgesia group (C‐LA group, n= 119) and esmketamine‐based labor analgesia group (E‐LA group, n= 123). The epidural labor analgesia solution contained ropivacaine 100 mg and sufentanil 30 μg in 100 ml of normal saline in C‐LA group. The epidural labor analgesia solution contained ropivacaine 100 mg, sufentanil 30 μg and esketamine 50 mg in 100 ml of normal saline in E‐LA group. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen parturients for depression on admission to the predelivery room and at 2 h and 1, 7 and 42 days after delivery, and EPDS scores were recorded. The patients were diagnosed as having PPD when EPDS score ≥ 9 at 7‐42 days after delivery. Peripheral venous blood samples were collected on admission to the predelivery room and at 1 day after delivery to determine the concentrations of serum estrogen, progesterone, 5‐hydroxytryptamine and cortisol by enzyme linked inmunosorbent assay. Results Compared with group C‐LA, the EPDS scores were significantly decreased on the 1 and 42 days after delivery (P<0.01), no significant change was found in the incidence of PPD (1.7%∕0.8%, P> 0.05), no significant change was found in the concentrations of serum estrogen, progesterone, 5‐hydroxytryptamine and cortisol on admission to the delivery room (P>0.05), and the concentrations of serum progesterone and cortisol were significantly increased on 1 day after delivery in group E‐LA (P<0.05). Conclusions Combination of esketamine is helpful in reducing the risk of postpartum depression when used for epidural labor analgesia, and the mechanism is related to slowing the declines in blood levels of sex hormones and stress hormones after delivery.

Gao, K., et al. (2022). "Intrauterine adhesions combined with Robert's uterus: a case report and literature review." Archives of Gynecology and Obstetrics 306(4): 1069-1075.
	Purpose: To summarize the clinical characteristics and surgical option of Robert's uterus.; Methods: We reported a rare case of Robert's uterus with severe uterine adhesion with successive laparoscopic and hysteroscopic surgery. To our knowledge, such a case has not been reported previously. We also performed a systematic literature review from the PubMed, Embase, and Cochrane databases.; Results: Our patient with Robert's uterus with severe uterine adhesions was successfully treated with hysteroscopic septal resection and hysteroscopic adhesiolysis, and the intractable dysmenorrhea disappeared after the hysteroscopic septal resection. In our study, we analyzed the selected 22 reported cases, 10/22 cases (45.5%) were diagnosed before age 20; 20/22 cases (90.91%) experienced dysmenorrhea, 19/22 cases (86.36%) were with hematometra. 5/22 cases (22.73%) underwent re-operation or a third surgery before diagnosis and management.; Conclusion: Robert's uterus, a rare congenital abnormality of Mullerian duct development, consists of an oblique septum and non-communicating asymmetrical uterine hemi-cavity. The main symptoms are the presence of hematometra and severe dysmenorrhea. Septal resection is the main surgical procedure; however, the rarity and difficulty obtaining a pre-operative diagnosis lead to a high rate of misdiagnosis and second surgery. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gao, L., et al. (2021). "Study on the effect of combination oral contraception and artificial cycle on endometrium regeneration after induced abortion." 中外女性健康研究(21): 1‐2,7.
	Objective: To investigate the effect of estradiol + dydrogesterone artificial cycle therapy and compound oral contraceptive ethinyl estradiol cyproterone on endometrial repair after induced abortion. Methods: 240 cases of induced abortion women were randomly divided into artificial cycle group, COC group and control group. The postoperative vaginal bleeding time, menstrual rehydration time, menstrual volume, endometrial thickness, endometrial blood flow and the incidence of intrauterine adhesions were compared. Results: The vaginal bleeding time in the artificial cycle group and the COC group was shorter than that in the control group, and the menstrual rehydration time was shorter than that in the control group; the menstrual flow in the artificial cycle group was more than that in the control group, while the menstrual flow in the COC group was less than that in the control group; the artificial cycle group The endometrial thickness of the 14 d after operation was greater than that of the control group, and the endometrial thickness of the COC group was smaller than that of the control group; 14 d after operation, the endometrial blood flow in the artificial cycle group and the COC group was better than that in the control group, and there was no significant difference between the artificial cycle group and the COC group. The incidence of intrauterine adhesions in the artificial cycle group and COC group after operation was lower than that in the control group. Conclusion: Both estrogen and progesterone artificial cycles and compound oral contraceptives can effectively reduce postoperative vaginal bleeding time, promote menstrual cramps, and prevent intrauterine adhesions. Artificial cycle treatment can increase endometrial thickness, increase endometrial blood flow, and effectively repair Endometrial, combined short‐acting oral contraceptives can also promote endometrial repair.

Gao, L., et al. (2019). "A comparison of the efficacy of Chinese herbal medicines in the treatment of primary dysmenorrhea: A network meta-analysis protocol." Medicine 98(14): e15100.
	Introduction: Chinese herbal medicines (CHM) have been commonly used in the treatment of primary dysmenorrhea in East Asia. Several systematic reviews have been conducted to assess the clinical efficacy of CHM in the treatment of primary dysmenorrhea. However, their comparative efficacy is still unclear. Therefore, the purpose of this study is to conduct a network meta-analysis (NMA) to systematically compare the advantages of different CHM in the treatment of primary dysmenorrhea.; Methods and Analysis: The following electronic databases will be searched in this study: Web of Science, PubMed, Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan-fang Database. Search terms include (Chinese herbal medicine or Chinese patent medicine or medicinal plants or phytotherapy or traditional medicine or Chinese herbal drugs or plant extracts or herbal medicine or herbal extract or herb or traditional Chinese medicine) and (primary dysmenorrhea or dysmenorrhea or painful menstruation) and (randomized controlled trial). The language will be limited to Chinese and English, and the search date will be up to May 2019. The included studies must be randomized controlled trials (RCTs) with patients diagnosed with primary dysmenorrhea. CHM must be used as interventions in the experimental group. While in the control group, studies that used a different herbal medicine, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo will be included. The primary outcomes include clinical efficacy and visual analog scale (VAS), and the secondary outcomes include adverse events and quality of life. Four reviewers will independently extract the data and assess the qualities of the studies. Statistical analysis will be conducted with R package for each outcome.; Ethics and Dissemination: Ethical approval is not required as this NMA is based on published studies. The completed NMA will be published in a peer-reviewed scientific journal.; Trial Registration Number: PROSPERO CRD42018095254.

Gao, M., et al. (2020). "Traditional Chinese medicine on treating premenstrual syndrome and premenstrual dysphoric disorder: A protocol for systematic review and meta-analysis." Medicine 99(42): e22694.
	Background: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders that manifest themselves in the late luteal phase, and significantly interfere with an individual's daily activities. Clinical evidence suggests that traditional Chinese medicine (TCM) may ease PMS/PMDD symptoms. Here, we review a protocol for exploring the effectiveness and safety of TCM in PMS/PMDD management.; Methods: We will conduct a literature search for randomized controlled trials (RCT) for TCM use in PMS/PMDD on PubMed, web of science, EMBASE, the Cochrane central register of controlled trials (Cochrane Library), Chinese national knowledge infrastructure, Chinese VIP Information, Wanfang, as well as Chinese biomedical literature database. The search included all relevant reports for up to June 1, 2020. The search results were independently analyzed by 2 reviewers who extracted the data. RCT quality will be assessed using the risk-of-bias tool. The evidence will be inspected using the grading of recommendations assessment development and evaluation (GRADE). We will utilize Stata and Revman for systematic review and meta-analysis and analysis of direct and indirect evidence.; Results: Based on current evidence, this study will elucidate the rationale for the utilization of TCM in PMS/PMDD treatment.; Conclusion: Conclusions from this study will inform about the effectiveness and safety of TCM in PMS/PMDD management.; Trial Registration Number: CRD42020192822.; Ethics and Dissemination: Since all data utilized in this systematic review and meta-analysis are published, ethical approval is not needed. Additionally, in the trial of the review process, all data will be evaluated anonymously.

Gao, M., et al. (2021). "Influence of humanistic care based on Carolina care model for ovarian cancer patients on postoperative recovery and quality of life." American journal of translational research 13(4): 3390-3399.
	OBJECTIVE: Our aim was to explore the influence of humanistic care based on Carolina care model on postoperative recovery and quality of life in patients with ovarian cancer (OC). METHODS: In this prospective study, we selected 85 OC patients and randomly divided them into the Carolina group (n = 43) given humanistic care based on Carolina care model and the control group (n = 42) given routine nursing intervention. The postoperative recovery and Functional Assessment of Cancer Therapy-Ovary Cancer (FACT-O) scores were compared between the two groups. RESULTS: After intervention, the time of first flatus and defecation after surgery, the time of first ambulation and the length of average postoperative hospital stay were much shorter, and the pain score, total complication rate, self-rating anxiety scale and self-rating depression scale scores as well as Cortisol, C-reactive protein and fasting blood glucose levels at 48 hours postoperatively were significantly lower in the Carolina group than in the control group. The nursing satisfaction in the Carolina group was markedly higher than that in the control group (97.67% vs. 78.57%, P<0.01). After 3 months of follow-up, the Carolina group showed higher dimension scores of FACT-O than the control group (all P<0.001). CONCLUSION: Humanistic nursing care based on Carolina care model can significantly ameliorate the recovery of OC patients, reduce the physical and psychologic stress response, and effectively enhance the nursing satisfaction and quality of life.

Gao, Q., et al. (2022). "Salvia miltiorrhiza -Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis." Frontiers in Pharmacology 13: 831850.
	Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza -containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods: Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza -containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza -containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16-0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58-2.44). Similarly, the effect of the Salvia miltiorrhiza -containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: -1.11 to -0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza -containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Gao, Shen, Jiang, Luan, Lin, Meng, Wang and Cong.)

Gao, Q., et al. (2023). "Efficacy and safety of sintilimab (anti-PD-1 mAb) for advanced cervical cancer: Results from a Phase II trial." Cancer Research 83(8 Supplement).
	Background: Patients (pts) with advanced cervical cancer who progressed on first-line treatment have no standard therapy and derive limited benefit from currently available treatment. More effective therapeutic strategies are required. This phase II trial was conducted to evaluate the efficacy and safety of IBI310 (anti-CTLA-4 mAb) plus sintilimab (sint) versus sint in pts with recurrent/metastatic cervical cancer. Here we present the efficacy and safety results for pts in sint plus placebo group. Method(s): Pts aged 18-75 years, with histologically or cytologically confirmed cervical cancer who had progressed on or been intolerant to first-line or above platinum-based chemotherapy were enrolled. Pts in sint plus placebo group received sint (200mg) plus placebo IV Q3W for 4 cycles followed by sint monotherapy till disease progression, intolerable toxicity, withdrawal of informed consent, death, or for up to 24 months. The primary endpoint was objective response rate (ORR) assessed by IRRC per RECIST V1.1. The data cutoff date was April 20, 2022. Result(s): Overall, 101 pts were enrolled and received at least one dose of assigned treatment (median age of 53.0 years, 71.3% pts with PD-L1 CPS >=1, 91.0% pts with squamous-cell carcinoma, and 36.6% pts with >=2 lines of prior systemic therapy). The median treatment exposure was 18.0 weeks. The IRRC-assessed confirmed objective response rate (ORR) was 24.5% (95%CI: 16.4%-34.2%), disease control rate was 56.1% (95%CI: 45.7%-66.1%), and median duration of response was not reached. Pts with PD-L1 CPS >=1 showed numerically higher ORR versus those with CPS <1 (32.9% vs 17.2%). With a median follow-up of 8.3 months, median PFS was 2.7 months (95%CI: 1.5-4.3). Median overall survival (OS) was not reached; OS rate was 89.6% (95%CI: 80.9%-94.5%) at 6 months and 65.5% (95%CI: 50.9%-76.7%) at 12 months. Treatmentrelated adverse events (TRAEs) occurred in 75.2% pts, with the most common being anaemia (13.9%), hypothyroidism (12.9%), white blood cell count decreased (12.9%), and hyperthyroidism (10.9%). 18.8% pts experienced CTCAE Grade 3 or higher TRAEs (no TRAE leading to death occurred). TRAEs leading to drug discontinuation occurred in 1 pt (myocarditis, grade 2). Conclusion(s): This study demonstrated favorable antitumor activity and acceptable safety with sintilimab alone over available therapies in >=2 line advanced cervical cancer.

Gao, R., et al. (2020). "Acupuncture and clomiphene citrate for anovulatory infertility: a systematic review and meta-analysis." Acupuncture in medicine : journal of the British Medical Acupuncture Society 38(1): 25-36.
	Objective: To evaluate the comparative effectiveness of acupuncture or acupuncture combined with clomiphene citrate (CC) versus CC alone on the outcomes of anovulatory infertility.; Methods: A literature search in eight databases yielded nine randomised controlled trials (RCTs) that evaluated the comparative effectiveness of acupuncture and CC in anovulatory infertility. Subsequently, data were extracted and the studies were assessed for the quality of their methodological designs and risk of bias. Meta-analyses of the RCT data were conducted.; Results: Nine trials including 1441 women were included in the meta-analysis. There were no significant differences in the rates of pregnancy (odds ratio (OR) 1.18, 95% CI 0.83 to 1.69), ovulation (OR 2.57, 95% CI 0.59 to 11.29) or pregnancy loss (OR 0.98, 95% CI 0.59 to 1.63) when acupuncture was used as an adjuvant therapy alongside CC. Although acupuncture alone did not increase the ovulation rate (OR 0.41, 95% CI 0.11 to 1.49), our review demonstrated superior effects in patients who received acupuncture as a separate treatment modality with respect to both the pregnancy rate (OR 2.34, 95% CI 1.76 to 3.10) and the maximum follicular diameter (mean difference 0.50 mm, 95% CI 0.44 to 0.56 mm) when compared with CC alone. Statistical analysis also showed a reduction in the rate of pregnancy loss when acupuncture was used as a separate treatment compared with CC alone (OR 0.19, 95% CI 0.08 to 0.45).; Conclusions: Based on the above pooled results of the studies, the use of acupuncture as a monotherapy significantly improved the rate of pregnancy among the study participants compared with the use of CC alone. However, any results drawn from these studies should be interpreted with caution when considering the context of clinical practice.

Gao, X., et al. (2022). "Application Effect Analysis on Remifentanil and Propofol Anesthesia in Patients Undergoing Painless Artificial Abortion." 中国社区医师 38(4): 40‐42.
	Objective: To analyze the application effect of remifentanil and propofol anesthesia in patients undergoing painless induced abortion. Methods: A total of 120 patients who underwent painless induced abortion from June 2020 to April 2021 were selected and divided into two groups according to different anesthesia methods, with 60 cases in each group. The control group was anesthetized with propofol; the experimental group was anesthetized with remifentanil and propofol. The levels of surgery‐related indexes, analgesic effects, hemodynamic indexes and the incidence of adverse reactions were compared between the two groups. Results: The dosage of propofol, intraoperative blood loss, postoperative recovery time and incidence of adverse reactions in the experimental group were lower than those in the control group, and the differences were statistically significant (P<0.05). Conclusion: Remifentanil and propofol combined anesthesia in painless induced abortion can not only reduce the dosage of anesthetics, shorten the recovery time, but also improve the analgesic effect, and it will not affect the body's hemodynamics. academic indicators have a greater impact.

Gao, Y., et al. (2021). "Small Extracellular Vesicles: A Novel Avenue for Cancer Management." Frontiers in Oncology 11: 638357.
	Extracellular vesicles are small membrane particles derived from various cell types. EVs are broadly classified as ectosomes or small extracellular vesicles, depending on their biogenesis and cargoes. Numerous studies have shown that EVs regulate multiple physiological and pathophysiological processes. The roles of small extracellular vesicles in cancer growth and metastasis remain to be fully elucidated. As endogenous products, small extracellular vesicles are an ideal drug delivery platform for anticancer agents. However, several aspects of small extracellular vesicle biology remain unclear, hindering the clinical implementation of small extracellular vesicles as biomarkers or anticancer agents. In this review, we summarize the utility of cancer-related small extracellular vesicles as biomarkers to detect early-stage cancers and predict treatment outcomes. We also review findings from preclinical and clinical studies of small extracellular vesicle-based cancer therapies and summarize interventional clinical trials registered in the United States Food and Drug Administration and the Chinese Clinical Trials Registry. Finally, we discuss the main challenges limiting the clinical implementation of small extracellular vesicles and recommend possible approaches to address these challenges.© Copyright © 2021 Gao, Qin, Wan, Sun, Meng, Huang, Hu, Jin and Yang.

Gao, Y., et al. (2021). "Efficacy and safety of niraparib maintenance treatment in platinumsensitive recurrent ovarian cancer after shorter or longer chemotherapy: a post hoc subgroup analysis." International Journal of Gynecological Cancer 31(SUPPL 4): A10‐A11.
	Objectives Traditionally ≥6 cycles of platinum‐containing chemotherapy (Pt‐chemo) are recommended for platinum‐sensitive recurrent ovarian cancer (PSROC). PARP inhibitor maintenance treatment (MT) can be initiated upon clinical complete/ partial response (CR/PR) after ≥4 cycles of chemotherapy. Shorter chemotherapy may improve patient experience without compromising efficacy. This study aims to compare the efficacy and safety of niraparib to placebo as MT administered after ≤4 or >4 cycles of Pt��chemo. Methods This is a post hoc analysis of the published NORA phase III study (NCT03705156). Adults with PSROC and CR/ PR to most recent Pt‐chemo were randomized 2:1 to niraparib or placebo. Primary endpoint was PFS by BICR. Subgroups comprised patients with ≤4 or >4 cycles of most recent Pt‐chemo. Results Table 1 summarizes key baseline characteristics which were overall balanced between groups. Median (95% CI) PFS was 18.37 months (8.54‐not estimable [NE], ≤4‐cycle/niraparib) versus 3.88 months (3.68‐7.43, ≤4‐cycle/placebo; HR=0.36 [p=0.0016]), and was 18.33 months (10.28‐NE, >4‐cycle/niraparib) versus 5.49 months (3.71‐5.75, >4‐cycle/ placebo; HR=0.33 [p<0.0001]) (figure 1). Overall safety profiles were comparable between ≤4‐cycle/niraparib and >4‐ cycle/niraparib, with similar percentages of patients experiencing neutrophil count decrease (60.4%; 58.1%), anemia (50.0%; 55.0%), and platelet count decrease (45.8%; 58.1%). Composition of grade ≥3 TEAEs was consistent with the overall NORA results. Conclusions Similar niraparib‐versus‐placebo PFS benefits were observed after ≤4‐cycle or >4‐cycle Pt‐chemo in CR/PR patients. The efficacy and safety of niraparib MT after shorter Pt‐chemo remain to be verified in larger samples.

Gao, Y., et al. (2020). "Metformin and acupuncture for polycystic ovary syndrome: A protocol for a systematic review and meta-analysis." Medicine 99(14): e19683.
	Backgrounds: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women and can lead to serious social burdens associated with various reproductive and metabolic abnormalities. Studies have demonstrated that metformin can reduce liver glucose in PCOS, lower testosterone levels and increase peripheral insulin sensitivity. There has been also evidence suggesting acupuncture may influence ovulation (release of the egg) by affecting levels of various hormones. We will conduct a systematic review and meta-analysis is to compare the efficacy and safety of metformin with or without acupuncture in PCOS.; Methods and Analysis: We will search publications from Web of Science, PubMed, Science Direct, Wan Fang Data Knowledge Service Platform, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), China National Knowledge Infrastructure (CNKI) and EMBASE, which should be published from inception to February 2020. Two researchers will independently perform the selection of the studies, data extraction, and synthesis. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software. The I test will be used to identify the extent of heterogeneity. We will use the Egger funnel chart to evaluate possible publication biases, in addition, when possible we will perform a subgroup/meta-regression analysis. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).; Results and Conclusion: This study will systematically evaluate the efficacy and safety of Metformin combined with acupuncture in the treatment of PCOS, thus providing evidence to the clinical application of this combination therapy. The results will be published in a peer-reviewed journal.

Gao, Z., et al. (2020). "Impact of Bariatric Surgery on Female Sexual Function in Obese Patients: a Meta-Analysis." Obesity surgery 30(1): 352-364.
	We aimed to make a meta-analysis regarding the effect of bariatric surgery on female sexual function. PubMed, EMBASE, and CENTRAL were searched from database inception through August 2019. Articles were eligible for inclusion if they examined the effect of bariatric surgery on obese women's sexual function assessed by the Female Sexual Functioning Index (FSFI) or/and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Twenty articles were included into meta-analysis. Bariatric surgery was associated with significant increase in the total FSFI score. When parameters included in the FSFI scoring system were separately evaluated, significant improvements were observed in sexual desire, sexual arousal, lubrication, orgasm, sexual satisfaction, and sexual pain. However, the PISQ-12 and FSFI scores in women with pelvic floor disorders (PFDs) were not significantly changed postoperatively. Bariatric surgery improves female sexual function in obese patients, but not in women with PFD.

Gao, Z., et al. (2022). "Acupuncture combined with SSRIs in the treatment of perimenopausal depressive disorder: A protocol for systematic review and meta-analysis." Medicine 101(3): e28558.
	Background: Perimenopausal depressive disorder (PDD) is an affective disorder involving endocrine, neurological, immune, which seriously endangers the physical and mental health of human. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line clinical treatment, have limited efficacy and serious side effects. Acupuncture combined with SSRIs therapy has been widely used clinically because it increases efficacy and reduces side effects. There is a lack of high-quality evidence to assess its efficacy and safety. This study evaluated the effectiveness and safety of acupuncture combined with SSRIs in the treatment of PDD by meta-analysis.; Methods: All randomized controlled trials articles about acupuncture combined with SSRIs treatment of PDD will be searched in databases, such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, Wei Pu from the construction of the library to December 16, 2021. According to Cochrane 5.1 Handbook criteria, two researchers independently screened the literature, extracted data, and evaluated the quality of included studies. Meta-analysis was performed by using RevMan 5.4 and STATA 16.0 software.; Results: This study will summarize the current evidence to evaluate the effectiveness and safety of acupuncture combined with SSRIs for the treatment of PDD.; Conclusion: The results of this study will provide clinicians with new treatment ideas and bring benefits to most patients.; Registration Number: INPLASY2021120080 (DOI number: 10.37766/inplasy2021.12.0080).; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Garcia, P., et al. (2021). "Fertility preservation in endometrial cancer: Perinatal and oncologic outcomes." International Journal of Gynecological Cancer 31(SUPPL 1): A370-A371.
	Introduction/Background* The aim of our study is to evaluate the oncological and perinatal outcomes in young women diagnosed with atypical endometrial hyperplasia (AH) or endometrial cancer (EC) treated with hormone therapy. Methodology A single institutional ambispective study was performed including all patients diagnosed with AH or EC grade 1 without myometrial invasion who received hormone therapy between January 2011 and July 2021. We analyzed the complete response rate and recurrence rate of disease and pregnancy rate in these patients as well as perinatal results (live births rate, type of delivery and perinatal morbidity). In addition, we evaluated complete response rate according to type of hormone therapy, dosage received and treatment length. A review of literature was performed to identify studies involving patients with AH or EC who received fertility sparing management. All statistical analysis were performed using the software SPSS Statistics v.24.0 (IBM Corp., Armonk, NY, USA). Result(s)* There were 6 patients with AH/EC (4 and 2 patients respectively) who received hormone therapy with a mean treatment time of 8.6+/-1.96 months. Hormone therapy with megestrol acetate was carried out in 4 patients (66.6%). Complete remission was achieved in 5 patients (83.3%) and 2 of them (33.3%) attempted pregnancy. Finally, no complications during pregnancy were reported in this 2 patients and both had normal delivery. The rate of live birth was 33.3%. During the follow-up no recurrences were detected and overall survival was 100% Conclusion* Conservative management with progestins of young patients with AH or EC grade 1 limited to the endometrium is an acceptable possibility given the high remission rate and live birth rates achieved. However, definitive surgical treatment cannot be avoided given the high recurrence rate described in the literature.

Garcia-Beltran, C., et al. (2023). "Raised Thyroid-Stimulating Hormone in Girls with Polycystic Ovary Syndrome: Effects of Randomized Interventions." Hormone Research in Paediatrics 96(5): 458-464.
	Introduction: Polycystic ovary syndrome (PCOS) in women associates with raised levels of circulating thyroid-stimulating hormone (TSH) and with high rates of gestational complications. A low range of preconception TSH is followed by low rates of gestational complications. It is unknown whether TSH levels are elevated in adolescents with PCOS and, if so, whether traditional or exploratory treatments can lower them into safe preconception range. We investigated TSH in nonobese adolescents with PCOS, including the effects of randomized interventions.; Methods: Morning TSH was a safety marker in randomized pilot studies comparing the effects of an oral contraceptive (OC) versus those of a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET) in nonobese adolescents with PCOS. A post hoc analysis compared TSH levels in PCOS (N = 62) versus controls, TSH changes on treatment (for 1 year), and TSH levels posttreatment (for 1 year).; Results: Mean TSH levels were higher in PCOS patients than in control girls (p &lt; 0.01). On-treatment TSH levels diverged (p &lt; 0.001), remaining elevated on OC, and descending swiftly on SPIOMET, well into safe preconception range. Posttreatment TSH levels were stable in both subgroups. On-treatment changes of circulating TSH associated to those of liver fat (R = 0.307, p = 0.017).; Conclusion: The endocrine signature of early PCOS is herewith extended to include modestly raised levels of circulating TSH; the normalizing effects of SPIOMET intervention in nonobese adolescents with PCOS are herewith extended to include on- and posttreatment TSH. (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Garcia-Bienes, H. M. and C. C. Sanchez-Mateo (2022). "Cimicifuga racemosa (L.) Nutt. in the treatment of vasomotor symptoms of menopause: a review." Ars Pharmaceutica 63(2): 178-188.
	Introduction: Several studies have shown that preparations based on the rhizomes and roots of black cohosh (Cimicifuga racemosa (L.) Nutt.) can be useful in alleviating the menopausal symptoms. The aim of this study is to perform an update bibliographic review of the efficacy and safety of black cohosh in the treatment of the vasomotor symptoms of menopause. Method(s): A review of published articles from January 2005 to March 2021 in the resource search engine of the University of La Laguna, el punto Q". Randomized and controlled clinical trials, which had the key words in the abstract, text or title, in both English and Spanish, were selected. Result(s): We found 13 trials which met the selection criteria. The studies reviewed showed that the black cohosh preparations (mainly commercial extracts standardized in their content of active ingredients) produced in most of the studies a significant reduction compared to placebo in the vegetative (hot flashes and night sweats) and psychological symptoms of menopause, as well as an improvement in the quality of life. No serious adverse effects were reported at the dose administered. Conclusion(s): Cimicifuga racemosa extracts can be effective and safe for the treatment of vegetative and psychological symptoms of menopause, being well tolerated. However, more clinical trials with a larger number of patients, more extensive, the use of standardized preparations, as well as similar criteria for inclusion and assessment of symptoms, are necessary to obtain more conclusive data.Copyright © 2022 Editorial Universida de Granada. All rights reserved.

Garcia-Donas, J., et al. (2023). "Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03." Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 25(7): 2090-2098.
	Background: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole.; Methods: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings.; Results: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies.; Conclusion: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857).; Gov Identifier: NCT01584297. (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

García-García, I., et al. (2022). "Recurrence Rate and Morbidity after Ultrasound-guided Transvaginal Aspiration of Ultrasound Benign-appearing Adnexal Cystic Masses with and without Sclerotherapy: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 29(2): 204-212.
	Objective: To determine the pooled recurrence rate of benign adnexal masses/cysts (namely simple cyst, endometrioma, hydrosalpinx, peritoneal cyst) after transvaginal ultrasound-guided aspiration, with or without sclerotherapy.; Data Sources: Search of studies published in PubMed and Web of Science databases between January 1990 and December 2020.; Methods of Study Selection: A systematic search strategy was done using Medical Subject Heading terms. Only randomized trials and prospective studies published in English language were included.; Tabulation, Integration, and Results: A total of 395 articles were screened. After applying inclusion and exclusion criteria, 20 studies were included in this review comprising data from 1386 patients with a mean follow-up of 11.4 months (range 0.5-26.5 months). The overall pooled rate of recurrence of adnexal masses was 27%, (95% confidence interval [CI], 18%-39%). Recurrence rate was significantly higher after only aspiration than after sclerotherapy (53%; 95% CI, 46%-60% vs 14%; 95% CI, 8%-22%; p <.001). However, a high heterogeneity across the studies was found. A total of 10 major complications were recorded in the different publications.; Conclusion: In a selected population, aspiration with sclerotherapy had a lower recurrence rate than aspiration without sclerotherapy. However, these results should be interpreted with caution given the heterogeneity of the studies and the paucity of randomized controlled trials. Regarding the adoption of this procedure in routine clinical practice, we believe that aspiration should be considered an experimental procedure as there are few studies addressing long-term recurrence rate, and data comparing this technique with surgical cystectomy are lacking. (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

García-Gómez, E., et al. (2023). "The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome." International Journal of Molecular Sciences 24(7).
	Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and women without the disease (control group). In addition, eight of the PCOS patients underwent intervention with metformin (1500 mg/day) and a carbohydrate-controlled diet (type and quantity) for three months. Clinical and metabolic parameters were determined, and RT-qPCR and MeDIP-qPCR were used to evaluate gene expression and DNA methylation levels, respectively. Decreased expression levels of HOXA10 , GAB1 , and SLC2A4 genes and increased DNA methylation levels of the HOXA10 promoter were found in the endometrium of PCOS patients compared to controls. After metformin and nutritional intervention, some metabolic and clinical variables improved in PCOS patients. This intervention was associated with increased expression of HOXA10 , ESR1, GAB1 , and SLC2A4 genes and reduced DNA methylation levels of the HOXA10 promoter in the endometrium of PCOS women. Our preliminary findings suggest that metformin and a carbohydrate-controlled diet improve endometrial function in PCOS patients, partly by modulating DNA methylation of the HOXA10 gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.

Garcia-Hernandez Samantha, C., et al. (2021). "Metformin does not improve insulin sensitivity over hypocaloric diets in women with polycystic ovary syndrome: a systematic review of 12 studies." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(11): 968-976.
	Objective: To improve insulin action, most clinicians prescribe Metformin in patients with insulin resistance (IR). Women with polycystic ovary syndrome (PCOS), in which IR is an important physiopathological mechanism, treatment with Metformin and specialized diets have been suggested to reduce the patient's IR. However, numerous studies have demonstrated conflicting results with respect to supplementing a diet with Metformin. Therefore, we conducted a meta-analysis to determine if Metformin provides a benefit in conjunction with hypocaloric diets to improve insulin sensitivity in PCOS women.; Methods: PubMed, SCOPUS, LILACS, and EBSCO databases and retrieved studies' bibliographies were searched for prospective studies that investigated the effect between Metformin and hypocaloric diets in PCOS women until April 2020. Pre- and post-intervention values for fasting plasma glucose (FPG), fasting plasma insulin (FPI), and IR indices (HOMA1-IR, ISI, and QUICKI) were extracted. Using Comprehensive Meta-Analysis software, the pooled standard difference in the means (SDM) and 95%CIs were calculated.; Results: 11 publications (12 studies) were selected. There was not a benefit of adding Metformin to a hypocaloric diet with respect to FPG (SDM= -0.17; 95%CI: -0.48-0.14, p = .28) and FPI (SDM = 0.16; 95%CI: -0.24-0.55, p = .45). None of the IR indices also demonstrated any benefit of using Metformin when a diet intervention was implemented (HOMA1-IR: SDM = 0.28; 95%CI: -0.27-0.84, p = .315; ISI: SDM = 0.344; 95%CI: -0.17-0.85, p = .186; QUICKI: SDM= -0.01; 95%CI: -0.42-0.41, p = .968).; Conclusion: Here, we determined that adding Metformin to hypocaloric diets did not improve serum glucose or insulin concentrations as well as IR in PCOS women.

Garcia-Illescas, D., et al. (2024). "The evolving landscape of antibody-drug conjugates in ovarian cancer: new drugs for a new era." Current opinion in obstetrics & gynecology.
	PURPOSE OF REVIEW: This review addresses the emerging role of antibody-drug conjugates (ADCs) in the treatment of ovarian cancer, a field marked by a high need for more effective and targeted therapies. Given the recent advancements in ADC technology and the ongoing challenges in treating ovarian cancer, particularly in late-stage and recurrent cases, this review is both timely and relevant. It synthesizes current research findings and clinical trial data, highlighting the potential of ADCs to revolutionize ovarian cancer treatment. RECENT FINDINGS: The review covers key themes including the mechanism of action of ADCs, their specificity in targeting ovarian cancer cells, recent clinical trial outcomes, advancements in ADC design for improved efficacy and reduced toxicity, and strategies to overcome drug resistance in ovarian cancer. It also addresses the heterogeneity of ovarian cancer and the implications for personalized ADC therapies. SUMMARY: The review underscores the potential of ADCs to significantly impact clinical practice, offering a more effective and personalized treatment approach for ovarian cancer patients. The review suggests a paradigm shift in the treatment of this malignancy, emphasizing the need for further research and development in this area.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

García-López, F.-J., et al. (2023). "Virtual reality to improve low-back pain and pelvic pain during pregnancy: a pilot RCT for a multicenter randomized controlled trial." Frontiers in Medicine 10: 1206799.
	A significant proportion of women experience low back and pelvic pain during and after pregnancy, which can negatively impact their daily lives. Various factors are attributed to these complaints, and many affected women do not receive adequate healthcare. However, there is evidence to support the use of different physiotherapeutic interventions to alleviate these conditions. Virtual reality is a promising complementary treatment to physiotherapy, particularly in improving pain perception and avoidance. The primary objective of this study is to evaluate the efficacy of a four-week program combining VR and physiotherapy compared to standard physiotherapy in pregnant women with low back and pelvic pain, in terms of improving pain avoidance, intensity, disability, and functional level. The study also aims to investigate patient satisfaction with the VR intervention. This research will be conducted through a multi-center randomized controlled clinical trial involving pregnant patients residing in the provinces of Seville and Malaga with a diagnosis of low back and pelvic pain during pregnancy. The alternative hypothesis is that the implementation of a Virtual Reality program in combination with standard physiotherapy will result in better clinical outcomes compared to the current standard intervention, which could lead to the development of new policies and interventions for these pathologies and their consequences. Clinical trial registration : clinicaltrials.gov, identifier NCT05571358.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 García-López, Pastora-Bernal, Moreno-Morales, Estebanez-Pérez, Liñán-González and Martín-Valero.)

Garcia-Ruiz, N. S., et al. (2022). "Preoperative Tamsulosin to Prevent Postoperative Urinary Retention after Pelvic Floor Repair Surgery." Journal of Minimally Invasive Gynecology 29(11 Supplement): S17-S18.
	Study Objective: The purpose of the study is to evaluate the effect of preoperative Tamsulosin on postoperative urinary retention (POUR) in patients undergoing surgery for pelvic organ prolapse. Design(s): A prospective randomized control trial. Setting(s): Patients enrolled in the outpatient clinic setting. Medication given in the preoperative area, the day of surgery. Voiding trial was performed in the post-anesthesia recovery unit (PACU). Patients or Participants: 100 patients were enrolled with 50 in each arm, randomly assigned. Patients diagnosed with pelvic organ prolapse undergoing vaginal or laparoscopic reconstructive pelvic surgery with or without mid-urethral sling. Intervention(s): Oral Tamsulosin 0.4mg given 30-90 minutes before the procedure. Active voiding trial was performed within 4 hours of patients arriving to the PACU. Measurements and Main Results: 48 patients enrolled in the control group and 47 patients in the study group. When comparing demographics, there were no statistically significant differences between the groups except for preoperative uterine prolapse (p<0.05). For the primary outcome, there was no statistically significant difference in incidence of POUR between the 2 groups (p=0.73). A total of 36 patients had POUR; 17 (36.2%) in the study group and 19 (39.6%) in the placebo group. A multivariate cox regression analysis determined that the study group had a hazard risk of 1.1 [95% CI 0.47-2.59] but was not statistically significant (p=0.81). Preoperative uterine prolapse also had an increase hazard risk of 1.25 [95% CI 0.52-3.04] but also failed to meet statistical significance (p=0.62). Postoperative narcotic use (p=1.0) and increased length of surgery (p=0.51) had no increase in POUR. Conclusion(s): In this study, the incidence of POUR was not significantly decreased after a single preoperative dose of Tamsulosin. Receiving Tamsulosin with preoperative uterine prolapse had an increased hazard risk for POUR but was not statistically significant. At this time, we do not recommend a single dose of tamsulosin to decrease POUR after prolapse surgery.Copyright © 2022

Garcia-Sanchez, J., et al. (2021). "Cognitive functions under anti-her2 targeted therapy in cancer patients: A scoping review." Endocrine, Metabolic and Immune Disorders - Drug Targets 21(7): 1163-1170.
	Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite im-proved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients' features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study. Analysis of PubMed, Scopus, Cochrane library and Web of Science databases revealed six studies performed in breast and serous uterine cancer patients analyzing cognitive function under chemotherapy regimens including anti-HER2 drugs. Four of these studies reported small to significant worsening of cognitive function following chemotherapy regimens containing tras-tuzumab (the most widely used anti-HER2 drug). In neoadjuvant settings, and in breast cancer patients, treatment with the new anti-HER-2 drug trastuzumab emtansine seems to induce less cognitive impairment than therapeutic regimens containing chemotherapy and trastuzumab. Acute administration of trastuzumab induced cognitive impairment in gastric cancer mice models, confirming its ability to alter cognitive function in patients. More studies analyzing the impact of anti-HER2 therapy on cognitive function are necessary at preclinical and clinical levels in order to personalize pharmacological treatment and offer cancer patients a better quality of life.Copyright © 2021 Bentham Science Publishers.

Garcia-Sayre, J., et al. (2023). "Two staged phase II clinical trial of Eribulin monotherapy in advanced or recurrent cervical cancer." Gynecologic Oncology 173: 49-57.
	Background: Eribulin a microtubule targeting agent and analog of Halichondrin B, a natural product isolated from marine sponge H. okadai, has proven clinical efficacy in metastatic pretreated breast cancer and liposarcoma. We conducted a 2-stage Phase II study of eribulin in patients with advanced/recurrent cervical cancer to examine its clinical activity and evaluate biomarkers for predictors of response.; Methods: Women with advanced/recurrent cervical cancer after ≤1 prior chemotherapy regimen, measurable disease and ECOG performance status ≤2 were treated with eribulin (1.4 mg/m 2 IV day 1 and 8, every 21 days) with tumor assessments every 2 cycles. Primary endpoint was 6-month progression-free survival (PFS6); secondary were best overall response (RECISTv1.1), toxicity (CTCAEv4.03) and overall survival (OS). Exploratory endpoints were associations of biomarkers with clinical activity. Immunohistochemistry was performed on archival tumor samples. Overexpression was defined when both intensity and distribution scores were ≥ 2.; Results: 32 patients enrolled from 11/2012-5/2017. 29/32 patients had prior chemotherapy with cisplatin/paclitaxel/bevacizumab (n = 12) or cisplatin/gemcitabine (n = 12) as the most common regimens. 14 patients received prior paclitaxel. 1 (3%) had a complete response, 5 (16%) had a partial response and 13 (41%) had stable disease for ORR of 19% (95% CI 8, 37). Those who are paclitaxel naïve experienced the greatest benefit with a 29% ORR (95% CI 12, 54). Patients who received prior paclitaxel responded less favorably than those who did not (p = .002) and had a shorter PFS and OS. Grade 3/4 adverse events occurring in >10% of patients were anemia (n = 12, 38%), neutropenia (n = 7, 22%) and leukopenia (n = 6, 19%). Analysis of correlative predictors of response revealed that patients who did not overexpress βII and BAX were significantly more likely to respond to e`ribulin. PFS was significantly shorter in patients with βII and BAX overexpression, OS was significantly shorter in those with βIII and BAX overexpression. These associations remained after multivariate analysis.; Conclusions: Eribulin shows modest activity in patients with recurrent/advanced cervical cancer with a favorable toxicity profile. Prior paclitaxel exposure is associated with decreased eribulin response. βII, βIII tubulin subtypes and BAX are predictors of response and survival. Eribulin may be an option for women with paclitaxel-naïve recurrent/advanced cervical cancer.; Competing Interests: Declaration of Competing Interest Dr. Lin reports having financial interests in Genentech-Roche. Dr. Louie reports having received grants and research funding from the National Cancer Institute and the United States Department of Defense. Dr. A. Garcia reports participation in the Advisory Board for Biotheranostics Inc. Dr. Roman reports consulting for Cardiff Oncology, Nutcracker Therapeutics and AXDEV as well as participation in the Steering Committee for the Global Coalition of Adaptive Research. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Garcia-Soto, A. E., et al. (2021). "Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer." Cancer 127(13): 2279-2293.
	BACKGROUND: Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this phase 1 trial were to evaluate safety and identify the recommended phase 2 dose of NFV added to concurrent CRT for locally advanced cervical cancer. METHODS: Two dose levels of NFV were evaluated: 875 mg orally twice daily (dose level 1 [DL1]) and 1250 mg twice daily (DL2). NFV was initiated 7 days before CRT and continued through CRT completion. Toxicity, radiographic responses, and pathologic responses were evaluated. Serial tumor biopsies (baseline, after NFV monotherapy, on NFV + CRT, and posttreatment) were evaluated by immunohistochemistry, NanoString, and reverse-phase-protein-array analyses. RESULTS: NFV sensitized cervical cancer cells to radiation, increasing apoptosis and tumor suppression in vivo. Patients (n = 13) with International Federation of Gynecology and Obstetrics stage IIA through IVA squamous cell cervical carcinoma were enrolled, including 7 patients at DL1 and 6 patients at DL2. At DL1, expansion to 6 patients was required after a patient developed a dose-limiting toxicity, whereas no dose-limiting toxicities occurred at DL2. Therefore, DL2 was established as the recommended phase 2 dose. All patients at DL2 completed CRT, and 1 of 6 experienced grade 3 or 4 anemia, nausea, and diarrhea. One recurrence was noted at DL2, with disease outside the radiation field. Ten of 11 evaluable patients remained without evidence of disease at a median follow-up of 50 months. NFV significantly decreased phosphorylated Akt levels in tumors. Cell cycle and cancer pathways also were reduced by NFV and CRT. CONCLUSIONS: NFV with CRT is well tolerated. The response rate is promising compared with historic controls in this patient population and warrants further investigation.

Garcia-Yu, I. A., et al. (2021). "Cocoa-rich chocolate and body composition in postmenopausal women: a randomised clinical trial." British journal of nutrition 125(5): 548‐556.
	During menopause, women undergo a series of physiological changes that include a redistribution of fat tissue. This study was designed to investigate the effect of adding 10 g of cocoa‐rich chocolate to the habitual diet of postmenopausal women daily on body composition. We conducted a 6‐month, two‐arm randomised, controlled trial. Postmenopausal women (57·2 (sd 3·6) years, n 132) were recruited in primary care clinics. Participants in the control group (CG) did not receive any intervention. Those of the intervention group (IG) received 10 g daily of 99 % cocoa chocolate in addition to their habitual diet for 6 months. This quantity comprises 247 kJ (59 kcal) and 65·4 mg of polyphenols. The primary outcomes were the between‐group differences in body composition variables, measured by impendancemetry at the end of the study. The main effect of the intervention showed a favourable reduction in the IG with respect to the CG in body fat mass (‐0·63 kg (95 % CI ‐1·15, ‐0·11), P = 0·019; Cohen's d = ‐0·450) and body fat percentage (‐0·79 % (95 % CI ‐1·31, ‐0·26), P = 0·004; Cohen's d = ‐0·539). A non‐significant decrease was also observed in BMI (‐0·20 kg/m2 (95 % CI ‐0·44, 0·03), P = 0·092; Cohen's d = ‐0·345). Both the body fat mass and the body fat percentage showed a decrease in the IG for the three body segments analysed (trunk, arms and legs). Daily addition of 10 g of cocoa‐rich chocolate to the habitual diet of postmenopausal women reduces their body fat mass and body fat percentage without modifying their weight.

Garcia-Yu Irene, A., et al. (2022). "Effects of cocoa-rich chocolate on cognitive performance in postmenopausal women. A randomised clinical trial [see note]." Nutritional neuroscience 25(6): 1147-1158.
	Objectives: The aim of this research was to evaluate the effects of adding 10 g of cocoa-rich chocolate (99%) to the habitual diet on cognitive performance in postmenopausal women.; Methods: Following a randomised controlled parallel clinical trial, a total of 140 postmenopausal women aged 50-64 were recruited. The intervention group ( n = 73) consumed daily 10 g of chocolate (99% cocoa) in addition to their usual food intake for 6 months, whereas the control group ( n = 67) did not receive any intervention. Attention and executive functions, verbal memory, working memory, phonological fluency, category fluency and clinical variables were assessed at baseline and 6 months.; Results: Trail Making Test B execution time showed a decreased of -12.08 s (95% CI: -23.99, -0.18; p = 0.047) in the intervention group compared to the control group, after adjusting for age, educational level, time elapsed from the beginning of menopause and daily energy consumption (Cohen's d = -0.343). Attention, immediate or delayed verbal memory, phonological or category fluency, and working memory remained unchanged.; Conclusions: The consumption of cocoa-rich (99%) chocolate in addition to the habitual diet could be related to a slight improvement in cognitive performance regarding cognitive flexibility and processing speed in postmenopausal women, with no changes in the rest of the cognitive performance variables evaluated. Trial registration: This clinical trial has been registered at clinicaltrials.gov as NCT03492983.

Gardella, B., et al. (2023). "Aromatase inhibitors in the pharmacotherapy of endometriosis." Expert Opinion on Pharmacotherapy 24(9): 1067-1073.
	Introduction: Endometriosis is a benign chronic inflammatory disease responsible for debilitating pain and decreased quality of life. The traditional treatment is based on estroprogestins, progestins, GnRH analogs, and surgery. Recently, aromatase inhibitors (AIs) demonstrated good efficacy in controlling symptoms and size of endometriotic implants, mostly because they suppress extraovarian estrogen synthesis, which can enhance the hypoestrogenic state ameliorating symptoms of endometriosis.; Areas Covered: Phase I, II, III and IV trials, on the use of AIs used for the treatment of endometriosis, have been retrieved. The pharmacokinetics and pharmacodynamics of third-generation non-steroidal AIs have also been investigated. A MEDLINE search has been performed using the following MeSH keywords: 'endometriosis,' aromatase inhibitors,' 'therapy,' and 'treatment'. The timeframe was from 2010 up to November 2022 including reviews, systematic reviews, reports, case series, and retrospective or prospective trials.; Expert Opinion: AIs have shown good clinical efficacy in combination with hormonal therapy in disease control, and they represent a promising second-line therapy in selected patients, yet more research is needed on alternative drug delivery systems and better control of adverse effects. In postmenopausal women in which surgery is contraindicated, AIs represent an excellent treatment option. Their application in routine clinical practice remains limited by adverse effects.

Garg, A., et al. (2022). "Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS)." Clinical Endocrinology 97(2): 156-164.
	Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the leading cause of anovulatory subfertility. Increased gonadotrophin releasing hormone (GnRH) pulsatility in the hypothalamus results in preferential luteinizing hormone (LH) secretion from the pituitary gland, leading to ovarian hyperandrogenism and oligo/anovulation. The resultant hyperandrogenism reduces negative feedback from sex steroids such as oestradiol and progesterone to the hypothalamus, and thus perpetuates the increase in GnRH pulsatility. GnRH neurons do not have receptors for oestrogen, progesterone, or androgens, and thus the disrupted feedback is hypothesized to occur via upstream neurons. Likely candidates for these upstream regulators of GnRH neuronal pulsatility are Kisspeptin, Neurokinin B (NKB), and Dynorphin neurons (termed KNDy neurons). Growing insight into the neuroendocrine dysfunction underpinning the heightened GnRH pulsatility seen in PCOS has led to research on the use of pharmaceutical agents that specifically target the activity of these KNDy neurons to attenuate symptoms of PCOS. This review aims to highlight the neuroendocrine abnormalities that lead to increased GnRH pulsatility in PCOS, and outline data on recent therapeutic advancements that could potentially be used to treat PCOS. Emerging evidence has investigated the use of neurokinin 3 receptor (NK3R) antagonists as a method of reducing GnRH pulsatility and alleviating features of PCOS such as hyperandrogenism. We also consider other potential mechanisms by which increased GnRH pulsatility is controlled, which could form the basis of future avenues of research. (© 2022 John Wiley & Sons Ltd.)

Garg, K. and S. Zilate (2022). "Umbilical Cord-Derived Mesenchymal Stem Cells for the Treatment of Infertility Due to Premature Ovarian Failure." Cureus 14(10): e30529.
	Females belonging to the reproductive age group may face challenges regarding infertility or miscarriage due to conditions such as premature ovarian failure (POF). It is the condition that happens when a female's ovaries stop working before she is 40. The majority of the causes of POF cases are idiopathic. Other reasons include genetic disorders (Turner's syndrome, bone morphogenetic protein 15 ( BMP15 ) mutation, galactosemia, mutation of forkhead box protein L2 ( FOXL2 ), growth differentiation factor-9 ( GDF9 ), mutation of luteinizing hormone (LH) and follicle-stimulating hormone receptors ( FSHR ), etc.), enzymatic mutation such as aromatase, autoimmune disorders (Addison's disease, vitiligo, systemic lupus erythematosus, myasthenia gravis, autoimmune thyroiditis, autoimmune polyglandular syndrome, etc.), vaccination, and environmental factors (cigarette smoking, toxins, and infections). Many attempts have been made to treat POF by various methods. Some of the methods of treatment include hormone replacement therapy (HRT), melatonin therapy, dehydroepiandrosterone (DHEA) therapy, and stem cell therapy. Stem cell therapy has proven to be the most efficient form for treating POF as compared to all other options. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are the best among the other sources of mesenchymal stem cells (MSCs) for the treatment of POF as they have a painless extraction procedure. They have a tremendous capacity for self-repair and regeneration, which helps them in restoring degenerated ovaries. This review includes information on the causes of POF, its efficacious therapeutic approaches, and the impact of transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) as an option for the therapy of POF. Numerous studies conducted on stem cell therapy prove that it is an effective approach for the treatment of sterility.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Garg et al.)

Garg, S., et al. (2022). "A randomized controlled trial to compare antibiotic prophylaxis in elective gynecological surgeries: Single dose of cefazolin versus single dose of cefazolin and tinidazole." Tzu Chi Medical Journal 34(2): 207-213.
	Objectives: To evaluate if addition of an anti-Anaerobic agent to standard drug-cefazolin for antimicrobial prophylaxis would further decrease postoperative infectious morbidity or not. This is relevant as most of the infections in gynecological surgeries are anaerobic but cefazolin does not protect against anaerobes. Material(s) and Method(s): The study design was a parallel randomized controlled trial. Two hundred patients undergoing benign gynecological surgeries were divided into two groups of 100 each. Group A received 2 g cefazolin 30-60 min before incision and Group B received 2 g cefazolin 30-60 min and 1.6 g tinidazole 60-120 min before incision. The patients were followed for any infectious morbidity for 1 month postoperatively. The analysis was done separately for abdominal, laparoscopic, and vaginal surgeries. The analysis was also done for surgeries according to the wound category, i.e. clean and clean-contaminated. Result(s): The two groups were comparable for age and body mass index (BMI). The two groups were comparable for the factors affecting infectious morbidity such as duration of surgery, blood loss, blood transfusions, duration of hospital stay, and need for additional antibiotics. The postoperative infectious morbidity was analyzed in terms of fever, surgical site infection (SSI), and urinary tract infection (UTI). No patient in vaginal and laparoscopic groups suffered from infectious morbidity. In abdominal surgeries group, postoperative fever occurred in 6/74 (8.1%) and 11/74 patients (14.8%) in Groups A and B, respectively (P = 0.38). SSI occurred in 1/74 (1.3%) and 2/74 (2.7%) patients in Groups A and B, respectively (P = 1.0). UTI occurred in 5/74 patients (6.7%) and 2/74 patients (2.7%) in Groups A and B, respectively (P = 0.44). The data were also analyzed for infectious morbidity for clean and clean-contaminated wound categories, and the results were nonsignificant between both groups for each type of wound category (P > 0.05). Conclusion(s): Cefazolin alone is a sufficient antibiotic prophylaxis for benign gynecological procedures.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Garhofer, G., et al. (2021). "Effect of topical oestradiol eye drops on signs and symptoms of dry eye disease in post-menopausal women." Investigative ophthalmology & visual science 62(8).
	Purpose : Previous evidence indicates that topical oestradiol may be beneficial for patients with dry eye disease (DED), especially in post‐menopausal women. The current phase II study was performed to investigate the effect of a recently developed formulation of oestradiol eye drops on signs and symptoms of DED. Methods : In this randomized, controlled, parallel‐group study, 104 post‐menopausal women with moderate to severe dry eye were included. 17‐β‐oestradiol‐3‐phosphate eye drops (RP101) were administered in three different dosage groups (group 1: 0.5% twice daily, group 2: 0.1% morning and vehicle in the evening, group 3: 0.1% twice daily) and compared to control (group 4: vehicle IntelliGel, twice daily). Treatment was administered for a total period of three months. Schirmer's test II, corneal staining and SANDE symptom score were assessed at baseline and at day 14, 30, 60 and 90 after treatment start. Safety was determined via frequency of adverse events. Results : Schirmer's test II wetting distance significantly increased in all 4 groups from baseline to day 90 without significant difference between groups (group 1: +5.6±6.7; group 2: +3.7±4.2; group 3: +4.8±4.5, group 4: +4.0±5.3 mm/5min). Statistical significance versus baseline occurred earlier in the treatment groups versus the control group. Corneal staining score was significantly reduced after the three‐month treatment period with no significant difference between treatment groups (p<0.001 vs baseline in all groups). Staining of the inferior cornea, however, showed a significantly more pronounced decrease in the highest dose group compared to vehicle (p=0.0463). Symptoms as assessed with the SANDE test decreased at the end of the treatment period in all 4 groups (between ‐18.7±23.5 and ‐26.3±28.0 mm for frequency of symptoms and between ‐13.1±26.8 and ‐24.1±40.2 mm for severity of symptoms). Topical RP101 eye drops were well tolerated on the ocular surface and showed a favorable safety profile. Conclusions : The results of the study indicate that topical RP101 eye drops improve signs and symptoms of DED in post‐menopausal women. The results of the study showed a good safety profile of the topical ophthalmic formulation. Further adequately powered phase III studies are required to assess therapeutic efficacy of topical oestradiol in the treatment of DED.

Gari, R., et al. (2022). "Use of Botulinum Toxin (Botox) in Cases of Refractory Pelvic Floor Muscle Dysfunction." Sexual Medicine Reviews 10(1): 155-161.
	Introduction: Pelvic floor muscle (PFM) dysfunction is a sexual pain disorder characterized by involuntary spasm of pelvic floor muscles (PFMs) around the vagina that interferes with intercourse or any kind of vaginal penetration, making it impossible or extremely painful. Recently, researchers have shown increased interest in botulinum toxin (BoNTA) as an alternative option for refractory cases of PFM dysfunction, especially those that fail first-line treatments. Questions have been raised about the efficacy of BoNTA for the treatment of PFM dysfunction. Objective(s): To provide an updated and comprehensive review on the role of BoNTA in the management of refractory PFM dysfunction. Method(s): We reviewed the literature using a systematic search strategy via PubMed and Google Scholar databases, to identify articles investigating the use of BoNTA in PFM dysfunction. We included studies that explored its indications, mechanism of action, injection dosing and technique, success rate, side effects, and contraindications. Result(s): We identified 20 relevant articles. Of these, 12 were original studies: 7 clinical trials, 1 retrospective cohort study and 4 case reports or case series. Doses of BoNTA that were used in these studies ranged between 20 and 500 units. The most commonly injected sites were levator ani muscles. Success rates varied between 62 and 100 %. Most studies showed no recurrence within 1 year after treatment. The majority of these studies used BoNTA after conventional first-line treatments have failed. Conclusion(s): PFM dysfunction is a debilitating condition that adversely affects quality of life. There is promising evidence to support the use of BoNTA in cases of refractory PFM dysfunction. Further randomized controlled trials are warranted to standardize the use of BoNTA as a treatment option for these cases. Gari R, Alyafi M, Gadi RU, et al. Use of Botulinum Toxin (Botox) in Cases of Refractory Pelvic Floor Muscle Dysfunction. Sex Med Rev 2022;10:155-161.Copyright © 2021 The Authors

Garimella, S., et al. (2021). "A prospective study of oral estrogen versus transdermal estrogen (gel) for hormone replacement frozen embryo transfer cycles." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(6): 515-518.
	AIM: This study was done to compare the efficacy of transdermal estrogen (gel) to oral estradiol in hormone replacement frozen embryo transfer cycles (HR- FET). MATERIALS AND METHODS: This was a prospective study conducted between March 2019 and December 2019. We included 294 HR FET cycles: 156 cycles using oral estrogen tablets (oral group) and 138 cycles using transdermal gel (17 beta estradiol 0.06% w/w) (gel group). Primary objective of this study was to compare endometrial thickness (ET) on the day of progesterone start between the two groups. Our secondary objective was to compare implantation rates (IR), clinical pregnancy rates (CPR), miscarriage rates (MR), duration of estrogen administration, estradiol (E2) levels before the start of progesterone, cycle cancellation rates, patient satisfaction score and undesirable side effects between both the groups. RESULTS: There was no significant difference in the ET, IR, CPR, MR and duration of E2 administration and cycle cancellation rates between both the groups. Patient satisfaction score was significantly higher (8.02 ± 1.07 vs 6.96 ± 0.99 p < .01) and side effects were significantly lower (18.1% vs 55.1%, p≤.01), in the gel group compared to the oral group. CONCLUSION: This study concluded that transdermal estrogen (gel) is equally efficacious as oral estrogen in HR FET cycles with transdermal gel having an added benefit of better patient comfort with less side effects and better safety profile.

Garthwaite, H., et al. (2022). "Multiple pregnancy rate in patients undergoing treatment with clomifene citrate for WHO group II ovulatory disorders: a systematic review." Human fertility (Cambridge, England) 25(4): 618-624.
	Clomifene citrate has long been associated with a multiple pregnancy rate of up to 8-10%. Studies from which these figures originated have largely included patients who received clomifene outside of current national and international treatment guidelines. In January 2020, a systematic review of MEDLINE and relevant reference lists was conducted. Studies were included that reported multiple pregnancy rate in a cohort of patients undergoing treatment with single agent clomifene citrate for WHO group II dysovulatory subfertility. Twelve studies were included in the analysis, with a total sample size of 1,387 patients. The overall multiple pregnancy rate was 3.8% (3.6% twins/0.2% triplets); this dropped to 2.4% (all twins) when studies with a mean BMI ≥35kg/m 2 were excluded. This review suggests that contemporary single agent clomifene use following current guidelines in terms of indication, results in a lower than expected multiple pregnancy rate. Further evidence from clinical practice is required to ensure that patients are adequately informed.

Garutti, M., et al. (2021). "Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review." ESMO Open 6(5): 100276.
	Immune checkpoint inhibitors (i.e. anti-PD1, anti-PDL1, and anti-CTLA4) have revolutionized the therapeutic approach of several cancer types. In a subset of metastatic patients, the duration of the response is so long that a cure might be hypothesized, and a treatment discontinuation strategy could be proposed. Considering that long-term efficacy, some patients could also plan to have a child. Moreover, immunotherapy is moving to the early setting in several diseases including melanoma and breast cancer that are common cancers in young patients. However, there is a paucity of data about their potential detrimental effect on fertility, pregnancy, or sexuality. Herein, we conducted a systematic review with the aim to comprehensively collect the available evidence about fertility, pregnancy, and sexual adverse effects of checkpoint inhibitors in order to help clinicians in daily practice and trialists to develop future studies.

Garzon, S., et al. (2020). "Aromatase inhibitors for the treatment of endometriosis: a systematic review about efficacy, safety and early clinical development." Expert opinion on investigational drugs 29(12): 1377-1388.
	Introduction: Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Therefore, novel therapeutic approaches are necessary.; Areas Covered: This systematic review provides an overview of the efficacy and safety of aromatase inhibitors (AIs) as monotherapies and combination therapies for endometriosis. A systematic literature search was performed from January 1990 to April 2020 in the electronic database MEDLINE, EMBASE, The Cochrane Library, and Web of Science.; Expert Opinion: Based on the critical role of estrogens and the rate-limiting step in the production of the estrogens represented by the aromatase enzyme, AIs are a potential therapeutic option for women affected by endometriosis. Nevertheless, further research is needed to clarify the efficacy of AIs in this setting. Adverse effects need to be investigated to clarify the preventive role of add-back therapy. On that basis, AIs should be adopted only as second-line therapy in patients who are refractory to standard treatments in the setting of scientific research. Further studies should define best dosages, appropriate add-back therapies, administration routes, treatment length, and which patients may benefit more from AIs.

Garzon, S., et al. (2020). "Hysteroscopic Metroplasty for T-Shaped Uterus: A Systematic Review and Meta-analysis of Reproductive Outcomes." Obstetrical & gynecological survey 75(7): 431-444.
	Importance: To date, a comprehensive review on the safety and effectiveness of hysteroscopic metroplasty for T-shaped uterus is still missing.; Objective: To provide a robust synthesis of the available studies investigating reproductive outcomes after hysteroscopic metroplasty for T-shaped uterus.; Evidence Acquisition: We performed a systematic review and meta-analysis (CRD42019143291), using the proportion method with 95% confidence interval (CI). Statistical heterogeneity was assessed by Higgins test ( I 2 ).; Results: We included 11 cohort studies embedding 937 women who underwent hysteroscopic metroplasty. After surgery, the pooled percentage of live birth was 44.54% (95% CI, 36.12%-53.12%; I 2 = 46.22%) and 56.88% (95% CI, 46.48%-66.98%; I 2 = 36.38%) in women with primary infertility and recurrent miscarriage, respectively. In women with recurrent miscarriage, the pooled proportion of miscarriage was 21.46% (95% CI, 15.09%-28.61%; I 2 = 30.18%). The pooled clinical pregnancy proportion in women with primary infertility was 57.19% (95% CI, 43.83%-70.03%; I 2 = 77.81%). The pooled rate of surgical complications was 0.65% (95% CI, 0.20%-1.33%; I 2 = 11.44%).; Conclusions: The hysteroscopic correction of T-shaped uteri was associated with high live birth rate and low miscarriage rate, both in case of primary infertility and recurrent miscarriage.; Relevance: Hysteroscopic metroplasty can be considered a safe and effective strategy to improve reproductive outcomes in case of T-shaped uterus.

Garzon, S., et al. (2021). "Fertility-sparing management for endometrial cancer: Review of the literature." Minerva Medica 112(1): 55-69.
	INTRODUCTION: Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered. EVIDENCE ACQUISITION: We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020. EVIDENCE SYNTHESIS: Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%. CONCLUSION(S): Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.Copyright © 2021 Edizioni Minerva Medica. All rights reserved.

Gaspard, U., et al. (2023). "A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2-vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life." Menopause (New York, N.Y.) 30(5): 480-489.
	Objective: A phase 2 study showed that 15 mg estetrol (E4) alleviates vasomotor symptoms (VMS). Here, we present the effects of E4 15 mg on vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life.; Methods: In a double-blind, placebo-controlled study, postmenopausal participants (n = 257, 40-65 y) were randomized to receive E4 2.5, 5, 10, or 15 mg or placebo once daily for 12 weeks. Outcomes were the vaginal maturation index and maturation value, genitourinary syndrome of menopause score, and the Menopause Rating Scale to assess health-related quality of life. We focused on E4 15 mg, the dose studied in ongoing phase 3 trials, and tested its effect versus placebo at 12 weeks using analysis of covariance.; Results: Least square (LS) mean percentages of parabasal and intermediate cells decreased, whereas superficial cells increased across E4 doses; for E4 15 mg, the respective changes were -10.81% ( P = 0.0017), -20.96% ( P = 0.0037), and +34.17% ( P < 0.0001). E4 15 mg decreased LS mean intensity score for vaginal dryness and dyspareunia (-0.40, P = 0.03, and -0.47, P = 0.0006, respectively); symptom reporting decreased by 41% and 50%, respectively, and shifted to milder intensity categories. The overall Menopause Rating Scale score decreased with E4 15 mg (LS mean, -3.1; P = 0.069) and across doses was associated with a decreasing frequency and severity of VMS ( r = 0.34 and r = 0.31, P < 0.001).; Conclusions: E4 demonstrated estrogenic effects in the vagina and decreased signs of atrophy. E4 15 mg is a promising treatment option also for important menopausal symptoms other than VMS.; Competing Interests: Financial disclosure/conflicts of interest: M.T. and M.J. are employees, U.G. and J.-M.F. are consultants, and W.H.U. and R.A.L. are members of the Scientific Advisory Board of Mithra Pharmaceuticals. W.H.U. received funding from Pharmavite, Los Angeles. H.J.T.C.B. is president and CEO of Pantarhei Bioscience. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

Gaspard, U., et al. (2021). "Effects of estetrol on vaginal cytology, genitourinary syndrome of menopause and health-related wuality of life: results from the E4Relief Phase 2b Study." Maturitas 152: 71.
	Introduction: Estetrol (E4), a native estrogen with selective action in tissues, is in development for the treatment of menopausal symptoms. A dose of E4 15 mg was considered to be the minimal effective dose for alleviating vasomotor symptoms (VMS)*. Here we present the data for vaginal cytology, genitourinary syndrome of menopause (GSM) and health‐related quality of life (HR‐QoL). Design and methods: E4Relief was a multicenter, randomized, dose‐finding, double‐blind, placebo‐controlled study. Postmenopausal women (n=257) aged 40‒65y, received E4 2.5; 5; 10; or 15 mg, or placebo (1:1:1:1:1) once‐daily for 12 weeks (W12). At baseline and W12, we calculated the Vaginal Maturation Value (VMV; a weighted proportion score of vaginal epithelial cell types) and GSM (vaginal dryness, vaginal pain and bleeding associated with sexual activity, vaginal and/or vulvar irritation/itching, and dysuria). HR‐QoL was assessed at baseline, Week 4 (W4), and W12, using the Menopause Rating Scale (MRS). Results were analyzed descriptively and pairwise comparisons versus placebo were performed. Significance level was set at p≤0.05. Results: Participants mean age was 54.2±4.4 yrs and mean BMI was 26.0±3.9 kg/m2. Baseline characteristics of treatment groups were similar. The parabasal cell count decreased significantly vs placebo already at E4 2.5 mg, and conversely, superficial cell count increased vs placebo at W12. Accordingly, the VMV significantly increased for all E4 treatments vs placebo; the largest increase was observed with E4 15 mg (42.5 to 73.1). GSM symptoms improved versus baseline in all E4 groups. GSM scores decreased significantly (improved) by 45% vs baseline for vaginal dryness with E4 15 mg, and particularly for vaginal pain associated with sexual activity by 40‐50% vs baseline with E4 5 mg to 15 mg. HR‐QoL total and domain scores improved in all groups, the highest reduction in total score was reached by E4 15 mg already at W4 (‐47.0% vs baseline). In the 15 mg E4 group, total and all domain scores were significantly improved vs baseline. A highly significant correlation was observed between all MRS domains and VMS frequency and severity, except for the urogenital symptom score. Conclusion: This phase 2 study showed that E4 15 mg is effective for the treatment of the full spectrum of menopausal symptoms. E4 15 mg is not only the minimal effective dose for the treatment of VMS but also effective for the treatment of GSM and improves HR‐QoL and vaginal cytology.

Gates, M., et al. (2023). "Does hormone replacement therapy prevent cognitive decline in postmenopausal women?" The Journal of family practice 72(4): E10-E11.
	NO. Hormone replacement therapy (HRT) does not prevent cognitive decline in postmenopausal women-and in fact, it may slightly increase risk (strength of recommendation, A; systematic review, meta-analysis of randomized controlled trials [RCTs], and individual RCT).

Gatta, G., et al. (2022). "MRI in Pregnancy and Precision Medicine: A Review from Literature." Journal of Personalized Medicine 12(1): 9.
	Magnetic resonance imaging (MRI) offers excellent spatial and contrast resolution for evaluating a wide variety of pathologies, without exposing patients to ionizing radiations. Additionally, MRI offers reproducible diagnostic imaging results that are not operator-dependent, a major advantage over ultrasound. MRI is commonly used in pregnant women to evaluate, most frequently, acute abdominal and pelvic pain or placental abnormalities, as well as neurological or fetal abnormalities, infections, or neoplasms. However, to date, our knowledge about MRI safety during pregnancy, especially about the administration of gadolinium-based contrast agents, which are able to cross the placental barrier, is still limited, raising concerns about possible negative effects on both the mother and the health of the fetus. Contrast agents that are unable to cross the placenta in a way that is safe for the fetus are desirable. In recent years, some preclinical studies, carried out in rodent models, have evaluated the role of long circulating liposomal nanoparticle-based blood-pool gadolinium contrast agents that do not penetrate the placental barrier due to their size and therefore do not expose the fetus to the contrast agent during pregnancy, preserving it from any hypothetical risks. Hence, we performed a literature review focusing on contrast and non-contrast MRI use during pregnancy.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Gauroy, E., et al. (2020). "Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Diagnosis and Management of Recurrent Borderline Ovarian Tumours." Gynecologie Obstetrique Fertilite et Senologie 48(3): 314-321.
	Objective: To provide recommendations for the diagnosis and management of the recurrence of Borderline Ovarian Tumour (BOT). Method(s): Literature review by consulting Pubmed, Medline and Cochrane databases. Result(s): In the case of BOT, most of recurrences are a new BOT without invasive contingent (LE2). In the case of bilateral BOT, bilateral cystectomy is associated with a shorter recurrence time compared to unilateral oophorectomy and contralateral cystectomy (LE2). In recurrent serous BOT, cysts are usually fluid thin-walled with vegetation, corresponding in the IOTA classification to a solid unilocular cyst (LE2). A size of the cyst less than 20 mm is not a sufficient to eliminate the diagnosis of recurrent serous BOT (LE2). Recurrence of mucinous BOT predominantly appears as multilocular or as solid multilocular cysts (LE4). In the case of ovarian preservation, recurrences are most often observed on the preserved ovary(s) (LE2). Non-invasive peritoneal recurrence after initial radical treatment including bilateral hysterectomy and adnexectomy is possible, mainly in patients initially diagnosed with stage II or III BOT with non-invasive peritoneal implant (LE3). Most BOT recurrences are asymptomatic, but clinical examination may allow diagnosis of recurrence (LE2). The normality of the CA 125 dosage does not rule out the diagnosis of recurrent BOT (LE2). A second conservative treatment in the event of recurrence of BOT entails the risk of new recurrence (LE2) with no impact on survival (LE4). Totalization of the adnexectomy in case of recurrence of BOT reduces the risk of new recurrence (LE2). Conservative treatment does not increase the risk of recurrence with non-invasive peritoneal implants (LE4). Conservative treatment may be offered after a first non-invasive recurrence in young women who wish to preserve their fertility (grade C). In the absence of infiltrating tumor, chemotherapy is not indicated. The only cases for which chemotherapy can be considered are those for which there is an infiltrative component in addition to TFO.Copyright © 2020 Elsevier Masson SAS

Gawron, I., et al. (2023). "Nonsteroidal anti-inflammatory drug with a local anesthetic compared to nonsteroidal anti-inflammatory drug alone significantly reduce the pain associated with vaginoscopic office hysteroscopy." European Journal of Obstetrics and Gynecology and Reproductive Biology 288: 61-66.
	Introduction and objectives: Pain is the most common cause of office hysteroscopy (OH) failure. There is no consensus on alleviation of pain during OH. The aim was to compare the effectiveness of pain-relieving methods during OH. Study design: A prospective randomized open-label trial included women subjected to OH. All women received 100 mg of ketoprofen intravenously pre-procedure. Women were randomly assigned to 3 arms: A) no local anesthesia, B) infiltration anesthesia with 20 ml of 1% lidocaine solution, C) paracervical block with 20 ml of 1% lidocaine solution. Karl Storz Bettocchi rigid hysteroscope with a 5 mm operative sheath was used. Intensity of pain in numeric rating scale (NRS), intensity of cervical bleeding, frequency of vasovagal episodes, and failure rate were compared. Result(s): The study involved 201 women, 67 in each arm. NRS value during OH was higher in arm A than in B and C (6.3 vs. 5.1 vs. 5.0; p = 0.01). NRS value after OH did not differ and in all arms pain was imperceptible (p = 0.007). Cervical bleeding was more frequent in arm B than in A and C (76.1% vs. 33.4% vs. 35.9%; p < 0.0001), but its intensity did not differ from the other arms (p = 0.3). Vasovagal episode was most common in arm B (p = 0.048). There was no difference in the failure rate between the arms (p = 0.08). Conclusion(s): The paracervical block, albeit technically the most laborious, has proven to be the most beneficial for the patient in terms of overall comfort and for the surgeon regarding feasibility.Copyright © 2023

Gayathri, D., et al. (2021). "A systematic review to evaluate current Digital Pain Medicine tools (ELEMI Project)."
	
Gayathri, R., et al. (2021). "Safety and tolerability of solifenacin in children and adolescents with overactive bladder."
	
gbffqc, R. B. R. (2023). "Does nurse counseling reduce anxiety in women starting assisted reproductive treatments?" International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This is a randomized controlled trial with two arms, single‐blind. After enrolment, the 100 participants will be randomly allocated into two groups using a computer program. Experimental group: 50 women with infertility will have a nurse consultation in person, lasting 40 to 60 minutes. Control group: 50 women with infertility will watch a 20 min video recorded by the same nurse with the same information provided in the consultation. The consultations and the video sessions will be carried out in the university hospital. CONDITION: F41.1 Female infertility, unspecified PRIMARY OUTCOME: We expect to find a decrease in the anxiety levels of the participants, as assessed by the State‐Trait Anxiety Inventory (STAI), with a variation of at least 6 points between pre‐ and post‐intervention tests. SECONDARY OUTCOME: No secondary outcomes will be assessed. INCLUSION CRITERIA: Infertility; IVF/ICSI

Ge, J. and X. Han (2021). "Effect of sufentanil or remifentanil combined with propofol during painless induced abortion." 中国计划生育学杂志 29(12): 2668‐2670.
	Objective: To compare the effect of sufentanil and remifentanil combined with propofol in painless induced abortion. Methods: A total of 126 patients who underwent painless induced abortion in the obstetrics department of our hospital from August 2017 to December 2018 were selected. They were divided into sufentanil combined with propofol group or remifentanil combined with propofol group by random number table method, 63 cases in each group. The anesthesia effect, vital signs before and after anesthesia, and adverse reactions were compared between the two groups. Results: The qualified rate of anesthesia effect was 61 cases (96.8%) in sufentanil combined with propofol group and 62 cases (98.4%) in remifentanil combined with propofol group, there was no difference between the two groups (P>0.05). After anesthesia, there was no difference in heart rate and blood oxygen saturation between the two groups, but the mean arterial pressure in the sufentanil plus propofol group was higher than that in the remifentanil plus propofol group (P<0.05). Postoperatively, 4 cases of dizziness, 2 cases of nausea and vomiting, 2 cases of bradycardia occurred in the sufentanil combined with propofol group, with a total adverse event rate of 12.7%; 3 cases of dizziness occurred in the remifentanil combined with propofol group, There were 5 cases of nausea and vomiting and 1 case of bradycardia. The total incidence of adverse events was 14.3%, and there was no difference between the two groups (P<0.05). Conclusion: The compound intravenous anesthesia scheme (sufentanil combined with propofol or remifentanil combined with propofol) can achieve satisfactory anesthesia effect in painless artificial abortion operation. The anesthesia effect and incidence of adverse reactions in the two groups No significant difference.

Gecgil, E. and G. Baysoy (2023). "DIET FOR THE SOUL: MEDITERENNEAN DIET IS BENEFICIAL FOR POSTPARTUM DEPRESSION." Journal of Pediatric Gastroenterology and Nutrition 76(Supplement 1): 1227.
	Objectives and Study: Breastfeeding mothers experience postpartum depression (PPD) frequently. Postpartum depression neagitvely affects well-being of infant and decreases diet quality of mother. In this study, we aimed to investigate the effect of Mediterranean diet (MD) on postpartum depression scores of depressive mothers and the growth of the baby. Method(s): Mothers of children under 1 year of age who were admitted for vaccination or well-child visit were screened for PPD with Edinburgh postpartum depression scale (EDPS). 430 mothers were screened and 100 of them had scores >=12 included in the study and randomized into 2 groups. After dropouts, 31 mothers were remained in MD and 29 mothers in the control group finished. Demographic data, EPDS, Multidimensional Scale of Perceived Social Support, physical activity record, 3 days food diary, healthy eating index-2010 and Mediterranean Diet Adherence Scale were used at 1st and 3rd months. Ethical approval was obtained from Istanbul Medipol University Ethics Committee on Non- Interventional Studies. Result(s): Smoking and family history of depression were more common in control group. Other demographic data, social support and physical activity didn't change between groups throughout the study period. In intention-to-treat analysis depression score were significantly lower in the study group in 1st month. At the 3rd month this difference was not apparent. Length-for-age was significantly higher in study group at 3rd month. In per-protocol analysis, depression scores were significantly lower, diet quality was higher in mothers with high adherence to MD group in 1st and 3rd months. Conclusion(s): Adherence to MD decreases PPD scores and increases diet quality in breastfeeding mothers. Mothers should be screened for postpartum depression in pediatrics clinics and multidisciplinary support including dietitian, psychologist/psychiatric for mothers with depression should be provided.

Geetha, K. and R. Elangovan (2022). "EFFECT OF YOGIC PRACTICES ON SELECTED RISK FACTORS AMONG ADOLESCENT GIRLS SUFFERING WITH DYSMENORRHEA." Asian Journal of Microbiology, Biotechnology and Environmental Sciences 24(2): 402-408.
	To achieve the purpose of the random group experimental study, 120 girls suffering with dysmenorrhea were identified, 90 girls among them would be screened and finally, 40 were selected randomly by using a random group sampling method between 18 and 22 years of age. The subjects might be divided into experimental group and control group of 20 subjects each. The Experimental Group was treated with Yogic practices for 12 weeks, Six days a week during the morning. The control group was on active rest. The pre-test and post-test were conducted before and after the training for the experimental and control group and the scores on Body Weight and General Mental Alertness were measured. Analysis of covariance (ANCOVA) was used to find out the significant differences among the groups. The result of the study showed that Body Weight reduced significantly and General Mental Alertness improved as a result of Yogic practices in the Experimental Group. Hence the hypothesis was accepted at a 0.05 level of confidence. The conclusion was that the Yogic practices helped to reduced Body Weight and improve General Mental Alertness among adolescent girls suffering from dysmenorrhea.Copyright © Global Science Publications.

Geldof Nadine, I., et al. (2022). "Hyperbaric oxygen treatment for late radiation-induced tissue toxicity in treated gynaecological cancer patients: a systematic review." Radiation oncology (London, England) 17(1): 164.
	Purpose: The aim of this study was to investigate the result of hyperbaric oxygen therapy (HBOT) in women with treated gynaecological malignancies who suffer from late radiation-induced tissue toxicity (LRITT). Moreover, which symptoms of LRITT benefit most from HBOT was evaluated as well.; Material and Methods: An online literature search was conducted using PubMed; Embase and the Cochrane Library. Studies were included if the study examined gynaecological cancer patients who had been treated with radiotherapy, who suffered from LRITT and who subsequently received HBOT. In addition, the outcome measures were based on examining the effects of HBOT.; Results: Twenty-one articles were included. The study investigating proctitis reported an improvement and three out of four studies investigating cystitis reported decreased complaints in women treated for gynaecological malignancies. In addition, all studies reported improvement in patients with wound complications and fifty percent of the studies reported better Patient Reported Outcome Measurements (PROMS) in women with gynaecological malignancies. Finally, all studies, except one related to pelvic malignancies reported reduced prevalence of symptoms for cystitis and proctitis and all studies reported better PROMS. However, only eleven studies reported p-values, nine of which were significant.; Conclusion: This study demonstrated that HBOT has a positive effect in women with gynaecological LRITT. Within the included patient group, gynaecological cancer patients with wound complications seem to benefit most from this treatment compared to other late side effects of LRITT. (© 2022. The Author(s).)

Gemma, L., et al. (2021). "The effectivity and safety of luteal phase support with progesterone following ovarian stimulation and intra uterine insemination: A systematic review and meta-analysis."
	
GeneMedicine, C. and Ltd (2024). GM103 Intratumoral Injection in Patients With Locally Advanced, Unresectable, Refractory and/or Metastatic Solid Tumors.
	No Results Available Drug: GM103 (Part A)|Drug: GM103 (Part B)|Drug: GM103 and Pembrolizumab (Part C) Percentage of patients with DLTs by cohorts|Percentage of patients with DLTs|Incidence of AEs, AESIs, SAEs, AEs leading to discontinuation, and AEs resulting in death|ORR|DCR defined as the proportion of patients whose BOR was CR, PR and SD|Median PFS defined as the time from the date of the first administration of study drug to the date of disease progression or death|Incidence of GM103 detection|Changes in the level of anti-adenovirus antibodies(ADA) in blood compared to baseline (ADA in genome copies/mL using qPCR) All Phase 1|Phase 2 125 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GM103-CT-101 October 30, 2028

Genentech, I. (2022). A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors.
	No Results Available Drug: RO7502175|Drug: Atezolizumab Phase Ia: Number of Participants with Dose Limiting Toxicities (DLTs)|Phase Ib: Number of Participants with DLTs|Phase Ia: Number of Participants with Treatment Emergent Adverse Events|Phase Ib: Number of Participants with Treatment Emergent Adverse Events|Phase Ia and Phase Ib: Maximum Serum Concentration (Cmax) of RO7502175|Phase Ia and Phase Ib: Objective Response Rate (ORR)|Phase Ia and Phase Ib: Duration of Response (DOR)|Phase Ia and Phase Ib: Progression Free Survival (PFS)|Phase Ia and Phase Ib: Percentage of Participants With Anti-Drug Antibody (ADA) to RO7502175 All Phase 1 365 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GO43860|2021-006708-34 October 31, 2025

Geng, A. (2022). "Observation on the effect of biomimetic electrical stimulation combined with fenmotone on promoting endometrial repair after repeated artificial abortion." Medical Theory and Practice / 医学理论与实践 35(6): 1010‐1012.
	Objective: To investigate the efficacy and safety of biomimetic electrical stimulation therapy combined with sequential oral administration of fenmoxone for repeated induced abortion. Methods: A total of 120 patients who underwent repeated abortion in our hospital from January 2019 to March 2021 were randomly divided into two groups, the control group was given sequential oral administration of fenmeton, and the observation group was additionally treated with biomimetic electrical stimulation; The postoperative rehabilitation indexes and physiological related indexes at 21 days after operation were observed, and the complication rate and adverse reactions were followed up for 6 months. RESULTS: The postoperative abdominal pain duration, vaginal bleeding time, vaginal bleeding volume, menstrual rehydration time and other rehabilitation indicators in the observation group were significantly lower than those in the control group (P<0.05). CONCLUSION: Biomimetic electrical stimulation therapy combined with sequential oral administration of fenmoxone can promote endometrial repair in repeated abortion recipients, speed up the postoperative recovery process, and reduce intrauterine adhesions.

Geng, X., et al. (2022). "Effect of overall nursing combined with acupressure in preventing postpartum urinary retention." American journal of translational research 14(2): 1347-1353.
	OBJECTIVES: This study investigated the effects of overall nursing care combined with acupressure in preventing postpartum urinary retention. METHODS: A total of 200 parturients with vaginal delivery in our hospital from March to October 2019 were enrolled and randomized to a control group and an observation group with 100 cases each. The control group received conventional nursing, while the observation group was also given "overall" nursing combined with acupressure. The two groups were compared in the incidence of urinary retention, time to the first urination, first urine volume, residual urine volume, pelvic floor muscle fiber contraction time, satisfaction, and treatment efficiency. RESULTS: The two groups presented no significant difference in general information (P>0.05). Compared to the control group, the observation group showed a lower incidence of urinary retention and experienced an earlier time to first urination (both P<0.001). A significantly smaller residual urine volume was observed in the observation group as compared to controls at 4 h and 12 h after delivery (P<0.05). The observation group outperformed the control group in terms of pelvic floor muscle fiber contraction duration (P<0.001). Moreover, the observation group showed a treatment efficiency and nursing satisfaction superior to the control group (P<0.05). CONCLUSIONS: Overall nursing care combined with acupressure can exert strong positive effects on the incidence of postpartum urinary retention, time to the first urination, and residual urine volume in parturients with vaginal delivery and improve their satisfaction.

Geng, Z. Y., et al. (2023). "Addition of preoperative transversus abdominis plane block to multimodal analgesia in open gynecological surgery: a randomized controlled trial." BMC anesthesiology 23(1): 21.
	BACKGROUND: Transversus abdominis plane (TAP) block can provide effective analgesia for abdominal surgery. However, it was questionable whether TAP had additional effect in the context of multimodal analgesia (MMA). Therefore, this study aimed to assess the additional analgesic effect of preoperative TAP block when added to MMA protocol in open gynecological surgery. METHODS: In this prospective, randomized‐controlled trial, 64 patients scheduled for open gynecological surgery were randomized to receive preoperative TAP block (Study group, n = 32) or placebo (Control group, n = 32) in addition to MMA protocol comprising dexamethasone, acetaminophen, flurbiprofen and celecoxib, and rescued morphine analgesia. The primary outcome was rescued morphine within 24 h after surgery. Secondary outcomes included pain scores, adverse effects, quality of recovery measured by 40‐item quality of recovery questionnaire score (QoR‐40) at 24 h, and quality of life measured with short‐form health survey (SF ‐ 36) on postoperative day (POD) 30. RESULTS: The Study group had less rescued morphine than the control group within 24 h [5 (2‐9) vs. 8.5 (5‐12.8) mg, P = 0.013]. The Study group had lower pain scores at 1 h [3 (2‐4) vs. 4 (3‐5), P = 0.007], 2 h [3 (2‐4) vs. 3.5 (3‐5), P = 0.010] and 6 h [3 (2‐3) vs. 3 (2.3‐4), P = 0.028], lower incidence of nausea at 48 h (25.8% vs. 50%, P = 0.039), and higher satisfaction score [10 (10‐10) vs. 10 (8‐10), P = 0.041]. The SF‐36 bodily pain score on POD 30 was higher in the Study group (59 ± 13 vs. 49 ± 16, P = 0.023). CONCLUSIONS: Preoperative TAP block had additional analgesic effect for open gynecological surgery when used as part of multimodal analgesia. Rescued morphine within 24 h was significantly reduced and the SF‐36 bodily pain dimension at 30 days after surgery was significantly improved. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2000040343, on Nov 28 2020).

Genmab and S. E. BioNTech (2024). GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer.
	No Results Available Biological: Pembrolizumab|Biological: Acasunlimab Objective Response Rate (ORR)|Duration of Response (DOR)|Time to Response (TTR)|Disease Control Rate (DCR)|Number of Participants with Treatment Emergent Adverse Events (TEAEs) and as Per Severity Female Phase 2 80 Industry Allocation: Non-Randomized|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GCT1046-05|2022-502453-33-00 June 1, 2028

Genovese, F., et al. (2023). "Impact of Hysterotomy Closure Technique on Subsequent Cesarean Scar Defects Formation: A Systematic Review [see note]." Gynecologic and Obstetric Investigation 88(2): 81-90.
	Introduction: The uterine caesarean scar defect, also known as uterine niche or isthmocele, is an irregularity in the anterior uterine wall at the site of a previous cesarean section scar. It is associated with obstetrical complications such as caesarean scar, ectopic pregnancy, uterine rupture, and the placenta accreta spectrum. Women with cesarean scar defects are frequently asymptomatic but may also experience abnormal vaginal bleeding, chronic pelvic pain, and infertility.; Methods: This systematic review aims to determine the best hysterotomy closure technique to prevent subsequent development of uterine scar defects. An electronic search in Medline, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov was performed from January 2001 until December 2020 for studies evaluating hysterotomy closure techniques.; Results: Our systematic search strategy identified 1,781 titles. Six studies fulfilled inclusion criteria and were included in the final analysis. The results supported the superiority of the double-layer closure over the single-layer closure.; Conclusions: Hysterotomy closure with continuous running sutures in two layers represents a suitable option to prevent cesarean scar defect formation. Particularly, the first layer should include the decidua and the second layer should overlap the first. (© 2023 S. Karger AG, Basel.)

Genovese, F., et al. (2023). "Techniques and endocrine-reproductive outcomes of ovarian transposition prior to pelvic radiotherapy in both gynecologic and non-gynecologic cancers: A systematic review and meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.
	Background: Premature ovarian failure may be a consequence of radiotherapy administered for the treatment of various female oncologic diseases. Before radiotherapy, fertility may be preserved through ovarian transposition (OT), which consists of moving the ovaries away from the radiation field.; Objective: To ascertain all types of surgical techniques employed for OT, outline the endocrine and reproductive outcomes of each one, and discover if one works better than the others.; Search Strategy: The authors performed a systematic search of the English literature looking for all studies related to OT before radiotherapy published up to June 2023. Nine studies were included.; Selection Criteria: The eligible studies were assessed based on the presence of a description of the surgical technique employed for OT before pelvic radiotherapy and a report of the endocrine and reproductive outcomes.; Data Collection and Analysis: Odds ratios (OR) with 95% confidence intervals were used to compare endocrine and reproductive outcomes The χ 2 test was employed for the statistical analysis and a P value less than 0.05 was considered significant.; Main Results: A total of 323 female patients aged between 7 and 51 years-198 (61.3%) with non-gynecologic cancer and 125 (38.7%) with gynecologic cancer-underwent OT, either bilateral (221, 68.4%) or unilateral (102, 31.6%), before radiotherapy. Essentially, two types of OT were employed: lateral and medial. A total of 71 (22%) patients underwent medial OT and 252 (78%) patients (127 with non-gynecologic tumors and 125 with gynecologic tumors) had a lateral OT. The latter was used in a similar percentage of cases for gynecologic (50.4%) and non-gynecologic (49.6%) tumors, whereas the medial approach was performed only for non-gynecologic cancers (Hodgkin's lymphoma). The difference between medial OT and lateral OT was not significant regarding the preservation of endocrine function (OR 0.65, P = 0.120). However, midline OT worked better in terms of reproductive outcomes. In fact, the percentage of patients with pregnancy (49.2%) and live births (45%) associated with medial OT was significantly higher than that associated with lateral OT, 6.5% and 13.4%, respectively, and the difference between such data was statistically significant (OR 7.04, P = 0.001 and OR 5.29, P = 0.003, respectively).; Conclusions: Ovarian transposition is an important method to preserve fertility before radiotherapy, considering the worldwide ongoing use of this treatment for various cancers arising in young women. The surgical method depends on the type of disease, but OT-especially medial OT when feasible-is effective in terms of ovarian function preservation and reproductive outcomes. (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Geoffrion, R. and M. Larouche (2021). "Directive clinique no 413: Traitement chirurgical du prolapsus genital apical chez les femmes." Journal of Obstetrics and Gynaecology Canada 43(4): 524-538.e521.
	Objectif: Comparer les taux de reussite et de complications des interventions de suspension apicale pour le traitement du prolapsus symptomatique de l'uterus ou du dome vaginal. Population cible: Les femmes presentant un prolapsus symptomatique de l'uterus ou du dome vaginal qui souhaitent obtenir un traitement chirurgical. Options: Les interventions abordees sont les methodes reconstructives apicales par voie abdominale (colposacropexie, hysterosacropexie ou hysteropexie avec suspension aux ligaments utero-sacres) par chirurgie ouverte, laparoscopique ou robotisee; les methodes reconstructives apicales par voie vaginale (suspension du dome vaginal ou hysteropexie, sacrospinofixation, suspension aux ligaments utero-sacres, suspension au muscle ilio-coccygien, culdoplastie de McCall ou amputation du col [technique de Manchester]); et les interventions vaginales obliterantes (avec ou sans uterus in situ). Les interventions individuelles ou les grandes categories d'interventions ont ete comparees: (1) reconstruction par voie vaginale versus abdominale, (2) interventions reconstructives par voie abdominale, (3) interventions reconstructives par voie vaginale, (4) reconstruction par hysterectomie avec suspension par comparaison a la reconstruction par hysteropexie et (5) options reconstructives versus obliterantes. Resultats: Le comite d'urogynecologie a selectionne les resultats cliniques suivants: echec objectif (obtenu par des systemes valides de quantification du prolapsus genital et defini comme un echec global objectif et un taux d'echec par compartiment); echec subjectif (reapparition de la sensation de protuberance determinee subjectivement, avec ou sans l'utilisation d'un questionnaire valide); reoperation pour un prolapsus genital recidive; complications postoperatoires de troubles mictionnels (incontinence urinaire d'effort de novo ou postoperatoire; reoperation d'une incontinence urinaire d'effort de novo, persistante ou recidivee; incontinence urinaire par urgenturie; et dysfonction mictionnelle); lesion des voies urinaires detectee en perioperatoire (vessie ou uretere); autres complications (exposition prothetique, definie comme un treillis visible et expose dans le vagin et une douleur pelvienne non sexuelle); et fonction sexuelle (dyspareunie de novo et score de la fonction sexuelle d'apres un questionnaire valide). Benefices, risques et couts: Cette directive clinique sera benefique pour les patientes qui souhaitent obtenir une correction chirurgicale du prolapsus genital apical en ameliorant les conseils sur les options de traitement chirurgical et les resultats cliniques possibles. La directive sera egalement utile pour les fournisseurs de soins chirurgicaux en ameliorant leurs connaissances sur diverses methodes chirurgicales. Les donnees presentees pourraient servir a elaborer des cadres et des outils pour la prise de decision partagee. Donnees probantes: Nous avons effectue des recherches dans les bases de donnees Medline, Cochrane Central Register of Controlled Trials (CENTRAL) et Embase pour des articles publies entre 2002 et 2019. Les termes de recherche etaient nombreux et portaient sur les interventions de correction du prolapsus genital apical, les voies d'abord et les complications. Nous avons exclu les reconstructions par treillis transvaginal et les etudes comparant les interventions sans suspension apicale. Nous avons inclus des essais cliniques randomises et des etudes comparatives prospectives ou retrospectives. Nous avons limite nos recherches aux articles publies en anglais ou en francais dont le texte integral etait accessible. Une revue systematique des articles avec meta-analyse a ensuite ete effectuee. Methodes de validation: Les auteures ont evalue la qualite des donnees probantes et la force des recommandations en utilisant lecadre methodologique d'evaluation, de developpement et d'evaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les definitions et tableau A2 pour l'interpretation des recommandations fortes et faibles). Professionnels cibles: Gynecologues, urologues urogynecologues et autres fournisseurs de soins de sante qui evaluent, conseillent et soignent des femmes ayant un prolapsus genital. DECLARATIONS SOMMAIRES: Toutes les declarations font reference a la correction du prolapsus genital apical a court et a moyen terme (jusqu'a 5 ans), sauf indication contraire. 1 La suspension vaginale par suture a divers ligaments pelviens etait inferieure a la colposacropexie par voie abdominale (toutes voies d'abord confondues) avec treillis synthetique pour ce qui est des resultats cliniques suivants: * echec global objectif (moyenne); * echec apical objectif (moyenne). 2 La suspension vaginale par suture a divers ligaments pelviens etait comparable a la colposacropexie par voie abdominale (toutes voies d'abord confondues) avec treillis synthetique pour ce qui est des resultats cliniques suivants: * echec anterieur objectif (moyenne); * echec posterieur objectif (moyenne); * sensation subjective d'un prolapsus genital recidive (moyenne); * reoperation pour un prolapsus genital recidive (moyenne); * lesions vesicales et ureterales peroperatoires (faible); * troubles mictionnels postoperatoires (faible). 3 La suspension vaginale par suture a divers ligaments pelviens n'etait pas associee au risque d'exposition du treillis comparativement a la colposacropexie abdominale (toutes voies d'abord confondues) avec treillis synthetique, qui est associee a un risque d'exposition du treillis de 2,7 % a 3,4 % (moyenne). 4 La colposacropexie par voie abdominale ouverte etait inferieure a la colposacropexie minimalement invasive (laparoscopique ou robotisee) pour ce qui est des resultats cliniques suivants: * echec global objectif (faible); * echec posterieur objectif (faible). 5 La colposacropexie par voie abdominale ouverte etait comparable a la colposacropexie minimalement invasive (laparoscopique ou robotisee) pour ce qui est des resultats cliniques suivants: * echec objectif anterieur (faible); * sensation subjective d'un prolapsus genital recidive (moyenne); * reoperation pour un prolapsus genital recidive (moyenne); * lesions vesicales peroperatoires (moyenne); * reoperation pour incontinence urinaire d'effort (faible); * exposition du treillis (moyenne). 6 Les diverses voies d'abord minimalement invasives de la colposacropexie (laparoscopique ou robotisee) se sont revelees comparables pour ce qui est des risques suivants: * sensation subjective d'un prolapsus genital recidive (tres faible); * lesions vesicales peroperatoires (moyenne); * incontinence urinaire d'effort postoperatoire (tres faible); * exposition du treillis (moyenne). 7 Il n'y a pas suffisamment de donnees comparant l'incontinence urinaire par urgenturie et le risque de dysfonction mictionnelle apres une colposacropexie par voie abdominale ouverte et minimalement invasive ni entre les differentes methodes de colposacropexie minimalement invasive (tres faible). 8 La suspension aux ligaments utero-sacres et la sacrospinofixation se sont revelees comparables pour ce qui est des risques suivants: * taux d'echec objectif (global et par compartiment) (moyenne); * sensation subjective d'un prolapsus genital recidive (moyenne); * reoperation pour un prolapsus genital recidive (moyenne); * lesions vesicales peroperatoires (moyenne); * reoperation pour incontinence urinaire d'effort (faible). 9 La suspension aux ligaments utero-sacres s'est revelee avoir un risque plus eleve comparativement a la sacrospinofixation pour ce qui est du risque suivant: * lesions ureterales peroperatoires (moyenne). 10 L'hysterectomie avec suspension etait comparable a l'hysteropexie (toutes voies d'abord confondues) pour ce qui est des resultats cliniques suivants: * echec global objectif (faible); * echec anterieur objectif (faible); * echec apical objectif (faible); * sensation subjective d'un prolapsus genital recidive (faible); * reoperation pour un prolapsus genital recidive (faible); * troubles mictionnels (faible); * lesions vesicales et ureterales peroperatoires (faible). 11 L'hysterectomie avec suspension s'est revelee inferieure a l'hysteropexie (t tes voies d'abord confondues) pour ce qui est du resultat clinique suivant: * echec posterieur objectif (faible). 12 L'hysterectomie avec colposacropexie s'est revelee avoir un risque superieur comparativement a l'hysterosacropexie (par voie abdominale, laparoscopique ou robotisee) pour ce qui est du risque suivant: * exposition du treillis (faible). 13 L'hysterectomie vaginale avec suspension et l'hysteropexie par voie vaginale se sont montrees comparables pour ce qui est des risques suivants: * echec objectif (global et par compartiment) (faible); * reoperation pour un prolapsus genital recidive (tres faible); * lesions ureterales peroperatoires (tres faible). 14 A court terme (1 an), la correction du prolapsus apical de stade avance (stade 3 ou 4) au moyen de la suspension vaginale par suture a divers ligaments pelviens est comparable au colpocleisis pour ce qui est des resultats cliniques d'echec global objectif, de lesions peroperatoires des voies urinaires et d'amelioration specifique de la qualite de vie (tres faible). 15 La suspension aux ligaments utero-sacres s'est revelee avoir un risque plus faible comparativement a la sacrospinofixation pour ce qui est du risque suivant: * douleur aux fesses transitoire ou a court terme (faible). 16 Les donnees actuelles ne sont pas concluantes pour ce qui est des resultats cliniques relatifs a la douleur pelvienne persistante ou a la fonction sexuelle postoperatoire, notamment la dyspareunie de novo, lorsque l'on compare la suspension apicale par voie vaginale par rapport a la voie abdominale, la suspension apicale minimalement invasive a la voie ouverte, les differentes methodes de suspension apicale du dome vaginal entre elles et l'hysterectomie avec suspension par rapport a l'hysteropexie (tres faible). RECOMMANDATIONS: 1 Il y a lieu d'informer les femmes souhaitant obtenir une correction chirurgicale pour un prolapsus apical que la suspension vaginale par suture, par comparaison a la colposacropexie par voie abdominale (toutes voies d'abord confondues), presente un risque accru d'echec objectif, mais un taux comparable pour ce qui est (1) de l'echec subjectif, (2) de la reoperation pour un prolapsus genital recidive et (3) des complications. Il importe donc de prendre ces risques en compte au regard du risque permanent d'exposition du treillis apres une colposacropexie, complication qui peut exiger une reoperation (conditionnelle, moyenne). 2 Il est recommande pour les chirurgiens dument formes de privilegier la colposacropexie minimalement invasive par voie laparoscopique ou robotisee (si l'equipement chirurgical est disponible), plutot que la colposacropexie par chirurgie ouverte, etant donne l'amelioration objective globale des resultats cliniques et l'equivalence des resultats cliniques subjectifs a court et a moyen terme (conditionnelle, faible). 3 Il est possible d'offrir la suspension vaginale aux ligaments utero-sacres et la sacrospinofixation aux femmes ayant un prolapsus genital apical en fonction des preferences du chirurgien et de la patiente. Les deux methodes semblent avoir des resultats cliniques objectifs et subjectifs comparables jusqu'a 5 ans post-intervention, a l'exception d'une augmentation du risque de lesion ureterale peroperatoire dans le cas de la suspension aux ligaments utero-sacres et du risque de douleur aux fesses transitoire ou a court terme apres une sacrospinofixation (forte, moderee). 4 Il est possible d'offrir differentes voies d'abord et techniques d'hysteropexie comme solution de rechange a l'hysterectomie et a la suspension pour les femmes atteintes d'un prolapsus genital apical qui souhaitent preserver leur uterus; ces techniques et voies d'abord sont associees a des resultats cliniques objectifs et subjectifs comparables pour les 5 premieres annees post-intervention (conditionnelle, faible). 5 En depit du manque de donnees probantes comparatives, il y a lieu d'aborder le colpocleisis comme option therapeutique avec les femmes qui ne souhaitent plus etre sexuellement actives; il semble s'agir d'une intervention reussie pour laquel on signale peu de complications (fortes, faibles). 6 Il y a lieu d'informer les femmes qui se soumettent au traitement chirurgical du prolapsus apical symptomatique qu'il existe peu de donnees comparatives sur la douleur pelvienne et la fonction sexuelle postoperatoires pour diverses interventions. Dans l'ensemble, le risque de douleur pelvienne postoperatoire semble faible, et la fonction sexuelle semble s'ameliorer chez les femmes sexuellement actives qui se soumettent au traitement chirurgical reconstructif du prolapsus genital apical (conditionnelle, tres faible).Copyright © 2021

Geoffrion, R. and M. Larouche (2021). "Guideline No. 413: Surgical Management of Apical Pelvic Organ Prolapse in Women." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 43(4): 511.
	Objective: To compare success and complication rates of apical suspension procedures for the surgical management of symptomatic uterine or vaginal vault prolapse.; Target Population: Women with symptomatic uterine or vaginal vault prolapse seeking surgical correction.; Options: Interventions included abdominal apical reconstructive repairs (sacrocolpopexy, sacrohysteropexy, or uterosacral hysteropexy) via open, laparoscopic, or robotic approaches; vaginal apical reconstructive repairs (vault suspensions or hysteropexy, sacrospinous, uterosacral, iliococcygeus, McCall's, or Manchester types); and vaginal obliterative procedures (with or without uterus in situ). Individual procedures or broad categories of procedures were compared: (1) vaginal versus abdominal routes for reconstruction, (2) abdominal procedures for reconstruction, (3) vaginal procedures for reconstruction, (4) hysterectomy and suspension versus hysteropexy for reconstruction, and (5) reconstructive versus obliterative options.; Outcomes: The Urogynaecology Committee selected outcomes of interest: objective failure (obtained via validated pelvic organ prolapse [POP] quantification systems and defined as overall objective failure as well as failure rate by compartment); subjective failure (recurrence of bulge symptoms determined subjectively, with or without use of a validated questionnaire); reoperation for POP recurrence; complications of postoperative lower urinary tract symptoms (de novo or postoperative stress urinary incontinence; reoperation for persistent, recurrent, or de novo stress urinary incontinence; urge urinary incontinence; and voiding dysfunction); perioperatively recognized urinary tract injury (bladder or ureter); other complications (mesh exposure, defined as mesh being visible and exposed in the vagina, and non-sexual pelvic pain); and sexual function (de novo dyspareunia and sexual function score according to a validated questionnaire).; Benefits, Harms, and Costs: This guideline will benefit patients seeking surgical correction of apical POP by improving counselling on surgical treatment options and possible outcomes. It will also benefit surgical providers by improving their knowledge of various surgical approaches. Data presented could be used to develop frameworks and tools for shared decision-making.; Evidence: We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from 2002 to 2019. The search included multiple terms for apical POP surgical procedures, approaches, and complications. We excluded POP repairs using transvaginal mesh and studies that compared procedures without apical suspension. We included randomized controlled trials and prospective or retrospective comparative studies. We limited language of publication to English and French and accessibility to full text. A systematic review and meta-analysis was performed.; Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).; Intended Users: Gynaecologists, urologists, urogynaecologists, and other health care providers who assess, counsel, and care for women with POP.; Summary Statements: All statements refer to correction of apical vaginal prolapse in the short and medium term (up to 5 years), except when otherwise specified. (Copyright © 2021. Published by Elsevier Inc.)

Gerbasi, M. E., et al. (2021). "Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making." Journal of women's health (2002) 30(3): 385-392.
	Background: Brexanolone (BRX) injection was approved by the United States Food and Drug Administration in 2019 for the treatment of adults with postpartum depression (PPD) based on two Phase 3 clinical trials. Materials and Methods: Data from the three trials were combined. PPD-specific 17-item Hamilton Rating Scale for Depression (HAMD-17) group-level minimal important difference (MID) and patient-level meaningful change (meaningful change threshold [MCT]) were estimated and applied to differences in BRX versus placebo (PBO) at hour 60 (primary endpoint) and day 30 (end of trial follow-up). Likelihood of HAMD-17 response and remission and Clinical Global Impression of Improvement (CGI-I) response for BRX versus PBO were assessed at hour 60 and as sustained through day 30 using relative risk. Associated number needed to treat (NNT) and number needed to harm (NNH) values were also estimated. Results: Two-hundred nine patients were included. The average HAMD-17 MID estimate was -2.1; the least-squared mean difference between BRX and PBO exceeded this at hour 60 and day 30. Minimal, moderate, and large MCTs were estimated to be -9, -15, and -20 points, respectively. Significantly more BRX-treated than PBO-treated patients achieved minimal, moderate, and large change (all ps < 0.05) at hour 60 and large meaningful response at day 30 (p < 0.05). BRX-treated patients were more likely to sustain HAMD-17 remission and CGI-I response through day 30 versus PBO. NNTs ranged from 4 to 8, with NNH of 97. Conclusions: BRX provided meaningful changes relative to PBO, rapid (hour 60), and sustained improvements (day 30) in PPD symptoms, low NNT, and large NNH. These results may help inform treatment decision-making. Clinicaltrials.gov registration numbers: NCT02614547, NCT02942004, and NCT02942017.

Gerber, E., et al. (2022). "Predicting chemoresponsiveness in epithelial ovarian cancer patients using circulating small extracellular vesicle-derived plasma gelsolin." MedRxiv.
	Background: Resistance to chemotherapy continues to be a challenge when treating epithelial ovarian cancer (EOC), contributing to low patient survival rates. While CA125, the conventional EOC biomarker, has been useful in monitoring patients' response to therapy, there are no biomarkers used to predict treatment response prior to chemotherapy. Previous work in vitro showed that plasma gelsolin (pGSN) is highly expressed in chemoresistant EOC cell lines, where it is secreted in small extracellular vesicles (sEVs). Whether sEVs from tumour cells are secreted into the circulation of EOC patients and could be used to predict patient chemoresponsiveness is yet to be determined. This study aims to determine if sEV-pGSN in the circulation could be a predictive biomarker for chemoresistance in EOC. Method(s): Sandwich ELISA was used to measure pGSN concentrations from plasma samples of 96 EOC patients (primarily high grade serous EOC). sEVs were isolated using ExoQuick ULTRA and characterized using western blot, nanoparticle tracking analysis, and electron microscopy after which pGSN was measured from the sEVs. Patients were stratified as platinum sensitive or resistant groups based on first progression free interval (PFI) of 6 or 12 months. Result(s): Total circulating pGSN was significantly decreased and sEV-pGSN increased in patients with a PFI <= 12 months (chemoresistant) compared to those with a PFI > 12 months (chemosensitive). The ratio of total pGSN to sEV-pGSN further differentiated these groups and was a strong predictive marker for chemoresistance (sensitivity: 73.91%, specificity: 72.46%). Predetermined CA125 was not different between chemosensitive and chemoresistant groups and was not predictive of chemoresponsiveness prior to treatment. When CA125 was combined with the ratio of total pGSN/sEV-pGSN, it was a significant predictor of chemoresponsiveness, but the test performance was not as robust as the total pGSN/sEV-pGSN alone. Conclusion(s): Total pGSN/sEV-pGSN was the best predictor of chemoresponsiveness prior to treatment, outperforming the individual biomarkers (CA125, total pGSN, and sEV-pGSN). This multianalyte predictor of chemoresponsiveness could help to inform physicians' treatment and follow up plan at the time of EOC diagnosis, thus improving patients' outcomes.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Gerkowicz, A., et al. (2021). "Photodynamic Therapy in the Treatment of Vulvar Lichen Sclerosus: A Systematic Review of the Literature." Journal of Clinical Medicine 10(23).
	Vulvar lichen sclerosus (VLS) is a chronic inflammatory disease involving the genital skin and mucous membrane. Patients exhibit focal atrophy and destructive scarring, with an increased risk of malignant transformation. Due to objective symptoms as well as subjective complaints, patients with VLS experience emotional distress, lowered mood, and sexual dysfunction, which is reflected in impaired health-related quality of life. Thus, the necessity of implementing appropriate therapy at the earliest possible stage of the disease in order to avoid serious complications is highlighted. We presented the systematic review of available literature, performed with MEDLINE, Cinahl, Central, Scopus, and Web of Science databases. We identified a total of twenty relevant studies which indicate that photodynamic therapy (PDT) is a valuable therapeutic modality in the treatment of VLS.

Gerontakos, S., et al. (2023). "Feasibility and efficacy of implementing group visits for women's health conditions: a systematic review." BMC Health Services Research 23(1): 549.
	Background: Shared medical appointments, also known as group visits, are a feasible and well-accepted approach for women receiving antenatal care, yet the feasibility and efficacy of this approach for female-specific reproductive conditions is uncertain.; Objective: The aim of this systematic review was to (a) determine the feasibility of group visits in adults with any female-specific reproductive condition, and (b) identify whether delivering group care for these conditions impacts clinical outcomes.; Method: Six databases and two clinical trials registries were searched from inception through to 26 January 2022 for original research examining group medical visits or group consultation interventions for adults with female reproductive conditions or pathologic conditions specific to the female reproductive system.; Results: The search yielded 2584 studies, of which four met the inclusion criteria. Included studies sampled women with breast cancer, chronic pelvic pain, polycystic ovary syndrome and gynaecological cancers. Studies reported high levels of patient satisfaction, with participants indicating their expectations had been met or exceeded. The impact of group visits on clinical outcomes was inconclusive however.; Discussion/conclusions: The studies in this review indicate delivery of female-specific healthcare via a group model maybe feasible and well-accepted. The review provides a solid basis for proposing larger and longer studies on group visits for female reproductive conditions.; Trial Registration: The review protocol was registered with PROSPERO (CRD42020196995). (© 2023. The Author(s).)

Gerosa, D., et al. (2022). "Application of Honey to Reduce Perineal Laceration Pain during the Postpartum Period: A Randomized Controlled Trial." Healthcare (Basel, Switzerland) 10(8).
	Perineal lacerations affect between 35 and 85% of women during childbirth and may be responsible for postpartum pain. Honey has been demonstrated to have interesting properties that can promote wound healing. The aim was to evaluate the effectiveness of the application of honey to the perineum to reduce perineal pain during the early postpartum period. A randomized controlled trial including 68 women was conducted. In the intervention group, honey was applied to perineal lacerations for four days, in addition to standard care. The control group received only standard care. The primary outcome was pain intensity using the Visual Analog Scale and pain perception using the McGill Pain Questionnaire (QDSA). The secondary outcomes were a burning sensation, the use of a pain killer, and the women's satisfaction with the honey application. The intensity of pain was not significantly different between the groups on Day 1 (VAS 3.38 in the control group versus 3.34 in the intervention group, p = 0.65) or on Day 4 (VAS 2.28 versus 1.41, respectively, p = 0.09). There was no significant difference regarding the perception of pain with the QDSA. Despite this, most of the women in the intervention group (93%) were satisfied or very satisfied with the use of honey on their perineum.

Gershenson David, M., et al. (2022). "Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial." Lancet (London, England) 399(10324): 541-553.
	Background: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma.; Methods: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m 2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m 2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m 2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting.; Findings: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths.; Interpretation: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma.; Funding: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis.; Competing Interests: Declaration of interests DMG reports payments made to his institution from the National Cancer Institute (NRG Oncology), Novartis, and the GOG Foundation for this study; royalties or licenses from Elsevier and UpToDate outside the submitted work; consulting fees from Genentech outside the submitted work; personal fees for service as a member of the Committee of the National Cancer Institute outside the submitted work; and stock or stock options from Johnson & Johnson, Bristol Myers Squibb, and Biogen outside the submitted work. AM reports service as a masked study statistician for VBL Therapeutics; provision of statistical institutional support for Advaxis; service as a data safety monitoring board reporting statistician for Regeneron; and service on a study steering committee for Genentech and A traZeneca, all outside the submitted work. RLC reports consulting fees from AstraZeneca, Merck–GlaxoSmithKline, and Clovis; grants from Genmab, Genentech–Roche, Janssen, Agenus, Regeneron, and OncoQuest; payments or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from AstraZeneca, Merck–GlaxoSmithKline, and Clovis; and service on a data safety monitoring board or an advisory board for Janssen, VBL Therapeutics, and AstraZeneca, all outside the submitted work. KNM reports service on advisory boards for Alkemeres, AstraZeneca, Aravive, Blueprint Medicines, Eisai, Elevar, GlaxoSmithKline–Tesaro, Genentech–Roche, Hengrui, Immunogen, IMab, Merck, Mereo, Mersana, Myriad, OncXerna, Onconova, Novartis, Sorrento, Tarveda, and VBL Therapeutics, all outside the submitted work; grant funding from PTC Therapeutics, Lilly, Merck, and Genentech–Roche outside the submitted work; funding paid to her institution from Cyteir, Immunocore, Bolt Bio, Amgen, Artios, GlaxoSmithKline–Tesaro, Mereo, Regeneron, Aravive, Verastem, and AstraZeneca, for all of which she also serves as a local principal investigator; serving as national principal investigator for the IMaGYN050 trial of ovarian cancer (Genentech–Roche), the MIRASOL trial of ovarian cancer (Immunogen), the Relevare study of ovarian cancer (OncXerna), the FIRST study of ovarian cancer (GlaxoSmithKline–Tesaro), and the ETCTN 10422 study of ovarian cancer (National Cancer Institute); being the associate director for GOG Partners, on the GOG Foundation board of directors, and the NRG Oncology chair of the ovarian cancer committee; and receiving speaking reimbursement from PER, Research to Practice, Medscape, Great Debates and Updates, and Gyn Mal, all of which are outside the scope of this work but were active during the conduct of this study. SB reports grants paid to their institution from AstraZeneca, Tesaro, and GlaxoSmithKline; personal fees for participation in advisory boards from Amgen, AstraZeneca, Genmab, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Merck Serono, Mersana, Oncxerna, Seagen, Shattuck Lab, and Epsilogen; and personal fees for lectures from Amgen, AstraZeneca, Clovis, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Mersana, Pfizer, Roche, and Takeda, all outside the submitted work. AAS reports a National Cancer Trial Network grant; grants paid to her institution from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Clovis, Eisai, Immutep, Merck, OncoQuest, PharmaMar, Genentech–Roche, Seagen, Tesaro–GlaxoSmithKline, and VBL Therapeutics; consulting fees from Aravive, AstraZeneca, Clovis, Cordgenics, Eisai, Merck, Mersana, Myriad, Oncoquest, Genentech–Roche, and Tesaro–GlaxoSmithKline; presentations for educational events on cervical cancer sponsored by Research to Practice; service on advisory boards (uncompensated) for AbbVie and Regeneron; service on clinical trial steering committees (all uncompensated) for the AtTEnd trial (Hoffman-LaRoche), the Oval Trial (VBL Therapeutics), and the FLORA-5 trial (Oncoquest); and service on the GOG Foundation Board of Directors, the Society of Gynecologic Oncology Board of Directors, and the American Association of Obstetricians and Gynecologists Foundation Board of Trustees, all outside the submitted work. DMO reports National Cancer Institute support for this clinical trial; research funding paid to their institution from AstraZeneca, Tesaro–GlaxoSmithKline, Immunogen, Janssen–Johnson & Johnson, AbbVie Regeneron, Amgen, Novocure, Genentech–Roche, VentiRx Array Biopharma EMD Serono, Ergomed, Ajinomoto, Ludwig Cancer Research Stemcentrx, Cerulean Pharma, the GOG Foundation, the National Cancer Institute, Bristol Myers Squibb, C Serono, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, inVentiv Health Clinical, Iovance Biotherapeutics, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, and Clovis; personal fees for consulting or advisory board membership, or both, from AstraZeneca, Tesaro–GlaxoSmithKline, Immuno en, Ambry, Janssen–Johnson & Johnson, BBI, Agenus, AbbVie, Regeneron, Amgen, Novocure, Genentech–Roche, GOG Foundation, Iovance Biotherapeutics, Myriad Genetics, Eisai, Agenus, Tarveda, Merck, SeaGen, Novartis, Mersana, Clovis, Rubius, and Elevar, all outside the submitted work. OD reports grants or contracts from AstraZeneca, Clovis, Genentech, AbbVie, IMV, Millenium, and Pharmamar; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Tesaro–GlaxoSmithKline and AstraZeneca; payment for expert testimony in one legal case unrelated to the current study; and participation on a data safety monitoring board or advisory board for Merck, Clovis, PACT, and Genentech, all outside the submitted work. SG reports financial support paid to her institution for the present study from the National Clinical Trials Network; grants or contracts from AstraZeneca, AbbVie, Pfizer, Rigel, Iovance, Tesaro, Genentech–Roche, PharmaMar, and GlaxoSmithKline; patents licensed to Sermonix (US patent numbers 10,905,659 and 10,258,604); participation on a data safety monitoring board or advisory board for Sermonix, Elevar Therapeutics, and GlaxoSmithKline; and service as an NRG Oncology phase 1 subcommittee co-chair, all outside the submitted work. BS reports personal fees for service on advisory boards for Abbvie, AstraZeneca, Bostongene, Clovis, Eisai, Genentech, GlaxoSmithKline, Jazz Pharmaceticals, Lilly, Merck, Myriad, Novartis, Nuvation, Onconova, and Seagen; and consulting for the GOG Foundation, all outside the submitted work. AE reports grants or contracts from UKRI for a post-doctoral fellowship outside the submitted work. CG reports grants from GlaxoSmithKline and Novartis for this study (trametinib, the test drug, was sold by GlaxoSmithKline to Novartis during the course of the study). WEB, JP, KCa, WR, DM, KCo, HG, PH, JF, MC, RLH, CSH, HQH, and LW declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Gerstl, B., et al. (2019). "Reproductive outcomes following a stem cell transplant for a haematological malignancy in female cancer survivors: a systematic review and meta-analysis." Supportive Care in Cancer 27(12): 4451-4460.
	Purpose: The use of high-dose chemotherapy and radiotherapy combined with haematopoietic stem cell transplantation (HSCT) may negatively affect a woman's reproductive potential. Reproductive outcomes such as infertility are a major concern for women who undergo treatment for a haematological cancer diagnosis. Objective(s): This systematic review and meta-analysis explores reproductive outcomes following a haematological cancer requiring HSCT. Method(s): Electronic databases were searched to identify studies that reported on reproductive outcomes after treatment for a haematological cancer diagnosis. Studies were included that reported on pregnancy and reproductive outcomes following HSCT for a haematological malignancy. Result(s): The meta-analysis included 14 studies, collectively involving 744 female patients. The subgroup analysis showed an overall pooled estimated pregnancy rate, for autologous or allogeneic HSCT recipients, of 22.7% (n = 438). There were 25% (n = 240) of women who became pregnant after autologous HSCT compared with 22% (n = 198) who subsequently became pregnant following allogeneic HSCT. Conclusion(s): This meta-analysis reflects low pregnancy rates for cancer survivors desiring a family. However, live births are improving over time with new technology and novel therapies. Hence, female cancer patients should be offered timely discussions, counselling and education around fertility preservation options prior to starting treatment with gonadotoxic therapy.Copyright © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Getaneh, F., et al. (2023). "ONABOTULINUM TOXIN A VERSUS SACRAL NEUROMODULATION FOR TREATMENT OF NOCTURIA IN WOMEN WITH REFRACTORY URGE URINARY INCONTINENCE." Neurourology and Urodynamics 42(Supplement 1): S201-S202.
	Introduction: To compare the effect of onabotulinum toxin A versus sacral neuromodulation on nocturia episodes in women with refractory urge urinary incontinence. Method(s): This is a secondary analysis of data prospectively collected in the ROSETTA trial, a multicenter randomized controlled trial comparing the effectiveness of onabotulinum toxin A (BTX) versus sacral neuromodulation (SNM) for women with refractory urge urinary incontinence (UUI). Data was obtained from the National Institute of Health Data and Specimen Hub (DASH) database. Only subjects who reported >= 2 nocturia episodes on average over 3-day diary at baseline were included and divided into two cohorts by treatment: BTX versus SNM. The primary outcome (nocturia episodes per night based on a 3-day bladder diary) was compared between cohorts at baseline, 3 months, 6 months and 9 months post-treatment. A sub- analysis was performed on only treatment Responders (defined as subjects with >= 50% improvement in mean number of UUI episodes/day on 3-day diary). Baseline demographic and clinical characteristics were compared between treatment groups with unpaired t-tests for continuous and contingency table analysis for categorical variables. Change in episodes/day from baseline to 9 months was assessed by mixed effects models for repeated measures data. Comparison of BOTOX and SNM groups at each time point was analyzed by unpaired t-tests with no adjustment for multiple testing. No adjustment of p values was made for multiple testing. Result(s): A total of 119 subjects were included with 64 (54%) undergoing BTX and 55 (46%) undergoing SNM. 116 (97%) subjects were 'Responders' with 62 (53%) BTX and 54 (47%) SNM. There were no significant differences in demographics between groups (p >= 0.05 for all). For the 'Responders', there was a significant decrease in mean nocturia episodes per night after treatment for up to 9 months posttreatment (36.7% decrease in BTX, 33% decrease in SNM, p <= 0.001) with no significant treatment difference between BTX vs SNM. There was a total of 32 patients who had resolution of nocturia (defined as <= 1 mean nocturia episode on 3-day diary) with 18 (56%) undergoing BTX and 14 (44%) undergoing SNM. Conclusion(s): For women with refractory UUI and >= 2 nocturia episodes per night at baseline, treatment with BTX or SNM are associated with a decrease in nocturia episodes over a 9-month follow-up period. Women with UUI and bothersome nocturia can be reassured that BTX and SNM are reasonable options for treatment..

Gezer, Ş., et al. (2021). "Application of thrombin gel matrix for the prevention of lymphocele in patients with endometrial cancer: A prospective randomized trial." Journal of Gynecology Obstetrics and Human Reproduction 50(7): 101994.
	OBJECTIVE: To evaluate a thrombin gel matrix (TGM), Floseal, for the prevention of lymphocele in patients with endometrial cancer who underwent pelvic lymphadenectomy. METHODS: A total of 79 consecutive patients with endometrial cancer were randomly allocated to one of two groups: the TGM group and control group. After completion of the lymphadenectomy, 5 mL of Floseal was applied to the bilateral pelvic sidewalls, especially the femoral canal, obturator, and common iliac vessels areas. Computed tomography scans were obtained for lymphocele evaluation 2 months after the surgery. RESULTS: Three patients from the TGM group, and four patients from the control group were lost during follow-up, and data from 36 participants from each group were analyzed. As the primary outcome, lymphocele developed in 12 patients in both groups (33 %). There was no significant difference between the groups in terms of lymphocele and symptomatic lymphocele development. Lymphocele localization was also not different between the two groups, but the diameter of the lymphoceles detected in the TGM group was significantly greater (p = 0.021). The mean drainage days was significantly shorter in the TGM group (p = 0.015). The amount of drainage was also less in the TGM group, but the difference was not statistically significant. CONCLUSION: Thrombin gel matrix applied to the pelvic sidewalls does not reduce the incidence of symptomatic or asymptomatic lymphoceles after pelvic lymphadenectomy in endometrial cancer. However, it can reduce the amount of drainage and the number of drainage days so it can help to shorten hospitalization.

Gezici, S. and N. Sekeroglu (2019). "Current perspectives in the application of medicinal plants against cancer: Novel therapeutic agents." Anti-Cancer Agents in Medicinal Chemistry 19(1): 101-111.
	Background: Cancer is a disease characterized by uncontrolled cell growth and proliferation. It has become a major health problem in the past decades and is now the second leading cause of death globally. Although, there are different types of treatment such as chemotherapy, immune therapy, radiation, hormone therapy and targeted therapy used against cancer, they have possible side effects and significant deficiencies. Method(s): This review aims to outline the benefits of medicinal plants and plant-derived products and highlight why they should be used as novel anti-cancer therapeutics. Electronic databases, including PubMed, Scopus, ScienceDirect, Cochrane library, and MedlinePlus were searched to summarize in vitro, in vivo and clinical studies on anticancer effects of medicinal plants and their bioactive compounds up-to-date. Result(s): In recent years, a number of medicinal plants have been administered to cancer patients in order to prevent and treat cancer as an alternative therapy. These plants were used because of their rich anticarcinogenic and chemoprotective potentials. In addition to these remarkable properties, these plants have less toxic anticancer, anti-tumor and anti-proliferation agents than traditional therapeutics. Nevertheless, only a small number of natural anti-tumor products including vinblastine, vincristine, podophyllotoxin, paclitaxel (Taxol) and camptothecin have been tested clinically, while vinflunine ditartrate, anhydrovinblastine, NK-611, tafluposide, paclitaxel poliglumex, combretastatins, salvicine, curcumin, indirubin, triptolide, homoharringtonine are still on trial. Conclusion(s): Consequently, more effective anticancer compounds are identified during the clinical trials; these natural products could be a key source of antitumor agents in modern anticancer therapy. It is expected that novel anticancer phytopharmaceuticals produced from medicinal plants could be effectively used in prevention and therapy for the cancers.Copyright © 2019 Bentham Science Publishers.

gGmb, H. E. K. K. W. and o. Cologne University (2024). Biological Mesh Versus Synthetic Mesh in Interdisciplinary RRP With SCP.
	No Results Available Device: interdisciplinary mesh sacro colpopexy with resection rectopexy safety of the experimental internvention as measured by surgical outcome|Altomare Score for Obstruct4ed defecation syndrome (ODS)|Pelvic organ prolapse Quantification (POP Q)|Rectal Toxicity Score for bowel dysfunction|Wexner Incontinence Score for fecal incontinence Female Not Applicable 28 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Outcomes Assessor)|Primary Purpose: Treatment EVKKoeln_BioSynIRS May 31, 2026

Ghafarzadeh, M., et al. (2021). "The role of anti-proliferative effects of atorvastatin on uterine fibroids: findings from a clinical study." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(8): 721-724.
	AIM: Uterine myomas/fibroids are one of the most common benign tumors of the reproductive system in women. Given pleiotropic effects of statins, the aim of this study is to evaluate the therapeutic effects of atorvastatin on uterine fibroids in women of reproductive age. MATERIALS AND METHODS: This randomized clinical study included 90 women aged 35-45 years with uterine fibroids. The patients were randomly allocated into the intervention group (received one tablet, 20 mg of atorvastatin every day for three months) and placebo. Ultrasound was performed every month, and the change in the size of fibroids was recorded for each patient. At the end of the study, the data obtained were analyzed using SPSSv22 and a p value < .05 was considered statistically significant. RESULTS: The mean age in the placebo and intervention group was 39.63 ± 36.3 and 40.35 ± 3.32 years, respectively. The number and location of the tumor was comparable for the two groups. We observed a statically significant reduction in fibroid size from the treatment initiation until completion of three months, (41.06 ± 6.68 mm3 vs 35.16 ± 6.67 mm3) p = .0001. However, the decrease in fibroid size from 1st month to the 3rd month was not statistically significant, p = .189 (36.71 ± 5.54 mm3 vs 35.16 ± 6.67 mm3). CONCLUSION: This study shows that treatment with atorvastatin might positively reduce the size of fibroids. The decrease was only statistically significant during the first month. Further studies with a detailed analysis of the intervention's clinical impact are required to consider statins as a therapeutic tool.

Ghaffari, F. and A. Arabipoor (2020). "Role of surgery in treatment of infertile women with endometriosis: A review study." Iranian Journal of Obstetrics, Gynecology and Infertility 23(8): 75-86.
	Introduction: Endometriosis is a chronic inflammatory disease which affects fertility. This study was performed with aim to evaluate the clinical role of surgical intervention and assisted reproductive technology (ART) in infertile women with endometriosis on the basis of recent clinical guidelines. Method(s): In this review study, the published articles in the databases of PubMed, Science direct, Scopus, Google scholar were searched using the keywords of "endometriosis" and / or "endometrioma" and / or "assisted reproductive technology" and / or "infertility" and / or "laparoscopy" and / or "cystectomy" and / or "surgery" and/ or "guideline" from January of 2000 to November 2019. All guidelines published in English in the field of laparoscopy and surgery in endometriosis and infertility were reviewed. Result(s): Until now, 6 international guidelines have been published in this field and we reviewed these articles in the present study. According to the recent evidences, laparoscopy is not routinely performed prior to ART and its clinical application is to diagnose mild from moderate endometriosis; however surgical resection is considered if mild endometriosis is present, as it may improve the spontaneous pregnancy rate. In the case of more severe types of disease (endometrioma and deep penetrating endometriosis), the benefits of pre-ART surgery are still unclear and its risks and benefits should be assessed. Conclusion(s): Based on the available guidelines, it is suggested that decision for surgery in infertile women with endometriosis should be made individually and on the basis of the patient' selection, age and ovarian reserve, association with annoying symptoms, other causes of infertility, location of lesion and possible risk of repeated surgery.Copyright © 2020, Mashhad University of Medical Sciences. All rights reserved.

Ghahremani, T., et al. (2022). "Women's Mental Health Services and Pregnancy: A Review." Obstetrical and Gynecological Survey 77(2): 122-129.
	Importance The importance of women's mental health services is becoming more evident as we learn more about the impact of mental health on maternal and perinatal outcomes. Objective The purpose of this review is to identify the importance of mental health issues arising during pregnancy including prevention, timely diagnosis and treatment, and referral to specialized services. Evidence Acquisition A literature search was undertaken using the search engines PubMed, CINAHL, and PsycINFO. The search terms were as follows: "mental health services"or "behavioral health"or "mental health counseling"or "psychological"and "delivery of health care"and "pregnancy"or "pregnant."The years searched were January 2000 to November 2020. The search was limited to English language. Results Of the 255 abstracts identified and reviewed, 35 full-text articles were the basis of this review. Literature summarizing the availability and models of care for mental health services for pregnant women is limited. After reviewing the literature, the themes of depression and anxiety in the antepartum and postpartum periods that emerged as mental health issues, especially during adolescent pregnancies, the coronavirus pandemic, intimate partner violence, and pregnancy loss, are of primary importance to obstetrical providers. All of these issues can have a significant impact on maternal and neonatal outcomes and should be addressed during routine practice. Conclusions and Relevance Maternal mental health is garnering deserved attention and has enormous implications on maternal and infant outcomes. Obstetrical providers should be comfortable with screening, identification, and basic treatment algorithms including when to refer to specialized services. Relevance Statement Mental health issues during pregnancy and the postpartum period can be profound with severe maternal and perinatal consequences. Target Audience Obstetricians and gynecologists, family physicians, psychiatrists. Learning Objectives After completing this activity, the learner should be better able to identify the mental health services that are available for pregnant women; outline the common mental illnesses that are present during adolescent pregnancies; explain the risk factors that have been linked with perinatal depression; and describe the management and potential complications of pregnant patients presenting with mental illness.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Ghajari, G., et al. (2023). "Mesenchymal Stem Cell-based Therapy and Female Infertility: Limitations and Advances." Current Stem Cell Research and Therapy 18(3): 322-338.
	Infertility in women can be caused by various female reproductive diseases such as premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis and Asherman syndrome that affect couples' quality of life and lead to mental, emotional, and physical problems. In recent years, clinical researchers have sought infertility treatments using new methods that are more effective and noninvasive than the old methods. Today, stem cell-based therapy has been introduced as a promising method and an alternative to the old strategy of infertility treatment. Understanding the main features and functional perspective of mesenchymal stem cells (MSCs) in the future of infertility by physicians is crucial. Mesenchymal stem cells (MSCs) are multipotent stem cells with a high proliferation range, abundant source and multidirectional differentiation potential. They have a high potential for the treatment of injured tissues in regenerative medicine through cell homing, secretion of active factors, and participation in immune regulation. At present, due to fewer ethical restrictions on the use of mesenchymal stem cells compared to embryonic stem cells, more attention has been paid to these cells as a new treatment for gynecological disorders. In this paper, we first review the various type of female reproductive disorders along with their common treatment methods, then we evaluate the recent advances in the application of MSCs in the diseases related to infertility and improve the reproductive health of women worldwide.Copyright © 2023, Bentham Science Publishers. All rights reserved.

Ghanaatgar-Kasbi, S., et al. (2022). "Targeting the Transforming Growth Factor-beta Signaling Pathway in the Treatment of Gynecologic Cancer." Current cancer drug targets 23(1): 15-24.
	The transforming growth factor-beta (TGF-β) signaling pathway has been reported to be dysregulated in the pathogenesis of several malignancies, including gynecologic cancers. This provides proof of concept of its potential value as a therapeutic target and prognostic biomarker in cervical cancer. Here we provide an overview of the biological role and clinical impact of TGF-β inhibitors either as a single agent or as a combinatorial therapy in gynecological cancers, concentrating on phase I to phase II/III clinical trials. Aberrant TGF-β signaling may lead to carcinogenesis. Inhibition of TGF-β represents an interesting area of focus for the treatment of gynecological cancer. Several TGF-β inhibitors are potential anticancer agents and are undergoing clinical trials in cancer, including galunisertib, dalantercept, and vigil. There is a growing body of data showing the potential therapeutic impact of targeting the TGF-β pathway in different cancer types, although further studies are still warranted to explore the value of this strategy and finding the most appropriate patients who could most benefit from therapy. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ghanbari, A., et al. (2021). "Tribulus terrestris and female reproductive system health: A comprehensive review." Phytomedicine : international journal of phytotherapy and phytopharmacology 84: 153462.
	BACKGROUND: Tribulus terrestris L. (T. terrestris) positive performance on the male sexual system has been confirmed, but little is known about its effects on the female reproductive system. PURPOSE: This review discussed in detail the beneficial impact of T. terrestris and its secondary metabolites on the female reproductive system. STUDY DESIGN AND METHODS: In this review, the scientific Databases of Science direct, Pubmed, Web of Science, Google, Google Scholar, Researchgate, EMBASE, Scientific Information (SID), and Elsevier were searched profoundly. Studies about the pharmacological activities of T. terrestris on the female reproductive system in each aspect of investigations: human, in vivo, and in vitro studies, in the period from 1998 to 2020 were admitted. Our study was not limited by the language of publications. RESULTS: 23 articles about the effects of T. terrestris on the female reproductive system were found. These studies approved the T. terrestris efficacy on improvements in histological features of the ovary and uterus of polycystic ovary syndrome patients as well as the well-working of normal ovaries, enhancements in the sexual desire of postmenopausal syndrome, improve ovarian and breast cancers. CONCLUSION: These studies showed that the positive effect of T. terrestris on the female reproductive system was due to the presence of a secondary metabolite called protodioscin; a steroidal saponin compound, as the dominant active component of this plant.

Ghanbari-Movahed, M., et al. (2021). "A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies." Frontiers in Pharmacology 12: 639840.
	Background: Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor formation and cancer cell growth. Naringin, a natural flavanone glycoside present in various plant species, has been indicated to modulate different signaling pathways and interact with numerous cell signaling molecules, which allows for an extensive variety of pharmacological actions, such as amelioration of inflammation, oxidative stress, metabolic syndromes, bone disorders, and cancer. The purpose of this systematic review is to present a critical and comprehensive assessment of the antitumor ability of naringin and associated molecular targets in various cancers. Method(s): Studies were identified through systematic searches of Science Direct, PubMed, and Scopus as well as eligibility checks according to predefined selection criteria. Result(s): Eighty-seven studies were included in this systematic review. There was strong evidence for the association between treatment with naringin alone, or combined with other drugs and antitumor activity. Additionally, studies showed that naringin-metal complexes have greater anticancer effects compared to free naringin. It has been demonstrated that naringin employs multitargeted mechanisms to hamper cancer initiation, promotion, and progression through modulation of several dysregulated signaling cascades implicated in cell proliferation, autophagy, apoptosis, inflammation, angiogenesis, metastasis, and invasion. Conclusion(s): The results of our work show that naringin is a promising candidate for cancer prevention and treatment, and might offer substantial support for the clinical application of this phytocompound in the future. Nevertheless, further preclinical and clinical studies as well as drug delivery approaches are needed for designing novel formulations of naringin to realize the full potential of this flavonoid in cancer prevention and intervention.© Copyright © 2021 Ghanbari-Movahed, Jackson, Farzaei and Bishayee.

Gharaei, H. and N. Gholampoor (2023). "The Role of Interventional Pain Management Strategies for Neuropathic Pelvic Pain in Endometriosis." Pain Physician 26(5): E487-E495.
	Background: Endometriosis is a chronic common condition affecting 10% of reproductive-aged women globally. It is caused by the growth of endometrial-like tissue outside the uterine cavity and leads to chronic pelvic pain, affecting various aspects of a woman's physical, mental, emotional, and social well-being. This highlights the importance of an understanding of the potential involvement of the nervous system and involved nerves as well as an effective multidisciplinary pain management. Objective(s): Our aim was to assess the current understanding of pain mechanisms in endometriosis and the effectiveness of different interventional pain management strategies. Study Design: Literature review. Method(s): A search was conducted using multiple databases, including Google Scholar, MEDLINE (Ovid), PubMed, and Embase. We used keywords such as "endometriosis," "pain," pelvic pain, "management," and "anaesthesia" along with Boolean operators and MeSH terms. The search was limited to English language articles published in the last 15 years. Result(s): Nerve involvement is a well-established mechanism for pain generation in patients with endometriosis, through direct invasion, irritation, neuroangiogenesis, peripheral and central sensitization, and scar tissue formation. Endometriosis may also affect nerve fibers in the pelvic region, causing chronic pelvic pain, including sciatic neuropathy and compression of other pelvic nerves. Endometriosis can cause sciatica, often misdiagnosed due to atypical symptoms. Interventional pain management techniques such as superior hypogastric plexus block, impar ganglion block, S3 pulsed radiofrequency, myofascial pain trigger point release, peripheral nerve hydrodissection, and neuromodulation have been used to manage persistent and intractable pain with positive patient outcomes and improved quality of life. Limitation(s): The complex and diverse clinical presentations of endometriosis make it challenging to compare the effectiveness of different pain management techniques. Conclusion(s): Endometriosis is a complex condition causing various forms of pain including nerve involvement, scar tissue formation, and bowel/bladder symptoms. Interventional pain management techniques are effective for managing endometriosis-related pain.Copyright © 2023, American Society of Interventional Pain Physicians. All rights reserved.

Ghasemi, T., et al. (2022). "Ethanol Sclerotherapy versus Laparoscopic Surgery in Management of Ovarian Endometrioma; a Randomized Clinical Trial." Archives of academic emergency medicine 10(1): e55.
	Introduction: A variety of therapeutic modalities are available in management of ovarian endometrioma. This study aimed to compare the effects of ethanol sclerotherapy and laparoscopic surgery on disease recurrence and ovarian factors of these patients.; Methods: 70 women with ovarian endometrioma and chronic pelvic pain were randomly divided into two groups. The first group underwent sclerotherapy with a puncture needle (cook) and the second group underwent laparoscopic surgery. Both groups were followed up every three months to investigate the recurrence rate. In this regard, ultrasonography was performed 3 months and 12 months after treatment, and serum anti-Müllerian hormone (AMH) levels were also reassessed 12 weeks after the intervention.; Results: 70 women with the mean age of 31.46 ± 4.71 years, and the mean body mass index (BMI) of 23.12 ± 1.01 were studied. The two groups were similar regarding age (p = 0.770), BMI (p = 0.371), history of gastrointestinal signs (p = 0.794), history of urinary diseases (p = 0.324), dysmenorrhea (p = 0.403), pelvic pain (p = 0.454), dyspareunia (p = 0.448), location of cyst (p = 0.448), and diameter of cyst (p = 0.250). In the laparoscopic group, a significant decrease in anti-Müllerian hormone (AMH) levels was observed after 12 weeks (p < 0.0001), while in the sclerotherapy group, no significant changes were found between pre-and post-operative AMH levels (p = 0.120). Cyst size decreased significantly in both groups three months (p < 0.001) and twelve months (p < 0.0001) after treatment. In the third month, 8 patients in the sclerotherapy group and 13 patients in the laparoscopic group had recurrences, and in the twelfth month, 17 patients in the sclerotherapy group and 15 patients in the laparoscopic group had recurrence of symptoms (p > 0.05).; Conclusions: Although AMH level and mean cyst diameter were significantly lower one year after laparoscopy, recurrence rate of ovarian endometrioma was similar between ethanol sclerotherapy and laparoscopy methods.; Competing Interests: The authors declare that there is no conflict of interest.

Ghijselings, L., et al. (2021). "Clinical efficacy of transcutaneous tibial nerve stimulation (TTNS) versus sham therapy (part I) and TTNS versus percutaneous tibial nerve stimulation (PTNS) (part II) on the short term in children with the idiopathic overactive bladder syndrome: protocol for part I of the twofold double-blinded randomized controlled TaPaS trial." Trials 22(1): 247.
	Background: Transcutaneous tibial nerve stimulation (TTNS) and percutaneous tibial nerve stimulation (PTNS) are effective and safe therapies for overactive bladder (OAB) syndrome in adults. However, few randomized sham‐controlled trials have been conducted in a pediatric population. To our knowledge, both therapies never have been compared in children. Aim: The aim of the complete study is twofold: (1) to assess the efficacy of TTNS therapy on bladder symptoms after 12 weeks of treatment in a pediatric population with idiopathic overactive bladder syndrome (iOAB) and/or nocturnal enuresis (part I) and (2) to assess the effect of TTNS compared to PTNS (part II). In this article, we aim to present the protocol of the first part of the TaPaS trial (TTNS, PTNS, sham therapy). Methods: Part I of the TaPaS trial is set up as a single‐center randomized‐controlled trial. Children, aged from 5 to 12 years with iOAB and/or nocturnal enuresis, are assigned to two groups by computer‐generated randomization: TTNS therapy (intervention) and sham therapy (control). The primary outcome is the percentage difference in average voided volume (AVV) between baseline and after 12 weeks of treatment. Secondary endpoints are the percentage difference in supervoid volumes, number of urinary incontinence episodes/24 h and in voiding frequency, the difference in parent reported outcomes between baseline and after 12 weeks of treatment, and the duration of clinical response. Discussion: We hypothesize that TTNS is a non‐inferior treatment for iOAB in children compared to PTNS therapy. Since literature is inconclusive about the efficacy of TTNS in a pediatric population, a sham‐controlled RCT on TTNS will be conducted (part I). A protocol for a prospective randomized sham‐controlled trial has been developed. Enrolment has started in November 2018. Study completion of part I is expected by August 2021. Trial registration: ClinicalTrials.gov NCT 04256876. Retrospectively registered on February 5, 2020.

Ghirardi, V., et al. (2023). "Diagnostic and Therapeutic Pathway of Advanced Ovarian Cancer with Peritoneal Metastases." Cancers 15(2): 407.
	Over two thirds of ovarian cancer patients present with advanced stage disease at the time of diagnosis. In this scenario, standard treatment includes a combination of cytoreductive surgery and carboplatinum-paclitaxel-based chemotherapy. Despite the survival advantage of patients treated with upfront cytoreductive surgery compared to women undergoing neo-adjuvant chemotherapy (NACT) and interval debulking surgery (IDS) due to high tumor load or poor performance status has been demonstrated by multiple studies, this topic is still a matter of debate. As a consequence, selecting the adequate treatment through an appropriate diagnostic pathway represents a crucial step. Aiming to assess the likelihood of leaving no residual disease at the end of surgery, the role of the CT scan as a predictor of cytoreductive outcomes has shown controversial results. Similarly, CA 125 level as an expression of tumor load demonstrated limited applicability. On the contrary, laparoscopic assessment of disease distribution through a validated scoring system was able to identify, with the highest specificity, patients undergoing suboptimal cytoreduction and therefore best suitable for NACT-IDS. Against this background, with this article, we aim to provide a comprehensive review of available evidence on the diagnostic and treatment pathways of advanced ovarian cancer.Copyright © 2023 by the authors.

Ghirardi, V., et al. (2023). "Current and future trials about HIPEC in ovarian cancer." Bulletin du cancer.
	Due to the typical peritoneal spread of the disease, together with cytoreductive surgery and adjuvant platinum-based chemotherapy, the role of hyperthermic intraperitoneal chemotherapy (HIPEC) is gainig more interest in advanced ovarian cancer (AOC) treatment. Indeed, the addition of hyperthemia seems to enhance the cytotoxic effect of chemotherapy directly delivered on peritoneal surface. So far, data on HIPEC administration during the primary debulking surgery (PDS) have been controversial. Indeed, despite flaws and biases, a survival advantage in a subgroup analysis of a prospective randomized trial of PDS+HIPEC treated patients was not demonstrated, whilst positive results are coming from a large retrospective cohort of patients treated with HIPEC after upfront surgery. In this setting, larger prospective data from an ongoing trial are expected by 2026. Contrariously, the addition of HIPEC with cisplatin 100mg/m 2 at the time of interval debulking surgery (IDS) has shown to prolong both progression-free and overall survival by prospective randomized data, despite few controversies on the methodology and the results of this trial arose among the experts. So far, available high quality data on HIPEC treatment after surgery for disease recurrence failed to demonstrate a survival benefit in this group of patients, however few trials are ongoing and results are awaited. With this article, we aim to discuss the main findings of available evidence and the objectives of ongoing trials on the addition of HIPEC to various timing of cytoreductive surgery in AOC, also in view of the development of precision medicine and targeted therapies in AOC treatment. (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Ghogare, A. S., et al. (2023). "Beyond the Antidepressant Action, Paroxetine in Managing the Hot Flashes in Women with Menopause: A Systematic Review." Global Journal of Medical Pharmaceutical and Biomedical Update 18(31): 18.
	Background: Women in the menopausal phase of their lives often experience the vasomotor symptoms of menopause, namely, hot flushes or flashes and disturbances of sleep. About 75-85% of menopausal women tend to experience one or more vasomotor symptoms of menopause. Menopausal hormone therapy (MHT) is considered to be the mainstay treatment in treating vasomotor symptoms of menopause. However, MHT tends to be accompanied by adverse outcomes and there exist contraindications to it. Hence, an alternative treatment strategy is required in view of contraindications, intolerance, or side effects of MHT. Recently, paroxetine is the first and only selective serotonin reuptake inhibitor antidepressant which is United States Food and Drug Administration approved as a non-hormonal management method of vasomotor/climacteric symptoms in menopausal women. Objective(s): In the present study, we systematically reviewed paroxetine's role in the management of hot flashes in menopausal women. Material(s) and Method(s): For the review purpose, we included the previously published relevant original, review, meta-analysis, and randomized controlled trial articles that were published in the English language using a 4-phase process of the preferred reporting items for systematic reviews and meta-analyses statement. Result(s): The severity and frequency of hot flashes were significantly reduced among menopausal women who received paroxetine compared to placebo. Five studies also showed improvement in the night-time sleep duration among menopausal women who received paroxetine in low doses. Conclusion(s): Thus, this study shows that low-dose paroxetine can be a beneficial and effective non-hormonal management option in managing hot flashes among menopausal women.Copyright © The Author(s) 2023.

Gholamalizadeh, M., et al. (2023). "The effects of dietary supplements in patients with cervical cancer: a comprehensive systematic review." European Journal of Obstetrics & Gynecology and Reproductive Biology: X 19: 100217.
	Background: Recent studies reported that complementary therapy including dietary supplements may has a beneficial role in cervical cancer. However, the results are inconsistent. This study aimed to investigate the association between cervical cancer and dietary supplements.; Methods: A systematic literature review was conducted to summarize and quantify the most recent findings on dietary supplement and cervical cancer. Several databases were checked for relevant publications published in English up to March 2023. Of the 32 articles identified, only 20 met the inclusion criteria and were included.; Results: Women with cervical intraepithelial neoplasia may benefit from folate supplementation against oxidative stress and inflammation. Vitamin D may reduce oxidative stress and may have a therapeutic effect. Zinc promotes the clearance of the human papilloma virus and reduces the chance of viral infection. The use of probiotic supplements may improve the complications associated with chemotherapy in patients with cervical cancer, such as diarrhea and abdominal pain. Radiotherapy and chemotherapy complications may also be reduced by omega-3 fatty acids.; Conclusion: Some dietary supplements including folate, vitamin D, zinc, probiotics, and omega-3 fatty acids may have beneficial effects in patients with cervical cancer. Further studies are warranted to confirm these results.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. (© 2023 The Authors.)

Gholami, A., et al. (2022). "The efficacy of soy isoflavones combined with soy protein on serum concentration of interleukin-6 and tumour necrosis factor-α among post-menopausal women? A systematic review and meta-analysis of randomized controlled trials." Clinical and Experimental Pharmacology & Physiology 49(1): 10-24.
	The post-menopausal stage in women's life is associated with the enhancement of inflammation that may be reduced using soy isoflavones or soy protein. The present study aimed to summarize the effect of soy isoflavones plus soy protein on circulating interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in post-menopausal women. The English-language articles were identified from the databases such as Cochrane Library, clinicaltrials.gov, Web of Science, PubMed, and Scopus until December 2020. The mean change from baseline and its standard deviation (SD) for intervention and comparison groups were used to calculate the effect size. The statistical heterogeneity of the intervention effects was computing by Cochran's Q test and I 2 statistic. Nine and seven studies were selected for systematic review and meta-analysis, respectively. The results of our meta-analysis indicated a non-significant effect on the serum concentrations of IL-6 and TNF-α (weighted mean differences [WMD] = 0.07 pg/mL; 95% confidence interval [CI] = -0.03, 0.17 pg/mL; P = 0.190; WMD =0.05 pg/mL; 95% CI = -0.01, 0.12 pg/mL; P = 0.092; respectively). In subgroup analysis, soy isoflavones plus soy protein could increase the serum concentration of IL-6 in studies with soy isoflavones dose ≤87 mg/days, cross-over design, weak quality, and studies on participants who had health risk factors or diseases. The serum concentration of TNF-α increased in studies with cross-over design, intervention duration ≤56 days, and body mass index (BMI) >27, and in studies that were conducted on at-risk or sick participants. In conclusion, our meta-analysis did not confirm any significant effect on serum concentration of IL-6 and TNF-α among post-menopausal women. (© 2021 John Wiley & Sons Australia, Ltd.)

Ghorayeb Joe, H., et al. (2023). "Dorsal root ganglion stimulation for the treatment of chronic pelvic pain: A systematic review." Pain practice : the official journal of World Institute of Pain 23(7): 838-846.
	Background: Chronic pelvic pain (CPP) is a difficult condition to treat. Due to complex pelvic innervation, dorsal column spinal cord stimulation (SCS) has not been shown to produce the same effect as dorsal root ganglion stimulation (DRGS) given emerging evidence suggesting that applying DRGS may result in favorable outcomes for individuals with CPP. The aim of this systematic review is to investigate the clinical use and effectiveness of DRGS for patients with CPP.; Materials and Methods: A systematic review of clinical studies demonstrating the use of DRGS for CPP. Searches were conducted using four electronic databases (PubMed, EMBASE, CINAHL, and Web of Science) across August and September 2022.; Results: A total of nine studies comprising 65 total patients with variable pelvic pain etiologies met the inclusion criteria. The majority of subjects implanted with DRGS reported >50% mean pain reduction at variable times of follow-up. Secondary outcomes reported throughout studies including quality of life (QOL) and pain medication consumption were reported to be significantly improved.; Conclusions: Dorsal root ganglion stimulation for CPP continues to lack supportive evidence from well-designed, high-quality studies and recommendations from consensus committee experts. However, we present consistent evidence from level IV studies showing success with the use of DRGS for CPP in reducing pain symptoms along with reports of improved QOL through periods as short as 2 months to as long as 3 years. Because the available studies at this time are of low quality with a high risk of bias, we strongly recommend the facilitation of high-quality studies with larger sample sizes in order to better ascertain the utility of DRGS for this specific patient population. At the same time, from a clinical perspective, it may be reasonable and appropriate to evaluate patients for DRGS candidacy on a case-by-case basis, especially those patients who report CPP symptoms that are refractory to noninterventional measures and who may not be ideal candidates for other forms of neuromodulation. (© 2023 World Institute of Pain.)

Ghorbani, Z., et al. (2021). "The Effect of Panax ginseng on Genitourinary Syndrome in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial." Complementary Medicine Research 28(5): 419-426.
	BACKGROUND: Menopause and estrogen deprivation cause a rise in the number of urogenital tract complaints. OBJECTIVE: This study was conducted to assess the effectiveness of ginseng on genitourinary syndrome. METHODS: This randomized trial was conducted on 60 postmenopausal women with genitourinary syndrome. The participants were randomly allocated to ginseng and placebo groups twice daily for 4 weeks. Vaginal maturation index and vaginal pH were evaluated before and 4 weeks after intervention as the primary outcomes. Also, the atrophic vaginitis and incontinence questionnaires were completed before and after intervention as the secondary outcomes. The safety of intervention was assessed by the side effects checklist. RESULTS: No significant differences were observed between the 2 groups in objective symptoms after the intervention, but the difference was statistically significant (p < 0.001) in terms of subjective symptoms of atrophic vaginitis. One case of insomnia and palpitation and 2 cases of hot flashes were reported in the intervention group, and 1 case of gastric discomfort and change in urine appearance was reported in the placebo group. CONCLUSION: Ginseng only improved the patient-assessed symptoms and had no significant effect on the clinician-assessed outcomes. Further studies are required to determine the precise pharmacological mechanisms of ginseng on genitourinary syndrome.

Giampaolino, P., et al. (2019). "Role of Ovarian Suspension in Preventing Postsurgical Ovarian Adhesions in Patients with Stage III-IV Pelvic Endometriosis: A Systematic Review." Journal of Minimally Invasive Gynecology 26(1): 53-62.
	Endometriosis is a benign complex gynecologic condition with high morbidity that affects women of reproductive age. Pelvic adhesion formation represents a serious clinical challenge in the management of patients with endometriosis. Several interventions aimed at reducing postoperative ovarian adhesion formation have been proposed in recent years. Here we summarize the published evidence on the efficacy of ovarian suspension in preventing postoperative ovarian adhesion formation in women undergoing laparoscopic surgery for stage III-IV endometriosis. The research was conducted using electronic databases. A review of the abstracts of all references retrieved from the search was conducted. Selection criteria for the systematic review included all randomized controlled trials (RCTs) and nonrandomized studies (NRSs) of premenopausal women diagnosed with stage III-IV pelvic endometriosis who underwent ovarian suspension or no ovarian suspension (control group). The RCTs were eligible for meta-analysis. Eight studies, 2 RCTs and 6 NRSs, were included in the systematic review. In all 8 studies, ovarian suspension was performed during surgery for stage III-IV endometriosis. The site of the suspension was the anterior abdominal wall in 76.8% of the cases. Five studies reported the use of polypropylene as suture for the suspension. Removal of the suspension suture in the postoperative period was reported in 6 studies. Pooled data from a meta-analysis of the RCTs show that women who underwent ovarian suspension had a significantly lower incidence of postoperative adhesion formation, particularly of moderate to severe adhesions. Ovarian suspension may reduce the rate and severity of postoperative adhesions formation in women undergoing laparoscopy for the treatment of stage III-IV endometriosis; however, RCTs with larger sample sizes are needed. (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

Giannini, A., et al. (2022). "The giant steps in surgical downsizing toward a personalized treatment of vulvar cancer." The Journal of Obstetrics and Gynaecology Research 48(3): 533-540.
	The present article aims to highlight the importance of changes of personalized surgical treatment for vulvar cancer. Current international literature regarding surgical treatment of vulvar cancer was evaluated. This included several studies and systematic reviews. Radical surgery approach, such as en bloc resection, was the first therapeutic option and the standard care for many years, even if burdened with a high complication rate and frequently disfiguring. Taussing and Way introduced radical vulvectomy approach with en bloc bilateral inguinal-femoral lymphadenectomy; modified radical vulvectomy was developed, with a wide radical excision of the primary tumor. The role of inguinofemoral lymphadenectomy (mono or bilateral) changed in the years too, particularly with the advent of SLN biopsy as minimally invasive surgical approach for lymph node staging, in patients with unifocal cancer <4 cm, without suspicious groin nodes. More personalized and conservative surgical approach, consisting of wide local or wide radical excisions, is necessary to reduce complications as lymphedema or sexual disfunction. The optimal surgical management of vulvar cancer needs to consider dimensions, staging, depth of invasion, presence of carcinoma at the surgical margins of resection and grading, with the goal of making the treatment as individualized as possible. (© 2021 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Giannini, A., et al. (2022). "Impact on ovarian reserve and fertility using carbon dioxide laser for endometriosis treatment: a systematic review." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(8): 617-622.
	Background The application of carbon dioxide (CO 2 ) laser for laparoscopic gynecologic surgery was introduced in 1979 and spread after improving instrumentation, due to the versatility of the CO 2 laser technology and the parallel increase of laparoscopic use. In a gynecologic setting, laser laparoscopy has been demonstrated to be effective in treating infertility and pain associated with mild to severe endometriosis.Aim and methods: This document aims at conducting a systematic review to provide a comprehensive literature overview regarding the rationale, indications, safety, and efficacy of CO 2 laser treatment of endometriosis and related outcomes on ovarian reserve and fertility. Results CO 2 laser seems to lead to lower heat damage in the ovarian tissue than bipolar energy during endometriomas treatment. Moreover, several reports have pointed out that laser vaporization allows to selectively destroy the endometrioma wall's internal surface, preserving the pericystic fibrotic capsule or the adjacent healthy ovarian cortex. Despite this, robust data we have so far indicates that the most effective laparoscopic approach for managing endometriomas is the traditional excisional technique providing better postoperative outcomes than drainage and electrocoagulation, and laser treatment. Data about fertility after treatment of deep infiltrating endometriosis (DIE) using dioxide laser are emerging but very poor. Conclusions Current scientific evidence in this field is inconclusive, and the debate about the safety and efficacy of the CO 2 laser on fertility outcomes is still ongoing. Further randomized case-control studies are mandatory to attain more consistent evidence.

Gien Lilian, T., et al. (2023). "Phase II activity trial of high-dose radiation and chemosensitization in patients with macrometastatic lymph node spread after sentinel node biopsy in vulvar cancer: GROningen INternational Study on Sentinel nodes in Vulvar cancer III (GROINSS-V III/NRG-GY024)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(4): 619-622.
	Background: Standard treatment of early-stage vulvar cancer is a radical, wide, local excision of the primary tumor and a sentinel lymph node (SLN) procedure for the groins. An inguinofemoral lymphadenectomy is no longer necessary for patients who have a negative SLN or micrometastasis ( ≤ 2 mm). When there is macrometastasis (>2 mm) in the SLN, an inguinofemoral lymphadenectomy is indicated; however, this procedure is associated with major morbidity, such as wound healing, lymphoceles, and lymphedema.; Primary Objective: To investigate the safety of replacing inguinofemoral lymphadenectomy by chemoradiation in patients with early-stage vulvar cancer with a macrometastasis (>2 mm) and/or extracapsular extension in the sentinel node.; Study Hypothesis: Combination of 56 Gy of radiation to the inguinal site and concurrent cisplatin chemotherapy without completion inguinofemoral lymphadenectomy will be feasible and safe, with low groin recurrence rates.; Trial Design: This is a single-arm, prospective phase II treatment trial with stopping rules for unacceptable groin recurrences. Eligible patients will receive 56 Gy of radiation to the involved inguinal site and chemotherapy with concurrent cisplatin.; Major Inclusion/exclusion Criteria: Eligible patients undergoing sentinel node procedure will have stage I, unifocal, invasive (>1 mm depth of invasion) squamous cell carcinoma of the vulva with tumor size <4 cm, and no suspicious nodes on imaging. Those eligible for the trial are those with a metastasis >2 mm in the sentinel node and/or extracapsular extension, or more than one sentinel node with micrometastasis ≤2 mm.; Primary Endpoint: Groin recurrence rate in the first 2 years after primary treatment.; Sample Size: 157 patients with macrometastases in their SLN.; Estimated Dates for Completing Accrual and Presenting Results: January 1, 2029.; Trial Registration Number: NCT05076942.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Giese, N. and K. Heirs Morag (2023). "Development of Provisional Acupuncture Guidelines for Pelvic Pain in Endometriosis Using an e-Delphi Consensus Process." Journal of Integrative and Complementary Medicine 29(3): 169-180.
	Introduction: Growing evidence suggests that acupuncture can improve pelvic pain in women with endometriosis. The treatments used in research vary considerably. It remains unclear which treatment could be recommended for clinical practice. This research project aimed at clarifying how acupuncture could be used when treating this condition. Methods: This research comprised two phases: a systematized literature review to extract acupuncture treatment details from published research, and an e-Delphi study to gain knowledge about details as used by expert acupuncturists. Review: Four databases were searched using predefined eligibility criteria. Data were extracted based on the STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. e-Delphi: Purposeful sampling from colleagues and international experts. An open first round gathered qualitative data, analyzed with the Framework method. In rounds 2 and 3, experts rated statements to build group consensus, defined as a rating of ≥5 on a 7-point Likert scale by ≥70% of the experts. The strength of agreement was graded using the median score and interquartile range. Results from the literature review and the e-Delphi were compared using the STRICTA items. Results: The literature review ( n = 29 unique studies) found a wide range of treatment details with little agreement. The e-Delphi of international experts ( n = 20) resulted in agreement on 94 statements (such as key factors for effectiveness); disagreement on a further 29 (such as acupressure); and absence of consensus on 55 statements (such as the number of needle insertions). A comparison of the review and e-Delphi results found little agreement. Conclusions: Details of acupuncture treatment for endometriosis-related pelvic pain were presented. In the absence of acupuncture guidelines for this condition, the researchers of this e-Delphi recommend using the treatment details on which experts agreed as guidance for good practice. The effectiveness of these guidelines should be evaluated in future research. Study registration: Deutsches Register Klinischer Studien, DRKS00022215, June 30, 2020, retrospectively registered.

Gil, G., et al. (2022). "Role of hysteroscopy during conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer in patients who desire pregnancy." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(8): 3435-3440.
	Twenty-five percent of cases of endometrial cancer appear in women with unfulfilled reproductive desires . An adequate selection of patients and a close hysteroscopic follow-up to monitor the endometrial response to the levonorgestrel-releasing intrauterine system (LNG-IUS) may be a valid and safe option for these patients . This is a case series and review of the literature study. We included eight patients diagnosed of complex endometrial hyperplasia with atypia (CEHA) or stage 1AG1 well-differentiated endometrial cancer without myometrial invasion who desired to get pregnant and opted for a conservative treatment. Follow-up was performed with hysteroscopy and directed biopsy at 3, 6 and 12 months. Of the 854 cases of complex endometrial hyperplasia with atypia (CEHA)/endometrial cancer were diagnosed, 2.3% were candidates for conservative management. We obtained a favourable regression of 71.2% at 6 months and 57% at one year with hormonal treatment. Conservative treatment in complex endometrial hyperplasia with atypia (CEHA)/low-grade endometrial cancer in reproductive age patients with a strong desire for pregnancy is feasible.

Gilandoust, A., et al. (2023). "The effect of cognitive behavioral therapy on symptoms on premenstrual syndrome and premenstrual dysphoric disorder." Advances in Cognitive Science 25(3): 64-76.
	Introduction: Menstruation is an essential event and the beginning of reproduction in a woman's life. However, some women suffer from menstrual disorders. This study aimed to determine the effect of cognitive behavioral therapy on the symptoms of premenstrual syndrome and premenstrual dysphoric disorders. Methods: This quasi-experimental study with pre-test, post-test and follow-up phases was con- ducted with a control group. The statistical population was all women who were referred to the gynecological and maternity clinics of Hamedan, Iran, in 2022. Forty people were selected by purposeful sampling method and randomly divided into four groups of ten people (two experimen- tal and two control groups). The experimental groups participated in cognitive behavioral therapy during eight weekly sessions of 60 minutes, but the control groups did not receive any intervention. A month and a half later, the follow-up phase was done. Data analysis was done by using SPSS-24 statistical software using univariate covariance analysis. Results: The results showed that cognitive behavioral therapy was effective in reducing pre- menstrual syndrome symptoms in the post-test phase (F=8.33, P<0.01) and the follow-up phase (F=28.05, P<0.000). Furthermore, this treatment was effective in reducing the symptoms of premenstrual dysphoric disorder in the post-test phase (F=9.36, P<0.007) and follow-up phase (F=21.97, P<0.000). Conclusion: Cognitive behavioral therapy was effective in reducing the symptoms of menstrual disorders, and its effects lasted for one and a half months after the intervention. Therefore, cognitive behavioral therapy should be used as a tool to improve society's overall health. Recommendedly, treatment programs should be established, comprehensive women's health education should be offered, and initiatives to enhance the mental health of women experiencing menstrual disorders must be prioritized. (PsycInfo Database Record (c) 2024 APA, all rights reserved)

Gilchrist Robert, B., et al. (2024). "A fresh start for IVM: capacitating the oocyte for development using pre-IVM." Human Reproduction Update 30(1): 3-25.
	Background: While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices.; Objective and Rationale: The objectives of this review are to examine the major scientific advances in ovarian biology with a unique focus on the development of pre-IVM methodologies, to provide an insight into biphasic IVM procedures, and to report on outcomes from animal and clinical human data, including safety data. The potential future impact of biphasic IVM on ART practice is discussed.; Search Methods: Peer review original and review articles were selected from PubMed and Web of Science searches for this narrative review. Searches were performed using the following keywords: oocyte IVM, pre-IVM, biphasic IVM, CAPA-IVM, hCG-triggered/primed IVM, natural cycle IVF/M, ex-vivo IVM, OTO-IVM, oocyte maturation, meiotic competence, oocyte developmental competence, oocyte capacitation, follicle size, cumulus cell (CC), granulosa cell, COC, gap-junction communication, trans-zonal process, cAMP and IVM, cGMP and IVM, CNP and IVM, EGF-like peptide and IVM, minimal stimulation ART, PCOS.; Outcomes: Minimizing gonadotrophin use means IVM oocytes will be collected from small antral (pre-dominant) follicles containing oocytes that are still developing. Standard IVM yields suboptimal clinical outcomes using such oocytes, whereas pre-IVM aims to continue the oocyte's development ex vivo, prior to IVM. Pre-IVM achieves this by eliciting profound cellular changes in the oocyte's CCs, which continue to meet the oocyte's developmental needs during the pre-IVM phase. The literature contains 25 years of animal research on various pre-IVM and biphasic IVM procedures, which serves as a large knowledge base for new approaches to human IVM. A pre-IVM procedure based on c-type natriuretic peptide (named 'capacitation-IVM' (CAPA-IVM)) has undergone pre-clinical human safety and efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF.; Wider Implications: Over many decades, improvements in clinical IVM have been gradual and incremental but there has likely been a turning of the tide in the past few years, with landmark discoveries in animal oocyte biology finally making their way into clinical practice leading to improved outcomes for patients. Demonstration of favorable clinical results with CAPA-IVM, as the first clinically tested biphasic IVM system, has led to renewed interest in IVM as an alternative, low-intervention, low-cost, safe, patient-friendly ART approach, and especially for patients with PCOS. The same new approach is being used as part of fertility preservation in patients with cancer and holds promise for social oocyte freezing. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Gil-Ibanez, B., et al. (2023). "Side effects screening and early intervention to impact in quality of life of patients with gynecological cancers (HALIS study)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(10): 1645-1648.
	Background: Advances in the treatment of gynecological cancers have led to increased survival in patients with gynecological cancers. Nevertheless, patients may still experience prevalent long term consequences, including lower limb lymphedema, depression, anxiety, sexual dysfunction, malnutrition, and sarcopenia, that negatively impact their quality of life.; Primary Objective: To assess the impact on self-perceived quality of life of systematic screening and early treatment of lower limb lymphedema, anxiety and depression, sexual dysfunction, and sarcopenia and malnutrition compared with standard practice.; Study Hypothesis: Systematic screening with validated questionnaires leading to early diagnosis and treatment of side effects will have a positive impact on quality of life.; Trial Design: This prospective clinical trial will randomize candidates for surgery to either standard of care or systematic screening every 2 months for 2 years. Quality of life data will be collected every 4 months. After randomization, patients in the control group will follow standard usual care. Their screening scales will not be considered. In the experimental group, positive screenings will generate an alert to the physician, and patients will be referred to the corresponding specific area (rehabilitation unit, psycho-oncology unit, sexual health unit, or nutrition unit).; Major Inclusion and Xclusion Criteria: Patients aged ≥18 years with ovarian, cervical, or endometrial cancer who are candidates for surgery will be included.; Primary Endpoint: Self-reported quality of life questionnaire score.; Sample Size: 168 patients will be randomized to detect a difference of 6 points in the questionnaires.; Estimated Dates for Completing Accrual and Presenting Results: Study completion is estimated for January 2026 and the results will be presented in May 2026.; Trial Registration Number: NCT05918770.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Gill, B., et al. (2023). "Safety, feasibility, and tolerability of estrogen and/or probiotics for improving vaginal health: A phase 1 clinical trial." American Journal of Reproductive Immunology 89(Supplement 1): 78.
	Problem: The vaginal microenvironment is central in mediating susceptibility to infection within the female genital tract (FGT). Studies suggest a polymicrobial environment coupled with reduced Lactobacillus colonization is associated with bacterial vaginosis (BV), vaginal inflammation, and an increased risk of HIV infection. Given the prevalence of BV among African/Caribbean/Black (ACB) women a prospective, randomized, open-label phase 1 clinical trial was conducted to determine the safety, tolerability, and feasibility of intravaginal estrogen and/or probiotic interventions for improving vaginal health in high-risk populations. Method of Study: Pre-menopausal ACB women aged 18-49 from the Toronto area were enrolled in a 30-day intervention with samples collected at baseline, with subsequent randomization to four treatment groups including: low dose intravaginal estradiol (Estring; 7.5 mg/day), a twice daily vaginal probiotic (RepHresh Pro-B; 1 x 107 cfu total of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 per capsule), and a combination of both an oral or vaginal probiotic with the Estring. A 1-week follow-up was conducted after 30 days, for a final assessment among participants who completed the study. Feasibility was evaluated through enrolment, retention, and intervention protocol (IP) adherence rates. In addition, safety and tolerability were assessed according to adverse events (AEs) recorded during the intervention, in addition to comprehensive blood panels comprised of blood glucose, complete blood count, as well as metabolic and lipid profiles. Result(s): Over the duration of 2 years (November 2019-December 2021), 63 ACB women were screened, with 51 participants enrolled, and 41 completing the intervention. Accordingly, enrollment and retention rates were 81% and 83%, exceeding the set targets of 70% and 80%, respectively. Overall, a total of six (12%) participants withdrew consent, four (8%) withdrew due to IP non-compliance, and one (2%) was lost to follow up. Of those that completed the study, an acceptable IP adherence of 94% (IQR 93%-100%) and 91% (IQR 87%-100%) was established for both overall Estring and probiotic groups, respectively. In addition, no significant difference in IP adherence was observed between the four treatment arms (p > .05). Safety and tolerability results indicated a total of 92 AEs reported by 29 (57%) participants, of which 66 (72%) were mild in intensity and 86 (93%) resolved by the end of the study. Specifically, vaginal irritation/burning/itching, cramps/abdominal pain, and headache were among the most frequently reported AEs, with vaginal irritation/ burning/itching being the only AE reported more than once by multiple participants (5, 11%). Three (7%) participants reported cramps/abdominal pain, headache, light headedness, and/or nausea of severe intensity 1-2 times over the course of the 30 days, all of which resolved by study completion. Moreover, comprehensive blood panels exhibited no significant change (p > .05) between baseline and study completion, with concentrations and counts found within a healthy clinical range for all participants. Conclusion(s): Our results demonstrate acceptable enrollment, retention, and adherence, with no severe AEs reported. Overall, this study indicates that the administration of intravaginal estrogen and probiotics, either in combination or alone are safe, tolerable as well as feasible interventions for pre-menopausal ACB women.

Gillis Brenna, D. and L. Parish Abby (2019). "Group-based interventions for postpartum depression: An integrative review and conceptual model." Archives of Psychiatric Nursing 33(3): 290-298.
	This integrative review explores how and to what extent group-based therapy and social support interventions affect women's recovery from postpartum depression (PPD). Thirteen articles from three databases met inclusion criteria. The studies revealed that a group environment of acceptance and understanding set a foundation for women to share their experiences with PPD. As women shared challenges, wisdom, and guidance within the group, they attained positive outcomes: validation, empowerment, and improvements in depressive symptoms. An integrated conceptual model was created to depict the identified characteristics and outcomes of PPD groups; clinicians can use the model to optimize group-based PPD interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Gimovsky Alexis, C., et al. (2022). "Prolonged second stage effect on pelvic floor dysfunction: a follow up survey to a randomized controlled trial." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(25): 5520-5525.
	Background: Pelvic floor dysfunction is a group of disorders that can significantly impact quality of life due to persistent urinary and anal incontinence. Data evaluating the effect of prolonged second stage of labor and postpartum pelvic floor dysfunction is heterogenous and limited.; Objective: To evaluate whether extending the length of labor in nulliparous women with prolonged second stage affects the presence of self-reported pelvic floor dysfunction after a randomized controlled trial of prolonged second stage.; Study Design: We conducted a planned follow up survey to our randomized controlled trial of prolonged second stage of labor using the Pelvic Floor Distress Inventory-20 (PFDI-20). The primary outcome was the PFDI-20 summary score. Secondary outcomes included urinary and fecal incontinence, prolapse, and patient satisfaction. Women surveyed were nulliparous patients with epidural anesthesia, previously enrolled in a randomized controlled trial that assigned them to extended labor , at least 1 additional hour in the second stage if they were undelivered after three hours, or to usual labor , defined as expedited delivery after three hours in the second stage. Women were surveyed at 12 - 36 months postpartum.; Results: Thirty-four of the seventy-eight women responded to the survey (43.6%). 17 women (50.0%) were from the extended labor group and 17 from the usual labor group (50.0%). Maternal demographic data were not significantly different between groups. The PFDI-20 summary score was 13.8 ± 23.3 in the extended labor group and 13.1 ± 20.9 in the usual labor group ( p = 0.9). The Pelvic Organ Prolapse Distress Inventory-6 was 1.2 ± 2.9 in the extended labor group and 2.7 ± 6.4 in the usual labor group ( p = 0.4). The Colorectal-Anal Distress Inventory-8 was 0.8 ± 2.8 in the extended labor group and 2.1 ± 4.0 in the usual labor group ( p = 0.6). The Urinary Distress Inventory-6 was 11.8 ± 21.1 in the extended labor group and 8.3 ± 14.5 in the usual labor group ( p = 0.6). Maternal and neonatal outcomes, as well as patient satisfaction, were not statistically significantly different between groups.; Conclusion: Extending the length of labor in nulliparas with singleton gestations, epidural anesthesia, and prolonged second stage did not have an impact on PFDI-20 scores at 12-36 months postpartum. However, our study was underpowered to detect small, but potentially clinically important, differences.; Clinical Trial Number: NCT02101515 (Study Registration Date March 28, 2014) https://clinicaltrials.gov/ct2/show/NCT02101515.

Gingold Julian, A., et al. (2019). "Perioperative Interventions to Minimize Blood Loss at the Time of Hysterectomy for Uterine Leiomyomas: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 26(7): 1234.
	Study Objective: Hysterectomy for uterine leiomyoma(s) is associated with significant morbidity including blood loss. A systematic review and meta-analysis was conducted to identify nonhormonal interventions, perioperative surgical interventions, and devices to minimize blood loss at the time of hysterectomy for leiomyoma.; Data Sources: Librarian-led search of Embase, MEDLINE, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases from 1946 to 2018 with hand-guided updates.; Methods of Study Selection: Included studies reported on keywords of hysterectomy, leiomyoma, and operative blood loss/postoperative hemorrhage/uterine bleeding/metrorrhagia/hematoma. The review excluded a comparison of route of hysterectomy, morcellation, vaginal cuff closure, hormonal medications, vessel sealing devices for vaginal hysterectomy, and case series with <10 patients.; Tabulation, Integration, and Results: Surgical blood loss, postoperative hemoglobin (Hb) drop, hemorrhage, transfusion, and major and minor complications were analyzed and aggregated in meta-analyses for comparable studies in each category. A total of 2016 unique studies were identified, 33 of which met the inclusion criteria, and 22 were used for quantitative synthesis. The perioperative use of misoprostol in abdominal hysterectomy (AH) was associated with a lower postoperative Hb drop (0.59 g/dL; 95% confidence interval [CI], 0.39-0.79; p < .01) and blood loss (-96.43 mL; 95% CI, -153.52 to -39.34; p < .01) compared with placebo. Securing the uterine vessels at their origin in laparoscopic hysterectomy (LH) was associated with decreased intraoperative blood loss (-69.07 mL; 95% CI, -135.20 to -2.95; p = .04) but no significant change in postoperative Hb (0.24 g/dL; 95% CI, -0.31 to 0.78; p = .39) compared with securing them by the uterine isthmus. Uterine artery ligation in LH before dissecting the ovarian/utero-ovarian vessels was associated with lower surgical blood loss compared with standard ligation (-27.72 mL; 95% CI, -35.07 to -20.38; p < .01). The postoperative Hb drop was not significantly different with a bipolar electrosurgical device versus suturing in AH (0.26 g/dL; 95% CI, -0.19 to 0.71; p = .26). There was no significant difference between an electrosurgical bipolar vessel sealer (EBVS) and conventional bipolar electrosurgical devices in the Hb drop (0.02 g/dL; 95% CI, -0.15 to 0.20; p = .79) or blood loss (-50.88 mL; 95% CI, -106.44 to 4.68; p = .07) in LH. Blood loss in LH was not decreased with the LigaSure (Medtronic, Minneapolis, MN) impedance monitoring EBVS compared with competing EBVS systems monitoring impedance or temperature (2.00 mL; 95% CI, -8.09 to 12.09; p = .70). No significant differences in hemorrhage, transfusion, or major complications were noted for all interventions.; Conclusion: Perioperative misoprostol in AH led to a reduction in surgical blood loss and postoperative Hb drop (moderate level of evidence by Grading of Recommendations, Assessment, Development and Evaluation guidelines) although the clinical benefit is likely limited. Remaining interventions, although promising, had at best low-quality evidence to support their use at this time. Larger and rigorously designed randomized trials are needed to establish the optimal set of perioperative interventions for use in hysterectomy for leiomyomas. (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

giorgia, D. and M. Andrea (2021). "Minimally invasive versus open surgery in women with high-risk endometrial cancer: a systematic review and meta-analysis, and a cohort study."
	
Giovannopoulou, E., et al. (2021). "The Emerging Role of Robotic Single-site Approach for Myomectomy: A Systematic Review of the Literature." Surgical innovation 28(3): 352-359.
	Objective. To review the existing studies on single-site robotic myomectomy and test the safety and feasibility of this innovative minimally invasive technique. Data Sources. PubMed, Scopus, Google Scholar (from their inception to October 2019), as well as Clinicaltrials.gov databases up to April 2020. Methods of Study Selection. Clinical trials (prospective or retrospective) that reported the outcomes of single-site robotic myomectomy, with a sample of at least 20 patients were considered eligible for the review. Results. The present review was performed in accordance with the guidelines for Systematic Reviews and Meta-Analyses (PRISMA). Four (4) studies met the inclusion criteria, and a total of 267 patients were included with a mean age from 37.1 to 39.1 years and BMI from 21.6 to 29.4 kg/m2. The mean operative time ranged from 131.4 to 154.2 min, the mean docking time from 5.1 to 5.45 min, and the mean blood loss from 57.9 to 182.62 ml. No intraoperative complications were observed, and a conversion rate of 3.8% was reported by a sole study. The overall postoperative complication rate was estimated at 2.2%, and the mean hospital stay ranged from 0.57 to 4.7 days. No significant differences were detected when single-site robotic myomectomy was compared to the multiport technique concerning operative time, blood loss, and total complication rate. Conclusion. Our findings support the safety of single-site robotic myomectomy and its equivalency with the multiport technique on the most studied outcomes. Further studies are needed to conclude on the optimal minimally invasive technique for myomectomy.

Girda, E., et al. (2022). "Phase I trial of daily subcutaneous SPL-108 injections in combination with paclitaxel in patients with platinum resistant CD44+ advanced ovarian epithelial cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Objective: Preclinical evidence and early clinical trials have demonstrated the activity of SPL-108, a targeted agent that inhibits CD44 mediated induction of multidrug resistance specifically to paclitaxel and platinum agents. We conducted a phase I, open label, dose escalation study of the safety and tolerability of the combination of SPL-108 with weekly paclitaxel in patients with platinum resistant CD44+ ovarian, primary peritoneal, or fallopian tube cancer.; Methods: Patients with platinum resistant histologically proven epithelial ovarian, primary peritoneal, or fallopian tube cancers and measurable disease according to RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 were selected. Tumors were tested for CD44 expression for eligibility, defined as strong (+++) or moderate (++) staining in ≥20% of the tumor tissue or diffuse + staining. Patients were treated with daily and then twice daily SPL-108 subcutaneous injections and weekly intravenous paclitaxel on days 1, 8, and 15 of a 28 day cycle. Endpoints included safety, determination of maximum tolerated dose, and efficacy. Tumors underwent comprehensive genomic profiling, and cell lines and western blotting were used to study markers of response.; Results: We screened 16 patients, and 14 were enrolled based on CD44+ expression. A total of 86% of patients had high grade serous tumors and all had received multiple prior therapies. There were no grade 4-5 toxicities. One patient had grade 3 peripheral sensory neuropathy attributed to paclitaxel and one patient developed presumed colonic perforation attributed to the study drug. No dose reductions or treatment discontinuations were required. All patients tolerated the maximum planned dose; no maximum tolerated dose was reached. Overall response rate was 36%; 5 (36%) patients had partial response and 5 (36%) patients had stable disease.; Conclusions: The combination of SPL-108 with weekly paclitaxel was safe and well tolerated. Encouraging antitumor activity was observed, with 72% of patients deriving a clinical benefit.; Trial Registration: NCT03078400.; Competing Interests: Competing interests: DN and MF have ownership options in Splash Pharmaceuticals. (© IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Giroux, M., et al. (2021). "A randomized comparison of training programs using a pelvic model designed to enhance pelvic floor examination in patients presenting with chronic pelvic pain." International Urogynecology Journal 32(2): 423-431.
	INTRODUCTION: Pelvic floor myalgia is a common cause and contributor to chronic pelvic pain [Neurourol Urodyn 4:984-1008 (2017)]. The purpose of this study was to compare in-person versus video-based teaching methods of a comprehensive assessment of the pelvic floor musculature on a pelvic model. METHODS: A randomized controlled trial of 46 participants was conducted. The participants were randomized into two groups. Both groups were taught by the same pelvic floor physiotherapist using two different teaching methods on a pelvic model. Group 1 watched an instructional video, whereas group 2 had in-person training. Both groups underwent pre- and post-training assessments consisting of a written examination and an Objective Structured Clinical Examination (OSCE). Primary outcome measure was the change in participants' pre- and post-training assessment scores. Secondary outcome measures were perceived changes in both participants' comfort level in performing pelvic floor examination and applicability of the training program to clinical practice. RESULTS: There was no statistically significant difference between the teaching methods in the degree of improvement of the participants' mean written assessment scores (p = 0.58), OSCE scores (p = 0.15), and perceived comfort level (p = 0.19). Participants' mean pre- and post-assessment scores improved significantly (p < 0.001). Participants reported the training program to be applicable towards their clinical practice. CONCLUSIONS: This study demonstrates that learners' assessment of pelvic floor musculature can be enhanced using varied teaching methods on a pelvic model.

Girtner, F., et al. (2021). "Randomized Crossover-Controlled Evaluation of Simultaneous Bilateral Transcutaneous Electrostimulation of the Posterior Tibial Nerve During Urodynamic Studies in Patients With Lower Urinary Tract Symptoms." International neurourology journal 25(4): 337‐346.
	Purpose: Transcutaneous tibial nerve stimulation (TTNS) has proven to be a valuable treatment option for various lower urinary tract conditions, such as overactive bladder syndrome and neurogenic detrusor overactivity. The aim of this study was to investigate acute changes in urodynamic parameters due to bilateral TTNS. Methods: Fifty‐one patients (18–87 years; 61% female) with various lower urinary tract symptoms were enrolled in this study. They were single‐blinded and randomly assigned to receive simultaneous bilateral TTNS either during their first urodynamic examination, followed by a second round using a placebo stimulation technique, or vice versa. Results: For subjects without signs of anatomical pathologies, the filling volume at the first desire to void (FDV) increased significantly by 54 mL (interquartile range [IQR], 26–81 mL; P < 0.01) under the influence of TTNS compared to placebo. The maximum cystometric capacity increased by 41 mL (IQR, 10–65 mL; P = 0.02). The median micturition volume of patients with pathological postvoid residual volumes (> 100 mL) increased by 76 mL compared to patients without urinary retention (IQR, 6–166 mL; P = 0.03). Conclusions: Compared to placebo, simultaneous bilateral TTNS showed significant improvements in bladder functioning, such as delayed FDV, increased maximum cystometric capacity, and reduced urinary retention. Patients with signs of anatomical pathologies did not seem to benefit from TTNS. Further studies need to be conducted to compare the effectiveness of bilateral versus unilateral TTNS.

Gish, B., et al. (2023). "Neuromodulation for the management of chronic pelvic pain syndromes: A systematic review." Pain practice : the official journal of World Institute of Pain.
	BACKGROUND: Chronic pelvic pain is a burdensome condition that involves multiple medical sub-specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large-scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes. MATERIALS AND METHODS: A systematic review of the literature demonstrating the treatment of chronic pelvic pain syndromes with neuromodulation. Abstracts were reviewed and selected for inclusion, including case series, prospective studies, and randomized controlled trials (RCTs). Case studies and publications in abstract only were not included. The reporting for this systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed using MEDLINE, Embase, Cochrane Library, PubMed, CINAHL, and Scopus. RESULTS: A total of 50 studies were included in this review, three of which were randomized controlled trials, and the remaining were prospective and retrospective case series. The range of pelvic pain conditions treated included interstitial cystitis, peripheral neuralgia, pudendal neuralgia, gastrointestinal pain, urogenital pain, sacroiliac joint pain, and visceral chronic pelvic pain. We reported on outcomes involving pain, functionality, psychosocial improvement, and medication reduction. CONCLUSIONS: Neuromodulation is a growing treatment for various chronic pain syndromes. Peripheral nerve stimulation was the least studied form of stimulation. Posterior tibial nerve stimulation appears to offer short-term benefit, but long-term results are challenging. Sacral nerve stimulation is established for use in functional bladder syndromes and appears to offer pain improvement in these patients as well. Dorsal root ganglion stimulation and spinal cord stimulation have been used for a variety of conditions with promising results. Further studies of homogeneous patient populations are necessary before strong recommendations can be made at this time, although pooled analysis may also be impactful.

Gislinge Julie Isabelle, P., et al. (2023). "Hormone replacement in premature ovarian insufficiency [Danish]." Ugeskrift for laeger 185(28).
	Premature ovarian insufficiency (POI) is defined as loss of ovarian function in women less-than 40 years. This review summarises the causes and the possible treatment options. POI can be idiopathic, caused by genetic, autoimmune, or metabolic disease, or be induced by cancer therapy or surgery. POI causes infertility, increased morbidity and mortality, and decreased quality of life. Hormonal replacement therapy (HRT) can alleviate symptoms of POI and should be initiated at diagnosis. The benefit of HRT outweighs the minor side effects in most cases and should be continued until age of natural menopause.

Gitas, G., et al. (2021). "Surgical outcomes of conventional laparoscopic and robotic-assisted hysterectomy." The international journal of medical robotics + computer assisted surgery : MRCAS 17(3): e2225.
	INTRODUCTION: The aim of the present study was to compare surgical outcomes of total laparoscopic hysterectomy with those of the robotic approach using the da Vinci Xi system. METHODS: Patients who underwent hysterectomy with da Vinci Xi for early endometrial cancer or benign indications from 2018 to 2019 were selected. The control group consisted of patients who underwent conventional laparoscopy. RESULTS: A total of 300 patients were included in the study. The mean duration of surgery differed significantly (p = 0.025) between those who underwent laparoscopy (125.01 ± 76.168) and robotic-assisted surgery (142.96 ± 82.657 min). Blood loss, median hospital stay, intraoperative and postoperative complications were similar in both groups. No statistical difference was observed in the subgroups with a body mass index of more than 30 kg/m2 or more than 40 kg/m2 concerning the duration of surgery or the surgical outcome. CONCLUSION: The da Vinci Xi did not improve surgical outcomes in patients who underwent hysterectomy by trained laparoscopists and takes more time than conventional laparoscopy when performed in patients of normal weight.

Gitas, G., et al. (2022). "Robotic surgery in gynecology: is the future already here?" Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 31(6): 815-824.
	Robotic-assisted surgery has gained widespread acceptance in the surgical community and appears to be the most rapidly developing sector of minimally invasive surgery. However, robotic surgery has been viewed as a development of, or alternative to, laparoscopic surgery and not necessarily as a superior technology. The advantages of MIS over open surgery apply to robotic-assisted surgery as well. Nevertheless, conflicting data have been published about the advantages and disadvantages of robotic-assisted and laparoscopic surgery. In the last few years, robotic-assisted surgery has been used for various gynecological procedures such as hysterectomy, lymphadenectomy, myomectomy, sacrocolpopexy or endometriosis operations. In the present review, we analyze the current use of robotic-assisted surgery and its efficiency in gynecology. Patient-based outcomes, such as quality of life and outcomes in morbidly obese patients are also addressed. The potential benefits of single-port robotic-assisted surgery are discussed. Most of the studies published so far state that robotic-assisted surgery does not essentially improve the surgical outcome compared to conventional laparoscopic surgery. However, randomized studies are scarce. Ongoing technological progress over the next few years may improve robotic-assisted techniques and thus optimize the patient's treatment.

Gitas, G., et al. (2023). "Role of laparoscopic hysterectomy in cervical and endometrial cancer: a narrative review." Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 32(1): 1-11.
	Endometrial cancer is the most common carcinoma of the female genital organs and cervical cancer is the leading cause of cancer death in women worldwide. The aim of this review is to evaluate the role of laparoscopic hysterectomy in patients with endometrial and cervical cancer in this period, and analyze the outcome of hysterectomy in terms of survival. Moreover, we present the historical background, new techniques, the anatomical features, and surgical steps of radical hysterectomy. According to new evidence, minimally invasive surgery in patients with cervical cancer is associated with higher rates of recurrence and mortality compared to the open approach. Despite the numerous explanations offered for this phenomenon, the reasons for these results are unclear. Additional large trials have been launched to reevaluate the above-mentioned data. On contrary, the laparoscopic approach provides surgical outcomes and similar survival rates as open surgery in patients with early endometrial carcinoma. Furthermore, the radicality of hysterectomy does not influence local recurrence rates or overall survival in cases with complete surgical removal of the tumor. A laparoscopic radical hysterectomy is no longer an option in patients with cervical cancer. When minimally invasive surgery is offered, the patients must be counseled in detail about the current debate.

Giudice, E., et al. (2021). "Tisotumab vedotin in cervical cancer: Current status and future perspectives." US Oncology and Hematology Review 17(2): 1-5.
	Despite the introduction of screening programmes and vaccination campaigns, cervical cancer (CC) still represents one of the leading causes of cancer-related mortality in women worldwide and the fourth most common female malignancy. The prognosis of CC remains poor, especially for late-stage and relapsed disease. While platinum-based chemotherapy with or without bevacizumab has been the established standard of care in the first-line setting, no standard second-line treatments have been identified, and new active agents are needed. Antibody-drug conjugates (ADCs) represent a novel class of agents approved by the US Food and Drug Administration to treat haematological malignancies and metastatic breast cancer. According to available data, ADCs could also represent a valid option for metastatic and recurrent CC. This review describes the role of tisotumab vedotin, an ADC targeting tissue factor, in the metastatic and recurrent CC setting. An overview of published data and ongoing clinical trials is also provided.Copyright © Touch Medical Media 2021.

Giudice, E., et al. (2023). "Recent progress in the use of pharmacotherapy for endometrial cancer." Expert Opinion on Pharmacotherapy 24(1): 83-94.
	Introduction: Endometrial cancer (EC) is the most common gynecological cancer in developed countries. The ESGO/ESTRO/ESP updated evidence-based guidelines in 2020, introducing molecular classification to guide EC treatment. The genomic-based approach has identified four prognostic subgroups of EC. Each of these may benefit from a tailored treatment depending on the molecular profile, the histotype, and stage of disease for the adjuvant and the metastatic/recurrent setting. Several clinical trials are now ongoing to identify the best treatment according to the molecular profile of EC.; Areas Covered: This review analyzes tailored treatment for EC according to the molecular profile, both in the adjuvant and in the metastatic/recurrent setting. The authors review the results of clinical studies and highlight ongoing trials.; Expert Opinion: Several new agents are under evaluation in order to personalize EC treatment according to specific molecular profiles in the adjuvant, advanced, and recurrent settings. Clinical trials investigating the impact of molecular classification have yielded encouraging results. EC can no longer be considered a single tumor entity susceptible to a single treatment modality but rather be split into four distinct types, requiring tailored treatments.

Giugale, L., et al. (2022). "Long-term Urinary Outcomes After Transvaginal Uterovaginal Prolapse Repair With and Without Concomitant Midurethral Slings." Female Pelvic Medicine & Reconstructive Surgery 28(3): 142-148.
	Importance: Many health care providers place concomitant midurethral slings during pelvic organ prolapse repair, yet growing evidence supports staged midurethral sling placement.; Objectives: The aim of this study was to compare urinary function after transvaginal uterovaginal prolapse repair with and without midurethral sling.; Study Design: Secondary analysis of the Study of Uterine Prolapse Procedures Randomized Trial (hysterectomy with uterosacral ligament suspension vs mesh hysteropexy). Our primary outcome was Urinary Distress Inventory score (UDI-6) through 5 years compared between women with and without a concomitant sling within prolapse repair arms. Sling effect was adjusted for select clinical variables and interaction terms (α = .05).; Results: The sling group included 90 women (43 hysteropexy, 47 hysterectomy), and the no-sling group included 93 women (48 hysteropexy, 45 hysterectomy). At baseline, the sling group reported more bothersome stress (66% vs 36%, P < 0.001) and urgency incontinence (69% vs 48%, P = 0.007). For hysteropexy, there were no significant long-term differences in UDI-6 scores or bothersome urine leakage between sling groups. For hysterectomy, women with sling had better UDI-6 scores across time points (adjusted mean difference, -5.1; 95% confidence interval [CI], -9.9 to -0.2); bothersome stress and urgency leakage were less common in the sling group (stress adjusted odds ratio, 0.1 [95% CI, 0.0-0.4]; urge adjusted odds ratio, 0.5 [95% CI, 0.2-1.0]). Treatment for stress incontinence over 5 years was similar in the sling (7.9%) versus no-sling (7.6%) groups.; Conclusions: Five-year urinary outcomes of concomitant midurethral sling may vary by type of transvaginal prolapse surgery, with possible benefit of midurethral sling at the time of vaginal hysterectomy with apical suspension but not after mesh hysteropexy. (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Giugale, L. E., et al. (2021). "Preoperative Pelvic Floor Injections With Bupivacaine and Dexamethasone for Pain Control After Vaginal Prolapse Repair: A Randomized Controlled Trial." Obstetrics and Gynecology 137(1): 21-31.
	OBJECTIVE: To test the hypothesis that preoperative pelvic floor muscle injections and pudendal nerve blocks with bupivacaine and dexamethasone would decrease postoperative pain after vaginal native tissue prolapse repairs, compared with saline and bupivacaine. METHODS: We conducted a three-arm, double-blind, randomized trial of bilateral transobturator levator ani muscle injections and transvaginal pudendal nerve blocks before vaginal reconstructive and obliterative prolapse procedures (uterosacral ligament suspension, sacrospinous ligament fixation, levator myorrhaphy, or colpocleisis). Women were randomized to one of three study medication groups: 0.9% saline, 0.25% bupivacaine, or combination 0.25% bupivacaine with 4 mg dexamethasone. Our primary outcome was a numeric rating scale pain score on postoperative day 1. Using an analysis of variance evaluated at the two-sided 0.05 significance level, an assumed variance of the means of 0.67, and SD of 1.75, we calculated 21 women per arm to detect a 2-point change on the numeric rating scale (90% power), which we increased to 25 per arm to account for 20% attrition and the use of nonparametric statistical methods. RESULTS: From June 2017 through April 2019, 281 women were screened and 75 (26.7%) were randomized with no differences in baseline demographics among study arms. There was no significant difference in median pain scores on postoperative day 1 among study groups (median [interquartile range] pain score 4.0 [2.0-7.0] for placebo vs 4.0 [2.0-5.5] for bupivacaine vs 4.0 [1.5-5.0] for bupivacaine with dexamethasone, P=.92). CONCLUSION: Preoperative pelvic floor muscle injections and pudendal nerve blocks with bupivacaine and dexamethasone did not improve postoperative pain after vaginal native tissue prolapse procedures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03040011.

Giugale, L. E., et al. (2022). "Total Vaginal Hysterectomy with Uterosacral Ligament Suspension Compared with Supracervical Hysterectomy with Sacrocervicopexy for Uterovaginal Prolapse." Obstetrical and Gynecological Survey 77(3): 151-152.
	
Giulia, B., et al. (2022). "Impact of uterine manipulator on endometrial cancer."
	
Giuseppe, C., et al. (2022). "Systematic lymphadenectomy during interval debulking surgery for advanced epithelial ovarian cancer: A systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
gkbbq, R. B. R. (2022). "Manual therapy in menopausal women suffering from insomnia." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: D035061 The first stage, selection by telephone, will be brief and will serve to verify the menopausal status, interest in joining the study and ask questions for exclusion and inclusion criteria. The questionnaires will also be sent via the telephone application, through a google forms link, so that the first evaluation and session can then be scheduled. The first session will last an average of 2 hours (heart rate variability, assessment and intervention) and the 2nd session, with an interval of two weeks, 1 hour and 30 minutes on average (slightly faster, as there will be no randomization) . In the second stage, face‐to‐face, the participants, who will not know which group they will be allocated to, will provide demographic data and undergo an assessment with heart rate variability, carried out by a properly trained professional. Soon after, they will be randomized into an Experimental Group (osteopathic treatment) or Control Group (sham treatment, with positioning and soft touch) and referred for treatment, which includes assessment and manual therapy techniques, performed by osteopathy students in the 5th year of training. of osteopathy by the Madrid School of Osteopathy and trained by an experienced osteopath. Being the sham treatment for those included in the control group and osteopathic treatment. Each group will be composed of 51 participants, all of whom must be menopausal and have symptoms of insomnia, in addition to residing in Itaúna. In the third stage, the evaluation and intervention will take place in two sessions, and the heart rate variability in decubitus, supine and orthostatism will be evaluated before and after the osteopathic intervention. And in the fourth stage, which is one month after the last service, we will contact the participants by phone and vi CONDITION: D008593 Sleep initiation and maintenance disorders (insomnia) PRIMARY OUTCOME: It is expected to identify osteopathic physiotherapeutic treatment as an effective tool in improving autonomic nervous system function and sleep quality in menopausal women. SECONDARY OUTCOME: To establish a correlation between the worsening of dysautonomia in patients with insomnia and the perceived stress. INCLUSION CRITERIA: The following will be included in the studies: Women with amenorrhea for more than 11 (eleven) months; PSQI (Pittsburgh Sleep Quality Index) score > 5 (greater than five); Participants who voluntarily agree to participate in the study and sign the Free and Informed Consent Form (FICT) for a randomized clinical trial.

Gkegkes Ioannis, D., et al. (2023). "Pancreatic endometriosis: a systematic review." Annals of gastroenterology 36(1): 61-67.
	Background: Extrapelvic manifestations of endometriosis can be identified in nearly every part of the female body, and the true prevalence of extrapelvic locations is unknown. Pancreatic endometriosis may manifest in several ways, ranging from emergency presentations to asymptomatic cysts.; Method: A systematic PubMed and Scopus search was conducted.; Results: Eighteen patients from 17 case reports were included. The patients' mean age was 39.3 (range: 21-72) years. An emergency presentation was noted in 8 of the 18 (44.4%) patients. Menstrual irregularity was present in 3 (16.7%) patients, while in 3 (16.7%) cases there was simultaneous presence of endometriosis elsewhere. The most frequent symptoms at presentation of pancreatic endometrial cysts were epigastric pain, acute left upper quadrant pain, back pain, nausea/vomiting/diarrhea, which occurred in 12 (66.7%), 11 (61.1%), 4 (22.2%), and 6 (33.3%) patients, respectively. Only one case presented as an asymptomatic pancreatic cyst. The maximum diameter of the endometrial cysts ranged from 1-16 cm. In the majority of cases, surgical treatment was offered (16/18, 88.9%). Recurrence of pancreatic endometrial cyst occurred in one case only, following needle aspiration of the endometrial cyst. No fatality was reported.; Conclusions: Review of the available published literature suggests that pancreatic endometriosis is a rare condition that should be included in the differential diagnosis of pancreatic masses. Further clinical and experimental studies are necessary to investigate the pathogenesis of extrapelvic and pancreatic endometriosis.; Competing Interests: Conflict of Interest: None (Copyright: © Hellenic Society of Gastroenterology.)

Gkrozou, F., et al. (2022). "Endometrial Cancer Following Endometrial Ablation: An Overview of Published Literature." Indian Journal of Gynecologic Oncology 20(2): 26.
	Purpose: This study is an evaluation of the long-term risk of endometrial cancer in patients undergoing EA with first- and second-generation ablative techniques. A variety of different endometrial ablation devices developed, with complication rate lower than the hysteroscopic resection. The incidence of endometrial cancer has risen by 57% in the last 20 years worldwide. More than 90% of patients will present with postmenopausal bleeding as the most common red flag symptom for endometrial cancer. A reasonable assumption is that through destruction of the endometrium, the incidence of endometrial cancer after EA should be reduced. However, there are concerns raised regarding intrauterine scarring and distortion of the uterine cavity after EA, which may delay the diagnosis of endometrial cancer. Method(s): For this narrative review, four major search engines were explored (MEDLINE, Google Scholar, PubMed and EMBASE) up to December 2021, to retrieve articles that provide information about on incidence of endometrial cancer after endometrial ablation. Result(s): Thirty-two cases have been identified and studied. This study has confirmed that 76.5% of endometrial cancer cases after EA were diagnosed at stage I, which is consistent with the evidence from the literature. It has also showed that endometrial ablation does not delay the diagnosis of endometrial cancer. Conclusion(s): All clinicians need to maintain high degree of suspicion and thus offer in-depth counselling to their patients. Patient selection is important, and thus, ablation should be offered only to women preferable without risk factors, along with a recent normal endometrial biopsy.Copyright © 2022, The Author(s) under exclusive licence to Association of Gynecologic Oncologists of India.

Gkrozou, F., et al. (2021). "Tubo-ovarian abscess: Exploring optimal treatment options based on current evidence." Journal of Endometriosis and Pelvic Pain Disorders 13(1): 10-19.
	Purpose: Tubo-ovarian abscess (TOA) and pelvic abscess are characterized by an inflammatory pelvic mass. In the majority of cases, this condition involves the ovaries, the fallopian tubes and/or any other adjacent tissue. TOA is considered a severe complication of PID and can cause severe sepsis. The main risk factors for women's health are the size of the abscess, the initial amount of white blood cells (WBC), patients' age as well as, any co-existing comorbidities. Method(s): This study provides a review of the current literature regarding the management of TOA and the different criteria used in order to establish the optimal therapeutic approach or to predict outcome by individualizing cases. Four major search engines, MEDLINE, Google Scholar, PubMed and EMBASE, up to February 2020 were explored, focusing in epidemiology and risk factors, pathogenesis, diagnosis and treatment. Result(s): Our review suggests that there are no clear guidelines for best practice, in case of TOA, but it appears that intravenous antibiotics combined with interventional radiology have good results for TOA <5 cm. When TOA is >5 cm, laparoscopic approach is indicated. Further studies are needed in order to evaluate the best treatment for women with TOA. Conclusion(s): More prospective studies on large-series of patients are in need, in order to determine a clear pathway and to suggest specific criteria, which can guide clinicians to choose optimal approach in a timely manner.Copyright © The Author(s) 2020.

Glanville Elizabeth, J., et al. (2022). "A randomized trial of endometrial scratching in women with PCOS undergoing ovulation induction cycles." Reproductive Biomedicine Online 44(2): 316-323.
	Research Question: Does endometrial scratching improve the chance of a live birth in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction and trying to conceive?; Design: An international, multicentre, randomized, sham-controlled trial across six fertility clinics in three countries (New Zealand, UK and Brazil). Women with a diagnosis of PCOS who were planning to commence ovulation induction cycles (at least three cycles) in order to conceive were randomly assigned to receive the pipelle (scratch) procedure or a sham (placebo) procedure in the first cycle of ovulation induction. Women kept a diary of ovulation induction and sexual intercourse timing over three consecutive cycles and pregnancies were followed up to live birth. Primary outcome was live birth and secondary outcomes were clinical pregnancy, ongoing pregnancy, multiple pregnancy, adverse pregnancy outcomes, neonatal outcomes, bleeding following procedure and pain score following procedure.; Results: A total of 117 women were randomized; 58 to the scratch group and 59 to the sham group. Live birth occurred in 11 (19%) women in the scratch group and 14 (24%) in the sham group (odds ratio 0.76, 95% confidence interval [CI] 0.30-1.92). Secondary outcomes were similar in each group. Significantly higher pain scores were reported in the scratch group (adjusted mean difference 3.2, 95% CI 2.5-3.9) when measured on a visual analogue scale.; Conclusion: No difference was detected in live birth rate for women with PCOS who received an endometrial scratch when trying to conceive using ovulation induction; however, uncertainty remains due to the small sample size in this study. (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Gleason, C. E., et al. (2024). "Long-term cognitive effects of menopausal hormone therapy: Preliminary data from the KEEPS Continuation Study." Journal of Neurosurgical Anesthesiology 36(1): 1258.
	Objective: Findings from the Kronos Early Estrogen Prevention Study (KEEPS)- Cog trial suggested no cognitive benefit or harm after 48 mos of early postmenopause hormone therapy (HT) taken in early menopause. Long-term effects of early menopausal HT are understudied. The KEEPS-Continuation reevaluated cognition, mood, and neuroimaging effects in KEEPS women, ~10 yrs after randomization (~6 yrs after trial completion). Preliminary cognitive findings are presented here. Design(s): Women enrolled in KEEPS were randomized to placebo or HT [oral conjugated equine estrogens (oCEE+progesterone) or transdermal 17-beta-estradiol (tE2+progesterone)] for 48mos. After ~10 yrs (M(SD)=9.57(1.08) yrs), KEEPS-Continuation assessed long-term HT effects. Cognitive tests from KEEPS and KEEPS-Continuation were analyzed as 4 factor scores. Because KEEPS-Continuation visits occurred 8-14 yrs post-randomization, Linear latent growth models (LGM) with distal outcomes, tested whether baseline cognitive performance and change-in-cognition across KEEPS visits predicted "distal" KEEPS-Cognition cognition, and whether HT randomization modified this relationship. Covariates included education, age, and APOEe4 carrier status. LGMs summary fit measures were assessed along with residuals for mean and covariance. Result(s): Of KEEPS enrollees, N=299 (41%) participated in KEEPS-Continuation. Similar health characteristics were observed at randomization for participants (agemean=65.8; range: 56-71) and non-participants (i.e. women not enrolled in KEEPS-Continuation). For women in the KEEPS-Continuation, cognitive performance was not influenced by either HT formulation. Instead, models showed strong associations between baseline and changein- cognition during KEEPS and the same measures in KEEPS-Continuation (Table 1); i.e., strongest predictor of cognitive performance in KEEPS-Continuation was cognitive performance in KEEPS. KEEPS-Continuation cross-sectional comparisons confirmed that both HT-groups performed similarly to placebo on cognitive measures. Conclusion(s): Preliminary KEEPS-Continuation analyses detected no long-term cognitive effects of shortterm (48mos) menopausal HT vs placebo. Subsequent analyses will examine the influence of HT vs. placebo on mood and amyloid PET, and non-randomized use of HT post KEEPS on all outcomes. These data provide important information for recently menopausal women with good cardiovascular health considering HT for menopausal symptoms. (Table Presented).

Gluck, O., et al. (2023). "The Effect of Preemptive Local Infiltration on Postoperative Pain After Vaginal Hysterectomy: A Retrospective Study." Journal of Minimally Invasive Gynecology 30(4): 308-311.
	Study Objective: To investigate the effect of preemptive infiltration on postoperative pain and the use of analgesics after vaginal hysterectomy (VH). Design(s): A retrospective study. Setting(s): An urogynecology unit in a tertiary medical center. Patient(s): A total of 120 patients who had undergone VH. Intervention(s): The study group contained 60 patients who participated in a former randomized control study, in which preemptive local infiltration of bupivacaine (n = 30) or sodium chloride 0.9% (n = 30) was performed. The control group included 60 consecutive patients who underwent a VH, for whom no local infiltration was performed. Measurements and Main Results: Postoperative pain at rest was assessed using the 10 cm visual analog scale at 3, 8, and 24 hours after surgery. The levels of pain, as well as the use of analgesics, postoperatively, were compared between the groups. The mean surgery length in the infiltration group was shorter (86.4+/-29 vs 118.6+/-30, p <.001) and the rate of posterior colporrhaphy was lower (73.1% vs 91.3%, p = .010) than the control group. There were no differences in levels of pain at all points of time. However, the infiltration group required a lower morphine dose in the recovery unit (3.7 +/- 2.3 mg vs 5.3 +/- 2.4 mg, p <.001) and less use of analgesia (all kinds) 24 hours after surgery (54.2% vs 79.6%, p <.001) compared with the control group. On multivariant analysis, preemptive infiltration was found to be independently inversely associated with the dose of morphine used in recovery, as well as analgesics used 24 hours after surgery. Conclusion(s): Preemptive local infiltration of either bupivacaine or sodium chloride 0.9% reduced the use of morphine in the recovery unit, as well as the use of analgesics 24 hours after VH, compared with no infiltration at all.Copyright © 2022 AAGL

Gluck, O., et al. (2021). "The effect of preemptive local anesthesia on postoperative pain following vaginal hysterectomy: a randomized controlled trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 267: 269‐273.
	OBJECTIVE: We aimed to study the effect of preemptive local anesthetic without adrenaline on postoperative pain following vaginal hysterectomy and concomitant trans obturator tape (TOT). STUDY DESIGN: This was a double‐blinded, randomized, controlled trial. Women who undergone elective vaginal hysterectomy were included. Solutions of either Bupivacaine‐Hydrochloride 0.5%, or Sodium‐Chloride 0.9% as a placebo, were prepared prior to surgery, according to randomization. The chosen solution was injected before incision, in a circumferential manner, to the cervix. The amount of fluid administered was 10 ml. When colporrhaphy was also performed, an additional 5 ml of solution were injected in the midline of the vaginal wall prior to each incision line. We conformed to the CONSORT recommendations. By utilizing the 10 cm Visual‐analogue‐scale (VAS) we assessed post‐operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. We estimated that the intervention would cause a 25% reduction in the primary outcome. The required total sample size was calculated to be 30 patients women for each group. We used ANOVA for continuous variables and the Chi‐square or Fisher exact tests for categorical variables. RESULTS: A total of 30 women were included in each group. The level of postoperative pain, as assessed by VAS, was not significantly different between the groups, in all points of time. In addition, there was no difference between the groups in opioid based analgesics during recovery, nor in postoperative analgesic use. CONCLUSION: Preemptive local anesthesia was not shown to be efficient in reducing postoperative pain after vaginal hysterectomy and TOT.

Gmb, H. A. G. O. R. and GlaxoSmithKline (2023). Study to Estimate Efficacy of Combining Dostarlimab and Niraparib in Relapsed EOC After Treatment With PARPi.
	No Results Available Drug: Niraparib|Drug: Dostarlimab Objective Response Rate (ORR)|Response Rate|Median Progression Free Survival (PFS)|6 months Progression Free Survival (PFS) rate|Disease Control Rate (DCR)|Overall Survival (OS)|Time from registration to start of first subsequent therapy (TFST) Female Phase 2 100 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment AGO-OVAR 2.35|2021-003572-14 November 1, 2026

Gmb, H. E. H. (2024). Pilotstudie Zur Untersuchung Des Effektes Einer Dysmenorrhoe-App.
	No Results Available Device: Pia-App Dysmenorrhea Symptom Interference Scale (DSI)|Moos Menstrual Distress Questionnaire, Form C (MDQ)|Visuelle Analogskala Schmerz (VAS)|Depression Anxiety Stress Scale mit 21 Items (DASS-21)|Fragebogen zur Erfassung der schmerzspezifischen Selbstwirksamkeit (FESS)|Fatigue Severity Scale (FSS)|Pain Disability Index (PDI) Female Not Applicable 100 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Supportive Care RCT004_PilotPia July 2024

Gmb, H. p. (2021). CATCH-R: A Rollover Study to Provide Continued Access to Rucaparib.
	No Results Available Drug: Rucaparib Safety follow-up All Phase 3 34 Industry Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CO-338-111|2020-001538-37 March 8, 2023

Gnanachandran, C., et al. (2023). "Myomectomy Benefits, Risks, Long-Term Outcomes, and Effects on Fertility and Pregnancy Outcomes: A Literature Review." Journal of Gynecologic Surgery 39(4): 151-157.
	Objective: Abdominal myomectomy is the mainstay for women with intramural fibroids who want to conceive. Informed choice, discussion on alternatives, and consent for surgery are essential prior to the procedure. Women with fibroids need to understand the potential long-term complications and future implications, including the effects of fibroids or myomectomy on fertility and pregnancy outcomes. This article offers evidence-based information for informing women about the consequences and benefits of myomectomy and other treatments. Method(s): Using thesaurus terms, articles in English since 2012, on PubMed, Embase (OVID), and MEDLINE (ProQuest) databases were retrieved via the National Institute for Health and Care Excellence Healthcare Databases Advanced Search interface. Myomectomy outcomes, risks, complications, fertility, and rare complications later in pregnancy were reviewed. Result(s): Ninety-two articles were chosen. They covered topics relevant to this review. Duplicate articles, those not related to this review, or with low numbers of cases in retrospective studies were excluded. When fibroids affect reproductive age women, myomectomy's surgical and reproductive outcomes have significant benefits, compared to relatively severe but uncommon complications. Myomectomy-related long-term reintervention is higher than for hysterectomy, but short-term outcomes for pain and bleeding are comparable to hysterectomy. Conclusion(s): Myomectomy (laparoscopic or open) is safe. Benefits are greatest for reproductive-age women with fibroids. Surgical and reproductive outcomes of myomectomy have benefits, compared to relatively few severe but uncommon complications. This review article of all the potential benefits, risks, and complications can help surgeons inform patients appropriately and reduce potential litigation. (J GYNECOL SURG 39:151)Copyright © Mary Ann Liebert, Inc.

Godiwala, P., et al. (2024). "The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: a sibling oocyte double-blinded prospective randomized clinical trial." Fertility and Sterility 122(1): 85-94.
	OBJECTIVE: To compare the euploidy rates among blastocysts created from sibling oocytes injected with sperm and processed using microfluidics or density gradient centrifugation. DESIGN: Sibling oocyte randomized controlled trial. SETTING: Single university-affiliated infertility practice. PATIENTS: A total of 106 patients aged 18-42 years undergoing fresh in vitro fertilization treatment cycles with preimplantation genetic testing between January 2021 and April 2022 contributed 1,442 mature oocytes, which were injected with sperm and processed using microfluidics or density gradient centrifugation. INTERVENTION(S): The sperm sample is divided and processed using a microfluidics device and density gradient centrifugation for injection into sibling oocytes. MAIN OUTCOME MEASURE(S): The primary outcome was the embryo euploidy rate. Secondary outcomes included fertilization, high-quality blastulation, and ongoing pregnancy rates. RESULT(S): The blastocyst euploidy rate per mature oocyte was not significantly different in the study group compared with the control group (22.9% vs. 20.5%). The blastocyst euploidy rate per biopsied embryo was also similar between the 2 groups (53.0% vs. 45.7%). However, the fertilization rate per mature oocyte injected was found to be significantly higher in the study group compared with the control group (76.0% vs. 69.9%). The high-quality blastulation rate per mature oocyte injected was similar between the 2 groups, as was the total number of embryos frozen. There were no differences in the number of participants with no blastocysts for biopsy or the number of participants with no euploid embryos between the 2 groups. Among the male factor infertility and recurrent pregnancy loss subgroups, there were no differences in euploidy rates, fertilization rates, blastulation rates, or total numbers of blastocysts frozen, although the study was underpowered to detect these differences. Seventy-seven patients underwent frozen embryo transfer; there were no significant differences in pregnancy outcomes between the 2 groups. CONCLUSION(S): Microfluidics processing did not improve embryo euploidy rates compared with density gradient centrifugation in this sibling oocyte study, although fertilization rates were significantly higher. CLINICAL TRIAL REGISTRATION NUMBER: NCT04744025.

Goel, V., et al. (2023). "The Comparative Analysis of the Effectiveness of Inj. Methotrexate and Tab Mifepristone vs Inj. Methotrexate alone in the Medical Management of Ectopic Pregnancy." Journal of Cardiovascular Disease Research 14(8): 2201-2208.
	Background: Recent trends in ectopic pregnancy morbidity and the percentage of young, childless patients make it critical to identify EP early to save patients' lives and preserve their fertility to the fullest extent possible. The most commonly used conservative therapies are methotrexate and mifepristone, but it is impossible to determine which treatment is superior. Aim and Objective: The Comparative Analysis of the Effectiveness of Inj. Methotrexate and Tab Mifepristone vs Inj. Methotrexate alone in the Medical Management of Ectopic Pregnancy. Material(s) and Method(s): This was a randomized control trial. Patients with a progressing ectopic pregnancy meeting criteria for medical management were included in the study. Patients were assigned to two groups based on random selection. Group 1 was given a combination of 200 mg of Tab mifepristone and inj. Methotrexate IM (50 mg/m2). Group 2 received only injections of methotrexate. The dose of methotrexate was repeated depending on the individual patient's response. Results and Conclusion(s): In terms of success rate and the requirement for a second dosage of methotrexate, there was no statistically significant difference between the two groups. However, employing a combination therapy instead of just methotrexate for medical care resulted in a quicker resolution of the ectopic pregnancy and a shorter hospital stay. p=0.002275.Copyright © 2023 EManuscript Technologies. All rights reserved.

Goenka, L., et al. (2022). "Use of "Repurposed" Drugs in the Treatment of Epithelial Ovarian Cancer: A Systematic Review." American Journal of Clinical Oncology 45(4): 168-174.
	Epithelial ovarian cancer has poor outcomes with standard therapy and limited options for treatment of recurrent disease. This systematic review summarizes the data on the clinical use of repurposed drugs. We searched for clinical studies using "repurposed" agents for the treatment of ovarian cancer in the following databases: PubMed, clinicaltrials.gov, Clinical Trial Registry of India, European Clinical Trials Registry, and Chinese Clinical Trial Registry. We excluded reviews, preclinical studies, and non-English language studies. We assessed the quality of included studies. The following agents/class of agents were included: statins, hydroxychloroquine, metformin, itraconazole, nonsteroidal anti-inflammatory drugs, vitamin D, proton pump inhibitors, beta-blockers, and sodium valproate. Only one randomized controlled trial investigated metformin, which found no benefit of metformin. However, this had a high risk of bias (no details of randomization). Among the observational studies, 70% were of high quality (Newcastle-Ottawa scale ≥7). Clinical benefit was seen for itraconazole, beta-blockers, metformin, statins, and proton pump inhibitors. Though multiple studies aim to repurpose agents in epithelial ovarian cancer, the most published literature is observational, and none are practice-changing. Given the solid preclinical data regarding the anticancer efficacy of these agents, well-designed clinical trials are urgently required.; Competing Interests: The authors declare no conflicts of interest. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Goitia, M. and J. Estadella (2023). "[Emerging therapies in the medical treatment of uterine fibroids]." Medicina clinica 161 Suppl 1: S32-S37.
	
Goje, O., et al. (2021). "Outcomes of Minimally Invasive Management of Tubo-ovarian Abscess: A Systematic Review." Journal of Minimally Invasive Gynecology 28(3): 556-564.
	Objective: To compare the success rate, complications, and hospital length-of-stay of 3 modalities of minimally invasive management of tubo-ovarian abscesses (TOAs): laparoscopy, ultrasound-guided drainage, and computed tomography-guided drainage.; Data Sources: Electronic-based search in PubMed, EMBASE, Ovid MEDLINE, Google Scholar, and Cochrane Central Register of Controlled Trials, using the following Medical Subject Heading terms: "minimally invasive surgical procedures," "drainage," "abscess," "tubo-ovarian," "ovarian diseases," and "fallopian tube diseases."; Methods of Study Selection: Of the 831 articles in the initial results, 10 studies were eligible for inclusion in our systematic review.; Tabulation, Integration, and Results: A total of 975 patients were included in our study; 107 (11%) had laparoscopic drainage procedures, and 406 (42%) had image-guided (ultrasound or computed tomography) drainage of TOAs. Image-guided TOA drainage had higher success rates (90%-100%) than laparoscopic drainage (89%-96%) and the use of antibiotic treatment alone (65%-83%). Patients treated with image-guided drainage had no complications (for up to 6 months of follow-up) and shorter lengths of hospital stay (0-3 days on average) compared with laparoscopic drainage (5-12 days) or conservative management with antibiotics alone (7-9 days).; Conclusion: Although conservative management of TOAs with antibiotics alone remains first-line, our review indicates that better outcomes in the management of TOA were achieved by minimally invasive approach compared with conservative treatment with antibiotics only. Of the minimally invasive techniques, image-guided drainage of TOAs provided the highest success rates, the fewest complications, and the shortest hospital stays compared with laparoscopy. The low magnitude of evidence in the included studies calls for further randomized trials. This systematic review was registered in the International Prospective Register of Systematic Review (register, http://www.crd.york.ac.uk/PROSPERO;CRD 42020170345). (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Goje, O., et al. (2023). "Oral Ibrexafungerp for Vulvovaginal Candidiasis Treatment: An Analysis of VANISH 303 and VANISH 306." Journal of women's health (2002) 32(2): 178-186.
	Background: Ibrexafungerp is a novel antifungal treatment for acute vulvovaginal candidiasis (VVC). Using pooled data from two phase three studies (VANISH 303 and 306) in the treatment of acute VVC, this analysis sought to determine the effectiveness of ibrexafungerp in various patient subgroups that may impact outcomes. Materials and Methods: Data from VANISH 303 (NCT03734991) and VANISH 306 (NCT03987620) evaluating ibrexafungerp 300 mg twice daily (BID) for 1 day versus placebo, were pooled and analyzed to determine clinical cure rate, clinical improvement, and mycological cure at the test-of-cure visit (day 11 ± 3) and symptom resolution at the follow-up visit (day 25 ± 4) in the overall population. Patient subgroups analyzed included race, body mass index (BMI), baseline vulvovaginal signs and symptoms (VSS) score, and Candida species. Results: At the test-of-cure visit, patients receiving ibrexafungerp, compared with those who received placebo, had significantly higher rates of clinical cure (56.9% [214/376 patients] vs. 35.7% [65/182 patients]), clinical improvement (68.4% [257/376 patients] vs. 45.1% [82/182 patients]), and mycological cure (54.0% [203/376 patients] vs. 24.2% [44/182 patients]; all p < 0.0001). At the follow-up visit, patients receiving ibrexafungerp had sustained responses with higher symptom resolution rates (66.8% [251/376 patients]) versus placebo (48.4% [88/182 patients]; p < 0.0001). Race, BMI, baseline VSS score (including VSS severity score 13-18), and Candida species infection did not adversely affect clinical cure rates. Safety analysis results were consistent with the individual studies. Conclusions: Ibrexafungerp provides a safe and well-tolerated first-in-class fungicidal, 1-day oral treatment for patients with acute VVC, the first new therapy in >20 years. Clinical Trial Registration Number: NCT03734991.

Goje, T., et al. (2022). "Outcomes in Subpopulations from Pooled Phase 3 Clinical Studies of Oral Ibrexafungerp Versus Placebo in Patients with Vulvovaginal Candidiasis (VANISH 303 and 306)." American Journal of Obstetrics and Gynecology 226(2): 290.
	Objectives: In the United States (US), there are approximately 10 million office visits annually for vaginal symptoms, of which approximately 20-25% are vulvovaginal candidiasis (VVC). The current approved therapies for treatment of VVC are all azoles which are fungistatic. Here, we introduce oral ibrexafungerp (IBX), a novel triterpenoid antifungal, with fungicidal activity against a broad range of Candida species for treatment of VVC. The purpose of this research is to examine efficacy and safety; and subpopulation outcomes from two phase 3 clinical trials of oral IBX versus Placebo (PLC) in patients with vulvovaginal candidiasis (VVC) in a pooled analysis Methods: Two randomized, double-blind, placebo-controlled clinical trials of IBX were conducted in patients with VVC, (VANISH 303 and 306). VANISH 303 enrolled patients in the United States (US) and VANISH 306 in the US and Bulgaria. Inclusion criteria were: females with vaginal sign and symptoms (VSS) >=4 at baseline, age >=12 years, potassium hydroxide (KOH)-positive microscopy. Patients were randomized 2:1 to receive IBX 300 mg BID for one day for a total treatment dosage of 600 mg or matching PLC. The primary endpoint was the percentage of patients with clinical cure (complete resolution of VSS=0) at the test-of-cure (TOC) (day 11+/-3) visit. Data from both studies were pooled, and key subgroups of interest analyzed. Result(s): 376 patients receiving IBX and 182 patients receiving placebo were included in the pooled modified intent-to-treat (mITT) analysis. Overall, IBX demonstrated superiority over PLC in the primary endpoint of clinical cure at TOC, 56.9% vs. 35.7% respectively (p<0.001), Clinical cure at TOC in sub-populations for IBX were as follows: in patients aged <65, 57.0% (n=374), in Black patients, 52.3% (n=107), in Hispanic or Latino patients, 54.7% (n=75), in patients with BMI >35, 46.2% (n=65). IBX was generally well-tolerated, with Treatment-Emergent Adverse Events (TEAEs) reported in >=5% of IBX-treated patients including diarrhea (16.7%), nausea (11.9%), and abdominal pain (8.3%), the majority were mild to moderate in nature, lasting 1 day. Conclusion(s): This analysis shows the efficacy and safety of IBX, a fungicidal anti-fungal in the treatment of VVC, and in relevant sub-populations. If approved, oral IBX will provide the first new non-azole option for clinicians to prescribe to their patients suffering from VVC.Copyright © 2021

Gök, S. and E. Alataş (2022). "Effects of Levonorgestrel-Releasing Intrauterine Device Therapy on Ovarian Reserve in Menorrhagia." Cureus 14(11): e31721.
	Objective This study aimed to investigate the effects of levonorgestrel-releasing intrauterine device (LNG-IUD) treatment on ovarian reserve in women of reproductive age diagnosed with menorrhagia. Methods This was a prospective controlled trial involving 50 women with menorrhagia and a control group comprising age-matched 50 healthy women. Women who satisfied the LNG group criteria underwent an endometrial pipelle biopsy and LNG-IUD insertion. Ovarian reserve tests were performed prior to and six months after LNG-IUD insertion in the LNG group cases. Results Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), endometrial thickness (ET), total antral follicle count (AFC), and mean ovarian volume values before LNG-IUD insertion did not differ between the LNG and control groups. When the final measurements were compared, FSH, AMH, total AFC, and average ovarian volume increased (p=0.05, 0.046, 0.022, and 0.022, respectively), E2 and ET decreased (p=0.034 and 0.001, respectively) in the LNG group, while LH did not differ significantly between the groups (p=0.71). Conclusion We observed that LNG-IUD use effectively improves fertility capacity. In this study, LNG-IUD use in reproductive-age women diagnosed with menorrhagia decreased E2 levels, did not change LH levels, and increased FSH, AFC, and AMH levels.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Gök et al.)

Gökbulut, N., et al. (2022). "The impact of foot massage given to postmenopausal women on anxiety, fatigue, and sleep: a randomized-controlled trial." Menopause (New York, N.Y.) 29(11): 1254-1262.
	Objective: This study aims to determine the impact of foot massage given to postmenopausal women on anxiety, fatigue, and sleep.; Methods: This randomized-controlled study was conducted with 70 women (35 experimental, 35 control) who resided in a village located in Northern Turkey. In the study, the women in the experimental group were given foot massage once every day for 7 days. No intervention was applied to the women in the control group. The data were collected using a Personal Information Form, the Fatigue Severity Scale (FSS), and the Beck Anxiety Inventory (BAI) Descriptive statistics (frequency, percentage distribution, median, and Q1-Q3), χ 2 test, Mann-Whitney U test, and Wilcoxon test were used in the analysis of the data.; Results: It was found that the women in the control group had lower pretest BAI scores than those in the experimental group ( P < 0.05), whereas before the foot massage intervention, the women in the experimental and control groups had similar FSS scores and sleep hours ( P > 0.05). After the foot massage, the FSS scores were 2.3 (1.6-3.4) in the experimental group and 5.5 (4.6-6.2) in the control group, the BAI scores were 26.0 (23.0-29.0) in the experimental group and 36.0 (31.0-43.0) in the control group, the daily sleep hours were 8.0 (8.0-10.0) in the experimental group and 7.0 (6.0-8.0) in the control group, and the differences between the groups were statistically significant ( P < 0.001).; Conclusions: It was determined that foot massage applied during menopause increases the average daily sleep duration (hours) and reduces women's fatigue and anxiety levels.; Competing Interests: Financial disclosures/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Gold, M. H., et al. (2023). "Improvements in Skin Quality Parameters in Postmenopausal Participants After Use of Topical Growth Factor Serum." Journal of cosmetic dermatology 22(1): 236‐244.
	BACKGROUND: Photodamage can induce skin aging processes that can be particularly concerning for postmenopausal women. Growth factors from hypoxic human fibroblast‐conditioned media have demonstrated improvements in skin quality parameters. AIMS: The aim of the study was to assess efficacy and tolerability of topical combination‐treatment hypoxic growth factor serum (TNS A+) in postmenopausal women with moderate to severe facial photodamage. PATIENTS/METHODS: In this 12‐week, open‐label, single‐center study, participants used TNS A+ serum twice daily. Postmenopausal women (40‐65 years of age) with Fitzpatrick skin types I‐VI and modified Griffiths scale scores 4‐9 were eligible. Clinical and participant‐reported assessments were evaluated at Weeks 6 and 12. Statistical significance was defined as p ≤ 0.05. RESULTS: There were 17 enrolled participants. TNS A+ treatment demonstrated significant improvements from baseline in fine lines and wrinkles in periocular, forehead, and cheek areas at Week 12 and the perioral area at Weeks 6 and 12. Significant improvements from baseline in coarse lines and wrinkles were observed for the perioral area at Week 12 and periocular and cheek areas at Weeks 6 and 12. Improvements in overall photodamage, skin tone evenness, and tactile roughness were significantly greater at Weeks 6 and 12 versus baseline. Most participants reported TNS A+ made their skin look and feel smooth, soft, and rejuvenated; improved skin radiance; made lines and wrinkles less apparent; and improved skin texture. No treatment‐related adverse events were reported. CONCLUSIONS: The TNS A+ regimen was well tolerated and provided significant improvements in skin quality in postmenopausal women with moderate to severe facial photodamage.

Goldberg Rebecca, M., et al. (2022). "Secondary cytoreductive surgery for recurrent low-grade serous ovarian carcinoma: A systematic review and meta-analysis." Gynecologic Oncology 164(1): 212-220.
	Objectives: Low-grade serous ovarian cancer (LGSC) is a relatively chemo-resistant disease with limited effective treatment options for patients with recurrence. Secondary cytoreductive surgery (SCS) is commonly offered at recurrence, although any benefit this has on survival is not fully determined. This review evaluates the impact of SCS, including residual disease, on progression-free survival (PFS) and overall survival (OS) in recurrent LGSC.; Methods: A comprehensive search of Medline ALL, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science was conducted to obtain studies evaluating optimal or complete SCS versus suboptimal SCS and the amount of residual disease in recurrent LGSC. Meta-analysis was performed and PFS and OS outcomes were calculated.; Results: 1Of 5296 studies screened, 350 progressed to full-text review, with 9 ultimately selected for inclusion in the systematic review. Two studies met criteria for meta-analysis of PFS and of OS. The presence of visible residual disease at the conclusion of SCS negatively impacted PFS (HR = 3.51, 95% CI = 1.72-7.14), whereas SCS with no residual disease significantly improved OS (HR = 0.4, 95% CI = 0.23-0.7) in patients with recurrent LGSC. Diffuse and extensive disease distribution was inversely linked to survival. In addition, SCS as an initial treatment for recurrent LGSC was associated with superior survival in comparison to chemotherapy. A short platinum-free interval was not associated with worse survival in this cohort.; Conclusions: Complete SCS, and to a lesser extent optimal SCS, are associated with improved PFS and OS in patients with recurrent LGSC. SCS may be a better initial treatment strategy than systemic chemotherapy for recurrent disease. Patients with recurrent LGSC should be evaluated for the role of SCS based on disease distribution and functional status, irrespective of the platinum-free interval. Prospective studies are needed to further study the role of SCS in patients with recurrent LGSC.; Competing Interests: Declaration of Competing Interest The authors have no conflict of interests to declare. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Goldman, A. R., et al. (2021). "Transcutaneous Electrical Nerve Stimulation to Reduce Pain With Medication Abortion: a Randomized Controlled Trial." Obstetrics and Gynecology 137(1): 100‐107.
	OBJECTIVE: To evaluate whether high‐frequency transcutaneous electrical nerve stimulation (hfTENS) reduces pain during medication abortion. METHODS: We conducted a randomized, placebo‐controlled trial. Participants who were undergoing medication abortion with mifepristone and misoprostol through 70 days of gestation either received active 80 Hz hfTENS or sham to use for a minimum of 60 minutes within 8 hours of misoprostol. Maximum pain on an 11‐point numerical rating scale at 8 hours after misoprostol was the primary outcome. We estimated 20 per group for 80% power to detect a 2‐point difference and up to 10% attrition. Secondary outcomes included a maximum pain score at 24 hours, additional analgesia use, the difference in score before and after treatment, the experience of side effects, abortion outcomes, and acceptability. We collected data at baseline, time of misoprostol (0‐hour), 8‐hour and 24 hours using real‐time electronic surveys, and at follow‐up. RESULTS: Between June 2019 and March 2020, we screened 251 patients and randomized 40‐20 each to hfTENS or sham‐with one postrandomization exclusion and two patients lost to follow‐up. Baseline characteristics were similar. Median maximum pain scores at 8 hours were 7.0 (interquartile range 3.0) and 10.0 (interquartile range 3.0) for hfTENS and sham, respectively. The distribution of these scores was lower among hfTENS users compared with sham (mean rank 15.17 vs 22.63, P=.036). High‐frequency TENS users also experienced a significant reduction in posttreatment pain score (‐2.0 [interquartile range 2.5] vs 0 [interquartile range 1.5], P=.008). We found no statistically significant differences in use of additional analgesia, distribution of maximum pain scores at 24 hours, side effects, or measures of acceptability. CONCLUSION: High‐frequency TENS reduced maximum pain scores within 8 hours of misoprostol and reduced pain scores immediately after treatment compared with placebo. High‐frequency TENS offers an effective nonpharmacologic option for pain management during medication abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03925129.

Goldštajn Marina, Š., et al. (2023). "Effects of transdermal versus oral hormone replacement therapy in postmenopause: a systematic review." Archives of Gynecology and Obstetrics 307(6): 1727-1745.
	Purpose: To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women.; Methods: We performed a systematic review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer.; Results: The systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route.; Conclusions: Available evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route. (© 2022. The Author(s).)

Goldstein, A., et al. (2023). "Phase II Study of AbobotulinumtoxinA in Patients with Provoked Vestibulodynia: Outcomes From Dose-finding Stage." Journal of Sexual Medicine 20(Supplement 2).
	Introduction Vulvodynia is associated with significant burden and impaired quality of life and affects up to 28% of women of reproductive age. The most common subtype is provoked vestibulodynia (PVD), in which pain is localized and triggered by vestibular contact. Treatment options are limited; no therapy is approved for PVD. Hypertonicity of the pelvic floor muscles is a common factor associated with PVD; therefore, patients may benefit from treatments that relax the pelvic floor. BotulinumtoxinA is used for prolonged muscle relaxation across multiple conditions. Current clinical data in patients with PVD are inconclusive, but off-label anecdotal use suggests benefit. Objective To assess the safety, efficacy, and optimal dosing of abobotulinumtoxinA (aboBoNT-A) for the treatment of PVD and explore the utility of a novel endpoint for pain assessment in PVD. Methods This phase II, randomized, placebo-controlled study (NCT03598777) comprised two steps: dose escalation (stage 1) and dose expansion (stage 2). Stage 1 included up to four treatment cycles; cycle 1 was double-blind, while cycles 2-4 were open-label. Patients were assessed for retreatment every 6 weeks. Enrolled premenopausal, adult women with PVD associated with pelvic-floor hypertonia were randomized 4:1 to receive aboBoNT-A (100 units [U] [n=8], 300 U [n=8], 400 U [n=14], and 500 U [n=17]) or placebo (n=13). A new efficacy endpoint was introduced, combining the use of eight vaginal dilators of increasing diameter and patient-reported pain in response to dilator insertion on an 11-point numeric rating scale (NRS) to derive a composite pain score. Based on the subjective pain threshold, the largest-sized dilator that the patient accepted was defined as the dilator maximum tested size (DMTS). Results Patients (aged 19-45 years; mean, 29.4 years) received aboBoNT-A or placebo. Baseline demographics and disease characteristics were well-balanced across treatment groups. All treatment-emergent adverse events (TEAEs) were mild or moderate. Among aboBoNT-A-treated patients, urinary incontinence occurred in one patient in cycle 1, one patient in cycle 2, and two patients in cycle 3. During cycle 1, treatment-related TEAEs occurred in patients receiving aboBoNT-A 500 U or placebo (3/17 patients and 1/13 patients, respectively), with none reported for doses <500 U. In terms of composite score for dilator test, there was a numerical trend for benefit with aboBoNT-A 300 U and a trend for increasing benefit with increasing number of injections. All women who received at least three active treatment cycles with aboBoNT-A had a decrease in dilator-induced pain from baseline of >=30% and >=2 points at week 6, as reported on the 11-point NRS. Efficacy and validity of the DMTS were not statistically analyzed owing to the sponsor's decision to discontinue the trial (for reasons unrelated to efficacy or safety). Conclusions AboBoNT-A showed an acceptable safety profile in patients with PVD. Patients treated with multiple sequential cycles showed continued reductions in dilator-induced pain and NRS scores with repeated injections, suggesting a potential benefit of repeated aboBoNT-A treatment; trials assessing efficacy and validating DMTS are warranted to explore these findings.

Goldstein, S. W., et al. (2023). "Safety and efficacy of fractional CO2 laser treatment to the vestibule: a randomized, double-blind, sham-controlled, prospective 3-site clinical study in women with vestibular pain." The Journal of Sexual Medicine 20(6): 800-812.
	BACKGROUND: Data are limited regarding fractional CO2 laser as a nonhormonal treatment for vestibular pain. AIM: We sought to perform what is, to our knowledge, the first multisite prospective randomized, double-blind, sham-controlled clinical trial to assess the safety and efficacy of fractional CO2 laser treatment to the vestibule in women with vestibular pain. METHOD(S): Subjects (n=70) meeting inclusion/exclusion criteria at each of 3 sites were randomized 2:1 to active or sham (zero energy) fractional CO2 laser treatment using the vestibular probe (SmartXide2 V2LR - MonaLisa Touch, DEKA, Florence, Italy). Subjects in each treatment arm received 3 treatments 4 weeks apart. At the initial follow-up (week 12), subjects were unblinded and those initially assigned to sham started active treatment. OUTCOME(S): Outcome measures included changes from baseline in sexual activity diaries and scores for the Vulvoscopic Genital Tissue Appearance Scale (VGTA), vestibular cotton-tipped swab testing, McGill Pain Questionnaire, Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and the O'Leary-Sant voiding and pain indices, the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI). RESULT(S): After active treatment, VGTA scores significantly improved in 5 parameters. Pain associated with cotton-tipped swab testing was significantly reduced at weeks 4 through 16 (mean change from baseline -0.64 [95% CI, -0.79 to -0.50] and-1.31 [95% CI, -1.46 to -1.16], respectively). FSFI pain domain scores improved significantly at weeks 12 and 16 (mean change from baseline 0.925 [95% CI, 0.10-1.75] and 1.22 [95% CI, 0.40-2.05], respectively). FSFI total scores increased significantly at weeks 12 and 16 (mean change from baseline 6.24 [95% CI, 2.64-9.85] and 4.96 [95% CI, 1.36-8.57], respectively). FSDS-R scores decreased significantly at weeks 12 and 16 (mean change from baseline -5.84 [95% CI, -8.80 to -2.87] and-9.15 [95% CI, -12.11 to -6.18], respectively). ICSI scores decreased significantly at weeks 12 and 16 (mean change from baseline -0.91 [95% CI, -1.65 to -0.18] and-0.754 [95% CI, -1.49 to -0.02], respectively). ICPI scores decreased significantly at week 16 (mean change from baseline -0.99 [95% CI, -1.63 to -0.34]). In contrast, there were no significant changes in outcomes in the sham arm. No serious adverse events occurred. CLINICAL IMPLICATIONS: Fractional CO2 laser treatment in women with vestibular pain resulted in improvement from baseline in multiple key outcome measures of vestibular health. STRENGTHS AND LIMITATIONS: Strengths of the study were that it was a multisite prospective randomized double-blind, sham-controlled clinical trial that included multiple measures related to vestibular pain and sexual function. Limitations were the nonvalidated primary outcome measure and limited study cohort. CONCLUSION(S): Fractional CO2 laser therapy is a safe and effective nonhormonal treatment for vestibular pain.Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Golfier, F., et al. (2022). "Spontaneous hemoperitoneum in pregnancy: A life-threatening maternal and fetal complication of endometriosis." Journal of Gynecology Obstetrics and Human Reproduction 51(7): 102415.
	Background: Spontaneous hemoperitoneum in pregnancy (SHiP) is a complication of endometriosis. We describe the clinical characteristics and outcomes of mother and fetus in 11 new cases of SHiP with endometriosis and 43 cases reported in the literature since 1995.; Material and Methods: The 60 maternity hospitals in the Auvergne-Rhône-Alpes region in France were contacted to identify cases of SHiP associated with endometriosis. In parallel, a systematic review of the literature used the PRISMA chart to report published cases.; Results: Fifty-four cases of SHIP associated with endometriosis are presented. Twenty-four patients (44%) conceived with assisted reproductive techniques. Hemoperitoneum occurred before delivery in 47/54 cases (87%).The average gestational age of occurrence was 27 weeks (13 weeks to 40+6 weeks). An hypovolemic shock was present in 24/51 (47%) of patients. Forty-six women (85%) were treated by laparotomy, 5 (9%) by laparoscopy, 2 (2%) by interventional radiology. The hemorrhage site was in the mediolateral compartment of the pelvis in 29 cases (54%), corresponding to bleeding from vessels in the broad ligament in 24/29 (83%) of these cases. The mean estimated blood loss was 1957 mL (150-7500 mL). Emergency peripartum hysterectomy was required in 3/54 cases (6%). There were no maternal deaths. The average gestational age at birth was 30 weeks (13+2 weeks to 42 weeks). The fetus died in 19/64 cases (30%).; Conclusion: SHiP is an underestimated potentially fatal complication of endometriosis. Maternal salvage by emergency laparotomy is usually required to identify and treat the bleeding site. Fetal prognosis remains poor.; Competing Interests: Declarations of Competing Interest none. (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Gómez de Quero Córdoba, M., et al. (2021). "[Systematic review of the treatment with pessaries in the pelvic organ prolapse (POP).]." Archivos Espanoles de Urologia 74(3): 306-316.
	Pelvic organ prolapse (POP) has a general incidence of > 10% in the female population of the Western world. The pessary is a silicone device, inserted into the vagina to provide support to the pelvic organs. It is used as a conservative treatment to improve prolapse symptoms.OBJECTIVES: To evaluate the effectiveness of pessary treatment in pelvic organ prolapse through a systematic review of the current literature.MATERIAL AND METHODS: A Scoping Review was carried out based on the PRISMA guidelines for the development of systematic reviews. The PICO research question was asked, the sources of information were selected, and the eligibility criteria were established. Subsequently, the descriptors in health sciences and keywords, combined with Boolean operators, were appliedin each of the search engines. RESULTS: A total of 19 references were included in the analysis of this work. To delimit the data extraction, the information was divided into four dimensions: improvements in symptoms related to POP and quality of life, sexual function; discontinuation, justification for discontinuation and complications. CONCLUSIONS: The pessary produces positive effects on the quality of life of women with POP, with good satisfaction rates. The main reasons for the interruption include: inability to retain the pessary, discomfort, and the desire for surgery.

Gómez de Vicente, J. M. and G. Trelles (2020). "[Laser technology applications in functional urology and urogynecology.]." Archivos Espanoles de Urologia 73(8): 709-723.
	OBJECTIVE: LASER (Light Amplification by Stimulated Emission of Radiation) technology consists of the emission of a high-energy light beam. In medicine, it is used to cut, coagulate, fragment and evaporate biological or synthetic tissues. In the field of Functional Urology and Urogynecology its use has been widely explored. This article tries to give an overview of its applications in this subspecialty. MATERIAL AND METHOD: A non-systematic free search was performed in Pubmed, Embase and Google Scholar,combining the terms "laser", "laser technology", "interstitial cystitis", "trigonitis", "urinary tract infections","mesh", "mesh complications", "microbiome", "menopause genitourinary syndrome", "vulvovaginal atrophy", "urinary incontinence", "pelvic organ prolapse", "lichensclerosus", "complications" and "vaginal laxity". All relevant studies were retrieved in full text, in order to prepare a summary of each of the pathologies in which laser therapy has been used in Functional Urology and Urogynecology over time. RESULTS: There are different types of lasers and different application modalities to treat a wide variety of functional pathologies, including interstitial cystitis, trigonitis, mesh complications, urinary incontinence or pelvic organ prolapse. In some of them its use has been abandoned, despite the fact that, theoretically, they offer advantages over other therapies, such as in the case of interstitial cystitis. In others there is still not enough evidence in terms of safety and efficacy to be an alternativeto other conventional treatments. CONCLUSIONS: Although laser therapy offers certain advantages over other treatments, its use has not been generalized in the subspecialty of Functional Urology and Urogynecology. More evidence is needed to demonstrate its efficacy and safety.

Gómez-Hidalgo Natalia, R., et al. (2022). "Adjuvant therapy in early-stage cervical cancer after radical hysterectomy: are we overtreating our patients? A meta-analysis." Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 24(8): 1605-1614.
	Objective: There is a gap in knowledge regarding the ideal management of patients with early-stage cervical cancer and intermediate-risk features. Here, we present a meta-analysis of the published literature on oncological outcomes in these patients and determine trends in postoperative management.; Methods: MEDLINE and PubMed were used for literature searches. The inclusion criteria were: English language articles including ≥ 10 patients, patients who underwent radical hysterectomy, nodes negative, studies reporting oncological outcomes and complications treatment-related and compare a surgery-only cohort with a radiotherapy cohort. The PRISMA guidelines were followed. Combined relative risk was calculated using DerSimonian-Laird random-effects model and a forest plot was drawn.; Results: We collected 183 manuscripts on early-stage cervical cancer treated with radical hysterectomy alone or with adjuvant radiotherapy after surgery. A total of eight studies met the inclusion criteria. Regarding oncological outcomes, survival was reported in five studies. The relative risk of recurrence and the relative risk of mortality was similar in both groups independently whether receive or not adjuvant therapy. Most of the studies did not report significant differences regarding morbidity treatment related between the groups, except for a higher rate of lymphedema after radiotherapy.; Conclusion: We found that the relative risk of recurrence and mortality was similar in both groups not depending on adjuvant therapy. Therefore, whether radiotherapy adjuvant treatment is indicated remains a topic of debate. (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Gonçalves Caroline, R., et al. (2022). "Hormone therapy in women with premature ovarian insufficiency: a systematic review and meta-analysis." Reproductive Biomedicine Online 44(6): 1143-1157.
	The aim of this systematic review and meta-analysis was to evaluate the effectiveness of different hormone therapies, including hormonal contraceptives, in women with premature ovarian insufficiency (POI). Thirty reports of 28 studies were included, with a total of 4004 participants with POI from diverse aetiologies, of whom 3785 received hormone therapies and 219 received calcium supplementation, vitamin D, placebo or no treatment. Hormone therapy was superior to non-treatment, placebo, calcitriol or calcium in preserving bone mineral density (BMD) in women with POI. Hormone therapy was associated with up to 80% reduction in the prevalence of hot flushes and with stability or improvement in the quality of life scores. Hormone therapy induced significant increases in uterine volume and endometrial thickness in women with POI. The studies yielded convergent results and were of good quality, although some lacked blinding or had incomplete outcome data. Moderate to high quality evidence was found that hormone therapy with oestrogen and progesterone or progestin (including contraceptives) is beneficial to women with POI, not only to mitigate hypoestrogenic symptoms but also to preserve BMD and avoid uterine atrophy. More studies are needed to confirm the long-term safety of this therapy and to assess its possible impact on the risk of hard outcomes such as bone fractures and cardiovascular events. (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Gonçalves-Henriques, M., et al. (2022). "Ulipristal Acetate in Adenomyosis." Gynecology and Minimally Invasive Therapy 11(4): 198-202.
	Adenomyosis is defined as the invasion of the basal endometrium (stroma and glands) into the underlying myometrium. It may lead to abnormal uterine bleeding (AUB), pelvic pain, and infertility. The definitive treatment is hysterectomy. Some conservative measures have been used in patients willing to procreate. Ulipristal acetate is a selective progesterone receptor modulator used to treat AUB caused by leiomyomas. This is a systematic review on the use of ulipristal to treat adenomyosis. Eight eligible articles were retrieved from PubMed, SCOPUS, and Cochrane Library. Only one randomized clinical trial was published until date concerning this matter. It seems that ulipristal acetate induces partial or complete remission of AUB caused by adenomyosis, but the evidence concerning its effect on pelvic pain and the radiologic findings of the disease is conflicting. Nevertheless, given the paucity of data, it is still preliminary to draw any conclusion about the subject.; Competing Interests: There are no conflicts of interest. (Copyright: © 2022 Gynecology and Minimally Invasive Therapy.)

Gong, H., et al. (2020). "Poly (ADP-ribose) polymerase (PARP) inhibitor regimens for ovarian cancer in phase III randomized controlled trials: a network meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 30(10): 1576-1582.
	Introduction: We aimed to evaluate poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) regimens in BRCA-mutated ovarian cancer for patients responsive to front-line platinum (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) or platinum-sensitive relapsed (olaparib, rucaprib, niraparib) patients in phase III randomized controlled trials.; Methods: A network meta-analysis was utilized to generate the direct and indirect comparisons. The primary outcomes for network meta-analysis were efficacy (hazard ratios for progression-free survival in BRCA mutation cohort) and toxicity (odds ratios for all grade 3-4 adverse events). The American Society of Clinical Oncology (ASCO) value framework was used to assess the cost-effectiveness of the PARPi regimens.; Results: Network meta-analysis indicated no statistically significant differences in efficacy and toxicity among the assessed upfront or relapsed PARPi regimens (95% CI included 1). The ASCO value framework indicated that current PARPi regimens were similar in clinical benefits, toxicity, and net health benefit in the upfront (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) and relapsed setting (olaparib, rucaprib, niraparib). The addition of bevacizumab to olaparib ($353.72) increased the cost per unit net health benefit for patients compared with olaparib monotherapy ($260.57). The upfront PARPi regimens had lower toxic scores than the regimens used at relapse.; Conclusions: The choice of PARPi regimens both in the upfront and relapsed setting should consider not only efficacy and toxicity but also costs in BRCA mutation patients. Current combining PARPi regimens are not recommended for such patients in the upfront setting from the cost-effective perspective. Upfront PARPi regimens are less toxic than those used at relapse.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Gong, W., et al. (2023). "Dose-dense regimen versus conventional three-weekly paclitaxel combination with carboplatin chemotherapy in first-line ovarian cancer treatment: a systematic review and meta-analysis." Journal of Ovarian Research 16(1): 136.
	Background: Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer.; Methods: An electronic search following PRISMA guidelines was conducted (Prospero registration number: CRD42020187622), and then a systematic review and meta-analysis of included literature were initiated to determine which regimen was better.; Results: Four randomized controlled trials were included in the qualitative evaluation, and 3699 ovarian cancer patients were included in the meta-analysis. The meta-analysis revealed that the dose-dense regimen could prolong PFS (HR0.88, 95%CI 0.81-0.96; p = 0.002) and OS (HR0.90, 95%CI 0.81-1.02; p = 0.09), but it also increased the overall toxicity (OR = 1.102, 95%CI 0.864-1.405; p = 0.433), especially toxicity of anemia (OR = 1.924, 95%CI 1.548-2.391; p < 0.001), neutropenia (OR = 2.372, 95%CI 1.674-3.361; p < 0.001). Subgroup analysis indicated that the dose-dense regimen could significantly prolong not only PFS (HR0.76, 95%CI 0.63-0.92; p = 0.005 VS HR0.91, 95%CI 0.83-1.00; p = 0.046) but also OS (HR0.75, 95%CI 0.557-0.98; p = 0.037 VS HR0.94, 95%CI 0.83-1.07; p = 0.371) in Asian, and overall toxicity was significantly increased in Asians (OR = 1.28, 95%CI: 0.877-1.858, p = 0.202) compared to non-Asians (OR = 1.02, 95%CI 0.737-1.396, p = 0.929).; Conclusion: Paclitaxel dose-dense regimen could prolong PFS and OS, but it also increased the overall toxicity. Therapeutic benefits and toxicity of dose-dense are more obvious in Asians compared to non-Asians, which need to be further confirmed in clinical trials. (© 2023. The Author(s).)

Gong, Y., et al. (2023). "Effects of carnitine on glucose and lipid metabolic profiles and fertility outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis." Clinical Endocrinology 98(5): 682-691.
	Objectives: To quantify the effect of carnitine on glucose and lipid metabolic profiles and fertility outcomes in women with Polycystic ovary syndrome (PCOS).; Design: A systematic review and meta-analysis were conducted.; Patients: Women with PCOS diagnosed by Rotterdam or Androgen Excess Society (AES) criteria and taking carnitine supplement were assessment.; Measurements: Fertility outcomes (ovulation, clinical pregnancy, live birth, and miscarriage), lipid parameters (BMI, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein), fasting glucose and insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).; Results: In total, 839 participants were included in this analysis. The dosage of carnitine and treatment duration reported by studies varied from 250 mg to 3000 mg daily and 84 to 90 days, respectively. The publication bias was absent. Compared with placebo, carnitine significantly improved ovulation rates (RR 3.42, 95% CI 2.39 to 4.89, I2 = 0%) and pregnancy rates (RR 11.05, 95% CI 1.21 to 100.58, I2 = 79%). None of included studies reported live birth. After treatment, carnitine resulted in significant reductions relative to baseline in body mass index (BMI, MD -0.93 kg/m2, 95% CI -1.15 to -0.70, I2 = 55.0%), insulin levels (MD -2.47 mIU/L, 95% CI -4.49 to -0.45, I2 = 0%) and the Homeostasis Model Assessment index (MD -0.67, 95% CI -1.20 to -0.14, I2 = 0%) than placebo, but not for lipid profiles including triglyceride, total cholesterol, and low-density lipoprotein.; Conclusion: With the available literature, carnitine seems to improve ovulation and clinical pregnancy and insulin resistance, BMI in women with PCOS. These effects are warranted to be further validated, due to insufficient statistical power. (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Gonzales, A. L., et al. (2021). "Prevalence and Treatment of Postpartum Stress Urinary Incontinence: A Systematic Review." Female Pelvic Medicine & Reconstructive Surgery 27(1): e139-e145.
	OBJECTIVES: Many women present for treatment of stress urinary incontinence (SUI) after childbirth. This systematic review describes the efficacy of treatment options for SUI initiated during the 12 months after delivery. METHOD(S): We conducted a systematic review to identify studies comparing treatment options for SUI initiated in the 12 months after parturition. We searched MEDLINE from inception to February 2019, using Medical Subject Heading terms related to pregnancy and urinary incontinence. Preintervention and postintervention populations were compared using analysis of variance with Fisher least significant difference method used to determine efficacy between groups. Grades for Recommendation, Assessment, Development and Evaluation system was used to categorize quality of evidence as high, moderate, low, or very low. RESULT(S): We double screened 4548 abstracts, identifying 98 articles for full-text review. Seven studies met the eligibility criteria and were included. Compared with a control group, the 4 interventions identified outperformed the control group (P < 0.001) using Fisher (with effect sizes noted): (1) supervised pelvic floor physical therapy (0.76), (2) electrical stimulation (0.77), (3) home physical therapy (PT) (0.44), and (4) surgery (not applicable). Based on Grades for Recommendation, Assessment, Development and Evaluation assessment, there was moderate evidence to support PT and electrical stimulation, with insufficient evidence for surgery. There were no significant differences in parity, age, or body mass index via analysis of variance. The overall strength of evidence is poor for the treatment of postpartum SUI; more data are needed to fully evaluate other treatment options. CONCLUSION(S): All identified interventions demonstrated greater improvement for postpartum SUI over no treatment. Supervised PT +/- electrostimulation was the most effective nonsurgical intervention.Copyright © 2020 American Urogynecologic Society. All rights reserved.

Gonzalez, C. D., et al. (2019). "Metformin and pregnancy outcomes: Evidence gaps and unanswered questions." Current Clinical Pharmacology 14(1): 54-60.
	Background: Metformin is sometimes used as an alternative to insulin in gestational diabetes mellitus (GDM). It is also used to achieve ovulation in polycystic ovary syndrome (PCOS). Pre-natal exposure to metformin results from its continuation after a successful ovulation in women with PCOS, its maintenance in women with pre-gestational diabetes or the installation of metformin in GDM. Little is known about the potential consequences of metformin exposure on pregnancy outcomes and offspring development. The aim of this review is to summarize the metformin effects on pregnancy outcomes and offspring development. Gaps in the available evidence and unanswered questions are also discussed. Method(s): A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed, EMBASE and SCIELO databases through 1995 first semester. Result(s): Several factors limit the effect of metformin on embryos. In contrast, placental transport of metformin is effective allowing for a higher fetal exposure; the impact of this finding remains unclear. It seems that the interruption of metformin after a pregnancy diagnosis in women with PCOS is not associated with a higher miscarriage risk and it continuation does not seem to impair the maternal metabolic prognosis or prevent emerging GDM. Conclusion(s): It seems to have no sense to prolong the use of metformin after a pregnancy diagnosis in women with PCOS. Patients with GDM may be treated with metformin under on judicious basis, and a careful attachment to clinical guidelines and regulations is recommended. The long-term effects of pre-natal exposure to metformin on the offspring remain uncertain © 2019 Bentham Science Publishers.

Gonzalez, R. R., et al. (2023). "Three-year patient-reported outcomes of single-incision versus transobturator slings for female stress urinary incontinence are equivalent." International Urogynecology Journal 34(9): 2265-2274.
	Introduction and hypothesis: Patient-reported outcome measures (PROMs) are important for understanding the success of surgery for stress urinary incontinence, as patient perception of success does not always correlate with physician perception of success. We report PROMS after single-incision slings (SIS) and transobturator mid-urethral slings (TMUS). Method(s): This was a planned outcome analysis of secondary endpoints in a study in which the primary aim was to compare efficiency and safety using a non-inferiority design (results reported previously). In this analysis of quality of life (QOL), validated PROMs were collected at baseline, 6, 12, 18, 24, and 36 months to quantify incontinence severity (Incontinence Severity Index), symptom bother (Urogenital Distress Inventory), disease-specific QOL impact (Urinary Impact Questionnaire), and generic QOL impact (PGI-I; not applicable at baseline). PROMs were analyzed within treatment groups as well as between groups. Propensity score methods were used to adjust for baseline differences between groups. Result(s): A total of 281 subjects underwent the study procedure (141 SIS, 140 TMUS). Baseline characteristics were balanced after propensity score stratification. Participants had significant improvement in incontinence severity, disease-specific symptom bother, and QOL impact. Improvements persisted through the study and PROMs were similar between treatment groups in all assessment at 36 months Conclusion(s): Following SIS and TMUS, patients with stress urinary incontinence had significant improvement in PROMs including Urogenital Distress Inventory, Incontinence Severity Index, and Urinary Impact Questionnaire at 36 months, indicating disease-specific QOL improvement. Patients have a more positive impression of change in stress urinary incontinence symptoms at each follow-up visit, indicating generic QOL improvement.Copyright © 2023, The International Urogynecological Association.

Gonzalez-Mena, A., et al. (2024). "Treatment of Women with Primary Dysmenorrhea with Manual Therapy and Electrotherapy Techniques: A Systematic Review and Meta-Analysis." Physical Therapy.
	OBJECTIVE: The objective of this study was to evaluate the efficacy of electrotherapy and manual therapy for the treatment of women with primary dysmenorrhea. METHOD(S): Systematic searches were conducted in Scopus, Web of Science, PubMed, CINAHL, and MEDLINE. The articles must have been published in the last 10 years, had a sample exclusively of women with primary dysmenorrhea, had a randomized controlled trial design, and used interventions that included some form of manual therapy and/or electrotherapy techniques. Two reviewers independently screened articles for eligibility and extracted data. Difference in mean differences and their 95% CIs were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity. RESULT(S): Twelve selected studies evaluated interventions, with 5 evaluating electrotherapy techniques and 7 evaluating manual therapy techniques. All studies analyzed identified improvements in pain intensity and meta-analysis confirmed their strong effect. CONCLUSION(S): Manual therapy and electrotherapy are effective for the treatment of women with primary dysmenorrhea. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage stands out for its effects on the intensity and duration of pain with the application of a few sessions and their long-term effects. IMPACT: Manual therapy techniques and electrotherapy methods reduce the pain intensity of women with primary dysmenorrhea. Quality of life and degree of anxiety improved significantly with manual therapy interventions. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage are the interventions with which positive effects were achieved with fewer sessions.Copyright © The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gonzalo-Encabo, P., et al. (2021). "Dose-response effects of aerobic exercise on adiposity markers in postmenopausal women: pooled analyses from two randomized controlled trials." International journal of obesity (2005) 45(6): 1298‐1309.
	Background/objective: Exercise may reduce the risk of breast cancer through adiposity changes, but the dose‐response effects of exercise volume on adiposity markers are unknown in postmenopausal women. We aimed to compare the dose‐response effects of prescribed aerobic exercise volume on adiposity outcomes. Participants/methods: Data from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were pooled for this analysis (N = 720). These were 12‐month randomized controlled trials, where participants were randomized to 225 min/week (mid‐volume) of aerobic exercise versus usual inactive lifestyle (ALPHA), or 150 min/week (low‐volume) versus 300 min/week (high‐volume) (BETA). Fat mass and fat‐free mass were measured using DXA and intra‐abdominal and subcutaneous fat area were assessed with computed tomography. Results: After 12 months of aerobic exercise, increasing exercise volumes from no exercise/control to 300 min/week resulted in statistically significant reductions in BMI, weight, fat mass, fat percentage, intra‐abdominal and subcutaneous fat area (P < 0.001). Compared with controls, fat mass loss was −1.13, −1.98 and −2.09 kg in the low‐, mid‐ and high‐volume groups, respectively. Similarly, weight loss was −1.47, −1.83, −2.21 kg in the low‐, mid‐ and high‐volume groups, respectively, compared to controls, and intra‐abdominal fat area loss was −7.44, −15.56 and −8.76 cm2 in the low‐, mid‐ and high‐volume groups, respectively, compared to controls. No evidence for a dose‐response effect on fat‐free mass was noted. Conclusion: A dose‐response effect of exercise volume on adiposity markers was noted, however, the differences in adiposity markers were smaller when comparing 225 min/week to 300 min/week of exercise. Given the strong positive associations between obesity and postmenopausal breast cancer risk, this study provides evidence on the importance of exercise volume as part of the exercise prescription to reduce adiposity and, ultimately, postmenopausal breast cancer risk.

Gonzalo-Encabo, P., et al. (2021). "Weight Regain and Breast Cancer-Related Biomarkers Following an Exercise Intervention in Postmenopausal Women." Cancer epidemiology, biomarkers & prevention 30(6): 1260‐1269.
	BACKGROUND: Epidemiologic studies have reported associations between weight fluctuations and postmenopausal breast cancer risk; however, the biological markers involved in this association are unknown. This study aimed to explore the associations between breast cancer‐related biomarkers and weight regain following exercise‐induced weight loss. METHODS: From the 400 participants included in the Breast Cancer and Exercise Trial in Alberta, a total of 214 lost weight during the intervention and had follow‐up blood samples, body composition, and covariate measurements. Outcomes were measured at baseline, 12 months (end of the study), and 24 months (follow‐up). RESULTS: During follow‐up, weight regain was 1.80 kg [95% confidence interval (CI): ‐0.40‐3.90], and was significantly associated with increases in estradiol [treatment effect ratio (TER) = 1.03; 95% CI, 1.01‐1.04], estrone (TER = 1.02; 95% CI, 1.01‐1.03), free estradiol (TER = 1.04; 95% CI, 1.02‐1.05), the homeostatic model assessment for insulin resistance (TER = 1.03; 95% CI, 1.02‐1.05), and insulin (TER = 1.03; 95% CI, 1.01‐1.04), and decreases in sex hormone‐binding globulin (SHBG; TER = 0.98; 95% CI, 0.97‐0.99) levels. Nonstatistically significant associations were found for glucose and C‐reactive protein. Furthermore, a statistically significant linear trend of increasing levels for all biomarkers, and decreasing SHBG, across weight regain categories was found. CONCLUSIONS: These results suggest that weight regain following exercise‐induced weight loss is associated with breast cancer‐related biomarker changes in postmenopausal women. IMPACT: These findings provide evidence to support the importance of developing effective strategies to prevent weight regain and, consequently, decrease postmenopausal breast cancer risk via changes in adiposity‐related biomarkers.

Gopal, S., et al. (2021). "Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study." The Journal of Obstetrics and Gynaecology Research 47(12): 4414-4425.
	BACKGROUND: Perimenopause is the period during which many physiological changes mark the transition into the final menstrual period of a woman and these changes are associated with climacteric symptoms. OBJECTIVES: This study aimed to assess the efficacy and tolerability of an Ashwagandha root extract on the climacteric symptoms, quality of life (QoL), and hormonal parameters in perimenopausal women. MATERIALS AND METHODS: In this 8-week, randomized, double-blind, placebo-controlled study, 100 women with climacteric symptoms were randomly allocated to take either a placebo or 300 mg of an Ashwagandha root extract twice daily. Outcomes were measured using the menopause rating scale (MRS), menopause-specific QoL (MENQoL), hot flash score, and hormonal changes in estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. RESULTS: Among 100 participants enrolled, 91 participants completed the study. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in total MRS score (p < 0.0001), reflected by significant reductions in the psychological (p = 0.0003), somato-vegetative (p = 0.0152), and urogenital (p < 0.0001) domains. Ashwagandha intake demonstrated a statistically significant reduction in total MENQoL scores (p < 0.0001) and was also associated with a statistically significant increase in serum estradiol (p < 0.0001) and a significant reduction in serum FSH (p < 0.0001) and serum LH (p < 0.05) compared with the placebo. There was no significant between the group differences in the serum testosterone level. CONCLUSION: These findings suggest that ashwagandha root extract can be a safe and effective option to relieve mild to moderate climacteric symptoms during perimenopause in women.

Gora, K. B. and S. Wozniak (2023). "Evaluation of effectiveness of pharmacological treatment in pelvic congestion syndrome." Ginekologia polska.
	Pelvic congestion syndrome (PCS) is a pain syndrome characterized by positional pelvic pain and is associated with pelvic and vulvar varicosities as well as symptoms of dyspareunia and postcoital pain. Since the etiology of PCS is complex, the treatment should be individualized. Despite both pharmacological and interventional methods being used, there is significant predominance of minimally invasive therapies e.g. embolization. The study considers the answer to the question of whether pharmacological therapy is altogether effective. Using a combination of keywords, a PubMed search was performed for the years 1987-2022. The relevant articles were appointed and included in this narrative review. Despite the multitude of alternatives for pharmacological treatment, the systemic side effects of the medications used, as well as the interactions between drugs, affect patients' compliance and persistence. Furthermore, the quality of the currently existing evidence, considering the efficacy of the given substances, is low. Because of the adverse effects and thus the limited drug administration period, there is currently insufficient research on long-term effectiveness of the PCS pharmacological treatment. Therefore, prospective, comparative studies with larger patient population sizes are necessary to provide the possibility of efficient pharmacological therapy.

Gorelova, I. V., et al. (2020). "[Vitamin D and reproductive health]." Problemy endokrinologii 66(5): 96-101.
	Vitamin D insufficiency and deficiency in women with infertility is more common than in the population. However, we still do not know the exact mechanisms for the participation of vitamin D in the regulation of reproductive function. The purpose of this study is to analyze actual literature data on the role of vitamin D in the regulation of reproductive system and its influence on using of assisted reproductive technologies for the treatment of infertility. A search was carried out for literary sources published in the NSBI database PubMed, Medline, and others with a search depth of up to 20 years. 135 sources on this topic were studied, of which 54 were included in the analysis. The review presents data obtained in animal studies, in vitro and in clinical studies. Thus, the absence of vitamin D resulted in a dramatical decrease in fertility in both female and male rats and mice, due to the development of hypocalcemia. In vitro studies describe its involvement in the receptive transformation of the endometrium and in the regulation of the immune response during embryo implantation. However, clinical studies often show conflicting results. There is no unequivocal data on the effect of vitamin D levels on spermogram parameters, but a decrease in the pregnancy rate was shown when ovulation was induced in pairs, where a vitamin D deficiency was revealed in men. A meta-analysis published in 2017 showed a decrease in the pregnancy and live birth rate in women with low levels of vitamin D after the use of assisted reproductive technologies (ART). It was not possible to establish whether this decrease depends on oocyte quality or endometrium. There is an opportunity that the effect of vitamin D deficiency on fertility will not come with all forms of infertility. For example, in women with anovulation due to polycystic ovary syndrome, vitamin D deficiency is demonstrated to decrease pregnancy rate in ovulation induction cycles and in ART. Such relationship was not found in women with unexplained infertility.Thus, the role of vitamin D in the pathogenesis of infertility requires further study, as well as the possibilities of therapy in order to increase the effectiveness of infertility treatment methods and assisted reproductive technology programs.

Gori, S., et al. (2024). "Exploring conservative management for cervical intraepithelial neoplasia grade 2 in organised cervical cancer screening programmes: a multicentre study in Italy." Family medicine and community health 12(Suppl 2).
	Cervical intraepithelial neoplasia grade 2 (CIN2) lesions may regress spontaneously, offering an alternative to immediate treatment, especially for women of childbearing age (15-45 years).We conducted a prospective multicentre study on conservative CIN2 management, with semiannual follow-up visits over 24 months, biomarkers' investigation and treatment for progression to CIN3+ or CIN2 persistence for more than 12 months. Here, we assess women's willingness to participate and adherence to the study protocol.The study was set in population-based organised cervical cancer screening.From April 2019 to October 2021, 640 CIN2 cases were diagnosed in women aged 25-64 participating in the screening programmes.According to our predefined inclusion and exclusion criteria, 228 (35.6%) women were not eligible; 93 (22.6%) of the 412 eligible refused, and 319 (77.4%) were enrolled. Refusal for personal reasons (ie, desire to become pregnant, anxiety, difficulty in complying with the study protocol) and external barriers (ie, residence elsewhere and language problems) accounted for 71% and 17%, respectively. Only 9% expressed a preference for treatment. The primary ineligibility factor was the upper age limit of 45 years. After enrolment, 12 (4%) women without evidence of progression requested treatment, 125 (39%) were lost to follow-up (mostly after 6-12 months) and 182 (57%) remained compliant. Remarkably, 40% of enrolees did not fully adhere to the protocol, whereas only 5% (20/412) of the eligible women desired treatment.Our study demonstrates a good acceptance of conservative management for CIN2 lesions by the women, supporting its implementation within cervical screening programmes.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gorman, J. R., et al. (2022). "Opening the Conversation: study protocol for a Phase III trial to evaluate a couple-based intervention to reduce reproductive and sexual distress among young adult breast and gynecologic cancer survivor couples." Trials 23(1): 730.
	Background: Reproductive and sexual health (RSH) concerns are common and distressing for young adults diagnosed with breast and gynecologic cancer and their partners. This study evaluates the efficacy of a virtual couple-based intervention called Opening the Conversation (OC). The OC intervention is grounded in theory and evidence-based practice and was adapted to improve coping and communication specifically in relation to RSH concerns after cancer. Method(s): This Phase III trial is conducted in a fully remote setting and enrolls young adult couples (current age 18-44 years) with a history of breast or gynecologic cancer (stage 1-4, diagnosed under age 40) within the past 6 months to 5 years. Eligible dyads are recruited from across the USA. The target sample size is 100 couples. Dyads are randomly assigned to receive either the 5-session OC intervention or a 4-session active control intervention (Side by Side). The primary outcomes are change in reproductive distress and sexual distress. Secondary outcomes include communication about reproductive concerns, communication about sexual concerns, depressive symptoms, sexual function, relationship quality, relationship intimacy, sexual satisfaction, self-efficacy to communicate about sex and intimacy, and quality of life. An exploratory aim examines whether dyadic coping and communication quality mediate intervention effects on survivors' and partners' reproductive distress or sexual distress. Self-report outcome measures are assessed for both groups at baseline (T1), 2 weeks post-treatment (T2), and 3 months post-treatment (T3). Discussion(s): Despite the importance of RSH for quality of life for young adult cancer survivors and their partners, evidence-based interventions that help couples navigate RSH concerns are lacking. This randomized controlled trial will determine the efficacy of a novel couple-based intervention to reduce distress related to RSH concerns for younger couples after breast or gynecologic cancer, in comparison to an active control intervention. Trial registration: ClinicalTrials.gov NCT04806724. Registered on Mar 19, 2021.Copyright © 2022, The Author(s).

Gouda Mohamed, A. and Z. Thein Kyaw (2023). "Selinexor: Changing the paradigm in patients with TP53 wild-type endometrial cancer?" Med (New York, N.Y.) 4(11): 752-754.
	Recurrent endometrial cancer (EC) remains a therapeutic challenge despite advancements in personalized medicine. SIENDO trial showed the potential clinical benefit of selinexor in patients with TP53 wild-type advanced/recurrent EC. The quest for novel therapeutic avenues and approaches continues as researchers seek a glimmer of hope in an area of uncertainty.; Competing Interests: Declaration of interests K.Z.T. served on the advisory board of Exelixis. M.G. declares no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Goudelocke, C., et al. (2024). "A Multicenter Study Evaluating the FREquency of Use and Efficacy of a Novel Closed-Loop Wearable Tibial Neuromodulation System for Overactive Bladder and Urgency Urinary Incontinence (FREEOAB)." Urology 183: 63-69.
	Objective: To evaluate the effectiveness and safety of a novel wearable neuromodulation system incorporating embedded electromyographic evaluation, representing the first closed-loop wearable therapy for bladder control. Method(s): This 12-week, multicenter, open-label, single-arm study of subjects with overactive bladder assessed response of bladder diary parameters and quality of life (QOL) metrics. Subjects used the transcutaneous tibial neuromodulation system, either once or three times weekly, with evaluations at weeks 1, 4, 8, and 12. Enrolled subjects (N = 96) were assessed for changes in urinary frequency, urgency, and urgency urinary incontinence episodes, and QOL changes using various questionnaires. Result(s): In the intent-to-treat population (N = 96, mean age 60.8 +/- 13.0 years, 88.5% female), significant reductions in 3-day diary parameters were observed for daily voids, incontinence, and urgency episodes at 12 weeks. QOL improvements exceeded the minimal clinically important difference for all QOL questionnaires. Long-term results remained robust at 12 months. Device-related adverse events were mild and there were no device-related serious adverse events. Mean therapy compliance at 12 weeks was 88.5%. High satisfaction rates were reported for the device overall. Conclusion(s): The Avation device demonstrates promising efficacy in treating adults with overactive bladder and urge urinary incontinence. At 12 weeks, both diary parameters and QOL indicators showed significant improvement and remained robust at 12 months. The device had a favorable safety profile with high compliance and patient satisfaction. This novel, closed-loop wearable tibial neuromodulation system represents a significant advancement in bladder control therapy, offering a noninvasive, patient-centered alternative with improved accessibility and ease of use.Copyright © 2023 Elsevier Inc.

Gough, K., et al. (2022). "Differential adherence to peer and nurse components of a supportive care package-The appeal of peer support may be related to women's health and psychological status." Patient Education and Counseling 105(3): 762-768.
	Objective: Knowledge of factors associated with intervention non-adherence may provide insights into the clinical utility of non-pharmacologic interventions. Method(s): This study compared complete and incomplete adherers to two separate components of a novel intervention package for women undergoing curative intent radiotherapy for gynaecological cancer on socio-demographic, clinical and pre-radiotherapy patient-reported outcomes data. Result(s): Adherence to the tailored specialist nurse consultations was satisfactory (71% participated in all available sessions, 19% participated in all but one). Adherence to the telephone peer support sessions was less satisfactory (47% participated in all available sessions, 24% participated in all but one session). Complete adherers to the peer sessions reported significantly lower levels of psychological distress and significantly higher levels of physical, emotional and functional wellbeing before radiotherapy. No other statistically significant differences were observed between complete and incomplete adherers to the nurse- or peer-led sessions. Conclusion(s): Women's ability or motivation to engage with peer support may be influenced by their health and psychological status. Further, the extent of intervention non-adherence to the peer-led component may have compromised the assessment of its efficacy. Practice implications: Peer support may be less acceptable or appropriate for women with more complex care needs. Such women may prefer specialised care from trained professionals.Copyright © 2021

Gould, J. F., et al. (2022). "A Systematic Review of Vitamin D during Pregnancy and Postnatally and Symptoms of Depression in the Antenatal and Postpartum Period from Randomized Controlled Trials and Observational Studies." Nutrients 14(11): 2300.
	Depression is a common mood disorder associated with childbirth and is hypothesized to be affected by low vitamin D. This systematic review identified two randomized controlled trials (RCT) of vitamin D supplementation for the treatment or prevention of depressive symptoms in the perinatal period, as well as 18 observational studies of vitamin D exposure and depression in the antenatal and postnatal periods. Both RCTs claimed an improvement in depressive symptoms in the vitamin D group, although the sample sizes were too small to draw firm conclusions. The case-control and cohort studies had mixed findings and were limited by study quality. There were inconsistent results within the few studies with a more robust methodology or within samples restricted to women likely to have depression. The current evidence is inconclusive due to the poor quality and heterogeneity of studies, likely contributing to the contradictory findings. Given there are already numerous RCTs of prenatal vitamin D supplementation, we recommend adding an appropriate measure of depression in the perinatal period to assist in resolving the uncertainty.Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Goulding Elizabeth, A., et al. (2020). "Low-grade serous ovarian carcinoma: A comprehensive literature review." The Australian & New Zealand Journal of Obstetrics & Gynaecology 60(1): 27-33.
	Background: Low-grade serous ovarian carcinoma (LGSOC) is a unique entity with clinical and molecular characteristics distinct from high-grade serous ovarian carcinoma (HGSOC). To date the majority of research has focused on the more common HGSOC, with treatment recommendations often extrapolated to LGSOC. Women with LGSOC are typically diagnosed younger and have indolent and relatively chemoresistant disease. Recently there have been major research advances in LGSOC.; Aims: This systematic review describes the epidemiological, clinical and molecular characteristics of LGSOC, with advances in research and novel treatment options also discussed.; Materials and Methods: A 10-year comprehensive systematic review of peer-reviewed literature was conducted, with a total of 132 abstracts read, 89 articles reviewed and 49 included in this review.; Results: This review highlights the clinical and molecular features of LGSOC, current and traditional treatment options and areas of current research into targeted agents.; Conclusions: Our growing knowledge about LGSOC as a distinct clinical and molecular entity from HGSOC has led to the investigation of more targeted and tailored therapies as their clinical course, optimal management and therapeutic targets differ. There is a need for ongoing collaborative research to provide better treatment options for these patients. (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Govahi, A., et al. (2023). "Antitumor Effects of Curcumin on Cervical Cancer with the Focus on Molecular Mechanisms: An Exegesis." Current Pharmaceutical Design 29(42): 3385-3399.
	Cervical cancer is one of the most prevalent malignancies among females and is correlated with a significant fatality rate. Chemotherapy is the most common treatment for cervical cancer; however, it has a low success rate due to significant side effects and the incidence of chemo-resistance. Curcumin, a polyphenolic natural compound derived from turmeric, acts as an antioxidant by diffusing across cell membranes into the endoplasmic reticulum, mitochondria, and nucleus, where it performs its effects. As a result, it's been promoted as a chemo-preventive, anti-metastatic, and anti-angiogenic agent. As a consequence, the main goal of the present review was to gather research information that looked at the link between curcumin and its derivatives against cervical cancer. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Govindarajah, N., et al. (2019). "Sphingolipids and acid ceramidase as therapeutic targets in cancer therapy." Critical Reviews in Oncology/Hematology 138: 104-111.
	Background: Sphingolipids have been shown to play a key part in cancer cell growth and death and have increasingly become the subject of novel anti-cancer therapies. Acid ceramidase, a sphingolipid enzyme, has an important role in the regulation of apoptosis. In this review we aim to assess the current evidence supporting the role of sphingolipids in cancer and the potential role that acid ceramidase may play in cancer treatment. Method(s): A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string "acid ceramidase", "sphingolipid", "cancer". Additional papers were detected by scanning the references of relevant papers. A summary of the evidence for each cancer subgroup was then formed. Given the nature of the data extracted, no meta-analysis was performed. Result(s): Over expression of acid ceramidase has been demonstrated in a number of human cancers. In vitro data demonstrate that manipulation of acid ceramidase may present a useful therapeutic target. In the clinical setting, a number of drugs have been investigated with the ability to target acid ceramidase, with the most promising of those being small molecular inhibitors, such as LCL521. Conclusion(s): The role of the sphingolipid pathway in cancer is becoming very clearly established by promoting ceramide accumulation in response to cancer or cellular stress. Acid ceramidase is over expressed in a variety of cancers and has a role as a potential target for inhibition by novel specific inhibitors or off-target effects of traditional anti-cancer agents. Further work is required to develop acid ceramidase inhibitors safe for progression to clinical trials.Copyright © 2019

Goyal, M., et al. (2021). "Cesarean myomectomy in the last ten years; A true shift from contraindication to indication: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 256: 145-157.
	Background: A lot of debate is present about Cesarean myomectomy (CM) in women with uterine myoma whether to consider it a feasible and safe procedure or an absolute contraindication.; Objective: To assess the safety and feasibility of myomectomy during cesarean section in women with uterine myoma.; Search Strategy: Electronic search was made on MEDLINE, EMBASE, Cochrane Library, ISI web of knowledge and Scopus from January 1, 2008 to December 31, 2019 using terms "Caesarean section", "Myomectomy", "Fibroid", "Caesarean myomectomy".; Selection Criteria: All full length studies either prospective or retrospective that address caesarean myomectomy were included.; Data Collection and Analysis: The outcomes studied were haemorrhage, mean change in haemoglobin, operative time, need for blood transfusion, febrile morbidity and duration of hospital stay.; Results: Total 249 studies were assessed for eligibility and 17 studies included in analysis with 6545 women. There were 4702 (71.85 %) women in caesarean myomectomy (CM) group and 1843 (28.15 %) women in cesarean section (CS) group. There was statistically significant but clinically insignificant decrease in hemoglobin [MD = 0.27, 95 %CI = 0.08-0.45, p = 0.005; very low quality], significant higher need for blood transfusion [RR = 1.45, 95 %CI = 1.05-1.99, p = 0.02; high quality] in CM group versus CS alone. The mean operative time (minutes) [MD = 14.77, 95 %CI = 6.91-22.64, p = 0.0002; moderate quality] and mean hospital stay (days) [MD = 0.36, 95 %CI = 0.19-0.53, p < 0.00001; high quality] was significantly less in CM group, though of not any clinical significance. No difference in incidence of haemorrhage [RR = 1.16, 95 %CI = 0.86-1.56, p = 0.32; moderate quality evidence] and fever [RR = 1.17, 95 %CI = 0.83-1.65), p = 0.36; moderate quality] in two groups.; Conclusions: The meta-analysis suggests CM is associated with clinical insignificant increase in operative time, blood loss and hospital stay, especially with multiple and large size myomas. CM should be preferred over CS alone especially by experienced surgeons with appropriate haemostatic techniques and tertiary care centres.; Competing Interests: Declaration of Competing Interest The authors report no declarations of interest. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Gozlersuzer, O., et al. (2023). "Investigation of the effectiveness of magnetic field therapy in women with urinary incontinence: Literature review." Urologia Journal 90(1): 51-57.
	Objective: Magnetic stimulation (MS) provides a novel strategy for the treatment of urinary incontinence (UI), although its efficacy remains uncertain. This systematic review both evaluated the effects of MS treatment on UI and investigated its impacts on female patients' life quality. Method(s): A review of the literature that was conducted in EMBASE, PubMed, Google Scholar, and the Cochrane Library (2016-2021) with the search terms; Incontinence of stress OR urge of urination OR Urinary incontinence mixed type. The search was carried out for all randomised controlled trials (RCTs) in English. A manual search has also been conducted for the reference lists of the studies found. Seven studies, with a total of 523 patients (475 patients with SUI), 12 urge urinary incontinence. The study included patients with (UUI) and 36 patients with mixed urinary incontinence (MUI). A total of 10 male patients were excluded from the study. In the included studies, The International Incontinence Questionnaire-Short Form was used to investigate the effects of MS therapy on UI symptoms (ICIQ-SF). Result(s): According to the literature review, MS is an effective therapy option for female patients with UI. Still, to establish the efficacy of MS in this area, more large-scale, high-quality RCTs with extended follow-up periods that use consistent stimulation modalities and evaluate comparable outcomes are needed. Conclusion(s): MS treatment leads to an improvement in the symptoms of UI, in addition to an associated Improved quality of life for patients, without any reported side effects, while the longer-term treatment outcomes must be determined by long-term trials.Copyright © The Author(s) 2022.

Grabowski, J. P., et al. (2022). "PERCEPTION: Phase II investigational study of pembrolizumab combination with chemotherapy in platinum-sensitive recurrent low-grade serous ovarian cancer- A NOGGO trial." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Low-grade serous ovarian cancer (LGSOC) represents a minority within the group of invasive epithelial ovarian malignancies. Recent analyses showed a very limited responsiveness to chemotherapy in LGSOC. Since bevacizumab many years ago, none other agents have been approved in LGSOC. There is a high demand of new therapy combinations with modern substances to improve the response rate and prognosis in this group of patients. Immune check-point inhibitors provide a new possibility which showed to be effective in different malignant diseases as well as in selected ovarian cancer patients. In this study, the standard chemotherapy is going to be combined with pembrolizumab in recurrent LGSOC cases with therapy free interval (TFI) over 6 months after last platinum-based chemotherapy. To the authors knowledge no comparable studies have been performed or planned. If our trial should show pembrolizumab effectivity in LGSOC, it would be a signal and impulse for future clinical studies in this rare disease. Method(s): PERCEPTION/NOGGO-ov44 (NCT04575961) clinical trial is a multi-center, single-arm phase 2 study to evaluate pembrolizumab therapy concomitant to platinum-based chemotherapy (carboplatin plus pegylated liposomal doxorubicin, carboplatin plus gemcitabine or carboplatin monotherapy) and as maintenance in recurrent low-grade serous ovarian cancer cases. LGSOC patients with progression or recurrence at least six months after most previous platinum-containing therapy and in good general performance (ECOG 0 or 1) are eligible to participate in this clinical trial. The primary objective is the 12 months progression free survival (PFS) rate. Secondary end-points include overall survival, response rate (RR), PFS and RR according to Ki67 expression levels, time to first subsequent therapy (TFST) and its response, safety and quality of life. The trial is planned according to Simon's two-stage design with total sample size up to 33 patients. The null hypothesis is PFS-rate after 12 months of 20%. In the first phase 18 patients will be enrolled and if at least 5 patients show PFS after 12 months the study is going to be continued with an additional 15 patients. The trial is claimed successful, if at least 11 patients show PFS after 12 months. Assuming a true PFS-rate of 40%, this trial has 5% type I error rate and 80% power.

Grace, L., et al. (2022). "Fezolinetant for Moderate to Severe Vasomotor Symptoms Associated with Menopause: Effectiveness and Value."
	
Grace, L., et al. (2023). Ketamine Tolerated Dose for Postpartum Depression and Pain After Cesarean Delivery.
	No Results Available Drug: Ketamine (Ketalar) Dose Level 1|Drug: Ketamine (Ketalar) Dose Level 2|Drug: Ketamine (Ketalar) Dose Level 3|Drug: Ketamine (Ketalar) Dose Level 4 Maximum Tolerated Dose of ketamine|Patient reported acceptability of any reported side effects Female Phase 1 12 Other|NIH Allocation: N/A|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Other STUDY22100018|1R01MH134538-01 July 2026

Gracia, M. and Q. Isern (2023). "Controversy in the treatment of uterine fibroids." Clinica e Investigacion en Ginecologia y Obstetricia 50(3): 100854.
	Uterine fibroids are the most common tumours in women of reproductive age, but only 25% of women will require treatment due to the presence of symptoms. There are few randomised studies that have compared the different treatment options for uterine myoma; for the moment, surgery remains the option that offers the best rates of symptomatic resolution, improved quality of life, and a lower recurrence rate. Despite the widespread use of myoma surgery, it seems reasonable to believe that by reducing surgical treatments, either with less invasive therapies or with new medical treatments, both associated morbidity and costs would be reduced. In this sense, ablative techniques for myoma treatment, UAE, HIFU, and radiofrequency, have demonstrated results in terms of symptomatic control and quality of life comparable to surgery, with a low rate of major complications. Recurrence rates and the impact on patients' future fertility would be the main concern. Future long-term comparative studies of ablative techniques and surgical approaches are needed.Copyright © 2023

Graham, R. and C. Kotsopoulos Ioannis (2023). "A comparison of end-to-end and end-to-side anastomosis following rectosigmoid resection in ovarian cancer cytoreductive surgery." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49(2): 468-474.
	Introduction: A rectosigmoid resection with anastomosis is a common component of cytoreductive surgery for ovarian cancer. Evidence from colorectal studies suggests that end-to-side anastomoses may be associated with fewer complications than end-to-end approaches, but these have not previously been compared in an ovarian cancer patient cohort.; Materials and Methods: Over a 51-month period, 239 patients underwent cytoreductive surgery for FIGO stage III/IV ovarian cancer. A rectosigmoid resection was performed in 79 (33.1%) with anastomosis in 59 (74.7%). Pre-operative and intra-operative factors associated with anastomotic leak, and post-operative complications were compared by anastomotic technique.; Results: Anastomoses were end-to-end in 33 (55.9%) and end-to-side in 26 (44.1%) patients. There was a greater proportion of patients with a higher American Society of Anaesthesiologists score in the end-to-side group, but no other statistically significant differences in pre-or intra-operative factors between the groups. There were three (9.1%) cases of anastomotic leak in the end-to-end group, and no leaks in the end-to-side group, but the difference did not reach statistical significance. Both leaks were small, and successfully conservatively managed. There was no significant difference in rate of Clavien Dindo grade III/IV complications, although there was a higher rate of grade II complications following an end-to-side anastomosis (p = 0.036). There was no difference in length of stay, time to restarting chemotherapy, re-operation or 90-day mortality rate.; Conclusion: There was no significant difference in major morbidity following end-to-end or end-to-side anastomosis. Prospective randomised trials specifically focussed in ovarian cancer are needed.; Competing Interests: Declaration of competing interest None. (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Graham, S., et al. (2022). "Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(11): 891-910.
	Objective: The objective of the present document was to review/summarize reported outcomes compared between menopausal hormone therapy (MHT) containing estradiol (E2) versus other estrogens and MHT with progesterone (P4) versus progestins (defined as synthetic progestogens). Methods: PubMed and EMBASE were systematically searched through February 2021 for studies comparing oral E2 versus oral conjugated equine estrogens (CEE) or P4 versus progestins for endometrial outcomes, venous thromboembolism (VTE), cardiovascular outcomes, breast outcomes, cognition, and bone outcomes in postmenopausal women. Results: A total of 74 comparative publications were identified/summarized. Randomized studies suggested that P4 and progestins are likely equally effective in preventing endometrial hyperplasia/cancer when used at adequate doses. E2- versus CEE-based MHT had a similar or possibly better risk profile for VTE and cardiovascular outcomes, and P4- versus progestin-based MHT had a similar or possibly better profile for breast cancer and cardiovascular outcomes. E2 may potentially protect better against age-related cognitive decline and bone fractures versus CEE; P4 was similar or possibly better versus progestins for these outcomes. Limitations are that many studies were observational and some were not adequately powered for the reported outcomes. Conclusions: Evidence suggests a differential effect of MHT containing E2 or P4 and those containing CEE or progestins, with some evidence trending to a potentially better safety profile with E2 and/or P4.

Grammatis Alexandros, L., et al. (2021). "Pentoxifylline for the treatment of endometriosis-associated pain and infertility." The Cochrane Database of Systematic Reviews 8: CD007677.
	Background: Endometriosis is a chronic inflammatory condition that occurs during the reproductive years. It is characterised by endometrium-like tissue developing outside the uterine cavity. This endometriotic tissue development is dependent on oestrogen produced primarily by the ovaries and partially by the endometriotic tissue itself, therefore traditional management has focused on ovarian suppression. In this review we considered the role of modulation of the immune system as an alternative approach. This is an update of a Cochrane Review previously published in 2012.; Objectives: To determine the effectiveness and safety of pentoxifylline in the management of endometriosis. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, and AMED on 16 December 2020, together with reference checking and contact with study authors and experts in the field to identify additional studies.; Selection Criteria: We included randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no treatment, other medical treatment, or surgery in women with endometriosis. The primary outcomes were live birth rate and overall pain (as measured by a visual analogue scale (VAS) of pain, other validated scales, or dichotomous outcomes) per woman randomised. Secondary outcomes included clinical pregnancy rate, miscarriage rate, rate of recurrence, and adverse events resulting from the pentoxifylline intervention.; Data Collection and Analysis: Two review authors independently assessed studies against the inclusion criteria, extracted data, and assessed risk of bias, consulting a third review author where required. We contacted study authors as needed. We analysed dichotomous outcomes using Mantel-Haenszel risk ratios (RRs), 95% confidence intervals (CIs), and a fixed-effect model. For small numbers of events, we used a Peto odds ratio (OR) with 95% CI instead. We analysed continuous outcomes using the mean difference (MD) between groups presented with 95% CIs. We used the I 2 statistic to evaluate heterogeneity amongst studies. We employed the GRADE approach to assess the quality of the evidence.; Main Results: We included five parallel-design RCTs involving a total of 415 women. We included one additional RCT in this update. Three studies did not specify details relating to allocation concealment, and two studies were not blinded. There were also considerable loss to follow-up, with four studies not conducting intention-to-treat analysis. We judged the quality of the evidence as very low. Pentoxifylline versus placebo No trials reported on our primary outcomes of live birth rate and overall pain. We are uncertain as to whether pentoxifylline treatment affects clinical pregnancy rate when compared to placebo (RR 1.38, 95% CI 0.91 to 2.10; 3 RCTs, n = 285; I 2 = 0%; very low-quality evidence). The evidence suggests that if the clinical pregnancy rate with placebo is estimated to be 20%, then the rate with pentoxifylline is estimated as between 18% and 43%. We are also uncertain as to whether pentoxifylline affects the recurrence rate of endometriosis (RR 0.84, 95% CI 0.30 to 2.36; 1 RCT, n = 121; very low-quality evidence) or miscarriage rate (Peto OR 1.99, 95% CI 0.20 to 19.37; 2 RCTs, n = 164; I 2 = 0%; very low-quality evidence). No trials reported on the effect of pentoxifylline on improvement of endometriosis-related symptoms other than pain or adverse events. Pentoxifylline versus no treatment No trials reported on live birth rate. We are uncertain as to whether pentoxifylline treatment affects overall pain when compared to no treatment at one month (MD -0.36, 95% CI -2.12 to 1.40; 1 RCT, n = 34; very low-quality evidence), two months (MD -1.25, 95% CI -2.67 to 0.17; 1 RCT, n = 34; very low-quality evidence), or three months (MD -1.60, 95% CI -3.32 to 0.12; 1 RCT, n = 34; very low-quality evidence). No trials reported on adverse events caused by pentoxifylline or any of our other secondary outcomes. Pentoxifylline versus other medical hera ies One study (n = 83) compared pentoxifylline to the combined oral contraceptive pill after laparoscopic surgery to treat endometriosis, but could not be included in the meta-analysis as it was unclear if the data were presented as +/- standard deviation and what the duration of treatment was. No trials reported on adverse events caused by pentoxifylline or any of our other secondary outcomes. Pentoxifylline versus conservative surgical treatment No study reported on this comparison.; Authors' Conclusions: No studies reported on our primary outcome of live birth rate. Due to the very limited evidence, we are uncertain of the effects of pentoxifylline on clinical pregnancy rate, miscarriage rate, or overall pain. There is currently insufficient evidence to support the use of pentoxifylline in the management of women with endometriosis with respect to subfertility and pain relief outcomes. (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Grandi, G., et al. (2019). "Hormonal contraception in women with endometriosis: a systematic review." The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception 24(1): 61-70.
	Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence.; Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment.; Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence.; Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.

Grandone, E., et al. (2024). "Concerns about the ALIFE2 trial." The Lancet 403(10423): 246.
	
Granell José, C., et al. (2023). The Effectiveness of Transvaginal Radiofrequency in Women With Stress Urinary Incontinence.
	The present study is a double-blind randomized clinical trial. Two groups are located, case group and placebo group. The total number of sessions will be 18 sessions per patient, divided into three sessions per week for a total of six weeks. These sessions last one hour, with a net treatment time of 40 minutes in the supine position. The vaginal probe is inserted into the cavity using a lubricant suitable for intracavitary use and RF, the device is turned on, while the RF is applied, pelvic floor contractions are performed guided by the physiotherapist 2 (Marta Martínez Colmenar) . The evaluations before and after the study will be carried out by the physiotherapist 1 (Yasmin Er Rabiai Boudallaa) who is blinded to group allocation. All participants will be assessed before, after six weeks and 6 months after the start of the study.

Grant Christopher, R., et al. (2023). "Endometrial Adenocarcinoma with Discordant Microsatellite Stability Status Treated with First-Line Pembrolizumab: A Case Report and Narrative Review." The American journal of case reports 24: e939448.
	BACKGROUND Microsatellite instability (MSI) is a hallmark of specific cancers and can be diagnosed using both tissue- and liquid-based approaches. When these tissue- and liquid-based approaches give differing results, they are known as discordant or being at variance. MSI-H tumors are well-researched candidates for treatment with programmed cell death protein 1 (PD-1) inhibitor-based immunotherapy, but the efficacy of immunotherapy in MSI-H discordant endometrial cancer, especially as first-line therapy, is not yet well documented in the literature. CASE REPORT A 67-year-old woman presented with a retroperitoneal mass positive for recurrent adenocarcinoma of endometrial origin. Her stage I endometrial adenocarcinoma 7 years ago demonstrated microsatellite stable (MSS) by immunohistochemical (IHC) stain and indeterminant due to insufficient tissue by Caris Next-Generation Sequencing (NGS). She then presented with a retroperitoneal mass that was MSI-H on IHC stain and Caris NGS, as well as MSI high on liquid biopsy @Guardant360 (@G360). The patient proceeded with pembrolizumab treatment 1 year ago and has sustained a complete clinical response at the time of writing. CONCLUSIONS Our case provides further evidence for the need to retest the microsatellite stability of metastatic sites, especially after a long disease-free survival. Here, we providing a literature review of case reports and a review of studies outlining discordance of testing modalities. Our case also highlights the importance of considering the use of immunotherapy as a first-line agent in patients who may have a poor ECOG performance status, as it can significantly improve their quality of life and reduce the number of adverse effects compared to chemotherapy.

Grant, W. B. (2019). "Vitamin D and health in the Mediterranean countries." Hormones 18(1): 23-35.
	Vitamin D, traditionally well known for its role in maintaining optimal health through its contribution to calcium metabolism and skeletal health, has received increased attention over the past two decades, with considerable focus being placed on its nonskeletal benefits. This paper is a narrative review of the nonskeletal health benefits of vitamin D, of particular interest to inhabitants of Mediterranean countries, namely, autism, cancer, cardiovascular disease, chronic obstructive pulmonary disease, dental caries, diabetes mellitus, erectile dysfunction, hypertension, metabolic syndrome, respiratory tract infections, all-cause mortality, and pregnancy and birth outcomes, because of the relatively high incidence and/or prevalence of these disorders in this region. Currently, the best evidence is coming out of observational studies related to serum 25-hydroxyvitamin D [25(OH)D] concentrations. Vitamin D clinical trials have generally been poorly designed and conducted, usually being based on vitamin D dose rather than 25(OH)D concentration. The optimal 25(OH)D concentration is above 75 nmol/l (30 ng/ml), with even better health outcomes in the range of 100-150 nmol/l. Achieving these concentrations with vitamin D3 supplements will require 1000-4000 IU/day of vitamin D3. Sensible sun exposure should also be encouraged. Countries should also consider fortifying grain and dairy products with vitamin D3.Copyright © 2018, Hellenic Endocrine Society.

Grau, J.-F., et al. (2023). "Advances in immunotherapy in cervical cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(3): 403-413.
	Cervical cancer represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches have a dismal prognosis. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab. However, the introduction of immune checkpoint inhibitors has revolutionized the treatment of this disease, achieving historical overall survival improvements in both the post-platinum and front-line settings. Interestingly, the clinical development of immunotherapy in cervical cancer is currently advancing to the locally advanced setting, although preliminary efficacy outcomes in this setting have been disappointing so far. Moreover, promising data are emerging from early-phase trials on novel immunotherapy approaches, such as human papillomavirus therapeutic vaccines and adoptive cell therapy. This review summarizes the main clinical trials carried out in the field of immunotherapy in the last several years.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Gray, L., et al. (2023). "Does resistance training ameliorate cancer-related fatigue in cancer survivors? A systematic review with meta-analysis." Disability and Rehabilitation: 1-10.
	Purpose: Cancer-related fatigue (CRF) is unrelenting. As neither rest nor sleep ameliorates cognitive, emotional, and physical symptoms, quality of life is diminished. This study examines resistance training (RT) effectiveness on CRF in cancer survivors. The secondary aims were to identify the dose-response relationship of RT frequency, intensity, and volume on CRF in different cancer survivor populations.; Materials and Methods: Systematic searches via numerous databases for RCTs were performed in June 2022. Patient-reported outcome measures (PROM), were analysed, pre-to-post intervention, using a random-effects model. The Physiotherapy Evidence Database (PEDro) scale informed methodological quality assessment.; Results: Eight studies were included (cancer survivors: breast (BCS) = 5; endometrial (ECS) = 1; prostate (PCS) = 2). Overall, RT interventions ≥ 6 weeks elicited large significant reductions in CRF for FACIT-F (SMD = 0.932, p = <0.001) and moderate significant reductions in CRF for PFS-R (SMD = -0.622, p = 0.004).; Conclusion: Main findings indicate that RT ameliorates CRF, especially in BCS; however, individualised approaches should be advocated. Supervised training elicited the greatest positive outcomes, thus should be a pivotal part of the cancer rehabilitation pathway. Future studies should be adequately powered, undertake discrete analyses of different cancer types, and investigate chronic RT effects.

Graz Medical University, o. (2022). Acupuncture in a Multidisciplinary Approach for Vulvodynia and Chronic Pelvic Pain.
	No Results Available Procedure: Acupuncture Change of Subjective Pain Perception|Change of Health-related quality of life - DSF|Change of Health-related quality of life - PHQ-D|Change of Health-related quality of life - PSQ|Change of Health-related quality of life - EHP-30|Change of Subjective improvement|Patient treatment satisfaction Female Not Applicable 68 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Amalia V2.4. July 2025

Green Daniel, S., et al. (2023). "Intraperitoneal Monocytes plus IFNs as a Novel Cellular Immunotherapy for Ovarian Cancer: Mechanistic Characterization and Results from a Phase I Clinical Trial." Clinical cancer research : an official journal of the American Association for Cancer Research 29(2): 349-363.
	Purpose: Ovarian cancer is the most lethal gynecologic cancer and intrinsically resistant to checkpoint immunotherapies. We sought to augment innate immunity, building on previous work with IFNs and monocytes.; Patients and Methods: Preclinical experiments were designed to define the mechanisms of cancer cell death mediated by the combination of IFNs α and γ with monocytes. We translated these preclinical findings into a phase I trial of autologous IFN-activated monocytes administered intraperitoneally to platinum-resistant or -refractory ovarian cancer patients.; Results: IFN-treated monocytes induced caspase 8-dependent apoptosis by the proapoptotic TRAIL and mediated by the death receptors 4 and 5 (DR4 and DR5, respectively) on cancer cells. Therapy was well tolerated with evidence of clinical activity, as 2 of 9 evaluable patients had a partial response by RECIST criteria, and 1 additional patient had a CA-125 response. Upregulation of monocyte-produced TRAIL and cytokines was confirmed in peripheral blood. Long-term responders had alterations in innate and adaptive immune compartments.; Conclusions: Given the mechanism of cancer cell death, and the acceptable tolerability of the clinical regimen, this platform presents a possibility for future combination therapies to augment anticancer immunity. See related commentary by Chow and Dorigo, p. 299. (©2022 American Association for Cancer Research.)

Green, S. M., et al. (2024). "Cognitive Behavioural Therapy for Sexual Concerns During Peri- and Post-Menopause: Preliminary Outcomes." Journal of Neurosurgical Anesthesiology 36(1): 1265.
	Objective: Sexual concerns are reported by 68% to 86.5% of peri- and post-menopausal women, which negatively impact physical and emotional well-being. Despite this, little attention has been paid to this area in the literature and no well-established, nonpharmacological treatments exist. The primary objective of this study is to evaluate the efficacy of a four-session individual Cognitive Behavioural Therapy protocol in improving sexual satisfaction and reducing distress during peri- and post-menopause (CBT-SC-Meno). Secondary objectives include sexual functioning, relationship satisfaction, body image, menopausal symptoms, depression, and anxiety. Design(s): Participants (n=20) recruited during peri- or post-menopause experiencing primary sexual concerns were assessed for study eligibility during an initial assessment. Eligible participants (n=15) were assigned to a waitlist control condition for four weeks, after which they completed four individual CBT sessions focusing on sexual concerns. Participants completed measures assessing sexual satisfaction, distress, and desire [Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Female Sexual Desire Questionnaire (FSDQ)], as well as menopause symptoms [Greene Climacteric Scale (GCS)], body image [Dresden Body Image Questionnaire (DBIQ)], relationship satisfaction [Couples Satisfaction Index (CSI)], depression [Beck Depression Inventory-II (BDI-II)], and anxiety [Hamilton Anxiety Rating Scale (HAM-A)] at baseline, post-waitlist, and post-treatment. Participants also completed the Client Satisfaction Questionnaire at post-treatment. Result(s): No significant changes were observed during the waitlist period across all measures, apart from the FSDQ concern subscale. Participants experienced a significant decrease in symptoms of sexual distress, concern, and resistance, menopausal symptoms, and symptoms of depression. Significant increases in sexual dyadic desire, sexual functioning, body-image satisfaction, and relationship satisfaction were also observed. No significant changes were observed in anxiety symptoms, although post-waitlist scores were indicative of mild anxiety. Further, 100% of participants indicated that they were very satisfied with the treatment and that it helped them cope with their symptoms more effectively. Qualitative treatment satisfaction outcomes were captured and will be reported at the time of presentation. Conclusion(s): To our knowledge, this study is the first to examine the efficacy of a CBT protocol aimed at improving sexual concerns experienced during peri- and post-menopause. Preliminary results suggest CBT-SC-Meno leads to significant improvements across sexual concern domains, as well as commonly co-occurring symptoms including bodyimage, relationship satisfaction, menopausal and depression symptoms. As consumer demand increases for non-pharmacological treatments for peri- and post-menopause symptoms, this form of treatment may not only be preferred by some, but necessary for others as medications, including long-term hormonal-based treatments, have known associated adverse risks. (Figure Presented).

Greer, A., et al. (2021). "Impact of residual disease at interval debulking surgery on platinum resistance and patterns of recurrence for advanced-stage ovarian cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(10): 1341-1347.
	OBJECTIVE: To evaluate the impact of size and distribution of residual disease after interval debulking surgery on the timing and patterns of recurrence for patients with advanced-stage epithelial ovarian cancer. METHODS: Patient demographics and data on disease treatment/recurrence were collected from medical records of patients with stage IIIC/IV epithelial ovarian cancer who were managed with neoadjuvant chemotherapy/interval debulking surgery between January 2010 and December 2014. Among patients without complete surgical resection but with ≤1 cm of residual disease, the number of anatomic sites (<1 cm single anatomic location vs <1 cm multiple anatomic locations) was used to describe the size and distribution of residual disease. RESULTS: A total of 224 patients were included. Of these, 70.5% (n=158) had a complete surgical resection, 12.5% (n=28) had <1 cm single anatomic location, and 17.0% (n=38) had <1 cm multiple anatomic locations. Two-year progression-free survival for complete surgical resection, <1 cm single anatomic location, and <1 cm multiple anatomic locations was 22.2%, 17.9% and 7%, respectively (p=0.007). Size and distribution of residual disease after interval debulking surgery did not affect location of recurrence and most patients had recurrence at multiple sites (complete surgical resection: 64.7%, <1 cm single anatomic location: 55.6%, and <1 cm multiple anatomic locations: 71.4%). Controlling for additional factors that may influence platinum resistance and surgical complexity, the rate of platinum-resistant recurrence was similar for patients with complete surgical resection and <1 cm single anatomic location (OR=1.07, 95% CI 0.40 to 2.86; p=0.888), but women with <1 cm multiple anatomic locations had an increased risk of platinum resistance (OR=3.09, 95% CI 1.41 to 6.78 p=0.005). CONCLUSIONS: Despite current classification as 'optimal,' <1 cm multiple anatomic location at the time of interval debulking surgery is associated with a shorter progression-free survival and increased risk of platinum resistance.

Greff, D., et al. (2023). "Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials." Reproductive biology and endocrinology : RB&E 21(1): 10.
	Background: Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.; Objective: Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.; Methods: The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).; Results: Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).; Conclusion: Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.; Trial Registration: PROSPERO registration number: CRD42021283275. (© 2023. The Author(s).)

Greg, M., et al. (2021). "Effect of Single and Double Layer Cesarean Section Closure on Residual Myometrial Thickness and Isthmocele - a Systematic Review and Meta Analysis."
	
Greg, M., et al. (2021). "Systematic Review and Meta Analysis of the Effect of Gabapentin on Female Chronic Pelvic Pain in Placebo Controlled Randomized Controlled Trials." PROSPERO International prospective register of systematic reviews.
	
Greg, M., et al. (2021). "Effect of 20% Intravenous Fat Emulsion Therapy on Pregnancy Outcomes in Women with RPL or RIF undergoing IVF/ICSI: A Systematic Review and Meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Gregory Stephanie, N., et al. (2023). "Oregovomab Plus Chemo in Newly Diagnosed Patients with Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery (FLORA-5/GOG-3035)." Annals of Surgical Oncology 30(3): 1299-1301.
	
Greig, J., et al. (2023). "Sacral neuromodulation in the management of chronic pelvic pain: A systematic review and meta-analysis." Neurourology and Urodynamics 42(4): 822-836.
	Introduction: Sacral neuromodulation (SNM) is a treatment approved for use in several conditions including refractory overactive bladder (OAB) and voiding dysfunction. Chronic pelvic pain (CPP) is a debilitating condition for which treatment is often challenging. SNM shows promising effect in patients with refractory CPP. However, there is a lack of clear evidence, especially in long-term outcomes. This systematic review will assess outcomes of SNM for treating CPP. Method(s): A systematic search of MEDLINE, Embase, Cochrane Central and clinical trial databases was completed from database inception until January 14, 2022. Studies using original data investigating SNM in an adult population with CPP which recorded pre and posttreatment pain scores were selected. Primary outcome was numerical change in pain score. Secondary outcomes were quality of life assessment and change in medication use and all-time complications of SNM. Risk of bias was assessed using the Newcastle Ottawa Tool for cohort studies. Result(s): Twenty-six of 1026 identified articles were selected evaluating 853 patients with CPP. The implantation rate after test-phase success was 64.3%. Significant improvement of pain scores was reported in 13 studies; three studies reported no significant change. WMD in pain scores on a 10-point scale was -4.64 (95% confidence interval [CI] = -5.32 to -3.95, p < 0.00001) across 20 studies which were quantitatively synthesized: effects were maintained at long-term follow-up. Mean follow-up was 42.5 months (0-59). Quality of life was measured by RAND SF-36 and EQ-5D questionnaires and all studies reported improvement in quality of life. One hundred and eighty-nine complications were reported in 1555 patients (Clavien-Dindo Grade I-IIIb). Risk of bias ranged from low to high risk. Studies were case series and bias stemmed from selection bias and loss to follow-up. Conclusion(s): Sacral Neuromodulation is a reasonably effective treatment of Chronic Pelvic Pain and significantly reduces pain and increases patients' quality of life with immediate to long-term effects.Copyright © 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

Greiman, A. K., et al. (2019). "Urethral diverticulum: A systematic review." Arab Journal of Urology 17(1): 49-57.
	Objective: To present a review of the current literature regarding the presentation, diagnosis, and treatment of female urethral diverticula (UD). Method(s): A systematic search of the PubMed database was performed to identify studies evaluating female UD. Article titles, abstracts and full-text manuscripts were screened to identify relevant studies, which then underwent data extraction and analysis. Result(s): In all, 50 studies evaluating the presentation, diagnosis and treatment of female UD were deemed relevant for inclusion. Almost all studies were retrospective single-arm case series. Female UD are outpouchings of the urethral lumen into the surrounding connective tissue. The presentation of female UD is diverse and can range from incidental findings to lower urinary tract symptoms, frequent urinary tract infections, dyspareunia, urinary incontinence (UI), or malignancy. Repair of UD begins with an accurate assessment and diagnosis, which should include adequate radiographic imaging, usually including magnetic resonance imaging. Once the diagnosis is confirmed, the usual treatment is surgical excision and reconstruction, most often through a transvaginal approach. The principles of transvaginal urethral diverticulectomy include: removal of the entire urethral diverticulum wall, watertight closure of the urethra, multi-layered and non-overlapping closure of surrounding tissue with absorbable suture, and preservation or creation of continence. Results of surgical repair are usually excellent, although long-term recurrence of these lesions may occur. Complications of urethral diverticulectomy include urethrovaginal fistula, UI, and rarely urethral stricture. Conclusion(s): Whilst urethral diverticulectomy excision and reconstruction is a challenging procedure, it is ultimately satisfying for the patient and the surgeon when relief of bothersome symptoms is achieved. Adherence to principles of reconstructive surgery is important to ensure a satisfactory result. Abbreviations: PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; UD: urethral diverticulum/diverticula; UI: urinary incontinence; US: ultrasonography; VCUG: voiding cystourethrogram.Copyright © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Griesinger, G., et al. (2020). "Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis." PloS One 15(11 November): e0241044.
	The aim of this systematic review and meta-analysis was to conduct a comprehensive assessment of the evidence on the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) for luteal phase support. Embase and MEDLINE were searched for studies that evaluated the effect of luteal phase support with daily administration of oral dydrogesterone (20 to 40 mg) versus MVP capsules (600 to 800 mg) or gel (90 mg) on pregnancy or live birth rates in women undergoing fresh-cycle IVF (protocol registered at PROSPERO [CRD42018105949]). Individual participant data (IPD) were extracted for the primary analysis where available and aggregate data were extracted for the secondary analysis. Nine studies were eligible for inclusion; two studies had suitable IPD (full analysis sample: n = 1957). In the meta-analysis of IPD, oral dydrogesterone was associated with a significantly higher chance of ongoing pregnancy at 12 weeks of gestation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.08 to 1.61; P = 0.0075) and live birth (OR, 1.28; 95% CI, 1.04 to 1.57; P = 0.0214) compared to MVP. A meta-analysis combining IPD and aggregate data for all nine studies also demonstrated a statistically significant difference between oral dydrogesterone and MVP (pregnancy: OR, 1.16; 95% CI, 1.01 to 1.34; P = 0.04; live birth: OR, 1.19; 95% CI, 1.03 to 1.38; P = 0.02). Safety parameters were similar between the two groups. Collectively, this study indicates that a higher pregnancy rate and live birth rate may be obtained in women receiving oral dydrogesterone versus MVP for luteal phase support.Copyright © 2020 Griesinger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Griesinger, G., et al. (2021). "Effect of the oxytocin receptor antagonist nolasiban on pregnancy rates in women undergoing embryo transfer following IVF: analysis of three randomised clinical trials." Human reproduction (Oxford, England) 36(4): 1007-1020.
	Study Question: Does a single oral dose of nolasiban 900 mg administered 4 h before embryo transfer (ET) increase pregnancy rates in women undergoing IVF?; Summary Answer: In an individual patient data (IPD) meta-analysis of three clinical trials, a single oral dose of nolasiban 900 mg was associated with an increased ongoing pregnancy rate of an absolute 5% (relative 15%).; What Is Known Already: Several clinical studies have shown that blocking activation of oxytocin receptors by an oxytocin receptor (OTR) antagonist has the potential to decrease uterine contractions, increase endometrial perfusion and enhance endometrial decidualisation and other parameters of endometrial receptivity. It has been hypothesised that antagonism of oxytocin receptors could improve the likelihood of successful embryo implantation and thus increase pregnancy and live birth rates following ET.; Study Design, Size, Duration: This is an analysis of three randomised, double-blind, placebo-controlled trials, which randomised 1836 subjects between 2015 and 2019. We describe the results of a meta-analysis of individual participant data (IPD) from all three trials and the pre-specified analyses of each individual trial.; Participant/material, Setting, Methods: Participants were patients undergoing ET following IVF/ICSI in 60 fertility centres in 11 European countries. Study subjects were below 38 years old and had no more than one previously failed cycle. They were randomised to a single oral dose of nolasiban 900 mg (n = 846) or placebo (n = 864). In IMPLANT 1, additional participants were also randomised to nolasiban 100 mg (n = 62) or 300 mg (n = 60). Fresh ET of one good quality embryo (except in IMPLANT 1 where transfer of two embryos was allowed) was performed on Day 3 or Day 5 after oocyte retrieval, approximately 4 h after receiving the study treatment. Serum hCG levels were collected at 14 days post oocyte retrieval (Week 2) and for women with a positive hCG result, ultrasound was performed at Week 6 post-ET (clinical pregnancy) and at Week 10 post-ET (ongoing pregnancy). Pregnant patients were followed for maternal (adverse events), obstetric (live birth, gestational age at delivery, type of delivery, incidence of twins) and neonatal (sex, weight, height, head circumference, Apgar scores, congenital anomalies, breast feeding, admission to intensive care and specific morbidities e.g. jaundice, respiratory distress syndrome) outcomes.; Main Results and the Role of Chance: In an IPD meta-analysis of the clinical trials, a single oral dose of nolasiban 900 mg was associated with an absolute increase of 5.0% (95% CI 0.5, 9.6) in ongoing pregnancy rate and a corresponding increase of 4.4% (95% CI -0.10, 8.93) in live birth rate compared to placebo. Similar magnitude increases were observed for D3 or D5 transfers but were not significantly different from the placebo. Population pharmacokinetics (PK) demonstrated a correlation between higher exposures and pregnancy.; Limitations, Reason for Caution: The meta-analysis was not a pre-specified analysis. While the individual trials did not show a consistent significant effect, they were not powered based on an absolute increase of 5% in ongoing pregnancy rate. Only a single dose of up to 900 mg nolasiban was administered in the clinical trials; higher doses or extended regimens have not been tested. Only fresh ET has been assessed in the clinical trials to date.; Wider Implications of the Findings: The finding support the hypothesis that oxytocin receptor antagonism at the time of ET can increase pregnancy rates following IVF. The overall clinical and population PK data support future evaluation of higher doses and/or alternate regimens of nolasiban in women undergoing ET following IVF.; Study Funding/competing Interests: The trials were designed, conducted and funded by ObsEva SA. A.H., O.P., E.G., E.L. are employees and stockholders of ObsEva SA. E.L. is a board member of ObsEva SA. G.G. reports honoraria and/or non-financial support from ObsEva, Merck, M D, Ferring, Abbott, Gedeon-Richter, Theramex, Guerbet, Finox, Biosilu, Preglem and ReprodWissen GmbH. C.B. reports grants and honoraria from ObsEva, Ferring, Abbott, Gedeon Richter and MSD. P.P. reports consulting fees from ObsEva. H.T. reports grants and or fees from ObsEva, Research Fund of Flanders, Cook, MSD, Roche, Gedeon Richter, Abbott, Theramex and Ferring. H.V. reports grants from ObsEva and non-financial support from Ferring. P.T. is an employee of Cytel Inc., who provides statistical services to ObsEva. J.D. reports consulting fees and other payments from ObsEva and, Scientific Advisory Board membership of ObsEva.; Trial Registration Numbers: ClinicalTrials.gov: NCT02310802, NCT03081208, NCT03758885.; Trial Registration Dates: December 2014 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885).; First Patient’s Enrolment: January 2015 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885). (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Griffith, T., et al. (2022). "The role for vaginal cuff brachytherapy boost after external beam radiation therapy in endometrial cancer." Brachytherapy 21(2): 177-185.
	Purpose: To evaluate the role and technique of a vaginal cuff brachytherapy (VB) boost to adjuvant external beam (EB) radiation for endometrial cancer through a systematic review.; Methods and Materials: Relevant trials were identified through a systematic search of the literature.; Results: A total of 21 prospective and retrospective studies which had a patient cohort undergoing EB + VB was identified to evaluate for rates of vaginal and pelvic recurrences, overall survival, and toxicity. Additional database studies were utilized to demonstrate differences in local control and overall survival between EB and EB + VB.; Conclusions: While there is limited prospective evidence to guide the use of a VB boost after EB, the evidence suggests that patients with a higher risk of a vaginal recurrence such as those with cervical stromal involvement in select Stage III patients may derive local control and survival benefits from a VB boost. Additional individual risk factors such as grade, histology, extent of invasion, margin status, age, and the use of lower doses of EB should be considered when deciding when to add a VB boost. (Published by Elsevier Inc.)

Grigolon Ruth, B., et al. (2023). "Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression." Menopause (New York, N.Y.) 30(1): 95-107.
	Importance: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population.; Objective: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years.; Evidence Review: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS.; Findings: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, -0.35 [95% confidence interval, -0.68 to -0.03; P = 0.0351]; AS: standardized mean difference, -0.74 [95% CI, -1.37 to -0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression.; Conclusions and Relevance: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.; Competing Interests: Financial disclosure/conflicts of interest: C.N.S. has received research funds from Otsuka, Eisai, Ontario Research Fund, and Ontario Brain Institute and acted as a consultant for Otsuka, Eisai, Pfizer, and Bayer. E.B. receives funding from PSI Foundation, Queen's University Faculty of Health Science, and Queen's University Department of Psychiatry. The other authors have nothing to disclose. (Copyright © 2022 by The North American Menopause Society.)

Grigore, M., et al. (2021). "Large ovarian tumors in adolescents, a systematic review of reported cases, diagnostic findings and surgical management." Taiwanese Journal of Obstetrics & Gynecology 60(4): 602-608.
	The purpose of this study was to analyze the published cases regarding large ovarian masses in adolescents, in order to find useful clinical implications for the diagnosis and management of the condition. The methodology employed a systematic review of reported cases of large/giant ovarian tumor in adolescence. The main objective was to assess the imagery findings, histology of the tumor, and the type of surgery performed. Our study included 58 patients with the tumor diameters ranged between 11 and 42 cm, with a median value of 22.75 cm and a mean diameter of 24.66 ± 8.50 cm. The lesions were benign in 47 cases (81%), borderline in 2 cases (3.4%), and malign in 9 cases (15.6%). We found no statistically significant difference (p > 0.05) between the size of the tumors and the ovarian markers levels. At the same time, a statistically significant difference was identified (p=<0,001) between elevated levels of the serum markers and the malignant tumor type (OR = 12.45; CI 95 = 2.55-94.77). The main types of surgery performed were cystectomy (35 cases), oophorectomy (4 cases), salpingo-oophorectomy (18 cases). Open laparotomy was performed in 46 cases on tumors with a median diameter of 25 ± 8.8 cm, while laparoscopy was done in 12 cases on tumors with a median diameter of 23.7 ± 7.6 cm. For optimal surgical management, it is advisable to assess first the imagery findings and tumor markers. Then, the laparoscopic approach should be considered as a feasible option, especially in cases where there are no predictive factors for a malign disease.; Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. (Copyright © 2021. Published by Elsevier B.V.)

Grigoryan, B., et al. (2023). "Adjustable slings versus other surgical methods in female stress urinary incontinence: a systematic review and meta-analysis." International Urogynecology Journal 34(7): 1351-1367.
	Introduction and hypothesis: The objective of this study was to evaluate the efficacy and safety of different adjustable slings compared to other surgical methods for the treatment of stress urinary incontinence (SUI) among women. Method(s): The inclusion criteria were as follows: randomized controlled trials (RCTs) and non-RCTs assessing adult women with SUI. The exclusion criteria were as follows: other types of urinary incontinence, studies that combined conservative interventions and pharmacological treatment, pregnant and lactating patients. Databases were searched up to November 2022 to identify articles evaluating the effectiveness and safety of different adjustable slings compared to other surgical methods for the treatment of SUI among women. The systematic review was conducted in accordance with the PRISMA 2020 checklist and registered in PROSPERO. Risk-of-bias assessment tools recommended by the Cochrane Society were used to evaluate the risk of bias in the included studies. Result(s): Eighteen clinical trials were included in this systematic review, and 11 studies were included in the meta-analysis. Fourteen studies were RCTs, and four were retrospective studies. Only RCTs were included in the meta-analyses. There was no statistically significant difference in the objective cure rate, subjective cure rate, or long-term postoperative complication rate between Ajust single-incision mini-slings (SIMS) and standard mid-urethral slings (SMUS) or MiniArc SIMS. However, the operation time in the adjustable SIMS group was significantly shorter (RR = -4.20, 95% CI: [-7.51, -0.89], p = 0.01). Conclusion(s): This systematic review and meta-analysis revealed that adjustable SIMS is equally effective when compared with SMUS for the treatment of SUI among women. Moreover, the operation time for the adjustable SIMS was shorter. However, additional well-designed studies with standard outcome measures and complete follow-up periods will help to increase confidence in the choice of different options for treating SUI among women.Copyright © 2023, The International Urogynecological Association.

Grilli, D., et al. (2023). "Combined treatment with vaginal native tissue repair plus mid-urethral sling or pelvic floor muscle training in patients with anterior defect and occult stress urinary incontinence: quality of life and sexual function analysis." Minerva Obstetrics and Gynecology.
	BACKGROUND: The aim of this study was to compare the efficacy of vaginal native tissue repair (VNTR) combined with tension-free transobturator tape (TVT-O) or pelvic floor muscle training (PFMT) in terms of quality of life (QoL) and sexual function (SF) in women affected by anterior defect and occult stress urinary incontinence (OSUI). METHOD(S): One hundred forty-seven patients with symptomatic anterior defect with OSUI underwent VNTR. In 71 patients TVT-O was inserted and 76 underwent PFMT after surgery. Clinical exam, 3-day voiding diary and urodynamic testing were evaluated in preoperative and postoperative times. Specific questionnaires were also administered, in order to indagate disease perception and the impact on QoL and SF. RESULT(S): Nine patients had postoperative pain in the TVT-O group vs. 0 patients in the PMFT group (P=0.001) and 7 patients reported de novo urgency vs. 3 in the two groups, respectively. At 12 weeks follow-up (FU), the first voiding desire was at 88.12+19.70 mL in VNTR+TOT vs. 102.29+19.13 (P=0.03); the mean number of voids (24 hours) was 9.95+/-2.66 vs. 6.14+/-1.77 (P=0.04), respectively. No significant differences in terms of QoL and SF were shown. CONCLUSION(S): This retrospective study suggests that VNTR+TVT-O and VNTR+PMFT have the same efficacy in terms of QoL and SF, with several post-operative complications, even if minor, in patients treated with combined surgery.

Grimes Cara, L., et al. (2019). "Surgical interventions for posterior compartment prolapse and obstructed defecation symptoms: a systematic review with clinical practice recommendations." International Urogynecology Journal 30(9): 1433-1454.
	Introduction and Hypothesis: Several posterior compartment surgical approaches are used to address posterior vaginal wall prolapse and obstructed defecation. We aimed to compare outcomes for both conditions among different surgical approaches.; Methods: A systematic review was performed comparing the impact of surgical interventions in the posterior compartment on prolapse and defecatory symptoms. MEDLINE, Embase, and ClinicalTrials.gov were searched from inception to 4 April 2018. Randomized controlled trials, prospective and retrospective comparative and single-group studies of women undergoing posterior vaginal compartment surgery for vaginal bulge or bowel symptoms were included. Studies had to include both anatomical and symptom outcomes both pre- and post-surgery.; Results: Forty-six eligible studies reported on six surgery types. Prolapse and defecatory symptoms improved with native-tissue transvaginal rectocele repair, transanal rectocele repair, and stapled transanal rectocele repair (STARR) surgeries. Although prolapse was improved with sacrocolpoperineopexy, defecatory symptoms worsened. STARR caused high rates of fecal urgency postoperatively, but this symptom typically resolved with time. Site-specific posterior repairs improved prolapse stage and symptoms of obstructed defecation. Compared with the transanal route, native-tissue transvaginal repair resulted in greater improvement in anatomical outcomes, improved obstructed defecation symptoms, and lower chances of rectal injury, but higher rates of dyspareunia.; Conclusions: Surgery in the posterior vaginal compartment typically has a high rate of success for anatomical outcomes, obstructed defecation, and bulge symptoms, although these may not persist over time. Based on this evidence, to improve anatomical and symptomatic outcomes, a native-tissue transvaginal rectocele repair should be preferentially performed.

Grinstein, E., et al. (2022). "Long term outcomes of laparoscopic sacro/colpo-hysteropexy with and without rectopexy for the treatment of prolapse." International Urogynecology Journal 33(2): 343-350.
	Introduction and Hypothesis: Laparoscopic sacrohysteropexy (LSH), sacrocolpopexy (LSC) and ventral rectopexy (LVR) with mesh are advocated for surgical treatment of pelvic and rectal prolapse. Our study aims at showing the feasibility of concomitant laparoscopic prolapse repair by comparing perioperative and long-term outcomes of LSH or LSC with and without LVR.; Methods: This is a retrospective study carried out on 348 women operated on between July 2009 and July 2019. Patients were divided into four groups: (1) LSH only, (2) LSC only, (3) LSH + LVR and (4) LSC + LVR. POP-Q scores and satisfaction questionnaires were recorded at baseline and then annually. Outcomes were defined as subjective failure (vaginal/rectal prolapse symptoms), objective failure (prolapse to/beyond the hymen, full thickness rectal prolapse) or retreatment for prolapse. Complications were collected and graded according to the Clavien-Dindo classification.; Results: Three hundred forty-eight women underwent laparoscopic repair for pelvic and rectal prolapse (219, 44, 66 and 19 in group 1, 2, 3 and 4, respectively). Median follow-up was 24 (4-174) months. Success rate for both rectal and pelvic prolapse was 90.2%. Recurrence rates were not significantly different between the groups (12.3%, 6.8%, 9.1% and 10.5% for groups 1, 2, 3 and 4, respectively). Significant improvement was noticed in satisfaction questionnaires in all groups. There was no difference in perioperative and late complications.; Conclusion: The combined laparoscopic procedure appears to be safe and efficient in treating pelvic and rectal prolapse. Appropriate patient selection and available surgical expertise should determine whether to perform these procedures combined or separately. (© 2021. The International Urogynecological Association.)

Grisham Rachel, N. and M. H. Chui (2022). "Advancements in Low-Grade Serous Carcinoma of the Ovary and Peritoneum." Current oncology reports 24(11): 1549-1555.
	Purpose of Review: Low-grade serous ovarian cancer (LGSOC) is a rare form of epithelial ovarian cancer that generally exhibits a protracted course and is less sensitive to chemotherapy than high-grade serous ovarian cancer. Over the past decade, it has become clear that patients with LGSOC have a clinically distinct course and are molecularly and histologically unique from patients with high-grade serous ovarian cancer.; Recent Findings: Endocrine therapy is frequently used for the treatment of patients with recurrent LGSOC and is now also part of the standard upfront treatment of this disease, with an ongoing phase III clinical trial seeking to determine if chemotherapy can be eliminated altogether from the initial treatment of LGSOC. Tumors are frequently found to exhibit alterations affecting the mitogen-activated protein kinase (MAPK) pathway, recently leading to developments in the use of targeted treatments for those patients with recurrent disease. LGSOC is a clinically, histologically, and molecularly unique form of epithelial ovarian cancer. Recent advances in the understanding of endocrine and molecular drivers of this disease have led to changes in both the treatment of newly diagnosed and recurrent disease, with ongoing studies focused on refining upfront therapy and seeking novel targeted combinations for those patients with recurrent disease. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Grisham Rachel, N., et al. (2023). "The highs and lows of serous ovarian cancer." Cancer 129(17): 2613-2620.
	Low-grade serous ovarian cancer was initially described as a distinct type of rare epithelial ovarian cancer 20 years ago; however, only recently have physicians begun to leverage the understanding of the clinical behavior and molecular profile of this disease for treatment. The use of routine next-generation sequencing has allowed a deeper understanding of the molecular drivers of this disease and shown how molecular alterations in mitogen-activated protein kinase pathway genes such as KRAS and BRAF can affect overall prognosis and disease behavior. The use of targeted therapies, including MEK inhibitors, BRAF kinase inhibitors, and other investigational targeted therapies are changing the way this disease is viewed and treated. In addition, endocrine therapy can provide prolonged disease stability with generally mild toxicity, as well as promising response rates in recent studies examining combination therapy with CDK 4/6 inhibitors in the upfront and recurrent setting. Once seen merely as a chemo-resistant form of ovarian cancer, recent studies have worked to harness the unique features of low-grade serous ovarian cancer to provide individualized treatment options for patients with this disease. (© 2023 American Cancer Society.)

Group, A. and Gineco (2022). Niraparib With beVAcizumab After Complete cytoreductioN in Patients With ovArian Cancer.
	No Results Available Drug: Chemotherapy|Drug: Bevacizumab-Awwb|Drug: Niraparib Progression-Free survival (PFS) rate up to 24 months|PFS2|Number of Participants with abnormal physical examinations, abnormal vital signs and abnormal findings according to CTC-AE v5|Time to First Subsequent Treatment|Time to Second Subsequent Treatment|Long-term Overall Survival in both arms|Confirmation of the predictive value (overall chemo-sensitivity) of the KELIM. Female Phase 2 390 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GINECO-OV129b February 2030

Group, A., et al. (2022). Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line.
	No Results Available Drug: Carboplatin-Paclitaxel|Drug: Dostarlimab Progression Free Survival (PFS)|Overall Survival (OS) (key secondary endpoint)|Progression Free Survival 2 (PFS2)|Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version)|To assess the effects of Dostarlimab on Health related quality of Life (QoL) based on EORTC QLQ C30 (Quality of Life questionnaire-core 30)|To assess the quantity of peripheral neuropathy event induced by chemotherapy based on EORTC QLQ-CIPN 20 (Quality of Life questionnaire-Chemotherapy induced peripheral neuropathy 20)|To assess the effects of treatment on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, based EORTC QLQ-EN24 (Quality of Life Questionnaire - Endometrial Cancer Module)|To assess the status of health for patients with endometrial cancer based on EUROQOL EQ-5D (Descriptive system)|Best Objective Response Rate (ORR)|Disease Control Rate (DCR)|Duration of Response Rate (DoR)|Safety and number of adverse events|Tolerability to the treatment|Time to first and second Subsequent Treatment|To determine the immunogenicity of dostarlimab Female Phase 3 260 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GINECO-EN105b October 2029

Group, A., et al. (2021). OSE2101 Alone or in Combination With Pembrolizumab vs BSC in Patient With Platinum-sensitive Recurrent OC.
	No Results Available Drug: OSE2101|Drug: Pembrolizumab 25 MG/ML [Keytruda] Progression free survival (PFS)|Objective response rate (ORR)|Incidence of treatment emergent adverse events|Time to subsequent first treatments (TTST-1)|Time to subsequent second treatments (TTST-2)|Overall Survival (OS) Female Phase 2 180 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GINECO-OV244b|2020-004364-25|ENGOT-ov58 December 2025

Group, A. G. O. S. and T. Groups European Network of Gynaecological Oncological (2022). Niraparib vs Niraparib Plus Bevacizumab in Patients With Platinum/Taxane-based Chemotherapy in Advanced Ovarian Cancer.
	No Results Available Drug: Carboplatin|Drug: Paclitaxel|Drug: Bevacizumab|Drug: Niraparib Progression Free Survival (PFS)|PFS according to tumor BRCA status|Overall Survival (OS)|Time to First Subsequent Therapy (TFST)|Second Progression (PFS 2)|Time to Second Subsequent Therapy (TSST)|Number of participants with treatment-related adverse events (AE) and/or serious adverse events (SAEs) and/or AEs that led to premature withdrawal of trial treatment and/or interruptions/dose modifications|Effects on Quality of Life (QoL) Female Phase 3 970 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment AGO-OVAR 28|2021-001271-16|ENGOT-ov57 September 2030

Group Australia New Zealand Gynaecological, O., et al. (2023). EPOCH: Eribulin and Pembrolizumab in Ovarian/Uterine Carcinosarcoma.
	No Results Available Drug: Eribulin Mesylate|Drug: Pembrolizumab Clinical Benefit Rate (CBR) by RECIST v1.1 in combination therapy arm|Clinical Benefit Rate (CBR) by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in single agent therapy arm|Objective Response Rate (ORR) in both the single agent eribulin and combination eribulin/pembrolizumab arms|Clinical Benefit Rate (CBR) by iRECIST (modified RECIST guidelines for use in cancer immunotherapy trials)|Time to progression in the combination therapy arm|Progression free survival (PFS)|Overall Survival (OS)|Adverse events|Health related Quality of Life using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for cancer patients (QLQ C30)|Health related Quality of Life using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire module for Ovarian Cancer patients (OV28) All Phase 2 30 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ANZGOG 1828/2021 December 2026

Group Canadian Cancer, T., et al. (2022). Immunotherapy Platform Study in Platinum Resistant High Grade Serous Ovarian Cancer.
	No Results Available Drug: Durvalumab|Drug: BA3011|Drug: BA3021|Drug: To be determined To efficiently identify based on objective response rate (ORR), by investigator assessment using RECIST 1.1, promising immunotherapy combinations for the treatment of high grade serous ovarian cancer for later validation in randomized trials|Evaluate ORR by investigator assessment using RECIST 1.1|Determine progression-free survival of immunotherapy regimens (RECIST 1.1 and iRECIST)|Determine overall-survival of immunotherapy regimens (RECIST 1.1 and iRECIST)|Number and severity of adverse events Female Phase 2 60 Other|Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment I240 June 2025

Group, S. B. C. R. and Novartis (2021). Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients With PD1-high mRNA Expressing Tumors.
	No Results Available Drug: Spartalizumab|Drug: Tislelizumab Overall Response rate (ORR) (Cohort 3)|Clinical Benefit Rate (CBR) in patients with high mRNA PD1 expressing tumors (Cohort 3)|Progression free survival (PFS) in patients with high mRNA PD1 expressing tumors (Cohort 3)|Duration of response (DoR) in patients with high mRNA PD1 expressing tumors (Cohort 3)|Time to response (TtR) in patients with high mRNA PD1 expressing tumors (Cohort 3)|Overall survival (OS) in patients with high mRNA PD1 expressing tumors (Cohort 3)|PFS compared to PFS on prior line of therapy (pre-PFS) in patients with high mRNA PD1 expressing tumors (Cohort 3)|ORR in patients with low mRNA PD1-expressing tumors (Cohorts 1 and 2)|CBR in patients with low mRNA PD1 expressing tumors (Cohorts 1 and 2)|PFS in patients with low mRNA PD1 expressing tumors (Cohorts 1and 2)|DoR in patients with low mRNA PD1 expressing tumors (Cohorts 1and 2)|TtR in patients with low mRNA PD1 expressing tumors (Cohorts 1 and 2)|OS in patients with low mRNA PD1 expressing tumors (Cohorts 1 and 2)|PFS compared to PFS on prior line of therapy (pre-PFS) in patients with low mRNA PD1 expressing tumors (Cohorts 1 and 2)|Incidence, seriousness, treatment-related and intensity of Treatment Emergent Adverse Events All Phase 2 184 Other|Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ACROPOLI (SOLTI-1904) March 31, 2027

Grushina, T. I. and I. I. Orlov (2022). "[Shock wave therapy in oncology: in vitro, in vivo, rehabilitation]." Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury 99(3): 58-65.
	Extracorporeal shock wave therapy (ESWT) is a relatively new branch of physiotherapy.; Purpose of the Study: Conduct an analytical review of the available literature data on the use of ESWT in oncology.; Material and Methods: A review was conducted, including data from electronic databases: Scopus, Web of Science, MedLine, World Health Organization, The Cochrane Central Register of Controlled Trials, ScienceDirect, US National Library of Medicine National Institutes of Health, PubMed, Google Scholar, elibrary, CyberLeninka, disserCat.; Results and Conclusion: The study of ESWT in oncology is carried out in two directions: 1) impact on the tumor with the aim of its disintegration, inhibition of growth, enhancement of the action of radiation and/or chemotherapy; 2) rehabilitation of cancer patients. Shock waves in vitro and in vivo significantly reduce the viability and activate apoptosis of cell lines of osteosarcoma, cancer of the stomach, colon, rectum, bladder, breast, urothelial cancer of the upper urinary tract, adenocarcinoma of the cervix, Burkitt's lymphoma, sarcoma, anaplastic thyroid cancer glands, glioblastoma multiforme. Shock waves also sensitize tumor cells for adjuvant chemotherapy and increase its antitumor activity. The lack of a stimulating effect on a number of malignant tumors in this physical factor makes it possible to conduct ESWT studies in the rehabilitation of cancer patients. The data obtained by a number of authors indicate the clinical efficacy of ESWT in the rehabilitation of patients with erectile dysfunction after radical prostatectomy, with postmastectomy lymphedema of the upper limb, with myofascial pain syndrome after cervical lymph node dissection due to malignant neoplasms of the head and neck, with peripheral polyneuropathy induced by cytostatics. However, in order to develop indications and contraindications for the appointment of ESWT in the rehabilitation of cancer patients, it is not enough just to evaluate its clinical effectiveness; currently absent scientific studies with long-term follow-up of patients who received this method of physiotherapy are needed.

Grzyb, K., et al. (2022). "Effect of Equal Volume, High-Repetition Resistance Training to Volitional Fatigue, With Different Workout Frequencies, on Muscle Mass and Neuromuscular Performance in Postmenopausal Women." Journal of strength and conditioning research 36(1): 31-36.
	Abstract: Grzyb, K, Candow, DG, Schoenfeld, BJ, Bernat, P, Butchart, S, and Neary, JP. Effect of equal volume, high-repetition resistance training to volitional fatigue, with different workout frequencies, on muscle mass and neuromuscular performance in postmenopausal women. J Strength Cond Res 36(1): 31-36, 2022-This study examined the effects of equal volume, high-repetition resistance training (HRRT) performed to volitional fatigue, with different workout frequencies, on muscle mass and neuromuscular performance (strength, endurance) in untrained postmenopausal women. Subjects were randomized to perform HRRT 2 d·wk-1 (HRRT-2; 3 sets of 20-30 repetitions/set for elbow and knee flexion and extension) or 3 d·wk-1 (HRRT-3; 2 sets of 20-30 repetitions/set per exercise) for 8 weeks. Baseline and post-training assessments were made for muscle thickness, strength (1 repetition maximum [1RM]) and endurance (number of repetitions performed at 50% baseline 1RM) for elbow and knee flexor and extensor muscle groups. Significance was set at p < 0.05. There was a significant increase over time for all measures of muscle thickness, strength, and endurance (p < 0.005), with no differences between groups. Untrained postmenopausal women can expect to achieve similar improvements in muscle size, strength, and endurance when training 2 or 3 days per week, provided total weekly training volume is equal. (Copyright © 2020 National Strength and Conditioning Association.)

Grzybowska, M. E., et al. (2022). "Colpocleisis as an obliterative surgery for pelvic organ prolapse: is it still a viable option in the twenty-first century? Narrative review." International Urogynecology Journal 33(1): 31-46.
	Introduction and hypothesis: The aims were to review the literature from the last two decades and analyze treatment efficacy and findings of the studies on colpocleisis. Method(s): A systematic search was conducted within the MEDLINE/PubMed and ClinicalTrials.gov databases, using the following keywords: pelvic organ prolapse (POP), colpocleisis, obliterative, and LeFort. All English full-text prospective and retrospective observational and interventional studies were included. Anatomical and subjective success, surgical techniques, concomitant procedures, complication rates, anesthesia methods, and decision regret were analyzed. Result(s): A total of 237 papers were identified and 49 met the inclusion criteria. Mean patient age was 69.0 +/- 8.0 to 84 +/- 3.1. Over 90.2% of patients undergoing colpocleisis were diagnosed with POP stage >= 3. The follow-up ranged from 30 days to a median of 5 years. Anatomical success, defined as POP-Q stage <= 1 and no prolapse beyond the hymen, was achieved in 62.5 to 100% and 87.5 to 100% of all patients respectively. Subjective success ranged from 88% to 100%. Regret over the loss of coital ability ranged from 0% in many studies to 12.9%, general decision regret from 0% to 13.8%. After concomitant midurethral sling surgery, 86.8% to 94% of all patients were continent, with a 0-14% sling revision rate due to urinary retention. Urinary tract infection was the most common postoperative complication (4.3 to 9% confirmed with urine culture, 34.7% based on symptom definition). Bowel (0 to 2.7%) and urinary tract (0 to 9.1%) injuries were the consequences of concomitant procedures. The mortality rates were up to 1.3%. Conclusion(s): Colpocleisis is a heterogeneous procedure, characterized by high subjective and objective success, low coital ability regret, and a low risk of complications.Copyright © 2021, The Author(s).

Gu, M., et al. (2022). "Effect on the cardiovascular independent risk factor lipoprotein(a) in overweight or obese PCOS patients with ethinyl-estradiol/drospirenone alone or plus orlistat." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(7): 598-602.
	Objective: This study aimed to assess the effect on the cardiovascular independent risk factor Lipoprotein(a) [Lp(a)] in overweight or obese polycystic ovary syndrome (PCOS) patients with ethinyl-estradiol/drospirenone (EE/DRSP) alone or plus orlistat.; Methods: In this randomized controlled prospective study, 66 PCOS patients with overweight or obesity were matched according to age and BMI. All participants were randomly divided into two groups to receive EE/DRSP plus Orlistat ( n = 33) or EE/DRSP alone ( n = 33) for 3 months. Changes in cardiovascular risk factors including Lp(a), CRP, LDL-C, anthropometric assessments, variations in sex hormones related parameters, and in glucolipid metabolic index were evaluated after the intervention.; Results: Lp(a) and CRP were significantly decreased at 3 months only in the EE/DRSP plus Orlistat group. There were significant reductions in LDL-C, weight, BMI, waist circumference (WC), body fat percentage (BFP), FT in both groups compared to baseline. However, these reductions were significantly greater in EE/DRSP plus Orlistat group. The levels of HDL-C, TG, and SHBG significantly increased, while TT and LH significantly decreased in both groups over time. TC, FINS, FPG were not significantly changed in both groups after the intervention.; Conclusions: This is the first study found that EE/DRSP plus Orlistat could significantly decrease Lp(a) in overweight or obese PCOS patients. This result can be assessed as particularly important, because Lp(a) is well-known as an independent risk factor predicting an increased risk of cardiovascular diseases (CVDs).

Gu, Y., et al. (2021). "Operative and Oncological Outcomes Comparing Sentinel Node Mapping and Systematic Lymphadenectomy in Endometrial Cancer Staging: Meta-Analysis With Trial Sequential Analysis." Frontiers in Oncology 10: 580128.
	Objective: To evaluate the utility of sentinel lymph node mapping (SLN) in endometrial cancer (EC) patients in comparison with lymphadenectomy (LND).; Methods: Comprehensive search was performed in MEDLINE, EMBASE, CENTRAL, OVID, Web of science databases, and three clinical trials registration websites, from the database inception to September 2020. The primary outcomes covered operative outcomes, nodal assessment, and oncological outcomes. Software Revman 5.3 was used. Trial sequential analysis (TSA) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were performed.; Results: Overall, 5,820 EC patients from 15 studies were pooled in the meta-analysis: SLN group (N = 2,152, 37.0%), LND group (N = 3,668, 63.0%). In meta-analysis of blood loss, SLN offered advantage over LND in reducing operation bleeding (I 2 = 74%, P<0.01). Z-curve of blood loss crossed trial sequential monitoring boundaries though did not reach TSA sample size. There was no difference between SLN and LND in intra-operative complications (I 2 = 7%, P = 0.12). SLN was superior to LND in detecting positive pelvic nodes (P-LN) (I 2 = 36%, P<0.001), even in high risk patients (I 2 = 36%, P = 0.001). While no difference was observed in detection of positive para-aortic nodes (PA-LN) (I 2 = 47%, P = 0.76), even in high risk patients (I 2 = 62%, P = 0.34). Analysis showed no difference between two groups in the number of resected pelvic nodes (I 2 = 99%, P = 0.26). SLN was not associated with a statistically significant overall survival (I 2 = 79%, P = 0.94). There was no difference in progression-free survival between SLN and LND (I 2 = 52%, P = 0.31). No difference was observed in recurrence. Based on the GRADE assessment, we considered the quality of current evidence to be moderate for P-LN biopsy, low for items like blood loss, PA-LN positive.; Conclusion: The present meta-analysis underlines that SLN is capable of reducing blood loss during operation in regardless of surgical approach with firm evidence from TSA. SLN mapping is more targeted for less node dissection and more detection of positive lymph nodes even in high risk patients with conclusive evidence from TSA. Utility of SLN yields no survival detriment in EC patients.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Gu, Cheng, Zong, Kong and Xiang.)

Gu, Y., et al. (2024). "The benefits and risks of menopause hormone therapy for the cardiovascular system in postmenopausal women: a systematic review and meta-analysis." BMC Women's Health 24(1): 60.
	Background: Menopause hormone therapy (MHT), as an effective method to alleviate the menopause-related symptoms of women, its benefits, risks, and potential influencing factors for the cardiovascular system of postmenopausal women are not very clear. Objective(s): To evaluate cardiovascular benefits and risks of MHT in postmenopausal women, and analyze the underlying factors that affect both. Search strategy: The EMBASE, MEDLINE, and CENTRAL databases were searched from 1975 to July 2022. Selection Criteria: Randomized Clinical Trials (RCTs) that met pre-specified inclusion criteria were included. Data Collection and Analysis: Two reviewers extracted data independently. A meta-analysis of random effects was used to analyze data. Main Result(s): This systematic review identified 33 RCTs using MHT involving 44,639 postmenopausal women with a mean age of 60.3 (range 48 to 72 years). There was no significant difference between MHT and placebo (or no treatment) in all-cause death (RR = 0.96, 95%CI 0.85 to 1.09, I2 = 14%) and cardiovascular events (RR = 0.97, 95%CI 0.82 to 1.14, I2 = 38%) in the overall population of postmenopausal women. However, MHT would increase the risk of stroke (RR = 1.23, 95%CI 1.08 to 1.41,I2 = 0%) and venous thromboembolism (RR = 1.86, 95%CI 1.39 to 2.50, I2 = 24%). Compared with placebo, MHT could improve flow-mediated arterial dilation (FMD) (SMD = 1.46, 95%CI 0.86 to 2.07, I2 = 90%), but it did not improve nitroglycerin-mediated arterial dilation (NMD) (SMD = 0.27, 95%CI - 0.08 to 0.62, I2 = 76%). Compared with women started MHT more than 10 years after menopause, women started MHT within 10 years after menopause had lower frequency of all-cause death (P = 0.02) and cardiovascular events (P = 0.002), and more significant improvement in FMD (P = 0.0003). Compared to mono-estrogen therapy, the combination therapy of estrogen and progesterone would not alter the outcomes of endpoint event. (all-cause death P = 0.52, cardiovascular events P = 0.90, stroke P = 0.85, venous thromboembolism P = 0.33, FMD P = 0.46, NMD P = 0.27). Conclusion(s): MHT improves flow-mediated arterial dilation (FMD) but fails to lower the risk of all-cause death and cardiovascular events, and increases the risk of stroke and venous thrombosis in postmenopausal women. Early acceptance of MHT not only reduces the risk of all-cause death and cardiovascular events but also further improves FMD, although the risk of stroke and venous thrombosis is not reduced. There is no difference in the outcome of cardiovascular system endpoints between mono-estrogen therapy and combination therapy of estrogen and progesterone.Copyright © 2024, The Author(s).

Gu, Y. and G. Liang (2021). "Application value of remifentanil combined with propofol anesthesia in painless artificial abortion." 医学临床研究 38(7): 1079‐1081.
	Objective: To observe the effect of remifentanil anesthesia in painless induced abortion and the effect of interleukin‐6 (IL‐6), γ‐interferon (IFN‐γ) and nuclear factor κB (NF‐κB) levels in patients. influences. Methods: A total of 146 patients with painless abortion who were admitted to our hospital were divided into observation group (remifentanil plus propofol scheme) and control group (propofol scheme) according to the corresponding anesthesia scheme, with 73 cases in each group. The intraoperative anesthesia effect and Ramsay sedation score at 6 hours after operation were compared between the two groups, and the changes of IL‐6, IFN‐γ, and NF‐κB levels before and after anesthesia were compared. Results: The excellent and good rate of anesthesia in the observation group was 93.15% (68/73), which was significantly higher than 89.04% (63/73) in the control group, and there was a significant difference between the two groups (P<0.05). The level of IFN‐γ was lower than that before anesthesia, while the levels of IL‐6 and NF‐kB were increased (P<0.05), and the improvement in the observation group was more obvious than that in the control group (P<0.05). Conclusion: The addition of remifentanil to patients with painless abortion can achieve better anesthesia effect, and the serum levels of IFN‐γ, IL‐6 and NF‐κB can also be effectively improved. postoperative pain level.

Guan, J. and X.-J. Chen (2022). "The present status of metformin in fertility-preserving treatment in atypical endometrial hyperplasia and endometrioid endometrial cancer." Frontiers in Endocrinology 13: 1041535.
	Progestin therapy is the main fertility-sparing treatment for women with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). However, still 15-25% of these women failed to achieve complete response (CR) and then lost their fertility after definitive surgery. Metformin has been demonstrated to play an anti-cancer role in multiple cancers including EC. Several studies also suggested metformin had potential benefit in improving the therapeutic outcome of fertility-preserving treatment alongside with progestin. This review has discussed existed evidence regarding the effect of metformin combined with progestin for women with AEH and EC who desire childbearing. Nevertheless, the therapeutic effect of metformin varied in different studies due to the high heterogeneity in the patient's characteristics, the inconsistency in dose and treatment duration of metformin, the combined use of hysteroscopy, the insufficient sample size and underpowered study-design. Therefore, care should be taken when interpreting the current results on this issue. Till now, there is still no strong evidence supporting the use of metformin in fertility-preserving treatment in AEH and EEC patients. Further research is needed to provide high-quality data to validate the role of metformin as adjunctive therapy alongside with progestin to preserve fertility for AEH and EEC patients.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Guan and Chen.)

Guan, Y. and J. Han (2024). "Quality-of-life improvements in patients after various surgical treatments for pelvic organ prolapse." Archives of Gynecology and Obstetrics 309(3): 813-820.
	Objective: To compare the improvements in quality of life of patients with pelvic organ prolapse (POP) treated using various surgical methods. Material(s) and Method(s): The PUBMED, MEDLINE and Cochrane Library online databases were searched using the keywords "pelvic organ prolapse", "surgery", "PFDI-20" and "PFIQ-7" for articles published from January 2010 to December 2022 that included quality-of-life scores before and after surgery. Result(s): Forty-nine articles were include. The mean postoperative PFDI-20 and PFIQ-7 scores decreased by 67.50% and 76.98%, respectively, compared with those before surgery. In 76.9% of patients, this change did not decrease with increased postoperative time. The improvement rate in PFDI-20 scores after colpocleisis did not differ statistically from that after sacrocolpopexy and was significantly higher than that after other procedures. The improvement rate in PFIQ-7 scores after colpocleisis did not statistically differ from that after high uterosacral ligament suspension and was significantly higher than that after other procedures. The improvement rate in PFDI-20 scores after transvaginal mesh-based repair (TVM) did not significantly differ from that after sacrospinous ligament fixation and was significantly lower than that after other procedures except traditional vaginal wall repair. The improvement rate in PFIQ-7 scores after TVM did not significantly differ from that after new procedures and was significantly lower than that after other procedures. Conclusion(s): Surgical treatment can significantly improve the quality of life of patients with POP. Colpocleisis may offer more advantages than those of other surgical procedures, and improvement was lower after TVM than after other procedures.Copyright © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023.

Guarano, A., et al. (2023). "Alpha Lipoic Acid Efficacy in PCOS Treatment: What Is the Truth?" Nutrients 15(14).
	Polycystic ovary syndrome (PCOS) is among the most common female endocrinopathies, affecting about 4-25% of women of reproductive age. Women affected by PCOS have an increased risk of developing metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and endometrial cancer. Given the pivotal role of insulin resistance (IR) in the pathogenesis of PCOS, in the last years, many insulin-sensitizing factors have been proposed for PCOS treatment. The first insulin sensitizer recommended by evidence-based guidelines for the assessment and treatment of PCOS was metformin, but the burden of side effects is responsible for treatment discontinuation in many patients. Inositols have insulin-mimetic properties and contribute to decreasing postprandial blood glucose, acting by different pathways. ALA is a natural amphipathic compound with a very strong anti-inflammatory and antioxidant effect and a very noteworthy role in the improvement of insulin metabolic pathway. Given the multiple effects of ALA, a therapeutic strategy based on the synergy between inositols and ALA has been recently proposed by many groups with the aim of improving insulin resistance, reducing androgen levels, and ameliorating reproductive outcomes in PCOS patients. The purpose of this study is to review the existing literature and to evaluate the existing data showing the efficacy and the limitation of a treatment strategy based on this promising molecule. ALA is a valid therapeutic strategy applicable in the treatment of PCOS patients: Its multiple actions, including antinflammatory, antioxidant, and insulin-sensitizing, may be of utmost importance in the treatment of a very complex syndrome. Specifically, the combination of MYO plus ALA creates a synergistic effect that improves insulin resistance in PCOS patients, especially in obese/overweight patients with T2DM familiarity. Moreover, ALA treatment also exerts beneficial effects on endocrine patterns, especially if combined with MYO, improving menstrual regularity and ovulation rhythm. The purpose of our study is to review the existing literature and to evaluate the data showing the efficacy and the limitations of a treatment strategy based on this promising molecule.

Guberti, M., et al. (2021). "Bovine colostrum applications in sick and healthy people: A systematic review." Nutrients 13(7): 2194.
	Colostrum is the first secretion of mammalian glands during the early period after birth giving. Its components are biologically active and have beneficial effects on new-born growth and well-being. Bovine colostrum has the highest concentration of these substances and its supplementation or application may provide health benefits. This systematic review was conducted to update current knowledge on bovine colostrum effects including all administration routes on healthy and sick subjects. Full texts or abstracts of twenty-eight papers as reports of systematic reviews, randomized controlled trials, observational studies and case series were included after searches in Medline, Embase, Cochrane Library and Cinahl databases. The full texts of selected studies were assessed for quality using validated tools and their results were summarized in different categories. Studies were highly heterogeneous as regards to population, intervention, outcome and risk of bias. Bovine colostrum topical application was shown effective on vaginal dryness related symptoms limitation. Its use as food supplement showed interesting effects preventing upper respiratory illness in sportsmen, modulating immune system response and reducing intestinal permeability in healthy and sick subjects. Conflicting results were provided in pediatric population and little evidence is available on its use with older adults. Further studies are mandatory to better understand all factors influencing its activity.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Guducu, N. and N. K. Ozcan (2023). "The effect of emotional freedom techniques (EFT) on postpartum depression: A randomized controlled trial." Explore 19(6): 842-850.
	This study examines the effect of EFT on postpartum depression, investigating EFT as a therapeutic method that is easy to apply and carries no cost as a preventive treatment for depression in pregnancy and postpartum depression. Based on prior research, we hypothesized that depressive symptoms would reduced by using EFT during pregnancy and the postpartum period. Secondly, we hypothesized that EFT could be used to reduce anxiety during pregnancy and the postpartum period. Thirdly, we hypothesized that using EFT to cope with stress during pregnancy and the postpartum period increases the use of active tools (seeking social support, being positive, and being self-confident), and finally, we hypothesized that the effect of EFT when applied during pregnancy to reduce depressive symptoms persists for a long time. Section snippets Study design The Consolidated Standards of Reporting Trials (CONSORT) 2018 instructions were followed in this randomized controlled, intervention study.44,45,46 The present study was conducted between April 15, 2018 and July 15, 2019 in a university hospital's pregnancy outpatient clinic. The trial protocol was registered (NCT04355091). Participants The current study's sample size was calculated using the G*Power application (Version 3.1.9.3). The sample size was calculated using a Cohen's standard effect size value of Results The current study concluded with 136 pregnant women, 69 in the intervention group and 67 in the control group. The consort flowchart of the study is shown in Fig. 2. Discussion The present study, which is the first randomized controlled study to evaluate the effectiveness of EFT on PPD, examined pregnant women's risk of depression and approaches to coping with anxiety and stress. However, because there are no studies in the literature on the effects of EFT on postpartum depression, this study's findings were discussed in reference to studies that evaluated the effectiveness of other psychotherapies on postpartum depression. In the current study, both the intervention Conclusion and recommendations The present study is the first to test the effectiveness of EFT applied during pregnancy on postpartum depression and shows that EFT reduce anxiety and depression, with long-term positive effects. The study findings reveal that EFT effectively reduce depression and anxiety and increases active (positive) coping styles. The study fndings confirm all the hypotheses generated at the beginning of the study. In the presence of mild depression, the study's findings support activating the therapeutic First page preview

Gueli, A., et al. (2019). "Laparoscopy vs. laparotomy for advanced ovarian cancer: a systematic review of the literature." Minerva Medica 110(4): 341-357.
	Introduction: In the last decade, laparoscopy has been progressively introduced in the management of advanced-stage ovarian cancer (AOC) to evaluate tumor resectability, avoiding an explorative laparotomy, to identify non-responders to submit to second-line chemotherapy and to perform primary or interval minimally invasive debulking surgery in selected patients. This review aims to deeply focus on the differences between laparoscopy and laparotomy in the management of advanced ovarian cancer.; Evidence Acquisition: The electronic database search provided a total of 80 results. Out of these, 63 results were excluded because considered not relevant to the review, for linguistic reasons or case reports. A total of 17 articles were considered eligible for the review.; Evidence Synthesis: Many studies have assessed the value of laparoscopy in predicting the optimal resectability of AOC patients avoiding exploratory laparotomies. More recently, its role in primary and interval cytoreduction has been investigated for selected patients in terms of safety, feasibility and oncological outcomes. Published data are comparable to the standard laparotomic management in terms of oncological outcomes but with improved perioperative and psychological results. The selection of patients is crucial to perform a successful surgery.; Conclusions: To date, laparoscopy has replaced the primary laparotomic approach in the evaluation of optimal resectability. As far as primary and interval minimally invasive debulking surgery are concerned, instead, most of the works report an overlap of oncological outcomes compared to traditional surgery. The selection of patients is a crucial point to reach a successful minimally invasive surgical treatment, taking into account surgical complexity and surgical adequacy.

Guerette, N., et al. (2022). "HIGH INTENSITY FOCUSED ELECTROMAGNETIC THERAPY VS. PELVIC FLOOR THERAPY WITH BIOFEEDBACK FOR TREATMENT OF FEMALE URINARY INCONTINENCE. A MULTI-CENTER RANDOMIZED-CONTROLLED TRIAL: 12-MONTH ANALYSIS." Female Pelvic Medicine & Reconstructive Surgery 28(6): S74.
	Introduction: The pelvic floor musculature (PFM) is essential for support and function of the pelvic organs. A common consequence of loss of PFM function is urinary incontinence (UI). Pelvic floor therapy (PFT), in particular biofeedback therapy, is a cornerstone of conservative management of urinary incontinence. However, studies of long‐term outcomes have had limited success and long‐term adherence has been challenging. This study investigated the efficacy of novel method of pelvic floor therapy, High Intensity Focused Electromagnetic Therapy (HIFEM), compared to conventional PFT with biofeedback for improvement of UI in women. Objective: The objective of the study was to compare HIFEM pelvic floor therapy to PFT with biofeedback for the treatment of UI as well as urinary urgency and frequency symptoms. Methods: Forty‐seven women (27‐66 years) at 3 centers diagnosed with UI were randomized to 2 groups: PFT (N = 22) and HIFEM (N = 25). All subjects underwent 6 treatment sessions scheduled twice a week for three weeks with either standard HIFEM therapy or a standardized pelvic floor biofeedback and electrical stimulation protocol adopted from Harvard Deaconess Department of Physical Therapy. Follow‐up visits performed at 1, 3, 6, 9 and 12 months after final treatment session. Outcome measures include qol questionnaires (ICIQBD, ICIQ‐LUTS), pad use, subjective leakage, therapy adherence, and therapy comfort. Adverse events and side effects were recorded. Results: Analysis at 6‐months post‐treatment showed significant improvement in UI symptoms measured by ICIQ‐LUTS in the HIFEM group (‐15.2 points, 35%, P < 0.001) but not in the PFT group (‐5.1 points, 13%, P = 0.24). Significant improvement over baseline was maintained at 12‐months in HIFEM (24%, P = 0.02) but not in the PFT group (3%, P = 0.85). ICIQ‐BD demonstrated greater improvement in urgency symptoms in the HIFEM vs. PFMT group (34% vs. 5%) at 12‐months. 87% of HIFEM subjects reported less leakage at 12‐months compared to 71% of PFMT subjects. Pad use decreased by ‐2.0/day in the HIFEM group vs. ‐0.4/day in the PFMT group. Average therapy comfort was rated 3.9/5 for HIFEM vs. 2.4/5 for PFMT at 12‐months. Subjects were 3.5 times more likely to complete the entire series of treatments in the HIFEM group. No adverse events or negative side effects were reported in either group. Conclusions: HIFEM technology appears safe and effective for the treatment of UI in women. HIFEM was more effective and better tolerated for the treatment of UI than conventional PFTwith biofeedback at 12‐months in this study. Larger studies are needed.

Guerin, J., et al. (2021). "Use of Hormonal Contraceptives in Perimenopause: A Systematic Review." Pharmacotherapy.
	INTRODUCTION: Hormonal contraceptives have been used in perimenopausal women to manage a variety of symptoms and prevent unintended pregnancy. However, it is unclear what contraceptive regimen is best for these women. OBJECTIVE: To evaluate hormonal contraceptive methods in women experiencing perimenopause using two prespecified outcomes: perimenopausal symptom management and long-term effects. METHODS: A literature search of PubMed and EMBASE databases was performed (January 1990 to October 2021) using search terms "perimenopause" and "contraception." Relevant full-text articles in English were included. RESULTS: Fifteen clinical articles were reviewed. Fourteen were internationally-based and one study was conducted in the United States. Nine articles evaluated symptom resolution, and six of these nine reported statistically significant changes in favor of treating perimenopausal women with hormonal contraceptives compared with no treatment. Seven studies evaluated long-term outcomes including bone loss and metabolic parameters, and six of these seven showed statistically significant improvements with hormonal contraceptives. Based on limited data and a lack of comparative studies, the use of a levonorgestrel intrauterine device with supplemental low-dose menopausal estrogen has positive results for the management of disruptive perimenopausal symptoms and long-term outcomes. CONCLUSION: Hormonal contraception in perimenopausal women improves symptom management and long-term outcomes if patients do not have contraindications. When selecting a contraceptive for women in perimenopause, clinicians and pharmacists need to address specific patient risk factors, symptom profiles, long-term risks and benefits, and patient preferences.

Guerra-Martin, M. D. and I. Guillen-Gallego (2020). "Effectiveness of the use of mindfulness in pregnancy, delivery and postpartum." Matronas Profesion 21(3-4): 59-66.
	Objective: To analyze the effectiveness of the mindfulness use in pregnancy, delivery and postpartum, and describe the different mindfulness methods. Methodology: A bibliographic review was carried out according to the objective of studies published between 2014-2019, in the databases: PubMed, CINAHL, WOS and Scopus, in the period March-April 2019. Result(s): A total of 124 studies were located and 22 were finally selected. Of these, 54.5% used mindfulness based on cognitive therapies (MBCT). 50% of the studies show effectiveness of the use of mindfulness, in terms of decreased anxiety and depression; however, in 13.6% they report that these aspects do not improve. Conclusion(s): There is scientific evidence of the use of mindfulness, with MBCT being the most widely used therapy. The use of mindfulness improves, among others, anxiety, depression, fear of childbirth, stress, nausea and vomiting.Copyright © 2021 Ediciones Mayo, S.A. All rights reserved.

Guerzoni, S., et al. (2023). "Monoclonal anti-CGRP antibodies in post-menopausal women: a real-life study." Acta neurologica Belgica 123(3): 1039-1047.
	Introduction: Migraine usually ameliorates after menopause. However, 10-29% of women still experience migraine attacks after menopause, especially if menopause is surgical. The use of monoclonal antibodies against the calcitonin gene-related peptide (CGRP) is changing the landscape of migraine treatment. This study aims to explore the effectiveness and safety of anti-CGRP monoclonal antibodies in women in menopause.; Methods: Women affected by either migraine or chronic migraine and treated with an anti-CGRP monoclonal antibody for up to 1 year. Visits were scheduled every 3 months.; Results: Women in menopause displayed a similar response compared to women of childbearing age. Among women in menopause, the women experiencing surgical menopause seemed to exhibit a similar response compared to the ones experiencing physiological menopause. Erenumab and galcanezumab displayed similar effectiveness in women in menopause. No serious adverse events were registered.; Discussion: The effectiveness of anti-CGRP monoclonal antibodies is almost the same between women in menopause and women of childbearing age, without appreciable differences between the different antibodies. (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Guha, P., et al. (2023). "Estrogen receptors as potential therapeutic target in endometrial cancer." Journal of receptor and signal transduction research 43(1): 19-26.
	Endometrial cancer (EC) is one of the most common gynecological carcinomas in both developed and developing countries. Majority of the gynecological malignancies are hormonally driven where estrogen signaling acts as an oncogenic signal. Estrogen's effects are mediated via classical nuclear estrogen receptors; estrogen receptor alpha and beta (ERα and ERβ) and a trans-membrane G protein-coupled estrogen receptor (GPR30 and GPER). ERs and GPER through ligand binding triggers multiple downstream signaling pathways causing cell cycle regulation, cell differentiation, migration, and apoptosis in various tissues including endometrium. Although the molecular aspect of estrogen function in ER-mediated signaling is now partly understood, the same is not true for GPER-mediated signaling in endometrial malignancies. Understanding the physiological roles of ERα and GPER in EC biology therefore leads to the identification of some novel therapeutic targets. Here we review the effect of estrogen signaling through ERα-and GPER in EC, major types, and some affordable treatment approaches for endometrial tumor patients which has interesting implications in understanding uterine cancer progression.

Gui, J., et al. (2019). "Impact of local endometrial injury on in vitro fertilization/intracytoplasmic sperm injection outcomes: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 45(1): 57-68.
	Aim: Recent studies have revealed positive effects of endometrial injury on clinical pregnancy rates, but with inconsistent results. The aim of this meta-analysis was to assess the efficacy of endometrial injury (biopsy and/or hysteroscopy) as a potential treatment measure for implantation failure in the in vitro fertilization population.; Methods: We searched in PubMed for studies comparing the efficacy of endometrial injury versus no intervention in women with at least one implantation failure. A random-effects model was used to evaluate the clinical pregnancy rate (CPR) and the live birth rate (LBR).; Results: Seventeen studies (11 randomized and 6 non-randomized studies) were included in this meta-analysis, including 1864 women in the intervention group and 2193 women in the control group. Overall, the CPR and LBR were significantly higher in the intervention group than in the control group (for CPR, n = 3997, 16 studies, P < 0.00001, risk ratio (RR) = 1.47, 95% confidence interval [CI] [1.24, 1.74]; for LBR, n = 2361, 11 studies, P = 0.003, RR = 1.41, 95% CI [1.12, 1.78]). However, after excluding the non-randomized studies, there was no significant difference in CPR (P = 0.29 for endometrial biopsy, P = 0.05 for hysteroscopy) and LBR (P = 0.23 for endometrial biopsy, P = 0.39 for hysteroscopy) between the intervention group and the control group.; Conclusion: There is still insufficient evidence to support the use of endometrial injury in women with implantation failure. Robust randomized controlled studies should be designed and performed before clinical implementation of endometrial injury. (© 2018 Japan Society of Obstetrics and Gynecology.)

Guida, F., et al. (2022). "Role of tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: Systematic review and meta-analysis." Gynecologic Oncology 166(1): 181-187.
	Objective: To evaluate the clinical utility of tertiary cytoreductive surgery (TCS) in recurrent ovarian cancer.; Methods: MEDLINE via PubMed, Embase (Elsevier), ClinicalTrials.gov, Scopus (Elsevier) and Web of Science for studies from inception to 4/09/2021. Studies reporting disease specific survival (DSS) and overall survival (OS) among women who underwent optimal cytoreductive surgery as compared to those who had a suboptimal cytoreductive surgery at time of TCS were abstracted. Study quality was assessed with the Quality In Prognosis Studies (QUIPS) tool. The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between survival and surgical outcomes.; Results: 10 studies met all the criteria for inclusion in the systematic review. Patients with optimal tertiary cytoreductive surgery had better DSS (HR = 0.35; 95% CI, 0.19-0.64, P < 0.001), with low heterogeneity (I 2 = 0%, P = 0.41) when compared to those with suboptimal tertiary cytoreductive surgery. Pooled results from these studies also demonstrated a better OS (HR = 0.34; 95% CI, 0.15-0.74, P < 0.007) with moderate heterogeneity (I 2 = 59%, P = 0.09) when compared to patients with a suboptimal tertiary cytoreductive surgery. This remained significant in a series of sensitivity analyses. Due to the limited number of studies, we were unable to do further subgroup analyses looking at outcomes comparing tertiary cytoreductive surgery to chemotherapy.; Conclusion: In this systematic review and meta-analysis of observational studies examining tertiary cytoreductive surgery for recurrent ovarian cancer, optimal tertiary cytoreductive surgery was associated with improved OS and DSS survival compared to suboptimal tertiary cytoreductive surgery. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Guidi, S., et al. (2021). "Adult Granulosa Cell Tumor in Pregnancy: A New Case and a Review of the Literature." Healthcare (Basel, Switzerland) 9(11).
	Granulosa cell tumors are rare ovarian tumors that can arise during pregnancy. We present a new case of recurrent adult granulosa cell tumor (AGCT) in pregnancy and a systematic review of the literature. The new case described is a 41-year-old woman G5P1122 with a prior history of AGCT that was referred to our center at 29 weeks because of a symptomatic abdominal mass, compatible with a possible recurrence of AGCT. At 36 + 3 weeks, she underwent a cesarean delivery for preterm labor and a total hysterectomy with a radical surgical staging. A healthy female infant was delivered. The patient received a platinum-based chemotherapy, with a 26-month follow-up negative for recurrence. Analyzing our case with the four identified by the literature review, three were recurrent and two were primary AGCT. Only one required surgery for AGCT at 15 weeks, while another underwent chemotherapy in pregnancy. In the other three cases, surgery for AGCT was done at the time of cesarean delivery. There were three cases of preterm delivery. All five pregnancies resulted in the birth of live babies with weight adequate for gestational age. In conclusion, AGCT diagnosed in pregnancy is rare, reported in only five cases. All gave birth to live babies in the third trimester, and maternal outcome at up to 18 months showed no recurrence.

Guild, D. J., et al. (2021). "Attachment and Affect between Mothers with Depression and their Children: longitudinal Outcomes of Child Parent Psychotherapy." Research on child and adolescent psychopathology 49(5): 563‐577.
	The present investigation examined the longitudinal effects of Child‐Parent Psychotherapy (CPP) for toddlers and their mothers with depression on: a) maternal affective expression, b) child affective expression, and c) mother‐child cohesion. Mothers with depression (Mage = 31.7 years; 92.8% White, 3.5% Black, 2.1% Hispanic, 2.3% other) and their toddlers were randomized to receive CPP (DI; n = 66) or to a control group (DC; n = 64). Mothers without depression and their toddlers (NC; n = 68) were recruited as an additional comparison group. Dyads were assessed at baseline (T1; 20 months old), post‐intervention (T2; 36 months old), and follow‐up (T3; 9 years old). Data from a mother‐child conflict task was coded as a measure of observed outcome variables. Change in post‐intervention attachment security assessed via the Strange Situation was evaluated as a mediator between intervention condition and maternal and child affective expression and dyadic cohesion at T3. Change to secure attachment post‐intervention significantly mediated the association between intervention condition and T3 maternal warmth and child anger/problem behavior. Toddlers of mothers with depression who received CPP showed higher rates of change to secure attachment compared to those in both the DC and NC groups. Dyads who changed to secure attachment at T2 displayed higher levels of maternal warmth at T3 and lower levels of child anger and problem behavior at T3. Implications for the use of CPP as a preventive intervention and the importance of attachment as a mediator of long‐term outcomes are discussed.

Guillon, S., et al. (2019). "A systematic review and meta-analysis of prognostic factors for remission in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 146(3): 277-288.
	Background: Endometrial cancer and atypical hyperplasia are rare in young women but create a dilemma between desire for pregnancy and oncologic outcomes.; Objective: To identify remission rates and associated prognostic factors in patients undergoing fertility-sparing management for endometrial cancer and atypical hyperplasia.; Search Strategy: MEDLINE was searched for studies published between January 1, 1950 and July 31, 2017 using various search terms.; Selection Criteria: Studies evaluating fertility-sparing management in patients aged between 19 and 44 years with atypical hyperplasia or stage I endometrial cancer.; Data Collection and Analysis: Use of PRISMA guidelines to conduct a meta-analysis of the proportion of patients in remission and meta-regression analysis to test the effect of possible prognostic factors for remission.; Main Results: A total of 3673 studies were screened; 65 studies including 1604 patients met the inclusion criteria. The remission rate was 0.75 (95% CI, 0.73-0.77). Operative hysteroscopy for endometrial sampling was associated with higher remission rates (OR 2.31; 95% CI, 1.10-4.84; P=0.03). Studies with higher ratios of infertile women were associated with higher remission rates (OR 4.21; 95% CI, 1.44-12.33; P<0.01).; Conclusion: Operative hysteroscopy is the preferred endometrial sampling method for patients with atypical hyperplasia or endometrial cancer undergoing fertility-sparing management. (© 2019 International Federation of Gynecology and Obstetrics.)

Guirguis, H., et al. (2023). "The impact of postinjection urinary tract infection on efficacy of intravesical onabotulinumtoxinA-A secondary analysis." Neurourology and Urodynamics 42(6): 1238-1244.
	Objectives: To compare treatment response in women who did and did not develop a urinary tract infection (UTI) within 14 days after intravesical onabotulinumtoxinA injections for treatment of refractory urgency urinary incontinence (UUI). Method(s): This is a secondary analysis of women who received Onabotulinumtoxin A in the Refractory Overactive Bladder: Sacral Neuromodulation vs Botulinum Toxin Assessment (ROSETTA) Trial. Participants were grouped by presence or absence of UTI within 14 days of injection. UTI was defined as symptomatic with positive urine culture per the primary ROSETTA protocol. Our primary outcome was change from baseline in mean number of UUI episodes based on monthly 3-day bladder diaries averaged over 6 months. We performed t tests and chi-square/Fisher's exact for continuous and categorical variables. A p value of <0.05 was considered statistically significant. Result(s): Of 187 participants in the onabotulinumtoxinA arm, 10 (5.3%) experienced UTI within 14 days of injection, and 177 (94.7%) did not. At baseline, groups did not differ in demographics, mean UUI episodes per day (no UTI [5.37 +/- 2.65] vs. UTI [6.40 +/- 3.02], p = 0.24), or other diary parameters. For our primary outcome, groups did not differ in the change in mean daily UUI episodes at 1 month (no UTI [-4.29 +/- 2.75] vs. UTI [-3.74 +/- 2.01]; mean difference [95% confidence interval, CI] -0.55 [-2.39 to 1.28], p: 0.55) or 6 months (no UTI [-3.63 +/- 2.89] vs. UTI [-2.15 +/- 3.18]; mean difference [95% CI] -1.48 [-3.44 to 0.48], p: 0.14). Conclusion(s): UTI within 14 days after intravesical injection of onabotulinumtoxinA for refractory UUI was not significantly associated with inferior treatment response at 1 or 6 months.Copyright © 2023 Wiley Periodicals LLC.

Guittard, C., et al. (2024). "Effect of tactile and/or kinesthetic stimulation therapy of preterm infants on their parents' anxiety and depressive symptoms: A systematic review." BMC Psychology 12(1): 3.
	Background: In the case of preterm birth, the idealized postnatal period is replaced by an anxious and even traumatic experience for parents. Higher prevalence of parental anxiety, postnatal depression, and posttraumatic stress disorder has been observed in mothers of preterm infants up to 18 months after childbirth. There is increasing evidence that proprioceptive stimulation has a beneficial effect on preterms' short-term outcomes. Could this care also have an impact on parental anxiety and depressive symptoms? We reviewed recent publications on the impact on parents' anxiety and depressive symptoms of delivering tactile and/or kinesthetic stimulation to their premature newborn.; Methods: We conducted a systematic review by searching the PubMed, PsycInfo, Scopus, ScienceDirect and Google Scholar databases for English-language publications from the past 10 years. We focused on the mothers or fathers of infants born preterm (before 37 weeks of gestation) who provided tactile and/or kinesthetic stimulation to their premature newborn in the neonatal intensive care unit. Relevant outcomes were the parents' anxiety, stress, depressive symptoms, and symptoms of posttraumatic stress disorder, assessed with reliable standardized inventories.; Results: Eleven articles were included in the systematic review. Results suggested a beneficial effect of parents' early tactile and kinesthetic stimulation of their preterm infants.; Conclusions: These interventions may act as protective factors against the occurrence of anxiety and depressive symptoms in parents and deserve to be studied further in this population. (© 2024. The Author(s).)

Gulati, G. and T. S. Bhagat (2022). "EFFECT OF CERVICAL MUCUS ASPIRATION ON PREGNANCY RATE IN INTRAUTERINE INSEMINATION." Journal of Pharmaceutical Negative Results 13: 802-805.
	Infertility1is a disease or disability that is both a health problem as well as a social problem. The problem of infertility has risen to enormous extent over the last few decades2which is attributable mainly to lifestyle changes, late age at marriage with growing women empowerment and increased incidence of pelvic infections. The prevalence of infertility varies widely, being less in developed countries and more in developing countries where limited resources for investigation and treatment are available3. It affects 60-80 million couples worldwide every year4. The prevalence of infertility in India ranges from 5-15%5. Infertility is classified as primary when the couple has not conceived even once or secondary when the couple has conceived at least once but is unable to conceive again. Secondary infertility occurs more commonly than primary infertility. The main causative factors for infertility are classified as female factors, male factors, combined male and female factors & unexplained infertility6. The cause of infertility is unexplained in 10-15 % of the cases5. The first step in treating infertility is to treat the underlying cause of infertility. The treatment modalities for infertility are broadly classified into three major categories medical treatment, surgical treatment and artificial insemination and different assisted reproductive technologies (ART) 7. The methods of insemination can be intravaginal, intracervical, intrauterine or intrafallopian. Intrauterine insemination (IUI) is a much cheaper, simpler & less invasive than more sophisticated assisted reproductive techniques. Intra Uterine Insemination is the most widely used medically assisted conception (MAC)technique.IUI is mainly indicated in patients with mild male factor, cervical mucus hostility, and idiopathic infertility. The pregnancy rate per IUI cycle varies between 6-22%8. The outcome of IUI may be affected by numerous factors such as timing9, number of inseminations (single or double)10, catheter type11, volume of prepared semen12and to some extent on the modality of ovulation induction. The rationale for the use of intrauterine insemination instead of intravaginal or intracervical insemination is to deposit the prepared semen as close as possible to the oocytes at the time of ovulation and also to bypass the effect of vaginal acidity and cervical mucus hostility. Intrauterine insemination is a better insemination technique as compared to other insemination methods because it bypasses the hostile cervical mucus. Therefore one way to increase pregnancy rate following IUI and perhaps during IVF13is to aspirate the cervical mucus before insemination. This study was conducted with the aim to evaluate the effect of cervical mucus aspiration on the pregnancy rate in intrauterine insemination.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Güler, B. and S. Mete (2023). "Effects of Relaxation-Focused Nursing Program in Women with Ovarian Cancer: A Randomized Controlled Trial." Pain management nursing : official journal of the American Society of Pain Management Nurses 24(4): e35-e45.
	Background: Surgical treatment is a major cause of hospitalization in ovarian cancer. In this process, physical problems, such as pain and changes in respiratory functions, and psychological problems, such as anxiety and stress, may develop.; Aim: This study aims to investigate the effects of the Relaxation-Focused Nursing Program on pain, anxiety, lung volume, level of knowledge, and nursing care satisfaction in ovarian cancer surgery.; Method: A randomized controlled trial in which participants were randomly assigned to either the experimental (preoperative relaxation exercises and education; n = 24) or control (usual nursing care; n =22) groups. The intervention consisted of practicing four sessions of relaxation exercises and education in the hospital for two days before surgery. Data were collected using the Trait and State Anxiety Inventory, Surgical Information Form, and Perioperative Assessment Form. The results were analyzed using the Friedman and Wilcoxon tests.; Results: The findings showed significant reductions in pain (p = .045) and anxiety scores (p < .001). The level of knowledge means scores were higher in the experimental group, but there was no significant difference between mean scores of spirometer volume and care satisfaction.; Conclusions: The program was more effective than usual nursing care in preoperative anxiety, pain, and level of knowledge. Although there was no difference between the care satisfaction scores of the patients, the reasons for care satisfaction were different in the program. Developing and implementing care that combines stress reduction interventions and preoperative education can improve the preoperative outcomes of patients.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Gulia, S., et al. (2023). "Secondary cytoreduction in platinum sensitive relapsed ovarian cancer: an individual patient level meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(9): 1440-1447.
	Objective: To synthesize the role of secondary cytoreduction in recurrent ovarian cancer from the results of randomized studies.; Methods: We conducted a meta-analysis of randomized controlled trials which compared secondary cytoreductive surgery versus no surgery in patients with platinum sensitive relapsed ovarian cancer. Individual patient data for overall survival and progression free survival were manually extracted from published survival curves, for whole study populations and subgroups based on completeness of surgical resection and bevacizumab use, using WebPlotDigitizer software. Overall survival and progression free survival curves for each study and the combined population were reconstructed from extracted data.; Results: Three studies with 1249 patients were included, of whom complete resection was achieved in 427 (34.2%) patients. In individual patient data analysis of the whole study population with 562 deaths, there was no significant difference in overall survival between the surgery and no surgery groups (median 52.8 vs 52.1 months, respectively, hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.80 to 1.11; p=0.5) but the surgery group had significantly longer progression free survival compared with the no surgery group (median 18.3 vs 14.4 months, respectively, HR 0.70, 95% CI 0.62 to 0.80; p<0.001). In subgroup analyses, overall survival was significantly longer in the complete cytoreduction subgroup compared with the no surgery group (median 62.0 vs 52.1 months, respectively, HR 0.70, 95% CI 0.57 to 0.92; p<0.001) while overall survival was significantly worse in the incomplete cytoreduction subgroup compared with the no surgery group (median 34.2 vs 52.1 months, respectively, HR 1.72, 95% CI 1.38 to 2.14; p<0.001). In the no bevacizumab subgroup, there was no significant overall survival difference between the surgery and no surgery groups (median 49.3 vs 47.0 months, HR 0.86, 95% CI 0.67 to 1.10; p=0.25).; Conclusions: Secondary cytoreductive surgery among women with platinum-sensitive relapsed ovarian cancer did not lead to significant benefit in overall survival although it increased progression free survival. However, overall survival was significantly longer among patients in whom complete cytoreduction was possible compared with no surgery.; Competing Interests: Competing interests: SGul: institutional financial interest for conducted research from Eli Lilly, Pfizer, Celltrion, Kendle India, and Zydus; non-remunerated activities include advisory board of Novartis and Eisai. SR: institutional financial interest for conducted research from AstraZeneca and JSS Clinical Research. SGup: institutional financial interest for conducted research from Roche, Sanofi, Johnson & Johnson, Amgen, Celltrion, Oncosten, Novartis, Intas, Eisai, Biocon, and AstraZeneca; non-remunerated activities include advisory board of Sanofi, Dr Reddy’s Laboratories, Biocon, Pfizer, Oncosten, Core Diagnostics, and AstraZeneca; general secretary of non-profit organization, Women Cancer Initiative and president-elect of the Indian Society of Medical and Pediatric Oncology. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Gulino Ferdinando, A., et al. (2022). "Anti-Mullerian Hormone (AMH) and adenomyosis: Mini-review of literature of the last 5 years." Frontiers in Endocrinology 13: 1014519.
	Introduction: Adenomyosis is a form of endometriosis characterized by the presence of endometrial tissue in the myometrium. The correlation between anti-Mullerian hormone (AMH) expression and adenomyosis is unclear. Few studies investigated this possible correlation with promising results. The aim of this mini-review is to illustrate the potential prognostic and therapeutic role of AMH in adenomyosis.; Materials and Methods: A study protocol was completed conforming to the Preferred Reporting Items for Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We performed an electronic databases search from each database's inception from August 2017 to August 2022 for full-text articles and published abstracts. For database searches, the following main keywords were the following text words: "adenomyosis" or "uterine endometriosis" [Mesh] AND "AMH" or "anti-mullerian hormone".; Results: From the literature search, 8 abstracts of studies were retrieved and independently screened for inclusion by three authors. It was found that the most common therapeutic strategies (such as adenomyomectomy and high-intensity focused ultrasound (HIFU) do not alter AMH levels. Moreover, a higher expression of the AMH receptor II was observed in adenomyotic tissue, hence a possible therapeutic use of AMH was hypothesized.; Conclusion: The available evidence shows an unclear relationship between adenomyosis and AMH. Probably, women with adenomyosis have lower levels of AMH and the surgical treatment (adenomyomectomy, HIFU) does not alter this characteristic, therefore in all of them, ovarian function is not influenced.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Gulino, Dilisi, Capriglione, Cannone, Catania, Martire, Tuscano, Gulisano, D’Urso, Di Stefano, Cimino, Filippini, Latella, Sammarini, Musmeci and Palumbo.)

Gullo, G., et al. (2022). "Ovarian tissue cryopreservation and transplantation in menopause: new perspective of therapy in postmenopausal women and the importance of ethical and legal frameworks." European Review for Medical and Pharmacological Sciences 26(24): 9107-9116.
	Menopausal transition entails a progressive decrease in hormone production by the ovaries that lead to important physical and psychological changes that could significantly affect quality of life. Hormone replacement therapy (HRT) administered from the onset of menopausal symptoms usually improves quality of life and life expectancy. Nevertheless, it is not risk-free. Ovarian tissue cryopreservation (OTC) has been investigated as a potential new strategy for delaying menopause and/or to avoid HRT. This review analyzes the critical points of HRT to assess whether OTC and subsequent reimplantation can affect postmenopausal management. We assessed available randomized clinical trials in PubMed, Cochrane Library, ISI web of science, and Scopus from August 2021 to November 2022, including studies and trials evaluating the efficacy of OTC in both cancer and menopausal patients, the efficacy of freezing techniques and the possible clinical scenarios that OTC can open, even from the standpoint of legal and ethical issues arising as such innovative techniques become mainstream. Lower duration of the graft and efficacy on estrogen secretions at a physiological and safer concentration of estrogen than conventional HRT based on hormonal supplements. OTC can reportedly trigger estrogen secretions at a lower and safer physiological concentration than conventional HRT. OTC and subsequent reimplantation remain a valid fertility-sparing approach in patients undergoing gonadotoxic treatments. Further studies are needed to better evaluate its safety and efficacy within postmenopausal therapy management and in order to lay out widely shared and evidence-based guidelines and best practices and perform such novel and innovative techniques in a legally and ethically safe fashion, in the best interest of patients and healthcare professionals.

gunagpeng, w. and l. xueyan (2021). "Telemedicine treatment of postpartum depression: a systematic review."
	
Gundogdu, E. C. and T. G. Yilmaz (2023). "The role of intraoperative superior hypogastric plexus blocks in pain management for total abdominal hysterectomy: a comparative study." European Research Journal 9(5): 1201-1206.
	Objectives: This study aimed to investigate the efficacy of intraoperative Superior Hypogastric Plexus Blocks (SHPBs) in managing postoperative pain following total abdominal hysterectomy, comparing pain scores and analgesic requirements between patients who received SHPBs and those who did not. Method(s): A prospective, randomized, controlled trial was conducted on 70 female patients undergoing elective total abdominal hysterectomy. Patients were randomly assigned to either the SHPB group or the non-SHPB group. In the SHPB group, intraoperative SHPBs were administered after uterine removal. Postoperative pain scores were assessed using the Visual Analogue Scale (VAS) at various time points. Analgesic consumption and adverse effects were also recorded. Result(s): Patients in the SHPB group consistently exhibited lower pain scores compared to the non-SHPB group at various postoperative time intervals (p < 0.05). Initial analgesic requirements were significantly higher in the non-SHPB group, as was total analgesic consumption during the hospital stay (p < 0.05). No significant complications related to SHPB administration were observed. Conclusion(s): Intraoperative Superior Hypogastric Plexus Blocks demonstrated a potential benefit in reducing postoperative pain scores and analgesic consumption in patients undergoing total abdominal hysterectomy. These findings highlight the potential of SHPBs as an effective approach to enhance pain management in this surgical population, warranting further investigation and refinement of administration protocols.Copyright © 2023 by Prusa Medical Publishing.

Gunduz-Bruce, H., et al. (2022). "Development of neuroactive steroids for the treatment of postpartum depression." Journal of neuroendocrinology 34(2): e13019.
	Postpartum depression (PPD) is a common major depressive episode surrounding childbirth, with estimated rates ranging from 5.5% to 23.5% of all live births across Europe and the USA based on the presence of key symptoms. PPD has been associated with significant impairments in both maternal functioning and mother-infant attachment, and these impairments can have lasting effects on the emotional and cognitive development of children. Although the precise pathophysiology of PPD is unknown, preclinical findings suggest that large fluctuations in neurosteroid hormone levels can induce physiological plasticity in the expression of functional GABA A receptors during pregnancy and the postpartum period, and that deficits in this plasticity may underpin a biological mechanism that contributes to the manifestation of depressive symptoms. Here, we review the controlled clinical trials to date that have assessed the efficacy of pharmacological treatments for PPD, including oestradiol, selective serotonin reuptake inhibitors, brexanolone (an iv formulation of allopregnanolone) and an investigational neuroactive steroid and GABA A positive allosteric modulator, zuranolone. Coupled with the GABAergic deficits implicated in major depressive disorder, these findings highlight not only the potential role of GABA A receptor plasticity in the pathophysiology of PPD, but also the novel therapeutic approach of using positive allosteric modulators targeting GABAergic transmission to treat women affected by PPD. (© 2021 Sage Therapeutics Inc. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Gungorduk, K., et al. (2021). "Robotic platforms for endometrial cancer treatment: Review of the literature." Minerva Medica 112(1): 47-54.
	INTRODUCTION: The cornerstone in the management of endometrial cancer (EC) is surgical staging. Over the last few decades, minimally invasive surgery has been widely accepted as a mainstay in the treatment of endometrial cancer. The first robotic-assisted gynecological surgery was performed in 1998. EVIDENCE ACQUISITION: The literature search was conducted using MEDLINE, EMBASE and PUBMED databases from January 1998 to September 2020. EVIDENCE SYNTHESIS: Several studies have reported the advantages of robotic-assisted surgery over laparoscopy in the management of EC. These are most pronounced in obese patients. Robotic-assisted surgery is also associated with a shorter learning curve, particularly for lymphadenectomy, which enables more surgeons to perform minimally invasive surgery for EC. CONCLUSION(S): The effectiveness and oncological results of robotic surgery for EC appear to be similar to those of other surgical methods, but fewer intraoperative complications occur than with other methods.Copyright © 2021 Edizioni Minerva Medica. All rights reserved.

Gungorduk, K. and A. Ozdemir Isa (2021). "Non-pharmacological interventions for the prevention of postoperative ileus after gynecologic cancer surgery." Taiwanese Journal of Obstetrics & Gynecology 60(1): 9-12.
	Postoperative ileus (POI) is characterized by impaired gastrointestinal motility after surgery. POI is a major concern for surgeons because it increases hospital stay, the cost of care, and postoperative morbidity in patients who have undergone extensive gynecological oncological surgery. Although several interventions have been proposed and investigated, no effective treatment for the prevention and management of POI has been established. The present review summarizes the current evidence on non-pharmacological interventions, including coffee consumption and chewing gum, used to prevent and treat POI. We obtained studies from MEDLINE, Cochrane Database of Systematic Reviews, ISI Web of Science, and SCOPUS databases.; Competing Interests: Declaration of competing interest The author has no conflicts of interest to disclose. (Copyright © 2021. Published by Elsevier B.V.)

Gungorduk, K., et al. (2024). "Effect of abdominal hot pack application on gastrointestinal motility recovery after comprehensive gynecologic staging surgery." International Journal of Gynecology and Obstetrics 164(3): 1108-1116.
	Objective: To evaluate whether abdominal hot water pack application improves gastrointestinal motility following gynecological oncology surgery. Method(s): The study was registered at ClinicalTrials.gov (NCT04833699). (https://clinicaltrials.gov/ct2/show/NCT04833699?cond=NCT04833699&draw=2&rank=1). In this randomized controlled trial, participants were randomly assigned (1:1) to the hot water pack group (standardized enhanced recovery protocols plus rubber water bag with a fluffy cover filled with boiled tap water [80degreeC] and placed on the abdomen at 3, 6, 9, and 12 h postoperatively for 30 min each time) or the control group (standardized enhanced recovery protocols). A subumbilical or supraumbilical vertical midline incision was made to perform staging surgery procedures, including hysterectomy, salpingo-oophorectomy with retroperitoneal lymphadenectomy. The primary outcome was the time to first passage of flatus from the end of the staging procedure. Result(s): In total, 121 women were randomized to the control (n = 62) or hot water pack (n = 59) group. The use of an abdominal hot water pack significantly reduced the mean time to passing first flatus (25.2 +/- 3.6 vs. 30.6 +/- 3.9 h; hazard ratio [HR] = 4.4; 95% confidence interval [CI]: 2.8-7.1; P < 0.0001), mean time to first bowel movements (28.4 +/- 4.0 vs. 34.4 +/- 4.5 h; HR = 4.9; 95% CI: 3.0-7.9; P < 0.0001), mean time to first defecation (33.4 +/- 4.9 vs. 41.0 +/- 7.6 h; HR = 4.3; 95% CI: 2.1-6.8; P < 0.0001), and mean time to tolerating solid diet (2.1 +/- 0.6 vs. 2.8 +/- 1.0 days; HR = 4.4; 95% CI: 2.2-8.7; P < 0.0001) compared to the control group. The postoperative ileus incidence was significantly lower in the hot water pack group (3.4%) than the control group (16.1%) (P = 0.01). Conclusion(s): Abdominal hot water pack application improved gastrointestinal function recovery in women following surgical staging procedures for gynecological malignancy.Copyright © 2023 International Federation of Gynecology and Obstetrics.

Gunter, J. (2024). "Fractional CO2 laser for genitourinary syndrome of menopause: evaluating the evidence." Menopause (New York, N.Y.) 31(3): 231-233.
	The fractionated CO2 laser has been marketed to women for a variety of gynecologic symptoms and conditions, including the genitourinary syndrome of menopause (GSM). The evidence has been limited, precluding conclusions regarding the efficacy and safety of the therapy. However, data from randomized, controlled trials evaluating this technology for GSM are now available. This Practice Pearl addresses the latest data concerning the use of the fractionated CO2 laser for the treatment of GSM. (Copyright © 2024 by The Menopause Society.)

Guo Emma, J., et al. (2019). "Reproductive outcomes after surgical treatment of asherman syndrome: A systematic review." Best practice & research. Clinical obstetrics & gynaecology 59: 98-114.
	In this systematic review, we analysed the reproductive outcomes of hysteroscopic adhesiolysis in women with Asherman syndrome (AS). We searched PubMed, Web of Science and Cochrane Library (from database inception to April 2018) and selected studies that quantitatively described the reproductive outcomes. We assessed study quality and pooled rate data for each outcome. There were 54 studies (4640 women) of varying quality. The pooled rate of pregnancy was 50.7% (95% CI [confidence interval]: 49.1 to 52.3) in 53 studies, early pregnancy loss was 17.7% (95% CI: 15.9 to 19.6) in 31 studies, ectopic pregnancy (EP) was 4.2% (95% CI: 2.8 to 6.3) in 9 studies, mid-trimester loss (MTL) was 11.5% (95% CI: 7.6 to 17.8) in 7 studies, cervical incompetence was 12.5% (95% CI: 3.3 to 33.5) in 2 studies and placenta accreta syndrome was 10.1% (95% CI: 8.6 to 11.8) in 23 studies. The pregnancy rate in women with severe adhesion was significantly lower than that in women with mild adhesion (P = 0.021). These results can be used to counsel women with AS before surgical treatment and for planning antenatal care after conception. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Guo, F. and H. Wang (2022). "Potential of histone deacetylase inhibitors for the therapy of ovarian cancer." Frontiers in Oncology 12: 1057186.
	Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemotherapy increase patient mortality. Accumulating evidence demonstrates that histone modifications play a key role in cancerization and progression. Histone deacetylases is associated with chromatin condensed structure and transcriptional repression and play a role in chromatin remodeling and epigenetics. Histone deacetylases are promising targets for therapeutic interventions intended to reverse aberrant epigenetic associated with cancer. Therefore, histone deacetylases inhibitors could be used as anti-cancer drugs. Preclinical studies have shown promising outcomes of histone deacetylases inhibitors in ovarian cancer while clinical trials have had mixed results and limited success as monotherapy. Therefore, combination therapy with different anticancer drugs for synergistic effects and newly selective histone deacetylases inhibitors development for lower toxicity are hot issues now. In this review, we summarize the latest studies on the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors as monotherapy or combination therapy in ovarian cancer.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Guo and Wang.)

Guo, H. and Q. Lu (2021). "Efficacy of dydrogesterone on treating recurrent miscarriage and its influence on immune factors: a systematic review and meta-analysis." Annals of Palliative Medicine 10(10): 10971-10985.
	Background: This study aimed to explore the clinical efficacy of dydrogesterone in treating recurrent spontaneous abortion (RSA), analyze the influence of dydrogesterone on cellular immune factors, and provide evidence for clinical medication.; Methods: We used the China National Knowledge Infrastructure (CNKI) platform, Wanfang Data resource, PubMed, Web of Science, and Embase database to conduct a literature search to screen clinical studies published between 2005 and 2021 concerning dydrogesterone treatment for RSA. Stata 16.0 was used for meta-analysis and sensitivity analysis, and Begg's funnel chart was used to test publication bias.; Results: Only 13 studies, which included a total of 2,454 RSA patients, met the study inclusion criteria. The experimental group was treated with dydrogesterone, and the control group was treated with progesterone, human chorionic gonadotropin (hCG), placebo, or active immunization. Meta-analysis showed that the pregnancy success rate of the experimental group was higher than the control group, and the adverse reaction rate was lower than the control group. In addition, subgroup analysis also revealed that the experimental group had a higher pregnancy success rate than the control group and a lower adverse reaction rate. Levels of progesterone and hCG in the experimental group were dramatically higher than the control group after treatment. The experimental group also had higher levels of interleukin 4 (IL-4) and interleukin 10 (IL-10) than the control group, while levels of interferon-gamma (IFN-γ) were lower.; Discussion: Dydrogesterone, a safe and effective synthetic progesterone drug, had a significant clinical effect on RSA and effectively improved hormone levels and related cellular immune factors in RSA patients.

Guo, J., et al. (2021). "Outcomes of Trachelectomy vs. Hysterectomy for Early-Stage Cervical Cancer: A Systematic Review and Meta-Analysis." Frontiers in surgery 8: 735944.
	Objective: To provide updated evidence on comparative efficacy for clinical outcomes of radical trachelectomy and radical hysterectomy in patients with early-stage cervical cancer. Methods: A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews, and Google scholar databases. Studies were done in patients with early-stage cervical cancer that compared the outcomes between radical trachelectomy (RT) and hysterectomy (RH) were considered for inclusion in the review. The outcomes of interest were operative time, the volume of blood loss, need for blood transfusion, any complications, length of hospital stay, risk of recurrence, and survival. The strength of association was presented in the form of pooled relative risk (RR), hazards risk (HR), and weighted mean difference (WMD). Statistical analysis was done using STATA version 16.0. Results: A total of 12 articles were included in the meta-analysis. The majority were retrospective cohort-based studies. Compared to RH, the operative time (in min) was comparatively higher in RT (WMD 23.43, 95% CI: 5.63, 41.24). Patients undergoing RT had blood loss (in ml) similar to those undergoing RT (WMD -81.34, 95% CI: -170.36, 7.68). There were no significant differences in the risk of intra-operative (RR 1.61, 95% CI: 0.49, 5.28) and post-operative complications (RR 1.13, 95% CI: 0.54, 2.40) between the two groups. Patients in the RT group had lesser duration of post-operative hospital stay (in days) (WMD -1.65, 95% CI: -3.22, -0.09). There was no statistically significant difference in the risk of recurrence (HR 1.21, 95% CI: 0.68, 2.18), 5-year overall survival (HR 1.00, 95% CI: 0.99, 1.02), and recurrence-free survival (HR 0.99, 95% CI: 0.96, 1.01) between the two groups. Conclusion: Among the patients with early-stage cervical cancer, RT is similar to RH in safety and clinical outcomes. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Guo, Hu, Deng and Jin.)

Guo, J., et al. (2023). "Comparison of the probability of four anticonvulsant mood stabilizers to facilitate polycystic ovary syndrome in women with epilepsies or bipolar disorder-A systematic review and meta-analysis." Frontiers in Psychiatry 14: 1128011.
	Background: Patients treated with anticonvulsant mood stabilizers have a higher incidence of polycystic ovary syndrome (PCOS). However, there is no comparison between different anticonvulsant mood stabilizers. The purpose of this study was to systematically evaluate the prevalence of PCOS in women taking anticonvulsant mood stabilizers and compare the probability of PCOS caused by different anticonvulsant mood stabilizers.; Methods: Five databases, namely PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials, were searched for literature on anticonvulsant mood stabilizers and PCOS published up to October 28, 2022. This meta-analysis was performed using Revman 5.4, Stata 14.0, and R4.1.0, and effect size pooling was performed in fixed- or random-effects models based on the results of I 2 and Q-test, and the surface under the cumulative ranking curve (SUCRA) was used for analysis to assess the cumulative probability of drug-induced PCOS. Publication bias was assessed by funnel plot Egger's test and meta regression.; Results: Twenty studies with a total of 1,524 patients were included in a single-arm analysis, which showed a combined effect size (95% CI) of 0.21 (0.15-0.28) for PCOS in patients taking anticonvulsant mood stabilizers. Nine controlled studies, including 500 patients taking medication and 457 healthy controls, were included in a meta-analysis, which showed OR = 3.23 and 95% CI = 2.19-4.76 for PCOS in women taking anticonvulsant mood stabilizers. Sixteen studies with a total of 1416 patients were included in a network meta-analysis involving four drugs, valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), and lamotrigine (LTG), and the results of the network meta-analysis showed that VPA (OR = 6.86, 95% CI = 2.92-24.07), CBZ (OR = 3.28, 95% CI = 0.99-12.64), OXC (OR = 4.30, 95% CI = 0.40-49.49), and LTG (OR = 1.99, 95% CI = 0.16-10.30), with cumulative probabilities ranked as VPA (90.1%), OXC (63.9%), CBZ (50.1%), and LTG (44.0%).; Conclusion: The incidence of PCOS was higher in female patients treated with anticonvulsant mood stabilizers than in the healthy population, with VPA having the highest likelihood of causing PCOS. The most recommended medication when considering PCOS factors is LTG.; Systematic Review Registration: identifier: CRD42022380927.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Guo, Liu, Kong, Sun, Lu, Lu, Qu and Yue.)

Guo Julia, Z., et al. (2020). "Vaginal laser treatment of genitourinary syndrome of menopause: does the evidence support the FDA safety communication?" Menopause (New York, N.Y.) 27(10): 1177-1184.
	Importance: Genitourinary syndrome of menopause (GSM) is a chronic, progressive condition frequently manifesting as vaginal dryness and pain with intercourse. Survey data indicate this is a highly prevalent, likely underreported, condition that profoundly affects quality of life for millions of women. Vaginal lasers demonstrate promise as an effective, nonhormone therapeutic alternative for GSM; however, the risks associated with them may have been overstated.; Objective: Despite reports of improved sexual and vaginal comfort without serious safety concerns, the Food and Drug Administration (FDA) issued a 2018 safety communication warning against it. We conducted a systematic literature review and surveyed both the FDA Manufacturer and User Facility Device Experience (MAUDE) and Bloomberg Law Databases to evaluate risks associated with laser treatment for GSM.; Evidence Review: A systematic literature review identified articles published before September 2019. The MAUDE database was searched by name from 2009 to 2019 for safety claims for 24 vaginal laser devices. The Bloomberg Law database was searched for product liability claims against any vaginal laser device manufacturer before July 2019.; Findings: Literature review revealed 3 publications detailing 29 presumptive laser-associated complications, only 5 of which (17.2%) reported worsening symptoms after treatment. The MAUDE database contained 120 complaints; only 30 (25%) detailed potential adverse patient events, most frequently pain (n = 12) and burning (n = 10). The Bloomberg law database contained no claims asserting harm from device use.; Conclusions and Relevance: Lacking strong evidence indicating significant patient risk for vaginal laser treatment of GSM, the FDA safety communication appears unsubstantiated and implies gender bias. Identified complications suggest most reported "adverse events" represent lack of treatment effect. The well-documented benefits and low risk of adverse event suggest laser therapy for GSM is reasonable with appropriate pretreatment counseling. Additional randomized, well-controlled clinical trials are needed to further elucidate both the safety and efficacy of this nonhormone therapy.

Guo, M., et al. (2022). "Metformin Use and Mortality in Women with Ovarian Cancer: An Updated Meta-Analysis." International Journal of Clinical Practice 2022: 9592969.
	Background: Previous observational studies and meta-analysis suggested a possible association between metformin use and reduced mortality in women with ovarian cancer (OC). However, clinical factors that may influence the relationship remain poorly evaluated. We performed an updated meta-analysis to systematically evaluate the above association and to observe the potential influences of study characteristics on the association.; Methods: Relevant studies reporting the association between metformin use and mortality in women with OC in the multivariate adjusted model were identified by search of electronic databases that included PubMed, Embase, and Web of Science. The random-effects model was adopted to combine the results.; Results: Nine studies including 10030 women with OC were included. Overall, metformin use was independently associated with reduced overall mortality (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55-0.93, P =0.01; I 2 = 62%). Consistent results were observed for studies comparing metformin users with nondiabetic women and studies comparing metformin users with diabetic women who did not use metformin ( P for subgroup analysis = 0.70). Further subgroup analyses showed consistent results in studies with metformin use before or after the diagnosis of OC, with or without adjustment of body mass index (BMI) and with or without adjustment of concurrent medications ( P for subgroup analyses all >0.10).; Conclusion: Metformin use is associated with reduced mortality in women with OC, which may be independent of the diabetic status of the controls, timing of metformin use, or adjustment of BMI and concurrent medications. Clinical trials are needed to validate the potential benefits of metformin on survival of OC.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Mingchuan Guo et al.)

Guo, Q., et al. (2022). "Comparison of adjuvant chemoradiotherapy versus radiotherapy in early-stage cervical cancer patients with intermediate-risk factors: A systematic review and meta-analysis." Taiwanese Journal of Obstetrics & Gynecology 61(1): 15-23.
	The presence of intermediate risk factors reduces the predictability of radical hysterectomy, demanding the use of adjuvant therapy for treatment of Early stage cervical cancer (ESCC) patients. Adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) has been widely used with varied efficacy and safety issues. Therefore, the aim of this systematic review and meta-analysis was to update the available evidence and assess the effect of post-surgical adjuvant RT versus adjuvant CRT on survival rate and complications/toxicities in management of ESCC patients with intermediate risk factors. PubMed, EMBASE and Web of Science (WOS) and CENTRAL were searched using a combination of relevant keywords. All studies comparing outcomes of adjuvant RT versus CRT in ESCC patients with intermediate-risk factors in terms of recurrence free survival (RFS), overall survival (OS) and toxicities/complications were included. Both qualitative and quantitative analysis was carried out. The risk of bias assessment was done using Newcastle-Ottawa scale (NOS) for retrospective cohort studies and Cochrane risk of bias assessment tool was used for randomized clinical trials. Eleven retrospective cohort studies and two randomized clinical trials were included in this review. Adjuvant CRT was found to have better RFS with ESCC patients with multiple intermediate risk factors with OR 3.11 95% CI [1.04, 4.99], p < 0.0001; i2 = 6%. However, similar benefit was observed between both regimens in presence of a single intermediate risk factor OR 1.80 95% CI [0.96, 3.36], p = 0.07; i2 = 0%. Grade 3 or 4 haematological toxicity among patients receiving post-surgical adjuvant RT versus adjuvant CRT showed increased association of toxicity with adjuvant CRT with OR 7.73 95%CI [3.40, 17.59], p < 0.0001; i2 = 62%. Adjuvant CRT shows favourable RFS and OS in ESCC patients with multiple intermediate risk factors. CRT also showed greater incidence of grade 3 or 4 haematological and non-haematiological toxicity, however, the same could be well tolerated when used within the recommended dosage. (Copyright © 2021. Published by Elsevier B.V.)

Guo, T., et al. (2019). "Identifying the superior surgical procedure for endometrial polypectomy: A network meta-analysis." International Journal of Surgery 62: 28-33.
	Objective: To identify the superior surgical procedure for endometrial polypectomy based on network meta-analysis.; Method: Literature retrieval was conducted in globally recognized databases, namely, MEDLINE, EMBASE and Cochrane Central, to address relative randomized controlled trials (RCTs) investigating the clinical effects of respective surgical procedure for endometrial polypectomy. Surgical parametric data, including operative time, success rates and complications, were quantitatively pooled and estimated based on the Bayesian theorem. The values of surface under the cumulative ranking (SUCRA) probabilities regarding each parameter were calculated and ranked by various procedures. Node-splitting analysis was performed to test the inconsistency of the main results and publication bias was assessed by examining funnel-plot symmetry.; Results: After a detailed review, 8 RCTs containing 5 different procedures were finally included for network meta-analysis. The results indicated that hysteroscopic morcellation possessed the highest possibility of revealing best clinical effects on operative time (SUCRA, 0.49), success rate (SUCRA, 0.90) and complications (SUCRA, 0.50). Moreover, node-splitting analysis and funnel-plot symmetries illustrated no inconsistency or obvious publication bias in the current study.; Conclusions: Current evidence demonstrated that hysteroscopic morcellation showed optimal potential superior clinical effects for endometrial polypectomy compared to other procedures. However, high-quality large sample trials are still expected, and new investigations on other relative procedures in this field should be included in the future. (Copyright © 2019. Published by Elsevier Ltd.)

Guo, W., et al. (2023). "Compare the Efficacy of Dienogest and the Levonorgestrel Intrauterine System in Women with Adenomyosis." Clinical therapeutics 45(10): 973-976.
	Purpose: The goal of this study was to examine the efficacy and safety of the levonorgestrel intrauterine system (LNG-IUS) versus dienogest (DNG) in female subjects with symptomatic uterine adenomyosis.; Methods: This study enrolled 117 women with symptomatic adenomyosis who visited our hospital from May 1, 2019, to June 30, 2022. Participants were randomized to either the LNG-IUS group (n = 48) or the DNG group (n = 79) in an as-controlled clinical trial for 36 months. Visual analog scale (VAS) scores, uterine volume, endometrial thickness, serum carcinoma antigen 125 level, estradiol, follicle-stimulating hormone, luteinizing hormone, and side effects were assessed to compare the efficacy of LNG-IUS and DNG.; Findings: The VAS pain score was significantly decreased in both groups after 3 months of treatment. Three months later, patients receiving DNG reported significantly lower VAS scores compared with those treated with LNG- IUS (P < 0.05). Compared with LNG-IUS, DNG effectively controlled uterine volume growth after 12 months of treatment but neither significantly reduced uterine volume. During the treatment period, endometrial thickness in both groups was maintained at 0.4 to 0.7 cm.; Implications: Both DNG and LNG-IUS significantly improved adenomyosis-associated pain after 3 months of treatment. Compared with LNG-IUS, DNG was shown to continuously relieve the symptoms of pain and effectively control the growth of uterine volume.; Competing Interests: Declaration of Competing Interest None declared. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Guo, X. L., et al. (2020). "Acupuncture for pain relief of women undergoing transvaginal oocyte retrieval: A meta analysis and systematic review protocol." Medicine (United States) 99(39): E22383.
	Background:Pain during oocyte retrieval, which can make the in-vitro fertilization process an unpleasant experience, is becoming a common problem. Although there are many analgesic methods available in the clinical setting, they are not therapeutically equivalent, and some are associated with varying adverse reactions. In recent years, acupuncture analgesia has been used in the perioperative period of oocyte retrieval because of its perceived efficacy and safety. The purpose of this systematic review and meta-Analysis is to provide evidence that acupuncture is effective in the treatment of vaginal oocyte retrieval pain. Method(s):Electronic searches of the following six databases will be conducted by two qualified reviewers: MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Medicine database, VIP database and Wanfang database. Three clinical trial registries will also be searched: World Health Organization International Clinical Trial Registry Platform, Chinese Clinical Trial Registry, Cochrane Central Register of Controlled Trials and ClinicalTrials.Gov. All searches will cover the period from inception of the database/registry to March 2020 and will be limited to publications in English and Chinese. Data identification, data selection, data extraction, and bias risk assessment will be conducted independently by3v two or more qualified reviewers, including those who selected the studies. Visual analogue scale scores will be calculated as the primary outcome. Secondary outcomes will include results of other subjective pain rating scales, including Likert scales or other defined numerical or non-numerical scales, self-Assessed by patients before, during, and after oocyte retrieval. We will use STATA software (Version 16) to perform meta-Analyses, and the Grading of Recommendations, Assessment, Development and Evaluations framework to grade the quality of evidence. If quantitative analysis is not available, a systematic narrative synthesis will be provided.PROSPERO registration number:CRD42020170095.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Guo, Y., et al. (2023). "Current research of assisted reproductive technology for women with early endometrial carcinoma and atypical endometrial hyperplasia after conservative treatment." Chinese Journal of Reproduction and Contraception 43(3): 311-315.
	In recent years, the incidence of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) has increased than before and showed a tendency to be younger. Meanwhile, young women diagnosed with EC or AEH have strong desires to preserve their fertilities, so that they may choose the conservative treatment. After achieving complete remission, many of them are recommended to undergo assisted reproductive technology (ART) treatment to conceive. At present, the research on ART after conservative treatment of EC and AEH is increasing year by year, but most of them are small sample studies. This article reviewed existing studies to explain the effectiveness, safety and influencing factors of ART after conservative treatment of EC and AEH.Copyright © 2023 Authors. All rights reserved.

Guo, Y.-J., et al. (2020). "Efficacy of transcranial magnetic stimulation and fluoxetine in the treatment of postpartum depression: A protocol for systematic review and meta-analysis." Medicine 99(21): e20170.
	Background: Numerous studies have reported that transcranial magnetic stimulation (TMS) and fluoxetine is used in the treatment of postpartum depression (PPD). Currently, no study has systematically investigated the efficacy and safety of TMS and fluoxetine for the treatment of patients with PPD. Thus, this study will assess the efficacy and safety of TMS and fluoxetine for treating PPD.; Methods: Relevant studies involving TMS and fluoxetine for the treatment of patients with PPD will be comprehensively searched from the electronic databases from inception to the February 1, 2020: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, WANGFANG, VIP, and CNKI databases. No language and publication time restrictions will be applied. RevMan 5.3 software will be utilized for data pooling, data analysis, and risk of bias evaluation. If necessary, we will also assess reporting bias using funnel plot and Egger test.; Results: This study will comprehensively summarize the existing evidence to assess the efficacy and safety of TMS and fluoxetine for treating PPD.; Conclusion: The findings of this study may help to establish a better approach to treat PPD using TMS and fluoxetine.; Dissemination and Ethics: This study will be disseminated through a peer-reviewed journal. This study does not need ethical approval as no primary patient data will be used.; Systematic Review Registration: INPLASY202040017.

Guokai, Z., et al. (2023). "Effectiveness and safety of lactic acid bacteria in improving cervical HPV infection&#xff1a;a systematic review and meta-analysis."
	
Gupta, A., et al. (2023). "Changes in Pelvic Floor Symptoms After Procedural Interventions for Uterine Leiomyomas: A Systematic Review." Obstetrics and Gynecology 142(2): 319-329.
	Objective: To conduct a systematic review to evaluate the effect of procedural interventions for leiomyomas on pelvic floor symptoms.; Data Sources: PubMed, EMBASE, and ClinicalTrials.gov were searched from inception to January 12, 2023, searching for leiomyoma procedures and pelvic floor disorders and symptoms, restricted to primary study designs in humans.; Methods of Study Selection: Double independent screening for studies of any study design in all languages that reported pelvic floor symptoms before and after surgical (hysterectomy, myomectomy, radiofrequency volumetric thermal ablation) or radiologic (uterine artery embolization, magnetic resonance-guided focused ultrasonography, high-intensity focused ultrasonography) procedures for management of uterine leiomyomas. Data were extracted, with risk-of-bias assessment and review by a second researcher. Random effects model meta-analyses were conducted, as feasible.; Tabulation, Integration, and Results: Six randomized controlled trials, one nonrandomized comparative study, and 25 single-group studies met criteria. The overall quality of the studies was moderate. Only six studies, reporting various outcomes, directly compared two procedures for leiomyomas. Across studies, leiomyoma procedures were associated with decreased symptom distress per the UDI-6 (Urinary Distress Inventory, Short Form) (summary mean change -18.7, 95% CI -25.9 to -11.5; six studies) and improved quality of life per the IIQ-7 (Incontinence Impact Questionnaire, Short Form) (summary mean change -10.7, 95% CI -15.8 to -5.6; six studies). There was a wide range of resolution of urinary symptoms after procedural interventions (7.6-100%), and this varied over time. Urinary symptoms improved in 19.0-87.5% of patients, and the definitions for improvement varied between studies. Bowel symptoms were inconsistently reported in the literature.; Conclusion: Urinary symptoms improved after procedural interventions for uterine leiomyomas, although there is high heterogeneity among studies and few data on long-term outcomes or comparing different procedures.; Systematic Review Registration: PROSPERO, CRD42021272678.; Competing Interests: Financial Disclosure Ethan Balk is a paid consultant to the Society for Gynecologic Research Systematic Review Group for his role as methodology expert. Sadikah Behbehani received payment from Intuitive Surgical. Mikio Nihira received payment from HealthTrust. David Sheyn receives research support from Renalis and consulting fees from Caldera Medical. He also received payment from CollaMedix. Alexandriah Alas receives payments for expert testimony and consulting. Kate Meriwether receives royalties from Elsevier publishing, is a consultant for RBI Medical and an unpaid investigator for Caldera Medical. The other authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Gupta, D., et al. (2020). "Myo-Inositol's Role in Assisted Reproductive Technology: Evidence for Improving the Quality of Oocytes and Embryos in Patients With Polycystic Ovary Syndrome." Cureus 12(5): e8079.
	Polycystic ovary syndrome (PCOS) is one of the most common causes of subfertility, and it is characterized by hormonal dysregulation like insulin resistance. Various measures have been taken in the past to overcome this insulin resistance to improve fertility treatment outcomes. The current paper aims to review and compare the existing studies and literature to assess the impact of myo-inositol (MI) on oocyte and embryo quality in assisted reproductive technology (ARTs). We thoroughly searched the PubMed and Google Scholar databases by using the keywords "PCOS, polycystic ovarian syndrome, inositol, oocyte quality, embryo quality, assisted conception, ART, IVF, and in vitro fertilization." Nine articles were finalized for review in this paper. Many of the reviewed studies have shown a trend toward the improvement of embryo quality in women with PCOS after MI supplementation; however, there is a lack of statistically significant evidence to support the use of MI in enhancing the quality of oocyte and/or embryo. Clear evidence regarding the role of MI in enhancing the quality of oocyte and embryo in PCOS is limited. A well-controlled, large, randomized controlled trial is required to definitively accept or refute its role.

Gurung, A., et al. (2022). "Effectiveness of Zingiber Officinale(ginger) compared with non-steroidal anti-inflammatory drugs and complementary therapy in primary dysmenorrhoea: A systematic review." Clinical Epidemiology and Global Health 18: 101152.
	Problem considered: The empirical evidence suggested the usage of ginger (zingiber officinale), complementary therapies and Non-steroidal anti-inflammatory drugs (NSAIDs) for dysmenorrhoea compared to self-administration of NSAIDs alone in alleviating the symptoms of dysmenorrhoea. However, there is a need for strong evidence to compare the effectiveness of ginger to that of complementary therapies like exercise, herbs (other than ginger) and NSAIDs. Thus, this systematic review aimed to compare the effectiveness of ginger with NSAIDs and other complementary therapies and suggests an effective dose of ginger in oral form that can be taken during dysmenorrhoea. Method(s): A systematic literature search was conducted using electronic databases, namely MEDLINE via PubMed, Cochrane central, Scopus, CINHAL, EBSCOhost, ProQuest Central, and Google Scholar search engine. The search terms were combined keywords related to menstrual pain, complementary therapy, NSAIDs, and ginger. Randomized or quasi-randomized controlled trials that included ginger as a comparator to assess the effect on primary dysmenorrhea were included in this systematic review. Data were extracted, and the findings were narratively synthesised. Result(s): An initial search from the electronic database identified 394 studies, of which eleven studies met the eligibility criteria, where seven were randomised controlled trials, and four were quasi-experimental studies. There was no significant difference between ginger and NSAIDs in decreasing pain intensity during menstruation. Ginger and exercises like muscle relaxation techniques, stretching, and sub-maximal aerobic exercise effectively reduce pain when combined. Dill seeds (Anethum graveolens, an aromatic herb used for flavouring and medical purposes) and ginger alone were effective in dysmenorrhoea, but no effect of valerian, peppermint and cumin (spices) seeds were observed. The effect of ginger was inclusive compared to placebo. Conclusion(s): The usage of ginger up to two grams per day in divided doses of powder or dietary form for three days from the first day of the menstrual cycle can be used safely for primary dysmenorrhoea. Ginger can be combined with complementary therapies like exercise for increased effectiveness in relieving menstrual pain. The alternative therapy can reduce dependency on synthetic drugs for controlling dysmenorrhoea. However, there is a need to carry out rigorous randomized controlled trials of longer duration to evaluate the effectiveness of ginger and auxiliary therapies other than ginger in controlling menstrual pain.Copyright © 2022 The Authors

Gurunthalingam, M. P., et al. (2023). "Prednisone and Live Birth Rate in Patients With Recurrent Implantation Failure." JAMA 330(10): 971-972.
	
Gurusamy, K., et al. (2020). "Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness." BMJ Open 10(5): e039314.
	Introduction: There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery.; Primary Objectives: To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis.; Secondary Objectives: To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis.; Methods and Analysis: We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting.; Ethics and Dissemination: This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal.; Prospero Registration Number: CRD42019130504.; Competing Interests: Competing interests: The clinical practice of the clinicians in the project: TM, MM, MS, OA and SO may be altered by the findings of the review. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Gustavo, F., et al. (2021). "Evaluation of safety and effectiveness of Gestrinone in the treatment of endometriosis: a systematic review."
	
Gutierrez, M., et al. (2023). "Open-label, phase I, dose escalation/expansion trial of the anti-SIRPalpha monoclonal antibody BI 770371 in patients with advanced solid tumours, alone or in combination with the anti-PD-1 monoclonal antibody ezabenlimab." Annals of Oncology 34(Supplement 2): S485.
	Background: BI 770371, a pan-specific anti-signal regulatory protein alpha (SIRPalpha) monoclonal antibody (mAb), reactivates innate and adaptive anti-tumour immune responses. This phase I, non-randomised, open-label, multicentre trial (NCT05327946) aimed to determine the maximum-tolerated dose (MTD) and recommended dose for expansion of BI 770371 +/- ezabenlimab. Method(s): BI 770371 was administered alone or in combination with ezabenlimab IV once every 3 weeks in patients with advanced solid tumours. Treatment continued until progressive disease, unacceptable toxicity or other withdrawal criteria. Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control. Primary endpoint was dose-limiting toxicities (DLTs) in the MTD evaluation period. Secondary endpoints were adverse events (AEs) and DLTs in the on-treatment period. Result(s): As of 31 March 2023, 18 patients (monotherapy, n=15; combination therapy, n=3) have been treated in Canada, Japan and the US. In the patients who received monotherapy, the most common tumour types were colorectal, ovarian and prostate cancer (n=2 patients with each). 53% of patients were male, 53% had ECOG PS 0 and all had received >2 prior lines of treatment. AEs were reported in 12 patients (80%) and grade 3 AEs were reported in one patient (peripheral oedema, atrial fibrillation). Treatment-related AEs were observed in 10 patients (67%; all grade 1/2); the most common were pruritus (n=5) and peripheral oedema (n=2). Serious AEs were reported in four patients (27%; atrial fibrillation, decreased appetite, encephalitis, hypoxia, disease progression). Only one patient had an AE leading to treatment discontinuation (encephalitis). In 14 evaluable patients, 11 (73%) achieved a best response of stable disease. In the MTD evaluable set (n=15 monotherapy, n=3 combination therapy), no DLTs were reported during the MTD evaluation period. The MTD has not been reached; dose escalation is ongoing. Conclusion(s): BI 770371 showed manageable toxicity alone and in combination with ezabenlimab. The trial is ongoing. Clinical trial identification: NCT05327946. Editorial acknowledgement: Medical writing support for the development of this abstract, under the direction of the authors, was provided by Frans Everson, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim Legal entity responsible for the study: Boehringer Ingelheim. Funding(s): Boehringer Ingelheim. Disclosure: M. Gutierrez: Financial Interests, Personal, Advisory Board: Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Guardant; Financial Interests, Personal, Other, Consulting: Celularity, Merck. R. Jamal: Financial Interests, Personal, Advisory Board: BMS, Medison Pharma; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, Bristol Myers Squibb, Iovance Biotherapeutics; Financial Interests, Institutional, Principal Investigator: Princiapal Investigaor in multiple industry led trial. N. Yamamoto: Financial Interests, Personal, Invited Speaker: ONO, Chugai, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Eisai, Takeda, Boehringer Ingelheim, Cimic, Chugai, Healios; Financial Interests, Institutional, Local PI, Principal Investigator in industry sponsored trial: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka; Financial Interests, Institutional, Local PI, Principal investigator in industry sponsored trial: Carna Biosciences, Genmab, Shionogi, TORAY; Financial Interests, Institutional, Research Grant, Principal investigator in industry sponsored trial: Rakuten Medical, InventisBio Co., Ltd. T. Doi: Financial Interests, Personal, Other, Advisory Role: Noile-Immune Biotech, Oncolys BioPharma, Boehringer Ingelheim, A2 Healthcare, Nano Carrier, PRA Health Sciences, Kaken Pharma, Chugai Pharma, Sumitomo Pharma, Shionogi, Otsuka Pharma, Takeda, Kyowa rin, Rakuten Medical, Giliad; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho, MSD, AbbVie, Eisai, Pfizer, BMS, Janssen Pharma, Daiichi Sankyo, Chugai Pharma, Boehringer Ingelheim, PRA Health Sciences, Amgen, GSK, Shionogi, RIN Institute, ONO Pharma. M. Elgadi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J.L. Ferrada: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. S.M. Wojciekowski: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M.R. Patel: Financial Interests, Personal, Leadership Role: ION Pharma; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Speaker, Consultant, Advisor: Olema Pharmaceuticals; Financial Interests, Institutional, Research Funding: Acerta Pharma, ADC Therapeutics, Agenus, Aileron Therapeutics, AstraZeneca, BioNTech AG, Boehringer Ingelheim, Celgene, CicloMed, Clovis Oncology, Cyteir Therapeutics, Daiichi Sankyo, Lilly, Evelo Therapeutics, Evelo Therapeutics, Genentech/Roche, Gilead Sciences, GSK, H3 Biomedicine, Hengrui Therapeutics, Hutchison MediPharma, Jacobio, Janssen, Klus Pharma, Kymab, Loxo, LSK Biopartners, Lycera, Macrogenics, Merck, Millennium, Mirati Therapeutics, Moderna Therapeutics, Pfizer, Prelude Therapeutics, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Taiho Pharmaceutical, Tesaro, TopAlliance BioSciences Inc., Vigeo, ORIC, Artios, Treadwell, Mabspace, IgM Biosciences, Puretech, Artios, BioTheryX, Black Diamond Therapeutics, IgM Biosciences, NGM Biopharmaceuticals, Novartis, nurix, Relay Therapeutics, Samumed, Silicon Therapeutics, TeneoBio, Treadwell Therapeutics, Zymeworks, Olema, Adagene, Astellas, NGM, Accutar Biotech, Nurix, Novartis, Compugen, Black Diamond Therapeutics, Relay Therapeutics, Artios, Treadwell Therapeutics, MabSpace Biosciences, Immunogen, Blueprint Pharmaceuticals, Accutar, Artios, Bayer, Bicycle Therapeutics, BioTheryX, Compugen, Cullinan Oncology, Erasca, Inc., Immune-Onc Therapeutics, Immunitas, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Novartis, ORIC Pharmaceuticals, Pionyr, Revolution Medicines, Ribon Therapeutics, Step Pharma, Syndax, Synthorx, Xencor.Copyright © 2023 European Society for Medical Oncology

Güven Cenk, M. and D. Uysal (2023). "In-bag abdominal manual morcellation versus contained power morcellation in laparoscopic myomectomy: a comparison of surgical outcomes and costs." BMC surgery 23(1): 106.
	Background: To compare the surgical outcomes and costs of in-bag abdominal manual morcellation (AMM) and contained power morcellation (PM) in laparoscopic myomectomy.; Methods: A total of 61 patients were divided into two groups based on their myomectomy specimen extraction methods: AMM group (n = 33) and electromechanical contained PM group (n = 28). The surgical outcomes and cost were compared between groups. During AMM, a glove bag (in 27 patients) and an endo bag were used (in 6 patients) according to the myoma size.; Results: Morcellation time (18 ± 9.2 min vs. 37.4 ± 14.1 min) and total operation time (100 ± 24.3 min vs. 127 ± 33.1 min) were significantly lower in the AMM group compared to those in the PM group. Other surgical outcomes, which were similar between groups, included delta hemoglobin, length of hospital stay and VAS score at 12 and 24 h postoperatively. There were no per- or postoperative complications in both group with no conversion to laparotomy. One patient was transfused with two units of erythrocyte suspension postoperatively in the PM group. Sarcoma was not diagnosed in any of the cases in both group.; Conclusion: The in-bag AMM or contained PM for specimen extraction resulted in similar outcomes in terms of delta hemoglobin, postoperative pain intensity (VAS score at 12 and 24 h postoperatively), the need for additional analgesia, and the length of hospital stay; however, total operation time and morcellation time were significantly shorter in the AMM group, indicating a prominent advantage. Significant cost-effectiveness is also a critical advantage of in-bag AMM compared to containing PM. (© 2023. The Author(s).)

Guy, L., et al. (2019). "Effectiveness of Pacing as a Learned Strategy for People With Chronic Pain: A Systematic Review." The American journal of occupational therapy : official publication of the American Occupational Therapy Association 73(3): 7303205060p7303205061-7303205060p7303205010.
	IMPORTANCE: Pacing is a key pain management strategy used by occupational therapy practitioners when working with people with chronic pain. However, there is a paucity of evidence and a lack of consensus regarding the effectiveness of pacing as a pain management strategy for people with chronic pain. OBJECTIVE: To evaluate the evidence for the effectiveness of pacing as a learned strategy for people with chronic pain. DATA SOURCES: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to undertake a systematic review. Six databases were searched in March 2016 for randomized controlled trials (RCTs). Combinations of keywords and MeSH terms were used as search terms. STUDY SELECTION AND DATA COLLECTION: We sought intervention studies that included participants using pacing as a strategy. Studies were assessed for eligibility on the basis of predetermined criteria. Of the 2,820 articles located, 7 RCTs met inclusion criteria. FINDINGS: Pacing does not reduce the severity of pain or alter psychological traits; however, it can assist in lessening joint stiffness and the interference of fatigue and in decreasing the variability of physical activity. CONCLUSIONS AND RELEVANCE: Current evidence supports the delivery of a learned pacing intervention to reduce the interference of fatigue, reduce joint stiffness, and decrease physical activity variability but does not support the use of learned pacing to reduce pain severity. Future research should investigate the effectiveness of pacing as a pain management strategy within the International Classification of Functioning, Disability and Health domains of activity and participation. WHAT THIS ARTICLE ADDS: This systematic review examines existing research on pacing as a learned intervention strategy. The findings will support the clinical reasoning of occupational therapy practitioners, to determine when a learned pacing strategy is indicated, and considerations for how it may be delivered.

Guzek, D., et al. (2023). "Effect of Vitamin D Supplementation on Depression in Adults: A Systematic Review of Randomized Controlled Trials (RCTs)." Nutrients 15(4).
	Vitamin D is a nutrient potentially beneficial in the treatment of depression. The study aimed to carry out a systematic review of the studies assessing the influence of vitamin D supplementation on depression within Randomized Controlled Trials (RCTs). The systematic review was prepared on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020155779). The peer-reviewed studies available within PubMed or Web of Science databases until September 2021 were taken into account. The number of screened records was 8514, and 8 records were included. Two independent researchers conducted screening, including, reporting, and risk of bias assessment using the revised Cochrane risk-of-bias tool for randomized trials. The included studies presented a population of patients with major depressive disorders or general depression, as well as bipolar depression or postpartum depression. The majority of included studies were conducted for 8 weeks or 12 weeks, while one study was conducted for 6 months. Within the large number of included studies, a daily dose of 1500 IU, 1600 IU, or 2800 IU was applied, while within some studies, a vitamin D dose of 50,000 IU was applied weekly or biweekly. Among applied psychological measures of depression, there were various tools. In spite of the fact that the majority of included studies (five studies) supported the positive effect of vitamin D supplementation for the psychological measure of depression, for three studies the positive influence was not supported. A medium risk of bias was indicated for six studies, while a high risk of bias was defined for only two studies, due to deviations from the intended interventions and in measurement of the outcome, as well as for one study, also arising from the randomization process and due to missing outcome data. Based on conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of the medium risk of bias, while two studies of a medium risk of bias did not support it. Taking this into account, the conducted systematic review is not a strong confirmation of the effectiveness of vitamin D supplementation in the treatment of depression.

Guzene, L., et al. (2023). "Assessing Interobserver Variability in the Delineation of Structures in Radiation Oncology: A Systematic Review." International journal of radiation oncology biology physics 115(5): 1047-1060.
	Purpose: The delineation of target volumes and organs at risk is the main source of uncertainty in radiation therapy. Numerous interobserver variability (IOV) studies have been conducted, often with unclear methodology and nonstandardized reporting. We aimed to identify the parameters chosen in conducting delineation IOV studies and assess their performances and limits. Methods and Materials: We conducted a systematic literature review to highlight major points of heterogeneity and missing data in IOV studies published between 2018 and 2021. For the main used metrics, we did in silico analyses to assess their limits in specific clinical situations. Result(s): All disease sites were represented in the 66 studies examined. Organs at risk were studied independently of tumor site in 29% of reviewed IOV studies. In 65% of studies, statistical analyses were performed. No gold standard (GS; ie, reference) was defined in 36% of studies. A single expert was considered as the GS in 21% of studies, without testing intraobserver variability. All studies reported both absolute and relative indices, including the Dice similarity coefficient (DSC) in 68% and the Hausdorff distance (HD) in 42%. Limitations were shown in silico for small structures when using the DSC and dependence on irregular shapes when using the HD. Variations in DSC values were large between studies, and their thresholds were inconsistent. Most studies (51%) included 1 to 10 cases. The median number of observers or experts was 7 (range, 2-35). The intraclass correlation coefficient was reported in only 9% of cases. Investigating the feasibility of studying IOV in delineation, a minimum of 8 observers with 3 cases, or 11 observers with 2 cases, was required to demonstrate moderate reproducibility. Conclusion(s): Implementation of future IOV studies would benefit from a more standardized methodology: clear definitions of the gold standard and metrics and a justification of the tradeoffs made in the choice of the number of observers and number of delineated cases should be provided.Copyright © 2022 Elsevier Inc.

Gwacham Nnamdi, I., et al. (2021). "Neoadjuvant chemotherapy followed by fertility sparing surgery in cervical cancers size 2-4 cm; emerging data and future perspectives." Gynecologic Oncology 162(3): 809-815.
	Background: Approach to the management of early stage cervical cancers with tumor size >2 cm in women who desire fertility preservation has been fraught with controversy. Fertility sparing surgery for FIGO 2018 stage IB cancers has been validated most for tumors ≤2 cm. In this review, our objective was to evaluate the oncologic and obstetric outcomes for women that underwent neoadjuvant chemotherapy (NACT) before fertility sparing surgery for tumors 2-4 cm.; Methods: We performed a systematic literature review and searched PubMed, Google Scholar, Cochrane Reviews and UpToDate (from January 2000 to February 2021) using the terms: cervical cancer, fertility preservation, trachelectomy, radical trachelectomy, neoadjuvant chemotherapy, cervical cancer treatment, stage IB1 or IB2 cervical cancer, and cervical cancer size 2-4 cm. We included manuscripts with information on patients with tumor sizes 2-4 cm, lymph node status, follow-up, obstetric and oncologic outcome. We excluded review articles or articles without all pertinent patient information.; Results: Eighteen articles were identified including 249 patients. For final analysis, 114 met inclusion criteria. All included patients had FIGO 2018 stage IB2 cervical cancer, underwent neoadjuvant chemotherapy and subsequent fertility sparing surgery. Vaginal radical trachelectomy, cold knife conization, abdominal radical trachelectomy, laparoscopic radical trachelectomy, simple vaginal trachelectomy, and cone laser were performed in 46 (40.4%), 26 (22.8%), 14 (12.3%), 13 (11.4%), 8 (7%), and 7 (6.1%) women, respectively. The most common regimen of chemotherapy was platinum-based therapy with cisplatin. The follow-up time reported in all studies ranged from 1 to 225 months. Of 64 attempted pregnancies, there were 49 (76.6%) viable deliveries which included 6 preterm births (9.4%). The recurrence rate was 6.1% and two patients (1.8%) died of disease.; Conclusion: Fertility sparing surgery following NACT is an option for women with cervical cancers that are 2-4 cm that wish to preserve fertility without sacrificing oncologic or obstetric outcomes. Confirmation of these findings are anticipated from an ongoing international phase II clinical trial [1].; Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest associated with this review article. (Copyright © 2021 Elsevier Inc. All rights reserved.)

gykpj, R. B. R. (2022). "The Effect of Hypopressive training improves Postpartum Belly, urine Loss and Abdominal Strength." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: G11.427.410.698.277 This is a randomized, controlled, blinded clinical trial. Intervention Group (IC): 22 women selected, randomized by a blinded researcher, who present at least 2 cm of diastasis of the rectus abdominis at some point in the linea alba, measured by ultrasound at rest. The measurement will be taken at the umbilical line, 2 centimeters above and 2 centimeters below the navel line. They will receive the original hypopressive method training for 12 weeks, 2 times a week for 30 minutes by a trainer qualified for the hypopressive method. Control Group (CG): 22 women selected randomly by a blinded researcher, who present at least 2 cm of diastasis of the rectus abdominis at some point in the linea alba, measured by ultrasound at rest. The measurement will be made at the umbilical line, 2 centimeters above and 2 centimeters below the navel line at rest in the supine position and in trunk flexion. They will not receive any type of intervention during the period under analysis and after the IC intervention they will receive the same treatment in the same period. Both groups will not be able to do physical exercises concomitantly with the intervention period and did not use any type of orthosis, belt or abdominal band. The ultrasound evaluation will be performed before the beginning of the intervention and shortly after 12 weeks of the first group by a blinded researcher. CONDITION: M62.0 Unspecified urinary incontinence PRIMARY OUTCOME: The hypopressive training method is expected to approach 5% of the borders of the rectus abdominis at one of the diastasis points along the linea alba assessed by imaging ultrasound.; SECONDARY OUTCOME: It is expected that the hypopressive training method will improve abdominal function by 5%, assessed by the plank test, in addition to improving the pelvic floor complaints by 5% of the Pelvic Floor Questionnaire scores. INCLUSION CRITERIA: Will be included women aged 18 or over; between 45 days and si Xmonths postpartum; with diagnosis of diastasis, considered as from 2 cm of distance at a point of the extension of the linea alba, no history of previous abdominal aesthetic surgeries; do not have musculoskeletal disease that makes it impossible to perform the requested exercises.

H Al Wattar, B., et al. (2022). "Lifestyle interventions in women with polycystic ovary syndrome: A scoping systematic review of randomised evidence." Semergen 48(3): 186-194.
	Objective: Lifestyle interventions (LSI) are recommended as first-line treatment for polycystic ovary syndrome (PCOS), yet the strength of evidence underpinning LSIs effectiveness remains unclear. We systematically reviewed the literature on LSIs in PCOS, evaluated evidence quality and summarised recommendations for clinical practice.; Material and Methods: We searched MEDLINE, EMBASE and CENTRAL for all randomised trials evaluating any LSI in PCOS until April 2021. We extracted data on the LSIs' characteristics, dietary composition, duration, implementation, compliance assessment, and reported outcomes. We evaluated the evidence gap using a network-map of evaluated interventions.; Results: We screened 550 citations and included 79 trials (n=4659 women). Most trials were from high-income countries (57/79, 72%) over a decade ago (48/79, 61%) and enrolled obese/overweight women (57/77, 74%). BMI was the commonest reported outcome (58/79, 73%), followed by weight (49/79, 62%), and testosterone (45/79, 57%). More than half of the trials had high-risk of randomisation (51/79, 65%) and allocation bias (49/79, 62%). Only 27 were registered prospectively (27/79, 34%). Two-thirds evaluated a dietary intervention (70/79, 88%), most commonly a hypocaloric diet (32/70, 46%); nineteen evaluated a combined dietary with pharmacological intervention (19/79, 24%), six combined diet with physical or behavioural intervention (6/79, 8%), and only one trial included all four elements.; Conclusions: Evidence on LSI in PCOS is of poor quality with high variations in trial design, comparisons, and outcome reporting. Hypocaloric diet is the most commonly recommended LSI intervention for primary care. Future trials are needed to evaluate pragmatic and simple LSIs in robust multicenter studies.; Prospero Registration: CRD42020186571. (Copyright © 2021 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Haahr, T., et al. (2023). "Effect of clindamycin and a live biotherapeutic containing lactobacilli on the reproductive outcomes of IVF patients with abnormal vaginal microbiota: a double-blind, placebo-controlled multicentre trial." Human Reproduction 38(Supplement 1): i160-i161.
	Study question: Does treatment of abnormal vaginal microbiota improve the reproductive outcomes of IVF patients? Summary answer: Data is being analysed and will be presented at ESHRE 2023. What is known already: An increasing number of studies reported an association between abnormal genital tract microbiota and adverse reproductive outcomes in IVF patients. One hypothesis could be that vaginal microbiota ascend to the endometrium where the microbiota hampers implantation. To the best of our knowledge, this is the first study powered to investigate causality between abnormal genital tract microbiota-in this study defined by a bacterial vaginosis like vaginal microbiota-and clinical pregnancy rate in IVF patients. Study design, size, duration: Double-blind, placebo-controlled multicentre trial in IVF patients diagnosed with abnormal vaginal microbiota and subsequently randomised into three parallel groups 1:1:1. The first group received clindamycin 300 mg x2 daily for 7 days followed by vaginal Lactobacillus crispatus until the clinical pregnancy scan. The second group received clindamycin and placebo, whereas the third group received placebo/placebo. A total of 1518 patients were screened, and 338 patients were randomised. The study duration was from 2017 to 2023. Participants/materials, setting, methods: IVF patients with any cause of infertility embarking on their first, second or third IVF stimulation cycle or embryo transfer were approached for inclusion. At a minimum 12 days prior to embryo transfer, patients were screened for abnormal vaginal microbiota defined by a qPCR assay, targeting high quantitative loads of Fannyhessea vaginae and Gardnerella spp. Patients were excluded if they had intrauterine malformations like polyps, septum, and fibroma. Main results and the role of chance: Data and safety monitoring board has decided not to open the randomization code yet. The final dataset is being completed. Data is being analysed and will be presented at ESHRE 2023. Limitations, reasons for caution: Data is being analysed and will be presented at ESHRE 2023. Wider implications of the findings: The present drug intervention study used clindamycin and a live biotherapeutic containing Lactobacillus crispatus. The results of the study could have a worldwide important clinical impact on daily IVF practice as currently there is no evidence that screening and treating IVF patients with abnormal vaginal microbiota improves the reproductive outcome.

Haase Christiane, L., et al. (2023). "Association between body mass index, weight loss and the chance of pregnancy in women with polycystic ovary syndrome and overweight or obesity: a retrospective cohort study in the UK." Human reproduction (Oxford, England) 38(3): 471-481.
	Study Question: What are the associations between baseline BMI (Study 1) and change in body weight (Study 2) with the likelihood of pregnancy in women with polycystic ovary syndrome (PCOS).; Summary Answer: In women with PCOS, higher baseline BMI was associated with a lower chance of pregnancy; however, weight loss was associated with an increased chance of pregnancy versus maintaining a stable weight or gaining weight.; What Is Known Already: Two studies in large cohorts of Danish women with the intention to become pregnant showed a decline in fecundability ratios with higher BMI. Furthermore, a meta-analysis found that overweight/obesity significantly worsened metabolic and reproductive outcomes in women with PCOS.; Study Design, Size, Duration: Data were extracted from the UK Clinical Practice Research Datalink GOLD database. Patients included women aged 18-45 years with BMI ≥18.5 (Study 1) or ≥25 kg/m2 (Study 2) at time of PCOS diagnosis (index date). The primary outcome was the time to first pregnancy recorded during 36-months' follow-up, analysed with Cox proportional hazard models and presented as hazard ratios (HRs).; Participants/materials, Setting, Methods: Study 1 included 9955 women with PCOS. Study 2 included 7593 women with PCOS and median BMI of 34.0 kg/m2.; Main Results and the Role of Chance: Higher BMI was associated with a lower chance of pregnancy in the 3 years following diagnosis. It was estimated that 41% of women with normal weight (18.5-24.9 kg/m2) would become pregnant compared to 17% of women with obesity class III (BMI ≥40.0 kg/m2) during follow-up. Furthermore, the chance of pregnancy for women with obesity class III was estimated to be 63% lower than for women with normal weight, with the same age and glycaemic status (HR 0.37, 95% CI 0.31-0.44; P < 0.0001). A significant inverse association was found between BMI change and chance of pregnancy: 10% weight loss was estimated to increase the chance of pregnancy by 68% for women with baseline BMI of 40 kg/m2 (HR 1.68, 95% CI 1.49-1.90).; Limitations, Reasons for Caution: Multiple factors influence the chance of pregnancy (the ability and willingness to become pregnant), which was addressed by exclusion criteria employed. The real-world nature of the study means that use of non-prescription contraceptives was not available. Bias may have been introduced by the fact that only around 40% of women with PCOS in the CPRD GOLD database had their BMI recorded during the year prior to PCOS diagnosis. BMI categories used in the analyses may not be applicable to women of all ethnicities. The study population was only representative of women in the UK and results may not be generalizable to other regions. PCOS diagnoses were based on codes entered into the system by primary care providers, and no information was available regarding the criteria used for diagnosis, although symptoms used to diagnose PCOS have not changed over time.; Wider Implications of the Findings: Our observations provide further evidence of the benefits of weight loss in women with overweight/obesity and PCOS who are seeking to become pregnant.; Study Funding/competing Interest(s): Novo Nordisk A/S. A.H.B. declares fees for consultancy from Novo Nordisk. P.N.L. and C.L.H. are employees of Novo Nordisk. V.S. and A.V. are employees of, and hold shares in, Novo Nordisk.; Trial Registration Number: N/A. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Habib, N., et al. (2022). "Impact of lifestyle and diet on endometriosis: a fresh look to a busy corner." Przeglad menopauzalny = Menopause review 21(2): 124-132.
	Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.; Competing Interests: The authors report no conflict of interest. (Copyright © 2022 Termedia.)

Habiburrahman, M., et al. (2023). "Quercetin as a noteworthy treatment for polycystic ovary syndrome: An evidence-based review from molecular basis mechanism to clinical perspective." Obesity Medicine 39: 100490.
	Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that often occurs in reproductive-age women and causes anovulatory infertility problems. Current management guidelines, including fertility medications, hormonal therapy, and glycemic control, have drawbacks due to their limited efficacy and undesirable outcomes. Therefore, this review intended to scrutinise the mechanism and potential benefits of a candidate herbal therapy for PCOS, quercetin, as an adjunctive medication to alleviate disease manifestations. Articles were searched in PubMed, EBSCOHost, ProQuest, and Scopus databases and screened based on their titles and abstracts. A critical appraisal was done using an Evidence-Based Medicine worksheet. Fourteen eligible articles were obtained, including one systematic review, four randomized clinical trials; eight experimental studies; and one systematic pharmacological strategy-based research. It was shown that quercetin alleviated insulin resistance via activating phosphatidylinositol 3-kinase (PI3-K) signalling, reduced testosterone, controlled luteinising hormone, and had anti-inflammatory effects on the ovaries. This antioxidant also altered catabolism and steroidogenesis, regulated AMP-activated protein kinase (AMPK), and decreased oocyte nucleation failure. Furthermore, the lipid profile was reduced by quercetin through the modulation of adiponectin receptors. Ultimately, quercetin successfully improved the pregnancy rate. Due to its potential to modulate several pathways involved in metabolic disease and infertility, quercetin is a promising candidate in clinical practice as adjunctive therapy for PCOS.Copyright © 2023 Elsevier Ltd

Hadi, A., et al. (2020). "Effect of probiotics and synbiotics on selected anthropometric and biochemical measures in women with polycystic ovary syndrome: a systematic review and meta-analysis." European Journal of Clinical Nutrition 74(4): 543-547.
	This study aimed to systematically review randomized clinical trials (RCTs) to clarify the effects of pro-/synbiotic supplementation on anthropometric and biochemical measurements in women with polycystic ovary syndrome (PCOS). PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar were searched through September 2018. Eight RCTs (nine treatment arms) were included. Pro-/synbiotic supplementation significantly reduced fasting blood sugar (-2.52 mg/dl, 95% confidence interval (CI): -4.10 to -0.95), insulin (-2.27 µIU/mL, 95% CI: -3.40 to -1.14), homeostasis model assessment for insulin resistance index (-0.69, 95% CI: -0.98 to -0.40), C-reactive protein (-1.69 Hedges', 95% CI: -3.00 to -0.38), and total testosterone (-0.12 ng/mL, 95% CI: -0.17 to -0.08) in women with PCOS. However, changes in the mean difference of weight and body mass index did not reach a statistically significant level. The findings suggest that pro-/synbiotic supplementation may improve glucose homeostasis parameters, hormonal, and inflammatory indices in women with PCOS.

Hafermann, J., et al. (2024). "Efficacy and safety of V-LocTM barbed sutures versus conventional suture techniques in gynecological surgery: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 309(4): 1249-1265.
	Purpose: One of the most challenging tasks in laparoscopic gynecological surgeries is suturing. Knotless barbed sutures are intended to enable faster suturing and hemostasis. We carried out a meta-analysis to compare the efficacy and safety of V-LocTM barbed sutures (VBS) with conventional sutures (CS) in gynecological surgeries. Method(s): We systematically searched PubMed and EMBASE for studies published between 2010 and September 2021 comparing VBS to CS for OB/GYN procedures. All comparative studies were included. Primary analysis and subgroup analyses for the different surgery and suturing types were performed. Primary outcomes were operation time and suture time; secondary outcomes included post-operative complications, surgical site infections, estimated blood loss, length of stay, granulation tissue formation, and surgical difficulty. Results were calculated as weighted mean difference (WMD) or risk ratio (RR) and 95% confidence intervals (CI) with a random effects model, and a sensitivity analysis for study quality, study size, and outlier results was performed. PROSPERO registration: CRD42022363187. Result(s): In total, 25 studies involving 4452 women undergoing hysterectomy, myomectomy, or excision of endometrioma. VBS were associated with a reduction in operation time (WMD - 17.08 min; 95% CI - 21.57, - 12.59), suture time (WMD - 5.39 min; 95% CI - 7.06, - 3.71), surgical site infection (RR 0.26; 95% CI 0.09, 0.78), estimated blood loss (WMD - 44.91 ml; 95% CI - 66.01, - 23.81), granulation tissue formation (RR 0.48; 95% CI 0.25, 0.89), and surgical difficulty (WMD - 1.98 VAS score; 95% CI - 2.83, - 1.13). No difference between VBS and CS was found regarding total postoperative complications or length of stay. Many of the outcomes showed high heterogeneity, likely due to the inclusion of different surgery types and comparators. Most results were shown to be robust in the sensitivity analysis except for the reduction in granulation tissue formation. Conclusion(s): This meta-analysis indicates that V-LocTM barbed sutures are safe and effective in gynecological surgeries as they reduce operation time, suture time, blood loss, infections, and surgical difficulty without increasing post-operative complications or length of stay compared to conventional sutures.Copyright © The Author(s) 2023.

Hafidh, B., et al. (2022). "Vasopressin to Control Blood Loss during Hysterectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Journal of Minimally Invasive Gynecology 29(3): 355-364.e352.
	Objective: Minimizing intraoperative blood loss during hysterectomy is crucial to lessen associated perioperative morbidity. The aim of this investigation is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that compared vasopressin versus normal saline in controlling intraoperative blood loss during hysterectomy. Data Sources: We screened 5 major databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials) from inception till July 18, 2021. We used the following query search in all databases: (vasopressin OR arginine vasopressin OR argipressin OR antidiuretic hormone) AND (hysterectomy) AND (saline OR placebo OR control OR no treatment) AND (randomized OR randomised OR randomly). There was no language restriction during database screening. Methods of Study Selection: We considered all studies that met the following evidence-based criteria: (1) patients: individuals undergoing hysterectomy for any indication, (2) intervention: vasopressin, (3) comparator: normal saline, placebo, or no treatment, (4) outcomes: reliable extraction of any of our endpoints, and (5) study design: RCTs. We assessed risk of bias of included studies and pooled endpoints as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). We performed statistical analysis using the Review Manager software, version 5.4.0. Tabulation, Integration, and Results: Seven RCTs with an overall low risk of bias met the inclusion criteria. This meta-analysis included a total of 455 patients; 232 and 223 patients were allocated to vasopressin and control group, respectively. The majority of RCTs were vaginal hysterectomy (n = 5), few abdominal hysterectomy, (n = 2) and no laparoscopic hysterectomy. The mean estimated intraoperative blood loss was significantly lower in favor of the vasopressin group compared with the control group (n = 6 RCTs, MD = -119.85 mL, 95% CI [-177.55, -62.14], p <.001). However, there was no significant difference between both groups regarding mean operating time, mean change in postoperative hemoglobin, mean hospital stay, rate of febrile morbidity, rate of pelvic infection, rate of perioperative blood transfusion, and rate of perioperative complications. Conclusion(s): Compared with normal saline, vasopressin significantly reduced the estimated blood loss during hysterectomy but did not change any clinically significant outcomes. In addition, vasopressin was safe and did not correlate with an increase in the rates of febrile morbidity or pelvic infection.Copyright © 2021 AAGL

Hagen, S., et al. (2019). "Effectiveness and cost-effectiveness of basic versus biofeedback-mediated intensive pelvic floor muscle training for female stress or mixed urinary incontinence: Protocol for the OPAL randomised trial." BMJ Open 9(2): e024153.
	Introduction Accidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence. Methods and analysis This multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score. Ethics and dissemination Approval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review. Trial registration number ISRCTN57746448; Pre-results.Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Hagovska, M., et al. (2021). "A randomized, intervention parallel multicentre study to evaluate duloxetine and innovative pelvic floor muscle training in women with uncomplicated stress urinary incontinence-the DULOXING study." International Urogynecology Journal 32(1): 193-201.
	INTRODUCTION AND HYPOTHESIS: The aim of our study was to evaluate the effect of a combination of innovative pelvic floor muscle training (iPFMT) and duloxetine compared with the use of duloxetine alone on women with stress urinary incontinence (SUI) after 12 weeks of treatment. METHODS: We conducted a parallel multicentre study with randomized intervention in 45 national urological outpatient clinics. Patients with an enrolment ratio of 1:1 were divided into the experimental and control groups. The following were used for evaluation: incontinence episode frequency (IEF)/week, the International Consultation on Incontinence Questionnaire (ICIQ-SF), the Urinary Incontinence Quality of Life Scale (I-QoL) and the Patient Global Impression of Improvement (PGI-I). The experimental group received oral treatment with duloxetine (a daily dose of 40 mg BID) and innovative pelvic floor muscle training (iPFMT). The control group received only oral treatment with duloxetine at a daily dose of 40 mg BID. RESULTS: The number of women who were evaluated was 158. The control group comprised 79 women with an average age of 56.8 ± 13.8 years and the experimental group comprised 79 women with an average age of 53.4 ± 11.9 years. There were no significant differences in pre-treatment parameters. For the intent-to-treat analysis after 12 weeks' treatment, significant differences were observed between the experimental vs. control group (p < 0.001) for the following variables: IEF/week decrease (66.7% vs. 50.0%); ICIQ-UI SF decrease (8.3 ± 3.8 vs. 9.7 ± 4.2); PGI-I (70.8% vs. 65.6%); I-QoL score increase (19.3% vs. 6.6%). CONCLUSION: The addition of iPFMT to duloxetine treatment improves SUI syndrome in women compared with duloxetine treatment alone. REGISTRATION: Clinical Trials.gov NCT04140253.

Hagovska, M., et al. (2023). "A randomised interventional parallel study to evaluate the effect of different frequencies of pelvic floor muscle exercises with core stabilisation using three-dimensional ultrasound: the PELSTAB study." International Urogynecology Journal 34(9): 2049-2060.
	Introduction and hypothesis: The primary objective was to compare high- and low-frequency pelvic floor muscle training (PFMT) with the impact on urinary incontinence episode frequency over 1 week (IEF/week). The secondary objective was to compare the two groups with regard to pelvic floor muscle function, morphometry, incontinence quality of life, and patient global impression. Method(s): This was a randomised parallel controlled study. The setting was regional gynaecological and urological outpatient clinics. The subjects consisted of a sample of 86 women with stress urinary incontinence (SUI). Group A underwent high-frequency PFMT and group B underwent low-frequency PFMT for 12 weeks. We recorded the IEF/week. The International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF) was used. Pelvic floor muscle function was evaluated using a perineometer. Pelvic floor muscle morphometry was evaluated with 3D/4D ultrasound. The Urinary Incontinence Quality of Life Scale (I-QoL) was used. Result(s): Significant differences between group A and B after treatment (p<0.001) were noted in favour of group A in IEF/week (group A 10.2+/-7.0/2.3+/-3.0 vs group B 9.3+/-4.7/6.3+/-4.9), in the ICIQ-UI SF (group A 9.7+/-3.0/3.7 +/- 3.6 vs group B 9.9+/-3.2/9.4+/-3.4). Significant differences between groups A and B after treatment were noted in favour of group A for pelvic floor muscle function in terms of maximal voluntary contraction and its duration, and also for pelvic floor muscle morphometry in terms of a reduction of the hiatal area during rest, contraction, and the Valsalva manoeuvre. Conclusion(s): High-frequency PFMT for 12 weeks significantly decreased IEF/week in comparison with low-frequency PFMT. In the high-frequency exercise group, women had significantly better pelvic floor muscle function, morphometry and quality of life than the low-frequency exercise group.Copyright © 2023, The International Urogynecological Association.

haihong, w., et al. (2023). "Efficacy and safety of pabolizumab in the treatment of common cancers of the female reproductive tract: a systematic review and meta-analysis of randomized controlled trials."
	
Hailan, Y., et al. (2022). "Oral Gonadotropin-Releasing Hormone Antagonists in the treatment of Endometriosis-Associated pain: A Systematic Review and Network Meta-analysis of Efficacy and Safety Parameters." PROSPERO International prospective register of systematic reviews.
	
Haiyu, Z., et al. (2021). "Efficacy and safety of External Therapy of TCM for primary dysmenorrhea: a protocol for systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Hajek, J., et al. (2021). "A randomised, multi-center, open trial comparing a semi-automated closed vitrification system with a manual open system in women undergoing IVF." Human reproduction (Oxford, England) 36(8): 2101‐2110.
	STUDY QUESTION: What are outcome and procedural differences when using the semi‐automated closed Gavi® device versus the manual open Cryotop® method for vitrification of pronuclear (2PN) stage oocytes within an IVF program? SUMMARY ANSWER: A semi‐automated closed vitrification method gives similar clinical results as compared to an exclusively manual, open system but higher procedure duration and less staff convenience. WHAT IS KNOWN ALREADY: A semi‐automated closed vitrification device has been introduced to the market, however, little evaluation of its performance in a clinical setting has been conducted so far. STUDY DESIGN, SIZE, DURATION: This prospective, randomised, open non‐inferiority trial was conducted at three German IVF centers (10/2017‐12/2018). Randomization was performed on day of fertilization check, stratified by center and by indication for vitrification (surplus 2PN oocytes in the context of a fresh embryo transfer (ET) cycle or 'freeze‐all' of 2PN oocytes). PARTICIPANT/MATERIAL, SETTING, METHODS: The study population included subfertile women, aged 18‐40 years, undergoing IVF or ICSI treatment after ovarian stimulation, with 2PN oocytes available for vitrification. The primary outcome was survival rate of 2PN oocytes at first warming procedure in a subsequent cycle and non‐inferiority of 2PN survival was to be declared if the lower bound 95% CI of the mean difference in survival rate excluded a difference larger than 9.5%; secondary, descriptive outcomes included embryo development, pregnancy and live birth rate, procedure time and staff convenience. MAIN RESULTS AND THE ROLE OF CHANCE: The randomised patient population consisted of 149 patients, and the per‐protocol population (patients with warming of 2PN oocytes for culture and planned ET) was 118 patients. The survival rate was 94.0% (±13.5) and 96.7% (±9.7) in the Gavi® and the Cryotop® group (weighted mean difference ‐1.6%, 95% CI ‐4.7 to 1.4, P = 0.28), respectively, indicating non‐inferiority of the Gavi® vitrification/warming method for the primary outcome. Embryo development and the proportion of top‐quality embryos was similar in the two groups, as were the pregnancy and live birth rate. Mean total procedure duration (vitrification and warming) was higher in the Gavi® group (81 ± 39 min vs 47 ± 15 min, mean difference 34 min, 95% CI 19 to 48). Staff convenience assessed by eight operators in a questionnaire was lower for the Gavi® system. The majority of respondents preferred the Cryotop® method because of practicality issues. LIMITATIONS, REASON FOR CAUTION: The study was performed in centers with long experience of manual vitrification, and the relative performance of the Gavi® system as well as the staff convenience may be higher in settings with less experience in the manual procedure. Financial costs of the two procedures were not measured along the trial. WIDER IMPLICATIONS OF THE FINDINGS: With increasing requirements for standardization of procedures and tissue safety, a semi‐automated closed vitrification method may constitute a suitable alternative technology to the established manual open vitrification method given the equivalent clinical outcomes demonstrated herein. STUDY FUNDING/COMPETING INTERESTS: The trial received no direct financial funding. The Gavi® instrument, Gavi® consumables and staff training were provided for free by the distributor (Merck, Darmstadt, Germany) during the study period. The manufacturer of the Gavi® instrument had no influence on study protocol, study conduct, data analysis, data interpretation or manuscript writing. J.H. has received honoraria and/or non‐financial support from Ferring, Merck and Origio. G.G. has received honoraria and/or non‐financial support from Abbott, Ferring, Finox, Gedeon Richter, Guerbet, Merck, MSD, ObsEva, PregLem, ReprodWissen GmbH and Theramex. The remaining authors have no competing interests. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03287479. TRIAL REGISTRATION DATE: 19 September 2017. A E OF FIRST PATIENT’S ENROLMENT: 10 October 2017.

Hajibandeh, S., et al. (2021). "Meta-analysis of laparoscopic mesh rectopexy versus posterior sutured rectopexy for management of complete rectal prolapse." International Journal of Colorectal Disease 36(7): 1357-1366.
	Objectives: To evaluate comparative outcomes of laparoscopic mesh rectopexy (LMR) and laparoscopic posterior sutured rectopexy (LPSR) in patients with rectal prolapse.; Methods: We conducted a systematic search of electronic databases and bibliographic reference lists with application of a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators, and limits. Recurrence, Cleveland Clinic Incontinence Score (CCIS), Cleveland Clinic Constipation Score (CCCS), surgical site infections, procedure time, and length of hospital stay were the evaluated outcome measures.; Results: We identified 5 comparative studies reporting a total of 307 patients evaluating outcomes of LMR (n=160) or LPSR (n=147) in patients with rectal prolapse. LMR was associated with significantly lower recurrence rate (OR: 0.28, P=0.009) but longer procedure time (MD: 23.93, P<0.0001) compared to LPSR. However, there was no significant difference in CCIS (MD: -1.02, P=0.50), CCCS (MD: -1.54, P=0.47), surgical site infection (OR: 1.48, P=0.71), and length of hospital stay (MD: -1.54, P=0.47) between two groups. No mesh erosion was reported in any of the included studies at maximum follow-up point. Sub-group analyses with respect to ventral mesh rectopexy, posterior mesh rectopexy, randomised studies, and adult patients were consistent with the main analysis.; Conclusions: LMR seems to be associated with lower recurrence but longer procedure time compared to LPSR. Although no mesh-related complications have been reported by the included studies, no definitive conclusions can be made considering that the included studies were inadequately powered for such outcome. Future high-quality randomised studies with adequate sample size are required.

Hajizadeh-Sharafabad, F., et al. (2019). "Selenium and Polycystic Ovary Syndrome; Current Knowledge and Future Directions: A Systematic Review." Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 51(5): 279-287.
	Polycystic ovary syndrome (PCOS), as the most common endocrine disorder in reproductive-aged women, is recognized by hyperandrogenism and insulin resistance. Selenium (Se) potentially possesses therapeutic effects on PCOS due to antioxidant and insulin-like properties. This systematic review evaluates the potential role of Se in the complications of PCOS. A systematic review was performed on published studies reporting the effects of Se on PCOS. Three major databases including PubMed, Scopus, and Google Scholar were searched until December 2018. A total of 7 human studies and two in vitro studies met the inclusion criteria. Two out of three case-control studies showed that serum Se levels tend to decrease in patients with PCOS. Of four studies that evaluated the impact of Se supplementation on insulin resistance, only one study showed protective effects of Se against insulin resistance. Two out of three studies reported the antioxidant effect of Se. Few studies investigating anti-androgenic effect of Se presented controversial results. There were three studies that evaluated the anti-hyperlipidemic effect of Se, of which two surveys indicated the lowering effects of Se on VLDL and LDL-cholesterol. The reviewed studies confirmed inverse relationships between serum Se levels and some androgenic hormones in PCOS. Se is able to attenuate insulin resistance and dyslipidemia. The available data are currently insufficient to support the protective effects of Se on PCOS.; Competing Interests: The authors declare that they have no conflict of interest. (© Georg Thieme Verlag KG Stuttgart · New York.)

Halder, G., et al. (2022). "Cost effectiveness of additional preoperative telephone visit: Analysis of a randomized trial on surgical preparedness." International Urogynecology Journal 33(Supplement 1): S19-S20.
	Introduction: Surgical preparedness improves patient satisfaction and perioperative outcomes. We performed a RCT of a provider-initiated telephone visit in addition to usual preoperative counseling (TELE) versus usual preoperative counseling alone (usual care) and found that a supplemental preoperative telephone visit improved patient surgical preparedness. Objective(s): In this ancillary analysis our objective was to assess the costeffectiveness of a preoperative telephone visit versus usual preoperative counseling alone. Method(s): We performed a planned prospective economic evaluation concurrent with a RCT of 132 women randomized to either TELE (n=63) or usual care (n=69) followed for 8 weeks after surgery for stress urinary incontinence and/or pelvic organ prolapse. A within-trial analysis from the health care sector (HCS) - formal medical costs borne by third-party payers and patients - and societal perspectives (SP) - all costs regardless of who incurs - was performed as recommended by the Second Panel on Cost- Effectiveness in Health and Medicine. Costs are in 2019 U.S. dollars and include medical care, complications, patient and caregiver time, transportation, and lost productivity. A macro-costing approach was used; medical resource use was multiplied by price weights based on national Medicare reimbursement rates or published prices. Effectiveness measures include 1) quality-adjusted life-years (QALYs), calculated from the EuroQol 5D (EQ-5D), and 2) surgical preparedness, measured by the Preoperative Patient Questionnaire; with a response of "strongly agree" to "Overall, I feel prepared for my upcoming surgery." Our primary outcome was the incremental cost effectiveness ratio (ICER) of TELE vs. usual care, defined as the difference between groups in mean cost divided by the difference in mean QALYs (i.e., QALY ICER). A secondary ICER was also calculated using surgical preparedness as the measure of effectiveness (i.e., preparedness ICER). Costs and QALYs were not discounted because of the 8- week analysis time horizon. Result(s): Baseline characteristics and peri-operative course were similar between groups (Table 1). QALYs gained were similar between groups, 0.132 + 0.023for TELE and 0.131 + 0.017 for usual care (p=0.881). The TELE group was more prepared for surgery (83% vs 59%, p<0.05). The cumulative mean per-person cost over 8 weeks was similar between groups from the HCS ($8,707 + 3,278 TELE vs. $8,433 + 3,099 usual care, p=0.623) and SP ($11,119 + 5,105 TELE vs. $11,052 + 4,850 usual care, p=0.938). The preoperative telephone intervention was cost-effective from the SP (ICER = $67,000/QALY) but not from the HCS perspective (ICER = $274,000/QALY) using the generally accepted maximum willingness to pay threshold of $150,000/QALY. The incremental cost per percentage patient surgical preparedness gained was $2.79 from the SP and $11.42 from the HCS. Conclusion(s): A provider-initiated preoperative telephone visit significantly improves patient surgical preparedness and is cost-effective from the SP.

Halder, G. E., et al. (2021). "20 Cost effectiveness of additional preoperative telephone visit: Analysis of a randomized trial on surgical preparedness." American Journal of Obstetrics and Gynecology 224(6 Supplement): S739-S740.
	Objectives: Surgical preparedness improves patient satisfaction and perioperative outcomes. We performed a RCT of a provider-initiated telephone visit in addition to usual preoperative counseling (TELE) versus usual preoperative counseling alone (usual care) and found that a supplemental preoperative telephone visit improved patient surgical preparedness. In this ancillary analysis our objective was to assess the cost-effectiveness of a preoperative telephone visit versus usual preoperative counseling alone. Material(s) and Method(s): We performed a planned prospective economic evaluation concurrent with a RCT of 132 women randomized to either TELE (n = 63) or usual care (n = 69) followed for 8 weeks after surgery for stress urinary incontinence and/or pelvic organ prolapse. A within-trial analysis from the health care sector (HCS) - formal medical costs borne by third-party payers and patients - and societal perspectives (SP) - all costs regardless of who incurs - was performed as recommended by the Second Panel on Cost-Effectiveness in Health and Medicine. Costs are in 2019 U.S. dollars and include medical care, complications, patient and caregiver time, transportation, and lost productivity. A macro-costing approach was used; medical resource use was multiplied by price weights based on national Medicare reimbursement rates or published prices. Effectiveness measures include (1) quality-adjusted life-years (QALYs), calculated from the EuroQol 5D (EQ-5D), and (2) surgical preparedness, measured by the Preoperative Patient Questionnaire; with a response of "strongly agree" to "Overall, I feel prepared for my upcoming surgery." Our primary outcome was the incremental cost effectiveness ratio (ICER) of TELE vs. usual care, defined as the difference between groups in mean cost divided by the difference in mean QALYs (i.e., QALY ICER). A secondary ICER was also calculated using surgical preparedness as the measure of effectiveness (i.e., preparedness ICER). Costs and QALYs were not discounted because of the 8-week analysis time horizon. Result(s): Baseline characteristics and peri-operative course were similar between groups (Table 1). QALYs gained were similar between groups, 0.132 + 0.023 for TELE and 0.131 + 0.017 for usual care (P = 0.881). The TELE group was more prepared for surgery (83% vs 59%, P < 0.05). The cumulative mean per-person cost over 8 weeks was similar between groups from the HCS ($8,707 + 3,278 TELE vs. $8,433 + 3,099 usual care, P = 0.623) and SP ($11,119 + 5,105 TELE vs. $11,052 + 4,850 usual care, P = 0.938). The preoperative telephone intervention was cost-effective from the SP (ICER = $67,000/QALY) but not from the HCS perspective (ICER = $274,000/QALY) using the generally accepted maximum willingness to pay threshold of $150,000/QALY. The incremental cost per percentage patient surgical preparedness gained was $2.79 from the SP and $11.42 from the HCS. Conclusion(s): A provider-initiated preoperative telephone visit significantly improves patient surgical preparedness and is cost-effective from the SP. [Formula presented]Copyright © 2021

Hall, L. M., et al. (2020). "Do features of randomized controlled trials of pelvic floor muscle training for postprostatectomy urinary incontinence differentiate successful from unsuccessful patient outcomes? A systematic review with a series of meta-analyses." Neurourology and Urodynamics 39(2): 533-546.
	AIMS: Efficacy of pelvic floor muscle training (PFMT) for postprostatectomy incontinence (PPI) differs between randomized clinical trials (RCT). This might be explained by variation in content/delivery of PFMT (eg, biofeedback, muscles targeted, and time of commencement of training). This review investigated whether outcome of meta-analysis differs based on presence or not of specific RCT features. METHODS: PubMed, CINAHL, EMBASE, Physiotherapy Evidence Database (PEDro), and Cochrane were searched for RCTs that investigated efficacy of PFMT on PPI. PFMT details and outcomes were extracted. Methodological quality and comprehensiveness of PFMT reporting was assessed using the PEDro scale and Consensus on Reporting Template, respectively. Effect size and 95% confidence intervals were calculated for incontinence rate at 3 months. To identify features that influenced efficacy, separate meta-analyses were performed for studies with and without specific features. RESULTS: Twenty-two trials were included, and 15 were used for meta-analysis of 3-month outcomes. Overall, meta-analysis showed reduced incontinence with PFMT (risk ratio [RR] = 0.85; I2 = 55%; P = .005). Meta-analyses showed better outcomes for PFMT than control groups when the study included preoperative PFMT (RR = 0.76; I2 = 30%; P = .006), biofeedback (RR = 0.73; I2 = 58%; P = .006), instruction to contract around the urethra (RR = 0.9; I2 = 43%; P = .009), a control group without PFMT instruction (RR = 0.85; I2 = 69%; P = .05), inclusion of all men irrespective of continence status (RR = 0.84; I2 = 30%; P = .003) and continence defined as no leakage (RR = 0.85; I2 = 48%; P = .05). CONCLUSIONS: Preoperative PFMT, biofeedback, urethral instructions, no PFMT instruction for controls, inclusion of all men, and continence defined as no leakage are features associated with successful patient outcomes. Future studies should consider these features in design of interventions and pooling data for meta-analysis.

Hamada, M., et al. (2022). "A novel orally active gonadotropin-releasing hormone antagonist, relugolix, is a potential substitute for injectable GnRH antagonists in controlled ovarian stimulation in assisted reproductive technology." Reproductive Medicine and Biology 21(1): e12424.
	Purpose: To evaluate the efficacy of an oral gonadotropin-releasing hormone antagonist (GnRH Ant), relugolix (R), for assisted reproductive technology (ART). Method(s): We enrolled women undergoing ART using a GnRH Ant for controlled ovarian stimulation. We compared R; 20 mg/day with cetrorelix acetate (C); 0.125 mg. C was administered to 88 women in 2019, and R to 93 women in 2020. Clinical outcomes associated with ART were assessed in both groups. Result(s): The luteinizing hormone levels on the day of human chorionic gonadotropin injection in the R group (1.26 +/- 0.93 IU/L) were significantly lower than those in the C group (2.85 +/- 3.02 IU/L). There were no cases in which egg retrieval was canceled in both groups. The total doses of gonadotropins administered were greater in the R group compared with the C group. The number of days of GnRH Ant administration in the R group (1.71 +/- 0.57 days) was significantly longer compared with the C group (1.48 +/- 0.58 days). The number of oocytes collected, fertilization rates, and pregnancy rates (R; 47.1% vs C; 45.8%) did not differ between the two groups. Conclusion(s): An orally active GnRH Ant, relugolix, when used in controlled ovarian stimulation for ART, showed comparable clinical outcomes with cetrorelix.Copyright © 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

Hamdaoui, N., et al. (2021). "Pain Associated With Cervical Priming for First-Trimester Surgical Abortion: a Randomized Controlled Trial." Obstetrics and Gynecology 137(6): 1055‐1060.
	OBJECTIVE: To compare the effect of cervical priming with mifepristone with that of misoprostol on pain perception during surgical induced abortion under paracervical block. METHODS: We conducted a randomized, single‐blind, two‐center study of women undergoing surgical induced abortion at less than 14 weeks of gestation under paracervical block. Participants were randomized to receive cervical priming with 200 mg of oral mifepristone 36 hours or 400 micrograms buccal misoprostol 3 hours before surgery. The primary outcome was pain during mechanical cervical dilation evaluated by a 100‐mm visual analog scale (VAS). Secondary outcomes were pain during aspiration, preoperative and postoperative pain, participant satisfaction, duration of the procedure, occurrence of complications, and ease of performing the procedure (assessed by a 100‐mm VAS). We estimated that 110 women would have to be included to have 90% power to detect a 13mm‐difference of VAS for pain. RESULTS: Between June 2017 and May 2019, 314 women were eligible and 110 were randomized (55 in each group). Patient characteristics were similar in the two groups. The mean VAS score during mechanical cervical dilation was lower in the mifepristone group (35.6±21 vs 43.5±21, P=.04) as was the mean VAS during aspiration (34±24 vs 47.8±23, P=.003). The preoperative and postoperative mean VAS, satisfaction and duration of procedures were similar between groups. The procedure was significantly easier to perform in the mifepristone group (88±16 vs 80±23, P=.004). CONCLUSION: Cervical priming with mifepristone for surgical induced abortion under paracervical block up to 14 weeks of gestation is more effective than misoprostol in reducing pain perception. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03043014.

Hameed, R. H. (2019). "VTE risk in postmenopausal women receiving oral and non-oral hormone therapy systematic review and meta-analysis." Indian journal of forensic medicine and toxicology 13(1): 302-306.
	Hormone replacement therapy can improve the quality of life for women with hypo-oestrogenic symptoms. Many women are still prescribed oestrogen therapy to treat postmenopausal symptoms. Venous thromboembolism (VTE), either deep vein thrombosis or pulmonary embolism, is a main harmful effect of HT among postmenopausal women. We aim to evaluate the risk of VTE in postmenopausal women using hormonal therapy either oral or non-oral types. Systematic review of MEDLINE, Cochrane CENTRAL, EMBASE, and ClinicalTrials.gov according to PRISMA guidelines. 22 studies were included in the metaanalyses (9 case-control studies, 9 cohort studies, and 4 randomized controlled trials). VTE risk was not increased with non-oral HT, including users of estrogens and estrogens plus progestins (OR 0.97 [0.9-1.06]), non-oral estrogen therapy (ET)-only (OR 0.95 [0.81-1.10]), and non-oral combined estrogen-progestin therapy (OR 0.92 [0.77-1.09]). The comparison of non-oral vs. oral HT showed increased VTE risk with oral HT (OR 1.66 [1.39-1.98]). Increase the risk of VTE in postmenopausal women who using oral HT versus non oral HT.Copyright © 2019, Indian Journal of Forensic Medicine and Toxicology. All rights reserved.

Hamid, O., et al. (2022). "First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors." Journal for Immunotherapy of Cancer 10(10).
	Background: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors.; Methods: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every 4 weeks (Q4W)) intravenously. Dose-expansion: patients with melanoma (n=10) and NSCLC (n=20) who progressed on prior anti-programmed death receptor 1/programmed death ligand-1 and/or anti-cytotoxic T-lymphocyte-associated antigen 4 (melanoma) received ivuxolimab 30 mg Q2W intravenously plus utomilumab 20 mg Q4W intravenously. Adverse events (AEs) were graded per National Cancer Institute Common Terminology Criteria for Adverse Events V.4.03 and efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and immune-related RECIST (irRECIST). Paired tumor biopsies and whole blood were collected to assess pharmacodynamic effects and immunophenotyping. Whole blood samples were collected longitudinally for immunophenotyping.; Results: Dose-escalation: 57 patients were enrolled; 2 (3.5%) patients with melanoma (0.3 mg/kg+20 mg and 0.3 mg/kg+100 mg) achieved partial response (PR), 18 (31.6%) patients achieved stable disease (SD); the disease control rate (DCR) was 35.1% across all dose levels. Dose-expansion: 30 patients were enrolled; 1 patient with NSCLC achieved PR lasting &gt;77 weeks. Seven of 10 patients with melanoma (70%) and 7 of 20 patients with NSCLC (35%) achieved SD: median (range) duration of SD was 18.9 (13.9-49.0) weeks for the melanoma cohort versus 24.1 (14.3-77.9+) weeks for the NSCLC cohort; DCR (NSCLC) was 40%. Grade 3-4 treatment-emergent AEs were reported in 28 (49.1%) patients versus 11 (36.7%) patients in dose-escalation and dose-expansion, respectively. There were no grade 5 AEs deemed attributable to treatment. Ivuxolimab area under the concentration-time curve increased in a dose-dependent manner at 0.3-3 mg/kg doses.; Conclusions: Ivuxolimab+utomilumab was found to be well tolerated and demonstrated preliminary antitumor activity in selected groups of patients.; Trial Registration Number: NCT02315066.; Competing Interests: Competing interests: OH reports consulting fees from Aduro, Akeso, Amgen, Beigene, Bioatia, Bristol Myers Squibb, Roche Genentech, GlaxoSmithKline, Immunocore, Idera, Incyte, Janssen, Merck, Nextcure, Novartis, Pfizer, Sanofi Regeneron, SeaGen, Tempus, and Zelluna; honoraria for speaker bureaus from Bristol Myers Squibb, Novartis, Pfizer, and Sanofi Regeneron; and participation on a data safety monitoring board or advisory board for Aduro, Akeso, Amgen, Beigene, Bioatia, Bristol Myers Squibb, Roche Genentech, GlaxoSmithKline, Immunocore, Idera, Incyte, Janssen, Merck, Nextcure, Novartis, Pfizer, Sanofi Regeneron, SeaGen, Tempus, and Zelluna. AAC reports grants or contracts from AstraZeneca and Bristol Myers Squibb; consulting fees from Jazz, Janssen, and Pfizer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, Blueprint, Genentech, Merck, Novartis, and Takeda; and participation on a data safety monitoring board or advisory board for AstraZeneca, Bristol Myers Squibb, Ipsen, and Novartis. JAT reports grants or contracts from Pfizer. TD reports grants or contracts to his institution from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, IQVIA, Janssen Pharma, Merck Serono, MSD, Novartis, Pfizer, Sumitomo Dainippon, and Ta ho; consulting fees from AbbVie, Bayer, Chugai Pharma, Otuska Pharma, Rakuten Medical, Sumitomo Dainippon, Taiho, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol Myers Squibb, Oncolys Bio Pharma, Ono Pharma, Rakuten Medical, and Taiho; and participation on a data safety monitoring board or advisory board for AbbVie, Amgen, Astellas Pharma, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Janssen Pharma, MSD, and Novartis. SH-L reports consulting fees from Amgen, Astellas, Bristol Myers Squibb, Genmab, Merck, Regeneron, and Xencor; and research grants from Astellas, Boehringer Ingelheim, Checkmate, Dragonfly, F Star, Kite Pharma, Merck, OncoC4, Vedanta, and Xencor. AD reports grants or contracts from Apexigen, Idera, and Nektar; and consulting fees from Idera and Nektar. J-PS reports consulting fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sakyo, Gilead, GlaxoSmithKline, LeoPharma, Eli Lilly, MSD, Mylan, Novartis, Pierre Fabre Oncology, Pfizer, Roche Genentech; and support for attending meetings and/or travel from Amgen, AstraZeneca, and Pfizer. NR reports research grants from Pfizer; personal fees from AbbVie, Apricity Therapeutics, AstraZeneca, Bellicum Pharmaceuticals, Boehringer Ingelheim, Brooklyn ImmunoTherapeutics, Calithera Biosciences, Dracen Pharmaceuticals, Editas Medicine, Eli Lilly and Company, EMD Serono Inc, G1 Therapeutics, Genentech, Gilead Sciences, GlaxoSmithKline, Gritstone Bio, Illumina, Merck, Neogenomics Laboratories, Novartis, Takeda Pharmaceutical Company, and Synthekine; and royalties related to a patent filed by Memorial Sloan Kettering Cancer Center: determinants of cancer response to immunotherapy, (PCT/US2015/062208) licensed to Personal Genome Diagnostics. EA reports consulting fees from Celgene Research, GlaxoSmithKline, MedImmune, and Merck Sharp & Dohme; and support for attending meetings and/or travel from AbbVie, MedImmune, Pfizer, Roche, and Sanofi. ABE-K reports personal fees from Agenus, ABL Bio, Bayer, BMS, Exelixis, Eisai, and AstraZeneca; grants and personal fees from Astex, Pieris, Cytomx, Gilead, EMD Serono, Roche/Genentech, and Merck; and grants from Fulgent outside the submitted work. PAO reports grants or contracts from Amgen, Armo BioSciences, Array, AstraZeneca/MedImmune, Bristol Myers Squibb, Celldex, CytomX, Merck, Neon Therapeutics, Novartis, Oncorus, Pfizer, Roche Genentech, and Xencor; consulting fees from Array, Merck, Bristol Myers Squibb, Evaxion, and Novartis; and participation on a data safety monitoring board or advisory board for Array, Merck, Bristol Myers Squibb and Novartis. FALME, WR, and JSW have nothing to disclose. JC and AF were employees of Pfizer at the time of the study and hold stock or stock options in Pfizer. CG and WY are employees of Pfizer and hold stock or stock options in Pfizer. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hamilton, J., et al. (2021). "A randomized, controlled pilot study of cognitive analytic therapy for stressed pregnant women with underlying anxiety and depression in a routine health service setting." Clinical Psychology & Psychotherapy 28(2): 394-408.
	A pilot study of cognitive analytic therapy (CAT) plus treatment as usual (TAU), versus TAU in stressed pregnant women with anxiety and depression, was undertaken as an essential preliminary to any definitive, randomized controlled trial (RCT). The trial was pragmatic, multicentre, parallel, randomized, controlled, and unblinded. Participants were pregnant women screened using the Hospital Anxiety and Depression Scale (HADS). Treatment was standard 16-session CAT. Main outcome measures were Spielberger State/Trait Anxiety Inventory (STAI) (primary outcome measure) at 24 weeks after randomization, therefore 1 month after therapy for the CAT group; HADS; Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM); Edinburgh Postnatal Depression Scale (EPDS); 36-item Short Form Health Survey (SF-36); and a brief Experiences of Therapy Questionnaire, completed at baseline and on average at 12, 24, 40, and 82 weeks after randomization. Thirty-nine patients (CAT + TAU, n = 20; TAU, n = 19) were randomized with mean baseline STAI State scores of 50.8 (SD 11.4) and 51.1 (SD 13.3), respectively. Sixteen patients had missing primary outcome data leaving 23 (n = 11 and n = 12) patients for analysis. The mean STAI State score was 38.5 (SD 13.8) and 45.7 (SD 16.8) in the CAT and TAU groups respectively at 24 weeks after randomization, with an adjusted difference in means of 7.2 (95% confidence interval [CI]: -7.9 to 20.6). No safety issues were reported. Patient retention for the CAT group was high (18/20; 90% of patients completed therapy). Ten out of 11 (90.9%) respondents 'agreed' or 'strongly agreed' that having CAT had been 'very helpful'. The study demonstrated the feasibility of safely undertaking CAT in this setting. Outcomes showed positive trends compatible with a clinically important effect, although statistically definitive conclusions cannot be drawn in such a study.

Hamilton Kacey, M., et al. (2023). "Surgical management of endometriosis to optimize fertility." Current opinion in obstetrics & gynecology 35(4): 389-394.
	Purpose of Review: Surgery is an integral element of treatment for infertility caused by endometriosis. This review summarizes the purported mechanisms of infertility in endometriosis, as well as the impacts of surgery for endometriosis on fertility, including pregnancy achieved spontaneously and with assisted reproductive technology (ART).; Recent Findings: Endometriosis' effect on fertility is multifactorial. The sequela of increased inflammation resulting from endometriosis causes alterations in ovarian, tubal, and uterine function. Removing or destroying these lesions reduces inflammation. Surgical treatment of both early-stage endometriosis and deeply infiltrating endometriosis improves spontaneous pregnancy rates and ART pregnancy rates. Conventional or robotic laparoscopy is the preferred surgical approach.; Summary: Endometriosis has detrimental effects on fertility, including negative impacts on oocyte, tubal, and endometrial function. Laparoscopic surgery for endometriosis elevates both spontaneous and ART pregnancy rates above those achieved with expectant management alone. The resection or destruction of endometriosis implants reduces inflammation, which likely improves the multifactorial infertility related to endometriosis. This topic is complex and controversial; more research in the form of high-quality randomized control trials is needed. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hammoud, D., et al. (2020). "Comparative efficacy of first-line maintenance PARP inhibitors (PARPI) in advanced ovarian cancer (OC): A network meta-analysis." Ann. Oncol. 31: S623-None.
	
Hamoda, H. and A. Sharma (2024). "Premature ovarian insufficiency, early menopause, and induced menopause." Best practice & research. Clinical endocrinology & metabolism 38(1): 101823.
	Premature ovarian insufficiency (POI) is a condition in which there is a decline in ovarian function in women who are younger than 40 years resulting in a hypo-oestrogenic state with elevated gonadotrophins and oligomenorrhoea/amenorrhoea. This leads to short term complications of menopausal symptoms and long-term effects on bone and cardiovascular health, cognition as well as the impact of reduced fertility and sexual function associated with this condition. It is managed by sex steroid replacement either with HRT or combined hormonal contraception until the age of natural menopause (51) and this can provide a beneficial role with both symptom control and minimising the long-term adverse effects associated with this condition. Women who undergo a menopause between 40 and 45 years are deemed to have an "early menopause". The limited data available for this group suggest that they also have an increased morbidity if not adequately treated with hormone therapy. As such, women who have an early menopause should be managed in a similar way to those with POI, with the recommendation that they should take HRT at least until the natural age of menopause. This is the same for induced menopause that is caused by medical or surgical treatment that impacts the ovaries. It is important to ensure early diagnosis and access to specialist care to help support and manage these patients to reduce the symptoms and risks of long-term complications. This review looks at the diagnosis, causes, short and long-term complications and management of POI, early and induced menopause. (Copyright © 2023. Published by Elsevier Ltd.)

Hamulyak, E. N., et al. (2021). "Heavy menstrual bleeding on direct factor Xa inhibitors: rationale and design of the MEDEA study." Research and practice in thrombosis and haemostasis 5(1): 223‐230.
	Background: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. Rationale and Design: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant‐associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open‐label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. Outcomes: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study.

Hamulyák Eva, N., et al. (2021). "Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome-What is the evidence?" Journal of thrombosis and haemostasis : JTH 19(5): 1174-1185.
	Aspirin and heparin are widely used to reduce the risk of recurrent pregnancy loss in women with antiphospholipid syndrome. This practice is based on only a few intervention studies, and uncertainty regarding benefits and risk remains. In this case-based review, we summarize the available evidence and address the questions that are most important for clinical practice. We performed a systematic review of randomized controlled trials assessing the effect of heparin (low molecular weight heparin [LMWH] or unfractionated heparin [UFH]), aspirin, or both on live birth rates in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Eleven trials including 1672 women met the inclusion criteria. Aspirin only did not increase live birth rate compared to placebo in one trial of 40 women (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.71-1.25). One trial of 141 women reported a higher live birth rate with LMWH only than with aspirin only (RR 1.20; 95% CI 1.00-1.43). Five trials totaling 1295 women compared heparin plus aspirin with aspirin only. The pooled RR for live birth was 1.27 (95% CI 1.09-1.49) in favor of heparin plus aspirin. There was significant heterogeneity between the subgroups of LMWH and UFH (RR for LWMH plus aspirin versus aspirin 1.20, 95% CI: 1.04-1.38; RR for UFH plus aspirin versus aspirin 1.74, 95% CI: 1.28-2.35; I 2 78.9%, p = .03). Characteristics of participants and adverse events were not uniformly reported. Heparin (LMWH or UFH) plus aspirin may improve live birth rates in women with recurrent pregnancy loss and antiphospholipid antibodies, but evidence is of low certainty. (© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Han, A. and H. Kim Tae (2023). "Effects of self-compassion interventions on reducing depressive symptoms, anxiety, and stress: A meta-analysis." Mindfulness: 1-29.
	Objectives A growing body of evidence shows self-compassion can play a key role in alleviating depressive symptoms, anxiety, and stress in various populations. Interventions fostering self-compassion have recently received increased attention. This meta-analysis aimed to identify studies that measured effects of self-compassion focused interventions on reducing depressive symptoms, anxiety, and stress.MethodsA comprehensive search was conducted within four databases to identify relevant randomized controlled trials (RCTs). The quality of the included RCTs was assessed using the Cochrane Collaboration risk-of-bias tool. Either a random-effects model or fixed-effects model was used. Subgroup analyses were conducted according to types of control groups, intervention delivery modes, and the involvement of directly targeted populations with psychological distress symptoms.ResultsFifty-six RCTs met the eligibility criteria. Meta-analyses showed self-compassion focused interventions had small to medium effects on reducing depressive symptoms, anxiety, and stress at the immediate posttest and small effects on reducing depressive symptoms and stress at follow-up compared to control conditions. The overall risk of bias across included RCTs was high.ConclusionsFewer studies were conducted to compare effects of self-compassion interventions to active control conditions. Also, fewer studies involved online self-compassion interventions than in-person interventions and directly targeted people with distress symptoms. Further high-quality studies are needed to verify effects of self-compassion interventions on depressive symptoms, anxiety, and stress. As more studies are implemented, future meta-analyses of self-compassion interventions may consider conducting subgroup analyses according to intervention doses, specific self-compassion intervention techniques involved, and specific comparison or control groups.PreregistrationThis study is not preregistered. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Han, A. and T. H. Kim (2022). "Efficacy of Internet-Based Acceptance and Commitment Therapy for Depressive Symptoms, Anxiety, Stress, Psychological Distress, and Quality of Life: Systematic Review and Meta-analysis." Journal of Medical Internet Research 24(12): e39727.
	BACKGROUND: Acceptance and commitment therapy (ACT) is an empirically supported transdiagnostic approach that involves mindfulness processes and behavior change processes for valued living. OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the efficacy of internet-based ACT (iACT) for depressive symptoms, anxiety, stress, psychological distress, and quality of life (QoL). METHODS: PubMed, CINAHL, PsycINFO, and SCOPUS databases were searched to identify relevant RCTs published up to June 5, 2021. The included RCTs were assessed using the Cochrane Collaboration risk-of-bias tool. The use of either a random effects model or fixed effects model was determined using I2 statistic values for heterogeneity. Subgroup analyses were conducted according to the type of control group, the use of therapist guidance, delivery modes, and the use of targeted participants, when applicable. RESULTS: A total of 39 RCTs met the inclusion criteria. Meta-analyses found small effects of iACT on depressive symptoms, anxiety, stress, psychological distress, and QoL at the immediate posttest and follow-up. There was no significant effect of iACT on stress at follow-up. Subgroup analyses showed small to medium effects of iACT on all the outcomes at the immediate posttest and follow-up compared with the passive control groups. In contrast, subgroup analyses that compared iACT with active control groups found no differences between groups on stress, psychological distress, and QoL at the immediate posttest or on depressive symptoms, anxiety, and stress at follow-up. In addition, subgroup analyses conducted according to the use of therapist guidance, delivery modes, and the use of targeted participants found no statistically significant subgroup differences among studies in all the outcomes, except for the subgroup difference among studies according to the use of targeted participants for depressive symptoms at the immediate posttest (ie, a statistically significant, larger effect of iACT when studies targeted people with depressive symptoms). The overall risk of bias across the studies was unclear. CONCLUSIONS: The findings of this study contribute to the body of evidence regarding the effects of iACT on depressive symptoms, anxiety, stress, psychological distress, and QoL and may be applicable in any population, as ACT is a transdiagnostic approach. Few studies have compared iACT with active control conditions, especially for stress and psychological distress at the immediate posttest and follow-up. In addition, the active control conditions varied among the included studies. Further high-quality studies are needed to better understand whether iACT is comparable or superior to other evidence-based interventions, such as cognitive behavioral therapy, in decreasing depressive symptoms, anxiety, stress, and psychological distress and improving QoL.

Han, B., et al. (2021). "Observation on the effect of self-made Yishen Zhuyu Decoction on uterine involution after artificial abortion." 广西中医药 44(1): 21‐23.
	Objective: To observe the effect of self‐made Yishen Zhuyu Decoction on uterine involution after artificial abortion. Methods: 90 patients after induced abortion were randomly divided into the experimental group of 45 cases and the control group of 45 cases. Results: The postoperative vaginal bleeding time in the experimental group was shorter than that in the control group, and the endometrial thickness and the time of the first menstrual cramp in the experimental group were better than those in the control group. Conclusion: Self‐made Yishen Zhuyu Decoction is beneficial to uterine involution after induced abortion.

Han, E. J., et al. (2022). "Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(6): 2197-2202.
	This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively ( p = .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p = .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact Statement What is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran ® ; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient. What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran. What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

Han, J. (2021). "Comparison of clinical efficacy of painless induced abortion with visualized and painless induced abortion under B ultrasonography." 医药前沿 11(26): 10‐12.
	Objective: To compare the effect of B‐ultrasound surveillance and visual abortion in women undergoing painless induced abortion. Methods: Selected 520 cases of painless artificial abortion who were admitted to our hospital from January 2019 to January 2021, and divided them into routine group (260 cases) and experimental group (260 cases) by random number table method, and the routine group was selected. Painless abortion was monitored by B‐ultrasound, and painless abortion could be seen in the experimental group. The clinical indicators, second uterine clearance rate and postoperative intrauterine adhesion rate were compared between the two groups. Results: The operation time, the duration of vaginal bleeding after operation and the first menstrual rehydration time after operation in the experimental group were shorter than those in the conventional group, and the amount of bleeding during the operation was lower than that in the conventional group (P<0.05). The rate of secondary uterine removal in the experimental group and the routine group were 1.15% and 4.62%, respectively, and the rates of intrauterine adhesion were 1.15% and 4.23%, respectively. The experimental group was lower than the routine group (P<0.05). CONCLUSION: Compared with painless abortion under B‐ultrasound monitoring, visual abortion for women undergoing painless induced abortion can shorten the operation time and postoperative recovery time, reduce intraoperative blood loss, and reduce the rate of secondary uterine removal. and intrauterine adhesions.

Han, J., et al. (2023). "Pregnancy outcome of intravenous immunoglobulin in women with recurrent pregnancy loss." Journal of Reproductive Immunology 156: 103847.
	Purpose: The objective of this study was first to compare the treatment outcome of recurrent pregnancy loss (RPL) women who received intravenous immunoglobulin (IVIG) treatment due to abnormal cellular immunity. We aimed to confirm the effect of IVIG in each subgroup of abnormal cellular immunity. Moreover, while our previously set cut-off value of NK(natural killer) cell level is 16.1%, in Korea, 12% is the widely used cut-off value. We, therefore, aimed to verify the adequacy of treating the patients in the "grey zone" (12-16%). Method(s): RPL was defined as women with 2 or more spontaneous abortions and in total, 987 RPL women visited our clinic from January 2007 to December 2020. Only those with a full evaluation and known treatment outcome were included. A total 204 idiopathic RPL and 209 RPL women with known etiology were enrolled. We investigated the pregnancy outcome by sorting the patients into 7 groups depending on abnormal cellular immunity including NK cell level, NK cell cytotoxicity and TNF-alpha/IL-10 ratio. Then, to verify the cut-off value(16.1%) of NK cell level which we set in our previous study, 152 patients were classified into three groups according to their NK cell level: 1) <12%(low), 2) 12-16%(moderate), 3) >16%(high). Result(s): Among all RPL women with at least one abnormal cellular immunity were treated with IVIG and the overall live birth rate (LBR) was 80.2%. The group which did not have IVIG treatment showed an overall LBR of 78.0%. Within the seven groups with abnormal cellular immunity, the group with both high NK cell cytoxicity and TNF-alpha/IL-10 ratio showed the highest LBR, 100% of LBR and the group with both high NK cell level and TNF-alpha/IL-10 ratio showed the lowest treatment outcome, 71.4%. The live birth rate according low, moderate, and high level of NK cells were 81.0%, 72.5%, and 76.9%. Conclusion(s): IVIG treatment can increase the live birth rate of RPL women with abnormal cellular immunity. The study may provide evidence in selecting RPL patients with immune abnormalities to be treated with IVIG and raise their pregnancy outcomes. Keywords: Recurrent pregnancy loss, abnormal cellular immunity, natural killer cellCopyright © 2023

Han, K., et al. (2022). "A Phase II Randomized Trial of Chemoradiation with or without Metformin in Locally Advanced Cervical Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 28(24): 5263-5271.
	Purpose: Tumor hypoxia is associated with poor response to radiation (RT). We previously discovered a novel mechanism of metformin: enhancing tumor RT response by decreasing tumor hypoxia. We hypothesized that metformin would decrease tumor hypoxia and improve cervical cancer response to RT.; Patients and Methods: A window-of-opportunity, phase II randomized trial was performed in stage IB-IVA cervical cancer. Patients underwent screening positron emission tomography (PET) imaging with hypoxia tracer fluoroazomycin arabinoside (FAZA). Only patients with FAZA uptake (hypoxic tumor) were included and randomized 2:1 to receive metformin in combination with chemoRT or chemoRT alone. A second FAZA-PET/CT scan was performed after 1 week of metformin or no intervention (control). The primary endpoint was a change in fractional hypoxic volume (FHV) between FAZA-PET scans, compared using the Wilcoxon signed-rank test. The study was closed early due to FAZA availability and the COVID-19 pandemic.; Results: Of the 20 consented patients, 6 were excluded due to no FAZA uptake and 1 withdrew. FHV of 10 patients in the metformin arm decreased by an average of 10.2% (44.4%-34.2%) ± SD 16.9% after 1 week of metformin, compared with an average increase of 4.7% (29.1%-33.8%) ± 11.5% for the 3 controls (P = 0.027). Those with FHV reduction after metformin had significantly lower MATE2 expression. With a median follow-up of 2.8 years, the 2-year disease-free survival was 67% for the metformin arm versus 33% for controls (P = 0.09).; Conclusions: Metformin decreased cervical tumor hypoxia in this trial that selected for patients with hypoxic tumor. See related commentary by Lyng et al., p. 5233. (©2022 American Association for Cancer Research.)

Han, L., et al. (2022). "Clinical outcome of lymphadenectomy in malignant ovarian germ cell tumors: a systematic review and meta-analysis." American journal of cancer research 12(9): 4458-4467.
	Malignant ovarian germ cell tumors (MOGCTs) are predominately diagnosed in young patients and account for most preadolescent malignant ovarian tumors. Currently, due to the high sensitivity of MOGCTs to chemotherapy and the optimal survival rate after chemotherapy, some researchers have recommended opting for non-surgical treatment. However, the effect of lymphadenectomy (LND) on the survival of patients with MOGCT remains controversial. We conducted a systematic review and meta-analysis to compare the clinical outcomes of LND and non-LND in MOGCT surgeries in order to summarize the clinical experience. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to December 26, 2021. Data on the rates of survival, relapse, and adverse effects were evaluated using Review Manager software. Fourteen studies with 10,759 participants were included in this review. There were 5863 and 4896 patients in the LND- and LND+ groups, respectively. Pooled results showed that although disease-free survival (DFS) was significantly improved in the LND+ group compared to the LND- group (HR: 0.74; 95% CI: 0.56 to 0.97; 2091 participants), LND did not significantly affect overall survival (OS) (HR: 0.82; 95% CI: 0.51 to 1.31; 5298 participants). The operation time was significantly longer in the LND+ group than in the LND- group (P<0.001). Blood loss (P=0.004) and complication rate (P=0.003) were also significantly higher in the LND+ group than in the LND- group. There was no significant difference in mortality rate (P=0.500). LND was associated with an improvement in DFS. However, there was no significant difference in OS in MOGCTs. We recommend that LND should not be a routine surgery for children or young patients with MOGCTs; although it may be beneficial for older people, advanced stage tumors, specific pathological types, and non-chemotherapy patients.; Competing Interests: None. (AJCR Copyright © 2022.)

Han, L., et al. (2023). "Effect of preoperative cervical conization before hysterectomy on survival and recurrence of patients with cervical cancer: A systematic review and meta-analysis." Gynecologic Oncology 174: 167-174.
	Objective: Conization plays a therapeutic and diagnostic role in cervical cancer. We conducted a systematic review and meta-analysis to compare the clinical outcomes of patients with cervical cancer who underwent hysterectomy with versus without preoperative cervical conization.; Methods: In this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to May 1, 2022.; Results: Eleven studies with 4184 participants were included in this review. There were 2122 patients in the preoperative conization group and 2062 patients in the non-conization group. The meta-analysis showed that disease free survival (DFS) (hazard ratio [HR]: 0.23; 95% CI: 0.12-0.44; 1616 participants; P = 0.030) and overall survival (OS) (HR: 0.54; 95% CI: 0.33-0.86; 1835 participants; P = 0.597) were improved in the preoperative conization group compared with those in the non-conization group. The risk for recurrence was lower in the preoperative conization group than in the non-conization group (odds ratio [OR]: 0.29; 95% CI: 0.17-0.48; 1099 participants; P = 0.434). There was no significant statistical difference regarding intraoperative adverse events (OR: 0.81; 95% CI: 0.18-3.70; 530 participants; P = 0.555) and postoperative adverse events (OR: 1.24; 95% CI: 0.54-2.85; 530 participants; P = 0.170) between the preoperative conization group and non-conization group. In subgroup analysis, patients who benefited more from preoperative conization, had underwent minimally invasive surgery, had smaller local tumor lesions, and had no lymph node involvement.; Conclusions: Preoperative conization before radical hysterectomy may have a protective effect in the treatment of early cervical cancer, with better survival and less recurrence, especially when the patient is at an early stage and undergoes minimally invasive surgery.; Competing Interests: Declaration of Competing Interest The author declares no conflict of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Han, L., et al. (2023). "Minimally invasive versus abdominal radical trachelectomy for early-stage cervical cancer: a systematic review and meta-analysis." American journal of cancer research 13(9): 4466-4477.
	The safety of minimally invasive surgery (MIS) for cervical cancer has been questioned. This systematic review and meta-analysis aimed to compare the clinical outcomes of patients with cervical cancer who underwent MIS and abdominal trachelectomy. We searched for and subsequently analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and Clinical Trials.gov from their inception until April 10, 2023. Six studies with 1,079 participants were included, constituting 512 and 567 patients in the MIS and abdominal surgery groups, respectively. No significant difference was observed in the overall survival (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.16-1.65; I 2 =0.0%; P=0.881), recurrence rate (RR, 1.26; 95% CI, 0.68-2.33; I 2 =0.0%; P=0.815), and death rate (RR, 0.54; 95% CI, 0.23-1.31; I 2 =0.0%; P=0.680) between the MIS and abdominal surgery groups. No significant difference was found in urinary tract complication (RR, 0.78; 95% CI, 0.28-2.17; I 2 =0.0%; P=0.603), cerclage erosion (RR, 0.90; 95% CI, 0.34-2.43; I 2 =0.0%; P=0.650), or cervical stenosis (RR, 0.69; 95% CI, 0.22-2.18; I 2 =0.0%; P=0.885) between both groups. However, significant differences in blood loss and length of hospital stay were observed between both groups. Among 49 females who attempted to get pregnant, 31.3% (5/16) and 51.5% (17/33) in the MIS and abdominal surgery groups, respectively, succeeded in conceiving. We established that laparoscopic and abdominal radical trachelectomy had similar efficacies for treating patients with early cervical cancer, with no significant differences in survival, tumor recurrence, and mortality rates. Additionally, they showed no significant differences in pregnancy-related outcomes. However, owing to the limited number of studies, more high-quality cohort studies are required to confirm these findings.; Competing Interests: None. (AJCR Copyright © 2023.)

Han, L., et al. (2021). "Effect evaluation of sterile distilled water in the nursing process of patients with abdominal incision endometriosis." Indian journal of pharmaceutical sciences 82: 78‐82.
	Han et al.: Evaluation of sterile distilled water in patients with abdominal incision endometriosis To explore the value of sterile distilled water in the care of patients with endometriosis in abdominal wall incision.120 patients who underwent cesarean section under combined lumbar and rigid anesthesia in our hospital from August 2017 to January 2018 were selected as study subjects, and all patients were treated surgically, and were randomly divided into three experimental groups according to their nursing treatment after surgery, control group I (n=40): using saline rinse; control group II (n=40): using 0.5 % povidone‐iodine rinse; experimental Group (n=40): sterile distilled water rinses were used. Observation and comparison of patients' pain status before and after care, quality of life after care and satisfaction with care and the occurrence of complications. The pain and quality of life scores of the three groups of patients before nursing were not significantly different, and after nursing, the pain of patients in all groups was reduced, and the pain and quality of life of patients in the control II group and the test group were significantly reduced compared with the control I group (p<0.05), and there was a significant difference in the quality of life comparison between the control II group and the experimental group (p<0.05), while the difference in pain was not statistically significant (p>0.05). After care, the satisfaction of patients in the control II group and the test group was significantly higher (p<0.05) compared to the control I group, and the test group had the highest satisfaction, but the difference between the control II group and the experimental group was not statistically significant (p>0.05). Compared with the control I group, patients in the control II and test groups had significantly lower complication rates, but the difference between the control II and experimental groups was not statistically significant (p>0.05). The application of sterile distilled water rinsing in the care of patients with abdominal wall incision endometriosis can reduce the pain and alleviate the suffering of patients, while also effectively preventing complications and helping to shorten the recovery process.

Han, Q.-W., et al. (2020). "Efficacy of clomifene citrate for the treatment of patients with polycystic ovary syndrome: A protocol of systematic review." Medicine 99(25): e20590.
	Background: This study aims to assess the efficacy and safety of clomifene citrate (CC) for the treatment of patients with polycystic ovary syndrome (PCOS).; Methods: In this study, we will comprehensively search MEDLINE, EMBASE, The Cochrane Library, Web of Science, CINAHL, ACMD, PsycINFO, and China National Knowledge Infrastructure for original articles published from their inceptions to the January 1, 2020 without language restrictions. All studies will undergo relevance and a design selecting process. Data from qualified studies will be collected by 2 independent authors. Additionally, we will conduct a risk of bias evaluation using a Cochrane risk of bias tool. We will undertake statistical analysis utilizing RevMan 5.3 software.; Results: This study will summarize the up-to-date evidence to investigate the efficacy and safety of CC for the treatment of patients with PCOS.; Conclusion: The findings of this study will provide helpful evidence of CC for the treatment of patients with PCOS, as well as may help develop treatment guidelines.; Prospero Registration Number: PROSPERO CRD42020162818.

Han, S., et al. (2023). "Effectiveness and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a systematic review and meta-analysis." Frontiers in Pharmacology 14: 1330877.
	Background: Studies in recent years have shown that PD-1/PD-L1 inhibitors may have better effectiveness in patients with advanced or recurrent endometrial cancer. The effectiveness of PD-1/PD-L1 inhibitors is thought to be related to mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) classification in advanced or recurrent endometrial cancer. This study aims to evaluate the effectiveness of PD-1/PD-L1 inhibitors in patients classified as dMMR and pMMR. Methods: Medical databases were searched to identify relevant publications up to 30 November 2022. The primary outcome was comparison of objective response rate (ORR) in patients with dMMR and pMMR following treatment with PD-1/PD-L1 inhibitors; secondary outcomes were single-group ORR in patients with dMMR and in patients with pMMR, respectively. Results: Eleven studies were eligible for analysis and patients with advanced or recurrent endometrial cancer with molecular classification of dMMR had a higher total ORR than those with pMMR [odds ratio (OR), 7.70; 95% confidence interval (CI), 3.22-18.38; p < 0.01], with low evidence of between-study heterogeneity (I 2 = 0%). The total ORR of patients with advanced or recurrent endometrial cancer with molecular type dMMR was 51.9% (95% CI, 33.6%-69.9%). The overall ORR of patients with advanced or recurrent endometrial cancer with molecular type pMMR was 16.1% (95% CI, 5.5%-30.3%). Conclusion: In our including studies, the patients with advanced or recurrent endometrial cancer with molecular types of dMMR and pMMR, following treatment with PD-1/PD-L1 inhibitors, the total ORR of patients with dMMR was higher than that of patients with pMMR. Since the current number of studies is not very large, it is possible that more studies will be published in the future and more precise results will be discussed further.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Han, Guo, Song, Ouyang and Wang.)

Han, S., et al. (2019). "Transcutaneous electrical nerve stimulation (TENS) for pain control in women with primary dysmenorrhoea." Cochrane Database of Systematic Reviews 2019(5): CD013331.
	This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy and safety of TENS on the basis of its frequency and acupoints, in comparison with placebo, no treatment, and other medical treatments for primary dysmenorrhoea.Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Han, X., et al. (2022). "Immune checkpoint inhibitors in advanced and recurrent/metastatic cervical cancer." Frontiers in Oncology 12: 996495.
	Cervical cancer (CC) poses a serious threat to women's health. Although many early-stage patients have a good prognosis, there are still a lack of effective therapies for advanced and recurrent/metastatic CC. In this context, immunotherapy and immune checkpoint inhibitors (ICIs) are particularly likely to play a role in the treatment of cervical tumors in a variety of disease settings. Some promising immune checkpoints include programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), which exert immunomodulatory effects as negative regulators of T-cell activation and suppress immune responses in cervical cancer through cancer cell immune evasion. Initial trials of ICIs for CC have shown encouraging results in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both monotherapy and combination strategies. Meanwhile, human papillomavirus, vaginal microecology and intestinal microenvironment play an important role in CC, which provides new treatment directions. This review analyzed a number of completed or ongoing clinical trials of ICIs in the treatment of advanced and recurrent/metastatic CC. And we also analyzed the important relationship between vaginal microecology and intestinal microecology with CC and their related immunotherapy prospects.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Han, Chang and Xia.)

Han, Y., et al. (2022). "Effect of vitamin D supplementation on reproductive biomarkers in polycystic ovary syndrome (PCOS) women: a systemic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Han, Y., et al. (2021). "Transcutaneous electrical acupoint stimulation for pregnancy outcomes in women undergoing in vitro fertilization: a protocol of systematic review and meta-analysis."
	
Hana, S., et al. (2021). "A Systematic Review of Behaviour Change Techniques in Digital Health for Midlife Women." PROSPERO International prospective register of systematic reviews.
	
Hanach, N., et al. (2021). "The effectiveness of telemedicine interventions, delivered exclusively during the postnatal period, on postpartum depression in mothers without history or existing mental disorders: A systematic review and meta-analysis." Midwifery 94: 102906.
	Background: Postpartum depression, one of the most common forms of depression, is highly prevalent worldwide among women during childbirth. Despite available treatments for postpartum depression, numerous barriers hinder women to access care including time, financial constraints, and childcare concerns. Telemedicine interventions are suggested to be feasible to prevent and improve postpartum depression.; Objective: To examine the effectiveness of telemedicine interventions - delivered exclusively during the postnatal period, on postpartum depression symptomatology in women with no history of mental disorders.; Design: A systematic review and meta-analysis of randomized controlled trials.; Methods: PubMed, Web of Science, Cochrane Library, and ProQuest Dissertations & Theses databases were used to identify relevant randomized controlled trials, until 7 January 2020. Studies were quality assessed using the Cochrane Library Risk of Bias Tool. The results of postpartum depression scores were pooled using a random-effects model. Intervention completion rate and participants' satisfaction were reported in a narrative form, as secondary outcomes.; Results: Ten trials including a total of 2366 participants, contributed data to the review. Seven studies were included in the quantitative synthesis. Women who received technology-based interventions, regardless of the type (web-based versus telephone-based), had a statistically significant improvement in postpartum depression (mean difference: -1.81, 95% CI: -2.68 to -0.93; P<.0001). The completion rate was 80% in the intervention groups compared to 76% in the control groups. Three studies reporting participants' satisfaction revealed that the participants were highly satisfied with the technology-based interventions.; Conclusion: Overall, telemedicine interventions appear to be promising in preventing and improving postpartum depression. Further larger-scale high-quality research is required to establish an evidence-based telemedicine approach, in terms of structure, content, and providers. Future economic evaluation is also vital to evaluate the long-term use of telemedicine in improving postpartum depression.; Competing Interests: Declaration of Competing Interest None declared. (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hande, V., et al. (2020). "Conventional vs. Volumetric Brachytherapy in the Treatment of Cervix Cancer: A Meta-Analysis of 30 Clinical Studies." Int. J. Radiat. Oncol. Biol. Phys. 108(3): e423-None.
	
Hande, V., et al. (2022). "Point-A vs. volume-based brachytherapy for the treatment of cervix cancer: A meta-analysis." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 170: 70-78.
	Background & Purpose: To report disease-free survival (DFS) for volume-based and point-A based brachytherapy (BT) in locally advanced cervical cancer.; Materials & Methods: We conducted a meta-analysis of studies assessing the effects of point-A and volume-based brachytherapy on 3-year DFS. Studies including stage I-IVA cervical cancer patients were included if standard treatment of concomitant chemo-radiotherapy and high-dose- or pulsed dose rate BT was delivered. The primary outcome was 3-year DFS, and secondary outcomes were 3-year local control (LC), 3-year overall survival (OS) and late toxicity. A random-effects subgroup meta-analysis was done.; Results: In total, 5499 studies were screened, of which 24 studies with 5488 patients were eligible. There was significant heterogeneity among point-A studies (1538 patients) (I 2 = 82%, p < 0.05) relative to volume-based studies (3950 patients) (I 2 = 58, p = 0.01). The 3-year DFS for point-A and volume-based studies were 67% (95% CI 60%-73%) and 79% (95% CI 76%-82%) respectively (p = 0.001). Three-year LC for point-A and volume-based studies were 86% (95% CI 81%-90%) and 92% (91%-94%) respectively (p = 0.01). The difference in 3-year OS (72% vs. 79%, p = 0.12) was not statistically significant. The proportion of prospectively enrolled patients was 23% for point-A studies and 33% for volume-based studies. There was no difference in late grade 3 or higher gastrointestinal (3% vs. 4%, p = 0.76) genitourinary toxicities (3% vs. 3% p = 0.45) between the two groups.; Conclusion: Volume-based BT results in superior 3-year DFS and 3-year LC. In the absence of randomized trials, this meta-analysis provides the best evidence regarding transition to 3D planning. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hanna, M. and Y. Moon Jee (2019). "A review of dexketoprofen trometamol in acute pain." Current medical research and opinion 35(2): 189-202.
	Objective: Dexketoprofen trometamol is a modified non-selective COX inhibitor with a rapid onset of action that is available as both oral and parenteral formulations. The aim of this narrative review was to assess the efficacy and tolerability/safety of dexketoprofen trometamol in acute pain states using the best available published scientific evidence (randomized controlled clinical trials and systematic reviews/meta-analyses).; Methods: Literature retrieval was performed via Medline, Embase and the Cochrane Library (from inception up to March 2017) using combinations of the terms "randomized controlled trials", "dexketoprofen", "celecoxib", "etoricoxib", "parecoxib" and "acute pain".; Results: Single-dose dexketoprofen trometamol provides effective analgesia in the treatment of acute pain, such as postoperative pain (dental and non-dental surgery), renal colic, acute musculoskeletal disorders and dysmenorrhea, and reduces opioid consumption in the postoperative setting. It has a rapid onset of action (within 30 minutes) and is well tolerated during short-term treatment. Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and tolerability of single-dose dexketoprofen trometamol appears to be consistent with that seen with celecoxib, etoricoxib and parecoxib in the acute pain setting.; Conclusion: In conclusion, dexketoprofen trometamol appears to provide similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has a rapid onset of action, is well tolerated, and has an opioid-sparing effect when used as part of a multimodal regimen in the acute pain setting.

Hanna, T. P., et al. (2020). "Mortality due to cancer treatment delay: systematic review and meta-analysis." BMJ (Clinical research ed.) 371: m4087.
	OBJECTIVE: To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Published studies in Medline from 1 January 2000 to 10 April 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. RESULT(S): The review included 34 studies for 17 indications (n=1272681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. CONCLUSION(S): Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Hansen, S., et al. (2021). "Impact of exercise on pain perception in women with endometriosis: A systematic review." Acta Obstetricia et Gynecologica Scandinavica 100(9): 1595-1601.
	Introduction: Endometriosis is challenging to treat. It is a painful and chronic inflammatory disorder that impacts up to 10% of women of reproductive age. Despite available surgical and medical treatment options, recurrence of symptoms is common. Available studies suggest that exercise may have a therapeutic effect on chronic inflammation and thereby on pain perception. This review evaluates whether exercise can decrease pain perception in women with symptomatic endometriosis.; Material and Methods: This systematic review was conducted according to PRISMA by searching databases Medline and Embase to locate randomized controlled trials and observational studies. Risk of bias was investigated using the Cochrane Collaboration Tool for the Evaluation of Randomized Controlled Trials and the ROBINS-I quality assessment scale. Inclusion criteria were women of reproductive age, laparoscopically confirmed diagnosis of endometriosis, and intervention of any type of exercise. All manuscripts were evaluated by two of the authors and when in doubt a third author was consulted. This review was registered in PROSPERO on November 14, 2020 (CRD42020212309).; Results: Six articles fulfilled the inclusion criteria and were included in this systematic review. Concerning exercise, two studies showed significant decrease in pain relief but the remaining studies showed either negative or no impact on pain relief. A meta-analysis could not be conducted because of the considerable heterogeneity among the included studies.; Conclusions: The present review does not indicate any beneficial effect of exercise on pain in women with endometriosis. There is a need for randomized controlled trials with correct power calculation, well-defined study groups and training programs to be able to answer the question of whether exercise can improve the pain experience in patients with endometriosis. (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Hanstede, M. M. F., et al. (2023). "Hormonal support in women with Asherman syndrome does not lead to better outcomes: A randomized trial." Reproductive Medicine and Biology 22(1): e12526.
	Purpose: The purpose of the study was to investigate if adjuvant hormones after successful adhesiolysis lead to a reduction in spontaneous recurrence of adhesions and influence reproductive outcomes. Method(s): A single-blind randomized controlled trial comparing administration of oral estrogen (the usual care group) with not giving estrogen (no estrogen) in women after successful adhesiolysis for Asherman syndrome. Women were included between September 2013 and February 2017, with a follow-up of 3 years to monitor recurrences and reproductive outcomes. Analyses were based on an intention to treat analyses. This study was registered under NL9655. Result(s): A total of 114 women were included. At 1 year, virtually all patients (except 3) were either having a recurrence or were pregnant. Women who did not receive estrogen did not have more recurrences of adhesions in the first year prior to pregnancy (66.1% in the usual care group, 52.7% in the no-estrogen group, p = 0.15). Of the women in usual care, 89.8% got pregnant within 3 years, and 67.8% got a living child; this was 83.6% and 60.0%, respectively, in the no-estrogen group (p = 0.33 and p = 0.39, respectively). Conclusion(s): Usual care does not lead to better outcomes as compared with not giving exogenous estrogen but is associated with side effects.Copyright © 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

Hao, D., et al. (2022). "Neuromodulation for Management of Chronic Pelvic Pain: A Comprehensive Review." Pain and therapy 11(4): 1137-1177.
	Introduction: Chronic pelvic pain (CPP) is a symptom that derives from a complex group of heterogeneous pathologies of the pelvic organs. The aim of this study was to review the available evidence on efficacy of neuromodulatory modalities including sacral neuromodulation, dorsal root ganglion stimulation, dorsal column neuromodulation, and pudendal nerve stimulation.; Methods: This narrative review focuses on updated information on neuromodulation for management of chronic pelvic pain. In 2022, we searched English-language studies on neuromodulation, pelvic pain, and chronic pain in a comprehensive search. We searched the following databases: PubMed, Medline, SciHub, Cochrane Database of Systematic Reviews, and Google Scholar. We used the following combinations of keywords: neuromodulation, pelvic pain, chronic pain, chronic pelvic pain, pelvic pain treatment. We tried to include as many recent manuscripts as possible (within the last 3 years) but also included papers older than 3 years if they were particularly relevant to our topic. We also attempted to search for, use, and cite primary manuscripts whenever possible.; Results: CPP is a challenging entity to treat because of diagnostic inconsistencies and limited evidence for therapeutic modalities. Our review found evidence suggestive of benefit for all modalities reviewed but the data was of overall low quality with numerous limitations. The literature highlights a lack of randomized controlled trials for neuromodulatory therapies but suggests a growing role for such techniques in treating refractory chronic pelvic pain syndrome (CPPS).; Conclusions: This review explores the available evidence on efficacy of neuromodulatory modalities for CPPS and contextualizes the results with information about the type of neuromodulation, lead location and waveform, pain outcomes and assessment timepoints, and reported adverse effects. (© 2022. The Author(s).)

Hao, H. J., et al. (2023). "Reproductive outcomes of ectopic pregnancy with conservative and surgical treatment: A systematic review and meta-analysis." Medicine (United States) 102(17): E33621.
	Background: Ectopic pregnancy (EP), one of the most common gynecological emergencies, is the major cause of maternal death in the first trimester and increases the incidence of infertility and repeat ectopic pregnancy (REP). The aim of this study was to compare the effects of different treatment methods for tubal EP on natural pregnancy outcomes. Method(s): We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials for observational studies on EP (published until October 30,2022 in English) comparing methotrexate (MTX) versus surgery, MTX versus salpingostomy, MTX versus salpingectomy, salpingostomy versus salpingectomy, and MTX versus expectant treatment. Our main endpoints included subsequent natural intrauterine pregnancy (IUP) and REP. We assessed the pooled data using Review Manager software (version 5.3) with a random effects model. Result(s): Of 1274 identified articles, 20 were eligible and 3530 participants were included in our analysis. There was a significant difference in the odds of subsequent IUP in tubal EP patients who underwent MTX compared with those who were treated with surgery [odds ratios (OR) = 1.52, 95% confidence interval (CI):1.20-1.92]. No significant difference was found in the odds of REP between the 2 groups (OR = 1.12, 95% confidence interval [CI]: 0.84-1.51). There was no significant difference in the odds of subsequent IUP and REP in patients after MTX compared to those after salpingostomy (OR = 1.04,95% CI: 0.79-1.38; OR = 1.10, 95% CI: 0.64-1.90). There was a significant difference in the odds of subsequent IUP in patients after MTX compared with those after salpingectomy (OR = 2.11, 95% CI: 1.52-2.93). No significant difference was found in the odds of REP between the 2 groups (OR = 0.98, 95% CI: 0.57-1.71). There was a significant difference in the odds of subsequent IUP between patients who underwent salpingostomy and those who underwent salpingectomy (OR = 1.61, 95% CI: 1.29-2.01). No significant difference was found in the odds of REP between the 2 groups (OR = 1.21, 95% CI: 0.62-2.37). There was no significant difference in the odds of subsequent IUP and REP in patients after MTX compared with those after expectant treatment (OR = 1.25, 95% CI: 0.64-2.45; OR = 0.69, 95% CI: 0.09-5.55). Conclusion(s): For hemodynamically stable tubal EP patients, MTX has advantages over surgery, particularly salpingectomy, in improving natural pregnancy outcomes. However, MTX is not inferior to salpingostomy and expectant treatment.Copyright © 2020 American Heart Association, Inc.

Hao, J., et al. (2024). "Pelvic floor muscle training in telerehabilitation: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics.
	PURPOSE: This systematic review aims to identify, critically appraise, and summarize current evidence regarding the feasibility and efficacy of pelvic floor muscle training in telerehabilitation. METHODS: Three bibliographic databases, PubMed, Embase, and Scopus were searched from inception to October 1, 2023. Clinical trials assessing the feasibility and efficacy of pelvic floor muscle training in telerehabilitation were eligible for inclusion. The Physiotherapy Evidence Database scale and National Institutes of Health Study Quality Assessment Tool were used for methodological quality assessment. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Meta-analyses were performed to determine the effects of pelvic floor muscle training in telerehabilitation. RESULTS: Five randomized controlled trials and three single cohort clinical trials were included in this review. Four studies were evaluated as good quality, and four as fair. Pelvic floor telerehabilitation was well tolerated and demonstrated good patient compliance and satisfaction. Pooled analysis indicated significant effects of pelvic floor telerehabilitation on the severity of urinary incontinence with a large effect size, pelvic floor muscle strength with a large effect size, and quality of life with a medium effect size. CONCLUSION: This systematic review demonstrates that pelvic floor muscle training in telerehabilitation is a feasible and effective approach and highlights its efficacy in patients with urinary incontinence. This review supports the application of pelvic floor muscle training in telerehabilitation and informs further clinical and research endeavors to incorporate digital health technologies in managing pelvic floor dysfunction.

Hao, J., et al. (2021). "Direct comparisons of efficacy and safety between actinomycin-D and methotrexate in women with low-risk gestational trophoblastic neoplasia: a meta-analysis of randomized and high-quality non-randomized studies." BMC Cancer 21(1): 1122.
	Background: Actinomycin-D (Act-D) and Methotrexate (MTX) are both effective first-line agents for low-risk gestational trophoblastic neoplasia (LRGTN) with no consensus regarding which is more effective or less toxic. The primary objective of this meta-analysis is to compare Act-D with MTX in the treatment of LRGTN. Method(s): We systematically searched electronic databases, conferences abstracts and trial registries for randomized controlled trials (RCTs) and high-quality non-randamized controlled trials (non-RCTs), comparing Act-D with MTX for patients with LRGTN. Studies were full-text screened for quality assessment and data extraction. Eligible studies must have reported complete remission rate. A fixed-effects meta-analysis was conducted to quantify the efficacy and safety of Act-D and MTX on odds ratios (ORs) and 95% confidence intervals (95%CIs), respectively. Result(s): A total of 8 RCTs and 9 non-RCTs (1674 patients) were included. In terms of efficacy, Act-D is superior to MTX in complete remission (80.2% [551/687] vs 65.1% [643/987]; OR 2.15, 95%CI 1.70 to 2.73). In the stratified analysis, patients from RCTs and non-RCTs both had a better complete remission from Act-D-based regimen (RCTs: 81.2% [259/319] vs 66.1% [199/301], OR 2.17, 95%CI 1.49 to 3.16; non-RCTs: 79.3% [292/368] vs 65.0% [444/686], OR 2.14, 95%CI 1.57 to 2.92). In terms of safety, patients receiving Act-D had higher risks of suffering nausea (OR 2.35, 95%CI 1.68 to 3.27), vomiting (OR 2.40, 95%CI 1.63 to 3.54), and alopecia (OR 2.76, 95%CI 1.60 to 4.75). Notably, liver toxicity (OR 0.38, 95%CI 0.19 to 0.76) was the only one that was conformed to have a higher risk for patients receiving MTX. In addition, the pooled results showed no significant difference of anaemia, leucocytopenia, neutropenia, thrombocytopnia, constipation, diarrhea, anorexia, and fatigue between Act-D and MTX. Conclusion(s): Our meta-analysis suggests that Act-D had better efficacy profile in general, and MTX had less toxicities in LRGTN. Future clinical trials should be better orchestrated to provide more valid data on efficacy and toxicity.Copyright © 2021, The Author(s).

Haouzi, D., et al. (2021). "Customized Frozen Embryo Transfer after Identification of the Receptivity Window with a Transcriptomic Approach Improves the Implantation and Live Birth Rates in Patients with Repeated Implantation Failure." Reproductive sciences (Thousand Oaks, Calif.) 28(1): 69-78.
	The aim of this prospective study was to evaluate outcome benefits expected in repeated implantation failure (RIF) patients (n = 217) after customized embryo transfer based upon identification of the receptivity window by transcriptomic approach using the Win-Test. In this test, the expression of 11 endometrial genes known to be predictive of endometrial receptivity is assessed by RT-PCR in biopsies collected during the implantation window (6-9 days after the spontaneous luteinizing hormone surge during natural cycles, 5-9 days after progesterone administration during hormone replacement therapy cycles). Then, patients underwent either customized embryo transfer (cET, n = 157 patients) according to the Win-Test results or embryo transfer according to the classical procedure (control group, n = 60). Pregnancy and live birth rates were compared in the two groups. The Win-Test showed that in 78.5% of women, the receptivity window lasted less than 48 h, although it could be shorter (< 24 h, 9.5%) or longer (> 48 h, 12%). This highlighted that only in 20% of patients with RIF the endometrium would have been receptive if the classical embryo transfer protocol was followed. In the other 80% of patients, the receptivity window was delayed by 1-3 days relative to the classical timing. This suggests that implantation failure could be linked to inadequate timing of embryo transfer. In agreement, both implantation (22.7% vs. 7.2%) and live birth rates per patient (31.8% vs. 8.3%) were significantly higher in the cET group than in the control group. cET on the basis of the Win-Test results could be proposed to improve pregnancy and live birth rates.ClinicalTrials.gov ID: NCT04192396; December 5, 2019, retrospectively registered.

Hardesty Melissa, M., et al. (2022). "OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab." Gynecologic Oncology 166(2): 219-229.
	Objective: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.; Methods: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety.; Results: Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff).; Conclusion: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.; Competing Interests: Declaration of Competing Interest MMH reports honoraria from Clinical Care Operations and GlaxoSmithKline; and advisory board fees from AstraZeneca-Merck, Immunogen and GlaxoSmithKline. TCK reports consulting and speakers' bureau fees from GlaxoSmithKline. GSW reports she served as PI for a clinical trial for which the institute received payment for conducting the trial from Abbvie, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cascadian Therapeutics, Celgene, Celldex Therapeutics, Daiichi Sankyo Pharma, Dana Farber Cancer Institute, G1Therapeutics, Genentech, H3BioMedicine Inc., Hoffmann-LaRoche, ImmunoGen, Incyte, Innocrin Pharm, Jansen, Lilly, Macrogenics, Medivation, Merrimack, NanoString Technologies, Novartis, Nucana, Odonate Therapeutics, Pfizer, Seattle Genetics, Sermonix Pharm, Taiho Oncology, and Tesaro. EH reports institutional research grant from Tesaro/GSK, Abbvie, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Arvinas, AtlasMedX, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Dana Farber Cancer Inst, Deciphera, eFFECTOR Therapeutics, Ellipses Pharma, EMD Serono, Fochon, FujiFilm, G1 Therapeutics, H3 Biomedicine, Harpoon, Hutchinson MediPharma, Immunogen, Immunomedics, Incyte, InvestisBio, Jacobio, Karyopharm, Leap Therapeutics, Lilly, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Merck, Mersana, Merus, Millenium, Molecular Templates, Myraid Genetic Labs, Novartis, Nucana, Olema, OncoMed, Onconova Therapeutics, ORIC Pharmaceuticals, Orinove, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Plexxikon, Radius Health, Regeneron, Repertoire Immune Medicine, Rgenix, Roche/Genentech, SeaGen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback, StemCentRx, Sutro, Syndax, Syros, Taiho, TapImmune, Treadwell Therapeutics, Verastem, Vincerx Pharma, Zenith Epigenetics, Zymeworks and institional consulting fees from Arcus, Arvinas, Black Diamond, Boehringer Ingelheim, CytomX, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roche/Genentech, SeaGen, Silverback Therapeutics. ELF has nothing to disclose. JB is an employee of GlaxoSmithKline. EKK is a fo mer employee of GlaxoSmithKline and reports stock and stock option ownership at the time of GSK employment. PW is an employee of GlaxoSmithKline. DG is an employee of GlaxoSmithKline. AC reports consulting fees from Tempus and advisory board fees from GlaxoSmithKline. HJG has nothing to disclose. GEK reports speaker bureau fees from AstraZeneca, Clovis, GlaxoSmithKline/Tesaro, and Myriad Genetics. RGM reports personal fees from Fujirebio Diagnostics Inc., and Humphries Pharmaceutical; and institutional grants from Angle Plc. DLR reports research contracts paid to her institution from Aravive, Arch Oncology, Celsion, Clovis, Deciphera, Fujifilm, GlaxoSmithKline, Harpoon, Karyopharm, Mersana, Plexxikon, Roche, Shattuck Labs, Syros, and Tesaro; honoraria fees from GOG Foundation; travel support from Tesaro; advisory board fees from AstraZeneca, Bayer, Deciphera, Foundation Medicine, Genentech, Mersana, and Tesaro/GlaxoSmithKline; and unpaid leadership as the vice chair of board of directors for National Ovarian Cancer Coalition. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Harendarczyk, L., et al. (2020). "[Impact of hysterectomy on urinary incontinence: A systematic review]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie.
	INTRODUCTION: The impact of a hysterectomy on urinary incontinence is a controversial subject in the literature. OBJECTIVE: To evaluate the prevalence and incidence of urinary incontinence after a hysterectomy as well as associated risk factors such as the type of hysterectomy, the surgical approach, urodynamic criteria and uterine disease. STUDY DESIGN: We conducted a systematic review in Pubmed database with the following keywords and MeSH term: hysterectomy, urinary incontinence. RESULTS: A total of 1340 articles were retrieved, 42 articles were selected for the final text analysis. The results of the different studies were heterogeneous. Hysterectomy seemed to increase the rate of sphincter deficiency (VLPP<60mmH2O for 20% of cases versus 1,7% without hysterectomy, P=0.003). The vaginal route could increase the incidence of UI with OR of 2.3 (95%CI 1.0-5.2). Subtotal hysterectomy appears to increase UI with a 0,74 RR for total hysterectomy (95%CI 0.58-0.94). A radical hysterectomy with nerve conservation would preserve urinary functions, unlike pelvic radiotherapy, which is responsible for irreversible nerve damage by demyelination and bladder fibrosis.

Harjee, R., et al. (2021). "Reproductive outcomes following surgical management for isthmoceles: A systematic review." Journal of Minimally Invasive Gynecology 28(7): 1291-1302.e1292.
	OBJECTIVE: To evaluate the efficacy of surgical management for isthmoceles in patients presenting with secondary infertility. DATA SOURCES: A systematic search was performed in MEDLINE, EMBASE and Cochrane Library databases from inception to May 2020. The search was limited to studies published in English. METHODS OF STUDY SELECTION: After the removal of duplicates, 3380 articles were screened for inclusion independently by two authors for studies. These two authors assessed for studies which focussed on reproductive aged women with a diagnosed isthmocele and secondary infertility who underwent any surgical intervention for defect repair with at least one of the goals being fertility restoration. TABULATION, INTEGRATION, AND RESULTS: 13 studies, comprised of 1 randomized controlled trial (RCT), 6 prospective case series and 6 retrospective case series describing 234 patients who underwent surgical management for an isthmocele and secondary infertility were included. The methodological quality of the included studies was assessed independently by both reviewers. Next, the data extraction was performed independently and then compared to ensure no discrepancies. 188 patients were treated by hysteroscopy, 36 by laparoscopy, 7 by laparotomy, and 3 through a vaginal approach. In total, 153 of the 234 patients (65.4%) achieved pregnancy across all studies within their respective study periods.. Pregnancy rates in the RCT were 21/28 (75%) for those treated via hysteroscopy compared to 9/28 (32%) for those untreated. Among studies reporting pregnancy outcomes, 101/116 (87.1%) pregnancies resulted in a live birth. The incidence of adverse events was 2%, including risk of reoperation. CONCLUSION: The results of this systematic review suggest that surgical treatment of isthmocele, particularly via hysteroscopy in patients with residual myometrial thickness (RMT) of at least 2.5mm, may be effective in treating isthmocele-associated secondary infertility with a relatively low complication rate. Further high-quality studies are needed due to the small sample sizes and observational nature of most available data.

Harris, E. (2023). "Nonhormone Treatment for Menopausal Hot Flashes Receives FDA Approval." JAMA 329(22): 1907.
	
Harris, M. L., et al. (2022). "Contraceptive use and contraceptive counselling interventions for women of reproductive age with cancer: a systematic review and meta-analysis." BMC Medicine 20(1): 489.
	Background: A lack of clarity exists regarding contraceptive uptake and counselling among women with cancer, despite these women having unique family planning needs. This study aimed to systematically review the available literature and produce an overall summary estimate of contraceptive use and counselling among women with cancer across the cancer care continuum. Method(s): A systematic search of articles reporting on contraceptive counselling and/or contraceptive use among women of reproductive age (15-49 years) with cancer across the cancer care continuum (e.g. diagnosis, treatment, survivorship) was conducted in MEDLINE, Embase, CINAHL, Maternity and Infant Care and Cochrane Library. Two independent reviewers conducted the data screening, data extraction and risk of bias assessment. Qualitative synthesis and meta-analyses were conducted to summarise the key findings. Result(s): We included 21 articles involving 3835 participants in this review. Studies varied according to the cancer population and time along the cancer care continuum it was assessed. Of the studies that reported the overall contraceptive prevalence among women diagnosed with cancer (n = 8), contraceptive use ranged from 25 to 92%. Of the four studies that focused on cancer survivors, the contraceptive prevalence ranged from 47 to 84%. When the prevalence of these studies was pooled, a crude summary prevalence of 64% (62% among women with cancer versus 68% among cancer survivors) was found. The rate of contraceptive counselling was assessed in ten studies. A pooled prevalence of 50% (44% among women with cancer versus 58% among cancer survivors) was found, with the prevalence ranging from 12 to 78% among individual studies depending on the point in the cancer care continuum that it was provided. When contraceptive counselling was provided, it was found to significantly increase contraceptive use although biases were identified in its application. Conclusion(s): Contraceptive counselling interventions as part of standard cancer care have the potential to not only empower women with cancer and cancer survivors to make informed choices regarding their reproductive health but also provide the ability to plan future pregnancies for times of better health.Copyright © 2022, The Author(s).

Harris, W. S., et al. (2021). "Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial." American journal of clinical nutrition 113(6): 1700‐1706.
	BACKGROUND: The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ‐linolenic acid (ALA), but the effects of exogenous estrogen on RBC n‐3 (ɷ‐3) PUFA concentrations are unknown. OBJECTIVE: We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n‐3 PUFA concentrations. METHODS: Postmenopausal women (ages 50‐79 y) were assigned to HT or placebo in the Women's Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65‐79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n = 560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n = 610). RBC n‐3 and n‐6 (ɷ‐6) PUFAs were quantified. RESULTS: Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n‐3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n‐6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged. CONCLUSIONS: HT increased RBC concentrations of the terminal n‐3 and n‐6 PUFAs (DHA and DPA n‐6). These findings are consistent with an estrogen‐induced increase in DHA and DPA n‐6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women's Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory.

Harrison, R. F., et al. (2021). "Cost-effectiveness of laparoscopic disease assessment in patients with newly diagnosed advanced ovarian cancer." Gynecologic Oncology 161(1): 56-62.
	Objective: To determine if laparoscopy is a cost-effective way to assess disease resectability in patients with newly diagnosed advanced ovarian cancer. Method(s): A cost-effectiveness analysis from a health care payer perspective was performed comparing two strategies: (1) a standard evaluation strategy, where a conventional approach to treatment planning was used to assign patients to either primary cytoreduction (PCS) or neoadjuvant chemotherapy with interval cytoreduction (NACT), and (2) a laparoscopy strategy, where patients considered candidates for PCS would undergo laparoscopy to triage between PCS or NACT based on the laparoscopy-predicted likelihood of complete gross resection. A microsimulation model was developed that included diagnostic work-up, surgical and adjuvant treatment, perioperative complications, and progression-free survival (PFS). Model parameters were derived from the literature and our published data. Effectiveness was defined in quality-adjusted PFS years. Results were tested with deterministic and probabilistic sensitivity analysis (PSA). The willingness-to-pay (WTP) threshold was set at $50,000 per year of quality-adjusted PFS. Result(s): The laparoscopy strategy led to additional costs (average additional cost $7034) but was also more effective (average 4.1 months of additional quality-adjusted PFS). The incremental cost-effectiveness ratio (ICER) of laparoscopy was $20,376 per additional year of quality-adjusted PFS. The laparoscopy strategy remained cost-effective even as the cost added by laparoscopy increased. The benefit of laparoscopy was influenced by mitigation of serious complications and their associated costs. The laparoscopy strategy was cost-effective across a range of WTP thresholds. Conclusion(s): Performing laparoscopy is a cost-effective way to improve primary treatment planning for patients with untreated advanced ovarian cancer.Copyright © 2021 Elsevier Inc.

Harrison, T. N. H. and R. J. Chang (2022). "Ovarian response to follicle-stimulating hormone in women with polycystic ovary syndrome is diminished compared to ovulatory controls." Clinical Endocrinology 97(3): 310-318.
	Objective: The mechanisms underlying ovarian dysfunction in polycystic ovary syndrome (PCOS) have not been definitively established. Our objective was to perform a detailed examination of ovarian responses to recombinant follicle-stimulating hormone (rFSH) in women with PCOS and controls. Design(s): This prospective, crossover, dose-response study included three rFSH stimulation periods. Each stimulation period involved three consecutive, daily, subcutaneous injections of rFSH administered at a single dose. Low, medium and high rFSH doses were weight-adjusted, corresponding to 0.5, 1.1 and 2.2 IU/kg/d, respectively. Stimulation periods occurred in randomized order and were separated by 8-week washouts. Patient(s): Thirty participants (8 PCOS and 22 controls) were studied. PCOS was defined by oligomenorrhea and clinical or biochemical androgen excess, excluding other aetiologies of ovulatory dysfunction. Measurements: Blood samples were obtained for hormone measurements before and 24 h after each rFSH injection. Result(s): Participants with PCOS had significantly greater body mass index, antral follicle count and circulating testosterone, anti-mullerian hormone (AMH) and luteinizing hormone concentrations compared with controls participants. Baseline estradiol (E2) concentrations were similar in both groups. At the lowest dose of rFSH, PCOS participants did not demonstrate E2 increments, whereas a significant increase occurred in controls. rFSH-induced E2 production per follicle was significantly reduced in PCOS participants compared with controls at all rFSH doses. Increasing T and decreasing AMH concentrations were associated with augmented E2 production per follicle. CoONCLUSIONS: Women with PCOS exhibited diminished initial E2 responses to rFSH compared with controls. These findings suggest that the mechanism of anovulation in PCOS may involve altered ovarian response to gonadotropins.Copyright © 2022 John Wiley & Sons Ltd.

Harter, P., et al. (2022). "Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer." Obstetrical and Gynecological Survey 77(4): 216-218.
	(Abstracted from N Engl J Med 2021;385:2123–2131) Standard of care treatment for advanced ovarian cancer involves primary macroscopic resection of all tumor followed by platinum-based combination chemotherapy with or without additional systemic therapy including bevacizumab or a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor. The Descriptive Evaluation of Preoperative Selection Criteria for Operability in Recurrent Ovarian Cancer (DESKTOP) series aims to assess the role of surgery in management of recurrent ovarian cancer.

Harter, P., et al. (2023). "Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): Results from the randomized, placebo (pbo)-controlled phase III DUO-O trial." Journal of Clinical Oncology 41(17 Supplement).
	Background: Olaparib (ola) maintenance (mtx) improved outcomes in pts with newly diagnosed AOC and a BRCAm (DiSilvestro J Clin Oncol 2023;41:609-17) or with bev in pts with homologous recombination deficiency (HRD+) tumors (Ray-Coquard Ann Oncol 2022: LBA29) in response to 1L treatment, but an unmet need remains. Combining an immune checkpoint inhibitor with an antiangiogenic agent and a PARP inhibitor may enhance antitumor effect (Banerjee Ann Oncol 2022: 529MO). The Phase III DUO-O trial (NCT03737643) evaluates PC + bev + durva, followed by mtx bev + durva + ola, in pts with non-tBRCAm AOC in the 1L setting. Method(s): Pts had newly diagnosed FIGO stage III or IV, high-grade epithelial, non-tBRCAm AOC and had completed upfront, or were planned to receive interval, debulking surgery and 1 cycle of PC 6 bev. At Cycle 2, pts were randomized 1:1:1 to Arm 1: PC + bev (15 mg/kg IV q3w) + durva pbo (up to 6 cycles) followed by mtx bev (15 mg/kg IV q3w; total 15 months [mo]) + durva pbo (total 24 mo) + ola pbo (total 24 mo); Arm 2: PC + bev + durva (1120 mg IV q3w) followed by mtx bev + durva (1120 mg IV q3w) + ola pbo; or Arm 3: PC + bev + durva followed by mtx bev + durva + ola (300 mg bid tablets). The primary endpoint, progression-free survival (PFS; modified RECIST 1.1 per investigator) in Arm 3 vs Arm 1, was tested first in the non-tBRCAm HRD+ population (GIS $42, Myriad MyChoice CDx) and then the intent-to-treat (ITT) population. Result(s): 1130 pts were randomized: 378 Arm 1, 374 Arm 2, and 378 Arm 3. At a prespecified interim analysis (DCO Dec 5, 2022), a statistically significant improvement in PFS was observed for Arm 3 vs Arm 1: HR 0.49 (95% CI 0.34-0.69; P,0.0001) and HR 0.63 (95% CI 0.52-0.76; P,0.0001) in the HRD+ and ITT populations, respectively; a consistent PFS effect was observed in the HRDsubgroup (HR 0.68, 95% CI 0.54-0.86). A numerical improvement in PFS was shown for Arm 2 vs Arm 1 (ITT population), but statistical significance was not reached (Table). During the study, any serious adverse events were reported in 34%, 43% and 39% of pts in Arms 1, 2 and 3, respectively. Conclusion(s): PC + bev + durva followed by mtx bev + durva + ola in pts with newly diagnosed non-tBRCAm AOC resulted in a statistically significant and clinically meaningful improvement in PFS vs PC + bev followed by mtx bev. Safety was generally consistent with the known profiles of each agent.

Hartner, G., et al. (2023). "The latest advances in the pharmacological management of endometriosis." Expert Opinion on Pharmacotherapy 24(1): 121-133.
	Introduction: Endometriosis is a benign disease, characterized by a wide range of symptoms and different degrees of severity, which is why therapy should be individually adapted to the patient's needs. Over the years, a lot of research has gone into finding new therapeutic approaches for this enigmatic disease.; Areas Covered: This review presents the latest advances in pharmacological management of endometriosis and is solely focused on studies published from 2010 to 2021.; Expert Opinion: Clinicians and researchers are constantly searching for new therapeutic strategies for endometriosis patients. As there are well-established treatments, however, any new medication should fulfill at least one of the three criteria: increased efficacy, comparable efficacy but a better safety profile, or treatments that have a lack of accompanying contraceptive effects that are seen in most endometriosis treatments. While some new substances show promising results, further studies are needed to demonstrate the fulfillment of one of the above-mentioned criteria.

Harvey, R. E., et al. (2022). "Impact of Estrogen Dosing on Cardiovascular Disease Risk Parameters in Women Experiencing Early Menopause due to Bilateral Oophorectomy." Menopause 29(12): 1450.
	Objective: Women who undergo early menopause (prior to age 46 years) secondary to bilateral oophorectomy experience an abrupt decrease in estrogen and other ovarian hormones, which is associated with an increased risk of cardiovascular disease (CVD). Administration of estrogen therapy (ET) given until the average age of natural menopause partially mitigates this risk. However, it is unclear whether standard dose ET, which is typically titrated to relieve vasomotor symptoms, is adequate to protect against development of CVD. It is not known whether ET titrated to a goal estradiol level characteristic of premenopausal women, performs better with respect to CVD risk reduction. The goal of this study was to compare the effect of standard dose ET versus ET titrated to premenopausal estradiol levels on blood pressure and subclinical CVD risk parameters in women experiencing early menopause due to bilateral oophorectomy. Design(s): We conducted a randomized, open-label trial to study 15 women who underwent bilateral oophorectomy prior to age 46 years. Eight women were treated with standard dose ET that was adjusted to manage their vasomotor symptoms (typically 2 mg oral estradiol or 100 mcg estradiol patch daily); and the other 7 were treated with titrated ET with a goal estradiol of 80-120 pg/ml (the average estradiol level in a premenopausal woman), irrespective of their symptoms. All participants were studied at baseline, and then at 6 and 12 months after the bilateral oophorectomy. At each time point, we assessed peripheral blood pressure and subclinical parameters of CVD (arterial stiffness and blood pressure reactivity to isometric handgrip and cold stress). Result(s): Women who were treated with standard dose ET and women treated with titrated ET did not differ in age (39+/-5 vs. 39+/-5 years, respectively; p=0.89). Serum estradiol levels did not change across time (baseline, 6-months, and 12-months); however, serum estradiol levels were lower in women receiving standard dose ET (69.3+/-46.7, 52.9+/-32.5, and 81.6+/-16.4 pg/mL, across time respectively) compared to women receiving titrated ET (98.0+/-45.0, 179.4+/-81.1, and 146.9+/-105.1 pg/mL, across time respectively; group effect p=0.005, time effect p=0.20, interaction p=0.058). Systolic blood pressure did not differ across time or between the two groups: standard group: 120+/-10, 115+/-8, and 114+/-14 mmHg; titrated group: 127+/-15, 122+/-19, and 133+/-18 mmHg (group effect p=0.09, time effect p=0.35, interaction p=0.17). Diastolic blood pressure also did not differ: standard group: 77+/-5, 71+/-5, and 71+/-8 mmHg; titrated group: 80+/-8, 76+/-12, and 84+/-16 mmHg (group effect p=0.12, time effect p=0.07, interaction p=0.07). Arterial stiffness (group effect p=0.54, time effect p=0.29, interaction p=0.94), blood pressure reactivity to isometric handgrip (group effect p=0.47, time effect p=0.86, interaction p=0.20), and blood pressure reactivity to cold stress (group effect p=0.68, time effect p=0.57, interaction p=0.50) did not differ across time or between groups. Conclusion(s): In women experiencing early menopause due to bilateral oophorectomy prior to the age of 46 years, standard dose ET, adjusted to manage vasomotor symptoms, resulted in lower estradiol levels than titrated ET, which resulted in estradiol levels characteristic of the premenopausal stage. Despite the differences in estradiol levels, blood pressure, arterial stiffness, and blood pressure reactivity to isometric handgrip and cold stress were not different in the two ET groups. This could either signify a lack of effect of estradiol dose and level on these parameters, or this could be a result of the short duration of study. Differences in the CVD risk parameters may become apparent in the standard dose ET versus titrated ET group with a longer duration of comparison.

Hasegawa, H., et al. (2021). "Gonadotroph Pituitary Adenoma Causing Treatable Infertility and Ovarian Hyperstimulation Syndrome in Female Patients: Neurosurgical, Endocrinologic, Gynecologic, and Reproductive Outcomes." World neurosurgery 150: e162-e175.
	Background: Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described.; Methods: We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects.; Results: The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14.; Conclusions: Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hashim, H. A., et al. (2023). "Retraction Note: laparoscopic ovarian diathermy after clomiphene failure in polycystic ovary syndrome: is it worthwhile? A randomized controlled trial [Retraction notice for CN-00835360]." Archives of Gynecology and Obstetrics 307(5): 1661.
	The Editor‐in‐Chief has retracted this article. The study reported in this article was included as part of the PhD thesis of Hatem Abu Hashim entitled “Ovulation induction in polycystic ovary syndrome (PCOS): An appraisal of different strategies” submitted to Vrije Universiteit Brussel (VUB) in 2013. In 2020 [1] serious concerns were raised about the data reported and Hatem Abu Hashim responded [2]. An investigation by VUB was followed by a request for Second Advice from the Flemish Commission for Research Integrity (VCWI). The investigations by VUB and the VCWI concluded that there had been serious violations of scientific integrity including fabrication, and recommended retraction. Hatem Abu Hashim does not agree with this retraction and has provided a copy of their submission to the VUB and VCWI investigations to the Editor‐in‐Chief. None of the other authors has responded to correspondence from the Publisher about this retraction.

Hassan, F., et al. (2023). "Neurokinin 1/3 receptor antagonists for menopausal women: A current systematic review and insights into the investigational non-hormonal therapy." Medicine 102(23): e33978.
	Background: Over 75% of menopausal women experience vasomotor symptoms (VMS), such as night sweats and hot flashes. Despite the prevalence of these symptoms, there is limited data on non-hormonal therapies to alleviate them.; Methods: PubMed, Cochrane, Scopus, Ovid, Web of Science, and ClinicalTrials.Gov were searched for relevant studies. The search was performed using the following keywords, which were customized to suit the specific databases/registers: menopause, women, neurokinin 3, and/or Fezolinetant. The search was conducted until December 20, 2022. This systematic review was conducted in compliance with the PRISMA Statement 2020 guidelines.; Results: A total of 326 records were found, with 10 studies (enrolling 1993 women) selected for inclusion. The women received 40-mg doses of NK1/3 receptor antagonists twice daily, with follow-ups at 1 to 3 weeks. Moderately strong evidence was found suggesting that NK1/3 receptor antagonists can help limit the frequency and severity of hot flashes in menopausal women.; Conclusion: While the results should be interpreted with caution until further clinical trials validate the efficacy and safety of NK1/3 receptor antagonists among menopausal women, these findings suggest that they are promising targets for future pharmacological and clinical studies in addressing vasomotor symptoms.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hassan, H., et al. (2024). "Long-term outcomes of hysterectomy with bilateral salpingo-oophorectomy: a systematic review and meta-analysis." American Journal of Obstetrics and Gynecology 230(1): 44-57.
	Objective: This study aimed to provide an up-to-date systematic review of "the long-term outcomes of bilateral salpingo-oophorectomy at the time of hysterectomy" and perform a meta-analysis for the reported associations.; Data Sources: Our study updated a previous systematic review by searching the literature using PubMed, Web of Science, and Embase for publications between January 2015 and August 2022.; Study Eligibility Criteria: Our study included studies of women who had a hysterectomy with bilateral salpingo-oophorectomy vs women who had a hysterectomy with ovarian conservation or no surgery.; Methods: The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations. Adjusted hazard ratios were extracted and combined to obtain fixed effect estimates.; Results: Compared with hysterectomy or no surgery, hysterectomy with bilateral salpingo-oophorectomy in young women was associated with decreased risk of breast cancer (hazard ratio, 0.78; 95% confidence interval, 0.73-0.84) but with an increased risk of colorectal cancer (hazard ratio, 1.27; 95% confidence interval, 1.10-1.47). In addition, it was associated with an increased risk of total cardiovascular diseases, coronary heart disease, and stroke with hazard ratios of 1.18 (95% confidence interval, 1.11-1.25), 1.17 (95% confidence interval, 1.10-1.25), and 1.20 (95% confidence interval, 1.10-1.31), respectively. Compared with no surgery, hysterectomy with bilateral salpingo-oophorectomy before the age of 50 years was associated with an increased risk of hyperlipidemia (hazard ratio, 1.44; 95% confidence interval, 1.25-1.65), diabetes mellitus (hazard ratio, 1.16; 95% confidence interval, 1.09-1.24), hypertension (hazard ratio, 1.13; 95% confidence interval, 1.06-1.20), dementia (hazard ratio, 1.70; 95% confidence interval, 1.07-2.69), and depression (hazard ratio, 1.39; 95% confidence interval, 1.22-1.60). The evidence on the association with all-cause mortality in young women showed substantial heterogeneity between the studies (I 2 =85%; P<.01).; Conclusion: Hysterectomy with bilateral salpingo-oophorectomy was associated with multiple long-term outcomes. The benefits of the addition of bilateral salpingo-oophorectomy to hysterectomy should be balanced against the risks. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Hassanzadeh, R., et al. (2023). "The effect of fenugreek on the severity of dysmenorrhea: a systematic review and meta-analysis." Current drug research reviews.
	Introduction: Dysmenorrhea is the most common periodic pain, which affects more than 50% of women with regular menstruation. Fenugreek is one of the medicinal plants with analgesic properties. This study aimed to determine the effect of fenugreek application in the severity of dysmenorrhea and its side effects in women with dysmenorrhea. PICO: population: women with dysmenorrhea; intervention: fenugreek; comparison: control groups; and outcome: reduction in the severity of dysmenorrhea and its side effects Methodology: English database (PubMed, Cochrane Library, Scopus, and Web of Science) and Persian database [SID (Scientific Information Database) and Magiran] were used for research until February 11, 2023, using the keywords "Dysmenorrhea [Mesh]," "Foenum [Mesh]," "fenugreek [Mesh]," and "Trigonella [Mesh]." The reference list of the selected articles was also checked. The quality assessment was conducted through the Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0. The RevMan 5.3 software was used to analyze and report the data of the entered studies. Meta-analysis results were reported with the standardized mean difference (95% confidence interval). A subgroup analysis was performed based on the type of control groups. The quality of evidence was assessed using the GRADE approach.; Results: After removing duplicates and ineligible cases, four articles were included in the systematic review out of the 1526 records obtained. The results showed that the pain intensity caused by primary dysmenorrhea decreased with fenugreek compared to placebo (pooled result SMD: -2.21; 95% CI: -3.26 to -1.17; Z: 4.17; P <0.001). There was no significant difference between fenugreek with mefenamic acid (SMD: 0.05; 95% CI: -0.57 to 0.67; Z: 0.17; P = 0.86) and fenugreek with Chandrasura churna (SMD: 0.06; 95% CI: -0.56 to 0.68; Z: 0.19; P = 0.85). Bias, in terms of incomplete outcome data and selective reporting, was low risk in all studies, and the available evidence was low quality according to the GRADE approach.; Conclusion: The results showed that the effect of fenugreek on pain intensity in dysmenorrhea is highly uncertain. The true effect is likely to be substantially different from the estimate of effect. Regarding the importance of the health and quality of life of women of reproductive age and the low quality of evidence of the studies, clinical trials with stronger methodology are suggested in this field. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hatfield, E., et al. (2020). "Use of low-dose naltrexone in the management of chronic pain conditions: A systematic review." Journal of the American Dental Association (1939) 151(12): 891.
	Background: The authors aimed to evaluate the efficacy of low-dose naltrexone in the management of chronic pain conditions and determine its potential use in orofacial pain management.; Methods: A comprehensive literature review was completed in the PubMed/MEDLINE, Embase, Cumulated Index to Nursing and Allied Health Literature, Dentistry and Oral Sciences Source Library databases up through June 17, 2019, using terms such as neurogenic, inflammation, naltrexone, temporomandibular, and chronic pain. The primary outcome was reduction in pain intensity and, secondarily, improvement in quality of life.; Results: A total of 793 studies were obtained with the initial search and 8 articles were selected for evaluation. Of these 8 articles, 4 were case reports, 3 were clinical studies, and 1 was a randomized controlled trial. Six studies included data on fibromyalgia, 2 studies included data on chronic regional pain syndrome, and 1 examined multiple diagnoses, including fibromyalgia, interstitial cystitis, and chronic pelvic pain. The primary outcome of all of the studies was pain intensity reduction.; Conclusions and Practical Implications: Low-dose naltrexone provides an alternative in medical management of chronic pain disorders as a novel anti-inflammatory and immunomodulator. It can offer additional management options, as orofacial pain conditions share characteristics with other chronic pain disorders. Owing to the size and heterogeneity of the studies, more large-scale studies are needed, along with additional studies assessing orofacial pain response to low-dose naltrexone. (Copyright © 2020 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Hatırnaz, Ş., et al. (2022). "Oocyte maturation abnormalities - A systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina." Turkish Journal of Obstetrics and Gynecology 19(1): 60-80.
	A small proportion of infertile women experience repeated oocyte maturation abnormalities (OMAS). OMAS include degenerated and dysmorphic oocytes, empty follicle syndrome, oocyte maturation arrest (OMA), resistant ovary syndrome and maturation defects due to primary ovarian insufficiency. Genetic factors play an important role in OMAS but still need specifications. This review documents the spectrum of OMAS and to evaluate the multiple subtypes classified as OMAS. In this review, readers will be able to understand the oocyte maturation mechanism, gene expression and their regulation that lead to different subtypes of OMAs, and it will discuss the animal and human studies related to OMAS and lastly the treatment options for OMAs. Literature searches using PubMed, MEDLINE, Embase, National Institute for Health and Care Excellence were performed to identify articles written in English focusing on Oocyte Maturation Abnormalities by looking for the following relevant keywords. A search was made with the specified keywords and included books and documents, clinical trials, animal studies, human studies, meta-analysis, randomized controlled trials, reviews, systematic reviews and options written in english. The search detected 3,953 sources published from 1961 to 2021. After title and abstract screening for study type, duplicates and relevancy, 2,914 studies were excluded. The remaining 1,039 records were assessed for eligibility by full-text reading and 886 records were then excluded. Two hundred and twenty seven full-text articles and 0 book chapters from the database were selected for inclusion. Overall, 227 articles, one unpublished and one abstract paper were included in this final review. In this review study, OMAS were classified and extensively evaluatedand possible treatment options under the light of current information, present literature and ongoing studies. Either genetic studies or in vitro maturation studies that will be handled in the future will lead more informations to be reached and may make it possible to obtain pregnancies.

Haussmann, J., et al. (2024). "Premenstrual syndrome and premenstrual dysphoric disorder-Overview on pathophysiology, diagnostics and treatment." Nervenarzt.
	Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as a differential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From a pathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by a complex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.Copyright © The Author(s) 2024.

Hawkins Summer, S. (2023). "Screening and the New Treatment for Postpartum Depression." Journal of obstetric, gynecologic, and neonatal nursing : JOGNN 52(6): 429-441.
	In August 2023, the U.S. Food and Drug Administration approved Zurzuvae (zuranolone) as the first oral medication to treat postpartum depression. Despite recommendations to screen and treat depression during pregnancy and after birth, perinatal depression is still considered under-detected and under-treated. In this column, I review screening recommendations and the new pharmacological treatment for postpartum depression, research findings on gaps in the cascade of mental health care, integrative care models, and recommendations from professional organizations on screening and treating postpartum depression within broader systems of mental health care. (Copyright © 2023. Published by Elsevier Inc.)

hazem, s., et al. (2023). "The efficacy of intrauterine infusion of platelet rich plasma in women undergoing assisted reproduction: A systematic review and meta-analysis."
	
Hazimeh, D., et al. (2023). "53 Planned interim analysis of a randomized trial comparing epidural to surgical site infiltration with liposomal bupivacaine for gynecologic oncology patients undergoing laparotomy." Gynecologic Oncology Reports 48(Supplement 1): S27.
	Objectives: Efficacy interim analysis of a randomized trial comparing epidural analgesia (EA) to surgical site infiltration with liposomal bupivacaine (LB) in patients undergoing laparotomy on a gynecologic oncology enhanced recovery after surgery (ERAS) program. This is an investigator-initiated study funded by a research grant from Pacira Biosciences; NCT04117074). Method(s): Patients (n=40) with suspected or known gynecologic cancer and planned for laparotomy were randomized 1:1 to EA or surgical site inifiltration with LB. Participants rated their postoperative pain intensity on a scale of 0 to 10 every 6 hours and immediately before opioid medication. Coprimary enpoints were mean area under the curve (AUC) of visual analog scale (VAS) pain intensity scores and total opioid consumption from 0 to 48 hours postoperatively. The mean AUC of VAS pain intensity scores incorporates opioid consumption. Quality of recovery was assayed daily using the quality of recovery-15 (QoR-15) survey instrument. Two sample t-tests and Wilcoxon rank-sum tests were used to compare the arms. Result(s): Two of 20 patients randomized to EA were found ineligible for enrollment and one withdrew. All patients randomized to surgical site infiltration with LB enrolled. Mean age and BMI were 56+/-14 years and 30.6+/-13.6 kg/m2. The majority had invasive cancer (81%). Participants reported race as White (72.2%), Black (19.4%) and Asian (5.6%). Mean estimated blood loss was 659+/-987 mL and mean duration of surgery was 6.7+/-2.0 hours. Median length of stay was 4 days and did not differ between the two arms. Mean pain intensity scores were similar for EA and LB (mean 3.7 vs 3.9), but total opioid consumption was lower in the LB arm compared to EA (mean IV MME 34.1 vs 48.2). QOR-15 scores on postoperative day 1 and on day of discharge did not differ between the arms (Table 1). One case of dural puncture occured in the EA arm. The incidence of hypotension was similar between the arms; grade 1-2 and grade 3-4 hypotension were observed with EA in 31.3% and 12.5% of cases and in 25% and 10% of patients who received LB. [Formula presented] Conclusion(s): Interim efficacy data suggest that surgical site infiltration with LB may be a valuable alternative to EA for gynecologic oncology patients undergoing laparotomy on ERAS protocols. The trial has exceeded 50% of the accrual goal (n=106) for final analysis.Copyright © 2023 Elsevier Inc.

He, J. and X. Ke (2023). "Efficacy and toxicity of Mirvetuximab Soravtansine in second-line and above treatment of advanced ovarian cancer: a meta-analysis."
	
He, M., et al. (2023). "Effect of resistance training on lipid profile in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials." European Journal of Obstetrics, Gynecology, and Reproductive Biology 288: 18-28.
	Objective: Physical exercise decreases cardiovascular risk and can alter the lipid profile in postmenopausal women. Although it is believed that resistance training can potentially decrease serum lipid levels in postmenopausal females, the evidence remains inconclusive. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to clarify the impact of resistance training on the lipid profile in postmenopausal women.; Methods: Web of Science, Scopus, PubMed/Medline and Embase were searched. RCTs that evaluated the effect of resistance training on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were included in this review. Effect size was estimated using the random effects model. Subgroup analyses based on age, duration of intervention, pre-enrolment serum lipid levels and body mass index were performed.; Results: Data pooled from 19 RCTs revealed that resistance training can reduce TC [weighted mean difference (WMD) -11.47 mg/dl; p = 0.002], LDL-C (WMD -8.48 mg/dl; p = 0.01) and TG (WMD -6.61 mg/dl; p = 0.043) levels. TC levels decreased particularly in subjects aged < 60 years (WMD -10.77 mg/dl; p = 0.003), in RCTs lasting < 16 weeks (WMD -15.70 mg/dl; p = 0.048), and in subjects with hypercholesterolaemia (WMD -12.36 mg/dl; p = 0.001) or obesity (WMD -19.35 mg/dl; p = 0.006) before RCT enrolment. There was a significant decrease in LDL-C (WMD -14.38 mg/dl; p = 0.002) levels in patients with LDL-C ≥ 130 mg/dl before trial enrolment. Resistance training reduced HDL-C (WMD -2.97 mg/dl; p = 0.01) levels particularly in subjects with obesity. TG (WMD -10.71 mg/dl; p = 0.01) levels decreased particularly when the intervention lasted < 16 weeks.; Conclusion: Resistance training can decrease TC, LDL-C and TG levels in postmenopausal females. The impact of resistance training on HDL-C levels was small, and was only observed in individuals with obesity. The effect of resistance training on the lipid profile was more notable in short-term interventions and in postmenopausal women with dyslipidaemia or obesity before trial enrolment.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

He, Q., et al. (2020). "The efficacy and safety of acupuncture for perimenopause symptom compared with different sham acupuncture control groups: A protocol of systematic review and meta-analysis." Medicine 99(10): e19366.
	Background: Perimenopause is a period that every woman must go through, most people are more or less affected by perimenopausal symptoms, it to affect women's health, work, life, and economy. As acupuncture treatment is more and more increasing in perimenopausal symptoms, there have also been many clinical trials about it. But the results of the trials are inconsistent. Therefore, we will conduct a systematic review and meta-analysis of the safety and efficacy of perimenopausal symptoms treated with acupuncture.; Methods: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. RCT study on different acupuncture interventions for perimenopausal symptoms will be searched in 8 databases (PubMed, EMBASE, the Cochrane Library, the web of science, CBM, CNKI, WAN FANG, and VIP). Besides, the search will also be performed on the clinical trial research platform if necessary. The primary outcome that will be extracted: the Flushes per 24 hours, the Frequency of hot flashes, the severity of hot flashes, the menopause-related symptom score, the treatment efficacy, the adverse event. Endnote software X8 will be used for study selection, STATA 13.0 and Review Manager software 5.3 will be used for analysis and synthesis. These studies selection, data extraction, and risk of bias assessment will be conducted by 2 independent reviewers.; Results: This study will provide the results: 1. the primary and secondary outcome indicators of different acupuncture intervention measures (traditional hand acupuncture, moxibustion, ear acupuncture, laser, acupressure points) for perimenopausal symptoms. 2. The effects of different control groups (medicine control, routine care, waiting, and sham acupuncture control) on the analysis results will be reported, especially the effects of different sham acupuncture control (invasive/noninvasive) on the analysis results.; Conclusion: This systematic review and meta-analysis study hopes to provide useful evidence for better use of different types of acupuncture in treat perimenopausal symptoms and better design of control groups in related clinical trials. In addition, the research conclusion will be published in peer journals.OSF REGISTRATION NUMBER DOI 10.17605/OSF.IO/VZCKU Ethics and dissemination This conclusion of the study will be published in peer journals. The ethical approval is not required because there is no direct involvement of human.

He, Q.-D., et al. (2021). "Efficacy and Safety of Acupuncture Vs. Hormone Therapy for Menopausal Syndrome: A Systematic Review and Meta-Analysis." The American journal of Chinese medicine 49(8): 1793-1812.
	Menopausal syndrome (MPS) is a common gynecological disorder around the time of menopause, and hormone therapy (HT) is the first-line treatment for it. However, HT is prone to cause adverse reactions in MPS patients treated with HT. Acupuncture is a popular non-pharmaceutical therapy for MPS, but the differences in the efficacy and safety between acupuncture and HT remain unclear. The purpose of this evidence-based study is to address this issue. Five databases were searched for potentially eligible RCTs. All RCTs comparing acupuncture with HT in the treatment of MPS were included in this study. The clinical effective rate was the primary outcome. Kupperman index, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E[Formula: see text], and side effects were the secondary outcomes. A total of 15 RCTs recruiting 1376 MPS patients were included. Results of meta-analysis showed that compared with HT, acupuncture significantly improved clinical effective rate (RR = 1.09, 95% CI 1.03 to 1.16, [Formula: see text] = 0.005), decreased the Kupperman index (WMD = -2.55, 95% CI = -2.93 to -2.17, [Formula: see text] < 0.00001) and the incidence of side effects (RR = 0.14, 95% CI = 0.06-0.32, [Formula: see text] < 0.00001). There were no statistically significant differences in serum FSH (WMD = -1.36, 95% CI = -3.25-0.53, [Formula: see text] = 0.16), E 2 (WMD = -1.11, 95% CI = -2.59-0.37, [Formula: see text] = 0.14), or LH (WMD = -1.87, 95% CI = -4.58-0.83, [Formula: see text] = 0.17) between the acupuncture and HT groups. Based on the current evidence, manual acupuncture is safer and more effective than HT and is recommended for the treatment of MPS, but the evidence for the efficacy of other types of acupuncture is inconclusive.

He, X. and Z. Li (2022). "Ostomy Does Not Lead to Worse Outcomes After Bowel Resection With Ovarian Cancer: A Systematic Review." Frontiers in Oncology 12: 892376.
	Background: Debulking cytoreduction surgery with bowel resection is a common intervention for ovarian cancer. It is controversial whether ostomy causes worse survival outcomes and how clinical physicians should choose which patients to undergo ostomy. During this study, we performed a systematic review to determine whether ostomy leads to worse outcomes after bowel resection compared to anastomosis. We also summarized the possible indications for ostomy.; Methods: We searched PubMed, Embase, and Cochrane for articles containing the phrase "ovarian cancer with bowel resection" that were published between 2016 and 2021. We included studies that compared primary anastomosis with ostomy. We mainly focused on differences in the anastomotic leakage rate, length of hospital stay, overall survival, and other survival outcomes associated with the two procedures.; Results and Conclusion: Of the 763 studies, three were ultimately included in the systematic review (N=1411). We found that ostomy did not contribute to worse survival outcomes, and that the stoma-related complications were acceptable. Indications for ostomy require further study. Bowel resection segment margins and the distance from the anastomosis to the anal verge require consideration.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 He and Li.)

He, X., et al. (2021). "Protective Effect of Mannitol on Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-Analysis." Frontiers in Oncology 11: 804685.
	Introduction: Cisplatin, a chemotherapeutic drug, is widely used for the treatment of various malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity, which is controversial. This study aimed to evaluate the efficacy and safety of a hydration regimen containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis. Method(s): Potential records from PubMed, EMBASE, Cochrane Library, and ClinicalTrials that met the inclusion criteria were included from inception to May 2021. Cochrane Collaboration tools were used to assess the risk of bias in the included studies. Jadad's and NOS scores were applied to assess the quality of randomized controlled trials (RCTs) and case-control studies. A random-effects model or fixed-effects model was used depending on the heterogeneity. Subgroup analyses were performed to evaluate the potential study characteristics. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated. Result(s): Four RCTs and seven case-control studies involving 4168 patients were included. Pooled results showed that mannitol use could reduce the incidence of cisplatin-induced nephrotoxicity (OR = 0.66, 95% CI [0.45-0.97], p = 0.03), especially reducing grade 3 nephrotoxicity events according to CTCAE 4.0 (OR = 0.37,95% CI [0.16-0.84]). Moreover, mannitol use was not significantly associated with creatinine clearance, serum creatine, and electrolyte disturbance (p > 0.05). Gastrointestinal cancer (OR = 0.36, 95% CI [0.15-0.83], p = 0.02) and urinary tract cancer (OR = 0.32,95% CI [0.14-0.73], p = 0.007) may be more sensitive to mannitol, although the test for overall effect was significantly different (OR = 0.66, 95% CI [0.49-0.89], p = 0.007). For patients with diabetes and hypertension, mannitol may worsen renal function (OR = 1.80, 95% CI [1.18-2.72], p = 0.006; OR = 2.19, 95% CI [1.50, 3.19], p < 0.0001, respectively). Mannitol may have a better protective effect when doses of mannitol were >= 25 g (OR = 0.58, 95% CI [0.39-0.88], p = 0.01) and doses of cisplatin < 75 mg/m2 (OR = 0.59, 95% CI [0.36-0.94], p = 0.03). It revealed that mannitol use was likely to cause nausea or vomiting (OR = 1.86, 95% CI [1.20-2.89], p = 0.006). Conclusion(s): Current evidence revealed that mannitol was an effective and safe drug to reduce cisplatin-induced nephrotoxicity events, especially Grade 3 events. However, it may cause more nausea/vomiting events and deteriorate renal function in patients with diabetes or hypertension. We also found that mannitol had the best effect when mannitol was >= 25 g in total or cisplatin was < 75 mg/m2. Meanwhile, mannitol may have a better effect on gastrointestinal and urinary tract cancers. Systematic Review Registration: crd. york. ac. uk/PROSPERO, CRD 42021253990Copyright © 2021 Li, He, Ruan, Ye, Wen, Song, Hu, Chen, Peng and Li.

He, Y., et al. (2024). "Comparison of the Efficacy and Safety of Ultrasound-Guided Sclerotherapy versus Cystectomy for the Treatment of Ovarian Endometriomas: A Systematic Review and Meta-Analysis." Current Women's Health Reviews 20(2): e280323215050.
	Background: Ultrasound-guided sclerosis has been used to treat ovarian endometriotic cysts since 1988. However, compared with cystectomy, sclerotherapy's effectiveness and safety are questionable. Objective(s): To compare ultrasound-guided sclerotherapy and ovarian cystectomy in the treatment of ovarian endometriosis through a systematic review and meta-analysis. Method(s): PubMed-MEDLINE, EMBASE, Cochrane, and Scopus databases were searched, and related literature was collected. The two treatments' recurrence rate, pain relief rate, pregnancy rate, tech-nical success rate, and complication rate were directly compared. Result(s): Six studies (386 patients) were included. The risk of recurrence with sclerotherapy was higher than that with cystectomy (OR 1.57, p = 0.52). Subgroup analysis showed that an indwelling time > 10 min was not significantly different regarding recurrence risk between sclerotherapy and cystectomy (OR 1.01, p = 0.99). When the indwelling time was <= 10 min, the risk of recurrence with sclerotherapy was significantly higher than that with cystectomy (OR 22.01, p = 0.001). The pregnancy rate after cystectomy was lower than that after sclerosis (OR 1.67, p = 0.22). Complications in the study were graded according to the Clavien-Dindo classification and statistical analysis showed that the probabil-ity of serious complications (Grade III-V) with cystectomy was higher than that with sclerosis (16.67% vs. 0%). Conclusion(s): Ultrasound-guided sclerotherapy was not inferior to cystectomy in terms of recurrence rate or pregnancy rate, and the incidence of severe complications was lower than that in the cystectomy group. Sclerotherapy is a safe and effective alternative treatment for ovarian endometriosis.Copyright © 2024 Bentham Science Publishers.

He, Z. and A. Miao (2024). "Lymph node dissection before initial treatment for locally advanced cervical cancer: a systematic review and meta-analysis."
	
Health, B., et al. (2022). Herbal Nutraceutical Supplementation on Vasomotor Symptoms in Menopausal Women.
	No Results Available Dietary Supplement: JDS-HF 3.0|Dietary Supplement: Placebo To determine the effects of the Test Product (TP) compared to placebo on hot flash symptoms as determined by the Hot Flash Related Daily Interference Scale (HFRDIS).|To determine the effect of the TP compared to the placebo on overall menopausal symptoms as determined by the Greene Climacteric Scale (GCS).|To determine the effect of the TP compared to the placebo on overall menopausal symptoms as determined by the Menopausal Rating Scale (MRS).|To determine the effect of the TP compared to the placebo on sleep quality as determined by the Pittsburgh Sleep Quality Index (PSQI).|To determine the effect of the TP compared to the placebo on quality of life as determined by the Menopause-Specific Quality of Life (MENQOL) questionnaire. Female Not Applicable 64 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Supportive Care B01-22-01-T0032 October 1, 2023

Health, F. (2021). Preoperative Analgesia by Infiltration of the Pudendal Nerve Prior to Sacrospinous Ligament Suspension.
	No Results Available Procedure: Pudendal nerve block|Procedure: Sham Pudendal nerve block|Drug: Bupivacaine Injectable Product Post-operative Pain Score|Readiness for discharge|Patient satisfaction|Functional Recovery Index|Post-operative Analgesic use Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Care Provider)|Primary Purpose: Treatment FHREB2020-143 June 2022

Health, N. Y. U. L. (2022). The Using Postoperative Ketamine and Exploring the Effect on Endometriosis Pain (UPKEEEP) Study.
	This is a randomized, single blinded, placebo-controlled trial to study the effectiveness of a subanesthetic dose (0.6 mg/kg) of ketamine versus placebo (saline) on postoperative pain and pain on adult female chronic pelvic pain patients undergoing robotic removal of endometriosis. The objective of the study is to explore the effect of a sub anesthetic dose of ketamine (0.6 mg/kg) vs. saline control on postoperative pain and recovery in chronic pelvic pain patients who have undergone robotic removal of endometriosis. Primary Outcome: Pelvic Pain

Heer, K., et al. (2024). "Prevalence, Risk Factors, and Interventions of Postpartum Depression in Refugees and Asylum-Seeking Women: A Systematic Review and Meta-Analysis." Gynecologic and Obstetric Investigation 89(1): 11-21.
	Introduction: Refugee women are at an increased risk of developing postpartum depression (PPD) due to a combination of various psychosocial stressors. This systematic review aimed to outline the prevalence of PPD among refugee women and explore related risk factors and interventions currently in practice. Method(s): A search was conducted using MEDLINE, Embase, PsycINFO, CINAHL, and Core Collection (Web of Science) for articles published until August 2022, yielding 1,678 records. Result(s): The prevalence of refugee and asylum-seeking women was 22.5% (n = 657/ 2,922), while the prevalence of non-refugee/asylum-seeking women with PPD was 17.5% (n = 400/2,285). Refugee/ asylum-seeking women face a unique set of issues such as domestic abuse, separation and lack of support, stress, pre-migrational experiences, prior history of mental illness, low income, and discrimination. Refugee/asylum-seeking women may benefit from support groups, individual support, self-coping mechanisms, and familial support. Conclusion(s): This review identifies that a higher prevalence of PPD in refugee and asylum-seeking women compared to other groups can potentially be attributed to the unique risk factors they face. This warrants the need for further research as studies on interventions for this condition are limited among this population.Copyright © 2024 The Author(s). Published by S. Karger AG, Basel.

Heidari, H., et al. (2022). "A meta-analysis of effects of vitamin E supplementation alone and in combination with omega-3 or magnesium on polycystic ovary syndrome." Scientific Reports 12(1): 19927.
	Vitamin E supplementation might have favorable effects on risk factors of polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to summarize the effects of vitamin E supplementation or vitamin E in combination with omega-3 or magnesium on PCOS. PubMed, Scopus, ISI Web of Science, Cochrane, Embase electronic databases, and Google scholar were searched for all available articles up to September 2022. Randomized controlled trials (RCTs) that examined the effect of vitamin E supplementation or vitamin E in combination with omega-3 or magnesium on lipid and glycemic profiles, anthropometric measurements, biomarkers of inflammation and oxidative stress, hormonal profile, and hirsutism score in patients with PCOS were included. Ten RCTs (with 504 participants) fulfilled the eligible criteria. Vitamin E supplementation or vitamin E in combination with omega-3 or magnesium in comparison to placebo could significantly reduce serum levels of TG (weighted mean difference: - 18.27 mg/dL, 95% CI - 34.68 to - 1.87), VLDL (- 5.88 mg/dL, 95% CI - 8.08 to - 3.68), LDL-c (- 12.84 mg/dL, 95% CI - 22.15 to - 3.52), TC (- 16.30 mg/dL, 95% CI - 29.74 to - 2.86), TC/HDL-c ratio (- 0.52, 95% CI - 0.87 to - 0.18), hs-CRP (- 0.60 ng/mL, 95% CI - 0.77 to - 0.44), hirsutism score (- 0.33, 95% CI - 0.65 to - 0.02) and significantly increase nitric oxide levels (2.79 µmol/L, 95% CI 0.79-4.79). No significant effect was found on HDL-c, glycemic indices, hormonal profile, anthropometric measurements, and other biomarkers of inflammation or oxidative stress. This meta-analysis highlights the potential anti-hyperlipidemic, anti-oxidant, and anti-inflammatory properties of vitamin E supplementation alone or in combination with omega-3 or magnesium on PCOS patients. (© 2022. The Author(s).)

Heidinger, M., et al. (2023). "Therapeutic approaches in patients with bone metastasis due to endometrial carcinoma - A systematic review." Journal of bone oncology 41: 100485.
	Background: Bone metastases (BM) are uncommon in endometrial carcinoma (EC), without information on the optimal oncologic management of patients with BM in EC. Here, we systematically review clinical characteristics, treatment approaches and prognosis in patients with BM in EC.; Methods: We conducted a systematic literature search until 27th March 2022 on PubMed, MEDLINE, Embase and clinicaltrials.gov. Outcomes included treatment frequency and survival after BM with comparators being treatment approaches (local cytoreductive bone surgery, systemic therapy, and local radiotherapy). Risk of bias was assessed using the NIH Quality Assessment Tool and Navigation Guide methodology.; Results: We retrieved 1096 records of which 112 retrospective studies (12 cohort studies, 12/12 fair quality; 100 case studies, 100/100 low quality) with a total of 1566 patients were included. The majority had a primary diagnosis of FIGO stage IV, grade 3 endometrioid EC. Singular BM were present in a median of 39.2%, multiple BM in 60.8% and synchronous additional distant metastases in 48.1% of patients respectively. In patients with secondary BM median time to bone recurrence was 14 months. Median survival after BM was 12 months. Local cytoreductive bone surgery was assessed in 7/13 cohorts and performed in a median of 15.8% (interquartile range [IQR] 10.3-43.0) of patients. Chemotherapy was assessed in 11/13 cohorts and administered in a median of 55.5% (IQR 41.0-63.9), hormonal therapy (7/13 cohorts) in 24.7% (IQR 16.3-36.0), and osteooncologic therapy (4/13 cohorts) in 2.7% (IQR 0.0-7.5) of patients respectively. Local radiotherapy was assessed in 9/13 cohorts and performed in a median of 66.7% (IQR 55.6-70.0) of patients. Survival benefits were seen in 2/3 cohorts after local cytoreductive bone surgery, and in 2/7 cohorts after chemotherapy without survival benefits in the remaining cohorts and investigated therapies. Limitations include the lack of controlled intervention studies, the heterogeneity and retrospective nature of the investigated populations.; Conclusions: This systematic review shows heterogenous therapeutic approaches in clinical practice without clear evidence for optimal oncologic management for patients with BM in EC.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Author(s).)

Heinemeier Ina Isabell, K., et al. (2023). "Impact of combined endometrial resection or ablation and levonorgestrel intrauterine device on postoperative bleeding pattern." Archives of Gynecology and Obstetrics 307(2): 493-499.
	Purpose: The aim of this study was to describe the rate of amenorrhea in women treated with transcervical endometrial resection (TCER) or radiofrequency endometrial ablation combined with levonorgestrel intrauterine contraceptive device (LNG-IUD) six months post-operatively.; Methods: The study was performed as a prospective cohort study. All patients were included at four gynecological centers in Region of Southern Denmark. In total, 162 women referred due to menorrhagia, metrorrhagia or menometrorrhagia and offered TCER or radiofrequency endometrial ablation in combination with or without LNG-IUD included during November 2018 to June 2021 at the women's own discretion and without any cost (covered by the hospital). Data were analyzed using a multivariate regression model.; Results: In total, 58 women were offered TCER and 31 (53.4%) combined treatment with TCER + LNG-IUD. Among 104 women who received radiofrequency endometrial ablation, 46 (44.2%) underwent combined treatment with LNG-IUD. The incidence of amenorrhea was 26% among women who underwent treatment with TCRE and 52% when treated with TCER + LNG-IUD (adjusted OR 5.16; 95% CI 1.35-19.6; P < 0.016). Radiofrequency endometrial ablation was followed by a 41% incidence of amenorrhea, and when radiofrequency endometrial ablation was combined with LNG-IUD, the incidence of amenorrhea was 63% (adjusted OR 2.15; 95% CI 0.86-5.37; P < 0.1). We observed no statistically significant differences when comparing the groups across.; Conclusion: Our study suggests that the combination of TCER or radiofrequency endometrial ablation with LNG-IUD was superior to TCER. However, the combined treatment of radiofrequency endometrial ablation with LNG-IUD did not reach statistical significance. Further studies are needed to evaluate the effects of different ablation techniques on the amenorrhea rate. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Heinz-Partington, S., et al. (2021). "Conservative vs radical bowel surgery for endometriosis: A systematic analysis of complications." The Australian & New Zealand Journal of Obstetrics & Gynaecology 61(2): 169-176.
	Background: Endometriosis of the bowel can be associated with significant morbidity. Surgery to remove it carries risks. Options include conservative shaving or discoid resection and more radical segmental bowel resection.; Aims: To determine if more conservative shaving or discoid bowel resection is associated with fewer risks than more radical segmental resection.; Material and Methods: This study is a systematic review. We considered eligible any cohort, observational or randomised controlled trial (RCT) study of at least ten women per arm comparing conservative vs radical bowel surgery for endometriosis. We divided complications into two groups, major and minor. One additional article was added due to its significance in answering our study question as well as the high quality of the study design as an RCT.; Results: There were 3041 studies screened. Eleven studies were included (n = 1648). For major complications, the risk ratio for shaving and disc excision vs segmental resection is 0.31 (95% CI 0.21-0.46), while the risk difference is -0.25 (95% CI -0.41 to 0.10). For minor complications, the risk ratio is 0.63 (95% CI 0.36-1.09), while the risk difference is -0.03 (95% CI -0.12 to 0.05).; Conclusions: Conservative shaving or discoid excision surgery is associated with reduced complications. Previous studies demonstrated a trend toward this finding, but suffered from relatively low participant numbers, increasing the risk of type one statistical error. Our results allow surgeons to make informed choices about potential complications when deciding how to approach bowel endometriosis. The results also allow patients to have more information about the risks. However, outcomes in the studies analysed are heterogenous and are from low-quality evidence. (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Heitz, N., et al. (2023). "A Review of Tisotumab Vedotin-tftv in Recurrent or Metastatic Cervical Cancer." The Annals of Pharmacotherapy 57(5): 585-596.
	Objective: To evaluate the safety and efficacy of tisotumab vedotin-tftv (TV), a first-in-class vectorized anti-tissue factor (TF) antibody-drug conjugate (ADC), for the treatment of recurrent or metastatic cervical cancer.; Data Sources: A literature search of ClinicalTrials.gov, Embase, and PubMed was conducted using the terms tisotumab vedotin AND cervical cancer from inception to June 30, 2022.; Study Selection and Data Extraction: All applicable publications, package inserts, meeting abstracts, and clinical trials involving TV in the treatment of cervical cancer were reviewed.; Data Synthesis: TV is a fully human TF-specific monoclonal antibody conjugated to monomethyl auristatin E, which serves as a highly potent cytotoxic payload. In the pivotal phase II InnovaTV 204 clinical trial, TV demonstrated an objective response rate of 24% (95% confidence interval [CI], 16%-33%). The mean duration of response was 8.3 months. Common toxicities included abdominal pain, alopecia, conjunctivitis, constipation, decreased appetite, diarrhea, dry eye, epistaxis, nausea/vomiting, and peripheral neuropathy. Unique and/or serious adverse events warranting careful monitoring include ocular complications, hemorrhaging, peripheral neuropathies, fetal-embryo toxicity, pneumonitis, and immunogenicity.; Relevance to Patient Care and Clinical Practice: Recurrent or metastatic cervical cancer remains a high-risk disease with limited treatment options. Using ADCs to target tumors with aberrant expression of TF appears to be a viable treatment strategy.; Conclusions: TV is the first Food and Drug Administration-approved TF-directed ADC. With a manageable safety profile and promising anticancer activity, TV warrants consideration as a novel targeted agent for the treatment of recurrent or metastatic cervical cancer. Further studies are required to determine the optimal place in therapy for TV.

Helgers, R. J. A., et al. (2021). "Lymphedema and post-operative complications after sentinel lymph node biopsy versus lymphadenectomy in endometrial carcinomas-a systematic review and meta-analysis." Journal of Clinical Medicine 10(1): 1-16.
	Background: Lymph node dissection (LND) is recommended as staging procedure in presumed low stage endometrial cancer. LND is associated with risk of lower-extremity lymphedema and post-operative complications. The sentinel lymph node (SLN) procedure has been shown to have high diagnostic accuracy, but its effects on complication risk has been little studied. This systematic review compares the risk of lower-extremity lymphedema and post-operative complications in SLN versus LND in patients with endometrial carcinoma. Method(s): A systematic search was conducted in PubMed and Cochrane Library. Result(s): Seven retrospective and prospective studies (total n = 3046 patients) were included. Only three studies reported the odds ratio of lower-extremity lymphedema after SLN compared to LND, which was 0.05 (95% CI 0.01-0.37; p = 0.067), 0.07 (95% CI 0.00-1.21; p = 0.007) and 0.54 (95% CI 0.37-0.80; p = 0.002) in these studies. The pooled odds ratio of any post-operative complications after SLN versus LND was 0.52 (95% CI 0.36-0.73; I2 = 48%; p < 0.001). For severe post-operative complications the pooled odds ratio was 0.52 (95% CI 0.28-0.96; I2 = 0%; p = 0.04). Conclusion(s): There are strong indications that SLN results in a lower incidence of lower-extremity lymphedema and less often severe post-operative complications compared to LND. In spite of the paucity and heterogeneity of studies, direction of results was similar in all studies, supporting the aforementioned conclusion. These results support the increasing uptake of SLN procedures in endometrial cancer.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Hellier Susan, D. and F. Wrynn Alexander (2023). "Beyond fluconazole: A review of vulvovaginal candidiasis diagnosis and treatment." The Nurse practitioner 48(9): 33-39.
	Abstract: Vaginitis symptoms are among the most common reasons for patients to seek acute gynecological care. NPs who care for women and other patients with vaginas need to be up-to-date on diagnosis and treatment of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Two new antifungal medications for VVC are available. This article reviews vaginal physiology and provides an overview of VVC and RVVC pathophysiology, diagnosis, and treatment options. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Helm, S., et al. (2021). "Peripheral Nerve Stimulation for Chronic Pain: A Systematic Review of Effectiveness and Safety." Pain and therapy 10(2): 985-1002.
	Peripheral nerve stimulation (PNS) was the first application of neuromodulation. Widespread application of PNS was limited by technical concerns. Recent advances now allow the percutaneous placement of leads with ultrasound or fluoroscopic guidance, while the transcutaneous powering of these leads removes the need for leads to cross major joints. This systematic review was written to assess the current status of high-quality evidence supporting the use of PNS for pain conditions treated by interventional pain physicians. The available literature on PNS, limited to conditions treated by interventional pain physicians, was reviewed and the quality assessed. Literature from 1966 to June 2021 was reviewed. The outcome measures were pain relief and functional improvement. One hundred and two studies were identified. Five randomized controlled trials (RCT) and four observational studies, all case series, met the inclusion criteria. One RCT was of high quality and four were of moderate quality; all four case series were of moderate quality. Three of the RCTs and all four case series evaluated peripheral nerve neuropathic pain. Based upon these studies, there is level II evidence supporting the use of PNS to treat refractory peripheral nerve injury. One moderate-quality RCT evaluated tibial nerve stimulation for pelvic pain, providing level III evidence for this indication. One moderate-quality RCT evaluated surgically placed cylindrical leads for cluster headaches, providing level III evidence for this indication. The evidence suggests that approximately two-thirds of patients with peripheral neuropathic pain will have at least 50% sustained pain relief. Adverse events from PNS are generally minor. A major advantage of PNS over spinal cord stimulation is the absence of any risk of central cord injury. The study was limited by the paucity of literature for some indications. No studies dealt with joint-related osteoarthritic pain. (© 2021. The Author(s).)

Hemmerling, A., et al. (2023). "Response to antibiotic treatment of bacterial vaginosis predicts the effectiveness of LACTIN-V (Lactobacillus crispatus CTV-05) in the prevention of recurrent disease." MedRxiv.
	Objectives: Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment. Method(s): A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 FDA guidance) two days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks. Result(s): At enrollment, 88% of participants had achieved clinical BV cure. The effect of LACTIN-V on BV recurrence compared to placebo differed by initial clinical BV cure status (p=0.02 by 12 weeks, and p=0.08 by 24 weeks). The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (CI: 0.35, 0.77) among participants with initial clinical BV cure, and 1.34 (CI: 0.47, 2.23) among participants without clinical BV cure. Among women receiving LACTIN-V, those who had achieved clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared to women failing to achieve clinical BV cure. Conclusion(s): LACTIN-V appears to only decrease BV recurrence in women with clinical cure of BV following antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Hend, H., et al. (2022). "Long term outcomes of hysterectomy and bilateral salpingo-oophorectomy: a systematic review and meta-analysis."
	
Hendrickson, W. K., et al. (2021). "Comparison of 100 U With 200 U of Intradetrusor OnabotulinumToxinA for Nonneurogenic Urgency Incontinence." Female Pelvic Medicine & Reconstructive Surgery 27(3): 140‐146.
	OBJECTIVES: The objective of this study was to compare efficacy and adverse events between 100 U and 200 U of onabotulinumtoxinA for 6 months in women with nonneurogenic urgency incontinence. METHODS: This is a secondary analysis of 2 multicenter randomized controlled trials assessing efficacy of onabotulinumtoxinA in women with nonneurogenic urgency incontinence; one compared 100 U to anticholinergics and the other 200 U to sacral neuromodulation. Of 307 women who received onabotulinumtoxinA injections, 118 received 100 U, and 189 received 200 U. The primary outcome was mean adjusted change in daily urgency incontinence episodes from baseline over 6 months, measured on monthly bladder diaries. Secondary outcomes included perceived improvement, quality of life, and adverse events. The primary outcome was assessed via a multivariate linear mixed model. RESULTS: Women receiving 200 U had a lower mean reduction in urgency incontinence episodes by 6 months compared with 100 U (‐3.65 vs ‐4.28 episodes per day; mean difference, 0.63 episodes per day [95% confidence interval (CI), 0.05‐1.20]). Women receiving 200 U had lower perceptions of improvement (adjusted odds ratio, 0.32 [95% CI, 0.14‐0.75]) and smaller improvement in severity score (adjusted mean difference, 12.0 [95% CI, 5.63‐18.37]). Upon subanalysis of only women who were treated with prior anticholinergic medications, these differences between onabotulinumtoxinA doses were no longer statistically significant. There was no statistically significant difference in adverse events in women receiving 200 U (catheterization, 32% vs 23%; adjusted odds ratio, 1.4 [95% CI, 0.8‐2.4]; urinary tract infection, 37% vs 27%; adjusted odds ratio, 1.5 [95% CI, 0.9‐2.6]). CONCLUSIONS: A higher dose of onabotulinumtoxinA may not directly result in improved outcomes, but rather baseline disease severity may be a more important prediction of outcomes.

Hendrix, Y. M. G. A., et al. (2021). "Postpartum Early EMDR therapy Intervention (PERCEIVE) study for women after a traumatic birth experience: study protocol for a randomized controlled trial." Trials 22(1): 599.
	Background: Up to 33% of women develop symptoms of posttraumatic stress disorder (PTSD) after a traumatic birth experience. Negative and traumatic childbirth experiences can also lead to fear of childbirth, avoiding or negatively influencing a subsequent pregnancy, mother-infant bonding problems, problems with breastfeeding, depression and reduced quality of life. For PTSD in general, eye movement desensitization and reprocessing (EMDR) therapy has proven to be effective. However, little is known about the preventive effects of early intervention EMDR therapy in women after a traumatic birth experience. The purpose of this study is to determine the effectiveness of early intervention EMDR therapy in preventing PTSD and reducing PTSD symptoms in women with a traumatic birth experience.; Methods: The PERCEIVE study is a randomized controlled trial. Women suffering from the consequences of a traumatic birth experience will be randomly allocated at maximum 14 days postpartum to either EMDR therapy or 'care-as-usual'. Patients in the EMDR group receive two sessions of therapy between 14 (T0) and 35 days postpartum. All participants will be assessed at T0 and at 9 weeks postpartum (T1). At T1, all participants will undergo a CAPS-5 interview about the presence and severity of PTSD symptoms. The primary outcome measure is the severity of PTSD symptoms, whereas the secondary outcomes pertain to fear of childbirth, mother-infant bonding, breastfeeding, depression and quality of life. The study will be conducted at a large city hospital and at multiple midwifery practices in Amsterdam, the Netherlands.; Discussion: It is to be expected that the results of this study will provide more insight about the safety and effectiveness of early intervention EMDR therapy in the prevention and reduction of PTSD (symptoms) in women with a traumatic birth experience.; Trial Registration: Netherlands Trial Register NL73231.000.20 . Registered on 21 August 2020. (© 2021. The Author(s).)

Hengxi, C. and H. Lin (2023). "Minimally invasive radical trachelectomy versus abdominal radical trachelectomy for early-stage cervical cancer: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Henkel, A., et al. (2023). "Cabergoline for Lactation Inhibition After Second-Trimester Abortion or Pregnancy Loss: A Randomized Controlled Trial." Obstetrics and Gynecology 141(6): 1115-1123.
	Objective: To assess cabergoline's efficacy at decreasing breast symptoms after second-trimester abortion or pregnancy loss.; Methods: This was a double-blinded, block-randomized superiority trial comparing cabergoline 1 mg once to placebo for preventing bothersome breast engorgement after second-trimester uterine evacuation. We enrolled pregnant people at 18-28 weeks of gestation who were English- or Spanish-speaking and without contraindication to the study drug. Participants completed a validated, piloted, electronic survey at baseline and at multiple timepoints through 2 weeks postprocedure to assess breast symptoms, side effects, and bother. Our primary outcome was any breast symptoms (a composite of engorgement, milk leakage, tenderness, and need for pain relief) on day 4; we planned to enroll 80 patients to show a 30% difference in breast symptoms (80% power, α=0.049). A subgroup of participants returned for serum prolactin levels.; Results: After screening 150 patients from April 2021 to June 2022, we enrolled 73 participants. Baseline demographics were balanced between groups: median gestational age was 21 weeks (range 18-26 weeks), 56.2% of participants were nulliparous, 34.2% self-identified as Hispanic, and 37.0% had public insurance. At baseline, reported breast symptoms were similar between groups. Among 69 participants who returned surveys on day 4, significantly fewer participants receiving cabergoline reported any breast symptoms compared with placebo (27.8% vs 97.0%, P<.001) (primary outcome) and fewer reported significant bother (2.8% vs 33.3%, P=.001) (secondary outcome). These differences persisted through day 14. Reported incidence and severity of bother from side effects were similar between groups: most common were constipation, fatigue, and headache. Serum prolactin levels were similar at baseline. On day 4, mean serum prolactin level was 6.5 ng/mL (SD 2.2) for those who received cabergoline and 18.0 ng/mL (SD 5.9) for placebo (P=.049).; Conclusion: Cabergoline is an effective and well-tolerated strategy to prevent breast symptoms after second-trimester abortion or pregnancy loss.; Clinical Trial Registration: ClinicalTrials.gov, NCT04701333.; Competing Interests: Financial Disclosure This article discusses off-label use of cabergoline. Matthew F. Reeves reports receiving payments from GemBioPro (distributor of mifepristone, unrelated to cabergoline). The other authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Hensler, M., et al. (2022). "Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines." Oncoimmunology 11(1): 2101596.
	Dendritic cells (DCs) have received considerable attention as potential targets for the development of novel cancer immunotherapies. However, the clinical efficacy of DC-based vaccines remains suboptimal, largely reflecting local and systemic immunosuppression at baseline. An autologous DC-based vaccine (DCVAC) has recently been shown to improve progression-free survival and overall survival in randomized clinical trials enrolling patients with lung cancer (SLU01, NCT02470468) or ovarian carcinoma (SOV01, NCT02107937), but not metastatic castration-resistant prostate cancer (SP005, NCT02111577), despite a good safety profile across all cohorts. We performed biomolecular and cytofluorometric analyses on peripheral blood samples collected prior to immunotherapy from 1000 patients enrolled in these trials, with the objective of identifying immunological biomarkers that may improve the clinical management of DCVAC-treated patients. Gene signatures reflecting adaptive immunity and T cell activation were associated with favorable disease outcomes and responses to DCVAC in patients with prostate and lung cancer, but not ovarian carcinoma. By contrast, the clinical benefits of DCVAC were more pronounced among patients with ovarian carcinoma exhibiting reduced expression of T cell-associated genes, especially those linked to T H2 -like signature and immunosuppressive regulatory T (T REG ) cells. Clinical responses to DCVAC were accompanied by signs of antitumor immunity in the peripheral blood. Our findings suggest that circulating signatures of antitumor immunity may provide a useful tool for monitoring the potency of autologous DC-based immunotherapy.; Competing Interests: IV declares consulting for AstraZeneca, Clovis Oncology Inc., Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, F. Hoffmann-La Roche Ltd, Genmab, GSK, Immunogen Inc., Jazzpharma, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Octimet Oncology NV, Oncoinvent AS, Sotio a.s., Verastem Oncology, Zentalis; contracted research for: Oncoinvent AS, Genmab; and research funding from Amgen and Roche. RS and JB are minority shareholders of Sotio. ADG received fees for consultancy, lectures or services from Boehringer Ingelheim (Germany), Miltenyi Biotec (Germany), Isoplexis (USA) and Novigenix (Switzerland). AR declares advisory services and invited lectures for Amgen, AstraZeneca, BMS, Eli-Lilly, Janssen-Cilag, MSD, and Roche. AC is a contracted researcher for Oncoinvent AS and Novocure and a consultant for Sotio Biotech a.s. MH, JR, LK, TL, JF, PH, MH, TH, PK, KS, DR, LS, JB, RS, and JF are employees of Sotio a.s. The other authors declare no conflicts of interest. (© 2022 Sotio Biotech. Published with license by Taylor & Francis Group, LLC.)

Heo, S. J., et al. (2023). "Effects of phytoncide on immune cells and psychological stress of gynecological cancer survivors: randomized controlled trials." Journal of exercise rehabilitation 19(3): 170-180.
	This study aimed to identify neuroendocrine substances and natural killer (NK) cells, including their subsets and receptors, to determine whether phytoncides scented in an urban hospital could help improve stress in cancer survivors. Fifty-five gynecological cancer survivors were assigned to either the control group (CG, n=28) or phytoncide group (PTG, n=27). The PTG meditated by lying down in a space scented with phytoncide for 1 hr a day, 5 days a week for 8 weeks. Stress levels in both groups were high prior to the experiment and decreased by 9.31%±45.98% (P=0.003) only in the PTG after the experiment. Although the parasympathetic nerve activity of the PTG increased, the epinephrine and cortisol levels were significantly (P<0.001) decreased by 5.29%±25.5% and by 24.94%±11.62%. Moreover, the PTG showed a significant increase in the levels of NK cell subsets after 8 weeks, whereas there was no improvement in the CG. In conclusion, phytoncide fragrance reduces stress, increases the number of NK cells and their family even in a nonforest environment, and improves innate immunocytes in gynecological cancer survivors; parasympathetic nerve activity and cortisol hormones play critical roles in this process. That is, a phytoncide essential oil helps to stimulate changes in immunocytes' mobility by affecting the human nervous and endocrine systems, thereby providing relief for psychological stress among cancer survivors who previously had cancer cells.

Herbert, S. and K. Woolf (2023). "Moving beyond Weight: A Narrative Review of the Dietary and Lifestyle Management for Reducing Cardiometabolic Risk in Polycystic Ovary Syndrome (PCOS)." Nutrients 15(24).
	Polycystic ovary syndrome (PCOS) is the most common endocrine disorder experienced by women. PCOS is a lifelong condition associated with reproductive, metabolic, and psychological presentations. PCOS is also linked with increased prevalence of cardiometabolic risk factors. While an association between body weight and PCOS has been noted, cardiometabolic risk factors are prevalent in individuals with PCOS across body weights. Currently, no consensus exists as to the most appropriate lifestyle strategy for mitigating cardiometabolic risk in PCOS. A large proportion of the literature is focused on weight loss for individuals with PCOS who are overweight or experience obesity, despite PCOS being prevalent across body sizes. The aim of this narrative review is to assess dietary and lifestyle interventions aimed at reducing cardiometabolic risk in individuals with PCOS across body sizes. A total of 51 articles are included in this review. Overall, randomized controlled trials are limited and most studies focus on weight loss, excluding individuals classified within a healthy body weight range. Studies that modified the dietary pattern without an energy deficit saw improvements in cardiometabolic risk. Thus, less restrictive dietary approaches may be effective at reducing cardiometabolic risk in this population. This review also highlights the need for more sustainable lifestyle interventions that meet the needs of individuals with PCOS of varying body weights.

Herlev Copenhagen University Hospital, a., et al. (2021). Estradiol and Progestrone Levels Following Frozen Embryo Transfer.
	No Results Available Drug: Estradiol Tablets|Drug: Progesterone|Drug: Follitropin Alfa|Drug: Chorionic Gonadotropin, Alpha Serum estradiol|Serum progesterone|Gestational age at delivery|Child birth weight|Obstetric complications|Child malformations Female Phase 4 300 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Health Services Research 2020-001218-39 December 2024

Hernández Alberto, V., et al. (2022). "Ghost Ileostomy: Safe and Cost-effective Alternative to Ileostomy After Rectal Resection for Deep Infiltrating Endometriosis." In vivo (Athens, Greece) 36(3): 1290-1296.
	Background/aim: Endometriosis infiltrating the rectum often requires resection with a protecting stoma. A ghost ileostomy (GI) is an alternative to prevent the psychological burden for the young women affected. The present study evaluated the safety and cost-effectiveness of the ghost ileostomy (GI) procedure in a group of patients after rectal resection for deep infiltrating endometriosis.; Patients and Methods: The prospective controlled interventional trial was conducted in 54 consecutive patients with deep infiltrating endometriosis of the rectum. GI was considered after ultra-low resection with primary anastomosis, previous colorectal anastomosis, or pelvic redo surgery. Loop ileostomy (LI) was performed after simultaneous colpotomy with suture, only. Operating time, morbidity according to the Clavien-Dindo classification (CDC), duration of hospital stay, and patient satisfaction were obtained. Individual costs were estimated for the endometriosis procedure with or without a GI or LI, including stoma supply and closure expenses.; Results: Of the 54 patients, 27 received GI (50%), whereas 4 underwent LI (7%). The remaining 23 patients received no outlet (NO). The complication rate did not differ among the GI, LI, and NO groups. Two cases were re-operated and required a diverting stoma, one in the GI and the NO group each. The additional healthcare expenses for each patient receiving a LI averaged 6,000 €. The patients were very satisfied with the option of a GI.; Conclusion: GI is a cost-effective and safe alternative to LI after rectal resection for deep infiltrating endometriosis in cases where it is required. The individual costs per patient were reduced substantially, with a cumulative savings of 160,000 € in healthcare expenditure. Additionally, the method clearly lowers the psychological burden on the young women concerned. (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hernandez, M., et al. (2021). "A multicenter clinical study with myo-inositol and alpha-lactalbumin in Mexican and Italian PCOS patients." European Review for Medical and Pharmacological Sciences 25(8): 3316-3324.
	- OBJECTIVE: This open-label non-randomized clinical study aimed at evaluating the effects of myo-inositol plus alpha-lactalbumin in two groups of PCOS women, treated in Mexico and Italy. Alpha-lactalbumin was used being effective in increasing myo-inositol intestinal absorption. This effect is very useful in greatly reducing the therapeutic failure of myo-inositol in some patients (inositol resistant subjects). PATIENTS AND METHODS: The study involved 34 normal weight or overweight patients (14 in Mexico and 20 in Italy), aged 18 to 40 years, with anovulation and infertility > 1 year and insulin resistance diagnosed by HOMA-Index. Patients were administered orally with 2 g myo-inositol, 50 mg alpha-lactalbumin, and 200 microg of folic acid twice a day for 6 months. Controls were the same patients at t0 (baseline). The primary outcome was HOMA-index decrease after 3 and 6 months of treatment. Other parameters monitored were BMI, progesterone, LH, FSH, total testosterone, free testosterone, androstenedione, total cholesterol, HDL, LDL, triglycerides. RESULT(S): Recovery was general, and its relevance was higher when the starting point was further away from the normal range. The most important results were obtained with insulin, HOMA-index, LH, and androstenedione. No significant adverse effects were detected in both groups of patients. CONCLUSION(S): This clinical trial demonstrated for the first time that myo-inositol and alpha-lactalbumin improve important parameters in PCOS patients characterized by different metabolic profiles.Copyright © 2021 Verduci Editore s.r.l. All rights reserved.

Hernandez-Aranda, D., et al. (2023). "Analgesia Using Transcutaneous Electric Nerve Stimulation in Office Bladder Chemodenervation, a Randomized Controlled Trial." Urogynecology (Philadelphia, Pa.).
	IMPORTANCE: Office bladder chemodenervation, performed via cystoscopy with intradetrusor onabotulinumtoxinA (BOTOX) injections, is a common treatment for overactive bladder/urge urinary incontinence. Transcutaneous electric nerve stimulation (TENS) has shown to provide analgesia during office hysteroscopy. Adjuvant analgesia using TENS during bladder chemodenervation has not been studied. OBJECTIVE(S): The primary outcome is a clinically significant (10-mm) difference in pain visual analog scale (VAS) measurements during injections for chemodenervation using active TENS compared with placebo TENS. We hypothesize that active TENS use will significantly change pain VAS scores. Secondary outcomes include 5-point pain Likert scale, satisfaction 10-point scale, and adverse events. STUDY DESIGN: This was a double-blind randomized control trial of men and women with urinary urge incontinence undergoing office chemodenervation performed in an academic and private setting. Participants were randomized into 2 groups: chemodenervation with active TENS or placebo TENS. Power calculation determined 100 patients would be required detect a difference of 10 mm on pain VAS. RESULT(S): One hundred one (85 female and 16 male) participants were recruited. No differences were noted in the demographics. Participants in the active TENS group reported a difference of greater than 10 mm in pain VAS scores (48 +/- 23 vs 31 +/- 23, P = 0.01). Satisfaction index scores were high but no difference was noted between groups (8.6 vs 8.7, P = 0.68). CONCLUSION(S): Most participants were eligible to use TENS units. Transcutaneous electric nerve stimulation is a safe and noninvasive adjuvant analgesia option for patients undergoing this procedure. Lower pain levels and high satisfaction rates suggest that this is an additional analgesic option during outpatient chemodenervation.Copyright © 2023 American Urogynecologic Society. All rights reserved.

Herzog Thomas, J. (2022). "Maintenance therapy with PARP inhibition in ovarian cancer." Clinical advances in hematology & oncology : H&O 20(9): 539-541.
	
Herzog Thomas, J., et al. (2023). "Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA/ENGOT-ov26/GOG-3012 trial: challenges and solutions." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(11): 1733-1742.
	Objective: Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial designs. We compared blinded independent centralized review and investigator-assessed progressive disease performance in the PRIMA/ENGOT-ov26/GOG-3012 trial examining niraparib monotherapy.; Methods: PRIMA/ENGOT-ov26/GOG-3012 was a randomized, double-blind phase 3 trial; patients with newly diagnosed stage III/IV ovarian cancer received niraparib or placebo. The primary endpoint was progression-free survival (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), determined by two independent radiologists, an arbiter if required, and by blinded central clinician review. Discordance rates between blinded independent centralized review and investigator assessment of progressive disease and non-progressive disease were routinely assessed. To optimize disease assessment, a training intervention was developed for blinded independent centralized radiological reviewers, and RECIST refresher training was provided for investigators. Discordance rates were determined post-intervention.; Results: There was a 39% discordance rate between blinded independent centralized review and investigator-assessed progressive disease/non-progressive disease in an initial patient subset (n=80); peritoneal carcinomatosis was the most common source of discordance. All reviewers underwent training, and as a result, changes were implemented, including removal of two original reviewers and identification of 10 best practices for reading imaging data. Post-hoc analysis indicated final discordance rates between blinded independent centralized review and investigator improved to 12% in the overall population. Median progression-free survival and hazard ratios were similar between blinded independent centralized review and investigators in the overall population and across subgroups.; Conclusion: PRIMA/ENGOT-ov26/GOG-3012 highlights the need to optimize blinded independent centralized review and investigator concordance using early, specialized, ovarian-cancer-specific radiology training to maximize validity of outcome data.; Competing Interests: Competing interests: TJH has served on advisory boards (Aravive, AstraZeneca, Caris, Clovis Oncology, Eisai, Epsilogen, GSK, Immunogen, Johnson & Johnson, Merck, Roche Genentech, Seagen) and as a consultant for Abbvie. SAW reports consulting fees (GSK and BioClinica). MRM reports personal fees and other (Karyopharm Therapeutics, Sera Prognostics, Roche); institutional grants and no financial interest (Apexigen, AstraZeneca, Deciphera, GSK, Ultimovacs); personal fees and invited speaker (AstraZeneca, GSK); personal fees and advisory boards (AstraZeneca, Biocad, Boehringer Ingelheim, GSK, Karyopharm, Merck, Mersana, ImmunoGen, Clovis Oncology, Roche, Zailab); personal fees, stocks and a member of board of directors (Karyopharm). BP reports research funding (AstraZeneca, Celgene, Celsion, Clovis, Genentech, SeaGen, GSK, Merck, Mersana, SeaGen, Takada, Toray) and consulting fees (AstraZeneca, Celsion, Eisai, GSK, GOG Foundation, Immunogen, Inxmed, Lily, Merck, Mersana, SeaGen, Toray). IV reports consulting fees (Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncoXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis), travel grants (Karyopharm, Genmab, Novocure), and contracted research grants (Amgen, Roche, Oncoinvent AS). WSG reports advisory board and speaker fees (GSK). IAM, WY, and DG are employees of GSK. JAH is an employee of GSK and reports stocks in GSK. AGM reports personal fees for educational/advisory-related activities (Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Immunogen, Mersana, MSD, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, Takeda). BJM repor s consulting fees (Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyoparm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, GSK, US Oncology Research, VBL, Verstem, Zentalis); speakers honoraria (AstraZeneca, Clovis, Eisai, Merck, Myriad, Roche/Genentech, GSK); investigator honoraria (Gradalis). (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Heshmati, J., et al. (2019). "The Effects of Probiotics or Synbiotics Supplementation in Women with Polycystic Ovarian Syndrome: a Systematic Review and Meta-Analysis of Randomized Clinical Trials." Probiotics and Antimicrobial Proteins 11(4): 1236-1247.
	We searched bibliographic databases from inception through May 2018 to evaluate the effect of probiotics (or synbiotics) supplementation in women suffering from polycystic ovary syndrome (PCOS). Seven trials involving 236 women with PCOS and 235 controls were included in the meta-analysis. Comparing with the control group, probiotics (or synbiotics) may improve Quantitative insulin sensitivity check index (QUICKI) (standardized mean difference (SMD) 0.41, 95% confidence intervals (CI) 0.01 to 0.82, P = 0.04), decrease triglyceride (TG) level (mean difference (MD) - 17.51 mg/dL, 95% CI - 29.65 to - 5.36); fasting insulin: (MD - 2.14 μIU/mL, 95% CI - 4.24 to - 0.04), and increase high-density lipoprotein (HDL) (SMD 1.55 mg/dL, 95% CI 0.28 to 2.81). No significant effect of probiotics (or synbiotics) on homeostatic model assessment-insulin resistance (HOMA-IR), fasting plasma glucose (FPG), low-density lipoprotein (LDL), total cholesterol (TC), and anthropometric indices was found in women with PCOS. Although probiotic (or synbiotics) supplementation was effective on some metabolic indices, the effect was negligible and not clinically significant.

Hess, E., et al. (2021). "Internet-based treatment for vulvodynia (EMBLA) - Study protocol for a randomised controlled study." Internet interventions 25: 100396.
	Background: Vulvodynia is defined as vulvar pain for at least 3 months without a clear cause. To the best of our knowledge, there are no trials investigating the effects of internet treatment using CBT (Cognitive behavioural therapy) treatment with Acceptance and Commitment Therapy (ACT) components for women with vulvodynia. The aim of this study is to examine the effects of such a guided internet-based intervention on provoked vulvar pain during the waiting period before clinical treatment.; Methods: We will randomise 52 patients to either guided internet-based intervention with CBT with (ACT) components or no intervention during the waiting period for treatment as usual. Online assessments are conducted at baseline, posttreatment, and at follow-up after 9 months. The primary outcome measure is provoked vulvar pain. Secondary outcomes are depression, anxiety, sexual function, and quality of life. Linear-mixed effect models will be used to assess the effect of the internet-based intervention on vulvar pain, pain acceptance, depression, anxiety, sexual function, and quality of life over time, by applying the intention-to-treat approach. Continuous data will be analysed with general linear models using intention-to-treat and also per protocol approaches to assess the effects of the intervention at different time points. Ordinal and binary data will be analysed with Mann Whitney's test, Fischer's exact test and multivariate logistic regression, respectively.; Discussion: As a randomised controlled trial with short- and long-term follow-up points, the EMBLA study intends to provide a novel and better understanding regarding the treatment of vulvodynia and the role of internet-based treatment as a complement to standard care for women suffering from vulvodynia. The effects of vulvodynia on pain, sexual function, quality of life, depression, and anxiety are investigated. The study's results are expected to be of value in the planning of clinical care in the medical area. High dropout rates and technical difficulties associated with using the platform are common in similar studies.; Trial Registration Number: NCT02809612.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 The Author(s).)

Hewawasam, E., et al. (2020). "Assessing Whether Meditation Improves Quality of Life for Adolescent Girls With Polycystic Ovary Syndrome: Protocol for a Randomized Controlled Trial." JMIR Research Protocols 9(1): e14542.
	Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine condition characterized by irregular periods and hyperandrogenism. Adolescents with PCOS have impaired quality of life (QOL) and increased psychological distress. Transcendental Meditation (TM) is a well-established self-management strategy that has been used to improve stress and well-being. A meta-analysis of TM trials has shown beneficial effects on stress and blood pressure in adults. Recent data are suggesting that another self-management strategy called a mindfulness stress management program has a role in improving QOL in women with PCOS, but there are no studies in adolescents.; Objective: This study aims to evaluate the effect of TM on QOL and psychological distress in adolescent girls with PCOS.; Methods: This study is a randomized controlled trial that will be conducted over eight weeks at the Women's and Children's Hospital in Adelaide, South Australia, to determine the effect of TM on QOL and psychological distress in adolescent girls (aged 12-20 years) with PCOS. A total of 40 girls will be randomized into either the TM (n=20) or control group (n=20). The TM group will be asked to practice TM in a comfortable sitting position with the eyes closed, for 15 minutes twice daily over eight weeks. The control group will be asked to sit quietly for 15 minutes twice daily for eight weeks. The primary outcomes are any effects on improving QOL and psychological distress, and the secondary outcomes are any effects on lowering blood pressure and salivary cortisol levels.; Results: The recruitment of study participants began in May 2019 and is expected to be completed by June 2020. It is expected that the adolescent girls with PCOS practicing TM over eight weeks will have a significant improvement in QOL and psychological distress compared to adolescents in the control group. Also, it is expected that adolescent girls in the TM group will have lower salivary cortisol levels and lower blood pressure.; Conclusions: This study will be the first to evaluate the effect of TM on QOL in adolescent girls with PCOS. The study will provide valuable information on a potential self-management strategy to improve QOL and well-being in adolescent girls with PCOS.; Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN1261900019010; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376657&amp;isReview=true.; International Registered Report Identifier (irrid): PRR1-10.2196/14542. (©Erandi Hewawasam, Leah Brennan, Lynne Giles, Mary Louise Hull, Asha Short, Robert Norman, Alexia S Peña. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 28.01.2020.)

Hewett, R. (2022). "Effects of visceral manipulation treatment on women with infertility and adults with low back pain." Dissertation Abstracts International: Section B: The Sciences and Engineering 83(5-B): No-Specified.
	Background. Visceral manipulation (VM) is a manual therapy treatment approach applied to the abdominal region that focuses on releasing restrictions around the visceral tissue. There are many benefits of this treatment, ranging from improved digestion to improvement of women's health conditions, such as endometriosis. Over 6.7 million women currently struggle with the devastating effects of infertility worldwide. Current treatment options include hormone therapy, in-vitro fertilization (IVF), and acupuncture. These options tend to be expensive, carry a variety of short- and long-term health risks, and have not proven to always be effective. Current research suggests that many of the issues contributing to infertility are connected to restrictions within the fascia, scar tissue build-up, and lymphatic congestion. Therefore, we conducted a systematic review (SR) to synthesize the current research on VM. Our purpose was to determine if VM is a more effective treatment option than acupuncture in helping to increase rates of pregnancy in women struggling with infertility.Adult low-back pain (LBP) is a worldwide challenge that has led to a decrease in quality of life and physical activity as well as detrimental increases in health-related costs. Currently, the most common treatments for LBP are prescription medications and therapeutic exercise. However, even with the use of these treatments, there are still people who are unable to find relief from their pain, leading us to question what other treatments could be effective. Therefore, the purpose of the critically appraised topic (CAT) was to examine the current research in order to assess if VM is more effective than the current treatment options in assisting adults struggling with LBP. Methods. We conducted the search for the SR over five databases from May 2020 to January 2021. Two independent reviewers screened abstracts and full-text articles about this topic that included human female subjects and full-text articles in English. Exclusion criteria included articles that were not relevant, treatment options other than acupuncture and IVF, pilot studies, premature ovarian failure, and polycystic ovary syndrome. Two investigators independently rated the risk of bias using the PEDro and NIH-NHLBI tools.We conducted the search for the CAT from January 2010 to January 2021. Two independent reviewers screened the resulting articles about the topic that included human subjects, adults, and in English. Articles that included patients with pre-existing conditions or additional treatment options besides osteopathic manipulative treatment (OMT), VM, or therapeutic exercise were excluded from the results. Two investigators independently rated the risk of bias using the PEDro and NIH-NHLBI tools. P-values and confidence intervals are reported in this paper. Results. For the SR, there were a total 1,346 articles screened, and, of those, 152 full-text articles were assessed for eligibility, resulting in 11 articles included in the SR. The results of the SR revealed that VM could be a potential non-invasive treatment option for women struggling with infertility. Kramp (2012), Wurn et al. (2008), and Rice et al. (2015) assessed pregnancy rates after a manual therapy treatment program and showed significantly improved pregnancy rates.For the CAT, there were a total of 187 articles screened, and only three of those full-text articles were appraised. Tamer et al. (2017) and Licciardone and Gatchel (2020) revealed significant improvements in patients who received VM or OMT for their LBP (p < 0.05). Santos et al. (2019) also recorded improvements in LBP within the VM group. However, there was not significant differences in improvement when compared to the control. Conclusions. The results appeared to be promising for the use of VM. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Hiam, D., et al. (2019). "The effectiveness of high intensity intermittent training on metabolic, reproductive and mental health in women with polycystic ovary syndrome: study protocol for the iHIT- randomised controlled trial." Trials 20(1): 221.
	Background: Polycystic ovary syndrome (PCOS) is a reproductive-metabolic condition. Insulin resistance is a hallmark of PCOS and is related to increased hyperandrogenism that drives inherent metabolic, reproductive and psychological features of the syndrome. Insulin resistance in women with PCOS is managed by weight loss, lifestyle interventions (i.e. exercise, diet) and insulin-sensitising medications. This manuscript describes the protocol of our study evaluating the effectiveness of high intensity intermittent training (HIIT) or moderate intensity exercise on cardiometabolic, reproductive and mental health in overweight women with PCOS.; Methods/design: We will employ a three arm, parallel-group, randomised controlled trial recruiting 60 women diagnosed with PCOS, aged between 18 and 45 years and with a body mass index (BMI) greater than 25 kg/m 2 . Following screening and baseline testing, women will be randomised by simple randomisation procedure using computer generated sequence allocation to undergo one of two 12-week supervised interventions: either HIIT or moderate intensity exercise (standard supervised exercise), or to standard care [Con] (unsupervised lifestyle advice) at a 1:1:1 allocation ratio. The primary outcome for this trial is to measure the improvements in metabolic health; specifically changes in insulin sensitivity in response to different exercise intensities. Baseline and post-intervention testing include anthropometric measurements, cardiorespiratory fitness testing, reproductive hormone profiles (anti-müllerian hormone and steroid profiles), metabolic health, health-related quality of life and mental health questionnaires and objective and subjective lifestyle monitoring. Reporting of the study will follow the CONSORT statement.; Discussion: This trial aims to demonstrate the comparative efficacy and maintenance of different exercise intensities to advance the understanding of PCOS management and provide insight into the optimal exercise intensity for improved cardiometabolic outcomes. Secondary outcomes will include the impact of different exercise protocols on reproductive hormone profiles, mental health and health-related quality of life.; Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12615000242527 . Registered on 17 March 2015.

Hiba, M., et al. (2021). "Systematic Review and Meta-Analysis of the efficacy and safety of Tramadol in pain management during outpatient hysteroscopy."
	
Hicks, L. E. and S. Yeo (2023). "Longitudinal Changes of Depressive Symptoms in Sedentary Women Who Exercised During Pregnancy." Women's health reports (New Rochelle, N.Y.) 4(1): 523-530.
	INTRODUCTION: Prenatal depression is a common disorder; however, little is known about how depressive symptoms manifest during pregnancy, including when symptoms present and what symptoms are common. This study aimed to better understand prenatal depressive symptoms during pregnancy in the postpartum period, as well as how exercise, such as walking and stretching, can improve depressive symptoms during pregnancy and the postpartum period. METHODS: A total of 55 women were assessed using the Beck Depression Inventory-II for depressive symptoms at 16 weeks, 28 weeks, and 2 months postpartum. Sedentary pregnant women at-risk for preeclampsia were randomly assigned to either a stretching or walking group for 40 minutes five times a week from 18 weeks of gestation until birth. The primary analyses were analysis of variance and mixed-effects models. RESULTS: All depressive symptoms decreased throughout pregnancy during the postpartum period, although this trend was not statistically significant. Cognitive-affective and somatic depressive symptoms had different trajectories during pregnancy into the postpartum period, but no significant difference was found. Statistically significant improvements were observed in loss of energy and change in sleeping pattern for the walking and stretching groups. CONCLUSION: The finding that physical activity improves the depressive symptoms' loss of energy and changes in sleeping patterns during pregnancy aligns with the existing literature, but little research has examined how individual depressive symptoms change throughout pregnancy into the postpartum period. Gaining a better understanding of the trajectories and manifestations of depressive symptoms during pregnancy and the postpartum period is essential for improving detection and treatment practices. Understanding when and how depressive symptoms are present is critical for the clinical diagnosis of this disorder.

Hidalgo-Padilla, L., et al. (2023). "Association between maternity leave policies and postpartum depression: a systematic review." Archives of Women's Mental Health 26(5): 571-580.
	PURPOSE: Working mothers are at greater risk for postpartum depression. Maternity leave characteristics, including length, wage replacement and employment protection, could have relevant implications for mothers' mental health. We propose to explore whether there is an association between maternity leave characteristics and postpartum depression. METHODS: We conducted a systematic review searching for randomized controlled trials, quasi-experimental, cohort or cross-sectional studies on five databases using search terms including maternity and parental leave and depression, as well as references in relevant articles. We identified 500 articles and included 23 of those. We used the EPHPP Quality Assessment Tool for Quantitative Studies to assess the quality of the studies. RESULTS: Paid and longer maternity leaves tend to be associated with a reduction of postpartum depression symptoms in high-income countries. No studies explored the association between employment protection and postpartum depression. The quality of studies ranged from strong to weak, mostly influenced by study design. CONCLUSION: More restrictive maternity leave policies tend to be associated with higher rates of postpartum depression, although more research needs to be conducted in the Global South.

Hidayat Yudi, M., et al. (2021). "Analysis of Curcumin as a Radiosensitizer in Cancer Therapy with Serum Survivin Examination: Randomised Control Trial." Asian Pacific journal of cancer prevention : APJCP 22(1): 139-143.
	Objective: One of the important treatments for cervical cancer is radiation therapy. This study sought to determine the role of curcumin as a radio-sensitizing agent for use with radiation therapy for cervical cancer. To accomplish this, we assessed the levels of survivin, which is an anti-apoptotic protein that plays a role in cell division and apoptosis inhibition.; Method: This study used a quasi-experimental design, including a pretest-posttest control group design approach. The study subjects included cervical carcinoma stage IIB-IIIB patients who were scheduled to undergo surgery at the Hasan Sadikin Hospital Bandung during the research period. The advanced cervical cancer patients were assigned to two groups: i) those who received curcumin + radiation therapy and ii) those who received placebo + radiation therapy.; Results: In the group treated with curcumin + radiation, 15 (75%) patients showed decreased survivin levels and 5 (25%) showed increased survivin levels. Whereas, in the placebo + radiation group, there were 8 (40%) patients who showed decreased survivin levels and 12 (60%) who showed increased survivin levels.; Conclusion: In conclusion, curcumin is an effective, alternative radiosensitizer agent for application in cervical cancer treatment.<br />.

Hill, A. M., et al. (2022). "Chlorhexidine Versus Iodine for Vaginal Preparation Before Hysterectomy: A Randomized Clinical Trial." Female Pelvic Medicine and Reconstructive Surgery 28(2): 77-84.
	Objective: The American College of Obstetricians and Gynecologists does not provide a recommendation regarding the preferred vaginal preparation solution. We intended to compare the effectiveness of chlorhexidine versus iodine in decreasing vaginal bacterial counts. Method(s): In this institutional review board-approved study, participants undergoing total hysterectomy via vaginal or laparoscopic approach were randomized to 4% chlorhexidine or 10% iodine for presurgical vaginal preparation. Swabs were collected from the vaginal mucosa before, then 30, 60, and 90 minutes after preparation. Our primary outcome was the number of positive cultures (>=5,000 bacteria) at 90 minutes. The secondary outcomes included the presence of selected pathogens, postoperative complications, and infections. The sample size of 71 per arm was calculated using P = 0.05, 80% power, and anticipating a 22% difference in positive cultures. Result(s): Between May 2018 and August 2019, 85 participants were randomized. The average age was 59.8 years (SD, 11.4), and the median Charlson Comorbidity Index score was 2 (minimum, 0; maximum, 6). Baseline bacterial counts were similar in both groups. Chlorhexidine demonstrated a lower percentage of positive cultures at 90 minutes (47.6% vs 85.4%; odds ratio, 10.6; P = 0.001). In addition, the median bacterial count in the chlorhexidine group was significantly lower than the iodine group (3,000 vs 24,000 colony-forming units, P < 0.001) at 90 minutes. No surgical site infections were identified in either group during the 30-day postoperative period, and there were no reported adverse reactions to either solution. Conclusion(s): Chlorhexidine resulted in substantially lower bacterial counts after preparation compared with iodine. Gynecologic surgeons may consider switching to 4% chlorhexidine for vaginal preparation before hysterectomy.Copyright © 2021 American Urogynecologic Society. All rights reserved.

Hillemanns, P., et al. (2023). "Innovative surgical concepts for cervical cancer." Onkologie 29(11): 956-966.
	Background: Three main topics have dominated the surgical treatment of early cervical cancer in recent years. The trend towards minimally invasive surgery has suffered a severe setback with the publication of the LACC trial (Laparoscopic Approach to Cervical Cancer, 2018). Reduced surgical radicalism with sentinel diagnostics and avoidance of radical hysterectomy are the two other topics. Material(s) and Method(s): Selective literature research, evaluation of own patient collectives and current congress reports are presented. Result(s): Abdominal radical hysterectomy became the standard procedure for the surgical treatment of early cervical cancer. This was followed by a plethora of secondary analyses ranging from registry-based data, proprietary data, to multicenter retrospective studies to identify the causes of laparoscopy's poor performance. However, only the initiated prospective randomized trials will give us the answer. Another trend is the avoidance of complete lymphadenectomy by sentinel diagnostics in early cervical cancer up to 4cm, which are mainly based on indocyanine green. Fortunately, this question will be answered with the SENTICOL-III study. Even with the introduction of trachelectomy for cervical carcinoma up to 2cm, we know that this stage has a very good prognosis. However, this FIGO (Federation Internationale de Gynecologie et d'Obstetrique) stage in the laparoscopic arm of the LACC study also had a significantly worse recurrence-free survival-although not significant due to the small number of cases. With the presentation of the SHAPE study comparing simple and radical hysterectomy at the American Society of Clinical Oncology (ASCO) 2023 congress, a further chapter on the reduction of surgical radicalism was opened.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Hilton, J., et al. (2022). "BMS-986158, a Small Molecule Inhibitor of the Bromodomain and Extraterminal Domain Proteins, in Patients with Selected Advanced Solid Tumors: Results from a Phase 1/2a Trial." Cancers 14(17): 4079.
	This phase 1/2a, open-label study (NCT02419417) evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of BMS-986158, a selective bromodomain and extraterminal domain (BET) inhibitor. Dose escalation was performed with 3 BMS-986158 dosing schedules: A (5 days on, 2 days off; range, 0.75-4.5 mg), B (14 days on, 7 days off; 2.0-3.0 mg), and C (7 days on, 14 days off; 2.0-4.5 mg). Eighty-three patients were enrolled and received >=1 BMS-986158 dose. Diarrhea (43%) and thrombocytopenia (39%) were the most common treatment-related adverse events (TRAEs). A lower incidence of TRAEs was found with schedules A (72%) and C (72%) vs. B (100%). Stable disease was achieved in 12 (26.1%), 3 (37.5%), and 9 (31.0%) patients on schedules A, B, and C, respectively. Two patients on schedule A with a 4.5-mg starting dose (ovarian cancer, n = 1; nuclear protein in testis [NUT] carcinoma, n = 1) experienced a partial response. BMS-986158 demonstrated rapid-to-moderate absorption (median time to maximum observed plasma concentration, 1-4 h). As expected with an epigenetic modifier, expression changes in select BET-regulated genes occurred with BMS-986158 treatment. Schedule A dosing (5 days on, 2 days off) yielded tolerable safety, preliminary antitumor activity, and a dose-proportional PK profile.Copyright © 2022 by the authors.

Himiniuc Loredana Maria, M., et al. (2021). "Transradial Embolization, an Underused Type of Uterine Artery Embolization Approach: A Systematic Review." Medicina (Kaunas, Lithuania) 57(2).
	Background and Objectives: The most utilized approach for the embolization of uterine arteries is the transfemoral path. However, the transradial approach (TRA) has been gaining popularity among cardiologic interventions in the last years but only few studies have shown its applicability in uterine myoma treatment. The objective of this paper is to assess the feasibility, safety and efficacy of TRA when compared with the transbrachial, transulnar or transfemoral approach (TFA) for uterine arteries embolization (UAE). Materials and methods: A systematic review of the literature that analyzes the TRA for UAE it was carried out, in order to assess its safety and effectiveness. It was systematically searched the literature (Google Scholar, PubMed/MEDLINE, Cochrane Library and Embase) using the words ''uterine artery embolization''/''uterine embolization'' and ''transradial''/''radial''. All the relevant papers published until March 2020 were retrieved and analyzed. Results: Ten studies were considered eligible for this topic. TRA is a comparable method with TFA for uterine artery embolization. Conclusions: These studies allowed us to conclude that TRA is as safe and efficient as TFA. Its advantages include few complications, shorter hospitalization period, and rapid mobilization but a steeper learning curve has the disadvantage of a longer learning curve compared to TFA. Yet, these findings are built on few reports and more research is needed.; Competing Interests: The authors declare no conflict of interest.

Hinchcliff, E., et al. (2022). "State of the science: Contemporary front-line treatment of advanced ovarian cancer." Gynecologic Oncology 166(1): 18-24.
	
Hinchcliff Emily, M., et al. (2023). "Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer." Cancer.
	Background: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).; Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS).; Results: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms.; Conclusions: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described. (© 2023 American Cancer Society.)

Hintz Graeme, C., et al. (2019). "Sclerotherapy for rectal prolapse in children: A systematic review and meta-analysis." Journal of pediatric surgery 54(5): 1083-1088.
	Background: Sclerotherapy is a commonly utilized treatment for rectal prolapse in children. This study systematically evaluates the effectiveness and complications of various sclerosing agents in treating pediatric rectal prolapse.; Methods: After protocol registration (CRD-42018088980), multiple databases were searched. Studies describing injection sclerotherapy for treatment of pediatric rectal prolapse were included, with screening and data abstraction duplicated. The methodological quality of included papers was assessed using the Methodological Index for Non-Randomized Studies (MINORS) score.; Results: Nineteen studies were identified, published between 1970 and 2017. Most studies were single institution case series, with median "N" 57+/-88.9 and mean MINORS score of 0.51+/-0.17 (perfect score = 1). 1510 patients with a mean age of 4.5 years were accounted for: 36.2% female, most without comorbidities. Mean follow up length was 30 months. The most common sclerosing agent described was ethanol (45%), followed by phenol (33%). The mean number of treatments per patient was 1.1+/-0.34. The overall success rate after a single sclerotherapy treatment was 76.9%+/-8.8%. The overall complication rate was 14.4%+/-2%.; Conclusions: Injection sclerotherapy appears effective and low-risk in the treatment of pediatric rectal prolapse and should be considered before more invasive surgical options. The available evidence is of relatively poor quality, and prospective comparative investigations are warranted.; Level of Evidence: 3 (meta-analysis of level 3 studies). (Copyright © 2019. Published by Elsevier Inc.)

Hipólito-Reis, M., et al. (2022). "Impact of curcumin, quercetin, or resveratrol on the pathophysiology of endometriosis: A systematic review." Phytotherapy research : PTR 36(6): 2416-2433.
	Endometriosis, a gynecological disease that affects reproductive age women is difficultly controlled in the long term by currently available treatments, prompting patients to adopt self-controlled interventions including dietary changes. The aim of this review is to provide evidence of how curcumin, quercetin, and resveratrol can act as natural interventions to control endometriosis. The review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was carried out in PubMed, Scopus, and Web of Science to gather together all the articles that study the specific actions of curcumin, resveratrol, or quercetin in endometriosis pathophysiology. All types of study designs including experimental data were considered. Thirty articles, including a clinical trial, were included. For the assessment of the quality of the selected studies that globally have "good quality", the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and the SYRCLE ROB tool criteria were used. By acting on mechanisms of inflammation, oxidative stress, cell proliferation, invasion and adhesion, apoptosis, angiogenesis and glucose and lipid metabolism, curcumin, quercetin, and resveratrol showed to have beneficial effects, evidencing their potential application in the endometriosis treatment. However, future clinical studies are necessary to determine the real efficacy of these compounds in human endometriosis. (© 2022 John Wiley & Sons Ltd.)

Hirata, T., et al. (2020). "Clinical practice guidelines for the treatment of extragenital endometriosis in Japan, 2018." The Journal of Obstetrics and Gynaecology Research.
	The aim of this publication is to disseminate the clinical practice guidelines for the treatment of intestinal, bladder/ureteral, thoracic and umbilical endometriosis, already published in Japanese, to non-Japanese speakers. For developing the original Japanese guidelines, the clinical practice guideline committee was formed by the research team for extragenital endometriosis, which is part of the research program of intractable disease of the Japanese Ministry of Health, Labor and Welfare. The clinical practice guideline committee formulated eight clinical questions for the treatment of extragenital endometriosis, which were intestinal, bladder/ureteral, thoracic and umbilical endometriosis. The committee performed a systematic review of the literature to provide responses to clinical questions and developed clinical guidelines for extragenital endometriosis, according to the process proposed by the Medical Information Network Distribution Service. The recommendation level was determined using modified Delphi methods. The clinical practice guidelines were officially approved by the Japan Society of Obstetrics and Gynecology and the Japan Society of Endometriosis. This English version was translated from the Japanese version. (© 2020 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Hiroaki, Y., et al. (2023). "Multicenter phase II investigator initiated trial (STATICE TRIAL, NCCH1615, UMIN 000029506) ; A novel anti-HER2 therapy of trastuzumab deruxtecan in HER2-expressing uterine carcinosarcoma." Journal of Obstetrics and Gynaecology Research 49(1): 369.
	[Objective] Uterine carcinosarcoma (UCS) is an aggressive malignant tumor. Previous studies reported that human epidermal growth factor receptor 2 (HER2) expression was detected in 20-50% of UCS patients. Here, we conducted a phase 2, multi-center clinical trial to evaluate the efficacy of trastuzumab deruxtecan (T-DXd) by targeting HER2. [Methods] Between February 2018 and June 2020 at 7 institutions in Japan, we enrolled standard chemotherapy-refractory UCS patients with HER2-expression assessed by immunohistochemistry. T-DXd was administered every 3 weeks until progressive disease (PD) or intolerable toxic effects were confirmed. The primary end-point was overall response rate (ORR) inHER2 2+/3+(2+/3+) on central review, and the secondary endpoints were ORR in HER2 1 + (1+) or more, progression-free survival, overall survival and incidence of adverse events. The trial design was based on the Bayesian strategy. [Results] 34 patients were enrolled, 22 patients with 2+/3+ and 10 patients with 1+ were included in the efficacy analysis. The number of complete response and partial response (PR) was 12 (55%), stable disease (SD) was 10 (45%) and no PD in 2+/3+, therefore, it exceeded the minimum required number of responders (4 out of 22 patients). In 1+ patients, the number of PR was 7 (70%), SD was 3 (30%) and no PD. Pneumonitis or interstitial lung disease with grade 1 to 3 occurred in 9 patients (27%) and no grade 4/5 events were reported. [Conclusion] The primary endpoint of ORR in 2+/3+ patients was met. T-DXd has also shown a promising efficacy in 1+ patients.

Hirte, H., et al. (2022). "Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II-IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma: A Practice Guideline." Current oncology (Toronto, Ont.) 29(1): 231-242.
	Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II-IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma.; Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded.; Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II-IV optimally debulked women.; Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.

Hisano, M., et al. (2023). "Multicenter, 2-dose single-group controlled trial of tacrolimus for the severe infertility patients." Medicine 102(32): e34317.
	Introduction: Infertility is estimated to affect 8% to 12% of reproductive-aged couples worldwide. While approximately 85% of infertile couples have an identified cause, the remaining 15% suffer physically and emotionally from unexplained intractable infertility. In recent years, maternal-to-fetal immunological abnormalities have attracted attention as mechanisms that differ from the conventional factors contributing to infertility and pregnancy loss. A T-helper 2 (Th2)-dominant immune state has been proposed as a maternal immune alteration to eliminate rejection and induce tolerance to a semi-allogeneic fetus. An imbalance in Th1 responses would not induce adequate maternal immune tolerance to the fetus or early embryos. Tacrolimus, widely used as an immunosuppressant agent in solid organ transplant recipients, is expected to suppress maternal rejection and promote tolerance to early embryos after assisted reproductive technology by modulating the immunological environment of the preimplantation endometrium. We planned an exploratory clinical trial to determine the efficacy, safety, and dosage of tacrolimus in women with intractable infertility.; Methods and Analysis: This is a multicenter, 2-dose, single-group controlled trial in infertile women who failed to achieve a chemical pregnancy despite multiple in vitro fertilization (IVF) and embryo transfer (ET) treatment cycles. The following 2 key selection criteria were set: no underlying factors of infertility despite appropriate evaluation and presence of Th1-dominant immune state, defined as a Th1/Th2 cell ratio ≥ 10.3 in the peripheral blood. A total of 26 eligible participants are randomly assigned (in a 2:1 ratio) to receive immunosuppressive therapy with oral tacrolimus at a daily dose of 2 mg or 4 mg. Tacrolimus is administered for 16 days starting from 2 days before ET. The primary endpoint is the presence of clinical pregnancy 3 weeks after IVF/ET treatment, and the secondary endpoint is the presence of biochemical pregnancy 2 weeks after IVF/ET treatment. Safety evaluation and biomarker discovery for tacrolimus treatment in infertile women will be conducted simultaneously.; Trial Registration Number: Japan Registry of Clinical Trials (jRCT; jRCTs031220235).; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hitova-Topkarova, D., et al. (2023). "Electronic brachytherapy for gynecological cancers - a systematic review." Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology 28(1): 79-87.
	Background: The purpose of this manuscript is to provide an in-depth literature review of the management of endometrial and cervical cancers with electronic brachytherapy.; Materials and Methods: An extensive literature search was performed and 9 articles were selected based on preset criteria.; Results: The reviewed studies provided dosimetric and clinical results. Patient populations were diverse and prescribed doses varied. When treatment plans were compared to those using cobalt 60 ( 60 Co) and iridium 192 ( 192 Ir) sources researchers found lower or equivalent doses in organs at risk while the doses at the applicator surface were significantly higher for electronic brachytherapy. In the eligible studies, a total of 72 patients received treatment with AxxentXoft vaginal applicator, 29 were treated with the Intrabeam vaginal applicator, and 8 with AxxentXoft cervical applicator.; Conclusions: All authors found that electronic brachytherapy was safe and well tolerated as higher mucosal doses did not present as adverse clinical effects. Electronic brachytherapy for gynecological cancers has the potential to achieve equivalent tumor control while minimizing bowel and urinary toxicity thus improving the quality of life. More clinical data is needed to stratify patients who would benefit the most.; Competing Interests: Conflict of interest None declared. (© 2023 Greater Poland Cancer Centre.)

Hlinecká, K., et al. (2022). "Uterus sparing surgery in adenomyosis and its impact on reproductive outcomes." Ceska gynekologie 87(4): 282-288.
	OBJECTIVE: The purpose of this study was to evaluate the appropriate surgical treatment of adenomyosis and its impact on reproductive outcomes. CONCLUSION: Patients with adenomyosis and fibroids may show a lower pregnancy rate and higher miscarriage rate than healthy individuals. However, there is no standard protocol for their optimal treatment, particularly in pregnancy-seeking or infertile women. Myomectomy is generally a commonly performed procedure that preserves fertility. On the other hand, the role of surgery in extensive uterine adenomyosis remains controversial, because adenomyosis often involves the whole uterus diffusely. It is almost impossible to remove all pathological tissue from the surrounding myometrium. Therefore, this procedure is called debulking/cytoreductive surgery. However, adenomyomectomy has also become a more common type of surgical intervention in recent years.

Hoare Joseph, I., et al. (2022). "Carvedilol targets β-arrestins to rewire innate immunity and improve oncolytic adenoviral therapy." Communications biology 5(1): 106.
	Oncolytic viruses are being tested in clinical trials, including in women with ovarian cancer. We use a drug-repurposing approach to identify existing drugs that enhance the activity of oncolytic adenoviruses. This reveals that carvedilol, a β-arrestin-biased β-blocker, synergises with both wild-type adenovirus and the E1A-CR2-deleted oncolytic adenovirus, dl922-947. Synergy is not due to β-adrenergic blockade but is dependent on β-arrestins and is reversed by β-arrestin CRISPR gene editing. Co-treatment with dl922-947 and carvedilol causes increased viral DNA replication, greater viral protein expression and higher titres of infectious viral particles. Carvedilol also enhances viral efficacy in orthotopic, intraperitoneal murine models, achieving more rapid tumour clearance than virus alone. Increased anti-cancer activity is associated with an intratumoural inflammatory cell infiltrate and systemic cytokine release. In summary, carvedilol augments the activity of oncolytic adenoviruses via β-arrestins to re-wire cytokine networks and innate immunity and could therefore improve oncolytic viruses for cancer patient treatment. (© 2022. The Author(s).)

Hodgetts, M., et al. (2022). "Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial." Lancet (London, England) 400(10361): 1426-1436.
	Background: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage.; Methods: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349.; Findings: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]).; Interpretation: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes.; Funding: National Institute of Health Research Health Technology Assessment Programme.; Competing Interests: Declaration of interests VHM is a National Institute for Health and Care Research (NIHR) clinical lecturer and has received an honorarium from Hologic. JD reports membership of the NIHR Clinical Trials Unit Standing Advisory Committee (May 1, 2016, to Sept 30, 2023). JEN is a member of the Health Technology Assessment (HTA) Maternal, Neonatal and Child Health Panel; receives funding from NIHR Efficacy and Mechanism Evaluation programme; participates in a Data Monitoring and Ethics Committee for GlaxoSmithKline; and is a paid consultant for DILAFOR. RKM receives funding from NIHR HTA and programme grants for Applied Health Research schemes; is a steering committee member of the Saving Babies Lives Care Bundle; and a paid Clinical Advisory Board member for Surepulse (a company designing neonatal monitors). All other authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Hodgetts-Morton, V., et al. (2021). "C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth-study protocol for a randomised controlled trial." Trials 22(1): 529.
	Background: Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach.; Methods: C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0-27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children's Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat.; Discussion: To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies.; Trial Registration: ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018. (© 2021. The Author(s).)

Hoe, V., et al. (2021). "Urethral bulking agents for the treatment of stress urinary incontinence in women: A systematic review." Neurourology and Urodynamics 40(6): 1349-1388.
	Aims: To perform a systematic review to assess and compare the efficacy and safety of all urethral bulking agents (UBAs) available for the treatment of stress urinary incontinence (SUI) in women. Method(s): This systematic review was conducted in accordance with the PRISMA guideline. A systematic search was conducted using the Ovid Medline, Embase and PubMed databases. Studies were included if they involved women who underwent either Bulkamid, Macroplastique, Durasphere, Coaptite, or Urolastic injections for the treatment of SUI. A total of 583 articles were screened with 56 articles included. A qualitative analysis was performed. Result(s): The newer synthetic UBAs are not inferior to Contigen, with variable mean success rates of 30%-80% in the short-term. Better long-term success rates were found with Bulkamid (42%-70%), Coaptite (60%-75%), and Macroplastique (21%-80%) on qualitative review. Urinary tract infection rates were similar between bulking agents (4%-10.6%) although temporary acute urinary retention was more commonly associated with Coaptite (mean: 34.2%), and de novo urgency in Durasphere (mean: 24.7%). Significant complications such as migration into lymph nodes was reported with Durasphere. Erosion was reported with Macroplastique, Coaptite, and Urolastic, with a rate as high as 24.6% in one study of Urolastic. Conclusion(s): Available data support the use of Bulkamid and Macroplastique, which has shown a short-term efficacy of 30%-90% and 40%-85% respectively, and long-term efficacy of 42%-70%, and 21%-80%, respectively. Bulkamid appears to have a more favorable safety profile, with no cases of erosion or migration of product associated with its use. Direct comparisons of UBAs have not been performed.Copyright © 2021 Wiley Periodicals LLC

Hoegl, J., et al. (2022). "Peritoneal carcinomatosis after minimally invasive surgery versus open radical hysterectomy: systematic review and meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(12): 1497-1504.
	Objective: To assess the incidence of peritoneal carcinomatosis in patients undergoing minimally invasive or open radical hysterectomy for cervical cancer.; Methods: The MEDLINE (accessed through Ovid), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Clinical Trials, and Scopus databases were searched for articles published from inception up to April 2022. Articles published in English were considered. The included studies reported on patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IIA squamous cell carcinoma, adenocarcinoma, and/or adenosquamous carcinoma of the cervix who underwent primary surgery. Studies had to report at least one case of peritoneal carcinomatosis as a recurrence pattern, and only studies comparing recurrence after minimally invasive surgery versus open surgery were considered. Variables of interest were manually extracted into a standardized electronic database. This study was registered in PROSPERO (CRD42022325068).; Results: The initial search identified 518 articles. After the removal of the duplicate entries from the initial search, two authors independently reviewed the titles and abstracts of the remaining 453 articles. Finally, 78 articles were selected for full-text evaluation; 22 articles (a total of 7626 patients) were included in the analysis-one randomized controlled trial and 21 observational retrospective studies. The most common histology was squamous cell carcinoma in 60.9%, and the tumor size was <4 cm in 92.8% of patients. Peritoneal carcinomatosis pattern represented 22.2% of recurrences in the minimally invasive surgery approach versus 8.8% in open surgery, accounting for 15.5% of all recurrences. The meta-analysis of observational studies revealed a statistically significant higher risk of peritoneal carcinomatosis after minimally invasive surgery (OR 1.90, 95% CI 1.32 to 2.74, p<0.05).; Conclusion: Minimally invasive surgery is associated with a statistically significant higher risk of peritoneal carcinomatosis after radical hysterectomy for cervical cancer compared with open surgery.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Hoek, A., et al. (2022). "Effects of preconception weight loss after lifestyle intervention on fertility outcomes and pregnancy complications." Fertility and Sterility 118(3): 456-462.
	It is well documented that obesity decreases natural fertility among men and women as well as pregnancy chances after conventional infertility and assisted reproductive technology (ART)-based treatments. Moreover, pregnancy complications are increased in women with overweight and obesity. General guidelines on the treatment of obesity recommend lifestyle intervention, including diet and exercise as the first-line treatment, coupled with or without medical treatments, such as weight loss medication or bariatric surgery, to reduce complications of obesity in adults. In the context of infertility in various countries and infertility clinics, there is a body mass index limit for public refund of infertility treatment of women with obesity. In this respect, it is important to investigate the evidence of effects of lifestyle intervention preceding infertility treatment on reproductive outcomes. The combined results of 15 randomized controlled trials (RCTs) of the effectiveness of preconception lifestyle intervention on reproductive outcomes documented in the latest systemic review and meta-analysis, together with the most recent RCT performed in 2022 are discussed. The current evidence suggests that greater weight loss and increase in clinical pregnancy, live birth, and natural conception rates after lifestyle intervention compared with no intervention were observed, but it seems no beneficial effect of lifestyle intervention preceding ART was observed on these parameters. With respect to potential harm of lifestyle intervention, there is no significant increased risk of early pregnancy loss, although the most recent RCT (not included in the systematic review and meta-analysis) showed a trend toward an increased risk. Complications during pregnancy, such as early pregnancy loss and maternal as well as fetal and neonatal complications, are underreported in most studies and need further analysis in an individual participant data meta-analysis. Limitations of the studies as well as future perspectives and challenges in this field of research will be highlighted. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Hofmann, K., et al. (2023). "Combinatory Effects of Training and Nutritive Administration of Carbohydrates and Protein via Food on Strength in Postmenopausal Women, and Old Men and Women." Nutrients 15(6).
	The age-related loss of muscle mass promotes many impairments. Training and protein supplementation are suggested to prevent muscle wasting, but recommendations for all populations are not based on scientific evidence. This study combines protein/carbohydrate supplementation (PCS) and training for seniors and postmenopausal women. Project A: 51 postmenopausal women (PMW, 57.3 ± 3.0 years old) underwent health-oriented training (12 weeks, moderate-strength training + moderate-endurance training). The intervention group (IG) additionally received 110 g sour milk cheese (SMC) and toast. Project B: 25 women and 6 men (65.9 ± 4.9 years old) performed intense sling training (12 weeks). The IG additionally received 110 g SMC, toast, and buttermilk. Strength was tested before and after in both studies. Project A: there was significant increase in strength, no additional effect of PCS, and a reduction in body fat in the controls. Project B: there was significant increase in strength, significant additional effects of PCS for trunk strength, and a significant reduction in body weight. Combining training and PCS may counteract strength loss. Combined endurance/resistance training is recommended to PMW for whom the benefits of PCS are restricted. Aged subjects may benefit from PCS when training intensely, but these benefits may be strongly individual.

Hogwood Austin, C., et al. (2023). "The acute effects of exercise intensity and inorganic nitrate supplementation on vascular health in females after menopause." Journal of applied physiology (Bethesda, Md. : 1985) 135(5): 1070-1081.
	Menopause is associated with reduced nitric oxide bioavailability and vascular function. Although exercise is known to improve vascular function, this is blunted in estrogen-deficient females post-menopause (PM). Here, we examined the effects of acute exercise at differing intensities with and without inorganic nitrate (NO 3 - ) supplementation on vascular function in females PM. Participants were tested in a double-blinded, block-randomized design, consuming ∼13 mmol NO 3 - in the form of beetroot juice (BRJ; n = 12) or placebo (PL; n = 12) for 2 days before experimental visits and 2 h before testing. Visits consisted of vascular health measures before ( time point 0 ) and every 30 min after ( time points 60, 90, 120, 150 , and 180 ) calorically matched high-intensity exercise (HIE), moderate-intensity exercise (MIE), and a nonexercise control (CON). Blood was sampled at rest and 5-min postexercise for NO 3 - , NO 2 - , and ET-1. BRJ increased N-oxides and decreased ET-1 compared with PL, findings which were unchanged after experimental conditions ( P < 0.05). BRJ improved peak Δflow-mediated dilation (FMD) compared with PL ( P < 0.05), defined as the largest ΔFMD for each individual participant across all time points. FMD across time revealed an improvement ( P = 0.05) in FMD between BRJ + HIE versus BRJ + CON, while BRJ + MIE had medium effects compared with BRJ + CON. In conclusion, NO 3 - supplementation combined with HIE improved FMD in postmenopausal females. NO 3 - supplementation combined with MIE may offer an alternative to those unwilling to perform HIE. Future studies should test whether long-term exercise training at high intensities with NO 3 - supplementation can enhance vascular health in females PM. NEW & NOTEWORTHY This study compared exercise-induced changes in flow-mediated dilation after acute moderate- and high-intensity exercise in females postmenopause supplementing either inorganic nitrate (beetroot juice) or placebo. BRJ improved peak ΔFMD postexercise, and BRJ + HIE increased FMD measured as FMD over time. Neither PL + MIE nor PL + HIE improved FMD. These findings suggest that inorganic nitrate supplementation combined with high-intensity exercise may benefit vascular health in females PM.

Hoke, T. P., et al. (2019). "Evidence-based review of vaginal native tissue hysteropexy for uterovaginal prolapse." Obstetrical and Gynecological Survey 74(7): 429-435.
	Importance As surgical techniques evolve in the treatment of pelvic organ prolapse and patient preferences are better understood, more studies are investigating uterine-sparing procedures for efficacy, safety, and potentially improved quality of life. Much of the literature reflects the use of mesh material in uterine-sparing procedures, and there is a paucity of data regarding the safety and efficacy of native tissue uterine-sparing procedures for the treatment of pelvic organ prolapse. Objective To summarize existing evidence regarding objective and subjective outcomes of uterine-preserving procedures including the Manchester procedure (MP) as well as native tissue uterovaginal hysteropexy with repairs, namely, uterosacral hysteropexy (USH) and sacrospinous hysteropexy (SSH), compared with outcomes of total vaginal hysterectomy (TVH) with repairs for the management of uterovaginal prolapse. Evidence Acquisition A review of the literature included MEDLINE, Cochrane, and clinicaltrials.gov databases. Results Few level 1 data exist comparing outcomes of native tissue hysteropexy to vaginal hysterectomy for management of uterovaginal prolapse. In general, outcomes of the MP for the management of uterovaginal prolapse revealed that compared with TVH it is associated with shorter operative times, lower estimated blood loss and risk of blood transfusion with no difference in hospital stay, and similar quality of life and sexual function outcomes. Retrospective data suggest no difference with respect to recurrent prolapse of any compartment between USH and TVH with repairs. Level 1 data reveal that SSH has been shown to have similar 1-year outcomes and safety compared with TVH with native tissue suspension. Women with stage 4 prolapse who undergo an SSH may be at higher risk of recurrence and may benefit from an alternative method of apical prolapse repair. Conclusions and Relevance More level 1 data are needed in order to robustly understand long-term differences in outcomes between native tissue uterine-conserving versus vaginal hysterectomy surgical approaches in women with uterovaginal prolapse. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to explain why uterine-sparing procedures for uterovaginal prolapse are becoming more popular in the United States; compare similarities and differences in subjective and objective outcomes between the MP and TVH; describe subjective and objective outcomes between vaginal native tissue USH and SSH to TVH; and analyze if uterine-sparing surgical procedures impact pregnancy outcomes.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Hollebecque, A., et al. (2021). "Safety and Antitumor Activity of α-PD-L1 Antibody as Monotherapy or in Combination with α-TIM-3 Antibody in Patients with Microsatellite Instability-High/Mismatch Repair-Deficient Tumors." Clinical cancer research : an official journal of the American Association for Cancer Research 27(23): 6393-6404.
	PURPOSE: Immune checkpoint inhibitors show high response rates and durable clinical benefit in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumors. However, 50%-60% do not respond to single-agent anti-programmed death-1/programmed death ligand 1 (PD-1/PD-L1) antibodies, and approximately 50% of responders relapse within 6-12 months. This phase Ib trial evaluated safety and antitumor activity of anti-PD-L1 antibody LY3300054 monotherapy or in combination with anti-TIM-3 antibody LY3321367 in patients with MSI-H/dMMR advanced solid tumors. PATIENTS AND METHODS: Eligible patients ≥18 years without prior anti-PD-1/PD-L1 therapy received LY3300054 monotherapy (N = 40) or combination (N = 20); patients with PD-1/PD-L1 inhibitor-resistant/refractory tumors received the combination (N = 22). LY3300054 (700 mg) and anti-TIM-3 antibody (cycles 1-2: 1,200 mg, cycle 3 onward: 600 mg) were administered intravenously every 2 weeks. Primary endpoints were safety and tolerability. RESULTS: Eighty-two patients were enrolled. Most had colorectal (n = 39, 47.6%) or endometrial (n = 14, 17.1%) tumors. More than 70% of patients in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort had received ≥3 treatment lines. Treatment-related adverse events (TRAE) occurred in 22 patients (55.0%) receiving monotherapy, 13 (65.0%) in the PD-1/PD-L1 inhibitor-naïve combination cohort, and 6 (27.3%) in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort. A total of 2 patients (5.0%) receiving monotherapy and 3 (7.1%) receiving the combination experienced grade ≥3 TRAEs. Objective responses occurred in 13 patients (32.5%) with monotherapy, 9 (45.0%) in the PD-1/PD-L1 inhibitor-naïve combination cohort, and 1 patient (4.5%) in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort. CONCLUSIONS: LY3300054 monotherapy and combined LY3300054/anti-TIM-3 had manageable safety profiles. Both regimens showed promising clinical activity against PD-1/PD-L1 inhibitor-naïve MSI-H/dMMR tumors. The combination had limited clinical benefit in patients with PD-1/PD-L1 inhibitor-resistant/refractory MSI-H/dMMR tumors.

Holloway Robert, W., et al. (2023). "Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial." JAMA Oncology 9(7): 903-908.
	Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need.; Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC.; Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022.; Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab.; Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS).; Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths.; Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial.; Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

Holt-Kentwell, A., et al. (2022). "Evaluating interventions and adjuncts to optimize pregnancy outcomes in subfertile women: an overview review." Human Reproduction Update 28(4): 583-600.
	Background: There is a wealth of information regarding interventions for treating subfertility. The majority of studies exploring interventions for improving conception rates also report on pregnancy outcomes. However, there is no efficient way for clinicians, researchers, funding organizations, decision-making bodies or women themselves to easily access and review the evidence for the effect of adjuvant therapies on key pregnancy outcomes in subfertile women.; Objective and Rationale: The aim was to summarize all published systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions in the subfertile population, specifically reporting on the pregnancy outcomes of miscarriage and live birth. Furthermore, we aimed to highlight promising interventions and areas that need high-quality evidence.; Search Methods: We searched the Cochrane Database of Systematic Reviews and PubMed clinical queries SR filter (inception until July 2021) with a list of key words to capture all SRs specifying or reporting any miscarriage outcome. Studies were included if they were SRs of RCTs. The population was subfertile women (pregnant or trying to conceive) and any intervention (versus placebo or no treatment) was included. We adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for determining the quality of the evidence. Exclusion criteria were overview reviews, reviews that exclusively reported on women conceiving via natural conception, reviews including non-randomized study designs or reviews where miscarriage or live birth outcomes were not specified or reported.; Outcomes: The primary outcome was miscarriage, defined as pregnancy loss <24 weeks of gestation. Data were also extracted for live birth where available. We included 75 published SRs containing 121 251 participants. There were 14 classes of intervention identified: luteal phase, immunotherapy, anticoagulants, hCG, micronutrients, lifestyle, endocrine, surgical, pre-implantation genetic testing for aneuploidies (PGT-As), laboratory techniques, endometrial injury, ART protocols, other adjuncts/techniques in the ART process and complementary interventions. The interventions with at least moderate-quality evidence of benefit in reducing risk of miscarriage or improving the chance of a live birth are: intrauterine hCG at time of cleavage stage embryo transfer, but not blastocyst transfer, antioxidant therapy in males, dehydroepiandrosterone in women and embryo medium containing high hyaluronic acid. Interventions showing potential increased risk of miscarriage or reduced live birth rate are: embryo culture supernatant injection before embryo transfer in frozen cycles and PGT-A with the use of fluorescence in situ hybridization.; Wider Implications: This review provides an overview of key pregnancy outcomes from published SRs of RCTs in subfertile women. It provides access to concisely summarized information and will help clinicians and policy makers identify knowledge gaps in the field, whilst covering a broad range of topics, to help improve pregnancy outcomes for subfertile couples. Further research is required into the following promising interventions: the dose of progesterone for luteal phase support, peripheral blood mononuclear cells for women with recurrent implantation failure, glucocorticoids in women undergoing IVF, low-molecular-weight heparin for unexplained subfertility, intrauterine hCG at the time of cleavage stage embryo or blastocyst transfer and low oxygen concentrations in embryo culture. In addition, there is a need for high-quality, well-designed RCTs in the field of reproductive surgery. Finally, further research is needed to demonstrate the integrated effects of non-pharmacological lifestyle interventions. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Holtzman, S., et al. (2023). "Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy." Gynecologic Oncology 174: 273-277.
	Objective: The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/- para-aortic lymphadenectomy (LND).; Methods: Patients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC).; Results: Out of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3-84.0%) in the SLN group and 71.3% (95% CI 62.0-78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56-2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47-2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1-93.7%) in the SLN group and 95.1% (95% CI 89.4-97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39-10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94-8.95, p = 0.06).; Conclusions: There was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hong David, S., et al. (2023). "Autologous T cell therapy for MAGE-A4 + solid cancers in HLA-A*02 + patients: a phase 1 trial." Nature medicine 29(1): 104-114.
	Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies. (© 2023. The Author(s).)

Hong, X., et al. (2024). "Combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer: a real-world cohort study and meta-analysis." Therapeutic advances in medical oncology 16: 17588359231221336.
	Background: Anlotinib is a novel oral small-molecule receptor tyrosine kinase inhibitor. However, the efficacy and safety of its combined use with chemotherapy remain unclear in patients with advanced ovarian cancer.; Objectives: To assess the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer.; Design: A multi-center retrospective real-world analysis and a meta-analysis.; Data Sources and Methods: We enrolled patients with advanced ovarian cancer who received a combination therapy of Anlotinib and chemotherapy from 15 medical centers. We also searched electronic databases for studies assessing the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with ovarian cancer. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS).; Results: A total of 71 patients, who were predominantly recurrent cases, were included in the real-world study. The ORR and DCR of the included patients were 40.8% and 76.1%, respectively; and their mPFS was 4.6 months. The log-rank test showed that previous antiangiogenic therapy was related to a longer mPFS (p < 0.05). Five studies in total were eligible for meta-analysis. The random-effects meta-analysis model showed that the ORR, DCR, and mPFS were 33.8% [95% confidence interval (CI) 22.7-44.8% from four studies], 90.6% (95% CI 73.6-99.9% from five studies), and 6.6 months (95% CI 4.9-8.4 months from five studies). The most common adverse events were hand-foot syndrome and hypertension.; Conclusion: The combined use of Anlotinib with chemotherapy showed potential in treating patients with advanced ovarian cancer, with a tolerable safety profile.; Competing Interests: The authors declare that there is no conflict of interest. (© The Author(s), 2024.)

Hong Yeon, H., et al. (2022). "Clinical efficacy of dual trigger with human chorionic gonadotropin and a gonadotropin-releasing hormone agonist for women undergoing fertility preservation." Reproductive Medicine and Biology 21(1): e12440.
	Purpose: To determine the optimal maturation method to increase the yield of mature oocytes, especially for cancer patients with fewer chances of fertility preservation (FP) before gonadotoxic therapy.; Methods: A total of 373 cycles in 293 patients undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol were enrolled. The control group ( n = 225) received 250 µg of recombinant human chorionic gonadotropin (rhCG) while the study group ( n = 148) received 250 µg of rhCG and 0.2 mg of triptorelin for triggering. Subgroup analyses were performed for stimulation cycles with diminished ovarian reserve (DOR; anti-Müllerian hormone (AMH) levels <1.1 ng/ml, n = 86), with endometrioma ( n = 104), or with breast cancer and endometrial cancer using 5 mg of letrozole during the COS cycles ( n = 84).; Results: There was no significant difference in the baseline characteristics or the number of total and mature oocytes between the two groups. Subgroup analyses for women with endometrioma or DOR showed similar results. However, the dual trigger group had a significantly higher number of mature oocytes than the rhCG trigger group in breast and endometrial cancer patients using letrozole during the COS cycles (6.9 ± 6.0 vs. 4.6 ± 3.6, p = 0.034). The maturation rate was higher in the dual trigger group, although the difference was not statistically significant (59.3 ± 26.7 vs. 50.0 ± 28.0, p = 0.124).; Conclusions: Dual triggering can be an efficient maturation method to maximize the yield of mature oocytes in breast or endometrial cancer patients using letrozole-combined GnRH antagonist protocol for FP.; Competing Interests: None. (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Hongyi, W. and M. Caihong (2022). "Outcomes of women treated with levonorgestrel-releasing intrauterine system for early endometrial cancer: a systematic review and meta-analysis."
	
Hongyu, Y., et al. (2022). "Acupuncture combined with metformin for polycystic ovary syndrome: a protocol for systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Hoogstad-van Evert, J. S., et al. (2020). "Harnessing natural killer cells for the treatment of ovarian cancer." Gynecologic Oncology 157(3): 810-816.
	Introduction: Adoptive cellular immunotherapy could be an interesting new treatment option for ovarian carcinoma (OC), as research has demonstrated that OC is an immunogenic disease. In particular, natural killer (NK) cells have attracted attention due to their ability to kill tumor cells without prior sensitization. The therapeutic value of allogeneic NK cells has been first observed in hematological cancers and is increasingly being explored in solid tumors. Method(s): To substantiate the rationale for NK cell therapy in OC we performed a literature search in the Pubmed database and in the international trial register clinicaltrials.gov with attention for the effect of OC on NK cell function, the effect of current treatment on NK cell biology and the evidence on the therapeutic value of NK cell therapy against OC. Result(s): In six clinical trials only 31 OC patients have been reported that received NK cell adoptive transfer. The majority of patients reached stable disease after NK cell therapy, with a mild pattern of side effects. In patients who received repeated infusions, more complete responses are described. All reported studies investigated the intravenous infusion of NK cells. Whereas the studies that are currently recruiting, investigate intraperitoneal infusion of allogeneic NK cells. Conclusion(s): In this review the pre-clinical evidence and current trials on NK cell immunotherapy in OC patients are summarized. Furthermore, challenges that have to be overcome for NK cell adoptive therapy to have a significant impact on disease outcome are discussed.Copyright © 2020 The Authors

Hooker Angelo, B., et al. (2022). "The link between intrauterine adhesions and impaired reproductive performance: a systematic review of the literature." BMC Pregnancy and Childbirth 22(1): 837.
	Background: Intrauterine adhesions (IUAs) are one of the main reproductive system diseases in women worldwide. Fusion between the injured opposing walls leads to partial-to-complete obliteration of the cavity and/or cervical canal. The main clinical manifestations in case of IUAs are menstrual disturbances, cyclic pain and reproductive disorders. The reproductive outcomes of women with IUAs remain limited and inefficient compared to women without IUAs, even after adhesiolysis. An exact understanding of the underlying mechanisms and processes to explain the compromised reproductive performance and outcomes in case of IUAs are lacking.; Methods: A systematic literature review of MEDLINE-PubMed (1966 to January 2022) and EMBASE (1974 to January 2022) was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they reported underlying causes, related mechanisms and processes to explain the association between IUAs and impaired reproductive performance, pregnancy and obstetric complications.; Results: After an extensive review of the literature, 58 articles were identified reporting underlying mechanisms to explain the association between IUAs and impaired fertility. Intrauterine scarring influences the process of fertilization, reproductive performance and ultimately reproductive outcome. IUAs can disturb the cervico-utero-tubal sperm transport and result in an avascular and unresponsive endometrium with decreased receptivity and thickness. Abnormal decidualization and abnormal trophoblastic infiltration leads to placental attachment disorders. Moreover, the risk for premature delivery, intrauterine fetal growth restriction and fetal anomalies is increased in case of IUAs.; Conclusion: The impact of IUAs on reproductive performance, even after adhesiolysis, is becoming more apparent. The postulated mechanisms to explain the association are related to sperm transport, embryo implantation and placentation. Prevention, by preserving the basal layer of the endometrium is essential. Effective and evidence-based strategies for the prevention of endometrial injury and formation of IUAs, are urgently needed. (© 2022. The Author(s).)

Hooker Angelo, B., et al. (2021). "Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial." Human reproduction (Oxford, England) 36(1): 70-81.
	Study Question: Are the long-term reproductive outcomes following recurrent dilatation and curettage (D&C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs.; Summary Answer: Reproductive outcomes in women with identified and treated IUAs following recurrent D&C for miscarriage are impaired compared to women without IUAs; fewer ongoing pregnancies and live births are achieved with a prolonged time to a live birth.; What Is Known Already: The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance.; Study Design, Size, Duration: This was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&C for miscarriage. All included women received a diagnostic hysteroscopy 8-12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization.; Participants/materials, Setting, Methods: Between December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&C, were randomized for D&C alone or D&C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Additionally, the medical files of all participants were reviewed. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded.; Main Results and the Role of Chance: In women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value <0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups.; Limitations, Reasons for Caution: In the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol; the influence of IUAs on reproductive outcome may therefore be underestimated. Women undergoing a recurrent D&C for miscarriage were included, a specific group likely to generate clinically significant adhesions. The findings should therefore not be generalized to all women undergoing D&C for miscarriage.; Wider Implications of the Findings: As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&C in women with a miscarriage. In case D&C is necessary, application of ACP gel should be considered.; Study Funding/competing Interest(s): The original PAPA study (NTR 3120) was an investigator initiated study that was funded by the Foundation for scientific investigation in Obstetrics and Gynaecology of the Saint Lucas Andreas Hospital (currently renamed OLVG Oost), SWOGA. The syringes containing ACP gel were received from Anika Therapeutics, the manufacturer of Hyalobarrier® Gel Endo. The current follow-up study was also an investigator-initiated study without funding. The funder and sponsor had no role in the design of this follow-up study, data collection, data analysis, data interpretation, trial design, patient recruitment, writing of the report or any aspect pertinent to the study. ABH, RAL, JAFH and JWRT have no conflict to declare. HAMB reports being a member of safety board research Womed.; Trial Registration Number: Netherlands Trial Register NTR 3120. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Hooker Angelo, B., et al. (2022). "Reproductive outcomes in women with mild intrauterine adhesions; a systematic review and meta-analysis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(25): 6933-6941.
	Background: Moderate to severe intrauterine adhesions (IUAs) may greatly impact fertility, predisposing to pregnancy and obstetric complications. The impact of mild IUAs on reproductive performance remains unclear. A systematic review and meta-analysis was performed to examine the long-term reproductive outcomes in women with hysteroscopic identified and treated mild IUAs mild intrauterine adhesions (IUAs).; Methods: An electronic literature search was conducted using MEDLINE and EMBASE from inception to June 2019. All prospective cohort, cross-sectional studies or randomized controlled trials Clinical trials in which reproductive outcomes of women with mild IUAs, were reported were included.; Results: Five studies, reporting on reproductive outcomes of 229 women with hysteroscopic identified and treated mild IUAs, were included. The pregnancy rate was 62.3% (142 of 228; 95% CI: 0.55-0.72, I 2 25%, p = .21) and in 86.6% (123 of 142) a live birth was encountered (95% CI: 0.71-0.97) with 83.1% (108 out of 130) term deliveries (95% CI: 0.53-0.95). A miscarriage was reported in 10% (13 of 130; 95% CI: 0.02-0.26). Due to the lack of a control group, reproductive outcomes were compared to a general population. Pregnancy and live birth rates were significantly lower in women with identified and treated mild IUAs, 90% versus 62.3% and respectively 99.5% versus 86.6%. The miscarriage rate was similar. Data on obstetric and neonatal outcomes are lacking.; Conclusions: Women with hysteroscopic identified and treated mild IUAs seem to have lower pregnancy and live birth rate compared to the general population. Future studies consisting of a large cohort of women with hysteroscopic identified and treated IUAs with structural follow-up and a control group are needed to confirm our findings.

Hoover, S. E., et al. (2021). "Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS." The Journal of Clinical Endocrinology and Metabolism 106(5): e2151-e2161.
	CONTEXT: Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin. OBJECTIVE: To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness. METHODS: Secondary analysis of a randomized crossover trial. PARTICIPANTS: Thirty women diagnosed with PCOS. INTERVENTION: Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores. RESULTS: After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase. CONCLUSION: These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.

Hope Medicine, C. and Ltd (2021). A Study to Assess the Efficacy and Safety of HMI-115 in Subjects With Endometriosis-Associated Pain.
	No Results Available Drug: HMI-115|Drug: Placebo Change of dysmenorrhea (DYS) measured by Numeric Rating Scale (NRS) from Baseline to Week 12|Change in DYS measured by NRS from Baseline to Week 24|Change of non-menstrual pelvic pain (NMPP) measured by NRS from Baseline to Week 12 and 24|Change in dyspareunia (DYSP) measured by NRS from Baseline to Week 12 and 24|Change from Baseline (CFB) in the monthly mean Endometriosis Daily Impact Pain Scale for DYS, NMPP and DYSP|CFB by visit in permitted rescue medication use|Change in menstrual period heaviness (bleeding) from Baseline by visit Female Phase 2 152 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment HMI-115EM201 April 2025

Hori, K., et al. (2021). "A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial." Journal of Gynecologic Oncology 32(4): e64.
	OBJECTIVE: To determine the safety and efficacy of dose-dense (dd) paclitaxel (PTX) and carboplatin (CBDCA) in treating advanced or recurrent endometrial cancer. METHODS: Women aged 20-75 years with histologically confirmed endometrial cancer, the International Federation of Gynecology and Obstetrics (FIGO) stage III disease with some residual tumor, FIGO stage IV disease, recurrence after front-line curative treatment, or recurrence after second-line chemotherapy or radiotherapy were enrolled in this study. PTX (80 mg/m²) was administered intravenously (IV) to every participant on days 1, 8, and 15, and CBDCA (area under the curve of 5) was administered IV on day 1 once every 3 weeks until the disease progressed, unacceptable adverse events occurred, or consent was withdrawn. The primary endpoint was the response rate (RR), while the secondary endpoints were progression-free survival, overall survival, and adverse effects. RESULTS: Forty-eight participants were enrolled, and 46 were eligible to receive treatment. The patients' median age was 61 years (range, 43-76 years). Twenty-two participants had experienced recurrence, and the remaining patients had primary advanced endometrial cancer. There were 10 cases of serous carcinoma, 3 cases of endometrioid carcinoma G3, 2 cases of carcinosarcoma, and 2 cases of clear-cell carcinoma according to histology. Twenty-nine participants (63.0%) received ≥6 cycles of chemotherapy. The RR (complete, 13 cases; partial, 20 cases) was 71.3% (95% confidence interval: 59.0%-84.5%). CONCLUSION: The dd PTX with CBDCA is feasible and available as a treatment option for advanced or recurrent endometrial cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN000017138.

Horne, A. W., et al. (2020). "Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial." Lancet 396: 909–917.
	
Horowitz, E., et al. (2021). "A randomized controlled trial of vaginal progesterone for luteal phase support in modified natural cycle - frozen embryo transfer." Gynecological Endocrinology 37(9): 792‐797.
	Objective: Our aim was to study whether luteal phase support (LPS) increases the live‐birth rate (LBR) in women undergoing modified natural cycle (mNC) frozen‐thawed embryo transfer (FET). Methods: In a randomized controlled trial, conducted at a university‐affiliated tertiary medical center, a total of 59 patients aged 18–45 years, underwent mNC‐FET. FET was performed in mNC following ovulation triggering by hCG. Patients were randomized into two groups; The No‐LPS Group included 28 women who did not receive LPS, and the LPS Group included 31 women who received vaginal progesterone for LPS. The main outcome measure was LBR. Results: Baseline demographic and clinical characteristics were comparable between the study groups. The no‐LPS group and the LPS group did not differ with regard to clinical pregnancy rate (21.4% vs. 32.3%; respectively, p =.35), LBR (17.9% vs. 19.4%; respectively, p =.88), or spontaneous miscarriage rate (3.6% vs. 12.9%; respectively, p =.35). On multivariate logistic regression analysis, LPS was not associated with LBR after controlling for confounders. Conclusion: The results of our study suggest that LPS after mNC‐FET does not improve the reproductive outcome, and therefore, might not be necessary.Clinicaltrials.gov identifier: NCT01483365.

Horowitz, E. and A. Weissman (2020). "The stair-step approach in treatment of anovulatory PCOS patients." Therapeutic advances in reproductive health 14: 2633494120908818.
	Clomiphene citrate (CC) is a widely accepted first-line treatment for anovulatory patients with polycystic ovarian syndrome (PCOS). The current practice is to prescribe CC with gradual dose increments until ovulation is achieved. Typically, progesterone withdrawal bleeding is induced between each dose increment and before the commencement of gonadotropin therapy in CC-resistant patients. It has been recently suggested that dose increments of CC can be administered once failure to induce ovulation at a certain dose has been documented, without induction of progesterone withdrawal bleeding, and this approach has been nicknamed the clomiphene-citrate stair-step (CC-SS) protocol. The same principle has been found feasible before introducing gonadotropin therapy in CC-resistant PCOS patients. Our objective was to review the world literature on the CC-SS protocol and to summarize our own experience with extending the CC-SS approach to initiation of gonadotropin therapy. Studies on CC-SS protocol ( n = 4) have found that this approach leads to a significant reduction of the time to ovulation and to an increased ovulation rate. In our own retrospective case series, 18 CC-resistant PCOS patients initiated gonadotropin stimulation without induction of progesterone withdrawal bleeding, using the chronic low-dose regimen. The time to ovulation in the study group was 54.2 ± 6.2 days, while the estimated time to ovulation calculated according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence, the live birth rate was 38.9% (7/18). In summary, the CC-SS approach and its extension to the initiation of gonadotropin therapy results in considerable reduction of the time to ovulation, and favorable ovulation rates and reproductive outcome. Large-scale confirmation of these findings by properly designed randomized controlled trials may lead to a change of practice in the treatment of anovulatory infertility in PCOS patients, allowing simplification of treatment and a shorter time to ovulation and pregnancy.; Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. (© The Author(s), 2020.)

Hospital Aalborg, U., et al. (2021). Intravenous Immunoglobulin and Prednisolone for RPL After ART.
	No Results Available Drug: Human Intravenous Immunoglobulins, (Privigen (R), CLS Behring)|Drug: Prednisolone Tablets|Drug: Human Albumin Solution|Drug: Placebo tablet A normal live fetus at nuchal scan in ITT population|A normal live fetus at nuchal scan in PP population|Live birth rate in ITT population|Live birth rate in the PP population|A normal live fetus at nuchal scan among participants who become pregnant after embryo transfer in the ITT population|A normal live fetus at nuchal scan among participants who become pregnant after embryo transfer in the PP population|Maternal adverse reactions|Negative pregnancy test|Miscarriage rate|Rate of Abnormal karyotype in Miscarried fetuses|Rate of Stillbirth rate|Rate of Congenital deformities|Rate of Preterm birth|Rate of Low birth weight (BW)|Rate of Preeclampsia|Rate of Gestational diabetes|Rate of gestational hypertension|Rate of abnormal embryonic/fetal karyotype|Frequency of a boy Female Phase 2 74 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment CNPOBC2020|2020-000256-35|U1111-1273-8585 August 1, 2023

Hospital Adiyaman University, R. (2021). Effect of Laughter Yoga Therapy on Postpartum Depression.
	No Results Available Other: Laughter yoga Effect of Laughter Yoga therapy on postpartum Depression Female Not Applicable 104 Other Allocation: Randomized|Intervention Model: Factorial Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care lokman hekim September 10, 2021 Laughter yoga sessions, stretches and stretches, songs, clapping and body It starts with light warm-up techniques that include movements. These are to break down all kinds of inhibitions and It is aimed at developing the feelings of childlike play. breathing exercises lungs they are ready to laugh and are combined with the following series of laughing exercises. LY In order to provide group dynamics in therapy, the group should consist of at least 5-12 people. provided. Real laughter is often experienced during laughter meditation; it's contagious and may trigger laughter in other people in the group, hence the group can establish greater connections with its members. Laughter yoga sessions are always held at the same time and in the same place to encourage the participation of individuals.

Hospital, B. C. W. s. and H. Centre (2021). Pathways for Patient-centered Diagnosis and Management of Endometriosis-associated Deep Dyspareunia.
	No Results Available Device: Phallus Length Reducer|Other: Self-assessment of dyspareunia Acceptability of the phallus length reducer (PLR)|Severity of dyspareunia|Change in sexual function|Change in sexual distress|Change in level of general anxiety (GAD-7)|Change in level of general depression (PHQ-9)|Acceptability of self-measurement of dyspareunia|Validity of self-measurement of dyspareunia|Feasibility - Recruitment|Feasibility - Retention|Feasibility - Intervention Fidelity All Not Applicable 30 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Other H19-00294 December 31, 2021

Hospital Boston, C. s. (2024). IUD and Norethindrone Acetate for Treatment of Endometriosis.
	No Results Available Drug: norethindrone acetate (NETA)|Drug: Placebo Change in Pain-Physical functioning assessed by the BPI|Change in pain severity measured by Visual Analog Scale (VAS)|Change in pain measured by Biberoglu and Behrman patient ratings scale (B&B pain scale)|Change in Emotional functioning, assessed by the Beck Depression Inventory-II (BDI)|Change in Participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale (PGIC)|Change in high sensitivity C-reactive protein|Change in interleukin-8|Change in tumor necrosis factor alpha|Change in Tissue factor pathway inhibitor (TFPI)|Change in von Willebrand factor antigen|Change in Factor VIII activity|Change in soluble P-selectin|Change in interleukin-6 (IL-6)|Change in lipoprotein[a]|Change in Measure of arterial stiffness by pulse wave velocity|Change in Bone mineral density Z-scores by dual energy Xray absorptiometry (DXA)|Change in measures of central hypersensitization measured by quantitative sensory testing. Female Phase 2 80 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment IRB-P00037934 September 1, 2028

Hospital Erzincan, M. (2022). Use of Chitosan Powder in Loop Electrosurgical Excision Procedure.
	No Results Available Drug: Chitosan median early postoperative blood loss|Wound healing score Female Phase 4 130 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Prevention MUGLA-9 January 31, 2024

Hospital Gemelli, M., et al. (2021). Efficacy and Safety of SBRT in Oligo-metastatic/Persistent/Recurrent Ovarian Cancer.
	No Results Available Radiation: Stereotactic body radiotherapy Clinical complete response to SBRT by imaging|2-yr actuarial LC rate|2-yr progression-free survival|2-yr overall survival|treatment free interval|rate of toxicity|2-yr actuarial late toxicity free survival Female Not Applicable 200 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CE 07-14-2020 December 31, 2024

Hospital, H. (2022). Laser Treatment of Genito-urinary Syndrome in Women.
	No Results Available Procedure: Vaginal laser treatment|Device: sham|Device: laser system Visual analogue score on vaginal symptoms|histopathology|microbiology Female Not Applicable 160 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care Laser treatment December 31, 2026

Hospital Istanbul Medipol, U. (2021). Comparison of the Efficacy of Pharmacology and Non-pharmacological Treatment in Women With Primary Dysmenorrhea.
	No Results Available Other: Conservative and Non-conservative treatments Demographic Information Form|Visual Analogue Scale (VAS)|McGill Pain Questionnaire|Ultrasonography (US)|Menstrual Attitude Questionnaire Female Not Applicable 85 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 10840098-604.01.01-E.66761 December 10, 2021

Hospital Istanbul Medipol, U. (2021). Investigation of the Effect of Online Yoga Based Exercise Program on Women With Primary Dysmenorrhea.
	No Results Available Other: Exercise Program|Other: Education Program Sociodemographic Evaluation|Pain Intensity|Life Quality|Menstrual Attitude|Body Awareness|Satisfaction survey|Weight|Height Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 10840098-772.02-E.60605 January 30, 2022

Hospital Konya Meram, S. (2022). Comparison of Dydrogesterone and Micronized Progesterone Treatments in the Treatment of Threatened Miscarriage.
	No Results Available Drug: Duphastone Miscarriage rate Female Phase 4 140 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 351508 November 2024

Hospital Korea University, G., et al. (2023). Secondary Cytoreductive Surgery (CRS) in Patients With Relapsed Ovarian Cancer Who Have Progressed on PARP Inhibitor Maintenance.
	No Results Available Procedure: secondary cytoreductive surgery|Drug: chemotherapy progression-free survival|Overall survival Female Phase 2 124 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment KGOG3067 February 28, 2028

Hospital Massachusetts, G., et al. (2023). Vaginal lIve Biotherapeutic RANdomized Trial.
	No Results Available Drug: LC106|Drug: LC115|Drug: Placebo|Drug: Metronidazole Oral Detection of LBP strains by metagenomic sequencing|Adverse events|Kinetics of colonization|Recurrent BV by Amsel and Nugent criteria|Non-iners Lactobacillus dominance and abundance|Alpha and beta diversity of the microbial community|Proportion of participants reporting product was acceptable to use Female Early Phase 1 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment VMRC001 September 2024

Hospital Odense, U., et al. (2023). FRAGINOC Study: Screening and Geriatric Assessment and Intervention in Older Patients With Epithelial Ovarian Cancer.
	No Results Available Other: Comprehensive geriatric assessment and individualised physical training Interval Debulking Surgery|Frailty screening questionnaires|Completion of chemotherapy treatment|Effect of training: Physical capacity and endurance|Effect of training: Physical function and strength|Effect of physical training: Physical function in relation to basic mobility|Effect of physical training: Physical function in relation to balance|Effect of physical training: Clinical reported measurements|Effect of physical training: Self-reported measurements|Patient-reported outcomes measures (PROMs)|Frailty screening combined tool|Postoperative complications|Progression Free-Survival Female Not Applicable 300 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment OUHAgeCareOvarian December 31, 2027

Hospital Tampere, U., et al. (2023). Measuring Oncological Value of Exercise and Statin.
	No Results Available Behavioral: Guided physical exercise|Drug: Atorvastatin|Other: Independent exercise Time to cancer progression|Mortality|Hypoxia markers in serum (VEGF, HIF1-alpha, carboanhydrase IX, LADH)|Tolerability of treatment|Fat/muscle ratio as measured with impedance test|Physical performance with standardized muscle strength tests|Changes in tissue hypoxia|Changes in quality of life|Depressive symptoms|Severity of pain|Nutritional status|Relationship satisfaction All Phase 3 240 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2019-001982-34 December 31, 2027

Hospital The, M. and I. Foundation Rhode (2023). Mindful Movement for Pelvic Pain.
	No Results Available Other: Mindful Movement Change in Pelvic Pain Level|Impact on Quality of Life|Change in Kinesiophobia and Pain Catastrophizing Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 1979873|7141745 March 2024

Hospital Women's, C., et al. (2021). RCT of At-Home tDCS for Depression in Pregnancy.
	No Results Available Device: active tDCS|Other: workbook|Device: sham tDCS Depressive symptoms post treatment|Remission of depression|Depressive symptoms|Self-reported depressive symptoms|Self-reported anxiety symptoms|Maternal Quality of Life (QoL)|Health Service Use: Health System Costs|Health Service Use: Productivity Loss|Health Service Use: Participant Cost|Dyadic Relationship|Maternal Birth Outcomes|Neonatal Birth Outcomes|Maternal Child Relationship|Infant Temperament|Child Development Female Not Applicable 156 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment CTO Project ID: 3263 October 2026

Hou, C., et al. (2021). "A Comparison of Chemotherapy Used with and without Apatinib for Patients with Ovarian Carcinoma Who Progressed after Standard Regimens: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2021: 2292907.
	Objective: This meta-analysis was conducted to compare the therapeutic efficacy and clinical safety of the combination therapy of apatinib plus chemotherapy with that of chemotherapy alone in patients with refractory or recurrent ovarian carcinoma (OC).; Methods: Relevant randomized controlled trials (RCT) or case-control studies (CCS) were identified by searching Chinese and English databases up to October 31, 2020. The risk of methodological bias tool and Newcastle-Ottawa scale (NOS) were used to assess trial quality. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the therapeutic effects and adverse drug reactions. Subgroup analyses of study type, study sample size, dosage of apatinib, and chemotherapy regimen between treatment group and control group were performed. Publication bias was assessed by funnel plot symmetry, Begg-Mazumdar test, and Egger test. The robustness of our results was presented by removing the trial one by one.; Results: Fifteen eligible studies covering 1,020 patients were included in this review and meta-analysis. Among these studies, 8 were RCTs, and 7 were CCSs. Compared with chemotherapy alone, apatinib plus chemotherapy significantly increased objective response rate (OR = 3.55; 95% CI 2.31 to 5.47), disease control rate (OR = 3.04; 95% CI 2.12 to 4.36), and overall survival (OR = 5.03; 95% CI 3.16 to 6.90).; Conclusions: The combination treatment of apatinib plus chemotherapy provides better clinical benefits for OC patients when compared to chemotherapy alone and should be recommended for suitable patients with OC after the failure of standard regimens. However, further investigation into future large-scale prospective randomized research is still needed.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2021 Chao Hou et al.)

Hou, Q., et al. (2021). "Early response to neoadjuvant chemotherapy helps decrease recurrence rate of cervical cancer: a systematic review and meta-analysis." Annals of Palliative Medicine 10(6): 6092-6103.
	Background: Neoadjuvant chemotherapy has been used for treatment of cervical cancer for a long time; however, the role of early non-response on prognosis is still confusing. This study was designed to assess its impact on disease-free survival (DFS).; Methods: Databases "PubMed", "Embase" and the "Cochrane Library" were searched out through May 2020, and both random effects model and fixed effect model were employed to calculate the main pooled results. I2 and Cochrane Q test were used to test the heterogeneity among the studies. Funnel plot with Begg's and Egger's tests was used to assess the publication bias that may exist in the study. Sensitivity analysis was performed to detect the origin of the heterogeneity.; Results: A total of 1,349 articles were found at first; then, after several rounds of exclusion, we identified 8 articles with 9 studies which were accordant with the standards of the inclusion. A combined analysis was performed among the 1,462 responders and 490 non-responders. For 1-year DFS, sub-analysis showed hazard ratio (HR) was 0.25 (95% CI: 0.14-0.43) using RECIST criteria; and HR was 0.52 (95% CI: 0.36-0.75) using WHO criteria; Egger's test showed that P=0.35 for RECIST criteria and P=0.57 for WHO criteria; Begg's test showed P=0.34 for RECIST criteria and P=0.60 for WHO criteria. For 3-year DFS, HR was 0.26 (95% CI: 0.16-0.43) using RECIST criteria and was 0.47 (95% CI: 0.30-0.73) using WHO criteria. For 5-year DFS, HR was 0.26 (95% CI: 0.16-0.42) using RECIST criteria and was 0.49 (95% CI: 0.33-0.71) using WHO criteria.; Discussion: Early non-response to neoadjuvant chemotherapy was significantly associated with higher recurrence of cervical cancer. Prospective randomized studies are warranted to validate this finding.

Hou, T., et al. (2019). "Efficacy and safety of moxibustion in female infertility patients undergoing in vitro fertilization and embryo transfer: A systematic review protocol." Medicine 98(44): e17560.
	Introduction: The purpose of this paper is to evaluate the efficacy and safety of moxibustion in infertility females/women undergoing in vitro fertilization and embryo transfer (IVF-ET).; Methods and Analysis: We will electronically search PubMed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to moxibustion in female infertility patients undergoing IVF-ET will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The clinical total effective rate and the clinical pregnancy rate will be the primary outcomes. Ovulation rate, endometrial thickness, hormone level, traditional Chinese medicine (TCM) Syndrome Integral Scale and the adverse event will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), while dichotomous data will be expressed in the form of relative risk with 95% CIs.; Results: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of moxibustion in the treatment of female infertility patients undergoing IVF-ET.; Conclusion: This review will provide evidence to judge for judging whether moxibustion is effective in treating female infertility patients undergoing IVF-ET.; Systematic Review Registration: PROSPERO, CRD42019135593.

Houston Charlotte, G., et al. (2024). "A Cost Savings Analysis of Topical Estrogen Therapy in Urinary Tract Infection Prevention Among Postmenopausal Women." Urology practice 11(2): 257-266.
	Introduction: UTIs are some of the most common infections in geriatric patients, with many women experiencing recurrent infections after menopause. In the US, annual UTI-related costs are $2 billion, with recurrent infections creating a significant economic burden. Given the data published on topical estrogen in reducing the number of infections for postmenopausal women with recurrent UTI, we sought to evaluate how this would translate to cost savings.; Methods: We performed a systematic literature review of UTI reduction secondary to topical estrogen utilization in postmenopausal female patients. The cost per UTI was determined based on published Medicare spending on UTI per beneficiary, weighted on reported likelihood of complicated and resistant infections. For a patient with recurrent infections, topical estrogen therapy reported on average can reduce infections from 5 to 0.5 to 2 times per person per year.; Results: At a calculated cost per UTI of $1222, the reduction in UTI spending can range between $3670 and $5499 per beneficiary per year. Per-beneficiary spending on topical estrogen therapies was $1013 on average ($578-$1445) in 2020. After including the cost of the therapy, overall cost savings for topical estrogen therapies were $1226 to $4888 annually per patient.; Conclusions: Topical estrogens are a cost-conscious way to improve the burden of UTI on postmenopausal women with the potential for billions of dollars in Medicare savings. System-wide efforts should be made to have these therapies available as prophylaxis for postmenopausal patients and to ensure they are affordable for patients.

Howard Louise, M., et al. (2022). "Perinatal mental health services in pregnancy and the year after birth: the ESMI research programme including RCT." Programme Grants for Applied Research.
	Background: It is unclear how best to identify and treat women with mental disorders in pregnancy and the year after birth (i.e. the perinatal period).; Objectives: (1) To investigate how best to identify depression at antenatal booking [work package (WP) 1]. (2) To estimate the prevalence of mental disorders in early pregnancy (WP1). (3) To develop and examine the efficacy of a guided self-help intervention for mild to moderate antenatal depression delivered by psychological well-being practitioners (WP1). (4) To examine the psychometric properties of the perinatal VOICE (Views On Inpatient CarE) measure of service satisfaction (WP3). (5) To examine the clinical effectiveness and cost-effectiveness of services for women with acute severe postnatal mental disorders (WPs 1–3). (6) To investigate women’s and partners’/significant others’ experiences of different types of care (WP2).; Design: Objectives 1 and 2 – a cross-sectional survey stratified by response to Whooley depression screening questions. Objective 3 – an exploratory randomised controlled trial. Objective 4 – an exploratory factor analysis, including test–retest reliability and validity assessed by association with the Client Satisfaction Questionnaire contemporaneous satisfaction scores. Objective 5 – an observational cohort study using propensity scores for the main analysis and instrumental variable analysis using geographical distance to mother and baby unit. Objective 6 – a qualitative study.; Setting: English maternity services and generic and specialist mental health services for pregnant and postnatal women.; Participants: Staff and users of mental health and maternity services.; Interventions: Guided self-help, mother and baby units and generic care.; Main Outcome Measures: The following measures were evaluated in WP1(i) – specificity, sensitivity, positive predictive value, likelihood ratio, acceptability and population prevalence estimates. The following measures were evaluated in WP1(ii) – participant recruitment rate, attrition and adverse events. The following measure was evaluated in WP2 – experiences of care. The following measures were evaluated in WP3 – psychometric indices for perinatal VOICE and the proportion of participants readmitted to acute care in the year after discharge.; Results: WP1(i) – the population prevalence estimate was 11% (95% confidence interval 8% to 14%) for depression and 27% (95% confidence interval 22% to 32%) for any mental disorder in early pregnancy. The diagnostic accuracy of two depression screening questions was as follows: a weighted sensitivity of 0.41, a specificity of 0.95, a positive predictive value of 0.45, a negative predictive value of 0.93 and a likelihood ratio (positive) of 8.2. For the Edinburgh Postnatal Depression Scale, the diagnostic accuracy was as follows: a weighted sensitivity of 0.59, a specificity of 0.94, a positive predictive value of 0.52, a negative predictive value of 0.95 and a likelihood ratio (positive) of 9.8. Most women reported that asking about depression at the antenatal booking appointment was acceptable, although this was reported as being less acceptable for women with mental disorders and/or experiences of abuse. Cost-effectiveness analysis suggested that both the Whooley depression screening questions and the Edinburgh Postnatal Depression Scale were more cost-effective than with the Whooley depression screening questions followed by the Edinburgh Postnatal Depression Scale or no-screen option. WP1(ii) – 53 women with depression in pregnancy were randomised. Twenty-six women received modified guided self-help [with 18 (69%) women attending four or more sessions] and 27 women received usual care. Three women were lost to follow-up (follow-up for primary outcome: 92%). At 14 weeks post randomisation, women receiving guided self-help reported fewer depressive symptoms than women receiving usual care (adjusted effect size −0.64, 95% confidence interval −1.30 to 0.06). Costs and quality-adjusted life-years were similar, resulting in a 50% probability of guided self-help being cost-effective compared with usual care at National Institute for Health and Care Excellence cost per quality-adjusted life-year thresholds. The slow recruitment rate means that a future definitive larger trial is not feasible. WP2 – qualitative findings indicate that women valued clinicians with specialist perinatal expertise across all services, but for some women generic services were able to provide better continuity of care. Involvement of family members and care post discharge from acute services were perceived as poor across services, but there was also ambivalence among some women about increasing family involvement because of a complex range of factors. WP3(i) – for the perinatal VOICE, measures from exploratory factor analysis suggested that two factors gave an adequate fit (comparative fit index = 0.97). Items loading on these two dimensions were (1) those concerning aspects of the service relating to the care of the mother and (2) those relating to care of the baby. The factors were positively correlated (0.49; p < 0.0001). Total scores were strongly associated with service (with higher satisfaction for mother and baby units, 2 degrees of freedom; p < 0.0001) and with the ‘gold standard’ Client Service Questionnaire total score (test–retest intraclass correlation coefficient 0.784, 95% confidence interval 0.643 to 0.924; p < 0.0001). WP3(ii) – 263 of 279 women could be included in the primary analysis, which shows that the odds of being readmitted to acute care was 0.95 times higher for women who were admitted to a mother and baby unit than for those not admitted to a mother and baby unit (0.95, 95% confidence interval 0.86 to 1.04; p = 0.29). Sensitivity analysis using an instrumental variable found a markedly more significant effect of admission to mother and baby units ( p < 0.001) than the primary analysis. Mother and baby units were not found to be cost-effective at 1 month post discharge because of the costs of care in a mother and baby unit. Cost-effectiveness advantages may exist if the cost of mother and baby units is offset by savings from reduced readmissions in the longer term.; Limitations: Policy and service changes had an impact on recruitment. In observational studies, residual confounding is likely.; Conclusions: Services adapted for the perinatal period are highly valued by women and may be more effective than generic services. Mother and baby units have a low probability of being cost-effective in the short term, although this may vary in the longer term.; Future Work: Future work should include examination of how to reduce relapses, including in after-care following discharge, and how better to involve family members.; Trial Registration: This trial is registered as ISRCTN83768230 and as study registration UKCRN ID 16403.; Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research ; Vol. 10, No. 5. See the NIHR Journals Library website for further project information. (Copyright © 2022 Howard et al. This work was produced by Howard et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.)

Howard, Z., et al. (2022). "A group program for overweight and obese women with urinary incontinence (ATHENA): an implementation-effectiveness hybrid type 3 study." International Urogynecology Journal 33(4): 991-1000.
	Introduction and hypothesis: Supervised pelvic floor muscle training (PFMT), weight loss and exercise are recommended for overweight/obese women with urinary incontinence (UI). This study aimed to implement and evaluate the feasibility, acceptability and effectiveness of a 12-week group exercise and healthy eating program (ATHENA) for overweight/obese women with UI. Method(s): This study, using an implementation-effectiveness hybrid type 3 design, was conducted within a Women's Health Physiotherapy outpatient service at an Australian tertiary public hospital. Intervention feasibility and acceptability were assessed through process evaluation of implementation, while clinical effectiveness was assessed via pre-/post-clinical and quality of life surveys. Process data were analyzed using descriptive statistics and effectiveness data were compared pre-/post-intervention using inferential statistics. Result(s): Of 156 eligible patients, 37 (24%) agreed to participate; 29 (78%) completed the ATHENA program. Median (IQR) age and body mass index were 53 (47-65) years and 30.8 (29.1-34.8) kg/m2 respectively. ATHENA was feasible to implement, with all components delivered as intended and high participant satisfaction. Ninety-seven percent of participants reported improved UI symptoms (global rating of change) and significant improvements in overall pelvic floor dysfunction and quality of life utility scores (p = 0.001). While weight did not change, significant improvements were found in body-food choice congruence (intuitive eating scale-2; p < 0.01). Conclusion(s): The ATHENA intervention was feasible, acceptable and clinically effective for overweight and obese women with urinary incontinence at a tertiary public hospital in Australia. Further research into longer term outcomes and the cost effectiveness of this group intervention is recommended. Trial registration: N/A. Ethics approval, HREC/2018/QGC/46582, date of registration 14/11/2018.Copyright © 2021, Crown.

Hroncová, M. (2023). "Pelvic pain in women after childbirth and physiotherapy." Ceska gynekologie 88(3): 214-220.
	Objective: There are many types of pelvic pain. Pelvic plexus pain, coccyx pain, pain from episiotomy scars, and vulvodynia are frequently seen in postpartum women. The aim of this study was to conduct a systematic review of studies on pelvic pain in postpartum women to assess the effect of physiotherapy interventions on each type of pain.; Methods: A comprehensive literature review was conducted by searching on PubMed, Ovid Embase and Scopus Web of Science using the key words - pelvic pain, women after childbirth, pelvic girdle pain, coccygodynia, episiotomy, vulvodynia, and physiotherapy. The author reviewed all the identified articles and selected articles for inclusion according to relevance to the topic.; Conclusion: Based on the analysis of the above studies, it can be concluded that a comprehensive physiotherapy designed for postpartum women that includes manual techniques, behavioral techniques, relaxation of hypo-tonic and shortened muscles and strengthening of hypotonic muscles can positively affect a wide range of pain and associated dysfunctions of the pelvic floor and trunk muscles.

https, et al. (2021). "Acupressure for Cancer-fatigue in Ovarian Cancer Survivor (AcuOva) Study: A community-based clinical trial study protocol examining the impact of self-acupressure on persistent cancer-related fatigue in ovarian cancer survivors." Contemporary Clinical Trials 107: 106477.
	Background Persistent cancer-related fatigue is one of the most common and burdensome symptoms experienced by ovarian cancer survivors. Despite the high burden of fatigue in ovarian cancer survivors, there are few available treatments. Previous research has shown self-acupressure to be a safe method for improving persistent fatigue, sleep, and quality of life among fatigued breast cancer survivors, yet there are no studies examining self-acupressure for fatigue in ovarian cancer survivors. Methods A three group parallel, randomized controlled trial will be conducted to evaluate the efficacy of self-acupressure taught and delivered via a patient-designed, custom-built mobile app ("MeTime") and accompanying hand-held device ("AcuWand") to help guide correct pressure application. A sample of 165 ovarian cancer survivors, who have completed primary cancer treatment will be recruited from tumor registries in Michigan and Los Angeles. Participants will be mailed a tablet preloaded with the app and a device, and all visits will be conducted remotely. Participants will be randomized to 6-weeks of daily self-acupressure via the app and device, or a sham app and device, or no care group. Self-report measures will be completed at baseline, 6-weeks (post-intervention), 3-, and 6-months. Primary outcome is the Brief Fatigue Inventory; secondary outcomes are sleep, quality of life, and symptoms commonly associated with persistent fatigue. Discussion An app based self-acupressure treatment may be an easily-accessible and inexpensive treatment to reduce fatigue in ovarian cancer survivors. The results of the study will provide information on the possible benefits of app-based self-acupressure for fatigue in ovarian cancer survivors. Trial registration: This study is registered at ClinicalTrials.gov Identifier: NCT03763838, date registered on December 4, 2018. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Htut Thura, W., et al. (2022). "Meta-analysis of randomized controlled trials on primary ambulatory thromboprophylaxis in patients with ovarian cancer receiving chemotherapy." Proceedings (Baylor University. Medical Center) 35(3): 332-336.
	Ovarian cancer (OC) is highly associated with venous thromboembolism (VTE). The OC cells stimulate thrombin generation, and chemotherapy potentiates the prothrombotic effect of cancer cells by damaging endothelium and enhancing hypercoagulability. Recently, primary ambulatory thromboprophylaxis (PATP) has been studied as a potential treatment in cancer patients undergoing chemotherapy with an aim of reducing the incidence of VTE and potentially prolonging survival. A meta-analysis was performed of randomized controlled trials of PATP vs control in patients with OC receiving chemotherapy. The primary outcome measure was the incidence of VTE. The secondary outcome measure was the incidence of major bleeding complications. Two articles published between 2012 and 2020 fulfilled selection criteria. The incidence of VTE was 0.9% in the PATP group and 1.8% in the control group. However, the pooled risk ratio was not statistically significant at 0.69 (95% CI: 0.08 to 5.67; P = 0.73). The absolute risk difference was -0.03 (95% CI, -0.17 to 0.11; P = 0.66). There was no statistically significant reduction in VTE by providing PATP to patients with OC receiving chemotherapy. Routine PATP should not be recommended in ambulatory OC patients. Future randomized trials are necessary to define the high-risk subset of OC patients who may benefit from PATP. (Copyright © 2022 Baylor University Medical Center.)

Hu, J., et al. (2023). "Evidenced summary for comprehensive detumescence treatment for lower limb lymphedema in patients with gynecological malignant tumor." Chinese Journal of Practical Nursing 39(15): 1167-1174.
	Objective To evaluate and summarize the relevant evidence of comprehensive detumescence treatment of lower limb lymphedema in patients with gynecological malignant tumors, and to provide evidence-based basis for clinical intervention of comprehensive detumescence treatment of lymphedema. Methods This study was an evidence - based nursing research. Databases such as BMJ Best Practice, UpToDate, PubMed, CNKI, Wanfang and other domestic and foreign databases, as well as websites such as the Australian Lymphology Society, the International Lymphedema, and the European Clinical Oncology Association were searched for relevant evidence and evaluation of comprehensive treatment of gynecological malignant tumor-related lower limb lymphedema. The search time was from the establishment of the database to April 1, 2022. Results A total of 18 articles were included, including 2 guidelines, 5 systematic reviews, 4 expert consensus, 2 evidence summaries, 4 randomized controlled trials and 1 best practice. Twenty-eight evidence were summarized from 7 aspects: treatment cycle and edema stage, free-hand lymphatic drainage, graduated compression stockings, skin care, elastic socks, functional exercise and health education. Conclusions The evidence summarized in this study can provide reference for clinical medical staff to formulate comprehensive treatment plans for lower limb lymphedema. Evidence-based practice should consider the individual status of patients and clinical scenarios, and provide personalized comprehensive treatment plans for patients with lower limb lymphedema of gynecological malignant tumors as soon as possible to improve the quality of life of patients.Copyright © 2023 The authors.

Hu, J., et al. (2021). "The best evidence for the prevention and management of lower extremity deep venous thrombosis after gynecological malignant tumor surgery: A systematic review and network meta-analysis." Journal of B.U.ON. 26(6): 2365-2372.
	Purpose: To search and obtain the relevant evidence of prevention and management of lower extremity deep venous thrombosis after gynecological malignant tumor operation, and to summarize the relevant evidence. Method(s): We searched JBI evidence summary, up to date, the national comprehensive cancer network of the United States, the guide library of the National Institute of clinical medicine of the United Kingdom, PubMed, the Chinese biomedical literature database, CNKI, Wanfang and other relevant evidence on the prevention and management of deep venous thrombosis in patients with gynecological malignant tumors. It includes clinical practice guidelines, best practice information book, expert consensus, evidence summary, original research, etc. The retrieval time limit is from database establishment to August 20, 2021. Two researchers independently evaluated the literature quality, combined with professional judgment, and extracted the literature that met the standards. Result(s): Finally, 18 articles were included, including 8 guidelines, 3 evidence summaries, 4 systematic evaluations, 2 expert consensus and 1 best practice information volume. A total of 26 pieces of best evidence on the prevention and management of postoperative venous thrombosis in gynecological malignant tumors were summarized. This included risk assessment, drug prevention, mechanical prevention, management strategy and health education. Conclusion(s): This study summarized the best evidence of risk, prevention and health management of deep venous thrombosis in postoperative patients with gynecological malignant tumors, so as to provide evidence-based basis for clinical nurses and improve nursing level.Copyright © 2021 Zerbinis Publications. All rights reserved.

Hu, J., et al. (2021). "Efficacy and safety of Buzhong Yiqi Decoction in improving cancer-related fatigue and immunity of cervical carcinoma patients: A protocol of randomized controlled trial." Medicine 100(49): e27938.
	Background: Cancer-related fatigue (CRF) is essentially universal in cervical carcinoma patients. It develops rapidly, with physical and mental manifestations including generalized weakness, diminished concentration or attention, and it has a negative impact in overall quality of life. Buzhong Yiqi Decoction (BYD), a classical Chinese medical prescription, could be used for allergic rhinitis, gut microbiota disorders, and chronic obstructive pulmonary disease. We preliminarily found that BYD could relieve CRF in cervical carcinoma patients. However, there are few trials on whether BYD could relieve CRF and improve immunity in cervical carcinoma patients.; Methods: This is a double-blinded, randomized, controlled clinical trial. From December 1, 2021 to May 31, 2022, cervical carcinoma patients with CRF will be assessed for randomization into treatment group (BYD) and control group (BYD simulation) in a 1:1 ratio. The outcomes are cancer fatigue scale, self-rating anxiety scales, self-rating depression scales, Pittsburgh sleep quality index, and immunity index (CD3+, CD4+, and CD8+) before and after the treatment. Statistical analysis will be performed using SPSS v22.0 software.; Results and Conclusions: The study will clarify the efficacy and safety of BYD in improving CRF and immunity in cervical carcinoma patients.; Trial Registration: OSF Registration number: DOI 10.17605/OSF.IO/QFNMD.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hu, J., et al. (2021). "Complementary and Alternative Medicine for the Treatment of Abnormal Endometrial Conditions in Women with PCOS: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Evidence-based complementary and alternative medicine : eCAM 2021: 5536849.
	Background: Endometrial lesions in patients with polycystic ovary syndrome (PCOS) exhibit complex pathological features, and these patients are at risk of both short-term and long-term complications. Complementary and alternative medicine (CAM), which is gradually becoming more accepted and is believed to be clinically effective, claims to be promising for treating PCOS, and thus its effect on the abnormal endometrium of PCOS patients should be assessed. The present meta-analysis sought to evaluate the efficacy and safety of CAM in treating endometrial lesions in patients with PCOS.; Methods: Randomized trials on CAM were identified in four Chinese and seven English-language databases from their establishment to January 2020. The present study included patients diagnosed with PCOS and abnormal endometrial conditions who underwent CAM therapy independently or in combination with traditional western medicine. Data were extracted, and the Cochrane "risk of bias" tool was used to assess methodological quality. Effects were expressed as the relative risk (RR) or mean difference (MD/SMD) with 95% confidence interval (CI) as calculated with Rev Man 5.3.; Results: A total of 13 randomized controlled trials were included, involving 1,297 PCOS patients treated for endometrial abnormalities. Methodological quality was generally unclear or had a low risk of bias. The trials tested four different types of CAM therapies (i.e., traditional Chinese medicine treatment, acupuncture treatment, traditional Chinese medicine in combination with western medicine treatment, and acupuncture in combination with western medicine treatment). CAM treatment could significantly reduce the endometrial thickness in PCOS patients compared to western medicine alone (SMD -0.88, 95% CI [-0.12, -0.57]; I 2 = 64%). Compared with clomiphene treatment for the induction of ovulation, CAM treatment showed a clear improvement in endometrial thickness during ovulation (SMD 2.03, 95% CI [1.64, 2.02]; I 2 = 48%). Moreover, CAM was more effective than western medicine alone in reducing the endometrial spiral artery pulsatility index. No significant difference was seen between CAM and traditional treatment when these were used to improve traditional Chinese medicine syndrome scores. Acupuncture alone or traditional Chinese medicines (taken orally) in combination with western medicine significantly increased the pregnancy rate of PCOS patients (RR 1.59, 95% CI [1.30, 1.93]; I 2 = 51%, P < 0.00001), and CAM was more effective than western medicine alone for improving hormone levels. No serious adverse events were reported in 11 of the 13 trials.; Conclusions: CAM may effectively ameliorate the endometrial condition of PCOS patients, and it can regulate the level of hormone secretion to increase the ovulation rate and the pregnancy rate.; Competing Interests: The authors declare that they have no relevant conflicts of interest. (Copyright © 2021 Jiayu Hu et al.)

Hu, L., et al. (2024). "Stem cell therapy for premature ovarian insufficiency: a systematic review and meta-analysis of animal and clinical studies." Archives of Gynecology and Obstetrics 309(2): 457-467.
	Purpose: The aim of this systematic review and meta-analysis is to evaluate the efficacy of stem cell therapy in mouse models of POI and patients with POI. Method(s): The PubMed, Web of Science, and Embase databases were searched from inception to February 2022 for relevant animal and clinical studies. The reference lists of the included reviews were manually searched to identify additional eligible studies. Data were independently extracted by two investigators, and disagreements were resolved by discussion. SYRCLE's risk of bias tool and the MINORS tool were used to assess the quality of animal and clinical studies by two independent investigators. All statistical analyses were conducted using Review Manager 5.3 software. Result(s): A total of twenty animal studies and six clinical studies were included in this meta-analysis. In animal studies, the results showed that stem cells could improve hormone levels, follicle count, estrous cycle and pregnancy outcome. For hormone levels, stem cells increased serum E2 and AMH levels and decreased serum FSH and LH levels compared with the control group (serum E2 level: SMD: 5.05, 95% CI 4.21-5.90, P < 0.00001; serum AMH level: SMD: 4.42, 95% CI 3.06-5.79, P < 0.00001; serum FSH level: SMD: - 3.79, 95% CI - 4.87 to - 2.70, P < 0.00001; serum LH level: SMD: - 1.31, 95% CI - 1.65 to - 0.96, P < 0.00001). All follicle counts, except for the antral follicle count, were significantly changed compared with the control group. (primordial follicle count: SMD: 4.61, 95% CI 3.65-5.56, P < 0.00001; primary follicle count: SMD: 3.35, 95% CI 1.08-5.63, P = 0.004; secondary follicle count: SMD: 3.23, 95% CI 1.92-4.55, P < 0.00001; total follicle count: SMD: 4.84, 95% CI 2.86-6.83, P < 0.00001; oocyte count: SMD: 7.56, 95% CI 5.92-9.20, P < 0.00001; atretic follicle count: SMD: - 1.79, 95% CI - 2.59 to - 1.00, P < 0.00001). For the estrous cycle, stem cell therapy increased the number of estrous cycles (WMD: 2.72, 95% CI 2.07-3.37, P < 0.00001) and decreased the duration of the estrous cycle (WMD: - 1.26, 95% CI - 1.84 to - 0.69, P < 0.0001) compared with the control group. For pregnancy outcomes, stem cell therapy increased the fertility rate (RR: 3.00, 95% CI 1.74-5.17, P < 0.0001) and litter size (WMD: 3.82, 95% CI 0.36-7.28, P = 0.03) compared with the control group. In animal studies, the asymmetric funnel plot of serum E2 and FSH levels indicated the possibility of publication bias. Unpublished and negative studies may be the source of publication bias. In clinical studies, the results showed that stem cell therapy could decrease serum FSH level (MD: - 30.32, 95% CI - 59.03 to - 1.01, P = 0.04) and increase AFC (MD: 1.07, 95% CI 0.70-1.43, P < 0.00001), pregnancy rate (RD: 0.19, 95% CI 0.04-0.34, P = 0.01) and live birth rate (RD: 0.19, 95% CI 0.07-0.31, P = 0.001) in POI patients. In addition, there was no significant difference in menstrual function regained (RD: 0.22, 95% CI - 0.03-0.46, P = 0.09), oocytes retrieved (MD: 1.00, 95% CI - 0.64-2.64, P = 0.23) and embryos (MD: 0.80, 95% CI - 0.15-1.76, P = 0.10) between different groups. Conclusion(s): This meta-analysis suggested that stem cell therapy might be effective in POI mouse models and patients and could be considered a potential treatment to restore fertility capability in POI patients.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Hu, M., et al. (2024). "Modified Xiaoyao powder for postpartum depression: A systematic review and meta-analysis." Journal of Traditional Chinese Medical Sciences 11(1): 120-130.
	Objective: To evaluate the effectiveness and safety of modified Xiaoyao powder for postpartum depression (PPD) by conducting a systematic review of randomized controlled trials (RCTs). Method(s): The Chinese National Knowledge Infrastructure Databases (CNKI), the Chinese Scientific Journals Database (VIP), Wanfang, Google Scholar, the SinoMed, Embase, Cochrane Library, and PubMed databases were searched from their inception to April 25, 2023. The Cochrane Risk of Bias tool was used to assess the quality of the trials. We applied the risk ratio to present dichotomous data and the mean difference to present continuous data. Data with similar characteristics were pooled for meta-analysis and heterogeneity was assessed using I2. Result(s): This review included 35 trials involving 2848 participants. The quality of the included studies was low (unclear randomization processes and insufficient reporting of blinding). Participants treated with modified Xiaoyao powder plus Western medicine showed lower Hamilton Depression Scale (HAMD) depression score than those who used Western medicine alone (mean difference = -2.15; 95% confidence interval:-2.52 to 1.78; P <.00001), and higher effective rate (relative risk = 1.19; 95% confidence interval: 1.15 to 1.24; P <.00001), When comparing modified Xiaoyao alone with Western medicine, the HAMD depression score remained low, however, the efficacy rate was higher in the modified Xiaoyao group. Regarding adverse events, the modified Xiaoyao group reported weight gain, nausea, and diarrhea, but no severe adverse events were reported. Conclusion(s): Modified Xiaoyao may help relieve depression in PPD when used alone or in combination with Western medicine, with minor side effects. Therefore, future high-quality, large-sample size RCTs are warranted.Copyright © 2024 Beijing University of Chinese Medicine

Hu, S., et al. (2022). "Effects of Intrauterine Infusion of Autologous Platelet-Rich Plasma in Women Undergoing Treatment with Assisted Reproductive Technology: a Meta-Analysis of Randomized Controlled Trials." Geburtshilfe und Frauenheilkunde 83(4): 453-462.
	Purpose This meta-analysis was conducted to systematically retrieve relevant randomized controlled trials (RCTs) and evaluate the effects of intrauterine infusion of autologous platelet-rich plasma (PRP) in women with thin endometrium, implantation or pregnancy failure undergoing treatment with assisted reproductive technology (ART). Methods We conducted a systematic review and meta-analysis of the retrieved RCTs. Studies on the intrauterine infusion of PRP in women undergoing treatment with ART that were published in PubMed, the Cochrane library, Web of Science, and Embase from inception until June 2022 were included. The data were extracted and analyzed independently using the fixed-effects or random-effects model according to heterogeneity. Results Seven RCTs involving 861 patients (435 in the intervention group and 426 in the control group) were included. The rates of clinical pregnancy (risk ratio [RR]: 2.51; 95% confidence interval [CI]: 2.0-3.13; P < 0.00001), chemical pregnancy (RR: 1.96; 95% CI: 1.58-2.45; P < 0.00001), live births (RR: 7.03; 95% CI: 3.91-12.6; P < 0.00001), and implantation (RR: 3.27; 95% CI: 1.42-7.52; P = 0.005) were significantly higher in the women who received PRP infusion than in the control group. No significant differences were noted in the miscarriage rate (RR: 0.98; 95% CI: 0.39-2.42; P = 0.96) between the two groups. Conclusion In summary, intrauterine infusion of PRP may be an effective therapy for women with thin endometrium and recurrent implantation failure (RIF) undergoing treatment with ART. More population-based RCTs are warranted to verify the efficacy of our evidence.; Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest. (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Hu, T. and X. Wan (2021). "Clinical value of chemoradiotherapy in patients with endometrial cancer based on health informatics: A meta-analysis." Acta Medica Mediterranea 37(2): 1289-1295.
	Objective: Based on the meta-analysis of health informatics, the effects of combined chemoradiotherapy and radiotherapy alone on postoperative survival rate and complications of endometrial cancer patients were compared. Method(s): Study engineering and computer by health interest rates in ten thousand medi cal, PubMed database, domestic research on medical journals such as health and biomedical literature database for information retrieval, the direction of radiation in the combined chemotherapy in patients with endometrial carcinoma postoperative survival rate and the influence of complications such as indicators of health information related literature, on the basis of health informatics chosen Rev Man 5.2 software for Meta analysis. Result(s): According to the research object,method, disease type and other criteria,the retrieval literatures were screened,and a total of 7 literatures that met the criteria were finally included, with low publication bias. Meta analysis results showed that the 5-year OS,5-year progression-free rate and treatment complication rate of the radiotherapy combined with chemotherapy group were all higher than those of the radiotherapy alone group, and the 5-year recurrence rate of the radiotherapy combined with chemotherapy group was significantly lower than that of the radiotherapy alone group, with statistically significant differences (P<0.05). The sensitivity test results showed that the heterogeneity of the literature was small and had high reference value. Conclusion(s): Radiotherapy in combination with chemotherapy can obviously reduce postoperative recurrence rate, endometrial cancer patients can prolong the overall survival and progression-free rate at the same time,is worth popularization and application, but the combination therapy may increase the risk of patients with postoperative complications, is a new challenge in the field of health care, is creating a new era in medical areas must overcome one difficulty, should actively learn the new complication protection knowledge and skills, adopt effective protective measures to reduce the incidence of complications and complications for patients life security, create a new era of the radiation and chemotherapy treatment.Copyright © 2021 A. CARBONE Editore. All rights reserved.

Hu, T.-M., et al. (2022). "Effectiveness of aromatherapy for intrapartum and postpartum emotional problems among parturient women: A meta-analysis of randomized controlled trials." Japan journal of nursing science : JJNS 19(3): e12471.
	Aim: Perinatal negative emotions are common in parturient women, but the problems are often ignored. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that investigated the effectiveness of aromatherapy for intrapartum anxiety (IPA) and postpartum emotional symptoms (PES).; Methods: We searched PubMed, Embase, Cochrane library, and ClinicalTrials.gov to identify suitable RCTs for analysis, and the study was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.; Results: Nine RCTs were included. The meta-analysis showed aromatherapy reduced IPA during the early to active phase (standardized mean difference [SMD]: -1.56 [-2.55, -0.61]) and during the transition phase (SMD: -3.30 [-4.97, -1.63]) when compared with controls. For the postpartum period, the meta-analyses showed a reduction of postpartum depression (PPD) at week 2 (SMD: -0.43 [-0.82, -0.03]), and a non-significant trend toward the reduction of PPD at weeks 4-6 (SMD: -0.70 [-1.40, 0.01]).; Conclusion: Our study found some evidence supporting the effectiveness of aromatherapy in reducing intrapartum anxiety and PES. We recommend the optional use of aromatherapy for intrapartum and postpartum care. (© 2022 Japan Academy of Nursing Science.)

Hu, X., et al. (2020). "Effects of exercise therapy for pregnancy-related low back pain and pelvic pain: A protocol for systematic review and meta-analysis." Medicine 99(3): e17318.
	Background: Pregnancy-related low back pain (PLPB) and pelvic pain (PP) are common in pregnancy. In spite of its high prevalence rate, treatment of the disorder is a challenging topic. Women commonly utilize complementary exercise therapies such as yoga, motor control exercises, breathing exercises, core stability exercise, pelvic stability exercise, and so on to manage their symptoms. However, it is currently unknown whether exercise produces more beneficial effects than other treatment in patients with PLPB and PP. The aim of this study is to explore the therapeutic effect of exercise for pregnancy-related low back pain and PP.; Methods: This review will only include randomized controlled trials. Published articles from July 1999 to July 2019 will be identified using electronic searches. Search strategy will be performed in 3 English databases, 1 Chinese database, and the World Health Organization International Clinical Trials Registry Platform. Two reviewers will screen, select studies, extract data, and assess quality independently. The methodological quality including the risk of bias of the included studies will be evaluated using a modified assessment form, which is based on Cochrane assessment tool and Physiotherapy Evidence Database scale. Review Manager Software (Revman5.3) will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. We will use GRADE system to evaluate the quality of our evidence.; Results: We will provide some more practical and targeted results investigating the effect of exercise therapy (ET) for PLPB and PP in the current meta-analysis. Meanwhile, we will ascertain study progress of ET for PLPB and PP and find out defects or inadequacies of previous studies, so that future researchers could get beneficial guidance for more rigorous study.; Conclusion: The stronger evidence about PLPB and PPs rehabilitative effect and safety will be provided for clinicians and policymakers.; Systematic Review Registration: PROSPERO CRD 42017075099.

Hu, Y., et al. (2021). "Interventions for vaginal bleeding irregularities with contraceptive implant." Cochrane Database of Systematic Reviews(3).
	- Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effectiveness and safety of different treatments compared to no treatment or placebo for vaginal bleeding irregularities associated with the use of contraceptive implants.

hua, y. and z. yuan (2023). "The Significance of noninvasive therapies for cervical infection of high-risk human papilloma virus : A systematic review and meta-analysis."
	
Huan, T., et al. (2021). "Effects of transcutaneous tibial nerve stimulation on female with Overactive Bladder Syndrome in Multiple Sclerosis: A protocol for a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Huan, Y. U., et al. (2023). "Efficacy and Safety of Immune Checkpoint Inhibitors on Advanced Cervical Cancer: A Systematic Review and Meta-analysis."
	
Huang, A., et al. (2024). "Effects of a Pelvic Yoga Program on Genitourinary Quality of Life in Midlife and Older Women with Urinary Incontinence: a Multisite Randomized Trial." Journal of Neurosurgical Anesthesiology 36(1): 1263-1264.
	Objective: Pelvic yoga has been recommended as a complementary behavioral treatment strategy for women with genitourinary symptoms such as urinary incontinence that frequently emerge in midlife, but there is little evidence of its impact on women's genitourinary quality of life (QOL). We examined changes in genitourinary QOL among midlife and older women in a randomized trial of a group-based pelvic yoga program versus non-specific physical conditioning program for incontinence. Design(s): The Lessening Incontinence with Low-impact Activity (LILA) study is a multisite trial of a group-based yoga program designed by an expert yoga and clinician panel to improve pelvic function in midlife and older women. Ambulatory women aged 45 or older with incontinence were recruited from the general communities surrounding three study sites in California in 2019-2022. Eligible women were randomly assigned to a therapeutic yoga program consisting of twice weekly group instruction by trained yoga instructors and once weekly individual practice of study-specific Hatha yoga techniques for 3 months, versus a general physical conditioning program involving equivalent-time group instruction and individual practice of skeletal muscle stretching and strengthening exercises. Linear mixed models examined change in scores on multiple validated self-report measures of genitourinary symptom bother or quality of life over 3 months, including the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC), adjusting for site and intervention cohort. Result(s): Among the 240 participants randomized (121 to yoga, 119 to physical conditioning), mean age was 62.0 (+/-8.7) years (total range 45 to 90 years), and 40% self-identified as racial or ethnic minorities (14% Latina/Hispanic, 6% African American, 16% Asian American, 4% multiracial). At baseline, mean scores on genitourinary QOL measures were 38.8 (+/-19.2) for the UDI-6, 101.0 (+/-.7) for the IIQ, and 3.4 (+/-1.0) for the PPBC. Over 3 months, scores on all genitourinary QOL measures improved by more than the minimum important difference thresholds in the pelvic yoga group (Table), and improvements in UDI-6 scores were modestly greater in the pelvic yoga than the physical conditioning group (estimated between-group difference of 5.8 (95%CI 1.0-10.6) points in favor of yoga, P=.02). However, no significant between-group differences in change in overall IIQ or PPBC scores were detected (Table). Conclusion(s): Among midlife and older women with urinary incontinence, genitourinary QOL assessed by multiple self-reported measures improved over 3 months among women assigned to a group-based pelvic yoga program, but improvements were only modestly greater than or similar to those observed with a non-specific muscle conditioning program. Findings from this multisite trial provide new evidence to support benefits of engagement in pelvic yoga among midlife and older women with genitourinary symptoms, but also suggest that women may derive benefit from other general physical-based interventions. (Table Presented).

Huang Allan, B., et al. (2021). "Neoadjuvant chemotherapy for advanced stage endometrial cancer: A systematic review." Gynecologic Oncology Reports 38: 100887.
	Objective: While primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS.; Methods: We conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with "endometrial cancer" and "neoadjuvant chemotherapy". Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies.; Results: The nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (<1 cm of residual disease) rates were similar across both treatment groups in three separate analyses, however pooled data suggest improved rates of optimal cytoreduction for NACT + ICS vs. PCS patients (81.9% vs. 51.5% respectively). Patients receiving NACT experienced significantly shorter hospital admissions and lower operative times compared to PCS counterparts.; Conclusions: NACT followed by ICS reduces perioperative morbidity while offering similar overall survival.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 The Authors.)

Huang, G., et al. (2022). "A Systematic Review of the Cost of Chronic Pelvic Pain in Women." Journal of Obstetrics and Gynaecology Canada 44(3): 286-293.e283.
	Objective: To systematically summarize the evidence on costs related to chronic pelvic pain (CPP) for women. Data sources: Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane Library) were searched for English and French articles published from 1990 to January 2021 Study selection: Of 1304 articles screened, 67 were screened in full-text form, and a total of 13 articles were included in the final analysis. Articles included involved cost studies that estimated hospital or health system costs for pelvic pain, dysmenorrhea, dyspareunia, endometriosis with pain, interstitial cystitis, or painful bladder syndrome. Data extraction and synthesis: A standardized form was created to extract study setting, design, and population; patient demographics; study duration; and reported costs of CPP components and amounts. Two independent reviewers completed the data extraction, and discrepancies were resolved through discussion with a third reviewer. Conclusion(s): Estimated health care costs ranged from US$1367 to US$7043 per woman per year. Prescription costs ranged from US$193 to US$2457 per woman per year. Indirect costs ranged from US$4216 to US$12 789 per woman per year. Combined costs ranged from US$1820 to US$20 898 per woman per year. The yearly costs of CPP varied according to country; yearly costs were estimated to be $2.8 billion, 191,680 to 246,488, and $16 970 to $20 898 per woman per year in the United Sates, Japan, and Australia, respectively. The literature suggests that CPP represents a considerable economic burden on women and health care systems internationally, with indirect costs contributing a significant portion of total costs.Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Societe des obstetriciens et gynecologues du Canada.

Huang, H., et al. (2021). "Hepatic hilar lymph node resection in cytoreductive surgery for advanced ovarian cancer: A necessity or not?" Cancer Management and Research 13: 7981-7988.
	Objective: This review aims to clarify the necessity of hepatic hilar lymph node resection on advanced ovarian cancer patients. Background(s): PARP inhibitors and surgery have significantly improved the survival of patients with ovarian cancer. However, for patients with advanced ovarian cancer, there are often extensive epigastric disseminated metastatic lesions, especially the lymph nodes in the hepatic hilar area. Because of the complicated anatomical relationship and lack of experience in this area, this is easily ignored by gynecological oncologists. Method(s): Through the retrieval and analysis of the current database, namely PubMed, Medline, Web of Science, EMBASE, Cochrane Library, and Wangfang, etc., the literature regarding this topic published before March 2021 were thoroughly investigated. Conclusion(s): For the hepatic hilar regional lymph node surgery, through careful preoperative evaluation, surgical-indication clarification, appropriate case selection, standardized surgical operations and multidisciplinary cooperation with general surgeons, the prognosis of patients is significantly improved. Postoperative complications are also safe and controllable and convincing. To conclude, the application of hilar region lymph node cytoreductive surgery for patients with advanced ovarian cancer is a feasible and preferred choice.Copyright © 2021 Huang et al.

Huang, J., et al. (2023). "Global incidence, risk factors and trends of vulvar cancer: A country-based analysis of cancer registries." International journal of cancer 153(10): 1734-1745.
	Vulvar cancer is an uncommon malignancy. Vulvar cancer alarmed the public health problem in terms of the cost of diagnostic and medical treatments and psychical health of females. Our study aims to provide a thorough analysis of the global disease burden, related risk factors and temporal incidence trends of vulvar cancer in population subgroups. Data from Global Cancer Observatory and the Cancer Incidence in Five Continents Plus were used for the vulvar cancer incidence. Age-standardized rates (ASR) were used to depict the incidence of vulvar cancer. The 10-year trend of incidence was assessed using joinpoint regression with average annual percentage change and 95% confidence intervals in various age groups, while its correlations with risk factors were investigated using linear regression. Higher ASR were found in Western Europe (2.4), Northern America (1.9), Northern Europe (1.9), Australia and New Zealand (1.8) and Eastern Africa (1.4). The associated risk factors of higher vulvar cancer incidence were gross domestic product per capita, Human Development Index, higher prevalence of smoking, alcohol drinking, unsafe sex and human immunodeficiency virus infection. The overall trend of vulvar cancer incidence was increasing. An increasing trend was found in older females while a mixed trend was observed in younger females. The disease burden of vulvar cancer follows a bimodal pattern according to its two histologic pathways, affecting women in both developed and developing regions. Smoking cessation, sex education and human papillomavirus vaccination programs should be promoted among the general population. Subsequent studies can be done to explore the reasons behind the increasing trend of vulvar cancer. (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Huang, J., et al. (2022). "Comparative Efficacy of Neuromodulation Technologies for Overactive Bladder in Adults: A Network Meta-Analysis of Randomized Controlled Trials." Neuromodulation : journal of the International Neuromodulation Society.
	OBJECTIVE: The aim of this study was to investigate the comparative efficacy of neuromodulation technologies for overactive bladder (OAB) syndrome in adults. DATA SOURCES: A computerized search was conducted of Cochrane Library, EMBASE, MEDLINE (via PubMed), Web of Science, CNKI, Wan Fang Data, and ClinicalTrials.gov up to April 21, 2022. STUDY SELECTION: The search selected clinical trials with random allocation to percutaneous tibial nerve stimulation (PTNS), transcutaneous tibial nerve stimulation (TTNS), vaginal electrical stimulation (VES), sacral neuromodulation (SNM), parasacral stimulation (PS), pudendal neuromodulation, or placebo. DATA EXTRACTION: The main outcomes were the voiding diary, OAB-related quality of life, and positive response rate. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias of each included study, and the Grading of Recommendations Assessment, Development, and Evaluation tool was used to evaluate the overall evidence quality of key outcomes. DATA SYNTHESIS: The study included 21 randomized controlled trials involving 1433 participants, and all trials were used for the meta-analysis. In the network meta-analyses, five of six neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, were related to higher efficacy than the placebo. Ranking probability showed that SNM was the most efficacious therapy for improving OAB-related quality of life, urinary episodes, and urinary frequency. For urgency incontinence episodes and the number of pads, PTNS and TTNS were the most efficacious modalities, respectively. CONCLUSION: Neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, may be effective and safe solutions for OAB syndrome in adults. Moreover, SNM is the most efficacious regimen for OAB-related quality of life, urinary episodes, and urinary frequency. PTNS and TTNS are the most efficacious modalities for reducing urgency incontinence episodes and the number of pads, respectively. Future studies should pay more attention to the quality of study design and report, patients who may benefit the most from neuromodulation, and the long-term effect, cost-effectiveness, and satisfaction of neuromodulation.

Huang, J., et al. (2023). "Effect of robotic versus laparoscopic surgery on postoperative wound infection in patients with cervical cancer: A meta-analysis." International wound journal.
	The objective of this research is to evaluate the risk of postoperative infection and other risks associated with robotic radical hysterectomy (RRH) compared with laparoscopic radical hysterectomy (LRH). Recent studies on RRH versus LRH have not been conclusive for cervical carcinoma. Our group attempted to use meta-analyses to evaluate the effects of both RRH and LRH on postoperative outcomes in order to make sure that the best operative method was used to prevent wound infections. We looked up Cochrane Library and published databases for this research and found 594 findings. Articles were screened by title and abstract and then carefully examined for inclusion and exclusion criteria. Data extraction was performed independently by two researchers. Comparison studies were used to describe the incidence of wound complications after surgery. The publication bias was assessed using Egger regression correlation analysis. There were six trials eligible for inclusion, of which 491 RRH and 807 LRH. Depending on surgery for cervical carcinoma, it is true that there is a difference in the way that surgery affects the postoperative complications. Our analysis demonstrated that the use of robotic operation can decrease the amount of blood loss during operation as compared with routine laparoscopy (MD, -77.69; 95% CI, -132.08, -23.30; p = 0.005). However, there were no statistical differences in the incidence of postoperative wound infections (OR, 0.54; 95% CI, 0.25, 1.19; p = 0.13) and intraoperative operative time (MD, 13.01; 95% CI, -41.38, 67.41; p = 0.64) among the two procedures. There was no statistically significant difference between these two groups of patients with severe postoperative complications. Unlike other research, the findings of this meta-analysis are not consistent with the findings of the present study, which suggest that robotic operations cannot lower the rate of postoperative wound infections. However, because of the limitations and the retrospective character of the trials covered, these findings should be interpreted with care and more extensive research is required. (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Huang, J.-X., et al. (2022). "Impact of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis." Frontiers in Reproductive Health 4: 1029381.
	Objective: The purpose of this study is to determine whether intracytoplasmic sperm injection (ICSI) is beneficial in patients with non-male factor infertility.; Methods: This systematic review and meta-analysis included articles from inception to May 2022. Published studies of non-male factor infertile women undergoing ICSI or in vitro fertilization (IVF) included in PubMed, Embase, web of science, Wanfang Database, and CNKI were searched by computer, without language restrictions. A random-effect model was applied to calculate the risk ratios (RRs) and their 95% confidence intervals (CIs). Letters, case reports, and review articles including meta-analyses and expert opinions were excluded. The primary endpoints were laboratory outcomes and pregnancy outcomes. The Secondary endpoints were neonatal outcomes.; Results: Six randomized controlled studies and 20 retrospective cohort studies met the inclusion criteria. In meta-analytic forest plots, compared with IVF, those who received ICSI treatment were not different in fertilization rate (RR = 0.99, 95% CI [0.90-1.09], P = 0.88), total fertilization failure rate (RR = 1.30, 95% CI [1.17-1.45], P < 0.00001), and good quality embryo rate (RR = 0.94, 95% CI [ 0.86-1.02], P = 0.15), clinical pregnancy rate (RR = 0.84, 95% CI [0.70-1.01], P = 0.06), live birth rate (RR = 0.89, 95% CI [0.77-1.03], P = 0.13), miscarriage rate (RR = 1.06, 95% CI [0.78-1.43], P = 0.71), preterm neonatal delivery rate (RR = 0.92, 95% CI [0.67-1.26], P = 0.61), and low neonatal weight rate (RR = 1.13, 95% CI [0.80-1.61], P = 0.48). However, the implantation rate of IVF was better than ICSI (RR = 0.77, 95% CI [0.64-0.93], P = 0.005). In the subgroup analysis of the live birth rate of fresh embryo transfer, IVF performed in those ≥35 years had a higher live birth rate (RR = 0.82, 95% CI [0.78-0.83], P < 0.001).; Conclusion: The findings of this study indicate that ICSI is not superior to IVF in the treatment of infertility related to non-male factors. In order to confirm this result, more high-quality clinical studies are needed.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2022 Huang, Gao, Chen, Han, Song and Sun.)

Huang, K., et al. (2023). "Efficacy and safety of different thermal ablative therapies for desmoid-type fibromatosis: a systematic review and metaanalysis." Quantitative Imaging in Medicine and Surgery 13(10): 6683-6697.
	Background: Desmoid-type fibromatosis (DF) is a locally aggressive tumor characterized by peripheral infiltration of neoplastic cells and remote metastasis disability. This systematic review examined the efficacy and safety of thermal ablative therapy for DF tumors. Method(s): A literature search was conducted using PubMed, Web of Science, Cochrane Library, and Embase from January 1, 2000, to November 12, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to guide literature selection. The inclusion criteria were the following: (I) the patients were diagnosed with aggressive fibromatosis pathologically, (II) the patients were treated by thermal ablations, and (III) a focus on treatment efficacy and safety. Meanwhile, the exclusion criteria were the following: (I) cohorts of patients with hypertrophic scar, Gardner fibroma, or nodular fasciitis; (II) conference abstracts, reviews, case reports, letters to editors, comments, or editorials; (III) number of patients <5; (IV) in vitro or animal experiments; and (V) non-English language articles. The inverse variance method with a random effects model was used to obtain the pooled data. Subgroup analyses were performed to identify treatment factors. Egger test was conducted to assess the risk of publication bias. Result(s): After literature selection, 694 DF tumors were identified in 23 studies. In terms of modality, 13 studies used cryoablation, 9 studies used high-intensity focused ultrasound (HIFU), and 1 study used microwave ablation (MWA). The pooled symptom relief rate was 90% [95% confidence interval (CI): 80-97%], with that for HIFU being 100% (95% CI: 85-100%), that for cryoablation being 87% (95% CI: 74-97%), and that MWA being 89% (95% CI). The pooled major complication rate was 3% (95% CI: 1-7%), and that for each modality was as follows: HIFU =2% (95% CI: 0-6%), cryoablation =4% (95% CI: 1-8%), MWA =11%, ultrasound =6% (95% CI: 1-13%), computed tomography (CT) =2% (95% CI: 0-7%), and magnetic resonance imaging (MRI) =3% (95% CI: 0-14%). The pooled nonperfused volume rate (NPVR) was 76% (95% CI: 71-81%), and that for each modality was as follows: HIFU =77% (95% CI: 71-85%), cryoablation =74% (95% CI: 69-79%), ultrasound =75% (95% CI: 67-83%), CT =76% (95% CI: 67-87%), and MRI =78% (95% CI: 70-87%). The pooled local control rate was 88% (95% CI: 79-94%) and that for each modality was as follows: HIFU =99% (95% CI: 96-100%), cryoablation =80% (95% CI: 68-90%), and MWA =78%. The differences in major complication rate (P=0.77) and NPVR between imaging-guided modalities (P=0.40) were not significant, nor were the differences in symptom relief rate (P=0.32) and major complication rate (P=0.61) between ablative techniques; however, the differences in local control rate (P=0.01) were significant between ablative techniques. Conclusion(s): Imaging-guided thermal ablative therapies contribute to symptom relief with a duration of more than 6 months and a low major complication rate of DF tumors.Copyright © 2023 AME Publishing Company. All rights reserved.

Huang, L., et al. (2019). "Acupuncture for patients with premature ovarian insufficiency: A systematic review protocol." Medicine 98(18): e15444.
	Background: Premature ovarian insufficiency (POI) is a difficult-to-treat gynecological disorder with complex etiologies. Although acupuncture has gained increased popularity for the management of POI, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of acupuncture for patients with POI.; Methods: The following 10 databases will be searched from the publishment to July 2019: PubMed, Embase, the Web of Science, the Cochrane Central Register of Controlled Trials, 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Digital Periodicals, Chinese Biomedical Literature Database, Chinese Scientific Journal Database database), 1 Korean medical database (KoreaMed), 1 Japanese medical database (National Institute of Informatics). The primary outcomes will be the resumption of menstruation and the serum FSH levels, and the secondary outcomes include the serum Estradiol levels, anti-Mullerian hormone levels, antral follicle count, follicular growth, endometrial thickness, and adverse events. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis or a subgroup analysis will be conducted. Risk ratio for dichotomous data and mean differences or standardized mean differences for continuous data will be calculated with 95% confidence intervals using a random effects model or a fixed effects model.; Results: This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture in treating POI.; Prospero Registration Number: CRD42019125996.

Huang, L., et al. (2020). "Adjuvant therapy of Chinese herbal medicine for the treatment of adenomyosis: A protocol for systematic review." Medicine 99(25): e20560.
	Background: Adenomyosis is benign gynecologic condition with complex etiologies. Common symptoms associated with adenomyosis (AM) include menorrhagia, dysmenorrhea, chronic pelvic pain, metrorrhagia, and dyspareunia. Although Chinese herbal medicine (CHM) has often been utilized for managing AM in clinical practice in China, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a systematic review to assess the effectiveness and safety of CHM combined with Levonorgestrel-releasing intrauterine system for AM.; Methods: The following 7 databases will be searched from the publishment to December 2019: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Digital Periodicals (WAN FANG), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP). The primary outcomes will be relief in pain and uterine bleeding. The secondary outcomes include the adverse effects, CA125 variation in peripheral blood, reduction in uterine volume, and endometrial thickness. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis will be conducted. We will use risk ratio with 95% confidence interval for dichotomous data and the mean difference for continuous data.; Results: This study will provide the latest analysis of the currently available evidence for the efficacy of the adjuvant therapy of CHM for the treatment of AM.; Registration Number: OSF (DOI 10.17605/OSF.IO/A2GHY) ETHICS AND DISSEMINATION:: No ethical issues are required. The findings will be published in a peer-reviewed scientific journal.

Huang, M. L., et al. (2023). "A systematic review and meta-analysis of CT and MRI radiomics in ovarian cancer: methodological issues and clinical utility." Insights into imaging 14(1): 117.
	OBJECTIVES: We aimed to present the state of the art of CT- and MRI-based radiomics in the context of ovarian cancer (OC), with a focus on the methodological quality of these studies and the clinical utility of these proposed radiomics models. METHODS: Original articles investigating radiomics in OC published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2002, and January 6, 2023, were extracted. The methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses were performed to compare the methodological quality, baseline information, and performance metrics. Additional meta-analyses of studies exploring differential diagnoses and prognostic prediction in patients with OC were performed separately. RESULTS: Fifty-seven studies encompassing 11,693 patients were included. The mean RQS was 30.7% (range - 4 to 22); less than 25% of studies had a high risk of bias and applicability concerns in each domain of QUADAS-2. A high RQS was significantly associated with a low QUADAS-2 risk and recent publication year. Significantly higher performance metrics were observed in studies examining differential diagnosis; 16 such studies as well as 13 exploring prognostic prediction were included in a separate meta-analysis, which revealed diagnostic odds ratios of 25.76 (95% confidence interval (CI) 13.50-49.13) and 12.55 (95% CI 8.38-18.77), respectively. CONCLUSION: Current evidence suggests that the methodological quality of OC-related radiomics studies is unsatisfactory. Radiomics analysis based on CT and MRI showed promising results in terms of differential diagnosis and prognostic prediction. CRITICAL RELEVANCE STATEMENT: Radiomics analysis has potential clinical utility; however, shortcomings persist in existing studies in terms of reproducibility. We suggest that future radiomics studies should be more standardized to better bridge the gap between concepts and clinical applications.

Huang, R., et al. (2020). "Effectiveness of peer support intervention on perinatal depression: A systematic review and meta-analysis." Journal of Affective Disorders 276: 788-796.
	Background: It has been suggested that peer support intervention may offer an alternative approach to prevent or treat perinatal depression, but little is known about its effectiveness, economics, and satisfaction in the prenatal and postpartum populations. This review summarizes available evidence on the effectiveness, economics, and satisfaction of peer support intervention on perinatal depression. Method(s): Multiple electronic databases were searched in five English databases (MEDLINE, Embase, Cochrane Library, Psyc INFO, and CINAHL) and three Chinese databases (Wang Fang, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database) from inception to April 2019. Hand searching of references was also performed. Randomized controlled trials reporting peer support intervention targeting on perinatal depression were included. The quality of evidence was assessed using the Cochrane risk of bias tool. Result(s): Ten randomized controlled trials met the inclusion criteria and were included in the final analysis. Peer support intervention reduced standardized mean depressive scores (-0.37, 95% CI -0.66 to -0.08) and reduced risk ratio (0.69, 95% CI 0.49-0.96) of depression. Limitation(s): Clinical heterogeneity was observed among the included studies in peer support intervention, suggesting the existence of potential mediators, such as intensity, frequency, or type of peer support intervention. Conclusion(s): Peer support intervention may have the potential to effectively prevent perinatal depression or reduce the harm of perinatal depression. Future studies with better design/execution and larger sample size are needed to investigate potential mediators associated with the beneficial effects of peer support intervention on perinatal depression.Copyright © 2020

Huang, R., et al. (2020). "The short- and long-term effectiveness of mother-infant psychotherapy on postpartum depression: A systematic review and meta-analysis." Journal of Affective Disorders 260: 670-679.
	Background: It has been suggested that mother-infant psychotherapy may offer an alternative approach to treating postpartum depression, but little is known about its effectiveness. This review presents a summarized effectiveness of mother-infant psychotherapy on postpartum depression. Method(s): Multiple electronic databases were searched including Pubmed, Cochrane Library, EMBase, MEDLINE, et al. Hand searching of references was also performed. Randomized controlled trials reporting on mother-infant psychotherapy targeting postpartum depression were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool. Result(s): A total of 13 randomized controlled trials met inclusion criteria and were included in the final analysis. In the short-term effect analysis, mother-infant psychotherapy reduced standardized mean depressive scores (-0.25, 95% CI -0.40, -0.09) and risk ratio (0.71, 95% CI 0.55, 0.91). In the long-term effect analysis, mother-infant psychotherapy did not improve maternal mood, mother-infant interaction and infant attachment. Limitation(s): Clinical heterogeneity was observed among included studies in mother-infant psychotherapy intervention, suggesting the existence of potential moderators such as intensity, frequency, trimester of pregnancy or type of mother-infant psychotherapy. Conclusion(s): Mother-infant psychotherapy appears to be effective for the treatment of maternal depression in the short-term. Future studies with better design/execution and larger sample size are needed to confirm the effect of mother-infant psychotherapy on short-term and to explore its effect on long-term depression.Copyright © 2019 Elsevier B.V.

Huang, S. and F. Qiu (2022). "Nursing of Vulvar Cancer Radical Operation Combined with Laparoscopic Inguinal Lymph Node Dissection [retracted]." Emergency Medicine International 2022: 8091114.
	Purpose. The application, development, and care of radical surgery combined with laparoscopic inguinal lymph node dissection for vulvar cancer. Methods. We searched the PubMed, Web of Science, the Cochrane Library, and EMBASE databases for published literature on the care of radical surgery combined with laparoscopic inguinal lymph node dissection for vulvar cancer up to June 2022. We used the following search terms and terms: "vulvar cancer,""injury,""radical vulvar cancer surgery,""laparoscopic inguinal lymph node dissection,"and "care."Results. Laparoscopic inguinal lymph node dissection has become a new surgical method for the treatment of vulvar cancer, and it effectively avoids all the problems associated with traditional surgery. In addition, radical vulvar cancer surgery and laparoscopic inguinal lymph node dissection combined with high-quality nursing interventions can promote patients' recovery and reduce the occurrence of complications, which has important clinical significance. Conclusion. This article reviews the application, development, and nursing care of radical vulvar cancer surgery combined with laparoscopic inguinal lymph node dissection.Copyright © 2022 Simei Huang and Feifei Qiu.

Huang, S., et al. (2021). "Efficacy of acupuncture for PCOS infertility: A systematic review." Chinese Journal of Evidence-Based Medicine 21(4): 431-437.
	Objective To systematically review the efficacy of acupuncture for PCOS infertility. Methods PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP and CBM databases were electronically searched to collect randomized controlled trials (RCTs) of acupuncture for PCOS infertility from inception to January 5th, 2020. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 28 RCTs involving 2 192 patients were included. The results of meta-analysis showed that compared with western medicine alone, acupuncture could increase the pregnancy rate (RR=1.80, 95%CI 1.45 to 2.23, P<0.000 01) and ovulation rate (RR=1.33, 95%CI 1.15 to 1.54, P=0.000 1), and reduce levels of LH (SMD=-0.62, 95%CI -0.96 to -0.28, P=0.000 4) and LH/FSH (SMD=-0.65, 95%CI -1.02 to -0.29, P=0.000 5). Acupuncture combined with western medicine could increase the pregnancy rate (RR=1.75, 95% CI 1.50 to 2.03, P<0.000 01) and ovulation rate (RR=1.29, 95%CI 1.18 to 1.41, P<0.000 01), decrease levels of LH (SMD=-1.09, 95%CI -1.64 to -0.53, P=0.000 1), LH/FSH (SMD=-1.30, 95%CI -2.35 to -0.25, P=0.02), and levels of T (SMD=-1.13, 95%CI -1.59 to -0.66, P<0.000 01). Conclusions Current evidence shows that acupuncture alone or combined with western medicine can significantly improve ovulation rate, pregnancy rate and reduce hormone level. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.Copyright © 2021 West China University of Medical Science. All rights reserved.

Huang, W., et al. (2022). Acupuncture Combined with Chinese Herbal Medicine for Tubal Obstructive Infertility: A Systematic Review and Meta-Analysis, Research Square.
	Background: Tubal obstruction is the leading cause of infertility. Acupuncture and Chinese herbal medicine (CHM) are widely used in treating tubal obstruction infertility (TOI), and clinical research is increasing. However, there is still controversy about its efficacy and safety. This systematic review aimed to assess the efficacy and safety of acupuncture and CHM in treating TOI. Methods: We searched eight databases to collect randomized controlled trials comparing Hydrotubation with Acupuncture combined with CHM from inception to July 31, 2022. A total of 1580 papers were collected, and the methodological quality of the included trials was assessed in line with the criteria of the Cochrane risk of the bias assessment tool. In the end, only 18 randomized clinical trials met the requirements and were included. Results: Meta-analysis showed that acupuncture and CHM was associated with a higher pregnancy rate [RR 1.74, 95% CI (1.54, 1.95), P &amp;lt; 0.00001] and a lower ectopic pregnancy rate [OR 0.61, 95 % CI (0.19, 1.92), P＜0.0001]. The success rate of tubal recanalization was significantly improved with acupuncture combined with CHM treatment[RR 1.37, 95 % CI (1.20, 1.57), P＜0.0001], and signs and symptoms were better relieved [OR 3.44, 95 % CI (2.22, 5.33), P＜0.00001]. Conclusions: This meta-analysis suggests that acupuncture and CHM can be used as complementary therapies to treat tubal obstructive infertility with better outcomes than Hydrotubation.

Huang, W., et al. (2022). "Emerging Roles of m 6 A RNA Methylation Regulators in Gynecological Cancer." Frontiers in Oncology 12: 827956.
	Gynecological cancers seriously affect the reproductive system of females; diseases include ovarian tumors, uterine tumors, endometrial cancers, cervical cancers, and vulva and vaginal tumors. At present, the diagnosis methods of gynecological cancer are insufficiently sensitive and specific, leading to failure of early disease detection. N 6 -methyladenosine (m 6 A) plays various biological functions in RNA modification and is currently studied extensively. m 6 A modification controls the fate of transcripts and regulates RNA metabolism and biological processes through the interaction of m 6 A methyltransferase ("writer") and demethylase ("erasers") and the binding protein decoding m 6 A methylation ("readers"). In the field of epigenetics, m 6 A modification is a dynamic process of reversible regulation of target RNA through its regulatory factors. It plays an important role in many diseases, especially cancer. However, its role in gynecologic cancers has not been fully investigated. Thus, we review the regulatory mechanism, biological functions, and therapeutic prospects of m 6 A RNA methylation regulators in gynecological cancers.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Huang, Kong, Li, Chen and Wang.)

Huang, W., et al. (2023). "Comparative efficacy of acupuncture-related interventions for tubal obstructive infertility: A systematic review and Bayesian meta-analysis of randomized controlled trials." Complementary Therapies in Medicine 79: 103003.
	Background: Tubal obstructive infertility (TOI) is a challenging condition affecting many women worldwide. Acupuncture and herbal medicine have emerged as potential therapeutic options for enhancing fertility outcomes in these patients. However, the evidence regarding their efficacy remains inconclusive, necessitating a comprehensive systematic review and meta-analysis. Method(s): Computer searches were conducted in PubMed, Cochrane, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Database, and China Biology Medicine (CBM) databases to retrieve relevant literature on the efficacy and safety of acupuncture and related therapies for the treatment of tubal obstructive infertility. The search period extended from the inception of the databases to December 2022. Two researchers independently screened the literature based on strict inclusion criteria, extracted relevant data, and utilized Cochrane Collaboration tools and the Jadad scale to comprehensively assess the quality of the included studies. Subsequently, pairwise meta-analysis and network meta-analysis were performed using statistical software such as StataSE and Rstudio, and graphical representations were generated to present the results. Result(s): The network meta-analysis included 1580 articles, with 23 meeting the criteria. These studies involved 2355 patients and explored 13 intervention measures. Acupuncture-related therapies outperformed control interventions in improving pregnancy rates, tubal patency rates, and overall effectiveness while demonstrating a lower incidence of adverse events. EA+CHM was identified as the most effective for pregnancy rates, MOX for tubal patency rates, and MOX+AP for overall effectiveness. The safety profile of acupuncture-related interventions was acceptable. These findings support acupuncture-related therapies as effective and safe options for tubal obstructive infertility management. Further high-quality research is needed to validate and expand upon these results. Conclusion(s): These findings offer novel treatment strategies for acupuncture-related interventions, providing practitioners with evidence-based guidance. Addressing limitations through future research is crucial, including diverse literature, emphasizing higher-quality RCTs, and exploring a broader range of interventions with long-term follow-up data. Systematic assessment of adverse events, standardized techniques, and robust ranking methods should be considered.Copyright © 2023 The Authors

Huang, Y., et al. (2022). "Feasibility and safety of performing cesarean myomectomy: a systematic review and meta-analysis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(13): 2619-2627.
	Purpose: To examine the feasibility and safety of performing cesarean myomectomy on pregnant women with myomas compared to cesarean section only.; Methods: We retrieved English articles in the PubMed, Cochrane Library, Medline and EMBASE databases from inception to April 2020. Observational studies including the comparison of patients who underwent cesarean myomectomy and cesarean section, as well as those reporting perioperative outcomes were selected. Data extraction was conducted using RevMan 5.3.; Results: Twenty-three studies comprising 8,016 women were included in the meta-analysis. Of these, 3,955 underwent cesarean myomectomy, while 4,061 underwent cesarean section only. Cesarean myomectomies were associated with a greater decline in mean hemoglobin (mean difference [MD] 0.20 g/dL, 95% confidence intervals [CI] 0.06, 0.35, p = .007), greater incidence of hemorrhage (odds ratio [OR] 1.46, 95% CI 1.06, 2.01, p = .02), greater volume of blood loss (MD 45.54 ml, 95% CI 2.68, 88.41, p = .04), higher transfusion rate (OR 1.47 95%CI 1.09, 1.99, p = .01), longer operation duration (MD 10.40 min, 95% CI 8.54, 12.25, p < .001), or longer postoperative hospitalization (MD 0.18 d, 95% CI 0.12, 0.24, p < .001), compared to those who underwent cesarean section only. There was no statistical difference in postoperative fever rates (OR 1.12, 95% CI 0.77, 1.62).; Conclusion: Hemorrhage represents a risk factor which should not be overlooked by surgeons performing cesarean myomectomy. Intramural myomas, myomas ≥7 cm in size, and multiple myomas are associated with more intraoperative hemorrhage and prolonged operation duration. We suggest that, with appropriate hemostatic techniques and when performed by experienced surgeons, cesarean myomectomy may be safe and feasible in selected patients with myomas, regardless of size and locations, except if they are located at the cornual or close to large vessels, and in the absence of uterine atony during surgery.

Huang, Y., et al. (2023). "Impact of metformin on survival in patients with ovarian cancer: a meta-analysis." Chinese Journal of Cancer Prevention and Treatment 30(20): 1242-1249.
	Objective The effect of metformin on the survival rate of ovarian cancer patients was analyzed, which provided a reference for reducing the risk of cancer and improving the survival rate of patients. Methods We searched PubMed,Em-base, and Web of Science databases as of 2022-10-25. The medical subject terms and text terms included metformin, bigua-nides,diabetic medications, ovarian, ovary, cancer, neoplasms, tumor, carcinoma, survival, mortality, prognosis and death. The data and features were extracted for each study,and 95%CI and HR values were calculated to assess the effects of metformin on overall survival (OS) and progression-free survival (PFS) in diabetic patients with ovarian cancer,and finally 10 articles were included. Results Metformin had significant benefits on the survival rate of ovarian cancer patients, HR=0. 59,95%CI:0. 49-0. 72. Subgroup analysis showed that metformin could improve OS in diabetic ovarian cancer patients, Hi? = 0. 65 , 95% CI: 0. 53 - 0. 81. However, metformin was not associated with PFS in diabetic ovarian cancer patients,HR=0. 48, 95%CI:0. 22 - 1. 05. Compared with patients without diabetic ovarian cancer,metformin was associated with OS and PFS in diabetic ovarian cancer patients,and the combined HR values were 0. 39 (95%CJ:0. 20 - 0. 76) and 0. 39 (95%CJ:0. 26 - 0. 57) , respectively. The use of metformin >720 days can improve the OS of diabetic ovarian cancer patients, Hi? = 0. 31,95%CI:0. 16 - 0. 57. Metformin was not associated with disease-specific survival in diabetic o-varian cancer patients, HR = 0. 59 , 95% CI: 0. 31 - 1. 12. Conclusion The current study has tentatively confirmed that metformin may be associated with survival benefits in patients with ovarian cancer,but more research is required for confirmation.Copyright © 2023 Chinese Journal of Cancer Prevention and Treatment, Editorial board. All rights reserved.

Huang, Y., et al. (2023). "Effect of hysterectomy on ovarian function: a systematic review and meta-analysis." Journal of Ovarian Research 16(1): 35.
	Background: Hysterectomy is one of the most frequently gynecologic surgeries performed in premenopausal women. Many premenopausal patients are unwilling to undergo hysterectomy due to the probable decreased ovarian function. The aim of this study is to determine the effect of hysterectomy on ovarian function.; Methods: A meta-analysis has been reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and the A Measurement Tool to Assess Systematic Reviews (AMSTAR) guidelines. We mainly searched the Embase, PubMed and Web of Science databases for eligible studies. The outcomes were the levels of common indicators of ovarian function, such as anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, estradiol (E2) and luteinizing hormone (LH). The evidence was synthesized using meta-analysis via fixed or random effect model according to heterogeneity. Subgroup analyses were performed to examine the potential sources of heterogeneity.; Results: The 14 included studies were conducted between 1989 and 2021, involving a total of 1,457 premenopausal women with 760 and 697 in the hysterectomy and control group, respectively. We found that hysterectomy damage ovarian function compared to the control group, with lower AMH level [Weighted mean difference (WMD) = -0.56, 95% confidence interval (95% CI): -0.72 to -0.39, P = 0.000], higher FSH levels (WMD = 2.96, 95% CI: 1.47 to 4.44, P = 0.000), lower inhibin B levels (WMD = -14.34, 95% CI: -24.69 to -3.99, P = 0.000) and higher LH levels (WMD = 4.07, 95% CI: 1.78 to 6.37, P = 0.000). In addition, E2 levels have a decreasing trend (WMD = -17.13, 95% CI: -35.10 to 0.85, P = 0.631) in the hysterectomy group but were not statistically significant.; Conclusion: Hysterectomy has a negative impact on ovarian function, especially in female patients over 40 years old. So, the older patients should closely monitor their ovarian function for early diagnosis and treatment of menopausal symptoms. (© 2023. The Author(s).)

Huang, Y. and X. Zhang (2023). "Meta-analysis of the efficacy of ω-3 polyunsaturated fatty acids when treating patients with polycystic ovary syndrome." Medicine 102(39): e35403.
	Objective: To systematically assess the efficacy of ω-3 polyunsaturated fatty acids (PUFAs) when treating polycystic ovary syndrome (PCOS).; Methods: This meta-analysis follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We searched PubMed, EMBASE, ScienceDirect, Cochrane Library, China journal full-text database, VIP full-text Database, Wanfang Database, and Chinese Biomedical Literature Data for clinical trials on ω-3 PUFAs' efficacy in treating PCOS. Two independent reviewers examined and analyzed studies, resolving inconsistencies through discussion. RevMan5.3 software performed heterogeneity-based fixed and random-effects meta-analysis. We assessed bias using the Cochrane bias risk assessment tool.; Results: Our meta-analysis included 7 clinical control studies comprising 574 samples to evaluate the impact of ω-3 PUFAs on various metabolic markers in PCOS patients. We observed a significant reduction in total cholesterol (TC) and triglyceride (TG) levels (P < .05), along with a decrease in insulin resistance as measured by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P < .05). Testosterone (T) levels were also lowered in the study group post-treatment (P < .05). However, no notable effects were found on body mass index (BMI), fasting blood sugar (FBS), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Ferriman-Gallwey (mFG) scores (P > .05). Publication bias was not detected, enhancing the robustness of our results. Our study suggests that ω-3 PUFAs could be beneficial in managing specific metabolic markers in PCOS, although the results showed marked heterogeneity.; Conclusion: In PCOS patients, PUFAs can enhance reproductive endocrine, glucose, and lipid levels. However, additional research and extended follow-up are required to confirm this.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Huang, Y., et al. (2022). "Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects." Frontiers in Immunology 13: 997808.
	Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can't restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Huang, Zhu, Liu, Hu, Li, Song, Geng, Ma, Song and Zhang.)

Huang, Z., et al. (2021). "Efficacy of tamoxifen for infertile women with thin endometrium undergoing frozen embryo transfer: A meta-analysis." Clinical and Experimental Obstetrics and Gynecology 48(4): 806-811.
	Background: This study aims to compare the effect of tamoxifen (TMX) vs. other regimens on endometrial thickness (EMT), clinical pregnancy, implantation, miscarriage, and live birth rates in women with thin endometrium undergoing frozen-thawed embryo transfer (FET). Method(s): We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and CINAHL from inception to November 2020 and cross-checked the references of relevant articles. We included randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) to compare TMX with other regimens for endometrium preparation in women with thin endometrium undergoing FET. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and odds ratios (OR) with 95% CI for binary variables (i.e., clinical pregnancy rate, implantation rate, and first trimester miscarriage rate). Result(s): An RCT and three controlled trials (2 beforeafter and 1 retrospective controlled trials) were included in the final review. One study including 154 women and comparing TMX-FET with natural cycle (NC)-FET showed a significant increase in EMT in the TMX cycle (7.87 +/- 1.48 mm vs. 6.11 +/- 0.98 mm, P < 0.05). Three studies compared the EMT in the TMX and the hormone replacement treatment (HRT) cycles. The pooled analysis showed beneficial effect of TMX on EMT (WMD = 2.06, 95% CI = 1.86-2.27, P < 0.00001). An RCT and a retrospective controlled trial compared TMX and ovulation induction (OI) with Letrozole/human menopause gonadotropin (hMG) for endometrium preparation in women with thin endometrium undergoing FET. No significant difference in clinical pregnancy rates (OR = 1.03, 95% CI = 0.71-1.51), implantation rate (OR = 1.03, 95% CI = 0.76-1.38), or miscarriage rate (OR = 0.91, 95% CI = 0.40-2.06) was observed. No significant difference in EMT was found between TMX and OI with Letrozole/hMG in the included studies. Conclusion(s): In women with thin endometrium undergoing FET, the use of TMX may result in improved EMT than other regimens. At present, evidence supporting the preferred use of TMX over other regimens as clinical pregnancy rate, implantation rate, or the first trimester miscarriage rate is insufficient.Copyright © 2021 The Author(s).

Huaqian, W., et al. (2022). "network meta-analysis of three different surgical strategies for cesarean scar defect."
	
Huddleston Heather, G. and A. Dokras (2022). "Diagnosis and Treatment of Polycystic Ovary Syndrome." JAMA 327(3): 274-275.
	
Huepenbecker, S., et al. (2022). "Cost-utility analysis of management strategies after frontline treatment of women with epithelial ovarian cancer (339)." Gynecologic Oncology 166(Supplement 1): S174-S175.
	Objectives: Performed a cost-utility analysis comparing maintenance therapies for advanced epithelial ovarian cancer to surveillance based on genetic mutation. Method(s): We developed Markov models of post-frontline treatment disease course until death for women diagnosed with stage III-IV epithelial ovarian cancer to compare niraparib, olaparib, bevacizumab, and olaparib+bevacizumab with active surveillance. Four subgroups were analyzed: (1) all-comers, (2) BRCA, (3) non-BRCA homologous recombination deficiency (HRD), and (4) homologous recombination proficient (HR proficient). Transition probabilities for progression-free survival and adverse events were derived from randomized controlled trials, for all-cause mortality from US life tables, and for disease-specific mortality after recurrence from SEER. Utilities for maintenance treatment, grade 3-4 adverse events, disease-free off treatment, recurrence, and death were derived from ovarian cancer-specific time trade-off studies. Costs of treatment, adverse events, recurrence, and death were obtained from Centers for Medicare & Medicaid Services (CMS) fee schedules and published studies. Analysis was conducted from CMS's perspective. We considered a 3-month cycle length, a lifetime time horizon and applied a 3% annual discount rate. The primary outcome of interest was the incremental cost-effectiveness ratio (ICER), defined as the ratio of incremental cost to incremental quality-adjusted life-year (QALY). Uncertainty was evaluated using deterministic and probabilistic sensitivity analyses and represented by cost-effectiveness at willingness-to-pay (WTP) thresholds up to $200K/QALY. Result(s): For all-comers, surveillance and olaparib+bevacizumab were undominated (more effective and less costly), and the ICER of olaparib+bevacizumab in reference to surveillance was $182,823/ QALY. The probability of cost-effectiveness of olaparib+bevacizumab at a WTP threshold of $100K/QALY was 20%. For BRCA patients, surveillance and olaparib were nominated, and the ICER of olaparib was $49,896/QALY. The probability of olaparib being cost-effective at a WTP threshold of $100K/QALY was 71%. For non-BRCA HRD patients, surveillance and olaparib+bevacizumab were both undominated, and the ICER of olaparib+bevacizumab was $98,685/QALY. At a WTP threshold of $100,000/QALY, olaparib+bevacizumab had a higher probability of being cost-effective (48%) than niraparib (6%) or bevacizumab alone (4%). For HR proficient patients, surveillance was undominated and had the highest probability of being cost-effective at all WTP thresholds. Conclusion(s): Compared to active surveillance, olaparib+bevacizumab was the most cost-effective maintenance strategy for all-comers and non-BRCA HRD patients. At the same time, olaparib was most costeffective for women with BRCA mutations. The likelihood of any maintenance therapy being cost-effective for women with HR proficient disease was low.Copyright © 2022 Elsevier Inc.

Huepenbecker, S. P., et al. (2024). "Longitudinal perioperative patient-reported outcomes in open compared with minimally invasive hysterectomy." American Journal of Obstetrics and Gynecology 230(2): 241.e241-241.e218.
	Background: There are few prospective studies in the gynecologic surgical literature that compared patient-reported outcomes between open and minimally invasive hysterectomies within enhanced recovery after surgery pathways. Objective(s): This study aimed to compare prospectively collected perioperative patient-reported symptom burden and interference measures in open compared with minimally invasive hysterectomy cohorts within enhanced recovery after surgery pathways. Study Design: We compared patient-reported symptom burden and functional interference in 646 patients who underwent a hysterectomy (254 underwent open surgery and 392 underwent minimally invasive surgery) for benign and malignant indications under enhanced recovery after surgery protocols. Outcomes were prospectively measured using the validated MD Anderson Symptom Inventory, which was administered perioperatively up to 8 weeks after surgery. Cohorts were compared using Fisher exact and chi-squared tests, adjusted longitudinal generalized linear mixed modeling, and Kaplan Meier curves to model return to no or mild symptoms. Result(s): The open cohort had significantly worse preoperative physical functional interference (P=.001). At the time of hospital discharge postoperatively, the open cohort reported significantly higher mean symptom severity scores and more moderate or severe scores for overall (P<.001) and abdominal pain (P<.001), fatigue (P=.001), lack of appetite (P<.001), bloating (P=.041), and constipation (P<.001) when compared with the minimally invasive cohort. The open cohort also had significantly higher interference in physical functioning (score 5.0 vs 2.7; P<.001) than the minimally invasive cohort at the time of discharge with no differences in affective interference between the 2 groups. In mixed modeling analysis of the first 7 postoperative days, both cohorts reported improved symptom burden and functional interference over time with generally slower recovery in the open cohort. From 1 to 8 postoperative weeks, the open cohort had worse mean scores for all evaluated symptoms and interference measures except for pain with urination, although scores indicated mild symptomatic burden and interference in both cohorts. The time to return to no or mild symptoms was significantly longer in the open cohort for overall pain (14 vs 4 days; P<.001), fatigue (8 vs 4 days; P<.001), disturbed sleep (2 vs 2 days; P<.001), and appetite (1.5 vs 1 days; P<.001) but was significantly longer in the minimally invasive cohort for abdominal pain (42 vs 28 days; P<.001) and bloating (42 vs 8 days; P<.001). The median time to return to no or mild functional interference was longer in the open than in the minimally invasive hysterectomy cohort for physical functioning (36 vs 32 days; P<.001) with no difference in compositive affective functioning (5 vs 5 days; P=.07) between the groups. Conclusion(s): Open hysterectomy was associated with increased symptom burden in the immediate postoperative period and longer time to return to no or mild symptom burden and interference with physical functioning. However, all patient-reported measures improved within days to weeks of both open and minimally invasive surgery and differences were not always clinically significant.Copyright © 2023 Elsevier Inc.

Huerga, L., et al. (2023). "Management of uterine fibroids: Approach to medical treatment." Medicina clinica 161 Suppl 1: S15-S21.
	
Hughes, O., et al. (2023). "Living With Physical Health Conditions: A Systematic Review of Mindfulness-Based Interventions for Children, Adolescents, and Their Parents." Journal of pediatric psychology 48(4): 396-413.
	Objectives: This systematic review aimed to identify and appraise studies investigating the efficacy of mindfulness-based interventions (MBIs) for improving depression, anxiety and parental stress in families affected by childhood physical illnesses, as well as feasibility and acceptability.; Methods: Embase, PsycINFO, Scopus, Medline, and PubMed were searched between February 2 and 17, 2021, and updated on August 5, 2022. Studies investigating MBIs with children and adolescents (<18 years) with physical health conditions were included, and results are presented with narrative synthesis.; Results: Eighteen studies met eligibility criteria. Studies included children and adolescents with chronic pain, headaches, cancer, heart conditions, esophageal atresia, inflammatory bowel disease, and polycystic ovary syndrome. Most studies reported mindfulness was feasible and acceptable, although findings for different health conditions were mixed. Some studies encountered difficulties with attrition, resulting in findings being underpowered.; Conclusions: MBIs show promise for improving anxiety and depression in children with physical health conditions, but there is limited support for reducing stress in the family unit. A potential direction for future research might be the inclusion of parents. However, because of the heterogeneity of studies included in this review, findings must be cautiously interpreted. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology.)

Huijs, D. P. C., et al. (2024). "A 52-mg levonorgestrel-releasing intrauterine system vs bipolar radiofrequency nonresectoscopic endometrial ablation in women with heavy menstrual bleeding: long-term follow-up of a multicenter randomized controlled trial." American Journal of Obstetrics and Gynecology.
	Background: The symptom of heavy menstrual bleeding has a substantial impact on professional, physical, and social functioning. In 2021, results from a randomized controlled trial comparing a 52-mg levonorgestrel-releasing intrauterine system and radiofrequency nonresectoscopic endometrial ablation as treatments for women with heavy menstrual bleeding were published. Both treatment strategies were equally effective in treating heavy menstrual bleeding during 2-year follow-up. However, long-term results are also relevant for both patients and healthcare providers. Objective(s): This study aimed to assess long-term differences in reintervention risk and menstrual blood loss in women with the symptom of heavy menstrual bleeding treated according to a strategy starting with a 52-mg levonorgestrel-releasing intrauterine system or radiofrequency nonresectoscopic endometrial ablation. Study Design: This study was a long-term follow-up study of a multicenter randomized controlled trial (MIRA trial), in which women were allocated to either a 52-mg levonorgestrel-releasing intrauterine device (n=132) or radiofrequency nonresectoscopic endometrial ablation (n=138). Women from the original trial were contacted to fill out 6 questionnaires. The primary outcome was the reintervention rate after allocated treatment. Secondary outcomes included surgical reintervention rate, menstrual bleeding measured by the Pictorial Blood Loss Assessment Chart, (disease-specific) quality of life, sexual function, and patient satisfaction. Result(s): From the 270 women who were randomized in the original trial, 196 (52-mg levonorgestrel-releasing intrauterine system group: n=94; radiofrequency nonresectoscopic endometrial ablation group: n=102) participated in this long-term follow-up study. Mean follow-up duration was 7.4 years (range, 6-9 years). The cumulative reintervention rate (including both medical and surgical reinterventions) was 40.0% (34/85) in the 52-mg levonorgestrel-releasing intrauterine system group and 28.7% (27/94) in the radiofrequency nonresectoscopic endometrial ablation group (relative risk, 1.39; 95% confidence interval, 0.92-2.10). The cumulative rate of surgical reinterventions only was significantly higher among patients with a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system compared with radiofrequency nonresectoscopic endometrial ablation (35.3% [30/85] vs 19.1% [18/94]; relative risk, 1.84; 95% confidence interval, 1.11-3.10). However, the hysterectomy rate was similar (11.8% [10/94] in the 52-mg levonorgestrel-releasing intrauterine system group and 18.1% [17/102] in the radiofrequency nonresectoscopic endometrial ablation group; relative risk, 0.65; 95% confidence interval, 0.32-1.34). Most reinterventions occurred during the first 24 months of follow-up. A total of 171 Pictorial Blood Loss Assessment Chart scores showed a median bleeding score of 0.0. No clinically relevant differences were found regarding quality of life, sexual function, and patient satisfaction. Conclusion(s): The overall risk of reintervention after long-term follow-up was not different between women treated according to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system and those treated using a strategy starting with radiofrequency nonresectoscopic endometrial ablation. However, women allocated to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system had a higher risk of surgical reintervention, which was driven by an increase in subsequent endometrial ablation. Both treatment strategies were effective in lowering menstrual blood loss over the long term. The results of this long-term follow-up study can support physicians in optimizing the counseling of women with heavy menstrual bleeding, thus promoting informed decision-making regarding choice of treatment.Copyright © 2024 The Author(s)

Huijs, E. and A. Nap (2020). "The effects of nutrients on symptoms in women with endometriosis: a systematic review." Reproductive Biomedicine Online 41(2): 317-328.
	The success rate of medical and surgical treatment for endometriosis is limited. Empowering patients suffering from endometriosis by giving them opportunities to positively influence their symptoms could result in increased quality of life. Changing diet is one of these self-management activities, but current endometriosis diets are mostly based on limited evidence. In order to gain more insight into the role of nutrients on symptoms in women with endometriosis a systematic review was carried out in which the effect of a nutrient or diet on endometriosis-related symptoms was investigated. PubMed and the Cochrane Database of Systematic Reviews were searched for relevant articles up to 1 March 2019. Search terms included endometriosis, diet, and 26 possible nutrients were identified after assessing available endometriosis diets in the literature and on the internet. Twelve studies were included. Study quality, including risk of bias, was assessed using GRADE criteria and all were of low to very low quality. Intake of additional fatty acids, antioxidants and a combination of vitamins and minerals may have a positive effect on endometriosis-associated symptoms. Future studies are necessary to gain evidence about which food products are effective and in which amounts. (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Huizinga, F., et al. (2021). "Home-based Physical Activity to Alleviate Fatigue in Cancer Survivors: A Systematic Review and Meta-analysis." Medicine and Science in Sports and Exercise 53(12): 2661-2674.
	Purpose: Physical activity (PA) affects fatigue and mental health in cancer survivors favorably, but participation in PA interventions tends to be low. More participants may be reached by home-based PA owing to greater accessibility and self-monitoring. This systematic review therefore evaluated the effects of home-based PA of low to moderate intensity on symptoms of fatigue, depression, and anxiety among cancer survivors.; Methods: PubMed, CINAHL, PsycINFO, and Web of Science were systematically searched for randomized controlled trials. We included investigations of home-based PA interventions in adults treated curatively for cancer and evaluating fatigue, depression, or anxiety as outcomes. We performed a random-effect meta-analysis for the effects of PA interventions on fatigue in the short and long terms. Subgroup analyses were performed for the frequency of counseling. Standardized mean differences (SMD) and 95% confidence intervals are reported.; Results: Eleven articles comprising 1066 participants were included: 77% had a history of breast cancer; 14%, ovarian cancer; 4%, colorectal cancer; 4%, prostate cancer; and 1%, "other" cancer (not specified). Concerning the outcomes, nine articles reported on fatigue and two reported on depression or anxiety. Meta-analyses showed a significant effect of home-based PA on fatigue immediately after the intervention (SMD = 0.22 [0.06-0.37]), at 3 months' follow-up (SMD = 0.27 [0.04-0.51]), and at 6-9 months' follow-up (SMD = 0.31 [0.08-0.55]). PA interventions that used frequent counseling were associated with larger improvements in fatigue than those using no or infrequent counseling.; Conclusions: Home-based PA interventions can reduce fatigue among adult cancer survivors for up to 9 months, and frequent counseling may improve the benefits of these interventions. (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Hulkkonen, P., et al. (2021). "The efficacy of probiotics and/or n-3 long-chain polyunsaturated fatty acids intervention on maternal prenatal and postnatal depressive and anxiety symptoms among overweight and obese women." Journal of Affective Disorders 289: 21-30.
	BACKGROUND: Maternal depression and anxiety may endanger well-being of both mother and child. We investigated the efficacy of probiotics and/or fish oil (FO) in modifying pre- and postnatal depressive and anxiety symptoms. Symptom trajectories were identified and the influence of lifestyle factors on symptoms was evaluated. METHODS: Overweight women (n = 439) were randomized to intervention groups (probiotics+FO, probiotics+placebo, FO+placebo, placebo+placebo) from early pregnancy until six months postpartum, and assessed for depressive and anxiety symptoms with Edinburgh Postnatal Depression Scale (EPDS) and Anxiety subscale of Symptoms Checklist (SCL-90) at early and late pregnancy and three, six and 12 months postpartum. Latent growth mixture modeling was used to model the symptom courses. Dietary quality and physical activity were assessed with validated indices. RESULTS: Symptom scores were generally low. Statistically significant intervention effect was seen during pregnancy (p = 0.017): EPDS scores increased (by 1.11 points) in the FO+probiotics group and decreased (by 0.85 points) in the FO+placebo group. At 12 months postpartum, FO+placebo group had lower EPDS scores compared to probiotics+placebo group (p = 0.039). No differences in SCL scores were seen in response to the intervention. Irrespective of the intervention, three depressive and two anxiety symptoms trajectories were identified. Dietary quality correlated negatively with depressive symptoms in early pregnancy and six months postpartum and with anxiety symptoms in early pregnancy. Perinatal events including mother-reported colic were related to symptoms. LIMITATIONS: Secondary outcomes of the primary trial. CONCLUSIONS: Intervention had a modest impact on depressive symptoms. Diet and obstetric events were associated with depressive and anxiety symptoms.

Hull, L., et al. (2023). "Evaluation of 28-day estradiol and progesterone vaginal rings in a phase 1 clinical pharmacokinetic study." Menopause (New York, N.Y.) 30(4): 427-436.
	Objective: The aim of this work is to develop a combination of 17β-estradiol (E2) and progesterone (P4) in a single-dose intravaginal ring (IVR) for the treatment of vasomotor symptoms (VMS) and genitourinary syndrome of menopause while providing endometrial protection. The objective of this study was to evaluate DARE-HRT1, a 28-day IVR that continuously delivers E2 and P4, in a phase 1 clinical trial to assess its pharmacokinetics.; Methods: This was an open-label, three-arm (group) study. Thirty-two (32) healthy postmenopausal women were recruited at two Australian sites. The average age was 57.2 years (47-69 y). The first arm received one ring for 28 days designed to release E2 at a rate of 80 μg/d and P4 at 4 mg/d (80/4 IVR); the second arm received a ring releasing E2 at 160 μg/d and P4 at 8 mg/d (160/8 IVR). The third arm received oral Estrofem (1 mg E2) and Prometrium (100 mg P4) both daily for 29 days. Blood samples were taken predose then intensively over the first day (day 1) and periodically thereafter over the remaining 27 days. After removal of the rings on the morning of day 29, intensive samples were collected. Similar procedures were conducted with women enrolled in the oral group. The plasma samples were analyzed for E2, estrone (E1), and P4 using validated bioanalytical methods.; Results: The baseline-adjusted steady-state plasma levels of E2 and P4 from 80/4 IVR were 20.4 ± 17.1 pg/mL and 1.32 ± 0.19 ng/mL (n = 10), respectively. The baseline-adjusted steady-state plasma levels of E2 and P4 from 160/8 IVR were 30.9 ± 8.7 pg/mL and 2.08 ± 0.50 ng/mL (n = 10), respectively. The baseline-adjusted average plasma concentrations of E2 and P4 at day 29 of the oral group were 35.4 ± 11.2 pg/mL and 0.79 ± 0.72 ng/mL (n = 11), respectively. The baseline-adjusted steady state of E1 from the 80/4 IVR and the 160/8 IVR were 22.1 ± 16.6 pg/mL (n = 10) and 25.2 ± 12.3 pg/mL (n = 10), respectively. The baseline-adjusted concentration of E1 in the oral arm was 209 ± 67.7 ng/mL (n = 11). The IVR were well tolerated, and no serious adverse events were reported.; Conclusions: The 80/4 IVR and 160/8 IVR gave similar steady-state concentrations of E2 as seen with drug products approved by the US Food and Drug Administration for treatment of VMS and genitourinary symptoms of menopause. The E2 concentrations of this study support the potential of DARE-HRT1, a promising new option for hormone therapy for treatment of VMS and vaginal symptoms associated with menopause.; Competing Interests: Financial disclosure/conflicts of interest: David R. Friend has stock options in Daré Bioscience; Nadene Zak owns stock in Daré Bioscience. The other authors have nothing to disclose. (Copyright © 2023 by The North American Menopause Society.)

Hull, M. L., et al. (2023). "Safety and acceptability of intravaginal rings releasing estradiol and progesterone." Climacteric : the journal of the International Menopause Society 26(5): 465-471.
	Objective: This study aimed to evaluate the safety and acceptability of two fixed-dose 28-day vaginal ring formulations of 17β-estradiol (E2) and progesterone (P4) to treat vasomotor symptoms (VMS) and the genitourinary syndrome of menopause.; Design: DARE HRT1-001 was the first-in-woman study of 28-day exposure to two 28-day intravaginal rings (IVRs) designed to release 80 µg/day E2 + 4 mg/day P4 (IVR1) or 160 µg/day E2 + 8 mg/day P4 (IVR2) compared with oral E2 1 mg/day + oral P4 100 mg/day. To assess safety, participants completed a daily diary to record treatment emergent adverse events (TEAEs). To determine acceptability, at the end of treatment IVR users completed a questionnaire assessing tolerability and usability.; Results: Enrolled women ( n = 34) were randomized to use IVR1 ( n = 10), IVR2 ( n = 12) or oral ( n = 12). Thirty-one participants (IVR1 = 10, IVR2 = 10, oral = 11) completed the study. The TEAE profile of those in the IVR groups were similar to the referent oral regimen. TEAEs related to the study product were more common with IVR2 use. Endometrial biopsies were not performed unless endometrial thickness was >4 mm or for clinically significant postmenopausal bleeding. One IVR1 participant had an endometrial stripe increase from 4 mm at screening to 8 mm at the end of treatment. The biopsy indicated no evidence of plasma cells or endometritis and no evidence of atypia, hyperplasia or malignancy. Two other endometrial biopsies were performed for postmenopausal bleeding with similar findings. There were no clinically meaningful laboratory or vital sign abnormalities or trends identified in observed values or changes from baseline. Pelvic speculum examination identified no clinically significant abnormalities in any participant at any visit. Tolerability and usability data demonstrated that both IVRs were generally highly acceptable.; Conclusions: Both IVR1 and IVR2 were safe and well tolerated in healthy postmenopausal women. TEAE profiles were comparable to the referent oral regimen.

Hull University, o. (2024). Semaglutide vs Metformin in Polycystic Ovary Syndrome (PCOS).
	No Results Available Drug: Metformin|Drug: Semaglutide Injectable Product Weight loss (kg)|Fat mass|Free androgen index (FAI)|Blood pressure|Pulse rate|Glucose tolerance Female Phase 2|Phase 3 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment R2603 December 30, 2025

Hulshoff Cecile, C., et al. (2023). "The effectiveness of transabdominal cerclage placement via laparoscopy or laparotomy: a systematic review and meta-analysis." American Journal of Obstetrics & Gynecology MFM 5(1): 100757.
	Objective: Failure or technical impossibility to place a prophylactic transvaginal cerclage in women with cervical insufficiency justifies the need for an abdominal cerclage. In this systematic review and meta-analysis, we studied the obstetrical and surgical outcomes of laparoscopic and open laparotomy abdominal cerclage approaches performed before (interval) or during pregnancy.; Data Sources: We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for studies on laparoscopic and open laparotomy abdominal cerclage placement in February 2022.; Study Eligibility Criteria: All studies on laparoscopic or open laparotomy placement of an abdominal cerclage with at least 2 patients that reported on our primary outcomes were included.; Methods: All included studies were assessed for quality and risk of bias with an adjusted Quality in Prognosis Study tool. Random effects meta-analyses were performed for the primary outcomes, namely fetal survival and gestational age at delivery.; Results: Our search yielded 83 studies with a total of 3398 patients; 1869 of those underwent laparoscopic cerclage placement and 1529 underwent open laparotomy placements. No studies directly compared the 2 cerclage approaches. The survival (overall, 91.2%) and gestational age at delivery (overall, 36.6 weeks) were not statistically different between the approaches. For the procedure during pregnancy, the laparoscopic group showed significantly less blood loss >400 mL (0% vs 3%), a slightly lower procedure-related fetal loss (0% vs 1%), a shorter hospital stay but a longer operation duration than the open laparotomy group. For the interval cerclages, the laparoscopic group showed significantly fewer wound infections (0% vs 3%) and a shorter hospital stay than the open laparotomy group, but showed comparable offspring preterm birth and survival rates.; Conclusion: Based on indirect comparisons, the laparoscopic and open laparotomy abdominal cerclage placements at interval or during pregnancy produced similar outcomes in terms of survival and gestational age at delivery. There are some small differences in perioperative care, surgical complications, interventions, and complications during pregnancy. This implies that both methods of abdominal cerclage placement have high success rates and thus we cannot conclude that one of the methods is superior for the placement of an abdominal cerclage. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Humaidan, P., et al. (2023). "Local intraendometrial estrogen biosynthesis leading to progesterone resistance impacts implantation in adenomyosis and endometriosis." Fertility and Sterility 120(4): 927.
	
Human Development Research, F., et al. (2022). Thinking Healthy Program-Technology Assisted (THP-TA).
	Background: The Thinking Healthy Program (THP) is an evidence based task-shifted low intensity psychosocial intervention, recommended by the World Health Organization for the treatment of perinatal depression. The investigators developed a technology-assisted version of Thinking Healthy Program (THP-TA) which allows peers to deliver the THP, while ensuring minimal resources for training of delivery agents and ensuring adequate fidelity. Method: This is a non-inferiority, pragmatic cluster randomized controlled trial designed to test the primary hypothesis that technology assisted delivery of THP is not worse than THP intervention delivered by community health workers, in increasing perinatal depression remission rates at 3 months postnatal. In addition, this study will also test the effectiveness of the THP-TA in improving recovery from perinatal depression at 6 months postpartum, quality of life and social support. This study also aims to evaluate the cost-effectiveness of the THP-TA Primary Purpose : Treatment Allocation : Randomized Interventional Model : Parallel Assignment Masking : Double (InvestigatorOutcomes Assessor)

Humeniuk, E., et al. (2023). "Supporting the treatment of infertility using psychological methods." Annals of agricultural and environmental medicine : AAEM 30(4): 581-586.
	INTRODUCTION AND OBJECTIVE: The aim of the study was to review the current state of knowledge regarding the treatment of emotional consequences of infertility using psychosocial interventions and their effectiveness. REVIEW METHODS: The review was based on data obtained from scientific articles published in the Pub Med, Science Direct, the Cochrane Database of Systematic Reviews, Embase, Scopus, Ovid MEDLINE, Ovid EMbase, and The Cochrane Library between 1997-2022. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Assistance offered to persons afflicted by the problem of infertility may take various forms, depending not only on the needs of those interested and the stage of treatment, but also on the capabilities of the staff (type and level of education). Commonly available, well-developed and researched methods of therapy are most frequently applied, often expanded by such elements as education concerning fertility and life style, and information about diagnosis and treatment. Modified methods of psychological intervention specially adjusted to persons struggling with infertility are also used. The indicators of the effectiveness of these methods are: reduction of stress, better coping with difficulties, decrease in the rates of psychological disorders, as well as an improvement of sperm parameters in men, and an increase in pregnancy and live birth rates. SUMMARY: The most frequently recommended methods of psychosocial intervention are these based on cognitive behavioural therapy and variants of stress reduction techniques. It is recommended that patients with infertility are provided with psychological care throughout the treatment period, and that the medical staff is equipped with standardized methods of assessing their mental state.

Hunt, S. and B. Vollenhoven (2023). "Pelvic inflammatory disease and infertility." Australian journal of general practice 52(4): 215-218.
	Background: Pelvic inflammatory disease (PID) is a major cause of morbidity and reproductive difficulty in women of childbearing age.; Objective: This article outlines the pathogenesis, clinical evaluation and management of PID with a focus on the management of long-term fertility-related sequelae.; Discussion: The clinical presentation of PID can be variable and clinicians need to have a low threshold for suspecting the diagnosis. Despite a good clinical response to antimicrobials, the risk of long-term complications is high. Therefore, a history of PID would warrant early review in couples planning conception for further evaluation and discussion of the various modalities available for treatment if spontaneous conception does not occur.

Hunte Sherisse, O., et al. (2022). "Volumetric modulated arc therapy (VMAT): a review of clinical outcomes-what is the clinical evidence for the most effective implementation?" The British journal of radiology 95(1136): 20201289.
	Modern conformal radiation therapy using techniques such as modulation, image guidance and motion management have changed the face of radiotherapy today offering superior conformity, efficiency, and reproducibility to clinics worldwide. This review assesses the impact of these advanced radiotherapy techniques on patient toxicity and survival rates reported from January 2017 to September 2020. The main aims are to establish if dosimetric and efficiency gains correlate with improved survival and reduced toxicities and to answer the question 'What is the clinical evidence for the most effective implementation of VMAT?'. Compared with 3DCRT, improvements have been reported with VMAT in prostate, locally advanced cervical carcinoma and various head and neck applications, leading to the shift in technology to VMAT. Other sites such as thoracic neoplasms and nasopharyngeal carcinomas have observed some improvement with VMAT although not in line with improved dosimetric measures, and the burden of toxicity and the incidence of cancer related deaths remain high, signaling the need to further mitigate toxicity and increase survival. As technological advancement continues, large randomised long-term clinical trials are required to determine the way-forward and offer site-specific recommendations. These studies are usually expensive and time consuming, therefore utilising pooled real-world data in a prospective nature can be an alternative solution to comprehensively assess the efficacy of modern radiotherapy techniques.

Hurtado-Roca, Y., et al. (2020). "Efficacy and safety of cryotherapy, cold cone or thermocoagulation compared to LEEP as a therapy for cervical intraepithelial neoplasia: Systematic review." Revista de saude publica 54: 27.
	Objectives: To determine the efficacy and safety of the use of cryotherapy, cold knife or thermocoagulation compared to Loop Electrosurgical Excision Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia.; Methods: Systematic review with meta-analysis of randomized controlled trials in women with cervical intraepithelial neoplasia undergoing treatment with cryotherapy, cold knife, or thermo-coagulation compared with LEEP, to estimate its efficacy and safety. The search was conducted on MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus, until September 2018.; Results: The total of 72 studies were identified, of which only 8 studies met the inclusion criteria. The treatment of CIN with cold knife decreases the risk of residual disease compared with LEEP (RR, 0.54, 95%CI, 0.30-0.96, p = 0.04). The management of premalignant lesions with cryotherapy, compared with LEEP, increases the risk of disease recurrence by 86% (RR, 1.86, 95%CI, 1.16-2.97, p = 0.01), increases the risk of infections (RR, 1.17, 95%CI, 1.08-1.28, p < 0.001) and reduces the risk of minor bleeding by 51% (RR, 0.49, 95%CI) %, 0.40-0.59, p ≤ 0.001).; Conclusions: The treatment of premalignant lesions of cervical cancer with cold knife reduces the risk of residual disease. Nevertheless, cryotherapy reduces the risk of minor bleeding in the 24 hours after treatment and increases the risk of recurrence of disease and infections.

Husain, N., et al. (2023). "Exploratory RCT of a group psychological intervention for postnatal depression in British mothers of South Asian origin - ROSHNI-D." Acta psychologica 238: 103974.
	BACKGROUND: Postnatal depression (PND) is a global public health problem. There is a high prevalence of PND amongst ethnic minority women and major ethnic inequalities in mental health care in the U.K. Language and cultural barriers pose a significant challenge for access to timely treatment and interventions for British South Asian (BSA) women with PND. METHOD(S): The study, carried out in Manchester and Lancashire, England, was a two-arm single-blind exploratory randomised controlled trial. BSA women (N = 83) having a baby <12 months were randomised either to the group receiving the culturally adapted Positive Health Programme (PHP) (n = 42) or to the group receiving treatment as usual (TAU) (n = 41). Follow-up assessments were at 3 months (end of intervention) and 6 months after randomisation. RESULT(S): Using an intention to treat analysis, there was no significant difference between PHP intervention and TAU groups in depression measured using Hamilton Depression Rating Scale both at 3 and 6 months follow up. Using modified intention to treat analysis, women who attended four or more sessions showed significant reduction in depression in the PHP group compared to the TAU group and the greater number of sessions attended was associated with greater reductions in depression scores. LIMITATIONS: The sample was relatively small and the study was conducted in one geographical area in Northwest England; hence, these results may not be generalizable to other regions and populations. CONCLUSION(S): The recruitment and trial retention figures highlighted the ability of the research team to engage with BSA women, having implications in planning services for this group. TRIAL REGISTRATION: Clinicaltrials.govNCT01838889.Copyright © 2023 Lancashire and South Cumbria NHS Foundation Trust. Published by Elsevier B.V. All rights reserved.

Huss, A., et al. (2023). "Prognostic factors and survival of patients with uterine sarcoma: a German unicenter analysis." Archives of Gynecology and Obstetrics 307(3): 927-935.
	Purpose: Uterine sarcoma (US) as a histologically heterogeneous group of tumors is rare and associated with poor prognosis. Prognostic factors based on systematic data collection need to be identified to optimize patients' treatment.; Methods: This unicenter, retrospective cohort study includes 57 patients treated at the University Hospital Freiburg, Germany between 1999 and 2017. Progression-free survival (PFS) and overall survival (OS) were calculated and visualized in Kaplan-Meier curves. Prognostic factors were identified using log-rank test and Cox regression.; Results: 44 Leiomyosarcoma (LMS), 7 low-grade endometrial stromal sarcoma (LG-ESS), 4 high-grade ESS and 2 undifferentiated US patients were identified. The median age at time of diagnosis was 51.0 years (range 18-83). The median follow-up time was 35 months. PFS for the total cohort was 14.0 (95%-Confidence-Interval (CI) 9.7-18.3) and OS 36.0 months (95%-CI 22.1-49.9). Tumor pathology was prognostically significant for OS with LG-ESS being the most favorable (mean OS 150.3 months). In the multivariate analysis, patients over 52 years showed a four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-CI 1.5-12.9). Progesterone receptor negativity was associated with a two times higher risk for death (HR 2.8; 95%-CI 1.0-7.5). For LMS patients age ≥ 52 years (p = 0.04), clear surgical margins (p = 0.01), FIGO stage (p = 0.01) and no application of chemotherapy (p = 0.02) were statistically significant factors for OS.; Conclusion: Tumor histology, age at time of diagnosis and progesterone receptor status were prognostic factors for US. Unfavorable OS in LMS patients was associated with advanced FIGO stage, suboptimal cytoreduction and application of chemotherapy. (© 2022. The Author(s).)

Hussein, R. S., et al. (2021). "Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial." International Journal of Fertility & Sterility 15(2): 108-114.
	BACKGROUND: Premature luteinization (PL) is not unusual in in vitro fertilization (IVF) and could not be wholly avoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The study aims to evaluate metformin's efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted in a tertiary university IVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligible women were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500 mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulation triggering, while women in the placebo group received a placebo for the same regimen and duration. The primary outcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondary outcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates. RESULTS: The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulation days, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformin group experienced lower level of serum P (P<0.001) and incidence of PL (10 vs. 23.6%, P=0.001). Moreover, lower progesterone/estradiol (P/E) ratio and progesterone to mature oocyte index (PMOI) (P=0.002 and P=0.002, respectively) were demonstrated in women receiving metformin. Metformin group generated a better rate of goodquality embryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderline significance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04). CONCLUSION: Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL (Registration number: NCT03088631).

Hussein, R. S., et al. (2020). "Fertility Preservation in Women: Indications and Options for Therapy." Mayo Clin. Proc. 95(4): 770-783.
	Fertility preservation (FP) is a vital issue for individuals in either reproductive or prepubescent stage of life when future fertility may be compromised. The objective of any FP intervention is to minimize or eliminate primary disease burden and to ensure maintaining or preserving reproductive health. Fertility potential can be affected by cancer therapy and numerous other factors, including advancing age, metabolic conditions, autoimmune diseases, specific surgical interventions, and sex affirmation procedures. A paradigm shift focusing on quality-of-life issues and long-term survivorship has emerged, especially because of advances in cancer diagnostics and treatment. Several FP techniques have been widely distributed, while others are still in the research stage. In addition, specific procedures and some potentially fertoprotective agents are being developed, aiming to minimize the hazards of gonadal damage caused by cancer therapy and decrease the need for more costly, invasive, and time-consuming FP methods. This review highlights the advances, indications, and options for FP, both experimental and well-established, in females of various age groups. An electronic search in PubMed, Embase, and Google Scholar databases was conducted, including retrospective studies, prospective clinical trials, meta-analyses, original reviews, and online abstracts published up to June 30, 2019. The search terms used included fertility preservation, oncofertility, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. The meeting proceedings of the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology were also hand searched.

Hwang, J. H. and B. Kim (2024). "Comparison of survival outcomes between robotic and laparoscopic radical hysterectomies for early-stage cervical cancer: a systemic review and meta-analysis." Journal of Gynecologic Oncology 35(1): e9.
	Objective: Survival outcomes of robotic radical hysterectomy (RRH) remain controversial. Therefore, we performed a meta-analysis to evaluate survival outcomes between RRH) and laparoscopic radical hysterectomy (LRH) in patients with early-stage cervical cancer. Method(s): Studies comparing between RRH and LRH published up to November 2022 were systemically searched in the PubMed, Cochrane Library, Web of Science, ScienceDirect, and Google Scholar databases. Manual searches of related articles and relevant bibliographies of the published studies were also performed. Two researchers independently extracted data. Studies with information on recurrence and death after minimally invasive radical hysterectomy were also included. The extracted data were analyzed using the Stata MP software package version 17.0. Result(s): Twenty eligible clinical trials were included in the meta-analysis. When all studies were pooled, the odds ratios of RRH for recurrence and death were 1.19 (95% confidence interval [CI]=0.91-1.55; p=0.613; I2=0.0%) and 0.96 (95% CI=0.65-1.42; p=0.558; I2=0.0%), respectively. In a subgroup analysis, the quality of study methodology, study size, country where the study was conducted, and publication year were not associated with survival outcomes between RRH and LRH. Conclusion(s): This meta-analysis demonstrates that the survival outcomes are comparable between RRH and LRH.Copyright © 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Hwang, J. H. and B. W. Kim (2022). "The incidence of postoperative symptomatic lymphocele after pelvic lymphadenectomy between abdominal and laparoscopic approach: a systemic review and meta-analysis." Surgical Endoscopy 36(10): 7114-7125.
	Objective: To evaluate the risks of symptomatic lymphocele after pelvic lymphadenectomy between the laparoscopic and abdominal approach in uterine cervical and endometrial cancer. Method(s): We searched Ovid Medline, Ovid EMBASE, and the Cochrane library through April 2020. We selected the comparative studies contained information on symptomatic lymphoceles in postoperative complications. All articles searched were independently reviewed and selected by two researchers. A meta-analysis was performed using the Stata MP version 16.0 software package. Result(s): A total of 33 eligible clinical trials were ultimately enrolled in this meta-analysis. When all studies were pooled, the odds ratios (OR) of the laparoscopic approach for the risk of symptomatic lymphoceles compared to the abdominal approach was 0.58 [95% confidence interval (CI): 0.42-0.81, p = 0.022, I-squared = 0.0%]. The risk of postoperative symptomatic lymphoceles in the laparoscopic group tended to decrease over time in the cumulative meta-analysis. In the subgroup analysis, there was no evidence for an association between cancer type, quality of the study methodology, hysterectomy type, and postoperative symptomatic lymphoceles. However, in a recently published article, being overweight (body mass index >= 25) and studies conducted in oriental area were associated with a lower incidence of postoperative symptomatic lymphoceles. Conclusion(s): Laparoscopic lymphadenectomy was associated with a significantly lower risk of postoperative symptomatic lymphoceles than abdominal lymphadenectomy (PROSPERO registration number: CRD 42,020,187,165).Copyright © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Hwang Jong, H. and W. Kim Bo (2021). "Comparison of Survival Outcomes after Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Patients with Cervical Cancer." Journal of Minimally Invasive Gynecology 28(5): 971.
	Objective: A meta-analysis was performed to compare survival outcomes including disease-free survival (DFS) between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in patients with cervical cancer.; Data Sources: We searched PubMed, EMBASE, Google scholar, and the Cochrane library for studies published between December 2004 and May 2020. Manual searches of related articles and relevant bibliographies of published studies were also performed.; Methods of Study Selection: Two researchers independently extracted the data. Studies with survival outcome information were included.; Tabulation, Integration, and Results: A total of 36 eligible clinical trials were included in this meta-analysis. When all studies were pooled, the hazard ratio (HR) of LRH for the risk of DFS and overall survival (OS) compared with ARH was 1.24 (95% confidence interval [CI], 1.09-1.41; p = .001; I 2 = 37.5%) and 1.27 (95% CI, 1.04-1.56; p = .020; I 2 = 45.5%), respectively. In a subgroup analysis, significant harmful effects of DFS in patients with LRH increased in studies using the HR presented by the article (HR, 1.41; 95% CI, 1.21-1.64; p <.001), matched retrospective design (HR, 1.49; 95% CI, 1.19-1.88; p = .001), large-scale studies (HR, 1.34; 95% CI, 1.16-1.55; p <.001), and studies published after the Laparoscopic Approach to Cervical Cancer trial (HR, 1.46; 95% CI, 1.25-1.71; p <.001). However, LRH did not affect DFS (HR, 1.04; 95% CI, 0.59-1.81; p = .898) or OS (HR, 0.57; 95% CI, 0.31-1.05; p = .073) of patients with cervical cancer with cervical masses <2 cm.; Conclusion: This meta-analysis demonstrated that LRH was associated with higher recurrence rates than ARH. However, LRH showed similar recurrence and OS among patients with cervical masses <2 cm (Centre for Reviews and Dissemination 42020191713). (Copyright © 2020. Published by Elsevier Inc.)

Hwang Jong, H. and W. Kim Bo (2023). "The incidence of perioperative lymphatic complications after radical hysterectomy and pelvic lymphadenectomy between robotic and laparoscopic approach : a systemic review and meta-analysis." International journal of surgery (London, England) 109(8): 2478-2485.
	Background: Although many studies have reported perioperative complications after radical hysterectomy and pelvic lymph node dissection using robotic and laparoscopic approaches, the risk of perioperative lymphatic complications has not been well identified. The aim of this meta-analysis is to compare the risks of perioperative lymphatic complications after robotic radical hysterectomy and lymph node dissection (RRHND) with laparoscopic radical hysterectomy and lymph node dissection (LRHND) for early uterine cervical cancer.; Materials and Methods: The authors searched the PubMed, Cochrane Library, Web of Science, ScienceDirect, and Google Scholar databases for studies published up to July 2022 comparing perioperative lymphatic complications after RRHND and LRHND while treating early uterine cervical cancer. Related articles and bibliographies of relevant studies were also checked. Two reviewers independently performed the data extraction.; Results: A total of 19 eligible clinical trials (15 retrospective studies and 4 prospective studies) comprising 3079 patients were included in this analysis. Only 107 patients (3.48%) had perioperative lymphatic complications, of which the most common was lymphedema ( n =57, 1.85%), followed by symptomatic lymphocele ( n =30, 0.97%), and lymphorrhea ( n =15, 0.49%). When all studies were pooled, the odds ratio for the risk of any lymphatic complication after RRHND compared with LRHND was 1.27 (95% CI: 0.86-1.89; P =0.230). In the subgroup analysis, study quality, country of research, and publication year were not associated with perioperative lymphatic complications.; Conclusions: A meta-analysis of the available current literature suggests that RRHND is not superior to LRHND in terms of perioperative lymphatic complications. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hwang, J. Y., et al. (2019). "Health Promoting Effects of Red Ginseng Intake: A Systematic Review (P23-008-19)." Current developments in nutrition 3(Suppl 1).
	OBJECTIVES: Although red ginseng is one of the bestselling herbal medicines, little studies have evaluated and summarized the effects of red ginseng intake on human health using a systematic review. METHODS: We systematically searched for epidemiological studies from 1997 to 2018 regarding red ginseng intake and health in the PubMed, DBPIA, and EMBASE databases. A total of 41 related studies were qualitatively reviewed under the four functionalities of red ginseng: immunity enhancement, prevention of metabolic syndrome and diabetes, blood circulation and prevention of hypertension, and menopausal symptom relief. RESULTS: We identified thirteen studies for immunity enhancement, ten prevention of metabolic syndrome and diabetes (reduced postprandial blood glucose levels), nine for blood circulation and prevention of hypertension, and five for menopausal symptom relief. Functional effects of red ginseng may be related to antioxidant effects via fermentation, although some studies have reported inconsistent effects such as insulin sensitivity. CONCLUSIONS: Red ginseng may have potential health promoting effects based on this systematic review. Further meta-analysis study is needed to identify and evaluate whether these potential effects of red ginseng exist. FUNDING SOURCES: This study was supported by the Korea Ginseng Corp.

Hye, r., et al. (2021). "Systematic Review of Art Therapy for Infertile Patients."
	
Hynes Jenna, S. and J. Forman Eric (2023). "Transfer of the fittest: using preimplantation genetic testing for aneuploidy to select embryo(s) most likely to lead to live birth." F&S science 4(2S): 2-6.
	Preimplantation genetic testing for aneuploidy (PGT-A) was developed to identify euploid embryos from a cohort of embryos with unknown ploidy produced during an in vitro fertilization (IVF) cycle. In recent years, the ability of PGT-A to improve IVF outcomes has come into question. The goal of this review was to summarize the major randomized controlled trials (RCTs) and nonselection studies evaluating the benefit of PGT-A to improve the live birth rates (LBRs). We argue that the LBR per transfer is more relevant to the individual patient than the cumulative LBR as a means to minimize the burden of IVF by reducing futile transfers, pregnancy losses, and ongoing aneuploidy. The early RCTs demonstrate improved implantation rates and LBRs with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by the small sample size and a bias toward good-prognosis patients. Further studies using next-generation sequencing found more variable results but did confirm an improvement in the LBRs per transfer in an older population with a higher baseline risk of aneuploidy. The largest RCT to date showed similar cumulative LBRs in the PGT-A and control groups after biopsy and sequential transfer of up to 3 blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Nonselection studies evaluating pregnancy outcomes after transfer of euploid vs. aneuploid embryos demonstrate near-perfect negative predictive value for an aneuploid result to predict live birth. Putative mosaic embryos had similar LBRs compared with euploid embryos. The available RCTs and nonselection studies support the practice of using PGT-A to identify euploid embryos for transfer, especially in an older population, while simultaneously selecting against aneuploid embryos, without negative impact on the total reproductive potential of the cycle. (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Hyun, J. Y., et al. (2024). "Herbal therapeutics for female infertility: A systematic review and meta-analysis." Journal of Ethnopharmacology 319: 117258.
	Ethnopharmacological relevance: Infertility is a global public health issue related to gynecological diseases and psychological disorders such as stress, depression, and fatigue. Prescriptions of various herbs in traditional East Asian medicine (TEAM) have recently gained attention among patients as a complementary alternative therapy for female infertility. However, studies on systemic analysis of the use of herbal medicines according to TEAM patterns or the therapeutic effects of herbal medicines on female infertility are limited. Aim of the study: We aimed to systematically investigate the single herb and TEAM patterns that are commonly used for treating female infertility using network analysis. Additionally, we performed a meta-analysis to assess the effect of herbal medicine on the pregnancy rate in women with infertility. Material(s) and Method(s): PubMed, EMBASE, Korean Studies Information Service System, Science ON, Research Information Sharing Service, and Oriental Medicine Advanced Searching Integrated System were searched for randomized controlled trials (RCTs) reporting the pregnancy rate of herbal medicine for infertility until July 2021. Following identifying the top three herbs used in treating female infertility, a network analysis was performed to reveal the TEAM pattern relationships between each herb. A meta-analysis was performed to evaluate the therapeutic effect of herbal medicine on pregnancy rate. Moreover, the methodological quality of RCTs was analyzed using Consolidated Standards of Reporting Trials (CONSORT) extension guidelines and the Risk of bias (RoB) tool. Result(s): Eighteen RCTs with 2,662 participants were included. Cuscuta chinensis Lam. (Tusizi) is the most commonly used herb for treating female infertility, followed by Angelica gigas Nakai (Danggui) and Cyperus rotundus L. (Xiangfuzi). These herbs were mainly used to treat patients with kidney deficiency or kidney deficiency combined with blood stasis or Phlegm-dampness on the TEAM pattern. The meta-analysis revealed that the effect of herbal medicine led to a significant increase in pregnancy rates compared to the placebo treatment. Adverse events in the included studies were generally mild and infrequent. The methodological quality of RCTs using CONSORT extension was poor, while the RoB of the included RCTs was generally low. Conclusion(s): The findings of this review suggest that herbal medicine will be beneficial for treating female infertility by improving pregnancy rates. However, more carefully designed studies on herbal medicines are encouraged to improve the quality of herbal medicine research in the future.Copyright © 2023 Elsevier B.V.

Iacovelli, V., et al. (2020). "The role of glycosaminoglycans in the management of chronic pelvic pain: a systematic review." Minerva urologica e nefrologica = The Italian journal of urology and nephrology 72(3): 321-331.
	Introduction: Glycosaminoglycans (GAGs) are involved in the pathogenesis of several urologic chronic diseases. Thus, GAGs replenishment therapy is widely reported as a therapeutic tool for chronic pelvic pain (CPP) conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) and prostate pain syndrome/chronic prostatitis. In this article we reviewed the current status of evidence on the clinic applications of glycosaminoglycans (GAGs) in the CPP.; Evidence Acquisition: A literature search from inception was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement to identify clinical trials, randomized controlled trials, meta-analyses, and guidelines.; Evidence Synthesis: A total of 29 papers were identified regarding the use of GAGs in CPP.; Conclusions: GAGs replenishment therapy results are encouraging in chronic forms of pelvic pain even though well-powered randomized clinical trials are needed to better comprehend the exact role of this treatment.

Ianieri Manuel, M., et al. (2021). "Indocyanine green in the surgical management of endometriosis: A systematic review." Acta Obstetricia et Gynecologica Scandinavica 100(2): 189-199.
	Introduction: Endometriosis is a very common disease that affects up to 10% of the female population. The use of indocyanine green (ICG) dye has been proposed to allow the proper localization of endometriotic lesions during surgery. Our purpose is to offer an overview of near-infrared (NIR)-ICG in the surgical treatment of superficial peritoneal endometriosis and deep infiltrating endometriosis.; Material and Methods: Electronic databases were searched, including MEDLINE, Embase, Web of Science, Scopus, ClinicalTrial.gov, OVID and Cochrane Library. The studies were identified with the use of a mesh combination of the following keywords: "indocyanine green", "endometriosis", "deep endometriosis", "robotic surgery", "laparoscopy", "ureter", "rectosigmoid" from 2000 to May 2020. All articles describing the use of ICG applied to endometriosis surgery were considered for review. Only original papers that reported specific experience data on the topic were included. Moreover, video-articles were included in the analysis. Quality and risk of bias were evaluated by two authors, respectively.; Results: Fifty-three studies were reviewed and reviews or comment articles not reporting original data and original articles lacking specific data on the application of ICG in patients affected by endometriosis were excluded. The quality of the 17 studies included was assessed. Eight studies suggested the usefulness of NIR-ICG as a tool in the detection of endometriosis during surgery, and one randomized controlled trial and one prospective study did not confirm the advantage of its use. Eight studies found that NIR-ICG was useful for the evaluation of vascularization in intestinal anastomoses and ureterolysis after surgery for deep infiltrating endometriosis.; Conclusions: NIR-ICG appears useful in the evaluation of vascularization in intestinal anastomoses after segmental resection, confirming its role even after ureterolysis for parametrial deep infiltrating endometriosis. However, its usefulness as a tool in the detection of endometriosis during surgery is inconsistent. (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Ianieri Manuel, M., et al. (2023). "Are ureterolysis for deep endometriosis really all the same? An anatomical classification proposal for ureterolysis: A single-center experience." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 162(3): 1010-1019.
	Objective: Ureteral endometriosis has an incidence of 0.1% to 1%. The type of surgery required is either conservative (ureterolysis) or radical treatment, depending on the degree of ureter infiltration. The incidence of intraoperative and postoperative complications is heterogeneous. Thus, the aim of the current study was to propose a classification of ureterolysis based on the anatomical structure of the ureter and differing complication rates with procedures.; Methods: A total of 139 ureterolysis procedures were included in the study. Patients were divided into three groups according to the depth of ureterolysis required. Differences were recorded across the three types of ureterolysis in terms of intraoperative and postoperative complications.; Results: The incidence of ureteral fistula was reported in 0.7% of cases, with postoperative ureteral stenosis in 2% of type 2 ureterolysis. In the case of type 3 ureterolysis, after conservative procedures, 52.9% of patients required an ureteroneocystostomy to solve the ureteral stenosis.; Conclusion: The risk of ureteral injury and ureteroneocystostomy after conservative procedures appears to be associated with type 3 ureterolysis, probably due to excessive devascularization, secondary to the incision of adventitia. Obviously, these data should be confirmed through a prospective study of a larger number, but our proposed classification can provide the basis for making data from future studies more comparable. (© 2023 International Federation of Gynecology and Obstetrics.)

Ibanez, L., et al. (2023). "Raised Thyroid Stimulating Hormone In Girls With Polycystic Ovary SyndromeEffects Of Randomized Interventions." Journal of the Endocrine Society 7(Supplement 1): A864-A865.
	Introduction: Polycystic ovary syndrome (PCOS) in women associates with raised levels of circulating thyroid stimulating hormone (TSH) and with high rates of gestational complications. A low range of preconception TSH is followed by low rates of gestational complications. It is unknown whether TSH levels are elevated in adolescents with PCOS and, if so, whether traditional or exploratory treatments can lower them into safe preconception range. We investigated TSH in non-obese adolescents with PCOS, including the effects of randomized interventions. Method(s): Morning TSH was a safety marker in randomized pilot studies comparing the effects of an oral contraceptive (OC) versus those of a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET, aiming at a reduction of ectopic fat without necessarily lowering body weight) in non-obese adolescents with PCOS. A posthoc analysis compared: TSH levels in PCOS (N= 62) vs controls; TSH changes on treatment (1 year); TSH levels post treatment (1 year). Result(s): Mean TSH levels were higher in PCOS patients than in control girls (P<0.01). On-treatment TSH levels diverged (P<0.001), remaining elevated on OC, and descending swiftly on SPIOMET, well into safe preconception range. Post-treatment TSH levels were stable in both subgroups. On-treatment changes of circulating TSH associated to those of liver fat (R= 0.307, P= 0.017). Conclusion(s): The endocrine signature of early PCOS is herewith extended to include modestly raised levels of circulating TSH; the normalizing effects of SPIOMET intervention in non-obese adolescents with PCOS are herewith extended to include on- and posttreatment TSH.

Ibrahim, K., et al. (2023). "Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials." BMJ Open 13(10): e069616.
	Objectives: We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3).; Design: Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.; Data Sources: PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.; Eligibility Criteria: Phase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded.; Data Extraction and Synthesis: Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.; Results: 12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported.; Conclusions: The efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied.; Prospero Registration Number: CRD42022307418.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Idahl, A., et al. (2023). "HOPPSA update: changes in the study protocol of Hysterectomy and OPPortunistic SAlpingectomy, a registry-based randomized controlled trial." Trials 24(1): 222.
	Background: The HOPPSA trial is a multi-center national registry-based randomized controlled trial to test the safety and effectiveness of performing opportunistic salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer (EOC). The study protocol was first published in January 2019 and is available at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3083-8 . Here, we report amendments made to the study protocol since commencement of the trial.; Changes in Methods and Analysis: The primary outcomes analyses have been changed. (1) Complications will be analyzed using binomial generalized estimating equation (GEE) with log link function, while the unadjusted analyses according to Miettinen and Nurminen will be performed as a sensitivity analysis. (2) Absolute change in Menopause Rating Scale (MRS) will primarily be analyzed using a mixed effects model, adjusted for baseline MRS and center as a random effect. (3) Time to EOC will be analyzed using the mixed effects Cox regression model with center as random effect, while the unadjusted log-rank test will be performed as a sensitivity analysis. The primary outcome Complications will be based solely on the specific assessment in the GynOp quality registry. The Clavien-Dindo classification will be evaluated as a secondary outcome. Furthermore, MRS is also measured three years postoperatively to better pinpoint the onset of menopausal symptoms.; Discussion: The changes to the protocol mainly concern the analyses of data. No changes to recruitment, randomization, intervention, or follow-up of primary outcomes have been made. An interim analysis during 2021 concluded that the study should continue until the target sample size is reached.; Trial Registration: ClinicalTrials.gov, NCT03045965 . Registered 8 February 2017. (© 2023. The Author(s).)

Idaikkadar, P., et al. (2022). "Non-Surgical Management of Malignant Bowel Obstruction in Advanced Ovarian Cancer patients: A Systematic Review and Meta-Analysis." The American journal of hospice & palliative care 39(7): 838-846.
	Background: Malignant bowel obstruction is a common cause of morbidity and mortality in patients with advanced ovarian cancer. Many patients aren't suitable for, or decline, surgical decompression. The outcomes for this frail group of patients are not well characterized.; Aim: To evaluate survival outcomes of ovarian cancer patients who undergo non-surgical management of malignant bowel obstruction.; Design: Systematic review and meta-analysis.; Data Sources: Online literature search of Pubmed, Embase and Medline libraries up until December 2020. Searching abstracts of scientific meetings, reference lists of included studies and contacting experts in the field.; Selection Criteria: Studies that investigated non-surgical management of confirmed bowel obstruction in advanced ovarian cancer patients were included. All levels of evidence including RCTs, cohort studies and case-series if they included greater than 5 patients.; Data Collection and Analysis: The studies were independently chosen by two reviewers who extracted and analyzed the data separately through OpenMeta Analyst software. Study quality was assessed using the JADAD score and the Newcastle Ottawa Score.; Results: 24 studies met the eligibility criteria for the systematic review and 9 for the meta-analysis. Median survival of patients managed non-surgically for bowel obstruction was 44 days (95% CI 38-49 days, I 2 = 0%, P = 0.128).; Conclusion: The quality of studies was relatively low, however the evidence shows that non-surgical management of bowel obstruction results in a short life expectancy but with controlled symptoms. Where quality of life is the main concern, this may be a feasible and effective strategy.

Iezzoni, L. I. (2022). "Cancer detection, diagnosis, and treatment for adults with disabilities." The Lancet Oncology 23(4): e164-e173.
	About 15% of the global population-more than 1 billion people-have a disability. People with early-onset disability are now living into middle and older ages and are therefore at risk for adult cancer. Overall, disabled people are more disadvantaged in social determinants of health and are more likely to have risk factors associated with cancer than people without disabilities. People with disabilities often experience disparities in breast and cervical cancer screening compared with people who do not have disabilities, and patterns in colorectal cancer screening disparities are inconsistent. The minimal evidence that exists relating to the timeliness of cancer diagnosis, treatment, and outcomes for people with disabilities suggests differential treatment and higher cancer-related mortality than for people without disabilities. Worldwide, disabled people face barriers to obtaining cancer care, including inaccessible medical diagnostic equipment, ineffective communication accommodations, and potentially biased attitudes among clinicians. Ensuring equitable cancer care for people with disabilities will therefore require eliminating not only physical but also attitude-based barriers to their care.Copyright © 2022 Elsevier Ltd

Ijaz, I., et al. (2023). "Evaluation of the efficacy of systemic therapy for advanced uterine leiomyosarcoma: A systematic review, meta-analysis, and meta-regression analysis." Cancer Medicine 12(13): 13894-13911.
	Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta-analysis and meta-regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta-analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta-regression analysis was performed to estimate the association between the study-specific hazard ratios and specific demographic variables. A meta-analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First-line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44-0.52) and second-line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39-0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67-0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63-0.75) showed the greatest benefits when used as first-line and second-line chemotherapies, respectively. Subgroup meta-analysis results revealed that dual-regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III-IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease. (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Ikeda, M. and A. Mori (2021). "Vaginal palpation versus transabdominal ultrasound in the comprehension of pelvic floor muscle contraction after vaginal delivery: a randomised controlled trial." BMC Women's Health 21(1): 53.
	BACKGROUND: Pelvic floor muscles support the pelvic organs and control voiding. The first choice in the repair of pelvic floor function that is damaged during pregnancy and delivery is pelvic floor muscle training, which involves repeated muscle relaxation and contraction. However, as muscle contractions cannot be visualised, it is difficult to assess whether patients understand how to contract them. Therefore, we assessed patients' comprehension of pelvic floor muscle contraction by comparing two teaching methods, vaginal palpation and transabdominal ultrasound, following vaginal delivery. We hypothesised that vaginal palpation is better than transabdominal ultrasound in this regard. METHODS: This randomised controlled trial conducted in facilities in Tokyo, Japan between July 2018 and January 2019 included women aged ≥ 20 years at 4-6 weeks after vaginal delivery. The randomisation involved website-based centralised allocation. The primary outcome was a change in bladder base displacement during pelvic floor muscle contraction before and after training, which was measured using transabdominal ultrasound. Participants performed three contractions for 3 s, and the mean value was used for statistical analysis. The secondary outcome was a change in understanding the contraction before and after training, which was measured using a five-point Likert scale questionnaire. Outcomes were analysed using Welch's t-test. RESULTS: Sixty-five participants were randomly allocated to the vaginal palpation group (n = 32) and transabdominal ultrasound group (n = 33). Baseline characteristics were similar between the groups. Changes in bladder base displacement were not significantly different between the groups (p = 0.181). Within-group analyses showed that bladder base displacement was large in both groups after the respective intervention. There were no significant differences in any of the outcomes between the two groups before and after the intervention. CONCLUSIONS: Vaginal palpation and transabdominal ultrasound might be useful for comprehending pelvic floor muscle contraction after vaginal delivery. TRIAL REGISTRATION: UMIN 000032304. Registered 18 April 2018, https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000036820 .

Ilaria, C., et al. (2023). "The Great Debate: surgical outcomes myomectomy of laparoscopic versus laparotomic approach - A Meta-Analysis."
	
Ilich Jasminka, Z., et al. (2022). "Cardiometabolic Indices after Weight Loss with Calcium or Dairy Foods: Secondary Analyses from a Randomized Trial with Overweight/Obese Postmenopausal Women." Nutrients 14(5).
	The role of dairy foods and calcium/vitamin D supplements in cardiometabolic diseases is unknown. The objective of this secondary analysis is to investigate cardiometabolic risk factors changes after a 6-month weight-loss intervention in overweight/obese postmenopausal women divided in three groups: Ca+vitamin D supplements (S); low-fat dairy foods (D; 4−5 servings/day); or control/placebo pills (C), as complements to hypocaloric diets. The original study focused on bone/body composition. This analysis included blood pressure (BP), and serum triglycerides, lipids (including apoproteins Apo1 and ApoB), adipokines, and C-reactive protein in n = 97 participants who finished with complete data points. Systolic BP decreased 5.1%, 4.8%, and 1.8% in S, D, and C groups, respectively (p < 0.05 for S and D vs. baseline and vs. C at 6 months). Reduction in triglycerides and ratio of total cholesterol (TC)/high-density lipoproteins cholesterol (HDL-C) was the highest in S, while the reduction in TC and LDL-C was the highest in D group (all p < 0.05). Leptin and ApoB significantly decreased and adiponectin and ApoA1 increased in all groups. In conclusion, although the C group’s participants experienced an improvement in some of the cardiometabolic indices with weight loss, those in the S and D groups showed significantly better results in most of the outcomes, indicating the beneficial effects of low-fat dairy foods and/or Ca+vitamin D intake as complements to a hypocaloric diet.

Ilmiah Widia, S., et al. (2023). "Non-pharmacological that most effective to reduce of primary dysmenorrhea intensity in women childbearing age: a literature review." Journal of public health in Africa 14(12): 2349.
	One of the most common female reproductive health problems is primary dysmenorrhea. Data on the incidence of primary dysmenorrhea complained about 50-90% of women in the world. Primary dysmenorrhea data in the US is 30-70%, in Sweden is 30%, in Mexico is 64%, in Italy is 68%, in Jordan is 55.8%, in Turkey is 84.9%, and in Malaysia is 74.5%, in Indonesia is 60-70 and 15% of its, it interferes with daily activities including work. The cause of this is hypercontractility of the myometrium due to excessive secretion of prostaglandins. This study aims to explore the most effective non-pharmacological therapies in reducing the level of primary dysmenorrhea pain in women of childbearing age. The design of this study is a literature review with the PRISMA method. Database Google, Google Scholar, Research gate, Cochran Data Base, Embase, NCBI, Sciendirect, SAGE, Elsevier, Sinta. The population of this study was all full-text international journals indexed by Scopus and national journals indexed by Sinta 1-6 published in 2011-2021 including RCT amount of 114 articles. A sample of 23 articles meets the inclusion criteria and used thematic data analysis. The results of non-pharmacological therapy that effectively overcome primary dysmenorrhea pain, namely the first group with (P=0.000). The conclusions showed that Murrotal Qur'an, yoga, acupressure, counter pressure massage, effleurage massage, consume green coconut water and avocado juice combination with massage were proven to be equally effective in overcoming complaints of primary dysmenorrhea pain quickly without being accompanied by side effects. (Copyright © 2023, the Author(s).)

Ilyin, A. B., et al. (2021). "Comparison of two levonorgestrel-releasing intrauterine systems for the treatment of heavy menstrual bleeding: a randomised, controlled, phase 3 trial." European journal of contraception & reproductive health care 26(6): 491‐498.
	Purpose: To evaluate the levonorgestrel‐releasing intrauterine system Donasert® (also known as Levosert®) compared with the reference product Mirena® for the alleviation of heavy menstrual bleeding (HMB). Materials and methods: A phase 3 multicentre, non‐inferiority, active‐controlled study in non‐menopausal women with HMB (menstrual blood loss [MBL] ≥ 80 mL) as the primary symptom randomised to either Donasert® or Mirena® and followed for 6 months. MBL was evaluated using a validated, modified version of the Wyatt pictogram. Results: Overall, 312 were randomised (158 to Donasert® and 154 to Mirena®). The mean (standard deviation) absolute change in MBL from baseline to 6 months in the per‐protocol population (N = 300) was −130 (71.8) mL and −127 (67.3) mL in the Donasert® and Mirena® groups, respectively; non‐inferiority of Donasert® was confirmed (p‐value <0.0001). Successful treatment of HMB (MBL <80 mL) and a decrease to ≤50% of baseline MBL was achieved in 139/154 (90.3%) and 126/146 (86.3%) participants in the Donasert® and Mirena® groups, respectively and the between‐treatment difference was non‐significant. Most adverse events were mild in severity. Only two device expulsions occurred in the study and there were no uterine perforations. Conclusions: Donasert® has equivalent efficacy and safety during the first 6 months foralleviation of HMB compared to the reference device, Mirena®. Trial registration number: 348 (Clinical Trials Registry of the Ministry of Health of the Russian Federation, http://grls.rosminzdrav.ru/default.aspx).

Im, S. A., et al. (2022). "PETRA: First in class, first in human trial of the next generation PARP1-selective inhibitor AZD5305 in patients (pts) with BRCA1/2, PALB2 or RAD51C/D mutationsTimothy A. Yap." Cancer Research 82(12 Supplement).
	Background: AZD5305 is a potent, highly selective PARP1 inhibitor and trapper with superior preclinical tolerability, target engagement and efficacy vs 1st generation dual PARP1/2 inhibitors (PARPi). This is the first report of the ongoing Phase 1/2a PETRA (NCT04644068) trial. Method(s): Pts with advanced breast, ovarian, prostate or pancreatic cancer bearing germline or somatic BRCA1/2, PALB2 or RAD51C/D mutations received AZD5305 QD PO until disease progression. ECOG PS 0-2 and Hb >=9.0 g/dL were required. Prior PARPi and platinum therapy were permitted. The primary objective was safety; secondary objectives included pharmacokinetics (PK) and pharmacodynamics in tumor and/or blood samples and response by RECIST v1.1, CA125 or PSA. Exploratory genomic analyses included zygosity evaluation and ctDNA response monitoring. Result(s): At data cutoff (Nov 17, 2021), 46 pts received AZD5305 10-90 mg QD (43.5% had prior PARPi; median 3.5 prior lines of therapy). AZD5305 was well tolerated across all doses without DLTs (Table). PK exposures were dose-proportional. Steady-state Ctrough was higher than 1st generation PARPi: specifically 6.3 and 31.9 fold above target effective concentration at 10 and 90 mg, respectively. PARylation inhibition was >=90% at 10-40 mg QD (PBMCs) confirming target engagement. 7/25 (28%) pts had objective responses: 5 RECIST PRs (3 confirmed) and 2 additional pts with PSA50 responses (1 confirmed), including platinum- and PARPi-resistant pts. 13/22 (59%) RECIST-measurable pts had SD or PR up to 51+ weeks. ctDNA declined on treatment in 7/13 (54%) evaluable pts (3 complete, 4 >50% reductions) across doses. Conclusion(s): AZD5305 is a highly selective PARP1 inhibitor and trapper with excellent physiochemical properties and a wide therapeutic index. It led to maximal target engagement and showed promising clinical activity with favorable tolerability at exposures surpassing those of 1st generation PARPi.

Imai, K., et al. (2021). "Assessing the Effectiveness of a Weight Reduction Program in Hospitalized Obese Patients Undergoing Laparoscopic Surgery." Gynecology and Minimally Invasive Therapy 10(1): 44-46.
	Investigate the efficacy of a hospitalized weight reduction program before laparoscopic surgery among high body mass index (BMI) patients with endometrial cancer. The patients were housed in a shared room, received exercise guidance, and restricted to a total caloric intake of 1200 kcal. A physiotherapist and a dietitian provided pedometer and nutritional guidance, respectively. The primary outcome was weight reduction. Among the 16 patients included, 12 (75%) had Stage I endometrial cancer and 10 (62.5%) underwent laparoscopic surgery. Weight and BMI at first consultation were 88.4±10.4 kg and 34.8±3.9 kg/m2, respectively. The rate of weight reduction was 6.5%±2.5%; on average, BMI decreased by 2.1±1.0 kg/m2. The duration from initial consultation to surgery was 39.1±11.4 days. Hospitalization duration until weight reduction was 20.8±8.0 days; there were no surgical complications. Our hospitalized weight reduction program may be effective for obese endometrial cancer patients.

ImmunoGen, I. and G. O. G. Foundation (2022). Mirvetuximab Soravtansine With Bevacizumab Versus Bevacizumab as Maintenance in Platinum-sensitive Ovarian, Fallopian Tube, or Peritoneal Cancer (GLORIOSA).
	No Results Available Drug: Mirvetuximab soravtansine plus Bevacizumab|Drug: Bevacizumab Assess Progression-free survival (PFS)|Assess Overall survival (OS)|Assess Safety and tolerability|Assess second disease progression (PFS2)|Assess Objective Response Rate (ORR)|Assess Duration of response (DOR)|Assess Disease-free survival (DFS)|CA-125 response|Patient-reported outcome health-related quality of life (HRQoL) of disease-related symptoms using the NCCN-FACT Ovarian Symptom Index (NFOSI-18) DRS-P (disease-related symptom subscale - physical). All Phase 3 418 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment IMGN853-0421 April 2029

Imunon and C. Foundation Break Through (2023). Phase II IMNN-001 (Also Known as GEN-1) on SLL With BEV and NACT, Newly Diagnosed Advanced Ovarian, Fallopian Tube or Primary Peritoneal Cancer.
	No Results Available Drug: Paclitaxel|Drug: Carboplatin|Drug: Bevacizumab|Drug: IMNN-001 Minimal Residual Disease|PFS|OS Female Phase 1|Phase 2 50 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 201-21-202 January 30, 2028

Inal, H. A. and Z. O. Inal (2023). "Transobturator tape surgery experience: urodynamic evaluation of 220 patients in a single tertiary center in Turkey." Vojnosanitetski Pregled 80(2): 158-164.
	Background/Aim. Stress urinary incontinence (SUI) is the involuntary leakage of urine after increased in-traabdominal pressure, and it causes a significant public health problem by reducing the quality of life, causing sex-ual dysfunction, and increasing the cost of care due to in-creased morbidity. The aim of the study was to investigate the intra- and postoperative results and complication rates of the transobturator tape (TOT) procedures used for SUI treatments in a tertiary center located in central Turkey. Methods. This prospective study analyzed a total of 220 patients undergoing TOT procedures for SUI. The demo-graphic and clinical characteristics, preoperative and post-operative cystometry values, and operative outcome pa-rameters of the study participants were analyzed. Results. While no significant difference was noted between the preoperative and postoperative periods with respect to re-sidual volume (27.09 +/- 8.51 mL vs. 26.01 +/- 3.51 mL, p = 0.125), there were significant differences in terms of the first urinary urge (142.61 +/- 20.25 mL vs. 145.64 +/- 20.91 mL, p < 0.001), maximum bladder capacity (423.70 +/- 38.43 mL vs. 402.32 +/- 39.46 mL, p < 0.001), the Q-tip an-gle (45.54 +/- 5.330 vs. 43.81 +/- 6.150, p = 0.001), the maxi-mum flow rate (37.65 +/- 11.54 mL/s vs. 24.38 +/- 9.26 mL/s, p < 0.001), average flow rate (19.92 +/- 9.64 mL/s vs. 14.77 +/- 8.71 mL/s, p < 0.001), the number of urinations in the daytime (7.29 +/- 1.35 vs. 6.58 +/- 1.29, p < 0.001), and the number of urinations at nighttime (1.48 +/- 1.01 vs. 0.92 +/- 0.83, p < 0.001). Conclusion. The TOT procedure im-proves the quality of life of SUI patients and can reduce morbidity. Nevertheless, additional studies are needed to corroborate our findings and determine the long-term ef-fects.Copyright © 2023 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Inc and T. Acer (2022). Dose-ranging, PK, Safety, Efficacy Study of Osanetant in Patients With Moderate/Severe VMS Associated With Menopause.
	No Results Available Drug: ACER-801 50 mg BID|Drug: ACER-801 100 mg BID|Drug: ACER-801 200 mg BID|Drug: Placebo Peak Plasma Concentration (Cmax) of ACER-801|Time to reach maximum concentration (tmax) of ACER-801|Area under the concentration curve from dosing to the time of the last measured concentration (AUClast) of ACER-801|Area under the concentration curve from t0 to infinite time (AUCinf) of ACER-801|Metabolite:parent ratio of Cmax (MRCmax) of ACER-801|Metabolite:parent ratio of AUC (MRauc) of ACER-801|Half-life (t1/2) of ACER-801|Accumulation ratio for Cmax (ARcmax) of ACER-801|Accumulation ratio for AUC (ARcauc) of ACER-801|Peak Plasma Concentration (Cmax) of ACER-801 metabolite|Time to reach maximum concentration (tmax) of ACER-801 metabolite|Area under the concentration curve from dosing to the time of the last measured concentration (AUClast) of ACER-801 metabolite|Area under the concentration curve from t0 to infinite time (AUCinf) of ACER-801 metabolite|Metabolite:parent ratio of Cmax (MRcmax) of ACER-801 metabolite|Accumulation ratio for AUC (MRauc) of ACER-801 metabolite|Half-life (t1/2) of ACER-801 metabolite|Accumulation ratio for Cmax (ARcmax) of ACER-801 metabolite|Accumulation ratio for AUC (ARcauc) of ACER-801 metabolite|Number of patients with a clinically significant change from baseline in abnormalities detected during physical examination|Number and percentage of Adverse Events ≥ 5%|Number and percentage of Serious Adverse Events (SAE)|Number and percentage of subjects who discontinued from the study|Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: HEMATOLOGY|Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: COAGULATION|Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: SERUM CHEMISTRY|Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: HORMONES|Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: BONE DENSITY MARKERS|Number of subjects with a clinically significant change from baseline for clinical laboratory evaluations: URINALYSIS|Change in frequency of vasomotor symptoms (hot flashes) from baseline|Change in severity of vasomotor symptoms (hot flashes) from baseline|Change in severity score vasomotor symptoms (hot flashes) from baseline Female Phase 1|Phase 2 49 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment ACER-801-201 March 4, 2023

Inc and S. Aston (2023). Adjuvant Therapeutic Cancer Vaccine (AST-201, pUMVC3-hIGFBP-2) in Patients With Advanced Ovarian Cancer.
	No Results Available Biological: AST-201|Drug: Paclitaxel|Drug: Carboplatin|Drug: Placebo|Drug: rhuGM-CSF(Granulocyte-Macrophage Colony-Stimulating Factor) Progression-Free Survival (PFS)|2-year PFS rate|Overall Survival (OS)|AST-201 specific immunogenicity by Interferon gamma (IFN-gamma) enzyme-linked immunospot (ELISpot )|Number of participants with Adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0) All Phase 2 98 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment PN-201-22 November 15, 2027

Inc, et al. (2022). Study to Evaluate the Pharmacodynamics and Efficacy of Leuprolide Tablets (Ovarest®) in Women With Endometriosis.
	No Results Available Drug: Leuprolide Oral Tablet - 120 mg - QD- Treatment A|Drug: Leuprolide Oral Tablet - 80 mg - QD - Treatment B|Drug: Leuprolide Oral Tablet - 60 mg - QD - Treatment C|Drug: Leuprolide Oral Tablet - 60 mg - BID - Treatment D|Drug: Leuprolide Oral Tablet - 40 mg - BID - Treatment E Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 20 pg/mL|Suppression of ovulation (as evidenced by progesterone levels <3 ng/mL)|Number of vaginal (menstrual) bleeding days|Composite Pelvic Signs and Symptoms (CPSS) scores|(Pre-dose leuprolide level) Subject incidence of Leuprolide below detectable level|Luteinizing hormone (LH) levels|Follicle Stimulating Hormone (FSH) levels Female Phase 2 16 Industry|Other Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment LOPDT-ENDO-02 May 2022

Inc and P. Fusion (2022). A Study of 225Ac -FPI-1966 in Participants With Advanced Solid Tumours.
	No Results Available Drug: [225Ac]-FPI-1966|Drug: [111In]-FPI-1967|Biological: vofatamab Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.|Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966|Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)|Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.|Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.|Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1|Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images|Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)|Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.|Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody|Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.|Phase 1 and 2: Half-life for radioactivity and targeting antibody.|Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab|Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.|Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.|Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab All Phase 1|Phase 2 6 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment FPI-1966-101 September 8, 2023

Inc, et al. (2023). GEnetic Testing in Elective Single Embryo Transfer (GETSET): A Randomized Clinical Trial.
	No Results Available Other: Preimplantation genetic testing for aneuploidy (PGTA) Ongoing Pregnancy Rate|Miscarriage Rate Female Not Applicable 240 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment GPCL 20232892 November 15, 2025

Inc, A., et al. (2021). A Phase II Study of Balstilimab Independently or in Combination With Zalifrelimab in Advanced Cervical Cancer.
	No Results Available Drug: Balstilimab|Drug: Balstilimab + Zalifrelimab Objective Response Rate (ORR) Of Balstilimab Monotherapy Per Independent Review Committee (IRC) Assessment Based Upon Response Evaluation Criteria In Solid Tumours (RECIST) 1.1|ORR Of Balstilimab Monotherapy Per Investigator Assessment Based Upon RECIST 1.1|Disease Control Rate (DCR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1|Duration of Response (DOR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1|Time to Response (TTR) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1|Progression-free Survival (PFS) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1|Overall Survival (OS) Of Balstilimab Monotherapy Per IRC And Investigator Assessment Based Upon RECIST 1.1|ORR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1|DCR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1|DOR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1|TTR Of Combined Therapy Of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1|PFS Of Combined Therapy Of Balstilimab and Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1|OS Of Combined Therapy of Balstilimab And Zalifrelimab Per IRC And Investigator Assessment Based Upon RECIST 1.1|Peak Plasma Concentration (Cmax) Of Balstilimab And Zalifrelimab|Time To Peak Plasma Concentration (Tmax) Of Balstilimab And Zalifrelimab|Half-life (T1/2) Of Balstilimab And Zalifrelimab|Area Under The Plasma Concentration Versus Time Curve From The Time Of Administration To The Last Measurable Concentration (AUC0-t) Of Balstilimab And Zalifrelimab|Number Of Participants With Anti-drug Antibodies For Balstilimab And Zalifrelimab|Number Of Participants With Treatment-emergent Adverse Events Female Phase 2 177 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment C-750-CN01 December 30, 2024

Inc, A. and T. Groups European Network of Gynaecological Oncological (2021). Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer (BRAVA).
	No Results Available Drug: Balstilimab (BAL)|Drug: Topotecan|Drug: Vinorelbine|Drug: Gemcitabine|Drug: Irinotecan|Drug: Pemetrexed Overall survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy|Overall survival in all patients randomized to BAL vs Investigator's Choice chemotherapy|Progression-free survival in patients with PD-L1 positive tumors randomized to BAL vs Investigator's Choice chemotherapy|Progression-free survival in all patients randomized to BAL vs Investigator's Choice chemotherapy|Objective response rate (ORR) to BAL and to IC chemotherapy in patients with PD-L1 positive tumors|Objective response rate (ORR) to BAL and to IC chemotherapy in all patients' tumors Female Phase 3 0 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment C-700-03 October 22, 2021

Inc Aspen, U. S. A. and G. Incorporated Aspen (2021). A Randomized Controlled Phase 2 Study to Determine Lowest Efficacious Dose of Ovestin in Vulvar and Vaginal Atrophy.
	No Results Available Drug: Estriol|Drug: Placebo Vaginal Maturation Index|Vaginal pH|Most Bothersome Symptom|Incidence of adverse events Female Phase 2 0 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment CLINTECUS-19-OVDFP2 May 15, 2023

Inc Astellas, P. (2021). A Study to Find the Best Dose of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause.
	No Results Available Drug: Fezolinetant|Drug: Placebo Mean change from baseline in the frequency of mild, moderate and severe vasomotor symptom (VMS)|Mean change from baseline in the frequency of mild, moderate and severe VMS|Number of participants with Adverse Events (AEs)|Change from baseline in endometrial thickness|Number of participants with laboratory value abnormalities and/or AEs|Number of participants with vital sign abnormalities and/or AEs|Number of participants with electrocardiogram (ECG) abnormalities and/or AEs|Number of participants with suicidal ideation and/or behavior as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Female Phase 2 147 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment 2693-CL-0206|jRCT2031210334 December 23, 2022

Inc Carisma, T. (2021). CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors.
	No Results Available Biological: CT-0508|Biological: Pembrolizumab Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors.|Assess the feasibility of manufacturing CT-0508 by describing the percentage of products passing release criteria.|Assess the safety and tolerability of CT-0508 in combination with pembrolizumab by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors (CT-0508 and pembrolizumab substudy only)|Estimate the objective response rate (ORR), according to RECIST v1.1, of at least 1 dose of CT-0508 among subjects with HER2 overexpressing solid tumors.|Estimate progression-free survival (PFS). All Phase 1 48 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 101 December 2024

Inc, H., et al. (2024). A Novel Medical System for Quantitative Diagnosis and Personalized Precision Botulinum Neurotoxin Injection in Chronic Pelvic Pain Management.
	The purpose of this study is to evaluate if it is possible to use intravaginal high-density surface electromyography to guide Botulinum neurotoxin (BoNT) injection to treat pelvic floor muscle overactivity that complicates Chronic Pelvic Pain (CPP). Primary Purpose : Treatment Allocation : Randomized Interventional Model : Crossover Assignment Masking : Double (InvestigatorOutcomes Assessor) Outcome: Hypertonic metrics of the pelvic muscles defined by intra-vaginal surface EMG

Inc Karyopharm, T., et al. (2023). Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma.
	No Results Available Drug: Selinexor|Drug: Matching Placebo for selinexor Progression Free Survival (PFS) Assessed by Investigator as per RECIST v1.1|Overall Survival (OS)|Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs|Number of Participants with Clinically Significant Changes in Clinical Laboratory Values, Vital Signs and Physical Examination Reported as an Adverse Event|Number of Participants With Severity of Adverse Event According to Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0|Time to First Subsequent Therapy (TFST)|Time to Second Subsequent Therapy (TSST)|Progression-free Survival After Consecutive Treatment (PFS2)|Progression-free Survival (PFS) Assessed by a Blinded Independent Central Review (BICR), per RECIST v1.1|European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) All Phase 3 220 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment XPORT-EC-042|GOG-3083|ENGOT-EN20 January 31, 2028

Inc, K. G. B. and I. a wholly owned subsidiary of Zentalis Pharmaceuticals (2022). A Study of ZN-c3 and Niraparib in Subjects With Platinum-Resistant Ovarian Cancer.
	No Results Available Drug: ZN-c3|Drug: Niraparib Phase 1: Incidence and severity of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects during Cycle 1|Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Progression Free Survival at 4 months|Phase 2: To investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate|To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Duration of response|To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Clinical Benefit Rate|To further investigate the antitumor activity of ZN-c3 in combination with niraparib - Objective Response Rate|To investigate the OS of subjects receiving ZN-c3 in combination with niraparib|To investigate the safety and tolerability of ZN-c3 in combination with niraparib|To evaluate changes in Patient Reported Outcomes (PROs) and quality of life|To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Maximum Plasma Concentration|To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Area under the plasma concentration-time curve from 0 to 24h|To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Trough concentration|To investigate the plasma PK of ZN-c3 and niraparib when given in combination - Time to maximum plasma concentration Female Phase 1|Phase 2 138 Industry Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ZN-c3-006|GOG-3067|2021-004161-13 November 2023

Inc, K. G. B. and I. a wholly owned subsidiary of Zentalis Pharmaceuticals (2022). A Study of ZN-c3 in Subjects With High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer.
	No Results Available Drug: ZN-c3 Frequency of TEAEs|Severity of TEAEs|Incidence of dose modifications|Overall Response Rate defined by the revised RECIST v1 .1. and assessed by ICR.|Overall Response Rate as defined by the revised RECIST v1 .1. and assessed by ICR and the Investigator.|Duration of Response as defined by the revised RECIST v1 .1. and assessed by ICR and the Investigator.|Progression Free Survival as defined by the revised RECIST v1 .1. and assessed by ICR and the Investigator.|Clinical Benefit Rate as defined by the revised RECIST v1 .1. and assessed by ICR and the Investigator.|Time To Response as defined by the revised RECIST v1 .1. and assessed by ICR and the Investigator. All Phase 2 90 Industry Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ZN-c3-005 October 31, 2025

Inc, S. and Genmab (2021). Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer.
	No Results Available Drug: tisotumab vedotin|Drug: topotecan|Drug: vinorelbine|Drug: gemcitabine|Drug: irinotecan|Drug: pemetrexed Overall survival (OS)|Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator|Confirmed objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator|Time-to-response (TTR) as assessed by the investigator|Duration of response (DOR) as assessed by the investigator|Incidence of adverse events (AEs)|Health-related quality of life as assessed by EQ-5D-5L index|Health-related quality of life as assessed by EQ-5D visual analog scale (VAS)|Health-related quality of life as assessed by EORTC-QLQ-C30|Health-related quality of life as assessed by EORTC-QLQ-CX24 Female Phase 3 556 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment SGNTV-003|ENGOT cx-12|GOG-3057 February 28, 2028

Inci Melisa, G., et al. (2023). "The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(8): 1304-1309.
	Background: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity.; Primary Objective: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery.; Study Hypothesis: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity.; Trial Design: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls.; Inclusion Criteria: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway.; Exclusion Criteria: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis.; Primary Endpoint: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery.; Sample Size: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance).; Estimated Dates for Completing Accrual and Presenting Results: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024.; Trial Registration: NCT05256576.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Inci-Turan, M. G., et al. (2022). "IMPLEMENTATION OF A TRI-MODAL PREHABILITATION INTERVENTION - KOREINNOVATION: THE FIRST PROSPECTIVE CLINICAL TRIAL TO ASSESS A PERIOPERATIVE PATHWAY TO REDUCE POSTOPERATIVE COMPLICATIONS IN OVARIAN CANCER PATIENTS." International Journal of Gynecological Cancer 32(Supplement 2): A297-A298.
	Introduction/Background The effectiveness of prehabilitation in improving physical capacity for patients undergoing surgery has been shown for patients in orthopedic, abdominal, or cardiological surgeries. Ovarian cancer patients have an exceptionally high risk for severe postoperative complications due to the extent of the surgical treatment, often including multivisceral resection. We report our first experiences of implementing a tri-modal prehabilitation intervention as part of the KORE-INNOVATION trial Methodology KORE-INNOVATION is an ongoing clinical trial to implement and assess an innovative perioperative care pathway to reduce complications (primary endpoint) for patients undergoing surgery for ovarian cancer through the implementation of a prehabilitation strategy combined with the 'enhanced recovery after surgery' (ERAS)-pathway. The prehabilitation intervention consists of three modules: a personalized empowerment intervention, a personalized physical exerciseprogram-, and a personalized metabolic screening and nutrition intervention. Before prehabilitation, a complex baseline assessment, consisting of the Fried frailty assessment, metabolic and physical assessments, and detailed patient history, is performed to develop a personalized prehabilitation plan targeting individual deficits (figure 1). Results Prehabilitation ranged from one to three weeks and was overseen by a multi professional and interdisciplinary KORE team of physicians, nurses, physiotherapists, and nutritionists. The majority of patients conducted prehabilitation as outpatients. Weekly phone calls were made to monitor patients' adherence and adjust treatment plans, if necessary. Patients reported feeling more capacitated and resilient after undergoing the prehabilitation program. Conclusion A structured, individualized prehabilitation program delivered through a specialized multi professional team presents an opportunity to prepare patients holistically for the stressful experience of debulking surgery and might contribute to faster postoperative reconditioning. Prehabilitation is an important addition to the ERAS pathway and should be considered a relevant part of perioperative care.

Ines, S., et al. (2021). "Educational programs and sexual counselling for postmenopausal female sexual dysfunction: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Ingham, M., et al. (2023). "Phase II Study of Olaparib and Temozolomide for Advanced Uterine Leiomyosarcoma (NCI Protocol 10250)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(25): 4154-4163.
	Purpose: Uterine leiomyosarcoma (uLMS) is an aggressive subtype of soft-tissue sarcoma with frequent metastatic relapse after curative surgery. Chemotherapy provides limited benefit for advanced disease. Multiomics profiling studies have identified homologous recombination deficiency in uLMS. In preclinical studies where olaparib and temozolomide provided modest activity, the combination was highly effective for inhibiting uLMS tumor growth.; Patients and Methods: NCI Protocol 10250 is a single-arm, open-label, multicenter, phase II study evaluating olaparib and temozolomide in advanced uLMS. Patients with progression on ≥1 prior line received temozolomide 75 mg/m 2 orally once daily with olaparib 200 mg orally twice a day both on days 1-7 in 21-day cycles. The primary end point was the best objective response rate (ORR) within 6 months. A one-stage binomial design was used. If ≥5 of 22 responded, the treatment would be considered promising (93% power; α = .06). All patients underwent paired biopsies that were evaluated with whole-exome sequencing (WES)/RNAseq and a RAD51 foci formation assay.; Results: Twenty-two patients were evaluable. The median age was 55 years, and 59% had received three or more prior lines. Best ORR within 6 months was 23% (5 of 22). The overall ORR was 27% (6 of 22). The median progression-free survival (mPFS) was 6.9 months (95% CI, 5.4 months to not estimable). Hematologic toxicity was common (grade 3/4 neutropenia: 75%; thrombocytopenia: 32%) but manageable with dose modification. Five of 16 (31%) of tumors contained a deleterious homologous recombination gene alteration by WES, and 9 of 18 (50%) were homologous recombination-deficient by the RAD51 assay. In an exploratory analysis, mPFS was prolonged for patients with homologous recombination-deficient versus homologous recombination-proficient tumors (11.2 v 5.4 months, P = .05) by RAD51.; Conclusion: Olaparib and temozolomide met the prespecified primary end point and provided meaningful clinical benefit in patients with advanced, pretreated uLMS.

Innovation, G. I., et al. (2021). GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors.
	No Results Available Drug: GI-101|Drug: Pembrolizumab (KEYTRUDA®)|Drug: Lenvatinib|Radiation: Local Radiotherapy|Drug: GI-101A Incidence and nature of Dose-Limiting Toxicity (DLTs)|Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)|Objective Response Rate (ORR) according to RECIST version 1.1|Peak plasma concentration (Cmax) of GI-101/GI-101A|Half-life of GI-101/GI-101A (T1/2)|Area under the plasma concentration versus time curve (AUC) of GI-101/GI-101A|Disease control rate (DCR) according to RECIST version 1.1|Duration of objective Response (DoR) according to RECIST version 1.1|Time to Tumor Response (TTR) according to RECIST version 1.1|Progression-Free Survival (PFS) according to RECIST version 1.1|ORR per iRECIST guidelines|DCR per iRECIST guidelines All Phase 1|Phase 2 430 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GII-101-P101 (MK-3475-B59)|KEYNOTE-B59 October 2026

Innovations, J. S. P. (2021). The Mollie Study, a Study to Evaluate the Safety and Efficacy of the Mollie Medical Device.
	No Results Available Device: Mollie device Dyspareunia Alleviation Female Not Applicable 111 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment CIP-01 April 30, 2023

Insin, P., et al. (2021). "Prevention of venous thromboembolism in gynecological cancer patients undergoing major abdominopelvic surgery: A systematic review and network meta-analysis." Gynecologic Oncology 161(1): 304-313.
	Objective: Although thromboprophylaxis is recommended to reduce death and disability from venous thromboembolism (VTE), it remains underused due to a perceived risk of bleeding, especially in major abdominopelvic surgical patients.; Methods: We conducted a systematic literature review to identify all eligible randomized controlled trials (RCTs), searching MEDLINE and Scopus databases through November 25, 2020. RCTs published in any language were eligible if they studied in gynecological cancer patients undergoing major abdominopelvic surgery and assessed efficacy of mechanical and pharmacological interventions. Studies with insufficient data for pooling or those comparing different doses/schedules of interventions were excluded. Outcomes of interest were composite VTE (ie, deep vein thrombosis or pulmonary embolism) and major bleeding. Relevant data were extracted for direct and network meta-analyses. Risk ratios (RR) and 95% confidence interval (CI) were estimated and the best intervention probability calculated for each outcome. This study was registered with PROSPERO (CRD42019145508).; Results: We identified 1990 studies; 20 RCTs (4970 patients) were eligible. The overall risk of bias was of some concern. In direct meta-analyses, antithrombins were superior to unfractionated heparin in preventing composite VTE (RR 0.69; 95% CI 0.48-0.99), with no difference detected in the rate of major bleeding for any pairwise comparison. In network meta-analyses, graduated compression stockings plus low-molecular-weight heparin (LMWH) was top-ranked for prevention of composite VTE, whereas sequential compression devices (SCD) ranked second, after no treatment, for major bleeding. In a clustered ranking plot, SCD plus LMWH provided optimal balance between efficacy and safety.; Conclusions: SCD plus LMWH might be safe and effective in VTE prevention following gynecological cancer surgery. However, the patient's bleeding risk should be considered to balance the risk and benefit of treatment.; Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Institute Allegheny Singer, R. and H. University Johns (2024). Home Biofeedback or Pelvic Floor Physical Therapy for Postpartum Urinary Incontinence.
	No Results Available Device: Pericoach® by Analytica|Other: Pelvic Floor Physical Therapy|Other: Questionnaires-No Intervention Determine the impact of both interventions on urinary incontinence-related quality of life using validated questionnaire|Determine overall pelvic floor symptoms measured by validated questionnaire|Determine changes in sexual function following intervention measured by validated questionnaire|Determine the patient impression of symptom improvement using validated questionnaire Female Not Applicable 70 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care POUT/IRB00297309 January 2026

Institute Lawson Health, R. and S. Ontario Academic Medical Organization of (2021). Hypofractionated External-beam RadiOtherapy for Intact Cervical Cancer (HEROICC-Trial): A Feasibility Study.
	No Results Available Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Experimental|Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Standard of Care|Drug: Concurrent Chemotherapy Investigate the feasibility in the Canadian Health Care System|Tumour response based on imaging Female Phase 2 48 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Screening HEROICC|ReDA ID#10482 December 14, 2028

Institute Medstar Health, R. (2023). PRP Injections for Genitourinary Syndrome of Menopause.
	No Results Available Procedure: Injection of platelet-rich plasma|Procedure: Injection of saline Female Sexual Function Index|Patient Global Impression of Improvement (PGI-I)|Visual analog scale for vaginal dryness (VAS)|Urinary Distress Inventory (short form) (UDI-6) Female Not Applicable 30 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Single (Participant)|Primary Purpose: Treatment STUDY00006805 December 2024

Institute Medstar Health, R. and S. Health Patty Brisben Foundation For Women's (2023). Transvaginal Low-level Laser Therapy to Improve Pelvic Pain and Sexual Function in Patients With Endometriosis.
	No Results Available Device: Transvaginal photobiomodulation|Device: Sham therapy Mean change in pelvic pain|Change in Female Sexual Function Index (FSFI) scores|Change in Short Form-McGill Pain Questionnaire (SF-MPQ)|Change in number of Sexually Satisfying Experiences (SSE)|Change in clinic pain scores Female Not Applicable 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment STUDY00005330 May 2024

Institute National, C. (2021). Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer.
	No Results Available Drug: Cisplatin|Drug: Elimusertib|Drug: Gemcitabine Hydrochloride Incidence of adverse events|Recommended phase 2 dose (RP2D) of BAY 1895344|Pharmacokinetic (PK) parameter - maximum concentration (Cmax)|PK parameter - area under the concentration-time curve (AUC)|Deoxyribonucleic acid (DNA) damage repair (DDR) mutations|ATM expression|Response rate|Progression-free survival (PFS) All Phase 1 74 NIH Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2020-05428|PHI-117|10404|UM1CA186717 December 31, 2024

Institute National, C. (2022). Testing the Combination of ZEN003694 and Nivolumab With or Without Ipilimumab in Solid Tumors.
	No Results Available Drug: BET Bromodomain Inhibitor ZEN-3694|Procedure: Biopsy|Procedure: Biospecimen Collection|Procedure: Computed Tomography|Biological: Ipilimumab|Procedure: Magnetic Resonance Imaging|Biological: Nivolumab|Procedure: Positron Emission Tomography|Procedure: X-Ray Imaging Safety and tolerability|Phase 2 recommended dose for the combined regimens|Objective response rate (ORR)|Progression-free survival|Overall survival|Incidence of adverse events|Clinical benefit|Whole exome sequencing|Next generation sequencing ribonucleic acid sequencing|PD-L1 expression in tumor cells and tumor-associated immune cells|Multiplex analysis of tumor infiltrating immune cells|Pharmacokinetic (PK) parameters|Phenotypic characteristics of peripheral blood mononuclear cells over treatment|Circulating tumor deoxyribonucleic acid|Pro-inflammatory and anti-inflammatory cytokines analyses All Phase 1 66 NIH Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2021-02850|HCC#21-211|10433|UM1CA186690 January 1, 2026

Institute National, C. and C. Center National Institutes of Health (2021). A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers.
	No Results Available Drug: Bintrafusp Alfa|Drug: NHS-IL12|Drug: Entinostat Ojective response rate (ORR) of triple combination|Determine RP2D of entinostat|Safety of Triple Combination Therapy|Progression-Free Survival (PFS)|Hospitalization due to AEs attributed to PD|Duration of Response (DoR) All Phase 1|Phase 2 90 NIH Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 210007|21-C-0007 December 13, 2024

Institute National, C. and N. R. G. Oncology (2021). Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents.
	No Results Available Procedure: Biospecimen Collection|Drug: Cediranib Maleate|Procedure: Computed Tomography|Procedure: Computed Tomography with Contrast|Biological: Durvalumab|Procedure: Echocardiography|Procedure: Magnetic Resonance Imaging|Procedure: Multigated Acquisition Scan|Drug: Olaparib|Drug: Paclitaxel|Drug: Pegylated Liposomal Doxorubicin Hydrochloride|Drug: Topotecan Hydrochloride Progression free survival|Objective response rate|Duration of response|Overall survival|Incidence of adverse events Female Phase 2 149 NIH|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2021-00615|NRG-GY023|U10CA180868 January 8, 2025

Institute National, C. and N. R. G. Oncology (2022). Comparing Standard of Care Chemotherapy Treatment to the Combination of Copanlisib and Olaparib for Recurrent Platinum Resistant Ovarian Cancer That Has Progressed Through PARP Inhibitor Therapy.
	No Results Available Procedure: Computed Tomography|Drug: Copanlisib Hydrochloride|Procedure: Magnetic Resonance Imaging|Drug: Olaparib|Drug: Paclitaxel|Drug: Pegylated Liposomal Doxorubicin Hydrochloride|Drug: Topotecan Hydrochloride Progression free survival (PFS)|Objective response rate (ORR)|Overall survival (OS)|Incidence of adverse events Female Phase 2 0 NIH|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2022-02228|NRG-GY029|U10CA180868 March 17, 2023

Institute National, C. and N. R. G. Oncology (2022). Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma.
	No Results Available Drug: Carboplatin|Procedure: Echocardiography|Drug: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab|Procedure: Multigated Acquisition Scan|Drug: Paclitaxel|Other: Quality-of-Life Assessment|Drug: Trastuzumab/Hyaluronidase-oysk Progression free survival (Phase II)|Incidence of dose limiting toxicities (Phase II)|Overall survival (Phase III)|Objective response rate (ORR)|Duration of objective response|Incidence of adverse events (AEs)|HER2 expression|Quality of life Female Phase 2|Phase 3 525 NIH|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2022-01540|NRG-GY026|U10CA180868 October 31, 2027

Institute National, C. and N. R. G. Oncology (2023). Testing the Addition of the AKT Inhibitor, Ipatasertib, to Treatment With the Hormonal Agent Megestrol Acetate for Recurrent or Metastatic Endometrial Cancers.
	No Results Available Procedure: Biospecimen Collection|Procedure: Computed Tomography|Drug: Ipatasertib|Procedure: Magnetic Resonance Imaging|Drug: Megestrol Acetate Incidence of adverse events (AEs) (Phase Ib)|Maximum tolerated dose for phase II (Phase Ib)|Progression free survival (PFS) (Phase II)|Incidence of AEs (Phase II)|Pharmacokinetics of ipatasertib + megestrol acetate (Phase Ib)|Objective response rate (ORR) (Phase II)|Biomarkers (Phase II) Female Phase 1|Phase 2 96 NIH|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2022-07505|NRG-GY028|U10CA180868 January 31, 2027

Institute National, C. and N. R. G. Oncology (2023). Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial.
	No Results Available Procedure: Biopsy|Procedure: Biospecimen Collection|Procedure: Bone Marrow Aspiration and Biopsy|Procedure: Computed Tomography|Procedure: Echocardiography|Procedure: Multigated Acquisition Scan|Drug: Olaparib|Drug: Selumetinib Sulfate Progression-free survival (PFS)|Incidence of adverse events (AE)|Objective response rate (ORR) between two arms|ORR in crossover patients|Duration of response of both arms Female Phase 2 165 NIH|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCI-2022-06841|EAY191-N4|U10CA180868 September 30, 2024

Institute The Netherlands, C. (2023). Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For LAVC.
	No Results Available Drug: Paclitaxel and Carboplatin|Combination Product: Chemoradiation Loco-regional control after 24 months per completed treatment including salvage treatment|Disease-related treatment failure|Disease free survival|Patterns of recurrence of disease|Overall survival|Treatment related death|Prevention of trimodal treatment|Functional organ preservation|Short term and long term complications Female Phase 2 98 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment M22VL2 September 1, 2029

Institutet, K. (2022). A Clinical Trial for Chlorhexidine as Treatment for Vulvovaginal Candidiasis.
	No Results Available Drug: Chlorhexidine Gluconate|Drug: Fluconazole Proportion of women in each group that has cleared the vulvovaginal infection|Prophylactic effect|Adverse events|Symptom score|Examination score|Vaginal lactobacillus content|Infection relapse Female Phase 2 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Chlorhex-KKDS-2021 December 31, 2025

Interdonato, M. L., et al. (2022). "Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery: An Italian initial experience." Frontiers in Medicine 9: 1018232.
	Background: The aim of this study is to evaluate the initial feasibility, safety, and outcomes of hysterectomy performed by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) at three institutions in Italy. Material(s) and Method(s): All women who underwent vNOTES hysterectomy +/- salpingo-oophorectomy for benign indications at three tertiary referral medical centers between July 2019 and April 2021 were included in a retrospective analysis. All vNOTESs were performed with the use of Alexis and Vpath Gel paths (Applied Medical). Perioperative data were extracted from patient records. Patient satisfaction and dyspareunia were prospectively inquired about at 60 days and 6 months. Result(s): Forty-six patients underwent vNOTES in the study period. Indications for surgery included myomas +/- metrorrhagia (52.2%), H-Sil/in situ cervical cancer (10.7%), adenomyosis +/- metrorrhagia (8.7%), BRCA 1-2 mutations (6.5%), endometrial hyperplasia (6.5%), ovarian cyst + history of breast cancer (6.5%), metrorrhagia (6.5%), and hydatidiform mole (2.2%). The mean operation time was 91.1 (+/-32.6) minutes. The mean hemoglobin drop was 1.2 (+/-0.8). The mean visual analog scale at 24 h for post-operative pain was 3.3 (+/-1.8). Secondary to our limited experience with the surgical technique, we favor discharge only from day 1. The mean length of hospital stay was 2 (+/-1.4) days. Two conversions to conventional laparoscopy were reported (4.3%), due to an obliterated pouch of Douglas and a preoperative complication. Two post-operative complications were reported (4.3%). Overall, our data on peri- and post-operative outcomes are similar to those already published for vNOTES. Conclusion(s): Our initial experience suggests that introducing vNOTES as an alternative to conventional surgery is feasible and may offer some advantages in selected women.Copyright © 2022 Interdonato, Scollo, Bignardi, Massimello, Ferrara, Donatiello, Caretto, Mannella, Pecorino, Meroni and Simoncini.

Ioannis, G. and N. Raffaele (2022). "The use of AI in the surgical management of epithelial ovarian cancer: protocol for a systematic review."
	
Ioannis Pavlidis, T. (2023). The effect of metformin on bone mass of adolescent girls with polycystic ovary syndrome: Systematic review.
	Polycystic ovary syndrome (pcos) is the most common hormonal disorder in women of reproductive age. Hormonal disturbances seen in the syndrome have been implicated in negative effects on bone health. On the other hand, metformin used to treat pcos has been found to have protective properties. With adolescence being the key period of bone health formation, it is interesting to study the efficacy of metformin use in adolescent girls with pcos and in the effect of metformin on their bone mass. The purpose of this thesis is to carry out a systematic review of the international literature to investigate the effects of metformin on the bone mineral density of adolescent girls with pcos. The systematic review was conducted according to the prisma guidelines. The search for the review studies was done in the databases 'pubmed', 'scopus', 'cochrane central' and 'www.clinicaltrials.com'. The review included studies that assessed the bone mineral density of adolescent girls with pcos and met the selection criteria set. These studies were assessed using the Newcastle-Ottawa scale. The initial search after applying appropriate filter automation to exclude ineligible studies yielded 566 studies. The screening process based on the selection criteria defined yielded 4 studies that were included in the present review. None of the studies showed an effect of metformin on the bone mineral density of adolescent girls with pcos. Metformin treatment appears to reduce serum testosterone levels, while its effect on fasting insulin and glucose, high-density lipoprotein, and low-density lipoprotein is conflicting. This is the first systematic review investigating the effect of metformin on bone mineral density in adolescent girls with pcos. A key finding of this is the significant lack of literature in this area, which highlights the need for more studies that will investigate in depth whether the administration of metformin in this population could have positive benefits, as suggested by other studies.

Ionescu, O.-M., et al. (2023). "Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women." Life (Basel, Switzerland) 13(1).
	Polycystic ovary syndrome (PCOS) is a disorder with an unknown etiology that features a wide range of endocrine and metabolic abnormalities that hamper fertility. PCOS women experience difficulties getting pregnant, and if pregnant, they are prone to miscarriage, gestational diabetes, pregnancy-induced hypertension and preeclampsia, high fetal morbidity, and perinatal mortality. Insulin, the pancreatic hormone best known for its important role in glucose metabolism, has an underrated position in reproduction. PCOS women who have associated insulin resistance (with consequent hyperinsulinemia) have fertility issues and adverse pregnancy outcomes. Lowering the endogen insulin levels and insulin resistance appears to be a target to improve fertility and pregnancy outcomes in those women. Berberine is an alkaloid with a high concentration in various medicinal herbs that exhibits a hypoglycaemic effect alongside a broad range of other therapeutic activities. Its medical benefits may stand up for treating different conditions, including diabetes mellitus. So far, a small number of pharmacological/clinical trials available in the English language draw attention towards the good results of berberine's use in PCOS women with insulin resistance for improving fertility and pregnancy outcomes. Our study aims to uncover how berberine can counteract the negative effect of insulin resistance in PCOS women and improve fertility and pregnancy outcomes.

Irene, I., et al. (2023). "Efficiency of Sclerotherapy for the Management of Endometrioma: a Systematic Review and Meta-Analysis of clinical and fertility outcomes." PROSPERO International prospective register of systematic reviews.
	
Irene, P., et al. (2022). "Uterine Preservation Vs Hysterectomy in Uterine Prolapse Surgery: A Systematic Review and Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	
Isabela Godoy, M., et al. (2022). "Does the use of hormonal replacement therapy by postmenopausal women cause to weight gain? A sistematic review."
	
Isenmann, E., et al. (2023). "Resistance training alters body composition in middle-aged women depending on menopause - A 20-week control trial." BMC Women's Health 23(1): 526.
	Background: Resistance training (RT) is effective in counteracting the age- and menopause-related loss of muscle mass (MM) and strength in middle-aged women (40-60 years). Research on RT with free weights is limited in pre- and post-menopausal women. Based on this, a 20-week training intervention was conducted with this population to investigate the effects of systematic RT with free weights on strength capacity and body composition.; Method: Forty-one healthy women (52.0 ± 3.6 years) participated in this study. After 10-week control phase (no RT, T0-T1) followed by a 10-week intervention phase (T1-T2) with RT twice a week and 6-8 sets of each muscle per week. Subjects were randomly assigned to a low-intensity (50% 1-RM) or moderate-intensity (75% 1-RM) RT group and divided into pre-menopausal and post-menopausal according to their hormone profile. Fat-free mass (FFM), MM, fat mass (FM), muscle thickness (Vastus lateralis (VL), Rectus femoris (RF), Triceps brachii (TB)), grip strength, 1-RM squat and bench press were assessed before and after each phase. Statistical analysis was performed using a linear mixed model to account for fixed (time and group) and random (individual) effects.; Results: A total of 31 women successfully completed the study. No injuries occurred during the intervention. Significant increases in 1-RM squat and bench press were observed in all groups. No interaction effect was observed for the strength parameters. In pre-menopausal women, FFM, MM and RF muscle thickness increased significantly, while VL showed a trend. These effects were not present in post-menopausal women regardless of RT intensity.; Conclusion: RT with free weight is safe and effective for middle-aged women to increase 1-RM. Hypertrophy effects were found exclusively in pre-menopausal women. To achieve hypertrophy and/or body composition changes in post-menopausal women, larger training volumes (> 6-8 sets/muscle per week) are likely required. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ishchenko, A. A., et al. (2022). "Subtotal hysterectomy with deep excision of cervical mucosa as an alternative to total hysterectomy. Pros and cons." Voprosy Ginekologii, Akusherstva i Perinatologii 21(4): 69-76.
	Objective. A comparative analysis of the immediate and long-term outcomes of total and subtotal hysterectomy with excision of the mucosal and muscular layers of the cervix in patients with benign uterine diseases. Patients and methods. A total of 366 patients aged 41 to 57 years were examined. Patients were divided into two groups: the study group (n = 254), which included patients who underwent laparovaginal subtotal hysterectomy with excision of the cervical mucosal and muscular layers using a modified cutting instrument (surgical cutter), and the comparison group (n = 112), which included patients who underwent total hysterectomy. All operations were performed by a laparoscopic approach. The duration of postoperative outpatient follow-up was 1-48 months. Results. In 88.6% of patients in the study group, there were no pronounced vegetative-vascular and psycho-emotional disorders, exacerbation or worsening of chronic somatic diseases; 56.3% of patients in the comparison group had clinical manifestations of the post-hysterectomy syndrome. Deterioration in the quality of sexual life (reduced libido and/or anorgasmia) was observed in 9.4% and 36.6% of women in the study and comparison groups, respectively. Vaginal vault prolapse was revealed in 3.6% of patients in the comparison group and vaginal vault granulation - in 4.5% of patients 2-3 years after surgery. No similar complications were registered in the study group. Conclusion. Subtotal hysterectomy with excision of the cervical mucosal and muscular layers using the presented technique can serve as an alternative to total hysterectomy in patients with benign uterine pathology. Preservation of the uterine suspensory apparatus, innervation, and blood supply of the cervical stump and the upper third of the vagina reduces the risk of pelvic floor anatomical and functional disorders and minimizes the possibility of post-hysterectomy pelvic organ prolapse. The proposed method of hysterectomy helps to reduce the duration of surgery, blood loss, the risk of intra-and postoperative complications, to minimize the development of cervical stump diseases and improve patients' quality of life.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Ishchenko, A. A., et al. (2022). "Use of xenon anesthesia as an element of accelerated rehabilitation in pelvic organ prolapse surgery." Voprosy Ginekologii, Akusherstva i Perinatologii 21(5): 36-44.
	Objective. To analyze the efficacy and safety of surgical correction of pelvic organ prolapse under xenon anesthesia as the main fast-track protocol in comparison with standard perioperative management. Patients and methods. This study enrolled 66 patients aged 31 to 73 years with stages 2-4 pelvic organ prolapse (POP-Q). Two groups were identified: group 1 (study) consisted of 24 patients who underwent fast-track surgery; group 2 (control) included 42 patients who were treated according to standard perioperative management protocols. The following elements of accelerated rehabilitation were used in the study group: psychological training, reduced preoperative fasting time, unlimited fluid intake (last fluid intake 4 hours before surgery), no mechanical bowel preparation, use of xenon anesthesia, early enteral feeding in the postoperative period, maintenance of normovolemia, early mobilization of patients. Results. There were no complications in the early postoperative period in both patient groups. One recurrence of the disease in each group was diagnosed in the long-term period. The length of stay in group 1 was statistically significantly shorter than that in group 2: 2.0 versus 3-5 hospital days, respectively. Conclusion. Surgical correction of pelvic organ prolapse using elements of accelerated rehabilitation is an optimal and rational perioperative management approach in comparison with standard techniques.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Ishihara, O., et al. (2021). "Randomized, assessor-blind, antimüllerian hormone-stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with follitropin delta." Fertility and Sterility 115(6): 1478‐1486.
	Objective: To establish the relationship between follitropin delta doses (recombinant follicle‐stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimüllerian hormone (AMH) levels. Design: Randomized, controlled, assessor‐blind, AMH‐stratified (low 5.0–14.9 pmol/L; high 15.0–44.9 pmol/L) dose‐response trial. Setting: Reproductive medicine clinics. Patient(s): A total of 158 Japanese women (20–39 years of age). Intervention(s): Controlled ovarian stimulation with 6, 9, or 12 μg/d of follitropin delta or 150 IU/d follitropin beta as a reference arm in a gonadotropin‐releasing hormone antagonist cycle. Main Outcome Measure(s): Number of oocytes retrieved. Result(s): Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose‐relation was established, which also remained significant within each AMH strata. Significant dose‐responses also were observed for serum estradiol, inhibin A, and progesterone at end‐of‐stimulation with follitropin delta. The vital pregnancy rate per started cycle with follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum. Conclusion(s): This trial establishes the dose‐response relationship between follitropin delta and ovarian response in Japanese women. Clinical Trial Registration Number: NCT02309671.

Ishikawa, M., et al. (2021). "A randomized phase II/III trial of conventional paclitaxel and carboplatin with or without bevacizumab versus dose-dense paclitaxel and carboplatin with or without bevacizumab, in stage IVB, recurrent, or persistent cervical carcinoma (JCOG1311): Primary analysis." Gynecologic Oncology 162(2): 292-298.
	OBJECTIVE: To assess the efficacy and safety of dose-dense weekly paclitaxel plus carboplatin (ddTC) with or without bevacizumab compared to conventional, tri-weekly paclitaxel plus carboplatin (cTC) with or without bevacizumab, in metastatic or recurrent cervical carcinoma not amenable to curative local therapy. METHODS: Patients were randomly assigned to either the cTC or ddTC arm. The cTC regimen was paclitaxel 175 mg/m2 and carboplatin at an area under the curve (AUC) of 5 on day 1. The ddTC regimen was paclitaxel 80 mg/m2 on day 1, 8, 15 and carboplatin at AUC of 5 on day 1. Both cTC and ddTC treatments were repeated every 3 weeks for up to 9 cycles. After bevacizumab was approved in Japan, patients in both arms received bevacizumab 15 mg/kg if not contraindicated. The primary endpoint of phase II part was response rate (RR). If the RR of ddTC+bevacizumab was found to be at least 5% better than to cTC + bevacizumab, the study would proceed to phase III part, which had overall survival as its primary endpoint. CLINICAL TRIAL INFORMATION: jRCTs031180007. RESULTS: In total, 122 patients were randomly assigned to either the cTC arm (cTC + bevacizumab: 32; cTC:29) or the ddTC arm (ddTC+bevacizumab: 30; ddTC:31). The RR for patients on cTC + bevacizumab was 67.9%, and for patients on ddTC+bevacizumab 60.7%, cTC: 55.2%, and ddTC: 50.0%. CONCLUSIONS: The study did not meet the primary endpoint of phase II portion. Dose-dense, weekly paclitaxel plus carboplatin is not promising for metastatic or recurrent cervical carcinoma.

Ishizawa, C., et al. (2023). "Levonorgestrel-Releasing Intrauterine System Improves Menorrhagia-Related Quality of Life in Patients with Symptomatic Adenomyosis." Reproductive sciences (Thousand Oaks, Calif.) 30(3): 966-973.
	Levonorgestrel-releasing intrauterine system (LNG-IUS) relieves dysmenorrhea and heavy menstrual bleeding (HMB) in adenomyosis. However, its efficacy on health-related quality of life (HR-QOL) in patients with symptomatic adenomyosis remains unclear. The menorrhagia multi-attribute scale (MMAS), which measures HR-QOL improvement through the treatment of HMB, has never been used for evaluating menorrhagia-specific HR-QOL in patients with symptomatic adenomyosis. Hence, this study aimed to investigate the efficacy of LNG-IUS in improving menorrhagia-specific HR-QOL in these patients using the MMAS. The participants were diagnosed by magnetic resonance imaging. We also assessed the relationships between menorrhagia-specific HR-QOL, blood hemoglobin levels, and the degree of dysmenorrhea before and during LNG-IUS treatment. The LNG-IUS treatment improved the menorrhagia-specific HR-QOL more effectively in incipient type adenomyosis than in advanced type adenomyosis. The efficacy of LNG-IUS treatment on dysmenorrhea evaluated by the visual analog scale score tended to be better in the incipient type than in the advanced type. By the treatment of LNG-IUS, the blood hemoglobin level was not improved in the advanced type but in the incipient type. Furthermore, dysmenorrhea and HMB-related anemia were associated with HR-QOL impairment, and LNG-IUS treatment may improve the HR-QOL by relieving the symptoms. In conclusion, the effectiveness of LNG-IUS on HR-QOL is decreased by advanced adenomyosis. Thus, magnetic resonance imaging use should be reinforced to predict LNG-IUS efficacy in improving the HR-QOL of patients with adenomyosis. (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Islam Md, S., et al. (2023). "Targeting fibrotic signaling pathways by EGCG as a therapeutic strategy for uterine fibroids." Scientific Reports 13(1): 8492.
	Fibrosis is characterized by excessive accumulation of extracellular matrix, which is a key feature of uterine fibroids. Our prior research supports the tenet that inhibition of fibrotic processes may restrict fibroid growth. Epigallocatechin gallate (EGCG), a green tea compound with powerful antioxidant properties, is an investigational drug for uterine fibroids. An early phase clinical trial showed that EGCG was effective in reducing fibroid size and its associated symptoms; however, its mechanism of action(s) has not been completely elucidated. Here, we probed effects of EGCG on key signaling pathways involved in fibroid cell fibrosis. Viability of myometrial and fibroid cells was not greatly affected by EGCG treatment (1-200 µM). Cyclin D1, a protein involved in cell cycle progression, was increased in fibroid cells and was significantly reduced by EGCG. EGCG treatment significantly reduced mRNA or protein levels of key fibrotic proteins, including fibronectin (FN1), collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor (CTGF), and actin alpha 2, smooth muscle (ACTA2) in fibroid cells, suggesting antifibrotic effects. EGCG treatment altered the activation of YAP, β-catenin, JNK and AKT, but not Smad 2/3 signaling pathways involved in mediating fibrotic process. Finally, we conducted a comparative study to evaluate the ability of EGCG to regulate fibrosis with synthetic inhibitors. We observed that EGCG displayed greater efficacy than ICG-001 (β-catenin), SP600125 (JNK) and MK-2206 (AKT) inhibitors, and its effects were equivalent to verteporfin (YAP) or SB525334 (Smad) for regulating expression of key fibrotic mediators. These data indicate that EGCG exhibits anti-fibrotic effects in fibroid cells. These results provide insight into mechanisms behind the observed clinical efficacy of EGCG against uterine fibroids. (© 2023. The Author(s).)

Islam, N., et al. (2021). "Prophylactic antibiotics for preventing genital tract infection in women undergoing surgical procedures for incomplete abortion: a systematic review and meta-analysis of randomised controlled trials." BJOG : an international journal of obstetrics and gynaecology 128(8): 1273-1281.
	Background: Findings about the effect of prophylactic antibiotics in preventing genital tract infection (GTI) associated with surgical procedures used for incomplete abortions are conflicting. Some reported a decrease in infection associated with the use of antibiotic prophylaxis, whereas others found no significant reduction in GTI.; Objective: To synthesise systematically the evidence on the effect of prophylactic antibiotics compared with placebo in women undergoing surgical procedures for incomplete abortion.; Search Strategy: In February 2020, PubMed, Embase and Cochrane Central for Register of Controlled Trials were searched for relevant published randomised controlled trials.; Selection Criteria: Randomised controlled trials reporting GTI following surgical procedures for incomplete abortion and comparing antibiotic prophylaxis with placebo.; Data Collection and Analysis: Meta-analysis using inverse variance heterogeneity model included subgroup and sensitivity analyses determined a priori were conducted. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).; Main Results: A total of 16 178 women who participated in 24 eligible randomised controlled trials published between 1975 and 2019 were included. Pooled estimates showed the risk of GTI following surgical procedures after incomplete abortion was significantly lower among those who had prophylactic antibiotics (relative risk [RR] = 0.72; 95% CI 0.58-0.90; I 2 = 49%). There was no significant effect of antibiotics in women in low- and middle-income countries (three studies, 3579 participants, RR = 0.90; 95% CI 0.50-1.62; I 2 = 63%), but it was clinically and statistically significant among women high-income countries (21 studies, 12 599 participants, RR = 0.67; 95% CI 0.53-0.84; I 2 = 44%), with a strong level of evidence as assessed by GRADE.; Conclusion: This study provides evidence that antibiotic prophylaxis is beneficial in reducing post-abortion GTI among women undergoing surgical procedures for incomplete abortion. More studies are needed from low- and middle-income countries.; Tweetable Abstract: Prophylactic antibiotics after incomplete abortion are effective in reducing GTI. More studies are needed from low- and middle-income countries. (© 2020 John Wiley & Sons Ltd.)

Islands University of the, B., et al. (2023). Tele-rehabilitation for Female Athletes With Pelvic Floor Dysfunctions.
	No Results Available Behavioral: Pelvic floor muscle training with biofeedback device|Behavioral: Pelvic floor muscle training|Behavioral: Information about pelvic floor and communication with health professionals Functional characteristics of pelvic floor musculature with perineometer|Anatomical characteristics of pelvic floor structures with ultrasound I|Anatomical characteristics of pelvic floor structures with ultrasound II|Anatomical characteristics of pelvic floor structures with ultrasound III|Sports performance through maximal vertical jump|Presence of pelvic floor disorders symptomatology|Frequency of pelvic floor disorders symptomatology|Sexual dysfunction symptomatology|Level of quality of life|Engagement to training program Female Not Applicable 45 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment 124CER19_ November 20, 2023

Ismail, N. H., et al. (2021). "Augmentation of the Female Reproductive System Using Honey: A Mini Systematic Review." Molecules (Basel, Switzerland) 26(3).
	Phytochemical contents of honey are presumed to be beneficial to the female reproductive system (FRS). However, the biological effects of honey supplementation (HS) in vivo on the FRS remain unclear. This review aims to investigate the current literature on the effects of HS on the FRS, particularly on the sex hormone profile and reproductive organs (uterus and vagina). A systematic literature search using Scopus, MEDLINE via Ovid and Cochrane Library databases was conducted. Records were screened and identified for preclinical and clinical studies addressing the effects of HS on the FRS. Data on populations, interventions, outcomes and methodological quality were extracted. Studies were synthesised using tables and written summaries. Of the 198 identified records, six fulfilled the inclusion criteria. All six records were used for data extraction: two experimental studies using rats as the model organism and four human clinical studies of honey on female reproductive health. HS elevated the progesterone levels, restrained body weight increase, prevented uterine and vaginal atrophies in ovariectomised rats, attenuated symptoms of candidiasis and improved oxidative status in patients. Current evidence shows that short-term HS following surgical or physiological menopause exerts an oestrogenic, antioxidant and anti-inflammatory effect on the FRS. However, insufficient long-term studies preclude any definitive conclusions.

Isokaanta, S., et al. (2022). "Resilience, pain, and health-related quality of life in gynecological patients undergoing surgery for benign and malignant conditions: a 12-month follow-up study." BMC Women's Health 22(1): 345.
	Background: Gynecological surgery has many impacts on women's physical and mental health, and efforts to improve recovery from surgery are constantly under evaluation. Resilience is an ability to overcome stressors and adversities, such as traumas and surgeries. This study aimed to explore patients' resilience and psychological symptoms in relation to recovery, health-related quality of life (HRQoL), and pain one year after gynecological surgery. Method(s): In a prospective cohort study, we enrolled consecutive elective gynecologic surgery patients who completed questionnaires before and at one year after surgery: the Resilience Scale-25, the 15D instrument of HRQoL (15D), the Life Satisfaction Scale-4, and the Hospital Anxiety and Depression Scale. Their mean 15D scores were compared to those of an age-matched sample of women from the general Finnish population (n = 2743). Result(s): We enrolled 271 women who underwent gynecological surgery due to benign (n = 190) and malignant (n = 81) diagnoses. Resilience was equally high in women with benign and malignant diagnoses at both time points. Higher resilience associated with less pain, analgesic use, and better pain relief from the use of pain medication at 12 months after surgery. Pain intensity was similar in the two groups, but patients with benign diseases had less pain at 12 months than before surgery. Before surgery, patients' HRQoL was worse than that of the general population, but at 12 months the mean HRQoL of patients with benign diseases had improved to the same level as that in the general population but had decreased further in patients with malignant diseases. Anxiety was higher and life satisfaction was lower in patients with malignant diseases before surgery. At 12 months, anxiety had decreased in both groups, and life satisfaction had increased in patients with malignant diseases. Depression was similarly low in both groups and time points. Conclusion(s): Resilience correlated with less pain one year after surgery. After surgery, HRQoL improved in patients with benign diseases but deteriorated in patients with malignant diseases. Patients with low resilience should be identified during preoperative evaluation, and health care professionals should give these patients psychological support to enhance their resilience. Trial Registration ClinicalTrials.gov; registered October 29, 2019; identifier: NCT04142203; retrospectively registered.Copyright © 2022, The Author(s).

Israfil-Bayli, F., et al. (2021). "C-STICH: cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes-a multicentre randomised controlled trial." Trials 22(1): 664.
	Background: Preterm birth is associated with significant mortality and morbidity for mothers and babies. Women are identified as high risk for preterm birth based on either previous medical/pregnancy history or on ultrasound assessment of the cervix. Women identified as high risk can be offered a cervical cerclage (a purse string stitch) around the cervix (neck of the womb) to reduce the risk of preterm birth. In women who have a cervical cerclage, the procedure can be performed using either a monofilament (single‐stranded) or braided (woven) suture material. Both suture materials are routinely used for cervical cerclage and there is uncertainty as to which is superior. Methods: A multicentre, open, randomised controlled superiority trial of 2050 women presenting at obstetric units, deemed to be at risk of preterm birth and already scheduled to have a cervical cerclage as part of their standard care. Inclusion criteria include singleton pregnancies and an indication for cervical cerclage for either a history of three or more previous mid‐trimester losses or premature births (≤ 28 weeks), insertion of cervical sutures in previous pregnancies, a history of mid trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix, or women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan. Exclusion criteria include women who have taken part in C‐STICH previously, are aged less than 18 years old at the time of presentation, require a rescue cerclage, and are unwilling or unable to give informed consent and in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route). Following informed consent, women are randomised on a 1:1 basis to either monofilament or braided suture, by minimisation. The primary outcome is pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life), and secondary outcomes include the core outcome set for preterm birth trials. Discussion: Optimising established interventions to prevent preterm birth is important in reducing perinatal mortality rates. Trial registration: ISRCTN 15373349. Registered before recruitment on 03 December 2014 prior to first recruit.

Isrctn (2021). "A clinical study to assess the efficacy of a probiotic supplement for women to reduce depression and anxiety symptoms after giving birth." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: 2 groups of 100 subjects were invited to orally take one capsule/day for 90 days, starting from delivery, as follows: one group (A) used the complete active treatment (Probiotics mix + multivitamin food supplement), one group (B) used the reference treatment (multivitamin food supplement). A restricted randomization list is generated by the site Study Coordinator using an appropriate statistic algorithm (“Wey’s urn”). CONDITION: Improvement of post‐partum depression and mastitis in healthy new mothers and reduction of excessive crying in the newborns. ; Mental and Behavioural Disorders PRIMARY OUTCOME: Depression and anxiety symptoms and post‐natal stress measured using the Edinburgh Postnatal Depression Scale (EPDS) after 45 and 90 days SECONDARY OUTCOME: ; 1. Baby's crying, measured using Breastfeeding Self Efficacy Scale Short Form and Children Cry Questionnaires after 45 and 90 days.; 2. Mastitis measured using Breastfeeding Quality Questionnaire after 45 and 90 days; INCLUSION CRITERIA: Healthy pregnant female subjects after their delivery

Isrctn (2021). "Testing an internet intervention for preventing and reducing perinatal depressive symptoms and promoting subjective well-being." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The overall aim of the current project is to test the effectiveness, cost‐effectiveness and implementation of Mamma Mia with guidance compared to unguided Mamma Mia and usual care. As the effectiveness of unguided Mamma Mia compared to usual care has already been evaluated in an existing trial, the study will be a two‐armed cluster‐randomized hybrid trial. Using Optimal Design v3.01, min. 14 and max. 24 well‐baby clinics will be randomized to either Mamma Mia or Mamma Mia with guidance. To ensure implementation, the researchers calculate a min/max 3/5 midwives/health nurses per health station. It is based on a cluster size of 15 women per health center. It gives =80% probability to detect a standardized effect size of 0.50 which corresponds to an average group difference divided by the standard deviation for the outcome measure. The prerequisites are based on an intra‐cluster correlation coefficient of 0.01, as observed in previous cluster studies on pregnancy and postpartum depression, six measurements, an alpha level of 5% (p‐value <0.05) and a minimum of 14 health stations. The estimated number of women will therefore be min. 210 and max. 360. Adjusted for a dropout rate of 37% as observed in the first Mamma Mia study, the total sample size is between 334 and 572 participants with a 1: 1 distribution of participants between the groups. Methods and procedures Well‐baby clinics will be randomly allocated to the two treatment groups. Pregnant women will be recruited prior to gestational week (GW) 26 during routine consultations using an online registration form. Surveys will be completed electronically at baseline; GW 21‐26, GW 37, 1.5, 3, 6 and 12 months postpartum. Automatically generated log data wil CONDITION: Perinatal depressive symptoms and subjective well‐being ; Mental and Behavioural Disorders PRIMARY OUTCOME: ; 1. Depression measured using the Edinburgh Postnatal Depression Scale at baseline (approx. gestational week 25) at gestational week 37 and 1.5, 3, 6, and 12 months postpartum; 2. Subjective well‐being measured using the Satisfaction with Life Scale and the Positive and Negative Affect Scale at baseline (approx. gestational week 25), gestational week 37, and 1.5, 3, 6, and 12 months postpartum; 3. Anxiety measured by the acute anxiety and adjustment subscale of the perinatal anxiety screening scale at baseline (approx. gestational week 25), gestational week 37, and 1.5, 3, 6, and 12 months postpartum; ; Implementation primary outcomes:; 1. Acceptability, appropriateness and feasibility respectively measured using the Acceptability of Intervention Measure, the Intervention Appropriateness Measure and the Feasibility of Intervention Measure at approx. 3 and 15 months after training and initial instructional meetings; 2. Systems and capacity changes measured using the Systems and Capacity Changes –Section D at approx. 3 and 15 months after training and initial instructional meetings; 3. Working alliance measured using Working Alliance Inventory–Short Revised at approx. 3 and 15 months after training and initial instructional meetings; 4. Implementation outcomes measured using the Implementation Components Questionnaire–Implementation Outcomes at approx. 3 and 15 months after training and initial instructional meetings; SECONDARY OUTCOME: ; 1. Health‐related quality of life score measured by 5‐Level EuroQoL‐5D at baseline (approx. gestational week 25), gestational week 37, and 1.5, 3, 6, and 12 months postpartum; 2. Relationship satisfaction measured using Relationship Satisfaction (RS) at baseline, 6 weeks postpartum, and 6 and 12 months postpartum; 3. Self‐efficacy measured using Coping Self‐Efficacy (SE) at baseline; 4. Attachment measured using Prenatal Attachment Inventory at baseline and gestational week 37; 5. Stress measured using Perceived Stress Scale at baseline, 1.5, 6, and 12 months postpartum; 6. Breastfeeding self‐efficacy measured using the Breastfeeding Self‐Efficacy Scale at 1.5, 3, 6, and 12 months postpartum; 7. Social support m sured using Berlin Social Support Scales at baseline, gestational week 37, and 1.5, 3, 6, and 12 months postpartum; 8. Emotion regulation measured using the Emotion Regulation Questionnaire at baseline, 1.5, 6, and 12 months postpartum; 9. Sleep measured using the Brief Infant Sleep Questionnaire at 1.5, 3, 6, and 12 months postpartum; 10. Infant socio‐emotional development measured using Ages & Stages Questionnaire: Socio‐Emotional at 1.5, 3, 6, and 12 months postpartum; ; Implementation secondary outcome measures:; 1. Adherence to the guidelines for the implementation and the clinical work in the blended intervention group, measured using an Adherence checklist that will be completed by health personnel after all consultations for all the postpartum women who receive guidance in using Mamma Mia; 2. Log data recorded continuously throughout the Mamma Mia program; 3. The implementation process will be explored at focus groups completed with health personnel at one timepoint during the project period; 4. The plan for implementation will be completed by health personnel in the blended intervention following training and before recruitment of pregnant women; 5. SWOT interview (strength, weaknesses, opportunities, threats) completed with perinatal women (approx. after when they have completed the Mamma Mia program) at one timepoint during the project period; INCLUSION CRITERIA: 1. Pregnant women aged 18 years and over 2. Up until 26 gestational weeks 3. Provide a valid e‐mail address 4. Read and understand Norwegian at a high‐school level

Isrctn (2022). "Clinical studies to examine the effects of intranasal kisspeptin delivery on reproductive hormones." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Randomised, placebo‐controlled, cross‐over study in healthy volunteers (men and women) and patients with common reproductive disorders (including hypothalamic amenorrhoea). Following self‐administration of intranasal kisspeptin (dose range 3.2 to 25.6 nmol/kg) or placebo using a nasal spray device, serum reproductive hormones are measured every 15 minutes for 4 hours. Study visits will be at least 1 week apart to ensure washout, with the order of the interventions randomised (using https://www.randomizer.org). CONDITION: Reproductive disorders ; Nutritional, Metabolic, Endocrine PRIMARY OUTCOME: Blood levels of reproductive hormones (kisspeptin, luteinizing hormone, follicle stimulating hormone, testosterone [men] and oestradiol/progesterone [women]) measured using automated chemiluminescent immunoassays at baseline and every 15 minutes for 4 hours SECONDARY OUTCOME: ; 1. Safety monitoring: heart rate, blood pressure, and the presence of adverse symptoms measured using automated blood pressure monitor every 15 minutes for 4 hours; 2. Behavioural parameters of reproductive behaviour assessed using validated psychometric questionnaires (including the Sexual Arousal and Desire Inventory, Positive and Negative Affect Schedule, and State‐Trait‐Anxiety‐Inventory) at baseline and every hour until 4 hours; INCLUSION CRITERIA: Healthy volunteers: 1. Aged 18–70 years 2. Non‐smokers 3. Free of current or past physical or psychiatric illness 4. Naive to psychoactive substances, prescribed or illicit, for a minimum of 6 months prior to screening. 5. Regular menstrual cycles (women) For patients with common reproductive disorders: 1. Patients diagnosed in accordance with established guidelines (e.g. Endocrine Society guidelines for hypothalamic amenorrhoea)

Isrctn (2022). "Community singing interventions for postnatal depression." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Melodies for Mums will be a randomised clinical trial in which postnatally depressed women and their infants will randomly be assigned to 10 weeks of singing sessions or 10 weeks of usual community‐based activities. Mother‐infant dyads will partake in the trial for a total of 36 weeks, the first 10 of which will be the intervention period, and the remainder of which will be a follow‐up period. More specifically, dyads will be assessed for demographic, psychological, social, and biological information either by KCL researchers or asked to complete online questionnaires at baseline (before the start of the intervention period), at week 6, at week 10, at week 20, and at week 36. Furthermore, qualitative data will be collected after week 10 (end of the intervention period) from focus groups and small‐group interviews with a small subset of participants. Finally, Implementation Science data regarding the implementation and cost‐effectiveness of the singing intervention will be collected from mothers and stakeholders using questionnaires, surveys, interviews and other data collection methods. The end of the trial for a participant will be after the 36‐week follow‐up or withdrawal from the study. Control groups are non‐musical free community mother and baby activities that will be available in the same geographical area as the venues where the singing sessions will take place or provided online by the same venues/organisations as they would if they were being delivered in person. The overarching aim of the study is to evaluate both the clinical and implementation effectiveness of community singing for women (and their infants) on their symptoms of postnatal depression. More specifically, the aim of the clinical effectiveness com CONDITION: Postnatal depression ; Mental and Behavioural Disorders PRIMARY OUTCOME: ; 1. The effectiveness of group singing interventions on symptoms of postnatal depression measured using the Edinburgh Postnatal Depression Scale (EPDS) at baseline and Week 10 (end of treatment); 2. The acceptability of the intervention measured using the Acceptability of Intervention Measure (AIM) at week 10 (end of treatment); SECONDARY OUTCOME: ; 1. Depression measured using the Hamilton Depression Rating Scale (HDRS) at baseline and weeks 6, 10, 20 and 36; 2. Depression measured using the Beck Depression Inventory (BDI) at baseline and weeks 6, 10, 20 and 36; 3. Stress measured using the Perceived Stress Scale (PSS) at baseline and weeks 6, 10, 20 and 36; 4. Wellbeing measured using the Office for National Statistics Wellbeing Scale (ONS) at baseline and weeks 6, 10, 20 and 36; 5. Anxiety measured using the State‐Trait Anxiety Scale (STAI) at baseline and weeks 6, 10, 20 and 36; 6. Observed mother‐infant interaction assessed using the Crittenden CARE‐Inde X(CCI) at baseline and weeks 10 and 36; 7. Perceived mother‐infant relationship assessed using the Maternal Postpartum Attachment Scale (MPAS) at baseline and weeks 6, 10, 20 and 36; 8. Perceived mother‐infant relationship assessed using the Parent Reflective Functioning Questionnaire (PRFQ) at baseline and weeks 6, 10, 20 and 36; 9. Social support and reduces loneliness assessed using the UCLA Loneliness Scale at baseline and weeks 6, 10, 20 and 36; 10. Social support and reduces loneliness assessed using the Multidimensional Scale of Perceived Social Support (MSPSS) at baseline and weeks 6, 10, 20 and 36; 11. Stress hormones, including hair cortisol, diurnal cortisol and salivary cytokines, analysed using an array of techniques including enzyme‐linked immunosorbent assay (ELISA) at week 1 and weeks 6 and 10; 12. Levels of salivary oxytocin analysed using an array of techniques including enzyme‐linked immunosorbent assay (ELISA) at week 1 and weeks 6 and 10; 13. Lived experience of mothers with PND assessed using focus groups immediately following session 10 (if logistically possible) for all mothers focusing on their lived experience of the intervention and their reported mechanisms of effect; 14. The phenomenolo of PND and how singing intersects with PND among women with particular risk factors for PND (traumatic birth, adverse childhood experiences, and social isolation/loneliness) assessed using semi‐structured interviews with three sub‐groups of women self‐reporting particular risk factors for PND: traumatic birth, adverse childhood experiences, and social isolation/loneliness, at week 10 (end of intervention); 15. The acceptability of the intervention assessed using the Intervention Measure (AIM) at week 10 (end of intervention); 16. Reasons for perceived acceptability of the intervention assessed using semi‐structured interviews at week 10 (end of intervention); 17. Uptake/reach of the intervention assessed using recruitment rate records (number of eligible women who sign up to the intervention) at week 10 (end of intervention); 18. The appropriateness of the intervention assessed using Intervention Appropriateness Measure (IAM) at week 10 (end of intervention); 19. The appropriateness of the intervention assessed using semi‐structured interviews at week 10 (end of intervention); 20. The feasibility of the intervention assessed using the Feasibility of Intervention Measure (FIM) at week 10 (end of intervention); 21. The feasibility of the intervention assessed using semi‐structured interviews at week 10 (end of intervention); 22. Intervention adherence and attrition rates assessed using attendance data (rates and dropout reasons) at week 10 (end of intervention); 23. The adoption of the intervention assessed using participants and stakeholder enrollment rates at week 10 (end of intervention); 24. The cost‐effectiveness of the intervention assessed using the 5‐level EQ‐5D version (EQ5D‐5L) at week 10 (end of intervention); 25. The cost‐effectiveness of the intervention assessed using the Adult Service Use Schedule (AD‐SUS) at week 10 (end of intervention); 26. The cost‐effectiveness of the intervention assessed using implementation activity logs (to estimate implementation costs) at week 10 (end of intervention); 27. Factors affecting the sustainability and scalability of the intervention assessed using the NOMAD Scale at week 10 (end of intervention); 28. Factors affecting the sustainability and scalability of the intervention assessed using semi‐structured interviews at week 10 (end of intervention); INCLUSION CRITERIA: 1. Women aged 18 years or older 2. Satisfactory understanding of English 3. Women who have a child between 0 and up to 9 months old 4. Women with postnatal depression diagnosed using symptoms of PND at a minimum score of 10 on the Edinburgh Postnatal Depression Scale (EPDS) 5. Access to an internet‐connected device (mobile phone, tablet, computer or laptop) to allow completion of assessments and participation in the singing sessions

Isrctn (2022). "The effect of screen time on nighttime urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: 1. After a diagnosis of primary monosymptomatic nocturnal enuresis, classified as mild (1‐2 wet nights/week), moderate (3‐5 wet nights/week) and severe (6‐7 wet nights/week), patients were separated by the amount of screen time: Group 1. < 120 min mean screen time/day Group 2. > 120 min mean screen time/day 2. For treatment response, patients were randomly assigned to treatment: Group 3. Patients were administered 120 µg desmopressin melt (DeM) and, in addition to supportive treatment, were requested to reduce daily screen time to < 60 mins Group 4. Patients were given 120 µg DeM and supportive treatment was recommended with no restriction of screen time 3. Patients who reduced their screen time to less than 60 minutes were followed for 3 months. 4. Patients without recurrence, defined by one or more night‐time bed wetting events in month 4, received further recommendations and terminated the trial. 5. Patients with recurrence were re‐evaluated and treatment was planned. Treatment of other patients who did not benefit from treatment and behavioral adjustments continued. 6. The groups were statistically compared in respect of descriptive data, response to treatment, and recurrence. CONDITION: Primary monosymptomatic enuresis ; Urological and Genital Diseases PRIMARY OUTCOME: Treatment response measured by the dryness of a child’s sleeping quarters recorded daily on waking, defined as a full response at 100% dryness, a partial response at 50‐99% dryness, or a failure at <50% dryness at month 3. Patients in groups 3 and 4 with a full response had their DeM treatment terminated and recurrence, defined by one or more night‐time bed wetting events in month 4, was determined at a follow‐up visit at the end of month 4. SECONDARY OUTCOME: Late recurrence, defined by one or more night‐time bed wetting events from month 4 and measured daily on waking, was recorded at a 6‐month long‐term follow‐up visit. INCLUSION CRITERIA: 1. Aged 6 to 18 years 2. Diagnosed as primary monosymptomatic enuresis nocturna as a result of history, physical examination and routine tests 3. Have not had an operation due to urinary system pathologies before 4. A body mass index below the 95th percentile 5. Screen exposure of different durations 6. Caregivers or patients who can keep a voiding diary, nighttime bedwetting chart

Isrctn (2022). "Evaluating ulipristal acetate and misoprostol for induced abortion through 63 days of pregnancy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Phase 1 of the research will compare two medication regimens with ulipristal acetate and misoprostol: 60 mg UPA orally + 800 mcg misoprostol buccally versus 90 mg UPA orally + 800 mcg misoprostol buccally. Participants will be randomized to the study groups based on a computer‐generated assignment. Phase 2 of the research will continue to evaluate the regimen that demonstrated the best outcomes in Phase 1. CONDITION: Induced abortion ; Pregnancy and Childbirth PRIMARY OUTCOME: Adverse events (complications) measured using self‐reporting at any point prior to discharge from the study SECONDARY OUTCOME: ; 1. Side effects measured using self‐reporting 1 hour after ulipristal administration and at the 1‐week follow‐up visit; 2. Efficacy measured using a clinical assessment of pregnancy viability at the 1‐week follow up; 3. Acceptability to participants of study medication measured using self‐reporting at discharge from the study; 4. Pain measured using a scale from 0‐10 one hour after ulipristal administration and at the 1‐week follow‐up visit; INCLUSION CRITERIA: 1. Pregnant with estimated gestational age = 63 days by ultrasound and desiring an abortion 2. Body mass inde X(BMI) = 32 kg/m2 3. Aged =18 years old or emancipated minor 4. With access to a telephone for follow‐up communication 5. Resident of Mexico City 6. Able to provide informed consent

Isrctn (2022). "Evaluation of the SENS-U as an alarm intervention in the treatment of children with daytime urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Participants will be divided into 3 arms in a 1:1:1 fashion: 1. Urotherapy only (control group) 2. Urotherapy + SENS‐U 3. Urotherapy + Sham‐device (placebo) Urotherapy will be given for 3 months. Children who are placed in the SENS‐U or Sham‐device arm will wear the device for 3 consecutive weeks during the 3 months of urotherapy treatment. The SHAM‐device has the exact same appearance as the SENS‐U. However, it does not measure the filling state of the bladder. The SHAM‐device is programmed to give an alarm at set time intervals. The device can best be compared to alarm interventions such as the timer watch. Outcome parameters will be measured at baseline, after the end of 3‐weeks intensive training with diary, after 3 months, and at 6 months after starting training. CONDITION: Treatment of children with functional daytime urinary incontinence ; Not Applicable PRIMARY OUTCOME: Number of 'wetting accidents' per week measured by questionnaires at baseline and 3 months SECONDARY OUTCOME: ; 1. Subjective improvement of LUTS according to parents using questionnaires at baseline, 3, and 6 months; 2. Change in urinary incontinence during follow‐up measured using the number of wetting accidents per week at 6 months; 3. Change in frequency voiding chart parameters (average, minimum, maximum void volumes corrected for bladder capacity for age (EBC) measured using voiding charts at baseline, 3, and 6 months; 4. Change in Quality of Life measured using questionnaires at baseline, 3, and 6 months; 5. Cost‐effectiveness measured using questionnaires set out to costs at 6 months; 6. Magnitude of the placebo‐effect measured using number of wetting accidents per week at baseline and 3 months; INCLUSION CRITERIA: 1. Aged between 6 and 15 years 2. Functional daytime urinary incontinence 3. Diagnosed with overactive bladder, dysfunctional voiding, or underactive bladder according to ICCS criteria 4. Eligible for urotherapy

Isrctn (2022). "Homocysteine levels in polycystic ovary syndrome (PCOS) patients." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Patients providing informed consent are randomized for treatment or no treatment. Randomization is based on a computer‐generated randomization list comprising 12 blocks of 4 positions each, total 48 positions. The positions are assigned on a strict chronological order. PCOS patients randomized to the study group were given two cycles of 200 mg Betaine, 200 mg L‐cystine, 16mg Niacin, 10 mg Zinc, 1.4 mg Vitamin B6, 1.4 mg Riboflavin, 400 mcg Folic acid (5MTHF – glucosamine), 2.5 mcg Vitamin B12 (methylcobalamin) preceding IVF cycle. The treatment, at the dose of one tab per day, is to be taken during 2 months before the planned follicular stimulation and thereafter during the stimulation. CONDITION: Improving the metabolic competence in oocytes of PCOS patients undergoing IVF treatment. ; Pregnancy and Childbirth PRIMARY OUTCOME: Clinical pregnancy, calculated as number of fetuses with heart activity beyond 20 weeks of gestation per transferred embryo SECONDARY OUTCOME: ; 1. FSH consumption during stimulation, calculated as cumulative number if FSH units injected; 2. Fertilization rate, calculated as the rate of fertilized oocytes (2 PN) out of the total number of inseminated oocytes; 3. Blastocyst rate, calculated as the rate of fertilized oocytes reaching the blastocyst stage at 5‐6 days; 4. Biochemical pregnancy, calculated as the rate of positive hCG at 7 days post embryo transfer out of the number of patients receiving an embryo transfer; INCLUSION CRITERIA: 1. PCOS patients diagnosed using Rotterdam's Criteria 2. Primary infertility for at least 1 year 3. No other condition leading to infertility

Isrctn (2022). "A trial evaluating active outpatient management to prevent hospital admission in women having fertility treatment who develop ovarian hyperstimulation syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Design: A randomised controlled trial (RCT) to assess the clinical and cost‐effectiveness, safety profile and acceptability of outpatient paracentesis compared to conventional conservative management (usual care) of women with moderate or severe OHSS Hypothesis: The use of outpatient paracentesis (OP) in the management of moderate or severe OHSS will result in earlier resolution of symptoms and avoid the need for hospital admission, when compared with usual care. Recruitment: This RCT will recruit women with early or late moderate or severe OHSS from approximately 20 NHS and private fertility units across England and Scotland. Women with a diagnosis of moderate or severe OHSS who meet the inclusion criteria will be randomly allocated (1:1) to either the treatment arm (where they will receive outpatient paracentesis and increased monitoring) or the control arm (where they will receive conservative management, which at most sites is usual care). A ‘conservative management’ (usual care) control arm has been selected in order to ascertain if outpatient paracentesis and increased monitoring is more effective than ‘conservative management’ (usual care) at reducing hospitalisations. Following ethical approval, the research will be undertaken as detailed below. 1. Local site confirmation of capacity and capability and site set‐up 2. Participant recruitment, baseline data collection, randomisation and intervention delivery will begin. 3. An internal pilot will take place for the first 15 months of recruitment. This internal pilot will assess the feasibility aspects relating to rates of recruitment, re CONDITION: Ovarian hyperstimulation syndrome ; Pregnancy and Childbirth PRIMARY OUTCOME: OHSS‐related hospitalisation for at least 24 hours measured using data collected by staff at fertility units by contacting the participant by telephone during monitoring, at patient visits within 28 days of randomisation or collected from hospital notes after 28 days INCLUSION CRITERIA: 1. Women presenting with moderate or severe, early or late OHSS as defined by the trial (see trial protocol for full definitions) 2. Patients able and willing to attend weekly follow‐up appointments in person or remotely, daily remote appointments/phone calls, and able to undertake self‐monitoring at home SECONDARY OUTCOME: ; 1. Need for hospitalisation (OHSS related) measured using data collected during symptom deterioration visits or other routes of hospitalisation, including clinical data and reasons stated for hospitalisation within 28 days of randomisation – independent blinded central assessment; 2. Time to resolution of OHSS measured using normalisation of the haematocrit and haemoglobin concentrations, normalisation of fluid input and output (no longer in a positive fluid balance), decrease in weight, and decrease in abdominal girth within 28 days of randomisation; 3. Progression of OHSS severity measured using the following criteria:; 3.1. Progression criteria from moderate to severe indicated by fluid accumulation in abdomen which becomes clinical ascites/clinically detectable with or with hydrothorax, with any of the following additional symptoms:; 3.1.1. Clinical ascites (± hydrothorax); 3.1.2. Oliguria (< 300 ml/day or <30 ml/hour); 3.1.3. Haematocrit >0.45; 3.1.4. Hyponatraemia (sodium <135 mmol/l); 3.1.5. Hypo‐osmolality (osmolality <282 mOsm/kg); 3.1.6. Hyperkalaemia (potassium >5 mmol/l); 3.1.7. Hypoproteinaemia (serum albumin <35 g/l); 3.1.8. Ovarian size usually >12 cm; 3.2. Progression criteria from severe to critical indicated by evidence of any one of the following features:; 3.2.1. Participant has a large hydrothorax; 3.2.2. Increasing haematocrit levels to >0.55; 3.2.3. A white cell count of over 25000/ml (confirmed via FBC test); 3.2.4. Change from oliguria (low urine output) to anuria (very little/no urine) (<100 ml/day); 3.2.5. Thromboembolism; 3.2.6. Acute respiratory distress syndrome; within 28 days of randomisation; 4. Live birth, pregnancy outcomes, neonatal death and serious adverse even including congenital abnormalities in the newborn measured using medical notes within 13.5 months of randomisation; 5. The occurrence of thrombosis or embolism and significant infections requiring antibiotic treatment or hospitalisation measured using medical notes within 90 days of randomisation; 6. Adverse events measured using medical notes, during a follow‐up, during contact with the participant, or during site monitoring within 28 days of randomisation. Specified adverse events will be identified through review of medical notes at 90 days and 13.5 months post randomisation; 7. Patient satisfaction assessed using the Client Satisfaction Questionnaire 8 (CSQ‐8) based on total scores at 28 days post‐randomisation; 8. Quality of life measured using EQ‐5D‐5L daily and at 28 days post‐randomisation;

Isrctn (2023). "AADAPT Online – Addressing young mums’ and dads’ low mood and their parenting." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Participants will be randomised in a 1:1 ratio to (i) AADAPT Online Intervention or (ii) AADAPT Self‐Guided (waitlist control). Randomisation will be minimised by severity of depression (EPDS scores <=13; >=14) and the age of the parent (<=20; >=21). Participants will be randomised using a secured web‐based called Trial Deck that will automatically occur after the participating parent completes the consent and baseline measures. Intervention(s): Online psychological intervention for parents with depression supported by peer mentors (AADAPT Online). AADAPT Online is a behavioural activation and parenting self‐help package supported by peer mentors (referred to as Parent Buddies). The seven modules are completed by the parent over 7 weeks supported by weekly 15‐20 minute conversations (either via messaging or audio/video call) between the adolescent parent and the Parent Buddy. Comparator: Waitlist control group who receive the AADAPT Online materials (but no support from peer mentors) via email or post after their follow‐up assessment. For both arms (intervention and wait list), there is a follow‐up assessment 12 weeks after randomisation. Study information will be available online. After eligibility screening which involves questions online and a brief phone call with the research team, participants will be automatically randomised to receive either AADAPT Online or to the wait‐list control after consenting online and completing some baseline measures. Treatment allocation will be communicated to participants online. CONDITION: Depression in parents aged 16‐24 years ; Mental and Behavioural Disorders PRIMARY OUTCOME: Parental depression is measured using parent self‐report questionnaire (Edinburgh Postnatal Depression Scale, EPDS) at baseline and 12 weeks post randomisation SECONDARY OUTCOME: 1. Parent‐infant interactions assessed from simultaneous Headcam footage from parent and infant collected at baseline and 12 weeks post‐randomisation; 2. Parental stress measured using parent self‐report questionnaire (Parenting Stress Index, PSI‐4‐SF) at baseline and 12 weeks post‐randomisation; 3. Perceived social support measured using parent self‐report (Multiple Dimension Scale of Perceived Social Support, MSPSS) at baseline and 12 weeks post‐randomisation; 4. Health economic outcome measures using self‐report European Quality of Life 5 Dimensions (EQ‐5D‐5L), Recovering Quality of Life (Re‐QoL) and subsections 4.1, 4.2, 4.3 and 4.4, section 5 of Client Service Receipt Inventory (CSRI) at baseline and 12 weeks post‐randomisation; 5. Qualitative outcomes of the AADAPT intervention, collected in the format of semi‐structured interviews after 12 weeks post‐randomisation INCLUSION CRITERIA: Adolescent Parent: 1. Aged 16‐24 years 2. Child born within 12 months at the time of recruitment 3. Score 10 or above on EPDS 4. Lives in the UK 5. Able to provide free informed consent to participate 6. Sufficient understanding of English (secondary school level, age 11) reading ability as the self‐help package requires participants to read and understand the documents and suggested activities Peer Mentors (Parent Buddies): 1. Aged 25‐35 years 2. Had first baby when they were under 25 years old 3. Have had experience of low mood (defined as feeling low, down, depressed or stressed most days for 2 or more weeks) 4. Lives in the UK 5. Able to provide free informed consent to participate 6. Sufficient understanding of English (secondary school level, age 11) reading ability as they will be helping parents navigate the self‐help package

Isrctn (2023). "Evaluating the impact of sling provision and training upon maternal mental health." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The intervention comprised the provision of free sling hire and training in how to use the sling from Sheffield Sling Library. Participation involves completing a questionnaire within 6 weeks of the birth of their baby, and subsequently being randomly allocated to receive the sling plus training intervention either as soon as was convenient after randomisation, or after a wait period of 3 months. Participants then either received the intervention or were added to the waiting list to receive the intervention after 3 months. Participants completed questionnaires 6 and 12 weeks after the first questionnaire. Randomisation was undertaken using a computer‐generated random number sequence following a 1:1 randomisation ratio. Upon completion of baseline measures, intervention participants are invited to attend a two‐hour drop‐in session at the sling library. These drop‐in sessions are part of the sling library’s usual provision at the time of the study. In this usual provision, parents are welcome to stay for as long as they wish within this time period. In usual provision, parents typically attend these sessions seeking advice and to try using a sling for the first time before buying or hiring, as well as seeking advice for slings that they are already using (e.g. through a previous purchase or hire). All contact between staff and parents takes place within one large room. As such, staff may sometimes demonstrate a sling to a group of interested parents, and parents are able to meet and chat with each other, offering opportunities for the development of social networks and social support. To support the standardisation of session content and improve replicability, a checklist was created for use by sling library staff during CONDITION: Maternal mental health in the postnatal period ; Mental and Behavioural Disorders PRIMARY OUTCOME: Postnatal depression symptoms measured using the Edinburgh Postnatal Depression Scale at baseline, 6 weeks, and 12 weeks SECONDARY OUTCOME: ; Outcomes are assessed at baseline and 12 weeks:; 1. Maternal psychological well‐being scores measured using the Warwick‐Edinburgh Mental Wellbeing Scale (WEMWBS); 2. Parenting self‐efficacy and responsiveness measured using the Parenting Sense of Competency Scale (PSCS); 3. Caregiving behaviour measured using the Caregiving Experiences Questionnaire (CEQ); 4. Breastfeeding frequency and duration measured using bespoke questionnaire items; INCLUSION CRITERIA: 1. Expectant mothers due to give birth within the baseline data collection period 2. Able to travel to the sling library 3. Not regularly used a sling previously 4. Mothers of twins were included in the study but completed measures based on one child only

Isrctn (2023). "A feasibility trial of the digital Hope Programme for adults with polycystic ovary syndrome (Hope PCOS)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The Hope PCOS intervention will be hosted on a digital platform owned by Hope for The Community (H4C) Community Interest Company, a research social enterprise spinout company from Coventry University (https://www.h4c.org.uk). The Hope PCOS course is a structured programme of 2.5 hours a week across 6 weeks, consisting of videos, educational content, activities with homework suggestions and suggested additional resources. These are released at set times over the 6 weeks and can be studied asynchronously in smaller chunks at participants’ own pace. The intervention has been co‐created using the Antecedent‐Target‐Measure approach, combining input from adults living with PCOS, PCOS charity representatives and healthcare professionals supporting patients with PCOS. The intervention is based on self‐management theory and evidence from clinical and health psychology, including cognitive behavioural theory, hope, gratitude and self‐compassion. The content is structured into si Xsessions, including positive self‐management for PCOS, managing the stress of PCOS, feeding mind and body well, body image, intimacy and close relationships, staying healthy with PCOS and keeping PCOS in its place. The content comprises text, images, downloadable documents, and links to external websites, and is configured into interactive activities (e.g., quizzes, self‐monitoring tools, journals), supporting participants to learn and consolidate the content. The Hope PCOS programme also includes forums and messaging facilities that act as a conduit for communication between participants, peers and facilitators. Trained peer facilitators with lived experience with PCOS moderate the course and are trained to assist participants with goal‐setting and solution‐focused goal CONDITION: Self management and psychosocial wellbeing in adults with polycystic ovary syndrome (PCOS) ; Nutritional, Metabolic, Endocrine PRIMARY OUTCOME: ; Recruitment; Retention; Follow‐up; and Completion Rates, and adverse and serious adverse events; 1. Recruitment rates will be calculated from the following: (1) providing consent and (2) completing baseline questionnaires. Direct email from participants indicating refusal or declining to participate in the study indicating a refusal. These participants will still be offered access to the Hope PCOS intervention but will not be contacted further.; 2. Retention rates will be calculated as the percentage of participants attending all 6 programme sessions.; 3. Follow‐up rates will be calculated as the percentage of participants who complete all web‐based study questionnaires. Participants lost to follow‐up will be identified as those who do not complete the T1 or T2 questionnaires.; 4. Completion rates will be calculated as the percentage of participants who attended at least half of the intervention (3 sessions) and completed the study questionnaires.; 5. Participants will be requested to report any adverse events such as psychological distress to the study researchers.; ; Adherence and Engagement Measures; The intervention platform collects user engagement data, such as the number of pages viewed in each session and the number of goals set that assists the moderators with participant engagement and experience. We measure the mean percentage of pages viewed per session, and the number of posts or comments a participant made for key activities (e.g. setting goals, comments posted).; SECONDARY OUTCOME: ; The following outcomes will be measured at baseline, after the intervention (6 weeks after baseline), and at follow up (3 months after baseline):; 1. Health‐related quality of life questionnaire for polycystic ovary syndrome (PCOSQ‐50) assesses of quality of life of 50 items in si Xdomains; psychosocial and emotional; fertility; sexual function; obesity and menstrual disorders; hirsutism, and coping.; 2. The Warwick Edinburgh Mental Well‐being Scale (WEMWBS) assesses mental well‐being. The scale includes measures of positive affect, satisfying interpersonal relationships and positive u ctioning.; 3. The 9‐item Patient Health Questionnaire (PHQ‐9) assesses the frequency of experience of the symptoms of depression.; 4. The 7‐item Generalized Anxiety Disorder scale (GAD‐7) measures symptoms of generalized anxiety disorder.; 5. The 6‐item Self‐Efficacy for Managing Chronic Disease scale (SEMCD6) provides a robust measure of participants’ confidence to self‐manage their symptoms of LC. The questions relate to participants’ confidence that they can keep issues relating to their condition from interfering with daily life.; 6. System Usability Scale (SUS). The System Usability Scale (SUS) is reliable tool for measuring website an app usability.; ; Qualitative outcomes; A subset of participants will be randomly selected from the Intervention Group and Control Group to take part in post‐course interviews with the research team to explore issues relating to acceptability of the Hope PCOS course. We will aim to interview participants who completed all or most of the intervention (N=10), as well as those who completed fewer than half of the sessions (N=10), to gain a balanced evaluation to inform future co‐design of the intervention.; INCLUSION CRITERIA: 1. Age 18+ years 2. UK based 3. Self report that diagnosis of PCOS has been confirmed by participant's general practitioner and/or a hospital specialist. 4. Capacity to give informed consent 5. Ability to communicate in English, to participate in the intervention and complete outcome measures 6. Internet connection and internet‐enabled device.

István, B., et al. (2021). "Efficacy and safety of PARP inhibitor therapy in advanced ovarian cancer: a systematic review and meta-analysis."
	
Itkonen, F., et al. (2023). "Quality of life and sexual function after tension-free vaginal tape and polyacrylamide hydrogel injection for primary stress urinary incontinence: 3-year follow-up from a randomized clinical trial." International Urogynecology Journal 34(12): 2977-2984.
	Introduction and hypothesis: To assess quality of life (QoL) and sexual function outcomes at 3 years after tension-free vaginal tape (TVT) and polyacrylamide hydrogel injection (PAHG) for stress urinary incontinence (SUI). Method(s): In this randomized trial comparing TVT (n = 104) and PAHG (n = 108), we assessed changes in QoL and sexuality using the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire, Short Form (IIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and RAND-36 Item Health Survey (RAND-36) at baseline and at 3 years. This is a secondary analysis of a randomized, noninferiority trial comparing patient satisfaction after TVT and PAHG. Result(s): In both groups, incontinence-related QoL improved from the baseline (p < 0.00), except for difficulty emptying the bladder and pain/discomfort. Total scores of UDI-6 and IIIQ-7 were lower for TVT compared to PAHG (p < 0.00) indicating better QoL at 3 years. Urinary incontinence with sexual activity or fear of incontinence restricting sexual activity improved in both groups (p < 0.00), with higher scores for physical section subscale in PISQ-12 (p = 0.02) for TVT. Physical and social functioning (RAND-36) improved from the baseline in both groups (p < 0.01) with a better outcome in the TVT group for physical functioning (p = 0.00). Conclusion(s): Both TVT and PAHG improve QoL and sexual function in primary SUI with better incontinence and health-related QoL scores in the TVT group compared to the PAHG group at 3 years.Copyright © 2023, The Author(s).

Itkonen, F., et al. (2022). "Tension-Free Vaginal Tape and Polyacrylamide Hydrogel Injection for Primary Stress Urinary Incontinence: 3-Year Followup from a Randomized Clinical Trial." Journal of urology 208(3): 658-667.
	Purpose:We sought to determine whether polyacrylamide hydrogel (PAHG) is noninferior to tension-free vaginal tape (TVT) in the treatment of women with primary stress urinary incontinence (SUI).Materials and Methods:In this noninferiority trial, 223 women eligible for operative SUI treatment were randomized for TVT (110) or PAHG (113). Primary outcome was patient satisfaction and the noninferiority margin for the difference was 20%. Secondary outcomes were effectiveness and complications. Result(s):At 3 years, 188 (84.3%) women attended the followup. The satisfaction score (visual analogue scale 0-100) median was 98.5 (IQR 90-100) in the TVT group and 90.0 (IQR 70-100) in the PAHG group, whereas a score >=80 was reached in 87 (94.6%) and 65 (67.7%), respectively (difference 26.9%, 95% CI 16.7% to 36.8%). Thus, PAHG did not meet the noninferiority criteria set in our study. The cough stress test was negative in 88 (95.7%) of TVT patients vs 75 (78.1%) of PAHG patients (difference 17.5%, 95% CI 8.6% to 26.9%). Any peri- or postoperative complication before crossover between the groups was detected in 40 (43.5%) women in the TVT group and 23 (24.0%) women in the PAHG group (difference 19.5%, 95% CI 6.8% to 31.4%). Conclusion(s):In midterm followup, PAHG did not reach in patient satisfaction the noninferiority set in our study. Furthermore, mid urethral TVT slings show better subjective and objective cure rates than PAHG. However, complications were more often associated with TVT. Since the majority of PAHG treated women were also cured or improved, primary SUI women can be offered PAHG as a safe and durable alternative treatment.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Itkonen, F., et al. (2021). "Quality of life and sexual function after TVT surgery versus Bulkamid injection for primary stress urinary incontinence: 1 year results from a randomized clinical trial." International Urogynecology Journal 32(3): 595-601.
	INTRODUCTION AND HYPOTHESIS: To assess changes in quality of life (QoL) and sexual function outcomes at 1 year after tension-free vaginal tape (TVT) versus polyacrylamide hydrogel injection (PAHG). METHODS: In a randomized trial comparing TVT (n = 111) and PAHG (n = 113) treatments of stress urinary incontinence (SUI), we compared urinary incontinence and health-related QoL using the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire, Short Form (IIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and RAND-36 Item Health Survey (RAND-36) at baseline and 1 year. RESULTS: UDI-6 and IIQ-7 showed improved incontinence-related QoL (p = 0.001) from baseline in both groups except for difficulty emptying the bladder and pain/discomfort. At 1 year, TVT patients experienced less urinary symptom-related distress compared to PAHG (p < 0.001). Sexual function improved in both groups (p < 0.001 for TVT and p = 0.01 for PAHG) with higher scores for the physical section subscale (p < 0.001) for TVT. Health-related QoL (RAND-36) improved from baseline in both groups in physical and social functioning (p < 0.001) with better outcome in the TVT group for physical functioning (p < 0.001). Increase in pain from baseline (p = 0.02) was detected for TVT, but not for PAHG. However, there was no difference between the groups (p = 0.78). CONCLUSIONS: In primary SUI, TVT and PAHG treatments both improved QoL and sexual function at 1 year. However, incontinence and health-related QoL scores were better in the TVT group. More pain compared to the baseline was reported after TVT, although there was no difference between groups. Clinical significance needs to be evaluated in long-term follow-up.

Ito, H., et al. (2022). "Does the use of a uterine manipulator in robotic surgery for early-stage endometrial cancer affect oncological outcomes?" International Journal of Medical Robotics and Computer Assisted Surgery 18(6): e2443.
	Background: To investigate the impact of the use of a uterine manipulator in robot-assisted surgery for early-stage endometrial cancer on oncological outcome. Method(s): Eighty six robotic surgeries and sixty seven open surgeries were performed for early-stage endometrial cancer. Disease-free survival and overall survival at 5 years, and surgical results and postoperative complications were compared between surgeries. In robotic surgery, a uterine manipulator was used in all cases. Result(s): There was no significant difference in oncological outcome between surgeries. Robotic surgery showed significantly longer operative time, less blood loss, and shorter hospital stay compared to open surgery. In robotic surgery, complications occurred significantly less frequently, and no patients required conversion to laparotomy. There were no clear correlations of positive lavage cytology with The International Federation of Gynecology nd Obstetrics stage, recurrence, and site of recurrence in either surgery. Conclusion(s): The use of a uterine manipulator during robotic surgery for early-stage endometrial cancer did not influence recurrence or survival.Copyright © 2022 John Wiley & Sons Ltd.

Ito, H., et al. (2021). "Introduction of gasless laparoscopic surgery as a minimally invasive procedure for endometrial cancer and its usefulness from the viewpoint of the learning curve." World Journal of Surgical Oncology 19(1): 347.
	BACKGROUND: We investigated the usefulness of gasless laparoscopic surgery (GLS) using a subcutaneous abdominal wall lifting method for endometrial cancer. METHODS: We studied 105 patients with early endometrial cancer who underwent GLS (55) or open surgery (50). A uterine manipulator was used in all GLS cases. We compared operative time, blood loss, number of lymph nodes removed, hospital stay, perioperative complications, cases converted to laparotomy, and recurrence and survival rates. We also studied the learning curve and proficiency of GLS. RESULTS: The GLS group had significantly longer operative time (265 vs. 191 min), reduced blood loss (184 vs. 425 mL), shorter hospital stay (9.9 vs. 17.6 days), and fewer postoperative complications (1.8 vs. 12.0%) than the open group. No case was converted to laparotomy. Disease-free and overall survival rates at 4 years postoperatively (GLS vs. open groups) were 98.0 versus 97.8 and 100 versus 95.7%, respectively, and there was no significant difference between the groups. Regarding the learning curve for GLS, two different phases were observed in approximately 10 cases. Operator 2, who was not accustomed to laparoscopic surgery, showed a significant reduction in operative time in the later phase 2. CONCLUSIONS: GLS for endometrial cancer results in less bleeding, shorter hospital stay, and fewer complications than open surgery. Recurrence and survival rates were not significantly different from those of open surgery. This technique may be introduced in a short time for operators who are skilled at open surgery but not used to laparoscopic surgery.

Iwami, N., et al. (2023). "Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study." Journal of Assisted Reproduction and Genetics 40(1): 125-135.
	Purpose: A Lactobacillus-dominated microbiota in the endometrium was reported to be associated with favorable reproductive outcomes. We investigated in this study whether 16S ribosomal RNA (rRNA) gene sequencing analysis of the uterine microbiome improves pregnancy outcomes.; Methods: This prospective cohort study recruited a total of 195 women with recurrent implantation failure (RIF) between March 2019 and April 2021 in our fertility center. Analysis of the endometrial microbiota by 16S rRNA gene sequencing was suggested for all patients who had three or more failed embryo transfers (ETs). One hundred and thirty-one patients underwent microbial 16S rRNA gene sequencing (study group) before additional transfers, while 64 patients proceeded to ET without that analysis (control group). The primary outcome was to compare the cumulative clinical pregnancy rate of two additional ETs.; Main Results: An endometrial microbiota considered abnormal was detected in 30 patients (22.9%). All but one of these 30 patients received antibiotics according to the bacterial genus detected in their sample, followed by treatment with probiotics. As a result, the cumulative clinical pregnancy rate (study group: 64.5% vs. control group: 33.3%, p = 0.005) and the ongoing pregnancy rate (study group: 48.9% vs. control group: 32.8%, p = 0.028) were significantly increased in the study group compared to the control group.; Conclusion: Personalized treatment recommendations based on the microbial 16S rRNA gene sequencing of the uterine microbiota can improve IVF outcomes of patients with RIF.; Trial Registration: The University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000036050 (date of registration: March 1, 2019). (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Iwasa-Inoue, N., et al. (2022). "Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients." International Journal of Clinical Oncology 27(2): 441-447.
	Background: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting.; Methods: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III-IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m 2 ) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications.; Results: Twenty-four patients were included in this study. The median age was 55.5 years (37-80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7-92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred.; Conclusions: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved. (© 2021. Japan Society of Clinical Oncology.)

Izett-Kay, M., et al. (2022). "Hysterectomy or Hysteropexy? Long term follow-up from a randomised controlled trial." International Urogynecology Journal 33(2): 446.
	Introduction In the UK Vaginal hysterectomy (VH) with apical suspension is the preferred surgical procedure for the treatment of uterine prolapse [1]. Yet manywomen would prefer avoid hysterectomy, potentially explaining the increasing use of uterine sparing alternatives [2, 3]. Laparoscopic mesh sacrohysteropexy (LSH), one such alternative, appears to have a risk of both mesh associated complications and reoperation for recurrent apical prolapse in the medium term[4]. To date, there are limited data from randomised studies, and that which exists is limited in the length of follow-up. The aimof this study was to compare vaginal hysterectomy and laparoscopic mesh sacrohysteropexy for the treatment of uterine prolapse. Methods This was a randomised controlled trial of VH and LSH for the treatment of symptomatic uterine prolapse, for which the 1-year outcomes have previously been reported [5]. We utilised the prespecified primary outcome of reoperation for apical prolapse. Secondary outcomes included PGI-I in prolapse symptoms, the ICIQ-VS, ICIQ-FLUTS and PISQ-12 questionnaires, patient reported mesh complications and POPQ. Follow-up was undertaken at a minimum of seven years postoperatively. Chi-squared test was used tocompare dichotomous outcomes, Mann-Whitney U test was used to compare questionnaire scores and Kaplan-Meier survival analysis for the primary outcome was undertaken. Results 101 women were randomised and there was no significant differences in the baseline characteristics of each group. At an average of 100 months post operatively (range 84-119 months), 62 women attended for follow-up. The risk of reoperation for apical prolapse was 17.2% following VH and 6.1% following LSH (relative risk 0.34, 95% CI 0.07-1.68, p = 0.17), with Kaplan-Meier survivorship over time shown in Figure 1. The incidence of any reoperation for prolapse is shown in Table 1. Laparoscopic sacrohysteropexy was associated with a statistically significant higher apical suspension (POP-Q point C-5 vs.-4.25, p = 0.02) and longer total vaginal length (9cm vs. 6cm, p<0.001). There was no difference in the change in ICIQ-VS scores between the two groups (ICIQ-VS change-22 vs.-25, p = 0.59). The ICIQ-FLUTS scores at follow up were similar in both groups (9.5 and 9.4, p = 0.97), with no difference in either the filling, voiding or incontinence sub-scales. The percentage of patients reporting PGI-I in prolapse symptoms as 'very much better' and 'much better' was 86% after VH and 76% after LSH (p = 0.29). None reported mesh removal, mesh erosion or chronic pain attributed to the mesh. Conclusions There may be potential advantages to LSH that include a low risk of apical reoperation, optimal anatomical apical support, and increased total vaginal length, consistent previously reported data. Larger trials are needed for precise estimates to inform practice, however, our data will contribute to any future meta-analyses.

Izett-Kay Matthew, L., et al. (2022). "Laparoscopic sacrohysteropexy versus vaginal hysterectomy and apical suspension: 7-year follow-up of a randomized controlled trial." International Urogynecology Journal 33(7): 1957-1965.
	Introduction and Hypothesis: Laparoscopic mesh sacrohysteropexy offers a uterine-sparing alternative to vaginal hysterectomy with apical suspension, although randomised comparative data are lacking. This study was aimed at comparing the long-term efficacy of laparoscopic mesh sacrohysteropexy and vaginal hysterectomy with apical suspension for the treatment of uterine prolapse.; Methods: A randomised controlled trial comparing laparoscopic mesh sacrohysteropexy and vaginal hysterectomy with apical suspension for the treatment of uterine prolapse was performed, with a minimum follow-up of 7 years. The primary outcome was reoperation for apical prolapse. Secondary outcomes included patient-reported mesh complications, Pelvic Organ Prolapse Quantification, Patient Global Impression of Improvement in prolapse symptoms and the International Consultation on Incontinence Questionnaire Vaginal Symptoms, Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and PISQ-12 questionnaires.; Results: A total of 101 women were randomised and 62 women attended for follow-up at a mean of 100 months postoperatively (range 84-119 months). None reported a mesh-associated complication. The risk of reoperation for apical prolapse was 17.2% following vaginal hysterectomy (VH) and 6.1% following laparoscopic mesh sacrohysteropexy (LSH; relative risk 0.34, 95% CI 0.07-1.68, p = 0.17). Laparoscopic sacrohysteropexy was associated with a statistically significantly higher apical suspension (POP-Q point C -5 vs -4.25, p = 0.02) and longer total vaginal length (9 cm vs 6 cm, p < 0.001). There was no difference in the change in ICIQ-VS scores between the two groups (ICIQ-VS change -22 vs -25, p = 0.59).; Conclusion: Laparoscopic sacrohysteropexy and vaginal hysterectomy with apical suspension have comparable reoperation rates and subjective outcomes. Potential advantages of laparoscopic sacrohysteropexy include a lower risk of apical reoperation, greater apical support and increased total vaginal length. (© 2021. The Author(s).)

Izquierdo, A., et al. (2021). "Is Endometrial Scratching Beneficial for Patients Undergoing a Donor-Egg Cycle with or without Previous Implantation Failures? Results of a Post-Hoc Analysis of an RCT." Diagnostics (Basel, Switzerland) 11(7).
	Endometrial scratching (ES) has been proposed as a useful technique to improve outcomes in in vitro fertilization (IVF) cycles, particularly in patients with previous implantation failures. Our objective was to determine if patients undergoing egg-donor IVF cycles had better live birth rates after ES, according to their previous implantation failures. Secondary outcomes were pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and multiple pregnancy rate. We analysed the results of 352 patients included in the Endoscratch Trial (NCT03108157). A total of 209 were patients with one or no previous implantation failures (105 with an ES done in the previous cycle, group A1, and 104 without ES, group B1), and 143 were patients with at least two previous failed implantations (71 patients with ES, group A2, and 72 without ES, group B2). We found an improvement in pregnancy rates (62.9% in group A1 vs. 55.8% in group B1 vs. 70.4% in group A2 vs. 76.4% in group B2, p = 0.028) in patients with at least two previous implantation failures, but this difference was not statistically different when we compared clinical pregnancy rates (59.1% vs. 51.0% vs. 64.8% vs. 68.1% in groups A1, B1, A2 and B2, respectively, p = 0.104) and live birth rates (52.4% vs. 43.3% vs. 57.8% vs. 55.6% in groups A1, B1, A2 and B2, respectively, p = 0.218). According to these results, we conclude that there is no evidence to recommend ES in egg-donor IVF cycles, regardless of the number of previous failed cycles.

Izquierdo, A., et al. (2022). "Cumulative live birth rates in egg donor IVF cycles with or without endometrial scratching: Is there a residual effect in subsequent embryo transfers? Follow-up results of a RCT in clinical practice." Journal of Gynecology Obstetrics and Human Reproduction 51(4): 102335.
	Introduction: Endometrial scratching (ES) is a simple technique that has been claimed to improve pregnancy rates in patients undergoing assisted reproduction techniques. Our objective was to acknowledge the effects of ES in subsequent embryo transfers by assessing the cumulative live birth rates (LBR) in patients undergoing egg-donor in vitro fertilization (IVF).; Material and Methods: We performed a follow-up analysis of the cumulative reproductive outcomes of the 352 patients included in the Endoscratch Trial (NCT03108157) during the twelve months following the randomization date. We compared the outcomes of patients who underwent an ES for the second and/or successive embryo transfers versus those who did not have an ES performed, in order to determine a possible carry over effect that could lead to different LBR in these groups.; Results: Our analysis reveals that both groups (with and without ES performed before the first embryo transfer) had similar cumulative LBR (69.9% vs 65.9% in group A and B respectively, RR: 1.20, 95% confidence interval (CI): 0.92 - 1.22, p = 0.42). When we analyzed the results comparing patients who had received at least an ES before any of the embryo transfers during that period, we did not find any differences in LBR either (68.0% in patients with at least an ES and 67.8% in patients without ES, RR 1.00, 95%CI 0.87 - 1.16, p = 0.96).; Conclusion: According to our results, we cannot state that ES has a long term effect on endometrial receptivity of egg recipients as cumulative LBR do not differ from those of patients who do not receive it.; Competing Interests: Conflicts of Interest The authors declare no conflict of interest. (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Izquierdo, R., et al. (2020). "Endometrial Scratching Effect on Clinical Pregnancy Rates in Patients Undergoing Egg Donor In Vitro Fertilization Cycles: the ENDOSCRATCH Randomized Clinical Trial (NCT03108157)." Reproductive sciences (Thousand Oaks, Calif.) 27(10): 1863-1872.
	The potential benefit of endometrial scratching (ES) on embryo implantation is still a controversial subject. At present, the single retrospective study in egg donor IVF cycles concluded that ES has no beneficial effect. Our objective was to determine if there are differences in clinical pregnancy rates (CPR) in egg donor cycles when an ES is performed. This is a randomized controlled trial (RCT) in egg donor IVF patients conducted at ProcreaTec Fertility Center in Madrid. Three hundred fifty-two patients were included in total. One hundred sixty-one patients completed the protocol in group A and 172 patients in group B. Patients allocated to group A received an ES in the luteal phase of the cycle preceding the embryo transfer cycle. Group B patients did not receive any intervention. Primary outcome of this RCT was CPR. Secondary outcomes were implantation (IR), miscarriage (MR), ongoing pregnancy (OPR), multiple pregnancy (MulPR), and live birth rates (LBR). CPR was 104 of 161 (64.6%) in group A and 102 of 172 (59.3%) in group B (RR 1.09, 95% confidence interval (CI) (0.92-1.29); p = 0.378). OPR, MR, MulPR, and LBR were also comparable. No major complications were detected after ES and pregnancy complications were comparable. Our results show that there is no beneficial role of ES in egg donor IVF cycles, considering these patients as the ideal model as they share homogeneous embryo quality and endometrial preparation protocols. This trial was registered on April 5, 2017, as the ENDOSCRATCH trial (NCT03108157).

j, R. J. (2022). "Efficacy of local hemostatic material in ovarian endometriotic cyst surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: After obtaining consent prior to surgery, the test drug is applied intraperitoneally to the site of bleeding during surgery. CONDITION: D004715 surgery ; Endometrioma PRIMARY OUTCOME: 1) Number of times of electrocoagulation during surgery; 2) Cumulative time of electrocoagulation during surgery; The following items will be evaluated in the PureStat‐ and non‐use groups, as well as by site of bleeding in all patients. The number of ovarian bleeding sites, the number of ovarian bleeding sites that stopped spontaneously without hemostatic treatment, the number of ovarian bleeding sites that required hemostatic treatment, and the number of bleeding sites and hemostatic sites for each side of the ovary will be counted. For each ovarian bleeding site, the number of times of electrocoagulation, cumulative time of electrocoagulation, amount of PureStat used, hemostatic method, and the nature of bleeding (arterial or venous) are evaluated. SECONDARY OUTCOME: 1) Postoperative change in serum AMH level (percentage decrease from preoperative value); 2) Peritoneal bleeding at the site of detachment of peri‐ovarian adhesions associated with ovarian cyst removal: Count the number of bleeding sites, the number of sites where the bleeding stopped spontaneously without hemostatic treatment, and the number of peritoneal bleeding sites that required hemostatic treatment. For each site of peritoneal bleeding due to detachment of peri‐ovarian adhesions associated with ovarian cyst removal, the number of times of electrocoagulation, cumulative time of electrocoagulation, amount of PureStat used, hemostatic method, and nature of bleeding (arterial or venous) will be evaluated.; 3) Achievement rate of hemostasis with PureStat alone (number of bleeding sites hemostatic with PureStat alone/total number of bleeding sites); 4) Rebleeding rate after achieving hemostasis with PureStat alone (number of rebleeding sites/number of bleeding sites hemostatically stopped with PureStat alone); 5) Amount of PureStat used per case; 6) Douglas fossa echo free space INCLUSION CRITERIA: 1) Women between the ages of 20 and 40 2) Patients with unilateral or bilateral chocolate cysts diagnosed by MRI, ultrasound, or both. 3) Patients with at least one chocolate cyst with a diameter greater than 4 cm. 4) Patients with chocolate cysts not exceeding 10 cm in diameter on either bilateral ovaries 5) Patients for whom the decision to undergo laparoscopic ovarian cystectomy was made at a conference including at least 3 obstetricians/gynecologists. 6) Patients who are able to cooperate with condom contraception until the first postoperative month of outpatient visits or until the onset of the first postoperative menstrual period, whichever is longer. 7) Patients whose written consent to participate in this study has been obtained.

j, R. J. (2022). "Pyridoxamine for menopausal disorder." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: After informed consent is obtained, patients are registered provisionally, and are orally administered 2 placebo capsules a day, each after breakfast and supper, for 2 weeks. Those who did not respond to the placebo capsules are definitely registered and allotted to either the test group or the control group. Participants in the test group are administered 1,200 mg (4 capsules) of pyridoxamine per day, 2 capsules each after breakfast and supper. The participants in the control group are administered 4 capsules of placebo, 2 capsules each after breakfast and supper. Both groups are administered either pyridoxamine or placebo for 6 weeks. CONDITION: menopausal disorder with psychological symptoms PRIMARY OUTCOME: Improvement in depressive symptoms (decrease in the CES‐D score at week 6 compared to week 0) SECONDARY OUTCOME: Improvement in vasomotor symptoms (decrease in the Hot Flash Severity Inde Xfrom week 0 to week 6); Improvement in anxiety symptoms (decrease in the STAI score from week 0 to week 6) INCLUSION CRITERIA: [provisional registration] Those who fulfill all the items below will be registered provisionally: 1. those who have menopausal disorder with psychological symptoms by main doctor(excluding those who have symptoms due to cancer treatment) 2. those who responded as either moderate or severe to any of the MHR‐QOL items: #10 I feel less enthusiastic about things than before.; #11 Things I used to enjoy have become a bit of chore.; #12 I do less than I would like.; #16 I upset about small things.; #17 I feel nervous about small things. 3. those who are aged 40 to 64 years old 4. out‐clinic patients 5. female 6. those how are able to provide informed consent [definite registration] Those who fulfill the inclusion criteria item #2 after 2 weeks of placebo administration will be registered definitely.

Jabarpour, M., et al. (2024). "The modulating effects of astaxanthin on apoptosis in women with polycystic ovarian syndrome: A randomized clinical trial." Avicenna Journal of Phytomedicine 14(1): 64-77.
	Objective: Astaxanthin (ASX) is a lipid-soluble keto-carotenoid with several biological effects. These effects may benefit polycystic ovarian syndrome (PCOS) patients. Imbalanced apoptosis/anti-apoptosis signaling has been considered the major pathogenesis of PCOS. In a randomized clinical trial, we tested the impact of ASX on the apoptotic pathway in PCOS granulosa cells (GCs). The present study hypothesizes that ASX may improve apoptosis in PCOS patients. Material(s) and Method(s): This trial recruited patients with confirmed PCOS. A total of 58 patients were randomly assigned to take ASX (12 mg) or placebo for 8 weeks. Aspirated follicular fluid (FF) and blood samples were taken from both groups to measure BAX and BCL2 protein expression. Following FF aspiration, GCs from both groups were obtained; Real-Time PCR and Western blotting were used to evaluate the apoptotic pathway's gene and protein expression levels in GCs.BAXBCL2 Results: In GCs analysis, ASX reduced DR5 gene and protein expression after 8 weeks compared to placebo(p<0.05). Also, Caspase8 (p>0.05) and BAX (p<0.05) gene expression declined, although the difference was not statistically significant for Caspase8. Besides,ASX treatment contributed to an elevated BCL2 gene expression in GCs(p<0.05). In FF and serum analysis, a statistically significant increase was found in BCL2 concentration in the ASX group (p<0.05). Moreover, a reduction in BAX level was confirmed in both FF and serum of the ASX group; however, this change was not significant in the serum (p>0.05). Conclusion(s): It seems that ASX consumption among women with PCOS improved serum and FF levels of apoptotic factors and modulated genes and protein expression of the apoptosis pathway in GCs. Nevertheless, further investigations are needed to reveal the potential role of this compound in PCOS treatment.Copyright © 2024 Mashhad University of Medical Sciences. All rights reserved.

Jabarpour, M., et al. (2023). "Astaxanthin treatment ameliorates ER stress in polycystic ovary syndrome patients: a randomized clinical trial." Scientific Reports 13(1): 3376.
	Astaxanthin (ASX), as a natural carotenoid compound, exists in various types of seafood and microorganisms. It has several possible beneficial therapeutic effects for patients with polycystic ovary syndrome (PCOS). Patients with PCOS also suffer from endoplasmic reticulum (ER) stress. In the present work, it was hypothesized that ER stress could be improved by ASX in PCOS patients. Granulosa cells (GCs) were obtained from 58 PCOS patients. The patients were classified into ASX treatment (receiving 12 mg/day for 60 days) and placebo groups. The expression levels of ER stress pathway genes and proteins were explored using Western blotting and quantitative polymerase chain reaction. To assess oxidative stress markers, follicular fluid (FF) was gained from all patients. The Student's t test was used to perform statistical analysis. After the intervention, ASX led to a considerable reduction in the expression levels of 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and X-box-binding protein 1 compared to the placebo group, though the reduction in the messenger RNA (mRNA) expression level of activating transcription factor 6 was not statistically significant. However, ASX significantly increased the ATF4 expression level. GRP78 and CHOP protein levels represented a considerable decrease in the treatment group after the intervention. In addition, a statistically significant increase was found in the FF level of total antioxidant capacity in the treatment group. Based on clinical outcomes, no significant differences were found between the groups in terms of the oocyte number, fertilization rate, and fertility rate, but the ASX group had higher rates of high-quality oocytes, high-quality embryo, and oocyte maturity compared to the placebo group. Our findings demonstrated that ER stress in the GCs of PCOS patients could be modulated by ASX by changing the expression of genes and proteins included in the unfolding protein response.Trial registration This study was retrospectively registered on the Iranian Registry of Clinical Trials website ( www.irct.ir ; IRCT-ID: IRCT20201029049183N, 2020-11-27).Copyright © 2023. The Author(s).

Jabarpour, M., et al. (2024). "Astaxanthin supplementation impact on insulin resistance, lipid profile, blood pressure, and oxidative stress in polycystic ovary syndrome patients: A triple-blind randomized clinical trial." Phytotherapy research : PTR 38(1): 321-330.
	Astaxanthin (ASX) is a natural carotenoid compound found in several of microorganisms and seafood. It may have numerous therapeutic benefits for polycystic ovarian syndrome (PCOS) patients. The aim of this study was to investigate the effect of ASX on lipid profile, insulin resistance (IR), blood pressure (BP), and oxidative stress (OS) levels in infertile PCOS patients. Overall, 58 infertile women with diagnosed PCOS participated in this triple-blind randomized clinical trial. They were randomly assigned to two groups, taking either a placebo or ASX (2 × 6 mg/day) for 8 weeks. Blood serum samples were collected from patients before and after the intervention. Fasting Insulin (FI), fasting blood glucose (FBS), OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], and total antioxidant capacity [TAC]), and lipid profiles were evaluated in serum. Moreover, based on the relevant formula, several indices associated with IR were calculated. BP was also assessed at the start and end of the study. After 8 weeks of ASX consumption, a significant reduction was observed in fasting blood sugar, HOMA-IR, FI, MDA, low-density lipoprotein-cholesterol, and TC/HDL-C. Conversely, ASX significantly increased TAC, HDL-C, and QUICKI. After adjusting the analysis for the baseline values of age, body mass index, and biochemical parameters, non-significant values were obtained for QUICKI and FI, along with no changes in other findings. Overall, ASX appears to be an effective and safe supplement that alleviates insulin metabolism, lipid profile parameters, and OS in infertile PCOS patients. (© 2023 John Wiley & Sons Ltd.)

Jabarpour, M., et al. (2024). "Comparison of progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in terms of preventing premature LH surge and assisted reproductive technology outcome in infertile women: a randomized controlled trial." Archives of Gynecology and Obstetrics.
	INTRODUCTION: Progesterone can be used instead of GnRH agonists and antagonists in order to avert a premature LH surge during controlled ovarian stimulation (COS) protocol. Nonetheless, there is limited knowledge regarding its utilization. Thus, this study compared the effects of progesterone and GnRH antagonists (GnRH-ant) on premature LH surges and assisted reproductive technology (ART) results in infertile women undergoing ART. MATERIALS AND METHODS: In this clinical trial, the progesterone protocol (study group) and GnRH-ant protocol (control group) were tested in 300 infertile individuals undergoing IVF/ICSI. The main outcome was the number of oocytes retrieved. The secondary outcomes included premature LH rise/surge, the quantity of follicles measuring ≥ 10 and 14 mm, oocyte maturity and fertilization rate, the number of viable embryos, high-quality embryo rate and pregnancy outcomes. RESULTS: The study group exhibited a statistically significant increase in the number of retrieved oocytes, follicles measuring 14 mm or greater, and viable embryos compared to the control group (P < 0.05). The study group also increased oocyte maturity, chemical pregnancy rate, and clinical pregnancy rate (P < 0.05). Both groups had similar mean serum LH, progesterone, and E2 levels on trigger day. The control group had more premature LH rise than the study group, although this difference was not statistically significant. CONCLUSION: In conclusion, it can be stated that the progesterone protocol and the GnRH-ant protocol exhibit similar rates of sudden premature LH surge in infertile patients. However, it is important to note that the two regiments differ in their outcomes in ART. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT-ID: IRCT20201029049183N, 2020-11-27).

Jabbour, G. and D. Iancu Horia (2024). "Anaerobic and aerobic contributions to repeated supramaximal cycling exercises and their adaptation to high-intensity interval training in obese perimenopausal and postmenopausal women." Menopause (New York, N.Y.) 31(1): 39-45.
	Objective: This study investigated the anaerobic and aerobic contributions to total energy release during repeated supramaximal cycling exercises (SCE) and their adaptation in response to 6 weeks of high-intensity interval training (HIIT) in obese perimenopausal and postmenopausal women.; Methods: Nineteen perimenopausal women and 21 postmenopausal women with an average age of 50.1 years participated in the 6-week HIIT intervention. Before and after the training, the accumulated oxygen deficits (mL·min -1 ) and anaerobic and aerobic contributions (%) were measured in all groups via repeated SCE.; Results: The results showed that, before training, the anaerobic contributions to repeated SCE did not differ between the perimenopausal and postmenopausal women for the first three repetitions. However, a higher decrease was reported for postmenopausal women at the fourth and fifth repetitions ( P < 0.01, respectively). After HIIT, anaerobic contributions increased significantly in both groups ( P < 0.01, respectively). Nevertheless, postmenopausal women still had significantly lower anaerobic contributions to repeated SCE compared with perimenopausal women ( P < 0.01, respectively). Multiple linear regression analysis indicated that menopause status was an independent predictor of anaerobic contribution, accounting for 17%, 21%, 15%, 19%, and 22% of variations (β = 0.28, P = 0.03; β = 0.29, P = 0.04; β = 0.18, P = 0.05; β = 0.22, P = 0.05; and β = 0.33, P = 0.03 for the first to the fifth repetitions consecutively for perimenopausal vs postmenopausal groups).; Conclusions: A 6-week HIIT intervention increased the anaerobic contributions to energy in response to repeated SCE in obese perimenopausal and postmenopausal women. However, postmenopausal women had lower anaerobic contributions at the fourth and fifth repetitions mainly due to the effects of menopause.; Competing Interests: Financial disclosure/conflicts of interest: None reported. (Copyright © 2023 by The Menopause Society.)

Jackson, B., et al. (2022). "NUTRITIONAL EDUCATION (FACE-TO-FACE AND VIDEO INSTRUCTION) FOR POLYCYSTIC OVARY SYNDROME RESULTS IN GREATER REDUCTION IN BMI AND HEMOGLOBIN A1C THAN CALORIC RESTRICTION, EXERCISE AND METFORMIN." Fertility and Sterility 118(4 Supplement): e95.
	Objective: Polycystic ovary syndrome (PCOS) affects approximately 12% of women of reproductive age and increases risk of obesity, diabetes, heart disease, cancer and infertility. Metabolic inflexibility associated with PCOS makes weight loss difficult and has made nutritional education for this condition challenging and time-consuming. Hyperinsulinemia drives hyperandrogenism in PCOS. Research shows that carbohydrates from dairy and starch-based foods have greater insulinogenic properties than carbohydrates from non-starchy vegetables and fruits. The purpose of this study was to determine whether an 8-week dietary intervention with face-to-face or web-based nutritional instruction focusing on a low starch/low dairy diet would result in successful weight loss in women with PCOS. Material(s) and Method(s): Prospective randomized controlled trial including overweight/obese women with PCOS, age 18 to 45 years. Seventy-one participants enrolled, and 59 completed the study. Participants were randomized to 3 groups: Face-to-Face (F2F) Nutritional Instruction, 11-minute Web-based (Web) Nutritional Instruction or Standard Clinical Practice (SCP) (National Institutes of Health guidelines for recommended caloric intake and exercise frequency and metformin if elevated fasting glucose, fasting insulin or hemoglobin A1c). Baseline weight, BMI, waist and hip circumference, and hemoglobin A1c were recorded. Measurements and data analysis were performed by the institution's Clinical Research Insitute. Participants in treatment groups were permitted to eat lean meats, non-starchy vegetables, and low sugar fruits ad libitum until the point of satiety at every meal. Participants returned in 8 weeks for repeat weight, labs and anthropometric measurements. Result(s): Mean reduction of BMI was -2.9 (F2F), -2.3 (Web) and -0.05 (SCP)(p<.0001). There was a significant decrease in hemoglobin A1c in the treatment groups (-0.14) compared to SCP (0.03)(p=0.036) Treatment groups had reduction in waist of 3.09 inches compared to controls of 0.43 inch (p=0.002). Treatment groups had reduction in hips of 2.98 inches compared to controls of 0.77 inches (P<.0001). Conclusion(s): Nutritional education (either Face-to-Face or Web-based) of an 8-week low starch/low dairy diet resulted in greater reduction in BMI, hemoglobin A1c, waist circumference and hip circumference in PCOS patients versus standard clinical practice which consisted of caloric restriction, exercise and use of metformin. Effectiveness of an 11-minute web-based video instruction showed comparable results to in-person dietary instruction which shows promise in developing virtual tools to assist women with PCOS to achieve weight loss and improve glucose control. Impact Statement: Metabolic inflexibility and variation of symptoms has made management of PCOS challenging for both patients and their health care providers. A low starch/low dairy diet instuction (either in person or by 11-minute web-based video) shows more weight loss, lower hemoglobin A1c, and greater reduction in waist and hip circumference than standard clinical practice. Support: Laura W. Bush Institute for Women's HealthCopyright © 2022

Jackson, C. G., et al. (2022). "A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium." Gynecologic Oncology 166(1): 44-49.
	Objective: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer.; Patients & Methods: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival.; Results: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib.; Conclusions: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Jacomo, R. H., et al. (2020). "Exercise regimens other than pelvic floor muscle training cannot increase pelvic muscle strength-a systematic review." J. Bodywork Mov. Ther. 24(4): 568-574.
	BACKGROUND: Although pelvic floor muscle training is widely recommendedin the literature as the gold standard for the treatment of pelvic floor dysfunctions, such as urinary incontinence, interest in other exercise regimens is increasing. However, it is unknown whether other exercise regimens increase pelvic floor muscle strength. METHODS: This was a systematic review of randomized clinical trials found in PEDro, tridatabase, Cochrane and PubMed on the efficacy of nonspecific exercises, such as Pilates, the Paula method, and hypopressive exercises, in strengthening pelvic floor muscles in adults without underlying neurological disorders and with or without pelvic floor dysfunction. RESULTS: Seven studies were analyzed, and the results demonstrated that Pilates, the Paula method, and hypopressive exercises are ineffective in increasing pelvic muscle strength unless they are performed in conjunction with pelvic floor muscle training. The protocol was registered in the PROSPERO database (www.crd.york.ac.uk/prospero/) under the number CRD42019123396. CONCLUSION: Considering the available studies, we have concluded that Pilates, the Paula method and hypopressive exercises performed alone do not increase pelvic floor muscle strength. Pelvic floor muscle training continues to be the gold standard for increasing pelvic muscle strength.

Jaderek, I. and M. Lew-Starowicz (2019). "A Systematic Review on Mindfulness Meditation-Based Interventions for Sexual Dysfunctions." Journal of Sexual Medicine 16(10): 1581-1596.
	Introduction: Mindfulness-based therapies (MBT) are more and more frequently used in the treatment of sexual dysfunctions; therefore, it seems very important to assess evidence-based data on the clinical efficacy of these interventions. Aim(s): To provide a systematic review of published studies into the efficacy of MBT in the treatment of sexual dysfunctions. Method(s): The material for the analysis was obtained by searching 3 internet databases: EBSCO, PubMed, and ResearchGate. Articles describing therapeutic interventions on the basis of mindfulness and their efficiency in reducing sexual dysfunction symptoms in men and women were sought. Main Outcome Measure(s): 15 original research articles were included to the review: 4 articles were devoted to the analysis of the efficiency of the mindfulness-based therapy in the reduction of sexual dysfunction related to pain in the genital-pelvic area, 10 to desire or sexual arousal disorders or both in women, and 1 to erectile dysfunction in men. Result(s): Studies indicate that MBT led to improvement in subjectively evaluated arousal and desire, sexual satisfaction, and a reduction of fear linked with sexual activity, as well as improving the consistency between the subjectively perceived arousal and genital response in women. The research indicated that MBT did not make a significant change in a reduction of pain during sexual activities. Evidence-based data were found on the efficacy of MBT in the treatment of male erectile dysfunction in 1 study. Clinical Implications: MBT could be effectively used in the treatment of female sexual dysfunction, specifically to improve sexual arousal/desire and satisfaction and to reduce sexual dysfunction associated with anxiety and negative cognitive schemas. Strengths & Limitations: The few studies available are affected by several methodologic limitations, including small numbers of participants, patient selection, application of complex therapeutic interventions, and a lack of homework assessment, which makes definite conclusions difficult to draw. Conclusion(s): The effects of MBT in female sexual dysfunctions are promising. In future studies, the mindfulness-based monotherapies should be implemented to verify their potential in reducing symptoms of sexual dysfunction. More research is needed to explore the potential of MBT in the treatment of male sexual dysfunction. Jaderek I, Lew-Starowicz M. A Systematic Review on Mindfulness Meditation-Based Interventions for Sexual Dysfunctions. J Sex Med 2019;16:1581-1596.Copyright © 2019 International Society for Sexual Medicine

Jae, J., et al. (2022). "Efficacy of treatment for interstitial cystitis painful bladder syndrome : A systematic review and network meta-analysis."
	
Jafari, F., et al. (2021). "The effect of zinc supplementation on brain derived neurotrophic factor: A meta-analysis." Journal of Trace Elements in Medicine and Biology 66: 126753.
	Background: Zinc in one of the most abundant trace minerals in human body which is involved in numerous biological pathways and has variety of roles in the nervous system. It has been assumed that zinc exerts its role in nervous system through increasing brain derived neurotrophic factor (BDNF) concentrations. Objective(s): Present meta-analysis was aimed to review the effect of zinc supplementation on serum concentrations of BDNF. Methods and materials: Four electronic databases (Pubmed, Scopus, Web of Science, Embase) were searched for identifying studies that examined BDNF levels prior and after zinc supplementation up to May 2020. According to the Cochrane guideline, a meta-analysis was performed to pool the effect size estimate (Hedges' test) of serum BDNF across studies. Risk of publication bias was assessed using a funnel plot and Egger's test. Result(s): Five studies were eligible and 238 participants were included. These studies enrolled subjects with premenstrual syndrome, diabetic retinopathy, major depression disorder, overweight/obese and obese with mild to moderate depressive disorders. Zinc supplementation failed to increase blood BDNF concentrations with effect size of 0.30 (95 % CI: -0.08, 0.67, P = 0.119). Funnel plot did not suggest publication bias. Conclusion(s): Zinc supplementation may not significantly increase BDNF levels. However, the small number of included articles and significant heterogeneity between them can increase the risk of a false negative result; therefore, the results should be interpreted with caution.Copyright © 2021

Jafari-Koulaee, A., et al. (2020). "A Systematic Review of the Effects of Aromatherapy with Lavender Essential Oil on Depression." Central Asian journal of global health 9(1): e442.
	Introduction: Depression is considered as one of the most serious health issues worldwide, and the search for the most effective and safe treatments for depression is essential. Aromatherapy with lavender have attracted the attention of many researchers due to their low cost and ease of use, so this study was conducted to review of the effects of aromatherapy with lavender essential oil on depression.; Methods: This systematic review study was conducted by searching the databases (SID, Magiran, Google-Scholar, Medline via PubMed, Scopus, and Web of Science) by using the keywords such as depression, Lavandula, Lavender, and Aromatherapy, as well as applying OR and AND operators to the end of January 1, 2020 A.D. The inclusion criteria were: 1) Interventional studies that determined keywords were in the title or keywords of the article, 2) aromatherapy was conducted through inhalation or massage, 3) the full text of paper was accessible, and 4) published in English or Persian. Finally, the information obtained from articles was extracted using a checklist.; Results: Out of 278 studies, 9 studies were included to the systematic review process after screening and eliminating duplicate papers according to the purpose of the study. Aromatherapy with lavender essential oil was conducted on the patients suffering from migraine, patients with the acute coronary syndrome, patients undergoing hemodialysis, community-dwelling older adult, and postpartum depression. The results obtained from some studies showed the positive effect of aromatherapy with lavender essential oil on depression whereas some studies did not report the effect of aromatherapy with lavender on depression significantly.; Conclusions: It seems that aromatherapy with lavender probably can be used as a complementary, simple, and inexpensive method to improve mild and moderate depression. It is recommended to earmark using a collaborative approach and make use of interdisciplinary and psychology specialists as well as complementary medicine in applying aromatherapy with lavender essential oil. (Copyright © 2020 Azar Jafari-Koulaee, Forouzan Elyasi, Zohreh Taraghi, Ehteram Sadat Ilali, Mahmood Moosazadeh.)

Jafarpour, S., et al. (2020). "Association of serum and follicular fluid leptin and In Vitro Fertilization/ ICSI outcome: A systematic review and meta-analysis." Journal of Gynecology Obstetrics and Human Reproduction 50(6): 101924.
	There are conflicting reports regarding circulating leptin and its relationship between pregnancy outcomes in infertile women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We performed a systematic review and meta-analysis to assess the association between serum or follicular fluid (FF) leptin concentrations reported for infertile women and their IVF outcome. A systematic search was undertaken in available databases (PubMed, Scopus, Web of Science, The Cochrane Library and Embase) to find studies published up to Aug 2020 and the standardized mean difference with 95% confidence interval was taken from 14 eligible studies. Both graphical (funnel plots) and test methods (Egger's regression test and the Begg) assessed the presence of publication bias. Subgroup analysis was used to investigate the source of heterogeneity. Pooled effect sizes indicated no asignificant difference between non-pregnant women and those post-IVF with respect to leptin concentration in follicular fluid and on the day of ovum pick-up (OPU) and day of HCG (human chorionic gonadotrophin) administration. Based on present eligible papers included in this meta-analysis there is no statistically significant correlation between leptin levels in pregnant and non-pregnant women who underwent IVF/ICSI cycles. However, combination of leptin in serum and/or FF with other parameters may be a useful marker to predict IVF outcome.

Jafarzadeh, E., et al. (2022). "Combined regimens of cisplatin and metformin in cancer therapy: A systematic review and meta-analysis." Life Sciences 304: 120680.
	Introduction: Cancer cell resistance to chemotherapy agents is a challenging issue in treating patients with cancer. Findings suggest that a combination of drugs may have synergistic or additive effects. in the present study, we systematically reviewed the combined regimens of metformin with cisplatin in various treating cancers. Method(s): A comprehensive systematic search was performed in PubMed, Scopus, Embase, and other relevant databases with the following keyword "metformin", "cisplatin", "combination", "using all their equivalents and similar terms. Pooled odds ratio (OR) and 95% confidence intervals of cell viability and tumor volume as primary outcomes were calculated using Der-Simonian and Laird method while random effects meta-analysis was used, taking into account clinical and statistical heterogeneity. Result(s): Overall, 44 studies were retrieved, Findings of the present meta-analysis showed that combined regimens of metformin plus cisplatin was significantly associated with decreased odds of tumor volume and cell viability for all cancers compared with cisplatin alone (pooled OR: 0.40; 95% CI: 0.27, 0.58) and (pooled OR: 0.49; 95% CI: 0.42, 0.58) respectively. The result was same for cell viability in lung cancer (pooled OR: 0.59; 95% CI: 0.49, 0.70). The tumor size reduction and the response rate were evident in the animal xenografts model. Conclusion(s): Findings indicated that combining metformin with cisplatin is a practical therapeutic approach to increase treatment efficacy in the case of cell viability and tumor volume and minimize side effects. A combination of metformin with cisplatin could enhance treatment efficacy through synergistic inhibitory effects on the growth of cancer cells.Copyright © 2022

Jaffar, A., et al. (2022). "Persuasive Technology in an mHealth App Designed for Pelvic Floor Muscle Training Among Women: Systematic Review." JMIR mHealth and uHealth 10(3): e28751.
	BACKGROUND: Pelvic floor muscle training (PFMT) is one of the first-line treatments for stress urinary incontinence among pregnant women. Mobile health (mHealth) technology is potentially effective for delivering PFMT to pregnant women. Persuasive technology in the development of such mobile apps may facilitate behavior change by improving adherence to the exercises. The Capability, Opportunity, and Motivation-Behavior (COM-B) model is potentially useful in selecting the appropriate interventions to be incorporated into the apps. OBJECTIVE(S): This review of mHealth apps for PFMT aims to describe the principles of persuasion used for each app and to propose mHealth app design features based on the COM-B model. METHOD(S): A systematic literature search was conducted to answer three main research questions: what are the available mHealth apps for PFMT in the published literature, what persuasive strategies were used in their studies how were they mapped to the COM-B model, and how effective were the selected persuasive strategies for PFMT adherence? We searched PubMed, CINAHL, Web of Science, Scopus, and local Malaysian databases such as MyCite and MyMedR for articles reporting mHealth apps used for the delivery of PFMT. We included original articles reporting experimental and cross-sectional studies, including pilot or feasibility trials. Systematic and narrative reviews were excluded. Narrative and thematic syntheses were conducted on the eligible articles based on the research questions. The Cochrane risk of bias tool and the Risk of Bias Assessment Tool for Non-randomized Studies were used to assess study bias. RESULT(S): Of the 169 records from the initial search, 10 (5.9%) articles meeting the selection criteria were included in this review. There were 8 mHealth apps designed for the delivery of PFMT. The Tat, which used 3 categories of persuasive system design, improved PFMT adherence and was cost-effective. Only 1 app, the iBall app, used all categories of persuasive system design, by including social support such as "competition" in its design. The Diario Saude app was the only app developed using operant conditioning. All apps incorporated Tailoring and Expertise as part of their PSD strategies. Only 3 apps, the Diario Saude, Tat, and Pen Yi Kang demonstrated improved PFMT adherence. CONCLUSION(S): Persuasive technology used in mobile apps may target desired behavior change more effectively. The persuasive system design can be mapped to the COM-B model to explain its effectiveness on behaviour change outcomes.Copyright ©Aida Jaffar, Chai-Eng Tan, Sherina Mohd-Sidik, Novia Admodisastro, Felicity Goodyear-Smith. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 22.03.2022.

Jahanshahi, M., et al. (2022). "The effect of intrauterine hCG injection before embryo transfer on pregnancy rate in frozen embryo transfer cycles." Annals of Medicine and Surgery 79.
	Objective: HCG (human chorionic gonadotropin), which is secreted by cytotrophoblast cells, plays an important role in improving pregnancy outcomes among patients with infertility or related problems. In this study, we evaluate the effect of intrauterine hCG injection prior to frozen embryo transfer on pregnancy outcomes. Methods: In this clinical trial study, among women with infertility problems referred to (XXX) and those with frozen embryos were included in the study. 155 patients in the intervention group received 500 units of hCG while 157 in control group received saline prior to embryo transfer. Along with demographic data, successful in vitro fertilization and clinical pregnancy, loss of pregnancy, successful transplantation, and biochemical parameters were compared among the two groups. Results: The mean age of the patients included in the study was 32.97 ± 3.31 years. The level of anti‐Mullerian hormone, follicle stimulating hormone and the grade of frozen embryos were not significantly different between the two groups (P > 0.05). The rate of laboratory pregnancy in the intervention group was significantly higher than in the control group (51% vs 35%), p = 0.006. The rate of successful implantation and clinical pregnancy in the intervention group was also significantly higher, p = 0.01 and p = 0.006, respectively. Overall loss of pregnancy in intervention group was 78.1% and 86.0% in control group which was not significantly different, p = 0.068. Conclusion: The outcomes of our study showed that 500 IU of hCG prior to embryo transfer improves the rate of clinical and laboratory pregnancy. However, it does not reduce the rate of loss of pregnancy. Further studies are therefore required in this area.

Jahanshahi, M., et al. (2023). "The effect of misoprostol with and without letrozole in inducing successful medical abortion." Iranian Journal of Obstetrics, Gynecology and Infertility 25(11): 8-15.
	Introduction: The pharmacological approach of abortion is a safe and effective alternative to surgical procedures that is associated with a high level of patient's satisfaction. The present study was performed with aim to evaluate the effect of misoprostol with and without letrozole in the treatment of successful medical abortion and its relationship with BHCG titration level and cervical length. Method(s): This two-group randomized clinical trial study was performed in 2021 on 168 pregnant women under 18 weeks of gestation who were candidates for termination of pregnancy. The patients were randomly divided into two groups: A (misoprostol and letrozole) and B (misoprostol and placebo). Initial tests, betaHCG titration, ultrasound and cervical length were performed for all patients on the first day of hospitalization. After receiving the drug, all patients underwent ultrasound on the fifth day to evaluate complete abortion and removal of pregnancy residues. Data were analyzed by SPSS software (version 22) and Chi-square, independent t and logistic regression tests. P<0.05 was considered statistically significant. Result(s): The results showed that misoprostol + letrozole had a more successful abortion rate than misoprostol + placebo (88.1% vs. 59.5%). Increased cervical length was associated with a higher probability of miscarriage (P <0.001), while BHCG titration did not show a predictive role in induction of abortion (p>0.05). Conclusion(s): Adding letrozole to misoprostol for inducing abortion leads to an increase in the percentage of successful abortion and a reduction in the use of curettage.Copyright © 2023, Mashhad University of Medical Sciences. All rights reserved.

Jain, L., et al. (2021). "Effectiveness of Individualised Homoeopathic Medicines versus Conventional Treatment in the Management of Primary Dysmenorrhoea in Young Unmarried Females: a Randomised, Open-Label, Clinical Study." Homoeopathic links 34(2): 93‐99.
	
Jain, N., et al. (2021). "Cabergoline effectively reduces pain and preserves ovarian function in women with endometriosis." BJOG 128(SUPPL 2): 43‐44.
	Objective To compare the efficacy of dopamine receptor agonists with Gonadotropin releasing hormone agonists in reducing the pain and size of endometrioma. Design A prospective, open labelled, randomized controlled trial. Setting Department of Obstetrics and Gynaecology, AIIMS, New Delhi from January 2016 to June 2017. Materials and methods Fifty women with endometrioma and fulfilling the eligibility criteria were chosen and were randomized in two groups. Group I (n = 25) received 3.75 mg leuprolide acetate monthly for 4 months and Group II (n = 25) received 0.5 mg Tab Cabergoline 0.5 mg twice weekly for 4 months. VAS score was assessed before treatment, at 2 months, 4 months of treatment and 3 months after stopping the drug. The size of endometrioma and serum level of TNF‐α, CA‐125, prolactin and highly sensitive C‐reactive protein (hs‐CRP) were measured before and after treatment. Results The mean age of women in group I was 28.4 ± 3.9 years and 27.3 ± 5.4 years. The baseline VAS score in group I and group II were 7.2 ± 1.3 and 6.9 ± 1.1 respectively, while the mean reduction in VAS score after 4 months of treatment were 3.9 ± 1.3 (54.2%) and 3.2 ± 1.2 (46.4%) respectively. The median volume of endometrioma in group I was 28.73 cm3 (18.45‐45.37) and in group II was 27.21 cm3 (14.45‐47.64) which reduced to 11.35 cm3 (9.26‐20.56) and 16.86 cm3 (8.94‐24.39) respectively. Serum TNF‐α levels was done in 15 women. The baseline median value of serum TNF‐α in Group I was 1.75 (0.38‐3.46) pg/ml and in Group II was 0.75 (0.39‐ 2.87) pg/ml which reduced to 0.61 (0.20‐1.45) and 0.35 pg/ml (0.11‐0.67) respectively. The fall in serum TNFα levels was significantly more in Group II (P = 0.038) than Group I (P = 0.173). There was no significant difference seen in serum CA‐125, prolactin and hs‐CRP level in both the groups (P > 0.05). Amenorrhea was achieved in 80% women after 3 doses of leuprolide while in cabergoline group women had normal menstrual cycle. Conclusion Cabergoline was found to be as effective as GnRH agonists in reducing pain and size in endometriosis due to its anti‐angiogenic properties against vascular endothelial growth factor (VEGF) with minimal side effects.

Jakub, W., et al. (2023). "Impact of oral contraceptives on the gut microbiota composition in women with polycystic ovary syndrome: a systematic review."
	
Jallah John, K., et al. (2023). "Public Health Approach in the Elimination and Control of Cervical Cancer: A Review." Cureus 15(9): e44543.
	Public health experts worldwide have emphasized cervical cancer since it is a substantial global health burden primarily affecting women. This article thoroughly reviews the public health approach to eradicating and managing cervical cancer. The public health community seeks to lower the prevalence, morbidity, and mortality linked to this preventable disease by integrating primary prevention by means of vaccination against the human papillomavirus (HPV), secondary prevention using screening and early identification, and tertiary prevention through improved therapy and supportive care. In order to accomplish broad vaccination coverage and ultimately effectively prevent cervical cancer, it remains crucial to address obstacles to vaccine accessibility, reluctance, and fair distribution. Early identification and subsequent treatments depend greatly on cervical cancer screening programs. This study explores several screening methods, such as Papanicolaou (Pap) tests based on cytology and cutting-edge technologies like molecular assays and HPV detection. The detection of precancerous lesions and early-stage malignancies, permitting prompt treatment, has shown significant promise when integrating these technologies into coordinated population-based screening programs. The study also underlines the significance of addressing cervical cancer burden inequities, particularly in resource-constrained areas where access to preventative and curative care is constrained. Innovative and affordable methods for addressing marginalized groups are studied, including community-based outreach programs, mobile health technology, and local healthcare practitioners and community leaders in awareness campaigns. The research also examines improvements in cervical cancer treatment procedures, such as surgery, radiation, chemotherapy, and immunotherapy. It improves therapeutic efficacy and patient survival rates by incorporating various modalities into a multidisciplinary strategy. Highlighted palliative care and psychological support are crucial for patients who have advanced cervical carcinoma.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Jallah et al.)

Jamal Dinah, F., et al. (2022). "Human Papillomavirus 16 E2 as an Apoptosis-Inducing Protein for Cancer Treatment: A Systematic Review." International Journal of Molecular Sciences 23(20).
	Human papillomavirus type 16 (HPV-16) is a well-known etiological factor for cervical and oropharyngeal cancers. The E2 protein, the product of an early-transcribed gene in HPV-16, is postulated to cause the death of cancerous cells via p53-dependent and p53-independent pathways. The main aim of the present systematic review was to study the HPV 16-E2 protein as an apoptosis-inducer agent. A thorough search of MEDLINE/PubMed, Science Direct, Scopus, and EBSCOhost databases was conducted for relevant studies on HPV AND apoptosis OR cell death where HPV 16-E2 was involved. The search identified 967 publications. Eleven records dated from 1 January 1997 to 16 February 2022 were found to meet the inclusion criteria and were eligible for data extraction and inclusion. All studies concluded that HPV 16-E2 was able to induce cell death in transfected cells. E2 proteins from the high-risk HPV-16 were able to induce apoptosis through different apoptotic pathways depending on the location of the expressed gene. However, the mechanism was still unclear, and further studies are warranted.; Competing Interests: The authors declare no conflict of interest.

Jamebozorg, N., et al. (2023). "The Effect of Metabolic Persian Diet on Ovulation Induction in Infertile Women." Evidence-based complementary and alternative medicine : eCAM 2023: 6656779.
	Introduction: Infertility is an important issue with a high social and psychological burden. From the perspective of Persian Medicine (PM), uterine cold temperament is one of the important causes of female infertility.; Aim: The aim of this study was to study the effect of PM or Iranian traditional medicine on improving ovulation and fertility.; Methods: From January 2017 to August 2017, sixty infertile women with eugonadotropic ovulation disorder were randomly divided into two groups. Both groups were treated with clomiphene citrate, except that the intervention group also received metabolic Persian diet (MPD). In each cycle, the dominant follicles and endometrium were investigated with ultrasound. At the end of the cycle, beta human chorionic gonadotropin ( β- HCG) was evaluated and if positive, another ultrasound was performed two weeks later to confirm early pregnancy.; Results: The number of dominant follicles from the first to third cycle increased from 2.15 ± 1.14 to 2.28 ± 0.61 in the intervention group and decreased from 1.86 ± 0.79 to 1.30 ± 0.47 in the control group. The dominant follicle size changed from 16.00 ± 4.08 to 18.78 ± 2.78 and from 15.05 ± 3.11 to 15.80 ± 3.89 in the intervention and control groups, respectively. But endometrial thickness did not change significantly in the intervention group. Pregnancy results based on β- HCG and ultrasound findings were positive in 19 and 16 patients in the intervention group and in 10 and 7 patients in the control group, implying significantly higher numbers in the first group.; Conclusion: It seems that MPD may be effective in the success of ovulation induction.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2023 Nasrin Jamebozorg et al.)

James Racheal, L., et al. (2024). "Development of an FRα Companion Diagnostic Immunohistochemical Assay for Mirvetuximab Soravtansine." Archives of pathology & laboratory medicine.
	Context.—: Folate receptor-α (FRα, encoded by the FOLR1 gene) is overexpressed in several solid tumor types, including epithelial ovarian cancer (EOC), making it an attractive biomarker and target for FRα-based therapy in ovarian cancer.; Objective.—: To describe the development, analytic verification, and clinical performance of the VENTANA FOLR1 Assay (Ventana Medical Systems Inc) in EOC.; Design.—: We used industry standard studies to establish the analytic verification of the VENTANA FOLR1 Assay. Furthermore, the VENTANA FOLR1 Assay was used in the ImmunoGen Inc-sponsored SORAYA study to select patients for treatment with mirvetuximab soravtansine (MIRV) in platinum-resistant EOC.; Results.—: The VENTANA FOLR1 Assay is highly reproducible, demonstrated by a greater than 98% overall percent agreement (OPA) for repeatability and intermediate precision studies, greater than 93% OPA for interreader and greater than 96% for intrareader studies, and greater than 90% OPA across all observations in the interlaboratory reproducibility study. The performance of the VENTANA FOLR1 Assay in the SORAYA study was evaluated by the overall staining acceptability rate, which was calculated using the number of patient specimens that were tested with the VENTANA FOLR1 Assay that had an evaluable result. In the SORAYA trial, data in patients who received MIRV demonstrated clinically meaningful efficacy, and the overall staining acceptability rate of the assay was 98.4%, demonstrating that the VENTANA FOLR1 Assay is safe and effective for selecting patients who may benefit from MIRV. Together, these data showed that the assay is highly reliable, consistently producing evaluable results in the clinical setting.; Conclusions.—: The VENTANA FOLR1 Assay is a robust and reproducible assay for detecting FRα expression and identifying a patient population that derived clinically meaningful benefit from MIRV in the SORAYA study. (© 2024 College of American Pathologists.)

James-Hawkins, L., et al. (2019). "Human and economic resources for empowerment and pregnancy-related mental health in the Arab Middle East: a systematic review." Archives of Women's Mental Health 22(1): 1-14.
	This systematic review synthesizes research on the influence of human and economic resources for women's empowerment on their pre- and postnatal mental health, understudied in the Arab world. We include articles using quantitative methods from PubMed and Web of Science. Two researchers reviewed databases and selected articles, double reviewing 5% of articles designated for inclusion. Twenty-four articles met inclusion criteria. All 24 articles measured depression as an outcome, and three included additional mental health outcomes. Nine of 17 studies found an inverse association between education and depression; two of 12 studies found contradictory associations between employment and depression, and four of six studies found a positive association between financial stress and depression. These results suggest that there is a negative association between education and depression and a positive association between financial stress and depression among women in the Arab world. Firm conclusions warrant caution due to limited studies meeting inclusion criteria and large heterogeneity in mental health scales used, assessment measures, and definitions of human and economic resources for women's empowerment. It is likely that education reduces depression among postpartum women and that financial stress increases their depression. These findings can be used to aid in the design of interventions to improve mother and child outcomes. However, more research in the Arab world is needed on the relationship between human and economic resources for women's empowerment and perinatal mental health, and more consistency is needed in how resources and mental health are measured.

Jamilian, M., et al. (2022). "Correction: a Trial on the Effects of Magnesium-Zinc-Calcium Vitamin D Co-supplementation on Glycemic Control and Markers of Cardio-metabolic Risk in Women with Polycystic Ovary Syndrome." Archives of Iranian medicine 25(8): 577.
	This corrects the article: “A trial on the effects of magnesium‐zinc‐calcium vitamin D co‐supplementation on glycemic control and markers of cardio‐metabolic risk in women with polycystic ovary syndrome”1 published on “2017;20(10):640‐645” in the Archives of Iranian Medicine journal. In the original version of this article, participants was wrongly reported 60 in the results, while the correct participants is 30 in each group. In addition, in the conclusions section, a citation from our previous paper was omitted. The correct conclusions are another article by Maktabi et al39 with the same clinical trial described identical study timelines, location, sample size, randomization methods showed that co‐supplementation had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress. 39. Maktabi M, Jamilian M, Asemi Z. Magnesium‐Zinc‐Calcium‐Vitamin D Co‐supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: A Randomized, Double‐Blind, Placebo‐Controlled Trial. Biol Trace Elem Res. 2018 Mar; 182(1):21‐28.

Jamshidi, M. S., et al. (2022). "Biofeedback, biofeedback plus fiber laxative, and biofeedback plus osmotic laxative regimens to treat constipation in patients with pelvic floor dyssynergia: A randomized controlled trial." Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology 41(2): 160-168.
	BACKGROUND: Pelvic floor dyssynergia (PFD) is one of the causes of chronic constipation. Laxative-based therapies are not very effective in treating this type of constipation. The therapeutic effectiveness of three therapeutic strategies, including biofeedback (BOF) alone, BOF+ fiber laxative (psyllium), and BOF +osmotic laxative (polyethylene glycol; [PEG]), was assessed in patients with constipation secondary to PFD. METHODS: Eighty-eight patients with constipation were included during a period from 2017 to 2018. Thirty-two patients were treated with BOF alone, 25 patients received BOF+ fiber laxative (psyllium), and 31 patients received BOF+ osmotic laxative (PEG) for 2 to 3 months. A checklist was used to compare outcomes before and after the interventions. RESULTS: Satisfaction rates from the treatments were 60.83%, 46.88%, and 41.32% in the BOF, BOF + psyllium, and BOF + PEG groups, respectively. Women had a higher satisfaction rate compared to men. Defecation quality improved, and the frequency of enema usage decreased (p <0.05) in all the groups after intervention. Difficulty in evacuation, need for digitation, and return to the toilet after defecation significantly improved in the BOF alone group. Using laxatives reduced straining during evacuation and increased the duration of defecation. All the three regimens reduced rectal bleeding (p <0.05). CONCLUSIONS: Combinations of laxatives with BOF did not offer significant therapeutic benefit. As laxatives may cause dissatisfaction and incomplete/prolonged defecations in patients with PFD, adding laxatives to the BOF regimen is not recommended for these patients.

Janaina Das GraÇAs Da Silva, R., et al. (2023). "The Effect of Blue LED in the Treatment of Vaginal Candidiasis: A Systematic Review."
	
Janda, M., et al. (2021). "Complete pathological response following levonorgestrel intrauterine device in clinically stage I endometrial adenocarcinoma: Results of a randomized clinical trial." Gynecologic Oncology 162(Supplement 1): S43.
	Objectives: Intrauterine levonorgestrel (LNG-IUD) is used to treat patients with endometrial adenocarcinoma (EAC) and endometrial hyperplasia with atypia (EHA) but limited evidence is available on its effectiveness. The study determined the extent to which LNG-IUD with or without metformin (M) or weight loss (WL) achieves a pathological complete response (pCR) in patients with EAC or EHA. Method(s): This phase II randomized controlled clinical trial enrolled patients with histologically confirmed, clinically stage 1 FIGO grade 1 EAC or EHA; a body mass index (BMI) >30 kg/m2; a depth of myometrial invasion of less than 50% on MRI; a serum CA125 <= 30 U/mL. All patients received LNG-IUD and were randomized to observation (OBS), M (500 mg orally twice daily), or WL (pooled analysis). The primary outcome measure was the proportion of patients developing a pCR (defined as absence of any evidence of EAC or EHA) after 6 months. Result(s): From December 2012 to October 2019, 165 patients were enrolled and 154 completed the 6-months follow up. Women were on average 53 years of age, with BMI 48kg/m2. A total of 96 patients were diagnosed with EAC (58%) and 69 patients with EHA (42%). A total of 35 participants were randomized to OBS, 36 to WL and 47 to M (10 patients were withdrawn). After 6 months, the rate of pCR was 61% (95% CI 42% to 77%) for OBS, 67% (95% CI 48% to 82%) for WL and 57% (95% CI 41% to 72%) for M. Across the 3 treatment groups, the pCR was 82% and 43% for EHA and EAC, respectively. Conclusion(s): Complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups.Copyright © 2021 Elsevier Inc.

Jander, J., et al. (2021). "The efficiency of the use of agnus-castus on the clinical treatment of Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD): a systematic review."
	
Janeczko, M., et al. (2022). "Inhibitory effect of a combination of baicalein and quercetin flavonoids against Candida albicans strains isolated from the female reproductive system." Fungal biology 126(6-7): 407-420.
	Flavonoids are a diverse group of compounds originating from several natural plant sources. Various biological effects of flavonoids have been reported, including antimicrobial and antifungal activities. In this study, we showed the possibility of using commercial flavonoids, i.e. baicalein and quercetin, based on natural equivalents as compounds with antifungal properties against Candida albicans species. The effects of baicalein and/or quercetin were investigated using reference C. albicans strain and 50 clinical strains isolated from vulvovaginal candidiasis (VVC) patients. Baicalein and quercetin MIC values against C. albicans strains ranged between 0.5 and 256 μg/ml. We observed predominantly indifferent, synergistic, or partially synergistic interactions between both flavonoids and between the flavonoids and fluconazole in the treatment of planktonic cells of the C. albicans strains. Treatment with the flavonoid complex inhibited adhesion and aggregation of cells, cell surface hydrophobicity (CSH), flocculation, biofilm formation and reduced hyphal growth. Real-time RT-PCR revealed that baicalein and quercetin in combination down-regulated the expression of biofilm-specific genes. Finally, we observed increase in the cell membrane permeability of C. albicans and its physical destruction as a result of the synergistic activity of baicalein and quercetin. Our research evidences the effectiveness of baicalein and quercetin applied in combination as potential anti-Candida agents.; Competing Interests: Declaration of competing interest The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Jang, S., et al. (2020). "Acupuncture for in vitro fertilization in women with poor ovarian response: a systematic review." Integrative Medicine Research 9(2): 100395.
	Background: Poor ovarian response (POR) is one reason for infertility. In vitro fertilization (IVF) is frequently used to help achieve pregnancy, and performing acupuncture before IVF may promote ovulation and reduce egg retrieval pain. The purpose of this systematic review was to evaluate the effectiveness of acupuncture on clinical pregnancy rates (CPR) after IVF in women with POR. Method(s): Eight electronic databases were searched in January 2020, and reference lists of retrieved articles and previous review articles were hand-searched. Randomized controlled trials (RCTs) using any type of acupuncture for women with POR undergoing IVF were considered. Risk of bias was assessed using the Cochrane risk of bias standards. Result(s): Three RCTs were included in this review. CPR and the number of retrieved oocytes were measured in two studies, while the values of anti-Mullerian hormone (AMH) and antral follicle count (AFC) were only reported in one study. In two studies, CPR was higher in the intervention group than the control group [37.8 % vs 24.3 %]. We did not conduct a meta-analysis, as there was a high level of heterogeneity in interventions among the included trials. Conclusion(s): This study suggests that acupuncture may improve CPR, AMH, AFC and the number of retrieved oocytes in women with POR undergoing IVF. However it is difficult to conclude that acupuncture is more effective than conventional treatment. Additionally, more clinical trials are needed to evaluate the effectiveness of acupuncture on CPR and other outcomes of POR. Study registration: PROSPERO CRD42018087813; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018087813Copyright © 2020

Jang, S. and H. Kim Kyeong (2020). "Clinical Effectiveness and Adverse Events of Bee Venom Therapy: A Systematic Review of Randomized Controlled Trials." Toxins 12(9).
	Bee venom has been used to treat many diseases because of its anti-inflammatory and analgesic effects. However, the secretions of bee venom can also cause life-threatening adverse reactions. The objective of this paper was to review the clinical effectiveness of bee venom and adverse events induced by bee venom, regardless of the disease. Four electronic databases were searched in April 2020. The reference lists of the retrieved articles and previous review articles were also hand-searched. Randomized controlled trials (RCTs) using any type of bee venom other than live bee stings for the clinical treatment of any disease other than cancer were included. The studies were selected, the data were extracted, and the quality of the studies was assessed by two authors. Risk of bias was assessed using the Cochrane risk of bias standards. Twelve RCTs were included in this review-three on Parkinson's disease, four on arthralgia, four on musculoskeletal disorders, and one on polycystic ovary syndrome. The types of bee venom used were acupuncture injections, ultrasound gel, and an ointment. Six studies reported adverse events, and skin reactions such as pruritus and swelling were the most common. The large-scale clinical trials of bee venom therapy are needed to verify the statistical difference, and the reporting system for adverse events is also required to increase the safety of bee venom therapy.

Jang, Y., et al. (2022). "Human Trial for the Effect of Plasma-Activated Water Spray on Vaginal Cleaning in Patients with Bacterial Vaginosis." Medical sciences (Basel, Switzerland) 10(2).
	Underwater plasma discharge temporally produces several reactive radicals and/or free chlorine molecules in water, which is responsible for antimicrobial activity. Hence, it can simply sanitize tap water without disinfectant treatment. Additionally, the spraying technique using cleaning water exploits deep application in the narrow and curved vaginal tract of patients. Herein, we attempted a clinical trial to evaluate the vaginal cleaning effect of spraying plasma-activated water (PAW) to patients with vaginitis (46 patients). The efficacy was compared with treatment with betadine antiseptics used to treat bacterial vaginosis (40 patients). To evaluate the cleaning effect, Gram staining of the vaginal secretions was conducted before and after spraying PAW or betadine treatment (BT). Consequently, PAW-sprayed (PAWS) patients (22.3%) showed a better vaginal cleaning effect against Gram-positive and -negative bacteria than BT patients (14.4%). Moreover, 18 patients in the BT group showed worsened vaginal contamination, whereas five patients in the PAWS group showed worsened vaginal contamination. Taken together, the noncontact method of spraying cleaning water to the vagina exhibited a reliable vaginal cleaning effect without further bacterial infection compared with BT. Therefore, we suggest a clinical application of the spraying method using PAW for vaginal cleaning to patients with vaginitis without disinfectants and antibiotics.

Janicka-Kośnik, M., et al. (2021). "Cervicovaginal Microbiome after Cervical Intraepithelial Neoplasia Treatment. A Protocol for Systematic Review and Meta-Analysis." International Journal of Environmental Research and Public Health 18(17).
	(1) Background: The microbiome consists of microorganisms from various kingdoms with numerous physical and chemical properties Lactobacillus species constitute the highest percentage of healthy cervical and vaginal microbiota. Dysbiosis may cause adverse outcomes, e.g., bacterial vaginosis, pelvic inflammatory disease and pregnancy complications. The cervicovaginal microbiome might contribute to the development of a persistent HPV infection-the main risk factor of cervical cancer-and influence progression to malignancy The aim is to perform a systematic review of current literature and a meta-analysis regarding microbiome changes after cervical intraepithelial neoplasia treatment. (2) Methods: We will search PubMed, Scopus, Google Scholar and Embase Database and trace citations in the reference sections. Randomized and non-randomized controlled studies, case-control and cohort studies published between January 2000 and May 2021 will be included in the study protocol. The following keywords will be used: 'microbiome', 'vaginal microbiome', 'cervical microbiome', 'cervical neoplasia treatment', 'conization', 'electroconization', and 'electrosurgical treatment'. Statistical analyses will be performed using RevMan 5.4. (3) Results: The results will be published as a peer-reviewed article. (4) Conclusions: The study will show which forms of intraepithelial neoplasia treatment change the cervicovaginal microbiome. Finding the best form of treatment by studying the cervicovaginal microbiome after various forms of treatment is essential. Patients would benefit not only from the treatment of the initial disease but also the management of dysbiosis, which might underlie other pathologies.

Janku, F., et al. (2022). "First-in-human study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors." Investigational New Drugs 40(5): 1001-1010.
	Preclinical models suggest anticancer activity of IM156, a novel biguanide mitochondrial protein complex 1 inhibitor of oxidative phosphorylation (OXPHOS). This first-in-human dose-escalation study enrolled patients with refractory advanced solid tumors to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Eligible patients received oral IM156 every other day (QOD) or daily (QD) and were assessed for safety, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary signals of efficacy. 22 patients with advanced cancers (gastric, n = 8; colorectal, n = 3; ovarian, n = 3; other, n = 8) received IM156 100 to 1,200 mg either QOD or QD. There were no DLTs. However, 1,200 mg QD was not well tolerated due to nausea; 800 mg QD was determined as the RP2D. The most frequent treatment-related AEs (TRAEs) were nausea (n = 15; 68%), diarrhea (n = 10; 46%), emesis (n = 9; 41%), fatigue (n = 4; 18%) and abdominal pain, constipation, and blood lactate increased (n = 2 each; 9%). Grade 3 nausea (n = 3; 14%) was the only grade >= 3 TRAE. Plasma exposures increased dose proportionally; mean Day 27 area under the curve (AUC0-24) values were higher following QD administration compared to the respective QOD regimen. Stable disease (SD), observed in 7 (32%) patients (confirmed in 2 [9%]), was the best response. To our knowledge, this is the first phase 1 study of an OXPHOS inhibitor that established a RP2D for further clinical development in cancer. Observed AEs of IM156 were manageable and SD was the best response.Copyright © 2022, The Author(s).

Jannatifar, R., et al. (2022). "Combination of alpha lipoic acid and metformin supplement improve assisted reproductive technologies outcomes in polycystic ovary syndrome patients." Anatomy & cell biology 55(2): 239-246.
	We aimed to investigating the effects of metformin (MET) in combination with alpha lipoic acid (ALA) on hormonal and biochemical parameters, in polycystic ovary syndrome (PCOS) women undergoing intracytoplasmic sperm injection (ICSI). This experimental pilot study with a randomized design was carried out on 40 PCOS women in two groups: (1) MET group, administered 1,500 mg/day MET, and (2) MET (1,500 mg/day)+ALA (1,800 mg/day) group. Drugs were administered from the third day of the previous cycle until the day of oocyte aspiration (six weeks of treatment in total). MET+ALA significantly increased the number of maturated oocytes and the rate of fertilization when compared to the MET group. Combination MET+ALA could increase significantly the number of oocytes retrieval and the number of good-quality embryos. Also, the malondialdehyde (MDA) level decreased significantly in the MET+ALA group and the total antioxidant capacity (TAC) level increased significantly in the MET+ALA group compared to the MET group. Also, fasting blood sugar (FBS), insulin, luteinizing hormone (LH), and LH/follicle stimulating hormone (FSH) levels were significantly lower in the MET+ALA group. The pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, clinical pregnancy, miscarriage, and live births between the control and study groups. The combination of MET+ALA treatment could moderate the complications of PCOS and subsequently improve oocyte and embryo quality.

Jannink, T., et al. (2022). "Long-term pregnancy outcomes in women with normogonadotropic anovulation and clomiphene failure: follow-up study of the M-ovin trial." Human Reproduction 37(Supplement 1): i490-i491.
	Study question: What are the long-term outcomes after gonadotrophins versus clomiphene citrate (CC) with or without intrauterine insemination (IUI) in women with normogonadotropic anovulation and clomiphene failure? Summary answer: The long-term cumulative chance for delivering at least one live birth is 78% for continuing CC and 84% for switching to gonadotrophins. What is known already: CC has long been used as first line treatment for ovulation induction in women with normogonadotropic anovulation, but the best treatment for CC failure was unknown. Between 2009 and 2015, 666 women with normogonadotropic anovulation and CC failure were randomised to gonadotrophins or continued treatment with CC for another six cycles, with or without IUI. Switching to gonadotrophins increased the chance of live birth by 11% over continued treatment with CC after six failed ovulatory cycles, at a cost of e15 258 per additional live birth, while the addition of IUI did not increase live birth rates. Study design, size, duration: We asked women that had been included in the M-ovin trial 6 to 13 years ago for consent to participate in this follow-up study. In the M-ovin trial, 666 women that failed to conceive over 6 ovulatory cycles had been allocated to switching to gonadotrophins versus continuing treatment with CC. Participants/materials, setting, methods: The participating women were asked to complete a web-based questionnaire. The primary outcome of this study was cumulative live birth. Secondary outcomes included fertility treatments, clinical pregnancies, multiple pregnancies, miscarriage, stillbirth, ectopic pregnancy, neonatal outcomes and pregnancy complications. Main results and the role of chance: We managed to contact 570 women of the 666 (85.6%) and retrieved follow-up data for 347 women of whom 176 had been originally allocated to gonadotrophins and 171 to CC. After a median follow-up time of 8 years (range 6-13), 148 women had a live birth (84.1%) in the gonadotrophin group and 133 women had a live birth (77.8%) in the CC group (RR 1.40 95% CI 0.90 - 2.17). A second live birth occurred in 80 of 176 women (45.5%) in the gonadotrophin group and in 77 of 171 women in the CC group (45.0%) (RR 1.01, 95% CI 0.83 - 1.22). A third live birth occurred in 7 of 176 women (4.0%) in the gonadotrophin group and in 11 of 171 women (6.4%) in the CC group. The use of fertility treatments in the follow-up period was comparable between both groups. The number of twin pregnancies were also comparable. Limitations, reasons for caution: In 10.7% of the women, most having a follow-up period above 10 years, contact details had been lost. Therefore, not all eligible women could be approached to participate in this study. It should be realised that preliminary results are presented. Wider implications of the findings: In women with normogonadotropic anovulation and CC failure, continuous treatment with CC for another six cycles is an effective alternative in view of the long-term live birth rates, without the extra costs of gonadotrophins.

Jansen, A., et al. (2023). "Lymphocele following lymph node dissection in cervical and endometrial cancer: A systematic review and meta-analysis." Gynecologic Oncology 170: 273-281.
	Objectives: The purpose of this systematic review and meta-analysis was to evaluate the proportion and risk factors of lymphoceles and symptomatic lymphoceles after PLND in early-stage cervical and early-stage high or high-intermediate risk endometrial cancer.; Methods: Studies reporting on the proportion of lymphocele after PLND were conducted in PubMed, Embase and Cochrane Library. Retrieved studies were screened on title/abstract and full text by two reviewers independently. Quality assessment was conducted using the Newcastle Ottowa Scale and the Cochrane risk-of-bias tool. Proportion of lymphocele and possible risk factors were pooled through random-effects meta-analyses.; Results: From the 233 studies retrieved, 24 studies were included. The pooled proportion of lymphocele was 14% and of symptomatic lymphocele was 3%. Routinely performing diagnostics was associated with a significantly higher proportion of lymphocele compared to diagnostics performed on indication (21% versus 4%, p < 0.01). Laparotomic surgical approach led to a significantly higher proportion of lymphoceles than laparoscopic surgical approach (18% versus 7%, p = 0.05). The proportion of lymphocele was significantly higher when >15% of the study population underwent additional paraaortic lymph node dissection (PAOLND) opposed to <15% (15% versus 3%, p < 0.01). A mean number of lymph nodes dissected of <21 resulted in a significantly higher pooled proportion of lymphoceles opposed to when the mean number was 21 or higher (19% versus 5%, p = 0.02). Other risk factors analysed were BMI, lymph node metastasis, adjuvant radiotherapy and follow up. There was no sufficient data to detect significant risk factors for the development of symptomatic lymphoceles.; Conclusion: The pooled proportion of lymphocele was 14% of which symptomatic lymphoceles occurred in 3%. Significant risk factors for the total proportion of lymphoceles were laparotomic approach, decreased number of lymph nodes dissected and additional PAOLND.; Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.ygyno.2023.01.022. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Jansen Alina, K., et al. (2022). "Tacks vs. sutures: a biomechanical analysis of sacral bony fixation methods for laparoscopic apical fixations in the porcine model." Archives of Gynecology and Obstetrics 305(3): 631-639.
	Purpose: There is a novel surgical procedure, called cervicosacropexy (CESA) and vaginosacropexy (VASA) to treat pelvic organ prolapse and a concomitant urgency and mixed urinary incontinence. As there is little experience with the tapes so far and literature is scanty, the aim of this study was to investigate biomechanical properties for the fixation of the PVDF-tapes with three different fixation methods in context of apical fixations.; Methods: Evaluation was performed on porcine, fresh cadaver sacral spines. A total of 40 trials, divided into 4 subgroups, was performed on the anterior longitudinal ligament. Recorded biomechanical properties were displacement at failure, maximum load and stiffness in terms of the primary endpoints. The failure mode was a secondary endpoint. Group 4 was a reference group to compare single sutures on porcine tissue with those on human tissue. Biomechanical parameters for single sutures on the human anterior longitudinal ligament were evaluated in a previous work by Hachenberg et al. RESULTS: The maximum load for group 1 (two single sutures) was 65 ± 12 N, for group 2 (three titanium tacks arranged in a row) it was 25 ± 10 N and for group 3 (three titanium tacks arranged in a triangle) it was 38 ± 12 N. There was a significant difference between all three groups. The most common failure mode was a "mesh failure" in 9/10 trials for groups 1-3.; Conclusion: The PVDF-tape fixation with two single sutures endures 2.6 times more load than titanium tacks arranged in a row and 1.7 times more load than titanium tacks arranged in a triangle. The presacral fixation with titanium tacks reduced surgical time compared to the fixation with sutures, nevertheless sutures represent the significantly stronger and cheaper fixation method. (© 2021. The Author(s).)

Jaripur, M., et al. (2022). "The effects of magnesium supplementation on abnormal uterine bleeding, alopecia, quality of life, and acne in women with polycystic ovary syndrome: a randomized clinical trial." Reproductive biology and endocrinology : RB&E 20(1): 110.
	Background: Abnormal uterine bleeding (AUB), alopecia, low quality of life, and acne are considered as complications of polycystic ovary syndrome (PCOS). We hypothesized that magnesium supplementation would yield beneficial effects on PCOS related complications.; Objective: To examine the effects of magnesium supplementation on AUB, alopecia, quality of life, and acne.; Methods: In this parallel randomized clinical trial, we randomly assigned 64 women with PCOS to the magnesium group (n = 32) or placebo group (n = 32) for 10 weeks. AUB, alopecia, quality of life, and acne were assessed by the International Federation of Gynecology and Obstetrics criterion, the Sinclair Scale, the Health Survey Quality of Life Questionnaire, and the Global Acne Grading System, respectively. This randomized clinical trial was registered at IRCT.ir (IRCT20130903014551N9).; Results: Magnesium supplementation significantly improved the components of quality of life including physical functioning (p = 0.011), role limitations due to physical health (p = 0.012), role limitations due to emotional problems (p < 0.001), energy/fatigue (p = 0.005), emotional wellbeing (p < 0.001), social functioning (p = 0.002), general health (p = 0.013), and total quality of life (p < 0.001), compared with placebo. No significant effect was observed on acne, alopecia, and AUB.; Conclusion: Magnesium supplementation in women with PCOS had a significant positive effect on improving total quality of life.; Trial Registration: This randomized clinical trial was registered at IRCT.ir on 2020-10-18 (Registration Code: IRCT20130903014551N9 ). (© 2022. The Author(s).)

Javadian, Y., et al. (2023). "Comparison effect of PTNS with biofeedback-assisted pelvic floor muscle training on the frequency of urination and quality of life in women with overactive bladder." Journal of the Neurological Sciences 455(Supplement): 122159.
	Background and aims: The aim of this study was to compare the effect of Percutaneous Tibial Nerve Stimulation (PTNS) with Biofeedback-Assisted Pelvic Floor Muscle Training (BFAPFMT) on quality of life (QoL) and frequency of urination in women with Overactive Bladder (OAB). Method(s): In this clinical trial study, 60 female 18 to 45 years old with OAB were randomly divided into two equal groups. For the first group, BFAPFMT plus kegel exercises was performed 3 times a week for 12 sessions, 15 min exercise. And the second group received PTNS plus kegel exercises 3 times a week for 12 sessions, 15 min exercise +30 min PTNS. The frequency of daily urination (Du) was as the primary outcome. QoL, severity of OAB symptoms, severity of urinary incontinence symptoms(UI), the frequency of nocturnal urination(Nu) and urgency as a secondary outcome were evaluated before, after and one month after the end of the intervention Results: A statistically significant improvement was found in all of study parameters for both groups at the end of the treatment compared with the baseline values except Nu in the BFAPFMT group. The number of Du, severity of UI, urgency and symptoms of OAB in both groups were statistically significantly reduced and consequently QoL in both groups increased. In comparison between groups, a statistically significant difference was observed in the number of Du, Nu and urgency, in favor of PTNS group. Conclusion(s): PTNS and BFAPFMT are two minimally invasive, easy, and cost-effective methods that can significantly reduce the severity of OAB symptoms and increase QoL.Copyright © 2023

Javier, A. T., et al. (2022). "Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist controlled ovarian stimulation: a systematic review."
	
Jayakumaran, J., et al. (2023). "Monofilament vs multifilament suture for cervical cerclage: a multicenter randomized controlled trial." American Journal of Obstetrics & Gynecology MFM 5(2): 100823.
	
Jayasena Channa, N., et al. (2019). "A systematic review of randomized controlled trials investigating the efficacy and safety of testosterone therapy for female sexual dysfunction in postmenopausal women." Clinical Endocrinology 90(3): 391-414.
	The clinical sequelae of oestrogen deficiency during menopause are undoubted. However, the pathophysiological role of testosterone during the menopause is less clear. Several randomized, placebo-controlled clinical trials suggest that testosterone therapy improves sexual function in postmenopausal women. Some studies suggest that testosterone therapy has additional effects, which include increased bone mineral density and decreased serum high-density lipoprotein (HDL) cholesterol. Furthermore, the long-term safety profile of testosterone therapy in postmenopausal women is not clear. This article will provide a concise and critical summary of the literature, to guide clinicians treating postmenopausal women. (© 2018 John Wiley & Sons Ltd.)

Jeans, E. B., et al. (2021). "Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(6): 859-867.
	OBJECTIVES: Optimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy. METHODS: From April 1998 to January 2020, women with FIGO stage IA-IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes. RESULTS: A total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3-12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology. CONCLUSION: Adjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

Jefford, E., et al. (2023). "The impact of abortion doulas on women and providers' outcomes: An integrative review of the evidence." Sexual & reproductive healthcare : official journal of the Swedish Association of Midwives 37: 100888.
	The aim of this integrative review is to map the literature on the impact of abortion doulas on women and abortion care providers. This review followed a modified Whittemore and Knafl framework and PRISMA guidelines. Electronic databases (Medline, PubMed, CINAHL, the Cochrane Library, Scopus, Proquest, EMBASE, and PsycINFO) were searched using key terms: abortion and doula. Search was limited by date (2012-2022), type (primary research only), and language (English only). Of the 99 papers found, only 4 met inclusion criteria. The four papers - drawn from 2 studies - were analysed using NICE Appraisal checklists. In total, data from 328 participants (n = 314 women, n = 5 physicians, n = 5 staff members, n = 4 abortion doulas) was analysed. Of the 314 women, 160 women received doula support and 154 did not. Two qualitative papers showed women and abortion providers reported a beneficial impact of abortion doulas, but the two quantitative (RCTs) papers showed null impact for a doula support intervention vs. usual care on women's physical and psychological outcomes. Women reported wanting support during the abortion; however, the evidence is not yet clear on whether a doula is required to address this need for women undergoing a surgical abortion in clinic. It may be that abortion support is important in ways that are difficult to measure.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Jeffrey, L. and PsyD (2022). "A Brief, Transdiagnostic Cognitive Behavioral Treatment for Urological Chronic Pelvic Pain Syndrome: Processes, Predictions, Outcomes." ClinicalTrials.gov.
	Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated. Their prolonged personal and economic costs are amplified by the frequent co-occurrence of a cluster of centralized pain conditions (particularly irritable bowel syndrome 3 \[IBS\]) but also fibromyalgia \[FMS\], chronic headache, chronic fatigue, etc.) called Chronic Overlapping Pain Conditions (COPC). Clinically, the notion that these syndromes share a centralized pain phenotype with a fundamental disturbance in pain or sensory processing dovetails with our preliminary research showing that a novel transdiagnostic behavioral treatment emphasizing a single common mechanistic pathway (i.e. inflexible cognitive style) reduces severity of both targeted (IBS) and untargeted multisymptom COPCs that include (but is not limited to) to UCPPS, FMS, chronic fatigue, and chronic headache. If effective in a larger scale study, a transdiagnostic UCPPS treatment would offer a more efficient, accessible, and broadly useful strategy for improving chronic pelvic pain and its most frequent and complicating comorbidities. To this end, the investigators will randomize 240 UCPPS subjects (18-70 yrs.) of any gender and race to a 4-session version of CBT that teaches skills for self-managing UCPPS symptoms (e.g. pelvic pain, urinary symptoms such as urinary frequency, urgency) with minimal clinician oversight (MC-CBT) or a four-session non-specific education/support control (EDU). Efficacy assessments will be administered at pre-treatment baseline and two weeks after the end of the 10-week acute phase using the patient version of the Clinical Global Impressions Scale and validated with the physician version rated by MD assessors blind to treatment assignment. The investigators hypothesize MC-CBT will deliver significantly greater UCPPS symptom improvement than EDU (Aim 1). Additional aims include characterizing the durability of effects 3- and 6 months post treatment (Aim 2). To increase the efficacy and efficiency of behavioral pain treatments, the investigators draw upon Beck\'s transdiagnostic cognitive model to characterize the precise cognitive procedures and corresponding operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC-CBT induced UCPPS symptom relief relative to EDU (Aim 3) as well as baseline patient variables that moderate differential response (Aim 3) with the ultimate goal of more proactive patient-treatment matching fundamental to the goals of personalized medicine. By applying innovative statistical modelling (e.g. dominance analysis, Randomized Explanatory Trial analyses) to study aims in the context of a rigorously designed behavioral trial, the researchers expand the portfolio of nondrug pain treatments for UCPPS and co-aggregating COPCs to include one whose brevity, convenience, and transdiagnostic design \"meets patients where they are\" and addresses the practical (access, complexity, cost), clinical (breadth, durability, magnitude of effects, patient preference) and conceptual (untargeted comorbidities, non-pain somatic symptoms) challenges that have impeded uptake and public health impact of evidence-based behavioral pain treatments at a time when our most vulnerable high impact pain patients are in greatest need.

Jegaden, M., et al. (2023). "Innovations in surgery to perform an ovarian drilling." Journal of Gynecology Obstetrics and Human Reproduction 52(1): 102499.
	Background: Ovarian drilling is a surgical technique for patients with dysovulatory polycystic ovarian syndrome. It is proposed as a second-line treatment in case of failure of medical treatment with Clomiphene citrate, Metformin or Letrozole. The 2020 Cochrane study comparing gonadotrophin stimulation and drilling has found the same pregnancy rate in both cases. The literature review concludes that 50% of spontaneous ovulation occurs in the first three months after drilling and 80% of pregnancy occurs in the following year. Ovarian drilling has also an impact on androgen excess and metabolic syndrome. Aim(s): To update on the different surgical techniques to perform an ovarian drilling: surgical approach, energy used, operative risks. Techniques: The objective of an ovarian drilling is to destroy 5% of the ovarian stroma. It is recommended to perform 8 to 10 perforations in each ovary with bipolar energy. Laser C02 and monopolar energy can be used but increase the risk of adhesion. The surgical approach is actually laparoscopic. Abdominal laparoscopy or transvaginal laparoscopy by vNOTES can be performed. The advantage of the second one is to provide an easier access to the pelvic cavity in case of obesity and patient have no abdominal scare. Both laparoscopic approaches allow an evaluation of tubal patency and adhesiolysis or fimbrioplasty. That it's not the case of an alternative technique: the fertiloscopy, due to coaxial instrumentation in spite of less rate of post-operative adhesions. Operative risks are abdominal adhesions, damage to neighboring organs and due to the general anesthesia. Conclusion(s): Different surgical techniques exist to perform an ovarian drilling. The surgeon can choose the one that he masters best and that will involve the least risk for the patient. It is recommended to use bipolar energy.Copyright © 2022 Elsevier Masson SAS

Jensen, M. C., et al. (2021). "Hormonal contraceptive use and depression." Cochrane Database of Systematic Reviews(1).
	- Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The objective of this review is to assess risk of depression in fertile women with use versus non‐use of hormonal contraceptives. Furthermore, this review will perform a direct comparison of risk of depression, use of antidepressants, generalised anxiety disorder, alcohol/cigarette/drug consumption, and suicide attempts or suicide associated with different hormonal contraceptives depending on generation of progestogen and dose of oestrogens.

Jensterle, M., et al. (2022). "Semaglutide delays 4-hour gastric emptying in women with PCOS and obesity." Diabetes, Obesity & Metabolism.
	CONTEXT: Semaglutide could contribute to reduced energy intake and weight loss by delaying gastric emptying (GE). However, the evidence for notable effects of semaglutide is inconclusive and compromised by the use of indirect methodology. OBJECTIVE: to evaluate the effect of once-weekly subcutaneous semaglutide 1.0 mg on late digestive period of GE after ingestion of a standardized solid test meal by using technetium scintigraphy, the reference method for this purpose. DESIGN: We conducted single-blind, placebo-controlled trial with 20 obese women with PCOS (average age 35 (32.3-40.8) years), BMI 37 (30.7-39.8) kg/m2 ) randomized to s.c semaglutide 1.0 mg QW (S) or placebo (P) for 12 weeks. GE was assessed after ingestion of [99mT c] colloid in pancake labeled with radiopharmaceutical by scintigraphy using sequential static imaging and dynamic acquisition at baseline and at week 13. Estimation of GE was obtained by repeated imaging of remaining [99mT c] activity (RA) at fixed time intervals over 4 hours after ingestion. RESULTS: From baseline to the study end, semaglutide increased the estimated retention of gastric contents by 3.5% at the 1st hour, 25.5% at 2nd , 38.0% at 3rd and 30.0% at the 4th hour after ingestion of the radioactively labeled solid meal. Four hours after ingestion, semaglutide retained 37% of solid meal in the stomach compared to no gastric retention in P group (p=0.002). Half time (T1/2 ) was significantly longer in S as compared to P (171 min vs 118 min, (p<0.001). CONCLUSION: Semaglutide markedly delayed 4-hour GE in women with PCOS and obesity. This article is protected by copyright. All rights reserved.

Jensterle, M., et al. (2022). "Once-weekly semaglutide delays a late phase gastric emptying of solid meal measured by repeated scintigraphic imaging in obese women with PCOS." Journal of the Endocrine Society 6(Supplement 1): A33-A34.
	Background: GLP-1 agonism have the potential to affect gastric emptying (GE), yet the reports for subcutaneous semaglutide, currently the most effective GLP-1 RA approved for weight management, remain inconclusive. It has been demonstrated that once-weekly semaglutide either had no effect on GE or it delayed GE only within the first hour, without late phase retention. Notably, those conclusions were made by an indirect method of estimation of GE through ingestion, absorption and determination of plasma level of paracetamol. Furthermore, in most previous studies with once weekly semaglutide, GE has been evaluated as a part of the composite outcome. The indirect method with paracetamol was shown to be appropriate for evaluation of kinetics of liquid meals, whereas it might lead to inaccurate estimation of late phase GE. Scintigraphic evaluation is considered as a reference method for the purpose. Aim(s): This is the first study that evaluates the effect of once weekly subcutaneous semaglutide on late phase GE of a solid meal by scintigraphy in obese women with PCOS without other comorbidities as a primary outcome. Material(s) and Method(s): A single-blind, placebo-controlled trial was conducted in 20 women with PCOS and obesity, without diabetes and other comorbidities, randomized to once weekly subcutaneous semaglutide 1 .0 mg (S) or placebo (P) for 8 weeks. Gastric emptying was assessed by scintigraphy after ingestion of 99mTC colloid in pancake labelled with radiopharmaceutical that maintained a stable binding within gastric environment by scintigraphy using sequential static imaging and dynamic acquisition. Estimation of GE was obtained by repeated imaging of remaining 99mTC activity (RA) at fixed time intervals over 4 hours and the half time (T1/2) of gastric emptying had been calculated. Additionally, we evaluated anthropometric, metabolic, hormonal and appetite parameters. Result(s): At 30 min after ingestion significant difference in RA was observed between semaglutide group and placebo (92.5% in S vs. 89% in P (p=0,05)) and persisted throughout the observation period up to 4 hour (37% in S vs. 0% in P (p=0,002)). T1/2 was significantly longer in S as compared to P (171 min vs 118 min, respectively (p<0.001)). In addition, semaglutide led to significant decrease in weight, waist and neck circumference, HbA1c and androgen levels. Subjective ratings of appetite suppression correlated with T1/2. Conclusion(s): Once weekly semaglutide 1.0 mg resulted in a significant late-phase retention of solid meal measured by repeated scintigraphic imaging. This effect correlated with appetite suppression and likely contributed to weight loss.

Jeon Myung, J., et al. (2020). "Non-absorbable versus absorbable sutures for anterior colporrhaphy: study protocol for a randomised controlled trial in South Korea." BMJ Open 10(6): e034218.
	Introduction: The anterior vaginal wall is the segment most commonly affected by prolapse. Traditionally, anterior vaginal wall prolapse is repaired via anterior colporrhaphy, which is known to have a high recurrence rate. Several factors might affect the outcome of anterior colporrhaphy, and the use of absorbable sutures might also be associated with the high recurrence rate because the sutures might not be able to retain adequate strength until the plicated pubocervical fascia remodels and regains maximum tensile strength. Nonetheless, no comparative data exist about the relative efficacy and safety of anterior colporrhaphy using non-absorbable versus absorbable sutures. The objective of this study is to compare the surgical outcomes of anterior colporrhaphy using non-absorbable sutures with those of anterior colporrhaphy using absorbable sutures.; Methods and Analysis: This is a randomised, multicentre, superiority trial. Anterior colporrhaphy will be performed in a traditional manner with midline plication of the fibromuscular layer using either non-absorbable or absorbable sutures. The primary outcome is composite surgical success 1 year after surgery defined as the absence of all of the following: (1) anterior vaginal descent beyond the hymen, (2) the presence of vaginal bulge symptoms and (3) retreatment for recurrent anterior vaginal wall prolapse with either surgery or pessary. The secondary outcomes include the individual components of the composite primary end point, anatomical outcomes, condition-specific quality of life and adverse events related to anterior colporrhaphy. The planned number of participants is 192.; Ethics and Dissemination: This study was approved by the Institutional Review Board of Seoul National University Hospital (H-1810-037-977). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.; Trial Registration Number: NCT03736811.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Jeong, C., et al. (2023). "Effects of Bazedoxifene/Vitamin D Combination Therapy on Serum Vitamin D Levels and Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized Controlled Trial." Journal of Bone Metabolism 30(2): 189-199.
	Background: This study aimed to evaluate the effectiveness of bazedoxifene/vitamin D combination therapy in preventing osteoporosis in postmenopausal women with osteopenia. Method(s): This was an open-label, multicenter randomized-controlled, phase 4 clinical trial. Women between ages of 55 and 70 years in 9 medical tertiary centers in Korea were enrolled and assigned into 2 groups: an experiment group and a control group. The experimental group received bazedoxifene 20 mg/vitamin D 800 IU tablets for 6 months, and the control group received calcium 100 mg/vitamin D 1, 000 IU tablets for 6 months. Result(s): A total of 142 patients (70 in the experimental group and 72 in the control group) were included. The least-square mean+/-standard error of change in propeptide of type I collagen after 3 months was -6.87+/-2.56% in the experimental group and 1.22+/-2.54% in the control group. After 6 months, it was -21.07+/-2.75% in the experimental group and 1.26+/-2.71% in the control group. The difference between the 2 groups was -22.33% (P<0.01). The change of C-terminal telopeptide was -12.55+/-4.05% in the experimental group and 11.02+/-4.03% in the control group after 3 months. It was -22.0+/-3.95% and 10.20+/-3.89, respectively, after 6 months. The difference between the 2 groups was -32.21% (P<0.01) after 6 months. There was no significant difference in adverse events between the 2 groups. Conclusion(s): The osteoporosis preventive effect and safety of administering bazedoxifene/vitamin D combination pill were confirmed in postmenopausal women who needed osteoporosis prevention.Copyright © 2023 The Korean Society for Bone and Mineral Research.

Jeong, H. S., et al. (2020). "Mesonephric-like carcinoma of the uterine corpus: A case report and literature review." Eur. J. Gynaecol. Oncol. 41(5): 664-667.
	
Jeong Young, J., et al. (2023). "Impact of Acupuncture on Hot Flashes in Breast Cancer Patients Receiving Adjuvant Antiestrogen Therapy with Tamoxifen: A Randomized Controlled Trial." Journal of Integrative and Complementary Medicine 29(4): 241-252.
	Objectives: The aim of this study was to evaluate the impact of acupuncture on hot flashes in breast cancer patients taking tamoxifen as an adjuvant antiestrogen therapy in Korea. Design: This trial was a randomized, no-treatment-controlled, single-blind, multi-center trial. Participants were randomized 1:1 into the acupuncture group or into the no-treatment control group. Location: This trial was conducted at Daegu Catholic University Hospital and Daegu Haany University Korean Medicine Hospital in Daegu, Republic of Korea. Participants: Patients with moderate to severe symptoms of hot flashes while receiving adjuvant antiestrogen therapy using tamoxifen after surgery for breast cancer were included. Interventions: In the acupuncture group, acupuncture was performed three times a week for 4 consecutive weeks at five predetermined points. The control group received no treatment during the study period. Study Outcome Measures: As a primary outcome, the severity of hot flashes was measured on the visual analogue scale (VAS) and total hot flash score. In addition, the quality of life (QoL) of participants was assessed as a secondary outcome. Results: A total of 30 patients were included in this study, 15 each in the acupuncture group and the control group. The participants in the acupuncture group significantly decreased the severity of hot flashes evaluated with both VAS and total hot flash scores compared with participants in the control group. Also, the acupuncture group showed improved score of a global health status/QoL scale and functional scales assessed with the European Organisation for Research and Treatment of Cancer QoL questionnaire-core questionnaire, compared with those in the control group. This trend was maintained 4 weeks after acupuncture treatment. No adverse events have been reported in this study. Conclusions: Acupuncture was effective and safe in improving hot flashes in Korean breast cancer patients receiving adjuvant antiestrogen therapy with tamoxifen, and it improved the QoL. Clinical Trial Registration: KCT0007829.

Jeppson, P. C. (2021). "A systematic review on the use of misoprostol at the time of open myomectomy [commentary]." BJOG: An International Journal of Obstetrics and Gynaecology 128(3): 484.
	This is a mini commentary on S Wali et al., pp. 476–483 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.16389

Jepsen Ida, E., et al. (2022). "Probiotic treatment with specific lactobacilli does not improve an unfavorable vaginal microbiota prior to fertility treatment-A randomized, double-blinded, placebo-controlled trial." Frontiers in Endocrinology 13: 1057022.
	Objective: To investigate whether treatment with proprietary lactobacilli-loaded vaginal capsules improves an unfavorable vaginal microbiome diagnosed using a commercially available test and algorithm.; Design: A randomized, double-blinded, placebo-controlled study was conducted in 74 women prior to undergoing fertility treatment at a single university fertility clinic between April 2019 and February 2021. The women were randomly assigned in a 1:1 ratio to receive one vaginal capsule per day for 10 days containing either a culture of more than 10 8 CFU of Lactobacillus gasseri and more than 10 8 CFU Lactobacillus rhamnosus (lactobacilli group) or no active ingredient (placebo group). Vaginal swabs for microbiota analysis were taken at enrollment, after treatment and in the cycle following treatment.; Participants and Methods: Women aged 18-40 years who prior to fertility treatment were diagnosed with an unfavorable vaginal microbiota, characterized by either a low relative load of Lactobacillus or a high proportion of disrupting bacteria using the criteria of the IS-pro™ diagnostic system (ARTPred, Amsterdam, the Netherlands), were enrolled in the study. The primary outcome measure was the proportion of women with improvement of the vaginal microbiota after intervention.; Results: The vaginal microbiota improved after intervention in 34.2% of all participants (lactobacilli group 28.9%, placebo group 40.0%), with no significant difference in the improvement rate between the lactobacilli and placebo groups, RR = 0.72 (95% CI 0.38-1.38).; Conclusion: This study indicates that administering vaginal probiotics may not be an effective means of modulating the vaginal microbiome for clinical purposes in an infertile population. However, a spontaneous improvement rate of 34.2% over a period of one to three months, confirming the dynamic nature of the vaginal microbiota, indicates that a strategy of postponing further IVF treatment to await microbiota improvement may be relevant in some patients, but further research is needed.; Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03843112.; Competing Interests: MW reports a personal fee from Merck for a lecture. NM reports consultancy fees from ARTPred. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Jepsen, Saxtorph, Englund, Petersen, Wissing, Hviid and Macklon.)

Jéssica, T., et al. (2021). "Effects of metformin treatment on androgenic hormone levels in patients with Polycystic Ovary Syndrome: a systematic review and meta-analysis of randomized controlled trials."
	
Jester, J. M., et al. (2023). "Randomized pilot trial of the "Mom Power" trauma- and attachment-informed multi-family group intervention in treating and preventing postpartum symptoms of depression among a health disparity sample." Frontiers in Psychiatry 14: 1048511.
	Introduction: Perinatal depression, a common complication related to childbearing, impacts mothers, children, and families. Efficacious interventions reduce perinatal depression symptoms; effort is needed to prevent the onset of perinatal depression. To determine feasibility and preliminary efficacy in reducing perinatal depression, we conducted a community-based, randomized parallel open pilot trial of Mom Power, a group-based intervention to improve mental health and parenting in mothers with young children. Method(s): Mom Power consists of 10 group sessions, focused on parenting, child development and self-care and three individual sessions, to build rapport and provide personalized referrals. Control group participants received psychoeducational mailings. Computer-based urn randomization assigned mothers with experiences of interpersonal violence, depression, or other traumatic experiences to Mom Power (68) or control (54). Result(s): At 3-months post-treatment, the 31 retained women assigned to Mom Power were half as likely to meet criteria for probable depression (26%) as the 22 women retained in the control group (55%), with treatment predicting lower incidence of probable depression (OR = 0.13, p = 0.015). Moreover, among the 23 women who did not meet criteria for depression diagnosis at baseline, no women in the treatment group developed depression (n = 0, 0%) compared to control group women (n = 3, 30%). Logistic regression controlling for selective attrition confirmed the treatment effect on preventing new onset of depression (OR = 0.029, p = 0.012). Conclusion(s): These findings support the use of Mom Power for both treatment and prevention of perinatal depression. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT01554215, NCT01554215.Copyright © 2023 Jester, Riggs, Menke, Alfafara, Issa, Muzik and Rosenblum.

Jethaliya, H., et al. (2022). "Efficacy of Myo-inositol on Anthropometric, Metabolic, and Endocrine Outcomes in PCOS Patients: a Meta-analysis of Randomized Controlled Trial." Reproductive sciences (Thousand Oaks, Calif.) 29(8): 2282-2298.
	Polycystic ovary syndrome (PCOS) is a common cause of female infertility, affecting 5-10% of women of reproductive age. Many studies have reported improvement in insulin resistance and thereby intracellular glucose uptake after myo-inositol treatment in PCOS patients, but these studies have a small sample size, varying methodology, and outcome analysis. Therefore, we designed a present meta-analysis of randomized controlled trials to explore the effect of myo-inositol supplementation on anthropometric, metabolic, and endocrine outcomes in PCOS patients. Randomized controlled trials assessing the effectiveness of myo-inositol were identified in electronic databases like PubMed, Cochrane, Embase, MEDLINE, CINAHL, and AMED. Listed references and citations of related articles were also screened manually to identify additional studies. Research papers for which full-text copies were not available on scientific databases were procured from respective authors. Thereafter, data were extracted from included studies and analyzed using RevMan 5.3 of the Cochrane Collaboration. A total of 17 randomized controlled trials with 1083 PCOS patients were included in this meta-analysis. Among the 17 trials, 7 trials compared myo-inositol with folic acid, 8 trials compared myo-inositol with metformin, and 2 trials compared myo-inositol with oral contraceptives. No significant improvement in body mass index, waist-to-hip ratio, fasting insulin, fasting glucose, HOMA, LH, FSH, estradiol, sex hormone-binding globulin, dehydroepiandrosterone, and total testosterone levels were observed after myo-inositol treatment in PCOS patients except androstenedione and prolactin levels. Clinically significant improvement was not observed in anthropometric, metabolic, and endocrine outcomes after myo-inositol treatment in PCOS patients. However, heterogeneity between studies was high. (© 2022. Society for Reproductive Investigation.)

Jha, A. K. and N. Jha (2023). "Ketamine Compared With Fentanyl for Surgical Abortion: a Randomized Controlled Trial." Obstetrics and Gynecology 141(1): 226.
	
Jha, S., et al. (2024). "Management of mixed urinary incontinence: IUGA committee opinion." International Urogynecology Journal 35(2): 291-301.
	Introduction and hypothesis: Mixed urinary incontinence (MUI) is defined by the International Urogynecology Association (IUGA) and International Continence Society as the complaint of involuntary leakage of urine associated with urgency and also with exertion, effort, sneezing or coughing. It therefore implies the coexistence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). MUI is a heterogeneous diagnosis that requires an assessment of its individual components of SUI and UUI. Management requires an individualised approach to the symptom components. The aim of this review is to identify the assessment/investigations and management options for MUI. Method(s): A working subcommittee from the IUGA Research & Development (R&D) Committee was created and volunteers invited from the IUGA membership. A literature review was performed to provide guidance focused on the recommended assessment and management of MUI. The document was then evaluated by the entire IUGA R&D Committee and IUGA Board of Directors and revisions made. The final document represents the IUGA R&D Committee Opinion. Result(s): The R&D Committee MUI opinion paper provides guidance on the assessment and management of women with MUI and summarises the evidence-based recommendations. Conclusion(s): Mixed urinary incontinence is a complex problem and successful management requires alleviation of both the stress and urge components. Care should be individualised based on patient preferences. Further research is needed to guide patients in setting goals and to determine which component of MUI to treat first. The evidence for many of the surgical/procedural treatment options for MUI are limited and needs to be explored in more detail.Copyright © The Author(s) 2024.

Ji, H., et al. (2023). "The Impact of Mismatch Repair Status in immune-checkpoint inhibitor combined with chemotherapy in advanced or recurrent endometrial cancer."
	
Ji Hae, R., et al. (2020). "Herbal medicine (Taohong Siwu Tang) for the treatment of primary dysmenorrhea: A systematic review and meta-analysis." Explore (New York, N.Y.) 16(5): 297-303.
	Objectives: This systematic review aimed to evaluate the efficacy and safety of Tao-Hong Siwu Tang (TST) for the treatment of primary dysmenorrhea.; Methods: We searched four English databases (MEDLINE, EMBASE, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials [CENTRAL, Cochrane Library]), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Periodical Database), two Korean databases (Oriental Medicine Advanced Searching Integrated System and Korean traditional Knowledge Portal), and one Japanese database (Citation Information by NII). All randomized controlled trials (RCTs) using TST or modified TST (MTST) were included. Three independent reviewers extracted the data, assessed the risk of bias according to the Cochrane criteria, and performed a meta-analysis.; Results: A total of 85 possibly relevant articles were identified, and five trials met our inclusion criteria. The meta-analysis showed a favorable effect of MTST compared to non-steroidal anti-inflammatory drugs (NSAIDs) (n = 486, risk ratio [RR] = 1.53, 95% confidence interval [95% CI] = 1.37-1.72, I 2 = 39%). Among the included trials, one RCT showed superior effects of MTST on primary dysmenorrhea recurrence rate compared to NSAIDs (n = 246, RR = 0.31, 95% CI = 0.15-0.63, P = 0.001). Another RCT revealed a beneficial impact of oral contraceptives (OCs) used in combination with TST compared to OCs alone (n = 60, RR = 1.35, 95% CI = 1.02-1.79, P = 0.04).; Conclusion: This systematic review and meta-analysis provides moderate quality evidence for the superiority of MTST over NSAIDs as well as that of TST plus OCs over OCs in the treatment of primary dysmenorrhea.; Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. (Copyright © 2020. Published by Elsevier Inc.)

Ji, M., et al. (2022). "Efficacies of FAEV and EMA/CO regimens as primary treatment for gestational trophoblastic neoplasia." British Journal of Cancer 127(3): 524-530.
	Background: Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic neoplasia (GTN). However, the floxuridine, actinomycin D, etoposide and vincristine (FAEV) regimen is commonly used to treat these patients in China. We conducted a randomised controlled trial to compare the efficacies and toxicities of FAEV and EMA/CO. Method(s): Ninety-four patients with GTN were enrolled between May 2015 and April 2019 and randomly assigned to the FAEV or EMA/CO regimen. The rates of complete remission and relapse and the toxicities were compared in August 2021. Result(s): Five patients were excluded from the analysis. There were 46 patients in the FAEV group and 43 patients in the EMA/CO group. The complete remission rates following primary treatment were 89.1% and 79.1% (P = 0.193), respectively. The relapse rates were 8.7% and 9.3% (P = 0.604). The apparent incidences of grade 4 myelosuppression were 60.9% and 32.6% (P = 0.008), respectively; however, they became both 32.6% (P = 0.996) after granulocyte colony-stimulating factor support. Other adverse reactions were similar in the two groups. No patient died of disease. Conclusion(s): FAEV has comparable efficacy and toxicity to EMA/CO as the primary treatment for high-risk GTN, and may thus be another first-line choice of chemotherapy. Clinical trial registration: chictr.org.cn: ChiCTR1800017423.Copyright © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

Ji, M., et al. (2024). "Meta-analysis of the effect of different exercise modalities in the prevention and treatment of perinatal depression." Journal of Affective Disorders 350: 442-451.
	Background: The incidence of perinatal depression is increasing and has become a global public health problem to be addressed. Objective(s): To explore the prevention and treatment effects of different exercise methods on perinatal depression. Method(s): A meta-analysis was conducted by searching databases for published "exercise interventions for perinatal depression "related randomized controlled trials, up to July 20, 2022. Result(s): 48 randomized controlled trials were included, with a total of 5282 pregnant women. (1) Exercise prevention of prenatal depression has a low effective stress intervention effect, ranking from high to low as yoga, aerobic+resistance. (2) Exercise therapy for prenatal depression has a significant intervention effect, followed by gymnastics, pelvic floor muscle training, aerobic exercise, aerobic+resistance, and yoga. (3) Exercise prevention of postpartum depression has a low effective intervention effect, followed by yoga, aerobic exercise, aerobic+resistance, and gymnastics. (4) Exercise has a moderate equivalent stress intervention effect on treating postpartum depression, followed by aerobic exercise, water exercise, yoga, fertility dance, and stroller walking. Limitation(s): Due to the small number of included literature on single exercise modalities, and maternity is a special population, most of the trial procedures included in the text were not blinded, which has a certain risk of bias and affects the accuracy of the Meta-analysis results. Conclusion(s): The therapeutic effect of exercise in the prevention and treatment of perinatal depression is superior to the preventive effect, and the effect of prenatal prevention and treatment is better than that of postpartum, with a moderate effect.Copyright © 2024

Ji, X., et al. (2022). "Effect of probiotics combined with metformin on improvement of menstrual and metabolic patterns in women with polycystic ovary syndrome: a randomized clinical trial." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(10): 856-860.
	Objectives: The aim of this study was to access the efficacy of probiotics combined with metformin on improvement of menstrual and metabolic patterns in women with polycystic ovary syndrome (PCOS). Methods: In this single-centre, controlled, randomized clinical trial (NCT03336840), 60 non-obese women with PCOS were randomly assigned (1:1:1) to receive probiotics (4 g daily), metformin (1.5 g daily) or their combination for 12 weeks. The primary outcome was the improvement of menstrual patterns. The secondary outcomes included changes in anthropometric, metabolic profiles and hormonal levels. Results: After 12-week treatment, the recovery rate of menstrual cycle was 40% in probiotics group, 55% in metformin group and 80% in combination group ( p = 0.035). Meanwhile, the ovulation rate was 30% in probiotics group, 55% in metformin group and 75% in combination group ( p = 0.017). Serum anti-Müllerian hormone, testosterone, free androgen index, BMI, fasting blood glucose, HOMA-IR, lipid profiles were decreased after probiotics or metformin treatment in non-obese women with PCOS. Conclusion: In the present trial, probiotics combined with metformin was superior to probiotics or metformin alone to improve menstrual patterns in women with PCOS. Metabolic and hormonal profiles were also improved after probiotics or metformin treatment.

Jia, W., et al. (2023). "Long-term effects of bipolar electrocoagulation and suture hemostasis on the ovarian reserve following endometriotic cystectomy: a meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Jia, W. and L. Tao (2021). "Effect of Yishen Huoxue Recipe on uterine recovery and intrauterine adhesion in patients after general anesthesia induced abortion." 陕西中医 42(8): 1080‐1083.
	Objective: To analyze the effect of Yishen Huoxue Recipe on uterine recovery and intrauterine adhesion in patients after general anesthesia induced abortion. Methods: 166 patients after induced abortion under general anesthesia were randomly divided into control group and observation group with 83 cases in each group. The control group was treated with estradiol valerate tablets, estradiol valerate tablets/estradiol cyproterone valerate, and the observation group was treated with Yishen Huoxue prescription on the basis of the control group. week. The time of menstrual rehydration and the occurrence of clinical symptoms in the two groups were observed, and the serum matrix metalloproteinase (MMP) levels, endometrial resistance index (RI), blood flow parameters (PI) and blood flow parameters (PI) were compared between the two groups before treatment and after two weeks of treatment. Endometrial thickness, intrauterine adhesion score. Results: During the treatment period, the proportion of patients with low menstrual flow in the observation group (2.41%) was significantly lower than that in the control group (13.25%, P<0.05). Compared with before treatment, after two weeks of treatment, the serum levels of matrix metalloproteinase‐2 (MMP‐2), matrix metalloproteinase‐3 (MMP‐3), and matrix metalloproteinase‐9 (MMP‐9) in the two groups were increased. The group was higher than the control group (P<0.05). Compared with before treatment, after two weeks of treatment, the endometrial thickness in the observation group was thicker and thicker than that in the control group (P<0.05). . Compared with before treatment, after two weeks of treatment, the menstrual condition, adhesion range and adhesion type scores in the two groups decreased, and the observation group was lower than the control group (P<0.05). Conclusion: Yishen Huoxue Recipe can effectively promote menstrual recovery and uterine recovery in patients after general anesthesia and induced abortion, promote the increase of uterine serum MMP‐2, MMP‐3 and MMP‐9 levels, and effectively reduce the risk of intrauterine adhesions. better treatment effect.

Jia, X., et al. (2022). "Cost-Effectiveness Analysis: Autologous Rectus Fascial Sling versus Retropubic Midurethral Sling for Female Stress Urinary Incontinence." International Urogynecology Journal 33(Supplement 2): S495-S496.
	Introduction: Surgeries for female stress urinary incontinence can be divided into mesh and non-mesh procedures. One of the most commonly performed mesh procedures is retropubic midurethral sling. Non-mesh procedures include pubovaginal sling, Burch and urethral bulking. Current controversies involving mesh procedures have led to a recurrent interest in non-mesh treatments. Pubovaginal sling has similar effectiveness as midurethral sling but different rates of complications. Limited data exist on the cost effectiveness between midurethral sling and pubovaginal sling. Objective This study aims to evaluate the cost-effectiveness of autologous rectus fascial sling (ARFS) to retropubic midurethral sling (RMUS) from both hospital and healthcare perspectives. Method(s): A decision tree model comparing the costs and effectiveness between ARFS and RMUS was developed. The model was based on 1 year of follow-up. We included the following variables in the model: objective success rate, rates of complications, subsequent treatments for complications, and retreatment for stress urinary incontinence. The model included the index procedure and one retreatment for subjects who had persistent stress urinary incontinence. Cost estimates were calculated from both hospital system and healthcare payer perspectives. The outcomes from the model were expressed in incremental cost-effectiveness ratio (ICER), or cost per quality-adjusted life year (QALY). An ICER of less than $50,000 per QALY was considered cost-effective. Result(s): From the hospital perspective, the overall cost of retropubic midurethral sling was higher than autologous rectus fascial sling ($2,348.94 vs. $2,114.06), but was more effective (0.82 vs. 0.80 QALYs). The incremental cost-effectiveness ratio was $17,622 per quality-adjusted life year, which was below the threshold of $50,000/ QALY. From a healthcare perspective, the overall cost of autologous rectus fascial sling was higher than retropubic midurethral sling ($4,656.63 vs. $4,630.47) while also being less effective. Retropubic midurethral sling was thus the dominant strategy. Sensitivity analyses showed that the overall cost of retropubic midurethral sling surgery and the success rate of autologous rectus fascial sling had an impact on the incremental cost-effectiveness ratio. If the overall cost of retropubic midurethral sling surgery exceeds $2654.36, it would no longer be considered cost-effective compared to autologous fascial sling at a willingness-to-pay threshold of 50,000/QALY. Similarly, if the success rate of autologous rectus fascial sling exceeds 84.39%, autologous rectus fascial sling would become cost-effective compared to retropubic midurethral sling. Other variables that affected the outcomes were the probability of urinary retention after RMUS, and the utility score for urinary continence. Conclusion(s): Based on our economic model and cost data, retropubic midurethral sling is cost-effective compared to autologous rectus fascial sling from the hospital and healthcare perspectives. However, if the cost of retropubic midurethral sling were to increase or the success rate of autologous rectus fascial sling were to improve, autologous rectus fascial sling may become more cost-effective.

jia, z., et al. (2022). "Herbal medicine for infertile women with advanced maternal age undergoing IVF-ET&#xff1a;A Systematic Review and Meta-Analysis."
	
Jiajia, L. and G. Mingxia (2023). "The Efficacy of Intra-Ovarian Infusion of Autologous Platelet-Rich Plasma in Patients With Poor Ovarian Response: A systematic review and meta-analysis."
	
Jiaming, C., et al. (2022). "Clinical evaluation of autologous and allogeneic stem cell therapy for intrauterine adhesions: a systematic review and network meta-analysis."
	
Jian, X., et al. (2023). "Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial neoplasms: a systematic review and meta-analysis."
	
Jianeng, Z., et al. (2021). "Cleavage and blastocyst embryo sequential transfer and IVF outcome: A systematic review."
	
Jiang, C. and F. Zhang (2021). "Clinical effect of pelvic floor electrophysiological treatment on endometrium repair after artificial abortion in early pregnancy and its influence on pregnancy rate." 中国社区医师 37(29): 34‐35.
	Objective: To analyze the clinical effect of pelvic floor electrophysiology therapy in endometrial repair after induced abortion in early pregnancy and its influence on pregnancy rate. Methods: A total of 80 early‐pregnancy women who underwent artificial abortion from September 2017 to September 2018 were selected and randomly divided into two groups, 40 cases in each group. The control group received routine nursing and treatment after induced abortion; the observation group received pelvic floor electrophysiological therapy after induced abortion. The clinical effects of the two groups were compared. Results: The endometrial thickness of the observation group was higher than that of the control group, the incidence of intrauterine adhesion was lower than that of the control group, and the difference was statistically significant (P<0.05). The EMG values of class Ⅱ muscle fibers were significantly higher than those of the control group, and the difference was statistically significant (P<0.05). Conclusion: The application of pelvic floor electrophysiological therapy to women undergoing artificial abortion after early pregnancy can promote endometrial repair, reduce the incidence of intrauterine adhesions, promote the recovery of pelvic floor muscle strength and myoelectric function, and improve the second pregnancy rate.

Jiang, F., et al. (2021). "The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta-analysis." Taiwanese Journal of Obstetrics & Gynecology 60(1): 1-8.
	To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.; Competing Interests: Conflict of interest The authors report no conflict of interest. (Copyright © 2021. Published by Elsevier B.V.)

Jiang, L., et al. (2023). "Pregnancy Outcomes after Uterus-sparing Operative Treatment for Adenomyosis: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 30(7): 543-554.
	Objective: A meta-analysis was conducted to evaluate the overall pregnancy outcomes after uterus-sparing operative treatment in patients with adenomyosis (AD). Data sources: We searched PubMed, Web of Science, Cochrane Library, and Embase for literature from January 2000 to January 2022. Methods of Study Selection: We included all studies reporting reproductive outcomes of uterine-sparing surgery for patients with AD with fertility requirements. Surgical treatment was classified as complete excision or incomplete removal of AD and nonexcisional techniques for induction of necrosis in AD. The latter included physically removing the tissue where pathology is present or disrupting the blood flow to the affected area, involving high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, and uterine artery embolization. Two independent researchers performed study selection according to the screening criteria. Tabulation, Integration, and Results: A total of 13 studies with 1319 patients with AD were included in this study, comprising 795 women wishing fertility. Pooled estimates of pregnancy, miscarriage, and live-birth rates after excisional treatment for women attempting to conceive were 40% (95% confidence interval [CI], 29-52), 21% (95% CI, 16-27), and 70% (95% CI, 64-76), respectively, and corresponding rates after nonexcisional treatment were 51% (95% CI, 42-60), 22% (95% CI, 13-34), and 71% (95% CI, 57-83), respectively. The differences were not statistically significant. Conclusion(s): Excisional treatment could be a treatment consideration for patients with symptomatic AD and infertility for several years or repeated failure of assisted reproductive technology. Nonexcisional techniques may be considered probably for AD-related infertility.Copyright © 2023 AAGL

Jiang, L., et al. (2022). "Different approaches compared the curative effect of laparoscopic resection of para-aortic lymph nodes in gynecological malignant tumors: A systematic review and meta-analysis." Asian journal of surgery.
	
Jiang, L., et al. (2021). "Incidence and Risk of Hypertension in Cancer Patients Treated With Atezolizumab and Bevacizumab: A Systematic Review and Meta-Analysis." Frontiers in Oncology 11: 726008.
	Purpose: This study aims to inform previous clinical assessments to better understand the total risk of hypertension with atezolizumab and bevacizumab (hereafter referred to as "A-B") in cancer patients, and reduce future incidence of hypertension-related cardiovascular complications.; Methods: Databases, including PubMed, Embase, Cochrane, and Web of Science were searched to identify relevant studies, which were retrieved from inception to March 6, 2021. Studies focused on cancer patients treated with A-B that provided data on hypertension were included. Statistical analyses were conducted to calculate hypertension incidence and relative risk (RR) with a random-effects or fixed-effects model, hinging on heterogeneity status.; Results: Ten studies including 2106 patients with renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), ovarian cancer, anal cancer, neuroendocrine tumors (NETs), and cervical cancer were selected for this meta-analysis. For patients treated with A-B, the all-grade and high-grade (grade 3) hypertension incidence were 31.1% (95% CI: 25.5-37.3) and 14.1% (95% CI: 10.9-18.1), respectively. No significant difference was observed in all-grade hypertension incidence between RCC and a non-RCC patients (32.9% [95% CI: 25.3-42.6] v.s. 29.2% [95% CI: 19.7-39.6)]). However, the number of high-grade hypertension incidence in RCC patients (9.4% [95% CI: 4.1-21.3]) was lower than that of non-RCC patients (15.6% [95% CI: 12.8-19.1]). RCC or HCC patients who received the A-B treatment were associated with significantly increased risk of all-grade hypertension with a RR of 7.22 (95% CI: 3.3-15.7; p = 0.6) compared with patients treated with atezolizumab.; Conclusions: Cancer Patients treated with atezolizumab and bevacizumab have a significantly increased risk of hypertension. Sufficient monitoring is highly recommended to prevent the consequences of treatment-induced hypertension and other cardiovascular complications.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Jiang, Tan, Li and Li.)

Jiang, M., et al. (2022). "Clinical efficacy of laparoscopic surgery combined with drug therapy for endometriosis: A meta-analysis." Medical engineering & physics 107: 103866.
	Objective: To systematically investigate the clinical efficacy and prognosis of laparoscopic surgery combined with drug therapy for endometriosis.; Methods: Clinical randomized controlled trials regarding laparoscopic surgery combined with drug therapy for endometriosis and published between 2010 and 2022 were retrieved from PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and Wanfang databases. Meta-analysis and sensitivity tests were performed using the Stata16.0 software.; Results: A total of 1332 articles were retrieved. Of them, 11 studies were included for final analysis, comprising of 521 cases in the treatment group (laparoscopic surgery combined with drug therapy) and 530 cases in the control group (laparoscopic surgery alone). Meta-analysis results showed that compared with the control group, the combined treatment had higher treatment effective rate [OR = 4.542, 95% CI (3.062, 6.736), P < 0.001], pregnancy rate [OR = 3.341, 95% CI (2.336, 4.780), P < 0.001], and lower incidence of adverse reactions [OR = 0.348, 95% CI (0.208, 0.583), P < 0.001] and recurrence rate [OR = 0.187, 95% CI (0.106, 0.328), P < 0.001]. In addition, after treatment, estradiol [SMD = -3.417, 95% CI (-4.631, -2.203), P < 0.001] and follicle-stimulating hormone [SMD = -1.976, 95% CI (-3.202, -0.751), P = 0.002] in the treatment group were significantly lower than the control group.; Conclusion: Compared with laparoscopic surgery alone, laparoscopic surgery combined with drug therapy demonstrated better clinical efficacy and improved postoperative infertility and recurrence rate for treating endometriosis.; Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper. (Copyright © 2022. Published by Elsevier Ltd.)

Jiang, M., et al. (2019). "Traditional Chinese herb for low endometrial receptivity and its effect on pregnancy: Protocol for a systematic review and meta-analysis." Medicine 98(47): e17841.
	Background: Low endometrial receptivity is associated with infertility in women through multiple and complex mechanisms. Existing treatments are not always effective. Symptomatic drugs such as estradiol valerate and/or aspirin do not completely solve the problem. Traditional Chinese herbs have been widely used in infertility and uterine disease including low endometrial receptivity. However, their effectiveness and safety are still obscure and deserve further investigation.; Objective: To assess the effect and safety of traditional Chinese herbs in treating low endometrial receptivity.; Methods: We will summarize and meta-analyze randomized controlled trials (RCTs) of traditional Chinese herbs for the treatment of low endometrial receptivity. RCTs comparing traditional Chinese herbs with blank control, placebo, or conventional therapies will be included. RCTs comparing traditional Chinese herbs plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WANFANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. GRADE pro GDT web solution will be used for evidence evaluation.; Results: This review will evaluate the effects of traditional Chinese herbs on estradiol, progesterone, thickness, volume, and perfusion index(PI) of the endometrium, pregnancy rate, and symptoms.; Conclusions: This review will provide clear evidence to assess the effectiveness and safety of traditional Chinese herbs for low endometrial receptivity.; Osf Registration Number: DOI 10.17605/OSF.IO/M85VT.

Jiang, N., et al. (2022). "Diagnosis and Nursing Intervention of Gynecological Ovarian Endometriosis with Magnetic Resonance Imaging under Artificial Intelligence Algorithm." Computational intelligence and neuroscience 2022: 3123310.
	This research was aimed to study the application value of the magnetic resonance imaging (MRI) diagnosis under artificial intelligence algorithms and the effect of nursing intervention on patients with gynecological ovarian endometriosis. 116 patients with ovarian endometriosis were randomly divided into a control group (routine nursing) and an experimental group (comprehensive nursing), with 58 cases in each group. The artificial intelligence fuzzy C-means (FCM) clustering algorithm was proposed and used in the MRI diagnosis of ovarian endometriosis. The application value of the FCM algorithm was evaluated through the accuracy, Dice, sensitivity, and specificity of the imaging diagnosis, and the nursing satisfaction and the incidence of adverse reactions were used to evaluate the effect of nursing intervention. The results showed that, compared with the traditional hard C-means (HCM) algorithm, the artificial intelligence FCM algorithm gave a significantly higher partition coefficient, and its partition entropy and running time were significantly reduced, with significant differences ( P < 0.05). The average values of Dice, sensitivity, and specificity of patients' MRI images were 0.77, 0.73, and 0.72, respectively, which were processed by the traditional HCM algorithm, while those values obtained by the improved artificial intelligence FCM algorithm were 0.92, 0.90, and 0.93, respectively; all the values were significantly improved ( P < 0.05). In addition, the accuracy of MRI diagnosis based on the artificial intelligence FCM algorithm was 94.32 ± 3.05%, which was significantly higher than the 81.39 ± 3.11% under the HCM algorithm ( P < 0.05). The overall nursing satisfaction of the experimental group was 96.5%, which was significantly better than the 87.9% of the control group ( P < 0.05). The incidence of postoperative adverse reactions in the experimental group (7.9%) was markedly lower than that in the control group (24.1%), with a significant difference ( P < 0.05). In short, MRI images under the artificial intelligence FCM algorithm could greatly improve the clinical diagnosis of ovarian endometriosis, and the comprehensive nursing intervention would also improve the prognosis and recovery of patients.; Competing Interests: The authors declare no conflicts of interest. (Copyright © 2022 Nijie Jiang et al.)

Jiang, Q., et al. (2021). "Lentinan Combined with (125)I Brachytherapy for Recurrent Ovarian Cancer." Evidence-based complementary and alternative medicine : eCAM 2021: 2472444.
	OBJECTIVE: To investigate the clinical value of lentinan combined with (125)I brachytherapy in the treatment of recurrent ovarian cancer. METHODS: A total of 160 patients with recurrent ovarian cancer admitted at Jiaozhou Central Hospital from June 2009 to October 2015 were enrolled in this study and randomly divided into observation group (80 cases) and control group (80 cases). The control group received chemotherapy. Observation group (80 cases) was treated with lentinan combined with (125)I brachytherapy on the basis of control group, and the efficacy, adverse reactions, and Karnofsky Performance Scale (KPS) and quality of life scale (QOL) scores of the two groups were analyzed and compared. RESULTS: After treatment, the levels of CA125, CA199, and CA724 in the 2 groups were markedly lower than those before treatment, and the observation group was lower than the control group (P < 0.05). After treatment, the proportion of CD4+/CD8+ cells and helper T cells and NK cells in the control group remarkably depleted, while the proportion of CD4+/CD8+ cells, NK cells, and B cells in the observation group increased significantly compared to that before treatment, and the level of IgA, IgG, and IgM in the control group decreased, while that in the observation group showed no conspicuous difference compared with that before chemotherapy (P > 0.05). The effective rate of observation group (85%) was higher than that of control group (75%) (P < 0.05). The overall survival of patients in the control group was (16.2 ± 2.04) months and that of the observation group was (24.8 ± 1.8) months. KPS and QOL scores in both groups were enormously higher than those before treatment, and the observation group was higher than the control group (P < 0.05). The incidence of hemoglobin reduction, leukopenia, aglobulia, granulocytopenia, nausea and vomiting, hepatorenal toxicity, and neurovirulence in the observation group was significantly lower than that in the control group. CONCLUSION: Lentinan combined with (125)I brachytherapy is effective in treating recurrent ovarian cancer, with mild adverse reactions and good tolerance.

Jiang, S., et al. (2022). "The Effects of Letrozole and Metformin Combined with Targeted Nursing Care on Ovarian Function, LH, and FSH in Infertile Patients with Polycystic Ovary Syndrome." Journal of healthcare engineering 2022: 3712166.
	Background: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder in women of gestational age and the most common cause of female infertility. This study aimed to investigate the effect of letrozole and metformin combined with targeted nursing on ovarian function, LH, and FSH in infertile patients with PCOS.; Methods: A total of 72 infertile patients with PCOS were divided into the control group and combined group. The control group was given metformin tablets combined with targeted nursing therapy. The combined group was treated with letrozole on the basis of the control group. Ovarian function, LH, and FSH were compared between the two groups before and after treatment.; Results: After treatment, the total effective rate (94.44%) of the combined group was significantly higher than that of the control group (80.56%). After treatment, the levels of HbA1c, FINS, HOMA-IR, TG, and TC in the two groups were lower than those before treatment, and the HDL-C level was higher than that before treatment. The full-term delivery rate, ovulation rate, and normal menstrual rate in the combined group were higher than those in the control group. After treatment, the LH level in the combined group was lower than that in the control group, and the FSH level was higher than that in the control group. After 1 month, 3 months, and 5 months of treatment, RI, PI, and ovarian volume were decreased, and the endometrial thickness was increased in both groups. Also, after 5 months of treatment, the RI, PI, and ovarian volume in the combined group were significantly lower than those in the control group, and the endometrial thickness was significantly higher than that in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups.; Conclusion: The combination of letrozole and metformin with targeted nursing in the treatment of infertility patients with PCOS has better clinical effect and high safety. It can improve endometrial receptivity and ovarian reserve function and regulate LH and FSH levels.; Competing Interests: The authors declare that they have no competing interests. (Copyright © 2022 Shuai Jiang et al.)

Jiang, T. and X. Xue (2023). "Baseball Suture versus Traditional Suture in Laparoscopic Myomectomy: A Systematic Review and Meta-Analysis." Clinical and Experimental Obstetrics and Gynecology 50(11): ceog5011251.
	Background: Uterine myoma, which seriously threatens women's physical and mental health and quality of life, is the most common benign pelvic tumor in gynecology. At present, laparoscopic myomectomy (LM) has become an effective and commonly surgical method in clinical practice. The aim of this study, using meta-analysis method, is to analyze the advantages and disadvantages of baseball suture comparing with traditional one, and provide a theoretical basis for the selection of surgical suture methods. Method(s): CNKI, WanFang Data, VIP, PubMed, web of science and the Cochrane Library are searched to collect original data and cases. Two researchers independently screen the literature according to the inclusion and exclusion criteria, extract the data and cross check them. Then RevMan 5.4 and STATA 14 are used for statistical analysis. The difference is statistically significant (p < 0.05). Result(s): Compared with the traditional suture method, the operation time of LM with baseball suture method is shorter, the amount of intraoperative bleeding is less, the time required for postoperative exhaust, first getting out of bed, hospitalization, and uterine incision suture is shorter, the incidence of needle eye bleeding is lower, the decline of average hemoglobin is lower, and the incidence of pelvic infection is lower, while the difference is statistically significant (p < 0.05). The incidence of postoperative morbidity is lower, while the difference is not statistically significant (p > 0.05). Conclusion(s): Baseball suture has progressiveness and important value in LM surgical suture. The hemostasis and healing effect is ideal, which can enable patients to recover more quickly, reduce the pain and economic burden caused by the operation, and also enable surgeons to complete the operation more conveniently and efficiently. The protocol of the review was registered on the PROSPERO platform (https://www.crd.york.ac.uk/PROSPERO/) with the registration number CRD42022370262.Copyright © 2023 The Author(s).

Jiang, T.-Y., et al. (2021). "A comparative study of the efficiency and safety of chemotherapy as a therapeutic method for recurrent or resistant gestational trophoblastic neoplasia: A protocol for systematic review and meta-analysis." Medicine 100(24): e26263.
	Background: Gestational trophoblastic neoplasia (GTN) is an infrequent spectrum of placental malignant cases. Generally, single-agent or multiple-agent chemotherapy is used to treat the condition. The condition has a significant impact on women in the childbearing age, which makes post-chemo fertility and obstetrical results a significant contemplation. Nearly 25% of GTN tumors are recurrent, or have a likelihood of relapsing after, the first round of chemotherapy. Therefore, these resistive and recurring lesions require salvage chemotherapy with or without surgical treatment. Therefore, the current meta-analysis and systematic review will assess the effectiveness and level of safety when using chemotherapy to treat women with resistive or recurring GTN.; Methods: The current study will perform a comprehensive systematic search for randomized controlled trials (RCTs) that have assessed the efficacy and safeness of chemo as a line of treatment for women with resistive or recurring GTN. To this end, a search will be conducted on the following electronic databases: Web of Science, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), EMBASE, WanFang database, and the Cochrane Library. The search will cover the period from the inception of databases to May 2021. In order to identify additional related studies, we will manually search the reference lists of suitable research articles and related systematic reviews. A pair of independent authors will review the titles/abstracts of the studies to check if the studies are eligible, which is proceeded by screening the full texts. This study will employ a uniform data extraction table for data extraction. Moreover, based on the Cochrane Risk of Bias Tool, this protocol review also assesses the bias risk in the studies involved.; Results: A comprehensive synthesis of existing indication on chemo treatment for women with resistive or recurring GTN.; Conclusion: The results offer fresh references for evaluating the effectiveness and safeness of chemo-based treatment for women with resistive or recurring GTN.; Ethics and Dissemination: An ethical approval is not needed as all data are published.; Review Registration Number: May 17, 2021.osf.io/uwky7. (https://osf.io/uwky7/).; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Jiang, Y., et al. (2022). "Morphine in Combination with Ketamine Improves Cervical Cancer Pain and Suppresses Immune Function via the JAK3/STAT5 Pathway." Pain research & management 2022: 9364365.
	Background: The role of ketamine as an adjuvant for morphine in the treatment of cancer pain and immune functions has been confirmed. This study aimed to explore the role of morphine and ketamine on cancer pain and T cells of patients with cervical cancer (CC).; Methods: T cells were isolated from peripheral blood mononuclear cells (PBMC) of CC patients by positive selection using anti-CD3 beads. The isolated T cells were assigned into three groups: the control group, the morphine group, and the morphine + ketamine (Mor + Ket) group. The percentages of CD4 + and CD8 + were analyzed by flow cytometry. The levels of interferon (IFN)- γ , interleukin (IL)-2, and IL-17 and the corresponding mRNA expression in vitro were determined using ELISA and qRT-PCR, respectively. Western blotting was used for detection of JAK3/STAT5 pathway-related proteins after naltrexone treatment in vitro. Afterwards, all the patients were further divided into the morphine group and the Mor + Ket group in accordance with the principles of the randomized and double-blind method to assess pain intensity.; Results: Our in vivo results showed that drug combinations relieved cancer pain more effectively than morphine intervention. The in vitro results demonstrated that the combination of morphine and ketamine may decrease CD4 + percentage, CD4 + /CD8 + ratio, and the levels of IFN- γ , IL-2, and IL-17 via the JAK3/STAT5 pathway.; Conclusions: Our finding indicated that morphine-ketamine combination could improve cancer pain and repress immune function via the JAK3/STAT5 pathway in the progression of CC.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Yurong Jiang et al.)

Jiang, Y., et al. (2023). "Reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with a septate uterus: a systematic review and meta-analysis." American Journal of Obstetrics & Gynecology MFM 5(1): 100762.
	Objective: The aim of this systematic review and meta-analysis was to analyze the reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility.; Data Sources: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, and Chinese Biomedical Literature Database (CBM) databases were electronically searched. The search time frame was from inception up to July 2021. The English search terms were (arcuate* and uter*), (sept* and uter*), (subseptate* and uter*), metroplast*, septoplast*, and resect*.; Study Eligibility Criteria: Selection criteria included randomized controlled trials, cohort studies, and case series that explored reproductive outcomes after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility with or without a control group.; Methods: The primary outcomes were the live birth rate and eventual postoperative live birth rate after hysteroscopic septum resection. The secondary outcomes were the clinical pregnancy rate, preterm birth rate, and miscarriage rate. Study-level proportions of outcomes were transformed using the Freeman-Tukey double-arcsine transformation to calculate pooled values for the postoperative rates; the counted data were analyzed using relative risk as the effect analysis statistic, and each effect size was provided with its 95% confidence interval. Heterogeneity between the results of the included studies was analyzed using the I 2 test.; Results: Overall, 5 cohort studies and 22 case series involving 1506 patients were included. In patients with a septate uterus and recurrent miscarriage, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 1.77; 95% confidence interval, 1.26-2.49; P=.001; I 2 =0%), resulting in a postoperative live birth rate of 66% (95% confidence interval, 59-72), and septum resection was associated with a reduced preterm birth rate (relative risk, 0.15; 95% confidence interval, 0.04-0.53; P=.003; I 2 =0%) and miscarriage rate (relative risk, 0.36; 95% confidence interval, 0.20-0.66; P=.0009; I 2 =0%). In patients with a septate uterus and primary infertility, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 4.12; 95% confidence interval, 1.19-14.29; P=.03; I 2 =0%) and clinical pregnancy rate (relative risk, 2.28; 95% confidence interval, 1.04-4.98; P=.04; I 2 =0%). The postoperative live birth rate was 37% (95% confidence interval, 30-44), and the miscarriage rate of patients with primary infertility was reduced (relative risk, 0.19; 95% confidence interval, 0.06-0.56; P=.003). The efficacy of hysteroscopic septum resection in patients with secondary infertility was unclear. However, their postoperative live birth rate was found to be 41% (95% confidence interval, 2-88).; Conclusion: Hysteroscopic septum resection is associated with an increased live birth rate and a reduced miscarriage rate in patients with recurrent miscarriage or primary infertility, indicating that septum resection may improve the reproductive outcomes of these patients. The effectiveness of septum resection was unclear for patients with secondary infertility. These findings are limited by the quality of the included studies, warranting further randomized controlled trials, including only patients with recurrent miscarriage or primary infertility. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Jiang, Z., et al. (2021). "Effects of PICCO in the guidance of goal-directed fluid therapy for gastrointestinal function after cytoreductive surgery for ovarian cancer." American journal of translational research 13(5): 4852-4859.
	OBJECTIVE: To explore the effects of PICCO on the Guidance of Goal-Directed Fluid Therapy for gastrointestinal function after cytoreductive surgery for ovarian cancer. METHODS: A total of 98 patients who received cytoreductive surgery for ovarian cancer under general anesthesia in our hospital were stochastically divided into the observation group and control group, with 49 cases in each group. The observation group received PICCO guided goal-directed fluid therapy, while patients in the control group were treated with conventional fluid therapy. At last, the total amount of infusion, the time required for postoperative gastrointestinal function recovery and related recovery rating, the first time to get out of bed after the surgery and the total hospitalization time were observed and compared between the two groups. RESULTS: The observation group had less time for gastrointestinal function recovery and had better functional recovery rating as well as other indicators than the control group. Besides, the observation group had less volume of infusion, needed shorter time to get out of bed and had a shorter length of hospital stay than the control group (all P<0.05). CONCLUSION: PICCO guided goal-directed liquid therapy can effectively improve the recovery of gastrointestinal function and reduce the length of stay in patients with ovarian cancer after cytoreductive surgery.

Jiang, Z. and H. Shen (2022). "Mitochondria: emerging therapeutic strategies for oocyte rescue." Reproductive sciences (Thousand Oaks, Calif.) 29(3): 711-722.
	As the vital organelles for cell energy metabolism, mitochondria are essential for oocyte maturation, fertilization, and embryo development. Abnormalities in quantity, quality, and function of mitochondria are closely related to poor fertility and disorders, such as decreased ovarian reserve (DOR), premature ovarian aging (POA), and ovarian aging, as well as maternal mitochondrial genetic disease caused by mitochondrial DNA (mtDNA) mutations or deletions. Mitochondria have begun to become a therapeutic target for infertility caused by factors such as poor oocyte quality, oocyte aging, and maternal mitochondrial genetic diseases. Mitochondrial replacement therapy (MRT) has attempted to use heterologous or autologous mitochondria to rebuild healthy state of oocyte by increasing the amount of mitochondria (e.g., partial ooplasm transfer, autologous mitochondrial transfer), or to stop the transmission of mtDNA diseases by replacing abnormal maternal mitochondria (e.g., pronuclei transfer, spindle transfer, polar body transfer). Among them, autologous mitochondrial transfer is the most promising therapeutic technology as of today which does not involve using a third party, but its clinical efficacy is controversial due to many factors such as the aging phenomenon of germ line cells, the authenticity of the existence of ovarian stem cells (OSC), and secondary damage caused by invasive surgery to patients with poor ovarian function. Therefore, the research of optimal autologous cell type that can be applied in autologous mitochondrial transfer is an area worthy of further exploration. Besides, the quality of germ cells can also be probably improved by the use of compounds that enhance mitochondrial activity (e.g., coenzyme Q10, resveratrol, melatonin), or by innovative gene editing technologies which have shown capability in reducing the risk of mtDNA diseases (e.g., CRISPR/Cas9, TALENTs). Though the current evidences from animal and clinical trials are not sufficient, and some solutions of technical problems are still needed, we believe this review will guide a new direction in the possible clinical applied mitochondrial-related therapeutic strategies in reproductive medicine. (© 2021. Society for Reproductive Investigation.)

Jiapeng, H., et al. (2022). "Comparative efficacy of electrical stimulation therapies for overactive bladder in adults during the COVID-19 pandemic: a network meta-analysis of randomized controlled trials."
	
Jiaqi, Z., et al. (2021). "Administration of inositols or metformin to women with polycystic ovary syndrome: a network meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Jiaqi, Z., et al. (2021). "Novel nutrition agents for improving the endocrine and metabolic profiles in women with PCOS: A network meta-analysis."
	
Jidong, D. E., et al. (2023). "Culturally adapted psychological intervention for treating maternal depression in British mothers of African and Caribbean origin: a randomized controlled feasibility trial." Clinical Psychology & Psychotherapy 30(3): 548‐565.
	BACKGROUND: Women are likely to suffer from maternal depression due to childbirth difficulties and parenting responsibilities, leading to long‐term negative consequences on their children and families. British mothers of African/Caribbean origin uptake of mental healthcare is low due to the lack of access to culturally appropriate care. METHODS: A mixed‐methods randomized controlled feasibility trial was adopted to test the appropriateness and acceptability of Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) for treating maternal depression compared with Psychoeducation (PE). Mothers (N = 26) aged 20‐55 were screened for depression using the Patient Health Questionnaire (PHQ‐9). Those who scored >5 on PHQ‐9 were further interviewed using the Revised Clinical Interview Schedule to confirm the diagnosis and randomized into LTP+CaCBT (n = 13) or PE (n = 13) groups. Assessments were taken at baseline, end of the intervention at 3‐ and 6‐months post‐randomization. N = 2 focus groups (LTP+CaCBT, n = 12; PE, n = 7) and N = 8 individual interviews were conducted (LTP+CaCBT, n = 4; PE, n = 4). RESULTS: The LTP+CaCBT group showed higher acceptability, feasibility and satisfaction levels than the PE group. Participants experienced the intervention as beneficial to their parenting skills with reduced depression and anxiety in the LTP+CaCBT compared to the PE group. CONCLUSIONS: This is the first feasibility trial of an integrated online parenting intervention for British African and Caribbean mothers. The results indicated that culturally adapted LTP+CaCBT is acceptable and feasible. There is a need to study the clinical and cost‐effectiveness of LTP+CaCBT in an appropriately powered randomized control trial and include the child's outcomes. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (no. NCT04820920).

Jie, P., et al. (2021). "Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fuke Qianjin Tablet." Evidence-based complementary and alternative medicine : eCAM 2021: 8861631.
	Purpose: The aim of the research was to evaluate the efficacy and safety associated with Fuke Qianjin tablet combined with conventional therapy in the treatment of pelvic inflammatory diseases and associated complications (endometritis) using a meta-analysis approach. Patients and Methods . We searched 8 electronic databases up to December 31, 2019, including PubMed, the Cochrane Library, Embase, Web of Science, CNKI, WanFang, VIP, and SinoMed. Eligible studies were clinical trials of Fuke Qianjin tablet combined with conventional therapy used in the treatment of acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and endometritis. The meta-analysis was performed using STATA15 software.; Results: A total of 125 RCTs ( n = 14,494) were shortlisted for the meta-analysis, which included 23 trials for acute pelvic inflammatory disease, 69 trials for chronic pelvic inflammatory disease, and 33 trials for endometritis. The overall analysis illustrated Fuke Qianjin tablet combined with conventional therapy was significantly more efficacious than conventional therapy alone across all types of antibiotics treatment for acute pelvic inflammatory disease (OR = 5.57, 95% CI 4.09-7.58, Z = 10.90, p =0.001), chronic pelvic inflammatory disease (OR = 4.70, 95% CI 4.07-5.42, Z = 21.21, p =0.001) and endometritis (OR = 5.09, 95% CI 4.03-6.43; Z = 13.63, p =0.001) in both primary endpoints and secondary endpoints. There is also a trend that Fuke Qianjin tablet combined with conventional therapy has lower adverse reaction rates than conventional therapy alone.; Conclusion: Fuke Qianjin tablet combined with conventional therapy showed better clinical efficacy in the treatment of acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and endometritis. There were no obvious drug-related adverse reactions. Fuke Qianjin tablet presented advantages in shortening the remission time of clinical symptoms, reducing the concentration of serum inflammatory factors, improving endometrial thickness, menstruation, and reducing relapse rate.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2021 Pan Jie et al.)

Jie, Z., et al. (2022). "Efficacy of Dehydroepiandrosterone Priming in Women with Poor Ovarian Response Undergoing IVF/ICSI: A Meta-regression Study and Systematic Review."
	
Jin, B., et al. (2022). "The Efficacy and Safety of Dingkun Pill in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Evidence-based complementary and alternative medicine : eCAM 2022: 8698755.
	Objective: Dingkun Pill (DKP) is a proprietary Chinese medicine that has been utilized for patients with gynecological diseases, and its clinical application has been widely accepted in China. However, the effects of DKP on reproduction and metabolism in women with polycystic ovary syndrome (PCOS) have never been systematically evaluated. Our objective was to evaluate the efficacy and safety of DKP in treating reproductive and metabolic abnormalities with PCOS.; Methods: We searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database up until January 2022 to identify randomized controlled trials (RCTs). The methodological quality of the included RCTs was estimated using the Cochrane collaboration risk-of-bias instrument, and the meta-analysis was performed using RevMan.; Results: A total of 22 RCTs (including 1994 participants) were identified. DKP, combined with ovulation-inducing drugs (OID) or combined oral contraceptives (COC) was superior to OID or COC alone in improving the pregnancy rate (relative risk (RR) 1.84, 95% CI 1.62 to 2.11 and RR 1.38, 95% CI 1.16 to 1.64, respectively), ovulation rate (RR 1.38, 95% CI 1.03 to 1.84 and RR 1.23, 95% CI 1.11 to 1.37, respectively), endometrial thickness (weighted mean difference (WMD) 2.50, 95% CI 1.91 to 3.09 and WMD 0.62, 95% CI 0.08 to 1.16, respectively), luteinizing hormone (WMD -1.93, 95% CI -2.80 to-.07 and WMD -1.79, 95% CI -2.66 to-0.92, respectively), and testosterone (standardized mean difference (SMD) -2.12, 95% CI -3.01 to-1.24 and SMD -1.21, 95% CI -1.64 to-0.78, respectively). DKP combined with COC led to a greater improvement in homeostasis model assessment- β (WMD 20.42, 95% CI 16.85 to 23.98) when compared with COC alone. There was a significant difference between DKP and COC in terms of decreasing total cholesterol (WMD -0.37, 95% CI -0.72 to-0.02), triacylglycerol (WMD -0.85, 95% CI -1.50 to-0.20), and free fatty acid (WMD -130.00, 95% CI -217.56 to-42.22). However, DKP did not affect the follicle stimulating hormone, fasting blood glucose, fasting insulin, body mass index, waist-to-hip ratio, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Adverse reactions were more common in COC alone compared to DKP and COC in combination (RR 0.22, 95% CI 0.07 to 0.63).; Conclusion: DKP shows promise in modifying reproductive and metabolic parameters in patients with PCOS and may be used as a primary choice in conventional or complementary therapies for PCOS. The quality of the evidence analyzed was suboptimal, and therefore, our results should be interpreted cautiously. More prospective large-scale and well-designed RCTs, as well as longer intervention durations are required in the future to draw more reliable conclusions.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Bao Jin et al.)

Jin, H. (2021). "Clinical observation of hysteroscopic surgery combined with mifepristone in the treatment of missed abortion." 临床研究 Clinical Research 29(8): 89‐90.
	Objective: To analyze the efficacy of hysteroscopic surgery combined with mifepristone in the treatment of missed abortion. Methods: A total of 82 patients with missed abortion who were admitted to Anyang People's Hospital from February 2018 to January 2020 were selected and divided into an observation group and a control group according to the random number table method, with 41 cases in each. The control group was treated with uterine evacuation, and the observation group was treated with hysteroscopic surgery combined with mifepristone. The clinical indicators, abortion results and residual uterine cavity were compared between the two groups. RESULTS: Compared with the control group, the observation group had shorter operation time, postoperative vaginal bleeding time and hospital stay, lower intraoperative blood loss, higher complete abortion rate, lower uterine residual rate, and the differences were significant (P < 0.05). 0.05). Conclusion: Hysteroscopic surgery combined with mifepristone therapy for missed abortion patients can effectively improve the efficiency of abortion, reduce intraoperative bleeding and postoperative vaginal bleeding, shorten the recovery time, and facilitate the recovery of patients.

Jin, J. (2022). "Treatment of Menopause Symptoms With Hormone Therapy." JAMA 327(17): 1716.
	
Jin, J., et al. (2023). "Combination of HIFU with sulfur hexafluoride microbubbles in the treatment of solitary uterine fibroids: a systematic review and meta-analysis." European radiology.
	Objectives: To assess the efficacy and safety of sulfur hexafluoride microbubbles on ultrasound-guided high-intensity focused ultrasound (HIFU) ablation of uterine fibroids.; Methods: Studies that compared HIFU-microbubble combination with HIFU-only in patients with uterine fibroids were searched from inception to April 2022. The standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for different outcome parameters was calculated.; Results: Seven studies were included, with a total of 901 patients (519 in the combination group and 382 in the HIFU-only group). The energy consumption for treating 1 cm 3 of the lesion in the combination group was less than that in the HIFU-only group [SMD = - 2.19, 95%CI (- 3.81, - 0.57), p = 0.008]. The use of microbubbles was associated with shortening the duration of the treatment and sonication [SMD = - 2.60, 95%CI (- 4.09, - 1.10), p = 0.0007; SMD = - 2.11, 95%CI (- 3.30, - 0.92), p = 0.0005]. The rates of significant greyscale changes during HIFU were greater in the combination group, as well as the increase of non-perfused volume ratio [RR = 1.26, 95%CI (1.04, 1.54), p = 0.02; SMD = 0.32, 95%CI (0.03, 0.61), p = 0.03]. The average sonication durations to reach significant greyscale changes and for ablating 1 cm 3 of the fibroid lesion were shorter in the combination group [SMD = - 1.24, 95%CI (- 2.02, - 0.45), p = 0.002; SMD = - 0.22, 95%CI (- 0.42, - 0.02), p = 0.03]. The two groups had similar post-HIFU adverse effects, while the combination group had fewer intraprocedural adverse events like abdominal pain, sacrum pain, and leg pain.; Conclusions: Sulfur hexafluoride microbubbles can be safely used to enhance and accelerate the ablation effects of HIFU in the treatment of uterine fibroids.; Clinical Relevance Statement: The combination of HIFU with sulfur hexafluoride microbubbles offers a promising non-invasive treatment option for patients with uterine fibroids.; Key Points: • Sulfur hexafluoride microbubbles combined with ultrasound-guided high-intensity focused ultrasound (USgHIFU) has potential advantages in the treatment of uterine fibroids. • Sulfur hexafluoride microbubbles not only enhance the effects of USgHIFU treatment for uterine fibroids but also shorten its duration. • Sulfur hexafluoride microbubbles do not increase the incidence of USgHIFU-related adverse events in the treatment of uterine fibroids. (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Jin, M., et al. (2020). "Palliative treatment for bowel obstruction in ovarian cancer: a meta-analysis." Archives of Gynecology and Obstetrics 302(1): 241-248.
	Objective: To comprehensively evaluate and compare outcomes of surgical versus nonsurgical palliative interventions for bowel obstruction due to ovarian cancer.; Methods: Studies were obtained from database search systems of Pubmed, Medline, Wiley, Springerlink, Kluwer, Web of science and Science direct. Data were analyzed by the meta-analysis method and the random-effect or fixed-effect model. The heterogeneity between the studies was evaluated by I 2 index and the data were analyzed using STATA version 14.1.; Results: 12 studies involving 2778 cases of bowel obstruction in ovarian cancer were included, including 1225 cases of surgery and 1553 cases of palliative nonsurgical treatment. Surgery group had significantly higher remission rate of bowel obstruction (OR = 0.350, 95% CI 0.067-1.819, P = 0.000),but had no manifesting difference in the recurrence rate compared no-surgery group (RR = 0.88, 95% CI 0.76-1.03, P = 0.106). In 30-day mortality rate, surgery group had higher mortality rate (RR = 0.453, 95% CI 0.161-1.272, P = 0.000). But, surgical treatment can markedly prolong survival period (HR = 0.333, 95% CI 0.275-0.390, P = 0.000) compared nonsurgical treatment.; Conclusions: Surgery can significantly relieve the symptom of intestinal obstruction, prolonging the survival period, but had no impact on the recurrence. Compared with no-surgery group, surgery group suffered higher 30-day mortality.

Jin, P., et al. (2022). "High-quality nursing care on psychological disorder in ovarian cancer during perioperative period: A systematic review and meta-analysis." Medicine 101(27): e29849.
	Background: This study aimed to explore the effect of high-quality nursing care (HQNC) on psychological disorder in patients with ovarian cancer (OC) during the perioperative period (PPP).; Methods: A literature search was performed at the Cochrane Library, PUBMED, Excerpt Medica Database, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their inception until March 1, 2022. Two authors independently performed study selection, data collection, and methodological quality evaluation. The outcomes were anxiety (as measured by the Self-rating Anxiety Scale), depression (as measured by Self-rating Depression Scale), length of hospital stay, and rate of patient satisfaction.; Results: Eight trials involving 742 patients with OC were included in this study. Results of the data analysis showed that patients who received HQNC had a more promising effect on anxiety relief (mean difference, -9.00; random 95% confidence interval, -11.36 to -6.63; P < .001) and depression decrease (mean difference, -7.62; random 95% confidence intervals, -8.45 to -6.78; P < .001) than patients who underwent routine nursing care.; Conclusion: This study summarized the latest evidence of HQNC on psychological disorder relief in patients with OC during perioperative period. These findings showed that HQNC may benefit patients with anxiety and depression.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Jin, S. and Y. Je (2021). "Dairy Consumption and Total Cancer and Cancer-Specific Mortality: A Meta-Analysis of Prospective Cohort Studies." Advances in nutrition (Bethesda, Md.).
	The association between dairy consumption and cancer mortality varies among studies and remains unclear. Thus, we conducted a comprehensive meta-analysis of prospective cohort studies to examine the association between dairy consumption and total cancer and cancer-specific mortality. We sought eligible studies in PubMed and Web of Science databases for all publications through March 2021, and pooled relative risks (RR) and 95% confidence intervals were calculated. We identified 34 prospective cohort studies including 3,171,186 participants and 88,545 deaths. Compared with low milk consumption, high milk consumption was associated with higher cancer mortality in females (RR:1.10; 95% CI: 1.01, 1.21) and people consuming high/whole-fat milk (fat content ≥ 3.5%) (RR:1.17; 95% CI: 1.07, 1.28). Increased risks of cancer-specific mortality were detected for liver (RR:1.13; 95% CI: 1.02, 1.26), ovarian (RR:1.32; 95% CI: 1.13, 1.55), and prostate (RR:1.23; 95% CI: 1.02, 1.48) cancers. Also, females with high consumption of fermented milk had a lower cancer mortality risk (RR:0.85; 95% CI: 0.77, 0.94). High cheese consumption was not associated with total cancer mortality, rather with higher colorectal cancer mortality (RR:1.22; 95% CI: 1.02, 1.46). There was no association between butter (RR:1.06; 95% CI: 0.70, 1.59) or total dairy product consumption (RR:0.99; 95% CI: 0.95, 1.03) and cancer mortality. Our results imply that high milk consumption, especially high/whole-fat milk, was associated with higher cancer mortality, while fermented milk consumption was associated with lower cancer mortality, and this was particularly evident in females. Consequently, further studies are warranted.

Jin, X., et al. (2021). "Efficacy of hysteroscopic cold knife separation on intrauterine adhesions." American journal of translational research 13(7): 8351-8357.
	OBJECTIVE: This research aimed to explore the efficacy of hysteroscopic cold knife separation in the treatment of intrauterine adhesions (IUA). METHODS: Altogether 110 patients with IUA who were treated in our hospital were randomized into the observation group (n=55, hysteroscopic cold knife) and the control group (n=55, hysteroscopic electroacupuncture and collecting ring). This research compared the operation-related indexes (operation time, intraoperative blood loss, amount of distending media), IUA and menstrual flow, endometrial epithelization of the uterine wound, endometrial thickness one month after operation, recurrence and pregnancy rates one year after operation. RESULTS: The operation time and intraoperative blood loss in the observation group were less than those in the control group (all P<0.05). After treatment, the total effective rate of IUA, menstrual flow and satisfaction rate of endometrial epithelization of the uterine wound in the observation group were higher than those in the control group, and the recurrence rate of the former one year after operation was lower (all P<0.05). One month after operation, the thickness of the endometrium in the observation group was clearly larger than that in the control group on the 11th and 13th day of menstruation (all P<0.05). CONCLUSION: Hysteroscopic cold knife separation can improve the efficacy of IUA and protect the endometrium.

Jin, X.-X., et al. (2022). "Thyroidectomy Using the Lateral Cervical Small Incision Approach for Early Thyroid Cancer." Clinical, cosmetic and investigational dermatology 15: 713-720.
	Objective: Surgical resection is the main treatment for thyroid cancer, but while traditional open thyroidectomy improves prognosis, it also results in poor cosmetic outcomes. Therefore, we devised the lateral cervical small incision approach to thyroidectomy and will evaluate its efficacy.; Methods: The clinicopathological data of 191 patients who underwent unilateral thyroidectomy and isthmusectomy for early thyroid cancer were collected retrospectively. Of these, 100 patients underwent a traditional thyroidectomy using the median cervical approach (control group), and 91 patients underwent a thyroidectomy using the lateral cervical small incision approach (experimental group). The differences in perioperative prognosis, postoperative complications, and cosmetic outcomes between the two groups were evaluated.; Results: There was no significant difference in sex, age, tumor size, lymph node dissection, number of metastases, or postoperative complications between the experimental group and the control group (P > 0.05). There were significant differences in the duration of the operation; postoperative blood loss, drainage, and hospital stay; and scar color, blood circulation, hardness, and thickness between the groups (P < 0.05). The cosmetic outcomes of the incisions in the experimental group were more satisfactory than in the control group (P < 0.05).; Conclusion: When compared with traditional open thyroidectomy, the lateral cervical small incision approach has a lower incidence of complications, a better perioperative prognosis, and an improved cosmetic outcome.; Competing Interests: The authors declare that they have no competing interests. (© 2022 Jin et al.)

Jindal, P. C. and M. Singh (2021). "A comparative RCT of Intrauterine-GCSF versus Subcutaneous-GCSF in Thin Endometrium in IVF-ICSI Cycles." Human reproduction (Oxford, England) 36(SUPPL 1): i294.
	Study question: Does GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to GCSF by the subcutaneous route, in IVF‐ICSI Cycles? Summary answer: Yes, GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to subcutaneous‐GCSF, in ART Cycles? What is known already: GCSF, is a member of the colony stimulating factor family of cytokines and growth factors. GCSF receptors are expressed in high concentration on dominant follicle, particularly at preovulatory stage.The endometrium also shows an increased expression of these receptors. GCSF concentration rises in the follicular fluid at the same time. Serum levels of GCSF are found to be in direct correlation with levels of GCSF in follicular fluid. Serum levels increase progressively from the day the embryo‐transfer to the day of implantation. GCSF has been found to be beneficial in patients with thin endometrium and recurrent implantation failure. Study design, size, duration: This was a RCT conducted between 2018‐ 2019. 30 patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of two doses were administered. Patients undergoing frozen embryo transfer were recruited in the study, after meeting the inclusion and exclusion criteria. Primary outcome measured was increase in endometrium thickness and the secondary outcome was the clinical pregnancy rate and abortion‐rate. Participants/materials, setting, methods: 60 patients with thin endometrium were randomly divided into two groups. Group A: Inj. GCSF (300 mcg/1 ml) subcutaneously on Day 14 onwards alternate days for two doses. Group B: Inj. GCSF (300 mcg/1 ml) instilled slowly into the uterine cavity using an intrauterine insemination (IUI) catheter under USG guidance. Endometrial thickness was assessed after 48 h. If endometrial thickness was found to be <7 mm, a second infusion of GCSF was carried out. Main results and the role of chance: In the subcutaneous group (group‐A) the mean endometrial thickness before GCSF injection was 5.8 ± 0.6 mm and, after injection it increased to 6.9 ± 0.4 mm. Similarly, in the intrauterine group (group‐B) the mean endometrial thickness before GCSF was 5.9 ± 0.7 which increased to a mean of 7.9 ± 0.5 after GCSF instillation. The difference between endometrial thickness before and after intrauterine infusion of GCSF was more than that in the subcutaneous group. In group‐A, 08 patients conceived out of 30 patients ( clinical pregnancy rate 26.6%) and in group B 11 conceived out of 30 patients in whom GCSF was instilled intrauterine (pregnancy rate 36.6%). Thus, there was a difference in the clinical pregnancy rate in the two groups, the intrauterine group yielding a higher clinical pregnancy rate, but it was not statistically significant. Because of the thin endometrium, we found an abortion rate of 25% (2/8) in the subcutaneous‐GCSF group, and an abortion rate of 18% (2/11) in the intrauterine GCSF group. Limitations, reasons for caution: There are few potential limitations because of the small sample size. Confounders such as obesity, smoking and alcohol intake, presence of adenomyosis and endometriosis, were not taken into consideration. Though prevalence of obesity is usually low in Indian women. Habits of smoking and alcohol are exceedingly uncommon in Indian women. Wider implications of the findings: Use of GCSF plays an important role in management of patients of thin endometrium undergoing embryo transfer. It is an easily available and economical preparation in developing countries and the intrauterine instillation of GCSF can be easily practiced in an ART unit with good results in resistant thin endometrium patients.

jindan, w. and w. guiping (2023). "Meta-analysis of efficacy and safety of dienogest in the treatment of adenomyosis."
	
Jing, H., et al. (2021). "Neoadjuvant chemotherapy combined with radical surgery for stage IB2/IIA2 cervical squamous cell carcinoma: a prospective, randomized controlled study of 35 patients." World Journal of Surgical Oncology 19(1): 209.
	OBJECTIVE: This study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery. METHODS: A total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group (n = 35) and the control group (n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated. RESULTS: Only one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups (P > 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group (P < 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group (P > 0.05). CONCLUSIONS: Neoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.

Jing, W., et al. (2022). "The effectiveness of mind-body therapies on quality of life, psychological distress and other health outcomes in women diagnosed with gynaecological cancer: A systematic review and meta-analysis."
	
Jinghua, S., et al. (2021). "Effect and safety of Drospirenone and Ethinylestradiol Tablets (Ⅱ) for dysmenorrhea: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Jingru, W., et al. (2021). "Efficacy and safety of acupuncture for adenomyosis:a protocol for systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
jingyi, h., et al. (2022). "A meta-analysis of non-drug interventions to improve the perimenopausal insomnia network." PROSPERO International prospective register of systematic reviews.
	
Jingyi, H. E., et al. (2023). "Efficacy of Non-pharmacological Interventions to Improve Perimenopausal Insomnia Symptoms: a Network Meta-analysis." Chinese General Practice 26(31): 3963.
	Background The presence of insomnia symptoms reduces the quality of li...

Jiskoot, G., et al. (2022). "Cognitive behavioural therapy for depression in women with PCOS: systematic review and meta-analysis." Reproductive Biomedicine Online 45(3): 599-607.
	Polycystic ovary syndrome (PCOS) is a common endocrine disorder with physical and psychological complaints, especially high depression scores. Cognitive behavioural therapy (CBT) is the first-line psychological treatment for depression. The objective of this study was to examine the effect of different types of CBT interventions and the effects on depression scores in women with PCOS. A literature search was performed in six databases up to July 2020. Studies published in English, in which depression scores were compared between groups during a CBT intervention in women with PCOS, were included. A total of 4854 studies were identified, of which eight studies were included in the systematic review and five in the meta-analysis. CBT ranged from 8 to 52 weeks and involved between 8 and 20 sessions. An overall Cohen's d effect size of 1.02 (95% confidence interval 0.02-2.02) was found in favour of CBT compared with standard care. To conclude, most psychological interventions applying CBT are effective in lowering depression scores in women with PCOS. These results should be interpreted with caution due to methodological differences and quality of the studies. More clinical trials are needed to assess how many sessions of CBT are necessary to treat depression in women with PCOS. (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Jochum, F., et al. (2020). "Three and Five-Year Mortality in Ovarian Cancer after Minimally Invasive Compared to Open Surgery: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 9(8).
	As regards ovarian cancer, the use of minimally invasive surgery has steadily increased over the years. Reluctance persists, however, about its oncological outcomes. The main objective of this meta-analysis was to compare the three and five-year mortality of patients operated by minimally invasive surgery (MIS) for ovarian cancer to those operated by conventional open surgery (OPS), as well as their respective perioperative outcomes. PubMed, Cochrane library and CinicalTrials.gov were systematically searched, using the terms laparoscopy, laparoscopic or minimally invasive in combination with ovarian cancer or ovarian carcinoma. We finally included 19 observational studies with a total of 7213 patients. We found no statistically significant difference for five-year (relative risk (RR) = 0.89, 95% CI 0.53-1.49, p = 0.62)) and three-year mortality (RR = 0.95, 95% CI 0.80-1.12, p = 0.52) between the patients undergoing MIS and those operated by OPS. When five and three-year recurrences were analyzed, no statistically significant differences were also observed. Analysis in early and advanced stages subgroups showed no significant difference for survival outcomes, suggesting oncological safety of MIS in all stages. Whether the surgery was primary or interval debulking surgery in advanced ovarian cancer, did not influence the comparative results on mortality or recurrence. Although the available studies are retrospective, and mostly carry a high risk for bias and confounding, an overwhelming consistency of the evidence suggests the likely effectiveness of MIS in selected cases of ovarian cancer, even in advanced stages. To validate the use of MIS, the development of future randomized interventional studies should be a priority.

Joe, G., et al. (2022). "Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pelvic Pain: A Systematic Review."
	
Joerger, M., et al. (2023). "Safety and anti-tumor activity of lisavanbulin administered as 48-hour infusion in patients with ovarian cancer or recurrent glioblastoma: a phase 2a study." Investigational New Drugs 41(2): 267-275.
	Purpose: Lisavanbulin (BAL101553) is the prodrug of avanbulin (BAL27862), a microtubule-destabilizing agent. The goal of this study (NCT02895360) was to characterize the safety, tolerability and antitumor activity of lisavanbulin administered as a 48-hour intravenous (IV) infusion at the recommended Phase 2 dose (RP2D) of 70 mg/m 2 . Results from the Phase 1 dose-escalation portion of the study identifying the RP2D have been previously reported. Here, we present the findings from the Phase 2a portion of this study. Methods. This multi-center, open-label study included patients with ovarian, fallopian-tube, or primary peritoneal cancer that was either platinum-resistant or refractory (11 patients), or with first recurrence of glioblastoma (12 patients). Lisavanbulin was administered as a 48-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle. Results. Lisavanbulin was well tolerated in both patient cohorts. Thirteen patients (56.5%) developed 49 adverse events assessed as related to study treatment. The majority were mild or moderate; four were grade 3/4. Sixteen SAEs were reported in nine patients (39.1%), with none considered related to study treatment. No AEs led to permanent treatment discontinuation. Three patients in the ovarian cancer cohort had stable disease with lesion size reductions after two cycles of treatment; in the glioblastoma cohort, one patient showed partial response with a > 90% glioblastoma area reduction as best response, and one patient had stable disease after eight cycles of treatment. Conclusion. This study demonstrated a favorable safety and tolerability profile of 48-hour continuous IV infusion of lisavanbulin in patients with solid extracranial tumors or glioblastoma. Clinicaltrials.gov registration: NCT02895360. (© 2023. The Author(s).)

Johannessen, H. H., et al. (2021). "Regular antenatal exercise including pelvic floor muscle training reduces urinary incontinence 3 months postpartum-Follow up of a randomized controlled trial." Acta Obstetricia et Gynecologica Scandinavica 100(2): 294-301.
	INTRODUCTION: Urinary incontinence is a frequently reported condition among women with pregnancy and delivery as established risk factors. The aims of this study were to evaluate the effect of an antenatal exercise program including pelvic floor muscle training on postpartum urinary incontinence, and to explore factors associated with urinary incontinence three months postpartum. MATERIAL AND METHODS: This is a short-term follow-up and secondary analysis of a randomized controlled trial conducted at two Norwegian University Hospitals including healthy, pregnant women aged >18 years with a singleton live fetus. Women in the exercise group received a 12-week standardized exercise program including pelvic floor muscle training, with once weekly group exercise classes led by a physiotherapist and twice weekly home exercise sessions. The controls received standard antenatal care. Data were obtained from questionnaires answered in pregnancy weeks 18-22, and three months postpartum. Urinary incontinence prevalence in the exercise and control groups was compared, and multivariable logistic regression analyses were applied. Urinary incontinence prevalence three months postpartum was assessed by the Sandvik severity index. RESULTS: Among the 722 (84%) women who responded three months postpartum, significantly fewer women in the exercise group (29%) reported urinary incontinence compared with the standard antenatal care group (38%, P = .01). Among women who were incontinent at baseline, 44% and 59% (P = .014) were incontinent at three months postpartum in the exercise and control groups, respectively. Urinary incontinence three months postpartum was associated with age (OR 1.1, 95% CI 1.0-1.1), experiencing urinary incontinence in late pregnancy (OR 3.6, 95% CI 2.3-5.9), birthweight ≥4000 g (OR 1.8, 95% CI 1.2-2.8), and obstetric anal sphincter injuries (OR 2.6, 95% CI 1.1-6.1). Cesarean section significantly reduced the risk of urinary incontinence three months postpartum compared with spontaneous vaginal delivery (OR 0.2, 95% CI 0.1-0.5). CONCLUSIONS: A moderate-intensity exercise program including pelvic floor muscle training reduced prevalence of urinary incontinence 3 months postpartum in women who were incontinent at baseline.

Johnson Jennifer, E., et al. (2023). "Study protocol for the ROSE Scale-Up Study: Informing a decision about ROSE as universal postpartum depression prevention." Contemporary Clinical Trials 132: 107297.
	Purpose: To examine the effectiveness, cost-outcome, equity, scalability, and mechanisms of the Reach Out, Stay strong, Essentials for mothers of newborns (ROSE) postpartum depression prevention (PPD) program as universal versus selective or indicated prevention.; Background: The United States Preventive Services Task Force (USPSTF) currently recommends PPD prevention for pregnant people at risk of PPD (i.e., selective/indicated prevention). However, universal prevention may be more scalable, equitable, and cost-beneficial.; Design: Effectiveness of ROSE for preventing PPD among people at risk is known. To assess ROSE as universal prevention, we need to determine the effectiveness of ROSE among all pregnant people, including those screening negative for PPD risk. We will enroll 2320 pregnant people, assess them with commonly available PPD risk prediction tools, randomize everyone to ROSE or enhanced care as usual, and assess ROSE as universal, selective, and indicated prevention in terms of: (1) effectiveness (PPD prevention and functioning), (2) cost-benefit, (3) equity (PPD cases prevented by universal prevention that would not be prevented under selective/indicated for minority vs. non-Hispanic white people), (4) quantitative and qualitative measures of scalability (from 98 agencies previously implementing ROSE), (5) ROSE mechanisms across risk levels. We will integrate results to outline pros and cons of the three prevention approaches (i.e., universal, selective, indicated).; Conclusion: This will be the first trial to assess universal vs. selective/indicated PPD prevention. Trial design illustrates a novel, efficient way to make these comparisons. This trial, the largest PPD prevention trial to date, will examine scalability, an understudied area of implementation science.; Competing Interests: Declaration of Competing Interest The authors have no competing interests. (Copyright © 2023. Published by Elsevier Inc.)

Johnson, M., et al. (2022). "ARRY-382 in Combination with Pembrolizumab in Patients with Advanced Solid Tumors: Results from a Phase 1b/2 Study." Clinical cancer research : an official journal of the American Association for Cancer Research 28(12): 2517-2526.
	Purpose: ARRY-382 (PF-07265804) is a selective inhibitor of colony-stimulating factor-1 receptor. We evaluated the safety and preliminary efficacy of ARRY-382 plus pembrolizumab in patients with advanced solid tumors.; Patients and Methods: This was an open-label, multicenter, Phase 1b/2 study (NCT02880371) performed over September 1, 2016 to October 24, 2019. In the Phase 1b dose-escalation, patients with selected advanced solid tumors received ARRY-382 [starting dose 200 mg once daily (QD) orally] plus pembrolizumab [2 mg/kg intravenously (IV) every 3 weeks (Q3W)]. Phase 2 patients had: Pancreatic ductal adenocarcinoma (PDA); programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) inhibitor-refractory (PD-1/PD-L1 IR) advanced solid tumors; or platinum-resistant ovarian cancer (prOVCA). Patients received ARRY-382 at the maximum tolerated dose (MTD) of 300 mg QD plus pembrolizumab 200 mg IV Q3W.; Results: Primary endpoints of dose-limiting toxicities (DLT; Phase 1b) and objective response rate (Phase 2) were met. In Phase 1b, 19 patients received ARRY-382 200-400 mg. Three patients reported DLTs. The MTD of ARRY-382 (plus pembrolizumab) was 300 mg QD. In Phase 1b, 2 patients (10.5%) had confirmed partial response (PR): 1 with PDA and 1 with ovarian cancer, lasting 29.2 and 3.1 months, respectively. In Phase 2, there were 27, 19, and 11 patients in the PDA, PD-1/PD-L1 IR, and prOVCA cohorts, respectively. One patient (3.7%) with PDA had a PR lasting 2.4 months. The most frequent ARRY-382-related adverse events were increased transaminases (10.5%-83.3%) and increased creatine phosphokinase (18.2%-50.0%).; Conclusions: Although limited clinical benefit was observed, ARRY-382 plus pembrolizumab was well tolerated. (©2022 The Authors; Published by the American Association for Cancer Research.)

Johnson Melissa, L., et al. (2023). "A Phase Ib Dose-Escalation Study of LCL161 Plus Oral Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer and Select Gynecologic Malignancies." The Oncologist 28(7): 640.
	Background: This was an open-label, multicenter, single-arm phase Ib dose-escalation study of oral LCL161 administered in combination with oral topotecan in patients with relapsed/refractory small cell lung cancer (SCLC) and select gynecological cancers.; Methods: Cohorts of 3-6 patients initiated treatment with LCL161 and topotecan in escalating doses. LCL161 was administered orally on days 1, 8, and 15 of each 21-day cycle; topotecan was administered orally for the first 5 days of each 21-day cycle.; Results: A total of 35 patients were enrolled in 6 cohorts; 30 patients were female; 4 patients had SCLC and 19 patients had ovarian cancer. Median prior lines of therapy were 3 (1-10). Median duration of treatment was 7.1 weeks (0.1-174). The most frequent grade 3/4 treatment-related adverse events were thrombocytopenia (51.43%) and anemia (31.43%). ORR was 9.7%; 58% of patients had SD. The study was stopped early before the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) were determined.; Conclusion: The addition of LCL161 to oral topotecan caused more myelosuppression when dosed together than what was associated with either drug alone. Moreover, the drug combination did not improve outcomes. The study was terminated early (ClinicalTrials.gov Identifier: NCT02649673). (© The Author(s) 2023. Published by Oxford University Press.)

Johnson, Y. Y. L., et al. (2022). "The 'Empty Pelvis Syndrome': A systematic review of reconstruction techniques and their associated complications." Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 24(1): 16-26.
	AIM: 'Empty pelvis syndrome' is a major contributor to morbidity following pelvic exenteration. Several techniques aimed at filling the pelvis have been proposed, however, there is no consensus on the best approach. We evaluated and compared the complications associated with each reconstruction technique to determine which is associated with the lowest incidence of complications related to the 'empty pelvis'. METHODS: The systematic review protocol was prospectively registered with PROSPERO (CRD42021239307). PRISMA-P guidelines were used to present the literature. PubMed and MEDLINE were systematically searched up to 1st February 2021. A dataset containing predetermined primary and secondary outcomes was extracted. RESULTS: Eighteen studies including 375 patients fulfilled our criteria, with mainly rectal and gynaecological cancer participants. Only three studies had a follow-up greater than two years. Six surgical interventions were identified. Mesh reconstruction and breast prosthesis were associated with low rates of small bowel obstruction (SBO), enterocutaneous fistulas and perineal hernia. Findings for myocutaneous flaps were similar however they were associated with high rates of perineal wound complications. Omentoplasty was found to have a high perineal wound infection rate (40%). Obstetric balloons were found to have the highest rates of perineal wound dehiscence and SBO. Silicone expanders effectively kept small bowel out of the pelvis though rates of pelvic collections remained high (20%). CONCLUSION: The morbidity associated with the empty pelvis remains considerable. Given the low-quality evidence with small patient numbers, strong conclusions in favour of a certain technique and comparing these interventions remains challenging.

Johnston, K. E., et al. (2023). "Developing the use of electronic patient reported outcomes to implement dietetic intervention for a pilot survivorship clinic for women diagnosed with breast and gynaecological cancer in ireland: The women's health initiative LYSA study." Clinical Nutrition ESPEN 58: 465.
	Rationale: Diet has been reported to be a key component to optimal outcomes in cancer patients and survivors1. Due to the increasing number of cancer survivors, the need to develop innovative pathways of co-ordinated care to manage the nutrition-related symptoms and side effects of treatment has never been more pertinent. Method(s): The Women's Health Initiative LYSA Study is a randomised control trial assessing the feasibility of a survivorship clinic with a dietetic intervention for women with early-stage breast and gynaecologic cancer post primary therapy. The intervention incorporates symptom management through ePRO collection every 2 months for 1 year facilitated by Castor EDC. The ePRO assesses Malnutrition Screening Tool, body weight and physical activity. Participants partake in nutritional and physical assessments, including body composition analysis at baseline and endpoints. The participants have access to a trigger-initiated nutritional management pathway, with individualised nutritional counselling on a telehealth platform for worsening or severe triggers. Result(s): Through the first survivorship clinic of its kind in Ireland, an innovative symptom monitoring system and telehealth platforms, co-ordinated pathways of care were developed for this growing cohort. The survivorship clinic opened in March 2021, and at time of submission, N=200 baseline visits had been completed, and 95 endpoint visits had been completed. The final endpoint visits are projected to be complete by October 2023. Conclusion(s): The assessment of the feasibility of the use of ePROs to implement dietetic intervention for a pilot survivorship clinic in Ireland is ongoing. References: 1 WCFR/AICR. Diet, nutrition, physical activity, and cancer: a global perspective. Continuous Update Project Expert Report. 2018 Disclosure of Interest: None declaredCopyright © 2023

Joly, F., et al. (2022). "A phase II study of Navitoclax (ABT-263) as single agent in women heavily pretreated for recurrent epithelial ovarian cancer: The MONAVI - GINECO study." Gynecologic Oncology 165(1): 30-39.
	Background: There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-x L anti-apoptotic protein inhibitor, in chemo-resistant ovarian cancer cells and tumors, suggesting its potential activity in platinum-resistant patients.; Methods: We conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors. Navitoclax was administered at the daily dose of 150 mg during a lead-in period (7-14 days) and then increased to 250 mg daily in the absence of dose-limiting thrombocytopenia (<G3). Progression-free survival (PFS) based on RECIST v1.1 criteria was the primary endpoint. Analysis of efficacy according to the expression of Bcl-2 family proteins in tumor biopsies was also planned.; Results: The 3-month PFS was 22.7% [ 95% CI: 13.2-39.2], median PFS was 1.64 months [ 95% CI: 1.58-2.30]. There were 16 (35.6%, 95% CI: 22.3-51.3) overall responses (RECIST v1.1): 1 partial response and 15 stable diseases. No correlation between the expression of Bim, Mcl-1 and P-ERK with clinical response was found in this study. Thrombocytopenia was the major side-effect (G3/4: n = 12; 26%), leading to pursue at the daily dose of 150 mg in 8 patients and to discontinue treatment in 3 patients. Neither significant bleeding nor toxic death were observed.; Conclusions: Navitoclax monotherapy had poor activity that was not correlated with the expression of Bim, Mcl-1 and P-ERK, without unacceptable toxicity.; Trial Registration: Clinicaltrials.gov identifier: NCT02591095.; Competing Interests: Declaration of Competing Interest F. Joly: Abbvie for Navitoclax provision, consulting for Roche, GSK, Astra Zeneca, Clovis, MSD, Ipsen, Janssen, Astellas, Pfizer, Sanofi, BMS, Bayer. M. Fabbro: Consulting for GSK, Astra-Zeneca, and Clovis Oncology. P. Follana: GSK, Astra Zeneca, Clovis, MSD, Novartis, DAIICHI. J.S. Frenel: Consulting for Novartis, Pfizer, Astra Zeneca, Lilly, Roche, BIOCAD, DAIICHI, GSK-Tesaro, Pierre Fabre, and Clovis oncology. B.You: Consulting for MSD, Astra-Zeneca, GSK-TESARO, BAYER, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, and Myriad. J. Lequesne, J. Medioni, A. Lesoin, S. Abadie-Lacourtoisie, A. Floquet, L. Gladieff, C. Gavoille, E. Kalbacher, M. Briand, P.E. Brachet, F. Giffard, L-B. Weiswald, P.A. Just, C. Blanc-Fournier, A. Leconte, B. Clarisse, A. Leary, L. Poulain: no conflicts of interest to disclose in relation with this work. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Jones Kimberley, A., et al. (2023). "Interventions from pregnancy to two years after birth for parents experiencing complex post-traumatic stress disorder and/or with childhood experience of maltreatment." The Cochrane Database of Systematic Reviews 5: CD014874.
	Background: Acceptable, effective and feasible support strategies (interventions) for parents experiencing complex post-traumatic stress disorder (CPTSD) symptoms or with a history of childhood maltreatment may offer an opportunity to support parental recovery, reduce the risk of intergenerational transmission of trauma and improve life-course trajectories for children and future generations. However, evidence relating to the effect of interventions has not been synthesised to provide a comprehensive review of available support strategies. This evidence synthesis is critical to inform further research, practice and policy approaches in this emerging area.; Objectives: To assess the effects of interventions provided to support parents who were experiencing CPTSD symptoms or who had experienced childhood maltreatment (or both), on parenting capacity and parental psychological or socio-emotional wellbeing.; Search Methods: In October 2021 we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, together with checking references and contacting experts to identify additional studies.; Selection Criteria: All variants of randomised controlled trials (RCTs) comparing any intervention delivered in the perinatal period designed to support parents experiencing CPTSD symptoms or with a history of childhood maltreatment (or both), to any active or inactive control. Primary outcomes were parental psychological or socio-emotional wellbeing and parenting capacity between pregnancy and up to two years postpartum.; Data Collection and Analysis: Two review authors independently assessed the eligibility of trials for inclusion, extracted data using a pre-designed data extraction form, and assessed risk of bias and certainty of evidence. We contacted study authors for additional information as required. We analysed continuous data using mean difference (MD) for outcomes using a single measure, and standardised mean difference (SMD) for outcomes using multiple measures, and risk ratios (RR) for dichotomous data. All data are presented with 95% confidence intervals (CIs). We undertook meta-analyses using random-effects models.; Main Results: We included evidence from 1925 participants in 15 RCTs that investigated the effect of 17 interventions. All included studies were published after 2005. Interventions included seven parenting interventions, eight psychological interventions and two service system approaches. The studies were funded by major research councils, government departments and philanthropic/charitable organisations. All evidence was of low or very low certainty. Parenting interventions Evidence was very uncertain from a study (33 participants) assessing the effects of a parenting intervention compared to attention control on trauma-related symptoms, and psychological wellbeing symptoms (postpartum depression), in mothers who had experienced childhood maltreatment and were experiencing current parenting risk factors. Evidence suggested that parenting interventions may improve parent-child relationships slightly compared to usual service provision (SMD 0.45, 95% CI -0.06 to 0.96; I 2 = 60%; 2 studies, 153 participants; low-certainty evidence). There may be little or no difference between parenting interventions and usual perinatal service in parenting skills including nurturance, supportive presence and reciprocity (SMD 0.25, 95% CI -0.07 to 0.58; I 2 = 0%; 4 studies, 149 participants; low-certainty evidence). No studies assessed the effects of parenting interventions on parents' substance use, relationship quality or self-harm. Psychological interventions Psychological interventions may result in little or no difference in trauma-related symptoms compared to usual care (SMD -0.05, 95% CI -0.40 to 0.31; I 2 = 39%; 4 studies, 247 participants; low-certainty evidence). Psychological interventions may make little or no difference compared to usual care to depression symptom severity (8 studies, 507 participants, low-certainty evidence, SMD -0.34, 95% CI -0.66 to -0.03; I 2 = 63%). An interpersonally fo used cognitive behavioural analysis system of psychotherapy may slightly increase the number of pregnant women who quit smoking compared to usual smoking cessation therapy and prenatal care (189 participants, low-certainty evidence). A psychological intervention may slightly improve parents' relationship quality compared to usual care (1 study, 67 participants, low-certainty evidence). Benefits for parent-child relationships were very uncertain (26 participants, very low-certainty evidence), while there may be a slight improvement in parenting skills compared to usual care (66 participants, low-certainty evidence). No studies assessed the effects of psychological interventions on parents' self-harm. Service system approaches One service system approach assessed the effect of a financial empowerment education programme, with and without trauma-informed peer support, compared to usual care for parents with low incomes. The interventions increased depression slightly (52 participants, low-certainty evidence). No studies assessed the effects of service system interventions on parents' trauma-related symptoms, substance use, relationship quality, self-harm, parent-child relationships or parenting skills.; Authors' Conclusions: There is currently a lack of high-quality evidence regarding the effectiveness of interventions to improve parenting capacity or parental psychological or socio-emotional wellbeing in parents experiencing CPTSD symptoms or who have experienced childhood maltreatment (or both). This lack of methodological rigour and high risk of bias made it difficult to interpret the findings of this review. Overall, results suggest that parenting interventions may slightly improve parent-child relationships but have a small, unimportant effect on parenting skills. Psychological interventions may help some women stop smoking in pregnancy, and may have small benefits on parents' relationships and parenting skills. A financial empowerment programme may slightly worsen depression symptoms. While potential beneficial effects were small, the importance of a positive effect in a small number of parents must be considered when making treatment and care decisions. There is a need for further high-quality research into effective strategies for this population. (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Jones, R., et al. (2023). "A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 29(2): 331-340.
	Purpose: This was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), pharmacokinetics profile, and clinical activity of SRA737.; Patients and Methods: Patients with advanced solid tumors were enrolled into dose-escalation cohorts and treated in 28-day cycles with oral SRA737 on days 2, 3, 9, 10, 16, and 17, and intravenous gemcitabine on days 1, 8, and 15. Treatment was continued until progression. Each expansion cohort included up to 20 patients with specific genetically defined tumors.; Results: The RP2D was determined to be 500 mg SRA737 combined with low-dose (250 mg/m2) gemcitabine. Of 143 enrolled patients, 77 were treated at doses of at least 500 mg SRA737 combined with 250 mg/m2 gemcitabine. Common toxicities of nausea, vomiting, fatigue, and diarrhea were primarily mild to moderate, and rarely led to treatment discontinuation. Anemia, neutropenia, and thrombocytopenia were grade ≥3 in 11.7%, 16.7%, and 10% of patients treated at the RP2D, respectively. The objective response rate (ORR) was 10.8% overall and notably the ORR in anogenital cancer was 25%. Partial tumor responses were observed in anogenital cancer, cervical cancer, high-grade serous ovarian cancer, rectal cancer, and small cell lung cancer.; Conclusions: SRA737 in combination with low-dose gemcitabine was well tolerated with lower myelotoxicity than has been seen at standard doses of gemcitabine or with other combinations of Chk1 inhibitors with gemcitabine. Tumor responses were observed in anogenital and other solid tumors. (©2022 The Authors; Published by the American Association for Cancer Research.)

Jones, S., et al. (2023). "PIPAC IN CANCERS OF THE COLON, OVARY AND STOMACH (THE PICCOS TRIAL)." Pleura and Peritoneum 8(1): A36-A37.
	Introduction: In 2021 the National Institute for Clinical Excellence (NICE) published interventional procedures guidance that stipulated that in the UK, Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC) should only be used within the context of a randomised control trial to demonstrate efficacy against standard of care. The UK PIPAC collaborative would like to present its first randomised controlled trial assessing the efficacy of PIPAC in the management of peritoneal metastases (PM) in patients with cancer of the colon, ovary and stomach. The PICCOS trial aims to not only assess efficacy compared to standard of care in terms of progression free survival (PFS), but also quality of life. Method(s): This is a basket, phase II trial with a master protocol covering the overarching research methodology, and embedded individual cancer site specific protocols, sample sizes and analysis plans. 78 patients with PM from colon cancer, 62 patients with PM from ovarian cancer and 72 patients with PM from stomach cancer will be randomised to systemic chemotherapy or alternating PIPAC and systemic chemotherapy every 2 or 3 weeks for 18 weeks in total. The primary outcome measure is PFS. CT scans undertaken every 8 weeks following treatment will be assessed against the RECIST criteria to assess disease burden and determine PFS. Quality of life will be assessed using the EORTC QLQ C30 tool. Result(s): The PICCOS Trial has now secured funding with a National Institute of Health Research Efficacy and mechanism Evaluation (NIHR EME) grant and is due to commence in November 2022 with a four-year running period. Publication and dissemination of results is anticipated in 2027. Conclusion(s): This is the first UK randomized controlled trial assessing the efficacy and impact of quality of life of PIPAC in the treatment of peritoneal metastases aiming to provide high quality evidence to guide clinical practice and further research in the future.

Jones, T., et al. (2021). "Lavender Aromatherapy to Reduce Anxiety During Intrauterine Insemination: A Randomized Controlled Trial." Global advances in health and medicine 10: 21649561211059074.
	BACKGROUND: Infertility is a global public health issue. Therapies such as intrauterine insemination (IUI) are effective but may be associated with considerable anxiety. Preliminary data suggest that decreasing this anxiety might lead to improved outcomes. OBJECTIVE: To determine whether lavender aromatherapy (LA) reduces anxiety during an IUI procedure. METHODS: A randomized controlled trial of women undergoing IUI at a hospital-based fertility clinic. The intervention and comparison were the use of LA vs water. Measurements were the change in anxiety level during an IUI procedure, with secondary assessment of pain scores, patient satisfaction, and pregnancy rates. RESULTS: In total, 67 women were screened, and 62 women randomly assigned to either placebo (n = 31) or LA (n = 31). No differences were observed in baseline demographic characteristics or visual analog scores for anxiety before IUI (mean [95% CI], 33.9 [25.2 to 45.6] mm vs 41.0 [33.0 to 49.0] mm) in the LA and placebo groups. However, a statistically significant change in anxiety was observed after LA inhalation during the procedure (mean [95% CI], -11.2 [-19.1 to -3.2]) compared with placebo (mean [95% CI], 1.3 [-5.6 to 8.2]; P = .02). No significant difference was observed in pain during IUI in the LA group vs placebo group. Patient satisfaction was high, with 93% of respondents in the LA group satisfied with the aromatherapy during their procedure. Additionally, 76% of participants who received placebo reported that they would prefer to use LA during their IUI. No statistically significant difference was detected in pregnancy rates between the 2 groups: 19.4% with LA vs 9.7% with placebo (P = .47). CONCLUSION: LA reduced anxiety and was preferred by women during IUI fertility treatments.

Jones Tamara, L., et al. (2020). "Physical activity and exercise in women with ovarian cancer: A systematic review." Gynecologic Oncology 158(3): 803-811.
	Objective: A consistent body of evidence supports participating in physical activity (PA) post-cancer diagnosis as beneficial to function, quality-of-life and potentially survival. However, diagnosis of late stage disease, poor prognosis, receipt of high doses of adjuvant therapy and presence of severe acute and persistent treatment-related side-effects may alter how these findings translate to women with ovarian cancer. Therefore, the objectives of this review were to (I) describe PA levels post-diagnosis of ovarian cancer, (II) explore the relationship between PA levels and health outcomes, and (III) evaluate the effect of exercise interventions for women with ovarian cancer.; Methods: PubMed, EMBASE, Scopus and CINAHL were systematically searched to December 31, 2019. Two independent reviewers assessed articles for eligibility. Studies were eligible if they evaluated the relationship between PA levels or an exercise intervention and health outcomes following ovarian cancer. Methodological quality was assessed by two independent reviewers using the Joanna Briggs Institute Critical Appraisal Tools. Descriptive statistics were used to collate relevant data.; Results: 34 articles were eligible for inclusion. Results demonstrated that most women decrease PA from pre- to post-diagnosis and remain insufficiently active following diagnosis. Higher levels of PA were associated with higher health-related quality-of-life (HRQOL), and lower levels of anxiety and depression. Exercise appears safe and feasible during and following treatment and leads to improvements in HRQOL, fatigue and additional physical and psychological outcomes.; Conclusions: Findings suggest that PA is relevant to health outcomes for women with ovarian cancer. Interventions that aid women to stay or become sufficiently active, including through exercise interventions during or following treatment have potential to improve the lives of those with ovarian cancer. Future work evaluating targeted interventions that can accommodate disease-specific challenges is now required to ensure scientific findings can translate into improved ovarian cancer care.; Competing Interests: Declaration of Competing Interest All authors declare they have no conflicts of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Jones, T. L., et al. (2020). "Physical Activity and Exercise in Women with Ovarian Cancer: A Systematic Review." Obstetrical and Gynecological Survey 75(10): 606-607.
	(Abstracted from Gynecol Oncol 2020;158:803-811) Treatment for epithelial ovarian cancer may involve debulking surgery, a carboplatin-paclitaxel chemotherapy combination, or more novel approaches such as immunotherapy. There is a significant body of evidence supporting an association between physical activity (PA) and improved quality of life (QOL), physical morbidity, fatigue, depression, and anxiety among patients diagnosed with cancer.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Jooya, A., et al. (2022). "Systematic review of brachytherapy for symptom palliation." Brachytherapy 21(6): 912-932.
	PURPOSE: Brachytherapy is most often applied in the curative or salvage setting, but many forms of brachytherapy can be helpful for symptom palliation. Declining utilization is seen, for multiple reasons, such as lack of awareness, insufficient expertise, or poor access to equipment. High level evidence for many types of palliative brachytherapy has been lacking. The objective of the current study was to review the evidence for utilization and efficacy of brachytherapy to palliate symptoms from cancer. MATERIALS AND METHODS: We performed a systematic search in EMBASE and MEDLINE for English-language articles published from January 1980 to May 2022 that described brachytherapy used for a palliative indication in adults with a diagnosis of cancer (any subtype) and at least one symptom related outcome. Individual case reports and conference abstracts were excluded. All publications were independently screened by two investigators for eligibility. RESULT(S): The initial search identified 3637 abstracts of which 129 were selected for in-depth review. The number of studies (total number of patients) included in the final analysis varied widely by tumor site with the majority (68.2%) involving either lung or esophageal cancer. Despite a limited number of prospective trials that assessed the efficacy of brachytherapy for symptom management, there was a positive effect on palliation of symptoms across all tumor types. There was no clear trend in the number of publications over time. The most commonly cited symptom indications for palliation by brachytherapy were dysphagia, dyspnea, pain and bleeding. CONCLUSION(S): Brachytherapy can provide palliation for patients with advanced cancer, across different tumor sites and clinical scenarios. However, high level evidence in the literature to support palliative applications of brachytherapy is lacking or limited for many tumor sites. There appears to be a strong publication bias towards positive studies in favor of brachytherapy. Beyond anecdotal reports and individual practices, outcomes research can further our understanding of the role of brachytherapy in palliating advanced cancers of all types, and should be encouraged.Copyright © 2022

Jorasz, K., et al. (2023). "Posture Correction Therapy and Pelvic Floor Muscle Function Assessed by sEMG with Intravaginal Electrode and Manometry in Female with Urinary Incontinence." International Journal of Environmental Research and Public Health 20(1): 369.
	Introduction: The aim of the study was to assess the influence of the implemented therapeutic programme, which consisted of body posture correction and of change of habits, on the pelvic floor muscle function in women with stress urinary incontinence. Material(s) and Method(s): The 60 women were randomly divided into two groups: the study population and the clinical control group (subjects received envelopes with numbers of the group: 1- study population aged 38.3 +/- 5.54, 2- clinical control group aged 35.5 +/- 4.7. We used the following research methods: A personal questionnaire with subjects' demographics and with questions related to the type of work, physical activity, childbirths and any issues related to the pelvic floor (pre-test), Pelvic floor muscle assessment with the use of the PERFECT Scheme and the Oxford scale palpation examination, sEMG with intravaginal electrode and manometry with an intravaginal probe-pre-test and post-test. Subjective assessment of body posture in the sagittal plane according to the McKenzie methodology. Result(s): In both groups, VRP (resting vaginal pressure) and resting PFM tension were significantly reduced. The strength and endurance of PFM, tension during MVC and VSP (intravaginal pressure during contraction) increased, with no difference between the groups. SUI decreased significantly, and quality of life improved significantly in both groups. Conclusion(s): Education of the pelvic floor and changing habits significantly affected the activity of PFM and improved the quality of life in the group of patients with SUI. The posture correction therapy with manual therapy and stretching exercises did not increase this effect.Copyright © 2022 by the authors.

Jorge, C. H., et al. (2024). "Pelvic floor muscle training as treatment for female sexual dysfunction: a systematic review and meta-analysis." American Journal of Obstetrics and Gynecology.
	Objective: This study aimed to investigate the efficacy of pelvic floor muscle training in treating female sexual dysfunction. Data Sources: A systematic review of databases, including PubMed, Ovid Medline, CINAHL, Embase, BVSalud, Scopus, and Cochrane Library, was performed in July 2021 and updated in May 2023. Study Eligibility Criteria: Full-text articles of randomized controlled trials comparing pelvic floor muscle training with no intervention or another conservative treatment were included. At least 1 arm of these trials aimed to improve women's sexual function or treat sexual dysfunction. Method(s): The data for this review were extracted and analyzed by 2 independent reviewers. Data on the characteristics of each intervention were extracted using the Consensus on Exercise Reporting Template. The risk of bias and certainty of evidence were assessed using the Physiotherapy Evidence Database (PEDro) scale and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria, respectively. A meta-analysis was conducted considering the posttreatment mean score difference in the Female Sexual Function Index between the control and treatment groups. Result(s): A total of 21 randomized controlled trials were included in this review. The Consensus on Exercise Reporting Template revealed varying quality of the pelvic floor muscle training protocols. Four studies were included in the meta-analysis showing that pelvic floor muscle training improved arousal (1.49; 95% confidence interval, 0.13-2.85), orgasm (1.55; 95% confidence interval, 0.13-2.96), satisfaction (1.46; 95% confidence interval, 0.14-2.77), pain (0.74; 95% confidence interval, 0.11-1.37), and the Female Sexual Function Index overall score (7.67; 95% confidence interval, 0.77-14.57). Very low certainty of evidence due to the data's high clinical and statistical heterogeneity was found according to the GRADE criteria. No side effects of the interventions were reported. Conclusion(s): This systematic review and meta-analysis showed that pelvic floor muscle training improved female Female Sexual Function Index total score and several subscales; however, the certainty of the evidence is low.Copyright © 2024 Elsevier Inc.

Jorgensen, E., et al. (2023). "Evolving best practices in the surgical management of endometriosis - examining the evidence and expert opinion." Current opinion in obstetrics & gynecology 35(4): 383-388.
	Purpose of Review: Endometriosis is a common and often debilitating condition, with multiple theories of pathogenesis. Despite the prevalence of endometriosis, the optimal surgical management remains unclear.; Recent Findings: Laparoscopy is the gold standard for the diagnosis of endometriosis, with biopsy confirmation more accurate than visual diagnosis alone. It is not clear from the existing data whether excision of endometriosis is superior to ablation. Improvement in pain has been documented following peritonectomy, however, controlled trials are lacking. It is not clear whether concomitant hysterectomy improves pain associated with endometriosis, although hysterectomy may reduce reoperation rate. Bilateral oophorectomy performed for the treatment of endometriosis may not be curative without simultaneous excision of all visible lesions, and the risks of surgical menopause should be considered. The rate of appendiceal endometriosis is higher than previously suspected, and may not correlate with intraoperative visual findings, suggesting appendectomy should be considered during surgical treatment of endometriosis.; Summary: Despite the prevalence of endometriosis, there is a paucity of data to guide optimal surgical management. More high-quality studies are needed. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Joris, A., et al. (2024). "Randomized trial: treatment of genitourinary syndrome of menopause using radiofrequency." Climacteric.
	Objective: A randomized controlled study was conducted to evaluate the safety and efficacy of radiofrequency treatment in postmenopausal women not willing to use or presenting a contraindication for menopause hormone therapy (MHT) and suffering from genitourinary syndrome of menopause (GSM). Method(s): A prospective randomized open study evaluated the effect of radiofrequency treatment versus a gel (control group) in postmenopausal women suffering from GSM. Patients were assessed at baseline and after 10-12 weeks of treatment for severity of vulvovaginal atrophy, dyspareunia, pH, vaginal smear maturation index, Vaginal Health Index and Female Sexual Function Index. The difference at baseline and after 10-12 weeks of treatment and the difference in improvement were tested between groups by a two-sample t-test and the Mann-Whitney test. Result(s): Due to the COVID-19 pandemic, we were only able to treat 48 patients (24 patients using radiofrequency and 24 patients using a gel). Globally, at the end of the study, there were no differences in changes of the measured outcomes between the group of women treated with radiofrequency and the control group. Conclusion(s): Radiofrequency treatment was found to be safe, but was not superior to a gel, although the study lacked power. The study was registered at ClinicalTrials.gov (NCT03857893).Copyright © 2024 International Menopause Society.

Jose Claudio Garcia, L., et al. (2023). "Efficacy of dietary interventions in the treatment of endometriosis: a systematic review."
	
Jose, M., et al. (2022). "Maternal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia: a systematic review and meta-analysis."
	
José Rodrigues do, C., et al. (2023). "The impact of different therapies on vaginal atrophy and quality of life in gynecologic cancer patients: a systematic review."
	
Joseph, P., et al. (2023). "Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of non-surgical periodontal treatment in patients with concurrent systemic conditions." Clinical oral investigations 28(1): 21.
	Objective: To conduct a systematic review of the published scientific evidence to evaluate the efficacy of nonsurgical periodontal therapy (NSPT) in treating periodontitis in patients with concurrent systemic conditions (diabetes, CVD, erectile dysfunction, chronic kidney disease, rheumatoid arthritis, polycystic ovarian syndrome, obesity, pregnancy). We hypothesised that NSPT results in better periodontal outcomes when compared to untreated controls after follow-up.; Materials and Methods: A systematic search (PUBMED/EMBASE) was conducted from 1995 to 2023 to identify randomised controlled trials (RCTs) with a minimum follow-up of 3 months. The primary outcome was the difference in mean probing depth (PD), and the secondary outcomes were mean clinical attachment loss (CAL), percentage of sites with PD ≤ 3 mm (%PD ≤ 3 mm) and percentage of sites with bleeding on probing (%BOP) between the treated and untreated control group in patients with comorbidities.; Results: The electronic search resulted in 2,403 hits. After removing duplicates, 1,565 titles and abstracts were screened according to the eligibility criteria, resulting in 126 articles for full-text screening. Following this, 44 studies were analysed. Restricting to studies with low bias or some concerns, NSPT group demonstrated a 0.55 mm lower mean PD (95%CI: -0.69; -0.41) after 3 months compared to the control group.; Conclusion: Compared to the untreated controls, NSPT notably reduced mean PD, mean CAL, and %BOP while increasing %PD ≤ 3 mm in patients with concurrent systemic conditions. These findings suggest that NSPT is also an effective procedure in managing periodontitis in patients with concurrent systemic conditions.; Trial Registration: This systematic review was registered under the protocol registration number CRD42021241517/PROSPERO. (© 2023. The Author(s).)

Joueidi, Y., et al. (2019). "[Uterine preservation or not during prolapse surgery: Review of the literature]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 29(17): 1021-1034.
	OBJECTIVE: To evaluate the impact of hysterectomy in case of genital prolapse on the anatomical and functional results, and on per and post operative complications compared with uterine preservation. MATERIAL AND METHODS: We conducted a review of the Pubmed, Medline, Embase and Cochrane literature using the following terms and MeSH (Medical Subject Headings of the National Library of Medicine): uterine prolapse; genital prolapse; prolapse surgery; vaginal prolapse surgery; abdominal prolapse surgery; hysterectomy; hysteropexy; sacrocolpopexy; surgical meshes; complications; sexuality; neoplasia; urinary; incontinence; cancer. RESULTS: Among the 168 abstracts studied, 63 publications were retained. Whatever performance of hysterectomy or not, anatomical and functional results were similar in abdominal surgery (sacrocolpopexy) (OR=2.21 [95% CI: 0.33-14.67]) or vaginal surgery (OR=1.07 [95% CI: 0.38-2.99]). There was no difference in terms of urinary symptoms or sexuality after surgery. Hysterectomy was associated to a higher morbidity (bleeding, prolonged operating time, longer hospital stay), to an increased risk of mesh exposure particularly in case of total hysterectomy (8.6%; 95% CI: 6.3-11). CONCLUSION: In the absence of evidence of superiority in terms of anatomical and functional outcomes, with an increased rate of complications, concomitant hysterectomy with prolapse surgery should probably not be performed routinely.

Joyce Caroline, M., et al. (2022). "Advances in the diagnosis and early management of gestational trophoblastic disease." BMJ medicine 1(1): e000321.
	Gestational trophoblastic disease describes a group of rare pregnancy related disorders that span a spectrum of premalignant and malignant conditions. Hydatidiform mole (also termed molar pregnancy) is the most common form of this disease. Hydatidiform mole describes an abnormal conceptus containing two copies of the paternal genome, which is classified as partial when the maternal genome is present or complete when the maternal genome is absent. Hydatidiform mole typically presents in the first trimester with irregular vaginal bleeding and can be suspected on ultrasound but confirmation requires histopathological evaluation of the products of conception. Most molar pregnancies resolve without treatment after uterine evacuation, but occasionally the disease persists and develops into gestational trophoblastic neoplasia. Close monitoring of women after molar pregnancy, with regular measurement of human chorionic gonadotrophin concentrations, allows for early detection of malignancy. Given the rarity of the disease, clinical management and treatment is best provided in specialist centres where very high cure rates are achievable. This review looks at advances in the diagnosis and early management of gestational trophoblastic disease and highlights updates to disease classification and clinical guidelines. Use of molecular genotyping for improved diagnostic accuracy and risk stratification is reviewed and future biomarkers for the earlier detection of malignancy are considered.; Competing Interests: Competing interests: We have read and understood the BMJ Medicine policy on declaration of interests and declare the following interests: none. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Joyce, S., et al. (2021). "Effectiveness of pelvic floor muscle training in women with dyspareunia: a systematic review."
	
Jprn, U. (2022). "The effect of chronic intake of Dioscorea esculenta powder on menstrual pain in young women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Participants were administered Dioscorea esculenta (300 mg/day) for 4 weeks during the first trial and, after a 4‐week washout period, the Dioscorea esculenta and placebo groups exchanged their assigned treatments for the second trial. Participants were administered placebo for 4 weeks during the first trial and, after a 4‐week washout period,the Dioscorea esculenta and placebo groups exchanged their assigned treatments for the second trial. CONDITION: Normal healthy adult female PRIMARY OUTCOME: PGE2, COX‐2; MPQ, DRSP INCLUSION CRITERIA:

Jprn, U. (2022). "A study on the effect of childcare support services on QOL and postpartum depression and a examination of services for pregnant and postpartum women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The intervention group will receive the communication robot (BOCCO emo) at 30 weeks of pregnancy after consent is confirmed, and the intervention will start as soon as it arrives. The service will continue to be available until 3 months after delivery. In addition to the parenting support services, online counseling (up to 2 times), online midwife/nursery consultation (up to 2 times), and online medical care (free of charge up to the appointment, actual cost for medical care) are also available. The frequency of use and services can be selected according to the preferences of the research subjects. The control group will not use the parenting support services. CONDITION: Postpartum depression PRIMARY OUTCOME: WHO‐5(simplified Japanese version of the WHO‐Five Well‐being Index) change in total score from baseline to each time point(36 weeks gestation, 1 and 3 months postpartum). SECONDARY OUTCOME: (1)EPDS(Edinburgh Postnatal Depression Scale) change in total score from baseline to each time point.; (2)Number of consultations with local maternal and child health centers(36 weeks gestation, 1 and 3 months postpartum).; (3)Satisfaction with overall service, continued use, recommendation, frequency of use, intention to pay for service, financial knowledge and insurance consultation needs based on questionnaire responses regarding service, etc. INCLUSION CRITERIA:

Jprn, U. (2023). "Evaluation of the effect of flaxseed lignan on menopausal symptoms." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Secoisolariciresinol diglucoside (SDG) capsule (4 capsules per day) Placebo capsule (4 capsules per day) CONDITION: healthy person PRIMARY OUTCOME: The simplified menopausal index (SMI) test Pittsburgh sleep quality index SECONDARY OUTCOME: Questionnaires related to menopausal symptoms INCLUSION CRITERIA:

Jprn, U. (2023). "Relationship between menopausal women's health literacy, work performance, and QOL." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: The intervention group will be sent weekly messages about health issues specific to menopausal women for 8 weeks. No message is sent to the control group. CONDITION: menopausal symptoms PRIMARY OUTCOME: health literacy, health, work performance, QOL INCLUSION CRITERIA:

Jprn, U. (2023). "Verification of the effects of plant extract intake on sexual function and menopausal symptoms." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Continuous intake of test food A for 4 weeks Continuous intake of test food B for 4 weeks Continuous intake of placebo food for 4 weeks CONDITION: healthy adult woman PRIMARY OUTCOME: 1.FSFI 2.Kupperman Women&#39;s Health Survey INCLUSION CRITERIA:

jRct (2021). "Double-blind sham-controlled trial of the urinary dysfunction treatment device O-NES in patients with refractory overactive bladder [Japan]." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Therapeutic intervention is carried out after baseline screening. The safety is confirmed after the end of therapeutic intervention. CONDITION: Overactive bladder PRIMARY OUTCOME: The change in the mean frequency of urinary incontinence episodes per day from the baseline in the treatment fourth week. SECONDARY OUTCOME: ‐The rate of change in the mean frequency of urinary incontinence episodes per day from the baseline.; ‐The mean daily urinary frequency and its change from the baseline.; ‐The rate of change in the mean daily urinary frequency from the baseline.; ‐The mean daily urinary urgency and its change from the baseline.; ‐The rate of change in the mean daily urinary urgency from the baseline.; ‐The change in the total Overactive Bladder Symptom Score (OABSS) from the baseline.; ‐The mean voided volume per micturition and its change from baseline.; ‐The maximum voided volume per micturition and its change from the baseline. INCLUSION CRITERIA: ‐They are aged 20 years or older at the time they give their informed consent. ‐They have been treated with anticholinergic drugs and beta3 receptor agonists in the past, but the symptoms of overactive bladder are persisting or they cannot use therapeutic drugs of overactive bladder due to certain reasons such as contraindications. ‐They have 2 points or higher of urinary urgency score (question 3) and 2 points or higher of urgency urinary incontinence score (question 4) in OABSS. ‐Their mean urinary incontinence with urinary urgency per day is 1 time or more and their mean urinary frequency per day is 8 times or more. ‐They have will and able to accurately record the urinary diary and complete the questionnaire throughout the trial period.

jRct (2022). "A dose determination study of NS-580 in patients with endometriosis (late phase II)." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Each participant will receive one of three oral doses (50 mg, 100 mg, 150 mg) of NS‐580 or placebo twice daily over a 24‐week intervention period. CONDITION: endometriosis PRIMARY OUTCOME: pelvic pain INCLUSION CRITERIA: ‐Patients who are clinically diagnosed with endometriosis ‐Patients whose severity of pelvic pain caused by endometriosis meets selection criteria ‐Patients with regular menstrual cycle ‐Patients aged 20 years or older and 49 years or younger (at the time of informed consent)

jRcts (2021). "Evaluation of the Effect of Reduced Coenzyme Q10 (CoQ10) for Reducing Acute Adverse Events During Radiotherapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Administeration of reduced CoQ10 or placebo during definitive radiotherpy for gynecologic tumors (cervical cancer, endometrial cancer, vaginal cancer) CONDITION: Cervical cancer,Endometrial cancer,Vaginal cancer ; Gynecologic tumor,Cervical cancer,Endometrial cancer,Vaginal cancer D002583,D016889,D014625 PRIMARY OUTCOME: Maximum number of increases from the number of normal defecation per day during radiotherapy SECONDARY OUTCOME: Effectiveness; Severity of diarrhea (CTCAE ver 5.0); Severity of abdominal pain (CTCAE ver 5.0); Whether or not to take antidiarrheal drugs; Days until the start of taking antidiarrheal drugs; QOL score (EORTC QLQ‐C30, QLQ‐CX24); Safety; All diseases observed during the protocol period INCLUSION CRITERIA: 1. Those who are pathologically diagnosed with any of the following gynecologic tumors. Cervical cancer Endometrial cancer Vaginal cancer 2. Those who are scheduled for any of the following treatments. Radiotherapy Postoperative radiotherapy 3. Women who are 20 years of age or older at the time of obtaining consent. 4. Those who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2 at the time of obtaining consent. 5. Those who can fill out the consent form about participation in this clinical research by themselves.

Juan Pablo, A., et al. (2021). "Updates on Conservative Management of Endometrial Cancer in Patients Younger than 45 years."
	
Juhász Margit, L. W., et al. (2021). "Vaginal Rejuvenation: A Retrospective Review of Lasers and Radiofrequency Devices." Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 47(4): 489-494.
	Background: Vaginal rejuvenation is a topic of interest to multiple specialties, including dermatologists, plastic and reconstructive surgeons, urologists, and gynecologists. Evidence suggests that minimally invasive, energy-based devices-radiofrequency and laser therapy-are effective at vaginal tightening and decreasing symptoms of genitourinary syndrome of menopause (GSM) and/or vulvovaginal atrophy (VVA).; Materials and Methods: A systematic review was completed using PubMed in November 2018 with search terms "vaginal" or "vagina" and "rejuvenation" or "tightening" or "laxity" or "radiofrequency" or "laser," as well as "genitourinary syndrome of menopause," "pelvic prolapse," "atrophic vaginitis," "vulvovaginal atrophy," "sexual function," "urinary incontinence," and "radiofrequency" or "laser." Inclusion criteria were articles written in English and clinical trials or case reports/series dealing with human subjects.; Results: We identified 59 studies (3,609 women) treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. Studies report improvement in symptoms of GSM/VVA and sexual function, high patient satisfaction, and minor adverse events, including treatment-associated pain, swelling, or vaginal discharge.; Conclusion: This review demonstrates radiofrequency and laser are efficacious for the treatment of vaginal laxity and/or atrophy. Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns. (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Júlia, Á., et al. (2022). "Investigating the safety and efficacy of female pelvic organ prolapse surgeries with versus without vaginal implants."
	
Julia, G., et al. (2021). "Effect of osteopathic manipulative treatment on the perception of pelvic pain - A systematic review with meta-analysis."
	
Juliana, C., et al. (2023). "Efficacy of pelvic floor rehabilitation techniques in the management of dyspareunia after uterine cervical neoplasms treatment: a systematic review and meta-analysis."
	
Juliana Vieira, Q., et al. (2024). "Surgical damage on women with Ovarian Endometrioma who underwent surgery: a systematic review and meta-analysis."
	
Jun Ji, H., et al. (2020). "Herbal Medicines (Danggui Liuhuang Decoctions) for Management of Menopausal Symptoms: A Systematic Review of Randomized Controlled Trials." Journal of Clinical Medicine 9(6).
	Danggui Liuhuang (DLH) decoctions are traditional herbal medicines that are widely used for menopausal symptoms. The objective of this systematic review was to investigate evidence of the efficacy of DLH decoctions for menopausal symptoms. Fifteen databases were searched from inception until 29 May, 2020. We included randomized controlled trials (RCTs) testing any type of DLH decoction. All RCTs investigating DLH decoctions or modified DLH decoctions were included. The methodological quality of the RCTs was evaluated using Cochrane's risk of bias assessment tool. We measured the certainty of evidence (CoE) according to the GRADE approach. A total of five RCTs met all of the inclusion criteria and were analyzed. The included RCTs had unclear risks of bias in most domains. Based on studies using the Kupperman index for the measurement of menopausal symptoms, DLH decoctions may have ameliorative effects on menopausal symptoms equivalent to those of conventional drug therapies, but we are very uncertain (MD 3.03, 95% CI -3.17 to 9.25, two studies, very low CoE). Compared with conventional drug therapies, DLH decoctions may reduce hot flashes (MD 0.17, 95% CI 0.28 to 0.06, three studies, low CoE). The difference in the response rate between treatments is very uncertain (risk ratio 1.1, 95% CI 1.07 to 1.25, three studies, very low CoE); the results may indicate that compared with drug therapy, DLH decoction therapy elicits responses in 84 more cases per 1000 cases. In conclusion, there is limited evidence that DLH decoctions improve menopausal symptoms equivalently compared with conventional drug therapies. However, the studies had unclear risks of bias, and the CoEs were very low in general. Additional large and rigorous studies are needed.

June, K., et al. (2021). "A systematic review of the effectiveness of non-pharmacologically derived skin care products for perimenopausal related eczema symptoms."
	
Jung Carrie, E., et al. (2022). "Impact of Vaginal Estrogen on the Urobiome in Postmenopausal Women With Recurrent Urinary Tract Infection." Female Pelvic Medicine & Reconstructive Surgery 28(1): 20-26.
	Objective: The aim of this study was to describe effects of vaginal estrogen (VE) on the urogenital microbiome in postmenopausal women with recurrent urinary tract infections (rUTIs).; Methods: This is a secondary analysis of 17 participants enrolled in a randomized controlled trial of VE versus placebo on urinary tract infection recurrence in postmenopausal women with rUTIs. Paired clean-catch urine samples were collected at baseline and after 6 months of VE and sequenced using 16S rRNA gene sequencing. Sequence reads were analyzed using Quantitative Insights Into Microbial Ecology 2. Changes in α diversity, β diversity, and differentially abundant genera were measured between paired baseline and 6-month samples and between those with a urinary tract infection at 6 months (failures) and those without (successes).; Results: Of the 17 women, 11 were successes and 6 were failures after 6 months of VE treatment. There was a significant change in α diversity from baseline to month 6 in samples overall (Kruskal-Wallis χ2 = 3.47, P = 0.037) and in the treatment success group (Yuen T = -2.53, P = 0.035). The increase in relative abundance of Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus iners AB-1 was correlated with month 6. A relative bloom of L. crispatus compared with L. gasseri was associated with treatment success (Kruskal-Wallis χ2 = 4.9, P = 0.0014).; Conclusions: Lactobacillus increases in the urogenital microbiome of postmenopausal women with rUTI after 6 months of VE. However, only the relative increase in L. crispatus specifically may be associated with treatment success.; Competing Interests: K.F. received grant/research support from Valencia Technologies. E.S.L. is a consultant in Axonics and received grant/research support from Boston Scientific, Cogentix/Uroplasty, and Pfizer, and UpToDate Royalties. The remaining others have declared they have no conflicts of interest. (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Jung, K. S., et al. (2021). "The Effects of Taping Combined with Wrist Stabilization Exercise on Pain, Disability, and Quality of Life in Postpartum Women with Wrist Pain: a Randomized Controlled Pilot Study." International Journal of Environmental Research and Public Health 18(7).
	The purpose of this study was to evaluate the effects of wrist stabilization exercise combined with taping on wrist pain, disability, and quality of life in postpartum women with wrist pain. Forty‐five patients with wrist pain were recruited and randomly divided into three groups: wrist stabilization exercise + taping therapy (WSE + TT) group (n = 15), wrist stabilization exercise (WSE) group (n = 15), and control group (n = 15). The WSE + TT and WSE groups performed wrist stabilization exercises for 40 min (once a day, five times a week for eight weeks), and the control group performed passive range of motion (P‐ROM) exercise for the same amount of time. Additionally, the WSE + TT group attached taping to the wrist and forearm during the training period. The visual analogue scale (VAS) was used to assess pain level of the wrist. The Disabilities of the Arm, Shoulder and Hand (DASH) and the Short Form‐36 (SF‐36) were used to evaluate the degree of wrist disability and quality of life, respectively. The WSE + TT group showed a significant decrease in wrist pain and functional disability compared to two groups (p < 0.05). Significant improvement in the SF‐36 score was observed in the WSE + TT and WSE groups compared to that in the control group (p < 0.05). However, there was no significant difference between the WSE + TT and WSE groups in the SF‐36. Our findings indicate that wrist stabilization exercise combined with taping is beneficial and effective in managing wrist pain and disability in postpartum women with wrist pain.

Jungmann, S., et al. (2023). "Impact of 3 months of detraining after high intensity exercise on menopause-related symptoms in early postmenopausal women - results of the randomized controlled actlife project." Frontiers in sports and active living 4: 1039754.
	Regular exercise might reduce postmenopausal symptoms, however even short-moderate periods of absence from exercise training might significantly reduce these positive effects. The aim of the study was thus to determine detraining effects on postmenopausal symptoms after a 3-month detraining period in early post-menopausal women. After 13 months, the exercise group (EG: n = 27; 54.6 ± 2.0; 23.6 ± 3.3 kg/m 2 ) had to abruptly stop their supervised, facility-based, high intensity aerobic and resistance group exercise conducted three times per week due to the COVID-19 pandemic and the corresponding lockdown of all training facilities in Germany. In parallel, the control group (CG: n = 27; 55.6 ± 1.6 years, 25.2 ± 5.2 kg/m 2 ) had to terminate their low-intensity exercise program performed once per week. Study endpoint as determined after 3 months of detraining was menopausal symptoms as determined by the Menopausal Rating Scale II (MRS II). The intention to treat principle with multiple imputation was applied. After 13 months of intense multicomponent exercise and significant exercise-induced effects on menopausal symptoms, a further 3 months of detraining resulted in non-significant deteriorations ( p = .106) in the exercise group, while non-significant improvements were observed in the control group ( p = .180). Corresponding group differences were significant ( p = .036) after detraining. Of importance, self-reported individual outdoor activities increased by about 40% in both groups during the three-month lock-down period. Three months of absence from a supervised high-intensity group exercise protocol resulted in detraining effects on postmenopausal symptoms even when outdoor physical activity was increased significantly.; Trial Registration Number: ClinicalTrials.gov: NCT03959995.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Jungmann, Hettchen, Kohl and Kemmler.)

Junuhiu, H., et al. (2023). "Is the solubility of nutrients beneficial to polycystic ovary syndrome metabolism? A Meta-analysis and Systematic Review." PROSPERO International prospective register of systematic reviews.
	
Jwa, S. C., et al. (2023). "Model-based estimation of the health care expenditure and out-of-pocket payment for assisted reproductive technology: A retrospective linkage study using the Japanese national ART registry." Journal of Obstetrics and Gynaecology Research 49(7): 1778-1786.
	Aim: From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system. Method(s): We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model. Result(s): We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%). Conclusion(s): Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations.Copyright © 2023 Japan Society of Obstetrics and Gynecology.

Kabukçu, C., et al. (2021). "Effect of ejaculatory abstinence period on sperm DNA fragmentation and pregnancy outcome of intrauterine insemination cycles: A prospective randomized study." Archives of Gynecology and Obstetrics 303(1): 269‐278.
	Purpose: To evaluate the effect of the ejaculatory abstinence period on sperm DNA fragmentation and pregnancy rates in IUI cycles. Methods: One hundred and twenty couples with unexplained infertility were prospectively randomized into two groups on the second day of their cycle. In group A, patients had 1‐day ejaculatory abstinence period; in group B patients had 3‐day ejaculatory abstinence period. Each patient was stimulated with gonadotropins, and IUI was performed. The primary outcome measure was clinical pregnancy and sperm DNA fragmentation rate. Results: The pregnancy rate was 17.3% and 18.5% in group A and group B, respectively. No significant difference was found among the groups (p = 0.803). The sperm DNA fragmentation rate for group A (20.71 ± 11.01) and group B (23.78 ± 12.64) were almost similar (p = 0.187). The sperm DNA fragmentation rate was 24.89 ± 12.89 in pregnant couples and 21.71 ± 11.69 in non‐pregnant couples (p = 0.288). Conclusion: Even after a short abstinence period of 1 day, compared to the standard abstinence period of 3 days, pregnancy rates are similar among unexplained infertility couples undergoing ovarian stimulation and IUI. ClinicalTrials: The study was registered at ClinicalTrials.gov with ID NCT04361292. Date of registration: 27 April 2020. The study was registered retrospectively.

Kacar, M. T., et al. (2022). "Letrozole as an adjunct treatment in antagonist cycles that previously failed in poor responders." Ginekologia polska 93(4): 267-272.
	OBJECTIVES: To investigate whether adding letrozole in the early follicular phase of a gonadotropin-releasing hormone (GnRH) antagonist (GA) stimulation cycle improves in vitro fertilization (IVF) outcomes in poor responder patients. MATERIAL AND METHODS: To be included in this study, patients had to have had at least one previous GA cycle and a subsequent GA cycle with added early follicular phase letrozole (LzGA). A total of 41 poor responder patients were identified based on the Bologna criteria. RESULT(S): The LzGA group had a lower dosage of follicular stimulating hormone (FSH) (p = 0.001), the duration of stimulation days (p = 0.015) and the duration of GnRH antagonist stimulation days (p = 0.033) when compared with controls. Comprehensive analysis of the cycle characteristics showed that the number of oocytes retrieved, the number of MII oocytes retrieved, the number of fertilized oocytes, and the fertilization rate were significantly higher in the LzGA cycle (p = 0.041, p = 0.019, p = 0.008, p = 0.01, respectively). The rate of cycle cancellation was lower in the LzGA group (24.4%) than in the GA group (48.8%), (p < 0.001). Although LzGA administration demonstrated a trend toward improved implantation and clinical pregnancy rates, this was an insignificant trend (p = 1.000, p = 0.177, respectively). CONCLUSION(S): Adjunctive letrozole administration seems to restore an IVF cycle by improving the cycle characteristics and reducing the total gonadotrophin dosage.

Kadhim, B. H., et al. (2021). "Comparison between the effect of atosiban and piroxicam administration before embryo transfer on in vitro fertilization outcome." Pharmacologyonline 1: 511‐516.
	Embryo implantation is the most critical step in assisted reproduction treatment and is influenced by multiple factors, including the age of the patient, embryo quality, and endometrial receptivity. Uterine contraction induced by the embryo transfer (ET) process may have an adverse effect on embryo implantation. To compare the effect atosiban and piroxicam administration at day of embryo transfer on implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate. The study included 60 patients diagnosed with primary or secondary infertility caused by a male or tubal‐related factor, mild endometriosis or unexplained factors. The patients were divided randomly into two groups. First group were administered bullous dose of atosiban (6.75 mg) intravenously 30 minutes before ET, the second group received piroxicam suppositories 20 mg 1‐2 hrs. before ET. Pregnancy outcome analyzed and compared between the two groups. Atosiban demonstrated higher pregnancy, implantation, live birth rates than piroxicam group (60 % versus 53.3 %), (37.8 % versus 23.9 %) and (94.4 % versus 81.25) respectively, and lower miscarriage rate compared to piroxicam (5.6 % versus18.75 %), however there was no significant differences between the two groups regarding the ICSI outcome with p value greater than 0.05.

Kaeser Carson, T., et al. (2022). "Bupivacaine Use After Posterior Colporrhaphy to Reduce Postoperative Pain: A Multicenter, Double-Blinded, Placebo-Controlled, Randomized Clinical Trial." Female Pelvic Medicine & Reconstructive Surgery 28(2): 72-76.
	Objective: The aim of this study was to determine if injection of bupivacaine into levator muscles after posterior colporrhaphy reduces postoperative pain.; Methods: This study was a multicenter, double-blinded, placebo-controlled, randomized clinical trial of 130 participants, comparing bilateral infiltration of puborectalis and iliococcygeus muscles with 0.5% bupivacaine without epinephrine or normal saline after vaginal prolapse repair that included a posterior colporrhaphy. Primary outcome was the 24-hour cumulative Visual Analog Scale (VAS) pain score (measured as a sum of VAS pain scores at postoperative hours 0, 4, 8, 16, and 24) across intervention allocations. Secondary outcomes include the individual VAS pain scores per postoperative times 0, 4, 8, 16, and 24 hours and at 1 and 2 weeks, morphine equivalent use, postoperative void trial success, and time to first bowel movement.; Results: Sixty-eight participants received bupivacaine, and 62 participants received normal saline. No significant differences were identified in the 24-hour postoperative cumulative VAS pain scores for the bupivacaine and normal saline arms, 19 and 18 (P = 0.71); individual pain scores per each postoperative assessment time; opiate use (24-hour use was 42 vs 48, P = 0.39; 48-hour use was 75 vs 37, P = 0.09); length of hospital stay (26 hours vs 22 hours, P = 0.069); hours to passing void trial (10 hours vs 12 hours, P = 0.17); or hours to first postoperative bowel movement (18 hours vs 12 hours, P = 0.78).; Conclusions: Use of bupivacaine for muscle block after posterior colporrhaphy does not reduce postoperative pain, opiate use, and time to first bowel movement, or increase void trial success.; Competing Interests: James L. Whiteside received money paid to him from the International Academy of Pelvic Surgery, and legal reviews. He received teaching honoraria from American Urogynecologic Society. All the other authors have declared that there are no conflicts of interest. (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Kagan, R., et al. (2024). "Pooled fezolinetant safety data over 52 weeks from three randomized Phase 3 studies (SKYLIGHT 1, 2 and 4)." Journal of Neurosurgical Anesthesiology 36(1): 1281.
	Objective: To present pooled safety data from three 52-week phase 3 fezolinetant studies (SKYLIGHT 1, 2 and 4; NCT04003155, NCT04003142, NCT04003389) in women with vasomotor symptoms (VMS; hot flashes and night sweats) associated with menopause. Design(s): SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies with the same design. Women aged >=40-<=65 y with moderate-to-severe VMS (minimum average >=7 hot flashes/day) were initially randomized to once-daily placebo, fezolinetant 30mg or 45mg (1:1:1). After 12 weeks, those on placebo were re-randomized to fezolinetant 30mg or 45mg, and those on fezolinetant continued on their assigned dose for 40 weeks. SKYLIGHT 4 was a placebo-controlled, double-blind, 52-week long-term safety study. Safety was assessed by frequency of treatment-emergent adverse events (TEAEs) and laboratory assessments including liver safety assessments. Result(s): A total of 952 participants in the placebo group; 1103 in the fezolinetant 30mg group and 1100 in the fezolinetant 45mg group took >=1 dose of study medication. Caffeine use was not restricted; 18% of each group were current smokers. Here we present safety data for fezolinetant 45mg (proposed dose for approval); results were consistent for 30mg. By group, TEAEs occurred in 55.3% of participants in the placebo and 62.9% in the fezolinetant 45mg group; exposure-adjusted results were consistent with these results (TABLE). The most frequent TEAEs (>5% in either group) were upper respiratory tract infections (8.2% placebo, 7.7% fezolinetant 45mg); headache (7.7% placebo, 8.2% fezolinetant 45mg); and COVID (4.1% placebo, 6.1% fezolinetant 45mg). There were 6 drug-related serious TEAEs (1 placebo, 5 fezolinetant 45mg). The incidence of elevations of hepatic transaminases was low, events were generally asymptomatic and resolved on treatment or on discontinuation. No Hy's Law cases were reported. A low incidence of bone fractures was reported, with similar incidences across groups. Endometrial hyperplasia or malignancy determined by the final biopsy diagnosis in fezolinetanttreated participants, assessed by centrally read endometrial biopsies, were within FDA pre-specified limits of <=1% with an upper limit of 1-sided 95% CI <=4%. There was no substantial difference in endometrial thickness measured by transvaginal ultrasonogram during the assessment period between fezolinetant- and placebo-treated participants. Conclusion(s): Pooled data affirm the safety and tolerability of fezolinetant over 52 weeks.

Kahleova, H., et al. (2023). "A dietary intervention for postmenopausal hot flashes: A potential role of gut microbiome. An exploratory analysis." Complementary Therapies in Medicine 79: 103002.
	Objective: This study examined the role of gut microbiome changes in mediating the effects of a dietary intervention on the frequency and severity of postmenopausal vasomotor symptoms METHODS: Postmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned, in 2 successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to stay on their usual diet. Over a 12-week period, frequency and severity of hot flashes were recorded with a mobile application. In a subset of 11 women, gut microbiome was analyzed at baseline and after 12 weeks of the dietary intervention (low-fat vegan diet with soybeans), using deep shotgun metagenomic sequencing. Differences in the microbiome between baseline and 12 weeks were assessed by comparing alpha diversity with Wilcoxon signed rank tests, beta diversity with permanovaFL, and taxon abundance with Wilcoxon signed rank tests. Pearson correlations were used to assess the association between changes in hot flashes and gut bacteria.; Results: In the subset for which microbiome testing was done, total hot flashes decreased by 95 % during the dietary intervention (p = 0.007); severe hot flashes disappeared (from 0.6 to 0.0/day; p = 0.06); and moderate-to-severe hot flashes decreased by 96 % (p = 0.01). Daytime and nighttime hot flashes were reduced by 96 % (p = 0.01) and 94 % (p = 0.004), respectively. Alpha and beta diversity did not significantly differ in the intervention group between baseline and 12 weeks. Two families (Enterobacteriaceae and Veillonellaceae), 5 genera (Erysipelatoclostridium, Fusicatenibacter, Holdemanella, Intestinimonas, and Porphyromonas), and 6 species (Clostridium asparagiforme, Clostridium innocuum, Bacteroides thetaiotaomicron, Fusicatenibacter saccharivorans, Intestinimonas butyriciproducens, Prevotella corporis, and Streptococcus sp.) were differentially abundant, but after correction for multiple comparisons, these differences were no longer significant. Changes in the relative abundance of Porphyromonas and Prevotella corporis were associated with the reduction in severe day hot flashes both unadjusted (r = 0.61; p = 0.047; and r = 0.69; p = 0.02), respectively), and after adjustment for changes in body mass index (r = 0.63; p = 0.049; and r = 0.73; p = 0.02), respectively). Changes in relative abundance of Clostridium asparagiforme were associated with the reduction in total severe hot flashes (r = 0.69; p = 0.019) and severe night hot flashes (r = 0.82; p = 0.002) and the latter association remained significant after adjustment for changes in body mass index (r = 0.75; p = 0.01).; Conclusions: This exploratory analysis revealed potential associations between changes in vasomotor symptoms in response to a diet change and changes in the gut microbiome. Larger randomized clinical trials are needed to investigate these findings.; Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest related to this manuscript. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Kahleova, H., et al. (2023). "Dietary advanced glycation end-products and postmenopausal hot flashes: A post-hoc analysis of a 12-week randomized clinical trial." Maturitas 172: 32-38.
	Objective: Postmenopausal hot flashes are associated with an increased risk of cardiovascular disease and diabetes. Because dietary advanced glycation end-products (AGEs) may act as endocrine disruptors, this study examined the potential association of modifications to the intake of dietary AGEs with the frequency and severity of postmenopausal hot flashes.; Methods: Postmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned to either the intervention group or the control group. The former were asked to follow a low-fat, vegan diet, including cooked soybeans (1/2 cup [86 g]/day) for 12 weeks, and the latter continued their usual diets for 12 weeks. Frequency and severity of hot flashes were recorded with a mobile application. Three-day diet records were analyzed using the Nutrition Data System for Research software and dietary AGEs were estimated, using a database. Seventy-one participants completed the whole study and 63 provided complete hot flash and dietary data for the AGEs analysis (n = 31 in the intervention and n = 24 in the control group). Pearson correlations were used to assess the association between changes in hot flashes and dietary AGEs.; Results: Dietary AGEs decreased in the intervention group by 73 %, that is by 5509 ku/day on average (95 % -7009 to -4009; p < 0.001), compared with the control group (+458; 95 % CI -835 to +1751; p = 0.47; treatment effect -5968 ku/day [95 % CI -7945 to -3991]; Gxt, p < 0.001). Severe hot flashes decreased by 92 % (p < 0.001) and moderate-to-severe hot flashes decreased by 88 % in the intervention group (p < 0.001). Changes in dietary AGEs correlated with changes in severe (r = +0.39; p = 0.002) and moderate hot flashes (r = +0.34; p = 0.009) and remained significant after adjustment for changes in energy intake (r = +0.45; p < 0.001; and r = +0.37; p = 0.004, respectively) and changes in body mass index (r = +0.37; p = 0.004; and r = +0.27; p = 0.04, respectively). The reduction in dietary AGEs required to achieve a predicted reduction in hot flashes by 1/day was 6933 ku/day for severe and 4366 ku/day for moderate-to-severe hot flashes.; Conclusions: The reduction in dietary AGEs with a low-fat plant-based diet was associated with a significant reduction in the frequency of severe and moderate-to-severe postmenopausal hot flashes, independent of changes in energy intake and weight loss. Plant-based diets could be used not only to alleviate vasomotor symptoms in postmenopausal women, but also to reduce other health risks associated with AGEs.; Trial Registration: ClinicalTrials.gov, NCT04587154.; Competing Interests: Declaration of competing interest Dr. Barnard is an Adjunct Professor of Medicine at the George Washington University School of Medicine. He serves without compensation as president of the Physicians Committee for Responsible Medicine and Barnard Medical Center in Washington, DC, nonprofit organizations providing educational, research, and medical services related to nutrition. He writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Kahleova, Ms. Holtz, Ms. Znayenko-Miller, Ms. Sutton, and Dr. Holubkov received compensation from the Physicians Committee for Responsible Medicine for their work on this study. Dr. Uribarri, Ms. Schmidt, Ms. Kolipaka, and Ms. Hata do not report any conflict of interest. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Kahn, B., et al. (2022). "Transvaginal Mesh Compared With Native Tissue Repair for Pelvic Organ Prolapse." Obstetrics and Gynecology 139(6): 975-985.
	Objective: To compare the safety and effectiveness of transvaginal mesh repair and native tissue repair, in response to a U.S. Food and Drug Administration (FDA) 522 study order to assess co-primary endpoints of superiority and noninferiority.; Methods: This was a prospective, nonrandomized, parallel cohort, multi-center trial comparing transvaginal mesh with native tissue repair for the treatment of pelvic organ prolapse. The primary endpoints were composite treatment success at 36 months comprised of anatomical success (defined as pelvic organ prolapse quantification [POP-Q] point Ba≤0 and/or C≤0), subjective success (vaginal bulging per the PFDI-20 [Pelvic Floor Distress Inventory]), and retreatment measures, as well as rates of serious device-related or serious procedure-related adverse events. Secondary endpoints included a composite outcome similar to the primary composite outcome but with anatomical success defined as POP-Q point Ba<0 and/or C<0, quality-of-life measures, mesh exposure and mesh- and procedure-related complications. Propensity score stratification was applied.; Results: Primary endpoint composite success at 36 months was 89.3% (201/225) for transvaginal mesh and 80.2% (389/485) for native tissue repair, demonstrating noninferiority at the preset margin of 12% (propensity score-adjusted treatment difference 6.5%, 90% CI -0.2% to 13.2%). Using the primary composite endpoint, transvaginal mesh was not superior to native tissue repair (P=.056). Using the secondary composite endpoint, superiority of transvaginal mesh over native tissue repair was noted (P=.009), with a propensity score-adjusted difference of 10.6% (90% CI 3.3-17.9%) in favor of transvaginal mesh. Subjective success for both the primary and secondary endpoint was 92.4% for transvaginal mesh, 92.8% for native tissue repair, a propensity score-adjusted difference of -4.3% (CI -12.3% to 3.8%). For the primary safety endpoint, 3.1% (7/225) of patients in the transvaginal mesh (TVM) group and 2.7% (13/485) of patients in the native tissue repair (NTR) group developed serious adverse events, demonstrating that transvaginal mesh was noninferior to native tissue repair (-0.4%, 90% CI -2.7% to 1.9%). Overall device-related and/or procedure-related adverse event rates were 35.1% (79/225) in the TVM group and 46.4% (225/485) in the NTR group (-15.7%, 95% CI -24.0% to -7.5%).; Conclusion: Transvaginal mesh repair for the treatment of anterior and/or apical vaginal prolapse was not superior to native tissue repair at 36 months. Subjective success, an important consideration from the patient-experience perspective, was high and not statistically different between groups. Transvaginal mesh repair was as safe as native tissue repair with respect to serious device-related and/or serious procedure-related adverse events.; Funding Source: This study was sponsored by Boston Scientific and developed in collaboration with FDA personnel from the Office of Surveillance and Biometrics, Division of Epidemiology.; Clinical Trial Registration: ClinicalTrials.gov, NCT01917968.; Competing Interests: Financial Disclosure Bruce S. Kahn disclosed receiving research support from Solaire, payments from AbbVie and Douchenay as a speaker, payments from Caldera and Cytuity (Boston Scientific) as a medical consultant, and payment from Johnson & Johnson as an expert witness. Lioudmila Lipetskaia disclosed that money was paid to their institution from Medtronic and Boston Scientific (both unrestricted educational grants for cadaveric lab). Karen Noblett is Chief Medical Officer at Axonics. Ayman Mahdy receives research funding from Axonics and is a consultant for Group Dynamics, Medpace and FirstThought. Ayman Mahdy was one of the PIs for the study few years ago and this entailed study support by the vendor. This support paid the study staff and patient recruitment process. Miles Murphy received research support and is a consultant for Boston Scientific, and is an expert witness for Johnson & Johnson. The other authors did not report any potential conflicts of interes . (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Kahn Ryan, M., et al. (2023). "Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination." Cancer immunology, immunotherapy : CII 72(1): 183-191.
	Background: To characterize the safety, immunogenicity, and outcomes of patients with high-grade serous ovarian cancer (HGSOC) in second or greater remission treated with a polyvalent antigen-KLH plus OPT-821 vaccine construct and bevacizumab.; Methods: Patients with recurrent HGSOC were treated with the vaccine plus bevacizumab at our institution from 01/05/2011 to 03/20/2012. Follow-up continued until 03/2021. Blood/urine samples were collected. "Responders" had an immunogenic response to ≥ 3 antigens; "non-responders" to ≤ 2 antigens.; Results: Twenty-one patients were treated on study. One developed a dose-limiting toxicity (grade 4 fever). Two (10%) experienced bevacizumab-related grade 3 hypertension. Thirteen (68%) and 16 (84%) of 19 responded to ≥ 3 and ≥ 2 antigens, respectively (Globo-H, GM2, TF cluster Tn, MUC-1). Four of 21 patients were alive > 5 years post-treatment. Responders and non-responders had a median PFS of 4.9 months (95% CI: 2.8-8.1) and 5.0 months (95% CI: 0.7-cannot estimate), respectively; median OS was 30.7 months (95% CI: 16.9-52.0) and 34.2 months (95% CI: 12.8-cannot estimate), respectively. On two-timepoint analysis (baseline, week 17), increased IL-8 exhibited improved PFS (HR as 10-unit increase, 0.43; p = 0.04); increased PDGF exhibited worse OS (HR as 10-unit increase, 1.01; p = 0.02).; Conclusions: This is the longest follow-up of vaccine administration with bevacizumab in patients with ovarian cancer. The vaccine was well tolerated with bevacizumab. Response was not associated with improved survival. On two-timepoint analysis, increased IL-8 was associated with significant improvement in PFS; increased PDGF with significantly worse OS. For all timepoint measurements, cytokine levels were not significantly associated with survival.; Trial Registration: NCT01223235. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kahyaoglu, I., et al. (2023). "Early or late response in poor responders: does it make a difference in cycle outcome?" Human Fertility 26(6): 1485-1490.
	Ovarian response to stimulation mainly determines the length of stimulation. However, there is no clarity in the literature regarding the optimal duration required to achieve oocyte maturity in patients with the poor ovarian response (POR) defined by Bologna criteria. Therefore, a total of 267 cycles that fulfilled the inclusion criteria were selected retrospectively. Group A constitute of patients with a stimulation period < 9 d (n = 70); and group B included patients with a stimulation period >= 9 d (n = 133). The results showed that antral follicle count (5.72 +/- 1.82 vs. 5.10 +/- 1.78, p = 0.023), serum oestradiol level on hCG day (1286.88 +/- 778.18 pg/mL vs. 820.14 +/- 479.04 pg/mL, p = 0.001), and total gonadotropin dose used (2949.53 +/- 727.92 IU vs 2020.94 +/- 415.17 IU, p = 0.0001) were higher in group B when compared to group A. Although the number of total (5.47 +/- 3.32 vs 3.86 +/- 2.15, p = 0.0001) and mature oocytes retrieved (4.34 +/- 2.88 vs 2.84 +/- 1.67, p = 0.0001) were higher in group B, no significant difference was observed in the pregnancy rates between groups (25.6 vs 15.7%, p > 0.05). In conclusion, no deleterious effect of a shorter duration of stimulation on cycle outcome was seen in patients with POR.Copyright © 2023 The British Fertility Society.

Kailasam, A. and C. Langstraat (2022). "Contemporary Use of Hormonal Therapy in Endometrial Cancer: a Literature Review." Current treatment options in oncology 23(12): 1818-1828.
	Opinion Statement: Most endometrial cancers are estrogen receptor and progesterone receptor positive. Hormonal therapy in endometrial cancer is best used in patients with low-grade disease and hormone receptor positivity. Though not standard of care, hormonal treatment can be considered in endometrial cancer treatment in both the early-stage upfront setting for patients who are not surgical candidates and in advanced and recurrent endometrial cancer. In patients who desire fertility preservation or who are not surgical candidates, levonorgestrel intrauterine device and oral progesterone are preferred treatment options. In patients with advanced and metastatic disease, there is no standard-of-care second-line treatment, and hormonal treatment is a widely accepted option for low-grade disease. Beyond progesterone, selective estrogen receptor modulators, aromatase inhibitors, gonadotropin-releasing hormone agonists, and fulvestrant are hormonal treatment options. New therapies, such as MTOR inhibitors and CDK 4/6 inhibitors, have been extensively studied in breast cancer and are shown to be useful in conjunction with hormonal therapies particularly when there is suspected resistance to anti-estrogen treatment. Hormonal therapies also tend to be better tolerated than chemotherapy agents, making them a desirable option particularly in patients with lower performance status. Results from ongoing clinical trials will hopefully help shed light on the use of combination treatment in patients with hormone receptor-positive, low-grade metastatic, and recurrent endometrial cancer. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Kakar Sham, S., et al. (2024). Combination Therapy for Recurrent Ovarian Cancer.
	No Results Available Drug: DOXIL|Drug: Withaferin A|Drug: Ashwagandha|Drug: Combination of ASWD and DOXIL Progression-free survival (PFS)|Incidence of adverse events (AE)|Objective response rate (ORR)|Duration of response|Overall survival Female Phase 1|Phase 2 72 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 22.0392 November 2027

Kakargia, E., et al. (2023). "The role of maternal physical activity on in vitro fertilization outcomes: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 307(6): 1667-1676.
	Purpose: This systematic review is designed to summarize the evidence concerning the impact of maternal physical activity on the reproductive outcomes following assisted reproduction techniques (ART), namely in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).; Methods: We searched for eligible studies on PubMed, EMBASE databases and the Cochrane Library from their inception until September 2021. Our primary outcomes were live birth rate and miscarriage, while secondary ones included clinical pregnancy and implantation rates. The quality of the evidence was evaluated using a study-specific adaptation of the Robins I tool.; Results: Quantitative data from 10 cohort studies (CS) and 2 randomized control trials (RCT), involving 3431 women undergoing ART treatments, were included in the analyses. The pooled results exhibited uncertainty regarding the effect of physical activity on live birth rate per woman (OR 1.15, 95% CI 0.92-1.43, p = 0.23, I 2 = 61%, 9 studies) and miscarriage rates (OR 0.79, 95% CI 0.44-1.43, p = 0.43, I 2 = 44%, 6 studies). However, physical activity was associated with significantly improved clinical pregnancy rate after ART (OR 1.39, 95% CI 1.08-1.79, p = 0.0009, I 2 = 68%, 10 studies), whereas implantation rate after ART almost reached statistical significance (OR = 1.95, 95% CI 0.99-3.82, p = 0.05, I 2 = 77%).; Conclusion: The current evidence is still insufficient to firmly conclude on the effect of maternal physical activity on live birth, miscarriage and implantation rates. Although clinical pregnancy rates favored physical activity in this group of patients, these results must be undertaken with caution due to the low quality and the high heterogeneity of the studies included. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kalaitzopoulos Dimitrios, R., et al. (2023). "Treatment after endometrioma recurrence: a narrative review." Minerva Obstetrics and Gynecology 75(5): 449-459.
	Introduction: Ovarian endometrioma is a common subtype of endometriosis with a prevalence between 17 and 44%. The reported average recurrence of endometrioma after surgical management is 21.5% after 2 years and 40-50% after 5 years. The aim of this narrative review was to summarize the existing literature focusing on treatment options after endometrioma recurrence in order to provide an evidence-based approach for the clinical practice.; Evidence Acquisition: Three electronic databases (MEDLINE, EMBASE and Cochrane) were searched until September 2022 for eligible studies.; Evidence Synthesis: The available studies showed that repeated surgery has a negative impact on ovarian function, without improving the fertility outcomes. Transvaginal aspiration as an alternative option for surgery has a high rate of recurrence, which varies from 8.20 to 43.5% depending on the technique used and on the study population. Pregnancy related outcomes were similar between transvaginal aspiration groups and no intervention groups in patients with endometrioma recurrence. Regarding medical treatments, only four studies were found, showing that progestins reduce the pain and the diameter of the ovarian cyst.; Conclusions: Recurrent endometrioma is a challenging condition which could be encountered during the care of women with endometriosis. The decision about the treatment-strategy has to be individualized considering family planning status, age, ovarian reserve and transvaginal ultrasound findings. Well-designed randomized clinical trials are needed to export safer conclusions about the most appropriate treatment in each specific condition after endometrioma recurrence.

Kalampokis, N., et al. (2022). "Re: aina Salazar, Lucas Regis, Jacques Planas, et al. A Randomised Controlled Trial to Assess the Benefit of Posterior Rhabdosphincter Reconstruction in Early Urinary Continence Recovery after Robot-assisted Radical Prostatectomy. Eur Urol Oncol 2022;5: 460-3." European urology oncology 5(4): 472‐473.
	
Kale, A., et al. (2022). "Comparison of Isolated Sciatic Nerve and Sacral Nerve Root Endometriosis: A Review of the Literature." Journal of Minimally Invasive Gynecology 29(8): 943-951.
	Objective: This review aimed to compare isolated sciatic and sacral nerve root endometriosis in terms of anatomic distribution, patients' symptoms and history, diagnostics, treatments, and outcomes.; Data Source: We searched PubMed, MEDLINE, Web of Science, and Embase from inception to October 2021 using a combination of keywords including "sciatic nerve endometriosis," "sacral nerve root endometriosis," and associated Medical Subject Headings. Relevant publications and references were also checked for further articles.; Methods of Study Selection: Two independent researchers performed the study selection. We included all original research articles, case reports, and case series in English that reported on the isolated sciatic nerve and sacral nerve root endometriosis.; Tabulation, Integration, and Results: The initial search identified 92 articles, and 40 articles, mostly case reports and case series, were included. The review included 362 patients: with 256 and 106 patients in the sacral and the sciatic groups, respectively. In both groups, most patients had right-sided endometriosis. In the sciatic group, most of the patients presented with foot drop, leg motor weakness, and sciatic dermatome hypoesthesia. The frequencies of all these symptoms were significantly higher in the sciatic group (all p <.001). By contrast, in the sacral group, most of patients presented with pudendal neuralgia (p <.001). Intraoperative, early, late, and 1-year postoperative complications did not differ significantly between the 2 groups.; Conclusion: This study indicated that isolated sciatic and sacral nerve root endometrioses were more common on the right side. Laparoscopic surgery was more commonly performed over traditional open or transgluteal surgery techniques. Sacral nerve root endometriosis is often accompanied by deep infiltrating endometriosis. Magnetic resonance imaging and myelography may be useful diagnostic tools in the preoperative workup. There was usually no significant improvement after surgery in cases of isolated sciatic nerve endometriosis presenting with foot drop. (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Kale, A. R., et al. (2021). "A Comparative, Randomized Control Trial in Patients of Per Vaginal Bleeding Comparing Efficacy of Oral Dydrogesterone Versus Vaginal Progesterone in Successful Pregnancy Outcome for Patients with Recurrent Pregnancy Loss." Journal of obstetrics and gynaecology of India 71(6): 591-595.
	BACKGROUND: Progesterone is essential for the maintenance of a healthy pregnancy. Any defect in the secretion of human chorionic gonadotropin or progesterone is associated with a significantly increased risk of first-trimester abortion. Progesterone is frequently prescribed to patients presenting with per vaginal (PV) bleeding in early pregnancy and a history of recurrent pregnancy loss. METHODS: Pregnant women up to 12 weeks of gestation with a history of more than two early pregnancy losses and presenting with vaginal bleeding were included in this study. All subjects were randomized to receive either vaginal progesterone 600 mg/day or oral dydrogesterone 30 mg/day. A detailed history-including menstrual history, previous pregnancies, previous miscarriages, and other risk factors-was obtained. The mean time required for the cessation of PV bleeding and continuation of pregnancy up to 24 weeks and till term was compared. RESULTS: A total of 200 patients were randomized to vaginal progesterone 600 mg/day (n = 100) or oral dydrogesterone 30 mg/day (n = 100). While 74 patients had two miscarriages in the progesterone group, 68 patients had two miscarriages in the dydrogesterone group. The time required for complete cessation of bleeding was significantly lesser among patients who received oral dydrogesterone compared to those who received intravaginal progesterone (53.90 ± 9.09 vs. 94.60 ± 7.29 h, p < 0.0001). Numerically higher number of patients receiving oral dydrogesterone had a successful continuation of pregnancy up to 24 weeks of gestation, as well as till full term compared to progesterone group (70 vs. 75). CONCLUSION: Oral dydrogesterone is preferred over vaginal progesterone in patients presenting with vaginal bleeding during early pregnancy and a history of recurrent early pregnancy loss.

Kali, Z. and F. T. Cagiran (2022). "Surgical removal of intramural fibroids improves the TNF-α induced inflammatory events in endometrium." European Review for Medical and Pharmacological Sciences 26(24): 9180-9186.
	Objective: To investigate whether surgical removal of intramural fibroids makes any changes in the expression of endometrial tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NF-κB).; Patients and Methods: 20 patients who had no pathology other than intramural fibroid as a cause of subfertility were included in the study. 6 patients who planned tubal ligation were considered as the control group. Type 3 or 4 fibroid diagnosis was made according to the revised International Federation of Gynecology and Obstetrics (FIGO). At the end of the diagnostic and confirmatory tests, 8 patients were diagnosed with type 3 and 12 patients with type 4 fibroids. While the patients in the fibroid group went to myomectomy, the patients in the control group went to tubal ligation. Before the myomectomy, endometrial sampling was performed with a pipelle cannula under anesthesia. The same procedure was repeated three months after the treatment. The same endometrial sampling procedure was also performed on the patients in the control group. TNF-alpha and NF-κB levels were measured with enzyme-linked immunosorbent assay (ELISA) in endometrial samples taken before and three months after myomectomy.; Results: Pre-myomectomy TNF-α levels of the patients in the type 3 fibroid group were significantly higher than the control group (5.10±1.30 vs. 2.50±0.11, p<0.01). Similarly, the pre-myomectomy TNF-α levels of the patients in the type 4 fibroid group were significantly higher than the control group (4.73±1.76 vs. 2.50±0.11, p<0.01). There was no significant difference between pre-myomectomy endometrial TNF-α levels of patients in type 3 and 4 fibroid groups (5.10±1.30 vs. 4.73±1.76, p>0.05). Removal of type 3 fibroids by myomectomy significantly decreased TNF-α levels (5.10±1.30 vs. 2.20±0.44, p<0.03). Similarly, removal of type 4 fibroids by myomectomy significantly decreased TNF-α levels (4.73±1.76 vs. 2.60±0.30, p<0.04). Pre-myomectomy NF-κB levels of the patients in the type 3 fibroid group were significantly higher than the control group (2.42±0.39 vs. 1.09±0.60, p<0.02). Similarly, the pre-myomectomy NF-κB levels of the patients in the type 4 fibroid group were significantly higher than the control group (2.04±0.50 vs. 1.09±0.60, p<0.01). There was no significant difference between the pre-myomectomy endometrial NF-κB levels of the patients in the type 3 and 4 fibroid groups (2.42±0.39 vs. 2.04±0.50 p>0.05). Removal of type 3 fibroids by myomectomy significantly decreased NF-κB levels (2.42±0.39 vs. 1.02±0.33, p<0.01). Similarly, removal of type 4 fibroids by myomectomy significantly decreased NF-κB levels (2.04±0.50 vs. 0.97±0.02, p<0.02).; Conclusions: Surgical removal of type 3 or type 4 fibroids contributes positively to receptivity by down-regulating endometrial TNF-α and NF-ƙB.

Kali, Z. and F. T. Cagiran (2023). "The effect of endometrioma cystectomy on dysmenorrhea and noncyclic pelvic pain: VAS and endometrioma cystectomy." Annals of Clinical and Analytical Medicine 14(7): 586-589.
	Aim: In this study, we aimed to evaluate the effect of endometrioma cystectomy on dysmenorrhea and noncyclic pelvic pain with a linear visual analog scale (VAS). Material(s) and Method(s): Sixteen patients who were admitted with the diagnosis of symptomatic endometrioma and planned for endometrioma cystectomy were included in the study. Ten patients for whom cystectomy was decided due to non-endometriotic benign ovarian cysts were included in the control group. Pre- and postoperative VAS scores were recorded in the control group. Before the operation and in the first and third months of the postoperative period, patients with dysmenorrhea and noncyclic pelvic pain were asked to mark the perceived pain intensity on a 100 mm horizontal line. The area they marked was measured from the left edge with a ruler divided into 1 mm units and VAS scores were recorded. Result(s): VAS values recorded to determine the severity of dysmenorrhea before endometrioma cystectomy decreased significantly in the first and third-month scorings after cystectomy. Similarly, VAS values recorded to evaluate noncyclic pelvic pain intensity before cystectomy decreased significantly in the first and third postoperative months. A more significant decrease was found in the VAS values recorded in the third month for both dysmenorrhea and noncyclic pelvic pain compared to the first month. Uni- or bilateral endometrioma did not significantly affect the decrease in VAS values. There were non-significant decreases in preoperative and postoperative VAS scores of the patients in the control group. There was no significant difference between the mean pain reductions for dysmenorrhea and noncyclic pelvic pain. Discussion(s): Endometrioma cystectomy leads to a significant decrease in dysmenorrhea and noncyclic pelvic pain VAS scores. The decrease in VAS values becomes more evident as the postoperative period is prolonged.Copyright © 2023, Derman Medical Publishing. All rights reserved.

Kalleas, D., et al. (2022). "Live birth rate following undisturbed embryo culture at low oxygen in a time-lapse incubator compared to a high-quality benchtop incubator." Human fertility (Cambridge, England) 25(1): 147-153.
	Time-lapse (TL) incubators are increasingly used in in vitro fertilization (IVF) laboratories but there have been few studies of their effectiveness in comparison to other incubator types. Moreover, the design of most studies has been limited by the quality of the control incubator. We have therefore performed a one-year pseudo-randomized prospective study of IVF cycles using a TL incubator (EmbryoScope™) ( n = 243) or a conventional incubator (K-System G-185 Flatbed) ( n = 203). The two groups were well matched in terms of clinical parameters: IVF cycle attempt number, IVF/ICSI, age, number and day (3 or 5) of embryo transfer. Embryos were selected for transfer using conventional (non-TL) morphological grading. The EmbryoScope group had an increased chance of a live birth (43.2% vs. 34.5%; OR = 1.43 [95%CI: 0.96-2.13]) with significantly reduced early pregnancy loss (5.8% vs. 13.8%; OR = 0.37 [0.19-0.74]) compared to the K-System incubator. There was a higher proportion of 4-cell embryos on day 2 and 8-cell embryos on day 3 in the EmbryoScope, compared to the K-Systems. The use of TL incubators is appropriate in ART by virtue of their high specification, facility for low oxygen culture and provision of minimally disturbed culture conditions which limit exposure of human embryos to environmental stress.

Kalogera, E., et al. (2019). "Enhanced Recovery Following Minimally Invasive Gynecologic Procedures with Bowel Surgery: A Systematic Review." Journal of Minimally Invasive Gynecology 26(2): 288-298.
	Enhanced Recovery After Surgery (ERAS) is an evidence-based approach to perioperative care of the surgical patient. A mounting body of literature in gynecologic surgery has demonstrated that ERAS improves postoperative outcomes, shortens hospital length of stay and reduces cost without increasing complications or readmissions. Most of the existing literature has concentrated on open surgery, questioning if patients undergoing minimally invasive surgery (MIS) also derive benefit. Our aim was to systematically review the literature on ERAS following minimally invasive gynecologic surgery (MIGS) with and without bowel surgery. Given the paucity of studies on ERAS in MIGS with bowel surgery (one study), we expanded our search to include studies of ERAS in patients undergoing minimally invasive colorectal resections alone. Twelve studies were identified through an electronic database search of PubMed, MEDLINE, and Ovid EMBASE. These studies included patients undergoing MIGS for benign and/or malignant indications and showed that ERAS pathways decreased length of stay and/or increased the proportion of same-day discharge surgeries, improved patient satisfaction, and reduced hospital costs while maintaining low postoperative complication and readmission rates. Although limited, data from a single study suggests that ERAS in MIGS with bowel surgery leads to shortened hospital stay, stable postoperative morbidity and readmissions. While the variation between the published protocols underscores the need for standardization, existing literature supports the adoption of ERAS as safe and effective when planning MIGS.

Kaltenecker, B., et al. (2022). "Vaginal Cancer." StatPearls.
	Primary vaginal cancer is rare, making up 1% to 2% of all female reproductive tract cancers. The vagina is a unique organ with distinct tissue types and planes. It is a 7 to 10-cm-long fibromuscular tube extending from the cervix to the vulva. It sits posterior to the urethra and bladder and anterior to the rectum. The organ is divided into three parts, which are important for classifying tumor location and lymphatic drainage. The lower third is below the level of the bladder base with the urethra anteriorly. The middle third is adjacent to the bladder base, and the upper third is at the level of the vaginal fornices. The vaginal fornices are denoted as anterior, posterior, and lateral to the cervix. Primary vaginal cancer is strictly defined as a disease without evidence of cervical or vulvar cancer or a history of these diseases within five years. Most vaginal lesions (approximately 80% to 90%) will originate from cervical or vulvar lesions or from other local sites such as the endometrium, bladder, rectosigmoid, or ovary. Although they can also metastasize from distant sites such as the colon, breast, and pancreas. Once there is a suspicion of primary vaginal cancer, a biopsy should confirm this histologically. While current estimates of vaginal cancer maybe are higher than vulval malignancy, these estimates include primary and other genital lesions. Currently, there are no randomized trials for the treatment of vaginal cancers due to the rarity of the disease. Guidelines are generally based on limited studies. (Copyright © 2022, StatPearls Publishing LLC.)

Kaltsouni, E., et al. (2022). "Grey matter morphology in women with premenstrual dysphoric disorder treated with a selective progesterone receptor modulator." European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 65: 35-43.
	Premenstrual dysphoric disorder (PMDD) is characterized by severe cyclic mood symptoms emerging in the luteal phase of the menstrual cycle. The variation in progesterone levels and its metabolites during the luteal phase seems critical to the occurrence of PMDD symptoms. Notably, the efficacy of selective progesterone receptor modulator (SPRM) treatment on the mental symptoms of PMDD has been recently demonstrated. In the present study, structural magnetic resonance imaging was used to assess the effects of SPRM treatment, compared with placebo, on grey matter morphology in women with PMDD. In total, 35 women were scanned during the luteal phase, before and after three months of treatment with SPRM or placebo. Symptom severity was assessed using the Daily Record of Severity of Problems (DRSP), while gonadal hormone levels were measured by liquid chromatography-tandem mass spectrometry. Region-of-interest and whole-brain approaches were employed to perform voxel-based morphometry analyses, subcortical volumetric analyses, and surface-based morphometry analyses. No interaction or main effects of treatment and time were observed on grey matter volume and cortical surface measures (cortical thickness, gyrification index, sulcal depth, and fractal dimension). The relationship between change in brain morphology and symptom severity was also explored but no treatment-dependant grey matter structure change was related to symptom severity change. These findings suggest that SPRM treatment does not impart macrostructural changes onto grey matter structure, at least in the short term.; Competing Interests: Conflict of Interest RL received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. ISP has served occasionally on advisory boards or acted as invited speaker at scientific meetings for Asarina Pharma, Bayer Health Care, Gedeon Richter, Peptonics, Shire/Takeda, Sandoz, and Lundbeck A/S. All other authors declare that they have no conflict of interest. (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Kamal, N., et al. (2022). "Traditional Medicinal Uses, Phytochemistry, Biological Properties, and Health Applications of Vitex sp." Plants (Basel, Switzerland) 11(15).
	The genus Vitex is also known as a chaste tree, in which it is a large shrub native to the tropical and subtropical regions of the world. A diverse range of species is distributed throughout Southern Europe, the Mediterranean, and Central Asia. The Vitex tree, including its leaves and fruits, has been used for herbal remedies in the form of pastes, decoctions, and dried fruits since ancient times. This article aimed to prepare a comprehensive review of traditional uses and secondary metabolites derived from Vitex sp., including the chemical compounds, biological activities, application of Vitex in human clinical trials, toxicology and safety, marketed products, and patents. The scientific findings were obtained using a number of search engines and databases, including Google Scholar, PMC, and ScienceDirect. Vitex species are well known in pharmacology to have medicinal values, such as anti-inflammatory, antibacterial, antifungal, antimicrobial, antioxidant, and anticancer properties. Previous studies reported that some species are proven to be effective in treating diseases, such as diabetes, and improving female health. A total of 161 compounds from different Vitex species are reported, covering the literature from 1982 to 2022. A chemical analysis report of various studies identified that Vitex exhibited a wide range of phytoconstituents, such as iridoid, diterpenoid, ecdysteroid, and flavonoid and phenolic compounds. Apart from that, the review will also discuss the application of Vitex in human clinical trials, toxicology and safety, marketed products, and patents of the genus. While the extracts of the genus have been made into many commercial products, including supplements and essential oils, most of them are made to be used by women to improve menstrual conditions and relieve premenstrual syndrome. Among the species, Vitex agnus-castus L. is the only one that has been reported to undergo clinical trials, mainly related to the use of the genus for the treatment of mastalgia, menstrual bleeding problems, amenorrhea, menorrhagia, luteal insufficiency, and premenstrual syndrome. Overall, the review addresses recent therapeutic breakthroughs and identifies research gaps that should be explored for prospective research work.

Kamarudin, M., et al. (2021). "Is hyacinth exercise better than pelvic floor exercise alone for urinary incontinence: a randomized trial." Urogynaecologia 33(1).
	Urinary Incontinence (UI) negatively impact women’s physical, psychological and health‐related quality of life. Pelvic strengthening exercise is the first line management in UI. We hypothesized that Hyacinth exercise is better than Pelvic Floor Exercise (PFE) in strengthening pelvic floor muscles, thus reducing female urinary incontinence. This randomized controlled trial involved 180 women with UI. Participants were taught on either Hyacinth exercise or PFE alone. Improvement in urinary symptoms and pelvic muscle strength were evaluated using a validated female pelvic floor questionnaire and objectively measured at 2 months and 6 months. Significant improvement in urinary symptoms and pelvic muscle strength post treatment at 2 months and 6 months was seen in both groups with p≤0.001. Although earlier improvement seen in Hyacinth group, it did not reach level of significant when compared, between the two exercises. Mean bladder score (PFE vs Hyacinth arm) 9.13±6.54 vs. 8.74±5.21, p=0.93 (2 months) and 5.80±4.15 vs. 5.79±4.22, p=0.92 (6 months). Although there was no statistical difference between the two groups for our primary and secondary outcomes, Hyacinth group demonstrated earlier improvement in urinary symptoms at 2 months.

Kamenov, Z., et al. (2023). "Comparing the Efficacy of Myo-Inositol Plus alpha-Lactalbumin vs. Myo-Inositol Alone on Reproductive and Metabolic Disturbances of Polycystic Ovary Syndrome." Metabolites 13(6): 717.
	Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein alpha-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus alpha-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and alpha-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus alpha-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus alpha-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus alpha-lactalbumin. The benefits of associating myo-inositol and alpha-lactalbumin clearly make this combination a true edge in the management of PCOS.Copyright © 2023 by the authors.

Kamenov, Z., et al. (2023). "Comparing the Efficacy of Myo-Inositol Plus α-Lactalbumin vs. Myo-Inositol Alone on Reproductive and Metabolic Disturbances of Polycystic Ovary Syndrome." Metabolites 13(6).
	Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.

Kameo, Y., et al. (2024). "Effects of non-face-to-face gait and muscle strength training for urinary incontinence in community-dwelling middle-aged and older women: A randomized controlled trial." [Nihon koshu eisei zasshi] Japanese journal of public health 71(1): 15-23.
	ObjectivesAlthough the effectiveness of status-to-interview-guided exercise therapy to improve urinary incontinence has been reported, reports on non-face-to-face guided exercise therapy are lacking. This study aimed to analyze the effect of using non-face-to-face training guidance for walking and strength training on the frequency and degree of urinary incontinence and improvement in the urinary incontinence-induced decline in the quality of life (QoL) of community-dwelling middle-aged and older women.MethodsThis study included 68 women, aged 46-64 years, having self-evaluated stress urinary incontinence. The participants in the intervention group watched a video that guided them on how to walk effectively and gradually increase their number of steps. Additionally, a non-face-to-face lecture was conducted on the comprehensive training content, including muscle strengthening exercises necessary for walking at home, as muscle weakness is one of the causes of urinary incontinence. The control group was instructed to continue living as usual without any interventions. The intervention period was 12 weeks. The primary endpoints included the urinary leakage frequency score, urinary leakage volume score, and degree of decline in the QoL, and these were compared before and after the intervention using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). To elucidate the effect of the increase in the step count on the primary outcome, we calculated the rate of increase in the step count before and after the intervention in the intervention group. Moreover, a sub-analysis was performed for the high-step count (n=16) and low step-count (n=16) groups before and after the intervention.ResultsSignificant differences were observed in the urinary leakage frequency, urinary leakage volume, and ICIQ-SF scores at 12 weeks post-intervention between the groups (P<0.05). In the high-step count group, both the urinary leakage frequency and ICIQ-SF scores showed a significant tendency to improve from 8 weeks compared to the pre-intervention scores.ConclusionSince this study was conducted as an open-label trial, the possibility of an inherent bias in subjective outcome assessment should be considered during interpretation of the results. Our findings indicate that walking and muscle strength training, even with non-face-to-face guidance, for middle-aged and older community-dwelling women with urinary incontinence can effectively improve the urinary leakage symptoms and degree of decline in the QoL. Furthermore, greater effects could be expected by encouraging an increase in the number of daily steps with the intervention.

Kamińska, W., et al. (2023). "Lifestyle intervention towards Mediterranean Diet, physical activity adherence and anthropometric parameters in normal weight women with Polycystic Ovary Syndrome or Hashimoto's Thyroiditis - preliminary study." Annals of agricultural and environmental medicine : AAEM 30(1): 111-117.
	Introduction: Overweight and obesity are frequently present in both women with polycystic ovary syndrome (PCOS) and with Hashimoto's thyroiditis (HT). This is a limited study regarding the benefits of lifestyle changes, including dietary habits, dedicated to patients with HT and PCOS.; Objective: The aim of the study was to assess the effectiveness of an intervention programme based on the Mediterranean Diet (MD) without caloric restriction and increased physical activity to change selected anthropometric parameters in women with both health conditions.; Material and Methods: The intervention programme consisted of changing the participants diet towards MD rules and increasing physical activity for 10 weeks according WHO recommendation. The study involved 14 women diagnosed with HT, 15 with PCOS and 24 women from a control group. The intervention programme consisted of educating patients in the form of a lecture, dietary advice, leaflets and a 7-day menu based on MD. During the programme, patients were required to implement recommended lifestyle changes. The mean intervention time was 72 ± 20 days. Nutritional status was analyzed by body composition, degree of implementation of the principles of the MD by using the MedDiet Score Tool, and the level of physical activity by the IPAQ-PL questionnaire. The above-mentioned parameters were evaluated twice, before and after the intervention.; Results: The intervention programme consisting in implementing the principles of the MD and increasing physical activity to effect a change in the anthropometric parameters of all groups of women studied; all women had a reduction in body fat and body mass index. A decrease in waist circumference was observed in the group of patients with Hashimoto's disease.; Conclusions: An intervention programme based on the Mediterranean Diet and physical activity can be a good way to improve the health of HT and PCOS patients.

Kaminski, J., et al. (2021). "Effects of oral versus transdermal estradiol plus micronized progesterone on thyroid hormones, hepatic proteins, lipids, and quality of life in menopausal women with hypothyroidism: a clinical trial." Menopause (New York, N.Y.) 28(9): 1044-1052.
	OBJECTIVE: The aim of the study was to evaluate the effects of usual doses of oral estradiol with transdermal estradiol and the effects of these estrogens plus micronized progesterone (MP) in menopausal women with primary hypothyroidism. METHODS: Twenty women were randomized to 12 weeks of treatment with estradiol 1 mg tablets or estradiol 1 mg gel. Then, women with a uterus received a 100 mg capsule of oral MP. Thyroid function, thyroxine-binding globulin (TBG), sex hormone-binding globulin (SHBG), insulin-like growth factor 1 (IGF-1), lipid profiles, and quality of life were measured at baseline and after 12 and 24 weeks. RESULTS: Oral estradiol led to an increase in total T4 levels (5.84 ± 1.11 vs 8.41 ± 1.61 μg/dL; P < 0.001); changes in thyroid-stimulating hormone (TSH) levels were clinically important in 3 of 10 participants who needed to increase their dose of levothyroxine. Significant changes were detected in hepatic proteins with oral estradiol: TBG and SHBG levels increased (15.29 ± 3.87 vs 20.84 ± 5.49 μg/mL, P < 0.001; 61.85 ± 33.6 vs 121.4 ± 49.36 nmol/L, P < 0.001; respectively), whereas IGF-1 levels decreased (152 ± 38.91 vs 96 ± 17.59 ng/mL; P < 0.001). Transdermal estradiol alone did not significantly affect the thyroid function. Transdermal estradiol plus MP led to a decrease in TSH levels (1.79 ± 1.05 vs 1.09 ± 0.52 mIU/L; P = 0.04), while total T4 levels increased (7.54 ± 1.34 vs 9.95 ± 2.24 μg/dL; P = 0.01). Hormonal therapy had a greater impact on depressed mood and vasomotor symptoms. CONCLUSIONS: Total T4 and TBG levels increase after oral estradiol in women with hypothyroidism and it may cause clinical changes in TSH levels. Conversely, transdermal estradiol alone or plus MP does not cause major changes in thyroid function in these women.

Kamp, E., et al. (2022). "Menopause, skin and common dermatoses. Part 1: hair disorders." Clinical and experimental dermatology 47(12): 2110-2116.
	Menopause, which usually occurs between the age of 45 and 55 years, is associated with falling oestrogen levels due to ovarian follicle depletion. The impact on the cardiovascular system and bone density are well documented; however, further research required to establish the impact on the skin and hair. In this first part of a four-part review, we examine the effect of menopause on the hair. We performed a literature review on dermatology and hair in menopause. Androgens and oestrogens are involved with regulation of the hair cycle, with a reduction in anagen hairs seen in postmenopausal women. Female pattern hair loss and frontal fibrosing alopecia have both been associated with the perimenopausal and postmenopausal states. It is clear that menopause and the change in hormone levels have an impact on the hair cycle and common hair conditions. However, further research is required, particularly to understand the therapeutic targets and role of hormonal therapy. (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Kampers, J., et al. (2022). "Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy." Archives of Gynecology and Obstetrics 306(2): 295-314.
	Purpose: Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery.; Methods: Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time.; Results: 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI - 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference - 114.34 [- 122.97; - 105.71]) and RH (mean difference - 287.14 [- 392.99; - 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference - 3.06 [- 3.28; - 2.83]) and RH (mean difference - 3.77 [- 5.10; - 2.44]) compared to AH.; Conclusion: Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials. (© 2021. The Author(s).)

Kampers, J., et al. (2021). "Protective operative techniques in radical hysterectomy in early cervical carcinoma and their influence on disease-free and overall survival: a systematic review and meta-analysis of risk groups." Archives of Gynecology and Obstetrics 304(3): 577-587.
	Purpose: Radical hysterectomy with pelvic lymphadenectomy presents the standard treatment for early cervical cancer. Recently, studies have shown a superior oncological outcome for open versus minimal invasive surgery, however, the reasons remain to be speculated. This meta-analysis evaluates the outcomes of robotic and laparoscopic hysterectomy compared to open hysterectomy. Risk groups including the use of uterine manipulators or colpotomy were created.; Methods: Ovid-Medline and Embase databases were systematically searched in June 2020. No limitation in date of publication or country was made. Subgroup analyses were performed regarding the surgical approach and the endpoints OS and DFS.; Results: 30 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Patients were analyzed concerning the surgical approach [open surgery (AH), laparoscopic surgery (LH), robotic surgery (RH)]. Additionally, three subgroups were created from the LH group: the LH high-risk group (manipulator), intermediate-risk group (no manipulator, intracorporal colpotomy) and LH low-risk group (no manipulator, vaginal colpotomy). Regarding OS, the meta-analysis showed inferiority of LH in total over AH (0.97 [0.96; 0.98]). The OS was significantly higher in LH low risk (0.96 [0.94; 0.98) compared to LH intermediate risk (0.93 [0.91; 0.94]). OS rates were comparable in AH and LH Low-risk group. DFS was higher in the AH group compared to the LH group in general (0.92 [95%-CI 0.88; 0.95] vs. 0.87 [0.82; 0.91]), whereas the application of protective measures (no uterine manipulator in combination with vaginal colpotomy) was associated with increased DFS in laparoscopy (0.91 [0.91; 0.95]).; Conclusion: DFS and OS in laparoscopy appear to be depending on surgical technique. Protective operating techniques in laparoscopy result in improved minimal invasive survival. (© 2021. The Author(s).)

Kamphuis, D., et al. (2023). "Correction: the effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial." BMC Women's Health 23(1): 424.
	
Kamphuis, D., et al. (2023). "The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial." BMC Women's Health 23(1): 233.
	Background: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. Method(s): This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. Discussion(s): The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. Trial registration number: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).Copyright © 2023, The Author(s).

Kamphuis, D., et al. (2023). "Does tubal flushing by hysterosalpingo-foam sonography and hysterosalpingography affect tubal patency? Results from a randomized clinical trial." Human Reproduction 38(Supplement 1): i117-i118.
	Study question: Does tubal flushing by hysterosalpingo-foam-sonography (HyFoSy) or hysterosalpingography (HSG) affect tubal patency in infertile women? Summary answer: Tubal flushing by HyFoSy and HSG does not increase the number of women with visible bilateral tubal patency. What is known already: HyFoSy and HSG are two frequently used methods to visualize tubal patency by flushing a contrast fluid through the Fallopian tubes, while the uterus and Fallopian tubes are imaged using respectively fluoroscopy and ultrasound. Tubal flushing by HSG, specifically with oil-based contrast, improves live birth rates in infertile women. The mechanism of this fertility-enhancing effect is still not completely understood. The potential fertility-enhancing effect of other tubal flushing methods, for example HyFoSy, are studied less frequently. Here, we investigated whether tubal flushing affect tubal patency, and therefore could explain the fertility-enhancing effect of tubal flushing. Study design, size, duration: This is a secondary analysis of the FOAMtrial, a multi-center RCT in which women were assigned to undergo tubal flushing by HSG and HyFoSy in randomized order. They either had HyFoSy first and then HSG or the other way around. Here, we assess whether tubal flushing by either HSG or HyFoSy led to differences in tubal patency. We also investigate whether the type of contrast used during HSG (oil-and water based) influenced tubal patency. Participants/materials, setting, methods: We studied infertile women with indication for tubal patency testing. Women with anovulatory cycles, endometriosis or with a partner with male infertility were excluded. The main outcome was the number of women with bilateral tubal patency. This outcome, was compared in two analyses: 1) Tubal flushing by HyFoSy versus no flushing, with HSG as reference test, and 2) Tubal flushing by HSG (with oil - or water contrast) versus no flushing, with HyFoSy as reference test. Main results and the role of chance: Between May 2015 and January 2019, 1,160 women were included. There were 957 women who underwent HyFoSy with interpretable results and 1,081 women who underwent HSG with interpretable results. Tubal flushing by HyFoSy versus no tubal flushing, with HSG done in all women as reference test, evaluating the effect of tubal flushing by HyFoSy, resulted in a comparable number of women with visible bilateral tubal patency: 467/537 (87%) vs. 472/544 (87%) ; (RR 1.00; 95%CI: 0.96-1.05). Tubal flushing by HSG (with both water -and oil-based contrast) versus no tubal flushing, with HyFoSy done in all women as reference test, evaluating the effect of tubal flushing by HSG, did not show an increase of women with visible bilateral tubal patency: 394/471 (84%) vs. 428/486 (88%); RR 0.95; (95%CI:0.90-1.00). Tubal flushing by HSG with oil-based contrast versus no flushing, with HyFoSy as reference test, resulted in a comparable number of women with visible bilateral tubal patency: 283/330 (86%) vs. 271/308 (88%); RR 0.97; (95%CI:0.92-1.04). Tubal flushing by HSG with water-based contrast versus no flushing, with HyFoSy as reference test, did show a decrease of women with visible bilateral tubal patency: 108/137 (79%) vs. 156/171 (91%); RR 0.90 (95%CI:0.83-0.98). Limitations, reasons for caution: It needs to be noted that subtle improvements of tubal patency, caused by initial tubal flushing with either HyFoSy or HSG, cannot be detected on respectively ultrasound and fluoroscopy images and were therefore not assessed in this study. Wider implications of the findings: The therapeutic effect of tubal flushing cannot be explained by dissolving visible obstruction in the Fallopian tubes. This suggests that the therapeutic effect of tubal flushing mainly applies to women with anatomically normal Fallopian tubes.

Kanadys, W., et al. (2020). "Effects of red clover (Trifolium pratense) isoflavones on the lipid profile of perimenopausal and postmenopausal women-A systematic review and meta-analysis." Maturitas 132: 7-16.
	Aim: The aim of this systematic review and meta-analysis was to clarify the effect of a specific standardised extract of red clover (Trifolium pratense) on the lipid profile of perimenopausal and postmenopausal women.; Methods: Medline (PubMed), EMBASE, and Cochrane Library electronic databases were searched for papers in English reporting randomized controlled trials published up to 2017. Reference lists from those papers were checked for further relevant publications. Studies were identified and reviewed for their eligibility for inclusion in this review. The changes from baseline in the levels of individual components of the lipid profiles were used to assess differences between the active treatment and placebo groups. Weighted mean differences and 95 % confidence intervals were calculated for continuous data using a random-effects model.; Results: Ten eligible studies (twelve comparisons) with 910 peri- and postmenopausal women were selected for systematic review. The meta-analysis showed changes in serum levels: total cholesterol, -0.29 (95 % CI: -0.53 to -0.06) mmol/L [-11.21 (95 % CI: -20.49 to -13.92) mg/dL], p = 0.0136; LDL-cholesterol, -0.13 (95 % CI: -0.35 to 0.09) mmol/L [-5.02 (95 % CI: -13.53 to 3.48) mg/dL], p = 0.2418; triglycerides, -0.15 (95 % CI: -0.32 to 0.01) mmol/L [-13.28 (95 % CI: -28.34 to 0.88) mg/dL], p = 0.0592; and HDL-cholesterol, 0.14 (95 % CI: -0.08 to 0.36) mmol/L [5.41 (95 % CI: -3.09-13.92) mg/dL], p = 0.2103. TheI 2 statistic ranged from 87.95%-98.30 %, indicating significant heterogeneity.; Conclusions: The results suggest that a red clover extract is efficacious in reducing the concentrations of total cholesterol; however, changes in HDL-C, LDL-C and triglycerides are not as pronounced. Potentially, this means that women takingTrifolium pratense for menopausal symptoms can derive additional benefits from the plant's specific effect that corrects abnormal cholesterol levels. Additional studies are needed to assess its effects on post-menopausal women. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Kancheva, L., et al. (2021). "Short report: cognitive behavioral therapy - a primary mode for premenstrual syndrome management: systematic literature review." Psychology, health & medicine 26(10): 1282-1293.
	Most women in reproductive age experience at least one premenstrual syndrome (PMS) symptom every month over many years, and about 5% experience significant impairment, requiring professional intervention. Offering effective and sustainable treatment, is essential. While research acknowledges the effectiveness of nonpharmacological methods, cognitive behavioral therapy (CBT) and lifestyle modifications, as a treatment alternative, selective serotonin reuptake inhibitors or hormonal ovulation suppression continue to be recommended as a first-line treatment. We hypothesize that nonpharmacological methods will be sufficient for effective and sustainable PMS management. A systematic literature review was conducted for peer-reviewed original studies with the search terms: CBT, psychoeducation, PMS and premenstrual dysphoric disorder. All 32 identified studies found a significant reduction in PMS to complete remission with nonpharmacological interventions. No side effects were reported, and positive effect was sustained over time. Psychoeducational self-help packages, delivered with the affordance of modern technology, appeared to be enough for most women to manage successfully their PMS distress. Most severe PMS forms required one-to-one CBT. Nonpharmacological methods can be recommended as the primary mode for PMS management. More high-quality research is required, for developing personalized self-help packages, as well as the full use of modern technology for delivering the service.

Kanchibhotla, D., et al. (2023). "Management of dysmenorrhea through yoga: A narrative review." Frontiers in pain research (Lausanne, Switzerland) 4: 1107669.
	Menstrual pain also known as dysmenorrhea is one of the most common and underrated gynecological disorders affecting menstruating women. Although the symptoms and impact might vary greatly, it is defined by cramps in the lower abdomen and pain that radiates to lower back and thighs. In some cases it is also accompanied by nausea, loose stool, dizziness etc. A primary narrative review was conducted on the impact of yoga on dysmenorrhea experienced by women. The English-language literature published until 2022 was searched across databases such as PubMed, Google Scholar and Scopus. "Yoga" and "menstrual pain" OR "dysmenorrhea" were used as keywords for the search across several databases. A total of 816 title searches were obtained across all the database searches. This review article included 10 studies based on the selection criteria. The studies examined the impact of a varied set of 39 asanas, 5 pranayamas and Yoga nidra on dysmenorrhea. The studies demonstrated a significant relief in dysmenorrhea among those who practiced Yoga (asanas/pranayama/yoga nidra) with improved pain tolerance and reduced stress levels. Regulating the stress pathways through yoga was found to be a key in regulating hormonal balance and reduction in dysmenorrhea.

Kanda, S., et al. (2023). "Effect of Metformin (MTF) Intervention During Pregnancy in Women With Polycystic Ovarian Syndrome (PCOS): A Systematic Review." Cureus 15(8): e44166.
	Metformin (MTF) is a commonly prescribed medication for women with polycystic ovarian syndrome (PCOS), but its impact on pregnancy outcomes in women with PCOS remains controversial. This systematic review aims to evaluate the effects of MTF intervention on pregnancy outcomes in women with PCOS and the impact of MTF on offspring. A comprehensive search is conducted in PubMed, Google Scholar, and ScienceDirect databases from 2019 up to May 16, 2023. Only review articles and meta-analyses are included, focusing on women with PCOS who received MTF during pregnancy or as part of infertility treatment. The primary outcomes of interest are clinical pregnancy rate (CPR), miscarriage rate, preterm birth rate, and live birth rate. Secondary outcomes are the safety profile of MTF. Data extraction and quality assessment are performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the assessment using the multiple systematic reviews (AMSTAR) 2 tool, respectively. The initial search produced 1877 studies. Thirteen studies were included in the review. While the use of MTF during pregnancy in women with PCOS may have some benefits in reducing certain pregnancy complications such as pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), preeclampsia, preterm delivery, reducing the risk of ovarian hyperstimulation syndrome (OHSS) in women with PCOS undergoing in vitro fertilization (IVF); however, there is no significant difference in clinical pregnancy and live birth rates overall, but subgroup analysis suggests potential benefits for women with a higher body mass index (BMI). MTF is associated with a larger fetal head circumference and potential long-term effects on offspring's BMI and obesity. Further research is needed to better understand the optimal dosing of MTF, long-term effects, and effects in specific subgroups. The heterogeneity of the included studies limited the ability to analyze the data effectively, leading to challenges in drawing definitive conclusions.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Kanda et al.)

Kandru, M., et al. (2023). "Effects of Conventional Exercises on Lower Back Pain and/or Pelvic Girdle Pain in Pregnancy: A Systematic Review and Meta-Analysis." Cureus 15(7): e42010.
	Pregnant women frequently complain of low back discomfort associated with their pregnancies. On their quality of life, it could have a detrimental effect. Pregnancy-related low back pain (LBP) and pelvic girdle pain (PGP) are associated with substantial direct and indirect expenditures. Evidence addressing strategies to treat and prevent these illnesses needs to be clarified. This review aimed to examine the connection between exercise, LBP, and PGP. To find relevant studies (in the English language) that matched the inclusion and exclusion criteria, a systematic search of peer-reviewed literature was carried out using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, Scopus, the Web of Science, Pub Med, and ClinicalTrials.Gov. The publishing window was limited to the previous 10 years (2012-2022). Utilizing Review Manager version 5.4 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen), the results were examined. JADAD ratings were used to evaluate the quality of the included studies. To analyze the endpoints, the mean, standard mean difference (SMD), and 95% confidence intervals (CI) were determined. We chose 16 randomized controlled trials (RCTs) that included 1885 pregnant individuals with pelvic girdle and/or lower back discomfort. The combined data showed that the exercise group had lower VAS scores than the control group. The final result, however, did not significantly differ. Most of the studies had high JADAD scores, ranging from 3 to 5 points. Lower back pain and/or pelvic girdle discomfort during pregnancy are not influenced by exercise; however, women who are provided with a regular exercise program appear to manage the condition effectively with improved functional status.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Kandru et al.)

Kaneda, C., et al. (2020). "Physical Activity and Body Mass Index in Relation to Infertility in Women." Reviews on recent clinical trials 15(3): 199-204.
	BACKGROUND: Infertility is a global social issue, and reproductive health is a priority in global health. This review aimed to study the relation between physical activity (PA) and infertility in non-obese or non-overweight women. METHODS: We used search strategies in the National Library of Medicine database including the PubMed database to October 2019 to find articles related to women and fertility, infertility, exercise, PA, pregnancy rate, live births, fecundability, and conception. Only cohort studies or randomized controlled trials in English were chosen for review that included outcomes directly related to becoming pregnant. We selected studies in which the participants were categorized by low or high body mass index (BMI). RESULTS: We found 6 papers meeting our criteria. In the association between PA and outcome, vigorous PA in women with low BMI resulted in both positive and negative effects that were weaker than those in women with high BMI. Among women with low BMI, moderate PA was weakly but positively associated with outcome whereas walking was not. CONCLUSION: We observed some trends and slight difference between outcomes of women with low versus high BMI. There are only a few studies on infertile women with low BMI, and further investigation is warranted.

Kang, G., et al. (2021). "The efficacy of pilates on urinary incontinence in Korean women: a metabolomics approach." Metabolites 11(2): 1‐18.
	Pilates has been known as exercise intervention that improves the function of pelvic floor muscle (PFM) associated with impacting urinary incontinence (UI). This study investigated the effect of Pilates on UI in Korean women by determining the change in functional movement of PFM (FMP) and metabolic profiles. UI group with Pilates (UIP, n = 13) participated in 8‐weeks Oov Pilates program, and 8 subjects were assigned to Control and UI group with no Pilates (UINP), respectively. Before and after 8 weeks, plasma samples were collected from all participants, and ultrasonography was used to measure the functional change of PFM for calculating FMP ratio. Plasma samples were analyzed by mass spectrometry to identify the change of metabolic features. After 8‐weeks intervention, FMP ratio was remarkably decreased in UIP (48.1% ↓, p < 0.001), but not in Control and UINP (p > 0.05). In metabolic features, L‐Glutamine (m/z: 147.07 [M + H]+), L‐Cystathionine (m/z: 240.09 [M + NH4 ]+), L‐Arginine (m/z: 197.1 [M + Na]+), and L‐1‐Pyrroline‐3‐hydroxy‐5‐carboxylate (m/z: 147.07 [M + NH4 ]+) were significantly elevated solely in UIP (p < 0.001). Our study elucidated that Pilates can ameliorate the FMP and enhance the specific metabolic characteristics, which was potentially associated with invigorated PFM contractility to effectively control the bladder base and continence.

Kang Harmeet, K., et al. (2020). "PROTOCOL: Effectiveness of interpersonal psychotherapy in comparison to other psychological and pharmacological interventions for reducing depressive symptoms in women diagnosed with postpartum depression in low and middle-income countries: A systematic review." Campbell systematic reviews 16(1): e1074.
	Postpartum Depression (PPD) is highly prevalent among women in low and middle income countries (LMICs). World Heath Organization has recognised interpersonal Psychotherapy (IPT) as the first line treatment for the postpartum depression. The primary aim of this review is to evaluate the effectiveness of IPT alone or in combination with pharmacotherapy or other psychosocial therapies for treating depressive symptoms in women with postpartum depression. The generated evidence from this review will help to inform policies in relation to the treatment of postpartum depression in LMICs. (© 2020 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Kang, O.-J., et al. (2023). "Laparo-endoscopic single-site versus conventional laparoscopic surgery for early-stage endometrial cancer: A randomized controlled non-inferiority trial." Gynecologic Oncology 173: 74-80.
	Objective: To evaluate the feasibility and safety of laparo-endoscopic single-site surgery (LESS) compared with conventional laparoscopic surgery (CLS) for early-stage endometrial cancer.; Methods: Patients with clinical stage IA, IB, grade 1-3 endometrial cancer were randomly assigned to undergo LESS or CLS. The primary endpoint was the non-inferiority of LESS to CLS in terms of operation time and the number of resected pelvic lymph nodes. We set the non-inferior margin of the operation time as within 15% (24 min) and the number of resected pelvic lymph nodes as within 20% (5.2 lymph nodes).; Results: There was no significant difference between the LESS group (n = 53) and the CLS group (n = 54) in terms of age, weight, body mass index, parity, menopausal status, history of abdominal surgery, and preoperative CA-125 levels. The total operation time was comparable between the two groups. On average, 4.6 fewer pelvic lymph nodes were retrieved in the LESS group, which was within the non-inferiority margin. There were no significant differences in the incidence of intra- and postoperative complications, estimated blood loss, and postoperative hospital stay between the two groups. After a median follow-up time of 34 months (range, 2-242), the progression-free survival rates were 96.2% and 98.1% (P = 0.55) in the LESS group and the CLS group, and the overall survival rates were 98.1% and 100.0% (P = 0.31), respectively.; Conclusion: LESS surgical staging was non-inferior to CLS and had acceptable feasibility, safety, and efficacy for the surgical management of early-stage endometrial cancer.; Trial Registration: Clinicaltrial.gov identifier number: NCT01679522.; Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Kang, Y., et al. (2021). "The Efficacy and Safety of Extracorporeal Shockwave Therapy versus Acupuncture in the Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Evidence Based on a Network Meta-analysis." American journal of men's health 15(6): 15579883211057998.
	The aim of this study was to evaluate the efficacy and safety of extracorporeal shockwave therapy (ESWT) and acupuncture therapy for patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).We searched electronic databases including PubMed, Cochrane Library, Embase and web of science from its inception to June 1, 2021. The randomized controlled trials (RCTs) that compared ESWT and acupuncture in the management of CP/CPPS were identified. A network meta-analysis was conducted with the software of STATA 14.0.Nine RCTs with 525 patients were enrolled in our analysis. The results revealed that both ESWT and acupuncture were significantly better than the sham procedure in the outcomes of total score of NIH-CPSI, pain subscore, urinary symptoms subscore, QoL subscore, IPSS score, the IIEF score and response rates ( p < .05). Both ESWT and acupuncture were well-tolerated and had no obviously increased adverse events. Compared with acupuncture, ESWT was associated with better short term (<4w) and mid-term (8-12 w) efficacy of total score, pain subscore, urinary symptoms subscore, and QoL subscore of NIH-CPSI, IPSS score, IIEF score, and response rate. However, ESWT did not present better long-term (<24 w) outcomes than acupuncture in total score, pain subscore, urinary symptoms subscore, and QoL subscore of NIH-CPSI.Both ESWT and acupuncture were effective and well-tolerated in the management of CP/CPPS. ESWT seemed to have better short (<4 w) and mid-term (8-12 w) efficacy but similar long-term (>24 w) efficacy than acupuncture.

Kannan, P. and U. M. Bello (2023). "Efficacy of various forms of acupuncture for the treatment of urinary incontinence in women: A systematic review and meta-analysis." Explore 19(1): 26-35.
	Background and purpose: Evidence regarding the efficacy of various forms of acupuncture for the treatment of urinary incontinence (UI) in women is outdated and inconclusive. This review aims to determine the efficacy of different forms of acupuncture for the treatment of UI in women. Method(s): Multiple databases were searched from inception to June 2020. Randomized controlled trials that compared various forms of acupuncture to control were included. Result(s): Ten trials were included in this review. The pooled analysis demonstrated that an increased proportion of women with stress UI (SUI) reported fewer UI episodes (1.73 [95% CI 1.46, 2.04]; p < 0.00001) in the electroacupuncture group than in the sham group. The meta-analysis also revealed a significantly increased number of women who reported the complete cure of SUI in the electroacupuncture combined with pelvic floor muscle training group than in the medication group (RR 2.67 [95% CI 1.51, 4.71]; p = 0.0007). Body and laser acupuncture caused significant decreases in the number of urge accidents (-2.70 [95% CI -4.86, -0.54]; p = 0.01) and the occurrence of urgency symptoms (-3.60[95% CI -5.34, -1.86]; p < 0.0001), compared with sham acupuncture. Conclusion(s): Based on the findings of this review, electroacupuncture may be able to improve SUI in women in clinical settings. This review also identified evidence supporting the use of body, electro,- and laser acupuncture for the treatment of urge UI; however, these results were obtained from single studies, and further research remains necessary to confirm the effects of these interventions on the treatment of urge UI in women.Copyright © 2022

Kannan, P., et al. (2019). "Ankle positions potentially facilitating greater maximal contraction of pelvic floor muscles: a systematic review and meta-analysis." Disability and Rehabilitation 41(21): 2483-2491.
	Objectives: To evaluate the effect of ankle positions on pelvic floor muscles in women. Method(s): Multiple databases were searched from inception-July 2017. Study quality was rated using the grading of recommendations, assessment, development, and evaluation system and the "threats to validity tool". Result(s): Four studies were eligible for inclusion. Meta-analysis revealed significantly greater resting activity of pelvic floor muscles in neutral ankle position (-1.36 (95% CI -2.30, -0.42) p=0.004) and induced 15degree dorsiflexion (-1.65 (95% CI -2.49, -0.81) p=0.0001) compared to induced 15degree plantar flexion. Significantly greater maximal voluntary contraction of pelvic floor was found in dorsiflexion compared to plantar flexion (-2.28 (95% CI -3.96, -0.60) p=0.008). Meta-analyses revealed no significant differences between the neutral ankle position and 15degree dorsiflexion for either resting activity (0.30 (95% CI -0.75, 1.35) p=0.57) or maximal voluntary contraction (0.97 (95% CI -0.77, 2.72) p=0.27). Conclusion(s): Pelvic floor muscle-training for women with urinary incontinence could be performed in standing with ankles in a neutral position or dorsiflexion to facilitate greater maximal pelvic floor muscle contraction. As urethral support requires resting contraction of pelvic floor muscles, decreased resting activity in plantar flexion identified in the meta-analysis indicates that high-heel wearers with urinary incontinence might potentially experience more leakage during exertion in a standing position. Implications for rehabilitation Pooled analyses revealed that maximal voluntary contraction of pelvic floor muscle is greater in induced ankle dorsiflexion than induced plantar flexion. As pelvic floor muscle strengthening involves achieving a greater maximal voluntary contraction, pelvic floor muscle training for women with stress urinary incontinence could be performed in standing either with ankles in a neutral position or dorsiflexion. Decreased resting activity in plantar flexion identified in the meta-analysis indicates that high-heel wearers with stress urinary incontinence might potentially experience more leakage during exertion in a standing position. Women with stress urinary incontinence should be advised to wear flat shoes instead of high-heels and should be cautioned about body posture and ankle positions assumed during exercise and daily activities.

Kansal, Y., et al. (2024). "Impact of Surgical Modality on Endometrial Cancer Treatment: A Pragmatic Single-Center Analysis." Journal of Gynecologic Surgery.
	Objectives: Single-center prospective comparative analysis of case selection and surgical outcomes in patients with endometrial cancer, using three surgical modalities. Method(s): A total of 119 patients with endometrial cancer were recruited consecutively and, most of them were allotted to the robotic surgery and laparoscopic surgery cohorts. A few patients whose cancers were considered unfit for minimally invasive surgery underwent open surgery. Result(s): There were 119 patients in the study: 37 had robotic staging; 64 had laparoscopic staging; and 18 had open (laparotomic) surgical staging. The mean operative times were similar among the robotic, laparoscopic, and open-surgery groups (172.43 minutes versus 169.45 minutes versus 166.67 minutes, p = 0.927). The open-surgery cohort had a higher mean blood loss (217.22 mL versus 195.00 mL versus 123.91 mL; p = 0.041), similar blood transfusion rates (22.2% versus 10.8% versus 9.4%; p = 0.320), longer mean hospital stays (4.76 days versus 3.09 days versus 2.89 days; p = 0.000), and a higher rate of postoperative complications (55.6% versus 22.2%, versus 18.7%; p = 0.006), compared with the robotic and laparoscopic cohorts, all respectively. There was no significant difference in the rate of major complications and the number of lymph nodes retrieved among the groups (p = 0.424). Conclusion(s): Minimally invasive surgical techniques are safe and feasible for endometrial cancer, with superior outcomes to open surgery in terms of perioperative morbidity. The choice for robotic or laparoscopic modalities can be made, depending upon availability, surgeon preference, and the cost factor involved in robotic surgery.Copyright © Mary Ann Liebert, Inc.

Kanter, J., et al. (2023). "Hormonal stimulation reduces numbers and impairs function of human uterine natural killer cells during implantation." Human reproduction (Oxford, England) 38(6): 1047-1059.
	Study Question: How does an altered maternal hormonal environment, such as that seen during superovulation with gonadotropins in ART, impact human uterine immune cell distribution and function during the window of implantation?; Summary Answer: Hormonal stimulation with gonadotropins alters abundance of maternal immune cells including uterine natural killer (uNK) cells and reduces uNK cell ability to promote extravillous trophoblast (EVT) invasion.; What Is Known Already: An altered maternal hormonal environment, seen following ART, can lead to increased risk for adverse perinatal outcomes associated with disordered placentation. Maternal immune cells play an essential role in invasion of EVTs, a process required for proper establishment of the placenta, and adverse perinatal outcomes have been associated with altered immune cell populations. How ART impacts maternal immune cells and whether this can in turn affect implantation and placentation in humans remain unknown.; Study Design, Size, Duration: A prospective cohort study was carried out between 2018 and 2021 on 51 subjects: 20 from natural cycles 8 days after LH surge; and 31 from stimulated IVF cycles 7 days after egg retrieval.; Participants/materials, Setting, Methods: Endometrial biopsies and peripheral blood samples were collected during the window of implantation in subjects with regular menstrual cycles or undergoing superovulation. Serum estradiol and progesterone levels were measured by chemiluminescent competitive immunoassay. Immune cell populations in blood and endometrium were analyzed using flow cytometry. uNK cells were purified using fluorescence-activated cell sorting and were subjected to RNA sequencing (RNA-seq). Functional changes in uNK cells due to hormonal stimulation were evaluated using the implantation-on-a-chip (IOC) device, a novel bioengineered platform using human primary cells that mimics early processes that occur during pregnancy in a physiologically relevant manner. Unpaired t-tests, one-way ANOVA, and pairwise multiple comparison tests were used to statistically evaluate differences.; Main Results and the Role of Chance: Baseline characteristics were comparable for both groups. As expected, serum estradiol levels on the day of biopsy were significantly higher in stimulated (superovulated) patients (P = 0.0005). In the setting of superovulation, we found an endometrium-specific reduction in the density of bulk CD56+ uNK cells (P < 0.05), as well as in the uNK3 subpopulation (P = 0.025) specifically (CD103+ NK cells). In stimulated samples, we also found that the proportion of endometrial B cells was increased (P < 0.0001). Our findings were specific to the endometrium and not seen in peripheral blood. On the IOC device, uNK cells from naturally cycling secretory endometrium promote EVT invasion (P = 0.03). However, uNK cells from hormonally stimulated endometrium were unable to significantly promote EVT invasion, as measured by area of invasion, depth of invasion, and number of invaded EVTs by area. Bulk RNA-seq of sorted uNK cells from stimulated and unstimulated endometrium revealed changes in signaling pathways associated with immune cell trafficking/movement and inflammation.; Limitations, Reasons for Caution: Patient numbers utilized for the study were low but were enough to identify significant overall population differences in select immune cell types. With additional power and deeper immune phenotyping, we may detect additional differences in immune cell composition of blood and endometrium in the setting of hormonal stimulation. Flow cytometry was performed on targeted immune cell populations that have shown involvement in early pregnancy. A more unbiased approach might identify changes in novel maternal immune cells not investigated in this study. We performed RNA-seq only on uNK cells, which demonstrated differences in gene expression. Ovarian stimulation may also impact gene expression and function of other subsets of immune cells, as well as other cell types within the endometrium. Finally the IOC device, while a major improvement over existing in vitro methods to study early pregnancy, does not include all possible maternal cells present during early pregnancy, which could impact functional effects seen. Immune cells other than uNK cells may impact invasion of EVTs in vitro and in vivo, though these remain to be tested.; Wider Implications of the Findings: These findings demonstrate that hormonal stimulation affects the distribution of uNK cells during the implantation window and reduces the proinvasive effects of uNK cells during early pregnancy. Our results provide a potential mechanism by which fresh IVF cycles may increase risk of disorders of placentation, previously linked to adverse perinatal outcomes.; Study Funding/competing Interest(s): Research reported in this publication was supported by the University of Pennsylvania University Research Funding (to M.M.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD068157 to M.M., S.S., and S.M.), National Center for Advancing Translational Sciences of the National Institutes of Health (TL1TR001880 to J.K.), the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania, the Children's Hospital of Philadelphia Research Institute (to S.M.G.), and the National Institute of Allergy and Infectious Diseases (K08AI151265 to S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors declare no conflict of interest.; Trial Registration Number: N/A. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Kapoor, E. (2024). "Primary ovarian insufficiency: a toolkit for the busy clinician." Menopause (New York, N.Y.) 31(1): 65-67.
	Primary ovarian insufficiency (sometimes known as premature ovarian insufficiency) is a result of loss of ovarian follicular activity before the age of 40 years. It is an endocrine deficiency state in women, characterized by premature estrogen deprivation. In the absence of estrogen replacement, women experience bothersome menopause symptoms and a predisposition to accelerated aging and multimorbidity accumulation. Unless a true contraindication exists, estrogen therapy is recommended at least until the age of natural menopause. This Practice Pearl summarizes the clinical manifestations, diagnostic evaluation, and management of primary ovarian insufficiency. (Copyright © 2023 by The Menopause Society.)

Karaahmet, A. Y., et al. (2022). "Does perinatal period pelvic floor muscle exercises affect sexuality and pelvic muscle strength? A systematic review and meta-analysis of randomized controlled trials." Revista da Associacao Medica Brasileira (1992) 68(8): 1033-1041.
	OBJECTIVE: The aim of this study was to systematically review the effect of pelvic floor exercises on female sexual function and pelvic floor strength in the prenatal and postnatal periods and to conduct a meta-analysis of available evidence. METHODS: Published archives, including PubMed, Cochrane Library, Web of Science, and ULAKBİM databases, were scanned using keywords based on MeSH. Only randomized controlled trials were included. The data were analyzed using the Review Manager computer program (version 5.3). RESULTS: Pooled standardized differences in means of sexual function in both pelvic floor exercise and control group were 6.33 (95%CI 5.27-7.40, p<0.00001) during pregnancy. The pooled standardized differences in means in sexual function after postpartum intervention was 1.19 (95%CI 0.08--2.30, p=0.04). CONCLUSION: Evidence has shown a little effect on the pelvic floor muscle training on sexual function in pregnancy and postpartum period in primipara women, and it is a safe strategy that can improve postpartum sexual function.

Karaaslan, Y., et al. (2021). "Comparison of Pelvic Floor Muscle Training With Connective Tissue Massage to Pelvic Floor Muscle Training Alone in Women With Overactive Bladder: A Randomized Controlled Study." Journal of manipulative and physiological therapeutics 44(4): 295-306.
	OBJECTIVE: The purpose of this study was to compare the effects of a 6-week program of pelvic floor muscle training (PFMT) plus connective tissue massage (CTM) to PFMT alone in women with overactive bladder (OAB) symptoms on those symptoms, pelvic floor muscle strength, and quality of life. METHODS: Thirty-four participants were randomly divided into PFMT+CTM (n = 17) and PFMT (n = 17) groups. PFMT was applied every day and CTM was applied 3 days a week for 6 weeks. Before treatment, at week 3, and after treatment (week 6), we assessed pelvic floor muscle strength (with a perineometer), bladder symptoms (with a urine diary), OAB symptom severity (with the 8-item Overactive Bladder Questionnaire [OAB-V8]), urgency (with the Patient Perception of Intensity of Urgency Scale [PPIUS]), and quality of life (with King's Health Questionnaire [KHQ]). The Mann-Whitney U test, χ2 test, Friedman test, and Dunn multiple comparison test were used for analysis. RESULTS: In both groups, pelvic floor muscle strength increased, whereas OAB symptoms and PPIUS and KHQ scores decreased after treatment (P < .05). Although the OAB-V8, PPIUS, and KHQ scores decreased at week 3, frequency, OAB-V8, and PPIUS scores, in addition to some parameters of the KHQ, decreased after treatment in the PFMT+CTM group compared to the PFMT group (P < .05). CONCLUSION: Compared to PFMT alone, PFMT+CTM achieved superior outcomes in reducing OAB symptoms in the early and late periods.

Karageorgiou, V., et al. (2020). "Menopause in women with multiple sclerosis: A systematic review." Maturitas 135: 68-73.
	Aim: Sex hormones have been suggested to have neuroprotective effects in the natural history of multiple sclerosis (MS), particularly in animal studies. The aim of the present review was to retrieve and systematically synthesize the evidence on the effect of menopause and hormonal replacement treatment (HRT) on the course of MS.; Methods: A systematic literature search was conducted in the databases MEDLINE (accessed through PubMed), Scopus, clinicaltrials.gov and Cochrane Controlled Register of Trials (CENTRAL). Eligible studies were all those that included women with MS and reported on at least one of the following: a) disability and MS relapse rate before and after menopause, b) serum sex hormone concentrations, c) sexual function, d) age at menopause onset. Effects of HRT on MS clinical outcomes were also assessed.; Results: Of the 4,102 retrieved studies, 28 were included in the systematic review. Of these, one reported the age at menopause for both controls and women with MS and found no difference between the two groups. There was no difference in the rates of relapse before and after menopause (risk ratio 1.21, 95 % confidence interval 0.91-1.61, p = 0.218). Two intervention studies reported beneficial effects of estrogen therapy on women with MS; however, the majority of women were premenopausal. Three studies addressed the issue of sexual dysfunction in women with MS, but information on hormonal parameters was limited.; Conclusions: The age at menopause is not associated with the presence of MS. The evidence on a potential causal effect of estrogen depletion on disability is inconclusive; still, relapse rate seems not be associated with menopause. The effect of HRT on the natural course of the disease remains to be defined. (Copyright © 2020. Published by Elsevier B.V.)

Karakus, S. and E. Baysal (2022). "The effect of dark chocolate and music on pain and anxiety in young women with primary dysmenorrhea: Randomized controlled trial." European journal of integrative medicine 56: 102192.
	Introduction: Music medicine and dark chocolate may be potentially effective in helping reduce pain and anxiety in primary dysmenorrhea (PD). The aim of the study was to determine the effects of music medicine and dark chocolate on primary dysmenorrhea related pain intensity and anxiety level in young women. Method(s): This was was a non-blinded, three-parallel group randomized controlled trial. The study included 18-25-year-old nulliparous nursing students with PD having a regular menstruation cycle and a Visual Analog Scale (VAS) severity of menstrual pain of 5 and over during the previous 6 months. Ninety nursing students were randomly allocated into one of the three groups; dark chocolate, music, or control. The study was completed with 84 nursing students because some participants did not want to continue the study and used analgesics. In the first month, 84 students (chocolate: 30, music: 25, control: 29) completed the State-Trait Anxiety Inventory (STAI). In the second month, menstrual pain intensity and state anxiety were measured on the first day of menstruation using VAS and STAI, respectively, on 84 students. The dark chocolate group had dark chocolate for three days before menstruation and on the first day of menstruation in the third month. The music group listened to a song for the same four days. The pain scores and state anxiety were measured in all groups after the interventions. Result(s): Mean menstrual pain intensity and mean anxiety level in the dark chocolate and music group decreased significantly after the intervention. No significant difference was observed in the control group. The difference between menstrual pain intensity and anxiety levels of the groups was tested by analysis of variance, and the standardized effect size calculated at 95% confidence level, and alpha = 0.05 was 0.35 and 0.42, respectively. Conclusion(s): Both dark chocolate and music medicine significantly reduced menstrual pain and anxiety in young women with primary dysmenorrhea. Further research is needed to draw stronger conclusions on their impact on controlling menstrual pain and anxiety in primary dysmenorrhea as a nursing intervention. clinicaltrials.gov. (Clinical Trial registration number: NCT04911673).Copyright © 2022 Elsevier GmbH

Karam, A., et al. (2022). "CAR-T Cell Therapy for Solid Tumors: Are we Still That Far? a Systematic Review of Literature." Cancer Investigation 40(10): 923-937.
	This systematic review aims to assess all the prospective studies published to date on the efficacy of CAR-T cell therapy in solid tumors. Databases searched were PubMed and Google Scholar from inception through May 1st 2021. Search query was (Chimeric antigen receptor) or (CAR-T) or (T-CAR). Twenty-nine prospective studies (265 patients) were included. Most published clinical trials are phase I. Clinical benefit was 100% in epithelial ovarian cancer, 70-82% in gastrointestinal tumors, 79% in mesothelioma, 63% in small-cell lung cancer, 24-67% in sarcoma, 50-62% in prostate cancer, and 45-50% in central nervous system tumors. No serious CAR-T cell specific serious toxicities were noted.

Karampinis, I., et al. (2022). "Hyperthermic intrathoracic chemotherapy for the treatment of malignant pleural effusion caused by breast and ovarian cancer: A systematic literature review and pooled analysis." Thoracic cancer 13(7): 883-888.
	Objectives: Breast and ovarian cancer account for over 30% of malignant pleural effusions (MPEs). Treatment of the metastatic disease requires control of the MPE. Even though primarily symptomatic, the treatment of the MPE can potentially affect the oncological course of the disease. The aim of this review is to analyze the effectiveness of intrathoracic chemotherapy in the treatment of MPE caused by breast and ovarian cancer.; Methods: A systematic literature research was conducted up until May 2021. Studies published in English on patients undergoing either surgical or interventional intrapleural chemotherapy were included.; Results: Thirteen studies with a total of 497 patients were included. Analysis was performed on 169 patients with MPE due to breast cancer and eight patients with MPE secondary to ovarian cancer. The pooled success rates of intrathoracic chemotherapy for controlling the MPE were 59.1% and 87.5%, respectively. A survival analysis was not possible with the available data. The overall toxicity of the treatment was low.; Conclusions: Intrathoracic chemotherapy achieves symptomatic control of the MPE in 59.1% of patients with metastatic breast cancer and 87.5% of patients with metastatic ovarian cancer. This is inferior to other forms of surgical pleurodesis. Data from small case series and studies on intraperitoneal chemotherapy show promising results. However, formal oncological studies on the use of intrathoracic chemotherapy for metastatic breast or ovarian cancer are lacking. Further prospective pilot studies are needed to assess the therapeutic oncological effects of this treatment. (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Karanth, S., et al. (2019). "Race, Socioeconomic Status, and Health-Care Access Disparities in Ovarian Cancer Treatment and Mortality: Systematic Review and Meta-Analysis." JNCI Cancer Spectrum 3(4): pkz084.
	Background: Ovarian cancer remains a leading cause of death from gynecological malignancies. Race, socioeconomic status (SES), and access to health care are important predictors of quality treatment and survival. We provide a systematic review and meta-analysis on the role of these predictors on disparities in ovarian cancer treatment and mortality.; Methods: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched PubMed, EMBASE, and Scopus for relevant articles published between January 2000 and March 2017. We selected studies published in the United States that evaluated the role of race, SES, or health-care access on disparities in ovarian cancer treatment or survival. Pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated for each outcome using a random-effects model.; Results: A total of 41 studies met the inclusion criteria for systematic review. In meta-analysis, there was a 25% decrease (RR = 0.75, 95% CI = 0.66 to 0.84) in receipt of adherent ovarian cancer treatment and 18% increased risk (RR = 1.18, 95% CI = 1.11 to 1.26) of mortality for blacks compared to whites. Receipt of adherent ovarian cancer treatment was 15% lower (RR = 0.85, 95% CI = 0.77 to 0.94) in the lowest vs highest SES group and 30% lower (RR = 0.70, 95% CI = 0.58 to 0.85) among patients at lower vs higher hospital volumes.; Conclusion: We found consistent and strong evidence for continued lack of quality ovarian cancer treatment and higher mortality among ovarian cancer patients who are black, are of low SES, and/or have poor access to care. Interventions focused on these groups targeting specific barriers to care are needed to reduce disparities in ovarian cancer treatment and mortality. (© The Author(s) 2019. Published by Oxford University Press.)

Kargo Anette, S., et al. (2019). "Proactive use of PROMs in ovarian cancer survivors: a systematic review." Journal of Ovarian Research 12(1): 63.
	Introduction: The use of patient reported outcome measures (PROMs) has increased during the past decade, and the focus on how to use them has resulted in a more proactive application. Studies have shown that proactive use of PROMs during treatment improves patient-clinician communication, leads to better symptom management and may prolong survival among advanced cancer patients. Ovarian cancer is a serious disease in which the majority of patients experience recurrence during the follow-up period and suffer from a number of severe symptoms from underlying disease. This systematic review was conducted to assess the evidence on the proactive use of PROMs as a dialogue tool during follow-up of ovarian cancer patients.; Results: The following databases were searched for relevant literature; PubMed, EMBASE, CINAHL, and the Cochrane Library. The search was conducted in April 2019 without any filters or limits. A total of 643 publications were identified, and 48 studies were found to be potentially eligible. Of the 48 papers, none met the final inclusion criterion of using PROMs proactively as a dialogue tool for ovarian cancer patients during follow-up.; Conclusion: Studies have shown that PROMs can identify otherwise undetected symptoms. Using PROMs proactively during the consultation has been shown to improve symptom management for patients with some other types of cancer. However, we found no studies that had examined the proactive use of PROMs during follow-up of ovarian cancer patients. Future studies should evaluate if the proactive use of PROMs could facilitate a more individualized and more effective follow-up program tailored to the ovarian cancer patient's needs and preferences.

Kargozar, R., et al. (2024). "Phytoestrogens in Menopausal Hot Flashes: A Review Article." Current Traditional Medicine 10(4): 9-20.
	Background: Menopause is a biopsychosocial phenomenon in a woman's life, and it occurs at about the age of 48-55 years. Factors such as smoking, the number of children, early pu-berty, and social class can cause early natural menopause. Symptoms that occur during menopause include headache, mood disorders, insomnia, distraction, hot flashes, vaginal dryness, and sweat-ing. The most common symptom is hot flashes, which affect 85% of women with menopause. Re-cently, people are showing more tendencies toward alternative therapies and herbs phytoestrogens. Objective(s): This review aims to introduce the mechanism of herbal phytoestrogens controlling hot flashes during menopause. Method(s): Our searches were performed in the databases of PubMed, Scopus, and Cochrane. Eng-lish clinical trials, that investigated the effects of phytoestrogen plants individually or in combination on the treatment of hot flashes in menopause were analyzed. After reviewing articles and meeting the inclusion and exclusion criteria, 18 articles were selected. Result(s): In this study, 18 clinical trials of 2351 female patients were analyzed. The phytoestrogen plants studied include soy, red clover, cohosh, hops, flax, pomegranate, anise, and Vitex Agnus. Conclusion(s): Studies have shown the beneficial effects of phytoestrogens in controlling hot flashes, but in some cases, including soybeans, there are contradictory effects. Therefore, more clinical trials are needed to achieve reliable results to confirm the phytoestrogen effects of herbal medicines.Copyright © 2024 Bentham Science Publishers.

Karim, S. S., et al. (2020). "Role of endoscopic management in synthetic sling/mesh erosion following previous incontinence surgery: a systematic review from European Association of Urologists Young Academic Urologists (YAU) and Uro-technology (ESUT) groups." International Urogynecology Journal 31(1): 45-53.
	INTRODUCTION AND HYPOTHESIS: Foreign body (FB) erosion is now recognized as a major long-term complication following previous incontinence surgery. The aim of our systematic review was to ascertain the outcomes of endoscopic management in synthetic sling/mesh erosion following previous gynaecological surgery. METHODS: A systematic review in line with PRISMA and Cochrane guidelines was conducted for all English language articles between 1996 and December 2018 for all articles reporting on endoscopic surgical management for eroded FB following previous sling/mesh procedure for incontinence. RESULTS: Our search produced 931 articles of which 20 articles (198 patients) were included in our review; 149 (75%) had tension-free vaginal tapes (TVT) or tension-free obturator tapes (TOT) as their initial procedure. The site of mesh erosion was the bladder in 134 patients (68%) of which 12 (6%) were in the bladder neck. Urethral mesh erosion was seen in 63 patients (32%) across all studies. The treatment of eroded mesh was by laser and endoscopic excision using an electrode loop or laparoscopic scissors in 108 (55%) and 90 (45%) patients respectively. The initial/final success rate with laser and endoscopic excision was 67%/92% and 80%/98% respectively. The overall complication rates were 24% and 28% in laser and endoscopic groups respectively of which 21% in each group were stress urinary incontinence. CONCLUSIONS: Endoscopic management of FB erosion is an effective minimally invasive technique with good outcomes and minimal morbidity. Management with the use of holmium laser is gaining momentum and could be attempted before open surgical removal. There is a need for comparative data between open surgical excision and endoscopic excision to help better describe the patient's most likely to benefit from the endoscopic technique.

Karine, E., et al. (2023). "Vaginal CO2 laser therapy versus sham for genitourinary syndrome of menopause management: a systematic review and updated meta-analysis of randomized controlled trials." PROSPERO International prospective register of systematic reviews.
	
Karp Barbara, I. and P. Stratton (2023). "Applications of botulinum toxin to the female pelvic floor: Botulinum toxin for genito-pelvic pain penetration disorder and chronic pelvic pain in women." Toxicon : official journal of the International Society on Toxinology 230: 107162.
	Chronic pain conditions like genito-pelvic pain penetration disorder and chronic pelvic pain cause significant morbidity in women worldwide and yet are underdiagnosed and undertreated. While the use of botulinum toxin for pain conditions has expanded, there are few randomized controlled studies of botulinum toxin for pelvic pain conditions in women. This paper provides an update on the current status and context for considering botulinum toxin treatment for these conditions to complement and expand currently available approaches. High quality clinical trials to evaluate safety and efficacy and to determine optimal doses and approaches to injection are urgently needed.; Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Allergan US provided monitoring funds and drug to the National Institutes of Health for an in-progress clinical trial mentioned in this paper. (Published by Elsevier Ltd.)

Karp, D. D., et al. (2022). "Phase I study of PT-112, a novel pyrophosphate-platinum immunogenic cell death inducer, in advanced solid tumours." EClinicalMedicine 49: 101430.
	Background: PT-112, the first pyrophosphate-platinum conjugate, causes immunogenic cell death in experimental models, leading to recruitment of tumour-infiltrating lymphocytes. PT-112 also associates with bone (osteotropism), likely driven by its pyrophosphate moiety. This is the first-in-human study of PT-112 monotherapy, exploring its safety and efficacy in a patient population where standard of care therapies were exhausted and novel treatment options are needed. Method(s): Patients with progressing, advanced solid tumours received PT-112 intravenously (1 h) on days 1, 8, 15 of a 28-day cycle in an open-label, multi-centre 3 + 3 dose-escalation trial, conducted at four US research sites. The primary objective was to assess safety and pharmacokinetics, and to identify a recommended phase 2 dose (RP2D). Eligibility criteria included: age >=18 years, Eastern Collaborative Oncology Group (ECOG) Performance Status of 0-1, and disease evaluable by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 or by informative tumour markers. Patients receiving >=1 dose of PT-112 were included in the safety and pharmacokinetic analyses, with the exploratory efficacy analysis including patients receiving >=1 dose at 125 mg/m2. This study is registered at ClinicalTrials.gov, number NCT02266745, with the dose-escalation portion of the study closed. Finding(s): Between July 7th, 2014 and September 18th, 2018, 66 heavily pre-treated patients (median 4 prior lines, IQR 2-6) were enrolled and treated across 11 doses (12-420 mg/m2). Treatment-related adverse events included fatigue (23 patients, 35%), nausea (16 patients, 24%), and peripheral neuropathy (14 patients, 21%). Grade 3 events were experienced by 18 patients (27%), with no grade 4-5 events observed. The recommended phase 2 dose was determined to be 360 mg/m2. Nine (17%) of the 54 efficacy evaluable patients achieved progression-free survival >=6 months. Durable partial responses were induced in non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and thymoma. Radiographic and serum marker reductions were observed among ten patients with metastatic castration resistant prostate cancer, four of whom survived two years or longer. Interpretation(s): PT-112 is safe and well-tolerated in a heavily pre-treated population. Prolonged responses were noted against thymoma and lung cancer, along with radiographic and serum marker improvement in prostate cancer. Given the heterogeneous patient population, subsequent studies will be needed to characterize the risk/benefit ratio in more homogenous settings. Further development of PT-112 is ongoing, as single-agent and in combination with immune checkpoint inhibition. Funding(s): Funding was provided by Promontory Therapeutics Inc.Copyright © 2022

Karpel, H., et al. (2023). "Biomarker-driven therapy in endometrial cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(3): 343-350.
	This article reviews treatments and targets of interest in endometrial cancer by molecular subtype. The Cancer Genome Atlas (TCGA) classifies four molecular subtypes-mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H); copy number high (CNH)/p53abn; copy number low (CNL)/no specific molecular profile (NSMP); and POLEmut-which are validated and highly prognostic. Treatment consideration by subtype is now recommended. In March and April 2022, respectively, the US Food and Drug Administration (FDA) fully approved and the European Medicines Agency adopted a positive opinion recommending the anti-programmed cell death protein-1 (PD-1) antibody pembrolizumab for advanced/recurrent dMMR/MSI-H endometrial cancer which has progressed on or following a platinum-containing therapy. A second anti-PD-1, dostarlimab, received accelerated approval by the FDA and conditional marketing authorization by the European Medicines Agency in this group. The combination of pembrolizumab/lenvatinib for mismatch repair proficient/microsatellite stable endometrial cancer, including p53abn/CNH and NSMP/CNL, received accelerated FDA approval in conjunction with Australia's Therapeutic Goods Administration and Health Canada in September 2019. The FDA and European Medicines Agency made full recommendations in July 2021 and October 2021. Trastuzumab is National Comprehensive Cancer Network (NCCN) compendium listed for human epidermal growth factor receptor-2-positive serous endometrial cancer, which is primarily within the p53abn/CNH subtype. In addition to hormonal therapy, maintenance therapy with selinexor (exportin-1 inhibitor) showed potential benefit in p53 -wildtype cases in a subset analysis and is being investigated prospectively. Other treatment regimens being evaluated in NSMP/CNL are hormonal combinations with cyclin-dependent kinase 4/6 inhibitors and letrozole. Ongoing trials are evaluating immunotherapy in combination with frontline chemotherapy and other targeted agents. Treatment de-escalation is being evaluated in POLEmut cases given its favorable prognosis with or without adjuvant therapy. Molecular subtyping has important prognostic and therapeutic implications, and should guide patient management and clinical trial design in endometrial cancer, which is a molecularly driven disease.; Competing Interests: Competing interests: BS reports consulting fees and payment for educational events outside the submitted work including from AstraZeneca, Clovis, GSK, Genentech, Merck, Eisai, Lilly, Novartis, Genmab, Seagen, Immunogen, Karyopharm, and Seagen. RLC reports grants, consulting fees and payment for educational events outside the submitted work including from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Janssen, Roche/Genentech, Agenus, Alkermes, Deciphera, GSK, OncoQuest, Onxerna, Regeneron, Novocure, Abbvie. Compensated advisory boards include VBL Therapeutics. BP reports grants, personal fees and non-financial support outside the submitted work; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genetech/Roche, Celsion, Karyopharm, Mersana, Takeda Pharmaceuticals, Eisai, and Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Mersana, Merck, Clovis Oncology, Eisai, Lily, Toray, Sutro and GOG Foundation. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Kartos, T., et al. (2023). Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer.
	No Results Available Drug: Navtemadlin|Drug: Navtemadlin Placebo Part 1: To determine the navtemadlin Phase 3 dose|Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo|Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment|Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST)|Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin|Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR) Female Phase 2|Phase 3 268 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment KRT-232-118|ENGOT en-21|GOG-3089 July 2027

Kasamatsu, T. and T. Arimoto (2022). "Phase III clinical trials of radical hysterectomy with minimal parametrectomy for patients with early-stage cervical cancer: a review." European Journal of Gynaecological Oncology 43(4): 12-18.
	The standard surgery for patients with International Federation Gynecology and Obstetrics (FIGO) stage IB-II cervical cancer is a Piver-Rutledge-Smith class III radical hysterectomy with pelvic lymphadenectomy involving a wide resection of parametrial and paravaginal tissue to control parametrial involvement. However, adverse events can occur such as severe long-term neurogenic bladder due to parametrectomy. This review evaluates ongoing and completed phase III clinical trials of less radical hysterectomy with regard to parametrectomy. The PubMed database, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials were used to extract information on two completed and four ongoing clinical trials. Less radical surgery led to similar oncologic outcomes to standard surgery in two phase III randomized controlled trials (Piver class II vs. class III, and class I vs. class III radical hysterectomy with pelvic lymphadenectomy). Less radical surgery also led to fewer complications, including urologic morbidity; however, more than 50% of patients received radiotherapy following such surgery, and showed higher morbidity rates because their enrolment was due to the presence of a large tumor (>4 cm). Three phase III randomized controlled trials and a phase III nonrandomized confirmatory trial are presently ongoing. Major inclusion criteria include FIGO stage IA, IB, or IIA1, a mainly <=2-cm tumor, limited depth of stromal invasion, and/or no lymph node metastasis. Surgery for the standard arm is a class II or class III radical hysterectomy, and the experimental surgery is a simple extrafascial hysterectomy or class II radical hysterectomy. Primary endpoints are overall, disease-free, or recurrence-free survival. Although primary endpoints, eligibilities or types of radical hysterectomy differ between trials, if noninferiority in overall, disease-free or recurrence-free survival is observed in any trial, new standard, less radical, curative hysterectomy may be established for early-stage, small-sized, invasive, cervical cancer.Copyright © 2022 The Author(s).

Kashef, E., et al. (2023). "Pelvic venous congestion syndrome: female venous congestive syndromes and endovascular treatment options." CVIR endovascular 6(1): 25.
	Pelvic venous congestion syndrome (PVCS) is a common, but underdiagnosed, cause of chronic pelvic pain (CPP) in women.PVCS occurs usually, but not exclusively, in multiparous women. It is characterized by chronic pelvic pain of more than six months duration with no evidence of inflammatory disease.The patients present to general practitioners, gynaecologists, vascular specialists, pain specialists, gastroenterologists and psychiatrists. Pain of variable intensity occurs at any time but is worse in the pre-menstrual period, and is exacerbated by walking, standing, and fatigue. Post coital ache, dysmenorrhea, dyspareunia, bladder irritability and rectal discomfort are also common. Under-diagnosis of this condition can lead to anxiety and depression.A multidisciplinary approach in the investigation and management of these women is vital.Non-invasive imaging (US, CT, MRI) are essential in the diagnosis and exclusion of other conditions that cause CPP as well in the definitive diagnosis of PVCS. Trans-catheter venography remains the gold standard modality for the definitive diagnosis and is undertaken as an immediate precursor to ovarian vein embolization (OVE). Conservative, medical and surgical management strategies have been reported but have been superseded by OVE, which has a reported technical success rates of 96-100%, low complication rates and long-term symptomatic relief in between 70-90% of cases.The condition, described in this paper as PVCS, is referred to by a wide variety of other terms in the literature, a cause of confusion.There is a significant body of literature describing the syndrome and the excellent outcomes following OVE however the lack of prospective, multicentre randomized controlled trials for both investigation and management of PVCS is a significant barrier to the complete acceptance of both the existence, investigation and management of the condition. (© 2023. The Author(s).)

Kasius, J. C., et al. (2021). "Neo-adjuvant chemotherapy in fertility-sparing cervical cancer treatment." Best Practice and Research: Clinical Obstetrics and Gynaecology 75: 82-100.
	The current review provides a literature overview of studies assessing the oncological and fertility outcomes of treatment with neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer >2 cm. Six cohort studies were included showing severe heterogeneity regarding patient selection, chemotherapy regimen, and surgical approach. In total, 111 patients were studied, with overall favorable characteristics. Patients were on average 29 years old, had a tumor of 36 mm, no lymph node metastasis, and response to chemotherapy. In approximately 5-year follow-up, the recurrence rate was 13% (0%-21%) and overall death rate 2.7% (0%-10%). Three patients were alive with recurrent disease (2.7% and 0%-11%). Of the 111 patients, 90 underwent successful fertility-sparing treatment (83%). Roughly one-third conceived and one-fourth had a healthy live-born child. More research is essential to determine proper selection criteria for fertility-sparing treatment of cervical cancer >2 cm and the optimal treatment management.Copyright © 2021

Kasman, A., et al. (2019). "Combination therapy in overactive bladder-untapped research opportunities: A systematic review of the literature." Neurourology and Urodynamics 38(8): 2083-2092.
	Aims: Overactive bladder (OAB) affects over 17% of the population and significantly effect the health-related quality of life. The treatments for OAB include first line (lifestyle modification, pelvic floor muscle training), second line (anticholinergic or beta-3 agonist medications), and third line therapies (intradetrusor botulinum toxin injection, sacral neurostimulation [SNM], or percutaneous tibial nerve stimulation [PTNS]). For those with urinary incontinence secondary to OAB, complete continence is the goal of therapy, though cure rates are only 5% to 40%. The use of combination therapies can be employed in refractory OAB, however, the efficacy of pooled modalities is relatively unknown. Our objective was to determine the volume of data supporting combination therapy in treating OAB. Method(s): We systematically reviewed PubMed, EMBASE, the Cochrane Library, and Google Scholar for articles published before October 2018. Each was independently reviewed by two reviewers and examined in detail if they met inclusion criteria. Result(s): A total of 32 studies met inclusion criteria and were reviewed. Most large prospective studies evaluated combinations of medications with behavioral therapy or medications together. Combination therapy studies of third-line treatments were rare and centered on medication with PTNS. No studies examined intradetrusor botulinum toxin injections in combination with another therapy and only one retrospective study briefly examined SNM therapy in combination with medication. Conclusion(s): Combination therapy, with certain first, second, and third-line OAB therapies, appears to be efficacious. There is a further need for carefully designed combination therapy studies, particularly those including third line modalities.Copyright © 2019 Wiley Periodicals, Inc.

Kataoka, J., et al. (2022). "Circulating Anti-Müllerian hormone in a cohort-study of women with severe obesity with and without polycystic ovary syndrome and the effect of a one-year weight loss intervention." Reproductive biology and endocrinology : RB&E 20(1): 153.
	Background: Women with polycystic ovary syndrome (PCOS) have high circulating anti-Müllerian hormone (AMH) levels which is correlated with antral follicle count and polycystic ovarian morphology and negatively correlated with body mass index (BMI). Moreover, diet-induced weight loss in women with PCOS and overweight or obesity, reduce or normalize AMH-levels. There is, however, no previous study investigating the circulating AMH levels in women with severe obesity and how a structured diet-induced weight loss program affects circulating AMH levels in these women. Therefore, this study aims to investigate circulating AMH levels in a population of women with severe obesity (BMI ≥ 35 kg/m 2 ) with and without PCOS, as diagnosed by the NIH-criteria, and to investigate the effect of a one-year weight loss program with a very low-energy diet (VLED) on circulating levels of AMH.; Methods: In a prospective cohort-study, were 246 women with severe obesity were screened for PCOS diagnosis with the NIH-criteria, circulating AMH and anthropometry were measured at baseline and after a 12-month weight loss intervention with very low-energy diet (VLED).; Results: Mean BMI was 39.9 ± 4.7 (PCOS), 39.6 ± 4.3 (non-PCOS) P = 0.960. Circulating AMH was higher in women with PCOS (5.47 ± 4.89 µg/L) compared with non-PCOS (2.66 ± 3.71 µg/L) P < 0.001 and was positively correlated with circulating total testosterone in both groups. Next, we performed ROC-analyses, and show that circulating AMH could not discriminate women with PCOS and severe obesity from non-PCOS women with severe obesity. Finally, a one-year weight reduction program does not affect circulating AMH levels despite significant weight loss neither in women with PCOS, nor without PCOS and severe obesity.; Conclusion: Women with severe obesity and PCOS have elevated levels of circulating AMH compared to women without the syndrome. AMH-levels could not discriminate women with PCOS from non-PCOS because of low sensitivity and specificity. Significant weight loss was not associated with changes in circulating AMH levels, neither in women with, nor without PCOS and severe obesity. These results imply that in women with severe obesity, a greater weight loss may be needed to improve reproductive features, independent of PCOS diagnosis.; Trial Registration Number: Clinical trial.gov: NCT01319162. (© 2022. The Author(s).)

Katherine, R. and W. Chaston (2023). "Outcomes of probiotic use in the treatment of bacterial vaginosis in pregnant women: a meta-analysis."
	
Kathopoulis, N., et al. (2022). "The Effect of Intravenous Tranexamic Acid on Myomectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Journal of Personalized Medicine 12(9).
	Myomectomy is the preferred surgical treatment for symptomatic women with uterine myomas who wish to preserve their fertility. The procedure may be associated with significant intraoperative blood loss, which predisposes to increased transfusion rates and morbidity. The objective of our systematic review and meta-analysis is to investigate whether intravenous (IV) use of tranexamic acid (TXA) may reduce blood loss during myomectomy. Three electronic databases were screened until June 2022. The eligible studies were assessed for risk of bias. Four randomized controlled trials that reported outcomes from a total of 310 women were finally included in the meta-analysis-155 patients received intravenous TXA while the remaining 155 received placebo injection with normal saline or water for injection. Total estimated blood loss was significantly lower in patients who received TXA before myomectomy compared to control (230 patients MD -227.09 mL 95% CI -426.26, -27.91, p = 0.03). This difference in favor of TXA group remained when intraoperative and postoperative blood loss was separately analyzed. Postoperative hematocrit values and hemoglobin levels did not differ among the two groups (180 patients MD 0.67% 95% CI -0.26, 1.59, p = 0.16 and 250 patients MD 0.17 mg/dL 95% CI 0.07, 0.41, p = 0.17, respectively). The number of patients that received blood transfusion was also not different (310 patients OR 0.46 95% CI -0.14, 1.49, p = 0.19). Total operative time was significantly prolonged in control group compared to TXA (310 patients MD -16.39 min 95% CI -31.44, -1.34 p = 0.03). Our data show that the IV use of TXA may significantly reduce intraoperative blood loss in patients undergoing myomectomy and contribute to reduced operative time.

Kathopoulis, N., et al. (2022). "Deep Versus Moderate Neuromuscular Blockade in Gynecologic Laparoscopic Operations: randomized Controlled Trial." Journal of Personalized Medicine 12(4).
	Background: To investigate whether deep neuromuscular blockade (NMB) improves surgical conditions and postoperative pain compared to moderate block, in patients undergoing gynecologic laparoscopic surgery. Methods: A single blind, randomized, controlled trial was undertaken with laparoscopic gynecologic surgical patients, who were randomly assigned to one of the following two groups: patients in the first group received deep NMB (PTC 0‐1) and in the other, moderate NMB (TOF 0‐1). Primary outcomes included assessing the surgical conditions using a four‐grade scale, ranging from 0 (extremely poor) to 3 (optimal), and patients’ postoperative pain was evaluated with a five‐grade Likert scale and the analgesic consumption. Results: 144 patients were analyzed as follows: 73 patients received deep NMB and 71 moderate NMB. Mean surgical field scores were comparable between the two groups (2.44 for moderate vs. 2.68 for deep NMB). Regarding postoperative pain scores, the patients in the deep NMB experienced significantly less pain than in the group of moderate NMB (0.79 vs. 1.58, p < 0.001). Moreover, when the consumption of analgesic drugs was compared, the moderate NMB group needed more extra opioid analgesia than the deep NMB group (18.3% vs. 4.1%, p = 0.007). From the secondary endpoints, an interesting finding of the study was that patients on deep NMB had significantly fewer incidents of subcutaneous emphysema. Conclusions: Our data show that, during the performance of gynecologic laparoscopic surgery, deep NMB offers no advantage of operating filed conditions compared with moderate NMB. Patients may benefit from the deep block as it may reduce postoperative pain.

Katipally, R. R., et al. (2022). "The oligometastatic spectrum in the era of improved detection and modern systemic therapy." Nature Reviews Clinical Oncology 19(9): 585-599.
	Metastases remain the leading cause of cancer-related mortality. The oligometastasis hypothesis postulates that a spectrum of metastatic spread exists and that some patients with a limited burden of metastases can be cured with ablative therapy. Over the past decade, substantial advances in systemic therapies have resulted in considerable improvements in the outcomes of patients with metastatic cancers, warranting re-examination of the oligometastatic paradigm and the role of local ablative therapies within the context of the improved therapeutic responses, shifting patterns of disease recurrence and possible synergy with systemic treatments. Herein, we reframe the oligometastatic phenotype as a dynamic state for which locally ablative, metastasis-directed therapy improves clinical outcomes, including by prolonging survival and increasing cure rates. Important risk factors defining the metastatic spectrum are highlighted that inform both staging and therapy. Finally, we synthesize the literature on combining local therapies with modern systemic treatments, identifying general themes to optimally integrate ablative therapies in this context.Copyright © 2022, Springer Nature Limited.

Katke, A., et al. (2021). "Weekly vs. tri-weekly cisplatin based chemoradiation in carcinoma cervix: a prospective randomized study of toxicity and compliance." Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology 26(6): 948-954.
	BACKGROUND: Addition of chemotherapy to radiation has improved 5-year survival by 6%. However, the optimal dose and schedule of concurrent cisplatin is not well defined, though widely accepted practice is the weekly schedule of 40 mg/m2 for 5 weeks. Repeated admissions for weekly cisplatin drain the limited resources in high volume centres. We intended to study the compliance and toxicity of two cisplatin schedules in our patients diagnosed with carcinoma cervix. MATERIALS AND METHODS: Between 2007-2011, 212 patients, histologically proven squamous cell carcinoma with stages IIB to IIIB were randomized into two arms. All patients were planned for external beam radiotherapy 45 Gy/25 frs over 5 weeks followed by Intracavitary or Interstitial brachytherapy to a total BED dose of 75-85 Gy. Single agent cisplatin given concomitantly, was scheduled weekly (40 mg/m2/cycle, 5 cycles) in an arm A and three weekly (100 mg/m2/cycle, 2 cycles) in an arm B. Toxicity and compliance were evaluated weekly according to the RTOG guidelines. Analysis of the compiled data was done using SSPS version 20. RESULTS: Of the evaluable 212, 109 patients received weekly cisplatin chemotherapy and 103 patients received three weekly cisplatin. The most common acute toxicity observed was grade I-II leucopoenia. The upper and lower gastrointestinal reactions were high in three weekly arms, which was statistically significant (57% and 42.7%, p < 0.05). Proctitis was observed in 10% of patients in both of the arms and only two patients had Gr1 Cystitis after 6 months of treatment. CONCLUSIONS: Tri-weekly cisplatin based concurrent chemoradiation can be adopted in high volume centres with manageable haematological and gastrointestinal acute toxicities.

Kato, H., et al. (2022). "Systematic review and meta-analysis for impacts of oral antibiotic treatment on pregnancy outcomes in chronic endometritis patients." Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28(5): 610-615.
	Background: Chronic endometritis is a persistent inflammatory condition of the endometrium that negatively affects pregnancy outcomes. The Centers for Disease Control and Prevention guidelines recommend oral antibiotic treatment for chronic endometritis. However, a recent randomized controlled trial concluded that it was unclear whether antibiotic treatment improved pregnancy outcomes. Hence, we performed a systematic review and meta-analysis to validate the impact of oral antibiotic treatments on pregnancy outcomes among patients with chronic endometritis.; Methods: We systematically searched the PubMed, Scopus, Ichushi, CINAHL, and EMBASE databases until May 2021. We compared the pregnancy outcomes in patients with chronic endometritis with and without antibiotic treatment. We then focused on the implantation rate, intrauterine pregnancy rate, and live birth rate to evaluate pregnancy outcomes.; Results: Seven studies were included in the meta-analysis. Three hundred seventy-two patients were treated with antibiotics, while 1024 patients were not treated with antibiotics. Various antibiotic regimens were administered during the study period [14-21 days]. Antibiotic treatments for chronic endometritis did not increase the implantation rate (odds ratios [OR] 1.02, 95% confidence interval [CI], 0.78-1.33), intrauterine pregnancy rate (OR 1.08, 95% CI 0.72-1.63), or live birth rate (OR 1.13, 95% CI 0.65-1.97).; Conclusions: Our meta-analysis proved that oral antibiotic treatment did not improve pregnancy outcomes in patients with chronic endometritis. Accordingly, further studies are needed to elucidate the treatment to improve pregnancy outcomes. (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Kato, K., et al. (2023). "Preimplantation Genetic Testing for Aneuploidy for Recurrent Pregnancy Loss and Recurrent Implantation Failure in Minimal Ovarian Stimulation Cycle for Women Aged 35-42 Years: Live Birth Rate, Developmental Follow-up of Children, and Embryo Ranking." Reproductive sciences (Thousand Oaks, Calif.) 30(3): 974-983.
	This study was aimed at exploring the benefits of preimplantation genetic testing for aneuploidy (PGT-A) in ensuring a successful pregnancy in patients with recurrent pregnancy loss (RPL) caused by an abnormal number of chromosomes in the embryo and recurrent implantation failure (RIF). Thirty-two patients who underwent PGT-A (18 in the RIF protocol and 14 in the RPL protocol) were enrolled in the study, and 2556 patients who did not undergo PGT-A during the same in vitro fertilization (IVF) treatment period were enrolled as controls. All patients underwent minimal stimulation cycle IVF. In the RPL protocol, the live birth rate per embryo transfer (ET) and that per patient were higher with PGT-A (80.0% each) than without it (0% each; P = 0.0050), and the rate of miscarriages was lower with PGT-A than without it (20.0% vs. 100.0%, P = 0.0098). In the RIF protocol, there were no significant differences in the live birth rate per ET and in the rate of miscarriages between groups with and without PGT-A-90.0% vs. 69.2% (P = 0.2313) and 0% vs. 10.0% (P = 0.3297), respectively. None of the children whose mothers underwent PGT-A presented adverse findings at a 1.5-year developmental check-up. In conclusion, PGT-A in RPL is advantageous for improving the live birth rate per ET and that per patient in minimal stimulation cycle IVF; it reduces the rate of miscarriages. In addition, PGT-A might be more beneficial for embryo selection than the existing morphological grades of blastocysts, resulting in earlier conception. (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Katy, W., et al. (2022). "Update of a systematic literature review of clinical effects, safety and patient-reported outcomes of treatment for previously treated, recurrent or metastatic cervical cancer."
	
Katyal, N., et al. (2021). "The association between psychosocial interventions and fertility treatment outcome: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 259: 125-132.
	Objective: Does psychosocial intervention affect pregnancy outcomes in women and couples undergoing assisted reproductive technology (ART) treatment?.; Design: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) evaluating the efficacy of psychosocial intervention on pregnancy outcomes in women and couples undergoing ART treatment. The primary outcome was Pregnancy Rates. Secondary outcomes were Live Birth Rate (LBR) and Abortion Rate (AR).; Materials and Methods: Databases searched were Pubmed, PsycINFO, Embase, CINAHL and The Cochrane Library. 1439 records were screened, 15 were eligible and included in the meta-analyses (N = 2434). Data was extracted using the Covidence software. Effect sizes were reported as relative risks with 95% confidence-intervals and p-values.; Results: A positive association was found between psychosocial intervention and pregnancy rates (RR = 1.12 CI=(1.01;1.24), p = 0.033). Long-duration interventions and mind-body intervention types were found to be associated with increased pregnancy rates (RR 1.21, CI= (1.04;1.43), p = 0.017) and (RR = 1.25, CI= (1.00;1.55), p = 0.046) respectively. Q and I 2 tests suggested no to low heterogeneity. Funnel plots, Trim and Fill analyses and Fail-safe numbers were applied to adjust for possible publication bias.; Conclusions: Our findings suggest a positive association between psychosocial interventions, particularly long-duration interventions, and pregnancy rate in infertile women and couples in ART treatment. The findings are in line with findings from other reviews and meta-analyses exploring the same topic. More good quality RCTs need to be performed to increase the quality of guidance for infertile women and couples. The effect of psychosocial interventions on LBR and AR remain to be examined.; Competing Interests: Declaration of Competing Interest The authors report no declarations of interest. (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Katz, C. M. S. and C. P. Barbosa (2024). "Effects of hypopressive exercises on pelvic floor and abdominal muscles in adult women: A systematic review of randomized clinical trials." Journal of Bodywork and Movement Therapies 37: 38-45.
	Introduction: Hypopressive exercises (HE) are postural and breathing exercises that activate deep muscles in the abdomen and pelvic floor. Despite this, there is still no consensus in the literature on its real effectiveness. The objective was to analyze the effects of HE on the abdominal and pelvic floor muscles in women with or without dysfunctions in these regions. Method(s): This is a systematic review of randomized clinical trials found in the PEDro, PubMed, Cochrane, LILACS, and Embase databases. We include studies that evaluate the effects of HE (with or without other techniques) on the pelvic floor and abdominal region for 8 weeks or more, in women over 18 years old, with or without dysfunction in these regions, with the presence of a control group (active or passive). Result(s): HE were effective in improving strength, tone, and reducing symptoms of pelvic floor dysfunctions, in magnitude less than (in two studies) or equal (in one study) to the pelvic floor muscle training (PFMT). When HE were performed with PFMT in the same group, no additional benefits were found. Only one study evaluated abdominal muscles activation, where HE were effective in improving postural control and activation of the transversus abdominis muscle. Conclusion(s): The HE presented positive results to the evaluated parameters. However, the information is still preliminary and scarce. There are methodological divergences regarding the execution, follow-up and standardization of the method, which could affect the results. According to the existing information, HE cannot yet be reliably indicated for the treatment of the pelvic floor, despite pointing out relevant results in some studies. More randomized clinical trials and long-term studies are needed to analyze the effects of HE not only for pelvic floor, but also for other regions, such as abdominal muscles and related dysfunctions.Copyright © 2023 Elsevier Ltd

Kauffman, R. P. (2022). "In women with stress UI, device-guided pelvic floor muscle training safely improved symptoms more than self-guided training." Annals of Internal Medicine 175(7): JC79.
	ACP Journal Club SOURCE CITATION: Weinstein MM, Dunivan G, Guaderrama NM, et al. Digital therapeutic device for urinary incontinence: a randomized controlled trial. Obstet Gynecol. 2022;139:606-15. 35271539.

Kaufman, M. R., et al. (2021). "A double-blind, randomized, controlled trial comparing safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) with placebo (PBO) in women with stress urinary incontinence (SUI)." Journal of urology 206(SUPPL 3): e99.
	INTRODUCTION AND OBJECTIVE: This multicenter Phase 3 study (NCT01893138) evaluated efficacy and safety of AMDC‐USR compared to PBO for SUI treatment. METHODS: 297 adult women with average 14.4 ± 11.4 stress leaks over 3 days were randomized 2:1 (150x106AMDC‐USR:vehicle PBO) and stratified by baseline severity and prior SUI surgery. AMDC‐USR was manufactured from vastus lateralis harvest via outpatient biopsy and injected into the urinary sphincter at a subsequent outpatient procedure. SUI was monitored by 3‐day diary of stress incontinence episode frequency (SIEF) and quality of life (QOL) questionnaires. Subjects were unblinded after 12 months, and PBO subjects could receive an open‐label AMDC‐USR treatment. Subjects were followed for 2 years post initial treatment. RESULTS: 297 women were treated (199 AMDC‐USR; 98 PBO), 99% completed 12 months (199 AMDC‐USR; 96 PBO), and 85% have completed 2 years (167 AMDC‐USR; 86 PBO). 93% PBO subjects opted to receive open‐label AMDC‐USR treatment. Percentage of SIEF responders by strata, endpoints and visits is presented below. SIEF reduction correlated with improvement in all QOL scores at 12 months (p < 0.001). Treatment‐related serious adverse reactions were uncommon (< 1%) with no AMDC‐USR safety signals detected. CONCLUSIONS: Single injection of AMDC‐USR is safe and durable through 2 years with varying therapeutic effect. Consistent with our previous study,≥50% SIEF reduction is not a sufficient endpoint. High variability in PBO response rates across strata impacts generalizability of the treatment response in the overall population. Nonetheless, there was encouraging response in subjects with > 10 baseline SIE, and a markedly greater percentage (> 2‐fold) of women with prior surgery achieved statistical and clinically meaningful≥75% SIEF reduction compared with PBO, further supporting that this population may be ideally suited for AMDC‐USR therapy.

Kaufman, Y., et al. (2022). "Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants." Therapeutic advances in psychopharmacology 12: 20451253211065859.
	Postpartum depression is one of the most common morbidities of childbearing, yet it is underdiagnosed and undertreated with negative consequences for mother and offspring. Despite the widespread use of standard-of-care antidepressants as the mainstay of treatment for postpartum depression, there is limited evidence on their safety and efficacy due to their slow onset of action and suboptimal outcomes. The emergence of gamma-aminobutyric acidergic neuroactive steroids may offer faster response and remission times and improved patient outcomes. This article reviews the evidence base for the efficacy of standard-of-care antidepressants, hormonal therapeutics including progestins and estradiol, and gamma-aminobutyric acidergic neuroactive steroids in the treatment of postpartum depression, as well as the safety of infant exposure to these agents during lactation.; Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Deligiannidis serves as a consultant to Sage Therapeutics, Inc, and Brii Biosciences, and reports grants awarded to Zucker Hillside Hospital/Feinstein Institutes for Medical Research during the conduct of the brexanolone injection and zuranolone clinical trials. Dr Deligiannidis received grants from the National Institutes of Health (NIH) and Vorso Corporation and royalties from an NIH employee invention outside of the submitted work. Drs Kaufman and Carlini have no conflicts of interest to declare. (© The Author(s), 2022.)

Kaur, V., et al. (2021). "Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome." Metabolism: clinical and experimental 125: 154908.
	BACKGROUND: Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS: Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS: A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS: These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.

Kautz-Freimuth, S., et al. (2022). "Evaluation of two evidence-based decision aids for female BRCA1/2 mutation carriers in Germany: study protocol for a randomised controlled parallel-group trial." Trials 23(1): 157.
	Background: Women with BRCA1/2 mutations have a higher risk of developing breast and ovarian cancer compared to women of the general population. Various preventive options are available to deal with the increased risk of developing cancer. These include intensified breast cancer screening and risk-reducing bilateral mastectomy and salpingo-oophorectomy. The choice of a preventive option can lead to increased decisional conflict. To support these women in their decision-making process, two evidence-based decision aids were developed in an upstream research process and adapted to the German healthcare context. These will be evaluated within a randomised controlled trial (RCT) in terms of their effects on decision-making, women's level of information and psychological outcome variables.; Methods: A sample of 310 women carrying BRCA1/2 mutations (A) without a history of cancer or (B) with a history of unilateral breast cancer who have received post-test genetic counselling will be enrolled. Upon study consent, women will be randomly assigned to either the intervention or the control group. All participants will receive standard care including a physician's letter summarising the counselling content. After baseline data collection (t0), the intervention group receives the respective decision aid while the control group receives standard care only. The primary outcome variable assessed at a 3-month follow-up (t1) is the change of extent in decisional conflict (measured with the Decisional Conflict Scale). Secondary outcome variables comprise the stage of decision-making, self-reported symptoms of anxiety, depression and stress due to the genetic test result, and knowledge regarding cancer risks and preventive options. At t1, the extent of preparation for decision-making and acceptability of the decision aids will also be examined. Another secondary outcome variable assessed at 6-month follow-up (t2) is the extent of decision regret.; Discussion: These will be the first decision aids available for BRCA1/2 mutation carriers in Germany to be evaluated regarding their effectiveness and acceptability in clinical use within an RCT. Subsequently, they are to be integrated into the care concept of the centres of the German Consortium for Hereditary Breast and Ovarian Cancer and the affiliated breast centres. TRIAL REGISTRATION {2A}: DRKS DRKS00015823 . Retrospectively registered on 14 June 2019. (© 2022. The Author(s).)

Kawabata, H., et al. (2022). "Correction to: intravenous ferric derisomaltose versus saccharated ferric oxide for iron deficiency anemia associated with menorrhagia: a randomized, open-label, active-controlled, noninferiority study." International Journal of Hematology 116(6): 976‐977.
	In the original publication of the article, the Fig. 3 was published with errors. The correct Fig. 3 is given in this correction.

Kawamura, K. and Y. Sato (2023). "Effectiveness of supplement ingredients on infertility treatment in advanced aged women." The Journal of Obstetrics and Gynaecology Research 49(8): 2015-2022.
	Aim: Despite the remarkable progress made in reproductive medical technology in recent years, there has been no improvement in overall pregnancy and birth rates for the rising number of infertile patients. This is thought to be due to the increase in intractable infertility with ovarian dysfunction, as the desired age of pregnancy has increased for women. The aim of this article is to review preclinical studies that used laboratory animals and other tools to examine the effectiveness of diverse supplement ingredients on age-related ovarian dysfunction as well as recent human clinical trials using supplement ingredients.; Method: We summarized the articles discussing the effectiveness of supplement ingredients on infertility treatment in advanced-aged women by searching PubMed, Cochrane, EMBASE, and Google Scholar databases until December 2022.; Results: Supplements are relatively inexpensive and convenient for patients, as they can be purchased at the will of the individual and from among multiple options. Although supplements have been demonstrated to have certain effects in animal studies, evidence of their effectiveness in humans is either lacking or insufficient for reaching a definite conclusion. This may be due to the lack of standardized diagnostic criteria for ovarian dysfunction and poor responders, unclear optimal dosages and duration of supplement intake, and well-designed randomized clinical trials.; Conclusion: Additional lines of evidence on the effectiveness of supplements in patients with ovarian dysfunction at an older age need to be accumulated in the future. (© 2023 Japan Society of Obstetrics and Gynecology.)

Kay, N. (2021). "Oxytocin receptor antagonists in in-vitro fertilisation: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Kazakova, S. N., et al. (2022). "LYPIDOME ANALYSIS OF CERVICOVAGIANL FLUID IN PATIENTS WITH VULVOVAGINAL ATROPHY UNDER EXPOSURE TO DYNAMIC QUADRIPOLAR RADIOFREQUENCY." Akusherstvo i Ginekologiya (Russian Federation) 2022(12): 132-138.
	Objective: To study specific features of cervicovaginal fluid lipidome in patients with vulvovaginal atrophy (VVA) in postmenopause under exposure to dynamic quadripolar radiofrequency (DQRF). Material(s) and Method(s): The study included 60patients aged 46- 65 years (the mean age 54.8(5.1) years) with the symptoms of VVA. Ail patients underwent treatment: dynamic quadripolar radiofrequency was used in the area of vulva and vagina in group 1 (4 procedures with 2-week intervals); DQRF with radioporation technique with application of cream containing 0.5 mg estriol was used in group 2(4 procedures with 2-week intervals); and local hormonal treatment with cream containing 0.5 mg estriol was used in group 3 (8 weeks of treatment). Lipid extraction from cervicovaginal fluid was performed using modified Folch method at two-time points - before and 1 month after treatment. Result(s): Lipidome analysis compared 3 groups of samples of cervicovaginal fluid- in 40 patients before and after exposure to DQRF and in 20 patients before and after treatment with local estrogens according to treatment regimen. 6 compounds were isolated. Their levels were statistically significantly higher in the group of patients who were exposed only to radiofrequency - Anandamide (18:2, n-6), DG 18:0/18:0/0:0, DG 18:0/16: 0/0:0, LTB4-dimethylamide, N-hydroxy arachidonoilamine, Virodhamin. The levels of Anandamide (18:2, n-6), LTB4-dimethylamide, N-hydroxy arachidonoilamine and Virodhamin were statistically significantly lower in patients who were exposed to radiofrequency in combination with estrogens for treatment of VVA in postmenopause. Conclusion(s): This article describes an innovative approach to alternative treatment of women with VVA in postmenopause using DQRF. The results of lipidome analysis of cervicovaginal fluid after exposture to DQRF are published for the first time. Further study and research in the field of high energy methods for VVA treatment are necessary to assess the effectiveness and safety of long term radio wave exposure.Copyright © A group of authors, 2022.

Kazemi, A., et al. (2020). "Effect of probiotic and synbiotic supplementation on inflammatory markers in health and disease status: A systematic review and meta-analysis of clinical trials." Clinical nutrition (Edinburgh, Scotland) 39(3): 789-819.
	The current systematic review and meta-analysis investigated the effect of probiotic/synbiotic on a wide range of inflammatory and anti-inflammatory markers in healthy and various disease conditions. PubMed, SCOPUS and Web of Science databases were searched. All clinical trials which investigated the effect of oral administration of probiotic or synbiotic on inflammatory markers (C-reactive protein (CRP), interleukin (IL) 1β, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF) α, interferon (IFN) γ and transforming growth factor (TGF) β) for more than one week with concurrent control groups were included. One-hundred sixty seven publications was analysed. Results were as follows: CRP decreased in healthy, metabolic disorders, inflammatory bowel disease (IBD), arthritis and critically ill condition but not in renal failure. IL-1B: no change in healthy subjects and arthritis. TNF-α: decreased in healthy, fatty liver, IBD and hepatic cirrhosis, no change in diabetes, metabolic syndrome (MS) + PCOS (polycystic ovary syndrome) and arthritis. IL-6: no change in healthy, metabolic disorders and arthritis, increased in cirrhosis and renal failure, decreased in PCOS + MS. IL-10: no change in healthy, IBD and metabolic disorders, increased in arthritis. IL-4, IL-8, IL-12, IFN-g and TGF-b: no change in healthy subjects. In conclusion, probiotic/synbiotic decreased some of the inflammatory markers. The intervention was most effective in CRP and TNF-α reduction in healthy or disease state. Moreover, the intervention decreased inflammation most effectively in the following disease conditions, respectively: IBD, arthritis, fatty liver. PROSPERO REGISTRATION NUMBER: CRD42018088688. (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Kazeminasab, F., et al. (2023). "The effect of exercise training on metabolic factors in women with polycystic ovary syndrome: A systematic review and meta-analysis." Iranian Journal of Obstetrics, Gynecology and Infertility 26(6): 94-113.
	Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, which is associated with insulin resistance. The present systematic review and meta-analysis study was conducted with aim to investigate the effect of exercise training on metabolic factors in women with PCOS. Method(s): In this study, a systematic search was conducted in PubMed, Web of Science, SID, Magiran, and Google Scholar databases for English and Persian articles published until September 2022. Meta-analysis was performed to investigate the impact of exercise training on fasting blood glucose, insulin, insulin resistance index (HOMA-IR), fat percentage and body fat mass in women with PCOS. Standardized mean differences (SMD) or weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using random effect model. Also, I2 test was used to determine heterogeneity, and funnel plot and Egger test were used to evaluate publication bias. Result(s): Exercise training caused a significant decrease in insulin [SMD=-0.47, -0.79 to -0.15, P=0.004], HOMA-IR [WMD=-0.57, -1.02 to -0.12, P=0.01), and body fat percentage [WMD=-1.89, -3.36 to -0.42, P=0.01] in women with PCOS; but exercise did not change fasting glucose [WMD=0.65, -2.17 to 3.47, P=0.65] and body fat mass [WMD=-1.58, -3.88 to 0.7, P=0.17]. Conclusion(s): Exercise reduces body fat percentage, fasting insulin, and insulin resistance in PCOS patients. It is noteworthy that both types of aerobic and resistance training reduce fasting insulin in these patients, but the impact of resistance training is greater than aerobic exercise. Therefore, exercise is recommended as a non-drug solution to improve body composition, reduce insulin resistance and prevent diabetes for women with PCOS.Copyright © 2023, Mashhad University of Medical Sciences. All rights reserved.

Kazeminia, M., et al. (2022). "The effect of exercise on anti-Mullerian hormone levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis." Middle East Fertility Society Journal 27(1): 31.
	Background: Polycystic ovary syndrome (PCOS) is considered as the most common endocrinopathy among women of childbearing age and the most important cause of anovulatory infertility. The present study aimed to estimate the pooled effect of exercise on anti-Mullerian hormone (AMH) levels in PCOS women using systematic review and meta-analysis. Main body: The present study was conducted according to the PRISMA guidelines from 2011 to October 2021. All published studies, which met the inclusion criteria, were searched in SID, MagIran, Embase, PubMed, Scopus, Web of Science (WoS) databases, and Google Scholar motor engine using related MeSH/Emtree terms, which were combined with free text word. Finally, 12 articles were included in the meta-analysis. As a result of the combination of the studies, after exercise, AMH level in the intervention group significantly decreased up to 0.517 +/- 0.169 more than that in the control group (P 0.05). The results of subgroup analysis demonstrated that the effect of resistance training for 16 weeks was higher on women with body mass index (BMI) (>= 25 kg/m2) and AMH (>= 10 ng/mL) before the intervention. GRADEpro software was used to grade the level of evidence. Conclusion(s): This systematic review and meta-analysis showed that either strength exercise or aerobic exercise decrease the AMH level in PCOS women. It seems more duration of the exercise has a more potential advantage to reduce the AMH levels in women with PCOS. Although the results graded by very low-quality evidence, it is recommended to include exercise in the treatment programs of PCOS patients.Copyright © 2022, The Author(s).

Kazempour, R., et al. (2023). "Effect of Selenium Supplementation on Biochemical Markers of Women with Polycystic Ovarian Syndrome: A Systematic Review." Preventive nutrition and food science 28(2): 121-133.
	Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder among fertile women and may be induced by nutritional deficiencies. In this study, we assess the impact of selenium supplementation (SS) on biochemical markers in women with PCOS. To gather relevant literature, we searched the Web of Science, Cochrane Library, Scopus, Embase, and MEDLINE databases from inception up to July 24, 2022. Subsequently, we included all published full-text randomized clinical trials examining the effects of SS versus placebo on biochemical changes in women with PCOS. Review Manager 5.3 was used to collect and analyze data and assess the risk of bias. Seven articles, comprising 413 women, were ultimately involved in the study. According to the results, SS could increase the level of quantitative insulin sensitivity check index [standardized mean difference (SMD)=0.34, 95% confidence interval (CI)=0.04∼0.65], total antioxidant capacity (SMD=0.89 mmol/L, 95% CI=0.52∼1.26), and glutathione (SMD=1.00 μmol/L, 95% CI=0.22∼1.78). Conversely, SS could decrease triglyceride, cholesterol, fasting plasma glucose, insulin, and the homeostasis model of assessment-insulin resistance levels compared with the placebo. Furthermore, there were no significant differences regarding sex hormone-binding globulin level, testosterone level, malondialdehyde, and body mass index between the two groups. In addition, the results suggest that SS improves biochemical markers in women with PCOS and thus is recommended for treating biochemical disorders among these women in addition to standard treatment.; Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest. (Copyright © 2023 by The Korean Society of Food Science and Nutrition. All rights Reserved.)

Kct (2021). "Clinical trial for the evaluation of the efficacy and safety of isoflavone on menopausal symptoms." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Dietary Supplement : The soybean extract complex group took one tablet two times a day (Soybean extract complex 190mg/day) for 12 weeks. The placebo group was provided with identically shaped tablet. The placebo was also taken two times a day for 12 weeks. CONDITION: Diseases of The genitoruinary system PRIMARY OUTCOME: Changes of Modified KMI scores SECONDARY OUTCOME: Changes of Modified KMI subcategories score, ALP, OC, and urine‐NTx INCLUSION CRITERIA: 1) Postmenopausal women aged between 40 and 60 years. 2) Modified kupperman index > 20

Kct (2021). "Cortisol secretory pattern between deep neuromuscular block and moderate neuromuscular block in Total laparoscopic hysterectomy patient under anesthesia with total intravenous anesthesia (TIVA) using propofol and remifentanil." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : The patients were assigned to group D (deep neuromuscular blockade: target train‐of‐four (blockade: target) 0 and post tetanic count = 1) or group M (moderate neuromuscular blockade: target TOF 1‐3). At induction, patients in each group were administered rocuronium intravenously (0.6 mg/kg [moderate neuromuscular blockade] to 1.2 mg/kg [deep neuromuscular blockade]). During surgery, each group were administered rocuronium continuously with monitoring of TOF(the train‐of‐four (TOF) 1‐3 in patients with moderate neuromuscular blockade and TOF count of 0 and posttetanic count = 1 in patients with deep neuromuscular blockade ). CONDITION: Neoplasms PRIMARY OUTCOME: adrenocorticotropic hormone(ACTH) cortisol serum glucose SECONDARY OUTCOME: hospital stay fentanyl dose postoperative pain NRS (Numeric rating scale) sarisfaction of surgeon INCLUSION CRITERIA: ASA class 1 and 2, aged 20 to 75 years old, and scheduled for laparoscopic gynecological surgery were included in this study.

Kct (2021). "Development of lifestyle modification program using ICT for obese polycystic ovary syndrome patients." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Others(Lifestyle modification program using ICT) : Experimental group ‐ We provide lifestyle modification programs using ICT for 12 weeks. ‐ Every day, participants report lifestyle (diet, steps per day, body weight, height) and gynecological symptoms (hirsutism, acne, menstrual cycle). ‐ Feedback is provided twice a week via SNS or phone. ‐ Participants visit the center once a month for consultation. Control group ‐ Usual care ‐ Provide Leaflet CONDITION: Diseases of The genitoruinary system PRIMARY OUTCOME: Physical indicators (weight, blood pressure) Productivity indicators (menstrual cycle, pregnancy status) SECONDARY OUTCOME: Acne (Global Acne Grading System) App Usability and Program Satisfaction Depression (K‐CESD) Hirsutism (Ferriman‐Gallwey Score) Hormone indicators (Basal hormone(LH, FSH, E2), Androgenic hormone (TT, SHBG, DHEAS)) Insulin resistance indicators (glucose, insulin) INCLUSION CRITERIA: 1. Patients with obesity polycystic ovarian syndrome (BMI=23) 2. Those who can use computers and cell phones 3. A person who understands and agrees to participate in the research

Kct (2021). "The effect of 5-hydroxytryptamine-3 receptor antagonists on opioid-induced hypotension or bradycardia at anesthesia induction." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : In the intervention group, 0.3 mg/2 ml of Nasea (ramosetron 0.3 mg/2 ml) mixed with 100 ml of saline solution is administered intravenously at the anesthesia induction. In the control group, the same dose of Nasea 0.3 mg/2ml (ramosetron 0.3 mg/2ml) mixed with 100 mL of saline solution is administered intravenously at the end of anesthesia. The difference between the intervention group and the control group is at the time of administration of Ramosetron. CONDITION: Neoplasms PRIMARY OUTCOME: Blood pressure SECONDARY OUTCOME: Postoperative nausea and vomiting INCLUSION CRITERIA: ASA class I adult patient who undergoing laparoscopic gynecological surgery

Kct (2021). "The effect of a single shot of intrathecal morphine on the use of postoperative analgesics after non laparoscopic surgery of gynecologic oncology." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : ? All subjects get informed consent to the patient and guardian the day before surgery. At this time, the degree of pain and neurological tests are performed as a basic test, and the patient's health status is assessed through the Quality of Recovery 15K (hereinafter referred to as QoR‐15K) questionnaire. ? All patients are placed in the lateral position after full monitoring (EKG, NIBP, SpO2) according to the usual anesthesia procedure after entering the operation room. ? In the test group, sterilize with 2% chlorhexidine at L3/4 level at least 4 times, perform local anesthesia with lidocaine, and then use a 27G pencil‐point needle to access intrathecal space and administer 200mcg (0.2mL) of morphine mixed with 1.8 mL of CSF ( total 2mL). ? In the control group, sterilize with 2% chlorhexidine at the L3/4 level at least 4 times, and then perform sham procedure poking the same level twice using the blunt tip of the stylet of the 27G pencil‐point needle. ? After that, an independent anesthesiologist follows the usual procedure and proceeds without any special intervention. Currently, propofol and remifentanil are used in our gynecological cancer surgery to induce anesthesia with vestibular anesthesia and maintain anesthesia with the aim of Bispectral Index 40‐60. In all groups, at the start of suture, IV‐PCA (intravenous autologous pain control device) is connected to the peripheral venous tube and administration is started, and no additional analgesics are administered. In IV‐PCA, a drug with a fentanyl concentration of 20 mcg/ml is set at a basal injection amount of 10 mcg/h, a single injection amount of 10 mcg, and a closing time of 15 minutes. Total anesthesia time, operation time, drugs used during anesthesia, and vital signs are collected through medical re CONDITION: Neoplasms PRIMARY OUTCOME: The cumulative dose of opioid SECONDARY OUTCOME: Cumulative dose of opioid and NRS at each time point, time of first opioid use, recovery related indicators (flatus, normal diet, first ambulation, foley catheter removal, recovery evaluation index: QoR‐15K), side effects of opioid INCLUSION CRITERIA: (1) patients undergoing elective laparotomic gynecologic surgery (2) ASA classification I ‐ III adult patient

Kct (2021). "Effect of Ketorolac versus Nefopam after Laparoscopic Supracervical Hysterectomy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : Patients were randomly divided into a group using Ketorolac and Nefopam. At the end of surgery, in the Ketorolac group, 1000 µg of fentanyl, 150 mg of ketorolac, and 0.6 mg of ramosetron were mixed with physiological saline to make a total amount of 100 ml. Make the total amount to 100 ml. In both groups, the basic dose was set at 4 ml/hr, a single injection volume of 2 ml, and the closing interval was 5 minutes. If the patient presses the button due to pain, the basic dose is increased by 0.5 ml per hour, and the button is not pressed for 20 minutes. In this case, the basic dose is set to decrease by 0.5 ml per hour. The maximum and minimum hourly doses are 6 ml/hr, 2 ml/hr up to 2 hours after surgery, 5 ml/hr, 1 ml/hr from 2 hours to 6 hours after surgery, and 6 hours after surgery. 4 ml/hr, set to 0.5 ml/hr. CONDITION: Neoplasms PRIMARY OUTCOME: postoperative nausea and vomiting SECONDARY OUTCOME: the quantity of analgesics used by each patient, the administration of additional analgesics, background infusion rate, Numerical rating scale, the sedation level, and other side effects INCLUSION CRITERIA: The adult patients were between the ages of 20 and 65 years, with American Society of Anesthesiologists (ASA) physical status of 1 or 2, and had requested postoperative IV‐PCA for laparoscopic gynecologic surgery scheduled to be performed at our hospital.

Kct (2022). "Acupuncture for the treatment of hot flashes in patients with breast cancer receiving antiestrogen therapy." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Medical Device : In the acupuncture group, participants received acupuncture treatment 3 times a week for 4 consecutive weeks. During the study period, participants in the control group received the usual care for breast cancer without any treatment for hot flashes. A total of 8 needles are used in each acupuncture session. The acupuncture needles are sterile, disposable stainless steel needles (F 0.2 × 30 mm; Dongbang Acupuncture Inc., Chungcheongnam‐do, Korea). The acupuncture treatment time was 25 ± 5 minutes in each session. After swabbing the skin with an alcohol prep pad, acupuncture is performed. The acupuncture needles are inserted 10‐20 mm deep into the skin of the selected acupuncture points and are gently manipulated manually to obtain De Qi.24‐26 Ten minutes after initial insertion of the needles, the acupuncturist manipulated the needles using techniques including rotating, lifting and thrusting without evoking needle sensation to maintain the intensity of the De Qi (obtaining qi) sensations. CONDITION: Neoplasms PRIMARY OUTCOME: severity of hot flashes ? visual analogue scale (VAS) ? total hot flash score SECONDARY OUTCOME: QoL of the participants: the EORTC QLQ‐C30 version 3.0 questionnaire and the EORTC QLQ‐BR23 INCLUSION CRITERIA: ? moderate or severe hot flashes symptoms according to the definition of the Food and Drug Administration ? an average of 3 or more hot flashes per week during the 1‐week period before study entry ? voluntary participation ? follow‐up for the duration of the study ? cessation of HRT or other pharmacologic or alternative treatments for hot flashes at least 4 weeks before the trial, if such treatments were used

Kct (2022). "Comparison of postoperative nausea and vomiting accoring to manual and target controlled infusion of remifentanil in gynecological patients undergoing pelviscopic surgery - Randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Others(Continuous infusion methods of Remifentanil) : The study was conducted by dividing the continuous infusion methods of remifentanil during surgery into two types: manual infusion (manual injection by determining the infusion rate per hour) and target controlled infusion (using a program that calculates the target concentration in advance using a pharmacological formula). CONDITION: Neoplasms PRIMARY OUTCOME: incidence of post operative nausea and vomiting SECONDARY OUTCOME: post operative pain (NRS) INCLUSION CRITERIA: Patients scheduled for elective gynecological surgery using pelviscopy under general anesthesia

Kct (2022). "The effect of erector spinae plane block on the use of postoperative analgesics after open gynecologic oncology surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Procedure/Surgery : ? All subjects get informed consent to the patient and guardian the day before surgery. At this time, the degree of pain and neurological tests are performed as a basic test, and the patient's health status is assessed through the Quality of Recovery 15K (hereinafter referred to as QoR‐15K) questionnaire. ? All patients are placed in the lateral position after full monitoring (EKG, NIBP, SpO2) according to the usual anesthesia procedure after entering the operation room. ? In the experimental group, switch patient's position to lateral decubitus after induction of aneshtesia. Sterilize more than 4 times with 2% chlorhexidine at T9 level, locate the 22G needle between erector spinae muscle and transverse process of T9 under ultrasound confirmation. Inject local anesthetics (0.5% ropivacaine 20ml) in both side. ? In the control group, no additional intervention is performed. ? After that, an independent anesthesiologist follows the usual procedure and proceeds without any special intervention. Currently, propofol and remifentanil are used in our gynecological cancer surgery to induce anesthesia with vestibular anesthesia and maintain anesthesia with the aim of Bispectral Index 40‐60. In all groups, at the start of suture, IV‐PCA (intravenous autologous pain control device) is connected to the peripheral venous tube and administration is started, and no additional analgesics are administered. In IV‐PCA, a drug with a fentanyl concentration of 20 mcg/ml is set at a basal injection amount of 10 mcg/h, a single injection amount of 10 mcg, and a closing time of 15 minutes. Total anesthesia time, operation time, drugs used during anesthesia, and vital signs are collected through medical records. ? After the end of anesthesia, the degree of pain immediately CONDITION: Neoplasms PRIMARY OUTCOME: opioid cumulative dose SECONDARY OUTCOME: Cumulative dose of opioid and NRS at each time point, time of first opioid use, recovery related indicators (flatus, normal diet, first ambulation, foley catheter removal, recovery evaluation index: QoR‐15K), side effects of opioid INCLUSION CRITERIA: (1) patients undergoing elective open gynecologic surgery (2) ASA classification I ‐ III adult patient

Kct (2022). "The effect of pilates exercise on menstrual pain." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Procedure/Surgery : The Pilates group has a total of 24 Pilates sessions for 12 weeks. The Pilates program is conducted twice a week for 50 minutes per session and consisted of a series of mat exercises designed to relax and strengthen back, abdominal, and pelvic muscles. The wait‐list control group receives no treatment during 12 weeks and then has a total of 24 Pilates sessions for 12 weeks. CONDITION: Diseases of the genitourinary system PRIMARY OUTCOME: Menstrual pain intensity, Menstrual symptom severity and frequency SECONDARY OUTCOME: Shoulder and pelvic balance, back flexibility, quality of sleep, and psychological variables INCLUSION CRITERIA: ‐19‐39 years of age ‐Primary dysmenorrhea

Kct (2022). "Effect of use of Nasea (ramosetron) and dexamethasone on postoperative recovery in surgery without patient controlled analgesia (PCA) after surgery; Randomized Controlled Trials." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : # Treatment group: Dexamethasone 5 mg (0.15 mg/kg) iv after induction of anesthesia, and Ramosetron 0.3 mg (6 µg/kg) iv before the end of surgery. # Active Control group: Ramosetron 0.3 mg (6 µg/kg) iv before the end of surgery. CONDITION: Neoplasms PRIMARY OUTCOME: verbal numerical rating scale (VNRS) was used to evaluate the patient's nausea and vomiting at 6, 12, and 24 hours after surgery. SECONDARY OUTCOME: Pain control (VAS) between ramosetron versus ramosetron + dexamethasone: reduced VAS compared to baseline PONV incidence by risk factor score (age, underlying disease, gender, previous history of nausea and vomiting, medications taken, etc.) PONV incidence by surgery Side effects after drug injection Use of the frequency of rescue drug with ramosetron and ramosetron + dexamethasone INCLUSION CRITERIA: ? Patients 19 years of age or older ? Patients managed without Patient Controlled Analgesia (PCA) after surgery ? Type of surgery: general surgery, gynecological surgery, neuro‐orthopedic surgery, plastic surgery, otolaryngology surgery ? Patient who signs informed consent (ICF)

Kct (2022). "Effectiveness of Routine Intensive CA125 Monitoring in Ovarian Cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: CONDITION: Neoplasms PRIMARY OUTCOME: Rate of early recurrence for which secondary tumor reduction surgery is possible SECONDARY OUTCOME: Difference between PFS and PFS2, Prediction accuracy of R0 success rate of secondary tumor reduction surgery, Prognostic factors when performing surgery after secondary tumor reduction, Diagnostic accuracy of CA125 EPD diagnostic criteria, Diagnostic accuracy of imaging tests in the early progression of ovarian cancer INCLUSION CRITERIA: 1. Histologically confirmed advanced (FIGO III‐IV) ovarian cancer, fallopian tube cancer, and primary peritoneal cancer patients 2. Serum CA125 concentration of 2x35 U/ml or higher before initiation of treatment 3. Patients with complete remission after primary chemotherapy (excluding maintenance therapy) 4. Serum CA125 concentration below normal (upper normal level (UNL) 35U/ml) 5. Patients 18 years of age or older who gave written informed consent to this trial

Kct (2022). "Effects of auricular acupressure on menopausal symptoms." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Others(auricular acupressure) : For this study, auricular acupressure was administered to the experimental and control groups for eight weeks. The researcher assessed the general condition of the subjects’ ears before auricular acupressure was applied; one ear per participant was then disinfected with a 70% alcohol wipe, and the researcher noted any abnormal findings regarding the ears. A sticker with a vaccaria seed, which is easy to apply and effective in meridian flow, was used for the treatment. The sticker was pressed to the acupoints for a few seconds at an intensity that was enough for the subjects to feel pain. The stickers were maintained for five days, and the subjects were instructed to directly remove the stickers on the sixth day of the treatment, after which they had a rest period of two days. This method was repeated once a week for eight weeks. If a sticker fell off before the fifth day after attachment, the subjects contacted the researcher in order to reattach the stickers. After one week of the treatment, the researcher revisited the subjects to check the integrity of the skin where the seeds were applied. Since excessive pressure might have been applied, the new stickers were applied to the other ear in the same manner. In order to reinforce the effect of the auricular acupressure, the subjects were instructed to press the areas applied with stickers three times a day and one hour before going to sleep to the extent that it was slightly painful. The auricular acupressure was applied for eight weeks by applying pressure to the five acupoints that are known to be effective in improving menopause symptom, stress and sleep quality. In the control group, auricular acupressure was applied to five acupoints that were not related to menopause symptom, stress CONDITION: Diseases of the genitourinary system PRIMARY OUTCOME: Menopause Rating Scale (MRS) SECONDARY OUTCOME: actigraphy Brain waves(Neuro‐feedback System) Heart rate variability Perceived Stress Scale(PSS) PSQI (Pittsburgh Sleep Quality Index) INCLUSION CRITERIA: ‐ Women over 40 and under 64 ‐ Women with menopause within 10 years ‐ Those who have naturally stopped menstruating for more than 1 year from the date of their last menstruation ‐ Women with a score of 5 or higher on the Menopause Symptom Scale (MRS) ‐ Women with a quality of sleep (PSQI) score of >5

Kct (2022). "Evaluation of the effectiveness of soybean lettuce mixture powder for improving menopausal symptoms." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Dietary Supplement : Participants are randomly offered to a soybean lettuce mixed extract or placebo for 1 tablet at a time, 4 times a day (after each meal and bed). When a participant starts to take, take a total of four weeks. There is no dosing and treatment difference between the placebo group and the experimental group. CONDITION: Diseases of the genitourinary system PRIMARY OUTCOME: Kupperman index SECONDARY OUTCOME: total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglyceride (TG), non‐HDL‐cholesterol (NonHDL‐C), ALT, AST, gamma ‐glutamyl transferase, BUN, creatinine, glucose, and high sensitivity C‐reactive protein, serum thyroid‐stimulating hormone (TSH), estradiol, Follicle‐stimulating hormone (FSH) levels INCLUSION CRITERIA: Adult women aged 45 or older and under 70 years old, who have reached menopause, must have menopause syndrome, and have a Kupperman index of 15 or higher, can participate.

Kct (2022). "Validation of the effectiveness of music therapy for improving mood and psychosomatic symptoms in menopausal women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Others(music therapy program) : The experimental group participates in music therapy once a week for 8 weeks and the control group participates in cognitive behavioral therapy once a week for 8 weeks. Both programs consist of a total of eight sessions, and each session lasts for 60 minutes. CONDITION: Diseases of the genitourinary system PRIMARY OUTCOME: World health organization quality of life assessment instrument (WHOQOL‐BREF) SECONDARY OUTCOME: Generalized Anxiety Disorder‐7 Kupperman Index Menopause Emotional Symptoms Scale Menopause Rating Scale Patient Health Questionnaire‐15 Patient Health Questionnaire‐9 Subjective Memory Complaints Questionnaire INCLUSION CRITERIA: 1. menopausal (the period from the onset of irregular menstrual cycles to one year after the last menstruation) women 2. 40 to 60 years old 3. Kupperman inde Xto assess the severity of menopause symptoms = 10

Kct (2023). "Effect of the Korea Integrated Support Program for Infertile Women (KISPIW): a Pilot and Feasibility Randomized Controlled Trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Behavioral : At the time of development, si Xexperts (two obstetrics and gynecology physicians, one family medicine specialist, a health policy professor, a psychological counselor, and a nutritionist each) were consulted, who verified the program’s feasibility. During the eight‐week of the program, the experimental group was participated in the following sessions. First, education session was held every Monday for 60 minutes. Second, exercise and eating habits sessions were held every Wednesday; each session was held for 30 minutes. Third, mental health management sessions were held every Friday; each session was held for 30 minutes. Regarding the group sessions, a total of two sessions were held on the 4th and the 8th Wednesday for 40 minutes each session. The control group only had the same two group sessions on the 4th and the 8th Thursday. CONDITION: Diseases of the genitourinary system PRIMARY OUTCOME: depression health promotion behaviors quality of life self efficacy self esteem social support stress SECONDARY OUTCOME: Feasibility INCLUSION CRITERIA: The inclusion criteria for selecting participants are as follows: (i) married women over the age of 19, (ii) those diagnosed with female infertility (ICD‐10: N97, female infertility) by a physician, (iii) those who have no experience of childbirth, (iv) those who have not participated in the healing program, and (v) those who could read and understand the researcher's instructions and signed the consent form.

Kct (2023). "Effects of phytoncide on physiological variables, quality of life, and chronic disease morbidity in cancer survivors." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Behavioral : In this study, phytoncide essential oil, Korean hinoki cypress (Chamaecyparis obtusa), was selected for olfactory stimulation. The aroma scent diffusion method was used for phytoncide inhalation in this study. An oil burner (Good Earth Lab., Seoul, Korea) made of cypress wood with a height of 125 mm, a top width of 70 mm, and a bottom width of 70 mm was used. The main essential oil components extracted from cypress trees were terpenes that mainly consisted of monoterpene (C10H16) and sesquiterpene (C15H24). Three to five drops of phytoncide essential oil were dropped on the burner to allow the wood to absorb the natural scent and emit a subtle scent. To maintain the degree of scent diffusion, the temperature of the closed laboratory space of about 66 m² was maintained at 25‐26? and the humidity was maintained at about 50‐60%. Whether an odorant occurs naturally or is produced synthetically, it may be unsafe, particularly in high concentrations. Many fragrances may also be potent allergens. For these reasons, the phytoncide aroma emitted in this study was less than the recommended amount. The phytoncide group (PTG) lay on the mattress for 60 minutes a day, 5 days a week, and smelled the scent of phytoncide. The PTG only felt that the fragrance was good, but did not know what effect it had. The control group was allowed to lie down on the mattress for 60 min and take a rest in a different place where no phytoncide oil treatment was given. CONDITION: Factors influencing health status and contact with health services PRIMARY OUTCOME: Stress scale, Body composition, Autonomic nervous system, Stress hormones, NK cells SECONDARY OUTCOME: Dietary method, Physical activity amount INCLUSION CRITERIA: The participants of this study were gynecological cancer survivors who were diagnosed with cervical cancer, ovarian cancer, or breast cancer between January 2016 and December 2020 and underwent surgery, primary cytoreductive surgery, radiation therapy, or chemotherapy, with a survival rate of less than ?ve years.

Kct (2023). "Effects of self-mobilization for the pelvic joint and pelvic floor muscles and pilates core exercise on premenstrual syndrome, menstrual pain, and spinal alignment in adult women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Others(Exercise) : 3 times a week, for a total of 3 months, watch video materials in a personal space and conduct a 20‐30 minute program twice a day as shown below. <Self‐mobilization group> It consists of Pilates breathing, pelvic floor muscle soft tissue mobilization, pelvic mobilization exercise, pelvic tilt exercise, pubic symphysis mobilization exercise, sciatic nerve mobilization exercise, cat exercise, and Pilates breathing. <Pilates core exercise group> The exercise program is composed in the order of Pilates breathing (preparation exercise), bridge, plank, swan, baby pose, plank, and Pilates breathing (cooling‐up exercise). <Mixed exercise group> Perform the above Pilates core exercise and self‐mobility technique together. CONDITION: Diseases of the genitourinary system PRIMARY OUTCOME: Lumbar lordosis angle, lumbar 4/5 angle, angle between lumbar 5 and sacrum, sacral angle, sacral inclination angle Menstrual Distress Questionnaire: MDQ pain intensity of menstrual cramps SECONDARY OUTCOME: Functional leg length test INCLUSION CRITERIA: 1) Adult women in their 20s and 30s with premenstrual syndrome and dysmenorrhea 2) If you can understand the participation in the research and can participate in the research voluntarily

Kct (2023). "A prospective randomized controlled trial evaluating the safety and efficacy of patient blood management program in patients with gynecologic cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : Design: A prospective randomized controlled trial Treatment of patients for each carcinoma is carried out according to KSGO’s treatment guideline 1. PBM on Surgical treatment (1) before surgery (within 2‐6 weeks before surgery) [Investigator group treatment] ‐ 7 = Hb < 12 g/dL : ferric carboxymaltose 1000mg [Control group treatment] ‐ 8 = Hb < 10 g/dL: pRBC 1 pack transfusion ‐ Hb < 8 g/dL: pRBC 2 packs transfusion * Use of oral iron supplements, EPO, in control patients is permitted. (no IV iron supplements) (2) during surgery [Investigator group treatment] ‐ In case of hemodynamically unstable, transfusion according to the judgment of the operating surgeon and anesthesiologist [Control group treatment] ‐ In case of hemodynamically unstable, transfusion according to the judgment of the operating surgeon and anesthesiologist (3) after surgery (POD #1) [Investigator group treatment] ‐ 7 = Hb < 12 g/dL : ferric carboxymaltose 1000mg ‐ Hb <7 g/dL : pRBC 2 packs transfusion [Control group treatment] ‐ 8 = Hb < 10 g/dL: pRBC 1 pack transfusion ‐ Hb < 8 g/dL: pRBC 2 packs transfusion * Use of oral iron supplements, EPO, in control patients is permitted. (no IV iron supplements) 2‐1. PBM on radiation or concurrent chemotherapy treatment after surgery Blood tests: the day of mock therapy and every 3weeks (visit window ±1w) during (CC)RT and 3 weeks after the end of treatment (visit window ±1w) [Investigator group treatment] ‐ 7 = Hb < 12 g/dL : ferric carboxymaltose 1000mg IV ‐ Hb < 7 g/dL: pRBC 2 packs transfusion * If anemia correction is required during other treatment visits, only Ferric carboxymaltose 1000 mg IV is permitted. Do not allow the use of oral iron supplements. [Control group treatment] ‐ 8 = Hb < 10 : pRBC 1 pack transfusion ‐ Hb < 8 : p CONDITION: Neoplasms PRIMARY OUTCOME: Transfusion rate within 3 weeks after surgery SECONDARY OUTCOME: Comparison of hemoglobin differences between the groups Cost‐effectiveness differences of between the groups Differences in quality of life of between the groups Frequency and delay period of treatment delay due to anemia before adjuvant therapy between the groups Frequency of anemia and blood transfusion before adjuvant therapy between the groups Treatment related adverse events INCLUSION CRITERIA: 1) Women aged 20‐80 years 2) Untreated, histologically diagnosed cervical cancer, endometrial cancer, and ovarian cancer (including cases diagnosed by imaging without biopsy in the case of ovarian cancer) 3) Patients with ECOG performance status 0‐2 4) Patients with ASA PS 1‐2 5) Preoperative Hgb = 7 g/dL 6) Patients who are scheduled for preoperative iron panel test (serum ferritin, iron, TIBC) 7) In case of showing proper organ function WBC = 3,000/mm3 Platelets = 100,000/mm3 Creatinine = 2.0 mg/dL Bilirubin = 1.5 Xinstitutional upper limit normal SGOT, SGPT, and ALP = 3 Xinstitutional upper limit normal 8) Patient who voluntarily signed the informed consent form

Kct (2023). "A single-center randomized, open-label, prospective study to evaluate efficacy and safety of DDK(Drug delivery kit, Welpass) for pain relief after gynecologic laparotomy surgery." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Medical Device : Patients undergoing open surgery for benign gynecological diseases are assigned to the test group and control group in a 1:1 ratio. PCA is applied with the same protocol to both the test and control groups, and DDK (Welpass) is applied only to patients assigned to the test group. For patients assigned to the test group, DDK (Welpass) is applied during the process of suturing the incision site. DDK (Welpass) gel mixed with Ropivacaine 0.75% is applied to the subcutaneous fat layer before suturing the skin at the surgical incision site, and then the skin is sutured. CONDITION: Neoplasms PRIMARY OUTCOME: Dose of fentanyl through PCA SECONDARY OUTCOME: Dose of rescue medication INCLUSION CRITERIA: 1) Those who signed and sealed the clinical trial subject’s written consent to participate in the trial 2) Those who are over 18 years of age but under 80 years of age 3) Patients scheduled for open surgery for benign gynecological diseases using a transverse abdominal incision (Pfannenstiel) 4) Adequate hematological function, liver function, and renal function confirmed in preoperative examination 5) Patients scheduled to use a self‐administered pain control device (PCA)

Kct (2023). "A three-arm randomized phase II study of Dostarlimab alone or with Bevacizumab versus nonplatinum chemotherapy in recurrent gynecological clear cell carcinoma." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Drug : * Subjects are randomly assigned 1:1:1 to one of three groups. 1) Group A: Dostarlimab monotherapy ‐ First 3 cycles: Dostalimab 500mg every 3 weeks, IV ‐ 4 cycles up to 24 months: Dostalimab 1000mg every 6 weeks, IV 2) Group B: Dostarlimab + Bevacizumab combination therapy ‐ First 3 cycles: Dostalimab 500mg every 3 weeks, IV ‐ 4 cycles up to 24 months: Dostalimab 1000mg every 6 weeks, IV ‐ Bevacizumab administered IV at 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity 3) Group C: General chemotherapy (one of doxorubicin, paclitaxel, and gemcitabine) (1) Doxorubicin ‐ administered on day 1 of a 28‐day cycle ‐ 40mg/m2, IV ‐ 1st cycle: 1mg/min, 2nd cycle or more: administration for 60 minutes (2) Paclitaxel ‐ administered on days 1, 8, 15, and 22 of a 28‐day cycle ‐ 80mg/m2 ‐ Intravenous administration for 30 minutes (3) Gemcitabine ‐ administered on days 1, 8, and 15 of a 28‐day cycle ‐ 1000mg/m2 ‐ Intravenous administration for 30 minutes CONDITION: Neoplasms PRIMARY OUTCOME: Progression free survival SECONDARY OUTCOME: Clinical benefit reate Disease control rate Duration of response rate Objective response rate Overall survival Progression free survival 2 Response rate of subsequent therapies Safety and tolerability Time to first subsequent treatment Time to second subsequent treatment INCLUSION CRITERIA: 1. Female patient is at least 18 years of age, 2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements. 3. Patient with histologically proven confirmed recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, and vulva ? Local review by gynecologic pathologist required ? =50% clear cell histology in case of mixed carcinoma ? WT‐1 neg (Only in case of ovarian cancer) Note: In the case of including non‐ovarian clear cell carcinoma with more than 20 cases, the decision is made through discussion with the SPONSOR. 4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 5. Disease progression within 12 months of completing platinum‐based chemotherapy 6. 1‐5 prior lines of therapies 7. Patient with measurable disease according RECIST 1.1 criteria 8. Availability of Tumor tissue for for translational research ‐ A form

Kearley-Shiers, K., et al. (2022). "Intravaginal dehydroepiandrosterone for genitourinary symptoms of the menopause: Is the evidence sufficient?" Post Reproductive Health 28(4): 237-243.
	Intravaginal dehydroepiandrosterone (DHEA) is a locally metabolised estrogen and androgen precursor, licensed in 2018 in the EU for moderate to severe vulvovaginal atrophy in postmenopausal women. A literature search revealed four original trials suitable for appraisal, three evaluating change in dyspareunia or dryness as a primary outcome, one evaluated safety as a primary outcome. In two trials of 255 and 558 women without cancer, the benefit of placebo (nightly vaginal suppositories with a lipophilic base) was a 0.9 and 1 point reduction in dyspareunia as measured on a 3 point scale, an unvalidated outcome measure. With nightly DHEA, dyspareunia was reduced by an additional 0.4 points compared to placebo. When 464 women with gynaecological cancer were randomised, those using nightly plain moisturiser gel reported a reduction of 'most bothersome symptom' (either dyspareunia or dryness) of 1.5 points on a 3 point scale. Those using nightly DHEA reported an additional symptom reduction of 0.3 points. This is also an unvalidated outcome measure. Data evaluating the efficacy of DHEA over placebo is unconvincing and based on unvalidated primary outcome measures that also do not reflect the complex psycho-sexual and socio-cultural components of genitourinary menopausal symptoms. The efficacy and safety data excluded women taking systemic HRT, applies to postmenopausal, not perimenopausal, women and had relatively short follow up. It is important further independent trials use sophisticated and validated assessment tools to better establish the efficacy, safety and cost effectiveness of intravaginal DHEA in clinically representative groups of women before being routinely prescribed.

Kebede, N., et al. (2022). "Treatment patterns and economic burden among cervical and endometrial cancer patients newly initiating systemic therapy." Future oncology (London, England) 18(8): 953-964.
	Aim: To evaluate treatment patterns, healthcare resource use (HCRU) and all-cause healthcare costs among patients with cervical or endometrial cancer newly initiating systemic therapy. Methods: We identified patients with cervical or endometrial cancer newly initiating systemic therapy - a claims-based proxy for advanced disease - between 2014 and 2019, described them by line of therapy (LOT), and summarized the per patient per month (PPPM) HCRU and healthcare costs per LOT. Results: Among 1229 patients with cervical cancer and 2659 patients with endometrial cancer, LOT1 therapies included systemic only (cervical, 50.1%; endometrial, 83.2%) and systemic with radiation therapy (cervical, 49.9%; endometrial, 16.8%). Mean PPPM total costs were: LOT1 (cervical, US$15,892; endometrial, US$11,363), LOT2 (US$20,193; US$14,019) and LOT3+ (US$16,576; US$14,645). Conclusions: Overall, patients received guideline-concordant care and experienced significant economic burden, which increased with LOT.

Kechagias Konstantinos, S., et al. (2022). "Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis." BMJ (Clinical research ed.) 378: e070135.
	Objective: To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment.; Design: Systematic review and meta-analysis DATA SOURCES: PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021.; Review Methods: Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.; Results: 22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I 2 =58%, τ 2 =0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I 2 =0%, τ 2 =0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I 2 =71%, τ 2 =1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low.; Conclusion: HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection.; Systematic Review Registration: PROSPERO CRD42021237350.; Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the NIHR EME for the submitted work; the authors declare no conflict of interest with regards to the presented work; a number of authors are investigators of the NIHR EME funded NOVEL trial (MK, KSK, PS, JD, BS, PN, and IK); this trial is also supported by MSD who supplied the vaccines for the tria . (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Kedia, M., et al. (2023). "Trinuclear rhenium(I)-based metallocages as anticancer agents towards human cervical cancer cells." Dalton transactions (Cambridge, England : 2003) 52(40): 14314-14318.
	The first examples of spherical-shaped trinuclear rhenium(I) organometallic cages displaying cytotoxic, antimetastatic, antiproliferative and DNA-damaging behavior towards a human cervical (HeLa) cancer cell line are reported. The compact design of the metallocages facilitates their interactions with biosystems leading to comparable efficiency to that of the commonly used anticancer drug cisplatin.

Kefeng, S. U. N., et al. (2020). "Advances in clinical research of acupuncture in the treatment of ovulation disorders." 中国医药导报 17(16): 49-53.
	Infertility is a common disease in gynecology. In recent years, the incidence of infertility due to ovulation disorder in women has increased year on year and is on the rise globally. Modern clinical studies show that acupuncture works well in the treatment of ovulation disorders, improving clinical symptoms and increasing clinical pregnancy rates. The effect is clear and the treatment methods are varied, easy to operate without affecting the environment in the womb. In recent years, Chinese and foreign literature, a systematic review of the progress of acupuncture treatment in the treatment of acupuncture. The effects of body needles, plum needles, exertion factors (electric needles, warm acupuncture) on ovulation disorders, and seek better treatment options for clinicians acupuncture to treat ovulation disorders. Theoretical basis and normative clinical guidance for science, improving the scientific nature of acupuncture treatment of ovulation disorders and Effectiveness, and fully promote Chinese medicine to treat more people with infertility for the benefit of the population.

Kellas-Ślęczka, S., et al. (2022). "Pre-operative high-dose-rate brachytherapy in early-stage cervical cancer: long-term single-center results." Journal of Contemporary Brachytherapy 14(1): 43-51.
	Purpose: The aim of the study was to report the outcomes of pre-operative high-dose-rate brachytherapy (pHDR-BT), followed by hysterectomy in patients with early cervical cancer.; Material and Methods: From January, 1998 to December, 2003, 113 women with IB1, IB2, and IIA1 cervical cancer (according to International Federation of Gynecology and Obstetrics [FIGO] 2018) were treated with pHDR-BT, and 6 to 8 weeks later followed by radical hysterectomy. Patients found to have positive lymph nodes, residual cervical cancer, involved parametria, or lymphovascular space invasion (LVSI) received post-operative adjuvant therapy.; Results: Post-operatively, 81.4% of patients had a complete response to pHDR-BT in the cervix, and 18.6% had residual cervical cancer. Failures occurred in 11/113 (9.7%) patients (all were stage IIA1), with pelvic recurrences in 5/113 (4.4%) and distant metastasis (DM) in 6/113 (5.3%). The 5- and 10-year disease-free survival (DFS) rates were 100% for IB1 and IB2, and 86.4% and 81.3% for IIA1, respectively. Lymph node involvement and/or residual cervical cancer correlated with worse DFS. Two vesicovaginal fistulas were observed (one in a patient treated only with pHDR-BT and one in a woman, who underwent adjuvant external-beam radiotherapy [EBRT]). Two rectovaginal fistulas and one case of proctitis were observed in patients treated with adjuvant EBRT.; Conclusions: pHDR-BT in early cervical cancer is well-tolerated and effective in sterilizing tumor cells in the cervix. The growing number of publications in this area may help define an optimal therapeutic scheme, but randomized trials are required to determine the best candidates for this treatment modality.In our opinion, cervical cancer patients with FIGO stage IIA1 are not good candidates for pHDR-BT, and could be given this treatment only after rigorous selection, including assessment with state-of-the-art imaging, due to higher probability of treatment failure.; Competing Interests: The authors report no conflict of interest. (Copyright © 2022 Termedia.)

Keller, E., et al. (2023). "What Features of Fertility Treatment do Patients Value? Price Elasticity and Willingness-to-Pay Values from a Discrete Choice Experiment." Applied Health Economics and Health Policy 21(1): 91-107.
	Background: Infertility is a medical condition affecting an estimated 186 million people worldwide. Medically assisted fertility treatments allow many of these individuals to have a baby. Insights about preferences of patients who have experienced fertility treatment should be used to inform funding policies and treatment configurations that best reflect the patients' voice and the value of fertility treatment to patients. Objective(s): To explore the preferences for fertility treatment attributes of infertile women who had previously undergone or were undergoing fertility treatments-ex post perspective. Method(s): We used data from a stated-preference discrete choice experiment (DCE) among 376 Australian women who had undergone or were undergoing fertility treatment. Respondents chose their preferred treatment choices in 12 hypothetical treatment choice scenarios described by seven attributes (success rates, side effects, counselling/peer support, treatment journey, continuity of care, availability of experimental treatment and out-of-pocket cost). We estimated random parameter logit (RPL) and latent class (LC) models that accounted for preference heterogeneity. The results were used to derive price elasticities of demand and marginal willingness-to-pay (WTP) values for the treatment attributes explored within the DCE survey. Result(s): Income level did not have a significant effect on marginal WTP for fertility treatment attributes. The demand for fertility treatment from an ex post perspective was found to be highly inelastic (treatment cost changes had almost no impact on demand). Success rates and out-of-pocket costs were significant and important predictors of individuals' treatment choices conditional on the attributes and levels included in the study. These were followed by counselling/peer support, side effects, treatment journey, continuity of care, and availability of experimental treatment, in that order. Respondents were willing to pay $383-$524 per one percentage point increase in the treatment success rate and over $2000 and over $3500 to avoid moderate and significant side effects, respectively (values are reported in AU$). Latent class models revealed that the majority of respondents (51%) were risk-averse success-rate seekers. Conclusion(s): Infertile women who had previously undergone or were undergoing fertility treatment valued fertility treatment highly as reflected by highly price-inelastic demand. Success rate of treatment and out-of-pocket costs were the most important attributes and largely determined patients' WTP for fertility treatment relative to the attributes and levels used in the study. While further research should investigate the price sensitivity of women who have not experienced fertility treatment, these results might explain why women continue fertility treatment once they have commenced despite their financial capacity to pay. Future research should also determine patients' price elasticities for a fertility treatment program with multiple treatment cycles.Copyright © 2022, The Author(s).

Kemp, A. and T. El-Toukhy (2020). "A narrative review of adjuvants in fertilisation: evidence for good clinical practice." Journal of Obstetrics & Gynaecology 40(3): 295-302.
	A review of studies published between January 1, 1984 and January 31, 2019 was performed with the aim of analysing the efficacy and adverse effects of commonly used adjuvants to in vitro fertilisation. The authors preferentially selected recent systematic reviews and randomised control trials (where available) from an electronic literature search. The review showed that low molecular weight heparin, corticosteroids and embryo glue may be of use in selected patient groups. Other adjuncts (such as growth hormone, assisted hatching, endometrial disruption and dehydroepiandrosterone) cannot currently be recommended as collated results showed no overall benefit to clinical pregnancy rates or live birth rates. There is a significant lack of robust evidence in this field, and areas in particular need of further research have been highlighted. In conclusion, caution should be exercised in prescribing adjuvants in in vitro fertilisation, either individually or in combination as further research is needed to ascertain their efficacy. Many adjuvants carry the risk of adverse effects which should also be considered. Patients should be clearly informed of the evidence, and where it is lacking, for these treatments. There is a need for further good quality trials to address the questions regarding best practice.

Kemppainen, V., et al. (2022). "Patient-controlled intravenous versus on-demand oral, intramuscular or mcs intravenous administration of oxycodone during medical induced abortion from 64 to 128 days of Gestation: A randomized controlled trial." Contraception 115: 6-11.
	Objective: To compare oxycodone administration via intravenous patient-controlled analgesia (IVPCA) vs on-demand administration during late-first- and second-trimester medically induced abortion. Study design: A prospective randomized controlled study. We enrolled women between 64 to 128 days of gestation in the study between June 2016 and August 2018. Participants were randomized to receive oxycodone either via IVPCA or given on-demand orally, intramuscularly, or intravenously. Pain intensity and satisfaction with care were measured using the visual analogue scale (VAS, 0-100mm). Result(s): Altogether 99 participants were randomized: 48 in IVPCA group and 51 in on-demand group. Median gestational age was similar between groups (74 days [Interquartile range, IQR 69-81] in the IVPCA group vs 72 [69-80] in the control group, p = 0.587). Peak maximal pain was severe in both groups (median pain VAS was 62 [IQR 44-84] and 71 [IQR 56-90], p = 0.52). The odds for severe pain (highest pain VAS>=70) were similar between the groups (IVPCA group OR 0.51 [95% Confidence Interval 0.22-1.18], p = 0.118). In contrast, the odds for mild or tolerable pain (highest pain VAS<=40) were higher in the IVPCA group (OR 4.06 [95% CI 1.05-16.04], p = 0.043). Nevertheless, satisfaction with care was high (VAS 94 [89-100]) in both groups. Of those experiencing severe pain, 94.0% declared pain medication as adequate. Conclusion(s): Women often experience severe pain during medical abortion irrespective of the mode of opiate administration. Oxycodone administration via IVPCA permits women to self-administer analgesics when experiencing pain, raising the odds for mild or tolerable pain during abortion care. Satisfaction with care was high.Copyright © 2022 The Authors

Kenigsberg, S. and Y. Bentov (2021). "Does contemporary ART lead to pre-eclampsia? A cohort study and meta-analysis." Journal of Assisted Reproduction and Genetics 38(3): 651-659.
	Purpose: Recent publications suggested that the risk for pre-eclampsia (PE) is higher with frozen-thawed embryo transfers (FETs) compared to fresh transfers (IVF-ETs). These studies were based on old data that reflects outdated practices. In this paper, we wanted to assess the incidence of PE in current assisted reproductive technology (ART) practice.; Methods: In this cohort study, we present the incidence of PE in all births in the province of Ontario, Canada, for the years 2013-2017 for FET, IVF-ET, and natural conceptions (NC). We also compare our findings to previous studies in a meta-analysis that includes over 4 million births.; Results: The results of our study show that contemporary practice of ART results in comparable risk for PE between FET and IVF-ET; however, the risk is higher than NC.; Conclusion: Current ART practice is associated with a lower risk for PE in frozen embryo transfer; this RR can be further attenuated by using ovulatory endometrial preparation for FETs.

Kershaw, V., et al. (2019). "The effect of percutaneous tibial nerve stimulation (PTNS) on sexual function: a systematic review and meta-analysis." International Urogynecology Journal 30(10): 1619-1627.
	Introduction: Percutaneous tibial nerve stimulation (PTNS) is now an established treatment of pelvic floor dysfunction such as overactive bladder, faecal incontinence or voiding dysfunction. Prevalence of female sexual dysfunction is high in this group. We aim to examine the effect of PTNS on sexual function in this patient group by systematically reviewing the literature and pooling the data in a meta-analysis.; Methods: The literature search was conducted using the MEDLINE, Embase and CINAHL databases. Initial results yielded 74 citations. From these, nine articles met our inclusion criteria. Two articles were doubly reported, leaving seven studies in the systematic review. Only four studies reported sufficient information to be included in our meta-analysis.; Results: Three studies were randomised controlled trials, and five were before-after studies. The number of participants in each study ranged from 11 to 220. Four out of seven studies reported a positive effect of PTNS on sexual function. In the meta-analysis of four studies there was a significant improvement in general sexual function with PTNS (p = 0.04, SMD -0.41, CI[-0.79, -0.03], I 2 = 0%). In a subgroup analysis of the bowel domain of sexual function, there was a significant improvement with PTNS (p = 0.03, MD 17.7, CI [1.92, 33.47], I 2 = 0%).; Conclusion: We report a systematic review on the effect of PTNS on sexual function. Although the studies are of small size, the results are promising in terms of a positive effect of PTNS on sexual function, and we recommend further research in this area.

Kesavan, S., et al. (2023). "The Efficacy of Metformin and Exenatide in Polycystic Ovary Syndrome (PCOS) Patients." Ars Pharmaceutica 64(2): 100-122.
	Introduction: Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that affects 5-10% of women who are their reproductive age. This meta-analysis aims to evaluate the efficacy of metformin and exenatide, respectively, and to compare the efficacy of both drugs using Body Mass Index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and testosterone level. Method(s): Scopus, Science Direct, Oxford Journal, Wiley Online Library, and Medline (through the PubMed search engine) were used in this study. Statistical analysis of the included studies was done using the RevMan 5.4 software. Result(s): There were 6 studies included in the analysis of the study. There was a significant reduction in BMI of PCOS patients with exenatide versus metformin (mean difference = 0.51; 95% confidence interval (CI)= 0.07, 0.96, I 2= 52%; p=0.02). There was also a significant reduction in the testosterone level of PCOS patients with exenatide versus metformin (mean difference = 0.15; 95% confidence interval (CI)= 0.07, 0.22, I 2= 0%; p=0.0002). There was no effect on the mean of LDL-C and of HDL-C when compared between metformin and exenatide This meta-analysis shows that exenatide is effective in reducing BMI and testosterone levels in PCOS patients. Conclusion(s): There were a significant reduction in BMI and testosterone levels of PCOS patients when exenatide was used as compared to metformin. However, there was no effect on the mean of the LDL-C and HDL-C levels of the PCOS patients.Copyright © 2023 Editorial Universida de Granada. All rights reserved.

Keshavarz, S., et al. (2021). "Comparison of midwifery consultation and fluoxetine on ivf outcomes in depressed infertile women: a clinical trial research study." Current Women's Health Reviews 17(2): 176‐184.
	Background: A lot of research has been done to improve the treatment of infertility and increase the quality and effectiveness of performance. Objective: In this randomized clinical trial study (IRCT2014031116911N2), we compared the effect of Fluoxetine and midwifery consultation on infertile women suffering from depression and the focus of the study was on the results of In‐Vitro Fertilization (IVF) treatment. Methods: 90 infertile women who suffered from mild to moderate depression according to the Beck Inventory and had undergone IVF treatment were selected and randomly divided into 3 groups. The control group, the second group, were treated with Fluoxetine 20 mg, and the third group received 6 sessions of midwifery consultation and then the outcomes were reviewed. The amount of cortisol in the women’s sera was measured in three stages and the level of depression and anxiety was measured in two stages. Results: The pregnancy rate in the midwifery consultation group (n=13) was about two times as high as that in the fluoxetine group (n=7) and three times as high as that in the control group (n=4); there was a statistically significant difference among the groups (P=0.016); as to the abortions oc‐curring in each group (P>0.05). Conclusion: Providing the people undergoing IVF treatment with emotional and mental support will increase their chances of pregnancy and this kind of support will be helpful for the patients if it is given in the form of midwifery consultation.

Keshini, S., et al. (2021). "Assessing the efficacy of therapist-assisted eHealth interventions targeting postpartum depression: a systematic review and meta-analysis."
	
Keski, N. P. M., et al. (2023). "Comparison of the Effectiveness of Pelvic Floor Muscle Training, Biofeedback, and Tibial Nerve Stimulation in Overactive Bladder Syndrome: A Prospective Randomized Controlled Study." Journal of Clinical Obstetrics and Gynecology 33(4): 236-244.
	Objective: It was aimed to comparatively assess the effectiveness of pelvic floor muscle training (PFMT), biofeedback (BF), and transcutaneous tibial nerve stimulation (TTNS) treatments in overactive bladder (OAB) patients. Material(s) and Method(s): The patients presented to the urogynecology outpatient clinic between June 2017 and March 2018. They were randomly divided into Group 1: PFMT (n=31), Group 2: PFMT and BF (n=32), and Group 3: PFMT and TTNS (n=33). Patients who received anticholinergic therapy, those who had a previous incontinence surgery or had neurological diseases, those who were pregnant, those who were breastfeeding, those with abnormal liver-kidney functions, persistent urinary infection, or atrophic vaginitis, and those who did not agree to take part in the study were excluded. The OAB Questionnaire (OAB-V8), the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and the Female Sexual Function Index forms were filled out before and after the 12-week treatment. Result(s): Daytime and nighttime urinary frequency, total urinary incontinence, and pad test values were lower after the treatment compared to before in all three groups (p<0.001). A statistically significant decline was seen in post-treatment ICIQSF and OAB-V8 scores compared to pre treatment scores in all three groups (p<0.01). The decrease in daytime urinary frequency was seen to be statistically significant in Group 2, and the values in this group were lower compared to those in Groups 1 and 3 (p: 0.045, p: 0.014, respectively). Conclusion(s): The overall effectiveness of the conservative treatments was determined to be similar. In the selection process, conservative treatment methods should be personalized.Copyright © The Author(s) 2023.

Keskin, T., et al. (2023). "The effects of therapeutic touch and music on sleep quality, menopausal symptoms, and quality of life in menopausal women." Menopause (New York, N.Y.) 30(12): 1221-1229.
	Objectives: This study aimed to examine the effects of therapeutic touch (TT) and music on sleep quality, menopausal symptoms, and quality of life in menopausal women.; Methods: This study was carried out in an experimental model with a pretest, a posttest, and a control group. The study was completed with a total of 108 menopausal women in the TT, music, and control groups. Data were collected using a Participant Information Form, the Pittsburgh Sleep Quality Index, the Menopause Rating Scale, and the Menopause-Specific Quality of Life Scale. TT was applied in the TT group once a week for 4 weeks, and the music group was asked to listen to music for 30 minutes before bedtime every day for 4 weeks. Posttest data were collected in all groups 4 weeks after the pretest. The χ 2 , analysis of covariance, post hoc tests, and partial η2 methods were used to analyze the collected data.; Results: When the effect of the pretest scores was adjusted, compared with the control group, there were statistically significant differences in the posttest scores of the participants in both the TT and music groups in the Pittsburgh Sleep Quality Index dimensions of subjective sleep quality ( P < 0.001), sleep latency ( P ≤ 0.001), and sleep disturbances ( P < 0.05). When the effect of the pretest scores was adjusted, compared with the control group, there were statistically significant differences in the posttest scores of the participants in both the TT and music groups in the Menopause Rating Scale and Menopause-Specific Quality of Life Scale ( P < 0.001).; Conclusions: It was concluded that TT and music increased sleep quality (subjective sleep quality, sleep latency, and sleep disturbances) and quality of life and reduced menopausal symptoms.; Competing Interests: Financial disclosure/conflicts of interest: None reported. (Copyright © 2023 by The Menopause Society.)

Keukens, A., et al. (2024). "The effect of surgery or medication on pain and quality of life in women with endometrioma. A systematic review and meta-analysis." European Journal of Obstetrics and Gynecology and Reproductive Biology 293: 95-105.
	For patients with endometrioma it is unclear what treatment: surgery and/or medication, is more effective in reducing pain and improving quality of life (QoL). This systematic review and meta- analysis aimed to provide an overview of the existing evidence on the effects of surgery and/or medication (i.e. analgesics and/or hormonal medication) on pain and QoL. A search through CENTRAL, MEDLINE and Embase was conducted. The study population had to be women treated for endometrioma. Retrospective or prospective studies reporting about QoL and/or the following types of pain were reviewed: dysmenorrhea, dyspareunia, chronic pelvic pain, and pain that was not well defined in the included article (referred to as pain). We performed a meta-analysis on mean visual analogue scale (VAS) scores and proportions of patients experiencing different types of pain over time. QoL was described narratively. Out of 11.515 articles, 76 studies including 7148 patients were included for the systematic review. The meta-analysis consisted of 52 studies including 4556 patients. No studies compared medication with surgery. And there were no studies on analgesics. Meta-analysis showed that surgery and/or medication often reduced VAS scores and proportions of all types of pain over time. Surgery and medication combined seems more effective in reducing VAS scores of pain compared to surgery alone, but not to medication alone (estimated mean difference = 0.17, p < 0.0001 and -0.98, p = 0.0339). QoL improved after medication (follow up <= 12 months) and QoL was unchanged or worsened after surgery and medication combined (follow up <= 24 months). However, these were results from a total of 5 studies. Both surgery and medication reduce endometriosis-related pain in patients with endometrioma. However, there is lack of uniform, good quality data comparing surgery with medication to draw firm conclusions. For better-informed treatment decisions, further studies including a standardized core-outcome set at fixed follow-up times, are necessary.Copyright © 2023 The Authors

Keyser, L., et al. (2021). "Rehabilitative care practices in the management of childbirth-related pelvic fistula: A systematic review." International Urogynecology Journal 32(9): 2311-2324.
	Introduction and hypothesis: Childbirth-related pelvic fistula (CRF) often requires surgery, yet even with successful repair, mental health conditions, musculoskeletal impairments, urinary and fecal incontinence and sexual dysfunction persist for many women. Postoperative rehabilitation, (i.e., physiotherapy, mental health counseling) may address these concerns and has been reported for this population. This review aims to summarize the literature and level of evidence of rehabilitative care practices in fistula care to inform clinical practice, research and policy recommendations. Method(s): A systematic literature review was conducted using Africa-Wide Information, CINAHL, Cochrane, Embase, Global Health, PAIS Index, PubMed and SCOPUS searching keywords and MeSH terms to identify women with CRF admitted for surgery. Two researchers progressively screened titles, abstracts and full-text articles. Eligible articles were classified primary if intervention details and outcomes were reported or secondary if rehabilitation was described, but no specific outcomes reported. Relevant study details, strengths and limitations, and key findings were extracted. Result(s): Eighteen articles were included: eight primary, ten secondary. Primary articles reported on urethral plugs for postoperative urinary incontinence (UI) (2/8), menstrual cup to manage UI (1/8), physiotherapy and health education (3/8) and mental health counseling (2/8). Secondary articles describe rehabilitation components in the context of program descriptions, qualitative analyses or reviews. All evidence was low or very low quality. Conclusion(s): Research on rehabilitative care is very limited and highlights inconsistencies in practice. This review provides support for the feasibility of rehabilitation and establishes the need for future interventional studies that involve a comparator and reliable outcome measures.Copyright © 2021, The International Urogynecological Association.

Keyvani, V., et al. (2023). "Insight into RNA-based Therapies for Ovarian Cancer." Current Pharmaceutical Design 29(34): 2692-2701.
	Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Kft, F. (2023). Zinc-containing Vaginal Gel and Oral Fluconazole for Vulvovaginal Candidiasis.
	No Results Available Drug: JUVIA zinc containing vaginal gel treatment|Drug: Fluconazole 150Mg Tab Clinical cure|Time to initial symptom resolution.|Vaginal fungal culture for Candida species.|Clinical cure at days 28, 56, 84|Candida severity score|PRA-1 level|CVL zinc level|Vaginal pH|Vaginal neutrophil count|Concentration of calprotectin, IL-1beta, IL-8 in the vaginal sample by ELISA|Vaginal measurement of CEF1, ACT1, PRA1, ECE1, HWP1, SAP6 expression by qRT-PCR|Vulvovaginal symptoms questionnaire|Vaginal Health Index|Reported Adverse Events (AEs) and Serious Adverse Events (SAEs) Female Not Applicable 76 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2023VVC January 7, 2025

Khabarov, S. V., et al. (2021). "[The effectiveness of the transcranial electrical stimulation method in obstetrics and gynecology]." Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury 98(4): 62-69.
	The review examines the use of protective (endorphinergic and serotonergic) mechanisms of the brain in obstetrics and gynecology. To review the current state of the problem an analysis of the eLIBRARU, PubMed, Embase, MEDLINE, Cochrane databases was carried out, and works for 2015-2020 were selected. It has been shown that the method of non - invasive non - drug effects on the human body - transcranial electrical stimulation (TES) - activates and accelerates reparative processes, normalizes psychophysiological status, has anti-inflammatory and immune-stimulating effects, has an onco-protective effect, stabilizes the autonomic nervous system, provides drug - free disturbance homeostasis in general. This makes it possible to successfully use TES in obstetrics and gynecology in such pathological conditions as the threat of pregnancy termination at different times, nausea and vomiting of pregnant women, preeclampsia, pathological prelaminar period, menstrual dysfunction, climacteric syndrome, leiomyoma and endometriosis of the uterus, endometrial hyperplastic processes, chronic inflammatory diseases of the pelvic organs with pain syndrome, surgery and obstetrics care. TES is characterized by high efficiency, safety, ease of use, availability and economic profitability. TES reduces the number of prescribed drugs and shortens the recovery time. This method is used both as monotherapy and as a component of a complex action including medication and non-medication. The results of the TES studies presented in the review complement each other and demonstrate the importance of modern alternative methods of treatment, and the authors of these studies are unanimous in their opinion on the fruitfulness of the use of transcranial electrical stimulation as a type of non-drug therapy in various fields of obstetrics and gynecology.

Khadrawi, A. M., et al. (2023). "Recurrent Implantation Failure." Journal of Pharmaceutical Negative Results 14(2): 1487-1488.
	Implantation failure can occur during any of the three stages of implantation. It can be classified into four main categories, altered endometrial receptivity, embryonic defects, abnormal embryo-endometrial cross-talk and impairment in the regulation of immunologic mediators. Recurrent implantation failure needs a wide range of investigations. Several methods have been performed for RIF management but there is little consensus on the most effective one . Recently, some progress in treating RIF and thin endometrium has been made with the use of the PRP. Its main idea in patients with previous ET failures is based on the regulation of expression of growth factors and cytokines in the endometrium.Copyright © 2023 Authors. All rights reserved.

Khair, A. F., et al. (2021). "COST COMPARISON OF HIGHLY PURIFIED HUMAN MENOPAUSAL GONADOTROPIN (HP-HMG) VERSUS RECOMBINANT FOLLICLE-STIMULATING HORMONE (RFSH) FOR CONTROLLED OVARIAN STIMULATION IN US HIGH-RESPONDER PATIENTS BASED ON THE MEGASET-HR TRIAL." Fertility and Sterility 116(3): e267.
	Objective: Assess the cost difference between treatment groups [highly purified human menopausal gonadotropin (HP‐hMG) and recombinant follicle stimulating hormone (rFSH)] after three cycles (one fresh and two frozen transfers). Materials and Methods: A health economic model was developed to assess the use of either HP‐hMG or rFSH capturing healthcare costs for a cohort of high‐responder women undergoing up to three cycles of treatment (one fresh and two frozen cycles should a live birth not be achieved in previous cycles). This discrete event simulation model is based on data from the MENOPUR IN GnRH (Gonadotropin releasing hormone) ANTAGONIST SINGLE EMBRYO TRANSFER ‐ HIGH RESPONDER (MEGASET‐HR) trial (NCT02554279), where 620 ovulatory women aged 21‐35y with BMI 18‐30 kg/m2 and serum anti‐Müllerian hormone (AMH) ≥5 ng/mL were randomized 1:1 to a 150 IU dose of HP‐hMG (N=311) or rFSH (N=309) in a GnRH antagonist cycle with dose adjustments based upon response allowed from day 6 onward. Fresh transfer of a single blastocyst was performed in hCG‐triggered cycles with GnRH agonist trigger used and all embryos frozen if the risk of OHSS was high. Live births resulting from fresh and all frozen transfers occurring within 6 months of randomization were collected. The study achieved its primary endpoint of non‐inferiority for ongoing pregnancy after fresh cycle with results previously reported1. Transition probabilities in the model were derived from the trial data and data on costs of procedures and cost of HP‐hMG and rFSH were identified from the literature2. Results: A cohort matching the trial population was simulated in the model. Baseline patient age was 30.25 ±3.04 years, mean infertility duration 37.01±1.54 months, mean baseline prolactin was 13.67±0.38 ug/L, mean baseline FSH was 6.11±0.1 U/L, and mean baseline AMH was 7.67±0.17 ng/mL. Based on the efficacy and safety outcomes of the MEGASET‐HR trial, modelled rates per 1000 women in the HP‐hMG arm were 917 embryos transferred, 522 ongoing pregnancies, 500 live births and 79 OHSS events. In the rFSH arm, corresponding rates were 1037 embryos transferred, 501 ongoing pregnancies, 484 live births and 234 OHSS events. Results of the simulation demonstrated a cost reduction of $2,017 per ongoing pregnancy and $1,908 per live birth for the HP‐hMG treatment arm compared to the rFSH treatment arm in a predicted high‐responder. The average costs per ongoing pregnancy and live birth were $26,762 and $39,554 for HP‐hMG and $28,779 and $41,462 for rFSH. Conclusions: Compared to rFSH, HP‐hMG is estimated to reduce cost per pregnancy and cost per live birth in a predicted high responder population with baseline characteristics similar to patients in the MEGASET‐HR trial in the US. Further research is warranted to determine whether these results also apply to low and normal responder populations. Impact Statement: Cost to achieve a live birth, along with efficacy and safety, should be considerations when determining treatment options. Cost can be a significant barrier to treatment for many patients seeking infertility care. Ferring Pharmaceuticals AS, Copenhagen, Denmark References: 1. Witz CA, et al. Fert Steril August 2020, Volume 114, Issue 2, Pages 321‐330, 2. Robins JC, et al. F&S Reports December 2020, Volume 1, Issue 3, Pages 257‐263

Khalaf Reema, A. and M. Awad (2023). "Lycopene as a Potential Bioactive Compound: Chemistry, Extraction, and Anticancer Prospective." Current cancer drug targets 23(8): 634-642.
	Lycopene, a potential bioactive agent, is a non-pro-vitamin A carotenoid recognized as a potent antioxidant. It is extracted from plants like tomatoes, watermelons, red carrots and papayas and has remarkable health benefits. A significant amount of research has been assisted to date to establish the anticancer activity of lycopene. Our review enhances information about the promising anticancer potential of this compound. The biological activity of lycopene has been described in several studies in regard to pancreatic, breast, prostate, liver, gastric, ovarian, kidney, skin, intestine, brain and spinal cord cancers. Lycopene resists cancer by inhibition of apoptosis, induction of cell proliferation, cell invasion, cell cycle development, metastasis and angiogenesis. The mechanisms of anticancer action of lycopene are attributed to the management of certain signal transduction pathways, such as modulation of insulin-like growth factors system, PI3K/Akt pathway, modification of important gene expression, inhibit the activity of sex steroid hormones, and the conversation of mitochondrial behavior. Hence, this review focuses on current knowledge of sources, extraction techniques, and chemistry of lycopene, as well as the prospective mechanisms of action related with its anticancer activity. Also, it summarizes the background information about lycopene and the most current research with consideration to its aspect in treating several types of cancer together with future directions. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Khalaf Zeinab, M., et al. (2023). "Valid and Invalid Indications for Osteopathic Interventions: A Systematic Review of Evidence-Based Practices and French Healthcare Society Recommendations." Cureus 15(11): e49674.
	The main aim of this study was to determine the level of evidence in the literature for the main indications of osteopathy as recommended by the French osteopathy societies. This systematic review followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and evaluated articles published between January 2012 and January 2022 with one modification: when level one evidence studies were available, level two to five studies were excluded. Sources included PubMed, the Cochrane library, the French National Health Authority (HAS) and its affiliates. Inclusion criteria were level one published studies on the indications for osteopathic treatment in French and English, and level two to three studies when no level one studies were available. The level of evidence assessment was based on the Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence classification. The primary outcome was the level of evidence in the literature supporting osteopathic practices. The secondary outcome was to assess French professional osteopathy recommendations and French HAS guidelines in relation to the scientific literature. A total of 51 articles and nine recommendations from the HAS and its affiliates met the inclusion criteria for the systematic review. Analysis of the studies revealed 41 osteopathic indications from French osteopathy societies for musculoskeletal, neurosensory, psychological, pediatric, gynecological, digestive, and pulmonary disorders. High-level scientific evidence supported the use of osteopathy for low back pain, sciatica, cervical radiculopathy, and ankle sprain. There was moderate evidence for tension headache, temporomandibular joint disorder, endometriosis, and low back and pelvic pain in pregnant women. HAS recommended five indications, while nine indications were supported in the scientific literature. Osteopathy has been shown to have evidence-based benefits for a range of conditions, in particular for musculoskeletal and neurosensory disorders.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Khalaf et al.)

Khalafi, M. and E. Symonds Michael (2020). "The impact of high-intensity interval training on inflammatory markers in metabolic disorders: A meta-analysis." Scandinavian journal of medicine & science in sports 30(11): 2020-2036.
	Introduction: High-intensity interval training (HIIT) is considered a time-efficient strategy to improve metabolic health. We performed a systematic meta-analysis to assess the effects of HIIT on inflammatory markers and adipo-cytokines compared with control conditions (CON) or moderate-intensity continuous training (MICT) in individuals with metabolic disorders.; Methods: Up to January 2020, electronic databases were searched for HIIT interventions based on populations with metabolic disorders including diabetes, metabolic syndrome, polycystic ovary syndrome, non-alcoholic fatty liver disease or overweight/obesity, with outcome measurements that included IL-6, TNF-α, CRP, leptin or adiponectin and training ≥2 weeks. Random-effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (Cis), and potential moderators were explored.; Results: Twenty-nine studies involving 841 participants were included in the meta-analysis. HIIT improved circulating adiponectin (P = .02), leptin (P = .02), and TNF-α (P = .003) when compared to CON. There were no differences between groups in IL-6 and CRP. Intervention duration was a significant moderator for the effect of HIIT on IL-6, and leptin (P < .05).; Conclusion: High-intensity interval training improves circulating TNF-α, leptin and adiponectin, thereby indicating that it may be an effective and time-efficient intervention for controlling low-grade inflammation in individuals with metabolic disorders. (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Khalesi, Z. B., et al. (2019). "Efficacy of chamomile in the treatment of premenstrual syndrome: A systematic review." Journal of Pharmacopuncture 22(4): 204-209.
	Premenstrual syndrome (PMS) encompasses a vast array of physical and psychological symptoms. Of the herbal supplements mentioned for remedy PMS symptoms, chamomile used as an effective herbal medicine. The overall purpose of this review was to determine the efficacy of chamomile on the treatment PMS. An extensive research review using Web of Science, the Cochrane Controlled Trials Register database, PubMed, Chinese Biomedical Database (CBM), CINAHL, China National Knowledge Infrastructure (CNKI), Psych INFO, Social Science Research Network, SID, Google Scholar, Iran Doc, Magiran and Iran Medex. Eligible studies were identified from English and Persian databases, published between 1990 and 2019. Studies were screened independently by two researchers who performed the data extraction. Of Twenty-seven studies identified, Eight RCTs met our inclusion criteria. Chamomile has been used to treat PMS relief because of therapeutic properties such as anti-inflammatory effects (Chamazulene and alpha-Bisabolol); anti-spasmodic effects (Apigenin, Quercetin, and Luteolin, Metoxicomarin, Matrisin, and Phytoestrogens); anti-anxiety effects (Glycine, Flavonoid). The results of this review show that Chamomile is effective for the treatment of PMS. Based on these results, we believe that Chamomile can be used as good herbal medicine to treat in women with PMS.Copyright © 2019 Korean Pharmacopuncture Institute.

Khalid, B., et al. (2021). "Surgical management for endometriosis affecting the rectum and colon: A systematic review."
	
Khalife, T., et al. (2022). "Retroperitoneal Causes of Genitourinary Pain Syndromes: Systematic Approach to Evaluation and Management." Sexual Medicine Reviews 10(4): 529-542.
	INTRODUCTION: Women with pelvic pain commonly report pain in their ovaries, vagina, uterus, or bladder. These symptoms may be caused by visceral genitourinary pain syndromes but also may be caused by musculoskeletal disorders of the abdomen and pelvis. Understanding neuroanatomical and musculoskeletal factors that may contribute to genitourinary pain is important for evaluation and management. OBJECTIVE(S): This review aims to (i) highlight the importance of clinical knowledge of pelvic neuroanatomy and sensory dermatomal distribution of the lower abdomen, pelvis, and lower extremities, exemplified in a clinical case; (ii) review common neuropathic and musculoskeletal causes of acute and chronic pelvic pain that may be challenging to diagnose and manage; and (iii) discuss female genitourinary pain syndromes with a focus on retroperitoneal causes and treatment options. METHOD(S): A comprehensive review of the literature was performed by searching the PubMed, Ovid Embase, MEDLINE, and Scopus databases using the keywords "chronic pelvic pain," "neuropathy," "neuropathic pain," "retroperitoneal schwannoma," "pudendal neuralgia," and "entrapment syndromes." RESULTS: Retroperitoneal causes of genitourinary pain syndromes have substantial overlap with common conditions treated in a primary care setting. Thus, a comprehensive and systematic history and physical examination, with focused attention to the pelvic neuroanatomy, is key to establishing the correct diagnosis. In the clinical case, such a comprehensive approach led to the unexpected finding of a large retroperitoneal schwannoma. This case highlights the intricacy of pelvic pain syndromes and the complex nature of their possible overlapping causes, which ultimately affects treatment planning. CONCLUSION(S): Knowledge of the neuroanatomy and neurodermatomes of the abdomen and pelvis, in addition to understanding pain pathophysiology, is critical when evaluating patients with pelvic pain. Failure to apply proper evaluation and implement proper multidisciplinary management strategies contributes to unnecessary patient distress, decreased quality of life, and increased use of health care services.Copyright © 2022, International Society for Sexual Medicine. Published by Elsevier.

Khalil, A. M., et al. (2021). "Reliable and rapid smooth extubation after 'ketamine-propfol mixture' for induction of general anesthesia in laparoscopic drilling of polycystic ovary: a randomized, double-blind, comparative study." Anesthesiology and pain medicine 11(2): e113919.
	Background: Ketofol's effect on hemodynamics and the airway response during inducing general anesthesia has been studied previously. However, ketofol's effect on the smoothness of extubation has not been studied yet. Objective(s): We aimed to assess ketofol's effect on the smoothness of extubation and compare it with propofol for inducing general anesthesia. Method(s): This double‐blind, randomized, and controlled study was conducted on 106 class I and II female patients with the 'Amer‐ican Society of Anesthesiologists Physical Status (ASAPS),' aged 18‐40 years, scheduled for laparoscopic drilling for polycystic ovary disease under general anesthesia. The patients were assigned to two groups of 53 patients each: Group KP = ketofol and Group P = propofol. Result(s): There was an excellent sedation score during suction and extubation in the ketofol group. The airway response and smoothness of extubation were better in the ketofol group than in the propofol group. Conclusion(s): Ketofol as an induction anesthetic agent more effectively attenuated the airway response during extubation than only propofol.

Khalili-Tanha, G., et al. (2022). "The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-surgical Adhesions." Current Pharmaceutical Design 28(3): 180-186.
	Background: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, few improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered a blood pressure regulator. However, recent studies have indicated that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and wound healing. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion.; Methods: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion.; Results: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are used for targeting the RAS system, and some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including telmisartan, valsartan, and enalapril.; Conclusion: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting the Renin-Angiotensin System may help to prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Khan, S., et al. (2023). "Invasiveness of endometrial cancer cell lines is potentiated by estradiol and blocked by a traditional medicine Guizhi Fuling at clinically relevant doses." Frontiers in Oncology 12: 1015708.
	The Traditional Chinese medicine, Guizhi Fuling (here called Fuling), has been confirmed in meta-analysis studies to reduce recurrence of endometriosis and improve pregnancy outcomes; however, the possible use of Fuling as a fertility-preserving treatment in endometrial cancer has not previously been tested. Results here are the first to demonstrate dose-dependent inhibition of cell motility by Fuling in two endometrial cancer cell lines, classified as Grade I which is responsive to progesterone treatment, and Grade III (MFE-280) which is resistant. The major outcome of this study was the novel demonstration that Fuling (30-80 µg/ml) significantly inhibits invasiveness in both high and low grades of EC cells, achieving 70-80% block of trans-barrier migration without cytotoxicity. This effective dose range is estimated to be comparable to that used in human clinical trials and traditional practice. Results here further show that clinically relevant doses of Fuling override the motility-promoting effects of estradiol in endometrial cancer cell lines. Medroxyprogesterone acetate has to date been the standard therapy to treat metastatic or inoperable endometrial cancers; however, success rates are low with high rates of recurrence, due in part to acquired resistance to medroxyprogesterone acetate therapy. The discovery here that Fuling appears to control the spread of treatment-resistant advanced cancers is an exciting prospect.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Khan, Varricchio, Ricciardelli and Yool.)

Khare, S. (2023). "Efficacy of Dr. SKS Hair Booster Serum in the Treatment of Female Pattern Alopecia in Patients With PCOS: An Open-Label, Non-randomized, Prospective Study." Cureus 15(9): e44941.
	Background Many patients with polycystic ovary syndrome (PCOS) exhibit female pattern hair loss (FPHL). A more advanced, efficient, and suitable therapeutic approach is required to effectively manage FPHL in patients with PCOS. Aim Dr. SKS Hair Booster Serum is composed of copper, niacinamide, hyaluronic acid, thiamine, riboflavin, and biotin; each of these constituents has demonstrated individual efficacy in promoting hair growth and enhancing hair quality. We hereby assess the effectiveness of this novel hair formulation in treating FPHL in PCOS. Methods This was an open-label, non-randomized, multicenter, prospective, large study with a wide range of age groups. The study involving 1,000 females aged 25-50 years, diagnosed with PCOS and having complaints of FPHL with Ludwig grades I and II. Each patient received a monthly session of Dr. SKS Hair Booster Serum, with 1 mL of serum administered through injection into the superficial layer (dermis) of the scalp using a tiny infusion via an insulin syringe, mesotherapy, or via a derma roller/derma pen. All the patients were subjected to standard global photography, video microscopic assessment (vellus hair counts, terminal hair counts, and hair shaft diameter), and a subject self-assessment questionnaire at baseline and six months after the treatment. Results After six months of the treatment, the hair shaft diameter, terminal hair counts, and hair growth rate were significantly increased than baseline (p≤0.0001), and a significant reduction was noted in vellus hair counts than baseline measurement (p<0.00001). These findings are suggestive of improved hair regrowth after the treatment. No adverse events were recorded during the study. Statistically significant improvements were observed in hair parameters (overall hair fall rate, hair texture, hair volume, and scalp itching) after six months of treatment than baseline. Conclusion Dr. SKS Hair Booster Serum has been shown to be an effective treatment for FPHL in patients with PCOS. This study marks the first investigation into the use of Dr. SKS Hair Booster Serum in patients with PCOS.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Khare et al.)

Khattak, H., et al. (2022). "Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis." Human Reproduction Update 28(3): 400-416.
	Background: Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below -190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series.; Objective and Rationale: The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen-thawed transplant, fresh or donor graft.; Search Methods: The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model.; Outcomes: The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32-43%) for pregnancy, 28% (95% CI: 24-34%) for live birth and 37% (95% CI: 30-46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9-155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4-729; mean difference: 228.24; 95% CI: 180.5-276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8-84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9-17.3; mean difference 61.8; 95% CI: 57-66.6). The median time to return of FSH to a value <25 IU/l was 19 weeks (interquartile range: 15-26 weeks; range: 0.4-208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4-3.4 years; range: 0.7-5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functions in women. Further studies with larger samples of well-characterized populations are required to define the optimal retrieval, cryopreservation and transplantation processes.; Wider Implications: Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function. Although this technology was developed as a fertility preservation option, it may have the scope to be considered for endocrine function preservation. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Khaw Shen, C., et al. (2020). "Systematic review of pregnancy outcomes after fertility-preserving treatment of uterine fibroids." Reproductive Biomedicine Online 40(3): 429-444.
	The aim of this study was to compare pregnancy outcomes after medical (ulipristal acetate [UPA]), surgical (myomectomy) and radiological (uterine artery embolization [UAE] or thermal ablation) therapy for fibroids in women. A systematic review was conducted and ScienceDirect, PubMed, Web of Science and Cochrane Library databases were thoroughly searched from 2000 to 2018. Only primary research was included with independent extraction of articles by two reviewers, using a standardized form. Data were available on 12 pregnancies after treatment with UPA, 1575 after myomectomy, 424 after UAE and 420 after fibroid ablation. Results after UPA therapy were not included in the statistical analysis owing to the limited number of cases; most were ongoing pregnancies. High rates of successful pregnancy were seen after myomectomy (75.6%) and fibroid ablation (70.5%), whereas pregnancies after UAE had the lowest live birth rates (60.6%) and highest miscarriage rates (27.4%) (both P < 0.001 versus other treatments). In conclusion, myomectomy is associated with better pregnancy outcomes than other fertility-preserving treatments for fibroids. At present, UPA is the only medical treatment for fibroids; however, the evidence on pregnancy outcome is limited. In the absence of randomized controlled trials, these data may be of benefit in advising patients about future pregnancy. (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Khayrutdinov, E., et al. (2021). "A randomized comparison of transradial and transfemoral access in uterine artery embolization." Diagnostic and interventional radiology (Ankara, Turkey) 27: 59‐64.
	PURPOSE: We aimed to compare duration of uterine artery embolization, radiation exposure, safety and quality of life associated with the procedure in patients undergoing uterine artery embolization using transradial and transfemoral access. METHOD(S): This randomized controlled trial was conducted from February 2013 to March 2017 in three hospitals. Transradial access was used in 78 patients and transfemoral access in 75 patients. Clinical characteristics of the patients were comparable between the two groups. Patients were evaluated for the success and duration of the procedure, radiation exposure, major and minor complications. Quality of life associated with the procedure was assessed among patients with uterine fibroids. RESULT(S): Embolization procedures were successfully performed in all patients in both groups. The duration of uterine artery embolization (32.27+/‐7.99 vs. 39.24+/‐9.72 minutes, P < 0.001), uterine artery catheterization time (12.36+/‐5.73 vs. 19.08+/‐6.06 minutes, P < 0.001) and radiation exposure (0.28+/‐0.14 vs. 0.5+/‐0.21 mZv, P < 0.001) were significantly lower in the transradial access group. The rate of major (0% vs. 2.7%, P = 0.37) and minor (11.53% vs. 17.3%, P = 0.42) complications was comparable between the two groups. Transradial access was associated with a statistically significant improvement in the quality of life associated with the procedure among patients with uterine fibroids. CONCLUSION(S): Transradial access in uterine artery embolization has the same efficacy and safety compared to transfemoral access. This access reduces radiation exposure and duration of the procedure.

Kheil Mira, H., et al. (2022). "Platelet-rich plasma: inconclusive evidence of reproductive outcomes in menopausal women." Journal of Assisted Reproduction and Genetics 39(9): 1987-1991.
	Purpose: The use of platelet-rich plasma is being investigated in reproductive medicine and clinically promoted as a fertility treatment for menopause. We aimed to review the literature on the impact of PRP on fertility in menopause.; Methods: A literature search was performed using the PubMed and MEDLINE search engines. The search was limited to the English language. Articles studying PRP use in menopause were selected for the purpose of this review.; Results: Limited case reports and case series studied fertility outcomes of PRP in menopause. Randomized controlled trials are lacking. Furthermore, no studies have been conducted to evaluate the effect of different PRP concentrations, injection techniques, or side effects on reproductive outcomes in menopausal women.; Conclusion: There is a dearth of data to support the routine implementation of intraovarian PRP injections for fertility restoration in menopausal women. Patients considering such therapy need to be well aware of the lack of adequate data for PRP use in menopause and should be counseled accordingly. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Kheil Mira, H., et al. (2022). "Endometrioma and assisted reproductive technology: a review." Journal of Assisted Reproduction and Genetics 39(2): 283-290.
	Purpose: Endometriomas are a common cause of infertility necessitating assisted reproductive technology (ART). It had been previously thought that surgical removal of the endometriomas prior to ART would improve reproductive outcomes, but recent data suggests that surgical cystectomy might affect the ovarian reserve, decreasing the chances of ART success. The aim of this article is to review the literature on the effects of endometrioma surgery on ART outcomes providing an overview of the current evidence and assessing the need for further studies.; Methods: A literature search was performed using PubMed and MEDLINE databases to identify studies that discuss endometriomas and assisted reproductive technology before versus after surgery.; Results: In women with an endometrioma requiring ART, growing evidence suggests that surgery might result in damage to the ovarian reserve and further decrease chances of fertility. However, pregnancy rates, implantation rates, fertilization rates, and live birth rates seemed to be consistently similar across both groups.; Conclusion: The current evidence is inconclusive on whether endometriomas should be surgically removed prior to ART. Further large randomized controlled trials are needed for a definite answer, and until then, management should be individualized. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Khitaryan, A. G., et al. (2021). "Are there any advantages of 3D laparoscopic technologies in surgery for rectocele and rectal prolapse?" Koloproctologia 20(4): 56‐69.
	AIM: To assess results of 3D laparoscopic ventral mesh rectopexy versus traditional 2D laparoscopy for rectocele and rectal prolapse. PATIENTS AND METHODS: A prospective randomized study (NCT 04817150) included patients aged 18 to 70 years who underwent laparoscopic ventral mesh rectopexy for rectocele and/or rectal prolapse. The assessment included operation time, intraoperative blood loss, complications rate and their severity by Clavien‐Dindo scale, the pain intensity by VAS, the volume of the fluid collection in the implant site 2–3 days and 2–3 weeks after the procedure. The surgeon’s comfort and ergonomics when using 3D systems was evaluated using POMS questionnaire. The late results were assessed by recurrence rate, functional results — by Cleveland Clinic Constipation scale score, Incontinence scale score, P‐Qol, and PGII. RESULTS: The study included 29 patients of the main and 32 patients of the control group. The follow‐up was 21 ± 20.3 months. One complication developed in the control group (p = 1.0). The operation time in the main group was 74.1 ± 14 minutes (87.1 �� 24.3 minutes in controls, p = 0.01). The intraoperative blood loss was 19.8 ± 9.6 ml in the main group (55 ± 39.2 ml in controls, p = 0.001). The pain intensity was significantly lower in the main group (18.0 vs 22.5 points, p = 0.03). The volume of fluid collection 2–3 after surgery mesh site was 21.2 ± 9.7 cm3 in the main group (30.7 ± 25.6 cm3 in the control group, p = 0.02). The POMS scale assessment for a surgeon in the main group was 56.4 ± 33.5 points (87.3 ± 30.8 points in the control group). A follow‐up examination 12 months postop revealed no recurrence in both groups (p = 1.0). The main and the control group showed no significant differences in functional outcomes. CONCLUSIONS: The use of 3D laparoscopic ventral mesh rectopexy for rectocele and rectal prolapse is comparable in late results with traditional laparoscopic procedure. However, it takes less operation time, lower pain intensity, less intraoperative blood loss, smaller fluid collection at mesh site, better comfort and ergonomics for surgeon.

Khizer, Z., et al. (2021). "Drug Delivery Approaches for Managing Overactive Bladder (OAB): A Systematic Review." Pharmaceuticals (Basel, Switzerland) 14(5).
	Overactive bladder syndrome (OAB) is characterised by urgency symptoms, with or without urgency incontinence, usually with frequency and nocturia and severely affects the quality of life. This systematic review evaluates the various drug delivery strategies used in practice to manage OAB. Advanced drug delivery strategies alongside traditional strategies were comprehensively analysed and comparatively evaluated. The present review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. A total of 24 studies reporting the development of novel formulations for the treatment of OAB were considered eligible and were further categorised according to the route of drug administration. The review found that various drug delivery routes (transdermal, intravesicular, oral, vaginal and intramuscular) are used for the administration of drugs for managing OAB, however, the outcomes illustrated the marked potential of transdermal drug delivery route. The findings of the current review are expected to be helpful for pharmaceutical scientists to better comprehend the existing literature and challenges and is anticipated to provide a basis for designing and fabricating novel drug delivery systems to manage OAB.

Khorasani, F., et al. (2020). "Physiotherapy and pelvic floor muscle exercises for the prevention and treatment of pregnancy-related pelvic floor dysfunctions: A systematic review and meta-analysis." Int. J. Women's Health Reproduction Sci. 8(2): 125-132.
	
Khunda, A., et al. (2019). "Sacral neuromodulation and sexual function: a systematic review and meta-analysis of the literature." International Urogynecology Journal 30(3): 339-352.
	Introduction and Hypothesis: Sexual function is being increasingly recognized as an important patient-reported outcome. Sacral neuromodulation (SNM) is a treatment with an expanding list of indications. The effect of sacral neuromodulation on sexual function has been examined in a number of studies with variable results. In this review, we aim to systematically review the literature and pool the data if appropriate.; Methods: The literature search was conducted primarily on the Healthcare Databases Advanced Search (HDAS) platform using the Medline, EMBASE and CINHAL search engines. Of 196 initial citations, 17 articles met our predefined inclusion criteria. Thirteen studies reported enough information to be included in our meta-analysis. RevMan5 software was used for analysis.; Results: Eight of 17 studies reported a positive effect of SNM on sexual function. Pooled analysis of data from 11 studies involving 573 patients before SNM and 438 patients after SNM showed significant improvement in sexual function (SMD = -0.39; 95% CI: -0.58 to -0.19; p = 0.0001). The results remained significant in most subgroup analyses except in patients suffering from fecal incontinence.; Conclusions: SNM in women with pelvic floor disorders, especially bladder dysfunction, seems to have a positive effect on sexual function. This needs to be verified in adequately powered primary research using sexual function as the primary outcome.

Kiel Ida, A., et al. (2020). "Improving reproductive function in women with polycystic ovary syndrome with high-intensity interval training (IMPROV-IT): study protocol for a two-centre, three-armed randomised controlled trial." BMJ Open 10(2): e034733.
	Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age and the leading cause of anovulatory infertility. Women with PCOS have a 15-fold higher prevalence of infertility, compared with women without PCOS, independent of body mass index (BMI). A healthy lifestyle is recommended to improve overall health and fertility in PCOS but there is limited evidence on the isolated effects of exercise, especially for reproductive outcomes. Previous findings indicate superior metabolic health benefits after vigorous compared with moderate-intensity exercise. Our primary aim is to determine the effect of high-intensity interval training (HIT) on menstrual frequency, as a proxy of reproductive function, in women with PCOS.; Methods and Analysis: The study is a two-centre, randomised, controlled trial with three parallel groups. Women (n=64) from Trondheim (Norway) and Melbourne (Australia) with PCOS according to the Rotterdam criteria will be randomly allocated (1:1:1) to high-volume HIT, low-volume HIT or a control group with no exercise after stratifying for BMI < or ≥ 27 kg/m 2 and study centre. Measurements for study end points will be undertaken at baseline, after a 16 week exercise intervention and at 12 months following baseline assessments. The primary outcome measure is menstruation frequency, measured as the number of self-reported menstrual bleedings divided by the number of expected menstrual bleedings during a 12-month period. Secondary outcome measurements include markers of cardiovascular, metabolic and reproductive health, as well as quality of life and adherence to and enjoyment of exercise.; Ethics and Dissemination: The Regional Committee Medical Research Ethics, Norway, and The Australian Catholic University Human Research Ethics Committee, Australia, have approved the trial protocol. This trial will provide new insight regarding the impact of exercise on fertility in PCOS. We expect this trial to contribute to new therapeutic exercise strategies as part of clinical care for women with PCOS.; Trial Registration Number: Clinical trial gov NCT02419482.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Kietpeerakool, C., et al. (2019). "Management of drainage for malignant ascites in gynaecological cancer." The Cochrane Database of Systematic Reviews 12: CD007794.
	Background: Ascites is the accumulation of fluid within the abdominal cavity. Most women with advanced ovarian cancer and some women with advanced endometrial cancer need repeated drainage for ascites. Guidelines to advise those involved in the drainage of ascites are usually produced locally and are generally not evidence-based. Managing drains that improve the efficacy and quality of the procedure is key in making recommendations that could improve the quality of life (QoL) for women at this critical period of their lives.; Objectives: To evaluate the effectiveness and adverse events of different interventions for the management of malignant ascites drainage in the palliative care of women with gynaecological cancer.; Search Methods: We searched CENTRAL, MEDLINE, and Embase to 4 November 2019. We checked clinical trial registries, grey literature, reports of conferences, citation lists of included studies, and key textbooks for potentially relevant studies.; Selection Criteria: We included randomised controlled trials (RCTs) of women with malignant ascites with gynaecological cancer. If studies also included women with non-gynaecological cancer, we planned to extract data specifically for women with gynaecological cancers or request the data from trial authors. If this was not possible, we planned to include the study only if at least 50% of participants were diagnosed with gynaecological cancer.; Data Collection and Analysis: Two review authors independently selected studies, extracted data, evaluated the quality of the included studies, compared results, and assessed the certainty of the evidence using Cochrane methodology.; Main Results: In the original 2010 review, we identified no relevant studies. This updated review included one RCT involving 245 participants that compared abdominal paracentesis and intraperitoneal infusion of catumaxomab versus abdominal paracentesis alone. The study was at high risk of bias in almost all domains. The data were not suitable for analysis. The median time to the first deterioration of QoL ranged from 19 to 26 days in participants receiving paracentesis alone compared to 47 to 49 days among participants receiving paracentesis with catumaxomab infusion (very low-certainty evidence). Adverse events were only reported among participants receiving catumaxomab infusion. The most common severe adverse events were abdominal pain and lymphopenia (157 participants; very low-certainty evidence). There were no data on the improvement of symptoms, satisfaction of participants and caregivers, and cost-effectiveness.; Authors' Conclusions: Currently, there is insufficient evidence to recommend the most appropriate management of drainage for malignant ascites among women with gynaecological cancer, as there was only very low-certainty evidence from one small RCT at overall high risk of bias. (Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Kim, A., et al. (2021). "Preoperative MRI and LDH in women undergoing intra-abdominal surgery for fibroids: Effect on surgical route." PloS One 16(2): e0246807.
	Introduction: Our institution implemented a preoperative protocol to identify high-risk cases for which power morcellation should be avoided.; Material and Methods: In this retrospective cohort study, an institutional protocol requiring preoperative Magnetic Resonance Imaging with diffusion-weighted imaging and serum Lactate Dehydrogenase levels was implemented. Chart review was performed including all women who underwent intra-abdominal surgery for symptomatic fibroids from 4/23/2013 to 4/23/2015.; Results: A total of 1,085 women were included, 479 before and 606 after implementation of the Magnetic Resonance Imaging / Lactate Dehydrogenase protocol. The pre-protocol group had more post-menopausal women (4% vs. 2%, p = 0.022) and women using tamoxifen (2% vs. 0%, p = 0.022) than those in the post-protocol group, but baseline patient characteristics were otherwise similar between groups. Incidence of malignant pathological diagnoses did not change significantly over the time period in relation to protocol implementation. The rate of open surgery for both hysterectomy and myomectomy remained the same in the year preceding and the year following initiation of the protocol (open hysterectomy rate was 19% vs. 16% in pre- and post-protocol groups, respectively, P = 0.463, and open myomectomy rate was 10% vs. 9% rates in pre- and post-protocol groups, respectively, P = 0.776). There was a significant decrease in the use of power morcellation (66% in pre- and 50% in post-protocol cohorts, p<0.001) and an increased use of containment bags (1% in pre- and 19% in post-protocol cohort). When analyzing the subset of women who had abnormal Magnetic Resonance Imaging / and Lactate Dehydrogenase results, abnormal Magnetic Resonance Imaging results alone resulted in higher rates of open approach (65% for abnormal vs. 35% for normal). Similarly, a combination of abnormal Magnetic Resonance Imaging and Lactate Dehydrogenase tests resulted in higher rates of open approach (70% for abnormal and 17% for normal). Abnormal Lactate Dehydrogenase results alone did not influence route.; Conclusions: Rates of MIS procedures were decreased for women with abnormal preoperative Magnetic Resonance Imaging results. False positive results appear to be one of the main drivers for the use of an open surgical route.; Competing Interests: The authors have declared that no competing interests exist.

Kim, A., et al. (2019). "Clinical outcome of single-incision slings, excluding TVT-Secur, vs standard slings in the surgical management of stress incontinence: an updated systematic review and meta-analysis." BJU International 123(4): 566-584.
	The aim of the present paper was to assess and compare the long-term efficacy and safety of single-incision mini-slings (SIMSs), except tension-free vaginal tape (TVT)-Secur, with standard midurethral slings (SMUSs) for female stress urinary incontinence through an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing these two surgical methods. A literature review of all RCTs comparing SIMSs (Mini-Arc, Contasure-Needleless, Ophira, Tissue Fixation System and Ajust), except TVT-Secur, with SMUSs was performed. The Medline, Embase, Scopus, Web of Science and Cochrane Controlled Trial Register databases were reviewed. We retrieved 29 RCTs (including a total of 2 986 patients) that compared SIMSs, except TVT-Secur, with SMUSs. Meta-analysis of long-term results showed no significant difference in the patient-reported cure rate (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.60); however, we found that SMUSs had a significantly superior objective cure rate (OR 0.68, 95% CI 0.47-0.99; P = 0.04). SIMSs were associated with a significantly shorter operation time, lower immediate postoperative pain based on a visual analogue scale score, lower intra-operative blood loss, and lower postoperative voiding dysfunction. The meta-analysis showed clear evidence of the superiority of SMUSs over SIMSs, except TVT-Secur, in terms of the objective cure rate, after long-term follow-up; however, SIMSs were superior with respect to immediate postoperative pain, intra-operative blood loss, and postoperative voiding dysfunction.Copyright © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd

Kim, B., et al. (2022). "Effect of smartphone app-based health care intervention for health management of high-risk mothers: a study protocol for a randomized controlled trial." Trials 23(1): 486.
	Background: The 4th Industrial Revolution with the advent of the smart era, in which artificial intelligence, such as big data analysis and machine learning, is expected, and the provision of healthcare services using smartphones has become a reality. In particular, high-risk mothers who experience gestational diabetes, gestational hypertension, and prenatal and postpartum depression are highly likely to have adverse effects on the mother and newborn due to the disease. Therefore, continuous observation and intervention in health management are needed to prevent diseases and promote healthy behavior for a healthy life.; Methods: This randomized controlled trial will provide mothers 18 years of age or older with health care information collected based on evidence-based literature data using a smartphone app for 6 weeks. About 500 mothers will be selected in consideration of the dropout rate due to the characteristics of mothers. The study group and control group will be computer-generated in a 1:1 ratio through random assignment. The research group will receive health management items through the app, and health management information suitable for the pregnancy cycle is pushed to an alarm. The control group will receive the health management information of the paper. We also followed the procedure for developing mobile apps using the IDEAS framework.; Discussion: These results show the effectiveness of smart medical healthcare services and promote changes in health behaviors throughout pregnancy in high-risk mothers.; Trial Registration: Clinical trial registration information for this study has been registered with WHO ICTRP and CRIS (Korea Clinical Research Information Service, CRIS). Clinical trial registration information is as follows: Study of development of integrated smart health management service for the whole life cycle of high-risk mothers and newborns based on community, KCT0007193 . Registered on April 14, 2022, prospectively registered. This protocol version is Version 1.0. April 14, 2022. (© 2022. The Author(s).)

Kim, C., et al. (2023). "The role of postoperative radiation after radical hysterectomy for women with early-stage neuroendocrine carcinoma of the cervix: A meta-analysis." Gynecologic Oncology 170: 328-332.
	Introduction: Neuroendocrine carcinoma of the cervix (NECC) is an aggressive disease with high rates of nodal disease spread even in seemingly cervix-confined disease. Many providers routinely prescribe postoperative radiation therapy in an effort to reduce recurrences despite a lack of supporting studies. The objective of this study was to determine recurrence and mortality in patients with early-stage NECC who had pelvic radiation after radical hysterectomy compared to those who did not receive radiation.; Methods: We performed a meta-analysis of 13 unique studies that reported recurrence and/or mortality for patients with early-stage NECC who underwent radical hysterectomy with or without adjuvant radiation therapy.; Results: In 5 studies that reported overall recurrence rates, 63 (52.5%) of 120 patients who received postoperative radiation recurred compared to 70 (37.8%) of 185 patients who did not (RR 1.21, 95% CI: 0.85-1.70, p = 0.29). In 5 studies that reported pelvic recurrence rates, there were 15 pelvic recurrences (12.5%) in the 120 patients who received postoperative radiation compared to 45 pelvic recurrences (24.3%) in the 185 patients who did not (RR 0.60, 95% CI: 0.34-1.08, p = 0.09). In 13 studies that reported mortality rate, there were 138 deaths (34.8%) in 396 patients who received postoperative radiation therapy compared to 223 (35.2%) in 632 patients who did not (RR 1.08, 95% CI: 0.75-1.56, p = 0.66).; Conclusions: The addition of routine postoperative radiation therapy in all patients with early-stage NECC after radical hysterectomy may reduce pelvic recurrences but does not appear to decrease overall recurrence or death. However, there may still be a role for postoperative radiation therapy in patients with additional high-risk pathologic factors.; Competing Interests: Declaration of Competing Interest Michael Frumovitz receives research funding from AkesoBio and GlaxoSmithKline and serves on speaker and advisory boards for Stryker. All other authors have no disclosures. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Kim Gun, H., et al. (2022). "Ultrasound-guided sclerotherapy for the treatment of ovarian endometrioma: an updated systematic review and meta-analysis." European radiology 32(3): 1726-1737.
	Objective: To determine the efficacy and safety of ultrasound (US)-guided sclerotherapy for the treatment of ovarian endometrioma through a systematic review and meta-analysis.; Methods: MEDLINE and EMBASE databases were searched for studies reporting outcomes in patients with endometrioma who were treated with US-guided sclerotherapy. Meta-analyses of recurrence, pain resolution, pregnancy, technical success, and complication rates were analyzed. Subgroup analyses were conducted regarding the indwelling time of sclerotherapy (≤ 10 min vs > 10 min).; Results: Twenty-eight studies (1301 patients) were included. The pooled technical efficacy was 98.3%. The pooled estimates of recurrence, pain resolution, and pregnancy rate were 13.8%, 85.9%, and 37.6%, respectively. The pooled major complication rate was 1.7%. A sclerotherapy time > 10 min had a lower pooled recurrence rate than a time ≤ 10 min (11.2% vs 20.9%; p = 0.106). Direct comparisons showed that the recurrence rate was significantly lower with sclerotherapy > 10 min than with sclerotherapy ≤ 10 min (OR, 0.2; p = 0.015). Regarding pregnancy rates, sclerotherapy of > 10 min showed no significant difference compared with sclerotherapy of ≤ 10 min (35.9% vs 38.8%; p = 0.664). Direct comparisons with surgery showed that sclerotherapy increased the pregnancy rate compared with surgery (OR, 2.0; p = 0.042). There was no significant difference in AMH level before and after sclerotherapy (p = 0.951). There was no significant difference in major complication rates between sclerotherapy > 10 min and ≤ 10 min (p = 0.837).; Conclusion: US-guided sclerotherapy seems to be an effective and safe therapeutic option regarding recurrence, pain resolution, and pregnancy for patients with ovarian endometrioma.; Key Points: • US-guided sclerotherapy seems to be an effective and safe therapeutic option regarding recurrence, pain resolution, and pregnancy for patients with ovarian endometrioma. • Sclerotherapy of more than 10 min had a lower recurrence rate than sclerotherapy less than or equal to 10 min. There was no significant difference in major complication rates between sclerotherapy of > 10 min and ≤ 10 min. • Future randomized controlled trials are warranted to compare the outcomes of US-guided sclerotherapy with surgery. (© 2021. European Society of Radiology.)

Kim, J., et al. (2023). "Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis." Infection & chemotherapy.
	BACKGROUND: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. MATERIALS AND METHODS: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). RESULTS: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. CONCLUSION: Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Kim, J., et al. (2021). "Stage 2 acupuncture for poor ovarian response: a randomized controlled trial." Journal of Clinical Medicine 10(10).
	Acupuncture is believed to improve ovarian reserve and reproductive outcomes in women undergoing in vitro fertilization (IVF). This study was conducted to evaluate the effect of network‐optimized acupuncture followed by IVF on the oocyte yield in women showing a poor ovarian response. This study was an exploratory randomized controlled trial conducted from June 2017 to January 2020 at the Pusan National University Hospital. Women diagnosed with poor ovarian response were enrolled and randomly divided into two groups: IVF alone and Ac + IVF groups (16 acupuncture sessions before IVF treatment). Eight acupoints with high degree centrality and betweenness centrality were selected using network analysis. Among the participants, compared with the IVF treatment alone, the acupuncture + IVF treatment significantly increased the number of retrieved mature oocytes in women aged more than 37 years and in those undergoing more than one controlled ovarian hyperstimulation cycle. The negative correlation between the number of retrieved mature oocytes and consecutive controlled ovarian hyperstimulation cycles was not observed in the Ac + IVF group irrespective of the maternal age. These findings suggest that physicians can consider acupuncture for the treatment of women with poor ovarian response and aged > 37 years or undergoing multiple IVF cycles.

Kim, J. H., et al. (2023). "Impact of postoperative residual disease on survival in epithelial ovarian cancer with consideration of recent frontline treatment advances: A systematic review and meta-analysis." Gynecologic Oncology 179: 24-32.
	Background: Current treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment. Method(s): We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on progression-free survival (PFS) and OS, we constructed a linear regression model for log-transformed median PFS and OS. Patients who did or did not receive first-line maintenance therapy were examined. Result(s): A total of 97 trials with 43,260 patients were included:2476 received poly(ADP-ribose) polymerase (PARP) inhibitors and 6587 received bevacizumab. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independent of the use of systemic maintenance. In the subgroup analysis of patients receiving maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increase of 19.13% for every 10% increase in complete cytoreduction rates. Conclusion(s): Total macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction, even after the introduction of recent advances in frontline treatment for EOC.Copyright © 2023 Elsevier Inc.

Kim Ji, H., et al. (2022). "Quality of life outcomes from the randomized trial of hyperthermic intraperitoneal chemotherapy following cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01)." Journal of Gynecologic Oncology 33(4): e54.
	Objective: To investigate the health-related quality of life (HRQOL) related to hyperthermic intraperitoneal chemotherapy (HIPEC) following primary or interval cytoreductive surgery for primary ovarian cancer.; Methods: Between 2010 and 2016, a total of 184 patients were randomly assigned to receive cytoreductive surgery with HIPEC (n=92) or without HIPEC (n=92). Quality of life (QOL) assessment was evaluated at baseline (before surgery); on postoperative day 7; after the 3rd and 6th cycle of adjuvant chemotherapy; and at 3, 6, 9, and 12 months after randomization. Patient-reported QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC-QLQ-C30), ovarian cancer questionnaire modules (QLQ-OV28), and the MD Anderson Symptoms Inventory (MDASI).; Results: Of the 184 patients enrolled, 165 (83/92 in the HIPEC group and 82/92 in the control group) participated in the baseline QOL assessment. There were no statistically significant differences in functional scales and symptom scales in QLQ-C30; symptom scales, including gastrointestinal symptoms QLQ-OV28; and severity and impact score in MDASI between the 2 treatment groups until 12 months after randomization.; Conclusion: HIPEC with cytoreductive surgery showed no statistically significant difference in HRQOL outcomes. Thus, implementation of HIPEC during either primary or interval cytoreductive surgery does not impair HRQOL.; Trial Registration: ClinicalTrials.gov Identifier: NCT01091636.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Kim Ji, H., et al. (2023). "Impact of warm saline irrigation, hyperthermic intraperitoneal chemotherapy on postoperative pain in primary ovarian cancer from the KOV-HIPEC-01 randomized trial." Gynecologic Oncology 177: 32-37.
	Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a treatment option at the time of cytoreductive surgery after neoadjuvant chemotherapy. The effect of active warming of HIPEC on postoperative pain needs to be investigated. This study aimed to investigate whether HIPEC reduces postoperative pain.; Methods: From the KOV-HIPEC-01 trial, a randomized controlled trial of HIPEC for advanced primary ovarian cancer, 184 patients with a residual tumor size <1 cm were randomly assigned to the HIPEC and control groups at a 1:1 ratio. The consumption of analgesics and pain scales were analyzed. Hyperthermic intraperitoneal chemotherapy was administered after cytoreductive surgery. The primary objective was to compare the consumption of opioids measured in morphine milligram equivalents and non-opioids measured as the maximum daily dose between the HIPEC and control groups. The secondary objective was to compare the minimum and maximum pain intensities on numeric rating scales between the two groups using a linear mixed model.; Results: Lesser consumption of non-opioids, with a lower mean maximum daily dose on postoperative days 1 and 2, was observed. The HIPEC group also experienced lower maximum pain intensities on postoperative day 1. No overall differences in the minimum or maximum pain intensities were observed on postoperative day 7.; Conclusion: The addition of HIPEC to cytoreductive surgery did not lead to increased postoperative pain, as demonstrated by a reduction in the use of analgesics and lower scores on postoperative pain scales during the early postoperative period.; Competing Interests: Declaration of Competing Interest Dr. Lim reported having a consulting or advisory role for AstraZeneca, Boryung, CKD Pharm, Genexine, Hospicare, GI Innovation, and Takeda and receiving research funding from AbbVie, Amgen, Astellas, AstraZeneca, BeiGene, Cellid, CKD Pharm, Clovis, Eisai, Genexine, GSK, Incyte, Merck, MSD, OncoQuest, Pfizer, and Roche outside the submitted work. Dr. S-Y Park reported having a consulting or advisory role for Boryung and Takeda and receiving research funding from AbbVie, Amgen, Astellas, AstraZeneca, BeiGene, Cellid, CKD Pharm, Clovis, Eisai, Genexine, GSK, Incyte, Merck, MSD, OncoQuest, Pfizer, and Roche outside the submitted work. No other disclosures were reported. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Kim, J. W. and S. I. Kim (2023). "SY05-5 Clinical trials for advanced or recurrent cervical cancer." Annals of Oncology 34(Supplement 3): S1358.
	As the fourth most frequently diagnosed disease and the fourth most significant cause of cancer deaths in women, cervical cancer is a burden for the entire world. Systemic therapies for advanced or recurring cervical cancer have long been stuck in a deadlock, but recent advancements have been made thanks to the application of new therapeutics. Based on phase II KEYNOTE-158, the FDA approved pembrolizumab in 2018 for PD-L1-positive advanced cervical cancer that progressed during or after chemotherapy, and pembrolizumab in combination with chemotherapy, with or without bevacizumab, in 2021 for PD-L1-positive recurrent or metastatic cervical cancer. A tissue factor-directed antibody-drug combination called tisotumab vedotin has also been authorized to treat cervical cancer that has returned or spread and is progressing during or after chemotherapy, based on phase II InnovaTV 204/GOG-3023/ENGOT-cx6. The hunt for improved systemic therapy alternatives is still ongoing. In recurrent or metastatic cervical cancer, the phase III ENGOT-Cx10/GOG-3030/BEATcc study examined chemotherapy plus bevacizumab with or without atezolizumab. Phase II GOG-3028/RaPiDS evaluates anti-PD-1 monotherapy against anti-CTLA4 combination therapy for cervical cancer that progressed following platinum-based first-line treatment. High-risk patients with locally advanced cervical cancer are randomly assigned to receive chemoradiation (CRT) with or without pembrolizumab in phase III ENGOT-Cx11/KEYNOTE-A18. In addition to systemic therapy, surgical trials are also ongoing. The PAROLA trial by GINECO/ENGOT examines whether para-aortic lymphadenectomy before CRT lowers the recurrence rate in stage IIIC1r cervical cancer. In stage IIICr cervical cancer, the phase III KGOG-1047/DEBULK study examines the therapeutic impact of surgically removing metastatic lymph nodes. To sum up, positive results from clinical studies will enable an ideal treatment plan.Copyright © 2023

Kim, J. Y., et al. (2023). "Combined Hyperthermia and Re-Irradiation in Non-Breast Cancer Patients: A Systematic Review." Cancers 15(3): 742.
	Purpose: This systematic literature review summarizes clinical studies and trials involving combined non-ablative hyperthermia and re-irradiation in locoregionally recurrent cancer except breast cancer. Method(s): One database and one registry, MEDLINE and clinicaltrials.gov, respectively, were searched for studies on combined non-ablative hyperthermia and re-irradiation in non-breast cancer patients. Extracted study characteristics included treatment modalities and re-irradiation dose concepts. Outcomes of interest were tumor response, survival measures, toxicity data and palliation. Within-study bias assessment included the identification of conflict of interest (COI). The final search was performed on 29 August 2022. Result(s): Twenty-three articles were included in the final analysis, reporting on 603 patients with eight major tumor types. Twelve articles (52%) were retrospective studies. Only one randomized trial was identified. No COI statement was declared in 11 studies. Four of the remaining twelve studies exhibited significant COI. Low study and patient numbers, high heterogeneity in treatment modalities and endpoints, as well as significant within- and across-study bias impeded the synthesis of results. Conclusion(s): Outside of locoregionally recurrent breast cancer, the role of combined moderate hyperthermia and re-irradiation can so far not be established. This review underscores the necessity for more clinical trials to generate higher levels of clinical evidence for combined re-irradiation and hyperthermia.Copyright © 2023 by the authors.

Kim, K., et al. (2021). "Modulated electro-hyperthermia with weekly paclitaxel or cisplatin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: The KGOG 3030 trial." Experimental and Therapeutic Medicine 22(1): 787.
	The present study (KGOG 3030) aimed to evaluate the safety of modulated electro-hyperthermia (mEHT) therapy with weekly administration of paclitaxel or cisplatin in female patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. A total of 12 patients were randomized into the paclitaxel or cisplatin arm at a 1:1 ratio. Patients received weekly administration of paclitaxel (70 mg/m2) or cisplatin (40 mg/m2) intravenously on days 1, 8 and 15, and underwent mEHT therapy for 1 h on days 1, 4, 8, 11, 15, 18, 21 and 24 for each 4-week cycle. The primary endpoint was the occurrence of dose-limiting toxicity (DLT). The secondary endpoints were treatment-emergent adverse events (TEAEs), objective response rate, carbohydrate antigen 125 (CA125) response rate, progression-free survival (PFS) and overall survival (OS). In total, 16 patients were recruited, but four patients dropped out. None of the 12 remaining patients (6 each in the two arms) experienced DLT. Overall, 0 and 4 grade 3 TEAEs (anemia, nausea, neutrophil count decreased and platelet count decreased) occurred in the paclitaxel and cisplatin arm, respectively. Furthermore, one confirmed partial response and two CA125 responses were observed in the cisplatin arm. The median PFS time in the paclitaxel and cisplatin arms was 3.0 months (range, 1.7-4.6 months) and 6.8 months (range, 3.9-11.8 months), respectively, while the median OS time was 11.5 months (range, 8.4-28.8+ months) and not reached (range, 3.9-38.5+ months), respectively. In conclusion, mEHT therapy with weekly paclitaxel or cisplatin appeared safe and warrants further investigation. The present trial was registered with www.clinicaltrials.gov on January 22, 2015 (trial registration no. NCT02344095).

Kim Nae, R., et al. (2022). "Minimally invasive surgery versus open surgery in high-risk histologic endometrial cancer patients: A meta-analysis." Gynecologic Oncology 166(2): 236-244.
	Objective: To compare the effects of minimally invasive surgery (MIS) and open surgery (OPS) on the risk of recurrence and mortality in patients with endometrial cancer (EC) of high-risk histology (grade 3 endometrioid adenocarcinoma, papillary serous carcinoma [PS], clear cell carcinoma [CC], and carcinosarcoma) using meta-analysis.; Material and Methods: We systematically reviewed published studies comparing MIS and OPS in EC patients with high-risk histology until January 2022. The endpoints were recurrence and mortality rate. Study design features that may have affected participant selection, recurrence/death detection, and manuscript publication were assessed. For pooled estimates of the effect of MIS on recurrence/mortality, the random- or fixed-effects meta-analytical models were used after assessing the cross-study heterogeneity.; Result: Nine observational studies (eight retrospective and one prospective) fulfilled our search criteria (MIS, 8877 patients; OPS, 5751 patients). The fixed-effects model-based meta-analysis indicated that MIS did not significantly increase the risk of recurrence (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.71-1.05; p = 0.13) and mortality (HR, 0.86; 95% CI, 0.79-0.93; p < 0.001) when compared with OPS. This pattern was also observed in the subgroup analyses based on the stage (early stage vs. all stage), histology (PS and CC), and MIS type (laparoscopy vs. robotic). There was no evidence of publication bias.; Conclusion: This meta-analysis of observational studies revealed that MIS did not compromise the prognosis of EC patients with high-risk histology. Well-designed randomized controlled trials could verify the results of this uncommon but deadly tumor. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Kim, S., et al. (2023). "The effects of music therapy on the psychological status of women with perimenopause syndrome." Menopause (New York, N.Y.) 30(10): 1045-1052.
	Objective: Women experience many physical and psychological changes with the reduction of progesterone and estrogen as ovarian function gradually weakens. This study applied a music psychotherapy program as a nonpharmacological treatment method in addition to treatment using drugs such as hormone therapy for perimenopausal women.; Method: This study's pre-post, control-experimental research compared 20 women in the music psychotherapy experimental group and 20 in the cognitive behavioral therapy (CBT) control group. The perimenopausal women aged between 40 and 60 years experienced no menstrual period for 1 year. We provided eight sessions of music psychotherapy, including CBT, each lasting 60 minutes. The study period was 4 months from the time of recruitment.; Results: The music therapy group showed a more significant decrease in the Menopause Rating Scale total (change over time, 9.2 points and 3.5 points, respectively; P = 0.008) and psychology subcategory (change over time, 6.5 points and 0.9 points, respectively; P = 0.004) of Menopause Rating Scale scores, compared with the CBT group. In addition, the music therapy group increased their quality of life psychological score, but the CBT group did not.; Conclusions: These results suggest that music therapy can help the psychological and emotional symptoms of perimenopausal women and is effective for treatment. The study result provides a therapeutic basis for developing treatments for nonpharmacological mediation.; Competing Interests: Financial disclosure/conflicts of interest: None reported. (Copyright © 2023 by The Menopause Society.)

Kim, S., et al. (2023). "A Randomized, Multicenter, Double-Blind, Parallel, Non-Inferiority Clinical Study to Compare the Efficacy and Safety of Unicenta and Melsmon for Menopausal Symptom Improvement." Medicina (Kaunas, Lithuania) 59(8).
	This study was conducted to evaluate the efficacy and safety of Unicenta in female subjects with menopausal symptoms by analyzing the changes in the Kupperman index (primary endpoint) and hormonal changes (secondary endpoint). It was a randomized, multi-center, double-blind, parallel, non-inferiority clinical study conducted at two different tertiary medical centers. A Unicenta injection was shown to be non-inferior to Melsmon based on the Kupperman index in both the intent-to-treat and per-protocol populations ( p = 0.789 and p = 0.826, respectively). Additionally, there were no statistically significant differences in hormone levels (estradiol, follicular-stimulating hormone) or in the evaluation of facial flushes. There was no statistically significant difference in the incidence rate of adverse events between the two groups ( p = 0.505). The study demonstrated that Unicenta is not inferior to Melsmon in terms of the change in the Kupperman index after 12 days of injection. The efficacy and safety of Unicenta were shown, resulting in the improvement of menopausal symptoms.

Kim, S.-D. (2019). "Yoga for menstrual pain in primary dysmenorrhea: A meta-analysis of randomized controlled trials." Complementary Therapies in Clinical Practice 36: 94-99.
	Objectives: To assess the overall effect size of the impact of yoga on menstrual pain in primary dysmenorrhea.; Methods: Randomized controlled trials that were published in the English language until December 2018 in PubMed, EMBASE, Web of Science, and the Cochrane Library electronic databases were searched. The methodologies from 4 trials conducted on 230 participants with primary dysmenorrhea were included in this meta-analysis to compare the effects that performing a yoga program has on menstrual pain (n = 129) to the effects of not performing yoga (n = 101).; Results: The overall effect size of the impact of a yoga program on menstrual pain in primary dysmenorrhea was high with a standardized mean difference of -2.09 (-3.99 to -0.19) (p = 0.031) among the effect sizes of the 4 trials (95% confidence interval).; Conclusions: Yoga is an effective intervention for alleviating menstrual pain in women with primary dysmenorrhea. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Kim Se, I., et al. (2019). "Selection of patients with ovarian cancer who may show survival benefit from hyperthermic intraperitoneal chemotherapy: A systematic review and meta-analysis." Medicine 98(50): e18355.
	Background: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis from various malignancies. However, the effectiveness of HIPEC for ovarian cancer is still controversial. Therefore, we performed this meta-analysis to identify patients with ovarian cancer who can obtain survival benefit from HIPEC.; Methods: Articles regarding HIPEC in the MEDLINE, EMBASE, and Cochrane Library were searched till December 2018. In total, 13 case-control studies and two randomized controlled trials were included in this meta-analysis. We investigated the effect of HIPEC on disease-free survival (DFS) and overall survival (OS), and performed subgroup analyses based on the study design, adjustment of confounding variables, and quality of the study.; Results: HIPEC improved both DFS (hazard ratio [HR], 0.603; 95% confidence interval [CI], 0.513-0.709) and OS (HR, 0.640; 95% CI, 0.519-0.789). In cases of primary disease, HIPEC improved DFS (HR, 0.580; 95% CI, 0.476-0.706) and OS (HR, 0.611; 95% CI, 0.376-0.992). Subgroup analyses revealed that HIPEC did not improve OS but improved DFS of patients with residual tumors ≤1 cm or no visible tumors. In cases of recurrent disease, HIPEC was associated with better OS (HR, 0.566; 95% CI, 0.379-0.844) but not with DFS. Subgroup analyses also revealed similar tendencies. However, HIPEC improved DFS of patients with residual tumors ≤1 cm or no visible tumors, while it improved OS of only those with residual tumors ≤1 cm.; Conclusions: HIPEC may improve DFS of patients with ovarian cancer when residual tumors were ≤1 cm or not visible. It may also improve OS of only patients with recurrent disease whose residual tumors were ≤1 cm.

Kim, S. H., et al. (2023). "Effect of analgesia nociception index monitor-based nociception control on perioperative stress responses during laparoscopic surgery in Trendelenburg position: a randomized controlled trial." Frontiers in Medicine 10: 1196153.
	Introduction: The analgesia nociception index (ANI) monitor is a nociception monitoring device based on heart rate variability. We aimed to determine the effect of ANI monitor-based intraoperative nociception control on the perioperative stress response during laparoscopic surgery in the Trendelenburg position. Method(s): Altogether, 72 female patients who underwent total laparoscopic hysterectomy were randomized to either the control or ANI group. Intraoperative nociception was controlled by remifentanil administration in a conventional manner (based on blood pressure and heart rate) in the control group and by ANI monitoring in the ANI group. Perioperative stress responses were estimated by measuring the levels of serum catecholamines and catabolic stress hormones at three timepoints: after loss of consciousness, at the end of surgery, and 1 h after the end of surgery. Result(s): The serum cortisol level at the end of surgery was significantly higher in the ANI group than in the control group (p < 0.001), although more remifentanil was administered in the ANI group than in the control group (p < 0.001). Changes in the other estimators' levels were comparable between groups during the perioperative period. The hemodynamic profiles during surgery were also significantly different between the two groups. Phenylephrine use to treat hypotension was more common in the ANI group than in the control group (p = 0.005). However, postoperative clinical outcomes such as pain and nausea/vomiting did not differ between groups. Conclusion(s): ANI monitor-based nociception control in laparoscopic surgery in the Trendelenburg position did not improve perioperative stress responses, intraoperative opioid consumption, or postoperative clinical outcomes. Clinical trial registration: ClinicalTrials.gov (NCT04343638).Copyright © 2023 Kim, Chang, Lee, Seo, Kwon and Lee.

Kim, S. I., et al. (2022). "Impact of bevacizumab and secondary cytoreductive surgery on survival outcomes in platinum-sensitive relapsed ovarian clear cell carcinoma: A multicenter study in Korea." Gynecologic Oncology 166(3): 444-452.
	Objective: This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. Method(s): OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS). Result(s): 138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P < 0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P < 0.001) and OS (P < 0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P < 0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery. Conclusion(s): The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.Copyright © 2022 Elsevier Inc.

Kim, S. I., et al. (2022). "A MULTICENTER STUDY OF NIRAPARIB MAINTENANCE THERAPY IN BRCA WILD-TYPE, NEWLY DIAGNOSED ADVANCED OVARIAN CANCER: POLO TRIAL." International Journal of Gynecological Cancer 32(Supplement 3): A236-A237.
	Objectives The POLO trial aims to investigate the efficacy of niraparib maintenance therapy in patients with BRCA wildtype, newly diagnosed advanced ovarian cancer who are not at high risk of recurrence. Methods The POLO is a multi-center, investigator-initiated, single-arm, phase IV trial of patients with FIGO stage III-IV high-grade serous or high-grade endometrioid ovarian cancer. This study includes patients having both germline and somatic wild-type BRCA1/2 genes, no visible residual tumor after primary cytoreductive surgery, and responses to the postoperative platinum-based combination chemotherapy. Meanwhile, patients who received neoadjuvant chemotherapy are excluded. All enrolled patients are treated with niraparib maintenance therapy for three years or until disease progression, unacceptable toxicity, or withdrawal of patient consent. Results The primary endpoint of this trial is the 12-month progression-free survival (PFS) rate. The secondary endpoints are overall survival, PFS, time to first subsequent treatment, time to second progression (PFS2), time to the second subsequent treatment, and safety. All patients should provide tumor slides obtained during cytoreductive surgery, for a prospective examination of somatic homologous recombination deficiency (HRD) and homologous recombination repair gene alterations. Pre- and post-niraparib (at the time of disease progression if available) blood samples will be collected for circulating cellfree DNA analyses. Molecular biomarkers that may indicate clinical response/resistance to niraparib will be identified. Conclusions In total, 102 patients will be recruited from five sites. An interim analysis is planned after recruitment of 68 participants. Accrual is expected to be completed in 2024, followed by presentation of results in 2025.

Kim Soyoun, R., et al. (2022). "Enhanced recovery after minimally invasive gynecologic oncology surgery to improve same day discharge: a quality improvement project." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(4): 457-465.
	Objectives: Same day discharge after minimally invasive hysterectomy has been shown to be safe and feasible. We designed and implemented a quality improvement perioperative program based on early recovery after surgery principles to improve the rate of same day discharge from 30% to 75% after minimally invasive gynecologic oncology surgery over a 12 month period.; Methods: We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12 month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison of clinicodemographic variables and perioperative outcomes. A multidisciplinary team developed a comprehensive perioperative care program and followed quality improvement methodology. Patients were followed up for 30 days after discharge. A statistical process chart was used to monitor the effects of our interventions, and a multivariate analysis was conducted to determine factors associated with same day discharge.; Results: Same day discharge rate increased from 29% to 75% after implementation (p<0.001). The post-intervention cohort was significantly younger (59 vs 62 years; p=0.038) and had shorter operative times (180 vs 211 min; p<0.001) but the two groups were similar in body mass index, comorbidity, stage, and intraoperative complications. There was no difference in 30 day perioperative complications, readmissions, reoperations, emergency department visits, or mortality. Overnight admissions were secondary to nausea and vomiting (16%), complications of pre-existing comorbidities (12%), and urinary retention (8%). On multivariate analysis, longer surgery, timing of surgery, and narcotic use on the ward were significantly associated with overnight admission. Overall, 89% of patients rated their experience as 'very good' or 'excellent', and 87% felt that their length of stay was adequate.; Conclusions: Following implementation of a perioperative quality improvement program targeted towards minimally invasive gynecologic oncology surgery, our intervention significantly improved same day discharge rates while maintaining a low 30 day perioperative complication rate and excellent patient experience.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Kim, S. R., et al. (2022). "Implementation of a standardized voiding protocol after minimally invasive surgery: A quality improvement initiative." International Journal of Gynecology and Obstetrics 159(3): 696-701.
	Objectives: To assess the effects of the implementation of a standardized voiding protocol in patients undergoing minimally invasive hysterectomy at a single cancer center in terms of the urinary tract infection (UTI) rate, time to first void, and overnight stays secondary to urinary retention. Method(s): We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12-month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison. A multidisciplinary team developed and implemented a standardized voiding protocol using quality improvement methodology. We compared the demographics, time to first void, rate of urinary retention, and UTI rates between the pre- and post-intervention cohorts. Result(s): Our intervention led to a significant reduction in the time to first void (289 min vs. 566 min; P < 0.001), rate of urinary retention (2% vs. 10%; P = 0.015), and postoperative UTI (4% vs. 8%; P = 0.249). There was a similar rate of patients going home with a Foley catheter (9% vs. 11%; P = 0.850). Conclusion(s): Implementation of a standardized voiding protocol was associated with a reduction in rate of UTI, time to first void, and overnight stays secondary to urinary retention.Copyright © 2022 International Federation of Gynecology and Obstetrics.

Kim Su, H., et al. (2022). "Acute progesterone feedback on gonadotropin secretion is not demonstrably altered in estradiol-pretreated women with polycystic ovary syndrome." Physiological reports 10(7): e15233.
	Women with polycystic ovary syndrome (PCOS) demonstrate gonadotropin-releasing hormone (GnRH) pulse generator resistance to suppression with 7 days of progesterone and estradiol administration. It remains unknown whether such women demonstrate impairments in acute progesterone negative feedback on LH pulse frequency or progesterone positive feedback on gonadotropin release. This was a randomized, double-blind, placebo-controlled crossover study designed to test the hypothesis that acute, progesterone-related suppression of LH pulse frequency and progesterone-related augmentation of gonadotropin release are impaired in PCOS. Twelve normally cycling women and 12 women with PCOS completed study. Volunteers were pretreated with transdermal estradiol (0.2 mg/day) for 3 days and then underwent a frequent blood sampling study (20:00-20:00 h), during which they received micronized progesterone (100 mg) or placebo at 06:00 h. In a second study admission, volunteers received the intervention they did not receive during the first admission, but the protocol was otherwise identical. The primary outcome measures were LH secretory characteristics and circulating gonadotropin concentrations. Exogenous progesterone did not reduce LH pulse frequency in either group. Mean LH, pulsatile LH secretion, LH pulse mass, and mean FSH increased more with progesterone compared to placebo in both groups. Although trends toward less pronounced changes in LH pulse mass and pulsatile LH secretion were observed in the PCOS group, these differences were not statistically significant. In summary, exogenous progesterone did not suppress LH pulse frequency within 12 hours in estradiol-pretreated women, and the positive feedback effect of progesterone on gonadotropin release was not demonstrably impaired in PCOS. NEW & NOTEWORTHY: This study indicated that exogenous progesterone does not reduce LH pulse frequency within 12 h in women with PCOS, but progesterone acutely increased gonadotropin in these women. This study suggested that progesterone-related augmentation of gonadotropin release may be impaired in PCOS compared to normally cycling women, but this finding was not statistically significant. (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Kim, W. B., et al. (2022). "Robot-Assisted Laparoscopic Paravaginal Repair and Sacrocolpopexy in Patients With Pelvic Organ Prolapse." Urology 164: 151-156.
	Objective: To evaluate the surgical effects of robotic paravaginal repair and sacrocolpopexy in patients diagnosed with lateral cystocele due to paravaginal defect. Patients and Methods: Robotic paravaginal repair and sacrocolpopexy were performed contemporaneously in 43 patients with high-grade pelvic organ prolapse combined with a lateral or mixed cystocele. To objectively evaluate prolapse correction, the Pelvic Organ Prolapse Quantification (POP-Q) test was performed at the 12-month visit and the results compared to those of the preoperative period. Subjective satisfaction was scored using the Patient Global Impression of Improvement (PGI-I) questionnaire. Result(s): POP-Q measurement results before and after surgery, an objective indicator of surgery, the Ba and C scores improved significantly from 2.1 +/- 1.2 preoperatively to -2.0 +/- 1.1 postoperatively (P <.01), and from 0.3 +/- 1.3 preoperatively to -4.3 +/- 1.1 postoperatively (P <.01), respectively. In PGI-I questionnaire, the numbers of patients who awarded scores of 1 and 2 (evidencing high-level symptom improvement) were 33 at 1 month (76.7%), 30 at 3 months (69.8%), and 28 (65.1%) at 12 months. When respondents awarding 3 points (a little improvement) were included, the numbers rose to 38 (88.4%) at 1 and 3 months and 35 (81.4%) at 12 months, indicating satisfaction with symptom improvement. There were no critical complications during and after surgery, but complications such as de novo stress urinary incontinence that lower patient satisfaction occurred in some cases. Conclusion(s): Robot-assisted paravaginal repair and sacrocolpopexy can be safely performed in patients with cystocele-predominant pelvic organ prolapse and good surgical results can be expected with excellent effects.Copyright © 2021 Elsevier Inc.

Kim Yeon, J., et al. (2020). "Impact of intracavitary brachytherapy technique (2D versus 3D) on outcomes of cervical cancer: a systematic review and meta-analysis." Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 196(11): 973-982.
	Purpose: To perform a systematic review and meta-analysis of the impact of brachytherapy (BT) technique (two-dimensional [2D] or three-dimensional image-guided [3D]) on outcomes of cervical cancer patients.; Methods: PubMed and EMBASE databases were searched up to April 16, 2019, for studies which evaluated the effect of 3D-BT compared to 2D-BT in cervical cancer. Endpoints included cumulative incidence of severe toxicity, locoregional recurrence-free survival (LRRFS), progression-free survival (PFS), and overall survival (OS). Hazard ratios (HRs) were pooled in the meta-analysis using the random-effects model.; Results: Six studies of eight cohorts were included in the quantitative synthesis. The pooled HR regarding toxicity was evaluated in five cohorts in three studies, and the HR of 3D-BT compared to 2D-BT was 0.54 (95% confidence interval [CI] 0.37-0.77). All six studies were included for the synthesis for LRRFS, and the pooled HR favors 3D-BT (0.61 [95% CI 0.40-0.93]). For PFS, three studies were included for analysis and 3D-BT was superior to 2D-BT (HR = 0.75 [95% CI 0.59-0.96]). Five studies were included for the pooled HR regarding OS, and pooled HR of 3D-BT compared to 2D-BT was 0.65 (95% CI 0.40-1.06).; Conclusion: 3D-BT might reduce severe toxicity and improve LRRFS and PFS in patients with cervical cancer. 3D-BT should be considered for standard management of cervical cancer, and efforts for adopting this procedure in Korea should be pursued.

Kim, Y. J., et al. (2021). "Prevention of radiotherapy induced enteropathy by probiotics (PREP): protocol for a double-blind randomized placebo-controlled trial." BMC Cancer 21(1): 1032.
	BACKGROUND: Radiation induced enteropathy is a common complication of radiotherapy for pelvic tumors and adversely affects patient quality of life. Probiotics are thought to restore bowel microflora to optimal levels and reinforce intestinal barrier capacity. Although probiotics are effective in the treatment of radiation induced enteropathy, less is known about their efficacy to prevent radiation induced enteropathy. METHODS: This double-blind randomized placebo-controlled study will investigate the efficacy of probiotics to prevent radiation-induced enteropathy in patients with gynecologic or urologic cancer who received pelvic radiotherapy. The study is designed to enroll 248 eligible patients, who will be randomized 1:1 to a probiotic or placebo group. Toxicities will be evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DISCUSSION: The primary aim of this study is to provide high level evidence for the ability of probiotics to prevent acute radiation induced enteropathy. The secondary aims are to determine the effects of probiotics on the incidence of chronic radiation induced enteropathy and the safety of probiotics in patients with gynecologic or urologic cancer. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03978949 , Registered on 7 June 2019).

Kim, Y.-N., et al. (2023). "Randomized, two-arm, noncomparative phase 2 study of olaparib plus cediranib or durvalumab in HRR-mutated, platinum-resistant ovarian cancer: A substudy of KGOG 3045." International journal of cancer 153(12): 2032-2044.
	Choosing an optimal concomitant drug for combination with poly-ADP ribose polymerase (PARP) inhibitor based on patient-specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor-based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub-study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib-based combinations and biomarkers of patients with platinum-resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had BRCA mutations, which were similarly distributed between arms. Grade 3 or 4 treatment-related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD-L1 expression [CPS ≥10], CD8, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era. (© 2023 UICC.)

Kim Yong, B. (2022). "Salvage Systemic Therapy With or Without Stereotactic Ablative Radiotherapy for Recurrent Ovarian Cancer." ClinicalTrials.gov.
	Treatment Plan Arm 2; SABR Number of Fractions Preferred Doses Acceptable Doses 1 20 Gy 16‐24 Gy 3 30 Gy 24‐33 Gy 5 35 Gy 25‐40 Gy 10 40 Gy 35‐45 Gy Patient Evaluation: ‐ Interviews ‐ It was performed 3, 6, 9, 12, 18, 24, 30, and 36 months after the end of treatment. ‐ Medical history listening, physical examination and assessment of all possible side effects ‐ The relevant examination can be prescribed if necessary. ‐ Imaging examination ‐ one of CT or PET‐CT including areas suspected of recurrence or treatment is possible. ‐ If PET‐CT was not performed within two months before treatment, it is recommended to perform PET‐CT before treatment NOTE: Before treatment, it is recommended to perform the same examination as the imaging test that evaluated the treatment site. ‐ Tumor marker CA125 examination: performed on every visit after radiation therapy. ‐ Survey EORTC‐QLQ‐C30 questionnaire; prior to radiation therapy, 12, 24, and 36 months after treatment FACIT‐TS‐G (Arm 2 subjects); before radiation therapy, 12, 24, and 36 months after treatment.

Kim-Carolin, M. and T. Jure (2021). "Systematic review: mesh removal due to chronic pelvic pain after vaginal mesh surgery for stress urinary incontinence and pelvic organ prolapse."
	
Kim-Fine, S., et al. (2021). "Relationship of postoperative vaginal anatomy and sexual function: a systematic review with meta-analysis." International Urogynecology Journal 32(8): 2125-2134.
	Introduction and Hypothesis: This was a planned secondary analysis of a systematic review that described sexual function outcomes following pelvic organ prolapse (POP) surgery. We aimed to describe the relationship of pre- and postoperative vaginal anatomic measures with sexual function outcomes. Data Sources included the Medline, Embase, and clinicaltrials.gov databases from inception to April 2018.; Methods: The original systematic review included prospective, comparative studies that reported sexual function outcomes before and following POP surgery. Studies were extracted for population characteristics, sexual function outcomes, and vaginal anatomy, including total vaginal length (TVL) and genital hiatus. By meta-regression, we analyzed associations across studies between vaginal anatomic measurements and sexual function using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire-12 (PISQ-12) and dyspareunia outcomes.; Results: We screened 3124 abstracts and identified 74 papers representing 67 original studies. Among these, 14 studies reported TVL and PISQ-12 outcomes. Nine studies reported TVL and dyspareunia outcomes, eight studies reported GH and PISQ-12 outcomes, and seven studies reported GH and dyspareunia outcomes. We found no associations between anatomic measures and PISQ-12 or dyspareunia, although, we found a statistically significant association found between preoperative TVL and change in PISQ-12.; Conclusion: Across studies, the evidence does not support an association between vaginal anatomy and either validated, condition-specific sexual function questionnaires or dyspareunia. However, no study has directly analyzed these associations in the setting of pelvic floor reconstructive surgery. (© 2021. The International Urogynecological Association.)

Kingston, D. and R. Rocha (2020). "Telehealth and women's perinatal mental health." Women's mental health: A clinical and evidence-based guide.: 335-347.
	The use of e-technology as a platform for mental healthcare offers a potential solution for tackling the considerable challenges of providing acceptable, accessible, sustainable and timely mental healthcare. Research suggests that e-screening is acceptable to pregnant women and is valued for its anonymity and privacy, and emerging evidence suggests that e-screening tools have similar psychometric properties and ability to detect depression as traditional paper-based screening tools, while enhancing disclosure of sensitive topics. E-therapy as an alternative to face-to-face therapy meets pregnant women's strong preference for self-management. Emerging trial evidence suggests that web-based cognitive behaviour therapy with weekly telephone-based or email follow-up reduces symptoms of postpartum depression significantly. Evidence accumulated over the past decade and summarized in meta-analyses and systematic reviews in the general population supports this finding and indicate that e-therapy is useful for a wide variety of mental health disorders; is more effective when paired with email, text or telephone-based support; produces moderate to large reductions in symptoms; and has similar effectiveness and adherence to face-to-face psychotherapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Kinser, P., et al. (2021). "Study protocol for a multisite randomized controlled trial of an internet and mobile-based intervention for preventing and reducing perinatal depressive symptoms." Research in Nursing & Health 44(1): 13-23.
	Nearly 20% of women in the United States experience clinically significant depressive symptoms during pregnancy or the postpartum period. These women may benefit from easily accessible, nonpharmacologic, and inexpensive self-management approaches, such as via internet and mobile-based interventions, to prevent development of symptoms and/or intervene with current symptoms. This paper summarizes the research protocol of a nationally-funded large-scale randomized controlled study to evaluate "Mamma Mia," a self-guided program with 44 modules that women use throughout pregnancy to 6 months postpartum. The program contains a novel combination of components designed to enable women to enhance self-efficacy, emotional self-regulation, and perceived social support. The overall goal of this three-arm longitudinal randomized controlled trial is to evaluate the effects and mechanisms of this self-management approach in diverse women in the U.S. (n=1950). Enrolled pregnant women will be randomly assigned to one of three groups: (1) "Mamma Mia" alone, which is self-guided; (2) "Mamma Mia Plus" in which participants engage in the "Mamma Mia" modules plus receive brief guided support from a registered nurse; or (3) usual prenatal/postpartum care. The first specific aim is to evaluate effects by group on the primary outcome of interest, depressive symptoms, over time. The second aim is to evaluate effects by group on subjective well-being, anxiety, and stress. Using a conceptual framework based upon Individual and Family Self-Management Theory, the third aim is to evaluate possible mediators (self-efficacy, emotion self-regulation, perceived support) and possible moderators (e.g., race/ethnicity, type of healthcare clinician) of this self-management approach.Copyright © 2020 Wiley Periodicals LLC.

Kirakosyan, E. V., et al. (2022). "THE SIGNIFICANCE OF THE OOCYTE FACTOR IN THE DEVELOPMENT OF INFERTILITY OF UNCLEAR GENESIS." Akusherstvo i Ginekologiya (Russian Federation) 2022(1): 14-21.
	Infertility of unclear genesis is diagnosed in a married couple with no obvious defects in the reproductive system. A number of cases with infertility of unclear genesis are found to have impaired processes of fertilization and early embryogenesis through in vitro fertilization (IVF) programs. This may suggest that infertility of unclear genesis may be due, inter alia, to gamete defects. T he sources of world literature have been reviewed in the databases Scopus, Web of Science, MedLine, Cochrane CENTRAL, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), EMBASE, Global Health, CyberLeninka, and Russian Science Citation Index (RSCI) for a comprehensive study of the contribution of the oocyte factor to infertility. Diminished oocyte quality in most women is associated with their natural aging. However, some young women have low rates of fertilization and embryo development during IVF, which indirectly indicates the irregularly low quality of their oocytes and may be a manifestation of accelerated aging processes. In another portion of women, the low quality of oocytes is probably due to mutations in the genes encoding proteins involved in the processes of oocyte development. The low quality of oocytes may be associated with mutations in the PATL2, TUBB8, WEE2, and PAD16 genes, the change in expression of which leads to impaired oocyte maturation at metaphase of meiosis II (MII), to decreased oocyte ability for full fertilization and embryo formation, and to early embryonic development arrest, respectively. It is difficult to develop screening tests to identify these mutations, as they often occur sporadically and are not inherited due to infertility. Conclusion(s): Genetic diagnosis is necessary to optimize treatment policy for patients with infertility, including that of unclear genesis, and to reduce the time before making a decision, for example, on the use of donor oocytes.Copyright © A group of authors, 2022.

Kirca, N. and D. Adibelli (2021). "Effects of mother-infant skin-to-skin contact on postpartum depression: A systematic review." Perspectives in Psychiatric Care 57(4): 2014-2023.
	Purpose: The aim of this systematic review was to evaluate the effects of the skin-to-skin contact (SSC) method on postpartum depression.; Design and Methods: A systematic review of the literature was performed.; Findings: This review was completed with three studies meeting the research criteria. Two studies were randomized controlled studies and one study had a quasi-experimental design.; Practice Implications: SSC is such a low-cost intervention that it would be accessible, simple, and feasible for most mothers in the first postpartum weeks. By reducing mothers' depressive symptoms and physiological stress, SSC facilitates mothers' wellbeing and ultimately affects infants' development by enhancing the mother/infant relationship. (© 2021 Wiley Periodicals LLC.)

Kirca, N. and Ş. Özcan (2023). "The effects of nursing care based on Levine's Conservation Model on fatigue, depression, perceived social support, and sleep quality in infertile women: A randomized controlled trial." International journal of nursing knowledge 34(4): 284-296.
	Purpose: The purpose of this study was to investigate the effects of nursing care based on the Levine's Conservation Model on depression caused by infertility, fatigue, perceived social support, and sleep quality levels.; Methods: This study includes randomized controlled trial that was conducted from July 2019 to April 2020, with 65 Turkish women with infertility (experimental group: 34, control group: 31). We collected data using the Visual Similarity Scale for Fatigue, the Pittsburgh Sleep Quality Index, the Beck's Depression Inventory, and the Multidimensional Perceived Social Support Scale. The experimental group received nursing care based on the Levine's Conservation Model. Data were analyzed using t-tests and χ 2 tests analyses.; Findings: As a result of the measurements made, it was found that the experimental group had a lower fatigue level than the control group, with a statistically significant difference between the groups (p < 0.001). It was also found that the experimental group had higher energy and perceived social support scores than the control group after the practice, with a statistically significant difference between the groups (p < 0.001). As a result of the measurements made after the practice, it was found that the experimental group had a lower depression level than the control group, with a statistically significant difference between the groups (p < 0.001).; Conclusions: Nursing care based on the Levine's Conservation Model decreased fatigue and depression in women receiving infertility treatment and increased perceived social support and sleep.; Implications for Nursing Practice: This research provides important findings about nursing care based on Levine's Conservation Model for women receiving infertility treatment. It decreased depression and fatigue and increased perceived social support and sleep quality. (© 2022 NANDA International, Inc.)

Kırıcı, P. and E. S. Tanrıverdi (2021). "Effects of Different Progesterone Doses on the Concentrations of Proinflammatory and Anti-inflammatory Cytokines in Pregnant Women With Threatened Abortion." Cureus 13(11): e19333.
	Background and objective This study aimed to investigate how different doses of progesterone influence the concentrations of interleukin-6 (IL-6) and tumor necrotizing factor-alpha (TNF-α), which are proinflammatory cytokines, as well as that of IL-10, which is an anti-inflammatory cytokine, in pregnant women with threatened abortion. Materials and methods This is a prospective, single-center, randomized controlled trial conducted with 221 patients with a threatened abortion diagnosis. Group 1 consisted of IL-6, IL-10, and TNF-α values in pre-treatment blood samples from 221 patients diagnosed with imminent abortion. Group 2 included 81 patients who received natural oral 100 mg micronized progesterone MP twice a day for two weeks. Group 3 included 83 patients who were administered oral 200 mg of natural micronized progesterone MP twice a day for two weeks. Group 4 included 57 patients who received oral 200 mg of natural micronized progesterone MP twice a day for two weeks, and one depot progesterone was added to the treatment by administering it at a dosage of 500 mg/day intramuscularly. Results IL-6 values between groups were lower in group 4 compared to group 3 (p=0.007). When IL-10 values were compared between the groups, the IL-10 ratio was highest in group 4 and lowest in group 2 (p<0.001, p=0.003, p<0.001). When the TNF-α values between the groups were compared, the value in group 4 was decreased compared to groups 1 and 2 (p=0.031, p<0.001). In the logistic regression analysis, the IL-6 value above 12.01 increased the abortion imminens rate 1.01 times, and a TNF-α value above 11.04 increased the abortion imminens rate 1.21 times. Conclusion Progesterone used to treat imminent abortion reduces the levels of proinflammatory cytokines, such as IL-6 and TNF-α, while increasing those of anti-inflammatory cytokine IL-10 in proportion to the dose administered. Progesterone can prevent imminent abortion by generating an anti-inflammatory environment.

Kitada, F., et al. (2023). "[Safety and Efficacy of Robot-Assisted Surgery for Early Uterine Cancer in Our Institution over Five Years Since Its Introduction]." Gan to kagaku ryoho. Cancer & chemotherapy 50(3): 381-383.
	Lacking experience of laparoscopic surgery against gynecologic malignancies, we started performing robot-assisted surgery for uterine cancer in September 2017. Here we compared the safety and efficacy of robot-assisted surgery with those of open surgery in early-stage uterine cancer patients. The surgical time was significantly longer and the blood loss and hospital stay were significantly shorter for robot-assisted versus open surgery. No recurrence was observed after robot-assisted surgery. Robot-assisted surgery can be safely performed even in general hospitals and is an effective treatment option for early-stage uterine cancer patients.

Kite, C., et al. (2019). "Exercise, or exercise and diet for the management of polycystic ovary syndrome: a systematic review and meta-analysis." Systematic Reviews 8(1): 51.
	Background: Typically, management of PCOS focuses on lifestyle changes (exercise and diet), aiming to alleviate symptoms, and lower the associated risk of type 2 diabetes and cardiovascular disease. Our objective was to analyse evidence on the effectiveness of exercise in the management of PCOS, when compared to (i) usual care, (ii) diet alone, and (iii) exercise combined with diet, and also exercise combined with diet, compared to (i) control or usual care and (ii) diet alone.; Methods: Relevant databases were searched (June 2017) with no time limit for trial inclusion. Eligible trials employed a randomised or quasi-randomised design to measure the chronic effects of exercise, or exercise and diet in women with PCOS.; Results: Searches returned 2390 articles; of those, 27 papers from 18 trials were included. Results are presented as mean difference (MD) and 95% confidence intervals (95% CI). Compared with control, exercise had a statistical effect on change from baseline fasting insulin (MD - 2.44 μIU/mL, 95% CIs - 4.24 to - 0.64; very low-quality evidence), HOMA-IR (- 0.57, - 0.99 to - 0.14; very low-quality evidence), total cholesterol (- 5.88 mg/dL, - 9.92 to - 1.83; low-quality evidence), LDL cholesterol (- 7.39 mg/dL, - 9.83 to - 4.95; low-quality evidence), and triglycerides (- 4.78 mg/dL, - 7.52 to - 2.05; low-quality evidence). Exercise also improved VO 2 max (3.84 ml/kg/min, 2.87 to 4.81), waist circumference (- 2.62 cm, - 4.13 to - 1.11), and body fat percentage (- 1.39%, - 2.61 to - 0.18) when compared with usual care. No effect was found for change value systolic/diastolic blood pressure, fasting glucose, HDL cholesterol (all low-quality evidence), or waist-to-hip ratio. Many favourable change score findings were supported by post-intervention value analyses: fasting insulin (- 2.11 μIU/mL, - 3.49 to - 0.73), total cholesterol (- 6.66 mg/dL, - 11.14 to - 2.17), LDL cholesterol (- 6.91 mg/dL, - 12.02 to - 1.80), and VO 2 max (5.01 ml/kg/min, 3.48 to 6.54). Statistically lower BMI (- 1.02 kg/m 2 , - 1.81 to - 0.23) and resting heart rate (- 3.26 beats/min - 4.93 to - 1.59) were also revealed in post-intervention analysis. Subgroup analyses revealed the greatest improvements in overweight/obese participants, and more outcomes improved when interventions were supervised, aerobic in nature, or of a shorter duration. Based on limited data, we found no differences for any outcome between the effects of exercise and diet combined, and diet alone. It was not possible to compare exercise vs diet or exercise and diet combined vs diet.; Conclusion: Statistically beneficial effects of exercise were found for a range of metabolic, anthropometric, and cardiorespiratory fitness-related outcomes. However, caution should be adopted when interpreting these findings since many outcomes present modest effects and wide CIs, and statistical effects in many analyses are sensitive to the addition/removal of individual trials. Future work should focus on rigorously designed, well-reported trials that make comparisons involving both exercise and diet.; Systematic Review Registration: This systematic review was prospectively registered on the Prospero International Prospective Register of Systematic Reviews ( CRD42017062576 ).

Kiyak, H., et al. (2021). "Abdominal Hysterectomy with a Uterine Manipulator Minimizes Vaginal Shortening: a Randomized Controlled Trial." Journal of Investigative Surgery 34(10): 1052‐1058.
	BACKGROUND: We aimed to investigate the impact of adopting an uterine manipulator (UM) on the postoperative (VL) and female sexual function index (FSFI) in patients undergoing abdominal hysterectomy (AH) for benign gynecological disease. MATERIALS AND METHODS: Hysterectomies were performed with the Richardson technique; two variations, a UM or digital guidance, in this technique were used during the colpotomy step. Subjects were randomized and allocated to either hysterectomy with UM guidance (study group) or conventional hysterectomy (control group). Pre‐ and postoperative VL and FSFI were recorded for each patient. Additionally, surgeons' and residents' satisfaction in locating the colpotomy site was also scored by the surgical team postoperatively. RESULTS: There was a significant reduction in the VL (10.2 ± 1.2 cm vs. 8.3 ± 0.7 cm, p < 0.001) and FSFI score (21.0 ± 4.1 to 17.1 ± 3.6, p < 0.001) between the pre‐operation stage and three months post‐operation in the control group. However, no such significant changes were observed in the study group. Additionally, surgeons' and residents' satisfaction scores (SSS) for locating the colpotomy site were significantly higher in the study group as compared to the control group (p < 0.001). CONCLUSION: Our findings revealed that implementation of an UM in AH prevented unintended shortening of the postoperative VL and avoided a decline in the sexual function as compared to the standard AH procedure. These benefits were probably due to the precise determination of the colpotomy site that resulted from the use of UM in AH.

Klap, J., et al. (2021). "[Vaginal LASER therapy for genito-urinary disorders: A systematic review and statement from the Committee for Female Urology and Pelviperineology of the French Association of Urology]." Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie 31(11): 634-650.
	Introduction: Vaginal LASER therapy is increasingly used in the field of urogynecology, but several points remain unclear. Our goal was to produce a systematic review of available evidence and provide a critical appraisal of available data.; Methods: A systematic review until march 2020 was conducted using PubMed/MEDLINE, Cochrane and Embase databases. All studies about vaginal LASER use in the field of urogynecology were included.; Results: Forty studies have been included (8 for genitourinary syndrome of menopause, 19 for stress urinary incontinence, 3 for overactive bladder, 7 for urogenital prolapse, 3 for other indications). Data were heterogeneous, and level of evidence was weak or very weak. Few studies were comparative, and only 3 were randomized). Mild improvement of symptoms and quality of life and limited satisfaction were seen for genitourinary syndrome, stress urinary incontinence, overactive bladder and prolapse. Few adverse events were reported. However, major methodological biases were noted regarding efficacy and safety evaluation. No long-term results were available.; Conclusions: While Vaginal LASER therapy seem to provide encouraging results, the level of evidence supporting its use was weak, especially regarding long-term outcomes. Studies of better quality are warranted before any recommendation can be made. Current use should be limited to clinical research. (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Klapper-Goldstein, H., et al. (2022). "A systematic review of stem cell therapy treatment for women suffering from stress urinary incontinence." International Journal of Gynecology and Obstetrics 157(1): 19-30.
	Background: Stem cell therapy (SCT) is used for regeneration of injured tissues. This seems a novel promising strategy for restoring urethral sphincter function in patients with stress urinary incontinence (SUI). Objective(s): To summarize the clinical trials available to date on SCT for treatment of SUI in women. Search strategy: PubMed, Cochrane Library, Scopus and Embase. Selection Criteria: Prospective interventional case series, randomized prospective interventional study and prospective cohort study assessing women aged 18 years and over diagnosed with SUI and treated by SCT were included. The quality of studies was finally assessed using the JBI Critical Appraisal Checklists according to the PRISMA guidelines. Data Collection and Analysis: Nineteen studies (n = 773 patients) were selected for final analysis. These were conducted worldwide between the years 2005 and 2016. Although different cell types were used, general processing steps were similar. The follow-up period ranged between 6 weeks and 6 years and included common subjective and objective evaluation tools. Result(s): Overall, the studies imply that SCT for treatment of SUI is a safe and effective treatment. Conclusion(s): In our opinion, the initial results of SCT for the treatment of SUI seem promising. Standardization and validation of this treatment modality is required before it can be recommended for routine use.Copyright © 2021 International Federation of Gynecology and Obstetrics

Klebanoff Mark, A., et al. (2023). "Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis." Paediatric and perinatal epidemiology 37(3): 239-251.
	Background: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD.; Objectives: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery.; Data Sources: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis").; Study Selection and Data Extraction: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I 2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors.; Results: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I 2 = 62%, and 0.59 (95% CI 0.42, 0.82), I 2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I 2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I 2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history.; Conclusions: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation. (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Klein, J., et al. (2022). "The Role of Pessaries in the Treatment of Women with Stress Urinary Incontinence: A Systematic Review and Meta-Analysis." Female Pelvic Medicine and Reconstructive Surgery 28(6): E171-E178.
	Importance Pessaries are an important conservative therapy for stress urinary incontinence (SUI), but few studies have comprehensively evaluated their utility. Objective The objective of this study is to evaluate the existing evidence on the efficacy and safety of pessaries for the treatment of SUI. Study Design We searched for the terms "stress urinary incontinence"and "pessar/y/ies/ium"in PubMed, Embase, and Cinhal on June 10, 2020. Studies that characterized subjective and/or objective data were included. Studies performed in pediatric populations, pregnancy, and use of pessaries not for SUI were excluded. Two reviewers independently screened and assessed data quality and risk of bias according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Ten studies, including 376 patients, were included. In terms of subjective outcomes, 76% of 72 patients reported feeling continent after pessary treatment compared with 0% of 86 patients surveyed before pessary use (P < 0.0001). Both Urinary Distress Inventory and Incontinence Impact Questionnaire scores decreased significantly by 46.7% (n = 155 baseline, n = 139 follow-up; P < 0.0001) and 67.8% (n = 139 baseline, n = 107 follow-up; P < 0.0001), respectively. Significant objective measures associated with pessary use included increased urethral closure pressure (n = 122; g = 0.56; 95% confidence interval [CI], -0.66 to 1.77; P < 0.049) and decreased pad weight (n = 129 baseline; n = 118 follow-up; g = -0.89; 95% CI, -1.986 to 0.19; P = 0.009). Adverse events significantly decreased at greater than 6 months follow-up compared with less than 6 months follow-up, including pain (31.5%, n = 29/92 vs 14.3%, n = 5/35; P = 0.0513) and discomfort (50%, n = 46/92 vs 29.3%, n = 12/41; P = 0.0268). Conclusions Based on both subjective and objective measures, pessaries are an effective conservative treatment option for SUI. This supports pessary use, though larger studies with longer-term follow-up are warranted.Copyright © American Urogynecologic Society. All rights reserved.

Klein, O., et al. (2021). "Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: results of the CA209-538 clinical trial." Journal for Immunotherapy of Cancer 9(11).
	BACKGROUND: Patients with rare cancers represent 55% of all gynecological malignancies and have poor survival outcomes due to limited treatment options. Combination immunotherapy with the anti-programmed cell death protein 1 (anti-PD-1) antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab has demonstrated significant clinical efficacy across a range of common malignancies, justifying evaluation of this combination in rare gynecological cancers. METHODS: This multicenter phase II study enrolled 43 patients with advanced rare gynecological cancers. Patients received induction treatment with nivolumab and ipilimumab at a dose of 3 mg/kg and 1 mg/kg, respectively, every 3 weeks for four doses. Treatment was continued with nivolumab monotherapy at 3 mg/kg every 2 weeks until disease progression or a maximum of 2 years. The primary endpoint was the proportion of patients with disease control at week 12 (complete response, partial response or stable disease (SD) by Response Evaluation Criteria In Solid Tumor V.1.1). Exploratory evaluations correlated clinical outcomes with tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). RESULTS: The objective response rate in the radiologically evaluable population was 36% (12/33 patients) and in the intention-to-treat population was 28% (12/43 patients), with additional 7 patients obtaining SD leading to a disease control rate of 58% and 44%, respectively. Durable responses were seen across a range of tumor histologies. Thirty-one (72%) patients experienced an immune-related adverse event (irAE) with a grade 3/4 irAE observed in seven (16%) patients. Response rate was higher among those patients with baseline PD-L1 expression (≥1% on tumor cells) but was independent of TMB. CONCLUSIONS: Ipilimumab and nivolumab combination treatment has significant clinical activity with a favorable safety profile across a range of advanced rare gynecological malignancies and warrants further investigation in these tumor types.

Kleine, I. (2020). "Interventions to prevent perinatal depression: US Preventive Services Task Force Recommendation Statement." Archives of disease in childhood. Education and practice edition 105(4): 242-243.
	In 2019, the US Preventive Services Task Force (USPSTF) commissioned a systematic evidence review to assess the benefits, risks, target population and timing of preventive interventions for postnatal depression (PND).1 Given the high incidence of PND—15–20% of women being affected by depression and anxiety in the first year after childbirth in the UK2—and significant short-term and long-term consequences for mother and child,1 3 4 awareness among paediatricians of effective risk-stratifying and preventive strategies is of significant importance to maternal, child and public health. What should I be doing? Be aware of the strong association between maternal mental … View Full Text

Kling Juliana, M., et al. (2023). "Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy." Maturitas 167: 113-122.
	Objectives: To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group.; Methods: Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 μg/day transdermal 17β (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17β-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty.; Results: All women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17β-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time.; Summary: In healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation.; Gov Numbers: NCT00154180, NCT00623311.; Competing Interests: Kejal Kantarci serves on the data safety monitoring board for Takeda Global Research and Development Center, Inc.; receives research support from Avid Radiopharmaceuticals, Eli Lilly, the NIH, and the Alzheimer's Drug Discovery Foundation. Juliana M. Kling has been a prior consultant to Proctor & Gamble and Triangle Insights Group. Lubna Pal is on advisory board for Ferring and serves as a consultant to Flo Health. Other authors have no competing interests to disclose. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Klopp, A., et al. (2022). "RANDOMIZED TRIAL OF PELVIC RADIATION WITH AND WITHOUT CONCURRENT CISPLATIN IN PATIENTS WITH A PELVIC ONLY RECURRENCE OF ENDOMETRIAL CANCER." International Journal of Gynecological Cancer 32(Supplement 3): A5.
	Objectives The pelvis is a common site of recurrence for patients with endometrial cancers. A randomized trial was conducted to compare progression-free survival in patients treated with radiation therapy alone as compared to radiation therapy with concurrent cisplatin-based chemotherapy. Methods 165 Patients were accrued between February 2009 and August 2020. Women with recurrent endometrial carcinoma limited to the pelvis were eligible. The median time for follow up for vital status was 60 months. Results Most patients had grade 1 or 2 endometroid endometrial cancer (81%) and most recurrences were vaginal (86%). Radiation therapy was delivered to the pelvis with 3D or IMRT techniques followed by HDR or LDR interstitial or intracavitary brachytherapy. Chemotherapy was delivered with weekly cisplatin. Grade 4 or higher acute adverse event were reported in 8 participants in the chemotherapy and radiation arm as compared to 1 treated with radiation only. 68% of patients treated with radiation therapy were alive and progression- free as compared to 59.8% of those that received chemotherapy and radiation. Overall, patients treated with weekly cisplatin had a lower rate of PFS as compared to patients treated with radiation alone (stratified HR=1.40, 95% CI: 0.82-2.39, p=0.8919). Conclusions Results of this randomized trial suggest that the addition of chemotherapy does not improve, and may worsen, outcomes for patients treated with definitive radiation therapy for recurrent endometrial cancer. Those with low grade and vaginal apex recurrences may be best treated with radiation therapy alone.

Kluivers Kirsten, B., et al. (2023). "Subjective outcomes 12 years after transvaginal mesh versus native tissue repair in women with recurrent pelvic organ prolapse; a randomized controlled trial." International Urogynecology Journal 34(7): 1645-1651.
	Introduction and Hypothesis: The present study describes an extended follow-up study after 12 years and focusses on subjective outcomes of women who underwent surgery for recurrent pelvic organ prolapse in the randomized index study.; Methods: One hundred and ninety-four (194) women had been randomized in the original study and in the present study, 45 (47%) in the vaginal mesh repair versus 43 (43%) women with conventional vaginal native tissue repair completed the long-term questionnaires. The mesh used was a first-generation non-absorbable mesh kit. All types of conventional vaginal native tissue repairs were allowed, and additional vaginal native tissue repairs were allowed in the mesh group. The questionnaires as applied at baseline were used. The Patient Global Impression of Improvement questionnaire (PGI-I) was the primary outcome.; Results: At 12 years, 30 (71%) women in the mesh group versus 23 (59%) women in the native tissue repair group reported to be PGI-I (very) much improved (p=0.24). There were no differences found in any of the questionnaire domains. There was, however, a higher number of women who had had additional operations for recurrent pelvic organ prolapse, stress urinary incontinence, and/or exposure in the mesh group: 18 women (40%) in the mesh group versus 8 women (19%) in the native tissue repair group (p=0.03).; Conclusions: There was no difference in subjective outcome between the groups, but there was a statistically significant higher number of women who had needed further operations. This study confirms that vaginal mesh should not be used in all women with recurrent pelvic organ prolapse. (© 2023. The Author(s).)

Knauss, T., et al. (2023). "The cost-effectiveness of opt-in and send-to-all HPV self-sampling among long-term non-attenders to cervical cancer screening in Norway: The Equalscreen randomized controlled trial." Gynecologic Oncology 168: 39-47.
	OBJECTIVE: We assessed the cost-effectiveness of mailing a human papillomavirus self-sampling (HPV-ss) kit, directly or via invitation to order, compared with mailing reminder letters among long-term non-attenders in Norway. METHODS: We conducted a secondary analysis using the Equalscreen study data with 6000 women aged 35-69 years who had not screened in 10+ years. Participants were equally randomized into three arms: reminder letter (control); invitation to order HPV-ss kit (opt-in); directly mailed HPV-ss kit (send-to-all). Cost-effectiveness (2020 Great British Pounds (GBP)) was estimated using incremental cost-effectiveness ratios (ICERs) per additional screened woman, and per additional cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from extended and direct healthcare perspectives. RESULTS: Participation, CIN2+ detection, and total screening costs were highest in the send-to-all arm, followed by the opt-in and control arms. Non-histological physician appointments contributed to 67% of the total costs in the control arm and ≤ 31% in the self-sampling arms. From an expanded healthcare perspective, the ICERs were 135 GBP and 169 GBP per additional screened woman, and 2864 GBP and 4165 GBP per additional CIN2+ detected for the opt-in and send-to-all, respectively. CONCLUSIONS: Opt-in and send-to-all self-sampling were more effective and, depending on willingness-to-pay, may be considered cost-effective alternatives to improve screening attendance in Norway.

Knisely, A., et al. (2024). "Phase 1/2 trial of avelumab combined with utomilumab (4-1BB agonist), PF-04518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies." Cancer 130(3): 400-409.
	Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies. Method(s): The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the duration of response, progression-free survival, and overall survival. Result(s): Forty patients were included (35% with cervical cancer, 30% with endometrial cancer, and 35% with ovarian cancer). Most patients (n = 33; 83%) were enrolled in arms A-C (no radiation). Among 35 patients who were evaluable for efficacy, the ORR was 2.9%, and the DCR was 37.1%, with a median duration of stable disease of 5.4 months (interquartile range, 4.1-7.3 months). Patients with cervical cancer in arm A (avelumab and utomilumab; n = 9 evaluable patients) achieved an ORR of 11% and a DCR of 78%. The median progression-free survival was 2.1 months (95% CI, 1.8-3.5 months), and overall survival was 9.4 months (95% CI, 5.6-11.9 months). No dose-limiting toxicities or grade 3-5 immune-related adverse events were observed. Conclusion(s): The findings from this trial highlight that, in heavily pretreated patients with gynecologic cancer, even multidrug regimens targeting multiple immunologic pathways, although safe, did not produce significant responses. A DCR of 78% in patients with cervical cancer who received avelumab and utomilumab indicates that further research on this combination in select patients may be warranted.Copyright © 2023 American Cancer Society.

Knisely, A., et al. (2021). "The Role of Minimally Invasive Surgery in the Care of Women with Ovarian Cancer: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(3): 537-543.
	Objective: To synthesize evidence from studies investigating survival outcomes for patients with ovarian cancer undergoing minimally invasive surgery (traditional or robotic laparoscopy) compared with those for patients with ovarian cancer undergoing laparotomy.; Data Sources: We searched Ovid MEDLINE and Embase (from inception to December 2019).; Methods of Study Selection: Observational cohort studies and randomized controlled trials that compared risk of recurrence or death between women undergoing minimally invasive and open procedures for staging (10), interval cytoreduction (4), secondary cytoreduction (2), and evaluation of resectability (1) were included.; Tabulation, Integration, and Results: Data on the number of participants, number of deaths and recurrences, and results of analyses of overall or progression-free survival were abstracted for all studies. A random-effects meta-analysis was used to pool the results of studies comparing minimally invasive staging and open staging. The surgical approach (minimally invasive versus open) was not significantly associated with hazard of death or recurrence (pooled hazard ratio 0.92; 95% confidence interval, 0.61-1.38) or all-cause mortality (pooled hazard ratio 0.96; 95% confidence interval, 0.49-1.89). One randomized trial demonstrated that diagnostic laparoscopy could triage patients to neoadjuvant chemotherapy and avoid suboptimal primary surgery, without affecting recurrence-free or overall survival. Most studies included in this review were observational and at high risk for bias, and few studies accounted for potential confounding.; Conclusion: Although existing studies do not demonstrate deleterious survival effects associated with minimally invasive surgery for ovarian cancer, these data must be viewed with caution given the significant methodologic shortcomings in the existing literature. (Copyright © 2020. Published by Elsevier Inc.)

Kobayashi, E., et al. (2023). "Overview of laparoscopic surgery for cervical cancer in Japan: Updates after the laparoscopic approach to cervical cancer trial." The Journal of Obstetrics and Gynaecology Research 49(1): 90-102.
	Laparoscopic radical hysterectomy (LRH) for cervical cancer has been reported to be similar oncologic outcome compared to abdominal radical hysterectomy (ARH) in many retrospective studies. In Japan, LRH has been covered by insurance since April 2018. In 2018, the same year that LRH became covered by insurance, Ramirez et al. at MD Anderson Cancer Center reported the results of a large phase III laparoscopic approach to cervical cancer trial (LACC trial) on the prognosis of open versus laparoscopic/robot-assisted minimally invasive radical hysterectomy. The results showed that minimally invasive approaches were associated with a higher rate of recurrence and death. At this point, it is not clear what is wrong with LRH and why it has a poorer prognosis compared to ARH. In this report, after the LACC report, we would like to review the current status of minimally invasive surgery for cervical cancer and future directions. (© 2022 Japan Society of Obstetrics and Gynecology.)

Kobayashi, H. (2022). "Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review." Heliyon 8(11): e11487.
	Epithelial ovarian cancer (EOC) is a gynecologic malignancy with a poor prognosis due to resistance to first-line chemotherapeutic agents. Some cancer cells are primarily dependent on glycolysis, but others favor mitochondrial oxidative phosphorylation (OXPHOS) over glycolysis. Changes in metabolic reprogramming have been reported to be involved in cancer cell survival. In this review, we summarize the metabolic profiles (e.g., metabolic heterogeneity, plasticity, and reprogramming) and adaptation to the dynamic tumor microenvironment and discuss potential novel therapeutic strategies. A literature search was performed between January 2000 and March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. Ovarian cancer cells, including cancer stem cells, depend on glycolysis, OXPHOS, or both for survival. Several environmental stresses, such as nutrient starvation or glucose deprivation, hypoxic stress, acidification, and excessive reactive oxygen species (ROS) generation, reprogram the metabolic pathways to adapt. The interaction between tumors and adjacent stromal cells allows cancer cells to enhance mitochondrial energy metabolism. The metabolic reprogramming varies depending on genomic and epigenetic alterations of metabolism-related genes and the metabolic environment. Developing accurate and non-invasive methods for early identification of metabolic alterations could facilitate optimal cancer diagnosis and treatment. Cancer metabolism research has entered an exciting era where novel strategies targeting metabolic profiling will become more innovative.; Competing Interests: The authors declare no conflict of interest. (© 2022 The Author(s).)

Kobayashi, H. (2023). "Efficacy, Adverse Events, and Challenges of Dienogest in the Management of Symptomatic Adenomyosis: A Comparison with Different Hormonal Treatments." Gynecologic and Obstetric Investigation 88(2): 71-80.
	Background: Adenomyosis is an estrogen-dependent gynecologic condition that can cause pain symptoms, heavy menstrual bleeding, and infertility. Several treatments, including hormonal therapy, can improve patients' quality of life through alleviating symptoms. Dienogest (DNG), a 19-norsteroid derivative oral progestin, is a promising treatment option for adenomyosis.; Objectives: This review aims to summarize the clinical outcomes (efficacy and adverse events) of DNG treatment for symptomatic adenomyosis compared with other hormonal treatments, discuss the mechanism underlying adverse events, and identify future challenges.; Methods: A literature search was performed across the PubMed and Google Scholar databases up to March 2022 to identify relevant literature.; Outcome: Out of 449 identified records, 37 articles met the inclusion and exclusion criteria. Five prospective and three retrospective studies showed that DNG and other hormonal agents had similar efficacy for pain relief; however, the most common adverse event of DNG was abnormal uterine bleeding. Specific demographic and clinicopathologic characteristics have been identified as associated with an increased risk of bleeding. Several factors, such as diffuse or type 1 adenomyosis, advanced reproductive age, severe dysmenorrhea, elevated serum CA125 levels, or low hemoglobin levels, may be implicated in bleeding risk; however, there is no accurate and reliable parameter. Future challenges with the widespread use of DNG include validation of candidate risk indicators and approaches to treat diffuse or type 1 adenomyosis.; Conclusions and Outlook: DNG represents an important therapeutic option to be included in the treatment algorithm for adenomyosis owing to sufficient pain relief, despite high rates of bleeding-related adverse events. Clinicians should consider an individual's potential risk factors for bleeding until high-quality evidence is available. (© 2023 S. Karger AG, Basel.)

Kobayashi, R., et al. (2022). "Effect of Hyaluronate Acid Injection on Dose-Volume Parameters in Brachytherapy for Cervical Cancer." Advances in Radiation Oncology 7(3): 100918.
	Purpose: Hyaluronate gel has been injected as a spacer into the rectovaginal fossa and vesicouterine fossa during brachytherapy for patients with cervical cancer at our institution. The effect of hyaluronate gel injection (HGI) on dose-volume parameters was investigated in this study.; Methods and Materials: Between July 2008 to January 2020, a total of 104 patients (non-HGI group: 52 patients; HGI group: 52 patients) who underwent curative radiation therapy for cervical cancer were selected. The total doses of external beam radiation therapy and brachytherapy for high-risk clinical target volume (CTV HR ) D 90 , bladder D 2cc , and rectal D 2cc were converted to the equivalent dose in 2 Gy fractions (EQD2) and were analyzed for association with HGI.; Results: Median CTV HR D 90 (EQD2) in the non-HGI group was 76.0 Gy (63.7-99.5 Gy), and in the HGI group it was 79.4 Gy (52.6-97.5 Gy) ( P = .017). The median bladder D 2cc and rectal D 2cc (EQD2) were 62.9 Gy and 56.0 Gy in the non-HGI group and 63.7 Gy and 54.8 Gy in the HGI group, which had no significant difference.; Conclusions: In cases with HGI, a significant CTV HR D 90 dose increase was obtained with sufficient bladder and rectal doses suppression. (© 2022 The Author(s).)

Kobus, S., et al. (2022). "Music Therapy in Preterm Infants Reduces Maternal Distress." International Journal of Environmental Research and Public Health 20(1).
	Preterm delivery is a stressful event for mothers, posing them at risk for post-traumatic stress reactions. This study examined the degree of depressive symptoms and post-traumatic stress in mothers of preterm infants born before 32 gestational weeks depending on whether the infant received music therapy in the neonatal intensive care unit (NICU) or not. We included 33 mothers of preterm infants enrolled in a previously described prospective randomized controlled trial, of whom 18 received music therapy (mean mothers' age 34.1 ± 4.6 years) and 15 did not (mean mothers' age 29.6 ± 4.2). The degree of depressive symptoms, anxiety and acute stress reactions of these mothers were measured by using the German version of the Center for Epidemiologic Studies Depression Scale (CES-D) and Impact of Events Scale-Revised (IES-R) one week after birth (T1) and at infants' hospital discharge (T2). 605 music therapy sessions with a mean duration of 24.2 ± 8.6 min (range 10 to 50 min) were conducted two times a week from the second week of life (T1) until discharge (T2) to the infants from the intervention group. The infants from the control group received standard medical care without music therapy. The mean total CES-D score decreased from T1 (mean 34.7, 95% Confidence Interval (CI) 31.1-38.1) until T2 in all mothers (mean 16.3, 95% CI 12.6-20.1). Mothers whose infants received music therapy showed stronger declines of depressive and stress symptoms (with music therapy: CES-D mean difference of total score 25.7, 95% CI 20.0-31.3, IES-R mean difference of total score 1.7, 95% CI 0.9-2.5, IES-R mean difference of subcategory hyperarousal 10.2, 95% CI 6.2-14.3; without music therapy: CES-D mean difference of total score 9.5, 95% CI 3.8-15.3, IES-R mean difference of total score 0.1, 95% CI -1.0-1.2, IES-R mean difference of subcategory hyperarousal 1.6, 95% CI -4.7-7.9). Effect sizes were strong for CES-D, IES-R, and the hyperarousal subcategory, moderate for intrusion, and low for avoidance. These findings show that mothers of preterm infants are highly susceptible to supportive non-medical interventions such as music therapy to reduce psychological symptoms and distress during their infants' NICU stay.

Koçak Derya, Y. and Y. Varişoğlu (2022). "The effect of music therapy on menopausal symptoms and depression: a randomized-controlled study." Menopause (New York, N.Y.) 29(5): 545-552.
	Objective: Menopausal syndrome generally includes psychological problems. Listening to music has been used to cope with changes during this period. This study was conducted to determine the effect of listening to music on the symptoms of menopause and depression levels.; Methods: This randomized-controlled study was carried out between July 2019 and December 2020. The study sample consisted of 48 postmenopausal women (21 in the music group and 27 in the control group). Music was played by the researcher to the postmenopausal women in the intervention group in a total of 18 sessions for six weeks. The data were collected using an introductory information form, Beck depression inventory (BDI), and menopause rating scale (MRS).; Results: The posttest MRS scores of the women in the control group were higher than those in the music group, without a statistically significant difference between the groups (P > 0.05). Comparison of the post-test BDI scores of the participants in the music and control groups revealed a significant decrease in the depression scores among the women in the music group (P = 0.036). Comparison of the pretest and posttest MRS and BDI differences between the participants showed a statistically significant decrease in the MRS total and sub-scale scores among the women in the music group after the intervention.; Conclusions: There was a significant decrease of posttest BDI scores of the women in the music group but not in the control group. Listening to music can help reduce depression levels and symptoms of menopause in postmenopausal women. Music could be used as a nonpharmacological therapeutic option in nursing care.; Competing Interests: Financial disclosures/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Koçak, V., et al. (2021). "The development of the postpartum mobile support application and the effect of the application on mothers' anxiety and depression symptoms." Archives of Psychiatric Nursing 35(5): 441-449.
	OBJECTIVE: The study aimed to develop the postpartum mobile support application to support postpartum mothers and to examine the effects of the use of mobile app on mothers' anxiety level and depression symptoms. RESEARCH DESIGN/SETTING: It is a parallel group pretest-posttest randomized controlled study carried out between July 2017 and February 2020. The mothers (62 in the experiment and 62 in the control group) who gave birth in full-term at a university hospital in Konya province in Turkey and who had healthy newborns constituted the study group. Data were collected using the Information Form, the STAI State and Continuity Anxiety Scale, and the Edinburgh Postpartum Depression Scale. Mixed pattern variance analysis (mixed anova), t test in dependent groups, t test and chi square analysis in independent groups were used to analyze the data. FINDINGS: Most of the mothers who used the application fed their baby only with breast milk and felt more sufficient about breastfeeding. The depression symptoms of mothers using the postpartum mobile support application was lower than that of the mothers in the control group; however, it was found that the application was not adequate alone to decrease anxiety levels and depression symptoms (p > 0.05). CONCLUSIONS: The postpartum mobile support application is an important and useful source in accessing reliable information; however, it was found to be insufficient to lower anxiety levels and prevent depression symptoms at the end of the six-week postpartum period.

Kocher, N. J., et al. (2021). "Patient-reported onset of symptom improvement following initial intradetrusor onabotulinumtoxina injections for overactive bladder." Journal of urology 206(SUPPL 3): e934.
	INTRODUCTION AND OBJECTIVE: Intradetrusor onabotulinumtoxinA (BTX-A) is a common third-line therapy for treatment of refractory overactive bladder (OAB), however several gaps exist in pre-and post-procedural standard of care. Prior studies have demonstrated BTX-A efficacy at 2-3 weeks, but there are limited data documenting when patients should begin to note symptom improvement. We performed a prospective study evaluating several factors involved in the BTX-A patient care pathway. The primary aim of this abstract was to determine patient-reported temporal improvement in symptoms following initial BTX-A therapy. METHOD(S): A prospective, non-randomized study of patients with non-neurogenic, refractory urgency-frequency syndrome and urgency urinary incontinence undergoing first-time BTX-A injection under local anesthesia was performed. Intradetrusor injection of 100 units BTX-A was performed by one of 3 FPMRS-trained providers using a standard 20-site template. Patients were required to discontinue their OAB medication(s) at the time of BTX-A injection for 3 weeks and complete a daily Patient Global Impression of Improvement (PGI-I) diary during this time. Data were collected at 1 month, including final satisfaction score and adverse outcomes. Descriptive analysis was performed in R programming. RESULT(S): 25 patients were included (24 female, 1 male). Median age was 75 years and BMI was 34.3. Figure 1 shows a jitter plot with loess smoothed fit of patient-reported PGI-I over time following BTX-A injection. 24 patients (96%) reported symptom improvement (PGI <4) by 3 weeks, with 19 patients (76%) documenting at least "much better" (PGI >2). Median time to first improvement (PGI <4) was 1 day, at least "much better" was 4 days, and median time to maximum patient improvement was 6 days. Median final satisfaction score was PGI 2 ("much better"). Adverse outcomes included UTI in 2 patients (8%) and incomplete emptying requiring transient intermittent catheterization in 1 patient (4%). CONCLUSION(S): Patients with refractory OAB undergoing firsttime 100 units BTX-A injection reported median time to first improvement (PGI <4) at 1 day, at least "much better" at 4 days, and median time to maximum patient improvement at 6 days. These data may help further counsel patient expectations following initial BTX-A therapy.

Kocjancic, E., et al. (2019). "Complications of urethral bulking therapy for female stress urinary incontinence." Neurourology and Urodynamics 38(S4): S12-S20.
	Aims: To review, report, and discuss the complications associated with urethral bulking therapy in female stress urinary incontinence. Method(s): An extensive nonsystematic literature review on complications associated with injectable bulking agents used in the clinical practice was conducted. We reviewed articles published in English and indexed in the PubMed, Embase, and Google Scholar databases. Original articles, case reports, and case series were taken into consideration. Data regarding the safety of injectable bulking agents and the complications associated with their utility within the context of urethral bulking therapy for female stress urinary incontinence were extracted and discussed. Result(s): Approximately, 1/3 of the patients experience some type of a complication after urethral bulking therapy. The majority of these complications are of low grade, transient, do not necessitate additional surgical intervention, and amenable to treatment with conservative measures such as clean intermittent catheterization and antibiotics. However, more serious complications such as abscess formation, delayed hypersensitivity reactions, and vaginal erosion have been reported. Some of the injectable bulking agents have been withdrawn from the market because of their unfavorable adverse effect profile. Conclusion(s): Urethral bulking therapy can be considered as a low-risk procedure. However, it is not without complications which can be severe in rare instances. The search for the ideal urethral bulking agent is ongoing and future comparative studies assessing the safety and efficacy of these compounds in randomized controlled settings are warranted.Copyright © 2018 Wiley Periodicals, Inc.

Koenig, I., et al. (2021). "Activation patterns of pelvic floor muscles in women with incontinence while running: a randomized controlled trial." International Urogynecology Journal 32(2): 335-343.
	INTRODUCTION AND HYPOTHESIS: Running is known to cause urinary leakage in women with stress urinary incontinence (SUI). Task-specific fiber-type recruitment while running can be estimated using wavelets. The aim of this study was to compare the effect of a new physiotherapy program including involuntary, reflexive training with a standard physiotherapy program on pelvic floor muscle (PFM) activation patterns and fiber-type recruitment behavior while running. METHODS: In this triple-blinded randomized controlled trial, women with SUI were randomly allocated to the control group (CON), which performed a standard physiotherapy program, or the experimental group (EXP), which received additional involuntary, reflexive training. PFM electromyography (EMG) was recorded during 10 s at three running speeds and analyzed using Morse wavelets. The relative distribution of power (%) over the frequencies from 20 to 200 Hz was extracted and analyzed within six-time intervals of 30 ms. Statistical nonparametric mapping was performed to identify power spectra differences. RESULTS: Thirty-nine (CON) and 38 (EXP) women were included. The power spectra showed no statistically significant group differences. The time intervals from 30 ms before to 30 ms after initial contact showed significantly lower intensities than the intervals from 30 to 150 ms after initial contact in the lowest and higher intensities in the highest frequencies for all running speeds and both groups. CONCLUSIONS: Power spectra shifts toward higher frequency bands in the pre-initial contact phase could indicate a feed-forward anticipation and a muscle tuning for the expected impact of initial contact event in order to maintain continence.

Kolahdooz, G., et al. (2023). "The effect of crocin versus sertraline in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial." International clinical psychopharmacology 38(1): 9-15.
	Postpartum depression (PPD) is one of the most common conditions among women. This study aimed to investigate the effect of crocin compared to sertraline in women with mild to moderate PPD. This trial study was performed on women with PPD. Patients in two groups received crocin (15 mg) and sertraline (50 mg) daily for 3 months, respectively. Patients have assessed by Beck's Depression Inventory-II (BDI-II) and Beck's Anxiety Inventory (BAI) at 0-12 weeks. A total of 64 patients were examined. The mean of the BDI-II score in the crocin group decreased after 3 months from 20.75 to 4.93 (P = 0.0001). In the sertraline group, the mean score of BDI-II decreased after 3 months from 21.06 to 2.37 (P = 0.0001). The mean of the BAI score in the crocin group decreased significantly after 3 months from 13.75 to 4.06 (P = 0.0001) and in the sertraline group from 12.9 to 2.71 (P = 0.0001). No significant difference was observed between crocin and sertraline after the clinical trial (P = 0.5). No severe side effects were observed during the study in the two groups. The results of this study showed that crocin (15 mg daily) could be useful in treating PPD. Furthermore, this study showed that crocin, with far fewer side effects than chemical drugs, can be widely used in PPD, but due to the small sample size further studies are necessary to confirm such efficiency. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Kolanska, K., et al. (2021). "Unexplained recurrent implantation failures: predictive factors of pregnancy and therapeutic management from a French multicentre study." Journal of Reproductive Immunology 145: 103313.
	Introduction: Recurrent implantation failure is defined as the absence of pregnancy after at least three transfers of good‐quality embryos after in vitro fecundation/intracytoplasic sperm injection. Aim: The aim of this study was to describe a multicentre cohort of women with unexplained RIF, to analyse the factors associated with clinical pregnancy and to evaluate the immunomodulatory therapies efficacy. Methods: Women were consecutively recruited from university departments with unexplained RIF. Results: Sixty‐four women were enrolled with mean age 36 ± 3 years. The rates of clinical pregnancy in 64 women were compared in untreated and treated cycles and according to therapies used during the last prospectively followed embryo transfer. A clinical pregnancy after the transfer was noted in 56 % pregnancies on intralipids and in 50 % on prednisone, versus 5 % in untreated ones (p < 0.001). The 340 embryo transfers of these 64 women resulted in 68 clinical pregnancies and 18 live births. Clinical pregnancies were significantly more frequent in treated versus untreated embryo transfers (44 % vs 9 %; p < 0.001) with odds ratio at 8.13 (95 % CI 4.49–14.72, p < 0.0001). Cumulative pregnancy rates were higher for steroid‐treated transfers than for untreated transfers when considering overall transfers before and after using steroids and also only those under steroids. Cumulative pregnancy rates were not different from steroid‐ and intralipid‐treated embryo transfers Conclusions: In this multicentre study of women with unexplained RIF, use of immunomodulatory treatments before embryo transfer resulted in higher clinical pregnancy. Randomised, well‐designed studies in well‐defined population of RIF women are necessary to confirm our preliminary data.

Kolesar Jill, M., et al. (2021). Phase 1 Dose Escalation of ArtemiCoffee.
	No Results Available Drug: Artemisia annua 450mg|Drug: Artemisia annua 900mg|Drug: Artemisia annua 1350mg|Drug: Artemisia annua 1800mg|Drug: Artemisia annua - recommended phase II dose Recommended Phase II Dose|Progression Free Survival Female Phase 1 18 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MCC-20-GYN-08 December 2024 This is a phase I dose-escalation study of Artemisia annua (Aa) in patients with advanced ovarian cancer who have completed front-line chemotherapy with carboplatin and paclitaxel. The primary objective of this study is to determine the recommended phase II dose (RP2D) of Artemisia annua.

Köln, U. and Z. K. S. Köln (2023). Chemo-radio-immunotherapy With Nivolumab and Ipilimumab Treatment in Locally Advanced Cervical Cancer Patients.
	No Results Available Drug: Pre-Chemo-radio-immunotherapy Treatment (Nivolumab/Ipilimumab)|Drug: Concurrent Chemo-radio-immunotherapy (Nivolumab/Ipilimumab)|Procedure: Maintenance Treatment (Nivolumab/Ipilimumab) Progression free survival (PFS)|The adverse events according to NCI-CTCAE v5.0 Female Phase 2 0 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Uni-Koeln-4513 July 2026

Kolodynska, G., et al. (2022). "Assessment of the Effectiveness of the Sonofeedback Method in the Treatment of Stress Urinary Incontinence in Women-Preliminary Report." Journal of Clinical Medicine 11(3): 659.
	Urinary incontinence is a common problem that affects postmenopausal women. This ailment has a negative impact on many aspects of life, significantly limiting everyday functioning related to professional work, physical activity or the intimate sphere. The aim of the study was to assess the effectiveness of the sonofeedback method in reducing the severity of urinary incontinence in postmenopausal women with a urinary incontinence problem. A total of 60 patients aged 45-65 with stress urinary incontinence, confirmed by a gynecologist, were qualified for the study. All persons qualified for the study were randomly assigned to study group A (n = 20), comparative B (n = 20) and control C (n = 20). Patients from group A were treated with sonofeedback of the pelvic floor muscles. In group B, the combined electrostimulation method was used with biofeedback training. Group C was a control group in which only the measured parameters were measured at the same time interval as those carried out in groups A and B. In all patients, three times: before the therapy, after the fifth procedure and after the end of the therapy, the incidence and severity of stress urinary incontinence were assessed-Gaudenz questionnaire and the intensity of urinary incontinence-a modified 1 h pad test. The obtained results have an application value giving the possibility of using effective therapy with sonofeedback in women in whom the recommended electrostimulation method cannot be used due to health and behavioral reasons.Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Komiya, S., et al. (2022). "The novel oral gonadotropin-releasing hormone receptor antagonist relugolix is a new option for controlled ovarian stimulation cycles." Reproductive Medicine and Biology 21(1): e12448.
	Purpose: Relugolix is an oral gonadotropin-releasing hormone antagonist (GnRHant), which was first introduced in 2019. This study investigated the effects of the conventional injectable GnRHant formulation and this new oral GnRHant formulation on controlled ovarian stimulation (COS) cycles. Method(s): Relugolix was administered in 126 cycles and conventional GnRHant injection was administered in 658 cycles (controls). The follicle stimulation was performed by an antagonist method, and for final oocyte maturation, recombinant human chorionic gonadotropin (rHCG), or gonadotropin-releasing hormone agonist (GnRHa), or both (dual trigger) were selected. The number of retrieved oocytes was counted and then they were evaluated for subsequent development up to cleavage stage. Result(s): The number of retrieved oocytes which was the primary outcome of this research was affected by the combination of GnRHant type and the final oocyte maturation agent. The combination of relugolix and a GnRHa trigger showed a significantly lower number of retrieved oocytes (p < 0.001) than the other combinations. Conclusion(s): Relugolix is a new option for COS cycles, but should be carefully combined with the final maturation agent. Clinical trial approval: This study was conducted after approval by the Medical Corporation Sankeikai Institutional Ethics Committee (approval number: 2019-34).Copyright © 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

Konci, R., et al. (2020). "Supplements to Conventional Treatment After Hysteroscopic Lysis of Intrauterine Adhesions: A Systematic Review." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 42(8): 984-1000.
	Intrauterine adhesions (IUAs) are a result of trauma to the basalis layer of the endometrium and may lead to clinical sequelae such as miscarriage, infertility, and menstrual irregularities. Hysteroscopy is recognized as the gold standard in diagnosis and management, although the optimal treatment after surgical intervention remains unclear. This review aimed to provide an update on the treatment options available after hysteroscopic adhesiolysis and to facilitate clinical management of patients with IUAs. To avoid duplicating previous work, the review focused on studies that compared various adjunctive postoperative treatments in patients receiving hormone therapy. Of 548 studies, 15 papers fit our criteria that compared post-resection treatment options in women with IUAs. Meta-analysis of the use of Foley catheter or amnion graft as an adjunctive therapy after adhesiolysis failed to show a statistical difference (odds ratio 1.55; 95% confidence interval 0.60-3.99). Meta-analysis could not be done for the 13 remaining studies as a result of extensive heterogeneity, bias, or non-comparable end points. The lack of a universal classification system for IUAs and the use of variable outcomes to measure the success of adjunctive treatment pose challenges in generating standard treatment recommendations. This review calls for the development of a universal classification system and studies with consistent parameters and end points to allow for the generation of standard treatment guidelines. On the basis of the available evidence, recommendation of specific adjunctive treatments after hysteroscopic adhesiolysis is unjustified. (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Koninckx, P. R., et al. (2022). "Reconsidering evidence-based management of endometriosis." Facts, views & vision in ObGyn 14(3): 225-233.
	Background: Without an adequate animal model permitting experiments the pathophysiology of endometriosis remains unclear and without a non-invasive diagnosis, information is limited to symptomatic women. Lesions are macroscopically and biochemically variable. Hormonal medical therapy cannot be blinded since recognised by the patient and the evidence of extensive surgery is limited because of the combination of low numbers of interventions of variable difficulty with variable surgical skills. Experience is spread among specialists in imaging, medical therapy, infertility, pain and surgery. In addition, the limitations of traditional statistics and p-values to interpret results and the complementarity of Bayesian inference should be realised.; Objectives: To review and discuss evidence in endometriosis management.; Materials and Methods: A PubMed search for blinded randomised controlled trials in endometriosis.; Results: Good-quality evidence is limited in endometriosis.; Conclusions: Clinical experience remains undervalued especially for surgery.; What Is New?: Evidence-based medicine should integrate traditional statistical analysis and the limitations of P-values, with the complementary Bayesian inference which is predictive and sequential and more like clinical medicine. Since clinical experience is important for grading evidence, specific experience in the different disciplines of endometriosis should be used to judge trial designs and results. Finally, clinical medicine can be considered as a series of experiments controlled by the outcome. Therefore, the clinical opinion of many has more value than an opinion.

Konski, A., et al. (2023). "Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203." Gynecologic Oncology 175: 176-181.
	Introduction: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments.; Methods: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05.; Results: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38).; Conclusion: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Konstantinopoulos Panagiotis, A., et al. (2022). "Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer." JAMA Oncology 8(9): 1317-1322.
	Importance: Although the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration-approved immunotherapy for mismatch repair proficient endometrial cancer [MMRP EC]) is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen, highlighting the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent MMRP EC.; Objective: To assess the potential positive outcomes and safety of the combination of the polyadenosine diphosphate-ribose polymerase inhibitor talazoparib and the programmed cell death ligand 1 (PD-L1) inhibitor avelumab in recurrent MMRP EC.; Design, Settings, and Participants: This investigator-initiated, open-label, single-arm, 2-stage, phase 2 study nonrandomized controlled trial patients at 4 institutions in the US. Key eligibility criteria included measurable disease, unlimited prior therapies, and all endometrial cancer histologies.; Interventions: Talazoparib, 1 mg, orally, daily, and avelumab, 10 mg/kg, intravenously, every 2 weeks, were administered until disease progression or unacceptable toxic effects.; Main Outcomes and Measures: Statistical considerations were developed for 2 coprimary objectives of objective response rate and rate of progression-free survival at 6 months, with a 2-stage design that allowed for early discontinuation for futility. Prespecified exploratory objectives included the association of immunogenomic features (determined by targeted-panel next-generation sequencing and immunohistochemistry) with activity.; Results: Thirty-five female patients (mean [SD] age, 67.9 [8.41] years) received protocol therapy; 9 (25.7%) derived clinical benefit after meeting at least 1 of the 2 coprimary end points. Four patients (11.4%) exhibited confirmed objective response rates (4 partial responses), and 8 (22.9%) survived progression free at 6 months. The most common grade 3 and 4 treatment-related toxic effects were anemia (16 [46%]), thrombocytopenia (10 [29%]), and neutropenia (4 [11%]); no patient discontinued receipt of therapy because of toxic effects. Tumors with homologous recombination repair alterations were associated with clinical benefit from treatment with avelumab and talazoparib. Tumor mutational burden, tumor-infiltrating lymphocytes, and PD-L1 status were not associated with clinical benefit.; Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that treatment with avelumab and talazoparib demonstrated a favorable toxic effect profile and met the predetermined criteria to be considered worthy of further evaluation in MMRP EC. Immunogenomic profiling provided insights that may inform ongoing and future studies of polyadenosine diphosphate-ribose polymerase and PD-L1 inhibitor combinations in endometrial cancer.; Trial Registration: ClinicalTrials.gov Identifier: NCT02912572.

Konstantinopoulos Panagiotis, A., et al. (2023). "A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(3): 599-608.
	Purpose: Estrogen receptor (ER)-positive endometrial cancers (ECs) are characterized by phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK)/RAS/β-catenin (CTNNB1) pathway alterations in approximately 90% and 80% of cases, respectively. Extensive cross-talk between ER, PI3K, and RTK/RAS/CTNNB1 pathways leads to both ligand-dependent and ligand-independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. We hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity in this setting.; Methods: We conducted a phase II, two-stage study of letrozole/abemaciclib in recurrent ER-positive EC. Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies; prior hormonal therapy was allowed. Primary end points were objective response rate by RECIST 1.1 and progression-free survival (PFS) rate at 6 months.; Results: At the data cutoff date (December 03, 2021), 30 patients (28 with endometrioid EC) initiated protocol therapy; 15 (50%) patients had prior hormonal therapy. There were nine total responses (eight confirmed), for an objective response rate of 30% (95% CI, 14.7 to 49.4), all in endometrioid adenocarcinomas. Median PFS was 9.1 months, PFS at 6 months was 55.6% (95% CI, 35.1 to 72), and median duration of response was 7.4 months. Most common ≥ grade 3 treatment-related adverse events were neutropenia (20%) and anemia (17%). Responses were observed regardless of grade, prior hormonal therapy, mismatch repair, and progesterone receptor status. Exploratory tumor profiling revealed several mechanistically relevant candidate predictors of response ( CTNNB1 , KRAS , and CDKN2A mutations) or absence of response ( TP53 mutations), which require independent validation.; Conclusion: Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER positive endometrioid EC.

Konstantinopoulos Panagiotis, A., et al. (2022). "A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer." Gynecologic Oncology 167(2): 213-225.
	Objective: High-grade serous ovarian cancer, the most frequent type of ovarian cancer, has a poor prognosis and novel treatments are needed for patients with platinum resistant/refractory disease. New therapeutic strategies targeting cell cycle checkpoints, including CHK1 inhibition with prexasertib, may help improve clinical response and overcome resistance.; Methods: Patients with ovarian cancer (N = 169) were assigned to 4 cohorts as part of the Phase 2 multicenter trial (NCT03414047): Cohort 1: platinum resistant, BRCA-wildtype with ≥3 lines prior therapy; Cohort 2: platinum resistant BRCA-wildtype with <3 lines prior therapy; Cohort 3: platinum resistant, BRCA-mutated with prior PARP inhibitor therapy; Cohort 4: platinum refractory, BRCA-mutated, or BRCA-wildtype with any number of prior therapy lines. The primary endpoint was objective response rate (ORR) and secondary endpoints included disease control rate (DCR), and safety. DNA from tumor biopsies was sequenced to identify biomarkers.; Results: The ORR in platinum resistant patients (Cohorts 1--3) was 12.1%, and 6.9% in platinum refractory patients. In platinum resistant patients, DCR was 37.1%, and consistent across cohorts. In platinum refractory patients, DCR was 31.0%. Consistent with the prexasertib mechanism of action, the most common treatment related adverse events of all grades included thrombocytopenia, neutropenia, fatigue, nausea, and anemia.; Conclusions: Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical characteristics, BRCA status, or prior therapies, including PARPi. There was no obvious correlation with genomic alterations in responders vs non-responders, emphasizing the need for alternative biomarker approaches for responder identification.; Competing Interests: Declaration of Competing Interest Nicoletta Colombo: Consultant/advisor: Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GlaxoSmithKline, Tesaro, Pfizer, BIOCAD, Immunogen, Mersana, Eisai, Oncxerna. Promotional ppeaker: AstraZeneca, Tesaro, Novartis, Clovis, MSD, GlaxoSmithKline, Eisai. Investigator/researcher: AstraZeneca, PharmaMar, Roche. Nonfinancial interests: Steering Committee member for ESMO Clinical Guidelines, Chair Scientific Committee ACTO onlus. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Konstantinopoulos Panagiotis, A., et al. (2024). "Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer." Gynecologic Oncology Reports 52: 101348.
	Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with AKT1, CTNNB1 and ESR1 hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414.; Competing Interests: Niya Xiong, Carolyn Krasner, Hannah Sawyer, Madeline Polak, Hope Needham, Megan Geddes, Lani Koppermann and Su-Chun Cheng have nothing to disclose. Megan Shea reports participation on a Data Safety Monitoring Board or Advisory Board from GSK and Eisai, and support for attending meetings and/or travel from Massachusetts Society of Clinical Oncology. Joyce Liu reports funding to Dana-Farber Cancer Institute for Trials on which she is the PI from 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, GlaxoSmithKline, Impact Therapeutics, Regeneron, Seagen, Vigeo Therapeutics, and Zentalis Pharmaceuticals; she also reports consulting and/or advisory board participation from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Daiichi Sankyo, Eisai, Genentech, GlaxoSmithKline, Regeneron Therapeutics and Zentalis Pharmaceuticals; she also reports being Co-chair of the NRG Oncology Ovarian Subcommittee and Co-chair of Tina’s Wish Scientific Advisory Board. Panagiotis Konstantinopoulos reports funding to Dana-Farber Cancer Institute from AstraZeneca, Pfizer, Eli Lilly, Bayer, Merck, GSK, Tesaro, Merck KGaA on trials which he is the PI; he also reports consulting and/or advisory board participation from Immunogen, GSK, Novartis, Alkermes, AstraZeneca, Bayer, Merck, Pfizer, Tesaro, Vertex, EMD Serono, Kadmon, BMS, IMV, Repare, Artios, Mersana. Ursula Matulonis reports consulting fees from Merck, GSK, AstraZeneca, Pfizer; payment on a CME lecture and slides on endometrial cancer from Med Learning Group; travel support from Immunogen to travel to an FDA launch meeting; she also reports fees from participation in advisory boards from Allarity, NextCure, Trillium, Agenus, Profound Bio, Novartis, Boerhinger Ingelheim, Rivkin Foundation, Ovarian Cancer Research Alliance, Clearity Foundation, Morphosy, CureLab, Eisai and fees from participation in Data Safety Monitoring Boards from Alkermes and Symphogen. Cesar Castro reports consulting fees from Qiagen, Teladoc and Advanced Medical. Elizabeth Lee reports funding to Dana-Farber Cancer Institute for a clinical Trial on which she is the PI from Merck; she also reports consulting fees from Aadi Biosciences and a GOG New Investigator Award for travel support to attend NRG Oncology conferences.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Author(s).)

Konstantinos, K., et al. (2023). "Transabdominal vs transvaginal cervical cerclage: a systematic review and meta-analysis."
	
Koochaksaraei Fatemeh, Y., et al. (2023). "Interventions promoting mental health dimensions in infertile women: a systematic review." BMC Psychology 11(1): 254.
	Background: Scientific developments have brought hope to infertile couples; however, the results are not always favorable. This makes women suffer psychological pressure. Therefore, previous studies have investigated the effectiveness of many psychological interventions but no research identified the most common psychological interventions. In this regard, the present review aimed to investigate different psychological interventions that promote mental health in infertile to identify the most frequent (common) ones.; Methods: In the present study, the search was carried out using appropriate keywords Infertility, psychological interventions, mental health, stress, anxiety, depression and women in the Google Scholar، Magiran، SID، Pubmed، Scopus، Science Direct، ProQuest، Web of Science databases and One of the leading websites in health- WHO with Persian and English languages and two operators of "AND" and "OR" between 2000 and 2021.; Results: First, 7319 articles were searched, 6948 articles of which were removed due to irrelevant subjects, and 31 articles were removed due to duplication. 340 abstracts were examined and the results of 60 articles were extracted. Two approaches (examining the type and content of intervention) were used to extract findings. The first approach indicated high diversity in psychological interventions, leading to the categorization of the interventions into 4 categories of cognitive behavioral therapy (CBT), mind-body interventions (MBI), stress management skills, and others. CBT and MBI and stress management skills were found as the most frequent promoting interventions for mental health in infertile women. The second approach indicated the differences in protocols (number of sessions and time of interventions).; Conclusion: Despite differences in protocol of interventions under study, the results of all articles revealed the effectiveness of interventions in improving infertile women's mental health; therefore, it is suggested to apply the most common psychological interventions based on scientific evidence (CBT, MBI, and stress management skills) along with infertility treatment methods. The results will help the specialists, policy-makers, and planners to select and implement the most appropriate psychological interventions for infertile women. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Koohpayeh Seyedeh, A., et al. (2021). "Effects of Rosa damascena (Damask rose) on menstruation-related pain, headache, fatigue, anxiety, and bloating: A systematic review and meta-analysis of randomized controlled trials." Journal of education and health promotion 10: 272.
	Recent studies have reported inconclusive results regarding the therapeutic effects of Rosa damascena on the outcomes of primary dysmenorrhea (PD) and premenstrual syndrome (PMS). Hence, this study is aimed to summarize the findings of randomized controlled trials (RCTs) regarding the effects of this treatment on menstruation-related pain as the primary outcome and menstruation-related headache, fatigue, anxiety, and bloating as the secondary outcomes. This study evaluated parallel-group and cross-over RCTs on aromatherapy, topical treatment, or oral intake of R. damascena products for the treatment groups versus placebo, nontreated, or conventional treatment groups. Seven electronic databases (Web of Science Core Collection, Scopus, Embase, CENTRAL, CINAHL, SID, and MagIran) and one search engine (PubMed) were searched from inception to January 15, 2021. Of 1468 trials found in the initial search, 983 potentially relevant articles were screened by title and abstract. After examining the full-text of 13 studies for compliance with the inclusion criteria, seven studies were considered eligible for this review. A random-effects model was used to pool the data; otherwise, a narrative summary was presented. The retrieved studies were conducted on females with PD or PMS, aged 18-35 years. The total sample size of the intervention and comparator arms was 276 and 272. The results showed that R. damascena had a nonsignificant alleviating effect on the menstruation-related pain (weighted mean difference [WMD]: -0.47; 95% confidence interval [CI]: -1.25, 0.31; P = 0.234). Such findings were also found for menstruation-related anxiety (WMD: -0.40; 95% CI: -0.91, 0.11; P = 0.125). However, the treatment significantly reduced the menstruation-related headache (WMD: -0.42; 95% CI: -0.74, -0.11; P = 0.008), fatigue (WMD: -0.48; 95% CI: -0.87, -0.09; P = 0.015), and bloating (WMD: -0.72; 95% CI: -1.21, -0.22; P = 0.005). Since R. damascena had no significant effects on menstruation-related pain and anxiety, further studies with improved methodological quality are suggested to evaluate the effects of the treatment on these symptoms, using different dosages and durations.; Competing Interests: There are no conflicts of interest. (Copyright: © 2021 Journal of Education and Health Promotion.)

Koole Simone, N., et al. (2022). "Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer: Results from the phase III OVHIPEC trial." International journal of cancer 151(8): 1394-1404.
	The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence-free (RFS) and overall survival (OS) in patients with stage III ovarian cancer. Homologous recombination deficient (HRD) ovarian tumors are usually more platinum sensitive. Since hyperthermia impairs BRCA1/2 protein function, we hypothesized that HRD tumors respond best to treatment with HIPEC. We analyzed the effect of HIPEC in patients in the OVHIPEC trial, stratified by HRD status and BRCAm status. Clinical data and tissue samples were collected from patients included in the randomized, phase III OVHIPEC-1 trial. DNA copy number variation (CNV) profiles, HRD-related pathogenic mutations and BRCA1 promotor hypermethylation were determined. CNV-profiles were categorized as HRD or non-HRD, based on a previously validated algorithm-based BRCA1-like classifier. Hazard ratios (HR) and corresponding 99% confidence intervals (CI) for the effect of RFS and OS of HIPEC in the BRCAm, the HRD/BRCAwt and the non-HRD group were estimated using Cox proportional hazard models. Tumor DNA was available from 200/245 (82%) patients. Seventeen (9%) tumors carried a pathogenic mutation in BRCA1 and 14 (7%) in BRCA2. Ninety-one (46%) tumors classified as BRCA1-like. The effect of HIPEC on RFS and OS was absent in BRCAm tumors (HR 1.25; 99%CI 0.48-3.29), and most present in HRD/BRCAwt (HR 0.44; 99%CI 0.21-0.91), and non-HRD/BRCAwt tumors (HR 0.82; 99%CI 0.48-1.42), interaction P value: 0.024. Patients with HRD tumors without pathogenic BRCA1/2 mutation appear to benefit most from treatment with HIPEC, while benefit in patients with BRCA1/2 pathogenic mutations and patients without HRD seems less evident. (© 2022 UICC.)

Koole, S. N., et al. (2021). "Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer." European Journal of Surgical Oncology 47(1): 101‐107.
	Introduction: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improves recurrence‐free (RFS) and overall survival (OS) in patients with FIGO stage III ovarian cancer. We evaluated the effect of HIPEC on patient's health‐related quality of life (HRQoL) in the OVHIPEC trial. Materials and methods: OVHIPEC was a multicentre, open‐label, randomized phase III trial for patients with stage III ovarian cancer. Patients were randomly assigned (1:1) to receive interval CRS with or without HIPEC with cisplatin. HRQoL was assessed using the EORTC QLQ‐C30, and the ovarian (QLQ‐OV28) and colorectal cancer (QLQ‐CR38) modules. HRQoL questionnaires were administered at baseline, after surgery, after end of treatment, and every three months thereafter. HRQoL was a secondary endpoint, with the prespecified focus on the QLQ‐C30 summary score and symptom scores on fatigue, neuropathy and gastro‐intestinal symptoms. HRQoL was analysed using linear and non‐linear mixed effect models. Results: In total, 245 patients were randomized. One‐hundred‐ninety‐seven patients (80%) completed at least one questionnaire. No significant difference over time in the QLQ‐C30 summary scores was observed between the study arms (p‐values for linear and non‐linear growth: p > 0.133). The pattern over time for fatigue, neuropathy and gastro‐intestinal symptoms did not significantly differ between treatment arms. Conclusion: The addition of HIPEC to interval CRS does not negatively impact HRQoL in patients with stage III ovarian cancer who are treated with interval CRS due to the extent of disease. These HRQoL results, together with the improvement in RFS and OS, support the viability of HIPEC as an important treatment option in this patient population. ClinicalTrials.gov number: NCT00426257. EudraCT number: 2006‐003466‐34.

Kop, P. A. L., et al. (2022). "Intracervical insemination versus intrauterine insemination with cryopreserved donor sperm in the natural cycle: a randomized controlled trial." Human reproduction (Oxford, England) 37(6): 1175-1182.
	Study Question: Is intracervical insemination (ICI) non-inferior to IUI with cryopreserved donor sperm in the natural cycle in terms of live birth?; Summary Answer: ICI with cryopreserved donor sperm in the natural cycle was inferior to IUI in terms of live birth.; What Is Known Already: Both ICI and IUI in the natural cycle are performed as first-line treatments in women who are eligible for donor sperm treatment. High-quality data on the effectiveness of ICI versus IUI with cryopreserved donor sperm in the natural cycle in terms of live birth is lacking.; Study Design, Size, Duration: We performed an open-label multicentre randomized non-inferiority trial in the Netherlands and Belgium.; Participants/materials, Setting, Methods: We randomly allocated women who were eligible for donor sperm treatment with cryopreserved donor semen to six cycles of ICI in the natural cycle or six cycles of IUI in the natural cycle. The primary outcome was conception within 8 months after randomization leading to a live birth. Secondary outcomes were ongoing pregnancy, multiple pregnancy, clinical pregnancy, miscarriage and time to conception leading to live birth. We calculated relative risks (RRs) and risk differences (RDs) with 95% CI. Non-inferiority would be shown if the lower limit of the 95% RD CI was <-12%.; Main Results and the Role of Chance: Between June 2014 and February 2019, we included 421 women, of whom 211 women were randomly allocated to ICI and 210 to IUI. Of the 211 women allocated to ICI, 2 women were excluded, 126 women completed treatment according to protocol and 75 women did not complete 6 treatment cycles. Of the 210 women allocated to IUI, 3 women were excluded, 140 women completed treatment according to protocol and 62 women did not complete 6 treatment cycles. Mean female age was 34 years (SD ±4) in both interventions. Conception leading to live birth occurred in 51 women (24%) allocated to ICI and in 81 women (39%) allocated to IUI (RR 0.63, 95% CI: 0.47 to 0.84). This corresponds to an absolute RD of -15%; 95% CI: -24% to -6.9%, suggesting inferiority of ICI. ICI also resulted in a lower live birth rate over time (hazard ratio 0.58, 95% CI: 0.41-0.82). Our per-protocol analysis showed that, within the 8 months treatment horizon, 48 women (38%) had live births after ICI and 79 women (56%) had live births after IUI (RR 0.68, 95% CI: 0.52-0.88; RD -18%, 95% CI: -30% to -6%).; Limitations, Reasons for Caution: The study was non-blinded owing to the nature of the interventions. We consider it unlikely that this has introduced performance bias, since pregnancy outcomes are objective outcome measures.; Wider Implications of the Findings: Since ICI in the natural cycle was inferior to IUI in the natural cycle with cryopreserved donor sperm in terms of live birth rate, IUI is the preferred treatment.; Study Funding/competing Interest(s): This trial received funding from the Dutch Organization for Health Research and Development (ZonMw project number 837002407). B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437), reports consultancy for ObsEva and has received research funding from Guerbet, Ferring and Merck. The other authors do not declare a COI.; Trial Registration Number: NTR4462.; Trial Registration Date: 11 March 2014.; Date of First Patient’s Enrolment: 03 June 2014. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Kopcsay, K. S., et al. (2022). "Treatment of refractory overactive bladder with OnabotulinumtoxinA vs PTNS: TROOP trial." International Urogynecology Journal 33(4): 851-860.
	Introduction and hypothesis: We hypothesized that patients with refractory overactive bladder (rOAB) have similar improvement with percutaneous tibial nerve stimulation (PTNS) and OnabotulinumtoxinA (BTX). Method(s): This multicenter cohort study compared BTX and PTNS in women with rOAB. Baseline information included Overactive Bladder Questionnaire (OABq) short form, Urinary Distress Inventory-6 (UDI-6), and voiding diary. Primary outcome was cure, defined as "very much better" or "much better" on the Patient Global Impression of Improvement (PGII) AND a reduction in OABq symptom severity scale (SSS) >=10 at 3 months after treatment. Assuming 80% power to detect a ten-point difference in OABq-SSS, 80 participants were required per group. Result(s): A total of 150 patients were enrolled; 97 completed 3 months of therapy and were included. At baseline, BTX patients had more detrusor overactivity (70% vs 40%, p = 0.025), urgency incontinence (UUI; OABq-SSS#6 4 vs 3, p = 0.02, SSS 65 vs 56, p = 0.04), but similar health-related quality of life (HRQL 49 vs 54, p = 0.28), voids (7 vs 8, p = 0.13), and UUI episodes (2 vs 2, p = 1.0). At 3 months, cure rates were similar: BTX 50% vs PTNS 44.2% (p = 0.56). Both groups had improved SSS (-37 vs -29, p = 0.08) and HRQL (31 vs 24, p = 0.14). Patients receiving BTX had a greater improvement in urgency (DELTAOABq-SSS#2-3 vs -2; p = 0.02) and UUI (DELTAOABq-SSS#6-2 vs -1; p = 0.02). No characteristics were predictive of cure. Conclusion(s): BTX resulted in significantly greater improvement in urgency and UUI than PTNS, but no difference in success based on PGII and OABq-SSS, which may be due to a lack of power.Copyright © 2021, The International Urogynecological Association.

Kopmeiners Emma, H. M., et al. (2023). "Effect of early postpartum EMDR on reducing psychological complaints in women with a traumatic childbirth experience." Journal of Psychosomatic Obstetrics and Gynaecology 44(1): 2229010.
	This pilot study investigated the feasibility of postpartum Eye Movement Desensitization and Reprocessing (EMDR) for improving posttraumatic stress disorder (PTSD) symptoms, and its association with work absence, relationship difficulties, and development of psychiatric disorders in women with a traumatic childbirth experience who do not meet all criteria for PTSD. A randomized controlled study was conducted among 20 women (EMDR (N=11) vs. care as usual (CAU) (N=9)) who reported a traumatic birth. Outcomes were measured by questionnaires and a semi-structured interview. The results showed improvement of trauma-related psychological complaints for all women. EMDR appears to be more effective in reducing PTSD symptoms than CAU. Moreover, EMDR showed a small positive effect on work absence due to factors related to the traumatic childbirth experience. Results from the questionnaires were substantiated by interviews. However, due to the small size of the study, no statistically significant differences were found. In addition, no differences were found for relationship difficulties and development of psychiatric disorders. In conclusion, women with a traumatic birth experience may benefit from EMDR, even if they do not qualify for a diagnosis of PTSD. This study could be a starting point for future research aimed at early treatment that reduces trauma-related psychological complaints in postpartum women.

Korelo Raciele Ivandra, G., et al. (2022). "Effects of Auriculotherapy on treatment of women with premenstrual syndrome symptoms: A randomized, placebo-controlled clinical trial." Complementary Therapies in Medicine 66: 102816.
	Objective: This study aimed to investigate the effect of auriculotherapy on the intensity of physical and mood Premenstrual syndrome (PMS) symptoms.; Design: Single-blind randomized, placebo-controlled clinical trial.; Setting: Federal University of Parana, Curitiba, Brazil.; Intervention: Ninety-one women were randomly assigned to Auriculotherapy (AG), Placebo (PG), and Control (CG) groups. The intervention was 8 weeks long, done once per week. At each session in AG the microneedles were placed in seven points related to PMS symptoms (Anxiety; Endocrine; Muscle relaxation; Analgesia; Kidney; Shen Men; and Sympathetic). At PG the microneedles also were placed in seven points but unrelated to PMS symptoms (Tonsils; Vocal cords; Teeth; Eyes; Allergy; Mouth; and External nose).; Main Outcome Measures: Assessments of PMS symptoms (Premenstrual Syndrome Screening Tool), musculoskeletal pain (Nordic Musculoskeletal Questionnaire), anxiety (Beck Anxiety Inventory), and quality of life (WHOQOL-Bref) were done at baseline, before the 5th session, after program completion, and a month follow-up.; Results: The AG and PG showed significantly lower scores of PMS symptoms, musculoskeletal pain, and anxiety. On the quality of life and follow-up analysis, the significance was observed only in PG.; Conclusion: Auriculotherapy can be used as adjunctive therapy to reduce the physical and mood PMS symptoms. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Koren, G., et al. (2020). "Fetal safety of medications used in treating infertility [RETRACTED]." Expert review of clinical pharmacology: 1-10.
	INTRODUCTION: The medications used in assisted reproduction are given before and during early pregnancy, and hence, they may potentially result in adverse fetal effects. In this review we present an updated account of their fetal safety and discuss methodological challenges in interpretation of existing data. AREAS COVERED: The fetal safety/risks of clomiphene citrate, aromatase inhibitors, metformin, gonadotropins and progestins are discussed. We searched PubMed, EMBASE, Cochrane, Google and Google Scholar from inception to April 30, 2020 for publications pertinent to our topic. EXPERT OPINION: There are several major challenges in studying fetal safety of medications used in assisted reproduction. The fact that the rates of congenital malformations among infertile women giving birth spontaneously is higher than the rates among healthy women conceiving spontaneously. In most clinical studies of assisted reproduction, the primary endpoint is the success in inducing pregnancy, neglecting to report pregnancy outcome and adverse neonatal event. As an example for this reality, it has been estimated that between 1977 to 2005 around 10 million pregnancies were treated with dydrogesterone (DYD) yet till 2019 only very few studies, with a total sample size of less than 600 were reported with regards to fetal safety.

Korevaar Tim, I. M. and R. Dhillon-Smith (2022). "Levothyroxine treatment in euthyroid women positive for thyroid peroxidase antibodies and recurrent pregnancy loss." The lancet. Diabetes & endocrinology 10(5): 299-301.
	Competing Interests: TIMK reports lecture fees from Berlin-Chemie, Goodlife Healthcare, EXCEMED, Merck, IBSA, and Quidel, and currently serves as the co-chair of the 2023 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Preconception, Pregnancy and the Postpartum guideline committee. RD-S serves as the Fertility and Assisted Reproduction working group coordinator of the 2023 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Preconception, Pregnancy and the Postpartum guideline committee.

Korkem, Y., et al. (2024). "The effect of long-term, regular yoga on the pain and quality of life in women with premenstrual syndrome: A randomized controlled, single-blinded trial." Health Care for Women International: 1-13.
	Premenstrual syndrome (PMS) has been known to have emotional, physical, and behavioral effects in reproductive age. To evaluate the effects of premenstrual syndrome (PMS) on pain and quality of life in women, who perform regular yoga exercises in the long term. 30 women with PMS and 30 control (31.17+/-5.28years old) participated in this randomized controlled, single blinded study. The demographics of the PMS and control groups were similar (p<0.05). A significant difference was found in a depressive mood, anxiety, fatigue, pain, depressive thoughts, sleeping habits subscales, and total scores of the PMSS, WHOQOL-BREF scale, and VAS scores between yoga and control groups (p<0.05). It is determined that long-term and regular yoga practice for women with PMS will improve their, PMS symptoms, quality of life, and pain level.

Korotkikh, N. V., et al. (2023). "The practical significance of using Canephron N medication for radiation cystitis prevention in patients undergoing radiation/chemoradiation therapy." Onkourologiya 19(3): 126-132.
	Background. With increasing life expectancy in cervical cancer patients, new medical and social problems associated with radiation therapy become apparent. The combination of radiation therapy and chemotherapy is an important therapeutic component in treatment of malignant neoplasms of the genital area in women, but the frequency and severity of side effects has been increasing. Radiation complications occur in 20-50 % of patients. In 5 % of patients, they can represent a severe and potentially life-threatening condition. Prevention of negative effects on the genitourinary system in cervical cancer patients receiving radiation therapy on the pelvis is a matter of importance. Aim. To evaluate the clinical efficacy of a phytotherapeutic preparation Canephron N containing centaury, lovage root, rosemary leaves in the prevention of radiation cystitis during chemoradiotherapy in patients with advanced cervical cancer. Materials and methods. The study included 60 patients with locally advanced cervical cancer receiving radical chemoradiotherapy. The patients were divided into 2 groups: treatment group consisting of patients receiving phytotherapeutic preparation Canephron N for prevention of radiation complications, and control group consisting of patients not receiving symptomatic treatment. The treatment results were evaluated using questionnaires, clinical, laboratory and instrumental studies. The obtained data were compared with the results of treatment of the control group which were not prescribed a medication for prevention of urological complications. Results and conclusion. The use of Canephron N in accompanying therapy had significantly decreased the risk and incidence of radiation cystitis.Copyright © 2023 ABC-press Publishing House. All rights reserved.

Kose, C., et al. (2023). "Management of Borderline Ovarian Tumours: Tertiary Centre Experience from Turkey." Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 33(10): 1201-1203.
	This study aimed to analyse the management protocols, surgical approaches, and outcomes of the women with Borderline ovarian tumours (BOT) at Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey. One hundred and seventy-seven patients diagnosed with serous and mucinous BOT were enrolled in the study. Demographic, clinical, and pathological data were reviewed retrospectively from the medical records. The patients were divided into two groups according to surgical interventions: Laparoscopy group (n=50) and Laparotomy group (n=127). Treatment was conservative in 107 (60.5%) patients. Mean age at diagnosis (48.69 ± 12.52 vs. 41.1±11.66 years, p<0.001), tumour size (84.13 ± 51.85 mm vs. 67.1 ± 34.78 mm, p = 0.013), and number of postmenopausal patients (n = 55 vs. 9, p = 0.002) were significantly higher in the Laparotomy group. There were no significant differences in the rates of intraoperative cyst rupture (22% vs. 18%, p = 0.120) and recurrence (2.25% vs. 5.05%, p = 0.760). There was no difference between radical vs. conservative surgery and laparotomy vs. laparoscopy in terms of recurrences. In appropriate cases, the conservative treatment and laparoscopy may be preferred. Key Words: Borderline ovarian tumour, Laparoscopy, Laparotomy.

Kosei, H., et al. (2022). Pembrolizumab and Bevacizumab With Chemotherapy Followed by Pembrolizumab, Bevacizumab and Olaparib in Recurrent Ovarian Cancer.
	No Results Available Biological: pembrolizumab|Drug: olaparib|Biological: bevacizumab|Drug: carboplatin|Drug: paclitaxel|Drug: docetaxel Two-year progression-free survival rate|Progression-Free Survival (PFS)|PFS in maintenance period by chemotherapy responder|Objective Response Rate (ORR)|Disease Control Rate (DCR)|Duration of Response (DOR)|One-year progression-free survival rate|Overall Survival (OS)|Incidence of adverse events Female Phase 2 35 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment SaINT-ov02 November 30, 2024

Kosinska, K., et al. (2023). "Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): Study protocol for a multicentre, non-blinded, randomised controlled trial." BMJ Open 13(6): e071564.
	Introduction Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. Methods and analysis This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. Ethics and dissemination The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. Trial registration NCT05268640.Copyright © 2023 Authors. All rights reserved.

Kossakowski, K., et al. (2023). "Krytyczne spojrzenie na nowe mozliwosci zastosowania terapeutycznego statyn - podsumowanie aktualnego stanu wiedzy." Farmacja Polska 79(5): 297-315.
	Hypercholesterolemia is a condition characterized by total cholesterol levels exceeding 200 mg/dl. A breakthrough in its treatment was the introduction of the first representative of the status - lovastatin. The mechanism of their action relies on inhibition of the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme responsible for converting HMG-CoA to mevalonic acid, the main substrate in the synthesis of endogenous cholesterol. The progress of experimental and clinical studies on action statins indicates a number of other biological properties of this group of compounds, and thus their pharmacological potential. The possibility of their use in the pharmacotherapy of cardiovascular diseases, hyperandrogenism in women with polycystic ovary syndrome (PCOS), osteoporosis, type 2 diabetes, neurodegenerative diseases, or cancer has been so far highlighted. The aim of this paper was to systematize the knowledge of statin drugs in terms of the progress of studies on their biological activity indicating the possibility of their potential use in the treatment of diseases other than those related to the cardiovascular system, along with verification of their safety profile and demonstrated adverse effects (DN) as a result of their intake. The literature review was conducted by a screening of the following scientific databases - PubMed and Google Scholar (the analysis lasted from March 2022 to February 2023). The keywords used for searching were disease-related and DN-related. Statins have shown potential to alleviate symptoms of androgen excess in women suffering from polycystic ovary syndrome (PCOS). Studies relating to their effect on the treatment of Alzheimer's disease and dementia indicate a reduction in progressive neurodegenerative changes, and thus suggest their potential use in the prevention and treatment of comorbid cardiovascular disease. Moreover, statins tend to reduce morbidity, increase survival, and alleviate the progression of cancer. The results of studies of the effects of these drugs on the possibility or development of Parkinson's disease, osteoporosis and the etiology of muscle symptoms appear to be inconsistent in the relationship of their benefits to DN. Unfortunately, it seems that they have also led to disturbances in carbohydrate metabolism and increased the risk of type II diabetes mellitus (NODM). Studies on the effect of the nocebo effect during statin therapy on the frequency with which patients experience DN have confirmed the presence of this effect. Analysis of the collected studies shows considerable potential for expanding the current therapeutic indications of the drugs in question. However, further randomized controlled trials are required to determine the precise effective dose, duration of therapy for a specific statin.Copyright © The Author(s), 2023.

Kotha Nikhil, V., et al. (2023). "A randomized patient education trial investigating treatment-related distress and satisfaction with the use of an at-home gynecologic brachytherapy educational video." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(7): 1125-1131.
	Background: Physician explanation of gynecologic brachytherapy can be overwhelming or induce patient anxiety, and may be time-constrained given clinical limitations. We report the first randomized trial of an educational video intervention in gynecologic brachytherapy on patient-reported outcomes.; Methods: Between February 2020 and January 2022, 80 gynecologic cancer patients prescribed brachytherapy were randomly assigned to either standard informed consent (Arm A) or a supplemental 16 min brachytherapy educational video (https://vimeo.com/403385455/d0716e3cc8) via the internet (Arm B). Primary outcome was treatment-related distress (National Comprehensive Cancer Network (NCCN) distress scale scored 0 (no distress) to 10 (maximum distress)). Secondary outcome was patient satisfaction (summated Likert-scale scored 11-55). Surveys were administered at baseline, after first treatment, and prior to brachytherapy completion.; Results: All patients completed the prescribed brachytherapy. In Arm B, 19/40 (48%) patients and 10/40 (25%) patients' family/friends viewed the video. For patients that completed all surveys (Arm A n=29, Arm B n=28), there was no difference between arms in the sociodemographic, clinical, or treatment variables. Distress scores were low at baseline (Arm A median 4, Arm B median 4, p=0.65) and there was no detectable change in distress between arms on surveys 1 and 2 (β 0.36, p=0.67) or surveys 1 and 3 (β -1.02, p=0.29) in multivariable analysis. Satisfaction scores were high at baseline (Arm A median 54, Arm B median 54.5, p=0.64) and there was no detectable change in satisfaction between arms on surveys 1 and 2 (β 0.22, p=0.93) or surveys 1 and 3 (β 0.63, p=0.85) in multivariable analysis.; Conclusions: Among patients randomized to an educational video tool for gynecologic brachytherapy, approximately 50% of the cohort and 25% of the cohort's family/friends used the video. Overall, patients had low distress scores and high satisfaction scores with no significant differences between the standard and video intervention arms. Further work is needed to understand factors contributing to gynecologic brachytherapy anxiety.; Trial Registration Number: NCT04363957.; Competing Interests: Competing interests: DB received honorarium from Varian Medical Systems outside the submitted work. DR received honorarium from Vision RT and Radformation outside the submitted work. DS serves as a consultant for Merit Medical Inc and Varian Medical Systems outside the submitted work. JM serves as a consultant for Astra Zeneca, NRG Oncology, GOG Foundation, Varian Medical Systems, Primmune, Merck; serves as co-chair for NRG Oncology Cervix Co-Chair; serves as board member for GOG Foundation outside the submitted work. All remaining authors have declared no conflicts of interest. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Kotlyar Alexander, M. and B. Seifer David (2023). "Women with PCOS who undergo IVF: a comprehensive review of therapeutic strategies for successful outcomes." Reproductive biology and endocrinology : RB&E 21(1): 70.
	Polycystic ovarian syndrome (PCOS) is a widespread syndrome that poses unique challenges and constraints to the field of assisted reproductive technology. This condition is the most common cause of anovulation among infertile couples. Debate exists over the best therapeutic course of action when patients with PCOS proceed to IVF. In this review, we evaluate the best-performing and safest methods of IVF preparation, ovarian stimulation, trigger method for maturation of stimulated egg growth, and planning for embryo transfer. Pre-IVF considerations include being aware of individual AMH and vitamin D levels as well as BMI prior to selecting an ovarian stimulation protocol. Numerous supplements such as myo-inositol complement the benefits of lifestyle change and may enhance IVF performance including oocyte yield and pregnancy rate. Concerning stimulation protocols, antagonist cycles with the judicious use of GnRH agonist trigger, pre-treatment with metformin and vitamin D repletion may help mitigate the accompanied risk of ovarian hyperstimulation syndrome (OHSS). Following ovarian stimulation, PCOS patients typically undergo programmed frozen embryo transfer (FET) cycles which are more conducive for women with irregular cycles, but likely carry a higher risk of hypertensive disorders of pregnancy. However, newer stimulated FET protocols using Letrozole may offer improved outcomes. Overall, patients with PCOS require careful individual tailoring of their IVF cycle to achieve optimal results. (© 2023. The Author(s).)

Koufopoulos, N., et al. (2019). "Primary squamous cell carcinoma of the ovary. Review of the literature." Journal of B.U.ON. : official journal of the Balkan Union of Oncology 24(5): 1776-1784.
	PURPOSE: Primary squamous cell carcinoma (SCC) of the ovary is rare. Most cases arise from a cystic teratoma or less frequently from Brenner tumor or endometriosis. We reviewed 36 cases of primary ovarian SCC reported in the literature including a case diagnosed and treated in our institution. METHODS: Data was collected by using the key-words "primary squamous cell carcinoma" and "ovary" on Google Scholar and PubMed in April 2018. All reviewed cases were analyzed according to diagnosis, surgical approach, adjuvant therapy and outcome. RESULTS: To date 23 articles presenting 36 cases of primary ovarian SCC are reported. Nine patients had stage I, 8 stage II, 11 stage III and 5 stage IV disease, whereas 3 patients had in situ carcinoma. All patients underwent surgery (mainly hysterectomy with bilateral salpingo-oophorectomy). Adjuvant therapy was reported in 24 patients, 15 of which received chemotherapy, 6 radiotherapy and 3 a combination of both. Chemotherapy regimens were similar to the ones used in ovarian carcinoma (more often platinum plus paclitaxel). Follow-up period was in general short and survival varied between 9 days and 14 years, depending on the stage at diagnosis. CONCLUSIONS: Primary ovarian SCC is a rare entity with poor prognosis, compared to serous carcinoma. Treatment is usually extrapolated from classical ovarian carcinoma algorithms, including surgical management combined with adjuvant chemotherapy with or without radiotherapy. Further investigations are needed to define optimal treatment, such as chemotherapy regimens and the role of radiotherapy and lymph node dissection.

Kouzuma, N., et al. (2022). "Heart Rate and Autonomic Nervous System Activity Relationship During Acupuncture Associated with Postural Change and Effect on Menopausal Symptoms: A Prospective Randomized Trial." Medical acupuncture 34(5): 299-307.
	Objective: The autonomic nervous system (ANS) has been assessed using heart rate variability (HRV), and HRV has been used to evaluate acupuncture. This study investigated the relationship between heart rate (HR) and ANS activity during acupuncture and postural change.; Materials and Methods: Subjects (48 menopausal women) were assigned randomly to acupuncture and sham groups. Japanese-style acupuncture at 7 points was performed weekly for 4 weeks. For sham treatment an acupuncture tube was pressed at the same 7 points. Measurements of HR were taken at: stage 1 (supine position before acupuncture; control); stage 2 (acupuncture for 10 minutes), and stage 3 (after standing for 10 minutes). During the experiments, the following HRV indices were obtained: high (0.15 - 0.40 Hz) frequency (HF) power and low frequency (LF) power/high frequency power ratio (LF/HF) as an index of the parasympathetic nervous system activity and sympathetic nervous system activity, respectively. Participants' menopausal symptoms were assessed using a visual analogue scale.; Results: Reduction in HR during needle insertion and removal was significantly lower than that of retention ( P < 0.01). There was a significant positive correlation between HR reduction during insertion and removal of needles ( r = 0.732; P = 0.000). HR decreased by ≥5% in 79% (19/24) of the acupuncture-treated subjects. HF was increased significantly during acupuncture, while LF/HF decreased during standing. Menopausal symptoms were alleviated significantly.; Conclusions: Stimulation during acupuncture-needle insertion and removal regulated ANS function, causing a decreased HR. This technique relieve patients' menopausal symptoms.; Competing Interests: No financial conflicts of interest exist. (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Kovachev, S. M. and M. S. Kovachev (2021). "The role of perioperative ureteral stenting for urologic complications in radical surgery of cervical cancer." Urologia 88(4): 348-354.
	INTRODUCTION: This study aimed to establish the urologic complications of radical type C2 hysterectomy in cervical cancer patients with or without ureteral stenting. METHODS: This prospective randomized study included 76 (100%) patients with clinically and pathologically established cervical cancer stages I and II treated with radical type C2 hysterectomy with pelvic lymph node dissection for the last 5 years (2014-2019). Patients were randomized into two groups (2:1 ratio): group II received perioperative ureteral stenting (n = 24, 31.6%) and group I did not (n = 52, 68.4%). Urologic complications observed during follow-up include intraoperative ureter and urinary bladder lesions and postoperative ureterovaginal and vesicovaginal fistulas. RESULTS: Of the 52 patients in group I who underwent surgery for cervical cancer, urologic complications were observed in 8 (10.5%) patients, 2 (2.6%) of whom underwent preoperative radiation therapy. In group II, urologic complications were observed in 2 (2.6%) patients, of which 1 (1.3%) received preoperative radiation therapy. Intraoperative urologic complications in group I (6.6%) included 3 (3.9%) ureteral lesions cases and 2 (2.6%) cases of urinary bladder lesions, wherein 1 patient received preoperative radiation therapy. One case of (1.3%) urinary bladder lesion was observed in group II. Postoperative complications were observed in 3 patients (3.9%) in group I, including 2 (2.6%) ureterovaginal fistula cases, wherein 1 (1.3%) patient received preoperative radiation therapy, and 1 (1.3%) case of vesicovaginal fistula. In group II, 1 (1.3%) patient who received perioperative radiotherapy developed postoperative vesicovaginal fistula. DISCUSSION: Urologic complications are extremely common during and after radical surgery (hysterectomy type C2) for cervical cancer. The cervical cancer stage had a significant effect on intra- and postoperative urologic complication rates in this study; however, no such effect was observed for preoperative radiation therapy and ureteral stenting, and significant differences were observed between the two study groups.

Kovacs, P., et al. (2023). "Comparing pregnancy rates following ovarian stimulation with follitropin-Δ to follitropin -α in routine IVF: a retrospective analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 280: 22‐27.
	Study objectives: Follitropin‐Δ, a new recombinant follicle stimulation hormone, uses a fixed daily dose producing a predictable ovarian response while using less gonadotropins compared to follitropin‐α. We report clinical outcomes comparing each in the routine IVF setting and further compare qualified to disqualified subjects based on previous randomized controlled trial (RCT) inclusion criteria. Study design: Retrospective analysis of all cycles performed by a single provider between January 2020 to January 2021. All IVF cycles without patient inclusion–exclusion criteria were considered for the analysis. Clinical outcomes in two groups (follitropin‐Δ vs follitropin‐α ± 75 IU human menopausal gonadotropin (hMG) in expected poor responders) were compared. In addition, comparisons were made between qualified versus disqualified subgroups. Results: No differences in baseline demographics, number of MII oocytes, fertilization/MII oocyte, percent of good quality embryos were noted. Compared to those using follitropin‐α, follitropin‐Δ resulted in lower daily (170 vs 211 IU/d, p = 0.002) and total Gn used (1739 vs 2194 IU, p = 0.003). Optimal range response (8–14 oocytes) (22/44 [50 %] vs 78/203 [38.6 %]; p = 0.10) and fresh (fCP) and cumulative clinical pregnancy (cCP) rates per transfer (29.5 % vs 24.1 % and 35 % vs 25.1 %, p = 0.08) were similar between groups. Based on previous RCTs, those who would have qualified compared to those who would have disqualified, patients using follitropin‐Δ were just as likely to have an optimal oocyte response (qualified: 48 % vs disqualified: 57.1 %) and resulted in similar cCP (41.4 % vs 25 %, p‐0.23). Conclusions: While follitropin‐Δ requires less daily and total dosing compared to follitropin‐α, optimal range of retrieved oocytes and clinical outcomes appear to be comparable. Using RCT inclusion criteria, similar findings were noted in those who would have qualified compared to disqualified patients.

Kovacs, Z., et al. (2024). "The Effect of Aviva Exercise Intervention on Pain Level and Body Awareness in Women with Primary Dysmenorrhea." Medicina (Kaunas, Lithuania) 60(1).
	Background and Objective: Primary dysmenorrhea (PD) is one of the most common clinical disorders in women of reproductive age. Our aim was to examine whether a twice-weekly thirty-minute Aviva exercise intervention could result in improvements in pain level and body awareness in patients with PD. Material(s) and Method(s): In our prospective observational trial, the observation period included two consecutive menstrual cycles and the period of the next menstrual bleeding. The first menstrual bleeding period was the first measurement time (T1), the second was the second measurement time (T2), and the third was the third measurement time (T3) in a total of 78 volunteers. The primary endpoint was the change in the level of menstrual pain according to the Numeric Rating Scale (NRS) questionnaire between the intervention group (IG) and the control group (CG) at T1, T2, and T3. In this study, the secondary outcomes were the differences between the IG and CG regarding the different subscales of the Hungarian version of the Body Awareness Questionnaire (BAQ-H) at T1, T2, and T3; the Borg scale results of the IG; and adherence to the intervention. Statistical tests such as independent-sample t-tests, chi-square tests, Pearson's linear correlation coefficient, and repeated-measure ANCOVA were used for the analyses. Result(s): In total, 78 volunteers were enrolled: 40 persons in the IG and 38 in the CG. There was a significant change in the level of menstruation pain according to the NRS questionnaire between the IG and CG (p < 0.001). There was no significant difference between the IG and CG regarding the different subscales of the BAQ-H. Only in the case of the "Note responses or changes in body process" subscale of the BAQ-H was there a trend-like effect from the Aviva exercises (p = 0.086). Conclusion(s): The Aviva exercise could contribute to pain relief from PD. Regarding body awareness, no significant difference was found between the two groups. Due to the short detection period and prospective observational design, our results are preliminary and need to be confirmed in larger clinical trials.

Kovács, Z., et al. (2023). "The Effect of Exercise on Pulsatility Index of Uterine Arteries and Pain in Primary Dysmenorrhea." Journal of Clinical Medicine 12(22).
	Background: Primary dysmenorrhea (PD) is one of the most common diseases in women of reproductive age. Our aim was to examine whether a twice-weekly thirty-minute exercise intervention could result in a difference in the pulsatility index (PI) of the uterine arteries (UAs) and level of menstrual pain in patients with PD.; Methods: In our prospective observational trial, the observation period included one spontaneous menstrual cycle and the consecutive time of the next menstruation of all participants, aged 18-44, with no extensive sports experience. In total, 73 volunteers were enrolled: 38 persons in the intervention group (IG) and 35 in the control group (CG). The intervention program was accompanied by music, performed in groups under the supervision of a qualified instructor in Hungary. The primary outcome was the difference between the IG and CG regarding the PI values of UAs at the 1st and the 2nd ultrasound (US) Doppler flowmetry. The secondary outcome was the difference between the IG and CG regarding the PI of UAs and menstrual pain measured by using the Numeric Rating Scale and adherence to the intervention. Statistical tests such as an independent-samples t -test, chi-square test, Mann-Whitney test and analysis of covariance (ANCOVA) were used during the analyses.; Results: Examining the mean of the PI of UAs in the IG and the CG at the 1st and the 2nd US measurement, a significant difference was found in the change in the measured value (Z = -2.545; p = 0.011). The IG showed a significantly higher increase in the mean of the PI of UAs (Median = 0.825) than the CG (Median = 0.130). The difference in the PI of the UAs of the IG and the CG is not related to the level of pain in any group ( p = 0.336) and not related to the whole sample ( p = 0.354); furthermore, the level of pain did not significantly differ between the two groups.; Conclusions: Our study is the first to document the significant effects of mild-to-moderate exercise training on the change in the PI of the UAs in individuals with PD. The IG had a reduced blood flow due to circulatory redistribution after exercise. The level of menstrual pain of primary dysmenorrhea patients is independent of the level of blood circulation regarding the PI of the UAs. Randomized controlled studies with more participants and a longer research period are needed to confirm our findings regarding the association between regular exercise and the PI of UAs. The study was registered at clinicaltrials.gov: NCT04618172.

Kovalak Evrim, E., et al. (2022). "Hormonal changes in consecutive clomiphene citrate stimulation cycles and their effect on pregnancy rates." Turkish Journal of Obstetrics and Gynecology 19(3): 221-228.
	Objective: To determine the relationship between the cumulative effect of sequential clomiphene citrate (CC) treatments in unexplained infertile women with intercycle and intracycle serum hormone changes.; Materials and Methods: Patients who received CC 50 mg in the first cycle (group I, n=34) as ovulation induction and those who received CC 50 mg in the second consecutive cycle (group II, n=18) were compared. Basal (cycle days 2-5) and trigger day (the day that recombinant human chorionic gonadotropin is given) levels of gonadotropin and steroid hormones were measured.; Results: The 17OHP increase on trigger day was found to be statistically significantly higher in group II compared to the basal day (p=0.083). The testosterone (T) response on the trigger day of the patients in group II was found to be statistically significantly higher than that in group I (p=0.023). The number of selected follicles was negatively correlated with a follicle-stimulating hormone decrease and positively correlated with an estradiol increase. Endometrial thickness was positively correlated with a luteinizing hormone increase, and cycle cancelation was positively correlated with decreased estradiol.; Conclusion: Based on this study, it was concluded that the reason for the increased efficiency rate in successive cycles of CC may be the cumulative increase in T and 17OHP levels. However, this result was found not to affect the clinical pregnancy rate.; Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors. (©Copyright 2022 by Turkish Society of Obstetrics and Gynecology / Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.)

Kovalak Evrim, E., et al. (2022). "Hormonal Changes in Clomiphene Citrate Cycles in Unexplained Infertility Can Predict Follicle Development?" Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 32(1): 25-32.
	Objectives: To examine the intra-cycle and inter-cycle hormonal changes in the clomiphene citrate (CC) cycle in women with unexplained infertility; and to determine the factors that may predict follicle development or CC failure.; Study Design: Descriptive study.; Place and Duration of Study: This study was conducted at the Bagcilar Training and Research Hospital, Istanbul, Turkey from August 2019 to March 2020.; Methodology: Fifty-two women with unexplained infertility were included. Fifty-two cycles given 50 mg of CC but without follicle development were accepted as Group I. In the next cycle, 48 cycles given 100 mg of CC were accepted as Group II. During every cycle, serum hormone (FSH, LH, E2, P4, A4, DHEA‑S, T, 17‑OHP) levels were measured on days 2, 3, 4 or 5 of the cycle (basal day), and on the days when the leading follicle was triggered (trigger day). Endogenous hormone changes were compared in both the groups with and without follicle development as well as in those who could conceive and those who could not conceive.; Results: Basal day FSH and DHEA‑S values were found to be statistically significantly higher in women with follicle development than those without follicle development (p = 0.02 and p = 0.039, respectively). The trigger day FSH value was found to be significantly lower in women who conceived compared to the basal day value (p = 0.004). The relatively high P4 value (p = 0.008) on the basal day (contingent upon it was not exceeding the 0.5 ng/mL threshold) and the low FSH value (p = 0.015) on the trigger day were found to be statistically significantly different in women who had conceived compared to those who had not.; Conclusion: Basal serum FSH, P4 and DHEA‑S levels can be used as predictors of ovulation in CC cycles in women with unexplained infertility by determining a threshold value with more comprehensive studies to be conducted in the future. Key Words: Androgens, Ovarian stimulation, Clomiphene citrate, Unexplained infertility, Induction of ovulation, Prediction.

Kowalski, J. T., et al. (2021). "A randomized controlled trial of permanent vs absorbable suture for uterosacral ligament suspension." International Urogynecology Journal 32(4): 785-790.
	INTRODUCTION AND HYPOTHESIS: Uterosacral ligament suspension (USLS) is a common procedure for apical pelvic organ prolapse. The procedure has been described using only permanent suture, only absorbable suture and a combination of permanent and absorbable suture. We hypothesized that the use of absorbable suture is not inferior to the use of permanent suture. METHODS: All women undergoing USLS between October 2016 and November 2017 were approached. Subjects were randomized to permanent or absorbable suture. The primary outcome was POP-Q point C 12 months after surgery (non-inferiority limit = 2 cm). A composite outcome of success at 12 months was defined as no apical prolapse ≥ 1/2 TVL, no prolapse beyond the hymen, no prolapse retreatment and no bulge symptoms. RESULTS: Forty-four subjects with mean (SD) age 62.9 (12.0) years and body mass index 29.1 (5.4) kg/m2 were enrolled and underwent USLS. Fifteen (34.1%) had POP-Q stage II and 29 (65.9%) stage III prolapse. Twenty-two were randomized to permanent and 22 to absorbable suture. Forty (90.9%) completed the 12-month follow-up. Median (IQR) POP-Q point C at 12 months was -7 (-10, -6) for the permanent and - 7 (-9, -5.5) for the absorbable suture groups (p = 0.65, non-inferiority p < 0.0002). Four (20%) in the permanent and one (5%) in the absorbable suture group reported bulge symptoms (p = 0.34). Fifteen (75%) in the permanent and 18 (90%) in the absorbable suture groups met criteria for composite success (p = 0.41). Intervention-related adverse outcomes were uncommon and not different between groups. CONCLUSION: Absorbable suture for USLS is not inferior to permanent suture for apical anatomic outcomes.

Kowalski, J. T., et al. (2023). "Impact of Sling at Time of Prolapse Surgery on Overactive Bladder." Urogynecology (Philadelphia, Pa.).
	IMPORTANCE: Prolapse surgery and sling surgery both lead to improvement in overactive bladder. However, less is known regarding how slings performed concurrently with less is know about how overactive bladder symptoms change in patients having prolapse surgery with a sling compared to prolapse surgery without a sling. OBJECTIVE(S): The primary aim was to compare change in postoperative overactive bladder symptoms in patients with preoperative overactive bladder who underwent sling placement versus no sling with prolapse surgery. STUDY DESIGN: This was a secondary analysis of a cohort study evaluating overactive bladder in patients undergoing prolapse surgery. Sling procedures were performed concomitantly for treatment or prevention of stress incontinence. Baseline and 3-month follow-up urinary symptoms were assessed with the Overactive Bladder Questionnaire Short Form (OAB-q SF) and Urinary Distress Inventory-6 (UDI-6). RESULT(S): Of patients with overactive bladder, 26 (40.0%) underwent midurethral sling (MUS) placement and 39 (60.0%) no sling. Preoperative OAB-q SF bother (score [SD], 46.8 [20.2] vs 40.2 [22.1]; P = 0.23) was similar between groups, but UDI-6 scores (59.2 [28.8] vs 43.8 [29.1]; P = 0.04) were higher in the sling group. At 3 months, the change (improvement) in OABq-SF bother (-16.9 [24.1] vs -22.4 [23.0]; P = 0.36), OABq-SF health-related quality of life (22.8 [28.6] vs 22.9 [23.9]; P = 0.99), and UDI-6 (-38.8 [32.9] vs -34.0 [27.8]; P = 0.53) were similar in the MUS and no MUS groups. CONCLUSION(S): Patients with prolapse and overactive bladder undergoing prolapse surgery with a sling had similar improvements in OAB-q SF bother scores compared with those who did not have a sling.Copyright © 2023 American Urogynecologic Society. All rights reserved.

Krämer, B., et al. (2021). "Adhesion prevention after endometriosis surgery - results of a randomized, controlled clinical trial with second-look laparoscopy." Langenbeck's archives of surgery 406(6): 2133-2143.
	PURPOSE: Adhesion formation after endometriosis surgery is a severe problem affecting up to 90% of patients. Possible complications include chronic pain, ileus, and secondary infertility. Therefore, effective adhesion prophylaxis is desirable, for which the adhesion barrier 4DryField® PH is evaluated in the present clinical study. It is a starch-based powder that forms a gel after irrigation with saline solution and thus separates surgical sites as physical barrier for adhesion prevention. METHODS: Fifty patients with extensive and deep infiltrating endometriosis were included in this prospective, randomized, controlled clinical trial with two-staged laparoscopic approach. The patients were randomized into two groups, one receiving 4DryField® PH and the other irrigation with saline solution for adhesion prevention. Adhesion formation was directly scored during second-look interventions considering incidence, extent, and severity. Adhesion prevention treatment in the second surgery was performed corresponding to the first intervention to evaluate the long-term outcome in the later course. RESULTS: Both groups were comparable with respect to relevant patient parameters. Severity and extent of adhesions were significantly reduced by 85% in the 4DryField® PH group compared to the control group (mean total adhesion score 2.2 vs. 14.2; p = 0.004). Incidence of adhesion formation based on the number of affected sites was significantly reduced by 53% in the intervention vs. control group (mean 1.1 vs. 2.3 sites; p = 0.004). Follow-up of secondary endpoints is not yet completed; results will become available at a later stage. CONCLUSION: Adhesion formation could be reduced significantly by 85% by application of the adhesion barrier 4DryField® PH. TRIAL REGISTRATION: Trial registration main ID: DRKS00014720, secondary ID: U1111-1213-4142; date of registration 09th May 2018.

Krämer, B., et al. (2023). "Improvement in Fertility and Pain after Endometriosis Resection and Adhesion Prevention with 4DryField ® PH: Follow-up of a Randomized Controlled Clinical Trial." Journal of Clinical Medicine 12(10).
	Background: Adhesions after endometriosis resection are frequent and the most common causes for chronic pain and secondary infertility. Primary results of our randomized controlled trial (RCT) on adhesion prevention after deep infiltrating endometriosis (DIE) resection using the gel barrier 4DryField ® PH showed 85% adhesion reduction in second-look surgeries. Secondary endpoint data on fertility and pain development were collected during 12-month follow-ups.; Methods: This RCT comprised 50 patients. Preoperatively and after 1, 6 and 12 months, pain scores for cycle-independent pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and dysuria, as well as the number of pregnancies, were recorded,.; Results: The pregnancy rate in the intervention group was significantly higher ( p < 0.05). Pain development was also improved: after 12 months, all 5 subscores were lower in the intervention group and improvements were more pronounced, most prominently concerning cycle-independent pelvic pain and dysmenorrhea, the two subcategories with the highest preoperative scores and, therefore, the highest relevance for the patients. Cycle-independent pelvic pain even recurred in the control group, while barrier application prevented this.; Conclusions: Considering the known causal link between adhesions and pain, it is apparent that the favourable outcomes in the intervention group are linked to effective adhesion prevention. The significant increase in pregnancies is remarkable.

Krasny, S., et al. (2023). "CLINICAL EFFICACY OF PLASMID ENCODING P62/SQSTM1 (ELENAGEN) IN COMBINATION WITH GEMCITABINE IN PATIENTS WITH PLATINUM-RESISTANT OVARIAN CANCER." MedRxiv.
	Purpose: The purpose of this clinical study is to evaluate safety and efficacy of ELENAGEN, a novel anticancer therapeutics (plasmid DNA encoding p62/SQSTM1) protein, as an adjuvant to chemotherapy with Gemcitabin (GEM) in patients with advanced platinum-resistant ovarian cancer. Patients and Methods: This was a prospective randomized multi-center study with two arms. Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks) was administered in both arms: In the Chemo arm (n = 20) GEM was the only treatment, and in the ELENAGEN arm (n = 20) GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1 criteria. Safety was assessed on the basis of adverse events (AEs) and serious AEs (SAEs) according to NCI CTCAE version 5.0. Result(s): To data cut-off, the median follow-up was 13.8 months. There were no SAE -related to ELENAGEN treatment. The median progression-free survival (PFS) was 2.8 and 7.2 mo in Chemo and ELENAGEN arms respectively (p Log-Rank = 0.03). Noteworthy, at the time of cutoff, 9 patients (45%) in Elenagen arm did not progress with the longest PFS recorded so far is 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of Elenagen in the patients with worse prognosis: high pretreatment levels of CA125, progression after only one line of chemotherapy, and peritoneal effusion. Conclusion(s): Addition of ELENAGEN to Gemcitabine is effective in patients with ovarian cancer, including those with a worse prognosis.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Krasny, S., et al. (2024). "Clinical efficacy of plasmid encoding p62/SQSTM1 (Elenagen) in combination with gemcitabine in patients with platinum-resistant ovarian cancer: a randomized controlled trial." Frontiers in Oncology 14: 1343023.
	Background: The purpose of this trial is to evaluate the safety and efficacy of ELENAGEN, a novel anticancer therapeutic DNA plasmid encoding p62/SQSTM1 protein, as an adjuvant to chemotherapy with gemcitabine (GEM) in patients with advanced platinum-resistant ovarian cancer. Method(s): This open-label prospective randomized study with two arms. GEM (1000 mg/m2) on days 1 and 8 every 3 weeks was administered in both arms: in the Chemo arm (n = 20), GEM was the only treatment, and in the ELENAGEN arm (n = 20), GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1, and criteria safety was assessed according to NCI CTCAE version 5.0. Result(s): According to the cutoff data, the median follow-up was 13.8 months. There were no serious adverse events related to ELENAGEN treatment. The median PFS was 2.8 and 7.2 months in the Chemo and ELENAGEN arms, respectively (p Log-Rank = 0.03). Notably, at the time of cutoff, 9 patients (45%) in the ELENAGEN arm did not progress, with the longest PFS recorded thus far being 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of ELENAGEN in patients with worse prognostic factors: high pretreatment levels of CA125 and progression after platinum-free interval <3 months. Conclusion(s): The addition of ELENAGEN to gemcitabine is effective in patients with platinum-resistant ovarian cancer, including those with a worse prognosis. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05979298, identifier NCT05979298, 2023-08-07.Copyright © 2024 Krasny, Baranau, Polyakov, Zharkova, Streltsova, Filimonava, Siarheyeva, Kazlouskaya, Khorau, Gabai and Shneider.

Krause, D. and L. Richardson Debra (2023). "Is there a role for secondary debulking in ovarian cancer? A review of the current literature." Current opinion in obstetrics & gynecology 35(1): 1-5.
	Purpose of Review: Until recently, no data was available from randomized, controlled trials (RCT) to assess the role of secondary cytoreductive surgery (CRS) in the management of recurrent epithelial ovarian cancer. This review highlights results from the three completed RCTs, and other recent literature on this topic.; Recent Findings: Both the AGO and iMODEL criteria predict high rates of complete gross resection at the time of secondary CRS. Overall survival (OS) was improved in the surgical arms in both DESKTOP 3 and SOC-1. In contrast, surgery did not improve OS in GOG 213, but greater than 80% of patients received bevacizumab with chemotherapy in GOG 213.; Summary: Secondary cytoreduction for recurrent ovarian cancer can be considered in patients who meet specific criteria. Available data supports improvement in OS for patients not receiving bevacizumab, who achieve complete gross resection. Surgery is harmful to patients with gross residual disease. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Krawczyk, P., et al. (2022). "Perioperative management of patients with gynecological cancers." Folia medica Cracoviensia 62(4): 25-33.
	Oncological surgery is the primary treatment for gynecological malignancies and is inseparably linked with anesthesia. The modern approach to interdisciplinary and multidisciplinary perioperative care in gynecologic oncological patients improves the outcome. This paper presents a review of perioperative management of patients with gynecologic oncology related to enhanced recovery after surgery and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. We performed a literature search on MEDLINE, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, and Clinical Trials. The database search focused on selected topics related to perioperative gynecological oncology care. The authors also contributed through individual, independent literature searches.

Krawczyk, P., et al. (2022). "Anesthesia for gynecological cancer surgery." Folia medica Cracoviensia 62(3): 19-42.
	Malignant neoplasms are currently a severe medical challenge and the second leading cause of death worldwide. The modern anesthesia applied may improve the patient outcome. This paper presents a review of anesthesia management related to patients with gynaecologic malignancies. It includes the influence of the type of anesthesia on cancer recurrence, application of regional anesthesia in gynaecologic oncologic surgery, and selected aspects of anesthesia for robotic surgery. We performed a literature search on MEDLINE, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, and Clinical Trials. The database search focused on the topics related to anesthesia in gynecological oncology. The authors also contributed through individual, independent literature searches.

Kremer, F., et al. (2023). "Effectiveness of psychosocial interventions for infertile women: A systematic review and meta-analysis with a focus on a method-critical evaluation." PloS One 18(2): e0282065.
	Background: Approximately seven to nine percent of couples of reproductive age do not get pregnant despite regular and unprotected sexual intercourse. Various psychosocial interventions for women and men with fertility disorders are repeatedly found in the literature. The effects of these interventions on outcomes such as anxiety and depression, as well as on the probability of pregnancy, do not currently allow for reliable generalisable statements. This review includes studies published since 2015 performing a method-critical evaluation of the studies. Furthermore, we suggest how interventions could be implemented in the future to improve anxiety, depression, and pregnancy rates.; Method: The project was registered with Prospero (CRD42021242683 13 April 2021). The literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six databases were searched and 479 potential studies were discovered. After reviewing the full texts, ten studies were included for the synthesis. Not all studies reported the three outcomes: four studies each for depression, three for anxiety and nine studies for pregnancy rates were included in the meta-analysis, which was conducted using the Comprehensive meta-analysis (CMA) software.; Results: Psychosocial interventions do not significantly change women's anxiety (Hedges' g -0,006; CI: -0,667 to 0,655; p = 0,985), but they have a significant impact on depression in infertile women (Hedges' g -0,893; CI: -1,644 to -0,145; p = 0,026). Implementations of psychosocial interventions during assisted reproductive technology (ART) treatment do not increase pregnancy rates (odds ratio 1,337; 95% CI 0,983 to 1,820; p = 0,064). The methodological critical evaluation indicates heterogeneous study design and samples. The results of the studies were determined with different methods and make comparability difficult. All these factors do not allow for a uniform conclusion.; Methodological Critical Evaluation: Study design (duration and timing of intervention, type of intervention, type of data collection) and samples (age of women, reason for infertility, duration of infertility) are very heterogeneous. The results of the studies were determined with different methods and make comparability difficult. All these factors do not allow for a uniform conclusion.; Conclusion: In order to be able to better compare psychosocial interventions and their influence on ART treatment and thus also to achieve valid results, a standardised procedure to the mentioned factors is necessary.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Kremer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Krewson, C. (2023). "Mifepristone: a new option for treating adenomyosis?" Contemporary ob/gyn 68(8): 18‐19.
	
Krhut, J., et al. (2023). "Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder." Journal of urology 209(4): 734‐741.
	PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home‐based setting in comparison with standard treatment using solifenacin in treatment‐naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary‐derived variables; Overactive Bladder‐Validated 8‐question Screener, and European Quality of Life‐5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy‐one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment‐related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment‐related adverse events compared to solifenacin and a considerably better benefit‐risk profile.

Krishnan, M., et al. (2021). "Does hysteroscopic resection of uterine septum improve reproductive outcomes: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 303(5): 1131-1142.
	Purpose: Uterine septum in women with subfertility or previous poor reproductive outcomes presents a clinical dilemma. Hysteroscopic septum resection has been previously associated with adverse reproductive outcomes but the evidence remains inconclusive. We aimed to thoroughly and systematically appraise relevant evidence on the impact of hysteroscopically resecting the uterine septum on this cohort of women.; Methods: AMED, BNI, CINAHL, EMBASE, EMCARE, Medline, PsychInfo, PubMed, Cochrane register of controlled trials, Cochrane database of systematic reviews and CINAHL were assessed to April 2020, with no language restriction. Only randomised control trials and comparative studies which evaluated outcomes in women with uterine septum and a history of subfertility and/or poor reproductive outcomes treated by hysteroscopic septum resection against control were included. The primary endpoint was live birth rate, whereas clinical pregnancy, miscarriage, preterm birth and malpresentation rates were secondary outcomes.; Results: Seven studies involving 407 women with hysteroscopic septum resection and 252 with conservative management were included in the meta-analysis. Hysteroscopic septum resection was associated with a lower rate of miscarriage (OR 0.25, 95% CI 0.07-0.88) compared with untreated women. No significant effect was seen on live birth, clinical pregnancy rate or preterm delivery. However, there were fewer malpresentations during labour in the treated group (OR 0.22, 95% CI 0.06-0.73).; Conclusion: Our review found no significant effect of hysteroscopic resection on live birth. However, given the limited evidence available, high-quality randomised controlled trials are recommended before any conclusive clinical guidance can be drawn.

Kristeleit Rebecca, S., et al. (2023). "Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10." British Journal of Cancer 128(2): 255-265.
	Background: Study 10, a four-part Phase 1/2 study, evaluated oral rucaparib monotherapy in patients with advanced solid tumours. Here we report the final efficacy and safety results in heavily pretreated patients with ovarian cancer who received rucaparib in Study 10 Parts 2A and 2B.; Methods: Parts 2A and 2B (Phase 2 portions) enrolled patients with relapsed, high-grade, platinum-sensitive or platinum-resistant, BRCA-mutated ovarian cancer who had received 2-4 (Part 2A) or 3-4 (Part 2B) prior chemotherapies. Patients received oral rucaparib 600 mg twice daily (starting dose). The primary endpoint was the investigator-assessed objective response rate (ORR) by RECIST v1.1.; Results: Fifty-four patients were enrolled: 42 in Part 2A (all had platinum-sensitive disease) and 12 in Part 2B (4 with platinum-sensitive disease; 8 with platinum-resistant disease). ORR was 59.3% (95% CI 45.0-72.4%). The median time to onset of the most common nonhaematological treatment-emergent adverse events (TEAEs) was typically early (<56 days) and was later for haematological TEAEs (53-84 days). The median duration of grade ≥3 TEAEs was ≤13 days.; Conclusions: In patients with relapsed, platinum-sensitive or platinum-resistant germline BRCA-mutant high-grade ovarian cancer who had received ≥2 prior chemotherapies, rucaparib had robust antitumour activity with a safety profile consistent with prior reports.; Clinical Trial Registration: NCT01482715. (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Kristen, M., et al. (2023). "Pelvic Floor Muscle Training for Pelvic Organ Prolapse, Urinary Incontinence, or Fecal Incontinence: A Health Technology Assessment."
	
Kristin, A. and S. Ari (2021). "Progesterone implant in the treatment of endometriosis-related pelvic pain."
	
Kronemyer, B. O. B. (2022). "Ibrexafungerp vs fluconazole for VVC." Contemporary ob/gyn 67(2): 29‐29.
	
Krull, E., et al. (2023). "Assessment of women's sexual quality of life after benign adnexal surgery using vNOTES approach in comparison to conventional laparoscopy: protocol for a randomised controlled trial." BMJ Open 13(9): e073691.
	Introduction Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has already proven its non‐inferiority to conventional abdominal laparoscopy (CAL) for hysterectomy without conversion. The results in terms of efficacy and safety are promising. However, we note a lack of medical literature and no specific randomised controlled trial assessing women's sexual function after vNOTES for benign adnexal surgery. The aim of this RCT is to confirm the non‐inferiority of the vNOTES approach for benign adnexal pathology compared with CAL on women's sexual function. Secondary outcomes will evaluate vNOTES's efficiency, morbidity and postoperative complications compared with CAL for benign adnexal surgery. The relationship between adnexal mass morcellation and the quality of the histological analysis will also be evaluated as secondary outcome. Methods and analysis Women aged 18‐70 years undergoing a benign adnexal surgery at the Geneva University Hospitals will be eligible and randomised with a 1:1 ratio to the CAL arm or the vNOTES arm, if inclusion criteria are met. Participants will complete the Female Sexual Function Index, the Couple Satisfaction Index‐16 and a self‐reported questionnaire on dyspareunia within 4 weeks prior to randomisation and at 3+6 months after surgery. General and clinical data will be collected when the patient is enrolled in the study, during hospitalisation and at 1 month postoperative to assess secondary outcomes. An absence of impairment on sexual function will be confirmed with a stability or an improvement of the evaluated scores in each group at 3 and 6 months postoperative compared with the preoperative scores. We expect to have no statistically significant difference in sexuality questionnaires scores between the two groups. Ethics and dissemination Protocol of this study was validated by the Cantonal Research Ethics Commission of Geneva, Switzerland, on 9 August 2022. We aim to publish the study's results in peer‐reviewed journals within 3 years. Trial registration number NCT05761275.

Kruse, A.-J., et al. (2019). "Vaginal hysterectomy with or without bilateral salpingo-oophorectomy may be an alternative treatment for endometrial cancer patients with medical co-morbidities precluding standard surgical procedures: a systematic review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29(2): 299-304.
	Objective: Vaginal hysterectomy with bilateral salpingo-oophorectomy may be an alternative strategy for patients with low-risk endometrial cancer and medical co-morbidities precluding laparoscopic or abdominal procedures. The current study evaluates the prevalence of co-existent ovarian malignancy in patients with endometrial cancer and the influence of bilateral salpingo-oophorectomy on survival outcomes in these patients.; Methods: Medline and EMBASE were searched for studies published between January 1, 2000 and November 20, 2017 that investigated (1) the prevalence of co-existing ovarian malignancy (either metastases or primary synchronous ovarian cancer in women with endometrial cancer, and (2) the influence of bilateral salpingo-oophorectomy on recurrence and/or survival rates.; Results: Of the pre-menopausal and post-menopausal patients (n=6059), 373 were identified with metastases and 106 were identified with primary synchronous ovarian cancer. Of the post-menopausal patients (n=6016), 362 were identified with metastases and 44 were identified with primary synchronous ovarian cancer. Survival outcomes did not differ for pre-menopausal patients with endometrial cancer with and without bilateral salpingo-oophorectomy (5-year overall survival rates were 89-94.5% and 86-97.8%, respectively).; Conclusion: Bilateral salpingo-oophorectomy during vaginal hysterectomy seems to have a limited impact on disease outcome in patients with endometrial cancer. These results support the view that vaginal hysterectomy alone or with bilateral salpingo-oophorectomy may be an option for patients with endometrial cancer who are not ideal surgical candidates.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Krutova, V. A. and A. K. Golovko (2021). "OVARIAN STIMULATION IN THE LUTEIN PHASE OF THE MENSTRUAL CYCLE AND IN THE DOUBLE STIMULATION MODE IN PATIENTS WITH LOWER OVARIAN RESERVE VALUES." Akusherstvo i Ginekologiya (Russian Federation)(12): 24-30.
	In vitro fertilization is still characterized by lower success rates in women who fail to respond adequately to controlled ovarian stimulation, also known as poor responders. To search for an effective treatment for this group of patients is an important problem. Objective(s): To provide up-to-date information on the use of protocols for ovarian function stimulation in the luteal phase of the menstrual cycle and in the double stimulation mode in patients with lower ovarian reserve values. Method(s): Publications were sought for in the databases PubMed, eLibrary, Web of Science, Cochrane Library, and CyberLeninka. The search depth was 10 years. The systematic search used the following keywords: ovarian stimulation in the luteal phase, double stimulation, and diminished ovarian reserve; as well as double stimulations, luteal-phase ovarian stimulation, poor ovarian response, controlled ovarian stimulation, and second follicular wave in English-language publications. Result(s): The review included 42 of the 89 literature sources analyzed. This review of current studies has shown that ovarian stimulation can be safely and effectively initiated at any point in the menstrual cycle. Double ovarian stimulation is a promising protocol for patients, from whom the largest number of oocytes should be retrieved in the shortest possible time when one superovulation stimulation session is not enough or when the period for assisted reproductive technologies is limited. The literature data indicate that this strategy is a possible option to compensate for the inadequate ovarian response that sometimes occurs in assisted reproductive technology programs, especially in patients with lower ovarian reserve values. Conclusion(s): Ovarian function stimulation in the follicular and luteal phases of the menstrual cycle is a new strategy aimed at increasing the numbers of retrieved oocytes and obtained good-quality embryos. Just the same, there is a need for further investigation of the efficiency and safety of double stimulation in patients with diminished ovarian reserve.Copyright © A group of authors, 2021.

Krychman, M., et al. (2023). "A Randomized Trial on the Effectiveness of Five Water-Based Personal Lubricants in Premenopausal and Postmenopausal Women."  141(5): 90S‐91S.
	INTRODUCTION: Vaginal dryness is generally associated with postmenopausal women; however, it may occur at all ages. Personal lubricants can relieve discomfort associated with vaginal dryness, although clinical data supporting the efficacy of many lubricants are limited. METHODS: An open‐label, parallel‐design study was performed in heterosexual women in monogamous relationships, aged 18‐65 years with mild‐to‐moderate vaginal dryness and dyspareunia. The study population (n5174) included an approximate 50:50 ratio of premeno‐pausal to postmenopausal women. The randomization schedule was stratified by menopausal status. Participants were randomized to use one of five water‐based lubricants and instructed to use their lubricant during vaginal intercourse at least once a week over a 4‐week period. The Female Sexual Function Index (FSFI) measured sexual functioning after 4 weeks of use as an indicator of lubricant performance. The total FSFI comprises six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain reduction. A greater than 4‐point increase in total FSFI is considered clinically important. RESULTS: An increase in FSFI total score of greater than 4 points was found for all lubricants in the total population and for four of five lubricants in the premenopausal subgroup, as indicated by the mean differences to baseline. The number of participants in sexual function (total FSFI.26.55) after treatment was significantly greater than the number in sexual function before treatment for both subgroups (premenopausal, 19.3‐78.4%; post‐menopausal, 22.3‐75.3%; P,.0001 for both). CONCLUSION: These lubricants can be used not only to relieve symptomatology of vaginal dryness and dyspareunia, but to enhance overall sexual satisfaction regardless of menopausal status.

Krychman, M., et al. (2024). "Drospirenone 4mg use in 44 premenopausal women ages 40 - 51 and its influence on bleeding patterns: Results from a phase III clinical trial." Journal of Neurosurgical Anesthesiology 36(1): 1284.
	Objective: Contraception is an essential aspect of caring for peri-menopausal women not desiring pregnancy. We performed a sub-analysis of 44 participants >=40 years enrolled in a phase III clinical trial to evaluate the efficacy, safety, and bleeding patterns while using drospirenone 4mg as an oral contraceptive. Design(s): To be eligible for enrollment, individuals were required to have regular menstrual cycles in the past six months (unless pregnant, breastfeeding, or using hormonal contraception). Participant demographics (including age, substance use, and risk factors for thromboembolism) were collected during study enrollment. A daily e-diary recorded bleeding, medication use, and sexual activity. Adverse event monitoring was conducted via self-report at all study visits. Data were analyzed using SAS and Excel. Result(s): Of the 44 premenopausal women ages >=40, 13 participants (30%) had a BMI >=30 kg/m2. No participants reported a family history of VTE or a medical disorder pre-disposing them to VTE. All participants were considered to have at least one risk factor of VTE due to age. Six participants (13.6%) were current nicotine users, 8 participants (18.1%) were former nicotine users, and 30 (68.2%) denied previous nicotine use. Moderate alcohol use was reported by 25 participants (56.8%), while the remaining 19 participants (43.2%) abstained from alcohol use. Five participants discontinued the clinical trial prematurely due to adverse events: one for a macular/ papular rash; two participants discontinued the trial due to breakthrough bleeding; one participant discontinued due to mood swings and breakthrough bleeding; and one participant discontinued due to abdominal pain. There was a general trend towards less bleeding and spotting days with continued use. Reported bleeding days, spotting days, and total bleeding and spotting days are presented in Table 1. Contraceptive efficacy was not evaluated in this population. However, no pregnancies occurred in this subpopulation. The FDA assigned Pearl Index in participants <=35 years old is 4.0. In this trial, no cases of hyperkalemia occurred in participants >=40 years old; two participants <40 years old discontinued drospirenone 4mg due to persistent hyperkalemia. There were no thromboembolic events or cardiovascular events throughout the clinical development program. Conclusion(s): Most participants ages 40 - 51 had a bleeding change while enrolled in this clinical trial. Further research is needed to determine the long-term safety profile, tolerability profile, and bleeding changes during 4mg drospirenone use in this sub-population.

Krychman, M., et al. (2023). "A Randomized Trial on the Sexual Effectiveness and Impact on the Vaginal Microbiome of Reformulated Personal Water Lubricants with Lowered Osmolality and pH in Premenopausal and Postmenopausal Women."  20.
	Introduction Vaginal dryness may be associated with postmenopausal women; however, it may also occur due to chronic medical conditions and as a direct side effect from medications. Personal lubricants can address sexual complaints and symptomatology associated with vaginal dryness, although clinically published data supporting their efficacy remains limited. Age‐associated vaginal‐physiological changes due to hypoestrogenic milieux include increased pH, decreased natural lubrication, reduced endothelial rugae and altered vaginal microbiome. While personal lubricants may alleviate symptoms, their definitive effects on the vaginal microbiome remain understudied and underappreciated. Objective This study examined reformulated water‐based lubricants (lowered osmolalities and pH,) and their effect on female sexual function compared to their counterparts (higher osmolalities/increased pH). A secondary analysis examined if these reformulated lubricants influenced the vaginal microbiome of women from different age groups. Methods An open‐label, parallel‐design study was performed in heterosexual women in stable monogamous relationships, aged 18‐65 years with mild‐to‐moderate vaginal dryness and dyspareunia. The study population (n=174) included an approximate 50:50 ratio of premenopausal to postmenopausal women. The randomization schedule was stratified by menopausal status. Subjects were randomized to use one of five water‐based lubricants and instructed to use their lubricant during vaginal intercourse at least once a week over a 4‐week period. The Female Sexual Function Index (FSFI) measured sexual functioning after 4 weeks of use as an indicator of lubricant performance. More than a 4‐point increase in total FSFI is deemed clinically important. From the study‐enrolled subjects, 50 females were randomized to one of five lubricant treatment groups for secondary microbiome analysis. To this end, four vaginal swabs per participant were sampled during pre‐ (“baseline”) and post‐ (“2 hours”, “24 hours” and “4 weeks”) lubricant application to assess bacterial diversity via 16S sequencing. Additionally, vaginal moisture and pH measurements were collected at baseline, 2 hours, and 24 hours postlubricant application and correlated with microbiome diversity and richness using non‐parametric tests and linear mixed models. Results An increase in FSFI total score of >4 points was found for all lubricants in the total population and for 4/5 lubricants in the premenopausal subgroup, as indicated by the mean differences to baseline. The number of subjects in sexual function (total FSFI >26.55) after treatment was significantly greater than the number in sexual function before treatment for both subgroups (premenopausal 19.3% to 78.4%; postmenopausal 22.3% to 75.3%; p<0.0001 for both). Lactobacillus species and Gardnerella vaginalis were the predominant taxa across all participants. Repeated lubricant applications did not alter the vaginal microbiome for up to 4 weeks post‐product applications. Microbial diversity and relative abundance differed significantly between age groups but remained unaffected during product applications. Relative abundance of Lactobacilli spp. negatively correlated with vaginal pH while that of Gardnerella spp. showed a positive correlation with vaginal pH across all age groups. Conclusions These reformulated lubricants can be used not only to relieve symptomatology of vaginal dryness and dyspareunia, but to enhance overall sexual satisfaction regardless of menopausal status. These study lubricants demonstrated no significant impact on vaginal microbiome. Further studies with larger samples are warranted.

Krzysztof, K. U. S., et al. (2023). "POLYCYSTIC OVARY SYNDROME (PCOS) - THE APPLICATION OF SELECTED OFF-LABEL DRUGS FOUND IN MEDICAL DATABASES." Acta Poloniae Pharmaceutica - Drug Research 80(5): 695-703.
	Medical databases are crucial tools in medicine and pharmacy, aiding studies on the impact of medical products on health and informing treatment decisions. However, prescribers must blend database insights with clinical expertise for accurate choices. Clinical experience doesn't always align with drug Summaries of Product Characteristics (SPCs). While SPC guidelines ensure safety, they might not optimize efficacy. For instance, treating polycystic ovary syndrome (PCOS) often benefits from off-label therapies that are clinically and cost-effective. The study aimed to identify potential PCOS treatments beyond approved uses in Poland and globally. The methodology involved reviewing databases used by medical professionals. Out of 29, 11 databases were chosen based on off-label drug availability and relevance to PCOS. Results show that medical databases aid medical professionals in finding off-label PCOS treatments. These databases also assess a drug's potential efficacy and risks. However, their usefulness has limits, lacking comprehensive data on usage, mechanisms, and safety. When using literary databases, keyword selection significantly influences search results.Copyright © 2023 by Polish Pharmaceutical Society. This is an open-access article under the CC BY NC license (https://creativecommons.org/licenses/by-nc/4.0/).

Krzyzanowski, J., et al. (2022). "Minimally invasive treatment options for uterine fibroids - state-of-the art 2021." Ginekologia polska 93(3): 242-247.
	Objectives: Uterine leyomyomas are benign, monoclonal tumors that can cause abnormal uterine bleeding, pelvic pain, dyspareunia and/or obstruction of bladder or rectum. Women's growing interest in treatments that avoid surgery and/or preserve the uterus has contributed to the development of minimally invasive methods. Conducting a literature review and assessment of the effectiveness and safety of minimally invasive methods of treating fibroids, with particular emphasis on high intensity focused ultrasound.; Material and Methods: Systematic review of MEDLINE, Cochrane and PubMed was performed using the following key words: uterine artery embolization, high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, minimally invasive, leiomyoma, fertility, pregnancy. English abstracts relevant to the topic were selected. Full-text articles were carefully analyzed.; Results: Uterine artery embolization is a proven, widely accepted method that is effective in appropriately qualified cases. Although high focused ultrasound is still an experimental procedure, preliminary studies seem to be promising. If its efficacy and safety are confirmed in randomized controlled trials, this method may find its place in clinical practice. Microwave and radiofrequency ablation are interesting minimally invasive methods with the future potential to be recognized as a method of treating fibroids.; Conclusions: Minimally invasive methods are becoming an important treatment option for fibroids. Further research is needed to recognize these procedures as a fully-fledged alternative to surgical treatment.

Kuan-Yin, L. and D. Ph (2023). "The Feasibility and Effects of a Telehealth-delivered Physical Therapy Program for Postmenopausal Women With Urinary Incontinence." ClinicalTrials.gov.
	This is a non-inferiority randomized controlled trial with a nested cross-sectional study and a nested qualitative interview study. Sixty community-dwelling postmenopausal women with urinary incontinence, aged \>40 years, will be recruited and randomly allocated to two groups, telehealth group or face-to-face group. All groups will receive a 12-week pelvic floor muscle training. The face-to-face group will be supervised by a female physical therapist who will provide pelvic floor muscle training twice a week. The training will be adjusted according to the performance of the participant. The telehealth group will receive eight sessions of individualized pelvic floor muscle training provided by a physical therapist via telehealth in addition to a weekly telephone coaching. The baseline, post-intervention, and 3-month follow-up assessments will include feasibility outcomes, measurements of anthropometry, body composition (body composition monitor), hand grip strength (dynamometer), functional exercise capacity (six minute walk test), and pelvic floor muscle function (vaginal manometry, transperineal ultrasound and digital palpation) and two questionnaires about symptom severity of urinary incontinence and physical activity levels. This study will provide evidence of effectiveness of different delivery modes of physical therapy program for postmenopausal women with urinary incontinence and health-care professionals working with this population in clinical practice.

Kucukkaya, B. and S. Kahyaoglu (2021). "Effectiveness of pelvic floor muscle and abdominal training in women with stress urinary incontinence." Psychology, health & medicine 26(6): 779-786.
	The aim of this study was to investigate the effectiveness of pelvic floor muscle training and abdominal training in women with stress urinary incontinence. The study included 64 female patients (aged 18 to 49 years) with stress urinary incontinence. Patients were randomly allocated into the pelvic floor muscle training (PFMT) or pelvic floor muscle plus abdominal training (PFMT+AT) groups. Clinical data included stress test results, pelvic floor activity measurements, and Urinary Distress Inventory, and Incontinence Impact Questionnaire responses. The increase in the pelvic floor muscle activity (from the 0th to the 4th week, from the 4th to the 8th week, and from the 0th to the 8th week) was significantly greater for the PFMT+AT group than for the PFMT group (p < 0.05). The negativity rate of the stress test at the 4th week was significantly higher for the PFMT+AT group (93.7%) than for the PFMT group (53.1%) (p < 0.001). Women with stress urinary incontinence benefit more from pelvic floor muscle training plus abdominal training than from pelvic floor muscle training alone in terms of increasing their pelvic floor muscle activity and quality of life, and they also experience an earlier recovery.

Kulhan, M., et al. (2023). "Effect of lymph node sampling type on oncologic outcomes in endometrial cancers: comprehensive pelvic and paraaortic lymphadenectomy vs. sentinel lymph node mapping with indocyanine green." European Review for Medical and Pharmacological Sciences 27(7): 3096-3104.
	Objective: Sentinel lymph node biopsy refers to an innovative and minimalist surgical approach that has been introduced to reduce both complications and morbidity. A definitive answer to the question of whether lymphadenectomy is performed for staging or curative purposes in endometrial cancer has not yet been found. The aim of this study is to compare patients who underwent sentinel lymph node biopsy with indocyanine green and those who underwent laparoscopic complete surgical staging in terms of survival.; Patients and Methods: A total of 182 patients was included in the study. The patients were divided into two groups according to the lymph node sample type. The two groups were compared in terms of oncological outcomes.; Results: 92 patients underwent sentinel lymph node mapping (SLNM cohort) and 90 patients underwent extensive pelvic and paraaortic lymphadenectomy (SCL cohort). Considering only patients with negative lymph nodes, the Sentinel cohort was associated with a reduced DFS and OS (p=0.008 and p=0.005, respectively). This difference may be due to the longer follow-up times of patients with comprehensive lymph node sampling. On the other hand, There was no difference in survival in lymph node positive cases.; Conclusions: Sentinel lymph node dissection has no negative effect on survival in lymph node positive patients.

Kulkarni, M., et al. (2022). "Outcomes following sacrocolpopexy using ultralight and lightweight mesh." International Urogynecology Journal 33(9): 2475-2483.
	Introduction and Hypothesis: This study reports the long-term anatomic and subjective outcomes following sacrocolpopexy based on mesh weight and provides device-specific data.; Methods: This cohort study compared ultra-lightweight (≤ 20 g/m 2 ) with lightweight mesh (≥ 25 g/m 2 ). The primary outcome was composite failure defined as at least one of ≥ stage 2 apical prolapse, anterior or posterior vaginal wall beyond hymen, complaint of bulge or retreatment. Effect measure estimates were calculated as the incidence rate ratio of composite failure comparing the use of ultra-light with lightweight mesh. Crude and adjusted incidence rate ratios (IRRs) were obtained using uni- and multivariable Poisson regression models.; Results: Of 358 women who met inclusion criteria, 220 (61%) agreed to attend for review; 95 (43%) had ultra-lightweight mesh and 125 (57%) had lightweight mesh including Upsylon TM . Median follow-up for ultra-light and lightweight mesh was 36 (IQR 22-42) and 63 (IQR 48-87) months, respectively (p < 0.001). Accounting for differences in follow-up time, there was no significant difference in composite failure between ultra-light and lightweight mesh groups (IRR 1.47, 95% CI 0.83-2.52, p = 0.15). This persisted after adjustment for age, body mass index, parity, smoking and presence of advanced prolapse prior to surgery (IRR 1.52, 95% CI 0.94-2.47, p = 0.087). Mesh exposure for both groups was mostly asymptomatic, and the rate was 7% for the ultra-light group and 8% in the lightweight group. Overall, repeat surgery for recurrent apical prolapse and mesh exposure occurred in 4% and 2%, respectively.; Conclusions: Ultra-lightweight mesh appears to have similar incidence rate of failure compared to lightweight mesh. Upsylon TM mesh has a similar low rate of recurrent apical prolapse and mesh exposure. (© 2022. The International Urogynecological Association.)

Kulkarni, S., et al. (2023). "Polycystic ovary syndrome: Current scenario and future insights." Drug discovery today 28(12): 103821.
	Polycystic ovary syndrome (PCOS) prevails in approximately 33% of females of reproductive age globally. Although the root cause of the disease is unknown, attempts are made to clinically manage the disturbed hormone levels and symptoms arising due to hyperandrogenism, a hallmark of PCOS. This review presents detailed insights on the etiology, risk factors, current treatment strategies, and challenges therein. Medicinal agents currently in clinical trials and those in the development pipeline are emphasized. The significance of the inclusion of herbal supplements in PCOS and the benefits of improved lifestyle are also explained. Last, emerging therapeutic targets for treating PCOS are elaborated. The present review will assist the research fraternity working in the concerned domain to access significant knowledge associated with PCOS. (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Kumar, A., et al. (2022). "Curcumin: The Golden Nutraceutical on the Road to Cancer Prevention and Therapeutics. A Clinical Perspective." Critical Reviews in Oncogenesis 27(3): 33-63.
	Cancer is considered as the major public health scourge of the 21st century. Although remarkable strides were made for developing targeted therapeutics, these therapies suffer from lack of efficacy, high cost, and debilitating side effects. Therefore, the search for safe, highly efficacious, and affordable therapies is paramount for establishing a treatment regimen for this deadly disease. Curcumin, a known natural, bioactive, polyphenol compound from the spice turmeric (Curcuma longa), has been well documented for its wide range of pharmacological and biological activities. A plethora of literature indicates its potency as an anti-inflammatory and anti-cancer agent. Curcumin exhibits anti-neoplas-tic attributes via regulating a wide array of biological cascades involved in mutagenesis, proliferation, apoptosis, onco-gene expression, tumorigenesis, and metastasis. Curcumin has shown a wide range of pleiotropic anti-proliferative effect in multiple cancers and is a known inhibitor of varied oncogenic elements, including nuclear factor kappa B (NF-kappaB), c-myc, cyclin D1, Bcl-2, VEGF, COX-2, NOS, tumor necrosis factor alpha (TNF-alpha), interleukins, and MMP-9. Further, curcumin targets different growth factor receptors and cell adhesion molecules involved in tumor growth and progres-sion, making it a most promising nutraceutical for cancer therapy. To date, curcumin-based therapeutics have completed more than 50 clinical trials for cancer. Although creative experimentation is still elucidating the immense potential of curcumin, systematic validation by proper randomized clinical trials warrant its transition from lab to bedside. Therefore, this review summarizes the outcome of diverse clinical trials of curcumin in various cancer types.Copyright © 2022 by Begell House, Inc. www.begellhouse.com.

Kumar, D. and Chandersheikhar (2023). "ORAL DYDROGESTERONE AND MICRONIZED PROGESTERONE IN THREATENED ABORTION." International journal of academic medicine and pharmacy 5(1): 14‐16.
	Background: To compare oral dydrogesterone and micronized progesterone in threatened miscarriage. Materials and Methods: Eighty‐ four patients with pain or bleeding per vaginum were randomized into two groups of 45 each. Group I patients received 10 mg oral dydrogesterone twice daily and in group II 200 mg oral micronized progesterone twice daily. Parameters such as pain and bleeding per vaginum, spontaneous abortion, preterm delivery, full term delivery, IUGR, mode of delivery and birth weight of new born at the time of delivery were noted. Result: Age group 18‐24 years comprises of 18 patients in group I and 20 in group II, 25‐31 years had 20 in group I and 17 in group II and 32‐38 years had 7 in group I and 8 in group II. Normal weight babies were 8 in group I and 15 in group II and growth restricted babies were 37 in group I and 30 in group II. Mode of delivery was cesarean in 5 in group I and 8 in group II and vaginal in 40 in group I and 37 in group II. The birth weight of the baby at 6 weeks‐ 8 weeks in group I was 2.7 kgs and in group II was 2.4 kgs, at 8 weeks‐10 weeks was 2.7 kgs in group I and 2.5 kgs in group II and 10 weeks‐12 weeks was 2.5 kgs in group I and 2.3 kgs in group II. The difference was significant (P< 0.05). Full term babies were 35 in group I and 36 in group II, pre‐ term 5 in group I and 4 in group II and abortion 5 in group I and 5 in group II. The difference was significant (P> 0.05). Conclusion: Dydrogesterone was efficient in reducing pain in lower abdomen and bleeding per vaginum as compared to micronized progesterone.

Kumar, D., et al. (2023). "Comparing the effectiveness of mother-focused interventions to that of mother-child focused interventions in improving maternal postpartum depression outcomes: A systematic review." PloS One 18(12): e0295955.
	Background: Most empirically researched interventions for postpartum depression (PPD) tend to target mothers' depression alone. Harmful effects of PPD on physical and mental health of both mother and child has led researchers to investigate the impact of interventions on PPD and child outcomes together. So far, the evidence is limited regarding how these interventions compare with those focusing only on mothers' depression. This review compares the effectiveness of PPD-improving interventions focusing only on mothers with those focusing on mother and child together.; Methods: Nine electronic databases were searched. Thirty-seven studies evaluating mother-focused (n = 30) and mother-child focused interventions (n = 7) were included. Under each category, three theoretical approaches-psychological, psychosocial and mixed-were compared using standardized qualitative procedures. The review's primary outcome was maternal PPD.; Results: A higher proportion of mother-focussed interventions [20/30 (66.7%)] brought significant reduction in PPD outcomes as compared to a lower proportion of mother-child focused interventions [4/7 (57.14%)]. Mother-focused mixed approaches [3/3 (100%)] performed better in improving PPD than psychological [16/24 (67%)] or psychosocial approaches [1/3 (33.3%)] alone. Amongst mother-child focused interventions, psychosocial approaches performed well with two-thirds demonstrating positive effects on PPD.; Conclusion: The evidence strongly favors mother-focused interventions for improving PPD with mixed interventions being more effective. Psychosocial approaches performed better with PPD once child-related elements were added, and also seemed best for child outcomes. Psychological approaches were most practiced and effective for PPD, irrespective of the intervention's focus. Further trials are needed to unpack intervention components that improve PPD and increase uptake, especially in lower-and middle-income countries.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Kumar, P., et al. (2023). "Gefitinib: An Updated Review of its Role in the Cancer Management, its Nanotechnological Interventions, Recent Patents and Clinical Trials." Recent patents on anti-cancer drug discovery 18(4): 448-469.
	Background: Gefitinib, a tyrosine kinase inhibitor, is effectively used in the targeted treatment of malignant conditions. It suppresses the signal transduction cascades leading to cell proliferation in the tumors and is now currently approved in several countries globally as secondline and third-line treatment for non-small cell lung cancer (NSCLC).; Objective: This review is aimed to summarize the journey of gefitinib as an established anticancer drug for the management of various cancers. Moreover, this review will focus on the mechanism of action, established anticancer activities, combination therapy, nanoformulations, as well as recent clinical trials and patents on gefitinib.; Methods: The data for this review was collected from scientific databases such as PubMed, Science Direct, Google Scholar, etc. Recent patents on gefitinib granted in the last two years were collected from databases Patentscope, USPTO, Espacenet, InPASS and Google Patents. Data for the recent clinical trials were obtained from the U.S. National Library of Medicine database.; Results: Recent pre-clinical and clinical studies during the period 2015-2021 demonstrating the efficacy of gefitinib were selected and summarized. Total 31 patents were granted in the year 2020-2021 concerning gefitinib. The efficacy of gefitinib against lung cancer, as well as other cancer types, including breast, prostate, colon, cervix etc., was reviewed.; Conclusion: Gefitinib showed significant advantages in being more effective, safer and more stable, and the associated biopharmaceutical problems are addressed by the application of nanotechnology. The combination therapy using gefitinib and various anticancer molecules of natural and synthetic origin has shown an improved anticancer profile. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Kumar, P., et al. (2021). "Intralipid therapy and adverse reproductive outcome: is there any evidence?" Reproduction & fertility 2(3): 173-186.
	Controversy exists regarding the benefits of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis were performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR): 2.97, 2.05-4.29), pregnancy rate (OR: 1.64, 1.31-2.04), and LBR (OR: 2.36, 1.75-3.17), with a reduction in MR (OR: 0.2, 0.14-0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.; Lay Summary: There is controversy regarding the benefits and efficacy of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no credible evidence to support their use. A situation we frequently face as medical professionals is patients asking us to consider immune therapy (such as intralipid) for reproductive failure where good quality embryos have been used. Intralipid infusions have been reported to improve pregnancy rates with IVF, and reduce the miscarriage risk in selected patient groups, but study results are not universally accepted. We have performed a detailed review and analysis of the literature to determine if there is any benefit to this immune treatment in specific patient groups. Our paper identified and analyzed 12 studies, finding that treatment with intravenous intralipid leads to an improvement in implantation, pregnancy and live birth rates, with a decrease in miscarriage rate. This study shows that there is evidence to suggest consideration of intralipid in certain patients where standard treatments have failed. (© The authors.)

Kundarti, F. I., et al. (2023). "Mindfulness improves the mental health of infertile women: A systematic review." Journal of public health research 12(3): 22799036231196693.
	Infertility in women causes mental health problems, the bad ones. Women with infertility need psychological treatment using mindfulness interventions. This study's purpose was to analyze mindfulness's effect on the mental health of women with infertility through a systematic review. The method used in this systematic review was by searching through the following databases; ProQuest database, Wiley Library, Pubmed, Scopus, Science Direct, Sage Journal, Cochrane Library, and Cambridge Core from January 2011 to December 2021. Nine articles met the inclusion criteria. Results show that the use of mindfulness was found to be effective in reducing mental disorders in women with infertility. Nine articles that meet the criteria for inclusion. According to a study on the effects of mindfulness on infertile women, affect increasing mental health levels by reducing mental health disorder scores. Mindfulness has been proven to be an effective intervention for women undergoing infertility-related mental disorders such as stress, anxiety, and depression. However, different types of mindfulness-based interventions are used to target different mental health issues. For example, Mindfulness-Based Stress Reduction (MBSR) targets stress and anxiety while Mindfulness-Based Cognitive Therapy (MBCT) targets depression. Additionally, specific mindfulness for example, for the midwifery profession can be developed to improve the quality and treatment outcomes of healthcare for women struggling with infertility problems.

Kuniyoshi, H., et al. (2021). "Comparison of the analgesic effects continuous epidural anesthesia and continuous rectus sheath block in patients undergoing gynecological cancer surgery: a non-inferiority randomized control trial." Journal of anesthesia 35(5): 663-670.
	PURPOSE: We investigated the non-inferiority of continuous rectus sheath block to continuous epidural anesthesia for postoperative analgesia of gynecological cancer patients. METHODS: One hundred ASA-PS 1-2 patients via a median incision up to 5 cm above the navel were randomized into a continuous epidural anesthesia (CEA) group and a continuous rectus sheath block (CRSB) group. Following surgery, they have controlled with intravenous patient-controlled analgesia (IV-PCA) as basal postoperative analgesia. For patients in the CEA group were administered 0.25% levobupivacaine at 5 mg/h. Patients in the CRSB group, catheters were inserted on both sides of the posterior rectus sheath after surgery. They received 0.25% levobupivacaine on both sides at 7.5 mg/h. To determine whether CRSB is non-inferior to CEA in postoperative treatment, pain at rest and movement was assessed using the Numerical Rating Scale (NRS). The non-inferiority margin of NRS difference between CRSB and CEA was set at 1.3 difference in means. The primary outcome was non-inferiority comparisons of NRS at rest/at movement after surgery, while the secondary outcome included the frequency of requesting IV-PCA and rescue drugs. RESULTS: NRS at rest in the CRSB group was not inferior to that in the CEA group. On the other hand, the NRS at movement at 4, 6, 8, 12 h following surgery in the CRSB group was inferior to CEA. There was no difference in the frequency of requesting IV-PCA and rescue drugs. CONCLUSIONS: CRSB showed the non-inferiority to CEA for postoperative analgesia at rest, while CRSB was not non-inferior to CEA at movement in gynecological cancer patients. CRSB would be a substitute when CEA is contraindicated as a component of postoperative multimodal analgesia.

Kuon, R. J. and K. Vomstein (2022). "Relevance of chronic endometritis in recurrent implantation failure and recurrent miscarriage." Gynakologische Endokrinologie 20(4): 244-251.
	Background: Due to causes which frequently cannot be identified, recurrent implantation failure and recurrent miscarriages are frustrating situations for both patients and treating physicians. In addition to embryonic factors, endometrial causes are discussed as potential risk factors, with chronic endometritis (CE) coming into the focus of scientific interest in recent years. Objective(s): This article aims to provide an overview of the clinical symptoms, pathophysiology, diagnostics and potential treatment options of CE in recurrent implantation failure and recurrent miscarriage. Result(s): Studies indicate that CE has negative effects on implantation and development in (early) pregnancy via various mechanisms (including an impact on cytokine secretion and alterations in the composition of lymphocyte subpopulations in the endometrium). The immunohistochemical detection of CD138-positive plasma cells in endometrial biopsies has been established as the gold standard for the diagnostics of CE; however, there is still no consensus on the exact diagnostic criteria causing high variations in the reported prevalence of CE in these patient groups of about 10-50%. Successful treatment is achieved with antibiotics, as evidenced both histologically by plasma cell clearance and clinically by higher implantation, pregnancy and live birth rates. Conclusion(s): Data on the diagnostics and treatment of CE in patients with recurrent implantation failure and recurrent miscarriage are promising. The determination of exact diagnostic criteria and the treatment of patients with a persistence of CE despite antibiotic treatment are particularly challenging. Further randomized, ideally placebo-controlled, prospective studies with adequate case numbers are needed to provide results in the coming years, so that the value of CE can be further strengthened.Copyright © 2022, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Kuon, R. J. and K. Vomstein (2022). "Role of natural killer cells in early pregnancy." Gynakologie 55(9): 621-630.
	Background: Natural killer (NK) cells play a pivotal role in the establishment of a successful pregnancy. They are found in peripheral blood (peripheral NK cells) as well as in the endometrium and decidua (uterine NK cells). Objective(s): This article aims to provide an overview of the origin, function, and diagnostics of NK cells, as well as to highlight possible therapeutic options. Result(s): Different types of NK cells differ significantly in their cytotoxicity. About 90% of uterine NK cells show low cytotoxicity with high cytokine production, whereas peripheral NK cells show high cytotoxicity and low cytokine production. Elevated uterine and peripheral NK cells are associated with miscarriage, hypertension, preeclampsia, and fetal growth restriction. Conclusion(s): A detailed understanding of the various mechanisms of implantation and (early) pregnancy is paramount to improving the success rates of reproductive interventions, as well as to prevent pregnancy complications. There is a growing number of studies on immunomodulatory therapies for NK cell changes investigating, e.g., corticosteroids, lipid infusions, and immunoglobulins. However, the studies are heterogeneous in design, methodology, intervention, and study population, which makes not only comparison and interpretation difficult, but also the development of evidence-based therapeutic strategies.Copyright © 2022, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Kurnit Katherine, C. and M. Frumovitz (2022). "Primary mucinous ovarian cancer: options for surgery and chemotherapy." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Primary mucinous ovarian cancer is a rare type of epithelial ovarian cancer. In this comprehensive review we discuss management recommendations for the treatment of mucinous ovarian cancer. Although most tumors are stage I at diagnosis, 15-20% are advanced stage at diagnosis. Traditionally, patients with primary mucinous ovarian cancer have been treated similarly to those with the more common serous ovarian cancer. However, recent studies have shown that mucinous ovarian cancer is very different from other types of epithelial ovarian cancer. Primary mucinous ovarian cancer is less likely to spread to lymph nodes or the upper abdomen and more likely to affect younger women, who may desire fertility-sparing therapies. Surgical management of mucinous ovarian cancer mirrors surgical management of other types of epithelial ovarian cancer and includes a bilateral salpingo-oophorectomy and total hysterectomy. When staging is indicated, it should include pelvic washing, omentectomy, and peritoneal biopsies; lymph node evaluation should be considered in patients with infiltrative tumors. The appendix should be routinely evaluated intra-operatively, but an appendectomy may be omitted if the appendix appears grossly normal. Fertility preservation can be considered in patients with gross disease confined to one ovary and a normal-appearing contralateral ovary. Patients with recurrent platinum-sensitive disease whose disease distribution suggests a high likelihood of complete gross resection may be candidates for secondary debulking. Primary mucinous ovarian cancer seems to be resistant to standard platinum-and-taxane regimens used frequently for other types of ovarian cancer. Gastrointestinal cancer regimens are another option; these include 5-fluorouracil and oxaliplatin, or capecitabine and oxaliplatin. Data on heated intra-peritoneal chemotherapy (HIPEC) for mucinous ovarian cancer are scarce, but HIPEC may be worth considering. For patients with recurrence or progression on first-line chemotherapy, we advocate enrollment in a clinical trial if one is available. For this reason, it may be beneficial to perform molecular testing in all patients with recurrent or progressive mucinous ovarian cancer.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Kuroda, K., et al. (2023). "Therapeutic efficacy of the optimization of thyroid function, thrombophilia, immunity and uterine milieu (OPTIMUM) treatment strategy on pregnancy outcomes after single euploid blastocyst transfer in advanced age women with recurrent reproductive failure." Reproductive Medicine and Biology 22(1): e12554.
	Purpose: To clarify the efficacy of the OPtimization of Thyroid function, Thrombophilia, IMmunity and Uterine Milieu (OPTIMUM) treatment strategy on pregnancy outcomes after euploid blastocyst transfer in advanced age women with recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL).; Methods: Between January 2019 and May 2022, 193 consecutive women aged ≥40 years with RIF and/or RPL received single euploid blastocyst transfer. Before embryo transfer, 127 women underwent RIF/RPL testing. Chronic endometritis was treated with mainly antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. We compared pregnancy outcomes in the women who did and did not receive the OPTIMUM treatment strategy.; Results: Women with RIF/RPL in the OPTIMUM group had significantly higher clinical pregnancy and livebirth rates than did those in the control group (clinical pregnancy rate of 71.7% and 45.5%, p < 0.001; livebirth rate of 64.6% and 39.4%, p = 0.001, respectively). However, preimplantation genetic testing for aneuploidy with and without OPTIMUM promoted low miscarriage rates with no significant difference between them (9.9%, and 13.3%, respectively; p = 0.73).; Conclusions: The OPTIMUM treatment strategy improved clinical pregnancy rates after single euploid blastocyst transfer; but not miscarriage rates.; Competing Interests: All authors have no conflicts of interest to declare, relevant to this study. Tetsuo Maruyama is an Editorial Board member of Reproductive Medicine and Biology and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. Human rights statement and informed consent: This study was approved by the local ethics committee of Sugiyama Clinic (No. 18–002 and 22–008). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1964 and its later amendments. The data that support the findings of this study are available on request from the corresponding author. (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Kuroda, K., et al. (2023). "Therapeutic efficacy of gentle endometrial curettage on antibiotic-resistant chronic endometritis in infertile women." Reproductive Medicine and Biology 22(1): e12525.
	Purpose: To identify the efficacy of endometrial curettage on antibiotic-resistant chronic endometritis (CE) in infertile women. Method(s): Of 1580 women with CE, 87 with antibiotic-resistant CE after two to five cycles of antibiotic treatment were recruited between 2019 and 2021. The women who underwent endometrial curettage without applying any force and, in the subsequent menstrual cycle, endometrial sampling for CD138 immunostaining without antibiotic use. Pregnancy outcomes after in vitro fertilization treatment were analyzed in women who did not desire endometrial curettage and in those with cured and persistent CE after endometrial curettage. Result(s): In 64 women who underwent endometrial curettage, the number of CD138-positive cells decreased from 28.0 +/- 35.3 to 7.7 +/- 14.0 (p < 0.0001), and CE in 41 women (64.1%) was cured (<5 CD138-positive cells). The pathological findings detected 3.1% of endometrial hyperplasia and 1.6% of endometrial cancer. The ongoing pregnancy rates in women aged <=42 without endometrial curettage were significantly lower than those of women with cured and persistent CE (26.7%, 67.6%, and 57.1%, respectively, p = 0.03). Conclusion(s): Gentle endometrial curettage for antibiotic-resistant CE significantly decreased the number of CD138-positive cells, resulting in improved pregnancy outcomes regardless of remaining CE. Endometrial curettage is also important as a screening for endometrial malignancy.Copyright © 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

Kurosaki, A. (2023). "[Ⅲ. Current Topics for the Administration of PARP Inhibitors for Primary Treatment of Ovarian Cancer]." Gan to kagaku ryoho. Cancer & chemotherapy 50(2): 165-170.
	
Kurtz, J. E., et al. (2022). "LBA30 Phase III ATALANTE/ov29 trial: Atezolizumab (Atz) versus placebo with platinum-based chemotherapy (Cx) plus bevacizumab (bev) in patients (pts) with platinum-sensitive relapse (PSR) of epithelial ovarian cancer (OC)." Annals of Oncology 33(Supplement 7): S1397.
	Background: Standard Cx for PSROC (> 6 months after last platinum dose) includes carboplatin plus pegylated liposomal doxorubicin (CbD) or gemcitabine (CbG) or paclitaxel (CbP) with or without bev. ATALANTE/ENGOT-ov29 (NCT02891824) is the first Phase III trial to evaluate Atz with Cx and bev for pts with PSROC. Method(s): Eligible pts had PSROC and <=2 prior lines of Cx. Pts were randomised 2:1 to Atz (1200 mg, d1, q3w or 800 mg, d1&15, q4w with CbD up to 24 months [m]) or placebo (Pbo) with Cx at investigator-choice (CbD/CbG/CbP, 6 cycles) plus bev (15 mg/kg, d1, q3w or 10 mg/kg, d1&15, q4w), stratified by platinum-free interval, PD-L1 status on biopsy at study entry and Cx cohort. The co-primary endpoints are investigator-assessed progression-free survival (PFS) in the intent-to-treat (ITT) and PD-L1-positive (>=1% IC per tumour area) pts. Type I error was set at 0.025. Result(s): From 10/2016 to 09/2019, 614 pts were randomized to Atz (n=410) or Pbo (n=204). Pts characteristics were balanced; Cx: CbD (63%), CbG (29%), CbP (8%), 1 (74%) or 2 (26%) prior lines, prior bev (62%). PD-L1 status was positive, negative, unknown in 38%, 49% and 13% of pts. Median follow-up was 36 m. The median PFS in the ITT pts was 13.5 and 11.2 m for the Atz and Pbo arms (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99; P =.041), and 15.2 vs 13.1 m in the PD-L1-positive pts (HR, 0.86; 95% CI, 0.63 to 1.16; P =.30). At 333/491 planned events in the ITT pts, the median overall survival (OS) in the Atz and Pbo arms was 35.4 vs 30.6 m (HR, 0.81; 95% CI, 0.65 to 1.01). Grade >=3 AEs and immune AEs were reported in 88% vs 86% and in 13% vs 8% of Atz and pbo pts respectively. There were five treatment related AEs of death (Atz, n=3; pbo, n=2). There was no significant difference in global health-related quality of life scores. Conclusion(s): The ATALANTE trial evaluating the addition of Atz to standard therapy of PSROC pts did not meet its PFS co-primary endpoints in the ITT and PD-L1-positive pts. Encouraging OS data warrant further analyses with longer follow-up. Further research on ATALANTE biopsy samples is warranted to better decipher the immunological landscape of PSROC. Clinical trial identification: 2015-005471-24. Editorial acknowledgement: Jennifer Kelly, Medi-Kelsey Limited. Legal entity responsible for the study: ARCAGY-GINECO. Funding(s): F. Hoffmann - La Roche Ltd. Disclosure: J.E. Kurtz: Financial Interests, Personal, Advisory Board: Tesaro, Merck Serono, Clovis, AstraZeneca, GSK; Financial Interests, Personal, Other, Travel expenditure: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Invited Speaker: Astra Zeneca, GSK, Bristol Myers Squib; Non-Financial Interests, Principal Investigator: Roche; Other, Immediate member family employed by Merck Sharp Dohme: Merck Sharp Dohme. E. Pujade-Lauraine: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, GSK; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, GSK; Financial Interests, Personal, Writing Engagements: Astra Zeneca, GSK; Financial Interests, Personal, Other, IDMC: INCYTE; Non-Financial Interests, Institutional, Full or part-time Employment: ARCAGY-GINECO; Non-Financial Interests, Institutional, Other, CEO: ARCAGY-Research. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de Espana, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann -La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de Espana SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, L adership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research ( via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). M.J. Rodrigues: Financial Interests, Personal, Invited Speaker: ASTRA ZENECA, GlaxoSmithKline, Merck Sharp and Dohme, Immunocore; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb, Merck Sharp and Dohme, Daiichi Sankyo; Non-Financial Interests, Invited Speaker: Societe Francaise du Cancer. N. de Gregorio: Financial Interests, Personal, Other, Travel expenses: ASTRA ZENECA; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Myriad, GSK, MSD, Clovis, PharmaMar; Non-Financial Interests, Other: AGO Study group, Organkommission Ovar. J. Martinez-Garcia: Financial Interests, Personal, Advisory Board: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar; Financial Interests, Personal, Invited Speaker: Clovis Oncology, GSK-Tesaro, PharmaMar; Financial Interests, Personal, Other, Travel/accommodation/expenses for meeting: GSK-Tesaro, PharmaMar. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD. M.A. Mouret Reynier: Financial Interests, Personal, Other, Board participations and symposiums: Pfizer, Roche, Myriad, Astra-Zeneca, MSD, Lilly, Novartis, Eisai; Financial Interests, Institutional, Other, Clinical Trials: BMS, AbbVie, Roche, Novartis, MSD, Astra-Zeneca. F. Selle: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK-Tesaro, MSD, Sandoz (Novartis), Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Roche, GSK-Tesaro, ASTRA ZENECA, Immunogen, MSD, Incyte, Agenus. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, ipsen, BMS, Bayer, Esai; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Astellas; Financial Interests, Institutional, Invited eaker: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Other, Other, travel: MSD, GSK. E. Bultot Boissier: Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Other, ESMO Member: ESMO. A. Floquet: Financial Interests, Personal, Other, Consultancy: GSK; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis Oncology; Financial Interests, Invited Speaker, French coordinator - DUO Trial: AstraZeneca; Financial Interests, Invited Speaker, French coordinator- MIRASOL Trial: Immunogen. P. Heudel: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Seagen; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: AstraZeneca. F. Heitz: Financial Interests, Personal, Invited Speaker: Amedes, Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca, NovoCure, PharmaMar, Roche; Financial Interests, Institutional, Other, Trial Chair: Newoncology. All other authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Kusin Samuel, B., et al. (2023). "Empiric versus culture-based antibiotic therapy for UTIs in menopausal women." World Journal of Urology 41(3): 791-796.
	Purpose: To assess the benefits and risks associated with empiric prescription of antibiotic therapy for treatment of a urinary tract infection (UTI).; Methods: Following IRB approval menopausal women presenting with a symptomatic UTI to a single urology clinic were prospectively assigned to one of the two treatment groups based on day of presentation: culture-based treatment (CB) (Monday, Tuesday, Wednesday) or empiric treatment (ET) (Thursday, Friday) and started on nitrofurantoin (NF) pending culture results. Both groups were contacted at 7 and 14 days following treatment. Side effects and answers to a standardized questionnaire (UTISA) were recorded. Success was defined as a total UTISA score < 3. Any NF retreatment, use of another antibiotic therapy, or extension of the original antibiotic course was considered treatment failures.; Results: From July 2020 to March 2022, 65 women with 80 UTI events were included in the study, with CB treatment used for 60 UTIs and ET used for 23 UTIs. At 7 days after start of treatment, questionnaire failure rate was 44% (20/45) for the CB group and 16% (3/19) for the ET group (P = 0.076). At 14 days following start of treatment, questionnaire failure rate was 31% (13/42) for the CB group and 17% (3/18) for the ET group (P = 0.3). In the ET group, 11% of cultures were found to be resistant to NF.; Conclusion: Outcomes for the empiric treatment of uncomplicated UTI with NF at both 7 and 14 days are not significantly different than outcomes with culture-based treatment. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kutay, Y., et al. (2021). "The effect of perioperative lidocaine infusion on postoperative pain and postsurgical recovery parameters in gynecologic cancer surgery." The Clinical Journal of Pain 37(2): 126-132.
	Objectives: The primary objective of this prospective nonblinded randomized study was to investigate the effect of perioperative systemic lidocaine infusion on pain control after major gynecologic oncology surgery. Patient-reported outcomes, postoperative recovery parameters, and complications were secondary endpoints of the study. Materials and Methods: Seventy-five patients with American Society of Anesthesiologists I-III were divided into 3 groups based on perioperative analgesia methods-(1) opioid group: patient-controlled analgesia (PCA) with morphine; (2) lidocaine group: perioperative intravenous lidocaine infusion, plus PCA with morphine; and (3) the epidural group: PCA with bupivacaine. The Visual Analog Scale (VAS) was recorded postoperatively. In addition, nausea-vomiting, time to first oral intake, time to first ambulation, time to first flatus, and length of hospital stay were recorded. Results: VAS scores (rest) at 24 hours and VAS scores (cough) at 12 and 24 hours were significantly lower in the epidural group than in the opioid group (P<0.05). VAS scores were found to be similar between the lidocaine and epidural group. The nausea-vomiting incidence was lower in the lidocaine group than in the opioid group (P<0.05). Compared with the other 2 groups, the first flatus time was shorter in the lidocaine group (P<0.05). Discussion: Perioperative lidocaine infusion is effective as epidural analgesia, which is often advocated as the gold-standard analgesic technique for abdominal surgery and is superior to the others in terms of time to first flatus and the incidence of nausea-vomiting. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Kutsenko, I. I., et al. (2023). "Dequalinium chloride in the treatment of vaginal infections." Voprosy Ginekologii, Akusherstva i Perinatologii 22(3): 63-78.
	The most common inflammatory and infectious diseases of the lower genital tract include bacterial vaginosis (BV), vulvovagi-nal candidiasis (VVC), aerobic vaginitis, and mixed infections. Standard modern therapies show acceptable but short-term efficacy in most cases, and high recurrence rates and increased antimicrobial resistance remain an unresolved issue. Moreover, vaginal infections are associated with different adverse outcomes both in terms of higher incidence of infertility among couples and gestational complications, having a serious impact on patients' quality of life. The determination of appro-priate management tactics for these women, especially in mixed infections, is quite a challenge for clinicians. This meta-analysis evaluates the efficacy of topical therapy with antimicrobial antiseptics containing dequalinium chloride for various types of vaginal infections. Objective. To analyze the clinical and microbiological efficacy and safety of dequalinium chloride in the treatment of vaginal infections of different etiologies. Materials and methods. A review of selected scientific publications over the past 40 years on the use of dequalinium chloride in the treatment of vaginal infections with assessing the efficacy and safety of its topical use in women was conducted. A total of 4,783 patients (from 26 studies) were included. Results. Dequalinium chloride is an antimicrobial antiseptic agent with broad bactericidal and fungicidal activity and low systemic absorption after vaginal administration. At the same time, dequalinium chloride has similar clinical efficacy to clindamycin when used topically in the treatment of bacterial vaginosis, and its broad antimicrobial activity appears to be most suitable for the treatment of mixed vaginal infections. In addition, the development of microbial resistance to this drug is unlikely due to its pluripotent mechanism of action and local application. Conclusion. The analysis showed that the current formulation of dequalinium chloride (10 mg vaginal tablets) as 6-day therapy with its broad spectrum of antimicrobial activity and good tolerability offers a safe and effective option for empiric therapy of various vaginal infections in daily practice.Copyright © 2023, Dynasty Publishing House. All rights reserved.

Kutuk, T., et al. (2023). "Tumor treating fields: narrative review of a promising treatment modality for cancer." Chinese Clinical Oncology 12(6): 64.
	Background and Objective: Tumor treating fields (TTFields) therapy have emerged as a potentially effective treatment for various malignancies by delivering low-intensity, intermediate-frequency electrical fields that disrupt many processes inside cells, resulting in the interruption of cell division in cancer cells. Additionally, TTFields therapy has been found to be synergistic with existing therapeutic approaches. In this review, we provide an introduction and background to the primary mechanisms of TTFields and discuss the emerging preclinical and clinical outcomes of this novel cancer treatment technology. Method(s): We performed a literature search on PubMed, ClinicalTrials.Gov, and Google Scholar using the terms 'TTFields' and 'cancer'. We included studies, review articles, and editorials published in English from 1st January 2000 to 1st October 2023. All obtained publications were reviewed and their key references are cross-checked to ensure a balanced and high-quality review. Key Content and Findings: Clinical studies reported to date have demonstrated the survival advantage of TTFields therapy in newly diagnosed glioblastoma (GBM), non-small cell lung cancer (NSCLC), and meaningful clinical activity in recurrent GBM (rGBM) and malignant pleural mesothelioma. Moreover, TTFields therapy has exhibited promising safety profiles across a diverse range of cancers including pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, NSCLC, and gastric cancer, when combined with cytotoxic chemotherapy and/or immunotherapy regimens, suggesting broad applicability as an added treatment modality. Conclusion(s): Based on preclinical and clinical studies, TTFields therapy show promise as a potential treatment option for patients with a number of different malignancies, offering a favorable safety profile and the potential for significant clinical benefit. Further research is warranted to establish the optimal treatment parameters and identify specific patient subgroups that may derive the greatest advantage from this treatment modality.Copyright © Chinese Clinical Oncology. All rights reserved.

Kuznicki Michelle, L., et al. (2021). "Fertility-Sparing Surgery for Early-Stage Cervical Cancer: A Systematic Review of the Literature." Journal of Minimally Invasive Gynecology 28(3): 513.
	Objective: This systematic review aimed to evaluate oncologic and reproductive outcomes after fertility-sparing surgery (FSS) for early-stage cervical cancer (early CC).; Data Sources: Ovid MEDLINE, Ovid EMBASE, and Cochrane CENTRAL were searched from 1980 to the present using Medical Subject Headings terms; other controlled vocabulary terms; and keywords related to fertility, cervical cancer, and surgical techniques.; Methods of Study Selection: A total of 2415 studies were screened, with 53 studies included. Studies reporting recurrences with a median follow-up of 12 months in early CC (International Federation of Gynecology and Obstetrics 2009 stages IA with lymphovascular space invasion, IB, or IIA) of traditional histologic type undergoing FSS were included.; Tabulation, Integration, and Results: The studies were grouped by intervention, including vaginal radical trachelectomy (VRT), abdominal radical trachelectomy (ART), minimally invasive radical trachelectomy (MIS-RT), and conization or simple trachelectomy (ST), and studies involving neoadjuvant chemotherapy (NACT). Combined rates of recurrence (RR), cancer death (CDR), pregnancy (PR), and live birth (LBR) were calculated per procedure on the basis of all included studies that reported outcomes on that procedure. The results were as follows: VRT: RR 4%, CDR 1.7%, PR 49.4%, and LBR 65.0% ART: RR 3.9%, CDR 1.4%, PR 43.2%, and LBR 44.0% MIS-RT: RR 4.2%, CDR 0.7%, PR 36.2%, and LBR 57.1% Cone or ST: RR 4.2%, CDR 0.8%, PR 55.1%, and LBR 71.9% NACT: RR 7.5% and CDR 2.0% CONCLUSION: FSS of early CC with VRT, ART, or MIS-RT have comparable oncologic outcomes in carefully selected patients, with reproductive outcomes favoring VRT. Data on nonradical FSS with cone or ST are less robust but support similar oncologic outcomes to radical trachelectomy with fewer reproductive complications. NACT in this setting requires more investigation before routine implementation into practice. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Kvale, E., et al. (2024). "Survivorship Care for Women Living With Ovarian Cancer: Protocol for a Randomized Controlled Trial." JMIR Research Protocols 13: e48069.
	BACKGROUND: Ovarian cancer ranks 12th in cancer incidence among women in the United States and 5th among causes of cancer-related death. The typical treatment of ovarian cancer focuses on disease management, with little attention given to the survivorship needs of the patient. Qualitative work alludes to a gap in survivorship care; yet, evidence is lacking to support the delivery of survivorship care for individuals living with ovarian cancer. We developed the POSTCare survivorship platform with input from survivors of ovarian cancer and care partners as a means of delivering patient-centered survivorship care. This process is framed by the chronic care model and relevant behavioral theory. OBJECTIVE: The overall goal of this study is to test processes of care that support quality of life (QOL) in survivorship. The specific aims are threefold: first, to test the efficacy of the POSTCare platform in supporting QOL, reducing depressive symptom burden, and reducing recurrence worry. In our second aim, we will examine factors that mediate the effect of the intervention. Our final aim focuses on understanding aspects of care platform design and delivery that may affect the potential for dissemination. METHODS: We will enroll 120 survivors of ovarian cancer in a randomized controlled trial and collect data at 12 and 24 weeks. Each participant will be randomized to either the POSTCare platform or the standard of care process for survivorship. Our population will be derived from 3 clinics in Texas; each participant will have received some combination of treatment modalities; continued maintenance therapy is not exclusionary. RESULTS: We will examine the impact of the POSTCare-O platform on QOL at 12 weeks after intervention as the primary end point. We will look at secondary outcomes, including depressive symptom burden, recurrence anxiety, and physical symptom burden. We will identify mediators important to the impact of the intervention to inform revisions of the intervention for subsequent studies. Data collection was initiated in November 2023 and will continue for approximately 2 years. We expect results from this study to be published in early 2026. CONCLUSIONS: This study will contribute to the body of survivorship science by testing a flexible platform for survivorship care delivery adapted for the specific survivorship needs of patients with ovarian cancer. The completion of this project will contribute to the growing body of science to guide survivorship care for persons living with cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT05752448; https://clinicaltrials.gov/study/NCT05752448. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48069.

Kwak Han, D., et al. (2023). "A comparative study between transanal and transabdominal approaches in treatment of complete rectal prolapse." International Journal of Colorectal Disease 38(1): 78.
	Formulating clear guidelines for the most reliable treatment methods for complete rectal prolapse appears challenging. The authors designed this study to compare the results according to the approaches for female complete rectal prolapse and to suggest a more effective method. The transanal and abdominal groups showed differences in operating time, hospital stay, and recurrence rate. However, both groups demonstrated improvement in postoperative functional evaluation.; Purpose: There is a wide variety of surgical methods to treat rectal prolapse; however, to date, no clear agreement exists regarding the most effective surgical method. This study was designed to compare the results according to the surgical approach for complete rectal prolapse in women.; Methods: This study was conducted from March 2016 to February 2021 on female patients with rectal prolapse who underwent surgery. First, all patients were classified into mucosal and complete layer groups to confirm the difference in results between the two groups, and only complete layer prolapse patients were divided into transanal and abdominal approaches to compare parameters and functional outcomes in each group.; Results: A total of 180 patients were included, with an average age of 71.7 years and 102 complete prolapses. The complete layer group was found to have more abdominal access, longer operating time, and higher recurrence rates compared to the mucosal layer group. (p<0.001) When targeting only the complete layer patients, there were 65 patients with the transanal and 37 with the abdominal (laparoscopic) approaches. The abdominal approach group had a longer operating time and hospital stay (p<0.001, respectively) and lower recurrence rate than the transanal group (transanal vs. abdominal, 38% vs. 10.8%, p=0.003), while the Wexner constipation and incontinence scores showed improved results in both groups.; Conclusion: Although operating time and hospitalization period were shorter in the transanal group, laparoscopic abdominal surgery is a procedure that can reduce the recurrent rate for complete rectal prolapse. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Kwok, S. S., et al. (2019). "A Systematic Review of Potential Therapeutic Use of Lycium Barbarum Polysaccharides in Disease." BioMed Research International 2019: 4615745.
	Objective. To evaluate the effect of Lycium barbarum polysaccharides in the treatment and/or prevention of diseases of different etiologies and systems. Methods. We performed an Entrez PubMed literature search using keywords "lycium", "barbarum", "polysaccharides", "anti-fibrotic", "anti-apoptotic", "anti-oxidizing", "anti-aging", "neuroprotection", "metabolism", "diabetes", "hyperlipidemia", "neuroprotection", and "immunomodulation" on the 14th of August 2018, resulting in 207 papers, of which 20 were chosen after filtering for 'English language' and 'published within 10 years' as well as curation for relevance by the authors. Results. The 20 selected papers included 2 randomized control trials (1 double-blinded RCT and 1 double-blinded placebo-controlled RCT), 11 in vivo studies, 5 in vitro studies, 1 study with both in vivo and in vitro results, and 1 chemical study. There is good evidence from existing studies on the antifibrotic, antioxidizing, neuroprotective, anticancer, and anti-inflammatory effects of Lycium barbarum polysaccharides. However, there is a need for further studies in the form of large-scale clinical trials to support its use in humans. There is also significant potential for LBP as a safe and effective topical treatment in ocular surface diseases, owing to promising in vitro results and a lack of demonstrated toxic effects to corneal epithelial cells. Conclusion. Results from existing studies suggest that LBP is a promising therapeutic agent, particularly in the management of liver disease, hyperlipidemia, and diabetes. One major limitation of current research is a lack of standardization and quality control for the LBP used. The availability of research-grade LBP will inevitably promote future research in this field worldwide.Copyright © 2019 Sum Sum Kwok et al.

Kwon, C. Y., et al. (2020). "Therapeutic Effects and Mechanisms of Herbal Medicines for Treating Polycystic Ovary Syndrome: A Review." Frontiers in Pharmacology 11: 1192.
	Background: Polycystic ovary syndrome (PCOS) is one of the most common disorders of endocrinology in reproductive-age women. In this study, we reviewed data on the effects and underlying mechanisms of herbal medicines used in the treatment of PCOS in laboratory studies. Method(s): Articles published in English up to June 30, 2018 were searched in Medline and EMBASE. We extracted data regarding herbal intervention; target cell (or animal model) usage; method of herbal extraction; route of administration; dosage and periods; and outcomes of the compounds isolated from herbs, individual herbal extracts, and herbal formula decoctions. We summarized the actions and the mechanisms underlying the beneficial effects of herbal medicines on PCOS. Result(s): A total of 27 studies involving 22 herbal medicines reported their efficacy on PCOS. The herbal interventions in the 27 studies comprised four compounds isolated from herbs (6 studies), nine individual herbal extracts (11 studies), and nine herbal formula decoctions (10 studies). Herbal medicines normalized female hormones, diminished male hormones, recovered the estrous cycle, ameliorated insulin resistance, and improved lipid metabolism in PCOS. The mechanisms underlying the beneficial effects of herbal medicines on PCOS were found to be associated with anti-inflammation, anti-oxidative stress, inhibition of autophagy and/or apoptosis, and ovarian nerve growth factor reduction. Conclusion(s): Herbal medicines are thought to be promising resources in the development of effective therapeutic agents for PCOS. Further studies that include methodological quality assessment and quantitative synthesis of outcomes are recommended.© Copyright © 2020 Kwon, Cho and Park.

Kwon, C.-Y., et al. (2020). "Herbal medicine in women undergoing in vitro fertilization/ intracytoplasmic sperm injection: A systematic review and meta-analysis." Complementary Therapies in Medicine 53: 102528.
	A combination of in vitro fertilization (IVF) and herbal medicine (HM) has been widely used in Asian countries. We conducted a systematic review of randomized controlled trials (RCTs) that evaluated the effects of HM as an adjunct to IVF and reported the pregnancy outcomes, including the live birth rate (LBR) and clinical pregnancy rate (CPR). HM was consistently more likely to increase the LBR (RR 1.34, 95 % CI 1.05-1.72) and CPR (RR 1.38, 95 % CI 1.29-1.49) than those not receiving adjunctive treatment. The CPR in the HM treatment group was also improved compared to the placebo group (RR 1.85, 95 % CI 1.42-2.42). The adverse events were not significantly different between the HM and control groups. These findings indicate that HM may have beneficial effects on pregnancy outcomes in females undergoing IVF. Large-scale, long-term RCTs with robust methodological inputs are needed to clarify the role of HM. (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Kyeong, H.-K., et al. (2023). "Effects of long-term intermittent pharmacological therapy with ulipristal acetate on reducing the volume of uterine fibroids and relieving symptoms." Minerva Obstetrics and Gynecology 75(3): 236-242.
	Background: The aim of this study was to compare the effects of a 12-week course and four repeated 12-week courses of daily 5 mg ulipristal acetate (UPA) on reducing the volume and relieving symptoms of uterine fibroids.; Methods: From 2016 to 2019, 287 female patients with uterine fibroids diagnosed using ultrasonography were recruited. The patients received four 12-week course treatments of daily UPA administration in the first and fourth sessions, respectively. During the first and fourth courses of UPA, we measured the volume of the fibroids using ultrasonography to study the effect on volume reduction. The measured outcomes included symptomatic relief and adverse effects.; Results: After the first UPA treatment course, menorrhagia was improved in 82.2% of patients. A total of 59.5% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 160.9 cm 3 to 104.6 cm 3 . After the fourth treatment course, 87.4% of patients reported decreased bleeding. A total of 67.2% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 171.7 cm 3 to 106.5 cm 3 . In 64 (38.1%) patients in group A and 36 (30.3%) in group B, the fibroid volume increased. Among them, 72% of patients showed improved symptoms.; Conclusions: Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.

Kyriazoglou, A., et al. (2021). "The systemic treatment of uterine leiomyosarcomas: A systematic review. No news is good news?" Medicine 100(13): e25309.
	Background: Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a lot of unanswered questions regarding the ideal therapeutic approach.; Methods: We have conducted a systematic review of the treatment strategies of uterine leiomyosarcomas for the last ten years.; Results: Adjuvant chemotherapy is still a matter of dilemma. Doxorubicin based chemotherapy or the combination of Gemcitabine-Docetaxel are the regimens of choice for the first line setting. Beyond the first line, there are several options;, including chemotherapy, targeted therapy, and recently efforts of introducing immunotherapy to the therapeutic armamentarium of clinicians treating uterine leiomyosarcomas.; Conclusions: Despite the efforts of the clinicians dealing with uterine leiomyosarcomas, the optimal therapeutic algorithm is yet to be described.; Competing Interests: The authors have no conflicts of interest. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

La Russa, M., et al. (2021). "Ultra-minimally invasive approaches for endometrial cancer treatment: review of the literature." Minerva Medica 112(1): 31-46.
	Introduction: We conducted a systematic review to evaluate the outcomes and role of ultra-minimally invasive surgical approaches for treatment of women diagnosed with endometrial cancer. Although, there is no agreed definition of the term "ultraminimal," we considered the hysteroscopic surgery, single-port surgery, mini/microlaparoscopy and percutaneous laparoscopy as surgical approaches that would best fit this description.; Evidence Acquisition: The current systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. We performed a literature search using MEDLINE (PubMed), EMBASE and Cochrane Library databases for English-language studies published before August 1, 2020. We used the following keywords including "endometrial cancer," "endometrial malignancy," "fertility-sparing or preserving," "hysteroscopy," "hysteroscopic resection," "dilatation and curettage," "ultra-minimally invasive surgery," "progestin therapy," "hormone therapy," "single port," "single-site," "minilaparoscopy," "microlaparoscopy," "percutaneous" and "3 mm laparoscopy."; Evidence Synthesis: A total of 21 studies, reporting on 229 patients were included. 219 (95.6%) of the patients were premenopausal. Among premenopausal women, complete disease response was reported in 186 (84.9%) patients. The complete response rate was 77.1% in patients who underwent focal or extensive endometrial resection, 90.9% in patients who had the two-step approach and 88.9% in the group of patients treated with the three-step technique. Among 98 women who wished and attempted to conceive, 65 (66.3%) women became pregnant. Recurrent disease was diagnosed in 26 of 219 (11.9%) patients. No surgical complications were reported. In 10 postmenopausal patients that underwent hysteroscopic resection, no recurrences were detected after 5 years of follow-up. We identified 11 studies that reported on the use single-port laparoscopic surgery and included a total of 447 patients. The rate of intraoperative and postoperative complications was 2.6% and 5.2%, respectively. The majority of the studies did not report on the duration of follow-up or oncological outcomes. Ten studies, including 296 patients, investigated the role of single-port robotic-assisted laparoscopy. The overall rate of intraoperative and postoperative complications was 1.0% and 7.1%, respectively. Two studies, including 38 patients, reported on the role of minilaparoscopy. None of these cases required conversion to laparotomy. Data on overall survival in the cohort of patients that underwent minilaparoscopy were not reported. We found only one publication reporting on the use of percutaneous laparoscopy. This prospective study included 30 patients. No complication was reported, and with a median follow-up time of 14 months (range 12-36) no recurrences were diagnosed.; Conclusions: Several ultra-minimally invasive surgical techniques have been developed and implemented in selected patients with endometrial cancer. The results of this review support the feasibility and perioperative safety of these approaches, while long-term outcomes are not adequately studied. However, further work is required in standardization of the techniques, in determining the learning curve of the operator and establishing their oncological safety.

Laan Janna, J., et al. (2023). "The Effect of Contemporary Brachytherapy Practices on Prognosis in Women with Locally Advanced Cervical Cancer." Current oncology (Toronto, Ont.) 30(4): 4275-4288.
	(1) Background: Over the past two decades use of new imaging modalities and the adaptation of applicators have allowed for advances in volumetric (3D) imaging-based brachytherapy practices for patients with locally advanced cervical cancer. The aim of this study was to compare the oncological outcome and toxicity for three consecutively introduced brachytherapy practices in a large single-center cohort; (2) Methods: Patients treated for cervical cancer with primary radiotherapy and curative intent were consecutively included in this retrospective, single-center cohort study from 2006 to 2019. This cohort was divided into three groups (CT, MRI, and MRI+needles) based on the timing of the introduction of a novel brachytherapy practice; 3D brachytherapy planning using CT- and MRI-guided adaptive brachytherapy and the use of parametrial interstitial needles, respectively. Actuarial estimates were compared between groups. Multivariable Cox regression analyses were performed to correct for other risk factors. Crude rates of severe (≥grade 3) late toxicity were reported; (3) Results: A total of 397 patients were included in this cohort. At a median follow-up of 40 months (interquartile range (IQR) 22-62), actuarial 3-year local control, pelvic control, disease-free survival, and overall survival for the entire cohort were 91% (95% (Confidence Interval (CI)) 88-94), 88% (95% CI 84-91), 69% (95% CI 64-74), and 75% (95% CI 70-79), respectively). Local control, disease-free survival, and overall survival were significantly improved in the MRI+needles group compared to the CT group ( p = 0.040, p = 0.004, and p < 0.001, respectively). Independent risk factors for overall survival were treatment in either the CT or MRI group (vs. MRI+needles), older age at diagnosis, adeno (squamous) carcinoma, FIGO stage III/IV, and lymph node metastases. The crude rate of severe late toxicity was 27% in the CT, 26% in the MRI, and 20% in the MRI+needles group; (4) Conclusions: Prognosis in women with locally advanced cervical cancer treated with state-of-the-art MRI-guided adaptive brachytherapy combined with parametrial interstitial needles compares favorably to patients treated with more traditional CT only based brachytherapy.

Labidi-Galy, S. I., et al. (2023). "Association of location of BRCA1 and BRCA2 mutations with benefit from olaparib and bevacizumab maintenance in high-grade ovarian cancer: phase III PAOLA-1/ENGOT-ov25 trial subgroup exploratory analysis." Annals of oncology : official journal of the European Society for Medical Oncology 34(2): 152-162.
	Background: In the phase III PAOLA-1 study, the addition of maintenance olaparib to bevacizumab in patients with newly diagnosed high-grade ovarian cancer (HGOC) resulted in prolonged progression-free survival (PFS), particularly for homologous recombination deficiency-positive tumors, including those with a BRCA mutation (BRCAm). The magnitude of benefit from olaparib and bevacizumab according to the location of mutation in BRCA1/BRCA2 remains to be explored.; Patients and Methods: Patients with advanced-stage HGOC responding after platinum-based chemotherapy + bevacizumab received maintenance therapy bevacizumab (15 mg/kg q3w for 15 months) + either olaparib (300 mg b.i.d. for 24 months) or placebo. PFS was analyzed in the subgroup of patients with BRCA1m/BRCA2m according to mutation location in the functional domains of BRCA1 [Really Interesting Gene (RING), DNA-binding domain (DBD), or C-terminal domain of BRCA1 (BRCT)] and BRCA2 [RAD51-binding domain (RAD51-BD); DBD].; Results: From 806 randomized patients, 159 harbored BRCA1m (19.7%) and 74 BRCA2m (9.2%). BRCA1m in RING, DBD, and BRCT domains was detected in 18, 40, and 33 patients, and BRCA2m in RAD51-BD and DBD in 36 and 13 patients, respectively. After a median follow-up of 25.5 months, benefit from maintenance olaparib + bevacizumab was observed irrespective of location of BRCAm. The benefit was particularly high for those with BRCA1m located in the DBD, with 24-month PFS estimated to be 89% and 15% [olaparib + bevacizumab versus placebo + bevacizumab hazard ratio = 0.08 (95% confidence interval 0.02-0.28); interaction P = 0.03]. In BRCA2m patients, 24-month PFS rates for those with mutations located in the DBD were 90% and 100% (olaparib + bevacizumab versus placebo + bevacizumab), respectively.; Conclusions: Advanced-stage BRCA-mutated HGOC patients reported PFS benefit from maintenance olaparib and bevacizumab regardless of mutation location. The benefit is particularly high for patients with mutations located in the DBD of BRCA1. Mutations located in the DBD of BRCA2 are also associated with excellent outcome.; Competing Interests: Disclosure SILG: consulting or advisory role (AstraZeneca). MR: consulting or advisory role (AstraZeneca, GlaxoSmithKline, Merck, Sharp & Dohme), research funding (Bristol Myers Squibb, Merck, Sharp & Dohme). JEK: consulting or advisory role (AstraZeneca, Bristol Myers Squibb, Clovis, Eisai, GlaxoSmithKline), travel, accommodations, expenses (Clovis, Eisai, GlaxoSmithKline). FH: honoraria (AstraZeneca, Clovis, GlaxoSmithKline, NovoCure, PharmaMar, Roche), consulting or advisory role (Amedes, AstraZeneca, Clovis, GlaxoSmithKline, NovoCure, PharmaMar, Roche), research funding (AstraZeneca, Roche). IR: consulting or advisory role (AstraZeneca, Clovis Oncology, GlaxoSmithKline), speakers’ bureau (AstraZeneca, GlaxoSmithKline, PharmaMar, Roche), travel, accommodations, expenses (AstraZeneca, Clovis, GlaxoSmithKline, PharmaMar, Roche), research funding (GlaxoSmithKline, Roche). SN: speakers’ bureau (AstraZeneca, Chugai, Merck, Sharp & Dohme, Mochida). IV: consulting or advisory role (Agenus, Aksebio, Amgen, AstraZeneca, Bristol Myers Squibb, Carrick Therapeutics, Clovis, Deciphera, Eisai, Elevar Therapeutics, Genmab, GlaxoSmithKline, Immunogen, Jazz Pharmaceuticals, Karyopharm Therapeutics, Merck, Sharp & Dohme, Mersana, Millennium, Novartis, Novocure, OCTIMET Oncology NV, Oncoinvent, Roche, Seattle Genetics, Sotio, Verastem, Zentalis), travel, accommodations, expenses (Amgen, AstraZeneca, Merck, Sharp & Dohme, Roche, Tesaro), research funding (Amgen, Genmab, Oncoinvent, Roche). ER: consulting or advisory role (AstraZeneca), travel, accommodations, expenses (AstraZeneca, Bristol Myers Squibb), honoraria (AstraZeneca, Bristol Myers Squibb, Clovis, GlaxoSmithKline). CZ: consulting or advisory role (Amgen, AstraZeneca, Celgene, Eisai, Lilly, Novartis, Pfizer, PharmaMar, Quintiles IMS, Roche, Tesaro), travel, accommodations, expenses (Celgene, Istituto Gentili, Novartis, Pfizer, PharmaMar, Pierre Fabre, Roche, Tesaro), h noraria (Istituto Gentili, Pierre Fabre, Takeda, Teva), research funding (AbbVie, Array BioPharma, AstraZeneca, Celgene, Daiichi Sankyo, Medivation, Morphotek, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Roche, Seattle Genetics, Synthon, Tesaro). All other authors have declared no conflicts of interest. (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Labrune, E., et al. (2023). "When to cryopreserve ovarian tissue: Determining the effects of chemotherapy on the ovarian reserve by studying follicular density and apoptosis." Cytopathology : official journal of the British Society for Clinical Cytology 34(2): 146-153.
	Objectives: Patients scheduled to receive chemotherapy should be counselled on fertility preservation. Known gonadotoxic chemotherapies such as alkylating agents have a high risk of altering ovarian reserve. In some cases, the urgency of treatment requires the use of chemotherapy before fertility preservation, which will be carried out at a later stage. Usually the ovarian tissue is cryopreserved. The aim of our study is to investigate the impact of chemotherapies on follicular density and the apoptosis of reserve follicles.; Methods: We included 140 patients: 63 patients, mean age 18.8 years, were included in the group "no chemotherapy" (group A) and 77 patients, mean age 17.1 years, in the group "received chemotherapy before ovarian conservation" (group B). None of the patients had had pelvic radiotherapy prior to ovarian cryopreservation. The histological parameters studied were follicular density and the presence of malignant cells. We selected 12 patients from group A and 15 patients from group B, comparable in age and pathology, for whom we evaluated follicle apoptosis by immunostaining cleaved caspase-3.; Results: We demonstrated an inverse relationship between follicular density and age (p < 0.0001), as well as a lack of effect of chemotherapy on follicular density (p = 0.87). We showed the impact of various chemotherapies, especially with alkylating agents, on the apoptosis of ovarian follicles (p < 0.0001). Three patients had ovarian tissue infiltration, two of which were malignant.; Conclusion: This work underlines the fact that conservation of ovarian tissue after chemotherapy remains possible. (© 2022 The Authors. Cytopathology published by John Wiley & Sons Ltd.)

Laccetta, G., et al. (2023). "Symptoms of post-traumatic stress disorder in parents of preterm newborns: A systematic review of interventions and prevention strategies." Frontiers in Psychiatry 14: 998995.
	Background: Preterm birth and subsequent NICU admission can be a traumatic experience for parents who may subsequently develop post-traumatic stress (PTS) disorder (PTSD). Given that developmental issues are common among children of parents with PTSD, interventions for prevention and treatment are essential. Objective(s): To assess the most effective non-pharmacological interventions to prevent and/or treat PTS symptoms in parents of preterm newborns. Method(s): Systematic review performed in accordance with the PRISMA statements. Eligible articles in English language were searched in MEDLINE, Scopus, and ISI Web of Science databases using the following medical subject headings and terms: "stress disorder, post-traumatic," "parents," "mothers," "fathers," "infant, newborn," "intensive care units, neonatal," and "premature birth." The terms "preterm birth" and "preterm delivery" were also used. Unpublished data were searched in ClinicalTrials.gov website. All intervention studies published until September 9th, 2022 and including parents of newborns with gestational age at birth (GAb) <37 weeks which underwent >=1 non-pharmaceutical interventions for prevention and/or treatment of PTS symptoms related to preterm birth were included. Subgroup analyses were conducted by type of intervention. The quality assessment was performed according to the criteria from the RoB-2 and the "NIH Quality Assessment Tool for Before-After studies." Results: Sixteen thousand six hundred twenty-eight records were identified; finally, 15 articles (1,009 mothers, 44 fathers of infants with GAb <= 366/7 weeks) were included for review. A good standard of NICU care (effective as sole intervention: 2/3 studies) and education about PTSD (effective in association with other interventions: 7/8 studies) could be offered to all parents of preterm newborns. The 6-session Treatment Manual is a complex intervention which revealed itself to be effective in one study with low risk of bias. However, the effectiveness of interventions still remains to be definitively established. Interventions could start within 4 weeks after birth and last 2-4 weeks. Conclusion(s): There is a wide range of interventions targeting PTS symptoms after preterm birth. However, further studies of good quality are needed to better define the effectiveness of each intervention.Copyright © 2023 Laccetta, Di Chiara, De Nardo and Terrin.

Lackner Jeffrey, M., et al. (2022). "Study protocol and methods for Easing Pelvic Pain Interventions Clinical Research Program (EPPIC): a randomized clinical trial of brief, low-intensity, transdiagnostic cognitive behavioral therapy vs education/support for urologic chronic pelvic pain syndrome (UCPPS)." Trials 23(1): 651.
	Background: Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly, diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated with conventional medical therapies. Behavioral strategies, recommended as a first-line treatment for managing symptoms, are largely inaccessible, time and labor intensive, and technically complex. The Easing Pelvic Pain Interventions Clinical Research Program (EPPIC) is a clinical trial examining the efficacy of low-intensity cognitive behavioral therapy (Minimal Contact CBT or MC-CBT) for UCPPS and its durability 3 and 6 months post treatment. Additional aims include characterizing the operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC-CBT-induced symptom relief and pre-treatment patient variables that moderate differential response.; Methods: UCPPS patients (240) ages 18-70 years, any gender, ethnicity, and race, will be randomized to 4-session MC-CBT or a credible, non-specific education comparator (EDU) that controls for the generic effects from simply going to treatment. Efficacy assessments will be administered at pre-treatment, 2 weeks, and 3 and 6 months post treatment-week acute phase. A novel statistical approach applied to micro-analytic mediator assessment schedule will permit the specification of the most effective CBT component(s) that drive symptom relief.; Discussion: Empirical validation of a low-intensity self-management therapy transdiagnostic in scope has the potential to improve the health of chronic pelvic pain patients refractory to medical therapies, reduce social and economic costs, conserve health care resources, as well as inform evidence-based practice guidelines. Identification of change mechanisms and moderators of treatment effects can provide proactive patient-treatment matching fundamental to goals of personalized medicine.; Trial Registration: Clinicaltrials.gov NCT05127616. Registered on 9/19/21. (© 2022. The Author(s).)

LaCroix, A. and K. Ensrud (2023). "The flash dance of midlife: the Skylight 1 trial." Nature medicine 29(6): 1324-1325.
	
Laganà Antonio, S., et al. (2022). "Transvaginal versus Port-Site Specimen Retrieval after Laparoscopic Myomectomy: A Systematic Review and Meta-Analysis." Gynecologic and Obstetric Investigation 87(3-4): 177-183.
	Introduction: To date, there is no robust evidence suggesting whether transvaginal retrieval (TVSR) or port-site specimen retrieval (PSSR) after laparoscopic myomectomy (LM) may lead to better surgical outcomes. Considering this element, we aimed to compare surgical outcomes of TVSR versus PSSR after LM.; Methods: A search (PROSPERO ID: CRD42020176490) of international databases, from 1980 to 2020, in English language, was conducted. We selected studies that included women who underwent LM with TVSR compared with PSSR.; Results: We did not find significant differences for operative time (MD = -8.90; 95% CI: 30.00, 12.20; I2 = 87%), myoma retrieval time (MD = -1.85; 95% CI: 13.55, 9.85; I2 = 98%), blood loss (MD = -27.62; 95% CI: 178.68, 124.43; I2 = 91%), intra-operative complication rate (OR 0.51; 95% CI: 0.01-23.09; I2 = 69%), and hospital stay (MD = -0.14; 95% CI: 0.43, 0.15; I2 = 64%); we found a significant lower postoperative rescue analgesics utilization in the TVSR group compared with the PSSR group (OR 0.31; 95% CI: 0.16-0.61; I2 = 0).; Conclusion: TVSR and PSSR after LM showed comparable results for operative time and surgery-related complications. However, the need of postoperative rescue analgesics was lower in women who underwent TVSR. (© 2022 S. Karger AG, Basel.)

Łagowska, K. and S. Drzymała-Czyż (2022). "A low glycemic index, energy-restricted diet but not Lactobacillus rhamnosus supplementation changes fecal short-chain fatty acid and serum lipid concentrations in women with overweight or obesity and polycystic ovary syndrome." European Review for Medical and Pharmacological Sciences 26(3): 917-926.
	Objective: To evaluate if changes in fecal short-chain fatty acids (SCFA) content with an energy-restricted diet and with/without 12 × 109 CFU/day of Lactobacillus rhamnosus supplementation affect the abundance of selected gut bacteria and lipid profile in overweight and obese women with PCOS.; Patients and Methods: This randomized controlled trial involved 40 overweight and obese women with a mean age of 28.8 ± 4.8 years diagnosed with PCOS. The subjects were randomly assigned to an energy-restricted diet group (D group; n = 21) or energy-restricted diet + Lactobacillus rhamnosus supplementation group (DP group; n=19). SCFA, selected gut bacteria (Akkermansia muciniphila, Bifidobacterium longum, and Faecalibacterium prausnitzii) abundance, lipid profile and anthropometric parameters were evaluated at baseline and after twenty weeks of intervention.; Results: The energy-restricted diet significantly reduced body weight, BMI, fat mass, acetic and butyric acids, and improved the lipid profile (total cholesterol, low-density lipoprotein cholesterol, and triglycerides) of both groups. Changes in the molar ratio of SCFA towards the correct ratio were also observed. All the results were independent of Lactobacillus rhamnosus supplementation, with no significant differences between the two groups.; Conclusions: Twenty weeks of probiotic supplementation has no additional beneficial effects on selected gut bacteria abundance, SCFA levels, or lipid profile beyond the effect of an energy-restricted diet in overweight and obese women with PCOS.

Lagowska, K. and K. Kapczuk (2021). "Effects of nutritional intervention with or without metformin on insulin resistance in adolescents with polycystic ovary syndrome: a preliminary study." Progress in Nutrition 23(1): e2021015.
	The aim of the study is show whether, and to what extent, nutritional interventions with or without metformin that effectively result in weight reduction in obese adolescents with Polycystic Ovary Syndrome (PCOS) can help to alleviate insulin resistance. 35 obese adolescents with PCOS and insulin resistance were recruited to the study and they were randomly assigned to one of two subgroups: sixteen to a group given a nutritional intervention and metformin treatment (NM) and nineteen to a group given only nutritional intervention (NI). Body weight, body composition, energy and nutrients intake as well insulin and glucose levels were measured at the beginning of the study and after 8 weeks of the nutritional intervention. In both groups after 8 weeks of nutritional intervention the reduction in body weight and fat mass were observed. Fasting insulin concentrations measured after 8 weeks of NI were found to be significantly lower in the MN group. In group NI, the 8 weeks of intervention proved insufficient for the changes in fasting insulin concentrations. Longer term studies are needed to see if this therapy can result in sustained decreases in body weight and improvements in insulin resistance.

Lai, L., et al. (2023). "The efficacy of acceptance and commitment therapy for chronic pain: A three-level meta-analysis and a trial sequential analysis of randomized controlled trials." Behaviour Research and Therapy 165: 104308.
	The current study included randomized controlled trials (RCTs) to assess the benefits of Acceptance and commitment therapy (ACT) for chronic pain. Searches were conducted in Web of Science, PsycINFO, PubMed, Scopus, Cochrane Library, and Embase from inception until September 30, 2022. Thirty-three RCTs, including 2293 participants, were included. Small to medium effect sizes for pain intensity/physical function favoring ACT were found both at post-treatment (pain intensity: g = 0.44; physical function: g = 0.59) and follow-up (pain intensity: g = 0.34; physical function: g = 0.56). The effect sizes on psychological outcomes were significant at post-treatment (depression: g = 0.43; anxiety: g = 0.43; quality of life: g = 0.45) and follow-up (depression: g = 0.43; anxiety: g = 0.35; quality of life: g = 0.43). The results of the trial sequential analyses indicated that pooled estimates were unlikely to be incidental findings, as effects of multiple testing were controlled and power was adequate. Face-to-face ACT yielded significantly larger effects on physical outcomes than internet-delivered ACT. Participants with chronic headache and fibromyalgia showed greater benefit from ACT compared to those with non-specific pain or mixed pain. In addition, the longer the follow-up duration, the smaller the effect sizes for pain intensity/physical function at follow-up. The present meta-analysis suggests sufficient evidence for the significant benefits of ACT for people with chronic pain.Copyright © 2023 Elsevier Ltd

Lai, S., et al. (2020). "Sexual Functions in Women With Stress Urinary Incontinence After Mid-Urethral Sling Surgery: A Systematic Review and Meta-Analysis of Prospective Randomized and Non-Randomized Studies." The Journal of Sexual Medicine 17(10): 1956-1970.
	Background: Stress urinary incontinence (SUI) is a common, distressing health issue which affects many women. Mid-urethral sling (MUS) surgeries are recommended as gold standard interventions, although evidence regarding their impact on female sexual function remains controversial.; Aim: To provide high-quality evidence of the impact of MUS surgeries on sexual functions in women with SUI.; Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify studies assessing the effect of MUS treatments on sexual functions in women with SUI. The included studies were prospective randomized or non-randomized trials which assessed patients using 2 validated questionnaires, the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Pre- and postoperative data regarding sexual function were extracted. Meta-analysis of comparable data was performed using Review Manager (version 5.3) software.; Main Outcome Measures: The relationship between MUS interventions and sexual functions was analyzed by pooling weighted mean differences (WMD) with 95% CI from studies which used either the FSFI or PISQ-12 questionnaires, before and after receiving surgical interventions.; Results: Of the 22 eligible studies, 13 utilized FSFI and 9 adopted the PISQ-12. Pooled analysis indicates that 6-month postoperative PISQ-12 scores were significantly higher than preoperative scores (WMD -3.31 points; 95% CI -5.32 to -1.30; P = .001). Similar results were found at the 12-month juncture (WMD -3.30 points; 95% CI -6.01 to -0.58; P = .02) and at 24 months (WMD -4.44 points; 95% CI -5.45 to -3.44; P < .00001). Likewise, pooled postoperative FSFI total scores were significantly higher than preoperative scores at 6 months (WMD -2.22 points; 95% CI -3.36 to -1.08; P = .00001) and 12 months (WMD -3.49 points; 95% CI -5.96 to -1.02; P = .006). Postoperative FSFI sub-scores also suggest that desire, arousal, orgasm, lubrication, satisfaction, and pain during sexual intercourse significantly improved postoperatively (all P < .05). Moreover, combined evidence highlighted a significant reduction in coital incontinence postoperatively (risk ratio 5.78; 95% CI 3.16-10.58; P < .00001).; Clinical Implications: These assessment tools might be more appropriately used to create opportunities for counseling.; Strengths & Limitations: We encountered substantial heterogeneity and insufficient long term follow-up data. There is also a distinct lack of standards, in terms of data recording and reporting across this evidence base which adds to the problems with the PISQ-12 and FSFI which, even though validated, appear unsophisticated and not necessarily fit-for-purpose.; Conclusion: This meta-analysis confirms that sexual functions do improve after MUS surgeries for women with SUI. Lai S, Diao T, Zhang W, et al. Sexual Functions in Women With Stress Urinary Incontinence After Mid-Urethral Sling Surgery: A Systematic Review and Meta-Analysis of Prospective Randomized and Non-Randomized Studies. J Sex Med 2020;17:1956-1970. (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Lai, S., et al. (2024). "IVF versus IUI with ovarian stimulation for unexplained infertility: a collaborative individual participant data meta-analysis." Human Reproduction Update 30(2): 174-185.
	BACKGROUND: IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy. OBJECTIVE AND RATIONALE: Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility. SEARCH METHOD(S): We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool. OUTCOME(S): Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81-1.74, I2 1/4 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41-1.50, I2 1/4 0.0%). WIDER IMPLICATION(S): There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making.Copyright © 2024 Oxford University Press. All rights reserved.

Laios, A., et al. (2022). "Outcomes of ovarian transposition in cervical cancer; an updated meta-analysis." BMC Women's Health 22(1): 305.
	Background: Cervical cancer is the most common indication for ovarian transposition in reproductive-age women. Ovarian transposition should be performed in premenopausal women undergoing pelvic irradiation to preserve ovarian function, and prevent early menopause. As women become more knowledgeable about their fertility options, it is still unclear who will benefit from the intervention. We updated our previous meta-analysis of ovarian function preservation, symptomatic ovarian cysts, and metastases to the transposed ovaries following ovarian transposition in cervical cancer patients to further guide current clinical practice.; Methods: A systematic search of Medline, Embase, Web of Science, and The Cochrane Library databases, dating from January 1980 to July 2021, was conducted. We computed the summary proportions of women who had ovarian function preservation, non-ovarian cyst formation and metastases to the transposed ovaries following ovarian transposition by random-effects meta-analysis and we explored study heterogeneity by type of radiotherapy.; Results: There were 29 publications reporting on 1160 women with cervical cancer who underwent ovarian transposition. In the group that underwent surgery alone, 91% of the women had preserved ovarian function (95% CI 83-100), 89% (95% CI 80-99) of women who did not develop ovarian cysts, and 99% (95% CI 1-5) of women who did not suffer metastases to the transposed ovaries. In the surgery ± brachytherapy (BR) group, the proportion of women with the preserved ovarian function was 93% (95% CI 76-113), 84% (95% CI 69-103) of women who did not develop ovarian cysts, and 99% (95% CI 82-120) of women who did not suffer metastases to the transposed ovaries. In the external beam pelvic radiotherapy (EBRT) ± BR ± surgery group, the proportion of women with the preserved ovarian function was 61% (95% CI 55-69), and 95% (95% CI 85-107) of women who developed ovarian cysts. There were no metastases to the transposed ovaries in that group.; Conclusions: In women with cervical cancer, ovarian transposition offers a significant preservation of the ovarian function. Despite an expected incidence of ovarian cyst formation, it carries almost no risk for metastases to the transposed ovaries. (© 2022. The Author(s).)

Lakshmi Jada, N., et al. (2023). "Herbs as a Source for the Treatment of Polycystic Ovarian Syndrome: A Systematic Review." Biotech (Basel (Switzerland)) 12(1).
	Background: Polycystic ovarian syndrome (PCOS) is a neuroendocrine metabolic disorder characterized by an irregular menstrual cycle. Treatment for PCOS using synthetic drugs is effective. However, PCOS patients are attracted towards natural remedies due to the effective therapeutic outcomes with natural drugs and the limitations of allopathic medicines. In view of the significance of herbal remedies, herein, we discuss the role of different herbs in PCOS.; Methods: By referring to the Scopus, PubMed, Google Scholar, Crossref and Hinari databases, a thorough literature search was conducted and data mining was performed pertaining to the effectiveness of herbal remedies against PCOS.; Results: In this review, we discuss the significance of herbal remedies in the treatment of PCOS, and the chemical composition, mechanism of action and therapeutic application of selected herbal drugs against PCOS.; Conclusions: The present review will be an excellent resource for researchers working on understanding the role of herbal medicine in PCOS.

Lam Christine, M., et al. (2022). "Behavioral interventions for improving sleep outcomes in menopausal women: a systematic review and meta-analysis." Menopause (New York, N.Y.) 29(10): 1210-1221.
	Importance: Perimenopausal and postmenopausal women commonly report sleep disruption and insomnia. Behavioral interventions may be safe alternatives for patients who are unwilling to begin pharmacological treatments because of adverse effects, contraindications, or personal preference.; Objective: The primary objective is to assess the efficacy of behavioral interventions on sleep outcomes among perimenopausal and postmenopausal women, as measured using standardized scales and objective methods (polysomnography, actigraphy). The secondary objective is to evaluate the safety of these methods through occurrence of adverse events.; Evidence Review: Searches were performed within MEDLINE (OVID interface, 1946 onward), Embase (OVID interface, 1974 onward), Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science (Core collection) using a search strategy developed in consultation with a health sciences librarian. Title/abstract and full-text screenings were performed in duplicate, and relevant studies were selected based on inclusion and exclusion criteria set to identify randomized controlled trials evaluating the effects of behavioral interventions on sleep quality. Risk of bias assessments were done using the Cochrane Risk of Bias 2 tool, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of the body of evidence. Data were pooled in a meta-analysis using a random-effects model.; Findings: Nineteen articles reporting results from 16 randomized controlled trials were included, representing a total of 2,108 perimenopausal and postmenopausal women. Overall, behavioral interventions showed a statistically significant effect on sleep outcomes (standardized mean difference [SMD], -0.62; 95% confidence interval [CI], -0.88 to -0.35; I2 = 93.4%). Subgroup analyses revealed that cognitive behavioral therapy (SMD, -0.40; 95% CI, -0.70 to -0.11; I2 = 72.7%), physical exercise (SMD, -0.57; 95% CI, -0.94 to -0.21; I2 = 94.0%), and mindfulness/relaxation (SMD, -1.28; 95% CI, -2.20 to -0.37; I2 = 96.0%) improved sleep, as measured using both subjective (eg, Pittsburg Sleep Quality Index) and objective measures. Low-intensity (SMD, -0.91; 95% CI, -1.59 to -0.24; I2 = 96.8) and moderate-intensity exercise (SMD, -0.21; 95% CI, -0.34 to -0.08; I2 = 0.0%) also improved sleep outcomes. No serious adverse events were reported. Overall risk of bias ranged from some concern to serious, and the certainty of the body of evidence was assessed to be of very low quality.; Conclusions and Relevance: This meta-analysis provides evidence that behavioral interventions, specifically, cognitive behavioral therapy, physical exercise, and mindfulness/relaxation, are effective treatments for improving sleep outcomes among perimenopausal and postmenopausal women.; Competing Interests: Financial disclosure/conflicts of interest: Alison K. Shea has received honoraria from Pfizer and Bio-Syent and has received grant funding from Pfizer. The other authors have nothing to disclose. (Copyright © 2022 by The North American Menopause Society.)

Lam, N. S. K., et al. (2022). "The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review." Biomedicine and Pharmacotherapy 146: 112541.
	Objectives: To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. Method(s): A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605). Data sources: Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period. Result(s): We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated. Limitation(s): Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English. Conclusion(s): Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.Copyright © 2021 The Authors

Lamba, N., et al. (2019). "Fertility after transsphenoidal surgery in patients with prolactinomas: A meta-analysis." Clinical neurology and neurosurgery 176: 53-60.
	Pituitary prolactinomas in women often lead to amenorrhea, galactorrhea, or infertility. The purpose of this study was to evaluate the effectiveness of transsphenoidal surgery (TSS) in restoring fertility in women with proloactinomas. A systematic search of the literature was conducted in accordance with PRISMA guidelines through 6/13/2017. PubMed, Embase, and Cochrane databases were utilized to select studies reporting on patients with pituitary prolactinomas removed via TSS. Outcomes extracted included pre- and post-operative rates of menses, lactation, and fertility. Pooled effect estimates were calculated using random-effects. After removal of duplicates, 900 articles remained, of which 14 were meta-analyzed. The mean difference between pre- and post-operative prolactin level was 186.9 (95% CI = 133.7, 240.1; I 2 = 69.9%; P-heterogeneity<0.01; 7 studies). The pooled prevalence of pre-operative amenorrhea was 96% (95% CI = 92%, 98%; I 2 = 45.8%; P-heterogeneity = 0.09; 11 studies) and significantly larger than post-operative amenorrhea of 40% (95% CI = 27%, 55%; P- I 2 = 85%; heterogeneity<0.01; 11 studies); (P-interaction comparing the 2 groups <0.01). The pooled prevalence of pre-operative galactorrhea was 84% (95% CI = 74%, 90%; I 2 = 66.9%; P-heterogeneity<0.01; 10 studies) and significantly larger than post-operative galactorrhea of 29% (95% CI = 17%, 44%; I 2 = 76.5%; P-heterogeneity<0.01; 7 studies) (P-interaction<0.01). Univariate meta-regression on age, continent, publication year, study design, quality, duration, or timing revealed these covariates were not effect modifiers for any of the 3 outcomes (all P > 0.05). No evidence of publication bias was seen using Begg's and Egger's tests (all P > 0.05). Transsphenoidal surgery appeared to improve fertility measures in women with pituitary prolactinomas. (Copyright © 2018. Published by Elsevier B.V.)

Lamore, K., et al. (2019). "Return to work interventions for cancer survivors: A systematic review and a methodological critique." International Journal of Environmental Research and Public Health 16(8): 1343.
	Cancer patients are more at risk of being unemployed or having difficulties to return to work (RTW) compared to individuals without health concerns, and is thus a major public health issue. The aim of this systematic review is to identify and describe the interventions developed specifically to help cancer patients to RTW after treatment. Two researchers independently screened the articles for inclusion and Critical Appraisal Skills Program (CASP) checklists were used to assess the methodology of the included studies. Ten manuscripts met the inclusion criteria. The type of studies were three quasi-experimental studies, three longitudinal studies, three randomized controlled trials (RCTs) and a qualitative study. RTW interventions were conducted in or outside the hospital (n = 6 and 3 respectively), or both (n = 1). Improvements in RTW were only observed in quasi-experimental studies. No improvement in RTW was noted in RCTs, nor in other measures (e.g., quality of life, fatigue). Lack of statistically significant improvement does not necessarily reflect reality, but may be attributed to non-adapted research methods. This systematic review underscores the need for researches in the RTW field to reach a consensus on RTW criteria and their assessment. Recommendations to this effect are suggested.Copyright © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Lancellotta, V., et al. (2020). "The role of vaginal brachytherapy in stage I endometrial serous cancer: a systematic review." Journal of Contemporary Brachytherapy 12(1): 61-66.
	Purpose: Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT).; Material and Methods: A systematic research using PubMed, Scopus, and Cochrane library was conducted to identify full articles evaluating the efficacy of VBT in patients with stage I USC. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials, and in PROSPERO for searching ongoing or recently completed systematic reviews.; Results: All studies were retrospective and 364 of evaluated patients were found. The average local control was 97.5% (range, 91-100%), the disease free-survival was 88% (range, 82-94%), the overall survival was 93% (range, 72-100%), the specific cancer survival was 89.4% (range, 84.8-94%), and the G3-G4 toxicity was 0-8%.; Conclusions: These data support the concept that in adequately selected patients, VBT alone may be a suitable radiotherapy technique in women with stage I USC who underwent surgical staging and received adjuvant chemotherapy.; Competing Interests: The authors report no conflict of interest. (Copyright © 2020 Termedia.)

Lancellotta, V., et al. (2021). "The role of brachytherapy (interventional radiotherapy) for primary and/or recurrent vulvar cancer: a Gemelli Vul.Can multidisciplinary team systematic review." Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 23(8): 1611-1619.
	Objective: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma.; Evidence Acquisition: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990-2018) as concerns the years of the publication was considered.; Evidence Synthesis: Primary disease: the median 5-year LC was 43.5% (range 19-68%); the median 5-year DFS was 44.5% (range 44-81%); the median 5-year OS was 50.5% (range 27-85%). Recurrent disease: the median 5-year DFS was 64% (range 56-72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3-4) ranged from 0% to 14.3% (median 7.7%).; Conclusion: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Landen Charles, N., et al. (2023). "Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial." Clinical cancer research : an official journal of the American Association for Cancer Research 29(9): 1698-1707.
	Purpose: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.; Patients and Methods: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations between progression-free survival (PFS) and genomic biomarkers were evaluated using standard correlation analyses and log-rank of Kaplan-Meier estimates.; Results: Among biomarker-evaluable samples, 22% (234/1,050) harbored BRCA1/2 mutations and 46% (446/980) were HRD. Median TMB was low irrespective of BRCA1/2 or HRD. Only 3% (29/1,024) had TMB ≥10 mut/Mb, and 0.3% (3/1,022) were MSI-high. PFS was better in BRCA2-mutated versus BRCA2-non-mutated tumors and in HRD versus proficient tumors. PD-L1 positivity (≥1% expression on ICs) was associated with HRD but not BRCA1/2 mutations. PFS was not improved by adding atezolizumab in BRCA2-mutated or HRD tumors; there was a trend toward enhanced PFS with atezolizumab in BRCA1-mutated tumors.; Conclusions: Most ovarian tumors have low TMB despite BRCA1/2 mutations or HRD. Neither BRCA1/2 mutation nor HRD predicted enhanced benefit from atezolizumab. This is the first randomized double-blind trial in ovarian cancer demonstrating that genomic instability triggered by BRCA1/2 mutation or HRD is not associated with improved sensitivity to immune checkpoint inhibitors. See related commentary by Al-Rawi et al., p. 1645. (©2023 The Authors; Published by the American Association for Cancer Research.)

Lane, G. I., et al. (2020). "Vaginal lasers for treating stress urinary incontinence in women." Cochrane Database of Systematic Reviews 2020(6): CD013643.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects of vaginal lasers for treating stress urinary incontinence in women; and summarise the principal findings of relevant economic evaluations.Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Lane, G. I., et al. (2021). "Vaginal lasers for treatment stress urinary incontinence in women: A cochrane systematic review and meta-analysis." Neurourol. Urodyn. 40(SUPPL 1): S70-S72.
	
Lang, N., et al. (2023). "Nab-PIPAC: a phase IB study protocol of intraperitoneal cisplatin and nab-paclitaxel administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of advanced malignancies confined to the peritoneal cavity." BMJ Open 13(1): e067691.
	Introduction: Intraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects.; Methods and Analysis: Nab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m 2 ) and cisplatin (10.5 mg/m 2 ) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4-6 weeks intervals for three courses total.A total of 6-36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data.; Ethic and Dissemination: Ethical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings.; Trial Registration Number: NCT04000906.; Competing Interests: Competing interests: None declared for IL-G, FR, MU, AD, PP, CT, MDM and NM. MH declares the following competing interests: ENCARE Consultant fee (institution); Nestlé; Research funding Capnomed Sponsoring of scientific meetings MSD; Fresenius Speaker honorary (institution); ERAS society Board member, chair education; ISSPP Board member, chair education. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lang Susan, M. and O. Dorigo (2022). "Cell-based immunotherapies in gynecologic cancers." Current opinion in obstetrics & gynecology 34(1): 10-14.
	Purpose of Review: This review provides an update on recent developments in cell-based immunotherapy in gynecologic cancers.; Recent Findings: Chimeric antigen receptor (CAR) technology has made significant progress allowing now for not only expressing CARs on T-cells, but also on other immune effector cells, such as natural killer cells and macrophages. Cell-based vaccines have started to show promising results in clinical trials.; Summary: Cell-based immunotherapies in gynecologic cancers continue to evolve with promising clinical efficacy in select patients. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Lanier, C. and C. Melton Tyler (2023). "Oteseconazole for the Treatment of Recurrent Vulvovaginal Candidiasis: A Drug Review." The Annals of Pharmacotherapy: 10600280231195649.
	Objective: The objective of the study is to describe and analyze the pharmacodynamics and pharmacokinetics of oteseconazole as well as the clinical evidence supporting the efficacy of oteseconazole in treating recurrent vulvovaginal candidiasis (RVVC).; Data Sources: A literature search was conducted using MEDLINE and EMBASE databases (2015-June 2023). Search terms included "oteseconazole" OR "VT-1161" or "VIVJOA" AND "RVVC" or "recurrent vulvovaginal candidiasis" or "vulvovaginal candidiasis." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review.; Study Selection and Data Extraction: Relevant studies in English and clinical trials conducted in humans were reviewed.; Data Synthesis: Oteseconazole is approved for the treatment of RVVC. In 2 identical phase III studies, oteseconazole was superior to placebo through 48 weeks for preventing recurrence of RVVC (6.7% vs 42.8%, P < 0.001 and 3.9% vs 39.4%, P < 0.001). In the only phase III trial comparing oteseconazole against active drug, oteseconazole was well tolerated and exhibited noninferiority to fluconazole in acute treatment and superiority to placebo for prevention maintenance through 50 weeks (5.1% vs 42.2%, P < 0.001).; Relevance to Patient Care and Clinical Practice in Comparison to Existing Agents: This review describes the use of oteseconazole for the treatment of RVVC as compared with fluconazole. Oteseconazole is an effective treatment option for common pathogens causing vulvovaginal candidiasis, including Candida and fluconazole-resistant Candida .; Conclusions: Oteseconazole is an effective and safe treatment option for the management of RVVC though current research lacks comparison with established maintenance regimens. Additional research is needed to ascertain the placement of oteseconazole in the treatment of RVVC.; Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lara, D., et al. (2022). "Do knowledge and verbal instructions improve the contractile capacity/ability of the pelvic floor muscles in healthy women? A systematic review."
	
Larouche, M., et al. (2021). "Surgical Management of Symptomatic Apical Pelvic Organ Prolapse: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 137(6): 1061-1073.
	Objective: To systematically review objective and subjective success and complications of apical suspensions for symptomatic uterine or vaginal vault pelvic organ prolapse (POP).; Data Sources: MEDLINE, CENTRAL, ClinicalTrials.gov, and EMBASE (2002-2019) were searched using multiple terms for apical POP surgeries, including comparative studies in French and English.; Methods of Study Selection: From 2,665 records, we included randomized controlled trials and comparative studies of interventions with or without hysterectomy, including abdominal apical reconstruction through open, laparoscopic, or robotic approaches and vaginal apical reconstructions. Repairs using transvaginal mesh, off-the-market products, procedures without apical suspension, and follow-up less than 6 months were excluded.; Tabulation, Integration, and Results: Relative risk (RR) was used to estimate the effect of surgical procedure on each outcome. For each outcome and comparison, a meta-analysis was conducted to pool the RRs when possible. Meta-regression and bias tests were performed when appropriate. The GRADE (Grades for Recommendation, Assessment, Development and Evaluation) system for quality rating and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting were used. Sixty-two articles were included in the review (N=22,792) and 50 studies in the meta-analyses. There was heterogeneity in study quality, techniques used, and outcomes reported. Median follow-up was 1-5 years. Vaginal suspensions showed higher risk of overall and apical anatomic recurrence compared with sacrocolpopexy (RR 1.82, 95% CI 1.22-2.74 and RR 2.70, 95% CI 1.33-5.50) (moderate), whereas minimally invasive sacrocolpopexy showed less overall and posterior anatomic recurrence compared with open sacrocolpopexy (RR 0.59, 95% CI 0.47-0.75 and RR 0.59, 95% CI 0.44-0.80, respectively) (low). Different vaginal approaches, and hysterectomy and suspension compared with hysteropexy had similar anatomic success. Subjective POP recurrence, reintervention for POP recurrence and complications were similar between most procedures.; Conclusion: Despite variations in anatomic outcomes, subjective outcomes and complications were similar for apical POP procedures at 1-5 years. Standardization of outcome reporting and comparative studies with longer follow-up are urgently needed.; Systematic Review Registration: PROSPERO, CRD42019133869.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Larsen Mads, S., et al. (2023). "Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial." The Journal of nutrition 153(11): 3173-3184.
	Background: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations.; Objective: To determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise.; Design: Forty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring- 13 C 6 ] phenylalanine tracer infusion with the collection of bilateral muscle biopsies.; Results: Myofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744).; Conclusion: A 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program.; Trial Registry: clinicaltrials.gov (ID: NCT03326284). (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Lassche, G., et al. (2019). "Whole-body hyperthermia in combination with systemic therapy in advanced solid malignancies." Critical Reviews in Oncology/Hematology 139: 67-74.
	Whole-body hyperthermia (WBH)might be beneficial for patients with metastasized solid malignancies when combined with systemic therapy. This review identified and summarized the phase I/II studies (n = 13/14)conducted using this combination of therapies. Most of the phase II studies used radiant heating methods in a thermal dose of 41.8 degreeC (1 h). All studies used classic chemotherapy. Great inter-study heterogeneity was observed regarding treatment regimes, included patients and reported response rates (12-89%). Ovarian cancer, colorectal adenocarcinoma, lung cancer and sarcoma have been studied most. Most reported toxicity (grade 3/4)was myelosuppression. Treatment related mortality was present (4 patients)in three out 14 phase II studies (350 evaluable patients, over 966 cycles of WBH with chemotherapy). Absence of phase III trials makes the additive value of WBH highly speculative. As modern oncology offers many less invasive treatments options, it is unlikely WBH will ever find its way in routine clinical care.Copyright © 2019 Elsevier B.V.

Lau, H.-H., et al. (2023). "FIGO recommendations: Use of midurethral slings for the treatment of stress urinary incontinence." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 161(2): 367-385.
	Background: Stress urinary incontinence (SUI) is a global problem. It can significantly adversely impact a woman's quality of life. The use of synthetic mesh in vaginal surgery is controversial, especially when used for pelvic organ prolapse surgery. Although negative effects have been reported, the synthetic mesh midurethral sling (MUS) is considered to be safe and effective in the surgical treatment of SUI.; Objectives: To provide evidence-based data and recommendations for the obstetrician/gynecologist who treats women with SUI and performs or plans to perform MUS procedures.; Methods: Academic searches of MEDLINE, the Cochrane Library, Embase, and Google Scholar articles published between 1987 and March 2020 were performed by a subgroup of the Urogynecology and Pelvic Floor Committee, International Federation of Gynecology and Obstetrics (FIGO).; Selection Criteria: The obtained scientific data were associated with a level of evidence according to the Oxford University Centre for Evidence-Based Medicine and GRADE Working Group system. In the absence of concrete scientific evidence, the recommendations were made via professional consensus.; Results: The FIGO Urogynecology and Pelvic Floor Committee reviewed the literature and prepared this evidence-based recommendations document for the use of MUS for women with SUI.; Conclusions: Despite the extensive literature, there is a lack of consensus in the optimal surgical treatment of SUI. These recommendations provide a direction for surgeons to make appropriate decisions regarding management of SUI. The MUS is considered safe and effective in the treatment of SUI, based on many high-quality scientific publications and professional society recommendations. Comprehensive long-term data and systemic reviews are still needed, and these data will become increasingly important as women live longer. These recommendations will be continuously updated through future literature reviews. (© 2023 International Federation of Gynecology and Obstetrics.)

Lau, Y., et al. (2021). "Effectiveness of digital psychotherapeutic intervention among perinatal women: A systematic review and meta-analysis of randomized controlled trials." World journal of psychiatry 11(4): 133-152.
	BACKGROUND: The perinatal period is a challenging time of substantial emotional, physiological, social, and relational changes. Depression, anxiety, and stress symptoms are common, and co-exist in the perinatal period. Digital technology continues to grow at an unprecedented pace with wide application, including psychotherapeutic intervention. A growing number of meta-analyses supported the application of digital psychotherapeutic intervention across different populations, but relatively few meta- and meta-regression analyses have concentrated on perinatal women. AIM: To evaluate the effectiveness of digital psychotherapeutic intervention on improving psychological outcomes among perinatal women and identify its essential features. METHODS: Randomized controlled trials (RCTs) were obtained from eight databases, including Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, Scopus, PsycINFO, PubMed, Web of Science, and ProQuest Dissertation and Theses from inception up until November 24, 2020. Comprehensive Meta-analysis 3.0 software was used to conduct meta- and meta-regression analyses. The Cochrane risk-of-bias tool and the Grading of the Recommendation, Assessment, Development, and Evaluation system were adopted to assess the individual and overall qualities of the evidence, respectively. RESULTS: A total of 25 RCTs that included 3239 women were identified. Meta-analyses revealed that intervention significantly improved depression (Hedges's g = 0.49), anxiety (g = 0.25), and stress (g = 0.47) symptoms compared to the control. Subgroup analyses demonstrated that a website platform with ≥ eight therapist-guided sessions using the theoretical principle of cognitive behavioral therapy was more effective than other treatments in improving depression symptoms in postnatal women. Meta-regression analyses observed that the age of perinatal women and the type of psychotherapy also had statistically significant effects on depression symptoms. Egger's regression asymmetry tests suggested that no publication biases occurred, but the overall quality of the evidence was very low. CONCLUSION: This review suggests that digital psychotherapeutic intervention may be a potential solution to reduce psychological problems in perinatal women. Further high-quality RCTs with large sample sizes are needed.

Lau, Y., et al. (2022). "Effect of digital cognitive behavioral therapy on psychological symptoms among perinatal women in high income-countries: A systematic review and meta-regression." Journal of Psychiatric Research 146: 234-248.
	Several reviews focused on the use of digital cognitive behavioral therapy (CBT) across different populations. This review synthesized randomized controlled trials (RCTs) that evaluated the effectiveness of digital CBT on psychological symptoms (depression, anxiety, and stress symptoms). An extensive search was conducted in 10 databases from inception until August 29, 2021. A meta-analysis using a random-effects model was performed using Hedges' g. The potential sources of heterogeneity were explored through subgroup analyses and meta-regression analysis. A total of 18 RCTs in 2514 perinatal women were identified from over 23 countries. The sample size ranged from 25 to 910. Meta-analyses showed that digital CBT significantly reduced depression (g = -0.56, 95% CI: -0.85, -0.27, I2 = 84.81%, p < 0.001), anxiety (g = -0.30, 95% CI: -0.44, -0.17, I2 = 0%, p < 0.001), and stress (g = -0.75, 95% CI: -0.95, -0.56, I2 = 0%, p < 0.001) symptoms at post-intervention and stress symptoms at follow-up (g = -0.52, 95% CI: -0.93, -0.11, I2 = 0%, p = 0.01) compared with those in the control group. Subgroup analyses highlighted that the intervention was effective when CBT was combined with other therapeutic components which delivered via a mobile application. Preferable features of intervention should be more than eight sessions and conducted for than 6 weeks among postnatal women. Multivariable meta-regression showed that age was a significant covariate on depression symptoms. The sample size in the selected RCTs was small, and the overall quality of the evidence was very low. Digital CBT is a potential intervention for alleviating psychological outcomes in perinatal women. This review suggests the essential features to optimize the intervention effect. Further well-designed RCTs with large sample sizes are necessary.Copyright © 2021 Elsevier Ltd

Laube, R., et al. (2021). "Assisted Reproductive Technology in Crohn's Disease and Ulcerative Colitis: A Systematic Review and Meta-Analysis." The American journal of gastroenterology 116(12): 2334-2344.
	Introduction: Infertility may occur in women with Crohn's disease (CD) and ulcerative colitis (UC), especially after surgery such as ileal pouch-anal anastomosis (IPAA). Assisted reproductive technology (ART) may be an option, but the safety and efficacy in this setting has been based on small cohorts to date. We performed a systematic review and meta-analysis to address this data gap.; Methods: A systematic review and random-effects meta-analysis was performed until May 2020. The primary outcomes were pregnancy and live birth rates per cycle of ART.; Results: Eleven studies met inclusion criteria for the systematic review and 4 for the meta-analysis. Compared with the general population, women with CD (with and without previous surgery) had no difference in pregnancy rates (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.45-1.05) but had reduced live births (OR = 0.67, 95% CI: 0.53-0.85) per cycle of ART. ART live birth rates are not reduced in women with medically managed CD; however, they are 49%-71% lower after CD-related surgery. Women with UC had no difference in both pregnancy rates (OR = 0.99, 95% CI: 0.63-1.55) and live birth rates (OR = 0.88, 95% CI: 0.67-1.17); however, live birth rates were reduced after IPAA failure (hazard ratio = 0.36, 95% CI: 0.14-0.92). Two studies did not identify any significant safety signals.; Discussion: ART is safe and effective in patients with UC and medically managed CD, with pregnancy and live birth rates similar to that of the general population. However, within the limitations of the available literature, current data suggest that efficacy is reduced in women with CD-related surgery and IPAA failure. Greater gastroenterologist awareness of ART is needed to facilitate timely fertility therapy referral when indicated, particularly in CD. (Copyright © 2021 by The American College of Gastroenterology.)

Laughlin-Tommaso Shannon, K., et al. (2022). "Uterine and Fibroid Imaging Analysis from the FIRSTT Study." Journal of women's health (2002) 31(4): 546-554.
	Background: Women with uterine fibroids often seek uterine-preserving treatments, rather than hysterectomy. Imaging-defined endpoints following nonsurgical treatments for fibroids are limited. Materials and Methods: Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT), a randomized controlled trial of uterine artery embolization (UAE) versus magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS), enrolled premenopausal women with symptomatic uterine fibroids. In this subanalysis, we report imaging results up to 36 months after UAE or MRgFUS. Magnetic resonance imaging (MRI) was performed at baseline for all women and during the 36 months after treatment if they did not meet other study endpoints. The main outcome of this subanalysis was fibroid volume reduction (defined both in terms of total fibroid load and volume of the largest fibroid), uterine volume reduction, and nonperfused volume. Results: During 2010-2014, 25 of the 37 women who were randomized and treated at Mayo Clinic had a 24-month follow-up MRI (11 UAE; 14 MRgFUS); among these women, 15 (7 UAE and 8 MRgFUS) had a 36-month follow-up MRI. Average age for the cohort was 44.1 (standard deviation, SD = 4.4) years. Nine patients had a second fibroid procedure by 36 months (seven in the MRgFUS arm and two in UAE arm). Median total fibroid load reduction was ∼50% in both treatment arms at both 24- and 36-month follow-up. Volume of the largest fibroid decreased more in the MRgFUS arm, whereas uterine volume decreased more in the UAE arm (neither reached statistical significance). At 24 months, median nonperfused volume was higher in the UAE arm (92%) than the MRgFUS arm (10%). Conclusions: Similar fibroid volume reduction was seen for the MRgFUS and UAE treatments in this comparative effectiveness study. Nonperfused volume 24 months after the procedure was higher in the UAE arm than in the MRgFUS arm. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov.

Laura, C., et al. (2023). "The effect of soy isoflavones on estrogen-related intermediate outcomes: A systematic review and meta-analysis of randomized controlled trials."
	
Laura, E., et al. (2023). "Comparative efficacy and reproductive outcomes after fertility-sparing treatment for endometrial hyperplasia, complex atypical hyperplasia, and early endometrial cancer: systematic review and network meta-analysis."
	
Laura, F. and H. Emma (2021). "Biopsychosocial interventions in body image and pain management in endometriosis: a systematic review." PROSPERO International prospective register of systematic reviews.
	
Laura, L.-L., et al. (2023). "Electrical stimulation in the treatment of genito-pelvic pain penetration disorders."
	
Laura, P., et al. (2022). "Impact of PGT on successful clinical pregnancy rates: a systematic review and meta- analysis."
	
Laura, P. and I. Sapiyat (2021). "Efficacy of laser vaporization compared with other surgical techniques in women with ovarian endometrioma: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Lauren, H., et al. (2021). "Does stigma relate to poor outcomes in chronic pain? A systematic review and narrative synthesis."
	
Lautz Timothy, B., et al. (2023). "Local treatment of rhabdomyosarcoma of the female genital tract: Expert consensus from the Children's Oncology Group, the European Soft-Tissue Sarcoma Group, and the Cooperative Weichteilsarkom Studiengruppe." Pediatric blood & cancer 70(5): e28601.
	The International Soft-Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft-tissue sarcoma cooperative groups (Children's Oncology Group, European Pediatric Soft-Tissue Sarcoma Group, and Cooperative Weichteilsarkom Studiengruppe). Besides other tasks, a major goal of INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long-term follow-up, and fertility preservation. Therefore, a review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results were that the prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. In conclusion, for the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment of these patients in different study groups. (© 2020 Wiley Periodicals LLC.)

Lavikainen Lauri, I., et al. (2023). "Risk of thrombosis and bleeding in gynecologic cancer surgery: systematic review and meta-analysis." American Journal of Obstetrics and Gynecology.
	Objective: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery.; Data Sources: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice.; Study Eligibility Criteria: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L.; Methods: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty.; Results: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures.; Conclusion: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Lazaridis, A., et al. (2022). "Nonsurgical management of adenomyosis: an overview of current evidence." Current opinion in obstetrics & gynecology 34(5): 315-323.
	Purpose of Review: Adenomyosis is a condition where endometrium-like tissue spreads within the myometrium. Although its prevalence in the general population is not exactly known, its clinical manifestations are well established and include pelvic pain, dysmenorrhea (painful periods), heavy menstrual bleeding and subfertility [1] . Adenomyosis often coexists with other gynaecological conditions, such as endometriosis or fibroids, and may cloud the clinical presentation [2] . The aim of this article is to review current noninterventional, nonsurgical management modalities and wherever possible offer information that allows women to make safe and informed choices regarding their treatment options.; Recent Findings: Recent studies support that medical strategies, including the Mirena coil, Dienogest and GnRH antagonists, are efficient in improving adenomyosis-associated symptoms. High-quality evidence is scarce and is needed to properly counsel women with this condition. Future research should prioritize overall pain, menstrual bleeding, quality of life and live birth as primary outcomes and assess women with different grades of adenomyosis.; Summary: This review provides the most current evidence with regards to the nonsurgical management of adenomyosis. In light of the paucity and low quality of existing data, high-quality trials are needed to definitely determine the impact of conservative and medical treatment on the clinical management of adenomyosis. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Lazzarin, S., et al. (2022). "Treatment of first trimester miscarriage: a prospective cohort study in a large tertiary care center in Northern Italy." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(1): 110-115.
	Objective: To assess acceptability, efficacy, and short- and medium-term complications of vaginal misoprostol therapy for the treatment of first trimester miscarriage.; Study Design: A prospective cohort study including women admitted to the Unit of Obstetrics, MBBM Foundation, San Gerardo Hospital (Monza, Italy) for medical or surgical treatment of first trimester miscarriage between October 2014 and March 2018. As per Institutional protocol, patients in the medical therapy group received 800 µg of misoprostol vaginally. A second dose could be considered 3 days after the first administration if that was ineffective. Surgical treatment consisted of uterine vacuum aspiration. Success of misoprostol treatment was defined as the expulsion of the gestational sac with no need for subsequent surgery.; Results: During the study period, 967 patients were diagnosed with first trimester miscarriage and were included in the study. Of these, 514 (53.2%) women were eligible for and consented to medical therapy. Surgical treatment was performed in the remaining 453 (46.8%) patients due to either medical contraindication to misoprostol or patient's choice. Acceptance of misoprostol as first therapeutic choice increased over time, becoming the preferred treatment after approximately 18 months of use in clinical practice. One dose of misoprostol was successful in 69.8% ( n = 359) of patients, whereas 20 women required urgent surgery for bleeding ( n = 19) or suspected infection ( n = 1). Among the remaining 135 patients, 20 (14.8%) refused the second dose of misoprostol and opted for surgery. Expulsion of the gestational sac was obtained in 74 additional cases who completed the medical protocol, for an overall success rate of 87.7% (433/494). The majority of women receiving misoprostol did not experience any short-term complication (92.0%) or side effect (93.8%). Eight (1.6%) cases requiring delayed surgery (hysteroscopy or vacuum aspiration) for retained product of conception were identified at the postmedical treatment follow up, thus leading to an actual success rate of misoprostol of 86.0% ( n = 425).; Conclusions: This is the first study assessing the acceptability, efficacy, and complication rate of medical management of first trimester miscarriage in an Italian tertiary care center. Our results confirm that misoprostol alone is an effective as well as a safe therapeutic option for the treatment of first trimester miscarriage.

Leary, A., et al. (2023). "Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours." European journal of cancer (Oxford, England : 1990) 192: 113259.
	Background: Lurbinectedin was approved by FDA and other health regulatory agencies for treating adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Safety profile at approved dose (3.2 mg/m 2 every 3 weeks) was acceptable and manageable in 105 adult SCLC patients from a phase II basket trial. This study analyses safety data from several solid tumours treated at the lurbinectedin-approved dose.; Methods: Data were pooled from 554 patients: 335 from all nine tumour-specific cohorts of the phase II basket trial and 219 from a randomised phase III trial (CORAIL) in platinum-resistant ovarian cancer. Events and laboratory abnormalities were graded using NCI-CTCAE v.4.; Results: Most common tumours were ovarian (n = 219, 40%), SCLC (n = 105, 19%) and endometrial (n = 73, 13%). Transient haematological laboratory abnormalities were the most frequent grade 3 or more events: neutropenia (41%), leukopenia (30%), anaemia (17%) and thrombocytopenia (10%). Most common treatment-emergent non-haematological events (any grade) were transient transaminase increases (alanine aminotransferase [66%], aspartate aminotransferase [53%]), fatigue (63%), nausea (57%), constipation (32%), vomiting (30%) and decreased appetite (25%). Dose reductions were mostly due to haematological toxicities, but most patients (79%) remained on full lurbinectedin dose. Serious events mostly consisted of haematological disorders. Eighteen treatment discontinuations (3%) and seven deaths (1%) were due to treatment-related events.; Conclusions: This analysis confirms a manageable safety profile for lurbinectedin in patients with advanced solid tumours. Findings are consistent with those reported in patients with relapsed SCLC, Ewing sarcoma, germline BRCA1/2 metastatic breast cancer, neuroendocrine tumours and ovarian cancer.; Competing Interests: Declaration of Competing Interest Vivek Subbiah reports research funding from Pharma Mar and Jazz Pharma to conduct clinical trials; other grant support for clinical trials from AbbVie; Agensys, Inc; Alfasigma; Altum; Amgen; Bayer; BERG Health; Blueprint Medicines Corporation; Boston Biomedical, Inc; Boston Pharmaceuticals; Celgene Corporation; D3 Bio, Inc; Dragonfly Therapeutics, Inc; Exelixis; Fujifilm; GlaxoSmithKline; Idera Pharmaceuticals, Inc; Incyte Corporation; Inhibrx; Loxo Oncology/ Eli Lilly; MedImmune; MultiVir, Inc; Novartis; NanoCarrier, Co; National Comprehensive Cancer Network; NCI-CTEP; Novartis; PharmaMar; Pfizer; Relay Therapeutics; Roche/Genentech; Takeda; Turning Point Therapeutics; UT MD Anderson Cancer Center; and Vegenics Pty Ltd; travel support from ASCO, ESMO, Helsinn Healthcare, Incyte Corporation, Novartis and PharmaMar; consultancy or advisory board participation for Helsinn Healthcare, Incyte Corporation, Loxo Oncology/Eli Lilly, MedImmune, Novartis, QED Therapeutics, Relay Therapeutics, Daiichi-Sankyo and R-Pharm US; and other relationship with Medscape. Cristian Fernandez, Carmen Kahatt, Antonio Nieto and Ali Zeaiter are full-time employees of and own stock from Pharma Mar. Martin Cullell-Young is a full-time employee of Pharma Mar. All other authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ledee, N., et al. (2023). "Pre-conceptional Endometrial Immune Profiling: a Personalized Approach to improve pregnancy Rates in Good Prognosis IVF/ICSI Patients - Preliminary Results of a Randomized Controlled Study."  159.
	Introduction: Endometrial immune profiling aims to identify immune disturbances that may be contributing to infertility or pregnancy loss and guide the development of personalized treatment plans. Previous extended cohort studies suggested an benefit for women who have experienced recurrent pregnancy losses or implantation failures. This study aims to investigate the impact of personalized care in patients with immune deregulation on pregnancy rates in good prognosis IVF/ICSI patients. Materials and Methods: A randomized controlled trial was conducted on 491 infertile patients starting their course of assisted reproductive treatment between October 2015 and February 2023. Endometrial samples were collected during the mid‐luteal phase, and mRNA expression of five key‐selected immune biomarkers was evaluated by RT‐qPCR before embryo transfer. Patients with a diagnosed deregulation were randomized with half receiving conventional standard treatment and the other half personalized treatment for their subsequent embryo transfer. Results: Among 483 patients analyzed, 22% had a regulated profile, while 78% had immune deregulation. Among deregulated patients, 189 received conventional treatment, and 187 received personalized treatment based on their deregulation. Ongoing pregnancy rates per embryo transfer were compared among patients in the conventional, personalized, and non‐deregulated groups. Follow‐up is ongoing, but preliminary results suggest an impact of immune deregulation on subsequent pregnancy rates. Conclusion: This study highlights the potential of endometrial immune profiling as a promising tool for enhancing medical performance in IVF/ICSI patients, reducing time and cost to a successful pregnancy. The uterine immune environment should be considered as one piece of the puzzle in assisted reproductive medicine.

Ledermann, J. A., et al. (2021). "Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial." ESMO Open 6(2): 100043.
	BACKGROUND: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS). PATIENTS AND METHODS: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance). Due to an enforced redesign of the trial in September 2011, the primary endpoint became PFS between arms A and C which we have previously published, and the overall survival (OS) was defined as a secondary endpoint, which is reported here. RESULTS: After a median follow-up of 25.6 months, strong evidence of an effect of concurrent plus maintenance cediranib on PFS was observed [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.72, P < 0.0001]. In this final update of the survival analysis, 90% of patients have died. There was a 7.4-month difference in median survival and an HR of 0.86 (95% CI: 0.67-1.11, P = 0.24) in favour of arm C. There was strong evidence of a departure from the assumption of non-proportionality using the Grambsch-Therneau test (P = 0.0031), making the HR difficult to interpret. Consequently, the restricted mean survival time (RMST) was used and the estimated difference over 6 years by the RMST was 4.8 months (95% CI: -0.09 to 9.74 months). CONCLUSIONS: Although a statistically significant difference in time to progression was seen, the enforced curtailment in recruitment meant that the secondary analysis of OS was underpowered. The relative reduction in the risk of death of 14% risk of death was not conventionally statistically significant, but this improvement and the increase in the mean survival time in this analysis suggest that cediranib may have worthwhile activity in the treatment of recurrent ovarian cancer and that further research should be undertaken.

Ledermann, J. A., et al. (2022). "Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study." ESMO Open 7(1): 100311.
	Background: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer.; Patients and Methods: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics.; Results: Overall, 216 patients were randomized to gatipotuzumab (n = 151) or placebo (n = 65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P = 0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events.; Conclusions: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.; Trial Registration: ClinicalTrials.govNCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599.; Competing Interests: Disclosure JL reports institutional research grant from AstraZeneca and MSD/Merck; serves on the steering group and advisory board of Pfizer; serves on the advisory board and provides lectures for AstraZeneca, Artios Pharma; GSK, MSD, Clovis Oncology, Eisai, and Neopharm; is a VBL Therapeutics Chair; is on the IDMC for Regeneron; is the Vice President of ESGO; and an editor of the ESMO Gynaecological Clinical Practice Guidelines; FR reports honoraria from GSK and MSD; is on the speakers bureau for GSK and MSD; reports travel, accommodations, expenses paid by GSK, MSD, and PharmaMar. UDG reports consultant fees from Janssen, Astellas Pharma, Sanofi, Bayer, Pfizer, BMS, Novartis, Ipsen, and Merck. JAA reports honoraria from Astellas Pharma and Pfizer; consulting or advisory role for Pfizer, Astellas Pharma, Janssen-Cilag, MSD, Bristol-Myers Squibb, EUSA Pharma, Merck, and AstraZeneca; and research funding from Bristol-Myers Squibb (institution); MRM reports grants from GSK, Pfizer, AstraZeneca, and Clovis; CC is on the advisory boards of Boehringer Ingelheim, Novartis, Pfizer, and Merck; reports lecture fees from AstraZeneca, BMS, Bayer, Ipsen, Astellas, MSD, and Sandoz; reports travel grants from Alvogen, Merck, and Boehringer Ingelheim; and reports educational grants from AstraZeneca. ACH reports grants or contracts from PharmaMar, AstraZeneca, Lilly, Eisai, and Tesaro/GSK; reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, PharmaMar, AstraZeneca, Lilly, Tesaro/GSK, and Deciphera; reports support for attending meetings and/or travel from PharmaMar, Roche, Lilly, GSK/Tesaro, and Merck; and reports participation on a data safety monitoring board or advisory board of PharmaMar, Roche, Merk, Lilly, Eisai, and Karyopharm; NC reports advisory and consultancy role for Roche, PharmaMar, AstraZeneca, MSD/Merk, Clovis Oncology, Tesaro, GSK, Novartis, Pfizer, Takeda, BIOCAD, Immunogen, Mersana, Eisai, and OncXerna MH reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK and Clov s Oncology; reports articipation on a data safety monitoring board or advisory board of Amgen, GSK, and Clovis Oncology; reports receipt of equipment, materials, drugs, medical writing, gifts, or other services from Clovis Oncology, BMS, and Merck educational grants for clinical trials. AJ is employee at Premier Research, the CRO conducting the study. IA-F, AZ, and HB are employees or consultants at Glycotope, the sponsor of the study. In addition, HB owns stock or stock option of Glycotope. JS reports grants or contracts from Roche, GSK, AstraZeneca, Clovis, MSD, Merck, and Eisai; and participation in advisory boards at Roche, GSK, AstraZeneca, Clovis, MSD, Merck, Eisai as well as a Congress Leadership President at NOGGO. All other authors have declared no conflicts of interest. (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ledermann Jonathan, A., et al. (2023). "Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100." Gynecologic Oncology 178: 119-129.
	Objective: This prespecified exploratory analysis evaluated the association of gene expression signatures, tumor mutational burden (TMB), and multiplex immunohistochemistry (mIHC) tumor microenvironment-associated cell phenotypes with clinical outcomes of pembrolizumab in advanced recurrent ovarian cancer (ROC) from the phase II KEYNOTE-100 study.; Methods: Pembrolizumab-treated patients with evaluable RNA-sequencing (n = 317), whole exome sequencing (n = 293), or select mIHC (n = 125) data were evaluated. The association between outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) and gene expression signatures (T-cell-inflamed gene expression profile [Tcell inf GEP] and 10 non-Tcell inf GEP signatures), TMB, and prespecified mIHC cell phenotype densities as continuous variables was evaluated using logistic (ORR) and Cox proportional hazards regression (PFS; OS). One-sided p-values were calculated at prespecified α = 0.05 for Tcell inf GEP, TMB, and mIHC cell phenotypes and at α = 0.10 for non-Tcell inf GEP signatures; all but Tcell inf GEP and TMB were adjusted for multiplicity.; Results: No evidence of associations between ORR and key axes of gene expression was observed. Negative associations were observed between outcomes and Tcell inf GEP-adjusted glycolysis (PFS, adjusted-p = 0.019; OS, adjusted-p = 0.085) and hypoxia (PFS, adjusted-p = 0.064) signatures. TMB as a continuous variable was not associated with outcomes (p > 0.05). Positive associations were observed between densities of myeloid cell phenotypes CD11c + and CD11c + /MHCII - /CD163 - /CD68 - in the tumor compartment and ORR (adjusted-p = 0.025 and 0.013, respectively).; Conclusions: This exploratory analysis in advanced ROC did not find evidence for associations between gene expression signatures and outcomes of pembrolizumab. mIHC analysis suggests CD11c + and CD11c + /MHCII - /CD163 - /CD68 - phenotypes representing myeloid cell populations may be associated with improved outcomes with pembrolizumab in advanced ROC.; Clinical Trial Registration: ClinicalTrials.gov, NCT02674061.; Competing Interests: Declaration of Competing Interest J.A. Ledermann reports receiving research grants from AstraZeneca and Merck/MSD; lecture fees from Clovis Oncology, AstraZeneca, Neopharm, GSK and MSD/Merck; and advisory board fees from AstraZeneca, GSK, Artios Pharma, Clovis Oncology, ImmunoGen, Mersana, Bristol Myers Squibb, Nuvation, Ellipses Pharma, VBL Therapeutics, Eisai, Regeneron, and Immagene, outside of the submitted work. R. Shapira-Frommer reports receiving support with medical writing for the submitted work from MSD; a research grant from MSD; consulting fees paid to her from MSD and Clovis Oncology; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events paid to her from MSD, Bristol Myers Squibb, Roche, AstraZeneca, Sanofi, Medison Pharma, Neopharm, and Novartis; participation on a data safety monitoring board or advisory board for MSD (received personal fee), Novartis (received personal fee), and AstraZeneca (unpaid); and a role in the ENGOT early phase study group (unpaid), outside of the submitted work. A.D. Santin reports grants or contracts paid to his institution from Genentech, Immunomedics, Gilead, Merck, Boehringer Ingelheim, and Tesaro; consulting fees paid to him from Merck, Eisai, and R-Pharm US; and participation on a data safety monitoring board or advisory board for Merck, Eisai, and R-PHARM US, outside of the submitted work. A.S. Lisyanskaya reports no disclosures. S. Pignata reports receiving payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from MSD, GSK, Roche, AstraZeneca, and Clovis Oncology, outside of the submitted work. I. Vergote reports contracted research via KU Leuven to his institution from Oncoinvent AS; corporate-sponsored research to his institution from Amgen and Roche; consulting fees paid to him from Agenus, Akesobio, AstraZeneca, Brist l Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, Roche, Genmab, GSK, ImmunoGen, Jazz Pharmaceuticals, Karyopharm Therapeutics, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, and Zentalis; and travel support to himself from Karyopharm Therapeutics, Genmab, and Novocure, outside of the submitted work. F. Raspagliesi reports receiving grants or contracts from GSK, MSD, and AstraZeneca; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from GSK, MSD, and AstraZeneca; and support for attending meetings and/or travel from GSK, outside of the submitted work. G.S. Sonke reports payments to his institution for inclusion of trial subjects and medical writing support, all from MSD, for the submitted work; institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche, and Seagen; and consulting fees paid to his institution from Biovica, Novartis, and Seagen, outside of the submitted work. M. Birrer reports no disclosures. D.M. Provencher reports receiving payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from AstraZeneca and GSK and participation on a data safety monitoring board or advisory board for GSK, outside of the submitted work. J. Sehouli reports receiving consulting fees from Roche, GSK, Tesaro, Novocure, Clovis Oncology, MSD, Merck, Pfizer, and Astra Zeneca; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Roche, GSK, Tesaro, Novocure, Clovis, MSD, Merck, Pfizer, Astra Zeneca, and Eisai; support for attending meetings and/or travel from Roche, GSK, Tesaro, and AstraZeneca; participation on a data safety monitoring board or advisory board for Roche, GSK, Tesaro, Novocure, Clovis Oncology, MSD, Merck, Pfizer, AstraZeneca, Eisai, and PharmaMar; and roles on/as the council of ESGO), president of NOGGO, president of PARSGO, speaker of the Ovarian Cancer Commission (AGO), and delegate to GCIG, outside of the submitted work. N. Colombo reports receiving medical writing support from MSD for the submitted work; grants or contracts paid to her from MSD, Roche, and GSK; consulting fees paid to her from MSD, Roche, GSK, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events to her from AstraZeneca, GSK, Novartis, Clovis Oncology, and MSD; support for attending meetings and/or travel from AstraZeneca, MSD, and GSK; participation on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD/Merck, Nuvation Bio, OncXerna Therapeutics, Pfizer, Pieris, and Roche; and unpaid roles for ACTO Onlus and ESMO Guidelines Committee, outside of the submitted work. A. González-Martín reports receiving grants or contracts from Roche, GSK, and CCUN; consulting fees paid to him from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, HederaDx, ImmunoGen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, Sutro Biopharma, Seagen, and Takeda; consulting fees paid to him from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, HederaDx, ImmunoGen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, Sutro Biopharma, Seagen, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events paid to him from GSK, Clovis, AstraZeneca, MSD, Mersana, and Roche; support for attending meetings and/or travel paid to him from AstraZeneca/MSD and GSK; and unpaid roles as president of GEICO and ENGOT, outside of the submitted work. A. Oaknin reports grants or contracts paid to her institution from AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Bristol Myers Squibb, Clovis Oncology Inc., Eisai, Roche, ImmunoGen, MSD de España S.A., Millennium Pharmaceuticals, PharmaMar SA, Regene on Pharmaceuticals, and Tesaro; consulting fees paid to her from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, Roche, Genmab, GSK, ImmunoGen, Itheos, MSD de España, S.A., Mersana Therapeutics, Novocure, PharmaMar, prIME Oncology, Roche, Sattucklabs, Seagen, Sutro Biopharma, and Tesaro; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ESMO, Edizioni Minerva Medica SpA, and Doctaforum Servicios S.L; support for attending meetings and/or travel paid to her from AstraZeneca, PharmaMar, and Roche; and payment to her for participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, Roche, Genmab, GSK, ImmunoGen, Itheos, MSD de España S.A., Mersana Therapeutics, Novocure, PharmaMar, prIME Oncology, Roche, Sattucklabs, Seagen, Sutro Biopharma, and Tesaro, outside of the submitted work. P. B. Ottevanger reports receiving support for manuscript writing and provision of study patients from MSD for the submitted work. V. Rudaitis reports no disclosures. J. Kobie is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and has stock in Merck & Co., Inc., Rahway, NJ, USA. M. Nebozhyn is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and has stock in Merck & Co., Inc., Rahway, NJ, USA, and reports a pending patent (WO 2020/167619) related to the application of angiogenesis and mMDSC gene expression-based biomarker of tumor response to PD-1 antagonists. M. Edmondson is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Y. Sun is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and has stock in Merck & Co., Inc., Rahway, NJ, USA. R. Cristescu is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and has stock in Merck & Co., Inc., Rahway, NJ, USA; and reports a pending patent (WO 2020/167619) related to the application of Angiogenesis and mMDSC gene expression-based biomarker of tumor response to PD-1 antagonists. P. Jelinic is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. S.M. Keefe is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and has stock in Merck & Co., Inc., Rahway, NJ, USA. U.A. Matulonis reports consulting fees paid to her from Merck, GSK, and AstraZeneca; payment made to her from Med Learning Group for her role on the committee on endometrial cancer, which involved creation of the entire lecture and slides; payment made to her for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Research to Practice; payments made to her for participation on the advisory board for Allarity, NextCure, Trillium, Agenus, ImmunoGen, Novartis, Boehringer Ingelheim, Rivkin Foundation, Ovarian Cancer Research Alliance, Clearity Foundation, MorphoSys, and CureLab; and payments for participation on a data safety monitoring board for Alkermes and Symphogen, outside of the submitted work. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lee, A. (2021). "Niraparib: a Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer." Targeted oncology 16(6): 839‐845.
	Niraparib (Zejula™) is a PARP inhibitor which is approved for maintenance therapy in adults with advanced ovarian cancer in complete or partial response to platinum‐based chemotherapy. In a placebo‐controlled phase III trial in patients with newly diagnosed advanced ovarian cancer, niraparib significantly extended progression free survival in two predefined populations, namely a patient population with altered homologous‐recombination DNA repair pathways [i.e. homologous‐recombination deficiency positive (HRd)] and the overall trial population. A prespecified exploratory subgroup analysis indicated that niraparib was also efficacious in patients who were homologous recombination deficiency negative or homologous recombination proficient (HRp). Niraparib has a manageable tolerability profile with myelosuppression as the main safety concern. Haematological reactions were managed with monitoring and dose reduction or interruption. A weight‐ and platelet count‐based individualised dosage regimen introduced during the trial (and subsequently approved) appeared to improve haematological tolerability. Niraparib is a useful option for first‐line maintenance therapy for advanced ovarian cancer in adults who responded to platinum‐based chemotherapy, regardless of homologous‐recombination deficiency status and is a promising option for HRp patients, for whom maintenance treatment options are limited.

Lee, A. (2022). "MYL-1402O: A Bevacizumab Biosimilar." Targeted oncology 17(1): 85-88.
	MYL-1402O (Abevmy ® , Lextemy ® ) is a biosimilar of the reference anti-vascular endothelial growth factor antibody bevacizumab. Abevmy ® is approved for use in all indications for which reference bevacizumab is approved, including the treatment of non-small cell lung cancer (NSCLC) and other solid cancers. Lextemy ® is approved for all indications as reference bevacizumab, except in recurrent ovarian cancer. MYL-1402O has similar physicochemical and pharmacodynamic properties to those of reference bevacizumab, and the pharmacokinetic similarity of the agents has been shown in healthy male subjects. MYL-1402O demonstrated clinical efficacy equivalent to that of reference bevacizumab in patients with non-squamous NSCLC. The tolerability, safety and immunogenicity profiles of MYL-1402O were consistent with those of reference bevacizumab. The role of reference bevacizumab in the management of solid cancers is well established and MYL-1402O provides an effective biosimilar alternative for patients requiring bevacizumab therapy. (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Lee, A. J., et al. (2023). "Fertility-sparing hormonal treatment in patients with stage I endometrial cancer of grade 2 without myometrial invasion and grade 1-2 with superficial myometrial invasion: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-2001)." Gynecologic Oncology 174: 106-113.
	Objectives: To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI.; Methods: Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST.; Results: Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST.; Conclusion: The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation. (Copyright © 2023. Published by Elsevier Inc.)

Lee, B., et al. (2024). "Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines." Journal of Gynecologic Oncology 35(1): e43.
	Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.Copyright © 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Lee Byung, M., et al. (2023). "Radiotherapy in recurrent ovarian cancer: updated results of involved-field radiation therapy." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(7): 1106-1111.
	Objective: This study aimed to update the possible clinical benefits of radiation therapy in recurrent ovarian cancer.; Methods: The medical records of 495 patients with recurrent ovarian cancer after initially undergoing maximal cytoreductive surgery and adjuvant platinum-based chemotherapy based on the pathologic stage between January 2010 and December 2020 were analyzed: 309 and 186 patients were treated without and with involved-field radiation therapy, respectively. Involved-field radiation therapy is defined as radiation therapy only to the areas of the body involved by tumor. The prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). Overall survival was compared between patients treated with and without involved-field radiation therapy. The favorable group was defined as patients who satisfied at least four of the following factors: good performance, no ascites, normal CA-125, platinum-sensitive tumor, and nodal recurrence.; Results: The median age of the patients was 56 years (range 49-63) and median time to recurrence was 11.1 months (range 6.1-15.5). 217 patients (43.8%) were treated at a single site. Radiation therapy, performance status, CA-125, platinum sensitivity, residual disease, and ascites were all significant prognostic factors. The 3-year overall survival of all patients, patients treated without radiation therapy, and patients treated with radiation therapy was 54.0%, 44.8%, and 69.3%, respectively. Radiation therapy was associated with higher overall survival rates in the unfavorable and favorable patient groups. Patient characteristics showed higher rates of normal CA-125, lymph node metastasis only, lower platinum sensitivity, and higher rates of ascites in the radiation therapy group. After propensity score matching, the radiation therapy group showed superior overall survival to the non-radiation therapy group. Normal CA-125, good performance status, and platinum sensitivity were associated with a good prognosis in patients treated with radiation therapy.; Conclusion: Our study showed that higher overall survival was observed in patients treated with radiation therapy in recurrent ovarian cancer.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Lee Chee, K., et al. (2021). "Molecular and clinical predictors of improvement in progression-free survival with maintenance PARP inhibitor therapy in women with platinum-sensitive, recurrent ovarian cancer: A meta-analysis." Cancer 127(14): 2432-2441.
	Background: The authors performed a meta-analysis to better quantify the benefit of maintenance poly(ADP-ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum-sensitive, recurrent, high-grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild-type BRCA but homologous recombinant-deficient (HRD), homologous recombinant-proficient (HRP), and baseline clinical prognostic characteristics.; Methods: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression-free survival were pooled across trials using the inverse variance weighted method.; Results: Four trials included 972 patients who received a PARPi (olaparib, 31%; niraparib, 35%; or rucaparib, 34%) and 530 patients who received placebo. For patients who had germline BRCA1 mutation (gBRCAm1) (N = 471), the hazard ratio (HR) was 0.29 (95% CI, 0.23-0.37); for those who had germline BRCA2 mutation (gBRCAm2) (N = 236), the HR was 0.26 (95% CI, 0.17-0.39); and, for those who had sBRCAm (N = 123), the HR was 0.22 (95% CI, 0.12-0.41). The treatment effect was similar between the gBRCAm and sBRCAm subsets (P = .48). In patients who had wild-type BRCA HRD tumors (excluding sBRCAm; N = 309), the HR was 0.41 (95% CI, 0.31-0.56); and, in those who had wild-type BRCA HRP tumors (N = 346), the HR was 0.64 (95% CI, 0.49-0.83). The relative treatment effect was greater for the BRCAm versus HRD (P = .03), BRCAm versus HRP (P < .00001), and HRD versus HRP (P < .00001) subsets. There was no difference in benefit based on age, response after recent chemotherapy, and prior bevacizumab.; Conclusions: In platinum-sensitive, recurrent, high-grade ovarian cancer, maintenance PARPi improves progression-free survival for all patient subsets. PARPi therapy has a similar magnitude of benefit for sBRCAm and gBRCAm. Although patients with BRCAm derive the greatest benefit, the absence of a BRCAm or HRD could not be used to exclude patients from maintenance PARPi therapy. (© 2021 American Cancer Society.)

Lee, H., et al. (2021). "Interventional benefit of Pilates using Oov and mat on middle-aged women with lower urinary tract symptoms: emphasis on abdominal muscle thickness and muscular function." Journal of exercise rehabilitation 17(3): 192-197.
	Lower urinary tract symptoms (LUTS) have been considered as clinically prevalent symptom in women, and can be ameliorated by the change of abdominal muscles and pelvic floor muscle (PFM). This study investigated the efficacy of Pilates program using Oov and mat on the change of abdominal muscle thickness, PFM function, and LUTS clinical score. 53 women experiencing LUTS were randomly assigned to Oov Pilates exercise group (OPEG) (n=20), mat Pilates exercise group (MPEG) (n= 16), and symptomatic control group (SCG) (n=17), respectively, and two groups using Oov and mat participated in 8-week Pilates program. Thickness of abdominal muscle, functional movement of PFM, and LUTS clinical score were measured from all groups. Thickness of rectus abdominis, internal oblique abdominis, transversus abdominis was significantly improved in OPEG (P<0.05), however, MPEG showed a significant change only in transversus abdominis (P<0.05). In all abdominal muscles, OPEG had a significantly improved abdominal muscle thickness compared to SCG (P<0.05). Functional movement of PFM in OPEG was significantly decreased (P<0.005), but not in MPEG and SCG. In LUTS clinical score, OPEG and MPEG showed a significantly abated symptoms in degree of voiding-related symptoms and discomfort (P<0.005), but not in SCG. Our study highlighted that Pilates using Oov can be an effective intervention to ameliorate the quantitative quality of abdominal muscle thickness and PFM, which ultimately provides the satisfied self-clinical index in degree of voiding-related symptoms and discomfort.

Lee Hye, W., et al. (2021). "Aromatherapy for Managing Menopausal Symptoms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials." Journal of alternative and complementary medicine (New York, N.Y.) 27(10): 813-823.
	Background: Aromatherapy is widely used in women's health as a complementary therapy. Objective: This review aimed to critically evaluate clinical evidence of the effectiveness of aromatherapy in managing menopausal symptoms. Design: A systematic review and meta-analysis. Methods: A total of 11 electronic databases were searched up to November 5, 2020. Randomized controlled trials (RCTs) evaluating any type of aromatherapy against placebo in menopausal individuals were eligible. Two authors independently assessed the study eligibility and risk of bias as well as extracted the data for each study. Cochrane risk of bias tool was used to evaluate the methodological quality of each included studies. No ethical approval was required for this manuscript as this study did not involve human subjects or laboratory animals. Results: Seven RCTs met our inclusion criteria and were analyzed. Most of the included RCTs had low risk of bias in most domains except for blinding. Four studies tested the efficacy of aromatherapy for menopausal symptoms. The results showed that aromatherapy (lavender or low dose of neroli) inhalation had superior effects on reducing the total menopausal symptom score compared with the placebo. One study presented that aromatherapy massage with mixed oils reduced menopausal symptoms. Three studies investigated the effects of aromatherapy inhalation on sexual desire, and all of the studies showed that aromatherapy inhalation (lavender or low dose of neroli or mixed oils) had superior effects compared with the placebo. Conclusion: This review indicates limited evidence of the benefit of aromatherapy (lavender or low dose of neroli) in improving total menopausal symptoms and sexual desire. Further studies are highly warranted to validate the findings.

Lee Hye, W., et al. (2021). "Fennel (Foeniculum vulgare Miller) for the management of menopausal women's health: A systematic review and meta-analysis." Complementary Therapies in Clinical Practice 43: 101360.
	This review aimed to evaluate the current evidence on the effectiveness and safety of fennel (Foeniculum vulgare Miller) for managing menopausal women's health. Fourteen databases were searched. We included randomized controlled trials (RCTs) that evaluated any type of fennel treatment in menopausal women. Seven RCTs that met our inclusion criteria were identified and analyzed. The included RCTs had concerning risks of bias in general. Two RCTs compared the effects of fennel with placebo, and the meta-analysis results favored fennel for improving menopausal symptoms (n = 145, standard mean difference -1.32 [-1.76, -0.87], p < 0.00001). Other studies failed to show beneficial effects of fennel in terms of sexual function, quality of life (QoL), and psychological health. No serious adverse events were reported. Our review presented evidence for fennel improving menopausal symptoms. However, the effectiveness and safety of fennel in improving QoL, and psychological health remains unclear. (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lee Hye, W., et al. (2022). "Using ginseng for menopausal women's health care: A systematic review of randomized placebo-controlled trials." Complementary Therapies in Clinical Practice 48: 101615.
	Purpose: This systematic review aimed to update the evidence of ginseng on menopausal women's health care.; Methods: We searched six databases (PubMed, AMED, EMBASE, the Cochrane Library, RISS, and KoreaMed) from their inception to April 2022 and included all placebo-controlled RCTs comparing any type of ginseng in menopausal women. The methodological quality of all studies was assessed using the Cochrane Risk of Bias Tool 2.0.; Results: We included 15 RCTs with our inclusion criteria. The majority of studies considered bias a concern. Ginseng reduced menopausal symptoms in three studies (n = 515; standardized mean difference (SMD): -0.40, 95% confidence interval (CI): -0.73 to -0.07, P = 0.02) and lowed hot flashes (n = 515; SMD: -0.34, 95% CI: -0.66 to -0.01, P = 0.04). The meta-analysis of three other studies failed to show that ginseng was beneficial for sexual function (n = 491; SMD: 0.31, 95% CI: -0.30 to 0.92, P = 0.32). Three RCTs showed positive effects of ginseng on the quality of life score (n = 515, SMD: -0.31, 95% CI: -0.61 to -0.01, P = 0.05). In two studies, ginseng failed to produce significant effects on the vaginal maturation index and vaginal pH. Another three RCTs failed to demonstrate a beneficial effect of Korean red ginseng (KRG) on endometrial thickness.; Conclusion: This study demonstrated that ginseng can significantly reduce hot flashes, menopausal symptoms, and quality of life in menopausal women. In contrast, neither KRG nor ginseng appeared to have any direct effect on sexual dysfunction, hormones or biomarkers, or endometrial thickness. More rigorous RCTs are needed to overcome the current limitations. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lee Hye, W., et al. (2020). "Fennel for Reducing Pain in Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Nutrients 12(11).
	Fennel is used as an alternative treatment for primary dysmenorrhea. This review aims to evaluate the effectiveness and safety of fennel for reducing pain in primary dysmenorrhea. Twenty databases, including English, Korean, Chinese, Japanese, Iranian, and Spanish databases, were searched from inception to 20 October 2020. All randomized controlled trials (RCTs) investigating the effectiveness of fennel for treating primary dysmenorrhea were considered. Two reviewers conducted the data extraction and risk of bias assessment independently. Any discrepancies were resolved through discussion with a third reviewer. A total of 12 studies were included in this review. The pooled results of seven trials showed that the effect of fennel is similar to that of conventional drug therapies in alleviating pain ( n = 502, standardized mean difference (SMD): 0.07, 95% confidence interval(CI): -0.08 to 0.21, p < 0.37, I 2 = 0%). In comparison with placebo, fennel was seen to have favorable effects on reducing pain in primary dysmenorrhea ( n = 468, SMD: -3.27, 95% CI: -5.28 to -1.26, p = 0.001, I 2 = 98%). Only three studies assessed adverse events (AEs), and one study reported minor AEs. Although the risk of bias for all the included studies was moderate, potential publication bias was observed due to the presence of a greater number of small studies with favorable effects. This systematic review concludes that fennel is as effective as conventional drug therapies in alleviating pain in primary dysmenorrhea. More studies that include more diverse populations and robust evidence of fennel's effects will be needed in future research endeavors.

Lee Hyo, C., et al. (2023). "High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial." Gynecologic Oncology 177: 142-149.
	Objective: Radiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer.; Methods: This was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival.; Results: Progression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%).; Conclusion: High-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS.; Clinical Trial Information: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.; Competing Interests: Declaration of Competing Interest The authors declare no financial or other interest that is relevant to this article. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lee Hyune, J., et al. (2021). "Repetitive transcranial magnetic stimulation treatment for peripartum depression: systematic review & meta-analysis." BMC Pregnancy and Childbirth 21(1): 118.
	Background: Peripartum depression is a common disorder with very high potential hazards for both the patients and their babies. The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression.; Methods: We performed a systematic review that followed the PRISMA guidelines. We searched for studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference, and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method.; Results: The therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.944-1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.689-1.459), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346 (95% CI: 0.214-0.506), a meaningful result. There were no severe side effects to the mothers or fetuses.; Conclusions: From various perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results.

Lee, I. S., et al. (2019). "Central and Peripheral Mechanism of Acupuncture Analgesia on Visceral Pain: A Systematic Review." Evidence-based Complementary and Alternative Medicine 2019: 1304152.
	Background/Aims. Despite the wide use of acupuncture for the management of visceral pain and the growing interest in the pathophysiology of visceral pain, there is no conclusive elucidation of the mechanisms behind the effects of acupuncture on visceral pain. This systematic review aims to provide an integrative understanding of the treatment mechanism of acupuncture for visceral pain. Methods. Electronic and hand searches were conducted to identify studies that involved visceral pain and acupuncture. Results. We retrieved 192 articles, out of which 46 studies were included in our review. The results of our review demonstrated that visceral pain behaviors were significantly alleviated in response to acupuncture treatment in groups treated with this intervention compared to in sham acupuncture or no-treatment groups. Changes in the concentrations of beta-endorphin, epinephrine, cortisol, and prostaglandin E2 in plasma, the levels of c-Fos, substance P, corticotropin-releasing hormone, P2X3, acetylcholinesterase (AchE), N-methyl-D-aspartate (NMDA) receptors, and serotonin in the gut/spinal cord, and the neuronal activity of the thalamus were associated with acupuncture treatment in visceral pain. Conclusions. Acupuncture reduced visceral pain behavior and induced significant changes in neuronal activity as well as in the levels of pain/inflammation-related cytokines and neurotransmitters in the brain-gut axis. Further researches on the thalamus and on a standard animal model are warranted to improve our knowledge on the mechanism of acupuncture that facilitates visceral pain modulation.Copyright © 2019 In-Seon Lee et al.

Lee, J. (2019). "Physical activity, sitting time, and the risk of ovarian cancer: A brief research report employing a meta-analysis of existing." Health Care for Women International 40(4): 1-26.
	We investigated the associations between physical activity, physical inactivity, and ovarian cancer risk and identified the most effective physical activity intensity and amount to reduce ovarian cancer risk. Thirty-four studies were selected for the present meta-analysis. Physical activity helps decrease ovarian cancer risk. Moderate intensity and low amount of physical activity showed the greatest reduction of ovarian cancer risk and prolonged sitting time had the worst ovarian cancer risk. At least 2 h of moderate physical activity per week and <3 h of sitting time per day provided a preventive effect to ovarian cancer.

Lee, J. and G. Hong Dae (2022). "Comparison of Survival Outcomes Based on Pre-treatment Pleural Effusion in Advanced Epithelial Ovarian Cancer." Anticancer Research 42(10): 4937-4943.
	Background/aim: The influence of pleural effusion (PE) on survival outcomes in ovarian cancer has not been thoroughly evaluated. This study aimed to analyze the effect of pre-treatment PE on prognosis.; Patients and Methods: A total of 117 patients with stage III and IV epithelial ovarian cancer having pre-treatment PE were included in the study. Malignant PE was determined with CT or PET/CT or biopsy.; Results: Thirty patients (27.0%) had PE and 81 (73.0%) had no PE (NPE). For first-line chemotherapy, the delivered dose intensity was significantly higher in PE. In both groups, 5-year overall survival (OS) and progression-free survival (PFS) did not present statistical significant differences. The 7-year PFS of PE was significantly shorter unlike the OS.; Conclusion: Within 5 years, pre-treatment PE did not have a significant impact on OS nor PFS for patients with a higher dose of first-line chemotherapy. Within 7 years, better management strategies are needed as PE can have a negative impact on PFS. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Lee, J. and G. Hong Dae (2023). "Comparative study of supracervical hysterectomy between da Vinci SP ® surgical system and conventional single-site laparoscopy for uterine fibroid: single center experiences." Journal of Robotic Surgery 17(4): 1421-1427.
	This study aimed to review the surgical outcomes of supracervical hysterectomy using the da Vinci SP ® surgical system and conventional single-site laparoscopic surgery for uterine fibroids. This study included 79 patients who underwent supracervical hysterectomy with the da Vinci SP ® surgical system and conventional single-site laparoscopy for uterine fibroid between June 2018 and April 2021. All the surgeries were performed by an experienced surgeon. Surgical outcomes and complications were reviewed in both groups. No significant difference was found between the two groups with regards to the patients' preoperative surgical conditions such as weight of the uterus, history of pelvic surgery, and pelvic adhesion. A significantly longer operation time (p < 0.01) and higher levels of C-reactive protein (p < 0.01) were found in the robotic surgery group; in particular, the uterus-out time was significantly longer (p < 0.01). No significant differences were found in other surgical outcomes such as complication rates and hospital stays. Supracervical hysterectomy using the da Vinci ® SP surgical system is comparable to conventional single-site laparoscopy in uncomplicated cases. However, it requires a significantly longer operative time and has a higher inflammatory response. (© 2023. The Author(s).)

Lee, J. B., et al. (2021). "Phase 2 study of TAS-117, an allosteric akt inhibitor in advanced solid tumors harboring phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene mutations." Investigational New Drugs 39(5): 1366-1374.
	TAS-117 is a potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor. We conducted a single-arm single-center phase 2 study of TAS-117 in heavily treated patients with tumors refractory to systemic chemotherapy and harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations. Patients with gastrointestinal (GI) cancers were orally administered 16 mg TAS-117 daily, and those with non-GI tumors were administered 24 mg on a 4 days on/3 days off schedule. The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, safety, and tolerability. Thirteen patients were enrolled: eight with non-GI (breast, ovarian, endometrial, and non-small cell lung) and five with GI (colon, rectal, gastric, and gallbladder) cancers. Ten patients were treated with TAS-117 after ≥ 4 lines of therapy. Twelve patients showed PIK3 catalytic subunit alpha (PIK3CA) mutations; one harbored an Akt1E17K mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8 %, and DCR was 23 %. The median PFS and OS were 1.4 and 4.8 months, respectively. Grade 3-4 treatment-related adverse events were anorexia (grade 3, 8 %) and hyperglycemia (grade 3, 8 %; grade 4, 8 %).Grade 3-4 treatment-related adverse events occurred in 27 % of grade 3 anorexia (9 %) and hyperglycemia (grade 3, 8 %; grade 4, 9\%). TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in patients with breast cancer harboring PIK3CA H1047R and Akt1E17K mutations.Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017).

Lee, J.-M., et al. (2022). "Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial." Clinical cancer research : an official journal of the American Association for Cancer Research 28(19): 4186-4193.
	Purpose: The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer.; Patients and Methods: PARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined.; Results: Sixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group.; Conclusions: Clinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies. (©2022 The Authors; Published by the American Association for Cancer Research.)

Lee, J. Y., et al. (2021). "Efficacy and safety of transvaginal high-intensity focused ultrasound therapy in women with symptomatic uterine leiomyomas: A clinical trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 256: 302-307.
	OBJECTIVE: To evaluate the efficacy and safety of transvaginal high-intensity focused ultrasound (vHIFU) therapy in women with symptomatic uterine leiomyomas. METHODS: This first-in-human, two-center, prospective, unblinded, single-arm trial was performed in the Republic of Korea from December 2017 to February 2019. Premenopausal women with symptomatic, contrast-enhanced uterine leiomyomas with a diameter ≤5 cm were eligible. Under sedation or monitored anesthesia, leiomyomas were ablated with vHIFU under ultrasound guidance. The primary endpoint was the non-perfused volume (NPV) ratio measured immediately after therapy. Secondary endpoints were changes in Uterine Fibroid Symptom-Quality of Life (UFS-QOL) scores, dysmenorrhea visual analog scale (VAS), uterine leiomyoma volume, rate of subsequent therapy, and treatment-emergent adverse events (TEAE). RESULTS: Thirty-five women were screened; 13 women were enrolled and underwent vHIFU therapy for 33 uterine leiomyomas. NPV ratios were 0.76 ± 0.27 (mean ± SD); the lower limit of a one-sided 97.5 % confidence interval was 0.67, surpassing the non-inferiority cut-off of 0.50. UFS-QOL scores (symptom severity score, median, baseline: 66.60, 3-month follow-up: 32.85; p = 0.0010; health related quality of life score, median, baseline: 41.40, 3-month follow-up: 73.30; p = 0.0010) and dysmenorrhea VAS (mean, baseline: 50.92, 3-month follow-up: 20.67; p = 0.0019) improved significantly. Volume of uterine leiomyoma was reduced (median, baseline: 8.10 cm3, 3-month follow=-up: 5.30 cm3; p < 0.0001), and none received subsequent therapy. Twenty-six TEAEs from 8 participants were observed, and all TEAEs were resolved without sequelae. CONCLUSION: vHIFU therapy exhibited promising efficacy and safety and might be considered as a treatment option for women with symptomatic uterine leiomyomas. Registration: This trial was registered at: www.clinicaltrial.gov (NCT03328260).

Lee, J.-Y., et al. (2022). "Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial." Journal of Gynecologic Oncology 33(4): e45.
	Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options.; Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m² D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1).; Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2-10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed.; Conclusion: This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.; Trial Registration: ClinicalTrials.gov Identifier: NCT03699449.; Competing Interests: JYL reports grants from AstraZeneca during the conduct of the study; grants and personal fees from Beigene, Bergenbio, Clovis Oncology, Immunogen, Janssen, Merck, MSD, Novartis, Roche, Seagen, Synthon, and Takeda. All other authors have no conflicts of interest to disclose. (Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Lee, J.-Y., et al. (2023). "Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy." JAMA Surgery 158(11): 1133-1140.
	Importance: Hyperthermic intraperitoneal chemotherapy (HIPEC) followed by interval cytoreductive surgery (ICS) has shown survival benefits for patients with advanced-stage ovarian cancer. However, there is still a lack of consensus regarding the integration of HIPEC into clinical practice.; Objective: To evaluate the safety and effectiveness of ICS with HIPEC compared with ICS alone in clinical practice for patients with advanced-stage ovarian cancer.; Design, Setting, and Participants: This prospective, multicenter, comparative effectiveness cohort study enrolled 205 patients with stage III or IV ovarian cancer who had received at least 3 cycles of neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC at 7 Korean Gynecologic Oncology Group institutions between September 1, 2017, and April 22, 2022. Nine patients were excluded because they did not meet the inclusion criteria.; Exposures: Neoadjuvant chemotherapy followed by ICS with HIPEC or ICS without HIPEC.; Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Overall survival (OS) and the safety profile were the key secondary end points.; Results: This study included 196 patients (median age, 58.0 years [range, 38-82 years]), of whom 109 underwent ICS with HIPEC and 87 underwent ICS without HIPEC. The median duration of follow-up was 28.2 months (range, 3.5-58.6 months). Disease recurrence occurred in 128 patients (65.3%), and 30 patients (15.3%) died. Interval cytoreductive surgery with HIPEC was associated with a significant improvement in median PFS compared with ICS without HIPEC (22.9 months [95% CI, 3.5-58.6 months] vs 14.2 months [95% CI, 4.0-56.2 months]; P = .005) and median OS (not reached [95% CI, 3.5 months to not reached] vs 53.0 [95% CI, 4.6-56.2 months]; P = .002). The frequency of grade 3 or 4 postoperative complications was similar in both groups (ICS with HIPEC, 3 of 109 [2.8%] vs ICS without HIPEC, 3 of 87 [3.4%]; P > .99). Among patients with recurrence, the frequency of peritoneal recurrence was lower in the ICS with HIPEC group than in the ICS without HIPEC group (21 of 64 [32.8%] vs 41 of 64 [64.1%]; P = .001).; Conclusions and Relevance: This study suggests that ICS in conjunction with HIPEC was associated with longer PFS and OS than ICS without HIPEC for patients with advanced-stage ovarian cancer and was not associated with higher rates of postoperative complications. The lower rate of peritoneal recurrence after HIPEC may be associated with improved OS.

Lee, K. and A. Wang (2020). "Trends in Oncology: an Updated Review of Minimally Invasive Surgery vs. Traditional Open Surgery." Journal of Interdisciplinary Medicine 5(4): 129-136.
	Objective: To review the recent trends in methodology for the most frequent oncological surgeries. More specifically, this paper will compare the minimally invasive methods to the conventional open method. It aims to find out whether minimally invasive surgeries are feasible treatments for certain types of cancers. Method(s): A review of retrospective studies searched in PubMed, Cochrane Library etc. was used to identify the studies published on this topic within a period of 6 years. Oncologic outcomes, postoperative complications/outcomes, and intraoperative outcomes were the main variables in the comparison to the surgical methods under review. Conclusion(s): Despite the recent controversy with minimally invasive surgery being contraindicated for cervical cancer, it is still an acceptable method for other types of common cancers. However, there are limitations to the approach, and the surgeon should make a prudent selection between minimally invasive and open surgery depending on the type of tumor and patient characteristics. Further studies, especially with randomized control trials, must be conducted.Copyright © 2020 Kyuwon Lee et al., published by Sciendo 2020.

Lee Kwang, B., et al. (2023). "Using Type I Collagen Gel to Prevent Postoperative Intrauterine Adhesion: A Multicenter Retrospective Study." Journal of Clinical Medicine 12(11).
	We evaluated the clinical outcomes of using type 1 collagen gel after therapeutic resectoscopy; overall, 150 women aged > 20 who planned to undergo therapeutic resectoscopy were enrolled. The patients were randomly assigned to either of the anti-adhesive treatment groups: the type 1 collagen gel (Collabarrier ® ) (study group; N = 75) or the sodium hyaluronate and sodium carboxymethylcellulose gel group (control group; N = 75) after resectoscopy. One month after applying anti-adhesive materials, postoperative intrauterine adhesions were evaluated using second-look hysteroscopy; the incidence rate of postoperative intrauterine adhesions examined through second-look hysteroscopy showed no significant differences between the groups. There were no statistical differences between the frequency and mean scores of the type and intensity of adhesions in both groups. Finally, no significant differences in adverse events, serious adverse events, adverse device effects, and serious adverse device effects were noted between the two groups; type 1 collagen gel can be effectively and safely used in intrauterine surgery to minimize postoperative adhesions, thereby eventually decreasing the prevalence of infertility, secondary amenorrhea, and recurrent pregnancy loss in reproductive women.

Lee, L. and U. Matulonis (2019). "Immunotherapy and radiation combinatorial trials in gynecologic cancer: A potential synergy?" Gynecologic Oncology 154(1): 236-245.
	Immunotherapy (IO) is an important new pillar in the treatment of solid tumors, and the integration of IO agents with chemotherapy, targeted therapy, surgery and radiation has yet to be defined. As preclinical and clinical studies have described synergistic activity with the combination of radiation and immunotherapy, many clinical trials are underway to explore both the safety and efficacy of this approach both in the metastatic and definitive setting. Through immune priming, radiation may enhance local tumor control at the irradiated site, as well as induce a systemic response to control distant metastasis, known as the abscopal effect. On a mechanistic level, radiation therapy releases tumor neoantigens and activates an adaptive immune response that is mediated by cytotoxic T-cells, which then hone to sites of irradiated tumor as well as non-irradiated tumor metastases to induce immunogenic tumor cell death. Although the abscopal effect is rare in clinical practice, strategies that combine immune checkpoint blockade with radiation are being studied to overcome immune tolerance or suppression and increase systemic response rates to IO agents. Gynecologic cancers are attractive targets for immune checkpoint blockade, and IO agents may be used in combination with definitive chemoradiotherapy to enhance radiosensitivity and thus local control for unresected disease as well as control distant micrometastatic spread. For patients with metastatic disease, immune checkpoint blockade in combination with stereotactic radiotherapy is being evaluated as a strategy for immune activation and tumor cytoreduction. In this review, we highlight the current use of IO agents in gynecologic cancer, describe the immunogenic potential of radiation through clinical observation and preclinical study, and discuss strategies for combining IO and radiation in reported and ongoing clinical trials.

Lee, M., et al. (2023). "Efficacy of the PRO-CTCAE mobile application for improving patient participation in symptom management during cancer treatment: a randomized controlled trial." Supportive Care in Cancer 31(6): 321.
	Purpose: Although mobile-based symptom monitoring is expected to improve patient participation in symptom management during anticancer therapy, previous trials have not evaluated its effectiveness. Therefore, this study aims to evaluate the impact of a symptom monitoring mobile application on improving patient participation in symptom management during anticancer therapy. Method(s): We conducted a single-center, open-label, randomized controlled trial that enrolled patients with breast, lung, head and neck, esophageal, or gynecologic cancer who were scheduled to receive anticancer therapy (oral or intravenous) between October 2020 and March 2021. We excluded patients with physical or psychological problems. The intervention group received a symptom monitoring application for 8 weeks, and the control group received the usual clinical practice. At 8 weeks, the improvement in patient participation in symptom management was assessed, and additionally quality of life and unplanned clinical visits were assessed. Result(s): A total of 222 patients were included in the analysis, of whom 142 were randomly assigned to the intervention group and 71 to the control group. The intervention group reported better outcome in patient participation in symptom management than the control group at 8 weeks (mean scores of 8.5 vs. 8.0; P = 0.01). There were no significant differences between the groups in Quality of life (P = 0.88) and unplanned clinical visits (P = 0.39-0.76). Conclusion(s): This study is meaningful in figuring out that the mobile-based symptom monitoring made them more engaged in their management. Future research should continue to evaluate the effects of patient participation as mediators of clinical outcomes. Trial registration: ClinicalTrials.gov NCT04568278.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Lee, S., et al. (2023). "Cost-effectiveness of POLE testing for high intermediate risk endometrial cancer (2242)." Gynecologic Oncology 176(Supplement 1): S280-S281.
	Objectives: The Cancer Genome Atlas identified four subtypes of endometrial cancer, and patients with DNA polymerase epsilon (POLE) ultramutated tumors have an improved prognosis. The high intermediate-risk subtype of endometrial cancer is a heterogenous group, and the patients with POLE in this group may benefit from surveillance instead of vaginal brachytherapy. This study sought to determine the cost-effectiveness of POLE testing in patients with stage I high intermediate-risk endometrial cancer. Method(s): A decision model was developed to compare POLE testing with next-generation sequencing and no POLE testing (TreeAge 2021, Williamstown, MA). A healthcare payor's perspective and a five-year time horizon were used. POLE-tested patients were assumed to undergo surveillance if positive, and if negative, received adjuvant vaginal brachytherapy. All patients without POLE testing underwent adjuvant treatment with vaginal brachytherapy. POLE testing was performed using next-generation sequencing (NGS). POLE prevalence was assumed to be 6% of those undergoing testing. Cost and utility data were derived from public databases and literature. The two strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness measured in quality-adjusted life years (QALYs), with a willingness to pay (WTP) threshold of $100,000 per QALY. One-way sensitivity analyses were performed by varying the prevalence of POLE mutations and the cost of testing. Result(s): Compared to universal treatment with vaginal brachytherapy, POLE testing with NGS had an incremental cost of $4681 with incremental effectiveness of 0.01 QALY, resulting in an ICER of $476,162. The sensitivity analyses showed that the model was most sensitive to variations in POLE prevalence. One-way sensitivity analysis suggested that the ICER crossed our WTP threshold at a POLE mutation prevalence of 15% and would be cost-effective. A second sensitivity analysis estimated that POLE testing was cost-effective at a WTP of $100,000 if the cost of POLE testing was less than $1639. Performing POLE testing with Sanger sequencing with a cost of $500 as opposed to NGS was associated with lower cost and increased QALYs compared to usual care with brachytherapy. Conclusion(s): POLE testing alone by NGS was not a cost-effective strategy in the high intermediate-risk endometrial cancer population. With its decreased costs, Sanger sequencing was cost-effective and below the WTP threshold. Continued research into high-fidelity yet less expensive methods to identify POLE tumors is warranted. [Formula presented]Copyright © 2023

Lee Seung, H., et al. (2020). "Efficacy of nerve-sparing radical hysterectomy vs. conventional radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis." Molecular and clinical oncology 12(2): 160-168.
	The aim of the present study was to compare the oncological outcome of nerve-sparing radical hysterectomy (NSRH) and conventional radical hysterectomy (CRH) for early-stage cervical cancer using a meta-analysis. A systematic review and meta-analysis was conducted, including 4 randomized controlled trials (RCT), 8 case-control and 11 comparative cohort studies comparing the morbidity, pelvic dysfunctions and oncological outcome between the two surgical methods. A total of 23 studies were included in this meta-analysis. The studies reported data of patients affected by cervical cancer; were written in English; included ≥20 patients; and reported data of patients with a comparison of clinical outcomes between NSRH and CRH. Data were extracted and risk of bias was assessed by four independent reviewers. A total of 1,796 patients were included: 884 patients (49.2%) undergoing NSRH and 912 (50.8%) undergoing CRH. The meta-analyses were conducted using Review Manager version 5.3 software, which is designed for conducting Cochrane reviews. As regards perioperative parameters, NSRH was found to be associated with a lower intraoperative blood loss and a shorter length of hospital stay in comparison with CRH. Patients undergoing NSRH experienced lower incidence of urinary, colorectal and sexual dysfunction compared with patients undergoing CRH. However, the resected parametrial width was favorable in patients with CRH, suggesting that NSRH was inferior to CRH in terms of radicality. The 5-year disease-free and overall survival rates were similar between the two groups. In this systematic review and meta-analysis, the collected data to date demonstrated that the nerve-sparing approach guarantees minimized surgical-related pelvic dysfunction, with similar oncological outcomes as CRH. However, further RCTs should be conducted to confirm the superiority and safety of NSRH. (Copyright: © Lee et al.)

Lee, S. H., et al. (2022). "Paracervical block in laparoscopic hysterectomy for postoperative pain control: a randomized, multi-center, double-blind, placebo-controlled trial." Clinical and Experimental Obstetrics and Gynecology 49(3): 066.
	Background: To determine the effect of a paracervical block in laparoscopic hysterectomy on postoperative pain relief. Method(s): A total of 86 patients scheduled for total laparoscopic hysterectomy for benign gynecologic diseases were randomly assigned to the experimental group (n = 43) and the control group (n = 43). Patients were received a paracervical injection that was either 10 mL of 0.5% bupivacaine with 1: 200,000 epinephrine or 10 mL of normal saline. The primary outcome was the postoperative pain score which was assessed using a visual analog scale at 2, 4, 6, 8, and 12 hours after surgery. The secondary outcome was the postoperative rescue analgesic requirement within 12 hours after surgery. Result(s): Baseline characteristics were similar in both groups. Postoperative pain scores did not significantly differ between groups. Rescue analgesia requirements were also statistically similar in both groups. Conclusion(s): Adding a paracervical block with preemptive local analgesia in patients undergoing laparoscopic hysterectomy did not reduce postoperative pain and postoperative rescue analgesia requirements.Copyright: © 2022 The Author(s).

Lee, S.-R. and D. Directo (2023). "Fish Oil Supplementation with Resistance Exercise Training Enhances Physical Function and Cardiometabolic Health in Postmenopausal Women." Nutrients 15(21).
	Menopause is a condition associated with an increased risk of dysregulation in cardiovascular and metabolic health among older women. While fish oil (FO) has garnered great attention for its health-enhancing properties, its potential for enhancing cardiometabolic health in this demographic remains to be established. The purpose of this study was to determine the clinical efficacy of an 8 wk administration of FO combined with programmed resistance exercise training (RET) on physical function and risk factors associated with cardiometabolic health in healthy older women. Twenty, healthy, older women were randomly assigned to one of the two experimental groups: resistance training with placebo (RET-PL) or RET with fish oil (RET-FO). Physical function, blood pressure (BP), triglyceride (TG), and systemic inflammation and oxidative stress biomarkers were assessed before and after the intervention. Statistical significance was set at p ≤ 0.05. Physical function was greatly enhanced in both RET and RET-FO. Handgrip strength substantially increased only in RET-FO. RET-FO exhibited significant decreases in BP, TG, inflammatory cytokines (TNF-α and IL-6), and oxidative stress (MDA and 8-OHdG) levels, while no detectable changes were found in RET-PL. Our findings indicate that FO administration during 8 wks of RET appears to enhance muscle function and lower risk factors linked to cardiometabolic disorders in postmenopausal women.

Lee, S. W., et al. (2022). "The Effects of Suburethral Tension Adjustable Sling (Remeex system) for Female Urinary Incontinence between Pure Intrinsic Sphincter Deficiency and Intrinsic Sphincter Deficiency with Overactive Bladder: Initial Experience with Propensity Score Matching." Clinical and Experimental Obstetrics and Gynecology 49(9): 193.
	Objective: To compare the therapeutic efficacy after suburethral adjustable sling (Remeex system) for female stress urinary incontinence (SUI) between pure intrinsic s phincter deficiency (ISD) and ISD with overactive bladder (OAB) group. Method(s): The study subjects were 86 female patients with ISD who underwent Remeex system to treat female SUI and who were available for 12 months follow-up. We retrospectively studied both patients who underwent Remeex system due to pure ISD (group I) and those who underwent Remeex system due to ISD with OAB (group II). Improvement in objective and subjective symptoms were retrospectively evaluated using a 1hr pad weight test, global response assessment (GRA) and overactive bladder symptom score (OABSS). Result(s): Group I included 43 patients and group II included 43 patients of mean ages 56.8 +/- 7.5 and 57.4 +/- 6.6 years, respectively. Use of 1 hr pad weight test showed that incontinence decreased after the procedures in both groups, and that of group I patients was significantly lower than that of group II patients. The mean GRA score was significant a higher score in group I. The OABSS of patients in group II were 8.2 +/- 1.1 and 7.2 +/- 1.1, respectively, before and at 12 months after operation, did differ significantly. The mean change of OABSS of group II patients was significantly more decreased than that of group I patients. Conclusion(s): The Remeex system showed a greater patient satisfaction and a higher cure rate in pure ISD than ISD with OAB in female patients with urinary incontinence.Copyright: © 2022 The Author(s).

Lee Yeh, C., et al. (2022). "Symptom burden and quality of life with chemotherapy for recurrent ovarian cancer: the Gynecologic Cancer InterGroup-Symptom Benefit Study." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(6): 761-768.
	Objective: The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with ≥3 lines of chemotherapy (PPS-ROC ≥3).; Methods: Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated ≥4 of 10 in at least one-third of symptoms in the MOST index. Improvement in MOST was defined as two consecutive scores of ≤3 in at least half of the symptomatic items at baseline. Improvement in HRQL was defined as two consecutive scores ≥10 points above baseline in the QLQ-C30 summary score scale (range 0-100).; Results: Of 948 participants enrolled, 910 (96%) completed baseline questionnaires: 546 with PRR-ROC and 364 with PPS-ROC ≥3. The proportions of participants symptomatic at baseline as per MOST indexes were: abdominal 54%, psychological 53%, and disease- or treatment-related 35%. Improvement was reported in MOST indexes: abdominal 40%, psychological 35%, and disease- or treatment-related 38%. Median time to improvement in abdominal symptoms occurred earlier for PRR-ROC than for PPS-ROC ≥3 (4 vs 6 weeks, p=0.044); median duration of improvement was also similar (9.0 vs 11.7 weeks, p=0.65). Progression-free survival was longer among those with improvement in abdominal symptoms than in those without (median 7.2 vs 2.5 months, p<0.0001). Improvements in HRQL were reported by 77/448 (17%) with PRR-ROC and 61/301 (20%) with PPS-ROC ≥3 (p=0.29), and 102/481 (21%) of those with abdominal symptoms at baseline.; Conclusion: Over 50% of participants reported abdominal and psychological symptoms at baseline. Of those, 40% reported an improvement within 2 months of starting chemotherapy. Approximately one in six participants reported an improvement in HRQL. Symptom monitoring and supportive care is important as chemotherapy palliated less than half of symptomatic participants.; Competing Interests: Competing interests: YCL has received honoraria from GSK for participation on the Advisory Board. FJ acknowledges institutional research grants from GSK and has received honoraria for educational events from AstraZeneca, Astellas, Amgen, BMS, Bayer, Clovis, GSK, Ipsen, MSD, Janssen, Pfizer, and Sanofi. AO acknowledges institutional research grants from MSD K.K., Fuji Pharma, Kissei Pharmaceutical, Meiji Holdings, Taiho Pharmaceutical, Kaken Pharmaceutical, Chugai Pharmaceutical, Tsumura, Daiichi Sankyo, Shinnihonseiyaku, Mochida Pharmaceutical, CMIC Holdings, CMIC Holdings, ASKA Pharmaceutical, Takeda, Pfizer, AstraZeneca, and Terumo; and has received honoraria for educational events from Takeda and AstraZeneca. JL acknowledges institutional research grants from AstraZeneca and MSD/Merck and has received honoraria for educational events from AstraZeneca, Neopharm, GSK and Pfizer and participated on the data safety monitoring board of Regeneron. JS has received honoraria (educational events/travel) from AstraZeneca, Clovis, Clovis and Roche; and has participated on the data safety monitoring board or advisory board for AstraZeneca, Clovis, Eisei, GSK, Novocure, Pfizer, Roche, and Tesaro. MLF acknowledges institutional research grants from AstraZeneca, Novartis, and Beigene; has received honoraria (consultancy/educational events) from AstraZeneca, Novartis, GSK, MSD, Takeda, Lily, and ACT-Genomics; and participated on the data safety monitoring board for AGITG. MTK, RO, AL, FH, AD, FTR, JB, PD, AMO, EA-L, JSB, DB, AF, M-CK, KD and MRS declare no conflict of interest. (© IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Lee Yeonsoo, S., et al. (2022). "Stellate ganglion block as a treatment for vasomotor symptoms: Clinical application." Cleveland Clinic journal of medicine 89(3): 147-153.
	Vasomotor symptoms, also called hot flashes, hot flushes, and night sweats, are common during the menopause transition. Severe symptoms can substantially decrease quality of life. The authors first review current hormonal and nonhormonal therapies, then review evidence supporting the potential use of stellate ganglion block for managing vasomotor symptoms in perimenopausal and postmenopausal women. (Copyright © 2022 The Cleveland Clinic Foundation. All Rights Reserved.)

Lee, Y. J., et al. (2021). "A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01)." Journal of Gynecologic Oncology 32(2): e31.
	BACKGROUND: The optimal treatment of BRCA wild‐type patients with platinum‐sensitive recurrent ovarian cancer remains unknown. Recently, there is an increase in the evidence to support the role of the combination of a poly(adenosine diphosphate‐ribose) polymerase inhibitor, anti‐angiogenic agents, and immunotherapy as maintenance therapy in BRCA wild‐type patients with platinum‐sensitive recurrence. We hypothesized that adding pembrolizumab and bevacizumab to olaparib maintenance can increase progression‐free survival (PFS) in BRCA wild‐type patients with platinum‐sensitive recurrent ovarian cancer. METHODS: BRCA wild‐type patients who received two previous courses of platinum‐containing therapy, achieved complete or partial response to last treatment, and the treatment‐free interval is >6 months after the penultimate platinum‐based chemotherapy offered olaparib maintenance with pembrolizumab and bevacizumab. Forty‐four patients will be included from 4 sites across Singapore and Korea. The primary endpoint of the study is 6‐month PFS rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04361370, Clinical Research Information Service Identifier: KCT0005144.

Lee, Y. K., et al. (2021). "Effects of 16 Weeks of Taekwondo Training on the Cerebral Blood Flow Velocity, Circulating Neurotransmitters, and Subjective Well-Being of Obese Postmenopausal Women." International Journal of Environmental Research and Public Health 18(20).
	We investigated the effects of Taekwondo training on the body composition, serum lipid profiles, plasma neurotransmitter levels, cerebral blood flow velocities, and subjective well‐being of 24 obese postmenopausal women. The women were randomly assigned into the experimental (n = 12) and control (n = 12) groups. The experimental group underwent Taekwondo training five times per week for 16 weeks, while the control group did not. All participants underwent evaluation for the following parameters before and after the intervention: body composition; serum lipid profiles; plasma serotonin and dopamine levels; cerebral blood flow velocities; positive and negative affect schedule (PANAS) scores; satisfaction with life scale (SWLS) scores. After the intervention, it was observed that the weight, body mass index, body fat percentage, total cholesterol, low‐density lip‐oprotein cholesterol, and PANAS‐NA (negative affect in the PANAS questionnaire) scores were significantly decreased (p < 0.05)?while the plasma serotonin levels were significantly increased (p < 0.05)?in the experimental group. Conversely, there were no significant changes in the cerebral blood flow velocities (p > 0.05). Taekwondo training can be effective in not only reducing obesity, but also in increasing the circulating neurotransmitters and enhancing the subjective well‐being of obese postmenopausal women.

Leem, J., et al. (2019). "Herbal medicine (Hyeolbuchukeo-tang or Xuefu Zhuyu decoction) for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials." Medicine 98(5): e14170.
	Background: Primary dysmenorrhea is a condition characterized by painful menstrual cramps that usually occurs in the absence of any identifiable pathological condition among menstruating women, with the prevalence estimates varying between 45% and 95%. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as a standard treatment for primary dysmenorrhea; however, the failure rate of NSAIDs is often 20% to 25% and these drugs commonly cause adverse effects. In this review, we investigated the current evidence related to the effectiveness of Xuefu Zhuyu decoction (XZD) or Hyeolbuchukeo-tang, a traditional herbal formula, as a treatment for primary dysmenorrhea.; Methods: Literature search was conducted about randomized controlled trials (RCTs) for XZD on primary dysmenorrhea. PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Oriental Medicine Advanced Searching Integrated System, and other Chinese, Korean, Japanese databases were searched up to December 20, 2017. Two independent reviewers extracted and assessed the data. The main outcome domains were visual analogue scale (VAS) score and response rate.; Results: Among 475 publications, 8 RCTs involving 1048 patients were finally included. Methodological quality of included RCTs was relatively low. In 4 add-on design studies, XZD plus western medication (WM) group showed better response rate as compared to the WM sole therapy (relative risk 1.18, 95% confidence interval [1.11, 1.25], P < .01). VAS score after the 3rd month of treatment in the XZD plus WM group was also lower than that in the WM group (mean difference -0.45, 95% confidence interval [-0.79, -0.12], P < .01). In 4 XZD versus WM design studies, XZD sole therapy showed better response rate than did WM sole therapy (relative risk 1.26, 95% confidence interval [1.06, 1.49], P < .01).; Conclusion: The existing trials showed a favorable effect of XZD for the management of primary dysmenorrhea. However, the efficacy of XZD on primary dysmenorrhea is not conclusive owing to the small number of studies and the high risk of bias. Large-scale, long-term RCTs with rigorous methodological input are needed to clarify the role of XZD for the management of primary dysmenorrhea.; Trial Registration Number: CRD42016050447 in PROSPERO 2016.

Lei, H., et al. (2022). "The effect of melatonin on hormonal and metabolic outcomes in women with polycystic ovary syndrome (PCOS): a systematic review and meta-analysis."
	
Lei, R., et al. (2021). "Application effect of high-quality nursing model based on hope theory in endometrial cancer patients." Clinical and experimental obstetrics & gynecology 48(3): 691‐696.
	Background: To explore the effect of high‐quality nursing model based on hope theory in endometrial cancer patients. Methods: The patients (n = 120) with endometrial cancer who underwent surgical treatment in hospital from October 2017 to October 2019 were divided into the study group and control group using the random number table method. The patients received usual care in the control group, and received high‐quality nursing based on hope theory in the study group. Then, the degree of pain, fatigue, anxiety and depression were evaluated using visual analogue scale (VAS), chronic pain self‐efficacy scale (CPSS), cancer fatigue scale (RPFS), self‐rating anxiety scale (SAS) and self‐rating depression scale (SDS). The hope level and coping style were assessed using Herth hope scale (HHI) and summary coping style questionnaire (SCSQ). The quality of life was assessed using Medical Outcomes Study item short from health survey (SF‐36). Moreover, nursing satisfaction was compared using homemade questionnaire. Results: The results showed that VAS score, RPFS score, SDS score and passive coping score of SCSQ questionnaire in the study group were lower than those in the control group (p < 0.05). CPSS score, HHI score, positive coping score of SCSQ questionnaire, nursing satisfaction and SF‐36 scores in all dimensions in the study group were higher than those in the control group (p < 0.05). Discussion: The high‐quality nursing model based on hope theory could ameliorate patients' pain and fatigue, enhance their self‐efficacy, guide patients to face problems positively, improve their life quality and hope level. Conclusion: It has higher nursing satisfaction in endometrial cancer.

Lei, W., et al. (2020). "Effects of inositol and alpha lipoic acid combination for polycystic ovary syndrome: A protocol for systematic review and meta-analysis." Medicine 99(30): e20696.
	Background: Polycystic ovary syndrome (PCOS), an intricate and multifactorial disease, has characteristics of diverse clinical, metabolic and endocrine disorder. It represents a primary cause of infertility in reproductive women, which seriously affects the physical and mental health of patients. Several small studies have indicated that inositol and alpha lipoic acid (ALA) supplementation can ameliorate the outcomes in terms of menstrual cyclicity, ovulation and hyperinsulinemia in PCOS women. However, there is a lack of sufficient evidence to affirm this practice. Consequently, we aim to objectively review and estimate the efficacy and safety of inositol plus ALA in adult women suffering from PCOS.; Methods and Analysis: We will retrieve PubMed, EMBASE, The Web of Science, The Cochrane Library of Controlled Trials, Clinical Trials.gov, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wan-Fang database with no specific limitations on language. Simultaneously we will manually retrieve reference lists and grey literature to acquire potential eligibility. We will restrict our search to randomized controlled trials (RCTs) of inositol in combination with ALA for PCOS. Researchers will separately identify studies, extract data and evaluate the quality of studies. We will conduct risk of bias estimates, data synthesis and analysis using Review Manager 5.3 software.; Results and Conclusion: The study will comprehensively determine the effectiveness and safety of inositol conjunct with ALA therapy for PCOS. Meanwhile we intend to disseminate the final findings in a peer-reviewed journal to help patients, clinicians and health policymakers select treatment strategy of PCOS by providing high-quality evidence.

Lei, Y., et al. (2023). "The efficacy and safety of Chinese herbal medicine Guizhi Fuling capsule combined with low dose mifepristone in the treatment of uterine fibroids: a systematic review and meta-analysis of 28 randomized controlled trials." BMC complementary medicine and therapies 23(1): 54.
	Objective: Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the efficacy and safety of GZFL in combination with low-dose mifepristone (MFP) remains controversial.; Materials and Methods: We searched eight literature databases and two clinical trial registries for randomized controlled trials (RCTs) of the efficacy and safety of GZFL combined with low-dose MFP in the treatment of UFs from database inception to April 24, 2022. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. GRADE pro3.6.1 software was used for the assessment of evidence quality.; Results: Twenty-eight RCTs were included in this study, including a total of 2813 patients. The meta-analysis showed that compared with low-dose MFP alone, GZFL combined with low-dose MFP significantly reduced follicle stimulating hormone (p < 0.001), estradiol (p < 0.001), progesterone (p < 0.001), luteinizing hormone (p < 0.001), uterine fibroids volume (p < 0.001), uterine volume (p < 0.001), menstrual flow (p < 0.001) and increased clinical efficiency rate (p < 0.001). Meanwhile, GZFL combined with low-dose MFP did not significantly increase the incidence of adverse drug reactions compared with low-dose MFP alone (p = 0.16). The quality of the evidence for the outcomes ranged from "very low" to "moderate."; Conclusion: This study suggests that GZFL combined with low-dose MFP is more effective and safe in the treatment of UFs, and it is a potential treatment for UFs. However, due to the poor quality of the included RCTs formulations, we recommend a rigorous, high-quality, large-sample trial to confirm our findings. (© 2023. The Author(s).)

Leible, S., et al. (2022). "First-trimester miscarriage rate decreases with hydralazine therapy in pregnancies with early uterine vascular insufficiency: a cohort study." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(25): 6988-6997.
	Background: Miscarriage is the most frequent cause of pregnancy loss, affecting 15-20% of clinically recognized pregnancies. Early uterine vascular insufficiency (EUVI), defined as abnormal uterine artery (UA) Doppler impedance indices in early pregnancy, is present in two-thirds of pregnancies ending in miscarriage after embryonic cardiac activity has been detected. There is currently no available therapy for reducing the risk of miscarriage in these cases.; Objective: To determine whether vasodilator therapy with hydralazine can reduce abnormally high UA impedance indices and miscarriage rates in pregnancies with EUVI when administered from before 9 weeks' gestation until completing 13 weeks' gestation.; Methods: A total of 253 consecutive singleton pregnancies with a live embryo and scanned before 9 weeks' gestation were included in the study. Ninety-two pregnancies (36.3%) were classified as having EUVI. Hydralazine was administered in daily doses of 50 mg, starting 24-36 h after the initial diagnosis of EUVI and continuing throughout the first trimester. The miscarriage rate in the hydralazine-treated EUVI group was compared with the one observed in our previously reported untreated cohort and the pregnancies with EUVI that declined treatment with hydralazine.; Results: The miscarriage rate among the hydralazine-treated EUVI group was significantly lower than the previously reported untreated cohort (7.8% versus 26.2%, p = .003; odds ratio (OR) = 4.3, 95% confidence interval (CI) = 1.6-11.9). In 15 untreated pregnancies with EUVI, the miscarriage rate was similar to that of the previously reported untreated cohort (26.7% versus 26.2%; p = .603) and higher than the hydralazine-treated group (26.7% versus 7.8%, p = .05; OR = 4.4, 95% CI = 1.1-18.2).; Conclusions: Hydralazine therapy in pregnancies with EUVI was associated with a significant decrease in the rate of miscarriage. We suggest a sequence of events leading to a higher risk of miscarriage in pregnancies with EUVI and propose a potential mechanism through which hydralazine may reduce this risk.

Leila, A., et al. (2024). "Safety and efficacy of Neuropelveology for endometriosis management: A systematic review."
	
Leitao Mario, M., et al. (2023). "The RECOURSE Study: Long-term Oncologic Outcomes Associated With Robotically Assisted Minimally Invasive Procedures for Endometrial, Cervical, Colorectal, Lung, or Prostate Cancer: A Systematic Review and Meta-analysis." Annals of surgery 277(3): 387-396.
	Objective: To assess long-term outcomes with robotic versus laparoscopic/thoracoscopic and open surgery for colorectal, urologic, endometrial, cervical, and thoracic cancers.; Background: Minimally invasive surgery provides perioperative benefits and similar oncological outcomes compared with open surgery. Recent robotic surgery data have questioned long-term benefits.; Methods: A systematic review and meta-analysis of cancer outcomes based on surgical approach was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using Pubmed, Scopus, and Embase. Hazard ratios for recurrence, disease-free survival (DFS), and overall survival (OS) were extracted/estimated using a hierarchical decision tree and pooled in RevMan 5.4 using inverse-variance fixed-effect (heterogeneity nonsignificant) or random effect models.; Results: Of 31,204 references, 199 were included (7 randomized, 23 database, 15 prospective, 154 retrospective studies)-157,876 robotic, 68,007 laparoscopic/thoracoscopic, and 234,649 open cases. Cervical cancer: OS and DFS were similar between robotic and laparoscopic [1.01 (0.56, 1.80), P =0.98] or open [1.18 (0.99, 1.41), P =0.06] surgery; 2 papers reported less recurrence with open surgery [2.30 (1.32, 4.01), P =0.003]. Endometrial cancer: the only significant result favored robotic over open surgery [OS; 0.77 (0.71, 0.83), P <0.001]. Lobectomy: DFS favored robotic over thoracoscopic surgery [0.74 (0.59, 0.93), P =0.009]; OS favored robotic over open surgery [0.93 (0.87, 1.00), P =0.04]. Prostatectomy: recurrence was less with robotic versus laparoscopic surgery [0.77 (0.68, 0.87), P <0.0001]; OS favored robotic over open surgery [0.78 (0.72, 0.85), P <0.0001]. Low-anterior resection: OS significantly favored robotic over laparoscopic [0.76 (0.63, 0.91), P =0.004] and open surgery [0.83 (0.74, 0.93), P =0.001].; Conclusions: Long-term outcomes were similar for robotic versus laparoscopic/thoracoscopic and open surgery, with no safety signal or indication requiring further research (PROSPERO Reg#CRD42021240519). (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Leitao, M. M., et al. (2021). "Prophylactic Negative Pressure Wound Therapy After Laparotomy for Gynecologic Surgery: A Randomized Controlled Trial." Obstetrics and Gynecology 137(2): 334-341.
	OBJECTIVE: To estimate the effectiveness of prophylactic negative pressure wound therapy in patients undergoing laparotomy for gynecologic surgery. METHODS: We conducted a randomized controlled trial. Eligible, consenting patients, regardless of body mass index (BMI), who were undergoing laparotomy for presumed gynecologic malignancy were randomly allocated to standard gauze or negative pressure wound therapy. Patients with BMIs of 40 or greater and benign disease also were eligible. Randomization, stratified by BMI, occurred after skin closure. The primary outcome was wound complication within 30 (±5) days of surgery. A sample size of 343 per group (N=686) was planned. RESULTS: From March 1, 2016, to August 20, 2019, we identified 663 potential patients; 289 were randomized to negative pressure wound therapy (254 evaluable participants) and 294 to standard gauze (251 evaluable participants), for a total of 505 evaluable patients. The median age of the entire cohort was 61 years (range 20-87). Four hundred ninety-five patients (98%) underwent laparotomy for malignancy. The trial was eventually stopped for futility after an interim analysis of 444 patients. The rate of wound complications was 17.3% in the negative pressure wound therapy (NPWT) group and 16.3% in the gauze group, absolute risk difference 1% (90% CI -4.5 to 6.5%; P=.77). Adjusted odds ratio controlling for estimated blood loss and diabetes was 0.99 (90% CI 0.62-1.60). Skin blistering occurred in 33 patients (13%) in the NPWT group and in three patients (1.2%) in the gauze group (P<.001). CONCLUSION: Negative pressure wound therapy after laparotomy for gynecologic surgery did not lower the wound complication rate but did increase skin blistering. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02682316. FUNDING SOURCE: The protocol was supported in part by KCI/Acelity.

Leitao, S. and R. Ning (2021). "Exploring the pharmacological mechanism of the effective Chinese medicines on metastatic gynecological tumor based on Meta-analysis combined with network pharmacology analysis."
	
Leite, A. M. C., et al. (2023). "Efficacy of educational instructions on pelvic floor muscle training in the treatment of urinary incontinence: Systematic review and meta-analysis." Neurourology and Urodynamics.
	OBJECTIVE: The present study aimed to investigate the efficacy of educational interventions on pelvic floor (PF) muscle training in the treatment of urinary incontinence (UI). METHODS: This is a systematic review of literature with meta-analysis, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). To do so, randomized clinical trials that performed educational interventions of PF, UI, and developed the training of PF muscles (TPFM) for incontinent women, performing group or individual comparisons, with control and experimental groups or with two or more experimental groups were selected. The search for papers was performed in the following databases: PubMed, Scopus, Embase, Web of Science, and SciELO, no specific publication date was chosen. The risk of bias was performed using the PEDro scale and the quality of the evidence was performed using GRADE. RESULTS: The review included six studies with 1003 participants. Most studies presented 5-8 points regarding risk of bias. Most of the studies were performed in the last 5 years, with women of various ages, high educational level and prevalence of UI of effort. The present study showed that offering educational instructions and guiding women on TPFM was capable of reducing urinary symptoms. When compared to control, significant between-group differences were found in the studies, in which the control group did not receive any kind of instructions or treatment (p < 0.05). The use of technologies through mobile apps was efficient in the treatment of incontinent women (p < 0.05). Performing TPFM individually or in groups did not present differences in the results, with both improving urinary symptoms. The meta-analysis presented a mean effect and a clinically important difference in three studies. CONCLUSION: The interventions involving instructions to TPFM associated to health education brought improvements to urinary symptoms.

Lemos, A. Q., et al. (2019). "The pilates method in the function of pelvic floor muscles: Systematic review and meta-analysis." Journal of Bodywork and Movement Therapies 23(2): 270-277.
	BACKGROUND: Many Pilates instructors believe that the method can produce significant improvement in the resistance of pelvic floor muscles, but it is known that about 49% of women who can contract this muscle do not perform an adequate contraction and cannot increase urethral closure pressure. OBJECTIVES: To evaluate the response of the Pilates method in the function of the pelvic floor muscles, compared to the control group, in healthy women. SEARCH METHODS: The following databases were searched from October to December 2016: PUBMED, SCIELO, LILACS, MEDLINE, WEB OF SCIENCE and CINAHL via PERIÓDICOS CAPES, without restriction of language and year of publication. SELECTION CRITERIA: Randomized (RCTs), quasi-randomized, and non-randomized clinical trials assessing the effectiveness of the Pilates method for the fuction of pelvic floor muscles in healthy women were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the studies, assessed the risk of bias and performed the data extraction. Primary outcomes were the method of evaluation of strength, function, coordination, and symmetry of contraction of the pelvic floor muscles. RESULTS: 4434 articles were identified and 2 articles were selected to compose this review and the meta-analysis. No between-group difference was demonstrated for the pelvic floor muscle function as measured by perineometry (p = 0.32). CONCLUSIONS: No evidence showed a modification of the function of pelvic floor muscles in healthy women practicing the Pilates method.

Lenfant, L., et al. (2023). "Robotic-assisted benign hysterectomy compared with laparoscopic, vaginal, and open surgery: a systematic review and meta-analysis." Journal of Robotic Surgery 17(6): 2647-2662.
	The potential benefits and limitations of benign hysterectomy surgical approaches are still debated. We aimed at evaluating any differences with a systematic review and meta-analysis. PubMed, MEDLINE, and EMBASE databases were last searched on 6/2/2021 to identify English randomized controlled trials (RCTs), prospective cohort and retrospective independent database studies published between Jan 1, 2010 and Dec 31, 2020 reporting perioperative outcomes following robotic hysterectomy versus laparoscopic, open, or vaginal approach (PROSPERO #CRD42022352718). Twenty-four articles were included that reported on 110,306 robotic, 262,715 laparoscopic, 189,237 vaginal, and 554,407 open patients. The robotic approach was associated with a shorter hospital stay (p < 0.00001), less blood loss (p = 0.009), and fewer complications (OR: 0.42 [0.27, 0.66], p = 0.0001) when compared to the open approach. The main benefit compared to the laparoscopic and vaginal approaches was a shorter hospital (R/L WMD: - 0.144 [- 0.21, - 0.08], p < 0.0001; R/V WMD: - 0.39 [- 0.70, - 0.08], p = 0.01). Other benefits seen were sensitive to the inclusion of database studies. Study type differences in outcomes, a lack of RCTs for robotic vs. open comparisons, learning curve issues, and limited robotic vs. vaginal publications are limitations. While the robotic approach was mainly comparable to the laparoscopic approach, this meta-analysis confirms the classic benefits of minimally invasive surgery when comparing robotic hysterectomy to open surgery. We also reported the advantages of robotic surgery over vaginal surgery in a patient population with a higher incidence of large uterus and prior surgery.Copyright © 2023, The Author(s).

Leng, L. L., et al. (2023). "Mindfulness-based intervention for clinical and subthreshold perinatal depression and anxiety: A systematic review and meta-analysis of randomized controlled trial." Comprehensive Psychiatry 122: 152375.
	Objectives: About one in four mothers will experience depression and anxiety during pregnancy and within their first year following childbirth. The meta-analysis aggregated the findings of randomized controlled trials (RCTs) evaluating the immediate post-intervention and maintenance effects of MBI on perinatal depression and anxiety. Method(s): A systematic search was conducted in PubMed, PsycINFO, Medline, Scopus, and Web of Science for English-language journal articles from the first available date until Oct 27th, 2022. Result(s): Twenty-five published RCTs were identified and reviewed, with a total of 2495 perinatal women. MBI was superior to controls for clinical and subthreshold perinatal depression and anxiety. The benefit for depression reduction was stable over time and sustained to the postpartum period, but the maintenance effect on perinatal anxiety was less conclusive. Moreover, MBI's post-intervention effects on depression and anxiety were moderated by perinatal women's symptom severity. The post intervention effects were significantly greater among women in Low- and Middle-Income countries, where perinatal mental health care is less available and accessible. Greater improvement in mindfulness was also associated with a significantly larger post-intervention effect on perinatal depression. Conclusion(s): This meta-analysis suggests that MBIs may complement and extend the available range of effective interventions for clinical and subthreshold perinatal depression and anxiety.Copyright © 2023 The Authors

Lensen, S., et al. (2019). "In vitro fertilization add-ons for the endometrium: it doesn't add-up." Fertility and Sterility 112(6): 987-993.
	The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice. (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Lenycia, N., et al. (2023). "Diet therapies for endometriosis: an umbrella review."
	
Leonardi, M., et al. (2021). "Surgical Interventions for the Management of Chronic Pelvic Pain Syndrome in Women." Journal of Minimally Invasive Gynecology 28(11 Supplement): S69.
	Study Objective: We aimed to review the effectiveness and safety of surgical interventions in the management of patients experiencing chronic pelvic pain syndrome (CPPS), which excluds those with pain known to be caused by i) endometriosis; ii) adenomyosis; iii) primary dysmenorrhoea; iv) active chronic pelvic inflammatory disease; v) irritable bowel syndrome; v) interstitial cystitis/bladder pain syndrome and vi) urethral syndrome. Design(s): We performed a systematic review and meta-analysis for any randomized controlled trials (RCTs) for surgical interventions in patients with CPPS. Each study was independently evaluated by two reviewers for the inclusion and exclusion of trials and extracted data using the forms designed according to the Cochrane guidelines. For each included trial, information was collected regarding method of randomization, allocation concealment, blinding, data reporting and analyses. Setting(s): N/A. Patients or Participants: Female-born patients who had CPPS. Intervention(s): RCTs of surgical interventions in CPPS. Measurements and Main Results: Outcome measures were pain rating scales, quality of life (QoL) measures, and adverse events. 23 studies were identified that were retrieved in full text. A total of four studies met our inclusion criteria. For the primary outcome, the effectiveness of surgical intervention for CPPS as reported by change in pain using validated pain scales, no evidence of benefit was identified for adhesiolysis versus no surgery/diagnostic laparoscopy. Similarly, no evidence of benefit was identified for laparoscopic uterosacral ligament ablation (LUNA) versus diagnostic laparoscopy or vaginal uterosacral ligament resection. No studies were published on the psychological outcomes or requirements for analgesia. Adhesiolysis may improve health related QoL at six months after surgery when compared to diagnostic laparoscopy. Conclusion(s): The currently available information suggests no evidence of benefit for use of adhesiolysis or LUNA in management of pain in those who suffer from CPPS. There may be a QoL benefit to adhesiolysis in improving both the emotional wellbeing and social support, as measured by the validated QoL tools.Copyright © 2021

Leonardi, M., et al. (2020). "When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis." Obstetrical and Gynecological Survey 75(6): 342-344.
	
Leone Roberti, M., et al. (2021). "Fertility-Sparing Treatment of Patients with Endometrial Cancer: A Review of the Literature." Journal of Clinical Medicine 10(20).
	Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3-5% under the age of 40 years. Furthermore, in the last decades a significant shift to pregnancy at older maternal ages, particularly in resource-rich countries, has been observed. Therefore, in this scenario fertility-sparing alternatives should be discussed with patients affected by EC. This study summarizes available literature on fertility-sparing management of patients affected by EC, focusing on the oncologic and reproductive outcomes. A systematic computerized search of the literature was performed in two electronic databases (PubMed and MEDLINE) in order to identify relevant articles to be included for the purpose of this systematic review. On the basis of available evidence, fertility-sparing alternatives are oral progestins alone or in combination with other drugs, levonorgestrel intrauterine system and hysteroscopic resection in association with progestin therapies. These strategies seem feasible and safe for young patients with G1 endometrioid EC limited to the endometrium. However, there is a lack of high-quality evidence on the efficacy and safety of fertility-sparing treatments and future well-designed studies are required.

Lepine, S., et al. (2019). "Advanced sperm selection techniques for assisted reproduction." Cochrane Database of Systematic Reviews(7).
	- Background Assisted reproductive technologies (ART) including in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), combine gametes to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are proposed to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra‐high magnification. These techniques are intended to improve ART outcomes. Objectives To evaluate the effectiveness and safety of advanced sperm selection techniques on ART outcomes. Search methods We conducted a systematic search of electronic databases (Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online, MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL); trials registers (ClinicalTrials.gov, Current Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform); conference abstracts (Web of Knowledge); and grey literature (OpenGrey) for relevant randomised controlled trials (RCTs). We handsearched the reference lists of included studies and similar reviews. The search was conducted in June 2018. Selection criteria We included RCTs comparing advanced sperm selection techniques versus standard IVF, ICSI, or another technique. We excluded studies of intracytoplasmic morphologically selected sperm injection (IMSI), as they are subject to a separate Cochrane Review. Primary outcomes measured were live birth and miscarriage per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned. Secondary adverse events measured included miscarriage per clinical pregnancy and foetal abnormality. Data collection and analysis Two review authors independently assessed study eligibility and risk of bias and extracted data. Any disagreements were resolved by consultation with a third review author. We consulted study investigators to resolve queries. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We combined studies using a fixed‐effect model. We evaluated the quality of the evidence using GRADE methods. Main results We included eight RCTs (4147 women). The quality of evidence ranged from very low to low. The main limitations were imprecision, performance bias, and attrition bias. Hyaluronic acid selected sperm‐intracytoplasmic sperm injection (HA‐ICSI) compared to ICSI Two RCTs compared the effects of HA‐ICSI versus ICSI on live birth. The quality of the evidence was low. There may be little or no difference between groups: 25% chance of live birth with ICSI versus 24.5% to 31% with HA‐ICSI (RR 1.09, 95% CI 0.97 to 1.23, 2903 women, I 2 = 0%, low‐quality evidence). Three RCTs reported on miscarriage. HA‐ICSI may decrease miscarriage per woman randomly assigned: 7% chance of miscarriage with ICSI versus 3% to 6% chance with HA‐ICSI (RR 0.61, 95% CI 0.45 to 0.83, 3005 women, I 2 = 0%, low‐quality evidence) and per clinical pregnancy: 20% chance of miscarriage with ICSI compared to 9% to 16% chance with HA‐ICSI (RR 0.62, 95% CI 0.46 to 0.82, 1065 women, I 2 = 0%, low‐quality evidence). Four RCTs reported on clinical pregnancy. There may be little or no difference between groups: 37% chance of pregnancy with ICSI versus 34% to 40% chance with HA‐ICSI (RR 1.00, 95% CI 0.92 to 1.09, 3492 women, I 2 = 0%, low‐quality evidence). HA‐ICSI compared to SpermSlow One RCT compared HA‐ICSI to SpermSlow. The quality of the evidence was very low. We are uncertain whether HA‐ICSI improves live birth compared to SpermSlow (RR 1.13, 95% CI 0.64 to 2.01, 100 women) or clinical pregnancy (RR 1.05, 95% CI 0.66 to 1.68, 100 women). We are uncertain hether HA‐IC I reduces miscarriage per woman (RR 0.80, 95% CI 0.23 to 2.81, 100 women) or per clinical pregnancy (RR 0.76, 95% CI 0.24 to 2.44, 41 women). Magnetic‐activated cell sorting (MACS) compared to ICSI One RCT compared MACS to ICSI for live birth; three reported clinical pregnancy; and two reported miscarriage. The quality of the evidence was very low. We are uncertain whether MACS improves live birth (RR 1.95, 95% CI 0.89 to 4.29, 62 women) or clinical pregnancy (RR 1.05, 95% CI 0.84 to 1.31, 413 women, I 2 = 81%). We are also uncertain if MACS reduces miscarriage per woman (RR 0.95, 95% CI 0.16 to 5.63, 150 women, I 2 = 0%) or per clinical pregnancy (RR 0.51, 95%CI 0.09 to 2.82, 53 women, I 2 =0) Zeta sperm selection compared to ICSI One RCT evaluated Zeta sperm selection. The quality of the evidence was very low. We are uncertain of the effect of Zeta sperm selection on live birth (RR 2.48, 95% CI 1.34 to 4.56, 203 women) or clinical pregnancy (RR 1.82, 95% CI 1.20 to 2.75, 203 women). We are also uncertain if Zeta sperm selection reduces miscarriage per woman (RR 0.73, 95% CI 0.16 to 3.37, 203 women) or per clinical pregnancy (RR 0.41, 95% CI 0.10 to 1.68, 1 RCT, 62 women). MACS compared to HA‐ICSI One RCT compared MACS to HA‐ICSI. This study did not report on live birth. The quality of the evidence was very low. We are uncertain of the effect on miscarriage per woman (RR 1.52, 95% CI 0.10 to 23.35, 78 women) or per clinical pregnancy (RR 1.06, 95% CI 0.07 to 15.64, 37 women). We are also uncertain of the effect on clinical pregnancy (RR 1.44, 95% CI 0.91 to 2.27, 78 women). Authors' conclusions The evidence suggests that sperm selected by hyaluronic acid binding may have little or no effect on live birth or clinical pregnancy but may reduce miscarriage. We are uncertain of the effect of Zeta sperm selection on live birth, clinical pregnancy, and miscarriage due principally to the very low quality of the evidence for this intervention. We are uncertain of the effect of the other selection techniques on live birth, miscarriage, or pregnancy. Further high‐quality studies, including the awaited data from the identified ongoing studies, are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in routine practice. Plain language summary Advanced sperm selection techniques for assisted reproduction Review question We sought to determine if any advanced sperm selection techniques used for assisted reproduction, except for ultra‐high magnification, alter the rates of live birth, clinical pregnancy, miscarriage, or foetal abnormalities. Background In vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI) is a commonly used treatment for subfertile couples. It is thought that the selection of high‐quality sperm may improve outcomes for these couples. Advanced sperm selection techniques use complex methods to select healthy, mature, and structurally sound sperm for fertilisation. Despite the use of these techniques in many centres worldwide, their effectiveness is unclear. Study characteristics We included eight randomised controlled trials (a type of study in which participants are assigned to one of two or more treatment groups using a random method) with a total of 4147 women. Four studies evaluated sperm selection by their ability to bind to hyaluronic acid during the ICSI process (HA‐ICSI) against ICSI. One study compared HA‐ICSI versus SpermSlow. One study compared HA‐ICSI versus magnetic‐activated cell sorting (MACS) versus ICSI. Three studies compared MACS versus ICSI. One study compared sperm selection by surface charge Zeta potential versus ICSI. Six of the included studies reported rates of live birth; seven reported clinical pregnancy; six reported miscarriage per clinical pregnancy and per woman randomly assigned; and none reported on foetal abnormalities. Key results The current evidence suggests that advanced sperm selection strategies in assisted reproductive technologist (ART) may not result in an inc ease in the like ihood of live birth. The only sperm selection technique that potentially increases live birth and clinical pregnancy rates is Zeta sperm selection, yet these results were of very low quality and derived from a single study, therefore we are uncertain of the effect. There is low‐quality evidence that HA‐ICSI decreases miscarriage rates when compared with ICSI. We are uncertain whether the other sperm selection techniques alter clinical pregnancy or miscarriage rates. No studies reported on foetal abnormalities, and further studies of suitable quality are required before any of these advanced sperm selection techniques can be recommended for use in clinical practice. Evidence quality The evidence gathered was of very low to low quality. The main limitations were imprecision associated with low numbers of participants or events and high risk of performance bias. Data on important clinical outcomes such as foetal abnormalities were absent.

Lequesne, J., et al. (2023). "Evaluation of Scores to Reflect Toxicity Impact on Quality of Life of Patients With Platinum-Resistant Ovarian Cancer: AURELIA Substudy." Journal of the National Comprehensive Cancer Network : JNCCN 21(5): 473.
	Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients' quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation.; Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression.; Results: We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all P<.01), with a weaker association when treatment-related AEs were considered. Global QoL was negatively associated with toxicity scores computed with nonlaboratory all-grade AEs only (β, -3.42 to -3.13; all P<.01). Degrees of association were lower when considering the AE duration.; Conclusions: In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.

Lerma, K., et al. (2021). "Transcutaneous Electrical Nerve Stimulation for Pain Management of Aspiration Abortion up to 83 Days of Gestation: a Randomized Controlled Trial." Obstetrics and Gynecology 138(3): 417‐425.
	OBJECTIVE: To evaluate high‐frequency, high‐intensity transcutaneous electrical nerve stimulation (TENS) as an inexpensive, noninvasive pain management approach for first‐trimester aspiration abortion. METHODS: We conducted a noninferiority, single‐blind, randomized controlled trial of patients seeking aspiration abortion at up to 83 days of gestation. Participants received TENS (placed posteriorly, T10‐L1 and S2‐S4) or intravenous (IV) sedation (fentanyl, midazolam). The primary outcome was pain with aspiration, as self‐reported by visual analog scale (VAS, 100 mm). To detect at least a 15 mm mean difference on the 100 mm VAS with 90% power and a significance level of .05, a total of 90 participants were required. RESULTS: Between January 2018 and October 2019, we enrolled 109 participants (55 TENS, 54 IV). Participant median gestation was 53 days (range 36‐82) in the TENS group and 58 days (range 35‐82) in the IV group (P=.65). Group demographics and clinical histories were similar. Intention‐to‐treat analysis (n=109) yielded noninferior results for the primary outcome (mean difference 4.8 mm, 95% CI ‐5.9 to 13.5 mm). In the per‐protocol analysis, 9 (16%) in the TENS group were excluded after receiving IV sedation; 100 participants were included (46 TENS, 54 IV). Median (range) reported VAS for aspiration was 73 mm (13‐97) and 66 mm (0‐99) in the TENS and IV groups, respectively (P=.40). With a mean difference of 4.4 mm (95% CI ‐5.6 to 14.5 mm), we found TENS to be noninferior to IV. Physicians underestimated participant pain, perceiving pain to be 34 mm (6‐91) in the TENS group and 25 mm (0‐83) in the IV group (P=.003). CONCLUSION: We found TENS to be a noninferior alternative to IV sedation for aspiration pain during first‐trimester abortion. Expanding pain management options can improve quality of and access to abortion. Transcutaneous electrical nerve stimulation could be a standalone or adjunct approach for abortion pain management for those without access to or are ineligible to receive IV sedation due to the lack of sedation practitioner, designated driver, or local restrictions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03187002.

Leshi, M., et al. (2023). "The effect of fertility-sparing therapy with hysteroscopic resection and dydrogesterone for endometrial cancer women: A systematic review and meta‐analysis."
	
Leslie, E. R., et al. (2021). "Building Emotion Awareness and Mental Health (BEAM): Randomized Controlled Trial for Mothers of Children 18-36 Months." ClinicalTrials.gov.
	Maternal mental health symptoms in the first few years following childbirth are common and can have contributed to adverse consequences for both mother and baby. Two of the most common perinatal mental health concerns are depression and anxiety. The COVID-19 pandemic has introduced heightened stressors for families, including physical isolation from support and social networks, additional childcare responsibilities, and economic uncertainty. Unsurprisingly, the pandemic has also led to an increased prevalence of maternal depression and anxiety in Canada and around the world. These mental health problems are associated with increased health problems and low quality of life for mothers. The COVID-19 pandemic has also posed additional challenges to families and mothers with young children are experiencing heightened parenting stress, increasing their support needs. For mothers with depression, these additional parenting stressors can worsen the symptoms and severity their depression. Furthermore, emerging research suggests that the COVID-19 pandemic has had detrimental effects on early child cognitive development. According to the developmental origins of health and disease, exposure to maternal depression in the first 5 years of life is linked to children\'s mental illness, cognitive impairments, and developmental delays. Intervening early is important to help prevent negative long-term consequences for mothers and their children. Without treatment, maternal depressive symptoms tend to remain consistent throughout the preschool years and the adverse consequences of maternal mental health concerns are most pronounced when depression persists. Although there are evidence-based treatments to address maternal mental illness, accessing care can be challenging due to the exceedingly high barriers to service due to COVID-19, such as lack of childcare and time. Web-based resources have been identified as a preference for mental health support by mothers with mental health problems during the perinatal period. Furthermore, mothers have expressed appreciation for peer support during the perinatal period as social support is often highly relied upon in the postnatal period to care for their infants and themselves. Support from other mothers, specifically, has been found to be helpful in recovering from postpartum depression and individuals report higher satisfaction in treatments of postpartum depression that include a peer support component. E-health interventions, designed to target both maternal mental illness and parenting abilities, and that prioritize social support, may be a promising avenue to address the intergenerational impact of perinatal mental health problems. The Building Emotion Awareness and Mental Health (BEAM) program is an app-based and online group therapy program that was developed to respond to the high needs of mothers managing depression, anxiety, and parenting stress. There are 3 objectives for this study: Evaluate the efficacy of the BEAM app-based program for improving depression compared to a treatment as usual (TAU) control group. Examine the benefits of BEAM for family relationships, anxiety, parenting stress and behaviours, and child functioning. Examine exploratory outcomes of parent-child relationship quality, maternal sensitivity, and child emotional reactivity.

Lete, I. (2022). "Aromatase inhibitors in the treatment of endometriosis-associated pelvic pain: A systematic review." Clinica e Investigacion en Ginecologia y Obstetricia 49(1): 100706.
	Objective: To know the effect of the use of aromatase inhibitors (AI) in the treatment of endometriosis-associated pelvic pain (EAPP). Material(s) and Method(s): Systematic review of the literature. Result(s): 173 articles were identified of which 25 were valid for the review, of which 4 were randomized clinical trials, 3 were non-randomized clinical trials, 10 were prospective non-comparative studies and 8 were clinical case reports. In most of the studies and/or case reports (24 of 27) the use of AI was associated with an improvement in EAPP. Important biases were identified that may influence the efficacy analysis, primarily the combined use of AI with other drugs widely used in the treatment of endometriosis. Conclusion(s): Despite the existence of numerous articles presenting and/or analysing the effect of AIs in the control of EEAP, the biases in the interpretation of their results, together with the side effect profile of this group of drugs, mean that their use has not become widespread, and they continue to be considered an experimental treatment for endometriosis. To date, there is insufficient evidence of sufficient quality to recommend the use of AI in the treatment of EEAP in routine clinical practice.Copyright © 2021 Elsevier Espana, S.L.U.

Lete, I., et al. (2021). "The use of menopausal hormone therapy in women survivors of gynecological cancer: Safety report based on systematic reviews and meta-analysis." European Journal of Gynaecological Oncology 42(5): 1058-1067.
	The data collected during the last two decades on the effects of Hormonal menopause treatment (HMT) could help to provide a safer and more effective long term-treatment of menopause symptoms and possible complications such as osteoporotic fractures, cognitive impairment, or cardiovascular conditions, as well as an improved quality of life. Having a history of suffering from gynecological cancer (endometrial, cervical or ovarian) is one of the conditions that most strongly determines the use of any form of HMT due to the concerns associated with a possible recurrence of the disease. Objective(s): To create a set of eligibility criteria for the use of HMT in gynecological cancer patients. Method(s): The study was registered in PROSPERO (registration number CRD42020166658). Result(s): Ovarian cancer survivors who use HMT have better overall survival, disease-free survival, and lower recurrence rates than women survivors who do not use HMT. Endometrial cancer survivors who use HMT do not have a higher rate of disease recurrence than those survivors who do not use HMT. Cervical cancer survivors who use HMT do not have a higher rate of disease recurrence than those survivors who do not use HMT. Conclusion(s): HMT is safe in women who have suffered from most of non-advanced gynecological cancers.Copyright ©2021 The Author(s).

Leung, E., et al. (2022). "Quality-of-Life Outcomes and Toxic Effects Among Patients With Cancers of the Uterus Treated With Stereotactic Pelvic Adjuvant Radiation Therapy: The SPARTACUS Phase 1/2 Nonrandomized Controlled Trial." JAMA Oncology 8(6): 1-9.
	Importance: Adjuvant radiation plays an important role in reducing locoregional recurrence in patients with uterine cancer. Although hypofractionated radiotherapy may benefit health care systems and the global community while decreasing treatment burden for patients traveling for daily radiotherapy, it has not been studied prospectively nor in randomized trials for treatment of uterine cancers, and the associated toxic effects and patient quality of life are unknown.; Objective: To evaluate acute genitourinary and bowel toxic effects and patient-reported outcomes following stereotactic hypofractionated adjuvant radiation to the pelvis for treatment of uterine cancer.; Design, Setting, and Participants: The Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS) phase 1/2 nonrandomized controlled trial of patients accrued between May 2019 and August 2021 was conducted as a multicenter trial at 2 cancer centers in Ontario, Canada. In total, 61 patients with uterine cancer stages I through III after surgery entered the study.; Interventions: Stereotactic adjuvant pelvic radiation to a dose of 30 Gy in 5 fractions administered every other day or once weekly.; Main Outcomes and Measures: Assessments of toxic effects and patient-reported quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and endometrial EN24) were collected at baseline, fractions 3 and 5, and at 6 weeks and 3 months of follow-up. Descriptive analysis was conducted, calculating means, SDs, medians, IQRs, and ranges for continuous variables and proportions for categorical variables. Univariate generalized linear mixed models were generated for repeated measurements on the quality-of-life scales.; Results: A total of 61 patients were enrolled (median age, 66 years; range, 51-88 years). Tumor histologic results included 39 endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 dedifferentiated. Sixteen patients received sequential chemotherapy, and 9 received additional vault brachytherapy. Median follow-up was 9 months (IQR, 3-15 months). Of 61 patients, worst acute gastrointestinal tract toxic effects of grade 1 were observed in 33 patients (54%) and of grade 2 in 8 patients (13%). For genitourinary worst toxic effects, grade 1 was observed in 25 patients (41%) and grade 2 in 2 patients (3%). One patient (1.6%) had an acute grade 3 gastrointestinal tract toxic effect of diarrhea at fraction 5 that resolved at follow-up. Only patient-reported diarrhea scores were both clinically (scores ≥10) and statistically significantly worse at fraction 5 (mean [SD] score, 35.76 [26.34]) compared with baseline (mean [SD] score, 6.56 [13.36]; P < .001), but this symptom improved at follow-up.; Conclusions and Relevance: Results of this phase 1/2 nonrandomized controlled trial suggest that stereotactic hypofractionated radiation was well tolerated at short-term follow-up for treatment of uterine cancer. Longer follow-up and future randomized studies are needed to further evaluate this treatment.; Trial Registration: ClinicalTrials.gov Identifier: NCT04866394.

Leung, E. W., et al. (2021). "Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS): A Multicenter Prospective Trial Evaluating Acute Toxicities and Patient Reported Outcomes." International Journal of Radiation Oncology, Biology, Physics 111(3S): S18-S19.
	PURPOSE/OBJECTIVE(S): Adjuvant radiation plays a significant role in reducing locoregional recurrences in uterine cancers. Standard treatment consists of daily radiation for 5 weeks which can be challenging for patients and the healthcare system, especially during the COVID pandemic. Hypofractionated radiotherapy has been evaluated and established in other pelvic malignancies. This study aims to evaluate the acute urinary and bowel toxicities, and patient reported outcomes following stereotactic hypofractionated adjuvant radiation for endometrial cancer. MATERIALS/METHODS: This is a prospective phase I/II trial in which patients with endometrial cancer planned for adjuvant radiation received 30 Gy in 5 fractions, every other day or once weekly. Treatment was delivered at two centers with volumetric arc radiation therapy with a body-vacuum immobilization, bowel enema and 3D image-guidance. Toxicity assessment, outcomes and patient reported quality of life (QOL, EORTC core QLQ-C30 and endometrial EN24) were collected at baseline, fractions (F) 3 and 5, and at regular follow-up intervals. Higher scores represent better global QOL/health status or worse symptoms (scale 0 - 100). Changes in QOL over time were investigated with linear mixed-effects models. A P-value threshold of 0.05 was used for statistical significance. A change in QOL score of ≥ 10 points was considered clinically significant. RESULTS: The median age of the 41 enrolled patients is 66 (range: 51 - 88). Histologies included 29 endometrioid adenocarcinoma, 8 serous/clear cell, 1 carcinosarcoma, and 3 dedifferentiated. Thirty patients had stage 1 disease while 3 had stage 2 and 8 stage 3. Seven patients received sequential chemotherapy and 3 had additional vault brachytherapy. Median follow-up is 9 months, with worst toxicity (GI or GU) of grade 1 and 2 in 63% and 24% respectively. No patients have experienced a grade 3 or higher toxicity. Patient-reported diarrhea and gastrointestinal domain scores were statistically significantly worse than baseline at F5 (mean paired difference = 27.2; 8.7, P < .005) and 6 weeks (mean paired difference = 7.9; 5.1, P < 0.05), and returned to baseline levels at 12 weeks (Table 1). The only clinically significant change (≥ 10) from baseline was in diarrhea at F5. There were no significant changes in urinary domain, overall health and quality of life scores. No locoregional recurrences have been found; 3 patients recurred distantly, of which 2 died of metastatic disease. CONCLUSION: Stereotactic hypofractionated radiation for uterine cancers is feasible and well-tolerated with short-term follow-up. Longer follow-up and future randomized studies are needed to further evaluate this treatment.

Leung John, H., et al. (2022). "Cost-effectiveness analysis of olaparib and niraparib as maintenance therapy for women with recurrent platinum-sensitive ovarian cancer." Expert review of pharmacoeconomics & outcomes research 22(3): 489-496.
	Objective: We evaluated the cost-effectiveness of olaparib and niraparib as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer. Methods: A decision analysis model compared the costs and effectiveness of olaparib and niraparib versus placebo for patients with or without germline BRCA mutations. Resource use and associated costs were estimated from the 2020 National Health Insurance Administration reimbursement price list. Clinical effectiveness was measured in progression-free survival per life-years (PFS-LY) based on the results of clinical trials SOLO2/ENHOT-Ov21 and ENGOT-OV16/NOVA. The incremental cost-effectiveness ratio (ICER) was estimated from a single-payer perspective.; Results: In the base case, olaparib was the more cost-effective treatment regimen. The ICERs for olaparib and niraparib compared to placebo were NT$1,804,785 and NT$2,340,265 per PFS-LY, respectively. Tornado analysis showed that PFS and the total resource use cost of niraparib regimen for patients without gBRCA were the most sensitive parameters impacting the ICER. The ICERs for both drugs in patients with a gBRCA mutation were lower than in patients without a gBRCA mutation. Probabilistic sensitivity analysis indicated that olaparib was more cost-effective than niraparib at the willingness-to-pay threshold of NT$2,602,404 per PFS life-year gained.; Conclusion: Olaparib was estimated to be less cost and more effective compared to niraparib as maintenance therapy for patients with recurrent platinum-sensitive ovarian cancer.

Levesque, A., et al. (2021). "Botulinum toxin infiltrations versus local anaesthetic infiltrations in pelvic floor myofascial pain: Multicentre, randomized, double-blind study." Annals of Physical and Rehabilitation Medicine 64(1): 101354.
	BACKGROUND: Many studies have demonstrated a link between pelvic floor myofascial syndromes and chronic pelvic pain. Botulinum toxin has been extensively used for several years in the field of pain, especially due to its action on muscle spasm. However, the efficacy of botulinum toxin in the context of chronic pelvic pain remains controversial. OBJECTIVES: This multicentre, randomized, controlled, double-blind study was designed to compare the efficacy of botulinum toxin and local anaesthetic (LA) injection versus LA injection alone for pelvic floor myofascial syndrome and chronic pelvic pain. METHODS: According to the number of painful trigger points detected on physical examination, patients received from 1 to 4 injections of botulinum toxin with LA (BTX) or LA alone. The primary endpoint was Patient Global Impression of Improvement (PGI-I) score on day 60 after infiltration. Secondary endpoints were pain intensity, number of painful trigger points on palpation, analgesic drug consumption and quality of life. RESULTS: We included 80 patients, 40 in each group. This study failed to demonstrate a significant difference between the 2 groups on day 60 in the primary endpoint or secondary endpoints (PGI-I score≤2=20% [LA] versus 27.5% [BTX], P=0.43). However, both groups showed significant alleviation of global pain. CONCLUSION: This study does not justify the use of botulinum toxin in the context of chronic pelvic pain with myofascial syndrome but does justify muscle injections with LA alone. ClinicalTrials.gov: NCT01967524.

Levi, S., et al. (2021). "One step further: randomised single-centre trial comparing the direct and afterload techniques of embryo transfer." Human reproduction (Oxford, England) 36(9): 2484-2492.
	STUDY QUESTION: What are the differences in ease of use between two different embryo transfer (ET) techniques: the preload direct approach and the afterload approach. SUMMARY ANSWER: The afterload technique seems to reduce the rate of difficult ETs. WHAT IS KNOWN ALREADY: Numerous published trials now document that the ET procedure has an impact on pregnancy and delivery rates after IVF. Difficult transfers should be avoided, as they reduce implantation and pregnancy rates. Preload direct ETs with soft catheters under ultrasound guidance is currently considered the best procedure. However, when using soft catheters, it is not known which technique is preferable or which one should be implemented to reduce the operator factor. STUDY DESIGN, SIZE, DURATION: This prospective randomised unblinded controlled clinical trial, included 352 ultrasound-guided ETs assigned to either direct ET or afterload ET, between September 2017 and March 2019. The sample size was calculated based on the historical rate of difficult ETs encountered between 2014 and 2015 with a direct ET procedure. PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criteria were women 18-38 years old, with BMI between 18 and 28, receiving a single-thawed blastocyst transfer. The exclusion criteria were use of testicular sperm and preimplantation genetic testing (PGT) cycles. The primary outcome was the rate of difficult or suboptimal transfers defined as: advancement of the outer sheath (specific for the direct transfer), multiple attempts, use of force, required manipulation, use of a stylet or tenaculum, dilatation, or use of a different catheter. The secondary outcome was clinical pregnancy rate. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 352 frozen ETs were randomised, with 176 patients in each group. The two arms were homogeneous for female and male age, female BMI, duration of infertility, secondary infertility, previous deliveries or miscarriages, myomas, previous surgery to the uterine cavity, cycle day at ovulation trigger, freeze all cycles, first transfers, indication for treatment, endometrial preparation protocol and duration, endometrial thickness, and blastocyst grade at vitrification. Across the entire population, 85 (24.1%) ETs were defined as difficult. The rate of difficult transfers was significantly higher in the direct ET group than in the afterload group: 68 (38.6%) versus 17 (9.7%), respectively (OR 0.17, 95% CI 0.09-0.30, P < 0.001). The mean percentage in the rate of difficult transfers per operator was 22.5% (SD ± 14.5%), of which 36.1% (SD ± 23.4%) were in the direct group compared with 8.6% (± 8.2%) in the afterload group (P < 0.001). The difficult transfer rate among operators varied from 0 to 43.8% (0-77.8% in the direct group and 0 to 25.0% in the afterload group). The clinical pregnancy rates (42.0% vs 48.3%, P = 0.239 in the direct and afterload groups, respectively) were not significantly different between the groups. LIMITATIONS, REASONS FOR CAUTION: There were 18 experienced operators who participated in the trial. Conclusions about the pregnancy rate should not be generalised, since the sample analysis was not performed on this outcome and, although clinically relevant, the difference was not significantly different. WIDER IMPLICATIONS OF THE FINDINGS: The rate of difficult transfers was significantly higher in the direct ET group compared with the afterload ET group, although a wide variation was observed among operators. Further studies regarding the association between transfer technique and ART outcomes are required. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought and there are no competing interests. TRIAL REGISTRATION NUMBER: NCT03161119. TRIAL REGISTRATION DATE: 5 April 2017. DATE OF FIRST PATIENT'S ENROLMENT: 26 September 2017.

Levit, E., et al. (2024). "A Systematic Review of Autoimmune Oophoritis Therapies." Reproductive Sciences 31(1): 1-16.
	Autoimmune primary ovarian insufficiency (POI) is a devastating disease with limited clinical guidance. The objective of this systematic review was to identify treatments for autoimmune POI and analyze their efficacy. A comprehensive search of CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science was performed from inception to April 2022. English language publications that evaluated women with autoimmune POI after a documented intervention were included. Animal models of autoimmune POI were also included. Risk of bias was assessed with the SYRCLE's risk of bias tool for animal studies or the NIH Quality Assessment Tool for Case Series as appropriate. Twenty-eight studies were included in this review, with 11 RCTs, 15 case reports, and 2 case series. Seventeen studies were in humans, and 11 were in animal models. No completed RCTs, cohort studies, or case-control studies were identified in humans. In observational human studies, corticosteroids were effective in select patients. In many case reports, adequate treatment of comorbid autoimmune conditions resulted in return of menses, hormonal normalization, or spontaneous pregnancy. In terms of assisted reproductive technologies, there was case report evidence for both in vitro fertilization (IVF) and in vitro maturation (IVM) in women wishing to conceive with their own oocytes. Ovulation induction, IVF, and IVM resulted in a total of 15 pregnancies and 14 live births. In animal models, there was additional evidence for stem cell therapies and treatments used in traditional Chinese medicine, although this research may not be generalizable to humans. Furthermore, litter size was not evaluated in any of the animal studies. Additional research is needed to establish the efficacy of current treatments for autoimmune POI with a controlled experimental design and larger sample size. Additionally, there is a critical need to develop novel therapies for this condition, as understanding of its pathophysiology and available tools to modulate the immune response have progressed.Copyright © 2023, The Author(s), under exclusive licence to Society for Reproductive Investigation.

Levy, G., et al. (2022). "Surgical treatment of advanced anterior wall and apical vaginal prolapse using the anchorless self-retaining support implant: long-term follow-up." International Urogynecology Journal 33(11): 3067-3075.
	Introduction and Hypothesis: Following health notification by the FDA in 2008 of serious complications with transvaginal mesh for anterior pelvic organ prolapse, there has been a return to native tissue repairs. Earlier work with a self-retaining support (SRS) implant showed a high anatomical success rate with minimal implant-related complications over a medium-term follow-up. It is proposed that post-implant complications are more a consequence of the method of mesh anchoring rather than the implant itself. Our system incorporates an ultralight mesh with a frame that provides level I, II, and III support without the need for fixation. The first long-term outcomes of SRS implantation are presented.; Methods: A prospective multicenter trial was conducted using two consecutive identical protocols of the use of the SRS implant in women with symptomatic anterior compartment prolapse extending their follow-up to 36 months. Anatomical success (Pelvic Organ Prolapse Quantification stage 0 or 1 or a Ba ≤ -2) was recorded along with subjective success as defined by regular quality-of-life (PFDI-20 and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire) assessments.; Results: Sixty-seven patients completed 36 months of follow-up. Mean Ba measurements improved from 3.1 (-1 to 6) cm to -2.8 (-1 to -3) cm and C point from 0.4 (-8 to 6) cm to -6.9 (-10 cm to 1) cm. accumulating to a significant anatomical success rate of 94.3%. Subjective success based on question #3 of the PFDI-20, analyzed for the index surgical compartment, reached 95.7%. Post-operative complications included 2 cases of urinary retention, 1 minor frame exposure, 1 case of delayed voiding dysfunction, and 2 cases of de novo stress urinary incontinence. Untreated pre-operative second-degree Bp measurements had increased in 27% at follow-up.; Conclusion: The long-term outcome of the SRS implant shows an excellent subjective and objective success with minimal risk of complications or need for reintervention. (© 2021. The International Urogynecological Association.)

Lewkowitz, A. K., et al. (2023). "The effect of digital health interventions for postpartum depression or anxiety: a systematic review and meta-analysis of randomized controlled trials." American Journal of Obstetrics and Gynecology.
	OBJECTIVE: To examine the effect of digital health interventions (DHIs) compared to treatment as usual (TAU) on preventing and treating postpartum depression (PPD) and postpartum anxiety (PPA). DATA SOURCES: Searches in Ovid Medline, Embase, SCOPUS, Cochrane Database, and ClinicalTrials.gov for randomized controlled trials comparing DHIs to TAU for preventing or treating PPD and PPA. The primary outcome was the score on the first ascertainment of PPD or PPA symptoms after the intervention. Secondary outcomes included screening positive for PPD or PPA-as defined in the primary study-and loss to follow-up, defined as the proportion of participants who completed the final study assessment compared to the number who were initially randomized. METHODS OF STUDY SELECTION: Two authors independently screened all abstracts for eligibility and independently reviewed all potentially eligible full-text articles for inclusion. A third author screened abstracts and full-text articles as needed to determine eligibility in cases of discrepancy. For continuous outcomes, the Hedges method was used to obtain standardized mean differences (SMD) when the studies used different psychometric scales, and weighted mean differences (WMD) were calculated when studies used the same psychometric scales. For categorical outcomes, pooled relative risks (RR) were estimated. TABULATION, INTEGRATION, AND RESULTS: Of 921 studies originally identified, 31 randomized controlled trials-corresponding to 5,532 participants randomized to DHI and 5,492 participants randomized to TAU-were included. Compared to TAU, DHIs significantly reduced mean scores ascertaining PPD symptoms (29 studies: SMD -0.64 (95% Confidence Interval (CI): -0.88, -0.40), I2= 94.4%) and PPA symptoms (17 studies: SMD -0.49 (95% CI: -0.72, -0.25) ), I2= 84.6%). In the few studies that assessed screen-positive rates for PPD (n=4) or PPA (n=1), there was no significant differences between those randomized to DHI versus TAU. Overall, those randomized to DHI had 38% increased risk of not completing the final study assessment compared to those randomized to TAU (pooled RR 1.38 (95% CI 1.18, 1.62), but those randomized to app-based DHI had similar loss-to-follow-up rates as those randomized to TAU (RR 1.04 (95% Confidence Interval: 0.91, 1.19)). CONCLUSION: DHIs modestly, but significantly, reduced scores assessing PPD and PPA symptoms. More research is needed to identify DHIs that effectively prevent or treat PPD and PPA but encourage ongoing engagement throughout the study period.

Leyland, N., et al. (2019). "Ndegree 244 - Endometriose: Diagnostic et prise en charge (resume/declarations sommaires et recommandations)." Journal of Obstetrics and Gynaecology Canada 41(Supplement 1): S146-S150.
	Objectif: Ameliorer la comprehension de l'endometriose et fournir une directive clinique factuelle pour ce qui est du diagnostic et de la prise en charge de l'endometriose. Issues: Parmi les issues evaluees, on trouve les effets de la prise en charge medicale et chirurgicale de l'endometriose sur la morbidite et l'infertilite que connaissent les femmes. Methodes: Les membres du comite voue a la presente directive clinique ont ete selectionnes en fonction de leur expertise respective, et ce, en vue de representer une gamme d'experiences pratiques et universitaires tant au niveau de la representation geographique au Canada que du type de pratique (nous avons egalement cherche a nous assurer de representer l'expertise des sous-specialites et l'experience en gynecologie generale). Le comite a analyse toutes les donnees disponibles issues de la litterature medicale (en anglais et en francais), ainsi que les donnees disponibles issues d'un sondage mene aupres de Canadiennes. Les recommandations ont ete formulees sous forme de declarations de consensus. Le document final a ete analyse et approuve par le comite executif et le Conseil de la Societe des obstetriciens et gynecologues du Canada. Resultats: Le present document offre un resume des derniers resultats en ce qui concerne le diagnostic, les explorations et la prise en charge medicale et chirurgicale de l'endometriose. Les recommandations qui en resultent peuvent etre adaptees par chacun des fournisseurs de soins de sante offrant ses services a des femmes qui presentent cette pathologie. Conclusion(s): L'endometriose est une pathologie courante et parfois debilitante qui affecte les femmes en age de procreer. Une approche multidisciplinaire mettant en jeu une combinaison de modifications du mode de vie, de medicaments et de services paramedicaux devrait etre utilisee pour limiter les effets de cette pathologie sur les activites de la vie quotidienne et la fertilite. Dans certaines circonstances, le recours a la chirurgie s'avere necessaire pour confirmer le diagnostic et fournir un traitement cherchant a atteindre l'objectif vise en matiere de soulagement de la douleur ou d'amelioration de la fertilite. Les femmes qui obtiennent une strategie acceptable de prise en charge de cette pathologie peuvent connaitre une amelioration de leur qualite de vie ou atteindre leur objectif quant a l'obtention d'une grossesse reussie. Donnees: Des recherches ont ete menees dans les bases de donnees Medline et Cochrane en vue d'en tirer les articles publies, en anglais et en francais, entre janvier 1999 et octobre 2009 sur les sujets lies a l'endometriose, a la douleur pelvienne et a l'infertilite, et ce, en vue de la redaction d'une directive clinique de consensus canadienne sur la prise en charge de l'endometriose. Valeurs: La qualite des resultats a ete evaluee au moyen des criteres decrits par le Groupe d'etude canadien sur les soins de sante preventifs. Les recommandations quant a la pratique ont ete classees en fonction de la methode decrite par le groupe d'etude. Reportez-vous au Tableau 1. Avantages, desavantages et couts: La mise en oeuvre des recommandations de la presente directive clinique entrainera l'amelioration des soins offerts aux femmes dont les douleurs et l'infertilite sont associees a l'endometriose.Copyright © 2019

Leziak, M., et al. (2022). "Future Perspectives of Ectopic Pregnancy Treatment-Review of Possible Pharmacological Methods." International Journal of Environmental Research and Public Health 19(21).
	Ectopic pregnancy, that is, a blastocyst occurring outside the endometrial cavity of the uterus, affects nearly 2% of pregnancies. The treatment of ectopic pregnancy is surgical or pharmacological. Since surgical management is associated with numerous serious side effects, conservative treatment is sought. The treatment of choice in the majority of cases is based on pharmacotherapy with methotrexate (MTX) in a single- or multi-dose regimen. Although the efficacy of methotrexate reaches between 70 and 90%, its use requires specific conditions regarding both the general condition of the patient and the characteristic features of the ectopic pregnancy. Moreover, MTX can cause severe adverse effects, including stomatitis, hepatotoxicity and myelosuppression. Therefore, clinicians and researchers are still looking for a less toxic, more effective treatment, which could prevent surgeries as a second-choice treatment. Some studies indicate that other substances might constitute a good alternative to methotrexate in the management of ectopic pregnancies. These substances include aromatase inhibitors, especially letrozole. Another promising substance in EP treatment is gefitinib, an inhibitor of EGFR tyrosine domain which, combined with MTX, seems to constitute a more effective alternative in the management of tubal ectopic pregnancies. Other substances for local administration include KCl and absolute ethanol. KCl injections used in combination with MTX may be used when foetal heart function is detected in cervical ectopic pregnancies, as well as in heterotopic pregnancy treatment. Absolute ethanol injections proved successful and safe in caesarean scar pregnancies management. Thus far, little is known about the use of those substances in the treatment of ectopic pregnancies, but already conducted studies seem to be promising.

L'Hermite, M. (2022). "BIJUVA, the only bioidentical HRT, combining estradiol and progesterone in a single pill: finally available in Belgium, after the USA (approval in 2018 by the Food and Drug Administration) !" Revue Medicale de Bruxelles 43(3): 244-247.
	Bijuva is intended for the <> treatment of estrogen deficiency symptoms. It combines the two bioidentical female hormones (progesterone P4 and estradiol E2) in low doses into a single capsule. It is taken in the evening, promoting falling asleep and improving sleep disorders. The phase 3 trial, REPLENISH, randomized double-blind versus placebo-controlled, demonstrated good effectiveness on vasomotor symptoms and quality of life, as well as, over one year, its endometrial safety (no endometrial hyperplasia). Bijuva is a non-stop continuous combination drug that minimizes blood loss and results in 90% amenorrhea at one year. It is metabolically neutral (blood glucose and cholesterol) and even beneficial in women who started it early, namely less than 6 years after menopause. Bijuva does not affect weight or blood pressure. Despite its oral intake, it does not increase the coagulation parameters, indicating a possible neutrality on thromboembolic risk in the absence of thrombophilia or high-risk factors. In one year, Bijuva did not increase the percentage of abnormal mammograms (Bi-Rads 3 + 4) but significantly increased the incidence of breast tenderness (10.8%). Finally, Bijuva improved bone-remodeling markers, indicating a good probability of a preventive effect of osteoporotic fractures, similar to other HRT (hormonal replacement treatments). The availability of a bioidentical HRT, combining estradiol and progesterone in a single capsule, will certainly improve compliance and help promoting HRT rehabilitation through a neutral metabolic and oncology profile.Copyright © 2022 Association des Medecins anciens etudiats de l'Universite libre de Bruxelles (A.M.U.B.). All rights reserved.

Li, B., et al. (2021). "Efficacy and safety of current therapies for genitourinary syndrome of menopause: A Bayesian network analysis of 29 randomized trials and 8311 patients." Pharmacological research 164: 105360.
	Genitourinary syndrome of menopause (GSM) seriously affects the quality of life of women in this stage and patients with breast cancer, but optimal treatment options as well as risks associated with the complication remain controversial. We aimed at exploring the safest and most effective treatment for genitourinary syndrome of menopause. The study was performed following a pre-established protocol registered on PROSPERO (CRD42020180807). We searched through PubMed, Embase, Scopus, Cochrane Library, Web of Science and ScienceDirect electronic databases, clinicaltrials.gov and OVID for relevant data on Genitourinary syndrome of menopause provided by March 2020. Randomised controlled trials (RCTs) on women presenting with some or all the signs and symptoms for genitourinary syndrome of menopause were extracted and analyzed based on the Bayesian theory. The key variables were additionally evaluated using the network sub-analyses, standard pairwise comparisons, regression analysis and subgroup and sensitivity analyses. The pooled estimates were quantified as odd ratios or mean differences where appropriate, at 95 % confidence intervals. In the end, 29 randomized controlled trials (RCTs) evaluating 5 different treatment regimens for genitourinary syndrome of menopause, involving 8311 patients, were included in the study. Laser therapy had excellent effect on vaginal dryness, dysparunia, urinary incontinence, proportion of parabasal cells, pH and VHI. Vaginal estrogen also had significant effects on these aspects, although its effect was inferior to that of laser therapy. Ospemifene therapy was however superior to laser and vaginal estrogen therapies in ameliorating sexual function, however, it presents a high risk of developing adverse events and endometrial hyperplasia. Moisturizer/lubricant was effective on dysparunia, proportion of parabasal cells and vaginal pH. In regression analysis, age was an essential factor affecting vaginal dryness and pH treatment effect. Compared with other currently available interventional treatments for genitourinary syndrome of menopause, laser therapy, followed by vaginal estrogen, confers superior clinical outcomes for most aspects associated with the disease. In addition, they pose relatively low risks of developing adverse events. Ospemifene and DHEA therapies on their part significantly improve sexual function of women with GSM. A strong relationship between treatment effect and age provides insights for future studies on clinical treatment. (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Li, C., et al. (2023). "Combinational use of trabectedin and pegylated liposomal doxorubicin for recurrent ovarian cancer: a meta-analysis of phase III randomized controlled trials." American journal of translational research 15(12): 6675-6689.
	Background: In recent years, pegylated liposomal doxorubicin (PLD) has been widely used to improve the survival of patients with ovarian cancer; however, it is unclear whether the combinational use of PLD with other drugs is more effective. Therefore, this meta-analysis aimed to confirm the efficacy and safety of trabectedin, combined with PLD, in the treatment of recurrent ovarian cancer.; Methods: Data corresponding to all eligible clinical trials as of May 15, 2022, was retrieved using several electronic retrieval databases including PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), ClinicalTrials.gov, Excerpta Medica Database (EMBASE) and Cochrane Library clinical controlled trials (CENTRAL). Comprehensive hazard ratios (HRs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using the Review Manager software 5.4 (RevMan 5.4).; Results: From two phase III randomized controlled trials, 1248 patients with recurrent ovarian cancer were included in this meta-analysis. Results of meta-analysis revealed that trabectedin, combined with PLD chemotherapy, significantly improved overall survival (OS) in patients with BReast CAncer gene ( BRCA )-associated recurrence (HR, 0.49; 95% CI, [0.33-0.73]; P = 0.0004) and platinum-sensitive recurrence whose platinum-free interval (PFI) was 6-12 months (HR, 0.66; 95% CI, [0.52-0.84]; P = 0.0005). In addition, compared with PLD alone, combination therapy significantly improved the progression-free survival (PFS) in patients with recurrent ovarian cancer (HR, 0.86; 95% CI, [0.74-0.99]; P = 0.03). Combination therapy also significantly improved PFS in patients with BRCA -associated recurrence (HR, 0.58; 95% CI, [0.40-0.58]; P = 0.004), and platinum-sensitive recurrence (HR, 0.73; 95% CI, [0.56-0.95]; P = 0.02). Trabectedin combined with PLD was more prone to grade 3-4 toxic side effects than PLD alone ( P < 0.05); however, fatal adverse events related to non-toxic side effects occurred.; Conclusion: Trabectedin combined with PLD significantly improves OS and PFS in patients with BRCA -associated and platinum-sensitive recurrent ovarian cancers. The potential use of trabectedin combined with PLD should be selected according to the PFI and BRCA mutation status of patients.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (AJTR Copyright © 2023.)

Li, D., et al. (2021). "Changes in thyroid function during controlled ovarian hyperstimulation (COH) and its impact on assisted reproduction technology (ART) outcomes: a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics 38(9): 2227-2235.
	Background: To investigate the thyroid function changes during controlled ovarian hyperstimulation (COH) and ascertain its impact on reproductive outcomes.; Methods: We conducted meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify studies reported changes in thyroid parameters during COH. We analyzed thyroid-stimulating hormone (TSH) levels, free thyroxin (fT4) levels, changes in estrogens (E2), thyroxine-binding globulin (TBG), relative risks (RRs) of clinical pregnancy rate (CPR), live birth rate (LBR), and mean difference (MD) of TSH increment between the miscarriage group and ongoing pregnancy group.; Results: This meta-analysis included fifteen individual studies (n = 1665 subjects). At the end of COH, the mean TSH (2.53 mIU/L; 95% CI, 2.19 to 2.88; I 2 = 92.9%) exceeded the upper limit (2.5 mIU/L) and remained above the threshold until one month following embryo transfer (ET). Thyroxin decreased from baseline to the end of COH (-0.18 ng/l; 95% CI, -0.35 to 0.00; I 2 = 92.2%). The CPR and LBR of patients with TSH exceeding the cutoff after COH were significantly lower than those of patients with TSH below the threshold (CPR: RR, 0.62; 95% CI, 0.47 to 0.82; I 2 = 0.0% and LBR: RR, 0.64; 95% CI, 0.44 to 0.92; I 2 = 0.0%). The MD of the increment in TSH levels between the miscarriage and ongoing pregnancy groups was 0.40 mIU/L (95% CI, 0.15 to 0.65; I 2 = 0.0%).; Conclusions: This meta-analysis shows that TSH increases and fT4 decreases during COH. COH-induced thyroid disorder impairs reproductive outcomes. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Li, F., et al. (2023). "HIFU as an alternative modality for patients with uterine fibroids who require fertility-sparing treatment." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 40(1): 2155077.
	Objectives: To compare pregnancy outcomes after high-intensity focused ultrasound ablation (HIFU), myomectomy and uterine artery embolization (UAE) for fertility-sparing patients with uterine fibroids and to investigate the possible mechanism of improving pregnancy by HIFU.; Materials and Methods: A meta-analysis of 54 studies containing 12,367 patients was conducted to compare the pregnancy outcomes of three fertility-sparing therapies. And a retrospective self-control study of 26 patients with uterine fibroids from May 2019 to December 2020 was performed to assess the blood flow impedance of bilateral uterine arteries before and after HIFU.; Results: In the analysis by treatment option, the pregnancy rate after myomectomy was 0.43 (95% CI 0.36-0.49), which was higher than 0.18 (95% CI 0.10-0.26) after HIFU, the latter was significantly higher than that after UAE (ratio 0.08, 95% CI 0.06-0.10). The miscarriage rate after HIFU was 0.08 (95% CI 0.04-0.12), which was similar to 0.15 (95% CI 0.09-0.21) after myomectomy and also similar to 0.16 after UAE (95% CI 0.01-0.30). In the subgroup analysis, women who received ultrasound guided HIFU (USgHIFU) were more likely to have ideal pregnancy outcomes than that after magnetic resonance imaging-guided HIFU. The pulsatility index and resistance index on the right side were significantly higher 3 months after HIFU than before (1.637 ± 0.435 vs. 1.845 ± 0.469; p = 0.033; 0.729 ± 0.141 vs. 0.784 ± 0.081, p = 0.039).; Conclusions: HIFU, especially USgHIFU, may be an alternative fertility-sparing modality for patients with uterine fibroids over 40 years old. HIFU may contribute to improving pregnancy rates by elevating uterine blood flow impedance.

Li, F., et al. (2023). "Effects of medical abortion assisted by traditional Chinese medicine: A network meta-analysis of randomized controlled trials." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.
	BACKGROUND: To what extent traditional Chinese medicine (TCM) combined with mifepristone and misoprostol is beneficial for improving the complete abortion rate and duration of vaginal bleeding has been a subject of debate in the field of medical abortion. OBJECTIVE: To assess the evidence regarding the complete abortion rate and duration of vaginal bleeding of medical abortion assisted by different kinds of TCM. SEARCH STRATEGY: We searched electronic databases such as PubMed, Web of Science and Cochrane Library database, China National Knowledge Internet, Wan fang Database, VIP Database, and China Biology Medicine disc from 2000 to February 15, 2023. SELECTION CRITERIA: The control group was medical abortion with mifepristone and misoprostol, and the experimental group was medical abortion assisted by TCM. DATA COLLECTION AND ANALYSIS: Major data extraction included sample size, age, medicine used for abortion, outcome measures. RevMan 5.3 and Stata 15.1 software were used to assess the literature quality and perform network meta-analysis, respectively. MAIN RESULTS: A total of 73 randomized controlled trials (RCTs) with 11 683 patients and nine kinds of TCM were included in this study. Compared with mifepristone and misoprostol, eight kinds of TCM had statistical significance in improving the complete abortion rate. The effect value of Sancao decoction was 5.86 (95% confidence interval [CI] 2.53-13.58). Seven kinds of TCM shortened the duration of vaginal bleeding. The effect value of comfrey and trichosanthin decoction was -8.75 (95% CI -10.86 to -6.64). CONCLUSIONS: This network meta-analysis showed that Lenge Zhumo decoction and Sancao decoction could have a large beneficial effect on complete abortion rate in medical abortion during early pregnancy, and comfrey and trichosanthin decoction could be the best TCM for shortening the duration of vaginal bleeding.

Li, F., et al. (2021). "The Efficacy of Vaginal Laser and Other Energy-based Treatments on Genital Symptoms in Postmenopausal Women: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(3): 668-683.
	Objective: This systematic review examined energy-based treatments of the vagina for postmenopausal vaginal symptoms.; Data Sources: We performed a systematic review from April 2017 (the end date of our previous review) to April 2020, searching Medline, Embase, and Scopus.; Methods of Study Selection: The inclusion criteria were all randomized studies, prospective studies with >10 cases, and retrospective studies with >20 cases published in English or French that assessed change in postmenopausal vaginal symptoms and/or sexual function in women after energy-based vaginal treatments. Meta-analyses were performed on randomized data.; Tabulation, Integration, and Results: Of the 989 results retrieved, 3 randomized studies, 16 prospective studies, and 7 retrospective studies were included in the review, representing data from 2678 participants. Pooled data from 3 randomized controlled trials show no difference between vaginal laser and topical hormonal treatments for change in vaginal symptoms (-0.14, 95% confidence interval -1.07 to 0.80) or sexual function scores (2.22, 95% confidence interval -0.56 to 5.00). Furthermore, no difference among vaginal laser, topical hormone, and lubricant was demonstrated in sexual function (p = .577). As in our previous review, non-randomized data support energy-based treatments in improving vaginal symptoms, sexual function, and clinician-reported outcomes. No severe adverse events were reported in the included studies. Significant heterogeneity of data arising from differing measures and reported outcomes continues to be an issue, with data remaining low quality, with high risk of bias, and no double-blind or placebo-controlled randomized trials yet reported, although 1 has now completed recruitment.; Conclusion: There are 3 randomized trials comparing energy-based systems with hormonal treatment, with no clinical difference in these 2 approaches. Although prospective data continue to show promising outcomes, without strong evidence from well-powered, double-blind placebo-controlled trials to determine the efficacy of treatment compared with placebo, the use of energy-based treatments should continue to be undertaken in research studies only, with high-quality studies essentially free from bias (International Prospective Register of Systematic Review registration number: 178346). (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Li, F., et al. (2022). "Four-Dimensional Image-Guided Adaptive Brachytherapy for Cervical Cancer: A Systematic Review and Meta-Regression Analysis." Frontiers in Oncology 12: 870570.
	Purpose: The ICRU/GEC-ESTRO released the ICRU Report No. 89, which introduced the concept of four-dimensional brachytherapy and ushered in a new era of brachytherapy for cervical cancer. The purpose of this study was to evaluate the local control and late toxicity of four-dimensional brachytherapy in cervical cancer through a systematic review and to reveal the dose-response relationship between the volumetric dose paraments and the local control rate via a probit model.; Material and Methods: We identified studies that reported the HR-CTV D90 and local control probabilities by searching the PubMed Database, the Web of Science Core Collection and the Cochrane Library Database through February 1st, 2022. Regression analyses were performed between the HR-CTV D90 and the local control probability using a probit model.; Results: Nineteen studies enrolling 3,616 patients were included. The probit model showed a significant relationship between the HR-CTV D90 value and IR-CTV D90 Vs. the local control probability, P < 0.001 and P = 0.003, respectively. The D90 for HR-CTV and IR-CTV corresponding to a probability of 90% local control was 79.1 GyEQD2,10 (95% CI:69.8 - 83.7 GyEQD2,10) and 66.5 GyEQD2,10 (95% CI: 62.8 - 67.9 GyEQD2,10), respectively. The limits for the prescribed dose of 85 GyEQD2,10 for HR-CTV D90 theoretically warranted a 92.1% (95% CI: 90.2% - 95.3%) local control rate, and 87.2% (95% CI: 82.4% - 91.8%) local control probability was expected for 65 GyEQD2,10 to IR-CTV D90. The probit model showed no significant relationship between the D2cc to organs at risk and the probability of grade 3 and above gastrointestinal or genitourinary toxicity.; Conclusions: Four-dimensional brachytherapy takes into account uncertain factors such as tumour regression, internal organ motion and organ filling, and provides a more accurate and more therapeutic ratio delivery through adaptive delineation and replanning, replacement of the applicator, and the addition of interstitial needles. The dose volume effect relationship of four-dimensional brachytherapy between the HR-CTV D90 and the local control rate provides an objective planning aim dose.; Competing Interests: Author MB was employed by Guowen Medical Corporation Changchun Hospital. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Li, Shi, Bu, Lu and Zhao.)

Li, F. G., et al. (2022). "Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial." Obstetrical and Gynecological Survey 77(7): 404-405.
	(Abstracted from JAMA 2021;326:1381–1389) An estimated 40% to 60% of women experience vaginal symptoms associated with menopause, which can lead to physical discomfort, as well as negatively affecting sexual function, relationships, and quality of life. Preliminary data have shown that fractional laser treatments used as nonhormonal alternatives for postmenopausal vaginal symptoms result in improvement in vaginal atrophy after treatment.

Li Fiona, G., et al. (2023). "Vaginal epithelial histology before and after fractional CO 2 laser in postmenopausal women: a double-blind, sham-controlled randomized trial." American Journal of Obstetrics and Gynecology 229(3): 278.e271-278.e279.
	Background: Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO 2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies.; Objective: This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies.; Study Design: This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY).; Results: There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166).; Conclusion: Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO 2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO 2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Li, G., et al. (2020). "Chinese herbal formula siwutang for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials." Maturitas 138: 26-35.
	Introduction: Primary dysmenorrhea (PD) is a common gynecological disorder that usually begins in adolescence, and affects patients' daily activities and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDS) are considered the first-line treatment, and hormonal contraceptives are also recommended for PD, but both are prone to side-effects. The Chinese herbal formula Siwutang (SWT) and its derivative formulas are a common treatment for PD in China. This review assessed the efficacy and safety of SWT for the treatment of PD.; Methods: PubMed, EmBase, Cochrane CENTRAL, CNKI, Wanfang and CBM were searched. We included randomized controlled trials (RCTs) that investigated SWT for PD, compared with no intervention, placebo, or conventional Western medicine. The outcome measurements included pain intensity measured by visual analogue scale (VAS) or other validated scales, the Cox Menstrual Symptom Scale (CMSS), quality of life, response rate and adverse events. The Cochrane Collaboration's tool was used to assess the risk of bias. RevMan V.5.3 was used for data synthesis and meta-analysis. Risk ratio (RR) with 95 % confidence intervals (CIs) or mean difference (MD) with 95 % CIs was calculated for dichotomous data or continuous data, respectively. Heterogeneity among studies was evaluated using both a chi-square test and an I 2 test.; Results: A total of 38 RCTs involving 3982 participants were identified. The methodological quality of the included trials was generally poor. Moreover, the results for SWT compared with placebo were unclear, as there was only 1 RCT. SWT improved pain intensity measured by VAS (3 RCTs, n = 220, MD:-2.61, 95 % CI:-3.72 to -1.51) when compared with conventional medicine, and these results were statistically significant. The meta-analysis showed the superior effect of SWT (including derivative formulas) on response rate (35 RCTs, n = 3,695, RR: 1.28, 95 % CI: 1.22-1.34) with medium heterogeneity (I 2 = 48 %). Both original SWT and its derivative formula XFSWT had a higher response rate than conventional medicine (23 RCTs, n = 2,493, RR: 1.28, 95 % CI: 1.23-1.33) (11 RCTs, n = 1,076, RR: 1.36, 95 % CI: 1.20-1.53). These results were statistically significant. No trial reported on quality of life or CMSS. Adverse events were reported by 5 studies, and meta-analysis showed SWT may be safer than conventional medicine in terms of the incidence of adverse events (3 RCTs, n = 236, RR: 0.17, 95 % CI: 0.07-0.38, I 2 = 0%).; Conclusion: In conclusion, the included trials showed favorable effects of SWT for treating primary dysmenorrhea when compared with conventional medicine. SWT may be safer than conventional medicine, but insufficient data was reported. The level of evidence is low because of the high risk of bias. Thus, further well-designed clinical trials with large sample sizes are warranted.; Registration Number: CRD42019136230 in PROSPERO 2019. (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Li, G., et al. (2022). "Which protocol is the best for patients with adenomyosis receiving in vitro fertilization/intracytoplasmic sperm injection: a meta-analysis."
	Review question The aim of the meta-analysis is to evaluate the advantages and disadvantages of ultralong, long, short and antagonist protocols in fresh ET cycles and the real effect of long acting GnRHa pretreatment in FET cycles. Besides these, we also try to clarify whether the fresh ET or FET is more optimal for patients with adenomyosis. Searches PubMed, Web of Science Types of study to be included Observational studies and randomized controlled trials Condition or domain being studied Adenomyosis is a benign gynecologic disease characterized by the presence of endometrial glands and stroma within the myometrium, surrounded by smooth muscle hyperplasia, which usually resulted in an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. The prevalence rate of adenomyosis was about 20% in infertile young women, and the proportion would increase up to 53% with coexistence of dysmenorrhea or hypermenorrhea. Adenomyosis is a continuing problem for unsatisfied pregnancy outcomes. Previous studies mainly focusing on the poor reproductive, obstetric or perinatal outcomes in adenomyotic population compared with non-adenomyotic population. In terms of detailed protocols, no systematic comparison was carried out, similarly, no recommendation about the fresh ET or FET should be adopted. Participants/population Patients with or without adenomyosis diagnosed by TVS or MRI. Intervention(s), exposure(s) Patients with adenomyosis receiving ultralong, long, short or antagonist protocols in Fresh ET cycles of IVF/ICSI cycles Patients with adenomyosis receiving long acting GnRHa pretreatment in FET cycles or not Comparator(s)/control Patients without adenomyosis in IVF/ICSI cycles Main outcome(s) The primary outcomes is live birth rate Additional outcome(s) The second outcomes are clinical pregnancy rate and miscarriage rate. Measures of effect The odds ratio (OR) and 95% confidence interval (CI) were adopted. Data extraction (selection and coding) Data were extracted from all eligible studies by two independent reviewers(LiGe and Wenting Wang). The basic characteristics and outcome variables were as follows: author&year of publication, country, study design, age, case group, control group, number of cycles, protocols of embryo transfer, mode of conception, number of IVF/ICSI cycles, methods of diagnosis and outcome variables. Risk of bias (quality) assessment Newcastle-Ottawa Scale is used for the bias assessment of the included studies. Strategy for data synthesis All meta-analysis were performed by Revman 5. The odds ratio (OR) and 95% confidence interval (CI) were adopted to evaluate pregnancy outcomes of different protocols in IVF/ICSI cycles. Heterogeneity was measured by Q-test and I² scores. The random effects model was applied when I² ＞ 50%, otherwise the fixed effects model was used. If obvious heterogeneity existed, sensitivity analysis was conducted. P<0.05 was considered as statistical significance. Analysis of subgroups or subsets ultralong protocol in adenomyotic population VS no restricted protocols in non-adenomyotic population in fresh ET cycles long, short or antagonist protocols in adenomyotic population VS no restricted protocols in non-adenomyotic population in fresh ET cycles long acting GnRHa pretreatment in adenomyotic population VS no GnRHa pretreatment in non-adenomyotic population in FET cycles no long acting GnRHa pretreatment in adenomyotic population VS no GnRHa pretreatment in non-adenomyotic population in FET cycles ultralong protocol in adenomyotic population in fresh cycles VS long acting GnRHa pretreatment in FET cycles in adenomyotic population Contact details for further information Li Ge geli1128@163.com Organisational affiliation of the review The Second Hospital, Cheeloo College of Medicine, Shandong University Review team members and their organisational affiliations Dr Li Ge. The Second Hospital, Cheeloo College of Medicine, Shandong University Dr Wenting Wang. The Second Hospital, Cheeloo College of Medicine, Shandong University Yexing Li. The Second Hospital, Cheeloo College of Medicine, Shandong University Dr Zhongyuan Li. The Second Hospital，Cheeloo College of Medicine，Shandong University Dr Linlin Cui. The Second Hospital，Cheeloo College of Medicine，Shandong University Type and method of review Systematic review Anticipated or actual start date 01 April 2022 Anticipated completion date 31 July 2022 Funding sources/sponsors The study is funded by Natural Science Foundation of Shandong Province(ZR2021MH390). Grant number(s) State the funder, grant or award number and the date of award Li Ge, ZR2021MH390. Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Adenomyosis; Female; Fertilization in Vitro; Humans; Male; Meta-Analysis as Topic; Sperm Injections, Intracytoplasmic; Spermatozoa Date of registration in PROSPERO 01 July 2022 Date of first submission 21 June 2022 Stage of review at time of this submission

Li, H. and L. J. Liao (2023). "Efficacy of hyperthermic intraperitoneal chemotherapy plus cytoreductive surgery for advanced or recurrent ovarian cancer: a systematic evaluation and meta-analysis." European Review for Medical and Pharmacological Sciences 27(17): 8135-8143.
	Objective: This meta-analysis was performed to investigate the safety and efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) in the treatment of advanced or recurrent ovarian cancer.; Materials and Methods: An electronic search of databases, including PubMed, Embase, Cochrane, Medline, and Web of Science, was performed to collect controlled studies on HIPEC combined with CRS administered for advanced ovarian cancer. Meta-analysis was conducted based on the outcome indicators extracted from the included studies, including disease-free survival (DFS), overall survival (OS), and adverse events (AEs).; Results: Twelve pieces of literature were included, involving 1,622 participants, with 694 participants in the control group and 928 in the study group. In terms of DFS, the pooled hazard ratio (HR) was 0.70 (95% CI: 0.58, 0.84), with an HR of 0.77 (95% CI: 0.64, 0.93) in the treatment-naïve subgroup and an HR of 0.54 (95% CI: 0.40, 0.74) in the secondary cytoreduction subgroup. In terms of OS, the pooled HR was 0.63 (95% CI: 0.52, 0.77), with an HR of 0.67 (95% CI: 0.54, 0.83) in the treatment-naïve subgroup and an HR of 0.47 (95% CI: 0.29, 0.77) in the secondary cytoreduction subgroup. With regard to AEs, the pooled odds ratio (OR) was 0.79 (95% CI: 0.68, 0.92).; Conclusions: The benefits of CRS plus HIPEC for the management of advanced ovarian cancer are significant but also associated with an increased risk of adverse events. Thus, clinical use of this co-administration requires caution.

Li Heidi, O.-Y., et al. (2022). "Lasers as an adjuvant for vulvar lichen sclerosus: A systematic review and meta-analysis." Journal of the American Academy of Dermatology 86(3): 694-696.
	To the Editor: Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis that can result in significant psychosocial and sexual impairment. VLS is associated with 4%-6% risk of malignant transformation if left untreated.1 The effective management of VLS can be challenging as some patients can be recalcitrant to first-line ultrapotent topical corticosteroids (TCS) despite appropriate use.2 Off-label use of lasers has shown good results in VLS, suggesting its usefulness as an adjunct to medical therapy. This combined systematic review and meta-analysis synthesizes the available evidence for ablative and nonablative lasers for VLS. PRISMA guidelines were followed (PROSPERO protocol: CRD42020209207). MEDLINE, EMBASE, and CENTRAL databases were searched from inception to September 15, 2020. Controlled studies were assessed using the Cochrane risk of bias tool 2.0 and were meta-analyzed via Review Manager using standardized mean difference in accordance with published guidelines.3 Of 234 unique records, 13 studies comprising 307 patients with VLS were included (Fig 1, Supplemental Table SI available via Mendeley at https://doi.org/10.17632/mykgjhccm3.1). Of these 13 studies, 11 studies were nonrandomized and 2 were randomized. Of these, 9 studies used fractionated ablative lasers, 2 used nonfractionated ablative lasers, and 2 used nonablative lasers. Long-term malignancy risk or recurrence was not investigated in any of the included studies. Follow-ups ranged from 1 month to 4 years.

Li, H. F., et al. (2020). "Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis." Evidence-based Complementary and Alternative Medicine 2020: 1789304.
	Context. Premature ovarian insufficiency (POI) is one of the difficult gynecological diseases with complex etiologies. Tonifying kidney (bushen) and activating blood (huoxue) prescription (TKABP) is a popular traditional Chinese medicine (TCM) therapy which is commonly applied for POI. However, its efficacy and safety are still controversial. Objective. We carried out this systematic review and meta-analysis to evaluate the effectiveness of TKABP on POI. Methods. The following eight databases were searched from the establishment to September 30, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results. Twenty-three RCTs involving 1712 patients with POI were included. Compared to hormone therapy (HT) groups, TKABP groups showed a significantly higher total effective rate (RR: 1.10; 95% CI: 1.04-1.17; P<0.01, I2 = 32%). In addition, TKABP groups revealed a better improvement in terms of serum follicle-stimulating hormone (FSH) levels, serum estradiol (E2) levels, peak systolic velocity (PSV) of ovarian stromal blood, and Kupperman index (KI) score. However, serum luteinizing hormone (LH) levels and ovarian volume (OV) showed no significant statistical difference. Subgroup analyses showed that herbal paste and 3 months of treatment duration had a greater effect on the improvement of hormone levels. Besides, the occurrence of related adverse events in TKABP groups was lower than that in HT groups. Conclusions. Our review suggests that TKABP appears to be an effective and safe measure for patients with POI, and the herbal paste may be superior. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with furthermore standardized researches of rigorous design.Copyright © 2020 Hui-Fang Li et al.

Li, H.-F., et al. (2022). "The efficacy of Shenghua Decoction supplementation after early medical abortion: A meta-analysis of randomized controlled trials." Complementary Therapies in Medicine 69: 102848.
	Aims: Shenghua Decoction (SHD) is a well-known classic herbal formula documented in traditional Chinese medicine (TCM) that has been widely applied during the postpartum period in Chinese communities for several years. We conducted this systematic review and meta-analysis to explore the influence of SHD as an adjuvant treatment for early medical abortion using a combination of mifepristone followed by misoprostol.; Methods: This systematic review and meta-analysis was reported using 2020 PRISMA guidelines. Eight databases were searched from their establishment to February 28, 2022, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, the Chinese BioMedical database, the Chinese Scientific Journal Database, and the Wanfang database. The Grading of Recommendations Assessment, Development, and Evaluation estimated the quality of evidence.; Results: Sixteen RCTs involving 3016 patients were included in the meta-analysis. Overall, compared with no treatment as the control group after early medical abortion, patients treated with SHD were associated with a higher complete abortion rate (RR: 1.14; 95% CI: 1.10 - 1.18; P < 0.01, I 2 = 26%, moderate quality), lower incomplete abortion rate (RR: 0.31; 95% CI: 0.24 - 0.41; P < 0.01, I 2 = 0%, moderate quality), and lower viable pregnancy rate (RR: 0.26; 95% CI: 0.11 - 0.62; P < 0.01, I 2 = 0%, moderate quality). Additionally, SHD supplementation was associated with reduced the induction-abortion time, duration of vaginal bleeding and menstrual recovery time.; Conclusion: Our findings suggest that SHD supplementation may be beneficial for women seeking a medical abortion before the 7-week gestational period and no adverse events in the experimental group were reported. However, the methodological quality of the included RCTs was unsatisfactory, and therefore it is necessary to further verify the effectiveness of SHD using standardized studies of rigorous design. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Li, H.-F., et al. (2020). "The Efficacy of Traditional Chinese Medicine Shoutai Pill Combined with Western Medicine in the First Trimester of Pregnancy in Women with Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta-Analysis." BioMed Research International 2020: 7495161.
	Background: Shoutai Pill (STP), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating unexplained recurrent spontaneous abortion (URSA). This systematic review and meta-analysis aims at evaluating the efficacy and safety of STP in the first trimester of pregnancy in women with a history of unexplained recurrent spontaneous abortion.; Methods: The following eight databases were searched from their establishment to Dec 31, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).; Results: A total of 12 studies (916 patients) with URSA were contained in this meta-analysis. The forest plot showed that patients treated with Shoutai Pill and western medicine had a significantly lower incidence of early pregnancy loss (RR: 0.42; 95% CI: 0.34-0.52; P < 0.01, I 2 = 0%). Subgroup analysis revealed that different types of TCM syndrome differentiation had the similar results. Also, in the combined group, patients had a lower TCM syndromes and symptoms and serum D-dimer level, while higher incidence of live birth.; Conclusions: Our findings suggest that cotreatment with STP and western medicine might be superior to western medicine alone in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent spontaneous abortion, and there was no adverse event in the experimental group reported. However, the methodological quality of included RCTs was unsatisfactory; it is necessary to verify its effectiveness with further more standardized researches of rigorous design.; Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper. (Copyright © 2020 Hui-fang Li et al.)

Li, J. (2019). "Diarrhea With HER2-Targeted Agents in Cancer Patients: A Systematic Review and Meta-Analysis." Journal of Clinical Pharmacology 59(7): 935-946.
	To fully investigate the diarrhea of human epidermal growth factor receptor 2 (HER2)-targeted agents in cancer patients. The relevant studies of the randomized, controlled trials (RCTs) in cancer patients treated with HER2-targeted agents were retrieved, and the systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until August 2018. Forty-two RCTs and 21 633 patients were included. The current meta-analysis suggested that the use of HER2-targeted agents significantly increases the risk of developing all-grade diarrhea (RR, 2.78; 95%CI, 2.37-3.25; P <.00001) and high-grade diarrhea (RR, 4.89; 95%CI, 3.09-7.75; P <.00001). The RRs of all-grade diarrhea and high-grade diarrhea varied significantly according to drug type, control group, and treatment regimen. The RR of all-grade diarrhea varied significantly according to tumor type. Afatinib and neratinib tended to associate with the highest risk of all-grade diarrhea and high-grade diarrhea, respectively. Trastuzumab was associated with the lowest risk of diarrhea. Breast cancer patients tended to have a higher risk of all-grade diarrhea than patients with nonbreast cancer when receiving a HER2-targeted agent. The available data suggested that the use of HER2-targeted agents is associated with a significantly increased risk of diarrhea in cancer patients.Copyright © 2019, The American College of Clinical Pharmacology

Li, J., et al. (2021). "Doppler Imaging Assessment of Changes of Blood Flow in Adenomyosis After Higher-Dose Oxytocin: a Randomized Controlled Trial." Journal of ultrasound in medicine.
	OBJECTIVES: to assess the changes of blood flow in adenomyosis (AM) after higher‐dose oxytocin (OT) in different doses, and to evaluate the safety for patients. METHODS: a total of 124 patients with AM were randomly divided into 4 groups with continuous intravenous infusion of OT as 0.06, 0.12, 0.24 and 0.36 U/min, respectively. The changes of arteries of AM before and after intravenous infusion of OT were observed by color Doppler ultrasound. The changes of blood flow volume of the artery of AM before and after intravenous infusion of OT were compared among the 4 groups, and the vital signs and adverse drug reactions were monitored during intravenous drip. RESULTS: during the trial, no severe adverse reactions occurred and the vital signs of all the patients were stable. Among the 4 groups, it was found that there was a significant difference in the change of blood flow volume of blood artery in AM lesions between 0.06 U/min OT group and the other three groups after intravenous drip of OT (P < .05), but there was no significant difference in blood flow volume among the three groups (P > .05), and the difference of adverse drug reactions was statistically significant with the increase of OT dose (P < .05). CONCLUSION: OT can effectively reduce the blood flow volume of AM lesions, and continuous intravenous infusion of 0.12 U/min OT is an appropriate dose that can not only minimize the blood flow volume but also reduce the incidence of adverse drug reactions.

Li, J., et al. (2021). "Dilatation and curettage versus lesion resection in the treatment of cesarean-scar-pregnancy: A systematic review and meta-analysis." Taiwanese Journal of Obstetrics and Gynecology 60(3): 412-421.
	This meta-analysis was performed to compare the efficacy and safety of dilatation and curettage (D&C) (simply D&C or combined with other treatments) and lesion resection for cesarean scar pregnancy (CSP). A search of English and Chinese databases from 2010 to 2019 was conducted. Thirty one studies were retrieved including sixteen random controlled and fifteen case controlled trials. Compared with abdominal resection surgery(ARS) and vaginal resection surgery(VRS), uterine artery embolization(UAE)+D&C has no obvious difference in curative effect and safety (UAE + D&C versus ARS: Cure rate(CR): P = 0.076, time for menstruation recovery/beta-HCG normalization: P = 0.545/0.949,Blood loss: P = 0.005, adverse event: P = 0.420; versus VRS: CR: P = 0.085, time for menstruation recovery/beta-HCG normalization: P < 0.001/P = 0.031,Blood loss: P = 0.902, adverse event: P = 0.249). UAE + D&C associated with lower blood loss and less postoperative complication than laparoscopic resection surgery(LRS), but LRS take more advantages in terms of the curative effect (CR: P = 0.047, time for menstruation recovery/beta-HCG normalization: P = 0.352/0.103). The efficacy and safety of VRS are better than D&C, methotrexate (MTX) + D&C (D&C versus VRS: CR: P < 0.001, time for beta-HCG normalization: P = 0.363,blood loss: P < 0.001, adverse event: P = 0.046; MTX + D&C versus VRS: CR: P < 0.001, time for menstruation recovery/beta-HCG normalization: P < 0.001/P = 0.005, blood loss: P < 0.001, adverse event: P < 0.001). Lesion resection had advantages in shorter time for menstrual recovery/beta-HCG normalization and less adverse events, lower failure rate over the administration of D&C treatments. In detail, the curative effect of UAE + D&C is similar to ARS and VRS, but inferior to LRS, while the safety of UAE + D&C is better than LRS. The efficacy and safety of simply D&C and MTX + D&C are not as good as VRS.Copyright © 2021

Li, J., et al. (2021). "Efficacy and safety of phytoestrogens in the treatment of perimenopausal and postmenopausal depressive disorders: A systematic review and meta-analysis." International Journal of Clinical Practice 75(10): e14360.
	Background: Depression is one of the most common and specific symptoms among menopausal women, leading to significant personal, family, and economic burdens. Some studies have shown that phytoestrogens can help relieve symptoms of depression.; Objectives: This systematic review and meta-analysis aim to assess the efficacy and safety of phytoestrogens in treating depression among menopausal women.; Methods: A comprehensive search for relevant studies published until November 25, 2020, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science, and EMBASE. Statistical analyses were performed with R 4.0.3.and Review Manager 5.4.; Results: 2183 studies were identified and 10 studies with 15 independent reports were included, involving 1248 participants. The quality of the four studies was assessed as high risk, six studies were assessed as unclear. The analyses conducted according random effects model indicated the significant positive effect on depressive symptoms for postmenopausal women compared with the placebo (SMD = -0.62; 95% CI = -1.13 to -0.12; Q = 45.62, df = 14, P < .01; I 2 = 79%). The low dose phytoestrogens (25 mg/d ≤ dose ≤ 100 mg/d) have better effectiveness (SMD = -0.52; 95% CI = -0.85 to -0.20; I 2 = 79%, P< .01) than high dose (dose > 100 mg/d) and ultralow dose (0 < dose < 25 mg/d), but showed no statistical significance (Q = 0.81 df = 2, P = .67). Isoflavones had better effectiveness (SMD = -0.48; 95% CI = -0.75 to 0.21; I 2 = 75%, P < .01) than lignans of phytoestrogens (SMD = -0.22; 95% CI = -0.37 to 0.08; I 2 = 0%, P = .96). The duration of intervention affects the efficacy of phytoestrogens (β = -0.03; 95% CI: [-0.05, 0.00]; P = .045). The effectiveness varies in regions. The adverse reactions frequently reported were gastrointestinal symptoms and cold or upper respiratory tract infection.; Conclusions: Phytoestrogen can relieve depression symptoms among menopausal, especially for postmenopausal women who take low doses(25 mg/d ≤ dose ≤ 100 mg/d) of phytoestrogens for a long-term duration. Although mild adverse reactions have been reported, phytoestrogen could be considered as a complementary treatment for postmenopausal depression. (© 2021 John Wiley & Sons Ltd.)

Li, J., et al. (2021). "Effect of telehealth interventions on quality of life in cancer survivors: A systematic review and meta-analysis of randomized controlled trials." International journal of nursing studies 122.
	Background: With advances in cancer disease diagnosis and treatment, the trends of cancer survival continue to increase, but cancer survivors usually experience disease- or treatment-related problems (including both physiological and psychological problems) and poorer quality of life. Various types of telehealth interventions have been widespread in the field of medical care and have been shown to be cost-effective, to have high levels of patient satisfaction, and to have high acceptability among health professionals. Currently, there is no definite conclusion about the effectiveness of telehealth interventions on cancer survivors' quality of life. Objectives: To evaluate the effects of telehealth interventions on cancer survivors' quality of life and compare the effectiveness of different types. Design: A systematic review and meta-analysis. Methods: A systematic literature search was conducted in six databases (MEDLINE, Embase, the Cochrane Central Register of Controlled trials, CINAHL, PsycINFO, and Web of Science) to identify relevant studies from inception to 14 April 2021. Two reviewers independently screened studies and extracted the data. The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. Data synthesis was conducted in Review Manager (Version 5.3), and the quality of life scores were calculated by using the standard mean difference (SMD) and 95% confidence intervals (CIs). Sensitivity analysis and subgroup analysis were also conducted. Results: Twenty-eight randomized controlled trials (RCTs) published from 2002 to 2020 were included. Meta-analysis revealed significant effects of telehealth interventions on cancer survivors' quality of life (SMD = 0.24, 95% CI: 0.14-0.34, P < 0.00001). Subgroup analysis showed that the most effective method was application-based intervention (SMD = 0.41, 95% CI: 0.17-0.66) and the short-term telehealth intervention was more effective than other durations of intervention (SMD = 0.28, 95% CI: 0.06-0.50). The effects on breast cancer survivors' quality of life were greater than those on the other types of cancer survivors (SMD = 0.30, 95% CI: 0.10-0.51). Sensitivity analysis indicated that the pooled results were robust and reliable. Conclusion: Telehealth interventions are effective and alternative methods for improving quality of life among cancer survivors. The most effective approach was application-based intervention, the most common approach was website-based intervention, and in terms of intervention durations, the short-term telehealth intervention was the most effective. Most telehealth interventions included breast cancer survivors. More large, well-designed RCTs are needed to confirm the effects of telehealth interventions on quality of life in cancer survivors. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Li, J., et al. High-intensity focused ultrasound ablation versus surgical resection for treating abdominal wall endometriosis: a systematic review and meta-analysis.
	Background Abdominal wall endometriosis (AWE) is the most common type of extrapelvic endometriosis in women of reproductive age, and several studies have compared high-intensity focused ultrasound (HIFU) ablation with surgical resection in the managem

Li, J., et al. (2020). "The Effect of Male Sexual Abstinence Periods on the Clinical Outcomes of Fresh Embryo Transfer Cycles Following Assisted Reproductive Technology: A Meta-Analysis." American journal of men's health 14(4): 1557988320933758.
	A sexual abstinence period (SAP) lasting for 2-7 days is recommended before undertaking semen analyses. However, there is no consensus regarding the length of the SAP for couples using assisted reproductive technology (ART). Therefore, a meta-analysis was performed to compare the effect of short SAPs (less than 4 days) and long SAPs (4-7 days) on the clinical outcomes of fresh embryo transfer cycles after ART. A total of four studies were included in the meta-analysis. Although the fertilization rate in short SAP couples was higher than that in long SAP couples, a pooled analysis demonstrated that it was not statistically significant ( p = .09). The implantation rate was, however, significantly higher in short SAP couples ( p = .0001). The pooled analysis revealed that the pregnancy rate was significantly higher in short SAP couples than that in long SAP couples. The overall odds ratio (OR) for the pregnancy rate was 1.44 ( p = .0006). No significant difference in miscarriage rates between the short and long SAP couples was found ( p = .88). The meta-analysis indicates that a shorter abstinence period could result in higher implantation and pregnancy rates for patients undertaking ART treatments.

Li, J., et al. (2022). "Effect of different intervention methods on postoperative local recurrence of endometrial cancer: A systematic review and meta-analysis." Asian journal of surgery 45(11): 2372-2374.
	To the editor, Endometrial cancer (EC) is one of the malignant tumors of the female genital tract, ranking second in malignant tumors of the female reproductive system in China.1 Staged surgery is the standard treatment for EC, and staged surgery can comprehensively and accurately reflect the metastasis and invasion of EC, including extrafascial hysterectomy and salpingo-oophorectomy.2 Although early EC can be easily detected, the recurrence rate is still high after standard surgery. Among them, postoperative recurrence includes systemic recurrence and local recurrence.3 It is known that age and infiltration affect the recurrence of EC, but the influencing factors of postoperative recurrence have not been systematically analyzed. Therefore, this study aimed to identify the risk factors for postoperative local recurrence of EC by meta-analysis. Systematic reviews and meta-analyses were conducted according to PRISMA guidelines. Relevant articles were obtained from PubMed, Medline, Embase, and Cochrane. A total of 15 high-quality studies were included, including 5825 patients. There were 2984 cases in the experimental group and 2841 cases in the control group (Table 1). A total of 153 patients (5.1%) in the experimental group and 273 patients (9.6%) in the control group developed local recurrence in the 15 studies. Finally, 7 studies showed that the local recurrence rate of patients with different surgical methods or adjuvant therapy was significantly lower than that of patients in the control group, and the difference had statistical significance (P < 0.05). Our results showed that in patients with EC whose lesions involved the uterus but were confined to the uterus, surgery combined with external pelvic irradiation had a lower postoperative local recurrence rate than surgery alone (Fig. 1C). For high-risk groups, surgery combined with chemoradiotherapy can also reduce local recurrence in EC patients with recurrent factors (Fig. 1B). However, there were no significant differences between laparoscopic and open surgery and between different radiotherapy locations (Fig. 1A, D). We further used R language to generate an EC-related prediction model based on collated data, in which clinical-stage, age, and histologic grade were all critical factors in the prediction model. In predicting survival rates at 3, 5, and 10 years, it can be seen that survival rates become lower with an increasing number of years (Supplementary figure 1). Table 1. Basic information of the 15 included studies. Study	Experiment Group (n)	Intervention Method	Recurrence (n)	Control (n)	Recurrence (n)

Li, J., et al. (2021). "Effects of oral contraceptive for different responder women before GnRH antagonists: a systematic review and meta-analysis." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(11): 977-986.
	This analysis aimed to compare the efficacy of oral contraceptive pill (OCP) pretreatment for gonadotropin-releasing hormone antagonist (GnRH-ant) protocol, especially for different responder women. The PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for trials on with and without OCP pretreatment before stimulation with gonadotropins. The standardized mean differences (SMDs) or pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used for statistical analysis. Fifteen studies with 5326 in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were summarized. The clinical pregnancy rate, moderate or severe ovarian hyper-stimulation syndrome (OHSS) rate, and miscarriage rate was not found to be significantly different between patients with and those without OCP pretreatment, even after sensitivity analyses. In addition, there were still no statistically significant differences for the subgroups analyses of hyper-responders, poor responders, and normal responders. No significant differences were detected in the duration of ovarian stimulation, gonadotropin dose consumed, endometrial thickness on day of oocyte collection, or number of oocytes. This meta-analysis did not find an unequivocally beneficial effect of OCP pretreatment for different responder women with using a GnRH-ant protocol. The clinician should weigh the advantages and disadvantages of OCP pretreatment and guide the treatment scheduling considering the patient's own situation.

Li, J., et al. (2022). "Impact of Chinese Herbal Medicine on Glucolipid Metabolic Outcomes in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2022: 3245663.
	Objective: This investigation was conducted to analyze and evaluate the impact of Chinese herbal medicine on glucolipid metabolism in women with polycystic ovary syndrome (PCOS).; Methods: We used manual and computer-aided search methods, and the search scopes included Chinese databases (China National Knowledge Infrastructure, Wanfang, the China Science and Technology Journal Database, and the Chinese Biomedical Literature Database) and English databases (PubMed, Embase, Web of Science, and the Cochrane Library). We searched these eight databases for randomized controlled trials investigating the effects of Chinese herbal medicine on glucolipid metabolism in women with PCOS, with the retrieval deadline being June 2021. Two reviewers screened, selected, and extracted data and verified the results independently. The NoteExpress software was used to manage and screen the literature, the risk of bias assessment tool was used to evaluate the methodological quality of the included studies, and the RevMan 5.4 software was used for meta-analysis.; Results: A total of 13 trials were included, including 825 patients with PCOS. Because the drugs used in the control group were different, we divided the results into two parts, with four trials using placebo and nine trials using metformin as the control. The results of the meta-analysis showed that fasting insulin (MD = -2.45, 95% CI = [-4.74, -0.17], P = 0.04), 2 h fasting plasma glucose (MD = -0.33, 95% CI = [-0.64, -0.02], P = 0.04), serum total cholesterol (MD = -0.38, 95% CI = [-0.58, -0.18], P = 0.0002), triglycerides (MD = -0.36, 95% CI = [-0.58, -0.14], P = 0.001), and low-density lipoprotein cholesterol (MD = -0.58, 95% CI = [-0.75, -0.41], P < 0.00001) were significantly improved in the Chinese herbal medicine group compared with the placebo group. In addition, compared with metformin, body mass index (MD = -1.04, 95% CI = [-1.55, -0.53], P < 0.0001), serum total cholesterol (MD = -0.27, 95% CI = [-0.46, -0.07] P = 0.007), and low-density lipoprotein cholesterol were significantly reduced (MD = -0.12, 95% CI = [-0.22, -0.02], P = 0.02) and high-density lipoprotein cholesterol (MD = 0.09, 95% CI = [0.02, 0.17], P = 0.01) was significantly improved after treatment with Chinese herbal medicine.; Conclusion: Compared with the placebo group, Chinese herbal medicine had positive effects on glucolipid metabolism in women with PCOS. Chinese herbal medicine had a positive effect on lipid metabolism when the control group was metformin, but no effect on glucose metabolism. These findings need to be verified in high-quality, large-sample, randomized controlled trials in the future.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Jie Li et al.)

Li, K. P., et al. (2021). "Surgical Outcomes of Transperitoneal Para-Aortic Lymphadenectomy Compared With Extraperitoneal Approach in Gynecologic Cancers: A Systematic Review and Meta-Analysis." Frontiers in surgery 8: 779372.
	Purpose: The optimal surgical approach for para-aortic lymphadenectomy (PALND) in gynecologic cancers using minimally invasive surgery (laparoscopy or robotic-assisted) is controversial. This study summarizes the current evidence on the extraperitoneal (EP) approach and compares its perioperative, surgical outcomes, and complications to the transperitoneal (TP) approach in an updated meta-analysis. Methods: We performed a systematic search in PubMed, Embase, Web of Science, Cochrane Library database for randomized controlled trials (RCTs) and non-RCTs that compare EP to TP for PALND. The main outcomes included surgical, perioperative outcomes, and complications. The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables with 95% CIs. Three RCTs and 10 non-RCTs trials, including 2,354 patients were identified and enrolled in the meta-analysis. Results: A total of three RCTs and ten non-RCTs trials, including 2,354 patients were identified and enrolled in the meta-analysis. We reported similar results for EP and TP in terms of the hospital stay, estimated blood loss, blood transfusion, conversion to laparotomy, total operative time, and postoperative complications (Clavien grade ≥ 1 and Clavien grade ≥ 3). However, the PALND operative time (WMD -10.46 min, 95% CI -19.04, -1.88; p = 0.02) and intraoperative complications (OR 0.40, 95% CI 0.23, 0.69; p = 0.001) were less with EP. Also, more nodes were removed in EP compared with the TP (WMD 1.45, 95% CI 0.05, 2.86; p = 0.04). Conclusions: The EP approach did not show differences regarding surgical and perioperative parameters compared with the TP approach. However, the number of aortic nodes retrieved was higher. Furthermore, The PALND operative time and intraoperative complications were less in EP.

Li, L., et al. (2021). "Meta-Analysis of the Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Patients With Polycystic Ovary Syndrome." American journal of therapeutics 29(2): e245-e248.
	Competing Interests: The authors have no conflicts of interest to declare.

Li, L.-N., et al. (2023). "The effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion: a systematic review and meta-analysis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 36(1): 2209818.
	Background: Transcervical resection of adhesion (TCRA) and postoperative adjuvant estrogen and progestin are the main treatments for cavity adhesions, but the recurrence rate after surgery is still high. It was showed that aspirin could promote endometrial proliferation and repair after TCRA in patients with severe cavity adhesions, but the effect on reproduction was uncertain.; Objective: To assess the effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion.; Methods: The databases used included Cumulative Index to PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang database. Studies published before June 2022 were included. Each participant received an aspirin-based intervention aimed at improving uterine status, which was compared to a sham intervention. The primary outcome measure was a change in endometrium thickness. Secondary outcomes included uterine artery resistance index, blood flow index, and endometrial arterial resistance index.; Result: A total of 19 studies ( n = 1361 participants) that met the inclusion criteria were included in this study. The aspirin-based intervention was strongly associated with better clinical outcome at second-look endometrium thickness (MD 0.81, CI 0.46-1.16; p < .00001) and blood flow Index (FI) (MD 4.1, CI 2.3-5.9; p < .00001). Besides, the analysis of arterial pulsatility index (PI) showed a significantly reduced after transcervical resection of adhesion (MD -0.9, CI -1.2 to 0.6; p < .00001); whereas no significant difference was found in endometrial arterial resistance index (RI) (95% CI, -0.30 to 0.01; p = .07).; Conclusion: Our study proved the effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion. However, the review requires evidence from additional randomized controlled trials and high-quality research. More strictly designed research studies are needed to assess the effectiveness of aspirin administration after transcervical resection of adhesion.

Li, M., et al. (2019). "Adjuvant chemoradiotherapy versus radiotherapy in cervical cancer patients with intermediate-risk factors: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 238: 1-6.
	Background: At present, extensive hysterectomy and pelvic lymph node dissection are preferred for early-stage cervical cancer. However, additional adjuvant therapy could be considered if there is a risk for recurrence. Postoperative pelvic radiotherapy plus concurrent platinum-based chemotherapy are recommended for patients with high risk factors. The treatment regimen for patients with intermediate-risk factors, however, remains unclear. We, thus, performed a systematic review and meta-analysis to assess the recurrence-free survival (RFS), overall survival (OS), grade III/IV hematologic toxicity and grade III/IV non-hematologic toxicity in chemoradiotherapy (CRT) versus radiotherapy (RT) groups.; Methods: We systematically searched PubMed, Cochrane, and Embase to identify relevant studies published before November 30, 2018 to compare CRT with RT as a postoperative adjuvant therapy in early-stage cervical cancer patients with intermediate-risk factors. We used Stata (version 14.0) to calculate odds risks (ORs) and 95% confidence intervals (CIs) and pooled data was assessed by the fixed-effects model.; Results: Of the 428 identified studies, only 9 were eligible and included in our analysis (CRT: n = 870; RT: n = 932). CRT significantly prolonged RFS (OR = 3.43, 95% CI 2.08-5.67, P = 0.000) and OS (OR = 1.80, 95% CI 1.30-2.50, P = 0.000). The occurrence rate of grade III/IV hematologic toxicity (OR = 16.07, 95% CI 6.47-39.93, P = 0.000) was significantly higher in CRT, while grade III/IV non-hematologic toxicity was ambiguous for CRT and RT with an OR of 1.91 (95% CI 0.95-3.83, P = 0.069).; Conclusions: For early-stage cervical cancer patients with intermediate-risk factors, CRT can dramatically improve RFS and OS compared with RT. Apart from the increase in grade III/IV hematologic toxicity, CRT was well tolerated and accepted treatment for early-stage cervical cancer. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Li, M., et al. (2019). "Chinese herbal formulae for the treatment of menopausal hot flushes: A systematic review and meta-analysis." PloS One 14(9): e0222383.
	Objectives: This systematic review aimed to evaluate the therapeutic effects and safety of Chinese herbal medicine (CHM) formulae for managing menopausal hot flushes (MHF).; Methods: Seven English and Chinese databases were searched for studies from respective inceptions to February 2019. Randomized controlled trials investigating the clinical effects and safety of CHM formulae on MHF were considered for inclusion. The outcomes of subjective feelings (MHF and quality of life), objective changes (hormones and peripheral blood flow) and safety were analyzed. The most frequently prescribed formulae and herbs were summarized.; Results: Nineteen randomized clinical trials involving 2469 patients were included. When compared to menopausal hormone therapy, CHM had similar effects to menopausal hormone therapy on total effectiveness rate (OR 1.41, 95% CI 0.84 to 2.35) and total Kupperman index (KI) score (SMD -0.13, 95% CI -0.61 to 0.36), and could significantly reduce vasomotor symptom score (MD -0.43, 95% CI -0.55 to -0.31) and upper-body peripheral blood flow (MD -3.56, 95% CI -5.14 to -1.98 under the jaw, MD -7.10, 95% CI -11.01 to -3.19 in the fingertip). When compared to placebo, CHM could reduce MHF severity (MD -0.70, 95% CI-1.00 to -0.40) and improve total KI score (MD -12.61, 95% CI -15.21 to -10.01). However, no statistically significant changes to hormone levels were detected. Most commonly seen adverse events were mild gastrointestinal tract reactions. The most popularly studied formula was Kun Tai capsule and the most frequently prescribed herb was Bai shao (Paeoniae Radix Alba, Paeonia lactiflora Pall.). More than 50% included studies had low risks of bias in the domains of selection, performance, attrition and reporting.; Conclusions: This review indicated that CHM formulae were safe to be applied in MHF females and able to improve MHF-related symptom scores as well as the peripheral blood flow. Further studies should focus on specific formulae.; Competing Interests: The authors have declared that no competing interests exist.

Li, M., et al. (2022). "A systematic review on botany, processing, application, phytochemistry and pharmacological action of Radix Rehmnniae." Journal of Ethnopharmacology 285: 114820.
	Ethnopharmacological Relevance: Radix Rehmanniae (RR) is the tuber root of Rehmannia glutionsa Libosch, which was firstly recorded in Shennong's Classic of Materia Medica (⟪⟫). RR is a non-toxic and wide used traditional Chinese medicine. RR has the effect of clearing heat, generating essence, cooling blood, stopping bleeding, nourishing yin and blood, and filling marrow. It is used in clinic in the form of processed decoction pieces, including Dry Radix Rehmnniae (DRR) and Rehmanniae Radix Praeparata (RRP). The application of RR in traditional Chinese medicine (TCM) prescriptions can treat various diseases, such as anemia, irregular menstruation, deficiency of liver yin, renal failure and so on.; Aim of Review: This paper aims to provide a comprehensive and productive review of RR, which mainly contains botanical characteristics, processing methods, traditional application, chemical composition, quality control and pharmacological action.; Materials and Methods: Literature search was conducted through the Web of Science, Baidu Scholar, ScienceDirect, PubMed, CNKI, and WanFang DATA using the keywords "Radix Rehmnniae", "Rehmanniae Radix Praeparata", "processing", "clinical application", "chemical composition", "quality control", and "pharmacological action". In addition, information was collected from relevant textbooks, reviews, and documents.; Results: RR is a traditional Chinese herbal medicine with clinical value and rich resources. More than 100 components have been isolated and identified from RR. It has multiple pharmacological actions, such as hemostasis, antioxidation, anti-osteoporosis, lowering blood sugar, improving renal function, anti-inflammation, protecting neuronal function, antidepression and anti-anxiety. DRR and RRP are two different processed products of RR. After processing, there are great changes in property, taste, efficacy, clinical application, chemical composition and pharmacological action. At present, identifying chemical constituents of RR and its medicinal value has been deeply studied. However, there is a lack of research on the reasons for the differences in pharmacological effects between DRR and RRP. The reasons for these differences need to be further verified. Catalpol, the active component of RR, has been studied extensively in the literature, but the pharmacological effects of catalpol cannot represent the pharmacological effects of the whole RR. In the future, effective components such as rehmannioside D, polysaccharide, total glycosides, and effective parts in RR need to be further studied and developed. The pharmacodynamic material basis and mechanism of RR need to be further discussed. The scientific connotation and processing methods of RRP need to be studied and standardized. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Li, M., et al. (2022). "Efficacy of Autologous Intrauterine Infusion of Platelet-Rich Plasma in Patients with Unexplained Repeated Implantation Failures in Embryo Transfer: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 11(22).
	(1) Background: Controversial conclusions have been made in previous studies regarding the influence of autologous platelet-rich plasma (PRP) in the reproductive outcomes of women with repeated implantation failures (RIF) who are undergoing embryo transfer (ET). (2) Methods: This study aimed to evaluate the effect of PRP intrauterine infusion in patients with unexplained RIF, who are undergoing in vitro fertilization (IVF) or intracytoplasmic injection (ICSI), by a systematic review and meta-analysis. (3) Results: A fixed-effects model was used, and 795 cases and 834 controls were included in these studies. The pooling of the results showed the beneficial effect of PRP which were compared with those of the control in terms of the clinical pregnancy rates (n = 10, risk ratio (RR) = 1.79, 95% confidence intervals (CI): 1.55, 2.06; p < 0.01, I2 = 40%), live birth rates (n = 4, RR = 2.92, 95% CI: 2.22, 3.85; p < 0.01, I2 = 83%), implantation rates (n = 3, RR = 1.74, 95% CI: 1.34, 2.26; p < 0.01, I2 = 0%), and positive serum β-HCG 14 days after the ET (n = 8, RR = 1.77, 95% CI: 1.54, 2.03; p < 0.01, I2 = 36%). However, we did not find that the miscarriage rates indicated a significant difference between the two groups (n = 6, RR = 1.04, 95% CI: 0.72, 1.51; p = 0.83, I2 = 0%). (4) Conclusions: The findings of this systemic review and meta-analysis suggest that PRP appears to improve the results of IVF/ICSI treatments in the cases of unexplained RIF.

Li, M., et al. (2021). "The Effects of Acupuncture on Pregnancy Outcomes of Recurrent Implantation Failure: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2021: 6661235.
	Objective: To systematically evaluate the efficacy and safety of acupuncture for patients with recurrent implantation failure (RIF) undergoing in vitro fertilization-embryo transfer (IVF-ET) and hopefully provide reliable guidance for clinicians and patients.; Methods: Through searching domestic and foreign medical journals, the literature of randomized controlled trials (RCTs) of acupuncture for RIF undergoing IVF-ET was collected. RevMan 5.3 software was used for meta-analysis and Cochrane's risk of bias assessment tool was used to evaluate the quality of the included studies.; Results: Seven documents meeting the criteria were finally included. The results showed that the intervention group contributes more in outcomes including clinical pregnancy rate (RR = 1.90, 95% CI (1.51, 2.40), P < 0.05), biochemical pregnancy rate (RR = 1.59, 95% CI (1.27, 1.99), P < 0.05), embryo implantation rate (RR = 1.89, 95% CI (1.47, 2.45), P < 0.05), and endometrial thickness (MD = 1.11, 95% CI (0.59, 1.63), P < 0.05) when compared with the control group, and the difference is statistically significant. In terms of the number of embryo transfers and the type of endometrium, the difference between the acupuncture group and the control group was not statistically significant.; Conclusion: Acupuncture therapy on patients with RIF can improve the pregnancy outcome of patients. It is a relatively effective treatment with satisfactory safety and suitable for clinical application. However, as the quality of the included studies is not good enough, the conclusion of this meta-analysis should be treated with caution. More double-blind RCTs equipped with high quality and large samples are expected for the improvement of the level of evidence.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2021 Menglin Li et al.)

Li, M., et al. (2020). "Efficacy of living preparation of lactobacillus in treatment of bacterial vaginosis during pregnancy: A meta-analysis." Chinese Journal of Evidence-Based Medicine 20(8): 950-955.
	Objectives To systematically review the efficacy of living preparation of lactobacillus for bacterial vaginosis (BV) during pregnancy. Methods PubMed, Web of Science, Medline (OVID), CNKI, WanFang Data, VIP and CBM databases were electronically searched to collect randomized controlled trials (RCTs) of living preparation of lactobacillus for BV during pregnancy from inception to September 30th, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by RevMan 5.3 software. Results A total of 21 RCTs involving 2 930 patients were included. The results of meta-analysis indicated that: living preparation of lactobacillus was superior to metronidazole in effective rate (RR=1.05, 95%CI 1.02 to 1.07, P=0.000 4), premature delivery rate (RR=0.49, 95%CI 0.32 to 0.73, P=0.000 4), premature rupture of membrane rate (RR=0.54, 95%CI 0.38 to 0.77, P=0.000 7), infant of low-birth weight rate (RR=0.45, 95%CI 0.22 to 0.94, P=0.03) and puerperal infection rate (RR=0.60, 95%CI 0.39 to 0.94, P=0.03). Conclusions The current evidence shows that, living preparation of lactobacillus is superior to metronidazole for BV during pregnancy, and the incidence of adverse pregnancy outcomes (preterm delivery, premature rupture of membranes, low birth weight, puerperal infection) after treatment is lower. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.Copyright © 2020 West China University of Medical Science. All rights reserved.

Li, N., et al. (2020). "Unilateral cystectomy and serous histology are associated with relapse in borderline ovarian tumor patients with fertility-sparing surgery: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 302(5): 1063-1074.
	Purpose: Surgical procedures, histological subtypes, and surgical approaches are involved in the recurrence of borderline ovarian tumors (BOTs), but whether those three factors affect relapse remains controversial. This study aimed to explore the effects of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates of BOT after fertility-preserving surgery (FPS) according to the patients' characteristics.; Methods: A systematic search of PubMed, Embase, and the Cochrane library was conducted from their inception to November 2018. Studies that investigated the impact of surgical procedures, histological subtypes, and surgical approaches on the relapse and pregnancy rates in patients with BOT after FPS were eligible. The pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the random-effects model.; Results: Thirty-five studies involving a total of 2921 patients with BOT after FPS were included. The pooled ORs indicated that the risk of relapse was significantly increased in patients who underwent unilateral cystectomy or with serous BOT. There was no significant difference between laparoscopy and laparotomy on the risk of relapse. Surgical procedures, histological subtypes, and surgical approaches did not influence pregnancy rates.; Conclusions: Patients who underwent unilateral cystectomy or with serous BOT presented an excess risk of relapse after FPS, but the surgical approach did not affect the risk of relapse. The pregnancy rate is not affected by surgical procedures, histological subtypes, and surgical approaches.

Li, N. J., et al. (2023). "Anti-mullerian hormone as a predictor for live birth among women undergoing IVF/ICSI in different age groups: an update of systematic review and meta-analysis." Archives of Gynecology and Obstetrics 308(1): 43-61.
	Purpose: To update the evidence of anti-mullerian hormone (AMH) as predictive factors for live birth outcome in women undergoing assisted conception and discover the modulating effect of age. Method(s): PubMed, Embase, Medline, and Web of Science were searched for studies published until June 2021. We included studies that measured serum AMH levels and reported the subsequent live birth outcomes. Random effects models and hierarchical summary receiver operating characteristics (HSROC) models were used. The QUADAS-2 checklist was employed to assess the quality of the included studies. Result(s): We included 27 studies (27,029 women) investigating the relationship between AMH and live birth outcome after assisted conception. The diagnostic odds ratios (DOR) from random effects models were ruled out due to high heterogeneity. Our findings suggested that AMH was associated with live birth. The DOR was 2.21 (95% CI 1.89-2.59), and 2.49 (95% CI 1.26-4.91) for studies on women with unspecified ovarian reserve and women with low ovarian reserve, respectively. The DOR of those with advanced ages was 2.50 (95% CI 1.87-2.60). For younger women, the DOR was 1.41 (95% CI 0.99-2.02). HSROCs showed that AMH had no predictive ability towards live birth in women with diminished ovarian reserve or younger age. Exclusion of Chinese cohorts lowered the heterogeneity. Conclusion(s): This study revealed that AMH had better prediction for live birth in advanced-age women. AMH may have implicative predictive value for assisted conception counseling of couples of advanced ages.Copyright © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Li, P.-P., et al. (2019). "[Systemic evaluation and Meta-analysis of efficacy and safety of Kangfu Xiaoyan Suppository in treatment of pelvic inflammatory disease]." Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 44(22): 4962-4974.
	To evaluate the efficacy and safety of Kangfu Xiaoyan Suppository in the treatment of pelvic inflammatory disease. Four Chinese databases,namely CNKI,VIP,WanFang and SinoMed,and three English databases Cochrane Library,namely Medline,and ClinicalTrail.gov were systematically and comprehensively retrieved from the establishment of each database to June 2018. The quality of the included studies was evaluated by using the risk assessment tools developed by the Cochrane Collaboration,and RevMan 5. 3 software was used for Meta-analysis. A total of 675 articles were retrieved,and finally 56 studies were included. The total sample size was 6 228,the test group included 3 267 cases,and the control group included 2 961 cases. The overall quality of the included studies was generally low. According to the intervention measures and outcome indicators,the included studies were divided into different subgroups for analysis. The main results of Meta-analysis showed that the recurrence rate of Kangfu Xiaoyan Suppository combined with antibiotics was lower than that of antibiotics alone. Kangfu Xiaoyan Suppository combined with antibiotics was superior to antibiotics alone in terms of abdominal pain,leucorrhea abnormality relief time,mass absorption time and pain relief time. In terms of safety,Kangfu Xiaoyan Suppository combined with antibiotics had a lower incidence of adverse reactions than antibiotics alone. Based on the results of this study,it is indicated that Kangfu Xiaoyan Suppository had a certain effect on the treatment of pelvic inflammatory disease,especially with a lower recurrence rate. The long-term effect is remarkable. No serious adverse reaction was observed. Restricted by the quality of the studies included,the above conclusion need to be further verified in high-quality,largesize,multi-center clinical researches.

Li, Q., et al. (2023). "Comparative efficacy of Chinese herbal injections for treating endometrial carcinoma: A Bayesian network meta-analysis." Medicine 102(41): e34676.
	Background: In view of the limitations of chemotherapy (CT) for endometrial carcinoma (EC) and the extensive use of Chinese herbal injections (CHIs), this network meta-analysis (NMA) compared the efficacy and safety of 6 CHIs combined with CT for EC.; Methods: Several electronic databases were searched for randomized controlled trials (RCTs). The retrieval period was from the establishment of the databases to September 18, 2022. The quality of the literature was assessed after data extraction using Review Manager version 5.4. The Stata 13.1 and OpenBUGS3.2.3 software were used for data analysis. Cluster analysis was performed to compare the effect of CHIs between 2 different outcomes.; Results: A total of 25 RCTs with 2023 patients were included. The findings demonstrated that when combined with CT, Aidi, Compound Kushen, Kangai, Eshuyou injection, and Shenmai injection can increase clinical efficacy compared to chemotherapy alone. The KPS level can be raised with aidi injection. Combining CT with injections of Aidi, Shenmai, Huangqi, and Compound Kushen can improve immunological performance. Combining CT with injections of Aidi, Huangqi, and Compound Kushen can lower serum amounts of tumor markers. Kangai injection was regarded as a good option for minimizing negative responses. According to the cluster analysis, the clinical effective rate, the KPS score, the level of CA125, and the clinical effective rate of Kangai injection and Aidi injection combined with CT were all better.; Conclusion: Current evidence revealed that CHIs combined with CT have a better impact on patients with EC than CT alone. It's possible that KangAi, Aidi, and Eshuyou infusion are the best CHIs for EC. Additionally, more high-quality RCTs are required in order to further corroborate the findings due to NMA's limitations.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Li, Q., et al. (2022). "Short-term Outcomes of Acupuncture Interventions on Uterine Adenomyosis: A Systematic Review and Meta-analysis." Acupuncture and Electro-Therapeutics Research 47(2): 203-214.
	The purpose of this systematic review is to evaluate for evidence of the association of acupuncture with relieving the symptoms of adenomyosis. We searched ten electronic databases and included randomized controlled trials (RCTs) in women with adenomyosis. The methodological quality was moderate evidence level by Cochrane risk-of-bias criteria. The results were analyzed by Review Manager 5.3 and expressed as standardized mean differences (SMD) or mean differences (MD). Eleven RCTs (942 subjects) were included in this meta-analysis. Analysis with no heterogeneity showed that acupuncture group obtained a significant better effect (95% CI, -0.48 to -0.10; I2 = 0%) on reducing the size of the uterus and was superior in the shrink of carbohydrate antigen 125 (CA125) level (95% CI, -1.13 to -0.44; I2 = 0%) than that in pharmacological medicine alone group. Moreover, acupuncture was significantly associated with improving patients' dysmenorrheal symptoms after 3-month menstrual cycles treatment (95% CI -1.25 to -0.13). The adverse events, especially the incidence of hot flashes, were less reported in acupuncture group compared to pharmacological medicine alone group (Odds Ratio, OR, 0.17; 95% CI, 0.08 to 0.35; I2 = 0%). Acupuncture therapy is a promising avenue for the development of alternatives to surgery and medicine in the treatment of adenomyosis. However, further rigorous trials are needed to confirm the claims of our results.Copyright © 2022 Cognizant Communication Corporation. All rights reserved.

Li, Q., et al. (2021). "Efficacy of Chinese herbal prescriptions containing Ejiao or Velvet antler for management of uterine fibroids: a systematic review and meta-analysis of randomized controlled trials." Annals of Palliative Medicine 10(8): 8772-8786.
	Background: To evaluate the efficacy and safety of the controversial Chinese herbal prescriptions containing Ejiao or Velvet antler (VA) in the treatment of uterine fibroids.; Methods: We searched 4 famous Chinese databases, the Chinese Clinical Trial Registry, PubMed, Cochrane Central, Google Scholar, Embase, and J-STAGE up to July 2019. We included all eligible randomized controlled trials (RCTs) which compared Chinese herbal prescriptions containing Ejiao or VA (E/VA) with placebo, pharmaceutical intervention, surgery, or other traditional Chinese medicines (TCMs) for uterine fibroids and assessed the risk of bias according to the Cochrane Collaboration's tool. The software Review Manager (RevMan) 5.1 was used for data analysis.; Results: A total of 9 RCTs involving 844 patients were identified. Meta-analyses demonstrated that TCM (E/VA) plus mifepristone reduced the volume of uterine fibroids to a greater degree than mifepristone alone [standardized mean difference (SMD): 0.59, 95% CI: 0.33 to 0.85, P<0.00001, I2=50%]; TCM (E/VA) did not enlarge the volume of fibroids when menopausal hormone therapy (MHT) significantly increased the volume (SMD: 1.06, 95% CI: 0.73 to 1.38, P<0.00001, I2=0. The uterine volume change difference was larger via combination therapy of TCM (E/VA) and mifepristone than that of mifepristone (SMD: 0.29, 95% CI: 0.09 to 0.49, P=0.005, I2=0%). The TCM (E/VA) group of had an advantage over the control group in the improvement of fibroid-related symptoms [relative risk (RR): 1.24, 95% CI: 1.15 to 1.35, P<0.00001, I2=0%]. It was found that TCM (E/VA) plus mifepristone could lower estradiol (E2) levels to a greater degree than mifepristone alone (SMD: 1.63, 95% CI: 0.42 to 2.83, P=0.008, I2=97%), as well as progesterone (P) level (SMD: 0.79, 95% CI: 0.55 to 1.04, P<0.00001, I2=43%) in non-menopausal women. A total of 5 studies reported adverse events (AEs), the TCM (E/VA) group was potentially safer than the control group, with lower incidence of AEs (RR: 0.24, 95% CI: 0.15 to 0.40, P<0.00001, I2=25.8%).; Discussion: TCM prescriptions containing E/VA seemed superior to the control group in shrinking the volume of uterine fibroids and uterus, improving related symptoms, and reducing non-menopausal women's E2 and P levels, with lower incidence of AEs.

Li, S., et al. (2023). "Role of Adjuvant Chemotherapy in Stage I Pure Ovarian Immature Teratoma: A Systematic Review and Meta-Analysis." Cancers 15(6).
	To determine the role of adjuvant chemotherapy in stage IA G2-3 and stage IB-IC pure ovarian immature teratoma (POIT), we performed a systematic review and meta-analysis by searching PubMed, Embase, Cochrane library, Web of Science, and ClinicalTrials.gov. Randomized controlled trials or cohort studies on stage IA G2-G3 or stage IB-IC POIT between 1 January 1970 and 15 December 2022 were enrolled. The recurrence rate and mortality rate were the primary outcomes, and subgroup analysis based on the tumor stage and grade was also conducted. In total, 15 studies with 707 patients were included. Compared with surveillance, adjuvant chemotherapy significantly decreased the mortality rate (RR 0.31, 95% CI 0.11-0.88, p = 0.03), but not recurrence (RR 0.74, 95% CI 0.39-1.42, p = 0.37), in the overall population. Subgroup analysis showed no statistical difference in the recurrence rate and mortality rate between patients who received adjuvant chemotherapy and surveillance in pediatric POIT, stage IA G2-3 POIT, stage IB-IC POIT, and stage IA-IC G3 POIT (all with p > 0.05). However, patients who underwent adjuvant chemotherapy appeared to have a lower risk of both recurrence (RR 0.17, 95% CI 0.03-0.83, p = 0.03) and death (RR 0.04, 95% CI 0.00-1.00, p = 0.05) in adult POIT. Adjuvant chemotherapy significantly decreased the mortality rate in patients with stage I POIT and lowered the risk of recurrence in the adult subgroup. Surveillance administered in stage I POIT over IA G1 should be cautious, especially in adult patients.

Li, S., et al. (2019). "Effect of acupuncture on insomnia in menopausal women: a study protocol for a randomized controlled trial." Trials 20(1): 308.
	Background: The National Institutes of Health estimates the prevalence of insomnia in menopausal women at 40-50%. Some studies have shown that acupuncture might be effective in treating primary insomnia and insomnia related to depression and stroke. Although there are some programs supporting insomnia during the menopausal transition, there are few randomized controlled trials (RCT) to provide evidence regarding their effectiveness. We design a RCT of suitable sample size to verify the effectiveness of acupuncture in patients with insomnia during the menopausal transition and to form an optimized acupuncture treatment protocol.; Method/design: In this randomized, single-site, single-blind, placebo-controlled trial, 84 eligible patients will be recruited and randomly assigned to either the acupuncture group (n = 42) or the sham control group (n = 42) in a 1:1 ratio. Participants will receive a total of 18 treatment sessions for eight consecutive weeks. Treatments will be given three times per week in the first four weeks, twice a week for the next two weeks, and finally once weekly for the final two weeks. Treatment will utilize eight main acupoints (GV20, GV24, GV29, RN6, RN4, SP6, HT7, EX-HN22) and extra two acupoints based on syndrome differentiation. The primary outcome will be assessed using the Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes will be measured by sleep parameters recorded in the Actigraphy (SE, TST, SA), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Menopause Quality of Life (Men-QOL). The primary outcomes will be assessed at baseline, week 4, week 8, and the first and third month after the end of treatment.; Discussion: If the results confirm that acupuncture is effective and safe for the treatment on insomnia in menopausal women, this positive outcome could provide evidence for clinical application.; Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800018645 . Registered on 10 January 2018.

Li, T., et al. (2021). "Quantitative study on the efficacy of acupuncture in the treatment of menopausal hot flashes and its comparison with nonhormonal drugs." Menopause (New York, N.Y.) 28(5): 564-572.
	OBJECTIVE: This study aimed to compare the efficacy of acupuncture to that of sham acupuncture, placebo pills, and nonhormonal drugs to provide the necessary quantitative information for establishing medication guidelines for menopausal hot flashes. METHODS: A comprehensive literature search was performed using public databases. Randomized clinical studies on acupuncture therapy for the treatment of hot flashes in menopausal women were identified. A time-course model was established to describe the efficacy characteristics of acupuncture and sham acupuncture, which were compared with the efficacy of nonhormonal drugs and placebo pills reported in the literature. RESULTS: A total of 17 studies involving 1,123 participants were included. The quality of all the studies included in the analysis is medium to high, and there was no obvious risk of bias. It was found that the baseline number of hot flashes was an important factor affecting the efficacy of acupuncture and sham acupuncture. After correcting the baseline to eight hot flashes per day, the frequency of hot flashes decreased from baseline for traditional acupuncture (TA), electro-acupuncture (EA), TA&EA (merger analysis of TA and electro-acupuncture), and sham acupuncture were 3.1 (95% confidence interval [CI]: 2.8-3.4), 3.6 (95% CI: 3.2-4.0), 3.2 (95% CI: 2.9-3.5), and 2.6 (95% CI: 2.2-3.0) times/d at week 8, respectively. Compared with findings reported in the literature, we found the efficacy of electro-acupuncture was comparable to that of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and neuroleptic agents such as gabapentin and escitalopram. Furthermore, the efficacy of TA&EA (merged) was significantly higher than that of placebo pills (2.3, 95% CI: 1.8-2.9). CONCLUSIONS: The efficacy of TA&EA (merged) was higher than that of sham acupuncture and significantly higher than that of placebo pills. The efficacy of electro-acupuncture was higher than that of traditional acupuncture, significantly higher than that of sham acupuncture, and comparable to that of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and neuroleptic agents.

Li, W. (2022). "Meta-analysis of endometrioma surgery on antral follicle count and anti-Müllerian hormone: individual participant data and sophisticated analysis strategy are needed." American Journal of Obstetrics and Gynecology 226(1): 158.
	
Li, W., et al. (2020). "Interventional embolization, surgery and high intensity focused ultrasound for the treatment of uterine fibroids: A network meta-analysis." Chinese Journal of Evidence-Based Medicine 20(4): 458-465.
	Objectives To systematically review the safety and effectiveness of uterine artery embolization (UAE), surgery and high intensity focused ultrasound (HIFU) in the treatment of uterine fibroids. Methods PubMed, EMbase, The Cochrane Library, Web of Science, WanFang Data and CNKI databases were electronically searched to collect relevant studies on comparing the safety and effectiveness of UAE, surgery and HIFU in the treatment of uterine fibroids from January 2000 to August 2019. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias of included studies, network meta-analysis was performed by ADDIS 1.16.8 software and Stata 14.0 software. Results A total of 11 trials (22 references) involving 3469 patients were included. Compared with surgery, UAE and HIFU patients had higher quality of life (1-year follow-up) improvement, and UAE was higher than HIFU. Network meta-analysis showed that patients treated with HIFU had the lowest incidence of major complications within 1 year, followed by UAE, and surgery. Patients treated with HIFU and UAE had shorter hospitalization and quicker recovery time than surgery. The rate of further intervention after surgery treatment might be lower than that of UAE and HIFU. Conclusions UAE has the highest quality of life improvement (1-year follow-up) for uterine fibroids. HIFU and UAE are safer with shorter hospital stays and quicker recovery time compared with surgery. However, both UAE and HIFU have the risk of re-treatment. However, limited by the number and quality of included studies, the above conclusions are needed to be verified by more high-quality studies.Copyright © 2020 West China University of Medical Science. All rights reserved.

Li, W., et al. (2019). "Effectiveness of Acupuncture Used for the Management of Postpartum Depression: A Systematic Review and Meta-Analysis." BioMed Research International 2019: 6597503.
	Background: Previous studies have demonstrated that acupuncture was an effective alternative for treating major depressive disorders. However, the use of acupuncture for the treatment of postpartum depression remains controversial. This review summarizes the most significant studies in the area of acupuncture treatment for postpartum depression and provides a detailed overview of the efficacy of acupuncture for the treatment of postpartum depression.; Methods: We undertook a systematic review of publicly available electronic databases to identify studies that evaluated acupuncture for the treatment of postpartum depression. Our meta-analysis selected randomized controlled trials (RCTs) and quasi-RCTs that reported on the treatment effect of acupuncture on postpartum depression.; Results: Eight prospective trials reporting data on postpartum depression were included in our meta-analysis. The results demonstrated that acupuncture treatment could significantly reduce HAMD scores (SMD: -1.08; 95%CI: -2.11 to -0.05; P=0.040). However, with regard to EPDS, clinical response, and serum estradiol levels, pooled analysis suggested no beneficial effects of acupuncture for postpartum women in EPDS (RR: 1.23; 95%CI: 0.90 to 1.67; P=0.195); clinical response (RR: 1.00; 95%CI: 0.89 to 1.12; P=0.969); and the levels of serum estradiol (SMD: 1.96; 95%CI: -0.01 to 3.93; P=0.051).; Limitations: First, there was relatively high heterogeneity among the studies, except for clinical response. In order to identify the sources of heterogeneity, we divided the studies into subgroups by way of controls. However, heterogeneity still existed, which suggested that it arose from participants rather than controls. Second, the sample size of the studies was small, causing the power of summary results to be low. This may result in over- or underestimating the interpretation of the results. Third, our analysis used pooled data, which restricted us from performing a more detailed analysis.; Conclusions: Our meta-analysis suggested that acupuncture treatment may reduce HAMD scores, while no significant effects on EPDS, clinical response, and serum estradiol levels were observed.

Li, X., et al. (2023). "The effects of light therapy on depression and sleep in women during pregnancy or the postpartum period: A systematic review and meta-analysis." Brain and Behavior 13(12): e3339.
	Background: In recent years, light therapy has been tried for the treatment of depression and sleep in pregnancy or postnatal period women, but the results have been inconclusive. This meta-analysis is the first to systematically review the effects of light therapy on depression and sleep disturbances in women during pregnancy and the postnatal period. Method(s): We searched for randomized controlled studies in PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical Database up to January 2023. The standardized mean difference (SMD) was used to assess the efficacy of the outcome indicators. Result(s): Eight studies were eventually included in the analysis. The results showed that light therapy was more effective than the placebo group in terms of depression (SMD =.34, CI =.08-.61) and sleep (SMD =.64,95%CI =.28-1.00). Subgroup analysis could not explain the significant heterogeneity. There were no serious adverse effects in either the light therapy or placebo groups. Conclusion(s): Light therapy could be considered an effective treatment for depression and sleep disturbances in women during pregnancy and the postnatal period. However, future high-quality trials with larger sample sizes are still needed.Copyright © 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Li, X., et al. (2021). "The effect of metformin on homocysteine levels in patients with polycystic ovary syndrome: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 47(5): 1804-1816.
	Purpose: Metformin is widely used as an insulin sensitizer in polycystic ovary syndrome (PCOS) patients. However, previous studies have found that the effect of metformin on the level of homocysteine were not consistent in PCOS patients. The aim of this review was to analyze the effect of metformin on homocysteine levels in patients with PCOS patients.; Methods: The Cochrane Library, Pubmed, and Web of Science were searched according to predefined search terms. There is no restriction for publication time and language.; Results: Eleven studies were included and the data were extracted. The homocysteine level in PCOS patients was significantly increased after taking metformin (mean difference [MD] -1.33; 95% confidence interval [CI] -2.16 to -0.49, p = 0.002). Subgroup analysis showed that the level of homocysteine was generally increased in PCOS patients with body mass index (BMI) ≥25 after taking metformin alone (MD -1.82; 95% CI -2.56 to -1.07, p < 0.00001). There was no significant change in homocysteine level in PCOS patients with BMI <25 (MD 0.69; 95% CI -0.41 to 1.79, p = 0.22). Subgroup analysis showed that there was no significant difference when taking metformin >3 months or taking metformin ≤3 months (p = 0.84). Taking metformin ≥1700 mg/days significantly increased homocysteine levels in PCOS patients (MD -2.05; 95% CI -2.40 to -1.70, p < 0.00001). When taking metformin <1700 mg/days, there was no significant difference in homocysteine level in PCOS patients (MD 0.15; 95% CI -1.06 to 1.37, p = 0.80). The difference between the two subgroups was significant (p = 0.0006). There was no significant difference in vitamin B12 level before and after metformin treatment (MD 24.70; 95% CI -22.54 to 71.93, p = 0.31). There was a decrease in serum folic acid level after metformin administration (MD 1.03; 95% CI 0.80 to 1.26, p < 0.00001).; Conclusion: Taking metformin alone increased homocysteine levels and decreased folic acid levels in nonpregnant PCOS patients. And, it was suggested that the dosage of metformin should be less than 1700 mg/days. The supplement of folic acid and B vitamins during metformin administration may be essential in nonpregnant PCOS patients. We should pay much attention to the potential effect of metformin in PCOS patients. (© 2021 Japan Society of Obstetrics and Gynecology.)

Li, X., et al. (2022). "Effectiveness of cognitive behavioral therapy for perinatal maternal depression, anxiety and stress: A systematic review and meta-analysis of randomized controlled trials." Clinical psychology review 92: 102129.
	Cognitive behavioral therapy (CBT) has been widely studied in prenatal or postnatal depression, with much less research on anxiety and stress. This meta-analysis aims to comprehensively evaluate CBT efficacy for perinatal depression, anxiety and stress in the short term (from baseline to immediately post-intervention) and in the long term (from baseline to the end of follow-up). Five databases were searched. We included 79 randomized controlled trials (RCTs) and quasi-RCTs assessing the efficacy of CBT during pregnancy and the first year postpartum. Primary outcome was the mean score change in depression, anxiety and stress. CBT-only and CBT plus other interventions were effective for perinatal maternal depression in the short term (SMD -0.69, 95% CI: -0.83, -0.55) and long term (SMD -0.59, 95% CI -0.75, -0.42). CBT-only had both short- and long-term efficacy for perinatal anxiety (short term: SMD -0.63, 95% CI -0.85, -0.42; long term: SMD -0.71, 95% CI -1.02, -0.39) and short-term efficacy for perinatal stress (SMD -0.96, 95% CI -1.40, -0.52). Overall, CBT was effective for perinatal maternal depression, anxiety and stress. CBT-only exhibited short-term efficacy for perinatal depression, anxiety and stress, and long-term efficacy for perinatal depression and anxiety. Subgroup analyses suggested that CBT-only was effective across a wide variety of modalities. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Li, X., et al. (2021). "Aidi injection, a traditional Chinese biomedical preparation for gynecologic tumors: a systematic review and PRISMA-compliant meta-analysis." Bioscience reports 41(3).
	Aidi injection (ADI), a traditional Chinese biomedical preparation, is a promising adjuvant therapy for gynecologic tumors (GTs), including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC). Although studies have reported positively on ADI therapy, its exact effects and safety in GT patients remain controversial. Therefore, a wide-ranging systematic search of electronic databases was performed for this meta-analysis. Data from 38 trials including 3309 GT patients were analyzed. The results indicated that the combination of conventional treatment and ADI markedly improved the patients' overall response rate (P<0.00001), disease control rate (P<0.00001), and quality of life (P<0.05) compared with conventional treatment alone. Furthermore, patient immunity was enhanced with combined treatment, as indicated by significantly increased percentages of CD3+ (P=0.005) and CD4+ (P<0.00001) and increased CD4+/CD8+ ratio (P=0.001). Most of the adverse events caused by radiochemotherapy such as gastrointestinal issues, leukopenia, thrombocytopenia, and hepatotoxicity, (P<0.05 for all) were significantly alleviated when ADI was used in the GT patients. However, other adverse events such as nephrotoxicity, diarrhea, alopecia, and neurotoxicity did not significantly differ between the two groups. Overall, these results suggest that the combination of conventional and ADI treatment is more effective than conventional treatment alone. (© 2021 The Author(s).)

Li, X., et al. (2023). "Ginseng and Ginseng Herbal Formulas for Symptomatic Management of Fatigue: A Systematic Review and Meta-Analysis." Journal of Integrative and Complementary Medicine 29(8): 468-482.
	Objectives: Ginseng has been widely used in fatigue management. However, its efficacy on fatigue remains unclear. This study aimed to assess the efficacy and safety of ginseng and ginseng herbal formulas for fatigue in randomized clinical trials (RCTs). Method(s): The authors searched PubMed, Embase, Cochrane, Web of Science, and Allied and Complementary Medicine Database (AMED) databases from inception to July 6, 2022. Outcomes included fatigue severity, quality of life (QoL), and adverse events (AEs). Quality of evidence was assessed using the Cochrane Risk of Bias Tool. They pooled all included data and performed subgroup analysis by fatigue type, assessment instrument, and ginseng type. Result(s): The authors included 19 RCTs. Pooled analyses found no significant reduction in fatigue severity with ginseng versus controls (standardized mean difference [SMD]: -0.36, 95% confidence interval [CI]: -0.82 to 0.11, p = 0.13). In subgroup analysis, there was significant fatigue reduction with the ginseng herbal formula (SMD: -0.39, 95% CI: -0.66 to -0.13, p = 0.004) and chronic fatigue (CF) (SMD: -0.30, 95% CI: -0.56 to -0.03, p = 0.03) compared to controls. Ginseng produced significant reductions in general (i.e., non-disease-specific) fatigue compared to controls (SMD: -0.48, 95% CI: -0.71 to -0.25, p < 0.0001). Ginseng was associated with a trend toward QoL improvement (p = 0.05) and did not increase AEs compared with controls. Effect sizes were small. Conclusion(s): Ginseng herbal formulas improved fatigue severity compared to controls, especially among patients with CF, but with a small effect size. Rigorous RCTs as well as guidelines for standard ginseng usage are needed to further evaluate the effects of ginseng for fatigue and ensure proper use.Copyright © 2023 Mary Ann Liebert, Inc.

Li, X., et al. (2021). "Granulosa cells apoptosis and follicular fluid hormones: comparison of progestin-primed ovarian stimulation versus GnRH antagonist protocols." Gynecological Endocrinology 37(7): 609‐613.
	OBJECTIVE: To explore the effect of progestin‐primed ovarian stimulation protocol (PPOS) on mural granulosa cells (GCs) apoptosis and hormonal profiles in follicular fluid (FF) and efficacy over GnRH antagonist (GnRH‐A) protocols. METHODS: We performed a prospective cohort study from June through August 2017 at a tertiary teaching hospital. 63 Patients meeting our criteria were recruited in this prospective study voluntarily and stratified to PPOS or GnRH‐A group randomly. Mural GCs and FF were collected during oocyte retrieval. Apoptosis of GCs was assessed using the Annexin V‐affinity assay by flow cytometry and hormonal profiles in FF were measured using electrochemiluminescence. RESULTS: A total of 63 women were assessed for eligibility, with 25 cases in PPOS group and 38 in GnRH‐A group. Difference of early stage apoptosis rate, late stage apoptosis rate, and total apoptosis rate did not reach statistical significance between groups. Meanwhile, concentrations of hormones in FF were comparable in two groups. No statistically significant differences were observed in number of oocytes retrieved, mature oocyte rate, fertilization rate, and top‐quality embryos rate. No patients experienced premature LH surge in both groups during the study. CONCLUSION: Compared to GnRH antagonist protocol, PPOS had comparable laboratory outcomes, GCs apoptosis rate and hormonal profiles in FF. PPOS is an effective and safe alternative option to provide controlled ovarian hyperstimulation (COH).

Li Xing, L., et al. (2022). "Nonpharmacological Interventions for primary dysmenorrhea: A Systematic Review and Network Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	Review question The aim of this network meta-analysis of randomized controlled trials is to evaluate the efficacy and safety of nonpharmacological interventions for primary dysmenorrhea Searches We will search articles in three electronic database including PubMed, EMBASE and Cochrane Library. All the English publications until 30 June 2022 will be searched without any restriction of countries or article type. We will apply a combination of Medical Subject Heading (MeSH) and free-text terms incorporating database specifific controlled vocabularies and text words to implement search strategies. Types of study to be included Radomized controlled trials (RCTs) will be included Condition or domain being studied Primary dysmenorrhoea is a common, idiopathic, chronic pelvic pain syndrome, almost 45% to 90% of women experience some menstrual pain. pharmacological interventions including nonsteroidal antiinflflammatory drugs (NSAIDs) and hormonal contraceptives have been the mainstay of treatment for PD, Non-drug treatments, including alternative and physical therapies, are increasingly being used for dysmenorrhoea, their effectiveness is still being debated. Participants/population All relevant RCTs using Transcutaneous electrical nerve stimulation or complementary and alternative therapies for PD will be included. Quasi-RCTs, abstracts, conference abstracts, editorials, letters to the editor, and case reports will be excluded such as those allocating by medical record number.The study population consisted of adult patients who had been diagnosed with cancer-related fatigue either during or after cancer treatment. Intervention(s), exposure(s) Transcutaneous electrical nerve stimulation, Acupressure, Spinal manipulation, Acupuncture, Topical heat, Fish oil, Herbal medicine Comparator(s)/control placebo, usual care control, no intervention, wait-list control Main outcome(s) Pain intensity（such as VAS） Additional outcome(s) The secondary outcomes are quality of life, clinical effective rate, and adverse events. Quality of life of women with PD could be measured by various questionnaires such as Short-Form Health 12, Short-Form Health 36 questionnaire Data extraction (selection and coding) Two authors will independently extract data. Any disagreement will be resolved by discussion until consensus is reached or by consulting a third author.The following data will be extracted: title, fifirst author, year of publication, journal, registration number to trials registries, country of conduct, number of study arms, method of randomization and blinding, country of conduct, number of centers, and funding/ sponsor. Risk of bias (quality) assessment 27.Risk of bias in the eligible studies will be assessed by the Cochrane Collaboration’s risk of bias tool, which consists of 7 domains of bias relevant to the quality of RCTs.The criteria to be assessed include the following domains: random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessors, incomplete outcome data, selective reporting, and other sources of bias. An assessment of risk of bias will be made for the eligible studies based on the following three levels: “low risk of bias,” “unclear risk of bias,” “high risk of bias.” Strategy for data synthesis The network meta-analysis was performed with Aggregate Data Drug Information System (ADDIS) version 1.16.8 (https://addis.drugis.org). This software package is based on the Bayesian framework and Markov chain Monte Carlo method, which can evaluate and process research data a priori.The consistency test was judged by either node-splitting analysis or inconsistency standard deviation (ISD). Analysis of subgroups or subsets We will explore the sensitivity of our conclusions for the 2 primary outcomes, and the sensitivity will be analyzed by excluding the following aspects: 1. Studies with high risk of bias 2. Open studies 3. Studies providing published data only 4. Studies with unfair dose comparisons Contact details for further information li xing lin 543944396@qq.com Organisational affiliation of the review Guangzhou university of Chinese Traditional Medicine Review team members and their organisational affiliations Mr li xing lin. Guangzhou university of Chinese Traditional Medicine Mrs xinyu hao. Mr junren lin. Mr zhanmou liang. Type and method of review Network meta-analysis, Systematic review Anticipated or actual start date 30 June 2022 Anticipated completion date 30 October 2022 Funding sources/sponsors None Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Dysmenorrhea; Female; Humans; Network Meta-Analysis Date of registration in PROSPERO 14 August 2022 Date of first submission 03 August 2022

Li, Y. (2023). "Efficacy and safety of PARP inhibitors for maintenance treatment of ovarian cancer, regardless of BRCA or HRD status: a comprehensive updated meta-analysis." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 43(1): 2171282.
	Without taking into account existing biomarkers like genetic mutations (BRCA mutation, Homologous recombination deficiency) with advanced ovarian cancer (OC), the overall survival (OS), progress-free survival (PFS) of the aggregate all groups that have been classified were hazard ratio (HR): 0.72, 95% confidence intervals (CI): 0.66-0.79 and HR: 0.48, 95%CI: 0.44-0.52, respectively. Meanwhile, the OS and PFS of the whole population (regardless of existing genetic mutation markers) were HR: 0.74, 95%CI: 0.64-0.87 and HR: 0.52, 95%CI: 0.42-0.65, separately. Furthermore, the OS and PFS of positive gene mutation markers were HR: 0.71, 95%CI: 0.61-0.83 (HRD and BRACm) and HR: 0.47, 95%CI: 0.42-0.52 (HRD and BRACm), individually. The poly ADP-ribose polymers (PARP) inhibitors have desired efficiency and security in the maintenance treatment of advanced OC patients with BRCAm or BRCAwt, HRD or HRP and unknown gene status.

Li, Y., et al. (2023). "Efficacy of non-invasive photodynamic therapy for female lower reproductive tract diseases associated with HPV infection: a comprehensive meta-analysis." Lasers in Medical Science 38(1): 42.
	Photodynamic therapy (PDT) is a proposed non-invasive, highly effective, and fertility-preserving method for the treatment of lower reproductive tract diseases in women. We aim to evaluate the effect of PDT on complete remission, recurrence, and HPV clearance in diseases of the female lower reproductive tract associated with the human papillomavirus (HPV) infection in this meta-analysis. PubMed, EMBASE, Scopus, Cochrane Library, and China National Knowledge Infrastructure databases were searched to compare PDT with other treatments for complete remission, recurrence, and HPV clearance in women with lower genital tract disease. Fixed or random effect models were performed to assess the pooled effect size. Sensitivity analysis was performed to detect heterogeneity in the included studies. The Begg and Egger test assessed publication bias. There were 12 studies qualified for inclusion; compared to other treatments, PDT had a significant advantage in complete remission (OR=2.97, 95%CI, 2.18-4.04, I2=0, P<0. 001) and recurrence (OR, 0.21; 95%CI, 0.11-0.39; I2=34.9%, P<0. 001). Furthermore, PDT clears HPV quickly and lastingly compared to other therapies (OR, 2.65; 95% CI, 1.41-4.95; I2=71.0%, P=0.002). In addition, the heterogeneity test of sensitivity analysis suggested that the results were robust. Begg test (P=0.73) and Egger test (P=0.71) showed no publication bias. PDT treats diseases of the female lower reproductive tract associated with HPV infection: high complete remission, low recurrence, and rapid and lasting HPV clearance. The PDT seems to be a non-invasive, effective, and promising treatment of female lower reproductive tract diseases associated with HPV infection.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.

Li, Y., et al. (2021). "Comparison of the complications between minimally invasive surgery and open surgical treatments for early-stage cervical cancer: A systematic review and meta-analysis." PloS One 16(7): e0253143.
	Background: This meta-analysis comprehensively compared intraoperative and postoperative complications between minimally invasive surgery (MIS) and laparotomy in the management of cervical cancer. Even though the advantages of laparotomy over MIS in disease-free survival and overall survival for management of gynecological diseases have been cited in the literature, there is a lack of substantial evidence of the advantage of one surgical modality over another, and it is uncertain whether MIS is justifiable in terms of safety and efficacy.; Methods: In this meta-analysis, the studies were abstracted that the outcomes of complications to compare MIS (laparoscopic or robot-assisted) and open radical hysterectomy in patients with early-stage (International Federation of Gynecology and Obstetrics classification stage IA1-IIB) cervical cancer. The primary outcomes were intraoperative overall complications, as well as postoperative aggregate complications. Secondary outcomes included the individual complications. Two investigators independently performed the screening and data extraction. All articles that met the eligibility criteria were included in this meta-analysis.; Results: The meta-analysis finally included 39 non-randomized studies and 1 randomized controlled trial (8 studies were conducted on robotic radical hysterectomy (RRH) vs open radical hysterectomy (ORH), 27 studies were conducted on laparoscopic radical hysterectomy (LRH) vs ORH, and 5 studies were conducted on all three approaches). Pooled analyses showed that MIS was associated with higher risk of intraoperative overall complications (OR = 1.41, 95% CI = 1.07-1.86, P<0.05) in comparison with ORH. However, compared to ORH, MIS was associated with significantly lower risk of postoperative aggregate complications (OR = 0.40, 95% CI = 0.34-0.48, P = 0.0143). In terms of individual complications, MIS appeared to have a positive effect in decreasing the complications of transfusion, wound infection, pelvic infection and abscess, lymphedema, intestinal obstruction, pulmonary embolism, deep vein thrombosis, and urinary tract infection. Furthermore, MIS had a negative effect in increasing the complications of cystotomy, bowel injury, subcutaneous emphysema, and fistula.; Conclusions: Our meta-analysis demonstrates that MIS is superior to laparotomy, with fewer postoperative overall complications (wound infection, pelvic infection and abscess, lymphedema, intestinal obstruction, pulmonary embolism, and urinary tract infection). However, MIS is associated with a higher risk of intraoperative aggregate complications (cystotomy, bowel injury, and subcutaneous emphysema) and postoperative fistula complications.; Competing Interests: The authors have declared that no competing interests exist.

Li, Y., et al. (2023). "Comparison of efficacy of single-port versus conventional laparoscopic treatment for uterine leiomyoma: a latest meta-analysis." Frontiers in Oncology 13: 1192582.
	Objective: Single-port laparoscopy has been proposed as an ideal surgical method for the treatment of uterine leiomyoma. It can effectively remove the lesion, reduce the loss of hemoglobin, and has superior cosmetic effects. Therefore, we searched relevant studies and conducted a meta-analysis to evaluate the effect of single-port laparoscopy on myoma resection, hemoglobin loss, and scar beauty compared to conventional laparoscopy.; Methods: We systematically searched PubMed, EMBASE, scope, Cochrane, CNKI, and other databases to find randomized controlled studies on the efficacy of single-port laparoscopy and traditional laparoscopy for meta-analysis. The main outcomes of our study were the duration of surgery, the reduction of hemoglobin, and the cosmetic effect of the postoperative scar. The effect model was selected according to heterogeneity (random effect model or fixed effect model), and the relevant sensitivity analysis and publication bias test were performed.; Results: We searched a total of 501 related literature articles and finally included 19 studies involving 21 researchers. Comparison of single-port laparoscopic myomectomy with traditional surgery: Operation time had no significant difference (Standardized Mean Difference [SMD]: 0.13, 95% Confidence interval (CI), -0.04 to 0.30; I²=74%; P = 0.14); The reduction of hemoglobin is lower ([SMD]: -0.04; 95% CI, -0.23 to 0.14; I²=71%; P = 0.65), and the cosmetic effect of postoperative scar is more satisfactory ([SMD]: 0.42, 95% CI: 0.02 to 0.83; I²=72%, P= 0.04). There was no significant difference in conversion rate, postoperative pain, blood loss, postoperative gastrointestinal recovery time, or length of hospital stay.; Conclusion: Compared with traditional laparoscopy, the operation time of the treatment of uterine leiomyoma by single-port laparoscopy is not extended, the reduction of hemoglobin is less, and the cosmetic effect of the scar is better. Therefore, single-port laparoscopy is superior to traditional surgery in the treatment of uterine leiomyoma.; Systematic Review Registration: https://inplasy.com/inplasy-2023-3-0071/, identifier INPLASY202330071.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Li, Liu and Li.)

Li, Y., et al. (2020). "A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials." Experimental Gerontology 141: 111110.
	Background: Dehydroepiandrosterone (DHEA) has been aggressively sold as a dietary supplement to boost testosterone levels although the impact of DHEA supplementation on testosterone levels has not been fully established. Therefore, we performed a systematic review and meta-analysis of RCTs to investigate the effect of oral DHEA supplementation on testosterone levels.; Methods: A systematic literature search was performed in Scopus, Embase, Web of Science, and PubMed databases up to February 2020 for RCTs that investigated the effect of DHEA supplementation on testosterone levels. The estimated effect of the data was calculated using the weighted mean difference (WMD). Subgroup analysis was performed to identify the source of heterogeneity among studies.; Results: Overall results from 42 publications (comprising 55 arms) demonstrated that testosterone level was significantly increased after DHEA administration (WMD: 28.02 ng/dl, 95% CI: 21.44-34.60, p = 0.00). Subgroup analyses revealed that DHEA increased testosterone level in all subgroups, but the magnitude of increment was higher in females compared to men (WMD: 30.98 ng/dl vs. 21.36 ng/dl); DHEA dosage of ˃50 mg/d compared to ≤50 mg/d (WMD: 57.96 ng/dl vs. 19.43 ng/dl); intervention duration of ≤12 weeks compared to ˃12 weeks (WMD: 44.64 ng/dl vs. 19 ng/dl); healthy participants compared to postmenopausal women, pregnant women, non-healthy participants and androgen-deficient patients (WMD: 52.17 ng/dl vs. 25.04 ng/dl, 16.44 ng/dl and 16.47 ng/dl); and participants below 60 years old compared to above 60 years old (WMD: 31.42 ng/dl vs. 23.93 ng/dl).; Conclusion: DHEA supplementation is effective for increasing testosterone levels, although the magnitude varies among different subgroups. More study needed on pregnant women and miscarriage. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Li, Y., et al. (2023). "Effects of probiotics, prebiotics, and synbiotics on polycystic ovary syndrome: a systematic review and meta-analysis." Critical reviews in food science and nutrition 63(4): 522-538.
	This meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effects of probiotics, prebiotics, and synbiotics on insulin resistance (IR), lipid profiles, anthropometric indices, and C-reactive protein (CRP) level for polycystic ovary syndrome (PCOS). We searched 8 databases from their inception until 1st October, 2020. The effect sizes were expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Subgroup analyses were undertaken for further identification of effects of probiotics, prebiotics, and synbiotics, based on the following aspects: (1) type of intervention (probiotics, prebiotics, or synbiotics); (2) study duration (≥ 12 weeks or < 12 weeks); (3) number of probiotic strains (multi strains or single strain); (4) probiotic dose (≥ 2 × 10 8 colony-forming units [CFU] or < 2 × 10 8 CFU). A total of 17 eligible RCTs with 1049 participants were included. Results showed that probiotic, prebiotic, and synbiotic intake decreased fasting plasma glucose (SMD, -1.35; 95% CI, -2.22 to -0.49; p = 0.002), fasting insulin (SMD, -0.68; 95% CI, -1.08 to -0.27; p = 0.001), homeostatic model of assessment for IR (SMD, -0.73; 95% CI, -1.15 to -0.31; p = 0.001), triglycerides (SMD, -0.85; 95% CI, -1.59 to -0.11; p = 0.024), total cholesterol (SMD, -1.09; 95% CI, -1.98 to -0.21; p = 0.015), low-density lipoprotein cholesterol (SMD, -0.84; 95% CI, -1.64 to -0.03; p = 0.041), very-low-density lipoprotein cholesterol (SMD, -0.44; 95% CI, -0.70 to -0.18; p = 0.001), and increased quantitative insulin sensitivity check index (SMD, 2.00; 95% CI, - 0.79 to 3.22; p = 0.001). However, probiotic, prebiotic, and synbiotic supplements did not affect anthropometric indices, high-density lipoprotein cholesterol, and CRP levels. Subgroup analysis showed that probiotic or prebiotic might be the optimal choice for ameliorating IR or lipid profiles, respectively. Additionally, the effect was positively related to courses and therapeutical dose. Overall, the meta-analysis demonstrates that probiotic, prebiotic, or synbiotic administration is an effective and safe intervention for modifying IR and lipid profiles.

Li, Y., et al. (2021). "Efficacy and safety of traditional Chinese medicine on treating oligomenorrhea: a systematic review and meta-analysis." Annals of Palliative Medicine 10(12): 12955-12968.
	Background: Oligomenorrhea is one of the most frequent gynecologic complaints that interferes with women's life quality. Treatment using traditional Chinese medicine (TCM) is a preferred alternative therapy for oligomenorrhea. However, systematic reviews (SRs) evaluating the efficacy of TCM treatments for oligomenorrhea remain absent. The present SR and meta-analysis aimed to evaluate the efficacy and safety of TCM treatment for oligomenorrhea.; Methods: Randomized controlled trials (RCTs) published in English and Chinese were retrieved by searching in the databases in October 2019, including PubMed, Cochrane Library, EMBASE, Sinomed, CNKI, VIP, and WanFang databases. Quantitative analyses and quality assessments were then conducted based on abstracted data. This study protocol is registered PROSPERO, number CRD42018095660.; Results: A total of 26 eligible RCTs involving 2,389 patients were included in our analysis. Overall, we observed an effect of increasing menstrual blood volumes owing to using TCM treatments plus bio-medicine (BM) (n=649; MD, 12.05; 95% CI: 5.23 to 18.87; P<0.00001; I2=96%). Besides, TCM combined with BM yielded a significant prolongation in menstrual periods (MD, 1.20; 95% CI: 0.78 to 1.62; P<0.00001; I2=76%), and had potential improvements on enhancing effectiveness rates, increasing endometrial thickness, and raising the levels of estradiol (E2) and progesterone (P). Concerning adverse events (AEs), no significant difference was found in either group. The quality of evidence was relatively low.; Conclusions: This study seems to support the potential effect of TCM on treating oligomenorrhea. However, the relatively low quality of prior studies calls for future RCTs to further assess the efficacy of TCM on treating oligomenorrhea using rigorous designs.

Li, Y., et al. (2020). "Auricular therapy for polycystic ovary syndrome: A protocol for a systematic review and meta-analysis." Medicine 99(49): e23396.
	Background: This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of auricular therapy for patients with polycystic ovary syndrome (PCOS).; Methods: Randomized controlled trials of auricular therapy in treating PCOS will be searched in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, and Chinese Scientific Journal Database. The primary outcome is the body mass index. The study selection, data extraction, and study quality evaluation will be performed independently by 2 researchers. A meta-analysis will be performed using RevMan V5.3 statistical software if possible; otherwise, descriptive analysis or subgroup analysis will be conducted. The quality of evidence for outcomes will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.; Results: This study will evaluate the effect and safety of auricular therapy in treating PCOS.; Conclusions: The evidence we generated from the present study will provide more options for PCOS management in clinical practice.; The Registration Doi: 10.17605/OSF.IO/VBPSM.

Li, Y.-J., et al. (2019). "Effects of bariatric surgery on obese polycystic ovary syndrome: a systematic review and meta-analysis." Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 15(6): 942-950.
	Background: Bariatric surgery has been widely used for the treatment of obesity and its related metabolic diseases, such as type 2 diabetes (T2D), hypertension, and sleep apnea syndrome. Polycystic ovary syndrome (PCOS) is a common reproductive endocrine metabolic disease; however, little attention has been paid to the efficacy of bariatric surgery on PCOS.; Objective: To evaluate the efficacy of bariatric surgery on obese PCOS patients.; Setting: A systematic review and meta-analysis at a university hospital.; Methods: Online databases were searched for all studies reporting the efficacy of bariatric surgery for obese patients with PCOS up to October 2018.; Results: A total of 9 studies with 234 obese PCOS patients were included in this article. The results of meta-analysis showed that after bariatric surgery, there was a significant reduction of the incidence of abnormal menstruation (relative risk [RR] .23; 95% confidence interval [CI] .13-.43; P < .00001) and hirsutism (RR .47; 95% CI .28-.79; P = .004). Bariatric surgery can also cause a decrease in the serum total testosterone level (mean difference [MD] = -25.82; 95% CI -30.06 to -21.58; P < .00001), serum free testosterone level (MD = -4.10; 95% CI -6.97 to -1.23; P = .005), and body mass index (MD = -14.51; 95% CI -17.88 to -11.14; P < .00001). It also showed a significant effect on T2D (RR .09; 95% CI .03-.32; P = .0002) and hypertension (RR .21; 95% CI .05-.98; P = .05) in obese patients with PCOS.; Conclusions: Bariatric surgery can reduce the incidence of abnormal menstruation, improve hyperandrogenism and its clinical manifestations, and decrease the body mass index, prevalence of T2D, and hypertension in obese patients with PCOS. (Copyright © 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Li, Z., et al. (2020). "Effectiveness of cognitive behavioural therapy for perinatal depression: A systematic review and meta-analysis." Journal of Clinical Nursing 29(17-18): 3170-3182.
	AIMS AND OBJECTIVES: To systematically review the efficacy of cognitive behavioural therapy for improving mood in perinatal depression. BACKGROUND: The impact of cognitive behavioural therapy on perinatal depression has been evaluated in various studies, but there is uncertainty about their impact. DESIGN: Systematic review and meta-analysis. METHOD(S): Nine electronic literature databases were searched to retrieve eligible randomised controlled trials: CNKI, VIP digital database, Chinese Wanfang database, the Cochrane library, PubMed, Web of science, EMBASE, PsycINFO, CINAHL from the inception of the databases up to 15 November 2019. The eligible studies were screened and extracted, and then, the methodological quality was evaluated independently by two researchers. The meta-analyst software (Rev Man 5.3) was used to conduct the meta-analysis. Checklist of Preferred Reporting Items for Systematic Reviews and Meta-analyses has been followed. RESULT(S): Thirteen RCTs with 966 participants were included. The results showed that the CBT group was superior to the usual care group in reducing depression symptoms of pregnant women after treatment immediately, and the difference was statistically significant. Similarly, at postpartum (<4 months), the results showed that the CBT group was superior to the usual care group in improving depression symptoms of pregnant women. However, there was no statistical difference at postpartum (>4 months). CONCLUSION(S): Cognitive behavioural therapy can effectively relieve the symptoms of depression at short-term effect. However, its long-term effect need to be verified by further clinical studies. RELEVANCE TO CLINICAL PRACTICE: This meta-analysis suggested that cognitive behavioural therapy should be considered as a complementary programme for patients with perinatal depression. Medical workers could apply cognitive behavioural therapy into daily routine cares for perinatal depression.Copyright © 2020 John Wiley & Sons Ltd.

Li, Z., et al. (2022). "A systematic review on quality of life (QoL) of patients with peritoneal metastasis (PM) who underwent pressurized intraperitoneal aerosol chemotherapy (PIPAC)." Pleura and Peritoneum 7(2): 39-49.
	Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM). Quality of life (QoL) has increasingly been used as an endpoint to evaluate treatment outcomes. This review aims to identify evidence on how PIPAC would impact the QoL of PM patients.; Content: A systematic review was performed on articles identified from Medline, EMBASE, PsycInfo, and Web of Sciences. A meta-analysis was conducted on further selected studies. ACROBAT-NRSI was attempted to assess the risk of bias (RoB).; Summary: Nine studies using the EORTC QLQ-C30 questionnaire to assess QoL after repeated PIPAC cycles were identified. Majority was found to be moderately biased and a great extent of heterogeneity was observed. Four studies on PM from either gastric cancer (GC) or epithelial ovarian cancer (EOC) were included for meta-analysis. In 31 GC patients and 104 EOC patients, QoL remained stable in 13/14 and 11/14 EORTC QLQ-C30 scales. PIPAC was inferior to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in global QoL and functioning but superior in symptom reduction.; Outlook: PIPAC is a well-tolerated option for most GC and EOC patients with irresectable PM. Future trials are warranted to confirm the findings.; Competing Interests: Competing interests: Authors state no conflict of interest. (© 2022 Zhenyue Li et al., published by De Gruyter, Berlin/Boston.)

Li, Z., et al. (2023). "Acupuncture combined with Chinese herbal medicine in the treatment of perimenopausal insomnia: A systematic review and meta-analysis." Medicine 102(45): e35942.
	Background: Perimenopausal insomnia (PMI) is a relatively common menopausal symptom that can cause serious problems for the women themselves and their families. Today, the world is facing the trend and challenges of an aging population. It is reported that about 1.5 million women worldwide enter menopause every year, with sleep disorder identified as a core symptom. The efficacy of acupuncture combined with traditional Chinese medicine for treating PMI has been recognized by patients and doctors.; Methods: We searched 8 databases to identify 15 randomized controlled trials evaluating the effects of acupuncture combined with traditional Chinese medicine on sleep in patients with PMI compared with Western medicine alone. Subsequently, data extraction and analysis were performed to assess the quality and risk of bias of the study method design, and a meta-analysis of the data was performed.; Results: This study included 15 randomized controlled trials involving 1188 patients with PMI. The results show that acupuncture combined with traditional Chinese medicine seems to be more effective than Western medicine in the treatment of PMI: efficiency (RR: 1.18; 95% CI: 1.08, 1.29; P = .001); the Pittsburgh Sleep Quality Index (PSQI) (WMD: -2.77; 95% CI: 4.15-1.39; P < .0001); follicle-stimulating hormone (FSH) (WMD: -31.45; 95% CI: 42.7-20.2; P < .001) and the Hamilton Anxiety Score (HAMA) (WMD: -2.62, 95% CI: -3.93, -1.32; P < .0001). Compared with western medicine, E2 (WMD: 5.07; 95% CI: 5.78-15.92; P = .36) and LH (WMD: -4.86; 95% CI: 11.5-1.78; P = .151) had no difference.; Conclusion: The current analysis results show that acupuncture combined with Chinese medicine seems to have a more positive effect than western medicine alone in improving sleep and FSHF in PMI patients, but no difference has been found in improving E2 and LH. This study provides a basis for acupuncture combined with Chinese medicine to treat PMI. However, due to the higher risk of evaluation in included studies, more rigorous randomized controlled trials and higher quality studies are needed to validate included studies.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lialy Hagar, E., et al. (2023). "Effects of different physiotherapy modalities on insomnia and depression in perimenopausal, menopausal, and post-menopausal women: a systematic review." BMC Women's Health 23(1): 363.
	Background: Menopause is the time that marks passing 12 months after the last menstruation cycle in women between ages 40-50. Menopausal women often experience depression and insomnia that significantly impact their overall well-being and quality of life. This systematic review aims to determine the effects of different therapeutic physiotherapy modalities on insomnia and depression in perimenopausal, menopausal, and post-menopausal women.; Methodology: After identifying our inclusion/exclusion criteria, we conducted a database search in Ovid Embase, MIDRIS, PubMed, Cochrane, and ScienceOpen, where 4007 papers were identified. By using EndNote software, we excluded duplicates, unrelated, and non-full text papers. Adding more studies from manual search, we finally included 31 papers including 7 physiotherapy modalities: exercise, reflexology, footbath, walking, therapeutic and aromatherapy massage, craniofacial message, and yoga.; Results: Reflexology, yoga, walking and aromatherapy massage showed an overall significant impact on decreasing insomnia and depression in menopausal women. Most of exercise and stretching interventions also showed improvement in sleep quality but inconsistent findings regarding depression. However, insufficient evidence was found regarding the effect of craniofacial massage, footbath, and acupressure on improving sleep quality and depression in menopausal women.; Conclusion: Using non-pharmaceutical interventions such as therapeutic and manual physiotherapy have an overall positive impact on reducing insomnia and depression in menopausal women. (© 2023. The Author(s).)

Lian, P. H., et al. (2020). "Intraoperative Vaginal Perforation During Various Mid-Urethral Sling Procedures Treating Female Stress Urinary Incontinence." Journal of Investigative Surgery 33(3): 203-210.
	Background: Incidence of intraoperative vaginal perforation is generally considered to be low but varies among different procedures. Vaginal perforation could not only prolong the surgeries and aggravate surgical trauma but also result in postoperative discomfort or even a second surgery. Method(s): Vaginal perforation, vaginal epithelial perforation, vaginal wall perforation, vaginal penetration, urinary incontinence were searched in PubMed, Cochrane, Embase database to identify the qualified clinical trial and relevant literature sources were also searched. Result(s): A total of 9223 cases of from 33 trials from literatures and 387 cases from our own trail were analyzed, which provided detailed data on intraoperative vaginal perforation. Incidence of intraoperative vaginal perforation during mid-urethral sling surgery treating stress urinary incontinence was generally low, which was 1.56%. Incidence of intraoperative vaginal perforation during transobturator (TOR) procedure was higher than that during retropubic (RPR) procedure, which were 2.11% and 0.89% respectively. Incidence of intraoperative vaginal perforation during outside-to-inside TOR procedure like TOT and MONARC was higher than that during inside-to-outside TOR procedure like TVT-O, which were 2.74% and 1.52%, respectively. Incidence of intraoperative vaginal perforation during single-incision surgery like H-type TVT-SECUR reached 1.97%, while no report on U-type TVT-SECUR surgeries. Conclusion(s): The incidence of intraoperative vaginal during mid-urethral sling procedures for female stress urinary incontinence is fairly high. Vaginal perforation was more common in trans-obturator route (TOR) than retropubic route (RPR). In TOR route, it was less frequent in inside-to-outside procedure than outside-to-inside procedure. Surgery proficiency could also have an impact on this complication.Copyright © 2018, © 2018 Taylor & Francis Group, LLC.

Liang Angela, L., et al. (2022). "Medical Cannabis for Gynecologic Pain Conditions: A Systematic Review." Obstetrics and Gynecology 139(2): 287-296.
	Objective: The endocannabinoid system is involved in pain perception and inflammation. Cannabis contains delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are cannabinoids that bind to endocannabinoid system receptors. A fatty acid amide called palmitoylethanolamide (PEA) enhances endogenous cannabinoids. Given that use of medical cannabis is increasing, we sought to characterize patterns of cannabis use for gynecologic pain and its effectiveness as an analgesic.; Data Sources: We searched PubMed, EMBASE, Scopus, Cochrane, and ClinicalTrials.gov using terms for "woman," "cannabis," and "pain" or "pelvic pain" or "endometriosis" or "bladder pain" or "cancer." The search was restricted to English-language articles published between January 1990 and April 2021 and excluded animal studies.; Methods of Study Selection: The initial search yielded 5,189 articles with 3,822 unique citations. Studies were included if they evaluated nonpregnant adult women who used cannabinoids for gynecologic pain conditions (eg, chronic pelvic pain, vulvodynia, endometriosis, interstitial cystitis, malignancy). Study types included were randomized controlled trials (RCTs), cohort studies, and cross-sectional studies. Covidence systematic review software was used.; Tabulation, Integration, and Results: Fifty-nine studies were considered for full review, and 16 met inclusion criteria. Prevalence of cannabis use ranged from 13% to 27%. Most women ingested or inhaled cannabis and used cannabis multiple times per week, with dosages of THC and CBD up to 70 mg and 2,000 mg, respectively. Sixty-one to 95.5% reported pain relief. All six prospective cohort studies and one RCT of PEA-combination medications reported significant pain relief, and the average decrease in pain after 3 months of treatment was 3.35±1.39 on the 10-point visual analog scale. However, one fatty acid amide enzyme inhibitor RCT did not show pain reduction.; Conclusion: Survey data showed that most women reported that cannabis improved pain from numerous gynecologic conditions. Cohort studies and an RCT using PEA-combination medications reported pain reduction. However, interpretation of the studies is limited due to varying cannabis formulations, delivery methods, and dosages that preclude a definitive statement about cannabis for gynecologic pain relief.; Systematic Review Registration: PROSPERO, CRD42021248057.; Competing Interests: Financial Disclosure Jenell S. Coleman holds investments in a cannabis exchange-traded fund. The other authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Liang, J., et al. (2021). "The role of estrogen deprivation therapy in premenopausal women with primary unresectable intracardiac leiomyomatosis: a systematic review and meta-analysis." Orphanet journal of rare diseases 16(1): 453.
	Background: Intracardiac leiomyomatosis (ICLM) is a rare life-threatening form of intravenous leiomyomatosis (IVLM). The incomplete resection and recurrence are associated with high morbidity and mortality. The objective of this study is to identify that whether estrogen deprivation therapies, including bilateral salpingo-oophorectomy (BSO)-based surgery and gonadotrophin releasing hormone agonists (GnRHa) administration, could bring benefits to patients with primary unresectable ICLM.; Methods: PubMed/MEDLINE (Ovid) was searched (up to May 2021) for studies reporting individual patient data on demographics, clinicopathological features, treatment, and follow-up information. Exclusion criteria were patients who may have been included in two or more publications. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.; Results: A total of 114 patients from 70 papers were included. Several reports showed that the tumor in the right atrium and inferior vena cava shrank dramatically after BSO-based surgery, or GnRHa administrated preoperatively in premenopausal women. The rate of complete resection was 64.04% in patients with ICLM, which was 85.25% in no/slight adhesion and no pulmonary nodules group, while 22.22% in firm/extensive adhesion and/or pulmonary nodules group (p < 0.0001). Meanwhile, the recurrence rates in patients with complete resection and incomplete resection were 4.29% and 37.84% respectively (p < 0.0001). Furthermore, complete resection with BSO had the lowest recurrence rate of 3.13%, incomplete resection with BSO had a progression rate of 45.45%, while incomplete resection with ovarian preservation had the highest progression rate of 75.00%.; Conclusions: The recurrence rate of ICLM was closely related to firm/extensive adhesion in IVC or above, and/or pulmonary nodules. BSO-based surgery might reduce the recurrence rate no matter ICLM could be completely resected or not. In addition, estrogen deprivation therapies could decrease tumor burden as a primary treatment, and further make a secondary complete resection feasible in premenopausal women with initially unresectable ICLM. (© 2021. The Author(s).)

Liang, X. Y., et al. (2023). "Effectiveness and safety of the combination of Chinese herbal medicine and acupuncture for women with polycystic ovarian syndrome: A systematic review and meta-analysis of randomized controlled trials." European journal of integrative medicine 63: 102291.
	Introduction: This systematic review aimed to evaluate the effectiveness and safety of Chinese herbal medicine (CHM) plus acupuncture for women with polycystic ovarian syndrome (PCOS). Method(s): We searched for eligible randomized controlled trials (RCTs) in nine Chinese and English databases from their inception to May 7, 2023. The Cochrane "Risk of bias" tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods were used to assess the methodological quality and the certainty of the evidence. Effectiveness is presented as the risk ratio (RR) or mean difference with 95% confidence interval (CI). Result(s): A total of 52 studies were included in this systematic review (n = 4180 participants). The overall quality of the RCTs was reduced by unclear or high risk of bias. The certainty of the evidence ranged from very low certainty to moderate certainty. None of the included studies reported the live birth rate. Among women with PCOS seeking fertility treatment, both CHM and acupuncture had a beneficial effect on the clinical pregnancy rate (CHM plus acupuncture (Intervention A), 9 RCTs, n = 754 participants, RR 1.28, 95% CI 1.10, 1.49; moderate certainty evidence; CHM plus acupuncture plus CMT (Intervention B), 16 RCTs, n = 1269 participants, RR 1.71, 95% CI 1.50, 1.94; moderate certainty evidence) and ovulation rate (Intervention A, 5 RCTs, n = 395 participants, RR 1.31, 95% CI 1.15, 1.49; low certainty evidence; Intervention B, 7 RCTs, n = 729 participants, RR 1.31, 95% CI 1.16, 1.48; low certainty evidence) compared to the control group. Conclusion(s): There is currently very low to moderate certainty evidence that CHM plus acupuncture can improve the fertility and clinical symptoms of PCOS patients. Further rigorous, double-blinded, placebo-controlled trials are needed to determine the effectiveness of complex interventions of CHM plus acupuncture for treating PCOS.Copyright © 2023

Liang, Z., et al. (2023). "A systematic review and meta-analysis: clinical outcomes of recurrent pregnancy failure resulting from preimplantation genetic testing for aneuploidy." Frontiers in Endocrinology 14: 1178294.
	Background: Preimplantation genetic testing for aneuploidy (PGT-A) is an emerging technology that aims to identify euploid embryos for transfer, reducing the risk of embryonic chromosomal abnormalities. However, the clinical benefits of PGT-A in recurrent pregnancy failure (RPF) patients, particularly in young RPF patients, remains uncertain.; Objective and Rationale: This meta-analysis aimed to determine whether RPF patients undergoing PGT-A had better clinical outcomes compared to those not undergoing PGT-A, thus assessing the value of PGT-A in clinical practice.; Search Methods: We systematically searched PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database for Chinese Technical Periodicals (VIP) from 2002 to 2022. Thirteen published studies involving 930 RPF patients screened using PGT-A and over 1,434 RPF patients screened without PGT-A were included in this meta-analysis. Clinical outcomes were evaluated based on embryo transfers after PGT-A (n=1,015) and without PGT-A (n=1,799).; Clinical Outcomes: The PGT-A group demonstrated superior clinical outcomes compared to the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) group. The PGT-A group had a significantly higher implantation rate (IR) (RR=2.01, 95% CI: [1.73; 2.34]), clinical pregnancy rate (CPR) (RR=1.53, 95% CI: [1.36; 1.71]), ongoing pregnancy rate (OPR) (RR=1.76, 95% CI: [1.35; 2.29]), live birth rate (LBR) (RR=1.75, 95% CI: [1.51; 2.03]), and significantly lower clinical miscarriage rate (CMR) (RR=0.74, 95% CI: [0.54; 0.99]). Subgroup analysis based on patient age (under 35 years and 35 years or older) showed that both PGT-A subgroups had significantly better CPR (P<0.01) and LBR (P<0.05) values compared to the IVF/ICSI groups.; Summary: This meta-analysis demonstrates that PGT-A in RPF patients, is associated with improved clinical outcomes, including higher IR, CPR, OPR, and LBR values, and lower CMR compared to the IVF/ICSI group. These findings support the positive clinical application of PGT-A in RPF patients.; Systematic Review Registration: http://INPLASY.com, identifier INPLASY 202320118.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Liang, Wen, Li, Zeng and Huang.)

Liao, B., et al. (2019). "[Extracorporeal shock wave therapy for chronic prostatitis / chronic pelvic pain syndrome: A meta-analysis]." Zhonghua nan ke xue = National journal of andrology 25(10): 914-922.
	Objective: To systematically evaluate the clinical efficacy of the extracorporeal shock wave therapy (ESWT) in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) and provide some evidence for the management of the disease.; Methods: We searched the PubMed, Cochrane Library, EMbase, CNKI, VIP, WanFang Data and CBM databases on the internet, as well as the Journal of Clinical Urology and Chinese Journal of Urology manually for randomized controlled trials (RCT) on the treatment of CP/CPPS by ESWT published from their establishment till February 1, 2019. Two reviewers independently screened the literature, extracted the data and assessed the risk of bias of the included studies, followed by a meta-analysis with the RevMan 5.3 software.; Results: Totally 12 RCTs involving 838 CP/CPPS patients were included in this study. Compared with the controls, the patients treated by ESWT showed a significantly higher rate of overall effectiveness (OR = 8.75, 95% CI: 5.16 to 14.86, P < 0.000 01) and lower NIH-CPSI scores (MD = －5.10, 95% CI: －6.13 to －4.06, P < 0.000 01). Subgroup analyses manifested that a higher number of shock wave pulses (≥2 000) had a better therapeutic effect (MD = －4.99, 95% CI: －6.20 to －3.38, P < 0.000 01 in the >2 000-pulse group; MD = －5.76, 95% CI: －7.09 to －4.42, P < 0.000 01 in the 2 000-pulse group).; Conclusions: ESWT can raise the rate of overall clinical effectiveness and improve the symptoms of chronic prostatitis in the treatment of CP/CPPS. This conclusion, however, is to be further supported by more RCTs with higher quality, larger sample size and better design.

Liao, D., et al. (2022). "Clinical evidence of the effects of carnitine supplementation on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: a systematic review and meta-analysis." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(2): 110-115.
	Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Several clinical trials have investigated the influence of carnitine on metabolic variables in PCOS, but have yielded conflicting results. This study aimed to summarize the clinical evidence of the effects of carnitine on weight management, glycemic and serum lipids controls in women with PCOS by conducting a meta-analysis of randomized control trials (RCTs). PubMed, Embase, Web of Sciences, Scopus, and the CENTRAL database were searched from inception to March 2021 for eligible articles. Study selection and assessment of quality were conducted independently by two investigators. Effect sizes for each outcome were reported with the weighted mean differences (WMDs) and 95% confidence intervals (CIs). The statistical heterogeneity of the included clinical trials was tested using the I 2 statistic. Six studies with 672 PCOS participants were included for meta-analysis. Our results revealed that carnitine supplements significantly decreased total cholesterol, low-density lipoprotein-cholesterol, triglycerides, body weight, body mass index, hip circumference, and waist circumference (All p < .05). In addition, carnitine intervention also improved the levels of high-density lipoprotein cholesterol. However, no significant changes were seen in glucose homeostasis parameters. These results were stable after sensitivity analysis, and no significant publication biases were detected. Based on current evidence, carnitine supplementation in women with PCOS had beneficial effects on weight loss and lipid profiles. Further large-scale, well-designed RCTs are required to confirm these results.

Liao, J. B., et al. (2021). "Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates." Journal for Immunotherapy of Cancer 9(9).
	BACKGROUND: Anti-programmed death 1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies have shown modest activity as monotherapy in recurrent ovarian cancer. Platinum chemotherapies induce T-cell proliferation and enhance tumor recognition. We assessed activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer. PATIENTS AND METHODS: This phase I/II, single-arm clinical trial studied concurrent carboplatin and pembrolizumab in recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer. Primary platinum refractory patients were excluded. Patients were treated after progression on subsequent non-platinum systemic therapy after becoming platinum resistant or refractory. Pembrolizumab 200 mg was given on day 1 and carboplatin area under the curve 2 on days 8 and 15 of a 3-week cycle until progression. Imaging was assessed by blinded independent review. PD-L1 expression was assessed by immunohistochemistry. Flow cytometry on peripheral blood mononuclear cells was performed for CD3, CD4, CD8, PD1, CTLA4 and Ki67. RESULTS: The most common treatment-related adverse events were lymphopenia (18%) and anemia (9%) with most being grade 1 or 2 (93%). Of 29 patients treated, 23 patients were evaluable for best objective response: 10.3% (95% CI 2.2 to 27.4) had partial response (PR), 51.7% (95% CI 32.5 to 70.6) had stable disease (SD). 56.5% of patients had decreases in target lesions from baseline. All PD-L1-positive patients achieved PR (3/7, 42.8%) or SD (4/7, 57.2%). Median progression-free survival was 4.63 months (95% CI 4.3 to 4.96). Median OS was 11.3 months (95% CI 6.094 to 16.506). Peripheral CD8+PD1+Ki67+ T cells expanded after 3 (p=0.0015) and 5 (p=0.0023) cycles. CTLA4+PD1+CD8+ T cells decreased through the course of treatment up to the 12th cycle (p=0.004). When stratified by ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden at baseline, patients with a ratio ≥0.0375 who had a significantly longer median OS of 18.37 months compared with those with a ratio <0.0375 who had a median OS of 8.72 months (p=0.0099). No survival advantage was seen with stratification by tumor burden alone (p=0.24) or by CD8+PD1+Ki67+ T cells alone (p=0.53). CONCLUSIONS: Pembrolizumab with carboplatin was well-tolerated and active in recurrent platinum-resistant ovarian cancer. A ratio of peripheral T-cell exhaustion to radiographic tumor burden may identify patients more likely to benefit from this chemoimmunotherapy. TRIAL REGISTRATION NUMBER: NCT03029598.

Liao, L., et al. (2022). "Sacral Neuromodulation Using a Novel Device with a Six-contact-point Electrode for the Treatment of Patients with Refractory Overactive Bladder: a Multicenter, Randomized, Single-blind, Parallel-control Clinical Trial." European Urology Focus 8(6): 1823‐1830.
	BACKGROUND: A novel sacral neuromodulation system (SacralStim) which has an electrode with six contact points was recently designed. OBJECTIVE: To evaluate the effectiveness and safety of the SacralStim system for treating patients with refractory overactive bladder (OAB). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, randomized, single‐blind clinical trial. Patients with refractory OAB were enrolled from January 2018 to May 2020. INTERVENTION: Participants were randomly allocated to the treatment group (SNM on) or the control group (SNM off) for a single‐blind period of 12 ± 2 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the percentage of patients with a reduction in the average number of voids/24 h of at least 50% at the 12‐wk follow‐up visit. Other follow‐up evaluations, including voiding diary outcomes, questionnaires on Overactive Bladder Symptom Score (OABSS), quality of life (QoL), device satisfaction, and causes of adverse events (AEs), were performed over the first 48 wk after implantation. RESULTS AND LIMITATIONS: The therapeutic success rate at 12 wk was 56.76% in the treatment group and 11.11% in the control group (p < 0.001). There were significant differences in voiding diary variables between the two groups, including changes in the average number of voids/24 h, micturition volume/void, and improvement in the urge incontinence ratio. No severe AEs occurred. A limitation is the sham stimulation used as a control in the study. A head‐to‐head study is required to make a direct comparison of devices with six and four contact points. CONCLUSIONS: This clinical trial provides strong evidence that patients with refractory OAB benefit from the novel SacralStim system. More research is required for direct comparison of the SacralStim system with traditional four‐contact‐point devices. PATIENT SUMMARY: This study confirms the effectiveness and safety of a novel SacralStim system that stimulates the sacral nerve for treatment of overactive bladder. The system has an electrode with six contact points and can provide more programming options after implantation.

Liao, M., et al. (2024). "Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial." Endocrine 83(1): 227-241.
	Purpose: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS. Method(s): In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-mug ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA. Result(s): Eighty(80%) patients completed the study. Both interventions improved menstrual cycle, polycystic ovaries, LH(luteinizing hormone) and HbA1c(hemoglobin A1c) levels after the 12-week treatment. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI (Body Mass Index), and waist circumference, FBG(fasting blood glucose), AUCI(area under curve of insulin),TC (Total Cholesterol), IL-6(Interleukin-6) and improving insulin sensitivity, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in improving hyperandrogenemia, including T(total testosterone), LH, LH/FSH(Luteinizing hormone/follicle-stimulating hormone), SHBG(sex hormone-binding globulin) and FAI (free androgen index). By contract, GLP-1RA+Met group only improved LH. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9). Conclusion(s): Both CPA/EE+Met and GLP-1RA + Met treatment improved reproductive functions in overweight PCOS women. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI, and waist, and improving metabolism, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in reducing hyperandrogenemia. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment. Trial registration ClinicalTials.gov Trial No:: NCT03151005. Registered 12 May, 2017, https://clinicaltrials.gov/ct2/show/NCT03151005 .Copyright © 2023, The Author(s).

Lichen, Y., et al. (2023). "Acupuncture for relieving pain in pelvic inflammatory disease: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Lidia, M., et al. (2023). "The infracolic-omentectomy for early stage (FIGO I-II) in borderline ovarian tumors, it is necessary?: A Systematic Review and Meta-analysisA protocol for Systematic Review and Meta-analysis."
	
Lietz, A., et al. (2023). "Quality of life in women with chronic recurrent vulvovaginal candidosis: A sub-analysis of the prospective multicentre phase IIb/III Prof-001 study." Mycoses 66(9): 767-773.
	Background: Chronic recurrent vulvovaginal candidosis (RVVC), defined as three or more episodes of vulvovaginal candidosis per year, significantly impairs quality of life (QoL) and sexual health.; Objectives: The primary objective of this study was to assess health-related QoL in women with RVVC using validated questionnaires before and after treatment. The secondary objective was to analyse the effect of RVVC on women's sexual health.; Patients/methods: This was a sub-analysis of a randomised, controlled, double-blinded study titled 'A phase IIb/III, parallel-arm, randomized, active-controlled, double-blind, double-dummy, multicenter, non-inferiority study in patients with recurrent vulvovaginal candidosis to compare the clinical efficacy, safety and tolerability of topically administered ProF-001 (Candiplus®) to oral fluconazole, which was conducted at 35 study sites in Austria, Poland and Slovakia. QoL was assessed using the European Quality of Life (EQ) five-dimension five-level scale (EQ-5D-5L) and visual analogue scale (EQ-VAS) questionnaires, followed by specific questions regarding sexuality.; Results: From 2019 to 2021, 360 of 432 (83.3%) women with RVVC had accomplished a 6-months maintenance treatment and were enrolled in this sub-analysis. The EQ-5D-5L and EQ-VAS scores demonstrated improved QoL in 137 (65.2%) and 159 (75.4%) women after 6 months of maintenance treatment. Each individual aspect of sexual health significantly improved (all p < .05). A reduction in pain frequency during or after sexual intercourse in the 6-month period occurred in 124 (66.3%) women.; Conclusions: Women with RVVC had high QoL and sexual health impairment; however, a 6-months maintenance treatment resulted in effective improvement in QoL and sexual health. (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)

Lijuan, D., et al. (2022). "Effectiveness of redcore lotion in patients with vulvovaginal candidiasis: a systematic review and Meta-analysis." Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 42(4): 487-492.
	Objective: To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of randomized controlled trials.; Methods: A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019. Randomized controlled trials in the treatment for VVC were included; only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included. Relative risk (RR) and 95% confidence intervals (CI) were used in the Meta-analysis.; Results: Seven studies involving 768 patients suffering from VVC were identified; 468 of the patients were pregnant women (60.9%). Combination group (Redcore lotion plus miconazole) was more effective in reduCIng symptomatic episodes of VVC than miconazole alone, with respect to cure rate (RR, 1.31; 95% CI, 1.09-1.57; P = 0.01), fungal culture negative rate (RR, 1.21; 95% CI, 1.04-1.41; P = 0.01), and effective rate (RR, 1.18; 95% CI, 1.05-1.35; P = 0.01). Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate (RR, 1.48; 95% CI, 1.16-1.88, P < 0.01), fungal culture negative rate (RR, 1.26; 95% CI; 1.09-1.47; P < 0.01), and effective rate (RR, 1.25; 95% CI, 1.10-1.42; P < 0.01). Additionally, the observed risk of adverse events was lower in the combination medication group (RR, 0.30; 95% CI, 0.14-0.65; P < 0.01).; Conclusions: Though overall quality of individual studies was low, Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.

Lim, H., et al. (2021). "Preservation of the ovarian reserve and hemostasis during laparoscopic ovarian cystectomy by a hemostatic agent versus suturing for patients with ovarian endometriosis: study protocol for randomized controlled, non-inferiority trial (PRAHA-2 trial)." ResearchSquare.
	Background: Endometriosis (EMS) can be implanted everywhere, especially in pelvic organs. EMS can be asymptomatic, but it can result in pelvic pain and infertility by inducing local inflammation and pelvic adhesion. The prevalence of EMS is about 10% in reproductive-age women and higher in women with pelvic pain or infertility. For young patients with ovarian EMS, laparoscopic ovarian cystectomy is effective in relieving pelvic pain and preventing local recurrence. However, there is a concern that the ovarian reserve would decrease after the operation because of removal of a part of the normal ovarian tissue and thermal damage during hemostasis, which depends on types of hemostasis such as bipolar electrocoagulation, suturing, and the use of a hemostatic agent. In this study, we aim to evaluate the protective effect for the ovarian reserve and hemostasis between a hemostatic agent and suturing during laparoscopic ovarian cystectomy for patients with ovarian EMS. Methods: This study is a randomized controlled, non-inferiority trial, where a total of 90 patients with ovarian EMS will be randomly assigned to the experimental (hemostatic agent) and control (suturing) groups. In the control group, a barbed suture will be applied for hemostasis, whereas a hemostatic agent will be applied in the experimental group. If two methods are insufficient, bipolar electrocoagulation will be applied for complete hemostasis. As the primary endpoint, the reduction rate of serum anti- Müllerian hormone (AMH) levels reflecting the ovarian reserve will be compared between the two groups 12 weeks after surgery. As secondary endpoints, we will compare the reduction rate of AMH level 48 weeks after surgery, the time required to complete hemostasis, the success rate of hemostasis within 10 minutes, and adverse events associated with operation. Discussion: We expect that the protective effect for the ovarian reserve and hemostasis may be comparable between the two methods, suggesting that a hemostatic agent may be preferred considering that it is easy to use during laparoscopic ovarian cystectomy. Trial registration: ClinicalTrials.gov: NCT04643106. Registered on 22 November 2020.

Lim, J., et al. (2023). "Intravenous Iron Therapy to Treat Anemia in Oncology: A Mapping Review of Randomized Controlled Trials." Current Oncology 30(9): 7836-7851.
	Anemia is a common problem when patients present with cancer, and it can worsen during treatment. Anemia can directly impact the cognitive and physical quality of life and may impair fitness for oncological therapy. The most common cause of anemia is iron deficiency. Newer intravenous (IV) iron formulations offer a safe and rapidly effective treatment option. We performed a systematic mapping review of randomized controlled trials (RCTs) evaluating intravenous iron therapy in patients with cancer and anemia and their outcomes. A total of 23 RCTs were identified. The median number of patients enrolled was 104 (IQR: 60-134). A total of 5 were focused on surgical outcomes (4 preoperative, 1 postoperative), and 15 were in adjuvant therapies for a variety of tumor types (breast, colorectal, lung, gynecological, myeloid, and lymphomas), 10 of which were in combination with erythropoietin-stimulating agents (ESAs) therapy, 2 in radiotherapy, and 1 in palliative care. Overall, the studies reported that the use of IV iron increased hemoglobin concentration and decreased transfusion rates during different cancer treatment regimes. IV iron can be administered safely throughout the cancer treatment pathway from primary surgery to the palliative setting. More studies are needed to demonstrate net clinical outcomes.Copyright © 2023 by the authors.

Lim, J., et al. (2019). "Evaluation for effectiveness of oriental medicinebased infertility treatment and spontaneous pregnancy rate of infertile patients using systematic review." Journal of the Korean Medical Association 62(12): 645-652.
	This study is to evaluate the effectiveness of oriental medicine-based infertility treatment and to examine the validity of the oriental medicine-based infertility treatment program through a systematic review. The literature search database included not only PubMed, DBpia, and RISS (Research Information Sharing Service) but also OASIS (Oriental Medicine Advanced Searching Integrated System) and Korean Traditional Knowledge Portal. Among 575 articles that searched, only three papers were randomized controlled trials and could be included for the evaluation of the effects of oriental medicine-based infertility treatment. There was no study showing the effectiveness of oriental medicine-based infertility treatment alone. Among 5,165 articles that searched, only 15 studies could be included for the evaluation of the natural pregnancy rate of infertile patients. These studies reported the natural pregnancy rates from 20.3% to 41.9%. As pregnancy rates ranged from 23.8% to 27.6% after the oriental medicine-based infertility treatment supporting programs, we cannot conclude that pregnancy rates for infertile patients might increase by this project. Therefore, there is a need to reconsider whether the oriental medicine-based infertility treatment program should continue in the future.Copyright © Korean Medical Association.

Lim, K. H. (2024). "Effects of Integrated Music-Video Therapy on Pain and Anxiety During High-Dose-Rate Brachytherapy." Pain management nursing : official journal of the American Society of Pain Management Nurses.
	PURPOSE: This study aimed to examine the effect of integrated music-video therapy on pain and anxiety of gynecologic cancer patients at different stages of brachytherapy. DESIGN: This study used a single-group crossover design. METHOD(S): Data on 27 patients diagnosed with gynecologic cancer and receiving brachytherapy were collected from February 2018 to January 2019. Participants' pain and anxiety levels were measured four times using a numerical rating scale (before, during, after applicator insertion, and during the radiation). In addition, vital signs were measured three times (before, after applicator insertion, and during radiation). Data were analyzed for frequency and percentage. The normality and homogeneity of the dependent variables were tested using the Kolmogorov-Smirnov and Mann-Whitney U tests, respectively. RESULT(S): Significant differences were found between the experimental and control phases in pain degree during radiation exposure (Z = -1.68, p = .046) and anxiety degree during applicator insertion (Z=-4.42, p = .000), after applicator insertion (Z = -4.85, p = .000), and during radiation exposure (Z = -5.38, p = .000). However, no significant difference was found between the changes in blood pressure, pulse, and respiration at any time point. CONCLUSION(S): The findings suggest the need to actively employ integrated music-video therapy to reduce acute pain and anxiety in gynecologic cancer patients undergoing brachytherapy. CLINICAL IMPLICATIONS: This study provides insights into the methodological approaches for implementing integrated music-video therapy in clinical practice, targeting the reduction of acute pain and anxiety triggered by gynecological surgeries and procedures.Copyright © 2024. Published by Elsevier Inc.

Lim, M. C., et al. (2023). "325TiP A phase III randomized controlled trial in primary stage three and four ovarian cancer after interval cytoreductive surgery (FOCUS/KOV-HIPEC-04)." Annals of Oncology 34(Supplement 4): S1597.
	Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery increases progression-free and overall survival for patients with advanced-stage epithelial ovarian cancer in two randomised controlled trials (OV-HIPEC-01 and KOV-HIPEC-01). The aim of this trial is to identify the survival benefit of HIPEC in advanced ovarian cancer in the era of maintenance therapy of bevacizumab and/or PARP inhibitor. Trial design: The KOV-HIPEC-04 is a multicenter, 1:1 randomised, phase III trial that will enroll 520 patients with primary epithelial ovarian cancer who completed neoadjuvant chemotherapy. Patients will be randomised at the time of interval cytoreductive surgery with achieving complete cytoreduction or cytoreduction with no more than 2.5mm of residual disease to receive HIPEC (experimental arm, 41.0-42.0degreeC cisplatin 75mg/m2, 90 minutes) or not (control arm). After recovery from surgery, patients will receive postoperative platinum-based adjuvant chemotherapy followed by maintenance therapy with PARP inhibitor or bevacizumab. The primary endpoint is to evaluate overall survival (OS); secondary objectives are progression-free survival (PFS), cancer-specific survival, time to first subsequent therapy, safety, and quality of life. Assuming that the enrollment period is five years and the follow-up period is three years, the total number of events required is 263. Based on the log-rank test, the total number of subjects required to prove HR is 0.67 with a two-sided alpha of 0.05 and 90% power is 494. 520 patients are finally studied, considering 5% drop-out. Clinical trial identification: NCT05827523; April 25, 2023. Legal entity responsible for the study: The authors. Funding(s): National Cancer Center, Republic of Korea. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023

Lim, P. C. (2022). "A review of robotic surgery in the management of recurrent ovarian carcinoma: indication and techniques." European Journal of Gynaecological Oncology 43(4): 1-11.
	Background: Treatment of recurrent ovarian cancer may consist of salvage chemotherapy or secondary cytoreductive surgery. Retrospective studies suggest that radical secondary cytoreduction resulting in no macroscopic disease (R0) after completion of surgery benefits patients and prolongs survival. The role of robotic-assisted secondary cytoreductive surgery (RASCS) is in its infancy. The aim of this manuscript is to review the literature regarding the role, the indication, and the techniques of RASCS and to summarize the published perioperative, postoperative, and oncologic outcomes of RASCS. Method(s): A comprehensive systemic review was conducted in the PubMed, MEDLINE, EMBASE, and Google Scholar databases from 1 January 1980 through 31 December 2021. Keywords searched were "ovarian cancer", "recurrence", "robotic-assisted secondary debulking/cytoreductive surgery", "morbidity and mortality of secondary cytoreductive surgery", "indications for secondary cytoreductive", and combinations of these terms. Studies selected and analyzed included randomized controlled trials (RCTs) as well as prospective and retrospective anlayses and case series. RASCS procedures and techniques are described. Result(s): Several retrospectives, meta-analyses and prospective randomized trials suggest that optimal secondary cytoreductive surgery is associated with extended progression-free and overall survival. Preoperative selection criteria, such as Memorial Sloan Kettering (MSK) criteria and AGO (Arbeitsgemeinschaft Gynaekologische Onkologie) scores demonstrate that clinical-pathological factors can predict optimal secondary cytoreductive surgery and correlate with improved progression-free survival and overall survival. The surgical procedures that are required in secondary cytoreductive surgery can be complex. Limited retrospective studies have demonstrated that secondary cytoreductive surgery utilizing a robotic surgical platform can achieve the same rate of optimal cytoreductive surgery as open laparotomy with decreased morbidity. The effect of RASCS on progression-free and overall survival has not been established. Conclusion(s): Early literature reports indicate that RASCS, in selected patients, can be applied for surgical treatment of recurrent ovarian cancer without compromising morbidity; long-term studies are warranted to determine the effect on progression-free and overall survival.Copyright © 2022 The Author(s).

Lim, S., et al. (2021). "A novel, out-of-pocket, cost-effectiveness analysis comparing a frontline niraparib-for-all to a biomarker-based strategy in patients with advanced ovarian cancer." Gynecologic Oncology 162(Supplement 1): S77.
	Objectives: Niraparib has been FDA approved as frontline maintenance therapy (FMT) for advanced-stage ovarian cancer regardless of biomarker status. A recently published preferences study demonstrated that, on average, ovarian cancer patients are willing to pay (WTP) $424 per month for an additional 6 months of progression-free survival (PFS) and $6 per month if the PFS benefit is only 2 months. The objective of this study is to determine whether a niraparib-for-all FMT approach is cost-effective compared to a biomarker-based strategy (BBS) from a patient out-of-pocket (OOP) cost perspective. Method(s): A Markov-based decision model simulating the publicly available PRIMA trial results was used to evaluate the cost-effectiveness of two FMT strategies from a patient perspective: (1) niraparib for all (niraparib-for-all) and (2) BBS, defined as niraparib only for deleterious germline/somatic BRCA mutations and homologous recombination deficient (HRD)+ tumors. Monthly OOP drug costs were estimated for commercially insured beneficiaries with ovarian cancer using MarketScan (2014 - 2017) and for Medicare beneficiaries using Surveillance, Epidemiology, and End Results (SEER)-Medicare (2014-2016). The median OOP cost for any PARP inhibitor given during the time period were aggregated. OOP costs fortoxicities were incorporated into the model as emergency department copay costs. For comparison to previously reported patient WTP data, cost-effectiveness was reported as the incremental cost-effectiveness ratio (ICER) in U.S. dollars per quality-adjusted progression-free month (QA-PFM) gained between strategies. Result(s): The median monthly OOP cost of PARP maintenance was $43 for commercially insured beneficiaries and $694 for Medicare beneficiaries. In the model, niraparib-for-all was more costly ($638 versus $362 for commercial insurance; $5841 vs $1029 for Medicare) and more effective (11-month PFS vs 9.6-month PFS) than BBS. For patients with commercial insurance, niraparib-for-all had an ICER of $200/QA-PFM compared to BBS, and could be considered potentially cost-effective compared to a previously published patient WTP of $424/QA-PFM. For patients with Medicare, niraparib-for-all had an ICER of $3,213/QA-PFM compared to BBS and is not cost-effective. A monthly OOP cost of $90 or less wound render niraparib-for-all cost-effective based on the published WTP threshold. Conclusion(s): For patients with private insurance, accounting for only OOP costs and assuming a PFS benefit of approximately 6 months, niraparib-for-all could be considered cost-effective, falling within patients' WTP, with an ICER of $200/QA-PFM compared to BBS. However, for patients with Medicare, both strategies incur considerably higher OOP expenses, and niraparib-for-all cannot be considered cost-effective. These results highlight the stark differences in financial burden on patients depending on their insurance coverage. Future cost-effectiveness studies should incorporate patient OOP costs and willingness to pay so that relative financial burden can be used to facilitate treatment conversations.Copyright © 2021 Elsevier Inc.

Lim Wei, H., et al. (2022). "Manifestation and management of intravenous leiomyomatosis: A systematic review of the literature." Surgical Oncology 45: 101879.
	Intravenous leiomyomatosis (IVL) is characterized by the presence of vascular extension and invasion of benign smooth muscle lesions in a worm-like manner from uterine fibroids into the systemic vasculature system. Surgery with complete tumour resection remains the main treatment approach, however both treated and untreated of this disease is associated with high morbidity and mortality. The aim of this systematic review is to highlight the systemic manifestations and surgical management of IVL. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Lima, C. T. S., et al. (2020). "Pelvic floor ultrasound finds after episiotomy and severe perineal tear: systematic review and meta-analysis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians: 1-12.
	AIM: Vaginal delivery is a well-known risk factor for pelvic floor muscle (PFM) injuries, mainly when associated to prolonged labor, instrumental birth and perineal trauma such as episiotomy and perineal tears. The purpose of this meta-analysis was to test the hypothesis that episiotomy and severe perineal tear may increase the risk of pelvic floor damage. METHODS: We performed a systematic literature search through electronic databases including MEDLINE via PubMed, LILACS via BVS, Embase via Elsevier and Cochrane Library up to January 2019. We included articles that reported as outcome one or more morphological aspects of the PFM evaluated by ultrasonography in primiparous women three to 24 months postpartum. This review is registered in the PROSPERO database (registration number: CRD42017075750). RESULTS: the final selection was composed of 18 articles for the systematic review, and 10 for the meta-analysis. Women with levator ani muscle (LAM) avulsion were 1.77 times more likely to have undergone episiotomy (OR = 1.77, CI 95% 1.25-2.51, five trials), 4.31 times more likely to have severe perineal tear (OR = 4.31, CI 95% 2.34-7.91, two trials). Women with defects in the anal sphincters were 2.82 times more likely to have suffered severe perineal tear (OR = 2.82, 95% CI 1.71-4.67, three trials). CONCLUSIONS: Both episiotomy and severe perineal tear are risk factors for LAM avulsion and anal sphincter injury, and this can be useful for identifying women who are at greater risk of developing PFM dysfunctions.

Limited, I. V. F. and C. Mexico New Hope Fertility (2022). Evaluation of SiD's System for Improving Assisted Reproduction Treatments.
	No Results Available Device: Software assisted selection of individual spermatozoa for intracytoplasmic sperm injection Fertilization rate|Blastocyst formation rate|Usable blastocyst formation rate|Ploidy status|Biochemical pregnancy|Clinical pregnancy Female Not Applicable 60 Other Allocation: Non-Randomized|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment P002-SP002 October 31, 2022

Lin, G., et al. (2023). "Clinical efficacy of acupuncture for diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials." Frontiers in Endocrinology 14: 1136121.
	Objective: To evaluate the clinical efficacy of acupuncture for the treatment of diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs). Method(s): Nine databases from their inception to December 6th, 2022, were comprehensively searched to retrieve RCTs related to the clinical efficacy of acupuncture for the treatment of DOR. The outcomes of interest were sex hormones level and antral follicle count (AFC). Risk of Bias (RoB) was adopted to assess the quality of the included trials. Result(s): A total of 13 RCTs involving 787 patients were included in this meta-analysis. The review of available evidence revealed acupuncture produced a significant efficacy in decreasing follicle-stimulating hormone (FSH) levels (SMD = -1.07, 95%CI [-1.79, -0.36], p = 0.003), FSH/LH ratio (MD = -0.31, 95%CI [-0.54, -0.09], p = 0.006) and increasing anti-Mullerian hormone (AMH) levels (SMD = 0.25, 95%CI [-0.00, 0.49], p = 0.05), along with AFC (MD = 1.87, 95%CI [0.96, 2.79], p < 0.0001) compared to controls. Compared with electro-acupuncture treatment, manual acupuncture was superior in reducing FSH levels, FSH/LH ratio, and increasing AMH levels and AFC (p < 0.05). A notable association was also seen when acupuncture was combined with traditional Chinese medicine therapy for improving FSH levels, FSH/LH ratio, and AFC (p < 0.05). Besides, a high dose of acupuncture (>=10 acupoints) was more conducive to ameliorating FSH levels, FSH/LH ratio, and AFC (p < 0.05) than a low dose of acupuncture (<10 acupoints). Substantial heterogeneity existed among studies. Conclusion(s): Acupuncture may have significant clinical potential for patients with DOR in terms of improving sex hormones level and increasing AFC, although the evidence is drawn with high heterogeneity. This finding suggests that more rigorous trials conducted in diverse regions worldwide are necessary to identify the efficacy of acupuncture for patients diagnosed with DOR. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42023402336.Copyright © 2023 Lin, Liu, Cong, Chen and Xu.

Lin, G., et al. (2023). "The clinical value of progestin-primed ovarian stimulation protocol for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis." Frontiers in Endocrinology 14: 1232935.
	Background: To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment. Method(s): Nine databases were searched until May 24, 2023, to identify relevant studies. Forest plots were used to present the results of this meta-analysis. Begg's and Egger's tests were applied to estimate publication bias. Subgroup and sensitivity analysis were performed to check the potential sources of heterogeneity and verify the robustness of the pooled results, respectively. Result(s): A total of 14 studies with 4182 participants were included for meta-analysis. There was evidence of a statistically notable increase in clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], p = 0.05), optimal embryos rate (OR = 1.50, 95%CI [1.20, 1.88], p = 0.0004), and cumulative pregnancy rate (OR = 1.73, 95%CI [1.14, 2.60], p = 0.009), the duration and the amount of gonadotropin required (MD = 1.56, 95%CI [0.47, 2.66], p = 0.005; SMD = 1.51, 95%CI [0.90, 2.12], p < 0.00001), along with decrease cycle cancellation rate (OR = 0.78, 95%CI [0.64, 0.95], p = 0.02), luteinizing hormone (LH) level on the day of hCG (SMD = -0.81, 95%CI [-1.10, -0.53], p < 0.00001), and premature LH surge rate (OR = 0.10, 95%CI [0.07, 0.15], p < 0.00001) when PPOS was used. No evidence for publication bias within results was revealed. Conclusion(s): Based on evidence-based results, PPOS protocol seems to improve IVF/ICSI outcomes for women with DOR. More research with larger sample sizes and rigorous designs are required to further explore the value of PPOS among women diagnosed with DOR. Systematic review registration: www.crd.york.ac.uk, identifier CRD42023430202.Copyright © 2023 Lin, Zhong, Li, Liu and Xu.

Lin, G., et al. (2023). "Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis." Frontiers in Endocrinology 14: 1215755.
	Objective: To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF).; Methods: Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook.; Results: Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol ( p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG ( p < 0.05).; Conclusion: For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future.; Systematic Review Registration: https://www.crd.york.ac.uk PROSPERO (CRD42023421739).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Lin, Zhong, Li and Xu.)

Lin, H., et al. (2020). "The effectiveness of online interventions for patients with gynecological cancer: An integrative review." Gynecologic Oncology 158(1): 143-152.
	Objective: With advantages of easy accessibility and various multimedia interactivity formats, online interventions have been developed to improve health outcomes for patients with a variety of gynecological cancers, but evidence regarding their effectiveness for such patients is not well-understood. This review aimed to synthesize study findings that were published in English or Chinese regarding the effectiveness of online interventions on the quality of life, symptom distress, social support, psychological distress, sexual well-being, and body image in patients with gynecological cancer. Method(s): This integrative review adhered to five steps, including problem identification, literature search, quality appraisal, data analysis, and presentation. Ten electronic databases (MEDLINE, ScienceDirect, SpringerLink, PubMed, Wiley Online Journals, Web of Science, OVID, CINAHL Plus with Full Text, China National Knowledge Infrastructure, and Cochrane Library) were searched from the inception of each database to April 2019 in accordance with the rigid and explicit inclusion and exclusion criteria. Version 2018 of the Mixed Methods Appraisal Tool was used for the quality appraisal of the articles. Result(s): Out of 276 articles, 24 potentially eligible articles were initially identified. A manual search retrieved an additional eligible three articles. After nine articles were excluded, ten quantitative, six qualitative, and two mixed-methods articles were finally included. Online interventions improved quality of life and body images in patients with gynecological cancer, but there were inconclusive effects on symptom distress, social support, psychological distress, and sexual well-being. Conclusion(s): Online interventions have been increasingly used as clinically promising interventions to promote health outcomes among patients with gynecological cancer. Studies with more rigorous designs and sufficient sample sizes are needed to elucidate the effectiveness of such online interventions. Healthcare workers can incorporate existing or new online interventions into their routine care to improve health outcomes for patients with gynecological cancer.Copyright © 2020 The Authors

Lin Kent, Y.-H., et al. (2023). "Analgesic Efficacy of Acupuncture on Chronic Pelvic Pain: A Systemic Review and Meta-Analysis Study." Healthcare (Basel, Switzerland) 11(6).
	Chronic pelvic pain (CPP) is the pain occurred in the pelvic region longer than six months. The monotherapy of medicine may not adequate for the pain management of CPP and multidisciplinary approaches have been more recommended. The aim of this study is to evaluate the pain management efficacy of acupuncture compared with a control group on CPP. The articles of randomized controlled trial on CPP in PubMed and Embase databases were screened between January 2011 and September 2022 without language restriction to evaluate the treatment efficacy of acupuncture. The visual analogue scale/numerical rating scale (VAS/NRS) and total pain scores of National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) were served as outcome variables. Post-intervention mean scores were extracted and pooled for meta-analysis. Seventeen studies including 1455 patients were selected for meta-analysis. Both total pain scores of NIH-CPSI and VAS/NAS data revealed significant lower pain level in the acupuncture group than in the control group. Moreover, monotherapy with acupuncture revealed a significantly lower pain level than in the control group in both total pain scores of NIH-CPSI and VAS/NRS. These results indicated that acupuncture may have beneficial effects on pain management for CPP, even when administrated as a monotherapy.

Lin, L., et al. (2019). "Quality of Life, Adverse Events, and Reintervention Outcomes after Laparoscopic Radiofrequency Ablation for Symptomatic Uterine Fibroids: A Meta-Analysis." Journal of Minimally Invasive Gynecology 26(3): 409-416.
	In this review, we assessed the short-term (3 and 6 months) and long-term (12, 24, and 36 months) symptom relief and quality of life improvement, procedure-related adverse event rate, reintervention rate, and days missed from work after laparoscopic radiofrequency ablation. Using MeSH keywords "uterine fibroid" and "ablation technique," a systematic search was performed in PubMed, Ovid, Embase, Cochrane Library, and Clinicaltrials.gov. Studies consisting of uterine fibroid symptoms and quality of life scores were considered eligible. Both comparative and noncomparative studies were included. Using a random-effects model, a meta-analysis was performed. Eight studies with a total of 581 patients were finally included in our review. Based on validated questionnaires, quality of life improved significantly until 36 months after laparoscopic radiofrequency ablation therapy, with a maximum improvement (Health-Related Quality of Life [HRQL] questionnaire score of +41.64 [95% confidence interval (CI), 38.94-44.34] and a transformed Symptom Severity Score [tSSS] of -39.37 [95% CI, 34.70-44.04]) at 12 months after laparoscopic radiofrequency ablation. All subscales of quality of life improved significantly, and most of the changes remained stable in long-term follow-up. The overall reintervention rate was 4.39% (95% CI, 1.60%-8.45%), and the median uterine volume reduction was 69.17 cm³ (95% CI, 35.87-102.46 cm³).The overall procedure-related adverse events rate was 1.78% (95% CI, 0.62%-3.53%), and patients missed an average of 4.35 days (95% CI, 2.55-6.15 days) of work. In conclusion, laparoscopic radiofrequency ablation therapy is an efficacious way to treat small-sized and nonpedunculated symptomatic uterine fibroids, providing stable long-term symptom relief and quality of life improvement with a low risk of adverse events and reintervention and just a few days of missed work. (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

Lin, P. J., et al. (2023). "Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors." JNCCN Journal of the National Comprehensive Cancer Network 21(2): 153-162.
	Background: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. Patients and Methods: Cancer survivors (n5410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. Result(s): Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size 5 20.33; all P#.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P#.05). Conclusion(s): A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.Copyright © JNCCN-Journal of the National Comprehensive Cancer Network.

Lin, Q., et al. (2020). "The value of systematic lymphadenectomy during debulking surgery in the treatment of ovarian cancer: a meta-analysis of randomized controlled trials." Journal of Ovarian Research 13(1): 56.
	Background: The therapeutic value of systematic lymphadenectomy during debulking surgery for ovarian cancer remains controversial. We conduct this meta-analysis to evaluate the significance of systematic lymphadenectomy in patients treated with optimal cytoreduction for ovarian cancer.; Method: The PubMed, Medline, Embase, Cochrane Library and Web of Science databases were searched up to October 2019. Only English-language publications of randomized controlled trials (RCTs) that investigated the role of systematic lymphadenectomy in patients with ovarian cancer were selected for this analysis. For overall survival (OS) and progression-free survival (PFS), pooled hazard ratios (HR) with 95% confidence intervals (CIs) were calculated; for complications rate, we calculated pooled risk ratio (RR) with 95% confidence interval (CI). Statistical heterogeneity was assessed using both the I 2 and chi-square tests. In cases of I 2 being larger than 50%, a random-effect model was used, otherwise a fixed-effect model was used.; Results: Four RCTs involving 1607 patients were included in the present analysis. There was no difference in OS between systematic lymphadenectomy and unsystematic lymphadenectomy (HR = 1.00; 95% CI = 0.94, 1.07; p = 0.90). Similarly, no significant difference was observed in PFS between these two groups (HR = 0.97; 95% CI = 0.87, 1.08; p = 0.62). And postoperative complications occurred more frequently in the systematic lymphadenectomy group (RR = 1.50; 95% CI = 1.34, 1.68; p < 0.00001).; Conclusion: Systematic lymphadenectomy in patients with optimally cytoreduced ovarian cancer was not associated with longer overall or progression-free survival than unsystematic lymphadenectomy and was associated with a higher incidence of postoperative complications.

Lin, S. and D. Lin (2022). "Comparative effect of various psychosocial intervention for menopausal symptoms in breast cancer patients: a network Meta-analysis."
	
Lin, W., et al. (2022). "Kuntai capsules in treatment of premature ovarian failure: A systematic review and meta-analysis." Journal of Herbal Medicine 31: 100524.
	Objective: To assess the effectiveness and safety of Kuntai capsules (KTC) in treatment of premature ovarian failure (POF). Method(s): A systematic review and meta-analysis of randomized controlled trials studied KTC alone or combined with hormone therapy (HT) used for treating POF. PubMed, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, Chinese Scientific Journal and Wanfang database were searched until July 2019. The Cochrane risk of bias method was used to assess the quality of the included studies, a meta-analysis was conducted with Review Manager 5.3 software and the level of evidence was rated by using GRAEDpro 3.6 software. Result(s): A total of 14 RCTs (1257 participants) were included. Meta-analysis indicated that KTC can significantly improve the total clinical effective rate (P < 0.00001) and the serum hormone levels (P < 0.00001), with no statistically significant report of adverse reactions (P = 0.07) compared with HT. By the subgroup meta-analysis, the results of KTC combined with HT group were similar compared with the original analysis in the serum hormone level (P < 0.00001), and the KTC alone group were better in FSH and LH level (P < 0.00001) but not in E2 level (P = 0.22). Based on the GRADE system for grading, the qualities of the evidence were not high. Conclusion(s): KTC may be effective for POF treatment, and lower risk of side effects. More high-quality articles are needed to provide more reliable sources and data to evaluate the clinical efficacy of KTC in the future.Copyright © 2021 Elsevier GmbH

Lin, Y., et al. (2023). "Chinese Herbal Medicine, Alternative or Complementary, for Endometriosis-Associated Pain: A Meta-Analysis." The American journal of Chinese medicine 51(4): 807-832.
	Current medical treatments for endometriosis-associated pain (EAP) have limitations, including symptom recurrence and hormonal side effects. For this reason, it is important to elucidate any alternative or complementary treatments available, while Chinese herbal medicine (CHM) shows potential to be this treatment. This study aims to provide evidence for the efficacy and safety of CHM for EAP. Randomized control trials comparing CHM to other treatments for EAP in women with endometriosis were considered eligible, and they were searched for in Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, as well as in the Chinese databases Sino-Med and CNKI, from inception to October 2021. Numerous outcomes were put through meta-analysis using a weighted mean difference and a 95% CI, and the results of dichotomous data were presented as a pooled RR with a 95% CI. A total of 34 eligible studies with 3389 participants were included. Compared with no treatment, there was a statistically significant pooled benefit of CHM on dysmenorrhea at the end of 3-month treatment, and these effects continued for 3 months, but not 9 months, after treatment. Compared with conventional therapy, a significant difference was found in the levels of pelvic pain with a lower rate of hot flush and irregular vaginal bleeding at the end of treatment for 3 months, but not after treatment. Comparing combined treatment with CHM and conventional therapy with conventional therapy alone, significant decreases were found in dysmenorrhea, dyspareunia, and pelvic pain after a 3-month treatment cycle, and in dysmenorrhea after a 4-month treatment cycle with a lower hot flash rate. In conclusion, CHM, used alone or in combination with conventional therapies, appears to have benefits in relieving EAP with fewer side effects than traditional treatment.

Lin, Y. H., et al. (2021). "Focusing on long-Term complications of mid-urethral slings among women with stress urinary incontinence as a patient safety improvement measure: A protocol for systematic review and meta-Analysis." Medicine (United States) 100(24): E26257.
	Background: There are 3 different types of mid-urethral sling, retropubic, transobturator and single incision performed for women with stress urinary incontinence. Prior studies comparing these three surgeries merely focused on the successful rate or efficacy. But nevertheless, what is more clinically important dwells upon investigating postoperative complications as a safety improvement measure. Method(s): A systematic review via PubMed, Ovid, and the Cochrane Database of Systematic Review and studies were applied based on the contents with clearly identified complications. Selected articles were reviewed in scrutiny by 2 individuals to ascertain whether they fulfilled the inclusion criteria: complications measures were clearly defined; data were extracted on study design, perioperative complications, postoperative lower urinary tract symptoms, postoperative pain, dyspareunia, and other specified late complications. Result(s): A total of 55 studies were included in the systemic review. Perioperative complications encompassed bladder perforation, vaginal injury, hemorrhage, hematoma, urinary tract infection. There were postoperative lower urinary tract symptoms including urine retention and de novo urgency. Furthermore, postoperative pain, tape erosion/ extrusion, further stress urinary incontinence surgery, and rarely, deep vein thrombosis and injury of inferior epigastric vessels were also reported. Conclusion(s): Complications of mid-urethral sling are higher than previously thought and it is important to follow up on their longterm outcomes; future research should not neglect to address this issue as a means to improve patient safety.Copyright © 2021 Lippincott Williams and Wilkins. All rights reserved.

Lindermann Peressoni, T., et al. (2022). "Influence of phytoestrogens on endometrial thickness: a systematic review and meta-analysis." Climacteric : the journal of the International Menopause Society 25(2): 118-127.
	The objective of this systematic review was to evaluate the influence of the use of phytoestrogens on variations in endometrial thickness in postmenopausal women. Randomized controlled trials were searched in the following electronic databases until March 2020: MEDLINE, Embase, Cochrane Library, Web of Science and LILACS. We used the terms 'phytoestrogens' and 'endometrium' or 'endometrial hyperplasia' to search for relevant trials. The data were analyzed using RevMan 5.3 software. A total of 10 studies involving 1476 patients were included. The difference in endometrial thickness was evaluated in 10 studies, with a total of 805 participants in the phytoestrogen group and 761 in the control group. Such a difference was not significant between groups after 3 months (standardized mean difference [SMD] 0.00, 95% confidence interval [CI] - 0.37 to 0.37; I 2 = 63%), 6 months (SMD -0.30, 95% CI -0.79 to 0.19; I 2 = 70%), 12 months (SMD -0.02, 95% CI 0.22 to -0.18; I 2 = 0%) and 24 months (SMD -0.09, 95% CI -0.25, 0.08; I 2 = 0%) of use. Our meta-analysis shows no changes in endometrial thickness in women using phytoestrogens. Evidence is still uncertain owing to the presence of heterogeneity among the studies currently available, whose reported outcomes cover a period between 3 and 6 months.

Lindley, B.-C., et al. (2022). "Intranasal oxytocin administration improves mood in new mothers with moderate low mood but not in mothers with elevated symptoms of postnatal depression: A randomised controlled trial." Journal of Affective Disorders 300: 358-365.
	Background: Oxytocin (OT) is a neuropeptide hormone that has anxiolytic and antidepressant effects, and positive effects on social affiliation and behaviour, particularly in parenting and attachment relationships. In women with postnatal depression (PND), each of these are reduced. This study investigated if OT administration reduces low mood in new mothers with PND and across the low mood spectrum.; Design: A double-blind, placebo-controlled, randomised controlled-trial, within-subjects, cross-over design was conducted.; Participants: Mothers (N = 58) between 3 and 9 months postpartum. Participants were screened for traits of PND on the Edinburgh Postnatal Depression Scale (EPDS) and assigned into 2 groups: probable PND cases (N = 26, scoring ≥9) and controls (N = 32, scoring ≤9).; Method: Participants rated their current mood on the Positive and Negative Affect Scale (PANAS) at Baseline (before nasal administration), Condition 1 (after first OT/Placebo administration) and Condition 2 (after second OT/Placebo administration).; Results: OT administration did not affect mood in women with PND scores above the cut-off point but significantly reduced negative mood in those scoring below the cut-off point. To explore if a subgroup was driving this, we compared participants with mild, moderate and severe scores on the EPDS. OT administration significantly reduced negative mood in women with moderate low mood scores on the EPDS.; Limitations: PND was assessed by the EPDS, rather than a clinical diagnosis.; Conclusion: These results illustrate individual differences in response to OT administration and suggest that OT administration may offer treatment benefit to new mothers who report moderate sub-clinical levels of depression. (Copyright © 2021. Published by Elsevier B.V.)

Lindner, L. H., et al. (2022). "Transcervical Fibroid Ablation (TFA) with the Sonata System: Updated Review of a New Paradigm for Myoma Treatment." Current Obstetrics and Gynecology Reports 11(3): 238-248.
	Purpose of Review: This paper provides an update of the recent evidence related to transcervical fibroid ablation (TFA) with the Sonata System. Recent Findings: An additional 27 papers representing over 400 women and more than 800 treated fibroids have been published. These demonstrate consistent, positive results, representing multiple prospective clinical trials, subgroup analyses, health economic analyses, case series, and systematic reviews of TFA. These include a 147-patient prospective clinical trial of TFA (the SONATA Clinical Trial) that demonstrated sustained symptom relief and an 8.2% cumulative reintervention rate through 3 years, a long-term study (VITALITY) confirming durable symptom relief with an 11.8% reintervention rate over > 5 years of mean follow-up, a clinical trial (OPEN) suggesting minimal potential for intrauterine adhesiogenesis post-TFA, preliminary results of a global registry (SAGE), and two subgroup analyses of TFA reporting favorable and safe outcomes in women with large fibroids > 5 cm in diameter. Three comparative health economic studies demonstrate favorable economic outcomes against both myomectomy and hysterectomy. A recent ACOG Practice Bulletin also noted equivalent outcomes for transcervical, laparoscopic, and transvaginal fibroid ablation. Summary: Accumulated clinical evidence, including systematic reviews and longitudinal prospective clinical trials, continues to confirm the safety and efficacy of TFA in women with symptomatic fibroids, including myomata > 5 cm. As a transcervical treatment modality that can safely address all nonpedunculated uterine fibroid types, the continued evidence base confirms TFA as an innovative and useful treatment option that meets a significant unmet clinical need, including among underserved populations, delivering significant durable reductions in fibroid symptoms.Copyright © 2022, The Author(s).

Lindsay, F., et al. (2024). Fenofibrate in Patients With Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma.
	No Results Available Drug: Fenofibrate|Procedure: Cervical Conization|Procedure: Hysterectomy|Radiation: Chemoradiation Change in p53 levels|Change in tumor metabolic status|Fenofibrate tolerability Female Phase 1 24 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CASE3822 May 31, 2025

Ling, F. (2021). "The effect of anesthesia with propofol combined with dizocine in patients undergoing painless induced abortion." 当代医药论丛 19(11): 120‐121.
	Objective: To analyze the effect of anesthesia with propofol combined with dezocine on patients undergoing painless induced abortion. Methods: From November 2019 to February 2020, 250 patients who received painless artificial abortion in Guangxi Zhuang Autonomous Region Nationalities Hospital were randomly divided into control group and study group. During the operation, the patients in the control group were anesthetized with propofol, and the patients in the study group were anesthetized with propofol combined with dezocine. Then, the hemodynamic indexes, various inflammatory indexes and the occurrence of adverse reactions were compared between the two groups of patients. Results: Compared with the control group, the levels of MAP, IL‐6 and TNF‐α in the study group were lower, and their HR was slower, P<0.05. The incidences of limb movement, respiratory depression and nausea and vomiting were compared between the two groups, P>0.05). CONCLUSION: Propofol combined with dezocine is effective in anesthesia for patients undergoing painless induced abortion, and the medication is safe.

Ling, G., et al. (2023). "Acupuncture for hot flushes in women with breast cancer: An overview of systematic reviews and Meta-analysis."
	
Liontos, M., et al. (2019). "Systemic therapy in cervical cancer: 30 years in review." Critical Reviews in Oncology/Hematology 137: 9-17.
	Advanced-inoperable cervical cancer is a challenging entity due to increased percentage of locoregional and distant recurrences. Furthermore, recurrent cervical cancer not amenable to radical treatment as well as de novo metastatic disease are considered incurable with dismal prognosis. Well-designed clinical trials conducted during the last 30 years have revealed the active chemotherapeutic agents as well as their optimal combinations. The rational approach that has led to the current treatment algorithms as well as the introduction of targeted therapies based on the knowledge of the molecular pathogenesis of the disease are discussed in this review.Copyright © 2019 Elsevier B.V.

Lírio, J., et al. (2019). "Antifungal (oral and vaginal) therapy for recurrent vulvovaginal candidiasis: a systematic review protocol." BMJ Open 9(5): e027489.
	Introduction: Vulvovaginal candidiasis (VVC) is frequent in women worldwide and usually responds rapidly to topical or oral antifungal therapy. However, some women develop recurrent vulvovaginal candidiasis (RVVC), which is arbitrarily defined as four or more episodes every year. RVVC is a debilitating, long-term condition that can severely affect the quality of life of women. Most VVC is diagnosed and treated empirically and women frequently self-treat with over-the-counter medications that could contribute to an increase in the antifungal resistance. The effective treatment of RVVC has been a challenge in daily clinical practice. This review aims to assess the efficacy of antifungal agents administered orally or intravaginally for the treatment of RVVC, in order to define clinical practices that will impact on the reduction of the morbidity and antifungal resistance.; Methods and Analysis: A comprehensive search of the following databases will be carried out: PubMed, Embase, Scopus, Web of Science, Scientific Electronic Library Online (SciELO), the Cochrane Central Register of Controlled Trials (CENTRAL), Biblioteca Virtual em Saúde (Virtual Health Library)/Biblioteca Regional de Medicina (Regional Library of Medicine) (BVS/BIREME), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and in the clinical trials databases (www.trialscentral.org; www.controlled-trials.com; www.clinicaltrials.gov). The risk of bias will be assessed according to the Cochrane Risk of Bias tool. We will perform data synthesis using the Review Manager (RevMan) software V.5.2.3. To assess heterogeneity, we will compute the I2 statistic.; Ethics and Dissemination: This study will be a review of published data and it is not necessary to obtain ethical approval. Findings of this systematic review will be published in a peer-reviewed journal.; Trial Registration Number: CRD42018093817.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lisa, H., et al. (2023). "Burden of illness in women with endometriosis-associated chronic pelvic pain."
	
Líška, D. and J. Záhumenský (2020). "Conservative treatment options for polycystic ovary syndrome: the importance of exercise." Ceska gynekologie 85(6): 430-435.
	Aim: The main aim of the article is inform about benefits of rehabilitation in the treatment of polycystic ovary syndrome (PCOS).; Study Type: Review article.; Methods: Search for meta-analyzes and systematic review in Pubmed, Medline, Scopus databases.; Results: Insulin resistance plays a potential role in the pathogenesis of PCOS. Lifestyle modification (including physical activity and diet) may help alleviate the symptoms of PCOS, as lifestyle factors may reduce insulin resistance and improve metabolism and reproductive function. The benefit of exercise in women with PCOS is also associated with other significant benefits such as improved anxiety, metabolic syndrome and improved regularity of the menstrual cycle.; Conclusion: Rehabilitation is an important part of therapy in patients with PCOS. Aerobic, strength and interval exercises has a significant benefit in the treatment of polycystic ovary syndrome.

Litvinova, E., et al. (2020). "Efficacy, safety, quality assurance of isomers of non-steroidal anti-inflammatory drugs: Dexketoprofen and dexibuprofen." Journal of Global Pharma Technology 12(11): 118-129.
	The aim of this work is to analyze and systematize data on efficacy, safety, and quality assurance for NSAID isomers-dexketoprofen and dexibuprofen. Studies were conducted using databases on the Internet: PubMed; Food and Drug Administration, European Medicines Agency. It has used retrospective, logical, systematic and analytical methods. The results of a multifaceted analysis of sources of data of clinical use proved the high analgesic efficacy of dexketoprofen and dexibuprofen in acute and chronic pain of various etiologies, such as toothache, dysmenorrhea, pain after surgery, muscle pain, headache, back pain, pain from bone metastases, etc. To achieve the effect obtained with the use of 1 dose of racemic NSAIDs, half the dose of their active isomers is sufficient. The high clinical effectiveness of dexketoprofen, dexibuprofen combines with their relative tolerance, in particular from the gastrointestinal tract. In large part, the safety of dexketoprofen is due to the presence of only the active S (+) - enantiomer of ketoprofen, dexibuprofen is due to the presence of only active S (+) - ibuprofen, which eliminates the side effects associated with the influence of the R (-) - enantiomers. The results of the analysis of quality assurance of generic dexketoprofen (class 1 of biopharmaceutical classification system) and dexibuprofen (class 2 of biopharmaceutical classification system) during the biowaiver procedure are systematized. It has been shown that not only high permeability and high solubility, but also the composition of the drug excipients are important for pharmaceutical equivalence in vitro. Based on the results research findings presented, it is possible to optimize the technological process and analytical methods, which allows taking into account critical factors and ensuring the quality of the medicine and its bioequivalence to the reference drug.Copyright © 2020 Journal of Global Pharma Technology. All rights reserved.

Liu, C., et al. (2020). "The Safety and Efficacy of Intra-Arterial versus Intravenous Neoadjuvant Chemotherapy in Patients with Locally Advanced Cervical Cancer: A Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2020: 5023405.
	Objective: The aim of this study was to evaluate the safety and efficacy of intra-arterial versus intravenous neoadjuvant chemotherapy for the management of patients with locally advanced cervical cancer.; Methods: The PubMed, EMBASE, PMC, Web of Science, and Cochrane databases were searched to identify correlational studies published in English. Prospective controlled studies that evaluated the treatment effect of intra-arterial neoadjuvant chemotherapy or intravenous neoadjuvant chemotherapy in patients with locally advanced cervical cancer were pooled for a meta-analysis.; Results: A total of three eligible studies with 112 patients with locally advanced cervical cancer were eventually included in this analysis. The baseline regimen of neoadjuvant chemotherapy was platinum-based chemotherapy. The total clinical response rate was 71.4%, and the overall pathological complete response (CR) rate was 11.5%. The grade 3/4 toxicity rate was 27.2%. In the intra-arterial group, the response rate was 83.1% (CR, 22.0%; partial response (PR), 61.0%), which was significantly higher than 58.5% (CR, 11.3%; PR, 47.2%) in the intravenous group ( P =0.01). The pathological CR rate was 15.5% in the intra-arterial group, which was higher than 6.5% in the intravenous group. The grade 3/4 toxicity rate was 17.2% in the intra-arterial group, which was higher than the rate of 13.8% in the intravenous group.; Conclusion: Platinum-based neoadjuvant chemotherapy was well tolerated in patients with locally advanced cervical cancer and showed moderate response activity. Compared to intravenous neoadjuvant chemotherapy, intra-arterial neoadjuvant chemotherapy had an evident advantage in terms of the clinical response while maintaining a similar toxicity rate. The clinical efficacy of intra-arterial neoadjuvant chemotherapy deserves further evaluation.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2020 Cheng Liu et al.)

Liu, C., et al. (2021). "The effects of Chinese herbal medicine on the pregnancy outcomes of infertile women with polycystic ovary syndrome undergoing in vitro fertilization-embryo transfer: A systematic review and meta-analysis." Clinical and Experimental Obstetrics and Gynecology 48(5): 1032-1043.
	Background: At present, Chinese herbal medicine (CHM) has already been widely used as an important adjuvant treatment for polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization-embryo transfer (IVF-ET). This systematic review and meta-analysis were designed to evaluate the effects of CHM on the pregnancy outcomes of infertile women with PCOS undergoing IVF-ET. Method(s): We searched seven electronic databases systematically for published articles to January 2021. All randomized controlled trials (RCTs) comparing CHM with blank or placebo for infertile PCOS patients undergoing IVF-ET were included. The measures of treatment effect were the pooled odds ratios (OR) of the clinical pregnancy rate, the abortion rate and the ovarian hyperstimulation syndrome (OHSS) incidence. Result(s): This meta-analysis included 10 studies involving 663 patients comparing CHM with blank or placebo for infertile PCOS patients undergoing IVF-ET. The pooled data showed that CHM could improve the clinical pregnancy rate (OR = 2.41, 95% CI: 1.73-3.35, p < 0.01) and reduce the OHSS incidence (OR = 0.31, 95% CI: 0.18-0.55, p < 0.01) of infertile PCOS patients with IVF-ET treatment. No significant difference in the abortion rate was found between the CHM and control groups (OR = 0.64, 95% CI: 0.23-1.81, p = 0.40). Discussion(s): CHM can be used as an auxiliary treatment for infertile PCOS patients undergoing IVF-ET.Copyright ©2021 The Author(s). Published by IMR Press.

Liu, C., et al. (2022). "Concurrent Chemoradiotherapy Increases the Levels of Soluble Immune Checkpoint Proteins in Patients with Locally Advanced Cervical Cancer." Journal of Immunology Research 2022: 9621466.
	Purpose. Concurrent chemoradiotherapy (CCRT) has been widely applied to locally advanced cervical cancer (LACC) patients, inducing the massive release of antigen and systematic immunomodulatory effects. However, its effect on the soluble immune checkpoint proteins (sICPs) remains unclear, which might play a key role in the immune response. Therefore, the current study explored changes in the levels of 16 sICPs in LACC patients during CCRT. Methods. We prospectively enrolled fifty-one LACC patients treated with CCRT and collected patients' blood before, during and after CCRT. The levels of 16 sICPs were measured using the Luminex platform, and the changes were measured using Friedman test with Bonferroni's posttest. One month after CCRT, the tumor response was evaluated according to the RECIST 1.1 guidelines. Results. The levels of soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) significantly increased during CCRT (P=0.041), while those of the soluble B and T lymphocyte attenuator (sBTLA), sCD40, soluble glucocorticoid-induced tumor necrosis factor receptor ligand (sGITRL), sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and soluble inducible T-cell costimulator (sICOS) significantly increased after CCRT (all P<0.05). Other sICPs showed no significant changes throughout the CCRT (all P>0.05). 41 (80%), 8 (16%), and 2 (4%) patients showed complete response (CR), partial response (PR), and stable disease (SD) after CCRT, respectively. Interestingly, the level of soluble lymphocyte-activation gene 3 (sLAG-3) was significantly higher among the PR/SD patients as compared to the CR after CCRT (P=0.009). Conclusions. This study revealed that CCRT might elevate the serum levels of sTIM-3, sBTLA, sCD40, sGITRL, sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and sICOS in the patients with LACC. The sLAG-3 level was higher in the patients with poor response to CCRT. These findings revealed the dynamic changes in the sICPs levels during CCRT, which might be helpful in designing optimal treatment strategies for LACC patients.Copyright © 2022 Chao Liu et al.

Liu, C., et al. (2020). "Efficacy and safety of repetitive transcranial magnetic stimulation for peripartum depression: A meta-analysis of randomized controlled trials." Psychiatry Research 294: 113543.
	This study aims to summarize and systematically review the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for women with peripartum depression (PPD). Several databases (Wanfang, CNKI, VIP, CBM, PubMed, Embase, Cochrane Library, PsyINFO, Web of Science, and Clinical trial) were searched from inception until April 12, 2020. In total, ten randomized controlled trials (RCTs) met the eligibility criteria and were included in this systematic review. We calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. The aggregated result of 10 trials indicated a significant benefit of rTMS on PPD, and the aggregated result of remission showed significantly positive effects of Test group VS. Control group. In terms of treatment adverse effects, the aggregated result showed no statistical significance of headache and dry mouth between the two groups. The results of the meta-analysis suggest that rTMS is an effective and safe intervention for PPD. Owing to poor methodological quality among the included studies, high-quality multicenter RCTs are needed to further verify the effects of this treatment.Copyright © 2020

Liu, C. H., et al. (2022). "Prenatal distress during the COVID-19 pandemic: clinical and research implications." Archives of Gynecology and Obstetrics 306(2): 397-405.
	PURPOSE: The objective of this study was to identify risk and protective factors related to general prenatal distress and COVID-19-specific prenatal distress to inform intervention targets among women pregnant during the COVID-19 pandemic. METHODS: The study relied on data obtained from U.S. pregnant women (N = 701) who participated in the Perinatal Experiences and COVID-19 Effects (PEACE) Study from May 21 to October 3, 2020. The present cross-sectional study examined the potential risk and protective factors associated with different features of prenatal distress among U.S. pregnant women during the COVID-19 pandemic. RESULTS: Approximately two-thirds of expectant mothers indicated being more stressed about going to the hospital because of COVID-19. Generalized anxiety and PTSD were associated with higher levels of general and COVID-19-specific prenatal distress. Depression symptoms were associated with higher general prenatal distress. Higher levels of distress tolerance were associated with lower levels of general prenatal distress (B = - 0.192, p < .001) and COVID-19-specific prenatal distress (B = - 0.089, p < .05). Higher levels of instrumental social support were marginally associated with lower COVID-19-specific prenatal distress (B = - 0.140, p < 0.1). CONCLUSION: Findings draw attention to prenatal distress experiences during the COVID-19 pandemic, including new types of distress arising from the pandemic itself. Women might benefit from the introduction of interventions such as mindfulness-based or relaxation therapy. Coverage of responsibilities and financial assistance is particularly needed during the COVID-19 pandemic. Limitations include a majority White and high socioeconomic sample. These findings provide specificity regarding potential targets for addressing prenatal distress.

Liu, C. H., et al. (2022). "Unexpected changes in birth experiences during the COVID-19 pandemic: Implications for maternal mental health." Archives of Gynecology and Obstetrics 306(3): 687-697.
	PURPOSE: This study examined the rates of unexpected birth experiences due to the COVID-19 pandemic and its association with women's postpartum mental health symptoms (depression, generalized anxiety, and PTSD). METHODS: Our cross-sectional analysis included postpartum women (N = 506) who reported on birth plan changes attributed to the COVID-19 pandemic through the PEACE (Perinatal Experiences and COVID-19 Effects) Study, an online survey that took place between May 2020 and May 2021. Covariates included sociodemographic variables, number of days since the pandemic, pre-pregnancy mental health history, and protective factors such as social support, distress tolerance, and resilience. RESULTS: Prevalent COVID-19 pandemic changes in the birth experience included not having support people (e.g., partners and friends) permitted to participate in the baby's delivery (33.5%), reduced access to preferred medications before or after delivery (9.7%), unavailable health care providers for the baby's birth as planned (9.6%), and other changes (13.8%). The reduced access to medications was associated with those reporting higher levels of depressive (β = .10, p < .01) and PTSD symptoms (β = .07, p < .05). Separation from their baby for a long period after delivery (β = .10, p < .05) and other changes (β = .10, p < .01) were associated with higher levels of PTSD symptoms. CONCLUSION: Unexpected changes to the birth experience due to the COVID-19 pandemic may have small but persistent effects on depressive and PTSD symptoms. Given increased vigilance and its association with subsequent PTSD, acknowledging any fear of viral contagion within the hospital setting but informing women the plans for ensuring safety may be preventive for later mental health symptomatology.

Liu, C. H., et al. (2022). "Laparoscopic-aid procedure for complicated gynecologic surgery." Taiwanese Journal of Obstetrics and Gynecology 61(2): 195-196.
	
Liu, G., et al. (2022). "A novel combo of niraparib and anlotinib in platinum-resistant ovarian cancer, the final efficacy and safety report of ANNIE study, a phase II, multi-center trial (LBA 2)." Gynecologic Oncology 166(Supplement 1): S47.
	Objectives: Patients with platinum-resistant ovarian cancer have a poor prognosis. Effective treatment options for these patients are limited. In this study (ANNIE), we evaluated the efficacy and safety of niraparib combined with anlotinib in patients with platinum-resistant recurrent (PRR) epithelial ovarian, fallopian tubal, or primary peritoneal cancer. Method(s): The ANNIE trial (ClinicalTrials.gov identifier NCT04376073) was a multicentre, single-arm, phase 2 study. The patients with PRR and the measurable disease were given oral niraparib 300mg/200mg once daily continuously and anlotinib 12mg/10mg/8mg on day 1-14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR) according to RECIST version 1.1. An exploratory analysis of archival peripheral blood was conducted in an attempt to analysis the correlation between circulating tumor markers and prognosis. Result(s): Between May 22, 2020, and April 22, 2021, 40 patients were finally enrolled. The subjects had previously received a median 4 lines (range, 1-9) of chemotherapy. Only 5 subjects had a deleterious germline BRCA1/2 mutation. At the cutoff date of analysis on December 31, 2021, 7 subjects were still on treatment. Thirty-six subjects underwent imaging evaluation. The confirmed best overall response showed 1 case with complete responses, 19 with partial responses, yielding the ORR of 55.6% (95% CI, 38.1%~ 72.1%). The median progression-free survival was 8.3 (95% CI, 5.86~ 10.81) months. The median overall survival was not reached. The most common drug-related adverse events were hypertension (55.0%), leucopenia (45.0%) and hand-foot syndrome (42.5%), and the most common Grade 3/4 events were neutropenia (17.5%), hypertension (12.5%) and anemia (12.5%). No treatment-related death was recorded. Preliminary analysis showed that patients with wild-type PPM1D had more significant changes in tumor size than those with PPM1D mutation (P =0.048). Further analysis of biomarkers and treatment prognostic results is ongoing and released soon. Conclusion(s): Niraparib in combination with anlotinib showed promising antitumor activity and tolerable toxicity in patients with platinum-resistant recurrent ovarian cancer.[Formula presented]Copyright © 2022 Elsevier Inc.

Liu, H., et al. (2022). "The effects of mindfulness-based interventions on anxiety, depression, stress, and mindfulness in menopausal women: A systematic review and meta-analysis." Frontiers in Public Health 10: 1045642.
	BACKGROUND: Mindfulness-based interventions (MBIs) are psychological interventions widely used in menopausal women. Currently, there is no evidence summary on the effectiveness of MBIs on anxiety, depression, stress, and mindfulness in menopausal women. This meta-analysis examines the effectiveness of MBIs in improving anxiety, depression, stress, and mindfulness scores in menopausal women. METHODS: A systematic search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang, using relevant terms such as MBIs as keywords and covering all studies published before March 13, 2022. The outcomes were anxiety, depression, stress, and mindfulness. The screening and extraction of data were conducted by two independent reviewers. RESULTS: A total of 1,138 menopausal women participated in 13 studies. Meta-analysis results showed that MBIs significantly reduced stress in menopausal women (SMD = -0.84, 95% CI: -1.64 to -0.05, p = 0.04), but no statistical differences were found in reducing anxiety (SMD = -0.40, 95% CI: -0.81 to 0.01, p = 0.06) and depression (SMD = -0.19, 95% CI: -0.45 to 0.07, p = 0.16) and in raising the scores of mindfulness (SMD = 0.37, 95% CI: -0.06 to 0.81, p = 0.09) in menopausal women. CONCLUSION: MBIs may reduce stress in menopausal women, but their effect on improving anxiety, depression, and mindfulness needs further validation. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/#recordDetails.

Liu, H., et al. (2022). "Effectiveness of robotic surgery for endometrial cancer: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 305(4): 837-850.
	Background: Our current study was performed aimed at determining the efficacy and safety profile of robotic surgery (RS) compared to laparoscopic surgery (LPS) and laparotomy (LT) in the treatment of endometrial cancer on the basis of relevant studies.; Patients and Methods: A systematic literature search was conducted based on appropriate keywords, using the Embase, Cochrane library, as well as PubMed. Our studiers also reviewed the key pertinent sources among the publications and included associated literatures published by June 2021. Odds ratios (ORs), mean difference (MD), as well as 95% confidence interval (95% CI) for each study were measured for further assessment and synthesis of outcomes.; Results: Thirty studies involving a total of 12,025 patients were eventually included in the current meta-analysis. Compared with LPS, RS could significantly decrease the estimated blood loss, the incidence of intraoperative complications, the length of hospital stay, and the rate of conversion, and increased the rate of readmission. Compared with LT, RS significantly decreased the estimated blood loss, blood transfusion volume, the length of hospital stay, the rate of total, intraoperative and postoperative complications, and the rate of readmission and re-operation, and increased the operative time.; Conclusion: Considering the effects and safety profile of RS in terms of treating endometrial cancer, our study suggest that RS exerts superior outcomes than that of LPS and LT. (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Liu, H., et al. (2023). "An optimization for postpartum depression risk assessment and preventive intervention strategy based machine learning approaches." Journal of Affective Disorders 328: 163-174.
	Background: Postpartum depression (PPD) is one of the most common psychiatric disorders for women after delivery. The establishment of an effective PPD prediction model helps to distinguish high-risk groups, and verifying whether such high-risk groups can benefit from drug intervention is very important for clinical guidance.; Methods: We collected data of parturients that underwent a cesarean delivery. The Control group was divided into a training cohort and a testing cohort. Six different ML models were constructed and we compared their prediction performance in the testing cohort. For model interpretation, we introduced SHapley Additive exPlanations (SHAP). Then, training cohort, ketamine group and dexmedetomidine (DEX) group were classified as high or low risk for PPD by the model. A 1:1 propensity score matching (PSM) was performed to compare the incidence of PPD between two groups in different risk cohorts.; Results: Extreme gradient enhancement (XGB) had the best recognition effect, with an area under the receiver operating characteristic curve (AUROC) of 0.789 (95 % CI 0.742-0.836) in the training cohort and 0.744 (95 % CI 0.655-0.823) in the testing cohort, respectively. A threshold of 21.5 % PPD risk probability was determined. After PSM, the results showed that the incidence of PPD in the two intervention groups was significantly different from the control group in the high-risk cohort (P < 0.001) but not in the low-risk cohort (P > 0.001).; Conclusion: Our study demonstrated that the XGB algorithm provided a more accurate in prediction of PPD risk, and it was beneficial to receive early intervention for the high-risk groups distinguished by the model.; Competing Interests: Conflict of interest The authors report no declarations of interest. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Liu, H., et al. (2024). "Clinical efficacy of traditional Chinese medicine therapy for female stress urinary incontinence: a meta-analysis." Revista da Escola de Enfermagem da U S P 57: e20230153.
	OBJECTIVES: To investigate the efficacy of traditional Chinese medicine (TCM) in the treatment of female stress urinary incontinence (SUI). METHOD(S): PubMed, Cochrane, Web of Science, Embase, CNKI, Wanfang, and VIP databases were searched for articles published up to September 2022. Variables were analyzed using weighted mean difference (WMD), standardized mean difference (SMD), odds ratios (OR), and 95% confidence interval (CI). RESULT(S): Eight studies containing 744 patients were included in this study. The results demonstrate that TCM therapy had more advantages in improving the clinical outcome of SUI patients (OR = 2.90, 95%CI:1.92-4.37, P = 0.000), reducing the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score (WMD = -2.41, 95%CI:-2.83- -1.98, P = 0.000), reducing 1-h urinary pad leakage urine volume (WMD = -1.86, 95%CI:-2.23- -1.49, P = 0.000) and increasing Maximum urethral closure pressure (MUCP) (SMD = 0.86, 95%CI: 0.61-1.11, P = 0.000). CONCLUSION(S): TCM therapy is effective in improving urinary incontinence symptoms, urodynamics, and quality of life in patients with SUI. This article provides a reference for the application of TCM therapy in women with urinary incontinence.

Liu, H. F. and N. Yi (2022). "A systematic review and meta-analysis on the efficacy of probiotics for bacterial vaginosis." European Review for Medical and Pharmacological Sciences 26(1): 90-98.
	Objective: The current study aimed at assessing the overall efficacy of probiotics for the treatment of bacterial vaginosis (BV) through the review of relevant studies.; Materials and Methods: A systematic literature review was conducted based largely on the following electronic databases updated to May 2021: Embase, the Cochrane Library, and PubMed, with the use of keywords. The investigators also thoroughly reviewed key pertinent sources in the literature for further inclusion.; Results: Eighteen studies including 1651 patients were selected in the present meta-analysis. In comparison with antibiotics, antibiotics plus probiotics significantly decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months and overall analysis). Compared with placebo, probiotics decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months). Compared with antibiotics, probiotics significantly decreased the recurrence rate of BV (at <1 month, 1-3 months and overall analysis) as well as the incidence of adverse events (AEs) (at less than 1 month) and increased the cure/remission rate of BV (at 1-3 months).; Conclusions: In comparison with short-term probiotics treatment (<1 month), long-term probiotics treatment (1-3 months) yields superior beneficial outcomes and efficacy in the treatment of BV.

Liu, J., et al. (2022). "A phase II, open-label, single-arm study of QL1604 plus paclitaxel-cisplatin/carboplatin as first-line treatment in patients with recurrent or metastatic cervical cancer." Annals of Oncology 33(Supplement 9): S1506.
	Background: Programmed cell death-1 (PD-1) inhibitors have shown efficacy in cervical cancer as monotherapy. QL1604 is a humanized monoclonal antibody against PD-1 and has shown antitumor activity in phase (Ph) I study. Here we report the safety and efficacy results from a Ph II study of QL1604 plus paclitaxel-cisplatin/carboplatin as first-line treatment in patients (pts) with recurrent or metastatic cervical cancer. Method(s): Pts with recurrent or stage IVB cervical cancer not previously treated with systemic chemotherapy were enrolled to receive QL1604 (200 mg)+paclitaxel (175 mg/m2)+cisplatin (70 mg/m2)/carboplatin (AUC 6) at day 1 of each 21-day cycle for up to 6 cycles. Then pts continued to receive QL1604 200 mg Q3W maintenance treatment until disease progression, intolerable toxicity, or other discontinuation events. Primary endpoints were safety endpoints and ORR by investigators per RECIST v1.1 and iRECIST. Result(s): 46 pts were enrolled (squamous cell carcinoma: 41). 39 (84.8%) pts had recurrent disease and 7 (15.2%) pts had stage IVB disease. 38 (82.6%) pts had ECOG PS of 1. As of data cutoff (22 Apr 2022), 97.8% pts experienced TRAEs and 78.3% pts experienced grade (Gr)>=3 TRAEs. The most common TRAEs were white blood cell count decreased (78.3%), neutrophil count decreased (76.1%), and anemia (71.7%). The most common Gr>=3 TRAEs were neutrophil count decreased (47.8%), anemia (32.6%), and white blood cell count decreased (28.3%). 26.1% pts experienced irAEs. 34.8% pts experienced treatment-related SAEs (TRSAEs). ORR and iORR were 58.7% (27/46) and 60.9% (28/46). 6 pts (13.0%) had CR and 21 pts (45.7%) had PR as best response. DCR and iDCR were 84.8% (39/46) and 89.1% (41/46). The median duration of response was 9.6 months (95% CI: 5.5, NE). The median follow-up time for PFS was 6.23 months (range: 0 to 14 months). The median PFS was 8.1 months (95% CI: 5.7, NE). The 12-month PFS rate was 37%. OS was not reached. Conclusion(s): QL1604+paclitaxel+cisplatin/carboplatin showed a manageable safety profile and promising antitumor activity as first-line treatment for pts with recurrent or metastatic cervical cancer. Clinical trial identification: NCT04864782. Legal entity responsible for the study: Qilu Pharmaceutical Co., Ltd. Funding(s): Qilu Pharmaceutical Co., Ltd. Disclosure: X. Zheng, M. Si, B. Zhang, L. Li, X. Kang: Other, Personal, Full or part-time Employment: Qilu Pharmaceutical. All other authors have declared no conflicts of interest.Copyright © 2022

Liu, J., et al. (2021). "Systematic review and meta-analysis of therapeutic effects of pelvic restoration combined with anti-stress urinary incontinence surgery on pelvic floor dysfunction." Annals of Palliative Medicine 10(11): 11678-11687.
	BACKGROUND: In recent years, pelvic restoration surgery is widely used in the diagnosis and treatment of stress urinary incontinence (SUI) as people pay more attention to postpartum pelvic floor dysfunction (PFD). The therapeutic effect of pelvic restoration combined with anti-SUI surgery remains undetermined. The evaluation indicators of the therapeutic effects include the incidence of postoperative obstruction, the incidence of postoperative defecation difficulties, and the quality of life score. METHOD(S): PubMed, Cochrane Library, and EMBASE were searched from the establishment of the database to April 2021 for randomized control trials (RCTs) of pelvic restoration and anti-SUI surgery, and the RevMan5.3 software provided by the Cochrane Collaboration was used for meta-analysis. RESULT(S): A total of 6 documents (a total of 1,944 patients) were included, including 1,021 patients in the experimental group and 923 patients in the control group. The incidence of obstruction after pelvic restoration combined with anti-SUI surgery was statistically significant (OR =1.35, 95% CI, 0.95-1.92, P=0.10); there was a statistically significant difference in the incidence of postoperative dyspareunia (OR =1.58, 95% CI, 0.91-2.74, P=0.10). DISCUSSION: A total of 8 documents included in this meta-analysis confirmed that pelvic restoration combined with anti-SUI surgery for PFD can improve the prognosis and quality of life of patients.

Liu, J., et al. (2022). "Efficacy and safety of QL1706, a novel dual immune checkpoint blockade containing a mixture of anti-PD1 IgG4 and anti-CTLA4 IgG1 antibodies, for advanced cervical cancer: Cohort data from a phase 1b trial." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and anti-programmed cell death 1 (PD-1) antibodies have synergistic effect. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies produced by a single cell line. QL1706 showed promising anti-tumor activity in multiple solid tumors. Here we reported the cervical cancer cohort data from the phase 1b trial of QL1706 (NCT05171790). Method(s): Eligible patients had a pathologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, with recurrent or metastatic, immunotherapy-naive disease at the time of enrollment. Patients were required to have >=one lesion measurable by RECIST v1.1 and disease that had relapsed after a first-line, platinum-based regimen. Patients were included regardless of PD-L1 expression status at baseline. Patients received intravenous QL1706 5.0 mg/kg q3w (i.e., recommended phase 2 dose, defined in a phase 1a trial), for up to 24 months. The primary endpoint was confirmed overall response rate (ORR) per RECIST v1.1 by investigator. The secondary endpoints included disease control rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, etc. Result(s): As of Dec 31, 2021, totally 53 patients with cervical cancer were enrolled (median age, 52 years [range 33-72]). Median follow-up was 5.6 months. Most patients (45 [85%]) had ECOG performance status of 1. Histological breakdown was squamous cell carcinoma (44 [83%]) and adenocarcinoma (nine [17%]). 33 (62%) patients had received one prior chemotherapy, 20(38%) patients had received >=two prior chemotherapy. The confirmed ORR was 28% (95% CI 17%-42%; 15 patients), including one (2%) complete response and 14 (26%) partial response, with median duration of response not reached (95% CI 2.8 months-not estimable). Disease control was observed in 29 (55%; 95% CI 40%-68%) patients. Median PFS was 4.2 months (95% CI 1.7-6.9), and 6-month PFS rate was estimated as 37% (95% CI 24%-51%). Treatment-related adverse events (TRAE) were observed in 40 (75%) patients. Nine (17%) experienced grade >=3 TRAE. The most common TRAE were rash (eight [15%]), hyperthyroidism (eight [15%]), and pyrexia (seven [13%]). Three (6%) patients suffered TRAE leading to dose discontinuation. The immune-related TRAE and serious TRAE were observed in 28 (53%) and eight (15%) patients, respectively. Conclusion(s): QL1706 demonstrated promising and durable clinical activity, with favorable tolerability in patients with recurrent and/or metastatic cervical cancer. Further investigations in this setting are continuing.

Liu, J., et al. (2022). "Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): A systematic review and meta-analysis." Frontiers in Medicine 9: 980511.
	Objective: The aim of this study was to investigate the effect of antibiotic treatment for chronic endometritis (CE) on reproductive outcomes.; Design: Systematic review and meta-analysis.; Patients: Women with reproductive failures, including recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL).; Interventions: Literature searches were performed using three electronic databases (PubMed, Embase, and Web of Science) until 1 December 2021 (without date restriction). The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with normal endometrial histology (negative for CE); and women with cured CE vs. women with persistent CE (PCE). The summary measures were indicated as odds ratio (OR) with a 95% confidence interval (CI).; Main Outcome Measures: These include on-going pregnancy rate/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), and miscarriage rate/pregnancy loss rate (MR/PLR).; Results: A total of 2,154 women (from twelve studies) were enrolled. Compared with the control group, women with CE receiving antibiotics did not show a statistically significant difference in OPR/LBR ( P = 0.09) and CPR ( P = 0.36), although there was a lower MR ( P = 0.03). Women with cured CE have higher OPR/LBR (OR 1.57) and CPR (OR 1.56) in comparison with those with non-CE. There was a statistically significantly higher OPR/LBR (OR 6.82, P < 0.00001) and CPR (OR 9.75, P < 0.00001) in women with cured CE vs. those with persistent CE.; Conclusion: While antibiotic treatment is a sensible option to cure CE, more well-designed prospective studies are needed to evaluate the reproductive impact of antibiotic treatment. Cured CE provides high-quality maternal conditions for subsequent embryo transfer and successful pregnancy.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Liu, Liu, Liu, Cheng and Yan.)

Liu, K., et al. (2022). "Autologous platelet-rich plasma intrauterine perfusion to improve pregnancy outcomes after implantation failure: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 48(12): 3137-3151.
	Aims: Previous studies have reported inconsistent findings on the efficacy of platelet-rich plasma (PRP) therapy in women with implantation failure. The objective of this review was to evaluate whether PRP administration could improve pregnancy outcomes in women with implantation failure undergoing in vitro fertilization.; Methods: Electronic databases were searched for studies that explored the effects of PRP for patients with implantation failure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Based on the available data, we performed subgroup analyses and sensitivity analyses.; Results: Eight studies were included. PRP treatment improved pregnancy outcomes for all women compared with no treatment or placebo (clinical pregnancy rate: OR 2.24, 95% CI 1.41-3.54; live birth rate: OR 5.76, 95% CI 1.55-21.44; miscarriage rate: OR 0.18, 95% CI 0.05-0.63), especially in randomized controlled trials. No significant differences were detected in multiple pregnancy rates (OR 2.54, 95% CI 0.67-9.67). Furthermore, subgroup analysis based on the number of previous implantation failures showed that PRP treatment improved pregnancy outcomes in women with recurrent implantation failure (clinical pregnancy rate: OR 2.55, 95% CI 1.49-4.38; live birth rate: OR 5.07, 95% CI 1.15-22.34; miscarriage rate: OR 0.20, 95% CI 0.05-0.78).; Conclusion: PRP administration could improve pregnancy outcomes in women with recurrent implantation failure. Due to the limited evidence available, the efficacy of PRP in women with recurrent implantation failure needs to be further verified in high-quality studies with larger sample sizes. (© 2022 Japan Society of Obstetrics and Gynecology.)

Liu, K., et al. (2023). "Treatment-related gastrointestinal adverse events of nivolumab plus ipilimumab in randomized clinical trials: a systematic review and meta-analysis." Future Oncology 19(27): 1865-1875.
	The authors used a meta-analysis to evaluate the risks of gastrointestinal adverse events in the cotreatment of malignant tumors with nivolumab and ipilimumab. The meta-analysis revealed that the most common gastrointestinal adverse event at all grades was diarrhea, followed by nausea, decreased appetite, vomiting, constipation, colitis and abdominal pain. The most common severe gastrointestinal adverse events were colitis and diarrhea. Different administration schemes differ in the risk of such events, and thus these events may be minimized by modulating the administration scheme of the cotreatment.Copyright © 2023 Future Medicine Ltd.

Liu, L., et al. (2022). "Traditional Chinese herbal medicine in treating amenorrhea caused by antipsychotic drugs: Meta-analysis and systematic review." Journal of Ethnopharmacology 289: 115044.
	Ethnopharmacological Relevance: Amenorrhea caused by antipsychotic drugs is not uncommon in clinical practice, and various treatment strategies are used to treat the condition. Chinese herbal medicine has its own theory for amenorrhea caused by antipsychotic drugs and has developed its own medication methods.; Aim of the Study: To review and conduct meta-analysis of the use of traditional Chinese herbal medicine in treatment of amenorrhea caused by antipsychotic drugs.; Materials and Methods: A search was conducted across seven Chinese electronic databases (the China National Knowledge Infrastructure (CNKI) database, the China Science and Technology Journal Database, the Wanfang Database, the SinoMed, the Foreign Medical Literature Retrieval Service(FMRS), the Chinese University of Hong Kong Library, the Airiti Library), and the following English databases: MEDLINE, PreMEDLINE, OLD MEDLINE、Publisher Supplied Citation in pubmed; JBI EBP Database, EBM Reviews, Embase, OVID Emcare, Ovid MEDLINE(R), Maternity & Infant Care Database(MIDIRS), APA PsycInfo in OVID, and Cochrane Database of Systematic Reviews (Cochrane Reviews), Database of Abstracts of Reviews of Effects (Other Reviews), Cochrane Central Register of Controlled Trials (Clinical Trials),The Cochrane Methodology Register (Method Studies), Health Technology Assessment Database (Technology Assessments), NHS Economic Evaluation Database (Economic Evaluations) in Cochrane Library; and four databases (Science Direct, ProQuest, Web of Science, and Scopus) in official website using common standards and inclusion/exclusion criteria. The remaining reports were used for preliminary studies. Due to inconsistencies in control groups, randomized controlled trials and articles that combined with other drugs were also excluded. This study is a META analysis of a single rate.; Results: Initial screening returned 912 potentially relevant publications in all databases. After subsequent filtering, a total of 18 articles were included in the analysis. The overall effectiveness for treatment amenorrhea caused by antipsychotic drugs using traditional Chinese herbal medicine was 0.91, with 95% confidence interval of 0.89-0.93. Notably in most studies, the time needed to achieve this level of effectiveness was relatively long, usually in excess of three months. Although a satisfactory verification of an improvement in menstrual cycling takes time, the long treatment duration is a downside. Our analysis revealed that the following Chinese herbal remedies were most common: Danggui (Angelica sinensis (Oliv.) Diels), Chuanxiong (Ligusticum striatum DC.), Taoren (Prunus persica (L.) Batsch), Honghua (Carthamus tinctorius L.), Gancao (Glycyrrhiza uralensis Fisch.), Fuling ((Fungus) Poria cocos (Schw.) Wolf), Baizhu (Atractylodes macrocephala Koidz.), Xiangfu (Cyperus rotundus L.), Chaihu (Bupleurum chinense DC.), Shudihuang (Rehmannia glutinosa (Gaertn.) DC.(Processed), Baishao (Cynanchum otophyllum C.K.Schneid.) CONCLUSIONS: Chinese herbal medicine can effectively treat amenorrhea caused by psychiatric drugs, although it takes a long time to achieve satisfactory effectiveness. More research is needed to better understand different aspects of Chinese herbal medicine use in treatment of this particular medical condition. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Liu, L., et al. (2020). "Effectiveness of tonifying-kidney and regulating-liver therapy on diminished ovarian reserve: a systematic review and Meta-analysis of randomized controlled trials." Journal of Traditional Chinese Medicine 40(3): 343-354.
	OBJECTIVE: To evaluate the effectiveness of the Traditional Chinese Medicine tonifying-kidney and regulating-liver therapy on diminished ovarian reserve (DOR). METHOD(S): The literature was comprehensively searched up to August 2019 using four Chinese and three English electronic databases to extract randomized clinical trials (RCTs) comparing Traditional Chinese Medicine tonifying-kidney and regulating- liver prescriptions (combined with hormone therapy or not) with Western Medicine. Data quality evaluation was conducted using the Cochrane risk of bias tool. Meta-analysis was conducted using Revman 5.3 software with effect estimates presented as mean difference (MD), risk ratio (RR), and 95% confidence interval (CI). RESULT(S): A total of nine RCTs with 512 participants were extracted and eligible for Meta-analysis. There were no significant differences between Chinese medicine and Western Medicine on basal serum follicle-stimulating hormone (FSH) level (MD 0.11, 95% CI -0.52 to 0.74, 392 participants, seven trials), anti-Mullerian hormone level (MD 0.48, 95% CI - 0.62 to 1.58, 95 participants, two trials), and the FSH and luteinizing hormone ratio (MD 0.01, 95% CI -0.95 to 0.96, 115 participants, two trials). Chinese medicine was more effective at improving Traditional Chinese Medicine symptom scores (TCMSS) (MD -2.39, 95% CI -3.83 to -0.94, 160 participants, three trials), effective rate of TCMSS (RR 1.18, 95% CI 1.02 to 1.36, 160 participants, three trials), antral follicle count (AFC) (MD 0.55, 95% CI 0.05 to 1.04, 155 participants, three trials), and FSH levels at 3 months post-treatment (MD - 4.77, 95% CI -6.09 to -3.45, 137 participants, two trials). CONCLUSION(S): Compared with Western Medicine, tonifying-kidney and regulating-liver therapy is more effective at relieving symptoms and improving AFC and FSH at 3 months post-treatment.Copyright © 2020 JTCM. All rights reserved.

Liu, L., et al. (2021). "Image-guided thermal ablation in the management of symptomatic adenomyosis: a systematic review and meta-analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 38(1): 948-962.
	Objective: To evaluate the clinical effects of image-guided thermal ablation for the treatment of symptomatic adenomyosis (AD).; Data Sources: We searched PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov and Google Scholar for literature from January 2000 to September 2020.; Methods of Study Selection: We included all studies reporting clinical outcomes of image-guided thermal ablation for AD, involving high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA) and radiofrequency ablation (RFA). Two independent researchers performed study selection according to the screening criteria.; Results: A total of 38 studies representing 15,908 women were included. Compared with those at baseline, the visual analog scale scores, the symptom severity scores and the menorrhagia severity scores decreased significantly after these thermal ablation therapies. The mean ablation time was 92.18 min, 24.15 min and 31.93 min during HIFU, PMWA and RFA, respectively. The non-perfused volume ratio of AD was 68.3% for HIFU, 82.5% for PMWA and 79.2% for RFA. The reduction rates of uterine volume were 33.6% (HIFU), 46.8% (PMWA) and 44.0% (RFA). The reduction rates of AD volume were 45.1% (HIFU), 74.9% (PMWA) and 61.3% (RFA). The relief rates of dysmenorrhea were 84.2% (HIFU), 89.7% (PMWA) and 89.2% (RFA). The incidence of minor adverse events was 39.0% (HIFU), 51.3% (PMWA) and 3.6% (RFA). The re-intervention rates were 4.0% (HIFU) and 28.7% (RFA). The recurrence rate was 10.2% after HIFU. The pregnancy rates were 16.7% (HIFU), 4.93% (PMWA) and 35.8% (RFA).; Conclusion: Image-guided HIFU, PMWA and RFA may be effective and safe minimally invasive therapies for symptomatic AD.

Liu, L., et al. (2021). "Ultrasound-guided Microwave Ablation in the Management of Symptomatic Uterine Myomas: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(12): 1982-1992.
	Objective: This systematic review and meta-analysis aimed to evaluate the clinical effects and safety of ultrasound-guided microwave ablation (MWA) for the treatment of symptomatic uterine myomas.; Data Sources: We searched PubMed, Web of Science Core Collection, Cochrane Library, Embase, Scopus, and Google Scholar for studies from January 2000 to January 2021.; Methods of Study Selection: We included all studies that reported the clinical outcomes of ultrasound-guided MWA in women with symptomatic uterine myomas. Two researchers conducted the study selection according to the screening criteria.; Tabulation, Integration, and Results: We evaluated the risk of bias and evidence quality using the Newcastle-Ottawa scale. Two researchers independently extracted information from the included studies. We extracted the standardized mean difference (SMD) and pooled proportion with a 95% confidence interval (CI) for the outcome measures of interest. A total of 10 studies representing 671 patients were included. The Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire was used to assess the clinical effects. Compared with baseline, the UFS scores decreased significantly (SMD 3.37; 95% CI, 2.27-4.47; p <.001; reduction rate 65.9%), QoL scores increased significantly (SMD -3.12; 95% CI, -3.93 to -2.30; p <.001; rate of increase 72.0%), and hemoglobin concentration increased significantly (SMD -2.13; 95% CI, -3.44 to -0.81; p = .002; rate of increase 30.3%) at follow-up. The mean operation time was 34.48 minutes (95% CI, 22.82-46.13; p <.001). The rate of reduction in myoma volume after MWA was 85.3% (95% CI, 82.7%-88.0%, p <.001). No major adverse event was reported, and the incidence of minor adverse events was 21.1% (95% CI, 15.1%-27.0%, p <.001).; Conclusion: Ultrasound-guided MWA is an effective and safe minimally invasive therapy for symptomatic uterine myomas. (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Liu, L., et al. (2021). "Uterine Artery Embolization Compared with High-intensity Focused Ultrasound Ablation for the Treatment of Symptomatic Uterine Myomas: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(2): 218-227.
	Objective: This study aimed to compare the clinical effects of uterine artery embolization (UAE) with those of high-intensity focused ultrasound (HIFU) ablation for the treatment of symptomatic uterine myomas.; Data Sources: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrials.gov for studies from January 2000 to August 2020. Related articles and relevant references of the included studies were also searched.; Methods of Study Selection: Two researchers independently performed the data selection. We included comparative studies that compared the clinical outcomes of UAE with those of HIFU ablation in women with myomas.; Tabulation, Integration, and Results: We assessed the study quality using the Cochrane Handbook for Systematic Reviews of Interventions for evaluating the risk of bias. Two independent researchers performed the article selection according to the screening criteria and rated the quality of evidence for each article. We calculated pooled mean difference with 95% confidence interval (CI) for continuous data and relative risk (RR) with 95% CI for dichotomous data. The systematic review registration number is CRD42020199630 on the International Prospective Register of Systematic Reviews. A total of 7 articles (5 trials), involving 4592 women with symptomatic uterine myomas, were included in the meta-analysis. Compared with the HIFU ablation group, the decrease in "uterine fibroid symptom" scores as well as the increase in quality-of-life scores at the time of follow-up were higher in the UAE group, with overall mean difference 19.54 (95% CI, 15.21-23.87; p <.001) and 15.72 (95% CI, 8.30-23.13; p <.001), respectively. The women in the UAE group had a significantly lower reintervention rate (RR 0.25; 95% CI, 0.15-0.42; p <.001). The women undergoing UAE had a significantly lower pregnancy rate than those undergoing HIFU ablation (RR 0.06; 95% CI, 0.01-0.45; p = .006). The difference in the incidence of adverse events between the 2 groups was not statistically significant (p = .53).; Conclusion: Compared with HIFU ablation, UAE provided more significant alleviation of symptoms and improvement in quality of life, lower postoperative reintervention rate, and lower pregnancy rate for women with uterine myomas. However, we cannot conclude that HIFU ablation is more favorable for desired pregnancy than UAE because of the confounding factors. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Liu, L., et al. (2022). "High-intensity focused ultrasound (HIFU) ablation versus surgical interventions for the treatment of symptomatic uterine fibroids: a meta-analysis." European radiology 32(2): 1195-1204.
	Objectives: To compare the treatment success and safety of ultrasound- and MR-guided high-intensity focused ultrasound (HIFU) with surgery for treating symptomatic uterine fibroids.; Methods: We searched studies comparing HIFU with surgery for fibroids in different databases from January 2000 to July 2020. The mean difference (MD) or relative risk (RR) with 95% confidence interval (CI) for different outcome parameters was synthesized.; Results: We included 10 studies involving 4450 women. Compared with the surgery group, the decrease in uterine fibroid severity score at 6- and 12-month follow-up was higher in the HIFU group (MD - 4.16, 95% CI - 7.39 to - 0.94, and MD - 2.44, 95% CI - 3.67 to - 1.20, p < 0.05). The increase in quality-of-life (QoL) score at 6- and 12-month follow-up was higher in the HIFU group (MD 2.13, 95% CI 0.86 to 3.14, and MD 2.34, 95% CI 0.82 to 3.85, p < 0.05). The duration of hospital stay and the time to return to work was shorter in the HIFU group (MD - 3.41 days, 95% CI - 5.11 to - 1.70, and MD - 11.61 days, 95% CI - 19.73 to - 3.50, p < 0.05). The incidence of significant complications was lower in the HIFU group (RR 0.33, 95% CI 0.13 to 0.81, p < 0.05). The differences in the outcomes of adverse events, symptom recurrence, re-intervention, and pregnancy were not statistically significant (p > 0.05).; Conclusions: HIFU is superior to surgery in terms of symptomatic relief, improvement in QoL, recovery, and significant complications. However, HIFU showed comparable effects to surgery regarding the incidence of adverse events, symptom recurrence, re-intervention, and pregnancy.; Key Points: • HIFU ablation is superior to surgery in terms of symptomatic relief, improvement in QoL, recovery, and significant complications. • HIFU has comparable effects to surgery in terms of symptom recurrence rate, re-intervention rate, and pregnancy rate, indicating that HIFU is a promising non-invasive therapy that seems not to raise the risk of recurrence and re-intervention or deteriorate fertility compared to surgical approaches in women with fibroids. • There is still a lack of good-quality comparative data and further randomized studies are necessary to provide sufficient and reliable data, especially on re-intervention rate and pregnancy outcome. (© 2021. European Society of Radiology.)

Liu, M., et al. (2022). "Efficacy of CO 2 laser treatment in postmenopausal women with vulvovaginal atrophy: A meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 158(2): 241-251.
	Objective: To explore the efficacy of CO 2 laser treatment in postmenopausal women with vulvovaginal atrophy.; Method: PubMed, Embase, Cochrane Library and Web of Science were searched to June 9, 2020. Prospective studies on the efficacy of CO 2 laser treatment were included. Two researchers independently reviewed articles and extracted data. Heterogeneity test was conducted for each outcome indicator. Sensitivity analysis was performed in all models.; Results: Twelve articles including 459 participants were enrolled. Compared with baseline, vaginal health indeices (VHIs) were significantly higher at the 1-, 3-, 6-, and 12-month follow ups (P < 0.001). For VVA severity, the visual analog scale scores for vaginal dryness at 1-, 3-, 6-, and 12-month follow-ups (P < 0.050), vaginal burning, itching, and dysuria at 1-month follow up (P < 0.001), and dyspareunia at 1-, 3-, 6-, and 12-month follow-ups (P < 0.001) were all significantly lower. For FSFI, total scores at 1-, 3-, 6-, and 12-month follow ups (P < 0.001), and the scores in desire, arousal, lubrication, orgasm, satisfaction, and pain at 1-month follow up (P < 0.050) were all significantly higher. For quality of life, the PCS12 and MCS12 scores were all significantly higher (P < 0.050) at the 1-month follow up.; Conclusion: CO 2 laser treatment may be effective for postmenopausal women with VVA symptoms in improving quality of life and sexual function. (© 2021 International Federation of Gynecology and Obstetrics.)

Liu, M., et al. (2022). "The effectiveness of immunomodulatory therapies for patients with repeated implantation failure: a systematic review and network meta-analysis." Scientific Reports 12(1): 18434.
	This meta-analysis analyzed the clinical pregnancy outcomes of repeated implantation failure (RIF) patients treated with immunomodulatory therapies. Publications (published by August 16, 2021) were identified by searching the PubMed, Embase, and Web of Science databases. The quality of the studies was evaluated with the Cochrane bias risk assessment tool, and a network meta-analysis was performed with Stata 14.0. The outcomes were clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). The results of our network meta-analysis of 16 RCTs (including 2,008 participants) show that PBMCs, PRP, and SC-GCSF can significantly improve the CPR compared with LMWH (PBMCs: OR 2.15; 95% CI 1.21-3.83; PRP: OR 2.38; 95% CI 1.08-5.24; SC-GCSF: OR 2.46; 95% CI 1.05-5.72). The LBR of PRP was significantly higher than those of IU-GCSF (OR 3.81; 95% CI 1.22-11.86), LMWH (OR 4.38; 95% CI 1.50-12.90), and intralipid (OR 3.85; 95% CI 1.03-14.29), and the LBR of PBMCs was also significantly better than that of LMWH (OR 2.35; 95% CI 1.14-4.85). Furthermore, PRP treatment significantly improved the IR compared with LMWH treatment (OR 2.81; 95% CI 1.07-7.4). The limited evidence from existing RCTs suggests that PBMCs and PRP are the best therapeutic options for RIF patients. However, owing to the quantity limitation, more top-quality research is required to obtain additional high-level evidence.Copyright © 2022. The Author(s).

Liu, M., et al. (2020). "Efficacy of coenzyme Q10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with polycystic ovary syndrome: A protocol for a systematic review and meta-analysis." Medicine 99(46): e23130.
	Background: Polycystic ovary syndrome (PCOS) is one of the common gynecological endocrine system diseases. It is characterized by excessive androgen, rare or anovulation, and polycystic ovary morphology. Coenzyme Q10 (CoQ10) is a fat-soluble natural vitamin, which has a continuous oxidation-reduction cycle and is an effective antioxidant that can protect ovaries from oxidative damage. This study aims to systematically summarize and analyze the scientific literatures on glucose metabolism index, lipid profiles, inflammatory factor, and sex hormone level of PCOS patients treated with CoQ10 to provide a reference basis for clinical treatment.; Methods: We will retrieve the following electronic databases from the built-in until March 2021: Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Clinical Trials. gov, Chinese Scientific Journal Database (VIP), and Wang-fang database. Two reviewers will independently scan the articles searched, de-duplication, filtering, quality assessment. Differences will be resolved by discussion between the 2 reviewers or by a third reviewers. All analyses were systematic to evaluate interventions based on the Cochrane handbook. Meta-analysis and/or subgroup analysis will be performed on the basis of the included studies.; Discussion: This review will be to investigate the efficacy of CoQ10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with PCOS and provide a high-quality synthesis to assess whether CoQ10 is an effective and safe intervention for PCOS. The results of the analysis will be published in a scientific journal after peer-review.; Systematic Review Registration: INPLASY 2020100013.

Liu, M., et al. (2020). "Efficacy of different forms of Guizhi Fuling Wan on reproduction and metabolism in women with polycystic ovary syndrome: A protocol for a meta-analysis of randomized controlled trials." Medicine 99(44): e22954.
	Background: Polycystic ovary syndrome (PCOS), is a common endocrine disorder in women characterized by increased androgen levels, ovulatory dysfunction, and polycystic ovaries. Western medicine is widely used for the treatment of PCOS, but patient satisfaction is low, largely due to its associated gastrointestinal symptoms of nausea and diarrhea. Guizhi Fuling Wan (GFW) is a traditional Chinese medicine used to remove blood stasis and dissipate phlegm for treating gynecological diseases that was invented by Zhang Zhongjing in the Eastern Han dynasty. In recent years, GFW has been widely used to treat patients with PCOS. This study aims to assess the efficacy and safety of GFW in the treatment of PCOS through a systematic review and meta-analysis.; Methods: All randomized controlled trials connected with GFW targeting PCOS will be searched in the following electronic bibliographic databases from their earliest recorded publications to December 2020 without any language restrictions: MEDLINE, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biological Medicine Database, Wan-fang data, Chinese Technical Periodicals, and other databases. The primary outcomes include Sex hormone levels, ovulation rate, pregnancy rate, and total effective rate. The secondary outcomes were Total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, fasting glucose, fasting insulin, insulin sensitivity index, body mass index, hypertrichosis score, acne score, adverse reactions, etc. Two reviewers will independently conduct cations retrieval, de-duplication, filtering, quality assessment, and data analysis by Endnote X9.1 and Review Manager software (RevMan V.5.3). Meta-analysis and/or subgroup analysis will be performed on the included data.; Discussion: This study will investigate the application of GFW in the treatment or prevention of PCOS, and provide a high-quality synthesis to judge whether GFW is an effective and safe intervention for PCOS.; Prospero Registration Number: CRD42020192405.

Liu, N. and G. Ray Joel (2023). "Short-Term Adverse Outcomes After Mifepristone-Misoprostol Versus Procedural Induced Abortion : A Population-Based Propensity-Weighted Study." Annals of Internal Medicine 176(2): 145-153.
	Background: Prior studies comparing first-trimester pharmaceutical induced abortion (IA) with procedural IA were prone to selection bias, were underpowered to assess serious adverse events (SAEs), and did not account for confounding by indication. Starting in 2017, mifepristone-misoprostol was dispensed at no cost in outpatient pharmacies across Ontario, Canada.; Objective: To compare short-term risk for adverse outcomes after early IA by mifepristone-misoprostol versus by procedural IA.; Design: Population-based cohort study.; Setting: Ontario, Canada.; Patients: All women who had first-trimester IA.; Measurements: A total of 39 856 women dispensed mifepristone-misoprostol as outpatients were compared with 65 176 women undergoing procedural IA at 14 weeks' gestation or earlier within nonhospital outpatient clinics (comparison 1). A total of 39 856 women prescribed mifepristone-misoprostol were compared with 8861 women undergoing ambulatory hospital-based procedural IA at an estimated 9 weeks' gestation or less (comparison 2). The primary composite outcome was any SAE within 42 days after IA, including severe maternal morbidity, end-organ damage, intensive care unit admission, or death. A coprimary broader outcome comprised any SAE, hemorrhage, retained products of conception, infection, or transfusion. Stabilized inverse probability of treatment weighting accounted for confounding between exposure groups.; Results: Mean age at IA was about 29 years (SD, 7); 33% were primigravidae. Six percent resided in rural areas, and 25% resided in low-income neighborhoods. In comparison 1, SAEs occurred among 133 women after mifepristone-misoprostol IA (3.3 per 1000) versus 114 after procedural IA (1.8 per 1000) (relative risk [RR], 1.87 [95% CI, 1.44 to 2.43]; absolute risk difference [ARD], 1.5 per 1000 [CI, 0.9 to 2.2]). The respective rates of any adverse event were 28.9 versus 12.4 per 1000 (RR, 2.33 [CI, 2.11 to 2.57]; ARD, 16.5 per 1000 [CI, 14.5 to 18.4]). In comparison 2, SAEs occurred among 133 (3.4 per 1000) and 27 (3.3 per 1000) women, respectively (RR, 1.04 [CI, 0.61 to 1.78]). The respective rates of any adverse event were 31.2 versus 24.9 per 1000 (RR, 1.25 [CI, 1.04 to 1.51]).; Limitation: A woman prescribed mifepristone-misoprostol may not have taken the medication, and the exact gestational age at IA was not always known.; Conclusion: Although rare, short-term adverse events are more likely after mifepristone-misoprostol IA than procedural IA, especially for less serious adverse outcomes.; Primary Funding Source: Canadian Institutes of Health Research.

Liu, S., et al. (2021). "The use of bevacizumab in the modern era of targeted therapy for ovarian cancer: A systematic review and meta-analysis." Gynecologic Oncology 161(2): 601-612.
	Objectives: The optimal systemic therapy strategy for advanced epithelial ovarian cancer (EOC) remains unclear. We performed a systematic review and meta-analysis to assess oncologic outcomes and toxicity of bevacizumab combination treatment in advanced EOC.; Methods: We conducted an electronic search of all phase 2 and 3 clinical trials involving bevacizumab combination therapy in advanced-stage EOC between 2010 and March 2020, using Embase, Medline, Epub Ahead of Print, Cochrane for clinical trials, Cochrane Database of Systematic Reviews, Web of Science and clinicaltrials.gov databases. Progression-free survival (PFS), overall survival (OS), and their hazard ratios (HR) when available were extracted. Pooled HR were calculated for each efficacy endpoint in the meta-analysis using inverse variance weighted method. Bias was assessed using the Cochrane Collaboration Risk of Bias I (ROB1) tool for randomized controlled trials.; Results: Thirty-five studies were included in the qualitative analysis and eight studies in the quantitative synthesis. In the first-line setting, bevacizumab combined with chemotherapy revealed a significant improvement in PFS (pooled HR = 0.72, 95% CI 0.65-0.81) when compared to chemotherapy alone but no significant OS benefit (pooled HR = 0.88, 95% CI 0.72-1.06). In the recurrent setting, bevacizumab combinations showed significant PFS (pooled HR = 0.52, 95% CI 0.47-0.58) and OS benefits (pooled HR = 0.88, 95% CI 0.79-0.99) compared with non-bevacizumab regimens. Rate of bowel perforation was low at 1.24% (range 0-4.2%).; Conclusions: Bevacizumab-containing regimens are associated with significant PFS benefit in advanced and recurrent epithelial ovarian cancer. While the difference in OS did not reach statistical significance in the first-line setting, bevacizumab was associated with improved survival in the recurrent setting.; Competing Interests: Declaration of Competing Interest The authors have no personal nor financial conflict of interests to disclose. Several of the clinical trials included in this systematic review were conducted at the Princess Margaret Cancer Centre. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Liu Shiru, L., et al. (2022). "Patterns of First-Line Systemic Therapy Delivery and Outcomes in Advanced Epithelial Ovarian Cancer in Ontario." Current oncology (Toronto, Ont.) 29(8): 5988-6009.
	Background: First-line treatment of epithelial ovarian cancer (EOC) consists of a combination of cytoreductive surgery and platinum-based chemotherapy. Recently, targeted therapies such as bevacizumab have been shown to improve oncologic outcomes in a subset of a high-risk population. The objective of this study is to evaluate the patterns of practice and outcomes of first-line systemic treatment of advanced EOC, focusing on the adoption of bevacizumab.; Methods: A population cohort study was conducted using administrative data in Ontario, Canada. Patients diagnosed with advanced stage non-mucinous EOC between 2014 and 2018 were identified. Datasets were linked to obtaining information on first-line treatment including surgery, systemic therapy, providers of care, systemic therapy facilities, and acute care utilization (emergency department (ED) visits and hospitalizations) during systemic treatment. Multivariate logistic regression was used to determine factors associated with systemic therapy utilization.; Results: Among 3726 patients with advanced EOC, 2838 (76%) received chemotherapy: 1316 (47%) received neoadjuvant chemotherapy, 1060 (37%) underwent primary cytoreductive surgery followed by chemotherapy, and 462 (16%) received chemotherapy only. The median age was 67 (range: 20-100). Most chemotherapies were prescribed by gynecologic oncologists (60%) and in level 1 academic cancer centres (58%). Only 54 patients (3.1%) received bevacizumab in the first-line setting after its approval in Ontario in 2016. Bevacizumab was more likely to be administered by medical oncologists compared to gynecologic oncologists (OR 3.95, 95% CI 2.11-7.14). In total, 1561 (55%) and 1594 (56%) patients had at least one ED visit and/or hospitalization during systemic treatment, respectively. The most common reasons for ED visits were fever and bowel obstruction.; Conclusion: Patterns of care for EOC in Ontario differed between care providers. The uptake of bevacizumab for first-line treatment of EOC was low. Acute care utilization related to EOC was high.

Liu, S. M. and R. Flink-Bochacki (2021). "A single-blinded randomized controlled trial evaluating pain and opioid use after dilator placement for second-trimester abortion." Contraception 103(3): 171‐177.
	OBJECTIVES: To compare pain levels and medication needs after placement of laminaria vs Dilapan‐S, and after dilation and evacuation (D&E). STUDY DESIGN: We conducted a single‐blinded randomized control trial of patients undergoing D&E at 15 0/7 to 23 6/7 weeks gestation, randomizing to cervical preparation with laminaria or Dilapan‐S. We compared pain levels and medication usage following dilator placement (5 minutes; 2, 4, and 8 hours; the following morning) and D&E (1, 4, 24, and 48 hours). Our primary outcome was median change from baseline pain, and secondary outcomes included maximum pain timing and overall narcotic use. We compared baseline characteristics, median pain increases and quantities of narcotics used. RESULTS: We analyzed 67 participants with laminaria (n = 34) and Dilapan‐S (n = 33). More Dilapan‐S users had a prior vaginal delivery (n = 20, 60.6%) than laminaria users (n = 11, 32.4%), p = 0.02. Maximum median pain was not statistically different (Laminaria: +3.5 (interquartile range [IQR] +0.5, +6.5); Dilapan‐S: +3 (IQR +1, +5); p = 0.42. Thirty‐seven (63.8%) participants reported higher levels of pain following dilator placement than D&E. Overall, 26 (42.6%) participants used narcotics during their abortion episode, with no difference in median number of tablets between laminaria (2, range 1‐8) and Dilapan‐S (4.5, range 1‐15) participants (p = 0.34). CONCLUSIONS: Median pain increase did not differ in participants receiving laminaria or Dilapan‐S for cervical preparation prior to D&E. The majority of patients will use a small amount of narcotics if available. IMPLICATIONS: The lack of difference in pain between laminaria and Dilapan‐S enhances the applicability of pain intervention research across dilator types. With over half of participants using a small amount of narcotics during their D&E episode, pain management should be individualized to patient needs.

Liu, T., et al. (2019). "Acupuncture for uterine fibroids: Protocol for a systematic review of randomized controlled trials." Medicine 98(8): e14631.
	Background: Uterine fibroids represent the most common gynecological benign tumors in reproductive females. Acupuncture has been applied as a therapeutic modality in China to treat uterine fibroids. However, currently, few critical systematic reviews regarding the effect of acupuncture on uterine fibroids have been published. Our proposed review aims to evaluate the current evidence on the efficacy of acupuncture for uterine fibroids.; Methods: A total of 7 databases were searched from their inception to December 2018, including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure database, the Chinese Biomedical database, and the Wanfang database. The primary outcomes will be reduction in uterine volume and number of fibroids. Secondary outcomes are pelvic or low-back pain, assessed by Visual Analog Scale (VAS); Irregular menstrual periods; Low-abdominal pressure symptoms such as frequent or urgent urination, or constipation and adverse events. Data synthesis will be computed by RevManV.5.3.5 software when a data-analysis is allowed. Methodological quality will be evaluated with the risk of bias according to Cochrane Handbook.; Results: This study will provide high-quality evidence of acupuncture for uterine fibroids.; Conclusion: The conclusion of this systematic review will provide evidence to judge whether acupuncture is an effective therapeutic intervention for patients with uterine fibroids.; Trial Registration Number: PROSPERO CRD42019120484.

Liu, W., et al. (2019). "Kuntai Capsule plus Hormone Therapy vs. Hormone Therapy Alone in Patients with Premature Ovarian Failure: A Systematic Review and Meta-Analysis." Evidence-based Complementary and Alternative Medicine 2019: 2085804.
	The aim of this study was to evaluate the efficacy and safety of Kuntai capsules (KTC) plus hormone therapy (HT) compared to HT alone for the treatment of premature ovarian failure (POF). Databases including PubMed, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), and the Wanfang database were searched up to October 2018 for randomized controlled trials (RCTs). After screening the studies, extracting the data, and assessing the study quality, Cochrane RevMan 5.3 software was used to conduct a meta-analysis. Twelve RCTs involving 1178 patients were included. Regarding the therapeutic effects, total effective treatment rate was higher for the KTC+HT groups compared to the HT-only groups. Furthermore, compared with HT, KTC+HR effectively altered endocrine indexes involving serum levels of luteinizing hormone (weighted mean difference [WMD]=-3.47, 95% CI [5.68, -1.26], P=0.002]), follicle-stimulating hormone [WMD=-8.15, 95% CI [-10.44, -5.86], P<0.00001], estrogen [WMD=17.21, 95% CI [10.16, 24.26], P<0.00001], and anti-Mullerian hormone [WMD=1.07, 95% CI [0.78, 1.36], P<0.00001]; blood lipid indexes involving serum levels of triglyceride (WMD=-0.55, 95% CI [-0.76, -0.43], P<0.00001), total cholesterol (WMD=-0.63, 95% CI [-0.74, -0.52], P<0.00001), and low-density lipoprotein cholesterol (WMD=-0.62, 95% CI [-0.75, -0.49], P<0.00001); and B-ultrasound results involving ovarian resistance index (WMD=-0.20, 95% CI [-0.35, -0.04], P=0.01), perfusion index (WMD=-0.41, 95% CI [-0.57, -0.24], P<0.00001), peak systolic velocity (WMD=2.43, 95% CI [1.52, 3.34], P<0.00001), antral follicle count (WMD=1.20, 95% CI [0.41, 2.00], P=0.003), and mean ovarian diameter in the plane containing the longest axis of the ovary (WMD=4.34, 95% CI [2.94, 5.74], P<0.00001). There were no serious adverse events in either group. There is evidence that KTC+HT is more effective and safer than HT alone for treating POF. However, the trials had low methodological quality and small samples, so further standardized research is required.Copyright © 2019 Weiping Liu et al.

Liu, W., et al. (2022). "Efficacy and Safety of Acupuncture and or Moxibustion for Managing Primary Dysmenorrhea: A Systematic Review and Meta-Analysis." Clinical nursing research 31(7): 1362-1375.
	Acupuncture and moxibustion have been accepted as add-on options for primary dysmenorrhea (PD); however, the clinical evidence is still inadequate. We searched AMED, CENTRAL, EMBASE, PubMed, Web of Science, CBM, CNKI, VIP, Wangfang database, ANZCTR, ClinicalTrials.gov, and the WHO ICTRP, from their inception to February 2021. The pooled analysis of 13 RCTs with 675 participants for VAS showed that acupuncture and moxibustion were more effective in managing PD than the control group with the MD of -1.93 (95% CI [-2.80, -1.06] and -2.67 (95% CI [-4.96, -0.38]). With the CMSS, seven studies with 487 participants showed that these modalities were more effective than the control group with the MD of -7.58 (95% CI [-10.97, -4.19]) and -3.78 (95% CI [-6.90, -0.66]). The findings indicated that acupuncture and moxibustion could relieve pain effectively and has fewer adverse events (AEs) in managing PD.

Liu, W.-J., et al. (2022). "New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis." Reproductive Biomedicine Online 45(6): 1167-1175.
	Research Question: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes?; Design: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared.; Results: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates.; Conclusions: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Liu, X., et al. (2022). "Human umbilical cord mesenchymal stem cells in endometrial injury repair." Chinese Journal of Tissue Engineering Research 26(24): 3921-3927.
	BACKGROUND: Human umbilical cord mesenchymal stem cells have the characteristics of strong differentiation and immunoregulation, which have been widely concerned in cell therapy. OBJECTIVE(S): To summarize the research progress of human umbilical cord mesenchymal stem cells in the treatment of endometrial related diseases. METHOD(S): Key words were "human umbilical cord mesenchymal stem cells, endometrium, endometriosis, intrauterine adhesions, thin endometrium" in Chinese and English. PubMed, CNKI, and Wanfang databases were retrieved for articles published from 1991 to 2020. Totally 64 articles meeting the inclusion criteria were reviewed and analyzed. RESULTS AND CONCLUSION(S): (1) Human umbilical cord mesenchymal stem cells, as a kind of stem cells with considerable development potential, have the advantages of rich sources, convenient collection, significant cell proliferation and differentiation. (2) Human umbilical cord mesenchymal stem cells promote the repair of endometrial cell injury, reduce scar formation and improve endometrial function through immune regulation, cell differentiation and down-regulation of fibrotic gene expression, which is conducive to embryo implantation and pregnancy. (3) The important mechanism of human umbilical cord mesenchymal stem cell transplantation for endometrium may be related to their paracrine cytokines and nutritional factors, and these factors participate in endometrial repair and immune regulation. (4) The treatment method based on human umbilical cord mesenchymal stem cells has achieved some promising results in the treatment of endometrial injury diseases, such as inhibiting the proliferation and promoting the apoptosis of endometrial cells in vitro, and restoring the fertility of endometriosis rats by repairing the damaged endometrium. It can remarkably promote the regenerative repair of endometrium in rats with severe intrauterine adhesion syndrome, promote vascular regeneration, restore endometrial function, increase the thickness of endometrium through immune regulation, improve endometrial receptivity, and provide new ideas for the treatment of thin endometrium. (5) Human umbilical cord mesenchymal stem cells can escape the recognition of the body's immune system and avoid host monitoring, so infusion into the body will not cause strong rejection. (6) At present, most of the research is still limited to animal experiments, and its application in clinical treatment is not extensive. In the future, more clinical trials are needed to further study treatment mechanism of human umbilical cord mesenchymal stem cells for endometrium.Copyright © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.

Liu, X., et al. (2020). "Effects of acupuncture on Luteinized Unruptured Follicle Syndrome: A meta-analysis of randomized controlled trials." Complementary Therapies in Medicine 49: 102319.
	Purpose: This meta-analysis aimed to evaluate the comprehensive efficiency and safety of acupuncture on Luteinized Unruptured Follicle Syndrome based on Randomized Controlled Trials (RCTs).; Methods: Six electronic databases (i.e. Wanfang, VIP, China National Knowledge Infrastructure, Pubmed, Cochrane, and Embase) were searched from inception to July 2019. Randomized controlled trials were eligible to evaluate the effects of acupuncture alone or acupuncture as an adjunct. The primary outcomes were the ovulation rate and pregnancy rate. Two reviewers proceeded study selection and quality assessment of included trials and performed heterogeneity of included studies before meta-analysis.Trial Sequential Analysis was used to assess the risk of random error and estimate required information size. The Grading of Recommendations Assessment, Development and Evaluation was applied for assessing level of evidence.; Results: 10 studies involving 715 participants were included Meta-analysis showed acupuncture alone and acupuncture as an adjunct both could significantly improve ovulation, which were confirmed by Trial Sequential Analysis. The evidence of acupuncture improving pregnancy rate was insufficient. Improved serum luteinizing hormone and estradiol levels, and decreased pulsatility index and resistance index of ovary artery were shown in both two subgroups. Level of evidence of most outcomes was "low" or "very low", so the results should be cautiously interpreted.; Conclusions: Acupuncture alone or be combined with drugs are effective on Luteinized Unruptured Follicle Syndrome especially for improving ovulation . While concurrent evidence is insufficient, and further studies of high quality are needed to strengthen the conclusion.; Competing Interests: Declaration of Competing Interest There is no interest competition among authors. (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Liu, X., et al. (2022). "Physical exercise interventions for perinatal depression symptoms in women: A systematic review and meta-analysis." Frontiers in psychology 13: 1022402.
	BACKGROUND: The previous meta-analysis indicated that physical exercise could play a crucially therapeutic role in reducing perinatal depression symptoms in women. However, the efficacy varies across different exercise types, forms, intensities, and duration. AIM: The purpose of this study was to review and evaluate the effects of different types, forms, intensities, and duration of exercise for improving perinatal depressive symptoms. DESIGN: A systematic review and meta-analysis. METHODS: Randomized controlled trials until December 2021 were searched from seven databases, including PubMed, EMBASE, Medline, CINAHL, Web of Science, Cochrane Library, and PsycINFO. The risk of bias in eligible trials was evaluated using the Cochrane Risk of Bias tool. When high heterogeneity was tested, we used random-effects models. A funnel plot was used to assess the publication bias. This review was performed under the PRISMA guidelines, Consensus on Exercise Reporting (CERT) checklist and Cochrane Handbook. The certainty of the body of evidence was assessed using the GRADE method. RESULTS: Of 1,573 records, 20 trials were identified in this study. The results of this review revealed that women with perinatal depression symptoms gained benefits from physical exercise [OR = 0.62, 95% CI (0.45, 0.86), P = 0.004; MD = -0.57, 95% CI (-0.83, -0.30), P < 0.0001]. Type of walking [SMD = -1.06, 95% CI (-1.92, -0.19), P < 0.00001], form of "Individual + group-based"exercise [SMD = -0.91, 95% CI (-0.80, -0.03), P = 0.04], intensity of ≥150 min per week [SMD = -0.84, 95% CI (-1.53, -0.15), P = 0.02], and ≥12 weeks duration [SMD = -0.53, 95% CI (-0.75, -0.31), P < 0.00001] seemed to generate more prominent improvement on perinatal depression symptoms. CONCLUSION: Physical exercise showed a significant effect on reducing perinatal depressive symptoms. This meta-analysis provides an important update on exercise's efficacy in treating perinatal depression. Further higher quality and large-scale trials are needed to substantiate our findings. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296230].

Liu, X., et al. (2022). "522MO Preliminary results of sintilimab (Sin)+bevacizumab (Bev) in recurrent/persistent ovarian clear cell carcinoma (INOVA): A multicenter, single-arm, phase II trial." Annals of Oncology 33(Supplement 7): S783.
	Background: Recurrent ovarian clear cell carcinoma (OCCC) has an abysmal prognosis with only 6~8% ORR in chemotherapy. Antiangiogenic therapy and immunotherapy might have potential efficacy in OCCC due to the unique clinicopathological characteristics, gene expression profile, and immune microenvironment. Moreover, anti-PD-1 + Bev has shown certain efficacy in renal clear cell carcinoma, which exhibits similar gene expression profiles to OCCC. Herein, we aim to investigate the potential benefit of Sintilimab (PD-1 antibody) + Bev combination therapy for recurrent/persistent OCCC patients. Method(s): This INOVA study followed Simon's 2-stage design. A total of 38 recurrent/persistent OCCC patients with at least one-line pretreated platinum-containing chemotherapy were planned to be recruited. Patients receive Sin (200mg iv. q3w) and Bev (15mg/kg iv. q3w) until disease progression or intolerable toxicity, up to 2 year and 22 cycles, respectively. The primary endpoint was investigator evaluated objective response rate (ORR) per RECIST 1.1. If more than 1 of 17 patients achieved objective response in stage 1, the study will enter stage 2. Result(s): Between April 8, 2021 and April 25, 2022 (data cutoff), 23 patients had been enrolled, with median age of 58 (range,28-67) and 73.9% were Bev naive. All patients received prior platinum-containing chemotherapy. The median lines of treatment were 3 (range, 2-8). 18 of 22 patients (81.8%) were platinum-resistant relapsed. 20 patients were evaluable with at least one radiological evaluation after base line. 8 patients achieved objective response which inferred an ORR of 40.0% (1 CR, 7 PR; 95% CI, 19.1%-63.9%) and a DCR of 75.0% (8 OR, 7 SD; 95% CI, 50.9%-91.3%). Frequently occurring adverse events were grade 1-2, including proteinuria (33.3%), hypothyroidism (27.8%) and ALT, AST elevation (16.7%). Only one (5.6%) patient had a grade 3 immune myocarditis. Conclusion(s): Sintilimab and bevacizumab combination therapy as a chemo-free regimen exhibites promising efficacy and favorable safety for recurrent/persistent OCCC patients. The trial is still recruiting, more data would be further analyzed and reported. Clinical trial identification: NCT04735861. Legal entity responsible for the study: The authors. Funding(s): Beijing CSCO Clinical Oncology Research Foundation. Disclosure: All authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Liu, Y., et al. (2022). "Effectiveness and safety of acupuncture for insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis." MedRxiv.
	Objective. To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate acupuncture's clinical effect of on insulin resistance (IR) in women with polycystic ovary syndrome (PCOS). Methods. PubMed, Cochrane Library, Embase databases, and Chinese databases, including China National Knowledge Infrastructure (CNKI), Technology Journal Database (VIP), and Wanfang Database, were searched without language restrictions from inception to 20 December 2021. Only RCTs in which acupuncture had been examined as the sole or adjunctive PCOS-IR treatment were included. Additionally, only studies in Chinese databases that had been published in core journals of Peking University were included. Our primary endpoint was homeostasis model assessment of insulin resistance (HOMA-IR). The secondary outcomes were fasting blood glucose (FBG), 2-h postprandial blood glucose (2h-PBG), fasting insulin (FINS), body mass index (BMI), and adverse events. A random-effects model enabled reporting of differences between groups as mean differences, thus minimizing the effects of uncertainty associated with inter-study variability on the effects of different interventions. Results. Our analysis included seven eligible RCTs (N=728 participants). Compared with other treatments, acupuncture therapy yielded a greater mean reduction in BMI (-1.21; 95% CI, -2.41 to -0.02; P=0.05). No significant differences existed between acupuncture and other studied treatments for changes in HOMA-IR (-0.33; 95% CI, -0.87 to 0.22; P>0.05), FBG (-0.43; 95% CI, -0.88 to 0.03; P=0.07), 2h-PBG (-0.40; 95% CI, -0.90 to 0.10; P>0.05), and FINS (-0.65; 95% CI, -2.18 to 0.89; P>0.05). Furthermore, compared with medication alone, a combination of acupuncture and medication yielded a mean reduction in HOMA-IR of -0.63 (95% CI, -1.12 to -0.14; P=0.01) and BMI of -1.36 (95% CI, -2.07 to -0.66; P<0.01). Conclusion. Although acupuncture is not more effective than metformin, the former could be an adjuvant strategy for improving PCOS-IR. Further large-scale, long-term RCTs with strict methodological standards are justified.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Liu, Y., et al. (2023). "Effectiveness and safety of acupuncture for insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis." Heliyon 9(3): e13991.
	Objective: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate acupuncture's clinical effect on insulin resistance (IR) in women with polycystic ovary syndrome (PCOS).; Methods: PubMed, Cochrane Library, Embase databases, and Chinese databases, including China National Knowledge Infrastructure, Technology Journal Database, and Wanfang Database, were searched without language restrictions from inception to December 20, 2021. Only RCTs in which acupuncture had been examined as the sole or adjunctive PCOS-IR treatment were included. Our primary endpoint was the homeostasis model assessment of insulin resistance (HOMA-IR). The secondary outcomes were fasting blood glucose (FBG), fasting insulin (FINS), body mass index (BMI), and adverse events.; Results: Our analysis included 17 eligible RCTs (N = 1511 participants). Compared with other treatments, acupuncture therapy yielded a greater mean reduction in HOMA-IR (MD = -0.15; 95% CI, -0.27 to -0.03; P = 0.01) and BMI (MD = -1.47; 95% CI, -2.46 to -0.47; P = 0.004). Besides acupuncture was associated with a lower risk of adverse events than other treatments (RR, 0.15; 95% CI, 0.10 to 0.22; P < 0.01). Additionally, the combination treatment of acupuncture and medicine is more effective in improving HOMA-IR (MD = -0.91; 95% CI, -1.11 to -0.71; P < 0.01), FBG (MD = -0.30; 95% CI, -0.56 to -0.04; P = 0.02), FINS (MD = -2.33; 95% CI, -2.60 to -2.06; P < 0.01) and BMI (MD = -1.63; 95% CI, -1.94 to -1.33; P < 0.01) than medicine alone.; Conclusions: Acupuncture is relatively effective in improving HOMA-IR and BMI in PCOS-IR. Besides, it's safer than other treatments and could be an adjuvant strategy for improving PCOS-IR. Further large-scale, long-term RCTs with strict methodological standards are justified.; Competing Interests: The authors declare no competing interests. (© 2023 The Authors.)

Liu, Y., et al. (2022). "Synergistic Cytotoxicity Effect of 5-Fluorouracil and SHP2 Inhibitor Demethylincisterol A3 on Cervical Cancer Cell." Anti-Cancer Agents in Medicinal Chemistry 22(7): 1313-1319.
	Background: Demethylincisterol A3 (DTA3) has been identified as an SHP2 inhibitor and suppresses the growth of many cancer cells. 5-Fluorouracil (5-FU) is widely used for the clinical treatment of various cancers. However, the combination effects of 5-FU and DTA3 on cervical cancer cells remain unknown.; Objective: This study evaluates the mechanism of the combination effects of 5-FU and DTA3 in cervical cancer cells.; Methods: The synergistic cytotoxic effects of 5-FU and DTA3 in cervical cancer cells were calculated. Apoptosis was analysed by flow cytometry. Western blot analyses were used to examine the related signalling pathways.; Results: DTA3 and 5-FU synergized to induce apoptosis and repress proliferation of cervical cancer cells by downregulating the activation of PI3K/AKT and NF-κB signalling pathways. We provided evidence that the upregulation of SHP2 expression by transfection significantly inhibited the cytotoxicity of 5-FU and DTA3. SHP2 knockdown enhanced the anti-proliferation activity of 5-FU, indicating targeting SHP2 sensitized cervical cancer cells to 5-FU.; Conclusion: Our study demonstrates that SHP2 inhibitor DTA3 and 5-FU have a synergistic cytotoxic effect on cervical cancer cells. The synergistic combination of SHP2 inhibitor and 5-FU may present a promising strategy for the treatment of cervical cancer. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Liu, Y., et al. (2024). "The impact of lymphadenectomy on ovarian clear cell carcinoma: a systematic review and meta-analysis." World Journal of Surgical Oncology 22(1): 37.
	Background: Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients.; Methods: We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460).; Results: Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60-0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34-0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60-1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64-1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation.; Conclusion: Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies. (© 2024. The Author(s).)

Liu, Y., et al. (2021). "Dienogest as a Maintenance Treatment for Endometriosis Following Surgery: A Systematic Review and Meta-Analysis." Frontiers in Medicine 8: 652505.
	This study aimed to comprehensively assess the value of Dienogest (DNG) as a maintenance treatment following conservative surgery for endometriosis in terms of the outcomes of disease and pregnancy. We searched for relevant studies and trials up to November 2020 from PubMed, Cochrane Library, Medline, and EMBASE databases as well as the Web of Science. Patients who received DNG maintenance treatment were compared to those who received other treatments (OT), including the levonorgestrel-releasing intrauterine system (LNG-IUS) and gonadotropin-releasing hormone analogs (GnRH-a), or non-treatment (NT). The primary outcomes were disease recurrence and pregnancy rates. Eleven studies were included in this meta-analysis. The pooled analysis indicated that DNG maintenance treatment was associated with a lower rate of disease recurrence. A significant difference was observed in DNG maintenance treatment compared with NT, but not with OT, in the pregnancy rates postoperatively. Moreover, DNG maintenance treatment was related to a significant increase in vaginal bleeding and weight gain. DNG can be recommended as a maintenance treatment for patients with endometriosis to decrease the rates of disease recurrence following conservative surgery. However, DNG maintenance treatment has no advantage in improving pregnancy rates compared to OT.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Liu, Gong, Gou, Liu and Li.)

Liu, Y., et al. (2021). "The Anti-osteoporosis Effects of Natto on Bone Mineral Density in Perimenopausal Women." Current medicinal chemistry 28(25): 5191-5200.
	Objective and Aims: This study aims to conduct a systematic review and meta-analysis for prospective studies to investigate the improvement effects of natto on bone mineral density (BMD) in perimenopausal women.; Methods: PubMed, EMBASE and Cochrane database searched upto February 2019. This study was carried out according to the PRISMA guidelines10 for systematic reviews. The protocol of the review was registered in the PROSPERO registry (CRD42019133183).; Results: The review identified 3 unique prospective studies comprising 1658 non-overlapping participants. Meta-analysis showed that natto could significantly improve lumbar bone mineral density (BMD) (P=0.002, WMD=0.26; 95% CI:0.09-0.43) in cohort studies. However, the randomized controlled study showed no statistical difference between the two (P=0.31, WMD=0.05; 95% CI:- 0.05-0.15). In addition, natto significantly improved the BMD of the femoral neck in a cohort study and randomized control study (P=0.03, WMD=0.42). 95% CI:0.05-0.79, I2= 72%); (P < 0.0001, WMD=0.16; 95% CI:0.08-0.24), respectively. However, all studies demonstrated that natto has no improvement effects on a hip joint (BMD). In that, the cohort study showed no statistical significance between the natto intake group and the control group (P=0.21, WMD=0.10). 95% CI:-0.06-0.25, I2= 18%) and the randomized controlled study also showed no statistical significance between the natto intake group and the control group (P=0.09, WMD=-0.06). 95% CI:-0.13- 0.01).; Conclusion: Through our current systematic review and meta-analyize of these prosepctive studies of natto's anti-osteoporostic effecs on BMD, we found that the dietary intake of natto demonstrated a improving effects on the BMD of the femoral neck, but has no effects on the hip joint. Such interesting results may be related to the differences between anatomical structure between various tissues. Besides that, the results of the RCT study and cohort study on the lumbar spine were not the same, which may be related to the fact that participants in the RCT study were Caucasian and participants in the cohort study were Asian. Therefore, more large-sample and high-quality RCT studies are needed to further clarify the improvement effect of natto on osteoporosis. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Liu, Y., et al. (2022). "Comparison of adverse events of laparoscopic versus open surgery on cervical cancer." Asian journal of surgery 45(12): 2999-3000.
	
Liu, Y., et al. (2021). "Improvement of Insulin Sensitivity Increases Pregnancy Rate in Infertile PCOS Women: A Systemic Review." Frontiers in Endocrinology 12: 657889.
	Background: Polycystic ovary syndrome (PCOS) is the most common cause of infertility in reproductive-age women. Insulin increases steroidogenesis, deranges granulosa cell differentiation, and affects follicle growth. However, results from randomized control trials (RCTs) were heterogeneous, and little strong evidence associated actual achievement of insulin sensitivity (IS) improvement with reproductive outcomes.; Objectives: To identify evidence of the reproductive benefit of IS improvement in infertile PCOS women by analyzing eligible RCTs.; Search Strategy: Different search strategies with unlimited keywords, including treatment, therapy, intervention, polycystic ovary syndrome/PCOS, insulin resistance, pregnancy, conceive, live birth, and randomized controlled trials/RCT were used in databases including Pubmed, Embase, and Web of Science to November 20th, 2021.; Data Collection and Analysis: Two authors independently abstracted study details and assessed study quality.; Main Results: Ten RCTs that covered different races and met the inclusion criteria were included for analysis and discussion. Clinical pregnancy rate was increased in infertile PCOS women when they had significant improvement of IS after treatment regardless of the various interventions (non-surgical). The benefits of IS improvement appeared superior in PCOS women without severe obesity. The effect of IS improvement on pregnancy rate was independent of the change of BMI.; Conclusions: Nonsurgical therapeutic strategies that promote superior IS improvement may aid infertile PCOS women to increase their possibility of successful pregnancy regardless of the various interventions. The improvement of IS might be more important than the reduction of BMI in the improvement of pregnancy rate in infertile PCOS women.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Liu, Li, Yan, Liu, Ma and Tong.)

Liu, Y., et al. (2022). "Effectiveness of Low-Frequency Electrical Stimulation for Radical Hysterectomy Women: Systematic Review and Meta-Analysis." Gynecologic and Obstetric Investigation 87(5): 266-273.
	Introduction: The aim of the study was to explore the effects of low-frequency electrical stimulation (LFES) in preventing urinary retention after radical hysterectomy (RH) in women with cervical cancer.; Methods: Seven electronic bibliographic databases were searched from inception to December 25, 2021. The mean difference (MD) or risk ratio (RR) with its corresponding 95% CI was selected as effect size. The meta-analysis of all data was conducted using RevMan 5.4 and the evidence was summarized according to GRADE (the grading of recommendation, assessment, development, and evaluation).; Results: Twelve randomized control trials consisting of 1,033 women with cervical cancer who had undergone RH were included. Compared with women in the control group, women receiving LFES had improved therapeutic effect (RR = 0.22, 95% CI: 0.16-0.29) and reduced residual urine volume (MD = -32.27, 95% CI: -34.10 to -30.43) and catheter retention time (MD = -4.46, 95% CI: -5.17 to -3.76) following treatment. Muscle strength scores of pelvic floor type I and type II muscle fibers in the LFES group were also higher than in the control group (MD = 1.07, 95% CI: 0.91-1.24).; Conclusion: LFES may be an effective auxiliary treatment for women with cervical cancer after hysterectomy, which can help reduce the duration of indwelling urethral catheter and residual urine volume. (© 2022 S. Karger AG, Basel.)

Liu, Y., et al. (2022). "Letrozole cotreatment with progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing IVF treatment." Frontiers in Physiology 13: 965210.
	Background: Progestin is an alternative to gonadotropin-releasing hormone (GnRH) analogues in the follicular phase to suppress the premature luteinizing hormone (LH) surge in women with polycystic ovary syndrome (PCOS). However, progestin-primed ovarian stimulation (PPOS) is always accompanied by increased pituitary suppression and gonadotropin consumption. Previous studies suggested that letrozole appeared to have the potential to reduce the total gonadotropin dose required for ovarian stimulation. A retrospective cohort study was performed to evaluate the efficacy of PPOS with or without letrozole in infertile women with PCOS. Methods: This retrospective cohort study included 448 women with PCOS who underwent controlled ovarian stimulation (COS) with human menopausal gonadotropin (hMG) and medroxyprogesterone acetate (MPA) (n = 224) or hMG and MPA cotreatment with LE (n = 224) from January 2018 to March 2021 after propensity-score matching. The primary outcome measure was the hMG dose. The secondary outcomes were the durations of ovarian stimulation, the implantation rate, the number of oocytes retrieved and viable embryos, oocyte maturity and fertilization rates, the percentage of women with profound pituitary suppression (luteinizing hormone [LH] <1.0 IU/L on the trigger day). Results: The hMG doses (1949.89 ± 725.03 IU vs 2017.41 ± 653.32 IU , p > 0.05) and durations of ovarian stimulation (9.03 ± 1.79 days vs 9.21 ± 2.18 days , p > 0.05) were similar between the two groups. The implantation rate was significantly higher in the study group (MPA + hMG + LE) than in the control group (MPA + hMG) (42.22 vs 34.69%, p < 0.05). The numbers of oocytes and embryos retrieved were similar between the two groups. Interestingly, letrozole cotreatment was associated with decreased oocyte maturity and fertilization rates in comparison with standard PPOS protocols even though mature and fertilized oocyte yields were comparable. Compared with those in the control group, the LH values on the trigger day were significantly higher in the study group, together with significantly reduced pituitary suppression. Conclusion: Letrozole combined with PPOS cannot reduce hMG consumption in PCOS patients undergoing IVF treatment and shows no beneficial effect on cycle characteristics of COS. However, letrozole supplementation manifests as a superior implantation rate to that of the standard PPOS protocol in women with PCOS.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Liu, Lin, Chen, Mao, Wang, Chen, Yu and Kuang.)

Liu, Y., et al. (2023). "Letrozole cotreatment improves the follicular output rate in high-body-mass-index women with polycystic ovary syndrome undergoing IVF treatment." Frontiers in Endocrinology 14: 1072170.
	Background: Women who have polycystic ovary syndrome (PCOS) with high body mass index (BMI) typically have an attenuated ovarian response and decreased follicular size, which are linked to unfavourable clinical outcomes following in vitro fertilization (IVF) therapy. The follicular output rate (FORT), a qualitative indicator of follicular response, seems to be positively linked to the clinical outcomes of IVF. Progestin-primed ovarian stimulation (PPOS) has become an alternative to gonadotropin-releasing hormone (GnRH) analogues to inhibit the premature luteinizing hormone (LH) surge. As letrozole (LE) shows promise in enhancing ovarian response, we compared PPOS with and without LE for PCOS in high BMI women with a focus on the FORT and associated clinical and pregnancy outcomes.; Methods: For the recruited 1508 women, ten variables including AFC; age; basal sex hormone level; BMI; infertility type; period of infertility and number of previous IVF attempts were chosen in the propensity score matching (PSM) model to match 1374 women who taken the MPA+ hMG protocol with 134 women who received the MPA+ hMG+ LE treatment at a 1:1 ratio. FORT was selected as the primary outcome measure. The number of oocytes retrieved, viable embryos, hMG dosage, duration, oocyte maturity rate, fertilization rate, and implantation rate were established as secondary outcomes.; Results: FORT was substantially elevated in the MPA+hMG+LE group compared with the MPA+hMG group (61% [35%, 86%] vs. 40% [25%, 60%], P <.001). Interestingly, the LE cotreatment group had a considerably lower mature oocyte rate despite having a similar number of mature oocytes and embryos recovered. The average hMG dosages and durations in the study group were similar to those in the control group. The implantation rate in the study group was numerically higher but without statistic significant than that in the control groups (43.15% (107/248) vs. 38.59% (115/298), OR 1.008, 95% CI 0.901-1.127; P >.05).; Conclusion: The effect of LE combined with PPOS on FORT is better than the effect of the standard PPOS treatment in women with PCOS and a high BMI, but there is no substantially beneficial impact on pregnancy outcomes or the cycle features of COS, including consumption of hMG.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Liu, Lin, Shen, Zhu and Kuang.)

Liu, Y., et al. (2021). "The efficacy and safety of metformin combined with simvastatin in the treatment of polycystic ovary syndrome: A meta-analysis and systematic review." Medicine 100(31): e26622.
	Background: Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent. It is necessary to conduct a meta-analysis to explore the efficacy and safety of metformin combined with simvastatin in the treatment of PCOS, to provide evidence supports for the treatment of PCOS.; Methods: We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to evaluate the synthesized effects.; Results: Nine RCTs with a total of 746 PCOS patients were included. The synthesized results indicated that the combined use of metformin and simvastatin are more beneficial to reduce the total cholesterol (SMD -2.66, 95% CI -3.65 to -1.66), triglycerides (SMD -1.25, 95% CI -2.02 to -0.49), low density lipoprotein (SMD -2.91, 95% CI -3.98 to -1.84), testosterone (SMD -0.64, 95% CI -1.13 to -0.15), fasting insulin (SMD -1.17, 95% CI -2.09 to -0.26) than metformin alone treatment in PCOS patients (all P < .001), and there was no significant difference in the high density lipoprotein (SMD -0.05, 95% CI -0.56-0.46), luteinizing hormone (SMD -0.58, 95% CI -1.66 to -0.50), follicle stimulating hormone (SMD 0.41, 95% CI -0.78-1.59), prolactin (SMD -1.38, 95% CI -2.93-0.17), fasting blood sugar (SMD 0.23, 95% CI -0.52-0.97), and insulin sensitivity index (SMD -0.17, 95% CI -0.48-0.15) between experimental and control groups (all P > .05).; Conclusions: Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar. However, the safety of this therapy still needs to be further explored in clinical studies with high-quality and large samples.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Liu, Y., et al. (2022). "The best postoperative adjuvant therapy for patients with early stage cervical adenosquamous carcinoma." BMC Women's Health 22(1): 112.
	Background: Cervical adenosquamous carcinoma (ASC) was previously thought to be a subtype of cervical adenocarcinoma, but recent studies have found that the clinical features of the two diseases are different. Moreover, the pathological characteristics, survival, prognosis, and optimal ASC therapy remain unknown. This study aims to retrospectively analyze the postoperative survival of patients with early-stage ASC and to evaluate their condition after treatment with postoperative concurrent chemoradiotherapy (CCRT) and prophylactic irradiation of the para-aortic lymphatic drainage area.; Methods: This study enrolled 131 patients with pathologically confirmed ASC screened from 3502 patients with confirmed stage I-II cervical cancer diagnosis who had completed surgical treatments in our hospital. Among the 131 enrolled patients, 75 patients received CCRT, 33 patients received chemotherapy (CT), and 23 patients did not receive adjuvant treatment (named surgery alone (S alone). Of the 75 patients CCRT, 43 patients received prophylactic irradiation of the para-aortic lymphatic drainage area. The efficacy of the postoperative treatments of patients among groups (CCRT, CT, and S alone) was compared.; Results: The median follow-up time, age, and overall survival (OS) were 76 months, 43 years, and 74 months, respectively. The 3- and 5-year survival rates were 82% and 71.4%, respectively. The median disease-free survival (DFS) was 64 months. Cox regression analysis showed that postoperative adjuvant treatment modalities and positive lymph node metastases were associated with OS and DFS. Patients who received CCRT treatment had higher OS and DFS than those with CT and S alone. Prophylactic irradiation of the para-aortic lymphatic drainage area did not improve the OS and DFS of patients with CCRT treatment. However, further subgroup analysis suggested that it might improve survival rates in patients who had positive pelvic lymph nodes as confirmed by postoperative pathology.; Conclusion: Postoperative CCRT improved the survival rates in patients with early-stage ASC. The value of prophylactic irradiation of the para-aortic lymphatic drainage area remains debatable, but it may benefit patients with pelvic lymph node involvement. (© 2022. The Author(s).)

Liu, Y., et al. (2023). "The effect of prophylactic chemotherapy on treatment outcome of postmolar gestational trophoblastic neoplasia." BMC Women's Health 23(1): 1.
	Objective: To evaluate whether prophylactic chemotherapy (P-chem) increased the drug resistance rate of postmolar GTN and whether the first-line chemotherapy should be different from P-chem. Method(s): Postmolar GTN received P-Chem was defined as P-Chem group. Postmolar GTN without P-chem was randomly selected as control group according to the ratio of 1:3 (P-chem:control) and matched by age for low risk and high risk GTN separately. Result(s): Totally 455 low-risk and 32 high-risk postmolar GTN patients were included. WHO risk score, chemotherapy cycles to achieve hCG normalization and resistant rate were similar between P-chem (27 cases) and control (81 cases) group. Among low-risk GTN patients, interval from hydatidiform mole to GTN was significantly longer in P-chem group than control (44 vs 69 days, P = 0.001). Total chemotherapy cycles and resistant rate were similar between low-risk GTN treated with same agent as P-chem (group A) and alternative agent (group B). But group A needed more chemotherapy cycles to achieve hCG normalization than group B. Conclusion(s): P-chem delayed the time to GTN diagnosis, but didn't increase risk score or lead to drug resistance of postmolar GTN. Alternative agent different from P-chem had the potential of enhancing chemotherapy response in low- risk postmolar GTN.Copyright © 2023, The Author(s).

Liu, Y., et al. (2022). "Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study." BMC Women's Health 22(1): 435.
	Background: To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs).; Methods: Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed.; Results: The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P &lt; .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment.; Conclusion: Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment. (© 2022. The Author(s).)

Liu, Y., et al. (2020). "Efficacy of vitamin D supplementation on polycystic ovary syndrome: A meta-analysis." Chinese Journal of Evidence-Based Medicine 20(6): 695-701.
	Objective To systematically review the efficacy of vitamin D supplementation on patients with polycystic ovary syndrome (PCOS). Methods PubMed, EMbase, The Cochrane Library, Web of Science, EBSCO, CBM, WanFang Data, CNKI and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy of vitamin D supplementation for PCOS from inception to July 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 11 RCTs involving 692 patients were included. The results of meta-analysis showed that compared with placebo, vitamin D could reduce the level of hypersensitive C-reactive protein (hs-CRP) (MD=-0.54, 95%CI -1.00 to -0.08, P=0.02) and total testosterone (MD=-0.17, 95%CI -0.29 to -0.05, P=0.004), and increase endometrial thickness (MD=1.78, 95%CI 0.49 to 3.06, P=0.007). However, there were no significant differences between two groups in the incidence of sex hormone binding globulin (SHBG) level and hypertrichosis's score (mF-G) (P>0.05). Conclusions Current evidence indicates that vitamin D supplementation can significantly reduce the level of total testosterone and hs-CRP, and increase endometrial thickness of PCOS. Due to the limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions.Copyright © 2020 West China University of Medical Science. All rights reserved.

Liu, Y.-N., et al. (2020). "[Meta-analysis of Kuntai Capsules combined with GnRH-a in treatment of endometriosis]." Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 45(8): 1933-1941.
	To systemically evaluate the efficacy and safety of Kuntai Capsules combined with GnRH-a in the treatment of endome-triosis. The databases of CNKI, WanFang, VIP, PubMed, EMbase and Cochrane Library were searched from their establishment to May 2019 to collect the randomized controlled trials of Kuntai Capsules combined with GnRH-a in the treatment of endometriosis. The data were searched, screened and extracted by two researchers according to the inclusion and exclusion criteria, and the data were analyzed by using RevMan 5.3 software. A total of 58 articles were collected and 13 studies were included. The total sample size was 1 041 cases, including 523 cases in the experimental group and 518 cases in the control group. The results of Meta-analysis showed that Kuntai Capsules combined with GnRH-a can reduce the level of follicle stimulating hormone(FSH), luteinizing hormone(LH) and estradiol(E&#95;2) in patients with endometriosis as compared with GnRH-a alone. With a low incidence of adverse events of peri-meno-pausal symptoms during treatment(RR=0.46, 95%CI[0.35, 0.60], P<0.000 01), it can reduce the VAS score of dysmenorrhea(MD=-1.85,95%CI[-1.92,-1.78],P<0.000 01). The recurrence rate in the combined treatment group was lower than that in the control group(RR=0.27, 95%CI[0.09,0.77], P=0.01). This study showed that Kuntai Capsules combined with GnRH-a can reduce the level of FSH, LH and E&#95;2 in patients with endometriosis, reduce the VAS score of dysmenorrhea, with lower incidence of adverse events and recurrence rate, but it still needs large-scale, multicenter, randomized, double-blind and high-quality clinical trials for support and evidence.

Liu, Z., et al. (2022). "Application Effect of Laparoscopic Myomectomy and Comprehensive Rehabilitation Nursing on Patients with Uterine Fibroids." Computational and mathematical methods in medicine 2022: 4018803.
	Background: Uterine fibroids are most common in women aged 30-50 and are the most common benign gynecological tumors. Relevant data suggest that about 25% of patients with uterine fibroids are at childbearing age. Uterine fibroids not only cause the discomfort symptoms, and affect the pregnancy, but also have certain malignant transformation risk, thus needed to be treated positively and promptly.; Aim: This study is aimed at exploring the effect of laparoscopic myomectomy and comprehensive rehabilitation nursing on patients with uterine fibroids.; Methods: The clinical data of 110 cases of uterine fibroids admitted to our hospital from August 2019 to December 2021 were analyzed retrospectively, and they were divided into two groups according to postoperative rehabilitation strategies. Both groups were treated with laparoscopic myomectomy. The A group was treated with routine rehabilitation strategy, while the B group was treated with comprehensive rehabilitation nursing strategy. The differences in operation-related indicators, stress factors, inflammatory factors, nutritional indicators, knowledge mastery, occurrence of adverse symptoms and pain scores, negative emotion scores, nursing satisfaction, and simplified comfort status scale (GCQ) scores between the two groups under nursing strategies were compared.; Results: The postoperative exhaust time (13.14 ± 2.03) h, bed time (9.86 ± 1.94) h, postoperative hospital stay (4.37 ± 1.31) d, and total hospital stay (6.78 ± 1.69) d in the B group were shorter than those in the A group, and the hospitalization expenses (0.74 ± 0.25) million were less than those in the A group ( P < 0.05). Before operation, stress factors, inflammatory factors, and nutritional indexes were compared between the two groups ( P > 0.05). On the 3rd day after operation, tumor necrosis factor- α (TNF- α ), cortisol (Cor), norepinephrine (NE), and interleukin-1 β (IL-1 β ) in the two groups showed a significantly upward trend compared with those before operation, and albumin and transferrin were significantly fell compared with those before operation. However, the values of stress factor and inflammatory factor in the B group were significantly lower than those in the A group, and the values after the decrease of nutritional index were significantly higher than those in the A group ( P < 0.05). The pain scores at 24 h, 48 h, and 72 h after operation in the B group were significantly lower than those in the A group ( P < 0.05). Negative emotions, nursing satisfaction, and GCQ scores were compared between the two groups before intervention ( P > 0.05). After the intervention, the scores of Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) in the two groups were significantly lower than those before the intervention, and the scores of nursing satisfaction and GCQ were higher than those before the intervention. The values of negative emotions in the B group after the decline were significantly lower than those in the A group, while the values of nursing satisfaction and GCQ after the increase were higher than those in the A group ( P < 0.05). The excellent and good rate of knowledge acquisition in the B group was 94.55% (52/55), which was significantly higher than 78.18% (43/55) in the A group ( P < 0.05). The incidence of adverse symptoms in the B group was 9.09% (5/55), which was lower than 21.82% (12/55) in the A group, while the difference was not statistically significant ( P > 0.05).; Conclusion: Laparoscopic myomectomy combined with comprehensive rehabilitation nursing can reduce the postoperative stress state of patients with uterine fibroids, improve patient satisfaction, reduce adverse emotions, and promote rehabilitation.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Zhihong Liu et al.)

Liu, Z., et al. (2023). "Letrozole Compared With Clomiphene Citrate for Polycystic Ovarian Syndrome: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 141(3): 523-534.
	Objective: To estimate the effect of letrozole and clomiphene citrate in women with infertility and polycystic ovarian syndrome (PCOS).; Methods of Study Selection: MEDLINE through PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched for relevant studies from inception to February 1, 2022. Two reviewers retrieved, filtered, and extracted data independently using the bibliographic software EndNote X9 and Excel workbook. We included randomized controlled trials (RCTs) reporting ovulation induction outcomes in women with infertility and PCOS treated with either letrozole or clomiphene citrate followed by timed intercourse or intrauterine insemination. The data were merged into a mean difference or risk ratio (RR) with 95% CI, depending on variable types.; Tabulation, Integration, and Results: Data collection and organization were conducted in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Twenty-nine RCTs were eligible, which included 3,952 women and 7,633 ovulation induction cycles. We acquired evidence from 22 RCTs for the ovulation rate, 28 RCTs for the clinical pregnancy rate, and eight RCTs for live-birth rate. Pooled analysis indicated that letrozole treatment prevailed against clomiphene citrate in ovulation rate (RR 1.14, 95% CI 1.06-1.21, P <.001), clinical pregnancy rate (RR 1.48, 95% CI 1.34-1.63, P <.001), and live-birth rate (RR 1.49, 95% CI 1.27-1.74, P <.001).; Conclusions: Letrozole was associated with improved ovulation, pregnancy, and live-birth rates compared with clomiphene citrate. We recommend letrozole over clomiphene citrate as an ovulation induction drug in women with infertility and PCOS, although the quality of the evidence is mixed.; Systematic Review Registration: PROSPERO, CRD42022308777.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Liu, Z., et al. (2022). "Overexpression of hypoxia-inducible factor 1α and excessive vascularization in the peri-implantation endometrium of infertile women with chronic endometritis." Frontiers in Endocrinology 13: 1001437.
	Objective: Chronic endometritis (CE) contributes to impaired endometrial receptivity and is closely associated with poor in vitro fertilization (IVF) outcomes. However, the mechanisms underlying CE are unclear. Here, we investigated the role of the hypoxic microenvironment and endometrial vascularization in the peri-implantation endometrium of infertile women with CE.; Methods: This retrospective study involved 15 fertile women and 77 infertile patients diagnosed with CE based on CD138+ ≥1/10 high-power fields (HPFs). The CE patients were divided into Group 1 (CD138+ 1-4/10 HPFs, 53 cases) and Group 2 (CD138+ ≥5/10 HPFs, 24 cases). The expression levels of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in peri-implantation endometrium were assessed by qRT-PCR and western blot analyses. Spatial levels of HIF1α, VEGFA, and VEGFR2 in various endometrial compartments was determined using immunohistochemistry and H -score analysis. Microvascular density (MVD) was determined using CD34 staining and scored using Image J. Finally, we used qRT-PCR to assess changes in the expression of HIF1α, VEGFA, and VEGFR2 in CE patients after treatment with first-line antibiotics.; Results: Relative to Group 1 and control group, during the implantation window, protein and mRNA levels of HIF1α, VEGFA, and VEGFR2 were markedly high in Group 2 ( P <0.05). H -score analysis showed that HIF1α, VEGFA, and VEGFR2 in the luminal, glandular epithelium, and stromal compartments were markedly elevated in Group 2, comparing to control group and Group 1 ( P <0.05). Moreover, markedly elevated MVD levels were observed in Group 2. Notably, the above indexes did not differ significantly in the control group versus Group 1. Treatment with antibiotics significantly suppressed the endometrial HIF1α and VEGFA levels in CE-cured patients.; Conclusions: Here, we for the first time report the upregulation of HIF1α, VEGFA, and VEGFR2, as well as excessive endometrial vascularization in the peri-implantation endometrium of CE patients. Our findings offer new insights into reduced endometrial receptivity in CE-associated infertility.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Liu, Liu, Li, Sun, Yu, Zhang, Zhu, Ma, Wang, Lai and Bao.)

Liu, Z., et al. (2022). "The Clinical Efficacy of Personalized Embryo Transfer Guided by the Endometrial Receptivity Array/Analysis on IVF/ICSI Outcomes: A Systematic Review and Meta-Analysis." Frontiers in Physiology 13: 841437.
	Objective: To assess the prevalence of displaced window of implantation (WOI) in infertile women, and the clinical utility of personalized embryo transfer (pET) guided by the endometrial receptivity array/analysis (ERA) on IVF/ICSI outcomes. Methods: The protocol was registered at Prospero: CRD42020204237. We systematically searched all published English literature related to the prevalence of WOI displacement and ongoing pregnancy rate/live birth rate in the overall good-prognosis infertile patients (GPP) and/or repeated implantation failure (RIF) patients undergoing IVF/ICSI-ET cycles after ERA test until August 2021. Result(s): 11 published studies were enrolled in the final analysis. The estimate of the incidence of WOI displacement based on ERA was 38% (95%CI 19-57%) in GPP and 34% (95%CI 24-43%) in RIF, respectively. There was no difference in OPR/LBR between patients undergoing routine ET without ERA test and those who following pET with ERA (39.5 vs. 53.7%, OR 1.28, p = 0.49, 95%CI 0.92-1.77, I 2 = 0%) in relative GPP. Notably, the meta-analysis revealed that OPR/LBR of patients with RIF undergoing pET who had non-receptive ERA increased to the level of to those undergoing sET with receptive ERA (40.7 vs.49.6%, OR 0.94, p = 0.85, 95%CI 0.70-1.26, I 2 = 0%). Conclusion: Considering the approximately one third of infertile women could suffered from displaced WOI, the ERA test emerged as a promising tool. Although the present meta-analysis demonstrates that patients with general good-prognosis may not benefit from ERA, pET guided by ERA significantly increases the chances of pregnancy for non-receptive patients with RIF of endometrial origin.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Liu, Liu, Wang, Zhao, He, Lai, Qu, Wang, Zhao and Bao.)

Liu, Z., et al. (2022). "Clinical and pelvic floor ultrasound characteristics of pelvic organ prolapse recurrence after transvaginal mesh pelvic reconstruction." BMC Women's Health 22(1): 102.
	Background: Recurrence of pelvic organ prolapse (POP) after transvaginal mesh (TVM) implantation pelvic floor reconstruction surgery remains an unresolved problem in clinical practice. In this retrospective observational study, clinical and pelvic floor ultrasound (PFUS) parameters were analyzed in order to identify high-risk factors of POP recurrence.; Methods: The clinical and PFUS data from September 2013 to November 2019 of patients who underwent TVM were retrospectively analyzed. The patients with prolapse recurrence on postoperative follow-up diagnosed by PFUS were selected as case group, the clinical and PFUS parameters of them were compared with the control group in which the patients had no sign of prolapse recurrence. Univariate and multivariate regression analyses were performed based on age, BMI, gravidity, parity, surgical history (non-POP hysterectomy and incontinence-or-POP surgery), preoperative POP stage, follow-up in years, levator avulsion and hiatal area (HA) on Valsalva.; Results: Altogether 102 patients entered the study and the median interval between PFUS and TVM surgery was 2.5 years. Univariate analysis showed that levator avulsion and HA were significantly different between case group and control; multivariate regression analysis showed that only HA was related to prolapse recurrence after TVM (OR = 1.202, 95% CI 1.100-1.313, P < 0.001). The area under the ROC curve was 0.775 (95% CI 0.684-0.867, P < 0.001).; Conclusions: Hiatal area on Valsalva was related to prolapse recurrence after TVM surgery and it is an important parameter for postoperative follow-up of TVM surgery. (© 2022. The Author(s).)

Liu, Z., et al. (2020). "The comparison of the effectiveness and safety of drospirone ethinyl estradiol and ethinyl estradiol cyproterone in the treatment of polycystic ovarian syndrome: A protocol for systematic review and meta-analysis." Medicine 99(51): e23811.
	Background: Polycystic ovarian syndrome (PCOS) is an endocrine disorder syndrome with reproductive dysfunction and abnormal glucose metabolism. Persistent non-ovulation, excessive androgens and insulin resistance are important features and they are the most common causes of menstrual disorders in women during childbearing years. At present, the cause of PCOS is not clinically clear. Current studies suggest that it may be due to the interaction of certain genetic genes with environmental factors. It is an important cause of infertility or early miscarriage with the characteristics of various causes and complex clinical manifestations. At present, for the treatment of PCOS patients, clinical treatment mainly includes hypoglycemia, insulin and menstrual regulation and other symptomatic and supportive treatment. Drospirone ethinyl estradiol and ethinyl estradiol cyproterone are 2 of the most commonly used drugs in clinical treatment of PCOS, but there is lack of the evidence of evidence-based medicine. Therefore, this study systematically evaluates the therapeutic effect and safety of PCOS patients with 2 short-acting oral contraceptives, drospirone ethinyl estradiol and ethinyl estradiol cyproterone, which provides the guidance for clinically selecting the appropriate drug to treat PCOS.; Methods: Searching CNKI, WanFang Data, VIP, SinoMed, PubMed, EMbase, Web of Science, and The Cochrane Library database by computer, collecting the randomized controlled studies of DEE and EEC in the treatment of PCOS. The retrieval time limit is from the establishment of each database to July 1, 2020. In addition, tracing the references incorporated into the literature to supplement to the relevant literature. Using the retrieval method by combining the free words and the subject words, and the individual search of different databases is carried out. Meta-analysis is performed using RevMan 5.3 software after 2 researchers independently screens the literature, extracts the data, and evaluates the bias risk included in the study.; Results: This study will systematically evaluate the DEE and EEC in the treatment of PCOS by collecting the required evidence to understand the effects of the 2 drugs on hypersotrophicemia, insulin resistance, lipid metabolism, and the safety during drug use in patients of this class, and the results will be published in highly influential academic journals.; Conclusion: The results of this study will provide theoretical basis for the drug treatment of polycystic ovarian syndrome and provide help in the decision-making of clinical treatment of the disease.; Ethics and Dissemination: In this study, meta-analysis was used to conduct a second study on the published literature. Therefore, this type of systematic review research does not need to be approved by ethics.; Osf Registration Doi: 10.17605/OSF.IO/8GW9M.; Competing Interests: The authors have no conflicts of interests to disclose. (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Liu, Z., et al. (2022). "616TiP Intra-tumor injection of H101 combined with or without radiotherapy in refractory/recurrent/metastatic gynecological malignancies: A prospective, open-label, multi-center, single-arm study." Annals of Oncology 33(Supplement 7): S826.
	Background: Patients with recurrent and radiation/chemotherapy-resistant gynecological cancer carry a poor prognosis. H101 is a recombinant human type-5 adenovirus (Ad5), in which the E1B and E3 gene have been deleted. Previous studies have shown that H101 has anticancer activity and safety in some solid tumors, but the current evidence regarding the effect of H101 on gynecological oncology remains rare. Therefore, the purpose of this clinical trial is to evaluate the effect and safety of H101 intra-tumor injection combined with or without radiotherapy in refractory/recurrent/metastatic gynecological malignancies, and to further explore the mechanism of H101. Trial design: In this prospective, open-label, multi-center, single-arm study, it is estimated 60 patients diagnosed with refractory/recurrent/metastatic cervical cancer, endometrial cancer, uterine sarcoma, ovarian cancer, vaginal cancer or vulvar cancer receiving standard tumor treatment will be enrolled (start date September 26, 2021). Based on individual conditions, H101 are intratumorally injected within 5 consecutive days combined with or without radiotherapy in sequential, three weeks for a cycle (1-4 cycles totally). Simultaneously, the tumor sample, peripheral blood, and urine specimen are collected on day 1 and day 5. The injection dose of H101 is determined by the tumor volume or maximum tumor diameter: 5.0x1011 virus particles (vp) for tumor diameter<=5cm; 1x1012 vp for tumor diameter between 5cm and 10cm, and 1.5x1012vp for tumor diameter>10cm. The primary endpoint is local control (LC). LC will be measured from the start date of injection until the date of progressive disease. The secondary endpoints include objective response rate (ORR), progression-free survival (PFS) and adverse events (AEs). The AEs are monitored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). Study data will be collected and managed using the electronic data capture system (EDC). Patient enrollment is now ongoing and the estimated study duration are 2 years. Clinical trial identification: The study is registered at Clinicaltrials.gov (NCT 05051696). Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Liu, Z., et al. (2022). "A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients." Hereditas 159(1): 40.
	Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development.; Methods: CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan-Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset.; Results: We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups.; Conclusion: In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC. (© 2022. The Author(s).)

Lo, G., et al. (2024). "Ultrasound-guided Lipiodol hysterosalpingography: A prospective study on pregnancy and complication rates." Australian and New Zealand Journal of Obstetrics and Gynaecology.
	Background: Fluoroscopic hysterosalpingography (HSG) with Lipiodol is safe and has a therapeutic effect on fertility: transient in endometriosis-related infertility and sustained in unexplained infertility. Ultrasound is replacing fluoroscopy as the preferred imaging modality for HSG due to comfort and radiation safety (no ionising radiation). The safety of ultrasound-guided Lipiodol HSG is uncertain. Aim(s): Prospectively observe pregnancy and complication rates after ultrasound-guided Lipiodol HSG. Material(s) and Method(s): A single-centre prospective study of women with unexplained infertility undergoing ultrasound-guided Lipiodol uterine bathing and tubal flushing after tubal patency confirmed with ExEm Foam HyFoSy (hysterosalpingo-foam-sonography). Pregnancy outcomes at six months and serum and urinary thyroid function at one, three and eight weeks were recorded. Pain scores were recorded during and immediately after HSG. Descriptive statistics are reported. Result(s): Fifty-two participants were enrolled between July 2019 and April 2021, median age 33 years (range 21-45). Only 45 (87%, 45/52) completed the Lipiodol HSG; 5/7 experienced intravasation during initial HyFoSy. Of 30 women at follow-up, 57% had biochemical (17/30, 95% CI 37%-75%), 53% clinical (16/30 95% CI 34%-72%) and 35% ongoing pregnancies (11/30, 95% CI 20%-56%). The rate of subclinical hypothyroidism (SCH) at two months was 41% (7/17). One intravasation event occurred during Lipiodol HSG (2%, 1/45). Median pain score was 5/10 (range 0-9, interquartile range 2.5-7). No anaphylaxis, infection or oil embolism was observed. Conclusion(s): Outpatient ultrasound-guided Lipiodol HSG was safe, with pregnancy rates comparable to previous studies of fluoroscopic guidance. Rates of intravasation and SCH were also similar, confirming the need to monitor thyroid function.Copyright © 2024 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Lo, S. S., et al. (2019). "The Role of Estrogen Status in the Causation of Female Lower Urinary Tract and Pelvic Floor Dysfunction." Current Bladder Dysfunction Reports 14(3): 139-143.
	Purpose of Review: In this review, we aim to examine current literature focused on the effects of estrogen in causing conditions such as urinary incontinence, overactive bladder, recurrent urinary tract infections, pelvic organ prolapse, and anorectal dysfunction. Recent Findings: Small studies have confirmed the role of local estrogen therapy in the treatment of overactive bladder and recurrent urinary tract infection. Summary: Although well recognized that the female lower urinary tract and pelvic floor are estrogen responsive, there is paucity in the role of estrogen status in causing such conditions.Copyright © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Loaiza-Betancur Andrés, F., et al. (2021). "The effect of exercise training on blood pressure in menopause and postmenopausal women: A systematic review of randomized controlled trials." Maturitas 149: 40-55.
	The prevalence of hypertension is higher in postmenopausal than in premenopausal women. Regular exercise training has been shown to be effective in addressing hypertension. The aim of this systematic review was to synthesize the effect of exercise training on systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in menopausal and postmenopausal women. This review was reported according to the PRISMA statement and registered in PROSPERO. The literature search was done in MEDLINE, Embase, Cochrane CENTRAL and ClinicalTrials. Randomized controlled trials involving menopausal and postmenopausal women undergoing exercise training were included. Two blinded reviewers assessed risk of bias in the included studies by using the Cochrane Risk of Bias tool. A random-effects model was used for all analyses. Significance was set at P < 0.05. Compared with the control group, exercise training resulted in clinically significant reductions on SBP (MD -3.43 mmHg; 95% CI, -5.16, -1.71; P < 0.0001), DBP (MD, -2.25 mmHg; 95% CI, -3.40, -1.11; P = 0.0001) and MAP (MD, -3.48 mmHg; 95% CI, -5.84, -1.11; P = 0.004). Aerobic training (AT) did not produce a significant reduction in SBP, DBP and MAP (P >0.05). Combined training (CT) generated larger reductions. Exercise training generated small but clinically relevant reductions in SBP, DBP and MAP in menopausal and postmenopausal women, younger or older than 65 years, with prehypertension or hypertension. AT did not lead to a clinically relevant improvement in blood pressure (BP) in this population. In addition, CT showed the largest reductions in SBP, DBP and MAP. (Copyright © 2021. Published by Elsevier B.V.)

Locke, G. E., et al. (2022). "Opioid consumption and pain in patients with gynecological cancer who underwent spinal anesthesia vs. general anesthesia for interstitial brachytherapy." Brachytherapy 21(6): 806-813.
	AIMS: Interstitial brachytherapy (ISBT) is an effective option for delivering conformal high dose radiation to the target volume with better organ-at risk sparing but is thought to be more invasive and painful than other methods. This study investigated pain levels and opioid consumption in patients who received spinal anesthesia (SA) or general anesthesia (GA) for their ISBT. MATERIALS AND METHODS: Patients that underwent ISBT from April 2014 to September 2018 were analyzed from a prospective institutional database. The most prevalent malignancies were cervical (45%), recurrent endometrial (27%) and vaginal (20%) cancers. Baseline patient characteristics, radiation treatment details, anesthesia records, and inpatient charts were obtained. Opioid consumption was quantified as oral morphine equivalent per day (OMEq/day) from implantation until removal. Pain score levels were collected by using an 11-point scoring system. RESULT(S): Ninety nine patients received GA and 40 patients received SA as their anesthesia for ISBT. During their first admission, 76 patients (55%) required intravenous opioids. Patients receiving SA had significantly lower mean pain scores on the morning of their procedure 6 (Interquartile range [IQR] 2-8) vs. 0 (IQR: 0-1); p < 0.001]. Pain did not significantly differ between cohorts at any other time. During the first admission, SA patients had a lower median opioid usage of 23 (IQR: 9-47) mg/day compared to GA patients at 38 (IQR: 21-71) mg/day (p = 0.011). No difference in opioid consumption was seen during subsequent admissions. CONCLUSION(S): In patients undergoing ISBT, SA provides better immediate pain control post insertion compared to GA. Patients who received SA used lower amounts of opioids during their first ISBT insertion.Copyright © 2022 American Brachytherapy Society

Loddo, A., et al. (2022). "Hysteroscopic myomectomy: The guidelines of the International Society for Gynecologic Endoscopy (ISGE)." European Journal of Obstetrics and Gynecology and Reproductive Biology 268: 121-128.
	Objective: With this publication, the International Society for Gynecologic Endoscopy (ISGE) aims to provide the clinicians with the recommendations arising from the best evidence currently available on hysteroscopic myomectomy (HM). Study design: The ISGE Task Force for HM defined key clinical questions, which led the search of Medline/PubMed and the Cochrane Database. We selected and analyzed relevant English-language articles, published from January 2005 to June 2021, including original works, reviews and the guidelines previously published by the European Society for Gynecological Endoscopy (ESGE) and the American Association of Gynecologic Laparoscopists (AAGL), in which bibliographies were also checked in order to identify additional references, using the medical subject heading (MeSH) term "Uterine Myomectomy" (MeSH Unique ID: D063186) in combination with ''Myoma" (MeSH Unique ID: D009214) and ''Hysteroscopy" (MeSH Unique ID: D015907). We developed the recommendations through multiple cycles of literature analysis and expert discussion. Result(s): The ISGE Task Force did develop 10 grade 1A-C and 4 grade 2A-C recommendations. For planning HM, evaluation of the uterus with saline infusion sonohysterography (SIS) or combined assessment by transvaginal ultrasound (TVUS) and diagnostic hysteroscopy is recommended (Grade 1A). The use of STEPW (Size, Topography, Extension of the base, Penetration and lateral Wall position) classification system of submucosal leiomyoma (LM) is recommended to predict the complex surgeries, incomplete removal of the LM, long operative time, fluid overload and other major complications (grade 1B). For type 0 LMs, in addition to resectoscopy (slicing technique), morcellation is recommended, being faster and having a shorter learning curve with respect to resectoscopy (grade 1C). For type 1-2 LMs, slicing technique is currently recommended (grade 1C). A fluid deficit of 1000 mL also in case of bipolar myomectomy with saline solution, in healthy women of reproductive age, contains low risk for major complications. Lower thresholds (750 mL) for fluid deficit should be considered in the elderly and in women with cardiovascular, renal or other co-morbidities (Grade 1B). Conclusion(s): HM is the most effective conservative minimally invasive gynecologic intervention for submucous LM. The set of 14 ISGE recommendations can significantly contribute to the success of HM and the safety of patients for whom the choice of appropriate surgical technique, as well as the surgeon's awareness and measures to prevent complications are of the utmost importance.Copyright © 2021 Elsevier B.V.

Lof, P., et al. (2022). "Clinical implementation of routine diagnostic laparoscopy to guide initial treatment in patients with advanced-stage epithelial ovarian cancer in Dutch clinical practice: Evaluation of support and a budget impact analysis." Gynecologic Oncology 165(3): 459-465.
	Objective: In patients with advanced-stage epithelial ovarian cancer (EOC), a diagnostic laparoscopy (DLS) to determine treatment regime prevents futile laparotomies and seems cost-neutral. The uptake of DLS in current practice is unknown. We evaluated the clinical application of routine DLS in treatment planning in patients with advanced-stage EOC in the Netherlands.; Methods: The implementation was evaluated over the period 2017-2019, using a health technology assessment including clinical, organizational, and economic factors. Barriers for implementation were identified and DLS use was assessed using semi-structured surveys with healthcare professionals. Data from the Dutch Gynecological Oncology Audit were used to determine (un)successful CRS rates. To assess the economic impact, we performed a budget impact analysis (BIA) of the combined interventions of DLS and primary CRS.; Results: The DLS use to guide treatment planning increased from 16% to 20%. The majority of the centers did not support routine DLS implementation, mainly because of logistic barriers and its invasive nature. The primary CRS rate of all CRS decreased from 44% to 36%, in favor of interval CRS. The unsuccessful primary CRS rate decreased from 15% to 9% resulting in fewer patients needed a second interval CRS. Consequently, total health care costs decreased from €4.457.496 to €4.274.751.; Conclusions: The implementation of routine DLS for guiding treatment planning in patients with advanced-stage EOC has limited support in the Netherlands. Over the years, total health care costs decreased. For current practice, it is advised that a DLS is useful in case it is uncertain whether a successful primary CRS is feasible based on conventional work-up.; Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Loflin, B. J., et al. (2019). "Vulvodynia: A Review of the Literature." Journal of Pharmacy Technology 35(1): 11-24.
	Objective: To evaluate the literature and educate the pharmacy community about the different treatment options for vulvodynia. Data Sources: Searches were performed through MEDLINE (1946-May 2018) using OVID and EBSCOhost, and Excerpta Medica (1974-May 2018) using EMBASE. Search terms included vulvar vestibulitis syndrome, vestibulodynia, vulvodynia, vulvar pain, provoked vulvar vestibulitis, and vulvodynia treatment. References of all relevant articles were then used to find additional applicable articles. Study Selection and Data Extraction: This review includes articles in the English language and human trial literature. Twenty-five trials explored the use of oral and topical medications in the treatment of vulvodynia. Data Synthesis: Vulvodynia is a poorly understood disease with an unknown etiology. Oral tricyclic antidepressants and gabapentin continue to be the most commonly used treatments for vulvodynia pain. This is due to their ease of use and patient preference. Topical treatments that have efficacy data are amitriptyline, gabapentin, lidocaine, baclofen, and hormones. This route of administration avoids systemic adverse effects and interpatient variability that accompanies oral administration. Alternative therapies more commonly used include physiotherapy, psychotherapy, and surgery. Treatment length may vary due to dose titrations and potential changes in medication therapy. Conclusion(s): Several medication and alternative therapies may be effective in treating vulvodynia. Current studies used wide dosing ranges, making it difficult to standardize therapy. No consistent method of assessing pain was used between studies, as well as a limited number being randomized and placebo controlled. Additional research is needed to increase knowledge and further develop vulvodynia treatments.Copyright © The Author(s) 2018.

Loghmani, L., et al. (2019). "Tubal ligation and endometrial Cancer risk: A global systematic review and meta-analysis." BMC Cancer 19(1): 942.
	Background: Studies on relationship between tubal ligation and endometrial cancer have led to contradictory findings. In several studies, however, a reduced endometrial cancer risk was suggested following tubal ligation. Therefore, a systematic review and meta-analysis was conducted to examine the relationship between tubal ligation and endometrial cancer risk. Method(s): In this systematic review and meta-analysis, PubMed/Medline, Web of Science, Scopus, Embase, and Google Scholar were searched for relevant studies published up to May 30th, 2018. We compared endometrial cancer risk in women with and without tubal ligation in retrieved studies. Result(s): Two hundred nine studies were initially retrieved from the data bases. After exclusion of duplicates and studies which did not meet inclusion criteria, ten cohort and case-control studies, including 6,773,066 cases, were entered into the quantitative meta-analysis. There was 0.90% agreement between two researchers who searched and retrieved the studies. The summary OR (SOR) was reported using a random effect model. Begg's test suggested that there was no publication bias, but a considerable heterogeneity was observed (I2 = 95.4%, P = 0.001). We pooled the raw number of tables cells (i.e. a, b, c, and d) of eight studies. The SOR suggested that tubal ligation was significantly associated with a lower risk of endometrial cancer (SOR = 0.577, 95% CI = 0.420-0.792). Also, given the rare nature of endometrial cancer (< 5%), different effect sizes were considered as comparable measures of risk. Therefore we pooled ten studies and SOR of these studies revealed that tubal ligation was significantly associated with a lower risk of endometrial cancer (SOR = 0.696, 95% CI = 0.425-0.966). Besides that, we pooled eight studies in which adjusted effect sizes were reported and a subsequent analysis revealed that the summary estimate of adjusted odds ratio (SAOR) was significant (SAOR = 0.862, 95% CI = 0.698-1.026). Conclusion(s): This study revealed a protective effect of tubal ligation on endometrial cancer risk (approximately 42% lower risk of cancer). It is recommended that studies should be designed to reveal mechanisms of this relationship.Copyright © 2019 The Author(s).

Lomena-Villalobos, J. A., et al. (2022). "Electroacupuncture versus pelvic floor muscle training for urinary incontinence in women. A retrospective analysis." Revista Internacional de Acupuntura 16(2): 100188.
	Introduction and objectives: Urinary incontinence is highly prevalent. The problem is not always solved with medication and/or surgery and they are not without side effects, which has led to the use of acupuncture for the condition. We compare electroacupuncture with pelvic floor muscle training in women with urinary incontinence. Method(s): This is a retrospective, randomised study of 71 women with urinary incontinence and 2 groups: 37 women received electroacupuncture at R 7 points plus pelvic floor muscle training, and another group of 34 women received only pelvic floor muscle training. Electroacupuncture was performed in one session per week for 12 weeks. All participants performed the exercises at home after prior training. Follow-up was conducted over 1 year. Efficacy was assessed using the Spanish versions of the International Consultation on Incontinence Questionnaire-Short Form and the Bladder Control Self-Assessment Questionnaire. The questionnaires were conducted at baseline and at 3, 6, and 12 months. The safety of electroacupuncture was also assessed. Result(s): The reduced score in both questionnaires was clinically and statistically more significant in the electroacupuncture group. Discussion(s): Electroacupuncture at the R 7 point was identified as more effective than pelvic floor muscle training in women with urinary incontinence, and with very few side effects.Copyright © 2022

Londero Ambrogio, P., et al. (2021). "Hormone Replacement Therapy in Endometrial Cancer Survivors: A Meta-Analysis." Journal of Clinical Medicine 10(14).
	The purpose of this study is to investigate the effect of hormone therapy (HT) on the oncological outcomes of endometrial cancer (EC) survivors. A systematic literature review was conducted in July 2021 to identify studies detailing the effect size for the relationship between HT use in EC and oncological outcomes (survival and disease recurrence). This included studies that evaluated the different recurrence rates among women treated for EC who subsequently underwent HT and those who did not. The collected studies were evaluated for quality, heterogeneity, and publication bias, and a pooled odds ratio (OR) or hazard ratio (HR) was calculated with a confidence interval of 95% (95% CI). In total, 5291 studies were collated, and after the review process, one randomized trial and seven observational studies were included, comprising 1801 EC survivors treated with HT and 6015 controls. The time-dependent analysis could be conducted for four studies, and considering the disease-free survival, the pooled HR of 0.90 (95% CI 0.28 to 2.87) showed no significant differences. However, among Black American women treated with continuous estrogen HT, the HR was 7.58 (95% CI 1.96 to 29.31), showing a significantly increased risk of recurrence for women in this ethnic group. Considering the pooled OR of all included studies 0.63 (95% CI 0.48 to 0.83), a significantly reduced risk of recurrence was found among EC survivors treated with HT. Considering the type of HT, the most risk-reducing was combined estrogen and progestin therapy and the cyclic regimen. Although supporting evidence is based mainly upon observational studies, evidence of no increased risk or even decreased risk was generally found, apart from in Black American women where a significantly increased recurrence risk was evident. The data are rather reassuring for the short-term administration of HT to symptomatic EC survivors. Future studies with a longer follow-up are necessary to better clarify the long-term effects of HT.

London Imperial, C. and L. Hospitals University College (2021). Intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy as a Method of Fertility Preservation.
	No Results Available Procedure: Ultrasound guided laparoscopic ovarian cystectomy|Other: Laparoscopic Ovarian Cystectomy Anti-Mullerian Hormone (AMH) (pmol/L)|Antral Follicle Count (AFC) (n)|Length of hospital stay (days)|Presence of intra-operative cyst rupture (Yes/No)|Duration of surgery (minutes) Female Not Applicable 32 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment IRAS 290747 October 1, 2025

London King's, C., et al. (2021). Community Singing Interventions for Postnatal Depression: a Hybrid Type II Effectiveness-implementation Trial.
	No Results Available Behavioral: Melodies for Mums|Behavioral: Control Community Sessions To assess the effectiveness of group singing interventions on symptoms of postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS)|To assess the acceptability of the intervention using the Acceptability of Intervention Measure (AIM)|To assess whether singing improves (changes) further aspects of mental health, including depression using the Hamilton Depression Rating Scale (HDRS).|To assess whether singing improves (changes) further aspects of mental health, including depression using the Beck Depression Inventory (BDI).|To assess whether singing improves (changes) further aspects of mental health, including stress using the Perceived Stress Scale (PSS)|To assess whether singing improves (changes) further aspects of mental health, including wellbeing using the Office for National Statistics Wellbeing Scale (ONS):|To assess whether singing improves (changes) further aspects of mental health, including anxiety, using the State-Trait Anxiety Scale (STAI)|To ascertain whether singing improves the observed mother-infant interaction using the Crittenden CARE-Index (CCI)|To ascertain whether singing improves the perceived mother-infant relationship using the Maternal Postpartum Attachment Scale (MPAS)|To ascertain whether singing improves the perceived mother-infant relationship using the Parent Reflective Functioning Questionnaire (PRFQ)|To ascertain whether singing improves social support and reduces loneliness using the UCLA Loneliness Scale|To ascertain whether singing improves social support and reduces loneliness using the Multidimensional Scale of Perceived Social Support (MSPSS)|To identify whether there are biological mechanisms underpinning the psychological outcomes assessed using changes in measurements in stress hormones, including hair cortisol, diurnal cortisol and salivary cytokines|To identify whether there are biological mechanisms underpinning the psychological outcomes assessed using changes in measurements in salivary oxytocin|To identify how the singing sessions affect the lived experience of mothers with PND using focus groups|To explore the phenomenology of PND and how singing intersects with PND among women with particular risk factors for PND (traumatic birth, adverse childhood experiences, and social isolation/loneliness) using semi-structured interviews|To assess the acceptability of the intervention using the Intervention Measure (AIM)|To assess reasons for perceived acceptability of the intervention using semi-structured interviews|To assess uptake/reach of the intervention using recruitment rate records|To assess the appropriateness of the intervention using Intervention Appropriateness Measure (IAM)|To assess the appropriateness of the intervention using semi-structured interviews|To assess the feasibility of the intervention using the Feasibility of Intervention Measure (FIM)|To assess the feasibility of the intervention using semi-structured interviews|To assess intervention adherence and attrition rates using attendance data (rates and drop out reasons)|To assess the adoption of the intervention using participants and stakeholder enrollment rates|To assess the cost effectiveness of the intervention using the 5-level EQ-5D version (EQ5D-5L)|To assess the cost effectiveness of the intervention using the Adult Service Use Schedule (AD-SUS)|To assess the cost effectiveness of the intervention using implementation activity logs (to estimate implementation costs).|To assess factors affecting the sustainability and scalability of the intervention using the NOMAD Scale:|To assess factors affecting the sustainability and scalability of the intervention using semi-structured interviews Female Not Applicable 400 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 219425/Z/19/Z-PND|278445 December 2023

Long, Y., et al. (2020). "Interventions for non-tubal ectopic pregnancy." Cochrane Database of Systematic Reviews 2020(7): CD011174.
	Background: Non-tubal ectopic pregnancy is the implantation of an embryo at a site lying outside the uterine cavity or fallopian tubes. Sites include a caesarean scar, the cornua uteri, the ovary, the cervix, and the abdomen. There has been an increasing trend in the occurrence of these rare conditions, especially caesarean scar pregnancy (CSP). Objective(s): To evaluate the clinical effectiveness and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy in terms of fertility outcomes and complications. Search Method(s): We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) search portal and nine other databases to 12 December 2019. We handsearched reference lists of articles retrieved and contacted experts in the field to obtain additional data. Selection Criteria: We included randomized controlled trials (RCTs) published in all languages that examined the effects and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy. Data Collection and Analysis: We used Cochrane standard methodological procedures. Primary outcomes were treatment success and complications. Main Result(s): We included five RCTs with 303 women, all reporting Caesarean scar pregnancy. Two compared uterine arterial embolization (UAE) or uterine arterial chemoembolization (UACE) plus methotrexate (MTX) versus systemic MTX and subsequent dilation and suction curettage; one compared UACE plus MTX versus ultrasonography-guided local MTX injection; and two compared suction curettage under hysteroscopy versus suction curettage under ultrasonography after UAE/UACE. The quality of evidence ranged from moderate to very low. The main limitations were imprecision (small sample sizes and very wide confidence intervals (CI) for most analyses), multiple comparisons with a small number of trials, and insufficient data available to assess heterogeneity. UAE/UACE versus systemic MTX prior to suction curettage. Two studies reported this comparison. One compared UAE with systemic MTX and one compared UACE plus MTX versus systemic MTX, in both cases followed by a suction curettage. We are uncertain whether UAE/UACE improved success rates after initial treatment (UAE: risk ratio (RR) 1.00, 95% CI 0.90 to 1.12; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.87, 95% CI 0.54 to 1.38; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced rates of complications (UAE: RR 0.47, 95% CI 0.13 to 1.75; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.62, 95% CI 0.26 to 1.48; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced adverse effects (UAE: RR 1.58, 95% CI 0.41 to 6.11; 1 RCT, 72 women; low-quality evidence; UACE: RR 1.16, 95% CI 0.32 to 4.24; 1 RCT, 28 women; low-quality evidence), and it was not obvious that the types of events had similar values to participants (e.g. fever versus vomiting). Blood loss was lower in UAE/UACE groups than systemic MTX groups (UAE: mean difference (MD) -378.70 mL, 95% CI -401.43 to -355.97; 1 RCT, 72 women; moderate-quality evidence; UACE: MD -879.00 mL, 95% CI -1135.23 to -622.77; 1 RCT, 28 women; moderate-quality evidence). Data were not available on time to normalize beta-human chorionic gonadotropin (beta-hCG). UACE plus MTX versus ultrasonography-guided local MTX injection. We are uncertain whether UACE improved success rates after initial treatment (RR 0.95, 95% CI 0.56 to 1.60; 1 RCT, 45 women; very low-quality evidence). Adverse effects: the study reported the same number of failed treatments in each arm (RR 0.88, 95% CI 0.40 to 1.92; 1 RCT, 45 women). We are uncertain whether UACE shortened the time to normalize beta-hCG (MD 1.50 days, 95% CI -3.16 to 6.16; 1 RCT, 45 women; very low-quality evidence). Data were not available for complications. Suction curettage under hysteroscopy versus under ultrasonography after UAE/UACE. Two studies reported this comparison One compared suction curettage under hysteroscopy versus under ultrasonography after UAE, and one compared these interventions after UACE. We are uncertain whether suction curettage under hysteroscopy improved success rates after initial treatment (UAE: RR 0.91, 95% CI 0.81 to 1.03; 1 RCT, 66 women; very low-quality evidence; UACE: RR 1.02, 95% CI 0.96 to 1.09; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced rates of complications (UAE: RR 4.00, 95% CI 0.47 to 33.91; 1 RCT, 66 women; very low-quality evidence; UACE: RR 0.18, 95% CI 0.01 to 3.72; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced adverse effects (UAE: RR 3.09, 95% CI 0.12 to 78.70; 1 RCT, 66 women; very low-quality evidence; UACE: not estimable; 1 RCT, 92 women; very low-quality evidence). We are uncertain whether suction curettage under hysteroscopy shortened the time to normalize beta-hCG (UAE: MD 4.03 days, 95% CI -1.79 to 9.85; 1 RCT, 66 women; very low-quality evidence; UACE: MD 0.84 days, 95% CI -1.90 to 3.58; 1 RCT, 92 women; low-quality evidence). Non-tubal ectopic pregnancy other than CSP. No studies reported on non-tubal ectopic pregnancies in locations other than on a caesarean scar. Authors' conclusions: For Caesarean scar pregnancies (CSP) it is uncertain whether there is a difference in success rates, complications, or adverse events between UAE/UACE and administration of systemic MTX before suction curettage (low-quality evidence). Blood loss was lower if suction curettage is conducted after UAE/UACE than after administration of systemic MTX (moderate-quality evidence). It is uncertain whether there is a difference in treatment success rates, complications, adverse effects or time to normalize beta-hCG between suction curettage under hysteroscopy and under ultrasonography (very low-quality evidence). There are no studies of non-tubal ectopic pregnancy other than CSP and RCTs for these types of pregnancy are unlikely.Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Longo, P. S., et al. (2019). "Urinary incontinence following subtotal and total hysterectomy: a systematic review." Einstein (Sao Paulo, Brazil) 17(2): eRW4320.
	OBJECTIVE: To evaluate the best surgical approach for the female urinary incontinence. METHOD(S): Systematic review conducted in MEDLINE Cochrane, EMBASE and LILACS database up to September 1st, 2017. Articles were selected according to study type, type of intervention and outcomes. Articles were selected by more than one researcher based on title, abstract and full text. The SIGN checklist was used for bias assessment. RESULT(S): A total of 165 articles were retrieved from MEDLINE . Twenty-five studies were elected for full text reading, and 11 of them were selected for the final text analysis. The heterogeneity between questionnaires used in different studies precluded a meta-analysis of results. CONCLUSION(S): This study yielded evidences supporting the hypothesis that total and subtotal hysterectomy have different impacts on urinary function of patients with benign uterine diseases. Articles revealed higher frequency of urinary incontinence following subtotal compared to total hysterectomy.

Longo, V., et al. (2019). "Strategies to improve cancer immune checkpoint inhibitors efficacy, other than abscopal effect: A systematic review." Cancers 11(4): 539.
	Despite that the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitourinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response such as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a higher expression of immune checkpoint molecules, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors in order to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve the response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitory receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.Copyright © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Łoniewski, I., et al. (2023). "Multispecies probiotic affects fecal short-chain fatty acids in postmenopausal women with obesity: A post hoc analysis of a randomized, double-blind, placebo-controlled study." Nutrition (Burbank, Los Angeles County, Calif.) 114: 112109.
	Objectives: Probiotics are known to regulate host metabolism. The aim of this study was to assess whether interventions with a multi-strain probiotic formula affect fecal short-chain fatty acids (SCFAs).; Methods: The analysis was carried out in 56 obese, postmenopausal women randomized to three groups: probiotic dose 2.5 × 10 9 CFU/d (n = 18; lower probiotic dose [LPD]), 1 × 10 10 CFU/d (n = 18; higher probiotic dose [HPD]), or placebo (n = 20).; Results: An increase in three SCFA fecal concentrations in the HPD group was observed: acetic acid (C2; effect [E] = 1.72, SE = 0.73; 95% confidence interval [CI], 0.28-3.16; P = 0.019), butyric acid (C4; E = 0.98, SE = 0.46; 95% CI, 0.08-1.88; P = 0.033), and valeric acid (C5; E = 0.68, SE = 0.23; 95% CI, 0.23-1.12; P = 0.003). The mediation analysis showed that the decrease in uric acid under HPD may be transmitted through the elevation of C5 content. Multi-strain probiotic increases the SCFA content in the stool in a dose-dependent manner, which may diminish some cardiovascular risk factors because of a reduction in blood uric acid levels.; Conclusion: Assessing long-term health benefits requires further research, including assessment of blood SCFA concentrations and multiomic and mechanistic approaches.; Competing Interests: Declaration of competing interest Mariusz Kaczmarczyk and Karolina Skonieczna-Żydecka receive remuneration from probiotic company. Igor Łoniewski in the probiotic company CEO. Other authors report no conflicts of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Loohuis, A. M. M., et al. (2022). "One year effectiveness of an app-based treatment for urinary incontinence in comparison to care as usual in Dutch general practice: A pragmatic randomised controlled trial over 12 months." BJOG: An International Journal of Obstetrics and Gynaecology 129(9): 1474-1480.
	Objective: To assess the long-term effectiveness of app-based treatment for female stress, urgency or mixed urinary incontinence (UI) compared with care-as-usual in primary care. Design(s): A pragmatic, randomised controlled, superiority trial. Setting(s): Primary care in the Netherlands from 2015 to 2018, follow up at 12 months. Population: Women with two or more UI episodes per week and access to mobile apps, wanting treatment. A total of 262 women were randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended 1 year follow up. Intervention(s): The standalone app included conservative management for UI with motivation aids (e.g. reminders). Care-as-usual was delivered according to the Dutch GP guideline for UI. Main Outcome Measure(s): Effectiveness assessed by the change in symptom severity score (ICIQ-UI-SF) and the change in quality of life (ICIQ-LUTSqol) with linear regression on an intention-to-treat basis. Result(s): Clinically relevant improvement of UI severity for both app (-2.17 +/- 2.81) and care-as-usual (-3.43 +/- 3.6) groups, with a non-significant mean difference of 0.903 (-0.66 to 1.871). Conclusion(s): App-based treatment is a viable alternative to care-as-usual for UI in primary care in terms of effectiveness after 1 year. Tweetable abstract: App-based treatment for female urinary incontinence is a viable alternative to care-as-usual after 12 months.Copyright © 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.

López Claudia, C., et al. (2023). "Metronidazole for Prevention of Pelvic Cellulitis and Abscess after Laparoscopic Hysterectomy: A Triple-blinded, Randomized, Placebo-controlled Clinical Trial." Journal of Minimally Invasive Gynecology 30(11): 912-918.
	Study Objective: To determine whether a postoperative 5-day treatment schedule with vaginal metronidazole added to conventional antibiotic prophylaxis with 2 g cefazolin modifies the risk of pelvic cellulitis (PC) and pelvic abscess (PA) after total laparoscopic hysterectomy (TLH).; Design: A randomized, controlled, triple-blind, multicenter clinical trial.; Setting: Two centers dedicated to minimally invasive gynecologic surgery in Colombia.; Patients: A total of 574 patients were taken to TLH because of benign diseases.; Intervention: Patients taken to TLH were divided into 2 groups (treatment group, cefazolin 2 g intravenous single dose before surgery + metronidazole vaginal ovules for 5 days postoperatively, control group: cefazolin 2 g intravenous single dose + placebo vaginal ovules for 5 days postoperatively).; Measurements and Main Results: The absolute frequency (AF) of PC and PA and their relationship with the presence of bacterial vaginosis (BV) were measured. There was no difference in AF of PC (AF, 2/285 [0.7%] vs 5/284 [1.7%] in the treatment and placebo groups, respectively; risk ratio, 1.75; 95% confidence interval, 0.54-5.65; p = .261), nor for PA (AF, 0/285 [0%] vs 2/289 [0.7%]; p = .159, in the treatment and placebo groups, respectively). The incidence of BV was higher in the metronidazole group than the placebo group (42.5% vs 33.4%, p = .026).; Conclusion: The use of vaginal metronidazole ovules during the first 5 days in postoperative TLH added to conventional cefazolin prophylaxis does not prevent the development of PC or PA, regardless of the patient's diagnosis of BV. (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

López-Liria, R., et al. (2021). "Efficacy of Physiotherapy Treatment in Primary Dysmenorrhea: A Systematic Review and Meta-Analysis." International Journal of Environmental Research and Public Health 18(15).
	Primary dysmenorrhea (PD) refers to painful cramps before and/or during menstruation. There is a need for emphasis on alternative methods of conservative treatment, so as to reduce the dependence on drugs for alleviating the symptoms. The aim was to find out the effectiveness of some physiotherapy techniques in the treatment of PD. A systematic review and meta-analysis was conducted according to PRISMA standards. The descriptors were "dysmenorrhea", "physical the-rapy", "physiotherapy", and "manual therapy". The search was performed in five databases: Scopus, PubMed, PEDro, Web of Science, and Medline, in February 2021. The inclusion criteria were randomized controlled trials over the last six years. Articles not related to the treatment of PD or using pharmacology as the main treatment were excluded. Nine articles met the objectives and criteria, with a total of 692 participants. The most used scale to measure pain was the VAS (visual analogue scale). The main techniques were isometric exercises, massage therapy, yoga, electrotherapy, connective tissue manipulation, stretching, kinesio tape, progressive relaxation exercises and aerobic dance. Meta-analysis shows benefits of physiotherapy treatment for pain relief compared with no intervention or placebo (MD: -1.13, 95% CI: -1.61 to -0.64, I 2 : 88%). The current low-quality evidence suggests that physiotherapy may provide a clinically significant reduction in menstrual pain intensity. Given the overall health benefits of physiotherapy and the low risk of side effects reported, women may consider using it, either alone or in conjunction with other therapeutic modalities.

López-Liria, R., et al. (2019). "Effectiveness of Physiotherapy Treatment for Urinary Incontinence in Women: A Systematic Review." Journal of women's health (2002) 28(4): 490-501.
	BACKGROUND: Urinary incontinence (UI) may be defined as involuntary urine loss, which can be diagnosed based on patient-reported measures and is a hygiene and social problem in those who have it, affecting their quality of life negatively. OBJECTIVE: The study aimed to determine the effectiveness of distinct physiotherapy techniques used in the treatment of UI in women through a systematic review of the existing literature. The scales and instruments used for the assessment and follow-up of UI were described. METHODS: On searching the PubMed, Dialnet, PEDro, and SciELo databases, 16 articles, with information on 1220 patients that comply with the inclusion criteria and conform to the proposed objectives were obtained, limiting the publication period to 2007-2016. The PRISMA statement was adopted. RESULTS: The "Pad Test" is a commonly used diagnostic test and bladder diaries on paper; the Oxford scale was used in the assessment of pelvic floor muscle strength. Distinct protocols and techniques have been described in the treatment of UI in women, namely, pelvic floor exercises, vaginal cones, biofeedback, and electrostimulation. Upon analysis of the content of the articles, the quality of the included clinical trials was determined using the PEDro scale. CONCLUSIONS: Studies included in this work propose that physiotherapy treatment may improve UI, the patients' quality of life, and social relations in women. It is necessary to establish group treatment protocols for women with UI, supervised by a physiotherapist to reduce the financial burden incurred from this health problem.

Lopez-Moreno, A. and M. Aguilera (2020). "Probiotics dietary supplementation for modulating endocrine and fertility microbiota dysbiosis." Nutrients 12(3): 757.
	Human microbiota seems to play a key role in endocrine and reproductive systems. Fortunately, microbiota reproductive dysbiosis start to be treated by probiotics using typical species from genus Lactobacillus. This work presents the compiled and analysed results from the most up-to-date information from clinical trials regarding microbiota, fertility, probiotics and oral route administration, reviewing open access scientific documents. These studies analyse the clinical impact of probiotics administered on several endocrine disorders' manifestations in women: mastitis; vaginal dysbiosis; pregnancy complication disorders; and polycystic ovary syndrome. In all cases, the clinical modulation achieved by probiotics was evaluated positively through the improvement of specific disease outcomes with the exception of the pregnancy disorders studies, where the sample sizes results were statistically insufficient. High amounts of studies were discarded because no data were provided on specific probiotic strains, doses, impact on the individual autochthon microbiota, or data regarding specific hormonal values modifications and endocrine regulation effects. However, most of the selected studies with probiotics contained no protocolised administration. Therefore, we consider that intervention studies with probiotics might allocate the focus, not only in obtaining a final outcome, but in how to personalise the administration according to the disorder to be palliated.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Lor, K. Y., et al. (2020). "Does pre-operative urodynamics lead to better outcomes in management of urinary incontinence in women? A linked systematic review and meta-analysis." European Journal of Obstetrics and Gynecology and Reproductive Biology 244: 141-153.
	The use of preoperative urodynamics as a standard investigation for urinary incontinence (UI) has long been a subject of debate, with a lack of robust evidence to demonstrate improved patients' outcomes. We aim to compare the clinical and cost effectiveness of urodynamics versus office clinical evaluation only, prior to the treatment of UI. We conducted three linked systematic reviews and meta-analyses of randomised controlled trials (RCTs) comparing urodynamics assessment versus clinical evaluation only in women prior to 1) non-surgical treatment of UI, 2a) surgical treatment of stress urinary incontinence (SUI) and 2b) invasive treatment for overactive bladder (OAB). Women with severe pelvic organ prolapse, previous continence surgery and neuropathic bladder were excluded. Primary outcomes were patient-reported and objective success post-treatment. Secondary outcomes were adverse events, quality of life, sexual function and health economic measures. We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases for each category, which was last updated on January 2019. Study selection, risk of bias assessment and data extraction were performed independently by two reviewers. The random effects model was used to assess risk ratio and mean difference with 95% confidence interval. Statistical heterogeneity was assessed by I2 statistics and the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Four RCTs compared urodynamics versus clinical evaluation only prior to non-surgical management of UI. Treatment consisted of pelvic floor muscle training, with or without pharmacological therapy. Meta-analysis of 150 women showed no evidence of significant difference in the patient-reported and objective success rates between groups (P = 0.520, RR: 0.91, 95% Cl 0.69-1.21, I2 = 0% and P = 0.470, RR:0.87, 95% Cl 0.59-1.28, I2 = n/a, respectively). Seven RCTs were identified for surgical management of SUI. The majority of women underwent mid-urethral tape procedures (retropubic or transobturator approach). Meta-analysis of 1149 women showed no evidence of significant difference in patient-reported (P = 0.850, RR:1.01, 95% CI 0.88-1.16, I2 = 53%) and objective success between groups (P = 0.630, RR:1.02, 95% CI 0.95-1.08, I2 = 28%). There was no significant difference in incidence of voiding dysfunction, de novo urgency, and urinary tract infection between groups. No RCTs were identified for invasive management of OAB. In conclusion, limited evidence shows that routine urodynamics prior to non-surgical management of UI or surgical management of SUI is not associated with improved treatment outcomes, when compared to clinical evaluation only. Well-designed clinical trials are needed to evaluate the clinical and cost-effectiveness of routine urodynamics prior to surgical management of SUI and OAB.Copyright © 2019 Elsevier B.V.

Lorenz, J. (2021). "Radical trachelectomy for early stage cervical cancer." Geburtshilfe und Frauenheilkunde 81(1): 14.
	Google Translate: "Many women with early-stage cervical cancer opt for fertility-preserving surgery. What surgical and oncological outcome can patients expect after radical trachelectomy and pelvic lymphonodectomy? How does a later pregnancy progress? And to what extent does the surgical technique influence these results? US researchers investigated these questions."

Lorenz, J. (2022). "Fibroids: Cost-effectiveness of uterine artery embolization and myomectomy." Geburtshilfe und Frauenheilkunde 82(1): 13.
	
Loring, M., et al. (2021). "A Systematic Review of Adenomyosis: It Is Time to Reassess What We Thought We Knew about the Disease." Journal of Minimally Invasive Gynecology 28(3): 644-655.
	Objective: To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. Data Sources: Systematic review of PubMed between January 1972 and April 2020. Search strategy included: "adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea[text word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text Word] OR imaging diagnosis [Text Word] OR pathology[Text Word]. Methods of Study Selection: Articles published in English that addressed adenomyosis and discussed prevalence, diagnosis, and symptoms were included. The included articles described pathology diagnosis, imaging, biopsy diagnosis, prevalence and age of onset, symptoms, and concomitant endometriosis. Tabulation, Integration, and Results: Sixteen articles were included in the qualitative analysis. The studies are heterogeneous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. The prevalence estimates range from 20% to 88.8% in women who are symptomatic (average 30%-35%), with most diagnosed between the ages of 32 years and 38 years. The correlation between imaging and pathology continues to evolve. As imaging advances, newer studies report that younger women who are symptomatic are being diagnosed with adenomyosis on the basis of both magnetic resonance imaging and/or transvaginal ultrasound. High rates of concomitant endometriosis create challenges when discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by adenomyosis. Conclusion(s): Adenomyosis remains a challenge to identify, assess, and research because of the lack of standardized diagnostic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adenomyosis. The priority should be to create standardized histopathologic and imaging diagnoses to gain a deeper understanding of adenomyosis.Copyright © 2020 AAGL

Lorusso, D., et al. (2023). "Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice." European journal of cancer (Oxford, England : 1990) 186: 172-184.
	Purpose: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported.; Patients and Methods: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m 2 Q3W or paclitaxel 80 mg/m 2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints.; Results: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales.; Conclusion: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC.; Clinicaltrials: GOV: NCT03517449.; Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Domenica Lorusso: Advisory Board: GSK, AstraZeneca, MSD, Clovis Oncology, PharmaMar, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Funding (inst.): MSD, Clovis Oncology, GSK, PharmaMar, AstraZeneca, Seagen, Genmab, Immogen, Incyte, Novartis, Roche; Invited Speaker: Genmab, PharmaMar, MSD; Principal Investigator: AstraZeneca, MSD, Genmab, Immunogen, Clovis, Roche, Incyte; Board of Directors: GCIG Nicoletta Colombo: Honoraria: Amgen, AstraZeneca, Clovis Oncology, Eisai, GlaxoSmithKline, Immunogen, mersana, MSD Oncology, Novartis, Pfizer, PharmaMar, Roche/Genentech, Tesaro; Consulting or Advisory Role: AstraZeneca, BioCad, Clovis Oncology, Eisai, GlaxoSmithKline, Immunogen, Mersana, MSD Oncology, Pfizer, PharmaMar, Roche/Genentech, Tesaro Antonio Casado Herraez: advisory boards for AstraZeneca, Clovis Oncology, Eisai, Merck, PharmaMar; some support for attending major international oncological conferences (virtually or face to face meetings) from PharmaMar, Lilly, Roche, AstraZeneca-Merck and GSK; Research support (institution): PharmaMar Alessandro Santin: grants from Puma, Immunomedics, Gilead, Synthon, Merck, Boehringer-Ingelheim, Genentech, Tesaro, Eisai; personal fees from Merck, Tesaro, Eisai Emeline Colomba: Honoraria: Bristol Myers Squibb, GlaxoSmithKline, Ipsen, Merck; Travel, Accommodations, Expenses: Bristol Myers Squibb, Ipsen, Pfizer David Scott Miller: Advisory Board: Eisai, Karyopharm, Tesaro, Tarveda, Myriad, GlaxoSmithKline, AbbVie, AstraZeneca, EMD Serono, Seagen; Board of Directors/Leadership Role: NRG Oncology; Research Grant: NRG Oncology, Karyopharm, Advaxis, Immunogen, Advenchen, Regeneron, Merck, Agenus, Akesobio, EMD Serono Keiichi Fujiwar : Honoraria: Chugai Pharma, Daiichi Sankyo, Eisai, Kyowa Hakko Kirin, Nippon Kayaku, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Zeria Pharmaceutical; Consulting or Advisory Role: Abbvie, AstraZeneca, Eisai, Genmab, MSD, Pfizer, Taiho Pharmaceutical, Takeda; Research Funding (institution): AstraZeneca, Chugai Pharma, Eisai, Genmab, Immunogen, Kaken Pharmaceutical, Lilly, MSD, Oncotherapeutics, Ono Pharmaceutical, Regeneron, Shionogi, Zeria Pharmaceutical; Travel, Accommodations, Expenses: Abbvie, MSD, Pfizer; Consulting or Advisory Role - Abbvie; AstraZeneca; Eisai; Genmab; MSD; Pfizer; Taiho Pharmaceutical; Takeda; Research Funding - AstraZeneca (Inst); Chugai Pharma (Inst); Eisai (Inst); Genmab (Inst); Immunogen (Inst); Kaken Pharmaceutical (Inst); Lilly (Inst); MSD (Inst); Oncotherapeutics (Inst); Ono Pharmaceutical (Inst); Regeneron (Inst); Shionogi (Inst); Zeria Pharmaceutical (Inst); Travel, Accommodations, Expenses - Abbvie; MSD; Pfizer Sandro Pignata: Honoraria: AstraZeneca, MSD, Pfizer, PharmaMar, Roche, Tesaro; Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Pfizer, PharmaMar, Roche, Tesaro; Research Funding (institution) AstraZeneca, MSD, Pfizer, Roche Sally E. Baron-Hay: Consultancy fees: Eisai, Merck Sharp and Dohme (Australia Pty Ltd), Pfizer, AstraZeneca Australia; Honoraria: Amgen, Novartis Pharmaceuticals Australia Pty Ptd, Eli Lilly Australia, Roche, Merck Sharp and Dohme (Australia Pty Ltd) Isabelle Laure Ray-Coquard: Honoraria: Abbvie, Advaxis, Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, DECIPHERA, Genmab, GlaxoSmithKline, MERSANA, MSD Oncology, OxOnc, Pfizer, PharmaMar, Roche, Tesaro; Consulting or Advisory Role: Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Deciphera, Genmab, GlaxoSmithKline, Mersana, MSD Oncology, Pfizer, PharmaMar, Roche, Tesaro; Research Funding: BMS, MSD Oncology; Travel, Accommodations, Expenses: Advaxis, AstraZeneca, BMS, Clovis Oncology, GlaxoSmithKline, PharmaMar, Roche, Tesaro Ronnie Shapira-Frommer: Honoraria: AstraZeneca, Bristol Myers Squibb, Medison, MSD, NeoPharm, Novartis, Roche; Consulting or Advisory Role: MSD, VBL Therapeutics; Research Funding: MSD Yong Man Kim: Stock and Other Ownership Interests: Genolution, Johnson & Johnson; Research Funding: Regeneron, Roche Mary McCormack: Research Funding (institution): Roche/Genentech; Travel, Accommodations, Expenses: Roche; honoraria from GSK, AZ, and Eisai. Rachid Massaad: Full-time employee of MSD Europe Allison Martin Nguyen: Full-time employee/stock ownership: Merck & Co., Inc. Qi Zhao: Full time employee of Eisai Inc. Jodi McKenzie: Full time employee of Eisai Inc. Vimalanand S. Prabhu: Full-time employee/stock ownership: Merck & Co., Inc.; Travel, Accommodations, Expenses: Merck & Co., Inc Vicky Makker: study support (all funding to institution) / consultancy / advisory board membership from AstraZeneca, Clovis, Eisai, Faeth, Genentech, GSK, iTEOS, Karyopharm, Moreo, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Takeda, Zymeworks; Dr Makker is supported in part by the NIH/NCI Cancer Center Support Grant P30 CA008748. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lorusso, D., et al. (2023). "Updated progression-free survival and final overall survival with maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	OBJECTIVE: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. METHOD(S): Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status. RESULT(S): Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. CONCLUSION(S): This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.Copyright © IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.

Loscalzo, Y., et al. (2023). "Premature Triadic Music Therapy (PT-MT) for babies and their parents: a pilot study." Journal of Reproductive and Infant Psychology 41(2): 193-212.
	Objective: We aim to test the feasibility and effectiveness of Premature Triadic Music Therapy (PT-MT) in the premature baby unit.; Methods: The design was a clinical pre-test-post-test trial with a convenience sample. Inclusion criteria were a gestational age higher than 28 weeks for preterm infants and the absence of shock or extreme distress for parents. Six preterm children (with a gestational age of 33 to 36 weeks) and their parents participated in the study. For the children, we measured heart rate, blood perfusion, and blood saturation at three different times (pre-PT-MT, during PT-MT, after PT-MT) as quantitative indicators of distress. Their parents completed the Edinburgh Postnatal Depression Scale (EPDS) before and after the PT-MT intervention.; Results: We found a statistically significant lower heart rate and a marginally statistically significant higher blood perfusion during PT-MT, as compared to the baseline. However, these changes were not present at the end of PT-MT. The parents' EPDS scores were not statistically significantly lower at the post-test, although, the Medians of the scores did decrease.; Conclusions: PT-MT is a promising intervention for the reduction of distress in both parents and children. Further studies should include a higher number of sessions and participants.

Lossl, K., et al. (2020). "Biological and Clinical Rationale for Androgen Priming in Ovarian Stimulation." Frontiers in Endocrinology 11: 627.
	Androgen receptors are expressed by all stages of growing follicles, and follicular fluid androgen levels are positively correlated to granulosa cell androgen receptor and follicle-stimulating hormone (FSH) receptor expression. Thus, androgens may promote follicular growth, accumulation and/or responsiveness to gonadotropins. This is explored therapeutically in the concept of androgen priming, to improve the ovarian response to stimulation in assisted reproduction. Androgen effects may be achieved in two different ways, either directly by providing exogenous androgen or by providing luteinizing hormone (LH) activity [i.e., LH or human chorionic gonadotropin (hCG)] to stimulate local ovarian production of androgen. The androgen concentrations in follicular fluid by far exceed the levels in female circulation and it has recently been shown that there was no correlation between serum testosterone levels and follicular fluid androgen levels. There is some evidence that administration of exogenous dehydroepiandrosterone or testosterone increases live birth rates, but an optimal protocol has not been established and such adjuvant treatment should be considered experimental. Furthermore, studies exploring long-term administration of LH activity, achieving LH levels comparable to those seen in women with polycystic ovary syndrome, are awaited. The aim of the present review is to discuss critically the most suitable approach for androgen priming from a biological and clinical standpoint, and to evaluate current approaches and results obtained in clinical trials.© Copyright © 2020 Lossl, Freiesleben, Wissing, Birch Petersen, Holt, Mamsen, Anderson and Andersen.

Loughnan, S. A., et al. (2022). "Living with Loss: study protocol for a randomized controlled trial evaluating an internet-based perinatal bereavement program for parents following stillbirth and neonatal death." Trials 23(1): 464.
	Background: Stillbirth and neonatal death are devastating pregnancy outcomes with long‐lasting psychosocial consequences for parents and families, and wide‐ranging economic impacts on health systems and society. It is essential that parents and families have access to appropriate support, yet services are often limited. Internet‐based programs may provide another option of psychosocial support for parents following the death of a baby. We aim to evaluate the efficacy and acceptability of a self‐guided internet‐based perinatal bereavement support program “Living with Loss” (LWL) in reducing psychological distress and improving the wellbeing of parents following stillbirth or neonatal death. Methods: This trial is a two‐arm parallel group randomized controlled trial comparing the intervention arm (LWL) with a care as usual control arm (CAU). We anticipate recruiting 150 women and men across Australia who have experienced a stillbirth or neonatal death in the past 2 years. Participants randomized to the LWL group will receive the six‐module internet‐based program over 8 weeks including automated email notifications and reminders. Baseline, post‐intervention, and 3‐month follow‐up assessments will be conducted to assess primary and secondary outcomes for both arms. The primary outcome will be the change in Kessler Psychological Distress Scale (K10) scores from baseline to 3‐month follow‐up. Secondary outcomes include perinatal grief, anxiety, depression, quality of life, program satisfaction and acceptability, and cost‐effectiveness. Analysis will use intention‐to‐treat linear mixed models to examine psychological distress symptom scores at 3‐month follow‐up. Subgroup analyses by severity of symptoms at baseline will be undertaken. Discussion: The LWL program aims to provide an evidence‐based accessible and flexible support option for bereaved parents following stillbirth or neonatal death. This may be particularly useful for parents and healthcare professionals residing in rural regions where services and supports are limited. This RCT seeks to provide evidence of the efficacy, acceptability, and cost‐effectiveness of the LWL program and contribute to our understanding of the role digital services may play in addressing the gap in the availability of specific bereavement support resources for parents following the death of a baby, particularly for men. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12621000631808. Registered prospectively on 27 May 2021.

Loughnan, S. A., et al. (2019). "Internet-delivered psychological interventions for clinical anxiety and depression in perinatal women: a systematic review and meta-analysis." Archives of Women's Mental Health 22(6): 737-750.
	Perinatal anxiety and depression are common and associated with negative outcomes if left untreated. Internet-delivered treatments can improve treatment accessibility and have demonstrated effectiveness in treating anxiety and depression in the general adult population. However, little is known about how effective and acceptable these interventions are for perinatal women. This paper describes a systematic review and preliminary meta-analysis of internet-delivered psychological interventions for the treatment of clinical anxiety and depression in perinatal women. A systematic search was carried out of seven electronic databases. Seven studies evaluating six distinct internet-delivered psychological interventions were identified. Of the seven studies included, two were open trials and five were randomized controlled trials with a total of 595 participants. Preliminary findings indicate large improvements in depression (Hedges g = 1.67; 95% CI 1.38-1.96) and anxiety (Hedges g = 1.08; 95% CI 0.80-1.36) from pre- to post-treatment. However, between-group differences between interventions and control conditions were only moderate for depression (Hedges g = 0.60; 95% CI 0.43-0.78) and anxiety (Hedges g = 0.54; 95% CI 0.24-0.85). While our preliminary findings are promising, this review identifies an area of research still in its early stages with significant gaps in the literature that need to be addressed. Further research is needed to establish the efficacy and acceptability of these interventions in this population, especially for antenatal depression and anxiety disorders.Copyright © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.

Louisville University, o. (2024). Vaginal Baclofen Suppositories in Chronic Pelvic Pain.
	No Results Available Drug: 20 mg baclofen vaginal suppository daily per vagina|Drug: Placebo Visual analogue Score (VAS) 1-100 for pain|Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference score|Pelvic floor impact questionnaire|Pelvic floor disability index (PFDI) questionnaire|O'Leary Sant questionnaire|Patient-Reported Outcomes Measurement Information System (PROMIS) global health score|Overall Satisfaction|Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual function score|Number of other treatments for chronic pelvic pain during the trial period|Pill Count Female Phase 2 44 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 22.1000 June 1, 2025

Lourenço Danilo, B., et al. (2023). "Urodynamic profile of voiding in patients with pelvic organ prolapse after surgery: a systematic review with meta-analysis." International Urogynecology Journal 34(1): 53-65.
	Introduction and Hypothesis: Pelvic organ prolapse (POP) is a defect of the female pelvic floor. Stress urinary incontinence (SUI), urge urinary incontinence (UUI), and obstructive symptoms may occur in these patients. The objective of surgical treatment is to restore the anatomy and function of the pelvic floor; however, it may prompt urinary symptoms not present previously. We performed a systematic review and meta-analysis to determine urodynamic changes in patients undergoing surgical correction for POP.; Methods: PubMed and Cochrane databases were searched for studies that contained data from urodynamic evaluation before and after vaginal surgery for POP. The main urodynamic data collected were free uroflowmetry (maximum flow [Qmax], voided volume, and post-void residual volume [PVR]), cystometry (bladder capacity, presence of detrusor overactivity [DO], SUI or UUI, and Valsalva leak point pressure), and pressure × flow study (detrusor pressure at maximum flow [PdetQmax], Qmax, and PVR).; Results: A total of 22 studies were included (1,549 women). Patients had a significantly higher prevalence of DO before surgery (OR = 1.56; 95% CI = 1.06-2.29), and surgeries without sling placement demonstrated a tendency to ameliorate DO. Patients who did not receive a sling were more incontinent after surgery. Bladder-emptying parameters improved after surgery, with higher PdetQmax before surgery (IV = 3.23; 95% CI = 0.45-1.18). Patients who did not receive MUS presented a lower Qmax (IV = -3.19; 95%CI = -4.09 to -2.30) and a higher PVR (IV = 27.89; 95%CI = 15.68-40.1) before surgery.; Conclusion: Correction surgery for POP yields better urodynamic emptying parameters, with a reduction in the prevalence of DO. In contrast, sling placement enhances obstructive parameters. (© 2022. The International Urogynecological Association.)

Loverix, L., et al. (2023). "PARP inhibitor predictive value of the Leuven HRD test compared with Myriad MyChoice CDx PLUS HRD on 468 ovarian cancer patients from the PAOLA-1/ENGOT-ov25 trial." European Journal of Cancer 188: 131-139.
	Background: The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]). Patients and Methods: The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53. We compared the predictive value of the Leuven HRD versus Myriad HRD test for PFS and OS in the randomised PAOLA-1 trial. Result(s): 468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven versus Myriad HRD status was 95%/86%/91%, respectively. Tumours were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5 years PFS (5yPFS) was 48.6% versus 20.3% (HR 0.431; 95% confidence intervals (CI) 0.312-0.595) for olaparib versus placebo, respectively (Myriad test 0.409; 95% CI 0.292-0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% versus 12.6% (HR 0.497; 95% CI 0.316-0.783), and 43.6% versus 13.3% (HR 0.435; 95% CI 0.261-0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% versus 54.4% (HR 0.663; 95% CI 0.442-0.995) for the Leuven test, and 68.0% versus 51.8% (HR 0.596 95% CI 0.393-0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively. Conclusion(s): A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumours, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test.Copyright © 2023 Elsevier Ltd

Loverro, G., et al. (2021). "Myomectomy during pregnancy: an obstetric overview." Minerva Obstetrics and Gynecology 73(5): 646-653.
	INTRODUCTION: Uterine fibroids (UFs) are the most common benign disease affecting female reproductive system, and occurring in 20-40% of women, and in 10% of pregnancies. The aim of the investigation was to summarize evidence about the management and treatment of UFs and related complications in pregnancy. EVIDENCE ACQUISITION: A literature review was performed using scientific databases, including all case report and case series, using a combination of key words related to the problem exposed. Data about gestational age at diagnosis, maximum fibroids diameter, type of surgery and gestational age at surgery, delivery and perinatal outcome were collected. Two clinical cases were also included. EVIDENCE SYNTHESIS: Sixty-six articles were selected, and 199 patients were included. In 76% of patients the gestational age at myomectomy was lower than 20 weeks, in 85% laparotomic surgery was chosen, in 41% of cases the maximum fibroid diameter was between 7-20 cm, in 41% of pregnancies the route of delivery was the Cesarean section. In the eight percent of cases there was a complication given by miscarriage, fetal demise or neonatal death. CONCLUSIONS: Myomectomy is a feasible procedure in those pregnancies complicated by symptomatic fibroids, though surgery in pregnancy is associated with an increased risk of obstetric complications.

Lowenstein, L., et al. (2022). "Conventional vaginal approach vs. transvaginal natural orifice transluminal endoscopic surgery for treating apical prolapse, a randomized controlled study." International Urogynecology Journal 33(Supplement 1): S152.
	Introduction: Vaginal hysterectomy combined with uterosacral ligament suspension (USLS) is one of the most common and effective surgeries for treating pelvic organ prolapse. Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) is becoming a more widespread approach for treating various gynecological and non-gynecological pathologies. No randomized controlled study has compared conventional vaginal hysterectomy to the vNOTES approach. Objective(s): To compare the outcomes of two surgical vaginal approaches to treat pelvic organ prolapse: the conventional vaginal hysterectomy combined with USLS and vNOTES hysterectomy plus USLS. Method(s): This multi-center randomized controlled trial was performed between November 2019 and May 2021 at Rambam Health Care Campus (Israel) and Imelda Hospital (Belgium). Thirty women underwent vNOTES procedures and 30 women underwent conventional vaginal procedures. The primary outcome was total surgical time. Secondary outcomes included hysterectomy time, USLS time, intraoperative bleeding, length of hospitalization, pain during the first 24 hours postoperative, the need for analgesia, intraoperative and postoperative adverse events, and patient-reported outcomes questionnaires. Parametric statistical methods were used to analyze the data. Result(s): Compared to conventional vaginal procedures, vNOTES procedures were shorter in total surgical time (77 vs. 93 min, pv=0.004), hysterectomy time (26 vs 33 min, pv<0.001), and USLS time (20 vs 26 min. pv=0.02). Blood loss was higher in conventional vaginal than vNOTES surgeries, as reflected by the mean blood loss estimate (143 vs 60 ml. pv<0.001) and the deltahemoglobin (pre-operation minus the post-operation hemoglobin level (1.8 vs 1.2 ml/dL, pv=0.01). Analgesics use, postoperative pain, surgical objective outcomes, and scores on patient-reported outcomes questionnaires were not different between the two groups. Adverse events were significantly more frequent in the conventional vaginal than in the vNOTES group (pv<0.001 for intraoperative events and pv=0.05 for events that occurred in the follow-up time interval). Conclusion(s): vNOTES USLS is non-inferior to conventional vaginal hysterectomy USLS in terms of surgical time, bleeding, and adverse events. Other surgical objective and subjective outcomes were similar between the approaches.

Łoziński, T., et al. (2021). "Oxytocin and Misoprostol With Diclofenac in the Preparation for Magnetic Resonance-Guided High-Intensity Ultrasound Treatment of Symptomatic Uterine Fibroids: A Prospective Cohort Study." Ultrasound in medicine & biology 47(6): 1573-1585.
	Uterine fibroids (UFs) are very common benign tumors of the female reproductive tract. According to recent reports, magnetic resonance-guided high-intensity ultrasound (MR-HIFU) appears to be a well-tolerated and efficient treatment option for UFs. However, MR-HIFU still presents several limitations. The treatment is rarely associated with achieving complete non-perfused volume (NPV). Not all patients are qualified for a final procedure, and selected women obtain very good results in such treatment. The primary objective of this experimental study was to assess the effect of transvaginal misoprostol and intravenous oxytocin preparation on UF volume change, sonication time and NPV after MR-HIFU procedure in women of reproductive age with symptomatic UFs. Secondary outcomes included the effect on the peri-procedural effectiveness of misoprostol and oxytocin. This study enrolled 247 women with symptomatic UFs; based on gynecologic examinations and magnetic resonance imaging (MRI) scans, 128 women qualified for MR-HIFU without pharmacologic treatment, 57 women qualified for the misoprostol/diclofenac group and 62 women qualified for the oxytocin group. Pharmacologic pre-treatment improved NPV compared with non-pharmacologic treatment (average NPV: controls 61.9% ± 25.8%; oxytocin 76.8% ± 20.7%; misoprostol/diclofenac 85.2% ± 15.1%; average sonication time: controls 120 min ± 56.4%; oxytocin 111 min ± 45.4%; misoprostol/diclofenac 80 min ± 47.7%). Statistical analysis did not reveal significant intergroup differences in UF volume changes after 6 mo (controls: n = 40, 37.4% ± 27.5%; oxytocin n = 25, 45.8% ± 31%; misoprostol/diclofenac n = 19, 33.4% ± 23.2%). The misoprostol/diclofenac group, which achieved the highest NPV immediately after the MR-HIFU procedure, was characterized by the lowest UF volume change percentages 6 mo later. The administration of vasoconstrictor drugs (oxytocin and misoprostol/diclofenac) to support MR-HIFU in UF treatment is a new issue that may improve the total effectiveness of this method. Randomized controlled trials are necessary to estimate the real effect of vasoconstrictors on MR-HIFU.

Ltd, R. D. C. C. P. (2023). Effectiveness of PEA Compared to Placebo on Acute Menstrual Pain.
	No Results Available Drug: Levagen+|Drug: Microcrystalline cellulose Change in acute menstrual pain severity, analgesic effect via Numeric Rating Scale (NRS)|Change in categorical pain levels via categorical pain relief scale|Effectiveness of the Treatment via Global Satisfaction scale of the Treatment Satisfaction Questionnaire for Medication (TSQM)|Change in rescue medication use via self-report|Safety of Use Female Phase 4 80 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment PEAMPS-23 August 1, 2025

Lu, C., et al. (2019). "Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: a meta-analysis of randomized controlled trials." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 32(8): 1299-1311.
	Objective: This study was designed to evaluate the efficacy of aspirin or heparin or both in the treatment for recurrent spontaneous abortion (RSA) in women with antiphospholipid antibody syndrome (APS).; Methods: Systematic searches for randomized clinical trials (RCTs) evaluating on live birth and preterm delivery, preeclampsia, intrauterine growth restriction, gestational diabetes, bleeding of RSA with APS patients receiving aspirin, and heparin therapy were carried out, from PubMed, EMBASE, ScienceDirect, and CNKI. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Relative risk (RR) and its 95% confidence interval were calculated.; Results: Nineteen publications with randomized controlled trials were selected for this study, which included a total of 1251 pregnant patients with diagnosis of RSA with APS. With respect to live birth, it was remarkably improved in aspirin plus heparin or heparin alone group [RR =1.23, 95% CI (1.12-1.36), p < .0001; RR = 1.18, 95% CI (1.03-1.35), p = .02]; aspirin alone group, however, there was no statistically significant difference compare to placebo [RR = 0.97, 95% CI (0.80-1.16), p = .71]. Meanwhile, aspirin plus heparin therapy did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications including preterm birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor bleeding. A beneficial therapeutic effect of heparin alone therapy was found on preventing preterm birth and low-dose aspirin plus heparin therapy was significant reduce the risk of preeclampsia.; Conclusion: An improvement of pregnancy outcomes in women with RSA and APS can be achieved by treatment strategies combining low-dose aspirin plus heparin or heparin alone. Aspirin alone, by contrast, seemed inferior to other treatments in achieving more live birth.

Lu, J., et al. (2021). "Meta-analysis of Perinatal Pelvic Floor Muscle Training on Urinary Incontinence." Western journal of nursing research 43(6): 597-605.
	This study was to evaluate the effect of pelvic floor muscle training (PFMT) on urinary incontinence (UI) in prenatal and postnatal women. The relevant literatures were searched from Pubmed, Embase, Cochrane Library, and Web of Science until January 20, 2020. Meta-analysis was performed with STATA 15.1 and the Begg's test was used for the publication bias. Results of the meta-analysis demonstrated that the rate of UI in the intervention group was lower than that in the control group [relative risk (RR): 0.712, 95%confidence intervals (CI): 0.622-0.816, P<0.001); the strength of pelvic floor muscle in the intervention group was higher than that in the control group [weighted mean difference (WMD): 8.448, 95%CI: 2.300-14.595, P=0.007); and the urine leakage measured by the urinal pad in the intervention group was less than that in the control group (WMD: -1.699, 95%CI:-2.428--0.970, P<0.001). PFMT showed a better effect for UI than the routine nursing.

Lu, Y., et al. (2023). "Application of robotic surgery and traditional laparoscopic surgery in lymph node dissection for gynecological cancer: A meta‑analysis." Oncology Letters 25(5): 175.
	Since the advantages of robotic surgery and laparoscopic surgery in the number of lymph node resections are not well understood, this meta-analysis used evidence-based medicine to assess the difference in the number of lymph nodes retrieved in gynecological cancer between the two surgical methods to guide clinical treatment. In the present meta-analysis, the Pubmed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang libraries were searched for articles that were published from the time of the database's inception to January 2021, including cohort studies and randomized controlled trials, where the observation group underwent robotic surgery to treat gynecological cancers and the control group underwent laparoscopic surgery to treat gynecological cancers, including cervical and ovarian cancers and endometrial cancers. Duplicate publications, studies with no full text, incomplete information or where the authors were unable to perform data extraction, animal experiments, reviews and systematic reviews were excluded. STATA 15.1 was used to analyze the data. Robotic surgery resulted in a significant increase in the number of lymph nodes retrieved from the pelvis [standard mean difference (SMD)=0.24; 95% CI, 0.04-0.45; P=0.007] and para-aortic (SMD=0.41; 95% CI, 0.13-0.69; P=0.004) regions compared with the number retrieved by laparoscopic surgery. Furthermore, there was no significant difference in operating time between robotic and laparoscopic surgery, despite the use of different instruments (SMD=0.12; 95% CI, -0.35-0.58; P=0.616). The amount of blood lost during robotic surgery was significantly less compared with that lost during laparoscopic surgery [SMD=-0.40; 95% CI, -0.58-(-0.22); P<0.001]. The present study evaluated cancer recurrence and death in further detail, and no statistically significant difference was demonstrated between robotic surgery and laparoscopic surgery in terms of recurrence rate [odds ratio (OR)=0.59; 95% CI, 0.21-1.65; P=0.318] and mortality rate (OR=0.31; 95% CI, 0.08-1.30; P=0.109). The present study demonstrated that robotic surgery was able to retrieve more pelvic and para-aortic lymph nodes than traditional laparoscopic surgery, which was consistent with previous reports. With regards to blood loss, The difference in operation time between the two surgical methods was not statistically significant, whereas the estimated blood loss of robotic surgery was significantly lower than that of traditional laparoscopic surgery. There was no statistically significant difference in the recurrence rate and mortality rate of the two surgical modality.; Competing Interests: The authors declare that they have no competing interests. (Copyright: © Lu et al.)

Lu, Z.-H. and X.-Q. Kang (2019). "Effectiveness of advanced nursing care on depression in patients with ovarian cancer: A protocol of systematic review of randomized controlled trial." Medicine 98(17): e15316.
	Background: This systematic review will assess the effectiveness of advanced nursing care (ANC) on depression in patients with ovarian cancer (OC).; Methods: We will identify any relevant randomized controlled trial from Cochrane Library, MEDLINE, Embase, Web of Science, Springer, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their inceptions to March 5, 2019. The primary outcome includes depression. The secondary outcomes consist of anxiety, quality of life, and adverse events. Data that meets all the eligibility criteria will be extracted, pooled, and analyzed by using RevMan 5.3 software. Methodological quality for each eligible study will be assessed by using Cochrane risk of bias tool.; Results: This study will analyze depression, anxiety, quality of life, and adverse events of ANC on depression in patients with OC.; Conclusion: The findings of this study will provide the latest evidence for the effectiveness and adverse events of ANC on depression in patients with OC.; Ethics and Dissemination: No ethic approval is required for this study, because all the data will be extracted from previous published studies. The results of this study will be presented at conference or will be published at a peer-reviewed journal.; Prospero Registration Number: PROSPERO CRD42019126374.

Luan, L., et al. (2021). "Comparison of the two routes of video endoscopic inguinal lymphadenectomy in vulvar cancer: a systematic review and a single-center experience." Translational cancer research 10(2): 1034-1042.
	Background: Video endoscopic inguinal lymphadenectomy (VEIL) has fewer complications than open surgery for vulva cancer. No high-level evidence comparing the efficacy and safety of the two routes of VEIL (VEIL-H and VEIL-L) is available.; Methods: We performed a comprehensive literature search for reports on VEIL for vulva cancer from 2000 to 2020 and reviewed our experience. Data extraction includes patients' characteristics, perioperative indicators, postoperative complications, and cancer recurrence.; Results: A total of 11 eligible studies were included in the systematic review. Nine studies included only one route of VEIL, and the other two studies directly compared the two routes of VEIL. The average operation time of the VEIL-L group was 85 (range, 33-180.12) minutes, and that of the VEIL-H group was 112 (range, 35-170.79) minutes. The average blood loss of the VEIL-L group was 9 (range, 5-30) mL, and that of the VEIL-H group was 96 (range, 5.5-214.8) mL. The average number of intraoperatively removed lymph nodes in the VEIL-L group was 9 (range, 7.5-13.2), and that in the VEIL-H group was 14 (range, 9.5-16). No significant difference was observed in the cancer recurrence rate between the two groups. We found similar results in our cohort study.; Conclusions: The operation time, intraoperative blood loss, and time of drainage of the VEIL-L procedure seemed less than those of the VEIL-H procedure. VEIL-L and VEIL-H were equivalent in the efficacy of lymph node dissection, surgery-related complications, and cancer recurrence rate.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-2690). The authors have no conflicts of interest to declare. (2021 Translational Cancer Research. All rights reserved.)

Luchristt, D., et al. (2021). "Cost-effectiveness Analysis of Universal Cystoscopy at the Time of Benign Laparoscopic Hysterectomy." Journal of Minimally Invasive Gynecology 28(8): 1470-1483.
	Study Objective: To estimate the rate of lower urinary tract injury (LUTI) and percentage of LUTI needing to be recognized intraoperatively to make universal cystoscopy cost-effective and cost-saving during laparoscopic hysterectomy. Design(s): A decision tree model was used to estimate the costs and quality-adjusted life years associated with delayed or intraoperative recognition of LUTI at the time of laparoscopic hysterectomy. Probabilities and utilities were estimated from published literature. Costs were estimated from Medicare national reimbursement schedules. Threshold analyses estimated the LUTI rate and cystoscopy sensitivity that would make universal cystoscopy cost-effective or cost-saving. Monte Carlo simulations were performed. Setting(s): US healthcare system. Patient(s): Individuals undergoing laparoscopic hysterectomy for benign indications. Intervention(s): Theoretic implementation of a universal cystoscopy policy. Measurements and Main Results: The total direct medical costs of laparoscopic hysterectomy under usual care were $8831 to $9149 and under universal cystoscopy were $8944 to $9068. When low LUTI rates (0.44%; estimated using sample-weighted estimates of retrospective and prospective data) were assumed, universal cystoscopy was only cost-effective in 17.1% of the simulations; the incremental cost was estimated to be $111 to $131. With median LUTI rates (2.3%) or high LUTI rates (4.0%; estimated using only prospective data with universal screening), the universal cystoscopy strategy was cost-effective in 93.9% and 99.6% of the simulations, respectively, and potentially cost-saving if the sensitivity of intraoperative cystoscopy for ureteral injury exceeded 65% or 31%, respectively. The estimated potential savings were $18 to $95 per hysterectomy. In threshold analysis assuming the average cystoscopy sensitivity rate, universal cystoscopy is estimated to be cost-effective when the LUTI rate exceeds 0.80%. Conclusion(s): In our model, universal cystoscopy is the preferred approach for laparoscopic hysterectomy and is estimated to be cost-effective in contemporary clinical settings where the LUTI rate is estimated to be 1.8% and potentially cost-saving among higher-risk populations, including those with endometriosis or pelvic organ prolapse. If the LUTI rates are less than 0.75%, the estimated incremental costs are modest-up to $131 per case. Administrators and providers should consider the local LUTI rates and practice patterns when planning implementation of a universal cystoscopy policy.Copyright © 2020 AAGL

Lucine and Biotrial (2021). Endocare for Pelvic-perineal Pain Related to Endometriosis Used at Home.
	No Results Available Device: Endocare|Device: Digital control Pain intensity change|Change in pain intensity|Change in pain relief|Weighted average change in pain intensity|Change in stress value|Change in fatigue value|Change in endometriosis-related quality of life|Assessment of the predictive value of dramatization and catastrophizing thoughts|Pain relief treatments|Assessment of satisfaction|Assessment of Clinical Global Impression of Improvement|Incidence of adverse events and treatment adherence Female Not Applicable 120 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 2021-A02358-33 September 2022

Ludwig, P., et al. (2020). "Pregnancy success and outcomes after uterine fibroid embolization: updated review of published literature." The British journal of radiology 93(1105): 20190551.
	Females with symptomatic leiomyomas (fibroids) wishing to maintain fertility are faced with difficult treatment choices. These include uterine fibroid embolization (UFE), myomectomy, hormonal therapy, MRI high intensity focused ultrasound, and myolysis. This review focuses on UFE, one of the most commonly accepted minimally invasive procedural choices among patients with symptomatic fibroids wishing to retain the option of becoming pregnant in the future, and makes comparisons to myomectomy which has historically been the surgical choice for fertility-preserving fibroid treatment. Pubmed and Google Scholar searches using keywords such as: uterine artery embolization, uterine fibroid embolization, pregnancy, complications, infertility were performed between Jan. 1, 2019 and May 10, 2019. Publications were chosen based on their inclusion of information pertaining to fertility or pregnancy after UFE without being limited to single case reports.Randomized controlled trials comparing myomectomy and UFE are limited due to study size and confounding variables, but through registry data and familiarity with referring clinicians, UFE has gained wide acceptance. Healthy pregnancies following UFE have been sporadically reported but the actual fertility rate after UFE remains uncertain. Conversely, low birth weight, miscarriage and prematurity have been associated with UFE. Despite inherent risks of possible fertility issues after UFE, the procedure remains an option for females with clinically symptomatic fibroids who desire pregnancy. However, additional research regarding rates of conception and obstetrical risks of infertility following UFE is necessary.

Luebeck University, o. (2022). Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation.
	No Results Available Biological: autologous PRP (platelet rich plasma)|Other: Saline solution (NaCL) Injection Ovarian response|Hormone levels|Follicular response|COCs and MII oocytes|Number of 2PN oocytes|Mean number and quality of embryos|Biochemical pregnancy rate|Clinical pregnancy rate|Ongoing pregnancy rate|Miscarriage rate|Still birth rate|Live birth rate|Gestational age|Weight of newborn|Length of newborn|Incidence of birth sex|Incidence of multiple birth|Neonatal health|Post procedure pain|Fertility Quality of Life Questionnaire|Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Female Not Applicable 140 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment Aktenzeichen 21-348 March 17, 2027

Luginbuehl, H., et al. (2022). "Intervention effects maintenance: 6-month randomized controlled trial follow-up of standard and reflexive pelvic floor muscle training." AJOG Global Reports 2(4): 100089.
	BACKGROUND: To date, the focus of pelvic floor muscle training for women suffering from stress urinary incontinence has been on voluntary contractions although involuntary pelvic floor muscle contractions are crucial to guarantee continence in high-impact situations typically triggering this condition. The authors developed 2 pelvic floor muscle home training programs, one including standard voluntary pelvic floor muscle training and one including involuntary reflexive pelvic floor muscle training. OBJECTIVE(S): This study aimed to test 2 pelvic floor muscle home training programs regarding maintenance of effects of a previous 16-week intervention in terms of stress urinary incontinence symptoms (International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence short form, modified 20-minute pad test), impact on quality of life (Lower Urinary Tract Symptoms Quality of Life module), and digitally assessed pelvic floor muscle strength. STUDY DESIGN: This trial was a continuation of a previously published triple-blind prospective randomized controlled trial with a 6-month evaluation endpoint with 2 intervention groups (experimental group with involuntary reflexive home pelvic floor muscle training and control group with standard voluntary home pelvic floor muscle training). RESULT(S): From the originally included 96 randomized and allocated participants (experimental group=46, control group=46), 33 control and 27 experimental participants completed the 6-month follow-up. From post-16-week physiotherapy intervention to 6-month follow-up (home pelvic floor muscle training), there were statistically significant improvements in pelvic floor muscle strength (control and experimental group), and no difference in the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence short form and pad test, or the Lower Urinary Tract Symptoms Quality of Life module Part B (control and experimental group) and Part A (control group). However, there was a statistically significant improvement in the Lower Urinary Tract Symptoms Quality of Life module Part A (experimental group). At no point in time (pre, post, follow-up) was there any statistically significant difference between the groups. CONCLUSION(S): Both groups could maintain their intervention training effects. This trial investigated involuntary reflexive pelvic floor muscle training alone, which proved to be an effective alternative to standard voluntary pelvic floor muscle training for maintenance of training effects among women suffering from stress urinary incontinence.Copyright © 2022 The Authors

Lulu, F., et al. (2022). "A systematic review and meta analysis evaluating the role of granulocyte colony-stimulating factor for IVF group with thin endometrium, recurrent implantation failure, recurrent spontaneous abortion or not." PROSPERO International prospective register of systematic reviews.
	
Lumsden, M., et al. (2021). "Uterine artery embolization or myomectomy for fibroids: The FEMME randomised controlled trial." BJOG: An International Journal of Obstetrics and Gynaecology 128(SUPPL 2): 9-10.
	Objective To examine the clinical and cost-effectiveness of uterine artery embolization compared to myomectomy in the treatment of symptomatic uterine fibroids. Design A multicentre, open, randomised trial, with parallel economic evaluation. Method Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolization were recruited. Women were excluded if they had significant adenomyosis, any malignancy, pelvic inflammatory disease or had had a previous open myomectomy or uterine artery embolization. Participants were randomised to myomectomy or embolization in a 1:1 ratio using a minimization algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic. Embolization of the uterine arteries was performed under fluoroscopic guidance. The primary outcome was quality of life, using the Uterine Fibroid Symptom Quality of Life questionnaire (UFS-QOL, range 0-100 [higher indicating better quality of life]) at two years, adjusting for baseline score. The economic evaluation used quality-adjusted life years (QALYs) derived from EQ-5D-3L and costs from a NHS and personal social services perspective. Results 254 women were randomized, 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolization (98 underwent embolization). Information on the primary outcome at two years was available in 81% (206 women). Primary outcome scores at 2 years were 84.6 (standard deviation [SD] 21.5) in the myomectomy group, versus 80.0 (SD 22.0) in the uterine artery embolization group (intention to treat complete case analysis mean adjusted-difference 8.0; 95% confidence interval [CI] 1.8-14.1; P = 0.01). The mean difference in the primary outcome at the four-year follow-up timepoint was 5.0 points (95%CI -1.4 to 11.5; P = 0.13) in favour of myomectomy. Peri-and post-operative complications from all initial procedures occurred in similar percentages of women in both groups (29% versus 24%, respectively). Twelve women in the uterine embolization group and 6 in the myomectomy group reported pregnancies over 4 years, resulting in 7 and 5 live births, respectively (hazard ratio: 0.48, 95%CI 0.18-1.28). Over two years, uterine artery embolization was associated with higher costs than myomectomy: mean costs 7665 (95%CI 6068-9262) and 7208 (95%CI 5714-8703) respectively, but lower QALYs gained (difference -0.06, 95% -0.11to -0.02). Similar results were observed over the 4-year horizon. Conclusion Among women with symptomatic uterine fibroids, myomectomy resulted in better fibroid-related quality of life at 2 years, compared with uterine artery embolization. The differences in costs and QALYs are very small. Future research should involve women who are desiring pregnancy.

Luo, F., et al. (2019). "Comparative efficacy and safety of NSAIDs-controlled acupuncture in the treatment of patients with primary dysmenorrhoea: a Bayesian network meta-analysis." The Journal of International Medical Research 47(1): 19-30.
	Background: Acupuncture and non-steroidal anti-inflammatory drugs (NSAIDs) are used frequently to treat primary dysmenorrhoea. However, it is unclear whether this treatment greatly reduces the risk of primary dysmenorrhoea.; Methods: Eight databases were searched up to January 2018. Pair-wise and network meta-analyses were conducted to synthesize data from eligible studies.; Results: Seventeen randomized controlled trials were included. The following acupuncture types showed more efficacy than NSAIDs in reducing primary dysmenorrhoea risk: traditional acupuncture (odds ratio [OR] = 6.70, 95% confidence interval [CI] 2.60-20.0), eye acupuncture (OR = 3.50, 95% CI 1.40-8.90), wrist-ankle acupuncture (OR = 6.00, 95% CI 1.30-32.0), superficial acupuncture (OR= 5.10, 95% CI 1.20-26.0), moxibustion (OR = 7.70, 95% CI 2.90-25.0), electroacupuncture (OR = 23.0, 95% CI 4.80-130), ear acupuncture (OR = 13.0, 95% CI 2.80-100) and abdominal acupuncture (OR = 5.30, 95% CI 2.10-16.0). Surface under the cumulative ranking curve values were traditional acupuncture (53.0%), eye acupuncture (22.0%), wrist-ankle acupuncture (81.5%), superficial acupuncture (50.0%), moxibustion (57.8%), electroacupuncture (99.9%), ear acupuncture (41.6%) and abdominal acupuncture (44.1%).; Conclusion: Acupuncture is more efficacious than NSAIDs in reducing primary dysmenorrhoea risk. Acupuncture, particularly electroacupuncture, can decrease the risk of primary dysmenorrhoea.

Luo, J., et al. (2019). "The effect of salpingectomy on the ovarian reserve and ovarian response in ectopic pregnancy: A systematic review and meta-analysis." Medicine (United States) 98(47): e17901.
	Background:Salpingectomy is routinely performed in ectopic pregnancy (EP). However, the effect of the surgery on the ovarian reserve and ovarian response in EP patients is still uncertain and has not been systematically evaluated. Therefore, we conducted this meta-analysis to provide a comparison of the ovarian reserve and ovarian response between the pre-salpingectomy and post-salpingectomy in EP patients. Method(s):Pubmed, Embase, and Cochrane Library were searched for all relevant articles published up to December 2018. We retrieved the basic information and data of the included studies. The data was analyzed by Review Manager 5.3 software (Cochrane Collaboration, Oxford, UK). Result(s):A total of 243 articles were extracted from the databases, and 7 studies were included in the meta-analysis. The ovarian reserve including anti-Mullerian hormone (inverse variance [IV] -0.7 [95% confidence interval [CI] -0.63, 0.49]), antral follicle count (IV 1.7 [95% CI -2.02, 5.42]) and basal follicle stimulating hormone (IV 0.02 [95% CI -0.63, 0.68]) was comparable between the pre-salpingectomy group and the post-salpingectomy group. The amount of gonadotropin was significantly higher in the post-salpingectomy group when compared with that in the pre-salpingectomy group (IV -212.65 [95% CI -383.59, -41.71]). There was no significant difference in the left parameters of the ovarian response including the duration of gonadotropin stimulation (IV -0.32 [95% CI -0.76, 0.12]), the estrogen level on the human chorionic gonadotropin triggering day (IV -4.12 [95% CI -236.27, -228.04]) and the number of retrieved oocytes (IV 0.35 [95% CI -0.76, 1.46]) between 2 groups. Conclusion(s):The current results suggest that salpingectomy has no negative effect on the ovarian reserve and ovarian response.Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

Luo, N., et al. (2022). "The effect of acupuncture on condition being studied emotional disorders in patients with postpartum: A protocol for systematic review and meta-analysis." Medicine 101(4): e28669.
	Background: As one of the common postpartum diseases, postpartum emotional disorders (PEDs) mainly include postpartum depression, postpartum anxiety, posttraumatic stress disorder, and obsessive-compulsive disorder, which significantly affect the patient's quality of life. Acupuncture has been widely used as a popular alternative complementary therapy for the treatment of PEDs. Nevertheless, its effectiveness and safety remain uncertain. Hence, the first systematic review and meta-analysis will be urgently executed to explore the effectiveness and safety of acupuncture in the treatment of PEDs.; Methods: Eight databases will be searched, including the PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, and Technology Periodical Database. Only randomized controlled trials of acupuncture for PEDs will be considered. The languages are limited to English and Chinese. All publications were retrieved by 2 researchers independently. Assessment of the Edinburgh Postpartum Depression Scale will be dedicated as a primary outcome, and secondary outcomes include the Hamilton Anxiety Inventory, the Hamilton Depression Inventory, the Orientation to Life Questionnaire (sense of coherence 29-item scale), and adverse effects of acupuncture. The Cochrane Risk of Bias tool will be used to assess the quality of the eligible publications. Additionally, the level of evidence for results will be evaluated by using the Grades of Recommendation, Assessment, Development, and Evaluation method. All data will be analyzed statistically by using RevMan V.5.3 software.; Results: This study will provide a high level of the evidence-based basis for the effectiveness and safety of acupuncture in the treatment of PEDs.; Conclusion: The findings of this study will assess the safety, efficacy, and adverse effects of acupuncture in the treatment of PEDs.; Ethics and Dissemination: No ethical approval is required as patient data will not be collected. In addition, the results of this meta-analysis will be disseminated through publication in peer-reviewed scholarly journals or relevant academic conferences.; Registration Number: INPLASY 2021120091.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Luo, P., et al. (2023). "Effects of Sleeve Gastrectomy on Patients with Obesity and Polycystic Ovary Syndrome: a Meta-analysis." Obesity surgery 33(8): 2335-2341.
	Purpose: This study aimed to evaluate the efficacy of sleeve gastrectomy (SG) on patients with obesity and polycystic ovary syndrome (PCOS).; Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies published prior to December 2, 2022. Meta-analysis was performed on menstrual irregularity, total testosterone, sex hormone-binding globulin (SHBG), anti-Mullerian hormone (AMH), glucolipid metabolism indicators, and body mass index (BMI) following SG.; Results: Six studies and 218 patients were included in the meta-analysis. Following SG, menstrual irregularity significantly decreased (odds ratio [OR] 0.03; 95% confidence intervals [CIs], 0.00-0.24; P=0.001). Additionally, SG can lower total testosterone levels (MD -0.73; 95% CIs -0.86-0.60; P< 0.0001), as well as BMI (MD -11.59; 95% CIs -13.10-10.08; P<0.0001). A significant increase was observed in the levels of SHBG and high-density lipoprotein (HDL) after SG. In addition to reducing fasting blood glucose, insulin, triglycerides (TG), and low-density lipoprotein levels, SG significantly reduced low-density lipoprotein levels as well.; Conclusions: Following SG, we firstly demonstrated significant improvements in menstrual irregularity, testosterone and SHGB levels, glycolipid metabolism indicators, and BMI. Therefore, SG may be considered as a new option for the clinical treatment of patients with obesity and PCOS. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Luo, Y., et al. (2020). "Auricular acupuncture for premature ovarian insufficiency: A protocol for systematic review and meta-analysis." Medicine 99(39): e22212.
	Background: A lot of attention has been given to premature ovarian insufficiency (POI) as it poses considerable health risks to women. It is characterized by oligomenorrhea, amenorrhea, infertility, autoimmune disorders, and ischemic heart disease, with increased mortality. Previous research indicates that auricular acupuncture is proven effective in treating POI in clinical practice. However, systematic review has not been carried out. Therefore, this study aims at evaluating the curative effect and safety of auricular acupuncture treatment for POI through systematic review and meta-analysis.; Methods and Analysis: The following databases will be searched for relevant information before August 2020: PubMed, Embase, Cochrane Library, Web of Science, and CNKI.; Major Results: levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2). Secondary results: modified Kupperman Index, imaging results including ovarian size, antral follicle count, and blood flow changes in the ovary using color Doppler ultrasound; total effective rate, adverse event and intervention, and hospitalization expenses. Data will be collected independently by 2 researchers, and the risk of bias in meta-analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions". All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0.; Results: The curative effect and safety of auricular acupuncture treatment for POI patients will be evaluated systematically.; Conclusion: In the systematic review, the published evidence of auricular acupuncture treatment for POI will be summarized to provide guidance for promotion and application.; Ethics and Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.Open Science Framework (OSF) registration number: http://osf.io/tg9mw.

Luque, G., et al. (2023). "Fezolinetant: A new treatment being studied for menopause." Clinica e Investigacion en Ginecologia y Obstetricia 50(4): 100888.
	Menopause is the physiological cessation of menstruation that can occur in women between 42 and 58 years of age with diverse symptoms. The most common clinic is vasomotor, which can greatly affect the quality of life of women. Traditionally, hormone replacement therapy has been used and is considered the most effective treatment. However, there are contraindications for which the use of non-hormonal therapy should be considered. Nowadays, these options are suboptimal in terms of effectiveness and tolerance, which is why research is being carried out on new treatments such as fezolinetant, a neurokinin 3 receptor antagonist. To elucidate these investigations a bibliographic search has been carried out in the main databases. Although its safety and long-term effects remain to be established, fezolinetant looks promising in patients for whom hormonal therapy cannot be used. It decreases statistically significant the moderate or severe vasomotor symptoms from the first day of treatment when compared with placebo and with other non-hormonal treatments with a good tolerance profile and few side effects. However, this drug is still in phase III trials, so it needs to continue with its study.Copyright © 2023 Elsevier Espana, S.L.U.

Lurain, K., et al. (2020). "Anti-PD-1 and Anti-PD-L1 Monoclonal Antibodies in People Living with HIV and Cancer." Current HIV/AIDS Reports 17(5): 547-556.
	Purpose of Review: Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) pathway are a class of anti-cancer immunotherapy agents changing treatment paradigms of many cancers that occur at higher rates in people living with HIV (PLWH) than in the general population. However, PLWH have been excluded from most of the initial clinical trials with these agents. Recent Findings: Two recent prospective studies of anti-PD-1 agents, along with observational studies and a meta-analysis, have demonstrated acceptable safety in PLWH. Preliminary evidence indicates activity in a range of tumors and across CD4+ T cell counts. Summary: Safety and preliminary activity data suggest monoclonal antibodies targeting PD-1 or its ligand, PD-L1, are generally appropriate for PLWH and cancers for which there are FDA-approved indications. Ongoing and future trials of anti-PD-1 and anti-PD-L1 therapy alone or in combination for HIV-associated cancers may further improve outcomes for this underserved population.Copyright © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Luvian-Morales, J., et al. (2023). "The effect of an anti-inflammatory diet on cervical cancer patients." Clinical Nutrition ESPEN 58: 504.
	Rationale: Gastrointestinal (GI) toxicity and malnutrition are common illnesses in patients with locally advanced cervical cancer (LACC) treated with chemoradiation therapy (CRT). Both could be, in part, the result of inflammation caused by pelvic radiation (Najafi M, et al, 2018). A low residue diet (LRD) is routinely used for patients that receive CRT (Bye A, et al, 1992); however, several foods have been demonstrated to have the capability to modulate inflammation in chronic diseases (Luvian-Morales J, et al, 2022). In this study was evaluated the effect of an anti-inflammatory diet (AID) on nutritional status, GI toxicity symptoms, and inflammation compared with LRD in patients receiving CRT. Method(s): This study is an open, controlled, randomized clinical trial performed on women with LACC. Dietary requirements were calculated according to previous reports (Medina-Contreras O, et al, 2020; Castro-Eguiluz D, et al, 2018). Nutritional status, GI toxicity, and inflammation were evaluated. Five visits were carried out. Result(s): Thirty-three patients were included in this analysis per protocol, 19 and 14 in AID and LRD, respectively. There were no differences in energy or macronutrient intake between the groups; however, the AID group consumed higher quantities of fiber, lactose, -3 fatty acids, probiotics, and antioxidants than the LRD group. There were no differences in malnutrition or GI toxicity. A preliminary analysis showed the AID group trended to decrease calprotectin in feces and C reactive protein in serum. Those patients without adherence to diets presented more malnourished patients at the end of this study (0 vs. 0 vs. 19.2%, p=0.001). Conclusion(s): We found no evidence of any benefit of LRD, limiting fiber, lactose, and fat, in patients with LACC under CRT. On the contrary, an AID diet could reduce inflammation secondary to oncological treatment. It is necessary to improve adherence to diets to prevent malnutrition. Disclosure of Interest: None declaredCopyright © 2023

Lv, T. and Z. Minru (2022). "Clinical Effectiveness of Physical Therapy for People with Chronic Prostatitis/Chronic Pelvic Pain&#xff1a; A Systematic Review and Meta-Analysis."
	
Lv, X., et al. (2020). "Efficacy and safety of neoadjuvant chemotherapy versus primary debulking surgery in patients with ovarian cancer: a meta-analysis." Journal of Gynecologic Oncology 31(2): e12.
	Objective: Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC.; Methods: PubMed, Embase, ClinicalTrials.gov, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords "ovarian cancer/neoplasms", "primary debulking surgery", and "neoadjuvant chemotherapy".; Results: The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13-1.49; heterogeneity: p<0.001, I²=82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32-2.17; heterogeneity: p<0.001, I²=81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06-0.51; heterogeneity: p=0.698, I²=0%) and major infection (RR=0.29, 95% CI=0.17-0.51; heterogeneity: p=0.777, I²=0%) compared with patients administered PDS.; Conclusions: This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients.; Trial Registration: PROSPERO Identifier: CRD42019120625.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Lv, Z., et al. (2023). "A meta-analysis of treatment for early-stage cervical cancer: open versus minimally invasive radical trachelectomy." BMC Pregnancy and Childbirth 23(1): 727.
	Background: In previous systematic reviews, meta-analysis was lacking, resulting in the statistical difference between the data of different surgeries being impossible to judge. This meta-analysis aims to contrast the fertility results and cancer outcomes between open and minimally invasive surgery.; Method: We systematically searched databases including PubMed, Embase, Cochrane, and Scopus to collect studies that included open and minimally invasive radical trachelectomy. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4.; Result: Eight studies (1369 patients) were incorporated into our study. For fertility results, the Open group excels MIS group in pregnancies-Third trimester delivery [OR = 2.68; 95% CI (1.29, 5.59); P = 0.008]. Nevertheless, there is no statistical difference in clinical pregnancy, miscarriage, and second-trimester rate. Concerning cancer outcomes, no difference was detected in the overall survival [OR = 1.56; 95% CI (0.70, 3.45); P = 0.27] and recurrence [OR = 0.63; 95% CI (0.35, 1.12); P = 0.12]. Concerning surgery-related outcomes, the comprehensive effects revealed that the estimated blood loss of the Open group was higher than that of the MIS group[MD = 139.40; 95% CI (79.05, 199.75); P < 0.0001]. However, there was no difference between the postoperative complication rate in the two groups [OR = 1.52; 95% CI (0.89, 2.60); P = 0.12].; Conclusion: This meta-analysis suggested that the fertility result of the Open group may be better than the MIS group, while the MIS group has better surgery-related outcomes. Owing to the poor cases of our study, a more robust conclusion requires more relevant articles in the future.; Systematic Review Registration: PROSPERO CRD42022352999. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Lysdal, V. K., et al. (2022). "Lateral coagulation of the uterine artery at its origin prior to total laparoscopic hysterectomy. A randomized control trial." Journal of Gynecology Obstetrics and Human Reproduction 51(9): 102465.
	Background and Objectives: Lateral occlusion prior to TLH has been suggested to reduce perioperative bleeding, operative time, and hospital stay. Furthermore, reducing the amount of bleeding and the length of the operation may affect parameters such as postoperative pain and the number of patients with postoperative vaginal vault hematoma. Method(s): This RCT was conducted at a single center at Odense University Hospital in Denmark. Between February 2016 and February 2019, a total of 58 patients undergoing TLH and bilateral salpingectomy for benign cases were recruited to the study. Result(s): The mean operating time was significantly longer in the LA group with a mean difference between the two groups of six minutes. No other discrepancy regarding the primary outcomes was observed between the two groups. Total blood loss was similar in the two groups as well as the average hospital stay and the VAS score during the first seven days. 93% of the patients were discharged from the hospital within the first 24 h postoperatively. Conclusion(s): This RCT demonstrates that lateral occlusion of the uterine artery prior to TLH does not improve outcome for the patients and should therefore not be used as a standard procedure.Copyright © 2022 Elsevier Masson SAS

Lysdal, V. K., et al. (2022). "Lateral closure of the uterine artery prior to laparoscopic hysterectomy: a systematic review." Journal of Obstetrics and Gynaecology 42(5): 785-792.
	An alternative surgical technique with closure of the uterine artery at its origin, known as lateral approach prior to TLH, has been proposed and it may offer important benefits to both patients and surgeons. Our objectives were to review the current literature regarding surgical outcomes between lateral and conventional approach in relation to TLH. We followed the 'PRISMA' guidelines and conducted a systematic review, which involved searching PubMed and Embase databases for RCTs evaluating the topic. We identified four RCTs including 585 patients. Three of the four studies reported a significant lower bleeding during TLH with prior lateral approach. Operative time was also shorter in the lateral approach group compared to the conventional approach group in three studies. Our review provides evidence that lateral occlusion of the uterine arteries prior to total laparoscopic hysterectomy may be beneficial due to less blood loss and shorter perioperative time without compromising patient safety.Copyright © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Ma, C., et al. (2021). "Danggui Sini Decoction (herbal medicine) for the treatment of primary dysmenorrhoea: a systematic review and meta-analysis." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 41(7): 1001-1009.
	Danggui Sini Decoction (DSD), a traditional herbal prescription, has been commonly used in the treatment of primary dysmenorrhoea (PD). We investigated the current evidence of randomised controlled trials (RCTs) and performed a systematic review to evaluate the efficacy of DSD in the treatment of PD. We registered the protocol for this systemic review in PROSPERO with the registration number CRD 42017074062 on August 10, 2017. Nine databases were searched from inception to August 2019. Eleven RCTs with 1005 patients were included. DSD was shown to have more favourable effects on the clinical effective rate than western medicine, which support the clinical use of DSD in the treatment of PD. However, considering the high risk of bias in the included studies, more well-designed RCTs are needed to further evaluate the efficacy of DSD in the treatment of PD.

Ma, F., et al. (2020). "Effects of herb-partitioned moxibustion for primary dysmenorrhea: A protocol for systematic review and meta-analysis." Medicine 99(29): e21253.
	Background: Primary dysmenorrhea (PD) is a cyclic cramp in pelvic which affects the quality of life. Herb-partitioned moxibustion (HPM), a critical component of moxibustion therapy in traditional Chinese medicine, has been used to treat PD. However, there is still a lack of high-quality evidence to support the effectiveness and safety of HPM on patients with PD. The object of this work is to evaluate the efficacy and safety of HPM in the management of PD.; Methods: The Embase, MEDLINE, PubMed, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database, Wan fang database, Chongqing VIP information, and SinoMed will be searched from their inception to Jun 2020. All randomized controlled trials of HPM for the treatment of PD will be included. We will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by RevMan 5.3 (The Cochrane Collaboration, Oxford, England).; Results: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of HPM for the treatment of PD.; Conclusion: The conclusion of our systematic review will give more convincing evidence to assist clinicians during the decision-making process when dealing with PD.; Trial Registration Number: 10.17605/OSF.IO/UFKNP.

Ma, J., et al. (2023). "The effectiveness and safety assessment of robotic assisted myomectomy: systematic review and meta analysis."
	
Ma, J., et al. (2022). "Prognosis and Efficacy of Laparoscopic Surgery on Patients with Endometrial Carcinoma: Systematic Evaluation and Meta-Analysis." Computational and mathematical methods in medicine 2022: 9384134.
	Objective: The prognosis and efficacy of laparoscopic surgery (LPS) and open surgery or robotic surgery (RS) on endometrial carcinoma (EC) patients were compared.; Methods: Data as of May 2021 were retrieved from databases like PubMed, Embase, Cochrane Library, and Web of Science. The study involved randomized controlled trials (RCTs), cohort studies, or case-control studies for comparing the effects of LPS and open surgery or robotic surgery (RS) on EC treatment. The primary outcomes included duration of operation, blood loss, length of stay (LOS), postoperative complications, and recurrence rate. Secondary outcomes included 3-year progression-free survival (PFS) rate/disease-free survival (DFS) rate and 3-year overall survival (OS) rate.; Results: A total of 24 studies were involved, and all of them were cohort studies except 1 RCT and 1 case-control study. There was no significant difference in duration of operation between LPS and open surgery (MD = -0.06, 95% CI: -0.37 to 0.25) or RS (MD = -0.15, 95% CI: -1.27 to 0.96). In comparison with the open surgery, LPS remarkably reduced blood loss (MD = -0.43, 95% CI: -0.58 to -0.29), LOS (MD = -0.71, 95% CI: -0.92 to -0.50), and the complication occurrence rate (RR = 0.83, 95% CI: 0.73 to 0.95). However, LPS and RS saw no difference in blood loss (MD = 0.01, 95% CI: -0.77 to 0.79). Besides, in comparison with RS, LPS prominently shortened the LOS (MD = 0.26, 95% CI: 0.12 to 0.40) but increased the complication occurrence rate (RR = 1.74, 95% CI: 1.57 to 1.92). In contrast to open surgery or RS, LPS saw no difference in occurrence rate (RR = 0.75, 95% CI: 0.56 to 1.01; RR = 0.97, 95% CI: 0.62 to 1.53), 3-year PFS/DFS (RR = 0.99, 95% CI: 0.90 to 1.09; RR = 1.30, 95% CI: 0.87 to 1.96), and 3-year OS (RR = 0.97, 95% CI: 0.91 to 1.04; RR = 1.21, 95% CI: 0.91 to 1.60).; Conclusion: In sum, LPS was better than open surgery, which manifested in the aspects of less blood loss, shorter LOS, and fewer complications. LPS, therefore, was the most suitable option for EC patients. Nevertheless, LPS had no advantage over RS, and sufficient prospective RCTs are needed to further confirm its strengths.; Competing Interests: The authors declare no conflicts of interest. (Copyright © 2022 Jiong Ma et al.)

Ma, L., et al. (2021). "Laparoscopic nerve‑sparing radical hysterectomy for the treatment of cervical cancer: a meta-analysis of randomized controlled trials." World Journal of Surgical Oncology 19(1): 301.
	Background: The effects and safety of laparoscopic nerve‑sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) in cervical cancer treatment remain unclear. This article aims to evaluate the role of LNSRH versus LRH in the treatment of cervical cancer. This is because the updated meta-analysis with synthesized data may provide more reliable evidence on the role of LNSRH and LRH.; Methods: We searched Pubmed et al. databases for randomized controlled trials (RCTs) involving laparoscopic nerve‑sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH) for cervical cancer treatment from the inception of databases to June 15, 2021. The RevMan 5.3 software was used for data analyses. This meta-analysis protocol had been registered online (available at: https://inplasy.com/inplasy-2021-9-0047/ ).; Results: Thirteen RCTs involving a total of 1002 cervical cancer patients were included. Synthesized results indicated that the duration of surgery of the LNSRH group was significantly longer than that of the LRH group [SMD 1.11, 95% CI (0.15 ~ 2.07), P = 0.02]. The time to intestinal function recovery [SMD -1.27, 95% CI (-1.84 ~ -0.69), P < 0.001] and the time to postoperative urinary catheter removal of the LNSRH group [SMD -1.24, 95% CI (-1.62 ~ -0.86), P < 0.001] were significantly less than that of the LRH group. There were no significant differences in the estimated blood loss [SMD 0.10, 95% CI (-0.14 ~ 0.34), P = 0.41], the length of parauterine tissue resection [SMD -0.10, 95% CI (-0.25 ~ 0.05), P = 0.19], length of vaginal excision [SMD 0.04, 95% CI (-0.26 ~ 0.34), P = 0.78], and incidence of intraoperative adverse events [RR 0.97, 95% CI (0.44 ~ 2.13), P = 0.94] between the LNSRH group and the LRH group.; Conclusions: LNSRH significantly results in earlier bladder and bowel function after surgery. Limited by sample size, LNSRH should be considered with caution in the future. (© 2021. The Author(s).)

Ma, L., et al. (2022). "A Systematic Review and Meta-Analysis of the Efficacy of Uterine Artery Embolization in the Treatment of Endometriosis." Computational intelligence and neuroscience 2022: 8966063.
	Objective: To compare the efficacy of uterine artery embolization (UAE) with traditional methods for treating endometriosis.; Methods: The randomized controlled trials of uterine artery embolization and other medical treatments for endometriosis in PubMed, Embase, Web of Science, Cochrane Library, China Journal Full-Text Database, Wanfang Database, VIP Database, and China Biomedical Literature Database were retrieved by computer. The search time was up to June 2022. The quality of articles was evaluated by Cochrane ROB 2.0, and meta-analysis was performed by Stata15.1 software.; Results: 7 studies were finally included. Meta-analysis showed that the serum CA125 level after uterine artery embolization was significantly lower than that in the control group (SMD = -0.85, 95%CI (-1.12, -0.59)], and the postoperative visual analogue scale (VAS) of dysmenorrhea was significantly lower than that in the control group (SMD = -1.86, 95%CI (-2.21, -1.50)) There was no significant difference in the effective rate, FSH level, E2 level, and LH level between the two groups.; Conclusion: UAE can effectively reduce the VAS score of dysmenorrhea and serum CA125 level for treating endometriosis. However, due to the limitation of the quality of included articles, more large sample size and high quality RCTs are needed to provide stronger evidence-based medicine evidence for clinical practice.; Competing Interests: The authors declare no conflicts of interest. (Copyright © 2022 Li Ma et al.)

Ma, L. C. and X. L. Nong (2020). "Progress in the study of the anti-tumor mechanism of artesunate." Chinese Journal of Cancer Prevention and Treatment 27(11): 921-926.
	OBJECTIVE: Artesunate is a classical antimalarial drug in China, which has many biological activities, and has some effects on anti-inflammatory, anti angiogenesis, anti immune regulation, anti sepsis and anti-tumor. This study aims to investigate the mechanism and process of anti-tumor of artesunate and provide reference for tumor treatment. METHOD(S): With "artesunate" and "anti-tumor" as the main keywords, the literature published on CNKI, VIP, Wanfang and PubMed databases have been searched from January 1, 2000 to December 20, 2019. Main inclusion criteria: the related pharmacological mechanisms and biological activities of artesunate and its metabolites, and the anti-tumor mechanism of artesunate. Exclusion criteria: repetitive literature and literature review. According to the inclusion exclusion criteria, 46 articles have been included. RESULT(S): Artesunate has a strong cytotoxic effect on tumor cells. The active part of artesunate is a kind of endoperoxide bridge, which produces carbon centered free radicals and oxidative stress during its cleavage. Artesunate has a very good therapeutic effect on liver cancer, lung cancer, gastric cancer, colorectal cancer, ovarian cancer and so on. The main mechanisms of artesunate are inhibition of tumor cell proliferation, induction of tumor cell cycle arrest, induction of tumor cell apoptosis, inhibition of tumor neovascularization, reactive oxygen species mediated cytotoxicity, inhibition of tumor cell invasion and metastasis. Artesunate can also inhibit or kill oral cancer, leukemia, pancreatic cancer, cervical cancer, lymphoma and other cancer cells. Meanwhile, the anti-tumor effect of artesunate has a new research direction, that is, the discovery of regulatory genes, the exploration of signal transduction pathway of tumor cells and the expression of receptors, which need to obtain more experimental and clinical basis. CONCLUSION(S): Artesunate has the characteristics of multi-target and less side effects, which can provide basis for tumor treatment.Copyright © 2020, Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.

Ma, N., et al. (2022). "Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta-analysis." Journal of Clinical Pharmacy and Therapeutics 47(7): 870-878.
	What Is Known and Objective: Reports said immunotherapy is effective for the treatment of idiopathic recurrent miscarriage (RM). Immunotherapy is invasive, and lymphocyte therapy carries some risk of infection. Oral immunosuppressants have the advantages of simple administration and convenience; however, there is no statistical analysis of whether they can improve pregnancy outcomes in patients with idiopathic RM.; Methods: Six databases were searched for studies on oral immunosuppressants and RM; 374 articles were identified. There were two oral immunosuppressants, cyclosporine A and prednisone; two studies were on cyclosporine A and three studies were on prednisone for RM.; Results and Discussion: In total, 554 RM patients were included in this analysis, including 357 patients who received oral immunosuppressive agents and 197 patients who received basic treatment, placebo, or no treatment. Oral administration of cyclosporine A or prednisolone increases live birth rate (OR = 3.6, 95% CI: 2.1-6.15, p < 0.00001) and ongoing pregnancy rate (OR = 8.82, 95% CI: 2.91-26.75, p = 0.0001) in patients with idiopathic RM. Drug use reduced miscarriage rate (OR = 0.21, 95% CI: 0.08-0.52, p = 0.0007); however, there was significant heterogeneity (I 2 = 73%) and a moderate-to-severe risk of bias. There was no effect on premature birth rate (OR = 2.26, 95% CI: 0.96-5.31, p = 0.06). This meta-analysis cannot provide a reference for the duration of medication treatment because the selected studies had inconsistent durations.; What Is New and Conclusion: We did a statistical analysis and found that oral immunosuppressants (including cyclosporine A or prednisolone) can improve pregnancy outcomes in patients with idiopathic RM, increase live birth rate and ongoing pregnancy rate, and reduce miscarriage rate. (© 2022 John Wiley & Sons Ltd.)

Ma, Q., et al. (2020). "Effectiveness of Cotreatment with Kuntai Capsule and Climen for Premature Ovarian Failure: A Meta-Analysis." Evidence-based Complementary and Alternative Medicine 2020: 4367359.
	Objective. To compare the treatment efficacy of Kuntai capsule with Climen only in the therapy of premature ovarian failure. Methods. Randomized controlled trials were electronically retrieved from PubMed, Cochrane Library, Web of science, CBM, CNKI, Wanfang, and Weipu database. In addition, some related papers were manually checked. All papers were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions, and the effective data were analyzed by Revman 5.3 Software. Results. 11 randomized control trials involving 1068 patients were included. Results of meta-analysis showed that E2 Thestrogen), the total therapeutic effective rate of the group of Kuntai capsule, and hormone were higher than hormone only. The LH (luteinizing hormone), FSH (follicle-stimulating hormone), and Kupperman score of the group of Kuntai capsule and Climen were lower than Climen only. Conclusion. Available evidence shows that Kuntai capsule with Climen is more effective than Climen in the therapy of premature ovarian failure. Nowadays, the quality of the research studies is low. More large-scaled randomized trials will need to be carried out.Copyright © 2020 Qianwen Ma et al.

Ma, Q., et al. (2023). "Treatment of Polycystic Ovary Syndrome-Related Infertility Using a Combination of Compound Xuanju Capsules and Hormones: A Meta-Analysis." Alternative Therapies in Health and Medicine 29(2): 271-281.
	Objective: Our aim was to perform a meta-analysis to compare the therapeutic effects of compound Xuanju capsules combined with hormone therapy vs hormone therapy alone in polycystic ovary syndrome (PCOS)-related infertility.; Methods: Electronic databases including PubMed, The Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP database were manually searched. The quality of included studies was evaluated based on Cochrane Systematic Review standards, and the valid data were extracted for meta-analysis using RevMan 5.3 software (Cochrane Review).; Results: A total of 14 randomized controlled trials (RCTs) including 1249 patients were included in the study. Meta-analysis showed that patients in the compound Xuanju capsule + hormone therapy group had higher estradiol (E2) levels and overall rates of effective treatment than patients in the hormone therapy alone group. Moreover, they exhibited lower levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as lower Kupperman scores, than the hormone therapy alone group.; Conclusions: The combination of compound Xuanju capsules and hormone therapy is more effective than hormone therapy alone in the treatment of PCOS-related infertility. However, the quality of current studies is low, and high-quality clinical trials are warranted.

Ma, R., et al. (2021). "The therapeutic effects of glucagon-like peptide-1 receptor agonists and metformin on polycystic ovary syndrome: A protocol for systematic review and meta-analysis." Medicine 100(23): e26295.
	Background: Obesity and insulin resistance (IR) are common in polycystic ovary syndrome (PCOS), which contribute to reproductive and metabolic abnormalities. Metformin increases insulin sensitivity, but it is associated with unsatisfied benefits of weight loss. Recent studies have reported that glucagon-like peptide 1 (GLP-1) receptor agonists improve IR and reduce weight in women with PCOS. We conducted a systematic review and meta-analysis to compare the effects between GLP-1 receptor agonists and metformin, and between GLP-1 receptor agonist-metformin combination and GLP-1 receptor agonists in overweight/obese women with PCOS on anthropometric, metabolic, reproductive outcomes.; Methods: Databases including PubMed, EMBASE, Web of Science, and Cochrane Library were selected to search for randomized controlled trials (RCTs) published in English up to March 2020. Eligible studies were identified according to the inclusion criteria. The primary outcomes included menstrual frequency, body mass index (BMI), total testosterone, and the homeostatic model assessment of insulin resistance. GRADE criteria were implemented to assess the quality of evidence for primary outcomes.; Results: Seven RCTs were selected for analysis, comprising 464 overweight/obese women with PCOS. In the low-quality evidence, a meta-analysis demonstrated that GLP-1 receptor agonists showed better effects relative to metformin on the reduction of body mass index (mean difference - 1.72; 95% confidence interval -2.46 to -0.99, P < .001) and homeostatic model assessment of insulin resistance (standard mean difference -0.37; 95% confidence interval - 0.60,- 0.15, P = .001). Moreover, the combination therapy exhibited similar effects on primary outcomes relative to GLP-1 receptor agonist alone. GLP-1 receptor agonists were also found to be associated with lower abdominal girth compared to metformin. A meta-analysis of gastrointestinal discomfort showed no significant difference between GLP-1 receptor agonist and metformin therapies, and between the combination therapy and GLP-1 receptor agonist alone.; Conclusions: GLP-1 receptor agonists appear to be more beneficial for weight loss and IR improvement compared to metformin for overweight/obese women with PCOS. However, the combination treatment displays comparable effects with GLP-1 receptor agonist alone. The incidence of gastrointestinal discomforts was similar in different groups. However, the quality of the body of evidence is "low." Further prospective RCTs and cost-effectiveness analyses are also warranted to guide GLP-1 receptor agonists to treat women with PCOS.; Competing Interests: The authors report no conflicts of interest. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ma, R., et al. (2019). "Acupuncture for diminished ovarian reserve: Protocol for a systematic review and meta-analysis." Medicine 98(34): e16852.
	Background: The choice of treatments for diminished ovarian reserve (DOR) still remains a challenging clinical problem in reproductive medicine. Acupuncture could be beneficial for patients with DOR. This study aims to systematically investigate the efficacy and safety of the acupuncture for women with DOR.; Methods: We will search electronic databases including PubMed (1946 to present), EMBASE (1974 to present), Cochrane Central Register of Controlled Trials (CENTRAL, all years), Web of Science (1900 to present), Chinese Biomedical Literatures Database (CBM, 1978 to present), China National Knowledge Infrastructure (CNKI, 1979 to present), WANFANG Data (from 2000 to present) to identify potentially eligible studies. Only randomized controlled trials (RCTs) will be included. Experimental interventions include traditional or contemporary acupuncture. Control interventions include no treatment, sham acupuncture, placebo acupuncture, or another active therapy. The primary outcomes include ongoing pregnancy rate and serum anti-Müllerian hormone level. A meta-analysis will be used to estimate a pooled intervention effect if possible.; Results: The results will be published in a peer-reviewed journal.; Conclusion: The findings will provide further evidence for the management of DOR.; Prospero Registration Number: CRD42018114385.

Ma, S., et al. (2023). "Need to clamp indwelling urinary catheters before removal after different durations: a systematic review and meta-analysis." BMJ Open 13(2): e064075.
	Objective This meta-analysis aimed to evaluate the effect of bladder training by clamping on bladder urethral function in patients with indwelling urinary catheters used for different durations. Design Systematic review and meta-analysis. Data sources The UpToDate, Cochrane Library, OVID, PubMed, China National Knowledge Infrastructure, CINAHL and Embase were screened from 1 January 2000 to 28 February 2022. Eligibility criteria for selecting studies Randomised controlled trials (RCTs) or quasi-experimental designs comparing the efficacy of bladder training in patients with an indwelling urinary catheter by clamping or free drainage before urinary catheter removal were published in English or Chinese. Data extraction and synthesis Two reviewers independently extracted the data and assessed the quality of studies. Continuous variables were analysed using mean difference and standardised mean difference (SMD) values with a 95% CI. Categorical variables were analysed using relative risk (RR) and 95% CI. Primary and secondary outcome measures The primary outcome was urinary tract infection incidence, and secondary outcomes included hours to first voiding, incidence of urinary retention and recatheterisation and residual urine volume. Results Seventeen papers (15 RCTs and 2 quasi-RCTs) comprising 3908 participants were included in the meta-analysis. The pooled results of the meta-analysis showed that the clamping group had a significantly higher risk of urinary tract infections (RR=1.47; 95% CI 1.26 to 1.72; p<0.00001) and a longer hour to first void (SMD=0.19; 95% CI 0.08 to 0.29; p=0.0004) compared with the free drainage group. Subgroup analysis of indwelling urinary catheter use durations of <=7 days indicated that clamping significantly increased the risk of urinary tract infection (RR=1.69; 95% CI 1.42 to 2.02, p<0.00001) and lengthens the interval to first void (SMD=0.26, 95% CI 0.11 to 0.41, p=0.0008) compared with free drainage. Conclusions Bladder training by clamping indwelling urinary catheters increases the incidence of urinary tract infection and lengthens the hours to first void in patients with indwelling urinary catheters use durations of <=7 days compared with the free drainage. However, the effect of clamping training on patients with an indwelling urinary catheter use duration of >7 days is unclear.Copyright © 2023 BMJ Publishing Group. All rights reserved.

Ma, T. and Y. Pu (2024). "Effect of Autologous Platelet-Rich Plasma Therapy on the Pregnancy Outcomes of Women with Repeated Implantation Failure: A Systematic Review and Meta-Analysis." Clinical and Experimental Obstetrics and Gynecology 51(2): ceog5102048.
	Background: A major challenge in reproductive medicine is repeated implantation failure (RIF). Possible benefits of platelet-rich plasma (PRP) for pregnancy outcomes are still uncertain, and more evidence is required to properly evaluate this. The current meta-analysis was therefore carried out to assess the impact of intrauterine PRP infusion on pregnancy outcomes in women with RIF. Method(s): Various databases (Web of Science, PubMed, Cochrane Library, Embase) were screened for English-language papers that investigated the effect of PRP treatment on pregnancy outcomes in RIF women who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This effect was analyzed in both frozen-thawed and fresh cycles. These studies involved randomized controlled trial (RCT) and quasiexperimental (non-randomized experimental) studies, but excluded case-control, case series, self-control, cross-sectional studies. The Newcastle-Ottawa Scale was employed to determine study quality. Risk ratios (RRs) were calculated for dichotomous outcome variables, and weighted mean difference (WMD) with 95% confidence interval (95% CI) for continuous outcome variables. These were performed under fixed- or random-effect models. Result(s): This meta-analysis evaluated 15 articles from the literature. Improved pregnancy outcomes were observed in RIF women who received PRP, including higher rates of implantation, clinical pregnancy and live birth compared to control patients. Conclusion(s): The results of this study indicate that PRP could be a useful treatment strategy for RIF patients and those with a thin endometrium. Additional large RCTs are required to identify the subpopulation of women who could derive the maximum benefit from PRP. Copyright © 2024 The Author(s).

Ma, X. H., et al. (2021). "[Efficacy and safety of paclitaxel liposomes compared to paclitaxel combined with platinum in concurrent chemoradiotherapy for unresectable cervical carcinoma: a Meta-analysis]." Zhonghua zhong liu za zhi [Chinese journal of oncology] 43(10): 1132-1139.
	Objective: To explore the efficacy and safety of paclitaxel liposomes compared to paclitaxel with platinum in concurrent chemoradiotherapy for unresectable cervical carcinoma. Methods: SinoMed, CNKI, WanFang MED ONLINE, VIP, PubMed, MEDLINE, Cochrane Library, Embase and ClinicalTrials.gov were searched to collect the papers or clinical studies of paclitaxel liposomes and paclitaxel combined with platinum in concurrent chemoradiotherapy for unresectable cervical carcinoma from the inception to January 15th 2021 in Chinese and English. Two independent reviewers screened the literatures, extracted the data and assessed the bias of the included studies. Meta-analysis was performed using RevMan 5.4 and R software. Results: Totally 9 papers involving 666 patients with unresectable cervical carcinoma were included. The results of meta-analysis indicated that compared to paclitaxel combined with platinum in concurrent chemoradiotherapy for unresectable cervical carcinoma, paclitaxel liposomes combined with platinum exhibited superiority in near-term efficacy (complete response + partial response) [81.4%(272/334) vs 68.7%(228/332), RR =1.19; 95% CI: 1.09, 1.29, P =0.000 1]; substantially decreased the incidence rates of blood system disorders [myelosuppressio, 50.3%(168/334)vs 65.1%(216/332)], gastrointestinal disorders [34.4%(115/334) vs 55.1%(183/332)], alopecia [42.2%(94/223)vs 63.3%(140/221)], allergic reaction [11.6% (23/198)vs 27.6%(54/196), P ≤0.000 1], peripheral neuritis [43.0%(52/121) vs 54.9%(67/122)], or joint and muscle pain [20.3%(16/79) vs 34.6%(28/81), P <0.050 0]. Conclusion: Compared to paclitaxel combined with platinum in concurrent chemoradiotherapy for unresectable cervical carcinoma, paclitaxel liposomes is superior in near-term efficacy, and exhibits better safety.

Ma, X. X. and A. Liu (2019). "Effectiveness of electrical stimulation combined with pelvic floor muscle training on postpartum urinary incontinence." Medicine (United States) 98(10): e14762.
	Background: Previous clinical trials have reported that electrical stimulation (ES) combined with pelvic floor muscle training (PFMT) can be used to treat postpartum urinary incontinence (PPUI) effectively. However, no systematic review has investigated the effectiveness and safety of ES plus PFMT for the treatment of patients with PPUI. In this systematic review, we will firstly assess the effectiveness and safety of ES and PFMT for treating PPUI. Method(s): In this study, we will search the following electronic databases: Cochrane Library, Web of Science, Springer, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inceptions to the present without language restrictions. All eligible randomized controlled trials (RCTs) on the effectiveness of ES plus PFMT for PPUI will be included. We will also search grey literature to avoid missing any other potential qualified studies. Two authors will independently conduct the study selection, data extraction, and risk of bias assessment. A third author will be consulted to solve any disagreements between 2 authors. RevMan 5.3 Software will be used to pool the data and to carry out the meta-analysis. Result(s): This study will provide high quality evidence of ES and PFMT for PPUI. The primary outcome includes symptoms improvement. The secondary outcomes consist of incontinence-specific quality of life, clinician's observations, and adverse effects. Conclusion(s): The findings of this study will summary up-to-dated evidence for judging whether ES combined PFMT is an effective intervention for PPUI or not. Ethics and Dissemination: This study does not needs ethical approval, because it will not involve individual patient data. Its findings will be disseminated through peer-reviewed journals. Copyright © 2019 the Author(s).

Ma, Y.-J., et al. (2021). "Study protocol: a multi-center, double-blind, randomized, 6-month, placebo-controlled trial to investigate the effect of supplementing hormone therapy FET cycles with Gushen'antai pills on the outcomes of in vitro fertilization." Trials 22(1): 657.
	Background: Infertility is a widespread global challenge. Currently, the most effective treatment strategy for infertility is in vitro fertilization (IVF), which is an assisted reproductive technique (ART). The use of IVF for assisted pregnancy dates back to the last 41 years when the first IVF baby was born. During IVF, many oocytes are obtained in an IVF cycle, and more than one embryo is formed. Subsequently, frozen-thawed embryo transfer (FET) is increasingly being used in IVF cycles for women in whom a fresh embryo transfer fails to result in a pregnancy, or in those who return for a second baby. However, the pregnancy success rates following FET treatment cycles are reportedly lower than in fresh embryo transfers. Therefore, recent related studies are increasing determining mechanisms of improving the sustained pregnancy rate of FET and reducing the rate of early abortion. The Gushen'antai pill (GSATP), which contains a mixture of 10 herbs, has been widely used in traditional Chinese medicine (TCM) as a pharmacological option to prevent miscarriage. However, randomized controlled trials (RCT) have never been conducted to provide high-level clinical evidence on the clinical efficacy of GSATP. The objective of this study is to investigate the effect of GSATP of hormone therapy (HT) FET cycles on pregnancy rate.; Methods: A total of 300 subjects aged between 18 and 40 years which prepared for HT cycle FET will be enrolled in the study. The patients were from five different hospitals, with 60 patients from each hospital. Patients were randomly divided into two groups, and medication was started on the day of endometrial transformation. After FET 28 days, B-ultrasound was done to determine whether to continue the medication. Baseline assessments were carried out before the trial and outcomes were collected 4, 6, 8, 10, and 12 weeks of each gestational cycle.; Discussion: Differences in ongoing pregnancy rate, clinical pregnancy rate, implantation rate, and threatened abortion rate between the two groups will be statistically analyzed. We can finally have an objective evaluation of the efficacy of the traditional Chinese medicine Gushen'antai pills.; Trial Registration: ChiCTR1900026737 . Registered October 20, 2019. (© 2021. The Author(s).)

Mabuchi, S., et al. (2023). "Impact of lymphadenectomy in patients with locally recurrent or persistent cervical cancer treated with salvage hysterectomy." The Journal of Obstetrics and Gynaecology Research 49(2): 717-724.
	Aim: To investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy.; Methods: Locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival.; Results: This study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false-negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false-positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3-year postoperative survival rate in this group was 39.7%.; Conclusion: Including LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage. (© 2022 Japan Society of Obstetrics and Gynecology.)

Macchia, G., et al. (2022). "Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(7): 939-943.
	Background: Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer.; Primary Objective: The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment.; Study Hypothesis: Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response.; Trial Design: All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months.; Major Inclusion/exclusion Criteria: The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal.; Primary Endpoint: The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis.; Sample Size: Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions).; Estimated Dates for Completing Accrual and Presenting Results: Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023.; Trial Registration: NCT04593381.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

MacCraith, E., et al. (2021). "Comparison of synthetic mesh erosion and chronic pain rates after surgery for pelvic organ prolapse and stress urinary incontinence: a systematic review." International Urogynecology Journal 32(3): 573-580.
	Background: The aim of this study is to systematically compare rates of erosion and chronic pain after mesh insertion for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) surgery.; Methods: A systematic electronic search was performed on studies that evaluated the incidence of erosion and chronic pain after mesh insertion for POP or SUI. The primary outcome measurement was to compare mesh erosion rates for POP and SUI surgery. Secondary outcome measurements were incidence of de novo pain and a comparison of patient demographics for both surgeries.; Results: Twenty-six studies on 292,606 patients (n = 9077 for POP surgery and n = 283,529 for SUI surgery) met the inclusion criteria. Median follow-up was 26.38 ± 22.17 months for POP surgery and 39.33 ± 27.68 months for SUI surgery. Overall, the POP group were older (p < 0.0001) and had a lower BMI (p < 0.0001). Mesh erosion rates were significantly greater in the POP group compared to the SUI group (4% versus 1.9%) (OR 2.13; 95% CI 1.91-2.37; p < 0.0001). The duration from surgery to onset of mesh erosion was 306.84 ± 183.98 days. There was no difference in erosion rates between abdominal and transvaginal mesh for POP. There was no difference in erosion rates between the transobturator and retropubic approach for SUI. The incidence of chronic pain was significantly greater in the POP group compared to the SUI group (6.7% versus 0.6%) (OR 11.02; 95% CI 8.15-14.9; p < 0.0001). The duration from surgery to onset of chronic pain was 325.88 ± 226.31 days.; Conclusions: The risk of mesh erosion and chronic pain is significantly higher after surgery for POP compared to SUI. These significant complications occur within the first year after surgery.

MacDiarmid, S., et al. (2024). "Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder." Neurourology and Urodynamics 43(1): 31-43.
	Aims: In studies utilizing a 20-injection-site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10-injection-site paradigm targeting the lower bladder. Method(s): In this phase 4, double-blind, parallel-group study, patients with OAB and urinary incontinence (UI) for >=6 months with >=3 episodes of urinary urgency incontinence (no more than 1 UI-free day) and >=8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder. Result(s): Of 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double-blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (-2.9) versus placebo (-0.3) (least squares mean difference [LSMD]: -2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75-50.37]), >=75% (OR: 7.25 [2.00-26.29]), and >=50% improvement (OR: 4.79 [1.87-12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: -2.24, p < 0.0001), nocturia (LSMD: -0.71, p = 0.0004), and urgency (LSMD: -2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23-52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double-blind period; no females used CIC during the double-blind period. Commonly reported adverse events (>=5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo. Conclusion(s): In patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.Copyright © 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

Macdonald, J. A., et al. (2021). "How are you sleeping? Starting the conversation with fathers about their mental health in the early parenting years." Journal of Affective Disorders 281: 727-737.
	Background: Approximately 1 in 10 fathers of infants experience symptoms of common mental health disorders, prompting calls for paternal postpartum screening. However, numerous obstacles exist to screening implementation. The aim of this study was to provide preliminary evidence for an alternative approach that starts with asking fathers about their sleep. Method(s): Using self-reported father data at 0 to 36 months postpartum (N=1204) from four Australian cohort studies, we assessed associations between responses to various single-item questions about sleep (good to poor), and scores on validated measures of mental health (depression, anxiety and stress). We conducted regressions, unadjusted and adjusted for father age, child age, household income, education, first or later child, and marital status, to test associations between sleep and each indicator of mental health. We then meta-analyzed effects and assessed interactions between sleep and each of the covariates. Result(s): Consistent associations between fathers' subjective poor sleep and depression, anxiety and stress were replicated across the four cohorts despite heterogeneity in the sleep questions. At the meta-analytic level, effects ranged from weak to moderate (0.25 to 0.37) and were robust to all adjustments. Interactions were only detected between family income and poor sleep, such that the association was stronger for high income fathers. Limitation(s): This study does not address the sensitivity or specificity of single-item sleep questions for assessing paternal mental health risk. Conclusion(s): A low-cost, non-stigmatizing single question to postpartum fathers about their sleep may present a gateway opportunity to enquiring about mental health.Copyright © 2020

MacGregor, E. A. (2020). "Menstrual and perimenopausal migraine: A narrative review." Maturitas 142: 24-30.
	Migraine is affected by the changing hormone environment, with perimenopause associated with increased migraine, particularly menstrual migraine. Menstrual attacks are recognised to be more disabling and less responsive to treatment compared with non-menstrual attacks. Perimenstrual estrogen 'withdrawal' is implicated in the pathophysiology of menstrual migraine, with increased prevalence of migraine in perimenopause associated with unpredictable estrogen fluctuations. Perimenopausal women often have contraceptive needs as well as menopause symptoms and it is important to understand the potential effects of exogenous hormones on migraine. Maintaining stable estrogen levels with exogenous hormones can benefit migraine but clinical trial data are limited. This short narrative review addresses the diagnosis and management of menstrual migraine in perimenopausal women, and discusses the management of menopause symptoms in peri- and postmenopausal women with migraine.Copyright © 2020

Machado, A. C., et al. (2023). "Applicability of vaginal energy-based devices in urogynecology: evidence and controversy." Revista da Associacao Medica Brasileira (1992) 69(suppl 1): e2023S2129.
	OBJECTIVE: This study aimed to analyze the evidence and controversies about the use of vaginal energy-based devices (laser and radiofrequency) for treatment of genitourinary syndrome of menopause, recurrent urinary tract infection, urinary incontinence, and genital prolapse through a literature review. METHODS: A search of literature databases (PubMed, Medline) was performed for publications in December 2022. Keywords included genitourinary syndrome of menopause, vaginal laxity, vaginal/vulvovaginal atrophy, urinary tract infection, urgency incontinence, frequency, urgency, stress urinary incontinence, genital prolapses AND energy-based devices, AND vaginal laser, AND vaginal radiofrequency, AND CO2 laser, AND Er:YAG laser. Publications in English from the last 7 years were reviewed and selected by the authors. RESULTS: The literature regarding vaginal energy-based devices in the treatment of urogynecological conditions is primarily limited to prospective case series with small numbers and short-term follow-up. Most of these studies showed favorable results, improvement of symptoms with low risk, or no mention of serious adverse events. Consensus statement documents from major medical societies suggest caution in recommending these therapies in clinical practice until more relevant data from well-designed studies become available. CONCLUSION: The potential of the vaginal laser and radiofrequency as a therapeutic arsenal for the evaluated urogynecological conditions is great, but qualified research must be done to prove their efficacy and long-term safety, define application protocols, and recommend the use of these technologies in clinical practice.

Mackens, S., et al. (2022). "Oral dydrogesterone (OD) versus micronized vaginal progesterone (MVP) for luteal phase support (LPS): impact on endometrium and genital tract microbiota." Human reproduction (Oxford, England) 37: i150.
	Study question: Is there a difference in the endometrial transcriptome and/ or reproductive tract microbiota composition when OD versus MVP is used as LPS for fresh embryo transfer? Summary answer: Endometrial transcriptome signatures and microbiota composition at the vaginal, cervical or intra‐uterine site presented no significant differences following OD versus MVP. What is known already: Adequate LPS is crucial to achieve a successful pregnancy following ovarian stimulation (OS) and fresh embryo transfer. OD has been proven to be non‐inferior compared to MVP in two phase III clinical RCTs. Additionally, a combined individual participant data and aggregate data meta‐analysis showed an odds ratio in favor of OD for live birth. Little information is available on the potential differences at the molecular level of the reproductive organs following the administration of either LPS strategies. Given the potential immunomodulating properties of OD, of main interest is the endometrial functionality and microbiota composition of the female genital tract. Study design, size, duration: Thirty oocyte donors were planned to have two OS‐cycles followed by one week of LPS (OD or MVP) in a randomized, cross‐over, double‐blind, double‐dummy fashion. An endometrial biopsy, as well as vaginal/cervical/intra‐uterine samples were collected. Endometrial RNA‐sequencing was performed, raw reads were processed using STAR/ htseq‐count, differential gene expression was evaluated with EdgeR. Microbiota profiles were obtained by 16S‐rRNA‐sequencing using the DADA2‐pipeline with RDP‐classifier. Comparative analysis of genera relative abundances was performed in R. Participants/materials, setting, methods: All oocyte donors were <35 years old, had regular menstrual cycles, no intra‐uterine contraceptive device, AMH within normal range and BMI≤ 29 kg/m2. OS was performed in a GnRH antagonist protocol followed by dual triggering (1000U hCG + 0.2mg triptorelin) as soon as≥3 follicles of 20mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg (Utrogestan®) or OD 10 mg (Duphaston® ), both three times daily. Main results and the role of chance: Subject and stimulation characteristics were comparable between the groups. For endometrial RNA‐sequencing, 21 pairs (n=42 biopsies) were available with the same oocyte donor having a biopsy after OD as well as after MVP (the remaining 9 subjects were excluded due to late follicular progesterone elevation/drop‐out after one cycle). After correction for multiple hypothesis testing, no differentially expressed genes could be withheld and the principal component analysis plot showed one mixed OD/MVP cluster (PCA1 25% variance, PCA2 16% variance). The average Euclidean distance between samples of the OD group was significantly lower than for the MVP group (respectively 12.1 vs 18.8, comparison of the two‐group wise Euclidean distributions results in p=6.98e‐14 using the Mann‐Whitney test). Microbiota profiling was performed before and after OD/MVP (4 collections per subject). Samples with insufficient high‐quality reads were excluded, resulting in 42 intra‐uterine samplings, 82 cervical and 84 vaginal swabs used for analysis. No difference was seen at any site of the female reproductive tract following OD versus MVP in microbiota diversity, richness, genera abundances (delta contrasts [Mann‐Whitney U test], padj > 0.1), nor community composition (dbRDA genus‐level Euclidean distances in vagina [R2= 0.22%, padj=0.26], cervix [R2= 0.36%, padj=0.20], uterus [R2= ‐0.06%, padj=0.45]). Limitations, reasons for caution: Sample size was limited. Whole tissue endometrial transcriptomics was performed on individual biopsies without accounting for the potential bias of different tissue compartment compositions among biopsies. As it was a double blind, double dummy study design, the impact of not administering medication via the vaginal route could not be evaluated. Wider implications of the findings: This is the first molecular t dy comparing OD/MVP. Results show that there is no difference between OD/MVP's ability to give rise to the receptive state, which corresponds with the clinical trial data. As the inter‐sample distance of RNA‐profiles was smaller following OD, interindividual variations could be lower for this approach.

Mackenzie, S., et al. (2023). "Fertility and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate." Human Reproduction 38(Supplement 1): i440-i441.
	Study question: What are the future fertility prospects and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate? Summary answer: Pregnancy post-ectopic pregnancy occurred in 53% of women within 12 months following methotrexate treatment. Among those who became pregnant, ectopic pregnancy recurrence occurred in 16.8%. What is known already: Concerns regarding ectopic pregnancy recurrence and future fertility predominate when counselling women about management options for tubal ectopic pregnancy treatment. Current UK National Institute for Health and Care Excellence guidance is based on low quality evidence and estimate long-term ectopic pregnancy recurrence rate of >=18.5%. Further, they state that there are no differences in rates of subsequent pregnancy or ectopic pregnancy recurrence between ectopic pregnancy management methods. However, 30% of women managed with methotrexate experience treatment failure and require rescue surgery and subsequent pregnancy outcomes in this group are poorly understood. Study design, size, duration: The data for this study were derived from a UK multicentre RCT of methotrexate and gefitinib versus methotrexate and placebo for treatment of ultrasound diagnosed definite or probable tubal ectopic pregnancy with pre-treatment hCG <=1000 IU/L and >=5000 IU/L (GEM3). The trial found adding gefitinib to methotrexate was not superior to placebo. This analysis reports trial participant follow-up data at 12-months examining post-treatment fertility, subsequent pregnancy outcomes and participant characteristics associated with ectopic pregnancy recurrence. Participants/materials, setting, methods: Trial participants of GEM3 (as described above). Participants were contacted to provide follow-up data 12 months after randomisation to treatment. Where telephone contact was unsuccessful, electronic health records were reviewed to collect pregnancy outcome data. Post-treatment fertility and pregnancy outcomes were summarised using descriptive statistics and compared between groups using a chi-squared test, p<.05 signified statistical significance. Main results and the role of chance: Pregnancy follow-up data was obtained for 283/327 trial participants. (167 participants were successfully contacted by telephone; the electronic health records were reviewed for 116 participants). 52.7% (149/283) of the trial participants became pregnant in the 12-month follow-up period. There was no difference in subsequent pregnancy rates between 'methotrexate only' and 'methotrexate and rescue surgery' groups. The surgical approach (salpingectomy vs salpingotomy) did not affect subsequent pregnancy rates. Among women who had a pregnancy in the follow-up period, a live birth was recorded in 65% of women (n=93/ 142, n=7 missing), any pregnancy loss (miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy or molar pregnancy) was recorded in 43% of women (n=59/137, n=12 missing). Recurrent ectopic pregnancy was reported in 16.8% of women (n=22/131, n=18 missing). There was no difference in rates of live birth, pregnancy loss or recurrent ectopic pregnancy between methotrexate only and methotrexate and surgery groups or between type of surgical management groups (salpingectomy vs salpingotomy). Limitations, reasons for caution: This study only reports on a 12-month follow-up period and this should be considered when interpreting comparatively low post-treatment pregnancy rates. We did not record which couples were trying-to-conceive post treatment and were therefore unable to stratify results by this variable or report subfertility rates. Wider implications of the findings: This prospective dataset strengthens current understanding of the likelihood of ectopic pregnancy recurrence. Furthermore, it provides reassurance that women with tubal ectopic pregnancy managed with methotrexate requiring rescue surgery have similar posttreatment fertility and pregnancy outcomes to those successfully treated with methotrexate.

MacKinnon Anna, L., et al. (2021). "Effects of mindfulness-based cognitive therapy in pregnancy on psychological distress and gestational age: Outcomes of a randomized controlled trial." Mindfulness 12(5): 1173-1184.
	Objectives: Given stress, anxiety, and depression affect 15-25% of women during pregnancy and are associated with adverse outcomes for maternal and child health if untreated, a randomized controlled trial evaluated the effectiveness of an 8-week modified Mindfulness-Based Cognitive Therapy for Perinatal Depression (MBCT-PD) intervention for psychological distress. Methods: A community sample of pregnant women who self-identified as experiencing high levels of psychological distress was randomized into MBCT-PD (n = 28) or treatment as usual (n = 32). Participants completed online questionnaires assessing symptoms of distress, pregnancy and generalized anxiety, depression, and stress during lab visits at enrolment (before allocation), immediately following the intervention, and at follow-up (3 months postpartum). Women also reported delivery type and gestational age of their newborn. Results: Using an intention-to-treat approach, multilevel modeling indicated a significant effect of MBCT-PD treatment on overall psychological distress, but not on other symptoms. Path analysis revealed a moderated mediation, with an indirect effect of MBCT-PD treatment on lengthening gestational age through decreasing pregnancy anxiety among women with higher baseline symptoms. Conclusions: In pregnant women seeking treatment for high levels of psychological distress, MBCT-PD was associated with improved overall distress, but not other specific symptoms such as anxiety and depression beyond treatment as usual. MBCT-PD has the potential to reduce the risk of preterm birth by targeting and reducing high levels of pregnancy anxiety during early gestation. Further research is warranted to examine other outcomes (e.g., coping skills, interpersonal functioning) and comparisons to other interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Macquarie, U. (2022). "Self-management and self-efficacy in endometriosis." ANZCTR.
	
Madariaga, A., et al. (2023). "Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma." Nature communications 14(1): 1452.
	This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16-53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity. (© 2023. The Author(s).)

Madariaga, A., et al. (2022). "Patient self-reporting of tolerability using PRO-CTCAE in a randomized double-blind, placebo-controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in patients with platinum resistant or refractory epithelial ovarian carcinoma." Gynecologic Oncology 167(2): 226-233.
	Background: A double-blind, randomized, placebo-controlled, phase 2 trial assessed gemcitabine in combination with the wee1 inhibitor adavosertib or placebo in platinum resistant or refractory high grade serous ovarian cancer (HGSOC), demonstrating improved progression free and overall survival favouring the adavosertib/gemcitabine arm. An exploratory objective of the study included the PRO-CTCAE assessment, to capture self-reporting of frequency, severity and/or interference of symptomatic adverse events (syAEs).; Methods: PRO-CTCAE items at baseline, days 1 and 15 of each cycle and off treatment, were completed in two centres, with the objective of characterizing syAEs in the first three months of therapy. The maximum post-baseline score proportion for each syAE was tabulated per patient. The 12-week area under the curve (AUC12w) as a measure of syAE over-time and incremental AUC12w (iAUC12w) for adjustment to baseline syAEs.; Results: Sixty-one patients were approached for PRO-CTCAE surveys and 55 were evaluable. Among patients with HGSOC, 28 received gemcitabine/adavosertib (arm A) and 19 gemcitabine/placebo (arm B). Survey completion rates were high. The proportion of participants with positive (≥1) PRO-CTCAE scores was higher for difficulty swallowing with gemcitabine/adavosertib (arm A 35.7% vs arm B 5.3%, p = 0.02). The high score (≥3) syAEs showed more frequent diarrhea with gemcitabine/adavosertib (arm A 25% vs arm B 0%, p = 0.03). The proportions of worsening syAEs over time were higher in patients receiving gemcitabine/adavosertib for difficulty swallowing (arm A 35.7% vs arm B 5.3%; p = 0.03) and fatigue severity (arm A 71.43% vs arm B 42.1%; p = 0.04).; Conclusions: The longitudinal assessment of patient self-reported tolerability showed greater difficulty swallowing and fatigue severity in patients receiving gemcitabine/adavosertib, compared to gemcitabine/placebo. PRO-CTCAE provides complementary and objective assessment of drug tolerability from a patient's perspective. (Copyright © 2022. Published by Elsevier Inc.)

Madi Jose, M., et al. (2022). "Perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia: a systematic review of observational studies and meta-analysis." American Journal of Obstetrics and Gynecology 226(5): 633.
	Objective: To assess perinatal outcomes of first pregnancy after remission from gestational trophoblastic neoplasia and the impact of the time between the end of chemotherapy and the subsequent pregnancy.; Data Sources: The Medical Subject Headings related to perinatal outcomes, chemotherapy, and gestational trophoblastic neoplasia were used alone or in combination to retrieve relevant articles. We searched all references registered until April, 2019 in Embase, LILACS, MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science.; Study Eligibility Criteria: We included any observational or interventional studies that evaluated perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia. Animal studies, narrative reviews, expert opinions, and previous treatments with potential risks for future perinatal outcomes which may introduce confounding bias were excluded.; Study Appraisal and Synthesis Methods: Two reviewers independently screened all identified references for eligibility and data extraction. Methodological quality and bias of included studies were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institutes of Health. For the meta-analysis, the measures of association were calculated using bivariate random-effects models. Statistical heterogeneity was evaluated with I 2 statistics and explored through sensitivity analysis. Publication bias was assessed by visual inspection of the funnel plot or Egger's test, according to the number of articles included. For all analyses, a P value of <.05 indicated statistical significance. This study was registered on PROSPERO (CRD42018116513).; Results: A total of 763 studies were identified after literature search and 23 original studies were included in the systematic review and in the meta-analysis. The combined data from the subgroup meta-analysis (outcome vs time after chemotherapy) showed an incidence of spontaneous abortion of 15.28% (95% confidence interval, 12.37-18.74; I 2 =73%), 3.30% of malformation (95% confidence interval, 2.27-4.79; I 2 =31%), 6.19% of prematurity (95% confidence interval, 5.03-7.59; I 2 =0), and 1.73% of stillbirth (95% confidence interval, 1.17-2.55; I 2 =0%). These results were not influenced by the time between the end of chemotherapy and the subsequent pregnancy in most of the studied outcomes, including malformation (P=.14, I 2 =31%), prematurity (P=.46, I 2 =0), and stillbirth (P=.66, I 2 =0). However, there was a higher occurrence of spontaneous abortion (P<.01, I 2 =73%) in pregnancies that occurred ≤6 months after chemotherapy.; Conclusion: Chemotherapy for gestational trophoblastic neoplasia does not appear to increase the chance of unfavorable perinatal outcomes, except for the higher occurrence of spontaneous abortion in pregnancies occurring ≤6 months after chemotherapy. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Madorra (2021). Non-hormonal Medical Device for Treatment of Vulvovaginal Atrophy (VVA) in Post-Menopausal Women.
	No Results Available Device: Non-hormonal vaginal device therapy|Device: Sham vaginal device therapy Clinician Assessed Changes in VVA|Patient Reported VAS Score|Responder Rate PGI-I Female Not Applicable 25 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment CLN-201 August 22, 2022

Madrid Universidad Complutense, d. and d. Salamanca Universidad Pontificia (2023). Maternal Well-being in the Postnatal Stage.
	No Results Available Behavioral: Positive Psychology Intervention|Behavioral: Cognitive Behavior Therapy Postpartum depression change|Positive and Negative Affect change|Satisfaction with life change (SWLS). Scores range from 5 to 35, where higher scores mean a better outcome.|Beliefs about pregnancy change|Psychological well-being change|Maternal filial bond in the postpartum change|Maternal self-efficacy change Female Not Applicable 98 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment UCM-UPS-WELLBEING June 2024

Maeda, M., et al. (2022). "Primary Fallopian Tube Carcinoma Presenting with a Massive Inguinal Tumor: A Case Report and Literature Review." Medicina (Kaunas, Lithuania) 58(5).
	Primary fallopian tube carcinoma (PFTC) has characteristics similar to those of ovarian carcinoma. The typical course of PFTC metastasis includes peritoneal dissemination and pelvic and paraaortic lymph node metastasis, while inguinal lymph node metastasis is rare. Moreover, the initial presentation of PFTC with an inguinal tumor is extremely rare. A 77-year-old postmenopausal woman presented with a massive 12-cm inguinal subcutaneous tumor. After tumor resection, histopathological and immunohistochemical analysis showed that the tumor was a high-grade serous carcinoma of gynecological origin. Subsequent surgery for total hysterectomy with bilateral salpingo-oophorectomy revealed that the tumor developed in the fallopian tube. She received adjuvant chemotherapy with carboplatin and paclitaxel, followed by maintenance therapy with niraparib. There has been no recurrence or metastasis 9 months after the second surgery. We reviewed the literature for cases of PFTC and ovarian carcinoma that initially presented with an inguinal tumor. In compliance with the Preferred Reporting Items for Systematic Reviews guidelines, a systematic literature search was performed through 31 January 2022 using the PubMed and Google scholar databases and identified 14 cases. In half of them, it was difficult to identify the primary site using preoperative imaging modalities. Disease recurrence occurred in two cases; thus, the prognosis of this type of PFTC appears to be good.

Maffei, S., et al. (2022). "Long-term effects of a combination of isoflavones, agnus castus and magnolia extracts on climacteric symptoms and cardiometabolic risk profile in postmenopausal women." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(4): 339-344.
	Objective: To evaluate the long-term effects of a combination of isoflavones, agnus castus and magnolia extracts (combined isoflavone compound [CIC]) on climacteric symptoms and cardiometabolic risk in symptomatic postmenopausal women.; Methods: This interventional, prospective study evaluated climacteric symptoms, mood and sleep disorders using the 21-item Greene Climacteric Scale (GCS) and 7-item Insomnia Severity Index (ISI) questionnaires; and cardiovascular, metabolic and thrombotic risk markers at baseline (T0) and after 12 months of CIC treatment (T1).; Results: In healthy postmenopausal women ( N = 71), 12-month CIC treatment significantly reduced patient-reported vasomotor symptoms (100% vs. 17%), mood disorders (67% vs . 25%) and sleep disorders (89% vs. 19%%) (all p < .001) compared with baseline; and significantly improved GCS psychological, somatic, and vasomotor domain scores and ISI sleep disturbance scores (all p < .05). CIC significantly reduced systolic ( p = .022) and diastolic blood pressure ( p < .001), and heart rate ( p < .001); glucose concentrations ( p = .018), HOMA index ( p = .013), and ALT ( p = .035), homocysteine ( p = .005) and NT-proBNP ( p = .003) levels.; Conclusions: Long-term CIC therapy improved vasomotor symptoms, mood disorders, sleep disorders, hemodynamic measurements and cardiometabolic risk markers in healthy postmenopausal women.; Clinicaltrials.gov Identifier: NCT03699150.

Magarakis, L., et al. (2023). "SALpingectomy for STERilisation (SALSTER): study protocol for a Swedish multicentre register-based randomised controlled trial." BMJ Open 13(9): e071246.
	Introduction: Salpingectomy is currently suggested as an alternative to tubal ligation for sterilisation. Precursor lesions of ovarian carcinoma can be found in the fallopian tubes; thus, salpingectomy could possibly reduce the incidence. Most of the existing trials on safety are small, on caesarean section and report on surrogate ovarian function measures. Randomised trials in laparoscopy are lacking. Well-designed trials are needed to evaluate safety of laparoscopic opportunistic salpingectomy.; Methods and Analysis: In SALSTER, a national register-based randomised controlled non-inferiority trial, 968 women <50 years, wishing laparoscopic sterilisation will be randomised to either salpingectomy or tubal ligation. The Swedish National Quality Register of Gynecological Surgery (GynOp) will be used for inclusion, randomisation and follow-up. Primary outcomes are any complication up to 8 weeks postoperatively, and age at menopause . Both outcomes are measured with questionnaires, complications are also assessed by a gynaecologist. In a nested trial, ovarian function will be evaluated comparing the mean difference of anti-Müllerian hormone (AMH), assessed preoperatively and 1 year after surgery.; Ethics and Dissemination: Performing salpingectomy for sterilisation has become increasingly common, despite the unclear risk-benefit balance. SALSTER studies the safety of salpingectomy compared with tubal ligation. Regardless of the result, SALSTER will provide gynaecologists with high quality evidence to inform women to decide on salpingectomy or not. The central ethical review board of Gothenburg, Sweden (Dnr. 316-18) approved the trial in 2018. Results will be presented at scientific congresses and published in peer-reviewed scientific journals. The results will be communicated through professional organisations and research networks.; Trial Registration Number: NCT03860805.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Magarelli Paul, C., et al. (2023). "The birth of integrative reproductive medicine: finally, a randomized controlled trial for endometriosis treated with acupuncture!" Fertility and Sterility 119(5): 824-825.
	
Maged Ahmed, M., et al. (2023). "The value of platelet-rich plasma in women with previous implantation failure: a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics 40(5): 969-983.
	Objective: To assess the value of intrauterine PRP to improve IVF outcome in women with previous implantation failure.; Methods: Screening of Pubmed, Web of Science, and other databases from inception to August 2022 using the keywords related to "platelet-rich plasma" OR "PRP" AND "IVF" "implantation failure." Twenty-nine studies (3308 participants) were included in our analysis, 13 were RCTs, 6 were prospective cohorts, 4 were prospective single arm, and 6 were retrospective analyses. Extracted data included settings of the study, study type, sample size, participants' characteristics, route, volume, timing of PRP administration, and outcome parameters.; Results: Implantation rate was reported in 6 RCTs (886 participants) and 4 non-RCTs (732 participants). The odds ratio (OR) effect estimate was 2.62 and 2.06, with 95% CI of 1.83, 3.76, and 1.03-4.11, respectively. Endometrial thickness was compared in 4 RCTs (307 participants) and 9 non-RCTs (675 participants), which showed a mean difference of 0.93 and 1.16, with 0.59-1.27 and 0.68-1.65 95% CI, respectively.; Conclusion: PRP administration improves implantation, clinical pregnancy, chemical pregnancy, ongoing pregnancy, live birth rates, and endometrial thickness in women with previous implantation failure. (© 2023. The Author(s).)

Maged, A. M., et al. (2021). "Endometrial scratch injury in infertile women seeking conception through natural or intrauterine insemination cycles. A systematic review and meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.
	BACKGROUND: Implantation failure is a major cause of infertility OBJECTIVE: To evaluate the value of ESI in infertile women undergoing natural or IUI cycles. SEARCH STRATEGY: Screening of MEDLINE, CENTRAL, other bases from inception to June 2021 using the keywords related to endometrial scratch, implantation, infertility, and IUI. SELECTION CRITERIA: RCTs of intentional endometrial injury in couples seeking fertility through natural or IUI cycles were included. All types of ESI with variable intensity (mild to moderate or severe), at different times of the cycle (preceding follicular, preceding luteal, same follicular or two times), single or double compared to none , placebo or other active interventions were included. Twenty-five studies included 4234 women [5 natural (774 women), 20 IUI (3460 women)] fulfilled the inclusion criteria. DATA COLLECTION AND ANALYSIS: Extracted data included settings of the study, sample size, participants characteristics, intervention details and outcome parameters. The primary outcome was the clinical pregnancy rate. RESULTS: ESI increased clinical pregnancy rate from 16.1 % (62/386) to 26.5% (103/388) and from 11.4 % (186/1627) to 22.25% (408/1833), P value = 0.004 and <0.001 in natural and IUI cycles respectively. ESI increased live birth rate from 26.6 % (42/158) to 37.6 % (59/157) (P = 0.250) and from 11.2 % (36/322) to 18 % (58/322) (P = 0.020) in natural and IUI cycles respectively. CONCLUSION: ESI increased both clinical pregnancy and ongoing pregnancy rates significantly in natural and IUI cycles. However, there is marked methodological heterogeneity among the different studies in defining the outcome parameters.

Maggen, C., et al. (2019). "Management of cancer during pregnancy and current evidence of obstetric, neonatal and pediatric outcome: A review article." International Journal of Gynecological Cancer 29(2): 404-416.
	The diagnosis of cancer during pregnancy imposes a medical-ethical dilemma in weighing the risks of both mother and child. Increasing awareness of the feasibility of chemotherapy during pregnancy results in more pregnant patients receiving treatment for cancer. Information on obstetric and pediatric outcome of these high-risk pregnancies is greatly needed to guide physicians in patient counseling. In this review we present reported evidence for the incidence, diagnostic options, therapeutic management, obstetric risks, and neonatal outcome when cancer treatment is initiated during pregnancy. Decision-making when a cancer is diagnosed in a pregnant patient should be multidisciplinary, always taking the patient's perspective into account. Cancer treatment during pregnancy is associated with low birth weight and preterm delivery, therefore frequent obstetric follow-up during oncological treatment in a specialized center is mandatory. Short-Term clinical, cardiac, and cognitive outcome of children pre-natally exposed to cancer treatment is overall reassuring. Long-Term follow-up of children is warranted to define the possible effect of pre-natal cancer treatment on general health, fertility outcome, and the risk of secondary cancers.Copyright © IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Maghalian, M., et al. (2022). "The Effect of Melissa officinalis on Premenstrual Syndrome and Primary Dysmenorrhea in Women of Reproductive Age: A Systematic Review and Meta-Analysis." Current Women's Health Reviews 18(3): 25-36.
	Background: Premenstrual syndrome (PMS) and dysmenorrhea are prevalent disabling conditions and affecting the quality of life of women of reproductive age. Melissa officinalis ex-hibits multiple pharmacological properties, including anti-inflammatory, antispasmodic, analgesic, and antidepressant activities. Objective(s): The aim of this study was to systematically review the effect of Melissa officinalis on PMS and primary dysmenorrhea. Method(s): A systematic search in English (Embase PubMed, ProQuest, Scopus, Clininaltrial.gov, Cochrane Library), and Persian (SID, Magiran, Iran Doc) databases to find articles was carried out in May 2020. All types of clinical trials were included. Two authors independently selected the articles and quality assessments and extracted the data. Standardized Mean Difference (SMD) was de-scribed as a measure of effect size due to the application of multiple tools to measure the severity of PMS. The quality of evidence was assessed using the GRADE approach. Result(s): A total of 978 articles were obtained from databases. Ultimately, 7 articles were included in the study. Based on the results of these 7 studies, the consumption of Melissa officinalis improved the symptoms of PMS and primary dysmenorrhea after treatment, as compared to the control group. Also, from the meta-analysis results, the consumption of Melissa officinalis in the intervention group as compared to the control group, significantly reduced the mean severity of PM-S's symptoms following treatment) SMD:-0.93; 95% CI:-.19 to-0.67; P=0. 88; I2=0%). Conclusion(s): Due to the limited number of articles included in the meta-analysis, conducting wel-l-designed clinical trials with large sample size to ascertain the effect of Melissa officinalis on PMS and primary dysmenorrhea are recommended.Copyright © 2022 Bentham Science Publishers.

Magrina, J., et al. (2021). "Nerve-sparing in Gynecologic Surgery: A Perspective." Journal of Minimally Invasive Gynecology 28(3): 475-480.
	Objective: To provide a perspective on nerve-sparing (NS) surgery in gynecology.; Data Sources: Literature review, English language.; Methods of Study Selection: Systematic reviews and meta-analyses studies were selected for review for oncology; comparative studies were selected for endometriosis, and 1 comparative and 1 prospective study were chosen for sacrocolpopexy.; Tabulation, Integration, and Results: Two tables summarize the results of systematic reviews and meta-analyses in oncology. Oncology, endometriosis, and urogynecology sections. Primary benefit of NS technique is decreased bladder dysfunction, and, to a lesser degree, vaginal and rectal dysfunc.; Conclusion: NS is preferable to conventional surgery for benign and malignant conditions to reduce postoperative bladder, rectal, and vaginal dysfunction. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Mah, S. J., et al. (2022). "THE EFFICACY OF SECOND CURETTAGE IN THE TREATMENT OF LOW-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS." International Journal of Gynecological Cancer 32(Supplement 3): A218.
	Objectives Patients with low-risk gestational trophoblastic neoplasia (GTN) are almost universally cured with chemotherapy, but second uterine curettage has been explored as an alternative to avoid chemotherapy-related toxicities. We systematically reviewed intervention studies to determine whether second curettage in patients with low-risk GTN affects: 1) the proportion of patients requiring chemotherapy; 2) the number of chemotherapy cycles; and 3) the need for multi-agent chemotherapy. Methods A literature search was performed including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science. Two authors screened titles, abstracts, and full texts and abstracted data. Risk of bias was assessed for each outcome. Data were pooled using a randomeffects model and assessed for heterogeneity. Quality of evidence was assigned using GRADE. Results Six studies met inclusion criteria; 2 randomized studies (RCT) and 4 non-randomized studies (NRS). Mean difference in number of chemotherapy cycles was 2.04 fewer in patients who underwent second curettage (95% CI -5.00 to 0.91) based on two pooled RCTs (N=138). Those who underwent second curettage had RR=0.60 (95% CI 0.31 to 1.18) for requiring chemotherapy based on 4 pooled NRS (N=1105), and RR=1.17 (95% CI 0.76 to 1.80) for multi-agent chemotherapy based on two pooled NRS (N=900). The certainty of evidence is very low due to risk of bias for potential confounding, selection bias, missing data, and inconsistency of the results. Conclusions Second curettage may reduce the need for chemotherapy in patients with low-risk gestational trophoblastic neoplasia but the evidence is very uncertain.

Maharajan, K., et al. (2021). "Therapeutic importance of the Zishen Yutai Pill on the female reproductive health: A review." Journal of Ethnopharmacology 281: 114523.
	ETHNOPHARMACOLOGICAL RELEVANCE: Zishen Yutai Pill (ZYP) is a widely used Traditional Chinese Medicine in Assisted Reproductive Technology (ART) medications, particularly in China. ZYP has a potential therapeutic role in human reproductive health, including in vitro fertilization embryo transfer and various reproductive disorders. The National Essential Medicine List of China has recently included the ZYP in Obstetrics and Gynecology medicine due to its significance in treating miscarriage and fertility associated disorders. Various clinical studies have demonstrated the importance of ZYP in improving the fertility and pregnancy rate. However, the pharmacological and toxicological actions of ZYP in ART and reproductive health is yet to be addressed. AIM OF THE REVIEW: This review aims to emphasize the potential therapeutic effect of ZYP in ART and highlight its clinical significance in treating various reproductive disorders linked with hormonal balance, follicle development, menstrual cycle, uterine function and pregnancy. Additional insights on the safety evaluation of ZYP were elucidated by exploring an array of published experimental studies in various animal models with its molecular mechanism of action. MATERIALS AND METHODS: The literature review was conducted across the databases such as PubMed, ScienceDirect, Google Scholar, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, International Clinical Trials Registry Platform and Cochrane Central Register of Controlled Trials with no time limit applied. The search terms used in this review include, 'Zishen Yutai Pills' and/or 'reproduction', 'assisted reproductive techniques', 'pregnancy', 'threatened abortion', 'miscarriage', 'fertility', 'infertility', 'disorders', 'women health', 'toxicity', and 'adverse effects'. RESULTS: ZYP is a combination of fifteen traditional medicines and each of its components has various biological functions in humans. ZYP has improved the fertility and pregnancy rate through in vitro fertilization-embryo transfer. Further, various clinical studies have revealed that ZYP has the curative effect for miscarriage, recurrent spontaneous abortion, menstrual disorder, luteal dysfunction, diminished ovarian reserve, polycystic ovary syndrome and premature ovarian insufficiency. The intervention of ZYP has multiple roles in reproductive functions such as regulation of ovulation, menstrual flow, follicle development, hormonal balance and endometrial thickness. The reproductive and toxicological reports in various animal models have highlighted the efficacy and safety of ZYP on the reproductive functions. CONCLUSION: Nowadays, many problems are associated with maternal health, fertility and reproduction due to the various physiological and environmental factors. The intervention of ART provides hope to infertile patients. Overall, this review provides insights on the therapeutic importance of ZYP in ART medications and the treatment of reproductive disorders in humans.

Maharjan Dhruba, T., et al. (2021). "Testosterone in Female Depression: A Meta-Analysis and Mendelian Randomization Study." Biomolecules 11(3).
	Testosterone's role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.

Mahboubi, M. (2019). "Foeniculum vulgare as Valuable Plant in Management of Women's Health." Journal of Menopausal Medicine 25(1): 1-14.
	This review paper evaluates use of Foeniculum vulgare extracts as a popular female plant in management of different ailments of women. Information in this paper was gathered from accessible sources (PubMed, Science Direct, Springer, Wiley, and Google), and traditional books (Persian or English modern traditional books), unpublished data (R&D reports, thesis and dissertation) by keywords based on the words F. vulgare or fennel and women. Efficacy of oral fennel oil in management of dysmenorrhea, premenstrual syndrome, amenorrhea, menopause, lactation, and polycystic ovary syndrome were confirmed according to results of clinical studies. Results of clinical efficacy of fennel oil on menstrual bleeding is complicated, but results of one meta-analysis study revealed that fennel oil significantly increased means of bleeding in the first menstrual periodic cycle ( P = 0.001), while fennel oil had no significant effect on bleeding in the second menstrual cycle ( P = 0.67). Topical and vaginal fennel extract (5%) exhibited good efficacy in treatment of sexual function, vaginal atrophy, and hirsutism. Fennel had no effect on bone density, or body mass index of menopause women. Results of clinical studies introduce fennel as a valuable medicinal plant in management of women's ailments, but understanding the mechanism of action could be the subject of future studies.; Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Mahdy, A. and G. M. Ghoniem (2019). "Autologous rectus fascia sling for treatment of stress urinary incontinence in women: A review of the literature." Neurourology and Urodynamics 38(S4): S51-S58.
	Aims: Stress urinary incontinence (SUI) is common in the adult females. Surgical treatment options include synthetic mid-urethral sling (MUS), autologous sling, bulking agents, and Burch colposuspension. The autologous pubovaginal sling (PVS) has re-emerged in response to complications of synthetic MUSs and FDA communications regarding the use of vaginal mesh. This resulted in patients' fear related to vaginal mesh and drop in number of patients seeking surgical treatment of SUI. PVS has re-emerged as an option for treatment of primary SUI. The aim of this review is to familiarize, disseminate information, and share tips for the practicing female pelvic surgeons related to the practice of the autologous fascia sling. Method(s): We reviewed the literature related to the autologous sling. We used the following data bases and search engines: GoPubMed (Transinsight), Cochrane reviews (Wiley Interscience), google scholar (google), and Scopus (Elsevier). Because it is the most commonly investigated and utilized, we focused on the autologous rectus fascia sling. We also focused on the retropubic sling approach because the literature on transobturator rectus fascia sling is sparse. Result(s): Out of 307 articles related to the subject found, 22 articles were included and the rest were excluded. Conclusion(s): ARFS is a valid primary method of treatment for female SUI. Also, it is used in particular indications such as patients with intrinsic sphincter deficiency (ISD), prior pelvic irradiation, failed and/or complicated synthetic MUS, and violated urethral lumen.Copyright © 2018 Wiley Periodicals, Inc.

Maher Christopher, F., et al. (2020). "Summary: 2017 International Consultation on Incontinence Evidence-Based Surgical Pathway for Pelvic Organ Prolapse." Female Pelvic Medicine & Reconstructive Surgery 26(1): 30-36.
	Objective: The aim of this article is to summarize the relevant findings that inform the 2017 International Consultation on Incontinence pathway for surgical treatment of pelvic organ prolapse (POP).; Methods: We conducted an evidence-based review of the English-language peer-reviewed literature relating to POP surgery published prior to December 2016. Level 1 evidence (randomized controlled trials [RCTs] or systematic reviews of RCTs) was preferred; however, level 2 (poor-quality RCT, prospective cohort studies) or 3 evidence (case series or retrospective studies) has been included if level 1 data were lacking. The committee evaluated the literature and made recommendations based on the Oxford grading system summarized as follows: grade A recommendation usually depends on consistent level 1 evidence; grade B recommendation usually depends on consistent level 2 and/or 3 studies, or "majority evidence" from RCTs; grade C recommendation usually depends on level 3 studies or "majority evidence" from level 2/3 studies or Delphi-processed expert opinion; grade D, "no recommendation possible," would be used where the evidence is inadequate or conflicting.; Results: The recommendations from each chapter of the review are presented and serve to inform an evidence-based pathway for the surgical treatment of prolapse. A Web-based interactive application of the pathway is presented.; Conclusions: The 2017 International Consultation on Incontinence pathway on surgery for POP is designed as an adjunct to transparent consultation and consent relating to POP surgery. The final decision regarding surgical intervention can be made only after a shared decision-making process between the patient and the clinician that will evaluate a variety of individual factors that cannot be assessed in the pathway.

Maheshwari, A., et al. (2022). "Elective freezing of embryos versus fresh embryo transfer in IVF: a multicentre randomized controlled trial in the UK (E-Freeze)." Human reproduction (Oxford, England) 37(3): 476-487.
	Study Question: Does a policy of elective freezing of embryos, followed by frozen embryo transfer result in a higher healthy baby rate, after first embryo transfer, when compared with the current policy of transferring fresh embryos?; Summary Answer: This study, although limited by sample size, provides no evidence to support the adoption of a routine policy of elective freeze in preference to fresh embryo transfer in order to improve IVF effectiveness in obtaining a healthy baby.; What Is Known Already: The policy of freezing all embryos followed by frozen embryo transfer is associated with a higher live birth rate for high responders but a similar/lower live birth after first embryo transfer and cumulative live birth rate for normal responders. Frozen embryo transfer is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS), preterm delivery and low birthweight babies but a higher risk of large babies and pre-eclampsia. There is also uncertainty about long-term outcomes, hence shifting to a policy of elective freezing for all remains controversial given the delay in treatment and extra costs involved in freezing all embryos.; Study Design, Size, Duration: A pragmatic two-arm parallel randomized controlled trial (E-Freeze) was conducted across 18 clinics in the UK from 2016 to 2019. A total of 619 couples were randomized (309 to elective freeze/310 to fresh). The primary outcome was a healthy baby after first embryo transfer (term, singleton live birth with appropriate weight for gestation); secondary outcomes included OHSS, live birth, clinical pregnancy, pregnancy complications and cost-effectiveness.; Participants/materials, Setting, Methods: Couples undergoing their first, second or third cycle of IVF/ICSI treatment, with at least three good quality embryos on Day 3 where the female partner was ≥18 and <42 years of age were eligible. Those using donor gametes, undergoing preimplantation genetic testing or planning to freeze all their embryos were excluded. IVF/ICSI treatment was carried out according to local protocols. Women were followed up for pregnancy outcome after first embryo transfer following randomization.; Main Results and the Role of Chance: Of the 619 couples randomized, 307 and 309 couples in the elective freeze and fresh transfer arms, respectively, were included in the primary analysis. There was no evidence of a statistically significant difference in outcomes in the elective freeze group compared to the fresh embryo transfer group: healthy baby rate {20.3% (62/307) versus 24.4% (75/309); risk ratio (RR), 95% CI: 0.84, 0.62 to 1.15}; OHSS (3.6% versus 8.1%; RR, 99% CI: 0.44, 0.15 to 1.30); live birth rate (28.3% versus 34.3%; RR, 99% CI 0.83, 0.65 to 1.06); and miscarriage (14.3% versus 12.9%; RR, 99% CI: 1.09, 0.72 to 1.66). Adherence to allocation was poor in the elective freeze group. The elective freeze approach was more costly and was unlikely to be cost-effective in a UK National Health Service context.; Limitations, Reasons for Caution: We have only reported on first embryo transfer after randomization; data on the cumulative live birth rate requires further follow-up. Planned target sample size was not obtained and the non-adherence to allocation rate was high among couples in the elective freeze arm owing to patient preference for fresh embryo transfer, but an analysis which took non-adherence into account showed similar results.; Wider Implications of the Findings: Results from the E-Freeze trial do not lend support to the policy of electively freezing all for everyone, taking both efficacy, safety and costs considerations into account. This method should only be adopted if there is a definite clinical indication.; Study Funding/competing Interest(s): NIHR Health Technology Assessment programme (13/115/82). This research was funded by the National Institute for Health Research (NIHR) (NIHR unique award identifier) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not nece sarily those of the NIHR or the UK Department of Health and Social Care. J.L.B., C.C., E.J., P.H., J.J.K., L.L. and G.S. report receipt of funding from NIHR, during the conduct of the study. J.L.B., E.J., P.H., K.S. and L.L. report receipt of funding from NIHR, during the conduct of the study and outside the submitted work. A.M. reports grants from NIHR personal fees from Merck Serono, personal fees for lectures from Merck Serono, Ferring and Cooks outside the submitted work; travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. S.B. reports receipt of royalties and licenses from Cambridge University Press, a board membership role for NHS Grampian and other financial or non-financial interests related to his roles as Editor-in-Chief of Human Reproduction Open and Editor and Contributing Author of Reproductive Medicine for the MRCOG, Cambridge University Press. D.B. reports grants from NIHR, during the conduct of the study; grants from European Commission, grants from Diabetes UK, grants from NIHR, grants from ESHRE, grants from MRC, outside the submitted work. Y.C. reports speaker fees from Merck Serono, and advisory board role for Merck Serono and shares in Complete Fertility. P.H. reports membership of the HTA Commissioning Committee. E.J. reports membership of the NHS England and NIHR Partnership Programme, membership of five Data Monitoring Committees (Chair of two), membership of six Trial Steering Committees (Chair of four), membership of the Northern Ireland Clinical Trials Unit Advisory Group and Chair of the board of Oxford Brain Health Clinical Trials Unit. R.M. reports consulting fees from Gedeon Richter, honorarium from Merck, support fees for attendance at educational events and conferences for Merck, Ferring, Bessins and Gedeon Richter, payments for participation on a Merck Safety or Advisory Board, Chair of the British Fertility Society and payments for an advisory role to the Human Fertilisation and Embryology Authority. G.S. reports travel and accommodation fees for attendance at a health economic advisory board from Merck KGaA, Darmstadt, Germany. N.R.-F. reports shares in Nurture Fertility. Other authors' competing interests: none declared.; Trial Registration Number: ISRCTN: 61225414.; Trial Registration Date: 29 December 2015.; Date of First Patient’s Enrolment: 16 February 2016. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Maheshwari, D., et al. (2022). "The Effect of Preoperative Fiber on Postoperative Bowel Function After Pelvic Reconstructive Surgery: A Randomized Controlled Trial." Female Pelvic Medicine & Reconstructive Surgery.
	IMPORTANCE: There are limited studies evaluating the effect of preoperative interventions on postoperative bowel function after prolapse surgery. OBJECTIVE(S): The objective of this study was to evaluate if preoperative fiber intake reduces time to first bowel movement after surgery for pelvic organ prolapse. STUDY DESIGN: We performed a randomized controlled trial of women undergoing pelvic organ prolapse surgery between July 2019 and May 2021. Participants were recruited at their preoperative visit and randomized to receive either 3.4 g psyllium fiber supplementation twice a day for 1 week before surgery or no fiber supplementation before surgery. Postoperative bowel regimen was standardized for both groups. Participants completed a bowel diary for their first postoperative bowel movement after surgery characterized by the Bristol Stool Scale and any associated pain or urgency. The primary outcome was time to first bowel movement. Secondary outcomes included pain associated with first bowel movement. RESULT(S): Eighty-four patients were enrolled in the study. Seventy-one patients had complete data for primary analysis, with 35 patients in the intervention group and 36 patients in the control group. Demographic and perioperative characteristics were similar between the groups. There was no difference found between the groups with respect to time to first bowel movement (control: 68.3 [SD, 25] hours vs intervention: 66.5 [SD, 23] hours, P = 0.749). There was no difference found with pain associated with first bowel movement (visual analog scale median [interquartile range] control: 2.0 [0.0-4.0] vs intervention: 2.0 [1.0-4.0]; P = 0.655). CONCLUSION(S): Preoperative fiber supplementation before prolapse surgery does not improve time to first bowel movement after surgery.Copyright © 2022 American Urogynecologic Society. All rights reserved.

Maheshwari, D., et al. (2022). "The Effect of Preoperative Fiber on Postoperative Bowel Function After Pelvic Reconstructive Surgery: A Randomized Controlled Trial." Urogynecology (Hagerstown, Md.) 28(8): 554-560.
	Importance: There are limited studies evaluating the effect of preoperative interventions on postoperative bowel function after prolapse surgery.; Objective: The objective of this study was to evaluate if preoperative fiber intake reduces time to first bowel movement after surgery for pelvic organ prolapse.; Study Design: We performed a randomized controlled trial of women undergoing pelvic organ prolapse surgery between July 2019 and May 2021. Participants were recruited at their preoperative visit and randomized to receive either 3.4 g psyllium fiber supplementation twice a day for 1 week before surgery or no fiber supplementation before surgery. Postoperative bowel regimen was standardized for both groups. Participants completed a bowel diary for their first postoperative bowel movement after surgery characterized by the Bristol Stool Scale and any associated pain or urgency. The primary outcome was time to first bowel movement. Secondary outcomes included pain associated with first bowel movement.; Results: Eighty-four patients were enrolled in the study. Seventy-one patients had complete data for primary analysis, with 35 patients in the intervention group and 36 patients in the control group. Demographic and perioperative characteristics were similar between the groups. There was no difference found between the groups with respect to time to first bowel movement (control: 68.3 [SD, 25] hours vs intervention: 66.5 [SD, 23] hours, P = 0.749). There was no difference found with pain associated with first bowel movement (visual analog scale median [interquartile range] control: 2.0 [0.0-4.0] vs intervention: 2.0 [1.0-4.0]; P = 0.655).; Conclusions: Preoperative fiber supplementation before prolapse surgery does not improve time to first bowel movement after surgery.; Competing Interests: The authors have declared they have no conflicts of interest. (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Maheshwari, D., et al. (2021). "Effect of Pudendal Blockade on Bladder Emptying After Midurethral Sling: a Randomized Controlled Trial." Female Pelvic Medicine & Reconstructive Surgery 27(2): e465‐e468.
	OBJECTIVES: To evaluate the effect of bilateral pudendal nerve blockade on immediate postoperative bladder emptying after midurethral sling. METHODS: We performed a double‐blinded, randomized, placebo‐controlled trial of women undergoing a midurethral sling procedure between October 2017 and February of 2019. Women older than 18 years were eligible if they were undergoing a midurethral sling with no concomitant procedures and had no preoperative urinary retention. Participant demographics and medical conditions that may affect bladder emptying were recorded preoperatively. Participants were randomized to a bilateral pudendal injection of either bupivacaine or normal saline. After induction of anesthesia, the pudendal injection was administered before any incisions. No other local anesthesia was used. The primary outcome was the rate of passing a standardized void trial. Secondary outcomes included perioperative pain scores, analgesia use, and complications. RESULTS: Ninety‐one participants were enrolled in the study. One patient had a delayed void trial on postoperative day 1, leaving 90 participants for the final analysis. Demographic and perioperative characteristics were similar between the groups. Adjusted logistic regression showed that the administration of a bupivacaine pudendal block led to a higher rate of void trial failure (43% vs 20%, odds ratio = 0.32, P = 0.02 adjusted for age, body mass index, and comorbidities). Postoperative pain scores and analgesia use were similar between the groups. Postoperative complications, including urinary tract infection, mesh erosion, pelvic hematoma, or urinary retention within 6 weeks were similar between the groups. CONCLUSIONS: Our prospective trial demonstrates that a bilateral pudendal blockade before midurethral sling procedure worsens postoperative bladder emptying.

Maheu, C., et al. (2023). "Fear of Cancer Recurrence Therapy (FORT): A Randomized Controlled Trial." Health Psychology 42(3): 182-194.
	Objective: Most fear of cancer recurrence (FCR) interventions have small effects, and few target FCR. This randomized controlled trial (RCT) with breast and gynecological cancer survivors evaluated the efficacy of a cognitive-existential fear of recurrence therapy (FORT) compared to an attention placebo control group (living well with cancer [LWWC]) on FCR. Method(s): One hundred and sixty-four women with clinical levels of FCR and cancer distress were randomly assigned to 6-weekly, 120 min FORT (n= 80) or LWWC (n= 84) group sessions. They completed questionnaires at baseline (T1), posttreatment (T2; primary endpoint), 3 (T3), and 6 months (T4) posttreatment. Generalized linear models were used to compare group differences in the fear of cancer recurrence inventory (FCRI) total score and secondary outcomes. Result(s): FORT participants experienced greater reductions from T1 to T2 on FCRI total with a between-group difference of-9.48 points ( p=.0393), resulting in a medium effect of-0.530, with a maintained effect at T3 ( p=.0330) but not at T4. For the secondary outcomes, improvements were in favor of FORT, including FCRI triggers ( p=.0208), FCRI coping ( p=.0351), cognitive avoidance ( p=.0155), need for reassurance from physicians ( p=.0117), and quality of life (mental health; p=.0147). Conclusion(s): This RCT demonstrated that FORT, compared to an attention placebo control group, resulted in a greater reduction in FCR posttreatment and at 3 months posttreatment in women with breast and gynecological cancer, indicating its potential as a new treatment strategy. We recommend a booster session to sustain gainsCopyright © 2023 American Psychological Association

Mahran, A., et al. (2019). "Sacral neuromodulation treating chronic pelvic pain: a meta-analysis and systematic review of the literature." International Urogynecology Journal 30(7): 1023-1035.
	Introduction and Hypothesis: Sacral neuromodulation (SNM) is gaining popularity as a treatment option for chronic pelvic pain (CPP). Our hypothesis is that SNM is effective in improving CPP.; Methods: A systematic search was conducted through September 2018. Peer-reviewed studies using pre- and postpain intensity scores were selected. The primary outcome was pain improvement on a 10-point visual analog scale (VAS) (adjusted or de novo) in patients with CPP. Secondary outcomes included comparing SNM approaches and etiologies and evaluating lower urinary tract symptoms (LUTS).; Results: Fourteen of 2175 studies, evaluating 210 patients, were eligible for further analysis. The overall VAS pain score improvement was significant [weighted mean difference (WMD) -4.34, 95% confidence interval (CI) = -5.22, to-3.64, p < 0.0001)]. Regarding SNM approach, both standard and caudal approaches had significant reduction in pain scores: WMD -4.32, CI 95% = -5.32, to -3.31 (p < 0.001) for the standard approach, compared with WMD -4.63, 95% CI = -6.57 to -2.69 (P < 0.001), for the caudal approach (p = 0.75). While significant improvement in pain was observed both in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS), the observed improvement was lower in patients with (WMD -4.13, CI 95% -5.36 to -2.90 versus without (WMD -5.72, CI 95% = -6.18, to-5.27) IC/BPS (p = 0.02). SNM was effective in treating voiding symptoms (frequency, urgency, nocturia) associated with IC/BPS (all p < 0.01).; Conclusions: SNM is an effective therapy for CPP in both IC/BSP and non-IC/BSP patients, with better results in non-IC/BSP patients. Outcomes of the antegrade caudal approach were comparable with the standard retrograde approach.

Mai, Z., et al. (2024). "Chinese herbal medicine Er-xian decoction for primary ovarian insufficiency: A systematic review of randomized controlled trials and meta-analyses." European journal of integrative medicine 65: 102333.
	Introduction: The limitations of hormone therapy for managing primary ovarian insufficiency (POI) have prompted trialists to evaluate the Chinese herbal medicine, Er-xian decoction (containing Curculiginis Rhizome, Epimrdii Herba, Angelicae Sinensis Radix, Morindae Officinalis Radix, Phellodendri Chinrnsis Cortex and Anemarrhenae Rhizoma) for treating POI. This review was conducted to evaluate the effectiveness and safety of Er-xian decoction alone or in addition to hormone therapy in treating POI. Method(s): We conducted a systematic review of randomized controlled trials (RCTs) that reported on Er-xian decoction alone or in addition to hormone therapy in women with POI. Seven databases were searched from inception to 7 June 2023. The included studies were screened with Endnote X9, and methodological quality was assessed using the Cochrane "Risk of bias" tool v1.0. Effects were calculated as mean difference (MD), standard mean difference (SMD), or relative risk with 95% confidence interval (CI) using Review Manager 5.4.1, and data not suitable for statistical analyses were assessed by qualitative methods. Result(s): Fifteen studies involving 1274 participants (13 drop-outs) were included. Er-xian decoction plus hormone therapy significantly lowered the follicle-stimulating hormone level (MD -12.48, 95 %CI -15.90 to -9.06; N = 8; P < 0.001) and luteinizing hormone level (MD -8.20, 95 %CI -11.22 to -5.17; N = 8; P < 0.001) and increased the estrogen level (SMD 2.35, 95 %CI 1.52 to 3.18; N = 8; P < 0.001) compared with hormone therapy. There was no significant difference between Er-xian decoction alone and hormone therapy alone in terms of follicle-stimulating hormone level (MD -0.69; 95 %CI, -7.94 to 6.56; N = 5; P = 0.85), luteinizing hormone level (MD 0.29, 95 %CI -3.96 to 4.54; N = 5; P = 0.89) or estrogen level (SMD 0.16, 95 %CI -0.36 to 0.67; N = 5; P = 0.55). In addition, both Er-xian decoction alone and Er-xian decoction plus hormone therapy effectively improved women's menopausal symptoms. Seven studies reported on the occurrence of adverse events, and no severe events were reported. Conclusion(s): The findings suggest Er-xian decoction, with or without hormone therapy, may be an effective treatment for POI. However, limitations in the evidence included a high risk of bias and substantial heterogeneity. Further research should be conducted in well-designed and rigorously executed clinical trials with large samples. Review registration: INPLASY 2,021,110,107.Copyright © 2024 Elsevier GmbH

Maillard, C., et al. (2021). "Diagnosis and Treatment of Vulvo-Perineal Endometriosis: A Systematic Review." Frontiers in surgery 8: 637180.
	Objective: To describe the available knowledge on vulvo-perineal endometriosis including its diagnosis, clinical management and recurrence rate. Methods: We followed the PRISMA guidelines for Systematic Reviews and our study was prospectively registered with PROSPERO (CRD42020202441). The terms " Endometriosis" and " Perineum" or " Vulva" were used as keywords. Cochrane Library, Medline/Pubmed, Embase and Clinicaltrials.gov were searched. Papers in English, Spanish, Portuguese, French or Italian from inception to July 30, 2020 were considered. Reference lists of included articles and other literature source such as Google Scholar were also manually scrutinized in order to identify other relevant studies. Two independent reviewers screened potentially eligible studies according to inclusion criteria. Results: Out of 539 reports, 90 studies were eligible including a total of 283 patients. Their mean age was 32.7 ± 7.6 years. Two hundred sixty-three (95.3%) presenting with vulvo-perineal endometriosis have undergone either episiotomy, perineal trauma or vaginal injury or surgery. Only 13 patients (4.7%) developed vulvo-vaginal endometriosis spontaneously i.e., without any apparent condition favoring it. The reasons that motivated the patients to take medical advice were vulvo-perineal cyclical pain increasing during menstruations (98.2% of the patients, n = 278). Out of the 281 patients for whom a clinical examination was described, 274 patients (97.5%) showed a vulvo-perineal nodule, mass or swelling while six presented with bluish cutaneous lesions (2.1%) and 1 with bilateral polyps of the labia minora (0.4%). All but one patients underwent surgical excision of their lesions but only 88 patients (28.1%) received additional hormonal therapy. The recurrence rate was 10.2% (29 patients) considering a median follow-up period of 10 months (based on 61 studies). Conclusion: In conclusion, vulvo-perineal endometriosis is a rare entity with approximately 300 cases reported in the literature since 1923. With the available knowledge shown in this systematic review, we encourage all practitioners to think about perineal endometriosis in case of perineal cyclical pain with or without previous perineal damage. Diagnosis should be done with clinical exam, perineal ultrasound and pelvic MRI when available. In case of anal sphincter involvement, perianal ultrasound should be performed. Surgical excision of the lesion should be realized in order to remove the lesion and to confirm the diagnosis histologically. Hormonal treatment could be proposed to attempt to decrease the size of a large lesion before surgery or to avoid recurrence of the lesion. As evidence-based approach to the diagnosis, treatment and recurrence rate of affected patients remains a challenge given its low prevalence, the variations in management found in the articles included and the limited quality of available studies, we suggest that a prospective database on vulvo-perineal endometriosis should be generated to increase knowledge but also awareness among healthcare professionals and optimize patients' care. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020202441.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Maillard, Cherif Alami, Squifflet, Luyckx, Jadoul, Thomas and Wyns.)

Mailli, L., et al. (2023). "Uterine artery embolisation: fertility, adenomyosis and size - what is the evidence?" CVIR endovascular 6(1): 8.
	Background: Uterine artery embolisation is well established as a treatment for symptomatic fibroids, however, there remain some uncertainties. We have carried out a focused literature review on three particularly challenging aspects - post-procedure fertility, symptomatic adenomyosis and large volume fibroids and uteri, to enable operators to utilise evidence-based guidance in patient selection, consent, and management.; Review: Literature searches were performed of the PubMed/Medline, Google scholar, EMBASE and Cochrane databases. The outcomes of our analysis of studies which recorded fertility rates in women desiring pregnancy following UAE for symptomatic fibroids found an overall mean pregnancy rate of 39.4%, live birth rate of 69.2% and miscarriage rate of 22%. The major confounding factor was patient age with many studies including women over 40 years who already have lower fertility compared to younger cohorts. Miscarriage rates and pregnancy rates in the studies analysed were comparable to the age matched population. Treatment of pure adenomyosis and adenomyosis with co-existing uterine fibroids with UAE has been shown to produce symptomatic improvement with better outcomes in those with combined disease. Although the effectiveness is not as high as it is in pure fibroid disease, UAE provides a viable and safe alternative for patients seeking symptom relief and uterine preservation. Our analysis of studies assessing the outcomes of UAE in patients with large volume uteri and giant fibroids (> 10 cm) demonstrate no significant difference in major complication rates demonstrating that fibroid size should not be a contraindication to UAE.; Conclusion: Our findings suggest uterine artery embolisation can be offered to women desiring pregnancy with fertility and miscarriage rates comparable to that of the age-matched general population. It is also an effective therapeutic option for symptomatic adenomyosis as well as for the treatment of large fibroids > 10 cm in diameter. Caution is advised in those with uterine volumes greater than 1000cm 3 . It is however clear that the quality of evidence needs to be improved on with an emphasis on well-designed randomised controlled trials addressing all three areas and the consistent use of validated quality of life questionnaires for outcome assessment to enable effective comparison of outcomes in different studies. (© 2023. The Author(s).)

Maimaitiming, N., et al. (2022). "Efficacy and safety of endostar combined with chemoradiotherapy versus chemoradiotherapy alone in locally advanced cervical cancer: A PRISMA-compliant systematic review and meta-analysis." Medicine 101(36): e30170.
	Background: To evaluate the role and safety of endostar in cervical cancer by comparing the efficacy and adverse reactions of endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical carcinoma.; Methods: The quality of the included literature was evaluated by searching the database for the comparison of endostar combined with concurrent radiotherapy and chemotherapy in cervical cancer patients; objective response rate (ORR) and disease control rate (DCR) were used as the main outcome indicators, and statistical analysis was performed using RevMan5.3 and State15.3 software.; Results: A total of 13 studies were included in this study, including 1057 patients with locally advanced cervical cancer, suggesting that endostar combined with chemoradiotherapy can significantly improve the objective response rate (ORR: odds ratio 3.88, 95% confidence interval 2.77-5.45, P < .00001) and disease control rate (DCR: odds ratio 4.43, 95% confidence interval 2.78-7.04; P < .00001), and there was no significant increase in treatment-related adverse reactions.; Conclusions: In this meta-analysis, endostar combined with concurrent chemoradiotherapy significantly improved ORR and DCR in patients with locally advanced cervical cancer without increasing toxicity. However, this study only analyzed the short-term efficacy of endostar, and its influence on overall survival and progression-free survival needs to be further verified in large randomized controlled trials with long-term follow-up.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Maio, M., et al. (2021). "Olaparib plus pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) and/or homologous recombination deficiency (HRD): Initial results of the phase 2 KEYLYNK-007 study." Cancer Research 81(13 SUPPL).
	Background: Poly-ADP-ribose polymerase (PARP) inhibition plus PD-(L)1 blockade has shown encouraging antitumor activity in patients (pts) with recurrent ovarian or breast cancer with BRCAm and in pts with recurrent ovarian cancer regardless of BRCAm or HRD status. We present initial results of the ongoing KEYLYNK-007 (NCT04123366) study of antitumor activity and safety of olaparib + pembrolizumab in pts with previously treated, advanced, HRRm and/or HRD positive solid tumors. Method(s): This phase 2, nonrandomized, multicenter, open-label study enrolled adult pts with histologically/cytologically confirmed, previously treated, advanced solid tumors with centrally-confirmed HRRm and/or HRD positive per Lynparza HRR-HRD assay, and ECOG PS of 0-1, and without prior PARP or PD-(L)1 inhibitor therapy or progression on or <=4 wks after platinum therapy. Pts received olaparib 300 mg BID and pembrolizumab 200 mg Q3W for 35 cycles or until PD, unacceptable AEs, intercurrent illness, or investigator decision. The primary endpoint was ORR. Result(s): As of 25 Sep 2020, 168 pts were enrolled (BRCAm, n = 40; HRRm without BRCAm, n = 64; HRD positive without HRRm, n = 64). Median (range) time from first dose to data cutoff was 4.5 (0.1-8.4), 4.5 (0.1-7.5), and 5.3 (0.3-7.9) mo, respectively. Efficacy outcomes in pts with >=4 mo follow-up are shown in the Table. Grade 3-4 treatment-related AEs occurred in 60 pts (35.7%); 4 pts (2.4%) discontinued treatment due to treatment-related AE; there were no grade 5 treatment-related AEs. Common (>=15%) treatment-related AEs were nausea (39.3%), anemia (30.4%), and fatigue (15.5%), comparable with monotherapy. Conclusion(s): Olaparib + pembrolizumab showed promising antitumor activity with manageable safety in pts with a range of advanced HRRm and/or HRD positive solid tumors, especially BRCAm. Enrollment is ongoing.

Maiorano, B. A., et al. (2021). "Ovarian cancer in the era of immune checkpoint inhibitors: State of the art and future perspectives." Cancers 13(17): 4438.
	Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in OC. Method(s): We searched PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Result(s): 20 studies were identified, of which 16 were phase I or II and 4 phase III trials. These trials used ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, aterolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab). There was no reported improvement in survival, and some trials were terminated early due to toxicity or lack of response. Combining ICIs with chemotherapy, anti-VEGF therapy, or PARP inhibitors improved response rates and survival in spite of a worse safety profile. Conclusion(s): The identification of biomarkers with a predictive role for ICIs' efficacy is mandatory. Moreover, genomic and immune profiling of OC might lead to better treatment options and facilitate the design of tailored trials.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Maiorano Brigida, A., et al. (2022). "Beyond Platinum, ICIs in Metastatic Cervical Cancer: A Systematic Review." Cancers 14(23).
	Background: Cervical cancer (CC) constitutes the fourth most common tumor among the female population. Therapeutic approaches to advanced CC are limited, with dismal results in terms of survival, mainly after progression to platinum-based regimens. Immune checkpoint inhibitors (ICIs) are remodeling the therapeutic scenario of many solid tumors. The role of ICIs in CC should be addressed. Therefore, we systematically reviewed the latest clinical trials employing ICIs in advanced CC to assess which ICIs have been employed and how ICIs might meet the need for new therapeutic options in terms of efficacy and safety.; Methods: The review was conducted following the PRISMA guidelines. The following efficacy outcomes were specifically collected: overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS); for safety: type, number, and grade of adverse events (AEs).; Results: A total of 17 studies were analyzed. Anti-PD1 (pembrolizumab, nivolumab, cemiplimab, balstilimab, and tislelizumab), anti-PD-L1 (atezolizumab), and anti-CTLA-4 (ipilimumab, zalifrelimab) agents were employed both as single agents or combinations. Overall ORR ranged from 0% to 65.9%. ORR ranged from 5.9% to 69.6% in PD-L1-positive patients and from 0% to 50% in PD-L1-negative patients. DCR was 30.6-94.1%. mPFS ranged from 2 to 10.4 months. mOS ranged from 8 months to not reached. PD-L1 status did not impact survival. A total of 33.9% to 100% of patients experienced AEs.; Conclusion: Immunotherapy represents an appealing strategy for patients with advanced CC, as 2 out of 3 patients seem to respond to ICIs. PD-L1 status might be an indicator of response without impacting survival.

Maiorano Brigida, A., et al. (2022). "How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review." Frontiers in Oncology 12: 844801.
	Background: Endometrial cancer (EC) represents the sixth most common female tumor. In the advanced setting, the prognosis is dismal with limited treatment options. Platinum-based chemotherapy represents the actual standard of care in first-line chemotherapy, but no standard second-line chemotherapy is approved, with less than 1/4 of patients responding to second-line chemotherapy. In the last 10 years, immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many solid tumors.; Methods: The review was conducted according to the PRISMA guidelines. We searched EMBASE, MEDLINE, Cochrane Database, and conference abstracts from international societies, up to November 2021. Clinical trials employing ICIs in advanced EC, written in English, were included. Reviews, letters, and commentaries were excluded. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety (number and grade of treatment-related adverse events [TRAEs]) were evaluated.; Results: 15 studies, for a total of 1,627 patients, were included: 14 non-randomized phase I/II trials and 1 randomized phase III trial. Anti-PD1 (pembrolizumab, nivolumab, dostarlimab) and anti-PD-L1 agents (avelumab, atezolizumab, durvalumab) were administered as single agents; pembrolizumab and nivolumab were combined with the tyrosine-kinase inhibitors (TKI) lenvatinib and cabozantinib, respectively; and durvalumab was associated with anti-CTLA4 tremelimumab. 4 studies selected only MSI patients. Single agents determined an ORR from 26.7% to 58% among MSI patients, from 3% to 26.7% among MSS patients. DCR ranged from 53.5% to 88.9% in MSI, 31.4% to 35.2% in MSS patients. The combination of TKI and ICIs determined 32% to 63.6% of ORR in all-comers, 32%-36.2% in MSS patients. 54.2% to 76% of patients developed TRAEs. The combination of ICIs and TKI achieved a higher toxicity rate than single agents (≥G3 TRAEs 88.9%).; Conclusion: ICIs represent an effective option for pretreated advanced EC patients with a tolerable profile. Given the encouraging results in MSI patients, every woman diagnosed with EC should be investigated for MS status. In MSS women, the combination of ICIs and TKI is more effective than monotherapy, notwithstanding safety concerns. PD-L1 cannot predict ICI response, whereas other biomarkers such as MSI and tumor mutational burden seem more accurate. Ongoing randomized trials will further clarify the role of these therapeutic options.; Systematic Review Registration: PROSPERO, CRD42021293538.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Maiorano, Maiorano, Cormio, Maglione, Lorusso and Maiello.)

Majidi, A., et al. (2020). "Common medications and survival in women with ovarian cancer: A systematic review and meta-analysis." Gynecologic Oncology 157(3): 678-685.
	Objectives: Ovarian cancer is usually diagnosed at an advanced stage when five-year relative survival is <50%. Therefore, strategies to improve survival are required. Studies suggest associations between common chronic disease medications such as metformin, statins, beta-blockers, aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) and improved cancer survival. We aimed to review the evidence for a possible relation between these medications and survival among women with ovarian cancer.; Methods: We conducted four systematic reviews and evaluated the risk of bias in the included studies. Where possible, we calculated pooled hazard ratios (pHR) and 95% confidence intervals (CI), excluding studies considered to have the potential for immortal time bias (ITB) which, in practice, was the major source of bias.; Results: We identified 36 studies evaluating one or more of the medications (metformin n = 8, statins n = 12, beta-blockers n = 11, aspirin and/or NA-NSAIDs n = 9). We rated 21 studies as ITB-free. The meta-analysis of the ITB-free studies suggested improved survival in statin users compared to non-users (pHR: 0.76, 95%CI: 0.68-0.85), but no overall survival benefit associated with use of metformin, beta-blockers, aspirin or NA-NSAIDs. The pooled result of two studies did, however, suggest a possible association between perioperative beta-blocker use and improved survival. Studies considered to have potential ITB were more likely to report survival benefits associated with these medications.; Conclusion: Statin use is associated with better ovarian cancer survival but further study, preferably a clinical trial, is required. There are insufficient data to draw conclusions regarding metformin, beta-blockers, aspirin and NA-NSAIDs.; Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Malaga University, o., et al. (2022). Laser Therapy for Treatment of Genitourinary Syndrome of Menopause (GSM) in Postmenopausal Women.
	No Results Available Other: Intervention group|Other: Control Group Change from Baseline in Vaginal pH|Change from Baseline in the deep musculature with the PERFECT protocol|Analysis of the impact on QoL (Quality of life) with the FSFI (Female Sexual Function Index) questionnaire.|Analysis of the impact on QoL (Quality of life) with the SF-12 (Short Form) health questionnaire.|Analysis of the impact on QoL (Quality of life) with Cervantes Scale|Assessment of pain with the CPPQ-Mohedo (Chronic Pelvic Pain Floor) questionnaire|Evaluation of the impact of pelvic floor dysfunction symptoms with the PFDI-20 (Pelvic Floor Distress Inventory) questionnaire|Assesment of menopausal symptoms with the Menopause Rating Scale (MSR). Female Not Applicable 189 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment UMA _SGM_2022 December 15, 2022

Malanowska-Jarema, E., et al. (2023). "A comparative study in learning curves of laparoscopic lateral suspension vs. laparoscopic sacrocolpopexy: preliminary results." Frontiers in surgery 10: 1274178.
	Background: Determination of the learning curve of new techniques is essential to improve safety and efficiency. Limited information is available regarding learning curves of different techniques in laparoscopic pelvic floor surgery.; Objective: The aim of this study was to compare the learning curve of two operative techniques, laparoscopic lateral suspension (LLS) and laparoscopic sacrocolpopexy (LSC).; Material and Methods: We conducted a prospective study to assess the learning curve of LLS and LSC by implementing a structured urogynecologic surgical training program with the use of pelvic trainers for our urogynecology fellow. The fellow was an experienced urogynecologic surgeon, but was laparoscopic suturing and dissection naive at the beginning of the study. She was required to assist in 20 laparoscopic urogynecologic surgeries and undertake laparoscopic suturing and knot tying training with mesh positioning on a laparoscopic trainer for 4 h/week during the trial period. After the completion of this structured training program, the fellow performed LLS and LSC under the supervision of an experienced subspecialist as the primary surgeon. Linear regression analysis was used to compare the data of LLS and LSC learning curves. Subjective pre- and post-operative evaluation of pelvic organ prolapse (POP) and pelvic floor disorders was undertaken preoperatively and 12 months postoperatively using the PFDI-20-Quality of Life validated questionnaire. Follow-up was scheduled 12 months after the surgery and performed by a skilled urogynecologist. Objective cure was defined as Pelvic Organ Prolapse-Qualification (POP-Q) stage <II in any compartment.; Results: The mean operative times of laparoscopic sacrocolpopexy and lateral suspension were 168.26 and 160.33 min, respectively. According to linear regression analysis after 43 procedures, the learning curve for laparoscopic lateral suspension was shorter than for laparoscopic sacrocolpopexy (OPTime 134.69 min). In both groups, there was a significant reduction in bothersome POP symptoms ( p ≤ 0.005). Bladder injuries in two cases and lumbar pain in one case were recorded during the study. Overall objective success at 12 months was 90.7% for LSC and 89.1% for LLS.; Conclusion: Laparoscopic lateral suspension could be an alternative to laparoscopic sacrocolpopexy in the treatment of POP with its good objective and subjective outcomes. Lateral suspension has a shorter learning curve, and it is technically less demanding than LSC. Procedure-dedicated training can accelerate the move from a novice to a master laparoscopic surgeon.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Malanowska-Jarema, Osnytska, Starczewski, Balzarro and Rubilotta.)

Maleki, V., et al. (2021). "Mechanistic and therapeutic insight into the effects of cinnamon in polycystic ovary syndrome: a systematic review." Journal of Ovarian Research 14(1): 130.
	Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in the women at their reproductive age. Nowadays, the use of herbal compounds for lesser side effects, as compared to drug treatments, has become popular for the prevention and reduction of the complications of this disease. Evidence suggests that cinnamon, given its antioxidant and anti-inflammatory properties, can be associated with reduced metabolic complications from chronic non-communicable diseases. This systematic review aimed to determine the potential effect of cinnamon on the metabolic status in the PCOS. PICO framework for current systematic review was Population (P): subjects with PCOS; Intervention (I): oral cinnamon supplement; Comparison (C): the group as control or administered placebo; and Outcome (O): changed inflammatory, oxidative stress, lipid profile, glycemic, hormonal and anthropometric parameters and ovarian function. PubMed, Scopus, EMBASE, ProQuest and Google Scholar were searched from their very inception until January, 2020, considering specific keywords to explore the related studies. Out of 266 studies retrieved by the search strategy, only nine were eligible for evaluation. All clinical trials, animal studies, and published English-language journal studies were eligible for this review. The results showed that increased high-density lipoprotein and insulin sensitivity were increased by the cinnamon supplementation while low-density lipoprotein, triglyceride, and blood glucose were decreased in patients with PCOS. However, the results related to the potential effects of cinnamon on body weight and body mass index were inconsistent, thus calling for further studies. Also, despite improved results regarding the effect of cinnamon on oxidative stress and ovarian function, further studies are required to explore the precise mechanisms. Overall, the effects of cinnamon on the improvement of metabolic status in PCOS were promising. However, to observe clinical changes following cinnamon supplementation in PCOS, more clinical trials with higher doses of cinnamon and a longer duration of intervention are needed. (© 2021. The Author(s).)

Maleki, V., et al. (2019). "Potential roles of carnitine in patients with polycystic ovary syndrome: a systematic review." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 35(6): 463-469.
	Polycystic ovary syndrome (PCOS) is recognized as the most prevalent endocrinopathy in reproductive-aged women. This systematic review was performed with focus on the current knowledge on carnitine concerning metabolic variables in PCOS. PubMed, Scopus, Embase, ClinicalTrials.gov and Google Scholar databases were searched from inception until May 2018. All clinical trials and observational studies published in English-language journals were eligible. Studies that provided insufficient outcomes, animal and in vitro studies were excluded. Out of 451 articles identified in our search, only six articles were eligible for analysis. Two observational studies evaluated the association of serum carnitine levels with metabolic variables, and four clinical trials examined the effect of carnitine supplementation in patients with PCOS. Serum carnitine levels had inverse relationship with glycemic status, body mass index (BMI) and waist circumference. Also, carnitine supplementation resulted in improved weight loss, glycemic status, oxidative stress, follicles and size of ovarian cells; no significant effects were reported on sex hormones and lipid profile. According to the current evidence, carnitine might improve weight loss, glycemic status and oxidative stress. However, to explore the exact mechanisms of carnitine role in patients with PCOS, further studies are recommended.

Maleki, V., et al. (2021). "A comprehensive insight into effects of green tea extract in polycystic ovary syndrome: a systematic review." Reproductive biology and endocrinology : RB&E 19(1): 147.
	Background: Polycystic ovary syndrome (PCOS), as the most common endocrine disorder in reproductive-aged women, is characterized by oxidative stress and ovarian tissue inflammation. Green tea extract (GTE) potentially possesses therapeutic effects for PCOS because of the antioxidant and anti-inflammatory compounds. This systematic review evaluates the potential roles of GTE on metabolic variables, hormone levels, and ovarian function in PCOS.; Methods: A systematic review was conducted of published studies reporting the effects of GTE on PCOS. Several major databases, including PubMed, SCOPUS, and Google Scholar, were searched up from inception to April 2021. Clinical trials and animal studies that assessed the effects of GTE on PCOS were eligible for inclusion.; Results: Of 314 articles found in the search, four human studies and four animal studies were included. All studies in humans showed the effects of GTE on weight loss. GTE's effect on decreasing testosterone levels in humans and LH levels in animals were also reported. In addition, increases in FSH and progesterone levels in animal models were observed. Although GTE improved fasting blood sugar and insulin levels, the effect of GTE on inflammatory parameters, such as TNF-alpha and IL-6 and antioxidant status, was limited to animal studies.; Conclusion: Therefore, this review suggests that GTE could be considered a potential agent to attenuate PCOS complications mainly due to its effect on weight loss and glycemic levels. However, more studies are needed to formulate conclusions about the effects and mechanisms of GTE in PCOS. (© 2021. The Author(s).)

Maleki-Hajiagha, A., et al. (2020). "Intrauterine infusion of autologous platelet-rich plasma in women undergoing assisted reproduction: A systematic review and meta-analysis." Journal of Reproductive Immunology 137: 103078.
	Prior studies have provided conflicting results regarding the use of platelet-rich plasma (PRP) in women undergoing in-vitro fertilization (IVF) or intracytoplasmic injection (ICSI). The objective of this study was to evaluate the effect of the intrauterine infusion of PRP on the outcome of embryo transfer (ET) in women undergoing IVF/ICSI. We searched databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials (CENTRAL). Meta-analysis using a random-effects model was performed to calculate the pooled estimates. Seven studies involving 625 patients (311 cases and 314 controls) were included. The probability of chemical pregnancy (n = 3, risk ratio (RR): 1.79, 95 % confidence intervals (CI): 1.29, 2.50; P < 0.001, I 2 = 0 %), clinical pregnancy (n = 7, RR: 1.79, 95 % CI: 1.37, 2.32; P < 0.001, I 2 = 16 %), and implantation rate (n = 3, RR: 1.97, 95 % CI: 1.40, 2.79; P < 0.001, I 2 = 0 %) was significantly higher in women who received PRP compared with control. There was no difference between women who received PRP compared with control group regarding miscarriage (RR: 0.72, 95 % CI: 0.27, 1.93; P = 0.51, I 2 = 0 %). Following the intervention, endometrial thickness increased in women who received PRP compared to control group (SMD: 1.79, 95 % CI: 1.13, 2.44; P < 0.001, I 2 = 64 %). The findings of this systematic review suggest that PRP is an alternative treatment strategy in patients with thin endometrium and recurrent implantation failure (RIF). Further prospective, large, and high quality randomized controlled trials (RCTs) are needed to identify the subpopulation that would most benefit from PRP.; Competing Interests: Declaration of Competing Interest None declared. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Malik, N. and B. Sahu (2024). "Counselling and management of women with genetic predisposition to gynaecological cancers." European Journal of Obstetrics and Gynecology and Reproductive Biology 294: 44-48.
	Objective: To review the literature with reference to counselling and management of women with genetic predisposition to gynaecological cancers. Method(s): Histochemical analysis, ultrasound, blood investigations, genetic testing, screening and risk-reducing surgery (RRS) are important tools for the management of gynaecological cancers and mortality reduction. Counselling can assist in timely management of gynaecological cancers. Systematic reviews, review articles, observational studies and clinical trials on PubMed, published in the English language, were included in this review. Result(s): The management of women with genetic predisposition to gynaecological cancers through screening tests and RRS has led to a significant decrease in the risk of malignancy through RRS in cases with BRCA1 and BRCA2 gene mutations. RRS and screening have also been found to reduce the mortality rate and increase the survival rate in women with BRCA1 and BRCA2 gene mutations. The efficacy of endometrial cancer surveillance in women with Lynch syndrome is still unproven. RRS has not been reported to be effective in women with Cowden syndrome. The risk of ovarian malignancies in individuals with germline mutations remains minimal in the general population in comparison with genetic mutations. Conclusion(s): Genetic testing and RRS should be implemented in addition to genetic counselling for proper management and mortality reduction of women predisposed to gynaecological cancers.Copyright © 2023 Elsevier B.V.

Malik, T. H., et al. (2021). "Pharmacotherapy and neoteric dietary approaches for polycystic ovary syndrome: A systematic review." Turkish Journal of Endocrinology and Metabolism 25(1): 113-122.
	Polycystic ovary syndrome (PCOS) is an ovarian disorder secondary to the dysregulated hypothalamic-pituitary-adrenal axis leading to androgen excess. Numerous studies have doc-umented that insulin resistance is the key pathophysiological element for the development of PCOS. Insulin acts synergis-tically with luteinizing hormone (LH) to increase androgen production in the theca of the follicles. PCOS is the most ma-lignant endocrine disorder affecting females (7%; from adolescence to menopause). PCOS results in multi-organs derangements categorized by raised androgen levels, irregular menses, and infertility with microcysts formation. The manifestation of PCOS can be specified as polycystic ovaries (morphological) and hyperandrogenemia & hyperlipidemia (metabolic derangements). Clinical hallmarks in PCOS are dyslipidemia, impaired glucose tolerance, hyperandrogenism, microcysts in ovaries, menstrual irregularities, anovulation, and obesity. During clinical examination, a woman's identity is markedly threatened due to hirsutism, acne, alopecia, obesity, irregular menses, and infertility symptoms. Diagnosis is based on European Society for Human Reproduction and Em-bryology/The American Society for Reproductive Medicine or Rotterdam consensus criteria. In this article, we present a precise and comprehensible glimpse of updated and efficient patient management via pharmacotherapy and diet therapy with the most practicable type of diets and their positive out-comes. Nutrients (inositol, isoflavonoids, omega-3) and their dose regimens are discussed. A calorie deficit of 500-1,000 kcal based on the patient profile has proven effective in re-vamping biochemical values and weight loss.Copyright © 2021 by Society of Endocrinology and Metabolism of Turkey. Publication and hosting by Turkiye Klinikleri.

Malinauskiene, V., et al. (2023). "Menstrual cycle abnormalities in women with inflammatory bowel disease and effects of biological therapy on gynecological pathology." World Journal of Clinical Cases 11(21): 4989-4995.
	Inflammatory bowel disease (IBD) is a chronic condition that affects young individuals in their reproductive years. It may have long-term implications on their reproductive, sexual, and mental health. IBD has been related to menstrual abnormalities. Furthermore, the administration of biological therapy can also result in gynecological issues in addition to the disease itself. The purpose of this review was to present potential menstrual cycle problems in patients with IBD, as well as the impact of adalimumab and other anti-tumor necrosis factor medications on gynecological pathology.Copyright © The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Mamajonov, K. I., et al. (2020). "The value of cytoreductive surgery for isolated lymph node recurrence of ovarian cancer." Siberian Journal of Oncology 19(3): 164-171.
	The purpose of the study was to undertake a systematic literature review regarding the role of cytoreductive surgery in treatment of recurrent ovarian cancer, as well as to summarize available data on various current studies and estimate indications for secondary cytoreduction in recurrent ovarian cancer with isolated lymph node involvement. Material and Methods. The search for relevant sources was carried out in PubMed, Gynecol Oncol, Medline, NCCN, Elibrary systems; publications were included from January 2006 up to March 2019. Of the 87 studies found, 26 were used to write a systematic review. Results. Ovarian cancer (OC) remains the leading cause of death from gynecological cancer. The initial treatment for IC-IV stages of OC includes surgical cytoreduction followed by platinum-containing chemotherapy. The best outcomes are observed in patients, in whom complete cytoreduction has been achieved. Despite this fact, most patients develop relapses and the 5-year survival rate is about 30 %. The frequency of lymph node involvement in patients with recurrent OC is not reliably known; isolated lymph node recurrence is reported to occur in 5-32 % of patients. To date, the problem regarding the extent of lymph node dissection in treatment of OC recurrence is still unsolved. In our paper we review the available data concerning the role of secondary cytoreductive surgery for isolated lymph node recurrence of ovarian cancer. Conclusion. Isolated lymph node recurrence of ovarian cancer may indicate a more favorable prognosis and has a less aggressive pattern of OC relapse. The role of secondary cytoreduction in this context is not fully understood, but this category of patients may be one of the most suitable for surgical treatment of ovarian cancer recurrence.Copyright © 2020, Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved.

Mamat, Y., et al. (2023). "Efficacy and Safety of PD-1/PD-L1 Inhibitor as Single-Agent Immunotherapy in Endometrial Cancer: A Systematic Review and Meta-Analysis." Cancers 15(16).
	The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a crucial role in the immune escape mechanism and growth of cancer cells in endometrial cancer (EC). Clinical trials investigating PD-1/PD-L1 inhibitor have shown promising results in other cancers, but their efficacy in EC still remains uncertain. Therefore, this meta-analysis aims to provide an updated and robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis utilized STATA version 17 and RevMan version 5.4 software to pool the results of relevant studies. Five studies conducted between 2017 and 2022, comprising a total of 480 EC patients enrolled for PD-1/PD-L1 inhibitor immunotherapy met the inclusion criteria. The pooled proportion of EC patients who achieved ORR through PD-1/PD-L1 inhibitor treatment was 26.0% (95% CI: 16.0-36.0%; p < 0.05). Subgroup analysis based on mismatch repair (MMR) status showed an ORR of 44.0% (95% CI: 38.0-50.0%; p = 0.32) for the deficient mismatch repair (dMMR) group and 8.0% (95% CI: 0.0-16.0%; p = 0.07) for the proficient mismatch repair (pMMR) group. Pooled proportion analysis by DCR demonstrated an odds ratio (OR) of 41.0% (95% CI: 36.0-46.0%, p = 0.83) for patients undergoing PD-1/PD-L1 inhibitor treatment. Subgroup analysis based on MMR status revealed DCR of 54.0% (95% CI: 47.0-62.0%; p = 0.83) for the dMMR group, and 31.0% (95% CI: 25.0-39.0%; p = 0.14) for the pMMR group. The efficacy of PD-1/PD-L1 inhibitors was significantly higher in the dMMR group compared to the pMMR group, in terms of both ORR (OR = 6.30; 95% CI = 3.60-11.03; p < 0.05) and DCR (OR = 2.57; 95% CI = 1.66-3.99; p < 0.05). In terms of safety issues, the pooled proportion of patients experiencing at least one adverse event was 69.0% (95% CI: 65.0-73.0%; p > 0.05), with grade three or higher AEs occurring in 16.0% of cases (95% CI: 12.0-19.0%; p > 0.05). Based on the subgroup analysis of MMR status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy among dMMR patients. These findings suggest that patients with dMMR status may be more suitable for this treatment approach. However, further research on PD-1/PD-L1 inhibitor immunotherapy strategies is needed to fully explore their potential and improve treatment outcomes in EC.

Mamta, M., et al. (2021). "Hysterectomy outcomes of large uteri – a systematic review."
	
Man, J. K. Y., et al. (2023). "Should IUI replace IVF as first-line treatment for unexplained infertility? A literature review." BMC Women's Health 23(1): 557.
	Background: Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results. Aim(s): This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines. Method(s): The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected. Discussion/conclusion: This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women < 38 years, with good prognosis, and IVF could be offered first to those > 38 years. Patients should be appropriately counselled to enable informed decision making.Copyright © 2023, The Author(s).

Manchanda, R., et al. (2023). "Management of thin endometrium by hysteroscopic instillation of platelet rich plasma: a narrative review." Italian Journal of Gynaecology and Obstetrics 35(1): 81-85.
	Objective. One of the prerequisites for successful pregnancy outcome is the endometrial thickness. In subfertile patients undergoing IVF treatment, the minimum endometrial thickness is presumed to be approximately 7 mm or more prior to embryo transfer. For the treatment of a refractory endometrium, instillation of platelet rich plasma in the subendometrial region via hysteroscopy is a newer technique. This study is conducted to evaluate the effectiveness of PRP treatment in cases of thin endometrium. Materials and Methods. Review of various articles on hysteroscopic instillation of platelet rich plasma was undertaken by searching in the data bases like PubMed, Scopus, EMBASE, Web of Science, Science direct, etc. The studies describing platelet rich plasma instillation and its different techniques including efficacy and their role in achieving clinical pregnancy were included in the present study. We searched studies from January 2000 to January 2022. Results. Here, in the previous studies, we saw promising results with hysteroscopic Platelet rich plasma instillation in infertile women. Conclusions. Autologous platelet rich plasma instillation is not associated with any side effects as it is derived from patients own blood. Also, it is cost effective, less invasive, easily available as well as feasible for the specialist.Copyright © 2023, EDRA S.p.A. All rights reserved.

Mancinelli, E., et al. (2023). "Digital Behavioral Activation Interventions During the Perinatal Period: Scoping Review." JMIR pediatrics and parenting 6: e40937.
	BACKGROUND: Pregnancy is a complex period that implies many biopsychosocial changes, and the way women adapt to these changes impacts their well-being and the chances of developing mental health problems. During the perinatal period, women have expressed a preference for support delivered on the web. In this regard, interventions such as behavioral activation (BA), which are brief and structured psychosocial interventions, seem particularly suited to be delivered through digital solutions. OBJECTIVE: This study aimed to map the literature investigating digital BA interventions deployed during the perinatal period. We paid particular attention to the methodological underpinnings of the studies, the potential impact of BA interventions on symptoms other than depression, and the existence of differences occurring when these interventions were administered during pregnancy versus the postpartum period. METHODS: A systematic search compliant with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews) guidelines was conducted considering 5 bibliographic databases; reference lists and key journals were also screened by 2 independent authors following a double-blind approach. RESULTS: A total of 7 studies published between 2013 and 2022 were included. In total, 2 studies were protocols for randomized controlled trials, 5 were empirical studies, and 1 was a qualitative study. All studies focused on the postpartum period, except for 1 that focused on the broader perinatal period. Promising effects on depression symptoms were reported but not on other psychosocial symptoms. Low intervention adherence has emerged, whereas the usability associated with the digital means used to deploy interventions was scarcely addressed; moreover, information on the digital platforms used was poorly reported overall. CONCLUSIONS: Our findings highlight the scarcity and preliminary nature of digital BA interventions deployed during the perinatal period, where the focus seems more on treatment rather than prevention. Moreover, future studies should also consider and address usability and user engagement, given their relevance to intervention efficacy.

Mangione Carol, M., et al. (2022). "Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement." JAMA 328(17): 1740-1746.
	Importance: Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years.; Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause.; Population: Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions.; Evidence Assessment: The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit.; Recommendation: The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).

Mangir, N., et al. (2023). "Duloxetine in the Treatment of Women with Urinary Incontinence: A Systematic Review and Meta-analysis of Efficacy Data from Randomized Controlled Clinical Trials." Journal of Urological Surgery 10(1): 1-8.
	Duloxetine is the only available agent for the medical treatment of stress urinary incontinence (SUI). In this systematic review, we analyzed the efficacy and safety of duloxetine treatment in women with SUI and stress-predominant mixed urinary incontinence (SPMUI). We searched the literature using OVID MEDLINE, Embase and ULAKBIM (Turkish database) databases for placebo-controlled studies on the use of duloxetine in women with SUI or SPMUI. Data on change in incontinence episode frequency (IEF), decrease in the number of continence pads used, increase in voiding interval (minute) and discontinuation rates due to adverse effects and lack of efficacy (%) were extracted. A total of 12 randomized controlled trials were included. Duloxetine treatment results in an 18% decrease in IEF and 16% decrease in the number of incontinence pads used compared to pre-treatment status. It also increases the time interval between the voids by 18 min. Duloxetine treatment was associated with higher treatment discontinuation rates compared with placebo. The reason for discontinuation was related to the side effects of the treatment rather than lack of efficacy. Duloxetine can be an effective treatment option in women with UI based on high-level evidence supporting its efficacy. Further studies with larger patient populations and longer durations of follow-up are required to assess its safety profile.© Copyright 2023 by the Association of Urological Surgery / Journal of Urological Surgery published by Galenos Publishing House.

Mangla, M., et al. (2022). "Partial mole with coexistent live fetus: A systematic review of case reports." Journal of the Turkish-German Gynecological Association 23(2): 83-94.
	Objective: Molar pregnancy coexistent with a live fetus can be a diagnostic and therapeutic challenge. With increasing incidence of multiple pregnancies, there has also been an increase in twin pregnancy with one mole in the recent years. The authors discuss the epidemiology, clinical presentation, and prenatal diagnosis and attempt to design a possible management strategy, to help guide the treating physician, in the management of partial mole with live pregnancy, thereby improving maternal and fetal prognosis. Material(s) and Method(s): Numerous case reports have been published in various journals regarding management of individual cases of partial molar pregnancy coexistent with live fetus (PMCF). Therefore, we conducted a systematic review of all the case reports and short case series in English concerning partial mole with live pregnancy from 1999 to 2019, that is in the last 20 years. Result(s): In total, 44 case reports of PMCF were analyzed. The mean gestational age at diagnosis was 20+6 (range: 10-40) weeks. Less than half (19/44; 43.2%) were asymptomatic at the time of detection and PMCF was detected on routine scan done for fetal well-being or 11-13-week scan. The majority (56.8%) resulted in the birth of a healthy live fetus. Gestational trophoblastic neoplasia developed in 3/44 (6.8%). Conclusion(s): PMCF involves a high risk of bleeding, preterm labour, intrauterine growth restriction and stillbirth. Successful management of such cases needs prenatal diagnosis, antepartum surveillance and post-natal follow-up. An obstetrician, maternal fetal medicine specialist, gynecology oncologist and neonatal intensivist should be involved in the care of such pregnancies.© Copyright 2022 by the Turkish-German Gynecological Education and Research Foundation

Manitoba University, o. (2021). Evaluating Overcoming Anxiety in Pregnancy and Postpartum as an Online Self-Directed Program.
	No Results Available Behavioral: Overcoming Anxiety in Pregnancy and Postpartum Online Self-Directed Program Change in Perinatal Anxiety Symptoms from Baseline|Change in Perinatal Depression Symptoms from Baseline|Change in COVID-19 Stress from Baseline|Change in Non-Specific Psychological Distress from Baseline|Change in Life Stress from Baseline|Change in Maternal Antenatal Attachment from Baseline|Change in Maternal Postnatal Attachment from Baseline|Change in Maternal Efficacy from Baseline|Acceptability of the Online Self-Directed Program|Participant Satisfaction with the Online Self-Directed Program|Participant Experiences in the Online Self-Directed Program Female Not Applicable 95 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment P2020:104|53294 June 29, 2022

Manodoro, S., et al. (2022). "Stem Cells in Clinical Trials for Pelvic Floor Disorders: a Systematic Literature Review." Reproductive sciences (Thousand Oaks, Calif.) 29(6): 1710-1720.
	Pelvic floor disorders (PFDs) include a series of conditions that can be poorly tolerated, negatively affecting the quality of life. Current treatment options show unsatisfactory results and new ones are therefore needed. Stem cell (SC) therapy might be an alternative treatment strategy. This systematic review aims to define the state of art of SC therapy for PFDs in clinical trials, by systematically reviewing the available evidence. A systematic search strategy was conducted up to November 7, 2020, in PubMed, Scopus, Cochrane Library, and ISI Web of Science. Preclinical studies on animal models were not considered. Studies were included when the patients were affected by any PFDs and cells were isolated, cultured, and characterized as SC. The study protocol was registered in PROSPERO (CRD42020216551). A total of 11 prospective clinical studies were included in the final assessment, specifically 7 single-arm studies dealing with SC therapy for stress urinary incontinence and 4 with anal incontinence. Among the latter, there were two prospective, single-arm studies and two randomized controlled trials. No papers concerning the use of SC for prolapse repair were retrieved. Due to the great heterogeneity, data pooling was not possible. Stem cell injection resulted in a safe procedure, with few mild adverse side effects, mostly related to harvesting sites. However, a clear beneficial impact of SC treatment for the treatment of pelvic floor disorders could not be demonstrated. Further larger targeted studies with control arms are needed before any conclusions can be made. (© 2021. The Author(s).)

Manojlović, M., et al. (2021). "Effects of Combined Resistance and Aerobic Training on Arterial Stiffness in Postmenopausal Women: A Systematic Review." International Journal of Environmental Research and Public Health 18(18).
	The aim of this systematic review was to investigate the effects of combined resistance and aerobic exercise on arterial stiffness in postmenopausal women. Two databases, PubMed and Google Scholar were searched to identify relevant studies. The methodological quality was assessed with the Physiotherapy Evidence Database (PEDro) scale. Only seven studies met the eligibility criteria, and their outcomes were presented. Four studies demonstrated the effects of combined resistance and aerobic training, while three showed the effectiveness of exercise with both training components, aerobic and resistance. In all studies, arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV). Participants were middle-aged or older postmenopausal women of various health statuses (hypertensive, with comorbidities or healthy). The results unequivocally show that combined training reduces arterial stiffness. The most important finding of this review paper is that the applied type of exercise decreased baPWV in the range of 0.6-2.1 m/s. Moreover, combined resistance and aerobic exercise for 12 weeks, performed three times a week for about 60 min per training session, at a moderate intensity (40-60% HRR or HRmax), may be clinically meaningful to the cardiovascular system. In conclusion, we can say that combined resistance and aerobic training, or exercise with resistance and aerobic components, have important health implications for the prevention of cardiovascular disease and the maintenance or improvement of health in middle-aged and older postmenopausal women with different health conditions.

Manouchehri, A., et al. (2023). "Polycystic ovaries and herbal remedies: A systematic review." JBRA Assisted Reproduction 27(1): 85-91.
	Objective: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects one in every 15 women worldwide. This disorder is mainly characterized by increased levels of male hormones (androgens), acne, and hirsutism, and can lead to long-term insulin resistance, miscarriage, or even infertility in women. PCOS is a disorder that can be treated with natural and allopathic remedies that work against the PCOS mechanism. The present study reviews previous studies on the treatment of PCOS using natural drugs.; Methods: The data in this study were collected from articles published in reputable databases including ScienceDirect, PubMed, Google Scholar, and SID in the field of medicinal plants from 1990 to 2021.; Results: A review of the literature showed that plants such as aloe vera and chamomile improve fertility by increasing the number of ovarian follicles. Besides, Vitex agnus-castus and octane reduce hirsutism by reducing testosterone and androgen levels. It was also shown that liquorice, ginseng, cinnamon, and de chiro Inositol improve the adverse effects of diabetes caused by PCOS by lowering lipid and blood glucose levels. Moreover, Stachys lavandulifolia and fennel are effective in changing endometrial tissue parameters in PCOS by reducing estrogen and hyperplasia.; Conclusions: Various studies have shown that herbal medicines can improve PCOS symptoms in women with minimal side effects but a longer treatment cycle.

Mansouri, A., et al. (2021). "Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol." BMJ Open 11(1): e041463.
	Introduction: Patients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months.; Methods and Analysis: ETHICS AND DISSEMINATION: This study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150.; Trial Registration Number: ISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mansouri, K., et al. (2020). "Clinical effects of curcumin in enhancing cancer therapy: A systematic review." BMC Cancer 20(1): 791.
	Background: Curcumin is herbal compound that has been shown to have anti-cancer effects in pre-clinical and clinical studies. The anti-cancer effects of curcumin include inhibiting the carcinogenesis, inhibiting angiogenesis, and inhibiting tumour growth. This study aims to determine the Clinical effects of curcumin in different types of cancers using systematic review approach. Method(s): A systematic review methodology is adopted for undertaking detailed analysis of the effects of curcumin in cancer therapy. The results presented in this paper is an outcome of extracting the findings of the studies selected from the articles published in international databases including SID, MagIran, IranMedex, IranDoc, Google Scholar, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant publications were selected based on the plausible keywords, in accordance with the study aims, as follows: prevalence, curcumin, clinical features, cancer. Result(s): The results are derived based on several clinical studies on curcumin consumption with chemotherapy drugs, highlighting that curcumin increases the effectiveness of chemotherapy and radiotherapy which results in improving patient's survival time, and increasing the expression of anti-metastatic proteins along with reducing their side effects. Conclusion(s): The comprehensive systematic review presented in this paper confirms that curcumin reduces the side effects of chemotherapy or radiotherapy, resulting in improving patients' quality of life. A number of studies reported that, curcumin has increased patient survival time and decreased tumor markers' level.Copyright © 2020 The Author(s).

Mantovani, G., et al. (2019). "Reviewing vulvar Paget's disease molecular bases. Looking forward to personalized target therapies: a matter of CHANGE." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	OBJECTIVES: To review the published literature on vulvar Paget's disease (VPD) molecular bases, aiming to support the need for tailored treatment in women affected by this 'orphan' tumor. METHODS: MEDLINE-PubMed and Scopus were interrogated using the following algorithm: (extramammary OR extra mammary OR vulvar) AND (paget OR pagets OR paget's) AND (molecular OR biological OR marker OR protein OR target OR expression). The inclusion criteria for papers were: peer-reviewed English-language journals, articles published in the last 30 years, studies focused on fixed research questions, quality assessment on the basis of the relevance and contribution to the selected topics. RESULTS: A total of 42 studies were selected, providing the following results. Molecular markers implicated in cell cycle transitions seem to be related to prognosis and could help to tailor conventional treatments. Fragmented but consistent preliminary data exist on hormonal receptor expression, ERBB2 amplification/overexpression and abnormal vascular proliferation, offering a concrete possibility for target therapy trials. Conversely, other fields linked to the possible use of immunotherapy are currently relatively unexplored, such as the tumor 'immune contexture', programmed death ligand-1 (PD-L1) expression and defects in the mismatch repair system, which is involved in genomic instability and potentially promotes a consistent response to treatment. CONCLUSIONS: Additional effort is needed to further characterize these aspects. Centralization of patients in dedicated units would be beneficial for concentrating patient numbers, collecting valuable clinical data and conducting clinical trials. Interdisciplinary study platforms should be developed and integrated into wider multicentric networks.

Manzoor, I., et al. (2021). "Applications of High-Intensity Focused Ultrasound in the Treatment of Different Pathologies." Journal of Diagnostic Medical Sonography 37(2): 171-178.
	Objective: The purpose of this literature search was to review the benefits of high-intensity focused ultrasound (HIFU) and its application for different pathologies. Method(s): This review summarizes the implementation of HIFU for different pathologic conditions. An National Center for Biotechnology Information, PubMed, MEDLINE, Medscape, and Google Scholar database search (1992-2016) was done with the following keywords: high-intensity focused ultrasound; uses of HIFU; and applications of HIFU in the liver, bones, uterine fibroids, prostate, breast, thyroid, pancreas, kidneys, brain, urinary bladder, and so on. Tables and graphs were created for all the variables included in the study, and descriptive statistics were applied. Result(s): In total, 110 records were identified, through database search. In addition, 20 articles were identified through other sources. Screening of the articles was performed, and 20 were removed due to duplication; further screening was performed for 110 articles, and 30 records were further excluded. Full-text articles were assessed for eligibility and 30 were retained. Full-text articles were excluded (N = 36) on the basis that research was performed on animals, and this review article was performed solely for human application. There were 42 qualitative syntheses that researches added to the review. In addition, 42 quantitative synthesis (meta-analysis) were added to the review. Conclusion(s): The conclusion of this narrative review indicates that HIFU is noninvasive, nonharmful, and effective in treating diseases and tumors of the brain, breast, bone, hepatic, renal, pancreas, and prostate; uterine fibroids; and many other solid tumors. Recent technological development suggests that HIFU is likely to play a significant role in future surgical practices. Further research works should be conducted on a large sample size to obtain more accurate results in the application of HIFU.Copyright © The Author(s) 2020.

Manzour, N., et al. (2022). "Pattern of relapse in patients with stage IB1 cervical cancer after radical hysterectomy as primary treatment. Minimally invasive surgery vs. open approach. Systematic review and meta-analysis." Gynecologic Oncology 164(2): 455-460.
	Background: After the LACC trial, the SUCCOR study, and other studies, we know that patients who have undergone minimally invasive surgery for cervical cancer have worse outcomes, but today, we do not know if the surgical approach can be a reason to change the pattern of relapses on these patients. We evaluated the relapse pattern in patients with stage IB1 cervical cancer (FIGO, 2009) who underwent radical hysterectomy with different surgical approaches.; Methods: A systematic review of literature was performed in PubMed, Cochrane Library, Clinicaltrials.gov, and Web of science. Inclusion criteria were prospective or retrospective comparative studies of different surgical approaches that described patterns or locations of relapse in patients with stage IB1 cervical cancer. Heterogeneity was assessed by calculating I2.; Results: The research resulted in 782 eligible citations from January 2010 to October 2020. After filtering, nine articles that met all inclusion criteria were analyzed, comprising data from 1663 patients who underwent radical hysterectomy for IB1 cervical cancer, and the incidence of relapse was 10.6%. When we compared the pattern of relapse (local, distant, and both) of each group (open surgery and minimally invasive surgery), we did not see statistically significant differences, (OR 0.963; 95% CI, 0.602-1.541; p = 0.898), (OR 0.788; 95% CI, 0.467-1.330; p = 0.542), and (OR 0.683; 95% CI, 0.331-1.407; p = 0.630), respectively.; Conclusion: There are no differences in patterns of relapse across surgical approaches in patients with stage IB1 cervical cancer undergoing radical hysterectomy as primary treatment.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Maoz, A., et al. (2019). "Emerging serine-threonine kinase inhibitors for treating ovarian cancer." Expert Opinion on Emerging Drugs 24(4): 239-253.
	Introduction: Ovarian cancer is the leading cause of gynecologic cancer death, owing to high rates of incurable, recurrent disease after initial treatment. Serine threonine kinases (STKs) have been proposed as potential therapeutic targets in ovarian cancer because of their role in the initiation and progression of cancers. Experience in non-ovarian cancers suggests that STK inhibitors are active against tumors with specific molecular alterations. Areas covered: This review discusses STK inhibitors in active development in phase II/III clinical trials for ovarian cancer. PubMed and ClinicalTrials.gov were systematically searched to identify STK inhibitor trials for ovarian cancer; active development was confirmed via Pharmaprojects. Available data regarding the efficacy and safety of these compounds are explored. Expert opinion: STK inhibitors currently in development have modest activity as single agents and are unlikely to achieve approval as monotherapy for unselected ovarian cancer patients. Combination trials of STK inhibitors with chemotherapy and/or targeted therapies have suggested an acceptable efficacy/toxicity ratio for certain combinations but confirmatory studies are needed. Carefully designed trials, especially those including somatic molecular analysis, may help identify the subsets of patients most likely to benefit from these therapeutic strategies and determine the role of STK inhibitors in the evolving landscape of precision oncology.Copyright © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Mapanga, W., et al. (2020). "Treatment of pre- And confirmed cervical cancer in HIV-seropositive women from developing countries: A systematic review." Systematic Reviews 9(1): 79.
	Background: Cervical cancer has become a major public health challenge in developing countries with a reported age-standardised incidence rate of about 17.9/100,000/year and lifetime risks approaching 1 in 20 in some settings. Evidence indicates that HIV-seropositive women are 2 to 12 times more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women. There is a lack of rigorous evidence on which treatment methods are being utilised for HIV-positive women, and this review aims to synthesise available evidence on treatment modalities for both cervical neoplasia and cervical cancer in HIV-seropositive women in developing countries. Method(s): A systematic review guided by a published protocol was conducted. Online databases including MEDLINE/PubMed, Embase, CINAHL and Emerald (via EBSCOhost), PsycINFO, Cochrane Library, and health databases, which cover developing countries (3ie Systematic Reviews, WHO library and databases, World Bank website), were searched for published articles. Additional articles were found through citation, reference list tracking, and grey literature. Study design, treatment category, geographic country/region, and key outcomes for each included article were documented and summarised. Result(s): Thirteen research articles from sub-Saharan Africa, Asia, and South America were included. Eight (61.5%) articles focused on the treatment of cervical cancer with the remaining five (38.5%) assessed cervical neoplasia treatment. The available cervical cancer treatments, radiotherapy, chemotherapy, chemoradiation, and surgery are effective for HIV-seropositive patients, and these are the same treatments for HIV-negative patients. Both cryotherapy and LEEP are effective in reducing CIN2+ among HIV-seropositive women, and a choice between the treatments might be based on available resources and expertise. Radiation, chemotherapy, concurrent treatment using radiotherapy and chemotherapy, and surgery have shown the possibility of effectiveness among HIV-seropositive women. Cervical cancer stage, immunosuppressive level including those on HAART, and multisystem toxicities due to treatment are associated with treatment completion, prognostic, and survival outcomes. Conclusion(s): Treatment of cervical cancer is based on the stage of cancer, and poor outcomes in most developing countries might be due to a lack of optimal treatment regimen. Those infected with HIV were younger and had advanced cervical cancer as compared to those who were HIV-negative. Facilitation and putting HIV-infected people on life-long ART is of importance and has been found to have a positive impact on cervical cancer treatment response. Research on precancerous lesions and cervical cancer management of HIV-seropositive patients focusing on the quality of life of those treated; the effectiveness of the treatment method considering CD4+ count and ART is required. Systematic review registration: PROSPERO CRD42018095707Copyright © 2020 The Author(s).

Maqbali, M., et al. (2019). "Exercise Interventions to Manage Fatigue in Women With Gynecologic Cancer: A Systematic Review." Oncology Nursing Forum 46(1): 71-82.
	Problem Identification: Fatigue has a negative impact on the quality of life of patients with cancer. The aim of this review is to evaluate studies on the effectiveness of exercise interventions in reducing fatigue in women with gynecologic cancer.; Literature Search: The review was conducted according to the PRISMA guidelines using the CINAHL®, MEDLINE®, EMBASE, PsycINFO®, and Cochrane Library databases. The Critical Appraisal Skills Programme was used for quality assessment.; Data Evaluation: Five studies met the inclusion criteria.; Synthesis: Evidence suggests that exercise interventions result in significant reductions in fatigue in women with gynecologic cancer. However, the current evidence is limited. Additional studies are required to address the dose-dependent outcomes of exercise interventions on fatigue in women with gynecologic cancer.; Implications for Nursing: Findings support the positive effects of exercise interventions in reducing fatigue in women with gynecologic cancer, suggesting that healthcare professionals may consider including exercise programs into management plans for this population.

Maragianni, O. and K. Gourounti (2021). "Stress and infertility: a review of possible causes and midwifery care." Review of Clinical Pharmacology and Pharmacokinetics, International Edition 35(3): 135-141.
	Chronic stress (when present for an extended period of time) can lead to depression and sleep difficulties. In specific circumstances, excessive stress can affect a woman's hormone levels, delaying or inhibiting ovulation. Furthermore, the couple's sex life may be interrupted in some circumstances. However, high levels of stress can lead to biological, psychological and social problems and even serious harm to humans. Women with infertility report increased levels of anxiety and depression, so it is clear that infertility causes stress. What is less clear, is whether or not stress causes infertility. The present review aims to gather narrative and systematic reviews of stress studies. This review presents literature regarding the effects of stress on human daily life and what is the correlation with infertility. infertility is described as the inability to conceive or give birth to a healthy child. Secondary infertility is described as a circumstance in which the woman has previously been able to conceive and give birth to a healthy offspring [1]. In general, people with ovulation abnormalities have a number of distinct indications and symptoms. When young women complain of absenteeism or irregular menstruation, or when she contact the doctor about their inability to conceive, the issue is generally detected [2-4].Copyright © PHARMAKON-Press.

Marcelissen, T., et al. (2022). "Storage symptoms after surgical treatment of stress urinary incontinence in women: a clinical review." Clinical and Experimental Obstetrics and Gynecology 49(3): 061.
	Objectives: Minimally invasive sling procedures for the treatment of stress urinary incontinence has gained a topic of great interest for the last decades. However, postoperative storage symptoms after sling implantation or conventional surgical techniques are one of the most distressing complications which can significantly impair quality of life. The current review aims to focus on the development of storage symptoms after surgical treatment in comparison of different surgical techniques. Mechanism: A narrative review has been performed to identify literature reporting the incidence of storage symptoms after female stress urinary incontinence surgery. The results of systematic reviews and meta-analysis have been included in this review. Findings in brief: Pubovaginal slings have a higher risk for developing storage symptoms. In contrast, standard midurethral slings (SMUS) and colposuspensions demonstrate comparable rates of postoperative storage symptoms. Regarding SMUS, the surgical route did not demonstrate significant differences in storage symptoms. In comparison between SIMS and SMUS, no significant difference of postoperative storage symptoms could be identified. Conclusion(s): Pubovaginal slings have the highest risk for postoperative storage symptoms in comparison to colposuspension and SMUS and SIMS. Furthermore, surgical technique and misplacement of sling may contribute significantly in the development of postoperative storage symptoms.Copyright: © 2022 The Author(s).

Marcelo, C., et al. (2023). "Use of calcineurin inhibitors in the treatment of reproductive failure: systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Marchand, G., et al. (2021). "Contained and uncontained morcellation in hysterectomy and myomectomy: A systematic review and meta-analysis." Turkish Journal of Obstetrics and Gynecology 18(4): 311-321.
	We sought to analyze all high-quality studies available regarding the possible differences in contained and uncontained techniques for morcellation of fibroids and uteri. We systematically searched PubMed, Cochrane Central, Scopus, ClinicalTrials.Gov, MEDLINE and Web of Science from September 2010 to September 2020 for our search terms. We included studies that specifically enrolled patients undergoing power morcellation myomectomy or power morcellation hysterectomy procedures. In our search, we had no restriction to age, country, or publication date. We extracted data related to study design, baseline characteristics of patients, and perioperative outcomes such as total operative time, total blood loss, and duration of hospital stay. We found no substantial difference in total operative time between contained power morcellation and uncontained manual morcellation myomectomy (p=0.52), but contained power morcellation had a significantly longer total operative time than uncontained power morcellation for hysterectomy and myomectomy [135.50 vs. 93.33 minutes, (p=0.003)]. Total blood loss was comparable for contained power morcellation versus uncontained manual morcellation myomectomy (p=0.32) and contained power morcellation versus uncontained power morcellation myomectomy or hysterectomy (p=0.91). Contained power morcellation and uncontained manual morcellation myomectomy had comparable hospital stay periods (p=0.5). Contained power morcellation leads to a longer operating time than uncontained power morcellation for both hysterectomy and myomectomy. No differences were found in comparisons of blood loss, operative time, or comparison to manual methods of morcellation.

Marchand, G., et al. (2021). "Systematic review and meta-analysis of the efficacy of gabapentin in chronic female pelvic pain without another diagnosis." AJOG Global Reports 2(1): 100042.
	Background: While widely used for the treatment of chronic pelvic pain, limited data exists on efficacy of gabapentin, especially in the subgroup of women suffering from chronic pelvic pain without a known diagnosis, such as endometriosis.; Objective: This study aimed to assess the efficacy of gabapentin when administered to women with chronic pelvic pain without another diagnosis.; Study Design: We performed a Systematic Review and Meta Analysis including all controlled clinical trials addressing the use of gabapentin for the treatment of chronic pelvic pain without another diagnosis. We searched PubMed, Scopus, Web of Science, ClinicalTrials.Gov, MEDLINE, and The Cochrane Library from inception of each database to April 30, 2021. We included all the studies that fulfilled the following criteria: (1) population: women suffering from chronic pelvic pain without another identified diagnosis (such as endometriosis); (2) intervention: gabapentin (regardless of the dosage); (3) comparator:placebo; (4) outcomes: pain score (visual analog scale) after 3 months and pain score (visual analog scale) after 6 months as primary outcomes; and (5) study design: we only included randomized or controlled clinical trials. Our exclusion criteria included (1) uncontrolled clinical trials, (2) studies that did not report data or measures for any of our selected outcomes, (3) studies that included patients with surgically or clinically diagnosed endometriosis, or (4) studies with no full-text manuscript available. Risk of bias assessment was performed using the Cochrane risk of bias tool. We analyzed dichotomous outcomes as percentages and totals, whereas continuous outcomes were analyzed using mean difference, standard deviations, and relative 95% confidence intervals using the inverse variance method.; Results: We included 4 placebo-controlled randomized controlled trials. Analysis was hindered because half of the studies (n=2) used the visual analog scale pain score and the other half (n=2) used the numerical rating scale. The analysis showed that when compared with the placebo, gabapentin significantly lowered the visual analog scale pain score at 3 months (mean difference, 0.79; 1.23 to 0.35; P =.005) and 6 months (mean difference, 1.68; 2.30 to 1.05; P =.001) and the numerical rating scale pain score at 3 months (mean difference, 0.20; 0.25 to 0.15; P =.001). However, in terms of the numerical rating scale pain score after 6 months, the 2 groups showed no significant difference (mean difference, 0.27; 0.80 to 0.26; P =.32).; Conclusion: Gabapentin may hold benefit for the management of chronic pelvic pain, with significant improvement in pain seen in both scales at 3 months when compared with the placebo, but only in the visual analog scale group at 6 months of usage. Secondary to the differences in the nature of the 2 scales, a further weighted combined analysis was not possible. (© 2021 The Authors.)

Marchand, G., et al. (2023). "Systematic review and meta-analysis of robotic radical hysterectomy vs. open radical hysterectomy for early stage cervical cancer." Health Sciences Review 8: 100109.
	Objective: Recent data has brought into question the safety of minimally invasive techniques for radical hysterectomy in the treatment of early stage cervical cancer. After the publication of several new studies, we aimed to compare robotic radical hysterectomy (RRH) with open radical hysterectomy (ORH) in the management of women with early stage cervical cancer, while excluding minimally invasive cases performed without robotic assistance. Data Sources: We searched six databases from inception until 11/30/2021. The original search found 233 unique papers, and ultimately 35 studies, comprising 11,888 total radical hysterectomies, met criteria for our final analysis. We included all studies including the intervention of RRH for early stage cervical cancer, with the comparator of ORH. We included randomized clinical trials (RCTs), case-control, retrospective cohort, and prospective cohort. We included studies that had robotic and laparoscopic arms, but excluded any studies that did not specifically provide specific data as to each group. We analyzed continuous data using mean difference and a 95% confidence interval, while dichotomous data were analyzed using odds ratio and a 95% confidence interval. Result(s): We found that there was no significant difference between RRH and ORH regarding five-year Overall Survival (OR=1.28[0.66,2.46], (P = 0.46)), disease free survival (OR=0.94[0.77,1.14], (P = 0.51)), or recurrence (OR=0.92[0.75,1.13], (P = 0.44)) intraoperative complications (OR=0.75[0.55,1.02], (P = 0.07)), or mortality (OR=0.81[0.53,1.22], (P = 0.31)). We found that RRH was better than ORH in terms of estimated blood loss (MD=-397.95[-471.65,-324.24], (P < 0.001)), blood transfusion rate (OR=0.13[0.10,0.17], (P = 0.001), post-operative complications (OR=0.65[0.46,0.91], (P = 0.01)), and length of hospital stay (MD=-3.99[-4.67,-3.31], (P < 0.001)). While ORH was better than RRH regarding operation time (MD=15.34[2.21,28.47], (P = 0.02)) and number of resected lymph nodes (MD=-2.64[-4.12,-1.15], (P = 0.005)). Conclusion(s): The previously seen increase in cancer recurrence and decrease in survival no longer seem to be present when we consider the newest high-quality data and exclude non-robotic minimally invasive techniques. RRH was associated with less estimated blood loss, a lower transfusion rate, a shorter hospital stay, and fewer postoperative complications. ORH seems to be associated with a higher number of resected lymph nodes, and a shorter operative time. Trial registration details: Prospero Prospective Registration Number: CRD42022306991 Registration link: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=306991Copyright © 2023

Marchand, G., et al. (2022). "Efficacy of laparoscopic and trans-abdominal cerclage (TAC) in patients with cervical insufficiency: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 270: 111-125.
	Background: Cervical insufficiency (CI) may result in preterm delivery. We sought out to perform this review and analysis to compare the efficacy of laparoscopic and open transabdominal cerclage (TAC) in patients suffering with CI.; Methods: Our search included PubMed, Scopus, MEDLINE, ClinicalTrials.Gov, Cochrane and Web of Science. We analyzed the data with Open Meta-Analyst Software as well as Review Manager Software. We included observational and randomized controlled trials that included patients with CI that underwent laparoscopic cerclage or TAC.; Results: We included a total of 43 studies. Laparoscopic and TAC had a positive effect by increasing gestational age (GA); for the laparoscopic group (mean deviation (MD)) = 14.86 weeks (W), 95% CI [10.67, 19.05], P < 0.001) and TAC (MD = 12.79 W, 95% CI [10.97, 14.61], P < 0.001). Furthermore, improvements in all outcomes assessed (total fetal survival rate, neonatal weight, and prevention of delivery at a gestational age of<24 weeks) were all significant with the exception of the prevention of all preterm deliveries<37 weeks; for both laparoscopic at (RR = 0.116, 95% CI [-0.006, 0.238], P = 0.063) and TAC at (MD = 1, 95% CI [0.45, 2.24], P = 1), and for prevention of deliveries<34 weeks for the laparoscopic group (RR = 0.446, 95% CI [-0.323, 1.215], P = 0.256) only.; Conclusions: Although limited data prevented pregnancy and prepregnancy subgroups as well as a head-to-head comparison, we still found that in patients suffering from CI, both TAC and laparoscopic approaches to cerclage revealed a positive effect in preserving the pregnancy. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Marchetti, C., et al. (2020). "Letrozole in the management of advanced ovarian cancer: an old drug as a new targeted therapy." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 30(7): 1058-1064.
	At present, there is no standard of care on the use of letrozole in ovarian cancer management. We performed a systematic review of the available literature addressing this issue. Data demonstrated a role for letrozole in ovarian cancer, in both the primary and recurrent setting. Letrozole, which has a favorable toxicity profile, seems to assure a prolonged recurrence-free interval, particularly when used as maintenance treatment, in low grade serous ovarian cancer; in recurrent cases it had also led to prolonged disease control. However, the optimal setting and biologically relevant patient population needs to be defined in larger trials.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Marchetti, C., et al. (2019). "Role of intraperitoneal chemotherapy in ovarian cancer in the platinum-taxane-based era: A meta-analysis." Critical Reviews in Oncology/Hematology 136: 64-69.
	Purpose: Intravenous (IV) chemotherapy has been compared with intraperitoneal (IP) chemotherapy in randomized clinical trials in advanced ovarian cancer (OC). The aim of this meta-analysis was to evaluate efficacy and toxicity of IV and IP and identify differences in outcomes.; Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and the proportion of patients with grade ≥2 acute toxicity.; Results: Four randomized clinical trials representing 2461 patients were identified. The hazard ratio (HR) of PFS was 0.88 (95% CI 0.80-0.98; p = 0.01, I 2 = 24%) in favor of IP chemotherapy. IP chemotherapy was also associated with significant OS improvement compared with IV chemotherapy, with HR of 0.79 (95% CI 0.67-0.92; p = 0.003, I 2 = 0%). Globally, grade ≥2 toxicities were reduced with IV chemotherapy.; Conclusion: This meta-analysis shows the superiority of IP chemotherapy over IV infusion in terms of clinical outcomes but toxicity rates. Its precise role in the management of advanced OC remains to be determined. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Marchetti, C., et al. (2020). "Survival and toxicity in neoadjuvant chemotherapy plus surgery versus definitive chemoradiotherapy for cervical cancer: A systematic review and meta-analysis." Cancer Treatment Reviews 83: 101945.
	Purpose: Neoadjuvant chemotherapy followed by surgery (NACT + S) has been compared with definitive chemoradiothherapy (CRT) in randomized clinical trials (RCTs) in stage IB2, IIA and IIB cervical cancer (1994 Figo stage). Our aim was to evaluate efficacy and toxicity of NACT + S and CRT and identify differences in clinical outcomes and severe toxicity frequency.; Methods: The PRISMA statement was applied. Random-effects models were used.; Results: Two RCTs representing 1259 patients were identified. NACT + S was not associated with significant OS improvement compared with CRT, with HR of 1.08 (95% CI = 0.86-1.36; p = 0.51). The HR of relapse was 1.32 (95%CI = 1.07-1.62) in favor of CRT. Severe acute toxicity was lower in CRT group.; Conclusion: This meta-analysis showed similar OS rates between treatment and CRT superiority over NACT + S in terms of DFS and severe acute toxicity. Impact on long term toxicity and quality of life remain to be proven. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Marchetti, C., et al. (2021). "The Role of Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis." Annals of Surgical Oncology 28(6): 3258-3263.
	Background: Phase 3 randomized clinical trials have been designed to compare secondary cytoreductive surgery followed by systemic therapy with systemic therapy alone for management of patients with recurrent ovarian cancer. This study aimed to compare differences in clinical outcomes between these two treatment approaches.; Methods: The PRISMA statement was applied. Only phase 3 randomized clinical trials were included in the final analysis.; Results: Three randomized clinical trials (n = 1250 patients) were identified. Secondary cytoreductive surgery was associated with significantly better progression-free survival (PFS) improvement than systemic therapy alone (hazard ratio [HR], 95% CI, 0.61-0.78; p < 0.001). The PFS benefit was greater for the complete resection subpopulation (HR, 0.56; 95% CI, 0.48-0.66; p < 0.001). The HR of overall survival (OS) was similar between the groups (HR, 0.93; 95% CI, 0.78-1.10; p = 0.37), but it was 0.73 (95% CI, 0.59-0.91) in favor of the complete resection subpopulation.; Conclusion: This meta-analysis showed secondary cytoreductive surgery as superior to systemic therapy alone in terms of PFS. The PFS and OS benefits were particularly observed for complete surgical resection. The impact on OS in the general population remains to be proven.

Marcin, M., et al. (2023). "Clinical outcomes of pelvic bone marrow sparing radiotherapy for cervical cancer: a systematic review and meta-analysis of prospective, controlled trials."
	
Marconcin, P., et al. (2021). "Effects of Exercise during Pregnancy on Postpartum Depression: A Systematic Review of Meta-Analyses." Biology 10(12).
	Postpartum depression (PPD) is a public health issue. Exercise is a nonpharmacologic alternative to deal with PPD. This study conducted a systematic review of previous meta-analyses and an exploratory pooled analysis regarding the effects of exercise on depressive symptoms among women during the postpartum period. We searched for previous meta-analyses of randomised controlled trials on PubMed, Web of Science and Scopus, date of inception to 31 May 2021. The methodological quality was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) instrument. We pooled the standardised mean differences from the selected studies. Of the 52 records screened, five were included. The results revealed a significant moderate effect of exercise on depressive symptoms among women during the postpartum period (SMD = -0.53; 95% CI: -0.80 to -0.27, p < 0.001). The pooled effect of the five meta-analyses established that exercise had a significant, small effect on depressive symptoms (SMD = -0.41; 95% CI: -0.50 to -0.32, p < 0.001). Our study indicates that exercise is effective in reducing PPD symptoms. Compared with traditional control approaches (psychosocial and psychological interventions), exercise seems have a superior effect on PPD symptoms. The implications of the present synthesis of past meta-analytical findings to guide health policies and research are discussed.

Marcu, L. G. (2023). "Circadian rhythm-based cancer therapy in randomized clinical trials." Expert Review of Anticancer Therapy: 1-11.
	INTRODUCTION: Since the 2017 Nobel prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind the biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology and the number of anatomical sites of interest in this field is increasing. This observation is in line with the clinical evidence provided by trials on head and neck, lung, colorectal and cervical cancers, as well as the presently ongoing chronotherapy trials for breast and brain cancers. AREAS COVERED: The aim of this review was to collate all randomized trials conducted on chronotherapy for various tumor sites and to appraise the evidence for chrono-oncology to advance personalized therapy. Relevant literature was collected from Pubmed/Medline databases and from clinicatrials.gov. EXPERT OPINION: Current randomized clinical trials offer a certain level of evidence for the potential of chronotherapy to personalize oncologic treatment. However, comparison of trial results is hindered by the differences in timing of radiation/chemotherapy, the absence of harmonized recommendations for treatment outcome evaluation and not ultimately, the general lack of considering gender as a matched variable in trials, which was found to be a powerful factor influencing response to treatment.

Mardon Amelia, K., et al. (2023). "Recommendations for patient education in the management of persistent pelvic pain: a systematic review of clinical practice guidelines." Pain.
	Abstract: Patient education has a critical role in the management of pain. There is considerable heterogeneity in patient education for females with persistent pelvic pain (PPP), and it remains unclear what is considered best clinical practice. Therefore, this systematic review identified and summarised recommendations for patient education in the management of benign gynaecological and urological conditions associated with PPP, as endorsed by international guidelines. Academic and relevant guideline databases were searched from inception to May 2022. Included guidelines were those for the management of benign gynaecological and urological conditions associated with PPP in adult females published in English, of any publication date, and endorsed by a professional organisation or society. Two independent reviewers screened 3097 records; 17 guidelines were included in the review. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. Recommendations were pooled using descriptive synthesis. Persistent pelvic pain guideline quality was generally poor. Three guidelines were classified as "excellent" (The NICE, RANZCOG, and ESHRE endometriosis guidelines) and therefore recommended for use. Eleven guidelines (64.7%) recommended patient education for females with PPP. Recommendations for education content were variable, however most frequently covered treatment strategies and pelvic pain diagnoses. For education delivery, the most frequent recommendations were for support groups and written/printed materials. Further research into tailored education interventions is needed for females with PPP. (Copyright © 2023 International Association for the Study of Pain.)

Mareti, E., et al. (2019). "Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis." Maturitas 124: 81-88.
	Background: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density.; Aim: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women.; Methods: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software.; Results: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I 2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I 2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I 2 95%).; Conclusion: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error. (Copyright © 2019 Elsevier B.V. All rights reserved.)

María, A., et al. (2023). "Effects of therapeutic exercise on primary dysmenorrhea: A Systematic Review."
	
Maria, E., et al. (2024). "Systematic review of the influence of pelvic floor in posture, biomechanics and function of lower extremity."
	
Maria, F. R., et al. (2022). "Effectiveness of the third wave cognitive behaviour therapy for peripartum depression treatment - A systematic review."
	
Maria Jesus, R., et al. (2022). "Efficacy of magnetic field therapy in chronic pelvic pain: A systematic review."
	
Maria Teresa, C., et al. (2023). "Role of Surgery in the Recurrent Ovarian Cancer; A Meta – Analysis."
	
Maria-Ortiz, J. K. S. and M. Bermudez-Gonzalez (2021). "Surgical treatment or early stage cervical cancer: a literatura review." Ginecologia y Obstetricia de Mexico 89(10): 802-809.
	BACKGROUND: The surgical approach to early stage cervical cancer has been shown for many years to have the same results between the open and minimally invasive routes, with fewer theoretical complications in the latter. OBJECTIVE(S): To provide a description of the current evidence on the optimal approach for the surgical treatment of early stage cervical cancer. METHODOLOGY: A bibliographic search was carried out through Pubmed, EMBASE, Web of Science and CINAHL between 2017 and 2021. RESULT(S): From what has been reviewed, it is hypothesized that open surgery allows greater anterior traction of the uterus, thus facilitating a wider resection of the uterosacral ligaments and parametria. CONCLUSION(S): The minimally invasive approach route has been shown to have worse results in terms of disease-free survival and overall survival, compared to the open route. The open approach should be reconsidered as the gold standard for patients with early-stage cervical cancer.Copyright © 2021 Asociacion Mexicana de Ginecologia y Obstetricia. All rights reserved.

Marin, L., et al. (2023). "Fertility preservation in pregnant cancer patients after first-trimester abortion: a new challenge with possible solutions." Journal of Assisted Reproduction and Genetics 40(12): 2819-2825.
	Fertility preservation in pregnant women recently diagnosed with cancer can be a challenge. Raised levels of human chorionic gonadotropin (Beta-hCG) and progesterone in this population of patients may pose a problem for the prompt initiation of controlled ovarian stimulation (COS) due to a potential negative feedback of these hormones on folliculogenesis; however, it is not feasible to wait for negativization of serum beta-hCG levels before starting controlled ovarian stimulation. In literature, very few cases have been reported regarding the preservation of fertility in pregnant women recently diagnosed with cancer. We performed an extended revision of the literature to evaluate the current knowledge of the management of fertility preservation in women with cancer and we examined two cases closely. The first case study involved a cancer patient who underwent surgical abortion at 6.5 weeks of gestation followed by administration of mifepristone to detach any minimal residual trophoblast and consequently to decrease serum beta-hCG and progesterone levels before starting COS. In the second case study, the cancer patient underwent surgical abortion at 7.1 weeks of gestation and simultaneous unilateral oophorectomy for ovarian tissue cryopreservation due to a limited time for COS. By analyzing the results of these studies, it could be hypothesized that mifepristone administration may favor the decrease of serum beta-hCG and progesterone levels in order to permit rapid initiation of COS. In cases where COS is not feasible, ovarian tissue cryopreservation should be considered as an alternative fertility preservation technique. (© 2023. The Author(s).)

Marina, L., et al. (2020). "Hormonal profile of menopausal women receiving androgen replacement therapy: a meta-analysis." Journal of endocrinological investigation 43(6): 717-735.
	Purpose: Ovarian and adrenal aging leads to a progressive decline in androgen levels and deleterious effects on the quality of life. Despite this, specific replacement is not routinely recommended in the management of women with a physiological or pathological decline in their production, mainly due to the lack of long-term follow-up safety data. The purpose of this paper was to meta-analyze and summarize the existing data about hormonal profile changes in menopausal women receiving androgen replacement treatments. Full-text articles published through May 30, 2018 were found via MEDLINE and Embase and selected according to the strict inclusion criteria.; Methods: Randomized clinical trials and case-control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. 113 papers fulfilled the inclusion criteria and 56 papers were included in the analysis. Desired data were compiled and extracted by independent observers.; Results: Androgen administration increases E1, E2, testosterone, DHEA and DHEAS serum levels, and reduces SHBG. However, the E1 and E2 increase is evident only when DHEA is administered.; Conclusions: Whatever androgen formulation we choose in postmenopausal women, the end result is a rise in testosterone serum levels. However, DHEA regimen is also associated with an increased estrogenic availability. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.

Marinone, M., et al. (2023). "Assessment of Pre-operative Vaginal Preparation for Laparoscopic Hysterectomy." JSLS : Journal of the Society of Laparoendoscopic Surgeons 27(3).
	Objective: Determine the difference in microbial growth from the vagina and uterine manipulator among patients undergoing laparoscopic hysterectomy after randomization to one of three vaginal preparation solutions (10% Povidone-iodine, 2% Chlorhexidine, or 4% Chlorhexidine).; Method: This was a prospective randomized controlled trial in an academic community hospital. Patients were ≥ 18 years old and scheduled for laparoscopic hysterectomy for benign and malignant indications.; Results: Fifty patients were identified and randomized into each arm. Prior to surgery, the surgical team prepared the vaginal field using 10% Povidone-iodine, 2% Chlorhexidine, or 4% Chlorhexidine, according to group assignment. Cultures were collected from the vagina after initial preparation, prior to the colpotomy, and on surfaces of the uterine manipulator. Bacterial count from the baseline vaginal fornix/cervical canal cultures did not differ significantly among the three groups. There was a difference in bacterial count among the second cervical canal/vaginal fornix cultures (p < 0.01), with the Povidone-iodine arm demonstrating the highest level of growth of cultures (93.8%), followed by 2% Chlorhexidine (47.4%), and 4% Chlorhexidine (20%). There was no difference in growth on the uterine manipulator handle and no difference in vaginal itching or burning was found across the three arms postoperatively.; Conclusion: Bacterial growth prior to colpotomy was the lowest with 4% Chlorhexidine followed by 2% Chlorhexidine, the Povidone-iodine group exhibited the highest bacterial growth. There was no difference in moderate to severe vaginal itching or burning. This showed that 4% Chlorhexidine is superior in reducing bacterial growth when used in laparoscopic hysterectomy.; Competing Interests: Conflict of interests: none. (© 2023 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Mariotti, G., et al. (2023). "Regenerative Medicine-Based Treatment of Stress Urinary Incontinence with Mesenchymal Stem Cells: A Systematic Review and Meta-analysis." Current Stem Cell Research and Therapy 18(3): 429-437.
	Objectives: The aim of this systematic review and meta-analysis is to analyze clinical trials on the use of autologous stem cell [SC] injection for the treatment of stress urinary incontinence [SUI] in humans. Method(s): We analyzed the effect in terms of UI improvement and continence recovery after treatment. A literature search was performed following the PRISMA guidelines. Entry into the analysis was restricted to data collected from clinical prospective trials on humans, including female and male patients with SUI. We performed a cumulative meta-analysis to explore the trend in the effect size across different groups at follow-up. Available data were compared in terms of Event Rate [ER] for the percentage of pad-free patients. Result(s): 12 trials were enclosed in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived stem cells [MDSCs] were used in 9 and adipocyte- derived SCs [ADSC] in 3 trials. Considering a random effect model, ER of continence recovery was 0.41 [95%CI 0.29 - 0.54], with similar results between the ADSC [ER, 0.40;95%CI 0.12 - 0.69] and the MDSC group [ER 0.41; 95%CI 0.27-0.55] [I2 84.69%; Q 104.69 - p<0.01] [Test of group differences p=0.96] Conclusion(s): Autologous MDSC or ADSC injection to treat SUI is demonstrated to be a safe procedure and a 41% mean rate of continence recovery is described. A higher effort should be produced to design better clinical trials, objectively evaluating either modifications inside the urethral sphincter or long-term functional results in terms of pad test and UI questionnaires.Copyright © 2023, Bentham Science Publishers. All rights reserved.

Maris, E., et al. (2021). "[Management of vulvovaginal atrophy: Physical therapies. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]." Gynecologie, obstetrique, fertilite & senologie 49(5): 414-419.
	Introduction: For some patients, local hormonal or non-hormonal treatments for genitourinary syndrome of menopause (SGUM) are contraindicated or insufficiently effective. Different physical therapies such as vaginal laser therapy, radiofrequency therapy, photobiomodulation therapy and local injection of hyaluronic acid, autologous fat (lipofilling) and platelet rich plasma (PRP) have been proposed as alternatives.; Objective: The objective of this review was to elaborate guidelines for clinical practice regarding the physical therapies proposed for management of vulvovaginal atrophy (AVV).; Methods: A systematic review of the literature on AVV management with physical therapies was conducted on Medline between January 2014 and December 2020.; Results: Regarding vaginal laser therapy, there are few randomized controlled trials and no formal conclusions can be drawn. The fractional CO2 laser did not demonstrate its superiority over local estrogen therapy. The ERBIUM:YAG laser has not been studied in randomized controlled trials. The lack of follow-up on the vaginal laser and the series of cases reporting risks of vaginal stenosis or chronic pain do not encourage recommending it as a first-line treatment. The literature concerning other physical treatments of AVV is weak concerning the genital area.; Conclusion: CO2 or ERBIUM:YAG vaginal lasers are not the first-line treatment for AVV (grade C). In patients with a contraindication to local hormonal treatments, treatment with vaginal CO2 laser or ERBIUM:YAG may be considered after information about the risks (burn, stenosis, pain) (expert opinion). The other physical treatments of SGUM have to be evaluated. (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

marjan, g., et al. (2023). "The effect of letrozole in the management of ectopic pregnancy, A systematic review."
	
Markland, A. D., et al. (2022). "Effect of vitamin D supplementation on urinary incontinence in older women: ancillary findings from a randomized trial." American Journal of Obstetrics and Gynecology 226(4): 535.e531-535.e512.
	Background: Observational studies among older women have associated vitamin D insufficiency with a greater prevalence and incidence of urinary incontinence. However, little is known about the effect of vitamin D supplementation in reducing urinary incontinence. Objective(s): This study aimed to evaluate the effects of vitamin D supplementation in reducing the frequency of urinary incontinence in older women. Study Design: We conducted an ancillary study of women aged >=55 years in the Vitamin D and Omega-3 Trial, a randomized trial with a 2x2 factorial design. Recruitment of participants started from 2011 to 2014 across 50 US states, and the follow-up of participants ended in January 2018. Randomized treatments in the parent study included (1) vitamin D3 (cholecalciferol) at a dosage of 2000 IU/d, (2) marine omega-3 fatty acids at a dosage of 1 g/d, and (3) matching placebo. Here, we analyzed women according to their randomization to vitamin D supplementation or placebo, regardless of treatment with omega-3 fatty acid supplementation. Validated frequency of urinary incontinence questions were added in year 2 of the study and were used again in year 5 at the end of trial. Prespecified ancillary outcomes included the prevalence of urinary incontinence at years 2 and 5, along with incident incontinence and progression of incontinence (from lower to higher frequency) from year 2 to year 5. Preplanned subgroup analyses examined the following outcomes: prerandomization of low serum levels of vitamin D (serum 25-hydroxyvitamin D<20 ng/mL), incontinence types, weight categories, and African American race. Result(s): Among the randomized women who provided urinary incontinence data, 11,646 women at year 2 and 10,527 women at year 5, the mean age was 70 years at year 2, with 29% racial and ethnic minorities. The prevalence of urinary incontinence that occurred at least weekly was 29% at year 2 and increased to 37% at year 5. Vitamin D supplementation compared to with placebo was not associated with lower odds of urinary incontinence occurring at least weekly at year 2 (odds ratio, 1.08; 95% confidence interval, 0.99-1.19) or year 5 (odds ratio, 1.04; 95% confidence interval, 0.94-1.15). Vitamin D supplementation compared to placebo was not associated with lower incidence or progression of urinary incontinence from year 2 to year 5: incidence (odds ratio, 1.06; 95% confidence interval, 0.83-1.35) or progression (odds ratio, 0.94; 95% confidence interval, 0.82-1.08). Women with prerandomization of low serum levels of vitamin D (n=836) did not have lower odds of the prevalence, incidence, or progression of urinary incontinence. The findings were null in subgroups according to incontinence type, women with obesity, and African American women. Only women with healthy weight randomized to vitamin D had lower odds of progression of urinary incontinence (odds ratio, 0.78; 95% confidence interval, 0.63-0.95; P=.01). Conclusion(s): Vitamin D supplementation compared to placebo for 2 to 5 years was not associated with differences in the prevalence, incidence, or progression of urinary incontinence in older women with and without adequate serum vitamin D levels, with inconsistent differences among subgroups. The findings showed that the broad use of moderate doses of vitamin D supplementation did not reduce urinary incontinence in older women.Copyright © 2021

Marko, U., et al. (2022). "The effectivity of non-hormonal therapies in the improvement of genitourinary syndrome among menopause patients."
	
Markus, M., et al. (2023). "Treatment response evaluation using FDG-PET/CT predicts survival in women with locally advanced cervical cancer." European Journal of Nuclear Medicine and Molecular Imaging 50(Supplement 1): S555.
	Aim/Introduction: Cervical cancer is the fourth most common female malignancy worldwide. [18F]-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) is routinely performed in patients with advanced cervical cancer for staging and evaluation of treatment response. The maximum standardised uptake value (SUVmax) is the most used PET parameter in clinical routine but more advanced metabolic parameters (e.g metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) may better predict survival. Our aim was to investigate the prognostic value of treatment response assessment for SUVmax, MTV and TLG, in women with locally advanced cervical cancer, using overall survival as outcome measure. Material(s) and Method(s): Women with locally advanced cervical cancer referred for radiochemotherapy at the Department of Oncology at Skane University Hospital, Sweden 2011-2019 and who underwent one PET-CT scan at baseline one at 6-month follow-up after treatment were included. Treatment response on PET-CT was assessed according to the European Organization for Research and Treatment of Cancer criteria, using SUVmax, MTV and TLG for comparison. The different treatment response outcomes were complete metabolic response (CMR), progressive metabolic disease (PMD), or either partial metabolic regression (PMR) or stable disease (SD). The response outcomes were correlated to overall survival using Cox regression analysis, with CMR as reference. Also, C-index was used to visualize the predictive potential of the different measures. Result(s): A total of 133 patients were included. Age- and clinical stage-adjusted analyses showed a statistically significant association (p<0.001) between treatment response and overall survival for SUVmax (hazard ratio (HR) for PMD 16, HR for PMR/SD 4.0), MTV (HR for PMD 16, HR for PMR/SD 2.9) and TLG (HR for PMD 16, HR for PMR/ SD 2.9). Also, C-index values from adjusted Cox models were comparable between the PET-parameters (SUVmax 0.838, MTV and TLG 0.857). Conclusion(s): Treatment response evaluation assessed with FDG-PET/CT is predictive of overall survival. The results were similar for both SUVmax, MTV and TLG.

Maroto, P., et al. (2022). "Cabozantinib for the treatment of solid tumors: a systematic review." Therapeutic advances in medical oncology 14: 17588359221107112.
	Background: Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.; Methods: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies ( n < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.; Results: Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.; Conclusion: The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.; Competing Interests: Conflict of interest statement: PM is on advisory boards for Astellas, AstraZeneca, Bayer, Bristol, Ipsen, Janssen, Novartis, Pfizer, and Roche, and has received research grants from Bayer and Roche. CP has an advisory role with AstraZeneca, Bristol Myers Squibb, Eisai, EUSA Pharma, General Electric Healthcare, Ipsen, Janssen, MSD, Novartis and Pfizer; has been a speaker for Bristol Myers Squibb, EUSA Pharma, General Electric Healthcare, Ipsen, and Pfizer; has been a protocol steering committee member for Bristol Myers Squibb, Eisai and EUSA Pharma; and has provided expert testimony for EUSA Pharma and Pfizer. JC has a scientific consultancy role (speaker and advisory roles) for Advanced Accelerator Applications, Amgen, Bayer, Eisai, Exelixis, Ipsen, ITM, Merck Serono, Novartis, Pfizer, Sanofi and Sirlex, and has received research grants from Advanced Accelerator Applications, AstraZeneca, Bayer, Eisai, Novartis, and Pfizer. ABA has no interests to declare. SV reports personal fees and nonfinancial support from Bristol Myers Squibb, personal fees and nonfinancial support from Roche, personal fees from MSD, personal fees from AbbVie, nonfinancial support from OSE PHARMA, and nonfinancial support from Merck. CR-A has no interests to declare. LM is an employee of Ipsen. DC has received institutional research funding from Janssen Oncology; has received travel and accommodation expenses from AstraZeneca (Spain), Bristol Myers Squibb, Pfizer and Roche; and has a consulting or advisory role with Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ipsen, Janssen Oncology, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, and Sanofi. (© The Author(s) 20 2.)

Marra Alexandre, R., et al. (2019). "Infectious complications of laparoscopic and robotic hysterectomy: a systematic literature review and meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29(3): 518-530.
	Objective: We performed a systematic review of the literature and meta-analysis of the infectious complications of hysterectomy, comparing robotic-assisted hysterectomy to conventional laparoscopic-assisted hysterectomy.; Methods: We searched PubMed, CINAHL, CDSR, and EMBASE through July 2018 for studies evaluating robotic-assisted hysterectomy, laparoscopic-assisted hysterectomy, and infectious complications. We employed random-effect models to obtain pooled OR estimates. Heterogeneity was evaluated with I 2 estimation and the Cochran Q statistic. Pooled ORs were calculated separately based on the reason for hysterectomy (eg, benign uterine diseases, endometrial cancer, and cervical cancer).; Results: Fifty studies were included in the final review for the meta-analysis with 176 016 patients undergoing hysterectomy. There was no statistically significant difference in the number of infectious complication events between robotic-assisted hysterectomy and laparoscopic-assisted hysterectomy (pooled OR 0.97; 95 % CI 0.74 to 1.28). When we performed a stratified analysis, similar results were found with no statistically significant difference in infectious complications comparing robotic-assisted hysterectomy to laparoscopic-assisted hysterectomy among patients with benign uterine disease (pooled OR 1.10; 95 % CI 0.70 to 1.73), endometrial cancer (pooled OR 0.97; 95 % CI 0.55 to 1.73), or cervical cancer (pooled OR 1.09; 95 % CI 0.60 to 1.97).; Conclusion: In our meta-analysis the rate of infectious complications associated with robotic-assisted hysterectomy was no different than that associated with conventional laparoscopic-assisted hysterectomy. (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Marschalek, M. L., et al. (2021). "Surgical Assessment of Tissue Quality during Pelvic Organ Prolapse Repair in Postmenopausal Women Pre-Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial." Journal of Clinical Medicine 10(11).
	The aim of this prospective randomized, double-masked, placebo-controlled, multicenter study was to analyze the surgeon's individual assessment of tissue quality during pelvic floor surgery in postmenopausal women pre-treated with local estrogen therapy (LET) or placebo cream. Secondary outcomes included intraoperative and early postoperative course of the two study groups. Surgeons, blinded to patient's preoperative treatment, completed an 8-item questionnaire after each prolapse surgery to assess tissue quality as well as surgical conditions. Our hypothesis was that there is no significant difference in individual surgical assessment of tissue quality between local estrogen or placebo pre-treatment. Multivariate logistic regression analysis was performed to identify independent risk factors for intra- or early postoperative complications. Out of 120 randomized women, 103 (86%) remained for final analysis. Surgeons assessed the tissue quality similarity in cases with or without LET, representing no statistically significant differences concerning tissue perfusion, tissue atrophy, tissue consistency, difficulty of dissection and regular pelvic anatomy. Regarding pre-treatment, the rating of the surgeon correlated significantly with LET (r = 0.043), meaning a correct assumption of the surgeon. Operative time, intraoperative blood loss, occurrence of intraoperative complications, total length of stay, frequent use of analgesics and rate of readmission did not significantly differ between LET and placebo pre-treatment. The rate of defined postoperative complications and use of antibiotics was significantly more frequent in patients without LET (p = 0.045 and p = 0.003). Tissue quality was similarly assessed in cases with or without local estrogen pre-treatment, but it seems that LET prior to prolapse surgery may improve vaginal health as well as tissue-healing processes, protecting these patients from early postoperative complications.

Marschalek, M.-L., et al. (2022). "Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial." The Journal of Sexual Medicine 19(7): 1124-1130.
	Background: Local estrogen therapy (LET) has beneficial effects on genitourinary atrophy; however it is currently unclear if LET improves sexual function in postmenopausal women with pelvic organ prolapse (POP).; Aim: To evaluate if LET vs placebo results in an improved sexual function in postmenopausal women with symptomatic POP.; Methods: We performed a secondary analysis of sexual outcomes of a previous randomized controlled trial comparing LET and placebo in 120 postmenopausal women (60/group) with symptomatic POP stage ≥3 and planned prolapse surgery. Women were randomly assigned to receive local estrogen or placebo cream 6 weeks preoperatively. The effect of therapy vs placebo was assessed with ANOVA with interaction effect of time*group and a multivariable linear regression model was built to assess the impact of different variables on sexual function before therapy.; Outcomes: We evaluated the sexual function score in sexually active women of our study population using the German Pelvic Floor Questionnaire at recruitment time and again after 6 weeks of treatment.; Results: Among 120 randomized women, 66 sexually active women remained for final analysis. There was no significant difference in the change of the sexual function score over time between the treatment groups (difference in changes in score from baseline to 6 weeks for Estrogen group vs control group was -0.110 with 95% CI -0.364 to 0.144) Multivariable analysis showed that no independent risk factor for unsatisfying sexual function score could be identified.; Clinical Implications: Based on our results, LET has no beneficial effect on sexual function in postmenopausal women with POP.; Strengths and Limitations: Main strength of our study lies in the study design and in the use of a condition- specific questionnaire. As this is a secondary analysis, this study may be insufficiently powered to identify differences in sexual data between groups.; Conclusion: LET had no impact on female sexuality in postmenopausal women with POP. Marschalek M-L, Bodner K, Kimberger O, et al. Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial. J Sex Med 2022;19:1124-1130. (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Marsinach, M. S. and A. P. Cuenca (2019). "The impact of sea buckthorn oil fatty acids on human health." Lipids in Health and Disease 18(1): 145.
	The beneficial properties of fatty acids have been undervalued for several years. In contraposition, new studies reveal that fatty acids have an essential role for human health. The aim of the study is to demonstrate the clinical applications of fatty acids present in sea buckthorn oil. The composition of fatty acids found in sea buckthorn (Hippophae rhamnoides) oil is unique for this species, presenting a vast range of health benefits for humans and therefore it is highly valued by both biomedicine and the cosmetic industry. In this way, we will see the clinical effect of monounsaturated, polyunsaturated and saturated fatty acids that constitute sea buckthorn oil and how they contribute to the correct function of the organism. Despite there being studies that support the positive effects of sea buckthorn fatty acids, they are limited. Hence, most of the results obtained in this review are from studies of isolated fatty acids instead of fatty acids extracted from sea buckthorn oil. These facts permit to demonstrate the effect of sea buckthorn fatty acids separately but we lost the possibility of detecting a synergic effect of all of them. More studies are necessary to certify the clinical application of the fatty acids present in sea buckthorn oil as well as discovering possible synergies between them.Copyright © 2019 The Author(s).

Martens, M. G., et al. (2021). "A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Oteseconazole (VT-1161) Oral Capsules versus Fluconazole and Placebo in the Treatment of Acute Vulvovaginal Candidiasis Episodes in Subjects with Recurrent Vulvovaginal Candidiasis (ultraViolet)." Open forum infectious diseases 8(SUPPL 1): S66‐S67.
	Background. Recurrent vulvovaginal candidiasis (RVVC) affects nearly 138 million women globally each year. Currently there are no FDA approved treatments. The study was conducted to evaluate the efficacy of oral oteseconazole (VT‐1161) in the prevention of culture‐verified acute VVC episodes through Week 50 and compare the efficacy of oteseconazole and fluconazole in treatment of an acute VVC episode in RVVC subjects. Methods. 219 subjects with history of RVVC (≥ 3 acute episodes within prior 12 months) were enrolled at 51 US sites. The study consisted of two phases. Induction Phase: Subjects who presented with a vulvovaginal signs and symptoms score of ≥ 3 and positive KOH test identifying Candida were randomized to either: • 600 mg oteseconazole on Day 1, 450 mg oteseconazole on Day 2 and matching placebo capsules; OR • 3 sequential 150 mg doses (every 72 hours) of over‐encapsulated fluconazole together with matching placebo capsules Maintenance Phase: 185 subjects with resolved acute VVC infections (clinical signs and symptoms score of < 3) on Day 14 received: • 150 mg oteseconazole or placebo weekly for 11 weeks • then 37‐week Follow‐up period Results. Study achieved primary and secondary efficacy endpoints. Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with ≥ 1 culture‐verified acute VVC episode through Week 50 in the intent‐to‐treat (P < 0.001). The average percentage of subjects with ≥ 1 culture‐verified acute VVC episode through Week 50 was lower in the oteseconazole group (5.1%) compared to the fluconazole/ placebo group (42.2%). Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at Day 14; 93.2% oteseconazole group, 95.8% fluconazole/placebo group. The percentage of subjects who had ≥ 1 treatment‐emergent adverse event (TEAE) was similar; oteseconazole (54%), fluconazole/placebo (64%). Most TEAEs experienced were mild or moderate severity in both groups and no drug‐related SAEs or adverse effects on liver function or QT intervals. Conclusion. Oteseconazole was shown to be safe and effective in treatment of acute VVC, treatment of RVVC and prevention of recurrence of acute VVC episodes in RVVC subjects. Oteseconazole was non‐inferior to fluconazole for treatment of acute VVC in subjects with RVVC.

Marth, C., et al. (2022). "Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(1): 93-100.
	Background: Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy.; Primary Objective: To compare the efficacy and safety of first-line pembrolizumab plus lenvatinib versus paclitaxel plus carboplatin in patients with newly diagnosed stage III/IV or recurrent endometrial cancer, with measurable or radiographically apparent disease.; Study Hypothesis: Pembrolizumab plus lenvatinib is superior to chemotherapy with respect to progression-free survival and overall survival in patients with mismatch repair-proficient tumors and all patients (all-comers).; Trial Design: Phase 3, randomized (1:1), open-label, active-controlled trial. Patients will receive pembrolizumab intravenously every 3 weeks plus lenvatinib orally daily or paclitaxel plus carboplatin intravenously every 3 weeks, stratified by mismatch repair status (proficient vs deficient). Patients with mismatch repair-proficient tumors will be further stratified by Eastern Cooperative Oncology Group performance status (0/1), measurable disease (yes/no), and prior chemotherapy and/or chemoradiation (yes/no).; Major Inclusion/exclusion Criteria: Adults with stage III/IV/recurrent histologically confirmed endometrial cancer that is measurable or radiographically apparent per blinded independent central review. Patients may have received previous chemotherapy only as neoadjuvant/adjuvant therapy and/or concurrently with radiation. Patients with carcinosarcoma (malignant mixed Müllerian tumor), endometrial leiomyosarcoma, or other high grade sarcomas, or endometrial stromal sarcomas were excluded.; Primary Endpoints: Progression-free and overall survival (dual primary endpoints).; Sample Size: About 875 patients.; Estimated Dates for Completing Accrual and Presenting Results: Enrollment is expected to take approximately 24 months, with presentation of results in 2022.; Trial Registration: ClinicalTrials.gov, NCT03884101.; Competing Interests: Competing interests: CM: funded research, EU, FWF, AstraZeneca, and Roche; honoraria/expenses, Roche, Novartis, Amgen, Merck, Pharmamar, AstraZeneca, Tesaro, and GSK; consulting/advisory board, Roche, Novartis, Amgen, Merck, AstraZeneca, Pfizer, Pharmamar, Cerulean, Vertex, GSK, Seagen, and Eisai. AT: funded research, AstraZeneca, Roche, MSD, and RUSSCO; honoraria/expenses, AstraZeneca, Roche, MSD, Eisai, Biocad, and RUSSCO; consulting/advisory board, AstraZeneca, Pfizer, MSD, Eisai, Tesaro, and Biocad. SP: honoraria, MSD, Eisai, GSK, AstraZeneca, Clovis, Pfizer, Pharmamar, and Roche. LG: institutional grants from AstraZeneca, Pfizer, Merck Sharp & Dohme, Karyopharm, Tesaro, IMV, Alkermes, Clovis, ImmunoGen Inc, Roche, Mersana, Esperas, Novocure GmbH, and OncoQuest Pharmaceuticals; advisory boards, AstraZeneca, GSK, Eisai, Eisai-Merck, and Alkermes. DK: clinical trials, Roche, Lilly Oncology, Clovis, MSD, Abbvie, Takeda, Novartis, Pfizer, Array BioPharma Inc, Servier, Nektar Therapeutics, Merck Healthcare KGaA, and GlaxoSmithKline; consultancy, Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, AstraZeneca, Raffo-tecnofarma, Varifarma, and Bayer. MJR: consulting/advisory board, MSD, AstraZeneca, GSK, Pharmamar, and Roche. SF: consulting/advisory board, Akesobio; honoraria/expenses, Amgen. MM-M: consulting/advisory board, Roche, Eli-Lilly, BMS, AstraZeneca, Teva, Amgen, Bayer, and Pfizer. RB: travel expenses, Clovis Oncology, Roche, and MSD. CV: study funding for present publication from MSD; institutional grant, MSD; consulting fees, Janssen-Cilag, Roche, GSK, Atheneum Partners, Astellas Pharma, MSD, BMS, and Leo-Pharma; payment or honoraria for presentations, Janssen Cilag, Leo Pharma, and Bayer; payment or honoraria for advisory boards, Janssen Cilag, Leo Pharma, MSD, GSK, and AstraZeneca; support for travel, Roche and Pfizer. KH: funded research, MSD, Ono, Takeda, Daiichi-Sankyo, and Eisai; honoraria, Takeda, Chugai, Kyowa-Kirin, Genmab, AstraZeneca, and MSD; consulting/advisory board, MSD, Eisai, and Takeda. EB: funded research, EU, DLR, AstraZeneca, Roche Diagnostics, and Bayer; honoraria/expenses, Roche, Merck, AstraZeneca, Tesaro, GSK, Clovis, Roche Diagnostics, Molecular Health, and Eisai; consulting/advisory board, Roche, Eisai, Merck, AstraZeneca, GSK, and Clovis. JM: employee of Eisai Inc, Woodcliff Lake, New Jersey, USA. JJL: employee of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc, Kenilworth, New Jersey, USA and stockholder in Merck & Co. VM: study support (all funding to institution)/consultant/advisory board membership, Merck, Eisai, Karyopharm, AstraZeneca, Clovis, Moreo, Takeda, Zymeworks, and Genentech; supported in part by the NIH/NCI Cancer Center Support grant P30 CA008748. (© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.)

Martin, C. E., et al. (2021). "A randomized controlled trial to evaluate the use of a web-based application to manage medications during in vitro fertilization." Fertility and Sterility 116(3): 793‐800.
	Objective: To evaluate the use of a web‐based application that assists in medication management during in vitro fertilization (IVF) treatment. Design: Multicenter randomized controlled trial. Setting: University hospitals. Patient(s): Women undergoing IVF. Intervention(s): Subjects were recruited to assess quality of life during IVF and were randomly assigned to use either the OnTrack application to assist with medication management or conventional medication management. Surveys were administered at four time points. Main Outcome Measure(s): Medication surplus, incidence of medication errors, amount of patient‐initiated communication, and patient satisfaction. Result(s): A total of 153 women participated. The average number of portal messages and telephone calls was similar between groups. Twelve patients in the control group (12/69, 17.4%) and 8 patients in the case group (8/72, 11.1%) made medication errors. There were similar amounts of medication surplus in the two groups. The estimated cost of medication waste was $2,578 ± $2,056 in the control group and $2,554 ± $1,855 in the case group. Patient satisfaction was similar between the two groups. Conclusion(s): Use of a web‐based application did not decrease medication errors, medication surplus, or patient‐initiated messages. Many patients had a medication surplus, which can be an area of cost reduction during IVF. Clinical Trial Registration Number: Clinicaltrials.gov NCT03383848.

Martin, F. E., et al. (2020). "FUNCTIONAL RECOVERY IN OLDER WOMEN UNDERGOING SURGERY FOR GYNAECOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW AND NARRATIVE SYNTHESIS...British Geriatrics Society Autumn Meeting, November 6-8, 2019, Leicester, England." Age & Ageing 49: 34-34.
	INTRODUCTION: Older women are increasingly undergoing surgery for gynaecological malignancies. Although survival data is available other outcomes such as functional recovery are less well described. However older people are both more vulnerable to changes in function and often prioritise function over survival. There is limited published research examining function outside of context of sexual or urodynamic function following gynaeoncology surgery but a large body or research exists examining health-related quality of life (HrQOL) both as a pre-operative risk factor for survival and as a post-treatment outcome measure in its own right. HRQOL tools may report on physical function as a subcomponent within composite tools. This systematic review and narrative synthesis describes functional recovery after gynaeoncology surgery with respect to baseline characteristics which - if identified – could enable pre- or post-operative risk reduction. METHODS: Systematic search of MEDLINE and EMBASE databases and Cochrane Library between 1974-2018. Two reviewers independently reviewed abstracts/papers for inclusion against the following criteria: • Mean/median age >60 • Gynaeoncological treatment includes surgery (RCTs, observational or mixed methods studies). • Any measure of functional ability as defined by WHOICF classification section D1–D7 inclusive, D855, D860-79 and D9 using validated tool. • Minimum pre-operative and one post-operative measure. Results analysed and presented using narrative synthesis. RESULTS: Sixteen studies identified (7 Endometrial, 2 Ovarian, 2 Vulval, 6 mixed cancer types). 1/16 used a standalone functional assessment tool, 15/16 used Health-Related Quality of Life tools (EORTC QLQ C30 (10), FACT-G (3), SF-36 (3)) comprising items describing function. More studies showed full recovery to baseline (n=11) than incomplete recovery (n=5 including 2 reporting age as a negative association). Recovery was more likely and occurred faster in minimally-invasive surgery. 1 study demonstrated failure to recover baseline functional independence by 12 months.

Martinez, F., et al. (2022). "Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles." Human reproduction (Oxford, England) 37(12): 2777-2786.
	Study Question: Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation?; Summary Answer: The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS.; What Is Known Already: Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF.; Study Design, Size, Duration: This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample.; Participants/materials, Setting, Methods: Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 μg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy).; Main Results and the Role of Chance: FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)).; Limitations, Reasons for Caution: The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age.; Wider Implications of the Findings: The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase.; Study Funding/competing Interest(s): This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests.; Trial Registration Number: The study was registered at Clinical Trials Gov (NCT03555942). (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Martinez, F., et al. (2021). "Ovarian stimulation for oocyte donation: a systematic review and meta-analysis." Human Reproduction Update 27(4): 673-696.
	Background: Since its introduction in the 1980s, oocyte donation (OD) has been largely integrated into ART. Lately, both demand and the indications for OD have increased greatly. Oocyte donors are healthy and potentially fertile women undergoing voluntarily ovarian stimulation (OS). Selection of the optimal type of stimulation is of paramount importance in order to achieve the most favourable outcomes for the oocyte recipients, but most importantly for the safety of the oocyte donors. Objective and Rationale: This is the first systematic review (SR) with the objective to summarize the current evidence on OS in oocyte donors. The scope of this SR was to evaluate the OD programme by assessing four different aspects: how to assess the ovarian response prior to stimulation; how to plan the OS (gonadotrophins; LH suppression; ovulation trigger; when to start OS); how to control for the risk of ovarian hyperstimulation syndrome (OHSS) and other complications; and the differences between the use of fresh versus vitrified donated oocytes. Search Method(s): A systematic literature search was conducted in May 2020, according to PRISMA guidelines in the databases PubMed and Embase, using a string that combined synonyms for oocytes, donation, banking, freezing, complications and reproductive outcomes. Studies reporting on the safety and/or efficacy of OS in oocyte donors were identified. The quality of the included studies was assessed using ROBINS-I and ROB2. Meta-analysis was performed where appropriate. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for binary data with their corresponding 95% CIs. Heterogeneity between the included studies was assessed using I2 and tau statistics. Outcome(s): In total, 57 manuscripts were selected for the review, out of 191 citations identified. Antral follicle count and anti-Mullerian hormone levels correlate with ovarian response to OS in OD but have limited value to discriminate donors who are likely to show either impaired or excessive response. Five randomized controlled trials compared different type of gonadotrophins as part of OS in oocyte donors; owing to high heterogeneity, meta-analysis was precluded. When comparing different types of LH control, namely GnRH antagonist versus agonist, the studies showed no differences in ovarian response. Use of progesterone primed ovarian stimulation protocols has been evaluated in seven studies: the evidence has shown little or no difference, compared to GnRH antagonist protocols, in mean number of retrieved oocytes (MD 0.23, [95% CI 0.58-1.05], n = 2147; 6 studies; I2 = 13%, P = 0.33) and in clinical pregnancy rates among recipients (OR 0.87 [95% CI 0.60-1.26], n = 2260, I2 = 72%, P < 0.01). There is insufficient evidence on long-term safety for babies born. GnRH agonist triggering is the gold standard and should be used in all oocyte donors, given the excellent oocyte retrieval rates, the practical elimination of OHSS and no differences in pregnancy rates in recipients (four studies, OR 0.86, 95%CI 0.58-1.26; I2 = 0%). OS in OD is a safe procedure with a low rate of hospitalization after oocyte retrieval. The use of a levonorgestrel intrauterine device or a progestin contraceptive pill during OS does not impact the number of oocytes retrieved or the clinical pregnancy rate in recipients. Ultrasound monitoring seems enough for an adequate follow up of the stimulation cycle in OD. Use of fresh versus vitrified donated oocytes yielded similar pregnancy outcomes. Wider Implication(s): This update will be helpful in the clinical management of OS in OD based on the most recent knowledge and recommendations, and possibly in the management of women under 35 years undergoing oocyte vitrification for social freezing, owing to the population similarities. More clinical research is needed on OS protocols that are specifically designed for OD, especially in term of the long-term safety for newborns, effective contraception during OS, and treatment satisfaction.Copyright © 2021 The Author(s).

Martínez-Paredes, J. F. and N. Jácome-Pérez (2019). "Depression in Pregnancy." Revista colombiana de psiquiatria 48(1): 58-65.
	INTRODUCTION: Depression is the most common psychiatric morbidity in pregnancy, affecting more than 13% of pregnant women. Its diagnosis is based on the criteria established by the DSM-5 and the application of validated scales such as the Edinburgh Postnatal Depression Scale. However, there are still errors and shortcomings among healthcare professionals in the recognition, diagnosis and treatment of depression during pregnancy, with the resulting consequences and repercussions on the gestation itself or the foetus. OBJECTIVE: To present a review of depression in pregnancy, its risk factors, clinical characteristics, complications and treatment. METHODS: The PubMed and LILACS databases were used to search for manuscripts. Of the 223 articles found, 55 fulfilled the inclusion criteria. RESULTS: The prevalence of depression in pregnancy in South America is approximately 29% and the most significant risk factors are sexual abuse, pregnancy at an early age and intrafamily violence. Therefore, early diagnosis favours a reduction in risk behaviour, foetal neurodevelopmental disorders and obstetric outcomes. CONCLUSIONS: Depression in pregnancy is common condition but is underreported as its symptoms are often attributed to the pregnancy itself. The use of selective serotonin reuptake inhibitor antidepressants, particularly fluoxetine, which has not been associated with teratogenicity, is recommended, in addition to the implementation of non-pharmacological treatment such as psychotherapy, mindfulness and aerobic exercise. Educating healthcare professionals will facilitate the correct diagnosis and treatment of this condition.

Martins, M. V., et al. (2022). "Effects of trying to conceive using an every-other-day strategy versus fertile window monitoring on stress: a 12-month randomized controlled trial." Human reproduction (Oxford, England) 37(12): 2845-2855.
	STUDY QUESTION: Can animation videos on how to optimize the chances of pregnancy influence stress, anxiety, depression and sexual functioning of individuals trying to conceive (TTC)? SUMMARY ANSWER: There were no differences between those educated to have intercourse every other day, on the fertile window and a control group (CG), and depression and sexual dysfunction significantly increased over time for all arms. WHAT IS KNOWN ALREADY: Recent findings indicate that time to pregnancy can be significantly shortened by targeting the fertile period, but some reproductive care guidelines recommend instead the practice of intercourse every other day on the basis that it is less stressful to the couple. Evidence to support guidelines on how to preserve well-being and psychosocial adjustment and optimize pregnancy chances is lacking. STUDY DESIGN, SIZE, DURATION: We conducted a prospective, double-blinded, three-arm randomized controlled trial between July 2016 and November 2019. Participants were randomized to either not having any stimulus (CG) or visualizing a short animated video explaining how to improve chances of pregnancy by having intercourse every other day (EOD group), or by monitoring the fertile window (FWM group). Assessments were made before the intervention (T0), and 6 weeks (T1), 6 months (T2) and 12 months after (T3), with follow-ups censored in case of pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were childless individuals of reproductive age actively TTC and not diagnosed or unaware of a condition that could prevent spontaneous pregnancy. Individuals were excluded from recruitment if they had previous children or had a condition preventing spontaneous pregnancy. Our primary outcome was stress and secondary outcomes included anxiety, depression, sexual functioning and pregnancy. Primary analyses were performed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 450 randomized participants 127 were educated to use an every-other-day strategy, 135 to monitor the fertile window, and 134 received no intervention. Groups were similar regarding demographics and months TTC. Repeated measures analysis revealed that there were no significant interaction effects of psychological and sexual well-being between groups over time (P > 0.05). Significant time effects were revealed for stress (F(3,855) = 4.94, P < 0.01), depression (F(3,855) = 14.22, P < 0.01) and sexual functioning (time effects P values <0.001 for female sexual functioning dimensions and <0.002 for male dimensions), but not for anxiety (F(2,299) = 0.51, P > 0.05). Stress levels lowered after 6 months (P < 0.001) and returned to baseline levels at the 1-year follow-up. Depressive symptomatology significantly increased at 6 weeks (P = 0.023), and again 1 year after (P = 0.001). There were also significant decreases in all female sexual functioning dimensions (desire, satisfaction, arousal, pain, orgasm and lubrication). In men, there were significant variations in orgasm, intercourse satisfaction and erectile function, but not desire and sexual satisfaction. Revealed pregnancy rates were 16% for participants in the EOD group, 30% for the FWM group and 20% for the CG. Pregnancies were not significantly different between arms: EOD vs FWM (odds ratio (OR) 2.32; 95% CI 0.92-5.83); EOD vs CG (OR 0.74; 95% CI 0.30-1.87); and FWM vs CG (OR 1.71; 95% CI 0.70-4.18). LIMITATIONS, REASONS FOR CAUTION: Participants were recruited after transitioning to procreative sex. The study might be prone to bias as almost 30% of our sample fulfilled the chronological criterion for infertility, and other reproductive strategies could have been tried over time before recruitment. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that stress does not arise from feeling pressured on the fertile period and that advice on timing of intercourse might have to be personalized. The increasing levels of depression and sexual dysfunction over a year emphasize the crucial role of preconception care and fertility counseling in promoting psychological and sexual well-being. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by European Union Funds (FEDER/COMPETE-Operational Competitiveness Programme) and by national funds (FCT-Portuguese Foundation for Science and Technology) under the projects PTDC/MHC-PSC/4195/2012 and SFRH/BPD/85789/2012. TRIAL REGISTRATION NUMBER: NCT02814006. TRIAL REGISTRATION DATE: 27 June 2016. DATE OF FIRST PATIENT’S ENROLLMENT: 19 July 2016.

Martorana, F., et al. (2024). "A review and metanalysis of metronomic oral single-agent cyclophosphamide for treating advanced ovarian carcinoma in the era of precision medicine." Journal of Oncology Pharmacy Practice 30(1): 173-181.
	Objective: Oral metronomic cyclophosphamide has been used as a single agent or in combination with other drugs for several solid tumors with interesting results in disease palliation and mild to moderate toxicity, notably in patients with recurrent epithelial ovarian cancer (EOC) progressing after systemic chemotherapy. In this paper, we report a review and a metanalysis of heterogeneous data published up to date. Data sources: The literature search was restricted to single-agent MOC. The analysis was conducted through March 2023 by consulting PubMed, Embase, Google Scholar, and The Cochrane Library databases. Research string and Medical Subject Headings included "ovarian tumor," "ovarian carcinoma," or "ovarian cancer," "fallopian tube cancer," "primary peritoneal cancer," "oral chemotherapy," and "metronomic cyclophosphamide." All articles were assessed for quality by at least two investigators independently, and a < 18 patients sample size cutoff was chosen as a lower limit with a Cohen's kappa statistical coefficient for accuracy and reliability. Metanalysis of selected papers was carried out according to a fixed model. Data summary: The percentage of agreement between investigators on literature study selection was very high, reaching 96.9% with a Cohen's k of 0.929. MOC pooled objective response rate (ORR) and disease control rate for recurrent or platinum-refractory ovarian cancer were 18.8% (range 4-44%) and 36.2% (range 16-58.8%), respectively. The mean progressive-free survival and overall survival were 3.16 months (range 1.9 to 5.0 months) and 8.7 months (range 8 to 13 months), respectively. The fixed model metanalysis of selected studies showed a 16% median ORR (12-20% CI, p < 0.001). Conclusion(s): Single-agent oral cyclophosphamide in EOC holds promise as a treatment option, even in the era of precision medicine. Genetic factors, such as DNA repair gene polymorphisms, may influence treatment response. Combining cyclophosphamide with biological agents such as PARP inhibitors or immunotherapy agents is an area of active investigation.Copyright © The Author(s) 2023.

Maruccia, S., et al. (2023). "A NOVEL DEVICE FOR SELECTIVE EXTRACORPOREAL MAGNETIC INNERVATION: RESULTS ON WOMEN WITH STRESS URINARY INCONTINENCE." Journal of urology 209(Supplement 4): e520.
	INTRODUCTION AND OBJECTIVE: The international guidelines include conservative and surgical treatments for stress urinary incontinence on women. Extracorporeal magnetic stimulation (EMS) is a conservative option for pelvic floor disorders. MS is a non-invasive therapeutic device that interacts with the neuromuscular tissue through an electromagnetic field, thus inducing intense contractions that stimulate pelvic floor muscles. Recently, the TOP Flat Magnetic Stimulation (TOP FMS) has been developed as new generation of traditional magnetic chairs. This new technology generates electromagnetic fields with a homogenous profile optimized for the stimulation of the pelvic area, allowing greater recruitment of muscle fibres without creating areas of uneven stimulation intensity. We sought to assess the short-term outcomes, both subjective and objective, in women suffering from SUI. METHOD(S): In this non-randomized trial, a clinical interview was performed to investigate the presence of isolated or predominant stress urinary incontinence (SUI), subsequently confirmed by a stress test. Urogenital examination was used to exclude significant prolapse (POP-Q stage >2 or higher). Patients could choose to receive the new treatment (eight sessions of 25 minutes of TOP FMS in one month) or home-based, unsupervised, non-personalized pelvic floor muscles training (PFMT) according to the International Urogynecological Association leaflets for one month. At baseline (T0) and at the end of the treatments (T1) the International Consultation on Incontinence Questionnaire-Short Form questionnaire (ICIQ-SF) and the Incontinence Impact Questionnaire (IIQ-7- SF) were administered. The stress test was performed again after treatment and the Patient Global Impression of Improvement (PGI-I) questionnaire was administered. RESULT(S): 50 patients were enrolled (1:1 allocation ratio). Improved PGI-I scores were reported by 72% intervention patients vs 20% controls (p<0.001) after 1 month. According to the stress test at T1 (1 month), the objective cure rate resulted 40% for TOP FMS and 0% for PFMT (p<0.001). Significant improvements were observed in the TOP FMS, IIQ-7 and ICIQ-SF scores (p<0.05) but not in the FSFI-19 scores. No adverse events were reported either with TOP FMS or PFMT. CONCLUSION(S): The TOP FMS appears promising in patients with isolated or predominant SUI, compared to than unsupervised, nonindividualized PFMT, in treating SUI in women.

Maruyama, S., et al. (2020). "Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease?" European Journal of Obstetrics and Gynecology and Reproductive Biology 253: 191-197.
	Adenomyosis and endometriosis are common gynecological disorders, but their pathophysiology is still under debate. The aim of this review is to discuss whether adenomyosis and endometriosis represent two different entities or different phenotypes of a single disease. We searched PubMed electronic databases published between January 2000 and April 2020. Endometriosis is classified into three phenotypes; superficial peritoneal disease (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) lesions. Adenomyosis presents several different subtypes, including intrinsic adenomyosis, extrinsic adenomyosis, adenomyosis externa and focal adenomyosis located in the outer myometrium (FAOM). Human uterus is embryologically composed of archimetra, originating from the Mullerian duct, and neometra, arising from the non-Mullerian duct, and adenomyosis and endometriosis are diseases of archimetra. The outer myometrial layer of the uterus is composed of highly differentiated smooth muscle cells (SMCs), while the inner myometrial cells are immature. Inappropriate uterine contractions can cause retrograde menstruation and chronic inflammation in the pelvic cavity, then influencing the development of pelvic endometriosis. Furthermore, hyperperistalsis results in physiological and pathological changes to the endometrial-myometrial junctional barrier, allowing invagination of the normal endometrial tissue into the inner myometrial layer. This can trigger the development of intrinsic adenomyosis. There are insufficient data available to draw conclusions, but extrinsic adenomyosis may result from pelvic endometriosis and FAOM from rectal and bladder DIE/adenomyosis externa. In conclusions, this paper contributes to the debate in the possibility that adenomyosis and endometriosis represent different phenotypes of a single disease.Copyright © 2020 Elsevier B.V.

Masciullo, L., et al. (2021). "A deep insight into pelvic pain and endometriosis: a review of the literature from pathophysiology to clinical expressions." Minerva Obstetrics and Gynecology 73(5): 511-522.
	Introduction: Endometriosis is a chronic inflammatory disease that affects approximately 10% of women of reproductive age. Its clinical manifestations are highly heterogeneous, but pelvic pain is the most frequent, causing functional disability. Cyclic or acyclic chronic pelvic pain (CPP), dysmenorrhea and dyspareunia are frequent symptoms which often compromise all aspects of the women's quality of life (QoL). The pathophysiology of endometriosis-related pain is extremely complex and not always clear. The aim of this systematic review was to focus on recent updates on the clinical presentation, the pathophysiology and the most important mechanisms involved in the pathogenesis of pelvic pain in endometriosis.; Evidence Acquisition: A literature search in the Cochrane library, PubMed, Scopus and web of Science databases has been performed, identifying articles from January 1995 to November 2020.; Evidence Synthesis: Several processes seem to be involved in the pathogenesis of pain, but many aspects are still unclear. Scientific evidence has shown that a correlation between pain severity and stage of endometriosis rarely occurs, whereas there is a significant correlation between pain and the presence of deep endometriosis. Onset and intensity of pain may be due to a complex process involving central sensitization and peripheral activation of nociceptive pathways as well as dysfunction of the immune system and of the hypothalamic-pituitary-adrenal (HPA) axis.; Conclusions: A deeper understanding of these different pathogenetic mechanisms may improve future treatments in women with painful endometriosis.

Massin, N., et al. (2022). "The BISTIM study: first RCT comparing dual ovarian stimulation on the same cycle (duostim) vs 2 conventional ovarianstimulations in poor ovarian responders undergoing IVF." Human reproduction (Oxford, England) 37: i41.
	Study question: Is the number of cumulated oocytes with dual ovarian stimulation on the same cycle (duostim) higher compared to 2 consecutive antagonist cycles in poor responders? Summary answer: Considering the number of total and mature oocytes collected in poor ovarian responders, there is no benefit of duostim vs two consecutive antagonist cycles. What is known already: Several waves of follicular development exist on the same cycle. Recent studies have shown the ability to obtain oocytes with equivalent quality in the luteal phase, even after a previous ovarian stimulation in the follicular phase. During stimulation, smaller follicles are recruited and sensitized, which may increase the selection of follicles available on the second stimulation. In poor ovarian responders (POR) this potentialization may have a great interest, as 2 stimulations on the same cycle could give a higher number of oocytes compared to two conventional stimulations. However, these preliminary data need to be confirmed with a randomized controlled trial. Study design, size, duration: This is a multicenter, open‐labeled randomized control trial (2018, september‐2021, march). The primary objective was to demonstrate that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) lead to the retrevial of 1.5 more oocytes than the cumulative number of oocytes from two consecutive conventional stimulation, in POR women. According to this hypothesis, 44 patients were needed in each group. Participants/materials, setting, methods: 88 POR women, defined with Bologna criteria (AFC≤5 and/or AMH≤1.2ng/ml and ≤3 oocytes if previous IVF) were randomized, 44 in duostim group (D) and 44 in conventional group (C). Fertistart Kit®300IU/day with antagonist protocol was used except in luteal phase stimulation of group D. In group D, oocytes were pooled and inseminated after the second retrieval, with freeze all embryos. Fresh transfer was performed in group C. The analysis is presented in intention to treat. Main results and the role of chance: There was no difference between the groups regarding demographics, ovarian reserve markers (AFC, AMH) and stimulation parameters. The mean number of cumulated oocytes retrieved with 2 ovarian stimulation was not statistically different in group D and C, respectively 5.0+/‐3.4 and 4.6+/‐3.4 (p=0.56). The mean number of cumulated mature oocytes was not statistically different, 3.7+/‐3.3 in group D vs 3.1+/‐3.0 in group C (p=0.38). The mean number of embryos was significantly lower in the group D, 0.8+/‐1.3 vs group C 1.6+/‐1.3 (p<0.01). There was no statistical difference of the mean number of oocytes retrieved per cycle in cycle 1 vs cycle 2 in both group D and C. The delay, between the first and the second day 1 of stimulation was statistically different in group D 14.4 days (10‐19) vs group C 90.6 (28‐232). The ongoing pregnancy rate in group D 17.9% (7/39) was not statistically different with group C 29.3% (12/41), (p=0.23). And the mean time to ongoing pregnancy tends to be longer in group D (144 days) vs group C (115 days) but was not statistically different (p=0.21). Limitations, reasons for caution: The RCT was impacted by Covid pandemia and stop of IVF activities for 10 weeks. Delays were recalculated to exclude this period, however one women in group D cannot have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte pick‐up in group C. Wider implications of the findings: In routine practice, the benefit of duostim in patients with POR is not confirmed. Firstly, because there is no potentialization on the number of oocyte retrieved in luteal phase after follicular phase stimulation. Secondly, because the freeze all strategy avoids a pregnancy with fresh embryo transfer after the first cycle.

Massoth, C., et al. (2021). "Impact of opioid-free anaesthesia on postoperative nausea, vomiting and pain after gynaecological laparoscopy - A randomised controlled trial." Journal of Clinical Anesthesia 75: 110437.
	Study objective: Opioid‐free anaesthesia may enhance postoperative recovery by reducing opioid‐related side effects such as nausea, hyperalgesia or tolerance. The objective was to investigate the impact of multimodal opioid‐free general anaesthesia on postoperative nausea, vomiting, pain and morphine consumption compared to the traditional opioid‐based approach. Design: This study was conducted as a prospective parallel‐group randomised controlled trial. Setting: Perioperative Care. Patients: 152 adult women undergoing elective inpatient gynaecological laparoscopy. Interventions: Patients were randomly assigned for opioid‐free anaesthesia (Group OF) with dexmedetomidine, esketamine and sevoflurane or to have opioid‐based anaesthesia (Group C) with sufentanil and sevoflurane. Measurements: Primary outcome was the occurrence of nausea within 24 h after surgery. Patients were assessed for the incidence and severity of PONV, postoperative pain and morphine consumption and recovery characteristics. Main results: Patients in both groups had comparable clinical and surgical data. 69.7% of patients in the control group and 68.4% of patients in the opioid‐free group met the primary endpoint (OR 1.06, 95% Confidence Interval (CI) (0.53; 2.12) p = 0.86). The incidence of clinically important PONV defined by the PONV impact scale was 8.1% (Group C) vs 10.5% (OF); p = 0.57). Antiemetic requirements, pain scores and morphine consumption were equivalent in both groups. Postoperative sedation was significantly increased in group OF (p < 0.001), and the median length of stay at the post‐anaesthesia care unit was 69.0 min (46.5?113.0) vs 50.0 (35.3?77.0) minutes in the control group (p < 0.001). Conclusions: Opioid‐free multimodal general anaesthesia is feasible but did not decrease the incidence of PONV, or reduce pain scores and morphine consumption compared to an opioid‐containing anaesthetic regimen.

Mastwyk, S., et al. (2019). "The impact of pelvic organ prolapse and/or continence surgery on pelvic floor muscle function in women: A systematic review." Neurourology and Urodynamics 38(6): 1467-1481.
	Aims: To systematically review the evidence for the effect of pelvic organ prolapse (POP) and/or continence surgery on pelvic floor muscle (PFM) morphometry and function in women, and to investigate whether a relationship exists between PFM measures and clinician-reported objective pelvic floor outcomes postoperatively.; Methods: Six electronic databases were searched until March 2018. Studies were included if they examined the effect of POP and/or continence surgery on the PFM in women, and reported pre- and postoperative data. Methodological quality was assessed using a modified Downs and Black checklist. Three meta-analyses were planned based on postoperative follow-up time.; Results: Twenty-one studies met the inclusion criteria. Varied surgical interventions and 33 different PFM measures were represented. The methodological quality of included studies varied considerably. The 0 to 6 weeks postoperative meta-analysis showed no statistically significant change in PFM function (SMD = 0.04; 95% confidence interval [CI] = -0.26 to 0.33). This was consistent at 3 and 6 or more months (SMD = 1.13; 0.35 95% CI = -0.34 to 2.60, - 0.42 to 1.12 respectively). None of the included studies investigated the relationship between PFM measures and clinician-reported objective outcomes postoperatively.; Conclusions: This review did not show a clear effect of POP and/or continence surgery on PFM morphometry or function in women and was unable to show a relationship with outcomes such as objective prolapse score and urodynamic findings. This could be because surgery does not measurably impact on the PFM or due to the poor quality and heterogeneity of studies. Future well-designed research is needed to specifically investigate change in the PFM following surgery. (© 2019 Wiley Periodicals, Inc.)

Máté, É., et al. (2022). "Investigating the effects of platelet-rich plasma (PRP) treatment on fertility for women with diminished ovarian reserve."
	
Mathevet, P., et al. (2021). "Sentinel lymph node biopsy and morbidity outcomes in early cervical cancer: Results of a multicentre randomised trial (SENTICOL-2)." European journal of cancer (Oxford, England : 1990) 148: 307-315.
	INTRODUCTION: Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated. MATERIALS AND METHODS: In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point. RESULTS: A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm). CONCLUSION: SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.

Matingou, C. K., et al. (2023). "Impact of Flutamide on Wake vs. Sleep LH Pulse Frequency in PCOS: An Interim Analysis." Journal of the Endocrine Society 7(Supplement 1): A899.
	Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. PCOS is also associated with luteinizing hormone (LH) excess, in part related to persistently high gonadotropin-releasing hormone (GnRH) pulse frequency. Furthermore, late pubertal girls with obesity and hyperandrogenemia did not exhibit sleep-associated decreases in LH (GnRH) pulse frequency when studied during the follicular phase, in contrast to non-hyperandrogenemic controls with or without obesity (JCEM 2014;99:2887-96). We therefore aimed to test two hypotheses: (1) sleep-associated reductions in LH pulse frequency are less pronounced in adult PCOS compared to late-follicular controls; and (2) sleep-associated reductions in LH pulse frequency are normalized in PCOS with 4 weeks of flutamide (androgen-receptor antagonist) pretreatment. To date, we have studied 5 women with PCOS (median age 30 y, BMI 42.6 kg/m2) and 5 ovulatory controls (median age 22 y, BMI 23.2 kg/m2). Subjects underwent two separate 16-hour frequent-blood-sampling studies to characterize pulsatile LH secretion, once after flutamide pretreatment (250 mg BID x 4 weeks) and once after placebo (PBO) pretreatment (BID for 4 weeks). In each study, 1500-2300 h and 2300-0700 h were designated the wake and sleep periods, respectively. The order of flutamide and PBO administration was randomized, and treatment allocation was switched after the first admission per a cross-over design. Controls were studied on cycle days 7-10, while those with PCOS were studied no earlier than cycle day 7. Serum progesterone concentrations were < 1.5 ng/ dl for all admissions. With PBO pretreatment, participants with PCOS and controls exhibited the following: wake LH pulse frequency 1.19 (1.08-1.33) (median [interquartile range]) and 1.22 (0.97-1.27) pulses/h, respectively; sleep LH pulse frequency 0.93 (0.78-1.28) and 0.83 (0.78-0.99) pulses/h, respectively; and wake-to-sleep change in LH pulse frequency of -19.4 (-21.9 to +2.9) and -15.5 (-31.8 to -12.0) percent, respectively. For participants with PCOS, pretreatment with flutamide was associated with the following changes compared to PBO: wake LH pulse frequency +0.01 (-0.06 to +0.03) pulses/h; sleep LH pulse frequency +0.06 (+0.01 to +0.07) pulses/h; and wake-to-sleep LH pulse frequency change +5 (+7 to -12) percent. None of these differences were statistically significant by conservative nonparametric testing. We conclude that this interim analysis does not offer any indication that wake- and sleep-associated LH pulse frequencies are different between PCOS and late-follicular controls, nor does it suggest clear differences in wake-to-sleep changes in late-follicular LH pulse frequency between groups. Furthermore, this analysis does not seem to offer any indication that flutamide alone alters wake- and/or sleep-associated LH pulse frequencies in PCOS.

Matorras, R., et al. (2023). "Comparison of the Administration of 150 or 75 IU of Recombinant LH in Agonist ICSI Cycles Stimulated with Recombinant FSH in Women Aged 35-39: A Comparative Study." Journal of Reproduction and Infertility 24(4): 269-278.
	Background: The purpose of the study was to assess whether the coadministration of 150 IU of recombinant LH instead of 75 IU in women aged 35-39 improves the results in agonist ICSI cycles stimulated with 300 IU of recombinant FSH. Method(s): In this study, two ovarian stimulation protocols coexisted which were identical except in the administered dose of recombinant LH, for which some patients received 150 IU (n=231) and some received 75 IU (n=216). Both groups received 300 IU of recombinant FSH. Gonadotropins were reimbursed by the National Health System. Statistical analysis was performed by Student's t test, chi2, and ANCOVA. Significance level was established at p=0.05. Result(s): The number of retrieved oocytes was slightly higher in the 300/150 group (9.06+/-5.53 vs. 8.61+/-5.11), but the differences were not significant. Results were similar with the number of metaphase II oocytes (7.18+/-4.86 vs. 6.72+/-4.72) and the number of fertilized oocytes (4.64+/-3.2 vs. 4.23+/-2.72). The per-transfer clinical pregnancy rates exhibited close similarity between both groups (32.84% vs. 32.46%), as did the per-transfer live birth rates (29.90% vs. 30.37%) and the implantation rate. The rate of hyperstimulation syndrome (OHSS) as well as the rate of cancellation due to OHHS risk was similar in both groups. There was also no difference in the miscarriage rate. When results were expressed by per started cycle or by oocyte pick-up, the results remained very similar in both groups. Conclusion(s): In women aged 35-39 undergoing ovarian stimulation with recombinant FSH in antagonist cycles, the coadministration of 75 or 150 UI of recombinant LH did not influence pregnancy rates. However, a slight increase in the number of retrieved oocytes should not be disregarded.Copyright © 2023, Journal of Reproduction & Infertility. All rights reserved.

Matsuda, Y., et al. (2023). "[Ⅰ. Dose-Dense Chemotherapy in Ovarian Cancer]." Gan to kagaku ryoho. Cancer & chemotherapy 50(2): 153-156.
	
Matsuoka, P. K., et al. (2019). "Occult Urinary Incontinence Treatment: Systematic Review and Meta-analysis-Brazilian Guidelines. Tratamento de incontinencia urinaria oculta: revisao sistematica e metanalise - diretrizes brasileiras." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 41(2): 116-123.
	Objective To evaluate if performing anti-incontinence procedures during surgical anterior and/or apical prolapse correction in women with asymptomatic urinary incontinence (UI) may prevent stress urinary incontinence (SUI) postoperatively. Methods We have performed a systematic review of articles published in the PubMed, Cochrane Library, and Lilacs databases until March 31, 2016. Two reviewers performed the data collection and analysis, independently. All of the selected studies were methodologically analyzed. The results are presented as relative risk (RR), with a 95% confidence interval (CI). Results After performing the selection of the studies, only nine trials fulfilled the necessary prerequisites. In the present review, 1,146 patients were included. Altogether, the review included trials of three different types of anti-incontinence procedures. We found that performing any anti-incontinence procedure at the same time of prolapse repair reduced the incidence of SUI postoperatively (RR = 0.50; 95% CI: 0.28–0.91). However, when we performed the analysis separately by the type of anti-incontinence procedure, we found different results. In the subgroup analysis with midurethral slings, it is beneficial to perform it to reduce the incidence of SUI (RR = 0.08; 95% CI: 0.02–0.28). On the other hand, in the subgroup analysis with Burch colposuspension, there was no significant difference with the control group (RR = 1.47; 95% CI: 0.28–7.79]). Conclusion Performing any prophylactic anti-incontinence procedure at the same time as prolapse repair reduced the incidence of SUI postoperatively. The Burch colposuspension did not show any decrease in the incidence of SUI postoperatively.

Matsusaki, K., et al. (2022). "Clinical practice guideline for the treatment of malignant ascites: section summary in Clinical Practice Guideline for peritoneal dissemination (2021)." International Journal of Clinical Oncology 27(1).
	Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions.Copyright © 2021, The Author(s).

Matsuzaki, S., et al. (2020). "Management of Stage IIB Cervical Cancer: an Overview of the Current Evidence." Current oncology reports 22(3): 28.
	Purpose of Review: To review and discuss the present evidence of surgery- and radiation-based treatment strategies for stage IIB cervical cancer.; Recent Findings: Recently, two randomized controlled trials compared the efficacy of neoadjuvant chemotherapy followed by radical hysterectomy (NACT + RH) with that of concurrent chemoradiotherapy (CCRT) for stage IB3-IIB cervical cancer. When these studies were combined (N = 1259), NACT + RH was associated with a shorter disease-free survival [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.13-1.64], but with a similar overall survival (HR 1.11, 95% CI 0.90-1.36) when compared with the findings for CCRT. Stage-specific analysis for stage IIB cervical cancer demonstrated that disease-free survival was significantly worse with NACT + RH than with CCRT (HR 1.90, 95% CI 1.25-2.89); however, no significant difference was observed for stage IB3-IIA cervical cancer. Based on the results of recent level I evidence, the standard treatment for stage IIB cervical cancer remains CCRT.

Matsuzaki, S., et al. (2021). "Surgical and oncologic outcomes of hyperthermic intraperitoneal chemotherapy for uterine leiomyosarcoma: A systematic review of literature." Gynecologic Oncology 161(1): 70-77.
	Objective: To examine the perioperative and survival outcomes in women with disseminated peritoneal uterine leiomyosarcoma (uLMS) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).; Methods: A comprehensive systematic review of literature was conducted using multiple public search engines, PubMed, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. Women with disseminated peritoneal uLMS treated with CRS-HIPEC were analyzed. Perioperative morbidity and mortality rate as well as oncologic outcomes related to CRS-HIPEC were assessed.; Results: Ten studies met the inclusion criteria from 2004 to 2020, including 8 case series (n=28) and 2 original articles (n=47). Of the 75 patients, 68 (90.7%) were women with uLMS whereas 7 women were non-uLMS. Of these, 64 (85.3%) had recurrent disease, and 39 (52.0%) received chemotherapy or radiotherapy prior to CRS-HIPEC. The perioperative mortality rate was 4.0% (intraoperative 1.3%, and postoperative 2.7%), and postoperative complications (grade ≥3) rate ranged 21.4-22.2%. With regard to HIPEC regimens (n=75), cisplatin was most frequently used (n=55, 73.3%) followed by melphalan (n=17, 22.7%) and others (n=3, 4.0%). Among the two observational studies, the median overall survival after CRS-HIPEC treatment was 29.5-37 months. In one limited comparative effectiveness study (n=13), albeit statistically non-significant CRS-HIPEC was associated with higher progression-free survival versus CRS alone (3-year rates, 71.4% versus 0%, P=0.10). When the HIPEC regimens were compared, melphalan use was associated with decreased uLMS-related mortality compared to a cisplatin-based regimen, but the association was not statistically significant (hazard ratio 0.35, 95% confidence interval 0.04-3.05, P=0.35).; Conclusion: Effectiveness of CRS-HIPEC for disseminated peritoneal uLMS is yet to be determined. As interpretation of the available data on survival is limited due to small sample sizes or the lack of an active comparator, further study is warranted to examine the safety and survival effect of CRS-HIPEC in disseminated peritoneal uLMS. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Matta, R., et al. (2023). "Predicting Mirabegron Treatment Response in Patients with Overactive Bladder: A Post Hoc Analysis of Data from Clinical Trials." European Urology Focus 9(6): 957-965.
	Background: Many patients discontinue overactive bladder (OAB) treatment because of unmet treatment expectations and/or tolerability issues. Objective(s): To develop a model for predicting the individual treatment response to mirabegron using patient baseline characteristics. Design, setting, and participants: This was a post hoc analysis of data from eight global phase 2/3, double-blind, randomized, placebo- or active-controlled trials of mirabegron in adult patients with OAB. Intervention(s): Mirabegron 50 mg once-daily monotherapy for >=12 wk. Outcome measurements and statistical analysis: Primary efficacy outcomes were the change in the mean number of micturitions and the number of incontinence episodes/24 h after 12 wk of treatment. Secondary efficacy outcomes were the change in the mean number of urgency episodes/24 h and the change in Symptom Bother score after 12 wk of treatment. Baseline demographic characteristics, OAB-related characteristics, and intrinsic and extrinsic factor variables were used to create multivariable linear regression models to predict the primary and secondary outcomes. Results and limitations: Data for 3627 patients were included. The predicted effect of mirabegron 50 mg was an average of 2.5 fewer micturition episodes/24 h (95% confidence interval -2.85 to -2.14) and 0.81 fewer incontinence episodes/24 h (95% confidence interval -1.15 to -0.46) from baseline to week 12. A higher number of urgency episodes was predictive of a larger reduction in micturition episodes; body mass index (BMI) >=30 kg/m2, OAB symptoms for >=12 mo, and incontinence at baseline were predictive of a smaller reduction. Mixed stress/urgency incontinence and more than five urgency episodes per day were predictive of greater reductions in incontinence episodes. Reductions in urgency episodes and Symptom Bother score were also predicted with mirabegron. Limitations include the exclusion of placebo groups from the analysis and the use of clinical trial rather than real-world data. Conclusion(s): Data from the predictive models provide new insights into the effects of modifiable factors (such as BMI) and nonmodifiable factors on treatment outcomes with mirabegron 50 mg. Patient Summary: This study aimed to identify factors that could predict how patients with overactive bladder respond to mirabegron treatment to help doctors effectively treat this condition. Mirabegron treatment was associated with a lower number of urinations and occurrences of urinary incontinence per day. Factors associated with worse responses to the medication included being obese.Copyright © 2023 The Authors

Matthews, C. (2022). "Multicenter trial to evaluate single-incision slings." Urology times 50(8): 18‐19.
	
Matthews, C. A., et al. (2023). "Long-term mesh exposure after minimally invasive total hysterectomy and sacrocolpopexy." International Urogynecology Journal 34(1): 291-296.
	Introduction and hypothesis: The objective was to evaluate total and incident mesh exposure rates at least 2 years after minimally invasive total hysterectomy and sacrocolpopexy. Secondary aims were to evaluate surgical success and late adverse events. Method(s): This extension study included women previously enrolled in the multicenter randomized trial of permanent vs delayed-absorbable suture with lightweight mesh for > stage II uterovaginal prolapse. Owing to COVID-19, women were given the option of an in-person (questionnaires and examination) or telephone visit (questionnaires only). The primary outcome was total and incident suture or mesh exposure, or symptoms suggestive of mesh exposure in women without an examination. Secondary outcomes were surgical success, which was defined as no subjective bulge, no prolapse beyond the hymen, and no pelvic organ prolapse retreatment, and adverse events. Result(s): A total of 182 out of 200 previously randomized participants were eligible for inclusion, of whom 106 (58%) women (78 in-person and 28 via questionnaire only) agreed to the extension study. At a mean of 3.9 years post-surgery, the rate of mesh or suture exposure was 7.7% (14 out of 182) of whom only 2 were incident cases reported after 1-year follow-up. None reported vaginal bleeding or discharge, dyspareunia, or penile dyspareunia. Surgical success was 93 out of 106 (87.7%): 13 out of 94 (13.8%) failed by bulge symptoms, 2 out of 78 (2.6%) by prolapse beyond the hymen, 1 out of 85 (1.2%) by retreatment with pessary, and 0 by retreatment with surgery. There were no serious adverse events. Conclusion(s): The rate of incident mesh exposure between 1 and 3.9 years post-surgery was low, success rates remained high, and there were no delayed serious adverse events.Copyright © 2022, The International Urogynecological Association.

Matulonis, U., et al. (2023). "Final overall survival and long-term safety in the ENGOT-OV16/NOVA phase III trial of niraparib in patients with recurrent ovarian cancer (LBA 6)." Gynecologic Oncology 176(Supplement 1): S31-S32.
	Objectives: Primary results from the ENGOT-OV16/NOVA study showed that niraparib (nir) maintenance therapy (MT) significantly prolonged progression-free survival (PFS) in patients (pts) with platinum-sensitive recurrent ovarian cancer (PSROC) regardless of germline BRCA mutation (gBRCAm) or homologous recombination deficiency (HRD) biomarker status (median follow up 16.9 months). Previously reported long-term analyses on PFS2 indicated the benefit of nir MT beyond the first progression (median follow-up =67 months), but overall survival (OS) analyses were limited by missing data (Matulonis et al. Gynecol Oncol. 2021;162[suppl 1]: S24-S25). Recent data retrieval efforts reduced missing survival status from 17% to =2%, and the data cutoff was extended by 6 months. Here we report the final OS and long-term safety results in the updated dataset. Method(s): NOVA was a randomized, double-blind, placebo (PBO)-controlled phase III trial. Pts with PSROC were enrolled into independent gBRCAm and non-gBRCAm cohorts. Pts were randomized 2:1 to nir 300 mg once daily or PBO with stratification by PFS after penultimate platinum therapy (6 to <12 months vs >=12 months), the best response to the last platinum-based therapy (complete/partial), and prior bevacizumab (yes/no). The primary endpoint, PFS, was assessed by a blinded independent central review. OS was a secondary endpoint. For the updated analysis, a vital status procedure was completed to retrieve the last known alive status for 92 pts. with missing survival data (data cutoff Mar 31, 2021). Final OS was evaluated in both cohorts and by non-gBRCAm HRD status. Result(s): A total of 553 pts. were randomized. Median follow-up at data cutoff was >75 months across both cohorts and treatment arms. Survival status was available for 97.6% of pts. (540/553). Overall, OS maturity was 77.9%. Median OS was 40.9 months with nir and 38.1 months with PBO in the gBRCAm cohort (HR: 0.85; 95% CI: 0.61-1.20) and 31.0 and 34.8 months, respectively, in the non-gBRCAm cohort (HR: 1.06; 95% CI: 0.81-1.37). OS by HRD status is shown in the Table. No new safety signals were detected. Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was reported in 14/367 pts. (3.8%; 10 [7.4%] gBRCAm, 4 [1.7%] non-gBRCAm) who received nir versus 3/179 (1.7%; 2 [3.1%] gBRCAm, 1 [0.9%] non-gBRCAm) PBO pts. There was no evidence suggesting that toxicity, including hematologic events, MDS/AML, or cardiovascular events, contributed to the OS results. Conclusion(s): After a comprehensive effort to reduce missing data, we provide an updated, exploratory analysis of NOVA long-term follow-up data. The differences in OS between treatment arms were not interpreted to be significant in either cohort, though the OS hazard ratio numerically favored nir in the gBRCAm cohort. NOVA was not powered to show OS, and analyses were confounded by imbalances in post-progression therapy (including subsequent PARP inhibitors) by the treatment arm in both the gBRCAm and non-gBRCAm cohorts, including the exploratory HRD status subgroups. No new safety signals were observed with long-term follow-up. [Formula presented]Copyright © 2023

Matulonis Ursula, A., et al. (2022). "Patient reported outcomes for cisplatin and radiation followed by carboplatin/paclitaxel versus carboplatin/paclitaxel for locally advanced endometrial carcinoma: An NRG oncology study." Gynecologic Oncology 164(2): 428-436.
	Introduction: Chemotherapy plus radiation (Cis-RT + CP) did not demonstrate superiority in prolonging relapse-free survival compared to chemotherapy alone in patients with stage III or IVA endometrial carcinoma. The impact of treatment on quality of life (QOL), neurotoxicity (NTX) and psychometric properties of the gastrointestinal (GI) symptoms subscale during treatment and up to 1 year are described herein.; Methods: QOL assessments were scheduled at baseline, 6 weeks (post completion of RT (Cis-RT + CP) or prior to cycle 3 (CP)), then 18 weeks (end of treatment) and 70 weeks (1 year after the end of treatment) after starting treatment. QOL instruments included the FACT-En TOI, FACT/GOG-neurotoxicity (Ntx) subscale (short), and the gastrointestinal (GI) symptoms subscale.; Results: At the end of treatment, patients receiving Cis-RT + CP reported a statistically significant decreased QOL when compared to CP. The decline in QOL was reflected in physical well-being, functional well-being, and endometrial cancer specific concerns, but the minimally important differences (MID) were not considered clinically meaningful. Patients in both groups reported increased chemotherapy-induced Ntx symptoms with the CP group having worse scores and reaching peak symptoms at the time of chemotherapy completion. Patients on Cis-RT + CP reported statistically significantly worse GI symptoms after radiation therapy compared to patients on CP, this occurred across assessment intervals, though the MID was not meaningful. Psychometric evaluations indicated that the GI symptom scale is reliable, valid, and responsive to change.; Conclusions: PROs indicate that the chemoradiotherapy group experienced worse HRQoL and GI toxicity compared to patients randomized to chemotherapy alone for locally advanced endometrial cancer though based on the MID, these were not clinically meaningful differences. The GI symptom subscale was a reliable and valid scale that has value for future trials.; Trial Registration: NCT00942357.; Competing Interests: Declaration of Competing Interest Dr. Matulonis reports receiving consulting fees received from Merck, Novartis, Blueprint Medicine and Next Cure as well as participating on a Data Safety Monitoring Board or Advisory Board for Symphogen and Advaxis. Ms. Helen Huang, Dr. Marcus Randall, Dr. Paul DiSilvestro, Dr. Fowler, Dr. Powell, Dr. Dr. Spirtos, Dr. Tewari, Dr. Nakayama, Dr. Mutch have no conflicts of interest to disclose. Dr. Virginia L. Filiaci reports receiving support for the present manuscript from NCTN and NCORP SDMC grant funding from the NIH/NCI. She also reports grants from GOG Foundation, Inc. for contracts with institution for clinical trial work and NCI/NIH for IOTN, BIQSFP, MP2PRT and miscellaneous other subcontracts. Dr. Filiaci also reports receiving support for attending IDMC meeting from VBL Therapeutics as well as participating on Advisory Board for Tesaro. Monitoring Board. Dr. Katherine Moxley reports P20 grant to University of Oklahoma for Drug Resistance Core from the NIH as well as support for travel to attend NRG Oncology 2019 Winter and Summer meetings. Additionally, Dr. Moxley reports serving in a Leadership role for the SGO Program Committee. Dr. David Miller reports grants received from EMD Serono Research and Development Institute to him as well as grants to his Institution from the following entities: US Biotest, Advenchen Laboratories, Tesaro, Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, Merck Sharp & Dohme, AstraZeneca, Millenium Pharmaceuticals, Aprea AB, Regeneron, NVision, Leap Therapeutics, Novartis, Syros Pharmaceuticals, Karyopharm Therapeutics, Agenus and Akesobio. Dr. Miller also personally received consulting fees from the following: Genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Alexion Pharmaceuticals, Karyopharm Therapeutics, Incyte, Guardant Health, Janssen, Alexion Pharmaceuticals, Clovis Oncology, Asymmetric Therapeutics, LLC, Boston Biomedical Research I stitute, Tarveda Therapeutics, Myriad Genetic Laboratories Inc., GlaxoSmithKline LLC, AbbVie Inc., Incyte, EMD Serono Inc. and Seager Inc. as well as consulting fees paid to his Institution from Merck Sharp & Dohme. Dr. Miller also received honoraria from Clovis Oncology and Genentech. He also reports participating on an Advisory Board for Incyte. Dr. Lari Wenzel reports serving as Co-Chair of the NRG Oncology PCOR Committee. Dr. Daniela Matei reports NCI NRG Support grant received. Due to his unfortunate passing before publication, no statement is available for Dr. William Richards. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Matulonis Ursula, A., et al. (2023). "Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(13): 2436-2445.
	Purpose: Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor α (FRα). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC.; Methods: SORAYA enrolled FRα-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point.; Results: One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively.; Conclusion: MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.

Mauck, C., et al. (2023). "Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial." Clinical therapeutics 45(5): 415-425.
	Purpose: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV).; Methods: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability. Subjects were evaluated at screening, days 7 to 14 (Day 7-14), and days 21 to 30 (test-of-cure [TOC]). An acceptability questionnaire with 9 questions was administered at the Day 7-14 visit, and a subset of questions (#7-#9) was asked again at the TOC visit. At Visit 1, subjects were provided with a daily electronic diary (e-Diary) to collect information regarding study drug administration, vaginal discharge, odor, itching, and any other treatments used. Study site staff reviewed e-Diaries at the Day 7-14 and TOC visits.; Findings: A total of 307 women with BV were randomized to treatment (204 to the clindamycin gel group and 103 to the placebo gel group). Most (88.3%) reported at least one previously diagnosed BV episode, and more than one half (55.4%) had experience with other vaginal treatments for BV. At the TOC visit, almost all (91.1%) of the clindamycin gel subjects described their overall experience with the study drug as "satisfied" or "very satisfied," 95.8% indicated that they would be "likely" or "very likely" to use the product again if it became available after the study and they had BV again, and 93.7% would be "likely" or "very likely" to recommend their treatment to a friend who had BV. Almost all (90.2%) clindamycin-treated subjects responded that application was "clean" or "fairly clean," as opposed to "neither clean nor messy," "fairly messy," or "messy." Although 55.4% experienced leakage in the days after application, only 26.9% of those indicated that it was bothersome. Subjects receiving clindamycin gel also reported improvement in both odor and discharge, commencing shortly after dosing and continuing through the assessment period, regardless of whether they met the critical cure criteria.; Implications: A single dose of a new bioadhesive 2% clindamycin vaginal gel showed rapid resolution of symptoms and was highly acceptable as a treatment for bacterial vaginosis.; Clinicaltrials: gov identifier: NCT04370548.; Competing Interests: DECLARATION OF INTEREST Daré designed the study and managed the contract research organization that contracted with the sites, collected the data, and performed the analysis. Daré personnel were involved in data interpretation, writing the manuscript, and submitting the manuscript for publication. On March 31, 2022, Daré Bioscience, Inc and Organon & Co entered into an exclusive license agreement in which Organon obtained exclusive worldwide rights to develop, manufacture, and commercialize XACIATO (2% clindamycin phosphate vaginal gel). (Copyright © 2023. Published by Elsevier Inc.)

Mauck, C., et al. (2022). "Safety, Tolerability and Usability of Oral Estradiol (E2) and Progesterone (P4) versus Two Formulations of Dare HRT1, an Intravaginal Ring containing Bioidentical E2 and P4, in a First-In-Woman Phase I Study." Menopause 29(12): 1487-1488.
	Objective: DARE-HRT1 is an ethylene vinyl acetate (EVA) co-polymer monthly intravaginal ring (IVR) of bioidentical 17beta estradiol (E2) and progesterone (P4), being developed for treatment of moderate-to-severe vasomotor symptoms (VMS) with or without symptomatic vulvo-vaginal atrophy (VVA). Design(s): Dare HRT1-001 was a first-in-woman study of 28d treatment: 80 mug/d E2 + 4 mg/d P4 (IVR1) vs. 160 mug/d E2 + 8 mg/d P4 (IVR2) vs. oral E2 1 mg/d + oral P4 100 mg/d (ORAL). Participants completed a daily diary to record treatment emergent adverse events (TEAEs). At the end of treatment, IVR users completed an acceptability questionnaire. Result(s): Enrolled participants (n=34) were randomized to use IVR1 (n=10), IVR2 (n=12) or ORAL (n=12). Three participants were withdrawn from the study: two IVR2 users for unrelated TEAEs and one ORAL user for exclusionary pre-treatment laboratory criteria, thus 31 participants (IVR1=10, IVR2=10, ORAL=11) completed the study. Table 1 demonstrates that the TEAE profile of the IVRs were generally similar to the referent ORAL regimen. TEAEs were determined to be related to study product use more commonly with IVR2. However, one of the 12 IVR2 participants accounted for 26 of 47 reported TEAEs in that group. Endometrial biopsies were not performed routinely unless an endometrial stripe was >4 mm or for clinically significant postmenopausal bleeding (PMB). One IVR1 participant had an endometrial stripe increase from 4 mm at screening to 8 mm at end of treatment. Her endometrial histology was benign. Two other endometrial biopsies were also performed during the study for PMB and were benign. There were no clinically meaningful laboratory or vital sign abnormalities or trends identified in observed values or changes from baseline. Pelvic speculum examination identified no clinically significant abnormalities in any participant at any visit. Usability data are reported in Table 2, demonstrating both IVRs were highly acceptable. Conclusion(s): Both DAREHRT1 IVRs, E2 80 mug/d + P4 4 mg/d (IVR1) and E2 160 mug/d + P4 8 mg/d (IVR2) were safe and well-tolerated in healthy postmenopausal women. TEAE profiles were comparable to the referent marketed ORAL regimen.

Mayadev, J., et al. (2023). "A randomized prospective trial investigating patient reported satisfaction and knowledge with the use of a gynecologic brachytherapy educational video (1126)." Gynecologic Oncology 176(Supplement 1): S93-S94.
	Objectives: Gynecologic brachytherapy (BT) is a highly technical and critical component of radiation treatment for gynecologic cancers. Patient understanding of this complex procedure may vary, and the subsequent patient-reported outcomes in distress and treatment-specific satisfaction are lacking. This prospective randomized trial investigated patient-reported outcomes after an internet-based gynecologic brachytherapy video intervention. Secondary outcomes included patient and supportive caregiver views and feasibility. Method(s): Patients receiving gynecologic BT were prospectively randomized to Arm A: standard education; or Arm B: video education. Arm B patients had unlimited access to view the 16-min BT video via the internet (https://vimeo.com/403385455/d0716e3cc8). Patients' family members and friends were also provided access to the video. The NCCN Distress tool was used, and a treatment satisfaction survey was administered at baseline during the consult (1), first (2), and last (3) BT. Result(s): Between February 10, 2020, and January 28, 2022, 80 patients with gynecologic cancer were enrolled and randomized to receive standard education in arm A (n = 40) or video in arm B (n = 40). All patients completed the entire prescribed BT. In Arm B, 19/40 (48%) viewed the video, with 17/19 (89%) watching >50% of the video, with 10/40 (25%) friends and family views. Fifty-seven patients completed all 3 timepoints on the survey and analysis performed: arm A included 29 patients and arm B 28 patients. The median age of the cohort was 57 years (range: 26-89 years), non-Hispanic White (43.9%), or Hispanic (21.1%). Patients had cervical (54.4%) or uterine cancer (40.4%) and received EBRT (84.2%); 36.8% of the patients received cylinder BT, and 63.2% received intracavitary, hybrid, or interstitial BT. None of the sociodemographic, clinical, or treatment variables differed between groups A and B. Distress scores (scored from 0 to 10, with 0 being "no distress") were 4.31 (+/-3.26) versus 3.93 (+/-3.11) at 1, 4.59 (+/-3.01) versus 4.63 (+/-2.72) at 2, and 3.90 (+/-3.58) versus 3.22 (+/-2.94) at 3 timepoints, for arms A and B, respectively, with no statistically significant difference between arms (P = 0.65). There was no statistically significant difference in change of distress between surveys at the various timepoints on unadjusted analysis or multivariable analysis. Receipt of 5 BT (beta -6.55, 95% CI: -11.86 - -1.23, P = 0.02) compared to receipt of 4 was the only variable significantly associated with a decrease in distress score between surveys 1 and 3. For the satisfaction score, between arms A and B, there was no statistically significant difference in change of satisfaction between timepoint surveys (P = 0.94) on unadjusted or multivariate analysis. Vaginal cancer (beta -16.50, 95% CI: -31.74 - -1.25, P = 0.04) compared to cervical cancer was the only variable significantly associated with a decrease in satisfaction score between surveys 1 and 3. Conclusion(s): Gynecologic brachytherapy is a complex procedure with high technicality. Our data show that if offered an educational video intervention, <50% actually viewed the video. Using a BT-specific video did not impact distress or treatment-related satisfaction, as patients had relatively low distress scores and high satisfaction at all three timepoints. Further work is needed for impactful methods to increase BT knowledge that would translate into patient-reported distress and satisfaction increases.Copyright © 2023

Mayadev, J., et al. (2022). "Durvalumab in Combination with Chemoradiotherapy (CRT) in Locally Advanced Cervical Cancer (LACC): Radiotherapy (RT) Delivery and Subgroup Analyses from CALLA." International journal of radiation oncology biology physics 114(5): 1058-1059.
	Purpose/Objective(s): Concurrent platinum-based CRT has been standard of care in LACC for 20+ years. Simultaneously, RT techniques/technology have advanced, providing opportunity for improved treatment outcomes. In LACC, global standardization is critical to enhance RT quality and brachytherapy (BT) utilization. CALLA was the first global, placebo-controlled, Phase 3 study evaluating durvalumab (D), in combination with and following CRT, in LACC. We examine RT technological approaches, quality assurance measures, and related RT-based findings from CALLA. Materials/Methods: Newly diagnosed, untreated patients (pts) with high-risk LACC (FIGO 2009 IB2-IIB node positive, IIIA-IVA any node status) were randomized 1:1 to D (1500 mg IV) or placebo (P) Q4W (total <=24 doses), in combination with and following CRT. CRT comprised concurrent weekly IV platinum agent with external beam radiotherapy (EBRT) and BT. Detailed EBRT/BT protocol guidelines were included to ensure regional alignment. Prior to site qualification, a feasibility questionnaire and credentialing process confirmed compliance. A global RT subcommittee reviewed RT quality/compliance and created a scoring system to identify plan variations and potential clinical significance. RT quality was evaluated for each pt, including detailed review of contouring, EBRT plan dose/metrics, BT utilization/quality, RT completion, and treatment plan dose/quality variations. Result(s): A total of 770 women (105 sites,15 countries; 44% Hispanic, 39% Asian) were randomized. The primary endpoint of PFS was not met (hazard ratio [95% CI] for D+CRT vs P+CRT: 0.84 [0.65-1.08]; P=0.174). PFS at 12 and 24 months for D+CRT vs P+CRT were 76.0% vs 73.3% and 65.9% vs 62.1%, respectively. EBRT and BT were completed per protocol in 96.4% and 94.3% of pts for D+CRT and 98.4% and 95.3% for P+CRT. RT was delivered in <=59 days in 72.2% and 72.5% for D+CRT and P+CRT, respectively. Intensity-modulated RT was used for 86.8% (D+CRT) and 88.1% (P+CRT) of pts. A majority of pts received volume-directed BT (59.7% D+CRT, 63.3% P+CRT), and 87.4% and 88.1% of BT was high-dose rate. In both arms, median RT dose delivered was 5400 cGy and median equivalent dose was 8387.0 cGy (median BT dose/fraction 700 cGy, 4 fractions) (RT doses omit Japan). Clinically significant unacceptable variations in RT delivery were low; <25% of unacceptable variations were clinically significant. PFS by RT subgroups were generally aligned with the ITT population. Conclusion(s): CALLA integrated an exceptional quality assurance/control strategy to ensure global protocol compliance, showing high-quality RT delivery is achievable with high compliance. Although D+CRT did not significantly improve PFS vs P+CRT, CALLA illustrates the importance of strong multidisciplinary collaboration for optimal CRT delivery in high-risk LACC. Funding(s): AstraZenecaCopyright © 2022

Mayadev, J., et al. (2022). "Safety and immunogenicity of Anti PD-L1 (Atezolizumab) given as an immune primer or concurrently with extended field chemoradiotherapy for node positive locally advanced cervical cancer: an NRG Oncology trial (024)." Gynecologic Oncology 166(Supplement 1): S18-S19.
	Objectives: Immunotherapy added to standard chemoradiation (CRT) seeks to improve outcomes for patients with node-positive cervical cancer. Optimal sequencing of CRT with immunotherapy is unknown. NRG GY-17 (NCT03738228) is a randomized phase I/Ib trial of the anti-PD-L1 antibody, atezolizumab, before and concurrent (Arm A) or concurrent with CRT (Arm B) to determine the best sequence of therapy to result in immune activation, as determined by clonal expansion of T Cell Receptor Beta (TCRB) repertoires and tumor-associated T cell clones in peripheral blood. Secondary objectives included toxicity and the predictive value of T cell repertoire parameters for clinical outcomes. Method(s): A total of 40 patients were randomized; 36 patients with locally advanced cervical cancer with positive lymph nodes were randomized to three doses of atezolizumab (1200mg) on day -21, 0, 21 (Arm A) versus day 0, 21, 42 (Arm B). All eligible patients for analysis received CRT and >=1 dose of atezolizumab. Tumor biopsies were obtained prior to and during therapy, and peripheral blood was collected. T cell repertoire metrics were evaluated by Adaptive immunoSEQ assay. Dose-limiting toxicities were assessed during and up to 30 days post CRT. Comparison of arms and pre- to post-treatment comparisons were performed using Wilcoxon rank-sum or signed-rank test. Correlations of T cell clonality and diversity with clinical outcomes and biopsy results were explored. Result(s): Of the 40 patients, four patients were not assigned study treatment and were excluded from the analysis. For the 36 eligible and treated patients, the median follow-up time was 20 months. The median age was 48 years; most of the patients were non-Hispanic White and White and had performance status of 0, squamous cell carcinoma, and FIGO stage IIB. Seventy-five percent of all patients completed all protocol therapy, 86% received >4 cycles of cisplatin with RT. Of the 36 patients, 30 were DLT evaluable according to the protocol: Arm A: 16 patients with no DLTs; Arm B: 14 patients with three patients reported to have a DLT (8%): one immune-related event as colitis (3%), non-immune-related colitis, and thrombocytopenia with cisplatin delay?>2 wks. Overall, three patients in Arm A and seven patients in Arm B experienced a grade 3 or higher treatment-related adverse event; except one, all grade 3 events were deemed non-immune-related. Thirty-one patients had on-treatment tumor biopsy at the first brachytherapy; ten patients (28%) showed no residual tumor on biopsy. There was an increase in peripheral blood TCR clonal expansion and expansion of tumor-associated T cell clones between baseline and day 21 in Arm A (p=0.0001) and Arm B (p=0.001). There was no statistically significant difference between the two treatment arms for either T cell clonal expansion or expansion of tumor-associated T cell clones. Patients with higher pre-treatment TCR diversity had an increased likelihood of complete pathologic response in on-treatment biopsy (p= 0.049). Overall, at 12 months, the DFS for the entire cohort is 72%. Conclusion(s): Our data indicate that atezolizumab as a primer and concurrent with CRT is safe and shows immune-modulating activity in women with locally advanced cervical cancer. There was no difference in change in T cell clonality between the arms. Favorable DFS was observed in both arms at 12 months for this high-risk patient population. Correlation between the treatment schedule, T cell repertoire parameters, and clinical outcomes will be performed as the follow-up becomes more mature.Copyright © 2022 Elsevier Inc.

Mazandaran University of, M. and Sciences (2021). "Evaluation of the Effectiveness of Hypnotherapy on Pain Intensity in Endometriosis Patients Treated With Dinogest: A Randomized Controlled clinical trial." Iranian Registry of Clinical Trials.
	
Mazandaran University of, M. and Sciences (2023). "The effect of online brief mindfulness-based counseling on infertility related distress in infertile women under treatment: A randomized controlled clinical trial." Iranian Registry of Clinical Trials.
	
Mazandaran University of, M. and Sciences (2023). "Evaluation of the Effects of Traditional Dosage form Called Hamol-e-Aftimone in Improving Pelvic Pain, Quality Of Life And Ovarian Cyst Size in Endometriosis Patients; A Double-Blind, Placebo-Controlled Clinical Trial." Iranian Registry of Clinical Trials.
	
Mazzola, R., et al. (2019). "Modern radiotherapy in cancer treatment during pregnancy." Critical Reviews in Oncology/Hematology 136: 13-19.
	Breast cancer, gynecological malignancies and lymphomas are the most frequently diagnosed tumors in pregnant women. The feasibility of radiotherapy during pregnancy remains a subject of debate and clinicians continue to hesitate on this approach, trying to avoid radiotherapy in most cases. Since the 1990s, several technological advances, including intensity modulated and image guided radiation delivery, have been implemented in radiation oncology to improve the radiation treatment in terms of effectiveness and tolerability. It remains uncertain which short- and long-term health effects the radiation exposure of the fetus may have through advanced radiotherapy techniques. The present systematic literature review aims to summarize the limited current evidences of the feasibility and clinical results of "modern" radiotherapy procedures for the treatment of the most frequently diagnosed tumors in pregnant women. (Copyright © 2019 Elsevier B.V. All rights reserved.)

McCabe, J. E., et al. (2021). "Listening Visits for maternal depression: a meta-analysis." Archives of Women's Mental Health 24(4): 595-603.
	Listening Visits are a non-directive counseling intervention delivered by nurses to depressed postpartum women. In 2007, Listening Visits were listed as a recommended treatment in British national guidelines. They were removed from the guideline update, due to the small effect size drawn from a meta-analysis of five clinical trials with depressed and non-depressed postpartum women. The purpose of this meta-analysis is to provide an estimate of the true population effect of Listening Visits as a treatment for maternal depression compared to control conditions. A meta-analytic review was conducted of studies published before October 2020. Inclusion criteria required that the study was a pragmatic or randomized trial of Listening Visits delivered by non-mental health specialists to mothers with elevated symptoms of maternal depression. Post-treatment depression rates for the treatment and control groups were extracted from eligible studies. Six studies met eligibility criteria which included 703 participants. Analyses of observed effect sizes corrected for study artifacts revealed an estimate of 0.66 (95% CI: 0.32, 0.99) with high heterogeneity (Q = 17.95, p = 0.003, I2 = 72.14). After removing outliers and addressing heterogeneity across observed effect sizes, the meta-analytic estimate across four methodologically similar studies and 651 participants was 0.43 (95% CI: 0.24, 0.62). The moderate effect size for Listening Visits, considered together with the advantages afforded by how, where, and who provides this treatment, supports Listening Visits as a first-line intervention in a stepped care approach for mothers with mild to moderately severe depression symptoms.Copyright © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, AT part of Springer Nature.

McCammon, K., et al. (2021). "Early and Consistent Improvements in Urinary Symptoms and Quality of Life With OnabotulinumtoxinA in Patients With Overactive Bladder and Urinary Incontinence: results From a Randomized, Placebo-controlled, Phase IV Clinical Trial." Female Pelvic Medicine & Reconstructive Surgery 27(7): 450‐456.
	OBJECTIVES: This randomized, multicenter, placebo‐controlled, phase IV study assessed the efficacy and tolerability of onabotulinumtoxinA in patients with overactive bladder. METHODS: Patients were randomized 1:1 to onabotulinumtoxinA 100 U or placebo. Assessments over 12 weeks included: change from baseline in urinary incontinence (UI) episodes/day; proportions of patients who achieved 100% and 50% or greater reductions in UI episodes/day; proportion of patients using no incontinence pads in the previous 24 hours; and changes from baseline in micturition frequency, nocturia, urgency UI, Incontinence‐Quality of Life, King's Health Questionnaire, International Consultation on Incontinence Questionnaire‐UI Short Form scores and time to request retreatment. RESULTS: Significant reductions in UI episodes/day were seen with onabotulinumtoxinA versus placebo within week 1 posttreatment (‐2.9 vs ‐2.0, P = 0.005) through week 12 (coprimary endpoint: ‐3.5 vs ‐1.6, P < 0.001). Significantly more onabotulinumtoxinA‐treated patients achieved 100% (coprimary endpoint) and 50% or greater reductions in UI episodes/day. Decreases in other urinary symptoms were also seen within 1 week with onabotulinumtoxinA that continued through at least week 12. More onabotulinumtoxinA‐treated versus placebo‐treated patients required no incontinence pads at weeks 1 to 12, and greater improvements in quality of life measurements were seen. Time to request retreatment was significantly longer with onabotulinumtoxinA versus placebo (30.0 weeks vs 13.1 weeks; P < 0.001). No unexpected safety signals were observed. Urinary tract infection was the most commonly observed adverse event. CONCLUSIONS: Urinary symptom and quality of life improvements were observed with onabotulinumtoxinA within 1 week of treatment and were sustained for at least 12 weeks.

McCann, L. D., et al. (2023). "Pre-Operative Tamsulosin before Minimally Invasive Hysterectomy and Time to Spontaneous Void: A Randomized Controlled Trial." Journal of Minimally Invasive Gynecology 30(11 Supplement): S25-S26.
	Study Objective: The primary objective of this study is to determine the efficacy of tamsulosin in decreasing the postoperative time to void in women undergoing hysterectomy for benign conditions. The secondary objective is to determine if tamsulosin decreases the time to discharge compared to placebo. Design(s): The study was a double-blind, randomized controlled trial that took place at two campuses of a tertiary care hospital between June 2021 and January 2023. Approval from the institutional review board and registration on ClinicalTrials.gov were obtained prior to enrollment. Demographics, medical and surgical history, surgical details, blood pressure, surgery start and end times, PACU discharge times, and adverse events were recorded. Randomization was performed by the hospital pharmacy and participants received one dose of tamsulosin or placebo preoperatively. All patients underwent a voiding trial before PACU discharge. Setting(s): Preoperative setting and post-anesthesia care unit Patients or Participants: Participants undergoing minimally invasive hysterectomy were screened and excluded if they had a history of bladder cancer, plan for concurrent pelvic organ prolapse surgical repair, or medical contraindications to tamsulosin. Of 150 participants, 77 received tamsulosin and 73 received placebo. Intervention(s): Study participants were randomized to receive one dose of tamsulosin 0.4mg or placebo preoperatively. Measurements and Main Results: The group that received tamsulosin as a preoperative prophylactic dose was shown to have to a decreased, although not statistically significant, time to discharge as compared to the placebo group (2.4 hours vs. 2.6 hours, respectively, p=0.40). Time to spontaneous void was not statistically different between the tamsulosin or placebo groups (1.6 hours vs. 1.4 hours, respectively, p=0.60). The urinary retention rate was similar in both groups (n=2 in each cohort). Conclusion(s): The results suggest that the use of a single preoperative dose of tamsulosin does not lead to a significant decrease in postoperative time to void or time to discharge.Copyright © 2023

McCann, S. E., et al. (2021). "Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry." Nutrients 13(3).
	Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed 10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity (p < 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., Klebsiella, Lactobacillus, Slackia, Senegalimassilia) were unique to each group. Bacteria (e.g., Fusobacteria, Pyramidobacter and Odoribacter) previously associated with colorectal cancer and cardiovascular disease, both diet‐related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.

McCarthy, A., et al. (2021). "Neoadjuvant therapy or upfront surgery in advanced endometrial cancer: a systematic review protocol." BMJ Open 11(11): e054004.
	Introduction: There is no consensus on the optimal treatment strategy for people with advanced endometrial cancer. Neoadjuvant therapies such as chemotherapy and radiotherapy have been employed to try to reduce the morbidity of surgery, improve its feasibility and/or improve functional performance in people considered unfit for primary surgery. The objective of this review is to assess whether neoadjuvant chemotherapy or radiotherapy improves health outcomes in people with advanced endometrial cancer when compared with upfront surgery.; Methods and Analysis: This review will consider both randomised and non-randomised studies that compare health outcomes associated with the neoadjuvant therapy and upfront surgery in advanced endometrial cancer. Potential studies for inclusion will be collated from electronic searches of OVID Medline, Embase, international trial registries and conference abstract lists. Data collection and extraction will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodological quality of the studies will be assessed using the Risk of Bias 2 and Risk of Bias in Non-randomised Studies of Interventions tools. If appropriate, we will perform a meta-analysis and provide summary statistics for each outcome.; Ethics and Dissemination: Ethics approval was not required for this study. Once complete, we will publish our findings in peer-reviewed publications, via conference presentations and to update relevant practice guidelines.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

McCausland, V. and A. McCausland (2023). "Risk of Hysterectomy After Endometrial Ablation: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 142(5): 1262.
	Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest.

McCloskey Rebecca, J. and R. Reno (2019). "Complementary health approaches for postpartum depression: A systematic review." Social Work in Mental Health 17(1): 106-128.
	Postpartum Depression (PPD) affects approximately 9 - 20% of women. Many women with PPD go undiagnosed and/ or do not follow through on referrals for treatment. Although the most routinely prescribed treatments for PPD are antidepressant medication and psychotherapy, a significant number of women desire non-traditional options. This article provides a systematic review of ten recently published, randomized clinical trials in the examination of the effectiveness of complementary health approaches—the use of non-mainstream products and interventions—on PPD. A search of nine databases of the English language literature from the years 2006 to 2018 was performed. Review criteria included published work, utilization of randomized-controlled trials, and the use of a reliable and valid measurement tool to identify cases of PPD and monitor changes in symptom severity. The studies reviewed focused on the following interventions: aromatherapy, bright light therapy, electroacupuncture, infant massage, iron supplementation, mindfulness training, omega-3 fatty acids, saffron, and yoga. Outcomes demonstrate the feasibility and safety of these approaches, as well as varying degrees of effectiveness. While many were pilot studies using small sample sizes, the results are encouraging and substantiate the need for additional trials. Studies are summarized and limitations and implications for social work and future research are described.

McCloy, K., et al. (2022). "Evaluating the effectiveness of mindfulness alone compared to exercise and mindfulness on fatigue in women with gynaecology cancer (GEMS): Protocol for a randomised feasibility trial." MedRxiv.
	Background In 2020 Globocan reported nearly 1.4 million new cases of gynaecology cancer worldwide. Cancer related fatigue has been identified as a symptom that can be present for gynaecology cancer patients many years after treatment. The current evidence around the management of this symptom suggests that exercise has the most positive outcome. However, some ambiguity remains around the evidence and whether it can address all areas of fatigue effectively. More recently, other interventions such as mindfulness have begun to show a favourable response to the management of symptoms for cancer patients. To date there has been little research that explores the feasibility of using both these interventions together in a gynaecology cancer population. This study aims to explore the feasibility of delivering an intervention that involves mindfulness and mindfulness and exercise and will explore the effect of this on fatigue, sleep, mood and quality of life. Methods/Design This randomised control trial will assess the interventions outcomes using a pre and post design and will also include a qualitative process evaluation. Participants will be randomised into one of 2 groups. One group will undertake mindfulness only and the other group will complete exercise and mindfulness. Both groups will use a mobile application to complete these interventions over 8 weeks. The mobile app will be tailored to reflect the group the participants have drawn during randomisation. Self-reported questionnaire data will be assessed at baseline prior to commencing intervention and at post intervention. Feasibility will be assessed through recruitment, adherence, retention and attrition. Acceptability and participant perspective of participation (process evaluation), will be explored using focus groups. Discussion This trial will hope to evidence and demonstrate that combination of two interventions such as mindfulness and exercise will further improve outcomes of fatigue and wellbeing in gynaecology cancer. The results of this study will be used to assess (i) the feasibility to deliver this type of intervention to this population of cancer patients using a digital platform; (ii) assist this group of women diagnosed with cancer to manage fatigue and other symptoms of sleep, mood and impact their quality of life.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

McClure, C., et al. (2022). "Safety and tolerability of Pau d' Arco ( Tabebuia avellanedae) for primary dysmenorrhea: A single-arm, open-label trial on adults ages 18-45." Advances in integrative medicine 9(3): 159-166.
	Objectives: To evaluate the safety and tolerability of encapsulated Tabebuia avellanedae in generally healthy women aged 18-45 with primary dysmenorrhea.; Methods: A single arm, open-label trial was conducted in which 1050 mg/day of encapsulated Tabebuia avellanedae (Pau d'Arco) was administered to twelve healthy women aged 18-45 for eight weeks. The primary outcome was safety and tolerability as measured by standardized adverse events scales and serial collection of laboratory markers to assess general health, prothrombin times, and the presence or absence of anemia. Secondary outcomes included pain intensity, quality of life, and pain interference measured by the Visual Analog Scale (VAS), the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 survey, and the PROMIS Visual Sexual Function and Satisfaction: Interfering Factors survey, respectively. Exploratory outcomes included serum concentration of high-sensitivity C-reactive protein as a marker of systemic inflammation.; Results: Seventy-five percent of participants (n = 9/12) completed the study. Seventy-five percent of study participants (n = 9/12) reported an adverse event, most of which were characterized as mild, and none were determined to be a Food and Drug Administration (FDA) serious adverse event. Most laboratory markers stayed within normal limits throughout the study period with a few clinically mild abnormalities. There was a significant decrease in pain intensity compared to baseline after the first dose (p < .01), after 4 weeks of treatment (p < .01), and after 8 weeks of treatment (p < .01). Over the 8-week intervention period, pain interference, quality of life, and sexual function and satisfaction scores improved nonsignificantly and hs-CRP decreased nonsignificantly.; Conclusions: Tabebuia avellanedae supplementation of 1050 mg/day dose for eight weeks in generally healthy women aged 18-45 with primary dysmenorrhea was generally safe, associated with moderate tolerability, and associated with significant improvements in pain intensity scores. Future studies examining the safety and efficacy of Tabebuia avellanedae on primary dysmenorrhea are warranted.; Competing Interests: Declaration of conflicting interests None.

McConnell, M. A., et al. (2022). "Effect of an Intensive Nurse Home Visiting Program on Adverse Birth Outcomes in a Medicaid-Eligible Population: a Randomized Clinical Trial." JAMA 328(1): 27‐37.
	Importance: Improving birth outcomes for low‐income mothers is a public health priority. Intensive nurse home visiting has been proposed as an intervention to improve these outcomes. Objective: To determine the effect of an intensive nurse home visiting program on a composite outcome of preterm birth, low birth weight, small for gestational age, or perinatal mortality. Design, Setting, and Participants: This was a randomized clinical trial that included 5670 Medicaid‐eligible, nulliparous pregnant individuals at less than 28 weeks' gestation, enrolled between April 1, 2016, and March 17, 2020, with follow‐up through February 2021. Interventions: Participants were randomized 2:1 to Nurse Family Partnership program (n = 3806) or control (n = 1864). The program is an established model of nurse home visiting; regular visits begin prenatally and continue through 2 postnatal years. Nurses provide education, assessments, and goal‐setting related to prenatal health, child health and development, and maternal life course. The control group received usual care services and a list of community resources. Neither staff nor participants were blinded to intervention group. Main Outcomes and Measures: There were 3 primary outcomes. This article reports on a composite of adverse birth outcomes: preterm birth, low birth weight, small for gestational age, or perinatal mortality based on vital records, Medicaid claims, and hospital discharge records through February 2021. The other primary outcomes of interbirth intervals of less than 21 months and major injury or concern for abuse or neglect in the child's first 24 months have not yet completed measurement. There were 54 secondary outcomes; those related to maternal and newborn health that have completed measurement included all elements of the composite plus birth weight, gestational length, large for gestational age, extremely preterm, very low birth weight, overnight neonatal intensive care unit admission, severe maternal morbidity, and cesarean delivery. Results: Among 5670 participants enrolled, 4966 (3319 intervention; 1647 control) were analyzed for the primary maternal and neonatal health outcome (median age, 21 years [1.2% non‐Hispanic Asian, Indigenous, or Native Hawaiian and Pacific Islander; 5.7% Hispanic; 55.2% non‐Hispanic Black; 34.8% non‐Hispanic White; and 3.0% more than 1 race reported [non‐Hispanic]). The incidence of the composite adverse birth outcome was 26.9% in the intervention group and 26.1% in the control group (adjusted between‐group difference, 0.5% [95% CI, ‐2.1% to 3.1%]). Outcomes for the intervention group were not significantly better for any of the maternal and newborn health primary or secondary outcomes in the overall sample or in either of the prespecified subgroups. Conclusions and Relevance: In this South Carolina‐based trial of Medicaid‐eligible pregnant individuals, assignment to participate in an intensive nurse home visiting program did not significantly reduce the incidence of a composite of adverse birth outcomes. Evaluation of the overall effectiveness of this program is incomplete, pending assessment of early childhood and birth spacing outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03360539.

McCormack, L., et al. (2023). "Immediate versus delayed urinary catheter removal following non-hysterectomy benign gynaecological laparoscopy: a randomised trial." BJOG : an international journal of obstetrics and gynaecology 130(9): 1112-1119.
	OBJECTIVE: To compare rates of urinary retention and postoperative urinary tract infection between women with immediate versus women with delayed removal of indwelling catheter following benign non-hysterectomy gynaecological laparoscopic surgery. DESIGN: This randomised clinical trial was conducted between February 2012 and December 2019, with follow-up to 6 weeks. SETTING: Two university-affiliated teaching hospitals in Sydney, Australia. POPULATION: Study participants were 693 women aged 18 years or over, undergoing non-hysterectomy laparoscopy for benign gynaecological conditions, excluding pelvic floor or concomitant bowel surgery. METHODS: Three hundred and fifty-five participants were randomised to immediate removal of urinary catheter and 338 participants were randomised to delayed removal of urinary catheter. MAIN OUTCOME MEASURES: The co-primary outcomes were urinary retention and urinary tract infection. Secondary outcomes included hospital readmission, analgesia requirements, duration of hospitalisation and validated bladder function questionnaires. RESULTS: Urinary retention was higher after immediate compared with delayed removal of the urinary catheter (8.2% vs 4.2%, RR 1.8, 95% CI 1.0-3.0, p = 0.04). Although urinary tract infection was 7.2% following delayed removal of the urinary catheter and 4.7% following immediate removal of the urinary catheter, the difference was not statistically significant (RR 0.7, 95% CI 0.3-1.2, p = 0.2). CONCLUSIONS: There is an increased risk of urinary retention with the immediate compared with the delayed removal of the urinary catheter following benign non-hysterectomy gynaecological laparoscopic surgery. The difference in urinary tract infection was not significant. There is 1/12 risk of re-catheterisation after immediate urinary catheter removal. It is important to ensure that patients report normal voiding and emptying prior to discharge, to reduce the need for readmission for the management of urinary retention.

McCormack, M., et al. (2023). "LBA8 A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancer: The GCIG INTERLACE trial." Annals of Oncology 34(Supplement 2): S1276.
	Background: Locally advanced cervical cancer (LACC) is treated with chemoradiation (CRT). However, many patients relapse and die from metastatic disease. A feasibility study demonstrated a good response rate to short course weekly induction chemotherapy (IC) delivered before standard CRT and the INTERLACE trial investigated whether this approach improves both progression free survival (PFS) and overall survival (OS). Method(s): Women with squamous, adeno or adenosquamous carcinoma FIGO (2008) stage IB1 node positive,IB2,II,IIIB, IVA were eligible. Patients were randomised (1:1) to receive either CRT alone (5 cycles weekly cisplatin) or IC (6 weeks carboplatin AUC2 and paclitaxel 80mg/m2) followed by the same CRT in week 7. Mandated minimum total EQD2 dose 78Gy to Point A with 3D brachytherapy recommended. All centres underwent radiation quality assurance. Primary endpoints were PFS (target hazard ratio [HR] 0.65) and OS (target HR 0.65-0.70). Result(s): 500 patients were recruited from 32 centres in 5 countries (Nov 2012-Nov 2022). Median age 46 (range 24-78) years. Stage distribution was: IB1/2; 9%, II;77%, IIIB;11% and IVA;3%. 57% were node negative and 82% squamous subtype. Arms were balanced. 92% of IC patients had 5/6 cycles carboplatin/paclitaxel. Median interval from IC to CRT was 7 days. 84% (IC/CRT) vs. 89% (CRT alone) had 4/5 cycles cisplatin. In the CRT arm 92% and 89% completed external beam and brachytherapy respectively; corresponding figures in the IC/CRT arm were 97% and 95%. The median overall treatment time for CRT was 45 days in both arms. Grade >=3 adverse events were seen in 59% (IC/CRT) vs. 48% (CRT alone). Median follow up 64 months. 5 year PFS rate is 73% with IC/CRT and 64% with CRT alone (HR 0.65; 95%CI:0.46-0.91, p=0.013). The corresponding 5-year OS rates are 80% and 72% (HR 0.61:95%CI:0.40-0.91, p=0.04). Conclusion(s): Induction chemotherapy followed by CRT significantly improves PFS and OS in LACC and should be considered a new standard of care. INTERLACE recruited patients from diverse health care settings demonstrating that IC followed by CRT is feasible in all countries. Clinical trial identification: EudraCT: 2011-001300-35. Legal entity responsible for the study: Trial Sponsor: University College London Trial Sponsor reference: UCL 11/0034. Funding(s): Cancer Research UK. Disclosure: M. McCormack: Other, Personal, Advisory Board: GSK, Eisai, AstraZeneca; Other, Personal and Institutional, Coordinating PI: Roche. L. Farrelly: Financial Interests, Institutional, Other, Research Grant, Institutional, Financial interest, Grant for a UCL-academic sponsored clinical trial: MSD, AstraZeneca, Autolus, Boehringer Ingelheim, GRAIL Inc, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Other, Takeda: Janssen; Financial Interests, Institutional, Other, Research Grant for commercially sponsored trial through the ENGOT Network: Clovis, Seagen, Immunogen, GSK, Novartis, Aravive. C. Kent: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen; Financial Interests, Personal, Advisory Board: Clovis; Non-Financial Interests, Personal, Leadership Role, trustee of prostaid Charity: Prostaid Charity. E. Hudson: Financial Interests, Personal, Other, Advisory boards, lecture fees and travel: GSK/Tesaro, Clovis; Financial Interests, Personal, Other, Advisory boards, s and travel: Roche. T. Mathews: Non-Financial Interests, Personal, Leadership Role, NIHR gynae subspeciality lead for gynae research for South/West Yorkshire and Humber side: NIHR. J. Forrest: Non-Financial Interests, Personal, Other, Trsutee FORCE cancer support charity: FORCE cancer support charity; Financial Interests, Institutional, Other, PI EngotCx 11 Trial: Marke Sharpe & Dohme; Financial Interests, Institutional, Other, PI Engot Cx 12 Tria: Seagan. R. Bhana: Financial Interests, Personal, Other, All related to sponsorships for conferences, meetings and courses and market research or teaching sponsorshipAll related to sponsorships for conferences, meetings and courses and market research or teaching spo sorship: Pfizer; Financial Interests, Personal, Other, All related to sponsorships for conferences, meetings and courses and market research or teaching sponsorship: Astellas, Novartis, MSD, Jannsen, Takeda, Eisai, BMS, Clovis, AstraZeneca, GSK, Boston scientific, Palette Life Sciences, Varian, EUSA pharma. H. Stobart: Non-Financial Interests, Personal, Membership or affiliation: Independent Cancer Patients' Voice. A. Mukhopadhyay: Other, Personal, Other, Honoraria for being DSMB member 2023: Canariabio; Financial Interests, Personal, Licencing Fees or royalty for IP, Royalty payment one off in 2019 through Newcastle University: Clovis Oncology; Financial Interests, Institutional, Funding, esearch funding to KolGoTrg for conducting the HPV screening study PRECERCA 2023: Cepheid Global; Non-Financial Interests, Personal, Leadership Role, Project lead- PRECERCA study ( prevention of cervical cancer) - POint of care HPV testing for tea garden workers in Himalayan foothills: N/A; Non-Financial Interests, Personal, Leadership Role, Director: Kolkata Gynecoloy Oncology Trials and Translational Research Group. A.M. Hacker: Financial Interests, Institutional, Other, Research Grant, Institutional, Financial interest, Grant for a UCL-academic sponsored clinical trial: MSD, AstraZeneca, Autolus, Boehringer Ingelheim, GRAIL Inc, Jannsen, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Other, Research Grant for commercially sponsored trial through the ENGOT Network: Clovis, Seagen, Immunogen, GSK, Novartis, Aravive. A. Hackshaw: Financial Interests, Personal, Advisory Board, AH is an investigator for an academic study (SUMMIT) sponsored by UCL that is funded by GRAIL, Inc.; has received one honorarium for an advisory board meeting for GRAIL, Inc; received a consulting fee from Evidera Inc (for one GRAIL-initiated project).: GRAIL Inc; Financial Interests, Personal, Other, For delivering general education/training in clinical trials.: AbbVie, Boehringer Ingelheim, Clovis, Ipsen, Takeda, AstraZeneca, Daiichi Sankyo, Merck Serono, MSD, UCB, Kyowa Kirin, Servier, Sobi, Pfizer, Roche; Financial Interests, Personal, Stocks/Shares, Shares were sold in 2020: Illumina, Thermo Fisher; Financial Interests, Institutional, Research Grant, Grant for a UCL-academic sponsored clinical trial: Roche, MSD, Autolus, AstraZeneca, Boehringer Ingelheim, GRAIL Inc, Takeda, Pfizer, Novartis, Bristol Myers Squibb, Janssen; Non-Financial Interests, Principal Investigator, Co-lead academic investigator for an observational study sponsored and conducted by Roche. Unpaid/no honoraria for this role.: Roche; Non-Financial Interests, Advisory Role, AH is on the scientific advisory board for Adela Bio and receives no payments/honoraria for this but has share options available.: Adela Bio; Non-Financial Interests, Advisory Role, Unpaid member of advisory board: Navio. J.A. Ledermann: Financial Interests, Personal, Advisory Board, Advisory Board and Speaker Fees: AstraZeneca, Clovis Oncology, GSK; Financial Interests, Personal, Advisory Board: Artios Pharma, Eisai, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Ellipses, Immunogen, Miltenyi, Novocure, Immagene; Financial Interests, Personal, Invited Speaker, Speaker Fees: Neopharm; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Mersana; Financial Interests, Personal, Other, IDMC: Sutro Bio, Mersana; Financial Interests, Institutional, Research Grant, Clinical Research University: AstraZeneca, MSD/Merck; Non-Financial Interests, Leadership Role, Vice President ( 2019-2021): European Society of Gynaecological Oncology; Non-Financial Interests, Officer, Chair Gynaecological Clinical Practice Guidelines: ESMO; Other, Associate Editor: Therapeutic Advances in Medical Oncology: Sage Publishing. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

McCormick, C. A., et al. (2020). "Managing vasomotor symptoms effectively without hormones." Climacteric : the journal of the International Menopause Society 23(6): 532-538.
	Vasomotor symptoms (hot flushes and/or night sweats) affect approximately 80% of women over the menopause transition and can affect quality of life, productivity, and relationships. Vasomotor symptoms are the main reason for seeking treatment during the menopausal transition. Although menopausal hormone therapy (MHT) is effective for symptom management, the majority of symptomatic women do not take MHT. In this article, we review the evidence for non-hormonal treatments for vasomotor symptoms, including pharmacological and non-pharmacological approaches, and provide a clinical algorithm for managing symptomatic women.

McCoy, J. A., et al. (2023). "Efficacy of Propranolol to Reduce Cesarean Delivery in Prolonged Labor: A Randomized Controlled Trial." Obstetrics and Gynecology 142(1): 71-79.
	OBJECTIVE:To evaluate the rates of cesarean delivery in patients with prolonged labor randomized to receive intravenous (IV) propranolol compared with placebo. METHOD(S):A double-blind, placebo-controlled, randomized trial was conducted at two hospitals within a large academic health system. Eligible patients were at 36 weeks or more with a singleton gestation and prolonged labor, defined as: 1) prolonged latent phase of labor (dilation less than 6 cm after 8 hours or more with ruptured membranes and receiving oxytocin infusion) or 2) prolonged active phase of labor (dilation 6 cm or greater and less than 1-cm cervical dilation change over 2 hours or more with ruptured membranes and receiving oxytocin infusion). Patients were excluded for severe preeclampsia, maternal heart rate less than 70 beats per minute, maternal blood pressure less than 90/50 mm Hg, asthma, diabetes requiring insulin during labor, or a cardiac contraindication to beta-blockade. Patients were randomized to propranolol (2 mg IV) compared with placebo (2 mL normal saline IV), with one possible repeat dose. The primary outcome was cesarean delivery; secondary outcomes included labor duration, shoulder dystocia, and maternal and neonatal morbidity. With an estimated cesarean delivery rate of 45%, alpha 0.05, and 80% power, we required 163 patients per group to detect a 15% absolute reduction in cesarean delivery rate. A planned interim analysis was performed, and the trial was stopped for futility. RESULT(S):From July 2020 to June 2022, 349 patients were eligible and approached; 164 were enrolled and randomized, with 84 in the propranolol group and 80 in the placebo group. The rate of cesarean delivery was not different between groups (57.1% propranolol vs 57.5% placebo, relative risk [RR] 0.99, 95% CI 0.76-1.29). Results were similar by subgroup of prolonged latent (n=123) and active (n=41) phases of labor and nulliparous (n=137) and multiparous (n=27) patients. Though not statistically significant, the frequency of postpartum hemorrhage was higher in the propranolol group (20% vs 10%, RR 2.02, 95% CI 0.93-4.43). CONCLUSION(S):In this multisite, double-blind, placebo-controlled randomized trial, there was no difference in cesarean delivery rate for patients who received propranolol compared with those who received placebo for management of prolonged labor.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

McDonald, S. M., et al. (2022). "Influence of prenatal exercise on the relationship between maternal overweight and obesity and select delivery outcomes." Scientific Reports 12(1): 17343.
	Women with overweight or obesity (OWOB) have an increased risk of cesarean birth, preterm birth (PTB), and high birth weight infants. Although regular exercise decreases this risk in healthy weight women, these associations have not been explored in OWOB. Women were randomized at 13‐16 weeks' gestation to 150‐min of moderate‐intensity exercise (n = 131) or non‐exercising control (n = 61). Delivery mode, gestational age (GA), and birth weight (BW) were obtained via electronic health records. Pregnant exercisers had no differences in risk of cesarean birth, PTB, or BW compared to control participants. OWOB exercisers had higher rates of cesarean birth (27.1% vs. 11.1%), trends of higher PTB (15.3% vs. 5.6%), but normal weight babies relative to normal weight exercisers. Controlling for race and body mass index (BMI), maternal exercise reduced the relative risk (RR) for cesarean birth from 1.63 to 1.43. Cesarean births predicted by pre‐pregnancy BMI and fitness level, whereas BW was predicted by race, gestational weight gain (GWG), pre‐pregnancy fitness level, and exercise level. Cesarean birth was predicted by pre‐pregnancy BMI and fitness level, while maternal exercise reduced the magnitudes of the relative risks of cesarean birth. Maternal exercise, pre‐pregnancy fitness level, and GWG predict neonatal BW.Trial Registration: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics‐#NCT03838146, 12/02/2019, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=Edit&listmode=Edit&uid=U0003Z0X&ts=8&sid=S0008FWJ&cx=77ud1i .

McDonald, V., et al. (2022). "Laparoscopic guided liposomal bupivacaine injection compared to transversus abdominus plane block for postoperative pain after robotic gynecologic oncology surgery." Gynecologic Oncology 166(3): 432-437.
	Objective: The purpose of this study was to determine if laparoscopically guided transversus abdominis plane block (Lap-Tap) with liposomal bupivacaine provides superior postoperative pain control when compared to ultrasound-guided block (US-Tap) with liposomal bupivacaine at the time of robotic surgery for gynecology oncology patients.; Methods: This was a prospective randomized controlled trial assigning patients to one of two cohorts: Cohort 1 consisted of US-Tap administered before the procedure using liposomal bupivacaine, Cohort 2 consisted of Lap-Tap administration with laparoscopic visualization using the medication above. Primary outcomes were pain scores and total opioid use in Oral Morphine Equivalents (OME) during the first 72 h after surgery. Secondary outcomes were postoperative pain satisfaction and oral narcotic requirements.; Results: There was a significant increase in oral narcotic use in the first 24 h in the US-Tap cohort compared to the Lap-Tap cohort: Lap-Tap mean = 6.73 ± 8.22 OME versus US-Tap mean = 12.69 ± 12.94 p = 0.018 OME. The increase was equivalent to one additional Hydrocodone-Acetaminophen 7.5 mg/325 mg in the first 24 h after surgery. However, total oral narcotic use over the first 72 h was not significantly different between the two cohorts: Lap-Tap mean = 21.73 ± 19.83 OME, US-Tap mean = 32.50 ± 29.47, p = 0.062 OME. In addition, there was no significant difference in satisfaction or pain scores between the US-Tap and Lap-Tap groups at 24, 48, or 72-hours.; Conclusions: Lap-Taps are comparable to US-Tap for postoperative analgesia during the first 72-h after surgery when performing robotic-assisted gynecologic oncology surgery.; Competing Interests: Declaration of Competing Interest All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert-testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. (Copyright © 2022 Elsevier Inc. All rights reserved.)

McDowell, M., et al. (2022). Comparing Postoperative Pain After Vessel Sealing Device Versus Conventional Suturing Methods for Vaginal Hysterectomy and Pelvic Reconstructive Surgery.
	No Results Available Device: LigaSureTM vessel sealing device Postoperative Pain|Vaginal Pain|Abdominal Pain Female Not Applicable 100 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 21-094 April 1, 2024

McLaren, S., et al. (2023). "Investigating the Role of 17beta-Estradiol on the Serotonergic System, Targeting Soy Isoflavones as a Strategy to Reduce Menopausal Depression: A Mechanistic Review." Journal of the American Nutrition Association.
	Low serotonin is one factor implicated in the development of depression. 17beta-estradiol (E2) has been shown to modulate gene expression regulating the neurotransmission of serotonin. Sex hormone levels fluctuate dramatically during the menopausal transition, coinciding with a 14-fold increased risk of depression. This review aimed to examine the effect of soy isoflavones to support decreased and variable E2 levels before and after menopause, linked to an investigation of the pathophysiological mechanisms underlying the protective influence of E2 on the serotonin pathway. The overall aim of this review is to assess the potential of soy isoflavones to reduce depression in middle-aged women. A systematic literature search was performed in three stages. 1,421 papers were screened for relevance to the research aims and objectives. 63 papers were selected based on pre-defined inclusion/exclusion criteria (13 reviews, 24 mechanistic and 26 intervention studies) and critically appraised. Available research supported the hypotheses that E2 increases serotonin synthesis and availability through stimulation of tryptophan hydroxylase-2 (TPH-2) and decreased degradation by monoamine oxidase-A (MAO-A). There was less scientific agreement on the effects of E2 on serotonin transporter (SERT) and serotonin receptors 1 A and 2 A. Studies varied widely on the effectiveness of soy isoflavones in reducing depressive symptoms in (peri)menopausal women. Animal and human studies acknowledge women's increased risk of depression linked to fluctuating E2 rather than absolute levels. However, mechanisms linking E2 variability with depression remain an underrepresented area of research. Study limitations and heterogeneity may contribute to varying results for soy isoflavones and some effects of E2 on the serotonin pathway.Copyright © 2023 American Nutrition Association.

McLaughlin Hannah, D., et al. (2023). "Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer." Gynecologic Oncology 178: 89-95.
	Objective: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis.; Methods: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models.; Results: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53).; Conclusion: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events. (Copyright © 2023 Elsevier Inc. All rights reserved.)

McLaughlin Pamela, M. J., et al. (2022). "Maintenance Therapy with Aromatase Inhibitor in epithelial Ovarian Cancer (MATAO): study protocol of a randomized double-blinded placebo-controlled multi-center phase III Trial." BMC Cancer 22(1): 508.
	Background: A high percentage of epithelial ovarian cancers (EOC) express the estrogen receptor (ER), which is an ideal target for endocrine therapy. Letrozole is a proven, potent aromatase inhibitor, extensively tested and used in the treatment of ER positive breast cancer. In addition, it seems a potent drug for patients with heavily pre-treated OC as demonstrated in several distinctive settings. However, it has never been evaluated prospectively in a maintenance setting for ovarian cancer after standard of care. The here proposed trial aims to define a population of EOC patients, who would benefit from the effectiveness of the generic agent letrozole, with little expected toxicity and thus beneficial impact on overall quality of life (QoL).; Methods: In this international multicenter randomized, placebo-controlled phase III trial at clinical centers in Switzerland, Germany and Austria, we plan to include 540 patients with primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low- or high-grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer. Patients are randomized in a 1:1 ratio into two groups: receiving blinded study treatment (letrozole or placebo tablets). When assuming a HR of 0.7, a median PFS of 18 months in the control arm and a median PFS of 25.7 months in the treatment arm, a two-sided alpha level of 5%, 3.5 years recruitment and 1.5 years observation time, we expect 330 events to have occurred within these 5 years in the total cohort yielding a power of 90%. Follow-up data for the whole cohort will be collected for up to 10 years and for the low-grade cancer for up to 12 years.; Discussion: The here proposed randomized phase III trial aims to identify patients with EOC in the maintenance setting, who benefit from the effectiveness of the letrozole, by proving its efficacy whilst maintaining a high standard of QoL due to the limited toxicity expected in comparison to the current alternative drugs on the market for this treatment phase.; Trial Registration: This trial is registered at clinicaltrials.gov under the identifier NCT04111978 . Registered 02 October 2019. (© 2022. The Author(s).)

McNeil Candice, J., et al. (2022). "Evaluating the Efficacy of Eradicating Gardnerella vaginalis Vaginal Colonization With Amoxicillin: A Randomized, Double-Blind, Phase 2 Study." Sexually Transmitted Diseases 49(2): 133-138.
	Background: Research suggests that Gardnerella vaginalis (GV) is the keystone pathogen in bacterial vaginosis (BV). Knowledge gaps exist regarding the role of GV eradication in the development of BV. This study was designed to test the hypothesis that vaginal colonization with GV could be eradicated by treatment of women without BV with amoxicillin, a drug highly active against GV. If GV is necessary for the development of BV, then eradication of GV may prevent the development of BV.; Methods: We conducted a randomized control trial of amoxicillin 500 mg twice daily versus placebo for 7 days in women aged 18 to 45 years without vaginitis who screened positive for vaginal colonization with GV by quantitative polymerase chain reaction. Test-of-cure visit for GV was conducted at day 21.; Results: One hundred seventy-two women met preliminary criteria and were screened for enrollment. Ninety-seven GV-positive women were randomized to receive amoxicillin versus placebo. Eradication of GV occurred in 21% of women randomized to amoxicillin versus 16% on placebo (P = 0.757). In the 4 weeks between screening and test-of-cure visit, 16 of 92 (17%) of participants developed Nugent scores greater than 3 with 8 of 92 (9%) having BV. All of these were in participants in whom GV was not eradicated (P = 0.035).; Conclusions: The study failed to show a benefit of treatment with amoxicillin to eradicate GV. No participants in whom GV was eradicated had progression to abnormal vaginal flora during the study period.; Competing Interests: Conflict of Interest: None declared. (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Mecdi Kaydirak, M. and E. Aslan (2021). "Efficacy of nursing support in the pre- and postmedical termination of pregnancy phases: A randomized study." Omega: Journal of Death and Dying 84(1): 51-68.
	This study was conducted to evaluate the efficiency of a nursing support program developed in accordance with the Roy adaptation model that was applied in addition to routine nursing care during the treatment process of pregnant women for whom the medical termination decision. This study, which was conducted using a pretest-posttest design, was a prospective, single-blind, and randomized-controlled empirical study. In the experimental group, although the first and last assessment State Anxiety Inventory scores were higher than those in the control group after the medical termination nursing support program, there was no significant difference. Compared with the control group, there were positive differences in the Scale of Ways of Coping with Stress, Adaptation Assessment Form for Role Function Area, and physical complaints in the experimental group. At the follow-up assessment, the total Perinatal Grief Scale score was significantly higher than that in the control group. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Medical, A. B. P., et al. (2021). Evaluation of VagiVitalAC for Treatment of Candida Vulvovaginitis.
	No Results Available Device: VagiVitalAC Presence or not of candida fungi in the vaginal culture after 7 days treatment|Presence or not of candida fungi in the vaginal culture after 30 days treatment|For patients with initial treatment effect (i.e., no presence of candida fungi in the vaginal culture) after 7 days treatment, relapse at day 30, after continued treatment|Change in self-reported vulvovaginal symptoms (vaginal itching/burning and/or soreness and/or vaginal discharge and/or pain during sexual intercourse) after 7 days treatment compared to baseline (patient's own experience)|Change in self-reported vulvovaginal symptoms after 7 days treatment compared with baseline (patient's own experience), that has been self-identified by the patient as being the most bothersome to her|Change in self-reported vulvovaginal symptoms (vaginal itching/burning and/or soreness and/or vaginal discharge and/or pain during sexual intercourse) after 30 days treatment compared to baseline (patient's own experience)|Change in self-reported vulvovaginal symptoms after 30 days treatment (patient's own experience), that has been self-identified by the patient at baseline as being the most bothersome to her|Frequency of Adverse events Adverse Events (AEs)/Serious Adverse Events (SAEs)/Device Deficiencies (DDs)/Adverse Device Effects (ADEs)/Serious Adverse Device Effects (SADEs) at 7 days|Frequency of Adverse events AEs/SAEs/DDs/ADEs/SADEs at 30 days|Presence or not of candida fungi in the vaginal culture after 90 days treatment.|For patients with initial treatment effect by VagiVitalAC (i.e. no presence of candida fungi in the vaginal culture) after 7 and 30 days treatment, relapse at day 90, after continued treatment.|Change in self-reported vulvovaginal symptoms after 7 days treatment compared to baseline, Investigational device group compared to comparator group (patient's own experience).|Change in self-reported vulvovaginal symptoms after 7 days treatment, Investigational device group compared to comparator group (patient's own experience), that has been self-identified by the patient at baseline as being the most bothersome to her.|Change in self-reported vulvovaginal symptoms (vaginal itching/burning and/or soreness and/or vaginal discharge and/or pain during sexual intercourse) after 90 days treatment compared to baseline (patient's own experience).|Change in self-reported vulvovaginal symptoms after 90 days treatment (patient's own experience), that has been self-identified by the patient at baseline as being the most bothersome to her.|Frequency of Adverse events AEs/SAEs/DDs/ADEs/SADEs at 7 days, Investigational device group compared to comparator group|Frequency of Adverse events AEs/SAEs/DDs/ADEs/SADEs at 90 days. Female Not Applicable 126 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment VagiPep102|CIV-21-06-037087 June 2022

Medicine Physicians Committee for, R. (2022). Nutritional Intervention for Endometriosis.
	No Results Available Behavioral: Plant-based Intervention Group Modified Biberoglu and Behrman Scale: change from baseline|Endometriosis Health Profile (EHP-30): change from baseline|Inflammatory biomarkers: change from baseline|Body weight: change from baseline|Blood lipids: change from baseline|Estrogen levels: change from baseline|Gut microbiome composition: change from baseline|Biomarkers of endometriosis and inflammation: change from baseline Female Not Applicable 120 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Pro00059650 August 2025

Medicine Washington University School, o. and o. Health National Institutes (2023). Endometriosis Group Care.
	No Results Available Other: Peer Empowered Endometriosis Pain Support (PEEPS) Pain Interference|Physical Function|Sexual Function|Endometriosis-specific quality of life|Anxiety|Depression|Pain Catastrophizing|Overall symptom improvement|Modified every day discrimination scale Female Not Applicable 40 Other|NIH Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 202206202 January 2025 Brief Summary The goal of this clinical trial is to test the effectiveness of the Peer Empowered Endometriosis Pain Support (PEEPS) program in people living with endometriosis-related pelvic pain. The main question[s] it aims to answer are: Is PEEPS effective at decreasing pain interference and improving patient-reported quality of life outcomes? What are the barriers and facilitators to PEEPS implementation? Participants will engage in eight weekly 2-hour sessions led by an endometriosis specialist, pain psychologist, pelvic floor physical therapist, and yoga instructor. At these sessions they will participate in peer support, education, mindfulness, and yoga. Show less Detailed Description This is an 8 week interdisciplinary, integrative group care program conducted through the Department of Obstetrics and Gynecology (OB/GYN) at Washington University in St. Louis (WUSTL). The program, called PEEPS, incorporates mindfulness, physical therapy, yoga, physical activity, nutrition, and education. Additionally, PEEPS will provide peer support and demonstrate investment of individual clinicians and the healthcare system. The program focuses on equipping participants with pain management and coping skills so they have an expanded toolkit to manage their pain after completing the program.

Medicine Washington University School, o., et al. (2024). AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer.
	No Results Available Drug: Paclitaxel|Drug: Batiraxcept Frequency and severity of treatment-emergent adverse events|Serum sAXL and GAS6 ratio|Pharmacokinetic (PK) parameters (including Cmax) as determined from AVB-500 serum levels|Pharmacokinetic (PK) parameters (including Tmax) as determined from AVB-500 serum levels|Pharmacodynamic effects as determined by changes from baseline in serum GAS6 levels|Overall response rate (ORR)|Progression-free survival (PFS)|Recommended Phase 2 dose (RP2D) of AVB-500 in combination with paclitaxel|Incidence of anti-drug antibodies (ADA)|Overall survival (OS) Female Phase 1 36 Other|NIH|Industry Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 202306082 November 4, 2033

Medicine Washington University School, o., et al. (2024). Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer.
	No Results Available Drug: Telaglenastat|Radiation: Radiation treatment|Drug: Cisplatin Progression-free survival (PFS) - experimental arm only|Acute toxicity as measured by number of acute adverse events experienced by participant - experimental arm only|Late toxicity as measured by number of late adverse events experienced by participant - experimental arm only|Overall survival (OS) All Phase 2 42 Other|NIH|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 202301163|R01CA181745 July 7, 2030

Meernik, C., et al. (2023). "Outcomes after assisted reproductive technology in women with cancer: a systematic review and meta-analysis." Human reproduction (Oxford, England) 38(1): 30-45.
	Study Question: What are the associations between a history of cancer and outcomes after ART?; Summary Answer: Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART.; What Is Known Already: Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes.; Study Design, Size, Duration: We conducted a systematic review with meta-analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021.; Participants/materials, Setting, Methods: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-and-fill method to assess funnel plot asymmetry.; Main Results and the Role of Chance: Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage.; Limitations, Reasons for Caution: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes.; Wider Implications of the Findings: Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis.; Study Funding/competing Interest(s): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests.; Registration Number: N/A. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mehrnoush, V., et al. (2021). "Efficacy of the Complementary and Alternative Therapies for the Management of Psychological Symptoms of Menopause: A Systematic Review of Randomized Controlled Trials." Journal of Menopausal Medicine 27(3): 115-131.
	Menopause is not a high-risk period for psychiatric illness but can cause psychological issues; the most common of which are anxiety and depression, which can impair coping and reduce women's quality of life. Thus, many women have leaned toward complementary and alternative medicine (CAM) for the relief of menopause-related symptoms. No rigorous study exists in the literature on the effects of CAMs on the psychological symptoms of menopause despite this growing patient interest. This systematic review aimed to assess the efficacy of CAM interventions on psychological symptoms of menopause. Databases (PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar) were searched from January 2000 to May 2021 using the keywords: menopause, menopausal symptoms, psychological symptoms, and complementary and alternative medicine. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool (MMAT) for randomized clinical trials. Of the 704 articles found, 33 articles with 3,092 participants entered the final review. Aromatherapy, massage, yoga, and acupuncture, as well as some dietary and herbal supplements improved psychological symptoms during menopause based on the findings of the current study. However, the effectiveness of reflexology and exercise was debatable. However, necessary precautions should be taken when using them in clinical settings despite the positive effect of various CAM interventions on reducing psychological symptoms. More studies with a higher methodology quality are required to make better decisions about the effect of various CAM interventions on the psychological symptoms of menopause.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2021 by The Korean Society of Menopause.)

Mei, R., et al. (2022). "Mindfulness-Based Interventions for the Occurrence of Postpartum Depression in Elderly Primiparas." Contrast media & molecular imaging 2022: 4202676.
	This study aimed to investigate the independent risk factors for the occurrence of postpartum depression (PPD) in elderly primiparas and the effect of mindfulness-based intervention (MBI) on improving the PPD. Two hundred cases of elderly primiparas who underwent delivery in our hospital from January 2016 to December 2019 were enrolled as study participants and divided into an occurrence group ( n = 60) and a nonoccurrence group ( n = 140) according to whether they developed PPD. The occurrence group was divided into a study group ( n = 30) receiving MBI and a control group ( n = 30) without any intervention. Independent risk factors influencing the occurrence of PPD were identified using univariate and multivariate logistic regression analyses. The effect of the intervention was also analyzed in the study group. Education level, marital status, household monthly income per person, sex of the newborn, milk volume, sleep quality, and relationship with in-laws were risk factors for the development of PPD. After the intervention, Five Facet Mindfulness Questionnaire scores were increased in the study group and were higher than in the control group ( P < 0.05). The study group also exhibited higher 10-item Connor-Davidson Resilience Scale scores, lower Hamilton Depression Rating Scale and Schizophrenia Quality of Life Scale scores than the control group ( P < 0.05). A variety of independent risk factors affected the occurrence of PPD in elderly primiparas, and MBI should be targeted clinically to reduce their negative emotions, increase psychological resilience, and improve their quality of life.; Competing Interests: The authors declare that there are no conflicts of interest. (Copyright © 2022 Rui Mei et al.)

Mei, S., et al. (2022). "Mediterranean Diet Combined With a Low-Carbohydrate Dietary Pattern in the Treatment of Overweight Polycystic Ovary Syndrome Patients." Frontiers in Nutrition 9: 876620.
	Objectives: To determine the therapeutic effect of a Mediterranean diet (MED) combined with a low-carbohydrate (LC) dietary model in overweight polycystic ovary syndrome (PCOS) patients.; Methods: In this 12-week randomized controlled clinical trial, 72 overweight patients with PCOS were randomly assigned to one of two energy-restricted dietary models: the MED/LC diet or the Low fat (LF) diet. After the intervention, the number of the two groups returned to normal menstruation was counted. Body weight, body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), serum fasting insulin(FINS), fasting plasma glucose(FPG), insulin resistance index (HOMA-IR), quantitative insulin sensitivity index (QUIKI), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were compared between 2 groups before and after intervention.; Results: MED/LC group had more significant reduction trend in weight (-6.10 ± 1.52 kg vs -4.79 ± 0.97 kg, P < 0.05), BMI (-2.12 ± 0.57 kg/m 2 vs -1.78 ± 0.36 kg/m 2 , P < 0.05), WC (-6.12 ± 5.95 cm vs -3.90 ± 1.58 cm, P < 0.05), WHR (-0.06 ± 0.02 vs -0.03 ± 0.02, P < 0.05), BF% (-2.97% ± 1.78% vs -1.19% ± 0.91%, P < 0.05), TT (-0.20 ± 0.24 ng/mL vs 0.08 ± 0.11 ng/Ml, P < 0.001), LH (-5.28 ± 3.31 mIU/mL vs -3.39 ± 3.64 mIU/mL, P < 0.05), and LH/FSH (-1.18 ± 0.75 vs -0.66 ± 1.05, P < 0.05) compared with the LF group. In addition, FPG (0.05 ± 0.38 mmol/mL vs -0.50 ± 1.01 mmol/mL, P < 0.001), FINS (-4.88 ± 6.11 μU/mL vs -8.53 ± 5.61 μU/mL, P < 0.01), HOMA-IR index (-1.11 ± 1.51 vs -2.23 ± 0.25, P < 0.05), and QUIKI index (0.014 ± 0.016 vs 0.028 ± 0.019, P < 0.05) decreased significantly in the MED/LC group compared with the LF group. Comparing the changes in lipid parameters between the two groups (LF vs MED/LC), significant differences in TG (-0.33 ± 0.32 mmol vs -0.76 ± 0.97 mmol, P < 0.05), TC (-0.40 ± 1.00 mmol vs -1.45 ± 2.00 mmol, P < 0.05), and LDL-C (-0.41 ± 1.05 mmol vs -0.73 ± 0.76 mmol, P < 0.05) were observed.; Conclusion: The results of this study suggest that the MED/LC diet model is a good treatment for overweight PCOS patients, significantly restoring their menstrual cycle, improving their anthropometric parameters and correcting their disturbed endocrine levels, and its overall effectiveness is significantly better than the LF diet model. Therefore, this study recommends that the MED/LC diet model can be used in the clinical treatment of patients with overweight PCOS.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JQ declared a shared affiliation with the author JY to the handling editor at the time of review. (Copyright © 2022 Mei, Ding, Wang, Ni and Yu.)

Mei, Y., et al. (2024). "Preimplantation genetic testing for aneuploidy optimizes reproductive outcomes in recurrent reproductive failure: a systematic review." Frontiers in Medicine 11: 1233962.
	Introduction: Recurrent reproductive failure (RRF) is a common pregnancy complication, imposing great physical, emotional and financial burden for the suffered couples. The leading cause of RRF is believed to be aneuploid embryo, which could be solved by preimplantation genetic testing for aneuploidy (PGT-A) in theory. With molecular genetic development, PGT-A based on comprehensive chromosomal screening (CCS) procedures and blastocyst biopsy is widely applied in clinical practice. However, its effects in RRF were not defined yet. Method(s): A systematic bibliographical search was conducted without temporal limits up to June, 2023. Studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. Result(s): Twenty studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. It revealed that PGT-A could optimise the reproductive outcomes of RRF sufferers, especially in those with advanced age. However, in patients with multiple occurrences of pregnancy losses, the benefits of PGT-A were limited. Discussion(s): More randomized controlled trials with large sample size are required to evaluate the benefits of PGT-A in RRF sufferers and identify which population would benefit the most.Copyright © 2024 Mei, Lin, Chen, Zheng, Ke, Liang and Wang.

Meier, T. and o. Cincinnati University (2021). Adjuvant Hypofractionated Whole Pelvis Radiation Therapy in Endometrial Cancer.
	No Results Available Radiation: Hypofractionated WPRT Safety profile of hypofractionated, isoeffective whole pelvis radiation regimens for post-operative treatment of endometrial cancer using CTCAE version 5.0 and Patient Reported Outcome-CTCAE.|Maximum tolerated dose per fraction (MTDF) of hypofractionated, isoeffective whole pelvis radiation regimens for post-operative treatment of endometrial cancer through CTCAE data and gastrointestinal PRO-CTCAE data.|Impact of hypofractionated WPRT on patient quality of life using the Functional Assessment of Cancer Therapy-Endometrial version 4.0.|Patient compliance with hypofractionated WPRT, as defined by how many patients are able to complete WPRT without a break in treatment. Female Not Applicable 15 Other Allocation: N/A|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment UCCC-GYN-20-01 July 4, 2025

Meina, Y., et al. (2021). "Effects of vitamin D supplementation on ovulation and pregnancy in women with polycystic ovary syndrome: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Meirmanova, A., et al. (2023). "Surgical management of genital prolapse and combined gynecological pathologies in women: A meta-analysis." Electronic Journal of General Medicine 20(2): em446.
	Introduction: Prolapse can be fixed using a variety of surgical procedures. The goal of the present study was to examine the current literature on various surgical techniques for treating female genital organ prolapse. Method(s): The PubMed and Medline databases were explored for pertinent literature up through August 2022 for this meta-analysis. The terms [surgery] AND [management] AND [genital prolapse OR gynaecological diseases] AND [randomised control studies OR randomised control trials] were used as search criteria. The studies that met the inclusion criteria were considered qualified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Cochrane handbook of "Systematic reviews of interventions" was used for risk of bias assessment. Result(s): The investigations found significant difference in the heterogeneity between the groups with a 76% I2 value (p<0.00001). There was little variability among the six trials that examined robotic and laparoscopic therapy of prolapse (I2=0%, p=0.94). In six investigations, the odd ratio revealed no statistically significant difference between groups (1.05; 95% CI, 0.52, 2.12). However, generally there were no appreciable differences between robotic and laparoscopic treatment of female prolapse. There was a low-risk bias among the selected studies. Conclusion(s): According to this meta-analysis study, laparoscopic surgery performed better job of managing prolapse than abdominal surgery.Copyright © 2023 by Author/s and Licensed by Modestum. All rights reserved.

Meixuan, L., et al. (2023). "Acupuncture for menopausal hot flushes, an overview and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Mejia-Garcia, C. (2022). "Extraskeletical functions of vitamin D." Medicina Interna de Mexico 38(1): 75-84.
	BACKGROUND: Nowadays, the interest in vitamin D supplementation goes beyond its calcemic functions because deficiency in its concentrations has been related to immunological, gynecological and human reproductive diseases. OBJECTIVE(S): To review the most recent evidence in relation to the consequences of its deficiency in different alterations in the reproductive life of women and men. METHODOLOGY: Retrospective trial based on the bibliographic search of articles relating vitamin D deficiency with the appearance of polycystic ovary syndrome, uterine myomatosis, endometriosis, ovarian reserve, male factor (in reproduction), assisted reproduction techniques, pregnancy, lactation, and menopause. The search was performed in PubMed and Google Scholar databases for articles published between 1999 and 2020. RESULT(S): We found 108 articles and discarded 91 because they did not meet the inclusion criteria. Since the analysis was limited exclusively to the relationship of the appearance of diseases in women linked to alterations in reproductive life due to vitamin D deficiency, only 1 7 were analyzed. CONCLUSION(S): In clinical practice, making decisions about different treatments is always difficult, and even more so when there is controversy about when, how, and how much. In general, it seems effective and safe to take vitamin D with the high-dose schedule, since it increases adherence to treatment due to its convenience and does not represent a greater risk of toxicity; it also allows prompt correction of serum concentrations of the vitamin, especially in patients in whom it is desired to reach the objective in a short time, such as women who will undergo reproductive treatment.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Mejia-Gomez, J., et al. (2022). "Use of a vaginal CO 2 laser for the management of genitourinary syndrome of menopause in gynecological cancer survivors: a systematic review." Climacteric : the journal of the International Menopause Society 25(3): 228-234.
	Genitourinary syndrome of menopause (GSM) may arise from the hypoestrogenism caused by ovarian function destruction following gynecological cancer treatments. GSM may also be present in menopausal women and its symptoms might be exacerbated by cancer treatments. Historically, patients with hormone-dependent gynecological cancer and physicians have been less comfortable using vaginal estrogen due to fear of recurrence. CO 2 vaginal laser therapies have demonstrated efficacy as a non-hormonal alternative for GSM treatment in healthy menopausal patients. The objective of this study was to evaluate the data on the effect of a CO 2 vaginal laser for the management of GSM in gynecological cancer patients. Databases searched included MEDLINE, Embase, PubMed, Cochrane and Google Scholar. Selected studies assessed use of a CO 2 vaginal laser in gynecological cancer patients with GSM. A total of 269 studies were retrieved. Four studies met the inclusion criteria. Each study followed a different type of CO 2 vaginal laser protocol for the management of GSM in gynecological cancer patients. There are no randomized controlled trials that assess the use of a CO 2 vaginal laser in gynecologic cancer patients. The number of published gynecological cancer patients treated with a CO 2 laser for the management of GSM is extremely limited ( N < 100). There is a lack of literature on the impact and safety of vaginal CO 2 laser use to manage GSM in gynecologic cancer patients.

Mejia-Gomez, J., et al. (2021). "The impact of cannabis use on vasomotor symptoms, mood, insomnia and sexuality in perimenopausal and postmenopausal women: a systematic review." Climacteric : the journal of the International Menopause Society 24(6): 572-576.
	Objective: This study aimed to evaluate the published data on the effect of cannabis use in perimenopausal and postmenopausal women to alleviate menopausal symptoms, insomnia and anxiety.; Methods: Databases searched included Ovid MEDLINE, PubMed, Ovid Embase, Web of Science, Scopus, CINAHL, PsycINFO, Cochrane, LILACS and AMED. Selected studies assessed perimenopausal or postmenopausal women, cannabis use impact and menopausal symptoms.; Results: A total of 564 studies were retrieved. Three studies met the inclusion criteria. One study controlled for participant cannabis use and reported on the effects of cannabis and placebo cigarette smoking on mood in 10 postmenopausal women. Another study assessed associations between drug use with hot flashes and insomnia in 120 HIV-infected women and found that menopausal status and cannabis use was crudely associated with the presence of hot flashes. The last study evaluated expectancies of 115 menopausal patients who endorsed lifetime cannabis use and reported that women expected cannabis to improve depression, anxiety, hot flashes and problems with sleep. None of these studies assessed quality of life as an outcome.; Conclusion: There is a paucity of literature on the impact of cannabis use in menopause. Research into cannabis consumption in menopause is essential, as it is frequently used to alleviate symptoms without evidence of its benefits.

Mejia-Montilla, J., et al. (2022). "Vitamin D supplementation and inflammatory markers in women with polycystic ovary syndrome and vitamin D deficiency."  59(1): 53‐61.
	The aim of the study was to evaluate the effects of vitamin D supplementation on inflammation markers in women with polycystic ovary syndrome and vitamin D deficiency. A double‐blind, randomized, controlled, randomized clinical study was performed in patients with polycystic ovary syndrome attended at Hospital Central "Dr. Urquinaona", Venezuela in the period January 2014 to December 2020. Participants who were randomized to the study group (group A) received 5000 IU of cholecalciferol (vitamin D3) daily for 12 weeks. Group B was considered as control. Anthropometric variables, hormonal parameters, insulin resistance and inflammation markers (ultrasensitive C‐reactive protein, interleukin‐6 and tumor necrosis factor α) were measured. Eighty‐four women in group A and 85 women in group B were analyzed. No significant differences were found with respect to anthropometric variables, hormonal variables, insulin resistance and vitamin D concentrations (p=ns). When analyzing changes in inflammatory marker values, significant decreases in ultrasensitive C‐reactive protein, interleukin‐6 and tumor necrosis factor α concentrations were observed, associated with an increase in serum vitamin D concentrations (p<0.005) in group A. Group B showed no significant changes in these markers during the study (p=ns). It is concluded that vitamin D supplementation for 12 weeks in women with polycystic ovary syndrome and vitamin D deficiency results in a significant decrease in inflammatory markers concentrations.

Mejías-Gil, E., et al. (2021). "Kinesio Taping vs. Auricular Acupressure for the Personalised Treatment of Primary Dysmenorrhoea: A Pilot Randomized Controlled Trial." Journal of Personalized Medicine 11(8).
	BACKGROUND: Dysmenorrhoea is the medical term for menstrual pain. The World Health Organization estimates that up to 81% of women of childbearing age are affected by this condition, and it is one of the leading causes of absenteeism from work and school among women. Although there are pharmacological treatments available for menstrual-pain relief, they do not respond to all women's needs. Therefore, there is a need to study and develop non-pharmacological alternatives to broaden the individualised treatment options for dysmenorrhea. There are scarce studies published on non-pharmacological treatments, such as kinesio tape and auricular acupressure for the relief of menstrual pain, but the scientific evidence available suggest that these techniques may be beneficial in addressing this problem. The objective of this pilot study was to assess and compare the effectiveness of kinesio tape and auricular acupressure to decrease pain and drug intake in women with primary dysmenorrhoea. METHODS: This was a double-blind randomized clinical controlled trial. The period of study was from September 2017 to August 2018. Women enrolled in the University of Extremadura and who had primary dysmenorrhoea were randomized to five groups: control (n = 23), kinesio tape (n = 23), placebo kinesio tape (n = 23), auricular acupressure (n = 23) and placebo auricular acupressure (n = 22). Measures were taken during the pretreatment phase (at four menstrual cycles), during the post-intervention phase (at four menstrual cycles) and during the follow-up phase (at the first and third menstrual cycles after the treatment was completed). The primary outcome measures were mean pain intensity, maximum pain intensity, number of painful days and dose of drug intake during menstruation, measured with the Visual Analogue Scale. The secondary outcome measures were the length of the cycle, the length of menstruation, the drug intake and the type of drug. RESULTS: In all, 108 participants completed the study. The statistical analysis (MANOVA, ANOVA, t-paired and McNemar tests) showed that kinesio tape and auricular acupressure have a beneficial effect on pain relief (mean pain intensity, p < 0.001; maximum pain intensity, p < 0.001; number of painful days, p = 0.021; dose of drug intake, p < 0.001). In addition, once the treatments were withdrawn, the auricular-acupressure group maintained lower scores during the first follow-up cycle (p < 0.001). CONCLUSIONS: Kinesio tape and auricular acupressure decrease pain and drug intake in women with primary dysmenorrhoea. The changes in the auricular-acupressure group seemed to last longer. The results suggest that these techniques could be used as complementary personalised therapies to the pharmacological treatment and not as a substitution.

Mekdes Daba, F., et al. (2022). "Effectiveness, Safety and Acceptability of Second-trimester abortion by non-physician providers: A systematic review and planned meta-analysis."
	
Mekdes, W., et al. (2023). "Complications of second-trimester medical and surgical abortion."
	
Melo, P., et al. (2022). "Evidence for the effectiveness of immunologic therapies in women with subfertility and/or undergoing assisted reproduction." Fertility and Sterility 117(6): 1144-1159.
	Implantation is a critical step in the establishment of a successful pregnancy, depending on a complex immune-endocrine dialogue between the developing embryo and maternal endometrium. Research suggests that altered immunity in the maternal decidua results in implantation impairment and failure. Immunomodulatory drugs have, thus, been widely used in assisted conception to aid embryo implantation, despite an absence of consensus on their effectiveness and safety. We conducted a systematic review and meta-analysis of interventional studies investigating the use of immunomodulators in women undergoing assisted reproduction. Evidence was uncertain of an effect for most of the included interventions, owing to heterogeneous findings and a paucity of high-quality studies. For certain patient subgroups, however, the use of specific immunomodulatory therapies may offer some benefit. There is a need for further large randomized controlled trials to corroborate these findings.

Melo, P., et al. (2022). "The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET)." Human Reproduction Open 2022(4): hoac054.
	Study Question: What is the association between serum progesterone levels on the day of frozen embryo transfer (FET) and the probability of live birth in women undergoing different FET regimens?; Summary Answer: Overall, serum progesterone levels <7.8 ng/ml were associated with reduced odds of live birth, although the association between serum progesterone levels and the probability of live birth appeared to vary according to the route of progesterone administration.; What Is Known Already: Progesterone is essential for pregnancy success. A recent systematic review showed that in FET cycles using vaginal progesterone for endometrial preparation, lower serum progesterone levels (<10 ng/ml) were associated with a reduction in live birth rates and higher chance of miscarriage. However, there was uncertainty about the association between serum progesterone levels and treatment outcomes in natural cycle FET (NC-FET) and HRT-FET using non-vaginal routes of progesterone administration.; Study Design Size Duration: This was a multicentre (n = 8) prospective cohort study conducted in the UK between January 2020 and February 2021.; Participants/materials Setting Methods: We included women having NC-FET or HRT-FET treatment with progesterone administration by any available route. Women underwent venepuncture on the day of embryo transfer. Participants and clinical personnel were blinded to the serum progesterone levels. We conducted unadjusted and multivariable logistic regression analyses to investigate the association between serum progesterone levels on the day of FET and treatment outcomes according to the type of cycle and route of exogenous progesterone administration. Our primary outcome was the live birth rate per participant.; Main Results and the Role of Chance: We studied a total of 402 women. The mean (SD) serum progesterone level was 14.9 (7.5) ng/ml. Overall, the mean adjusted probability of live birth increased non-linearly from 37.6% (95% CI 26.3-48.9%) to 45.5% (95% CI 32.1-58.9%) as serum progesterone rose between the 10th (7.8 ng/ml) and 90th (24.0 ng/ml) centiles. In comparison to participants whose serum progesterone level was ≥7.8 ng/ml, those with lower progesterone (<7.8 ng/ml, 10th centile) experienced fewer live births (28.2% versus 40.0%, adjusted odds ratio [aOR] 0.41, 95% CI 0.18-0.91, P = 0.028), lower odds of clinical pregnancy (30.8% versus 45.1%, aOR 0.36, 95% CI 0.16-0.79, P = 0.011) and a trend towards increased odds of miscarriage (42.1% versus 28.7%, aOR 2.58, 95% CI 0.88-7.62, P = 0.086). In women receiving vaginal progesterone, the mean adjusted probability of live birth increased as serum progesterone levels rose, whereas women having exclusively subcutaneous progesterone experienced a reduction in the mean probability of live birth as progesterone levels rose beyond 16.3 ng/ml. The combination of vaginal and subcutaneous routes appeared to exert little impact upon the mean probability of live birth in relation to serum progesterone levels.; Limitations Reasons for Caution: The final sample size was smaller than originally planned, although our study was adequately powered to confidently identify a difference in live birth between optimal and inadequate progesterone levels. Furthermore, our cohort did not include women receiving oral or rectal progestogens.; Wider Implications of the Findings: Our results corroborate existing evidence suggesting that lower serum progesterone levels hinder FET success. However, the relationship between serum progesterone and the probability of live birth appears to be non-linear in women receiving exclusively subcutaneous progesterone, suggesting that in this subgroup of women, high serum progesterone may also be detrimental to treatment success.; Study Funding/competing Interests: This work was supported by CARE Fertility and a doctoral research fellowship (awarded to P.M.) by the Tommy's Charity and the University of Birmingham. M.J.P. is supported by the NIHR Birmingham Biomedical Research Centre. S.F. is a min r shareholder of CAR Fertility but has no financial or other interest with progesterone testing or manufacturing companies. P.L. reports personal fees from Pharmasure, outside the submitted work. G.P. reports personal fees from Besins Healthcare, outside the submitted work. M.W. reports personal fees from Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflict of interest to declare.; Trial Registration Number: ClinicalTrials.gov: NCT04170517. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Melo, V., et al. (2022). "Omega-3 supplementation in the treatment of polycystic ovary syndrome (PCOS) - a review of clinical trials and cohort." Endocrine regulations 56(1): 66-79.
	Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women associated with cardiovascular disease and obesity. The possible benefits of omega-3 supplementation in this syndrome have been discussed much. This study is aimed to verify, based on the scientific data published, if there are any benefits in the omega-3 supplementation in the treatment of PCOS and to indicate its possible dosages for the treatment of polycystic ovary. The work consists of a systematic review of clinical trials and cohort of the MEDLINE/PubMed database from 2009 to October 2019. All studies that analyzed the omega-3 supplementation in women with PCOS were included. Cross-sectional studies, review articles, systematic reviews, meta-analysis, duplicates, studies in animals or cell culture, studies with omega-3 supplementation via food or associated with other supplementations were not included, except those involving vitamin E. In total, 21 articles were selected. Despite the heterogeneity of the studies selected, indirect benefits were observed mainly regarding the glycemic profile, such as insulin resistance reduction, lipid profile modulation (i.e. decrease in total cholesterol, triglycerides, and elevation of high-density lipoprotein), and the regulation of the androgenic profile. As for the anthropometric profile, the studies were scarce and most of them had no significant meaning. Regarding the antioxidant profile and inflammatory biomarkers, the findings differ among studies, but promising results were observed with different doses over 12 weeks of use, such as C-reactive protein (CRP) reduction. Thus, omega-3 fatty acids promote indirect benefits in the treating of women with PCOS. However, to reveal well-defined standards for dosage and supplementation time, further studies are needed. (© 2022 Vitoria Melo et al., published by Sciendo.)

Melvin, E. M., et al. (2022). "A Comparison of Vaginal pH using Prasterone, Estradiol Cream or Non-hormonal Vaginal Moisturizer for Genitourinary Syndrome of Menopause (VpHresh)." International Urogynecology Journal 33(Supplement 2): S410.
	Introduction: Genitourinary Syndrome of Menopause (GSM) includes symptoms of vaginal irritation, dryness, dyspareunia, and recurrent urinary tract infections. Topical vaginal estrogen is considered the gold standard treatment for GSM, but alternative treatment modalities include prasterone and non-hormonal/over-the-counter vaginal moisturizers. Few studies compare these three treatment modalities for GSM. Objective(s): To compare the change in vaginal pH and Vaginal Health Index (VHI) scores in women with GSM using vaginal estradiol cream, prasterone suppositories, or OTC vaginal moisturizers at baseline and 12 weeks. Method(s): This is an ongoing observational pilot study comparing estrogen (1 g nightly for 2 weeks, then 0.5 g twice weekly), prasterone (6.5 mg suppository nightly), or OTC moisturizers (1 applicator every 3 days) for the treatment of GSM. Patients were recruited between 8/2020 - 11/2021 at a single academic practice. Eligible participants were postmenopausal females who were English- speaking and had GSM symptoms with a baseline vaginal pH >= 5. Women were excluded if they were on systemic or topical hormone therapy within 12 weeks of enrollment or on active endocrine therapy with either a selective estrogen receptor modulator or aromatase inhibitor. After provider counseling on treatment options for GSM, women chose their treatment arm and were followed for 12 weeks. At the baseline and 12 week visits, participants underwent genitourinary examination with vaginal pH measurement and clinically validated Vaginal Health Index (VHI) scoring. Student's t-test and Kruskall-Wallis rank sum test were used to compare continuous parametric and nonparametric variables, respectively. Fisher's exact test was used for categorical variables. Result(s): Of the 24 women who completed the study, 6 were in the estrogen arm, 9 in the prasterone arm and 9 in the OTC moisturizer arm. There were no significant differences in the baseline demographics (Table 1). The estrogen and prasterone treatment arms had significant reduction in pH from baseline to 8-12 weeks by 2.0 (SE=0.35, p value <0.0001) and 1.5 (SE=0.29, p <0.0001) respectively (Table 2a). There was no significant change in the pH value in the OTC moisturizer arm (p value = 0.1383). The mean VHI scores increased significantly from baseline for all treatment arms: in the estrogen arm, VHI scores improved by a mean of 13.8 points (SE=1.8, p<0.01); in the prasterone arm, VHI scores improved by a mean of 10.8 points (SE=1.5, P <0.01); in the OTC moisturizer arm, VHI scores improved by a mean of 3.7 points (SE=1.5, P =0.02) (Table 2b). Conclusion(s): Vaginal estradiol cream and prasterone suppositories significantly improved the vaginal pH of women with GSM over 12 weeks of therapy, while OTC moisturizers did not significantly alter vaginal pH. Similarly, VHI scores improved by a greater degree in the estradiol and prasterone treatment arms compared to the OTC moisturizer arm. These findings suggest estrogen cream and prasterone suppositories are both effective options for treating GSM, while OTC moisturizers are less effective.

Mendes, P. C. S., et al. (2023). "Effect of pelvic floor muscle training on reports of urinary incontinence in obese women undergoing a low-calorie diet before bariatric surgery - protocol of a randomized controlled trial." Trials 24(1): 376.
	Background: Obesity represents a growing threat to health with multiple negative impacts including urinary incontinence. Pelvic floor muscle training (PFMT) is the first line of treatment for urinary incontinence. Both surgical and conservative weight loss results in improvement of urinary incontinence reports in obese women and we hypothesize that a low-calorie diet in combination with PFMT would result in additional beneficial effects to urinary symptoms in women with UI compared would with weight loss alone. Objective(s): To assess the effect of a low-calorie diet plus PFMT protocol in obese women's urinary incontinence reports. Method(s): This is a protocol for a randomized controlled trial that will include obese women reporting UI and being able to contract their pelvic floor muscles. The participants will be randomly allocated in two groups: group 1 will participate in a 12-week protocol of low-calorie diet delivered by a multi-professional team at a tertiary hospital; group II will receive the same low-calorie diet protocol during 12 weeks and will additionally participate in 6 group sessions of supervised PFMT delivered by a physiotherapist. The primary outcome of the study is self-reported UI, and severity and impact of UI on women's quality of life will be assessed by the ICIQ-SF score. The secondary outcomes will be adherence to the protocols assessed using a home diary, pelvic floor muscle function assessed by bidigital vaginal palpation and the modified Oxford grading scale, and women's self-perception of their PFM contraction using a questionnaire. Satisfaction with treatments will be assessed using a visual analog scale. The statistical analysis will be performed by intention to treat and multivariate analysis of mixed effects will be used to compare outcomes. The complier average causal effects (CACE) method will be used to assess adherence. There is an urgent need for a high-quality RCT to investigate if the association of a low-calorie diet and PFMT can provide a larger effect in the improvement of urinary incontinence reports in women with obesity. Trial registration: Clinical Trials NCT04159467. Registered on 08/28/2021.Copyright © 2023, The Author(s).

Méndez-Sánchez, L., et al. (2023). "Calcium and vitamin D for increasing bone mineral density in premenopausal women." Cochrane Database of Systematic Reviews(1).
	- Background Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life. Objectives To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo. Search methods We used standard, extensive Cochrane search methods. The latest search was 12 April 2022. Selection criteria We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D 3 ) or ergocalciferol (vitamin D 2 ). Data collection and analysis We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non‐vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason. Main results We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) −0.04 g/cm 2 , 95% confidence interval (CI) −0.11 to 0.03; I 2 = 71%; 3 studies, 174 participants; low‐certainty evidence; lumbar spine BMD: MD 0 g/cm 2 , 95% CI −0.06 to 0.06; I 2 = 71%; 4 studies, 202 participants; low‐certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I 2 = 0%; 4 studies, 261 participants: moderate‐certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (R 0.74, 95% CI 0.46 to 1.19; moderate‐certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (−0.03, 95% CI −0.06 to 0; moderate‐certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI −0.01 to 0.03; moderate‐certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I 2 = 72%; 2 studies, 541 participants; low‐certainty evidence). Authors' conclusions Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non‐vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful. Plain language summary Calcium and vitamin D for improving bone health in healthy premenopausal women Key messages The evidence suggests that calcium, vitamin D, or calcium plus vitamin D supplementation has no effect on bone mineral density at any site (hip or spine) in healthy premenopausal women. What is osteoporosis? Osteoporosis is characterised by low levels of calcium and other types of minerals in the bones (called bone mineral density). This causes holes to form inside the bones and the outer walls of the bone to become thin making the bones more fragile, which may lead to increased fractures and breaks. Osteoporosis constitutes a major public health problem and contributes to more than 8.9 million broken bones annually, which means that on average, an osteoporotic fracture occurs every three seconds. Supplements of calcium and vitamin D are often recommended for women after menopause (although not everyone agrees), but adequate supplementation of calcium and vitamin D is always recommended in institutionalised people (e.g. people living in care homes) and people taking osteoporosis treatment. Little is known about the effect of calcium and vitamin D on the bone density of women who have not yet started menopause. There are few studies in this age group and the results are inconclusive. In this age group, increasing bone strength and health is considered the goal of supplementation, so BMD is relevant. What did we want to find out? We wanted to determine if calcium and vitamin D were able to increase the mineral content of bones and reduce the risk of fractures, and to report potential side effects of supplementation. What did we do? We searched medical databases for well‐designed clinical studies of calcium and vitamin D supplementation alone or in combination compared with placebo (dummy treatment) in healthy women aged 18 to 45 years (premenopausal). We analysed three combinations: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo, administered for at least three months. We looked at their effects on increasing minerals in the bones of the hip and spine, if the women had vertebral (backbone) or any other fractures during the study, effects on quality of life, and if these women had to stop the supplementation because of side effects. What did we find? We included seven studies with 941 healthy premenopausal women with an average age per study of 18 to 42.1 years. The women were randomly assigned t receive supple entation of calcium, vitamin D, or vitamin D plus calcium, or placebo. Main results There was no difference in bone mineral density in any of the groups being supplemented with calcium, vitamin D, or calcium plus vitamin D compared with placebo. The studies did not report fractures (from any anatomical site), quality of life, or stopping the supplementation for side effects. What are the limitations of the evidence? The common limitations in the methods of the studies included small numbers of participants, studies, and data; problems in adherence to treatment, participants may have known which treatment they received; and lack of information for withdrawals from treatment. The funding for the studies was provided by institutional, academic, government, and pharmaceutical industries. How up to date is this evidence? The evidence is up to date to April 2022.

Mendling, W., et al. (2020). "Clotrimazole for Vulvovaginal Candidosis: More Than 45 Years of Clinical Experience." Pharmaceuticals (Basel, Switzerland) 13(10).
	Vulvovaginal candidosis is a common disease, and various treatment strategies have emerged over the last few decades. Clotrimazole belongs to the drugs of choice for the treatment of vulvovaginal candidosis. Although available for almost 50 years, systematic reviews on the usefulness of topical clotrimazole across disease severity and populations affected are scarce. Thus, we conducted a systematic literature search in the PubMed and Embase databases to summarize the effectiveness and safety of topical clotrimazole in the treatment of uncomplicated (acute) and complicated vulvovaginal candidosis. In total, 37 randomized controlled studies in women suffering from vaginal yeast infections qualified for inclusion in our review. In women with uncomplicated vulvovaginal candidosis, single intravaginal doses of clotrimazole 500 mg vaginal tablets provided high cure rates and were as effective as oral azoles. A single dose of clotrimazole 500 mg was equipotent to multiple doses of lower dose strengths. Prolonged treatment regimens proved to be effective in severe and recurrent cases as well as in symptomatic pregnant women. It is therefore expected that in the general population, clotrimazole will continue to be widely used in the field of vaginal health in the upcoming years; more so as clotrimazole resistance in vaginal candidosis is rare.

Menefee, S., et al. (2023). "A randomized trial of sacral colpopexy, transvaginal mesh, and native tissue apical repair for post-hysterectomy vault prolapse." American Journal of Obstetrics and Gynecology 228(3 Supplement): S797.
	Objectives: To compare the efficacy and safety of three post-hysterectomy apical repairs Material(s) and Method(s): This randomized trial compared postoperative outcomes in women randomized to sacral colpopexy, transvaginal mesh, or native tissue followed for 36 to 60 months at 9 clinical sites. Anatomic evaluators remained masked to treatment assignment. Time to composite treatment failure (prolapse re-treatment, prolapse beyond the hymen, or prolapse symptoms) up to 60 months was evaluated with piecewise exponential survival models with alpha adjustment for 3 comparisons. Secondary outcomes measured every 6 months included patient-reported symptom-specific outcomes, functional efficacy and adverse events. Results from 36 months are reported since all participants completed this assessment. Result(s): 376 participants were randomized, 360 were treated (mean age, 66 years), and 296 (82%) completed planned study follow-up. Time to treatment failure (Figure 1) for transvaginal mesh was non-inferior to sacral colpopexy at the pre-determined hazard ratio margin of 1.93 (adjusted hazard ratio [HR], 1.05 [upper 1-sided 97% CL, 1.65, p=0.01). Statistical superiority over native tissue repair was seen with sacral colpopexy (adjusted HR, 0.57 [2-sided 99% CI, 0.33, 0.98], p=0.01) but not with transvaginal mesh (adjusted HR, 0.60 [2-sided 99% CI, 0.34, 1.03] p=0.02). Maximum postoperative leading edge including POP-Q points Ba, Bp, and C at 36 months (mean, [95%CL]) was better in the sacral colpopexy (-1.4, [-1.6 to -1.1]) group compared to both the transvaginal mesh (-0.9, [-1.2 to -0.7], p=0.03) and native tissue groups (-0.6, [-0.9 to -0.4], p<0.001). Perioperative outcomes and adverse events for sacral colpopexy, transvaginal mesh, and native tissue, respectively, included operative time in minutes (218, 128, 123), estimated blood loss in mL (104, 111, 96), mesh exposure (3%, 5%, N/A), urinary tract infections (31%, 53%, 49%), granulation tissue (4%, 7%, 15%), and suture exposure (5%, 3%, 14%). At 36 months, all treatment arms showed sustained improvement over baseline in patient-reported outcomes (Figure 2) including pelvic floor and prolapse symptoms, urinary function, bowel function, sexual function, and quality of life, with notable differences between groups in the Pelvic Floor Distress Inventory (PFDI) subscales, Colorectal Anal Impact Questionnaire (CRAIQ), and Short Form Health Survey mental component. Notably, there were no differences in decision regret/satisfaction scale scores across treatment arms. Conclusion(s): Among women seeking apical repair for post-hysterectomy vault prolapse, both sacral colpopexy and transvaginal mesh resulted in a lower composite failure rate compared to native tissue after a minimum of 36 months; however, only sacral colpopexy reached statistical significance. Results of safety and secondary efficacy outcomes varied. All three treatments resulted in sustained benefits for the majority of subjective outcomes. [Formula presented] [Formula presented]Copyright © 2022

Meneses-Echavez, J. F., et al. (2023). "Prehabilitation programs for individuals with cancer: a systematic review of randomized-controlled trials." Systematic Reviews 12(1): 219.
	BACKGROUND: Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients' outcomes before cancer surgery. This systematic review determined the benefits and harms of prehabilitation programs compared with usual care for individuals with cancer. METHODS: We searched CENTRAL, MEDLINE, and EMBASE from inception to June 2022, and hand searched clinical trial registries. We included randomized-controlled trials (RCTs) in adults, survivors of any type of cancer, that compared prehabilitation programs that had exercise training as the major component with usual care or other active interventions. Outcome measures were health-related quality of life (HRQL), muscular strength, postoperative complications, average length of stay (ALOS), handgrip strength, and physical activity levels. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias and the certainty of the evidence. RESULTS: Twenty-five RCTs (2682 participants) published between 2010 and 2022 met our inclusion criteria. Colorectal and lung cancers were the most common diagnoses. The studies had methodological concerns regarding outcome measurement, selective reporting, and attrition. Five prehabilitation programs were compared to usual care (rehabilitation): combined training, aerobic training, respiratory muscle training plus aerobic training, respiratory muscle training plus resistance training, and pelvic floor training. The studies provided no clear evidence of an effect between groups. We assessed the overall certainty of the evidence as very low, downgraded due to serious study limitations and imprecision. CONCLUSION: Prehabilitation programs focusing on exercise training may have an effect on adults with cancer, but the evidence is very uncertain. We have very little confidence in the results and the true effect is likely to be substantially different from these. Further research is needed before we can draw a more certain conclusion. SYSTEMATIC REVIEW REGISTRATION: CRD42019125658.

Menezes, E. C., et al. (2022). "Effect of exercise on female pelvic floor morphology and muscle function: a systematic review." International Urogynecology Journal.
	INTRODUCTION AND HYPOTHESIS: The objective was to synthesize the scientific evidence on the relationship of exercise with morphology and muscle function parameters of the female pelvic floor. The design was a systematic review with meta-analysis. METHODS: Searches were performed in MEDLINE, PubMed, CINAHL, Web of Science, SCOPUS, SportDiscuss, and Google Scholar up to April 2021. Observational and experimental studies evaluating the morphology and/or function of the pelvic floor muscles (PFMs) in women were eligible. Studies reporting exercise or sports disciplines as exposure/intervention were included. RESULTS: Twenty-five studies were included. Compared with the control group, women performing vigorous and high-impact exercises exhibited lower maximum voluntary contraction of the PFM and those performing moderate exercise had better maximum voluntary contraction. Exercise practitioners had a larger hiatal area at rest, during contraction, and during Valsalva, and greater bladder neck descent than the control group. CONCLUSIONS: The results of this review demonstrate an inverse relationship of PFM maximum voluntary contraction with exercise intensity. Qualitative synthesis showed that the studies found favorable outcomes for the control group in terms of hiatal area during contraction and Valsalva and bladder neck displacement.

Meng, B., et al. (2023). "Current status and outlook of minimally invasive treatment for leiomyomas." Ginekologia polska.
	OBJECTIVES: Leiomyomas are benign, highly prevalent gynecologic conditions that can cause abnormal uterine bleeding, pelvic pain, urinary difficulties, and/or bladder or rectal obstruction. With advances in medical technology, women are increasingly interested in treatments that avoid surgery and/or preserve the uterus, which has undoubtedly contributed to the development of minimally invasive approaches. This article reviews the literature and evaluates the effectiveness and safety of minimally invasive approaches for the treatment of leiomyomas and describes the current state of development of minimally invasive treatment modalities for leiomyomas. MATERIAL AND METHODS: Web of Science and PubMed were systematically evaluated using the following keywords: uterine artery embolization, high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, myomectomy, hysterectomy, leiomyomas, fertility. English abstracts relevant to the topic were selected and full-text articles were carefully analyzed. RESULT(S): Uterine artery embolization is an effective treatment modality that has been widely validated, and the remaining means each have their distinct advantages in clinical practice, but more practical and comparative studies are needed. Minimally invasive myomectomy and minimally invasive hysterectomy are technically advanced compared to classical open surgery and are widely used due to the completion of practical experience, but a continuous interest in non-invasive minimally invasive treatment modalities is retained. CONCLUSION(S): Minimally invasive treatment modalities for leiomyomas have emerged as an important treatment option when considering patient requirements, and further research and practice are needed to support their development into a mainstream modality for the treatment of leiomyomas.

Meng, d., et al. (2023). "Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery."
	Review question [1 change] Evaluate the results related to chronic postoperative pain caused by adhesive surgery treatment. Searches [2 changes] We will use the Boolean operator AND/OR to retrieve chronic pain, abdominal pain, pelvic pain, tissue adhesions, laparoscopic surgery, and laparotomy (all fields, MeSH term) in PubMed, EMBASE, and Web of Science databases. There are no language and date restrictions. Search in November 2023. Types of study to be included All prospective and retrospective cohort studies that meet inclusion criteria. Condition or domain being studied [1 change] Chronic pain is a common postoperative complication that affects approximately 20-40% of female patients undergoing genital or gastrointestinal surgery. Chronic pain is an important risk factor for postoperative decline in quality of life. Adhesion is usually associated with postoperative chronic pain; However, the surgical treatment of adhesion-related pain is still controversial, and research on the efficacy and harm of surgical intervention on chronic postoperative pain caused by adhesions has only been reported in 2017. In addition, this study included only 13 studies and only two randomized trials. The current evidence quality is low, with many biases and heterogeneity. More high-quality randomized trials are needed to validate the effectiveness and safety of surgical interventions. Participants/population [2 changes] The inclusion criteria include pain and adhesions caused by previous surgeries, chronic pain lasting at least 3 months, and a minimum follow-up interval of 3 months. The exclusion criteria are patients with accompanying diagnosis and those who have not provided raw data in the study. The study of adhesion patients with different etiologies, such as endometriosis and inflammatory diseases, is only considered qualified if data from a subgroup of postoperative adhesion patients can be extracted separately. Intervention(s), exposure(s) Laparoscopic adhesiolysis with adhesive barrier. Comparator(s)/control Laparoscopic adhesiolysis without adhesive barrier. Main outcome(s) [1 change] Pain score (VAS or NRS), pain improvement Measures of effect Due to the risk of recurrence, the results will be compared at different time scales. Mid term: 3 to 12 months; Long term 1:>12 months; Long term 2:>24 months. Additional outcome(s) [1 change] Pain worsening, resumption of daily activities, negative laparoscopy/exploratory laparotomy, adverse events. Measures of effect Laparoscopic examination/exploratory laparotomy negative, adverse events: perioperative and short-term (30 days) postoperative or intervention outcomes. Data extraction (selection and coding) Data extraction: Data extraction will be conducted independently by two reviewers. Data extraction will include: Number of patients, diagnostic method for adhesions, type of intervention, number of patients with pain relief, pain improvement, pain worsening, pain score, use of painkillers, hospital visits, general practitioner visits, adverse events, number of adhesion-negative surgeries. Risk of bias (quality) assessment Two evaluators will independently evaluate the quality of methodology. The methodological quality included in the study will be rated based on the revised version of the Newcastle Ottawa scale: Queue selection: Two evaluators will independently evaluate the quality of methodology. The methodological quality included in the study will be scored based on the Cochrane bias risk tool. The publication bias of the included study will be evaluated through a funnel plot. We will also search the trial registry (international clinical trial registration platform and UK clinical trial portal) to find relevant records of completed unpublished studies. Data related to experimental sponsorship will be recorded and reported. Strategy for data synthesis The Mantel Haenszel method will be used for merging binary data, and the results will be represented by relative risk (RR) and its 95% confidence interval (CI). A p-value of<0.05 will be considered significant. The inverse variance method will be used for the consolidation of continuous data, and the results will be represented by the standardized mean difference (SMD) and its 95% CI. Heterogeneity will be explored through the Cochran test. The significance is set to a p-value of 0.10, and the quantity of heterogeneity is measured by I². A fixed effects model will be used for meta-analysis. In the presence of significant statistical heterogeneity, a random effects model will be used. The data will be analyzed using Review Manager 5.0. Analysis of subgroups or subsets We will group according to the type of intervention. Contact details for further information Meng die Wang 2328177142@qq.com Organisational affiliation of the review Kunming University of Science and Technology Review team members and their organisational affiliations [1 change] Miss Meng die WANG. kunming university of science and technology Miss Ying hui YU. Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 01 December 2023 Anticipated completion date 31 December 2026 Funding sources/sponsors [1 change] No funds available. Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms MeSH headings have not been applied to this record Date of registration in PROSPERO 27 November 2023 Date of first submission 16 November 2023

Meng, J., et al. (2022). "Effects of an evidence-based nursing intervention on prevention of anxiety and depression in the postpartum period." Stress and health : journal of the International Society for the Investigation of Stress 38(3): 435-442.
	Postpartum depression has been one of the most common psychological disorders in patients during postpartum period. The constant anxiety and depression during this period seriously affect the physiological and psychological health of both the mother and infant. Evidence-based nursing has been widely applied in clinical practice and has achieved remarkable results. However, the effect of evidence-based nursing on postpartum depression remains unclear. Pregnant women who were not diagnosed with postpartum depression during hospitalisation (Edinburgh Postpartum Depression Scale [EPDS] ≤ 13 points) but prone to postpartum depression (EPDS scores of 9-13) were recruited into the study. They were randomly divided into the Intervention group (N = 60) and Control group (N = 60). Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), EPDS and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the psychological outcomes of puerperae during and after the 6-week intervention. Both the intention-to-treat and per-protocol analyses showed that 6 weeks of evidence-based nursing intervention significantly reduced the incidence of postpartum depression. The application of the evidence-based nursing also improved the patients' satisfaction degree and effectively alleviated their anxiety according to both the intention-to-treat and per-protocol analyses. Evidence-based nursing intervention had positive effects against anxiety and depression in the postpartum period. (© 2021 John Wiley & Sons, Ltd.)

Meng, Q. (2021). "Therapeutic effect of mifepristone combined with sublingual misoprostol on missed abortion." 河南医学研究 30(5): 916‐918.
	Objective: To investigate the therapeutic effect of mifepristone combined with sublingual misoprostol on missed abortion. Methods: A total of 84 missed abortion patients admitted to Qixian People's Hospital from February 2019 to February 2020 were selected as the research objects, and divided into an observation group and a control group according to the random number table method, with 42 cases in each. The control group was given mifepristone for treatment, and the observation group was given sublingual misoprostol on the basis of the control group. The complete abortion rate on the 4th day after treatment, the levels of vascular endothelial growth factor (VEGF) before treatment and on the 4th day after treatment were compared between the two groups, and the occurrence of adverse reactions (lower abdominal pain, vomiting, dizziness) during the treatment was compared between the two groups. Results: The complete abortion rate in the observation group was 88.10%, which was higher than 33.33% in the control group, and the difference was statistically significant (P<0.05). , the difference was statistically significant (P<0.05). Conclusion: For patients with missed abortion, combined with sublingual misoprostol on the basis of mifepristone, the complete abortion rate can be further improved and the serum VEGF level can be reduced without increasing adverse reactions.

Meng, Q., et al. (2022). "Noninvasive embryo evaluation and selection by time-lapse monitoring vs. conventional morphologic assessment in women undergoing in vitro fertilization/intracytoplasmic sperm injection: a single-center randomized controlled study." Fertility and Sterility 117(6): 1203-1212.
	Objective: To determine whether time-lapse monitoring (TLM) for cleavage-stage embryo selection improves reproductive outcomes in comparison with conventional morphological assessment (CMA) selection.; Design: Prospective randomized controlled trial.; Setting: Single academic center.; Patients: We randomly assigned 139 women who were undergoing their first in vitro fertilization or intracytoplasmic sperm injection cycle to undergo either fresh embryo transfer or first frozen embryo transfer (FET). Only 1 cleavage-stage embryo was transferred to each participant.; Interventions: The patients were randomly assigned to either the CMA or the TLM group. In the CMA group, day 2 and day 3 embryos were observed. A good-quality cleavage-stage embryo was selected for transfer or freezing in both groups.; Main Outcome Measures: The primary and secondary outcomes were the clinical pregnancy rate (CPR) and the live birth rate (LBR), respectively, after the first embryo transfer (fresh embryo transfer or FET).; Results: The CPR and LBR were significantly lower in the TLM group than in the CMA group (CPR: 49.18% vs. 70.42%; relative risk, 0.70; 95% confidence interval [CI], 0.52-0.94; LBR: 45.90% vs. 64.79%; relative risk, 0.71; 95% CI, 0.51-0.98). The CPR with fresh embryo transfer or FET did not significantly differ between the TLM and the CMA groups (fresh embryo transfer: 44.44% vs. 70.0%, relative risk, 0.63, 95% CI, 0.39-1.03; FET: 52.94% vs. 70.73%, relative risk, 0.75, 95% CI, 0.52-1.09). There was a significant difference in the LBR with fresh embryo transfer between the TLM and the CMA groups (40.74% vs. 66.67%; relative risk, 0.61; 95% CI, 0.36-1.03). The LBRs with FET were similar in the TLM and the CMA groups (50.0% vs. 63.41%; relative risk, 0.79; 95% CI, 0.52-1.19). The rates of early spontaneous abortion and ectopic pregnancy did not differ between the TLM and the CMA groups.; Conclusions: Elective single cleavage-stage embryo transfer with TLM-based selection did not have any advantages over CMA when day 2 and day 3 embryo morphology was combined in young women with a good ovarian reserve. Because of these results, we conclude that TLM remains an investigational procedure for in vitro fertilization practice.; Clinical Trial Registration Number: ChiCTR1900021981. (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Meng, W., et al. (2021). "Tumour-shrinking decoction for symptomatic uterine fibroids: a double-blind, randomised, two-dose trial (abridged secondary publication)." Hong kong medical journal 27 Suppl 2(3): 8‐10.
	
Meng, W., et al. (2019). "Add-on effect of Guizhi Fuling formula to mifepristone for endometriosis: A meta-analysis of randomized controlled trials." Medicine 98(33): e16878.
	Background: Guizhi Fuling pill, a famous traditional Chinese herbal formula, has been widely used for treatment of gynecological diseases. This meta-analysis sought to evaluate the add-on effect of Guizhi Fuling capsule (GZFL) to mifepristone in women with endometriosis.; Methods: A comprehensively literature search was conducted using Pubed, Embase, Cochrane Library, Wanfang, CNKI, VIP databases from their inceptions to January 25, 2019. Randomized controlled trials that compared GZFL plus mifepristone to mifepristone alone for treatment of endometriosis were eligible. Main outcomes were pregnancy, reduction of the recurrence, and serum level of follicle-stimulating hormone, luteinizing hormone, estradiol or progesterone.; Results: A total of 1052 women with endometriosis from 10 trials were identified and analyzed. Meta-analyses showed that GZFL plus mifepristone was superior to mifepristone in reducing the recurrence of endometriosis (RR 0.40; 95% CI 0.27-0.59) and improving the pregnancy (risk ratio [RR] 1.74; 95% confidence intervals [CI] 1.40-2.17). Moreover, adjuvant treatment with GZFL also significantly reduced serum level of estradiol (mean difference [MD] -20.83 pmol/L; 95% CI -34.01 to -7.65) and progesterone (MD -0.18 mmol/L; 95% CI -0.23 to -0.12). However, there were no significant differences in serum level of follicle-stimulating hormone (MD -0.42 U/L; 95% CI -1.16 to 0.31) and luteinizing hormone (MD -0.04 U/L; 95% CI -0.43 to 0.34).; Conclusion: GZFL as adjuvant therapy to mifepristone appears to have additional benefits in preventing recurrence of endometriosis and improving pregnancy among women with endometriosis. However, these conclusions should be interpreted with caution due to the methodological flaws of the included trials.

Mengato, D., et al. (2022). "Indirect comparison of three PARP inhibitors (olaparib, niraparib, and rucaparib) as maintenance treatment in ovarian carcinoma patients responding to platinum therapy." International journal of clinical pharmacology and therapeutics 60(8): 370-372.
	
Mengdie, Y. and S. Wei (2021). "Clinical efficacy of Integrative Chinese-Western Medicine intreatment of adenomyosis: a systematic review and meta-analysis."
	Review question The aim of this meta-analysis of randomized controlled trials is to evaluate the efficacy of Integrative Chinese-Western Medicine for adenomyosis Searches We will search, with no time restriction, the folloeing databases for relevant English language literature: PubMed (MEDLINE), Web of Science and Green Medical; for relevant Chinese language literature: CNKI, Wanfang, COVIP. The search string will be built as follows: (adenomyosis) and (combine) and (decoction) and (pill) Types of study to be included Randomized controlled trials (RCTs) will be included Condition or domain being studied

Mengfei, Y. and L. Zheng (2021). "The Efficacy of Cognitive Behavior Therapy for Women with Menopausal Symptoms: A Meta-analysis of Randomized Controlled Trials." PROSPERO International prospective register of systematic reviews.
	Review question The primary objective of the current study was to conduct estimate of the efficacy of cognitive behavior therapy for alleviating menopausal symptoms at post-intervention and follow-up. We hypothesized that cognitive behavior therapy are efficacious in reducing menopausal symptoms. A secondary aim was to explore the difference between during the menopausal transition and following other treatment. The third intention was to explore the possible influence of between-study differences in participants, intervening duration, forms of intervention, delivery methods, and control groups. Searches [1 change] We conducted keyword-based searches in Cochrane Library, EMBASE, PsycINFO, PubMed and Web of Science databases. The keywords related to menopausal symptoms (e.g, Perimenopausal or Postmenopausal or Climacteric) were combined with keywords related to CBT. Literature search dates encompassed January 1, 1966, to May 1, 2021. English language articles published in peer-reviewed sources were included. Types of study to be included Included studies are randomized controlled trials (RCTs) Condition or domain being studied Menopausal symptoms Participants/population Women with menopausal symptoms, which during menopausal transition, following breast cancer treatment, or following other treatment. Intervention(s), exposure(s) Cognitive behavior therapy is defined as a therapy in which cognitive restructuring was one of the core components. Cognitive restructuring was aimed at evaluating, challenging, and modifying participants’ dysfunctional beliefs. Comparator(s)/control Eligible studies are required to use a control group. For example, wait list, treatment as usual, or attention/active control (e.g, menopause education). Main outcome(s) Pre- and post-intervention data, or pre-post change score data on quantitative menopausal symptoms relevant construct. Measures of effect Effect sizes were determined by subtracting the average score of the control group from the average score of cognitive behavior therapy group, and dividing the result by the pooled standard deviation. Additional outcome(s) None Data extraction (selection and coding) Two authors remove duplicates and screening the records, ensuring that all records are independently evaluated by two authors. Full texts of the remaining articles are evaluated and registered reasons of excluded articles. And disagreements are discussed with a third author until a consistent conclusion is reached. Data of included studies are extracted by one author and checked by another author. ESs are calculated using means and standard deviations for pre-intervention, post-intervention, or change scores. Risk of bias (quality) assessment The Cochrane Collaboration tool is adapted to evaluate the risk of bias within the context of CBT intervention studies. Strategy for data synthesis Effect sizes (ESs) are calculated using means and standard deviations for pre-intervention, post-intervention, or change scores. Random-effects model is chosen for all analyses, with positive values of ESs indicating higher scores after treatment. To calculate pooled mean effect sizes, we use Stata (version 15.1). Analysis of subgroups or subsets Analysis of subgroups include participants, intervening duration, forms of intervention, delivery methods, and control groups. Contact details for further information Mengfei Ye mengfeiye1107@163.com Organisational affiliation of the review Department of Psychiatry, Shaoxing Seventh People's Hospital Review team members and their organisational affiliations Dr Mengfei Ye. Department of Psychiatry, Shaoxing Seventh People's Hospital Dr Zheng Liu. Department of Clinical Medicine, Medical College of Shaoxing University, Shaoxing, Zhejiang, China Type and method of review Intervention, Meta-analysis, Systematic review Anticipated or actual start date 06 May 2021 Anticipated completion date 15 June 2021 Funding sources/sponsors Zhejiang Medical Health Science and Technology Project Grant number(s) State the funder, grant or award number and the date of award Zhejiang Medical Health Science and Technology Project (No. 2020KY332) Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Cognitive Behavioral Therapy; Female; Hot Flashes; Humans; Menopause; Randomized Controlled Trials as Topic Date of registration in PROSPERO 01 June 2021 Date of first submission 29 April 2021 Stage of review at time of this submission The review has not started

Mengke, Y., et al. (2023). "Acupuncture for the treatment of tubal infertility: a protocol of A systematic review and meta-analysis."
	Review question [1 change] If acupuncture improve the pregnancy rate in women with tubal infertility? Searches PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Cumulative Index for Nursing and Allied Health Literature (CINAHL), and the Excerpta Medica Database (EMBASE) from inception to 2023.2 Types of study to be included [1 change] RCTs Condition or domain being studied Abundant clinical research reported the effect of acupuncture on pregnancy rate in women with tubal infertility, but the systematic review and meta-analysis is absent. This review will evaluate the clinical efficacy and safety of acupuncture on the women of tubal infertility. Participants/population [1 change] Women of childbearing age (20–40 years) failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, and were identified tubal obstructed by Hysterosalpingography (HSG) or Hysterosalpingocontrast sonography (HyCoSy) or Laparoscopy with chromopertubation. We will exclude women who was identified with other infertile factors (anovulation, endometriosis, genital tract congenital malformation), and whose male partner has history of abnormal semen analysis results, vasectomy reversal, or male factor infertility. Intervention(s), exposure(s) [1 change] Acupuncture Comparator(s)/control [1 change] sham acupuncture/non-treatment/usual care/health guidance/any other active therapies cupuncture combined with other interventions will also be considered, provided both interventions were given to both comparis Main outcome(s) [1 change] Pregnancy confirmed with a pregnancy test or ultrasound Additional outcome(s) [1 change] tubal recanalization, abdominal pain, anxiety and depression, adverse events Data extraction (selection and coding) [1 change] Endnotes 9 software will be used to manage retrieved literatures. Two authors (MKY and FQS) will independently screen titles and abstracts for potential inclusion and then review full-text articles, including reference lists, to determine their eligibility. The eligible articles will be subjected to extract the following data: 1. trial characteristics (author, publication date, study design); 2. participant characteristics (age, duration of disease, sample size); 3. treatment regime; 4. control intervention; 5. outcomes. Any disagreement about the included literature or data extraction will be resolved after discussion with a third researcher (BWH). Risk of bias (quality) assessment [1 change] We will evaluate the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Strategy for data synthesis [1 change] The meta-analysis will be performed using Stata Version 17 software (Stata Corp, College Station, TX, USA). Continuous data will be described by mean difference (MD) with 95% credible interval. Relative risk (RR) and 95% CI will be calculated for dichotomous data. Statistical heterogeneity will be assessed using I² statistic and Cochranes Q test. If p ≥ 0.05 and I² ≤ 50%, a fixed effects model will be used to confirm collective effectiveness, if p < 0.05 or I² > 50%, random effects models will be used. Funnel plot analyses will be used to assess publication bias. Analysis of subgroups or subsets [1 change] If there is enough evidence, we will perform subgroup analysis according to types of acupuncture and control interventions. Contact details for further information Mengke Yuan 18845058507@163.com Organisational affiliation of the review Heilongjiang University of Chinese Medicine Review team members and their organisational affiliations Dr Mengke Yuan. Heilongjiang University of Chinese Medicine Dr Fanqi Shen. Heilongjiang University of Chinese Medicine Professor Li Liu. The First Affiliated Hospital of Heilongjiang University of Chinese Medicine Professor Yiming Sun. Heilongjiang Academy of Chinese Medicine Science Dr Buwei Han. Heilongjiang University of Chinese Medicine Yukun Fan. Heilongjiang University of Chinese Medicine Dr Xianling Cao. Shandong University of Chinese Medicine Type and method of review Meta-analysis, Systematic review Anticipated or actual start date [1 change] 15 April 2023 Anticipated completion date 31 July 2023 Funding sources/sponsors This study is supported by the central support fund for the reform and development of local universities [2021ZYGLG001] Conflicts of interest Language (there is not an English language summary) Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Acupuncture Therapy; Female; Humans; Infertility; Meta-Analysis as Topic; Pregnancy; Pregnancy Rate; Systematic Reviews as Topic Date of registration in PROSPERO 23 February 2023 Date of first submission 13 February 2023 Stage of review at time of this submission

Mengyao, C., et al. (2022). "Effectiveness of auricular acupoint therapy on menstrual pain for primary dysmenorrhea: A systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	Review question Is auricular acupoint therapy effective in reducing menstrual pain and the accompanying symptoms among females with PD? 2) Is auricular acupoints therapy more effective than NSAIDs in relieving menstrual pain in PD? Searches Database that will be searched include PubMed, EMBASE, AMED, CINAHL Plus, Cochrane Library, and Web of Science, China National Knowledge Infrastructure and Wanfang Data. The language of publication will be limited to English and Chinese. No filters will be used during the search. Types of study to be included RCTs published in English or Chinese with the randomization method reported. Condition or domain being studied primary dysmenorrhea Participants/population Females with primary dysmenorrhea Intervention(s), exposure(s) The intervention is auricular acupoint therapy. Auricular acupoint therapy is a conventional Traditional Chinese Medicine treatment using acupoint stimulation on the ear(s) to treat diseases. All types of auricular acupoint therapy that are not combined with other therapies will be included. Comparator(s)/control Controls include all forms of placebo auricular acupoint therapies and NSAIDs. Context No restrictions on the setting. Main outcome(s) Menstrual pain as a continuous variable measured by validated instruments Measures of effect Mean difference Additional outcome(s) Menstrual symptoms Adverse effects Measures of effect Mean difference or narrative synthesis Data extraction (selection and coding) Data related to the investigated outcome will be extracted by two reviewers, including study identity, study design, sample size, characteristics of participants and interventions, attrition, adverse reactions, outcome measure, and outcome statistics. Risk of bias (quality) assessment Risk of bias of the included studies will be assessed using Rob 2.0. Evidence certainty will be judged according to GRADE criteria. Strategy for data synthesis Data will be transferred into Covidence(2022) and STATA(16.0) softwares accordingly for analysis and synthesis. The effect sizes will be presented as Mean Difference (MD) or Standard Mean Difference with 95% confidence interval (CI), imputing based on the post-intervention data. P <0.05 will be considered statistically significant, with high heterogeneity indicated by p<0.1 in Cochran's Q test and and I squared index larger than 50%, in which contidition a random-effects model will be adopted for pooling instead of fix-effect model. Analysis of subgroups or subsets Subgroups analysis will be performed by characteristics of intervention, such as type, duration, acupint selection, providers. Contact details for further information Mengyao Cao u3590805@connect.hku.hk Organisational affiliation of the review The University of Hong Kong Review team members and their organisational affiliations Miss Mengyao Cao. The University of Hong Kong Mrs Fen Ye. The University of Hong Kong Dr Jung Jae Lee. The University of Hong Kong Miss Wenxuan Xie. The University of Hong Kong Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 09 August 2022 Anticipated completion date 08 October 2022 Funding sources/sponsors None Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Acupressure; Acupuncture Points; Dysmenorrhea; Female; Humans; Pain Measurement Date of registration in PROSPERO 26 August 2022 Date of first submission

Menichini, D. and F. Facchinetti (2020). "Effects of vitamin D supplementation in women with polycystic ovary syndrome: a review." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 36(1): 1-5.
	Increasing evidence supports the contribution of vitamin D deficiency (VDD) in metabolic disturbances among women with polycystic ovary syndrome (PCOS). This review aims to assess the associations between vitamin D levels and metabolic/endocrine dysregulations and to determine the effects of vitamin D supplementation on glucose metabolism, insulin sensitivity, lipid profile, and hormones functionality in PCOS patients. We searched in PubMed human randomized controlled trials (RCTs) published in English between 2016 and 2019 on the effects of vitamin D supplementation on PCOS. Nine studies were included and analyzed. Vitamin D supplementation restored physiological serum 25(OH)D levels in PCOS women in all the studies included. In six studies, it significantly decreased fasting plasma glucose and brought to improvements in insulin resistance (IR) and serum fasting insulin. In addition, four studies reported decreases of serum triglycerides, while discordant data are reported as far as LDL, HDL, and total cholesterol levels. High-doses of vitamin D (4000 IU), compared with low-dose (1000 IU), and placebo, showed beneficial effects on total testosterone, sex hormone-binding globulin (SHBG) and free androgen index (FAI). Vitamin D supplementation at high doses for a period of at least 12 weeks, may lead to improvement in terms of glucose level, insulin sensitivity, hyperlipidemia, and hormonal functionality in PCOS women.

Menichini, D., et al. (2022). "Nutraceuticals and polycystic ovary syndrome: a systematic review of the literature." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(8): 623-631.
	Background This study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS).The aim is to provide a classification of the most widely used nutraceutical supplements identifying the most effective nutraceuticals on glucose and insulin metabolism, the androgenic hormone profile, fertility, ovulatory capacity, inflammation, and oxidative stress. Material and Methods We included randomized controlled trials on PCOS patients undergoing administration of nutraceuticals, in particular vitamin D, vitamin E, probiotics, and inositols. These administrations are variable in terms of dosage, single supplementation, or combined with other compounds, dosage, and duration of the intervention. Results The supplementation of inositols, at the physiologic ratio of 40: 1 of myo- and D-chiro-inositols, resulted to be the most effective in improving the glucose homeostasis and fertility, with a restoration of ovulatory capacity and menstrual regularity. Other nutraceuticals are particularly effective in reducing hyperandrogenism, with promising results demonstrated by the combinations of vitamin D and probiotics, vitamin E and coenzyme Q10, and the enrichment of inositol therapy with group B vitamins. An improvement in the inflammatory status and antioxidant capacity is obtained with the co-supplementation of probiotics and selenium or with vitamin E combined with omega 3. Conclusions Inositol supplementation is effective in the treatment of insulin resistance and fertility. Probiotics reduced hyperandrogenism, inflammatory and oxidative conditions, and resulted more effective when combined with selenium. Although these results proved to be satisfactory, further studies are needed with larger samples and a more homogeneous analysis of the outcomes.

Mennen, F. E., et al. (2021). "Effectiveness of an Interpersonal Psychotherapy (IPT) Group Depression Treatment for Head Start Mothers: A Cluster-Randomized Controlled Trial." Journal of Affective Disorders 280(Pt B): 39-48.
	BACKGROUND: Maternal depression is known to be a serious problem with higher rates among poor and racial/ethnic minority mothers that can have numerous negative impacts on their children. These mothers have less access to effective care and may be wary of traditional mental health care because of the stigma. The purpose of this study was to test whether an adaptation of an Interpersonal Psychotherapy group for perinatal depression could be effective in reducing depressive symptoms of mothers whose children were enrolled in Head Start. METHODS: Forty-nine mothers, randomized by site, were recruited into the intervention group, 70 into the control group. They were measured on depressive symptoms, parenting stress, parenting behavior, and parent child interaction at intake, at end of the group, and 6 months following. RESULTS: The intervention group was lower in depressive symptoms at the end of treatment with a further decrease 6 months post intervention. There was no change in the control group. The intervention group also improved in parenting stress. LIMITATIONS: The sample size for the intervention group was smaller than desired. CONCLUSIONS: This study supports the effectiveness of this 12 session IPT group which was highly effective for a population of Head Start mothers. It is a strategy that can be adapted to other settings that serve low income mothers.

Menon, U., et al. (2023). "Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial." The Lancet. Oncology 24(9): 1018-1028.
	Background: In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy.; Methods: UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50-74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to-screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032.; Findings: 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0·5%) of 50 625 participants in the multimodal screening group and 520 (0·5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0·0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0·0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0·0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0·0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0·69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9·51 years (IQR 6·04-13·00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6·9% (95% CI 0·4-13·0; p=0·042) at 18 years (21% [95% CI 15·6-26·2] vs 14% [95% CI 10·5-17·4]).; Interpretation: To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer.; Funding: National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal.; Competing Interests: Declaration of interests UM had stock ownership, awarded by University College London (UCL) until October, 2021, in Abcodia, which holds the licence for risk of ovarian cancer algorithm (ROCA). UM and MKBP have received grants and AG-M, AR, SA, and MB have been funded by grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), and The Eve Appeal. UM has also received grants from the Australian National Health and Medical Research Council (NHMRC) and salary support from University College London Hospitals Biomedical Research Centre. UM, AG-M, and SA report research collaboration contracts with Cambridge University, QIMR Berghof r Medical Research Institute, Intelligent Lab on Fiber, RNA Guardian, Micronoma, MercyBio Analytics, Imperial College London, University of Innsbruck, and Dana Farber USA. UM holds patent number EP10178345.4 for Breast Cancer Diagnostics. UM received an honorarium for a lecture from the New York Obstetrical Society (USA), and was reimbursed for travel by New York Obstetrical Society, US National Cancer Policy Forum, and Robinson College, Cambridge, UK. UM is a member of Tina's Wish Scientific Advisory Board (USA) and Research Advisory Panel, Yorkshire Cancer Research (UK). She has been a member of International Alliance for Cancer Early Detection (ACED); data monitoring committee for the mixed COVID-19 vaccines study in India; Good Clinical Practice Professional Certification Scheme steering committee, CDSA, India; Clinical and Public Health Fellowship Selection Committee, Wellcome Trust DBT India Alliance; Prevention Expert Review Panel, Population Research Committee, Cancer Research UK; and chair of the data monitoring committee for GEM3. AG-M is a member of ACED Gynaecological Cancer Working Group and is ACED codirector Research Domain Trials. MKBP was an Associate Member of the EME funding committee while the project was active. SA reports funding to UCL from Abcodia between 2011 and 2020. SJS codeveloped ROCA in 1995, which was patented by Massachusetts General Hospital, MA, USA, and Queen Mary University of London, London, UK, and is owned by these universities (the patent has expired). Massachusetts General Hospital and Queen Mary University of London granted a licence for the ROCA to Abcodia in 2014. SJS reports stock options from SISCAPA Assay Technologies for participation on a board and from the US National Cancer Institute, NIHR, and Mercy Bioanalytics. SJS participated in the independent data monitoring committee for GRAIL, and served on the clinical advisory board for Guardant Health (for which he was paid consulting fees), and on the Scientific Advisory Board for LUNGevity. SJS also has a collaboration agreement with Freenome. IJJ reports grants from Eve Appeal Charity, MRC, Cancer Research UK, and NIHR during the conduct of the study. IJJ coinvented the ROCA in 1995. Massachusetts General Hospital and Queen Mary University of London granted a licence for the ROCA to Abcodia in 2014. IJJ is non-executive director, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. IJJ founded (in 1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. LF reports MRC funding for the psychosocial group of the UKCTOCS study 2001–13, paid to University of Sussex. NS received honoraria from AstraZeneca–MSD and GSK for participation in advisory boards. AJM was a member of NIHR Health Technology Assessment and Efficacy and Mechanism Evaluation editoral board (2012–22). RM reports funding from The Eve Appeal, Rosetrees Trust, Barts Charity, Yorkshire Cancer Research, Ovacure, British Gynaecological Cancer Society, AstraZeneca, and GSK. All other authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Menon, U., et al. (2021). "Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial." Lancet (London, England) 397(10290): 2182-2193.
	BACKGROUND: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. METHODS: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. INTERPRETATION: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. FUNDING: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.

Menown Sara, J. and A. Tello Javier (2021). "Neurokinin 3 Receptor Antagonists Compared With Serotonin Norepinephrine Reuptake Inhibitors for Non-Hormonal Treatment of Menopausal Hot Flushes: A Systematic Qualitative Review." Advances in Therapy 38(10): 5025-5045.
	Introduction: Hot flushes/flashes (HFs) or other vasomotor symptoms affect between 45 and 97% of women during menopause. Hormone replacement therapy (HRT) is effective at alleviating menopausal symptoms, but some women cannot or prefer not to take HRT. Since current non-hormonal options have suboptimal efficacy/tolerability, there is a pressing need for an effective, well-tolerated alternative. The neurokinin 3 receptor (NK3R) has recently been implicated in the generation of menopausal HFs and represents a novel therapeutic target to ameliorate HF symptoms. This review aims to assess if NK3R antagonists (NK3Ras) are more effective than Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)-currently a common choice for non-hormonal treatment of menopausal HFs.; Methods: Studies were identified after systematically searching Ovid MEDLINE and EMBASE databases based on PRISMA guidelines. Trial quality and bias were assessed. Key efficacy outcomes (HF frequency, HF severity and number of night-time awakenings/night-sweats) and selected safety outcomes were extracted and analysed.; Results: Seven SNRI and four NK3Ra placebo-controlled randomised trials (plus four follow-up reports) were included in this review. NK3Ra administration resulted in a larger reduction from baseline in HF frequency, HF severity and night-sweats compared to SNRIs. Five of seven SNRI trials showed a reduction in HF frequency that was statistically significant (by 48-67% from baseline at weeks 8 or 12) whereas all NK3Ra trials showed a statistically significant reduction in HF frequency (by 62-93% from baseline at weeks 2, 4 or 12). While SNRI trials reported poor tolerability, particularly nausea, NK3Ra trials reported good tolerability overall, although two trials reported elevation in transaminases.; Conclusion: NK3Ras trials show encouraging efficacy and tolerability/safety. Completion of phase 3 NK3Ra trials are required to confirm efficacy and uphold safety/tolerability data but phase 2 results suggest that NK3Ras are more effective than SNRIs for non-hormonal treatment of menopausal HFs. (© 2021. The Author(s).)

Menshawey, E. and R. Menshawey (2022). "Laparoscopic Assisted Vaginal Hysterectomy Verses Abdominal Hysterectomy: A systematic review and metanalysis." MedRxiv.
	OBJECTIVE: To examine studies that explored the differences between laparoscopic assisted vaginal hysterectomy (LAVH) and total abdominal hysterectomy (TAH) in endometrial cancer (EC) patients, and to determine which surgical intervention has better outcomes. DATA SOURCES: Electronic search of the following databases was performed; Google Scholar, PubMed/Medline, Wiley, Web of Science, Cochrane Library, Embase, and EBSCO Host. METHODS of STUDY SELECTION: All full English articles in the form of randomized controlled trials (RCT), prospective cohort (PC), and retrospective cohort (RC) comparing LAVH and TAH outcomes in endometrial cancer patients was included in this study. A complete search of the literature comparing the outcomes of LAVH and AH in EC patients. This study was registered in PROSPERO [ID: CRD42021225509] and follows PRISMA and MOOSE guidelines. Outcomes included length of hospital stay, surgical duration, complications, blood transfusion requirements, and blood loss. TABULATION: ROBINS-1, ROB 2.0, and ROBVIS was used to assess the risk of bias. Statistical tests used included relative risk (RR) for dichotomous and standard mean difference (SMD) for continuous variable. A P value less than 0.05 was considered significant. A forest plot was used to visually demonstrate the analyses for all outcomes. INTEGRATION and RESULTS: A total of 13 articles (total cohort n=14,803) were included in the systematic review and metanalysis. The total cohort for LAVH patients was n=1845 and n=12,958 for TAH. Patients who underwent a TAH had significantly higher risk of complications [RR = 0.547, p<0.001], greater risk for blood transfusion [RR = 0.349, p<0.033], more blood loss [SMD = -3.256, p<0.001], and longer hospital stay [SMD = -1.351, p<0.001]. LAVH patients had longer operating time [SMD= 1.103, p<0.001] compared TAH patients. CONCLUSION(S): LAVH presented with lower of hospital stay, complications, amount of blood loss, and blood transfusion requirements when compared to TAH. LAVH in the appropriate setting and skills may be a safer alternative than TAH.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Mension, E., et al. (2022). "Vaginal laser therapy for genitourinary syndrome of menopause - systematic review." Maturitas 156: 37-59.
	Background: Genitourinary syndrome of menopause (GSM) can have a great impact on the quality of life (QOL), and affects between 53.8% and 90% of postmenopausal women. The literature suggests that vaginal laser therapy could be an effective treatment for GSM symptoms, but its efficacy and safety have not been established and international societies do not endorse its use. Despite that, there has been an increase in the use of vaginal laser therapy globally over the last decade.; Objective: The objective of this review is to evaluate the literature which assesses the efficacy and safety of the vaginal laser therapy in the treatment of GSM.; Methods: A comprehensive literature search was conducted electronically using Embase and PubMed to retrieve studies assessing evidence for the efficacy and safety of vaginal laser therapy for GSM or vulvovaginal atrophy up to June 2021.; Results: A total of 64 studies were finally included in the review. There were 10 controlled intervention studies, 7 observational cohort and cross-sectional studies and 47 before-after studies without a control group.; Conclusion: Vaginal laser seems to improve scores on the Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI) and Vaginal Health Index (VHI) in GSM over the short term. Safety outcomes are underreported and short-term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Meriwether Kate, V., et al. (2019). "Uterine-preserving surgeries for the repair of pelvic organ prolapse: a systematic review with meta-analysis and clinical practice guidelines." International Urogynecology Journal 30(4): 505-522.
	Introduction and Hypothesis: We aimed to systematically review the literature on pelvic organ prolapse (POP) surgery with uterine preservation (hysteropexy). We hypothesized that different hysteropexy surgeries would have similar POP outcomes but varying adverse event (AE) rates.; Methods: MEDLINE, Cochrane, and clinicaltrials.gov databases were reviewed from inception to January 2018 for comparative (any size) and single-arm studies (n ≥ 50) involving hysteropexy. Studies were extracted for participant characteristics, interventions, comparators, outcomes, and AEs and assessed for methodological quality.; Results: We identified 99 eligible studies: 53 comparing hysteropexy to POP surgery with hysterectomy, 42 single-arm studies on hysteropexy, and four studies comparing stage ≥2 hysteropexy types. Data on POP outcomes were heterogeneous and usually from <3 years of follow-up. Repeat surgery prevalence for POP after hysteropexy varied widely (0-29%) but was similar among hysteropexy types. When comparing sacrohysteropexy routes, the laparoscopic approach had lower recurrent prolapse symptoms [odds ratio (OR) 0.18, 95% confidence interval (CI) 0.07-0.46), urinary retention (OR 0.05, 95% CI 0.003-0.83), and blood loss (difference -104 ml, 95% CI -145 to -63 ml) than open sacrohysteropexy. Laparoscopic sacrohysteropexy had longer operative times than vaginal mesh hysteropexy (difference 119 min, 95% CI 102-136 min). Most commonly reported AEs included mesh exposure (0-39%), urinary retention (0-80%), and sexual dysfunction (0-48%).; Conclusions: Hysteropexies have a wide range of POP recurrence and AEs; little data exist directly comparing different hysteropexy types. Therefore, for women choosing uterine preservation, surgeons should counsel them on outcomes and risks particular to the specific hysteropexy type planned.

Merlo, S., et al. (2022). "Survival in patients with advanced staged epithelial ovarian cancer: is treatment with neoadjuvant chemotherapy more effective than primary debulking surgery?" Zdravniski Vestnik 91(1-2): 3-13.
	Background: The aim of this research was to evaluate the superiority or non-inferiority of neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) in the management of patients with advanced-stage epithelial ovarian carcinoma. Method(s): The study evaluated consecutive patients with advanced-stage (FIGO stage IIIC/IV) ovarian cancer treated at the Institute of Oncology institute Ljubljana from 01/01/ January 2005 to 31/12/ December 2015. The study tried to determine whether PDS and adjuvant chemotherapy compared to NACT and interval debulking surgery are equivalent management of patients with advanced epithelial ovarian cancer, in regard to overall survival (OS), 5-year survival, progression-free survival and resection rates. Result(s): Three hundred and two women met the inclusion criteria, 84.1% (254/302) were treated with NACT and 15.9% (48/302) with PDS. Median age was 61 years (range 29-85). The median OS was lower in the NACT group compared to PDS group, i.e. 24 months and vs. 52 months, respectively. The PFS in NACT group was 9 months in NACT group and 19 months in PDS group. Five-year survival rate was 35% Iin patients treated with PDS 5-year survival rate was 35% and 15% in NACT group. In patients with complete gross resection treated with PDS median OS was 54 months compared to 36 months in patients treated with NACT and complete gross resection in IDS. Complete gross resection was achieved in 35.4% in PDS group and in 52.4% in NACT group.Copyright © 2022 Slovenian Medical Journal.

Merlot, B., et al. (2022). "Pain Reduction With an Immersive Digital Therapeutic Tool in Women Living With Endometriosis-Related Pelvic Pain: Randomized Controlled Trial." Journal of Medical Internet Research 24(9): e39531.
	Background: Chronic pelvic pain is a common and disabling condition in women living with endometriosis. Pharmacological and surgical treatments are not always effective at controlling pain and present important restrictions. Digital therapeutics (DTx) are emerging as major nonpharmacological alternatives that aim to extend the analgesic therapeutic arsenal of patients.; Objective: In this randomized controlled trial (RCT), we aimed to measure the immediate and 4-hour persisting effects of a single use 20-minute DTx (Endocare) on pain in women experiencing pelvic pain due to endometriosis.; Methods: A total of 45 women with endometriosis participated in a randomized controlled study comparing the analgesic effect of a single use of a virtual reality digital treatment named Endocare (n=23, 51%) to a 2D digital control (n=22, 49%). Perceived pain and pain relief were measured before the treatment and 15, 30, 45, 60, and 240 minutes after the end of the treatment.; Results: The clustered posttreatment pain was significantly reduced compared to the pretreatment for both Endocare and the control group (all P<.01). Endocare was significantly more effective than the control group (all P<.01). Endocare decreased the mean pain intensity from 6.0 (SD 1.31) before the treatment to 4.5 (SD 1.71) posttreatment, while the control only decreased it from 5.7 (SD 1.36) to 5.0 (SD 1.43). When comparing each posttreatment measures to the pretest, Endocare significantly reduced pain perception for all points in time up to 4 hours posttreatment. The differences did not reached significance for the control group. Moreover, Endocare was significantly superior to the control group 15, 30, and 45 minutes after the treatment (all P<.001). The mean perceived pain relief was significantly higher for Endocare at 28% (SD 2%) compared to the control, which was 15% (SD 1%) for all the posttreatment measurements (all P>.05).; Conclusions: Our study aimed to test the effects of a single use of a DTx treatment on reported pain at different time points in women diagnosed with endometriosis experiencing moderate-to-severe pelvic pain. Importantly, our results support that Endocare, a virtual reality immersive treatment, significantly reduce pain perception compared to a digital control in women living with endometriosis. Interestingly, we are the first to notice that the effect persisted up to 4 hours posttreatment.; Trial Registration: ClinicalTrials.gov NCT04650516; https://tinyurl.com/2a2eu9wv. (©Benjamin Merlot, Garance Dispersyn, Zoé Husson, Isabella Chanavaz-Lacheray, Thomas Dennis, Juliette Greco-Vuilloud, Maxime Fougère, Stéphane Potvin, Maryne Cotty-Eslous, Horace Roman, Serge Marchand. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.09.2022.)

Merlot, B., et al. (2023). "Pain Reduction With an Immersive Digital Therapeutic in Women Living With Endometriosis-Related Pelvic Pain: At-Home Self-Administered Randomized Controlled Trial." Journal of Medical Internet Research 25: e47869.
	Background: The management of chronic pelvic pain in women with endometriosis is complex and includes the long-term use of opioids. Patients not fully responsive to drugs or ineligible for surgical treatments need efficient alternatives to improve their quality of life and avoid long-term sequelae.; Objective: This randomized controlled trial aimed to assess the effects of repeated at-home administrations of a 20-minute virtual reality (VR) solution (Endocare) compared with a sham condition on pain in women experiencing pelvic pain due to endometriosis.; Methods: Patients were instructed to use the VR headsets twice daily for at least 2 days and for up to 5 days starting on their first day of painful periods. Pain perception was measured using a numerical scale (0-10) before and 60, 120, and 180 minutes after each treatment administration. General pain, stress, fatigue, medication intake, and quality of life were reported daily by patients.; Results: A total of 102 patients with endometriosis were included in the final analysis (Endocare group: n=51, 50%; sham group: n=51, 50%). The mean age was 32.88 years (SD 6.96) and the mean pain intensity before treatment was 6.53 (SD 1.74) and 6.22 (SD 1.69) for the Endocare group and the sham control group, respectively (P=.48). Pain intensity decreased in both groups from day 1 to day 5 along with a decrease in medication use. Maximum pain intensity reduction of 51.58% (SD 35.33) occurred at day 2, 120 minutes after treatment for the Endocare group and of 27.37% (SD 27.23) at day 3, 180 minutes after treatment for the control group. Endocare was significantly superior to the sham on day 1 (120 minutes, P=.04; 180 minutes, P=.001), day 2 (0 minutes, P=.02; 60, 120, and 180 minutes, all P<.001), and day 3 (60 minutes, P=.01; 120 minutes, P=.005; 180 minutes, P=.001). Similarly, the mean perceived pain relief was significantly higher with Endocare on day 1 (120 and 180 minutes P=.004 and P=.001, respectively) and day 2 (60, 120, and 180 minutes P=.003, P=.004, and P=.007, respectively) compared to the control. No adverse event was reported.; Conclusions: This study confirmed the effectiveness and safety of self-repeated administrations of a VR immersive treatment used at home while reducing overall pain medication intake in women diagnosed with endometriosis experiencing moderate-to-severe pelvic pain.; Trial Registration: ClinicalTrials.gov NCT05172492; https://clinicaltrials.gov/ct2/show/NCT05172492. (©Benjamin Merlot, Valéry Elie, Adrien Périgord, Zoé Husson, Amandine Jubert, Isabella Chanavaz-Lacheray, Thomas Dennis, Maryne Cotty-Eslous, Horace Roman. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.06.2023.)

Merlot, B., et al. (2023). "Pain Reduction With an Immersive Digital Therapeutic in Women Living With Endometriosis-Related Pelvic Pain: At-Home Self-Administered Randomized Controlled Trial." Journal of Medical Internet Research 25: e47869.
	Background The management of chronic pelvic pain in women with endometriosis is complex and includes the long-term use of opioids. Patients not fully responsive to drugs or ineligible for surgical treatments need efficient alternatives to improve their quality of life and avoid long-term sequelae. Objective This randomized controlled trial aimed to assess the effects of repeated at-home administrations of a 20-minute virtual reality (VR) solution (Endocare) compared with a sham condition on pain in women experiencing pelvic pain due to endometriosis. Methods Patients were instructed to use the VR headsets twice daily for at least 2 days and for up to 5 days starting on their first day of painful periods. Pain perception was measured using a numerical scale (0-10) before and 60, 120, and 180 minutes after each treatment administration. General pain, stress, fatigue, medication intake, and quality of life were reported daily by patients. Results A total of 102 patients with endometriosis were included in the final analysis (Endocare group: n=51, 50%; sham group: n=51, 50%). The mean age was 32.88 years (SD 6.96) and the mean pain intensity before treatment was 6.53 (SD 1.74) and 6.22 (SD 1.69) for the Endocare group and the sham control group, respectively (P=.48). Pain intensity decreased in both groups from day 1 to day 5 along with a decrease in medication use. Maximum pain intensity reduction of 51.58% (SD 35.33) occurred at day 2, 120 minutes after treatment for the Endocare group and of 27.37% (SD 27.23) at day 3, 180 minutes after treatment for the control group. Endocare was significantly superior to the sham on day 1 (120 minutes, P=.04; 180 minutes, P=.001), day 2 (0 minutes, P=.02; 60, 120, and 180 minutes, all P<.001), and day 3 (60 minutes, P=.01; 120 minutes, P=.005; 180 minutes, P=.001). Similarly, the mean perceived pain relief was significantly higher with Endocare on day 1 (120 and 180 minutes P=.004 and P=.001, respectively) and day 2 (60, 120, and 180 minutes P=.003, P=.004, and P=.007, respectively) compared to the control. No adverse event was reported. Conclusions This study confirmed the effectiveness and safety of self-repeated administrations of a VR immersive treatment used at home while reducing overall pain medication intake in women diagnosed with endometriosis experiencing moderate-to-severe pelvic pain. Trial Registration ClinicalTrials.gov NCT05172492; https://clinicaltrials.gov/ct2/show/NCT05172492

Merriman, A. L., et al. (2024). "Barbed Versus Nonbarbed Suture for Posterior Colporrhaphy: A Randomized Controlled Trial." Urogynecology (Philadelphia, Pa.).
	IMPORTANCE: There is limited literature or even consensus on the suture material used for posterior vaginal repairs. OBJECTIVE(S): This study aimed to compare outcomes of barbed versus nonbarbed delayed absorbable suture used for posterior colporrhaphy. STUDY DESIGN: This study conducted a randomized controlled trial of 72 women undergoing posterior repair using standardized technique-concurrent procedures permitted with barbed (n = 36) or nonbarbed (n = 36) suture. Standardized examinations, validated questionnaires, and a visual analog scale (VAS) were completed at baseline, 6 weeks, and 12 months, and a telephone interview was conducted at 6 months. The primary outcome was posterior compartment pain at 6 weeks, measured by a VAS. RESULT(S): Seventy-two women enrolled, with follow-up rates 6 weeks (100%), 6 months (90.3%), and 12 months (73.6%). Demographics were similar between groups. A VAS with movement was not different between groups at 6 weeks. The odds of experiencing vaginal pain, having myofascial pain on examination, or being sexually active postoperatively were not different between the groups. There were no differences in the length of posterior colporrhaphy, surgical times, or hospital length of stay between the groups. Suture passes were lower in the nonbarbed group (median, 4 vs 7; P = <0.001), and suture burden was higher in the nonbarbed group (median, 26.9 vs 10.5 cm; P = <0.001). There was overall improvement in Pelvic Floor Distress Inventory Short Form 20 prolapse and colorectal subscores but no differences between groups. Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form 12 scores improved, and dyspareunia decreased at 6 and 12 months in both groups. In addition, there were few anatomic recurrences at 6 weeks (0%) and 12 months (3.4%) and few adverse events. CONCLUSION(S): This study found no differences in primary or secondary outcomes; however, both suture types resulted in clinical improvements in quality-of-life measures and sexual function.Copyright © 2024 American Urogynecologic Society. All rights reserved.

Merviel, P., et al. (2021). "Xanthogranulomatous endometritis: A case report and literature review." Clinical case reports 9(6): e04299.
	Xanthogranulomatous endometritis is a rare benign pathology mimicking endometrial carcinoma.

Merza, D., et al. (2024). "Online peer-delivered group cognitive-behavioral therapy for postpartum depression: A randomized controlled trial." Acta Psychiatrica Scandinavica 150(5): 422-432.
	BACKGROUND: Postpartum depression (PPD) affects up to one in five mothers and birthing parents, yet just 10% receive evidence-based care. This randomized controlled trial aimed to determine if a synchronous online 9-week group cognitive-behavioral therapy (CBT) intervention delivered by mothers who have recovered from postpartum depression (i.e., peers) could effectively improve PPD and its comorbidities. METHODS: Participants (n = 183) in this study lived in Ontario, Canada, were ≥18 years-old, had an infant <12 months, were fluent in English, and scored ≥10 on the Edinburgh Postnatal Depression Scale (EPDS). They were randomized to experimental (received intervention plus treatment as usual (TAU)) or waitlist control (TAU plus the intervention after a 9-week wait) groups. Depression, anxiety, social support, mother-infant bonding, and infant temperament were assessed at baseline and 9 weeks later. Outcomes were assessed in the experimental group 3 months post-intervention to assess stability. RESULTS: Statistically significant reductions were observed in EPDS (B = 5.99; p < 0.001; d = 1.32) and Generalized Anxiety Disorder Questionnaire-7 scores (B = 5.94; p < 0.001; d = 1.22), improvements that remained stable 3 months post-intervention in the experimental group. Maternal social support (p = 0.02; d = 0.40), infant-focused anxiety (p = 0.02; d = 0.54), and infant negative emotionality (p < 0.01; d = 0.23) also improved post-intervention and remained stable 3 months later. CONCLUSION: Online peer-delivered group CBT for PPD can effectively treat PPD and anxiety, and improve social support, infant-focused anxiety, and negative emotionality in infants. This intervention could provide the means to increase access to treatment for those experiencing PPD and improve outcomes for mothers, birthing parents, and families.

Mesdaghinia, E., et al. (2021). "The effects of zinc supplementation on clinical response and metabolic profiles in pregnant women at risk for intrauterine growth restriction: a randomized, double-blind, placebo-controlled trial." Journal of maternal-fetal & neonatal medicine 34(9): 1382‐1388.
	OBJECTIVE: This investigation was conducted to assess the effects of zinc supplementation on clinical response and metabolic status among pregnant women at risk for intrauterine growth restriction (IUGR). METHODS: This randomized, double‐blind, placebo‐controlled, clinical trial was conducted among 52 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to take either 233 mg zinc gluconate (containing 30 mg zinc) supplements (n = 26) or placebo (n = 26) for 10 weeks from 17 to 27 weeks of gestation. Fasting blood samples were taken at baseline and after the 10‐week treatment to quantify related variables. RESULTS: After the 10‐week intervention, taking zinc led to a significant reduction in serum high‐sensitivity C‐reactive protein (hs‐CRP) (β ‒1.17 mg/L; 95% CI, ‐1.77, ‐0.57; p < .001) and plasma malondialdehyde (MDA) levels (β ‐0.23 µmol/L; 95% CI, ‐0.45, ‐0.02; p = .03); also a significant rise in total antioxidant capacity (TAC) (β 59.22 mmol/L; 95% CI, 25.07, 93.36; p = .001) was observed in comparison to placebo. In addition, zinc supplementation significantly reduced serum insulin (β ‐1.33 µIU/mL; 95% CI, ‐2.00, ‐0.67; p < .001) and insulin resistance (β ‐0.30; 95% CI, ‐0.44, ‐0.15; p < .001), and significantly increased insulin sensitivity (β 0.008; 95% CI, 0.003, 0.01; p < .001) compared with the placebo. Zinc supplementation did not influence pulsatility index (PI) and other metabolic parameters. CONCLUSIONS: Overall, zinc supplementation in pregnant women at risk for IUGR had beneficial effects on TAC, MDA, hs‐CRP, and insulin metabolism, but did not affect PI and other metabolic profiles.

Meshaal, H., et al. (2022). "Hysteroscopic management versus ultrasound-guided evacuation for women with first-trimester pregnancy loss, a randomised controlled trial." BMC Women's Health 22(1): 190.
	Objective: We aimed to evaluate the hysteroscopic management of first-trimester pregnancy loss compared to surgical evacuation either blind or under ultrasonographic guidance. Method(s): This clinical trial included 315 women with first-trimester pregnancy loss, divided equally into three groups. Group 1 underwent traditional blind surgical evacuation, group 2 underwent ultrasound-guided evacuation, and group 3 underwent hysteroscopic management. All women were assessed for retained products, surgical complications, the need for further management, and pregnancy occurrence after evacuation within 2 years of follow up. Result(s): The rate of presence of conception remnants and the need for further treatment was significantly higher in group 1 compared to groups 2 and 3 (4.8% vs. 0% vs. 0%, P = 0.012). The conception rate within 2 years was significantly lower in group 1 compared to groups 2 and 3 (57.4% vs. 73.2% vs. 82.7%, P = 0.002), and the duration needed to conceive was significantly prolonged in group 1 compared to groups 2 and 3 (9.8 vs. 8.3 vs. 6.9 months, P < 0.001). Interestingly, women who underwent hysteroscopic management needed a significantly shorter time to conceive than those who underwent ultrasound-guided evacuation (6.9 vs. 8.3 months, P = 0.006). Conclusion(s): Hysteroscopic management of first-trimester pregnancy loss was superior to ultrasound-guided surgical evacuation regarding the time interval to conceive. Both techniques were superior to the blind evacuation technique regarding removal of the whole conception remnants, need for further treatment and fertility outcomes. Clinical trial registration: It was first registered at ClinicalTrials.gov on16/03/2017 with registration number NCT03081104.Copyright © 2022, The Author(s).

Metaxas, Y., et al. (2022). "A phase I trial of lurbinectedin in combination with cisplatin in patients with advanced solid tumors." Investigational New Drugs 40(1): 91-98.
	Background In vitro/in vivo data showed synergism of cisplatin and lurbinectedin in ovarian cancer cells and grafts. This phase I trial investigated the recommended phase II dose (RD) of cisplatin and lurbinectedin combination, with (Group A) or without aprepitant (Group B), in patients with advanced solid tumors. Patients and Methods All patients received 60 mg/m 2 cisplatin 90-min intravenous (i.v.) infusion followed by lurbinectedin 60-min i.v. infusion at escalating doses on Day 1 every 3 weeks (q3wk). Patients in Group A additionally received orally 125 mg aprepitant one hour before cisplatin on Day 1 and 80 mg on Days 2 and 3. Toxicity was graded according to the NCI-CTCAE v.4. Results RD for Group A was cisplatin 60 mg/m 2 plus lurbinectedin 1.1 mg/m 2 . RD for Group B was cisplatin 60 mg/m 2 plus lurbinectedin 1.4 mg/m 2 . The most frequent grade ≥ 3 adverse events were hematological [neutropenia (41%), lymphopenia (35%), leukopenia (24%), thrombocytopenia (18%)] and fatigue (35%) in Group A (n = 17), and neutropenia (50%), leukopenia (42%), lymphopenia (29%), and fatigue (13%) and nausea (8%) in Group B (n = 24). Four patients (2 in each group) had a partial response. Disease stabilization for ≥ 4 months was observed in 4 and 10 patients, respectively. Conclusion The combination of lurbinectedin with cisplatin was not possible in meaningful therapeutic dosage due to toxicity. The addition of aprepitant in combination with cisplatin did not allow increasing the dose due to hematological toxicity, whereas omitting aprepitant increased the incidence of nausea and vomiting. Modest clinical activity was observed in general.Clinical trial registration www.ClinicalTrials.gov code: NCT01980667. Date of registration: 11 November 2013. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metoyer, A. and V. Nagin (2022). "Exercise parameters for treatment of stress urinary incontinence in women's health physical therapy: A systematic review." Dissertation Abstracts International: Section B: The Sciences and Engineering 83(6-B): No-Specified.
	Background: Stress urinary incontinence (SUI) is a common side effect of vaginal childbirth that can be treated with exercise. There is not a consensus on what specific exercise parameters are needed to treat stress urinary incontinence. Purpose: The purpose of this systematic review is to utilize the Modified CERT as a tool to determine the most appropriate and effective exercises, including parameters such as dose, intensity, and frequency, for pelvic floor physical therapy programs and home exercise programs (HEPs) for women who are less than 12 months postpartum experiencing SUI. Study Design: The design of this study is a systematic literature review. Methods: MEDLINE complete, CINAHL complete, SPORT Discus, and Academic Search Complete databases were searched to determine the appropriateness of the articles for this study. The study population included postpartum women ages 18 to 45 who suffered from stress urinary incontinence due to childbirth and were treated using physical therapy exercise to decrease symptoms. The PEDro scale was used to determine the risk of bias for the randomized controlled trials utilized in this study. Results: A total of five articles were reviewed for this study. Strength and endurance Kegels were found to be the most effective treatment to reduce SUI symptoms. Researchers found that in-person exercise programs were more effective in treating SUI symptoms than HEPs. Discussion: Pelvic floor strengthening and endurance exercises improved quality of life and decreased symptoms. Incorporating HEPs was beneficial when researchers followed up with participants frequently and in person. Future research is needed to determine the effectiveness of exercise prescription due to only one of the articles included in this study utilizing an individualized exercise program. Conclusion: Pelvic floor strengthening and endurance exercises are the most effective when treating postpartum women suffering from SUI. In-person and home exercise programs should be utilized to improve adherence to the patients' plan of care. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Metwally, M., et al. (2021). "A randomised controlled trial to assess the clinical effectiveness and safety of the endometrial scratch procedure prior to first-time IVF, with or without ICSI." Human reproduction (Oxford, England) 36(7): 1841-1853.
	STUDY QUESTION: What is the clinical-effectiveness and safety of the endometrial scratch (ES) procedure compared to no ES, prior to usual first time in vitro fertilisation (IVF) treatment? SUMMARY ANSWER: ES was safe but did not improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF cycle, with or without intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ES is an 'add-on' treatment that is available to women undergoing a first cycle of IVF, with or without ICSI, despite a lack of evidence to support its use. STUDY DESIGN, SIZE, DURATION: This pragmatic, superiority, open-label, multi-centre, parallel-group randomised controlled trial involving 1048 women assessed the clinical effectiveness and safety of the ES procedure prior to first time IVF, with or without ICSI, between July 2016 and October 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants aged 18-37 years undergoing their first cycle of IVF, with or without ICSI, were recruited from 16 UK fertility clinics and randomised (1:1) by a web-based system with restricted access rights that concealed allocation. Stratified block randomisation was used to allocate participants to TAU or ES in the mid-luteal phase followed by usual IVF with or without ICSI treatment. The primary outcome was live birth after completing 24 weeks gestation within 10.5 months of egg collection. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1048 women randomised to TAU (n = 525) and ES (n = 523) were available for intention to treat analysis. In the ES group, 453 (86.6%) received the ES procedure. IVF, with or without ICSI, was received in 494 (94.1%) and 497 (95.0%) of ES and TAU participants respectively. Live birth rate was 37.1% (195/525) in the TAU and 38.6% (202/523) in the ES: an unadjusted absolute difference of 1.5% (95% CI -4.4% to 7.4%, P = 0.621). There were no statistical differences in secondary outcomes. Adverse events were comparable across groups. LIMITATIONS, REASONS FOR CAUTION: A sham ES procedure was not undertaken in the control group, however, we do not believe this would have influenced the results as objective fertility outcomes were used. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest trial that is adequately powered to assess the impact of ES on women undergoing their first cycle of IVF. ES was safe, but did not significantly improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF or ICSI cycle. We recommend that ES is not undertaken in this population. STUDY FUNDING/COMPETING INTEREST(S): Funded by the National Institute of Health Research. Stephen Walters is an National Institute for Health Research (NIHR) Senior Investigator (2018 to present) and was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2011-2017), NIHR HTA Commissioning Strategy Group (2012 to 2017); NIHR Programme Grants for Applied Research Committee (2020 to present); NIHR Pre doctoral Fellowship Committee (2019 to present). Dr. Martins da Silva reports grants from AstraZeneca, during the conduct of the study; and is Associate editor of Human Reproduction and Editorial Board member of Reproduction and Fertility. Dr. Bhide reports grants from Bart's Charity and grants and non-financial support from Pharmasure Pharmaceuticals outside the submitted work. TRIAL REGISTRATION NUMBER: ISRCTN number: ISRCTN23800982. TRIAL REGISTRATION DATE: 31 May 2016. DATE OF FIRST PATIENT’S ENROLMENT: 04 July 2016.

Meyer, I., et al. (2023). "Five-year surgical outcomes of transvaginal apical approaches in women with advanced pelvic organ prolapse." International Urogynecology Journal 34(9): 2171-2181.
	Introduction and Hypothesis: In women with advanced prolapse, differences in vaginal apex anchoring sites may impact surgical outcomes over time. The primary aim was to compare 5-year surgical outcomes of uterosacral ligament suspension (ULS) versus sacrospinous ligament fixation (SSLF) in women with advanced (stage III-IV) prolapse.; Methods: A secondary analysis was conducted in a subset of women with advanced prolapse from a multicenter randomized trial comparing ULS versus SSLF and its extended follow-up, using publicly accessible de-identified datasets. The primary outcome was time to failure, defined as any one of (1) apical descent > 1/3 into the vaginal canal or anterior/posterior compartment beyond the hymen, (2) bothersome vaginal bulge symptoms, or (3) re-treatment. Secondary outcomes include symptom severity measured by the Pelvic Organ Prolapse Distress Inventory (POPDI) and adverse events.; Results: Of 285 women, 90/147 (61.2%) in ULS and 88/138 (63.8%) in SSLF had advanced prolapse. Baseline characteristics did not differ between groups except for median-vaginal deliveries (3.0 [2.0, 5.0] versus 3.0 [2.0, 4.0], p < 0.01). The median time to failure was 1.7 years ULS versus 2.0 years SSLF (p = 0.42). Surgical failure increased over time in both groups with no intergroup difference; by year 5, the estimated failure rate was 67.7% ULS versus 71.5% SSLF (adjusted difference -3.8; 95%CI [-21.9, 14.2]). No differences were noted in individual failure components (p > 0.05). POPDI scores improved over 5 years without intergroup difference (ULS -68.0 ± 61.1 versus SSLF -69.9 ± 60.3, adjusted difference -0.1 [-20.0, 19.9]). No difference in adverse events were observed (p > 0.05).; Conclusion: In women with advanced prolapse, surgical failure, symptom severity, and adverse events did not differ between ULS and SSLF over 5 years. (© 2023. The International Urogynecological Association.)

Meyer, I., et al. (2021). "01 5-Year surgical outcomes of transvaginal apical approaches in women with advanced pelvic organ prolapse." American Journal of Obstetrics and Gynecology 224(6): S725.
	Objectives: To compare 5‐year surgical outcomes of uterosacral ligament suspension (ULS) versus (vs) sacrospinous ligament fixation (SSLF) in women with advanced pelvic organ prolapse (POP). Secondarily, to explore differences in outcomes between advanced vs stage II POP. Materials and Methods: A secondary analysis was conducted in a subset of women with advanced (stages III‐IV) POP from a multicenter randomized trial comparing (1) SSLF vs ULS and (2) perioperative behavioral with pelvic floor muscle training (BPMT) vs usual care. Publicly accessible de‐identified datasets of the index trial with 5‐year follow‐up were analyzed. The primary outcome was time to surgical failure, defined as (1) apical descent >1/3 into vaginal canal or anterior/posterior vaginal wall beyond the hymen, (2) bothersome vaginal bulge symptoms, or (3) retreatment (pessary or surgery) for POP. Secondary outcomes included symptom severity measured by the Pelvic Organ Prolapse Distress Inventory (POPDI), and adverse events (AEs). Outcomes in women with advanced stage POP were also compared to those with stage II POP. Results: Of 285 women in the index study, 90 of 147 (61.2%) in the ULS group and 88 of 138 (63.8%) in SSLF had advanced POP. Baseline characteristics did not differ between groups (mean age ULS = 61.0 ± 10.1 vs SSLF = 60.2 ± 9.9, P = 0.58). Surgical failure increased over 5 years in both groups with no intergroup difference (P = 0.42, Figure). By year 5, the estimated surgical failure rate was 67.7% for ULS vs 71.5% for SSLF (adjusted difference [a‐diff] = 3.8; 95% CI = 21.9, 14.2). No difference was noted in individual failure components (Figure); anatomic: 56.7% ULS vs 65.2% SSLF (a‐diff = 8.4; 95% CI = 28.0, 11.2), symptomatic: 38.8% ULS vs 43.1% SSLF (a‐diff = 4.3; 95% CI = 22.6, 14.1), retreatment: 20.0% USL vs 15.9% SSLF (a‐diff = 4.1; 95% CI = 9.4, 17.7). POPDI scores improved from baseline to 5 years in both groups without intergroup difference (ULS = 68.0 ± 61.1 vs SSLF = 69.9 ± 60.3, a‐diff = 0.1; 95% CI = 20.0, 19.9). AEs such as granulation tissue, suture exposure, and midurethral sling exposure did not differ over 5 years. Comparing women with advanced stages vs stage II POP, the estimated surgical failure did not differ over 5 years; 69.8% advanced vs 55.7% stage II (a‐diff = 14.1%; 95% CI = 33.7, 5.6). However, anatomic failure was higher in women with advanced POP (61.1% advanced vs 33.8% stage II, a‐diff = 27.3%; 95% CI = 47.5, ‐7.0). There was no difference in symptomatic failure (41.4% advanced vs 33.3% stage II, a‐diff = 8.1; 95% CI = 25.3, 9.1) or retreatment (11.7% advanced vs 8.0% stage II, a‐diff = 3.6; 95% CI = 12.0, 4.7). Conclusion: In women with advanced stage POP, surgical failure, symptom severity, and AEs did not differ between ULS and SSLF over 5 years. Compared to stage II POP, women with advanced POP had higher anatomic failure. [Formula presented]

Meyer, L. A., et al. (2021). "A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway." American Journal of Obstetrics and Gynecology 224(1): 70.e71-70.e11.
	BACKGROUND: Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours). OBJECTIVE: This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway. STUDY DESIGN: A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute-designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection. RESULTS: In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes. CONCLUSION: Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient's self-reported pain and functional recovery compared with standard bupivacaine.

Mhango, W., et al. (2023). "Psychoeducation as an active ingredient for interventions for perinatal depression and anxiety in youth: a mixed-method systematic literature review and lived experience synthesis." BJPsych Open 10(1): e10.
	Background: Psychoeducation is a common element in psychological interventions for youth depression and anxiety, but evidence about its use with youth perinatally is limited.; Aims: This review aims to understand outcomes and mechanisms of psychoeducation for the indicated prevention and treatment of perinatal depression and anxiety in youth.; Method: For this review, we synthesised published quantitative and qualitative evidence. Seven databases (ASSIA, Medline, PubMed, PsycINFO, PsycArticles, Scopus and Web of Science) were searched for studies published before 10 August 2021. We also had consultations with a youth advisory group ( N = 12).; Results: In total, 20 studies met the inclusion criteria. Seven quantitative studies examined multicomponent interventions that included psychoeducation, and one study evaluated psychoeducation as a standalone intervention for postnatal depression. Multicomponent interventions showed significant effects on postnatal depression in two out of six studies, as well as being effective at reducing prenatal anxiety in one study. Standalone psychoeducation for postnatal depression was also effective in one study. Evidence from 12 qualitative studies, corroborated by commentaries from the youth advisory group, suggested that psychoeducation could increase knowledge about symptoms, generate awareness of relevant services and enhance coping.; Conclusions: Psychoeducation may be an important foundational ingredient of interventions for perinatal depression and, potentially, anxiety in adolescents and young adults through stimulating help-seeking and self-care.

Mi, Z., et al. (2021). "Clinical efficacy and nursing experience of targeted nursing intervention combined with clotrimazole vaginal tablets in pregnant patients with candidal vaginitis." Basic & clinical pharmacology & toxicology 128(SUPPL 3): 36.
	Objective: The purpose was to explore the clinical effect of targeted nursing intervention combined with clotrimazole vaginal tablets in pregnant patients with candidal vaginitis. Methods: 120 pregnant patients with candidal vaginitis admitted to our hospital from January 2019 to January 2020 were selected, and randomly divided into group A (n = 60) and group B (n = 60). The group A received targeted nursing intervention combined with clotrimazole vaginal tablets while the group B received routine nursing combined with clotrimazole vaginal tablets to compare the therapeutic effect and nursing effect between the two groups. Results: The total effective rate and nursing satisfaction rate in group A were significantly higher than those in group B (P < 0.05). The symptom score in group A after treatment was significantly lower than that in group B (P < 0.05). The number of patients with adverse symptoms in group A after treatment was significantly lower than that in group B (P < 0.05). Conclusion: Targeted nursing intervention combined with clotrimazole vaginal tablets can effectively improve the clinical symptoms of pregnant patients with candidal vaginitis and optimize the overall curative effect, which should be further popularized and applied in clinical practice.

Miao, C., et al. (2021). "Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis." The Journal of International Medical Research 49(7): 3000605211031758.
	OBJECTIVE: This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). METHODS: A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. RESULTS: A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = -0.37; 95% confidence interval -0.69, -0.05) and serum insulin (standardized mean difference = -0.66; 95% confidence interval -1.19, -0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. CONCLUSIONS: Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.

Miao, K. and H. Zhou (2022). "Effect of statins combined or not combined with metformin on polycystic ovary syndrome: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 48(7): 1806-1815.
	Background: This meta-analysis was conducted to evaluate the effect of statins combined or not combined with metformin on polycystic ovary syndrome (PCOS).; Methods: Databases were systematically searched from inception to February 2022. Meta-analysis was conducted by using STATA 12.0 software. In the study, standard mean difference (SMD) and 95% confidence intervals (CI) were computed as the effect size. A random effect model was used.; Results: Meta-analysis showed significant decline of total testosterone, free testosterone, dehydroepiandrosterone sulphate, androstenedione, luteinizing hormone (LH), LH to follicle-stimulating hormone (FSH) ratio, and prolactin in statin group. Our study also demonstrated significant decline of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in statin group. Moreover, we found significant decline of fasting glucose, insulin sensitivity index, and high-sensitivity C-reactive protein.; Conclusion: The meta-analysis showed that statin therapy was good for women with PCOS, and could improve clinical signs of PCOS. (© 2022 Japan Society of Obstetrics and Gynecology.)

miao, S., et al. (2022). "Efficacy of different interventions of Chinese medicine and Western medicine on serum inflammatory factors in patients with polycystic ovary syndrome: a systematic review and network meta-analysis."
	Review question Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women of childbearing age. The role of chronic low-grade inflammation in the development of PCOS has become a research focus in recent years. Therefore, there have been studies on the effects of different drug interventions on chronic low-grade inflammation in PCOS. Based on existing different drug interventions, including traditional Chinese medicine and Western medicine, this study conducted a network meta-analysis on the intervention effect of inflammatory markers in patients with PCOS, and conducted an overall evaluation of CRP by analyzing the effectiveness of the final end indicators IL-6, IL-8, TNF-α and hs -. To provide more accurate evidence-based basis for clinical drug use, so as to select more scientific, accurate and effective clinical intervention measures Searches From the completion of the database to October 21, 2022, two independent reviewers conducted systematic searches on the following databases: PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, we targeted the studies on the effect of traditional Chinese medicine or Western medicine intervention on inflammation in patients with PCOS, and only included randomized controlled trials（RCTs） on human studies. There were no restrictions on the date of publication of the study and the ethnic region and age of the participants included in the study Types of study to be included We included only randomized controlled studies (RCTs) with reports in Chinese and English that met the criteria for inclusion in this study. The intervention group was a drug intervention and the control group was a conventional western drug or placebo, and the outcome measures contained IL-6, IL-8, TNF ‐ alpha, and hs-CRP. Non-rct reviews, animal experiments, expert reports, and descriptive studies including cross-sectional studies, case reports, case series, ecological studies and analytical studies including case-control studies and cohort studies were excluded. Condition or domain being studied Polycystic ovary syndrome (Pcystic ovary syndrome) is the most common endocrine disease in women of childbearing age, with a prevalence rate of 4%-20%. The number of women affected by this disease accounts for 10%-13%. Clinically, it is mainly characterized by excessive androgen, polycystic ovary shape and ovulation dysfunction, which greatly affects the endocrine system and reproductive function of women. At the same time, due to the chronic, persistent and long treatment period of this disease, the treatment cost is not small. In terms of pcos treatment, we can treat the different symptoms of different phenotypes of pcos in the traditional sense. Internal inflammatory targets should also be explored, but at present, there is no research to summarize these effective drug intervention methods and analyze which drugs are more effective. Therefore, the statistical method of reticular meta-analysis was used in this paper to explore which drug interventions were more effective in improving the inflammatory state of pcos patients, in order to provide better clinical treatment plans Participants/population We mainly included women aged 18-49 years who met the Rotterdam criteria for diagnosis of PCOS, the diagnostic criteria for TCM syndrome differentiation and the Chinese guidelines for diagnosis and treatment of PCOS, without regional or ethnic restrictions. The subjects had not taken any drugs that affected the body's hormone (endocrine metabolism) and organ function for at least 3 months before the study. Patients with other diseases such as hyperprolactinemia, thyroid dysfunction, premature ovarian failure, congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome, hyperandrogenemia caused by androgen-secreting adrenal, pituitary and hypothalamic dysfunction, diabetes mellitus, cardiovascular disease, hypertension and other diseases mimicking the clinical features of pcos were excluded. Intervention(s), exposure(s) In accordance with the clinical practice guidelines established by the American Endocrine Society, we will include studies of subpharmacological interventions that primarily improve the endocrine and metabolic status of pcos, including: Chromium supplements, simvastatin, resveratrol, cardamom, selenium, soy isoflavones, metformin, zinc, Probiotic selenium supplements, inositol, folate, Vitamin D plus omega-3, atorvastatin, carnitine, melatonin, magnesium, Rimonabant, Vitamin D plus probiotics, pioglitazone, green tea capsules, MK-7 plus calcium supplements, omega-3, magnesium Added vitamin E, curcumin, coenzyme Q10, atorvastatin, simvastatin, berberine, low molecular weight heparin calcium combined with letrozole, added Huanglian Wentan Decoction, Huanglian Wentan Decoction combined with shaofu Zhuyu decoction, Tonifying kidney and invigorating spleen prescription. No additional non-drug interventions, and studies that have an impact on endocrine function. The included population conforms to the above inclusion criteria for this study. We excluded intervention studies without IL-6, IL-8, TNF ‐ alpha, and hs-CRP as outcome markers. Comparator(s)/control In accordance with clinical practice guidelines established by the American Endocrine Association, we included control interventions that included conventional medication (birth control pills, metformin) and placebo. Excluding additional additional non-drug interventions and studies that had an impact on endocrine function. The included population of the control group was consistent with that of the intervention group, that is, the included population criteria of our study were met. Main outcome(s) After the normality test, if p< 0.05 was consistent with the normal distribution. The primary outcomes were standard circulating inflammatory cytokines IL-6, IL-8, TNF ‐ alpha (whose concentrations were measured by ELISA ELISA kit), hs-CRP (whose concentrations were measured by immunoturbidimetric assay or ELISA kit). Blood samples were collected from patients in the fasting state. This study intended to apply the random effects model for STATA mesh meta-analysis after the initial data collection, and adopt the mean and standard deviation as statistics for effect analysis Additional outcome(s) None Data extraction (selection and coding) Two independent reviewers will evaluate and screen the included studies respectively. If there is any objection, a third reviewer will conduct the review, and the final decision will be made by the three reviewers after communication and discussion. After screening, the data in the study were extracted and sorted through Excel tables, which mainly included the characteristic information of the included population, the publication year of the article, the author, the type of study, the intervention methods of the control group and the intervention group, the statistical methods, the applied effect size, and the outcome indicators. Risk of bias (quality) assessment The quality of our included studies will be assessed by two independent reviewers for the potential risk of bias in included RCTS using the Cochrane Collaboration's systematic review tool. Strategy for data synthesis We first verified the methodological and statistical heterogeneity, and our outcome indicators were continuous variables. The I² test was used for homogeneity test. If the results were consistent with normal distribution, the random effects model was used for meta-analysis by STATA14.0; if not, the heterogeneity was analyzed by subgroup analysis and meta regression. The evidence networks for the effects of different interventions on these four outcome indicators were plotted, followed by mesh meta-analysis for the response rates of IL-6, IL-8, TNF ‐ alpha and hs-CRP of different interventions. The statistical effect sizes were expressed as mean ± standard deviation. Then, the cumulative probability ranking plots of the effective rate of area under the cumulative Ranking curve (SUCRA) were drawn respectively to evaluate the best treatment methods. Analysis of subgroups or subsets If heterogeneity exists, we will analyze the source of heterogeneity through subgroup analysis. Subgroup analysis may be performed, but it is difficult to specify groups in advance. According to the content included in the article, we can conduct subgroup analysis according to different categories Contact details for further information shi Zhang zs62245007@163.com Organisational affiliation of the review Heilongjiang University of Chinese medicine Review team members and their organisational affiliations [1 change] Professor miao Sun. Second Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine Miss shi Zhang. Heilongjiang University of Chinese medicine Professor Xin Mao. Heilongjiang Provincial Infectious Disease Prevention and Control Institute Professor Fang Xu. Second Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine Dr Fangyun Gu. 1）Department of Gynecology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen 518000, Guangdong, China. 2）Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China. Professor Xiaoling Feng. Second Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine Professor Lihui Hou. Second Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine Type and method of review Intervention, Network meta-analysis, Systematic review Anticipated or actual start date [1 change] 25 July 2023 Anticipated completion date [2 changes] 29 February 2024 Funding sources/sponsors [1 change] Supported by the National Natural Science Foundation of China (grant number 82174195), the National Natural Science Foundation of China (grant number 81804138), the National Natural Science Foundation of China (grant number 82004401), and the administration of Traditional Chinese Medicine of Heilongjiang Province (grant number ZHY2020-101). Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Medicine, Chinese Traditional; Network Meta-Analysis; Polycystic Ovary Syndrome Date of registration in PROSPERO 23 November 2022 Date of first submission 13 November 2022

Michaan, N., et al. (2021). "Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis." Reproductive Biology and Endocrinology 19(1): 153.
	Background: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Method(s): Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. Result(s): IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Conclusion(s): IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.Copyright © 2021, The Author(s).

Michele, P. and B. Giovanni (2022). "Botulinum toxin injection in vulva and vagina. Evidence from a literature Systematic Review."
	
Michener Chad, M., et al. (2023). "Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3." Gynecologic Oncology 178: 102-109.
	Objective: To evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus (HPV)-associated Vulvar intraepithelial neoplasia (VIN) 2/3.; Methods: Participants were enrolled on a prospective, IRB-approved, dose-escalation phase I trial testing either 1, 2 or 3 treatment cycles (5 days), every other week, as applicable. Clinical assessments were completed prior to each dose cycle and included exam and review of adverse event (AE) diary cards. HPV testing and colposcopy was completed at 15 and 28 weeks. AEs were assessed according to CTCAE 4.0 criteria. Complete responders (CR) underwent biopsy of the treated site at the 28-weeks while partial (PR) and non (NR)-responders underwent surgical resection or biopsy and ablation.; Results: Fifteen patients consented to and began treatment. Per-protocol assessments were completed in 100% at 15- and 80% at 28-weeks. All patients completed prescribed cycles with no grade 3 or 4 AEs. Vulvovaginal burning/ was the most common AE occurring in 93.3%. AEs were grade 2 in 23.7% and included vulvovaginal pruritus (n = 3), swelling (n = 3) and candidiasis (n = 2). The highest ORR was in the 3-cycle group (88.9% with 55.6% CR). HPV-16 was detected either alone (46.7%) or with other subtypes (33.3%) in 80% of lesions and 5 of 8 (62.5%) with CR had complete viral clearance.; Conclusions: Topical artesunate for treatment of high-grade VIN shows high tolerability, low toxicity and evidence for clinical response in this initial small series. The safety and observed responses support further study in a Phase II trial.; Competing Interests: Declaration of Competing Interest MP is employed by Frantz Medical Group, JLB has advised and run investigator-initiated clinical trials for multiple biotech companies including many that are involved in HPV related science. Specifically in regards to this study Dr. Belinson serves as a medical advisor to Frantz Viral Therapeutics. Outside of the presented work, CMM has recent/ current stock options/ ownership of MedaSync. All other authors have no conflicts of interest to disclose. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Michener, C. M., et al. (2021). "Meta-analysis of Laparoendoscopic Single-site and Vaginal Natural Orifice Transluminal Endoscopic Hysterectomy Compared with Multiport Hysterectomy: Real Benefits or Diminishing Returns?" Journal of Minimally Invasive Gynecology 28(3): 698-709.e691.
	Objective: Because minimally invasive hysterectomy has become increasingly performed by gynecologic surgeons, strategies to further improve outcomes have emerged, including innovations in surgical approach. We sought to evaluate the intraoperative and perioperative outcomes and success rates of laparoendoscopic single-site surgery (LESS) and vaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy in comparison with those of conventional multiport laparoscopic (MPL) hysterectomy. Data Sources: A librarian-led search of PubMed, Scopus, CINAHL, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was performed for case-control, retrospective cohort, and randomized controlled trials through May 2020. Methods of Study Selection: The inclusion criterion was publications comparing LESS or vNOTES hysterectomy with conventional MPL hysterectomy for the management of benign or malignant gynecologic disease. Four authors reviewed the abstracts and selected studies for full-text review. The manuscripts were reviewed, separately, by 2 authors for final inclusion and assessment of bias using either the risk-of-bias assessment tool or the Newcastle-Ottawa scale. Any disagreement was resolved by discussion with, or arbitration by, a third reviewer. The titles of 2259 articles were screened, and 108 articles were chosen for abstract screening. Full-text screening resulted in 29 studies eligible for inclusion. Tabulation, Integration, and Results: Extracted data were placed into REDCap (Vanderbilt University, Nashville, TN), and MPL hysterectomy was compared with single-port hysterectomy using meta-analysis models. The outcomes included estimated blood loss (EBL); operative (OP) time; transfusion; length of hospital stay (LOS); conversion to laparotomy; visual analog scale pain scores at 12 hours, 24 hours, and 48 hours; any complications; and 7 subcategories of complications. Random-effects models were built for continuous outcomes and binary outcomes, and the results are reported as standardized mean difference (SMD) or odds ratio (OR) and their corresponding 95% confidence intervals, respectively. Meta-analysis could not be performed for vNOTES vs MPL, given that only 3 studies met the eligibility criteria. When LESS and MPL were compared, there was a shorter OP time for MPL (SMD = -0.2577, p <.001) and lower rate of transfusion (OR = 0.1697, p <.001), without a significant difference in EBL (SMD = -0.0243, p =.689). There was a nonsignificant trend toward higher risk of conversion to laparotomy in the MPL group (OR = 2.5871, p =.078). Pain scores were no different 12 or 24 hours postoperatively but were significantly higher at 48 hours postoperatively (SMD = 0.1861, p =.035) in the MPL group. There were no differences in overall or individual complications between the LESS and MPL groups. In the vNOTES comparison, 2 studies demonstrated shorter OP times, with reduced LOS and no difference in complications. Conclusion(s): In this meta-analysis, we identified that LESS hysterectomy has comparable and low overall rates of complications and conversion to laparotomy compared with MPL. Notably, the OP time seems longer, and the pain scores at 48 hours may be lower with LESS hysterectomy than with MPL hysterectomy. Limited data suggest that vNOTES hysterectomy may have shorter OP times and improved EBL, transfusion rates, LOS, and pain scores compared with MPL hysterectomy, but further study is needed. There remains a deficit in high-quality data to understand the differences in cosmesis among these surgical approaches. The quality of data for this analysis seems to be low to moderate.Copyright © 2020 AAGL

Michigan University, o. and M. Health National Institute of (2021). A Wearable Morning Light Treatment for Postpartum Depression.
	No Results Available Device: Bright Light Therapy|Device: Dim Light Therapy Change in score for the Structured interview guide score for the Hamilton Depression Rating Scale - Seasonal Affective Version (SIGH-SAD total score)|Change in Phase angle difference|Edinburgh Postnatal Depression Scale (EPDS) total score|Epworth Sleepiness Scale (ESS) total score|Patient Reported Outcomes Measurement Information System (PROMIS) - Satisfaction with Participation in Social Roles (SPSR) total score|Patient Reported Outcomes Measurement Information System Sleep-related impairment (SRI) total score|Social functioning as measured by the Postpartum Bonding Questionnaire (PBQ) total score Female Not Applicable 120 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment HUM00190163|1R01MH121531-01A1 May 2025

Middelkoop, M.-A., et al. (2022). "Evaluation of marketing authorization and clinical implementation of ulipristal acetate for uterine fibroids." Human reproduction (Oxford, England) 37(5): 884-894.
	Ulipristal acetate (UPA) is a medical treatment for uterine fibroids and was authorized for surgical pre-treatment in 2012 after the conduct of the PEARL I and II randomized controlled trials and for intermittent treatment after the observational PEARL III and IV trials. However, UPA came into disrepute due to its temporary suspension in 2017 and 2020 because of an apparent association with liver injury. This clinical opinion paper aims to review the process of marketing authorization and implementation of UPA, in order to provide all involved stakeholders with recommendations for the introduction of future drugs. Before marketing authorization, the European Medicines Agency (EMA) states that Phase III registration trials should evaluate relevant outcomes in a representative population, while comparing to gold-standard treatment. This review shows that the representativeness of the study populations in all PEARL trials was limited, surgical outcomes were not evaluated and intermittent treatment was assessed without comparative groups. Implementation into clinical practice was extensive, with 900 000 prescribed treatment cycles in 5 years in Europe and Canada combined. Extremely high costs are involved in developing and evaluating pre-marketing studies in new drugs, influencing trial design and relevance of chosen outcomes, thereby impeding clinical applicability. It is vitally important that the marketing implementation after authorization is regulated in such way that necessary evidence is generated before widespread prescription of a new drug. All stakeholders, from pharmaceutical companies to authorizing bodies, governmental funding bodies and medical professionals should be aware of their role and take responsibility for their part in this process. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Middelkoop, M.-A., et al. (2021). "Uterine artery embolization versus surgical treatment in patients with symptomatic uterine fibroids: Protocol for a systematic review and meta-analysis of individual participant data." European Journal of Obstetrics, Gynecology, and Reproductive Biology 256: 179-183.
	Objective: Uterine fibroids are the most common benign tumours in women of the reproductive age. Symptoms of heavy menstrual bleeding, abdominal discomfort and infertility may seriously affect a woman's quality of life. Uterine artery embolization is a safe and effective alternative treatment to hysterectomy or myomectomy for symptomatic uterine fibroids. Which treatment provides the highest quality of life, least complications, symptom reduction and least chance intervention, has not been established and might depend on strict patient selection. This study aims to identify which specific subgroups benefit most of each treatment by analyzing individual participant data derived from randomized controlled trials of women undergoing embolization or surgical treatment. This study will primarily assess the effectiveness of both treatment groups by evaluating the effect on quality of life of embolization in comparison to surgery on specific patient and fibroid characteristics and the possible need for re-intervention for fibroid-related symptoms.; Data Sources: PubMed/MEDLINE, Embase and The Cochrane Library were searched up to August 2020.; Study Eligibility Criteria: We will collect individual participant data from randomized controlled trials that studied clinical and procedural outcomes of premenopausal women with symptomatic uterine fibroids, who were randomized between uterine artery embolization and surgery.; Study Appraisal and Synthesis Methods: Individual participant data from all eligible trials will be sought and analysed according to intention-to-treat principle. Risk of Bias will be done by using version 2 of the Cochrane tool for Risk of Bias in randomized trials. Subgroup analyses to explore the effect of e.g. age, fibroid characteristics and fibroid complaints will be performed, if data is available. This individual patient data meta-analysis will be analysed according to a one-stage model.; Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare. (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Middelkoop, M.-A., et al. (2021). "A multi-centre, randomized, non-inferiority trial to compare ulipristal with standard surgical treatment in women with symptomatic uterine fibroids: Protocol of the MYOMEX-2 trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 256: 63-69.
	Objectives: Fibroids are the most common benign tumours found in the uterus and can cause various symptoms. In 20-50 % of the women, an intervention is required. When conservative options fail, invasive options such as hysterectomy, uterine artery embolization or myomectomy are eligible options. Ulipristal acetate (UPA) was launched as the sole available long term pharmaceutical treatment, with the potential to avoid surgery. It is suggested that UPA improves quality of life, reduces symptoms and fibroid volumes. However, UPA is an expensive medicine, is possibly associated with liver injury and has never been directly compared to surgical treatment. The aim of this trial is to compare UPA to surgical treatment on both effectiveness and cost-effectiveness. Primary outcome is the reduction in symptom severity scores (part of the Uterine Fibroid Symptom and Quality of Life questionnaire) at 24 months of follow-up compared to baseline. Secondary outcomes include quality of life, societal costs, societal participation, liver function variation, patient satisfaction and preference. Outcomes will be analysed according to intention-to-treat principle.; Study Design: The MYOMEX-2 trial is an open-label, multicentre, non-inferiority randomized controlled trial. Patients are pre-menopausal women with symptomatic fibroids eligible for surgical treatment (hysterectomy, myomectomy or UAE). Fibroid symptoms may comprise (but are not limited to) heavy menstrual bleeding, bulk symptoms or pain. Patients are randomised 2:1 in a parallel group design between two treatment arms: 119 patients in the UPA group and 60 patients in the surgery group. Follow up comprises of online questionnaires, outpatient visits and phone appointments on several follow up moments, up to 24 months after surgery or start UPA.; Registration Details: MYOMEX-2 trial; protocol version 4, date 22-02-2019; NTR6860; NL62638.029.18. All items from the World Health Organization Trial Registration Data Set are provided in the online supplementary file (Appendix-B).; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Miedziaszczyk, M., et al. (2023). "Effects of Isoflavonoid and Vitamin D Synergism on Bone Mineral Density-A Systematic and Critical Review." Nutrients 15(24): 5014.
	Phytoestrogens are non-steroidal plant compounds, which bind to alpha and beta estrogen receptors, thereby causing specific effects. The best-known group of phytoestrogens are flavonoids, including isoflavonoids-genistein and daidzein. They play a role in the metabolism of bone tissue, improving its density and preventing bone loss, which contributes to reducing the risk of fractures. Vitamin D is found in the form of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) and is traditionally recognized as a regulator of bone metabolism. The aim of this review was to evaluate the synergistic effect of isoflavonoids and vitamin D on bone mineral density (BMD). The MEDLINE (PubMed), Scopus and Cochrane databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. Reference publications did not provide consistent data regarding the synergistic effect of isoflavonoids on BMD. Some studies demonstrated a positive synergistic effect of these compounds, whereas in others, the authors did not observe any significant differences. Therefore, further research on the synergism of isoflavonoids and vitamin D may contribute to a significant progress in the prevention and treatment of osteoporosis.Copyright © 2023 by the authors.

Miele, G. M., et al. (2021). "A New Combined Laparoscopic-Vaginal Lateral Suspension Procedure for the Treatment of Pelvic Organ Prolapse." Urology 149: 263.
	OBJECTIVE: To show an original technique of a new combined vaginal-laparoscopic lateral suspension in Hysteropexy with cistocele and rectocele. In recent years, changes in attitudes toward sexuality, psychological value of reproductive organs and the desire to preserve fertility have led to a growing interest in uterine-preserving surgery for Pelvic Organ prolapse. Minimally invasive procedures derived from sacrocolpopexy are considered the gold standard in the treatment of apical Pelvic Organ prolapse. However, dissection at the level of the promontory may be challenging, particularly in obese women and when an anatomical variation exists. This may be associated with rare but serious neurological or ureteral morbidity as well as life-threatening vascular injury. MATERIALS AND METHODS: Stepwise demonstration of the technique with narrated video footage. Local institutional review board was consulted, and this study was exempted from approval. RESULTS: Our technique entails 2 times. During the vaginal time, a polypropylene mesh is fixed to the cervical fascia and the 2 extremities are introduced in the abdominal cavity through the Douglas pouch. During the laparoscopic time, a retroperitoneal tunnel is made along the walls of the lateral abdominal walls; thereafter, each of the 2 extremities of the mesh is passed through the omolateral tunnel and "tension-free" suspended to the abdominal wall. CONCLUSION: Our combined technique may allow a safer approach, reducing the risks of serious complications. Moreover, it leads to a more physiological orientation of the vaginal axis. Further controlled studies are needed to confirm our suggestion.

Miglani, U., et al. (2022). "EVALUATION OF CERVICAL CYTOLOGY IN WOMEN ON TAMOXIFEN THERAPY." International Journal of Gynecological Cancer 32(Supplement 2): A387.
	Introduction/Background Tamoxifen, a selective estrogenic receptor modulator, is used for hormonal treatment of all stages of hormone receptor positive breast cancer due to its anti-estrogenic effect on breast tissues. Estrogen receptors are also present in squamous and columnar epithelium of cervix and vagina and are responsible for the changes in cervico-vaginal epithelium.In view of the potential adverse effects of tamoxifen on cervical cytology, this study was planned to study those effects on cervical cytology. Methodology This is a cross sectional study done in Deen Dayal Upadhyay Hospital on the patients of breast cancer taking tamoxifen therapy. Patients of breast cancer on tamoxifen therapy for more than 6 months and currently on tamoxifen are included. The results are compared with Papanicolaou smear of healthy adult females coming for screening in cancer screening OPD without any gynaecological problem. Data is coded and recorded in MS Excel spreadsheet program. SPSS v23 (IBM Corp.) is used for data analysis. Group comparisons for continuously distributed data is made using independent sample 't' test when comparing two groups. Chi-squared test is used for group comparisons for categorical data. Results 50 patients of breast cancer on tamoxifen therapy were taken as cases and 50 healthy women were included as controls.Mean age for the cases and controls was 48.5 years and 46.88 years respectively. Mean parity for cases and controls was 3.84 and 3.48 respectively. There was no significant increase in the frequency of squamous or glandular abnormalities in the patients on Tamoxifen therapy. Conclusion There is no significant deleterious affect of Tamoxifen on cervical cytology. More research is required to confirm a protective effect.

Miglani, U., et al. (2022). "TO STUDY THE IMPACT OF IMPLEMENTATION OF ENHANCED RECOVERY AFTER SURGERY (ERAS) PROTOCOL ON PERIOPERATIVE OUTCOMES IN GYNECOLOGY ONCOLOGY SURGERY PATIENTS." International Journal of Gynecological Cancer 32(Supplement 2): A213-A214.
	Introduction/Background ERAS guideline 2019 outlines the most current recommendations of the ERAS Society Group for the perioperative management of patients undergoing gynaecologic/oncology surgery, and is based on the best available evidence. The primary clinical benefits of implementing these protocols are shorter hospital, length of stay and reduced post-operative complications (including respiratory complications) in low, medium and high complexity gynaecologic oncology surgeries. In view of the above facts, the present study is planned to study the influence of implementation of ERAS protocol on postoperative recovery and outcome in gynaecologic oncology patients. Methodology The study population comprises of all gynaecology oncology patients more than 18 years of age who undergo laparotomy with a provisional or proven diagnosis of cancer of the uterus, cervix or ovary. The patients were randomized in two groups by block randomization: Group EERAS protocol and Group C- Conventional protocol The following measures were taken for Group E patients: preoperative bathing.no preoperative sedative medication, preoperative antibiotic within 60 minutes of incision, no long-acting opioids, no drains or nasogastric tube, compression stockings postoperatively, low molecular weight heparin given postoperatively, use of chewing gum in postoperative phase, mobilization on day of surgery. The outcome measures include duration of hospital stay, readmission within 21 days, time taken for return of bowel function, rate of postoperative ileus and incidence of surgical site infections. Results 30 patients were included in Group E and Group C each. The duration of hospital stay, rate of postoperative ileus and incidence of surgical site infections were significantly decreased in the ERAS group. Conclusion ERAS protocol has a significant beneficial effect on perioperative outcomes in Gynaecologic oncology patients.

Miguel, M.-G., et al. (2023). "Use of electrophysical agents in adult women with chronic pelvic pain (CPP): A systematic review and meta-analysis."
	
Mihail, D., et al. (2021). "Hysteroscopic treatment of Cesarean Scar Pregnancy: A Systematic Review."
	
Mihaylov, I., et al. (2021). "Serous psammocarcinoma of the ovary: Case report with systematic review." Medical Studies/Studia Medyczne 37(3): 261-267.
	Psammocarcinoma is a rare subtype of serous epithelian neoplasms arising from the ovaries and the peritoneum. It is characterized by massive psammoma body formation, low-grade cytological features, and invasiveness. We present a case of a 59-year-old female diagnosed with relapse of ovarian psammocarcinoma. She was operated 4 years previously and did not undergo chemotherapy. We performed a systematic search on this topic using the PubMed and ScienceDirect databases. In the literature 33 cases of ovarian psammocarcinoma are reported. We discuss the clinicopathological features of these patients. Ovarian psammocarcinoma is a rare and not well described disease. Due to the small number of cases found in the literature, no conclusions can be drawn about the tumour characteristics.Copyright © 2021 Termedia Publishing House Ltd.. All rights reserved.

Mikel, A., et al. (2021). "Effects of intra-uterine platelet-rich plasma (PRP) infusion in women with a history of failed embryo transfer."
	
Miklos, A. C. S., et al. (2022). "Hyperthermic Intraperitoneal Chemotherapy With Cisplatin and Doxorubicin for 90 Minutes Versus 60 Minutes After Cytoreductive Surgery (CRS). Does the 30-Minute Difference Matter? A Comparative Study in a High Volume Centre." Anticancer Research 42(2): 1019-1029.
	Background/Aim: This study compared the perioperative outcomes after the same combination of hyperthermic intraperitoneal chemotherapy (HIPEC) compounds when administered for 90 min vs. 60 min, while all other therapy variables remained constant. Patients and Methods: A total of 120 patients were included with peritoneal surface malignancy who underwent cisplatin (75 mg/m2) and doxorubicin (15 mg/m2) closed HIPEC after cytoreductive surgery. Result(s): Sixty-five patients (54.2%) in the 60 min and 55 patients (45.8%) in the 90 min HIPEC group were compared. Patients, tumor characteristics, and postoperative complications were comparable. The only significant difference was the rate of chest drain/pleural puncture with an incidence of 18.5% and 34.5% in the 60 min and 90 min group, respectively (p=0.045). After adjustment in a multivariable regression analysis, the odds for patients with HIPEC 90 min of having chest drain or pleural puncture in comparison to patients with HIPEC 60 min was still higher, but not significant with an OR of 2.238 (95%CI=0.932-5.373; p=0.071). Conclusion(s): HIPEC administered for 90 min is safe and does not increase perioperative morbidity and mortality compared to the 60-min administration.Copyright © 2022 International Institute of Anticancer Research. All rights reserved.

Miklós, D., et al. (2023). "[Laparoscopic treatment of deeply infiltrating colorectal endometriosis - ten years of single center experience]." Orvosi hetilap 164(9): 348-354.
	INTRODUCTION: Deep infiltrating endometriosis penetrates the peritoneal surface beneath 5 mm. The bowel is affected in 3-37% of the cases. OBJECTIVE: The aim of the authors was to analyze the results of the surgical procedures performed for bowel endometriosis. METHOD: Between 2009 and 2020, 675 patients underwent bowel endometriosis surgery at the Department of Obstetrics and Gyanecology of Semmelweis University. Four surgical approaches were performed: shaving, discoid, segmental and NOSE resection. RESULTS: 182 shaving, 93 discoid, 130 NOSE and 270 segmental bowel resections were performed. Ultra-deep anastomosis was performed in 40 cases. The median operative time was 85 minutes, the shortest intervention lasted 25 minutes, the longest 585 minutes. The average operating time was 260 (± 161.3) minutes for the first, and 114 (± 47.0) minutes for the last ten operations. The average blood loss was 10 (± 20.3) mL. The average hospital stay was 6 (± 2.3) days. Serious surgical complication (Clavien-Dindo III or more severe) developed in 18 cases. In a total of 17 cases sigmoideo- or ileostomy were used. Conversion to laparotomy was necessary in 6 cases. DISCUSSION: The same team performed all the interventions, which can show the effectiveness of the surgical techniques instead of the technique of individual surgeons. The complication rate is low in the case of an experienced surgical team, and the operating time decreases significantly in proportion to the number of operations performed. CONCLUSION: Bowel endometriosis can be treated safely and effectively with both conservative (shaving or discoid) and radical (segmental or NOSE resection) approach. Orv Hetil. 2023; 164(9): 348-354.

Mikocka-Walus, A., et al. (2021). "Yoga, cognitive-behavioural therapy versus education to improve quality of life and reduce healthcare costs in people with endometriosis: a randomised controlled trial." BMJ Open 11(8): e046603.
	Introduction: Endometriosis is a debilitating chronic inflammatory condition highly burdensome to the healthcare system. The present trial will establish the efficacy of (1) yoga and (2) cognitive-behavioural therapy (CBT), above (3) education, on quality of life, biopsychosocial outcomes and cost-effectiveness.; Methods and Analysis: This study is a parallel randomised controlled trial. Participants will be randomly allocated to yoga, CBT or education. Participants will be English-speaking adults, have a diagnosis of endometriosis by a qualified physician, with pain for at least 6 months, and access to internet. Participants will attend 8 weekly group CBT sessions of 120 min; or 8 weekly group yoga sessions of 60 min; or receive weekly educational handouts on endometriosis. The primary outcome measure is quality of life. The analysis will include mixed-effects analysis of variance and linear models, cost-utility analysis from a societal and health system perspective and qualitative thematic analysis.; Ethics and Dissemination: Enrolment in the study is voluntary and participants can withdraw at any time. Participants will be given the option to discuss the study with their next of kin/treating physician. Findings will be disseminated via publications, conferences and briefs to professional organisations. The University's media team will also be used to further disseminate via lay person articles and media releases.; Trial Registration Number: ACTRN12620000756921p; Pre-results.; Competing Interests: Competing interests: AM-W has served as an educational speaker for Janssen and Ferring. SK has served as an educational speaker for Janssen, Ferring and Takeda. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mikos, T., et al. (2020). "The Outcome of Fertility-Sparing and Nonfertility-Sparing Surgery for the Treatment of Adenomyosis. A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 27(2): 309.
	Objective: The purpose of this systematic review was to identify the operative issues and specific dysmenorrhea and menorrhagia outcomes in women who had undergone fertility-sparing surgery, as well as determine the expected outcome for extirpative surgery.; Data Sources: PROSPERO (ID no. 125692). Search was conducted for eligible studies up to March 31, 2019, on MEDLINE/PubMed (1966-2019), Scopus/Elsevier (1950-2019), and Google Scholar (up to 2019). The search terms applied for the search strategy were as follows: adenomyosis, adenomyomas, uterus-sparing surgery, fertility-sparing surgery, pain, dysmenorrhea, menorrhagia, uterine volume, adenomyotic volume, case-control studies, cohort studies, and prospective studies.; Methods of Study Selection: A total of 443 studies were initially identified. Exclusion criteria was as follows: (1) inadequate description of preoperative adenomyosis or absence of postoperative histology confirmation of adenomyosis, (2) no statement of use of a standardized instrument for measurement of pain, bleeding, or adenomyotic/uterine volume, (3) follow-up <12 months postoperatively, (4) study population <20 women, and (5) non-English language.; Tabulation, Integration, and Results: Nineteen studies with a total of 1843 patients with adenomyosis were included. Twelve studies were further analyzed in the meta-analysis. Complete excision of adenomyosis was associated with improvement in pain, menorrhagia, and reduction of uterine volume by a factor of 6.2, 3.9, and 2.3, respectively; the partial excision of adenomyosis was associated with improvement in pain, menorrhagia, and reduction of uterine volume by a factor of 5.9, 3.0, and 2.9, respectively; the studies with a mixed volume of patients with complete and partial excision of adenomyosis reported improvement in pain, menorrhagia, and reduction of uterine volume by a factor of 4.0, 6.3, and 5.1, respectively.; Conclusion: The surgical treatment of adenomyosis results in the satisfactory control of pain and bleeding, as well as in the reduction of uterine volume. Further research is warranted to investigate the long-term control of symptoms to identify any parameters related to the recurrence of adenomyosis, as well as to compare the conservative surgical treatment of adenomyosis with other treatment options. (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Mikus, M., et al. (2021). "Comparison of efficacy of extracorporeal magnetic innervation and Kegel exercises for stress urinary incontinence in adult women: Study protocol for a randomized controlled trial." Przeglad Menopauzalny 20(4): 193-200.
	Stress urinary incontinence (SUI) is defined as a complaint of inadvertent loss of urine occurring as a result of an increase in intraabdominal pressure. Strong evidence supports the use of pelvic floor muscle training (PFMT) as the first-line conservative treatment for SUI. Extracorporeal magnetic stimulation (EMS) is a noninvasive, effective, acceptable, and safe therapeutic modality for SUI. Although PFMT and EMS share most of their influences on the pathophysiology of SUI, it is unclear whether one of these routinely used treatment modalities is superior to another in terms of improvement of clinical outcomes or cost-effectiveness. To the best of our knowledge, no randomized controlled trials have so far directly compared PFMT with EMS. Our aim here is to describe a protocol for such a study. This will be a parallel-group, single-blind, randomised controlled trial compliant with the SPIRIT, CONSORT, and TIDieR reporting guidelines. Participants will be women aged 18 to 65 years who have previously given at least one vaginal delivery (at least 12 months before joining the study) who present with symptoms of SUI lasting at least 6 months yet have not previously received treatment for it. In the first study arm, patients will receive an eight-week, high-intensity, home-based Kegel exercises regimen. In the second study arm, the treatment scheme will consist of 2 sessions of EMS per week for a total of eight weeks. The primary outcome will be effectiveness of treatment as measured by the International Consultation on Incontinence Questionnaire Urinary Incontinence- Short Form overall score, eight weeks, three months, and six months after commencement of treatment.Copyright © 2021 Termedia Publishing House Ltd.. All rights reserved.

Mikus, M., et al. (2022). "Efficacy Comparison between Kegel Exercises and Extracorporeal Magnetic Innervation in Treatment of Female Stress Urinary Incontinence: A Randomized Clinical Trial." Medicina (Kaunas, Lithuania) 58(12).
	Background and Objectives: To estimate the effectiveness of Kegel exercises versus extracorporeal magnetic innervation (EMI) in the treatment of stress urinary incontinence (SUI). Material(s) and Method(s): A parallel group, randomized clinical trial was conducted in the Department of Obstetrics and Gynecology, Clinical Hospital Centre Zagreb, Croatia. After assessing the inclusion/exclusion criteria, each eligible participant was randomized to one of the two observed groups by flipping a coin: the first group underwent treatment with Kegel exercises for 8 weeks, while the second group underwent EMI during the same time interval. The primary outcome was the effectiveness of treatment as measured by the ICIQ-UI-SF overall score, eight weeks after the commencement of treatment. Result(s): During the study period, 117 consecutive patients with SUI symptoms were assessed for eligibility. A total of 94 women constituted the study population, randomized into two groups: Group Kegel (N = 48) and Group EMI (N = 46). After 8 weeks of follow-up, intravaginal pressure values in the EMI group were 30.45 cmH2O vs. the Kegel group, whose values were 23.50 cmH2O (p = 0.001). After 3 months of follow-up, the difference was still observed between the groups (p = 0.001). After the end of treatment and 3 months of follow-up, the values of the ICIQ-UI SF and ICIQ-LUTSqol questionnaires in the EMI group were lower than in the Kegel group (p < 0.001). Treatment satisfaction was overall better in the EMI group than in the Kegel group (p < 0.001). Conclusion(s): Patients treated with EMI had a lower number of incontinence episodes, a better quality of life, and higher overall satisfaction with treatment than patients who performed Kegel exercises.

Mikus, M., et al. (2022). "Digital Therapeutic Device for Urinary Incontinence: a Randomized Controlled Trial." Obstetrics and Gynecology 140(1): 136.
	
Mikuš, M., et al. (2022). "State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(11): 911-917.
	Objective: The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain. Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 179 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, seven primary articles met the inclusion criteria. A systematic review of the data was conducted. Results: This review included several, non-hormonal emerging drug therapies for endometriosis-associated pelvic pain. Based on our results, we divided well-founded studies into three subgroups: antiangiogenic agents, immunomodulators, and natural components. Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors. Conclusion: Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration.

Mikus, M., et al. (2023). "Stress urinary incontinence and conservative treatment modalities: what is the effect on sexual function?" Maturitas 173: 88-89.
	Stress urinary incontinence (SUI) is a serious health problem in modern society. It significantly limits or even impairs the functioning of many areas of women's lives, including their sexual health. The aim of our prospective clinical study was to determine the impact of the two most commonly used conservative treatments (Kegel exercise and extracorporeal magnetic innervation - EMI) on a specific area of quality of life - sexual health. ICIQ-FLUTsex was the questionnaire used to assess sexual health before and after the assigned intervention was done. Between-group comparisons of ICIQ-FLUTsex questionnaire scores were analyzed by the Mann-Whitney U test. Within-group analysis of ICIQ-FLUTsex scores at different time intervals was undertaken using Friedman's ANOVA by ranks with Dunn-Bonferroni post-hoc tests. Statistical significance was set at p value < 0.05. The statistical analysis was conducted using IBM SPSS Statistics (Version 25.0). The total study population was randomized into two groups: Group Kegel (N=48) and Group EMI (N=46). In the first study arm, the patients received an 8-week, high-intensity, home-based Kegel exercise program. Patients in the EMI group have received treatment regimen consisted of 2 sessions per week for a total of 8 weeks. Each session lasted 30 min and consisted of a 15-min low-frequency stimulation program (10 Hz) followed by 15 min of a high-frequency stimulation program (50 Hz). Both groups were followed-up during 3 months. There was no significant difference in the main sociodemographic characteristics and menopausal status between the groups. Overall, our results show that women who suffered from SUI and were prescribed with conservative treatment modalities reported better sexual functioning during study period. However, patients who underwent EMI reported significantly better sexual functioning at 8 weeks (p=0.004) and 3 months (p=0.006) follow-up periods, in comparison to patients who were prescribed Kegel exercises. Moreover, within-group analyses showed significant differences in sexual functioning between different study periods in the EMI group (Q=57.435, p<0.001), which was confirmed by posthoc testing. There were no significant mean score differences between the 2nd and 3rd measurements of the ICIQ-FLUTSsex questionnaire in women with Kegel exercises. The results of our study show that sexual function improves even after a short treatment with EMI and Kegel exercises, but continuous treatment is essential.Copyright © 2023

Milagros, M., et al. (2022). "Quality of life for women with primary dysmenorrhea that are making therapeutic exercises programs: a systematic review."
	
Mileshkin, L. R., et al. (2021). "Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: the randomized phase III OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274)." Journal of Clinical Oncology 39(18 SUPPL).
	Background: Cervical cancer is a common cause of cancer‐related death among women worldwide. Standard treatment for locally advanced disease is chemoradiation. However, a significant percentage of women still relapse and die from the development of distant metastatic disease. OUTBACK was designed to determine the effects of giving adjuvant chemotherapy after chemoradiation on survival. Methods: OUTBACK is an international randomized phase III trial of the Gynecologic Cancer InterGroup (GCIG). Participating groups (countries) included ANZGOG (Australia and New Zealand), NRG (USA, Saudi Arabia, Canada, China), and Singapore. Eligible women had locally advanced cervical cancer (FIGO 2008 stage IB and node positive, IB , II, IIIB or IVA) that was suitable for primary treatment with chemo‐radiation with curative intent. Women were randomly assigned to either standard cisplatin‐based chemo‐radiation (control) or standard cisplatin‐based chemo‐radiation followed by adjuvant chemotherapy (ACT) with 4 cycles of carboplatin and paclitaxel, after stratification for nodal status, participating site, FIGO stage, age, and planned extended‐field radiotherapy. The primary end point was overall survival (OS) at 5 years. Secondary endpoints included progressionfree survival (PFS); adverse events (AE); and patterns of disease recurrence. The target sample size of 900 provided 80% power with 95% confidence to detect an improvement in OS at 5 years from 72% (control) to 80% (ACT), with some over‐accrual to account for non‐compliance with ACT and loss to follow‐up. Results: 919 of 926 women recruited from April 2011 to June 2017 were eligible and included in the primary analysis: 463 assigned ACT, 456 control. ACT was started in 361 (78%) women assigned to receive it. Median follow‐up was 60 months (IQR 45‐65). OS at 5 years was similar in those assigned ACT versus control (72% vs 71%, difference <1%, 95% CI ‐6 to +7; P = 0.91). The hazard ratio for OS was 0 91, (95% CI 0.70 to 1.18). PFS at 5 years was similar in those assigned ACT versus control (63% vs 61%, difference 2%, 95% CI ‐5 to +9; P = 0.61). The hazard ratio for PFS was 0 87, (95% CI 0.70 to 1.08). AE of grade 3‐5 within a year of randomisation occurred in 81% who were assigned and received ACT versus 62% assigned control. There was no evidence of differences between treatment groups in AE beyond 1 year of randomisation. Patterns of disease recurrence were similar in the two treatment groups. Conclusions: Adjuvant chemotherapy given after standard cisplatin‐based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS.

Mileshkin, L. R., et al. (2022). "Staging locally advanced cervical cancer with FIGO 2018 versus FIGO 2008: Impact on overall survival and progression-free survival in the OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274)." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: The International Federation of Obstetrics and Gynecology staging system for cervical cancer (FIGO 2008) was revised in 2018 to incorporate lymph node involvement (FIGO 2018). OUTBACK is an international, randomized phase 3 trial of adjuvant chemotherapy versus observation after standard of care treatment with chemoradiation for women with locally advanced cervical cancer. OUTBACK found no benefit from the addition of adjuvant chemotherapy. We evaluated the effects of classifying participants with these 2 staging systems in the OUTBACK trial population. Method(s): OUTBACK recruited April 2011 to June 2017 and staged participants according to FIGO 2008. Lymph node status, smoking status, age, race and histological subtype were documented at trial entry as important prognostic factors. We assessed the effects of stage grouping into stage I, II, and III/IVa with FIGO 2008 versus FIGO 2018, on progression-free survival (PFS) and overall survival (OS) at 5 years using Kaplan-Meier estimates, and in univariable proportional-hazards regression analyses, and in multivariable analyses adjusting for important prognostic factors and randomly allocated treatment. Result(s): All 919 study participants had complete data for staging according to the 2 staging systems and most prognostic factors for adjustment. Among all participants, the 5-year outcomes were PFS = 62% and OS = 72%. Classification according to FIGO 2018 rather than FIGO 2008 yielded higher 5-year PFS and OS in each stage group (see table for numbers of participants, PFS and OS for each stage group). Predictors of PFS in multivariable analysis included squamous vs non-squamous histology (HR 0.71 for FIGO 2008 and 0.74 for FIGO 2018), but not nodal involvement when FIGO 2018 was used. Both staging systems were the only independently significant prognostic factors in both univariable and multivariable analyses (all p < 0.0001) for both PFS and OS. Conclusion(s): Compared to FIGO 2008, reclassifying pts by FIGO 2018 staging resulted in more pts being classified as stage 3 due to the incorporation of nodal status. Staging locally advanced cervical cancer using FIGO 2018 rather than FIGO 2008 resulted in higher PFS and OS in each stage grouping that reflected stage migration, not a true improvement in outcomes. FIGO stage remains the strongest predictor of overall survival after CRT but survival outcomes by stage in trials using the old vs new staging system are not comparable.

Millan, D. M., et al. (2023). "Optimization of the Mood Disorder Questionnaire in identification of perinatal bipolar disorder." American Journal of Obstetrics and Gynecology MFM 5(1): 100777.
	BACKGROUND: The recognition of bipolar disorder during the perinatal period is often challenging because birthing people most commonly present in a depressive episode. The phenotypic expression of episodes of bipolar depression is difficult to differentiate from major depressive disorder and can lead to misdiagnosis and inappropriate treatment. The Mood Disorder Questionnaire is a readily available screening tool for bipolar disorder that has been validated in previous studies for use in the general and perinatal populations. However, the discriminatory capacity of the Mood Disorder Questionnaire for perinatal people who screen positive for depression in nonpsychiatric settings is still unclear. OBJECTIVE(S): This study aimed to evaluate the discriminatory capacity of the Mood Disorder Questionnaire to identify bipolar disorder in perinatal people who screen positive for depression on the Patient Health Questionnaire-9. STUDY DESIGN: This retrospective cohort study included individuals enrolled in the Collaborative Care Model for Perinatal Depression Support Services, a collaborative care program for perinatal mental health services implemented in a quaternary care setting, from January 2017 to April 2021. All individuals completed the Mood Disorder Questionnaire and psychiatric evaluation by a licensed clinical social worker. Clinical and sociodemographic characteristics were compared between those with and without a clinical diagnosis of bipolar disorder using bivariable analyses. The discriminatory capacity and test characteristics of the Mood Disorder Questionnaire were assessed at each score cutoff using the gold standard of a psychiatric clinical evaluation for comparison. RESULT(S): From January 2017 to April 2021, 1510 birthing people were enrolled in the Collaborative Care Model for Perinatal Depression Support Services and included in this study. Among this group, 62 (4.1%) were diagnosed with bipolar disorder by psychiatric clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria. A score of >=7 on question 1 is often used in the general population to identify bipolar disorder, which has a 60% sensitivity and 88% specificity in our perinatal sample with an area under the receiver operating characteristic curve of 0.74 (95% confidence interval, 0.72-0.76). Lowering the threshold to >=4 improves sensitivity to 81% and the discriminatory capacity to an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.70-0.80), at the expense of a reduction in specificity to 69%. CONCLUSION(S): The administration of the Mood Disorder Questionnaire in the perinatal period can help to identify which individuals who have screened positive for depression on the Patient Health Questionnaire-9 are at risk of a bipolar or unipolar disorder. In this context, lowering the Mood Disorder Questionnaire score threshold from that used in the nonperinatal population down to 4 improves test characteristics and reduces the risk of a missed diagnosis of bipolar disorder.Copyright © 2022 Elsevier Inc.

Miller, D., et al. (2022). "Pregnancy outcomes related to the treatment of sarcomas with anthracyclines and/or ifosfamide during pregnancy." Cancer Medicine 11(18): 3471-3478.
	Background: Sarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy-associated sarcomas. Patients and Methods: We conducted a multi-institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank-sum test compared two independent samples. Result(s): We identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 +/- 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 +/- 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016). Conclusion(s): In this multi-institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study.Copyright © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Miller, D., et al. (2022). "PHASE 3 STUDY ASSESSING THE EFFICACY OF ADDING AL3818 (CATEQUENTINIB DIHYDROCHLORIDE, ANLOTINIB HYDROCHLORIDE) TO CHEMOTHERAPIES IN SUBJECTS WITH PLATIMUM RESISTANT AND REFRACTORY OVARIAN CARCINOMA." International Journal of Gynecological Cancer 32(Supplement 3): A240.
	Objectives AL 3818 is a novel, orally administered, small molecule tyrosine kinase inhibitor, that shows highly selective inhibition of fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR). The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 in combination with chemotherapy in patients with platinum resistant and refractory ovarian carcinoma. Methods The study is a phase 3, multi-center, randomized trial at 1:1 ratio with active control designed to evaluate the efficacy and safety of AL3818 plus background chemotherapy treatment (Active Arm) vs. background chemotherapy treatment alone (Control Arm), where one of three background treatments, weekly paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan is utilized. Patients with a diagnosis of platinum resistant or platinum refractory ovarian carcinoma requiring third line, or any further line treatment are eligible for enrollment. The regimen is a 21-day cycle with oral AL3818 at 8 mg administered on days 8-21, with days 1-7 off combining with one of the three chemotherapies in Active Arm. Maintenance monotherapy with AL3818 is an option if chemotherapy is discontinued. The primary objective of this study is to evaluate the efficacy between the Active Arm and Control Arm as measured by the primary endpoint of Progression Free Survival (PFS). The study is opening in US, UK, ES, IT and Asia. Clinical trial information: NCT02584478. Results There are no available results at the time of submission. Conclusions There are no available results at the time of submission.

Miller, E. S., et al. (2022). "Trajectories of antenatal depression and adverse pregnancy outcomes." American Journal of Obstetrics and Gynecology 226(1): 108.e101-108.e109.
	Background: Antenatal depression affects approximately 1 of 7 pregnancies, with an increasing prevalence across gestation. Data regarding the associations between antenatal depression and adverse pregnancy outcomes yielded conflicting results. However, previous studies evaluated the cross-sectional prevalence of depression at various time points and not the depressive symptom trajectory across gestation. Objective(s): This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes. Study Design: This was a secondary analysis of a large multisite prospective cohort of nulliparous women across the United States. The Edinburgh Postpartum Depression Scale was administered at 2 study visits: between 6 and 14 weeks' gestation and between 22 and 30 weeks' gestation. The Edinburgh Postpartum Depression Scale score trajectories were categorized as improved, stable, or worsened based on whether the scores changed by at least 1 standard deviation between the 2 visits. The frequencies of adverse pregnancy outcomes (hypertensive disorders of pregnancy, abruption, cesarean delivery, preterm birth [ie, <37 weeks' gestation], small for gestational age neonates, neonatal intensive care unit admission, and maternal readmission) were compared with depression trajectories across gestation in bivariable and multivariable analyses. Secondary analyses evaluated the frequencies of spontaneous and medically indicated preterm births and frequencies of spontaneous and medically indicated preterm births before 35, 32, and 28 weeks' gestation. Result(s): Of the 8784 women who completed the 2 antenatal Edinburgh Postpartum Depression Scale screens, 1141 (13.0%) had improved, 6663 (75.9%) had stable, and 980 (11.2%) had worsened depressive symptom trajectories across gestation. Compared with women with improved or stable depressive symptoms, those with worsened symptoms were more likely to experience preterm birth (8.3% vs 7.4% vs 9.9%, respectively; P=.018). After controlling for potential confounders, worsened depressive symptoms remained associated with more frequent preterm birth (adjusted odds ratio, 1.68; 95% confidence interval, 1.10-2.57). Conclusion(s): Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth.Copyright © 2021 Elsevier Inc.

Miller, K. N., et al. (2024). "GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder." Psychoneuroendocrinology 160: 106684.
	Rationale: Premenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD's pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD. Aim(s): The aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms. Method(s): Participants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3alpha,5alpha-THP; 3alpha5beta-THP; pregnenolone; 3alpha,5alpha-androsterone; 3alpha,5beta-androsterone; 3alpha,5alpha-A-diol; 3alpha5beta-A-diol; 3alpha,5alpha-THDOC; 3alpha5beta-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50 mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment. Result(s): Participants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (p > 0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3alpha,5alpha-androsterone. Conclusion(s): This was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design.Copyright © 2023 Elsevier Ltd

Miller Larry, E., et al. (2020). "Clinical Utility of Presacral Neurectomy as an Adjunct to Conservative Endometriosis Surgery: Systematic Review and Meta-Analysis of Controlled Studies." Scientific Reports 10(1): 6901.
	The objective of this review was to compare the efficacy and safety of conservative surgery with or without adjunctive presacral neurectomy (PN) for chronic endometriosis-related pelvic pain. In a systematic review with meta-analysis, randomized or nonrandomized controlled studies of conservative endometriosis surgery with or without adjunctive PN were included. Main outcomes were treatment failure (the proportion of women in which surgery failed to adequately resolve midline pain) and the frequency of operative and postoperative complications. A total of 7 studies with 8 group comparisons (3 randomized) representing 503 women (250 PN; 253 Control) were included. Over 34 months median follow-up, crude rates of treatment failure were 15.0% with PN and 40.9% with Controls (risk ratio = 0.43, 95% CI = 0.30 to 0.60, p < 0.001). The risk of postoperative constipation was higher with PN vs. Controls (12.5% vs. 0%, p = 0.024). No treatment group differences were observed for the risk of operative complications (0.6% vs. 0%, p = 0.498), reoperation (4.1% vs. 3.0%, p = 0.758) or urinary incontinence (5.0% vs. 0%, p = 0.195). Overall, in well-selected patients, conservative surgery with adjunctive PN may provide greater relief from midline pain and a similarly low rate of operative complications relative to conservative surgery alone but may increase the risk of constipation postoperatively. However, results were derived from mainly older and lower quality studies. Since then, surgical techniques to treat endometriosis have been improved and the effect of PN observed in prior studies should be confirmed in future studies in women in whom radical excision of deep infiltrating lesions is obtained.

Miller, S. A., et al. (2021). "Romosozumab: A Novel Agent in the Treatment for Postmenopausal Osteoporosis." Journal of Pharmacy Technology 37(1): 45-52.
	Objective: To review the safety and efficacy of romosozumab (Evenity) in the treatment of osteoporosis in women. Data Sources: An English-language search of PubMed and Medline (1966 to August 2020) was conducted using the keywords romosozumab, sclerostin inhibitor, AMG785, and osteoporosis. Manufacturer prescribing information, abstracts, fda.gov, and ClinicalTrials.gov data were incorporated for additional materials. In addition, a review of bibliographies of retrieved articles was performed to identify additional references. Study Selection/Data Extraction: Articles selected included those that described clinical studies of pharmacokinetics, efficacy, or safety of romosozumab. Data Synthesis: Romosozumab is a human monoclonal antibody that inhibits the action of sclerostin and is the first agent in its class to reach Phase III trials. Significant increases in bone mineral density and decreases in vertebral and hip fractures are demonstrated in Phase III trials. Favorable results led to its marketing approval in several countries. Major adverse cardiac events were observed in one clinical trial. Other adverse effects include arthralgia, headache, and injection site reactions. Place in Therapy: Romosozumab is the first agent to inhibit bone resorption and stimulate bone formation. Romosozumab should be reserved for postmenopausal women at highest risk for fracture and should be followed by an anti-resportive agent to maintain or further increase bone mineral density. This injectable agent should not be considered for women with a history of or at high risk of cardiovascular disease.Copyright © The Author(s) 2020.

Miller, V. M., et al. (2021). "Lessons from KEEPS: the Kronos Early Estrogen Prevention Study." Climacteric : the journal of the International Menopause Society 24(2): 139-145.
	The Kronos Early Estrogen Prevention Study (KEEPS) was a randomized, double-blind, placebo-controlled trial designed to determine the effects of hormone treatments (menopausal hormone treatments [MHTs]) on the progression of carotid intima-medial thickness (CIMT) in recently menopausal women. Participants less than 3 years from menopause and without a history of overt cardiovascular disease (CVD), defined as no clinical CVD events and coronary artery calcium < 50 Agatston units, received either oral conjugated equine estrogens (0.45 mg/day) or transdermal 17β-estradiol (50 µg/day), both with progesterone (200 mg/day for 12 days/month), or placebo pills and patches for 4 years. Although MHT did not decrease the age-related increase in CIMT, KEEPS provided other important insights about MHT effects. Both MHTs versus placebo reduced the severity of menopausal symptoms and maintained bone density, but differed in efficacy regarding mood/anxiety, sleep, sexual function, and deposition of β-amyloid in the brain. Additionally, genetic variants in enzymes for metabolism and uptake of estrogen affected the efficacy of MHT for some aspects of symptom relief. KEEPS provides important information for use of MHT in clinical practice, including type, dose, and mode of delivery of MHT recently after menopause, and how genetic variants in hormone metabolism may affect MHT efficacy on specific outcomes.

Miller, W. H., et al. (2022). "A phase I/II study of oral chk1 inhibitor LY2880070 in combination with low-dose gemcitabine in patients with advanced or metastatic ovarian cancer." Annals of Oncology 33(Supplement 7): S793-S794.
	Background: LY2880070 (LY) is an oral, selective competitive inhibitor of checkpoint kinase 1 (Chk1). LY and low-dose gemcitabine (LD GEM) was tolerable in advanced cancers. This combination has been assessed in advanced or metastatic high-grade serous ovarian cancer (HGSOC). Method(s): This two-part, open-label, multi-center study explored the safety, pharmacokinetics (PK), and anti-tumor activity of LY in patients with advanced or metastatic cancers. An expansion cohort was conducted in 27 patients with HGSOC. The primary objective of this Phase 2a cohort was to: 1) Characterize the dose-limiting toxicities (DLTs) and overall safety profile for LY+LD GEM in HGSOC; and 2) Evaluate the anti-tumor activity of LY + LD Gem. Patients received LY (50 mg b.i.d. X 5 days/week) + LD GEM (100 mg/m2) on days 1, 8, and 15 (optional) of a 21-day cycle. Result(s): The combination of LY with GEM was generally well tolerated. The most common related adverse events included fatigue nausea, vomiting, diarrhea, fever, dyspnea, neutropenia, and thrombocytopenia. Treatment-emergent adverse events in >40% of ovarian patients included vomiting, nausea, anemia, fever, decreased appetite, ALT increased, abdominal pain, and fatigue. DLTs included reduced platelet count (Gr2), fatigue (Gr3), diarrhea (Gr3), and thrombocytopenia (x2, Gr2). Two patients (7.4%) had partial response (PR). Fourteen patients (51.9%) had stable disease, one of whom had an unconfirmed PR. Eleven patients (40.7%) achieved disease control >= 12 weeks. Conclusion(s): This combination was generally tolerated in advanced or metastatic HGSOC. Further investigation is needed to better define biomarkers predictive of response in this patient population. Clinical trial identification: NCT02632448. Legal entity responsible for the study: Esperas Pharma Inc. Funding(s): Esperas Pharma Inc. Disclosure: W.H. Miller: Financial Interests, Personal, Other, Consultant fees: Merck, BMS, Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Personal, Other, Honoraria/speaker's bureau: BMS, Merck; Financial Interests, Personal, Other, Honoraria/Speaker's Bureau: Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Institutional, Research Grant, Grant: Merck, CIHR, CRS, Terry Fox Research Institute, SWCRF, CCSRI; Financial Interests, Institutional, Other, Clinical Trial: Merck, MiMic, Astellas, BMS, Novartis, GSK, Incyte, Pfizer, Sanofi, Ocellaris Pharma, Alkermes, Genentech, Array, Exelixis, VelosBio, Esperas Pharma. A.F. Shields: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc. D. Provencher: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc, Ocellaris Pharma Inc. L. Gilbert: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc. G. Shapiro: Financial Interests, Personal, Advisory Board: Pfizer, Eli Lilly, G1 Therapeutics, Roche, Merck KGaA/EMD-Serono, Sierra Oncology, Bicycle Therapeutics, Fusion Pharmaceuticals, Cybrexa Therapeutics, Astex, Almac, Ipsen, Bayer, Angiex, Daiichi Sankyo, Seattle Genetics, Boehringer Ingelheim, ImmunoMet, Asana, Artios, Atrin, Concarlo Holdings, Syros, Zentalis, CytomX Therapeutics, Blueprint Medicines; Financial Interests, Institutional, Invited Speaker: Exelixis, Cyteir, Clovis, Samumed, Abbvie, Incyte, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, CanBas, Cyclacel, Aileron, PUMA; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Esperas, Bayer, Lilly, Boehringer Ingelheim, Seattle Genetics, Syros; Other, Other, Patent: Dosage regimen for sapacitabine and seliciclib, issued to Geoffrey Shapiro and Cyclacel Pharmaceuticals: Cyclacel; Other, Pending patent: Compositions and Methods for Predicting Response and Resistance to CDK4/6 Inhibition, with Liam Cornell, PhD (Dana-Farber Cancer Institute): Dana-Farber Cancer Institute. A.M. Oza: Financial Interests, Institutional, Principal Investigator: Esperas Pharma, Ocellaris Pharma Inc. J. Spratlin: Financial Interests, Institutional, Principal Inve tigator: AstraZeneca, Taiho, Celgene, Incyte, Amgen, BMS. S. Lheureux: Financial Interests, Institutional, Principal Investigator: Esperas Pharma Inc. G. Bhat: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. S. Salvador: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. P. Nunes: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. S. Lau: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. I. Weiner: Financial Interests, Institutional, Project Lead: Esperas Pharma. J. Keene: Financial Interests, Institutional, Principal Investigator: Esperas Pharma. S. Zaknoen: Financial Interests, Personal, Advisory Role: Esperas Pharma, Ocellaris Pharma, Medikine, Atara, Mirati. P. Smith: Financial Interests, Personal, Other, Employee: Eli Lilly. J. Stille: Financial Interests, Personal, Other, Employee: Eli Lilly. D. Vincett: Financial Interests, Personal, Other, Employee: Ozmosis Research. Q.S. Chu: Financial Interests, Institutional, Principal Investigator: Alkermes, Bicycle, Exactis, GSK, Mirati, Ocellaris Pharma, Revolution Medicine, Treadwell, TP Therapeutics; Financial Interests, Personal and Institutional, Principal Investigator, Advisory Board: Amgen, Astellas, Astra Zenec, BMS, Boehringer Ingelheim, Eli Lilly, Esperas Pharma, Merck, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Abbvie, AnHeart, Eisai, J&J, Jazz, Roche, Sanofi, Takeda.Copyright © 2022 European Society for Medical Oncology

Miller-Graff, L. E., et al. (2022). "Examining the Efficacy of Prenatal Intervention in Reducing IPV Revictimization and Improving Maternal Mental Health: A Quasirandomized Controlled Trial of the Pregnant Moms' Empowerment Program (PMEP)." Journal of Consulting and Clinical Psychology 90(11): 884-898.
	Objective: The present study was a quasirandomized trial of the Pregnant Moms' Empowerment Program (PMEP) that examined the effects of the program on women's intimate partner violence (IPV) revictimization, depression, posttraumatic stress, and resilience. It was hypothesized that treatment would be associated with improvements across all of the indicated dimensions and that those women completing the module on violence and mental health would have particularly strong improvements. Method(s): Women who were currently pregnant, IPV-exposed, and at least 16 years of age were recruited and assigned to either a treatment or control condition. Participants (N = 137) completed four assessments (pretest [T1], posttest [T2], 3-months postpartum [T3], and 12-months postpartum [T4]). The key outcomes assessed included IPV (Revised Conflict Tactics Scales), depressed mood (Center for Epidemiological Studies Depression Scale), posttraumatic stress (PTSD Checklist for DSM-5), and resilience (Connor-Davidson Resilience Scale). Result(s): Results of multilevel models examining IPV revictimization indicated that treatment was associated with significantly fewer experiences of physical assault and sexual coercion at all follow-up interviews (T2, T3, and T4) and fewer IPV-related injuries at T3 and T4. In addition, treatment exposure was associated with statistically and clinically significant improvement in depression at T2 and T4. The intervention had limited efficacy in increasing women's self-reported resilience or in reducing symptoms of posttraumatic stress. Conclusion(s): Together, these data suggest that PMEP is a promising evidence-based intervention for pregnant, IPV-exposed women, and that the effects-particularly for IPV and depression- are likely to be sustained over time.Copyright © 2022 American Psychological Association

Millert-Kalińska, S., et al. (2023). "Epithelial Ovarian Cancer-Varied Treatment Results." Healthcare (Basel, Switzerland) 11(14).
	Ovarian cancer (OC) is the eighth most common cancer worldwide and is usually diagnosed in advanced stages. Despite many available data, no treatment results have been reviewed in Poland. This study enrolled 289 first-time patients treated between 2018 and 2021 by the Department of Oncology of the Poznań University of Medical Sciences (SKPP). The relationships among starting treatment in our centre, the type of first intervention, and the final decision were significant ( p < 0.001). Patients in the SKPP group were more likely to primarily have a laparoscopy and less likely to have an exploratory laparotomy. Neoadjuvant chemotherapy (NACT) after a laparotomy was less often a final decision among SKPP patients (9% vs. 22%), in contrary to NACT after a laparoscopy (23% vs. 4%). Factors affecting the shortening of progression-free survival (PFS) were an advanced stage of the disease, a histopathological diagnosis, the type of cytoreduction, and the final decision. Significance according to the final decision was revealed for PDS vs. NACT after a laparotomy ( p < 0.001) and for PDS vs. NACT after a laparoscopy ( p = 0.011). Our study supports the benefits of treating ovarian cancer in an oncology centre with a high patient throughput. Further observations might also answer the question about overall survival (OS).

Millet, N., et al. (2022). "ACCEPTANCE: protocol for a feasibility study of a multicomponent physical activity intervention following treatment for cervical cancer." BMJ Open 12(1): e048203.
	Introduction: Cervical cancer treatment can have life changing sequelae and be associated with poor short-term and long-term quality of life. Physical activity (PA; that is, bodily movement) is known to improve health outcomes and quality of life for cancer survivors, both physically and psychologically. To date, no interventions to increase PA following cervical cancer have been evaluated. This study aims to (1) determine the feasibility of conducting a PA intervention after cervical cancer and (2) to explore the acceptability of the programme and evaluation measures.; Methods and Analysis: The design is a pre study and post study design. Thirty participants aged between 18 and 60 years from the Midlands region, UK, who have completed primary treatment for cervical cancer at least 6 months previously and do not meet the national PA guidelines will be recruited. Identification of potential participants will take place through the University Hospitals of Leicester National Health Service (NHS) Trust. Participants will receive an intervention focused on increasing PA through the provision of education, action planning, goal setting, problem solving and self-monitoring of PA behaviour, particularly steps per day. Device assessed PA and questionnaires will be completed at baseline, week 6, week 12 and week 24. Feasibility will be assessed in terms of recruitment, retention, attrition, completion of measures and intervention compliance, for which specific feasibility criteria have been established. The process evaluation will explore the experiences and acceptability of the intervention components and evaluation measures.; Ethics and Dissemination: Ethical approval has been granted by the West of Scotland Research Ethics Committee 1 for this study. Results will inform intervention refinement for the design of a definitive pilot trial. These results will be disseminated via peer-reviewed publications and international conferences while input from a patient and public involvement (PPI) group will inform effective ways to circulate results among the wider community.; Trial Registration Number: ISRCTN16349793, Registered 30 September 2020.; Competing Interests: Competing interests: ELM has received research grants from Intuitive Surgical and Hope Against Cancer for unrelated work. ELM has received lecture fees for GlaxoSmithKlein and has served on the clinical advisory boards for Inivata and GlaxoSmithklein. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Milliken, S., et al. (2021). "Reducing the radicality of surgery for vulvar cancer: Are smaller margins safer?" Minerva Obstetrics and Gynecology 73(2): 160-165.
	INTRODUCTION: Vulvar cancer accounts for ~4% of all gynecological malignancies and the majority of tumors (>90%) are squamous cell (keratinizing, ~60% and warty/basaloid, ~30%). Surgical excision forms the foundation of treatment, with resection margin status being the single most influential factor when predicting clinical outcome. There has been a paradigm shift concerning surgical approaches and radicality when managing vulvar cancer within recent times, largely owing to a desire to preserve vulvar structure and function without compromising oncological outcome. As such the safety of the size of resection margin has been called into question. In this narrative review we consider the current literature on the safety of resection margins for vulvar cancer. EVIDENCE ACQUISITION: PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2005 to January 2020. The following search terms were used vulvar cancer surgery, vulvar squamous cell carcinoma, excision margins, adjuvant radiation. EVIDENCE SYNTHESIS: A pathological tumor margin of <8 mm has been widely considered to indicate "close" margins. This measurement after fixation of the tumor is considered comparable to a surgical resection margin of around 1cm, following an estimated 20% tissue shrinkage after formalin fixation and a 1-2cm clinical surgical margin in order to achieve the 8 mm final pathological margin. CONCLUSION(S): A surgical resection margin of 2-3mm does not appear to be associated with a higher rate of local recurrence than the widely used limit of 8 mm. As such the traditional practice of re-excision or adjuvant radiotherapy based on "close" surgical margins alone needs to be closely evaluated, since the attendant morbidity associated with these procedures may not be outweighed by oncological benefit.Copyright © 2021 Edizioni Minerva Medica.

Mills-Koonce, W. R., et al. (2023). "The Mood, Mother and Child Study: Protocol for a Prospective Longitudinal Study and Randomized Controlled Trial." JMIR Research Protocols 12: e51132.
	Background: Perinatal depression affects >400,000 mother-child dyads in the United States every year and is associated with numerous adverse maternal and child developmental outcomes. Previous research implicates the dysregulation of oxytocin and the hypothalamic-pituitary-adrenal (HPA) axis functioning in mothers and children as potential mechanisms mediating or moderating the transmission of risk associated with maternal depression.; Objective: The Mood, Mother and Child study will examine the psychobiological sources of risk and resilience within mother-child dyads affected by maternal depression. This manuscript describes (1) the study rationale and aims, (2) the research design and procedures and how they were altered in response to the COVID-19 pandemic, and (3) the data analysis plan to test the study hypotheses.; Methods: This is a prospective longitudinal study with an embedded randomized controlled trial that examines (1) correlations among postpartum depression and anxiety symptoms, maternal and child oxytocin and HPA axis functioning, and child developmental outcomes and (2) the causal relationship between exogenous oxytocin and HPA reactivity. This study is funded by the National Institute of Child Health and Human Development with institutional review board approval.; Results: Recruitment and data collection have commenced, and the expected results will be available in 2024. Analyses are presented for testing the proposed hypotheses.; Conclusions: The unique combination of a prospective longitudinal research design with an embedded randomized controlled trial will allow the Mood, Mother and Child study to apply a developmental lens to the study of maternal depression and anxiety symptoms from birth to middle childhood and the psychobiological mechanisms promoting risk and resiliency for both mother and child outcomes. This will be the first study that simultaneously evaluates (1) the role of oxytocin using multiple methodologies, (2) the causal relationships between exogenous oxytocin and HPA axis functioning among mothers with differing levels of depression and anxiety symptoms, and (3) the multiple mediating and moderating roles of parenting behaviors and maternal and child psychobiological characteristics. The goals of these aims are to provide insights into the psychobiological effects of oxytocin in women and inform future clinical trials to treat perinatal mood disorders.; Trial Registration: ClinicalTrials.gov NCT03593473; https://classic.clinicaltrials.gov/ct2/show/NCT03593473.; International Registered Report Identifier (irrid): DERR1-10.2196/51132. (©W Roger Mills-Koonce, Karen Grewen, Nisha Gottredson O’Shea, Brenda Pearson, Chelsea Grace Strange, Samantha E Meltzer-Brody, Jerry Dolph Guintivano, Alison M Stuebe. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.10.2023.)

Milovic-Kovacevic, M., et al. (2023). "Olaparib as a first-line maintenance treatment for BRCA-positive ovarian cancer patients: Single-institution experience." Libri Oncologici 51(Supplement 2): 76-77.
	Introduction: We all acknowledge that olaparib is most effective when used as maintenance therapy following a positive response to platinum-based regimens in patients with newly diagnosed advanced high-grade serous ovarian cancer (HGSOC). Purpose(s): The aim of this paper is to present our firsthand experiences with utilizing olaparib as a first-line treatment. Method(s): At the Institute of Oncology and Radiology of Serbia, we treated a total of 14 patients, with 7 patients testing positive for BRCA2 and another 7 patients testing positive for BRCA1 mutations. BRCA positivity was confirmed in all patients through the analysis of somatic mutations, and in one patient a germline BRCA mutation was additionally confirmed by a blood analysis. Out of the total patients, nine were diagnosed with FIGO stage IIIa, while five patients were diagnosed with stage IVa, based on positive cytology of pleural effusion. Result(s): The majority of our patients underwent surgery with a significant residual tumor burden. Out of 9 patients who underwent surgery, 3 patients achieved no evidence of disease (NED), while 5 patients were initially treated with neoadjuvant systemic therapy for inoperable disease due to large tumor burden. After a follow-up period of max22-month, the progression-free survival (PFS) was observed to be 12 months. The most frequently achieved response was partial remission in 8 patients, with 3 patients maintaining NED stadium. One patient had rapid progression of the disease, while 2 patients achieved complete remission. Two patients experienced a severe level of grade 3 anemia, and one patient had grade 3 thrombocytopenia. These listed toxicities necessitated a temporary interruption of therapy and a subsequent dose reduction after correcting the hematological toxicity. Two patients exhibited grade 2 renal impairment, which was effectively managed through appropriate hydration measures. Conclusion(s): The limitations of our analysis lie in the small sample size and the relatively short duration of patient follow-up. Furthermore, compared to the existing literature data and the SOLO1 study, the patients included in our analysis exhibited a notably higher tumor burden and disease extent, and consequently, they bear greater resemblance to the patients enrolled in the PAOLA1 study. Despite these limitations, our analysis clearly demonstrates significant effectiveness and excellent outcomes with adequate safety profiles in ovarian cancer patients with BRCA mutations who received olaparib maintenance therapy following favorable responses to platinum-based therapy.

Min, J., et al. (2022). "Clinical outcomes of fetal ovarian masses diagnosed by prenatal ultrasonography and literature review." Medicine 101(41): e30962.
	With the advancement of prenatal examination technology, more and more fetus with ovarian masses are diagnosed. However, whether such children need intervention measures after delivery, there is no more unified diagnosis and treatment measures in the world. In this study, postnatal data and clinical outcome of fetal diagnosed with ovarian masses were analyzed. We also combined with relevant literature to explore the postpartum intervention measures and timing of such children. A total of 57 cases of abdominal masses from the reproductive system were included in the study. These children were diagnosed with ovarian masses after birth. We collected from 2012 to 2020, the prenatal examination revealed the presence of abdominal masses from the reproductive system, and diagnosis was confirmed by imaging examinations after childbirth. We counted the fetal period data of these children, compared the changes in the postnatal pathology and intervention measures. A total of 57 cases of ovarian masses were diagnosed prenatally, 1 case was lost to follow-up, and 56 cases were finally included in the study. After birth a total of 21 cases of ovarian masses were treated conservatively, of which 18 cases resolved spontaneously during the follow-up process, with an average follow-up period of 30.88 ± 18.16 weeks. There were statistically significant differences in the nature and the maximum diameter of the mass between the two groups receiving conservative treatment or surgical treatment after delivery (P < .05).Univariate and multivariate Logistic regression analysis showed that there were significant differences in the nature and diameter of the mass between two groups (P < .05). In addition, we divided the children undergoing postpartum surgery into a laparoscopic surgery group and a conventional open surgery group. Through data analysis, we found that there were statistically significant differences in the age of operation, operation time, and hospitalization days in the two groups of these children (P < .05). Children diagnosed with ovarian masses prenatally generally have a good prognosis. For these children, the treatment plan should be developed according to the child general condition. If child with ovarian mass is treated with surgery, the preservation of ovarian tissue should be emphasized regardless of the size, nature, and torsion of the mass.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Min, L., et al. (2022). "Effectiveness of intravaginal electrical stimulation combined with electromyography biofeedback-mediated pelvic floor muscle training for postpartum symptomatic pelvic organ prolapse: protocol for the PROSPECT randomized trial." Trials 23(1): 131.
	Background: Pelvic organ prolapse (POP) is seen in up to 30-70% of women presenting for routine gynecology care and 10% of women suffering from bothersome POP symptoms. Vaginal childbirth is one of the most prominent contributing factors for POP. Pelvic muscle training (PFMT) is considered effective to improve mild to moderate POP symptoms. In addition, higher-intensity, supervised PFMT aided by biofeedback and electrical stimulation may confer greater benefit. However, the long-term efficacy of the PFMT combined with electromyography biofeedback is unknown, which indicates the need for further evidence.; Methods: This multicenter randomized controlled trial compares the effectiveness and cost-effectiveness of conventional PFMT versus biofeedback-mediated PFMT plus neuromuscular electrical stimulation (NMES) for postpartum symptomatic POP women. The primary outcome is the proportion of patients with the improvement of at least one POP-Q stage at 36 months after randomization. The primary economic outcome measure is incremental cost per quality-adjusted life year at 36 months. Two hundred seventy-four women from four outpatient medical centers are randomized and followed up with pelvic floor examination, questionnaires, and pelvic ultrasonography imaging. All participants are arranged for three appointments over 12 weeks. NMES and electromyography biofeedback via intravaginal probe are added to PFMT for participants in the biofeedback-mediated PFMT group. Group allocation could not be blinded from participants and healthcare staff that deliver intervention but remain masked from medical staff that carry out PFM assessment. An intention-to-treat analysis of the primary outcome will estimate the difference of the proportion of POP-Q stage improvement between the trial groups right after the intervention, and during the follow-up until 36 months, using the chi-square test and multilevel mixed models respectively. A logistic regression analysis was used for adjusting for important baseline variables that are unbalanced.; Discussion: The trial results will provide evidence of the effectiveness of electromyography biofeedback-mediated PFMT in improving women's POP-Q staging, quality of life, and cost-effectiveness.; Trial Registration: CCTR Registry ChiCTR210002171917 . Registered on March 6, 2019. (© 2022. The Author(s).)

Min, L., et al. (2023). "Two year follow-up and comparison of pelvic floor muscle electromyography after first vaginal delivery with and without episiotomy and its correlation with urinary incontinence: A prospective cohort study." Acta Obstetricia et Gynecologica Scandinavica 102(2): 200-208.
	Introduction: Few prospective studies have revealed the long-term neuromuscular alterations of pelvic floor after vaginal delivery. The aim of this study was to evaluate the impact of episiotomy on the electrical activity of pelvic floor muscle 2 years following vaginal delivery, and explore the relation between surface electromyography (sEMG) amplitudes and urinary incontinence. Material(s) and Method(s): A total of 427 primiparous women with full-term singleton vaginal delivery were included in the cohort and 362 with no further births within the 2 year follow-up completed observations. Of these, 200 underwent episiotomy and 162 underwent nonepisiotomy. Clinical demographic characteristics, vaginal EMG variables and urinary incontinence-specific questionnaire scores were collected at 6 weeks, 6, 12 and 24 months after childbirth, respectively. Primary outcomes were the comparison of sEMG values between the episiotomy and nonepisiotomy groups throughout 2 years. Secondary outcomes were the correlation between sEMG of both groups and the incidence and severity of urinary incontinence. Spearman's correlation analysis, Kruskal-Wallis test and ANOVA with Bonferroni correction were used to analyze the variables. Result(s): Amplitude of maximal fast and endurance contractions on sEMG in the episiotomy group was significantly lower than the nonepisiotomy counterpart. Such difference of sEMG persisted for a long period after birth: endurance contraction, 33.12 +/- 8.92 vs 35.085 +/- 9.98, p < 0.01 at 24 months, and fast contraction, 36.53 +/- 8.87 vs 39.05 +/- 9.98, p = 0.01 at 12-month. Although there was no significant difference in incidence and severity of urinary incontinence between both groups, a negative correlation existed between EMG values of muscle contraction and urinary incontinence symptoms throughout. Conclusion(s): Primiparous women delivered with episiotomy demonstrated lower contractile sEMG activity of pelvic floor muscle in the long term. The lower sEMG values of fast contraction were associated with urinary incontinence symptoms.Copyright © 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Min, M., et al. (2022). "Effect of orlistat during individualized comprehensive life-style intervention on visceral fat in overweight or obese PCOS patients." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(8): 676-680.
	Objective To investigate the effect of orlistat combined with drospirenone/ethinylestradiol tablets (DRSP/EE) on the visceral fat area (VFA) compared to DRSP/EE-alone in overweight or obese patients with polycystic ovary syndrome (PCOS). Methods 90 PCOS patients [body mass index (BMI) ≥24kg/m 2 ] were recruited for a prospective, open-label, 1:2 paired 3-monthly study. All were included during the per-protocol defined recruitment time and numbered according to the entry-order: group-1: No.1-60, orlistat plus DRSP/EE; group-2: No.61-90, DRSP/EE-alone. Both groups received the same comprehensive intervention in terms of individualized, standardized management and lifestyle monitoring such as diet and exercise. Primary study-endpoint was VFA, secondary endpoints were anthropometric indices, sex hormones and glucolipid metabolism. Within- and between-group analyses were performed. Results VFA [cm 2 ] in group-1 after treatment decreased significantly ( p = 0.001), and the between-group comparison was highly significant ( p = 0.001). Body weight, hip circumference (HC), BMI, body fat (BF), free testosterone (FT) and low-density lipoprotein-cholesterol (LDL-C) significantly decreased in both groups (within-group analysis); the decrease in group-1 was significantly greater than in group-2 ( p < 0.05). Systolic and diastolic blood pressure (SBP/DBP) and fasting plasma glucose (FPG) in group-1 were significantly decreased, significantly more in group-1 than in group-2 ( p < 0.05). Conclusion This study is the first to investigate the effect of orlistat combined with DRSP/EE in overweight or obese PCOS patients compared with using DRSP/EE-alone. Orlistat combined with DRSP/EE was better than using DRSP/EE-alone in reducing VFA, body weight, FT, BP and FPG, which provides evidence for the choice of rational drug use in clinical practice.

Min, X., et al. (2023). "The effects of cognitive behavioral intervention in womon with polycystic ovary syndrome&#xff1a;A systematic review and meta-analysis."
	
Min, Y. and Y. Jia-xin (2021). "Impact of Adjuvant Chemotherapy for Stage I clear cell ovarian carcinoma: A systematic review and meta-analysis."
	
Min, Y. and Z. Zhang (2022). "Hysterectomy or/and lymphadenectomy for the survival of patients with primary endometrial cancer: a cohort study using the SEER database." Biotechnology & Genetic Engineering Reviews: 1-19.
	In order to provide a clinical reference for endometrial cancer treatment, this retrospective cohort study aimed to assess and compare the survival of endometrial cancer patients undergoing hysterectomy versus lymphadenectomy and hysterectomy combined with lymphadenectomy. The Surveillance, Epidemiology, and End Results (SEER) database provided data on patients with primary endometrial cancer enrolled between 1975 and 2016. The longest follow-up time was ten years, and the median follow-up time was 51.00 months. The outcomes were overall survival (OS) and cancer-specificsurvival (CSS). COX models were constructed to assess the relationship between the three surgical methods and OS or CSS. Subgroup analyses were conducted based on American Joint Committee on Cancer (AJCC) stage and menopausal status. Totally 134,597 patients were included. In stage IV, the lymphadenectomy group had significantly worse OS than the hysterectomy group (HR = 1.330, 95%CI = 1.101-1.606). The hysterectomy combined with lymphadenectomy group had similar OS to the hysterectomy group (HR = 1.183, 95%CI = 0.996-1.405). Regarding CSS, no significant differences were found between the hysterectomy and lymphadenectomy groups (HR = 1.267, 95%CI = 0.996-1.610), and between the hysterectomy and hysterectomy combined with lymphadenectomy groups (HR = 1.186, 95%CI = 0.953-1.476) in stage IV. For postmenopausal women, lymphadenectomy (HR = 1.655, 95%CI = 1.495-1.831) and hysterectomy combined with lymphadenectomy (HR = 1.129, 95%CI = 1.038-1.228) were associated with significantly decreased OSthan hysterectomy. For CSS among postmenopausal women, significant declines inCSS were found in the lymphadenectomy (HR = 2.264, 95%CI = 1.957-2.619) and hysterectomy combined with lymphadenectomy (HR = 1.419, 95%CI = 1.260-1.599) groups versus the hysterectomy group. Hysterectomy may serve as a decision-making reference for clinicians in treating patients in stage IV or after menopause, combined with clinical experience and patients' wishes.

Minareci, Y. and S. Portakal (2021). "RFSH versus transvaginal hydrolaparoscopic ovarian drilling in patients with polycystic ovary syndrome resistant to ovulation induction." Journal of Reproductive Medicine 66(1‐2): 40‐46.
	OBJECTIVE: To compare outcomes of recombinant follicle‐stimulating hormone (rFSH) treatment with transvaginal hydrolaparoscopic ovarian drilling (THLOD) procedure in patients with polycystic ovary syndrome (PCOS) resistant to ovulation induction with clomiphene citrate (CC). STUDY DESIGN: A total of 156 patients were eligible for inclusion in the present study, of whom 76 were allocated to the THLOD strategy and 80 were allocated to the rFSH strategy. For the THLOD group, each ovary was randomly ablated at 10‐15 points at the anterolateral side, depending on its size, and if anovulation persisted for 8 weeks after electrocautery or the patient became anovulatory again, treatment was started with 50 mg clomiphene citrate. For the rFSH group, ovulation induction was started on cycle day 3 using 75 IU rFSH daily. RESULTS: The rate of live birth in the rFSH strategy was 67.5%, and the rate of live birth in the THLOD strategy was 63.2% (p=0.6). However, time to first successful ovulation and conception were found to be significantly shorter in the rFSH strategy arm. There was no major complication related to surgical procedure, and minor complications occurred in 8 patients (5%). CONCLUSION: The THLOD procedure, as compared to rFSH therapy, appears to be an unfavorable option for the treatment of patients with CC‐resistant PCOS. Since THLOD procedure has many disadvantages, we recommend rFSH therapy as the treatment of first choice in this patient subgroup.

Minareci, Y., et al. (2022). "Prolongation of Neoadjuvant Chemotherapy before Surgery: Seeking the Optimal Number of Cycles in Serous Ovarian Cancer." Chemotherapy 67(1): 1-11.
	Aim: The optimal number of neoadjuvant chemotherapy (NACT) cycles is unclear in epithelial ovarian cancer. Our study aimed to evaluate the effect of the number of NACT cycles before interval debulking surgery on survival.; Methods: Data of 221 patients with advanced-stage serous epithelial ovarian cancer (EOC) were retrospectively evaluated. The patients were divided into groups as who received 3 cycles of NACT (group A), 4-5 cycles of NACT (group B), and 6 cycles of NACT (group C).; Results: There were 67 (30%) patients in group A, 70 (32%) in group B, and 84 (38%) in group C. Median overall survival (OS) was 61 (range 43-79) months for group A, 44 (range 36-52) months for group B, and 39 (range 27-50) months for group C. In addition, median disease-free survival (DFS) was 23.1 (range 8.5-32.1) months for group A, 19.2 (range 10.1-28.4) months for group B, and 21.5 (range 16-27) months for group C. Patients receiving >3 NACT cycles had worse OS than patients who received 3 NACT cycles (for group A vs. B, p = 0.018; for group A vs. C, p = 0.049). However, in terms of DFS, patients receiving 3 NACT cycles had no statistically significant difference compared to patients who received >3 NACT cycles.; Conclusions: Patients with advanced-stage serous EOC who received more than 3 cycles of NACT had poor OS. However, there was no statistical difference in terms of DFS. In addition, >3 cycles of NACT did not increase the probability of achieving complete cytoreduction at the time of surgery. (© 2021 S. Karger AG, Basel.)

Minchala-Urgiles, R. E., et al. (2020). "Breastfeeding as an alternative for the prevention of maternal and infant diseases: Systematic review." Archivos Venezolanos de Farmacologia y Terapeutica 39(8): 941-947.
	Breastfeeding is one of the most effective ways to ensure maternal and child health and survival. Objective(s): To analyze, through a bibliographic review, breastfeeding as an alternative for the prevention of maternal and infant diseases. Methodology: A systematic review was carried out on scientific bases such as LILACS, Pubmed, UNAM, Dialnet, Progress in Health Sciences, Revista Enfermeria Global, Medlin-ePlus, Revista Enfermeria CyL, Redalyc, during the period 2015-2020, including information in Spanish and English. Result(s): The literature search reported a total of 16475, but after applying selection criteria and evaluative reading, 31 ar-ticles were included for analysis because of their relevance and contribution to meeting the objective. Conclusion(s): Breastfeeding at the infant level prevents infectious diseases of the digestive and respiratory tract in the short and medium term and overweight and hypertension in the long term. At the maternal level the benefits are: prevention of hemorrhages, anemia, breast and ovarian cancer, type II diabetes, hypertension and cardiovascular diseases.Copyright © 2020, Venezuelan Society of Pharmacology and Clinical and Therapeutic Pharmacology. All rights reserved.

Ming, X., et al. (2023). "Pregnancy outcomes after uterine artery embolization for women: A systematic review and meta-analysis with trial sequential analysis."
	
Ming-Li, S., et al. (2021). "Metformin versus laparoscopic ovarian drilling to treat patients with clomiphene citrate-resistant polycystic ovary syndrome: A systematic review and meta-analysis."
	
Ming-Zhu, J. and D. Wen (2023). "Evaluation of Interventions in Patients With Vulvodynia/Vestibulodynia: A Systematic Review and Meta-analysis."
	
Minh, C. and H.-C. Sarah (2024). "Improving the understanding of surgical intervention of endometriosis and its effect on fertility."
	
Minnaar Carrie, A., et al. (2022). "Effects of Modulated Electro-Hyperthermia (mEHT) on Two and Three Year Survival of Locally Advanced Cervical Cancer Patients." Cancers 14(3).
	(1) Background: Modulated electro-hyperthermia (mEHT) is a mild to moderate, capacitive-coupled heating technology that uses amplitude modulation to enhance the cell-killing effects of the treatment. We present three year survival results and a cost effectiveness analysis from an ongoing randomised controlled Phase III trial involving 210 participants evaluating chemoradiotherapy (CRT) with/without mEHT, for the management of locally advanced cervical cancer (LACC) in a resource constrained setting (Ethics Approval: M120477/M704133; ClinicalTrials.gov ID: NCT033320690). (2) Methods: We report hazard ratios (HR); odds ratio (OR), and 95% confidence intervals (CI) for overall survival and disease free survival (DFS) at two and three years in the ongoing study. Late toxicity, quality of life (QoL), and a cost effectiveness analysis (CEA) using a Markov model are also reported. (3) Results: Disease recurrence at two and three years was significantly reduced by mEHT (HR: 0.67, 95%CI: 0.48-0.93, p = 0.017; and HR: 0.70, 95%CI: 0.51-0.98, p = 0.035; respectively). There were no significant differences in late toxicity between the groups, and QoL was significantly improved in the mEHT group. In the CEA, mEHT + CRT dominated the model over CRT alone. (4) Conclusions: CRT combined with mEHT improves QoL and DFS rates, and lowers treatment costs, without increasing toxicity in LACC patients, even in resource-constrained settings.

Minto, C. A., et al. (2022). "A comparative analysis of the long-term effects of cancer therapy on survivors enrolled in the University Cancer Center Hamburg (UCCH) Clinical Survivorship Registry: a cohort study." Oncology Research and Treatment 45(Supplement 3): 208.
	Background: As cancer rates increase and mortality decreases, the number of survivors will rise. Cancer therapy causes lasting side-effects that impact well-being. This study aims to report prevalences of distress, depression, anxiety, fatigue and level of unmet needs; and assess the influence of age, sex, primary diagnosis, treatment modality (TM) and time since diagnosis (TSD). Method(s): Subjects were recruited from the UCCH survivorship program and at first appointment completed 5 questionnaires (DT, SCNS-SF34, PHQ-9, GAD-7 & FACIT-F). Demographics and prevalences were reported for the group and selected cohorts (age: 18-39, 40-64, 65+; sex; primary diagnosis: lymphoma, leukemia, gastrointestinal, gynecological, sarcoma, other; TM: multimodal, local, systemic; TSD: 0-2, 3-5, 6-10, 10+ years). Multivariable linear/logistic regression and pairwise comparison were run on cohorts to assess the odds of reporting clinically relevant outcome levels. Result(s): From Jan. 2015 to Mar. 2020 449 survivors were screened - 435 included. Overall, 57.2% reported clinically relevant distress levels. For depression: mild (30.1%), moderate (15.4%), moderately-severe (5.3%) and severe (1.8%) symptoms were reported. 78% reported the likely presence of an anxiety disorder. 29.2% reported clinically significant fatigue. Mean summated Likert scores +/-SD for unmet needs: psychological 19.97+/-10.497, health systems & information 23.62+/-13.939, physical & daily living 9.19+/-4.607, patient care & support 8.30+/-4.592 and sexuality 5.01+/-3.062. The impact analysis indicated that age and primary diagnosis had the greatest influence, followed by sex, TSD and TM. Discussion(s): In most outcomes over half of respondents reported clinically relevant levels, showing how strongly the long-term effects of therapy affect survivors. Whilst the impact analysis provides key insights into what did, and perhaps more interestingly, did not strongly influence the outcomes. Conclusion(s): Based on the findings, future research could seek to better understand the influence of age, sex, diagnosis, TM and TSD.

Minxiu, C. and W. Wenwen (2023). "Effect of pelvic floor functional exercise combined with psychological support based on root cause analysis on pelvic floor function and postpartum depression in primiparas." Revista de Psiquiatria Clinica 50(1): 37-42.
	Objective: To examine the impact of psychological support and pelvic floor functional exercise on primiparous women's postpartum depression using root cause analysis. Method(s): The subjects of this study consist of 92 women who gave birth at our hospital between January 2020 and March 2022. In accordance with the variations in nursing approach, they were separated into a control group (n=43) and an intervention group (n=49). Standard postpartum care was provided to the control group; Functional pelvic floor exercises and psychological assistance based on root because analysis was provided to the intervention group. To observe and compare the effect of different nursing methods on primiparas in two groups. Result(s): Age, gestational age, body mass index, and educational levels were all compared between the two groups using statistical software and both were found to have a P-value greater than 0.05, indicating that they were statistically equivalent. Tension in the pelvic floor muscles, urine habits, levels of anxiety and sadness, and psychological resilience were all similar between the two groups before breastfeeding was introduced (P>0.05). When comparing the two groups immediately following nursing, the intervention group significantly outperformed the control group on a number of measures, including the Oxford, the VRP, the VSP, and the duration of vaginal contractions; the ICI-Q-SF scores were lower; the HAMA and HAMD scores were lower; and the intervention group significantly outperformed the control group on a number of other measures, including optimism, tenacity, self-improvement, and total score. There was a statistically significant (P<0.05) improvement in satisfaction levels between the intervention group and the control group. Conclusion(s): Primiparas benefit greatly from a combination of pelvic floor functional training and psychological support based on the root cause analysis technique, which shows promise as a clinical intervention for enhancing both pelvic floor function and mental health.Copyright © 2023, Universidade de Sao Paulo. Museu de Zoologia. All rights reserved.

Mir Suhail, A., et al. (2022). "Evaluation of the Safety and Efficacy of Ormeloxifene, a Selective Estrogen Receptor Modulator and Medroxyprogesterone Acetate in Women with Non-Structural Abnormal Uterine Bleeding: A Randomized Clinical Trial." Medicina (Kaunas, Lithuania) 58(11).
	Background and objectives: Abnormal uterine bleeding is a significant clinical and gynaecological concern that necessitates its safe and effective treatment. The present study aims to compare the cost-effectiveness, safety, efficacy, and health-related quality of life of ormeloxifene with medroxyprogesterone acetate in women with non-structural abnormal uterine bleeding. Materials and Methods: A prospective, randomized, single-blinded clinical trial of 367 patients was carried out at a tertiary care hospital for a period of one year from 5 January 2019 to 4 January 2020. Patients were randomized into two groups for administering ormeloxifene and medroxyprogesterone acetate for a 3-month treatment duration and were evaluated by laboratorial investigations like anaemic status, bleeding duration, endometrial thickness, pictorial blood loss assessment chart (PBLAC) score, and patient’s medical and medication history. Health-related quality of life was assessed using short form survey-36 (SF-36) questionnaire scale. Cost-effectiveness was determined on the basis of the three-month treatment regimen. Results: The mean duration of bleeding reduced from 16.88 ± 6.46 to 7.76 ± 1.55 in the ormeloxifene group and from 15.91 ± 5.04 to 8.7 ± 1.91 (p < 0.001) in the medroxyprogesterone acetate. Similarly, mean haemoglobin increased from 8.56 ± 0.77 to 10.1 ± 0.087 g/dL and from 8.60 ±0.97 to 9.551 ± 0.90 g/dL (p < 0.001), and endometrial thickness showed a reduction from 8.52 ± 1.61 mm to 6.92 ± 1.68 mm and from 8.40 ± 2.09 mm to 7.85 ± 2.0 mm (p < 0.001) in the ormeloxifene and medroxyprogesterone acetate groups, respectively. PBLAC score reduced from 289.92 ± 42.39 to 128.11 ± 33.10 and from 287.38 ± 40.94 to 123.5 ± 29.57 (p < 0.001) in these groups, respectively. Health-related quality of life improved in the ormeloxifene group more than the medroxyprogesterone group, which was evidenced by SF-36 scale parameters (physical function, energy/fatigue and pain) that changed from 24.39, 12.99, 6.25 to 28.95, 18, 9 and from 25.41, 13.6, 7.1 to 27.02, 16, 8.3 in the ormeloxifene and medroxyprogesterone acetate groups, respectively. Conclusions: The study concludes that both medroxyprogesterone acetate and ormeloxifene are safe and efficacious in controlling abnormal uterine bleeding, but ormeloxifene was the better of the two in terms of cost effectiveness, reduction in pictorial blood loss assessment score, endometrial thickness, bleeding duration (days), increase in haemoglobin concentration (g/dL) and improvement in the quality of life.

Mi-Ra, O., et al. (2022). "Systematic review and meta-analysis of the placebo effects on menopausal symptoms in dietary supplements: Implications for research and clinical practice." PROSPERO International prospective register of systematic reviews.
	Review question Systematic review and meta-analysis of the placebo effects on menopausal symptoms in dietary supplements: Implications for research and clinical practice. Searches A literature search will be conducted according to each study design (RCTs) using the following search terms:(“menopaus*”) AND (“supplement*” OR “complement*” OR “botanic*” OR “phyto*” OR “herb*”) AND (“placebo”) AND (“clinical Trial” OR “clinical study” OR “RCT” OR “controlled trial” OR “controlled study” OR “human trial” OR “human study”).We will search the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Google Scholar in order to identify relevant trials. Search will be conducted to identify relevant articles published between January 2000 and March 2022. In the Cochrane review, studies published before 2000 were assessed as having a high risk of bias than articles published after 2000. Therefore, we will only include studies published after 2000. Types of study to be included All available randomized controlled trials (RCTs) will be included and languages will be limited to English Condition or domain being studied Menopausal symptoms, Menopausal syndrome Participants/population Inclusion: Women with any type of menopausal symptom, that is peri- and post-menopausal symptom. Exclusion: We will explore common menopausal symptoms, excluding conditions which could impair an individual’s ability to monitor their symptoms accurately, or could lead to fatality, hospitalization. Intervention(s), exposure(s) We will accept any type of placebo, by and period, administered for the relief of menopausal symptom. Comparator(s)/control Any type of dietary supplements Main outcome(s) Primary outcomes - Kupperman’s index (KI), menopause rating scale (MRS), and hot flushes Measures of effect Mean difference Additional outcome(s) Secondary outcomes - Greene Climacteric Scale (GCS), Menopause specific quality of life (MENQOL) - Cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol - Estradiol Measures of effect Mean difference Data extraction (selection and coding) Study selection: Two reviewers will independently screen the search results. The first based on title and/or abstract and the second based on full text. Any disagreements will be resolved by consensus. If consensus is not reached, a third reviewer will be consulted to make a decision. Data extraction: Two reviewers will independently extract data using a standardized data extraction format, and inconsistent results will be resolved through confirmation and discussion of the original paper. The following data will be extracted: first author, publication year, study design, participant’s characteristics, types of interventions, and outcomes, etc. Risk of bias (quality) assessment Two reviewers will independently assess the risk of bias in included studies using the Cochran’s Risk of Bias tool. This tool assesses risk of biases in the trials based on random sequence generation, allocation concealment, blinding of the participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Strategy for data synthesis Meta-analysis will be performed using Cochrane software Review Manager 5.4, otherwise descriptive analysis will be performed. Data will be presented by weighted mean difference with its 95% CI for continuous outcomes. I² statistic test will be used to estimate the percentage of heterogeneity between the studies. Meta-analysis will be performed according to a fixed-effects model, but if there are heterogeneity (I²>50%), cause of the heterogeneity will be investigated if possible. In addition, a random effects model will be performed if clinically appropriate. Analysis of subgroups or subsets If necessary, subgroup analyses will be conducted according to 1) stage of menopause, 2) estrogen levels. Contact details for further information Mi-Ra Oh mroh@jbctc.org Organisational affiliation of the review Jeonbuk National University Hospital Review team members and their organisational affiliations Dr Mi-Ra Oh. Clinical Trial Center for Functional Foods, Chonbuk National University Hospital Dr Soo Hyun Park. Korea Food Research Institute Professor Byung-Hyun Park. Chonbuk National University Medical School Professor Soo-Wan Chae. Biomedical Research Institute of Chonbuk National University Hospital Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 01 April 2022 Anticipated completion date 30 September 2022 Funding sources/sponsors No funding Conflicts of interest Language English Country South Korea Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Dietary Supplements; Humans; Isoflavones; Menopause; Placebo Effect Date of registration in PROSPERO 05 May 2022 Date of first submission 05 April 2022 Stage of review at time of this submission The review has not started

Mirajkar, V. (2023). "Study on the Management of Heavy Menstrual Bleeding by Low Dose Dexamethasone." International Journal of Pharmaceutical and Clinical Research 15(5): 198-206.
	Introduction: Menstruation that is so severe it interferes with a woman's physical, emotional, social, and material well-being is referred to as heavy menstrual bleeding (HMB). Estimates place the prevalence of excessive menstrual bleeding in impoverished countries at 4-9%. It has figured out the causes of HMB and around 48% of patients that are sent to secondary care do not have any evident pathology. Aims and objectives: The purpose of this research study has been explored to the management of heavy menstrual bleeding by low dose dexamethasone. Method(s): This prospective Randomized Controlled Trial enrolled 100 female patients with heavy menstrual bleeding (HMB) from May 2022 to April 2023. Patients were randomly assigned to receive either placebo or dexamethasone, a synthetic glucocorticoid, in different dosages (0.4 mg, 0.8 mg, 1 mg, 1.2 mg, 1.5 mg, or 1.8 mg) during the luteal phase of three menstrual cycles. Menstrual blood loss was evaluated using a lab-validated method. Inclusion and exclusion criteria were applied, and statistical analysis was performed using SPSS 25 software, including Chi-square and ANOVA tests. Significance level was set at p<0.05. Result(s): The researcher was divided into two different groups of patients such as placebo and dexamethasone with 20 and 80 patients respectively. Furthermore, the age categories of patients are from 22 to 56 years old. Again, the mean blood loss during menstruation is high around 136.5 mL of dexamethasone. The greatest impact was seen at a 25 mL reduction in menstrual blood loss with the 1/8 mg total daily dose, with a 95% credible interval of 1 to 49 mL. The posterior odds for any benefit over placebo, or at least a 10 mL benefit, for this dose, were 0.98 and 0.89, respectively. Conclusion(s): The study has concluded that 0.8mg of dexamethasone taken twice daily for 5 days during the luteal phase of the menstrual cycle would reduce menstrual blood does volume.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Miralpeix, E., et al. (2023). "Prehabilitation in an ERAS program for endometrial cancer patients: impact on post-operative recovery." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(4): 528-533.
	Objectives: Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways that aim to reduce stress response and improve perioperative outcomes. However, literature is limited regarding the impact of ERAS and prehabilitation in gynecologic oncology surgery. The aim of this study was to assess the impact of implementing an ERAS and prehabilitation program on post-operative outcomes of endometrial cancer patients undergoing laparoscopic surgery.; Methods: We evaluated consecutive patients undergoing laparoscopy for endometrial cancer that followed ERAS and the prehabilitation program at a single center. A pre-intervention cohort that followed the ERAS program alone was identified. The primary outcome was length of stay, and secondary outcomes were normal oral diet restart, post-operative complications and readmissions.; Results: A total of 128 patients were included: 60 patients in the ERAS group and 68 patients in the prehabilitation group. The prehabilitation group had a shorter length of hospital stay of 1 day (p<0.001) and earlier normal oral diet restart of 3.6 hours (p=0.005) in comparison with the ERAS group. The rate of post-operative complications (5% in the ERAS group and 7.4% in the prehabilitation group, p=0.58) and readmissions (1.7% in the ERAS group and 2.9% in the prehabilitation group, p=0.63) were similar between groups.; Conclusions: The integration of ERAS and a prehabilitation program in endometrial cancer patients undergoing laparoscopy significantly reduced hospital stay and time to first oral diet as compared with ERAS alone, without increasing overall complications or the readmissions rate.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Miralpeix, E., et al. (2019). "Role and impact of multimodal prehabilitation for gynecologic oncology patients in an Enhanced Recovery after Surgery (ERAS) program." International Journal of Gynecological Cancer 29(8): 1235-1243.
	Patients undergoing major surgery are predisposed to a decrease in functional capacity as a response to surgical stress that can delay post-operative recovery. A prehabilitation program consists of patient preparation strategies before surgery, and include pre-operative measures to improve functional capacity and enhance post-operative recovery. Multimodal prehabilitation may include exercise, nutritional counseling, psychological support, and optimization of underlying medical conditions, as well as cessation of unfavorable health behaviors such as smoking and drinking. Currently, there are no standardized guidelines for prehabilitation, and the existent studies are heterogeneous; however, multimodal approaches are likely to have a greater impact on functional outcomes than single management programs. We have reviewed the literature on prehabilitation in general, and in gynecologic surgery in particular, to identify tools to establish an optimal prehabilitation program within an Enhanced Recovery After Surgery (ERAS) protocol for gynecologic oncology patients. We suggest a safe, reproducible, functional, and easy-to-apply multimodal prehabilitation program for gynecologic oncology practice based on patient-tailored pre-operative medical optimization, physical training, nutritional counseling, and psychological support. The analysis of the prehabilitation program implementation in an ERAS protocol should undergo further research in order to test the efficacy on surgical outcome and recovery after surgery.Copyright © IGCS and ESGO 2019.

Miranda, M., et al. (2021). "Vaginal lactoferrin in prevention of preterm birth in women with bacterial vaginosis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 34(22): 3704-3708.
	OBJECTIVE: To evaluate use of vaginal lactoferrin in prevention of preterm birth (PTB) in women with first trimester bacterial vaginosis and prior spontaneous PTB. METHODS: This is a retrospective cohort study of all consecutive singleton gestations with prior PTB, and first trimester diagnosis of bacterial vaginosis. Women who were found to have bacterial vaginosis were recommended lactoferrin 300 mg vaginal tablets daily for 21 days. The primary outcome was the incidence of PTB at less than 37 weeks of gestations. Outcomes were compared in women who received daily lactoferrin with those who did not. RESULTS: During the study period, 847 pregnant women with prior spontaneous PTB were screened for bacterial vaginosis. Of them, 193 were found to have bacterial vaginosis in the first trimester, with an overall incidence of 22.8%. Out of the 193 women, 125 met the inclusion criteria for the study and were analyzed. Sixty of the included women received vaginal lactoferrin, while 65 did not. Women who received supplementation with lactoferrin had a significantly lower rate of PTB < 37 weeks (25.0 versus 44.6%; p = .02), lower mean gestational age at delivery (37.7 ± 3.2 versus 35.9 ± 4.1 weeks; p = .01), and lower rate of admission for threatened PTL (45.0 versus 70.8%; p = .04). No between-group differences were noticed in the other outcomes, including chorioamnionitis, PPROM < 34 weeks, and neonatal outcomes. No cases of late miscarriage were reported in our cohort. No cases of adverse events were reported. CONCLUSION: Based on this small single-center retrospective study, supplementation with vaginal lactoferrin in women with first trimester bacterial vaginosis may be an option to reduce the risk of preterm delivery.

Miremberg, H., et al. (2022). "Exposure to an informative video before planned Cesarean-delivery and maternal anxiety-a multicenter randomized controlled trial." American Journal of Obstetrics and Gynecology 226(1): S87‐S88.
	Objective: We aimed to study the impact of exposure to a detailed informative video on maternal anxiety levels, childbirth experience, and patient satisfaction – in patients undergoing a primary Cesarean delivery (CD). Study Design: We performed a multicenter randomized control trial. Patients planned to undergo a scheduled primary CD were recruited. All patients in the intervention group were exposed to an informative video upon recruitment. This 6‐minute video described in detail the expected CD process: preparations before entering the operation room, regional anesthesia administration, sterile covering, the surgical procedure itself, and recovery (including mobilization and lactation). Situation‐specific anxiety was measured at recruitment, before exposure to the video (S1), at the day of operation (S2) and at postpartum day 1 (S3) using the State‐Trait Anxiety Inventory (STAI‐Y) score. Additionally, patients answered 11‐ item Childbirth experience questionnaire (CEQ). A sample size of 63 per group was planned to achieve 80% power to detect a difference of 5 points in the primary outcome ( STAI‐Y score at the day of operation). Results: Overall, 157 patients from 4 medical centers in Israel were randomized and 132 patients were analyzed after completing all questionnaires, 64 patients in the video group and 68 patients in the control group. The groups did not differ in demographics and delivery characteristics as well as similar baseline anxiety levels (S1). On operation day (S2, the primary outcome), significantly lower anxiety levels were reported in the video group compared to control group (STAI‐Y scores 41.3±9.5 vs. 49.3±10.3, p<0.001). Moreover, anxiety levels in postpartum day 1 (S3) remained significantly lower in the video group (p < 0.001). No differences between the groups in CEQ score or patient satisfaction were demonstrated. Conclusion: A detailed informative video prior to primary CD decreased maternal anxiety before and after the procedure. [Formula presented] [Formula presented]

Miremberg, H., et al. (2022). "An informative video before planned cesarean delivery and maternal anxiety-a multicenter randomized controlled trial." American Journal of Obstetrics & Gynecology MFM 4(3): 100604.
	BACKGROUND: Cesarean delivery is one of the most common procedures performed in obstetrics, and although cesarean delivery is a blissful occasion, it is commonly associated with fear and anxiety for the new mother. OBJECTIVE: We aimed to study the impact of watching a detailed, informative video on maternal anxiety levels, childbirth experience, and patient satisfaction in patients undergoing a primary cesarean delivery. STUDY DESIGN: We performed a multicenter randomized control trial. Women scheduled to undergo a primary nonemergent cesarean delivery were recruited. All participants in the intervention group watched an informative video on recruitment. This 4‐minute video described in detail the expected cesarean delivery process: preparations before entering the operation room, regional anesthesia administration, sterile covering, the surgical procedure itself, and recovery (including mobilization and lactation). Situation‐specific anxiety was measured at recruitment, before exposure to the video (S1), at the day of the operation (S2), and at postpartum day 1 (S3) using the State‐Trait Anxiety Inventory score. In addition, participants answered a 10‐item Childbirth Experience Questionnaire. A sample size of 63 per group was planned to achieve 80% power to detect a difference of 5 points in the primary outcome (State‐Trait Anxiety Inventory score on the day of the operation). RESULTS: Overall, 154 participants from 4 medical centers were randomized, and 132 participants were analyzed after completing all questionnaires, 64 participants in the video group and 68 participants in the control group. The groups did not differ in demographics and delivery characteristics and had similar baseline anxiety levels (S1). On operation day (S2, the primary outcome), significantly lower anxiety levels were reported in the video group than in the control group (State‐Trait Anxiety Inventory scores, 41.3±9.5 vs 49.3±10.3; P<.001). Moreover, anxiety levels in postpartum day 1 (S3) remained significantly lower in the video group (P<.001). No difference between the groups in childbirth experience score or patient satisfaction was demonstrated. CONCLUSION: A detailed informative video shown to patients before primary cesarean delivery decreased maternal anxiety levels before and after the procedure.

Mirhosseini, S., et al. (2021). "Effect of aromatherapy massage by orange essential oil on post-cesarean anxiety: a randomized clinical trial." Journal of complementary & integrative medicine 18(3): 579-583.
	OBJECTIVES: Many women in recent years have been willing to undergo puncture surgery for childbirth, which, like other surgeries, has physical and psychological side effects such as incision, infertility, chronic pain, and anxiety. Therefore, it is important to reduce and improve these side effects. The aim of this study was to determine the effect of foot massage with orange essential oil on anxiety in women undergoing cesarean section. METHODS: This randomized clinical trial study was conducted in 2019 on 80 women referred to Bahar Shahroud Hospital after cesarean section surgery. The samples were divided into two groups by intervention (foot massage with orange essential oil) and control (foot massage without orange essential oil). The Spielberger scale was used to determine anxiety scores after cesarean section. In the intervention group, the feet were massaged with orange essential oil, and in the control group, the orange essential oil massage was performed without oil. Anxiety before, immediately after, and 60 min after the intervention was measured and evaluated in both groups. Data analysis was performed using descriptive and inferential statistics. Significant levels were considered for all statistical tests (p<0.05). RESULTS: The anxiety score before the intervention in the two groups of intervention and control was 57.12 ± 3.12 and 57.07 ± 3.54, respectively, which were not significantly different, but immediately after the intervention, the anxiety scores in both groups decreased significantly so that there was a further decrease in the intervention group (52.10 ± 4.75 and 56.02 ± 3.77), 1 h after the intervention, the anxiety score in the intervention group decreased compared to the previous stage and increased in the control group (50.40 ± 3.74 and 56.85 ± 4.27). CONCLUSIONS: Foot massage with orange essential oil can probably be effective as a proper nursing intervention in reducing anxiety after cesarean section surgery.

Miri, S. R., et al. (2022). "A Systematic Review on Overall Survival and Disease-Free Survival Following Total Pelvic Exenteration." Asian Pacific journal of cancer prevention : APJCP 23(4): 1137-1145.
	BACKGROUNDS: Total Pelvic Exenteration (TPE) is a radical operation for malignancies in which all of the organs inside the pelvic cavity, including the female reproductive organs, the lower urinary tract, and a part of the rectosigmoid are removed. In this study, we aimed to conduct a systematic review to assess the overall survival (OS) and disease-free survival (DFS) following TPE. METHODS: This systematic review is composed of a comprehensive review of PubMed and Scopus databases with various related keywords to synthesis the overall survival and disease-free survival following TPE. The Synthesis Without Meta-analysis guideline was used to summarize the results. RESULTS: We included the results of 39 primary studies and the results revealed that one-year OS of gynecological cancer in patients who have undergone TPE ranged from 50.0% to 72.0% and the 5-years OS ranged from 6.0% to 64.6%. The one-year survival rate of colorectal cancer patients was reported to be over 80% in almost all studies. The 3-year survival rate of patients varied from 25% to 75% and the lowest 5-year survival rate was 8% and the highest survival rate was 92%. To synthesis the disease-free survival rate in colorectal cancer, ten studies were included and one-year recurrence rate was 9.1% and the one-year DFS was reported as 61.0%. Three-year recurrence rate study was 20.4% and 3 and 5-year DFS ranged from 22.0% to 78.0%. CONCLUSIONS: The results suggested that DFS in primary advanced cancers is higher than locally recurrence tumors. This review showed that patient overall survival and disease-free survival rates have increased over time, especially at high volume centers that are more experienced and possibly better equipped. Therefore, it can be suggested that the attitude towards PE as a palliative surgery can be turned into curative surgery.

Miriello, D., et al. (2022). "Management of women with uterine fibroids in reproductive center: retrospective analysis of clinical and reproductive outcomes." Minerva Obstetrics and Gynecology 74(2): 130-136.
	Background: Uterine fibroids are the most common benign tumor in women. According to literature, submucosal myomas have a negative effect on reproductive outcomes in women undergoing assisted reproductive techniques (ART) but there are fewer data concerning intramural fibroids. During last years, ulipristal acetate (UPA) 5 mg was widely used as medical option of fibroid's treatment, but from 2020, the Pharmacovigilance Risk Assessment Committee (PRAC) has revoked the marketing authorization after some cases of liver toxicity.; Methods: In this observational, retrospective study we collected data from a sample of 23 women affected by symptomatic uterine fibroids (from type 1 to type 7 according FIGO classification) followed in our center for assisted reproduction from 2016-2019. All patients received 5 mg/day UPA for three months, followed by two months of wash-out therapy. A group of 13 women treated with UPA, with intramural fibroid not distorting the uterine cavity, after wash-out therapy, affected by tubal or idiopathic factors of infertility too, underwent ART. We also evaluated a control group of women, not affected by fibroids, randomly selected from a general group of our ART patients, similar by age, BMI, and cause of infertility only idiopathic or tubal factors. We evaluated the impact of UPA on reduction of fibroid volume, symptomatology and distortion of the cavity in all the women treated, and the IVF (in-vitro fertilization) outcome between the fibroid group of women affected by intramural fibroids who underwent ART, and the control group.; Results: In all the women treated with UPA the overall median fibroid volume pretreatment was 45.168±35.360 mm 3 , that decreased to a mean value of 22.592±22.116 mm3 post one cycle of UPA, with an overall mean decrease of -22.586 mm 3 (of 49%) statistically significant (P=0.00001). After treatment, the distortion of the uterine cavity reduced in high percentage of cases: 85,71% (type 1-2), χ 2 difference in respect to the value pretreatment of 0.3941, and 86.96% of patients subjectively referred an improvement in the symptomatology. In the group of 13 women that undergone ART, after one IVF cycle for each patient, we obtained 61% of positivity of dosage of beta human chorionic gonadotropin (hCG) after UPA treatment, and we obtained a similar value in the control group.; Conclusions: In our little sample we have observed that UPA represented a valid non-invasive medical treatment strategy for fibroids in women candidate for (IVF, not only in women affected by sub-mucosal, but also by intramural fibroids not distorting uterine cavity. After a single, three months course of treatment, we obtained good results in terms of reduction of fibroid's volume and improvement of symptomatology, without side effects, preparing a more favorable environment for ART.

Miriyala, R., et al. (2022). "Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(3): 260-265.
	Background: Cisplatin-based concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. In view of the difficulties associated with implementation of standard radiation protocols in low- and middle-income countries and the associated toxicities of chemoradiation, neoadjuvant chemotherapy followed by surgery has been tried as an alternative treatment for locally advanced cervical cancer.; Methods: A comprehensive review was undertaken of the existing literature, caveats and potential avenues of neoadjuvant chemotherapy followed by surgery compared with chemoradiation in locally advanced cervical cancer.; Results: Randomized studies conducted in the pre-chemoradiation era comparing neoadjuvant chemotherapy followed by surgery with definitive radiotherapy alone showed favorable outcomes with the chemo-surgical approach. However, contemporary studies evaluating the role of neoadjuvant chemotherapy followed by surgery have failed to establish this approach as the standard. About 25-30% of patients who undergo neoadjuvant chemotherapy remain inoperable and require definitive chemoradiation. A similar proportion of patients would require adjuvant (chemo)radiation after neoadjuvant chemotherapy followed by surgery, resulting in excessive morbidity. Evaluation of time trends across the past few decades reveals that the advancements in delivery of radiation (external beam and brachytherapy) have translated into improvement in outcomes for locally advanced cervical cancer, while a similar trend was not observed for surgery or chemotherapy.; Conclusion: Neoadjuvant chemotherapy followed by surgery cannot be considered a standard of care in patients with locally advanced cervical cancer. This approach needs further clinical research to generate robust high-quality evidence especially for the sub-sets that might potentially benefit in terms of survival, toxicity and quality of life, against the gold standard treatment of concomitant chemoradiation.; Competing Interests: Competing interests: UM: serves on DSMB/Advisory board of AstraZeneca and is Secretary of the Indian Brachytherapy Society. SG: serves on DSMB/Advisory board of Pfizer, AstraZeneca, Novartis, Eisai and Eli Lily and is Vice-President of the Indian Society of Medical and Pediatric Oncology and General Secretary of the Women’s Cancer Initiative-Tata Memorial Hospital. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Mirza, M. (2022). "ENGOT-EN19/NSGO-CTU/ALPACA: A RANDOMISED PHASE II TRIAL OF ALPELISIB IN COMBINATION WITH LETROZOLE FOR PATIENTS WITH ADVANCED OR RECURRENT ENDOMETRIAL CANCER." International Journal of Gynecological Cancer 32(Supplement 3): A229.
	Objectives Patients with advanced or recurrent EC have few treatment options and succumb to the cancer rapidly. Approximately 40% of patients with ER-positive, endometrial cancer have activating mutations in the gene PIK3CA, inducing hyperactivation of the alpha isoform of phosphatidylinositol 3- kinase (PI3K). Endocrine therapy is the standard treatment for patients with ER-positive advanced endometrial cancer. However, acquired resistance to endocrine-based therapy remains a challenge. Targeted therapies, such as PI3K inhibitors, have been developed to overcome resistance to existing therapies This prospective, multicenter, open-label, randomized phase II study is evaluating the activity of alpelisib, a PIK3CA inhibitor in combination with letrozole in relapsed endometrial cancer. Methods Patients with PIK3CA mutated, G1-2 endometriod adenocarcinoma relapsed after first-line systemic therapy are eligible. Patients must have measurable disease and ECOG performance status 0-1. Patients are randomized into one of the two treatment arms, (A:B), in a 1:1 randomization (n=86): Arm A (letrozole): Arm B (letrozole plus alpelicib. Primary endpoint is investigator assessed progression-free survival. Study sponsor is the Nordic Society of Gynaecological Oncology - Clinical Trial Unit and is being conducted in six cooperative groups (MaNGO, BGOG, DGOG, PMHC, NOGGO & NSGO). Results Study is expected to start enrolment in Q4 2022 Conclusions The positive outcome will further improve the outcome of our patients and phase III validation trial will follow.

Mirza, M., et al. (2021). "A randomised phase ii study of combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer. fandango/engot-en1/fandango." International Journal of Gynecological Cancer 31(SUPPL 1): A371‐372.
	Introduction/Background Endometrial cancer (EC) patients (Pts) with advanced and recurrent disease relapse despite treatment with combination chemotherapy and have a short progression‐ free survival (PFS). Nintedanib (N) is a potent, orally available triple receptor tyrosine kinase inhibitor targeting VEGFR 1‐3, PDGFR α/β, and FGFR 1‐3. This study explored the preliminary efficacy of nintedanib in EC. Methodology The primary objective of this placebo‐controlled, randomized study was to evaluate efficacy defined by median PFS of concomitant and maintenance N against placebo (P) in combination with chemotherapy. Patients with histologically confirmed stage IIIC2 or IVA & B or relapsed after adjuvant therapy for stage I‐III disease; prior surgery; adjuvant chemotherapy; radiation therapy; hormonal therapy in metastatic setting; with measurable/non‐measurable disease were permitted. Pts were randomized 1:1 to receive N 200mg or P, twice daily days 2‐21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175mg/m2) every 21 days) and continuously in maintenance phase. N/P was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification by stage of disease, prior adjuvant chemotherapy and measurable/non‐measurable disease. This is an ENGOT Model A study. Clinical trial information: NCT02730416. Result(s) 146 of 148 pts were eligible for PFS: 72N/74P; mean age 66yrs; FIGO stage III 18%, IV 42%, recurrent 40%; follow‐up 30 mo. N added to chemotherapy did not improve PFS (119 events) as compared to chemotherapy plus P: median for N 8.3 vs. for P 7.2 mo; hazard ratio (HR) adjusted for stratification factors 1.03; 95% confidence interval (CI),[0.71 to 1.48]; p0.879. Median overall survival (85 events) for N 20 vs. for P 22 mo; HR: 1.10; CI: 0.72‐1.69; p0.665. Treatment‐emerged grade 3‐4 adverse events were higher in N vs P arm: liver function tests 13%/0%; diarrhea 12%/6%; neutropenia 21%/14%; asthenia 4%/1%. Patient-reported outcomes will be reported. Conclusion Addition of nintedanib to chemotherapy did not improve PFS nor OS. This regimen cannot be recommended to undergo further testing in a phase III trial.

Mirza, M., et al. (2023). "Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: a placebo-controlled randomized phase 3 trial (ENGOT-EN6-NSGO/GOG-3031/RUBY) (LBA 11)." Gynecologic Oncology 176(Supplement 1): S43-S44.
	Objectives: Carboplatin-paclitaxel (CP) is the standard of care (SOC) for first-line treatment of primary advanced or recurrent endometrial cancer (EC), yet median overall survival (OS) is. Method(s): RUBY is a phase III, global, randomized, double-blind, multicenter, placebo (PBO)-controlled study. Eligible pts. had first recurrent or primary advanced stage III or IV EC. Stratification factors were MMR/microsatellite stability status, prior external pelvic radiotherapy, and disease status. Pts were randomized 1:1 to receive dostarlimab 500 mg, or PBO, plus carboplatin AUC 5 and paclitaxel 175 mg/m2 q3w for 6 cycles, followed by dostarlimab 1000 mg, or PBO, monotherapy q6w for up to 3 years. Primary endpoints were progression-free survival (PFS) by investigator assessment per RECIST version 1.1 and OS. The graphical method was used for hypothesis testing of PFS in the dMMR/MSI-H population, then the overall population, and OS in the overall population. In addition, a prespecified exploratory analysis of PFS in the MMR proficient (MMRp)/microsatellite stable (MSS) population was performed. Safety was also assessed. Result(s): Of 494 pts. randomized (245 dostarlimab+CP; 249 PBO + CP), 23.9% had dMMR/MSI-H tumors (53 dostarlimab+CP; 65 PBO + CP), 47.8% had recurrent disease; 18.6% and 33.6% had primary stage III and IV disease, respectively. PFS was significantly longer in the dostarlimab+CP arm than the PBO + CP arm among the dMMR/MSI-H (HR: 0.28, 95% CI: 0.162-0.495; P < 0.0001) and overall populations (HR: 0.64, 95% CI: 0.507-0.800; P < 0.0001; Table). OS data were not mature but had a favorable trend in all populations. The most common treatment-emergent adverse events (TEAEs) in both arms were nausea, alopecia, and fatigue. Discontinuation of dostarlimab or PBO due to a TEAE occurred in 17.4% of pts. receiving dostarlimab+CP and 9.3% of pts. receiving PBO + CP, respectively. The safety profile of dostarlimab+CP was generally consistent with the safety profiles of the individual components. Conclusion(s): Dostarlimab+CP showed statistically significant and clinically meaningful PFS benefits in the dMMR/MSI-H and overall populations compared with CP alone. Clinically relevant benefit in PFS was also observed in the MMRp/MSS population. An early trend toward improved OS was observed in all populations. The combination of dostarlimab+CP represents a new SOC for pts. with newly diagnosed primary advanced or recurrent EC. [Formula presented]Copyright © 2023

Mirza Mansoor, R., et al. (2023). "Prospective evaluation of the tolerability and efficacy of niraparib dosing based on baseline body weight and platelet count: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial." Cancer 129(12): 1846-1855.
	Background: The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.; Methods: In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily in all other patients. Efficacy and safety outcomes were assessed by starting dose.; Results: Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46-0.76] vs. ISD HR, 0.69 [95% CI, 0.48-0.98]) and the homologous recombination-deficient (FSD HR, 0.44 [95% CI, 0.30-0.64] vs. ISD HR, 0.39 [95% CI, 0.22-0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD.; Conclusions: In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen. (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Mirza, M. R., et al. (2022). "A RANDOMISED CLINICAL TRIAL INVESTIGATING OLAPARIB, DURVALUMAB AND AN ANTICANCER VACCINE, UV1 AS MAINTENANCE THERAPY IN PATIENTS WITH RECURRENT OVARIAN CANCER. ENGOT-OV56-NSGO-CTU-DOVACC." International Journal of Gynecological Cancer 32(Supplement 2): A315.
	Introduction/Background Outcome of ovarian cancer patients has considerably improved by introduction of maintenance PARP inhibitors; however, most patients subsequently relapse and there is a need for further improvement. Combinations of targeted therapy and immunotherapy are of interest due to their single agent efficacy in different stages of ovarian cancer. To further enhance the response rate, one approach may be to integrate an anticancer vaccine aiming to activate an immune response against tumour-related antigens into a regime of combined targeted therapy and immunotherapy. This prospective, multicenter, open-label, randomized phase II maintenance study is evaluating the efficacy of UV1-olaparibdurvalumab combination as maintenance therapy after platinum combination therapy for BRCAwt patients with relapsed ovarian cancer. Methodology Patients with BRCAwt epithelial ovarian cancer, relapsed >6 months after last chemotherapy (maximum 4 prior lines of chemotherapy), in response to last chemotherapy, ECOG performance status 0-1 are eligible. Patients are randomized into one of the three treatment arms, (A:B:C), in a 1:1:2 randomization (n=184):Arm A (olaparib): 46 subjectsArm B (olaparib plus durvalumab): 46 subjectsArm C (olaparib plus durvalumab plus UV1): 92 subjectsPatients are stratified according to:HRD statusPrevious use of PARP inhibitor. Primary objective is to compare the preliminary efficacy of maintenance treatment with olaparib (arm A) to that of olaparib plus durvalumab and UV1 (arm C). Study sponsor is the Nordic Society of Gynaecological Oncology - Clinical Trial Unit and is being conducted in six ENGOT cooperative groups (AGO-A, BGOG, DGOG, HeGOG, NOGGO).(NCT04742075) Results Expected results Study is enrolling patients in 11 ENGOT countries Conclusion The positive outcome will further improve the outcome of our patients.

Mirza, M. R., et al. (2022). "UP-NEXT (ENGOT-OV71-NSGO-CTU/GOG- 3049): A STUDY OF UPITIFAMAB RILSODOTIN (UPRI), A NAPI2B-DIRECTED ANTIBODY DRUG CONJUGATE (ADC) INPLATINUM-SENSITIVE RECURRENT OVARIAN CANCER." International Journal of Gynecological Cancer 32(Supplement 2): A234.
	Introduction/Background UpRi is a first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous ovarian cancer (HGSOC) with limited expression in healthy tissues. It's estimated that about two-thirds of HGSOC patients are NaPi2bhigh. Studies are being conducted to evaluate UpRi safety and efficacy in platinum-resistant ovarian cancer (PROC), but there remains an unmet need in the maintenance setting for patients with platinum-sensitive, recurrent ovarian cancer (PSOC), particularly in patients who received standard of care treatment (platinum-based chemotherapy) and are at high-risk of early relapse. Methodology UP-NEXT is a Ph3 study evaluating UpRi monotherapy as post-platinum maintenance therapy in recurrent PSOC, enrolling patients with NaPi2b-high tumors (defined as TPS >=75). Patients must have received 2-4 prior lines of platinum containing chemotherapy, achieved a partial or complete response in their penultimate platinum regimen, and progressed >6 mo after completion of the last dose of platinum. Patients may be enrolled if their best response to the last line of treatment is no evidence of disease, complete or partial response, or stable disease. If patients have a known BRCA mutation, prior PARPi treatment is required. Patients who received bevacizumab in combination with their last platinum containing regimen are excluded. Patients are randomized 2:1 to UpRi or placebo, given IV Q4W. The primary endpoint is PFS assessed by BICR, with key secondary endpoint of OS. UP-NEXT is conducted in collaboration with ENGOT(Ov71- NSGO-CTU) and GOG(3049). ~350 patients will be enrolled globally. NCT05329545 Results N/A - trial in progress Conclusion N/A - trial in progress.

Mirzaee, F., et al. (2021). "Comparing the effect of acupressure with or without ice in LI-4 point on labour pain and anxiety levels during labour: a randomised controlled trial." Journal of Obstetrics and Gynaecology 41(3): 395‐400.
	The aim of this study was to assess the effect of acupressure with or without ice on reducing pain and anxiety during labour. The anxiety level of mothers was measured before and after study using Spielberger Inventory along with the labour pain. To improve the strength of this study, a meta‐analysis was conducted on the effect of acupressure in point LI‐4 on anxiety during labour. Ninety women in labour were randomly divided into three groups: acupressure with ice, acupressure without ice and the control group. The result suggested that women receiving both acupressure with ice (p =.005) or without ice (p <.001) experienced less labour pain in comparison with the control group. Also, the labour pain severity in acupressure without ice was lower than the group with ice (p <.001). Acupressure with (p = 1) or without (p =.09) ice was not significantly different from the control group in terms of the anxiety level. However, women in the group of acupressure without ice experienced less anxiety in comparison with acupressure with ice (p =.04). The difference in pain severity before and after treatment with acupressure with (RCI = 2.86) or without ice (RCI = 5.54) was clinically significant. The intervention was not clinically meaningful in terms of anxiety.Impact statementWhat is already known on this subject? Previous trials have exhibited that acupressure with/without ice reduced pain and anxiety during labour. What do the results of this subject add? The results of this research was consistent with previous studies, suggesting that acupressure, with or without ice, is more effective than the control group regarding labour pain. However, the group of acupressure with ice was not different from the control group with respect to the anxiety level. What are the implications of these findings for clinical practice and/or further research? In light of advantages, such as growing preference of women, researcher and health care providers for physiological delivery coupled with its safety and simplicity, it can be used as an effective technique to manage labour pain. Further studies are required to assess the effect of acupressure at L4 on the anxiety level.

Mirzaee, F., et al. (2021). "The effect and safety of Berberine on polycystic ovary syndrome: a systematic review." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 41(5): 684-689.
	The aim of this systematic review is to assess the effect of Berberine (BBR) on women's health to provide greater insights about its effect on women with polycystic syndrome for both patients and health care providers. Electronic databases such as PubMed, Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from the base to July 1th, 2019 to identify clinical trials and randomised controlled trials that had explored the effect of BBR on the polycystic syndrome. With regard to the weight and composition body, BBR did not have any significant effect on reducing body weight and conflicting findings had been reported about waist circumference (WC) and body mass index (BMI). However, BBR led to a significant decrease in waist to hip ratio (WHR), profile hormonal insulin resistance (IR), and insulin resistance (HOMA-IR). Further, androstenedione dropped significantly following treatment with BBB. However, BBB did not have a significant effect on follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Mirzaei, M., et al. (2023). "The effects of hydroxychloroquine on pregnancy outcomes in infertile women: a systematic review and meta-analysis." Journal of medicine and life 16(2): 189-194.
	A promising strategy for controlling repeated implantation failure (RIF) may be the use of hydroxychloroquine (HCQ). To the best of our knowledge, no systematic review has been conducted on the effects of hydroxychloroquine on pregnancy outcomes. A systematic research of the following electronic databases was conducted: Cochrane, EMBASE-Ovid, PubMed, Web of Science, and Scopus from inception to December 2021, using the following keywords [hydroxychloroquine] AND [infertility]. Fertilization and rate of live birth were significantly higher in the HCQ+ prednisone (PDN) group than in the PDN alone group. However, the abortion rate was not different between the two groups. The meta-analysis of two studies revealed no statistical significance between the PDN group and HCQ+PDN group regarding clinical pregnancy rate (OR=.14 [95%CI: 0.4-4.370]; heterogeneity; P=0.13; I2=54%; random effect model) and implantation rate (OR=1.99 [95%CI: 0.94-4.2]; heterogeneity; P=0.37; I2=0%; fixed-effect model). While HCQ may help improve fertilization and live birth rates, adding it to prednisone did not improve overall pregnancy outcomes. This systematic review should be used with caution due to the small size, study design, and difference in the studies' population.; Competing Interests: The authors declare no conflict of interest. (©2023 JOURNAL of MEDICINE and LIFE.)

Mirzaei, M., et al. (2021). "Evaluation of the Clinical Efficacy and Complications of Duloxetine in Comparison to Solifenacin in the Treatment of Overactive Bladder Disease in Women: a Randomized Clinical Trial." Urology Journal 18(5): 543‐548.
	PURPOSE: SNRIs (serotonin and norepinephrine reuptake inhibitors) like duloxetine are known to have role in the treatment of anxiety disorder and stress urinary incontinence. According to the correlation of anxiety disorder and overactive bladder, this study aimed to evaluate the clinical efficacy and complications of duloxetine (SNRI) as a medication in the treatment of overactive bladder in the female patients. We were interested to know the probable therapeutic effect and side effects of duloxetine in overactive bladder. METHODS AND MATERIALS: In this single‐blinded interventional randomized clinical trial, 60 female patients with idiopathic overactive bladder (hyperreflexia) referred to the urology clinic, were divided into two groups as pilots. The first group were treated by 10mg/daily solifenacin and the second group received 20mg/daily duloxetine. The patients were evaluated by the ICIQ‐OAB Questionnaire before and after one‐month follow‐up period. The intervention primary outcomes were evaluated by the patient's presentation of the frequency, nocturia, urgency, urge urinary incontinence and the drugs side effects as secondary outcomes were checked. Results: Sixty women with confirmed overactive bladder disease were evaluated. Solifenacin and duloxetine had the same effect on the treatment of overactive bladder (p value=0.148). The clinical symptoms were obviously relieved in both groups after treatment. Side effects were insignificantly more common in the solifenacin group (p value>0.05). However, the different frequency of blurred vision in the two groups was statistically significant (p value=0.04). The most common complication in solifenacin and duloxetine group was anxiety. CONCLUSION: The results showed that solifenacin and duloxetine improved overactive bladder symptoms. According to this evaluation, duloxetine can be a suitable alternative option for overactive bladder treatment, due to the acceptable therapeutic effect and side effects.

Mirzaei, N., et al. (2022). "A randomized trial assessing the efficacy of Silymarin on endometrioma-related manifestations." Scientific Reports 12(1): 17549.
	To study the effect of silymarin on the Interleukin-6 (IL-6) level, size of endometrioma lesion, pain, sexual function, and Quality of Life (QoL) in women diagnosed with endometriosis. This randomized, double-blind placebo-controlled clinical trial was performed on 70 women with endometriosis which was divided into two groups of intervention and control. The intervention was 140 mg silymarin (or matching placebo) administered twice daily for 12 weeks. The volume of endometrioma lesions, the level of IL-6 concentration in serum, pain, sexual function, and QoL were analyzed before and after the intervention. The means of endometrioma volume (P = 0.04), IL-6 (P = 0.002), and pain (P < 0.001) were reduced significantly in the silymarin group after intervention. However, the QoL and female sexual function did not improve substantially in the two groups (P > 0.05). Silymarin significantly reduced interleukin-6 levels, sizes of endometrioma lesions, and pain-related symptoms. The trial has been registered in the Iranian Registry of Clinical Trials (IRCT20150905023897N5) on 4th February 2020 (04/02/2020) ( https://en.irct.ir/trial/42215 ) and the date of initial participant enrollment was 2nd March 2020 (02/03/2020).

Mirzamoradi, M., et al. (2023). "Evaluation of the Effect of Low-dose Aspirin on the Prevention of Preterm Delivery in Women with a History of Spontaneous Preterm Delivery." Revista Brasileira de Ginecologia e Obstetricia 45(11): e646‐e653.
	OBJECTIVE: Currently, uteroplacental vascular disorders are considered one of the main mechanisms of spontaneous preterm delivery (PTD). Low‐dose aspirin is used to prevent pre‐eclampsia, which has a similar mechanism; hence, the present study aimed to investigate the effect of low‐dose aspirin on the prevention of PTD in women with a history of spontaneous PTD. METHODS: The present pilot randomized clinical trial was conducted on 54 pregnant women in the aspirin group (taking 80 mg daily until the 36th week and classic treatment) and 53 patients in the control group (only receiving classic treatment). RESULTS: Forty‐three patients (40%) presented before 37 weeks due to symptoms of PTL. Preterm delivery (< 37 weeks) occurred in 28 patients (26%), and there was no significant difference between the aspirin and control groups (10 patients [19%] and 18 patients [34%], respectively; p = 0.069). The time of preterm delivery was early (< 34 weeks) in 6 patients (21%), and its cause was spontaneous labor in 23 patients (82%) which was not significantly different between the two groups (p > 0.05). Out of 40 patients with spontaneous labor, 25 patients (63%) had a PTD, which was significantly lower in the aspirin group than in the control group (9 patients [45%] versus 16 patients [80%], respectively; p = 0.022). CONCLUSION: The findings of the present study demonstrated that despite the reduction in the incidence of PTD using low‐dose aspirin, the reduction rate was not statistically significant. On the other hand, in patients with spontaneous labor prone to PTD, aspirin was effective in reducing the incidence of PTD.

Misasi, G., et al. (2023). "Urodynamic assessment in patients suffering concomitant overactive bladder syndrome (OAB-S) and vulvo-vaginal atrophy (VVA) treated with ospemifene." Maturitas 173: 43.
	Introduction and Aim of the Study: Overactive Bladder Syndrome (OAB-S) is a complex and multifactorial syndrome in which menopausal transition and the ageing process could be contributing factors. Urinary Urgency (UU) is the key symptom reported in the condition of OAB in Post-Menopausal Women (PMW) suffering from Genitourinary Syndrome of Menopause. Even if there are some evidences that the use of hormonal treatments like vaginal estrogens in PMW may be helpful, the evidence on the possible role of others hormonal treatments in improving OAB-S in PMW is scant. Ospemifene is a Selective Estrogen Receptor Modulator (SERM) licensed for treatment of Vulvo-Vaginal Atrophy (VVA). The aim of the study is to evaluate the safety and effectiveness of Ospemifene in the treatment of concomitant OAB-S and VVA in PMW. Material(s) and Method(s): This is a prospective open-label intervention trial. Forty PMW suffering concomitant OAB and VVA were enrolled. All patients received oral Ospemifene 60 mg/die for 12-weeks. Objective data was accomplished by urodynamic evaluations and subjective data by 3-days bladder diary, International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI) and ICIQ-OAB. All data were assessed at baseline and after 12-weeks. Patients were monitored for discomfort and side-effects. The main outcome measure was to evaluate the impact of therapy on the quality of life (QoL) in relation to the OAB-S. Result(s): The median number of voids in 24h was found reduced from 10 (8-12) to 8 (8-9) (p<0.001), the UU incontinence episodes in 24h was reduced from 7 (5-8) to 5 (5-6.7) (p<0.001). The median number of nocturia events was found reduced from 3 (2-3.7) to 2 (2-3) (p<0.001). The median overall score of ICIQ-UI and ICIQ-OAB before and after treatment was found improved from 15 (14-15) to 12 (10.5-13.5) (p<0.001) and from 11.0 (9.0-12.0) to 8.0 (6.0-9.5) respectively. The urodynamic data displayed a statically significant improvement after treatment during bladder filling, in terms of First Voiding Desire, Normal Voiding Desire, and Strong Voiding Desire. No differences were found in terms of flow parameters, bladder compliance, detrusor overactivity and urethral closure parameters. Conclusion(s): Our preliminary data suggest that treatment with Ospemifene in PMW suffering from OAB-S is associated with a reduction of the urgency events and an overall improvement on QoL, consistent with the effect of SERM on urogenital atrophy.Copyright © 2023

Mishra, D. G., et al. (2022). "Comparison of Effectiveness of Home-Based Verses Supervised Pelvic Floor Muscle Exercise in Women with Urinary Incontinence." Journal of mid-life health 13(1): 74-79.
	BACKGROUND: Urinary incontinence (UI) is a significant health problem with serious physical, psychological, and social consequences. Pelvic floor muscle exercise (PFME) is proven efficacious in the prevention and management of UI. A lack of trained physiotherapist in rural areas mars the uptake of physiotherapy and therefore innovative mechanisms are required. The present study was undertaken to evaluate the usefulness of home-based physiotherapy in the management of UI. MATERIALS AND METHODS: A total of 49 women, who screened positive for UI from a larger study conducted in 4 randomly selected villages of Charutar region, were included in the study. They were assigned home-based or supervised regimens randomly. All participants received education about UI and its management. A structured PFME schedule was developed. Participants in the supervised group received PFME by a trained physiotherapist, while those in the home-based group received training on exercise. Details of each session were documented through a daily diary in both groups. Revised urinary incontinence scale (RUIS) and incontinence impact questionnaire (IIQ-7) were administered at baseline and after 6 months to assess and compare the impact across groups. RESULTS: Analysis of variance (with post hoc comparisons) was employed to compare the effect of physiotherapy across groups. Only 18 (10 supervised and 8 home-based group) out of 49 women participated. Another 10 provided the required data, albeit had not done any exercises. The mean standard deviation of RUIS (P = 0.84) and IIQ-7 (P = 0.55) scores was similar at baseline across the groups. The RUIS (P = 0.01) and IIQ-7 (P = 0.006) improved significantly; however, post hoc analysis revealed that both RUIS and IIQ-7 improved significantly only in the supervised group. CONCLUSION: Supervised exercise worked better, whereas home-based exercise failed to achieve the desired impact. Identifying barriers in home-based exercise and finding feasible solutions would prove a breakthrough in the management of UI in resource-limited settings.

Mishra, N., et al. (2022). "Study on the Effect of Berberine, Myoinositol, and Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomised Study." Cureus 14(1): e21781.
	Objective: This study was conducted to see the effects of berberine, metformin, and myoinositol in women with polycystic ovary syndrome (PCOS).; Materials and Methods: Subjects were randomly assigned via computer-generated randomization to one of the three treatment groups. Group 1 received berberine hydrochloride 500 mg twice daily, group 2 received metformin hydrochloride 500 mg twice daily, and group 3 received myoinositol 1000 mg twice daily to compare clinically (mean weight, waist circumference, waist-to-hip ratio, and body mass index), metabolic (fasting blood sugar, serum fasting insulin, fasting blood sugar/serum fasting insulin [FBS/FI]), hormonal effects (serum total testosterone [TT], serum sex hormone-binding globulin [SHBG] and free androgen index) together with the lipid profile (total cholesterol, serum triglyceride, serum low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL], serum high-density lipoprotein [HDL]) in patients receiving metformin, berberine, and myoinositol before and after three months of treatment.; Results: Weight, BMI, waist circumference, waist-hip ratio, FBS, FI and fasting glucose/insulin ratio, total testosterone, free androgen index (FAI), SHBG, total cholesterol, triglycerides, LDL, VLDL, and HDL showed significant differences in three groups after three months of treatment (p<0.0001). Between the three groups, berberine showed greater differences in clinical, hormonal, and lipid parameters compared to metformin and myoinositol, while myoinositol showed greater improvement in carbohydrate metabolic parameters.; Conclusions: Metformin, the classical drug used in PCOS, improves all the parameters in polycystic ovary syndrome women. Berberine may have greater potential to reduce the risk of cardiovascular disease than metformin in PCOS patients due to its effect on body composition, lipid profile, and improvement in hormone status. Myoinositol administration improves endocrine parameters and insulin sensitivity. It may be considered as a first-line option in PCOS patients with insulin resistance without prediabetes or diabetes.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Mishra et al.)

Mishra, T., et al. (2023). "To Compare the Effect of Dexamethasone and Dexmedetomidine Given as Adjuvant with Ropivacaine in Transverse Abdominis Plane Block in Total Abdominal Hysterectomy." International Journal of Pharmaceutical and Clinical Research 15(3): 331‐336.
	Background: Several adjuvants have been used to improve the efficacy of the transversus abdominis plane (TAP) block because it has been used as an effective component of multimodal analgesic treatment for major abdominal surgeries. Dexmedetomidine and dexamethasone are two important additive when given as premixed with ropivacaine in transverse abdominis plane block, in terms of analgesic drug requirement and duration of postoperative analgesia in total abdominal hysterectomy patients. Aims and Objectives: To compare the analgesic effect of 0.2% ropivacaine as an adjuvant with dexamethasone 4mg and dexmedetomidine 10 mcg in transverse abdominis plane block for post‐operative analgesia in total abdominal hysterectomy. Materials and Methods: This study was conducted on 120 adult patients randomly allocated into two groups of 60 patients each. In Group A, the patient received 20 ml of 0.2% of ropivacaine with dexamethasone 4mg on either side, while in Group B, the patient received 20 ml of 0.2% of ropivacaine with dexmedetomidine10mcg on either side. Statistical analysis was done using appropriate parametric /non‐parametric tests and chi‐square tests. Results: The duration of post‐operative analgesia was significantly longer in Group B than in Group A (174.30 ± 24.24 minutes and 273.57 ± 13.25 minutes, respectively) (p<0.05). The total mean dose of post‐operative analgesia was lower in Group A (1.3± 0.5) than in Group B (2.3 ± 0.5). Numerical rating scale was lower in Group A at 2, 4, 8, 12 and 24 hours compared to Group B (p<0.05). Conclusion: Using dexamethasone as an adjuvant to ropivacaine improves the efficacy of TAP block in terms of duration and requirement of analgesia than dexmedetomidine with a significant reduction of post‐operative analgesic requirement without any adverse effects.

Mistry, M., et al. (2022). "Cannabidiol for the Management of Endometriosis and Chronic Pelvic Pain." Journal of Minimally Invasive Gynecology 29(2): 169-176.
	Objective: To review the available literature on the effect of cannabis-based products on the female reproductive system and establish whether there is any evidence that they benefit or harm patients with endometriosis and, therefore, whether there is sufficient evidence to recommend them.; Data Sources: An electronic-based search was performed in PubMed, Embase, and the Cochrane Database. Reference lists of articles retrieved were reviewed, and a gray literature search was also performed.; Methods of Study Selection: The original database search yielded 264 articles from PubMed, Embase, and the Cochrane Database, of which 41 were included. One hundred sixty-one studies relating to gynecologic malignancy, conditions unrelated to endometriosis, or therapies unrelated to cannabis-based products were excluded. Twelve articles were included from a gray literature search and review of references.; Tabulation, Integration, and Results: Most available evidence is from laboratory studies aiming to simulate the effects of cannabis-based products on preclinical endometriosis models. Some show evidence of benefit with cannabis-based products. However, results are conflicting, and the impact in humans cannot necessarily be extrapolated from these data. Few studies exist looking at the effect of cannabis or its derived products in women with endometriosis; the majority are in the form of surveys and are affected by bias. National guidance was also reviewed: at present, this dictates that cannabis-based products can only be prescribed for conditions in which there is clear published evidence of benefit and only when all other treatment options have been exhausted.; Conclusion: Current treatment options for endometriosis often affect fertility and/or have undesirable side effects that impede long-term management. Cannabis-based products have been suggested as a novel therapeutic option that may circumvent these issues. However, there is a paucity of well-designed, robust studies and randomized controlled trials looking at their use in the treatment of endometriosis. In addition, cannabis use has a potential for harm in the long term, with a possible association with "cannabis use disorder," psychosis, and mood disturbances. At present, national guidance cannot recommend cannabis-based products to patients in the UK owing to lack of clear evidence of benefit. More comprehensive research into the impact of endocannabinoids in the context of endometriosis is required before their use can be recommended or prescribed. (Copyright © 2021 AAGL. All rights reserved.)

Mitani, T., et al. (2024). "A prospective clinical trial of diathermy ablation for patients with high-grade cervical intraepithelial neoplasia from a single institution in Japan." Scientific Reports 14(1): 2632.
	Approximately 500,000 women are diagnosed with cervical cancer annually, with high-grade cervical intraepithelial neoplasia (CIN) estimated to be 20 times higher. The diathermy ablation is an inexpensive minimally invasive surgeries for CIN. However, little is known about the treatment outcomes. A prospective clinical trial was therefore conducted to evaluate ablation outcomes based on detailed colposcopy findings, cytology, and biopsy results over a two-year period. We enrolled CIN2 (n=32) and CIN3 (n=7) patients. Eligibility criteria included: aged between 29 and 49 (median: 36, mean: 36.3), visible transformation zone with high-grade lesions not entirely occupying the cervix, and histologically diagnosed with CIN2 or CIN3. Cytology and HPV genotyping were performed, and colposcopic findings were evaluated. Colposcopy-guided diathermy ablation was conducted by a certified gynecologic oncologist. The incidence of recurrent or residual disease was 5.1% (2/39, 95% confidence interval: - 0.02 to 0.12). The prevalence of HPV infection at 12 months decreased after surgery, as 67.6% (23/34, 0.52-0.83) of patients were HPV-negative. No severe adverse events were reported, while there were five pregnancies with full-term deliveries. The promising outcome was possibly due to selection of rigorous surgical indication and skilled surgical techniques. The study highlights the importance of experienced and skilled colposcopists.TrialRegistry This study was registered in the clinical trial registration system of the University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR ID: UMIN000024483). Open for the trial to the public through the website: 01/11/2016. First registration of the patient: 30/01/2017.Copyright © 2024. The Author(s).

Mitchell Caroline, M., et al. (2022). "Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal: Secondary Analysis of a Randomized Clinical Trial." JAMA Network Open 5(11): e2241743.
	Importance: Half of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention.; Objective: To compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal.; Design, Setting, and Participants: This is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022.; Interventions: Participants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks.; Main Outcomes and Measures: In this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics.; Results: A total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations.; Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain.; Trial Registration: ClinicalTrials.gov Identifier: NCT02516202.

Mitchell Caroline, M., et al. (2023). "The complexity of genitourinary syndrome of menopause: number, severity, and frequency of vulvovaginal discomfort symptoms in women enrolled in a randomized trial evaluating treatment for genitourinary syndrome of menopause." Menopause (New York, N.Y.) 30(8): 791-797.
	Objective: The aim of the study is to describe the location, severity, and frequency of genitourinary symptoms in postmenopausal women enrolled in a randomized trial of treatment for vulvovaginal discomfort.; Methods: This is a post hoc analysis of enrollment responses for participants in the MsFLASH Vaginal Health Trial. Participants were asked about the severity (0-3), frequency (in days per week) and location (vulvar or vaginal) of itch, dryness, pain/soreness, irritation, as well as severity and frequency of pain with penetration, vaginal discharge, urinary incontinence, and urinary urgency.; Results: A total of 302 participants were enrolled, with a mean age of 60.9 ± 4.1 years. The mean number of moderate-severe vulvovaginal symptoms experienced by trial participants in the month before enrollment was 3.4 ± 1.5, with a range from 1 to 7. The most commonly reported symptom across all severity categories was vaginal dryness (285/302, 94%), but the one most frequently rated as severe was pain with vaginal penetration (121/302, 40%). Vaginal dryness was the symptom with highest frequency; 53% of participants with that symptom reported experiencing it ≥4 d/wk. For vaginal symptoms, 80% of participants (241/302) reported that at least one of these symptoms occurred during or after sex while only 43% (158/302) reported that at least one vulvar symptom occurred during or after sex. Urinary incontinence (202/302, 67%) and urinary frequency (128/302, 43%) were the two most commonly reported urinary issues.; Conclusions: Our data highlight the complexity of genitourinary syndrome of menopause symptoms in quantity, severity, and frequency, suggesting that measuring distress, bother, or interference may be the most comprehensive measure.; Competing Interests: Financial disclosure/conflicts of interest: C.M.M. reports receiving grant funding from Scynexis, Inc, and has served as a consultant to Scynexis, Inc, Ferring Pharmaceuticals. S.D.R. receives research funding from Bayer, ongoing funding from UpToDate, and additional funding from the National Institutes of Health. The other authors have nothing to disclose. (Copyright © 2023 by The North American Menopause Society.)

Mitchell, J., et al. (2023). "Comparison of Postoperative Quality of Life Scores in Women Who Underwent Myomectomy Versus Hysterectomy for Uterine Fibroids." Obstetrics and Gynecology 141(5 Supplement 1): 19S.
	INTRODUCTION: Uterine fibroids are highly prevalent and associated with significant effect on quality of life (QOL). The current study compares QOL scores in patients that underwent myomectomy or hysterectomy for management of fibroids. METHOD(S): After obtaining approval from the Cleveland Clinic IRB, we conducted a retrospective cohort study for patients that underwent hysterectomy or myomectomy for uterine fibroids. Eligible patients were sent validated surveys: 36-Item Short Form Health Survey (SF-36) and Uterine Fibroid Symptom and QOL questionnaire (UFS-QOL). Standard bivariate analyses were used to compare differences in QOL scores between groups, adjusting for age and race. RESULT(S): Of the 142 survey respondents, 37 underwent myomec-tomy and 105 underwent hysterectomy. The median number of days between surgery and survey completion was 1,652 (1,142, 2,328) for myomectomy and 1,022 (740, 1,317) for hysterectomy. For SF-36, hysterectomy patients reported significantly less energy (P 5.006) compared to myomectomy. Significant differences were not observed in postoperative physical functioning, role limitations, pain, health perceptions, vitality, social functioning, or mental health. Although there was no statistically significant difference in UFS-QOL scores, patients who underwent hysterectomy experienced significantly lower symptom severity (P 5.009) and levels of concern (P,.001), and increased activity tolerance (P 5.005) and sense of control (P 5.029). CONCLUSION(S): While patients who underwent hysterectomy reported more fatigue, they experienced lower symptom severity, lower levels of concern, higher activity tolerance, and increased sense of control compared to myomectomy. These findings may help guide counseling for surgical fibroid treatment.

Mitchell, J.-B., et al. (2022). "Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety." BMC Women's Health 22(1): 526.
	Background: Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility.; Method & Outcome Measures: A systematic review of the literature was carried out using the databases Pubmed, Scopus, Cochrane and ClinicalTrials.gov in women with a confirmed laparoscopic diagnosis of endometriosis receiving progestins to determine a reduction in pain symptoms and the occurrence of adverse effects.; Results: Eighteen studies were included in the meta-analysis. Progestins improved painful symptoms compared to placebo (SMD = -0.61, 95% CI (-0.77, -0.45), P < 0.00001) with no comparable differences between the type of progestin. After median study durations of 6-12 months, the median discontinuation rate due to adverse effects was 0.3% (range: 0 - 37.1%) with mild adverse effects reported.; Conclusion: The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects.; Systematic Review Registration: PROSPERO CRD42021285026. (© 2022. The Author(s).)

Mitra, e. and K. Mohadese (2022). "The Effect of Complementary Medicine on Bacterial Vaginitis: A Systematic Review."
	
Mitranovici, M.-I., et al. (2022). "Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors." Diagnostics (Basel, Switzerland) 12(12).
	Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

Mitric, C., et al. (2023). "Cost impact analysis of enhanced recovery after minimally invasive gynecologic oncology surgery." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(11): 1786-1793.
	Objective: The implementation of a peri-operative care program based on enhanced recovery after surgery principles for minimally invasive gynecologic oncology surgery led to an improvement in same day discharge from 29% to 75% at our center. This study aimed to determine the program's economic impact.; Methods: Our initial enhanced recovery quality improvement program enrolled consecutive patients undergoing minimally invasive hysterectomy at a single center during a 12-month period and compared them to a pre-intervention cohort. The primary outcome was overall costs. The secondary outcomes were surgical and post-operative visit costs. The surgical visit costs included pre-operative and operating room, post-operative stay, pharmacy, and interventions costs. The 30-day post-operative visit costs included clinic and emergency room, and readmission costs. The costs for every visit were collected from the case-cost department and expressed in 2020 Canadian dollars (CAD).; Results: A total of 96 and 101 patients were included in the pre- and post-intervention groups, respectively. The median total cost per patient for post-intervention was $7252 compared with $8381 pre-intervention (p=0.02), resulting in a $1129 cost reduction per patient. The total cost for the program implementation was $134 per patient for a total cost of $13 106. The median post-operative stay cost was $816 post-intervention compared with $1278 pre-intervention (p<0.05). Statistically significant savings for the post-intervention group were also found for operative visit, operating room costs, and pharmacy (p<0.05). On multivariate analysis, surgical approach was the only factor associated with operating room costs, whereas both surgical approach and group (pre- vs post-intervention) impacted the total and post-operative stay costs (p<0.05).; Conclusion: In addition to increasing the same day discharge rate after minimally invasive gynecologic oncology surgery, an enhanced recovery-based peri-operative care program led to significant reductions in cost.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Mitsopoulos, V., et al. (2022). "Differences in Patterns of Recurrence Between Primary and Interval Debulking Surgery for Advanced Ovarian Cancer." Anticancer Research 42(4): 2003-2008.
	Background/aim: This study aimed to identify differences in the pattern and timing of recurrence in patients with advanced ovarian cancer undergoing primary (PDS) or interval debulking surgery after neoadjuvant chemotherapy (NACT).; Patients and Methods: Data were prospectively collected on 105 patients from June 2016 to March 2020.; Results: There were 30 (50%) recurrences in the PDS group compared to 32 (72.7%) in the NACT group (p=0.020). An intra-abdominal relapse was more common in NACT compared to PDS patients (64.4% vs. 38.3%, p=0.008) and a recurrence in two or more sites (NACT: 44.4% vs. PDS: 23.3%, p=0.010). Among completely cytoreduced patients, a pelvic recurrence was more frequent in NACT patients (NACT: 50% vs. 22.4% in PDS, p=0.011). Progression-free survival (PFS) was longer in PDS compared to NACT (27 vs. 16 months, p=0.039).; Conclusion: NACT patients experienced an unfavorable distribution and timing of recurrent disease compared to patient who underwent PDS. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Mitsuhashi, A., et al. (2022). "The effect of steep head-down tilt on respiratory status in endometrial cancer patients with obesity during robot-assisted hysterectomy." Gynecologic Oncology Reports 41: 101014.
	Objective: To evaluate the effect of head-down tilt on airway pressure in gynecologic patients with obesity during robot-assisted hysterectomy.; Methods: We retrospectively reviewed the records of 27 patients with body mass index (BMI) ≥ 25 kg/m 2 who underwent robot-assisted hysterectomy for endometrial cancer and endometrial atypical hyperplasia using the da Vinci Xi system. Mechanical ventilation was performed using pressure-controlled ventilation (PCV). Surgery was performed at 20° (group A, n = 17) or 25° head-down tilt (group B, n = 10). Respiratory parameters, including positive end-expiratory pressure (PEEP), tidal volume (TV), mean airway pressure (P mean), and peak airway pressure (P peak), were measured before (T1) and after the head-down tilt at 1 h (T2) and 2 h (T3) during anesthesia.; Results: The median BMI was 37.5 (range 28-51) kg/m 2 , with no between-group variation. Oxygenation was maintained intraoperatively for all patients. The expiratory carbon dioxide partial pressure was 43.6 (95% confidence interval (CI) 42.2-45.0) mmHg. The P mean peak at T2 in group B was significantly higher than in group A (P < 0.011); however, other parameters at T2 and T3 did not differ significantly between the groups. Patients with BMI ≥ 40 kg/m 2 had significantly higher respiratory parameters than those with BMI < 40 kg/m 2 . In patients with BMI ≥ 40 kg/m 2 , the mean P means and P peaks at T3 were 17.3 cmH 2 O (95% CI 16.3-18.3) and 29.4 cmH 2 O (95% CI 27.1-31.7), respectively.; Discussion: With careful anesthetic management during PCV, robot-assisted surgery with a head-down tilt of 25° or below may be safe, even in patients with class III obesity.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors.)

Mittal, M., et al. (2022). "The effect of micronized progesterone and medroxyprogesterone acetate in combination with transdermal estradiol on hemostatic biomarkers in postmenopausal women diagnosed with POI and early menopause: a randomized trial." Menopause (New York, N.Y.) 29(5): 580-589.
	Objective: To compare the impact of micronized progesterone (MP) or medroxyprogesterone acetate (MPA) in combination with transdermal estradiol (t-E2) on traditional coagulation factors and thrombin generation parameters in postmenopausal women diagnosed with premature ovarian insufficiency or early menopause.; Method: Randomized prospective trial conducted in women diagnosed with premature ovarian insufficiency or early menopause and an intact uterus, recruited over 28 months. All participants were prescribed t-E2 and randomized to either cyclical MP or MPA using a web-based computer randomization software, Graph Pad. Thrombin generation parameters were measured at baseline and repeated after 3-months. Traditional hemostatic biomarkers were measured at baseline and repeated after 3, 6, and 12-months. Seventy-one participants were screened for the study, of whom 66 met the inclusion criteria. In total, 57 participants were randomized: 44 completed the thrombin generation assessment arm of the study, whilst 32 completed 12-months of the traditional coagulation factor screening component of the trial.; Results: Thrombin generation parameters did not significantly change from baseline after 3-months duration for either progestogen component when combined with t-E2, unlike the traditional coagulation factors. Protein C activity, free Protein S, and Antithrombin III levels decreased with time in both treatment arms.; Conclusion: Fluctuations in traditional hemostatic biomarkers were not reproduced by parallel changes in thrombin generation parameters that remained neutral in both groups compared with baseline. The absence of statistically significant changes in thrombin generation for the first 3-months of hormone therapy use is reassuring and would suggest a neutral effect of both progestogens on the global coagulation assay.; Competing Interests: Financial disclosure/conflicts of interest: N.P. receives funding for being an advisor/speaker for Abbott, Bayer, Besins Gedeon Richter, Novo, SeCur, Theramex, and Viatris. The other authors have nothing to disclose. (Copyright © 2022 by The North American Menopause Society.)

Mitter, S., et al. (2022). "RIG-I as a potential new target for immunotherapies in endometrial cancer." Oncology Research and Treatment 45(Supplement 3): 117.
	Background: RIG-I (retinoic acid inducible gene I) increases expression and secretion of type-I-interferons, leading to recruitment of immune cells and induction of apoptosis. RIG-I is attributed a tumor-suppressive effect in various tumor entities such as melanoma. For endometrial cancer (EC), one of the most common gynecological malignancies and an immunogenic cancer, data about RIG-I as part of the innate immune system are missing. Our aim is to investigate the relationship between RIG-I expression and outcome in patients with EC. Method(s): Immunohistochemical staining was performed on 225 specimens of patients with EC. RIG-I expression was correlated with histopathological and survival data. Result(s): Elevated RIG-I levels correlated positively with advanced tumor stage and poor grading (FIGO stage p=0.027; T stage p=0.010; grading p=0.007). Overall survival was shorter in patients with high RIG-I levels (p=0.009). Furthermore, RIG-I was found to be an independent negative predictor of progression-free survival (p=0.022). Discussion and Conclusion(s): Our data establish RIG-I as a new marker for outcome in patients with EC. Compared to most other tumor entities where RIG-I seems to be tumorsuppressive, higher RIG-I-expression is associated with exactly the opposite effect in EC. In further studies, we are investigating the underlying mechanisms in more detail.

Mitter, V. R., et al. (2021). "Treatment following hysteroscopy and endometrial diagnostic biopsy increases the chance for live birth in women with chronic endometritis." American journal of reproductive immunology (New York, N.Y. : 1989) 86(5): e13482.
	PROBLEM: Repeated implantation failure and recurrent pregnancy loss are associated with chronic endometritis, a persistent endometrial inflammation. Its diagnosis and treatment may increase pregnancy and live birth rates. The aim of this study was to assess the effectiveness of endometrial diagnostic biopsy and subsequent antibiotic treatment in cases of chronic endometritis on reproductive outcomes over a long observation period. METHOD OF STUDY: We conducted a historical cohort study (2014-2018) at our University-based infertility center that included women (n = 108) with repeated implantation failure or recurrent pregnancy loss without known pathologies associated with either condition. Forty-one women underwent a hysteroscopy only (reference group); the remaining 67 women underwent, in addition to the hysteroscopy, an endometrial diagnostic biopsy with immunohistochemically staining for CD138 to detect plasma cells (biopsy group). If one or more plasma cells were detected, the women were treated with doxycycline 100 mg twice a day orally for 2 weeks. We performed stratified survival analysis (Kaplan-Meier) and Cox regression. RESULTS: The biopsy group had higher chances of pregnancy (hazard ratio 2.28; 95% confidence interval 1.23-4.24; p = .009) and of live birth (hazard ratio 2.76; 95% confidence interval 1.30-5.87; p = .008) compared with the reference group. In the sensitivity analysis, repeated implantation failure or recurrent pregnancy loss did not affect the outcome. CONCLUSION: Endometrial diagnostic biopsy followed by antibiotic treatment in case of chronic endometritis in women with repeated implantation failure or recurrent pregnancy loss may increase the chances for live birth.

Miwa, M. and K. Hasegawa (2022). "[Ⅲ. Recent Trends in Chemotherapy, Targeted Therapy and Immunotherapy for Cervical Cancer and Promising New Treatments]." Gan to kagaku ryoho. Cancer & chemotherapy 49(2): 155-160.
	
Miyakoshi, J., et al. (2022). "Clinical outcomes and appropriate treatment strategies of locally advanced resectable cervical esophageal cancer." Journal of Clinical Oncology 40(4 SUPPL).
	Background: Due to its rare nature, no standard treatment based on the randomized controlled trials for locally-advanced resectable cervical esophageal cancer (rCEC) has been established. Prognostic factors of locally-advanced rCEC are not also well evaluated. When considering the treatment for rCEC, larynx preservation (LP) is an important issue, as well as the prolongation of survival. This study aimed to clarify the clinical outcomes and prognostic factors on locally-advanced rCEC, and the appropriate treatment strategies focused on both LP and long-term survival. Method(s): We retrospectively reviewed the medical records of rCEC patients treated with surgery or definitive chemoradiotherapy (CRT) at our institute from 2010 to 2020. This retrospective study was approved by the institutional review board of NCCH (2017-229). Result(s): A total of 123 cases were extracted as subjects, treated with surgery in 53 and CRT in 70. 1/3/5-year PFS and OS in all subjects were 52/40/36% and 84/60/56%, respectively. Univariate analysis indicated that clinical tumor depth might be a prognostic factor (T1 vs. T>=2, hazard ratio [HR]: 2.30, p=0027. in PFS; HR: 2.86, p=0.046 in OS). In the subjects with >=T3 lesion (N=95) who usually require laryngectomy, both PFS (31.0 vs. 7.0 months, HR: 0.50, p=0.013) and OS (not reached vs. 25.0 months, HR: 0.28, p=0.005) were better in subjects treated with surgical approach than with CRT. Focused on the cases with >=T3 lesion and initially treated with induction chemotherapy (N=33), the surgical approach also showed better clinical outcomes than the CRT approach (median PFS: 19.0 vs. 8.0 months, HR: 0.37, p=0.007; median OS: not reached vs. 18.0 months, HR: 0.18, p=0.007). Especially, subjects treated with induction chemotherapy followed by larynx-preserving surgery achieved better outcomes. Conclusion(s): This study indicated that clinical depth might be a significant prognostic factor in rCEC. A chemoselection approach using induction chemotherapy might be a good strategy to achieve LP and improve survival outcomes in locally-advanced rCEC.

Miyamoto, T., et al. (2023). "ACTIVATION OF MYELOID CELLS SUPPRESSES METASTATIC OVARIAN CANCER VIA TUMORICIDAL NEUTROPHILS AND IL-27-SECRETING MACROPHAGES." Journal for Immunotherapy of Cancer 11(Supplement 1): A1212.
	Background Eradication of intraperitoneal metastasis of ovarian cancer (OC) remains an unmet challenge. Current T cell-mediating immunotherapies have not been applied to OC due to lack of efficacy in most patients. Immunosuppressive myeloid cells associate with tumor progression and treatment resistance in the metastatic sites of OC. The purpose of this study is to develop a novel immunotherapy that activates myeloid cells with the goal of eradicating metastatic OC. Methods Recently established, clinically relevant murine OC cells, that are homologous recombination proficient, KPCA (KRASG12VTrp53R172HCcne1OEAkt2OE), were intraperitoneally injected to build the murine metastatic OC model. b-glucan and interferon (IFN) g were used to activate myeloid cells. bglucan is a yeast cell wall polysaccharide that is currently in clinical trials to treat multiple cancers. It canonically activates myeloid cells through the Dectin-1 pathway and induces infiltration of monocytes and neutrophils. IFNgamma activates macrophages to an anti-tumor status. Tumor burden and tumor microenvironment in the ascites and omentum were evaluated using bioluminescence imaging, confocal imaging, flow cytometry, and single-cell RNA sequencing (scRNA seq) to investigate whether and how b-glucan modulates metastatic OC with or without IFNgamma. Furthermore, OC patient survival was analyzed based on gene expression using public dataset. Finally, combination of myeloid cell activation with carboplatin was tested. Results b-glucan alone was efficient in clearing ascites, although it did not affect total metastases. On the other hand, combining b-glucan with IFNgamma (b-glucan/IFNgamma) not only cleared ascites but also reduced total metastases compared to PBS-, b-glucan-, or IFNgamma-treated mice. This anti-tumor immunity required T cells and non-tumor IFNgamma signaling in the host. scRNA seq of omental tumors revealed b-glucan/IFNgamma induced the enrichment of a unique subset of neutrophils and macrophages compared to other groups. The neutrophil subset upregulated Camp and Ltf, which are granule proteins known to have tumoricidal function. Eukaryotic initiation factor-2 signaling, which is associated with reactive oxygen species (ROS) production, is the most upregulated pathway in the neutrophil subset. The macrophage subset selectively expressed interleukin (IL)-27, which has anti-tumor potential mainly through T cells. Blocking IL-27 significantly impaired the anti-tumor response of b-glucan/IFNgamma. OC patients with high expression of these genes identified in the novel myeloid cell subsets correlate with better overall survival. Finally, combining b-glucan/IFNgamma with carboplatin nearly eradicated chemoresistant KPCA tumors. Conclusions b-glucan/IFNgamma suppressed metastatic OC enriching anti-tumor myeloid cell populations. Combination therapy of this myeloid cell activation and standard-of-care chemotherapy could potentially transform treatments against metastatic OC.

Miyoshi, A. I., et al. (2023). "Recent Advances in the Management of Small Cell Carcinoma of the Uterine Cervix." Anticancer Research 43(4): 1397-1405.
	Background/aim: Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a rare disease characterized by a higher incidence of lymphatic invasion, metastasis, and recurrence compared to the squamous cell carcinoma and adenocarcinoma subtypes. Furthermore, it is prone to early distant metastasis and has a poor prognosis. Chemotherapy has an important role in the management of cervical SCNEC. The effective treatment schemes for early-stage SCNEC are local treatment with radical surgery and systemic chemotherapy. However no standard treatment regimen exists because of a rare disease. We reviewed previous reports to determine whether etoposide/platinum, which is used for histopathologically similar small cell carcinoma of the lung, is an appropriate initial chemotherapy regimen for SCNEC of the cervix.; Materials and Methods: In this review the Cochrane library sources, ClinicalTrials.gov, Web of Silence, PubMed and search engine of Google scholar were searched for all interventional studies, reviews, case reports and meta-analyses published in 1997-2021.; Results: Etoposide/platinum (EP) is the most commonly used regimen and paclitaxel/carboplatin is the second most common, used as a part of multimodality therapy for SCNEC of the cervix in most studies. Cisplatin/vincristine/bleomycin, cisplatin/irinotecan, cisplatin/ifosfamide/etoposide were also reported in concurrence with EP; however no clinical trials are dedicated to SCNEC.; Conclusion: Etoposide and platinum tend to have a better prognosis compared to other regimens used for other subtypes of cervical cancer. For recurrent cervical SCNEC, treatment options for patients are very limited. The application of molecular testing for targeted mutations may suggest potential future therapies that may be useful in this disease. (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Mizuno, H., et al. (2024). "End-to-end dosimetry audit for three-dimensional image-guided brachytherapy for cervical cancer." Physica Medica 119: 103321.
	Background: End-to-end dosimetry audit for brachytherapy is challenging due to the steep dose gradient. However, it is an efficient method to detect unintended errors in actual clinical practice. Purpose(s): We aimed to develop an on-site end-to-end test phantom for three-dimensional image-guided brachytherapy (IGBT) for cervical cancer. Method(s): The test phantom we developed consisted of a water tank with an applicator/detector holder. The holder was designed to accommodate the applicator and insert an ionization chamber (PinPoint; PTW, Freiburg, Germany) to measure the dose at point A. Imaging and reconstruction were performed in the same way as performed for a patient. The feasibility of our test phantom was assessed in two different hospitals using tandem and ovoid (made of either metal or carbon) applicators that the hospitals provided. Result(s): The measured and calculated doses at point A were compared for each applicator. We observed that the values obtained using metal applicators were consistently lower, on an average by -2.3%, than the calculated values, while those obtained using carbon applicators were comparable to the calculated values. This difference can be attributed to the attenuation of the dose by the metal applicators, resulting in a lower dose at point A. The majority of treatment planning system, including the one used in this study, do not account for the material of applicator. Conclusion(s): An end-to-end test phantom for IGBT was developed, tested, and applied in a dosimetry audit in hospitals and showed favorable results for evaluating the point A dose.Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria

Mo, D.-C., et al. (2021). "Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review." International immunopharmacology 91: 107281.
	Objective: Both pembrolizumab and lenvatinib demonstrate antitumor activity and safety in cancers. However, whether their combination is safer and more effective than monotherapies remains unknown. A systematic review was performed to assess the safety and efficacy of pembrolizumab plus lenvatinib versus their respective monotherapies in solid cancers.; Methods: PubMed, Embase, and Cochrane Library were searched. Forty-two clinical trials with 8155 patients were included.; Results: The total ≥grade 3 adverse events (AEs) and objective response rates (ORRs) among pembrolizumab plus lenvatinib and pembrolizumab or lenvatinib monotherapies in solid cancers were 68.0% vs 17.7% vs 68.5% and 40.6% vs 20.8% vs 43.3%, respectively. The most common AEs of pembrolizumab plus lenvatinib were hypertension (20-61.1%), fatigue (12-59.1%), diarrhea (9-51.9%), hypothyroidism (25-47%), and proteinuria (8-17%). Good ORRs for combination therapy were observed in renal cell carcinoma (70%), gastric cancer (69%), melanoma (48%), head and neck squamous cell carcinoma (46%), and endometrial cancer (38-53%), while these rates were reported as 27%, 11.6-22%, 26-37%, 14.6-23%, and 11-14.3% for monotherapies, respectively. Longer median progression-free survival (mPFS) and median overall survival (mOS) were observed for hepatocellular carcinoma (mPFS 9.3 months, mOS 22.0 months), renal cell carcinoma (mPFS 19.8 months), gastric cancer (mPFS 7.1 months, mOS not reached), and endometrial cancer (mPFS 7.4 months, mOS 16.7 months).; Conclusions: Compared with their monotherapies, pembrolizumab plus lenvatinib showed more promising antitumor activity and resulted in higher ORRs and significant survival benefits in the above cancers. Toxicities were manageable, with no unexpected safety issues. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mo, J., et al. (2023). "Effectiveness of traditional Chinese medicine formulas combined with acupuncture in the treatment of ovulation dysfunction infertility: A systematic review and meta-analysis." Medicine 102(27): e34310.
	Background: To evaluate the efficacy and safety of traditional Chinese medicine formulas combined with acupuncture for the treatment of ovulation dysfunction infertility (ODI).; Methods: From January 1, 2018 to March 12, 2023, 7 electronic databases, PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang Database, and CBM, were systematically searched to identify eligible randomized controlled trial studies.; Results: Meta analysis showed that traditional Chinese medicine combined with acupuncture can more effectively improve sex hormone levels compared to Western medicine alone, including follicle stimulating hormone (FSH) in older patients (standardized mean difference [SMD]: 3.00; 95% confidence interval [CI]: 2.35-3.66; P = .024, I 2 = 28%), FSH in younger patients (SMD: 0.45; 95% CI: -0.15, 1.05; P = .03, I 2 = 71%), estradiol (E2) (SMD: 7.50; 95% CI: v0.47, 15.48; P < .00001, I 2 = 99%), and progesterone (P) (SMD: 2.20; 95% CI: 2.07-2.33; P < .00001, I 2 = 29%). Compared to Western medicine alone, traditional Chinese medicine combined with acupuncture also had a better effect to increase ovulation rate (risk ratio [RR]: 2.46; 95% CI: 1.72-3.52; P < .00001, I 2 = 0%), pregnancy rate (RR: 2.50; 95% CI: 1.96-3.18; P < .00001, I 2 = 0%), maximum follicle diameter (MFD) (SMD: 2.27; 95% CI: 1.37-3.16; P < .00001, I 2 = 91%), and endometrial thickness (SMD: 1.71; 95% CI: 1.31-2.11; P < .00001, I 2 = 87%). The combination of traditional Chinese medicine and acupuncture also had better effects on quality of life (RR: 0.19; 95% CI: 0.15-0.23; P < .00001, I 2 = 0%) and reduced adverse reactions (RR: 0.15; 95% CI: 0.05-0.48; P = .001, I 2 = 0%), compared to Western medicine alone.; Conclusion: This study shows evidence that traditional Chinese medicine formulas combined with acupuncture are an effective and safe treatment approach. However, this conclusion requires further confirmation due to the insufficient quality of the included trials.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Moayedi, G., et al. (2022). "Intranasal fentanyl for first-trimester uterine aspiration pain: A randomized controlled trial." Contraception 113: 101-107.
	Objective: To evaluate whether administration of intranasal fentanyl reduces reported pain during first-trimester uterine aspiration.; Study Design: We conducted a multicenter, randomized, double-blind, placebo-controlled trial of patients with pregnancies less than or equal to 14 weeks gestation seeking uterine aspiration for induced abortion, early pregnancy loss, or failed medication abortion. We randomized participants 1:1 to either intranasal fentanyl 100 mcg or intranasal placebo. All participants received ibuprofen and a standardized paracervical block. The primary outcome was pain indicated at the time of uterine aspiration on a 100 mm visual analog scale (VAS). We designed the study to detect a 15 mm difference in mean pain scores, which required 53 people in each arm for a total of 106 participants. Secondary outcomes included postprocedure pain and patient satisfaction with pain control.; Results: From March 2017 through June 2018, we screened 355 people for eligibility and enrolled 107 participants. Those who received intranasal fentanyl reported similar uterine aspiration pain to participants who received placebo (58.4 ± 28.0 fentanyl vs 58.6 ± 24.5 placebo, p = 0.97). Participants who received intranasal fentanyl also reported similar postprocedure pain scores compared to participants who received placebo (19.1 ± 19.4 fentanyl vs 17.2 ± 19 placebo, p = 0.63), and were equally satisfied with procedure pain control (66.8 ± 31.2 fentanyl vs 63.3 ± 29.2 placebo, p = 0.57).; Conclusion: Intranasal fentanyl did not decrease reported pain with first-trimester uterine aspiration, nor did it decrease postprocedure pain compared to placebo. As an adjunct to ibuprofen and paracervical block, intranasal fentanyl did not improve patient satisfaction with pain control.; Implications: Intranasal fentanyl does not reduce reported pain with first-trimester uterine aspiration, however abortion-seeking patients are amenable to receiving intranasal medications for pain management. (Copyright © 2022. Published by Elsevier Inc.)

Moccia, F., et al. (2023). "Injection Treatments for Vulvovaginal Atrophy of Menopause: A Systematic Review." Aesthetic plastic surgery 47(6): 2788-2799.
	Background: Injection treatments have been proposed as novel treatment options for Vulvovaginal Atrophy of Menopause (VVA) also known as Genitourinary Syndrome of Menopause (GSM). However, to date data about these treatments are poor.; Objective: To assess all available injection treatments for VVA.; Methods: A systematic review was performed by searching five electronic databases for peer-reviewed studies that assessed injection treatments for VVA.; Results: Eight studies (7 observational and 1 randomized) with 236 women were included. Assessed injection materials were: autologous platelet-rich plasma (PRP) + hyaluronic acid (HA), not cross-linked HA plus calcium hydroxyapatite (NCLHA + CaHA), micro-fragmented adipose tissue (MFAT), hyaluronan hybrid cooperative complexes (HCC), crosslinked HA, microfat and nanofat grafting + PRP, and PRP alone. Improvement in GSM symptoms after treatment was assessed through Visual Analogic Scale (VAS) for GSM symptoms or patient satisfaction, several validated questionnaires (FSFI, VHI, FSD, SF12, ICIQ UI SF, PGI-I, FSDS-R, VSQ), symptoms severity, changes in vaginal mucosa thickness, flora, pH, and expression on vaginal mucosal biopsies of Procollagen I and III and ki67 immunofluorescence or COL1A1 and COL3A1 mRNA. Injection treatments showing significant improvement in GSM-related symptoms were: (i) HCC in terms of VAS for GSM symptoms and FSFI score; (ii) Crosslinked HA in terms of VAS for GSM symptoms, FSFI and VHI score, COL1A1 and COL3A1 mRNA expression on vaginal mucosal biopsies; (iii) NCLHA + CaHA in terms of FSFI score; (iv) PRP + HA in terms of VHI, FSD and SF12 score; (v) microfat and nanofat grafting + PRP in terms of VHI score and FSDS-R score; (vi) PRP alone in terms of VHI and VSQ scores.; Conclusions: All assessed injection treatments except for MFAT seem to lead to significant improvement in VVA symptoms on validated questionnaires. Further studies are necessary in the field.; Level of Evidence Ii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Modarres Shahrzad, Z., et al. (2023). "Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study." The Indian journal of medical research 157(1): 66-73.
	Background & Objectives: Studies have shown that insulin resistance and hyperinsulinaemia play a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, the use of insulin sensitizing drugs in the treatment of PCOS has attracted the attention of medicine and researchers. The aim of this study was to investigate the effects of sitaformin (sitagliptin/metformin) and metformin on the quality of oocyte and embryo in classic PCOS patients undergoing intracytoplasmic sperm injection (ICSI).; Methods: Sixty patients of PCOS (25-35 yr) were randomly allocated into three groups (n=20, each group): a metformin-treated group (administered metformin 500 mg twice daily), a sitaformin-treated group (administered sitaformin 50/500 mg twice daily) and a placebo group. Participants in all the groups received the drug two months prior to the start of the ovulation cycle and treatment continued until the day of the oocyte aspiration.; Results: Serum insulin and total testosterone levels decreaseed significantly after treatment in both the treatment groups as compared to the placebo (P<0.05). A significant decrease in the number of immature oocytes [MI + germinal vesicle (GV) stage] was observed in metformin and sitaformin groups as compared to the placebo. In addition, sitaformin group when compared to the metformin group showed a significant decrease in the number of immature oocytes (P<0.05). The number of mature and normal MII oocytes increased significantly in both the treatment groups compared to the placebo group (P<0.05). The number of mature and normal oocytes increased in sitaformin group in comparison to the metformin group, but the difference was not significant. There was a significant increase in the number of grade I embryos, fertilization and cleavage rates in the sitaformin group compared to the other groups (P<0.05).; Interpretation & Conclusions: This is the first study to compare the impact of sitaformin with metformin on oocyte and embryo quality in women with PCOS undergoing a gonadotropin-releasing hormone (GnRH) antagonist cycle. In conclusion, sitaformin can be more effective in decreasing immature oocytes and increasing the quality of embryos than the use of metformin.

Moderie, C., et al. (2021). "Effects of exogenous melatonin on sleep and circadian rhythms in women with premenstrual dysphoric disorder." Sleep: Journal of Sleep and Sleep Disorders Research 44(12): 1-11.
	We previously found normal polysomnographic (PSG) sleep efficiency, increased slow-wave sleep (SWS), and a blunted melatonin secretion in women with premenstrual dysphoric disorder (PMDD) compared to controls. Here, we investigated the effects of exogenous melatonin in five patients previously studied. They took 2 mg of slow-release melatonin 1 h before bedtime during their luteal phase (LP) for three menstrual cycles. At baseline, patients spent every third night throughout one menstrual cycle sleeping in the laboratory. Measures included morning urinary 6-sulfatoxymelatonin (aMt6), PSG sleep, nocturnal core body temperature (CBT), visual analog scale for mood (VAS-Mood), Prospective Record of the Impact and Severity of Menstrual Symptoms (PRISM), and ovarian plasma hormones. Participants also underwent two 24-hour intensive physiological monitoring (during the follicular phase and LP) in time-isolation/constant conditions to determine 24-hour plasma melatonin and CBT rhythms. The same measures were repeated during their third menstrual cycle of melatonin administration. In the intervention condition compared to baseline, we found increased urinary aMt6 (p < 0.001), reduced objective sleep onset latency (p = 0.01), reduced SWS (p < 0.001), and increased Stage 2 sleep (p < 0.001). Increased urinary aMt6 was correlated with reduced SWS (r = -0.51, p < 0.001). Circadian parameters derived from 24-hour plasma melatonin and CBT did not differ between conditions, except for an increased melatonin mesor in the intervention condition (p = 0.01). Ovarian hormones were comparable between the conditions (p >= 0.28). Symptoms improved in the intervention condition, as measured by the VAS-Mood (p = 0.02) and the PRISM (p < 0.001). These findings support a role for disturbed melatonergic system in PMDD that can be partially corrected by exogenous melatonin. (PsycInfo Database Record (c) 2022 APA, all rights reserved) Impact Statement Reduced melatonin secretion and increased slow-wave sleep were previously found in women with premenstrual dysphoric disorder (PMDD) and insomnia compared to controls. Using a within-subject design, we studied women with PMDD and insomnia across a full menstrual cycle before and after the administration of 2 mg of slow-release melatonin. We have shown a reduction in slow-wave sleep and in self-reported PMDD symptoms after administrating exogenous melatonin. These changes may relate to an abnormal MT1/MT2 ratio and appear independent from melatonin effects on circadian phase, temperature, or steroidogenesis. This study could pave the way for new treatments of PMDD. A large randomized-controlled trial for slow-release exogenous melatonin as an adjunct/treatment in PMDD is warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Modesitt, S. C., et al. (2021). ""Moving Away From Cancer" Prospective Exercise Trial for Female Rural Cancer Survivors: How Can We Step It Up?" JCO oncology practice 17(1): e16-e25.
	PURPOSE: This prospective trial's objective was to determine feasibility and outcomes of an exercise-based intervention for rural overweight/obese female cancer survivors. MATERIALS AND METHODS: Survivors of endometrial, breast, or ovarian cancer enrolled in a 6-month program of increased aerobic activity (30 minutes daily walking) and strength-training exercises using exercise bands (THERABAND; Akron, OH) with personalized telephone motivational coaching. Baseline demographics, anthropomorphic measurements, quality of life (QOL), fitness, and readiness to adopt exercise changes were assessed; daily steps, band use, and follow-up measurements were assessed at 3 and 6 months. Study completion was modeled using logistic regression. RESULTS: The mean age of the 99 women was 59.9 years, the mean body mass index (BMI) was 35.9 kg/m2, 88.9% were white, and 41.4% reported current exercise. Fifty-five women (55.6%) completed the 6-month program, and 36 (36.4%) completed exercise interventions. Using logistic regression to model study completion, only baseline QOL scores (physical component summary) and mental component summary) remained significant predictors. The mean weight change was a gain (0.88 kg). Higher MCS baseline scores and prior regular exercise predicted continued exercise and increased step counts, whereas higher BMI and baseline sleep predicted decreased QOL. Top walking barriers were feeling unwell and weather; barriers to strength exercises were band dislike and pain. CONCLUSION: The most significant predictor of trial completion and improved exercise outcomes was a higher baseline mental QOL. Motivation, belief in the importance of exercise, and prescribed/monitored exercise regimens were not sufficient; supportive and cognitive behavioral therapy interventions for survivors are needed to sustain uptake.

Moeini, R., et al. (2024). "Pomegranate effects on the health aspects of women during peri- and postmenopause: A systematic review and meta-analysis." Phytotherapy research : PTR 38(1): 368-383.
	Pomegranate is widely used to preserve human health and help prevent many kinds of diseases. This study aims to review and assess the effects of pomegranate on women's health during and after menopause. PubMed, Web of science, Cochrane, Scopus, and Google Scholar were searched up to the end of 2022 with no language or study type restriction. All types of clinical research studies (randomized clinical trial [RCT], pre-post, case report, and case series) were included. The Cochrane RoB 2.0 tool was used for quality assessment of RCTs. A summary of intervention's effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence interval using random effect model. Weighted mean differences and heterogeneity between studies were assessed using Hedges's method and Cochran's Q test, respectively. Pomegranate can significantly improve hot flashes severity and menopause symptoms and decrease FSH. It significantly improves high-density lipoprotein but not low-density lipoprotein, body mass index, and weight. Most of our results are inconclusive, and the small sample sizes and the lack of blinding and randomization have led to an increased risk of bias. Pomegranate can decrease menopause symptoms, but more well-designed studies, with bigger sample sizes are needed to establish its other clinical benefits for menopausal women. (© 2023 John Wiley & Sons Ltd.)

Moffat, G. T., et al. (2022). "Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian cancer." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: In the pivotal Aurelia study, addition of bevacizumab (bev) to physician's choice chemotherapy (paclitaxel, liposomal doxorubicin or topotecan) for platinum-resistant (PL-R) ovarian cancer (OC) was associated with improved progression-free survival (PFS; 6.7 vs 3.4 mos; hazard ratio (HR) 0.48, p = 0.001) but not overall survival (OS; 16.6 vs 13.3 mos HR 0.85, p = 0.174); the latter finding may relate to extensive crossover. In an exploratory subgroup analysis by treatment arm, benefits were particularly marked for bev + paclitaxel where median PFS (mPFS) increased from 3.9 to 10.4 mos (HR 0.46; 95%CI 0.30-0.71) and increases in OS approached statistical significance (HR 0.65; 95%CI, 0.42-1.02; 22.4 v 13.2 mos). Here we describe utilization of bev for PL-R OC and outcomes in routine clinical practice. Method(s): The Ontario Cancer Registry and the New Drug Funding Program databases were utilized to identify all patients treated with bev plus chemotherapy (paclitaxel, liposomal doxorubicin or topotecan) for PL-R OC following its approval in 2017. Time on treatment (ToT) was defined as time from first to last bev treatment; this was used as a surrogate for PFS in routine practice. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with ToT and OS were identified using a Cox proportional hazard model. A before and after comparison analysis was performed to determine mOS for patients treated pre-(2011-2017) and post-bev (2017-2019) approval. Result(s): From Oct 2017 to Dec 2019, 180 patients received bev + chemotherapy for first-line PL-R OC. Mean age was 63 years old, and 80% had serous OC. Bev was most often combined with liposomal doxorubicin (64 %) followed by paclitaxel (34%) and topotecan (2%). Median ToT was 3 months and OS was 11 months. ToT and OS were longer in patients who received paclitaxel as chemotherapy backbone (5 mos [ToT]; 14 mos [OS]) than those who received bev with liposomal doxorubicin (2 mos; 9 mos) or topotecan (2 mos; 6 mos). In multivariable models, ToT was superior in patients who received bev + paclitaxel than bev + liposomal doxorubicin (HR 0.40; 95%CI 0.28-0.57; p < 0.0001), and worse with longer time from diagnosis to bev start (1.03; 1.01-1.05; p = 0.0120). OS was also significantly longer in those who received paclitaxel vs liposomal doxorubicin (HR 0.54; 95%CI 0.30-0.98; p = 0.043). In a before and after analysis, patients treated in the pre-(n = 1290) and post-bev (n = 360) era had mOS of 8 and 9 months respectively. Post mOS increased for patients receiving paclitaxel (7 vs 12 months) but not with liposomal doxorubicin (9 vs 7 months). Conclusion(s): ToT and OS associated with bev for PL-R OC are shorter in a real-world population compared to results reported in AURELIA. ToT and OS were longer with bev + paclitaxel than with other chemotherapy agents.

Moffat, R., et al. (2021). "Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders." Human Reproduction 36(4): 987-997.
	STUDY QUESTION: Does the gonadotropin (GN) starting dose and the addition of clomiphene citrate (CC) during the early follicular phase influence oocyte yield in poor responders undergoing ovarian stimulation for IVF treatment? SUMMARY ANSWER: The number of retrieved oocytes was similar regardless of the starting dose of GN (150 versus 450 IU) with or without the addition of CC (100 mg from Day 3 to 7 versus placebo). WHAT IS KNOWN ALREADY: ART in poor responders is a challenge for patients and clinicians. So far, randomised controlled studies addressing interventions have shown that neither the GN dose nor the addition of oral medication has any significant effect on the clinical outcome of ART in poor responders. There is limited knowledge about the effect of GN starting dose in combination with CC during the early follicular phase of ovarian stimulation on ovarian response markers and ART outcome. STUDY DESIGN, SIZE, DURATION: This single-centre randomised double-blinded clinical trial was conducted from August 2013 until November 2017. Using the Bologna criteria, 220 of 2288 patients (9.6%) were identified as poor responders and 114 eligible participants underwent ovarian stimulation in a GnRH-antagonist protocol for ART. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were equally randomised to one of four treatment arms: Group A (n = 28) received 100 mg CC (Day 3-7) and a starting dose of 450 IU HMG, Group B (n = 29) received 100 mg CC and a starting dose of 150 IU HMG, Group C (n = 30) received placebo and a starting dose of 450 IU HMG and Group D (n = 27) received placebo and a starting dose of 150 IU HMG. Serum levels of FSH, LH, estradiol and progesterone were measured on Day 1 and 5 and on the day of ovulation induction. Available embryos were cultured up to the blastocyst stage and were always transferred in the same cycle. The primary outcome was the number of oocytes collected after ovarian stimulation. Other outcome measures were response to ovarian stimulation, embryo development and obstetrical outcome. MAIN RESULTS AND THE ROLE OF CHANCE: All study participants (n = 114) fulfilled at least two of the Bologna criteria for poor responders. Median age of the study population was 38.5 years. There were 109 patients who underwent oocyte retrieval. The number of oocytes retrieved was similar among the groups (±SD; 95% confidence intervals); A: 2.85 (±0.48; 2.04-3.98), B: 4.32 (±0.59; 3.31-5.64); C: 3.33 (±0.52; 2.45-4.54); D: 3.22 (±0.51; 2.36-4.41); P overall = 0.246. However, ovarian stimulation with 150 IU plus CC resulted in a higher number of blastocysts compared to ovarian stimulation with 450 IU plus CC (±SD; 95% confidence intervals); A: 0.83 (±0.15; 0.58-1.2), B: 1.77 (±0.21; 1.42-2.22); P overall = 0.006. Mean FSH serum levels were lower in the groups with a starting dose of 150 IU. Adding CC did not affect mean serum FSH levels. There were no differences in estradiol concentrations among the groups. Endometrial thickness was lower in the groups receiving CC. The overall live birth rate (LBR) was 12.3%, and the cumulative LBR was 14.7%. LIMITATIONS, REASONS FOR CAUTION: The trial was powered to detect differences in neither the number of blastocysts nor the LBR, which would be the preferable primary outcome of interventional trials in ART. WIDER IMPLICATIONS OF THE FINDINGS: We found that ovarian stimulation with 150 IU gonadotrophin in combination with 100 mg CC produced more blastocysts. The effect of adding CC to GN on LBR in poor responders remains to be proven in randomised trials. High GN doses (450 IU) resulted in high FSH serum levels but increased neither the estradiol levels nor the number of retrieved oocytes, implying that granulosa cell function is not improved by high FSH serum levels. Lower starting doses of GN lead to a reduction of costs of medication. The small but significant difference in blastocyst formation and the lower FSH levels in the treatment groups receiving less GN may be an indication of better o cyte quality with higher developmental competence. STUDY FUNDING/COMPETING INTEREST(S): The costs for the HMG used for ovarian stimulation were provided by IBSA Switzerland. The study was also supported by the Repronatal Foundation, Basel, Switzerland. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: NCT01577472. TRIAL REGISTRATION DATE: 13 April 2012. DATE OF FIRST PATIENT’S ENROLMENT: August 2013.

mohammad, f., et al. (2022). "sodium glucose co-transporter 2 inhibitors versus metformin in management of polycystic ovary syndrome."
	
Mohammad-Akbari, A., et al. (2022). "The effect of low-molecular-weight heparin on live birth rate of patients with unexplained early recurrent pregnancy loss: A two-arm randomized clinical trial." Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 27: 78.
	Background: The effect of anticoagulant medication in unexplained early recurrent pregnancy loss (RPL) patients is controversial. This clinical trial evaluated the effect of low-molecular-weight heparin (LMWH) on pregnancy outcomes in these patients.; Materials and Methods: The study was performed as a single-blind randomized clinical trial between 2016 and 2018. Samples were selected from patients who were referred to Avicenna RPL clinic with a history of at least two previously happened early unexplained miscarriages. The eligibility was defined strictly to select unexplained RPL patients homogenously. One hundred and seventy-three patients who got pregnant recently were allocated randomly into two groups LMWH plus low-dose aspirin treatment (Group A = 85) and low-dose aspirin treatment only (Group B = 88)) and were followed up till their pregnancy termination (delivery/abortion). A per-protocol analysis was carried out and all statistical tests were two-sided with a P < 0.05 significance level.; Results: The live birth rates (LBRs) in Groups A and B were 78% and 77.1%, respectively, which did not show any statistically significant difference between the two groups, neither in rates nor in time of abortion. In subgroup analysis for polycystic ovary syndrome (PCOS) patients, the odds ratio for study outcome (intervention/control) was 2.25 (95% confidence interval: 0.65-7.73). There was no major adverse event whereas minor bleeding was observed in 18% of patients in Group A.; Conclusion: LMWH does not improve the LBR in unexplained RPL patients, however, it is recommended to evaluate its effect separately in PCOS patients.; Competing Interests: There are no conflicts of interest. (Copyright: © 2022 Journal of Research in Medical Sciences.)

Mohammadbeigi, R., et al. (2022). "Evaluation of Nifedipine Administration on Embryo Transfer Success Rate: a Randomized Clinical Trial." Journal of advances in medical and biomedical research 30(141): 314‐318.
	Background & Objective: In‐vitro fertilization (IVF) is one of the approved treatment options for infertility. Despite many progresses in this field, its success rate is about 20‐25%. Utilization of drugs which suppress or decrease uterine smooth muscle contraction before embryo transfer, theoretically can improve fertility by increasing implantation rate. This study was designed to evaluate nifedipine administration on embryo transfer success. Materials & Methods: In this double blinded randomized clinical trial, ninety‐eight infertile women from primary and secondary causes were included in two groups; one group received placebo and the other group a single dose of 20 mg nifedipine, both thirty minutes before embryo transfer. Primary outcome was defined as clinical pregnancy, and secondary outcomes as live birth, ectopic pregnancy, multiple gestation and abortion. Results: Clinical pregnancy occurred in eighteen patients in the placebo group and in seventeen patients in nifedipine group (OR = 0.91, 0.40‐2.09 (95% CI)). Sixteen patients in placebo group and fourteen patients in nifedipine group had successful live births (OR = 0.82, 0.34‐1.95 (95% CI)). Multiple gestation (OR = 1.71, 0.24‐11.78 (95% CI)) and abortion (OR = 0.46, 0.07‐2.95 (95% CI)) were not different between the two groups. No side effect of drug occurred in any group. Conclusion: single dose of 20 mg nifedipine tablet administered thirty minutes before IVF had no effect on improving clinical pregnancy and live birth rate. Using higher doses, or different regimens in specific patients’ subgroups may have more effect on embryo transfer success.

Mohammadi, A., et al. (2021). "Analgesic effects and hemodynamic mechanisms of perpendicular and transverse needling at Sanyinjiao (SP 6) in patients with primary dysmenorrhea: a randomized controlled trial." Journal of Traditional Chinese Medical Sciences 8(3): 248‐256.
	Objective: To explore the analgesic effects and uterine hemodynamics of perpendicular needling (PN) and transverse needling (TN) at SP 6 in patients with primary dysmenorrhea (PD). Methods: In this randomized controlled trial, patients with PD diagnosed with cold‐dampness congealing pattern were randomly assigned in a ratio of 1:1 to receive PN or TN at bilateral SP 6 for 10 min. Acupuncture was performed when the menstrual pain score was over 40 mm on the first day of menstruation, as measured using the visual analog scale for pain (VAS‐P). The primary outcome was average menstrual pain (VAS‐P). Secondary outcomes included the pulsatility index (PI), resistance index (RI), and systolic‐diastolic peaks ratio (S/D) in uterine arteries as measured using color Doppler ultrasonography; anxiety as assessed using the Hamilton Anxiety Rating Scale (HAMA), blood pressure (BP), and heart rate (HR). Results: Forty‐eight patients completed the study. The TN group exhibited a significant reduction in VAS‐P scores (–5.71 mm, 95% confidence interval (CI): –8.78, –2.63, P = .001), RI values (–0.05, 95% CI: –0.09, –0.01, P = .015), and HAMA values (–2.50, 95% CI: –4.78, –0.22, P = .032) when compared with the PN group. No significant differences in PI, S/D, BP, or HR values were observed between the two groups (P > .05). Conclusion: TN at SP 6 was superior to PN in alleviating menstrual pain and anxiety in patients with PD. This analgesic effect of TN may be due to its better ability to improve uterine arterial blood flow via decreases in RI values.

Mohammadi, F., et al. (2021). "The effect of pregnancy training classes based on bandura self-efficacy theory on postpartum depression and anxiety and type of delivery." Journal of education and health promotion 10: 273.
	BACKGROUND: Postpartum depression and anxiety is one of the most common complications that women face and cause many problems for mother, baby, and family. Considering the effect of self-efficacy on women's adaptation to pregnancy and delivery conditions and their mental health during this period, the present study was designed to investigate the effect of pregnancy training classes based on Bandura self-efficacy theory on postpartum depression and anxiety and type of delivery. MATERIALS AND METHODS: In this clinical trial study, 64 pregnant women were randomly divided into intervention and control groups. Mothers in the intervention group received pregnancy training in eight sessions (each session was 2-hour) from the 20th week of pregnancy. The classes were run by a trained midwife and the content of the training was based on Bandura self-efficacy components. The mothers in the control group received routine care. The demographic-reproductive information form, Beck Depression and Spielberger Anxiety Questionnaire were completed by pregnant women of both groups at several times, before the program, 1 week and 1 month after delivery. RESULTS: The results showed that the training program significantly decreased the depression score in 1 week and 1 month after delivery in the intervention group compared to the control group. In addition, this training program decreased the mean score of apparent and hidden anxiety in the intervention group 1 month after delivery, although this decrease was not statistically significant. Furthermore, 80.55% of the intervention group and 58.33% of the control group had vaginal delivery, which were significantly different between the two groups in terms of the type of delivery. CONCLUSION: The findings showed that pregnancy training classes based on Bandura self-efficacy theory decrease depression and anxiety and increases vaginal delivery rate.

Mohammadi, M., et al. (2020). "Assisted reproductive technology and the risk of gestational diabetes mellitus: a systematic review and meta-analysis." Middle East Fertility Society Journal 25(1): 6.
	Background: The use of assisted reproductive technology (ART) is increasing worldwide, and observational studies have indicated that women who conceived by ART have an increased risk of pregnancy complications including gestational diabetes mellitus (GDM). We aimed to determine the risk of GDM among women who conceived with ART by systematic review and meta-analysis. Main text: A systematic literature search was conducted in ISI Web of Knowledge, MEDLINE, Scopus, and Embase through May 2017 for English-language articles using a list of keywords. All studies comparing GDM in women conceived by ART and those who conceived spontaneously were included. Data extraction was performed by two authors independently and discrepancies were resolved by discussion. In total, 48 studies with 91,487 pregnancies conceived through ART and 2,525,234 spontaneously conceived met the inclusion criteria. There was evidence of substantial heterogeneity among these studies (P < 0.001, I2 = 98.6%). Random effects meta-analysis showed a significant increase in GDM among those who conceived by ART compared with those who conceived spontaneously (pooled relative risk = 1.51, 95% confidence interval = 1.18-1.93). Visual inspection of the funnel plot did not reveal any publication bias, which was supported by Egger's test and Begg's test. Conclusion(s): The findings of this systematic review indicate that the use of ART treatment is associated with a 1.51-fold increase in GDM. Women need to be counselled carefully before undergoing ART treatment about the possibility and risk of GDM.Copyright © 2020, The Author(s).

Mohammadi Mohammad, M., et al. (2022). "Effect of omega-3 fatty acids on premenstrual syndrome: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 48(6): 1293-1305.
	Introduction: To date, no definitive results have been reported on the effect of omega-3 fatty acids on premenstrual syndrome (PMS). Therefore, this systematic review and meta-analysis aimed to determine the effect of omega-3 fatty acids on PMS.; Methods: In this systematic review and meta-analysis, the databases were searched. In this regard, randomized clinical trials investigating the effect of omega-3 fatty acids on PMS were included. The quality of the studies was assessed using the Cochrane Collaboration's Risk of Bias tool. Meta-analysis was done based on random effects model and calculation of standardized mean difference (SMDs).; Results: The results of meta-analysis showed that omega-3 fatty acids were efficient in reducing the severity of PMS in women (SMD = -0.968, 95% confidence interval [CI]: -1.471 to -0.464). In addition, the results showed that the studies were heterogeneous (I 2 = 89.11%, p <0.001). Based on meta-regression analysis, aging (β = -0.150, 95% CI -0.202 to -0.098, p <0.001) and increasing the duration of intervention (β = -0.579, 95% CI -0.781 to -0.378, p <0.001) had a significant effect on the severity of PMS. We also found that omega-3 fatty acids could significantly reduce the somatic (SMD = -0.800, 95% CI: -1.126 to -0.474) and psychological (SMD = -0.373, 95% CI: -0.686 to -0.061) symptoms of PMS.; Conclusion: Omega-3 fatty acids could reduce the severity of PMS. However, we should caution in the conclusion in affirming the beneficial effects of n-3 PUFAs on PMS, since the heterogeneity is evident in the analysis. The efficacy of the treatment was enhanced by increase of the treatment duration. (© 2022 Japan Society of Obstetrics and Gynecology.)

Mohammadi, S., et al. (2023). "Effects of eight-week high-intensity interval training on some metabolic, hormonal and cardiovascular indices in women with PCOS: a randomized controlled trail." BMC sports science, medicine & rehabilitation 15(1): 47.
	Background: Studies have revealed that high-intensity interval training (HIIT) has beneficial effect on hormonal, cardiovascular indices in women with polycystic ovary syndrome (PCOS). There, however, is still no comprehensive data on the type, intensity and duration of training for these women.; Objective: The current study aimed to investigate the effects of high-intensity interval training (HIIT) on metabolic, hormonal and cardiovascular indices in women with PCOS compared to a control group.; Methods: In a randomized controlled study, 28 patients (age: 23.8 ± 5.3 years, weight: 82.4 ± 9.7 kg, BMI: 30.33 ± 3.99 kg/m 2 ) were divided into two groups including HIIT (n = 14) and the control (n = 14). The training protocol was performed with 100-110 maximum aerobic velocity (MAV), 4-6 sets, 4 laps, 3 sessions per week for eight weeks. Anthropometric indices, aerobic performance, insulin resistance and sensitivity, lipid profiles, testosterone, cortisol and hs-CRP were evaluated.; Results: The HIIT intervention decreased BMI, waist to hip ratio (WHR), visceral fat, insulin, insulin resistance, low density lipoprotein (LDL), atherogenic index, cholesterol and cortisol (P < 0.05). All variables remained unchanged in the control group (P > 0.05). Except for VAI, FBG, HDL, TG and AIP, the rest of the variables in the training and control groups show a significant difference (P < 0.05).; Conclusion: The results of the present study indicate that eight weeks of HIIT has beneficial effects on anthropometric, insulin sensitivity, fat profile, and inflammatory and cardiovascular indices in PCOS patients. It seems that the intensity of HIIT (100-110 MAV) is a determining factor in creating optimal adaptations in PCOS patients.; Trail Registration: IRCT20130812014333N143. Registration date: 22/03/2020. URL: https://en.irct.ir/trial/46295 . (© 2023. The Author(s).)

Mohammadpour, M., et al. (2022). "Effect of counselling with men on perceived stress and social support of their pregnant wives." Journal of Reproductive and Infant Psychology 40(2): 118-132.
	Background: Given the important role of spouses during pregnancy, this study aimed to determine the effect of counseling with men on stress and social support of their women (primary outcomes), anxiety, depression, weight gain, newborns' anthropometric indicators, frequency of cesarean section and preterm delivery (secondary outcomes).; Methods: 102 pregnant women were randomly assigned to two groups of counseling and control. Four sessions of counseling were held for the spouses of intervention group. Perceived Personal Resource Questionnaire-85-Part2, Perceived Stress Scale, Edinburgh's Postpartum Depression Scale, and Spielberger's State and Trait Anxiety Inventory were completed before and four weeks after intervention. The participants were followed up until delivery, and newborns' anthropometric indicators, delivery type, and preterm delivery were recorded.; Results: The mean score of social support increased significantly 4 weeks after intervention in the counseling group compared to the control group (MD:12.7; 95%CI: 18.5 to 6.9). There was no significant difference between groups in the mean score of stress, anxiety, depression, and weight gain during pregnancy at four weeks after intervention and also frequency of cesarean delivery, preterm delivery, and anthropometric indicators of newborns ( p >0.05).; Conclusions: Counseling with fathers can be recommended as an effective intervention to increase social support of pregnant women.; Trial Registration: IRCT2017042910324N38. Registered 25 June 2017, http://en.irct.ir/trial/10813.

Mohammed Walid, E., et al. (2022). "Sildenafil citrate as an adjuvant to clomiphene citrate for ovulation induction in polycystic ovary syndrome: crossover randomized controlled trial." Przeglad menopauzalny = Menopause review 21(1): 20-26.
	Introduction: To evaluate sildenafil citrate as an adjuvant to clomiphene citrate (CC) for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS).; Material and Methods: A total of 595 infertile PCOS women were randomly assigned into either clomiphene/sildenafil (C/S) group or CC group. Transvaginal (TVS)-Doppler studies were done for participants when the dominant follicle reach 16 mm, to measure the resistance index, pulsatility index, and maximum velocity of sub-endometrial, uterine, and ovarian vessels. Participants were examined using TVS on the 21 st day of the cycle to detect ovulation or, after a positive pregnancy test, for documentation of pregnancy. Participants with negative pregnancy tests were given 2 months' rest without OI, followed by crossover of OI medication between the 2 studied groups. The crossover results were assessed by TVS, TVS-Doppler, and pregnancy test.; Results: The endometrial thickness was significantly higher among the C/S than the CC group during the first 3 months (9.6 ±1.2 vs. 8.7 ±1.0 mm, respectively, p = 0.003) and after crossover of OI (9.1 ±1.3 vs. 8.2 ±1.0 mm, respectively, p = 0.007).The chemical and clinical pregnancy rates were significantly higher among the C/S compared to the CC group (39.8% and 36.6% vs. 25% and 18.98%, respectively) ( p = 0.01 and 0.001, respectively) during the first 3 months and after crossover of OI (36.6% and 33.1% vs. 23.8% and 20.6%, respectively) ( p = 0.02 and 0.01, respectively).; Conclusions: SC as an adjuvant to CC for OI in PCOS women increases the chemical and clinical pregnancy rates. It also improves the endometrial thickness and ovulation rate through improved endometrial and ovarian Doppler indices.; Competing Interests: The authors report no conflicts of interest. (Copyright © 2022 Termedia.)

Mohan, G. and S. Chattopadhyay (2020). "Cost-effectiveness of Leveraging Social Determinants of Health to Improve Breast, Cervical, and Colorectal Cancer Screening: A Systematic Review." JAMA Oncology 6(9): 1434-1444.
	Importance: Screening for breast, cervical, and colorectal cancers in the United States has remained below the Healthy People 2020 goals, with evidence indicating that persistent screening disparities still exist. The US Department of Health and Human Services has emphasized cross-sectoral collaboration in aligning social determinants of health with public health and medical services. Examining the economics of intervening through these novel methods in the realm of cancer screening can inform program planners, health care providers, implementers, and policy makers.; Objective: To conduct a systematic review of economic evaluations of interventions leveraging social determinants of health to improve screening for breast, cervical, and colorectal cancer to guide implementation.; Evidence Review: A systematic literature search for economic evidence was performed in MEDLINE, Embase, PsycINFO, Cochrane Library, Global Health, Scopus, Academic Search Complete, Business Source Complete, EconLit, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ERIC (Education Resources Information Center), and Sociological Abstracts from January 1, 2004, to November 25, 2019. Included studies intervened on social determinants of health to improve breast, cervical, and colorectal cancer screening in the United States and reported intervention cost, incremental cost per additional person screened, and/or incremental cost per quality-adjusted life-year (QALY). Risk of bias was assessed along with qualitative assessment of quality to ensure complete reporting of economic measures, data sources, and analytic methods. In addition, included studies with modeled outcomes had to define structural elements and sources for input parameters, distinguish between programmatic and literature-derived data, and assess uncertainty.; Findings: Thirty unique articles with 94 706 real and 4.21 million simulated participants satisfied our inclusion criteria and were included in the analysis. The median intervention cost per participant was $123.87 (interquartile interval [IQI], $24.44-$313.19; 34 estimates). The median incremental cost per additional person screened was $250.37 (IQI, $44.67-$609.38; 17 estimates). Studies that modeled final economic outcomes had a median incremental cost per person of $122.96 (IQI, $46.96-$124.80; 5 estimates), a median incremental screening rate of 15% (IQI, 14%-20%; 5 estimates), and a median incremental QALY per person of 0.04 years (IQI, 0.006-0.06 year; 5 estimates). The median incremental cost per QALY gained of $3120.00 (IQI, $782.59-$33 600.00; 5 estimates) was lower than $50 000, an established, conservative threshold of cost-effectiveness.; Conclusions and Relevance: Interventions focused on social determinants of health to improve breast, cervical, and colorectal cancer screening appear to be cost-effective for underserved, vulnerable populations in the United States. The increased screening rates were associated with earlier diagnosis and treatment and in improved health outcomes with significant gains in QALYs. These findings represent the latest economic evidence to guide implementation of these interventions, which serve the dual purpose of enhancing health equity and economic efficiency.

Mohanasundharam, M., et al. (2022). "Current Pharmacotherapeutic Approach to the Management of Polycystic Ovary Syndrome." Journal of Pharmaceutical Negative Results 13: 1365-1374.
	Purpose: Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and the treatment aims to correct the menstrual cycle, excess androgen characteristics such as hirsutism, acne, and alopecia and increase the pregnancy rates in patients who are planning to conceive. The objective of this review is to provide an overall view on the currently available treatment options for PCOS. Method(s): A comprehensive literature search was conducted in the database using MEDLINE, PUBMED, SCIENCE DIRECT, SPRINGER LINK, EMBASE, OVID and SCOPUS Findings: The results of this review showed a wide range of therapeutic options that improves the overall life style of the PCOS patient. The proposed mechanism of PCOS include hypothalamic abnormal gonadotrophic releasing hormone pulsatile secretion, excess of luteinizing hormone, increased ovarian or adrenal androgen production, cortisol increased catabolism, and abnormalities in insulin production or action. Implications: The current available therapeutic options include estrogen receptor modulators, insulin sensitizing agents, aromatase inhibitors, gonadotropins, combined oral contraceptives and anti-androgens which provides a successful improvement in the clinical presentation of the patient interfering with one or more mechanisms of PCOS.Copyright © 2022 Authors. All rights reserved.

Mohapatra, K. C., et al. (2021). "Laparoscopic Versus Open Rectopexy for Rectal Prolapse: A Randomized Controlled Trial." Cureus 13(3): e14175.
	Introduction Most of the patients with rectal prolapse complain of fecal incontinence followed by constipation. Surgery is the only definitive treatment option for rectal prolapse. There are two approaches: either transanal/perineal or transabdominal. The abdominal procedures can be done in the open laparotomy method or laparoscopically. Suture rectopexy is a very old and popular method of treating rectal prolapse. Nowadays, rectopexy by laparoscopic approach is considered the gold standard treatment for rectal prolapse. The study has been conducted to compare both the procedures and their outcomes in terms of conditions associated with rectal prolapse. Methods All consecutive patients with full-thickness rectal prolapse who had attended the surgery outpatient department were included in the study. The patients had undergone either open suture rectopexy or laparoscopic rectopexy after randomization. Assessment of postoperative pain, mean days of hospital stay, constipation, and incontinence score along with operative time, recurrence within six months of follow-up, and time to resume bowel activity were done. The patients were followed up for 18 months at regular intervals. Results A total of 58 patients were included in the study: 27 in the open group and 31 in the laparoscopic group. The operative time was 102 minutes versus 129 minutes (p=0.0001) in the open and laparoscopic groups, respectively. The laparoscopic group had an earlier resumption of bowel activity (3.1 days vs. 1.4 days [p=0.0001]); fewer days of hospital stay (6.8 days vs. 2.5 days [p=0.0001]), less postoperative pain (mean visual analogue scale score for pain on postoperative day one 4.0 versus 3.1 [p=0.0035] and on postoperative day two 3.8 versus 2.2 [p=0.0001]). There was no significant difference in postoperative constipation score and incontinence score between the two groups. Conclusion Laparoscopic rectopexy results in lesser postoperative pain, lesser hospital stay, and better patient satisfaction than open rectopexy.

Mohd, F., et al. (2022). "Twenty-first century oocyte cryopreservation-in vitro maturation of immature oocytes from ovarian tissue cryopreservation in cancer patients: A systematic review." Women's health (London, England) 18: 17455057221114269.
	Objectives: Our review aimed to consolidate the latest update on the application of in vitro maturation among immature oocyte harvest in combination with ovarian tissue cryopreservation known as ovarian tissue oocyte-in vitro maturation.; Methods: A thorough search for relevant studies was conducted via PubMed, Google Scholar, EMBASE, and clinical.gov databases up to December 2020. The primary outcome was the oocyte maturation rate, which measured the number of immature oocytes (geminal vesicle stage) that progressed to mature oocytes (meiosis II stage) following in vitro maturation. The secondary outcomes were the fertilization rate following intracytoplasmic sperm injection/in vitro fertilization of these oocytes for the embryo cryopreservation cohort. Our review included pre-pubertal girls and women with cancer who underwent ovarian tissue oocyte-in vitro maturation as fertility preservation.; Results: The primary search identified 207 studies. Twelve manuscripts were selected for inclusion in our review following duplication assessment, title and abstract screening, and full-text evaluation tailored to our inclusion criteria. All the population belonged to a cancer group and underwent concurrent ovarian tissue oocyte-in vitro maturation. A total of 5724 immature oocytes were obtained following ovarian tissue cryopreservation. Approximately 33.84% of the immature oocytes successfully matured via in vitro maturation, which were cryopreserved as oocytes or fertilized as embryos and subsequently stored for future use.; Conclusion: Our review proposed the potential application of ovarian tissue oocyte-in vitro maturation in increasing the number of mature oocytes. The acceptable improvement in oocyte maturation rate following in vitro maturation indicates that improving oocyte outcomes is an excellent cost-effective strategy for fertility preservation among women with cancer.

Mohd Falihin, M., et al. (2021). "Effects of L-carnitine supplementation for patients with polycystic ovarian syndrome." PROSPERO International prospective register of systematic reviews.
	
Mohd, N., et al. (2022). "The efficacy and safety of anti-PD-1/PD-L1 immunotherapy in endometrial cancer: a systematic review and meta-analysis."
	
Mohd, N., et al. (2022). "Effect of Acupressure at P6 on Nausea and Vomiting in Women with Hyperemesis Gravidarum: a Randomized Controlled Trial." International Journal of Environmental Research and Public Health 19(17).
	Hyperemesis gravidarum is characterized by severe nausea and vomiting. This study aims to illustrate the efficacy of acupressure at P6 in treating nausea and vomiting in hyperemesis gravidarum. This parallel randomized controlled trial was conducted from 2016‐2017 in a tertiary hospital. Hospitalized women with ≤16 weeks of gestation and moderate to severe nausea and vomiting classified using a modified PUQE score were randomly assigned in a 1:1 ratio to either apply an acupressure wristband at the P6 point three times daily or to receive regular doses of intravenous antiemetics. The primary outcome was differences in modified PUQE scores among the groups. The secondary outcomes were differences in the rate of urine ketone clearance and the frequency of requiring rescue antiemetics. Ninety women were equally randomized into two groups, with no dropout. There was a statistically significant difference in the degrees of nausea and vomiting between the groups at 8, 16, and 24 hours post‐admission (p8hours= 0.001, p16hours = 0.006, and p24hours = 0.001). The requirement of antiemetics and the rate of urine ketone clearance between the two groups were also statistically significant, at p = 0.001 and p = 0.02 respectively. There were no side effects in either group. The P6 acupressure was efficacious in alleviating nausea and vomiting among hyperemesis gravidarum women. The trial was retrospectively registered on ClinicalTrials.gov (NCT05175079).

Mohd, S., et al. (2022). "Effects of L-carnitine supplementation for women with polycystic ovary syndrome: a systematic review and meta-analysis." PeerJ 10: e13992.
	Background: Polycystic ovary syndrome (PCOS) is a disorder in reproductive age women and is characterized by hyperandrogenic anovulation and oligo-amenorrhea, which leads to infertility. Anovulation in PCOS is associated with low follicle-stimulating hormone levels and the arrest of antral follicle development in the final stages of maturation. L-carnitine (LC) plays a role in fatty acid metabolism, which is found to be lacking in PCOS patients. This systematic review and meta-analysis aimed to determine the effectiveness of LC supplementation for patients with PCOS.; Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychological Information Database (PsycINFO), and the World Health Organization International Clinical Trials Registry Platform for all randomized control trials, comparing LC alone or in combination with other standard treatments for the treatment of PCOS from inception till June 2021. We independently screened titles and abstracts to identify available trials, and complete texts of the trials were checked for eligibility. Data on the methods, interventions, outcomes, and risk of bias from the included trials were independently extracted by the authors. The estimation of risk ratios and mean differences with a 95 percent confidence interval (CI) was performed using a random-effects model.; Results: Nine studies with 995 participants were included in this review. Five comparison groups were involved. In one comparison group, LC reduced the fasting plasma glucose (FPG) (mean differences (MD) -5.10, 95% CI [-6.25 to -3.95]; P = 0.00001), serum low-density lipoprotein (LDL) (MD -25.00, 95% CI [-27.93 to -22.07]; P = 0.00001), serum total cholesterol (MD -21.00, 95% CI [-24.14 to -17.86]; P = 0.00001), and serum triglyceride (TG) (MD -9.00, 95% CI [-11.46 to -6.54]; P = 0.00001) with moderate certainty of evidence. Another comparison group demonstrated that LC lowers the LDL (MD -12.00, 95% CI [-15.80 to -8.20]; P = 0.00001), serum total cholesterol (MD -24.00, 95% CI [-27.61 to -20.39]; P = 0.00001), and serum TG (MD -19.00, 95% CI [-22.79 to -15.21]; P = 0.00001) with moderate certainty of evidence.; Conclusion: There was low to moderate certainty of evidence that LC improves Body Mass Index (BMI) and serum LDL, TG, and total cholesterol levels in women with PCOS.; Competing Interests: Norhayati Mohd Noor is an Academic Editor for PeerJ. (©2022 Mohd Shukri et al.)

Mohiuddin, M., et al. (2021). "Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis." Pain medicine (Malden, Mass.) 22(12): 2896-2907.
	Objective: To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain.; Methods: A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis.; Results: Nine studies (n = 863) were included (five randomized controlled trials [RCTs], two open-label non-comparative studies and two comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of three RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% confidence interval [CI]: -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI: -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain.; Conclusions: While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine's role, if any, in pain medicine. (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mohr-Sasson, A., et al. (2022). "Placenta accreta spectrum in subsequent pregnancy following myomectomy." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(22): 4332-4337.
	Purpose: To compare the prevalence of placental abnormalities in pregnancy following different modes of operative myomectomy.; Methods: A retrospective cohort study, including all women after myomectomy that gave birth in a single tertiary care center from February 2011 to January 2019. Data was collected from the patients' medical files and completed by telephone questionnaire. Patients were stratified to 3 groups, according to the mode of operative myomectomy (laparotomy, laparoscopy, hysteroscopy). Groups were compared for women demographics, fibroid's characteristics, operative management, post-operative placental evaluation and delivery characteristics. Primary outcome was defined as the need for any intervention for placental separation during the third phase of the delivery.; Results: Two hundred forty one women met inclusion criteria. Complete follow-up was achieved in 199 (82.57%) women, of whom 82, 89, and 28 underwent laparoscopic, laparotomy and hysteroscopic myomectomy, respectively. There were no in-between groups differences in women's age, BMI, and gravidity. Disruption of the endometrial cavity during laparoscopy and laparotomy was reported in 3 (3.6%) and 7 (7.8%) cases, respectively ( p = .21). During the subsequent pregnancy following myomectomy, placenta accreta spectrum disorder was suspected in only one woman in each of the study groups ( p = .63). Placenta previa was low and comparable between groups. Vaginal delivery rate was significantly higher in the hysteroscopy group, as compared to the laparoscopy or the laparotomy groups [11 (36.3%) vs. 5 (6.1%) vs. 4 (4.5%); p = .001], with significantly lower need for manual lysis of the placenta [11(39.0%) vs. 51 (62.1%) vs. 62 (69.7%); p = .01] and further interventions for blood loss control.; Conclusions: Subsequent pregnancy following surgical myomectomy was not found to be associated with higher prevalence placental abnormality. Furthermore, other than manual lysis, the different modes of myomectomy did not necessitate any further intervention for complications associated with abnormal placentation requiring intervention.; Key Message: Subsequent pregnancy following surgical myomectomy is not associated with higher prevalence of placental abnormality.

Mohsen, S., et al. (2023). "Comparison of classic and direct approach for sacrospinous ligament fixation with vaginal hysterectomy." Ginekologia i poloznictwo 18(1): 1‐4.
	Purpose: Two techniques of (SSLF) in the terms of intraoperative parameters (time, complications) and 1‐year anatomic outcomes and symptoms in patients who presented with stage 3 or 4 pelvic organ prolapse and undergoing vaginal hysterectomy. Method: Thisstudyincluded60patients,dividedinto 2groups:Group 1: willundergoSSLF intheclassicwayincluded 32patients.Group2: will undergoSSLF with direct approachincluded 28 patients. Bothgroups will be compared in the terms of intraoperative parameters (time, complications)and1‐year anatomic outcomes. Results: There was a significantdifferenceinthe operatingtime, and associated bleeding between the 2 groups, being less in the second group. However, no significant difference in the rate of complications in both. Conclusion: This modifieddirectapproachhas the advantageofshorter operative time and less bleeding than the classic method including post vaginal wall dissection and has the same short term results as the classicmethod canbe usedwhen thespecialized instrument forsuture placementarenotavailable.

Mohseni, M., et al. (2024). "Efficacy of N-acetylcysteine as Add-on Therapy for the Management of Chronic Pelvic Pain Syndrome in Women." Current Women's Health Reviews 20(1).
	Objective: Considering supportive evidence on N‐acetylcysteine (NAC) effectiveness in neuropathic pain syndromes, we conducted this study to evaluate its effect on women suffering from chronic pelvic pain syndrome (CPPS). Methods: In a randomized, double‐blind study, 106 women with CPPS were assigned to receive NAC+amitriptyline or placebo+amitriptyline treatment. Amitriptyline was administrated at a dose of 25 mg/daily and NAC and placebo at 600 mg twice daily. The effect of treatment was assessed on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI) and its domain scores, including pain, urinary symptoms, and quality of life impact scores at weeks 4 and 8 after treatment. The global response was also assessed on the 7‐point patient‐reported global response assessment (GRA) scale at the end of the study. Results: By week 4, comparative improvements were noticed in the two groups' NIH‐CPSI total score and domain scores. From week 4 to week 8, we noted the superior efficacy of NAC+amitriptyline treatment over placebo+amitriptyline in improving the NIH‐CPSI total score and its domain scores, as the proportion of patients responding to treatment (the subjects with ≥ 6‐point reduction in the total NIH‐CPSI score), as well those reporting marked or moderate improvements in their overall symptoms on GRA was significantly more significant in patients receiving NAC+amitriptyline treatment relative to those receiving placebo+amitriptyline treatment. Conclusion: These findings provided preliminary evidence regarding the possible role of NAC as an adjunct therapy in the management of CPPS in women, which needs to be validated in future studies.

Mohseni, S., et al. (2022). "Effect of vitamins C and E on cancer survival; a systematic review." DARU, Journal of Pharmaceutical Sciences 30(2): 427-441.
	Purpose: Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival. Method(s): Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies. Result(s): We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp. Conclusion(s): Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm. PROSPERO Registration number: CRD42020152795. Graphical abstract: [Figure not available: see fulltext.]Copyright © 2022, The Author(s), under exclusive licence to Tehran University of Medical Sciences.

Mohseni, S., et al. (2021). "Targeting dyslipidemia with antioxidative vitamins C, D, and E; a systematic review of meta-analysis studies: Dyslipidemia and antioxidative vitamins." Journal of Diabetes and Metabolic Disorders 20(2): 2037-2047.
	Background: There is controversial evidence for the beneficial effects of antioxidative vitamins (vits) on dyslipidemia. In this regard, we aimed to systematically review all meta-analyses of trials on this topic.; Methods: We comprehensively searched PubMed, Web of Science, Scopus, and Cochrane Library databases until January 2021 to explore the published English meta-analyses of trials conducted to assess the effects of single or combined vits C, D and E consumption on lipid profile. The meta-analyses of observational, in vivo/in vitro , or case-report studies were excluded. Search results were reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flowchart.; Results: Overall, 25 meta-analyses including 32,177 individuals with different underlying disorders met our inclusion criteria. Numerous studies had assessed supplementation with Vit-D or its combination with other agents on lipid profile. Consumption of 400 IU/day (d) to 50,000 IU/week (w) Vit-D for at least eight weeks improved the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in type 2 diabetes mellitus or polycystic ovary syndrome (PCOS) patients. This treatment reduced the levels of TC and TG in patients with chronic kidney disease. A significant increase in high-density lipoprotein cholesterol (HDL-C) levels was only observed in coronary artery disease patients. Sole intake of 500-2000 mg/d Vit-C for at least 3 weeks improved LDL-C and TG values in hypercholesterolemic patients. Nevertheless, sole intake of Vit-E had controversial effects on lipid profile. The combination of 400-1800 IU/d omega-3 free fatty acid (FFA) and 400 IU/d Vit-E significantly reduced the levels of LDL-C and TG in overweight individuals, without any significant effect on other components. A significant improvement of TG values was observed after consumption of 1000-2000 mg/d omega-3 FFA plus 400 IU/d Vit-E along with 50,000 IU/each 2w Vit-D for at least 6 weeks in diabetic patients.; Conclusion: The beneficial effects of antioxidative vitamins (C, D, E) or their combination with other agents on lipid profile varied based on their dosage, intake duration, and the health status of the individuals.; Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-021-00919-8.; Competing Interests: Competing interestAll authors declare that there are no conflicts of interest. (© Springer Nature Switzerland AG 2021.)

Mohtashami, S., et al. (2024). "Efficacy of Ethanol Sclerotherapy Versus Laparoscopic Excision in the Treatment of Ovarian Endometrioma." Journal of Obstetrics and Gynecology of India 74(1): 60-66.
	Objective: The purpose of this study was to examine the recurrence rates of ovarian endometrioma, dysmenorrhea, dyspareunia, and related complications between sclerotherapy and laparoscopic ovarian cystectomy in individuals aged 25 to 38. Method(s): Eighty-eight women participated in this retrospective, single-center study between January 2020 and February 2022. Patients received either laparoscopy or sclerotherapy, depending on the opinion of the pertinent physician. In this study, the following parameters were retrospectively analyzed in follow-up visits 2, 6 and 12 months after sclerotherapy and laparoscopy: dysmenorrhea and dyspareunia by visual analog scale, complications following the intervention, and serial pelvic sonograms for endometrioma cyst recurrence. Moreover, serum Anti-Mullerian hormone (AMH) level before and 6 months after sclerotherapy/surgery were analyzed. The collected data were then analyzed using R software. Result(s): The results demonstrate the efficiency of both sclerotherapy and laparoscopic techniques in reducing endometrioma-related dysmenorrhea and dyspareunia over a 12-month period. There was no statistically significant difference in the occurrence of complications and recurrence rate between these two therapies, and both are equally beneficial. Also, the rate of AMH decline after laparoscopy was higher than sclerotherapy; however there was not a statistically significant change in serum level of AMH in laparoscopy compared to the sclerotherapy after 6 months. Conclusion(s): Considering all the data, it appears that sclerotherapy, with its lower cost, shorter hospital stay, and quicker return to activities, can be a laparoscopic alternative to endometrioma cyst removal. More studies are required.Copyright © Federation of Obstetric & Gynecological Societies of India 2024.

Moini, A., et al. (2022). "Subcutaneous progesterone (Prolutex) versus vaginal (Cyclogest) for luteal phase support in IVF/ICSI cycles: a randomized controlled clinical trial." Middle East Fertility Society Journal 27(1): 16.
	Background: To compare the safety, efficacy, and tolerability of subcutaneous vaginal progesterone suppository for luteal phase support (LPS) in assisted reproduction technology (ART) cycles in patients referred to the Royan Institute. Method(s): This randomized clinical trial was conducted from August 2016 to March 2018. The infertile patients undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were evaluated. The controlled ovarian stimulation (COH) was performed in all of the patients with standard long GnRH agonist protocol. After ovum pickup, eligible women were randomly allocated into two groups. In group A, since oocyte retrieval day, subcutaneous injections of progesterone (50 mg) (Prolutex) were used daily, and in group B, two vaginal suppositories (Cyclogest ) were administrated for LPS. The clinical pregnancy and miscarriage rates and the drug's side effect were compared between two groups by appropriate statistical tests. Result(s): Finally, 40 patients in each group were enrolled, and the IVF/ICSI outcomes were compared between groups. The data analysis showed that no significant differences were found between groups in terms of the demographic, infertility characteristics, and the COH outcome between groups. The chemical and clinical pregnancy rates (CPR) in group A were significantly higher than those of group B (P = 0.04, P = 0.02, respectively). The implantation and twin pregnancy rates in group B were significantly higher than those in group A (P = 0.009, P = 0.02, respectively). Conclusion(s): The subcutaneous administration of progesterone 25 mg twice daily for LPS was associated with higher CPR versus vaginal progesterone, and it was safe and well-tolerated in the follow-up. In addition, it can be a suitable replacement in cases of allergic reactions to vaginal suppositories. However, further study is required to compare the cost-effectiveness of these medications. Trial registration: The study was also registered in the Iranian Registry of Clinical Trials on February 19, 2015 (IRCT201402191141N18 at www.irct.ir, registered prospectively).Copyright © 2022, The Author(s).

Moini, A., et al. (2021). "The effect of acetylsalicylic acid on pain and recurrence of endometriosis after surgery: a randomized controlled trial." Journal of Endometriosis and Pelvic Pain Disorders 13(4): 288‐292.
	Background: Reactive oxygen species (ROS) might increase growth and adhesion of endometrial cells in the peritoneal cavity, and lead to endometriosis. In this study the we evaluate the effect of an antioxidant, acetylsalicylic acid (aspirin), to determine whether aspirin administration to patients with endometriosis would affect pelvic pain and disease recurrence. Material and methods: This randomized controlled trial was conducted from March 2018 to March 2020 on women, 19 to 40 years of age, who were diagnosed with endometriosis after undergoing laparoscopic surgery. Study participants were randomly assigned to one of two groups, Oral contraceptive pills (OCP) and placebo or OCP and aspirin, which were administered daily for 6 months. Pelvic pain, dysmenorrhea, mass size, and menstrual bleeding were evaluated at 3 and 6 months. Results: There were 38 patients in the aspirin group and 49 participants in the placebo group. The mean dysmenorrhea Visual analog scale (VAS) score after 3 months was 2.24 in the aspirin group and 3.61 in the placebo group. After 6 months, the dysmenorrhea VAS scores were 0.68 (aspirin group) and 2.69 (placebo group) (p = 0.005 and p = 0.00, respectively). Dyspareunia and pelvic pain showed significant reductions (p = 0.00). Six patients in the control group and four patients in the aspirin group experienced lesion recurrence (p = 0.45). Conclusion: The results suggest that aspirin, as an antioxidant, could effectively reduce pain in women with endometriosis. However, additional studies that enroll larger numbers of participants and long‐term follow up will enable better evaluation of recurrence.

Moini, A., et al. (2022). "The Influence of Different Endometrium Preparation Regimen for Frozen Thawed Embryo Transfer on Perinatal Outcomes of Singletons Pregnancy in Patients with Polycystic Ovary Syndrome: A Randomized Controlled Trial." Journal of Pharmaceutical Negative Results 13: 5220-5228.
	Introduction: According to the lack of strong evidence, whether the different frozen thawed embryo transfer (FET) protocols in patients with polycystic ovarian syndrome (PCOS) have any effect on its success is still unclear. This study was performed to compare the effect of hormone replacement treatment (HRT) protocols and gonadotropin-releasing hormone GnRH agonist (GnRHa)-HRT protocols on perinatal outcomes of singletons pregnancy in patients with PCOS. Material(s) and Method(s): The study design was a randomized controlled trial (RCT) conducted at a tertiary referral hospital. A total of 132 patients with PCOS undergoing FET cycles were included in this study. The patients were randomly divided into two groups according to a computer-generated method. The GnRHa-HRT group (n = 66) had pituitary suppression before steroid hormone administration whereas HRT group (n = 66) commenced steroid supplementation without prior pituitary desensitization. Primary outcome was considered birthweight of singleton newborns. Result(s): There were no differences in birth weight of newborns between two groups (p=0.50). No significant differences were found between two groups for preeclampsia, gestational diabetes mellitus, IUGR, first trimester bleeding, and preterm labour. Moreover, neonatal anomalies were not significantly different between two groups, but no neonatal anomalies were reported from group HRT. Conclusion(s): The findings indicated that neonatal birth weight and other prenatal outcome were not significantly different between two groups. It seems that the use of GnRH agonist creates additional burdens and adverse events for the patient, and the use of estradiol alone is an effective, less complicated and economically cost-effective protocol for patients with PCOS.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Moini, A., et al. (2022). "The effect of hydroxychloroquine on pregnancy outcomes in patients with unexplained recurrent pregnancy loss: a placebo-controlled study "pilot study"." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(8): 3471-3476.
	This double-blind placebo-controlled study investigated the effect of hydroxychloroquine on pregnancy outcomes in people with unexplained recurrent pregnancy loss (URPL). The inclusion criteria included gestational age ≤6 weeks and a history of at least two miscarriages. The exclusion criteria included any known cause for previous abortions or a history of any chronic diseases. Participants were given 200 mg hydroxychloroquine or placebo twice a day until gestational week 20. Twenty-nine women were enrolled. There was no statistically significant difference between the two groups in terms of age, BMI, gravidity, previous abortion, relative married couple, and infertility. Miscarriage occurred in five women including one in the hydroxychloroquine group (7.69%) and four women in the placebo group (28.57%) (OR: 2.36, 95% PL CI:1.07, 8.93). However, after adjusting for potential confounders, there was no significant difference between the two groups (aOR: 2.96, 95%CI: 0.91, 10.02).IMPACT STATEMENT What is already known on this subject? Miscarriage, a prevalent concern in the field reproductive medicine, causes psychological and family problems for couples. Unfortunately, no effective treatment has been yet found for URPL. There are some hypotheses about the role of immunological factors in URPL. Hydroxychloroquine (HCQ) has various immunological effects and may theoretically have a role in the treatment of URPL. Although few studies have been registered to investigate the effect of HCQ on URPL, none of them has been published. What do the results of this study add? In our double-blind placebo-controlled trial, the prevalence of abortion in the HCQ group was four times lower than that in the placebo group, however, this difference was not statistically significant, which can be attributed to the small sample size. What are the implications of these findings for clinical practice and/or further research? We hope that HCQ will be of interest to researchers and future research help clarify the role of HCQ in preventing URPL.

Moini, J., et al. (2019). "A comprehensive review of clinical studies with herbal medicine on polycystic ovary syndrome (PCOS)." DARU, Journal of Pharmaceutical Sciences 27(2): 863-877.
	Background: Polycystic ovary syndrome (PCOS) is a frequent medical condition characterized by both metabolic and reproductive disorders. Different pharmaceutical treatments have been proposed for PCOS. However, side effects of long-term treatments and their probable low efficacy have made complementary and alternative treatments a valuable option. Recent reports have indicated the increased use of complementary treatments. Herbal medicine, as part of complementary medicine, was find introduced in traditional Persian and Chinese medicine. Medicinal herbs have used for a long time in the treatment of gynecological and infertility problems of PCOS patients. In this study, we aimed to review herbal medicines used for PCOS worldwide. Method(s): PubMed, Embase, Cochrane, and Scopus databases were searched for clinical trials and Randomized Controlled Trials based on related keywords. Data were collected from 1990 to 2019. Result(s): According to a multitude of studies, a wide spectrum of herbs can be used to improve various aspects of PCOS. Herbs such as Cinnamomum verum, Trigonella foenum-graecum L., and Vitex agnus-castus can impact on menstrual and ovulatory dysfunctions, obesity, insulin resistance, lipid-metabolism dysfunction, and androgen excess-related conditions. Conclusion(s): Some plants as natural remedies may have beneficial effects on improving different aspects of PCOS; but further studies are needed to investigate their mechanisms and safety.Copyright © 2019, Springer Nature Switzerland AG.

Mojaverrostami, S., et al. (2019). "The role of melatonin in polycystic ovary syndrome: A review." International Journal of Reproductive Biomedicine 17(12): 865-882.
	Background: Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder, affecting approximately 20% of women within reproductive age. It is associated with hyperandrogenism, obesity, menstrual irregularity, and anovulatory infertility. Melatonin is the main pineal gland hormone involved in the regulation of the circadian rhythm. In recent years, it has been observed that a reduction in melatonin levels of follicular fluid exists in PCOS patients. Melatonin receptors in the ovary and intrafollicular fluid adjust sex steroid secretion at different phases of ovarian follicular maturation. Moreover, melatonin is a strong antioxidant and an effective free radical scavenger, which protects ovarian follicles during follicular maturation. Objective(s): In this paper, we conducted a literature review and the summary of the current research on the role of melatonin in PCOS. Material(s) and Method(s): Electronic databases including PubMed/MEDLINE, Web of Science, Scopus, and Reaxys were searched from their inception to October 2018 using the keywords "Melatonin" AND "Polycystic ovary syndrome" OR "PCOS." Results: Based on the data included in our review, it was found that the administration of melatonin can improve the oocyte and embryo quality in PCOS patients. It may also have beneficial effects in correcting the hormonal alterations in PCOS patients. Conclusion(s): Since metabolic dysfunction is the major finding contributing to the initiation of PCOS, melatonin can hinder this process via its improving effects on metabolic functions.Copyright © Mojaverrostami et al.

Mojgan, M., et al. (2021). "The effect of fenugreek on management of dysmenorrhea."
	
Mojgan, M., et al. (2021). "The effect of oral vitamin E and omega-3 alone and in combination on menopausal hot flashes: A systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Mojgan, M. and M. Zahra (2021). "Comparing the effect of honey and clotrimazole in treatment of vaginal candidiasis." PROSPERO International prospective register of systematic reviews.
	
Mojica, P., et al. (2019). "Prenatal Depression and Anxiety: a Literature Review." MedUNAB 22(2): 200-212.
	Introduction. Women with prenatal depression and anxiety may suffer issues in their social performance, emotional withdrawal and excessive worrying about their future ability to be mothers. Objective. To identify and describe the findings that literatura reports on risk factors for developing prenatal depression and anxiety, the consequences for the mother and child, theoretical explanations that cover origin and treatment, and health care strategies. Methodology. We performed a literature review on articles published between 1995 and 2015 on the PubMed, EBSCO Host, Scielo, Redalyc and Google Scholar databases and sources of information. The terms, "depression during pregnancy," "antenatal anxiety," "perinatal mental health," and "prenatal anxiety," among others, were used. Moreover, we selected articles that reported risks and impacts on the mother and child's health, theoretical explanations on its origin and treatments for depression and anxiety. Results. The main identified risk factor is a previous history of anxiety and/or depression at some point in life. A restriction to prenatal development, a low birth weight and premature labor all stand out as some of the negative effects on the baby's health. Going forward, emotional and behavioral issues in the child stand out. Action strategies consist of designing clinical care guides and protocols that allow identifying women who are at risk and women who already present a moderate or severe symptomatology. Conclusions. The above results bring to light the need to implement action strategies that allow identifying populations at risk early. Cómo citar. Mojica-Perilla M, Redondo-Rodríguez S, Osma-Zambrano SE. Depresión y ansiedad prenatal: una revisión de la literatura. MedUNAB. 2019;22(2):200-212. doi: 10.29375/01237047.2820

Mojtahedi, M. F., et al. (2023). "The effect of letrozole as an adjunct in GnRH-antagonist protocol on IVF/ICSI outcome in women with endometriosis: a randomized clinical trial." Middle East Fertility Society Journal 28(1).
	Background: To evaluate the effect of adding letrozole to the antagonist ovarian stimulation protocol (COS) on in‐vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome in endometriosis patients. Methods: This randomized clinical trial was carried out in the department of infertility treatment at Arash Women’s Hospital from May 2019 to May 2021. The eligible women with normal ovarian reserve tests who had endometriosis diagnosis and underwent IVF/ICSI cycles were evaluated. A flexible regimen of GnRH‐antagonist protocol was used for COS. In the experimental (n = 34), the patients received 5 mg letrozole daily for the first 5 days in combination with 150 IU of recombinant follicle‐stimulating hormone (rFSH). In the control group (n = 30), the patients received only the same dose of rFSH. The treatment cycle was compared between groups. Results: Analysis of demographic characteristics, severity of endometriosis, and baseline hormonal tests of patients showed that the two groups were similar and comparable. The means of total used gonadotropins ampoules and serum E2 level on oocyte trigger day in the letrozole group were significantly lower than those of in the control group (P = 0.03 and P = 0.004, respectively). No statistically significant difference in terms of the total number of retrieved and MII oocytes as well as the total numbers of obtained and top‐quality embryos, and cryopreserved embryos was found. Conclusion: The co‐treatment of letrozole with gonadotropins during the antagonist protocol was associated with a reduction in the total dose of gonadotropins, although it had no effect on the oocyte or embryo yield in patients with endometriosis. Trial registration: The study was registered in the Iranian Registry of Clinical Trials on 2018 ‐07‐13 (IRCT20150310021420N4 at www.irct.ir , registered while recruiting).

Mokhtari, F., et al. (2019). "Effects of Melatonin Administration on Chemical Pregnancy Rates of Polycystic Ovary Syndrome Patients Undergoing Intrauterine Insemination: A Randomized Clinical Trial." International Journal of Fertility & Sterility 13(3): 225-229.
	Background: Oxidative stress as a potential cause of poor oocyte quality can influence a female's reproductive system. This study aimed to investigate the effects of melatonin on chemical pregnancy rates of a significant number of polycystic ovary syndrome (PCOS) patients undergoing intrauterine insemination (IUI).; Materials and Methods: In this double-blinded randomized clinical trial (RCT) study, the samples included 198 PCOS patients fulfilling the inclusion criteria and undergoing the IUI treatment. On the third day of menstruation, a 3-mg melatonin tablet or its placebo was given to the patients according to the randomized study protocol; this prescription was continued until the day of human chorionic gonadotropin (hCG) administration. The current study attempted primarily to scrutinize the effect of melatonin administration on the rate of chemical pregnancy and mature follicles during the IUI treatment cycle, and secondarily to determine the endometrial thickness (ET) on the day of IUI.; Results: The mean age of the participants in the study was 28.9 ± 5.5 years. The chemical pregnancy rate in the group receiving melatonin was about 32%, when it was 18% in the control group (P=0.012). Furthermore, it was concluded that the addition of melatonin to the treatment cycle of PCOS individuals could significantly improve the ET after the treatment (P<0.001).; Conclusion: The results of this study demonstrated that the treatment of PCOS patients undergoing IUI with melatonin significantly improves the rate of chemical pregnancy (Registration number: IRCT2017021132489N1).; Competing Interests: The authors declare no conflicts of interest. (Copyright© by Royan Institute. All rights reserved.)

Moldassarina Rymgul, S., et al. (2023). "The importance of vitamin D in the diagnosis and treatment of adenomyosis." Molecular and cellular biochemistry 478(3): 571-579.
	There is still no unified theory of the occurrence of adenomyosis. The theories of retrograde menstruation, metaplasia, activation of Mullerian residues, lymphatic and vascular dissemination, iatrogenic dissemination, immunological changes, genetic predisposition, etc. are discussed. The theory of retrograde menstruation is the most relevant among all these theories. The aim is to study the content of folic acid, vitamins B1, D, E, ferritin in the blood, zinc, copper, calcium in the blood and removed uterine tissues, to assess the hormonal status in women with combined uterine pathology leiomyoma and adenomyosis. 150 women underwent a health examination, residents of the cities of Pavlodar and Nur-Sultan, aged 18 to 49 years with benign dishormonal diseases of reproductive organs (the main group). The control group consisted of 40 women without gynaecological pathology. The study of the somatic status, objective general somatic, clinical and laboratory, gynaecological examination was carried out by routine methods. Ultrasound examination was performed for mammary glands, thyroid gland, pelvic organs in a real-time mode according to standard methods. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Moldovan, N., et al. (2022). "A population-based study of outcomes in adjuvant radiotherapy for stage II endometrial carcinoma." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Objective: Our study aimed to analyze recurrence and survival outcomes in stage II endometrial cancer patients treated with adjuvant radiotherapy at CancerCare Manitoba, a Canadian provincial cancer program.; Methods: This retrospective population-based cohort study identified all International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid type endometrial carcinoma diagnosed between January 1995 and December 2019. All patients underwent surgery followed by vaginal vault brachytherapy alone or external beam pelvic radiotherapy plus vaginal vault brachytherapy. We used Kaplan-Meier curves to describe overall survival and recurrence-free survival, and cumulative incidence to describe recurrence. Cox regression was used to predict overall survival and recurrence-free survival competing risk regression to predict recurrence.; Results: A total of 121 patients were included (78 vaginal brachytherapy alone and 43 external beam pelvic radiotherapy plus vaginal brachytherapy) with a median age of 62 (range 24-85). The median follow-up was 55.2 months (range 7.1-147.9) in the vaginal brachytherapy group and 41.9 months (range 7.4-127.0) in the pelvic radiotherapy group. Lymph node dissection was performed in 79 (65.3%) patients. There were 14 (17.9%) recurrences (8 vaginal vault, 3 pelvic, 3 distant) with vaginal brachytherapy and 7 (16.3%) recurrences (3 vaginal vault, 2 pelvic, 2 distant) with external beam pelvic radiotherapy. The 5 year overall survival was 73.1% with vaginal vault brachytherapy vs 73.7% with external beam pelvic radiotherapy plus vaginal brachytherapy (p=0.31), the 5 year recurrence-free survival was 65.0% vs 68.2% (p=0.61), and the 5 year recurrence risk was 20.3% vs 19.4% (p=0.94). On univariable and multivariable analysis, only age was a statistically significant predictor for overall survival and recurrence-free survival (p<0.05), but not lymphovascular space invasion (HR, 2.97; 95% CI, 0.99 to 8.93 for overall survival, p=0.15). The type of adjuvant radiotherapy did not predict for recurrence (p=0.94).; Conclusions: There was no significant difference in overall survival, recurrence-free survival, and recurrence risk between vaginal vault brachytherapy vs external beam pelvic radiotherapy plus vaginal vault brachytherapy in patients with stage II endometrial cancer.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Molin, J., et al. (2023). "Free leptin index, excessive weight gain, and metformin treatment during pregnancy in polycystic ovary syndrome: What about inflammation?" BJOG : an international journal of obstetrics and gynaecology 130(7): 841-842.
	
Molin, J., et al. (2022). "Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome: A longitudinal, placebo-controlled study." BJOG : an international journal of obstetrics and gynaecology 129(7): 1112-1121.
	Objective: To explore mechanisms that modulate gestational weight gain (GWG) in women with polycystic ovary syndrome (PCOS) and healthy controls.; Design: Sub-sample of randomised controlled trials (PCOS) combined with a prospective cohort (controls).; Setting: Eleven Norwegian, Swedish, and Icelandic hospitals.; Population: Pregnant women with PCOS treated with metformin (PCOS-M, n = 36) or placebo (PCOS-P, n = 37), and healthy pregnant women (HC, n = 15).; Methods: Serum levels of the appetite regulating hormones leptin, ghrelin, allopregnanolone, and soluble leptin receptor (sOB-R) were determined in the first and third trimesters.; Main Outcome Measures: Excessive GWG (eGWG) relative to body mass index according to Institute of Medicine (IOM) guideline. Serum leptin/sOB-R ratio, or free-leptin-index (FLI), as biomarker of leptin sensitivity. Serum ghrelin and allopregnanolone levels.; Results: The overall prevalence of eGWG was 44% (38/86). Women with eGWG had higher first and third trimester FLI (P < 0.001), and lower third trimester allopregnanolone levels (P = 0.003) versus women with non-eGWG. The prevalence of eGWG was lower in PCOS-M versus PCOS-P (28% versus 62%, odds ratio = 0.4, 95% CI 0.2-0.8, P = 0.005). FLI decreased during pregnancy in PCOS-M (P = 0.01), but remained unaltered in PCOS-P and HC. Ghrelin and allopregnanolone levels were comparable in PCOS-M, PCOS-P and HC throughout pregnancy.; Conclusion: Excessive GWG is associated with enhanced leptin resistance, and attenuated physiological increase in serum allopregnanolone levels during pregnancy. Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS.; Tweetable Abstract: Metformin counteracts excessive weight gain and leptin resistance in pregnant women with polycystic ovary syndrome. (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Molina-Torres, G., et al. (2023). "The effects of an 8-week hypopressive exercise training program on urinary incontinence and pelvic floor muscle activation: A randomized controlled trial." Neurourology and Urodynamics 42(2): 500-509.
	Background: Pelvic floor dysfunction and urinary incontinence are two of the most frequent gynecological problems, and pelvic floor muscle training is recommended as a first-line treatment, with new approaches such as hypopressive exercises. This study aimed to analyze the efficacy of an 8-week supervised training program of hypopressive exercises on pelvic floor muscle strength and urinary incontinence symptomatology.; Design: Blinded randomized controlled trial.; Settings: Women with pelvic floor dysfunction and urinary incontinence symptoms, aged 18-60 years.; Participants: A total of 117 participants were randomly allocated to the hypopressive exercises group (n = 62) or a control group that received no intervention (n = 55) and completed the study.; Main Outcome Measures: Clinical and sociodemographic data were collected, as well as pelvic floor muscle strength (using the Modified Oxford Scale); the genital prolapse symptoms, colorectal symptoms, and urinary symptoms (with the Pelvic Floor Distress Inventory [PFDI-20]); the impact of pelvic floor disorders (PFD) on women's lives (with the Pelvic Floor Impact Questionnaire [PFIQ-7]); and the severity of urinary incontinence symptoms (using the International Consultation on Incontinence Questionnaire [ICIQ]).; Results: The results showed an improvement in the hypopressive group in the pelvic floor muscle strength F (1117) = 89.514, p < 0.001, a significantly lower score for the PFIQ7 total score, t (112) = 28.895, p < 0.001 and FPDI20 t (112) = 7.037, p < 0.001 as well as an improvement in ICIQ-SF values after 8 weeks of intervention in comparison with the control group.; Conclusions: After performing an 8-week of hipopressive exercises intervention, a decrease in pelvic floor disorders associated symptoms can be observed. In addition, pelvic floor muscle contractility is improved and a decrease in severity and symptoms associated with urinary incontinence has been reported. (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Moliner, B., et al. (2021). "The Effect of Twisted Uterus Caused by Endometriosis or Myomatosis on Reproductive Treatment Outcomes." Journal of family & reproductive health 15(2): 106-111.
	Objective: Twisted uterus is detected when the body of the uterus is rotated from the cervical canal. This anomaly may be due to different causes, such as uterine fibroids, endometriosis or the presence of both. The study has aimed to compare the effect of the twisted uterus cause in terms of reproductive treatment outcomes. Materials and methods: It consisted of a retrospective study of twisted uterus cases with repeated implantation failure (more than three embryo transfers or four blastocysts transferred unsuccessfully) in our ultrasound department. The twisted uterus was defined when the vaginal probe needed to be rotated to assess the endometrial line thoroughly or when the coronal view was seen by 2D scan. From 2017 to 2020, 879 gynecological ultrasounds were performed. For statistical analysis, we carried out a logistical regression analysis adjusted by confounding factors. Results: From 145 patients included only 92 patients underwent reproductive treatments. With the known cause of uterine torsion. 56 patients with endometriosis, 18 with uterine myoma and the remaining 18 suffered from both. After assisted reproductive treatment, the endometriosis group showed the highest clinical pregnancy rate (53.57%) compared to myoma (22.22%) and endometriosis and myoma (38.89%) groups. Conclusion: Uterine myoma capable of causing uterine torsion may affect embryo implantation more than endometriosis. Prospective randomized studies with a larger number of patients would be needed to confirm these findings.

Mollaahmadi, L., et al. (2019). "Evaluation and comparison of the effects of various cognitive-behavioral therapy methods on climacteric symptoms: A systematic review study." Journal of the Turkish German Gynecological Association 20(3): 178-195.
	Objective: Climacteric syndrome, which is related to many symptoms, often causes discomfort in women. Non-pharmacologic treatment is one of the treatment options for affected individuals, and this syndrome can be cured with psychological treatments such as cognitive behavioral therapy (CBT). The present study aimed to compare the efficacy of various CBT methods on the improvement of climacteric symptoms.; Material and Methods: PubMed, Scopus, Cochrane, Medline, PsycINFO, and Google Scholar were searched for relevant articles published between January 1990 and August 2018. Data extraction and quality assessment were conducted by two authors.; Results: A total of 15 articles including 910 women were entered. We divided the CBT methods into two categories, face-to-face (individual and group CBT) and indirect (self-help CBT) methods. Among the three CBT approaches, three articles covered individual CBT, nine articles carried out group CBT, and in five articles, the self-help approach was used. The climacteric symptoms that improved with CBT were categorized into three groups as vasomotor symptoms, psychological symptoms, and organic disorders. Generally, the face-to-face method played a key positive effect on symptom improvement, and the group CBT approach was more effective on psychological symptoms.; Conclusion: Although the indirect method is more cost-effective, it has less impact than the face-to-face method; it is better to use face-to-face approaches to achieve better results, if possible. Further studies are required in this regard, particularly in the individual and self-help CBT approaches, to measure the impact of these approaches on more varied symptoms of menopause.

Mollah, T. and J. Brennan (2023). "Australian trends in the treatment of pelvic organ prolapse in the non-mesh era." ANZ journal of surgery 93(3): 469-475.
	Background: To assess the contemporary trends in the types and incidence of pelvic organ prolapse (POP) surgery in Australia after the removal of transvaginal mesh from the Australian market.; Methods: This was a retrospective Australian cohort study utilizing three large Governmental databases covering all private and public POP procedures in Australia. All females ≥25 years old undergoing POP procedures between 2005 and 2021 were included.; Results: From 2005-2006 to 2020-2021 there have been a total of 408 881 POP procedures in Australia. The total number of procedures peaked in 2005-2006 at 537.8 procedures per 100 000 age-standardized female population, decreasing by an average of 3.5% per year to 329.0 procedures per 100 000 in 2018-2019, an overall 38.8% decrease (P < 0.001). A sudden growth in private operative procedures was noted between 2019-2020 and 2020-2021, from 218.2 to 268.6 procedures per 100 000 population, a 23.1% increase (P < 0.001). Laparoscopic and abdominal POP repair has seen a 115.8% increase from 13.7 procedures to 29.6 per 100 000 between 2005-2006 and 2020-2021. Over the last 15 years, the most common age group to undergo a procedure has changed from the 55 to 64 years demographic to a later decade of 65 to 74 years.; Conclusion: Over the last 15 years, the total number of POP procedures performed has significantly decreased. There has however been a recent rise in interventions seen in the private sector and the utilization of laparoscopic or abdominal POP repair has increased, which has implications for procedural credentialing to ensure patient safety. (© 2023 Royal Australasian College of Surgeons.)

Mollazadeh, S., et al. (2019). "The effects of Vitex agnus-castus on menstrual bleeding: A systematic review and meta-analysis." Journal of complementary & integrative medicine 17(1).
	Introduction Vitex agnus-castus, also called Vitex, is a plant with many medicinal properties. This systematic study examined the evidence of the effectiveness and safety of Vitex on menstrual bleeding (primary outcome) and its side effects (secondary outcomes). Materials and methods This systematic review study examined all papers that were a randomized controlled trial, quasi-experimental, and cross-over conducted on the effect of Vitex on menstrual bleeding, following the PICO (population, intervention, control, and outcomes) criteria without any time limits in December 2017. The participants were women of reproductive age with no gynecologic disorders. The intervention included the use of Vitex in form of tablets, capsule, or oral drops with different doses. The control group included the placebo or mefenamic acid group. The search strategy in this study was in accordance with MeSH terms. The keywords used separately or in combination with other words were Menstrual bleeding OR Menstruation OR Menorrhagia AND Vitexcastus OR Vitex OR Chasteberry AND randomized controlled trial OR randomized trial OR randomized clinical trial OR randomized controlled. All papers, including Persian or English, were searched for in the databases; Medline (through PubMed), Scopus, Embase (through Ovid), Cochrane Library, Web of Sciences, Google Scholar, SID, Magiran, Irandoc, and Iranmedex, without any time limits. Two authors independently reviewed the quality of the papers and assessed the risk of bias based on Cochrane handbook, and the disputes were resolved through discussion and consensus with a third person. The meta-analysis was done on continuous data (mean of menstrual bleeding). In meta-analysis, subgroup analysis was performed based on the type of comparison group. Results Out of the 8,905 searched papers in the databases, 8,905 titles, 720 abstracts, 85 full texts, and 20 references of the papers were reviewed, of which 5 papers entered this study. Based on the subgroup analysis, the consumption of Vitex did not have a significant effect on the amount of menstrual bleeding compared to the placebo group in the first (mean difference [MD]: 3.08; 95% CI: -3.11-9.26; p=0.33; I2=0%) and second menstrual cycles (MD: 0.00; 95% CI: -5.75-5.75; p=1.00; I2=0%). Also, the Higham mean score was statistically more in the Vitex group compared to the mefenamic acid group in the first menstrual cycle (MD: 7.17; 95% CI: 0.33-14.01; p=0.04; I2=0%) but there was no statistical significant difference between Vitex and mefenamic acid groups in the second menstrual cycle (MD: 12.18; 95% CI: -5.57-29.94; p=0.18; I2=75%). Only nausea and abdominal pain were reported as side effects of Vitex in the included studies. Conclusions The results of this study showed that the consumption of Vitex in the intervention group did not have a significant effect on menstrual bleeding in comparison with the placebo group. However, due to the relatively low quality of the papers, it is essential to perform clinical trials with an appropriate design to determine the effect of Vitex on menstrual bleeding.

Mollazadeh-Narestan, Z., et al. (2023). "Comparing the Effect of Probiotic and Fluconazole on Treatment and Recurrence of Vulvovaginal Candidiasis: a Triple-Blinded Randomized Controlled Trial." Probiotics and Antimicrobial Proteins 15(5): 1436-1446.
	Vaginitis is a common problem in women. Candida albicans is responsible for more than 85% of vaginal fungal infections. The aim of this study was to compare the effects of probiotic and fluconazole on the treatment and recurrence of vulvovaginal candidiasis (VVC). This triple-blinded randomized controlled trial was conducted on 80 married women, aged 18-49 years, with VVC, as confirmed by clinical and laboratory diagnosis. The participants were allocated into two groups using blocked randomization method. The fluconazole-treated group received a single dose of fluconazole (150 mg) supplemented with 30 placebo capsules of probiotic, and the probiotic-treated group got 30 probiotic capsules containing 1 x 109 CFU/g LA-5 with 1 fluconazole placebo capsule. The samples were taken from patients to evaluate the vaginal pH and microbiological tests before, 30-35 days, and 60-65 days after starting the treatment. The signs and symptoms were assessed before the intervention and the first and second follow-ups. Chi-square, Fisher's exact, independent t, and ANCOVA tests were then used for data analysis. There was no statistically significant difference between the two groups (p = 0.127) in the frequency of negative culture 30-35 days after starting the treatment, but the frequency of negative culture 60-65 days after starting treatment in the fluconazole group was significantly higher than that of the probiotic group (p = 0.016). The abnormal discharge and vulvovaginal erythema in the first and second follow-ups and also pruritus in the second follow-up in the fluconazole group were significantly lower than those in the probiotic group (p < 0.05). There was, however, no statistically significant difference in burning, frequent urination, dysuria, and dyspareunia between the groups (p > 0.05). Lactobacillus acidophilus supplementation had an effect similar to that of fluconazole in treating most symptoms of VVC, but it was less effective than the latter in preventing recurrence. Trial Registration: Iranian Registry of Clinical Trials (IRCT): IRCT20110826007418N5. Date of registration: 3 March 2021; URL: https://en.irct.ir/trial/50819; Date of first registration: 10 March 2021.Copyright © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Mollazadeh-Narestan, Z., et al. (2023). "Comparison of the Efficacy of Honey and Clotrimazole Cream in the Vulvovaginal Candidiasis Treatment: A Systematic Review and Meta-analysis." Current Drug Therapy 18(2): 164-174.
	Background: Vulvovaginal candidiasis (VVC) is a common fungal infection of the vaginal area affecting 75% of women at least once in their lifetime. However, there is no clear evidence help-ing to choose the most effective treatment method to improve the symptoms of VVC. Objective(s): The objective of this study was to compare the effect of using honey with clotrimazole on the treatment of symptoms of VVC. Method(s): All databases in English (Embase, MEDLINE, ProQuest, Google Scholar, Scopus, Cochrane Library, and Web of Science) and Persian (Irandoc, SID, and Magiran) were searched with-out time limitation. Evaluation of studies in terms of bias was performed using the Cochrane hand-book. Four clinical trials were included in the present systematic review; however, only three of them were included in the meta-analysis. Result(s): The results of the meta-analysis demonstrated that the rate of positive culture after treatment (RR: 2.35; 95%CI: 1.45 to 3.82) was significantly higher in the honey group than in the clotrimazole one. The frequency of itching after treatment (RR: 0.25, 95%CI: 0.12 to 0.49) was significantly lower in the honey-receiving group than in the clotrimazole one. However, there was no statistically significant difference in the incidence of other symptoms of VVC, including vaginal discharge (RR: 0.26, 95%CI: 0.02 to 2.75), vaginal burning (RR: 0.35, 95%CI: 0.03 to 3.80) and dyspareunia (RR: 0.64, 95%CI: 0.27 to 1.50) between groups. Conclusion(s): Due to the low quality of the studies, more clinical trial studies with stronger designs in this field are needed to clearly identify the therapeutic effects of honey on improving the symptoms of VVC. Prospero ID: CRD42021250658.Copyright © 2023 Bentham Science Publishers.

Molnár, T., et al. (2022). "Utilizing Synergism between the Transverse Abdominal and Pelvic Floor Muscles at Different Postures in Nulliparous Women: A Randomized Case-Control Study." Urologia internationalis 106(3): 274-281.
	INTRODUCTION: The aim of the study was to determine the effects of the pelvic floor muscle (PFM) training (PFM-T) in combination with transverse abdominal (TRA) muscle activation (cPFM-T) in female urinary incontinence. METHODS: We enrolled nulliparous women in supine (SUG) (n = 22), sitting (SIG) (n = 19), and control (COG) (n = 14) groups. We conducted an 8-week cPFM-T programme. We examined the effect of training on the parameters with the Kruskal-Wallis test, the pairwise comparisons with the Mann-Whitney U test, and the Wilcoxon rank test with the Bonferroni correction. RESULTS: Before training, 15 participants reported occasional urinary leakage. After cPFM-T, 7 participants reported that urinary leakage had disappeared. Maximal isometric contraction of the PFMs until fatigue improved significantly in the SUG (p < 0.001) and SIG (p = 0.015) groups but not significantly in the COG group (p = 0.499). Holding time increased in the SUG (p = 0.972) and the SIG (p = 0.717) groups and decreased in the COG group (p = 0.132). The dynamic endurance of the PFM improved significantly in the SUG group (p < 0.001) but not in the SIG (p = 0.798) and the COG (p = 0.153) groups. The number of maximal fast contractions within 1 min increased in both the SUG (p < 0.001) and SIG (p = 0.813) groups and decreased in the COG group (p = 0.257). Relaxation improved significantly in the SIG group (p = 0.011). TRA mucle thickness increased in both training groups. CONCLUSION: Slow-twitch fibres of the PFM can be trained effectively with PFM-T in both the body positions.

Moloud, F. and H. Zeinab (2022). "The effect of natural products on heavy menstrual bleeding: A systematic review and meta-analysis of randomized clinical trials." PROSPERO International prospective register of systematic reviews.
	
Momoeda, M., et al. (2022). "Quality of Life of Japanese Dysmenorrhea/Heavy Menstrual Bleeding Patients Treated with Levonorgestrel Intrauterine Delivery System in a Real-World Setting." Advances in Therapy 39(8): 3616-3634.
	Introduction: The present study collected 1-year follow-up patient-reported outcome data from Japanese women with dysmenorrhea and/or heavy menstrual bleeding (HMB) who underwent insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg. We aimed to evaluate the quality of life (QOL) of Japanese women over the course of the investigational period.; Methods: This was a multicenter, non-interventional, prospective, single-cohort, post-marketing surveillance study (J-MIRAI). The primary outcome was the median change in the Menstrual Distress Questionnaire (MDQ) and Menorrhagia Multi-Attribute Scale (MMAS) scores from baseline to 3 and 12 months after LNG-IUS insertion, with decreasing and increasing scores, respectively, indicating improvement. The secondary outcomes were the statistical relationships between the MDQ and menstrual pain (measured by a visual analog scale, VAS), and between the MMAS and pictorial blood loss assessment chart (PBAC) scores by regression analysis.; Results: In total, 593 patients were evaluated; 376, 467, and 250 patients were diagnosed with dysmenorrhea, HMB, or both, respectively. The median MDQ score decreased significantly at 3 and 12 months after LNG-IUS insertion in both the premenstrual and menstrual periods (both p < 0.001 vs baseline), and the median MMAS score showed a similar improvement during the menstrual period. Changes in median MDQ and MMAS scores were observed regardless of patient background. Correlations between MDQ and menstrual pain (VAS) and between MMAS and PBAC scores were found (estimated regression coefficients 0.29 and - 0.15, respectively).; Conclusion: The LNG-IUS contributed to improvements in the QOL of patients with dysmenorrhea, HMB, and both, regardless of patient background characteristics.; Trial Registration: Registered at ClinicalTrials.gov (NCT02475356) on 18 June 2015. (© 2022. The Author(s).)

Monk, B., et al. (2022). "Patient-Reported Outcomes from the Phase 3 Randomized, Double-Blind, KEYNOTE-826 Trial of Pembrolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer (023)." Gynecologic Oncology 166(Supplement 1): S18.
	Objectives: In the ITT population of the KEYNOTE-826 study of patients with persistent, recurrent, or metastatic cervical cancer (NCT03635567), adding pembrolizumab (pembro) to chemotherapy (chemo) +/- bevacizumab (bev) provided a substantial, clinically meaningful, and statistically significant improvement in OS (median 24.4 vs 16.5 mo; HR 0.67, P<0.001) and PFS (median 10.4 vs 8.2 mo; HR 0.65, P<0.001) versus placebo plus chemo +/- bev (N Engl J Med 2021;doi: 10.1056/NEJMoa2112435). We report patient-reported outcomes (PROs) from KEYNOTE-826. Method(s): Patients were randomized 1:1 to pembro 200 mg or placebo Q3W for <=35 cycles plus chemo (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) +/- bev 15 mg/kg Q3W. PRO instruments were the EORTC Quality-of-Life-Core 30 (QLQ-C30), EORTC Cervical Cancer module (QLQ-CX24), and the EuroQol (EQ)-5D-5L VAS, each collected before treatment at cycles 1-14 and every other cycle thereafter. Change from baseline in QLQ-C30 global health status (GHS)/quality of life (QoL) was a secondary endpoint. Other PRO analyses were protocol-specified exploratory endpoints. PRO analyses included patients with >=1 dose of study medication and >=1 post-baseline PRO assessment. Per protocol, PROs were classified as improved with a >=10-point change from baseline to week 30 (last time with completion/compliance >=60%/>=80%), and time to true deterioration (TTD) was the time from baseline to first onset of a >=10-point worsening with confirmation under the right censoring rule or death, whichever occurred first. Result(s): Of 617 patients randomized, 566 were in the PRO analyses (281 with pembro-chemo and 285 with placebo-chemo). PRO completion/compliance at week 30 was 68.6%/94.3% with pembro-chemo and 56.6%/90.3% with placebo-chemo. Baseline QLQ-C30 GHS/QoL and EQ-5D VAS scores were similar between treatment groups. Mean changes from baseline in QLQ-C30 GHS/QoL were similar between groups (difference in mean changes, 1.01). The HR for TTD of GHS/QoL was 0.84 (95% CI 0.65-1.09), with 12-mo estimates of patients free from deterioration of 57.3% for pembro-chemo and 51.1% for placebo-chemo. More patients with pembro-chemo had an improved GHS/QoL compared with placebo-chemo (42.1% vs 28.6%). There were no meaningful differences in changes in physical functioning (difference in mean changes, 2.1). A prolonged TTD in EQ-5D VAS was observed with pembro-chemo compared with placebo-chemo (12-month estimate of patients free from deterioration, 58.2% vs 44.8%; HR 0.75; 95% CI 0.58-0.97). More patients with pembro-chemo had an improved EQ-5D-5L VAS (42.8% vs 36.4%). Conclusion(s): Significant improvements in OS and PFS due to the addition of pembro to the standard of care for patients with recurrent, persistent, or metastatic cervical cancer were not accompanied by any substantial deterioration in QoL. Pembro-chemo with or without bev resulted in more patients with improved EORTC QLQ-C30 GHS/QoL and prolonged TTD for EQ-5D-5L compared with placebo-chemo.Copyright © 2022 Elsevier Inc.

Monk, B., et al. (2022). "DURVALUMAB, IN COMBINATION WITH AND FOLLOWING CHEMORADIOTHERAPY, IN LOCALLY ADVANCED CERVICAL CANCER: RESULTS FROM THE PHASE 3 INTERNATIONAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CALLA TRIAL." International Journal of Gynecological Cancer 32(Supplement 3): A2-A3.
	Objectives In locally-advanced cervical cancer (LACC), platinum- based chemoradiotherapy (CRT) has been the standardof- care treatment for >20 years. CALLA is the first global Phase 3 study evaluating immune checkpoint inhibition (durvalumab) versus placebo in combination with and following CRT in LACC (NCT03830866). Methods Newly-diagnosed, untreated patients with LACC (FIGO 2009 stages IB2-IIB node positive, IIIA-IVA with any node status) were randomized 1:1 to durvalumab (1500 mg IV) or placebo Q4W, for a total of up to 24 months, in combination with and following CRT. CRT comprised concurrent weekly IV cisplatin with EBRT and brachytherapy. RT quality was monitored, with variations evaluated for clinical significance. The primary endpoint is PFS; secondary endpoints include OS, objective response rate, local/distant disease progression incidence, and safety. Results 770 patients were randomized (N=385 per arm) at 120 sites in 15 countries. Median age was 49 years; median follow-up was 18.5 months. Durvalumab+CRT did not show a statistically significant improvement in PFS vs placebo+CRT (HR 0.84 [95% CI, 0.65-1.08]; P=0.174); there was no detriment to OS, although data were immature and not formally tested. Adverse events of grade 3-4 occurred in 51.7% and 51.0% of patients in the durvalumab+CRT and placebo+CRT arms, respectively; 12.5% and 9.6% of patients discontinued treatment due to AEs possibly related to study drug. Conclusions Durvalumab in combination with and following CRT did not significantly improve PFS in patients with LACC. Safety of durvalumab+CRT was generally comparable to CRT alone, with no new or unexpected toxicity. Funding(s): AstraZeneca.

Monk, B. J., et al. (2021). "ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(12): 1589-1594.
	BACKGROUND: The optimal treatment strategy for women with newly diagnosed ovarian cancer has yet to be determined. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated substantial improvement in progression-free survival as monotherapy maintenance treatment in the frontline setting versus active surveillance. Furthermore, preclinical and early clinical studies have shown that PARP inhibitors and immune checkpoint inhibitors have synergistic antitumor activity and may provide an additional therapeutic option for patients in this population. PRIMARY OBJECTIVES: In women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer, we wish to assess the efficacy of frontline maintenance treatment with the PARP inhibitor rucaparib versus placebo following response to platinum-based chemotherapy (ATHENA-MONO), and to assess the combination of rucaparib plus nivolumab (a programmed death receptor 1 (PD-1)-blocking monoclonal antibody) versus rucaparib alone (ATHENA-COMBO). STUDY HYPOTHESIS: (1) Maintenance therapy with rucaparib monotherapy may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting. (2) The combination of nivolumab plus rucaparib may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting compared with rucaparib alone. TRIAL DESIGN: ATHENA is an international, randomized, double-blind, phase III trial consisting of two independent comparisons (ATHENA-MONO and ATHENA-COMBO) in patients with newly diagnosed platinum-sensitive ovarian cancer. Patients are randomized 4:4:1:1 to the following: oral rucaparib+ intravenous nivolumab (arm A); oral rucaparib + intravenous placebo (arm B); oral placebo+ intravenous nivolumab (arm C); and oral placebo + intravenous placebo (arm D). The starting dose of rucaparib is 600 mg orally twice a day and nivolumab 480 mg intravenously every 4 weeks. ATHENA-MONO compares arm B with arm D to evaluate rucaparib monotherapy versus placebo, and ATHENA-COMBO evaluates arm A versus arm B to investigate the effects of rucaparib and nivolumab in combination versus rucaparib monotherapy. ATHENA-MONO and ATHENA-COMBO share a common treatment arm (arm B) but each comparison is independently powered. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients ≥18 years of age with newly diagnosed advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer who have achieved a response after completion of cytoreductive surgery and initial platinum-based chemotherapy are enrolled. No other prior treatment for ovarian cancer, other than the frontline platinum regimen, is permitted. PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival by Response Evaluation Criteria in Solid Tumors v1.1. SAMPLE SIZE: Approximately 1000 patients have been enrolled and randomized. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The trial completed accrual in 2020. While dependent on event rates, primary results of ATHENA-MONO are anticipated in early 2022 and results of ATHENA-COMBO are anticipated to mature at a later date. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov (NCT03522246).

Monk, B. J., et al. (2021). "Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial." The Lancet. Oncology 22(9): 1275-1289.
	BACKGROUND: Although most patients with epithelial ovarian cancer respond to frontline platinum-based chemotherapy, around 70% will relapse within 3 years. The phase 3 JAVELIN Ovarian 100 trial compared avelumab (anti-PD-L1 monoclonal antibody) in combination with chemotherapy followed by avelumab maintenance, or chemotherapy followed by avelumab maintenance, versus chemotherapy alone in patients with treatment-naive epithelial ovarian cancer. METHODS: JAVELIN Ovarian 100 was a global, open-label, three-arm, parallel, randomised, phase 3 trial run at 159 hospitals and cancer treatment centres in 25 countries. Eligible women were aged 18 years and older with stage III-IV epithelial ovarian, fallopian tube, or peritoneal cancer (following debulking surgery, or candidates for neoadjuvant chemotherapy), and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to receive chemotherapy (six cycles; carboplatin dosed at an area under the serum-concentration-time curve of 5 or 6 intravenously every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks or 80 mg/m2 once a week [investigators' choice]) followed by avelumab maintenance (10 mg/kg intravenously every 2 weeks; avelumab maintenance group); chemotherapy plus avelumab (10 mg/kg intravenously every 3 weeks) followed by avelumab maintenance (avelumab combination group); or chemotherapy followed by observation (control group). Randomisation was in permuted blocks of size six and stratified by paclitaxel regimen and resection status. Patients and investigators were masked to assignment to the two chemotherapy groups without avelumab at the time of randomisation until completion of the chemotherapy phase. The primary endpoint was progression-free survival assessed by blinded independent central review in all randomly assigned patients (analysed by intention to treat). Safety was analysed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02718417. The trial was fully enrolled and terminated at interim analysis due to futility, and efficacy is no longer being assessed. FINDINGS: Between May 19, 2016 and Jan 23, 2018, 998 patients were randomly assigned (avelumab maintenance n=332, avelumab combination n=331, and control n=335). At the planned interim analysis (data cutoff Sept 7, 2018), prespecified futility boundaries were crossed for the progression-free survival analysis, and the trial was stopped as recommended by the independent data monitoring committee and endorsed by the protocol steering committee. Median follow-up for progression-free survival for all patients was 10·8 months (IQR 7·1-14·9); 11·1 months (7·0-15·3) for the avelumab maintenance group, 11·0 months (7·4-14·5) for the avelumab combination group, and 10·2 months (6·7-14·0) for the control group. Median progression-free survival was 16·8 months (95% CI 13·5-not estimable [NE]) with avelumab maintenance, 18·1 months (14·8-NE) with avelumab combination treatment, and NE (18·2 months-NE) with control treatment. The stratified hazard ratio for progression-free survival was 1·43 (95% CI 1·05-1·95; one-sided p=0·99) with the avelumab maintenance regimen and 1·14 (0·83-1·56; one-sided p=0·79) with the avelumab combination regimen, versus control treatment. The most common grade 3-4 adverse events were anaemia (69 [21%] patients in the avelumab maintenance group, 63 [19%] in the avelumab combination group, and 53 [16%] in the control group), neutropenia (91 [28%], 99 [30%], and 88 [26%]), and neutrophil count decrease (49 [15%], 45 [14%], and 59 [18%]). Serious adverse events of any grade occurred in 92 (28%) patients in the avelumab maintenance group, 118 (36%) in the avelumab combination group, and 64 (19%) in the control group. Treatment-related deaths occurred in one (<1%) patient in the avelumab maintenance group (due to atrial fibrillation) and one (<1%) patient in the avelumab combination group (due to disease progression). TERPRETATION: Although no new safety signals were observed, results do not support the use of avelumab in the frontline treatment setting. Alternative treatment regimens are needed to improve outcomes in patients with advanced epithelial ovarian cancer. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.

Monk, B. J., et al. (2022). "ATHENA-MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer." Journal of Clinical Oncology 40(17 Supplement).
	Background: While PARP inhibitors have shown efficacy as first-line (1L) maintenance treatment for patients (pts) with ovarian cancer (OC), questions remain about the pt population that may benefit from their use. ATHENA (NCT03522246) was designed to test if rucaparib may be effective as 1L maintenance treatment in a broad pt population, including those without BRCA mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. Here we report results from the ATHENA-MONO comparison of rucaparib vs placebo. Method(s): Pts with stage III-IV highgrade OC who had completed cytoreductive surgery (R0 permitted) and 4-8 cycles of 1L platinum-doublet (bevacizumab allowed with chemotherapy) with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Pts were stratified by HRD status (as determined by FoundationOne CDx), residual disease status after chemotherapy, and timing of surgery. The primary endpoint of investigator-assessed PFS per RECIST was assessed in a step-down procedure first in the HRD population (BRCA mutant or BRCA wild-type/loss of heterozygosity [LOH] high carcinoma) and then in the intent-to-treat (ITT) population. Blinded independent central review (BICR)-assessed PFS was a stand-alone, secondary endpoint. PFS in BRCA mutant and HRD-negative pts (BRCA wild-type/LOH low) were exploratory endpoints. Result(s): As of Mar 23, 2022 (visit cutoff), 427 and 111 pts were randomized to rucaparib monotherapy or placebo (median time on treatment, 14.7 and 9.9 mo). PFS data are shown in the Table. Most common grade ge;3 TEAEs were anemia (rucaparib, 28.7% vs placebo, 0%), neutropenia (14.6% vs 0.9%), and ALT/AST increased (10.6% vs 0.9%). Rucaparib dose reduction, interruption, and discontinuation due to TEAEs occurred in 49.4%, 60.7%, and 11.8% of pts. Conclusion(s): Rucaparib monotherapy is effective as 1L maintenance with significant benefit vs placebo observed in the ITT and HRD populations, as well as the non-nested subgroup of pts without known HRD. (Table Presented).

Monk Bradley, J., et al. (2023). "First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(36): 5505-5511.
	Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The phase III, double-blind KEYNOTE-826 trial of pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with or without bevacizumab, showed statistically significant survival benefits with the addition of pembrolizumab for patients with persistent, recurrent, or metastatic cervical cancer (primary data cutoff: May 3, 2021). This article reports the protocol-specified final overall survival (OS) results tested in the PD-L1 combined positive score (CPS) ≥1, all-comer, and CPS ≥10 populations. At the final data cutoff (October 3, 2022), the median study follow-up duration was 39.1 months (range, 32.1-46.5 months). In the PD-L1 CPS ≥1 (N = 548), all-comer (N = 617), and CPS ≥10 (N = 317) populations, median OS with pembrolizumab-chemotherapy versus placebo-chemotherapy was 28.6 months versus 16.5 months (hazard ratio [HR] for death, 0.60 [95% CI, 0.49 to 0.74]), 26.4 months versus 16.8 months (HR, 0.63 [95% CI, 0.52 to 0.77]), and 29.6 months versus 17.4 months (HR, 0.58 [95% CI, 0.44 to 0.78]), respectively. The incidence of grade ≥3 adverse events was 82.4% with pembrolizumab-chemotherapy and 75.4% with placebo-chemotherapy. These results show that pembrolizumab plus chemotherapy, with or without bevacizumab, continued to provide clinically meaningful improvements in OS for patients with persistent, recurrent, or metastatic cervical cancer.

Monk Bradley, J., et al. (2023). "Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial." The Lancet. Oncology 24(4): 392-402.
	Background: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826.; Methods: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries. Eligible patients were aged 18 years or older with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy (previous radiosensitising chemotherapy was allowed) and not amenable to curative treatment and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) centrally by means of an interactive voice response system in a double-blind manner to receive either pembrolizumab 200 mg or placebo every 3 weeks intravenously for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m 2 plus cisplatin 50 mg/m 2 or carboplatin area under the curve 5 mg/mL per min, intravenously) with or without bevacizumab 15 mg/kg every 3 weeks intravenously. Randomisation (block size of 4) was stratified by metastatic disease at diagnosis, planned bevacizumab use, and PD-L1 combined positive score. Patients, investigators, and other study personnel involved in study treatment administration or clinical evaluation of patients were unaware of treatment group assignments. PRO instruments were the EORTC Quality-of-Life-Core 30 (QLQ-C30), the EORTC cervical cancer module (QLQ-CX24), and the EuroQol-5 dimension-5 level (EQ-5D-5L) visual analogue scale, each collected before treatment at cycles 1-14 and every other cycle thereafter. Primary endpoints were overall survival and progression-free survival per RECIST version 1.1 by investigator review. Change from baseline in QLQ-C30 global health status (GHS)-quality of life (QoL) was a prespecified secondary endpoint and was assessed in the PRO full analysis population (all patients who received at least one dose of study treatment and completed at least one post-baseline PRO assessment). Other PRO analyses were protocol-specified exploratory endpoints. The study is registered with ClinicalTrials.gov, NCT03635567, and is ongoing.; Findings: Between Nov 20, 2018, and Jan 31, 2020, of 883 patients screened, 617 were randomly assigned (pembrolizumab group, n=308; placebo group, n=309). 587 (95%) of 617 patients received at least one dose of study treatment and completed at least one post-baseline PRO assessment and were therefore included in the PRO analyses (pembrolizumab group, n=290; placebo group, n=297). Median follow-up was 22·0 months (IQR 19·1-24·4). At week 30, QLQ-C30 completion was 199 (69%) of 290 patients in the pembrolizumab group and 168 (57%) of 297 patients in the placebo group; compliance was 199 (94%) of 211 and 168 (90%) of 186, respectively. The least squares mean change in QLQ-C30 GHS-QoL score from baseline to week 30 was -0·3 points (95% CI -3·1 to 2·6) in the pembrolizumab group and -1·3 points (-4·2 to 1·7) in the placebo group, with a between-group difference in least squares mean change of 1·0 point (95% CI -2·7 to 4·7). Median time to true deterioration in GHS-QoL was not reached (NR; 95% CI 13·4 months-NR) in the pembrolizumab group and 12·9 months (6·6-NR) in the placebo group (hazard ratio 0·84 [95% CI 0·65-1·09]). 122 (42%) of 290 patients in the pembrolizumab group versus 85 (29%) of 297 in the placebo group had improved GHS-QoL at any time during the study (p=0·0003).; Interpretation: Addition of pembrolizumab to chemotherapy with or without bevacizumab did not negatively affect health-related quality of life. Along with the efficacy and safety results already reported from KEYNOTE-826, these data support the benefit of pembrolizumab and the value of immunotherapy in patients with recurre t, persistent, or metastatic cervical cancer.; Funding: Merck Sharp & Dohme.; Competing Interests: Declaration of interests All authors' institutions received research funding from Merck Sharp & Dohme, a subsidiary of Merck (Rahway, NJ, USA), for the conduct of this study. BJM was a consultant to or received honoraria from AbbVie, Agenus, Akeso Biopharma, Aravive, AstraZeneca, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Serono, Genentech, Genmab–Seattle Genetics, GlaxoSmithKline, GOG Foundation, Gradalis, ImmunoGen, Incyte Corporation, Iovance Biotherapeutics, Janssen Biotech, Karyopharm Therapeutics, Merck, Mersana Therapeutics, Myriad Genetic Laboratories, Novocure, Pfizer, Pfizer International, Puma Biotechnology, Regeneron Pharmaceuticals, Sorrento Therapeutics, Takeda Development Center Americas, US Oncology, and VBL Therapeutics. KST received research grant to institution, and consultant–speaker's bureau fees from Merck. CD was on an endpoint review committee for Merck. KH was a scientific advisory board member and received honoraria, contracted research and study funding to their institution from Merck Sharp & Dohme. RS-F received speaker honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Sanofi, Roche, Medison, and Neopharm; a research grant to their institution from Merck Sharp & Dohme, and was an advisory board member for Merck Sharp and Dohme, VBL Therapeutics, and Clovis Oncology. PS received research support from Merck and participated in advisory boards for BMS, AstraZeneca, Janssen, and Novartis. MG received speaker's bureau–advisory board fees from Amgen, and received advisory board fees (institutional) from from AstraZeneca, Bristol Myers Squibb, Gilead Sciences, Merck, Novartis, Pfizer, and Takeda Oncology, and travel fees from F Hoffmann-La Roche. VS was a consultant or advisory board member for GlaxoSmithKline and Merck. VC received a grant to institution from AstraZeneca, Bayer, Bayer Healthcare, Bristol Myers Squibb, Merck, Seagen; consultant–advisory board fees from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Merck, Pfizer Canada, and Seagen; and consultant fees from AstraZeneca Canada and Pfizer Canada. CT, KL, AMN, and MJM are employees of Merck Sharp & Dohme and own stock in Merck. NC reports fees for advisory board membership from AstraZeneca, Clovis Oncology, Eisai, GlaxoSmithKline, Immunogen, Mersana, Merck Sharp & Dohme–Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche; fees as an invited speaker for AstraZeneca, Novartis, Clovis Oncology, GlaxoSmithKline, and Merck–Merck Sharp & Dohme; institutional research grants from AstraZeneca, PharmaMar, and Roche; and non-remunerated activities as member of the ESMO Guidelines Steering Committee and chairs for of the Scientific Committee of Alleanza contro il tumore ovarico. DL was a consultant for Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Gynecological Cancer InterGroup, Merck Sharp and Dohme, Pharma Mar; received a research grant to institution from AstraZeneca, Clovis Oncology, F Hoffmann-La Roche, Genmab, GlaxoSmithKline, ImmunoGen, Incyte Corporation, Merck, Merck Sharp and Dohme, PharmaMar; and was a data and safety monitoring board member for Novartis. MVC, EY, MOHdM, and AA declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Monk Bradley, J., et al. (2023). "Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial." The Lancet. Oncology 24(12): 1334-1348.
	Background: Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30-40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer.; Methods: The CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2-IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m 2 ) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5-30 Gy or low-dose/pulse-dose rate, 35-40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866.; Findings: Between Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41-57]). Median follow-up was 18·5 months (IQR 13·2-21·5) in the durvalumab group and 18·4 months (13·2-23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached-not reached) for either group (HR 0·84; 95% CI 0·65-1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3-80·0) with durvalumab and 73·3% (68·4-77·5) with placebo. The most frequently reported grade 3-4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy).; Interpretation: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care.; Funding: AstraZeneca.; Competing Interests: Declaration of interests BJM reports institutional research funding from Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer Advaxis, AstraZeneca, ImmunoGen, Regeneron, and Nucana. Honoraria fr m Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, TESARO/GKS, Vascular Biogenics, GOG Foundation, Elevar Therapeutics, Novocure, Gradalis, Karyopharm Therapeutics, Bayer, EMD Merck, Macrogenics, Sorrento Therapeutics, US Oncology, and Myriad Pharmaceuticals; a leadership position for US Oncology; speakers’ bureau participation for Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, TESARO/GSK, and Merck; served in a consulting or advisory role for Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Myriad Pharmaceuticals, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, TESARO/GSK, Vascular Biogenics, Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, Novocure, Bayer, Elevar Therapeutics, EMD Merck, Gradalis, and US Oncology. TT reports personal fees from AstraZeneca, Chugai, JGOG, and Zeria, outside the submitted work. JCVL reports funding, provision of study material, medical writing, and processing charges for the present work and grants from AstraZeneca; consulting fees and honoraria from AstraZeneca and Bristol Myers Squibb outside the submitted work; travel support from AstraZeneca, Merck Sharp and Dohme, Novartis, and Pfizer; served as an advisor for AstraZeneca; grants for clinical research from AstraZeneca, Bristol Myers Squibb, Janssen, Merck Sharp and Dohme, Novartis, Roche, and Sanofi, outside the submitted work. RS-F received an institutional research grant from Merck Sharp and Dohme and served at an advisory board for Merck Sharp and Dohme; and received lecture honoraria from AstraZeneca, Bristol Myers Squibb, Medison, Merck Sharp and Dohme, Neopharm, Novartis, and Roche, outside the submitted work. UM reports institutional grants from Varian Medical Systems and was a RT Steering Committee member for CALLA study. MdPED reports institutional funding from AstraZeneca for the present work and served as an advisor for AstraZeneca, outside the submitted work. SL has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events and participated on a data safety monitoring board or advisory board for AstraZeneca, Bristol Myers Squibb Boehringer Ingelheim, Merck, Roche, and Novartis, and has a leadership or fiduciary role for Iylon Precision Oncology. FJRG reports support for the present work from AstraZeneca, grants from AstraZeneca, Janssen, Lilly Company, Merck Sharp and Dohme, Roche, and Sanofi; travel support from BioGentec, and an unpaid leadership role with the Comite de Etica e Investigacion del Hospital Civil de Guadalajara, outside the submitted work. NV reports personal research funding from AstraZeneca, Merck Sharp and Dohme, and Roche; Consulting fees or honoraria from Tecnofarma, MSD, and Roche; and is currently the Vice President of the Peruvian Mastology society, outside the submitted work. DA reports funding for this clinical trial was made to his institute from AstraZeneca; an institutional grant from Takeda Pharmaceutical; consulting fees from AbbVie; honoraria from AstraZeneca, AbbVie, MSD, Takeda Pharmaceutical, and Chugai; participated in an advisory board for Takeda Pharmaceutical, AstraZeneca, and MSD; and was the president of the Asian Society of Gynecologic Oncology, the Chairperson of the Japan Society of Gynecologic Oncology, and the Vice President of the Japan Gynecologic Oncology Group. ML reports grants for clinical research from AstraZeneca, Bristol Myers Squib, Merck Sharp and Dohme, and Roche; consulting fees, honoraria, and travel support from Roche, outside the submitted work. J-YL reports personal research funding from AstraZeneca and Merck Sharp and Dohme; institutional funding from Clovis Oncology, Immunogen, Janssen Oncology, Merck, Merck Sharp and Dohme, and Synthon; served an advisory role for AstraZeneca, Merck Sharp an Dohme, Roche, and Takeda. FR reports personal fees from AstraZeneca. YR reports subcontract funding from NIH SBIR grant R44CA254844, compensation from Medical Physics Journal Editorial as the Deputy Editor, and personal fees from AstraZeneca for case review. SW is an employee and shareholder at AstraZeneca and has patents at GlaxoSmithKline UK Ltd and AstraZeneca. AL and HD are employees and shareholders at AstraZeneca. ATN received medical writing support for this manuscript funded by AstraZeneca, is a shareholder and was an employee of AstraZeneca during this study; and is a current employee at Merck. JM reports honoraria and consulting fees from AstraZeneca, Varian Medical Systems, Merck, Primmune, Agenus Bio; grants from NRG Oncology; royalties from Springer Medical Books for published work; and support for attending meetings and travel from NRG Oncology. XW, RT, MM, QZ, COK, SV, RS, YK, W-FC, and GK have nothing to disclose. (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Montana University, o. (2024). Understanding the Role of Doulas in Supporting People With PMADs.
	No Results Available Behavioral: Standard Doula Care Plus PMAD Intervention|Behavioral: Standard Doula Care The Childbirth Self-Efficacy Inventory (CBSEI)|Change in the Childbirth Self-Efficacy Inventory (CBSEI) at 1 month postpartum|Change in the Childbirth Self-Efficacy Inventory (CBSEI) at 3 months postpartum|Change in the Childbirth Self-Efficacy Inventory (CBSEI) at 6 months postpartum|The General Self-Efficacy Scale (SGSE)|Change in the General Self-Efficacy Scale (SGSE) at 1-month postpartum|Change in the General Self-Efficacy Scale (SGSE) at 3-months postpartum|Change in the General Self-Efficacy Scale (SGSE) at 6-months postpartum|Edinburgh Depression Scale|Change in the Edinburgh Depression Scale at 1-month postpartum|Change in the Edinburgh Depression Scale at 3-months postpartum|Change in Edinburgh Depression Scale at 6-months postpartum|Patient Health Questionnaire (PHQ)-9|Change in Patient Health Questionnaire at 1-month postpartum (PHQ)-9|Change in Patient Health Questionnaire at 3-months postpartum (PHQ)-9|Change in Patient Health Questionnaire at 6-months postpartum (PHQ)-9|Generalized Anxiety Disorder (GAD)-7|Change in Generalized Anxiety Disorder (GAD)-7 at 1-month postpartum|Change in Generalized Anxiety Disorder (GAD)-7 at 3-months postpartum|Change in Generalized Anxiety Disorder (GAD)-7 at 6 months postpartum|Multi-Dimensional Scale of Perceived Social Support (MSPSS)|Change in Multi-Dimensional Scale of Perceived Social Support (MSPSS) at 1-month postpartum|Change in Multi-Dimensional Scale of Perceived Social Support (MSPSS) at 3-months postpartum|Change in Multi-Dimensional Scale of Perceived Social Support (MSPSS) at 6-months postpartum|Social Support Questionnaire (SSQ)- Short Form|Change in Social Support Questionnaire (SSQ)- Short Form at 1-month postpartum|Change in Social Support Questionnaire (SSQ)- Short Form at 3-months postpartum|Change in Social Support Questionnaire (SSQ)- Short Form at 6-months postpartum|Birth Companion Support Questionnaire|Change in Birth Companion Support Questionnaire at 3-months postpartum|Change in Birth Companion Support Questionnaire at 6-months postpartum|The Perceived Wellness Scale|Change in the Perceived Wellness Scale at 1-month postpartum|Change in the Perceived Wellness Scale at 3-months postpartum|Change in the Perceived Wellness Scale at 6-months postpartum|City Birth Trauma Scale City Birth Trauma Scale|Change in the City Birth Trauma Scale at 3-months postpartum City Birth Trauma Scale|Change in the City Birth Trauma Scale at 6-months postpartum City Birth Trauma Scale|Alcohol Use Disorders Identification Test (AUDIT) Alcohol Use Disorders Identification Test (AUDIT)|Change in the Alcohol Use Disorders Identification Test (AUDIT) at 1-month postpartum Alcohol Use Disorders Identification Test (AUDIT)|Change in the Alcohol Use Disorders Identification Test (AUDIT) at 3-months postpartum Alcohol Use Disorders Identification Test (AUDIT)|Change in the Alcohol Use Disorders Identification Test (AUDIT) at 6-months postpartum Alcohol Use Disorders Identification Test (AUDIT)|Drug Abuse Screening Test (DAST)|Change in the Drug Abuse Screening Test (DAST) at 1-month postpartum|Change in the Drug Abuse Screening Test (DAST) at 3-months postpartum|Change in the Drug Abuse Screening Test (DAST) at 6-months postpartum|CDC Health-Related Quality of Life (HRQOL)- 4 scale|Change in the CDC Health-Related Quality of Life (HRQOL)- 4 scale at 1-month postpartum|Change in the CDC Health-Related Quality of Life (HRQOL)- 4 scale at 3-months postpartum|Change in the CDC Health-Related Quality of Life (HRQOL)- 4 scale at 6-months postpartum|Pregnancy Risk Assessment Monitoring (PRAMS) Female Not Applicable 75 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Health Services Research 162-22 February 2025

Montegut, C., et al. (2021). "Safety and quality of life of first-line maintenance olaparib plus bevacizumab in older patients with advanced ovarian cancer in the paola-1 trial." International Journal of Gynecological Cancer 31(SUPPL 1): A201‐A202.
	Introduction/Background The Phase III PAOLA‐1/ENGOTov25 study (NCT02477644) demonstrated that the addition of olaparib to bevacizumab maintenance following standard platinum‐based therapy plus bevacizumab improved progression‐ free survival (PFS) in patients with newly diagnosed advanced ovarian cancer (Ray‐Coquard et al. NEJM 2019). We aimed to describe safety, quality of life (QoL), and efficacy with olaparib plus bevacizumab in patients ≥70 years old. Methodology Safety (adverse events [AEs] graded according to CTCAE v5.0) and QoL (measured using EORTC QLQ‐C30 global health status [GHS]) data were collected. We compared safety by age (older [≥70 years] and younger patients [<70 years]) in the olaparib arm. Geriatric features, including Geriatric Vulnerability Score (GVS; Falandry et al. Ann Oncol 2013) items, and QoL by treatment arm were assessed in older patients. years old; 104 of these were in the olaparib arm. There was no notable difference in baseline characteristics between olaparib and placebo arms (table 1). In evaluation of safety, moderately increased rates of grade ≥3 treatment‐related AEs (TRAEs), dose reductions and interruptions, and treatment discontinuation due to TRAEs were reported in older than younger patients (table 2). Grade 3‐4 any‐cause anaemia (21.2% vs 16.5%) and neutropenia (9.7% vs 5.1%) were more frequent in older patients. The most common grade 3‐4 non‐haematological AE was hypertension (26.9% vs 16.7%). No acute myeloid leukaemia, myelodysplastic syndrome, or treatment‐related death was reported among older patients. Interestingly, GHS during the first 2 years of maintenance was similar between arms. Median PFS was 21.1 months with olaparib vs 14.3 months with placebo. Analyses by GVS and homologous recombination deficiency subgroups are ongoing and will be presented. Conclusion Among older patients in PAOLA‐1, olaparib plus bevacizumab maintenance had a manageable safety profile and had no adverse impact on GHS. Median PFS in older patients was similar to the overall population. Analyses stratified by GVS will provide further insight into the safety profile of maintenance olaparib plus bevacizumab in older patients.

Monteiro, F., et al. (2022). "Cost-utility of a web-based intervention to promote maternal mental health among postpartum women presenting low risk for postpartum depression." International journal of technology assessment in health care 38(1): e62.
	Objectives: Web-based interventions for the promotion of maternal mental health could represent a cost-effective strategy to reduce the burden associated with perinatal mental illness. This study aimed to evaluate the cost-utility of Be a Mom, a self-guided web-based cognitive behavioral therapy intervention, compared with a waiting-list control.; Methods: The economic evaluation alongside a randomized controlled trial was conducted from a societal perspective over a 14-month time frame. Postpartum women presenting low risk for postpartum depression were randomized to the intervention ( n = 191) or control ( n = 176) group and assessed at baseline, postintervention and 4 and 12 months after postintervention. Data regarding healthcare use, productive losses and quality-adjusted life years (QALYs) were collected and used to calculate incremental cost-effectiveness ratios (ICERs). Uncertainty was accounted for with nonparametric bootstrapping and sensitivity analyses.; Results: At 14 months, and after accounting for a 3.5 percent discount rate, the intervention resulted in a yearly cost-saving of EUR 165.47 (-361.77, 28.51) and a QALY gain of 0.0064 (-0.0116, 0.0244). Bootstrapping results revealed a dominant ICER for the intervention group. Although results were statistically nonsignificant, cost-effectiveness acceptability curves showed that at a EUR 0 willingness to pay threshold, there is a 96 percent probability that the intervention is cost-effective when compared with the control group. The sensitivity analyses generally supported the acceptable likelihood of the intervention being more cost-effective than the control group.; Conclusions: From a societal perspective, the implementation of Be a Mom among low-risk postpartum women could be a cost-effective way to improve perinatal mental health.

Monteiro, F., et al. (2021). "Be a Mom, a Web-Based Intervention to Promote Positive Mental Health Among Postpartum Women With Low Risk for Postpartum Depression: Exploring Psychological Mechanisms of Change." Frontiers in Psychiatry 12: 701107.
	Background: This study explored whether Be a Mom, a brief and unguided cognitive behavioral web-based intervention, was effective in promoting psychological processes (self-compassion, psychological flexibility, emotion regulation) among low-risk postpartum women. Effects of Be a Mom in psychological processes compared with a control group were examined at post-intervention and at 4-months follow-up. Additionally, this work explored whether changes in psychological processes mediated improvements in positive mental health at postintervention. Methods: In total, 367 postpartum women presenting low risk for postpartum depression were randomly assigned to the intervention group (n = 191) or to a waiting-list control group (n = 176). Results: Compared with the control group, the intervention group reported significantly greater baseline to postintervention increases in self-compassion. No significant effects were found at the 4-month follow-up. Multilevel mediation showed that self-compassion improvements significantly mediated improvements in positive mental health among the intervention group. No significant results were found for psychological flexibility or emotion regulation. Conclusions: This study suggests that Be a Mom has the potential to cultivate self-compassion among low-risk postpartum women and that this may be a key mechanism for promoting positive mental health in this context. Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT04055974.

Monteiro, F., et al. (2022). "Be a Mom's efficacy in enhancing positive mental health among postpartum women presenting low risk for postpartum depression: Results from a pilot randomised trial." Journal of Reproductive and Infant Psychology 40(2): li.
	Background The promotion of positive mental health and flourishing during the postpartum period has been neglected in detriment of a single focus on prevention and treatment of mental illness. Be a Mom is a self-guided web-based intervention that was developed to promote maternal mental health among postpartum women. Aims and Objectives The primary aim of this study was to conduct a preliminary investigation of the efficacy of Be a Mom in enhancing positive mental health among postpartum women at low risk for postpartum depression (PPD). We also aimed to evaluate Be a Mom's efficacy regarding secondary outcomes (depressive and anxiety symptoms, maternal self-efficacy, empowerment, relationship satisfaction). Methods A pilot randomised, two-arm controlled trial was conducted. Women were eligible to participate if they were in the early postpartum period (up to 3 months postpartum) and presented no risk factors for PPD (Postpartum Predictors Inventory-Revised < 5.5). A total of 367 participants were randomly assigned to the Be a Mom group (n = 191) or to the waiting-list control group (n = 176) and completed baseline (T1) and post-intervention (T2) assessments. Results Significant time and group effects were found for positive mental health, with participants in the intervention group reporting significant increases in positive mental health between T1 and T2 compared to participants in the control group. A significantly higher proportion of participants in the Be a Mom group had an improvement trajectory (from not flourishing at T1 to flourishing at T2). No significant time and group effects were found for the remaining secondary outcomes. Interpretation/Discussion This study provides preliminary evidence supporting the efficacy of Be a Mom in increasing positive mental health and flourishing among low-risk postpartum women. Conclusions Our findings support mental health promotion strategies in the postpartum period and highlight the important role of web-based CBT interventions.

Monteiro, M. G. C. T. and G. P. de Morais Gouveia (2021). "Physiotherapy in the management of gynecological cancer patient: A systematic review." Journal of Bodywork and Movement Therapies 28: 354-361.
	Aim: to evaluate the effectiveness of physiotherapy as an adjunct treatment in patients with gynecological cancer. Method(s): systematic review carried out in the PubMed, MEDLINE, via VHL, Cochrane and SciELO, in the last ten years. A search strategy was based on the PICO method and the PRISMA flowchart using Boolean descriptors and operators: "gynecological cancer or neoplasms of female genital organs" and "physiotherapy or physiotherapy modalities" and "rehabilitation or quality of life" in languages Portuguese, English, and Spanish. Result(s): 405 articles were found, and after eligibility criteria, only 5 studies were selected for review. Evidence of a monitored physical exercise, photobiomodulation and pelvic floor rehabilitation program as physiotherapeutic resources in the management of gynecological cancer. Conclusion(s): Physiotherapy dominates techniques and appears to be beneficial for the main complications arising from the treatment or post-treatment of gynecological cancer and has sought to accompany the knowledge and care of the patient, through scientific research.Copyright © 2021 Elsevier Ltd

Monteiro, S., et al. (2023). "Bladder training compared to bladder training associated with pelvic floor muscle training for overactive bladder symptoms in women: A randomized clinical trial." Neurourology and Urodynamics 42(8): 1802-1811.
	Aims: To compare the effects of bladder training (BT) versus BT with pelvic floor muscle training (PFMT) in women with overactive bladder (OAB) symptoms. Method(s): Randomized controlled clinical trial including women with OAB symptoms, randomized into two groups: BT versus BT + PFMT. For 12 consecutive weeks, the women received home BT. The BT + PFMT performed supervised PFMT, once/week, associated at home PFMT protocol. Primary outcomes were urinary urgency, daytime voiding frequency, nocturia and urgency urinary incontinence assisted by both 3-day bladder diary and International Consultation on Incontinence OAB (ICIQ-OAB) questionnaire. Secondary outcomes were 24-h pad test and Patient Global Impression of Improvement. T-test, analysis of variance, Mann-Whitney (SPSS 20.0) and power/effect size (G-power) were applied in data analyses. Result(s): Sixty-three women were included (B = 31; BT + PFMT = 32). There was no significant statistical difference between groups in terms of urinary symptoms: daytime frequency (BT: pre: 11.59 [+/-5.80], post: 9.10 [+/-4.05]; BT + PFMT: pre: 10.67 [+/-3.73], post: 8.08 [+/-3.38]) p = 0.75; nocturia: (BT: pre: 1.46 [+/-0.91], post: 0.82 [+/-0.82]; BT + PFMT: pre: 1.80 [+/-2.26], post: 0.82 [+/-1.15]) p = 0.70; urinary urgency (BT: pre: 3.22 [+/-4.70], post: 4.49 [+/-4.32]; BT + PFMT: pre: 6.87 [+/-5.60], post: 6.15 [+/-4.52]) p = 0.10; ICIQ-OAB total score: (BT: pre: 9.16 [+/-2.55], post: 6.32 [+/-3.77]; (BT + PFMT: pre: 9.75 [+/-2.06], post: 5.06 [+/-3.44] p = 0.30. Conclusion(s): Supervised PFMT added to BT did not provide further improvements than isolated BT in women with OAB symptoms.Copyright © 2023 Wiley Periodicals LLC.

Montera, R., et al. (2023). "Efficacy of termoablative fractional CO2 laser (Monnalisa Touch) in stress urinary incontinence." Neurourology and Urodynamics 42(2): 393-400.
	Purpose: Usually, in stress urinary incontinence (SUI), nonsurgical therapy such as pelvic floor muscle training (PFMT) and lifestyle changes are proposed before surgical treatment. Laser therapy has recently been recommended for the treatment of SUI, helping to reconstruct the collagen that supports the vagina and the pelvic floor. The aim of the study was to evaluate the efficacy of SUI treatment with a CO2 intravaginal laser in patients waiting for anti-incontinence surgery (TVT-O). Method(s): This is a prospective, case-control study. Fifty-two patients have been included in our study and we divided them into two groups: atrophy and no atrophy. We also adopted a control group retrospectively identified from our database of patients undergoing PFMT. The subjective estimation of SUI symptoms before and after treatment was evaluated using the Visual Analog Scale before and after 1, 6, and 12 months of treatment. The objective evaluation with the urodynamic study with the stress test and a 3-day voiding diary to count the number of episodes of incontinence, before and after treatment. Result(s): The intravaginal CO2 laser improved all the parameters considered for SUI in both groups. Its results were more relevant in the atrophy group, in comparison to the no atrophy group, even if they were both statistically significant. There were no statistically significant differences for all the parameters evaluated for SUI between laser treatment and PFMT in the control group. Conclusion(s): The CO2 laser is well-tolerated, minimally invasive, safe, and showing efficacy for SUI. More studies are needed to consider it as first-instance therapy, like PFMT, or at least, as a bridge therapy to surgery.Copyright © 2022 Wiley Periodicals LLC.

Montera, R., et al. (2023). "The use of sealing hemostat patch (HEMOPATCH ® ) in laparotomic myomectomy: a prospective case-control study." Archives of Gynecology and Obstetrics 307(5): 1521-1528.
	Purpose: Uterine myomas are the most common gynecological disease. In these cases, a myomectomy is performed traditionally laparotomically. However, alternatives have been widely used, including laparoscopic, endoscopic, and robotic surgery. During these techniques, diffuse parenchymatous bleeding remains one of the main intraoperative and postoperative complications and sometimes requires unplanned hysterectomies. Recently, hemostatic agents and sealants have been used to prevent excessive blood loss during surgical repair.; Methods: We propose a prospective case-control study on the use of a sealing hemostat patch (HEMOPATCH ® ) on uterine sutures in laparotomic myomectomy. In the period between July 2016 and April 2017, 46 patients with symptomatic uterine fibromatosis underwent surgery. They were divided into two groups of 23 patients, with different treatments in the hemostatic phase of oozing bleeding. HEMOPATCH ® is applied in group A, and spray electrocoagulation is applied in group B.; Results: In group A, we achieve faster hemostasis (p < 0.05), than in group B. We report a significantly lower C-reactive protein value on the second and third days after surgery for group A compared to group B.; Conclusions: HEMOPATCH ® , during laparotomic myomectomy, is a valid alternative solution for obtaining rapid hemostasis and consequently intraoperative and postoperative bleeding. Furthermore, we suggest that a lower inflammatory peritoneal state is probably correlated with the barrier effect of the patch on the suture. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Montero-Macías, R., et al. (2022). "Traditional Systemic Treatment Options in Advanced Low-Grade Serous Ovarian Cancer after Successful Cytoreduction: A Systematic Review and Meta-Analysis." Cancers 14(15).
	Objective: We performed a systematic literature review and a subsequent meta-analysis to compare traditional treatment options, i.e., antihormonal and cytotoxic, in LGSOC.; Methods: We conducted a systematic literature review in MEDBASE and MEDLINE between September 2000 and June 2021 for women who received cytotoxic chemotherapy and/or antihormonal treatment after primary cytoreduction due to stage II-IV LGSOC and also at relapse. PFS and OS were calculated depending on the type of their adjuvant treatment. For each endpoint in the meta-analysis, pooled HR was calculated using the random effect model with the inverse variance weighted method. Only primary patients were included in the subsequent meta-analysis due to the small number of studies in the relapsed setting.; Results: Five eligible first-line studies were included. Systemic chemotherapy failed to provide a significant OS benefit when compared to no systemic treatment (pooled HR = 1.01, 95% CI [0.79, 1.29]) after successful cytoreduction. Moreover, systemic chemotherapy followed by antihormonal treatment also did not result to a significant PFS or OS benefit when compared to systemic chemotherapy alone (for PSF: pooled HR = 0.59, 95% CI [0.33, 1.04]; for OS: pooled HR = 0.83, 95% CI [0.50, 1.39]). There were insufficient data from studies in the recurrent setting to allow their inclusion in the meta-analysis.; Conclusions: In this meta-analysis, we failed to identify a traditional cytotoxic or antihormonal systemic treatment option that was associated with a significant OS or PFS benefit when administered following successful cytoreduction for advanced LGSOC. Prospective randomized studies are urgently warranted to define optimal adjuvant options in this challenging disease.

Mooij, R., et al. (2021). "[Complications related to pessary use in the treatment of female pelvic organ prolapse]." Nederlands tijdschrift voor geneeskunde 165.
	Pelvic organ prolapse affects 40% of women over 40 years. Pessaries are often used as a first-line treatment and give high patient satisfaction. Complications of pessaries are rare, but vaginal erosions can lead to adhesions, haemorrhage, impaction and migration. This year we have seen an increase in pessary complications in our hospital after check-ups were postponed. In this article, we present a case of a complication of a vaginal pessary after the postponement of a follow-up visit in the COVID-19 era. An 85-year old woman had a pessary which had migrated into the bladder, 8 months after her last check-up. The fistula was repaired and a new pessary could be fitted after 6 weeks. Vaginal erosions can be prevented by good fitting, local estrogens and self-management. Early detection can be achieved with careful follow-up and patient education. Erosions can be treated with local estrogens and temporary removal of the pessary.

Moon, A., et al. (2021). "Surgical site infiltration versus transversus abdominis plane block of liposomal bupivacaine after midline vertical laparotomy for gynecologic malignancy: a prospective randomized controlled trial." International Journal of Gynecological Cancer 31(SUPPL 4): A130.
	Objectives Surgical site infiltration (SSI) and transversus abdominis plane (TAP) block are postoperative analgesic techniques. Liposomal bupivacaine may prolong analgesic effects. We hypothesize that surgical site infiltration of liposomal bupivacaine will reduce opioid consumption in the 48‐hour postoperative period compared to TAP block. Methods A single blind randomized controlled trial comparing surgical site infiltration of liposomal bupivacaine versus TAP block with liposomal bupivacaine after midline vertical laparotomy in patients with suspected or known gynecologic malignancy. Negative binomial regression was used to estimate the differences in total morphine milligram equivalent (MME) use between groups. Multivariable linear regression of pain scores on visual analog scale 0‐10 was used at each time interval (2, 6, 12, 24, and 48 hours postoperatively) while controlling for medication use and age. Results Of 43 patients, 22 received SSI and 21 received TAP block. Mean age was 57.8 (SD = 11.50). There were no significant differences in demographics, incision length, surgery duration or pathology between groups. After controlling for age and BMI, there was not a statistically significant difference in total MME between the treatment groups (b = ‐0.17, 95% CI = ‐0.77, 0.43, p = 0.59). There were no statistically significant differences in pain scores (both resting and exertion) at all time points after controlling for age and pain medication utilization. Conclusions Surgical site infiltration of liposomal bupivacaine did not reduce opioid use and did not decrease pain scores within 48 hours after surgery compared to TAP block after midline vertical laparotomy for gynecologic cancer.

Moon, J. (2022). "Resectable cervical esophageal cancer : Surgery or definitive chemoradiotherapy with dose escalation." Radiotherapy and Oncology 170(Supplement 1): S440-S441.
	Purpose or Objective Cervical esophageal cancer is rare subgroup for 5% to 10% of all esophageal cancers. Most of patients of cervical esophageal cancer needed hypopharyngectomy and laryngectomy for complete resection, and definitive CRT has been widely accepted treatment of choice for laryngeal preservation. There are few evidence studies have compared treatment outcomes between surgery and CRT in cervical esophageal cancer. Hence, we reviewed our institutional experiences to compare and tried to suggest the appropriate treatment directions for resectable cervical esophageal cancer. Materials and Methods A total of 197 patients were diagnosed as cervical esophageal cancer without distant metastasis between January 2001 and December 2020. Of those, 47 patients were excluded in this study because of unresectable stage (e.g. initial stage T4 or extensive nodal stage). Consequently, 100 patients had definitive chemoradiotherapy and 50 patients had surgery. In surgery group, 16 patients received preoperative treatment (CRT; 6 patients, CTx alone; 10 patients) and 16 patients received postoperative treatment (CRT; 6 patients, CTx alone, 6 patients, radiotherapy alone; 4 patients). Definitive CRT group patients received 5-fluorouracil/cisplatin based chemotherapy concurrently and were divided into high-dose group (>=59.4 Gy, n=71), and standard dose group (<59.4 Gy, n=29). Results The median follow-up was 30 months (5-225 months) for surviving patients. Of 50 patients with median age 63 in surgery group, 21 (42%), 9 (18%), 18 (36%), 2 (4%) patients were stage I, II, III and IV respectively. In contrast, patients in CRT group was statistically significant different in age (median 67) and stage as 19 (19%), 30 (30%), 44 (44%), 7 (7%) patients were stage I, II, III, IV. There was no statistically difference between CRT group and surgery group in overall survival(OS) (3 year OS : 61.2% vs 62.9%, p=0.976 ) and progression free survival (PFS) (3 year PFS : 47.5 % vs 53.0%, p=0.589). Treatment related toxicity (Grade>=2) were significant higher in surgery group than CRT group (14(28%) vs 12 (12%), p=0.015), even only 6 patients received hypopharyngectomy and laryngectomy. In subgroup analysis between high-dose group and standard dose group, OS and loco-regional failure free survival (LRFS) was significantly higher in high-dose group (3 year OS : 65.4% vs 51.7%, p=0.046, 3 year LRFS 68.7% vs 42.5%). Conclusion There was no significant difference in OS and PFS between surgery and CRT group although surgery group had patient selection bias for patients with earlier stage and younger age. Also, LRFS were better with high-dose CRT than standard group which lead to better OS and consequently achieved favor OS in general CRT group. High dose RT was not associated with higher toxicity rate, mainly because recent intensity modulated RT could give higher dose while saving normal organ toxicity. Thus, high dose CRT should be considered as initial treatment for cervical esophagus than surgery.Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Moon, J. Y. (2022). "Treatment of Choice for Resectable Cervical Esophageal Cancer: Surgery and Definitive Chemoradiotherapy with or without Dose Escalation." International journal of radiation oncology biology physics 114(3 Supplement): e164.
	Purpose/Objective(s): Cervical esophageal cancer is rare subgroup which epicenter of tumor located between upper esophageal sphincter and sternum notch, for 5% to 10% of all esophageal cancers. Most of patients of cervical esophageal cancer needed hypopharyngectomy and laryngectomy for complete resection, pre-operative chemotherapy (CTx) or chemoradiotherapy (CRT) is needed, and even definitive CRT has been widely accepted treatment of choice for laryngeal preservation. We reviewed our institutional experiences to compare and tried to suggest the treatment directions for resectable cervical esophageal cancer. Materials/Methods: A total of 197 patients who were diagnosed as cervical esophageal cancer without distant metastasis between January 2001 and December 2020 were identified. Of those, 47 patients were excluded in this study because of unresectable stage (e.g., initial stage T4 or extensive nodal stage), 100 patients had definitive chemoradiotherapy and 50 patients had surgery. In surgery group, 16 patients received preoperative treatment (CRT; 6 patients, CTx alone; 10 patients) and 16 patients received postoperative treatment (CRT; 6 patients, CTx alone, 6 patients, radiotherapy alone; 4 patients). Definitive CRT group patients were divided into high-dose group (>=59.4 Gy, n=71), and standard dose group (<59.4 Gy, n=29). Result(s): The median follow-up was 30 months (5-225 months) for surviving patients. Of 50 patients with median age 63 in surgery group, 21 (42%), 9 (18%), 18 (36%), 2 (4%) patients were stage I, II, III and IV respectively. Patients in CRT group was statistically significant different in age (median 67) and stage as 19 (19%), 30 (30%), 44 (44%), 7 (7%) patients were stage I, II, III, IV. There was no statistical difference in overall survival (OS) (3-year OS: 61.2% vs 62.9%, p=0.976) and progression free survival (PFS) (3-year PFS: 47.5 % vs 53.0%, p=0.589). Treatment related toxicity (Grade>=2) were significantly higher in surgery group than CRT group (14(28%) vs 12 (12%), p=0.015), even only 6 patients received hypopharyngectomy and laryngectomy. In subgroup analysis between high-dose group and standard dose group, OS and loco-regional failure free survival (LRFS) was significantly higher in high-dose group (3-year OS: 65.4% vs 51.7%, p=0.046, 3-year LRFS 68.7% vs 42.5%). There was no significant difference between two group (High-dose group 9 (12.7%) vs Standard dose group 3 (10.3%), p=0.106). Conclusion(s): There was no significant difference in OS and PFS between surgery and CRT group although surgery group had patient selection bias for patients with earlier stage and younger age. Also, LRFS were better with high-dose CRT than standard group which lead to better OS and consequently achieved favor OS in general CRT group. High dose RT was not associated with higher toxicity rate, mainly because recent intensity modulated RT could give higher dose while saving normal organ toxicity. Thus, high dose CRT should be considered as initial treatment for cervical esophagus than surgery.Copyright © 2022

Mooney, K., et al. (2022). "A randomized control trial to determine necessary intervention elements to achieve optimal symptom outcomes for a remote symptom management system." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Interventions to improve patient-reported cancer symptom outcomes (PROs) are often multicomponent. In order to scale efficacious interventions, it is important to know if all components are needed to achieve the greatest benefit. We deconstructed the Symptom Care at Home (SCH) monitoring and management system, a multicomponent intervention found to be highly efficacious in reducing symptom burden for patients at home. SCH remotely monitors daily PROs, provides tailored automated self-management coaching based on the severity pattern reported for 11 monitored symptoms and alerts a nurse practitioner (NP) of poorly controlled moderate to severe symptoms. The NP follows up to intensify symptom care utilizing the SCH decision support system based on national guidelines. Method(s): A 5 group randomized controlled design was utilized with 755 participants assigned to PRO assessment plus: Gp 1, (N = 143) automated self-management coaching, Gp 2, (N = 144) automated self-management coaching plus an activity tracker, Gp 3, (N = 147) NP follow up without decision support, Gp 4, (N = 154) NP follow up utilizing decision support or Gp 5, (N = 167) automated coaching plus NP follow up utilizing decision support- the complete SCH intervention. The primary outcome was maximum likelihood estimation of overall symptom severity over the duration of study participation (62 day median). Result(s): Patients were recruited from sites in Utah and Georgia. The majority of patients were female (60.3%), married (59.9%), 60.7% Caucasian and 34.9% Black, with a mean age of 59.4 years and Stage 3 or 4 cancer (65.7%). Most common diagnoses included breast (17.1%), lung (13.9%), colorectal (12.9%), pancreatic (8.6%) and ovarian (8.4%). Adherence rate for daily symptom reports was 73.8% with no differences between groups. 84.2% of patients reported one or more moderate or severe symptoms- most commonly fatigue (70.1%), pain (64.8%) and trouble sleeping (56.0%). Group 5- the complete SCH intervention had significantly greater symptom relief than any other group (Gp 5 vs Gp 1 or Gp 2 automated coaching both p <.001; Gp 5 vs Gp3 NP without decision support p =.039; Gp 5 vs Gp 4 NP with decision support p =.017). The two NP groups did not differ significantly but were significantly better than either automated coaching groups. The two automated coaching groups did not differ significantly from one another. Conclusion(s): PRO assessment with automated coaching and NP decision-supported follow-up for moderate to severe symptoms achieved better symptom reduction than the individual components. Better symptom relief can be obtained for patients at home through a synergistic, multicomponent intervention that combines a tailored symptom coaching component with notification and follow up by clinicians when symptoms rise to moderate or severe levels- both components contribute to better outcomes.

Mooney Samantha, S., et al. (2022). "Virtual clinics in gynaecology - Can we shorten the wait? A randomised controlled trial implementing a novel care pathway for postmenopausal bleeding." The Australian & New Zealand Journal of Obstetrics & Gynaecology 62(5): 732-739.
	Background: Postmenopausal bleeding (PMB), a common symptom of endometrial cancer, necessitates prompt clinical and sonographic assessment, often followed by hysteroscopy. Unfortunately, due to traditional gynaecology outpatient clinic paradigms, unnecessary patient-clinician encounters are common and may lead to delays in diagnosis.; Aim: The aim was to assess a novel clinic model for the management of women with PMB based on virtual assessment and routine use of the outpatient hysteroscopy clinic.; Methods: An unblinded pragmatic randomised controlled trial was performed, comparing a 'virtual clinic' to routine outpatient clinical care. The primary outcome for assessment was time, measured as the interval (days) between referral triage and discharge for definitive management or to the general practitioner. Demographical and clinical data were collected. After discharge from the system, patients completed a satisfaction and feedback questionnaire. Log-rank tests were used to compare the equality of time-to-event functions across randomised groups.; Results: There were 96 participants, 46 in the intervention arm and 50 controls. The total time spent in the gynaecology system differed between groups (Χ 2 (1) = 6.94, P = 0.008), with a median total time of 55 days (95% confidence interval (CI): 37-66 days) for the intervention group compared to a median of 84 days (95% CI: 54-101 days) for the control group. The number of in-person gynaecology encounters differed between those randomised to intervention (P < 0.001). Overall, 96% of respondents indicated a positive score for overall satisfaction.; Conclusions: The proposed clinic model resulted in a significant reduction in the time between referral and discharge, without compromising patient satisfaction. (© 2022 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Mooney, S. S., et al. (2021). "Obstetric Outcome After Surgical Treatment of Endometriosis: A Review of the Literature." Frontiers in Reproductive Health 3: 750750.
	A diagnosis of endometriosis is associated with increased risks of adverse pregnancy outcomes including placenta praevia and preterm birth. Some studies have also suggested associations with gestational hypertension, foetal growth restriction, gestational diabetes, perinatal death, and obstetric haemorrhage. This review aims to assess the impact of pre-pregnancy surgical treatment of endometriosis on future obstetric outcomes. A search of the Medline, Embase and PubMed electronic databases was performed to identify studies reporting pre-pregnancy surgery for endometriosis and subsequent pregnancy outcome compared to controls with unresected endometriosis. Three studies met the inclusion criteria. The studies were heterogenous in design, definition of study groups and outcome measures. All three studies were judged at critical risk of bias. Pre-pregnancy excision of endometriosis was associated with an increased risk of caesarean section in one of two studies, OR 1.72 (95% CI 1.59-1.86) and OR 1.79 (95% CI 0.69-4.64). Placenta praevia rates were also increased in one of two studies OR 2.83 (95% CI 0.56-12.31) and OR 2.04 (95% CI 1.66-2.52). One study found increased risks of preterm birth, small for gestational age, gestational hypertension, and antepartum and postpartum haemorrhage (all p < 0.05) with pre-pregnancy excision of endometriosis. There is insufficient evidence examining the role of pre-pregnancy endometriosis surgery in ameliorating adverse pregnancy outcomes, and thus reliable conclusions cannot be drawn. Prospectively designed studies are needed to assess the relationship between surgical treatments for endometriosis and obstetric outcome and examine potential confounders such as comorbid adenomyosis and infertility.

Moonkum, N., et al. (2023). "A phamtom study: In vivo rectal dosimetry of high dose rate brachytherapy in cervical cancer." Applied Radiation and Isotopes 192: 110604.
	The purpose of this study was to perform in-vivo dosimetry using a diode rectal dosimeter in phantom and compare the dose delivered to the rectum between the dose measured by the diode dosimeter and the dose calculated by the treatment planning system in cervical cancer. The PTW T9112 diode detector calibrations were performed to find the correction factor. Then the calibrated diode detector was used to measure the radiation dose received in the rectum area in the in-house pelvic phantom. An Iridium-192 source was loaded into the phantom with 7 Gy, the measurements were 3 times per treatment plan, with 15 total plans studied. The average cumulative charge (nC) of each plan was converted to the absorbed dose (mGy) for comparison with the treatment planning system. Finally, to test the hypothesis that an absorbed dose from the detector and the treatment planning system were not significantly different, dependent t-test statistical analysis was applied with p-value <0.05. For distance and direction correction factors, we found that the factors were approximately 1 at 5 cm and 180degree. The percentage differences of radiation dose between the diode dosimeter and the treatment planning system were between -3.3 and 4.1%. Statistical analysis revealed that the doses from the detector and the treatment planning system were not statistically significant different. The comparison showed that the percent difference between diode dosimeter and treatment planning system was acceptable to perform the in vivo dosimetry in brachytherapy. Therefore, the diode detector may be a suitable candidate for a treatment verification system in cervical cancer brachytherapy to prevent the dose delivery errors that directly affect the prognosis and may cause complications for the patient.Copyright © 2022 Elsevier Ltd

Moore, B., et al. (2021). "History and scientific background on the economics of abortion." PloS One 16(9): e0257360.
	Background: Approximately one quarter of all pregnancies globally end in abortion, making it one of the most common gynecological practices worldwide. Despite the high incidence of abortion around the globe, the synthesis of known economic outcomes of abortion care and policies is lacking. Using data from a systematic scoping review, we synthesized the literature on the economics of abortion at the microeconomic, mesoeconomic, and mesoeconomic levels and presented the results in a collection of studies. This article describes the history and scientific background for collection, presents the scoping review framework, and discusses the value of this knowledge base.; Methods and Findings: We conducted a scoping review using the PRISMA extension for Scoping Reviews. Studies reporting on qualitative and/or quantitative data from any world region were considered. For inclusion, studies must have examined one of the following outcomes: costs, impacts, benefits, and/or value of abortion-related care or policies. Our searches yielded 19,653 unique items, of which 365 items were included in our final inventory. Studies most often reported costs (n = 262), followed by impacts (n = 140), benefits (n = 58), and values (n = 40). Approximately one quarter (89/365) of studies contained information on the secondary outcome on stigma. Economic factors can lead to a delay in abortion care-seeking and can restrict health systems from adequately meeting the demand for abortion services. Provision of post-abortion care (PAC) services requires more resources then safe abortion services. Lack of insurance or public funding for abortion services can increase the cost of services and the overall economic impact on individuals both seeking and providing care.; Conclusions: Consistent economic themes emerge from research on abortion, though evidence gaps remain that need to be addressed through more standardized methods and consideration to framing of abortion issues in economics terms. Given the highly charged political nature of abortion around the world, it is imperative that researchers continue to build the evidence base on economic outcomes of abortion services and regulations.; Competing Interests: The authors have declared that no competing interests exist.

Moore, K., et al. (2023). "FIRST-IN-HUMAN PHASE 1/2 STUDY OF UBAMATAMAB, A MUC16XCD3 BISPECIFIC ANTIBODY, ADMINISTERED ALONE OR IN COMBINATION WITH CEMIPLIMAB IN PATIENTS WITH RECURRENT OVARIAN CANCER." International Journal of Gynecological Cancer 33(Supplement 4): A254-A255.
	Introduction Ubamatamab (REGN4018) is a MUC16xCD3 bispecific antibody that promotes T cell-mediated cytotoxicity by facilitating contact between cancer cells and T cells. In a Phase 1 study (NCT03564340) in patients with recurrent ovarian cancer (OC), ubamatamab monotherapy demonstrated an acceptable safety profile and durable clinical activity at doses of 20 mg to 800 mg IV weekly (by RECIST and CA-125 response rates), and linear pharmacokinetics up to 800 mg IV weekly. Methods In Phase 2, up to 150 patients with advanced platinum- resistant OC and elevated serum CA-125 will be randomized 1:1:1 to IV Q3W treatment: ubamatamab 250 mg; ubamatamab 800 mg; or ubamatamab 250 mg plus cemiplimab 350 mg (figure 1). All treatment arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome before proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with interim analysis after 20 patients. Any arm with >=3 objective responses will be expanded to 50 patients. The primary endpoint for each treatment arm is ORR per RECIST 1.1 criteria. Secondary endpoints include DOR, PFS, safety, and pharmacokinetics of ubamatamab with/without cemiplimab. Exploratory endpoints include evaluation of baseline tumor MUC16 expression and other biomarkers as predictors of response. The impact of ubamatamab on QOL and physical functioning will be assessed. Current Trial Status The study is currently recruiting patients to combination dose escalation, monotherapy dose expansion, and the randomized Phase 2 cohort.

Moore, K., et al. (2022). "MIRASOL: A randomized, open-label, phase 3 study of mirvetuximab soravtansine vs. investigator's choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRalpha) expression (297)." Gynecologic Oncology 166(Supplement 1): S156-S157.
	Objectives: Elevated FRalpha expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising an FRalpha-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has consistently shown clinically meaningful single-agent activity, along with favorable tolerability, in patients with high FRalpha expressing tumors (Moore ESMO 2019). Method(s): MIRASOL is a randomized phase III study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC (including primary peritoneal cancer or fallopian tube cancer). Confirmation of high FRalpha positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; >= 75% of cells with PS2+ staining intensity) and 1-3 prior lines of therapy are required for inclusion. MIRASOL is designed to randomize 430 patients, 1:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators' choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival by investigator, and secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. MIRASOL (GOG 3045/ENGOT-ov55) is a global study that opened for enrollment in December 2019. Clinical trial information: NCT04209855.Copyright © 2022 Elsevier Inc.

Moore, K., et al. (2022). "A Phase II Clinical Trial Design to Assess Intestinal Toxicity Reduction with Adaptive External Beam Radiation Therapy in the Treatment of Cervical Cancer (ARTIA-Cervix)." Medical Physics 49(6): e442.
	Purpose: To decrease acute high-grade gastrointestinal toxicity in external beam radiotherapy (EBRT) in gynecologic cancers, reducing large PTV margins safely with daily adaptive radiotherapy is proposed. ARTIA-Cervix is a single-arm prospective Phase II multi-institutional clinical trial to investigate the effect of adaptive radiotherapy for locally advanced cervical cancer in decreasing the rate of acute gastrointestinal toxicity. We report the rationale, primary objective, and feasibility of this clinical trial. Method(s): The primary objective is to demonstrate that gastrointestinal toxicity associated with adaptive pelvic IMRT (1.8Gy*25=45Gy) is lower than the observed rate for non-adaptive IMRT in node-negative gynecologic cancer (33% patient-reported toxicity on RTOG 1203), as measured by PRO-CTCAE (score>=3) at week 5 of EBRT. Using the Varian EthosTM platform and ARTIA-Cervix protocol-specific autoplanning template, bowel V40Gy and V45Gy for 3-5mm PTV margins vs. current standard-of-care non-adaptive margins (7-15mm) were measured in 21 previously-treated node-negative cervical cancer patients. Time to complete the physicist-driven daily adaptive workflow was measured in 75 mock treatments (15 patients, 5 retrospective CBCTs each). Sample size and statistical power were calculated with the Wilson score interval, assuming 33%-20%=13% effect size for toxicity reduction. Result(s): The pre-planning study showed bowel V40Gy and V45Gy reductions of 252cc->140cc and 167cc->43cc, respectively. Across three physicists and 75 separate sessions, the average time required to perform the daily adaptive workflow was 16.8 minutes (range:7-29 minutes). 106 subjects are sought as Wilson Score 95%-confidence interval for 25/106=23.6% is [16.5%,32.5%], implying null hypothesis of >=33% toxicity incidence rate can be rejected at a 1-sided p<0.025 significance level if <25/106 subjects report PRO-CTCAE score >3. Power is 0.85 if true incidence rate is 20%. Conclusion(s): The ARTIA-Cervix clinical trial will test the hypothesis that adaptive-enabled, reduced-margin cervical cancer radiotherapy reduces acute gastrointestinal toxicity. The study has multi-institutional IRB approval and will begin accrual in Spring 2022. K Moore acknowledges consulting fees and honoraria from Varian Medical Systems. J Mayadev acknowledges consulting fees from Varian Medical Systems. X Ray acknowledges honoraria from Varian Medical Systems and a research agreement with Varian Medical Systems. Varian Medical Systems is the sponsor of this clinical trial.

Moore Kathleen, N., et al. (2023). "Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer." The New England Journal of Medicine 389(23): 2162-2174.
	Background: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States.; Methods: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes.; Results: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%).; Conclusions: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.). (Copyright © 2023 Massachusetts Medical Society.)

Moore Kathleen, N., et al. (2022). "Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study." Clinical cancer research : an official journal of the American Association for Cancer Research 28(1): 36-44.
	Purpose: This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer.; Patients and Methods: Women with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled between January 2015 and January 2018 in this open-label, four-arm, multicenter, phase II study. Patients received adavosertib (oral capsules, 2 days on/5 days off or 3 days on/4 days off) in six cohorts from 175 mg once daily to 225 mg twice daily combined with gemcitabine, paclitaxel, carboplatin, or pegylated liposomal doxorubicin. The primary outcome measurement was overall response rate.; Results: Three percent of patients (3/94) had confirmed complete response and 29% (27/94) had confirmed partial response. The response rate was highest with carboplatin plus weekly adavosertib, at 66.7%, with 100% disease control rate, and median progression-free survival of 12.0 months. The longest median duration of response was in the paclitaxel cohort (12.0 months). The most common grade ≥3 adverse events across all cohorts were neutropenia [45/94 (47.9%) patients], anemia [31/94 (33.0%)], thrombocytopenia [30/94 (31.9%)], and diarrhea and vomiting [10/94 (10.6%) each].; Conclusions: Adavosertib showed preliminary efficacy when combined with chemotherapy. The most promising treatment combination was adavosertib 225 mg twice daily on days 1-3, 8-10, and 15-17 plus carboplatin every 21 days. However, hematologic toxicity was more frequent than would be expected for carboplatin monotherapy, and the combination requires further study to optimize the dose, schedule, and supportive medications. (©2021 American Association for Cancer Research.)

Moore, K. H., et al. (2022). "Efficacy and patient acceptability of the continence dish." International Urogynecology Journal 33(5): 1199-1205.
	Introduction and hypothesis: The continence dish has been a treatment option since 2002 for women with stress urinary incontinence (SUI) who decline surgery, but few quantitative objective efficacy data are published. We aimed to determine the efficacy and acceptability of this device for pure SUI or mixed incontinence (MUI). Method(s): Prospective interventional cohort study of 100 women with SUI or stress-predominant MUI who were interested to use the device; International Consultation on Incontinence Questionnaire (ICIQ) was primary outcome measure; 24-h pad test and Incontinence Impact Questionnaire (IIQ) were secondary outcomes. Acceptability was determined by device retention for 4 weeks, adverse events and ability to self-insert the device. Result(s): Of 100 suitable women, 9 were not actually fitted, and 27 did not complete (acceptability: 64/100). The rate of adverse events was 7.7%, with 62.5% of users able to self-insert the device: 22 (34%) had pure SUI; 66% had MUI. In SUI, 68% were 'dry' on ICIQ median value 4.0 (IQR 2.5-8.5); 88% were dry on 24-h pad test (median 0.0, IQR 0.0-8.5). The "dry rate" was lower in MUI: 36% for ICIQ (median 9.0, IQR 5.0-15.0) and 62% for 24-h pad test (median 6.2, IQR 0.95-19.7). A "good" response on IIQ occurred in 88% of SUI and 69% of MUI. Conclusion(s): These new data showing strong objective benefits of the continence dish should be further validated by randomized trials, but this information should be made available to women seeking treatment options for SUI/MUI (particularly in view of concerns regarding mesh mid-urethral slings).Copyright © 2021, Crown.

Moore, K. N., et al. (2023). "Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximab soravtansine vs. investigator's choice of chemotherapy in platinum-resistant, advanced highgrade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression." Journal of Clinical Oncology 41(17 Supplement).
	Background: Mirvetuximab soravtansine (MIRV), an antibody drug conjugate targeting FRa, demonstrated clinically meaningful antitumor activity in a single arm trial reported previously (Matulonis, JCO 2023). MIRASOL is a randomized phase 3 trial to confirm the efficacy of MIRV vs standard-of-care chemotherapy in patients (pts) with PROC. Method(s): 453 PROC pts with high FRa expression (Roche FOLR1 Assay) with 1-3 priors were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was progressionfree survival (PFS) by investigator (INV) with key secondary endpoints ORR, overall survival (OS), and patient-reported outcomes in hierarchical order; other endpoints included safety and tolerability. Blinded independent central review (BICR) for PFS and ORR were sensitivity analyses. Result(s): With a data cutoff of March 6, 2023, 227 pts were randomized to the MIRV arm; 226 to the IC arm. Median follow-up was 13.1 months. Baseline characteristics were well balanced across arms; 14% of pts had one, 39% two, and 47% three prior lines of therapy; 62% received prior bev; and 55% received prior PARPi therapy. The study met its primary and key secondary endpoints with statistically significant results in PFS (INV), ORR (INV), and OS (Table). In the bev-pretreated subset (n=281), PFS HR was 0.64 (0.492, 0.842) and OS HR was 0.74 (0.535, 1.036); in the bev-naive subset (n=172), PFS HR was 0.66 (0.459, 0.942) and OS HR was 0.51 (0.306, 0.860). The adverse event (AE) profile of MIRV was consistent with prior reports: predominantly low-grade ocular (MIRV vs IC all grade 56% vs 9%; grade 3+ 14% vs 0%) and gastrointestinal events (MIRV vs IC all grade 70% vs 66%; grade 3+ 13% vs 15%). Compared with IC, MIRV was associated with lower rates of grade 3+ treatment-emergent AEs (42% vs 54%), serious AEs (24% vs 33%), and discontinuations due to TEAEs (9% vs 16%). Fourteen percent of pts on the MIRV arm remained on study drug vs 3% on the IC arm. Conclusion(s): MIRV is the first treatment to demonstrate a PFS and OS benefit in PROC compared to IC. The efficacy data, along with the well-characterized safety profile, position MIRV as a new, standard of care for pts with FRa positive PROC.

Moore, K. N., et al. (2023). "Mirvetuximab Soravtansine in FRalpha-Positive, Platinum-Resistant Ovarian Cancer." New England Journal of Medicine 389(23): 2162-2174.
	BACKGROUND Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor alpha (FRalpha), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRalpha tumor expression (>=75% of cells with >=2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. RESULTS A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P=0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). CONCLUSIONS Among participants with platinum-resistant, FRalpha-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.)Copyright © 2023 Massachussetts Medical Society. All rights reserved.

Moore, K. N., et al. (2022). "197TiP First-in-human (FIH) phase I/II study of ubamatamab, a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer (OC)." Immuno-Oncology and Technology 16(Supplement 1): 100309.
	Background: Mucin-16 is a cell surface glycoprotein that is overexpressed in epithelial OC. Ubamatamab (REGN4018) is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell-mediated cytotoxicity by facilitating contact between cancer cells and T cells. Cemiplimab is an anti-programmed cell death-1 monoclonal antibody. The phase 1 study in patients with recurrent OC found ubamatamab monotherapy had an acceptable safety profile, durable clinical activity across a range of doses (as measured by RECIST and cancer antigen 125 [CA-125] response rates), and linear pharmacokinetics up to 800 mg weekly intravenous (IV)1. These clinical data support further evaluation of a once every 3-week (Q3W) regimen of ubamatamab alone and in combination with cemiplimab. Trial Design: In phase 2, up to 150 patients with advanced platinum-resistant OC and elevated serum CA-125 will be randomised to three IV arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 patients. Any arm with >=3 objective responses will be expanded to 50 patients. In this dose expansion phase the primary endpoint will be the objective response rate for each arm as defined by RECIST 1.1 criteria. Secondary endpoints include evaluation of duration of response and progression-free survival as well as further evaluation of safety and pharmacokinetics. Exploratory endpoints include evaluation of baseline tumour MUC16 immunohistochemistry expression and other biomarkers as predictors of response. The impact of ubamatamab on quality of life and physical functioning will also be assessed. Final data are pending for this TiP. Reference 1: Annals of Oncology (2022) 33 (suppl_7): S235-S282. 10.1016/annonc/annonc1054. Clinical trial identification: NCT03564340. Editorial acknowledgement: Medical writing support was provided by Rachel McGrandle, BSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc. Funding(s): Regeneron Pharmaceuticals, Inc. Disclosure: K.N. Moore: Financial Interests, Personal, Advisory Role: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Caris, Elevar, Eisai, Genentech/Roche, GSK/Tesaro, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Mereo, Myriad, Mersana, Novocure, Novartis, Tarveda, Verastem and VBL Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Regeneron, Novocure, Genentech/Roche, AbbVie, GSK/Tesaro, Immunogen, PTC Therapeutics, Merck, Lilly, Mereo, Artios and Daichii. S. Bouberhan: Financial Interests, Personal, Advisory Role: ImmunoGen. E. Hamilton: Financial Interests, Institutional, Research Grant: Regeneron, AbbVie, Acerta Pharma, ADC Therapeutics, Akesobio Australia, Amgen, Aravive, ArQule, Arvinas, AstraZeneca, AtlasMedX, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Dana Farber Cancer Inst, Daiichi Sankyo, Deciphera, eFFE; Financial Interests, Institutional, Advisory Role: Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roc. J. Liu: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Eisai, EpsilaBio, Genentech/Roche, GlaxoSmithKline and Regeneron Pharmaceuticals, Inc.; Financial Interests, Institutional, Research Grant: 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, Vigeo Therapeutics and Zentalis. R.E. O'Cearbhaill: Financial Inte ests, Personal, Other, Personal fees: Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, Immunogen, Curio and MJH; Financial Interests, Personal, Other, Travel support for meeting: Hitech Health; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Role: PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca); Non-Financial Interests, Personal, Advisory Role: Carina Biotech; Financial Interests, Institutional, Research Grant: Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, AbbVie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma and. D. O'Malley: Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), Ambry, Myriad Genetics, Tarveda, Novartis, Rubis, Elevar, Takeda, Toray, INXMED, Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics and Celsion Corp; Financial Interests, Personal, Research Grant: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., Cerulean Pharma, Bristol Myers Squibb Co., Serono Inc., TRACON Pharmaceuticals, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health C. S. Yoo: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Peterman: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. P. Goncalves: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. T. Schmidt: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Zhu: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Uldrick: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. E.A. Miller: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Moore, K. N., et al. (2023). "41P Phase I analysis of ubamatamab (MUC16xCD3 bispecific antibody) in patients with recurrent ovarian cancer." ESMO Open 8(1 Supplement 1): 100821.
	Background: Ubamatamab (REGN4018) is a mucin 16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell-mediated cytotoxicity by binding MUC16-expressing ovarian cancer (OC) cells and CD3+ T cells. We present safety, efficacy and pharmacokinetic (PK) modelling from a first-in-human study of ubamatamab (NCT03564340). Method(s): Patients (pts) with recurrent platinum-experienced OC received ubamatamab 0.3-800 mg intravenously weekly (QW) after initial step-up dosing. Primary endpoints were safety and PK. Secondary and exploratory endpoints included objective response rate per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, disease control rate (a response or stable disease) and cancer antigen 125 (CA-125) response per Gynecological Cancer InterGroup criteria. Result(s): 78 pts received ubamatamab 0.3-800 mg without reaching maximal tolerated dose. Median number of prior therapies was 4.5 (range 1-17). Median ubamatamab exposure was 12 (range 1-117) weeks. Commonest treatment-emergent adverse events (TEAEs) were cytokine release syndrome (73.1%, all Grade 1/2) and pain (87.2%), primarily occurring in Weeks 1-2 of step-up dosing. Commonest Grade >=3 TEAEs were anemia (24.4%) and abdominal pain (20.5%). Objective responses were observed between 20-800 mg. In 42 pts receiving >=1 full dose of >=20 mg, ORR was 14.3% (95% CI, 5.4-28.5), disease control rate was 57.1% (41-72.3), and median duration of response was 12.2 months. 23.8% of pts (12.1-39.5%) had a CA-125 response. Serum ubamatamab concentrations increased dose proportionally. No apparent dose-response relationship was observed from 20-800 mg for safety or efficacy. PK modelling supported the selection of 250 and 800 mg every-3-weeks (Q3W) regimens for Phase 2, as both regimens had a maximum concentration (Cmax) below the Cmax of 800 mg QW, and trough concentration (Cmin) above that of the minimal effective dose (20 mg QW). Conclusion(s): Ubamatamab resulted in an acceptable safety profile and durable responses in a heavily pretreated OC population across a wide dose range. A randomised Phase 2 expansion trial with initial step-up dosing followed by Q3W dosing has been initiated. Clinical trial identification: NCT03564340. Editorial acknowledgement: Editorial support was provided by Rachel McGrandle of Prime Medica, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc. Funding(s): Regeneron Pharmaceuticals, Inc. Disclosure: K.N. Moore: Financial Interests, Personal, Advisory Role: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Caris, Elevar, Eisai, Genentech/Roche, GSK/Tesaro, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Mereo, Myriad, Mersana, Novocure, Novartis, Tarveda, Verastem and VBL Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Regeneron, Novocure, Genentech/Roche, AbbVie, GSK/Tesaro, Immunogen, PTC Therapeutics, Merck, Lilly, Mereo, Artios and Daiichi. D. O'Malley: Financial Interests, Personal, Research Grant: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., Cerulean Pharma, Bristol-Myers Squibb Co., Serono Inc., TRACON Pharmaceuticals, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health C; Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/Johnson & Johnson, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Iovance, Eisai, Agenus, SeaGen, Mersana, Clovis and SDP Oncology (BBI), Ambry, Myriad Genetics, Tarveda, Novartis, Rubis, Elevar, Takeda, Toray, INXMED, Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics and Celsion Corp. E. Hamilton: Financial Interests, Institutional, Research Grant: Regeneron, AbbVie, Acerta Pharma, ADC Therapeutics, AKESOBIO stralia, Amgen, Aravive, ArQule, Arvinas, AstraZeneca, AtlasMedX, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Dana Farber Cancer Inst, Daiichi Sankyo, Deciphera, eFFECTOR Therap; Financial Interests, Institutional, Advisory Role: Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roc. R.E. O'Cearbhaill: Financial Interests, Personal, Invited Speaker, Personal fees: Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, Immunogen, R-Pharm, Onclive, Curio and MJH; Financial Interests, Personal, Other, Travel support for meeting: Hitech Health; Non-Financial Interests, Personal, Advisory Role, Steering committee: PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies; Non-Financial Interests, Personal, Advisory Role: Carina Biotech; Financial Interests, Institutional, Research Grant: Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, AbbVie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma and; Financial Interests, Personal, Other, NRG representative: ComboMATCH study. O. Yeku: Financial Interests, Personal, Advisory Role: Celldex, GIMV NV, TigaTx and hC Bioscience. S. Bouberhan: Financial Interests, Personal, Advisory Role: ImmunoGen. M. Peterman: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. P. Goncalves: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. T. Schmidt: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M. Zhu: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Rowlands: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. T. Uldrick: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. E.A. Miller: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. J. Liu: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Eisai, EpsilaBio, Genentech/Roche, GlaxoSmithKline and Regeneron Pharmaceuticals, Inc.; Financial Interests, Institutional, Research Grant: 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, Vigeo Therapeutics and Zentalis. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Moore, K. N., et al. (2022). "Analyses of patient-reported outcomes (PROs) with mirvetuximab soravtansine (MIRV) versus standard chemotherapy in the randomized phase III FORWARD I study in ovarian cancer (GOG 3011)." Annals of Oncology 33(Supplement 7): S790-S791.
	Background: MIRV, a first-in-class antibody-drug conjugate targeting folate receptor alpha (FRalpha), is currently under investigation for the treatment of patients (pts) with platinum-resistant ovarian cancer in the phase 3 clinical trial MIRASOL. Analyses of PROs collected as part of the phase 3 FORWARD I trial informed the collection of PRO data for MIRASOL. Method(s): PROs from the EORTC-QLQ-OV28 (OV28), EORTC-QLQ-C30 (C30), and FOSI modules were collected during the FORWARD I trial, and preplanned analyses were conducted on data from the intent-to-treat (ITT) and FRalpha-high populations. To inform future studies, additional exploratory analyses were conducted. Result(s): In the ITT population, the primary analysis of OV28 gastrointestinal (GI) symptoms demonstrated a statistically significant improvement of >=15 points at week 8/9 in pts treated with MIRV vs chemotherapy (CTX) (31.7% vs 14.0%; P = 0.0162). The likelihood of GI symptom deterioration was 70% lower with MIRV compared with CTX (P = 0.0007). Analyses of C30 demonstrated a statistically significant benefit in physical functioning for MIRV over CTX (P= 0.0369). There were improvements in the chemotherapy side effects, sexuality, hair loss, pain severity, body image, and a general improvement in ovarian cancer-specific symptoms on the FOSI, for MIRV vs CTX. In the FRalpha-high population, analysis of OV28 also demonstrated improvement in GI symptoms for MIRV vs CTX, although this did not achieve statistical significance (27.3% vs 13.3%; P = 0.1426). The likelihood of GI symptom deterioration was 80% lower with MIRV compared with CTX (P = 0.0007). Median time to symptom worsening on the OV28 abdominal/GI scale was longer for MIRV vs CTX (4.0 mo vs 2.1 mo; P = 0.0229). Improvements were seen in chemotherapy side effects, sexuality, hair loss, and body image with MIRV vs CTX. Conclusion(s): Analyses of PROs from FORWARD I support MIRV in favor of CTX in pts with ovarian cancer, including those with high FRalpha expression, with improvements across a number of QoL measures. With the addition of an anchor assessment, we look to confirm these findings in MIRASOL and to further understand the degree of change in PROs that is meaningful to patients. Clinical trial identification: NCT02631876. Legal entity responsible for the study: ImmunoGen. Funding(s): ImmunoGen. Disclosure: K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Eisai, Emd Serono, Gsk/Tesaro, Genentech/Roche, Hengrui, ImmunoGen, IMab, Mereo, Myriad, Caris, Mersana, Novartis, Novocure, OncXerna, OncoNova, Tarveda, VBL Therapeutics; Financial Interests, Personal, Full or part-time Employment: GOG Partners Associate Director; Financial Interests, Institutional, Full or part-time Employment: NRG Ovarian Cancer Chair; Financial Interests, Personal, Royalties: UP to Date; Financial Interests, Institutional, Invited Speaker, international CO-PI, local site PI: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Immunogen, GSK/Tesaro, Lilly, PTC Therapeutics, Daiichi Sankyo, Regeneron, Artios, Bolt, Verastem; Non-Financial Interests, Invited Speaker: GOG. A.M. Oza: Financial Interests, Personal, Advisory Board, 2019: ImmunoGen; Financial Interests, Institutional, Other, Research investigator on trials: ImmunoGen. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de Espana, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann -La Roche LTD, Regeneron Pharmaceuticals, ImmunoGen Inc, Merck, Sharp & Dohme de Espana SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Johnson & Johnson, Astrazeneca&MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline; Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: Astrazeneca; Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Invited Speaker, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financ l Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: roche; Non-Financial Interests, Member, Board of Directors: GCIG. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca; Non-Financial Interests, Advisory Role: Epsilogen; Non-Financial Interests, Other, Member of membership committee: ESGO; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. C. Murphy: Financial Interests, Personal, Advisory Board: Daiichi Sanko; Financial Interests, Personal, Invited Speaker: Daiichi Sanko, Janssen. J. Konner: Financial Interests, Personal, Advisory Board: AstraZeneca, clovis. P. Lim: Financial Interests, Institutional, Other, Investigator: Immunogen. M. Prasad-Hayes: Financial Interests, Institutional, Other, Investigator: Immunogen. B.J. Monk: Financial Interests, Personal, Other, Consulting: Abbvie, Amgen, Aravive, Astrazeneca, Clovis, GOG Foundation, Gradalis, ImmunoGen, Laekna Healthcare, Merck, Mersana, Myriad, NuCana, OncoMed, OncoQuest, Pfizer, Roche/Genentech, Tesaro/GSK; Financial Interests, Institutional, Other, Investigator: Immunogen. J. Wang: Financial Interests, Institutional, Other, Investigator: Immunogen. M.J. Birrer: Financial Interests, Personal, Advisory Board: AstraZeneca, Mersana. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019) inancial Interests, Institutional, Research Grant, Contracted Research ( via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020).Copyright © 2022 European Society for Medical Oncology

Moore, K. R., et al. (2022). "Bacterial Vaginosis and Prospective Ultrasound Measures of Uterine Fibroid Incidence and Growth." Epidemiology 33(3): 415-421.
	Background: Uterine fibroids often cause intolerable symptoms leading to invasive treatments, most commonly hysterectomy. Reproductive tract infections are hypothesized to influence uterine fibroid development, but few studies exist, especially for the highly prevalent condition bacterial vaginosis (BV). Both fibroids and BV have documented racial-ethnic disparities, with higher burden in Blacks. Method(s): With prospective data from a community-based study (four standardized ultrasound examinations over 5 years) in young Black women, we examined baseline BV associations with fibroid incidence and growth. We computed adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incidence comparing BV and no BV (Nugent score >=7 vs. <7) using Cox proportional hazards models among 1027 women fibroid-free at baseline. Fibroid growth associations were based on linear mixed models estimating volume change between ultrasounds indexed to 18 months. We then expressed BV association as estimated percent difference in growth per 18 months, comparing exposed and unexposed. Result(s): There were n = 247 incident fibroids and 1181 growth measures; average fibroid growth per 18 months was a 78% (95% CI: 69 to 87) increase in volume. BV prevalence was 51% and not associated with fibroid incidence (aHR: 1.0, 95% CI: 0.80 to 1.4) or growth (estimated % difference in growth, -3% (95% CI: -12 to 6). Conclusion(s): In this first study (to our knowledge) of ultrasound-monitored fibroid development and Nugent-assessed BV, we found no evidence to support the hypothesis that BV increased risk of fibroid incidence or growth or BV's role in the high burden of fibroids in Black women.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Moore, S., et al. (2019). "The PRogram In Support of Moms (PRISM): study protocol for a cluster randomized controlled trial of two active interventions addressing perinatal depression in obstetric settings." BMC Pregnancy and Childbirth 19(1): 256.
	Background: Perinatal depression, the most common pregnancy complication, is associated with negative maternal-offspring outcomes. Despite existence of effective treatments, it is under-recognized and under-treated. Professional organizations recommend universal screening, yet multi-level barriers exist to ensuring effective diagnosis, treatment, and follow-up. Integrating mental health and obstetric care holds significant promise for addressing perinatal depression. The overall study goal is to compare the effectiveness of two active interventions: (1) the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms, a state-wide, population-based program, and (2) the PRogram In Support of Moms (PRISM) which includes MCPAP for Moms plus a proactive, multifaceted, practice-level intervention with intensive implementation support.; Methods: This study is conducted in two phases: (1) a run-in phase which has been completed and involved practice and patient participant recruitment to demonstrate feasibility for the second phase, and (2) a cluster randomized controlled trial (RCT), which is ongoing, and will compare two active interventions 1:1 with ten Ob/Gyn practices as the unit of randomization. In phase 1, rates of depressive symptoms and other demographic and clinical features among patients were examined to inform practice randomization. Patient participants to be recruited in phase 2 will be followed longitudinally until 13 months postpartum; they will have 3-5 total study visits depending on whether their initial recruitment and interview was at 4-24 or 32-40 weeks gestation, or 1-3 months postpartum. Sampling throughout pregnancy and postpartum will ensure participants with different depressive symptom onset times. Differences in depression symptomatology and treatment participation will be compared between patient participants by intervention arm.; Discussion: This manuscript describes the full two-phase study protocol. The study design is innovative because it combines effectiveness with implementation research designs and integrates critical components of participatory action research. Our approach assesses the feasibility, acceptance, efficacy, and sustainability of integrating a stepped-care approach to perinatal depression care into ambulatory obstetric settings; an approach that is flexible and can be tailored and adapted to fit unique workflows of real-world practices.; Trial Registration: ClinicalTrials.gov Identifier: NCT02760004, registered prospectively on May 3, 2016.

Moradi, F., et al. (2022). "The efficacy of Trans-cutaneous Electrical Nerve Stimulation (TENS) with psychological supportive intervention on pain and maternal -neonatal outcomes of childbirth in pregnant women referring to Maternity ward." Iranian Journal of Obstetrics, Gynecology and Infertility 25(6): 61-70.
	Introduction: The factors which lead to a reduction in pain and length of labor with minimal intervention have always been of interest to researchers. The present study was performed aimed to compare the effect of TENS with psychological supportive intervention on labor pain and maternal and neonatal outcomes in pregnant women referring to the maternity ward. Method(s): This clinical trial study was performed in 2021 on 90 pregnant women admitted to the delivery block of Payambar Azam hospital of Kerman. The subjects were randomly divided into three groups of TENS (n=30), psychological supportive intervention (n=30) and control (n=30). In the active labor phase, TENS was applied for the TENS group, the psychological supportive intervention was performed in the counseling group, and routine care was performed for the control group. Scores of pain during the active phase of labor (4 cm and 10 cm dilatation) and maternal and neonatal outcomes were compared in the three groups. Data were analyzed by SPSS statistical software (version 21) and Fisher's exact and variance analysis tests. P< 0.05 was considered statistically significant. Result(s): There was no significant difference between the three groups in the scores of labor pain in 4 cm dilatation, maternal complications, Apgar scores 1 and 5 minutes, and type of delivery (p> 0.05). However, the score of pain in 10 cm dilatation in the TENS group and counseling group similarly was significantly reduced compared to the control group. The duration of the first stage of active phase labor was not significantly different between the three groups (p> 0.05), but the difference between the duration of the second stage of the active phase and the total duration of the active phase was significant between the three groups (p >0.05). Conclusion(s): Both methods of psychological supportive counseling and transcutaneous electrical nerve stimulation (TENS) are equally effective in reducing labor pain and length of labor; considering the safety of both methods, it is recommended to use these two methods to facilitate the birth process.Copyright © 2022, Mashhad University of Medical Sciences. All rights reserved.

Moradi, F., et al. (2021). "The effectiveness of group counseling based on acceptance and commitment therapy on body image and self-esteem in patients with polycystic ovary syndrome: an RCT." International Journal of Reproductive Biomedicine 19(5 SUPPL 1): 125.
	Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive age women which is known with irregular menstruation, hirsutism, alopecia, obesity, infertility, and acne. These symptoms cause a negative effect on the satisfaction of body image, self‐esteem, and quality of life in these patients. Recent studies emphasize the need to consider the psychological problems in these women and also the need for appropriate interventions. Objective: The aim of this study was to determine the effectiveness of group counseling based on acceptance and commitment therapy (ACT) on body image and self‐esteem in patients with PCOS. Materials and Methods: This randomized controlled trial was performed on 52 women with PCOS who met the inclusion criteria (aged 18‐45 yr, Iranian resident in Yazd, and diagnosed with PCOS according to Rotterdam criteria and endocrinologist diagnosis). Then, these women were randomly allocated to intervention and control groups (n = 26/each) using the table of random numbers. Group counseling based on the acceptance and commitment therapy was held in eight sessions of 90 min once a week for the intervention group. The demographic questionnaire, Littleton development of the body image concern inventory and Rosenberg self‐esteem scale were completed in both groups before, immediately after, and one month after the intervention. Data were analyzed using the SPSS software (version 16.0). Normality of data was analyzed using the Kolmogorov‐Smirnov test. Due to the normal distribution, parametric statistical tests (Independent t test and repeated measure test) were used to analyze the data. p < 0.05 was considered as significant. Results: The results showed that there was no significant difference in the mean of body image concern scores between the intervention and control groups before intervention, but this difference was significant between the studied groups in two stages of after the intervention and follow‐up. In an intra‐group comparison of intervention group participants, the results indicated a significant decrease (p = 0.001) in the body image concern scores in all three stages of intervention. The mean score of self‐esteem before the intervention was not significantly different between the groups. But after the intervention, the mean changes significantly differed between the two groups, and one month after the intervention, there was no significant difference between the two groups. In an intra‐group comparison of intervention group, the mean scores of self‐esteem in three stages of the intervention was significantly (p ≤ 0.001) changed . Conclusion: Based on the findings of this study, use of cognitive‐behavioral therapies in health care centers is recommended as a complementary method.

Moradi, F., et al. (2022). "The Effects of a Special Food (Fried Eggs With Grape Molasses) on Threatened Miscarriage in Combination With Conventional Therapies: a Randomized Clinical Trial." International Journal of Women's Health and Reproduction Sciences 10(3): 141‐147.
	Objectives: Threatened miscarriage is a common disorder in early pregnancy and is seen in 20% of pregnant women. Currently, there is no effective therapeutic solution for this condition. This study aimed to determine the effects of a special food (fried egg with grape molasses) on threatened miscarriage in combination with conventional therapies. Materials and Methods: This randomized controlled clinical trial was conducted on 93 pregnant women with mild or moderate vaginal bleeding up to 16 weeks of gestation in two groups. The control group (n = 47) used progesterone 400 mg suppository daily with abstinence from sexual intercourse and physical activity. The intervention group (n = 46) consumed fried eggs with grape molasses and the routine treatment like the control group. The treatment was considered successful if the pregnancy continued up to 20 weeks. Finally, the risk of abortion (miscarriage rate) and the duration of vaginal bleeding were compared between two groups. Results: The risk of abortion in the control group was about 26% (12 of 45 pregnancies), while in the intervention group, it was 15% (7 of 45 pregnancies). This result was not statistically significant between the two groups (Risk ratio: 0.69, 95% CI: 0.37‐1.30, P = 0.197). Additionally, no significant difference was detected regarding the duration of vaginal bleeding between the intervention and control groups (P = 0.699). Conclusions: There is no significant statistical relationship between the consumption of “fried eggs with grape molasses” and reduction of abortion risk.

Moradi Luke, A., et al. (2022). "Hypofractionated radiation leads to more rapid bleeding cessation in women with vaginal bleeding secondary to gynecologic malignancy." Radiation oncology (London, England) 17(1): 34.
	Background: Vaginal bleeding (VB) is common in women with gynecologic (GYN) malignancies. Radiation therapy (RT) is used for the definitive treatment of GYN cancers and palliation of bleeding. The historical dogma is that high dose-per-fraction radiation leads to more rapid bleeding cessation, yet there is scant data supporting this claim. We sought to examine the effect of RT fraction size on VB via retrospective analysis of patients receiving hypofractionated radiation (HFRT) compared to conventionally fractionated radiation (CFRT) for control of bleeding secondary to GYN malignancies.; Methods: We identified patients receiving external beam RT for continuous VB from GYN malignancy treated in our department from 2012 to 2020. RT was classified as HFRT (> 2.0 Gy/fx) or CFRT (1.8-2.0 Gy/fx). Demographic information, disease characteristics, and treatment details were collected. The primary endpoint was days from RT initiation until bleeding resolution. Characteristics between groups were compared via Fisher's exact test. Time to bleeding cessation was assessed via Kaplan-Meier and log-rank test. Univariable and multivariable Cox-proportional hazards were used to identify factors associated with bleeding cessation.; Results: We identified 43 patients meeting inclusion criteria with 26 and 17 patients receiving CFRT and HFRT, respectively. Comparison of baseline characteristics revealed patients receiving HFRT were older (p = 0.001), more likely to be post-menopausal (p = 0.002), and less likely to receive concurrent chemotherapy (p = 0.004). Time to bleeding cessation was significantly shorter for patients receiving HFRT (log-rank p < 0.001) with median time to bleeding cessation of 5 days (HFRT) versus 16 days (CFRT). Stratification by dose-per-fraction revealed a dose-response effect with more rapid bleeding cessation with increased dose-per-fraction. While HFRT, age, recurrent disease, prior pelvic RT, and prior systemic therapy were associated with time to bleeding cessation on univariable analysis, HFRT was the only factor significantly associated with time to bleeding cessation in the final multivariable model (HR 3.26, p = 0.008).; Conclusions: Patients with continuous VB from GYN tumors receiving HFRT experienced more rapid bleeding cessation than those receiving CFRT. For patients with severe VB, initiation of HFRT to control malignancy related bleeding quickly may be warranted. (© 2022. The Author(s).)

Moragrega, I. and J. L. Rios (2022). "Medicinal Plants in the Treatment of DepressionII: Evidence from Clinical Trials." Planta Medica 88(12): 1092-1110.
	Depression is a syndrome characterized by deep sadness and the inhibition of psychic functions, sometimes accompanied by neurovegetative disorders, with symptoms of anxiety almost always present. The disease produces alterations in a variety of neural networks and neurotransmission systems, along with a dysfunction of the hypothalamic-pituitary-adrenal axis, which leads to concomitant alterations in the immunological response. Generally, there is a parallel increase in proinflammatory mediators as well as oxidative and nitrosative damage caused by a reduction of antioxidant defenses. In a previous review, we compiled and examined studies of medicinal plants that had been evaluated in preclinical assays, including existing data on 155 species studied and reported as antidepressants or as sources of active principles for treating this condition. This review will thus limit its focus to the 95 clinical trials found in PubMed among the 670 articles on antidepressant-like medicinal plants. To this end, we have reviewed the publications cited in the Cochrane Database of Systematic Reviews, PubMed, and the Science Citation Index from 2000 to 2020. Our review emphasizes those species that have demonstrated the greatest pharmacological potential when studied for their antidepressant properties in humans through clinical trials. Saffron, turmeric, St. John s wort, ginkgo, kava, and golden root are the most relevant plants that have provided important evidence for the treatment of depression in clinical trials.Copyright © 2022 Georg Thieme Verlag. All rights reserved.

Moran, L., et al. (2023). "Suicidal ideation and depressive symptoms in an urban post-partum maternity setting: a retrospective cohort study." Irish journal of psychological medicine 40(4): 566-570.
	Background: Fifteen percent of women worldwide experience depression in the perinatal period. Suicide is now one of the leading causes of maternal mortality in developed countries. Internationally, many healthcare systems screen post-natal women for depressive symptoms and suicidal ideation to facilitate early assessment and intervention. To our knowledge, no Irish data exists on the prevalence of suicidal ideation in this cohort.; Aims: To evaluate the prevalence of suicidal ideation and depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) in post-natal women attending a large Dublin maternity hospital.; Methods: A retrospective cohort study was conducted. Women were randomly selected by delivery date over a 6 month period. Demographic and medical information was collected from their booking visit and discharge summary data. EPDS results at discharge post-partum were examined.; Results: Data was collected on 643 women. Post-partum, 19 women (3.4%) had experienced suicidal ideation in the previous 7 days. Just over half of these women also had high EPDS scores (>12). Overall, 29 women (5.2%) screened positive for depression (EPDS score > 12).; Conclusions: The rate of suicidal ideation is in line with the published international data and emphasises the need for all clinicians to inquire about such thoughts. Training of midwifery and obstetric staff is required. Maternity units should have a policy on the management of suicidal ideation and risk. The prevalence of depressive symptoms post-partum was comparatively low in our study. This could suggest that antenatal screening and early intervention, which are integral parts of the perinatal mental health service, are effective. However, due to limitations of the study, it could also reflect an under-representation of depressive symptom burden in this cohort.

Moran, P., et al. (2023). "Is detrusor underactivity associated with voiding dysfunction after single incision sling surgery?" Minerva urology and nephrology 75(5): 642-648.
	BACKGROUND: Some women experience voiding dysfunction after stress urinary incontinence (SUI) surgery. We explore if detrusor underactivity (DU) found in urodynamic study (UDS) prior to SUI surgery using an adjustable single incision sling (SIS) may be related to voiding dysfunction after surgery. METHOD(S): This is a prospective, diagnostic, transversal, single center study comparing voiding dysfunction after SUI surgery with a SIS (Altis; Coloplast, Humlebaek, Denmark) between women with DU (cases) or normal detrusor (controls). Inclusion criterium was women >=18 years with SUI/mixed UI (stress predominant) operated between June 2013 and December 2020. Exclusion criteria were: women without UDS prior to surgery or without voiding phase in the P/Q, previous incontinence surgery, POP stage >=2, neurogenic conditions, other pelvic floor surgery. Urinary symptoms were assessed using structured questions evaluating storage/voiding symptoms. Patients were divided into two groups according to projected Isovolumetric Pressure Index (PIP1) with 30-75 cmH2O indicating normal contractility. RESULT(S): A total of 139 women were included, 29 (20.9%) in DU group and 110 (79.1%) in control group. Control and DU groups have shown similar objective (75.5% vs. 71.4% P=0.66) and subjective (85.4% vs. 96.1% P=0.22) success rates, respectively, without statistical differences. Voiding symptoms increased after surgery in both groups (+20.7% DU group vs. +8.1% normal group, P=0.29). More voiding symptoms (persistent/de novo) were found in DU group vs. normal group, but without statistically significant differences. CONCLUSION(S): According to our results, the presence of DU previous to SUI surgery with a SIS (Altis, Coloplast) has no impact on objective and subjective success rates. On the other hand, patients with preoperative DU showed higher proportion of voiding dysfunction but no statistical difference.Copyright © 2023 EDIZIONI MINERVA MEDICA.

Morand Grégoire, B., et al. (2022). "Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?" International Journal of Molecular Sciences 23(15).
	The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.

Morán-Sánchez, I., et al. (2021). "Is dispositional optimism associated with endometriomas and deep infiltrating endometriosis?" Journal of Psychosomatic Obstetrics and Gynaecology 42(1): 50-56.
	INTRODUCTION: Endometriosis is a chronic painful condition characterized by high prognostic uncertainty, as well as the threat of infertility and emotional symptoms that may affect many aspects of women, including psychological characteristics like dispositional optimism. Considering the impact of endometriosis on psychological health and the paucity of papers on this topic, the aim of this study is to explore optimism and associated factors in endometriosis. METHODS: A case-control study was performed on a group of 95 women with endometriosis and 156 controls. All participants completed the Life Orientation Test-Revised (LOT-R), a self-administered tool for assessing dispositional optimism. Pain severity, medication, gynecological and socio-demographic information was also collected. RESULTS: Low optimism was observed for women with endometriosis compared to controls even after covariate adjustment (LOT-R global scores: 14.5 vs. 15.9 points, p = .045). CONCLUSIONS: This study provides the first evidence that a personality dimension with many prognostic implications may be altered in women with endometriosis. Our findings highlight the importance of a broader understanding of this condition, treating this disorder from a biopsychosocial perspective and suggests the need for non-medical attention within a multidisciplinary team.

Moravek Molly, B., et al. (2023). "Impact of a single-session psychosocial counseling intervention for women with vulvodynia." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 160(1): 202-208.
	Objective: To evaluate the impact of a single session of psychosocial counseling on patients with vulvodynia.; Methods: Patients diagnosed with vulvodynia at a vulvovaginal specialty clinic were randomly assigned to receive either a one-on-one 30- to 45-min psychosocial counseling session with a psychosexual counselor plus written educational materials (intervention group) or written materials alone (control group). They completed a survey before and 6 weeks after randomization that included demographic information and validated measures of sexual function and illness perception.; Results: Thirty-one of 38 (81.6%) women approached chose to participate; 26 of the 31 (83.9%) completed the 6-week follow-up survey. Only the intervention group showed improvement in knowledge about vulvovaginal and sexual health, as well as in most measures of improvement in illness perception, as measured by the Brief Illness Perception Questionnaire (P < 0.05). When compared directly with those in the control group, patients in the intervention group reported increased understanding of their vulvar symptoms (P < 0.005) and lessened emotional impact of these symptoms (P = 0.035).; Conclusion: Patients receiving one session of the one-on-one psychosocial counseling intervention reported improved understanding and lessened emotional impact of their vulvar symptoms, compared with the control group. This study suggests that improvement may occur following minimal intervention and supports the need for further study. (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Mørch, N. F., et al. (2022). "Bone mass density in lean and overweight women with polycystic ovary syndrome." Scandinavian journal of clinical and laboratory investigation 82(3): 210-217.
	INTRODUCTION: Polycystic ovary syndrome is a condition characterized by hormonal and metabolic disturbances that may affect bone health. The purpose of this study was to investigate the effect of polycystic ovary syndrome on bone mineral density and to examine which clinical characteristics of the syndrome could influence bone mineral density. MATERIALS AND METHODS: We examined 183 premenopausal women: 158 women with polycystic ovary syndrome and 25 healthy age- and body mass index matched controls. Bone mineral density and body composition were investigated by whole-body dual energy X-ray absorption. Total and free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, estradiol, fasting insulin and glucose, parathyroid hormone, calcium and 25-OH-cholecalciferol were measured. The effect of polycystic ovary syndrome on bone mineral density was analyzed by statistical two-way analysis of variance tests and multiple linear regressions for investigating the connection between bone mineral density and selected clinical parameters. RESULTS: Women with polycystic ovary syndrome had significantly lower bone density in the lumbar vertebrae L1-L4 compared to healthy controls, independently of body mass index. We found that total lean body mass was the most important associating factor for bone mineral density and these were strongly correlated throughout all regression analyzes. We found no connection between lumbar bone density and androgen status, hyperinsulinemia, estradiol or calcium homeostasis. CONCLUSIONS: Premenopausal women with polycystic ovary syndrome have lower bone mineral density in the lumbar vertebrae L1-L4 compared to healthy controls. Total lean body mass and polycystic ovary syndrome are significantly associated to this finding.

Morciano, A., et al. (2022). "Laparoscopic ventral rectopexy plus sacral colpopexy: continuous locked suture for mesh fixation. A randomized clinical trial." Archives of Gynecology and Obstetrics 306(5): 1573-1579.
	Purpose: Laparoscopic ventral rectopexy (LVR) plus sacral colpopexy (LSC) is a high-complexity surgical procedure. The aim of the present study was to evaluate a new approach to rectal-mesh fixation during LVR with continuous locked suture.; Methods: This is a prospective randomized double-blinded clinical trial enrolling 80 patients with severe POP and obstructed defecation syndrome (ODS) from November 2016 to January 2021. Patients underwent a "two-meshes" LSC plus LVR and were randomized, regarding rectal mesh fixation, in Group A (extracorporeal interrupted 0 delayed absorbable sutures) and Group B ("U-shaped" running locked 0 delayed absorbable suture). Our primary endpoints were the operative times (OT); the secondary endpoints were the incidence of anatomical failures, vaginal mesh erosions and surgical complications.; Results: A total of 75 patients completed the study. Baseline characteristics were similar between the groups. Overall OT (156 vs 138 min; p < 0.05; treatment reduction of 11.5%) and LVR mesh fixation time (29 vs 16 min; p < 0.05; treatment reduction of 44%), resulted in significantly lower in Group B. No differences were found in terms of anatomic failure, vaginal mesh erosion or intra- or post-operative complications. PGI-I, FSDS and Wexner questionnaires resulted significantly improved after surgery, without statistical differences between the studied surgical procedures.; Conclusion: Laparoscopic continuous locked 0 absorbable suture for LVR mesh fixation guaranteed a faster and effective alternative to multiple interrupted sutures. The significant OT reduction linked to this technique should be considered even more helpful when performing a highly complex surgery such as LVR.; Clinical Trial Registration: NCT05254860 (13/02/2017). (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Moreira Marcelo de, F., et al. (2022). "A single-blind, randomized, pilot study of a brief mindfulness-based intervention for the endometriosis-related pain management." European journal of pain (London, England) 26(5): 1147-1162.
	Background: Women with endometriosis suffer from frequent symptoms despite multiple treatments in tertiary care. Although there is a need for a biopsychosocial perspective on endometriosis treatment, few conservative treatments have been investigated. We aimed to investigate the effects of a brief Mindfulness-Based Intervention (bMBI) in women with deep endometriosis who remain symptomatic despite undergoing conventional medical treatment.; Methods: A randomized controlled trial was performed with two groups: a standard medical treatment plus bMBI program and only standard medical treatment as a control. A total of 63 eligible participants were randomized to bMBI and control groups. The primary outcome was endometriosis-related pain, and secondary outcomes were quality of life and stress perception post-treatment. Analyses were carried out using multiple regression models.; Results: The results show that bMBI significantly improved pain unpleasantness (Cohen's f 2 = 0.67, NNT = 3.2), pelvic pain (Cohen's f 2 = 0.16, NNT = 5.3) and dyschezia (Cohen's f 2 = 0.23, NNT = 2.9) immediately post-treatment and decreased all endometriosis-related pain (Cohen's f 2 ranging from 0.20 to 0.60 and NNT ranging from 5 to -9) after the follow-up. We found an extensive positive effect of bMBI on the mental health dimension in the two time point measures (Cohen's f 2 = 0.34 and 0.25, NNT = 3.5 and 2.3) and vitality (Cohen's f 2 = 0.22, NNT = 2.1) after the follow-up.; Conclusions: Our study suggests that bMBI is useful for managing endometriosis-related pain and restoring women's psychological well-being.; Significance: Brief Mindfulness-Based Intervention (bMBI) improved endometriosis-related pain and mental health compared to standard medical care. The present findings contribute to the applicability of MBI in visceral pain patients. (© 2022 European Pain Federation - EFIC®.)

Moreira Marcelo de, F., et al. (2023). "Cognitive-affective changes mediate the mindfulness-based intervention effect on endometriosis-related pain and mental health: A path analysis approach." European journal of pain (London, England) 27(10): 1187-1202.
	Background: There is poor knowledge about the therapeutic mechanisms of the conservative interventions for endometriosis. We hypothesized that the effects of a brief mindfulness-based intervention (bMBI) on pelvic pain intensity (PPI), pain unpleasantness (PU) and quality of life mental health (QoL-MH) are mediated by direct and indirect paths of changes in pain catastrophizing (PC), positive affect (PA) and negative affect (NA).; Methods: A secondary analysis of a pilot randomized controlled trial of women with endometriosis, assigned to standard medical treatment (n = 32) and standard medical treatment plus bMBI (n = 31). We tested a series of parallel and serial mediators (PC, PA and NA) of the relationship between bMBI and outcomes (PPI, PU and QoL-MH).; Results: The bMBI group demonstrated improvement in PA (Cohen's f 2 = 0.12 [0.01, 0.36]), decreases in NA (Cohen's f 2 = 0.06 [0.00, 0.24]) and PC (Cohen's f 2 = 0.16 [0.02, 0.42]). The PC reduction mediated the effect of the bMBI on PPI and PU directly; however, the PC effect through PA increase mediated the PU marginally but not PPI changes. bMBI effect on Qol-MH was mediated directly by PA and NA. The PC improved Qol-MH through PA increase and Pain decrease but not via NA.; Conclusions: Our findings showed that bMBI impacts pain through changes in pain-related cognitive-affective factors. bMBI can improve QoL-MH by multiple pathways, including but not limited to pain reduction, highlighting the independent potential of improvement in affect to restore mental health in endometriosis.; Significance: Brief mindfulness-based intervention improves endometriosis pain through pain-related cognitive-affective factors and quality of life mental health via pain and affect changes unrelated to pain. (© 2023 European Pain Federation - EFIC ®.)

Moreira, M. F., et al. (2023). "Mindfulness-Based Intervention Effect on the Psychophysiological Marker of Self-Regulation in Women With Endometriosis-Related Chronic Pain." The journal of pain.
	Endometriosis is a gynecological disease that involves a broad biopsychosocial compromise with the potential to create a negative vicious cycle. Despite the complexity of factors influencing women's improvement, most interventions investigated target just the peripheral nociceptive sources of endometriosis-related pain. An alternative is intervening in self-regulation, which can potentially influence multiple domains of the illness experience. The present study examines the effect of a brief Mindfulness-Based Intervention (bMBI) on attention and autonomic nervous system regulation in women with endometriosis-related pain. Also, explore the interaction between these self-regulation domains and the affective pain dimension. An exploratory analysis of the secondary outcomes of a pilot randomized controlled trial was performed. The vagally-mediated Heart Rate Variability (vmHRV) at rest, cognitive stress, and recovery was employed to measure autonomic regulation. The Flanker and Stroop tasks were used to estimate the attention domains. Results showed that bMBI (n = 26) significantly improved Flanker accuracy and Flanker and Stroop reaction time compared to the control group (n = 28). bMBI significantly increased vmHRV at rest and recovery after cognitive stress. Attention mediated the bMBI effect on affective pain improvement. Results suggest that bMBI improves self-regulation domains with the potential to develop a broad biopsychosocial benefit in the endometriosis context. PERSPECTIVE: This article demonstrates the positive impact of a brief Mindfulness-Based Intervention on attention and parasympathetic regulation in women suffering from endometriosis-related pain. This mindfulness-induced self-regulation improvement can benefit affective pain and potentially multiple psychophysiological processes relevant to endometriosis.

Moreira, R. J., et al. (2022). "Capio TM Slim Suture Device x Tissue Anchoring System has different results in treatment of advanced pelvic organ prolapse? Prospective and Randomized study: Partial Results with 12 months follow-up." European Urology 81(Supplement 1): S1453-S1454.
	Introduction & Objectives: Pelvic organ prolapse (POP) surgeries using mesh, in countries like Brazil, remains as an option for patients with a high risk of recurrence of prolapse and further studies are needed to define its priority and safety for use in patients with advance prolapse. The objective is to compare the effect and safety of POP treatment at an advanced stage using two hysteropexy techniques. Material(s) and Method(s): Prospective, randomized, simple blind study comparing two hysteropexy techniques for POP treatment. Adult women, over 45 years old, with advanced pelvic organ prolapse, stage III or IV of POP-Q, anterior and apical (uterus or dome) were selected. Patients with exclusively posterior prolapse were not included. The sample was randomized to treat 86 patients using two different types of hysteropexy (UpHOLD using a CAPIO TM sling suture device x SPLENTIS using a harpoon anchorage fixation) for follow-up up to 12 months. Objective success was defined as a decrease in point C <= 1/3 of the total vaginal length, point Ba and Bp <= -1, and without reoperation. Subjective success was defined as the absence of POP symptoms (vaginal weight or protrusion) and PGI-I (patient global impression of improvement) alternatives 1 and 2. The patients also responded to the Visual Analogue Scale (VAS) for satisfaction with the treatment and for pain, and ICIQ-VS for vaginal symptoms. The urodynamic study indication was individualized. The concomitant sling was performed when there was a diagnosis of stress or occult urinary incontinence. Result(s): Mean follow-up was 12 months. Baseline characteristics were similar between the groups. Mean age was 64 years, body mass index 26.7 and parity of 4.5 children. The overall objective success rate to date is 89.6% considering all compartments. One patient (1.16%) presented extrusion. 20.6% of non-preoperative continent patients developed DENOVO urinary incontinence and 66% required sling surgery during follow-up. The overall subjective success rate is 95.3% and so far no difference between groups. (Table Presented) Conclusion(s): The partial results do not show the statistical difference between the groups so far. The overall objective success rates are 89.6% and 95.3% of subjective success in the treatment of patients with advanced pelvic organ prolapseCopyright © European Association of Urology. Published by Elsevier B.V. All rights reserved.

Morelli, N., et al. (2021). "Essential amino acid supplement decreases liver fat in adolescents with pcos and obesity." Obesity (Silver Spring, Md.) 29(SUPPL 2): 12‐13.
	Background: Polycystic ovary syndrome (PCOS) is common and characterized by hyperandrogenism and oligomenorrhea. In adolescents with PCOS + obesity, insulin resistance is universal, and rates of hepatic steatosis (HS) are 2‐3 fold higher than in those without PCOS. HS is one of the best predictors for future development of type 2 diabetes. Essential amino acid (EAA) supplementation decreases intrahepatic triglyceride (IHTG) in aging and alcoholic fatty liver disease, but EAA effects on IHTG in youth with PCOS and obesity were unknown. Methods: In a double‐blind crossover placebo‐controlled trial in adolescents with PCOS and obesity, metabolic studies were performed after 28 days of twice daily placebo and EAA drinks. Measures included fasting labs, a 4‐hour oral sugar tolerance test (OSTT, 75 g of glucose and 25 g of fructose), IHTG by MRI, and body composition by DXA. Insulin resistance was estimated with HOMA‐IR for the fasted state and sensitivity was estimated with the oral minimal model during the OSTT. One sample t‐tests of change were used to assess treatment effects. Results: Twenty‐one girls with PCOS completed the study (BMI 37.3 ± 6.5 kg/m2 , age 15.6 ± 1.3 years). Weight (Δ 1 kg [‐1.8, 2.8]) and lean mass (Δ ‐0.03 kg [‐0.06, 0.01]) were unchanged with EAA supplementation. Following EAA, absolute IHTG decreased by 0.8% ± 1.3 (p = 0.013), which is a relative decrease of 7.5%. In those with HS at baseline (IHTG > 5.4%, N = 12), absolute IHTG decrease was ‐1.1% (‐1.8, ‐0.3) with a relative decrease ‐9.1% (‐1.5, ‐11.5). EAA supplementation decreased fasting triglycerides (‐16 mg/dL [‐36.5, ‐1], p = 0.019) and aspartate aminotransferase (AST) (‐3 U/L ± 3, p = 0.003). Decreased testosterone (‐3.0 ng/dL[‐8.5, ‐1.5], p = 0.066) was seen following EAA. Fasting insulin resistance (HOMA‐IR Δ ‐0.33 ± 2.1) and OSTT insulin sensitivity (Δ 3.67 × 10‐5 dl/kg/min per U/ml ± 1.28 × 10‐4) remained unchanged. Conclusions: Short‐term EAA supplementation decreases IHTG, serum TG and AST in adolescents with PCOS and obesity. No worsening of insulin sensitivity was noted, and in those with HS at baseline, the relative change of ‐9% approached clinical significance with just 1 month of treatment. Evaluation of the long‐term effects of EAA supplementation in PCOS with HS is needed, especially in youth where pharmacologic options are extremely limited.

Moreno, I., et al. (2024). "Impact of a Moderate CYP3A4 Inducer (Bosentan) on Lurbinectedin Pharmacokinetics and Safety in Patients with Advanced Solid Tumors: An Open-Label, Two-Way, Crossover, Phase Ib Drug-Drug Interaction Study." Pharmaceuticals 17(2): 182.
	This open-label, two-way, crossover, phase Ib drug-drug interaction study investigated whether the pharmacokinetics (PKs) and safety profile of lurbinectedin (LRB) are affected by co-administration of a moderate CYP3A4 inducer (bosentan, BOS) in adult patients with advanced solid tumors. Eleven patients were randomly assigned to Sequence 1 (LRB + BOS in Cycle 1 [C1] and LRB alone in Cycle 2 [C2]) or Sequence 2 (LRB alone in C1 and LRB + BOS in C2), and finally, eight patients (four per sequence) were considered evaluable for PK assessment. LRB (3.2 mg/m2, 1 h [h], intravenous) was administered alone or combined with multiple BOS administration (125 mg/12 h oral; 5.5 days). Co-administration with BOS decreased the systemic total exposure (area under the curve, AUC) of LRB by 21% for AUC0-t and 20% for AUC0- and increased clearance by 25%. Co-administration with BOS did not significantly modify the unbound plasma LRB PK parameters. BOS increased the conversion of LRB to its metabolite M1, with no changes on its metabolite M4. The LRB safety profile was consistent with the toxicities previously described for this drug. No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile.Copyright © 2024 by the authors.

Moreno-Acosta, P., et al. (2023). "hTERT and IGF-1R Proteins Expression in Response to Treatment in Patients with HPV Alpha 9-Positive Cervical Cancer." Radiation Research 199(5): 452-459.
	Human papillomavirus (HPV) infection is strongly associated with cervical cancer (CC). Genomic alterations caused by viral infection and subsequent dysregulation of cellular metabolism under hypoxic conditions could influence the response to treatment. We studied a possible influence of IGF-1Rb, hTERT, HIF1a, GLUT1 protein expression, HPV species presence and relevant clinical parameters on the response to treatment. In 21 patients, HPV infection and protein expression were detected using GP5+/GP6+PCR-RLB and immunohistochemistry, respectively. The worse response was associated with radiotherapy alone compared with chemoradiotherapy (CTX-RT), anemia and HIF1a expression. HPV16 type was the most frequent (57.1%) followed by HPV-58 (14.2%) and HPV-56 (9.5%). The HPV alpha 9 species was the most frequent (76.1%) followed by alpha 6 and alpha 7. IGF-1Rb (85.7%), HIF1a (61.9%), GLUT1 (52.3%), and hTERT expression [cytoplasm and nucleus (90.4%)] were detected. The MCA factorial map showed different relationships, standing out, expression of hTERT and alpha 9 species HPV, expression of hTERT and IGF-1Rb expression [Fisher's exact test (P 1/4 0.04)]. A slight trend of association was observed between, GLUT1 and HIF1 a expression, hTERT and GLUT1 expression. A noteworthy finding was the subcellular localization of hTERT in the nucleus and cytoplasm of CC cells and its possible interaction with IGF-1R in presence of HPV alpha 9 species. Our findings suggest that the expression of HIF1a, hTERT, IGF-1Rb and GLUT1 proteins that interact with some HPV species may contribute to cervical cancer development, and the modulation of treatment response. O 2023 by Radiation Research SocietyCopyright O2023 by Radiation Research Society. All rights of reproduction in any form reserved.

Moreno-Ligero, M., et al. (2023). "mHealth Intervention for Improving Pain, Quality of Life, and Functional Disability in Patients With Chronic Pain: Systematic Review." JMIR mHealth and uHealth 11: e40844.
	Background: Chronic pain (CP) is 1 of the leading causes of disability worldwide and represents a significant burden on individual, social, and economic aspects. Potential tools, such as mobile health (mHealth) systems, are emerging for the self-management of patients with CP.; Objective: A systematic review was conducted to analyze the effects of mHealth interventions on CP management, based on pain intensity, quality of life (QoL), and functional disability assessment, compared to conventional treatment or nonintervention.; Methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed to conduct a systematic review of randomized controlled trials (RCTs) published in PubMed, Web of Science, Scopus, and Physiotherapy Evidence Database (PEDro) databases from February to March 2022. No filters were used. The eligibility criteria were RCTs of adults (≥18 years old) with CP, intervened with mHealth systems based on mobile apps for monitoring pain and health-related outcomes, for pain and behavioral self-management, and for performing therapeutic approaches, compared to conventional treatments (physical, occupational, and psychological therapies; usual medical care; and education) or nonintervention, reporting pain intensity, QoL, and functional disability. The methodological quality and risk of bias (RoB) were assessed using the Checklist for Measuring Quality, the Oxford Centre for Evidence-Based Medicine Levels of Evidence, and the Cochrane RoB 2.0 tool.; Results: In total, 22 RCTs, involving 2641 patients with different CP conditions listed in the International Classification of Diseases 11th Revision (ICD-11), including chronic low back pain (CLBP), chronic musculoskeletal pain (CMSP), chronic neck pain (CNP), unspecified CP, chronic pelvic pain (CPP), fibromyalgia (FM), interstitial cystitis/bladder pain syndrome (IC/BPS), irritable bowel syndrome (IBS), and osteoarthritis (OA). A total of 23 mHealth systems were used to conduct a variety of CP self-management strategies, among which monitoring pain and symptoms and home-based exercise programs were the most used. Beneficial effects of the use of mHealth systems in reducing pain intensity (CNP, FM, IC/BPS, and OA), QoL (CLBP, CNP, IBS, and OA), and functional disability (CLBP, CMSP, CNP, and OA) were found. Most of the included studies (18/22, 82%) reported medium methodological quality and were considered as highly recommendable; in addition, 7/22 (32%) studies had a low RoB, 10/22 (45%) had some concerns, and 5/22 (23%) had a high RoB.; Conclusions: The use of mHealth systems indicated positive effects for pain intensity in CNP, FM, IC/BPS, and OA; for QoL in CLBP, CNP, IBS, and OA; and for functional disability in CLBP, CMSP, CNP, and OA. Thus, mHealth seems to be an alternative to improving pain-related outcomes and QoL and could be part of multimodal strategies for CP self-management. High-quality studies are needed to merge the evidence and recommendations of the use of mHealth systems for CP management.; Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42022315808; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=315808. (©Marta Moreno-Ligero, Jose A Moral-Munoz, Alejandro Salazar, Inmaculada Failde. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 02.02.2023.)

Moreno-Sepulveda, J., et al. (2022). "The Effect of Laparoscopic Endometrioma Surgery on Anti-Müllerian Hormone: A Systematic Review of the Literature and Meta-Analysis." JBRA Assisted Reproduction 26(1): 88-104.
	Objective: This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels.; Methods: This systematic review and meta-analysis included observational studies and randomized clinical trials published in English referenced in MEDLINE, SCOPUS and Cochrane (1982-2019). We included studies that reported AMH levels in the pre and post-operative period of patients undergoing laparoscopic surgery for endometrioma. Preoperative AMH was defined as the baseline AMH; short term AMH was measured no later than a month after surgery; medium term AMH was measured between one and six months after surgery; and long-term AMH was measured six or more months after surgery.; Results: Thirty-six studies met the inclusion criteria. A significant decrease was observed in short, medium and long-term post-operative AMH levels when compared with baseline AMH. However, there were no differences between short and long-term post-operative AMH levels, suggesting a non-significant recovery after one year of follow-up. A significant decrease in post-operative AMH was observed in bilateral endometriomas compared with unilateral cases. In addition, patients with endometriomas presented a significant decline in post-operative AMH compared with patients with other benign ovarian conditions. The decrease in post-operative AMH was significantly greater in bilateral cystectomy when compared with vaporization with bipolar energy or laser. We also observed a greater decrease in post-operative AMH with bipolar energy hemostasis compared with suture and hemostatic agents. These results should be taken with caution due to the high heterogeneity of the studies analyzed.; Conclusions: Endometrioma surgery has a deleterious effect on short, medium, and long-term post-operative AMH levels. Bilateral endometriomas and endometriomas greater than 7 cm have been associated with greater decreases in AMH. The mechanical resection of healthy tissue and the inflammatory damage on the ovarian cortex might explain the diminishing of ovarian reserve.

Morgan, O., et al. (2022). "Systematic Review of Comparisons Between Plastic and Silicone Dilators: Revealing a Knowledge Gap." Sexual Medicine Reviews 10(4): 513-519.
	Introduction: Vaginal stenosis is a distressing side effect of radiation therapy that can impair quality of life. Dilator therapy is an option for patients undergoing pelvic radiotherapy to mitigate vaginal stenosis. Currently, the dilators given to patients by most hospitals are made of plastic, compared to silicone dilators which are available on the market for purchase.; Objectives: We conducted a systematic literature review to find information to guide clinical recommendations to pelvic radiotherapy patients on potential differences regarding the use of plastic vs silicone dilators with regard to efficacy, cost, and patient preferences.; Methods: A systematic literature review was conducted in Embase, MEDLINE, and PubMed using Emtree terms. To be included in the review, papers needed to: focus on female patients undergoing radiation therapy, assess a vaginal dilator, measure any dilator intervention outcome, and specifically compare plastic vs silicone dilators for any measured outcome (either qualitative or quantitative).; Results: The initial search yielded 195 articles. Two area experts, with a third expert for arbitration, read each article and found that none met all review inclusion criteria. No studies were found that compared silicone to plastic dilators with regard to efficacy in treating vaginal stenosis due to radiation therapy, no studies were found that compared cost or cost-effectiveness of the 2 dilator types, and no studies were found comparing patient preferences or experiences (eg, comfort, adherence, ease of use) between the 2 dilator types.; Conclusion: The materials used to create dilators have never been rigorously compared in the context of radiotherapy-related vaginal stenosis. Institutions and patients have no data to guide their choice. Significantly more research at the patient and institutional level is needed to explore the potential long-term quality of life and cost benefits of improved adherence with silicone dilator use, and to guide shared decision-making regarding dilator choice.; Competing Interests: Conflict of Interest: The authors report no conflicts of interest. (Copyright © 2022, International Society for Sexual Medicine. Published by Elsevier.)

Morgan, R. D., et al. (2021). "Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial." The Lancet. Oncology 22(2): 277-288.
	BACKGROUND: Platinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported. We describe RECIST and Gynecologic Cancer InterGroup (GCIG) CA125 responses in patients receiving platinum-based neoadjuvant chemotherapy followed by DPS in the ICON8 trial. METHODS: ICON8 was an international, multicentre, randomised, phase 3 trial done across 117 hospitals in the UK, Australia, New Zealand, Mexico, South Korea, and Ireland. The trial included women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, life expectancy of more than 12 weeks, and newly diagnosed International Federation of Gynecology and Obstetrics (FIGO; 1988) stage IC-IIA high-grade serous, clear cell, or any poorly differentiated or grade 3 histological subtype, or any FIGO (1988) stage IIB-IV epithelial cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned (1:1:1) to receive intravenous carboplatin (area under the curve [AUC]5 or AUC6) and intravenous paclitaxel (175 mg/m2 by body surface area) on day 1 of every 21-day cycle (control group; group 1); intravenous carboplatin (AUC5 or AUC6) on day 1 and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 2); or intravenous dose-fractionated carboplatin (AUC2) and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 3). The maximum number of cycles of chemotherapy permitted was six. Randomisation was done with a minimisation method, and patients were stratified according to GCIG group, disease stage, and timing and outcome of cytoreductive surgery. Patients and clinicians were not masked to group allocation. The scheduling of surgery and use of neoadjuvant chemotherapy were determined by local multidisciplinary case review. In this post-hoc exploratory analysis of ICON8, progression-free survival was analysed using the landmark method and defined as the time interval between the date of pre-surgical planning radiological tumour assessment to the date of investigator-assessed clinical or radiological progression or death, whichever occurred first. This definition is different from the intention-to-treat primary progression-free survival analysis of ICON8, which defined progression-free survival as the time from randomisation to the date of first clinical or radiological progression or death, whichever occurred first. We also compared the extent of surgical cytoreduction with RECIST and GCIG CA125 responses. This post-hoc exploratory analysis includes only women recruited to ICON8 who were planned for neoadjuvant chemotherapy followed by DPS and had RECIST and/or GCIG CA125-evaluable disease. ICON8 is closed for enrolment and follow-up, and registered with ClinicalTrials.gov, NCT01654146. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 women were enrolled in ICON8, of whom 779 (50%) were planned for neoadjuvant chemotherapy followed by DPS. Median follow-up was 29·5 months (IQR 15·6-54·3) for the neoadjuvant chemotherapy followed by DPS population. Of 564 women who had RECIST-evaluable disease at trial entry, 348 (62%) had a complete or partial response. Of 727 women who were evaluable by GCIG CA125 criteria at the time of diagnosis, 610 (84%) had a CA125 response. Median progression-free survival was 14·4 months (95% CI 9·2-28·0; 297 events) for patients with a RECIST complete or partial response and 13·3 months (8·1-20·1; 171 events) for those with RECIST stable disease. Median progression-free survival for women with a GCIG CA125 response was 13·8 months (95% CI 8·8-23·4; 544 events) and 9·7 month (5·8-14·5; 111 events) for those without a GCIG CA125 response. Complete cytoreduction (R0) was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 women with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with a GCIG CA125 response and 30 (30%) of 101 women without a GCIG CA125 response. INTERPRETATION: The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient's clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response. FUNDING: Cancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

Morgan Robert, D., et al. (2023). "Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial." Clinical cancer research : an official journal of the American Association for Cancer Research 29(14): 2602-2611.
	Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.; Patients and Methods: Phase II trial with two entry points (EP1, EP2). Patients were recruited prior to rechallenge platinum. Patients with relapsed, gBRCAm-HGSOC were enrolled at EP1 if they were PARPi-naïve. Patients enrolled at EP2 had received their first course of olaparib prior to trial entry. EP1 patients were retreated with olaparib after RECIST complete/partial response (CR/PR) to platinum. EP2 patients were retreated with olaparib ± cediranib after RECIST CR/PR/stable disease to platinum and according to the platinum-free interval. Co-primary outcomes were the proportion of patients who received a second course of olaparib and the proportion who received olaparib retreatment for ≥6 months. Functional homologous recombination deficiency (HRD), somatic copy-number alteration (SCNA), and BRCAm reversions were investigated in tumor and liquid biopsies.; Results: Twenty-seven patients were treated (EP1 = 17, EP2 = 10), and 19 were evaluable. Twelve patients (63%) received a second course of olaparib and 4 received olaparib retreatment for ≥6 months. Common grade ≥2 adverse events during olaparib retreatment were anemia, nausea, and fatigue. No cases of MDS/AML occurred. Mean duration of olaparib treatment and retreatment differed (12.1 months vs. 4.4 months; P < 0.001). Functional HRD and SCNA did not predict PFS. A BRCA2 reversion mutation was detected in a post-olaparib liquid biopsy.; Conclusions: A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious. See related commentary by Gonzalez-Ochoa and Oza, p. 2563. (©2023 American Association for Cancer Research.)

Morgan Robert, D., et al. (2022). "c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial." BMC Medicine 20(1): 59.
	Introduction: Bevacizumab improves survival outcomes in women diagnosed with epithelial ovarian cancer (EOC). Pre-clinical data showed that the c-MET/VEGFR-2 heterocomplex negates VEGF inhibition through activation of c-MET signalling, leading to a more invasive and metastatic phenotype. We evaluated the clinical significance of c-MET and VEGFR-2 co-localisation and its association with VEGF pathway-related single nucleotide polymorphisms (SNPs) in women participating in the phase 3 trial, ICON7 (ClinicalTrials.gov identifier: NCT00262847).; Materials and Methods: Patients had FIGO stage I-IIA grade 3/poorly differentiated or clear cell carcinoma or stage IIB-IV epithelial ovarian, primary peritoneal or fallopian tube cancer. Immunofluorescence staining for co-localised c-MET and VEGFR-2 on tissue microarrays and genotyping of germline DNA from peripheral blood leukocytes for VEGFA and VEGFR-2 SNPs was performed. The significance of these biomarkers was assessed against survival.; Results: Tissue microarrays from 178 women underwent immunofluorescence staining. Multivariable analysis showed that greater c-MET/VEGFR-2 co-localisation predicted worse OS in patients treated with bevacizumab after adjusting for FIGO stage and debulking surgery outcome (hazard ratio [HR] 1.034, 95% confidence interval [95%CI] 1.010-1.059). Women in the c-MET/VEGFR-2 HIGH group treated with bevacizumab demonstrated significantly reduced OS (39.3 versus > 60 months; HR 2.00, 95%CI 1.08-3.72). Germline DNA from 449 women underwent genotyping. In the bevacizumab group, those women with the VEGFR-2 rs2305945 G/G variant had a trend towards shorter PFS compared with G/T or T/T variants (18.3 versus 23.0 months; HR 0.74, 95%CI 0.53-1.03).; Conclusions: In bevacizumab-treated women diagnosed with EOC, high c-MET/VEGFR-2 co-localisation on tumour tissue and the VEGFR-2 rs2305945 G/G variant, which may be biologically related, were associated with worse survival outcomes. (© 2022. The Author(s).)

Morice, P., et al. (2022). "Oncologic results of fertility sparing surgery of cervical cancer: An updated systematic review." Gynecologic Oncology 165(1): 169-183.
	Background: Several techniques can be proposed as fertility sparing surgery in young patients treated for cervical cancer but uncertaincies remain concerning their outcomes. Analysis of oncological issues is then the first aim of this review in order to evaluate the best strategy.; Results: Data were identified from searches of MEDLINE, Current Contents, PubMed and from references in relevant articles from January 1987 to 15th of September 2021. We carry out an updated systematic review involving 5862 patients initially selected for fertility-sparing surgery in 275 series.; Findings: In patients having a stage IB1 disease, recurrence rate/RR in patients undergoing simple conisation/trachelectomy, radical trachelectomy/RT by laparoscopico-vaginal approach, laparotomic or laparoscopic approaches are respectively: 4.1%, 4.7%, 2.4% and 5.2%. In patients having a stage IB2 disease, RR after neoadjuvant chemotherapy or RT by laparotomy are respectively 13.2% and 4.8% (p = .0035). After neoadjuvant treatment a simple cone/trachelectomy was carried out in 91 (30%) patients and a radical one in 210 (70%) cases. But the lowest pregnancy rate is observed in patients undergoing RT by laparotomy (36%).; Conclusions: The choice between these treatments should be based above all, on objective oncological data that strike a balance for each procedure between the best chances for cure and the fertility results. In patients having a stage IB1 disease, oncological results are quite similar according to the procedure used. In patients having a stage IB2 disease, RT by open approach has the lowest RR. Anyway the lowest pregnancy rate is observed in patients undergoing RT by laparotomy. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Morin, A., et al. (2022). "To Fight or to Flee? A Systematic Review of Ectopic Pregnancy Management and Complications During the Covid-19 Pandemic." In Vivo 36(4): 1570-1579.
	Background/Aim: During the COVID-19 pandemic, concerns regarding theoretical risks of surgery contributed to changes in clinical management to prevent contamination. We looked at the effect the pandemic had on the management of ectopic pregnancy. Our review compares published data on pre-COVID to COVID management of ectopic pregnancies and evaluates the differences where Early Pregnancy Unit (EPU) structures exist. Material(s) and Method(s): We performed a systematic review of the published evidence using a keyword strategy. The "Population Intervention Comparison and Outcome" (PICO) criteria were used to select studies. Three independent reviewers agreed on the data extracted after screening of the literature. The total population analysed included 3122 women. A meta-analysis of the included studies was completed using a random or fixed effect model depending on the heterogeneity (I2). Our outcomes were the following: type of management of ectopic pregnancy (EP), incidence of ruptured EP and rate of complications. We compared units with and without EPU infrastructure. Result(s): We included every study which recruited women diagnosed with ectopic pregnancy and compared the type of management during and prior the COVID-19 peak. Our literature search yielded 34 papers. 12 were included using the PRISMA guidelines. We observed no difference in the type of management (surgical versus non-surgical) [OR=0.99 (0.63-1.55), p=0.96, I2=77%] in the pre-Covid vs. Covid cohorts overall but a reduction of surgical management in EPU structures. There was no difference in the ectopic rupture rate within the EPU branch [OR=0.66 (0.33-1.31), p=0.24, I2=37%]. In contrast, in non-EPU (NPEU) structures there was a clear increased risk of ruptured ectopic pregnancy [OR=2.86 (1.84-4.46), p<0.01 I2=13%] and complications [OR=1.69 (1.23-2.31), p=0.001, I2=45%]. Conclusion(s): The risk of ruptured ectopic and complications was significantly higher in the absence of EPU structures. This worldwide trend was not reflected in the UK, where EPU systems are widespread, suggesting that EPU structures contributed to prompt diagnosis and safe management. In the post-COVID era, healthcare systems have come to realise that pandemics might become the norm and thus the onus is to identify services that have worked seamlessly.Copyright © 2022 International Institute of Anticancer Research. All rights reserved.

Morin, M., et al. (2021). "Transcranial direct current stimulation for provoked vestibulodynia: What roles do psychosexual factors play in treatment response?" Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 93: 54-60.
	There is growing evidence that provoked vestibulodynia (PVD), a frequent and debilitating condition, is characterized by central sensitization. This study aimed to examine predictive factors of transcranial direct current stimulation (tDCS) efficacy in this chronic pain population. Exploratory analysis derived from a randomized controlled trial was performed to assess predictors of pain reduction among 39 women with PVD who received 10 daily sessions of either active or sham tDCS. Clinical characteristics (e.g. pain intensity, duration and pain sensitivity) and psychosexual factors (e.g. pain catastrophizing, pain-related fear, anxiety, depressive symptoms and vaginal penetration cognitions) were assessed at baseline and used to predict tDCS response at 3-month follow-up. Analysis revealed that higher depressive symptoms and lower negative self-image cognitions were significant predictors of pain reduction at follow-up and accounted for 62.3% of the variance in the active tDCS group. Higher genital incompatibility cognitions were related to poorer response, regardless of treatment group. These findings suggest that women with PVD presenting higher depressive symptoms and lower levels of negative self-image cognitions could derive greater benefits from tDCS. These results suggest that tDCS could be effective in a subgroup of women with PVD - a possibility worth exploring with future prospective larger studies.

Morin, M., et al. (2022). "A Randomized Prospective Pilot Study Investigating the Feasibility and Effects of High Intensity Laser Therapy for Women with Vulvodynia." Journal of Sexual Medicine 19(Supplement 3): S1.
	Introduction Laser therapy and more specifically, High Intensity Laser Therapy (HILT), is an emerging non-invasive and non-ablative treatment modality, that appears promising for treating provoked vestibulodynia (PVD). However, evidence supporting this treatment remains limited so far as no prospective study has examined the feasibility, acceptability and effects in women with PVD. Objective 1) to evaluate the feasibility and acceptability of HILT in women with PVD and 2) to explore the effects of active and sham HILT on pain intensity during intercourse. Methods Women aged 18-45 years suffering from PVD participated in this randomized pilot study. Women were included if they reported pain at the entry of the vagina during vaginal intercourse (intensity of >=5 on a numerical rating scale (NRS)) for more than three months. A standardized pelvic examination was performed by a gynecologist from our team to confirm the eligibility of participants. Women were randomized to receive bi-weekly sessions of active (n=20) or sham HILT (n=20) for 6 weeks. Women were assessed at baseline and post-treatment (2 weeks after the end of the treatment). Patients, outcome assessors and data analysts were blinded to group assignation. The attendance rate at laser sessions (>=80% of participants attending >=10 sessions), the dropout rate (<15%) and the absence of serious adverse events served as feasibility and acceptability outcomes and benchmarks. Patients' perceived improvement and satisfaction were also assessed. The effects of treatment on mean pain intensity during intercourse were measured. Results A total of 45 women were screened by the gynecologist and 40 were enrolled in the study (n=5 were excluded because of other diagnoses i.e. infection, dermatological conditions). Among the women included, only one participant in the real HILT group dropped out of the study at post-treatment due to time constraints. Regarding the attendance rate for treatment, the 12 sessions were completed by all participants, except for two women who had 11 sessions due to Covid-related reasons. No serious side effects were observed in either group. In regard to patients' global impression of change, 79% of women reported significant improvement in the active HILT group as opposed to 47% in the sham group. In the sham group only, 10% reported worsening of their condition. Regarding satisfaction to treatment, women in the active group were more satisfied with a mean of 6.6/10 (SD 2.8) compared to 4.6/10 (SD 3.1) in the sham group (p<0.05). A significant reduction in pain from baseline to post-treatment was found for women in the active HILT group (baseline 7.3+/-1.3; post-treatment 4.1+/-2.2; p<.001) and sham HILT group (baseline 7.4+/-1.6; post-treatment 5.4+/-3.2; p=.002). Conclusions HILT is a feasible and acceptable intervention to treat women with PVD. With the significant improvements observed, findings support conducting a randomized controlled trial to confirm the efficacy of this promising intervention.

Morlans-Lanau, M., et al. (2022). "Establishing midwife-led continuity of care interventions in perinatal mental health in high-risk pregnancies: a best practice implementation project." JBI evidence implementation 20(S1): S49-S58.
	Objectives: The current best practice implementation project aimed to improve the quality of continuity of care and emotional well-being in women with high-risk pregnancies.; Introduction: Perinatal mental health disorders, such as perinatal depression and anxiety, are considered major health issues and are associated with poor maternal and neonatal outcomes. Women with high-risk pregnancies are considered a group of women with a substantial vulnerability and the value of continuity of care is vital in this group.; Methods: The current project used the pre-post implementation clinical audit following the JBI Evidence Implementation framework. A baseline audit and a follow-up audit were conducted involving 120 high-risk pregnant women in a hospital's obstetric unit. An intervention was performed establishing a midwife consultation and a referral circuit for the different healthcare professionals. A screening was performed through several validated questionnaires.; Results: To reflect the continuum of care, three topics were selected, including antenatal psychosocial assessment, intrapartum care and postpartum depression assessment, with a total of 10 criteria. The baseline audit results showed 0% compliance in all the criteria since the proposed standards of care did not exist before the audit. After the implementation of the strategies, the compliance achieved 100% in all audit criteria. A multidisciplinary hospital guideline was established for standardized care and mental well-being care for high-risk pregnant women.; Conclusion: Follow-up in the mental health of pregnant women is insufficient. Improving emotional well-being in pregnancy should be a target of clinical practice. More national and international guidelines to assess mental well-being during pregnancy and the postpartum period should be developed. (Copyright © 2022 JBI. Unauthorized reproduction of this article is prohibited.)

Moro, E., et al. (2019). "The Impact of Hormonal Replacement Treatment in Postmenopausal Women with Uterine Fibroids: A State-of-the-Art Review of the Literature." Medicina (Kaunas, Lithuania) 55(9).
	Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Material(s) and Method(s): Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Result(s): Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusion(s): For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.

Morozov, A. O., et al. (2023). "[Efficiency and safety of Prostatex in patients with chronic prostatitis/chronic pelvic pain syndrome. Results of the phase IV PRESTIGE trial]." Urologiia (Moscow, Russia : 1999)(2): 41-47.
	Introduction: A large number of both preclinical and clinical studies demonstrates the efficiency of bioregulatory peptides for the treatment of prostatitis and chronic pelvic pain syndrome (CPPS). A relatively new drug in this group is Prostatex, the active ingredient of which is bovine prostate extract.; Aim: To evaluate the effect of taking Prostatex on the intensity of CPPS, the sexual function, and the results of microscopy of expressed prostate secretions and urinalysis.; Materials and Methods: A cohort of patients aged 25-65 years with chronic abacterial prostatitis and complaints of chronic pelvic pain was analyzed. The abacterial type of prostatitis was confirmed by bacteriological examination of expressed prostate secretions. The patients received Prostatex for 30 days according to the following scheme: 1 suppository rectally 1 time per day. The follow-up was 30 days. Before starting the drug and at the end of the 30-day course, patients completed the Chronic Prostatitis Symptom Index (NIH-CPSI) and the sexual function questionnaire. In addition, urinalysis and microscopic study of expressed prostate secretions was performed.; Results: A total of 1700 patients were included in the study. While taking the drug, there was a significant decrease in pain during digital rectal examination, as well as in the intensity of pain as a symptom of CPPS. The severity of symptoms after treatment was lower in all domains of NIH-CPSI. Microscopic study of the expressed prostate secretions during treatment showed a decrease in the number of patients with excessive number of leukocytes. The sexual function improved, while urinalysis and microscopy of expressed prostate secretions returned to the reference values.; Conclusion: The use of Prostatex for the treatment of patients with CPPS reduces the severity of pain and other symptoms of chronic prostatitis, increases sexual function and normalizes the expressed prostate secretions and urinalysis. In order to obtain data of a higher level of evidence, it is necessary to carry out randomized, blind, placebo-controlled studies.

Morres, I. D., et al. (2022). "Exercise for perinatal depressive symptoms: A systematic review and meta-analysis of randomized controlled trials in perinatal health services." Journal of Affective Disorders 298: 26-42.
	Background: Exercise improves perinatal depressive (PD) symptoms, but reports call for more robust evidence. This systematic review and meta-analysis aimed at synthesizing evidence exclusively from randomized controlled trials (RCTs) examining the effects of exercise on PD symptoms in women recruited through perinatal health services. Method(s): Nine e-databases and fifteen systematic reviews were searched for relevant RCTs. Exercise-specific tools extracted/coded data. A meta-analysis using a random effects model (Standardized Mean Difference [SMD]) investigated the effects of exercise on PD scores post-intervention. Result(s): From 285 records, 14 RCTs (2.025 participants) were considered eligible including two RCTs with clinically diagnosed PD women. Exercise showed a statistically significant, small, overall antidepressant effect (SMD = -0.21, 95% CI = -0.31, -0.11, p = 0.0001) with low/non-significant heterogeneity (Q = 17.82, I 2 = 16%, p = 0.27). Only the fail-safe criterion recorded marginally significant publication bias, but trim-fill analysis added no study. Sensitivity analyses increased the overall effect in RCTs showing lower risk of bias or delivering >=150 min/week moderate intensity aerobic exercise. Subgroup analyses revealed significant antidepressant effects for exercise across various settings, delivery formats, depressive symptoms severities and outcome measures used. Heterogeneity was low/non-significant in all analyses (I 2 <= 50%). Hedges' g corrections did not influence the results. Limitation(s): Study limitations include the small number of available trials and clinically diagnosed PD samples and the variety of exercise modalities. Conclusion(s): Exercise improved PD symptoms, especially in RCTs with lower risk of bias or with >=150 min/day moderate intensity aerobic exercise interventions. Findings are clinically useful but more RCTs for clinically diagnosed PD women are needed for firmer conclusions.Copyright © 2021 Elsevier B.V.

Morris Georgina, C., et al. (2022). "Outcomes and experiences of using oral voriconazole with or without concomitant topical agents to treat refractory vulvovaginal yeast infections." International journal of STD & AIDS 33(13): 1134-1141.
	Background: We describe 11 cases of refractory vulvovaginal yeast infections (RVVYI) treated using oral voriconazole with or without concomitant topical agents.; Methods: Retrospective case-note review of all women prescribed oral voriconazole to treat RVVYI in five Sexual Health Clinics from Jan 2010-March 2020. Demographic details, clinical features, diagnostic results and treatment outcomes were collected.; Results: 11 women with vulvovaginal symptoms for a median of 1 year were treated with voriconazole. RVVYI was diagnosed clinically and confirmed on microscopy and culture with speciation. 10/11 isolates were fluconazole resistant, 1 intermediately sensitive, 10/11 were either fully or intermediately sensitive to voriconazole. All had received prior fluconazole and clotrimazole and 10/11 had used at least 2-weeks of one or more second-line antifungals with non-clearance of the yeast. Oral voriconazole 400 mg BD day-1, then 200 mg BD 13-days was prescribed and 10/11 women completed the course. Concomitant topical treatment was used by 6/11. Liver and renal function were monitored at 0, 7, 14 days. One woman stopped voriconazole after 5-days due to perioral tingling. Other transient side-effects were nausea ( n = 2), photosensitivity, muscle aches, hair thinning (all n = 1), peripheral visual disturbance ( n = 2). 8/11 experienced both symptom reduction and yeast clearance. Two women had an initial partial response but experienced resolution of symptoms following a second course of voriconazole.; Conclusions: Our observational data adds to the limited evidence to support voriconazole treatment for RVVYI. A 2-week course of voriconazole was tolerated and completed by 10/11 women. Eight women, five using concomitant topical agents, achieved mycological cure.

Morris, M. H., et al. (2021). "A Nurse-Navigated, Postpartum Support Text Messaging Intervention: satisfaction Among Primiparous Women." Journal of perinatal & neonatal nursing 35(4): 330‐339.
	More than 50% of maternal deaths in the United States occur during the first year following childbirth. Nearly 40% of these deaths occur between days 1 and 41 of the postpartum period. Historically, women receive less attention from healthcare providers during the postpartum period when compared with the care provided during pregnancy and childbirth. Women may not return for scheduled follow‐up care until 4 to 6 weeks after birth, if they return at all. The role of postpartum nurse navigator (PPNN) was developed to deliver a novel, text messaging intervention as part of a randomized controlled trial to 43 primiparous women who experienced an unplanned cesarean birth. Through daily, interactive text messaging, the PPNN assessed study participants' general well‐being, assisted with symptom navigation, offered anticipatory guidance, and provided informational support until 4 weeks postpartum. Satisfaction with the intervention was evaluated using a survey that incorporated quantitative and qualitative responses. Overwhelmingly, 93% of participants rated their overall experience with the text messaging intervention as outstanding or good. At least 95% of the participants indicated that they would likely choose to receive daily text messaging from a PPNN following a subsequent birth. Convenient access to professional nurse support for women postbirth warrants further evaluation.

Morrison, J. (2023). "Neoadjuvant chemotherapy for ovarian cancer: Avoiding 'needless hurt'?" BJOG : an international journal of obstetrics and gynaecology 130(13): 1589-1590.
	
Morrison Zachary, D., et al. (2019). "A systematic review of management options in pediatric rectal prolapse." Journal of pediatric surgery 54(9): 1782-1787.
	Purpose: Rectal prolapse is a relatively common condition in infants and young children with a multifactorial etiology. Despite its prevalence, there remains clinical equipoise with respect to secondary treatment in pediatric surgery literature. We conducted a systematic review to evaluate methods of secondary treatment currently used to treat rectal prolapse in children.; Methods: We searched Pubmed, Medline, and Scopus with the terms "rectal prolapse" and "children" for papers published from 1990 to April 2017. Papers satisfying strict criteria were analyzed for patient demographics, intervention, efficacy, and complications. Procedures were grouped by like type. Pooled success rates were calculated.; Results: Twenty-seven studies documenting 907 patients were included. Injection sclerotherapy had an overall initial success rate of 79.5%. Ethyl alcohol seemed the best sclerosing agent due to a high first-injection success rate, low complication rate, and ready accessibility. Several perineal repairs were found, with operative success rates ranging from 60.8%-100%. Laparoscopic rectopexy with mesh was the most commonly reported transabdominal procedure and had an overall success rate of 96.1%. Postoperative complications from all procedures were comparable.; Conclusion: Though many secondary treatment options have been reported for rectal prolapse, sclerotherapy and laparoscopic rectopexy predominate in contemporary literature and appear to have high success and low complication rates.; Level of Evidence: IV. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Morrow, A. L., et al. (2022). "Mechanisms Underlying Recovery From Postpartum Depression Following Brexanolone Therapy." Biological psychiatry 91(3): 252-253.
	
Morssinkhof, M. W. L., et al. (2020). "Associations between sex hormones, sleep problems and depression: A systematic review." Neuroscience and biobehavioral reviews 118: 669-680.
	Sleep problems and depression are both common and have a high impact on quality of life. They are also strongly associated and commonly occur together. During the reproductive age, both sleep problems and depression are almost twice as common in women than men. Epidemiological studies show that women experience more sleep problems and depressive symptoms around times when sex hormones change, such as puberty and menopause, but it is unclear what effect sex hormones have on sleep problems and depression. This systematic review aims to summarize and evaluate studies that investigated the relationship between sex hormones, sleep and depression. Systematic search resulted in 2895 articles, of which 13 met inclusion criteria. Depressed patients showed worse sleep than controls, but no significant difference in endogenous hormone levels was found. Additionally, higher endogenous estrogen was associated with better sleep in controls, but associations between endogenous sex hormones and depressive symptoms were inconclusive. More research on the effect of sex hormones on sleep and depression is necessary.

Mortensen Olivia, E., et al. (2022). "The evidence behind the use of LASER for genitourinary syndrome of menopause, vulvovaginal atrophy, urinary incontinence and lichen sclerosus: A state-of-the-art review." Acta Obstetricia et Gynecologica Scandinavica 101(6): 657-692.
	In recent years, LASER has been introduced as a minimally invasive treatment for a broad range of vaginal and vulvar symptoms and diseases. However, the efficacy and safety of vaginal and vulvar LASER has continuously been questioned. The aim of this study is to create an overview of the current literature and discuss the controversies within the use of LASER for genitourinary syndrome of menopause, vulvovaginal atrophy, urinary incontinence and lichen sclerosus. A search string was built in PubMed. The search was commenced on August 25, 2021 and closed on October 27, 2021. Two authors screened the studies in Covidence for inclusion according to the eligibility criteria in the protocol. The data were extracted from the studies and are reported in both text and tables. This review included 114 papers, of which 15 were randomized controlled trials (RCTs). The effect of LASER as a vaginal treatment was investigated for genitourinary syndrome of menopause in 36 studies (six RCTs), vulvovaginal atrophy in 34 studies (four RCTs) and urinary incontinence in 30 studies (two RCTs). Ten studies (three RCTs) investigated the effect of vulvar treatment for lichen sclerosus. Half of the included RCTs, irrespective of indication, did not find a significant difference in improvement in women treated with vaginal CO 2 or Er:YAG LASER compared with their respective controls. However, most non-comparative studies reported significant improvement after exposure to vaginal or vulvar LASER across all indications. Included studies generally had a short follow-up period and only a single RCT followed their participants for more than 6 months post treatment. Adverse events were reported as mild and transient and 99 studies including 51 094 patients provided information of no serious adverse events. In conclusion, this review found that the effect of vaginal and vulvar LASER decreases with higher study quality where potential biases have been eliminated. We therefore stress that all patients who are treated with vaginal or vulvar LASER should be carefully monitored and that LASER for those indications as a treatment should be kept on a research level until further high-quality evidence is available. (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Morteza, T., et al. (2021). "Triplet aprepitant/dexamethasone/ondansetron versus doublet dexamethasone/ondansetron for prevention of moderately emetogenic chemotherapy: a placebo-controlled, double-blind, randomized clinical trial of efficacy." European journal of clinical pharmacy 23(2): 89‐97.
	Background: This randomized, placebo‐controlled, double‐blind study aimed to evaluate the efficacy of adding aprepitant to standard antiemetic regimens for the prevention of chemotherapy‐induced nausea and vomiting (CINV) caused by moderately emetogenic chemotherapy (MEC) regimens. Method: One hundred and sixty eligible patients who were scheduled to receive MEC regimens for the first time were randomized to receive either triplet (aprepitant, dexamethasone, ondansetron) or doublet (dexamethasone, ondansetron and placebo) anti‐emetic medications. The primary endpoint was to determine the proportion of patients who experienced CINV within 120 hours after the chemotherapy commencement. Secondary endpoints were complete response (CR) of overall phase (OP), correlation between CR of the OP with the CR of acute phase, and the effect of aprepitant on subsequent cycle of chemotherapy. Results: There was a trend towards decreasing nausea from 13% to 5% (p = 0.12), and vomiting from 8% to 1% (p = 0.084). Moreover, aprepitant increased CR rates from 91% to 98% in the overall phase (p = 0.08). For the second cycle of chemotherapy in which all patients received the standard anti‐emesis protocol (the doublet) the rate of CR in OP was correlated with aprepitant use in the first cycle of chemotherapy (p = 0.01). Conclusion: In patients receiving MEC regimens, aprepitant decreased nausea and vomiting and increased complete response rates on different phases of the first cycles of treatment, although these differences did not reach statistical significance. However, using aprepitant in the first cycle significantly increased overall phase complete response rate of the second cycle of treatment.

Morton, M., et al. (2023). "Evaluation of Efficacy and Adverse Events After Second Immunotherapy Exposure in Endometrial and Cervical Carcinoma." Obstetrics and Gynecology 142(2): 360-363.
	Immunotherapy has changed the treatment paradigm for gynecologic malignancies. The RUBY (NCT03981796) and NRG-GY018 (NCT03914612) studies have shown significant improvements in survival for immunotherapy in combination with chemotherapy in advanced and recurrent endometrial cancer, and immunotherapy likely will become the first-line standard-of-care therapy. However, the efficacy of repeated exposure to immunotherapy for gynecologic cancers is unknown. In this retrospective series, 11 patients with endometrial cancer and four patients with cervical cancer were identified who received subsequent immunotherapy after first immunotherapy. With subsequent immunotherapy, three patients (20.0%) had complete response, three (20.0%) had partial response, three (20.0%) had stable disease, and six (40.0%) had disease progression; progression-free survival was similar to first-line immunotherapy. These data provide proof of concept for subsequent treatment with immunotherapy in gynecologic cancers, specifically endometrial cancer.; Competing Interests: Financial Disclosure Casey Cosgrove has received funds from AstraZeneca and GlaxoSmithKline. Floor Backes has received research funding from Merck, Eisai, ImmunoGen, Clovis Beigene, Natera, and Tempus, and serves as a consultant for Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, and Myriad. David O'Malley receives institutional research funding from AbbVie, Agenus, Aravive, AstraZeneca, Boston Biomedical, Clovis Oncology, Eisai, Exelixis, Genmab, GOG Foundation, ImmunoGen, IOVANCE Biotherapeutics, Leap Therapeutics, Merck, Mersana Therapeutics, NRG Oncology, OncoQuest, Precision Therapeutics, Regeneron Pharmaceuticals, Rubuis Therapeutics, Sutro Biopharma, TESARO, Advaxis, Alkermes, Arcus Biosciences, BeiGene, Bristol Myers Squibb, Deciphera Pharma, EMB Serono, Genentech, GlaxoSmithKline, Hoffman-La Roche, Incyte Corporation, Karyopharm, Ludwig Institute, Merck Sharp & Dohme Corp, NCI, NovoCure, OncoC4 Inc, Pfizer Inc, Prelude Therapeutics, RTOG, Seattle Genetics (SeaGen), SWOG, and Verastem Inc. David O'Malley receives consulting fees from AbbVie, Adaptimmune, Agenus Inc, Arquer Diagnostics, Arcus Biosciences Inc, AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Bio, Eisai, Elevar, Exelixis, Genentech Inc, Genelux, GlaxoSmithKline, GOG Foundation, Hoffman-La Roche Inc, ImmunoGen Inc, Imvax, InterVenn, INXMED, IOVANCE Biotherapeutics, Janssen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics Inc, Luzsana Biotechnology, Merck & Co, Merck Sharp & Dohme Corp, Mersana Therapeutics Inc, Myriad, Novartis, NovoCure, OncoC4 Inc, Onconova, Regeneron Pharmaceuticals Inc, Repimmune, R Pharm, Roche Diagnostics, Seattle Genetics (SeaGen), Sorrento, Sutro Biopharma, Tarveda Therapeutics, Toray, Trillium, Umoja, Verastem Inc, VBL Therapeutics, Vincerx Pharma, Xencor, and Zentalis. The other authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Morton, M., et al. (2023). "Clinical trial participation is associated with improved overall survival in women with recurrent platinum resistant epithelial ovarian cancer (003)." Gynecologic Oncology 176(Supplement 1): S4.
	Objectives: The objective of this study was to investigate whether clinical trial participation impacts overall survival (OS) in women with platinum-resistant epithelial ovarian cancer (EOC). Method(s): An IRB-approved, retrospective single-institution cohort study was performed on women with platinum-resistant EOC from January 1, 2009, to December 31, 2017. Platinum resistance was defined as progression within 6 months after completion of platinum chemotherapy. Women were divided into two cohorts: 1) clinical trial participants (CTP) for platinum resistant EOC or 2) no CTP. The impact of trial participation on overall survival (OS) from the date of platinum resistance was assessed with univariate and multivariate models. Result(s): Of 305 eligible women with recurrent platinum resistant EOC, 46 (15.1%) were CTP. There were no significant differences in age (mean 61.2 vs 63.3 years, P = 0.21), BMI (mean 27.5 vs 27.6 kg/m2, P = 0.90), race (P = 0.61), medical comorbid conditions (P > 0.05) and ECOG performance status (P = 0.07) for CTP versus no CTP. The majority of patients underwent primary cytoreduction at diagnosis (76.1% vs 69.1%, P = 0.0.34) with no differences in residual disease (P = 0.27) or HIPEC (6.5% vs 6.6%, P = 0.99) for CTP versus no CTP patients. CTP patients were exposed to a greater number of prior therapy lines as compared to no CTP (5 vs 4 lines, P <= 0.001). There was no difference in PARP inhibitor use (21.7% vs 15.1%, P = 0.26), bevacizumab (22.2% vs 32.1%, P = 0.31), or intraperitoneal chemotherapy (13.3% vs 14.3%, P = 0.86) for CTP versus no CTP. On univariate analysis, CTP was associated with significantly improved OS from the date of platinum resistance compared to no CTP (Median survival 12.7 vs 10.5 months, HR: 1.45, 95% CI: 1.03-2.03, P = 0.04). Conclusion(s): In this retrospective cohort of women with platinum resistant EOC, clinical trial participation was associated with improved OS compared to no trial participation. Availability and participation in clinical trials should be prioritized in women with recurrent, platinum resistant EOC. [Formula presented]Copyright © 2023

Morton, V. H., et al. (2023). "Monofilament Suture Versus Braided Suture Thread to Improve Pregnancy Outcomes After Vaginal Cervical Cerclage (C-STICH): a Pragmatic Randomized, Controlled, Phase 3, Superiority Trial." Obstetrical & gynecological survey 78(4): 199‐200.
	
Mosavi, S., et al. (2023). "Icariin, a novel promising complementary therapeutic strategy in the management of female infertility: A literature review." Galen Medical Journal 12: e2528.
	The prevalence of pre-menopausal female infertility is increasing considerably due to various causes such as environmental pollutants, increased administration of chemotherapeutics and radiation exposure, microbial infections, and genetic/epigenetic alterations. However, the current therapeutical strategies remain unfavorite as the disadvantages are strongly challenging. Icariin (ICI) is a phytoestrogen that exerts some promising properties in order to alleviate female infertility. Therefore, the current literature review aimed to evaluate the conducted studies regarding the beneficial impacts of ICI on the female reproductive system and female fecundity. The findings of the present study revealed that ICI is able to modulate the levels of reproductive hormones as it causes a significant decrement in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) while increasing the levels of estrogen and progesterone. Furthermore, the administration of ICI results in a dramatic alteration in the expression of sex steroids receptors, particularly in female reproductive tissues. In addition, preserving ovarian follicular reserve, improving the ovarian and uterine histoarchitecture, elongating the estrous cycle duration, and eventually advancing the female fecundity are other major effects of ICI on the female reproductive system. Despite these desired beneficial properties, the current knowledge appears to be insufficient, hence further investigations, particularly on humans, are encouraged. To the best of our knowledge, this review provides a comprehensive information regarding the beneficial effects of ICI on female infertility for the firs time.[GMJ.2023;12:e2528].Copyright © 2023 Shiraz University of Medical Sciences. All rights reserved.

Mosch, A., et al. (2022). "Early removal of indwelling catheter and vaginal pack after vaginal prolapse surgery; A retrospective cohort study in a teaching hospital in The Netherlands." International Urogynecology Journal 33(Supplement 1): S26-S27.
	Introduction: After pelvic organ prolapse (POP) surgery a vaginal pack and indwelling bladder catheter are inserted to absorb excess blood loss, reduce haematoma formation and a retention bladder. However, late removal of the vaginal packs and indwelling catheter increases the risk of urinary tract infection and prolonged hospital stay. Therefore, the optimal duration of the bladder catheters and vaginal packing in situ after POP surgery remains controversial. Objective(s): The objective of this study was to compare early removal (3 hours post-operatively) of indwelling catheter and vaginal pack after vaginal POP surgery to removal the morning after surgery regarding urinary retention, haematomas and duration of hospital stay. Method(s): This retrospective cohort study was performed in the gynaecology department of a teaching hospital in the Netherlands between January 1, 2019 and December 31, 2020. The follow up was 6 weeks. In 2019 the vaginal pack and bladder catheter were removed at 6 a.m. the day after surgery (group 1) and in 2020 the vaginal pack and catheter were removed 3 hours post-surgery (group 2). If patients could not void or had a post-void residual volume (PVR) of more than 150ml, a new catheter was placed or clean intermittent catheterization (CIC) was started until they did not have urinary retention. If patients had a PVR > 150ml at time of discharge, they were discharged with either CIC a indwelling catheter. The main outcome measures were post-operative spontaneous voiding, recatheterization or CIC because of urinary retention during hospital stay and after discharge, vaginal hematomas and duration of hospital stay. Numerical variables were evaluated using unpaired student's t-test and mean +/- SD was calculated. Categorical variables were described as frequencies and percentages and evaluated by chi-square analyses. A p-value <0,05 was considered statically significant. Result(s): In 2019 174 patients were included (group 1) and in 2020 108 (group 2). Baseline characteristics were similar between groups. There was no significant difference between group 1 and group 2 with respect to post-operative spontaneous voiding after removal (respectively 126 patients (72.4%) and 69 patients (64.5%), p=0.16), spontaneous voiding a day after removing catheter and vaginal pack (153 patients (87.9%) and 91 patients (84.1%), p=0.36). Recatheterization or CIC during hospital stay and/or discharge because of urinary retention (48 patients (27.6%) and 38 patients (35.5%), p=0.16), discharge with a catheter or CIC (21 patients (12.1%) and 17 patients (15.9%), p=0.36), vaginal hematomas (4 (2.3%) and 2 (1.9%), p=0.81) and duration of hospital stay in days (1.08 +/- 0.64 and 0.99 +/- 0.49, p=0.21) were also not statistically significant different between group 1 and group 2. Conclusion(s): Removing the indwelling catheter and vaginal pack 3 hours after vaginal pelvic organ prolapse surgery does not lead to more postoperative complications such as urinary retention and hematomas compared to removal the morning after surgery. Therefore, early removal is a feasible and safe alternative for the current clinical practise of removal the indwelling catheter the morning after POP surgery.

Moscow City Oncology Hospital, N. (2021). SENTRY Tailoring Postoperative Management Through Sentinel Lymph Node Biopsy in Low- and Intermediate-Risk Endometrial Cancer.
	No Results Available Procedure: Laparoscopic total hysterectomy with bilateral salpingo-oophorectomy and sentinel lymph node biopsy Change in postoperative treatment strategy|Adjustments in FIGO staging|Bilateral SLN detection|Details of intraoperative complications of SLN biopsy|The rate of intraoperative complications of SLN biopsy|Major postoperative morbidity|Postoperative mortality|Incidence of lymphedema|Pelvic recurrence rate|Time to pelvic recurrence Female Not Applicable 102 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MCOH62-07-08-21 March 1, 2025

Moshkalova, G., et al. (2023). "Endometrial thickness and live birth rates after IVF: a systematic review." Acta bio-medica : Atenei Parmensis 94(3): e2023152.
	Aim: This study aims to systematically review the current literature on published studies with data on the clinical significance of endometrial thickness on ultrasound for live birth rates after IVF or intracytoplasmic sperm injection (ICSI).; Methods: An extensive systematic review of PubMed, Web of Science, ScienceDirect, Google Scholar, and Open Gray databases, and following hand-search of the reference list of the included studies was performed.; Results: We found 20 eligible studies that evaluated 20 546 patients for endometrial thickness, presented risk factors for decreased endometrial receptivity, and IVF outcomes with fresh and frozen embryo transfer (FET) cycles. The mean age of the patients ranged from 28.86 to 41.03 years. Reported endometrial thickness ranged from <4 mm to >15 mm. The clinical pregnancy rate varied from 9,09% to 61,49% in fresh embryo transfer cycles and from 13,3% to 79,31% in FET cycles. Overall, LBR varied between 4,80% and 48,99% in fresh embryo cycles and between 6.06% and 39,19% in FET cycles.; Limitations: Only English-language studies were included; most studies were from the China region; retrospective study design used in most studies; different ET thresholds, which in turn could significantly alter the correlation with pregnancy outcomes; different IVF procedure protocols in fresh or FET cycles.; Conclusions: IVF outcomes in patients with impaired endometrial receptivity do not depend only on the condition of the endometrium. Risk factors and endometrial thickness significantly affect LBR in fresh and FET cycles.

Moskvicheva, L. I. (2023). "MINIMALLY-INVASIVE AND NON-INVASIVE METHODS OF THERMAL DESTRUCTION IN THE TREATMENT OF PATIENTS WITH AGGRESSIVE FIBROMATOSIS." Siberian Journal of Oncology 22(5): 96-104.
	The purpose of the study was to characterize various methods of local physical destruction used in the treatment of patients with aggressive fibromatosis and demonstrate international experience of their use. Material and Methods. Literature search was conducted in the electronic databases RSCI (Russian Science Citation Index) and NCBI (National Centre for Biotechnology Information) in the interval time between 2002 and 2022. The review was devoted to the thermal ablation modalities (radiofrequency, microwave ablation, cryodestruction, high-intensity focused ultrasound ablations) used in therapy of patients with desmoid fibromas of various locations, as well as their safety and efficacy. Results. The review presents the current data on safety and efficacy of minimally-invasive and non-invasive methods of hypo-and hyperthermic local destruction in patients with aggressive fibromatosis, gives the characteristics of exposure and biological effects when performing radiofrequency and microwave ablation, cryodestruction, high-intensity focused ultrasound therapy, describes the main limitations of the methods, indications and contraindications for their application, as well as the methods of prevention of the development of desmoid fibromas. Conclusion. The described methods of local destruction are used in clinical practice mainly for palliative and symptomatic purposes, in case of persistent tumor growth or recurrence, ineffectiveness of other treatment options or contraindications to them due to concomitant somatic pathology or functional status of the patient. Inclusion of these methods in the treatment plan of patients with aggressive fibromatosis can contribute to the reduction of pain syndrome, improvement of functional status of patients as well as long survival with no evidence of tumor progression.Copyright © 2023, Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved.

Mosorin, M.-E., et al. (2023). "Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial." Journal of Clinical Medicine 12(8).
	This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased ( p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min ( p = 0.011) and AUCglucose ( p = 0.018) increased in the CVC group. Fasting insulin levels ( p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride ( p < 0.001) and hs-CRP ( p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.

Moss Katrina, M., et al. (2022). "What happens after menopause? (WHAM): A prospective controlled study of symptom profiles up to 12 months after pre-menopausal risk-reducing salpingo-oophorectomy." Gynecologic Oncology 167(1): 58-64.
	Objective: Understanding how symptoms cluster after premenopausal risk-reducing salpingo-oophorectomy (RRSO) can inform patient expectations but information is lacking. We aimed to identify symptom profiles after RRSO, changes over time, and the effect of hormone therapy (HT).; Method: Participants were premenopausal women from a longitudinal controlled study (What Happens After Menopause? (WHAM)). Menopausal symptoms were prospectively measured in three groups: pre-menopausal comparisons who retained their ovaries (n = 99), RRSO HT users (n = 57) and RRSO non-HT users (n = 38). Symptoms (hot flashes, night sweats, low desire, vaginal dryness, poor sleep, anxiety/depression) were measured at baseline (pre-surgery) and at 3, 6 and 12 months using standardised questionnaires. Latent transition analysis was used to identify symptom profiles post-RRSO, and the probability of changing profiles over time.; Results: Three symptom profiles were identified: Most Symptoms (81-87% non-HT; 36-41% HT; 7-9% comparisons), Few Symptoms (7-13% non-HT; 36-42% HT; 77-80% comparisons), and Sexual Symptoms (0-10% non-HT; 17-27% HT; 14-15% comparisons). Most of the non-HT group reported Most Symptoms at 3 months with only a 2% chance of improvement by 12 months. The HT group were split between profiles at 3 months with a 5-13% chance of improvement by 6 months (14% chance of worsening), and a 12-32% chance of improvement by 12 months (4-25% chance of worsening).; Conclusions: Symptoms cluster into distinct profiles after premenopausal RRSO. Most non-HT users are highly symptomatic with little chance of improvement by 12 months. In contrast, two-thirds of HT users have fewer symptoms and a much higher chance of improvement. These findings can inform patient decision-making and expectations.; Competing Interests: Declaration of Competing Interest None of the funding agencies had a role in the design or conduct of the study, nor the collection, management, analyses or interpretation of the data, nor the preparation or approval of this manuscript. MH is an editor for the Cochrane Collaboration Group and has received pharmaceutical funding from QUE Oncology P/L, Madorra P/L and Ovoca Bio (Australia) P/L for clinical trials outside of the submitted work. KM, EOK and GM do not have any conflict of interest to declare. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mossack, S., et al. (2022). "A Randomized Controlled Trial Comparing Telemedicine Versus In-Person Office Visits for the Follow-Up of Overactive Bladder." Urogynecology (Philadelphia, Pa.) 28(12): 819‐824.
	IMPORTANCE: Overactive bladder is a condition that may be ideally suited for the use of telemedicine because initial treatment options are behavioral modification and pharmacotherapy. OBJECTIVE: We sought to evaluate if there was an overall difference in patient follow‐up rates between telemedicine and in‐person visits. STUDY DESIGN: New patients presenting with overactive bladder from July 2020 to March 2021 were randomized into telemedicine and in‐person visits groups. A prospective database was maintained to compare follow‐up rates, satisfaction rates, and time commitment. RESULTS: Forty‐eight patients were randomized, 23 to the telemedicine group and 25 to the in‐person visits group. There was no significant difference in follow‐up rates between the telemedicine and in‐person follow‐up groups at 30 days (39% vs 28%, P = 0.41), 60‐days (65% vs 56% P = 0.51) or 90 days (78% vs 60%, P = 0.17). There was no significant difference in satisfaction rates between the 2 groups. There was a significant difference between the average telemedicine visit time and in‐person visit time (12.1 ± 6.9 minutes vs 22.8 ± 17.1 minutes; P = 0.02). For in‐person visits, the average travel time was 49 minutes (interquartile range, 10‐90 minutes) and average miles traveled was 22.1 miles (interquartile range, 10‐70 miles). CONCLUSIONS: There was no significant difference in follow‐up or satisfaction rates between telemedicine and in‐person visits. Telemedicine visits took half the length of time compared with in‐person visits. On average, patients in the telemedicine group saved approximately 1 hour per follow‐up visit. Telemedicine visits save both the health care provider and patient significant amounts of time without sacrificing patient satisfaction and follow‐up rates.

Mosseri, J., et al. (2024). "Margin status after loop electrosurgical excision procedure (LEEP) and laser excision in patients with high-grade cervical neoplasia." Journal of Gynecology Obstetrics and Human Reproduction 53(1): 102707.
	Introduction: Early management of high-grade cervical intraepithelial neoplasia is one of the key steps in cervical cancer prevention after vaccination and screening. It relies on lesion removal by surgical excision, and the French National Cancer Institute (INCa) in 2016 recommend using a loop electro excision procedure (LEEP). However, the laser excision method seems to be as effective with similar rates of negative excision margins and postoperative clearance of HPV. Objective(s): The main objective of our study was to compare the laser excision method to LEEP by evaluating the quality of the surgical margins. We also studied factors associated with the status of the margins and the depth of cones. Method(s): We conducted a retrospective unicentric study between 2009 and 2017. Result(s): Two hundred and thirty-one patients were included: 154 laser excisions and 77 LEEP. Negative surgical margin was achieved in 69.5 % of laser excisions and 72.7 % of LEEP (p = 0.649). Concerning factors predicting margin status, only a greater cone depth was associated with negative margins (OR: 0.91 (95 %CI: 0.84, 0.89); p = 0.02). The surgical technique was not found to be associated with the status of the margins (OR: 0.85 (95 %CI: 0.46,1.56); p = 0.61). Concerning factors predicting cone depth, only the LEEP was associated with a shorter cone depth (OR: 0.24 (95 %CI: 0.08, 0.69); p 0.008). Significant results are based on univariate analysis. Conclusion(s): No difference was found between the two technics concerning the rate of negative margins. However, LEEP seems to be associated with shorter cone depth in this study.Copyright © 2023

Mosseri, J., et al. (2022). "Laser conization for cervical intraepithelial neoplasia: Effectiveness and obstetric outcomes." Journal of Gynecology Obstetrics and Human Reproduction 51(4): 102341.
	Purpose: To evaluate the effectiveness and obstetric outcomes after laser conization for cervical intraepithelial neoplasia. Method(s): This retrospective study included 757 patients who underwent laser conization between 2014 and 2020. Patients with a diagnosis of invasive lesions or adenocarcinoma in situ were excluded. Histological data from the conization specimen, pre and postoperative histological and virological data (Human PapillomaVirus (HPV) test) and obstetric outcomes were collected from the medical record. The primary endpoint was the negative surgical margin rates after laser conization. The secondary endpoint were the size of the operative specimen, the postoperative virological test results (3 to 6 months after surgery), factors associated with negative or positive margin and postoperative obstetric outcomes (prematurity). Patient characteristics and outcomes were compared using Student's t-test, chi2 test, or Fisher exact test. Values of p <= 0.05 were considered significant. Result(s): This study included 757 patients. Negative surgical margins were obtained in 76.1% of the cases and were associated with more negative HPV tests at 6 months (64.9% vs. 52.5%, p = 0.006) and fewer repeat surgeries (0.2% vs. 2.2%, p = 0.013) than for patients with positive margins. Among the patients under 43 years at the time of conization, 71 achieved a pregnancy with a term >22 weeks, and of these 66 (93%) delivered at term (>=37 weeks). Conclusion(s): Laser conization appears to be an effective technique for the management of cervical intraepithelial neoplasia both in terms of the quality of the resection margins and the obstetric prognosis.Copyright © 2022 Elsevier Masson SAS

Mostafa, M., et al. (2023). "Curative effect of HIFU in management of different types of ectopic pregnancy: a systematic review."
	
Moszynski, R., et al. (2022). "Using a Modified Polysaccharide as a Hemostatic Agent Results in Less Reduction of the Ovarian Reserve after Laparoscopic Surgery of Ovarian Tumors-Prospective Study." Medicina (Kaunas, Lithuania) 59(1).
	Background and Objectives : The study investigated whether the method of achieving hemostasis affects the ovarian reserve in patients undergoing laparoscopic surgery due to ovarian tumors or cysts. Materials and Methods : Patients with unilateral tumors or ovarian cysts, who qualified for laparoscopic tumor enucleation, were randomly selected to receive modified polysaccharides or bipolar coagulation. Ovarian reserve was analyzed by anti-Mullerian hormone (AMH) level. Results : The study included 38 patients: 19 patients in the modified polysaccharide group and 19 in the bipolar coagulation group. Patients after bipolar coagulation treatment had statistically significantly lower AMH 6 months after surgery compared to the group treated with modified starch. The levels of AMH in the study and control groups were 3.96 +/- 2.12 vs. 2.51 +/- 1.39 ng/mL, respectively; p = 0.018. A statistically significant decrease in AMH was also demonstrated in the bipolar coagulation group as compared to the preoperative assessment ( p = 0.049). There was no statistically significant decrease in AMH in the group of patients treated with the modified starch. Conclusions : Using a modified polysaccharide during laparoscopic cystectomy is effective and has a positive effect on the ovarian reserve compared to the use of bipolar coagulation. Both the AMH level 6 months after surgery and the percentage decrease in AMH were more favorable in the group of patients treated with modified starch.

Motan, T., et al. (2023). "Directive clinique no 435: Chirurgie minimalement invasive dans les traitements de fertilite." Journal of Obstetrics and Gynaecology Canada 45(4): 283-293.e282.
	Objectif: Evaluer les risques et benefices de la chirurgie minimalement invasive dans la prise en charge des patientes atteintes d'infertilite et fournir des conseils aux gynecologues qui prennent en charge les problemes les plus frequents chez ces patientes. Population cible: Patientes atteintes d'infertilite (incapacite a concevoir apres 12 mois de rapports sexuels non proteges) en processus diagnostique ou sous traitement. Benefices, risques et couts: On peut recourir a la chirurgie de la reproduction minimalement invasive pour traiter l'infertilite, ameliorer les resultats des traitements de fertilite ou preserver la fertilite. Toutes les interventions chirurgicales comportent des risques et des complications associees. La chirurgie de la reproduction n'ameliore pas toujours la fertilite et peut, dans certains cas, compromettre la reserve ovarienne. Toutes les interventions entrainent des couts, lesquels sont assumes par la patiente ou son assureur. Donnees probantes: Des recherches ont ete faites dans les bases de donnees PubMed-Medline, Embase, Science Direct, Scopus et Cochrane Library pour repertorier les articles publies en anglais dans la periode de janvier 2010 a mai 2021 (voir les termes de recherche MeSH a l'annexe A). Methodes de validation: Les auteurs ont evalue la qualite des donnees probantes et la force des recommandations en utilisant le cadre methodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe B en ligne (tableau B1 pour les definitions et tableau B2 pour l'interpretation des recommandations fortes et conditionnelles [faibles]). Professionnels concernes: Gynecologues qui prennent en charge les affections courantes chez les patientes atteintes d'infertilite. DECLARATIONS SOMMAIRES: 1. La laparoscopie est utile pour determiner l'etiologie de l'infertilite si l'imagerie pelvienne revele des resultats normaux (moyenne). 2. Les cliniciens doivent remettre en question la valeur therapeutique de la laparoscopie si les traitements de fertilite sont accessibles et reporter la laparoscopie jusqu'a ce que les traitements s'averent inefficaces (elevee). 3. En cas d'endometriose minime ou legere, la resection ou l'ablation des lesions augmente significativement la probabilite d'une conception spontanee (moyenne). 4. Par extrapolation, il faudrait traiter par laparoscopie au moins 20 patientes atteintes d'infertilite inexpliquee pour obtenir 1 conception spontanee supplementaire (elevee). 5. Chez les patientes ayant subi plusieurs cycles de fecondation in vitro infructueux, la laparoscopie peut ameliorer la probabilite de grossesse cumulative en augmentant la probabilite d'une conception spontanee (faible). 6. Les fibromes de type 0 a 2 (sous-muqueux) d'apres le systeme de stadification de 2011 de la Federation internationale de gynecologie et d'obstetrique (FIGO) et les fibromes intramuraux qui deforment la cavite uterine risquent de nuire a la fertilite (moyenne). 7. On ignore si l'ablation des fibromes de type 3 a7 selon la FIGO (sans deformation de la cavite) augmente la probabilite de grossesse apres traitement de fertilite (faible). 8. La myomectomie laparoscopique peut etre preferable a la laparotomie selon le nombre et la taille des fibromes et l'experience du chirurgien (faible). 9. La reparation chirurgicale des trompes de Fallope avec obstruction distale peut ameliorer la probabilite d'une grossesse spontanee, mais augmente aussi le risque de grossesse ectopique (faible). 10. L'excision ou la ligature de l'hydrosalpinx unilateral peut ameliorer la probabilite d'une grossesse spontanee (faible). 11. La reparation chirurgicale ou la recanalisation de la trompe avec obstruction proximale donnent une probabilite de grossesse spontanee de 33 a 61 % (faible). 12. L'ablation des kystes ovariens benins non endometriosiques peut compromettre la reserve ovarienne, mais a un moindre degre que l'excision d'endometriomes (moyenne). 13. Le forage ovarien laparoscopique semble aussi efficace que les gonadotrophines pour induire l'ovulation et obtenir une grosse se clinique, mais cette intervention peut reduire la probabilite d'une naissance vivante (faible). 14. La transposition ovarienne avant radiotherapie semble ameliorer la probabilite d'une fonction ovarienne residuelle (moyenne). 15. La transposition ovarienne peut etre moins benefique chez les femmes de plus de 30 ans (faible). 16. La grossesse spontanee et la naissance vivante sont possibles apres une transposition ovarienne (tres faible). 17. Il faut considerer le benefice d'ameliorer la fecondite par rapport aux risques de compromettre la reserve ovarienne lorsqu'on envisage le traitement laparoscopique de l'endometriose ovarienne et des endometriomes (elevee). 18. La laparoscopie ne doit pas etre consideree comme le traitement de premiere intention de l'infertilite associee a l'endometriose (elevee). 19. La resection laparoscopique des endometriomes, comparativement au drainage et/ou a l'ablation, offre une meilleure diminution du risque de recurrence, mais augmente le risque de compromettre la reserve ovarienne (moyenne). RECOMMANDATIONS: 1. La laparoscopie ne doit pas etre offerte systematiquement dans l'evaluation initiale de l'infertilite inexpliquee (forte, elevee). 2. La laparoscopie peut etre offerte a une patiente jeune apres des traitements de fertilite infructueux (forte, elevee). 3. La laparoscopie peut etre offerte a une patiente atteinte d'infertilite inexpliquee et ayant connu plusieurs cycles infructueux de fecondation in vitro (conditionnelle, faible). 4. La myomectomie est envisageable chez les patientes ayant des fibromes de type 0 a 2 (sous-muqueux) selon la FIGO et une infertilite inexpliquee, en particulier si elle se soumet a des traitements de fertilite (conditionnelle, faible). 5. La myomectomie est deconseillee chez les patientes asymptomatiques ayant des fibromes de type 3 a 7 selon la FIGO (sans deformation de la cavite) dans le seul but d'ameliorer la probabilite de conception spontanee (conditionnelle, faible). 6. La myomectomie ne doit pas etre realisee dans le seul but de reduire le risque d'avortement spontane (conditionnelle, faible). 7. Il est recommande de reserver l'intervention chirurgicale dans la portion distale de la trompe aux patientes pour qui la fecondation in vitro n'est pas accessible (conditionnelle, faible). 8. L'excision ou la ligature de l'hydrosalpinx avant le transfert de l'embryon augmente significativement la probabilite de grossesse (forte, elevee). 9. L'ablation des kystes ovariens non endometriosiques dans le seul but d'ameliorer la fertilite n'est pas recommandee (conditionnelle, moyenne). 10. La laparoscopie est la voie recommandee pour la kystectomie ovarienne (conditionnelle, moyenne). 11. Les sutures et les colles hemostatiques sont preferables a la cauterisation bipolaire pour assurer l'hemostase pendant une kystectomie (conditionnelle, faible). 12. Le forage ovarien laparoscopique peut etre envisage chez les patientes atteintes d'un syndrome des ovaires polykystiques resistant aux agents oraux si les gonadotrophines ne sont pas accessibles (conditionnelle, moyenne). 13. Il y a lieu d'envisager la transposition ovarienne chez les patientes devant subir une radiotherapie pelvienne afin d'ameliorer la fonction ovarienne post-traitement (conditionnelle, moyenne). 14. Avant d'entreprendre une transposition ovarienne prealable a la radiotherapie pelvienne, il y a lieu d'envisager l'orientation de la patiente vers un fertologue et la possibilite d'une cryoconservation d'ovules ou d'embryons. Bien que les grossesses spontanees et les naissances vivantes soient possibles apres une transposition ovarienne, cette intervention rend difficile l'acces aux ovaires par voie vaginale aux fins de fecondation in vitro. Il est egalement fort probable que la radiotherapie pelvienne rende l'environnement uterin inapte a porter une grossesse, ce qui necessite le recours a la gestation pour autrui (conditionnelle, faible). 15. Bien que le traitement laparoscopique ne soit pas un traitement de premiere intention de l'infertilite associee a l'endometriose, on peut l'offrir aux pa ientes atteintes d'endometriose avec histoire d'infertilite si elles presentent d'autres indications pour la chirurgie (p. ex., douleur); les conseils doivent aussi prendre en compte l'age de la patiente, la duree de l'infertilite et la reserve ovarienne (conditionnelle, faible). 16. Il faut bien informer les patientes du risque que le traitement chirurgical des endometriomes compromette la reserve ovarienne (forte, elevee). 17. La resection laparoscopique des endometriomes est indiquee en cas d'inquietude quant a l'acces aux follicules pour le prelevement d'ovules dans un processus de fecondation in vitro (moyenne, faible).Copyright © 2023

Motzer Robert, J., et al. (2022). "Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies." Expert Review of Anticancer Therapy 22(4): 383-400.
	Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has shown efficacy and manageable safety across multiple cancer types. The recommended starting doses for lenvatinib differ across cancer types and indications based on whether it is used as monotherapy or as combination therapy.; Areas Covered: This review covers clinical trials that established the dosing paradigm and efficacy of lenvatinib and defined its adverse-event profile as a monotherapy; or in combination with the mTOR inhibitor, everolimus; or the anti-PD-1 antibody, pembrolizumab; and/or chemotherapy.; Expert Opinion: Lenvatinib has been established as standard-of-care either as a monotherapy or in combination with other anticancer agents for the treatment of radioiodine-refractory differentiated thyroid carcinoma, hepatocellular carcinoma, renal cell carcinoma, and endometrial carcinoma, and is being investigated further across several other tumor types. The dosing and adverse-event management strategies for lenvatinib have been developed through extensive clinical trial experience. Collectively, the data provide the rationale to start lenvatinib at the recommended doses and then interrupt or dose reduce as necessary to achieve required dose intensity for maximized patient benefit. The adverse-event profile of lenvatinib is consistent with that of other tyrosine kinase inhibitors, and clinicians are encouraged to review and adopt relevant symptom-management strategies.

Mou, T., et al. (2023). "Cost-effectiveness of Prophylactic Retropubic Sling at the Time of Vaginal Prolapse Surgery." Obstetrical and Gynecological Survey 78(3): 148-149.
	
Mou, T., et al. (2023). "Minimally invasive burch colposuspension to reduce de novo stress incontinence: the micro randomized trial." American Journal of Obstetrics and Gynecology 228(3 Supplement): S819-S820.
	Objectives: To determine whether the addition of minimally-invasive (MIS) Burch colposuspension is superior to no incontinence procedure during MIS sacrocolpopexy in stress-continent subjects with pelvic organ prolapse for decreasing postoperative de novo stress urinary incontinence (SUI). Material(s) and Method(s): In this randomized superiority trial, we recruited stress-continent subjects undergoing MIS sacrocolpopexy with negative empty supine cough stress tests. Subjects were randomized to receive either concomitant Burch or no Burch (control). Physical exams, PFDI-20, and PISQ-12 were completed at baseline and at 12-weeks after surgery in a blinded manner. The primary outcome was the composite measure of postoperative de novo SUI at 12-weeks that included (1) "Yes" to Question #17 on the PFDI-20, (2) positive retrofill cough stress test, and (3) any SUI treatment after sacrocolpopexy. Using data from the CARE trial, a sample size of 42 participants would demonstrate that the addition of a Burch was superior to control with a superiority margin of 15% lower in composite de novo SUI rate, 80% power, and type 1 error of 0.05. Assuming a 15% dropout rate, a total of 50 subjects were enrolled. Primary analyses used an intention-to-treat approach, and secondary analyses were per protocol. All missing values were set as "failure," or positive urinary findings. Result(s): From February 2019 to September 2022, 50 subjects underwent randomization with 26 assigned to Burch and 24 as controls (Figure). Twelve weeks after surgery, 50% of the subjects in Burch group and 41.7% of controls met one or more of the criteria for de novo SUI (p=0.555). There was no difference between Burch and control groups in symptoms of urinary frequency, urgency incontinence, or urinary retention at 12-weeks (Table). The Burch group had a significantly longer operative time when compared to the control group [+69-minute; 95%CI 41-96; p<.001], but there was no difference in estimated blood loss or void trial results. There was no difference in anterior vaginal wall support between Burch and control groups [-3(-3 to -3) vs -3(-3 to -3), p=0.237] nor in responses to the 3 subscales from PFDI-20 or PISQ-12 at 12-weeks. Conclusion(s): Among stress-continent subjects after MIS sacrocolpopexy, the addition of laparoscopic Burch was not superior to no Burch in preventing postoperative de novo SUI at 12-weeks postop. [Formula presented] Image. Enrollment and disposition of patients in the MICRO randomized trial [Formula presented] Table. Twelve-weeks postoperative urinary outcomesCopyright © 2022

Moubarak, M., et al. (2022). "Re-treatment with PARPi in patients with recurrent epithelial ovarian cancer: A single institutional experience." Gynecologic Oncology Reports 40: 100939.
	Introduction: We aimed to evaluate real-life experiences with the re-challenge of poly(ADP-Ribose)Polymerase (PARP) inhibitors (PARPi) after a prior PARPi therapy in patients with recurrent EOC. Method(s): A retrospective descriptive study was conducted at a tertiary care center of excellence for ovarian cancer. Demographic, pathological, and therapeutic data were collected for patients with recurrent epithelial ovarian cancer who were re-treated with PARPi in their therapy course. Result(s): Twenty-nine patients were included in the study. Twenty-six patients received the second PARPi as maintenance therapy after two different lines of therapy and three patients received the second PARPi as upfront therapy after progression. Most of the patients (57.7%) were exposed to first PARPi after a second-line therapy. The median progression-free survival under the first and second PARPi therapy was estimated at 15 and 7 months respectively. PFS under the second PARPi after platinum-based chemotherapy was better after a complete remission with a median PFS of 8.5 months, compared to patients with partial remission (5.5 months). A better PFS was noted in case of negative BRCA status under the second PARPi therapy (median PFS of 7.4 vs. 4.5 months, p = 0.11). The second PARPi therapy was mainly discontinued due to disease progression (84.6% of the cases). Discontinuation of treatment with the second PARP due to toxicity was needed in one case who developed a myelodysplastic syndrome. Conclusion(s): Real-life data support prospective evidence that patients with recurrent EOC may derive benefit of the re-treatment with PARPi in case of clear response to the last platinum-based therapy.Copyright © 2022

Moufarrij, S. and E. O'Cearbhaill Roisin (2023). "Novel Therapeutics in Ovarian Cancer: Expanding the Toolbox." Current oncology (Toronto, Ont.) 31(1): 97-114.
	Despite high response rates to initial therapy, most patients with ovarian cancer will ultimately recur and go on to develop resistance to standard treatments. Novel therapies have been developed to overcome drug resistance and alter the tumor immune microenvironment by targeting oncogenic pathways, activating the innate immune response, and enhancing drug delivery. In this review, we discuss the current and future roles of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, bevacizumab, and mirvetuximab in the treatment of ovarian cancer. We explore the emerging role of therapeutic targets, including DNA repair pathway inhibitors and novel antibody-drug conjugates. Furthermore, we delve into the role of immunotherapeutic agents such as interleukins as well as immune-promoting agents such as oncolytic viruses and cancer vaccines. Innovative combination therapies using these agents have led to a rapidly evolving treatment landscape and promising results for patients with recurrent ovarian cancer.

Moufarrij, S., et al. (2023). "Assessing the need for venous thromboembolism prophylaxis at the time of neoadjuvant chemotherapy for ovarian cancer: A literature review." Gynecologic Oncology 170: 167-171.
	Objective: Gynecologic cancers, especially ovarian cancer, are associated with a high incidence of venous thromboembolism (VTE). Recent data have shown the risk of VTE development is not only limited to the postoperative period; there also appears to be an increased risk during neoadjuvant chemotherapy (NACT) administration, prompting the need for better risk stratification in this setting. We sought to assess the risk of VTE development in patients with ovarian cancer undergoing NACT.; Methods: We performed a PubMed literature review using the following medical terms: advanced ovarian cancer, advanced peritoneal cancer, advanced fallopian tube cancer, thrombosis, thromboembolic events, and neoadjuvant chemotherapy. Eligible studies included patients with advanced ovarian, fallopian tube, or peritoneal cancer who underwent NACT and had VTE. VTE was defined as either a deep venous thrombosis or a pulmonary embolism.; Results: Seven relevant studies were identified; all 7 were published between 2017 and 2021. Across these studies, we identified 1427 patients who underwent NACT and either had VTE at presentation or developed VTE during their treatment course. Of these patients, 1171 underwent NACT and were at risk for VTE development and were included in our pooled analysis. Of these patients, 144 (12.3%) developed VTE.; Conclusions: VTE prophylaxis may be considered in patients with ovarian cancer undergoing NACT.; Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Jewell reports personal fees from Covidien/Medtronic. All other authors have no potential conflicts of interest to disclose. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Moufawad, G., et al. (2023). "Cervicovaginal fibroids: a systematic review for a comprehensive management plan." Italian Journal of Gynaecology and Obstetrics 35(2): 176-183.
	Objective. Leiomyomas are the most common benign tumours of the female genital tract. However, cervical leiomyomas are rare, with a prevalence of only 0.6%. The aim of this article is to provide a general treatment plan in the management of cervical leiomyomas and the special considerations to be accounted for, such as hymen integrity and size limits. Materials and Methods. We performed a systematic review about the argument cervical leiomyomas. A total of 19 articles were included. Results. The location of cervicovaginal leiomyomas near important organs and vessels makes the approach to their management more critical. Traditionally, a vaginal approach was considered the gold standard for cervicovaginal myomectomy. However, hymen integrity in some societal cultures makes a vaginal approach more difficult. It is for this reason that surgeons usually switch to traditional laparotomy or, more recently, to laparoscopy. Conclusions. With the advancement in endoscopy and its application in gynaecologic surgery, laparoscopy has become a feasible option. In addition, the size of the cervicovaginal leiomyoma is a determining factor for the management approach and choice of appropriate surgical technique.Copyright © 2023.

Moujaber, T., et al. (2022). "New therapeutic opportunities for women with low-grade serous ovarian cancer." Endocrine-Related Cancer 29(1): R1-R16.
	Low-grade serous ovarian cancer (LGSC) is a morphologically and molecularly distinct subtype of ovarian cancer, accounting for ~10% of serous carcinomas. Women typically present at a younger age and have a protracted clinical course compared with the more common, high-grade serous ovarian cancer. Currently, the primary treatment of LGSC is the same as other epithelial ovarian cancer subtypes, with treatment for most patients comprised of debulking surgery and platinum/taxane chemotherapy. Primary surgical cytoreduction to no visible residual disease remains a key prognostic factor; however, the use of platinum-based chemotherapy in both upfront and relapsed setting is being questioned due to low response rates in LGSC. Most LGSC expresses steroid hormone receptors, and selected patients may benefit from endocrine maintenance therapy following chemotherapy, in particular, those with evidence of residual disease at completion of surgery. In the recurrent setting, while hormonal therapies may offer disease stabilisation with relatively low toxicity, objective response rates remain low. Strategies to increase response rates, including combining with CDK4/6 inhibitors, are being investigated. LGSC has a high prevalence of activating somatic mutations in mitogen-activated protein kinase pathway genes, most commonly in KRAS, BRAF and NRAS. Trametinib, a MEK inhibitor, has shown efficacy over chemotherapy and endocrine therapy. The use of combination targeted therapies, immunotherapy and anti-angiogenic agents, remain active areas of investigation for the treatment of LGSC. Copyright © 2021 Society for Endocrinology Published by Bioscientifica Ltd. Printed in Great Britain

Moukarzel, L. A., et al. (2021). "Non-exenterative surgical management of recurrent endometrial carcinoma." Gynecologic Oncology 162(2): 268-276.
	OBJECTIVE: To examine the role of non-exenterative secondary cytoreductive surgery (SCS) compared with non-surgical treatments and identify predictors of improved survival for patients with recurrent endometrial cancer (EC). METHODS: All patients undergoing primary surgical management for EC 1/1/2009-12/31/2017 who subsequently developed recurrence were retrospectively identified. Survival was determined from date of diagnosis of first recurrence to last follow-up and estimated using Kaplan-Meier method. Differences in survival were analyzed using Log-rank and Wald tests, based on Cox Proportional Hazards model. RESULTS: Among 376 patients with recurrent EC, median time to recurrence was 14.3 months (range, 0.2-102.2), post-recurrence median survival 29 months, median follow-up 29.2 months (range, 0-116). Sixty-one patients (16.2%) received SCS, 257 (68.4%) medical management (MM) (chemotherapy and/or radiation therapy), 32 (8.5%) hormonal therapy, 26 (6.9%) no further therapy. Patients selected for SCS were younger, had more endometrioid histology, more stage I disease at initial diagnosis, no residual disease after primary surgery, longer interval to first recurrence or progression, and the longest OS (57.6 months) (95% CI, 33.3-not reached). On multivariate analysis SCS was an independent predictor of improved survival. Among the 61 SCS patients, age < 70 at time of initial diagnosis, and endometrioid histology, were associated with improved post-relapse survival univariately (p = 0.008, 0.03, respectively). CONCLUSIONS: While MM was the most common treatment for first recurrence of EC, patients selected for surgery demonstrated the greatest survival benefit even after controlling for tumor size, site, histology, stage, time to recurrence. Careful patient selection and favorable tumor factors likely play a major role in improved outcomes. Surgical management should be considered whenever feasible in medically eligible patients, with additional consideration given to our suggested criteria.

Moukarzel Lea, A., et al. (2022). "Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues." Gynecologic Oncology 165(2): 239-247.
	Objective: To determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues.; Methods: Normal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting.; Results: RNA-sequencing revealed 4231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value <0.05). Gene enrichment analyses demonstrated that the most significantly upregulated genes in normal tissues played a role in immune as well as heat shock response (both adjusted p < 0.001). In contrast, HIPEC induced an increased expression of primarily heat shock response and protein folding-related genes in tumor tissues (both adjusted p < 0.001). HIPEC-induced heat shock protein (HSP) expression changes, including in HSP90, HSP40, HSP60, and HSP70, were also observed at the protein level in both normal and tumor tissues.; Conclusions: HIPEC with carboplatin resulted in an upregulation of heat shock-related genes in both normal and tumor tissue, with an additional immune response gene induction in normal and protein folding in tumor tissue. The findings of our exploratory study provide evidence to suggest that HIPEC administration may suffice to induce gene expression changes in residual tumor cells and raises a biological basis for the consideration of combinatorial treatments with HSP inhibitors.; Competing Interests: Declaration of Competing Interest G. Zoppoli reports receiving travel grants from Roche, Novartis, and Pfizer, consultation fees from Pfizer, reagents from ThermoFisher Scientific and Cytiva Life Sciences, outside the submitted work. N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution, outside the current study. J.S. Reis-Filho reports receiving personal/consultancy fees from Goldman Sachs, REPARE Therapeutics and Paige.AI, membership of the scientific advisory boards of VolitionRx, REPARE Therapeutics and Paige.AI, membership of the Board of Directors of Grupo Oncoclinicas, and ad hoc membership of the scientific advisory boards of Roche Tissue Diagnostics, Ventana Medical Systems, Novartis, Genentech and InVicro, outside the scope of this study. J.S. Reis-Filho has stocks or stock options with REPARE Therapeutics and Paige.AI. D.S. Chi reports membership of the medical advisory boards of Bovie Medical Co. (now Apyx Medical), Verthermia Inc. and Biom ‘Up, to have/had stock options of Bovie Medical Co. (now Apyx Medical), Verthermia Inc., Intuitive Surgical Inc. and TransEnterix Inc., and to be the Chief Editor and shareholder of C Surgeries. D. Zamarin reports personal/consulting fees from Agenus, Hookipa Biotech, Western Oncolytics, Synthekine, Mana Therapeutics, Xencor, Memgen and Takeda, grants and personal fees from Merck and from Astra Zeneca, grants and non-financial support from Genentech, grants from Plexxikon and stock options from Calidi Biotherapeutics, outside the submitted work. D. Zamarin has a patent for use of Newcastle Disease Virus for cancer therapy, outside the submitted work. Dr. Aghajanian reports membership of advisory boards/personal fees from Tesaro, Eisai/Merck, Mersana Therapeutics, Roche/Genentech, Abbvie, AstraZeneca/Merck, Repare Therapeutics, and grants from Clovis, Genentech, AbbVie, Astra Zeneca, all outside the submitted work. R.E. O'Cearbhaill reports receiving honoraria/consulting/advisory role from GlaxoSmithKline, Fresenius, Seagen Inc., Carina Biotech and institutional research funding: Juno Therapeutics, Sellas Life Sciences, Ludwig Institute for Cancer Research, Stem CentRx, TapImmune Inc., TCR2 Therapeutics, Regeneron, Genmab, Atara Biotherapeutics, GlaxoSmithKline, AstraZeneca/Merck, Syndax, Genentech, Kite/Gilead, Gynecologic Oncology Group Foundation. Meal from AstraZeneca. B. Weigelt reports ad hoc membership of the scientific advisory board of Repare Therapeutics. The remaining authors have no conflicts of interest to declare. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Moukarzel Lea, A., et al. (2023). "Association of bowel preparation with surgical-site infection in gynecologic oncology surgery: Post-hoc analysis of a randomized controlled trial." Gynecologic Oncology 168: 100-106.
	Objective: To determine the relationship between bowel preparation and surgical-site infection (SSI) incidence following colorectal resection during gynecologic oncology surgery.; Methods: This post-hoc analysis used data from a randomized controlled trial of patients enrolled from 03/01/2016-08/20/2019 with presumed gynecologic malignancy investigating negative-pressure wound therapy among those requiring laparotomy. Patients were treated preoperatively without bowel preparation, oral antibiotic bowel preparation (OABP), or OABP plus mechanical bowel preparation (MBP) per surgeon preference. Univariate and multivariable analyses with stepwise model selection for SSI were performed for confirmed gynecologic malignancies requiring colorectal resection.; Results: Of 161 cases, 15 (9%) had no preparation, 39 (24%) OABP only, and 107 (66%) OABP+MBP. The overall SSI rate was 19% (n = 31)-53% (n = 8/15) in the no preparation, 21% (n = 8/39) in the OABP alone, and 14% (n = 15/107) in the OABP+MBP groups (P = 0.003). The difference between OABP and OABP+MBP was non-significant (P = 0.44). The median length of stay was 9 (range, 6-12), 6 (range, 5-8), and 7 days (range, 6-10), respectively (P = 0.045). The overall complication rate (34%; n = 54) did not significantly vary by preparation type (P = 0.23). On univariate logistic regression analysis, OABP (OR, 0.23; 95% CI: 0.06-0.80) and OABP+MBP (OR, 0.14; 95% CI: 0.04-0.45) were associated with decreased SSI risk compared to no preparation (P = 0.004). On multivariate analysis, both methods of preparation retained a significant impact on SSI rates (P = 0.004).; Conclusion: Bowel preparation is associated with reduced SSI incidence and is beneficial for patients undergoing gynecologic oncology surgery with anticipated colorectal resection. Further investigation is needed to determine whether OABP alone is sufficient.; Competing Interests: Declaration of Competing Interest Dr. Leitao reports personal fees from J&J/Ethicon and Takeda, and grants from KCI/Acelity. Dr. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. Dr. Abu-Rustum reports research funding paid to the institution by GRAIL. Dr. Jewel reports personal fees from Covidien/Medtronic. The other authors do not have potential conflicts of interest to declare. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mounir, D., et al. (2022). "Comparison of Vaginal Intraperitoneal and Extraperitoneal Uterosacral Ligament Suspensions for Post-Hysterectomy Vaginal Vault Prolapse: A Randomized Clinical Trial." International Urogynecology Journal 33(Supplement 2): S517-S518.
	Introduction: Uterosacral ligament suspension surgery is commonly utilized to correct post-hysterectomy vaginal vault prolapse (VVP). Vaginal intraperitoneal uterosacral vault suspension (IUSVS) is a viable option, but intraperitoneal access can be challenging. An alternative approach is an extraperitoneal uterosacral vault suspension (EUSVS) which has been shown in previous studies to have similar efficacy on cure. Avoiding peritoneal entry may also decrease operative time and complications, such as cystotomy. The aim of our study was to compare surgical operative times, as a surrogate marker for surgical complexity, of IUSVS and EUSVS in patients with post-hysterectomy VVP. Objective(s): The primary objective was to compare operative time between the two approaches. Secondary objectives were to compare hospital length of stay (LOS), estimated blood loss (EBL), perioperative complications, and short-term surgical success between the two groups. Method(s): A single-center, randomized, single-blind trial with the primary objective to compare operative time between vaginal IUSVS and EUSVS for post-hysterectomy VVP at our institution. Secondary outcomes included EBL, duration of hospitalization, short-term surgical success, and perioperative complications. Women were randomized 1:1 to IUSVS or EUSVS. Fisher's exact test or Chi-square test was used for discrete variables and Wilcoxon signed-rank test for continuous variables. Paired t-test was used to compare preoperative and postoperative patient-centered questionnaire scores. Result(s): 33 patients were enrolled and randomized. Groups had similar baseline characteristics. The proportion of preoperative POPQ stage 3 and 4 did differ significantly between the groups. Our primary outcome data of operative time in the ITT and PP analysis, which excluded 1 crossover patient, did not differ significantly between the groups. Median operative time difference was not statistically significant between the IUSVS [164 minutes (156, 173)] and EUSVS [144 minutes (132, 180)] (ITT p=0.072, PP p=0.074). Mid-urethral sling was the only observed concomitant procedure to differ significantly between the groups (IUSVS 0.00 % vs EUSVS 43.75%, p=0.26). Additionally, in the adjusted analysis, using a two-way ANOVA, we observed no significant effect on operative time when controlling for mid-urethral sling (p=0.1173). Secondary outcomes of EBL, hospital LOS, perioperative complications, patient centered questionnaire scores, and perioperative complications did not differ significantly between the groups. Conclusion(s): There was no significant difference in operative time between EUSVS and IUSVS for post-hysterectomy VVP. Additionally, there were no differences in EBL, hospital LOS, perioperative complications, and short-term surgical success related to the surgical approach. EUSVS is a viable alternative to IUSVS.

Mounir, D., et al. (2022). "COMPARISON OF VAGINAL INTRAPERITONEAL AND EXTRAPERITONEAL UTEROSACRAL LIGAMENT SUSPENSIONS FOR POST-HYSTERECTOMY VAGINALVAULT PROLAPSE: a RANDOMIZED CLINICAL TRIAL." Female Pelvic Medicine & Reconstructive Surgery 28(6): S283‐S284.
	Introduction: Uterosacral ligament suspension surgery is commonly utilized to correct post‐hysterectomy vaginal vault prolapse (VVP). Vaginal intraperitoneal uterosacral vault suspension (IUSVS) is a viable option, but intraperitoneal access can be challenging. An alternative approach is an extraperitoneal uterosacral vault suspension (EUSVS) which has been shown in previous studies to have similar efficacy on cure. Avoiding peritoneal entry may also decrease operative time and complications, such as cystotomy. The aim of our study was to compare surgical operative times, as a surrogate marker for surgical complexity, of IUSVS and EUSVS in patients with posthysterectomy VVP. Objective: The primary objective was to compare operative time between the two approaches. Secondary objectives were to compare hospital length of stay (LOS), estimated blood loss (EBL), perioperative complications, and shortterm surgical success between the two groups. Methods: A single‐center, randomized, single‐blind trial with the primary objective to compare operative time between vaginal IUSVS and EUSVS for posthysterectomy VVP at our institution. Secondary outcomes included EBL, duration of hospitalization, short‐term surgical success, and perioperative complications. Women were randomized 1:1 to IUSVS or EUSVS. Fisher's exact test or Chi‐square test was used for discrete variables and Wilcoxon signed‐rank test for continuous variables. Paired t‐test was used to compare preoperative and postoperative patient‐centered questionnaire scores. Results: 33 patients were enrolled and randomized. Groups had similar baseline characteristics. The proportion of preoperative POPQ stage 3 and 4 did differ significantly between the groups. Our primary outcome data of operative time in the ITT and PP analysis, which excluded 1 crossover patient, did not differ significantly between the groups. Median operative time difference was not statistically significant between the IUSVS [164 minutes (156, 173)] and EUSVS [144 minutes (132, 180)] (ITT P = 0.072, PP P = 0.074). Midurethral sling was the only observed concomitant procedure to differ significantly between the groups (IUSVS 0.00 % vs EUSVS 43.75%, P = 0.26). Additionally, in the adjusted analysis, using a two‐way ANOVA, we observed no significant effect on operative time when controlling for mid‐urethral sling (P = 0.1173). Secondary outcomes of EBL, hospital LOS, perioperative complications, patient centered questionnaire scores, and perioperative complications did not differ significantly between the groups. Conclusions: There was no significant difference in operative time between EUSVS and IUSVS for post‐hysterectomy VVP. Additionally, there were no differences in EBL, hospital LOS, perioperative complications, and short‐term surgical success related to the surgical approach. EUSVS is a viable alternative to IUSVS.

Mourad, A., et al. (2021). "Evidence-based clinical prioritization of embryos with mosaic results: a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics 38(11): 2849-2860.
	Purpose: The purpose of this review and meta-analysis is to standardize the practice of mosaic embryo transfer, based on the current available evidence.; Methods: This is a systematic review and meta-analysis. Relevant studies published were comprehensively selected using PubMed, Medline, Embase, and CENTRAL until 5 March 2021. Prospective and retrospective studies reporting the genetic analysis and clinical outcomes of mosaic embryo transfer were included. Risk of bias assessment was based on the Newcastle-Ottawa scale for the non-randomized studies. The primary and secondary outcomes were combined ongoing pregnancy and live birth rate and miscarriage rate, respectively.; Results: There were no differences between low and high mosaic embryos when a cut-off of 40% was used in terms of OP/LBR and SAB. However, low mosaics with a cut-off of 50% compared to high mosaics showed a significantly higher OP/LBR in the NGS but not in the a-CGH group, and a significantly lower risk of SAB. No differences were noted between mosaic monosomies versus trisomies and single versus double mosaics for both OP/LBR and SAB. Finally, segmental mosaics showed a higher OP/LBR and a lower SAB compared to whole chromosomes, and single and double mosaics had a higher OP/LBR compared to complex mosaics.; Conclusions: A cut-off of 50% in defining low versus high mosaic embryos is preferable to a threshold of 40% when using NGS platform. No priority was established for mosaic trisomies over monosomies. Single and double mosaics must be preferred over complex mosaics and segmental mosaics must be preferred over whole chromosome mosaics. These results should be interpreted in the context of specific chromosomes involved in the mosaicism. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mourksi, N.-E.-H., et al. (2023). "Ribosome biogenesis-based predictive biomarkers in endocrine therapy (Anastrozole) combined with mTOR inhibitor (Vistusertib) in endometrial cancer: translational study from the VICTORIA trial in collaboration with the GINECO group." Molecular Oncology 17(1): 27-36.
	Resistance of advanced hormone-dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of Vistusertib (V, mTOR inhibitor) and Anastrozole (A, aromatase inhibitor) improves the progression-free rate compared to Anastrozole alone. However, a better patient selection based on biomarkers would improve patient outcome. We evaluate for the first time the usage of ribosome biogenesis (RiBi) factors as a source of innovative markers. Using 47 FFPE tumours (A n = 18; V + A n = 29), 32 blood samples (A n = 13; V + A n = 19) and 30 samples of total RNAs (A n = 12; V + A n = 18) from the VICTORIA clinical trial, we observed an association between RiBi-associated markers and drug activity or prediction of treatment response. NOP10 and NHP2 mRNA levels were significantly higher in non-responders compared to responders in the Vistusertib + Anastrozole arm (P = 0.0194 and P = 0.0002 respectively; i.e. 8 weeks progression-free survival as endpoint). This study provides RiBi-based markers relevant for a better selection of patients with advanced endometrial carcinoma by predicting the response of endocrine therapy combined with mTOR inhibitor. (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Mourtada, F., et al. (2023). "Multi-Center Investigation of Inter-Observer Variability of a Novel Mobile CBCT Ring for Gynecological Cancer HDR Brachytherapy." Brachytherapy 22(5 Supplement): S79.
	Purpose: A novel mobile cone-beam computed tomography (CBCT) imaging device (Elekta Inc.) aims to improve efficiency with on-demand imaging in the HDR vault during and after applicator insertion. We evaluated whether inter-observer contour variability of standard organs-at-risk (OARs) was similar using this novel CBCT (Ring-CBCT) as compared to diagnostic-quality simulation CT (CT-Sim) for cervical cancer HDR brachytherapy. Material(s) and Method(s): A patient with stage IIB cervical cancer was implanted with the CT/MR Venezia Tandem (6-cm, 30-deg) with 26-mm dia. Lunar Ovoids. Images were acquired with Ring-CBCT (Elekta ImagingRing v 2.5.2) using 120 kVp, 8 mA, and 0.6x0.6x1.2 mm voxel size, and CT-Sim (Siemens SOMATOM go.Open Pro) using department standard pelvis imaging protocol (120 kVp, 1.17x1.17x1 mm voxel size, 0.8 pitch). Zypher transfer system (Orfit Inc.) was used to move patient to reduce applicator motion. Bladder, rectum, sigmoid, and lower bowel were independently contoured by 11 brachytherapists on Ring-CBCT and CT-Sim in Oncentra TPS. After each session, the physician answered a survey with a score from 1-10 for a qualitative evaluation of their comfort level for each contour. Inter-observer contour variability was quantitatively evaluated using Average Surface Distance, 95% Housdorff Distance, 100% Housdorff Distance, Surface Overlap, Surface Dice, and Volumetric Dice comparisons between a reference contour (RA) and each physician's contour. Wilcoxon signed-rank test was applied to test the statistical difference between the metrics on CT-sim and Ring-CBCT. Result(s): Eleven physicians completed all four OAR contours on both imaging modalities and completed all surveys. The questionnaire results revealed there was greater confidence in the CT contours when compared to the Ring-CBCT contours. Comfort levels were a median of 10 (9-10) vs. 8 (6-10 (p<0.01) for bladder, 9 (8-10) vs. 8 (4-10) (p<0.01) for rectum, 8.5 (8-10) vs. 6.5 (2-10) (p<0.001) for sigmoid and 8 (7-10) vs. 5 (1-10) (p<0.001) for bowel, respectively. Inter-observer variations in OAR delineation on CT-sim and Ring CBCT are shown in Table 1. Overall, CT-sim showed lower interobserver variation when compared to the Ring-CBCT. There were no statistically significant differences between contour variability with Ring-CBCT when compared to contour variability assessed with CT-sim for most OARs and metrics evaluated. Bladder showed the most prevalent statistically significant variability differences between CT-Sim and Ring-CBCT as evaluated by surface metrics (Average Surface Distance and Hausdorff Distance). Conclusion(s): Using a multi-center approach and a comprehensive suite of comparison metrics, this study provides the first report of image quality assessment of a novel Ring CBCT for HDR applications. Our data show that for the presented patient, the contours generated using the Ring-CBCT show similar variability when compared to contours generated using standard of care CT-Sim imaging. Based on the physician survey however, OARs contouring confidence with CT-Sim is higher than Ring-CBCT. This study provides a framework for future studies of CBCT imaging for OARs delineation and treatment planning for gynecological cancer brachytherapy.Copyright © 2023

Mousa, G. S., et al. (2021). "Effect of low level laser on pelvic floor muscles and fascia in cases of stress urinary incontinence: a randomized controlled trial." Physiotherapy quarterly 29(4): 22‐27.
	Introduction. The aim of the study was to determine the effect of low level laser applied for 3 months, 2 sessions per week, on pelvic floor muscles and fascia compared with a pelvic floor exercise program in patients with stress urinary incontinence. Methods. The randomized controlled trial involved 30 patients with stress urinary incontinence and with pelvic floor muscle strength not less than grade 1 on the oxford scale. They were assigned to 2 equal groups. The experimental group received low level laser for 15 minutes and a pelvic floor muscle exercise program for 30 minutes, 2 sessions per week, for 12 weeks; the control group only received the pelvic floor muscle exercise program for 30 minutes, 2 sessions per week, for 12 weeks. The pelvic floor muscles were evaluated before and after treatment with a Neen Peritone perineometer and the Modified oxford Grading Scale. The Revised Urinary incontinence Scale served to assess incontinence severity before and after treatment. Results. The statistical analysis indicated a significant increase in pelvic floor muscle strength (p < 0.05), a significant improvement of the grade muscle test of pelvic floor muscles (p < 0.05), and a significant reduction of Revised Urinary incontinence Scale score (p < 0.05) after treatment compared with pre‐treatment status in both groups. Also, there was a significant improvement in all dependent variables in favour of the experimental group. Conclusions. Low level laser may be an effective intervention in treating stress urinary incontinence and improving pelvic floor muscle strength and fascia.

Mousavi, R., et al. (2022). "Effects of Melatonin and/or Magnesium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial." Biological trace element research 200(3): 1010-1019.
	Magnesium and melatonin are known to exert multiple beneficial effects including anti-inflammatory and antioxidant actions. This study was designed to determine the effects of magnesium and/or melatonin supplementation on metabolic profiles in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted among 84 subjects with PCOS aged 18-40 years old. Patients were randomly assigned based on the random block procedure to take magnesium, melatonin, magnesium plus melatonin, or placebo for 8 weeks. Fasting blood samples were taken at baseline and after the intervention to quantify related variables. After the 8-week intervention, an insignificant marginal difference was seen in waist circumference (WC) between groups (P = 0.085). Magnesium-melatonin co-supplementation resulted in more reductions in hirsutism compared with other groups (P < 0.001). Serum levels of tumor necrosis factor-α (TNF-α) declined significantly in the melatonin and co-supplementation groups compared to baseline (P < 0.05). Also, magnesium plus melatonin was associated with a more increase in total antioxidant capacity (TAC) levels, as compared to the other treatment groups (P = 0.001). Overall, we found a favorable effect of co-supplementation of magnesium and melatonin for 8 weeks in women with PCOS on hirsutism, serum TNF-α, and TAC levels. Furthermore, melatonin independently contributed to decreased serum values of TNF-α.Clinical trial registration number http://www.irct.ir : IRCT20191130045556N1, January 2020. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Moustafa Ahmed, A., et al. (2020). "Depression Following Major Life Transitions in Women: A Review and Theory." Psychological reports 123(5): 1501-1517.
	Depression can occur due to common major life transitions, such as giving birth, menopause, retirement, empty-nest transition, and midlife crisis. Although some of these transitions are perceived as positive (e.g., giving birth), they may still lead to depression. We conducted a systematic literature review of the factors underlying the occurrence of depression following major life transition in some individuals. This review shows that major common life transitions can cause depression if they are sudden, major, and lead to loss (or change) of life roles (e.g., no longer doing motherly or fatherly chores after children leave family home). Accordingly, we provide a theoretical framework that explains depression caused by transitions in women. One of the most potential therapeutic methods of ameliorating depression associated with life transitions is either helping individuals accept their new roles (e.g., accepting new role as a mother to ameliorate postpartum depression symptoms) or providing them with novel life roles (e.g., volunteering after retirement or children leave family home) may help them overcome their illness.

Moustafa, M. H., et al. (2021). "Letrozole Pretreatment With Misoprostol Versus Misoprostol Alone For Induction of First Trimesteric Missed Miscarriage A Randomized Controlled Trial." QJM : monthly journal of the Association of Physicians 114(SUPPL 1).
	Background Miscarriage or spontaneous abortion is the involuntary termination of pregnancy before 20 weeks of gestation or a fetus born weighting less than 500 grams. Objective To compare between the safety and efficacy of two treatment modalities in medical termination of first trimesteric missed miscarriage. Patients and Methods This study was conducted at outpatient Obstetric clinic of Ain Shams maternity hospital in the period between June 2017 and December 2018. The patients who were fulfilling the inclusion criteria, were recruited in the study, then an informed consent was taken before starting the trial. Results In the total of 88 patients who were recruited in the study, 3 patients dropped from the study, 2 patients from the first group and 1 patient from the second group, so 85 patients were analyzed, the complete abortion rate of the letrozole group was significantly higher than that of the misoprostol only group (83.72% compared to 64.29%). Conclusion The use of letrozole pretreatment followed by misoprostol for induction of abortion in the first trimester is associated with higher complete abortion rate than misoprostol only.

Moustafa, S., et al. (2021). "Patient and provider satisfaction with saline ultrasound versus office hysteroscopy for uterine cavity evaluation prior to in vitro fertilization: a randomized controlled trial." Journal of Assisted Reproduction and Genetics 38(3): 627‐634.
	Purpose: To compare patient and provider satisfaction with saline ultrasound (SIS) versus office hysteroscopy for cavity evaluation prior to in vitro fertilization (IVF) and to assess the capability of hysteroscopy to manage pathology at time of diagnosis to reduce delays and supernumerary procedures. Methods: This was a randomized, controlled trial in a university fertility clinic. One hundred enrolled subjects undergoing routine uterine cavity evaluation prior to planned embryo transfer were randomized to SIS or office hysteroscopy without anesthesia. Subjects and providers completed surveys about their experience. Subjects with findings on SIS had a hysteroscopy performed or scheduled for further evaluation. Those with hysteroscopy findings had management attempted within the same procedure. Results: Overall patient satisfaction was high and did not differ between groups, while providers indicated that hysteroscopy provided a better cavity evaluation. There was no difference in time to complete procedures between groups. Pain score on a ten‐scale was slightly higher in the hysteroscopy group compared to the SIS group (3.38 ± 1.85 vs. 2.44 ± 1.64, p < 0.01), but this did not impact satisfaction scores. Although pathology was found in a similar rate (22% vs. 36% for SIS and HSC groups, respectively), those in the SIS group all required secondary procedures, while only 1/17 did in the HSC group (p < 0.01). Conclusion: Although the hysteroscopy group exhibited slightly higher pain scores, overall patient and provider satisfaction was high and similar between groups. There were significantly fewer secondary procedures and delays in the hysteroscopy group. Hysteroscopy is a reasonable first line screening tool for patients requiring cavity evaluation. Trial registration: ClinicalTrials.gov, NCT04415489.

Ms and D. Friend (2022). "Systemic and Local Pharmacokinetics of DARE-BV1, a Novel Single Dose 2% Clindamycin Phosphate Vaginal Gel for the Treatment of Bacterial Vaginosis." American Journal of Obstetrics and Gynecology 226(2): 291.
	Objectives: DARE-BV1 is a novel, highly viscous single dose 2% clindamycin phosphate vaginal gel being investigated as a new treatment for bacterial vaginosis. In a recently completed large, randomized multi-center, placebo-controlled study, DARE-BV1 demonstrated a clinical cure of 70.5% vs. 35.6% in the placebo group (p < 0.001) at Days 21-30. The objective of this study was to determine the systemic and vaginal pharmacokinetics (PK) of DARE-BV1. Method(s): Twenty-one (21) healthy adult women volunteers were recruited at a single site (ICON Early Phase Services, San Antonio, TX, USA). One subject terminated early due to potential COVID-19 exposure. At the Screening Visit, past medical and gynecological histories were collected/evaluated. Additionally, the following samples/tests were performed and collected: Affirm Vaginal Pathogens DNA Direct Probe test (VAGDNA) for Candida species, Gardnerella vaginalis, and Trichomonas vaginalis, tests for gonorrhea and chlamydia, human papillomavirus (HPV) test. Study drug (5 g of 2% clindamycin phosphate vaginal gel, 100 mg clindamycin) was applied intravaginally on Day 1 at the study clinic. Subjects had blood draws for plasma clindamycin concentrations taken at 0 hours (pre-dose) and then at 2, 4, 6, and 8 hours (+/-15 minutes) post-dose on Day 1 and at 24, 48, 72, 96, 120, and 144 hours (+/-2 hours) post-dose (Days 2 through 7). In addition, samples for vaginal clindamycin phosphate concentrations were collected once daily on Days 1 through 7 (with the Day 1 sampling done pre-dose). Plasma concentrations of clindamycin were assessed using a validated LC-MS/MS method with a lower limit of quantitation (LOQ) of 0.5 ng/mL. The concentration of clindamycin phosphate from vaginal swabs was measured by extracting the swabs followed by HPLC analysis. The LOQ for this method was 2.8 mug/g. Result(s): The plasma PK parameters collected are shown in Table 1. The Cmax and AUClast values are somewhat higher than those observed following a single or multiple doses of vaginal Cleocin, a currently approved clindamycin-based product for the treatment of bacterial vaginosis. They are also higher than those observed following vaginal administration of Clindesse, another clindamycin-based product approved for the treatment of bacterial vaginosis. Tlast measured is consistent with a prolonged release of clindamycin phosphate from the gel. Vaginal concentrations of clindamycin phosphate are shown for all 21 subjects in Figure 1. Conclusion(s): The plasma PK data as well as the vaginal clindamycin phosphate concentrations over time suggest that properties of DARE-BV1 maintain the drug at the site of action as compared to the other clindamycin-based products, maximizing the overall efficacy of the product for the treatment of BV. These findings may account for the relatively high efficacy of DARE-BV1 compared with other vaginal products used to treat BV. [Formula presented]Copyright © 2021

Mu, F., et al. (2023). "Pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus low molecular-weight heparin: A meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 287: 29-35.
	Objective: Current opinion on the superiority of fondaparinux versus low molecular-weight heparin (LMWH) in treating recurrent miscarriage is controversial. This meta-analysis aimed to comprehensively compare the pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus LMWH.; Methods: EMBASE, PubMed, Cochrane, China National Knowledge Internet (CNKI), Wanfang Database, and China Science and Technology Journal Database (CQVIP) databases were searched for articles reporting fondaparinux versus LMWH in treating recurrent miscarriage till June 10, 2022. Inclusion criteria for study screening were: (i) randomized, controlled trials (RCT), non-randomized controlled studies, or observational studies; (ii) patients aged over 18 years; (iii) patients with recurrent miscarriage during gestation period; (iv) patients in the experimental/observational group who received FD, and patients in the control group who received LMWH; (v) studies involving at least one outcome of interest for the current analysis. Exclusion criteria were: (i) systematic reviews, meta-analyses, case reports, or animal studies; (ii) duplicated studies; (iii) incomplete or inconsistent data. Quality assessment was conducted with Newcastle-Ottawa Scale criteria or Cochrane Collaboration. Data of live birth, abortion, birth weight, fetal growth restriction (FGR), and adverse events were extracted and synthesized.; Results: Six eligible studies (4 observational studies and 2 RCTs) with 321 patients receiving fondaparinux and 546 patients receiving LMWH were enrolled. Live birth (relative risks (RR) = 1.05, 95% confidence interval (CI) = 0.97 ∼ 1.14, P = 0.217), abortion (RR = 0.73, 95% CI = 0.50 ∼ 1.08, P = 0.113), birth weight (weighted mean difference = 167.20, 95% CI = -236.89 ∼ 571.30, P = 0.417), and FGR (RR = 0.95, 95% CI = 0.25 ∼ 3.59, P = 0.942) were of no difference between patients receiving fondaparinux and LMWH. Regarding adverse events, the incidence of ecchymosis (RR = 0.11, 95% CI = 0.03 ∼ 0.46, P = 0.002) and skin reaction at injection site (RR = 0.15 95% CI = 0.05 ∼ 0.44, P = 0.001) were lower in patients receiving fondaparinux compared with those receiving LMWH, while that of thrombocytopenia (RR = 0.45, 95% CI = 0.09 ∼ 2.14, P = 0.315), vagina bleeding (RR = 1.03, 95% CI = 0.62 ∼ 1.71, P = 0.646), and oral mucosa hemorrhage (RR = 1.08, 95% CI = 0.33 ∼ 3.51, P = 0.899) did not vary between these patients receiving these two treatments. However, most studies were conducted in China, which could induce regional and ethnic bias.; Conclusion: Fondaparinux is attributable to fewer adverse events and similar pregnancy outcomes compared with LMWH in patients with recurrent miscarriage.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Muaddi, H., et al. (2021). "Clinical Outcomes of Robotic Surgery Compared to Conventional Surgical Approaches (Laparoscopic or Open): A Systematic Overview of Reviews." Annals of surgery 273(3): 467-473.
	Objective: Describe clinical outcomes (eg, postoperative complications, survival) after robotic surgery compared to open or laparoscopic surgery.; Background: Robotic surgery utilization has increased over the years across a wide range of surgical procedures. However, evidence supporting improved clinical outcomes after robotic surgery is limited.; Methods: We systematically searched MEDLINE, EMBASE, and the Cochrane Central Register of systematic reviews from inception to January 2019 for systematic reviews describing postoperative outcomes after robotic surgery. We qualitatively described patient outcomes of commonly performed robotic procedures: radical prostatectomy, hysterectomy, lobectomy, thymectomy, rectal resection, partial nephrectomy, distal gastrectomy, Roux-en-Y gastric bypass, hepatectomy, distal pancreatectomy, and cholecystectomy.; Results: One hundred fifty-four systematic reviews included 336 studies and 18 randomized controlled trials reporting on patient outcomes after robotic compared to laparoscopic or open procedures. Data from the randomized controlled trials demonstrate that robotic-assisted radical prostatectomy offered fewer biochemical recurrence and improvement in quality of recovery and pain scores only up to 6 weeks postoperatively compared to open radical prostatectomy. When compared to laparoscopic prostatectomy, robotic surgery offered improved urinary and sexual functions. Robotic surgery for endometrial cancer had fewer conversion to open compared to laparoscopic. Otherwise, robotic surgery outcomes were similar to conventional surgical approaches for other procedures except for radical hysterectomy where minimally invasive approaches may result in patient harm compared to open approach.; Conclusion: Robotic surgery has been widely incorporated into practise despite limited supporting evidence. More rigorous research focused on patient-important benefits is needed before further expansion of robotic surgery.; Competing Interests: The authors report no conflicts of interest. (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Muaibati, M., et al. (2023). "Efficacy of immune checkpoint inhibitor monotherapy or combined with other small molecule-targeted agents in ovarian cancer." Expert Reviews in Molecular Medicine 25: e6.
	Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

Muallem Mustafa, Z., et al. (2022). "A Promising Approach for Primary Cytoreductive Surgery for Advanced Ovarian Cancer: Survival Outcomes and Step-by-Step Description of Total Retroperitoneal en-Bloc Resection of Multivisceral-Peritoneal Packet (TROMP)." Journal of Personalized Medicine 12(6).
	(1) Background: A complete tumor resection during primary cytoreductive surgery has been reported to be the most important and perhaps the only independent prognostic factor in advanced ovarian cancers. The goal of complete cytoreduction needs to be weighed against the potential morbidities and long-term survival outcomes. (2) Methods: in this retrospective analysis of a prospectively obtained database, 208 consecutive patients with advanced ovarian cancer who underwent a conventional primary cytoreductive surgery (150 patients) or TROMP technique (58 patients) were included. Progression-free and overall survival rates were calculated using Kaplan-Meier analysis as well as the 95% confidence interval of the hazard ratio between treatment groups. (3) Results: After a median follow-up phase of more than 3 years (range 1-72 months), there are no statistically significant differences between both groups in progression-free and overall survival rates. Albeit, the TROMP group included statistically significant more advanced-stage cases compared to the conventional surgery group. (4) Conclusions: the TROMP technique is a promising tool for successful primary cytoreductive surgery in a selected group of patients with high tumor burdens in order to achieve optimal surgical results and survival outcomes without introducing any additional risks or complications.

Muallem Mustafa, Z., et al. (2022). "Reconstructive Surgery versus Primary Closure following Vulvar Cancer Excision: A Wide Single-Center Experience." Cancers 14(7).
	(1) Background: plastic reconstruction in vulvar surgery can lead to a better treatment outcome than primary closure. This study aims to compare the preoperative parameters (co-morbidities and tumor size) and postoperative results (tumor free margins and wound healing) between the primary closure and reconstructive surgery after vulvar cancer surgery; (2) Methods: this is a retrospective analysis of prospectively collected data from 2009 to 2021 at a tertiary cancer institution; (3) Results: 177 patients were included in the final analysis (51 patients had primary closure PC and 126 had reconstructive surgery RS). About half (49%) of the PC patients had no co-morbidities ( p = 0.043). The RS group had a 45 mm median maximal tumor diameter compared to the PC group's 23 mm ( p = 0.013). More than 90% of RS and 80% of PC had tumor-free margins ( p = 0.1). Both groups had anterior vulvar excision as the most common surgery (52.4% RS vs. 23.5% PC; p = 0.001). Both groups had identical rates of wound healing disorders. In a median follow-up of 39 months; recurrent disease was found in 23.5% of PC vs. 10.3% in RS ( p = 0.012). In terms of overall survival there was no significant difference between the both groups; (4) Conclusions: reconstructive vulvar surgery enables enhanced complete resection rates of larger vulvar tumors with better anatomical restoration and a comparable wound recovery in comparison to primary closure. This results in a lower recurrence rate despite the increased tumor volume.

Muangwong, P., et al. (2022). "Brachytherapy dose changes: comparing in-room and out-room image-guided brachytherapy. A randomized study." Journal of Contemporary Brachytherapy 14(4): 347-353.
	Purpose: Image-based brachytherapy, involving an image machine and a brachytherapy unit in the same room (in-room brachytherapy [IRBT]), limits patient movements; however, this technique may not be feasible in high workload centers. In this study, we compared changes in the dose and volume of organs at risk (OARs) with out-room brachytherapy (ORBT) technique, in which patients musted be transferred to a waiting room and then transferred back for brachytherapy delivery. Material(s) and Method(s): This was a randomized prospective study comparing changes in D2cc doses and volume of OARs during IRBT and ORBT. Patients underwent CT for treatment planning (CT1) installed in brachytherapy loading room, and another CT immediately before brachytherapy (CT2) during each fraction. While patients remained on CT table after CT1 during treatment planning and delivery in IRBT arm, they were transferred out to waiting room and back to CT table in ORBT arm. CT2 was analyzed with CT1 to evaluate any changes in volumes and doses. Result(s): A total of 294 fractions of brachytherapy were considered. The findings indicated no significant differences in the mean D2cc changes (Gy) (CT2 minus CT1) to the bladder, rectum, and sigmoid between IRBT and ORBT (mean +/-SD: -0.07 +/-0.36 vs. -0.01 +/-0.39, p = 0.1426; -0.15 +/-0.32 vs. -0.14 +/-0.29, p = 0.8898; -0.17 +/-0.38 vs. -0.19 +/-0.31, p = 0.5221, respectively). Moreover, significant correlations were observed between D2cc changes and volume changes to each of OARs, p < 0.001. Conclusion(s): IRBT does not result in differences in dose changes between planning and pre-treatment imaging when compared with ORBT. Consequently, ORBT can be considered for routine practice in high workload centers. Correlations in volume change and dose change to OARs were also observed. Copyright © 2022 Termedia Publishing House Ltd.. All rights reserved.

Mueller, E. R., et al. (2023). "Nocturnal polyuria in women: results from the EpiNP study." International Urogynecology Journal 34(8): 1743-1751.
	Introduction and hypothesis: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). Method(s): Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting >=2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). Result(s): A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported >=2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes >=2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. Conclusion(s): NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.Copyright © 2023, The International Urogynecological Association.

Mueller, M. G., et al. (2021). "Restricted Convalescence Following Urogynecologic Procedures: 1-Year Outcomes From a Randomized Controlled Study." Female Pelvic Medicine & Reconstructive Surgery 27(2): e336‐e341.
	OBJECTIVE: To assess the relationship between postoperative activity recommendations and satisfaction and anatomic and functional outcomes 1 year after surgery for symptomatic prolapse. METHODS: This is a planned secondary analysis reporting 1‐year functional and anatomic outcomes of a multicenter, randomized, double‐masked clinical trial "ReCOUP." In the original trial, women undergoing surgery for prolapse were randomized to liberal (no limitations on physical activity) or restricted (heavy lifting and high‐impact activity prohibited) postoperative activity recommendations for 3 months after surgery. At 1 year, our primary outcome was satisfaction, assessed using a 5‐point Likert scale answer to the question, "How satisfied are you with the result of your prolapse surgery?" Anatomic surgical failure was met if women had prolapse beyond the hymen, apical descent greater than one third the vaginal length, OR retreatment for prolapse. RESULTS: Of the 95 women (n = 45 liberal, n = 50 restricted) who were randomized and completed primary 3‐month outcomes, 83 (87%) completed a functional assessment, and 77 (81%) completed both functional and anatomic assessment at 1 year. Satisfaction with surgery remained high (91.5%) with no differences between groups (86.8% vs 95.6% P = 0.155) as did anatomic and functional outcomes. There were 7.8% women who met criteria for anatomic surgical failure with no difference between the restricted (7.0%) and liberal group (8.8%). Three women (2 in the restricted group, 1 in the liberal group) with recurrent prolapse and underwent surgery. CONCLUSIONS: There were no significant differences in anatomic and functional outcomes at 12 months after surgery in women who resume postoperative activity liberally and those who restrict postoperative activity.

Mueller, M. G., et al. (2023). "Longitudinal urinary microbiome characteristics in women with urgency urinary incontinence undergoing sacral neuromodulation." International Urogynecology Journal 34(2): 517-525.
	Introduction and hypothesis: The objective was to evaluate the stability of the urinary microbiome communities in women undergoing sacral neuromodulation (SNM) for urgency urinary incontinence (UUI). We hypothesized that clinical response to SNM therapy would be associated with changes in the urinary microbiome. Method(s): Women completed the Overactive Bladder Questionnaire Short-Form, the International Consultation on Incontinence Questionnaire Short Form, and the Female Sexual Function Index at baseline and 3 months post-SNM implantation. Transurethral urinary specimens were obtained for microbiome analysis at baseline and 3 months postoperatively. The V4 region of the 16S rRNA gene (515F-806R) was amplified with region-specific primers, and Amplicon Sequence Variants (ASVs) were identified with a closed-reference approach of taxonomic classification. Alpha-diversity was calculated using the phylogenetic (i.e., Faith's phylogenetic diversity) and nonphylogenetic metrics (i.e., Shannon diversity, and Pielou's evenness) using the QIIME2 plugin. Longitudinal paired volatility analysis was performed using the DEICODE and Gemelli plugin to account for host specificity across both time and space. Result(s): Nineteen women who underwent SNM and provided both baseline and 3-month urine samples were included in this analysis. Women reported improvement in objective (number of UUI episodes) and subjective (symptom severity and health-related quality of life) measures. Ninety percent of the bacteria were classified as Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. No significant differences were observed in each subject's beta-diversity at 3 months compared with their baseline microbiome. Conclusion(s): Our descriptive pilot study of a cohort of women who had achieved objective and subjective improvements in UUI following SNM therapy demonstrates that the urinary microbiome remains relatively stable, despite variability amongst the cohort.Copyright © 2022, The International Urogynecological Association.

Muenster University, H. (2022). Influence of an App on Quality of Life of Women With Endometriosis.
	No Results Available Behavioral: use of Endo App® quality of life of endometriosis patients Female Not Applicable 106 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Pre ELEA January 30, 2022

Muenster University, H. and H. E. H. Gmb (2023). Impact on Quality of Life of "Endo-App" (ELEA).
	No Results Available Device: Use of Endo App EHP 5|FSS survey|FESS survey|PDI survey|DASS-21 survey Female Not Applicable 300 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ELEA September 1, 2023

Mufti Amna, F., et al. (2023). "Women Suffering From Endometrioma-Related Symptoms May Benefit From Silymarin, An Antioxidant." JPMA. The Journal of the Pakistan Medical Association 73(11): 2323.
	
Mughal Muhammad, K., et al. (2023). "Trajectories of maternal depressive symptoms from pregnancy to 11 years postpartum: Findings from Avon Longitudinal Study of Parents and Children (ALSPAC) cohort." Journal of Affective Disorders 328: 191-199.
	Background: Maternal depressive symptoms are common in pregnancy and may extend to the perinatal period and beyond for some women. To date, few longitudinal studies have investigated maternal depressive symptoms from pregnancy to eleven years postpartum. Drawing data from a large population-based study cohort the aims of this study were to 1) identify distinct groups of mothers defined by their trajectories of depressive symptoms spanning from pregnancy to eleven years following the birth of the child, and 2) to identify psychosocial risk factors during pregnancy and in the first few postnatal years that are associated with these trajectories.; Methods: Data were analyzed from 14,170 mothers who participated in Avon Longitudinal Study of Parents and Children (ALSPAC). The Edinburgh Postnatal Depression Scale (EPDS) was used to capture maternal depressive symptoms across 10 time points including two prenatal (18 and 32 weeks), and eight postnatal (2, 8, 21, 33, 61, 73, 97 and 134 months) time points. The latent growth model was created to describe the course of maternal depressive symptoms across the preceding time points followed by a latent growth mixture modelling (LGMM) to identify distinct trajectories of depressive symptoms over time within the overall sample. The predictors of maternal depressive symptoms trajectories were categorized into sociodemographic, child, and psychosocial factors. The multinomial regression analyses were conducted to explore associations between the risk factors and depressive symptoms trajectories.; Results: LGMM identified four distinct trajectories of maternal depressive symptoms over time: minimal symptoms, increasing symptoms, persistent symptoms, and decreasing symptoms. Predictors of all patterns of depression - persistent, increasing and decreasing symptoms include smoking during pregnancy, and partner conflict. The strongest predictors of the persistent symptom trajectory included maternal history of depression and inadequate social support.; Limitations: The use of self-reported maternal mental health symptoms and under representation of ethnic minorities are our study's limitations.; Conclusions: The study findings highlight the importance of early identification and treatment for mothers experiencing depressive symptoms from pregnancy to the perinatal period and beyond.; Competing Interests: Conflict of interest None of the authors have any financial interest or benefit arising from the direct applications of this research study. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Muhanmode, Y., et al. (2022). "Curcumin and resveratrol inhibit chemoresistance in cisplatin-resistant epithelial ovarian cancer cells via targeting P13K pathway." Human & experimental toxicology 41: 9603271221095929.
	Background: The activation of the PI3K/AKT/mTOR pathway has been proved to be associated with survival as well as proliferation of various tumour cells in multiple cancer types, including epithelial ovarian cancer (EOC).; Purpose: Moreover, the activation of the PI3K/AKT/mTOR pathway is the key mechanism responsible for higher invasiveness and migratory capacities of ovarian cancer cells. Furthermore, PI3K is crucial for activation of the PI3K/AKT/mTOR pathway; therefore, its inhibition might be an effective strategy against cancer.; Research Design: The combination approach is now an established strategy against cancer. So, the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol along with cisplatin treatment on inhibition of the PI3K pathway in ovarian cancer cells.; Results: The present study confirmed significant inhibition of the PI3K/AKT/mTOR pathway as observed by Matrigel invasion assay, Western blot expression of important molecular markers and apoptotic markers.; Conclusion: The present study concludes that the combination of curcumin and resveratrol significantly sensitized the EOC cells to cisplatin treatment, thereby inhibiting chemoresistance in ovarian cancer cells by significant inhibition of the PI3K/AKT/mTOR pathway.

Muinos, F., et al. (2023). "Efficacy of a 0.005% estriol vaginal gel in preventing recurrent urinary tract infections in postmenopausal women with vaginal atrophy. Blissure study." Maturitas 173: 97.
	Background: Decreased estrogen levels after menopause result in vaginal atrophy, leading to elevated pH, lower levels of Lactobacilli and dysbiosis, increasing the frequency of Urinary Tract Infections (UTIs). Topical estrogens restore the atrophic vagina stimulating the proliferation of a balanced flora and preventing urinary symptoms. This preventive approach can be considered an alternative to the use of long-term antibiotics. Objective(s): This randomized, double-blind, placebo-controlled study assessed the efficacy of an ultra-low dose 0.005% estriol vaginal gel in preventing urinary tract infections in postmenopausal women presenting vaginal atrophy and recurrent urinary tract infections. Effect on asymptomatic bacteriuria, urinary symptoms and signs, vaginal pH, safety and acceptability were also evaluated. Method(s): Two groups of postmenopausal women (aged 45-80) with vaginal dryness and history of recurrent UTIs (>= 2 in 6 months or >=3 in 12 months) that received either 0.005% estriol vaginal gel or a placebo moisturising vaginal gel (daily for three weeks and twice weekly up to 24 weeks) were included. Data were collected at baseline, 3, 6, 12, 18 and 24-week visits. Result(s): 108 women were randomized (53 estriol/55 placebo). After treatment, all women receiving estriol presented a decrease in the frequency of UTIs. The incidence rate of UTIs (new cases per 100 women-year) resulted 26% lower in the group that received estriol vs the group that received placebo (32.34 vs 43.76 (RR=0.74) p<0.001). The incidence rate of asymptomatic bacteriuria was also significantly reduced (p=0.0469). There was a tendency to less urinary frequency, vaginal discharge, and urgency in the estriol group. PH value significantly improved in active group in all visits vs baseline. 90.9% of the women receiving estriol showed excellent/very good acceptability being the percentage of 100% therapeutic compliance throughout the study statistically higher in the estriol group (41.2% vs. 16.0%, p<0.005). Conclusion(s): Ultra-low dose 0.005% estriol vaginal gel in postmenopausal women with vaginal atrophy and history of recurrent UTIs, demonstrated a significantly lower incidence rate of UTIs and a significant decrease in vaginal pH compared to placebo. The difference in treatment compliance within the groups may be related to the clinical benefit perceived by women receiving estriol. 0.005% estriol vaginal gel as a treatment for the prevention of UTIs is a safe and well-accepted option. Declaration of competing interest Pharmaceutical Industry employeeCopyright © 2023

Mukhlef, I. I., et al. (2022). "The effect of vitamin D, zinc and metformin on poly cystic ovarian syndrome." NeuroQuantology 20(12): 2897-2906.
	Background: The polycystic ovary syndrome (PCOS) is the most common endocrine disorder found in women of reproductive age. Aim of the Study: The aim of this study is to clarify the effect of zinc, vitamin D, and metformin on poly cystic ovarian syndrome patients.Patients and methods: The study was carried out in Tikrit city from 1st of October 2021 to 1st of May 2022 included total of 90 sub-fertile and fertile PCOS women aged 24-35 years old who attend to the department of obstetrics and gynecology at Salah Al-Din General Hospital and private clinics. The PCOS patients were enrolled in a randomized clinical trial and divided into three equal groups. Group A (n:30) received 50 mg of zinc and 400 IU of vitamin D per day, orally. Group B (n:30) received the same as Group A, plus 1,500 mg/day of metformin orally. Group C (n:30) received 1,500 mg/day of metformin orally. Blood sample was taken from each women in the groups in the first visit (2-3 days of menses) before administration of treatment for determination of LH, FSH, serum zinc and vitamin D and base line pelvic songraphy was performed on 2nd and 3rd day from menstrual cycle to asses follicular and ovarian size. Pelvic sonography was performed from day 2 to day 3 of menstruation to asses ovarian and Follicular size. Follicular growth was categorized in to three groups according to the size of follicle using trans pelvic sonography at midcycle. Result(s): The study showed that the administration of Zinc+Vit D+ Metformin have a significant role in regularity of menses as 58% of PCOS women within group B (who received Zinc+Vit D+ Metformin) who were with irregular menstrual cycle became with regular menstrual cycle. The growth of follicles was significantly higher in Group B after treatment and pregnancy occurred in 13% of Group B who received Zinc+ Vit D+ Metformin. Conclusion(s): The study concluded that the administration of Zinc+VitD+Metforminhave beneficial effect in regularity of menstrual cycle decrease in BMI, LH, progesterone and enhance follicular response and increasing pregnancy rate.Copyright © 2022, Anka Publishers. All rights reserved.

Mullins, C. F., et al. (2022). "Pre-Outpatient Group Education and Assessment in Chronic Pain: A Systematic Review." Pain medicine (Malden, Mass.) 23(1): 89-104.
	BACKGROUND: Pre-outpatient interventions in chronic pain have the potential to improve patient self-management earlier in primary or secondary care, which may minimize pain chronicity and negative health outcomes. The literature for this is sparse, and there are no existing systematic reviews on this topic. METHODS: The purpose of this systematic review is to examine the evidence for pre-outpatient group interventions in chronic pain. RESULTS: We identified four studies that looked at this: two randomized control trials, one prospective observational study, and one descriptive study. We identified high-quality evidence that a pre-outpatient group intervention reduces waiting times, moderate-quality evidence that it results in reduced costs per patient, very low-quality evidence that it reduces health care utilization, and very low-quality evidence that it improves service throughput. There were moderate-to-low levels of participant engagement with the initiative, which varied across the included studies. For patient outcome measures, we found no evidence that a pre-outpatient group intervention improves pain intensity, very low-quality evidence that it improves pain-related interference, low-quality evidence that it increases use of pain management strategies and produces high satisfaction levels, low-quality evidence that it improves pain self-efficacy, and no evidence that it improves psychological distress. CONCLUSIONS: Group interventions before individual appointments have the potential to provide important improvements in service delivery, including improvements in waiting times and cost per patient. Benefits for patient outcome measures are less clear. Clinical heterogeneity and high levels of bias existed in the included studies. Further research is required so that meaningful conclusions can be made about these interventions.

Munno, G. M., et al. (2023). "Pelvic Organ Prolapse Syndrome and Lower Urinary Tract Symptom Update: What's New?" Healthcare (Basel, Switzerland) 11(10).
	(1) Background: This narrative review aimed to analyze the epidemiological, clinical, surgical, prognostic, and instrumental aspects of the link between pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), collecting the most recent evidence from the scientific literature. (2) Methods: We matched the terms "pelvic organ prolapse" (POP) and "lower urinary tract symptoms" (LUTS) on the following databases: Pubmed, Embase, Scopus, Google scholar, and Cochrane. We excluded case reports, systematic reviews, articles published in a language other than English, and studies focusing only on a surgical technique. (3) Results: There is a link between POP and LUTS. Bladder outlet obstruction (BOO) would increase variation in bladder structure and function, which could lead to an overactive bladder (OAB). There is no connection between the POP stage and LUTS. Prolapse surgery could modify the symptoms of OAB with improvement or healing. Post-surgical predictive factors of non-improvement of OAB or de novo onset include high BMI, neurological pathologies, age > 65 years, and the severity of symptoms; predictors of emptying disorders are neurological pathologies, BOO, perineal dysfunctions, severity of pre-surgery symptoms, and severe anterior prolapse. Urodynamics should be performed on a specific subset of patients (i.e., stress urinary incontinence, correct surgery planning), (4) Conclusions: Correction of prolapse is the primary treatment for detrusor underactivity and for patients with both POP and OAB.

Munns, L., et al. (2024). "The effects of yoga-based interventions on postnatal mental health and well-being: A systematic review." Heliyon 10(3): e25455.
	BACKGROUND: The postnatal period is a critical time for maternal mental health, presenting unique challenges and vulnerabilities. Identifying effective and accessible strategies to improve postnatal mental health and well-being is therefore crucial and could have substantial benefits for both mothers and babies, alongside broader implications for healthcare systems. Yoga is a potential intervention that has demonstrated notable benefits; however, a gap exists in systematically evaluating the existing literature on postnatal yoga-based interventions. This systematic review addresses this, aiming to comprehensively assess the impact of postnatal yoga on maternal mental health and well-being. METHODS: Six databases were searched using keywords "yoga", "yogic", "postnatal", "postpartum", "perinatal", "maternal", "mother*". Articles were considered if they were quantitative and evaluated a yoga or yoga-based intervention in postnatal samples. Study outcomes were extracted and synthesised descriptively. A quality assessment of studies was also conducted. FINDINGS: Of the 383 non-duplicated records that were identified, nine met criteria for full-text review. Only 6 met the inclusion criteria and so were included in the review. Across the 6 studies within this review, data from 377 adult women were included and looked at the outcomes of women in the USA, Northern Ireland, Taiwan and Turkey. The findings of the studies suggest that taking part in postnatal yoga is associated with decreased symptoms of depression, an increase in psychological well-being and quality of life. KEY CONCLUSIONS: Yoga-based interventions may offer a promising and effective intervention for maternal mental health and well-being. However, due to the limited number of studies, and a lack of consistency in study design and measures, more high-quality research is required to establish these effects and explore the potential benefits on other aspects of maternal well-being and infant outcomes.

Muñoz-Barreno, A., et al. (2021). "Comparative Effectiveness of Treatments for Bacterial Vaginosis: A Network Meta-Analysis." Antibiotics (Basel, Switzerland) 10(8).
	Bacterial vaginosis (BV) is a common vaginal dysbiosis in women of reproductive age. However, the cure rate for BV varies considerably and many women experience a relapse after the initial treatment. The present meta-analysis aimed to evaluate the clinical cure rates (CCRs) in randomized controlled trials (RCTs) through different therapies and administration routes. This meta-analysis included a final set of 25 eligible studies with a total of 57 RCTs and compared the effectiveness of BV treatments among non-pregnant and pregnant women. The initial range of CCRs varied greatly from 46.75% to 96.20% and the final pooled CCR was 75.5% (CI: 69.4-80.8) using the random model. The heterogeneity indices were Q = 418.91, I2 = 94.27%, and τ = 0.7498 ( p < 0.0001). No publication bias was observed according to Funnel plot symmetry and Egger's linear regression test ( p = 0.1097). To evaluate different variables, sub-group analysis, meta-regressions, and network meta-analysis were also realized. The highest P-scores in CCR were obtained by: (1) a combined therapy with local probiotic treatment and application of antibiotics by both administration route (oral clindamycin and local 5-nitroimidazole; P-score = 0.92); (2) a combined therapy with oral administration of 5-nitroimidazole and probiotic treatment (P-score = 0.82); (3) and a combined therapy with local administration of 5-nitroimidazole and oral probiotic treatment (P-score = 0.68). A clear-cut decision of the best BV treatment was not possible due to the heterogeneity of outcomes reported in the trials, indicating the necessity for a better characterization of RCTs. Finally, combined therapies suggested the reduction of the optimal concentration of antibiotics, and double phase treatments of antibiotics indicated an increment of CCRs in BV.

Muñoz-Gómez, E., et al. (2023). "Effectiveness of a Manual Therapy Protocol in Women with Pelvic Pain Due to Endometriosis: A Randomized Clinical Trial." Journal of Clinical Medicine 12(9).
	A randomized controlled trial was carried out to assess the effectiveness of a manual therapy protocol in terms of the clinical characteristics, quality of life, and emotional condition of the women with endometriosis-related pelvic pain. Forty-one women (mean age of 36.10 (6.97) years) with pelvic pain due to endometriosis were randomly divided into (i) a manual therapy group (MTG) ( n = 21) and (ii) a placebo group (PG) ( n = 20). Both groups received an 8-week intervention. Pain, lumbar mobility, endometriosis health profile, quality of life, depression and anxiety levels, and the patient's perception of change were assessed before (T0) and after (T1) the intervention, as well as at a one-month follow-up (T2) and a six-month follow-up (T3). The MTG significantly improved pain intensity, powerlessness, lumbar mobility, and physical quality of life at T1 ( p < 0.05). The results were maintained for pain intensity at T2 and T3. In addition, both the MTG and PG improved emotional wellbeing at T1 ( p < 0.05). Neither group improved in terms of social support, self-image, and depression and anxiety levels after the intervention ( p > 0.05). In conclusion, manual therapy may be an excellent complement to the gynecological treatment of endometriosis-related pelvic pain by alleviating pain and improving women's endometriosis health profile and physical quality of life.

Murakami, I., et al. (2023). "Effects of a fertility-sparing re-treatment for recurrent atypical endometrial hyperplasia and endometrial cancer: a systematic literature review." Journal of Gynecologic Oncology 34(4): e49.
	Objective: To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.; Methods: A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.; Results: After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).; Conclusion: This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.; Competing Interests: No potential conflict of interest relevant to this article was reported. (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Murakami, N., et al. (2022). "An Asian multi-national multi-institutional retrospective study comparing intracavitary versus the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical carcinoma." Journal of radiation research 63(3): 412-427.
	This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1-139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC. (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Muraoka, A., et al. (2021). "Impact of perioperative use of GnRH agonist or dienogest on ovarian reserve after cystectomy for endometriomas: a randomized controlled trial." Reproductive biology and endocrinology : RB&E 19(1): 179.
	BACKGROUND: Ovarian endometrioma is a common gynecological disease that is often treated with surgery or hormonal treatment. Ovarian cystectomy, a surgical procedure for ovarian endometrioma, can result in impaired ovarian reserve. METHODS: We conducted a randomized controlled trial to evaluate the efficacy of hormonal treatment [gonadotropin-releasing hormone agonist (GnRHa) or dienogest (DNG)] for preserving ovarian reserve after cystectomy for ovarian endometrioma. The primary endpoint was the level of serum Anti-Müllerian hormone (AMH) as a marker of ovarian reserve. RESULTS: Before and after laparoscopic surgery, 22 patients in the GnRHa group and 27 patients in the DNG group were administered hormonal treatment for a total of 4 months. After 1-year follow-up, >60% of the patients in the DNG group retained over 70% of their pretreatment AMH levels, whereas no patient in the GnRHa group retained their AMH levels after cystectomy (P < 0.01). Interleukin-6 (IL-6) is a key cytokine involved in inflammation. Compared with the GnRHa group, patients in the DNG group had lower IL-6 levels at the end of treatment. CONCLUSIONS: Our data revealed that DNG is more effective than GnRHa in preserving ovarian reserve after cystectomy of ovarian endometrioma. This is achieved through the reduction of the inflammatory response during the perioperative period and other endometriosis-related inflammatory reactions. TRIAL REGISTRATION: The registration number of this trial is UMIN-CTR, UMIN000018569, registered 6 August 2015, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021492 , and Japan Registry of Clinical Trials, jRCTs041180140, registered 29 March 2019, https://jrct.niph.go.jp/en-latest-detail/jRCTs041180140 . This randomized controlled trial was conducted in accordance with the CONSORT guidelines.

Murina, F., et al. (2023). "Effectiveness of Two Transcutaneous Electrical Nerve Stimulation (TENS) Protocols in Women with Provoked Vestibulodynia: A Randomized Controlled Trial." Medical sciences (Basel, Switzerland) 11(3).
	Background: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD.; Methods: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements.; Results: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% ( p = 0.003) and 23.1% in Group 2 ( p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant.; Conclusions: Our findings showed the potential of TENS in the treatment of VBD.

Musa, A., et al. (2023). "Superior Hypogastric Nerve Blockade for Uterine Artery Embolization: A Systematic Review." Journal of vascular and interventional radiology : JVIR 34(10): 1827.
	Superior hypogastric nerve block (SHNB) has potential to reduce pain following uterine artery embolization (UAE). However, existing studies are limited by design, sample size, or conflicting results. A systematic review of the literature was performed. Outcomes included technical success, time to complete SHNB, time under fluoroscopy, procedure time, time to recovery, needle repositioning, same-day discharge, readmission, pain, analgesic consumption, and adverse events. Of 15 included studies, the same-day discharge rate was 98.8%, and readmission rate was 6.9%. The mean pain score was 3.4 in patients who received SHNB compared to 4.3 among controls. Of patients who received SHNB, 46.7% did not require further pain medication. Major adverse events occurred in 0.4% of patients. Early clinical studies suggest that SHNB appears to reduce pain and analgesic consumption in patients undergoing UAE. Additional randomized trials are needed to confirm these findings. (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Musacchio, L., et al. (2022). "MITO 25.1: A RANDOMIZED, MOLECULAR DRIVEN PHASE II TRIAL OF CARBOPLATIN-PACLITAXELBEVACIZUMAB VS CARBOPLATIN-PACLITAXELBEVACIZUMAB- RUCAPARIB VS CARBOPLATINPACLITAXEL- RUCAPARIB, SELECTED ACCORDING TO HRD STATUS, IN PATIENTS WITH ADVANCED OVARIAN CANCER." International Journal of Gynecological Cancer 32(Supplement 3): A239.
	Objectives PARP inhibitors alone and in combination with Bevacizumab have shown significant clinical benefit as maintenance therapy in ovarian cancer (OC) patients regardless BRCA mutations and in homologous-recombination deficiency (HRD) positive women, respectively. However, despite the improvements in the therapeutic algorithm of OC over the years, the best treatment in HRD positive patients and the preferred treatment in HRD negative tumors have not been well defined. MITO 25.1 aims to evaluate the best first line treatment in the different molecular subgroups, evaluated with Foundation Medicine LOH test. Methods MITO 25.1 is a multicenter, randomized, phase II study that will evaluate the effect of Carboplatin-Paclitaxel- Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib on progression-free survival (PFS) in OC patients treated according to HRD status. HRD negative patients will be randomized in ARM A to receive Carboplatin + Paclitaxel + Bevacizumab q21 followed by Bevacizumab q 21 or in ARM B to receive Carboplatin + Paclitaxel q 21 followed by Rucaparib as maintenance. HRD positive patients will be randomized in ARM B or in ARM C to receive Carboplatin + Paclitaxel + Bevacizumab q21 followed by Bevacizumab + Rucaparib as maintenance. The primary endpoint will be PFS. Results Trial in progress.there are no available results at the time of submission. Conclusions Trial in progress:there are no available conclusions at the time of submission.

Musacchio, L., et al. (2022). "MITO 25.1: a RANDOMIZED, MOLECULAR DRIVEN PHASE II TRIAL OF CARBOPLATINPACLITAXEL- BEVACIZUMAB VS CARBOPLATIN-PACLITAXEL-BEVACIZUMABRUCAPARIB VS CARBOPLATIN-PACLITAXELRUCAPARIB, SELECTED ACCORDING TO HRD STATUS, IN PATIENTS WITH ADVANCED (STAGE III B-C-IV) OVARIAN, PRIMARY PERITONEAL AND FALLOPIAN TUBE CANCER." International Journal of Gynecological Cancer 32: A347‐A348.
	Introduction/Background Poly (ADP‐ribose) polymerase (PARP) inhibitors alone and in combination with Bevacizumab have shown significant clinical benefit as maintenance therapy in women with newly diagnosed ovarian cancer (OC) regardless BRCA mutational status and in homologous‐recombination deficiency (HRD) positive patients, respectively. However, despite the remarkable improvements in the therapeutic algorithm of OC disease over the years, the best first line treatment is still controversial. Methodology MITO 25.1 is a multicenter, randomized openlabel, phase II study comparing Carboplatin‐Paclitaxel‐Bevacizumab vs Carboplatin‐Paclitaxel‐Bevacizumab‐Rucaparib vs Carboplatin‐ Paclitaxel‐Rucaparib.Eligible patients, with histological confirmed high grade serous or endometrioid advanced OC, will be randomized in a 1:1 ratio according to HRD status. Results HRD negative patients: ARM A: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 + Bevacizumab 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bevacizumab 15 mg/ kg q 21 for 17 cycles, ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance HRD positive patients: ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/ m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance: ARM C: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 + Bevacizumab 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bevacizumab 15 mg/ kg q 21 days for 16 cycles + Rucaparib 500 mg part BID q 28 for 24 cycles as maintenance Conclusion The primary endpoint will be PFS. The secondary endpoints will be overall survival (OS), PFS2, adverse events according to CTCAE 5.0 and patient‐reported outcome. Patients recruiting started in March 2021. To date, 159 of the 300 patients planned have been enrolled.

Musacchio, L., et al. (2022). "MITO 25.1: A RANDOMIZED, MOLECULAR DRIVEN PHASE II TRIAL OF CARBOPLATINPACLITAXEL- BEVACIZUMAB VS CARBOPLATIN-PACLITAXEL-BEVACIZUMABRUCAPARIB VS CARBOPLATIN-PACLITAXELRUCAPARIB, SELECTED ACCORDING TO HRD STATUS, IN PATIENTS WITH ADVANCED (STAGE III B-C-IV) OVARIAN, PRIMARY PERITONEAL AND FALLOPIAN TUBE CANCER." International Journal of Gynecological Cancer 32(Supplement 2): A347-A348.
	Introduction/Background Poly (ADP-ribose) polymerase (PARP) inhibitors alone and in combination with Bevacizumab have shown significant clinical benefit as maintenance therapy in women with newly diagnosed ovarian cancer (OC) regardless BRCA mutational status and in homologous-recombination deficiency (HRD) positive patients, respectively. However, despite the remarkable improvements in the therapeutic algorithm of OC disease over the years, the best first line treatment is still controversial. Methodology MITO 25.1 is a multicenter, randomized openlabel, phase II study comparing Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin- Paclitaxel-Rucaparib.Eligible patients, with histological confirmed high grade serous or endometrioid advanced OC, will be randomized in a 1:1 ratio according to HRD status. Results HRD negative patients: ARM A: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 + Bevacizumab 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bevacizumab 15 mg/ kg q 21 for 17 cycles, ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance HRD positive patients: ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/ m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance: ARM C: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 + Bevacizumab 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bevacizumab 15 mg/ kg q 21 days for 16 cycles + Rucaparib 500 mg part BID q 28 for 24 cycles as maintenance Conclusion The primary endpoint will be PFS. The secondary endpoints will be overall survival (OS), PFS2, adverse events according to CTCAE 5.0 and patient-reported outcome. Patients recruiting started in March 2021. To date, 159 of the 300 patients planned have been enrolled.

Musacchio, L., et al. (2022). "MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis." Cancer Treatment Reviews 110: 102458.
	Background: Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status.; Methods: In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis.; Results: A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (I 2 = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 - 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I 2 = 85 %; P = 0.009).; Conclusions: Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mussi Marcela Chagas, L., et al. (2022). "Superior Hypogastric Nerve Block (SHNB) for pain management in Uterine Artery Embolization (UAE): a literature review." Rev. méd. Minas Gerais 31: 31213-31213.
	Introduction: Uterine Artery Embolization (UAE) is a therapeutic option in the treatment of symptomatic uterine fibroids; however, post-procedure pain imposes as a great challenge in this technique. In this context, the Superior Hypogastric Nerve Block (SHNB), already used in the treatment of chronic pelvic pain associated with malignancy, presents itself as an option for intraprocedural intervention, to improve patients' recovery and to promote UAE in the clinical setting. Objective: to perform an integrative literature review about the effectiveness of SHNB in pain management after UAE. Methods: databases PubMed, The Cochrane Library, Lilacs and Medline were assessed using the combination of the terms "uterine artery embolization", "pain" and "superior hypogastric block". Clinical studies were included once available in full text, with adult patients submitted to UAE, whose objective was to evaluate the use of SHNB and its impact in post-procedure pain. Review articles, letters to the editor, and publication in conference proceedings were excluded. Results: 8 articles were found, most of them retrospective, indicated SHNB's consistency in terms of short-term therapeutic success and pain reduction. The single reported complication evolved satisfactorily. Conclusions: SHNB has the potential to improve pain management after UAE, which can positively impact recovery time and quality, with reduced pain and consumption of opioids in the postoperative period. Benefits like these can enhance the embolization procedure as an alternative to be considered for the treatment of symptomatic fibroids for women candidates for uterine preservation.

Mutch, D., et al. (2024). "Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti-PD-L1, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer." Cancer.
	Background: This phase 1b study (ClinicalTrials.gov identifier NCT03695380) evaluated regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer (PSROC). Method(s): Patients with PSROC who had received one or two prior treatment lines were treated with 28-day cycles of cobimetinib 60 mg daily (days 1-21) plus niraparib 200 mg daily (days 1-28) with or without atezolizumab 840 mg (days 1 and 15). Stage 1 assessed safety before expansion to stage 2, which randomized patients who had BRCA wild-type PSROC to receive either doublet or triplet therapy, stratified by genome-wide loss of heterozygosity status (<16% vs. >=16%; FoundationOne CDx assay) and platinum-free interval (>=6 to <12 vs. >=12 months). Coprimary end points were safety and the investigator-determined objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Potential associations between genetic parameters and efficacy were explored, and biomarker profiles of super-responders (complete response or those with progression-free survival [PFS] >15 months) and progressors (disease progression as the best response) were characterized. Result(s): The ORR in patients who had BRCA wild-type PSROC was 35% (95% confidence interval, 20%-53%) with the doublet regimen (n = 37) and 27% (95% confidence interval, 14%-44%) with the triplet regimen (n = 37), and the median PFS was 6.0 and 7.4 months, respectively. Post-hoc analyses indicated more favorable ORR and PFS in the homologous recombination-deficiency-signature (HRDsig)-positive subgroup than in the HRDsig-negative subgroup. Tolerability was consistent with the known profiles of individual agents. NF1 and MKNK1 mutations were associated with sustained benefit from the doublet and triplet regimens, respectively. Conclusion(s): Chemotherapy-free doublet and triplet therapy demonstrated encouraging activity, including among patients who had BRCA wild-type, HRDsig-positive or HRDsig-negative PSROC harboring NF1 or MKNK1 mutations.Copyright © 2024 F. Hoffmann-La Roche. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Mutombo Alex, B., et al. (2019). "Efficacy of commercially available biological agents for the topical treatment of cervical intraepithelial neoplasia: a systematic review." Systematic Reviews 8(1): 132.
	Background: Cervical cancer is a major public health issue in the world, especially in developing countries. It can be prevented through vaccination against HPV (primary prevention) and through screening and treatment of cervical intraepithelial neoplasia (CIN) (secondary prevention). Surgical methods for treatment of CIN are linked to complications such as bleeding and adverse pregnancy outcomes. Furthermore, these methods are not generally available in resource-poor settings. Therefore, topical agents for local application on the cervix have been used since decades to overpass complications and limitations of the surgical methods.; Aims: Review of the literature on the efficacy of commercially available biological agents used for topical treatment of cervical intraepithelial neoplasia (CIN).; Methods: A systematic search through PubMed and the Cochrane database was performed up to December 2017, using the medical subheadings (MesH) for topical agent, treatment, and cervical intraepithelial neoplasia. Appropriate inclusion/exclusion criteria have been used for the selection of eligible clinical studies. Clinical studies containing a minimum of 20 women, aged 18-50 with a diagnosis of CIN 1-3, and at least a 4 weeks follow-up after the end of the topical treatment were included.; Results: The initial electronic database search resulted in a total of 849 articles. After screening titles and abstracts, 62 articles were selected as potential studies. Of these, six articles were included in the review after reading the full text: two were on 5-FluoroUracil, two on trans retinoic acid, one on Imiquimod, and one on Cidofovir. The reported regression/remission rates for CIN differed among studies. In CIN2 patients, the overall remission rate ranged between 43 and 93% for the active agents.; Conclusion: Among the topical agents studied, 5-FluoroUracil showed good remission rates above 80%. Varying results seen in this review is due to the differences in quality of the design between studies. Large-scale and less biaised studies are needed to elucidate the true efficacy and safety of topical agents in the treatment of CIN.

Muxuan, C., et al. (2021). "Probiotics are a good choice for the treatment of Bacterial Vaginosis: a meta-analysis of randomized controlled trial."
	
Muzii, L., et al. (2023). "The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis." Reproductive sciences (Thousand Oaks, Calif.) 30(11): 3135-3143.
	The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness. (© 2023. The Author(s).)

Muzii, L., et al. (2020). "Efficacy of Antibiotic Prophylaxis for Hysteroscopy: A Meta-Analysis of Randomized Trials." Journal of Minimally Invasive Gynecology 27(1): 29-37.
	Objective: To assess the efficacy and side effects of antibiotic prophylaxis compared with placebo or no treatment in women undergoing hysteroscopy.; Data Sources: A structured search was carried out in PubMed-Medline, Embase, and Cochrane Controlled Trials Register databases through December 31, 2018.; Methods of Study Selection: The search included a combination of the following terms: "hysteroscopy," "endoscopic surgery," "antibiotic prophylaxis." The following outcomes were selected: postoperative fever, infection rate, pelvic inflammatory disease (PID) and abscess occurrence, postoperative antibiotic requirement, and side effects occurrence (lower abdominal pain, vomiting, diarrhea, anaphylactic reaction). A random-effects model was used at meta-analysis. Study quality and bias risk were assessed with the Cochrane tool.; Tabulation, Integration, and Results: Five randomized controlled trials comparing efficacy of antibiotic prophylaxis with placebo or no treatment were included in the meta-analysis. Overall, pooled incidence of events was very low in both groups (fever, 3.79% vs 1.8%; overall infection, .52% vs .58%; postoperative antibiotic therapy, 1.18% vs 1.32%; and lower abdominal pain, 12.46% vs 9.31%). Moreover, the incidence of serious infections requiring further actions (PID or abscess) appeared to be extremely low (.2% in pretreated women and none in control groups). No one trial individually or the pooled analysis showed a statistically significant benefit of antibiotics prophylaxis over placebo for the outcome considered.; Conclusion: The use of antibiotics appears not to be beneficial to prevent infection after hysteroscopy; however, the lack of high-quality studies makes it difficult to draw firm conclusions. Considering the very low infection rate highlighted after hysteroscopic procedures, a difference will probably never be proven in a randomized trial. A larger population and program data to confirm these results are therefore warranted. (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Muzny, C. A., et al. (2022). "Single-Dose Oral Secnidazole for Treatment of Trichomoniasis in Women With BV Co-infection." Obstetrics and Gynecology 139(SUPPL 1): 35S.
	INTRODUCTION: Bacterial vaginosis (BV) and trichomoniasis are the most common causes of vaginitis. Both infections are associated with increased risk for HIV/STIs and adverse reproductive health outcomes. Coexistence of BV pathogens and Trichomoniasis vaginalis is common, with co-infection rates of 60-80%. In this secondary analysis of clinical trial data of single-dose oral secnidazole (SEC) for the treatment of women with trichomoniasis, we review a subset of women with both trichomoniasis and BV. METHOD(S): In an institutional review board-approved study, women with clinically diagnosed trichomoniasis were randomized to SEC 2 g oral granules or placebo at baseline (Visit 1). At Visit 2 (days 6-12), patients were evaluated for test-of-cure by T. vaginalis culture and were provided the opposite treatment. The primary endpoint was microbiological cure (negative culture for T. vaginalis) at the TOC visit. BV was clinically diagnosed at both visits using Amsel's criteria. RESULT(S): Overall, 147 women were enrolled; the modified intentto- treat (mITT) population included 131 randomized patients. Cure rates were 92.2% and 1.5% for SEC and placebo (P<.001). The perprotocol population included 119 patients. Cure rates were 94.9% and 1.7% for SEC and placebo, respectively. In the mITT subgroup of women with BV based on at least three Amsel criteria (n=79), cure rates for trichomoniasis were 97.67% (42/43) for SEC and 0/36 for placebo. CONCLUSION(S): Single-dose oral SEC was highly effective in treating trichomoniasis in women with BV co-infection. Co-infection is common and appropriate treatment for both infections is critical. SEC is the only FDA-approved single-dose treatment for BV in women and trichomoniasis in women and men.

Muzny Christina, A., et al. (2022). "A Comparison of Single-Dose Versus Multidose Metronidazole by Select Clinical Factors for the Treatment of Trichomonas vaginalis in Women." Sexually Transmitted Diseases 49(3): 231-236.
	Background: In a randomized controlled trial of 2 g (single-dose) metronidazole (MTZ) versus 500 mg twice daily for 7 days (multidose) for Trichomonas vaginalis treatment, multidose was superior. We examined if the effect was similar by select clinical factors to determine if treatment recommendations could be targeted.; Methods: The primary outcome was T. vaginalis repeat infection at test-of-cure (TOC) 4 weeks after completion of therapy. Analyses were stratified by T. vaginalis history, baseline genital symptoms, and concurrent diagnosis of bacterial vaginosis (BV) per Nugent score at baseline.; Results: Women who returned for TOC (n = 540) were included. At baseline, 52.9% had a self-reported history of T. vaginalis; 79.3%, genital symptoms; 5.8%, a gonorrhea diagnosis; and 47.5%, BV. During follow-up, 97.4% took all MTZ as instructed and 34.5% had interval condomless sex with a baseline partner. At TOC, 14.8% tested positive for T. vaginalis. In stratified analysis, women randomized to single-dose MTZ had a higher rate of TOC T. vaginalis positivity than those randomized to multidose if they were symptomatic at baseline (21.4% vs. 10.8%, P = 0.003) or had a reported history of T. vaginalis (24.1% vs. 12.6%, P = 0.01). Test-of-cure T. vaginalis positivity was higher for women receiving a single dose (18.9%) versus multidose (10.8%), irrespective of baseline BV status (P > 0.06). In multivariable analysis, only a history of T. vaginalis and single-dose MTZ were independently associated with a positive TOC for T. vaginalis.; Conclusions: Although multidose MTZ is recommended for all women with T. vaginalis, it is especially important for women with a T. vaginalis history and, given high posttreatment infection rates, a TOC should be performed.; Competing Interests: Conflict of Interest and Sources of Funding: C.A.M. is a consultant for Lupin Pharmaceuticals, BioFire Diagnostics, Cepheid, and PhagoMed. She has also received research funding support from Lupin Pharmaceuticals and Abbott Molecular as well as speaker honoraria from Abbott Molecular, Cepheid, Roche Diagnostics, and Becton Dickinson. L.A.M. has received honoraria for his role as a consultant to Gilead Sciences, ViiV Healthcare, Roche, and Merck. He has received research grants from Gilead Sciences, ViiV Healthcare/GSK, Janssen, Binx Health (Atlas Genetics), Becton Dickinson, Rheonix, Click Diagnostics, Roche, Evofem, Westat, and Lupin Pharmaceuticals. R.A.L. has conducted clinical trials for Cepheid and Hologic and is a consultant for Roche and Merck. N.S., D.H.M., and P.K. have nothing to disclose. (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Muzny Christina, A., et al. (2023). "Efficacy of single-dose oral secnidazole for the treatment of trichomoniasis in women co-infected with trichomoniasis and bacterial vaginosis: a post hoc subgroup analysis of phase 3 clinical trial data." BMJ Open 13(8): e072071.
	Objectives: Bacterial vaginosis (BV) and trichomoniasis are the most common causes of vaginitis. Both infections are associated with increased risk of acquisition and transmission of HIV and other sexually transmitted infections as well as adverse reproductive health outcomes. Co-infection is common, with rates ranging from 60% to 80%. We evaluated the efficacy of single-dose oral secnidazole 2 g for the treatment of trichomoniasis in a subgroup of women co-infected with BV and trichomoniasis.; Design: Post hoc analysis of data from a phase 3 randomised, double-blind, placebo-controlled, delayed-treatment study.; Setting: 10 centres in the USA.; Participants: Subgroup of women (aged ≥12 years) with a confirmed diagnosis of Trichomonas vaginalis and co-infection with BV clinically diagnosed using Amsel's criteria.; Intervention: Single dose of secnidazole 2 g or placebo.; Outcome Measures: The primary efficacy outcome was the microbiological cure (negative culture for T. vaginalis ) at the test of cure (TOC) visit 6-12 days after dosing in the modified intent-to-treat population (mITT). At TOC, participants received the opposite treatment.; Results: Of the 131 T . vaginalis -infected participants in the mITT, 79 (60.3%) met ≥3 Amsel's criteria for BV at enrolment. Microbiological cure rates for trichomoniasis at TOC among this subgroup of women were 97.7% (42/43) for secnidazole and 0% (0/36) for placebo.; Conclusion: Single-dose oral secnidazole 2 g was highly efficacious in curing trichomoniasis in women co-infected with BV. Appropriate and effective treatment options for co-infection are essential for reducing transmission and reinfection. Secnidazole is the only single-dose medication approved by the Food and Drug Administration for the treatment of BV in women and trichomoniasis in women and men.; Trial Registration Number: ClinicalTrials.gov, NCT03935217; post-results.; Competing Interests: Competing interests: CAM has received research grant support from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences, Inc, Visby Medical, and Abbott Molecular; is a consultant for Lupin Pharmaceuticals, BioNTech, Scynexis, and Cepheid; and has received honoraria from Visby Medical, Elsevier, Abbott Molecular, Cepheid, Roche Diagnostics, and Lupin Pharmaceuticals. OTVG has received research grant support from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences, and Abbott Molecular and has served on a scientific advisory board for Scynexis; GK is an employee of Lupin Pharmaceuticals, Inc. SC has received consulting fees from Lupin Pharmaceuticals, Inc. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Myers Stephen, P. and V. Vigar (2019). "The State of the Evidence for Whole-System, Multi-Modality Naturopathic Medicine: A Systematic Scoping Review." Journal of alternative and complementary medicine (New York, N.Y.) 25(2): 141-168.
	Objective: To summarize the current state of the research evidence for whole-system, multi-modality naturopathic medicine.; Design: A systematic search for research articles from around the world was undertaken using MEDLINE, Embase, CINAHL, AMED, and WHO regional indexes. Naturopathic journals and gray literature were hand searched. No language restrictions were imposed.; Interventions: All human research evaluating the effectiveness of naturopathic medicine, where two or more naturopathic modalities are delivered by naturopathic clinicians, were included in the review. Case studies of five or more cases were included.; Results: Thirty-three published studies (n = 9859) met inclusion criteria (11 American; 4 Canadian; 6 German; 7 Indian; 3 Australian; 1 United Kingdom; and 1 Japanese) across a range of mainly chronic clinical conditions. The studies predominantly showed evidence for the efficacy of naturopathic medicine for the conditions and settings in which they were based.; Conclusions: To date, research in whole-system, multi-modality naturopathic medicine shows that it is effective for treating cardiovascular disease, musculoskeletal pain, type 2 diabetes, polycystic ovary syndrome, depression, anxiety, and a range of complex chronic conditions.

Myneni, R., et al. (2021). "Thyroxine Replacement for Subfertile Females With Subclinical Hypothyroidism and Autoimmune Thyroiditis: A Systematic Review." Cureus 13(8): e16872.
	The second most prevalent endocrine condition affecting women of reproductive age is thyroid disease. The difference between an increased thyroid-stimulating hormone (TSH) concentration and a normal free thyroxine hormone level is used to identify subclinical hypothyroidism. Thyroid autoantibodies, independent of thyroid hormone levels, are used to diagnose autoimmune thyroid disease (ATD). Thyroxine can help infertile women with these two types of thyroid illnesses have better birth outcomes during fertility treatment. We performed a systematic review using PubMed (Medline) as a major database and some other sources EMBASE, the Cochrane Library, Web of Science, Scopus, and Science Direct. We concentrated on four studies, including 806 patients. Our goal is to investigate the efficacy and risks of levothyroxine therapy in infertile women who are receiving fertility treatments and have subclinical hypothyroidism or adequate thyroid function as well as thyroid autoimmunity (euthyroid autoimmune thyroid disorder). Thyroid activity in hypothyroid women should be tracked at pregnancy confirmation and closely monitored during the pregnancy. Early in pregnancy, the dosage of levothyroxine (LT4) can be raised. To ensure optimum TSH levels during breastfeeding, we recommend that patients who are followed in the primary sector have their LT4 dose increased by their general practitioner before their first referral to an endocrinological outpatient clinic. It's important to pay more attention to and track pregnant women with hypothyroidism, who consider pregnancy, to get the best results. LT4 therapy can help subfertile women with subclinical hypothyroidism who are having in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) since it improves embryo growth, implantation rate, and live birth rate.

Na, L. I. (2019). "Meta Analysis of Effects of Electroneedle Combined with Pelvic Bottom Muscle Exercise in Treatment of Stress Incontinence in Women." 新中医 51(8): 208-211.
	Objective: Systematic evaluation of the effect of electroneedle combined with pelvic floor muscle exercise on the treatment of patients with stress urinary incontinence (SUI) in women. Method: Computer-retrieval Cochrane Library, PubMed, Medical Literature Retrieval Service System (Excerpt) Medica Database, Embase), China Knowledge, China Biomedical Documentation Database, and Wanfang Database to find a randomized controlled trial or experimental study of electroneedle and pelvic floor muscle exercise therapy and effect evaluation in female SUI patients. into 8 literature, a total of 589 study subjects.Meta analysis results show that electroneedle combined with pelvic floor muscle exercise significantly reduces the incontinence questionnaire of the International Advisory Committee on Urinary Incontinence (International Consultation on Incontinence-Quesnaire: Short Form , ICIQ-SF) integrals [MD=-2.59,95% CI (-3.12, -2.06), P≈ 0.05], reduced 1h leakage in patients [MD=-3.56,95% CI (-3.85, -3.27), P≈ 0.05], significantly improving the effectiveness of treatment in female SUI patients [OR=6.12,95% CI ( 3.27,11.43), P0.05]. Conclusion: Electroneedle combined with pelvic floor muscle exercise in female SUI patients can improve ICIQ-SF scale integral, 1h leakage, and more effective treatment is worth promoting.

Na, Z., et al. (2023). "Efficacy and safety of acupuncture and moxibustion for dysmenorrhea:a protocol of overview for systematic reviews."
	
Nabi, A., et al. (2023). "Study of Clomiphene Citrate Vs Letrozole For Ovulation Induction in Infertile PCOS Women." European Journal of Molecular and Clinical Medicine 10(1): 2031-2037.
	Background: This study was conducted to compare Clomiphene Citrate Vs Letrozole for ovulation induction in infertile PCOS women. Method(s): This study includes 200 infertile PCOS women attending GOPD Department of Obstetrics and Gynaecology, NMCH from January 2021 to December 2022. The patients were divided in two groups. 100 women received 100mg CC once daily from D2-D6 of cycle. 100 women received 2.5 mg Letrozole once daily from D2-D6 of cycle - both groups for 3 cycles each. Follicular monitoring was done daily from D12-D16 of cycle. Inj HCG 5000IU was administrated IM when atleast one follicle with a mean diameter of more than equal to 18 mm was achieved. After 36 hours of HCG administration ovulation was confirmed on ultrasound. Result(s): Both groups were comparable with respect to age, BMI and mean duration of infertility. Both groups were compared with respect to number of follicles, mean diameter of largest follicle, rate of ovulation, mean endometrial thickness and serum progesterone level on D21 of cycle. The number of mature follicle was significantly lower but but the endometrial thickness and ovulation rate was significantly higher in Letrozole group than CC group. Conclusion(s): My study showed that Letrozole has better ovulation rate than CC and should be considered as 1st line drug for ovulation induction in infertile PCOS women.Copyright © 2023 Ubiquity Press. All rights reserved.

Nachtigall, L., et al. (2022). "Efficacy of Topical Sinecatechins Ointment for Provoked Vestibulodynia in Post-Menopausal Women: A Randomized Double-blind Placebo-Controlled Clinical Trial." Journal of Sexual Medicine 19(Supplement 3): S28-S29.
	Introduction Introduction: There is an unfulfilled need in post-menopausal women for a non-hormonal therapeutic to alleviate provoked vestibulodynia. Most post-menopausal women choose not to use estrogens and for others with estrogen sensitive malignancies estrogens are contraindicated. Vestibulodynia may persist despite the use of estrogens for post-menopausal women with vulvovaginal atrophy. Others experience vestibulodynia in the absence of vulvovaginal atrophy. Objective Objective: To determine efficacy of low dose, topical sinecatechins ointment, an FDA approved, antiproliferative, botanical drug derived from green tea, in reducing provoked vestibulodynia in sexually active postmenopausal women. Methods Methods: 32 postmenopausal sexually active women with a chief complaint of secondary provoked vestibulodynia were studied. Vestibulodynia was evaluated by standardized Q-TIP Testing and subjective reporting with a pain intensity at least a 7 on a 0- 10 point Numerical Rating Scale (NRS) where (0) no pain; (1-3) mild pain; (4-6) moderate pain;(7-9) significant pain; (10) severe pain. Subjects were evaluated by the gynecologist every 2-3 weeks for a total of 3 office visits during which vaginal pH and vaginal maturation index were performed. Subjects applied 1/2 inch of ointment once daily (5% sinecatechins, 10% sinecatechins or placebo) to their vulvar vestibule, avoiding the urethral introitus. Subjects were instructed to immediately report any irritation and to reduce their use to three times per week. Results There was no significant difference in the average vestibular pain between groups, (placebo, 5%, 10% sinecatechins ointment) at baseline. Both 5% and 10% active drug groups showed a progressive decrease in the one-way ANOVA P-Values with each visit, indicating a greater degree of pain reduction with continued use of the active study drug. Based on the Q-TIP and NRS, the 5% sinecatechins group demonstrated early pain reduction at Visit 2, while the 10% sinecatechins group demonstrated pain reduction by final Visit 3, most likely attributed to irritation experienced by several subjects using 10% which resolved by the final visit with decreased frequency of use to no more than 3x/week. All study groups showed no significant change in vaginal maturation index or vaginal pH between initial and final visits. Although not the primary objective of this clinical trial, several subjects indicated that topical 10% sinecatechins ointment used 3x/week increased sexual arousal, increased lubrication and/or decreased latency to orgasm without causing irritation. Conclusions Topicals sinecatechins ointment, significantly reduced provoked vestibulodynia in postmenopausal women offering a novel therapeutic alternative for the alleviation of vestibulodynia for women with a history of an estrogen sensitive malignancy, including those on an aromatase inhibitor. Sinecatechins ointment may be used adjunctively for women successfully using estrogens to treat vaginal atrophy to alleviate persistent vestibulodynia and enhance sexualexperience. The observed clinical effects of topical sinecatechins ointment on reducing vestibulodynia was dependent on both the concentration of sinecatechins and the frequency of application. Additional clinical trials for pre- and post-menopausal women with topical sinecatechins ointment as an adjunctive or primary therapeutic for sexual pain and arousal and orgasm are needed.

Nader, A., et al. (2021). "Drug-Drug Interaction Studies of Elagolix with Oral and Transdermal Low-Dose Hormonal Add-Back Therapy." Clinical pharmacokinetics 60(1): 133-143.
	Background and Objective: Elagolix is an oral, non-peptide, gonadotropin-releasing hormone receptor antagonist. It is approved for the treatment of moderate-to-severe pain associated with endometriosis and is being investigated for the treatment of heavy menstrual bleeding associated with uterine fibroids. Use of low-dose hormonal add-back therapy can reduce hypoestrogenic effects associated with elagolix, thus there is a need to determine if there is a pharmacokinetic interaction between elagolix and low-dose hormonal add-back therapy. Method(s): Two multiple-dose, open-label, single-sequence, non-randomized studies for elagolix 300 mg twice daily with oral (n = 24) and transdermal (n = 36) low-dose add-back therapy (estradiol [E2]/norethindrone acetate [NETA]; 1 mg/0.5 mg oral and 0.51 mg/4.8 mg transdermal) in healthy postmenopausal women were conducted, with pharmacokinetic sampling for E2, estrone (E1), and NETA up to 72 or 96 h after dosing. Pharmacokinetic parameters for hormones were estimated using noncompartmental methods. Result(s): No change in norethindrone maximum plasma concentration or area under the concentration-time curve was observed when oral E2/NETA was administered with elagolix. For E2, there was a 2-fold increase in maximum plasma concentration and a 1.5-fold increase in the area under the concentration-time curve, and for E1 there was a 1.7-fold increase in maximum plasma concentration when oral E2/NETA was administered with elagolix. Exposures for norethindrone, E2, and E1 were unchanged when transdermal E2/NETA was applied with elagolix administration. Conclusion(s): Although changes in E2/E1 exposures were observed when oral E2/NETA was co-administered with elagolix, these changes are not considered clinically relevant; and no dose adjustments are recommended when elagolix is co-administered with oral or transdermal low-dose add-back therapy.Copyright © 2020, Springer Nature Switzerland AG.

Nadia, C., et al. (2023). "A systematic review and guideline for the diagnosis, treatment and follow-up of pre-malignant and malignant gestational trophoblastic disease (GTD)."
	
Nadia, M. and A. Heather (2022). "Hormone therapy for sexual function in perimenopausal and postmenopausal women: a systematic review of literature published from 2013 (protocol)."
	
Nadjarzadeh, A., et al. (2021). "Effect of hypocaloric high-protein, low-carbohydrate diet supplemented with fennel on androgenic and anthropometric indices in overweight and obese women with polycystic ovary syndrome: A randomized placebo-controlled trial." Complementary Therapies in Medicine 56: 102633.
	OBJECTIVE: The aim of this study was to evaluate the effect of hypocaloric high-protein, low-carbohydrate weight loss diet supplemented with fennel on anthropometric and androgen indices in overweight and obese women with polycystic ovary syndrome (PCOS). METHODS: A randomized controlled trial with a factorial design was performed on sixty-four overweight/obese women with PCOS. Participants were randomly allocated to four groups (n = 16 per group) as follows: 1) hypocaloric standardize diet + fennel (2 capsule/day) (HSDF), 2) hypocaloric high-protein diet + fennel (2 capsule/day) (HHPF), 3) hypocaloric standardize diet + placebo (HSDP), and 4) hypocaloric high-protein diet + placebo (HHPP). RESULTS: The mean (SD) age of the participants was 28.54 (6.80) years and body mass index was 32.24 (4.65) kg/m2. At the end of intervention, protein intake was 20.43 % in the groups that received a high-protein diet versus 16.37 % in the standard diet groups (P < 0.001). Combination of hypocaloric high-protein diet and fennel capsule did not significantly affect change in outcomes compared with groups not receiving them. There was a significant interaction between hypocaloric high-protein diet and fennel on weight (P = 0.019). CONCLUSION: A hypocaloric high-protein diet along with fennel supplementation could not provide additional improvements in anthropometric and androgen indices among PCOS women. Further studies are required to more precisely elucidate these findings.

Nag, S., et al. (2021). "Panniculectomy Performed in Conjunction With Gynecologic Surgery in Obese and Morbidly Obese Patients: A National Surgical Quality Improvement Program Analysis and Systematic Review of the Literature." Annals of plastic surgery 87(5): 600-605.
	INTRODUCTION: Panniculectomy is a common procedure in plastic surgery, often performed after massive weight loss and in morbidly obese patients. It is also performed in combination with various gynecologic procedures based on the rational that it will reduce complication rates and benefit the patient (Am J Obstet Gynecol, 2000. 182, 1502-1505; J Gynecol Technol, 1997;3:9-16; J Am Coll Surg, 1995). These and other studies fail to provide proof of these claims for a number of reasons, including study design, lack of a control group and the inclusion of nonmorbidly obese patients (J Am Coll Surg, 1995; Gynecol Oncol, 1998, 70, 80-86; Int J Gynecol Cancer, 2015;25(8):1503-1512). Recent medical practice has focused increasingly on minimizing patient morbidity and trends in reimbursement are moving toward penalizing practices, which increase complications. The aim of this study was to evaluate the premise that the addition of panniculectomy to gynecologic surgery in the obese and morbidly obese patient population results in a statistically significant improvement in measureable outcomes. METHODS/RESULTS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed to assess the association of complications with panniculectomy combined with gynecologic surgery in the morbidly obese patient population. The query identified 296 patients with a body mass index greater than 30 who had panniculectomy concomitant with gynecologic surgery. The results demonstrated a statistically significant relationship (P < 0.05) of these concomitant procedures with superficial infection, wound infection, pulmonary embolism, systemic sepsis, return to operating room, length of operation and length of stay. A systematic review of the literature was then performed which identified only 5 studies that included comparative cohorts of those with gynecologic surgery, with and without panniculectomy. There was no significant benefit across the studies in measured paramters. CONCLUSION(S): This NSQIP study and systematic review of the existing literature does not support the premise that there is a statistically significant benefit associated with performing panniculectomy in conjunction with gynecologic surgery in the morbidly obese patient population. The NSQIP data demonstrate significant elevation of negative outcomes in morbidly obese patients undergoing combined procedures. In the light of the risks to patients and current direction of medical practice the addition of elective panniculectomy to gynecologic surgery should be reevaluated in the a patient population with a body mass index greater than 30.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Nagao, S. (2023). "[Ⅳ. Revival of Intraperitoneal Chemotherapy for Advanced Epithelial Ovarian Cancer]." Gan to kagaku ryoho. Cancer & chemotherapy 50(2): 171-175.
	
Nagao, S., et al. (2023). "Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial." NEJM Evidence 2(5): 1‐12.
	
Nager, C. W., et al. (2021). "Effect of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension on treatment failure in women with uterovaginal prolapse: 5-year results of a randomized clinical trial." American Journal of Obstetrics and Gynecology 225(2): 153.e151-153.e131.
	BACKGROUND: Vaginal hysterectomy with suture apical suspension is commonly performed for uterovaginal prolapse. Sacrospinous hysteropexy with graft (vaginal mesh hysteropexy) is an alternative, although in 2019 the Food and Drug Administration removed this mesh product from the United States market. OBJECTIVE: Our objective was to compare the efficacy and adverse events of these 2 procedures. STUDY DESIGN: At 9 clinical sites in the United States National Institutes of Health and National Institute of Child Health and Human Development Pelvic Floor Disorders Network, 183 postmenopausal women requesting vaginal surgery for symptomatic uterovaginal prolapse were enrolled in a multisite randomized superiority clinical trial, comparing a sacrospinous hysteropexy with graft (hysteropexy) with a vaginal hysterectomy with uterosacral ligament suspension (hysterectomy). Participants consented to remain masked to treatment assignment for the study duration. Study visits were conducted at 6-month intervals through 60 months. The primary treatment failure composite outcome (retreatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with survival modeling. Secondary outcomes included complications or adverse events, individual anatomic measures of the pelvic organ prolapse quantification examination, and presence, severity, and impact and bother of prolapse, urinary, bowel, and pain symptoms as measured by validated questionnaires. The 3-year published results suggested better primary outcomes with sacrospinous hysteropexy with graft, but the differences were not statistically significant (P=.06). This study reports the 5-year outcomes. RESULTS: A total of 183 women with a mean age of 66 years were randomized between April 2013 and February 2015; 93 were randomized to hysteropexy and 90 were randomized to hysterectomy. Notably, 175 were included in the trial, and 156 (89%) completed the 5-year follow-up. The primary outcome showed fewer failures for hysteropexy than hysterectomy through 5 years (adjusted hazard ratio, 0.58; 95% confidence interval, 0.36-0.94; P=.03), with failure rates of 37% vs 54%, respectively, resulting in a difference of -18% (95% confidence interval, -33% to -3%) at 5 years. With the exception of the Urogenital Distress Inventory, no group differences were demonstrated in patient-reported pelvic floor symptoms, prolapse symptoms, bowel function symptoms, general quality of life, body image, or pelvic pain. At their last visit through 5 years, 70% of participants (129 of 183) reported they remained masked to their treatment with no difference in masking between groups. Adverse events for hysteropexy vs hysterectomy included mesh exposure (8% vs 0%), granulation tissue after 12 weeks (1% vs 12%), and suture exposure after 12 weeks (3% vs 21%), respectively. CONCLUSION: Among women with symptomatic uterovaginal prolapse undergoing vaginal surgery, sacrospinous hysteropexy with graft resulted in a lower composite failure rate than vaginal hysterectomy through 5 years. There were no meaningful differences in patient-reported outcomes between groups. Our results suggest that this vaginal mesh hysteropexy procedure should be made available to patients.

Naghshineh, E., et al. (2022). "Intrauterine Instillation of Human Chorionic Gonadotropin with Intrauterine Insemination Catheter Around the Golden Time of Embryo Transfer Does Not Improve In Vitro Fertilization /Intracytoplasmic Sperm Injection Outcomes in Infertile Women: A Randomized Controlled Trial." Reports of biochemistry & molecular biology 11(2): 358-366.
	BACKGROUND: We set out to explore the effect of intrauterine human chorionic gonadotropin (hCG) instillation by intrauterine insemination (IUI) catheter before embryo transfer (ET) on assisted reproductive technologies (ART) outcomes of infertile women. METHODS: One hundred women with infertility who were scheduled for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included in the study. They were randomly devoted to two groups: experimental (n= 50) and control (n= 50). In the experimental group, 500 IU hCG passed into the internal cervical orifice via IUI catheter within 15 minutes before the transfer of fresh or vitrified cleavage-stage embryos. The control group underwent the same ET procedure without prior injection of hCG. RESULTS: None of the outcomes showed a statistically significant difference between the two groups. In the intervention and control groups, respectively, biochemical pregnancies rates were 26% and 18%, implantation rates were 13.5% and 8.6%, clinical pregnancies rates were 22% and 14%, ongoing pregnancies rates were 18% and 14%, and live birth rates were 14% and 12%. CONCLUSION: Intrauterine injection of hCG via IUI catheter is not recommended in a clinical routine setting at this stage. Future efforts are warranted to further refine the applicability of this modality.

Naghshineh, E., et al. (2023). "Comparison of Follicular-Phase versus Luteal- Phase Endometrial Scratching on the Success of Intrauterine Insemination (IUI): a Randomized Controlled Trial." Iranian Journal of Medical Sciences 48(1): 158.
	Background: Endometrial scratching can lead to a dramatic rise in blastocyst implantation success rate. However, the appropriate time for performing endometrial scratching during the menstrual cycle is a controversial unresolved matter. In this study, the effect of endometrial scratching on IUI success was compared in two follicular and luteal phases in infertile women who have been treated with IUI. Methods: A total of 75 infertile women were included in the study. Patients were randomly divided into three groups (n=25 per group). Group I consisted of patients who underwent endometrial scratching between days 19‐24 of the menstrual cycle in the luteal phase. Group II included women who received the same treatment on the 8th day of the menstrual cycle in the follicular phase. The patients in group III did not receive any endometrial scratching treatment before IUI. Results: No significant difference was found between the three groups in terms of age, BMI, duration of infertility, infertility type, and baseline hormone levels (P>0.05). The clinical pregnancy rate, concept moreover, there were statistically significant differences among the three groups based on the Chi‐square test results (P<0.05). In addition, Fisher's exact test did not show any differences between the three groups in terms of abortion and EP (P>0.05). Conclusion: We concluded that the follicular phase was the most appropriate time to perform endometrial scratching, and it could improve the pregnancy rate in IUI.

Nagpal, A., et al. (2021). "The Effectiveness of Dorsal Root Ganglion Neurostimulation for the Treatment of Chronic Pelvic Pain and Chronic Neuropathic Pain of the Lower Extremity: A Comprehensive Review of the Published Data." Pain medicine (Malden, Mass.) 22(1): 49-59.
	Objective: To evaluate the effectiveness of dorsal root ganglion neurostimulation for the treatment of refractory, focal pain in the pelvis and lower extremities.; Design: Systematic review.; Outcome Measures: The primary outcome was ≥50% pain relief. Secondary outcomes were physical function, mood, quality of life, opioid usage, and complications.; Results: One pragmatic randomized controlled trial, four prospective cohort studies, and eight case series met the inclusion criteria. A worst-case scenario analysis from the randomized controlled trial reported ≥50% pain relief in 74% of patients with dorsal root ganglion neurostimulation vs. 51% of patients who experienced at least 50% relief with spinal cord stimulation at 3 months. Cohort data success rates ranged from 43% to 83% at ≤6 months and 27% to 100% at >6 months. Significant improvements were also reported in the secondary outcomes assessed, including mood, quality of life, opioid usage, and health care utilization, though a lack of available quantitative data limits further statistical analysis. Complication rates vary, though the only randomized controlled trial reported a higher rate of adverse events than that seen with traditional neurostimulation.; Conclusions: In accordance with the Grades of Recommendation, Assessment, Development, and Evaluation system, low-quality evidence supports dorsal root ganglion neurostimulation as a more effective treatment than traditional neurostimulation for pain and dysfunction associated with complex regional pain syndrome or causalgia. Very low-quality evidence supports dorsal root ganglion neurostimulation for the treatment of chronic pelvic pain, chronic neuropathic groin pain, phantom limb pain, chronic neuropathic pain of the trunk and/or limbs, and diabetic neuropathy. (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nahidi, F., et al. (2021). "The effectiveness of lifestyle training program promoting adolescent health with polycystic ovarian syndrome: A study protocol for a randomized controlled study." Journal of education and health promotion 10: 351.
	Background: Lifestyle training is of a key important in adolescent age for better life in the future. Healthy lifestyle in adolescents can management of any disease such as diabetes and polycystic ovarian syndrome (PCOS). Schools can provide an important environment to identify and change the lifestyle of students. The aim of this protocol is designing and evaluating the effectiveness of school-based lifestyle training program improving the PCOS of adolescents.; Materials and Methods: A cluster-randomized controlled trial will be conducted to examine the effectiveness of school-based lifestyle training program in 16 to 18 years old adolescent girls. The healthy lifestyle program will be designed by modification of behavioral habit, dietary intake, and physical activity and educated in eight sessions for adolescents and one session for parents in the intervention groups with sixty participants.; Results: Changes in primary and secondary outcomes in PCOS and healthy adolescents before and after intervention in the intervention and control groups will be analyzed for evaluation effectiveness by one-way ANOVA or other nonparametric equivalents.; Conclusion: The current study will provide information on the effectiveness of school-based lifestyle training programs for adolescents. With increasing numbers of PCOS at risk for long-term and/or late effects of treatment and other chronic diseases, efforts for promoting the healthy lifestyle of this important group are urgently needed. This lifestyle program may provide valuable information relating to the development of other healthy lifestyle interventions for PCOS and result in appropriate behavior change and self-management strategies.; Competing Interests: There are no conflicts of interest. (Copyright: © 2021 Journal of Education and Health Promotion.)

Nahshon, C., et al. (2024). "Risk factors for pelvic organ prolapse recurrence following colpocleisis: A meta-analysis." International Journal of Gynecology and Obstetrics 164(3): 848-856.
	Background: Studies aimed to assess risk factors for pelvic organ prolapse (POP) recurrence following colpocleisis with nonconclusive results. Objective(s): To investigate risk factors for POP recurrence following colpocleisis. Search Strategy: MEDLINE, PUBMED, Embase, Web of Science, and Cochrane databases were systematically searched. Selection Criteria: Experimental and non-experimental studies investigating POP recurrence following colpocleisis. Data Collection and Analysis: We assessed the association between preoperative and postoperative physical examination findings, demographics and medical history, and the risk of recurrence following colpocleisis. Main Result(s): A total of 954 studies were identified, of which five studies comprising 2978 patients were eligible for analysis. Both preoperative and postoperative genital hiatus length were significantly longer in the recurrence group (mean difference [MD] 0.48, 95% confidence interval [CI] 0.01-0.94, P = 0.04, I2 = 0% and MD 1.15, 95% CI 0.50-1.81, P = 0.005, I2 = 0%; respectively). Preoperative total vaginal length (TVL) did not differ between groups (MD 0.05, 95% CI -0.40 to 0.50, P = 0.83, I2 = 6%), postoperative TVL was found significantly longer in the recurrence group (MD 0.07, 95% CI -0.03 to 1.38, P = 0.04, I2 = 68%). Both preoperative and postoperative perineal body did not differ between groups. Women with a previous POP surgery were more likely to experience recurrence following colpocleisis (relative risk 2.09, 95% CI 1.18-3.69, P = 0.01, I2 = 0%). Patient's age and previous hysterectomy did not affect recurrence rates. Conclusion(s): Wider preoperative and postoperative genital hiatus as well as longer post-operative TVL and previous POP surgery were associated with a higher risk for recurrence following colpocleisis, highlighting the importance of appropriate patient selection and surgical technique in minimizing this risk.Copyright © 2023 International Federation of Gynecology and Obstetrics.

Naimi, A. I., et al. (2021). "The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin-Detected Pregnancy, Pregnancy Loss, and Live Birth : per Protocol Analysis of a Randomized Trial." Annals of Internal Medicine 174(5): 595‐601.
	BACKGROUND: A previous large randomized trial indicated that preconception‐initiated low‐dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention‐to��treat approach. OBJECTIVE: To estimate per protocol effects of preconception‐initiated LDA on pregnancy loss and live birth. DESIGN: The EAGeR (Effects of Aspirin on Gestation and Reproduction) trial was used to construct a prospective cohort for a post hoc analysis. (ClinicalTrials.gov: NCT00467363). SETTING: 4 university medical centers in the United States. PARTICIPANTS: 1227 women between the ages of 18 and 40 years who had 1 or 2 previous pregnancy losses and were attempting pregnancy. MEASUREMENTS: Adherence to LDA or placebo, assessed by measuring pill bottle weights at regular intervals during follow‐up. Primary outcomes were human chorionic gonadotropin (hCG)‐detected pregnancies, pregnancy losses, and live births, determined by pregnancy tests and medical records. RESULTS: Relative to placebo, adhering to LDA for 5 of 7 days per week led to 8 more hCG‐detected pregnancies (95% CI, 4.64 to 10.96 pregnancies), 15 more live births (CI, 7.65 to 21.15 births), and 6 fewer pregnancy losses (CI, ‐12.00 to ‐0.20 losses) for every 100 women in the trial. In addition, compared with placebo, postconception initiation of LDA therapy led to a reduction in the estimated effects. Furthermore, effects were obtained in a minimum of 4 of 7 days per week. LIMITATION: The EAGeR trial data for this study were analyzed as observational data, thus are subject to the limitations of prospective observational studies. CONCLUSION: Per protocol results suggest that preconception use of LDA at least 4 days per week may improve reproductive outcomes for women who have had 1 or 2 pregnancy losses. Increasing adherence to daily LDA seems to be key to improving effectiveness. PRIMARY FUNDING SOURCE: National Institutes of Health.

Nair, D. B., et al. (2024). "Autologous Fascial Slings for Stress Urinary Incontinence: a 17-year Follow-up of a Randomised Controlled Study." International Urogynecology Journal.
	Introduction and hypothesis: Safety concerns with the use of mesh in vaginal surgery have been ongoing. Autologous fascial slings (AFS) avoid foreign body complications. We compared the long-term (17-year) outcomes of two AFS repair methods-the standard sling and short sling (sling-on-string), and assessed durability and patient satisfaction of these for the treatment of stress urinary incontinence (SUI). Method(s): A total of 107 patients from three urogynaecology units who had participated in a randomised controlled trial assessing standard (n = 52) and short (n = 55) slings were followed up for a median period of 17 years. Primary outcomes were Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores to assess the impact on the quality of life and symptom distress. Logistic quantile regression was employed to compare the two methods. Secondary outcomes included long-term complications and patient satisfaction. Result(s): Mean scores showed no statistically significant difference between the standard and short slings at the 17-year follow-up relating to IIQ and UDI scores, leakage or urgency (p > 0.05). Improved bladder function was observed at 17 years compared with baseline (standard sling-IIQ scores mean difference [MD] 1.22 [CI: 0.69, 1.74], UDI scores MD 0.83 [CI: 0.70, 0.97]; short sling-IIQ score MD 1.14 [CI: 0.73, 1.54], UDI scores MD 0.54 [CI: 0.40, 0.67]) with age-related deterioration over time. Re-operation rates were low and patient satisfaction rates were high (67.2%) at follow-up. Conclusion(s): Autologous fascial slings are an effective and durable option for management of SUI and the short sling procedure can be recommended owing to plausible surgical advantages.Copyright © 2024, The International Urogynecological Association.

Naito, Y., et al. (2023). "Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors." International Journal of Clinical Oncology 28(7): 827-840.
	Background: Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the 'Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)'. Method(s): Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. Result(s): The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. Conclusion(s): The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.Copyright © 2023, The Author(s).

Najaf, N., et al. (2021). "The Effect of Aromatherapy Alone or in Combination with Massage on Dysmenorrhea: A Systematic Review and Meta-analysis." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 43(12): 968-979.
	Objective: The aim of the present systematic review meta-analysis is to assess the effect of olfactory stimulation on reducing dysmenorrhea. METHODS: Systematic search was conducted in several databases, such as PubMed, Web of Science, Cochrane, and Scopus, to identify relevant research up to October 26, 2019. The identified studies were evaluated based on a modified Jadad scale. The intervention involves aromatherapy alone or in combination with essential oils. There was no restriction for the control group such as a placebo group or other common treatments. The Comprehensive Meta-Analysis Version 2 (Bio stat, Englewood, NJ, USA) was used for meta-analysis. Cochran's Q and I2 tests were utilized.; Results: The findings of our meta-analysis, which contained 13 trials (15 data), showed that dysmenorrhea decreased significantly in the group receiving aromatherapy with herbal compared with the control group (standardized mean difference [SMD] = -0.795; 95% confidence interval [CI]: -0.922 to- 0.667; 17 trials O < 0.001); heterogeneity; I2 = 19.47%; p = 0.236). In addition, four studies with insufficient data were not included in our meta-analysis. The results of all studies suggested that aromatherapy with herbal medicine group compared with control group is effective.; Conclusion: Aromatherapy with herbal medicine decreased dysmenorrhea. This treatment was particularly effective when aroma oil was combined with massage or when a mixture of aroma oil was used for the treatment of dysmenorrhea.; Competing Interests: The authors have no conflict of interests to declare. (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Najafabadi Maryam, S., et al. (2023). "A comparison of the portfolio low-carbohydrate diet and the ketogenic diet in overweight and obese women with polycystic ovary syndrome: study protocol for a randomized controlled trial." Trials 24(1): 509.
	Background: Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders among women of fertile age. Women with PCOS manifest clinical symptoms like menstrual dysfunction, hirsutism, insulin resistance, and hyperinsulinemia. As excessive amounts of insulin levels directly increase ovarian production of androgens, hyperinsulinemia and insulin resistance are considered as the pathogenesis factors of PCOS. The portfolio low-carbohydrate diet (PLCD) is a plant-based diet with 40% carbohydrates combined with five cholesterol-lowering foods and nutrients. On the other hand, the ketogenic diet (KD) is a nutritional protocol with 10% carbohydrates. The purpose of this study is to determine whether PLCD or KD is more effective in alleviating PCOS symptoms.; Methods: Forty-six overweight or obese women diagnosed with PCOS will be randomly stratified to receive either PLCD or KD for 8 weeks. Measures related to anthropometric and body composition, glucose, and insulin level, HOMA-IR, sex hormones, lipid profile, quality of life, dietary intake, physical activity, and Ferriman-Gallwey score of all participants will be accessed before and after the intervention.; Discussion: Since the first line treatment of PCOS is lifestyle adjustment including diet control and exercise, there has not been determined the optimal diet for this population of women yet. Hence, the goal of conducting this study is to determine whether the PLCD or the KD could have more advantageous effects on attenuating PCOS manifestations. The result of this investigation will give us new insight into curing this disease and will provide evidence-based recommendations for prescribing an optimal diet for PCOS women.; Trial Registration: IRCT20200912048693N3, Trial registered 2022-12-14. https://www.irct.ir/trial/67548. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Najjarzadeh, M., et al. (2019). "Comparison of the effect of hyaluronic acid and estrogen on atrophic vaginitis in menopausal women: A systematic review." Post Reproductive Health 25(2): 100-108.
	
Najmi, Z., et al. (2023). "Efficacy of Ibuprofen Lysine on First-Trimester AbortionRelated Pain and Hemorrhage: a Randomized TripleBlinded Clinical Trial." Archives of Iranian medicine 26(4): 212‐217.
	BACKGROUND: Some recent trials have reported high efficacy for nonsteroidal anti‐inflammatory drugs (NSAIDs) in relieving medical abortion‐related pain. The aim of this study was to determine the beneficial effect of oral NSAIDs (ibuprofen lysine) in reduction of pain and hemorrhage in first‐trimester medical abortion. METHODS: This randomized triple‐blinded clinical trial was performed on 98 pregnant women who were candidate for medical abortion within the first‐trimester period (gestational age<12 weeks). The participants were randomly assigned to receive ibuprofen lysine (684 mg orally every 4 hours) or placebo. All patients were initially treated with misoprostol (800 µg every 3 hours). Pain intensity and rate of hemorrhage were assessed every hour up to 15 hours after receiving the first dose of misoprostol by visual analogue scaling (VAS) and pictorial blood loss assessment chart (PBAC), respectively. RESULTS: Assessing the mean pain score within 15 hours of receiving misoprostol showed significantly lower pain intensity within the first 10 hours of assessment in the group receiving NSAID in comparison with the control group (P<0.001). The bleeding rate was also significantly lower in the NSAID group at the fifth (P=0.013) and ninth (P=0.040) hour of receiving misoprostol compared to the control group. We found no difference in abortion‐related complication rate between the NSAID and placebo groups (8.3% versus 8.0%, P=0.952). CONCLUSION: The use of NSAIDs (ibuprofen lysine) is a good pharmacological analgesic option for relieving medical abortionrelated pain and hemorrhage.

Nakai, K., et al. (2021). "Preliminary evaluation of the short-term outcomes of polytetrafluoroethylene mesh for pelvic organ prolapse." The Journal of Obstetrics and Gynaecology Research 47(7): 2529-2536.
	AIM: Tension-free vaginal mesh (TVM) surgery using synthetic polypropylene (PP) soft mesh had spread rapidly. However, the frequency of mesh-related postoperative complications had increased, and PP was banned in April 2019. In Japan, however, transvaginal surgery using polytetrafluoroethylene (PTFE) mesh had been approved. In this study, we evaluated the clinical outcome and quality of life (QOL) of the postoperative course using PP mesh and PTFE mesh (named "ORIHIME™" ) in a combination surgery for utero-sacral ligament suspension and anterior vaginal support using anterior TVM. METHODS: The vaginal hysterectomy and utero-sacral ligament colpopexy augmented by anterior vaginal mesh implants using PP mesh and PTFE mesh were performed on patients with stage III to IV cystocele and uterine prolapse. The clinical outcome and QOL changes in their postoperative course were evaluated by comparing 15 cases of PP mesh and 13 cases of PTFE mesh. RESULTS: There was no difference between the PP group and PTFE group in characteristics. No mesh-related complications occurred during the follow-up period. With regard to the pelvic organ prolapse quantification (POP-Q) score, no significant difference was found between the two groups. Comparing the postoperative QOL of both groups, the PTFE group had significantly higher values in two domains than PP group (SF-12v2 questionnaire). CONCLUSIONS: We used the world's first PTFE mesh to compare PP mesh with postoperative POP-Q and QOL after the same surgery, with the same operator, and at the same institution. The results showed no significant difference between both mesh materials in the short-term.

Nakamoto, R., et al. (2023). "Investigation of the Effect of Hormonal Therapy on Endometrial FDG Uptake in Postmenopausal Women." European Journal of Nuclear Medicine and Molecular Imaging 50(Supplement 1): S554-S555.
	Aim/Introduction: Hormone replacement therapy (HRT) with estrogen for women suffering from menopause has been reported to be associated with a significantly increased endometrial thickness, compared with the thickness in control subjects, when assessed sonographically. However, the effect of hormonal therapy on FDG uptake in the endometrium has not been fully investigated. In this study, we examined the effect of hormone therapy, especially HRT, on FDG uptake in the endometrium of postmenopausal women. Material(s) and Method(s): Postmenopausal women (no history of gynecological malignancies) aged 45 years and older receiving HRT or tamoxifen for breast cancer treatment (antitumoral hormonal therapy, AHT) who underwent PET/CT screening between June 2016 and April 2023 at our institution were enrolled (HT group). Menopausal status was determined by interview and/or blood data (E2<5pg/ ml, FSH>40mIU/ml). As a control group, women not receiving hormonal therapy who had undergone PET/CT screening within 5 years after menopause were enrolled. The endometrial uptake (SUVmax) and 4 levels of the visual score for endometrial uptake (4: significant uptake, 3: recognizable, 2: somehow recognizable, 1: unrecognizable) in both groups were compared. The relationship between endometrial uptake and duration (months) of HRT was examined. Result(s): There was a significant difference in FDG uptake of the endometrium between the HT and Control groups (median SUVmax: 2.3 vs 1.9, P = 0.0021) (median Visual score: 2 vs 1, P < 0.0001). In the HT group, FDG uptake in the endometrium was higher in women receiving HRT (n=14) than in women receiving AHT (n=7) (median SUVmax: 2.45 vs 1.9, P = 0.0362) (median Visual score: 3 vs 1, P = 0.0226). A significant correlation was found between endometrial uptake and duration of HRT (rho = 0.55, P = 0.042). Five women on HRT had high endometrial uptake (range of SUVmax, 3.7-9) (Visual score 4), one of whom was found to have endometrial thickening sonographically and no abnormality on histological examination, while another had increased endometrial uptake on PET/CT screening the following year (SUVmax, 3.7->11.9) and subsequent endometrial histology revealed endometrial cancer. Conclusion(s): There was a trend toward higher FDG uptake in the endometrium of postmenopausal women on HRT for longer periods. We might be careful with the increased endometrial uptake during HRT with estrogen, which contributes to the development of endometrial cancer.

Nam, S. H., et al. (2023). "Safety and Tolerability of Weekly Genexol-PM, a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel, with Carboplatin in Gynecologic Cancer: A Phase I Study." Cancer research and treatment 55(4): 1346-1354.
	Purpose This phase I study was conducted to determine the maximum tolerated dose and the recommended phase II dose of weekly administered Genexol-PM combined with carboplatin in patients with gynecologic cancer. Materials and Methods This open-label, phase I, dose-escalation study of weekly Genexol-PM included 18 patients with gynecologic cancer, who were equally divided into three cohorts of dose levels. Cohort 1 received 100 mg/m2 Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m2 Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m2 Genexol-PM and 6 AUC carboplatin. The safety and efficacy of each dose were analyzed for each cohort. Results Of the 18 patients, 11 patients were newly diagnosed and seven patients were recurrent cases. No dose-limiting toxicity was observed. The maximum tolerated dose was not defined, but a dose up to 120 mg/m2 of Genexol-PM in combination with AUC 5-6 of carboplatin could be recommended for a phase II study. In this intention-to-treat population, five patients dropped out of the study (carboplatin-related hypersensitivity, n=1; refusal of consent, n=4). Most patients (88.9%) with adverse events recovered without sequelae, and no treatment-related death occurred. The overall response rate of weekly Genexol-PM in combination with carboplatin was 72.2%. Conclusion Weekly administered Genexol-PM with carboplatin demonstrated an acceptable safety profile in gynecologic cancer patients. The recommended phase II dose of weekly Genexol-PM is up to 120 mg/m2 when combined with carboplatin.Copyright © 2023 Korean Cancer Association. All rights reserved.

nana, m., et al. (2022). "Effect of preconception intervention on pregnancy outcome in obese/overweight women undergoing IVF/ICSI - a systematic review and meta-analysis."
	
Nana, M., et al. (2021). "Oral immunosuppressants improve pregnancy outcomes in women with recurrent miscarriages: a meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Nancarrow, L., et al. (2023). "Four-dimensional ultrasound guided embryo transfers improve live birth rates when compared to the clinical touch technique: a randomised controlled trial." Scientific Reports 13(1): 14875.
	Most aspects of in-vitro fertilisation (IVF) have changed dramatically since introduction, but embryo transfer (ET) technique remains largely unaltered. We aimed to determine whether four-dimensional ultrasound guided embryo transfers (4D UGET) could improve pregnancy rates when compared with clinical touch technique (CTT). This was a single centre open labelled randomised controlled trial in a tertiary fertility centre in the UK. 320 women were randomised on the day of single ET. The primary outcome was clinical pregnancy rate (CPR), secondary outcomes included live birth rate (LBR), biochemical pregnancy rate (BPR), miscarriage, pregnancy of unknown location (PUL) and ectopic pregnancy. 4D-UGET resulted in significantly higher CPR [50% vs 36% p = 0.02, OR 1.78 (1.12-2.84)] and LBR [41% vs 28%, p = 0.02, OR 1.77 (1.09-2.87)] when compared to CTT technique. Miscarriage (p = 0.49), PUL (p = 0.14) and ectopic pregnancy (p = 0.96) were similar between the two groups. LBR, from this trial, are significantly higher than the current UK average (41% vs 24%). 4D UGET allows for superior imaging of the uterine cavity, whilst tailoring the embryo deposition point specifically to the patient. Further RCTs are required to determine if these results can be replicated in other units and whether 4D UGET is superior to 2D UGET. (© 2023. Springer Nature Limited.)

Nancarrow, L., et al. (2021). "4D-ultrasound guided embryo transfers improve live birth rates: a randomised controlled trial." BJOG 128(SUPPL 2): 232.
	Objective To determine if 4D ultrasound guided embryo transfers (4DUS) improve live birth rates (LBR) in comparison to the clinical touch technique (CTT). Study design This was a prospective, open labelled randomised controlled trial comparing superiority between two techniques for embryo transfer (ET) (4DUS versus CTT). A total of 320 (n = 160/group) patients were recruited using computer generated randomisation that were centrally distributed in consecutive sealed opaque envelopes between July 2018 to December 2019. Main outcomes were clinical pregnancy rate (CPR) and LBR. Following the procedure, participants completed a survey based on their comfort and satisfaction. Methods Inclusion criteria included single blastocyst transfer and a normal uterine cavity. Participants were recruited and randomized on the day of ET. Those allocated to the CTT group, had their embryo transferred without ultrasound, depositing the embryo 6 cm from the external os. Those in the 4DUS group had their ET using transvaginal 4D ultrasonography and had their embryos deposited at the maximal implantation point (MIP). Results Results were available from a total of 295 women (8% attrition rate, CTT n = 153; 4DUS n = 142)). No demographic differences between the two groups (CTT and 4DUS) were noted including age (P = 0.05), BMI (P = 0.29), duration of infertility (P = 0.94), type of infertility (P = 0.68) or embryo quality (P = 0.89). All the 4DUS and 95% of the CTT group were performed by the same practitioner. The 4DUS resulted in significantly higher CPR (50% versus 36% P = 0.015, OR 1.78 (1.12‐2.84)) and LBR (41% versus 28%, P = 0.021, OR 1.77 (1.09‐2.87)). There were no statistically significant differences between miscarriage (P = 0.494), pregnancy of unknown location (P = 0.141) or ectopic pregnancy rates (P = 0.958) between the two groups. The 4DUS process took significantly longer time compared with the CTT procedure (15.7 versus 10.2 min respectively, P < 0.01). The results of the survey showed no statistical difference between patient comfort (P = 0.17) or satisfaction (P = 0.08) between the groups however there were significantly more positive comments in the 4DUS (P < 0.01). In the 4DUS group there was no difference in mean endometrial thickness (P = 0.186) or endometrial volume (P = 0.836) between pregnant and non‐pregnant patients. Conclusion LBRs, in this trial utilizing 4DUS, are significantly higher than the current UK average (41% versus 22‐23%) and significantly higher than CTT. 4DUS allows for superior imaging of the uterine cavity, tailoring the embryo deposition point specifically to the patient. Further RCTs are required to confirm that 4DUS is the superior technique for ET.

Nanda, R., et al. (2023). "Ten years survival results of randomized study comparing weekly vs . triweekly cisplatin with concurrent radiation in locally advanced carcinoma cervix." Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology 28(3): 322-331.
	Background: The current standard of treatment for locally advanced cervical cancer is concurrent chemo-radiation with improved overall survival (OS) by 6% with manageable toxicities. The cisplatin 40 mg/m 2 given weekly is the widely practiced regimen for 4-6 cycles concurrently with irradiation.; Materials and Methods: Two hundred and twelve patients with histologically proven squamous cell carcinoma of cervix with stages IIB to IIIB were enrolled between 2007-2011. External beam radiation dose of 45 Gy in 25 fractions was delivered over 5 weeks. Brachytherapy was delivered by manual afterloading cesium-137 (Cs137) low dose brachytherapy (LDR) using modified Fletcher suit intracavitary applicators to a total dose of 30 Gy to Point A or interstitial template to dose of 21 Gy/3 fractions with remote afterloading iridium-192 (Ir192) high dose brachytherapy (HDR). Patients were randomized to arm A receiving 40 mg/m 2 of concurrent cisplatin weekly and arm B receiving 100 mg/m 2 of concurrent cisplatin triweekly.; Results: One hundred and nine patients were randomized to weekly cisplatin and one hundred and three patients to triweekly cisplatin at the end of recruitment. At ten years, the OS was higher in the weekly arm (79.8%) compared to triweekly arm (70.9%). Disease free survival (DFS) was almost equal (76.1% and 73.8%) in the weekly and three-weekly arms. There is definite significance in overall DFS with patients receiving the cumulative cisplatin doses of more than 250 mg (p = 0.028). The patients with more than 45 years of age had better overall survival (OS) (79%) with statistical significance 31 (p = 0.020).; Conclusion: Both cisplatin based triweekly and weekly concurrent chemotherapy are equally effective in terms of OS and DFS.; Competing Interests: Conflicts of interest None declared. (© 2023 Greater Poland Cancer Centre.)

Nankali, A., et al. (2020). "The effect of unilateral and bilateral laparoscopic surgery for endometriosis on Anti-Mullerian Hormone (AMH) level after 3 and 6 months: a systematic review and meta-analysis." Health and quality of life outcomes 18(1): 314.
	Background: Endometriosis is one of the most common causes of infertility. The causes of the disease and its definitive treatments are still unclear. Moreover, Anti-Mullerian Hormone (AMH) is a glycoprotein dimer that is a member of the transient growth factors family. This research work aimed to identify the effect of unilateral and bilateral laparoscopic surgery for endometriosis on AMH levels after 3 months, and 6 months, using meta-analysis.; Methods: In this study, the articles published in national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, Science Direct, Scopus, PubMed, and Web of Science (ISI) were searched to find electronically published studies between 2010 and 2019. The heterogeneous index between studies was determined using the I 2 index.; Results: In this meta-analysis and systematic review, 19 articles were eligible for inclusion in the study. The standardized mean difference was obtained in examining of unilateral laparoscopic surgery for endometriosis (before intervention 2.8 ± 0.11, and after 3 months 2.05 ± 0.13; and before intervention 3.1 ± 0.46 and after 6 months 2.08 ± 0.31), and in examining bilateral laparoscopic surgery for endometriosis examination (before intervention 2.0 ± 08.08, and after 3 months 1.1 ± 0.1; and before intervention 2.9 ± 0.23 and after 6 months 1.4 ± 0.19).; Conclusion: The results of this study demonstrate that unilateral and bilateral laparoscopic surgery for endometriosis is effective on AMH levels, and the level decreases in both comparisons.

Naotaka, S., et al. (2021). "Efficacy of estrogen-progestin combination pills and progestin-only pills on Dysmenorrhea: A systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Nappi, R. E., et al. (2023). "Treatment of moderate-to-severe vasomotor symptoms associated with menopause with fezolinetant: pooled responder analysis from SKYLIGHT 1 and 2." Maturitas 173: 75.
	Context: SKYLIGHT 1 and 2 (NCT04003155, NCT04003142) were identical, double-blind, placebo-controlled phase 3 studies evaluating the safety and efficacy of fezolinetant (a nonhormonal selective neurokinin-3 receptor antagonist) on frequency and severity of vasomotor symptoms (VMS) associated with menopause. Fezolinetant was efficacious, safe and well tolerated in both studies. Objective(s): Assess response to fezolinetant via a prespecified analysis using pooled data from SKYLIGHT 1 and 2. Method(s): Women >=40-<=65y with moderate-to-severe VMS (average >=7 hot flashes/day) took once-daily placebo or fezolinetant 30mg or 45mg for 12 weeks. Main Outcome Measure(s): Percentages of women with reductions in frequency of moderate and severe VMS of >=50% and >=75% from baseline up to week 12; percentages who achieved clinically meaningful responses on combinations of one, two or three outcome measures at week 12 (VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form [PROMIS SD SF] 8b Total Score, Menopause-Specific Quality of Life [MENQOL] Total Score and MENQOL VMS Domain Score). Result(s): 1022 women took >=1 dose (placebo n=342, fezolinetant 30mg n=339, fezolinetant 45mg n=341). At week 12, 36% and 17% of placebo, 48% and 32% of fezolinetant 30mg and 59% and 37% of fezolinetant 45mg groups had a >=50% or >=75% reduction from baseline in VMS frequency, respectively. The odds ratios for the percentages with >=50% and >=75% reductions vs placebo were statistically significant for both fezolinetant doses (weeks 1-12). Overall, 31% (88/280) of placebo, 50% (133/266) of fezolinetant 30mg and 55% (161/292) of fezolinetant 45mg groups achieved a clinically meaningful reduction in VMS frequency. The odds ratios were statistically significant vs placebo for both fezolinetant doses for the percentages of women who were double responders on: 1) VMS frequency and PROMIS SD SF 8b Total Score, 2) VMS frequency and MENQOL Total Score and 3) VMS frequency and MENQOL VMS Domain Score. The odds ratios were statistically significant for both fezolinetant doses vs placebo for the percentages of women who were triple responders on 1) VMS frequency, PROMIS SD SF 8b Total Score and MENQOL Total Score and 2) VMS frequency, PROMIS SD SF 8b Total Score and MENQOL VMS Domain Score. Conclusion(s): These pooled data from SKYLIGHT 1 and 2 show a clinically meaningful benefit with fezolinetant using combinations of objective and patient reported outcome measures.Copyright © 2023

Narayanamoorthy, S., et al. (2023). "Incarcerated gravid uterus - A systematic review." European Journal of Obstetrics & Gynecology and Reproductive Biology: X 19: 100227.
	Incarcerated gravid uterus (IGU) is a serious complication of pregnancy that leads to adverse obstetric outcomes. The aim of this review was to describe this entity in detail. We also aimed to understand if pregnancies with predisposing risk factors that increase the risk of developing IGU had a difference in their clinical manifestations, treatment, and obstetric outcomes. The PubMed, MEDLINE, Embase, Scopus databases and clinicaltrials.gov were searched from inception to July 2023. Case reports and series that provided all the details of the pregnancy and IGU outcome were included. Study quality and risk of bias were assessed using a tool that is an adaptation from criteria listed by Pierson, Bradford Hills and Newcastle Ottawa scale modification. Patients with the condition of interest included in this review were grouped into those with documented, identified risk factors and no risk factors. The two groups were compared to understand the difference in obstetric outcome and presentation of IGU. Data were analyzed and summarized descriptively, categorical variables were assessed by chi-squared test or Fisher's exact test, and continuous variables by the Wilcoxon Mann Whitney test. Of 236 articles found, 62 articles with 80 cases were included in the final analysis. The median age was 32 [27-35] years. The median gestational age of diagnosis was 17 [14-26] weeks. The most common risk factor was fibroids (N = 22, 27.5 %). Most common presentation was urinary complaints and lower abdomen pain (N = 47, 58.6 %). Twenty-seven patients (33.6 %) needed more than one visit for the diagnosis to be made. Conservative management was the first step to treat IGU in most patients. Most common complication was fetal malpresentation (N = 13, 40.6 %). Patients with or without risk factors developing IGU had no statistical difference in- parity, median gestational age of diagnosis, delay in diagnosis, increased chance of misdiagnosis, management of IGU or in obstetric outcome (all p > 0.05). It is important to recognize this entity early to prevent obstetric complications especially when patients report urinary retention and abdomen pain. The presence of risk factors does not change the management course or obstetric outcome in patients with IGU. Hence it is reasonable to start with conservative management of IGU regardless of presence of risk factors or the gestational age of diagnosis, in clinical practice.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. (© 2023 The Authors.)

Naser, B., et al. (2022). "Weight gain in menopause: systematic review of adverse events in women treated with black cohosh." Climacteric : the journal of the International Menopause Society 25(3): 220-227.
	Weight gain is a frequent problem in perimenopausal and postmenopausal women. Cimicifuga racemosa (CR) is a popular treatment option for menopausal symptoms. The aim of this review was to investigate whether there is scientific evidence that CR causes weight gain. We searched our database for medically confirmed, spontaneous adverse events regarding weight gain, literature for case reports and randomized controlled trials. Thirty cases in total were spontaneously reported in 15 years. The causality was not considered certain/likely in any of the cases. A nurse (consumer) assessed the causality as possible. Only one case was published in the literature. However, no change in body fat composition was reported, and the causality seems unlikely. Of the 31 identified studies, 17 were double-blind placebo-controlled, five were double-blind reference-controlled and nine were open reference-controlled. In total, 1839 women were treated with CR for up to 12 months. Two studies reported weight gain as an adverse event; however, no significant differences in weight changes were observed between the groups. One case of weight gain (about 2 kg) was reported, but the authors did not specify in which treatment group. In conclusion, this study provides no scientific evidence that the use of Cimicifuga racemosa causes weight gain in menopausal women.

Naser, M., et al. (2022). "Usefulness of Mesh Adjustment 24 Hours after Retropubic Mesh Insertion in Patients Undergoing Stress Urinary Incontinence Surgery. A Prospective Randomized Multicenter Study." International Urogynecology Journal 33(Supplement 2): S512-S513.
	Introduction: Currently, retropubic tension-free suburethral mesh (TVT) placement is considered the first-line treatment for stress urinary incontinence (SUI). Due to regional and general anesthesia to perform urinary incontinence procedures, it is difficult to carry out an intraoperative stress test. In 2012, at the 37th IUGA Congress held in Brisbane, a study was presented that performed stress tests and mesh adjustment 24 h after the procedure in patients undergoing trans-obturator mesh, with a success rate. However, there are no data for the retropubic technique. Objective(s): The main objective is to assess the usefulness of mesh adjustment 24 h after TVT placement in patients with SUI. Method(s): A prospective multicenter randomized double-blind study was conducted. Patients from two hospital centers in Santiago de Chile were enrolled. The sample calculation was made to detect a difference of 10%, considering an error alpha<5% and an error beta<20%, one-tailed, with 20% oversampling in case lost. A stress test was performed 24 hours after the procedure in all patients who received TVT. Surgeons were blinded. Those patients who presented urine leakage in the stress test were randomized into the interventional group and the control group. For the intervention group, mesh adjustment was performed if urine leaked. In the control group, no adjustment was made. Sandvik index and stress test were measured at 3 and 12 months after surgery. Result(s): The results obtained are preliminary because the study is ongoing. A total of 32 subjects are presented, 18 in the interventional group and 14 in the control group. The analyst was blind to the data obtained. From the results found, at 3 months in the intervention group, there were 14 subjects with mild Sandvik index (14/18), 2 with moderate (2/18), 1 severe (1/18), and one without escape (1/18), while in the control group there were 12 patients with a mild Sandvik index (12/14), 1 moderate (1/14), none severe (0/14), and 1 without escape (1/14). The differences between both groups were not significant (p=0.801). In the intervention group, there were 4 who presented escape to the stress test (4/18) and 4 in the control group (4/14), not finding differences between them either (p=0.496). At 12 months post-surgery, in the intervention group, there were 15 subjects with a mild Sandvik index (15/18), 1 moderate (1/18), 2 severe (2/18), and none without escape (0/18), while in the control group there were 12 patients with mild Sandvik index (12/14), 2 moderate (2/14), none severe (0/14) and none without escape (0/14). The differences between both groups were not significant (p=0.333). In the intervention group, there were 4 who continued to escape the stress test (4/18) and 4 in the control group (4/14), with no differences being found between them (p=0.496). The test used was chi-square. Conclusion(s): The preliminary results of this study allow us to infer that there is no difference between adjusting the mesh 24h after in patients who leak urine in the stress test performed 24h after TVT in subjective or objective terms. A larger number of recruited subjects will be expected to obtain more solid conclusions.

Naser, M., et al. (2022). "USEFULNESS OF MESH ADJUSTMENT 24 HOURS AFTER RETROPUBIC MESH INSERTION IN PATIENTS UNDERGOING STRESS URINARY INCONTINENCE SURGERY. A PROSPECTIVE RANDOMIZED MULTICENTER STUDY." Female Pelvic Medicine & Reconstructive Surgery 28(6): S281.
	Introduction: Currently, retropubic tension‐free suburethral mesh (TVT) placement is considered the first‐line treatment for stress urinary incontinence (SUI). Due to regional and general anesthesia to perform urinary incontinence procedures, it is difficult to carry out an intraoperative stress test. In 2012, at the 37th IUGA Congress held in Brisbane, a study was presented that performed stress tests and mesh adjustment 24 h after the procedure in patients undergoing trans‐obturator mesh, with a success rate. However, there are no data for the retropubic technique. Objective: The main objective is to assess the usefulness of mesh adjustment 24 h after TVT placement in patients with SUI. Methods: A prospective multicenter randomized double‐blind study was conducted. Patients from two hospital centers in Santiago de Chile were enrolled. The sample calculation was made to detect a difference of 10%, considering an error α < 5% and an error β<20%, one‐tailed, with 20% oversampling in case lost. A stress test was performed 24 hours after the procedure in all patients who received TVT. Surgeons were blinded. Those patients who presented urine leakage in the stress test were randomized into the interventional group and the control group. For the intervention group, mesh adjustment was performed if urine leaked. In the control group, no adjustment was made. Sandvik index and stress test were measured at 3 and 12 months after surgery. Results: The results obtained are preliminary because the study is ongoing. A total of 32 subjects are presented, 18 in the interventional group and 14 in the control group. The analyst was blind to the data obtained. From the results found, at 3 months in the intervention group, there were 14 subjects with mild Sandvik index (14/18), 2 with moderate (2/18), 1 severe (1/18), and one without escape (1/18), while in the control group there were 12 patients with a mild Sandvik index (12/14), 1 moderate (1/14), none severe (0/14), and 1 without escape (1/14). The differences between both groups were not significant (P = 0.801). In the intervention group, there were 4 who presented escape to the stress test (4/18) and 4 in the control group (4/14), not finding differences between them either (P = 0.496). At 12 months post‐surgery, in the intervention group, there were 15 subjects with a mild Sandvik index (15/18), 1 moderate (1/18), 2 severe (2/18), and none without escape (0/18), while in the control group there were 12 patients with mild Sandvik index (12/14), 2 moderate (2/14), none severe (0/14) and none without escape (0/14). The differences between both groups were not significant (P = 0.333). In the intervention group, there were 4 who continued to escape the stress test (4/18) and 4 in the control group (4/14), with no differences being found between them (P = 0.496). The test used was chi‐square. Conclusions: The preliminary results of this study allow us to infer that there is no difference between adjusting the mesh 24 h after in patients who leak urine in the stress test performed 24 h after TVT in subjective or objective terms. A larger number of recruited subjects will be expected to obtain more solid conclusions.

Nasiadek, M., et al. (2020). "The Role of Zinc in Selected Female Reproductive System Disorders." Nutrients 12(8).
	Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.

nasim, n., et al. (2021). "PTNS (posterior tibial nerve stimulation) efficacy in the treatment of lower urinary tract disorder in pediatrics: a systematic review."
	
Nasimi Doost Azgomi, R., et al. (2022). "Potential roles of genistein in polycystic ovary syndrome: A comprehensive systematic review." European Journal of Pharmacology 933: 175275.
	Polycystic ovary syndrome (PCOS) is one of the most prevalent polygenic endocrine disorders in reproductive-age women. Genistein is a soy-isolated phytoestrogen and isoflavone with antioxidant, anti-inflammatory, estrogenic, and antineoplastic activity. This systematic review aimed to investigate the therapeutic effects and mechanisms of actions of genistein in PCOS. The present study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. We searched PubMed, Scopus, Embase, and Google Scholar databases up to February 2022 using relative keywords. Studies published in English evaluated genistein's effects on PCOS, and its related symptoms were considered. Out of 298 records screened, only 13 articles met the inclusion criteria: Nine animal and 4 human studies. The results of the current study indicated that genistein supplementation may effectively improve PCOS-related symptoms by decreasing insulin resistance and anthropometric indices, improving ovarian morphology and regulating reproductive hormones, and reducing oxidative stress and inflammation by influencing biological pathways. According to the current literature, genistein may diminish the dues of PCOS. Therefore, this study shows that genistein can be considered an effective agent. in reducing the complications of PCOS. However, further studies are recommended for a broad conclusion on the exact mechanism of genistein in PCOS patients.; Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest that may influence the results. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nasiri, M., et al. (2022). "The Effect of High Intensity Intermittent and Combined (Resistant and Endurance) Trainings on Some Anthropometric Indices and Aerobic Performance in Women with Polycystic Ovary Syndrome: A Randomized Controlled Clinical Trial Study." International Journal of Fertility & Sterility 16(4): 268-274.
	Background: Overweight and obesity are associated with cardiometabolic risk in polycystic ovary syndrome (PCOS). Lifestyle adjustment, such as increasing physical activity, is a first-line strategy to treat PCOS. The current study aims to compare and examine the effect of high intensity intermittent training (HIIT) and combined (COM) training on some anthropometric indices and aerobic performance in PCOS females.; Materials and Methods: This randomized controlled clinical trial was conducted on 45 women with PCOS divided into three groups receiving HIIT (n=15), COM interventions (n=15) or control group (n=15) for eight weeks. Some anthropometric indices factors including weight, body mass index (BMI), waist to hip ratio (WHR), body fat percent (FP), and visceral adipose tissue (VAT) as well as VO2 max were measured at the baseline at the eighth week. Data were analyzed by one-way ANOVA test. Tukey post hoc tests were used to compare the pair differences.; Results: After eight-week intervention, weight, BMI, WHR, FP, and VAT decreased significantly in both groups of COM and HIIT (P<0.05) relative to the control group. There were no differences between HIIT group and COM group in terms of these variables (P>0.05). VO2 max increased significantly after COM and HIIT interventions relative to the control group (P=0.001); however, HIIT was statically more effective than COM (P=0.011).; Conclusion: The current study revealed that both HIIT and COM trainings could be beneficial in improving some anthropometric indices in addition to aerobic capacity, although HIIT was more effective on aerobic performance (registration number: IRCT20130812014333N143).

Nassif, J., et al. (2022). "Rate of Mesh Erosion After Sacrocolpopexy With Concurrent Supracervical Compared With Total Hysterectomy: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 140(3): 412-420.
	Objective: To estimate the effect of concomitant supracervical hysterectomy compared with total hysterectomy during abdominal sacrocolpopexy on the rate of mesh erosion by performing a systematic review and meta-analysis of the existing literature.; Data Sources: From database inception through January 2022, we explored MEDLINE, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov , and Cochrane Central Register of Controlled Trials. Studies comparing the rate of mesh erosion in women undergoing abdominal sacrocolpopexy who had concomitant supracervical hysterectomy compared with total hysterectomy were included.; Data Extraction and Synthesis: Two reviewers separately ascertained studies, obtained data, and gauged study quality. The rate of mesh erosion was compared, and odds ratios (ORs) with 95% CIs were estimated.; Tabulation, Integration, and Results: Nineteen studies with 10,572 women who underwent abdominal sacrocolpopexy were identified, including 4,285 women in the supracervical group and 6,287 women in the total hysterectomy group. The overall mean postprocedure follow-up time was 30.7±15.1 months (median 12.4, range 1.5-44.2). The median (95% CI) point prevalence of mesh erosion was 0.36% (0-1.9%) in women who had supracervical hysterectomy compared with 3.8% (1.8-8.7%) in women who had total hysterectomy. The overall rate of mesh erosion in women who had supracervical hysterectomy was lower compared with women who had total hysterectomy (pooled OR 0.26, 95% CI 0.18-0.38, I 2 0%).; Conclusion: In women with symptomatic apical pelvic organ prolapse who undergo abdominal sacrocolpopexy with concomitant hysterectomy, supracervical hysterectomy is associated with a lower risk of mesh erosion compared with total hysterectomy.; Systematic Review Registration: PROSPERO, CRD42022301862.; Competing Interests: Financial Disclosure Joseph Nassif disclosed money was paid to him from the Gerson Lehrman Group. The other authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Nasution, L. A. and Y. Afiyanti (2021). "Spiritual based intervention effect on the psychological aspect of patients with gynaecologic and breast cancer: A systematic review." Enfermeria clinica 31 Suppl 2: S90-S95.
	The complexity of care on patients with gynaecological and breast cancer causes various psychological effects, and therefore, spiritual-based intervention is developed to overcome these problems. The purpose of this study is to determine the effects of the spiritual-based intervention on the psychological aspect of patients with gynaecological and breast cancer. The method used to prepare this systematic review is Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). There are 14 related articles. Spiritual-based interventions in this study were conducted ranging from 4 to 8 sessions, with an average duration of about 60-90min/session. The effects of spiritual-based intervention on the psychological aspect of cancer patients include reducing anxiety and depression, improving spiritual and emotional well-being, improving coping and quality of life for patients with gynaecological and breast cancer. Spiritual-based intervention is affecting the physical condition, psychological state, and quality of life of cancer patients.

Nathalia, N. and H. Jose de la (2023). "Systematic review: Postabortion myometrial hypervascularization in the first trimester, incidence and outcomes according to treatment." PROSPERO International prospective register of systematic reviews.
	
National Cancer Center, K. (2022). HIPEC for Platinum-Resistant Recurrent Ovarian Cancer.
	No Results Available Procedure: HIPEC Progression-free survival (PFS)|Overall survival (OS)|cancer-specific survival|Treatment-related adverse events|Health-related quality of life (QLQ C30)|Health-related quality of life (QLQ OV28)|Health-related quality of life (EQ-5D-5L)|Cost-effectiveness analysis Female Phase 3 140 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NCC2021-0334 December 31, 2029

National Cancer Center, K. (2023). Interval Cytoreductive Surgery With or Without HIPEC for Ovarian Cancer (KOV-HIPEC-04).
	No Results Available Drug: Cisplatin Overall survival (OS)|Progression-free survival (PFS)|Cancer-specific survival|Time to first subsequent therapy (TFST)|Treatment-related adverse events|Health-related quality of life (EORTC-QLQ-C30)|Health-related quality of life (EORTC-QLQ-OV28)|Health-related quality of life (EQ-5D-5L)|Cost-effectiveness analysis All Phase 3 520 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment NCC2023-0100 December 31, 2030

National Cancer Institute, N. (2022). MITO 35B: Olaparib Beyond Progression Compared to Platinum Chemotherapy After Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer Patients.
	No Results Available Drug: Olaparib|Drug: Chemotherapy drug Progression-free survival (PFS)|Progession free survival 2 (PFS2)|Overall survival|Determination of changes in quality of life|Determination of changes in patient-reported outcome (PRO) symptomatic toxicities|Changes in patient-reported outcome (PRO) of cancer-related financial toxicity|Number of participants with treatment-related side effects Female Phase 3 200 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MITO35B/EudraCT:2021-000245-41 January 21, 2028

Navarro, P., et al. (2021). "Effects of ulipristal acetate in patients with symptomatic uterine fibroids." Medwave 21(4): e8162.
	Introduction: Uterine fibroids are frequently encountered in gynecology and are a therapeutic challenge. New therapies, such as ulipristal acetate, could help with symptomatic relief, improve quality of life, and decrease uterine fibroid size. Notwithstanding, there is controversy about adverse effects, especially for hepatotoxicity.; Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach.; Results and Conclusions: We identified nine systematic reviews and included ten studies overall, of which five were randomized trials. We conclude that ulipristal increases the likelihood of amenorrhea, improves the quality of life, and decreases menstrual bleeding. However, there is also a likely increase in the risk of adverse effects. Furthermore, ulipristal could decrease the size of fibroids. English full text: https://www.medwave.cl/puestadia/resepis/8162.html?lang=en

Navas, A., et al. (2021). "Effectiveness of Moderate-Intensity Aerobic Water Exercise during Pregnancy on Quality of Life and Postpartum Depression: A Multi-Center, Randomized Controlled Trial." Journal of Clinical Medicine 10(11).
	BACKGROUND: The global prevalence of postpartum depression is about 20%. This disease has serious consequences for women, their infants, and their families. The aim of this randomized clinical trial was to analyze the effectiveness and safety of a moderate-intensity aerobic water exercise program on postpartum depression, sleep problems, and quality of life in women at one month after delivery. METHODS: This was a multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. Pregnant women (14-20 weeks gestational age) who had low risk of complications and were from five primary care centers in the area covered by the obstetrics unit of Son Llatzer Hospital (Mallorca, Spain) were invited to participate. A total of 320 pregnant women were randomly assigned to two groups, an intervention group (moderate aquatic aerobic exercise) and a control group (usual prenatal care). One month after birth, sleep quality (MOS sleep), quality of life (EQ-5D), and presence of anxiety or depression (EPDS) were recorded. FINDINGS: Women in the intervention group were less likely to report anxiety or depression on the EQ5D (11.5% vs. 22.7%; p < 0.05) and had a lower mean EPDS score (6.1 ± 1.9 vs. 6.8 ± 2.4, p < 0.010). The two groups had no significant differences in other outcomes, maternal adverse events, and indicators of the newborn status. CONCLUSION: Moderate-intensity aquatic exercise during pregnancy decreased postpartum anxiety and depressive symptoms in mothers and was safe for mothers and their newborns.

Nayak, S. G., et al. (2022). "Meditation and yoga impact on dysmenorrhea (MY-ID): a study protocol." F1000Research 11.
	Primary dysmenorrhea is one of the most prevalent gynecologic condition affecting women, especially adolescent girls. Among adolescents, associated symptoms of dysmenorrhea impact the general health status, negatively influence the quality of life, resulting in school absenteeism and decreased academic performance. This study protocol was developed to estimate the prevalence of dysmenorrhea and evaluate the effectiveness of Meditation and Yoga intervention on dysmenorrhea among adolescent girls. In phase I, data will be collected from adolescent girls (N » 5000) aged between 13 and 18 years to estimate the prevalence of dysmenorrhea and in the second phase, Cluster‐Randomized Controlled Trial will be conducted to evaluate the impact of Meditation and Yoga on dysmenorrhea. From the first phase, those adolescent girls (N=400) with high pain intensity (numerical pain rating scale ≥ 4) from each school, with schools as clusters, will be assigned to the interventional and control arm. The interventional arm will receive the proposed Meditation and Yoga intervention for 12 weeks under supervision and the control arm will continue with standard routine care. The outcomes such as pain intensity, stress, academic performance, self‐efficacy and biomarker levels (Hb, Progesterone, Estrogen, Prostaglandins F2α and E2) will be assessed at baseline and 12 weeks after the intervention. Yoga's popularity and medical benefits have grown with the growing interest in alternative and complementary medicine. There is insufficient evidence to support yoga as a treatment for dysmenorrhea symptoms. This research contributes to the evidence on the impact of meditation and yoga on primary dysmenorrhea among adolescent girls.

Naz, M. S. G. and F. R. Tehrani (2020). "Effect of laser and intense pulsed light in treatment of hirsutism in women with polycystic ovary syndrome (Pcos): A systematic review." Iranian Journal of Obstetrics, Gynecology and Infertility 23(10): 96-108.
	Introduction: During recent decades, laser therapy has been one of the most popular methods in treatment of hirsutism in women with polycystic ovary syndrome (PCOS). This study was performed with aim to determine the therapeutic effect of laser on hirsutism in women with PCOS as a systematic review. Method(s): The search process of experimental and semi-experimental studies (Persian and English language) was performed in databases including PubMed, Scopus, Web of Science, Cochrane library, Magiran, SID, and IranDoc up to July 2020. The search was performed using the keywords of polycystic ovary syndrome, hirsutism, laser, treatment, hair, and the related latin keywords. The main outcomes were the effect of interventions on hair loss, hair loss duration, the duration of new hair growth, and the side effects of laser treatment. Result(s): After the advanced search, 11 articles (638 participants) had inclusion criteria. The skin type of the participants was based on Fitzpatrick scale. The majority of studies used the Alexandrite laser device. The duration of treatment in the studies was a maximum of 6 months with treatment intervals of 4 to 6 weeks. The main outcomes of this study included: significant reduction in the number of hairs and the intensity of excess hair, an increase in the mean growth time of new hair, energy levels in the range of 10 to 50 j/cm2 and duration of 20-50 milliseconds. The complications included hyperpigmentation, erythema, and pain. Conclusion(s): The findings indicated the impact of light-based technologies on different types of outcomes associated with the treatment of hirsutism in women with PCOS, but due to the limitations, there is no consensus on the most appropriate type of laser, fluorescence, and the number of treatment sessions. Greater clinical trial studies are needed to develop the clinical guidelines.Copyright © 2020, Mashhad University of Medical Sciences. All rights reserved.

Naz, M. S. G. and F. R. Tehrani (2021). "Effect of cinnamon on polycystic ovary syndrome (Pcos): A systematic review." Iranian Journal of Obstetrics, Gynecology and Infertility 23(12): 86-97.
	Introduction: The effectiveness of various medicinal plants on clinical and non-clinical symptoms of PCOS has been investigated. This study was performed with aim to determine the efficacy of cinnamon on PCOS in a systematic review. Method(s): In this systematic review study, the studies were searched in the Iranian and international databases of PubMed, Scopus, Web of science, Cochrane library, Magiran, SID, and IranDoc in February 2020. The terms of "polycystic ovary syndrome", "cinnamon" and "medicinal plant" were used for the searching process. In this study, a variety of experimental and semi-experimental human and animal studies with aim to evaluate the effect of cinnamon on PCOS were entered to the study. Result(s): In this systematic review study, 588 articles were reviewed, and finally, eight original human research articles, 1 article as an article presented in the congress, and 3 animal articles had the inclusion criteria. In terms of primary outcome, one study had reported a significant improvement in the frequency of menstrual cycles (improvement in oligomenorrhea status), six studies had reported a significant improvement in metabolic indicators, and one study had reported a decrease in Anti-mullerian hormone levels. Animal studies had reported improvement in metabolic indicators, hormonal levels, and follicle maturation. Conclusion(s): The majority of human and animal studies indicated that cinnamon consumption can be useful in improving metabolic indicators and some clinical symptoms in patients with PCOS. Therefore, more clinical trial studies are recommended to be performed for determining its efficacy and dose.Copyright © 2021, Mashhad University of Medical Sciences. All rights reserved.

Nazari Amir, M., et al. (2023). "The effect of Benson relaxation technique on cancer patients: a systematic review." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 31(12): 681.
	Purpose: Although many studies have investigated the effect of this method on cancer patients, no review of the available literature has been done. So, a literature review is conducted to evaluate all published literature on the Benson relaxation technique in cancer patients.; Methods: A systematic literature search was conducted. A systematic search of online electronic databases including PubMed/MEDLINE, Scopus Web of Science, PsycINFO, and EMBASE was performed using keywords extracted from Medical Subject Headings such as "Benson Relaxation Technique," "Cancer Patients," "Malignancy," and "Neoplasia" from the beginning to April 27, 2023. A total of 810 publications were assessed for relevance by title and abstract. The remaining 31 articles were examined using inclusion criteria for all Persian and English-language publications that evaluate the effectiveness of the Benson relaxation technique on cancer patients. We did not have gray literature in our review. The methodological quality of the included studies was appraised using specific checklists.; Results: Finally, nine studies were included in this systematic review. Studies on breast cancer patients showed improvement in fatigue, nausea, vomiting, pain, shortness of breath, insomnia, anorexia, constipation, diarrhea, treatment side effects, breast symptoms, arm symptoms, worry about hair loss, and scores of hope. Two studies were conducted among cervical cancer patients that showed a decrease in anxiety scores and an improvement in the quality of sleep. Another study on gastric cancer patients showed decreased Chemotherapy-Induced Nausea, Vomiting, and Retching scores.; Conclusion: Overall, this systematic review showed that the Benson relaxation method could improve sleep quality, appetite, anxiety, and quality of life. Therefore, using the Benson relaxation technique is suggested to improve health-related outcomes in cancer patients. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nazari, L., et al. (2022). "The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial." Reproductive sciences (Thousand Oaks, Calif.) 29(3): 993-1000.
	Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of platelet-rich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET. (© 2021. Society for Reproductive Investigation.)

Nazia, H., et al. (2021). "Is antifungal therapy along with antibiofilm agent associated with a low rate of treatment failure, resistance development and infection recurrence in non-virgin females with a biofilm-associated candidal vulvovaginitis?".
	
Nazirudeen, R., et al. (2023). "A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome." Clinical Endocrinology 99(2): 198-205.
	Objective: Insulin resistance and hyperinsulinemia plays an important role in pathogenesis of polycystic ovary syndrome (PCOS). Metformin, Myoinositol and d-chiro-inositol acts as insulin sensitizers and exerts a beneficial effects in PCOS. The objective is to compare the effect of metformin monotherapy versus a combination of metformin with Myoinositol and d-chiro-inositol in PCOS.; Design: This study is a randomized controlled trial conducted over a period of 6 months. All overweight and obese women with PCOS with the age group between 18 and 35 were included and randomized into two groups, 27 in the metformin monotherapy arm and 26 in the myoinositol combination arm.; Patients and Measurements: The variables assessed were duration of menstrual cycle, anthropometric parameters, modified Ferriman Gallwey score, global acne score, Fasting insulin, HOMA-IR, fasting lipid profile, serum testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, anti-Mullerian hormone, and pelvic ultrasound to assess ovarian volume, PCOS Questionnaire score. Changes in the parameters from baseline at the end of 6 months of treatment were assessed and compared between the groups.; Results: Menstrual cycle regularity improved in both groups with significantly greater improvement in the group receiving myoinositol-based therapy (p < .001). Pregnancy rate was equal in both the arms. There was a significant improvement in PCOSQ score in myoinositol-based therapy group (p < .001). However, there was no statistically significant difference in other hormonal, metabolic parameters between two groups in spite of symptomatic benefits.; Conclusions: The addition of myoinositol to metformin exerts additional benefits in improving menstrual cycle regularity, and quality of life in women with PCOS. (© 2023 John Wiley & Sons Ltd.)

Nazlı, A. M. and A. University (2022). The Effect of Hydrogen-rich Water on Premenstrual Symptoms and Quality of Life.
	No Results Available Other: Hydrogenated water consumption|Other: Drinking water consumption Change in premenstrual symptoms assessed by The Premenstrual Syndrome Scale|Change in quality of life assessed by World Health Organization Quality of Life Female Not Applicable 72 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Supportive Care 0720 April 28, 2023

Nct (2021). "1 Day Workshops for Preventing PPD: a Pilot Study." ClinicalTrails.gov.
	Postpartum depression affects up to 1 in 5 mothers, however just 15% receive evidence‐based treatment. It is associated with negative consequences for women and their families with enormous costs to the healthcare system. Postpartum depression is an ideal candidate for prevention because it is common, the window of opportunity to intervene is clear (pregnancy), and its risk factors are well‐established and easily identifiable. Furthermore, women are in frequent contact with the healthcare system during pregnancy and are more motivated to improve their health during this time than at any other time in their lives. Given high rates of PPD and its adverse effects on mothers and their families, and the relative lack of efficient, effective psychotherapeutic interventions for preventing PPD, safe, novel, and efficient preventive interventions are needed. Since large 1‐day workshops appear to successfully treat depression, given the widespread interest and investment of public health units across Canada in maternal and child health, Online 1‐Day CBT‐Based Workshops for Preventing PPD should be developed and tested for their ability to prevent PPD in Canadian women. Based on longstanding clinical work with women at high risk for PPD, the development of a successful 1‐Day CBT‐Based Treatment Workshop for PPD and its delivery in‐person and online, and an extensive review of the PPD prevention literature, the investigators will develop the content for our prevention workshop as well as an accompanying script and intervention manual for participants (Objective 1). They will then advertise and assess the feasibility of recruiting 15 women into a pilot workshop and seek their feedback on its content, delivery and assessment procedures (Objective 2). Using these data, the workshop will be revised, and the investigators will conduct a small pilot randomized controlled trial (n=60) examining the impact of these workshops on rates of PPD when added to care as usual (CAU) more than CAU alone in addition to a 90‐minute information session on PPD (Objective 3). These objectives will enable us to develop and deliver this intervention, assess the feasibility of our recruitment strategy, determine recruitment and retention rates, assess study personnel needs, refine the study protocol and estimate effect sizes for group differences in support of a larger, full‐scale trial aimed as assessing the effectiveness of these workshops at reducing the likelihood of developing PPD in women at risk. The pilot study will be considered successful and proceed to a larger trial in the future if: 1. The treatment manual for the workshop is acceptable to women 2. 15 women are recruited into a pilot workshop within three months and have 70% complete their follow‐up measures 3. Recruit and randomize 60 women over six months into two separate workshop/info sessions (each consisting of 15 in the workshop and 15 into the control information session) and: 1. 70% of eligible sign‐ups enroll in the study 2. 75% of participants assigned to experimental group complete intervention 3. 70% of participants complete all follow‐up measures 4. Estimate a treatment effect and variance (measured using Mini International Neuropsychiatric Interview Major Depressive Disorder Module and the Edinburgh Postnatal Depression Scale)

Nct (2021). "3D vs 2D-laparoscopy for Rectocele and Rectal Prolapse Correction: a Prospective, Randomized, Single Center Study." ClinicalTrails.gov.
	The aim is to compare proximate and remote results of 3D and conventional 2D laparoscopic interventions in terms of efficacy and safety in treatment of symptomatic rectocele and rectal prolapse. This is a prospective randomized comparative study in parallel groups conducted in single Colorectal unit. Inclusion criteria: female patients with stage 3 rectocele (3‐4 POP‐Q [pelvic organ prolapse quantification] grade) and/or full‐thickness rectal prolapse. Intervention ‐ laparoscopic ventral rectopexy. The primary outcome is objective cure rate of pelvic prolapse. Secondary outcomes include obstructive defecation and incontinence symptoms according to Wexner and Cleveland Clinic scales, and satisfaction according to Patient Global Impression of Improvement questionnaire. Operative times, intraoperative blood loss, length of hospital stay, postop pain severity, urinary incontinence, as well as surgical and mesh complications are also assessed. The specific point of interest in this study is surgeon's tiredness after the operation assessed with Profile of Mood States questionnaire.

Nct (2021). "Acupuncture for Overactive Bladder in Adults." ClinicalTrails.gov.
	This randomized, controlled trial is aimed to assess the effectiveness and safety of acupuncture in the treatment of overactive bladder (OAB) in adults. Eligible participants will be randomly allocated to acupuncture or sham acupuncture. To minimize the evaluation bias, the outcome assessors and statisticians will be masked to treatment allocation besides participants.

Nct (2021). "Adductor Strengthening and Pelvic Floor Muscle Strengthening Exercises on Stress Incontinence in Gym Females." ClinicalTrails.gov.
	Stress incontinence is common form of urinary incontinence in females. When it develops in gym doing women, it badly affects their performance and result in psychosocial problems in addition to the barriers that already have been resulted from incontinence. This study combines simple regime of hip adductor a strengthening with pelvic floor muscles. The theme is to test if pelvic floor muscle training can be augmented by incorporating adductor muscle strengthening. If this comes out to be effective, this can be great contribution to gym doing females to improve their urinary incontinence related impairments. Woman would be encouraged to continue regular exercise. This will be randomized clinical trial. There are two groups for the compression of adductors strengthening and pelvic floor muscle strengthening. Group A: with pelvic floor muscle strengthening plus adductor is strengthening. Group B: with pelvic floor muscle strengthening. The collected data will be entered in Statistical Package for the Social Sciences 20.0, Descriptive and Inferential statists will be applied. Results and conclusion will be drawn.

Nct (2021). "Adjuvant Radiotherapy in Patients With Early Endometrial Cancer." ClinicalTrails.gov.
	After being informed the study and potential risk，all patients giving written informed consent will be undergo a 1‐week screening period determine eligibility for study entry. At week 0, patients who meet the eligibility will be randomized in a 1:1 ratio to vaginal brachytherapy or pelvic external beam radiotherapy. After treatment, patients were followed up regularly.

Nct (2021). "Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected." ClinicalTrails.gov.
	This study will include adult women with platinum resistant or refractory high‐grade serous ovarian cancer, with no germline BRCA mutation detected. Participants will be randomized in a 1:1 ratio to either alpelisib plus olaparib or single agent cytotoxic chemotherapy (paclitaxel or PLD) in this open‐label, active controlled study. Participants will continue to receive study treatment until disease progression, unacceptable toxicity that precludes further treatment, or until discontinuation of study treatment due to any other reason. After treatment discontinuation, all participants will enter in the post‐treatment follow‐up period, which consists of a safety follow‐up visit and a 9‐week post‐progression visit. Once they complete the post‐treatment follow‐up, participants will then enter the survival follow‐up period.

Nct (2021). "Alternate Day Versus Daily Oral Iron Therapy in Adolescents." ClinicalTrails.gov.
	The research will be conducted at the following location(s): Baylor College of Medicine, TCH: Texas Children's Hospital, and TCH: Texas Children's Hospital Clinic. If patient appears to qualify for the study they will sign and date this consent form, and the doctor will confirm that they are eligible for the study. The patient will complete the following procedures: ‐ Medical history including prior hospitalizations, lab results, medications, diet, social and family history ‐ Physical Examination ‐ Blood samples: The patient will not have any extra blood draws (pokes) for this study. However, we will ask to take about 1/2 (0.5) teaspoons (3 mL) of extra blood for an extra research test when you have follow up blood test(s) in one month. Patient will be on the study for 24 weeks (6 months),and will receive an information sheet about how to take iron to help it absorb in the stomach and on iron‐rich foods. There are 2 different treatments in this study. If a patient enrolls, they cannot choose which treatment to receive. Instead, they will be randomly assigned to one of the two treatments. That means there is a fifty percent chance they will receive iron medicine to take every day and a fifty percent chance they will receive iron medicine to take every other day.

Nct (2021). "Ancillary Study of the Lessening Incontinence With Low-impact Activity Study." ClinicalTrails.gov.
	The parent trial that supports this ancillary research is a randomized controlled trial to evaluate the efficacy of a group‐based yoga intervention to decrease the frequency and impact of urinary incontinence in ambulatory middle‐aged and older women. Women aged 50 years and older who report daily or more frequent stress‐, urgency‐, or mixed‐type incontinence, are not already engaged in formal yoga or muscle stretching/strengthening programs, are willing to temporarily forgo other clinical treatments for incontinence, are able to walk to and use the bathroom without assistance, and meet other eligibility criteria are being recruited from multiple locations surrounding the San Francisco Bay area. Following a series of telephone‐ and then clinic‐based screening assessments, including a voiding diary to confirm the frequency and clinical type of incontinence, eligible women are randomized in a 1:1 ratio to participate in either a 3‐month yoga program (N 110) or a time‐equivalent, non‐specific muscle stretching and strengthening control program (N 110). During the 3‐month intervention period, participants participate in structured intervention programs (either yoga‐specific or muscle stretching‐strengthening) consisting of twice weekly, 90‐minute group classes led by trained instructors). They are also be instructed to practice their assigned intervention for at least an additional hour per week, with the assistance of participant manuals created by the study team and a set of home yoga or stretching/strengthening exercise props. For this ancillary trial research, the investigators are examining ancillary measures of a) physical performance status, b)perceived stress, depression, and anxiety symptoms, and c) sleep quality, duration, and continuity, already incorporated by the principal investigator into the parent trial. The investigators will examine prospective relationships between these ancillary measures and participant‐reported urinary incontinence frequency/severity/impact, examine intervention effects on these ancillary outcomes, and assess the extent to which these ancillary outcomes mediate intervention effects on incontinence frequency/severity/impact.

Nct (2021). "Antenatal Chlamydia Trachomatis and Neisseria Gonorrhoeae Testing to Prevent Adverse Neonatal Consequences." ClinicalTrails.gov.
	In this study investigators are conducting a two‐arm, cluster randomized trial to assess the effectiveness of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing and treatment during pregnancy to reduce adverse pregnancy and birth outcomes compared to the standard of care (treatment based on symptoms and signs). Investigators will enroll 500 asymptomatic pregnant women in the testing and treatment clinics, and they will receive CT and NG testing and appropriate treatment at their first antenatal care visit and at a visit during their third trimester. An additional 250 asymptomatic pregnant women will be enrolled in the standard of care clinics, and they will receive syndromic management with additional support for partner notification. All participants will be tested for CT and NG at the first postnatal visit and those who test positive will be offered infant testing. Investigators will determine if antenatal testing and treatment reduces maternal infections at delivery, preterm birth, low birth weight, and neonatal CT/NG infection. This study will provide evidence to help evaluate the effects of testing on vertical transmission and clinically important pregnancy neonatal health outcomes, and to evaluate and understand biological correlates of transmission.

Nct (2021). "Antitumor Activity of Neoadjuvant Chemotherapy With or Without BINTRAFUSP ALFA in Patients With Metastatic Advanced Stage Ovarian Cancer." ClinicalTrails.gov.
	BINTRAFUSP ALFA (M7824) is a bifunctional fusion protein that combines an anti‐PD‐L1 antibody and the extracellular domain of TGFβ receptor II (TGFβRII) as a TGFβ neutralizing 'trap', into a single molecule. The novel design of BINTRAFUSP ALFA (M7824), which neutralizes TGFβ and simultaneously inhibits the anti‐PD‐L1 pathway in the tumor microenvironment, may be more effective than agents targeting PD‐L1 and TGFβ separately. In this trial, approximately 33 total patients are expected to be enrolled. The first phase of the study will be the safety lead in in 6 patients with advanced stage (stage III‐IV) ovarian cancer undergoing neoadjuvant settings. Then 27 patients will be enrolled and randomized in 2:1 design to received standard chemotherapy with carboplatin/paclitaxel +/‐ M7824 respectively (N=18:9). Participants will be randomized so that there will be 24 PD‐evaluable participants treated with standard of care chemotherapy plus BINTRAFUSP ALFA and 9 participants treated with standard of care chemotherapy at the end of the study. The control arm is strictly for comparison of the exploratory endpoints, although the primary and secondary endpoints will be presented for both arms, separately. The goal of including 9 patients in the control group is for comparison of the translational endpoint and not the clinical endpoint. For both regimens: M7824 (2400 mg flat dose iv on day 1 every 21 days) with chemotherapy including carboplatin AUC 5 and paclitaxel 175 mg/m2 on day 1 of 21‐day cycle. Interval debulking surgery will be planned after 4 cycles. Chemotherapy will be planned for 6‐8 cycles then maintenance M7824 will be continued for at 12 months.

Nct (2021). "APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion." ClinicalTrails.gov.
	PRIMARY OBJECTIVES: I. Determine the safety of APL‐2 (Pegcetacoplan) alone and in combination with pembrolizumab, and APL‐2 in combination with both bevacizumab and pembrolizumab in patients with recurrent ovarian cancer with symptomatic malignant effusion II. Effect of therapy on of malignant effusion measured by total volume of effusion drained every 3 weeks (patient diary and/or drained volume). SECONDARY OBJECTIVES: I. Determine progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR) and overall survival (OS) II. Changes in quality of life measures during the clinical trial This is a single center, randomized, Phase 2 clinical trial of APL‐2 in combination with Pembrolizumab or in combination with Bevacizumab and Pembrolizumab vs. Bevacizumab alone in patients with recurrent ovarian/fallopian tube/primary peritoneal cancer and persistent malignant effusions. A safety‐lead in cohort of 3‐5 patients, (patients will receive APL‐2 alone for 2 weeks prior to adding pembrolizumab or pembrolizumab and bevacizumab) will be recruited to assess the safety of APL‐2 alone, determine PK/PD levels is serum and malignant effusion and to test the short‐term single‐agent APL‐2 effects on malignant effusion. If no concerning treatment limiting toxicity signal is seen, the randomized expansion cohorts (2B) are allowed to start. Patients will be randomized to 1 of 3 cohorts (2 experimental arms and 1 standard of care control arm). COHORT 2B‐1: APL‐2 (Pegcetacoplan) and pembrolizumab (experimental arm) COHORT 2B‐2: Pegcetacoplan, pembrolizumab and bevacizumab (experimental arm) COHORT 2B‐3: Bevacizumab only (control arm) Treatment repeats every 3 weeks and treatment will continue until disease progression, patient withdrawal or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter up to 3 years.

Nct (2021). "Aspirin for the Management of Endometriosis-associated Pelvic Pain." ClinicalTrails.gov.
	Endometriosis‐associated pelvic pain (EAPP) is common in endometriosis and pain control is an important goal of long‐term management. Non‐steroidal anti‐inflammatory drugs and oral contraception are the two first line therapies for endometriosis.However, there is currently a lack of high‐quality clinical studies of nonsteroidal anti‐inflammatory analgesic in controlling EAPP. The aim of this study is to explore the efficacy and safety of low dose aspirin therapy in management of EAPP. In this study, the investigators hypothesis that aspirin is effective in controlling EAPP. A randomized, open, and controlled study will be implemented. Subjects were recruited in strict accordance the inclusion and exclusion criteria at the outpatient clinic. Patients with EAPP with visual Analogue Scale(VAS:0‐100mm）>30mm will be included. Eligible subjects were randomized according to a computer‐generated randomization schedule to to receive aspirin（75mg/day）or Yasmin(Drospirenone ethinyl estradiol tablet) in a ratio of 1:1. Specific doctors will be designated for the disease diagnosis and ultrasonic examination.The investigators were guided by EAPP pain score and drug use management. The primary efficacy end points is the reduction of the pain score of EAPP at 24th week assessed with VAS score. Pelvic examination, sonography and blood test will be to performed to evaluate the lesion and coagulation function. The specification of the CONSORT case report system will be implemented. Sample size assessment according equivalence study.Follow‐up and loss cases were strictly controlled. A two‐sided test will performed with beta=0.80 and αlpha=0.025. The expected loss rate is calculated at 15%. 220 cases will be enrolled with 110 cases in each group. The study will be accepted regular monitoring and inspection.

Nct (2021). "Azithromycin to Improve Latency in Exam Indicated Cerclage Control Trial." ClinicalTrails.gov.
	Preterm birth (PTB) continues to be a leading cause of neonatal morbidity and mortality. The rate of spontaneous PTB (delivery before 37 weeks gestation) is one in ten pregnancies and a history of prior preterm birth remains a risk factor for recurrence. The pathophysiology of cervical insufficiency leading to PTB remains poorly understood. While interventions for PTB prevention are limited, the American College of Obstetrics and Gynecology (ACOG) supports the use of cervical cerclage. A physical exam indicated cerclage may be placed in the setting of painless cervical dilation in the second trimester. The cerclage is believed to provide mechanical support to a weakened cervix and promote the cervical mucosal plug as a barrier to ascending infection. While many aspects of cerclage use have been extensively studied, the use of antibiotics prior to placement remains under evaluated. While antibiotic use is recommended during cesarean section, preterm premature rupture of membranes (PPROM), and obstetric anal sphincter injuries (OASIS), ACOG currently does not recommend perioperative antibiotics or prophylactic tocolytics at the time of cerclage placement citing insufficient evidence. Miller et al. performed a randomized controlled trial (RCT) showing an increased incidence of pregnancy prolongation by at least 28 days among women who received indomethacin and perioperative antibiotics in the setting of an exam indicated cerclage compared to those who received no perioperative medications (92.3% vs 62.5%, p=0.01). Participants in the experimental arm received cefazolin or clindamycin if they had a penicillin allergy. Cefazolin is a first generation cephalosporin that has activity against gram positive cocci and gram negative rods and is commonly used for surgical prophylaxis. Clindamycin is a protein synthesis inhibitor and covers gram positive organisms and anaerobic bacteria, making it an appropriate alternative in cases of penicillin allergy. The use of cefazolin specifically with indomethacin has been studied retrospectively and showed a significant improvement in gestational latency (adjusted relative risk [aRR] 1.21, 95% CI 1.05‐1.40) and birth weight (+489.8 grams, 95% CI 64.6‐915.0). The use of prolonged azithromycin with cerclage has been studied in a prospective, non‐ randomized fashion. In this study, patients were given 500mg azithromycin for 3 days and this was repeated every 10 days until 34 weeks. Patients who received this regimen and a cerclage had lower PTB (65.7% vs 5.7%, p<0.001) and reduced immediate fetal mortality (37.1% vs 0%, p<0.001). The aim of our study is to determine if the addition of azithromycin prior to exam indicated cerclage prolongs gestation. Azithromycin is a macrolide antibiotic that binds to the 50S subunit of the bacterial ribosome and inhibits transpeptidation. It is effective against a wide variety of bacteria, specifically mycoplasma which has been associated with preterm birth. Azithromycin is currently used in obstetrics for patients undergoing nonelective cesarean delivery and as part of latency antibiotics in the setting of PPROM.

Nct (2021). "Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer (BRAVA)." ClinicalTrails.gov.
	The purpose of this Phase 3 trial is to demonstrate prolongation of OS in patients treated with BAL as compared to IC chemotherapy. This Phase 3 trial is an open‐label, randomized study with single‐agent BAL or IC chemotherapy (single‐agent gemcitabine, irinotecan, pemetrexed, vinorelbine, or topotecan) in patients with recurrent, persistent, or metastatic cervical cancer who have progressed after receiving platinum based chemotherapy. Population: Patients with recurrent, unresectable, or metastatic cervical cancer who have progressed after receiving at least 1 prior line of platinum‐containing chemotherapy with or without bevacizumab. In this study, > 50% of patients will have received prior treatment with bevacizumab, which will be determined prior to enrollment. Stratification ‐ Histology (squamous cell carcinoma [SCC] vs adenocarcinoma [AC] or adenosquamous carcinoma [ASC]) ‐ Region of the world (United States or Europe Union or Australia vs other countries) ‐ Eastern Cooperative Oncology Group (ECOG) status 0 vs 1 Randomization • 2:1, BAL: IC chemotherapy Approximately 486 patients will be enrolled and randomized with 2:1 allocation between the BAL and IC chemotherapy arms.

Nct (2021). "Bioenergetics of Exercise-Induced Menstrual Disturbances." ClinicalTrails.gov.
	Long term energy deficiency in women can lead to functional hypothalamic amenorrhea (FHA), which can cause many health detriments such as osteopenia, stress fractures, transient infertility, dyslipidemia, and impaired endothelial function. Though studies involving diet and exercise interventions have shown how energy deficiency can lead to menstrual disturbances prospectively, this study aims to extend those findings by measuring the magnitude of energy deficit that could lead to these disturbances. Hypotheses for this study are: 1) there would be a dose‐response relation between the induction of menstrual disturbances (luteal phase defects, anovulation, and oligomenorrhea) and the magnitude of energy deficiency such that the intervention groups experiencing a greater energy deficit would incur a significantly greater incidence of menstrual cycle disturbances and 2) the intervention groups experiencing a greater energy deficit would incur a greater incidence of more severe menstrual cycle disturbances. The study included one baseline menstrual cycle and 3 intervention menstrual cycles. During the baseline period, participants were randomly assigned to an experimental group for intervention menstrual cycles 1, 2, and 3 of the study. The goal of the subject groupings was to test the impact of varying levels of an energy deficit created by the combination of caloric restriction and exercise on menstrual function. They were assigned to either a control group that did not exercise and consumed a number of calories estimated to maintain body weight, a control group that exercised but received extra food calories to remain in energy balance (EXCON), or one of four groups that exercised and were prescribed reduced energy intake to create varying levels of an energy deficit. Specifically, the four groups of energy deficit were 1) an increase of 15 percent kcal of exercise (15 percent deficit, ED1), 2) an increase of 30 percent kcal of exercise (30 percent deficit, ED2), 3) a decrease of 15 percent in dietary intake combined with an increase of 15 percent of exercise, (30 percent deficit 15/15, ED2), and 4) a decrease of 30 percent in dietary intake combined with an increase of 30 percent kcal of exercise (60 percent deficit, ED3). The number of participants for analysis was 34 participants in the following groups: EXCON (n = 8), ED1 (n = 6), ED2 (n = 12), and ED3 (n = 8). Baseline energy needs were assessed during the baseline cycle. Resting metabolic rate and nonexercise physical activity were added to determine a caloric need for the day. Caloric intake was supervised throughout the entire study, and meals were comprised of 55 percent carbohydrates, 30 percent fat, and 15 percent protein. Exercise training was also supervised, and maximal oxygen consumption (VO2 max) was calculated. Menstrual status was assessed through analysis of daily urinary metabolites of estrone‐1‐glucuronide (E1G), pregnanediol glucuronide (PdG), and midcycle LH. Underwater weighing and a digital scale were used to assess body composition, and fasting blood samples were collected to assess metabolic hormones.

Nct (2021). "Calcium Chloride for Prevention of Blood Loss During Intrapartum Cesarean Delivery." ClinicalTrails.gov.
	Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Up to 80% of PPH is caused by uterine atony, the failure of the uterine smooth muscle to contract and compress the uterine vasculature after delivery. Laboratory and epidemiological studies show that low extracellular and serum calcium levels, respectively, decrease uterine contractility. A pilot study performed by the investigators supports the hypothesis that intravenous calcium chloride is well tolerated and may have utility in preventing uterine atony. The proposed research will establish the relationship between uterine tone and calcium through a clinical trial with an incorporated pharmacokinetic and pharmacodynamic (PK/PD) study. In a randomized, placebo‐controlled, double‐blind trial, investigators will establish the effect of 1 gram of intravenous calcium chloride upon quantitative blood loss and uterine tone during cesarean delivery in parturients with high risk of uterine atony. Investigators will concurrently collect serial venous blood samples to measure calcium for PK/PD modeling in this pregnant study cohort. High‐quality clinical research and development of novel therapeutics to manage uterine atony are critical to reduce the high maternal morbidity and mortality from PPH.

Nct (2021). "Camrelizumab Combined With Famitinib Malate for Treatment of Recurrent/Metastatic Cervical Cancer." ClinicalTrails.gov.
	This study is a randomized, open‐label, controlled, multi‐center Phase III clinical study, aimed to evaluate the efficacy and safety of camrelizumab combined with famitinib malate versus platinum‐based chemotherapy in the treatment of recurrent/metastatic cervical cancer. All enrolled patients will be randomly divided into 2 groups and continuously treated until any event that meets the criteria for end of the clinical trial.

Nct (2021). "Carbon Dioxide Acupulse Laser Treatment Versus Sham Treatment and Stress Urinary Incontinence Symptoms." ClinicalTrails.gov.
	Following a screening visit, eligible subjects will be enrolled into the study. Subjects will be randomized into either laser treatment or sham treatment. Each subject will receive 3 treatments 4 weeks apart and 3 follow up visits, at 3, 6 and 12 months following the last treatment. Further demographic information and patient history will be obtained from the subjects' electronic files.

Nct (2021). "Chiauranib Plus Weekly Paclitaxel in Patients With Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer." ClinicalTrails.gov.
	Chiauranib is a novel orally active multi‐target inhibitor that simultaneously inhibits the angiogenesis‐related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRa and c‐Kit), mitosis‐related kinase Aurora B and chronic inflammationrelated kinase CSF‐1R in a high potency manner with the IC50 at a single‐digit nanomolar range. In particular, Chiauranib showed very high selectivity in the kinase inhibition profile with little activity on off‐target non‐receptor kinases, proteins, GPCR and ion channels, indicative of a better drug safety profile in terms of clinical relevance. Patients will be randomized to receive treatment with either paclitaxel + Chiauranib or paclitaxel + placebo. Paclitaxel will be repeated every 21 days for a maximum of 6 cycles. Patients with objective response/stable disease after completing 6 courses of chemotherapy will continue Chiauranib or placebo until progression.

Nct (2021). "Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders Study." ClinicalTrails.gov.
	This project is the fourth in a series of randomized, double‐blind controlled trials of choline bitartrate in children ages 2‐5 (under 6) years with prenatal alcohol exposure. Pre‐clinical data suggests that choline may attenuate the cognitive deficits caused by prenatal alcohol exposure (especially memory deficits). This study will evaluate the effects of daily choline supplementation in two dosing regimens (3 months choline vs. 6 months choline). Outcome measures include an elicited imitation memory paradigm, IQ measures, and measures of memory and executive functioning, and behavior.

Nct (2021). "Clinical Efficacy of Adjuvant Chemotherapy in Patients With Locally Advanced Cervical Cancer Who Did Not Meet the NCCN Guidelines for Adjuvant Treatment After NACT Combined With Surgery." ClinicalTrails.gov.
	This is a prospective, phase 3 randomized controlled clinical trial. Cervical cancer patients with FIGO stage IB3, Ⅱ A2 or IIB with tumor size> 4 cm will be enrolled. Patients will undergo 2‐3 cycles of neoadjuvant chemotherapyradical (NACT) followed by laparotomic or laparoscopic hysterectomy + pelvic lymphadenectomy with cervical cancer foci sealed before dissection of the vagina and without uterine manipulator. Patients meet criteria of adjuvant therapy according to NCCN guideline after surgery will be weeded out, and who do not meet criteria of adjuvant therapy will be randomly selected to undergo adjuvant chemotherapy or just follow‐up visit. The primary endpoint was disease‐free survival (DFS) rate at 5 year. The secondary endpoints were 5‐year overall survival (OS), safety and quality of life.

Nct (2021). "Clinical Response and Toxicity of Hypo-fractionated Chemoradiotherapy in Cervix Cancer." ClinicalTrails.gov.
	In this study we aim to determine if clinical response and toxicity of radiotherapy hypofractionation is non‐inferior to the conventional treatment. We will enroll 60 eligible patients with cervical cancer stage IB to IIIC and randomly allocate them into the intervention (hypofractionation) group or the control (standard) groups. The patients in the intervention group will receive external beam radiotherapy(EBRT) to a total dose of 40 Gy in 15 fractions within 3 weeks concurrently with weekly chemotherapy with cisplatin 40mg/m2 (total of 3 cycles). Whereas, the control group will receive EBRT to a total dose of 45 Gy in 25 fractions within 5 weeks concurrently with weekly chemotherapy with cisplatin 40mg/m2 (total of 5 cycles). All patients from both groups will undergo high dose rate brachytherapy one week after completion of EBRT to a total dose of 28 Gy per 4 weekly sessions. Patients will be evaluated regarding early and late toxicities as described by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at the completion of brachytherapy, and at 3 months, 6 months, and 3 years from completion of treatment. Also, clinical response will be evaluated through dynamic contrast enhanced pelvic MRI 3 months, 1 year, and 3 years after completion of brachytherapy.

Nct (2021). "A Clinical Study of Intravaginal Prasterone (Intrarosa®) in Postmenopausal Vulvovaginal Atrophy." ClinicalTrails.gov.
	The phase 1 study which includes the screening phase (up to 3 weeks) and treatment phase (12 weeks). After signing the informed consent, the inclusion and exclusion criteria will be confirmed preliminarily at screening visit and reconfirmed at Day 1 (baseline). At least 418 eligible subjects will be randomized in a 1:1 ratio to receive 6.5mg of intravaginal prasterone or placebo once‐daily for 12 weeks. The phase 2 study which includes the treatment phase (26 weeks). A total of 100 subjects who have completed Phase 1, not occur adverse event（AE） grade ≥3 or serious adverse event (SAE), or recover all AE grades ≤1, and voluntary to participate in Phase 2 study. After signing the ICF, the subject will receive 6.5mg of intravaginal for 26 weeks.

Nct (2021). "A Clinical Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsules Versus Paclitaxel as Weekly Treatment of Relapsed Platinum-resistant Ovarian Cancer." ClinicalTrails.gov.
	A clinical study to evaluate the efficacy and safety of TQB2450 injection combined with Anlotinib Hydrochloride capsules versus weekly treatment with paclitaxel of recurrent platinum‐resistant ovarian cancer.A total of 405 subjects will be enrolled.

Nct (2021). "A Clinical Study on Adherence and Efficacy of Different Doses of Active Iron in Treatment Resistant Subjects." ClinicalTrails.gov.
	More than 2.2. billion people worldwide have anaemia and half of this burden is caused by iron deficiency [Lopez 2016]. The commonest causes of iron deficiency are inadequate intake, poor absorption of iron [Stoffel 2017] and blood loss, for example due to menstruation [World Health Organization Guideline: Daily iron supplementation in adult women and adolescent girls; Geneva 2016, Low 2016]. Supplementation with oral iron is well established to prevent and treat iron deficiency anaemia and to promote recovery of iron and haemoglobin levels post blood loss or blood donation [Low 2016, McNamee 2013]. However, iron food fortification and oral iron supplements are frequently limited by poor absorption and poor tolerability [Munoz 2009]. Ferrous sulfate is considered the gold standard and the only oral iron form on the WHO Essential Medicines List, yet has fractional absorption of only 16%‐21% from daily or alternative daily doses [Stoffel et al 2017]. It is also poorly tolerated, causing adverse GI effects in a majority of patients [Pereira 2014]. This results in poor adherence in up to 50% of users, significant nutritional deficit and treatment failure [Tolkien 2015] We have previously evaluated a formulation of microspheres of iron sulfate in a denatured whey protein (WP) matrix at a daily elemental iron dose of 25mg daily, marketed as Active Iron, in comparison with equi‐dose immediate release and modified release ferrous sulfate (Wang et al. Acta Haematologica Acta Haematol 2017;138:223‐232). In these evaluations, the iron‐WP formulation has shown better absorption and there were no reports of adverse effects. Furthermore, in‐vitro data show that the iron‐WP matrix formulation can protect HT20 gut endothelial cells and CaCO2 cells from oxidative stress and cell damage associated with ferrous sulfate. In a post‐marketing survey of 101 people taking Active Iron (age 43 ± 10 years, 83% female) with a history of intolerance to oral iron, 87% reported no adverse effects after 2 weeks. Therefore, the present study aims to compare the 3‐month adherence and efficacy associated with a 25mg single daily dose, a lower (14mg) single daily dose and twice daily dosing with 25mg (50mg daily), in subjects with treatment failure (iron deficiency and with a history of intolerance to oral iron). The primary objective of the study is to assess the proportion of subjects adherent and persistent (>80% based on pill counts) from baseline to weeks 6 and baseline to week 12. Secondary objectives aim to further assess compliance (average compliance), tolerability (incidence of gastrointestinal symptoms GSRS instrument), efficacy (change in haemoglobin, ferritin, transferrin saturation, iron binding protein) and health related quality of life (SF36 instrument). At least 90 subjects will be screened in order to identify up to 60 eligible subjects, and 54 evaluable subjects. Participants will be male and female, between 18 and 55 years of age, with mild to moderate iron deficiency anaemia (haemoglobin ≥9.5 g/dL and <12.0 g/dL for females and ≥10.0 g/dL and <13.0 g/dL for males and ferritin < 30 µg/L) or ferritin < 30 µg/L and no anaemia. There will be stratified randomisation to include up to 30 patients with iron deficiency and mild to moderate anaemia as well as up to 30 patients with iron deficiency without anaemia. Other pre‐specified sub‐groups for evaluation of the primary and secondary endpoints include women with reported symptoms of heavy menstrual bleeding and participants with intolerance of liquid iron products or lower doses (< 50mg elemental iron). Separate analysis of primary and secondary endpoints will be carried out in participants in the multivitamin and mineral sub study. Finally, due to the suspension of some clinics during Covid lockdown, we carried out a prespecified analysis of patients completing the study before the onset of the Covid 19 Pandemic. Subjects will be randomised to one of three treatment arms: 1. ACTIVE IRON™ (ferrous sulfate) 14 mg elemental iron once daily (plus matching p cebo) 2. ACTIVE IRON™ (ferrous sulfate) 25 mg elemental iron once daily (plus matching placebo) 3. ACTIVE IRON™ (ferrous sulfate) 25 mg elemental iron twice daily (plus matching placebo) The study will involve 4 visits over a 12 to 14‐week period. At the screening visit (visit 1), informed consent shall be obtained. Demographic data, vitals, anthropometric measurements and prior and concomitant medications will be recorded. Subjects will be asked questions relating to their iron deficiency anaemia and medical history associated with this. Female subjects will be asked questions regarding their menstrual periods and intolerance to other iron products. A fasting blood sample will be collected and a full blood count, including Ferritin and Serum iron/Transferrin will be measured. Blood and serum samples will be frozen and retained for post‐hoc analysis of other biomarkers relevant to iron metabolism (e.g. hepcidin, soluble transferrin receptor). Once eligibility is confirmed the subject will be invited to attend a baseline visit (visit 2, Time 0). At this visit, a blood sample will be collected and a full blood count, including Ferritin and Serum iron/Transferrin will be measured. For women of childbearing age, a urine sample will be collected, and pregnancy test performed. Subjects will be queried about any changes in their health status and any non‐treatment emergent events and medications will be recorded. Subjects will complete the following questionnaires: Gastrointestinal Symptom Rating Scale (GSRS Instrument), the Short Form‐36 (SF‐36 Instrument) and for women who are menstruating, they will report the date, duration and blood flow of their last menstrual period. Subjects will be randomized into one of three treatment groups, but will be blinded as to which group they are in. Subjects will be supplied with a 6‐week supply of study product and instructions on dosing. Subjects will be instructed to following their habitual diet and exercise routine and to not consume any disallowed medications or supplements that could interfere with the assessment of the study product for the duration of the study. Subjects will be provided with an appointment to return to the study site at week 6. At week 3 and 9 ('phone visits'), all subjects will be asked (to complete the GSRS, and women who are menstruating, will complete Menstrual Period Questionnaire, to record the date, duration and blood flow of their last menstrual period. Subjects will return to the clinic site at week 6 (visit 3) and 12 (visit 4). At each visit, subjects will be queried about any changes in their health status and any adverse events and medications will be recorded. A blood sample will be collected and a full blood count, including Ferritin and Serum iron/Transferrin will be measured. Subjects will complete the following questionnaires: GSRS, SF‐36 and for women who are menstruating, the Menstrual Period Questionnaire. Subjects will return any unused study product and additional product will be dispensed. The adherence based on pill count will be determined for the period. Subjects will be instructed to continue following their habitual diet and exercise routine and to not consume any disallowed medications or supplements that could interfere with the assessment of the study product for the duration of the study. At the 4th visit (week 12), subjects will be invited to partake in an optional, open‐label, follow‐up for 3 months after the completion of the blinded intervention phase. Participants who decide to partake in the optional, open‐label follow‐up study will continue to receive the same dose of Active Iron™ as they received during the blinded intervention phase, for a further 12 weeks, in addition to a multivitamin and mineral complex that is designed to maximise iron metabolism and haemoglobin/red blood cell formation. This complex contains vitamin A, D, B2, B6, B12, folic acid and copper. Subjects will return for an interim follow‐up visit at week 18 (visit 5), and a final visit at week 24 (visit 6). At these visits sub cts will undergo standard assessments and complete the following questionnaires: GSRS, SF‐36 and for women who are menstruating, the Menstrual Period Questionnaire. Subjects will also answer questions on the tolerability of the study product.

Nct (2021). "Clinical Study to Evaluate the Efficacy of Prasterone Treatment for Atrophy Vulvovaginal in Postmenopausal Women With Vulvar / Vestibular Pain." ClinicalTrails.gov.
	A sample of 50 women over 45 years of age with at least one year of amenorrhea and who require treatment for vulvovaginal atrophy of moderate and / or severe intensity and who present vulvar and vaginal pain within these symptoms will be chosen. At the beginning of the study, after passing the selection criteria and signing the informed consent, the patients will be randomly assigned to one of the two arms of the study, (active group) or (control group), said assignment will be made randomly. Through a computer program where one or the other arm of treatment will be assigned to the patient at random to guarantee the homogeneity of both study groups and thus avoid selection biases.

Nct (2021). "Comparative Study Between Combined Vaginal Misoprostol." ClinicalTrails.gov.
	"Comparative study between Combined Vaginal Misoprostol with Isosorbide‐5‐Mononitrate versus Misoprostol Alone For Induction Of The first trimester Missed Abortion A Randomized Clinical Trial"

Nct (2021). "Comparative Study Between Fresh and Frozen Embryo Transfer in PCOS Patients Undergoing IVF Treatment." ClinicalTrails.gov.
	Eligible women will be randomized to two groups in a ratio of 1:1 . Both the patients and the clinicians will be aware of the allocated arm. The patients (110) will be equally randomized into two groups: Group A will undergo a day 3 fresh embryo transfer after ovarian stimulation, luteal phase support will be started just after follicular aspiration. Group B will have all of their embryo cryopreserved after ovarian stimulation with no luteal phase support after the aspiration and then undergo a frozen‐thawed day 3 embryo transfer. Controlled ovarian stimulation will be done using the gonadotropin releasing hormone (GnRH) antagonist protocol then human chorionic gonadotropin( HCG) 5000 IU trigger for final oocyte maturation.

Nct (2021). "Comparing Effects of Kinesio and Dynamic Tapings in Postpartum Women With Pelvic Girdle Pain." ClinicalTrails.gov.
	The main purpose for this study are to investigate the effects of KT and DT on pain, disability, physical functions, and quality of life, as well as PFM functions in postpartum women with PGP. 60 postpartum women with PGP will be randomized into one of the three groups:(1) kinesio taping group,(2) dynamic taping group (3)control group, and receive 4 weeks intervention. All participants will receive 3 assessments at the baseline, immediately after first taping session, and after 4‐week interventions. The outcome measures will include Visual Analog Scale measures of pain intensity, Pelvic Girdle Questionnaire/ Oswestry Disability Index/ Patient specific functional scale measures and Global rating of change score. for disability. The quality of life will be measured by 36‐item Short‐Form Survey， The Physical functions include Active Straight Leg Raise Fatigue task , Time up and go test,10‐meter walk test. The PFM functions will be measured by Modified Oxford grading scale and Perineometer. It is expected that PGP women in both the KT group and DT group will have more improvements than the control group. But the DT group will have even more improvements than the KT groups.

Nct (2021). "Comparing Intrathecal Morphine and Intraoperative Lidocaine Infusion to Epidural Anesthesia With Postoperative PCA for Patients Undergoing Exploratory Laparotomy." ClinicalTrails.gov.
	To determine if opioid consumption postoperatively among patients undergoing non‐emergent laparotomy by the gynecologic oncology service who receive intrathecal morphine with intraoperative lidocaine (IML) infusion are lower than patients who have epidural anesthesia with PCA (EPCA).

Nct (2021). "Comparing Number of Injection Sites of In-office Intravesical Onabotulinumtoxin A Treatments for Overactive Bladder: a Randomized Controlled Trial." ClinicalTrails.gov.
	Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urinary incontinence, nocturia, and urinary frequency. Intravesical injection of onabotulinumtoxinA is approved by the US Food and Drug Administration for treatment of neurogenic and idiopathic OAB. Current standard of practice involves 100 U of onabotulinumtoxinA diluted in 10 ml saline cystoscopically injected into approximately 20 different detrusor muscle sites equally distributed along the posterior bladder wall and dome. This treatment was classically done in the operating room under general anesthesia, but now is typically performed in an office setting using local anesthesia (lidocaine) as this is more feasible and tolerable. Patients can experience discomfort and pain with each injection. Evidence has also shown that administering the same dose of onabotulinumtoxinA into fewer injection sites in the detrusor muscle (ranging from 3 to 10) results in equivalent efficacy compared to the current standard. However, it has yet to be determined if there is a significant difference in patient satisfaction and tolerability when the procedure is administered in an office setting using the same dosage with fewer injections. Our study aims to assess whether patient tolerance and satisfaction of intravesicular onabotulinumtoxinA increases with the use of 4 detrusor injections as opposed to 20 injections when performed in an office setting on women with OAB.

Nct (2021). "Comparing Postoperative Pain After Vessel Sealing Device Versus Conventional Suturing Methods for Vaginal Hysterectomy and Pelvic Reconstructive Surgery." ClinicalTrails.gov.
	This study will investigate pain outcomes for patients undergoing vaginal hysterectomy with pelvic reconstructive surgery using the LigasureTM vessel sealing device as compared to conventional clamping and suturing methods.

Nct (2021). "Comparison Between a Telerehabilitation Program for Urinary Incontinence Versus a Conventional Face-to-face Program." ClinicalTrails.gov.
	Randomized longitudinal study including consecutively admitted patients on pelvic floor rehabilitation consultation of the Physical Medicine and Rehabilitation Department of Centro Hospitalar São João for conservative treatment of UI. Patients who meet the inclusion criteria and do not meet any of the exclusion criteria will be randomized one to one between the intervention group and the control group. The intervention group includes a hybrid program of face‐to‐face sessions followed by sessions of video, while the control group develops the entire program in face‐to‐face sessions. The effectiveness of the program will be assessed by the results in the UI‐related quality of life (primary outcome); UI severity, patient's overall perception of improvement, sexual function, depression/anxiety symptoms and satisfaction and adherence to treatment (secondary outcomes).

Nct (2021). "Comparison Between Home-based Wearable Device and Supervised PFMT on SUI/MUI." ClinicalTrails.gov.
	Objective The study is designed to compare the benefit of self‐assessment of a home‐based wearable device assisted pelvic floor muscle training (PFMT) to standard supervised PMFT program for women with SUI/MUI (stress urinary incontinence/mixed urinary incontinence). Background National and international clinical practice guidelines recommend supervised pelvic floor muscle training of at least 3 months' duration as a first‐line treatment to women (including the elderly and post‐natal) with stress or mixed urinary incontinence (Level of evidence A). However, it remains unknown that which component could bring extra benefit when assisted with surprised PFMT. Patients selection and study design The study protocol was approved by the Peking union medical college hospital ethics committee (JS‐3192D, 26/10/2021). Women who had their 6‐week to 3‐month postpartum clinical visits in the member hospitals between Dec 01, 2021 and May 01, 2022 were invited to participate in the study. The women who reported SUI/MUI symptoms within 3 months postpartum were recruited. The exclusion criteria were 1）urgency urinary incontinence alone; 2）a prolapse greater than stage II on examination (>1cm below the hymen on straining); 3）third and fourth degree perineal tear; 4）suffering diastasis recti abdominis and chronic pelvic pain as the primary problem need treatment; 5）a history of stress urinary incontinence(SUI) before pregnancy; 6）had previous pelvic surgery; 7）malignant pelvic cancer; 8）Genurological infection; 9）had received formal instruction on PFMT in the past 5 years; 10）unsuitable to participate because of significant diseases; 11）others:were unable to contract pelvic floor muscles on digital examination when requested;Inability to use the device in vagina. Once each participate was recruited, they were arranged randomly to either an intervention group or a control group (1:1). The intervention group used a wireless wearable vaginal device to record the pressure and practice time and the grade of type I and II pelvic floor muscle fiber strength were assessed by the device once three weeks. The control group accepted the supervised PFMT. Both groups followed the same program three months. During three months, the investigators phoned both groups once three weeks to guide their training. Both groups were assessed by questionnaire and PFM measurements at baseline(pre‐test), 3‐month, 6‐month and 12‐month. The primary outcome is ICIQ‐UI SF; The secondary outcomes include POP‐SS; POP‐Q; Oxford Classification; Pelvic floor muscle surface electromyography; I‐QOL; PISQ‐12; BPMSES. The hypothesis is that the wearable device with self‐assessment function providing PFMT is superior to the supervised PFMT program alone for the treatment of both SUI and MUI of postpartum women.

Nct (2021). "Comparison Between The Effects Of Different Frequencies Of Ultrasonic Cavitation On Abdominal Adiposity And Female Hormones In Polycystic Ovarian Syndrome." ClinicalTrails.gov.
	Participants in both groups were told to follow a low calorie diet (1200 Kcal/day) tailored to their specific needs (low in fat (15%), high in complex carbs (55%), and adequate in protein) (30 percent ) (11). The application procedure of ultrasound cavitation for both groups (A and B):‐ ‐ Each participant in both groups (A and B) received instructions on the treatment techniques as well as the benefits of the USFC. ‐ To improve lymphatic drainage, each subject was encouraged to consume one liter of water before and after the therapy sessions. ‐ Each participant was urged to empty her bladder before beginning each treatment session so order to remain comfortable and relaxed throughout the session. ‐ From a standing position, each participant's abdomen was divided transversally into three sections; see fig (1) 1‐ Part I: from the xiphoid process to 3cm above the umbilicus, 2‐ Section II: from 2cm below the umbilicus to the pubic bone, and vertically to the linea alba, each part was separated into right and left segments, resulting in a total of 6 abdominal segments. ‐ Part III: 3cm above the umbilicus to 2cm below the umbilicus ‐ After washing the skin on the anterior abdominal wall with alcohol, a conducting medium (gel) was placed to the ultrasonic instrument's cavitational head. ‐ The gadget was turned on, a 30‐minute timer was set, and the intensity was gradually increased. ‐ The cavitation head then moved extremely gently in a small circular motion on each abdomen section for 5 minutes. ‐ After completing the ultrasonic application to the six regions of the abdomen, the skin was cleansed with a piece of cotton. For group (A): 40000 HZ ultrasound was delivered for 30 minutes, 3 times/week for 2 months. For group (B):26000 HZ ultrasound was delivered for 30 minutes, 3 times/week for 2 months

Nct (2021). "A Comparison of a PULSE Diet and the TLC Diet on Reproductive, Metabolic Parameters in Women With PCOS." ClinicalTrails.gov.
	The main objective of the study is to identify the effect of pulses on a range of PCOS and metabolic syndrome features. In this parallel clinical trial, 110 (18‐35 years old) women with PCOS will be recruited. Participants will be randomly assigned to either a pulse‐based diet or a therapeutic lifestyle changes‐based diet. The effect of a pulse‐based diet on a range of reproductive and metabolic parameters will be evaluated. The results of this study are anticipated to evaluate the therapeutic merits of a pulse‐based diet for women with PCOS which would influence dietary guidelines.

Nct (2021). "Comparison of Nodal Staging in Endometrial Cancer." ClinicalTrails.gov.
	This study aims to estimate the recurrence‐free survival rates in women with endometrial cancer treated with selective versus sentinel node surgical staging.

Nct (2021). "Comparison of Pain After Uterine Artery Embolization Using Gelatin Microsphere or Tris-acryl Gelatin Microsphere." ClinicalTrails.gov.
	This investigational study is designed to compare pain after uterine artery embolization using Gelatin microsphere or tris‐acryl gelatin microsphere in patients with symptomatic fibroids. The primary end‐points will be evaluated by assessing the maximum Visual Analogue Scale (VAS) score obtained for each time points within 24 hours after embolization. Secondary end‐points consist of evaluating six items: 1) fentanyl and analgesic usage within 24 hours, 2) comparison of symptom severity score and health‐related quality of life score, 3) comparison of postoperative inflammation, 4) assessment of tumor necrosis degree in Magnetic Resonance Imaging, 5) fluoroscopy and procedure time comparison, and 6) assessment of residual ovarian function before and after surgery (Serum AMH). This study included patients between the ages of 20 and less than 60 years of age who were diagnosed with uterine myoma and planned to undergo uterine artery embolization.

Nct (2021). "Comparison of the Effects of Different Massage Techniques in Women With Primary Dysmenorrhea." ClinicalTrails.gov.
	Primary dysmenorrhea is defined as painful menstrual cramps without an underlying pelvic pathology or organic problem. Massage, which is one of the physiotherapy methods that reduces pain by acting on the autonomic nervous system and circulation, has an important place in the management of PD among non‐pharmacological treatment approaches. In the literature, there are studies on the use of classical massage and connective tissue massage in women with PD for reducing menstrual pain and PD‐related symptoms. However, to the best of our knowledge, no study has been found comparing classical massage and connective tissue massage in PD management.

Nct (2021). "Comparison of Treatment of Cervical Intraepithelial Lesions With Imiquimod or LLETZ." ClinicalTrails.gov.
	Imiquimod is one of the target topical drugs for treating HSIL. It is a Toll‐like receptor 7 agonist that acts locally so that it induces cellular response, which can aid in the regression of HPV‐associated lesions. Imiquimod is currently used for treating genital warts. In vitro studies have shown promising effects in the treatment of several diseases, such as endometrial, cervical and prostate cancer, endometriosis, melanoma, and cervical and vulvar intraepithelial lesions. Clinical studies are however lacking. With this in mind, the aim of our study was to evaluate whether topical treatment of HSIL with imiquimod is comparable to standard treatment with LLETZ. As mentioned in the Brief summary, we have set different outcome measures in the experimental and control arm. The different outcome measures were based on moderate accuracy of PAP smear, therefore in order to minimize potential progression of cervical disease to cancer and to avoid LLETZ and possible overtreatment and to assess as accurately as possible the potential residual disease, colposcopy with biopsies will be performed 4 weeks after treatment with imiquimod is completed (20th week after treatment initiation). Follow up after LLETZ will performed using cytology (PAP smear), which is in concordance with our national guidelines. Biopsies will be performed in case of clinically visible lesions. Secondary outcomes of the study are the incidence and severity of the side effects in both groups, which will be evaluated during and after treatment using the 5th version of the Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Other secondary outcomes, namely the need for treatment with LLETZ two years after primary treatment with imiquimod in the experimental arm or re‐treatment with LLETZ two years after primary treatment with LLETZ in the control arm, respectively, and the modulatory effect of imiquimod on immunoregulatory molecules are expected to be available in three years' time after treatment is completed in all patients in both arms.

Nct (2021). "Comparison of Two Different Drug Regimens for Medical Treatment of Early Pregnancy Loss." ClinicalTrails.gov.
	Aim: To investigate the safety and efficacy of combination of mifepristone and misoprostol versus misoprostol alone in medical management of early pregnancy loss. Primary objective: To test the hypothesis that the sequential combination of mifepristone and misoprostol is superior to misoprostol alone for the complete evacuation of uterus in patients diagnosed with early pregnancy loss. Secondary objectives: To test the hypothesis that the addition of mifepristone reduces the need for further doses of misoprostol, duration of bleeding, complication rate and side effect frequency. The investigators will also evaluate if the addition of mifepristone improves patient satisfaction and quality of life. Women with a diagnosis of early pregnancy loss that opt for medical treatment and sign an informed consent will be included. The participants will be randomized to two groups. First group will receive oral mifepristone (600 mg) and the second group will not. The remaining course of treatment will be the same for both groups including giving misoprostol (800 mcg vaginally) 48 hours after receiving mifepristone for the first group or immediately for the second group. 24 hours after receiving first dose of misoprostol, one more dose of misoprostol (also 800 mcg vaginally) will be given if no pregnancy tissue is lost. Three weeks after medical treatment, primary and secondary outcomes will be assessed. In case of unsuccessful treatment (incomplete evacuation of uterus), surgical evacuation will be performed. 220 women will be randomized in a 1:1 ratio.

Nct (2021). "Continuous Erector Spinae Plane Blocks to Treat Postoperative Pain After Open Gynecologic Procedures Via a Low Transverse (Pfannenstiel) Incision." ClinicalTrails.gov.
	Open gynecologic surgery can be significantly painful. With the goal of minimizing the use of opioids (with undesired side effects and potential for abuse), the investigators frequently administer bilateral single‐injection erector spinae plane (ESP) blocks which help to numb the surgical area and decrease postoperative pain. However, the numbing medication typically lasts for only 8‐18 hours. For other peripheral nerve blocks, this duration can be increased with the insertion of a percutaneous catheter‐a tiny tube smaller than a piece of spaghetti‐followed by an infusion of additional local anesthetic. However, the effects of the various peripheral nerve blocks are determined by the anatomy and physiology of the specific peripheral nerve, with an infusion resulting in dramatic benefits for one nerve yet having no effect for another. The potential benefits and risks of adding a catheter and subsequent local anesthetic infusion to a single‐injection ESP block remain unknown. The investigators therefore propose a randomized, triple‐masked, placebo‐controlled, split‐body clinical trial to determine the potential benefits and risks of adding the infusion to single‐injection ESP blocks. Patients undergoing gynecologic surgery via a low transverse (Pfannenstiel) incision who already have bilateral ESP blocks as part of their analgesic plan will be offered enrollment. Participants will have bilateral catheters inserted through the same block needles used for their single‐injections, followed by perineural administration of bupivacaine on one side and normal saline on the other (determined randomly and in a triple‐masked fashion). This will be a single‐center, randomized, triple‐masked, placebo‐controlled, split‐body human subjects clinical trial. Enrollment. Participants will be consenting adults undergoing open gynecologic surgery via a low transverse incision. Study inclusion will be proposed to eligible patients prior to surgery. If a patient desires study participation, written, informed consent will be obtained using a current Institutional Review Board‐approved informed consent form. The study population of interest includes women of all races and socioeconomic status. Inclusion and exclusion criteria are listed in section #10 below. Of note, the investigators will be using local anesthetic, perineural catheters, and infusion pumps as approved/cleared by the Food and Drug Administration and do not plan to research a possible change of indication or use of these medications/devices as part of this research project. Preoperative Procedures. Following written, informed consent, the investigators will record baseline anthropometric information (age, sex, height, and weight) that is already provided by all patients having surgery. Participants will have a peripheral intravenous catheter inserted, standard noninvasive monitors applied, supplemental oxygen administered via a nasal cannula or face mask, and positioned sitting. Intravenous midazolam and fentanyl will be titrated for patient comfort, while ensuring that patients remain responsive to verbal cues. The area of insertion will be sterily prepared and a clear, sterile, fenestrated drape applied. In the sitting position and with ultrasound guidance, after subcutaneous local infiltration with lidocaine‐ a 17g Tuohy and 5‐10 ml of saline with 1:200,000 epinephrine will be used to identify the correct plane, as defined by a hyperechoic shadow of the 10th transverse process and erector spine muscle immediately superficial. Once appropriate needle tip location is confirmed, a perineural catheter will be inserted under ultrasound guidance. This procedure will be repeated on the contralateral side. Following negative aspiration, 20 mL of 0.25% bupivacaine with 1:200,000 of epinephrine will be injected via both catheters with sonographic confirmation of local anesthetic spread. Blocks will be considered successful if, within 30 minutes, the participant experiences decreased sensation to cold temperature over the level of the ipsilateral 0 h thoracic dermatome at the level of anterior axillary line. Failed blocks/catheters will be successfully replaced or the participant withdrawn from the study. Treatment Group Assignment. The right‐sided catheter will be randomized to one of two treatment groups: bupivacaine 0.25% or normal saline ("study infusate"). The contralateral side will receive the other possible study infusate (either bupivacaine 0.25% or normal saline). Therefore, each participant will receive both treatments‐one on each side‐and act as their own control. Randomization will be stratified for benign vs. malignant surgical indication, in block sizes of 4. The randomization list will be created by the University of California San Diego Investigational Drug Service. Investigational pharmacists will prepare all study solutions as determined by the randomization list. Bupivacaine and normal saline are indistinguishable in appearance, and therefore investigators, participants, and all clinical staff will be masked to treatment group assignment for the duration of the enrollment and data collection period. Unmasking will not occur until statistical analysis is complete (termed "triple masking"). Study intervention. Perineural study infusate administration will be initiated within the operating or recovery rooms. Both infusion pumps will be programmed to deliver a basal infusion of 1 mL/h and an automatic intermittent bolus of 20 mL every 4 hours. This dose of bupivacaine is well‐within the standard maximum dose at our institution for perineural local anesthetic administration for other truncal locations such as the paravertebral space. No patient‐controlled bolus dose will be included. For any cases of inadvertent premature catheter dislodgement, the subject may opt to have the catheter replaced. Perineural catheters will be removed by healthcare providers upon study infusate reservoir exhaustion (approximately 50 hours) or just prior to hospital discharge‐whichever comes first. Postoperative analgesics. In addition to the perineural study infusate, subjects will receive standard‐of‐care oral and intravenous postoperative analgesics which can include acetaminophen, ibuprofen, gabapentin, and opioids (this is surgeon‐ and patient‐dependent). Therefore, all patients of this study‐regardless of the treatment arm they are randomized to‐will continue to receive current usual and customary analgesia: all will receive the same combination of acetaminophen, ibuprofen, gabapentin, opioids, and a single‐injection erector spinae plane block as they would regardless of study participation. Outcome measurements (end points). The investigators have selected outcome measures that have established reliability and validity, with minimal inter‐rater discordance, and are recommended for pain‐related clinical trials by the World Health Organization and the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement. All data collection will be through standard UCSD nursing/therapy EPIC notes and patient interviews in‐person during hospitalization or via a telephone call. All pain scores will be recorded for each side of the body (trunk) at each time point, measured using the Numeric Rating Scale. The overall objective of the proposed research is to determine the risks and benefits of adding a continuous erector spinae plane (ESP) block to a single‐injection ESP in patients undergoing open gynecologic surgery via a low transverse incision. Specific Aim 1: To determine the risks and benefits of adding a continuous ESP block to a single‐injection ESP the day following open gynecologic surgery. Hypothesis 1.1: Analgesia will be improved the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale ("average" pain included in the Brief Pain Inventory pain domain) [primary end point]. Hypothesis 1.2: Breakthrough pain will be decreased the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale ( w rst" pain included in the Brief Pain Inventory pain domain). Hypothesis 1.3: Pain during coughing will be decreased the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale. Specific Aim 2: To determine the risks and benefits on postoperative day 2 of adding a continuous ESP block to a single‐injection ESP following open gynecologic surgery. Hypothesis 2.1: Analgesia will be improved on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale ("average" pain included in the Brief Pain Inventory pain domain). Hypothesis 2.2: Breakthrough pain will be decreased on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale ("worst" pain included in the Brief Pain Inventory pain domain). Hypothesis 2.3: Pain during coughing will be decreased on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale. Analysis Approach Baseline characteristics by randomized side (bupivacaine to the left vs bupivacaine to the right) will be summarized with means, standard deviations, and quartiles. Balance between groups will be assessed. Specifically, standardized differences will be calculated using Cohen's d whereby the difference in means or proportions is divided by the pooled standard deviation estimates. Any key variables (age, sex, height, weight, and BMI) with an absolute standardized difference >0.78 (with 1.96×√(2/12.5)=0.78 [with a sample size of 25, the investigators expect about 12.5 randomized to left vs right]) will be noted and included in a linear regression model to obtain an estimate of the treatment effect adjusted for the imbalanced covariate(s). If residuals from the linear regression indicate violations of key assumptions (i.e. homoscedasticity or Gaussian distribution), data transformations and/or alternative generalized linear models will be applied as appropriate. If no imbalance is detected, the primary analysis will proceed by a one‐sample Wilcoxon test applied to the difference between paired observations (bupivacaine minus saline). Secondary outcomes will also be analyzed by one‐sample Wilcoxon test, or linear models (or generalized linear models) as appropriate to adjust for any imbalanced covariates. The primary analysis will exclude patients from the analysis if their low transverse incision is unexpectedly converted to a vertical incision following randomization. The investigators will compare the characteristics of these excluded participants compared to the primary analysis population, and also report results for the full intention‐to‐treat population (all randomized participants). Gatekeeping strategy Hypotheses will be tested with strong control of the familywise error rate at 5%. Testing begins with a single primary hypotheses H11. If this test is significant at the 0.05 level, that alpha is passed on to other hypotheses. For example, if the p‐value for H12 is less than 0.025, but the p‐value for H13 is not, then H13 can be tested at the 0.025 + 0.025/2 = 0.0375 level. If both H12 and H13 are rejected, no alpha is spent, and the investigators go on to similarly test H21, H22, and H23. If a given test does not reach local significance, alpha is spent and cannot be passed along to hypotheses. Simulated Power for NRS Power is estimated by simulations assuming a minimum clinically meaningful effect: NRS difference scores (bupivacaine minus saline, with negative scores favoring bupivacaine) are distributed with a median of ‐1 and interquartile range (IQR) ‐3 to 0. This IQR for a bilateral difference is consistent with unilateral IQRs (6 to 6 and 7 to 7) reported in Boules et al. (2020). A sample size of n=25 individuals would provide 84% power to detect such an effect with two‐sided α=0.05. Along with cancelled surgeries and drop‐out cases, the investigators anticipate requiring the consenting of 35 subjects to produce a data set consisting of a minimum of 25 subjects to be included i t e final analysis.

Nct (2021). "D9319C00001- 1L OC Mono Global RCT." ClinicalTrails.gov.
	This is a Phase III, randomised, double‐blind, placebo‐controlled, multicentre, international study assessing the efficacy and safety of maintenance olaparib compared with placebo in BRCAwt participants with Stage III to IV high grade serous or endometroid ovarian cancer (including fallopian tube cancer or primary peritoneal cancer) who are in complete or partial response following treatment with standard first‐line platinum‐based chemotherapy.

Nct (2021). "Desogestrel for the Preoperative Treatment of Endometrioma Compared With Placebo." ClinicalTrails.gov.
	Use of the oral desogestrel compared with placebo for preoperative treatment of endometrioma in the patient who underwent to surgery in next 3 months in Rajvithi hospital Patient will randomized in 2 group : Desogestrel and placebo After 1 months and 3 months the patient have to come to hospital to evaluate the result of study The result will be evaluated on cyst diameter, the associated pain and side effect of the oral desogestrel.

Nct (2021). "Diaphragmatic Breathing Exercises on Urinary Incontinence." ClinicalTrails.gov.
	Urinary incontinence (UI) is a chronic condition with involuntary urine loss. Urgency urinary incontinence (UUI) is a complaint of involuntary loss of urine associated with urgency; stress urinary incontinence (SUI) is a complaint of involuntary urine leaks out on effort or physical exertion including sporting activities, or on sneezing or coughing. In the mixed type of urinary incontinence (MUI) complaints coexist both in stress and urgency. Although urinary incontinence is not a life‐threatening condition, the feeling of discomfort caused by constant wetness, irritation, and the fear of odor affects the daily and social activities of in patients. The abdominal‐pelvic cavity contains most of the internal organs, is bounded by the diaphragm above, abdominal muscles anterior and lateral, thoracolumbar fascia and dorsal muscles in the back, and pelvic floor in the lower part. The respiratory diaphragm forms the roof of the abdomina‐pelvic cavity and the pelvic floor forms the base. The diaphragm is the main respiratory muscle, connected to the pelvic floor via the transversalis fascia. The pelvic floor supports internal organs, as well as constrictor and continence mechanisms of the urethral, anal and vaginal orifices in females. Musculofascial support is provided by the pelvic floor forms a hammock onto which the urethra is compressed during increases in intra‐abdominal pressure. When intraabdominal pressure increases, intra‐abdominal contents downward momentum is arrested by stretch resistance of the pelvic floor structures. At this time, the proximal intraabdominal portion of the urethra is compressed against the underlying supporting layer, which consists of the endopelvic fascia, vagina, and pelvic floor. Pelvic floor muscle (PFM) exercises, defined by Arnold H. Kegel, aims to regain support to the urinary organs by actively functioning the pelvic floor muscles. Previous researches show that PFM exercises are an effective treatment for UI and improve the quality of life (Qol) of in women. It is currently used as the first choice in conservative treatment of incontinence. However, PFM exercises may be encountered with some difficulties in order to understanding and performing by patients. Talas et al. showed that the pelvic floor moves in the craniocaudal direction parallel to the diaphragm during respiration. In this study, they suggested that during expiration, the pelvic floor muscles contract together with the abdominal muscles, pushing the abdominal organs up, pushing the intra‐abdominal pressure (IAP) to towards the diaphragm. In this study, the investigators hypothesized that the patients can improve pelvic floor function by performing DB exercises, indirectly via the facial and functional connection between the diaphragm and PFM, and incontinence could be reduced.

Nct (2021). "Differences in the Effectiveness of Electromagnetic Stimulation Therapy and Kegel Exercises Based on Compliance, Subjective - Objective Symptoms and Pelvic Floor Muscle Strength in Postpartum Stress Urinary Incontinence." ClinicalTrails.gov.
	We evaluate the compliance rate, effectiveness (UDI‐6 and 1‐hour pad test), and pelvic muscle strength of electromagnetic stimulation on stress urinary incontinence compared with Kegel pelvic floor muscle exercises in post‐partum women as conservative therapy. This was a Single‐blind randomized clinical trial in 40 post‐partum women diagnosed with stress urinary incontinence from at least three months post‐partum from March 2020 to February 2021 at YPK Mandiri Jakarta Hospital. We recruited consecutively for 40 patients divided into two groups based on type I error of 5% and type II error of 10%. The study population included all post‐partum patients diagnosed with SUI over three months. Subjects that are included were signed an informed consent form, post‐partum women aged 20 years or over with a diagnosis of stress urinary incontinence since three months post‐partum, found a urine leakage when coughing when the bladder volume was 200 to 250 ml, and was able to perform a pad test 1 hour. The study subjects were excluded if the subject complained of mixed incontinence, uncontrolled diabetes mellitus, grade 3 and 4 pelvic organ prolapse, chronic degenerative disease/trauma that affected muscle and nerve function, previous history of pelvic surgery, or a pacemaker. Then, the patients were randomly selected using a computer, namely simple randomization for treatment (Kegel muscle exercises or electromagnetic stimulation). Kegel exercises had to be done every day for eight weeks. The kegel exercise consisted of two types of training. The first one is contracting and relaxing the fast‐twitch muscle. Subjects contracted their muscle for two seconds and followed by four seconds of resting. The next part of the training was for slow‐twitch muscles. Subjects needed to contract their pelvic muscle for five seconds and followed by ten seconds rest. All of the training was done alone, five times/set and five sets/day. The time took for a session is approximately two minutes, and it took ten minutes to complete the exercise. To evaluate the patient's compliance, a self‐written control card and interview were used, with follow‐up every two weeks. Meanwhile, for those who received an electromagnetic stimulation chair, the patient sat on a magnetic chair with their perineum on the center allow the maximum effect of the magnetic field on the pelvic floor and sphincter muscles. We used NOVAMAG NT‐60 chair (NOVAMedtek, Turkey) for our electromagnetic stimulation regiment. The Electromagnetic stimulation consists of 15 sessions with 20 minutes duration and three times a week for five weeks. At the end of each session, subjects were also asked to fill out a control card as proof of attendance. Subjects that were unable to complete 80% of the intended therapy regiment would be classified as not compliant. Subjects' pelvic floor muscle strength was measured using Peritron by an obstetrician before and after the intervention. To measure their pelvic floor muscle, the patient was asked to contract the pelvic floor muscles and tightly hold for 2 to 3 seconds. Three experiments will be conducted with a break of 10 seconds between contractions, and the value taken is the highest measurement value. Physicians that evaluated the pelvic floor muscle strength will be blinded for the group allocation to reduce bias. The UDI‐6 questionnaire had been translated back and forth and validated. A reduction in the UDI‐6 score is treated as a positive result or an improvement of symptoms. 1‐hour pad test was used to evaluate their symptoms objectively. Based on the Committee International Continence Society (ICS), an increase of pad weight by 2‐10 grams classified as light SUI, 10‐50 grams as medium SUI, ≥50 grams as severe SUI. We evaluate all the subjects' symptoms before and after the therapy sessions. Physicians that evaluated the UDI‐6 and 1‐hour pad test will be blinded for the group allocation to reduce bias. The dropout criteria of both groups are subjects who do not fill out the control card for at lea one week consecutively. Patients are compliant when they attend or done 80% of the intended regimens of therapy. Subjects' characteristics were summarized using descriptive statistics. Parametric or Non‐parametric tests were done appropriately to the normality test of the sample. We used SPSS statistics 21.0 for data analysis and the cut‐off for statistical significance of 0.05.

Nct (2021). "Dissecting the IMpact of 11-OXygenated and Classic Androgens on Skeletal Muscle Insulin Sensitivity (DIMOXIS)." ClinicalTrails.gov.
	Androgen excess is the cardinal biochemical feature of polycystic ovary syndrome (PCOS). Serum testosterone correlates with insulin resistance in PCOS, however, there is an urgent need to improve our understanding of the association between androgens and the risk of type 2 diabetes. 11‐oxygenated steroids are the predominant androgens in PCOS and correlate closely with markers of insulin resistance. The bioactive 11‐oxygenated androgen 11‐ketotestosterone (11KT) binds and activates the androgen receptor with equal affinity to testosterone, yet nothing is known about its impact on metabolism or glucose homeostasis Crucially, there are no data linking androgen excess with muscle glucose metabolism and the differential contribution of 11‐oxygenated androgens to diabetes risk through these processes remains unknown. The investigators hypothesise the following: 1. Oral androgen exposure in women with PCOS results in distinct changes in tissue‐specific insulin sensitivity and muscle energy biogenesis 2. 11‐oxygenated androgen exposure exerts differential changes on the above parameters in comparison to classic androgen exposure The study has the following aims: 1. To examine the impact of oral androgen exposure on skeletal muscle insulin sensitivity and glucose disposal in women with PCOS. 2. To delineate the impact of androgen exposure on muscle mitochondrial function ex vivo in women with PCOS 3. To compare the differential impact of 11‐oxygenated androgen compared to classic androgens on glucose disposal and muscle mitochondrial function The two arms will run in parallel and all participants will undergo identical investigations before and after 7 days of either DHEA or 11KA4. Investigations will include baseline arthrometric measurements muscle biopsy, two‐step hyperinsulinaemic euglycaemic clamp, breath sampling. This interventional metabolic phenotyping study will probe the role of classic and 11‐oxygenated androgens in metabolic dysfunction in PCOS using gold‐standard in vivo metabolic phenotyping techniques. Delineating the distinct contribution of 11‐oxygenated androgens, through effects on skeletal muscle biology, to the risk of T2DM is an important step in the process of determining risk of type 2 diabetes in this vulnerable cohort.

Nct (2021). "Double Simultaneous Uterotonic Agents Versus Single Agent Regimen to Prevent Early Postpartum Hemorrhage." ClinicalTrails.gov.
	Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality in the world, accounting for a quarter of all maternal deaths globally. Most cases of PPH can be attributed to uterine atony, failure of the uterus to contract in the immediate postpartum period. Efforts to prevent uterine atony and thereby PPH have focused on active clinical management of the third stage of labor (the period between delivery of the infant and placenta) and the administration of uterotonic agents (medication that induces uterine contraction). Universal standard of care to prevent postpartum hemorrhage, according to the American College of Obstetrics and Gynecologists and World Health Organization includes various dose infusions of oxytocin. Additional uterotonics are given if necessary, according to noted blood loss and uterine tone. The best uterotonic(s), combination, route, and dose, however, remain actively debated. Randomized controlled trials have not proven that misoprostol is superior to oxytocin or methergine to treat postpartum hemorrhage, but it is a medication that is often used conjunctively or after other agents fail. A Cochrane review of treatment of primary postpartum hemorrhage revealed that oxytocin, ergot alkaloids (i.e., methergine), and combined oxytocin‐ergot alkaloid administration were equally effective in preventing PPH in the general obstetric population, whereas prostaglandins alone (i.e., misoprostol) were not. In an effort to determine the benefit of a simultaneous double uterotonic agent regimen in the prevention of PPH, the investigators propose to conduct a controlled trial in which women will be randomly assigned to an intervention group (buccal misoprostol and intravenous oxytocin administered simultaneously) versus a control group (standard of care, intravenous oxytocin alone).

Nct (2021). "Dual Trigger for Elective Fertility Preservation." ClinicalTrails.gov.
	Elective oocyte cryopreservation (EOC) has been gaining increasing importance in the last few years, driven by the widespread information regarding the concept of 'age‐related fertility decline', as well as the availability of efficient contraception and women's increasing educational and professional aspirations. Considering the similar clinical outcomes regarding live birth rate after vitrified‐warmed and fresh oocytes and the proven cost‐effectiveness of this approach, oocyte banking is now considered an efficient technique in assisted reproduction. Previous studies have shown that both patient's age and the number of oocytes retrieved have a significant impact on the cumulative live birth rate (CLBR) in patients undergoing EOC, highlighting the importance of maximizing oocyte yield in these patients. In all these former reports, final follicular maturation was triggered by one bolus of human chorionic gonadotropin (hCG) or, following recent trends in clinical practice, by a single bolus of Gonadotropin Releasing Hormone agonist (GnRH‐a). More recently, the concomitant administration of both GnRH‐a and a bolus of HCG prior to oocyte retrieval (dual trigger) has been proposed as a new strategy for final follicular maturation, aiming to improve oocyte and embryo quality . When compared to HCG trigger, the dual trigger adds the more physiologic follicular stimulating hormone (FSH) and luteinizing hormone (LH) peak provided by GnRH‐a. With this approach, several studies have reported an increase in the number of MII oocytes retrieved, as well as in the number of good quality embryos and improved pregnancy outcomes in different subpopulations of infertile patients. Nowadays, the standard of care in patients undergoing a freeze‐all approach, either for oocyte or embryo cryopreservation, is final follicular maturation with GnRH‐a due to its more physiologic and shorter surge of both LH and FSH, terminating 24h after its onset, and reducing the risk of ovarian hyperstimulation syndrome (OHSS). So far, no study has compared the dual trigger approach to the use of a single bolus of GnRH‐a. By adding HCG activity and, therefore, generating higher intracellular cyclic adenosine monophosphate (cAMP) accumulation, an amplification of the steroidogenic response of the pre‐ovulatory follicle might be achieved with the dual trigger when compared to the GnRH‐a trigger alone. Therefore, the investigators set out to perform this randomized controlled trial aiming to compare, for the first time, the dual trigger and the GnRH‐a trigger regarding the number of MII oocytes retrieved in patients undergoing EOC.

Nct (2021). "A Dyadic Approach to Perinatal Depression in Primary Care: maternal Infant and Dyadic Care." ClinicalTrails.gov.
	Eligible and consenting participants will be randomized in a single blind manner (research visitor will be blinded to condition) at a 1:1 ratio to either MInD (parenting intervention and usual perinatal collaborative care) or usual collaborative care in their second trimester of pregnancy. Research assessments will be administered during pregnancy and post‐partum.

Nct (2021). "Education in Patients With Persistent Pelvic Pain." ClinicalTrails.gov.
	In this intervention, the effects of implementing educational programs in patients suffering from pelvic persistent pain will be assessed. Patients with pelvic persistent pain have both problems directly related with their pain and other issues that appear derived from suffering pain over a determined period, such as alterations in the sexuality or overall quality of life. Facing these patients is a challenge for professionals, and many can't find the treatment that properly fits the patient's clinical presentation. Education, and educating patients on their problem, is an exponentially growing alternative used in Physical Therapy involving patients who suffer from a dysfunctional pain, chronic pain, or any kind of pain presentation that affects the patient's well‐being. This study will assess firstly if the implementation of a pain‐related education program is relevant in the treatment of pelvic persistent pain, and will further observe which modality (presential workshops or online‐accessed material) is the most effective involving adherence and improvement.

Nct (2021). "Effect of Acupuncture on the Clinical Outcome of IVF-ET in Patients With Recurrent Implantation Failure." ClinicalTrails.gov.
	In the field of assisted reproduction techonology, there are still 10% of patients with recurrent implantation failure. In order to explore the effect of acupuncture on the clinical outcome of IVF‐ET in patients with recurrent implantation failure, the patients divide into the experimental group or the control group. In the experimental group, those patients undergo acupuncture at the beginning of embryo transfer cycle three times a week until 14 days after embryo transfer. In the control group, those patients do not receive any treatments during embryo transfer cycle. Both of two group patients are checked including endometrial receptivity index and fill in SAS anxiety scale form. Statistical analysis of the two groups of primary endpoint (clinical pregnancy rate) and secondary endpoint (embryo implantation rate, biochemical pregnancy rate, early pregnancy loss rate, ongoing pregnancy rate, live birth rate)are done.

Nct (2021). "The Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota." ClinicalTrails.gov.
	Study question: Does antibiotic alone or in combination with live biotherapeutic treatment of an abnormal vaginal microbiota improve the reproductive outcomes of IVF couples? Study hypothesis: The investigator hypothesize that treatment of the reproductive tract pathogens and restoration of vaginal Lactobacillus will improve the reproductive outcomes of IVF patients. What is known already? Ultra‐deep sequencing methods enable the refinement of reproductive tract microbiology in infertile patients. A recent meta‐analysis reported that 19% of infertile patients had abnormal vaginal microbiota Moreover, someone have detected the presence of a Gardnerella (G.) vaginalis dominated endometrial biofilm in 50% of non‐infertile patients with abnormal vaginal microbiota undergoing curettage; thus the treatment of such an endometrial biofilm might play an important role for the endometrial receptivity and subsequently the clinical pregnancy rate. Pilot study: In a recent pilot study it was observed that an abnormal vaginal microbiota negatively affects the clinical pregnancy rate in IVF patients. In this study the prevalence of abnormal vaginal microbiota was 28% (36/130) and only 9% of patients with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (p=0.004). This association remained significant in an adjusted analysis. Furthermore, the invetigators have preliminary results demonstrating that vaginal bacteria such as G. vaginalis can be found in the endometrium of IVF patients, which is also supported by recent publications What is the novelty of this study? To the investigators knowledge, no previous treatment study of abnormal reproductive tract microbiota has been performed in IVF patients; this relatively small intervention holds the potential to increase the baby‐take‐home rate after IVF treatment.

Nct (2021). "Effect Of Cryolipolysis On Visceral Adiposity Index In Polycystic Ovarian Syndrome Patients." ClinicalTrails.gov.
	This study will be carried out on sixty females with polycystic ovarian syndrome (PCOS) who were selected from the Outpatient Clinic of Gynecology at Qasr Al Aini University Hospital. Their age ranged from 17‐28 years, body mass index was 25‐30 Kg/m2. They experienced hyperandrogenism, hyperinsulinemia and amenorrhea not less than 6 months. PCOS females will be randomly assigned into two equal groups: group (A) (control group) consisted of 30 women who received low caloric diet (1200 Cal/day) and group (B) (study group) consisted of 30 women who received the same diet regime and cryolipolysis

Nct (2021). "The Effect of Diet on Parents' Mental Health in the Postnatal Period." ClinicalTrails.gov.
	The study will employ a between‐groups, randomised, controlled, participant‐blind design. The study will primarily recruit mothers of infants under 6 months old to take part. Participants will be invited to an online study investigating diet and mental health and will be provided with an information sheet detailing what the study entails. If participants would like to take part, they will be sent a weblink to the online study. Participants will be randomly assigned to either the intervention (consumption of high flavonoid food items) or the control (no change to diet) condition. Only the experimenters will know which group participants have been assigned to to prevent participants unconsciously biasing results. The online study will be hosted on Jisc online surveys. Once participants open the study weblink, they will be presented with the study information sheet followed by a consent form. Once participants have consented to take part, they will be asked to provide some demographic information about themselves (e.g. age, occupation, health or psychological diagnoses, any pregnancy or birth complications) and their baby (e.g. age, sex, health diagnoses, breast or bottle feeding). Mothers will then complete PANAS‐NOW, EPDS, PSAS, WHOQOL, STAI and FFQ measures. Once completed, they either will (if in high flavonoid group) or will not (if in control group) be presented with a high‐flavonoid food list and instructions for food consumption over the 2 week intervention. Those presented with the high flavonoid food list will be encouraged to consume 2 high flavonoid food items per day from the list over the next 2 weeks, above what they already consume each day typically. Both intervention and control groups will be encouraged to fill in food logs where they will write down all food consumption every day over the 2 week period. One and a half weeks into the intervention study participants will be reminded (via email) to complete the follow up questionnaires via a weblink when convenient for them over the next few days. They will then complete the online questionnaires (PANAS‐NOW, EPDS, PSAS, WHOQOL, STAI and FFQ) via the weblink at the end of the dietary intervention (day 14). Upon completion, participants will be presented with a debrief sheet explaining the aims of the study, what the study entailed and which condition they were in. Participants will also be reminded of their right to withdraw their data from the study if they wish. Helplines and support weblinks will be provided to all participants as well as encouragement for participants to contact their GP should they wish to seek support. Alongside recruitment of postnatal mothers, fathers will also be invited to take part in the study, recruited via the mothers that consent to take part. This is so that important pilot data can be collected on a sub‐sample of postnatal fathers to assess mood outcomes in this at‐risk population before and after a 2 week dietary flavonoid intervention. This will follow the same methods, procedures and measures as recruited mothers. The study aims to recruit 80 postnatal mothers. A power analysis using GPower 3.1 rendered a total sample size of 40 as appropriate to obtain a small effect (0.3) at a power of 0.95 and alpha level of 0.05. The recruitment aim will be 80 to allow for a number of participant dropouts and to allow sufficiently powered analysis between groups at baseline. An additional aim is to recruit a sub‐sample of 20 postnatal fathers alongside the main study recruiting mothers. This is to collect important pilot data to assess whether similar or different patterns or outcomes occur in a postnatal male population to inform future research into dietary intervention in men.

Nct (2021). "Effect of Electro-acupuncture on Women With Diminished Ovarian Reserve." ClinicalTrails.gov.
	First, patients will be recruited according to the inclusion criteria and exclusion criteria. Second, baseline measurements (including ovarian reserve function, blood biochemical index, scores from the self‐rating anxiety and depression scale, quality of life) will be taken. Third, each patient will receive 24 sessions of acupuncture in 2‐3 months, twice or three times a week. Last, the above baseline measurements will be taken again as soon as the treatment is finished and outcome measures will be recorded after the treatment.

Nct (2021). "Effect of External Electrical Stimulation and Pelvic Floor Muscle Training." ClinicalTrails.gov.
	Fifty one women with mild and moderate SUI symptoms were included in the study. The patients were divided into three groups of PFMT (n:17), EES (n:17) and PFMT+ EES (n:17) by block randomization. The PFMT was applied every day of the week, and EES was applied 3 days a week for 8 weeks. Pelvic floor muscle strength (PFMS), pelvic floor muscle endurance, subjective perception of improvement, severity of incontinence, quality of life, pelvic floor dysfunction (PTD) and urinary parameters were assessed as outcome variables. All measurements, except subjective perception of improvement were investigated before and after treatment.

Nct (2021). "Effect of Extracorporeal Shock Therapy for Dysmenorrhea." ClinicalTrails.gov.
	Patients with primary dysmenorrhea diagnosed by a physician, spondylolisthesis and chronic low back pain were excluded from the study. They were randomly assigned into two equal groups (A& B). Group (A) consisted of twenty subjects, with an average age 29.2±1.9Yrs, and BMI 27.28±2.1kg/m2 who received Extracorporeal shock waves. Group (B) consisted of twenty patients, with an average age 28.58±2.2Yrs, and BMI 28.92±0.7kg/m2 who received sham technique. A hot pack was used for 15 minutes for both groups (A&B) before the treatment.

Nct (2021). "The Effect of Health Education and Progressive Muscle Relaxation Exercise on Vasomotor Symptoms and Sleep Problems With Perimenopausal Women." ClinicalTrails.gov.
	Purpose and type of study The study examines the effects of health education and progressive muscle relaxation exercise (PMRE) on vasomotor symptoms and sleep problems in women in the perimenopausal period; pretest‐posttest is a randomized controlled, factorial group experimental study. Universe and sample The research was conducted in a family health center. The required institutional permission and ethics committee approval was received. The universe of the research consists of 1830 women between the ages of 40‐55 registered at Gazi Family Health Center. A pilot application was conducted to determine the sample size in the study. Power analysis was performed using the G * Power 3.0.10 program with 18 women (PMRE + Health education group (n = 6), PKGE group (n = 6), control group (n = 6)) who took part in the pilot study. According to the power analysis performed by calculating the effect size (0.177), the sample size calculated with 90% power and 5% margin of error; A total of at least 84 women were identified, including 28 women in the PMRE + Health education group, 28 women in the PMRE group and 28 women in the control group. Similar to our study, 36 women were included in each group in our study by calculating the drop‐out rate in the study of Garcia et al. (2018) (Garcia et al., 2018). The data collection process of the research started on 17.02.2019 and the determined sample number was completed on 02.04.2020. In this process, women who applied to ASM between 17.02.2019‐23.01.2020 and who met the sampling criteria and accepted to participate in the study after the purpose and importance of the study were explained were determined. Under the direction of the researcher, the women interviewed a nurse independent of the study. Nurse The inclusion criteria used the check‐list form to evaluate the compliance of the women with the research criteria. Personal information form, vasomotor symptom VAS and Women's Health Initiative Insomnia Scale‐WHIIRS (pre‐tests) were applied to determine compliance with the criteria. After the women meeting the criteria were informed about the study and consent was obtained, randomization was performed. During the study, a total of 482 women who applied to family health center were interviewed. Of these women; non‐perimenopausal (n = 20), surgical menopause (n = 17), using psychiatric drugs and sleeping pills (n = 62), using alcohol (n = 14), women health initiative insomnia scale score below 10 (n = 78), the severity score of VAS symptoms for vasomotor symptoms is less than 3 (n = 69), who received hormone replacement therapy (n = 27), the number of moderate and severe hot flashes per day (n = 67), and A total of 374 women who did not agree to participate in the study (n = 20) were not included in the study. A total of 108 women who met the research criteria were stratified according to their smoking and regular exercise status. After stratification, women were assigned to the groups by simple randomization method (closed envelope method). For this purpose, three different envelopes were formed by placing the cards with A, B and C in the envelopes. A: PMRE + Health education group, B: PMRE group, C: represent the control group. In order to prevent bias and hide randomization, random assignments were made to the groups by the nurses using the closed envelope method. According to the envelope result, women were included in the PMRE + Health education group, the PMRE group and the control group. The study sample included women in the PMRE + Health education group (n = 36), the PMRE group (n = 36), and the control group (n = 36). Women participated in the practices prepared for the groups they were included in. Six of the women in the PMRE + Health education group participated in the training, but were excluded from the sample due to moving (n = 2), death of a relative (n = 1), illness (n = 1) and not doing PMRE in sufficient numbers (n = 2). Six of the women in the PKGE group participated in the training, but were excluded from the sample due to the death of the relat e (n = 1) and the illness (n = 2) not making PKGE sufficiently (n = 3). Six women in the control group were excluded from the sample because they would voluntarily (n = 4) and start a new job (n = 2). As a result; A total of 18 women included in the sample left the study, the study was completed with women in the PKGE + Health education group (n = 30), the PMRE group (n = 30), and the control group (n = 30). At the end of the research; As a result of the power analysis made using the G * Power 3.0.10 program; At least 90 women in total were found to be sufficient with 90% power, 5% margin of error and 0.172 effect size.The data was collected using personal information form, Visual Analogue Scale for Vasomotor Symptoms (VAS), Women's Health Initiative Insomnia Rating Scale‐WHIIRS, vasomotor symptom diary, progressive muscle relaxation exercise follow‐up schedule, and health education practice follow‐up schedule. Randomization In our study, support was received from a statistician during the randomization phase. The stratified sampling method was applied over these two prognostic factors to ensure randomization, as it is thought that smoking (smoker and non‐smoker) and regular exercise (regularly exercising and not exercising regularly) may affect our study results. After stratification; A total of four groups were determined according to the layer properties. Four stratum groups were formed to ensure equal distribution of women in terms of smoking and regular exercise in the experimental and control groups in the study. The closed‐envelope method was used to assign stratified women to the control and experimental groups without being biased, and an equal number of women were assigned to each group. During the preparation of envelopes, opaque envelopes are used to prevent the inside of the envelope from being seen from the outside. The envelopes were created by a nurse working at the Family health center, independent of the research. Three different envelopes were formed by placing the cards A, B and C in the envelopes. A: PMRE + Health education group, B: PMRE group, C: represents the control group. In order to prevent bias and conceal randomization, women were randomly assigned to the groups by a sealed envelope method by a second nurse working at family health center outside the researcher. The nurse placed women who met the research criteria in the appropriate strata from four strata. When groups of three people were formed in each stratum, the women from the strata were assigned to the groups as follows. He asked the first woman with the same characteristics to come to each stratum group to pull one of the three envelopes marked A, B, and C. For example: If C is in the envelope, the first woman who came was assigned to the control group. For the second woman, she was asked to pull one of the two envelopes, this time marked A and B. If A was placed in the draw, the second woman was assigned to the PMRE + Health education group. The envelope was not drawn for the third woman who came, and she was assigned to the last remaining group, the PMRE group. The same method was applied for all three women in the same layer after that. Thus, 108 women in the sample were randomly assigned to the PMRE + Health education group, the PMRE group and the control groups stratified and equally. Until the initiatives started, the groups to which the women were assigned were not known to the researchers. The homogeneity of the randomized groups was compared with the chi‐square test and it was found that there was no statistical difference between the groups in terms of stratification criteria, and the groups were homogeneous. Prevention of bias In the study, women in the PMRE + Health education group and the PMRE group could not be blinded because they will participate in the training. In order to prevent bias, women were informed, assigned to groups and data were collected by a nurse outside of the study. However, the study was carried out by the researcher because the research was a thesis study, the number of application gro s was high, multiple attempts were applied and the application should be done by an experienced researcher. For these reasons, the researcher could not be blinded. Prevention of bias in the research (in terms of data collectors, statistician and reporting) has been done. The pre and post‐tests were filled by a nurse independent of the research. The collected data were coded as A, B and C groups by the researcher in a package program called SPSS (IBM SPSS Statistics 24). The analysis of the data coded in terms of groups was done and reported by a statistician. In this way, detection bias, statistical bias, and reporting bias were controlled. Data collection and application process 1. st evaluation (conducted in the 1st week) The women who applied to the family health center and met the sampling criteria and accepted to participate in the study after the purpose and importance of the study were explained were determined. The women were informed about the research by the nurse with the direction of the researcher. Nurse 'The inclusion criteria used the check‐list form to evaluate the compliance of the women with the research criteria. It was ensured that women filled the personal information form, vasomotor symptom VAS and Women's Health Initiative Insomnia Scale, which are necessary to determine compliance with the criteria. The nurse placed the women who met the criteria in the appropriate strata from four strata. When groups of three people were formed in each stratum, women were assigned to the groups as follows. He asked the first woman with the same characteristics to come to each stratum group to pull one of the three envelopes marked A, B, and C. For example; If C is in the envelope, the first woman arriving was assigned to the control group. For the second woman, she was asked to pull one of the two envelopes, this time marked A and B. If A was placed in the draw, the second woman was assigned to the PMRE + Health education group. The envelope was not drawn for the third woman who came, and she was assigned to the last remaining group, the PMRE group. The same method was applied for all three women in the same layer after that. Thus, women were randomly assigned to the study groups. Following this, a vasomotor symptom diary was given to all women by the nurse. The women assigned to the PMRE + health education group and the PMRE group were asked to complete the vasomotor symptom diary every day for a week until a training class would be established one week later and up to this training class. The women in the control group were instructed to fill in the vasomotor symptom diary until the end of the study. The averages in the diary filled in the first week of all women formed the baseline data before starting the study. Establishment of PMRE + health education and PMRE education classes (1st week was held) When small groups of 3 people are formed in the stratification groups and 3 women are appointed to the working groups, by taking name lists from the nurse; The researcher interviewed women. In these meetings; An explanation and planning were made for the groups to be intervened about the training day, place, time, duration, and wearing appropriate/comfortable clothes. At the beginning of the second week of the study, a time frame between 13.00‐16.00 was determined to be suitable for the researcher and all three women in his group. In PMRE + Health education and PMRE group, training was given in groups of three (12 groups + 12 groups = 24 groups). The application was made in a room allocated for research in the family health center. This room is quiet, dim, and spacious. There are seats and a table for women and the researcher. Considering the capacity of this room, it was decided that it would be appropriate for the groups to have three people in order for women to participate in health education more actively and the researcher could observe each woman performing PMRE in detail. The women were asked to attend the training in comfortable clothes and not to be very hungry or full. The hall is pre‐ventilated or the application and the application environment has been prepared. In order not to be disturbed during the application, a warning letter is hung on the door. Participants were offered water during the training sessions, tea, chocolate, sweets, dried fruits, cakes, etc. after the application. Training the PMRE + health education group (2nd week) Each group was provided with health education (training on vasomotor symptoms and sleep hygiene) and PMRE practice training. Health education (training on vasomotor symptoms and sleep hygiene) lasted approximately 30 minutes. Then, the gradual muscle relaxation exercise was performed by the researcher in line with the musical instruction prepared by the Turkish Psychologists Association (01.01.2010) for 30 minutes. After an interval of approximately 10 minutes, PMRE was performed by women for approximately 30 minutes. The training started with health education (training on vasomotor symptoms and sleep hygiene). The researcher will spend about 30 minutes with a slide show prepared in accordance with the content of the educational guide. He gave training. During and after the training, questions from women were answered, women's own experiences were shared, and they were talked about how to apply education to their daily lives. The questions of women who were hesitant about this issue or who thought they might have trouble at the point of the application were answered. Participants in the training were given a booklet titled "A Guide to Coping with Hot Flashes, Night Sweats, and Sleep Problems Frequently Encountered in the Transition to Menopausal Period" prepared by the researchers. At the end of the training, the women were asked to apply the topics of health education to their daily lives as much as possible every day for 8 weeks, if not at least 4 days a week. It was stated that those who do not comply with this program will be excluded from the sample. The researcher first demonstrated the PMRE application by doing it himself and then enabled the participants to practice. All participants were observed by the researcher during the learning process and they were ensured to apply progressive muscle relaxation exercises correctly. At the end of the exercise, the women were asked to do relaxation exercises every day if possible for 8 weeks, at least 4 times a week when this was not possible, before going to sleep at night. The musical instructions for the gradual relaxation exercise were uploaded to the phones of all women. Feedback was obtained from the women after the first exercise alone and the questions were answered. Thus, women were provided to do the application correctly. A Whatsapp® group was established for each 3‐person training group in order to monitor and encourage women to exercise health education and exercise. The women were asked to report from this group when they adapted their health education to their daily lives and after applying the exercise. Throughout the study, the women were reminded to adapt health education and exercise every day from the Whatsapp® group, and women who did/did not practice the application were identified with their feedback. At the end of the training given by the researcher, the women were given a vasomotor symptom diary, PMRE follow‐up chart, and health education follow‐up chart to fill in until the end of the study. Women marked their practices on the health education follow‐up chart and progressive muscle relaxation exercise follow‐up chart for 8 weeks. This marked chart was retrieved from the participants at the end of the 8‐week practice. 2. nd evaluation (made in the 5th week) Four weeks after the PMRE + health education, women were made to fill the Women's Health Initiative Insomnia Scale and the visual analog scale for vasomotor symptoms for the second time by the nurse. They were reminded to continue filling out the diary and charts until the research was completed. 3. rd evaluation (conducted at the 9th week) 8 weeks after the PMRE + health education, the nurse was asked to fill the Women's Health Initiati Insomnia Scale and the visual analog scale for vasomotor symptoms for the third and last time. The diaries and charts they filled out were taken and filed, and the research was terminated. The data were collected as specified in the application calendar. Training the PMRE group (2nd week) Only women in the PMRE group were taught how to perform PMRE. Approximately 30 minutes, the gradual muscle relaxation exercise was applied by the researcher in accordance with the musical instruction prepared by the Turkish Psychological Association (01.01.2010). Then, women were allowed to apply PMRE for approximately 30 minutes. All participants were observed by the researcher during the learning process and they were ensured to apply progressive muscle relaxation exercises correctly. At the end of the exercise, the women were asked to do relaxation exercises every day if possible for 8 weeks, at least 4 times a week when this was not possible, before going to sleep at night. The musical instructions for the gradual relaxation exercise were uploaded to the phones of all women. Feedback was obtained from the women after the first exercise alone and the questions were answered. Thus, women were provided to do the application correctly. In order to monitor and encourage women to do PMRE, a Whatsapp® group was established for each 3‐person training group. The women were asked to report from this group after applying the exercise. Throughout the study, women were reminded to do the exercise every day, and women who did/did not do it were identified with their feedback. At the end of the training given by the researcher, the women were given a vasomotor symptom diary and PCI follow‐up chart to fill in until the end of the study. Women marked their practices on the Progressive Muscle Relaxation Exercise Follow‐up Chart for 8 weeks. This marked chart was retrieved from the participants at the end of the 8‐week practice. 2nd evaluation (conducted at the 5th week) Four weeks after the training, women were made to fill the Women's Health Initiative Insomnia Scale and the visual analog scale for vasomotor syndromes for the second time by the nurse at the Family health center. They were reminded to continue filling out the diary and charts until the research was completed. 3rd evaluation (conducted at the 9th week) 8 weeks after the training, women were provided to fill the Women's Health Initiative Insomnia Scale and the visual analog scale for vasomotor symptoms for the third and last time by the nurse at the family health center. The research was concluded by taking the diary and charts they filled out. The data were collected as specified in the application calendar. Control group 1. st evaluation (conducted in the 1st week) In the first evaluation, women were made to fill in the personal information form, vasomotor symptom VAS, and the Women's Health Initiative Insomnia Scale. After the pre‐tests were applied, random assignments were made to the groups. Following this, a vasomotor symptom diary was given to women in the control group by the nurse. They were instructed to fill in the vasomotor symptom diary until the end of the study. No intervention was applied to the women assigned to the control group as a result of randomization. 2. nd evaluation (conducted at the 5th week) The nurse made it possible for women to fill the Women's Health Initiative Insomnia Scale for the second time and the visual analog scale for vasomotor symptoms. They were reminded to continue filling in the diary until the end of the study. 3. rd evaluation (conducted at the 9th week) women were provided to fill the Women's Health Initiative Insomnia Scale and the visual analog scale for vasomotor symptoms for the third and last time by the nurse. The research was terminated by taking the diaries they filled. The data were collected in accordance with the application schedule. The data were stored in the SPSS 24 program. In the analysis of the data, ANOVA test, Repeated Measures test, Kruskal‐Wallis H test, Friedman test, and χ2 test statistics were use

Nct (2021). "The Effect of IVF Counseling on Psychosocial Well-Being." ClinicalTrails.gov.
	The study will be conducted in the Infertility clinic of a medical school hospital. The study included women receiving IVF treatment. In the pre‐initial evaluation, "Introductory Information Form, Screening on distress in fertility treatment (SCREENIVF), Infertility Stress, Life Quality Scale for Persons with Fertility Problems(FertiQol), Subjective Units of Distress Scale‐SUD application is planned. A "Consultancy Program" will be applied to the experimental group in the form of two modules in addition to drug applications, egg pick up and embryo transfer before, during and after clinical routine health care. The first module of the counseling program is the definition of infertility, the treatment process, its effects on the life process and coping methods. The second module includes the application of breath awareness and Emotional Freedom Technique (EFT) within the scope of coping methods with infertility stress. Emotional Freedom Technique‐EFT is an energy psychotherapy based on the principle that each limiting thought, disturbing emotion and memory of an individual disrupts the energy flow in the body and creates congestion. This technique, the stimulation on the meridian system by focusing on the thought, disturbing emotion or memory that prevents the individual (often by touching) regulates the energy flow and provides the individual to relax. With breath awareness, beneficial results can be obtained, such as physical, sensory and mental control, life‐facilitating techniques, individual and social awareness, re‐existence and raising the level of consciousness. Within the scope of the counseling program, a total of seven follow‐ups will be made, five‐to‐one, via two phone calls. On the day of follicle development (2nd Follow‐up), Egg Pick up Procedure (4th Follow‐up) and Embryo transfer (5th Follow‐up), the patient will be given breathing exercises and EFT and Subjective Units of Distress Scale will be scored. The control group will continue clinical routine health care and will be followed up on the first day of IVF treatment (1st follow‐up) and on the seventh day of embryo transfer (2nd follow‐up). For ethical reasons, a consultancy program will be applied to the control group after the second follow‐up. Data collection tools will be applied again to both groups in the final evaluation.

Nct (2021). "Effect of Laughter Yoga Therapy on Postpartum Depression." ClinicalTrails.gov.
	Laughter yoga sessions, stretches and stretches, songs, clapping and body It starts with light warm‐up techniques that include movements. These are to break down all kinds of inhibitions and It is aimed at developing the feelings of childlike play. breathing exercises lungs they are ready to laugh and are combined with the following series of laughing exercises. LY In order to provide group dynamics in therapy, the group should consist of at least 5‐12 people. provided. Real laughter is often experienced during laughter meditation; it's contagious and may trigger laughter in other people in the group, hence the group can establish greater connections with its members. Laughter yoga sessions are always held at the same time and in the same place to encourage the participation of individuals. has been done. Therapy sessions are between 40‐45 minutes. Sessions started on time and was completed on time. In the research, a total of 6 sessions of laughter, once a week, yoga was done. The experimental group was interviewed in an online meeting prepared by a certified LY trainer. She received LY exercises once a week (40 minutes per session) for 6 weeks (6 sessions). Each The meeting was organized with a maximum of 12 people.

Nct (2021). "Effect of Physical Activity and Pain Education on Endometriosis-associated Pain." ClinicalTrails.gov.
	Due to the complexity of the disease, international clinical guidelines recommend that the treatment of endometriosis‐associated pain should come from a multimodal and multidisciplinary perspective. Numerous non‐pharmacological treatments have been proposed to alleviate endometriosis‐associated pain, such as physical activity. Physical activity was introduced as a factor in the treatment of endometriosis‐associated pain over three decades ago, with the possible beneficial effect that physical activity stimulates anti‐inflammatory properties that will impede the development of endometriosis and lower the pain. A recent systematic review and meta‐analysis found one randomized controlled study that showed no effect of physical activity on endometriosis‐associated pain. They concluded that the methodological quality of this study was low, and the need for future randomized controlled studies was warranted. We, therefore, aimed to study the effect of pain education and group‐based physical activity versus pain education alone on women with endometriosis‐associated pain.

Nct (2021). "Effect of Progesterone on Latent Phase Prolongation in Patients With Preterm Premature Rupture of Membranes." ClinicalTrails.gov.
	After taking informed written consent, the recruited patients will be subjected to the following: 1. Detailed history ‐ Personal History: Name, age ,residence ,special habits of medical importance ‐ Obstetric history: first day of last menstrual period for accurate estimation of gestational age and antenatal care ‐ Past history: history of any medical disorder or surgical history with particular emphasis on prior PPROM or preterm labor ‐ History of the present pregnancy: Medical or surgical condition to define high risk pregnancy. 2. Examination of the patients General examination: blood pressure, pulse, temperature Abdominal examination: ‐ Inspection: fundal level, scars, umbilicus. ‐ Palpation: presence of contractions, fetal lie and presentation. ‐ Pelvic Examination only by sterile speculum to exclude cord prolapse , bloody liquor and cervical dilatation and effacement ‐ Non stress test to ensure reassuring fetal well being ‐ Ultrasound examination to:‐ ‐ Assess fetal viability. ‐ Amniotic fluid index. ‐ Determine gestational age. ‐ Exclude major anomalies. ‐ Placental location. 3. Baseline laboratory investigations: ‐ Complete blood count (CBC). ‐ Prothrombin time (PT). ‐ Activated partial thromboplastin time (aPTT). ‐ Liver and kidney function. The included patients were randomized using sealed opaque envelope method into one of two groups: Group I (study group): in which 17‐hydroxyprogesterone caproate (17P) (250 mg in castor oil, 1 mL total volume, intramuscular injection weekly) will be administered. Group II (control group): in which an identical‐appearing placebo (1 mL castor oil only) will be administered.

Nct (2021). "The Effect of Progressive Muscle Relaxation and Laughter Therapy on Women Undergoing In Vitro Fertilization." ClinicalTrails.gov.
	Infertility, one of the important components of reproductive health, affects one in four couples in developing countries.The emergence of assisted reproductive techniques such as in vitro fertilization (IVF) gives infertile couples the opportunity to have both pregnancy and a baby. Couples are affected emotionally during IVF treatment and women experience more problems than men. The majority of women experience emotional problems such as anxiety and depression because of infertility, invasive treatment procedures, physiological effects of gonadotropin stimulation and positive outcome expectation.Considering the effect of anxiety and depression on infertile women, it is important to examine the effectiveness of progressive muscle relaxation exercises and laughter therapy as complementary therapy in psychosocial care.

Nct (2021). "The Effect Of Reiki And Massage With Sage Oil On Primary Dysmenorrhea." ClinicalTrails.gov.
	This study was a randomized controlled trial. It included young girls with primary dysmenorrhea in a district located in the south of Turkey and was conducted between March 01, 2021 and June 30, 2021. The sample size of this research was decided by performing a power analysis in the power statistical program. Considering the parameters of the groups, the effect size was calculated to be 0.5003604. Since α was found to be 0.05 and power (1 ‐ β) was 0.95, a total number of 66 participants were distributed into three equal groups (sage oil massage: 22, Reiki: 22, control: 22). Considering the possibility of case losses, 30 participants were included in each group; finally, a total of 90 people were included in the study. For data collection, a questionnaire regarding sociodemographic characteristics and the visual analog scale (VAS) were used. Reiki and massage with sage oil were applied for 30 minutes, and no application was performed on the control group.

Nct (2021). "The Effect of Tele-Health Education Provided in the Postpartum Period in the Covid 19 Pandemic." ClinicalTrails.gov.
	In the planned study, it was aimed to examine the effect of tele‐education offered in the postpartum period in the covid 19 pandemic on the levels of depression, attachment and anxiety of women.

Nct (2021). "Effect of Thumbtack Needle on Ovarian Function of Women With Diminished Ovarian Reserve (DOR)." ClinicalTrails.gov.
	Diminished ovarian reserve (DOR) is the precursor state of ovarian failure, and can cause the decline of women's reproductive function. Some studies have demonstrated that acupuncture can improve ovarian function. Thumbtack needle, as a kind of acupuncture, has been found effective in treating DOR in our clinic. In this trial, the investigators Using a multi‐center, large sample, randomized, controlled and blind clinical trial to evaluate the effect of thumbtack needle on ovarian function of patients with diminished ovarian reserve (DOR). First, patients will be recruited according to the inclusion criteria and exclusion criteria. Second, baseline measurements (including ovarian reserve function, blood biochemical index, scores from the self‐rating anxiety and depression scale, quality of life, sleep status) will be taken. Third, each patient will receive the treatment of thumbtack needle for a total of 2 menstrual cycles. Last, the above baseline measurements will be taken again as soon as the treatment is finished and outcome measures will be recorded after the treatment.

Nct (2021). "Effect Of Treadmill Based Aerobic Exercise Intervention On Menstruation And Quality Of Life In Women With Polycystic Ovarian Syndrome." ClinicalTrails.gov.
	This study will be carried out on sixty females with polycystic ovarian syndrome (PCOS) patients will be randomly assigned into two equal groups: control group (30 women) will receive low caloric diet 1200 Cal/day) while study group (30 women) will receive the same diet regime and treadmill aeobic exercise

Nct (2021). "Effect of Visceral Manipulation on PCOS." ClinicalTrails.gov.
	This study was conducted to determine the effect of visceral manipulation on menstrual irregularities and hormonal profile in women with polycystic ovarian syndrome (PCOS). Thirty women having PCOS were chosen from the outpatient clinic of the faculty of physical therapy, Cairo University. They were randomly assigned into two groups equal in number. Group (A) (Control group), 15 PCOS women received a low caloric diet (1200 Kcal/day) for 3 months, while group (B) (Study group), 15 PCOS women received visceral manipulation to the pelvic organs and their related structures (8 sessions, once per week in the first month then once every other week for two months) in addition to the same low‐calorie diet as the group (A). Evaluations pre and post‐study for body weight, body mass index, female reproductive hormones [luteinizinghormone (LH), follicle‐stimulating hormone (FSH) and LH/FSH ratio] and menstruation‐related problems were done by weight‐ height scale, blood analysis, and menstruation‐specific domain of polycystic ovarian syndrome questionnaire (PCOSQ), respectively.

Nct (2021). "Effect of White Light on Fatigue Levels in Patients With Gynecological Cancer." ClinicalTrails.gov.
	White light therapy is one of the non‐pharmacological methods in the management of fatigue. Cancer‐related fatigue (CRF) is a persistent, subjective sense of physical, emotional, and/or cognitive tiredness or burnout. It is associated with cancer or cancer treatment from the first diagnosis until the end of life that is not proportional to recent physical activity. It was founded that 10,000 Lux bright white light administered in the morning hours reduced fatigue by 17% in patients with cancer and that the mean fatigue scores of patients decreased from 30.37 to 9.48 compared to before the light administration. According to NCCN (2020), white light of 10,000 Lux can be applied for 30‐90 minutes in the morning hours to regulate sleep and manage fatigue in the post treatment period as well as in cancer patients receiving active treatment. However, studies on this subject consist of small sample groups, and more studies are needed to identify the risks and benefits of the application and to determine the optimal application time and duration. The present study was aimed to evaluate the effect of white light on the fatigue levels of patients with gynecological cancer who were treated with chemotherapy. The patients with high levels of fatigue in every dimension were selected so as to have a homogeneous group. The research hypotheses were determined as follows: H0: White light has no effect on fatigue levels in patients with gynecological cancer. H1: White light reduces fatigue levels in patients with gynecological cancer.

Nct (2021). "The Effect of Yoga Practice on Pain Intensity, Menstruation Symptoms and Quality of Life in Primary Dysmenorrhea." ClinicalTrails.gov.
	In the study, 52 students will be randomly assigned to intervention (yoga) and control groups. The researcher will provide information about the purpose of the study and the study process by interviewing all the students in the sample online. All students participating in the study, who are in the yoga or control group of the study, will be given a data collection form as a pre‐test by the researcher. Hatha yoga will be applied to the students (n = 26) in the yoga group in the study. Considering the studies conducted with these students, it is planned to practice Hatha yoga for 60 minutes twice a week for three menstrual cycles (12 weeks). Yoga practice will be done online by the researcher Aslıhan Aksu (A.A.), who has a Yoga Alliance‐approved yoga instructor certificate, on the determined days and times using appropriate platforms. In the control group (n=26), no intervention will be made for 12 weeks. The results will be collected through data collection forms before the yoga practice and after the 12‐week yoga practice is completed. The data collection forms applied to all students in the yoga and control groups at the beginning of the study will be applied to the control group again at the end of 12 weeks. The primary expected result of the study is the effect of yoga on students' menstrual pain intensity. The secondary expected results of the study are to determine the effect of yoga on students' menstrual symptoms and quality of life.

Nct (2021). "Effect on Adaptation to Cancer of Mobile Application Developed for Gynecological Cancer Patients." ClinicalTrails.gov.
	This study was planned as a parallel, single‐blind, pre‐post‐test randomized controlled experimental study in which two groups (experiment‐control) will be compared. The block randomization method will be used. The patients who will participate in the research will be reached through social media networks related to cancer (Facebook and Instagram account of the Dance with Cancer Association, etc.) and the data will be collected from patients who are suitable for the sample characteristics through mobile application. The sample size was calculated in the G*power statistics program by utilizing the data of a study in which on cancer patients using a mobile application intervention was previously performed (α =0.05, d=0.75). Accordingly, it was found that 23 people should be taken for each group to sampling for 80% power. Considering that there might be losses, the number of samples was increased by 10% and it was planned to include a total of 52 people in the study. Intention‐to‐treat analysis will be performed to manage bias and losses. A pilot application will be conducted for 4 weeks with 6 patients regarding the usability of the mobile application and these patients will not be included in the study. At the end of 4 weeks, feedback will be received from the patients participating in the pilot application with the mobile application evaluation form. Necessary changes will be made in the mobile application in line with the feedback.

Nct (2021). "The Effectiveness of Anti-resistance Exercise on Lower Limb Lymphoedema Among Gynecological Cancer." ClinicalTrails.gov.
	Background: The incidence of lower limb lymphedema (LLL) after gynecological cancer surgery with lymphadenectomy is about 10‐46%. Lower limb lymphedema results in limited physical mobility and reduced patients' quality of life. A hospital ‐based complete decongestive therapy has been recommended to patients with LLL, including exercise, manual lymphatic drainage, compression therapy, and skin care. However, the inconvenience of the hospital‐based rehabilitation program limit the availability for those patients LLL. Home‐based exercise program may be feasible instead of the hospital‐based program. Few studies have evaluated the effectiveness of the home‐based lower extremity exercise on reliving LLL and improving quality of life in patients with LLL. Research Purposes: The main purpose of the study is to evaluate the effectiveness of a home‐based exercise program for relieving lower extremity lymphedema, including circumference measurement, bioimpedance spectroscopy (BIS), lower limb muscle strength, quality of life related to cancer & LLL, and fatigue. Methods: This study is a two‐ year project with a single‐blind randomized clinical trial. The participants are women with gynecological cancer surgery, aged of 20‐75 years and currently have lower extremity lymphedema. A sample of 76 participants will be stratified randomly assigned to an experimental group or a control group. The experimental group is to carry out a home‐based anti‐resistance exercise with elastic band other than a routine care of complex decongestive physiotherapy; while the control group is to carry out a routine care of complex decongestive physiotherapy. The home‐based program is a 12‐week exercise program. Data collections will be conducted before exercise (Baseline), during exercise (second months), and exercise program after completion. Measures includes (1) Physical examination: limb leg circumference measurement, bioimpedance spectroscopy (BIS), lower limb muscle strength, (2) Questionnaires: Functional status of lymphatic edema of LLL, fatigue, and EORTC‐QLQ‐C30. Anticipated Outcomes: Findings from this study could provide a reference of home‐based exercise guideline and be integrated into the care of activities for women following gynecological surgery with LLL.

Nct (2021). "Effectiveness of Dark Chocolate and Music in Dysmenorrhea." ClinicalTrails.gov.
	Primary Dysmenorrhea (PD) is defined as cramping pain in the lower abdomen, which occurs before or during menstruation without pelvic diseases. Contraceptive pills and non steroidal anti inflammatory drugs are commonly used in the treatment of PD. International (66.5% to 92.5%) and Turkey (87.7% to 80.1%) in the studies among university students show that a high percentage of dysmenorrhea. Dysmenorrhea negatively affects the school absenteeism of girls, their academic success and causes a lack of concentration. The rate of using pain medication due to dysmenorrhea is high among students. Music therapy has been shown to be effective in relaxing the mind and body, relieving anxiety, enhancing security, and increasing pain thresholds. Dark chocolate contains copper, which is used by the body to synthesize neurotransmitters called collagen and endorphins. Endorphin hormone is an analgesic and natural sedative to reduce pain intensity such as menstrual pain. This randomized clinical trial was designed to determine the effect of eating dark chocolate and listening music on PD, compared to a control group that no intervention in women of 18 years or older from the the Faculty of Health Sciences at the Manisa Celal Bayar University, Manisa, Turkey.

Nct (2021). "The Effectiveness of Parassacral Transcutaneous Stimulation Compared to Tibial Transcutaneous Stimulation, Home Protocol and Behavioral Therapy in the Treatment of Female Hyperative Bladder: randomized Clinical Trial." ClinicalTrails.gov.
	Introduction: The overactive bladder is a highly prevalent condition, which negatively impacts the quality of life and daily activities of women. Transcutaneous electrostimulation is currently a therapeutic alternative for urinary urgency symptoms. Although it can be applied to the sacral plexus or tibial nerve, the literature shows the effectiveness of these two modalities, in isolation, but there are few scientific studies that compare them as two therapeutic alternatives. Primary objective: to evaluate the efficacy between parascutaneous electrostimulation, tibial transcutaneous stimulation, and home protocol in the treatment of female overactive bladder. Methodology: This is a clinical trial, which will include women with a clinical complaint of overactive bladder, with or without urgency‐incontinence, who will be randomized into 3 groups: transcutaneous parasacral electrostimulation (EETP), transcutaneous tibial electrostimulation (EETT) and a third group, home transcutaneous parasacral electrostimulation (EETPD), will consist of women who have financial difficulties or locomotion to attend the clinic.All groups, in the first session, will be guided to conduct behavioral therapy and will receive an educational booklet with guidelines. The equipment to be used will have a wave frequency of 10 Hz, a pulse width of 700 µs and a 20‐minute session, with intensities according to the participant's tolerance. The intervention protocol of the EETP group is 30 sessions, three times a week, with an active electrode in the parasacral region. For EETT, 30 sessions will also be held, three times a week, with the electrode active in the tibial region. Participants will be captured at educational events held by the Pelvic Floor Service Center in Salvador and the metropolitan region. Participants will answer the basic anamnesis questionnaires, ICIQ‐OAB, ROMA III criteria, Bristol scale, Hospital Anxiety and Depression Scale, Oswestry scale, Pittsburgh sleep quality index and Female Sexual Function Index. Then, the assessment of the bladder neck and the thickness of the bladder wall will be performed by 2D ultrasonography via suprapubic and intravaginal, following the assessment protocol described for the intervention groups. Primary outcomes: clinical improvement of symptoms, urinary frequency, episodes of urgent urinary incontinence, presence of adverse effects and constipation. Secondary outcomes: quality of life, sexual function, quality of sleep, anxiety and depression, muscle function (PERFECT and electromyography), lumbar‐pelvic pain (pain intensity) and ultrasound. Participants will be followed for a minimum of 12 months to verify the long‐term response, returning every 3 months. Expected results: The outpatient transcutaneous parasacral electrostimulation is expected to be superior when compared to the tibial transcutaneous electrostimulation in the resolution of the symptoms of the overactive female bladder.

Nct (2021). "The Effectiveness of Relaxation Training on Primary Dysmenoreh and Menstrual Symptoms." ClinicalTrails.gov.
	Dysmenorrhea is a common gynecological complaint in women of reproductive age, characterized by lower abdominal pain that occurs a few hours before or with the onset of menstruation and persists for 1‐2 days. It is more common in adolescent and young women. It is divided into primary and secondary dysmenorrhea. The prevalence of primary dysmenorrhea varies between 17‐95%. Primary dysmenorrhea, unlike secondary dysmenorrhea, is due to contraction of the myometrium without pelvic pathology. Pain occurs with every menstrual cycle. Generally, cramp‐like pain in the suprapubic region may be accompanied by nausea, vomiting, headache, dizziness, sweating, diarrhea, insomnia and syncope . While primary dysmenorrhea is more common in nulliparous, both its severity and incidence decrease with increasing age and parity. Primary dysmenorrhea is pelvic pain that is caused by the natural production of prostaglandins and is not associated with pelvic pathology, and is among the common causes of admission to emergency services. In the pathogenesis of primary dysmenorrhea, it is thought to be associated with prostaglandin production, which increases with vasoconstriction of the uterine blood vessels, leading to uterine contractility and ischemia. Primary dysmenorrhea does not threaten the life of women, but it can affect the quality of life negatively and prevent work and school continuity. There are various relaxation techniques in the literature to reduce the pain and improve the quality of life of women with primary dysmenorrhea. Relaxation techniques are effective and easy‐to‐apply self‐management therapy in reducing the effects of pain, stress, depression, anxiety and mood changes on the individual and in controlling the body. Laura Mitchell's Simple Physiological Relaxation Training is a standard method with the advantages of requiring less concentration, being learned in a short time and showing a rapid effect, and is widely used especially in the field of obstetrics and gynecology. It is known that this technique, which includes diaphragmatic breathing, improves immune system functions and quality of life, and also reduces depression. The aim of this study is to evaluate the effectiveness of Laura Mitchell's relaxation training on primary dysmenorrhea and menstrual symptoms. METHOD The study will be carried out on women who have been diagnosed with primary dysmenorrhea, have a regular menstrual cycle (28±7 days), have menstrual pain higher than 4 cm according to the visual analog scale (VAS), and wish to voluntarily participate in the study. The questionnaire created by the researchers will be administered online. Before starting the study, the consent of the participants will be obtained via online link. The women included in the study will be divided into 2 groups as experimental and control groups by applying randomization using the random drawing method. Data collection Evaluations were evaluated according to the physical (age, height, body weight, body mass index) and demographic data of the individuals (age at menarche, mean cycle duration, duration of menstruation, pain status, duration of pain, number of pads used on the busiest day, presence of menstrual symptoms experienced during menstruation period). intensity) will be recorded. Individuals will be examined for 5 menstrual cycle follow‐ups, 4 of which are consecutive. Pain intensity of individuals will be evaluated with Visual Analog Scale (VAS) and menstrual symptoms will be evaluated with Menstrual Symptom Scale (MSS). To the individuals participating in our study; The 1st day of the 1st menstruation is the 1st evaluation, and the data will be collected with VAS and MSS for both groups, and relaxation training will begin for the experimental group. The 1st day of the 2nd menstruation is the 2nd evaluation, and the data will be collected with VAS and MSS for both groups, and relaxation training will be continued for the experimental group. The 1st day of the 3rd menstruation will be the 3rd evaluation. Data will be collected with VAS and MSS for oth groups, and relaxation training will be continued for the experimental group. The 1st day of the 4th menstruation will be the 4th evaluation, and the data will be collected with VAS and MSS for both groups, and the relaxation training will be terminated for the experimental group. They will be free to continue exercising until the seventh menstruation. 1st day of 7th menstruation

Nct (2021). "Effectiveness of 'Supportive Parenting App' on Parental and Newborn Outcomes." ClinicalTrails.gov.
	The Supportive Parenting App is a theory‐based perinatal educational intervention for couples administered through a mobile application. The intervention comprise of knowledge‐based content, informational videos and audio, discussion forum, peer volunteer chat group, and a frequently asked questions (FAQ) expert advice section. The aims of the study are to: 1. develop theory‐based supportive parenting App (SPA) intervention for both first‐time and experienced parents across perinatal period 2. examine its effectiveness on parental outcomes: including maternal depression at 12 months postpartum (primary outcome), paternal depression, parental anxiety, parenting self‐efficacy, help ‐ seeking behavior (social support), parental bonding and parenting satisfaction (secondary outcomes); and new‐born outcomes: physical, social and emotional developments (secondary outcomes) 3. evaluate SPA's cost‐effectiveness as compared to standard perinatal care across major restructured hospitals, and 4. examine the perceptions of parents in receiving this intervention. When compared with those in the control group receiving standard care: 1. parents receiving SPA intervention will have better‐ emotional well‐being (reduced depression and anxiety);parenting self‐efficacy; social support; bonding and satisfaction. 2. new‐borns of parents receiving SPA will have better physical, social and emotional development 3. It will be more cost‐effective to provide SPA than the standard care

Nct (2021). "Effects Of Combined Cryolipolysis And High Intensity Interval Training On Insulin Resistance And Body Composition In Polycystic Ovarian Patients." ClinicalTrails.gov.
	This study will be carried out on ninety females with polycystic ovarian syndrome (PCOS)l. Their age ranges from 17‐28 years, body mass index 25‐30 Kg/m2. They experience hyperandrogenism and hyperinsulinemia. PCOS females will be randomly assigned into three equal groups: group (A) consists of 30 women who receive cryolipolysis and group (B) consists of 30 women who receive high intensity interval training and group (C) receive both

Nct (2021). "Effects of Dietary and Weight Management on Pregnancy Outcomes in Mobile Medical Platform." ClinicalTrails.gov.
	This is a cluster intervention study. A randomized controlled trial in pregnant women will be initiated at 8‐12 weeks of gestation util delivery. Pregnant women who received routine antenatal examination in Beijing Obstetrics and Gynecology Hospital will be divided into two groups . One group contained 1000 cases as the control group , and the other group contained 1000 cases as a whole . The intervention contents included health education , nutritional analysis and individualized dietary guidance combined with mobile medical treatment and face‐to‐face teaching during the early , middle and late pregnancy stages. The primary outcome will be the incidence of GDM and the secondary outcome will be the incidence of hypertensive disorders of pregnancy , cesarean section , premature delivery , macrosomia, large for gestational age and so on.

Nct (2021). "Effects of External Neuromuscular Electrical Stimulation in Women With Urgency Urinary Incontinence." ClinicalTrails.gov.
	Our study will be carried out with female patients between the ages of 18‐65 who have Urge urinary Incontinence (UUI) symptoms and applied to the Recep Tayyip Erdogan University Training and Research Hospital, Gynecology and Obstetrics Policlinic. Inclusion criterias are; who do not want to use medication, who do not benefit from medication for a long time or who do not use any medication. Exclusion criterias are; Those with any malignant conditions, those with neurological disease, those with infection, pregnant women, those with pelvic organ prolapse above stage 2 according to the POP‐Q staging, those with cardiac implants and pacemakers, those with cardiac arrhythmia, those with urinary retention, those with sensory loss, copper coil intrauterine those who wear a vehicle, patients with metal implants and patients with communication and cooperation problems. Before starting the study, all participants will be questioned about demographic and physical characteristics, medical, obstetric, gynecological and urological history and drug use. After these evaluations, sensory and reflex evaluations will be made. Sensory assessment will be performed with a light touch test to the hip circumference and pelvic floor muscles. In reflex evaluation, anal and bulbocavernous reflexes will be checked. All of the applications will be carried out by Specialist Physiotherapist Tuğba Birben under the supervision of Specialist Gynecologist Physician Beril Gürlek. Our study will be in 2 groups. It is estimated that the number of people will consist of 40 volunteers, with 20 patients for each group. The sample size will be determined after the pilot study. Patients who were diagnosed with UUI, met the study criteria and accepted to be included in the study, within a period of 9 months after the approval of the ethics committee, with the four‐block randomization method, via the website https://www.sealedenvelope.com/simple‐randomiser/v1/lists will be included in groups according to randomization. lifestyle suggestions (LSS)+ NMES (NMES group) will be applied to the first group and LSS + SHAM Electrical Stimulation (SHAM ES group) will be applied to the second group. Each group will be included in the 8‐week treatment program for 30 minutes 3 days a week. Pelvic floor muscle function of all participants will be evaluated with the Modified Oxford Scale before treatment, at the end of the 4th week and after treatment. In addition, women's bladder function with the urinary diary, incontinence symptoms with the International Incontinence Consultation Questionnaire‐Short Form (ICIQ‐SF) and the Coital Incontinence Score (CIS), quality of life with the King Health Questionnaire (KHQ) and Sexual Function will be evaluated with Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ‐12). At the end of the 8th week, both the Subjective perception of improvement and treatment satisfaction of the patients will be questioned.

Nct (2021). "Effects of Fasting Mimicking Diet (FMD) in Women With Polycystic Ovary Syndrome (PCOS)." ClinicalTrails.gov.
	Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive‐aged women, affecting 6‐21% (depending on the applied diagnostic criteria) of this population worldwide. PCOS is characterized by hyperandrogenism and/or chronic anovulation which can manifest with a range of symptoms (e.g., hirsutism, acne, oligomenorrhea, and infertility) and is associated with increased risk of cardiometabolic diseases, including hypertension, dyslipidemia, insulin resistance (IR), and type 2 diabetes mellitus (T2DM). Moreover, PCOS is linked to increased psychological morbidity (e.g., increased risk of stress, depression, low self‐esteem, poor body image, and reduced health‐related quality of life). The exact PCOS etiology is unknown, but increased adiposity is considered pivotal. Indeed, almost 90% of women with PCOS are overweight or obese, and even moderate weight loss (e.g., 5%) may result in clinically meaningful improvements in hyperandrogenism and menstrual regularity. Also, women with PCOS often have more severe IR than weight‐matched women without PCOS, whilst their increased susceptibility to obesity may further exacerbate IR and the accompanying metabolic and reproductive dysfunctions. As such, women with PCOS exhibit an increased risk of impaired glucose tolerance and T2DM regardless of weight and age. Management of overweight/obese women with PCOS focuses on weight loss through regular exercise and diet, aiming to alleviate its clinical manifestations and lower the related risk of T2DM and cardiovascular disease. Fasting‐induced negative energy also potently affects the hormones such as estradiol, testosterone, and leptin; and complex interactions exist between metabolic signals and ovarian steroids. However, fasting is difficult to implement. It is of great interest to develop feasible and efficacious fasting‐mimicking diets (FMD) to alleviate the burden of fasting while preserving the beneficial effects of fasting. In a case study, a 23‐year‐old female diagnosed with PCOS had her persistent cystic acne resolved after just 3 cycles of self‐administered fasting‐mimicking dieting. In addition, FDM induces a reduction in insulin levels, fasting glucose, BMI, decreased adiposity, and inflammation rates. The investigators hypothesize that a specially designed FMD will induce physiological changes similar to prolonged fasting and will decrease risk factors associated with metabolic syndrome and alleviate symptoms of PCOS. The purpose of the study is to evaluate the effect of FMD in women with PCOS. Regarding the study model, a crossover will be applied. Our crossover design is the simplest model known as 2 x 2 where two treatments are compared in two‐period, two‐sequence model. Each washout, between consecutive periods, is done so that the previous treatment does not affect the response to the next treatment. The main advantage of a crossover design over the parallel group is the opportunity it offers to compare the effects of treatments within‐subjects, which is not possible with a conventional parallel‐group design. Additionally, a crossover design usually requires a smaller sample size to reliably estimate the magnitude of the treatment effect. That is, any component of an individual's response that is consistent over time is removed from the treatment comparison. Study participants will be randomized and assigned to arm 1 (n° = 50, control patients) or arm 2 (n° = 50, patients undergoing FMD). Patients in the FMD group will be asked to consume FMD, which will be provided with a box, for 5 continuous days, and to return to their normal diet after completion until the next cycle which will start 25 days later, for a total of three months. The two groups will then be exchanged in the third month so that the control group will also be subjected to FMD in the following three months. The main parameters that will be texted, are all major symptoms associated with PCOS, including menstrual cycle regularity, ovarian morphology (by ultrasound); hirsutism (by the Ferriman‐Gallw (FG) scoring method), and acne score. Moreover, improvement in metabolic, inflammatory, and psychological markers will be also evaluated. Both control and FMD patients will complete anthropometric measurements every month (at the end of each FMD cycle). After three months, patients will be crossed for another 3 months: patients with arm 1 control will be instructed to follow FMD, while patients with arm 2 undergoing FMD will be asked to continue their normal diet. Follow‐up exams will be conducted for both groups at the end of the 6th month. Thereafter, all patients will be asked to continue their normal diet for another three months and will undergo further follow‐up at the end of the ninth month. Blood chemistry analyzes will be performed at time zero, at 3 and 6 months, while gynecological and nutritional checks will be performed at time zero at 3 to 6 months and at the end of the study (t = 9 months). The total duration of the study is 9 months. The evaluation of the menstrual history and the anthropometric parameters will be measured during the gynecological and nutritional checks. The psychological/psychiatric evaluation will be carried out at T0, at 3 to 6 months, and at 9 months. Blood samples will also be used for IGF‐1 analyzes (IFOM, Milan). Both control and FMD patients will fill out a food diary. Patients undergoing FMD will be contacted by phone for nutritional assistance once a day during the 5 days of FMD. Additionally, to assess adherence to the 5‐day nutritional plan for FMD, patients will independently assess their ketonuria with appropriate sticks. Every month, all enrolled patients will note the possible date of menstruation and the duration of the cycle.

Nct (2021). "Effects of Fasting on Success Rates of Assisted Reproductive Techologies." ClinicalTrails.gov.
	This 2‐arm, randomized, controlled exploratory clinical trial aims to explore fasting as a novel supportive treatment in female infertility during IVF / ICSI. The participants will be randomized in two groups: a fasting group and a waiting list. The intervention group follows a fasting intervention, whereas the patients on the waiting list continue their normal diet. All groups will be trained and accompanied by medical experts. In addition, qualitative interviews will be conducted including individual and focus group interviews with a subgroup of participants.

Nct (2021). "Effects of High-Intensity Interval Training and Strength Training On Levels of Testosterone and Physical Activity Among Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	High intensity interval training will be performed over the course of 12 weeks and will be compared with the group performing strength training. Baseline assessments will be done before the start of the first session and post‐test assessment will be done after the last session of the study. Envelope method is used for the purpose of randomization. 50 envelopes having a title of group A and group B will be made and divided into two (25 in each group). Mutually exclusive technique will be used and the envelope once picked will not be replaced within the groups. Sample size is calculated by using a previous study conducted in 2015 titled as, 'Effects of High Intensity Interval Training and Strength Training on Metabolic, Cardiovascular and Hormonal Outcomes in Women with Poly cystic Ovary Syndrome: A Pilot Study' by taking a confidence interval CI of 95%, power of test 80%, standard deviation of 6.3 and mean difference of 5.2, a sample size of 50 is calculated. For the analysis of the data MedCalc software version 19.0.5. will be used. Descriptive statistics will be performed for the purpose of demographic information and this data will be presented in terms of frequency and percentage. Skewness and Kurtosis will be used in order to determine the normality of data. If the data is normally distributed, then for within the group analysis dependent T test will be performed. However, in case the data is not normally distributed Wilcoxon Sign Rank test will be performed. Independent T test will be performed for the comparison between the two groups.

Nct (2021). "Effects of Myo-inositol in Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	The study will involve 60 women in the reproductive period, with a variable between 18 and 36 years old and diagnosed with polycystic ovary syndrome (PCOS), according to Rotterdam‐ European Society of Human Reproduction and Embryology (ESHRE) / American Society for Reproductive Medicine (ASRM) criteria defined in 2003 and by the entity The Androgen Excess and Polycystic Ovary Syndrome Society (AE‐PCOS) 2018, and insulin resistance (presence acanthosis nigricans) or glucose intolerance (fasting glycemia, glycated hemoglobin or 75g glycemic overload and blood glucose assessment after 2 hours). It is a comparative and non‐inferiority study of myo‐inositol in relation to metformin. They will be divided into two groups of 30 patients: Group I (control) ‐ they will receive metformin, orally, three times a day; Group II (experiment) ‐ they will receive myo‐inositol 2g, orally, twice a day.

Nct (2021). "The Effects of Pelvic Floor Muscle Training in Women With Overactive Bladdder." ClinicalTrails.gov.
	Overactive bladder (OAB) is defined by the International Continence Association as an "urgency with or without urge urinary incontinence, often accompanied by frequency and nocturia." Accordingly, pelvic floor muscle training (PFMT) plays an important role in the management of OAB. However, a recent systematic review suggests that PFMT is insufficient against OAB.

Nct (2021). "Effects of Postpartum Nurse Navigation Program." ClinicalTrails.gov.
	Primiparous pregnant women who come to the pregnancy outpatient clinic, are at 36 weeks of gestation or more, meet the inclusion criteria and volunteer, will be informed about the program and will be included in the sample of the study. There will be two groups assigned by the stratified block randomization method in the study. The number of samples to be taken into the control and intervention groups was determined by power analysis and the sample size was planned to be 32 mothers for the intervention group and 32 mothers for the control group. In addition to routine hospital care, the intervention group will receive navigation program‐based nursing care that includes three home visits, three phone calls, and sending text messages at five different times. The control group will not receive any intervention other than routine hospital care practices. The data of the research; "Data Collection Form on Descriptive Characteristics", "Postpartum Mother and Newborn Evaluation and Diagnosis Form", "Mother and Newborn Problems Evaluation Form in the Postpartum Period", "Mother and Baby Follow‐up Evaluation Form in the Postpartum Period", "Self‐Care Power" Scale', 'Postpartum Quality of Life Scale', 'Postpartum Specific Anxiety Scale', 'Edinburgh Postpartum Depression Scale' and 'Physical Symptom Severity Scale' will be collected using descriptive statistics (number, min., mean, standard deviation, standard deviation) in the evaluation of the data. max.) will be used. The conformity of the data to the normal distribution will be evaluated with the Shapiro Wilks test. The relationship between them in qualitative variables will be evaluated with the chi‐square test and Fisher's exact test. The Cochran Q test will be used to examine change over time. In numerical variables, according to the normal distribution; In independent groups, t test, Mann Whitney U test, one‐way analysis of variance (ANOVA), Kruskal Wallis Analysis will be used. Before and after repeated measurements, according to the normal distribution; In repeated measurements, one‐way analysis of variance or Friedman test will be used. Significance will be evaluated at the p<0.05 level. The independent variables of the research will be stated as numbers and percentages.

Nct (2021). "Efficacy and Safety of Fuke Qianjin Capsule in Patients With Pelvic Inflammatory Diseases." ClinicalTrails.gov.
	Study participants will be randomly assigned to Test or Control group and the following schedule will be followed Test group: metronidazole tablets + doxycycline hyclate tablets simulant are consecutively taken for 14 days, while Fuke Qianjin capsule is consecutively taken for 28 days. Control group: metronidazole tablets + doxycycline hyclate tablets, are consecutively taken for 14 days, while Fuke Qianjin capsule simulation is consecutively taken for 28 days. Fuke Qianjin Capsules and their simulants are taken as 2 capsules at a time, 3 times a day, orally after breakfast, lunch and dinner, respectively; Metronidazole Tablets are taken as 2 tablets (0.2 g/tablet) at a time, twice a day, at the same time as breakfast and dinner, respectively; Doxycycline Hyclate Tablet and their simulants are taken as 1 tablet (0.1 g/tablet, Doxycycline Hyclate Tablet calculated as C22H24N2O8) at a time, twice a day, at the same time as breakfast and dinner, respectively. Scoring pain, symptoms, local signs, routine leucorrhea, cervical secretions, gynaecological B‐ultrasound will be examined before the enrollment and after study completion.

Nct (2021). "Efficacy and Safety of PEG-rhG-CSF in the Prevention of Neutropenia After Chemo in Pts With Gynecological Malignancies." ClinicalTrails.gov.
	This study is a multi‐center, forward‐looking, open, randomized, controlled clinical trial. This study aims to analyze the effects of Mecapegfilgrastim Injection prevention versus non‐prevention for neutropenia in ovarian cancer, cervical cancer, endometrial cancer patients after chemical therapy. Patients are randomized into study group and control group. All patients receive PTX+platinum chemotherapy of 3 weeks. In study group, patients accept PEG‐rhG‐CSF 24‐48 hours from the chemotherapy. While the control group patients are only observed closely. Patient receive three courses of treatment. The primary end is the incidence of 3/4 level neutropenia in three courses of chemotherapy. The secondary ends include: the incidences and duration of neutropenia in every course of chemotherapy, the incidences of FN in three courses and every course of chemotherapy, the incidences of infection in three courses and every course of chemotherapy, the delay time of the next cycle of chemotherapy due to FN or infection, the RDI of the second and third cycles of chemotherapy, adverse events related to G‐CSF, quality of life, cost of medicine and admitting.

Nct (2021). "Efficacy and Safety of SG001 Combined With PLD in Patients With Platinum-resistant Relapsed EOC." ClinicalTrails.gov.
	This is a multicenter, randomized, controlled, open‐label, phase II clinical study to evaluate the efficacy and safety of SG001 in combination with doxorubicin hydrochloride liposome injection in patients with platinum‐resistant relapsed intermediate to advanced epithelial ovarian cancer, and to provide a basis for recommending the SG001 combination dosing regimen for subsequent studies. This study will enroll patients with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, FIGO stage II‐IV, platinum‐resistant relapse (defined as disease progression within 6 months after the last platinum‐containing chemotherapy) and non‐platinum refractory (defined as disease progression within 4 weeks after the first platinum‐containing chemotherapy) with up to three prior lines of platinum‐containing systemic chemotherapy, up to two lines of platinum‐free systemic chemotherapy, and at least one measurable tumor lesion (according to RECIST 1.1).

Nct (2021). "Efficacy of Empagliflozin or Linagliptin as an Alternative to Metformin for Treatment of Polycystic Ovary Syndrome." ClinicalTrails.gov.
	Patients with polycystic ovary syndrome will be randomized to three arms: ‐ Metformin (standard care) ‐ Empagliflozin or Linagliptin Resolution of the syndrome in addition to normalization of sex hormones, metabolic and inflammatory parameters will be tested

Nct (2021). "Efficacy of Injectable Fentanyl in Sublingual Route Versus Oral Morphine Syrup for Breakthrough Pain." ClinicalTrails.gov.
	objective; To comparison the efficacy of injectable fentanyl in sublingual route versus oral morphine syrup for breakthrough pain in gynecologic cancer patients with chronic cancer pain Population : gynecologic cancer patients with chronic cancer pain that use opioid drug for basal pain and had experienced of breakthrough pain cancer in Rajavithi hospital sample size : 20 person/group Method ; Randomized control trial , Prospective Intervention : group A : injectable fentanyl in sublingual , group B : oral morphine syrup Primary outcome : to measure pain score after drug is given at 5, 15, 30, 45, 60 and 120 min secondary outcome : to record side effect of drug is given at 5, 15, 30, 45, 60 and 120 min Statistical method ‐ Categorical data = Chi‐square test or Fishers' exact test ‐ Continuous data : comparison with Student t‐test in normal deviation data and Man‐Whitney U‐ test in abnormal deviation data • Analytical data with Pearson's correlation, Linear regression or Binary Logistic regression, Repeated Measures ANOVA with OR (95%CI) and p‐value <0.05

Nct (2021). "Efficacy of Internet-based Cognitive Behavioral Therapy for Endometriosis." ClinicalTrails.gov.
	Endometriosis is a chronic disease in which endometrium‐like (uterine lining‐like) cells settle outside the uterus in the abdomen (Dunselman et al., 2014). The Endometriose Vereinigung Deutschland reports that between eight and 15 percent of all women during reproductive age are affected and that there are 40,000 new cases annually in Germany (Endometriose Vereinigung Deutschland e.V., 2020). Thus, endometriosis is the second most common gynecological disease. Despite the high prevalence, the etiology and pathogenesis of many factors remains unclear. Misdiagnoses are common and to reach the correct diagnosis it takes an average of 5 to 8.9 years (Chaman‐Ara, Bahrami & Bahrami, 2017). So far there is no curative treatment option and the primarily medical treatment options are sometimes associated with serious side effects (Moradi, Parker, Sneddon, Lopez & Ellwood, 2014). Endometriosis is characterized by a multitude of physical as well as considerable psychological symptoms that significantly reduce the quality of life of those affected (Gao et al., 2006). For example, endometriosis is associated with higher levels of depression and anxiety disorders (Pope, Sharma, Sharma & Mazmanian, 2015). A psychotherapeutic supplement to the primary medical treatment to promote disease coping and expansion of coping strategies therefore appears sensible. In the planned study, a CBT program specifically for endometriosis sufferers will therefore be developed and evaluated. Previous intervention studies aimed at improving the quality of life of endometriosis sufferers examined mind‐body interventions such as yoga (Gonçalves, Barros & Bahamondes, 2017), relaxation training (Zhao et al., 2012) and acupuncture in combination with conversational psychotherapy (Meissner et al., 2016). Hansen et al. (2017) were able to show in an uncontrolled pilot study (N = 10) that mindfulness‐based psychotherapy significantly reduces the burden of endometriosis. Overall, the number of psychological intervention studies on endometriosis is very low and their quality often requires a critical classification due to methodological limitations (for an overview see Evans, Fernandez, Olive, Payne & Mikocka‐Walus, 2019; Van Niekerk, Weaver‐Pirie & Matthewson, 2019). Numerous evidence of effectiveness from the area of chronic pain disorders (Williams, Fisher, Hearn & Eccleston, 2020) as well as disorders in the area of women's health such as premenstrual dysphoric disorder (PMDD, Weise et al., 2019) undermine a possible effectiveness of CBT in endometriosis. To the best of our knowledge, however, there is no study to date that has tested the effectiveness of CBT for improving the quality of life of endometriosis sufferers. The treatment program developed as part of the planned study is to be implemented as an internet‐based intervention. A large number of studies confirm the effectiveness of internet‐based CBT (iCBT) in various mental (Loughnan, Joubert, Grierson, Andrews & Newby, 2019), psychosomatic (Andersson, Cuijpers, Carlbring, Riper & Hedman, 2014) and somatopsychic diseases (Bernardy, Füber, Köllner & Häuser, 2010). The iCBT has now established itself as being as effective as face‐to‐face therapy (Carlbring, Andersson, Cuijpers, Riper & Hedman‐Lagerlöf, 2018; Andersson, Carlbring & Rozental, 2019) The internet‐based implementation in the present study has various advantages: On the one hand, the effectiveness of the iCBT can be checked efficiently and in a resource‐saving manner (Hedman, Andersson, Ljoeétsson, Axelsson & Lekander, 2016). On the other hand, endometriosis sufferers can be addressed throughout the German‐speaking area, which ensures that a sufficient sample size can be achieved. Ultimately, those affected that would otherwise not receive any treatment due to the lack of regional availability of interventions, also have access to treatment. In addition, issues such as the desire to have children and endometriosis often lead to shame. An intervention offered online and anonymously can encourage the use f assistance here. The aim of the study is to examine the effectiveness of iCBT in reducing the stress and impairment caused by endometriosis and in increasing the health‐related quality of life.

Nct (2021). "Efficacy of Letrozole Versus Clomiphene Citrate on Ovulation Induction in Patients With Polycystic Ovarian Syndrome." ClinicalTrails.gov.
	Discrepancy between ovulation induction rate and pregnancy rate is related to anti‐estrogenic effects on cervical mucus and endometrium and long acting gonadotrophins are more effective than clomiphene citrate. This study was aimed at comparing frequency of induction of ovulation in women with polycystic ovarian syndrome treated with Letrozole versus clomiphene citrate.

Nct (2021). "Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer." ClinicalTrails.gov.
	The trial includes two arms, one of which is experimental arm with MP regimen chemotherapy that is compared with other arm with the standard TC regimen chemotherapy. To participate in this study, patients must have histologically confirmed epithelial ovarian carcinoma (ОС) or fallopian tubes carcinoma and FIGO stage IIB, IIC, III, or IV disease and BRCA1/BRCA2 germline mutation. All OC patients before the treatment start are subjected to the testing for BRCA1/BRCA2 mutations cases that are examined by the next‐generation sequencing. All BRCA1/2 mutation carriers, who could not be treated by primary debulking surgery owing to extensive tumor spread, are given neoadjuvant chemotherapy. OC patients are randomly assigned to receive the TP regimen (paclitaxel at175 mg/m2 and carboplatin AUC5‐6) or the MP regimen (mitomycin C at 10 mg/m2 and cisplatin at 100 mg/m2). After 3‐4 cycles of neoadjuvant chemotherapy, a formal assessment is made and patients are categorized according to the RECIST 1.1 standard. The patients who show partial clinical response or complete clinical response has to be undergoing interval debulking surgery. The patients who show stabilization of the process should continue chemotherapy for up to 6 cycles, followed by an assessment of the treatment (it is possible to continue up to 12 cycles) and a decision on whether to perform interval debulking surgery. Patients categorized as progressed clinically has to finish the protocol treatment and are allowed to receive any secondary treatment at the investigators' discretion. For those patients undergoing interval debulking surgery has to receive further regimens (up to 6 cycles of protocol treatment) without changing chemotherapy regimen. After six cycles of protocol treatment, the patients had to be categorized with regard to their final response status with the use of clinical/radiologic assessment. Patients not showing disease progression at this point could cease all cytotoxic therapy or can receive three additional cycles of protocol treatment. While on protocol therapy, patients underwent the following procedures: symptom recording and physical examination every 3 weeks, complete blood cell counts weekly for the first two cycles and every 3 weeks thereafter, and laboratory tests of blood and CA 125 measurements on day 1 of each cycle. Radiologic investigations to document the status of all measurable lesions noted at baseline had to be repeated after three, six, and nine cycles of chemotherapy. Once patients were off the protocol therapy, they were monitored for assessment of disease status every 3 months for 2 years and every 6 months thereafter. Monitoring comprised clinical examination and CA 125 estimation; routine computed tomography scans were not required but were requested if the CA 125 level rose and/or symptoms developed.

Nct (2021). "Efficacy of Surface Electrical Stimulation for Urge Urinary Incontinence in Women." ClinicalTrails.gov.
	The purpose of this research is to evaluate the effectiveness of the ELITONE‐UUI electrical muscle stimulation device on treating urge incontinence in women. The aim of the device is to stimulate the pelvic floor muscles and surrounding structures to improve urinary incontinence. This is a randomized prospective controlled study of two active groups with a stimulation frequency difference between the groups.

Nct (2021). "Efficacy of Using a Closing Pack to Reduce Postpartum Sepsis." ClinicalTrails.gov.
	Pregnant patients meeting the inclusion criteria undergoing elective or emergency caesarean section will be eligible for recruitment. Patients will be randomised into two arms. In the control arm sheath and skin closure will be performed with the instruments used to perform the caesarean section, as per the current standard of care. In the intervention arm, after suturing the uterine incision and obtaining hemostasis and before commencing closure of the sheath and skin, the surgical team (obstetrician, assistant and scrub sister) will don clean sterile gloves, open clean sterile linen to drape on top of the existing linen and open a pack of clean sterile instruments to close the sheath and skin.

Nct (2021). "Electrical Stimulation in Women With Pelvic Organ Prolapse." ClinicalTrails.gov.
	This study is planned as a prospective, sham radomized controlled study. Individuals who volunteered to participate in the study, complying with the inclusion criteria and signed the consent paper will be randomly allocated into ES and Sham ES groups. The study includes women aged 18‐65 diagnosed with staged 1‐2 POP by the physician.All patients were evaluated by the same doctor who performed the POP‐Q measurement, who was blinded to the baseline results. The treatment of patients will be given by the same therapist. Measurements will be made 3 times at baseline (before treatment), interim period (4th week) and after treatment.

Nct (2021). "Electroacupuncture Treatment for Urinary Incontinence (UI) in Women." ClinicalTrails.gov.
	The International Continence Society defines urinary incontinence (UI) as the objectively demonstrable involuntary loss of urine. It affects women of any age. UI significantly impairs patients quality of life, limits their autonomy and reduces their self‐esteem. The impairment of health‐related quality of life due to UI can be even greater than that caused by some chronic diseases such as diabetes or high blood pressure. It is common for this type of disorder to be significantly associated with depressive symptoms and feelings of anxiety, which end up affecting the physical, psychological, social, cultural and sexual levels. UI is classified into: Stress or Effort UI (the most frequent), urge UI and mixed UI. In stress UI, involuntary urine leakage is associated with physical exertion that causes an increase in abdominal pressure; it occurs as a result of a failure in the urethral resistance mechanisms. In urge UI, the involuntary loss of urine is preceded by a compelling desire to urinate; it is due to an increase in urinary bladder contractility. In mixed UI, involuntary urine loss is associated with stress and urge incontinence. The prevalence of UI varies according to the type of study, the definition and assessment of UI and the characteristics of the population studied (mainly age and sex, with the frequency increasing with age and in women). Worldwide, figures ranging from 5% to 72% have been published; in Spain, the available data range from 15% to 42%, the average prevalence being estimated at 40.6%. The therapeutic approach to UI can be pharmacological (anticholinergics, alpha‐blockers and topical estrogens are the most commonly used agents), urological surgery, external devices (such as pessary and urethral occluder), pelvic floor exercises and stimulation by electroacupuncture. The International Consultation on Urological Diseases recommended pelvic floor muscle training as A level evidence treating simple mild and moderate stress urinary incontinence, which curative rate varies 30% to 60%, although it is a lifelong treatment. Conservative interventions such as pelvic floor muscle training are more likely to be used than drugs or surgery while a woman is pregnant or in the postnatal period. Pelvic floor exercises for the treatment of urinary incontinence was popularized by Arnold Kegel (1948). It has been recommended in the treatment of stress and mixed urinary incontinence, but has increasingly become part of the treatment of urge UI. It is based on two functions of the pelvic floor muscles: support of the pelvic organs, and a contribution to the urethral sphincter closure mechanism. From the interpretation of traditional Chinese medicine, the problem of urinary incontinence may be due to a deficiency of energy or "Qi". The pelvic floor, bladder and anal sphincter need significant energy to function properly. This is why it is thought that acupuncture may be a beneficial treatment, as it may increase energy along the urinary tract. UI can be included in two syndromes depending on the signs and symptoms presented by the patient. Our investigators work compares the effectiveness of electroacupuncture on the point R7 together with pelvic floor exercises versus pelvic floor exercises alone.

Nct (2021). "eMBC for Perinatal Depression and Anxiety." ClinicalTrails.gov.
	A parallel group randomized controlled trial (RCT) will be conducted. Eligible and consenting patients with depression and/or anxiety will be randomized in a 1:1 ratio to either the eMBC condition or a control condition. The study will be stratified by diagnosis (major depressive disorder vs generalized anxiety disorder). 80 patient participants will be recruited from the Reproductive Life Stages (RLS) Program at Women's College Hospital. The active treatment phase of the study is 12 weeks. Outcomes will be measured online and by phone at 4‐, 8‐, and 12‐ weeks post‐randomization. Following the completion of the study, some participants will be asked to participate in follow‐up interviews. RLS psychiatrists whose patients participated in the study will participate in a focus group.

Nct (2021). "Endocare for Pelvic-perineal Pain Related to Endometriosis Used at Home." ClinicalTrails.gov.
	Women with endometriosis experience recurrent pelvic‐perineal pain impairing the quality of life, among other things. Endometriosis‐related pain negatively impacts the sexual, family and work life. Apart from the usual painkillers, the doctor's current therapeutic arsenal is limited to hormonal contraceptives and surgery. As endometriosis‐related treatments do not currently address all of the patients' problems, developing a new, effective, non‐pharmaceutical treatment would make it possible to relieve the pain of these women. Endocare treatment consists of visual and auditory therapeutic procedures for pelvic‐perineal pain in patients with endometriosis. Moreover, as Endocare is not a pharmacological molecule but a digital therapy, it would not increase the consumption of pharmacological agents. An analgesic effect of Endocare lasting several hours on chronic pelvic‐perineal pain associated with endometriosis is expected. The effects of the treatment will be compare to a digital control also integrated in a virtual reality headset identical to the one distributing Endocare allowing to maintain the blindness to the patients and the investigator on the treatment received.

Nct (2021). "Endometriosis and Microvascular Dysfunction: role of Inflammation." ClinicalTrails.gov.
	Endometriosis is an estrogen‐dependent gynecological disorder associated with considerable chronic pelvic pain, pain during intercourse, and is a major cause of infertility. This disorder affects 6% ‐ 10% of reproductive age women and can be as high as 35‐50% in women experiencing pain or infertility. Endometriosis derives from the presence of endometrium‐like tissue in sites outside the uterine cavity. While endometriosis is a local inflammatory syndrome, the inflammatory process is systemic. Endometriosis is associated with higher risk of hypercholesterolemia and hypertension 8. Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk. Endometriosis a disease of inflammation and increased systemic inflammatory cytokine production, although the precise mechanisms by which localized lesion results in systemic inflammation are incompletely understood. Published data confirm an elevation of several inflammatory cytokines in the circulation of women with endometriosis. Alterations in circulating miRNAs specific to endometriosis are one mechanism causing immune dysfunction and subsequent increased cytokine expression in areas remote from the endometriotic lesions. This aberrant increase in systemic cytokine production is a highly plausible putative link to accelerated vascular dysfunction and atherosclerosis in women with endometriosis. The circulating factors LDL and oxidized LDL are two of the many biomarkers of cardiovascular and inflammatory disease of endometriosis. An important signaling mechanism through which circulating LDL and oxLDL act is the lectin‐like oxidized LDL receptor (LOX‐1). LOX‐1 is a ubiquitously expressed scavenger receptor, stimulated by oxLDL, Ang II, and other inflammatory cytokines, and inhibited by estrogen. LOX‐1 is the upstream signaling initiator of mechanisms including increased oxidant production, reduced nitric oxide (NO) metabolism, and impaired intracellular trafficking. Thus, LOX‐1 signal transduction functionally results in pronounced endothelial dysfunction.

Nct (2021). "EPPIC: easing Pelvic Pain Interventions Clinical Research Program." ClinicalTrails.gov.
	Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated. Their prolonged personal and economic costs are amplified by the frequent co‐occurrence of a cluster of centralized pain conditions (particularly irritable bowel syndrome 3 [IBS]) but also fibromyalgia [FMS], chronic headache, chronic fatigue, etc.) called Chronic Overlapping Pain Conditions (COPC). Clinically, the notion that these syndromes share a centralized pain phenotype with a fundamental disturbance in pain or sensory processing dovetails with our preliminary research showing that a novel transdiagnostic behavioral treatment emphasizing a single common mechanistic pathway (i.e. inflexible cognitive style) reduces severity of both targeted (IBS) and untargeted multisymptom COPCs that include (but is not limited to) to UCPPS, FMS, chronic fatigue, and chronic headache. If effective in a larger scale study, a transdiagnostic UCPPS treatment would offer a more efficient, accessible, and broadly useful strategy for improving chronic pelvic pain and its most frequent and complicating comorbidities. To this end, the investigators will randomize 240 UCPPS subjects (18‐70 yrs.) of any gender and race to a 4‐session version of CBT that teaches skills for self‐managing UCPPS symptoms (e.g. pelvic pain, urinary symptoms such as urinary frequency, urgency) with minimal clinician oversight (MC‐CBT) or a four‐session non‐specific education/support control (EDU). Efficacy assessments will be administered at pre‐treatment baseline and two weeks after the end of the 10‐week acute phase using the patient version of the Clinical Global Impressions Scale and validated with the physician version rated by MD assessors blind to treatment assignment. The investigators hypothesize MC‐CBT will deliver significantly greater UCPPS symptom improvement than EDU (Aim 1). Additional aims include characterizing the durability of effects 3‐ and 6 months post treatment (Aim 2). To increase the efficacy and efficiency of behavioral pain treatments, the investigators draw upon Beck's transdiagnostic cognitive model to characterize the precise cognitive procedures and corresponding operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC‐CBT induced UCPPS symptom relief relative to EDU (Aim 3) as well as baseline patient variables that moderate differential response (Aim 3) with the ultimate goal of more proactive patient‐treatment matching fundamental to the goals of personalized medicine. By applying innovative statistical modelling (e.g. dominance analysis, Randomized Explanatory Trial analyses) to study aims in the context of a rigorously designed behavioral trial, the researchers expand the portfolio of nondrug pain treatments for UCPPS and co‐aggregating COPCs to include one whose brevity, convenience, and transdiagnostic design "meets patients where they are" and addresses the practical (access, complexity, cost), clinical (breadth, durability, magnitude of effects, patient preference) and conceptual (untargeted comorbidities, non‐pain somatic symptoms) challenges that have impeded uptake and public health impact of evidence‐based behavioral pain treatments at a time when our most vulnerable high impact pain patients are in greatest need.

Nct (2021). "Erectae Spinae Block Versus Intrathecal Morphine for Postoperative Analgesis in Lumbar Surgeries." ClinicalTrails.gov.
	This study will be performed in the in the FAYOUM University hospital after the local Institutional Ethics Committee and local institutional review board approval. The study design will be double blinded retrospective controlled comparative study. A detailed informed consent will be signed by the eligible patients before recruitment and randomization. Inclusion criteria: ‐ American Society of Anesthesiologists (ASA) physical status I, II patients who will be scheduled for elective lumbar surgery for one or two levels. ‐ Age range from 18 and 70 years. Exclusion criteria: ‐ patient refusal. ‐ significant renal, hepatic and cardiovascular diseases. ‐ History of allergy to one of the study drugs. ‐ Pregnancy. ‐ Any contraindication to regional anesthesia such as local infection or bleeding disorders. ‐ Chronic opioid use, history of chronic pain and cognitive disorders. ‐ Lumbar spine lesion revision and dural tear. Randomization will be done via computer‐generated random numbers that will be placed in separate closed envelopes and will be opened by study investigators just after induction of general anesthesia. Neither the patients, the study investigators, the attending clinicians nor the data collectors will be aware of the allocation of groups till the study ends. The patients will be allocated in 1:1 ratio to one of the two groups: group erector spinae plane block (n=41), and group intrathecal morphine (n=41). Anesthesia procedure: All patients will receive 150 mg ranitidine oral tablet at the night and on the morning of the operation as a premedication. Upon arrival to the operating room, standard monitors (Electrocardiogram, Pulse oximeter, Noninvasive blood pressure monitoring) will be applied and continued all over the operation. An intravenous (IV) access will be established. General anesthesia will be performed as follows: induction will be made using IV propofol (2mg/kg), atracurium (0.5mg/kg), and fentanyl (1microgram/kg). A cuffed endotracheal tube (7‐8.5) size will be placed to secure the airway .The patients will be placed in the prone position. Maintenance of anesthesia will be made using inhalational anesthesia (isoflurane) and IV atracurium according to the patients' requirements. Block procedure: The same anesthesiologist who is experienced in US guided regional anesthesia will perform the block. In the group ESP, a high frequency linear US probe (HFL_50, 15_6MHz) will be placed vertically and nearly 3 cm lateral to the vertebra in the middle of the incision line. The transverse process and the overlaying erector spinae muscles (ESM) will be identified under parasagittal scanning A22 G,50 mm block needle (SONOTAP,Pajunk, Geisingen,Germany) will be inserted at a 30‐40° angle in the cranial to caudal direction via an in‐plane approach and advanced into the plane between the fascia of ESM and transverse process under sterile conditions. The correct needle position will be confirmed after a hydro dissection with 3 ml of isotonic saline, and then 20 ml of 0.25% bupivacaine will be injected in the interfascial plane between the rhomboideus major muscle and ESM. The local anesthetic spread will be visualized in a fascial longitudinal pattern deep to the ESM. The same procedure will be performed on the contralateral side. In the group of intrathecal morphine , a lumbar puncture will be done in the lateral position via a midline approach into the level of the vertebra which exists in the middle of the incision with complete aseptic condition using 25 gauge Quincke spinal needle to give 0.3 mg of morphine (preservative free form) suspended in 0.4 ml of normal saline . Anesthesia will be discontinued at the end of the surgery and the patients will be extubated after return of spontaneous respiration .All patients will be followed for 1 hour in the post anesthesia care unit (PACU) then discharged to the ward. In the postoperative period we will give the patients multimodal analgesic regimen as following : a) paracetamol 1000 mg IV 3 times/day, b) dexketoprofen 50 mg IV once/day, c) V pethidine 0.5mg/kg as a rescue analgesic on demand. Postoperative pain will be evaluated using a visual analogue scale (VAS 0: no pain, 10: worst pain ever) at 0 hours postoperative in PACU, then at postoperative 2., 6.,12.,24., and 48 hours at the ward by a research assistant who will be blinded to the study groups. Pethidine IV 0.5 mg/kg will be given as a rescue analgesic when the VAS score will be more than 3. The amount of pethidine consumption will be recorded between 0‐12., 12‐24., and 24‐48 hours. The following criteria will be recorded and compared between the two groups : demographic data ( Age, Weight, sex and height) , ASA classification ,mean operative times (min), VAS scores , time to the first rescue analgesic (h) ,intraoperative fentanyl consumption(mg),postoperative opioid consumption ,sedation score, hemodynamics intraoperative and postoperative ( blood pressure ,heart rate and spo2 ) and complications. Complications include complications related to the block and the surgery (nerve damage, local anesthesia toxicity, bleeding, infection, and thromboembolism) and complications related to the general anesthesia , intrathecal morphine and IV opioids (respiratory depression , nausea and vomiting, urine retension, hypotension , bradycardia, pruritus, constipation and dizziness ).9 Primary outcome measures: The mean VAS score (score 0 =no pain and 10 =worst pain ever ) in the two groups of the study. Secondary outcome measures: The secondary outcome will include the following : demographic data ( Age, Weight, height, body mass index) , ASA classification ,mean operative times (minutes), time to first rescue analgesic (minutes) ,intraoperative fentanyl consumption(micrograme),postoperative opioid consumption ,sedation score, hemodynamics intraoperative and postoperative ( blood pressure ,heart rate and spo2 ) and complications. Complications include complications related to the block and the surgery (nerve damage, local anesthesia toxicity, bleeding, infection, and thromboembolism) and complications related to the general anesthesia, intrathecal morphine and IV opioids (respiratory depression, nausea and vomiting, hypotension, bradycardia, pruritus, constipation and dizziness). Statistical analysis and sample size estimation : Sample size was calculated using G*power version 3.1.9.4. Previous similar studies indicated that a minimal sample size of 37 patients in each group will be needed to achieve a power level of 0.80 , alpha level of 0.05(two tailed) , will a medium effect size of 0.66 for the VAS score at 24 hours. Estimating that 10% of patients may drop out of the study due to different reasons , sample size was increased to 82 patients (41 in each group).10 Statistical analysis will be performed using SPSS version 21.0 (IBM,Armonk,NY,USA).Data are presented as mean (SD) , median [interquartile range (IQR) ], or number of patients (%) . Distribution normality will be assessed using the Kolmogorov_Smirnov test. Comparisons between groups will be made using independent t_test or Mann_Whitney U test , as appropriate. Categorical variables will be analyzed using chi_square test or Fisher exact test. A p_value less 0.05 was considered statistically significant.

Nct (2021). "Estradiol and Progestrone Levels Following Frozen Embryo Transfer." ClinicalTrails.gov.
	Enrolled women will be randomized based on their ovulation pattern. Ovulatory women will be randomized to either natural cycle or estradiol + progesterone substituted cycle treatment for FET. Anovulatory women will be randomized to either estradiol + progesterone substituted cycle or gonadotropin stimulated cycle treatment for FET. Included women will undergo blood testing every two weeks for serum estradiol and progesterone levels until gestational age 9+6. Routine vaginal ultrasounds will be perfomed as well as additional pregnancy ultrasounds. Secondary obstetric outcomes will be investigated using the womens medical journals. All the treatments are considered standard treatments for FET.

Nct (2021). "Estrogen and Platelet Rich Plasma in Treatment of Atrophic Vaginitis." ClinicalTrails.gov.
	Oestrogen deficiency affects many organs such as the genitourinary system. Genitourinary involvement causes untoward symptoms of atrophic vaginitis including dryness, burning, dyspareunia, vulvar pruritus, and discharge For this reason, many investigations have been performed to find out effective, safe, and acceptable therapeutic methods for atrophic vaginitis. Although systemic administration of estrogen can improve the localized symptoms of atrophic vaginitis, women are often reluctant to use systemic hormone replacement therapy and prefer local administration of estrogen. Vaginal application of estrogen has been considered an effective treatment of atrophic vaginitis. The effects of PRP treatment have been evaluated in many clinical conditions, including wound healing, hair repair, skin regeneration [9], vulvar lichen sclerosis, stress urinary incontinence, episiotomy scars, and lubrication aging in the vagina. It can take at least 12 weeks to determine the final effects of treatment with PRP Population of Study It includes 100 pt. complaining of atrophic vaginitis it will be divided into two groups, each group will contain 50 pt Methodology in detail: Patients of the first group will receive vaginal estrogen cream one tube every night for 14 nights; then, one tube 2 nights in 1 week (two tubes every week) for 10 weeks. The second group will receive PRP injection every 3 weeks for 4 times. PRP will be administered to the anterior vaginal wall using 27‐G needles once every 3 weeks for 4 times and PRP is mainly injected into the clitoris or the anterior wall of the vagina to increase the tactile sensitivity of the injection site.

Nct (2021). "Evaluating the Management of Chronic Pelvic Girdle Pain." ClinicalTrails.gov.
	The investigators will undertake a multi‐centre feasibility RCT, randomising participants to receive either the "pelvic support shorts" plus standardised information and exercises (intervention) or standardised information and exercises alone (control). The investigators will recruit 60 women from the South West of England who are experiencing chronic (≥3 months) and severe pelvic girdle pain following pregnancy. Following screening and consent, baseline assessment will be undertaken using a range of patient‐reported measures: pain, depression, continence, function, quality of life, health/social care and patient resource use. Women will randomly allocated to intervention or control. Two weeks following randomisation, all participants will attend a physiotherapy session via web‐conference to receive standardised information and suggested exercises. In addition, intervention group participants will receive two pairs of the pelvic support shorts. In line with usual physiotherapy practice, all participants will receive a follow‐up review session via web‐conference, approximately 10 days later. Throughout the study timeframe, medication usage and pain rating scale scores will be completed by the women, on a fortnightly basis, via web‐based self‐report questionnaires. Additionally, at 12 and 24 weeks all baseline patientreported measures will again be collected. A qualitative sub‐ study, involving interviews (telephone or web‐based) will explore participant experiences of wearing (patient) and providing (physiotherapists) the support shorts, and of the study itself. The Population The investigators shall recruit women, 18 and over, experiencing chronic and severe pelvic girdle pain. This pain must have started or been aggravated during pregnancy and have continued for at least three‐months following childbirth. The pain is 'severe' if it causes walking or stair climbing to be bothersome and scores positively on a range of pain provocation tests. Potential participants will be excluded if they have pathologies which cause pelvic girdle pain (e.g. infection, trauma), are currently pregnant, report an allergy to Lycra, or where pain has persisted for > two years following pregnancy so that the investigators can limit the risk of other pathologies being the origin of pain. Intervention and Control. All treatment will be provided by NHS physiotherapists at two web‐based sessions. Control Group. Both groups will receive standardised advice on management of pelvic girdle pain, through a discussion centred around 'Guidance for Mothers‐to‐be and New Mothers: Pregnancy‐related Pelvic Girdle Pain' booklet (https://pogp.csp.org.uk/system/files/pogp‐pgppat_3.pdf). This publicly available, specialist physiotherapy approved, standardised leaflet, provides information reflective of current best practice. The participant can use this as an ongoing resource. The physiotherapist will teach participants a standardised programme of exercises, typical of those provided within usual physiotherapy practice. Written explanation/illustrations of these exercises will be provided and the women asked to undertake these at home, three times/week. Intervention Group In addition to the above, women in the intervention group will be fitted with the customised pelvic support shorts (DM Orthotics Ltd, https://www.dmorthotics.com). Prior to the first physiotherapy session, those women allocated to the intervention group will have recieved the support shorts in the post together with standardised written information on wear time/washing. At the first physiotherapy session (one hour), the woman will be asked to try them on so that the physiotherapist can review the fit and comfort of the shorts. The physiotherapist will reinforce the written advice about wear time and care of the shorts, and answer any queries / brainstorm any issues. At session two (30 minutes), 10 days later, the physiotherapist will review the fit and wearing of the shorts, problem solve any issues that have arisen, and review exercises to ensure they are eing performed correctly. After these two appointments all participants will be continue to self‐manage the condition for the remainder of the trial. Participants are not prevented from accessing further healthcare. The trial is capturing this information through a resource use questionnaire which is collected at baseline, 12 and 24 weeks. Outcomes and their measurement. In our feasibility trial, participants will be requested to complete a range of self‐report outcome measures via a mobile/web app. Our PPI discussions led us to choose self‐report questionnaires, completed via a web‐based application, to minimise burden (time and travel) on our participants who are experiencing significant pain. This is particularly important since driving and travelling frequently exacerbated this pain. Some women may prefer paper versions, returned by post. In line with the remit of a feasibility trial, the investigators include a variety of measures to determine their performance in the context of this trial and, along with trial participants and our PPI group, to identify those that may be most appropriate for the definitive trial. All are standardised patient‐report measures which have been previously used in studies investigating pelvic girdle pain. Demographic data will be collected at screening (age, weight, number of pregnancies, severity/duration/site of pain). Additional clinical data will be collected at baseline: medication, week of delivery, length of labour, induction required, mode of delivery, episiotomy/perineal tear, baby's gender and weight, presence/absence of back pain prior to pregnancy. All outcome measures will be completed at baseline and 12 and 24 weeks following the first intervention session, apart from the Pain Rating Scale and medication usage which will be completed fortnightly. Recruitment Procedure Women will be recruited from three NHS Trusts across the Southwest of England: 1. Royal Cornwall NHS Foundation Trust, Cornwall Partnership NHS Foundation Trust, and University Hospitals Plymouth NHS Trust. Physiotherapists in musculoskeletal outpatient and women's health services will be key recruiters due to their contact with women experiencing chronic pain following pregnancy. They will raise study awareness and provide patients with study information leaflets. The Clinical Research Network (CRN) staff will undertake a database search, eligibility check, and mail‐out to potential participants. With the clients' consent, the CRN nurse will inform the research team of potential participants via a study specific email account. The research team will telephone/email the potential participant to undertake initial screening and, if still apparently eligible, book a web‐based screening appointment. 2. Research active general practices with an on‐site First Contact Physiotherapy Practitioner. CRN staff will undertake a database search and mail‐out to potentially eligible patients, inviting them to express an interest in the trial. With the consent of those interested, names will be forwarded to the research team. The study will be advertised in local children's centres and on social media [Mumsnet; facebook pages of the Pelvic Partnership Pelvic Girdle Pain Support Group, National Maternity Voices, National Childbirth Trusts], and via relevant hospital web‐site and twitter accounts which advertise research trials. A research physiotherapist will undertake the web‐based screening/measurement for shorts and baseline assessments, in separate sessions independent of treatment. The nature of the self‐report measures ensures the assessor will not influence participant responses. Participants will be asked not to discuss their treatment with the researcher. Randomisation and blinding. Following baseline assessment, the research physiotherapist will enter key participant details (number of pregnancies, pain onset/duration) into the Clinical Trial Unit's (CTU) web‐based randomisation system and immediately receive that participant's group allocation. Randomisation will be stratified by centre an resence/absence of back pain pre‐ pregnancy. An automatic email will be sent by the CTU to the NHS‐treating physiotherapist to inform them of the woman's group allocation, and enable them to schedule an outpatient appointment approximately two weeks (+/‐1 week) later. A second email with the patient's measurements will be sent to DM Orthotics Ltd to allow manufacture of the customised shorts. Sample size The investigators aim to recruit 60 participants over 7‐months. As this proposal is for a feasibility trial, a sample size calculation is not appropriate. Instead, the investigators aim to sample sufficient participants to provide the operational experience to conduct a larger trial and to provide data to inform future sample size calculation. EMBEDDED QUALITATIVE COMPONENT. Qualitative research to explore "real‐life" experience is important in order to understand and learn from participants about whether trial processes, the intervention and outcome measures are acceptable. The investigators will therefore undertake interviews with a sub‐sample of women to explore the: ‐ acceptability of trial methods across both trial arms ‐ acceptability (comfort, wear‐time) of the support shorts ‐ impact the intervention may/may not have on women's lives. ‐ adherence to the exercise regime over the course of the trial Ten purposively sampled participants from the trial will include 5 trial participants randomised to the control group and 5 participants from the intervention group. These will include women receiving interventions from both the secondary care (RCHT & UHP) and primary care sites (GP practices). This will be run through individual one off semi‐structured telephone interviews using a topic guide. Interviews will occur at the end of the trail period. Five NHS physiotherapists (from secondary and primary care sites) involved within the trial will be purposively sampled to provide information on the acceptability of the trial methods across both trial arms. ECONOMIC EVALUATION. The investigators will estimate the resource requirements of the intervention, and establish the framework for a future cost effectiveness analysis alongside a full RCT. Data on intervention resources will be collected about participant‐level contact and non‐contact time, and training for delivery staff. Participants will self‐report health, social and wider care resource use, using the Resource Use Questionnaire from our antenatal study and adapted for this trial by our PPI Group.

Nct (2021). "Evaluation of a Hysteroscopic Method With Vaporization in the Hysteroscopic Treatment of Submucosal Uterine Fibroids." ClinicalTrails.gov.
	Operative hysteroscopy (OH) is an endoscopic technique for the treatment of benign intrauterine lesions and in particular uterine fibroids. The limit of this technique is the duration of the operation which is correlated with the operative risks. Thus, when there is a large fibroid or several fibroids, this technique can sometimes not be used or require several sessions. Today there is a new technique of HO that theoretically allows a gain in operative time. There are few comparative studies showing a clinically interesting gain in operating time. The aim of this study is to compare the operative time between the classical HO technique by resection and the vaporization technique. This is a randomized, single‐center study. The study population corresponded to women aged over 18 years requiring operative hysteroscopy for fibroids. After obtaining informed consent, patients will be randomized into two groups: a vaporization hysteroscopy group and a resection hysteroscopy group. The primary endpoint will be operative time. The secondary endpoints will be intraoperative characteristics and complications (amount of distension fluid used, cervical injury, uterine perforation), immediate postoperative data (pain) and medium‐term data (postoperative synechiae). The starting hypothesis is that the technique of hysteroscopy by vaporization would reduce the operative time by 30%. The number of subjects required per group will be 27 patients, or 54 patients in total over 24 months. The expected results are a significant decrease in operative time with the vaporization hysteroscopy technique. This would be important because the reduction in operative time is associated with a reduction in complications of operative hysteroscopy and the possibility of treating larger fibroids with this technique.

Nct (2021). "Exercise as a Preventive Agent to Combat Immobility in Patients With Ovarian or Endometrial Cancers Receiving Chemotherapy." ClinicalTrails.gov.
	This research study is a randomized controlled trial that will compare an exercise group to a control group on lower extremity function, CIPN, and inflammatory markers in ovarian or endometrial cancer patients undergoing first‐line chemotherapy after surgery. The names of the study interventions involved in this study are/is: ‐ Aerobic and resistance exercise; virtually supervised 16‐week aerobic and resistance exercise performed at home via Zoom ‐ Attention control for 16 weeks, home‐based stretching The research study procedures include: screening for eligibility and study interventions including evaluations and follow up visits. It is expected that about 30 people will take part in this research study.

Nct (2021). "An Exploratory Investigation of Dietary Supplementation and Its Effect." ClinicalTrails.gov.
	This will be a 2‐arm randomized, double‐blinded, placebo‐controlled study.

Nct (2021). "FitEx for Endometrial Cancer Survivors." ClinicalTrails.gov.
	Uterine cancer is the leading form of gynecologic malignancy in the United States. Currently, there are more than 600,000 EC survivors in the United States, and that number is expected to grow. Endometrial cancer (EC) is caused by excess estrogen, which acts as an oncogenic signal. Postmenopausal women with obesity have increased production of estrogen and are at an increased risk of developing type I EC. Endometrial cancer was one of the first types of cancer to have an established relationship with body mass index (BMI). This relationship is linear and dose‐dependent with BMI and can be explained by excess estrogen production . In women, adipose tissue is able to generate a form of estrogen known as estrone. Excess adipose tissue leads to increased production of estrone, which proliferates endometrial growth. For every five unit increase of BMI, the production of excess estrogen drives a 50% increased relative risk of developing EC. Approximately 62% of American women are overweight or obese, putting them at increased risk of developing EC, the sixth most common cancer type in women in the United States. As the obesity rate in America continues to rise, the incidence of EC cases follows similar patterns. Between 2003 to 2015, the number of new EC diagnoses has increased by 13%, and continues to increase by 1% in following years. The National Cancer Institute predicts that nearly 60,000 new cases of EC will be diagnosed in 2021 and estimates that nearly 3% of women will be diagnosed with EC in their lifetime. Fortunately, EC patients have relatively strong outcomes compared to other cancer types, as patients have an approximately 80% 5‐year survival rate. However, a vast majority (70 ‐ 90%) of type 1 EC survivors are obese. Five years after diagnosis, women with EC are more likely to die from cardiovascular disease and its risk factors, such as obesity and type 2 diabetes, than from EC. EC survivors with obesity report higher rates of depression and lower quality of life outcomes (sleep quality, self‐esteem, fatigue, daily stress, etc.) than their non‐obese counterparts. These outcomes worsen as BMI increases. Addressing the role of obesity in EC survivors by encouraging physical activity is critical to improving optimal longitudinal care to survivors suffering from declining quality of life. Regular physical activity is associated with decreased levels of circulating estrogens in post‐menopausal women and moderate physical activity in adulthood has been associated with reduced rates of developing endometrial cancer. As measured by a meta‐analysis of physical activity interventions in participants with cancer, physical activity has established improvements to quality of life, fatigue, and physical functioning. The connection between physical activity and BMI, morbidity, mortality, and improved quality of life outcomes is well supported. Despite this connection, only 1% of EC survivors meet all of the American Cancer Society guidelines for diet, exercise, and smoking recommendations. To increase the number of EC survivors meeting these guidelines, various exercise interventions have been developed to encourage EC survivors to increase physical activity and ultimately, improve their BMI. However, existing interventions for EC survivors, geared towards improvements in BMI, have not been found to be efficacious in eliciting long‐term changes in behavior with respect to weight loss. Because targeting weight loss was not effective in prior interventions, a successful intervention should target increasing physical activity rather than explicitly decreasing BMI. In breast cancer survivors, a similar demographic, many existing physical activity interventions are unsuccessful due to their focus on high intensity activities and due to the burden on participants to exercise together in person. In order to address pitfalls in prior physical activity studies, an ideal intervention should also target improvements to physical activity using lighter, ergonomically sound movements in a remote setting. While partici nts report in‐person physical activity as a barrier, various exercise studies have demonstrated that increasing social support is a powerful motivator of long‐term behavior change, including adherence to physical activity. EC survivors surveyed in Canada report wanting a program that incorporates social support into an intervention. In breast cancer survivors, a group‐dynamics based intervention achieved improvements in physical activity outcomes that persisted six months post‐intervention. Prior successful interventions have utilized social support but often require substantial physician engagement. While patients are more likely to engage with an exercise intervention if encouraged by their physician, oncologists noted barriers to promoting healthy behaviors in patients with obesity include lack of training in health promotion and even fear of overwhelming patients with health‐promoting advice. Past ECS research that has shown successful and lasting improvements to behavior include weekly 1‐on‐1 physician calls and personalized telehealth communication, and cancer center exercise classes. In these interventions, an implicit cost is associated with staffing or availability (both for the participant and for the intervention facilitator). Taken together, an intervention that can facilitate the sense of groupness and be delivered virtually is optimal due to budget constraints on healthcare centers, geographical constraints of participants, and the current COVID‐19 pandemic. Surveyed EC survivors prefer gentle, group‐based, walking exercises that function as support groups and exercises that they can do from home, but note barriers to adherence include access, fatigue, and pain. Yoga has been shown to decrease cancer‐related fatigue, improve mobility, and increase mindfulness among cancer patients. Weekly yoga is a potential target to address barriers of exercise but has not been explored in detail in the EC patient population. In a focus group of sixteen gynecologic cancer survivors, yoga was viewed favorably by survivors and is a newly developing target for increased physical and psychological well‐being. Yoga improvements have been shown in a range of health conditions including post‐menopausal symptoms, cancer, heart disease, and even long‐term improvements to BMI. The most common demographic for yoga practitioners is White, middle‐aged women and practitioners strongly endorse the benefits of yoga on mindfulness, social support, and coping with stress. Prior work in EC survivorship has demonstrated that increased BMI has a negative impact on quality of life, an outcome that yoga has improved in similar populations such as breast cancer survivors. Goal setting and behavior tracking are two key behavioral psychology principles that encourage and promote improvements in exercise and dietary habits in obese adults, and successful interventions should incorporate these principles as components to see greater success. FitEx is a virtual, scalable, evidence‐based walking program that can be easily modified to include other exercises such as yoga. FitEx has shown significant maintenance of physical activity changes six months post‐intervention. FitEx participants join a team, led by regional facilitators and local team captains, and set a physical activity and dietary goals throughout the eight week intervention. Participants have the opportunity to meet with others weekly for remote, guided exercise demonstrations. Participants are able to see if their goals are being met each week as self‐monitoring is built into the FitEx interface, creating a sense of real time feedback. The program was developed for community‐dwelling adults and its impact on cancer survivors has yet to be tested. Thus, FitEx is an intervention that meets the five dimensions of RE‐AIM: Reach, Effectiveness, Adoption, Implementation, and Maintenance, such that small changes to FitEx do not diminish any of these dimensions and overall program success. Because FitEx is a validated program of measuring daily physical acti ty adherence which incorporates a low‐dose of social support, it can easily be modified to target specific populations. Additionally, FitEx can be modified to include different exercises, such as yoga, which are viewed favorably by ECS. The present study seeks to determine whether a modified FitEx intervention geared towards survivorship or yoga improves outcomes in physical activity adherence and in quality of life in EC survivors. As measured through FitEx, the yoga intervention will provide a remote workout regimen led by a registered yoga instructor. The control FitEx condition will include standard weekly meetings that currently take place in FitEx. Both arms incorporate walking as the predominant form of exercise and may include any other exercises of the participant's preference according to their goals. As a modified, tailored intervention for ECS, FitEx has the potential to improve physical activity adherence and quality of life in ECS. The overall objective of this work is to tailor FitEx for ECS, with the goal of improving physical activity, as measured by step count, for both groups. Participants will be randomized to EC‐ tailored FitExEc (control) or FitExEC+yoga (intervention). The study hypotheses are (1) FitExEC and FitExEC+ yoga are feasible and acceptable (2) participants in both conditions will have improved weekly step count compared to baseline and (3) participants in the yoga‐tailored condition will have greater improvements in quality of life compared to the ECS control condition. The study's primary aims are feasibility and acceptability. The investigators will assess using recruitment statistics. The study's secondary aims are efficacy related to physical activity improvement (measured through pedometers (step count) and subjectively through self report) as well as quality of life, fear of cancer recurrence, exercise preferences, social support, self‐compassion, and exercise class satisfaction. The investigators expect that both group‐based programs will improve physical activity behaviors during the 8‐ week intervention, while the yoga‐tailored group will exhibit improved secondary outcomes. The study's complementary aims will assess psychosocial factors, long‐term outcomes, and barriers to implementation.

Nct (2021). "Fractionated CO2 Laser With and Without Clobetasol for Treatment of Vulvar Lichen Sclerosus." ClinicalTrails.gov.
	This is a randomized placebo‐controlled trial design to determine whether combining FxCO2‐laser with the traditional therapy of clobetasol propionate 0.05% ointment (combined treatment) as compared to FxCO2‐laser and placebo ointment (FxCO2‐laser only) will improve treatment response in women undergoing FxCO2‐laser for vulvar lichen sclerosus. Primary objective: To evaluate if women with LS who undergo FxCO2 laser therapy and concomitant TCS (clobetasol group) have higher treatment success (defined as a MCID of a ≥16 point improvement in Skindex‐29 questionnaire) than those who undergo FxCO2 laser and placebo ointment (placebo group). ‐ Hypothesis: A higher proportion of women randomized to clobetasol will achieve treatment success as compared to those randomized to placebo. ‐ Approach: The proportion of women in each cohort who obtain a ≥16 point improvement in Skindex‐29 validated questionnaire score from baseline to final visit will be compared. Secondary objectives: To compare change in pre‐ and post‐treatment scores on validated questionnaires measuring vulvovaginal symptoms, sexual function, lower urinary tract function, and genital self‐image between the clobetasol group compared to the placebo group. ‐ Hypothesis: Women randomized to clobetasol will demonstrate an equal or greater improvement on validated quality of life questionnaires measuring vulvovaginal symptoms, sexual function, lower urinary tract function, and genital self‐image as compared to women randomized to placebo. ‐ Approach: Change scores will be calculated to determine change per participant over the treatment period and mean change scores will be compared between cohorts.

Nct (2021). "GnRH Agonist Plus Hormone Replacement Therapy vs Hormone Replacement Therapy on IVF Outcomes." ClinicalTrails.gov.
	The study is conducted at Arash Women's Hospital on all women undergoing the frozen embryo transfer cycle. Patients who signed informed consent will be randomly divided into two groups. The first group will receive GnRH agonist plus hormone replacement therapy for endometrial preparation. Group 2 will receive hormone replacement therapy. The random allocation and final outcome of the study will be assessed by a person who is unaware of the study process. Also, the statistician will be unaware of the study process

Nct (2021). "Gonadotropin Releasing Hormone Agonist (GnRHa) Versus Estrogen and Progesterone for Luteal Support in High Responders." ClinicalTrails.gov.
	The administration of human chorionic gonadotropin (hCG) for final oocyte maturation is an accepted practice in in vitro fertilization (IVF) treatments. However, in high‐responder patients, it increases the risk of ovarian hyperstimulation syndrome (OHSS) due to its longer half‐life compared to the naturally secreted Luteinizing Hormone (LH) as well as increased synthesis and secretion of vasoactive substances. Gonadotropin releasing hormone agonist (GnRHa) triggering, as an alternative to hCG triggering for final oocyte maturation in antagonist protocols, enables substantial decrease of this complication in high responders. However, the main disadvantage of using GnRHa for induction of oocyte maturation is significantly lower pregnancy rates compared with hCG triggering. The primary hypothesis is luteal insufficiency due to increased luteolysis. In order to preserve a high pregnancy rates after GnRHa triggering, several approaches for luteal‐phase rescue have been investigated, including low‐dose hCG boluses, intensive P and E2 supplementation, and a ''freeze‐all'' approach with frozen‐thawed embryo transfers at subsequent cycles. Several previous case reports have demonstrated that inadvertent administration of GnRH agonists during the luteal phase doesn't harm pregnancies achieved through IVF and moreover might even support implantation. The mechanism by which GnRH agonist improve implantation rates is unknown. Several hypotheses were suggested including promoting corpus luteum maintenance by secretion of LH from pituitary gonadotropin cells, a direct effect on the endometrium and the embryo through GnRH receptors and regulatory effect on hCG secretion by the placenta at the preimplantation phase. In 2004, Tesarik et al, conducted a prospective randomized trial including 276 oocyte recipients. Oocytes from each individual donor were divided to two recipients, one of whom received a single dose of a GnRH agonist (0.1 mg triptorelin) 3 days after embryo transfer and the other received placebo at the same time. Of note, the endometrium was prepared by oral estradiol valerate treatment following by vaginal progesterone (Utrogestan) as widely accepted. The results demonstrated significantly higher implantation and live birth rate in the group treated with GnRH agonist compared to the control group with significantly higher twin pregnancy rates while no difference in miscarriage and abortion rates was observed between the two study groups. The authors concluded that GnRH agonist administration at the time of implantation has a positive effect on embryo developmental potential. It's important to note that this study evaluated the effect of a single dose of GnRH agonist in addition to a conventional luteal support in a population of oocyte recipients that are not at risk for OHSS and tend to have higher implantation and pregnancy rates also without GnRH agonist supplementation. A study by Pirard et al. was the first to evaluate the administration of GnRH agonist alone for luteal support compared to compared to the standard treatment with vaginal progesterone. The study group included 35 patients who were treated with antagonist protocol. Intranasal GnRH agonist (Buserilin) was given for final oocyte maturation and luteal support was achieved by administration of intranasal GnRH agonist for up to 16 days after the oocytes retrieval. The control group included 18 women treated with a long GnRH protocol for pituitary suppression. Final oocytes maturation was achieved by administration of 10000 units of hCG and vaginal progesterone was used for luteal support. Implantation and pregnancy rates were higher among the study group compared to the control group however, no statistical significance was achieved. Progesterone levels on day 5 were significantly lower while LH levels were significantly higher during all the luteal phase in the study group compared to the control group. The authors concluded that intranasal administration of Buserelin is as effective as standard progesterone treatment for providing luteal hase support in IVF/ICSI antagonist protocols. To our knowledge, the only study, so far that evaluated the efficacy of GnRH agonist treatment for luteal support in high responder patients with increased risk for OHSS was conducted by Bar‐Hava et al. It included 46 women at risk for OHSS that were treated with GnRH antagonist protocol for pituitary suppression. The final oocyte maturation was achieved by GnRH agonist (Triptorelin) and a daily intranasal GnRH agonist (Nafarelin 200 micrograms twice daily) was administered for luteal support for two weeks following the oocytes retrieval. 52% clinical pregnancy rates were obtained while no cases od OHSS or other substantial adverse effects were observed. The main disadvantage of the study is the lack of a comparison to a control group. To the best of our knowledge, no study so far compared administration of GnRH agonist at the same protocol described by Bar‐Hava et al. to intensive estrogen and progesterone treatment for luteal support among women treated with GnRH antagonist protocol and GnRH agonist triggering for final oocytes maturation. A randomized controlled trial in an infertility population at increased risk for OHSS, will enable us to evaluate the efficacy of GnRH agonist treatment compared to standard treatment for luteal support and to determine the best treatment approach in the high responder population undergoing a fresh embryo transfer new approach undergoing a fresh embryo transfer following GnRHa triggering. The aim of the current study isto compare the efficacy of GnRH agonist versus estrogen and progesterone supplementation for luteal support in high responders undergoing fresh embryo transfer following GnRHa triggering.

Nct (2021). "Goserline Acetate VS Dienogest in Endometriosi." ClinicalTrails.gov.
	The study will be a clinical trial study of 12‐week trial of GnRH (zoladex 3.75mg) injection once every 4 weeks and Visanne (dienogest 2mg) oral once daily for 12 weeks in patients confirmed endometriosis by laparoscopic surgery. Pretreatment assessment, the patients will be questioned about their pelvic symptoms (dysmenorrhea, nonmenstrual pelvic pain, and deep dyspareunia) after taking full history and examination , The study will investigate and evaluate possible early, long side effects and efficacy of treatment to controlling the pain.

Nct (2021). "Haloperidol, Droperidol, Ondansetron in Cannabis Hyperemesis." ClinicalTrails.gov.
	The purpose of this study is to compare two commonly used agents for the treatment of cyclic vomiting to see if one agent is inferior to the other in time to improvement in symptoms, need for repeat or rescue medications, treatment failures and complications/side effects.

Nct (2021). "HIIT vs MICT During Pregnancy and Health and Birth Outcomes in Mothers and Children." ClinicalTrails.gov.
	Regular exercise during pregnancy and postpartum leads to health benefits for mother and child. Inactivity during pregnancy and after delivery is now treated as risky behavior. Physically active pregnant women significantly less often suffer from, among others, gestational diabetes, excessive weight gain, lipids disorders, hypertension, preeclampsia, depressive symptoms, functional and structural disorders, including stress urinary incontinence, back pain or diastasis recti abdominis (DRA). Prenatal physical activity reduces the risk of premature delivery and miscarriage, fetal macrosomia, complications in labor or the risk of metabolic disorders in children. High‐intensity interval training (HIIT) has become one of the most popular trends in the fitness sector. The effectiveness of HIIT on a number of health indicators has been proven in various populations but limited data are available on HIIT during pregnancy. The first hypothesis is that the HIIT, implemented during pregnancy and after childbirth, as a stronger exercise stimulus, will have a better impact on selected biological and psychological parameters of mothers, as well as on selected health parameters of their children, compared to the MICT (moderate intensity continuous training). Therefore, it promises better preventive effects on pregnancy complications and ailments as well as non‐communicable diseases occurring in these populations. In the second hypothesis, it was assumed that HIIT and MICT implemented during pregnancy and after childbirth, tailored to the specific needs of the perinatal period, will not differ in the effectiveness of maintaining normal functional parameters in women, including prevention of urinary incontinence, back pain, DRA, etc. Pregnant women who apply for the study will be divided into three groups: those attending the HIIT, MICT or educational programs. During the study, the participants will be under standard obstetric care. As comparative groups, non‐pregnant women will be also recruited. The investigators will collect data on selected biological, functional and psychological parameters in the study women at each trimester of pregnancy, during the puerperium and one year after childbirth. The data from the medical documentation on the course of childbirth and the assessment of the new‐born, as well as the results of preventive examinations in the study women's children aged one, two, four and six years will be also analyzed.

Nct (2021). "How Does Mindful Mood Balance for Moms Work?" ClinicalTrails.gov.
	Mindfulness‐based cognitive therapy (MBCT) prevents depressive relapse and reduces residual depression symptoms among adults with recurrent depression not currently in episode. Women in perinatal or early parenting years constitute a significant portion of this at‐risk population with a history of depression for whom MBCT was designed. Novel delivery formats that provide access to core knowledge and skills of MBCT could increase public health impact‐particularly for perinatal or early parenting women‐but it is unclear whether such formats have comparable mental health outcomes and changes in putative targets as in‐person MBCT. In the present study, we planned to randomize 60 pregnant or early parenting women with a history of major depression and current residual depressive symptoms to MMB for Moms, a web‐based course that teaches skills from MBCT customized specifically for pregnant and postpartum women, or waitlist control. We planned to address the following specific aims: Aim 1. We evaluated the extent to MMB for Moms was associated with significant reduction in residual depression symptoms as compared to WLC. We predicted the rate of change in depression symptoms across the study would be greater on average for participants randomized to MMB for Moms relative to those randomized to WLC. Aim 2. We evaluated the extent to MMB for Moms significantly engaged the putative target of decentering as compared to WLC. We predicted the rate of change in decentering across the study would be greater on average for participants randomized to MMB for Moms relative to participants randomized to WLC. Aim 3. We evaluated the extent to MMB for Moms significantly engaged the putative target of self‐compassion as compared to WLC. We predicted the rate of change in self‐compassion across the study would be greater on average for participants randomized to MMB for Moms relative to participants randomized to WLC.

Nct (2021). "Hypnotic Intervention for Women With Chronic Pelvic Pain." ClinicalTrails.gov.
	Design: Pilot Randomised Control Trial Methods: Twenty women with persistent pelvic pain completed assessment questionnaires and were recruited from a variety of social media sites related to persistent pelvic pain and randomly allocated to either control or hypnotic intervention groups. The intervention group completed a seven week online hypnotic intervention. The control group received no intervention. Both groups completed assessment and concluding questionnaires related to demographic information and the outcomes of interest. This included measures for anxiety, depression, pain, coping styles, pain related disability, pain catastrophizing and suggestibility. The results of the intervention and waitlist control groups were compared using linear mixed‐effects modelling. Suggestibility was screened for at baseline using the Short Suggestibility Scale, and included in a secondary set of linear effects modelling.

Nct (2021). "Ibuprofen Versus Indomethacin Following Emergent Cerclage Placement." ClinicalTrails.gov.
	Cervical insufficiency is defined as painless cervical dilation in the second trimester. Cervical insufficiency can ultimately lead to second trimester loss of pregnancy. Cerclages are utilized in pregnancies affected by cervical insufficiency in order to prolong gestational latency. There have been several studies investigating the efficacy of perioperative medications for cerclage placement and the effects they have on gestational latency. Some such studies have found that perioperative indomethacin in combination with antibiotics have significantly increased gestational latency when compared to placebo. Indomethacin has traditionally been the tocolytic of choice with cerclage placement. At our hospital, ibuprofen has been the tocolytic of choice for cerclage placement secondary to pharmacy availability. Our study aims to evaluate whether gestational latency differs among patients undergoing emergent cerclage whether they receive perioperative ibuprofen or indomethacin.

Nct (2021). "The Immersive Experience of Virtual Reality During Chemotherapy in Patients With Early Breast and Gynecological Cancers: the Patient's Dream Study." ClinicalTrails.gov.
	"Patient's dream" study is a two‐arm randomized controlled trial that will be conducted at Regina Elena National Cancer Institute, IRCCS (Rome), from April 2019 to January 2020. Before starting the first course of chemotherapy, patients will be randomly divided to receive the VRE (VRE arm) as "distraction therapy", or to entertain themselves with conventional means such as listening to music, watching a mobile program, reading newspapers, books, magazines or also doing nothing, according to the patient's preferences and for the entire duration of administration of the first CT cycle (control arm). A clinical team composed of three oncologists, three psychologists, one nurse and one expert VR operator will support the patients involved in the study. The primary aims were the assessment of psychological distress, anxiety and quality of life between the two study arms. Secondary endpoints were the perceived time during the first course of CT and the acute and late toxicity. The study will conduct in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments and within the protocol approved by the Central Ethics Committee (Trial registration number: RS 1105/18). A written informed consent will obtain from all participants included in the study.

Nct (2021). "Impact of Specific Monitoring of Intraoperative Analgesia Under General Anesthesia on Chronic Pain After Ovarian Cancer Surgery." ClinicalTrails.gov.
	Prior to carrying out the research, the informed consent of the person must be obtained after being informed of the purpose of the research, its conduct and duration, benefits, potential risks and constraints of the study. Before inclusion,all eligibility criteria will be verified, VAS pain score and VAS anxiety will be performed. The surgical procedure for ovarian carcinoma will be performed by laparotomy and the intraoperative monitoring of nociception wil depend of the randomization arm : Intraoperative ANI monitoring of nociception (experimental arm) versus no specific monitoring of nociception (control arm). The total dose of opioids (in micrograms) received by the patients will be recorded at the end of the surgery. VAS pain score will be performed immediately postoperatively and at three months after the intervention. A DN4 questionnaire (neuropathic pain) will be evaluated at three months after the intervention.

Nct (2021). "Improving Sleep in Gynecologic Cancer Survivors." ClinicalTrails.gov.
	This study has two parts. In Part 1, 15 gynecologic cancer survivors will receive three candidate intervention components known to reduce sleep disturbance (i.e., sleep restriction, stimulus control, systematic light exposure) simultaneously for six weeks. Participants will then complete semi‐structured individual interviews to provide feedback about barriers to and facilitators of intervention adherence. Results of Part 1 will inform the design and delivery of the candidate components in Part 2. In Part 2, a 2^3 full factorial design will be followed to randomize 80 gynecologic cancer survivors to one of eight six‐week intervention conditions reflecting all possible combinations of the three candidate intervention components.

Nct (2021). "Individualized Response Assessment to Heated Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Ovarian, Colorectal, Appendiceal, or Peritoneal Mesothelioma Histologies." ClinicalTrails.gov.
	Background: Peritoneal carcinomatosis is uniformly fatal if untreated; improved outcomes are seen with aggressive cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). The selection of chemotherapeutic agent for HIPEC is largely based on primary tumor histology and provider preference as opposed to knowledge of the potential efficacy of a specific agent for an individual patient. HIPEC is intended to target small or microscopic residual disease following complete cytoreduction; however, the actual efficacy and additional benefit of HIPEC is in question. The SMART System provides an ideal platform upon which to perfuse small peritoneal tumor tissue implants and simulate HIPEC treatment ex vivo. Tissue response to simulated ex vivo HIPEC treatment in the SMART System could inform chemotherapeutic agent selection for subsequent cytoreduction and intra‐operative in vivo HIPEC treatments. Objective: To determine the correlation between ex vivo simulated HIPEC in the SMART System and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki‐67 Eligibility: Histologically confirmed peritoneal carcinomatosis from appendiceal, colorectal, ovarian, or peritoneal mesothelioma histologies Absence of extra‐abdominal metastatic disease Participant deemed able to undergo complete cytoreduction Age >= 18 years of age Design: This is a Phase I study of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), with randomization to one of two accepted HIPEC treatment regimens as determined by primary histology. At the time of cytoreduction, representative peritoneal tumor biopsies will be obtained before and after intra‐operative in vivo HIPEC treatment. Tumor nodules harvested before intra‐operative HIPEC will be placed in the SMART System, exposed to simulated ex vivo HIPEC treatment, and then perfused, with subsequent assessment of percent necrosis and Ki‐67. Tumor nodules harvested immediately after intra‐operative HIPEC will be placed in the SMART System and perfused, with subsequent assessment of percent necrosis and Ki‐67. The correlation of percent necrosis and Ki‐67 assessment following simulated ex vivo HIPEC and intra‐operative in vivo HIPEC will be determined.

Nct (2021). "Induction Chemotherapy Combined With Immunotherapy Followed by Concurrent Chemoradiation in Advanced Cervical Cancer." ClinicalTrails.gov.
	The main objective of this study is to determine whether neoadjuvant chemotherapy combined with slulimumab sequential concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced cervical cancer could improve progression‐free survival rates. Women in the experimental arm will receive neoadjuvant chemotherapy (cisplatin plus paclitaxel) combined with slulimumab every 21 days during 2 cycles followed by concurrent chemoradiation therapy. Women in the control arm will receive concurrent chemoradiation therapy alone. 286 patients will be recruited during 2 years, with 3 years of follow up period.

Nct (2021). "Insomnia and Mindfulness Stress Reduction Program." ClinicalTrails.gov.
	Menopause is a medical term defined as the absence of menstrual bleeding lasting more than one year in women in a certain period of life. Menopause is the longest life stage in a woman's life, in which psychological and social changes are experienced as well as physical changes and some health problems occur. The symptoms of menopause develop due to varying degrees of somatic and psychological changes that occur as a result of the gradual loss of function of the ovaries. One of the most common and disturbing symptoms of menopause is sleep problems. Sleep is accepted as one of the basic physiological needs of humans, which covers 1/3 of human life and ensures the continuity of health. In addition to productivity and efficiency, sleep positively affects cognitive functions such as memory and concentration and contributes to physical and psychological restoration. Because of these positive effects, sleep is seen as an important health variable that affects an individual's quality of life and well‐being. The need for sleep is included among the basic care problems by nursing theorists, and sleep‐related problems are included as a nursing diagnosis in the nursing literature. "Discomfort in sleep pattern", which is defined as a condition that causes discomfort in the quality and quantity of the resting pattern or affects the lifestyle, is an important nursing diagnosis that also affects the quality of life and is among the nursing diagnoses determined by NANDA (North American Nursing Diagnosis Association). In order to cope with the problems participan experience in the menopausal period, women seek various pharmacological and non‐pharmacological ways. When the studies conducted in recent years are examined, it has been determined that the commonly used complementary alternative therapies reduce the complaints experienced in menopause. One of the complementary alternative therapies is mindfulness. In the literature, it has been stated that mindfulness stress reduction program reduces menopausal symptoms. Nurses should have knowledge about menopause and coping methods in the field. Counseling the individual and the family is among the responsibilities of the nurse. Although the number of studies examining the effect of mindfulness stress reduction program and acupuncture on insomnia, which is one of the menopausal complaints, is very few in the literature. It is thought that this study, which was designed to examine the effect of mindfulness stress reduction program on insomnia and quality of life from menopausal complaints, will provide evidence and bring innovation to nursing profession practices.

Nct (2021). "Integrative Body-Mind-Spirit Group Intervention for Infertile Couples." ClinicalTrails.gov.
	Infertility is a global public health issue, affecting approximately 15% of childbearing‐aged couples around the world. It is often a challenging dyadic life experience that generates adverse impacts on the psychosocial well‐being of couples at childbearing age. Numerous psychosocial interventions have been developed for infertile women, and their efficacy and effectiveness were supported empirically. This study attempts to address the limitations incurred in existing psychosocial interventions for infertility by: (1) including infertile men and couples who have not sought fertility treatment and (2) incorporating relational outcomes within psychosocial interventions for infertile couples. This is a two‐arm, with equal randomization, parallel randomized controlled trial. It compares the efficacy of a couple‐based Integrative Body‐Mind‐Spirit (I‐BMS) group intervention to a waitlist control group in improving dyadic couple flourishing and fertility‐related quality of life among couples who are diagnosed of infertility in Hong Kong. It also aims to investigate the dyadic associations between infertile husbands' and wives' baseline primary outcomes and changes in primary outcomes following the intervention. On hundred and seventy‐eight infertile couples will be recruited through hospitals, clinics and local communities in Hong Kong. Each prospective couple will complete an online screening survey. Eligible couples will complete the baseline assessment, and then be randomized in a ratio of 1:1 into one of the two arms. Arm 1 is the couple‐based I‐BMS intervention for infertility, which consists of four 3‐hour sessions within one month. Arm 2 is the waitlist control. Randomization will be performed by a computer. All eligible couples will be contacted by a research assistant for a pre‐group interview prior to the commencement of the I‐BMS intervention. The primary outcomes are changes over the measurement points in dyadic couple flourishing and fertility quality of life. The secondary outcomes include changes over the measurement points in empathy towards partner, partnership, relationship satisfaction, anxiety, depression, infertility‐related blame, and resilience. Assessments are administered at baseline, post‐intervention, 1‐month follow‐up, and 5‐year follow‐up. Structural equation modelling will be employed to examine the efficacy of the couple‐based I‐BMS intervention based on the intention‐to‐treat principle, as well as the dyadic association between infertile husbands' and wives' primary outcomes. Eight hypotheses are generated. First, it is hypothesized that, after controlling for baseline dyadic couple flourishing, couples in the I‐BMS intervention group will report significantly higher dyadic couple flourishing than their counterparts in the waitlist control group following the intervention. Second, it is hypothesized that, after controlling for post‐intervention dyadic couple flourishing, couples in the I‐BMS intervention group will report significantly higher dyadic couple flourishing than their counterparts in the waitlist control group at one‐month follow‐up. Third, it is hypothesized that, after controlling for baseline dyadic fertility quality of life, couples in the I‐BMS intervention group will report significantly higher dyadic fertility quality of life than their counterparts in the waitlist control group following the intervention. Fourth, it is hypothesized that, after controlling for post‐intervention dyadic fertility quality of life, couples in the I‐BMS intervention group will report significantly higher dyadic fertility quality of life than their counterparts in the waitlist control group at one‐month follow‐up. Fifth, it is hypothesized that wives' baseline fertility quality of life is predicted by their own and their husbands' baseline couple flourishing. Sixth, it is hypothesized that husbands' baseline fertility quality of life is predicted by their own and their wives' baseline couple flourishing. Seventh, it is hypothes ed that wives' post‐intervention improvements in fertility quality of life is predicted by their own and their husbands' post‐intervention improvements in couple flourishing. Eighth, it is hypothesized that husbands' post‐intervention improvements in fertility quality of life is predicted by their own and their wives' post‐intervention improvements in couple flourishing.

Nct (2021). "Interest of Bilateral Basic Tongue Mucosectomy Assisted by Robot or Laser in Combination With Tonsillectomy in the Assessment of Prevalent Cervical Lymphadenopathy." ClinicalTrails.gov.
	We are proposing a randomized phase II study to assess the benefit of bilateral robot‐assisted or laser basal tongue mucosectomy in combination with tonsillectomy in the assessment of prevalent cervical lymphadenopathy

Nct (2021). "Intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy as a Method of Fertility Preservation." ClinicalTrails.gov.
	Background: The use of intra‐operative ultrasound has been widely implemented amongst other specialties. However, within gynaecological surgery, it is not as commonly recognized, despite evidence that it can be used as an adjunct to improving minimally invasive surgical techniques. This is primarily due to the improved visualization of the operative field, which can assist more technically difficult surgical procedures, thus minimizing intra‐operative complications. The application of ultrasound guidance within gynaecological procedures have included predominantly ovarian cyst aspiration, in vitro fertilization and removal or insertion of intra‐uterine devices. Although pre‐operative imaging provides procedural planning, it cannot compare to the information gained from real time imaging. For example, in previous studies, intra‐operative ultrasound detected more myomas during myomectomy than pre‐operative transvaginal imaging. Furthermore, it provides the potential to assess lesion margins, ensuring resection of pathology is complete with negligible damage to surrounding healthy tissues. This is consistent with a recent systematic review, which also demonstrated that albeit a novel technique, amongst various case series, pathology can be safely resected without incurring injury to healthy reproductive tissue. Therefore, intra‐operative ultrasound has the potential to improve surgical accuracy, reduce complications and improve patient safety. The application of intra‐operative ultrasound as an adjunct to fertility sparing surgery has not been widely researched, with only a few case series reporting surgical outcomes on patients undergoing treatment for pre‐malignant or malignant pathology. The aim of this study therefore, is to determine the efficacy of this surgical technique in the management of benign pathology, including the surgical resection of ovarian cysts. Hypothesis: Intra‐operative ultrasound will prove a significant method of fertility preservation surgery, as measured by a significantly reduced decrease in Anti‐Mullerian Hormone (AMH) and antral follicle count (AFC) at 3 and 6 months post‐operatively, when compared to the control group. Study Design: This will be a multi‐centre prospective cohort study carried out as a non‐blinded randomised controlled trial. Women will be allocated to either a control group of laparoscopic ovarian cystectomy performed without ultrasound guidance, or to the experimental ultrasound guided laparoscopic ovarian cystectomy (UGLOC) group. All surgeons operating and women recruited to the study will be aware of which group they have been allocated to from the beginning of their participation to the study. The research team aims for equal sample sizes in both groups. Recruitment: Women referred to the outpatient gynaecology clinic with a suspected ovarian cyst will be asked about their clinical history and undergo a pelvic transvaginal ultrasound scan (2D and 3D ultrasonography) as part of routine clinical care. If an ovarian cyst is seen on ultrasound, it will be assessed according to local protocols based on simple descriptors and International Ovarian Tumour Analysis (IOTA) simple rules. Depending on the severity of symptoms, nature of the cyst and fulfilment of the inclusion criteria and if the woman is suitable for surgical management, she will then be invited to participate in the study. Participants will be recruited from various general gynaecology clinics, as well as specialist clinics including: ovarian cyst clinic, the IOTA and Rapid access clinics across Imperial and University College London Hospital. Following consent of participation, the woman will be assigned to either a control or experimental group. A separate research group, not directly affiliated with the project will perform the randomisation process. The research group will print x "control group" labels and x "experimental group," in which each label is then sealed into an individual envelope. All envelopes will be numbered and issued in sequence. During the recruitment proc s, once the participant has given consent to participate in the trial, a member of the research team will select the envelope in sequence, which will then assign the participant to a group. This will prevent the person performing the randomisation from selecting another envelope if they are not happy with the group allocation. For this study, it will not be necessary to postpone diagnostic procedures or treatment, and participation will not influence normal treatment. Surgical Intervention: The same surgeons will operate on women in both the control and experimental group. This will aim to exclude bias which may otherwise attribute findings to the surgeon operating. Surgery will be performed at Imperial Healthcare NHS Trusts and at the University College London Hospitals NHS Foundation Trust by an experienced clinician. Data Collection: The research team will collect the following data: Participant demographics including age, BMI, gravida, parity and gynaecological surgical history. Pre‐operative data will include findings from the diagnostic transvaginal scan and measure of ovarian reserve: AMH and AFC. Intra‐operative data will include transvaginal findings during surgery (in the experimental group only), such as cyst location and size or any new lesions noted. Residual ovarian volume post cystectomy will also be measured intraoperatively. Histology data will include the histological diagnosis of the ovarian cyst and volume of normal ovarian tissue excised during the cystectomy measured as per margins in mm. Outcomes following surgery including duration of surgery (mins), length of hospital stay (days) and post operative complications will be recorded. Follow up: Post‐operatively, participants will return to their respective hospital gynaecology clinic responsible for the care and management of the ovarian cyst for follow up at 3 and 6 months. During the appointment a blood test will be taken to assess ovarian reserve by measuring the AMH level. The outpatient gynaecology nurse in clinic or research staff will be responsible for taking the blood sample and will only require one EDTA bottle (yellow top) to be filled (20‐40mls). The blood samples will be processed by Imperial College Healthcare Trust laboratories or University College London Hospitals NHS Foundation Trust, depending on the site taken, and will be discarded as per local protocol once the AMH has been determined. There are no specific storage or transfer requirements outside of normal practice. Therefore, samples will be 'podded' to the labs once taken in the usual way. In addition, an ultrasound will be performed during the follow up appointment by an experienced gynaecology specialist trainee or Consultant to assess the AFC and preserved ovarian volume of tissue remaining. Any incidental findings identified on ultrasound scan of gynaecological pathology, will be managed by the responsible clinician and the participants GP will be informed by letter. Follow up appointments should take approximately 20 minutes. The two blood tests and two ultrasound scans carried out during the follow up process are considered standard clinical practice, and therefore not considered additional investigations for the purpose of this research study. The majority of participants are likely to be discharged following their 2nd clinic appointment 6 months post‐ surgery, whereby no further involvement in the study is required. If a participant becomes pregnant during the follow up period, clinic appointments will be deferred to 3 and 6 months post‐partum.

Nct (2021). "Intravaginal Electrical Stimulation With Different Treatment Frequency in Women With Idiopathic Overactive Bladder." ClinicalTrails.gov.
	This study is a prospective, randomized controlled trial. The trial is held at Urogynecological Rehabilitation Unit of Physical Medicine and Rehabilitation Department between February 2021 and July 2021. The local ethics committee approve the study (E‐60116787‐020‐4274). All women are informed about the purpose and contents of the study and all women written consent to participate in the study. A random allocation sequence was generated at 1:1 ratio. By using a random number generator, women are randomized into two groups as follows: Group 1 receive BT+IVES (2 times/week), Group 2 receive BT+IVES (5 times/week). All women which are planned to treat during 20 sessions are included in this study. Bladder Training (BT) All women were informed about BT for 30 minutes in two groups. Then it was given as a written brochure to be implemented as a home program. BT, consisting of four stages, did not contain any PFM training programs. At the first stage, all of the women visited the physician who was blinded to the study groups and at the initial visit, the women were familiarized with the location of the PFM and the pelvic anatomy and pathophysiology. After that information session, squeezing the PFM was shown in practice at least once to use in the urgency suppression strategies via digital palpation technique. In the second stage, including urgency suppression strategies, it was aimed to delay urination, to inhibit detrusor contraction and to prevent urgency; by squeezing the PFM several times in a row (women were encouraged to pause/stop their work, sit down if possible, relax the entire body and squeeze PFM repeatedly), breathing deeply, giving their attention to another job for a while and self‐motivating (I can do it, I can check the urination, etc.). In the third stage, timed voiding program was started. It was carried out in 2 steps: timed voiding and increasing the time between urination considering the voiding diary. At the last stage, the women were encouraged to continue BT. By increasing their motivation that it is an effective treatment method, compliance to the treatment was increased. Group 1: IVES (2 times in a week) This group included the IVES in addition to all components of the BT. IVES was performed in lithotomy position via electrical stimulation device with a vaginal probe. IVES sessions were performed two times in a week, for 10 weeks. Every session lasted 20 minutes. The intervention comprised a 20‐sessions treatment program of ES. The stimulation parameters were frequency at 10 Hz, a 5‐10s work‐rest cycle and 100 ms pulse width. The symmetric biphasic pulse wave could be delivered over a range of 0‐100 milliamp (mA). The intensity was controlled according to patients' discomfort level feedback. Group 2: IVES (5 times in a week) This group also included the IVES in addition to all components of the BT as in Group 1. IVES performed in the same way as Group 1, except for frequency of treatment. IVES sessions were performed five times in a week, for 4 weeks. Every session lasted 20 minutes. The intervention comprised a 20‐sessions treatment program of ES. Stimulation parameters were the same as Group 1.

Nct (2021). "Intravenous Immunoglobulin and Prednisolone for RPL After ART." ClinicalTrails.gov.
	In a randomized, double‐blinded, placebo‐controlled trial, this study aims to investigate whether treatment with prednisolone and intravenous immunoglobulin (IVIg) before and in early pregnancy improves the chance of a live birth in women undergoing treatment with artificial reproductive technologies (ART) (defined as IVF or ICSI or FER treatment) after previous recurrent pregnancy loss (RPL) after ART. If an improved live birth rate can be confirmed, the treatment will be the first documented treatment supplement for women with RPL undergoing ART treatment. A treatment with such effect is highly desirable. If the treatment increases the birth rate, it will potentially also improve quality of life and reduce detrimental anxiety and stress symptoms associated with RPL and ART treatment, since the burden (including the number of treatments and the number of losses) will be reduced. Potential study participants will be identified among patients who are referred to The Center for Recurrent Pregnancy Loss of Western Denmark (in the following called The RPL Center), located at Aalborg University Hospital (AaUH) Denmark. At the first appointment at The RPL Center, a list of standard health information important for the RPL examination will be collected together with the RPL Center's standard blood sample. Treatment: The participants will be randomly allocated 1:1 to active immunomodulatory treatment versus placebo treatment (see Arms and Interventions). Study treatment starts on the patient's first day of her menstrual cycle in which her fertility clinic plan to transfer an embryo/blastocyst(s) and continue until a negative pregnancy test, the time of biochemical pregnancy loss/miscarriage or pregnancy week 8+0, whichever comes first. from first day of cycle and until embryo transfer, one tablet (5mg prednisolone or placebo) per day is taken. First infusion (IVIg or Albumin) is given within 5 workings days before and 2 working days after embryo transfer. On the day of embryo transfer, two tablet per day is taken. Approximately 14 days after ET, the patient will have a pregnancy test. If positive, the patient will have plasma‐hCG measured twice with 1‐2 days interval at her local hospital. With adequate increment of plasma‐hCG, the patient will be booked for her last 3 infusions in gestational week 5, 6, and 7, and continue tablet intake. If she is not pregnant, study medication will not continue. On the day of the first infusion treatment and again approximately four weeks later (the day of her third infusion treatment during pregnancy), a study specific blood sample will be taken for our research biobank. In participants who do not achieve pregnancy or have a miscarriage before gestational week 6 (and therefore do not come for the third infusion), we will ask these participants to come for the second blood sample too. The blood samples will be analysed by the Department of Clinical Immunology at AaUH. In addition, in a separate study performed by the same investigators, a group of 37 healthy females in reproductive age with no prior known pregnancy losses will have one blood sample collected in their luteal phase and analyzed according to the same protocol and will serve as a reference group to the two study groups. An immediate analysis of the blood sample will quantify NK‐cells, B‐cells, and T‐cell subsets by flow cytometry. Also, a TruCulture analysis for activity of leucocyte subsets will be carried out in 25 patients. The research/future biobank will store frozen serum and plasma for analysis of immune markers including smaller extracellular vesicles. If the participant is still pregnant after her last infusion of study medicine before week 8+0, she will be offered routine monitoring at The RPL Center at AaUH, at her local fertility clinic, and her local hospital. She will receive a questionnaire 2 weeks after her nuchal scan and 2 weeks after her due date for collection of data regarding her pregnancy, delivery, and perinatal outcome. Study‐relevant data will be collected from medical records, bi h records, questionnaires, and the research biobank. Adverse events will be recorded on all participants from the day of admission and until 6 months after last infusion treatment or until birth of her child if she becomes pregnant. Both adverse events in the participant and her child will be recorded. To support compliance and meticulous reporting of side effects, all participants receive a folder with a list of all known side effects to prednisolone, IVIg and albumin, a diary with boxes to tick of every day the tablet(s) is taken, and a table in which side effects can continuously be noted. According to the child, negative perinatal outcomes (e.g., low birth weight, preterm birth, stillbirth) and malformations will be recorded after birth.

Nct (2021). "Is Laparoscopic Excision for Peritoneal Endometriosis Helpful or Harmful?" ClinicalTrails.gov.
	The trial seeks to test effect of laparoscopic excision of peritoneal endometriosis on pelvic pain. Data will also be gathered on quality of life and neuropathic pain. Patients will be randomized to one of three groups: 1) laparoscopy with excision of endometrial tissue, 2) laparoscopy without excision of endometrial tissue and 3) waiting list control.

Nct (2021). "Is Preoperative Urodynamics Essential for Women With Pelvic Organ Prolapse." ClinicalTrails.gov.
	60 patients, fulfilled the selection criteria were counseled and informed about the trial protocol and a written consent according to declaration of Helsinki was signed. Participants were randomly assigned following simple randomization procedures (computerized random numbers) to group (1) or group (2). Each group consisted of 30 patients. All participants had been thoroughly evaluated by history and examination. A standardized questionnaire was obtained to evaluate the symptoms of stress urinary incontinence, urge urinary incontinence and obstructive symptoms. Clinical staging of pelvic organ prolapse by POP Q Staging. Ultrasound examination had been also carried out to rule out any pelvic pathology. Patients had completed a 3‐day bladder diary (frequency volume chart) to assist in arriving at an urodynamic diagnosis. Urinalysis was performed. Only patients allocated for group 1 were subjected to urodynamic studies before surgical intervention and then corrective procedures for POP had been done .The Urodynamic studies carried out were : uroflowmetry and cystometry. The Uroflowmetry was performed by the gravimeter method, where maximum flow rate, average flow rate, voided volume and residual urine was measured. Maximum flow rate ≤15 ml/sec, and/or residual urine of more than 50 ml or 10% of voided volume in a bladder filled with a minimum of 150 ml was taken as cut off to detect abnormal voiding. Cystometric parameters which indicated normal bladder function were first desire to void between 150 and 200 ml, capacity (taken as strong desire to void) of greater than 400 ml, detrusor pressure rise on filling of less than 15 mm H2O per 500 ml infused, absence of detrusor contractions, no leakage on coughing, no significant pain on filling and finally a detrusor pressure rises on voiding (maximum voiding pressure) of less than 50 cm H2O, with a peak flow rate of more than 15 ml/s for a voided volume over 150 ml. Urodynamic stress incontinence was diagnosed when urethral leakage was seen with increased abdominal pressure, in the absence of detrusor contractions. Detrusor over activity was diagnosed when the patient has involuntary detrusor contractions during filling with or without leakage which may be spontaneous or provoked. All participants were followed‐up with same questionnaire and clinical examination after 12 weeks post operatively.

Nct (2021). "Ketogenic Diet in PCOS With Obesity and Insulin Resistance." ClinicalTrails.gov.
	Consecutive patients coming to the Endocrinology and Diabetes Clinic of the S.Orsola hospital in Bologna with the suspicion of PCOS, during the study period, will be eligible to participate. In the screening phase, patients from the clinic conforming to the inclusion criteria will be invited to participate in the anovulation screening phase, lasting up to 8 weeks, during which measurements of LH, FSH, estradiol, progesterone and a gynecologic ultrasound will be done on 7th, 14th, 21st and 28th day of the presumed ovulatory cycle, or at any time if amenorrhea present. Consenting participants will provide written informed consent. Following the anovulation screening, the patients will be randomized in two arms of the study: 1. very low calorie ketogenic diet (VLCKD) and the 2. low calorie standard diet (LCD). The study is open label; thus, patients and investigators will not be blinded to treatment allocation due to the nature of the study intervention. The group assigned to the VLCKD will follow the VLCKD for 8 weeks, after which they will follow the LCD for the next 8 weeks. The group assigned to the LCD will follow the LCD for the entire length of the study (16 weeks.) At the start of the study, after 8 weeks and after 16 weeks, following measurements and tests will be done: 1. clinical examination with the measurement of height, body mass, circumference at the waist and hip level, arterial systolic and diastolic pressure, heart rate, Ferriman‐Gallwey and videodermoscopic evaluation of hirsutism and bioimpedance body composition measurement; 2. blood will be taken for: lipid profile, hepatic transaminases, fasting glucose, fasting insulin, HbA1c, potassium, sodium, urea, calcium, phosphorus, total proteins, albumins, total bilirubin, uric acid, complete blood count, sex hormone binding globulin (SHBG), liquid chromatography‐mass spectrometry measurement of testosterone, androstenedione, DHEA, 17OH‐progesterone, 17OH‐pregnenolone; 3. dietary interview; 4. psychological evaluation using the following questionnaires: Symptom Questionnaire, the Psychosocial index and the Psychological Well‐Being scales.

Nct (2021). "Kinesiological Taping and Aerobic Exercise in Women With Primary Dysmenorrhea." ClinicalTrails.gov.
	Dysmenorrhea is defined as the pain and discomfort of women during the menstrual period. Kinesiological taping (KT) and aerobic exercise (AE) are effective methods for dysmenorrhea. The purpose of this study is to investigate the effects of KT and AE on pain, attitude, depression, and quality of life in women with dysmenorrhoea. Forty‐five women with dysmenorrhea wıll randomly be divided into three groups as KT group (n=15), AE group (n=15) and control group (n=15). In KT Group, 6 sessions of KT will be applied, starting on the 14th day of the menstrual cycle and 2 times per week for 3 weeks until the end of the cycle. In the AE group, walking and climbing stairs will be given during the menstrual cycle, 3 days a week, 45 minutes. No application will be applied to the control group. All groups will be evaluated with Beck Depression Scale (BDS), Mcgill Pain Questionnaire (MPQ), Menstrual Attitude Scale (MAS), and Short Form‐ 36 (SF‐36) before and after the intervention.

Nct (2021). "Laparoscopic or Abdominal Radical Hysterectomy for Cervical Cancer(Stage IA1 With LVSI, IA2)." ClinicalTrails.gov.
	The purpose of this study is to compare LRH (or robotic‐assisted) and ARH in patients with cervical cancer (Stage IA1 with LVSI, IA2), by a multicenter stratified randomized controlled study, mainly including the following aspects: 1. To compare the differences in PFS and OS between patients receiving LRH and ARH. 2. To investigate whether PFS and OS in LRH can be improved by more rigorous specification of surgical details (including tumor‐free principles and standard surgical scopes). 3. To assess postoperative complications and quality of survival.

Nct (2021). "Laparoscopic or Abdominal Radical Hysterectomy for Cervical Cancer(Stage IB3,IIA2)." ClinicalTrails.gov.
	The purpose of this study is to compare LRH (or robotic‐assisted) and ARH in patients with cervical cancer (Stage IB3, IIA2), by a multicenter stratified randomized controlled study, mainly including the following aspects: 1. To compare the differences in PFS and OS between patients receiving LRH and ARH. 2. To investigate whether PFS and OS in LRH can be improved by more rigorous specification of surgical details (including tumor‐free principles and standard surgical scopes). 3. To assess postoperative complications and quality of survival.

Nct (2021). "Laser Therapy in Women With Lichenoid Disorders." ClinicalTrails.gov.
	Background: Lichenoid Disorders (LD) include VLS (Vulvar lichen sclerosus) and LP (Lichen planus). VLS and LP are chronic skin diseases that usually affect the anogenital region. Both can cause vulvar itching, burning and pain and can lead to urinary and sexual dysfunction. Current treatment options are unsatisfactory. Vulvovaginal laser therapy might be an effective treatment option. Study aim: To study the effectiveness of non‐ablative vulvovaginal laser therapy for women with lichenoid disorders. Design: Randomized double‐blinded placebo‐ controlled clinical study Study Population: Women diagnosed with LD will be recruited from a specialized University outpatient clinic. Study groups: Participants will be randomized (1:1). Intervention group: Laser therapy (2 treatments), plus ongoing therapy Control group: Sham laser therapy (2 treatments) plus ongoing therapy Sample size Total 40 patients Primary study outcome: Visual analogue scale (VAS) composite score in regard to LD Secondary study outcomes: quality of life (QoL) (Skindex questionnaire); Treatment discomfort/ pain (VAS); Patient treatment satisfaction (Questionnaire to ask for treatment satifsaction: ZUF‐8); Subjective improvement (Patient global impression of improvement‐ PGI‐I), clinical LS score, histological appearance

Nct (2021). "Laser vs Clobetasol for Lichen Sclerosus." ClinicalTrails.gov.
	Lichen sclerosus (LS) is a common autoimmune disorder of the genital skin. It affects 1/900 women with an age peak in the sixth decade of life. LS is a chronic inflammatory condition affecting the genital, perineal, and perianal areas and causes itching, burning, pain, and soreness. Histologically, LS is characterized by epidermal atrophy, hyperkeratosis, follicular plugging, degeneration of the basal layer, and subepidermal hyalinization of collagen in the papillary dermis with a lymphocytic infiltrate. Affected women typically suffer significant long‐term genital damage including scarring, fusion of the vulval labia, narrowing of the vaginal opening, dyspareunia, and burying of the clitoris. In addition, LS is associated with an increased risk of vulvar cancer. Treatment options of LS include topical steroids such as clobetasol, topical immunomodulators such as tacrolimus, and non‐ablative laser treatment. In a systematic review of the literature with 7 studies and 249 participants, clobetasol achieved improvement rates and remission rates of 70% to 89% and 20% to 35%, respectively. In comparison, non‐ablative laser treatment leads to significant improvements in vulvar itching, dryness, pain, and dyspareunia in 50% to 85% of women with remission rates of up to 80% after 14 years of follow‐up. Although both treatments are well documented and used in clinical practice, direct comparative studies assessing the efficacy of topical corticosteroids versus laser treatment in women with LS are rare. For example, in a PubMed literature search (search date 2021‐03‐14; search terms: lichen sclerosus, laser, corticosteroids, steroids, clobetasol, randomized) only one randomized trial was identified. In this study, the authors included 40 women with LS and compared 3 applications of non‐ablative laser 2 weeks apart with 4 weeks of twice daily (2 weeks), once daily (1 week), and every other day (1 week) of topical clobetasol 0.05% cream. After 3 months of treatment laser‐treated women had a significantly higher sum score (including burning, itching, and pain) measured on an 11‐step visual analogue scale (VAS). Both treatments demonstrated histological improvement with reductions of inflammatory hallmarks in skin biopsies. Given this body of evidence, more high‐quality studies are needed to define the superiority/inferiority of the different available treatment options such as non‐ablative laser and topical corticosteroids. Therefore, a prospective, randomized trial comparing non‐ablative CO2 laser treatment and topical clobetasol 0.05% will be conducted. The aim of this prospective, randomized, open‐label, comparative trial is to establish or refute the superiority of 3 courses of non‐ablative treatment by CO2 laser every 14 days compared to topical clobetasol 0.05% (daily in month 1, every other day in month 2, and 3 times/week in month 3) for 3 months. The primary endpoint of this study is a sum score including the pathognomonic symptoms of LS, namely vulvar burning, itching, and pain, each measured on an 11‐step VAS. Secondary endpoints will include the physician‐scored rate of visual improvement (measured on an 11‐item VAS), side effects, and patient‐reported outcomes such as subjective overall improvement, general satisfaction, and quality of life (measured by a validated questionnaire for vulval disorders; i.e. the VDQI (Vulval Disease Quality of Life Index).

Nct (2021). "Light Emitting Diode in the Treatment of Genitourinary Syndrome of Menopause." ClinicalTrails.gov.
	Introduction: The genitourinary menopause syndrome (MMS) affects 50% of postmenopausal women and, due to a decrease in hormone levels, triggers functional changes in the vagina and vagina, and impairment of quality of life and sexual function. Objective: To test the hypothesis that the 405 nm light emitting diode in the treatment of vulvovaginal atrophy is safe and effective, by reducing the symptomatology of the disease and histological alteration of the tissue. Methods: This is a pilot study in 10 volunteers with SGM, followed by a randomized, blinded trial in a sample of 58 individuals that will be performed at the Pelvic Floor Care Center (CAAP). Menopausal women up to 65 years of age and with clinical signs and symptoms of vulvovaginal atrophy syndrome (vaginal dryness and irritation, pruritus, pain or discomfort in intercourse, bleeding after sexual intercourse) and who voluntarily participate in the study will be included. Will be excluded from the study the patients in hormonal replacement for less than 6 months, diagnosis of vaginal infection, use of pacemaker, pregnant women, those who have performed Oophorectomy or presented ovarian cancer, difficulty understanding the proposed instruments and patients with chronic neurological degenerative diseases. Three 405 nm light emitting diode (LED) sessions will be performed, with a seven days interval between them. In the clinical trial, the study group will perform kinesiotherapy and LED. The control group will perform kinesiotherapy and the LED will be turned off. Data collection will be performed initially and after the sessions through self‐administered questionnaires containing socio‐demographic and clinical information, Medical Outcomes Study 36, Short‐Form Health Survey (SF‐36), Female Sexual Function Index (FSFI) ‐ Female Version (QS‐F), Female Genital Self‐Image Scale ‐ 7 (FGSIS‐7). At the end of treatment, the visual analog scale and Likert scale will be used to measure the individual's satisfaction. Expected results: The 405nm LED in the vaginal canal is expected to be safe and effective for SGM.

Nct (2021). "Long-term Use of Mifepristone in the Treatment of Adenomyosis." ClinicalTrails.gov.
	The design was a prospective, randomized, positive‐control, parallel‐group, multicenter clinical trial. The study included a randomized, parallel‐group treatment for 24 weeks in 140 subjects from eight hospitals in seven cities across the country who were diagnosed with Adenomyosis and associated symptoms (dysmenorrhea, with or without heavy menstrual flow) , the subjects were randomly assigned to the following two groups: 1. Study Group: mifepristone tablets, 10 mg, 1 tablet daily, taken orally (beginning on the third day of Menstruation) for 24 weeks; 2. Control Group: dafinil (Triptorelin Acetate) , 3.75 mg, first injection on the third day of menstruation, followed by intramuscular injection every 28 days for 24 weeks.

Nct (2021). "LTAP Block in Endometriosis Surgery - a Randomised Controlled Double-blind Trial." ClinicalTrails.gov.
	The LTAP‐trial is a prospective randomized controlled double‐blinded study comparing the efficacy and safety of LTAP with local wound analgesia in laparoscopic endometriosis surgery. Patients are randomized to receive LTAP with levobupivacain and wound infiltration with placebo or wound infiltration with levobupivacain and LTAP with placebo. The primary outcome is postoperative opioid consumption measured by Patient Controlled Analgesia ‐pump (PCA). Secondly, subjective postoperative pain up to 24 h postoperatively will be measured by Numeric Rating Scale (NRS). Additional outcome measures are factors related to recovery and length of stay in the hospital as well as a 6 month follow‐up survey regarding pain and general wellbeing after surgery. A total of 46 patients will be randomized in a proportion of 1:1.

Nct (2021). "Lymphadenectomy in Early Ovarian Cancer." ClinicalTrails.gov.
	OBJECTIVES: Compare the efficacy and safety in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA ‐IIA epithelial ovarian cancer, undergo completion staging surgery including systematic pelvic and para‐aortic lymphadenectomy versus comprehensive staging surgery without lymphadenectomy. OUTLINE: This is a randomized phase III multicenter study. Patients will receive comprehensive staging surgery without Lymphadenectomy or completion staging surgery including systematic pelvic and para‐aortic lymphadenectomy, and the adjuvant chemotherapy will accord to National Comprehensive Cancer Network (NCCN) guidelines. Patients are followed up every 3 months within the first 2 years, and then every 6 months. PROJECTED ACCRUAL: A total of 656 patients will be recruited for this study within 5 years.

Nct (2021). "mHealth Mindfulness Intervention for Pregnant Black and Latina Women at Risk of Postpartum Depression." ClinicalTrails.gov.
	Postpartum depression (PPD) is associated with significant health consequences for mothers and children, and the current COVID‐19 pandemic has had a major impact on the mental health of particularly vulnerable populations including pregnant Black and Latina women. There is an urgent need for evidence‐based, accessible, and scalable mental health care options for these high‐risk, vulnerable women. This study aims to: (a) compare the effectiveness of two digitally‐delivered self‐paced stress reduction programs in pregnant Black and Latina women at increased risk of PPD; and (b) examine barriers and facilitators to implementation within a large healthcare system.

Nct (2021). "Mindful Kangaroo Care: mindfulness Intervention for Mothers During Skin-to-skin Care." ClinicalTrails.gov.
	BACKGROUND Kangaroo Mother Care (KMC) was developed to complement neonatal care for premature and low birth weight infants in areas where there were fewer resources. During KMC, a baby is positioned in skin‐to‐skin contact with the mother's (or father's) chest and each session may last for 30 minutes to a few hours or longer as tolerated. A recent meta‐analysis concluded that KMC resulted in better thermal regulation, physiologic stability, enhance breastfeeding and also reduced mortality and infection. KMC has also been shown to improve mother‐infant attachment and reduced maternal stress. KMC is widely practiced across the world. Skin‐to‐Skin care has also been identified with certain challenges and concerns, especially in the immediate neonatal period. There are several instances of the sudden unexpected postnatal collapse of babies reported. In most instances, these episodes were associated with inadequate standardization in selecting mother‐baby dyads. There is a strong association with the baby's position, maternal sleep while KMC and inadequate monitoring during KMC. Maternal and neonatal fall while giving KMC has also reported as a concern especially associated with maternal sleep while providing KMC. KMC in a NICU environment has its own challenges with barriers identified in a recent systematic review including, staffing issues, inadequate training available, difficulties in transferring babies for KMC while attached to infusion pumps and ventilators, stress among caregivers and families. It has also been observed that mothers giving KMC for preterm infants in a NICU environment focus on the cardiorespiratory monitoring and its alarms instead of focusing on the baby and "being in the moment". There have also been other challenges noted with maternal sleep while providing KMC and parental distraction on hand‐held devices while providing KMC. Parents of babies admitted to the NICU undergo a lot of stress. A systematic review of the parental experience of having an infant in the NICU showed that parents experience anxiety and stress. Symptoms of acute stress disorder in 40% of mothers 7‐10 days after the birth of the premature infant has been reported in a prospective observational study conducted here at the Stollery Children Hospital, Edmonton. Another study evaluated symptoms of post‐traumatic stress disorder (PTSD) and found that 51% of mothers and 33% of fathers screened positive for PTSD. Mindfulness offers a way to focus on being in the moment and accepting the present moment in a non‐judgemental and compassionate manner. Mindfulness has been shown to reduce stress in parents of babies admitted to NICU. This pilot study is planned to explore the opportunity of teaching Mindfulness skills to mothers providing KMC and studying its effects on maternal stress and distraction. To our knowledge, there are no scientific studies that evaluated mindfulness during kangaroo care or skin‐to‐skin care. OBJECTIVE To explore the feasibility and acceptability of practicing Mindfulness while giving Kangaroo mother care ‐ "Mindful Kangaroo care" To explore potential benefits of Mindful Kangaroo care, such as stress reduction, change in mindfulness state, variation in screening for depression and anxiety and overall satisfaction with this practice MATERIALS AND METHODS This study is a non‐blinded, prospective, observational pilot randomized controlled study. Inclusion and Exclusion Criteria Postpartum mothers whose baby is receiving care at the Stollery Children Hospital NICU, Royal Alexandra site, are eligible to enter the study. Mothers would be eligible to participate a) if they speak, read and write English, b) if their baby is anticipated to require a NICU stay of at least 4 weeks following recruitment, c) if the baby's medical condition allows for skin‐to‐skin care at recruitment, d) if the mother is available to do regular kangaroo care during the next 4 weeks after recruitment and if the mother is agreeable to receive some teaching for 30‐45 minutes weekly during those four w ks. Mothers whose baby is experiencing imminent risk of death at recruitment will be excluded. Mothers who reported current mental illness issues, current or prior substance abuse/addiction will be excluded. We aim to recruit 30 participants, 15 in both groups. Procedure Once recruited, mothers will be randomized into the mindful kangaroo care intervention group or into the no intervention kangaroo care group. To ensure prior experience with skin‐to‐skin care, data collection in both groups will begin after the mother has had at least two skin‐to‐skin experiences with her baby. Interventions Mindful Kangaroo Care Group (MKCG) All research team members are mindfulness practitioners and/or coaches. Some of the researchers would instruct and support weekly, one‐on‐one, all mothers in their mindfulness practices over a period of 4 weeks. The MKCG will involve four face‐to‐face direct coaching on Mindfulness techniques at weekly intervals. The following will be the broad theme of each coaching session Week 1 ‐ On the first encounter, the mothers will learn how to practice an introductory mindfulness technique to develop the awareness of any sensations felt in the body while holding their baby. Week 2 ‐ On the second encounter, the mothers will learn how to practice a second mindfulness technique to create positive feelings in the body while holding their baby. During the third and fourth weekly encounters, the mothers will have a chance to ask their questions and explore further both mindfulness techniques as needed. Control Group (CG) Standard of care will be offered to all mothers in the control group which includes kangaroo care but does not involve any mindfulness practices. The following instruments will be given for the mothers to complete to study the feasibility, acceptability and effect on stress. Power analysis will not be done because of the pilot study nature; a goal of recruiting a convenience sample of 30 mothers is set. The 30 possible participants will be randomized in a 1:1 ratio (15 participants to each group) at the time of enrollment. Instruments ‐ General Demographics Form: A researcher created maternal demographic data form (age, educational level, number of gestations, parity, prior experience with kangaroo care with other children, history of depression/anxiety, gestational age at baby's birth, birth weight, delivery type and infant age at first skin‐to‐skin experience) to be completed by the mother at enrollment. ‐ Kangaroo care log: Document recording timing and duration of kangaroo care. Document whether or not the intervention (mindfulness) is practiced using a single‐item, 5‐point Likert scale (0%, 25%, 50%, 75% or 100% of kangaroo care"). Document how long they used their phones, talk to someone and slept off while doing KMC using the same scale. Document satisfaction with Kangaroo Care for each session using a single‐item, 5‐point Likert scale ("Very dissatisfied" to "Very satisfied") measuring mother satisfaction with kangaroo care and a space to write any comments. Log to be completed by the mother weekly throughout the study time. ‐ Mindfulness scale: Toronto Mindfulness Scale as described above to be completed by the mother once at enrollment and at the end of the four weeks. An option will be added to allow the participant to express that she does not understand the statement on the scale. ‐ Stress scale: Neonatal Unit Parental Stressor Scale as described above, to be completed by the mother once at enrollment and at the end of the four weeks. ‐ Depression and Anxiety scale: Patient Health Questionnaire 4, as described above, to be completed by the mother once at enrollment and at the end of the four weeks. ‐ Feasibility form: A researcher created a data form to evaluate the recruitment capability, the data collection procedures and outcome measures, the resources and ability to manage and implement the study and intervention, to be completed by the investigators throughout the study time. ‐ Acceptability form: A researcher created a 3‐point i ert scale ("unacceptable" to "acceptable") measuring mother acceptability to the different instruments (demographic form and the outcome scales) and acceptability to the intervention, to be completed by the mother at the end of the four weeks. Statistical analyses Descriptive statistics will be calculated to summarize sample characteristics and will be compared between groups. Appropriate statistical tests (independent and paired t‐tests, Wilcoxon signed‐rank test, Mann‐Whitney U tests and χ2 tests) will be used to examine for differences between study group demographics, for differences between groups independent study variables (parent stress score, mindfulness score), and for within‐group changes in both scores from before to after the intervention. Given our small sample size, we are primarily interested in exploring the direction of any effects. Feasibility data will be analyzed by descriptive statistics where appropriate and qualitatively where appropriate. Acceptability data will be evaluated using descriptive statistics. Possible Risks: The risk is minimal. Mindfulness practice trains the brain to develop attention skills. There might be challenges that may arise during mindfulness meditation. Those challenges are usually the same that arise during normal daily life. When they occur during mindfulness, they become opportunities to develop insight. Should a mother had an overwhelming experience, the people offering mindfulness instructions to her would be able to help her. Moreover, the social workers on our unit are trained to respond to acute distress, they are aware of this research project and are willing to support the mothers as needed. Possible Benefits: There may or may not be a direct benefit to the mothers from taking part in this study. Some people experience less stress, less anxiety, less intrusive thoughts, less confusion or less foggy mind with a mindfulness practice. Some people experience more satisfaction, more fulfilment, or they become more aware of their emotions, more aware of their thinking process, more presence in their interactions and relationships. The information that we will gather may improve the care of other mothers.

Nct (2021). "Mindful Moms: mechanisms of Mindfulness-based Cognitive Therapy During Pregnancy and Postpartum." ClinicalTrails.gov.
	Pregnancy and postpartum is a period of vulnerability for new or worsening psychiatric symptoms. Mindfulness Based Cognitive Therapy (MBCT) is an effective approach to mitigate pregnancy‐related worsening of psychological distress. However, prior research has focused predominantly on symptoms of depression and anxiety, and is it not clear how or why MBCT improves psychological health during the perinatal period. Thus, the goals of this project are to (1) examine whether MBCT improves psychological functioning among pregnant women and whether these improvements persist at three‐months postpartum, (2) examine whether improved ability to regulate emotions and behavior accounts for the beneficial effects of MBCT, and (3) determine what demographic, socioeconomic, and psychosocial factors impact treatment engagement and effectiveness.

Nct (2021). "MK-7684A With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors (MK-7684A-005) (KEYVIBE-005)." ClinicalTrails.gov.
	The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of pembrolizumab/vibostolimab co‐formulation (MK‐7684A) with or without other anticancer therapies in participants with selected advanced solid tumors. The primary hypothesis is that pembrolizumab/vibostolimab co‐formulation is superior to pembrolizumab alone in terms of objective response rate or progression‐free survival in participants with cervical cancer.

Nct (2021). "MomMoodBooster VA Program." ClinicalTrails.gov.
	The purpose of the current study is to: 1) expand the MomMoodBooster intervention to pregnant Veterans and 2) to randomize Veterans to one of two intervention conditions. Veterans may be randomized to either 1) MomMoodBooster online intervention only or 2) MomMoodBooster online intervention and phone coaching. The study will examine the incremental utility of the phone coaching component of the intervention with the ultimate goal of VA‐wide implementation. Veterans who report a history of or current mania or psychosis will be referred to mental health care locally. Patients who report elevated suicide risk will be directed to go to the nearest emergency room. The study will recruit Veterans from around the nation. Investigators expect that 20% of female Veterans may be eligible. Based on national data, approximately 152,046 female Veterans in the USA are likely to have received care at a VA facility and are within the eligible age range. Centers for Disease Control and Prevention (CDC) data indicate that birth rates per 1000 women is 12.7. As such, about 3,866 female Veterans may be eligible per year. Veterans are eligible throughout the duration of pregnancy and up to 26 weeks postpartum. Use of the medical record has proved successful in screening and enrolling postpartum Veterans nationwide. Veterans who are noted to be pregnant or postpartum in the VA medical record will be contacted to determine interest and eligibility. Data will be obtained from the Veterans Health Administration (VHA) Corporate Data Warehouse through the VA Informatics and Computing Infrastructure, which includes pregnancy and postpartum diagnoses by the International Classification of Disease Tenth Revision Clinical Modification (ICD‐9 and ICD‐10 CM) codes, VHA outpatient visit dates, community care consults and medical services, patient demographics (such as race, ethnicity, date of birth, patient mailing address, and Rural‐Urban Commuting Area Codes), and contact information. These data will be stored in a Microsoft Access database on VA servers, and the database will only be accessible to select members of the research team. The data will be imported to Access by a VA employee who does not have access to any participant data following enrollment. Demographic data are expected to be complete due to data being extracted from electronic medical records. All obstetric information will be verified in the screening process to ensure updated information is considered. Oversampling for rural Veterans will be conducted with the hopes of enrolling more rural Veterans (2:1 rural:non‐rural Veteran ratio). Veterans may also be referred through Maternity Care Coordinators (MCCs) or providers at VA medical centers. The MCCs may provide Veterans with the study's contact information or call the study team directly with the Veteran's permission. Veterans may also self‐refer to the program by calling the research team or expressing interest via the MomMoodBooster website through the Contact link. Based on VA medical records that identify a Veteran as being pregnant, Veterans will be mailed a letter detailing the study, and a return letter with prepaid envelope will be provided if the Veteran wishes to decline or express interest. If interest is expressed or if no return letter is received, a member of the research team will follow‐up with a phone call to determine interest and answer questions. The study team will wait at least 5 days before following up with a phone call to ensure that the participant received the letter. The study team will call no more than 10 times without a returned phone call. A phone number is included in the letter so that Veterans can call and indicate that the Veteran is not interested in participating. The research team member will tell them about the study prior to screening if the Veteran is interested in being screened. If interested, Veterans will be screened by phone. First, the study procedures will be reviewed orally. If a Veteran wishes to review the consent document prior to screening, the study team wil ail her a copy of the consent form and call her 7 days later to review any questions and screen her if she remains interested. Veterans will be told that participation is entirely a personal choice, and participation has no bearing on healthcare at the VA or elsewhere. If a Veteran is not eligible at first screening, at the Veteran's request, the research team can call her in the future to re‐screen, provided that the factor determining ineligibility is dynamic. The screening will include access to internet/smartphone, less than 50 years of age, the PHQ‐9 for depressive symptoms, basic demographic information, contact information, and the M.I.N.I. depression, mania, and psychosis modules. If a Veteran meets criteria (10 or more on the PHQ‐9, no history or current mania, no history or current psychosis), a research team member will review the consent document and study procedures with her by phone. If she remains interested, a consent cover letter, consent document (one to sign and one for the Veteran's records), VA form for authorization to audio tape, VA HIPAA form, sociodemographic form, and baseline questionnaires will be mailed to her. Veterans will have until 26 weeks postpartum to consider whether the potential participant want to participate, at the end of which the person will no longer be eligible. Subjects will sign the VA 10‐0493 HIPAA authorization form to give permission for access to medical records. Upon receipt of the signed forms and baseline questionnaires, forms will be reviewed by the research team. After completing the baseline assessment, the Veteran will be randomly assigned to condition ‐‐ either MMB online only or MMB + phone coaching. Veterans will then be assigned a phone coach. If a Veteran is assigned to MMB online only, the phone coach will call the Veteran for symptom monitoring during weeks 1, 3, and 5 of the intervention and administer the PHQ‐9 by phone. If assigned to the phone coaching condition, the phone will call for all six weeks of the program to discuss the online content, and the PHQ‐9 will be administered during weeks 1, 3, and 5 as well. Only members of the research team have access to study data, and files have restricted access to only the team members who require access. The baseline questionnaire includes background and demographic information, the PHQ‐9, the IDAS‐II for internalizing symptoms, the BADS for behavioral avoidance and activation in depression, the Automatic Thoughts Questionnaire (ATQ) for negative automatic thoughts, the DAS for an individual's perception of the partner relationship, the Childhood Trauma Questionnaire (CTQ) for childhood trauma history, and a screening for military sexual trauma. The program will be completed in 6‐8 weeks. The program tracks use of the program, and this information is necessary for phone coaches to know whether a Veteran has logged in and completed relevant modules. This assists in the personalization of phone coaching calls. After completion of the program, Veterans are offered the opportunity to complete two booster session modules at 14‐ and 20‐weeks after enrollment. Participants in the MMB + phone coaching condition will receive two additional calls to discuss the booster session content, and Veterans who are in the online intervention only condition will receive two calls to monitor symptoms with the PHQ‐9. At any point in the program, if a Veteran expresses suicidality on the PHQ‐9, the Columbia Suicide Severity Risk Scale will be administered by a member of the research team to determine suicide risk. If a Veteran is at high risk, the Veteran will be referred to emergency care. If the Veteran is not at high risk, recommendations will be developed with the Veteran to keep them safe and encourage connection with local providers. Phone coaches are trainees who receive training and ongoing supervision in the intervention, interviewing, women's mental health, and the research protocol. The maximum number of calls per Veteran is 6 during the MMB portion of the intervention and 2 booster call f llowing completion of MMB. Duration of the calls is approximately 15‐20 minutes. Reminders will be sent via text message about 24 hours prior to the scheduled call. Text messages will contain reminder of an appointment on [date] at [time] as well as the study phone number for reference if she has questions. Reminders to log into the program may occur via MyHealthEVet or by phone call. Calls will be audio recorded and saved on the University's secure data drive. The calls will be accessible by the research team. Recorded calls will be used for supervisory and training purposes, as well as coding of fidelity and competency. After completion of the intervention, a follow‐up survey will be mailed to the Veteran for completion at 3‐ and 6‐months following enrollment. The follow‐up questionnaires include PHQ‐9, IDAS, BADS, ATQ, PSOC, DAS‐8, and the Program Evaluation Questionnaire. If a Veteran prefers, the questionnaires can be completed by phone with a research team member. All interviews or coaching calls will be audiotaped to ensure fidelity. Veterans who report depressive symptoms in the mild or higher range (10 or more on PHQ‐9) at follow‐up will be referred to closest local VA for services. Statistical analyses will compare differences between conditions over time using longitudinal modeling. The model will include condition (MMB, MMB + phone coach). Randomization will be stratified by pregnancy status (pregnant, postpartum).

Nct (2021). "Neonatal Sleep Intervention to Improve Postpartum Hypertension." ClinicalTrails.gov.
	The investigators are conducting a single center, randomized controlled trial testing the impact of a neonatal sleep intervention, the SNOO, on reducing maternal blood pressure (BP) in the postpartum period in women with hypertensive disorders of pregnancy. The SNOO is a responsive bassinet designed to automatically calm and consolidate infants by responding to their cries. Use of the SNOO has been demonstrated to improve infant sleep by 1‐2 hours nightly, thus increasing maternal sleep time. The investigators plan for 100 women with pregnancies complicated by gestational hypertension or pre‐eclampsia to be randomized 1:1 to either receive and use the SNOO responsive bassinet for their infants, or to receive the usual care of safe sleep education. Women will be followed longitudinally through 6 months postpartum with serial BPs, weights, mood assessments, and subjective and objective sleep assessments. The investigators hypothesize that for women with pregnancies complicated by gestational hypertension or preeclampsia, that poor maternal sleep quality contributes to increased BP in the postpartum period. The investigators further propose that compared to usual care (safe sleep education), an intervention targeted to improve neonatal sleep (the SNOO), and thus maternal sleep, will improve postpartum BP for these women.

Nct (2021). "A Novel Medical System for Quantitative Diagnosis and Personalized Precision Botulinum Neurotoxin Injection in Chronic Pelvic Pain Management." ClinicalTrails.gov.
	The management of pelvic floor overactivity (PFOA) using focal BoNT injection has been gaining clinical interest. Evidence has shown that BoNT injections to the levator ani in patients with CPP generated a greater than 50% improvement in symptoms at least 72% of the time, suggesting a promising efficacy of BoNT therapy. The current clinical standard for BoNT injection employs a fixed injection template or the manual palpation of a contracted muscle, followed by an injection towards the palpating finger. As such, the injection is highly subjective, operator‐dependent, variable, and not tailored to individual patients, which may lead to inconsistent outcomes. Trigger point targeted injections have been practiced for many years worldwide, yet a recent randomized controlled trial reported no significant difference in outcome between trigger point targeted BoNT injections versus a saline placebo. Furthermore, it has also been reported that neuromuscular junction (NMJ) and trigger points are distributed in well‐defined separate areas with a distance of approximately 10 mm apart. It has also been shown that BoNT injections made 10 mm away from the NMJ can reduce the efficacy of BoNT by 46%. Therefore, injections targeted at the trigger point may, in turn, compromise therapeutic efficacy. The rationale of this study is that BoNT acts at the NMJ, where the neuromuscular junctions are densely located. By specifying the muscle(s) responsible for the pelvic floor overactivity, and the offending NMJ using high density surface electromyography (HD‐sEMG), BoNT can be injected with greater accuracy and objectivity to optimize treatment efficacy. The investigators aim to test the hypothesis that interstitial cystitis patients in the guided injection arm will demonstrate lower hypertonic metrics and improved quality of life. The purpose of this study is to provide preliminary evidence supporting the use of HD‐sEMG and NMJ mapping to guide BoNT efficacy.

Nct (2021). "Online LTP+CaCBT for Treating Depression in British Mothers of African/Caribbean Heritage." ClinicalTrails.gov.
	Participants who scored 5 or above on Patient Health Questionnaire (PHQ‐9) will be would be recruited and randomly assigned into one of two groups (experimental or controlled). Experimental groups will receive the online LTP+CaCBT treatment ‐ the intervention will consist of a total of 12 group training sessions (approx. 60 minutes each). The controlled groups will receive 'placebo effects' in the form of psychoeducation involving basic discussions around mother‐child relationships, childcare, child nursing related activities and general maternal discussions. Each of the two groups (both experimental and controlled) will be comprised of approximately 10 mother‐child pairs per sub‐group.

Nct (2021). "Online Peer-Delivered 1-Day CBT Workshops for PPD." ClinicalTrails.gov.
	The COVID‐19 pandemic has further exposed vulnerabilities in social and economic systems that lead to inequalities for mothers with mental health problems and their children, worsening unintended systematic biases that exist within the healthcare system. Women with postpartum depression (PPD) are experiencing substantial worry (1), isolation, loneliness, and insomnia (2), all of which have increased levels of PPD(3,4). Mothers now have more responsibilities than ever before, providing care to their infants and toddlers, educating their older children, managing households, and supporting their partners. They are also profoundly worried about job losses, reduced income, and food insecurity (5), all of which have disrupted family routines and increased levels of partner conflict and rates of intimate partner violence.(6) Postpartum depression (PPD) typically affects up to 1 in 5 women (7‐9) and increases the risk of later depressive episodes (10), parenting problems (11), poor mother‐infant attachment (12), and emotional, behavioural, and school problems in offspring (13,14). A single case of PPD has been estimated to cost as much as $150,000 over the lifespan (15), or $57 billion for each annual cohort of Canadian births. Even under ideal conditions, the healthcare system is poorly equipped to provide care for problems requiring urgent psychotherapy like PPD (e.g., just 1 in 10 women with PPD receive evidence‐based care) (16). Barriers include women's preference for psychotherapy over medication, a lack of time, and a reluctance to travel to regular appointments (17,18). During the pandemic, the healthcare system has become even less able to help these women as public health units that previously supported the mental health of mothers have shifted their priorities to direct COVID response. Moreover, social distancing recommendations aimed at reducing COVID‐19 risk have inadvertently increased psychological distress (19) and decreased access to resources that protect against PPD including social and practical support from family, friends, and professionals. Peer administered interventions (PAIs ‐ those delivered by recovered former patients) are increasingly recognized as potentially effective alternatives to traditional mental health care services (21). Such treatments capitalize on the fact that in the case of psychotherapy, it is not clear that the level of training predicts treatment quality or outcome (22,23) for patients. Depression is an appropriate target for PAIs because it is relatively common, there is substantial unmet treatment need, and recovery rates are high, suggesting that peers will be widely available (21). The few studies that have examined the impact of PAIs for depression suggest they can be effective in both the short and long term but are most effective if: a) they are delivered by peers alone, and b) structured and based on evidence‐based treatments (rather than providing non‐specific support) (21). In the context of the COVID‐19 pandemic peer‐delivered interventions are particularly appealing, considering redeployment and re‐prioritizing of healthcare providers and services to focus on responding to the pandemic. Only interventions that are considered safe and that can be rapidly upscaled can have an impact on PPD at the population level (24). Ideal large‐scale interventions for PPD during the COVID‐19 pandemic are not only safe (i.e., delivered online), but brief, utilize the treatments most preferred by women (i.e., non‐pharmacological), reduce barriers to accessibility (i.e., self‐referred), provide skills that can be used over the long‐term, and delivered in large groups to increase social support. At present time, no interventions exist that meet all of these criteria. Research Questions Primary Research Question: Can Online 1‐Day CBT‐Based Workshops for PPD delivered by trained lay peers added to care as usual during the COVID‐19 pandemic improve PPD more than usual care alone? Secondary Research Question: Are the workshops cost‐effective? Terti y Research Question: Can these workshops reduce the impact of the common comorbidities and complications of PPD (anxiety, partner relationship discord, social support, infant temperament, parenting stress, and poorer mother‐infant attachment)? Design A parallel group RCT with experimental (immediate workshop) and waitlist control (treatment 12 weeks later) groups will address our objectives. All participants will be asked to complete study questionnaires at baseline (T1, 3 weeks before the intervention/first workshop) and 12 weeks later (T2, just prior to the waitlist control/second workshop). Peers delivering groups will be randomly assigned to workshops and not notified of group status. Intervention: The experimental (immediate workshop) group will receive the online workshop at baseline (T1), and the control (waitlist) group will receive the intervention twelve weeks later. Both groups can also receive care as usual from their healthcare providers. The online workshop was developed by the NPI, Ryan Van Lieshout (a perinatal psychiatrist who has developed and tested effective brief group CBT for PPD interventions), Peter Bieling (author of the world's leading group CBT manual), and June Brown (developer of 1‐Day CBT‐Based workshops for depression in the UK). It is a day‐long intervention delivered in 4 modules. Each participant is given a professionally designed manual (Attached) to facilitate learning. Weekly reminder emails are sent for 8 weeks after workshop completion to encourage practice. The investigators also provide a list of PPD resources and a copy of the Canadian Practice Guidelines for the Treatment of PPD (written by NPI). Lay peers who have recovered from PPD will be recruited (n=5) to be trained to deliver the workshops. The investigators will utilize the CBT training program and screening and safety protocols (e.g., handling suicidality, child safety issues) developed in the context of a previous study where a psychologist and psychotherapist delivered the 1‐Day CBT workshops. Given the situation with COVID‐19, the investigators will run the CBT workshops virtually via ZOOM. Randomization: Women will undergo block randomization to the experimental or waitlist control group using permuted block sizes of 4, 6, and 8. The randomization scheme will be generated in the statistical computing program R. The randomization of participants will be delivered to the research coordinator via the online REDCap (Research Electronic Data Capture) system. The investigators will track reasons for loss to follow‐up. Recruitment: The investigators will recruit participants via social and online media, our public health and community partners, midwifery groups, and obstetrical and family practices.

Nct (2021). "Online Peer-Delivered Group CBT for PPD." ClinicalTrails.gov.
	Mothers and birthing parents (hereafter referred to as mothers) who meet the eligibility criteria for the study (18+ years of age, with a baby under 12 months of age at recruitment, Edinburgh Postnatal Depression Scale (EPDS) score of 10 ‐ 22 and living in Ontario are screened using the Mini International Neuropsychiatric Interview (MINI). Mothers free of bipolar, psychotic or current substance use disorders and borderline personality disorder are randomized 1:1 to the intervention (online 9 week peer‐delivered CBT program) or control group (treatment as usual, TAU) after providing informed consent. Participants in the Intervention Group receive a 9 week on‐line CBT group (2 hrs weekly) delivered by Peer facilitators who have recovered from Postpartum Depression (PPD) and have been trained to deliver CBT. Participants may also continue to receive treatment as usual (medication, psychotherapy), or typical care, for new mothers from any source (healthcare providers, etc). Participants in the Control Group do not receive the CBT group and are given a list of resources for mental health and postpartum depression supports and are also encouraged to seek treatment as usual or typical care for new mothers from any source. Participants will also receive follow up emails monthly with information about when to seek emergency treatment (if symptoms worsen, experience thoughts of self‐harm or harm to the participant's baby). All participants will receive personalized emails with links to participant's online questionnaires through REDCap at 3 time points (recruitment, nine weeks later and 6 months later). Participants in the intervention group will also complete questionnaires at one time point during the intervention and a satisfaction survey at end of intervention. The data from both groups will be examined to determine treatment effects and durability, respectively. Peer facilitator fidelity to the CBT Model will be assessed using measures of adherence and competence and independently assessed by two raters.

Nct (2021). "Online PHN CBT for PPD." ClinicalTrails.gov.
	A prospective, 1‐site, parallel group, RCT (1:1 ratio) in which outcome assessors and data analysts will be blinded to maternal treatment will be used to compare online PHN‐delivered group CBT for PPD to postnatal care as usual. The primary objective of this study is to determine if online group CBT for PPD delivered by public health nurses is superior to postnatal care as usual in: a) acutely treating PPD, b) reducing relapse and recurrence, c) improving common comorbidities and complications of PPD including anxiety and the mother‐infant relationship, and d) to determine if this treatment is cost‐effective. Women in the treatment group will participate in a 9‐week group CBT intervention for PPD delivered via Zoom by two public health nurses. It consists of 9 weekly 2‐hour sessions where core CBT skills are learned and practiced, and a new psychoeducational topic is introduced and discussed by women each week.

Nct (2021). "Opening the Conversation Study." ClinicalTrails.gov.
	The specific aims of the study are: Aim 1 (Phase I). Systematically adapt an empirically supported couple‐based skills training intervention to help young breast and gynecologic cancer (BGC) survivors and their partners jointly manage the reproductive and sexual health consequences of cancer. Aim 2 (Phase II ‐ Quantitative). Evaluate the efficacy of the intervention and hypothesized mediators by conducting a randomized trial. We will evaluate the efficacy of the newly adapted intervention, Opening the Conversation (OC), on survivors' and their partners' reproductive and sexual distress as well as the relationship, sexual, and psychosocial health outcomes. We will determine whether dyadic coping and communication mediate intervention effects on survivors' and partners' reproductive and sexual distress. Aim 3 (Phase II ‐ Qualitative). Evaluate couples' experiences within and across conditions to gain in‐depth knowledge of intervention components that influence hypothesized mediators and outcomes.

Nct (2021). "Opioid Based Analgesia vs Non-opioid Analgesia for Oocyte Retrieval Procedure." ClinicalTrails.gov.
	Study Overview The investigators propose a single‐center randomized single‐blinded clinical trial in which healthy women undergoing oocyte retrieval procedures under general anesthesia will be randomized to receive either 1.5mcg/kg fentanyl or IV acetaminophen as part of multimodal analgesia. The investigators will evaluate the effects of an opioid‐free anesthesia on pain scores, analgesic medication consumption during the initial two postoperative hours, and time to discharge from PACU, compared to an opioid‐containing anesthesia.The investigators will also compare the prevalence of opioid‐related sedation side effect between opioid‐free anesthesia and opioid‐containing anesthesia. Setting and Population Inclusion Criteria 1. Written informed consent 2. 18‐45 years old 3. American Society of Anesthesiologists (ASA) physical status 1‐2 4. Undergoing oocyte retrieval procedures 5. Planned number of oocytes to be retrieved <15 Exclusion Criteria 1. Known allergy to fentanyl, acetaminophen, dipyrone, lidocaine, propofol or NSAIDs. 2. Endometriosis 3. Diagnosis of chronic pain 4. Opioid dependency, defined by consumption of oral morphine equivalent of greater than or equal to 60mg a day for 7 days or longer, for any time period. 5. Weight < 50 kg 6. Cannabis use 7. Major psychiatric disorder ‐ Schizophrenia, bipolar disorder, major depression. 8. Epilepsy disorder under anti‐convulsant therapy. 9. Renal insufficiency, defined as creatinine clearance <60 ml/hr 10. Hepatic disease Withdrawal Criteria 1. Patients are free to withdraw from the study at any time, for any reason. 2. Patients may be withdrawn from the study by a member of the study team or the clinical team, if seems appropriate for patient's safety or well‐being. Examples of such events include (but are not limited) to: an allergic reaction, analgesic failure per acute pain service judgement and significant patient discomfort. 3. Reason for exclusion will be documented, and patients will be asked to continue follow‐up according to the intention‐to‐treat principle Protocol The investigators propose a randomized, single‐blinded single‐center clinical trial. After confirming eligibility, patients will be approached before the procedure for possible enrollment in the study. After thorough explanation, written informed consent will be obtained. Patients will be randomized in a 1:1 ratio by a web‐based software to receive either: 1. Opioid‐free anesthesia, including 1. IV propofol 1‐1.5 mg/kg 2. IV acetaminophen 1000mg 3. IV dipyrone 1000mg 4. IV lidocaine 1mg/kg 5. IV dexacort 4mg 6. PR diclofenac 50 mg 2. Opioid‐supplemented anesthesia, including 1. IV propofol 1‐1.5 mg/kg 2. IV fentanyl 1.5 mcg/kg 3. IV dipyrone 1000mg 4. IV lidocaine 1mg/kg 5. IV dexacort 4mg 6. PR diclofenac 50 mg The anesthesiologist performing the procedure will not be blinded to group allocation, but other research team members and caregivers who evaluate the patients after the procedure will be. General anesthesia will be induced according to the group allocation as mentioned above. Anesthesia maintenance will be achieved with 50% N2O via a face‐mask, and additional doses of 10‐20 mg of propofol as needed. Ketamine will not be allowed. Postoperatively, intravenous tramadol 100 mg will be ordered for breakthrough pain as well as intravenous ondansetron 4mg and metoclopramide 10mg for nausea and vomiting. Patients will be followed until home discharge. The rest of postoperative care will be conducted according to standard departmental procedures by nurses and physicians. Measurements ‐ Patient characteristics and demographic data including age, weight, body mass index (BMI), tobacco use, prior IVF treatment, history of pain after previous IVF, chronic pain, chronic medication use, and American Society of Anesthesiologists (ASA) physical status will be obtained from the medical record and patient interview. ‐ Postoperative pain scores will be documented on an 11‐point Numerical Rating Scale (NRS) from 0 (no pain) to 10 (worst pain imagin le) at least once every 30 minutes for the initial two postoperative hours. ‐ Opioid‐induced sedation will be captured through the Passero opioid‐induced sedation scale (Appendix A) 20 minutes after patient admission to the recovery room. ‐ Patient satisfaction with the anesthesia will be assessed using Likert scale from 1 to 5 grading "how satisfied are the participant with the pain management they received today?" ‐ Time of discharge will be captured from the patient's electronic medical record and/or from patient interview. Sample Size Considerations To test a unilateral non‐inferiority hypothesis, assuming a 2.5% significance level, power of 80%, standard deviation of 2 points, a non‐inferiority delta of no more than 1.5 points in the 11‐point NRS pain scale between the two groups, and assumed pooled variance of 6, we will need a sample size of 42 patients in each group. Accounting for a predicted loss to follow‐up of up to 20% of patients, we aim to recruit 100 patients.

Nct (2021). "Optimal Duration of Post-Operative Activity Restriction After Midurethral Sling Procedures." ClinicalTrails.gov.
	This is a blinded, randomized controlled trial. Patients undergoing midurethral sling placement for stress urinary incontinence will be asked to participate in the study. If eligible and willing to participate, patients will be randomized to a "3 weeks post‐operative restriction" or "6‐week post‐operative restriction" of activities group. Currently, pelvic surgeons' recommendations for activity and lifting restrictions during post‐operative period vary widely from 1 to 50 pounds (10). Given variation in literature and reasonable expectations for lifting restrictions, 20‐pound lifting restriction was considered to be a reasonable and attainable expectation from patients. Both groups will be given an identical set of postoperative instructions which include refrainment from lifting anything over 20 pounds, avoid strenuous exercise, running, or perform high‐impact aerobic activities during the restricted activity period. Depending on their random allocation, patients will follow these instructions either for 3 or 6 postoperative weeks. The activities which all patients will be allowed to do during their postoperative recovery include walking, using stairs and showering in both groups. All patient will be asked to refrain from sexual intercourse for 6 weeks consistent with current routine post op recommendations (6). Other than the time of activity restriction post op (heavy lifting, strenuous exercise, running, high impact exercise), patients will receive identical postoperative instructions otherwise.

Nct (2021). "Oral Akynzeo® vs Standard of Care in Preventing CINV in High-risk MEC Patients (MyRisk)." ClinicalTrails.gov.
	Antiemetic guideline recommendations are based on the emetogenic potential of chemotherapy and involve 4 levels of classification of intravenous chemotherapy agents, i.e., high, moderate, low and minimal; these have been accepted by major organisations. Moderate emetogenic chemotherapy (MEC) results in acute vomiting in 30% to 90% of cancer patients in the absence of antiemetic therapy. In addition to the chemotherapy type, several patient‐related risk factors and clinical characteristics can increase CINV risk. These can include use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, no complete CINV response in an earlier cycle, history of nausea/vomiting, (trait) anxiety, fatigue experience, and expectations of nausea/vomiting. Other studies have largely confirmed some of the key risk factors for CINV (history of vomiting during pregnancy, history of motion sickness, age, gender) and added other factors such as (chronic) alcohol consumption, body surface area, fewer hours slept the night prior to infusion, or advanced stage cancer. Currently, there is a limited consensus surrounding the most relevant patient risk factors that may predict CINV risk. Based on a recent study by Dranitsaris et al. eight predictive factors have been identified, and an algorithm has been developed to combine these patient‐related risk factors into the optimal treatment of prophylactic antiemetics. These include: 1. nausea and/or vomiting in the prior cycle of chemotherapy 2. use of non‐prescribed antiemetics at home in the prior cycle of chemotherapy 3. platinum or anthracycline‐based chemotherapy 4. age < 60 years 5. expectations for (anticipating) nausea and/or vomiting 6. <7 h of sleep the night before chemotherapy 7. history of morning sickness during previous pregnancy 8. cycle of chemotherapy (A negative association between risk and number of cycles was identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual decline and plateau from cycle 3 onward). Akynzeo®, an oral combination of the neurokinin 1 receptor antagonists (NK1 RA), netupitant and the 5‐hydroxytryptamine (HT3) receptor antagonists (5‐HT3 RA), palonosetron, is recommended by guidelines for the prevention of CINV. Akynzeo® has been evaluated in a multicentre, randomised, double‐blind, double‐dummy phase II clinical trial at various dose ranges among 694 cisplatin‐treated cancer patients from 44 sites (two countries); each NEPA (netupitant‐palonosetron) dose significantly improves CINV prevention in cancer patients. Similar results were obtained in another international, randomised, double‐blind and parallel group phase III clinical trial; NEPA prevented CINV in patients receiving MEC. The current study primarily aimed to evaluate whether Akynzeo® leads to a higher response rate compared with standard care in MEC regimen‐treated patients who are identified to be at high risk based on the algorithm.

Nct (2021). "Oral Contraceptives for Treating Premenstrual Dysphoric Disorder in Bipolar Disorder." ClinicalTrails.gov.
	This study is a pilot, randomized, placebo‐controlled trial evaluating the treatment of Premenstrual Dysphoric Disorder comorbid with Bipolar Disorder using combined oral contraceptives. Lay Summary: This study is being done with the hope of finding a safe and effective treatment for individuals who experience both bipolar disorder and severe premenstrual symptoms. As part of this clinical trial, participants will receive either a combined oral contraceptive (i.e. oral birth control pills) as a treatment for severe premenstrual symptoms or a placebo (a pill without any active components ‐ similar to a sugar pill). People that are enrolled in this study will either receive the treatment or the placebo for a period of 90 days. During this time, people that are participating in the study will fill out some questionnaires, and their mental and physical health will be monitored by the study physicians. One of the goals of this study is to also understand whether it is feasible (practical) to do a larger clinical trial using this treatment in this group of people.

Nct (2021). "Oral Progesterone for Prevention of Miscarriage in Threatened Abortion." ClinicalTrails.gov.
	This study evaluates the effectiveness of oral dydrogesterone in preventing miscarriage in threatened abortion. Half of participants will receive oral dydrogesterone, while the other half will receive oral placebo.

Nct (2021). "Overactive Bladder Telemedicine Non-inferiority Trial." ClinicalTrails.gov.
	This is a single‐center, prospective randomized controlled trial. The study population will consist of two primary cohorts stratified based on the method of follow‐up, either traditional in‐person clinic visit or telemedicine appointment. The primary outcome will be satisfaction with OAB treatment. Secondary endpoints include rate of progression to third line therapies, changes in OAB symptom scores, safety, and cost. This non‐inferiority trial is designed to provide an alternative option for care delivery that may result in improved patient satisfaction and compliance, and decreased cost, time, and travel burden for patients.

Nct (2021). "Pain After Insufflation for Robotic Sacrocolpopexy (PAIRS) Trial." ClinicalTrails.gov.
	This is a prospective single‐blind randomized controlled trial of adult women undergoing robotic‐assisted sacrocolpopexy for pelvic organ prolapse. Each surgery will be performed by a board‐certified Female Pelvic Medicine & Reconstructive Surgery (FPMRS) surgeon with a standard technique other than pneumoperitoneum level. A sacrocolpopexy for apical prolapse may be performed at the same time as a hysterectomy and other clinically indicated procedures if desired by the patient and as part of the standard of care. Patients will be stratified by hysterectomy prior to randomization. Postoperatively, patients will be evaluated with a Visual Analogue Scale (VAS) as well as prescribed narcotic analgesic use and followed up to 2 weeks.

Nct (2021). "Para-aortic Prophylactic Irradiation for Locally Advanced Cervical Cancer." ClinicalTrails.gov.
	This clinical trial enrolled participants with locally advanced cervical cancer with positive pelvic lymph nodes below the common iliac region diagnosed by Positron emission tomography‐computed tomography(PET‐CT). Participants should be able to receive concurrent cisplatin chemotherapy. No anti‐tumor treatment was given before randomization. Participants will be randomly assigned to two groups. The study group will receive radiotherapy of pelvic and para‐aorta, concurrent chemotherapy and brachytherapy, and the control group will receive pelvic radiotherapy, concurrent chemotherapy and brachytherapy.

Nct (2021). "Patient Educational Video for Pelvic Organ Prolapse." ClinicalTrails.gov.
	This is a randomized controlled trial. Participants will be randomized either to watch a pre‐visit educational video on pelvic organ prolapse (POP) in addition to routine physician counseling (intervention group) or routine physician counseling alone (control group). The counseling physician will be blinded. All participants will complete a pre‐visit survey that includes the Prolapse and Incontinence Knowledge ‐ POP (PIKQ‐POP) and a demographics questionnaire. The PIKQ‐POP has been validated to assess for patient knowledge of POP. Those randomized to the intervention group will take a brief survey after watching the video asking if they had any technical issues with the video and confirming they watched the video. At the end of all initial clinic visits, participants will complete a post‐visit survey that includes the validated Satisfaction with Decision Scale for Pelvic Floor Disorders (SDS‐PFD) to assess the primary outcome of change in patient decision satisfaction. The SDS is designed to assess satisfaction with a treatment decision. The SDS was modified into the SDS‐PFD to be specific for women making decisions regarding surgical treatment for pelvic floor disorders. To assess the secondary outcomes of change in decision conflict and POP knowledge, the post‐visit survey will also include a validated Decision Conflict Scale (DCS) and the PIKQ‐POP. The DCS was developed to evaluate the effect of health care decision aids and decision‐supporting interventions on decision uncertainty. The physician will also complete a counseling survey at the end of the visit to assess their perception of patient comprehension and their ease of counseling. After undergoing their chosen management option, participants will also complete a post‐management survey in follow up which will include the SDS‐PFD and PIKQ‐POP.

Nct (2021). "Patient Satisfaction With Virtual Visits." ClinicalTrails.gov.
	This is a two arm, randomized non‐inferiority clinical trial that will take place within the Minimally Invasive Gynecologic Surgery division in the Women's Health Institute of the Cleveland Clinic, Cleveland, OH. Population ‐ The Investigators will recruit patients undergoing benign minimally invasive hysterectomy (laparoscopic, robotic, and vaginal). Inclusion criteria include patients >18 years of age who are able to provide informed consent without assistance, speak English, and who have access to a phone or device equipped for virtual visits. Patients will be excluded if the staff surgeon determines they are inappropriate for virtual follow‐up, if there is suspicion of malignancy, if they are unable to provide consent, or if they do not have access to technology that enables virtual visits. Recruitment ‐ Enrolled participants will be randomized to either a two‐week virtual postoperative visit with a certified nurse practitioner (CNP) or a two‐week in‐office postoperative visit with a certified nurse practitioner (CNP) in a 1:1 allocation ratio. Block randomizations with block size of 4 will be assigned to nurse providers independently. Randomization schedules will be implemented by Redcap. Data collection ‐ The primary outcome of this study is patient satisfaction, as measured by the Press Ganey Medical Practice Survey and Medical Practice Telemedicine Survey. These questionnaires are currently sent to all patients by the Office of Patient Experience at our institution four days after their postoperative appointment. The investigators will provide verbal reminders about study participation and survey administration at the visit. Survey data will be obtained through the Office of Patient Experience and imported into RedCap. The secondary outcome is a new diagnosis of a postoperative complication requiring medical treatment (e.g. calling in of a prescription), an office visit with a CNP or MIGS surgeon, or an urgent care or ER visit. Complications include infection (urinary, pulmonary, wound, pelvic abscess, and bloodstream); thromboembolic events; bleeding; and issues with wound healing, such as dehiscence. Calvien‐Dindo classification system for postoperative complications will be used. The Investigators will also look at no‐show rates, visit times, and travel distance. The investigators will collect basic demographic information from the EMR, including age, BMI, parity, and prior surgical history. Surgical indication, procedure performed, length of hospital stay, and perioperative outcomes (reoperation, readmission, unscheduled office or virtual visits (i.e. earlier than the scheduled 2 week visit), ED/urgent care visits, infection rates) will also be obtained. No‐show rates will be obtained through the EMR. The investigators will also note if a planned virtual visit is unable to be completed due to technical difficulties, or is converted to a telephone visit. Travel distance from home to clinic site will be calculated using average travel time with minimal traffic based on participant's zip code using Google Maps. The investigators will collect the reason for ineligibility for all patients deemed such by staff surgeons. All participants will be assigned a study number to facilitate de‐identification of data. Data will be compiled in RedCap and securely stored on an encrypted server. Statistical analysis Power Calculation: The Investigators hypothesized that patient satisfaction would be non‐inferior for patients randomized to the postoperative virtual visit compared to those randomized to in‐person virtual visit. Sample size of 70 patients in each arm is needed to achieve 90% power to detect a non‐inferiority margin of ‐0.20. Allowing for a dropout rate of 20%, 88 patients will be recruited in each arm. Analysis plan: For the primary outcome, the Farrington‐Manning score test for non‐inferiority will be performed, for both intention‐to‐treat and per‐protocol analyses. Approximately normally‐distributed continuous measures will be summarized using means and standard eviations and will be compared using two‐sample t‐tests. Continuous measures that show departure from normality and ordinal measures will be summarized using medians and quartiles and will be compared using Wilcoxon rank sum tests. Categorical factors will be summarized using frequencies and percentages and will be compared using Pearson's chi‐square tests or Fisher's exact tests. All analyses will be done using SAS (version 9.4, The SAS Institute, Cary, NC) and a p < 0.05 will be considered statistically significant. Study Timeline: The MIGS division performs at least 20‐30 hysterectomies per month. The Investigators estimate to achieve our target recruitment in 7‐8 months.

Nct (2021). "Peer Administered Online CBT for PPD." ClinicalTrails.gov.
	Postpartum depression (PPD) affects up to 20% of women and has profound effects on mothers and their infants. Indeed, the cost of one case of PPD is estimated to exceed $150,000. Unfortunately, fewer than 15% of women with PPD receive evidence‐based care and this is at least partly due to difficulties accessing treatment, particularly those that are most preferred (e.g., psychotherapy). Clinical practice guidelines recommend that the majority of women with PPD receive psychotherapy (e.g., cognitive behavioural therapy (CBT)) as a 1st‐line treatment and that screening only occur in settings where CBT is readily available. In order to increase access to treatment, screening efforts have been undertaken by public health units across Canada. This is despite recommendations that this only be conducted in the setting of timely access to evidence‐based psychotherapies (e.g., CBT). The purpose of this study is to apply task shifting to the treatment of PPD by determining if women with a past history of PPD (i.e., lay peers) living in the community can be trained to deliver effective group CBT to women with current PPD. A group CBT intervention for PPD has been developed and validated as well as a training program that pilot data suggests is capable of successfully training public health nurses with little background psychiatric training. This intervention is brief, effective, and generalizable to women with PPD in the community. Peer administered interventions (PAIs), those delivered by recovered former patients are increasingly recognized as potentially effective alternatives to traditional mental health care services. In addition, psychotherapy delivered online has been recognized as a delivery method that results in successful expression and interpretation of emotions, decreased inhibition and reluctance to disclose personal information and a strong therapeutic alliance between patients and providers. Online psychotherapy also has satisfaction ratings that are comparable to traditional in‐person psychotherapy. Eight lay peers will be trained to deliver our 9‐week group CBT treatment. 174 women will be recruited and using a randomized controlled trial design (with wait‐list controls), it will be determined if lay peers can deliver effective group CBT for PPD. If peers can be trained to provide effective CBT online, more women would receive treatment and the burden of PPD on women, families, and the healthcare system would be significantly reduced. Providing women with PPD with CBT skills at this crucial stage in life also has the capacity to prevent future depressive relapse with significant benefits for patients, families, employers, and the healthcare system.

Nct (2021). "Pelvic Floor Disorder Assessment of Knowledge and Symptoms: an Educational Model in Spanish-Speaking Women." ClinicalTrails.gov.
	Purpose: The purpose of this study is to determine if an informational workshop on pelvic floor disorders administered via a video intervention will increase Spanish‐speaking women's knowledge of pelvic floor disorders and decrease pelvic floor symptoms post‐intervention. Hypothesis or Aim: A single 20 minute video workshop on pelvic floor disorders will improve Spanish‐speaking women's knowledge of pelvic floor disorders immediately post‐intervention and at 4 weeks post‐intervention compared to a pre‐intervention knowledge. Justification of the Study (Background): It is estimated that by the year 2050 in the United States, 58.2 million women will have at least 1 pelvic floor disorder. However, understanding of these disorders among patients is low. Prior studies assessing patient knowledge have shown that participants often did not understand basic urogynecologic terms such as urinary incontinence, pelvic organ prolapse, and pelvic floor disorder and that the participants had poor knowledge of participants' conditions. Latinos will comprise 30% of the population in the United States by year 2060. In Hispanic women, barriers such as lower income, lower education, limited English language proficiency and lack of health coverage influence access to health care. In those with pelvic floor disorders, additional barriers such as poor understanding of general medical conditions, medical terminology, and female anatomy may lead to low understanding of participants' condition, treatment options, and therapies. Given this high prevalence estimate, educating and optimizing care for Hispanic women with such disorders is imperative with implications of having a significant societal impact. Pelvic floor health workshops have previously been shown to be effective in improving postpartum knowledge, performance of pelvic floor muscle exercises, and bowel‐specific quality of life. Learning through a class focused on behavioral modification and pelvic floor muscle exercises for women with urinary incontinence, was shown to be an effective means to educate women about urinary incontinence management. Women's knowledge, symptoms, and quality‐of‐life scores significantly improved at 3 months after undergoing an educational pelvic health workshop on incontinence and pelvic organ prolapse. Currently, no studies have investigated the effects of a formal educational pelvic floor disorder workshop in Spanish on this knowledge or its impact on patient symptoms in those who suffer from pelvic floor disorders at baseline. The investigators research project proposes to close the gap between patient knowledge and scientific knowledge and potentially improve pelvic floor symptoms. The investigators' video workshop will empower women with knowledge and allow the women to make informed decisions surrounding the women's pelvic floor health. It will provide the women with tools to improve the women's own pelvic floor health. A pelvic floor health workshop targeted to Spanish‐speaking women is an innovative concept which could lead to better patient care in a growing population. It may be the first step in prevention of future pelvic floor conditions.

Nct (2021). "Pelvic Floor Disorder Education in Prenatal Care." ClinicalTrails.gov.
	Once verbal consent is obtained, participants will be randomly assigned in a 1:1 ratio to the intervention (video education) or control group (routine prenatal visit only). Group assignments will be performed using computer‐generated randomization. All participants will complete a paper questionnaire including basic demographic information, prior history of pelvic floor disorders, and current PFD symptoms. Participants assigned to the routine prenatal visit only will be instructed to complete the Prolapse and Incontinence Knowledge Questionnaire (PIKQ). The PIKQ is a validated 24‐item questionnaire designed to assess knowledge of PFDs, including two 12‐item subscales on urinary incontinence (PIKQ‐UI) and prolapse (PIKQ‐POP).

Nct (2021). "Pelvic Floor Muscles and Stabilization Integrated Training Improved Pregnancy-related Pelvic Girdle Pain." ClinicalTrails.gov.
	Many women have pregnancy‐related pelvic girdle pain (PPGP), and about 30% with PPGP women still complain of pain after 1‐year postpartum. Both physical and mental functions of PPGP women are impaired. Pelvic stabilization exercise with pelvic floor muscle training is believed to be effective for reducing pain and improved pelvic stability. However, intervention studies on PPGP women is limited and current evidence are controversial. Incorrect pelvic floor muscle activations may be partly contributed to these results. One previous study has showed about 60% of women cannot activate pelvic floor muscles correctly. Transabdominal sonography‐guided biofeedback by observing bladder movements is no‐invasive and benefit learning correct muscle contraction. Therefore, the main purposes for this study are to investigate the effects of pelvic stabilization training using transabdominal sonography‐guided biofeedback in postpartum women with PPGP. A total of 50 postpartum PPGP women will be randomized into one of the two groups: (1) biofeedback group, (2) exercise group, (3) control group, and (4) health group. Subjects in the biofeedback group and exercise group will perform the same exercise training for 8 weeks except the subjects in the biofeedback group will receive transabdominal sonography‐guided biofeedback of bladder movement for the first 4 weeks. The outcome assessment will include the muscle thickness of abdominal muscle and pelvic floor muscle control, functional performance of ASLR fatigue task, timed up and go and fast walking, pelvic girdle questionnaire (PGQ), and numeric rating scale (NRS). It is anticipated that the biofeedback group will have more improvements that the exercise group.

Nct (2021). "Pembrolizumab and Lenvatinib for the Treatment of Serous Ovarian Cancer Patients." ClinicalTrails.gov.
	PRIMARY OBJECTIVE: I. To estimate both the individual and combined effects of pembrolizumab and lenvatinib on T‐cell dysfunction and proliferation in the peritoneal tumor microenvironment (p‐TME) in subjects with high‐grade serous ovarian cancers with peritoneal metastasis. SECONDARY OBJECTIVES: I. To estimate the objective response rate to pembrolizumab and lenvatinib combination in subjects with platinum‐resistant high‐grade serous ovarian cancer. II. To estimate the individual and synergistic effects of pembrolizumab and lenvatinib on T‐cell effector function, improved T cell memory establishment, and myeloid subpopulations in the p‐TME. EXPLORATORY OBJECTIVES: I. To profile the dynamic changes in the immune phenotypes by dissecting the cell types and functional states of various immune cell subsets in the sequential p‐TME samples using single cell ribonucleic acid sequencing (scRNAseq) and investigate changes in peritoneal immune (T‐cells, B cells, natural killer [NK] cells, dendritic cells, neutrophils, tumor‐associated macrophages [TAMs], myeloid‐derived suppressor cells [MDSCs]) and non‐immune cells (fibroblasts, tumor cells) to identify cell subsets that are associated with immune resistance and therapy response. II. To characterize T/B cell immune repertoire and their clonotypic phenotypes in a subset of responders and non‐responders using single cell T‐cell receptor (TCR)/B‐cell receptor (BCR) sequencing (scTCR/BCRseq) simultaneously with scRNAseq. OUTLINE: Patients are randomized to 1 of 2 arms. COHORT A: Beginning cycle 0, patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Beginning cycle 1, patients also receive lenvatinib orally (PO) once daily (QD) on days 1‐21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. COHORT B: Beginning cycle 0, patients receive lenvatinib PO QD on days 1‐21. Beginning cycle 1, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days, every 6 weeks for 1 year, then every 9 weeks thereafter. Patients with confirmed disease progression are followed every 12 weeks.

Nct (2021). "PErsonalized Addition of Recombinant LH in Ovarian Stimulation." ClinicalTrails.gov.
	The main objective of assisted reproductive technology is to achieve a healthy child. Many aspects play a role in order to reach this outcome, including female age, the number of oocytes retrieved after ovarian stimulation, and endometrial receptivity. It has been clearly demonstrated that the number of oocytes obtained after ovarian stimulation for IVF/ICSI is a surrogate marker for the success rates following treatment. In general, a high number of oocytes retrieved is translated into a high number of embryos and eventually a high cumulative pregnancy rate (after the transfer of fresh and frozen‐thawed embryos). However, although a higher number of oocytes and embryos may ensure an increase in the cumulative pregnancy rate, excessive ovarian response has been postulated to have a detrimental effect on the pregnancy rates following fresh embryo transfer given that raised serum estradiol and progesterone levels associated with a very excessive response may negatively affect embryo implantation. In assisted reproductive technology (ART) cycles under the GnRH analog regimens, elevated progesterone serum levels at the late follicular phase, in good ovarian reserve women, is thought to be related to multiple follicular development and increased ovarian steroidogenic activity. However, for these patients elevated progesterone was shown to negatively affect the endometrium preparation and thereby implantation rate. Furthermore, in this group of women elevated progesterone is advocated to have no negative effect on the oocyte or embryo quality. Importantly, more pronounced effect on unbalanced steroidogenesis has been correlated with age and ovarian reserve. For this patient population, serum progesterone/estradiol (P/E2) ratio on the day of human chorionic gonadotropin (hCG) administration was suggested as a more reliable marker predictor to cycle success than solely progesterone rise. Based on the above‐mentioned reports it is relatively clear that the aim of ovarian stimulation should be to result in high oocyte yield and educate endocrine milieu in order to maximize cumulative live birth rates. Nevertheless, despite this goal, a substantial proportion of patients do not manage to reach an optimal oocyte yield, resulting in lower pregnancy rates. These hypo‐responders are associated with low follicles growth and reduced estrogen production leading to longer stimulations, and/or greater cumulative FSH doses. Although, it is widely accepted that poor ovarian responders have significantly low live birth rates as compared with all other groups, an intermediate group of women with a "suboptimal ovarian response", has been recently proposed as a distinct group with significantly worse prognosis from women with normal response. In the same line, the POSEIDON group (Patient‐Oriented Strategies Encompassing IndividualizeD Oocyte Number) has recently proposed a new stratification for patients with a reduced ovarian reserve or unexpected inappropriate ovarian response to ovarian stimulation, taken into account quantitative and qualitative parameters such as: i. Age and the expected aneuploidy rate; ii. Ovarian biomarkers (mainly antral follicle count (AFC) and anti‐Müllerian hormone (AMH)), and iii. Ovarian response to a previous stimulation cycle. One of the most interesting group of patients fulfilling the POSEIDON criteria is undeniably, POSEIDON GROUP 2: Women ≥35 years with adequate ovarian reserve parameters (AFC≥5; AMH≥1.2 ng/ml) and with unexpected poor or suboptimal ovarian response: ‐ Subgroup 2a: <4 oocytes after standard ovarian stimulation. ‐ Subgroup 2b: 4‐9 oocytes after standard ovarian stimulation. Patients belonging to the POSEIDON group 2 are women with an objectively good ovarian reserve who do not manage to respond as expected following ovarian stimulation. Consequently, taking into account that these patients are women who do not respond in accordance to their ovarian reserve following ovarian stimulation, identifying the optimal treatment protocol for these women remains of paramount mportance, namely these patients show slow response to FSH stimulation in terms of estradiol levels and follicle growth, require longer stimulations, and/or greater cumulative FSH doses despite their correct ovarian parameters. In this regard, different gonadotropins used for ovarian stimulation have shown to affect differently late follicular phase hormonal levels. In fact, although the role of LH in the follicular phase of ovarian stimulation is still a matter of debate, it seems that IVF/ICSI cycles under LH activity reach lower progesterone levels on the day of ovulation triggering. However, no study has evaluated late follicular phase progesterone levels in Poseidon 2 group patients receiving recombinant FSH (rhFSH) versus rhFSH and rhLH for ovarian stimulation. Taking into account the above‐mentioned evidence, the investigators set out to perform a pilot study in women with suboptimal response (fulfilling Poseidon 2 criteria), in order to examine whether the addition of rhLH to rhFSH significantly changes late follicular phase progesterone levels as compared to rhFSH alone.

Nct (2021). "Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness." ClinicalTrails.gov.
	Olaparib is a poly‐adenosine diphosphate ribose polymerase (PARP) inhibitor, originally used for the maintenance treatment of women with platinum‐sensitive relapsed breast cancer gene (BRCA)‐mutated high grade serious epithelial ovarian, fallopian tube, or peritoneal cancer, who are in response to platinum‐based chemotherapy. Over the last two years, several therapeutic indications have been added to the drug label, such as first‐line platinum‐sensitive BRCA‐mutated high grade serious epithelial ovarian, fallopian tube, or peritoneal cancer, germline BRCA1/2‐mutated, human epidermal growth factor 2 (HER2‐)negative, locally advanced or metastatic breast cancer and BRCA1/2‐mutated metastatic castration‐resistant prostate cancer, who have progressed following prior therapy. Since olaparib is very expensive, this increase of treatment population will have a significant impact on health care expenditures. To keep healthcare affordable and accessible for all patients, innovative strategies are warranted to reduce the dose of expensive drugs, without reduction of efficacy. For olaparib, pharmacokinetic (PK) boosting can be applied. PK boosting is the lay term for administering a non‐therapeutic active strong inhibitor of a metabolic enzyme, for example the cytochrome p450 enzyme 3A (CYP3A), together with a therapeutic drug that is metabolized by the same enzyme. Boosting thus increases the concentration of the therapeutic drug and allows lower doses to be administered to patients. Hence, coadministration of a reduced dose of olaparib with cobicistat, a non‐therapeutic, strong inhibitor of the CYP3A can lead to equivalent exposure to olaparib. Furthermore, inhibition of CYP3A could lead to less PK variability since metabolic capacity is a prominent cause for (intra‐ and inter‐individual) variability in systemic exposure. Predictable olaparib exposure will reduce the number of patients who are unintentionally under‐ or overtreated. Lastly, tumor tissue itself may express CYP3A as a detoxification or resistance mechanism. Theoretically, PK boosting may also overcome CYP3A‐mediated drug resistance. The purpose of this study is to establish the efficacy, safety and feasibility of co‐administering olaparib with the PK booster cobicistat with the aim to implement boosting approach for olaparib in routine practice. The study is subdivided in two parts. In part A of the study the equivalent exposure of boosted low dose olaparib is determined compared to the normal dose. In part B of the study, non‐inferiority of the boosted olaparib regimen will be confirmed.

Nct (2021). "A Phase II Study of Balstilimab Independently or in Combination With Zalifrelimab in Advanced Cervical Cancer." ClinicalTrails.gov.
	This is an open‐label, multi‐center Phase II clinical trial to assess the efficacy, safety, and pharmacokinetics of Balstilimab (Treatment Arm 1 ‐ monotherapy) or in combination with Zalifrelimab (Treatment Arm 2 ‐ combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first‐line platinum‐based chemotherapy.

Nct (2021). "A Phase III Study to Evaluate Efficacy and Safety of First-Line Treatment With HLX10 + Chemotherapy in Patients With Advanced Cervical Cancer." ClinicalTrails.gov.
	The purpose of this study is to assess the efficacy and safety of HLX10(Recombinant Anti‐PD‐1 Humanized Monoclonal Antibody Injection) plus chemotherapy compared to the efficacy and safety of placebo plus chemotherapy in the treatment of adult women with persistent, recurrent, or metastatic cervical cancer. Chemotherapy regimens include: paclitaxel plus cisplatin and paclitaxel plus carboplatin. The primary study hypotheses are that the combination of HLX10 plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression‐free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the IRRC or, 2) Overall Survival (OS).

Nct (2021). "Platelet Rich Plasma in Women With Urinary Incontinence." ClinicalTrails.gov.
	Stress urinary incontinence (SUI) is defined as involuntary loss of urine on effort or physical exertion or on sneezing or coughing. Platelet‐rich plasma (PRP) is an autologous solution of human plasma containing various growth factors witch enhance regeneration and healing process. The aim of this study is to evaluate the efficacy and safety of PRP in the treatment of the female SUI.

Nct (2021). "Post-Hysterectomy Nursing Support Program." ClinicalTrails.gov.
	Aim: This study was conducted to evaluate the effectiveness of the nursing support program developed for women who had hysterectomy. Methods: A prospective, randomised controlled study was conducted in the gynaecology clinic of a university hospital between November 2017 and November 2018. It was conducted in a single‐blind, randomised controlled trial with a total of 60 women in the experimental and control groups. A nursing support program had been developed for women who have had a hysterectomy. The program developed for the experimental group and the routine program for routine maintenance and control group were applied. The initial evaluation was carried out postoperative on the 1st‐2nd day, the second assessment was carried out on the 6th‐7th day and the third evaluation was carried out at 2 months. The first interview was carried out in the hospital, and the second and third interviews were carried out with home visits. The sociodemographic data form, postoperative evaluation form, Female Sexual Function Index (FSFI), Epidemiological Studies and Central Depression Scale (EAMDS), Menopausal Symptoms Evaluation Scale (MSDS) and SF‐12 quality of life scale were used to collect data.

Nct (2021). "Postoperative Pain Score of Laparoscopic Gynecological Surgeries." ClinicalTrails.gov.
	In this prospective randomized study, Baskent University Adana Dr. Turgut Noyan Application and Research Center for benign reasons (myomas that cause abnormal uterine bleeding, resistant to medical and hysterescopic surgery, treatment‐resistant adenomyosis in which the uterus reaches 12 weeks of gestation, recurrent endometrial hyperplasia, endometriosis, stage 1 endometrial cancers that only underwent hysterectomy) in laparoscopic hysterectomies; at the entrance to the abdomen, it is planned to apply the umbilicus, which is the anatomical route, to some of the patients, and to the other part of the sub‐umbilicus incision. It will be compared in terms of pain score on the 8th hour and 1st day after surgery. The minimum quorum for each group was determined by calculating 41 and taking a total of 82 patients. The simple randomization technique will be applied in the distribution to the study sets. Based on the studies, it is thought that the anatomical path may be less painful.

Nct (2021). "Postpartum Depression and Maternal Attachment." ClinicalTrails.gov.
	Sample Power analysis was performed to determine the number of samples. For this, the information in a similar study (Aydın Özkan et al., 2020) was used as a reference. The minimum number of participants required to be included in each group was determined as 24, with a total of 48 (α=0.01, 1‐β=0.95). However, considering the loss rate (18.75%) in Aydın Özkan's study, which was taken as a reference, the total number of participants was determined as 56 (experimental: 28, control: 28). Randomization In order to prevent imbalance between the groups, pregnant women will be assigned to the experimental and control groups by the tanned block randomization method. Pregnant women will be stratified according to parity (primiparous‐multiparous) and Edinburgh Postpartum Depression Scale score (0‐9 points, 10‐30 points). In this context, 8 groups will be formed as shown below. Set 1: Primiparous and pregnant women with EPDS scores between 0 and 9 Set 2: Primiparous and pregnant women with a EPDS score of 10‐30 Set 3: Multiparous and pregnant women with EPDS score between 0 and 9 Set 4: Multiparous and pregnant women with a EPDS score of 10‐30 Data Collection Personal Information Form, Prenatal Attachment Scale, Edinburgh Postpartum Depression Scale and Postpartum Attachment Scale will be used to collect data. The purpose and content of the study will be explained by interviewing 35‐week‐old pregnant women who applied to FHCs for pregnancy follow‐up. Their compliance with the sampling inclusion criteria will be evaluated. Then, an informed consent form will be signed by the pregnant women who agree to take part in the study. Personal information form, Prenatal Attachment Scale and Edinburgh Postpartum Depression Scale will be administered to pregnant women participating in the research. Then, the pregnant women will be randomized by stratified blocking according to their parity and EPDS score averages, and the assignment of the experimental and control groups will be made. Contact information (Phone numbers and e‐mail addresses) will be taken at the first encounter.Experimental Group Application 36‐37 with pregnant women in the experimental group. There will be a total of two online interviews, once a week, starting from the first week. Before the first interview, women will be sent a PKGE video explained by the researcher via e‐mail or Whatsapp application, and they will be asked to watch it before the interview. In the first meeting, basic information about postpartum depression and what to do to prevent postpartum depression will be explained. The women will then be asked to describe the PKGE. The interview will be terminated when it is confirmed that the women have understood correctly and fully. Afterwards, "Relaxation Exercises CD Audio Recordings" belonging to the Turkish Psychological Association will be sent to the women, and they will be asked to do PCGE at least 3 days a week until delivery, accompanied by the instructions on the CD. In the second meeting; If postpartum depression develops, what should be done and maternal attachment will be explained, and women's opinions and questions about PCGE will be taken. In this interview, women will be asked to continue PCGE at least 3 days a week from the day they feel ready, starting at the latest 1 week after delivery. During the application process to women, "Don't forget to do your relaxation exercise" every other day, "Weekdays to talk to your nurse about the training issues you have received. Weekend …. You can call or send a message about the issues you want to consult between the hours of the day. message will be sent. If the woman wants to have an interview, she will be called at the specified times and interviewed and the participant's questions will be answered. If it is noticed that an issue that needs help from different disciplines or that a postpartum complication develops, he will be referred to the hospital. The Edinburgh Postpartum Depression Scale and the Postpartum Attachment Scale will be administered at the sixth week ostpartum. The scales will be converted into an online questionnaire and mothers will be asked to fill in by sending their contact address. Control group application Prenatal Attachment Scale and Edinburgh Postpartum Depression Scale will be administered to women at 36 weeks of pregnancy, Postpartum Attachment Scale and Edinburgh Postpartum Depression Scale will be administered to women at 6 weeks postpartum. The scales will be converted into an online questionnaire and women will be asked to fill in by sending their transportation address. No intervention will be applied to the women in the control group during the study.

Nct (2021). "Postpartum Pelvic Floor Workshop." ClinicalTrails.gov.
	There is compelling evidence for the need for perineal education and care, especially in women who have recognized risk factors. For example, 30‐50% of women who have a clinically recognized risk factor report anal incontinence, fecal urgency, dyspareunia and perineal pain. Despite this, a study found that less than 50% of women with anal incontinence voice those symptoms unless directly asked about them. Some authors discuss how women may not share these symptoms with their care providers out of the belief that it is a "normal" effect of childbirth. A review of the literature shows that antenatal educational workshops can be an effective means to provide pregnant women with information regarding pelvic floor health, including how modes of delivery impact pelvic floor function. Similarly, antenatal pelvic floor workshops have been found to improve patients' knowledge on pelvic floor health, their practice of pelvic floor muscle exercises and their confidence with these exercises. To our knowledge, there is no literature exploring the role of a postpartum pelvic floor workshop, on managing perineal and pelvic floor symptoms in women who are identified as being at higher risk of developing pelvic floor dysfunction. Our goal is to develop and assess such a workshop.

Nct (2021). "Postpartum Video Education." ClinicalTrails.gov.
	Prior to the day of postpartum discharge, a designated staff person will approach eligible patients and review the objectives of the study. If patients are willing to participate, they will complete a consent form and the baseline questionnaire. The baseline questionnaire will assess patient knowledge on postpartum hemorrhage, infection, hypertensive disorders of pregnancy, and depression. Following delivery, patients will be randomized. Randomization will be done in a 1:1 allocation ratio between written discharge instructions + video education vs. written discharge instructions (standard of care at YNHH). A computer algorithm will assign participant based on random permuted blocks design with block size between 2‐4. Each participant will have an assigned Study ID number that is linked to their random assignment. Group 1 will be the written discharge + video education group (intervention group). Group 2 will be the written discharge education (control group). On the day of discharge, the nursing staff will provide discharge education based on their randomized group: Group 1 will be the written discharge education + video education group (intervention group). These patients will view a 12‐minute educational video on SMM warning signs, in addition to the written discharge instructions provided by nursing staff. At the completion of the video, they will complete a post‐video questionnaire to assess their knowledge on the covered topics. Group 2 will be the written discharge instruction group (control group). They will receive the written discharge instructions provided by nursing staff and complete the post‐discharge instruction questionnaire. Following discharge, patients will complete a post‐discharge questionnaire to assess knowledge retention on the covered topics. Patients' antepartum, delivery, and postpartum course will be reviewed until 1 year postpartum, including outpatient visits, emergency department visits, and any hospitalizations. All subjects will be assigned a unique study ID code upon enrollment. Data will be collected from patients' medical records and from self‐report. It will be recorded/stored in REDCap and on a Yale server accessible only to members of the research team. All data will be de‐identified at the conclusion of chart review. Data analysts will have access to only de‐identified information.

Nct (2021). "Pre-incision Versus Post-incision Local Anesthetic During Robotic Sacrocolpopexy." ClinicalTrails.gov.
	Pelvic organ prolapse is becoming more common as women's life expectancy is increasing and the prevalence of obesity is rising. Many women undergo pelvic reconstructive surgery to treat their prolapse and improve their quality of life. The incidence of pelvic organ prolapse is 1.5‐1.8 surgeries per 1,000 women years. Approximately 300,000 pelvic reconstructive surgeries are performed each year in the United States. There is a wide variety in surgical approaches and procedures for prolapse. One such procedure is a sacrocolpopexy in which the cervix or vaginal cuff is lifted to the anterior longitudinal ligament overlying the sacrum via a mesh graft. This can be done in a minimally invasive fashion with a laparoscopic or robotic approach or in an open abdominal approach. Numerous studies have shown this procedure to have a high success rate and long‐term durability. As robotic/laparoscopic approach to surgery has shown shorter hospital‐stays and improved patient outcomes, the robotic‐assisted sacrocolpopexy has been rapidly incorporated into clinical practice. In general, surgery causes a release of painful chemical mediators which has led to increased narcotic use, increased narcotic addiction, and number of pills prescribed. Most individuals who undergo surgery will require narcotics postoperatively to control their pain and some individuals have to extend their hospital stay until adequate pain control is achieved. Our study is aimed to reduce narcotic use, decrease hospital stay due to pain issues and determine if timing of adjunct pain medication improves pain scales for patients. As postoperative pain after minimally invasive surgery is complex, specialists suggest that the effective analgesic treatment should be a multimodal approach. Use of local anesthetic with bupivacaine at robotic/laparoscopic trocar sites is the standard of care, however, there is no standard as to optimal timing that is most beneficial for patients to decrease pain. Currently, bupivacaine is used by providers at the trocar sites at either the beginning of the case or at the end of the case. From clinical observation, it appears that postoperative pain levels reported from patients receiving either at the beginning of surgery (pre‐) or end (post‐incision) of the surgery are similar. This study aims to examine the difference in postoperative day one pain levels reported by patients between the two infiltration methods

Nct (2021). "Premenstrual Syndrome (PMS) and Mindfulness Stress Reduction Program (MSRP)." ClinicalTrails.gov.
	Premenstrual syndrome (PMS) is a disorder characterized by emotional, physical and behavioral symptoms that increase the severity of the menstrual cycle in women of reproductive age during the luteal phase and disappear spontaneously a few days after the onset of menstruation. It is stated in the literature that more than 40 million women experience PMS symptoms. While PMS significantly affects 20% of women's daily lives, it manifests itself as mild premenstrual symptoms in 90% of women. It is stated that PMS is associated with more than 300 physical, psychological, emotional, behavioral and social symptoms. These symptoms can include changes in appetite, weight gain, abdominal pain, backache, lower back pain, headache, breast swelling and tenderness, nausea, constipation, anxiety, irritability, anger, fatigue, restlessness, mood swings, and crying. Therefore, premenstrual symptoms can negatively affect individuals' participation in courses, school success, social activities and family relationships. Recently, in addition to pharmacological applications, non‐pharmacological applications are frequently preferred to reduce premenstrual symptoms (reflexology, acupuncture, acupressure, music, mindfulness). Mindfulness is defined as directing one's non‐judgmental attention to thoughts, feelings, bodily sensations, and interactions. It has been stated that with the meditation practices of mindfulness, individuals experience less anxiety, depression, anger and lower levels of psychological distress, including anxiety. . PMS is an important health problem with complex symptoms. To cope with these symptoms, PMS needs to be addressed in a multidimensional way. It is thought that the mindfulness stress reduction program can reduce the symptoms of PMS by regulating the stress level and emotional balance of women. When the domestic studies were examined, there was no study that evaluated the effect of mindfulness stress reduction program on PMS, while when the foreign literature was examined, it was determined that there were studies conducted in a limited number and with a small sample, in which the effect of mindfulness stress reduction program on PMS was evaluated. This research was planned as a single‐blind randomized controlled experimental study to evaluate the effect of mindfulness stress reduction program on the reduction of premenstrual symptoms in coping with premenstrual syndrome.

Nct (2021). "Preoperative Analgesia by Infiltration of the Pudendal Nerve Prior to Sacrospinous Ligament Suspension." ClinicalTrails.gov.
	Study Procedures: Randomization and Blinding: Women will be randomized to receive either Bupivacaine 0.25% or Normal Saline pudendal injections based on the label within a sealed envelope randomly selected on the day of their surgery. Fifty labels will be created with twenty‐five labels each of "Bupivacaine 20ml" or "Normal Saline 20ml" written on them. These will be placed in blank, identical envelopes and sealed and shuffled prior to the start of the study. Upon selection, the sealed envelope will be given to the circulating nurse who will draw up the selected solution and label it "pudendal block". The circulating nurse will be directed to not disclose the contents of the envelope or syringe to the participant or to any other member of the team. They will then re‐seal the envelope with tape, place a patient label on it and return it to the surgical team post procedure to be returned to a locked file cabinet within the surgical office at the end of the day, to be kept securely with medical records. Group allocation envelopes will be opened after the collection of all outcome data is complete to allow for data analysis. In order to avoid local anesthetic toxicity, any calculations for other anesthetic agents utilized for the surgical procedure or anesthetic will assume that 20 ml of 0.25% Bupivacaine was administered. In the event that an emergent adverse complication is identified which may be attributable to the administered agent, the treatment allocation can be unblinded if this is deemed clinically necessary by the investigator or other treating physician. In the event this is required, the patient will be withdrawn from the study and excluded from the final analysis, but such case(s) will be described in the final study results. The circulating nurse already draws up local anesthetic and normal saline as a routine part of this procedure for use in other ways, and so the investigators do not anticipate that their participation in this study will be a large burden of work. The investigators estimate that it will add no more than 2 minutes to their preparation time for the surgery. Pudendal Block administration: The Pudendal block will be administered by the Surgeon or Surgical Fellow after the administration of anesthetic and preparation for surgery but before the first surgical incision. It will be administered with standard transvaginal technique. Standardization of the Anesthesia, Pre‐op and postoperative pain management: Pre‐operative, postoperative and intra‐operative care will be standardized according to guidelines that meet criteria for current standard of care as outlined in the appendix. These pages will be printed on the chart to identify the patient as a participant in the study and also to remind the surgical and anesthetic team of the guidelines of the study. Standardization of postoperative pain management after discharge: All patients will receive the same instructions for management of postoperative pain. They will receive instructions to use acetaminophen (Tylenol) regularly as well as Ibuprofen (Advil) regularly as long as they have no contraindications or allergies to these medications. They will be given a standardized prescription for tramadol to use in addition to these medications for management of breakthrough pain. Study and Follow up Visits: The patient will have no additional visits attributed to their participation in this study. Instead they will receive electronic (email or text) surveys and telephone reminders over a period of 2 weeks after their operation. The first survey will take less than 1 minute to complete, the second will take less than 5 minutes to complete, and the final survey less than 10 minutes to complete.

Nct (2021). "Prevention of Postpartum Depression: a Pilot Placebo-controlled Trial of Trazodone." ClinicalTrails.gov.
	Postpartum depression is a serious illness that affects approximately 17% of women who have recently given birth. Untreated depression appears to have negative effects for both the mother and her baby. Postpartum depression is quite common among women with a history of depression. Sleeplessness is a common concern during pregnancy and after delivery, and it can also trigger depression in women with a history of depression. Antidepressants are the most commonly recommended drugs for prevention of postpartum depression; however, there is limited research to understand the effectiveness of the medications in preventing postpartum depression. Trazodone is a weak antidepressant, but it is commonly prescribed for sleeplessness due to physical or psychiatric disorders. We are planning a study to find out whether trazodone in a low dose is more effective than a sugar pill in preventing postpartum depression among women with histories of depression. We expect the results of our study will make it easier for healthcare providers to select the right medication for women who are at risk of developing depression after delivery and thus improve the mental health of mothers and well‐being of their babies.

Nct (2021). "Primary Dysmenorrhea and Osteopathic Treatment." ClinicalTrails.gov.
	It will be a prospective study, a double‐blind randomized controlled clinical trial. The sample group will include 60 patients, between 18 and 30 years old divided into two experimental groups. The experimental group (n = 30) will be treated following an osteopathic treatment, through a bilateral global pelvic manupulation (GPM) and a specific internal technique for mobility of the cervix, and the control group (n = 30) will only carry out a bilateral GPM. A measurement will be made before the first treatment, another after each session, and the last one two weeks after the last intervention (anthropometric measurements, quality of life questionnaire, sexual health, osteopathic tests, pressure point with algometer, pain and medicines consumption). The established outcome measures are: pain intensity according to the visual analog scale (VAS), depression points measured with an algometer, a health‐related quality of life questionnaire, questionnaire sexual health and sexual dysfunctions, and the measurement of drug consumption.

Nct (2021). "PROfiling Based Endometrial Cancer Adjuvant Therapy." ClinicalTrails.gov.
	Adjuvant therapy for women with endometrial cancer has increasingly been tailored to prognostic factors to prevent overtreatment and select those women for adjuvant treatment who will have a clinically relevant reduction of the risk of relapse by the adjuvant treatment. Risk profiles have traditionally been based on clinicopathological factors such as age, stage, grade, Lymph‐Vascular Space Invasion (LVSI) and depth of invasion. Newer, both molecular‐genetic (the cancer genome atlas subgroups) have become available which are strongly related to outcomes and risk of cancer spread. Based on 2022 National Comprehensive Cancer Network (NCCN) guideline and the ongoing "Portec‐4a" trial, this randomized trial using integrated genomic‐pathologic classification to assign adjuvant treatment for women with stage I‐II high‐intermediate and intermediate risk endometrioid adenocarcinoma.

Nct (2021). "Quality of Life Interventions During Cervical Cancer Treatment." ClinicalTrails.gov.
	Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation‐related side effects, and immunosuppression. This prospective randomized clinical trial proposes to examine the effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for (1) supporting cellular immunity, (2) improving mood and quality of life (QOL), and (3) reducing treatment‐associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation.

Nct (2021). "Randomized Comparison Between Sentinel Lymph Node Biopsy and Lymph Node Dissection in Early Stage Endometrial Cancer." ClinicalTrails.gov.
	The standard treatment for endometrial cancer is total hysterectomy and bilateral salpingo‐oophorectomy, peritoneal cytology, and lymph node dissection. Pelvic lymph node dissection helps to set accurate staging and adjuvant therapy group, but it has never been proven to have therapeutic effects by itself. According to the results of two recent randomized clinical trials, routine pelvic lymph node dissection in early stage endometrial cancer doesn't improve survival rates. Routine pelvic lymph node detection can cause complications in a large number of patients and is associated with poor quality of life. Therefore, it is important to develop a method that can check the status of the lymph node in a less invasive way. Efforts have been made to preserve other lymph nodes with significantly less potential for metastasis through less invasive methods, reducing lymph edema and complications such as bleeding and nerve damage caused by excessive surgery. Sentinel lymph node dissection is used as a standard treatment for breast cancer and malignant melanoma, and efforts to develop it have recently continued in endometrial cancer and cervical cancer. A SENTICOL study conducted in cervical cancer patients showed a false‐negative rate of 0% when both were monitored lymph node dissection. In addition, unlike routine pelvic lymph node dissection, ultra‐staging through 0,2mm gas intercepts allow additional detection of less than 2mm of microtransfer or less than 0.2mm of independent tumor cells that have not been found before. In a recent large‐scale prospective study of endometrial cancer, sentinel lymph node mapping using indocyanine green and fluorescent imaging was successful at 86%, and sensitivity (patient‐by‐patient analysis) reported 100% in diagnosis of lymph node metastasis. As laparoscopic and robotic surgery account for most of the treatment of endometrial cancer patients, a good environment is created for monitoring lymph node exploration using ICG, and sensitivity and detection rate seem to have improved compared to the previous method. However, there has been no prospective study on the effects of patient clinical prognosis, such as a standard treatment, pelvic lymph node resection, and disease‐free survival rate, and overall survival rate, so a prospective study is essential. The investigators compare survival rates in the group that does sentinel lymph node mapping and routine pelvic lymph node detection in endometrial cancer in clinical stage I‐II.

Nct (2021). "Randomized Controlled Trial of Combined Letrozole and Clomid (CLC II) Versus Letrozole Alone for Women With Anovulation." ClinicalTrails.gov.
	Letrozole and Clomid are both used for ovulation induction, but they have different mechanisms of action. In a pilot study we found that the combination of letrozole 2.5 mg and CC 50 mg nearly doubled the ovulation rate as compared to use of letrozole monotherapy (77% vs. 43%, P=0.007; rate ratio for ovulation (95% CI) 1.80 (1.18 to 2.75), with similar endometrial thickness and number of follicles across treatment arms among those who ovulated. Additional data is needed to evaluate escalating dosages, multiple cycles, live birth and multiple gestation with this novel treatment combination. This is a randomized controlled trial of letrozole versus letrozole and clomiphene citrate (CC) for up to three menstrual cycles. Women will be randomized in a 1:1 ratio to receive letrozole 2.5 mg or combination of letrozole 2.5 mg and clomiphene 50 mg for 5 days on days 3‐7 of menstrual cycle. The women and their partners will be instructed to have regular intercourse with the intent to conceive during the cycle. Patients will have an transvaginal ultrasound in the mid‐luteal phase of cycle to assess corpora lutea number and endometrial thickness. Patients will have mid‐ luteal phase progesterone level drawn to evaluate ovulation. Patients in both study arms who do not ovulate will have their Letrozole dose increased by 2.5 mg in the next study cycle to a max of 7.5 mg. Patients in the combination arm who do not ovulate will only have their Letrozole dose increased and will continue to receive the same dose of clomiphene across the three study treatment cycles. Side effect profile will also be monitored.

Nct (2021). "Rectal Prolapse With ODS. STARR vs LVR." ClinicalTrails.gov.
	This randomized controlled trial (single center, prospective, randomized controlled, parallel, and single‐blind trial) is designed to compare the outcome of patients with ODS and rectal prolapse undergoing transanal prolapsectomy with mechanical stapler (STARR) versus laparoscopic ventral rectopexy (LVR), with the aim of evaluating the most appropriate surgical choice. The study will be conducted at the Surgical Unit 2 of the University Hospital of Ferrara, Italy. Patients suffering from rectal prolapse and ODS that will refer to the colorectal and pelvic floor clinic of the University Hospital Ferrara, and eligible for surgery, will be evaluated consecutively after expressing consent to participate in the study by signing an informed consent. The duration of the study for each patient will be expected to be 48 months with follow‐up at 1, 3, 6, 12, 24, 36, and 48 months postoperatively. Eligible patients will receive information about participating in the trial by their surgeon. Consecutive eligible patients will be randomly assigned to one of two groups with a 1:1 equal allocation ratio. Patients eligible for the study will be randomized on a 1:1 basis to undergo transanal prolassectomy (Group 1: STARR) or laparoscopic ventral rectopexy with mesh placement (Group 2: LVR). An independent individual will perform randomization using a software randomization program. Randomization will be performed by a randomized list. The assignment sequence will be generated from a random numerical series generated through a computerized list. Randomization will be in blocks of 4. Group assignments will be unknown to those responsible for data collection and those who will be responsible for statistical analysis and clinical evaluation of patients. The diagnosis of ODS will be attributed after clinical evaluation at the colorectal clinic and on the basis of the presence of one or more symptoms associated with this disorder, such as to reach a score of 14 and above according to the validated score of ODS of Altomare. Assessment After recruitment and consent, all patients under study will be asked and collected demographic and clinical information with comorbidities (in particular diabetes, fibromyalgia, depressive disorders, neurological diseases, COPD), parity, previous pelvic surgery, type of surgery, time of hospitalization and any complications (according to Clavien‐Dindo classification). Data concerning the grade of rectoanal prolapse, according with Oxford Classification [20], and rectocele grading will be collected through outpatient proctological evaluation associated with proctoscopy, rectal manometry, and Rx defecography. Colonoscopy will be also performed in every patient to exclude colorectal cancer. The severity of the ODS will be scored with the Altomare's ODS scoring system. Constipation and fecal incontinence will be measured by obtaining their scores through the administration of validated questionnaires such as the Wexner Constipation score, and the Cleveland Clinic Fecal Incontinence Score (CCFI). Quality of life will be also evaluated by the patient assessment of constipation quality‐of‐life (PAC‐Qol) questionnaire. The study of eventually associated pelvic distress will be assessed by administering validated questionnaires such as the Pelvic Floor Distress Inventory (PFDI‐score, short form) and the Pelvic Floor Impact Questionnaire (PFQI‐score, short form). The scores obtained, as well as the presence of symptoms (fecal incontinence, constipation, or ODS) will be calculated before and after surgery (at 6, 12, 24, 36, and 48 months). All patients will be followed up on an outpatient basis at 7 days, 1 month, 3 months, 6 months, 12 ,24, 36, and 48 months after surgery. Rectal manometry and defecography will be performed after 12 months after surgery. Surgical intervention All the procedures will be performed by a single surgeon (SA). The LVR technique used for this protocol is as previously described. Subjects randomized to this arm will receive a standard LVR. Briefly, the peritoneum is opened ov the right side of the sacral promontory. The mesorectum is dissected and extended in an inverted J‐form along the right side. The rectovaginal septum is opened to the pelvic floor. Biologic mesh (Permacol) is sutured to the ventral aspect of the rectum with non‐readsorbable stitches. The proximal end of the mesh is fixed on the anterior longitudinal ligament at sacral promontory with nonabsorbable tacks. The incised peritoneum is then closed to over the mesh. Subjects randomized to STARR arm will undergo a STARR procedure. Briefly, a circular anal dilator is introduced into the rectum. The purse‐string anoscope is used to complete the anterior hemi‐circumference purse‐string suture, about 2‐3 cm above the haemorrhoidal apex. A 33‐mm circular stapler (Ethicon, ppH01) is opened, inserted until crossing the purse‐string which is then tied with a knot. Then the stapler is closed and fired. The same hemi‐circumference purse‐string suture is performed in the posterior rectal wall. A second application of the stapler on the posterior wall is inserted, closed and fired. The duration of the study will be 2 years. The study will be conducted in accordance with the principles of Helsinki Declaration, with approval of the medical ethics review board of S. Anna University Hospital. A written informed consent will be obtained from all enrolled patients. The report will comply with the strengthening the reporting of randomized studies (CONSORT).

Nct (2021). "Red Clover Isoflavones in Postmenopausal Women With Urge Urinary Incontinence and Overactive Bladder." ClinicalTrails.gov.
	The purpose of this study is to investigate the effect of red clover isoflavones in postmenopausal women with and without urge urinary incontinence and overactive bladder

Nct (2021). "Reduction in Number of Botox Injections for Urgency Urinary Incontinence." ClinicalTrails.gov.
	English speaking women ≥21 years old with idiopathic refractory urgency urinary incontinence who have failed first and second line treatment (life style modifications and antispasmodic medications) who are undergoing a first injection of intra‐detrusor Botox will be recruited to participate in this study. Failure of first and second line treatment will be defined as no improvement in urgency urinary incontinence episodes after trial of lifestyle modifications and use of at least one antispasmodic agent. Patients who are planning to undergo her first intra‐detrusor Botox procedure for refractory idiopathic urgency urinary incontinence at the University of Virginia Pelvic Medicine and Reconstructive Surgery clinic will be approached for inclusion into the study. A study overview, as well as risks and benefits, will be reviewed with the patients. The patient will be screened for inclusion/exclusion criteria. If she meets criteria and agrees to study participation, she will be consented for study participation and the Botox injection procedure. Prior to receiving treatment, patients will complete a 3‐day voiding diary and the following questionnaires: Incontinence Impact Questionnaire short form (IIQ‐7) and Urogenital Distress Inventory short form (UDI‐6) at the time of consent. As part of usual care, patients in both arms will receive prophylactic antibiotics (oral nitrofurantoin or cephalexin) to complete prior to the procedure date. On the day of treatment, patients will have a clean catch urine specimen obtained and urine dip completed. Patients who have a positive urine dip will have her procedure rescheduled to another day. A positive urine dip is defined as + leukocytes and + blood in the presence of symptoms of urinary tract infection (dysuria, increased urgency/frequency above baseline or hematuria). In this study, we will not offer patients pre‐procedure oral Valium as it may affect reporting of pain scores. Patients in both arms will be prepared for the procedure in the same fashion: 50 cc of 1% lidocaine will be instilled into the bladder at least 20 minutes prior to the procedure. Patients will then be prepped and draped in the standard fashion. A 70‐degree cystoscope will be inserted through the urethra and into the bladder until the trigone is identified; the bladder will be distended with approximately 200 mL sterile saline. 100 units of Botox will be mixed with 10 mL of Normal Saline for sterile injection into the bladder. In the reduced protocol arm, a single row of 5 injections will be administered into the detrusor muscle. In the standard protocol arm, 3 rows of 5 injections will be administered into the detrusor muscle. In both arms, a final injection with 1 mL of normal saline flush will be injected to remove any residual Botox from the injection needle. The patient will be monitored for 20 minutes post procedure to ensure adequate ability to void after treatment. Approximately 5 minutes post‐procedure, patients will rate their pain experienced during the procedure using a 100‐point visual analog pain scale. If the patient is unable to void post‐procedure, she will be taught how to perform clean intermittent self‐catheterization (CISC) and provided with a log to record void and catheter volumes. She will be called on a weekly basis by the study team to review void/catheterization volumes and encouraged to discontinue when she has 2 successive catheterization volumes of <150 ml. This is in accordance with standard clinical care in our practice. At 2 weeks post procedure, patients in both treatment arms will be interviewed by phone to report results of a 3‐day voiding diary (Aim 1), complete the IIQ‐7 and UDI‐6 again, as well as the OAB Treatment Satisfaction Questionnaire (OAB‐SATq), Client Satisfaction Questionnaire (CSQ‐8)10, Patient Global Impression of Improvement (PGI‐I) questionnaire and evaluate for complications (Aim 2, Aim 3). The same evaluation process will be repeated at 3 months and 6 months post procedure. After completion of all questionnaires at h 4 timepoints (Pre‐procedure, 2 weeks, 3 months, 6 months), patients will receive a $50 incentive for their time and participation.

Nct (2021). "Repetitive Transcranial Magnetic Stimulation in Women With Overactive Bladder With Urgency Incontinence." ClinicalTrails.gov.
	Eligible participants with OAB and UUI will undergo resting state functional MRI of the brain to map baseline brain activity. Participants will then undergo rTMS of the SMA with electromyography (EMG) monitoring of the pelvic floor muscles. They will then undergo another MRI to assess and changes in brain activity due to rTMS. Participants will be asked about their bladder symptoms over the course of the study. The study will have a crossover design. The investigators plan to recruit 10 women with symptoms of OAB and UUI. During the first week, participants will be screened, asked to fill out a bladder questionnaire, and to complete a bladder diary. During the next two weeks, participants will undergo rTMS and functional MRI of the brain to assess brain activity. All participants will undergo two different known rTMS protocols for the pelvic floor, high‐frequency and low‐frequency, separated by a 1‐week washout period. Each participant will be randomized to which protocol they will have first. In total, 5 participants will have started with high‐frequency rTMS first and 5 participants will have started with low‐frequency rTMS. At the end, all participants will have undergone both high‐ and low‐frequency rTMS. The primary objective of the study is to assess the feasibility of rTMS in patients with OAB and UUI, which will be assessed with recruitment and retention rates of participants. The investigators also aim to determine if SMA activity mediates OAB symptoms and pelvic floor muscle tone using functional MRI of the brain. Finally, the investigators want to assess bladder symptoms following rTMS using participant questionnaires and number of UUI episodes.

Nct (2021). "Robotic Versus Laparoscopic Surgery for Deep Endometriosis." ClinicalTrails.gov.
	The objective of this prospective, randomized trial is to examine whether robot‐assisted laparoscopy is superior compared to conventional laparoscopy as regards to patient outcome at 6, 12 and 24 months postoperatively, measured by questionnaires concerning the pain symptoms and disease‐related quality‐of life.

Nct (2021). "The Role of Transcutaneous Electrical Nerve Stimulation (TENS) for Menstrual Pain Relief." ClinicalTrails.gov.
	The present study aims to verify the analgesic potential of a transcutaneous electrical nerve stimulation (TENS) device using patients with primary dysmenorrhea and compare it with a control period without usage.

Nct (2021). "The Role of Vitamin D Supplementation on Pain in Women With Primary Dysmenorrhea and Hypovitaminosis D." ClinicalTrails.gov.
	This study is aimed to be conducted in randomised controlled trial, comparing between intervention group and placebo group. We include women with primary dysmenorrhea who also have low vitamin D level in this trial. Our primary outcome is to compare visual analog pain scale between intervention and placebo group after treatment. After randomised and allocated, these women will be given vitamin D 50,000 IU or placebo capsules orally weekly for 8 consecutive weeks. We monitor pain score daily from the cycle before the drugs started until complete 8‐week course of the regimen mentioned. Also vitamin D levels will be monitored twice, one before treatment and the other after treatment.

Nct (2021). "Secondary Cytoreductive Surgery in Platinum-resistant Recurrent Ovarian Cancers." ClinicalTrails.gov.
	Baseline postoperative imaging with the use of abdominopelvic CT or MRI was to be completed during a 28‐day window in which chemotherapy was initiated. Disease is also assessed after cycles 3 and 6 of trial treatment (and after cycle 8, if administered), every 3 months for 2 years, and then every 6 months thereafter. Physical examinations will be performed, and serum CA‐125 levels measured at the beginning of each cycle of chemotherapy. Treatment‐free interval (6 to 12 months or >12 months after the last chemotherapy infusion) will be reported.

Nct (2021). "Sequencing and Combination of Mirabegron and TTNS in Overactive Bladder Syndrome: a Multicenter, Randomized, Open-label, Crossover Trial." ClinicalTrails.gov.
	Study design: Prospective, randomized, multicenter, open‐label, cross‐over trial Treatment sequence: randomized with 1:1 ratio to either Sequence A or Sequence B Sequence A: mirabegron 50mg monotherapy x 8 weeks ‐> multi‐modal combination treatment x 4 weeks ‐> TTNS monotherapy x 8 weeks Sequence B: TTNS monotherapy x 8 weeks ‐> multi‐modal combination treatment x 4 weeks ‐> mirabegron 50mg monotherapy x 8 weeks Patient population: adults ≥ 20 years who have experienced symptoms of OAB, as defined by International Continence Society (ICS) diagnostic criteria, for at least 3 months Sample size: approximately 180 patients

Nct (2021). "Single Dose of Antenatal Corticosteroids for Pregnancies at Risk of Preterm Delivery (SNACS)." ClinicalTrails.gov.
	Preterm infants are at risk of mortality and morbidity. Antenatal corticosteroids (ACS) reduce the risks of neonatal death and morbidities, such as respiratory distress syndrome. The standard of care for pregnant people at risk of preterm birth includes 2 doses of Celestone to accelerate fetal lung maturity (total 24 mg in Canada, 22.8 mg in Australia). There are no published clinical trial data on the benefits or risks of a single dose of antenatal corticosteroid vs. standard double doses (Ninan et al JOGC 2020). Pregnant people at 22 weeks and 0 days to < 34 weeks and 6 days' gestation at risk of preterm birth with a singleton or twin gestation who have received the first dose of Celestone and consented to the trial will be randomized to receive approximately 24 hours later either an experimental placebo injection (of normal saline) or the standard double dose of Celestone to determine whether the intervention is non‐inferior for the primary outcome of a composite of perinatal mortality or substantial morbidity. Please note: Based on Health Canada's' guidance the study phase is 'Other: Off‐Label use'. However, on the clincaltrial.gov record, 'Phase 4' is selected as this is the most relevant phase and there is no option to select 'Other'. Please note: McMaster University, Canada is the Canadian Regulatory Sponsor and Overall Sponsor, and the University of Adelaide Australia is the Australian Sponsor.

Nct (2021). "SOPHIE Trial: surgery in Ovarian Cancer With PreHabilitation In ERAS." ClinicalTrails.gov.
	Main objective: To determine the efficacy of multimodal prehabilitation in decreasing postoperative complications in patients undergoing gynecological cancer surgery of high complexity by laparotomy (primary cytoreductive surgery, interval surgery and secondary cytoreductive surgery in advanced ovarian cancer). Design: Multicenter randomized controlled clinical trial. Subjects: 146 patients: 73 in the intervention group and 73 in the control group. Intervention group: PreHAB intervention consists on: 1. High‐intensity endurance exercise training program and physical activity promotion remotely controlled with ICT (information and communications technologies). 2. Nutritional counselling to achieve protein intake of 1.5‐1.8 g/kg and whey protein supplements. 3. Psychological coping. Control group will receive standard preoperative care. Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. Measures: Aerobic capacity (incremental stress test), physical activity, operative complications and hospital length and associated costs.

Nct (2021). "Spherical Gelfoam Versus Tri-acryl Microsphere for Uterine Artery Embolization for Symptomatic Fibroids." ClinicalTrails.gov.
	Uterine artery embolization(UAE) is a minimally invasive treatment alternative to hysterectomy and myomectomy in symptomatic fibroids. However, post‐procedural pain after UAE remains a major problem. The spherical gelfoam and tri‐acryl gelatin microsphere are two embolic materials used for UAE. Therefore, the aim of study is to compare pain intensity and inflammation after uterine artery embolization using the two embolic agents with symptomatic fibroids.

Nct (2021). "A Study of AK104 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer." ClinicalTrails.gov.
	This is A Randomized, Double‐blind, Placebo‐controlled Phase III Study to Evaluate AK104 Plus Platinum‐containing Chemotherapy With or Without Bevacizumab as First‐line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer

Nct (2021). "A Study of Maintenance DCVAC/OvCa After First-line Chemotherapy Added Standard of Care." ClinicalTrails.gov.
	This is a randomized, double‐blind, placebo‐controlled,parallel‐group preliminary verifying study about safety and efficacy of maintenance DCVAC/OvCa after first‐line chemotherapy added to standard of care in patients with newly diagnosed FIGO III‐IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Nct (2021). "A Study of Navicixizumab in Patients With Platinum Resistant Ovarian Cancer." ClinicalTrails.gov.
	This is a Phase 3, randomized, open‐label, 2‐stage, multicenter study of navicixizumab with or without paclitaxel compared with paclitaxel monotherapy in patients with platinum‐resistant advanced epithelial ovarian cancer and specific biomarkers, as measured by the proprietary and validated Xerna™ TME Panel biomarker assay. Eligible patients must have received at least 2 prior regimens but not more than 5 prior regimens, including treatment with a monoclonal antibody angiogenesis inhibitor (e.g., bevacizumab), must be considered platinum‐resistant, and must be considered appropriate to receive single‐agent paclitaxel chemotherapy as a next line of therapy. All patients must be willing and able to provide a formalin‐fixed paraffin embedded (FFPE) archive or core tumor sample collected during screening for classification as B+ or B‐ biomarker status based on RNA expression data from the Xerna™ TME Panel biomarker assay. The co‐primary efficacy endpoints are ORR by RECIST v1.1 and PFS (as assessed by blinded independent radiological review [BIRR]) analyzed at different timepoints. Analysis of the ORR primary efficacy endpoints will occur at the end of Stage 1 and at the end of Stage 2; the PFS primary efficacy endpoint will be analyzed at the end of Stage 2. Patients will be stratified by Xerna™ TME Panel status and region and randomized to the following treatment arms according to the corresponding study stage randomization ratios. Enrollment will proceed from Stage 1 to Stage 2 without interruption: Stage 1 treatment arms (4:4:1 randomization): ‐ Combination navicixizumab + paclitaxel: navicixizumab 3 mg/kg once every 2 weeks (Q2W) of a 28‐day cycle (i.e., on Days 1 and 15); paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28‐day cycle ‐ Paclitaxel monotherapy: paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28‐day cycle ‐ Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28‐day cycle (i.e., on Days 1 and 15) • Stage 2 treatment arms (2:2:3 randomization): ‐ Combination navicixizumab + paclitaxel: navicixizumab 3 mg/kg Q2W of a 28‐day cycle (i.e., on Days 1 and 15); paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28‐day cycle ‐ Paclitaxel monotherapy: paclitaxel 80 mg/m2 on Days 1, 8 and 15 of a 28‐day cycle ‐ Navicixizumab monotherapy: navicixizumab 3 mg/kg Q2W of a 28‐day cycle (i.e., on Days 1 and 15) Within each treatment arm, patients will be stratified to a B+ or B‐ cohort based on their Xerna™ TME Panel biomarker assay results during screening. Patients in both stages will have radiologic tumor assessments every 8 weeks (±1 week), regardless of treatment delays, until objective disease progression, initiation of subsequent anticancer therapy, withdrawal of consent, death, or end of study, whichever occurs first. All patients will continue to receive study treatment until progressive disease (PD) per RECIST v1.1 (as assessed by the investigator), the development of unacceptable toxicity, withdrawal of consent, or another protocol‐defined discontinuation criteria is met, whichever occurs first, or until the sponsor terminates the study. Treatment decisions (i.e., whether to continue or discontinue the study medication) should not be made based on CA‐125 levels. Progression during protocol treatment cannot be declared on the basis of CA 125 alone. All patients who discontinue study treatment for any reason will be followed for survival at 3‐month intervals until death or withdrawal of consent, whichever occurs first. Survival follow‐up will continue for 12 months after the last patient is enrolled or approximately 75% of the population has died, whichever is later.

Nct (2021). "Study of Pant Type Absorbing Urinary Incontinence Products." ClinicalTrails.gov.
	The clinical clinical investigation is prospective, cross‐over, interventional, multicentre and pre‐market. The investigation aims to demonstrate the performance and safety of a new absorbing hygiene product (medical device) when used as intended in subjects affected with light to medium urinary incontinence compared to a reference (control) product representing standard of care. The study participants will be randomly assigned to one of 4 groups. Each group will receive a predefined pair of investigational and reference products (variants: either high waist or low waist) to be used in a predefined order (crossover design: investigational or reference product to be used first). Hence, each study subject will use two products (one investigational product and a corresponding reference product of the same variant) and act as its own control. The study subjects will use one product for 5 days and then switch to use the other product for 5 days. The primary endpoint for the investigation is the comparison in leakage performance of the investigation product with the reference product. There are also secondary endpoints regarding safety and product satisfaction and product preference.

Nct (2021). "A Study of SHR-1701 Plus Platinum-containing Chemotherapy With or Without BP102 (Bevacizumab) as First-line Treatment in Cervical Cancer." ClinicalTrails.gov.
	The study is being conducted to evaluate the efficacy, and safety of SHR‐1701 or Placebo Plus Chemotherapy With or Without BP102 (Bevacizumab) as First‐Line Treatment in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer.

Nct (2021). "Study of the Composition and Bacterial Diversity of the Vaginal Microbiota in Healthy Versus Pathological Conditions (Bacterial Vaginosis) Using a Targeted Metagenomic Approach (RNA 16s)." ClinicalTrails.gov.
	It aims to determine and compare the degree of vaginal bacterial alpha diversity in the absence (healthy population) or presence of bacterial vaginosis (pathological population).

Nct (2021). "A Study to Learn How Safe Elinzanetant is, How it Affects the Body, and How it Moves Into, Through and Out of the Body After Single and Multiple Doses in Japanese Healthy Female Adults." ClinicalTrails.gov.
	Researchers are looking for a new way to treat women who have symptoms that are caused by the sex hormonal changes that happen when a woman's body is going through the menopause. These symptoms include Vasomotor Symptoms (VMS) (hot flashes), and changes in blood pressure. Menopause is when women stop having a menstrual cycle, also called a period. During the period, the ovaries increasingly produce less sex hormones as a result of the natural ageing process and related hormonal adjustments. The decline in hormone production can lead to various symptoms which, in some cases, can have a very adverse effect on a menopausal woman's quality of life. In this study, researchers want to learn more about a new substance called elinzanetant. Elinzanetant was developed to treat symptoms caused by sex hormonal changes. It works by blocking a group of proteins called neurokinins from sending signals to other parts of the body, which play a role in starting the symptoms. In this study, the researchers will learn how safe elinzanetant is and how it affects the body of healthy Japanese women compared to a placebo. A placebo is a treatment that looks like a medicine but does not have any medicine in it. Before a new treatment can be given to patients, researchers do studies in healthy participants to learn more about its safety and how it acts in the body. There will be 2 parts to this study. In Part A, the participants will take a single dose of either elinzanetant or the placebo. In Part B, the participants will take multiple doses of elinzanetant or the placebo. The participants will take each study treatment as capsules by mouth. The main purpose of this study is to learn how safe elinzanetant is and how it affects the body. To answer this question, the researchers will collect the medical problems the participants have after receiving the treatment and that may or may not be related to the study treatment. These medical problems are also known as "adverse events". During Part A, the participants will stay at their study site for a total of 9 days. They will take either elinzanetant or the placebo only on Day 1 of their stay. During Part B, the participants will stay at their study site for a total of 15 days. They will take either elinzanetant or the placebo once a day for 7 days of their stay. Each participant will be in the study for a total of approximately 5 weeks for Part A and approximately 6 weeks for Part B. During the study, the doctors will: ‐ take blood and urine samples; ‐ check the participants' health; ‐ ask the participants questions about what medicines they are taking and if they are having adverse events.

Nct (2021). "Sublingual Misoprostol In Medical Treatment of First Trimester Missed Miscarriage." ClinicalTrails.gov.
	the study will be made on female patients with the first trimester missed abortion confirmed by ultrasound. Participants will be divided into 2 groups one group (A) will receive sublingual Misoprostol 400 mcg and the other group(B) will receive sublingual Misoprostol 800 mcg every 4 hours in both groups up to 3 doses the aim of the study is to compare the efficacy of sublingual Misoprostol in complete termination of the first trimester missed abortion and which route is the best will less side effects.

Nct (2021). "Swedish Rectal Prolapse Trial." ClinicalTrails.gov.
	Background Full thickness rectal prolapse, or procidentia, is a benign but distressing condition. It is defined as the circumferential protrusion of all layers of the rectal wall through the anal sphincters. The annual incidence is 2,5 per 100 000, predominantly in the elderly, and male‐to‐female ratio is about 1:6. More than 100 different procedures have been described for surgical treatment of rectal prolapse and consensus has not yet been reached. Traditionally, perineal procedures have been reserved for older patients who are not fit for an abdominal operation. The two most common perineal procedures are Delorme's operation, i.e. mucosectomy and rectal plication, and perineal rectosigmoidectomy, also known as Altemeier's operation, which is a full‐thickness excision of the rectum. The choices between abdominal vs. perineal approach and resection or not were all addressed in the Swedish rectal prolapse trial with possible differences in bowel function, quality of life, recurrence rate and complications as end points. Study design and randomization This was a multicenter randomized trial with a 2 x 2 factorial design conducted in 13 sites in Sweden. At inclusion, patients signed an informed consent form and the attending surgeon contacted the central trial office at the Danderyd Hospital, Stockholm, Sweden. Randomization was performed with randomly assigned envelopes, stratified for each participating center. Patients were randomized between perineal and abdominal approach (A). The perineal group was further randomized to Delorme's or Altemeier's procedure (B) and the abdominal group to suture rectopexy or resection rectopexy (C). Patients who were considered unsuitable for random allocation to a perineal or an abdominal procedure were included only in (B) or (C). Preoperative evaluation and procedures All patients were clinically examined and diagnosed with full thickness rectal prolapse. Further examinations with endoscopy, colon transit studies, anorectal manometry, defecography, endoanal ultrasound and pudendal nerve motor latency were optional and were performed as indicated at each surgeon's discretion. Operative procedures were described in the study protocol, see appendix. Abdominal procedures were performed laparoscopically or as open procedure. In order to validate data all questionnaires were gathered at the central trial hospital and inspected by a second researcher. The surgical procedures were identified and standardized to a large extent. Both minimal invasive and open surgery were allowed. For example the abdominal procedures were described that mobilization of rectum should be done in the posterior aspect, the lateral ligaments should not be divided, Suture rectopexy should be done with non‐absorbable 0.0 sutures, the cul de sac should not be closed. The sample size was calculated to 220 patients in the first randomization between abdominal and perineal approach. With 220 patients a difference in recurrence of 13% could be identified with 90% power in a significance level of 5%. The plan was to analyze the categorical variables with either Fisher´s exact test or multivariate analysis. A main study office was situated at Danderyd Hospital and randomization was done from this office at the time when the patient was scheduled for surgery. All hospitals performing surgery for rectal prolapses in Sweden were invited to the study.

Nct (2021). "Tackling Postnatal Depression: culturally Adapted Learning Through Play Plus (LTP+) Intervention for British Mothers of African and Caribbean Origin." ClinicalTrails.gov.
	By 2030, depression will be the leading global disease burden. Postnatal depression due to childbirth/parenting leads to long‐term negative consequences for mothers, their children and their families. The British African/Caribbean communities are worse hit by the unprecedented impact of post‐Covid‐19‐syndromes, leading to an exponential increase in postnatal depression. Yet, the uptake of mental healthcare by British mothers of African and Caribbean origin is low due to limited access to culturally appropriate care. Theories of attachment and cognitivism were innovatively integrated to examine Learning‐Through‐Play plus (LTP+) intervention for postnatal depression using a pilot randomised controlled trial. The proposed LTP+ is co‐developed and ecologically friendly because it is manualised and can be delivered by non‐mental health specialists such as trained community health workers who are more culturally knowledgeable. Findings will be disseminated through academic publications/presentations, policy briefs, original animated videos and podcast series laying the foundations for a psychosocial approach to tackling postnatal depression

Nct (2021). "Tailoring Online Continence Promotion." ClinicalTrails.gov.
	The investigators will conduct a two‐arm, parallel, randomized, controlled trial (RCT) comparing an online continence promotion program with standard weekly reminders (control arm) to an online continence promotion program with tailoring (treatment arm) to determine the impact of tailoring on program engagement. Women in the treatment arm will receive tailored content and digital reminders for 24 weeks based on their individual characteristics, symptoms, and behaviors assessed at baseline, with reassessment of key inputs every 2 weeks resulting in re‐tailored outputs. Participants will complete electronic surveys at enrollment, 4, 12, and 24 weeks. To contextualize the findings from all 3 aims, a subset of participants will be invited to complete semi‐structured qualitative interviews about their engagement with the program, their adoption of health behaviors, and their perceived barriers to and facilitators of engagement and behavior change.

Nct (2021). "TEST-ON - Does iStim Reduce Urinary Urgency?" ClinicalTrails.gov.
	This will be a prospective randomized cross over trial. We will recruit women who present to clinic to see a Female Pelvic Medicine and Reconstructive Surgery, fellowship‐trained provider within the UCLA Health System with the symptoms of OAB‐dry and have failed or decline anti‐cholinergic therapy. Screening: Patients will be made aware of the study by their physician. Interested subjects will interact with study staff in person or by telephone for a complete description of the study. If they wish to continue, they will be screened for eligibility by study staff. If eligible, they will be given as much time as they wish to complete the process of informed consent and have their questions answered. Consent will be obtained electronically using the RedCap system. After informed consent, subjects will be asked to complete intake questionnaires, sent through the RedCap site. These questionnaires include the International Consultation on Incontinence Questionnaire‐Female Lower Urinary Tract Symptoms (ICIQ‐FLUTS), female GenitoUrinary Pain Index (fGUPI), Pelvic Organ Prolapse Distress Inventory (POPDI‐6) portion of the Pelvic Floor Disability Index (PFDI), the first 8 questions of the OverActive Bladder questionnaire (OAB‐q), the last question of the AUA symptom score, and the Urgency Perception Scale: UPC. After informed consent, study staff will access subjects' medical records to obtain the results of standard care procedures that are regularly performed for patients with this symptomatology, specifically, pelvic exam and urodynamics. Participants will be asked to make a research visit for training and to obtain materials. They will be issued the iStim device. Both groups will be oriented to the vaginal stimulation device which includes the iStim TENS unit and Transvaginal Probe. The iStim TENS unit delivers a bipolar square wave that can be delivered over a range of 0 to 100 mA. On the TENS unit the patient can set frequency, duration of stimulation, pulse duration, and amplitude. During each participant's in‐person visit they will be instructed by trained study staff on how to use the electrical stimulation. Patients will be randomized to treatment A followed by treatment B (Group 1) or treatment B followed by treatment A (Group 2). The patients will be blinded to which treatment they are receiving first. Each treatment phase will be 4 weeks in duration. The washout period between phases will be three weeks. Patients will be given a log to record each session completed at home in order to determine compliance. They will also be asked to record the amplitude achieved for each session in the treatment phase. Patients will be able to report adverse events electronically through RedCap or by contacting study staff directly. At the end of each 4‐week treatment patients will be asked to complete the same intake questionnaires again with the addition of the select questions from the modified version of the Overactive Bladder Patient Satisfaction with Treatment Questionnaire (OAB‐PSTQ) and Patient Global Assessment (PGA) which assesses their perception of the intervention. At the end of the intervention, participants will be asked to complete a bladder diary again using the same IUGA bladder diary. Participants will be followed through their medical record for 6 months after completion of study activities. Further OAB therapies tried will be recorded as well as pelvic exams and/or urodynamics done as part of their standard care. They will be asked to complete the set of intake questionnaires once more at the end of 6 months.

Nct (2021). "Therapeutic Touch and Music in The Menopausal Period." ClinicalTrails.gov.
	Menopause is a long period of life characterized by the permanent termination of the menstrual cycle due to the cessation of ovarian functions. It is the most important midlife crisis in which special physical and psychological differences occur, often associated with a decrease in estrogen levels. Although the natural age of menopause varies, it usually ranges from 40 to 58 years, and the average age of menopause is accepted as 51. When the average life expectancy of women is accepted as 80 years, women spend about a third or more of their life in the postmenopausal period. Along with the decrease in estrogen during menopause, symptoms related to hot flashes, night sweats, palpitations, irritability and sleep disorders are common. Especially sleep disorders are higher than in the premenopausal period. It has been reported that approximately 40‐60% of menopausal women have sleep‐related symptoms with night awakenings as the most common complaint. In the study of Lima et al. in which they included 819 climacteric women in Brazil; Deterioration in sleep quality was detected in 67% of the sample, more prominently in postmenopausal women. The most common complaints during menopause are deterioration of sleep quality and chronic insomnia. Untreated sleep disorders and menopausal symptoms adversely affect health and especially reduce quality of life. When the literature is examined, poor sleep quality and insufficient sleep duration; hormonal changes, poor physical health, obesity, cardiovascular disease, diabetes, irritability, physical and mental burnout, and poor quality of life, such as short‐term and long‐term outcomes. It is stated that the symptoms seen in the menopausal period negatively affect the quality of life of women. Although the effective treatment to be used to solve the sleep problems experienced during the menopause period, reduce the menopausal symptoms and improve the quality of life is medication or hormonal therapy, the use of non‐pharmacological methods is increasing due to the potential side effects of these treatments and the harm outweighing the benefit. Some of these methods are music, yoga, aromatherapy, therapeutic massage, physical exercise, sleep hygiene education, therapeutic touch, acupressure, acupuncture and cognitive behavioral therapy methods. Therapeutic touch, which is among the non‐pharmacological methods that have started to be preferred in recent years, is the interpretation of an ancient healing experience in the modern age. It is a non‐invasive nursing intervention that channels energy using the hands. There are no known side effects associated with the use of therapeutic touch. Therapeutic touch is beneficial in reducing anxiety, pain and depression, and increasing relaxation and well‐being.Therefore, this calming effect of therapeutic touch also facilitates falling asleep and can improve quality of life by easing menopausal symptoms. Another widely used non‐pharmacological method is recital. Perceived calming music lowers catecholamine levels, respiratory rate, heart rate, and blood pressure. Therefore, by roviding physiological and psychological relaxation, music helps individuals to sleep better, reduce menopausal symptoms, and improve quality of life. In a meta analysis study, it was determined that listening to calming music effectively improved sleep quality. When the literature was examined, no study was found that examined the effects of therapeutic touch and music listening on sleep quality, menopausal symptoms and menopausal quality of life in menopausal women. It is thought that the findings obtained from the research will contribute to the literature. Based on all these, the aim of this study is to examine the effects of therapeutic touch and music listening on sleep quality, menopausal symptoms and quality of life in menopausal women. Purpose Of The Study The aim of the study was to investigate the effect of therapeutic touch and music listening on sleep quality, menopausal symptoms and quality of life in menopausal women. Research Hypotheses H : Therapeutic touch does not affect sleep quality in menopausal women H11: Therapeutic touch affects sleep quality in menopausal women H20: Therapeutic touch does not affect menopausal symptoms in menopausal women H21: Therapeutic touch affects menopausal symptoms in menopausal women H30: Therapeutic touch does not affect quality of life in menopausal women H31: Therapeutic touch affects quality of life in menopausal women H40: Music listening does not affect sleep quality in menopausal women H41: Listening to music affects sleep quality in menopausal women H50: Listening to music does not affect menopausal symptoms in menopausal women H51: Listening to music affects menopausal symptoms in menopausal women H60: Music listening does not affect quality of life in menopausal women H61: Music listening affects quality of life in menopausal women

Nct (2021). "Time Restricted Eating (TRE) Among Endometrial Cancer Patients." ClinicalTrails.gov.
	Enrollment: The study team will aim to recruit 15 endometrial cancer patients seen at the Huntsman Cancer Hospital Clinics. Consent may be completed via phone/email or in‐person with the study clinical coordinator. Dietary Intervention: Participants who are consented into the study will participate in a 16‐week randomized dietary crossover intervention. The dietary intervention includes 5 study visits, and features a baseline visit, 2‐week run‐in period, 4‐week control diet schedule with prepared frozen meals provided to participants, 4‐week washout period, and a 6‐week, 8 to 10‐hour Time Restricted Eating (TRE) protocol (meal provision with 8 to 10‐hour eating and 14 to 16‐hour fasting periods). Women will be randomized to either control or TRE, then crossover to the other condition. For the control schedule, women will receive frozen lunch and dinner meals and be provided with a standardized breakfast and snacks menu, and there are no restrictions on timing of eating. For the TRE schedule, women will receive prepared frozen lunch and dinner meals as per the control schedule, but will be asked to consume daily meals, snacks, and calorie‐containing beverages within an 8 to 10‐hour period that fits their schedule. Fasting period will ramp up during the first week (e.g., Days 1‐3, 12‐14 h per day, Days 4‐6, 14‐16 h per day, Days 7+, 16 h per day). Women will be asked to schedule the eating period at the same time each day. Study Visits and Assessments: Women will attend in‐person study visits at the Huntsman Cancer Institute Center for Health Outcomes and Population Equity (HOPE). ‐ Baseline Visit (Visit 1): The clinical coordinator will obtain consent from the participant. Once consented, women will complete questionnaires to capture information on clinical and demographic factors, and chronotype. Height will be measured using stadiometer, weight will be measured using calibrated scales, waist circumference with measuring tape and blood pressure (BP) using an electronic BP monitor. Participants may take home questionnaires, with mailer, to complete at home. ‐ 2‐Week Run‐In Period: The purpose of the run‐in period is to record women's usual times of eating episodes and appetite while following their habitual diet. Appetite will be measured using the MyCircacianClock (mCC) phone app that has the capability to sample subjects' current behaviors and experiences in real time in their natural environment. Women will complete 3 x 24‐hour dietary recalls on non‐consecutive days (ASA‐24) and a physical activity recall (ACT24 available online or phone app, or via telephone conference with the clinical coordinator). Sleep and activity will also be objectively measured for 7‐days using an Actiwatch. ‐ Visit 2: Women will provide fasting blood and stool samples. Weight, waist circumference and blood pressure will be measured. ‐ Control OR TRE Schedules: The participants will be expected to follow their randomized schedule for meal timing. During these schedules, for both study groups, participants will record timing of eating episodes daily using the MyCircadianClock app, complete 3 x 24‐hour recalls (ASA24), 1 x ACT24 activity recall, and 7‐days of sleep/physical activity will be objectively measured via Actiwatch. ‐ Visit 3: Women will provide fasting blood and stool samples. Weight, waist circumference and blood pressure will be measured. ‐ 4‐Week Washout Period: During the washout period, women can return to their usual lifestyle. Meals will not be provided during this time. ‐ Visit 4: Visit 4 will include a telephone call only to discuss the next study phase and schedule meal provision. ‐ Visit 5: Women will provide fasting blood and stool samples. Weight, waist circumference and blood pressure will be measured. An exit interview may occur in person or via phone/video conference to ask questions about how well the intervention was tolerated and allow participants to provide feedback. ‐ Follow‐Up: Approximately 6‐months after consent and roughly 10 e ks after the end of the dietary intervention, participants will be asked to complete a follow‐up questionnaire.

Nct (2021). "Time Restricted Eating (TRE) Among Native Hawaiian/Pacific Islander Women at Risk for Endometrial Cancer." ClinicalTrails.gov.
	Enrollment: The study includes two phases. Phase 1 includes focus groups among 30 Native Hawaiian/Pacific Islander women at risk of endometrial cancer. Focus groups will determine sociocultural influences on (i) dietary behavior including meal timing; (ii) dietary preferences; (iii) proposed meal plans and intervention design; (iv) perceptions of weight loss and body image. In the second study phase, the study team will recruit 10 Pacific Islander women to participate in a 14‐week randomized dietary crossover study. Each woman will participate in both intervention arms and act as her own control. Focus Group: To accomplish all aspects of Aim 1 of this study, the study team will recruit 30 Pacific Islander women at risk for endometrial cancer to conduct virtual focus groups. These focus groups will take place via private videoconference, like Zoom, and a language translator will be provided, as necessary. The focus groups will be attended by a Native Hawaiian/Pacific Islander Community Expert. Questions will be designed to understand sociocultural influences on dietary behavior (questions on social eating, meal timing, and dietary preferences, soliciting feedback on study intervention delivery design, and perceptions of weight loss and body image). An icebreaker will be conducted prior to formal questioning. Sessions will be audio‐recorded on the videoconference and an additional device, transcribed verbatim, and checked for accuracy. Two additional team members will be present as note takers. Our Community Expert will be present to help facilitate the session. Questions will be provided at the beginning of the session to ensure cultural sensitivity. Dietary Intervention: The dietary intervention includes 5 study visits, and features a baseline visit, 2‐week run‐in period, 4‐week control diet schedule, 4‐week washout period, and a 4‐week, 8 to 10‐hour Time Restricted Eating (TRE) protocol (8 to 10‐hour feeding and 14 to 16‐hour fasting periods). A follow‐up questionnaire will be mailed 6‐months post‐ intervention. For the control schedule, women will receive frozen lunch and dinner meals and a standardized breakfast and snacks menu. All meals and the breakfast/snack menu will be designed to be culturally competent with feedback from the focus groups, and meal plans will be individualized to meet weight maintenance energy requirements. For the TRE schedule, women will receive prepared frozen lunch and dinner meals as per the control schedule, but will be asked to consume daily meals, snacks, and calorie‐containing beverages within an 8 to 10‐hour period that fits their schedule. They will be asked to maintain their regular sleep and physical activity schedule. The fasting period will ramp up during the first week (Days 1‐3, 12‐14 h per day, Days 4‐6, 14‐16 h per day, Days 7+, 16 h per day). Women will be asked to schedule the eating period at the same time each day. All meals (control and TRE) will be provided by the Metabolic Kitchen located at the University of Utah. Visit 1: During the baseline visit, a coordinator will obtain consent from the participant, and they will be asked to compete questionnaires asking about clinical and demographic factors, chronotype, and physical activity, and various anthropometric measurements will be taken. Following the baseline visit, participants will undergo a 2‐week run‐in period. During this time, the goal is to record women's usual times of eating episodes and appetite while following their habitual diet. Visit 2: Women will provide fasting blood and stool samples, and anthropometric measurements will be taken. Following visit 2, participants will undergo the control or TRE schedule for 4 weeks. Visit 3: After 4 weeks, participants will undergo visit 3 and will be asked to provide fasting blood and stool samples, and anthropometric measures will be taken. Following visit 3, participants will undergo a 4‐week washout period, where women are able to return to their usual lifestyle. Visit 4: Visit 4 will occur after the 4‐week washo period, and will include a telephone consultation to discuss the next study phase and schedule meal provision. For the following 4‐weeks, participants will then undergo the opposite feeding schedule (either control or TRE). Visit 5: During the final visit, women will provide fasting blood and stool samples, and anthropometric measures will be taken. During the run‐in period, the TRE phase and the control phase, participants will record timing of eating episodes using the MyCircadian Clock phone app, complete 3 x 24‐hour diet recalls, a single physical activity recall, and 7‐days of sleep and physical activity will be objectively measured using an Actiwatch device. Hunger and satiety will be evaluated at random through the MyCircadian Clock phone app. A study exit interview will be conducted via Zoom conference call to debrief on the intervention and obtain detailed information on acceptability of the protocol. Approximately 6‐months after the end of the intervention period, women will complete a mailed follow‐up questionnaire.

Nct (2021). "Time-restricted Eating to Improve Metabolic Abnormalities in Polycystic Ovarian Syndrome." ClinicalTrails.gov.
	Background: Polycystic ovarian syndrome (PCOS) is the most common reproductive endocrinopathy in women of reproductive age with many associated metabolic symptoms, in particular hyperinsulinemia, insulin resistance and a high lifetime risk of type 2 diabetes mellitus. The effects of time‐restricted eating on metabolic profiles have been investigated in many endocrinopathies, but there are minimal data in PCOS. Methods: This study will investigate the feasibility of time‐restricted eating in the management of PCOS, and its effects on insulin levels and other metabolic parameters. To achieve this, the investigators will recruit 20 patients with PCOS (normal weight, overweight, obese). In a randomised cross‐over design, participants will be observed for two consecutive 12 week periods (with a 4 weeks washout period in between) following either 'time‐restricted eating' or 'usual eating', detailed below. 1. 18:6 protocol: 18 hours of fasting and a 6‐hours eating window, with no other specific dietary advice. Participants choose their own 6‐hour period according to their lifestyle and preference. 2. Usual eating: follow usual eating patterns, no time restriction, no other dietary advice When fasting, participants are permitted to consume plain water, unflavoured/unsweetened sparkling water, black breakfast tea and black coffee. Dietary intake will be determined at baseline, at midpoint of each study arm, and at the end of the study using Nutritics software. Participants will self‐record dietary intake using the Nutritics 'app'. The primary endpoints will be serum insulin and feasibility of the intervention as well as safety, acceptability, and compliance with time‐restricted eating. Secondary endpoints will be insulin resistance (Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR)), androgens (testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA‐S), androstenedione, 17‐Hydroxyprogesterone (17‐OHP) and sex hormone binding globulin (SHBG)), appetite (10‐point visual analogue scale), hunger/satiety (glucagon‐like peptide 1 (GLP‐1), grehlin, PYY and oxyntomodulin, fasting glucose, HbA1c, lipid profile, lipoprotein lipid A, apolipoprotein A1, apolipoprotein B, anthropometrics (weight, body mass index, hip and waist circumference), dietary intake (calorie and macronutrient intake; micronutrient intake including iron, calcium; dietary pattern including timing). Results: Safety and acceptability will be measured by adverse event reporting and measurement of adherence. Paired t‐test will be used to assess between baseline and post intervention measurements. Results considered statistically significant if p<0.05. Discussion: Time‐restricted eating has potential to aid in improvement of insulin resistance in patients with PCOS based on studies in other populations. There is no substantial literature on this subject to date in the PCOS patient cohort, with this being the first randomised study to date. The investigators will discuss the effects of time‐restricted eating on insulin levels in the specific population of women with PCOS based on the results.

Nct (2021). "To Assess Signs and Symptoms in Women Affected by GSM After One Cycle of Pixel CO2-Alma Fractionated Laser." ClinicalTrails.gov.
	Genitourinary syndrome of menopause (GSM) occurs in approximately 50% of menopausal women but is both underrecognized and undertreated despite numerous treatment options. Vaginal dryness, irritation, dyspareunia, urinary frequency, and urinary urgency are some of the more common symptoms that can have a negative effect on women's lives and relationships. In particular, dyspareunia is localized in the vestibule with specific trophic changes more evident than those localized in vagina. The CO2 fractionated laser, has also been found to be useful in several studies for the treatment of vaginal atrophy. In this open comparative study, 70 female menopausal subjects aged between 40 and 70 years old at inclusion, having symptoms of GSM (Vaginal dryness, burning/pain, dyspareunia,dysuria), have given her informed consent and meet all the eligibility criteria, will be enrolled. The two groups of comparison will be 35 subjects treated into vagina and vestibule, versus 35 subjects treated into vagina, only. Subjects will come to a total of 6 visits over a period of 3 months. The primary objective of the study is to evaluate the performance and safety of Pixel CO2‐Alma Fractionated Laser comparing its administration into vagina and vestibule versus into vagina, only. The evaluated outcomes are vaginal dryness, burning/pain, dyspareunia, sensitivity to touch at Swab test, Female Sexual Function Index (FSFI) and Vulval Pain Functional Questionnaire (VQ) at day 84 and 120 and the safety during all the study. The secondary objectives are the evaluation of vaginal and vestibular trophism, measured by Vaginal Health Index (VHI) and Vestibular Health Score (VHS) at the FU visits.

Nct (2021). "To Evaluate the Effectiveness of a Virtual and Telephone Intervention for the Prevention of Postpartum Depression in Women at Risk." ClinicalTrails.gov.
	The Parents & Babies intervention to be evaluated is an adaptation of the existing, evidence‐based Mothers & Babies program which has shown efficacy in four clinical trials for the prevention of postpartum depression through in‐person (group or individual) counseling The Parents & Babies program was adapted to be virtual and include: 1) specific modules for the mother‐partner dyad; 2) third‐wave cognitive behavioral therapy (CBT) strategies targeting well‐being, relaxation, mindfulness, self‐compassion, and gratitude; 3) confinement and social distancing related material. Participants follow the program online or with a paper workbook and are called weekly by a member of the intervention team. Participants will fill out three questionnaires (online or by telephone) at 12‐25 weeks' gestation, 3 months' postpartum and 6‐months postpartum to assess baseline values and trial outcomes, respectively.

Nct (2021). "To Evaluate the Efficacy and Safety of JLP-2002 on Symptoms of Overactive Bladder." ClinicalTrails.gov.
	Overactive bladder (OAB) is a clinical condition characterized by urgency (i.e., urinary urinary urinary urgency that is difficult to delay and unbearable) with or without urge incontinence, usually associated with frequency and nocturia. The main drug class used is antimuscarinics, and the clinical utility of antimuscarinic drugs is limited due to its mild efficacy and poor tolerability due to side effects of mechanisms such as dry mouth and constipation. In addition to poor tolerability and mild efficacy, recent literature suggests that long‐term use of anticholinergics is associated with cognitive impairment and dementia. Therefore, the purpose of this study was to evaluate the treatment effect of overactive bladder symptoms through the change in the average number of urination per day after administration of JLP‐2002, a beta 3‐adrenergic receptor (β3‐AR) agonist with an effective alternative mechanism, for 12 weeks.

Nct (2021). "Topical Tranexamic Acid for the Prevention of Postpartum Hemorrhage in Women Undergoing Elective Cesarean Section." ClinicalTrails.gov.
	patients were allocated to one of two groups after induction of anesthesia. they received temporary uterine packing with gauze of the dimensions soaked with 2 gm tranexamic diluted in 60ml saline acid or placebo

Nct (2021). "Treatment of Cervical Intraepithelial Neoplasia (CIN) Grade III With Non-invasive Physical Plasma." ClinicalTrails.gov.
	Cervical intraepithelial neoplasms (CIN), classified into severity levels CIN I to III, can be precursors to cervical cancer (CC), the world's third most common cancer in women (270,000 deaths / year), which radical therapies are often associated with lifelong severe physical and emotional stress. Cross‐sectional studies found a prevalence for CIN of 62 per 1,000 women and incidences of 1.2 (CIN I), 0.8 (CIN II) and 0.7 (CIN III) per 1,000 women per year (highest incidence of CIN between 20 and 24 years) age). The standard therapy for the treatment of CIN III by LEEP excision is associated with an increase in mortality of 17%. CIN III, in particular, is associated with a significant decline in quality of life, psychological well‐being and sexual health, although on average only about 12% of CIN III lesions progress to invasive CC. The resulting over‐treatment (in around 8‐9 out of 10 patients) with invasive procedures is a serious problem for affected women, health care providers and the health economy. The NIPP treatment is a tissue‐sparing, pain‐free, easy to carry out and outpatient treatment method without anesthesia and hospitalization. A non‐randomized, one‐arm feasibility study at the Department of Women's Health (649 / 2017BO1) already showed the effectiveness of a NIPP treatment. Clinical implications for CIN III: ‐ A previous NIPP treatment should significantly reduce the invasiveness of the LEEP excision. ‐ If the oncological safety of NIPP treatment is comparable (histological complete remission of CIN III), NIPP is to be established as a safe alternative to LEEP excision in the future.

Nct (2021). "A Trial of Sublingual Misoprostol to Reduce Primary Postpartum Haemorrhage After Vaginal Delivery." ClinicalTrails.gov.
	The investigators propose a multi‐center randomized controlled trial. All women eligible for the trial will be recruited at antenatal clinic or antenatal ward. Women with risk factors for PPH and who are planning for Caesarean delivery will be excluded. Women are informed of the study in the antenatal clinic between 36 to 40 weeks gestation. An information sheet will be distributed and a written consent will be obtained. This trial will involve three maternity units in Hospital Authority (Queen Mary Hospital, Queen Elizabeth Hospital and Pamela Youde Nethersole Eastern Hospital) with total annual delivery of 11673 in 2018. Among the annual delivery of 11000, 70% would be vaginal delivery and 60% of women with vaginal delivery would be at low risk for PPH, about 4600 women per year will be eligible in the three units. The investigators aim to recruit 400‐500 women per year in total in the three units and the sample size is 1300 women in total over three years. Eligible women will be randomly assigned in a 1:1 ratio by a computer‐generated list to misoprostol or control group when the women are in active labour. Women in misoprostol group will receive sublingual misoprostol 600 micrograms in addition to routine uterotonics, whereas women in control group will receive routine uterotonics. Central randomization will be performed, generated by stratified block randomization, stratified by individual centers. Randomization will be performed when women are in advanced labour i.e. cervical dilatation at 8cm or more and will be stratified by centres and parity (nulliparous vs multiparous). Antenatal and intrapartum care of the women will follow routine care. A blood sample for complete blood count will be taken when women are admitted in labour. Active management of third stage of labour will be provided as routine postpartum care (including use of routine uterotonics and controlled cord traction). Delayed cord clamping is allowed at discretion of managing clinicians. Studies have shown the delayed cord clamping is beneficial to newborn and it does not increase risk of maternal bleeding. At delivery of baby, routine uterotonics (syntometrine 1ml intramuscular or syntocinon 5 units intravenous bolus followed by 40 units in 500ml normal saline infusion over 4 hours in women contraindicated for syntometrine) will be given as routine practice, and sublingual misoprostol will be given to women in misoprostol group. Blood loss will be measured during vaginal delivery by direct collection of blood with a calibrated obstetric drape. The calibrated under‐buttock drape folds out into a 1x1 meter sterile surface for delivery. The device allows for blood to be collected into a transparent calibrated pouch with capacity up to 2500ml. There are markings on the pouch that aid blood volume measurement. Immediately after delivery of baby and before delivery of placenta, amniotic fluid will be drained and a surgical drape with a graduated bag will be placed under women's buttock to collect the blood loss. The bag will remain in place for at least 15 minutes and until the birth attendants consider that the bleeding has stopped. Swabs and drapes soaked with blood will be weighed using a standardized scale for blood loss calculation (subtracting the known dry weight of the drapes and swabs) in addition to that collected in the graduated bag. Clinicians who assess the blood loss will be blinded to study group allocation. Maternal blood pressure, pulse and temperature will be recorded every 4 hours for one day after delivery. An observation form will be used to record maternal side effects. Blood will be checked for complete blood count on day 2 after delivery. In order to standardize various study procedures, training will be provided at individual study sites by investigators. Training will include recruitment procedure, randomization , administration of study drug and blood loss measurement method. Research assistant will have regular visit in various study sites to check consistency of the above procedures. Investigators will have re lar communication and meetings with co‐investigators at the study sites to review study procedures and to review study progress and address potential problems arising from the study.

Nct (2021). "TUC3PII-01_TU2670 Phase IIa Clinical Study." ClinicalTrails.gov.
	Treatment Groups and Duration: Following a washout period of up to 12 weeks, subjects will enter a screening period of up to 12 weeks including an observation period consisting of a complete menstrual cycle. Subjects will be randomly assigned in a 1:1:1:1 ratio to receive either 12 weeks of TU2670 320 mg QD, TU2670 240 mg QD, TU2670 120 mg QD, or matching placebo. TU2670 or a matching placebo will be administered in the clinic on Day 1. Subjects in the PK subset population will also receive the following additional doses in the clinic: Day 2 (after collection of the 24‐hour PK sample); the dose on the day scheduled for subsequent serial PK sample collection (Week 4 or Week 5); and the next scheduled dose (after collection of the 24‐hour PK sample). All other doses can be taken by the subject at home. Following the end of treatment, subjects will be followed up for safety for 12 weeks. Statistical Methods: All formal statistical tests will be done at the 5% 2‐sided significance level. Point estimates will have 2 sided 95% confidence intervals (CIs) where applicable. Where appropriate, variables will be summarized descriptively (frequency and percent will be summarized for categorical variables; n (number of available subjects), mean, standard deviation [SD], median, minimum, and maximum will be presented for continuous variables) by study visit and by treatment group. Statistical summaries will be presented for the changes from baseline to each time point in efficacy endpoints that it is applicable.

Nct (2021). "UA Versus UAE in Treatment of Fibroids." ClinicalTrails.gov.
	Inclusion Criteria: Women with symptomatic uterine fibroids were recruited into the study after fulfilling the following criteria: ‐ Their age should range from 35 to 50 years. ‐ Their body mass index (BMI) should range from 18 to 35 Kg/m2. ‐ The presence of multiple symptomatic type 2, 3, 4, 5, or 6 uterine fibroids according to the FIGO classification. ‐ The dominant fibroid diameter should range from 4 to 8 cm as assessed by ultrasound. ‐ They should not be seeking future fertility. ‐ They should be refusing any surgical intervention whether myomectomy or hysterectomy. Exclusion Criteria: 1. Post‐menopausal status or premature ovarian failure. 2. Type 0, 1 and 7 uterine fibroids according to FIGO classification. 3. Previous myomectomy or any uterine surgery. 4. Previous or ongoing hormonal treatment. Sampling Method: The study sample will be a "convenient sample" where women fulfilling the inclusion criteria and consenting to participate in the study will be recruited. Sample Size justification: The study will include 70 women with symptomatic uterine fibroids who will be randomized into two groups with 35 women in each group. The required sample size has been calculated using the PASS 15 Power Anal‐ysis and Sample Size Software (PASS©) version 15 (2017); NCSS, LLC. Kaysville, Utah, USA. The main outcome measure is the reduction in fibroid volume. The secondary outcome measures are symptoms relief and improvement in quality of life. A previous study reported that Ulipristal Acetate (UA) was comparable to uterine artery embolization (UAE) as regards the percentage of reduction in fibroid volume with median (interquartile range) percentage reduction of 48.1 (24.8 ‐ 66) % versus 47.3 (29.5 ‐ 69.5) % for UPA and UAE respectively (Czuczwar et al., 2015). Using the methods described by Wan et al (2014) and Luo et al (2018), we calculated that the mean ± SD percentage of reduction in fibroid volume was 44.0 ± 28.5 % versus 48.9 ±32.3 % for UPA and UAE respectively, with mean difference of 4.9 % and common within group SD of 30.5%. Taking into consideration a "drop‐out rate" of about 10%, due to loss of follow up or withdrawal from the study, it is estimated that a sample size of 35 patients per group achieves 80% power using a one‐sided equivalence test with a significance level of 5% (alpha‐error = 0.05), when the difference between the two means is 4.9 %, common within group SD is 30.5 %, and equivalence limits are ‐25% and 25%. On the other hand, this sample size achieves a power of 82% to detect a statistically significant difference between the two groups as regards the symptoms scores and measures of ovarian reserve (AFC and AMH) for an effect size equivalent to a Cohen's d of 0.75 (i.e., 0.75 common SD) using a two‐sided unpaired t‐test with the same significance level of alpha = 0.05. These equivalence limits and effect size have been targeted, as they may be considered clinically important. Informed consent: The nature and scope of the clinical study will be explained in an understand‐able way to the patients and an informed consent form, in Arabic language, including all the study procedures, advantages and possible risks and specifying who informed the patient, will be provided and the patient must sign on it before participation. The study protocol and patient informed consent will be reviewed and approved by the Ethics Committee of the Obstetrics and Gynecology Department, Ain Shams University. Funding: This study will be funded by the researcher himself and Ain Shams University Randomization and Allocation concealment: The participants will be randomly assigned into one of the two study groups using a computer random sequence generator. The randomization will be made using sequentially numbered, opaque sealed envelopes; each envelope contains the method of intervention according to the random sequence and will be opened just before the intervention. Study Procedures: All participants will undergo full assessment before starting either treatment options. This assessme will include: Detailed History: ‐ Personal history: including patient's full name, age, marital status, parity, occupation and residence will be recorded. ‐ Menstrual history: including age of menarche, D/C, amount of menstrual flow and associated dysmenorrhea. ‐ Contraceptive history: to exclude other causes for uterine bleeding. ‐ Past medical history of Diabetes Mellitus, hypertension, bronchial asthma, cardiac diseases, anemia, etc. ‐ Past surgical history of uterine surgeries. ‐ History of present illness with detailed analysis of each patient's complaint whether abnormal uterine bleeding, dysmenorrhea and pelvic pressure symptoms such as urinary urgency or constipation. Physical Examination: ‐ General examination including: Pulse, blood pressure, temperature, body mass index (BMI), auscultation of lungs and heart, and complex‐ion as pallor due to anemia caused by heavy bleeding. ‐ Abdominal examination: inspection for any scar, palpation of the abdomen for any tenderness and for pelviabdominal masses. ‐ Pelvic examination: complete bimanual examination for uterine size, mobility and palpable uterine fibroids. Investigations: ‐ Baseline hemoglobin, hematocrit, and blood grouping. ‐ Blood chemistry: AST, ALT, serum creatinine and RBS. ‐ Trans‐vaginal ultrasound for uterine volume and fibroid location, volume and maximum diameter. Uterine volume (expressed in cubic centimeters) will be calculated by measuring the maximum length, antero‐posterior and transverse diameters of the uterine corpus, using the US device software formula for calculation of the uterine volume. Myoma volumes will be measured by using the existing 2‐dimensional US methods. The FIGO classification system (figure 1) will be used for defining the myoma location. Study groups: Patients recruited in this study will be randomized into one of the following study groups: 1. Group A "Ulipristal Acetate (UA) ‐ Fibristal group" (n=35): Patients within this group will receive oral Ulipristal Acetate (Fibristal ©) 5 mg / day starting from the first day of menstrual bleeding, and for 3 months (period of the study). 2. Group B "Uterine artery embolization (UAE) group" (n=35): Patients within this group will undergo bilateral selective uterine artery embolization, during which polyvinyl alcohol (PVA) particles will be administered via a catheter followed by capping with a plug of gelatin sponge. The end point for embolization is to have a static column of contrast in the uterine artery, with only a stump filling when the internal iliac artery was injected. The gelatin sponge cap was thought to both complete the occlusion of the uterine artery and to prevent PVA particles from being drawn out of the uterine artery by the Venturi effect, which would result in non‐target embolization. Follow up: Each patient within both groups will be subjected to follow‐up trans‐vaginal ultrasound (US) 3 months after Ulipristal acetate (UA) therapy or after uterine artery embolization (UAE) session to detect the decline in uterine fibroid volumes in comparison to their baseline. To reduce inter‐observer variability associated with ultrasound imaging, measurements will be always taken by the same sonographer. Each patient within both groups will be evaluated clinically for the symptoms reported at least 1 month before starting the treatment (baseline) and 3 months after Ulipristal acetate (UA) therapy or after uterine artery embolization (UAE) session. Durability of the used treatment line will be tested by follow up after one year from initiating therapy. Fibroid‐related heavy menstrual bleeding (HMB) will be evaluated by the pictorial blood assessment chart score (figure 2). This instrument is a self‐administered pictorial chart that takes account of the number of sanitary pads and tampons used, presence of blood clots, and episodes of bleeding. The 1‐month pictorial blood assessment chart score was calculated from the addition of daily scores for 28 days. A score of higher than 100 during the first 8 days of menstruation will be efined as heavy menstrual bleeding (HMB). Subjective feelings of pelvic pressure, urinary urgency, and constipation will be recorded on a simplified questionnaire containing 2 categories defined as "absent "and "present." The visual analog scale (VAS) pain score (figure 3) will be used to determine the presence or absence of pelvic pain. Statistical Methods: Data will be analyzed using Intention to treat (ITT) analysis. According to Fisher et al (1990), the ITT analysis includes all randomized patients in the groups to which they were randomly assigned, regardless of their adherence with the entry criteria, regardless of the treatment they actually received, and regardless of subsequent withdrawal from treatment or deviation from the protocol. In other words, ITT analysis includes every subject who is randomized according to randomized treatment assignment. It ignores non‐compliance, protocol deviations, withdrawal, and anything that happens after randomization. ITT analysis is usually described as "once randomized, always analyzed". ITT analysis avoids overoptimistic estimates of the efficacy of one of the two interventions resulting from the removal of non‐compliers by accepting that noncompliance and protocol deviations are likely to occur in actual clinical practice. Efficacy of the two study interventions will be compared using Odds ratio (OR), Relative risk (RR), Number needed to treat (NNT) and Number needed to harm (NNH). Data will be analyzed using IBM© SPSS© Statistics version 23 (IBM© Corp., Armonk, NY). Normally distributed numerical data will be presented as mean and SD, and skewed data as median and interquartile range. Qualitative data will be presented as number and percentage. Normally distributed numerical data will be compared using the unpaired t test and skewed data using the Mann‐Whitney test. Categorical data will be compared using the Pearson chi‐squared test or Fisher's exact test, if appropriate. A two‐sided p‐value <0.05 will be considered statistically significant.

Nct (2021). "The Use of Dye-less Cystoscopy in Assessing Urinary Tract Integrity During Hysterectomy." ClinicalTrails.gov.
	Surgical injury to the urinary bladder and ureters is a recognized hazard with gynecologic procedures. Overall incidence is low; however, undetected injury to the bladder or ureter can be associated with avoidable morbidity. Approximately 75 to 85% of ureteral injuries are detected postoperatively. Various techniques have been investigated to prevent or detect genitourinary tract injuries during gynecologic surgery. Cystoscopy has been shown to increase the detection rate of urinary tract injury during gynecologic procedures compared to visual detection. Intra‐operative detection of urinary tract injury enables primary repair with high rates of success and avoidance of morbidity. Currently however, there is no standard recommendation for the routine use of cystoscopy in general gynecologic surgeries or in patients undergoing hysterectomy for gynecologic malignancies. Cost appears to be the main reason for the lack of a policy level endorsement of routine cystoscopy. One analysis concluded that ureteral injury rate was too low to justify routine cystoscopy, however other studies have reported higher urinary tract injury rates than previously published data, noted especially with the increasing use minimally invasive surgery. Removal of dye usage with cystoscopy can help mitigate the issue of cost associated with routine cystoscopy. Various dye agents are used to aid in the visualization of urine efflux. Multiple studies have evaluated the pros and cons of these dyes. The ability to perform cystoscopy without dye would decrease cost, if the accuracy of urinary tract injury identification is not compromised. The primary objective of this study is to assess the accuracy of dye‐less cystoscopy in the detection of urinary tract injury following hysterectomy. The investigators hypothesize that accurate cystoscopic evaluation for urinary tract injury at hysterectomy can be accomplished without the use of dye. This study is a randomized prospective evaluation in which patients undergoing hysterectomy for both benign and malignant conditions are randomized into one of four study arms: 1) dye/saline 2) dye/water 3) no‐dye/saline and 4) no‐dye/water. Following completion of hysterectomy patients undergo routine cystoscopy utilizing distending media and dye (or no dye) according to their assigned randomization. Two independent and blinded evaluations of the bilateral ureteral jet strengths is then performed using a continuous visual scale scoring system. Ureteral jet strength scores are then evaluated for inter‐observer correlation as well as comparison of jet strength and time until initial ureteral jetting is seen between the four randomized arms.

Nct (2021). "Use of Hypnosis in Hyperemesis Gravidarum." ClinicalTrails.gov.
	This prospective, randomised and single blind study, with the physician follow up the patients for nausea and vomiting not informed on the grouping of the patients, was carried out at a single center between January 2017 and January 2018. The study protocol was approved by the local Ethics Committee was conducted in accordance with the principles of the Declaration of Helsinki Written informed consent was obtained from the patients. Pregnant patients above the age of 18 years, admitted to the hospital with HG diagnosis were included in the study. HG was diagnosed on the basis of having at least one of the symptoms of ketonuria, weight loss in excess of 5% of the body weight and serious vomiting more than twice per day. Patients with known psychiatric disorders, organic diseases causing nausea and vomiting, HG diagnosis in previous pregnancy and experience in hypnosis, meditation and mindfullness, and those who were multiparous or could not be cooperative with the treatment team were excluded from the study. The patients were randomly assigned by means of picking closed envolopes to the Group H (GH) to receive hypnosis with conventional therapy and the Group C (GC) only to receive conventional therapy. Data on patient demographics, severity of nausea, numbers of vomiting per day, serum glucose, AST and ALT levels were recorded. Nausea and vomiting severity were evaluated 4 times per day using the Visual Analog Scale (VAS 0‐10; with 0=no nausea and10=extreme nausea). Conventional Ttreatment The treatment in HG is targeted to minimise the symptoms in order to reduce the adverse outcomes for the mother and the foetus. In our study, the conventional treatment was organized according to symptom severity, the clinical findings and the response given to the treatment. The basic protocol for the first 24 hours included intravenous hydration for 6 hours with NaCl (0.9 % x1000 cc) supplemented with KCL, the B1 and B6 vitamins. Oral feeding was restricted and the second step treatment choice comprising H1 receptor blocker dimenhydrinate (4 X 50 mg/day, po) was routinely used in all patients. When the VAS score was ≥4, the serotonin antagonist ondansetron (4mg, i.v.) was added to the treatment as the rescue medication. The daily nausea, numbers of vomiting were queried on a daily basis. The patients with vomiting incidence below 2 per day, tolerating oral nutrition and with urine cleared of ketonuria met the conditions of discharge. The duration of hospital stay and treatment procedures were followed and recorded. Hypnosis design Two sessions of hypnosis were carried out in addition to the conventional treatment on the first and second days of admission; and the paitents were instructed autohypnosis after the second session. This was repeated on the third day with the patients who could not satisfactorily acquire the technique and those who failed to succeed were excluded from the study. The GH included patients who carried out autohypnosis minimally 4 times per day.

Nct (2021). "Use of Ulipristal Acetate in Induction of Second Trimester Missed Abortion." ClinicalTrails.gov.
	The aim of this work is to assess the effectiveness and safety of Ulipristal Acetate in the management of 2nd trimester missed abortion along with misoprostol in pregnant women with previous caesarean section versus the use of misoprostol only with placebo as regards the time needed for abortion,Hypothesis: In pregnant women with 2nd trimester missed abortion with previous caesarean section , Ulipristal Acetate may decrease the time interval to achieve abortion when combined with Misoprostol in comparison to misoprostol alone.the included women divided to 2 groups Group A: will receive Ulipristal acetate 30mg, starting misoprostol 12 hours later 100µg every 6 hours buccal according to FIGO guidelines 2017.Group B: will receive placebo then 12 hours later start misoprostol 100µg every 6 hours buccal according to FIGO guidelines 2017. then we assess Induction‐to‐abortion interval time.

Nct (2021). "Vaginal Cuff Closure by Modification of the Bakay Technique in Total Laparoscopic Hysterectomy." ClinicalTrails.gov.
	The basis for minimizing the rate of severe haemorrhage and ureteral injuries, the most serious events related to these steps, is meticulous dissection providing a clear operative field and the skill and experience of the surgeon. In total laparoscopic hysterectomy (TLH), the altered anatomy after the removal of the uterus may cause the retraction of vagina and shifting of neighbouring structures such as bladder and/or bowel to this pouch, thereby, leading to obstruction of the operative field for vaginal cuff closure. Bakay published his novel colpotomy and cuff closure technique for TLH. It was the first to describe placing a single continuous running purse‐string suture facilitating the cuff closure before colpotomy. The main advantage of the technique involved retrieving the safe suture margins required for vaginal cuff closure before the pelvic anatomy was altered by the removal of the uterus. In addition to this advantage, we modified the technique to achieve a better cuff healing and standardized apical support and the modified Bakay technique (MT) proposes: i) placing a single continuous running purse‐string suture for vaginal cuff closure before the pelvic anatomy is altered by the colpotomy and removal of the uterus; ii) suspension/plication of USLs (as a well‐defined, efficient, concomitant apical support procedure to prevent future vaginal vault prolapse) routinely in each case before colpotomy while the margins of these ligaments and adjacent structures such as ureters are still prominent and pelvic anatomy is not altered; and iii) using cold‐knife colpotomy instead of electrosurgical colpotomy to support the primary healing of the vaginal cuff. In the present study, we aimed to compare the surgical and clinical outcomes of the MT to standard technique (ST) in patients undergoing TLH.

Nct (2021). "Vaginal Hygiene Wash as Adjunct Treatment in Bacterial Vaginosis." ClinicalTrails.gov.
	This is a randomized controlled trial comparing the trial hygiene wash against placebo wash as adjunct treatment with oral metronidazole in women with bacterial vaginosis, with microbial analysis of vaginal flora compared to healthy control women

Nct (2021). "Venous Thromboembolism Prophylaxis After Gynecological Pelvic Cancer Surgery With Rivaroxaban vs Enoxaparin." ClinicalTrails.gov.
	Cancer‐associated thrombosis is the second leading cause of mortality in cancer patients, mainly due to the most common complication, venous thromboembolism (VTE). New oral antithrombotic strategies for VTE prevention after gynecological cancer surgery might be non‐inferior to parenteral low‐molecular‐weight heparin (LMWH) in efficacy and safety with increased adherence, comfort, and reduced costs. This is a multicenter, open‐label, prospective, randomized, active‐controlled study, and non‐inferiority trial. Four hundred and forty patients submitted to major gynecological cancer surgery will be randomized in a 1:1 ratio to receive either oral rivaroxaban 10 mg once daily or subcutaneous enoxaparin 40mg once daily for 30 days post‐operative. The primary efficacy outcome is a combination of symptomatic VTE and VTE‐related death or VTE detected by mandatory Doppler ultrasound on day 30±4 post‐operative. The primary safety outcome is the incidence of major and clinically relevant non‐major bleeding according to the International Society on Thrombosis and Hemostasis criteria.

Nct (2021). "Virtual Reality During Ultrasound Examination of Women With Endometriosis." ClinicalTrails.gov.
	A prospective, open‐label, randomized control trial in a tertiary university‐affiliated medical center between April to August 2020. Overall, 100 women will be randomly allocated to undergo ultrasound exam either with the use of VR (study group) or with standard treatment (control group). The primary outcome measures includ self‐reported pain, anxiety scores, and vital parameters as pulse rate (PR) and respiratory rate (RR). Pain and anxiety outcomes were measured as numeric rating scores.

Nct (2021). "vNOTES Salpingo-oophorectomy or Bilateral Salpingectomy Compared With Laparoscopic." ClinicalTrails.gov.
	Objective: To compare the vNOTES approach versus conventional laparoscopic approach used in elective Salpingo‐oophorectomy surgery for benign disease or bilateral salpingectomy for sterilization. Study design: Prospective cohort, randomized controlled trial. Study population: women aged over 18 who are planned to elective Salpingo‐oophorectomy for benign disease or bilateral salpingectomy for sterilization. Primary outcome ‐ Removal of the ovaries and/or fallopian tubes according to the allocated technique, without conversion. Secondary outcome ‐ Duration of the surgical procedure, Duration of hospital admission (after surgery), The need for analgesics, and pain Numerical Rating Scale score , Post operation infection (up to 4 weeks from surgery), Need for medical examination/treatment or appearance of surgical complication up to 4 weeks form surgery (using Clavin Dindo Class), Bleeding assessment during surgery, Dyspareunia assessment ‐ up to 3 months from surgery, Patient satisfaction from the surgical procedure will be measured with Patient Global Impression of Improvement (PGI‐I).

Nct (2022). "Abdominal Muscles Strengthening And Pelvic Floor Muscle Strengthening Exercises In Females With Urinary Incontinence." ClinicalTrails.gov.
	Urinary incontinence is common females., it badly affects their performance and result in psychosocial problems in addition to the barriers that already have been resulted from incontinence. This study combines simple regime of hip adductor a strengthening with pelvic floor muscles. The theme is to test if pelvic floor muscle training can be augmented by incorporating adductor muscle strengthening. If this comes out to be effective, this can be great contribution to gym doing females to improve their urinary incontinence related impairments. Woman would be encouraged to continue regular exercise. This will be randomized clinical trial. There are two groups for the compression of adductors strengthening and pelvic floor muscle strengthening. Group A: with pelvic floor muscle strengthening is strengthening. Group B: abdominal muscles strengthening exercises. The collected data will be entered in SPSS 20.0, Descriptive and Inferential statists will be applied. Results and conclusion will be drawn.

Nct (2022). "Acupuncture With/Without Self-acupressure for Post-oophorectomy Hot Flashes in BRCA Carriers." ClinicalTrails.gov.
	Risk‐reducing surgery with salpingo‐oophorectomy (RRSO) is the standard recommended treatment for all female carriers of BRCA genes 1 and 2. The post‐surgical menopause induced is invariably accompanied by hot flashes and other symptoms, which can severely impair quality of life and function. Hormone‐replacement therapy (HRT) is the standard conventional treatment for these symptoms, though these drugs do not always provide adequate relief and many patients either cannot receive them due to a diagnosis of breast cancer or hypercoagulable state; or are unwilling to take them due to their concern about the associated increased risk for developing hormone‐induced breast cancer. Acupuncture and acupressure have been researched extensively and shown to be both safe and effective in reducing hot flashes in post‐menopausal patients and in those with breast cancer receiving anti‐hormonal drugs. The present study will examine the effectiveness of acupuncture, with/without self‐acupressure, on 200 post‐ RRSO patients who suffer from at least 5 hot flashes per day, including those treated with HRT. All participants will receive 8 weekly treatments with acupuncture, and then randomly assigned to receive (or not) self‐administered acupressure, to be performed daily at home. The response to the study interventions will be assessed using daily Hot Flash Scores, the Menopause Specific Quality of Life (MenQoL) and Measure Yourself Concerns and Wellbeing (MYCAW) questionnaires (at baseline; at the end of the 8‐week intervention; and at 16 weeks). The safety of the study treatments will be assessed throughout.

Nct (2022). "ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in HLA-A2+ Subjects With MAGE-A4 Positive Ovarian Cancer (SURPASS-3)." ClinicalTrails.gov.
	This is a phase 2, open‐label, randomized, non‐comparative clinical trial to evaluate the clinical outcome of ADP A2M4CD8 as monotherapy and in combination treatment with nivolumab in human leukocyte antigen (HLA) A2+ subjects with recurrent ovarian cancer positive for MAGE‐A4.

Nct (2022). "Art Therapy in Obstetric Patients." ClinicalTrails.gov.
	The purpose of this research study is to assess whether alternative mental health interventions positively impacts maternal‐infant bonding and postpartum depression rates in women. Postpartum depression continues to be a prevalent concern for mothers and families in the United States, with current estimates demonstrating 10‐20% of women being diagnosed within one year of birth. The risks of developing postpartum depression are not well known, with maternal anxiety and stress during pregnancy being one of the proposed predisposing factors. Women with high‐risk pregnancies are particularly susceptible to higher levels of stress and depression, during their pregnancy thus leaving them at great risk for postnatal depression. Given this association, finding ways to alleviate stressors is important. Music therapy is a known intervention linked with improved outcomes in women undergoing procedural interventions, including labor and delivery. Art therapy is also associated with improved outcomes, though outside of obstetrics. In elderly women with depression and those with breast cancer diagnoses, visual art therapy has been shown to be superior to other non‐medicinal interventions in improving mood. Current data is both qualitative as well as quantitative, demonstrating positive impacts on patients. While evidence exists to support the utilization of these alternative forms of therapy, they have not been adequately applied to pregnant and postpartum women outside of music therapy. With the understanding that other art forms are tied with improvement in anxiety, depression, and quality of life, the implementation in this special patient population is paramount. Investigating how a relatively benign intervention can possibly promote improvement in maternal mental health, thus allowing for better mother‐baby bonding in the first year of life, is key in finding ways to support the growth and development of healthy families.

Nct (2022). "Auriculo-Nerve Stimulation on Post-Operative Opioid Requirement." ClinicalTrails.gov.
	It is established that the perioperative prescription of opioids, including doses prescribed after discharge from the hospitals, is an important contributor to the current opioid epidemic. Although many factors have been implicated including history of addiction, mood disorders and the type of surgery, the quantity and duration of opioid treatment play an important role in a patient's development of opioid use disorder (OUD). Despite recommendations by the majority of surgery and anesthesiology professionals to limit the perioperative use of opioids, and to favor the use of non‐opioid analgesics, OUD remains a serious concern. Consequently, developing alternative techniques to minimize the perioperative use of opioids is critical in the fight against the current opioid epidemic. Auriculotherapy, a form of acupuncture is an ancient technique used to treat many conditions, including pain. Its mechanism of action is believed to be primarily via the stimulation of the branches of the vagal, trigeminal, glossopharyngeal, hypogastric, facial and superficial cervical plexus nerves innervating which secondarily modulate the pain pathway and the limbic system at the level of the brainstem, spin and central nervous system. However, the use of auriculotherapy has been limited in part by the requirement for long and specific training and the lack of well‐designed clinical trials demonstrating its effectiveness. This study design is based on the high frequency of OUD following surgery for cancer and the positive results from our exploratory Institutional Review Board (IRB)‐ approved, randomized and placebo‐controlled pilot study that assessed the effects of the NSS‐2 BRIDGE® device on perioperative pain and opioid requirement in different surgical oncology models. This was a study that included subjects undergoing both open and laparoscopic procedures of different types of surgeries for abdominal cancer.

Nct (2022). "BACK MASSAGE APPLIED CLIMACTERIC WOMEN MENOPAUSAL COMPLAINTS, SLEEP QUALITY AND MARITAL ADJUSTMENT." ClinicalTrails.gov.
	Climacterium is a life period in which women move from the reproductive age to the period when their reproductive ability is lost due to the decrease in ovarian functions. The most common climacteric disorder is vasomotor changes. The most common problem seen in menopausal period after vasomotor complaints is insomnia. Sleep disorders seen in climacteric period negatively affect the quality of life and psychosocial health of woman. In their study, Jean‐Louis et al., expressed that women in menopausal period spent approximately 10% of their daily sleep time by sleeping outside the bed during the day. 61% of menopausal women woke up at least once a week and several times from the night's sleep. In their study, Anttalainen et al., determined that women in postmenopausal period had more sleep problems compared to women in premenopausal period. In addition to physical changes due to hormonal changes in climacterium, mental problems such as nervousness, anxiety and depression developing in women may negatively affect the relationships in family environment especially the communication with the spouse. Besides, it is thought that an incompatible marriage can increase menopausal complaints. In the studies investigating the relationship between menopausal complaints and marital adjustment, women with compatible marital life were found to experience less menopausal complaints. Due to the negative effects of physician‐controlled hormone replacement treatment administered to reduce menopausal symptoms, demand for non‐pharmacological interventions has increased and women have started to accept that therapeutic massage is safe and contributes to health. It is stated that women experience insomnia, a symptom of menopause, and tend to choose especially body therapies from alternative therapies in the first place. Massage is widely accepted as a treatment tool. Although the menopausal period is physiological, it is a period that must be addressed specifically by healthcare professionals since it is accompanied by pathological events causing distress in life and impairing the quality of life. The purpose of this study is to determine the effect of back massage applied by partners on menopausal complaints, sleep quality, and marital adjustment of women in climacteric period.

Nct (2022). "Bacterial Composition and Recurrent Cystitis in Postmenopausal Women After Treatment With Lactobacilli." ClinicalTrails.gov.
	The goal of this clinical trial is to learn about the effect on the bacterial composition in the microbiome (the body's own bacteria) of urine, vagina and faeces after treatment with lactobacilli (lactobacilli's are a part of the microbiome), and its influence on repeated cystitis in postmenopausal women. The main questions it aims to answer are: ‐ Does treatment with lactobacilli change the composition of the urine microbiome in postmenopausal women? ‐ Does treatment with lactobacilli prevent repeated cystitis in postmenopausal women? Participants will be followed for 6 months. They will for 3 months receive a look‐alike substance that contains no active drug and for the other 3 months tablets with lactobacilli. A computer program will decide what treatment the participant will begin with, and after 3 months she will be receiving the tablets, she did not get first. This way all participants receive both type of tablets and can be their own control. What type of tablet the participants is taking is unknown to both clinical staff and participants. The participants will come to the hospital for start‐up, and every 1,5 moths for the next 6 months. They deliver ‐ faeces sample ‐ urine tests ‐ vaginal swab each time they are seen. When entering the study, they also complete health care questions on medication, earlier surgery, alcohol, tobacco, childbirths, weight, height etc. They make a drinking and voiding diary 3 times over the 6 months. When the study is over, alle the samples of faeces, urine and the vaginal swab will undergo analyzation for the bacterial composition in the microbiome, and differences in the microbiome when taking lactobacilli or not will be examined. The urine sample is controlled for bacteria known to give cystitis, and the influence on repeated cystitis will also be examined.

Nct (2022). "Better Lifestyle Counseling for African American Women During Pregnancy." ClinicalTrails.gov.
	This is a randomized controlled parallel‐group trial with two arms. Potential subjects will be identified from the OB Clinics at UI health systems, the University of Illinois at Chicago. After baseline assessments, the subjects will be randomized to the attention control arm (Birth‐Prep) or BETTER intervention.

Nct (2022). "Biofeedback Versus Vaginal Palpation to Teach a Voluntary Pelvic Floor Muscle Contraction." ClinicalTrails.gov.
	Randomised, parallel (two arm), trial comparing biofeedback (experimental arm) versus vaginal palpation (active control, i.e. usual practice) to achieve a correct voluntary pelvic floor muscle contraction in women who cannot perform a correct contraction (i.e. grade 0, 1 or 2 on the Modified Oxford Scale). The trial hypothesis is that there is no difference between the two trial arms in the proportion of women achieving a correct voluntary contract (grade 3 or better). The training protocol will be the same for both groups and will vary according to PFM function assessed at 0, 3, 6 and 9‐week timepoint. The resting time after each contraction will be the double of the contraction duration, therefore if it is performed a 3‐second contraction, it will be a 6‐second rest. The first session will aim to improve some skills as understanding, searching, and finding PFM, the educational component of this session was structured considering Health Belief Model and will be conducted with the following information: 1) General information (female genital anatomy, female intern organs, pelvic floor muscle anatomy, pelvic floor muscle function), 2) specific information about urinary incontinence (definition of urinary incontinence, predictors of risk for urinary incontinence, impact on quality of life), 3) the relation between PFM and urinary incontinence, 4) pelvic floor muscle training as first line treatment for urinary incontinence, 5) how to include PFM proprioception protocol into daily life. It will be used as educational materials images and draws of the region and an educational booklet will be delivered to them. It will be shown to then a video of a PFM contraction emphasizing how the correct PFM contraction is supposed to be. The other sessions will focus will vary according to PFM function accessed at each timepoint: ‐ Participants classified with MOS 0 or 1: PFM protocol will aim on learning a PFM contraction and improve PFM perception ‐ Participants classified with MOS = 2: PFM protocol will aim on teaching how to control PFM contraction ‐ Participants classified with MOS ≥ 3: PFM protocol will aim on improving PFM strength The resting time after each set will be 3 minutes and the protocol will evolve as following: ‐ WEEK 1: In clinics: 30 minutes: educational component as previous discussed. 30 minutes: The studied protocol will be explained as well as the need to fulfill a diary with their home training routine that should be delivered to the evaluator at the 12‐week assessment. At each session, the physiotherapist will oversee the diary, take notes about the frequency of training, and orientate if necessary. To promote a first contact with their PFM, it will be performed 1 set of PFM contraction associated with vaginal palpation or biofeedback of 6 fast contraction according to the randomized group. The resting time after each contraction will be five seconds. Possible doubts will be clarified. At home: All participants will be oriented to perform 3 sets of 6 fast contraction daily during the following week in the supine position. The resting time after each contraction will be five seconds and after each set will be 2 minutes. ‐ WEEK 2‐3: In clinics: Training diary will be overseen, and possible doubts will be clarified. Training protocol will be different according to PFM function assessed on week 0. MOS 0: 3 sets of 6 fast contraction. The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 6 fast contraction and 3 sets of 6 contractions sustained for 3 seconds. The resting time after each contraction will be five seconds and 2 minutes after each set. At home: Training protocol will be different according to PFM function assessed on week 0. MOS 0: 3 sets of 6 fast contraction in supine position. The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 6 fast contraction and 3 sets of 6 contractions sustained for 3 seconds in supine. The resting time after each contractio ill be five seconds and 2 minutes after each set. ‐ WEEK 4‐6: In clinics: Training diary will be overseen, and possible doubts will be clarified. Training protocol will be different according to PFM function assessed on week 3. MOS 0: 3 sets of 10 fast contraction. The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 10 fast contraction and 3 sets of 6 contractions sustained for 4 seconds. The resting time after each contraction will be six seconds and 2 minutes after each set. MOS ≥ 2: 3 sets of 10 fast contraction and 3 sets of 10 contractions sustained for 6 seconds. The resting time after each contraction will be ten seconds and 3 minutes after each set. At home: Training protocol will be different according to PFM function assessed on week 3. MOS 0: 3 sets of 10 fast contraction, each set on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 10 fast contraction and 3 sets of 6 contractions sustained for 4 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be six seconds and 2 minutes after each set. MOS ≥ 2: 3 sets of 10 fast contraction and 3 sets of 10 contractions sustained for 6 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be ten seconds and 3 minutes after each set. ‐ WEEK 7‐9: In clinics: Training diary will be overseen, and possible doubts will be clarified. Training protocol will be different according to PFM function assessed on week 6. MOS 0: 3 sets of 10 fast contraction and 3 sets of 5 contraction sustained for 3 seconds. The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 10 fast contraction and 3 sets of 6 contractions sustained for 4 seconds. The resting time after each contraction will be six seconds and 2 minutes after each set. MOS ≥ 2: 3 sets of 10 fast contraction and 3 sets of 10 contractions sustained for 6 seconds. The resting time after each contraction will be ten seconds and 3 minutes after each set. At home: Training protocol will be different according to PFM function assessed on week 6. MOS 0: 3 sets of 10 fast contraction and 3 sets of 5 contraction sustained for 3 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 10 fast contraction and 3 sets of 6 contractions sustained for 4 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be six seconds and 2 minutes after each set. MOS ≥ 2: 3 sets of 10 fast contraction and 3 sets of 10 contractions sustained for 6 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be ten seconds and 3 minutes after each set. ‐ WEEK 10‐12: In clinics: Training diary will be overseen, and possible doubts will be clarified. Training protocol will be different according to PFM function assessed on week 9. MOS 0: 3 sets of 10 fast contraction and 3 sets of 5 contraction sustained for 3 seconds. The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 10 fast contraction and 3 sets of 6 contractions sustained for 4 seconds. The resting time after each contraction will be six seconds and 2 minutes after each set. MOS ≥ 2: 3 sets of 10 fast contraction and 3 sets of 10 contractions sustained for 6 seconds. The resting time after each contraction will be ten seconds and 3 minutes after each set. At home: Training protocol will be different according to PFM function assesse o week 6. MOS 0: 3 sets of 10 fast contraction and 3 sets of 5 contraction sustained for 3 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be five seconds and after each set will be 2 minutes. MOS 1: 3 sets of 10 fast contraction and 3 sets of 6 contractions sustained for 4 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be six seconds and 2 minutes after each set. MOS ≥ 2: 3 sets of 10 fast contraction and 3 sets of 10 contractions sustained for 6 seconds. Each set is supposed to be performed on a different position (i.e. supine, sitting and standing). The resting time after each contraction will be ten seconds and 3 minutes after each set. The two groups will receive a booklet and guidance to perform the training protocol at home on alternate days and a diary to register their adherence to the program. The guided protocol will be the same used during the supervised training on that specific week. Women will be oriented to choose the position to practice unsupervised sessions (i.e. supine,lateral, sitting and/or standing).

Nct (2022). "Bladder Complaints in Parkinson's Disease Effectiveness of Pelvic Floor Muscle Exercises and Electrical Stimulation." ClinicalTrails.gov.
	Parkinson's disease (PD) is the second most common degenerative neurological disease in the elderly. PD is predominantly a movement disorder. In addition, PD is associated with non‐motor and autonomic symptoms. Over 75% of PD patients, experience lower urinary tract symptoms (LUTS), one of the most common autonomic symptoms. LUTS consists of urgency, frequency and nocturia with or without urinary incontinence (UI). More than 60% of PD patients experience nocturia. LUTS have a negative impact on Quality of Life(QoL), increases the risk of falls are a barrier to exercise and may lead to early admission into care. Therefore, this potentially increases healthcare related costs. First treatment options for LUTS in the general population are conservative therapy and medication. Conservative therapy consists of e.g., behavioral advice, bladder training, pelvic floor muscle exercises provided by a pelvic physical therapist(PPT) and, electrical stimulation(ES). Knowledge of the effectiveness of conservative treatment options for LUTS in PD is limited. Although ES is used effectively in patients with LUTS, it has not yet been studied in PD patients. ES has hardly any side effects, but there is uncertainty about optimal ES parameters. Objective: to study the effectiveness of pelvic physical therapy and ES in patients with PD suffering from LUTS. Study design: Randomized Controlled Trial (RCT). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Questionnaires are online, allowing participants to complete the questionnaires at home at a convenient time. Participants may have direct benefits of participating in this study. Participants included in the study will have two additional visits to a research PPT that will last one hour each, at baseline and after treatment. During this visit, a digital pelvic floor muscle (PFM) assessment and an EMG measurement of the PFM will be performed. EMG measurement will be done with a small anal‐ or vaginal probe. No risks are associated with the use of this probe. Participants will be referred to local PPT's close to the subjects home address for the treatment sessions. Intervention: eight treatment sessions of 30 minutes pelvic physical therapy over a 10‐week period. The intervention consists of bladder‐ and behavioral advice, pelvic floor muscle exercises (PFME), urge suppression techniques, biofeedback and ES with an intra anal or intra vaginal probe. The group is divided into three groups. Group 1: ES with small pulse duration, group 2: ES with broad pulse duration, group 3: (control group) receiving sham ES. No adverse events are expected since pelvic physical therapy and ES in LUTS is usual care in the general population in the Netherlands. Expected burden for the participants is very low.

Nct (2022). "Body Surface Area-based vs Concentration-based Dosing of Cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Women With Advanced Ovarian Cancer." ClinicalTrails.gov.
	Cytoreductive surgery (CRS) with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) is used in current clinical practice in selected patients with advanced ovarian cancer. Clinical evidence for the benefit of HIPEC in ovarian cancer comes from the pivotal phase 3 OVHIPEC trial. Worldwide, two established strategies exist for dosing of HIPEC protocols, which follow either a body surface area (BSA)‐based or a concentration‐based approach. Since both strategies result in different exposure to intra‐peritoneal chemotherapy, we aim to compare the pharmacokinetics and safety of both strategies.

Nct (2022). "Cannabidiol for the Treatment of Pelvic Pain in Endometriosis (DREAMLAND)." ClinicalTrails.gov.
	The Dreamland study is a two‐arm, parallel‐group, individually randomized (1:1 allocation ratio), controlled by disease stage, participant and investigator blinded, single‐site superiority trial of oral cannabis extract (CBD). CBD will be given orally starting at 10 mg daily and up‐titrated to a maximum dose of 150 mg daily. Dose up‐titration will be based on clinical response or side effects, whichever comes first. After 63 days of treatment, gradual withdrawal will be performed during one week. Then, at 70 days, there will be an open‐label extension wherein all participants from control group will be offered a course of CBD according to the same previous protocol. This research intends to : 1. Assess whether the daily use of CBD, for nine weeks, will reduce the pain level of these women. 2. Assess whether the daily use of CBD, for nine weeks, will modify pain threshold. 3. Assess whether the daily use of CBD, for nine weeks, will interfere in psychological symptoms. 4. Assess the possible adverse effects of using CBD

Nct (2022). "Cervical Occlusion Double-level Stitch Application." ClinicalTrails.gov.
	This is an open‐label, multicentre, prospective, randomised controlled trial (RCT). Women will be randomized to the single‐level cerclage arm or the double‐level cerclage. Each patient will have a vaginal swab for aerobic and anaerobic bacteria and fungi culture, as well as for mycoplasmas, chlamydia and ureaplasma performed. Each patient will be treated with progesterone (vaginally 2 x 100 mg per day) and empirical antibiotic therapy (ceftriaxone 2.0 g iv + clarithromycin 2 x 500 mg po + metronidazole 3 x 500 mg iv for 7 days). If specific pathogens will be detected, the antibiotic therapy will be modified according to the antibiogram. If the diagnosis of cervical insufficiency will be made >23 weeks of gestation a single course of corticosteroid therapy will be administered (betamethasone 2 x 12 mg im) if the rsik of delivery within 7 days will be assessed as high. Indomethacin will also be administered for 48 hours (starting the day of cerclage administration, indomethacin 2 x 75 mg po for 48 hours). In the single‐level cerclage arm McDonald suture will be administered. In the double‐level cerclage arm two separate sutures analogous to McDonald technique will be placed, one approximately 1 cm higher above the other. Patients will be followed up until miscarriage or delivery and will receive standard perinatal care. Gestational age at delivery, the occurrence of cerclage complications and neonatal outcomes will be analyzed.

Nct (2022). "Chemotherapy vs Chemoradiotherapy for Post-operative Endometrial Cancer Patients With P53-mutation." ClinicalTrails.gov.
	According to tumor molecular characteristic, endometrial cancer can be divided into four types with different biological behaviors and prognosis: POLE hypermutation （POLEmut）, Mismatch repair system defect (MMRd), Non special molecular feature (NSMP) and P53 mutation (p53mut) For the postoperative therapy, preliminary data showed that p53mut endometrial cancer was more sensitive to chemotherapy. Therefore, we propose a hypothesis: for p53mut endometrial carcinoma, compared with chemoradiotherapy, postoperative chemotherapy alone had similar effects on the prognosis and similar treatment‐related adverse reactions, but could avoid radiotherapy‐related adverse effects and reduce medical expenses. And more high‐quality evidence is needed to prove the hypothesis. This study were approved by the Fudan University Shanghai Cancer Center and all other institutes. Before initiation of study procedures, written informed consent will be obtained from each patient regarding risks of treatments and agreement of using their clinical data for research purpose. Patients will be stratified into 4 layers by surgical pathological staging (FIGO 2009), preoperative and postoperative imaging evaluation, surgical conditions and postoperative pathology : stage IA,stage IB‐II, stage III‐IVA ( no residual lesion after operation), any stage with maximum diameter of residual lesion <2cm (except stage IVB). After stratification, Eligible patients in each stratification of each center will be randomly assigned (1:1) to receive: Arm1:Paclitaxel plus carboplatin (TC) regimen, intravenous chemotherapy. Once every three weeks, a total of 6 course. Arm2: Stage IA: TC regimen for 4 course+VBT. Stage IB‐IVA (no residual lesion after operation) and any stage with maximum diameter of residual lesion <2cm (except stage IVB): TC regimen for 2 course +EBRT (external irradiation radiotherapy) plus cisplatin concurrent chemotherapy +TC regimen for 2 course (same as above) ±VBT. The specific implementation plan should be performed after NCCN(2022 V1.) and ESGO guidelines, and adjuvant therapy is preferably started within 4‐6 weeks after surgery and no later than 8 weeks after surgery. The main research indicators of this study: PFS at 2 years after operation. Secondary research indicators: 3 years postoperative PFS and 5 years postoperative PFS and OS; adverse effects; quality of life; medical expenses; site of recurrence. And expression of molecular markers: Explore the correlation between the expression of molecular markers involved in IHC proteomics and molecular typing gene mutation detection of tumor tissue and therapeutic efficacy. This study is an open label randomized controlled trial with non‐inferiority design.Statistical analyses On the basis of data from previous studies (PORTEC‐3, GOG‐258, GOG‐249 and Molecular Classification Of G3 EEC, etc.), the 2‐year PFS of radiochemotherapy group is expected to be 75%, if that in chemotherapy‐alone group was 65% and above,this group should not to be considered to be inferior, and the unilateral α level is 0.05, 80% of the detection efficiency. After patient stratification in each center, two groups were allocated by 1:1, with 15% total withdrawal groups and lost follow up rates, with an expected recruitment for 5 years and 5 years of follow‐up.

Nct (2022). "Circadian as A Prognostic Factor For Radiation Response in Cervical Cancer." ClinicalTrails.gov.
	The study was a Randomized Clinical Trial (RCT) or clinical trial comparing the results of radiation treatment of 2 treatment groups, i.e. subject groups irradiated in the morning and in the afternoon, to check melatonin levels in cervical cancer patients. Since it is known that the function of melatonin is as an antiproliferation substance or hormone, induces apoptosis, inhibits invasion and metastasis.

Nct (2022). "A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia and Pain." ClinicalTrails.gov.
	Multi‐center, randomized, double‐blind, parallel‐group study to confirm superiority of KLH‐2109 to placebo in uterine fibroids patient with menorrhagia and pain

Nct (2022). "CO2 Laser vs Lidocaine for Vestibulodynia in Premenopausal Women." ClinicalTrails.gov.
	The purpose of this study is to see if vaginal laser therapy with MonaLisa Touch® will be more effective in treating vestibulodynia than current treatment with a topical lidocaine ointment. Vestibulodynia is a common bothersome condition and is more likely to occur in women on hormonal contraceptive treatment. To date, there are no effective treatments that address the underlying causes of the disease. MonaLisa Touch® is a laser procedure that delivers CO2 laser energy to the vaginal wall tissue. This energy causes the patient's own body to regenerate collagen and blood vessels, changing the tissue to make it healthier. The MonaLisa Touch® technology may help vestibulodynia by potentially fixing the underlying cause. This may be more effective than using the topical lidocaine which makes the tissue numb.

Nct (2022). "Comparative Analysis of Spinal Anesthesia Versus General Anesthesia for vNOTES." ClinicalTrails.gov.
	Anesthesia is a controlled, temporary loss of sensation or awareness used to perform surgical procedures. Spinal anesthesia is commonly used in obstetrics and gynecology for vaginal procedures as well as cesarean sections. The use of spinal anesthesia for laparoscopic surgery is an adequate and safe alternative to general anesthesia which remains the gold standard. Vaginal Natural Orifice Endoscopic Surgery (vNOTES) is a minimally invasive laparoscopic approach used for tubal sterilization that is currently performed under general anesthesia. This study is proposing that spinal anesthesia is an adequate and safe alternative to general anesthesia for vNOTES tubal sterilization. If participants join the study, all other routine care will continue but the researchers will randomly assign participants, like flipping a coin, to one of two groups. Both types of anesthesia are commonly used but the researchers are doing this study because it is not known if spinal anesthesia is a better alternative than general anesthesia which is typically used. The goal is to find out what might be best for future patients. If it turns out the two types of anesthesia are about the same, then surgeons would know that choosing the type with fewer side effects still gives satisfactory results and allows for this surgery to be performed safely. The risks involved in participating in this study are the same as all other anesthetic and surgical procedures which have significant physical risks. If participants choose to enroll, there will be a 50/50 chance of being assigned to either the standard of care group which will receive general anesthesia or the experimental group which will receive spinal anesthesia. Benefits cannot be guaranteed but, It is possible participants could be assigned to a type of anesthesia that has fewer side effects.

Nct (2022). "COMPARATIVE STUDY BETWEEN THE EFFECT Of AEROBIC EXERCISES ON LAND AND AEROBIC EXERCISES IN WATER ON PMS SYNDROME." ClinicalTrails.gov.
	Fourty adolescent girls were divided randomly into two equal groups, Group (A) will consist of (20) adolescent girls age ranged from 14‐17 suffering from PMS without any pathological cause they will receive an aerobic exercise on land in form of walking on the treadmill for 20 min 3 times per week for 3 months. Group (B) will consist of (20) adolescent girls age ranged from 14‐17 suffering from PMS without any pathological cause they will receive an aerobic exercises in water in form of walking on the treadmill for 20 min 3 times per week for 3 months the assessment of the PMS symptoms will be done by Premenstrual distress questionnaire

Nct (2022). "Comparative Study Between Vaginal Progesterone Alone or Combined With Aspirin in Prevention of Recurrent Preterm Birth." ClinicalTrails.gov.
	The included women will be randomly allocated to prophylactically receive either vaginal progesterone at a dose of 200 mg (prontogest 200mg every 12 hr) combined with oral aspirin at a dose of 100mg once daily both at the same time (group1), or vaginal progesterone (prontogest 200mg every 12 hr) and oral placebo (manufactured in a standard way to have the same size and shape of asprin tablet) also at the same time (group 2).

Nct (2022). "Comparing of Cefazolin Plus Azithromycin Versus Cefazolin in Prevention of Febrile Morbidity After Emergency Cesarean Delivery." ClinicalTrails.gov.
	This study was designed to evaluate the effect of azithromycin on the incidence of febrile morbidity after the emergency cesarean section. The standard antimicrobial prophylaxis which is recommended by the ACOG is the 1st generation cephalosporin intravenously only but some of the bacteria that can cause the febrile morbidity after cesarean section wouldn't be killed by the 1st generation cephalosporin. The antibiotic that can cover them is macrolide group antibiotic such as azithromycin. Therefore this study will compare the regimen of standard antimicrobial prophylaxis and the regimen of standard antimicrobial prophylaxis with azithromycin intravenously in preventing the febrile morbidity after emergency cesarean section. Control group will receive the 1st generation cephalosporin intravenously and the intervention group will receive the 1st generation cephalosporin with azithromycin 500mg intravenously. Primary outcome is febrile morbidity which assessed at postoperative day 3. The definition of the febrile morbidity in this study is including surgical site infection, endometritis, urinary tract infection and fever alone. Secondary outcomes are febrile morbidity at postoperative day 7 and day30, neonatal outcome and adverse effect from azithromycin use.

Nct (2022). "Comparing Two Prophylactic Antibiotic Protocols in Women With Term Prolonged Pre-labor Rupture of Membrane and Preterm Labor." ClinicalTrails.gov.
	Maternal peripartum fever is a common complication of pregnancy and postpartum period associated with potentially serious obstetrical outcomes and infectious morbidity. Peripartum infections includes intrapartum intraamniotic infection (IAI) and postpartum endometritis. Both are caused by polymicrobial bacterial infection. Increased latency period from rupture of membranes (ROM) until delivery is a common risk factor. Another risk factor is pre‐term delivery. This randomized prospective trial aimed to compare 2 prophylactic antibiotic regiment (ampicillin alone versus ampicillin plus gentamycin) in term prolonged pre‐labor rupture of membrane and in preterm deliveries and examine related obstetrical outcome and infectious morbidity. Primary outcome‐peripartum infections‐ chorioamnionitis, endometritis and surgical site infection secondary outcome‐ obstetrical outcome‐ mode of delivery, Apgar score, cord blood pH, peripartum fever, maternal length of admission, postpartum maternal antibiotic treatment, Surface swab cultures were obtained from the placenta, amnion and umbilical cord (birth cultures) and uterine swab cultures, maternal blood culture, placental histologic evaluation neonatal outcomes‐NICU admission, length of admission, neonatal morbidity‐ventilation support, early neonatal sepsis

Nct (2022). "Comparison Between Letrozole and Mifepristone in Medical Termination of First Trimester Miscarriages." ClinicalTrails.gov.
	Prospective interventional study where participants with non‐viable pregnancy at 1st trimester will be randomized into two arms, one group will receive conventional treatment with oral mifepristone followed by misoprostol vaginally and another group will receive letrozole for three consecutive days followed by misoprostol vaginally in an attempt to terminate the pregnancy medically. Mean duration of induction to expulsion of product of conception and rate of complete abortion will be compared in two groups.

Nct (2022). "Comparison of Fluoxetine Versus Citalopram Therapy to Control Postmenopausal Vasomotor Syndrome." ClinicalTrails.gov.
	Women's reproductive life goes through a senescence process called transition to menopause, which generates an imbalance in estrogenic hormonal regulation that is more evident between the fifth and sixth decades of life. This condition allows the passage from an active reproductive stage to an inactive one, which triggers an adaptative physiological response to the reduction of estrogens. However, the progressive depletion of estrogen levels causes clinical signs and symptoms in the central nervous system, metabolism, musculoskeletal apparatus, urogenital system, and skin. These symptoms lead to disability, work absenteeism, and health costs, affecting the quality of life of women in this stage. Vasomotor symptoms are the main clinical manifestation for which women seek treatment. Vasomotor syndrome (VMS) occurs in 75 to 80% of all women. The first‐line management of menopausal symptoms is hormone replacement therapy (HRT). However, some patients present adverse effects or contraindications for using it. The aim of this study was to determine the efficacy of the citalopram for treating menopausal symptoms in Mexican women with vasomotor syndrome (VMS) and urogenital syndrome. This study was a prospective randomized clinical trial, where 91 post‐menopausal participants with severe baseline scores on the Menopause Rating Scale (MRS) were randomly selected and treated with citalopram (n=49) or fluoxetine (n=42). Changes from baseline MRS score at three and six months of treatment were evaluated. Participants were randomly assigned to groups before each consult. Randomization was done using RAND and RANK functions from Excel‐Word to generate unique random numbers for every participant´s ID. Fluoxetine is the Gold Standard treatment in Mexico, whereby it was used as the control medication. Loading doses of citalopram 20 mg orally or fluoxetine 20 mg orally were administrated. Statical analysis was performed using PAST 3.0 and GraphPad Prism 8.4.3. software. Some statical parameters, such as arithmetic median (µ), standard deviation (S.D.), and Hazard ratio, were calculated using Excel‐Word. Graphics were constructed with GraphPad Prism 8.4.3. Tables and Forest plots were done in Excel‐Word. Odds ratio (OR), Relative Risk (RR), and chi‐squared were calculated with PAST 3.0 software. The assigned α value for this study was <0.05.

Nct (2022). "Comparison of Letrozole With Lerociclib Versus Letrozole With Placebo Control in Patients With Advanced/Metastatic or Recurrent, Grade 1 or Grade 2 Endometrial Cancer." ClinicalTrails.gov.
	This is a randomized, double‐blinded, placebo‐controlled Phase 3 clinical trial to compare the combination of lerociclib (administered at 150 mg twice a day (BID) with letrozole (administered at 2.5 mg once a day (QD) to that of placebo with letrozole (2.5 mg QD) in female participants with Grade 1 or Grade 2 (ie, low‐grade histology) endometrioid endometrial cancer (EC) and advanced/metastatic or recurrent disease. The study population will consist of female participants with endometrioid EC who are treatment‐naïve in the advanced/metastatic setting (ie, the first‐line [1L] population). Participants may have received prior adjuvant chemotherapy/chemoradiation for localized disease if the adjuvant therapy was administered ≥ 6 months prior. All participants must also be naïve to prior endocrine therapy for EC, and confirmed as medically postmenopausal to be eligible. The study will comprise a Screening Period of up to 28 days in duration; a Study Treatment Phase; a Safety Follow‐up Period spanning the time of study treatment discontinuation‐including discontinuation due to confirmed disease progression, as applicable‐through 28 days after the participant's last dose of any study intervention or the start of subsequent anticancer therapy (whichever occurs first); and a Survival Follow‐up Period that will continue until the participant's death or until at least 50% of all study participants have died (whichever occurs first). While receiving their randomized assigned study treatment, participants will undergo imaging assessments via computed tomography (CT) of the chest/abdomen/pelvis with contrast‐ or, if CT is medically contraindicated (eg, due to iodine allergy), via magnetic resonance imaging (MRI) with gadolinium‐every 8 weeks for the first 12 months and then every 12 weeks thereafter.

Nct (2022). "Comparison of the Euploid Rate of Blastocyst Between PPOS and GnRH Antagonist Protocol in Women With PCOS Undergoing PGT-A." ClinicalTrails.gov.
	This randomized trial aims to compare the euploid rate of blastocysts between PPOS (progestin‐primed ovarian stimulation) and GnRH (gonadotrophin releasing hormone) antagonist protocols in patients with PCOS (polycystic ovary syndrome) undergoing PGT‐A (preimplantation genetic testing for aneuploidy). Infertile women with PCOS will be recruited for study after explanation and counseling if they fulfill the inclusion criteria and do not have the exclusion criteria. Eligible women will be randomised into one of the two groups: Antagonist group: Women will receive antagonist once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger. PPOS group: Women will receive oral MPA (medroxyprogesterone acetate)10mg qd from Day 3 till the day of ovulation trigger. The primary outcome is the euploidy rate of blastocysts.

Nct (2022). "A Crossover Bioequivalence Study of Olaparib Tablets, 150 mg (Lek Pharmaceuticals d.d.) and Lynparza® (Olaparib) Tablets 150 mg (AstraZeneca Pharmaceuticals LP), in Patients With BRCA Mutated Ovarian Cancer, Recurrent Ovarian Cancer or Metastatic Breast Cancer." ClinicalTrails.gov.
	This is a two‐way crossover bioequivalence study between test and reference product in patients diagnosed with BRCA mutated ovarian cancer, recurrent ovarian cancer or metastatic breast cancer. Patients will be enrolled after providing written informed consent and treatments will be allocated to patient by carrying out randomization using statistical techniques. Patients that are already on a stable dose of Lynparza® (olaparib) tablets and have met the eligibility criteria will be directly randomized for participation in the study. After randomization patients will receive either test or reference product in a crossover manner based on the randomization schedule. Patients will receive the dose of 300 mg twice daily for 16 days in a crossover design. In period‐I (Day 1 to Day 8), patients will receive either Test product or Reference product for 8 days based on the randomization schedule. In period‐II (Day 9 to Day 16), patients will be switched to the other product for a second period of 8 days.

Nct (2022). "Didroxyprogesterone Promotes Natural Pregnancy in Infertile Patients With Endometriosis." ClinicalTrails.gov.
	Female patients aged 22‐35 who had been diagnosed with mild to moderate endometriosis by laparoscopic surgery and had undergone surgical treatment and fertility index (EFI) score ≥5 were stratified and randomized at each branch center. The study subjects were first stratified according to EFI score, which was divided into three levels: 5‐6 points, 7‐8 points and 9‐10 points. Then the patients were divided into 2 groups in stratification according to the segmented random method. ① Dydrogesterone group: the first postoperative menstrual cycle began on the 14th to 27th day of each menstrual cycle, dydrogesterone 10mg bid oral administration, planned to use 6 menstrual cycles (if the patient conceived naturally during the medication, the drug could be stopped), and instructed the patient to try pregnancy, observation period was 12 postoperative menstrual cycles; ② Control group: postoperative medication was not used to guide patients to try pregnancy, and the observation period was 12 menstrual cycles after surgery. The subjects should be followed up for a maximum of 6 times, respectively within the first month after surgery, the first menstrual cycle D7‐13 after surgery, the fourth menstrual cycle D7‐13 after surgery, the seventh menstrual cycle D7‐13 after surgery, the 13th menstrual cycle D7‐13 after surgery, and 1‐2 months after pregnancy termination. Outcome measures: ① Pregnancy status; ②EM symptoms and recurrence related indicators: VAS score, physical examination, CA125, gynecological B‐ultrasound examination results; ③ Drug safety assessment: AMH, blood routine examination, liver and kidney function, and the patient's combined drug use and possible drug‐related adverse reactions were recorded.

Nct (2022). "Does Virtual Reality Technology Reduce Pain and Anxiety During Outpatient Hysteroscopy?" ClinicalTrails.gov.
	BACKGROUND Hysteroscopy is a very common gynaecological procedure where a camera attached to a thin scope is passed into the uterus via the vagina and cervix in order to obtain views of the inside of the uterus. Hysteroscopy is used for the diagnosis and management of a variety of benign and conditions as well as the diagnosis of uterine cancer. It can be performed under general anaesthetic or in an outpatient setting without formal anaesthetic. The latter has several advantages when compared to hysteroscopy with general anaesthesia as it avoids the additional risk of general anaesthesia, has a quicker recovery time, shorter hospital stay and reduced cost. Outpatient hysteroscopy (OPH) is generally well tolerated although some women will experience significant pain and pain is one of the most common reasons for failure to complete the procedure. As pain is one of the leading reasons for procedure failure, finding ways to reduce pain and anxiety is of critical importance. The optimal method of controlling pain and anxiety during outpatient hysteroscopy is poorly understood and hotly debated. Options include sedation, local anaesthetic, analgesics including paracetamol, non‐steroidal anti‐inflammatory medication, opioids, Entonox and various distraction techniques. There is a wide variation of clinical practice between different units within the UK due to a paucity of good quality evidence informing best practice. Conventional therapy, as recommended by the Royal College of Obstetricians and Gynaecologists, involves the use of simple pain killers taken prior to the procedure and sometimes local anaesthetic during the procedure if dilatation of the cervix is required (RCOG 2011). Virtual reality (VR) technology is a relatively new and promising technology which if used as a distraction technique, may be able to reduce pain and anxiety experienced from a wide range of medical procedures. Virtual reality (VR) is a human‐computer interface that provides users with various physical sensations (e.g., visual, haptic, auditory) to increase realism in the virtual world (Seth et al. 2011). This heightened sense of realism produces a phenomenon known as "presence," which refers to the user's authentic experience of being in the virtual world as a result of visual or auditory displays generated by a computer (Barfield and Hendrix 1995). VR's ability to provide users with highly realistic immersive experiences can be used to for a variety of medical indications including distraction from uncomfortable or painful procedures. To date VR has been used in a wide variety of inpatient and outpatient clinical scenarios to reduce pain and anxiety including simple blood tests, ENT procedures and minor gynaecological procedures such as hysterosalpingograms (Chan et al 2018, Wang et al 2020 and Ahmadpoura et al 2019). However, currently, to the best of our knowledge, there is only one relatively small‐scale trial investigating the use of VR in an outpatient hysteroscopy setting (Deo et al 2020) meaning further studies are urgently needed to clarify the situation. RATIONALE FOR CURRENT STUDY The purpose of this study would be to determine if the use of VR technology can reduce pain and anxiety experienced by patients during outpatient hysteroscopy procedures when compared to standard pain management. The optimal method of controlling pain and anxiety during outpatient hysteroscopy is poorly understood and there is a wide variation in clinical practice. This study aims to test whether VR technology could reduce pain and anxiety as a relatively simple and safe adjunct to conventional pain management. Although VR has been used in a variety of clinical settings to date, there is only one previous study investigating the use of VR in an outpatient hysteroscopy setting (Deo et al 2020). This existing trial established that the use of VR is feasible in the OPH setting and that it was effective with significant improvements in patient reported anxiety and pain scores compared to conventional pain management. However, as the authors themselv acknowledge, it involved relatively small numbers (20 patients in control and intervention group respectively). The rationale of this study would be to build upon this evidence by performing the first large scale adequately powered randomised control trial of the use of VR technology in this setting. The study team hypothesises that the use of VR technology will significantly improve pain and anxiety when compared to conventional pain management. Finding additional low risk ways of improving pain and anxiety during OPH is of critical importance in order to improve patient experience and the success rate of the procedure as pain is a major reason for unsuccessful OPH procedures. 2. STUDY OBJECTIVES The primary objectives of this study are to determine if: 1. VR technology can reduce pain during outpatient hysteroscopy? 2. VR technology can reduce anxiety during outpatient hysteroscopy? The secondary objectives of this study are to determine if: 1. The use of VR technology feasible during outpatient hysteroscopy? 2. The use of VR during outpatient hysteroscopy reduces the procedure failure rate? 3. The use of VR increases the outpatient hysteroscopy appointment time? STUDY DESIGN The study design is an unblinded randomised controlled trial. This study design was chosen as it will provide the best quality of evidence with reduced bias compared to other study designs. A randomised controlled trial is also very feasible in this scenario. Neither the researchers nor the participants will be blinded as to which study arm they are in, as it would be impractical to do so with a VR headset used in the intervention group. The study will be adequately powered with a power calculation based upon findings from previous studies, meaning at least 40 patients will be included in each arm (at least 80 patients in total). Patients will be randomly allocated by computer allocation to either the intervention or the control group. The intervention group will undergo OPH with standard care plus the use of VR technology administered through a headset with the option of wearing headphones (at the patient's discretion) or having the accompanying sound played aloud. The control group will undergo outpatient hysteroscopy with standard care. Standard care in this unit is in line with the RGCOG guidelines and involves advising patients to take ibuprofen and/or paracetamol one hour prior to their procedure unless there are contraindications. Local anaesthetic intracervical block is used at the discretion of the operator and is usually used if dilatation of the cervix is required. The primary outcome measure will be the reported NRS (numeric rating score) score which is validated score to assess pain and anxiety levels with values from 0‐11. The patient will be asked to fill out the NRS score prior to the hysteroscopy and following the hysteroscopy prior to leaving the clinic. Secondary outcome measures will be length of procedure, complication rate, reported side effects, procedure completion, hysteroscopy findings and type of procedure performed (for example if purely diagnostic or if any operative procedures are performed). Participants will be recruited from the general gynaecology clinics. Only patients who have already opted to undergo outpatient hysteroscopy will be invited to take part in the study and they will be made aware of the study at the time of the clinic appointment or shortly after. Interested parties will then be contacted by the research team to discuss the study in more detail at a time which is convenient for the patient. Written consent to enter the study will be sought from the participant in advance of their procedure and only after a full explanation has been given. The patient will be offered a study information leaflet. Whilst waiting for their hysteroscopy procedure, the patient will be offered a face‐to‐face appointment with a member of the research team to discuss the study and sign the written consent form if they wish to participate in the study. If it is more convenient for the patient, and to avoid unnecessar dditional appointments for the patient, they may prefer to discuss the study and go through the consent by phone before confirming consent on the day of the procedure. Patients will have time to consider whether to take part in the study prior to their procedure day and will be informed that they can withdraw consent for participation in the study at any time. Participating or not participating in the study will have no effect on the timing of the outpatient hysteroscopy or the type of procedure performed. Patients will have the opportunity to choose which virtual reality scenario they wish to experience during the procedure (choice of 4 scenarios from beach, space, underwater and zen four seasons). At the time of their hysteroscopy. The patient will fill out the pre‐procedure NRS score prior to entering the hysteroscopy room. The patient will then enter the outpatient hysteroscopy room where there will be the hysteroscopy team consisting of the lead hysteroscopist and the assistant, and also a single member of the research team who will have taken the study consent from the patient prior to their procedure. Following discussion with the hysteroscopist as usual, the patient will prepare for the procedure and position themselves on the procedure couch. Once comfortable, the member of the research team will help the patient to put on the VR headset (See appendix 1), and if the patient wishes, headphones. The virtual reality software will then start running and is controlled by the research team member, the software will run for the length of the procedure. The hysteroscopy team will be preparing the equipment as the virtual reality software is running. The member of the research team will remain in the room throughout the procedure to troubleshoot any issues with the headset or software and if necessary to stop the VR program. Following completion of the procedure the patient will fill out a NRS score prior to going home. The VR software involves breathing exercises, relaxing music and a distracting immersive walk through a virtual environment. The scenario will be started and subsequently controlled by a member of the research team operating a tablet device. The hysteroscopy team will perform the procedure in exactly the same way as they would normally and any clinical decisions regarding potential procedures such as polypectomy, discontinuing or proceeding with the hysteroscopy will be made by the hysteroscopy team along with the patient in the usual way without any input from the research team member. Maintaining appropriate clinical hygiene is of critical importance as the same headset will be used for different patients. The headset can be easily and effectively cleaned between use and the manufacturer (VR medical) provides a recommended cleaning regimen which we will use for the trial. After use, the VR device and controller should be cleaned with a damp microfibre cloth and disinfectant wipe, both the parts that have been in contact with the skin and the headbands. The timetable for the project is expected to run as follows. Three months for preparation and obtaining ethical approval. Recruitment is expected to start following this and we would expect to obtain the required number of participants by 3 months based on the average referral rate for outpatient hysteroscopy in the unit being 150 patients per month and a 20% study participation rate. Data analysis and preparing the final report would take a further 3 months. Results will be recorded onto a pseudoanonymised database. Information will be collected from patients notes and imaging reports. Each patient will be allocated a study number and for each the following will be recorded: Age Parity Symptoms and duration Past medical history and co‐morbidities BMI Previous surgery Current medication and medication used within the last 6 months Pain NRS (numeric rating score) Anxiety NRS Length of hysteroscopy procedure Time in Outpatient Procedure room Procedure successfully completed (or not) and reason for failure if appropriate Complications Hysteroscopy find n s Type of hysteroscopic procedure performed STUDY OUTCOME MEASURES The primary outcome measure will be the reported NRS (numeric rating score) score which is validated score to assess pain and anxiety levels with values from 0‐11. The patient will be asked to fill out the NRS score prior to the hysteroscopy and following the hysteroscopy prior to leaving the clinic. Secondary outcome measures will be length of procedure, complication rate, reported side effects, procedure completion, hysteroscopy findings and type of procedure performed (for example if purely diagnostic or if any operative procedures are performed).

Nct (2022). "Donepezil Prevents Urinary Retention After Extensive Total Hysterectomy." ClinicalTrails.gov.
	This study hypothesized that donepezil could effectively reduce the incidence of urinary retention in cervical cancer patients after extensive total hysterectomy. A total of 108 patients with cervical cancer who underwent abdominal radical hysterectomy in our department from June 1, 2022 to May 31, 2023 were randomly divided into two groups, the experimental group (n = 54) and the control group (n = 54). The incidence of postoperative urinary retention and adverse drug reactions were compared between the two groups. A. Screening accords with the standard set of subjects, abdominal widely whole palace resection, BiXing random grouping, experimental group from the first day after oral donnelly, pp every night before going to bed together 5 mg, two groups of patients with the rest of the regular place Agreement (including antibiotics to 48 h, postoperative indwelling catheterization, perineum wipe to wash the bid, wound dressing, etc.); B. The catheter was removed and the residual urine was measured 14 days after operation. The residual urine was ≤100ml, and the catheter was successfully removed. The patients in the experimental group stopped taking the drug, and the residual urine was > 100ml. C. Residual urine of patients with urinary retention was measured again 14 days later, and the residual urine was ≤100ml. Patients in the experimental group stopped the drug, and the residual urine was > 100ml. Intermittent catheterization was continued, and patients in the experimental group continued to take the drug until the residual urine volume was ≤100ml. D. This cycle was carried out until the residual urine volume of the last enrolled patient was less than 100ml. The incidence of postoperative urinary retention and adverse drug reactions were compared between the two groups.

Nct (2022). "Dual Trigger" in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome." ClinicalTrails.gov.
	While the use of GnRH‐a trigger has nearly eliminated the risk of OHSS, several studies have shown that this strategy may be associated with poorer IVF outcomes after a fresh embryo transfer (Engmann et al., 2008; Galindo et al., 2009; Melo et al., 2017; Sismanoglu et al., 2009; Youssef et al., 2014). These findings may be partly explained by an inadequate LH surge, following a GnRH‐a trigger, and raises two separate concerns. The first concern is whether an inadequate LH surge can have an detrimental effect on luteal support following a fresh embryo transfer. The corpus luteum requires constant LH stimulation, during implantation and early gestation, in order to optimize endometrial receptivity via the production of progesterone. The second concern is whether a suboptimal LH surge can reduce the number or quality of mature oocytes retrieved during a treatment cycle. Immature oocytes will not fertilize invitro and, therefore, can decrease a woman's overall success rate with IVF. Based on this second premise, another strategy was developed whereby a "dual trigger", using a combination of a GnRH‐a and a lower dose of hCG (1,500 IU), is used to help maximize the number of "mature eggs" retrieved during an IVF cycle without increasing the risk of OHSS. Two recent retrospective studies have evaluated the administration of a "dual trigger" with GnRH agonist in combination with low‐dose hCG (1,000 IU), compared to GnRH agonist alone (O'Neill et al., 2016; Griffin et al., 2012). Both studies revealed a significant improvement in the number of mature oocytes retrieved between treatment and controls (Griffin et al., 2012). While these findings are promising, it is important to note that oocyte maturity does not equate to embryo potential. Therefore, whether the use of a "dual trigger" improves embryo development and competency, thus increasing a patient's success rate, remains to be determined.

Nct (2022). "Educating Women About Pelvic Floor Disorders During Pregnancy." ClinicalTrails.gov.
	Pelvic floor disorders (PFDs) are common and significantly affect the quality of life of many women as they age. Pregnancy has been identified as a major risk factor for developing PFDs later in life. Educating women about PFDs is essential to ensuring that they present to care in a timely manner. No study has investigated different education tools during pregnancy. The proposed study is a randomized controlled trial in pregnant patients comparing two educational tools: written materials about PFDs versus an educational workshops led by pelvic floor physical therapists (PFPTs). Pregnant patients will be recruited in the first and second trimester and randomized at that time. Knowledge will be assessed at baseline and again 6 weeks postpartum using the validated Prolapse and Incontinence Knowledge Questionnaire. Secondary outcomes will be evaluating referral patterns to urogynecology and to PFPTs from general OBGYNs and assessing any pelvic floor symptoms with the pelvic floor disability index (PFDI‐20) at baseline and at 6 weeks postpartum.

Nct (2022). "The Effect of Acupressure and Mindfulness to Cope With Premenstrual Syndrome (PMS) on PMS and Quality of Life." ClinicalTrails.gov.
	Premenstrual syndrome (PMS) is a gynecological condition consisting of physical, psychological and behavioral symptoms that occur 7‐10 days before menstruation and end with the onset of menstruation. Symptoms are divided into three groups as mild, moderate and severe. The prevalence of PMS is reported to be 47.8% on average worldwide. About 20% of these are severe symptoms and may affect women's daily activities, while 27.8% are mild to moderate symptoms. PMS reduces daily activities, sleep quality and cognitive functions of women of reproductive age. However, it can negatively affect women's health, interpersonal relationships, academic performance, attendance at work and school, and quality of life. In the treatment of PMS, 80% of women prefer non‐pharmacological treatment. Non‐pharmacological methods such as lifestyle changes, music, massage, yoga, aromatherapy, reflexology, homeopathy, cognitive behavioral therapy, emotional liberation technique, reiki, acupuncture, mindfulness, acupressure methods are frequently used in the treatment of PMS. The population of the research consists of 1006 female students, 598 of whom are studying at İnönü University Faculty of Nursing and 408 female students studying at Bartın University Faculty of Health Sciences. The sample of the study was determined by power analysis with an effect size of 0.22, a confidence interval of 0.95 determined by an error level of 0.05, a sample size of 90 for each group (90 in the acupressure group, 90 in the mindfulness group, and 90 in the control group) with 0.95 universe representation power. group 90) female students with a total of 270 PMS were determined. However, it was decided to include an additional 10 students for each group, taking into account the losses that may occur during the study. In the study, 100 acupressure, 100 mindfulness and 100 female students formed the control group. In the study, which university would be included in the control and experimental groups was determined by drawing lots. The draw was made blind by an academic independent of the research. As a result of the lottery, the control group of the research was formed by the students of İnönü University Faculty of Nursing, and the experimental groups were students studying at the Faculty of Health Sciences of Bartın University. Students from each faculty to be included in the study were determined using a computer‐assisted simple random sampling method. Students in the experimental and control groups were determined according to an algorithm created by a computer program called Research Randomizer. For the control group, 598 female students in İnönü University Nursing Department, numbers from 1 to 598 were randomly divided into a single set.For the experimental groups, 408 female students from the Faculty of Health Sciences of Bartın University were randomly divided into two sets (100 acupressure, 100 mindfulness), numbers numbered from 1 to 200. Which set will be acupressure and mindfulness group was determined by drawing lots. A research‐independent academician made the selection blindly. As a result of the draw, it was determined that the first set was the acupressure group, and the second set was the mindfulness group. The assignment of the students to the experimental and control groups was made using the simple randomization method. Students were sorted by student number before randomization. Experimental and control groups were determined by the order given by the computer program Research Randomizer. The students who scored 110 and above were included in the study, after which the PMSS scale was applied to the determined students. In the study, it was accepted that 338 students who scored 110 and above from the scale experienced PMS. In the study, data were collected with the Participant Information Form, PMSS and WHOQOL‐BREF. The acupressure group was asked to apply acupressure two days a week for 12 weeks, a total of 24 times. In the mindfulness group, 8 weeks of Conscious Awareness Stress Reduction Program was applied, after wh h the students were asked to practice mindfulness for 3 cycles. Students in both experimental groups were asked to stop the practices after acupressure and mindfulness practices. PMSS and WHOQOL‐BREF were applied to both experimental and control groups as an intermediate test 12 weeks after the pre‐test and a post‐test 24 weeks later.

Nct (2022). "Effect of Acupuncture Combined With Biofeedback Electrical Stimulation on SUI." ClinicalTrails.gov.
	Objective: To investigate the clinical efficacy of acupuncture combined with biofeedback electrical stimulation on female stress urinary incontinence. Methods: 90 patients diagnosed in a hospital from January 2020 to January 2021 were randomly divided into three groups A, B and C, and group A was treated with biofeedback electrical stimulation, 3 times a week for 30 minutes for 15 times. Group B used acupuncture treatment, including Guanyuan, Qihai, Zhongji, Zusanli, Sanyinjiao and Yinlingquan, once a day, Monday to Friday, 30 minutes each, a total of 10 times. Group C was treated with acupuncture combined with biofeedback electrical stimulation. All three groups were combined with pelvic floor muscle training. After treatment, the changes in class I, II muscle fiber, ICI‐Q‐SF score, and urine leakage in the 1h pad test were compared.

Nct (2022). "Effect of Aerobic Exercise on Polycystic Ovary Syndrome." ClinicalTrails.gov.
	The development of Polycystic Ovary Syndrome has been linked to chronic low‐grade inflammation (PCOS). In this context, the current study looked into the effects of aerobic exercise on IL6, TNF, and C‐reactive protein (CRP) in PCOS women. This was a randomized clinical trial including 40 females diagnosed with PCOS who were between the ages of 25 and 35. The participants were divided into two groups, each with an equal number of individuals: aerobic exercise (AEM) and Metformin (M). At baseline and after 12 weeks of intervention, participants' levels of IL6, TNF, and CRP were measured.

Nct (2022). "Effect of Albumin-bound Paclitaxel Plus Carboplatin Compared With Paclitaxel Plus Carboplatin in Patients Receiving Neoadjuvant Chemotherapy for Advanced Ovarian, Fallopian Tube or Peritoneal Cancer: a Phase 2 Single Center Clinical Trial." ClinicalTrails.gov.
	Neoadjuvant chemotherapy (NACT) is an important option for patients with advanced ovarian cancer. Paclitaxel plus carboplatin is the first‐line regimen for ovarian cancer NACT patients. However, the efficacy of NACT is controversial, how to improve the efficacy become an urgent problem to be solved in the treatment of ovarian cancer. It has been confirmed that the dose‐intensive paclitaxel combined carboplatin regimen can improve the prognosis in Asian patients with advanced ovarian cancer. However, this protocol has a low rate of complete tumor remission after NACT (4%) with toxicities and high probability of severe hypersensitivity reactions. Albumin‐bound paclitaxel has the characteristics of tumor targeting, low allergenicity. We propose that dose‐dense albumin‐bound paclitaxel (ddnab‐paclitaxel) (100 mg/m2, days 1, 8, and 15) combined with carboplatin (AUC = 5 days 1, 4 weeks) regimen may be superior to the paclitaxel plus carboplatin regimen. We conducted this Phase II randomized controlled study to testify the efficacy of dd‐nab paclitaxel. 57 stage IIIC‐IV patients with high‐grade epithelial, fallopian tube, and peritoneal cancer who are unable to undergo optimal cytoreduction and receive NACT after tumor biopsy will be recruited. The regimen for the study group is albumin‐bound paclitaxel (100 mg/m2, days 1, 8, and 15 doses) combined with carboplatin (AUC = 5 day 1, 4 weeks), while patients in the control group use paclitaxel (175 mg/m2, day 1) combined with carboplatin (AUC=6, day1). Interval debulking surgery(IDS) will be performed within 3‐4 weeks after 3 cycles of NACT. The primary endpoint is the proportion of Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints are progression‐free survival(PFS), overall survival(OS) and the rates of complete resection and adverse events(AEs).

Nct (2022). "The Effect of Art on Premenstrual Syndrome Symptoms." ClinicalTrails.gov.
	First of all, ethics committee approval will be obtained by applying to the Non‐Interventional Ethics Committee of the Rectorate of Kütahya Health Sciences University for the research. Then, written permission will be obtained from the Dean of the Faculty of Health Sciences of Kütahya Health Sciences University and the Department of Midwifery. In addition, written consent was obtained for the PMSS to be used in the research. At the first stage, the researcher will apply the research forms to all midwifery students willing to participate in the study without using any sampling method. The forms will be applied to volunteer and willing students after the lesson, in an appropriate classroom, by explaining the research and purpose. It is anticipated that the filling time of the forms will be 15‐20 minutes on average. Then, all data will be evaluated in the SPSS program and randomization will be provided among the students who meet the inclusion criteria. Participants will be evaluated in two groups. One of the groups is the study group, where artistic techniques will be applied, and the other group is the control group, which will continue their routine coping habits for PMS. Participants will be randomly assigned to one of two groups using the www.randomizer.org program. Students in the study group (35) will do group work that will last for 30‐35 minutes, one day a week, for 8 weeks, with the Artistic Techniques Education Directive prepared by the researcher holding a certificate on artistic techniques in parallel with the education they received. There is no intervention or therapy involved here. Art is used as an expressive technique, and these techniques enable students to better understand and interpret their own emotions at the end of their activity. The researcher will only apply the techniques and pose non‐directive questions. At the same time, these techniques raise awareness. At the end of 8 weeks, students will be reassessed with PMSS. Students in the control group (35) will not be subjected to any application, and in parallel with the study group, they will be told to continue their routine habits regarding PMS. At the end of 8 weeks, students will be reassessed with PMSS.

Nct (2022). "The Effect of ASTARTE™ on Recurrent Urinary Tract Infection." ClinicalTrails.gov.
	Urinary tract infection (UTI) is one of the most common infections, contributing to increased antibiotic consumption and high costs. Women are often developing UTI due to the anatomically short distance from the rectum opening to the urethra. There is a risk of serious complications associated with pregnancy, where there is an increased risk of developing pelvic inflammatory disease and premature birth. This will in some cases lead to increased risk of maternal and neonatal morbidity and mortality; especially in infection with Streptococcus agalactiae. Recurrent UTI (rUTI) with urease producing microorganisms such as Proteus and Klebsiella will cause an increased risk of developing stones in the urinary tract. Scientific studies suggest that probiotics can be effective dietary supplements reducing the risk factors for the development of infections in the intestine and vagina. Probiotics are non‐pathogenic microorganisms capable of affecting gastrointestinal microbiota with a change in microbiota composition, thus increasing the production of beneficial substances when ingested in appropriate quantities. The consumption of probiotics is not considered to be associated with adverse reactions to humans because they are usually found naturally in e.g. gastrointestinal and vaginal microbiota. A prospective study over 2‐years which is conducted as a randomized placebo‐controlled double‐blind study. In this study the investigators will investigate the effect of probiotics ASTARTE™ ( Lactobacillus crispatus, Lactobacillus rhamnosus, Lactobacillus jensenii, Lactobacillus gasseri) on the composition of bacteria in urine, faces and vagina, and a possible reduction of risk factors for development of rUTI in women (18 to 40 years). The investigators will map the microbiota in the faeces and vagina and examine if there are a relationship between colonization of the urinary tract with pathogens and the composition of the intestinal and vaginal microbiota.

Nct (2022). "The Effect of Dienogest vs. Norethindrone Acetate Treatment in Endometriosis." ClinicalTrails.gov.
	The aim of this observational drug study was to evaluate the patients with medical treatment indications who applied to Bursa Uludağ University Medical Faculty Hospital, Department of Obstetrics and Gynecology, Endometriosis and Chronic Pelvic Pain Outpatient Clinic, during the application of 2 different progesterone protocols with proven efficacy, which are currently recommended for routine use, with 6‐month periods and three doses. To compare the effects of different progesterone‐derived protocols in use and their effects on treatment effectiveness and recurrence by evaluating ultrasonographic parameters, laboratory parameters, and numerical scoring system scores of patients on chronic pain symptoms (dysmenorrhea, dyspareunia, dysgeusia, and chronic pelvic pain) at different visits. It was designed as a one‐time prospective, randomized observational study. Patients who applied to the Endometriosis and Chronic Pelvic Pain Polyclinic and were evaluated by the relevant faculty members and received medical treatment indications will be randomly assigned to one of the two treatment protocols used as single‐digit 'norethindrone acetate' and double‐digit 'dienogest' according to the last digit of the current hospital protocol numbers in the system. At the time of the first application, the patients will be recorded in the patient files together with their personal and demographic data, the duration of the previous treatments and the reasons for their discontinuation, the operation notes, and centers of their previous surgeries due to endometriosis, if any. Patients will be evaluated with ultrasonographic evaluations and detailed physical examinations, and laboratory tests. In the ultrasonographic evaluation, uterine contours, presence of adenomyosis, detailed evaluation of the adnexal area, if there is the presence of endometrioma, its size, and the evaluation of the Douglas cavity will be made in detail. Physical examination includes vaginal and rectal examination, and tenderness and nodular appearance will be evaluated. Laboratory parameters include complete blood count, biochemical parameters, tumor markers, and anti‐mullerian hormone levels, which we routinely check in the endometriosis outpatient clinic. It will be evaluated and recorded at each visit. Patients will be questioned for existing dyspareunia, dysmenorrhea, dysgeusia, and chronic pelvic pain. Grades will be written by asking the patients to give a score between 1‐10 with the numerical scoring system for their existing pain complaints. In addition, accompanying gastrointestinal and genitourinary symptoms will be noted in the patient's file. Patients will be reassessed at 6 and 12 months while on treatment with progestins given according to protocol numbers. In addition, at each visit, patients will be evaluated for possible side effects of medical treatment and recorded. In terms of side effects, patients will be asked to give points between 1‐10 with the numerical scoring system. Any other side effects will be recorded in the patient file. The information of these records will be taken from the file by the responsible worker after each visit and recorded in the study forms. The study supervisor is not authorized to determine or change the patient's treatment protocol. In statistical analysis, a comparison between the groups will be made with the Kruskal Wallis test as a non‐parametric test using the SPSS‐22 program. P value <0.05 will be considered statistically significant. 4. STUDY POPULATION File analysis of all patients between the ages of 18‐40 who applied to our center with the diagnosis of endometriosis and met the inclusion criteria will be performed. CRITERIA FOR INCLUSION ‐ Patients aged between 18 and 40 who applied to our Endometriosis and Chronic Pelvic Pain Outpatient Clinic ‐ Patients who do not want pregnancy ‐ Patients with a diagnosis of endometriosis and a medical suppression indication due to pain. EXCLUSION CRITERIA ‐ Patients who are contraindicated to use progesterone ‐ Patients who have developed n allergic reaction to the progesterone preparations used and the active ingredients in it ‐ Patients with pelvic inflammatory disease accompanying endometriosis ‐ Patients diagnosed with uterine malformation with previous surgery ‐ Patients with obstructive genitourinary and gastrointestinal symptoms and indication for surgical treatment STUDY CENTER Bursa Uludağ University Faculty of Medicine Hospital, Department of Obstetrics and Gynecology Endometriosis and Chronic Pelvic Pain Polyclinic DETERMINATION OF STUDY POPULATION It is planned to recruit patients between the ages of 18‐40 who receive medical treatment indications in Bursa Uludağ University Medical Faculty Hospital, Department of Gynecology and Obstetrics Endometriosis and Chronic Pelvic Pain Polyclinic. DIAGNOSIS AND TREATMENT PROTOCOL The files of patients who applied to Bursa Uludağ University Gynecology and Obstetrics Department Endometriosis and Chronic Pelvic Pain Polyclinic and started medical treatment will be examined. The progesterone treatment protocols routinely used in the Endometriosis and Chronic Pelvic Pain Outpatient Clinic are as follows; 1. The use of progesterone, which is started on the second day of the menstrual cycle and continued uninterruptedly (norethindrone acetate 5 mg tablet p.o. 1x1 in posology) 2. Progesterone use, which is started on the second day of the menstrual cycle and continued uninterruptedly (dienogest 2 mg tablet p.o. 1x1 in posology). Apart from the routine operation of the clinic, no non‐routine procedures will be performed in the study. The study supervisor does not have the authority to be involved in the treatment and change the protocol. It will only observe and analyze data of treatment protocols initiated from the file. MATERIALS AND METHODS Patients who applied to the Department of Obstetrics and Gynecology Endometriosis and Chronic Pelvic Pain Polyclinic and received medical suppression treatment indications were included in the study. No changes will be made in the treatment and follow‐up protocols of the patients for the purpose of the study. Patients who are started on medical treatment are routinely called for follow‐up at 6‐month intervals. At the beginning of the treatment, at the 6th and 12th months of the treatment, all patients will be routinely visited. Patients will not be included in the evaluation of additional controls and examinations for the purpose of the study. The current evaluations of the patients in treatment will be recorded. Patients who are on the protocol of 2 different progesterone derivatives recommended by the guidelines and applied in our clinic will be compared among themselves in terms of laboratory parameters, ultrasonographic evaluations, and numerical scoring systems for chronic pain symptoms, and the effects of these values on treatment effectiveness and recurrence outcomes will be evaluated and the records in the patient files will be examined. The research will be carried out by collecting data from patient files, and the study we have done will not cause any change in the current treatment of patients. DURATION OF STUDY The duration of the study is 12 months.

Nct (2022). "The Effect of Digital Literacy Education Given to Postmenopausal Women on Health Literacy and Quality of Life." ClinicalTrails.gov.
	Purpose of the Study: This study was planned as a randomized controlled experimental study to examine the effect of digital literacy education given to postmenopausal women on health literacy and quality of life. Data Collection: The data will be collected by the researcher by face‐to‐face interview method in a total of 5 sessions, each session of 30 minutes. Statistical Methods to be Used: SPSS program will be used in the analysis of the obtained data. The conformity of the data to the normal distribution will be examined by considering the Shapiro‐Wilk test; Parametric methods will be used in the analysis of normally distributed variables, and non‐parametric methods will be used in the analysis of non‐normally distributed variables. Independent‐Samples T test, Mann‐Whitney U (Exact) test and T test for Dependent Groups, Wilcoxon test will be used in the comparison of 2 independent groups. PearsonCorrelation, Spearman'srho tests will be used to examine the correlations of the variables with each other. Comparison of categorical data will be tested with PearsonChi‐Square and FisherExact tests.

Nct (2022). "The Effect of E-health Video Towards Enhancing Cervical Cancer Screening." ClinicalTrails.gov.
	The aim of this quasi‐experimental study is to evaluate the women's motivation related to cervical cancer screening. The experiment group will receive the e‐health video KaSEH and brochure as the intervention. Where as, the control group will receive brochure as the intervention. There is three phase of evaluation which are pre‐intervention, intra‐intervention and post‐intervention. The evaluation will be assess using the self‐administered questionnaire based on Protection Motivation Theory. The estimated duration of this quasi‐experiment is six month.

Nct (2022). "The Effect of Emotional Freedom Technique on Premenstrual Syndrome." ClinicalTrails.gov.
	Menstruation is an important process accompanied by physiological and psychological fluctuations covering a long part of a woman's life. Premenstrual syndrome (PMS) is characterized by cyclical repetition of physical, psychological and behavioral symptoms that start one week before menstruation, gradually increasing in severity, and end with menstruation [1‐3]. Presence of at least one of six affective symptoms (anger outburst, depression, anxiety, confusion, irritability, and social withdrawal) and one of four somatic symptoms (abdominal swelling, headache, breast tenderness, and swelling in the extremities) according to the American Association of Obstetricians and Gynecologists (ACOG). It states that if the symptoms disappear 4 days after the onset of the disease, and if it recurs cyclically, it meets the diagnostic criteria of PMS [4]. In studies conducted on PMS in various societies, its prevalence was determined to be in the range of 10‐98% [5‐8]. Although the etiology is not known exactly, the most common view is in the direction of serotonergic dysregulation. It is thought that the level of serotonin negatively affects the severity and intensity of PMS symptoms, and also triggers or exacerbates symptoms such as anxiety, appetite change and restlessness with the decrease in beta endorphin levels [9,10]. According to the severity level in PMS treatment; lifestyle changes (regular exercise, stress avoidance, regular sleep, etc.), combined oral contraceptives, serotonin selective inhibitors and cognitive behavioral therapies can be used [3, 11]. ACOG recommends using non‐pharmacological treatments rather than pharmacological treatments for mild symptoms with psychological predominance [4]. Although it has a history of thousands of years in eastern cultures, it argues that the methods of energy psychology that we have encountered in the last 40 years in western societies and that psychological problems are related to disturbances in the energy fields of the body. According to energy psychology, people are physiological, emotional, mental and behavioral whole and in harmony. When the harmony is disturbed, psychological symptoms occur, and treatment is aimed by regulating the energy frequency by taking initiatives for this [12, 13]. In this context, Emotional Freedom Technique (EFT) is a psychophysiological method that provides easy and fast results to manage the normal energy flow on the energy body of the person [14, 15]. The main purpose of EFT is; It is to transform the negative energy frequency of the person into a positive one by clearing the negative emotions and thoughts that the person has subconsciously created or carried from the past by himself or environmental influences [14]. In the 1980s, thought field therapy, which was applied with strokes/touches to human meridian points with a complex algorithmic order, was simplified by Craig and started to apply with a single algorithmic order, thus EFT emerged [16, 17]. EFT is applied with strokes/touches as a somatic stimulus applied to meridian points, which includes stimulating the subconscious as in cognitive behavioral therapies, accepting a negative situation or emotion as in exposure therapy. It is frequently used in the treatment of psychological symptoms in current studies because it is easy to apply in opening the blockages in the energy body or converting the negative frequency to positive and has a quick result [18]. There are studies showing that EFT has positive effects on variables such as anxiety [14], phobias [15], posttraumatic stress disorder [16] and depression [17]. In the field of women's health, the effects of EFT studies on psychological development and cortisol levels in pregnant women with prenatal loss [18], fear of childbirth [19], dysmenorrhea [20] and postpartum depression [21] The results are extremely positive. In this context, it is thought that the research will contribute to the literature due to the insufficiency of studies examining the effect of EFT application on premenstrual syndrome.

Nct (2022). "The Effect of Hydrogen-rich Water on Premenstrual Symptoms and Quality of Life." ClinicalTrails.gov.
	The aim of this study is to determine the effect of hydrogenated water on premenstrual symptoms and quality of life in students with premenstrual syndrome. Research Hypotheses H1 1 Hydrogenated water consumption reduces premenstrual symptoms in students with premenstrual syndrome. H1 2 Hydrogenated water consumption increases the quality of life in students with premenstrual syndrome. The research will consist of intervention and control groups. Individuals consuming hydrogen‐rich water will be included in the intervention group, whereas individuals consuming normal water will be in the control group. The block randomization method will be used to randomly assign participants who meet the research criteria to the groups. Participants will be provided with hydrogenated water for three cycles.

Nct (2022). "The Effect of Jincaopian Tablets on Chronic Pelvic Pain After Pelvic Inflammatory Disease." ClinicalTrails.gov.
	Chronic pelvic pain is the major sequela of pelvic inflammatory disease and it's a common, burdensome, and costly condition that disproportionately affects women. This multicenter, randomized, double‐blind, dose‐parallel, placebo‐controlled phase II clinical trial is designed to evaluate the efficacy and safety of Jincaopian Tablets in the treatment of subjects with chronic pelvic pain after pelvic inflammatory disease. In this trial, 180 subjects were enrolled and randomized to either "high‐dose Jincaopian Tablets" group, "low‐dose Jincaopian Tablets " group, or the "placebo" group in a 1:1:1 ratio. The treatment period is 12 weeks and the follow‐up period is 4 weeks. The outcome measures of chronic pelvic pain relief in this trial are pain visual analog scale (VAS), modified McCormick scale and SF‐12 Score.

Nct (2022). "The Effect of Local Anesthetic Solution in the Bladder Prior to Botox Injections in the Bladder." ClinicalTrails.gov.
	The aim of the study is to investigate if bladder installed Lidocaine solution have an effect on reported pain during BTX‐A injections compared to placebo. The study participants will be recruited from the existing patient populations enrolled in the BTX‐A program of the tertiary Urogynaecological Clinic of Herlev University Hospital. The participants are randomized to: 1. Active drug: Lidocaine Hydrochloride and Sodium hydrogen carbonate 2. Placebo: Sodium Chloride The study includes 5 study visits: Visit 1: ‐ First treatment day ‐ Randomization ‐ Registration of pre‐treatment pain relief medications: paracetamol, ibuprofen, or other medications. If pre‐treatment pain relief is taken before first treatment, same pain relief should be taken before second treatment day (visit 4) in order to reduce bias ‐ Registration of antibiotic treatment: current antibiotic treatment or long‐term prophylactic antibiotic for prevention of recurrent UTI The participant receives the active treatment or placebo, double‐blinded ‐ The participant is asked to grade the intensity of pain according to VAS score immediately after, and when participant has been dressed after the BTX‐A injections Visit 2 (by telephone): ‐ Phone consultation 1 week after treatment: ‐ The participant's experience on the procedure on a 5‐point ordinal scale: "1‐ very unsatisfied", "2‐ unsatisfied", "3‐ neither unsatisfied or satisfied", "4‐ satisfied", "5‐very satisfied" Side effects: ‐ Questions on symptoms of UTI: dysuria, cloudy urine, pollakiuria, nocturia ‐ Hematuria ‐ Inability to empty the bladder ‐ Other symptoms (Visit 3:) ‐ The participant contacts the Clinic for next treatment approximately 6‐12 months later ‐ Sponsor or investigator from the Urogynecological Clinic reach out for the participant asking on symptoms of UUI if the participant has not contacted the clinic within 12 months Visit 4: ‐ Second treatment day ‐ The participant receives the opposite treatment, still double‐blinded ‐ Registration of pre‐treatment pain relief medications: paracetamol, ibuprofen, or other medications ‐ Registration of antibiotic treatment: current antibiotic treatment or long‐term prophylactic antibiotic for prevention of recurrent UTI ‐ The participant is asked to grade the intensity of pain according to VAS score immediately after, and when participant has been dressed after the BTX‐A injections Visit 5(by telephone): ‐ Phone consultation 1 week after treatment: ‐ The participant's experience on the procedure on a 5‐point scale: "1‐ very unsatisfied", "2‐ unsatisfied", "3‐ neither unsatisfied or satisfied", "4‐ satisfied", "5‐very satisfied" Side effects: ‐ Questions on symptoms of UTI: dysuria, cloudy urine, pollakiuria nocturia, ‐ Hematuria ‐ Inability to empty the bladder ‐ Other symptoms

Nct (2022). "The Effect of Logotherapy on Mental Health in Gynecological Cancer Patients." ClinicalTrails.gov.
	Cancer exposes the individual to challenging situations like lack of knowledge about the treatment process, low/absence of social support, economic difficulties, fear of losing health, changes in roles in society and family, and fear of death. In addition to these situations encountered in all types of cancer, gynecological cancers also negatively affect women's sexuality, fertility, menopause symptoms, and self‐perception, leading to the deterioration of their psychological health. The absence of supportive care against these cancer‐induced adverse conditions causes stress, anxiety, depression, post‐traumatic stress disorder (PTSD), and existential emptiness in patients. Studies conducted with women with gynecological cancer have shown that the frequency of women experiencing PTSD varies between 9.25% and 70%, and women experience at least two of the symptoms of PTSD. Cancer patients report that they feel lonely, they can hardly control their anger, they are disappointed, they feel unhappy and meaningless. Studies focusing on the experiences of cancer patients have revealed that nearly half of the patients experience meaninglessness and hopelessness. Therefore, it is the primary responsibility of health professionals/nurses to accompany and contribute to the journey of cancer patients to find meaning. Research Hypotheses 1. The total mean TSSS score of the women in the experimental group who participated in the logotherapy interviews was lower than that of the women in the control group (H1). 2. The total mean PTGI score of the women in the experimental group who participated in the logotherapy interviews was higher than that of the women in the control group (H1). 3. The total mean MLQ score of the women in the experimental group who participated in the logotherapy interviews was higher than that of the women in the control group (H1). 4. The total mean SWBS score of the women in the experimental group who participated in the logotherapy interviews was higher than that of the women in the control group (H1).

Nct (2022). "Effect of Mobile Application on Urinary Incontinence." ClinicalTrails.gov.
	Conservative, surgical, and pharmacological treatment methods are available in the treatment of urinary incontinence. Despite this, the first preferred method of treatment is the conservative treatment method. One of these methods and the most preferred one is pelvic floor muscle training (Kegel exercise). The reason why it is one of the most preferred treatment methods is that it is a reliable and effective method in reducing UI and increasing the quality of life. Research shows that mobile applications are effective in maintaining pelvic floor muscle exercise (Kegel exercise), improving quality of life, reducing urinary incontinence symptoms, accelerating the healing process, and facilitating access to care.

Nct (2022). "The Effect of Music Therapy on Sleep Quality and Depression in Menopausal Women." ClinicalTrails.gov.
	According to WHO, the menopausal period is not a pathological process, but is expressed as one of the biological stages of a woman's life. The menopausal period is defined as the transition to old age, which begins with regression in ovarian functions and decreased reproductive capacity, and in time, reproductive ability ends. Approximately one‐third of women experience no symptoms or mild symptoms during the menopausal period, while the other third experience moderate symptoms, while the remaining one‐third may experience severe symptoms. The symptomatology experienced in this period is characterized by a hypoestrogenic state that occurs due to regression in ovarian function in 60% to 80% of women . In addition to symptoms such as insomnia, vaginal dryness, irregular menstrual bleeding, depressed mood, irritability, headache, forgetfulness, and dizziness, vasomotor symptoms such as changes in body thermoregulation and night sweats can be observed in menopausal women as a result of insufficient secretion of sex hormones. Sleep problems are defined as one of the important problems seen in menopausal women It is stated that hot flashes and especially night sweats seen in the menopausal period may cause sleep disorders with the slowdown in serotonin metabolism due to hypoestrogen. While sleep problems can negatively affect mood and activities of daily living in women, it has been reported that they have a wide‐ranging negative impact on quality of life, mood, productivity and physical health, especially in women with severe sleep problems. It is stated that sleep disorders do not only affect the quality of life in women in the menopausal period, but may cause social burdens by jeopardizing their lives and health in the long run. It is stated that depression affects approximately 350 million people worldwide and is a global burden. It is stated that depression is seen twice as often in women as in men, and that the risk of depression may increase during periods when women experience hormonal changes such as puberty, pregnancy, and transition to menopause.It is stated that the menopausal period, in which hormonal changes are experienced intensively, is not associated with psychiatric diseases alone, but the risk of its occurrence increases, especially in women in the perimenopausal period, even if there is no previous history of depressive disorder. It is stated that hormone therapy, one of the pharmacological methods, is accepted as an effective and standard method in the management of menopausal symptoms, including sleep disorders and depression, despite its side effects. However, due to the health risks associated with hormone therapy, it is stated that many women do not want to use this treatment option and turn to complementary and alternative medicine to alleviate menopausal symptoms. It is stated that physical, mental and psychological problems of women can be treated with non‐pharmacological methods such as relaxation, breathing exercises, touch therapy, and music therapy as a complementary and alternative medicine approach in the world and in Turkey. It is stated that the healing effect of music has been known among societies since ancient times. Today, with technological developments, it is stated that music does not only rest the soul, but also has a cognitively stimulating effect and a motivating effect in cases where verbal communication cannot be performed. The importance of music therapy and its relationship with treatment was emphasized by Florence Nightingale in the early 1800s, and it was used as a therapeutic approach, accepted the power of the use of appropriate music in the healing of patients and defined music therapy as a part of the healing process Lafcı in 2018 found that music therapy had positive effects on sleep and anxiety in women with breast cancer. Kavurmacı in 2019 found that music therapy positively affects sleep quality in their study with students. It is stated that music has a therapeutic effect on mental illnesses such as depression by regulating the stress response of th ypothalamus‐pituitary‐adrenal axis. According to the meta‐analysis results in which music therapy studies applied to patients with digestive tumors were examined, it was determined that the sleep quality could be improved and the level of depression could be reduced in those who received music therapy. It was found that music therapy had a significant effect on sleep quality and depression in patients who applied to the psychiatry outpatient clinic due to insomnia in Iran. Koçak in 2022 found that music therapy positively affects depression in menopausal women. When the national and international literature is examined, there are many studies on non‐pharmacological methods for menopausal symptoms, while the effect of music therapy on depression in menopausal women was examined in only one study in Turkey. However, no study was found in which the music therapy method was used for both depression and sleep quality in menopausal women. Based on this argument, a study was planned to examine the effect of music therapy on sleep quality and depression in menopausal women. Material and Method The research will be carried out with menopausal women who applied to Çayyolu No. 1 FHC between August 2022 and December 2022. The research was designed as a randomized controlled experimental study. The sample of the study was G‐Power 3.1.7; By comparing the sleep quality scores between the groups, it was planned to have 35 cases in the experimental and control groups.Sampling will be done by dividing the menopausal women who apply to the FHC, who meet the inclusion criteria, into the experimental and control groups at a rate of 1/1. Considering the risk of data loss in both groups, 20% more cases will be taken. Since the variables to be examined in our study are depression and sleep quality, the type of music to be used will be zirgüle makam and Hüseyni makam. When the effects of authorities on the human spirit are examined; It is stated that while the zirgüle maqam gives people sleep, the huseyni maqam gives people comfort . A WhatsApp group will be created with the experimental group. The links of the authority that will be played via Whatsapp will be sent.They will be asked to listen to the Hüseyni makam for at least 15 minutes at 11.00 in the morning, 5 times a week for 5 weeks, and to listen to the Zirgüle makam for at least 15 minutes at 20.00 on the same day. Feedback will be received via WhatsApp that the participants have listened to the maqam conveyed to them.Before applying music therapy in the experimental group, they will be asked to fill out the questionnaires.At the end of the music therapy application, the questionnaires made at the beginning will be applied to the experimental group again.No application will be made to the control group, and data collection forms will be applied twice with an interval of 4 weeks. Data Collection Tools 1. Sociodemographic Information Form The first 9 questions question the participant's sociodemographic characteristics such as age, weight, height, occupation, educational status, and the next 10 questions consist of questions prepared to determine the obstetrical characteristics.While the next question was asked to detect the presence of chronic disease in the person, the last two questions were asked to detect the presence of cancer and depression.The sociodemographic information form consists of 21 questions in total. 2. Beck Depression Inventory In the study, Beck Depression Inventory will be used to evaluate the presence and severity of depression symptoms.The inventory was developed by Beck (1961) in order to express the degree of depression objectively through numbers.The Turkish adaptation of the inventory was made by Hisli (1988).For each of the 21 items that make up the inventory, there are four self‐evaluation statements rated from zero to three, ranking the severity of the symptom from least to greatest.The lowest score that can be obtained from the inventory is 0 and the highest score is 63.The high total score indicates the high level of depression or its ev rity.In addition, a cut‐off point of 17 is recommended for catching clinical depression. 3. Menopause Symptoms Rating Scale The scale was developed by the Berlin Center for Epidemiology and Health Research The validity and reliability study in Turkey was conducted by Metintaş in 2009.The 11‐item Likert‐type scale including menopausal complaints consists of 3 sub‐dimensions.Somatic complaints sub‐dimension; Items 1, 2, 3, 11, psychological complaints sub‐dimension; 4th, 5th, 6th, 7th items and urogenital complaints sub‐dimension; It includes items 8, 9, 10. For each item; 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe and the minimum score that can be taken from the scale is 0, and the maximum score is 44.An increase in the total score obtained from the scale indicates that both the severity of the complaints experienced and the quality of life are negatively affected. 4. Pittsburg Sleep Quality Scale (PUKÖ) It was developed by Buysse in 1989, and its validity and reliability study in Turkey was performed by Ağargün in 1996. PUKÖ consists of a total of 24 questions. 19 of the questions are self‐evaluation questions, 5 of them are answered by the spouse or relative.Question 19 is not taken into account in scoring. PUKO; It consists of seven items evaluating subjective sleep quality, sleep delay, sleep duration, sleep efficiency, sleep disturbance, use of sleeping pills, and impairment in daytime work. Each component is evaluated with a score between 0‐3.The scale total score is between 0‐21. A PUKÖ total score of 5 and above indicates poor sleep quality.Its diagnostic sensitivity is 89.6% and its specificity is 86.5%. It takes 5‐10 minutes to complete the scale Evaluation of Data The data will be analyzed in SPSS program. Student's t test will be used for two independent group variables with normal distribution, Mann Whitney U test for data that is not normally distributed, and chi‐square test for categorical variables

Nct (2022). "The Effect of Nursing Care Program on Women With Endometriosis." ClinicalTrails.gov.
	This experimental study, which was conducted in a single‐blind, with control group, prospective, randomized type in the first test‐post‐test order, was carried out in the endometriosis polyclinic of Istanbul Zeynep Kamil Gynecology and Pediatrics Training and Research Hospital. In the preliminary evaluation, 46 women with Endometriosis Health Profile Questionnaire‐5 (EHP‐5) scores of 22 and above (50 and above in the 100 system) constituted the sample of the study, including 23 intervention and 23 control groups. While the Nursing Care Program for Women with Endometriosis (NCPE) was applied to the intervention group, only routine care was applied to the control group. Introductory Information Form, EHP‐5, Healthy Lifestyle Behaviors Scale II (HLBSII), and Satisfaction Questionnaire for NCPE were used as data collection forms in the study.

Nct (2022). "The Effect of Pelvic Floor Muscle Exercises Applied During Pregnancy on Genito-Pelvic Pain Level in Postpartum Period." ClinicalTrails.gov.
	Introduction Some important changes are observed on the pelvic floor musculature during the pregnancy and labour. Stretching occurs in nerve, muscle, fascia and ligament structures in the pelvic floor. This affects the pelvic floor musculature, causing dysfunction and pelvic pain. As a result of the study by Paterson et al. (2009), women stated that genito‐pelvic pain started during pregnancy. Women reported that genito‐pelvic pain was localized only on both sides of the genital area during pregnancy, and the pain was only in the genital area in the first days of the postpartum period. It is estimated that genito‐pelvic pain occurs in approximately 22% of pregnancy [3]. Acute genito‐pelvic postpartum pain is a common problem regardless of vaginal delivery or caesarean section. Acute postpartum genito‐pelvic pain rates can be up to 85%. This rate is observed as 92% one day after caesarean and vaginal delivery. Postpartum pain due to acute injuries from birth usually gets better in the first 2‐3 months. However, for some new mothers, acute genito‐pelvic pain may persist longer after delivery. Considering that there are over 100 million births per year worldwide, the risk of women experiencing genito‐pelvic pain increases accordingly. According to these estimations, at least one million women worldwide may suffer from persistent postpartum genito‐pelvic pain for one year or more after giving birth. Acute genito‐pelvic pain, on the other hand, negatively affects the recovery of the perineal region in the postpartum period, problems in bladder and bowel functions, and activities of daily living. Pelvic floor muscle exercises strengthen the pelvic floor muscles and increase urethral sphincter pressure. Strengthened pelvic floor muscles provide cushioning support to the pelvic organs and prevent pelvic organ prolapse and urinary incontinence by increasing urethral sphincter pressure (and promoting urethral muscle hypertrophy). They are also involved in sexual function and continence. Pelvic floor muscle exercises are exercises that provide the strength, endurance, contraction, relaxation or development of the pelvic floor muscles. In line with this literature, this study was conducted to determine the effect of pelvic floor muscle exercises applied during pregnancy on the level of genito‐pelvic pain after delivery.

Nct (2022). "Effect of Periodized Resistance Training and High Intensity Training on BMI and QOL in PCOS." ClinicalTrails.gov.
	Poly cystic ovarian syndrome (PCOS) is a hormonal disorder which is most common in females with fertile age. A number of small fluid filled sacs formed in ovaries which results in failure of egg release. Poly cystic ovary syndrome (PCOS) is an endocrine problem which is characterized by the polycystic ovaries, menstrual problems, infertility, metabolic disorder, psychological problems, elevated androgens, hirsutism, acne and obesity. PCOS also causes psychological disorders which include depression, anxiety, poor body image, low self‐esteem and decreased health‐ related quality of life. Some well‐controlled randomized clinical studies have been conducted to evaluate the effects of exercise training program in women with PCOS. There are many beneficial effects of exercises which improve physical fitness, body composition, and cardiovascular, hormonal, reproductive and psychological outcomes. Periodization training program involves period of active rest which allows muscle adaptations through variable intensity, volume and rest. The advantage of periodization is that it prevent from overtraining symptoms such as muscle stiffness, muscle soreness, sprain, strain, possible injury and decreased performance. High intensity interval training is effective in reducing body mass index and improving body composition in females with PCOS. The study will be a randomized clinical trial and will be conducted in Mohsin memorial hospital Faisalabad. This study will be completed in time duration of ten months after the approval of synopsis and convenient sampling technique will be used. Total twenty four subjects will be assigned randomly by using lottery method into two groups. Group A will receive periodized resistance training and Group B will receive high intensity interval training. Warm up and cool down period of ten minutes of treadmill training will be performed by both groups. Data will be collected from all participants at baseline and after 8 weeks of treatment by using BMI and WHO‐QOL BREF questionnaire. After assessing the normality data will be analyzed by using parametric or non‐parametric test by using SPSS‐25.

Nct (2022). "The Effect of Pilates Exercise and Whatsapp Text-Based Support Program on Premenstrual Syndrome (PMS) Symptoms." ClinicalTrails.gov.
	In this study, it will be answered whether the Pilates exercise and the support program based on Whatsapp text messages have an effect on the PMS symptoms experienced by university female students. Demographic information of the participants will be collected with the Personal Information form. The personal information form is a form prepared by the researchers with the support of the literature, consisting of 21 questions aiming to obtain information about the socio‐demographic characteristics, menstrual characteristics, and lifestyle behaviors of the students. PMS symptoms will be evaluated with the Premenstrual Syndrome Scale. First of all, the premenstrual syndrome scale will be applied by trying to reach all 380 female students studying at the school. Afterward, 68 students with PMS who meet the inclusion criteria will be divided into 34 intervention and 34 control groups by simple randomization. In order to prevent interaction between the intervention and control group students in the randomization, the places where the students stay (home, dormitory rooms) will be taken into account. A support program including pilates exercise and WhatsApp text messages will be applied to the initiative group for 8 weeks. No attempt will be made on the control group.

Nct (2022). "Effect of Preoperative Tamsulosin on Postoperative Urinary Retention." ClinicalTrails.gov.
	Postoperative urinary retention has been defined as the inability to void despite having fluid in the bladder during the postoperative period. Urinary retention after pelvic reconstructive surgery requiring indwelling catheter or self‐catheterization usage occurs in approximately 30‐60% of patients postoperatively. During a retro‐fill voiding trial, the bladder is back‐filled with a set amount of sterile water (often 300mL), the catheter is removed, the patient is permitted to void and the voided volume is compared with a bladder scan post void residual volume. "Passing" a voiding trial has previously been defined as voiding equal or greater than ⅔ the residual volume, whereas others characterize "passing" as voiding at least 200mL and voiding a greater volume than the post‐void residual volume. If the patient does not "pass" the voiding trial, the patient is characterized as having postoperative urinary retention and is discharged home with an indwelling catheter to prevent detrusor injury from bladder over‐distention, pain and urinary tract infection. Many women consider being discharged home with a foley catheter to be a surgical complication and describe catheter use as the worst aspect of their surgery. Indwelling catheters are the leading cause of hospital‐acquired urinary tract infections (UTIs), are often a source of embarrassment and inconvenience for patients, and often require additional office visits and healthcare utilization. Tamsulosin is an alpha‐adrenergic receptor blocker which is thought to increase smooth muscle relaxation and improve urinary flow. Current literature has been primarily focused on the effect of tamsulosin in men with benign prostatic hyperplasia, however may be beneficial in women as well with limited studies for postoperative urinary retention. Chapman, et al published a randomized control trial evaluating postoperative urinary retention after female pelvic reconstructive surgery. These patients underwent 10 days of tamsulosin (3 days preoperative and 7 days postoperative) and were found to have a 65% decrease in the urinary retention rate from 25.8% to 8.8%. Livne, et al published a study evaluating postoperative urinary retention decrease of 79.2% after postoperative administration of dibenzyline (an alpha‐adrenergic receptor blocker) in women undergoing hysterectomy (post‐operative urinary retention rate of 18.75% in controls and 3.9% in the treatment group). Additional studies have also been published evaluating postoperative urinary retention in men and women undergoing various surgeries and have demonstrated a decrease in postoperative urinary retention after tamsulosin administration from 72‐88% compared with controls. These studies vary in tamsulosin administration from multiple days preoperative and postoperative to multiple doses preoperative and postoperative to a single postoperative dose, however no studies have been published in evaluating a single preoperative dose of tamsulosin and the effect on postoperative urinary retention. This has previously been studied as tamsulosin reaches a steady state in approximately 5 days, however when tamsulosin is given in a fasting patient, it can reach the maximum blood concentration in approximately 4‐5 hours. As the majority of female pelvic reconstructive surgeries performed by our department are same‐day surgeries, with patients being discharged the day of surgery, the investigators would like to investigate the effect of a single preoperative dose of tamsulosin on postoperative urinary retention and, by effect, home catheter usage after surgery. Tamsulosin is cost‐effective at approximately $2 per tablet. Despite primarily being prescribed for benign prostatic hyperplasia, tamsulosin has been found to be a safe and well‐tolerated treatment for voiding dysfunction in women. Postoperative urinary retention is common after pelvic reconstructive surgery with mid‐urethral sling placement and is extremely bothersome to patients. Tamsulosin is a low‐risk, well tolerated, cost‐effective medic ion that studies have suggested may decrease the rate of postoperative urinary retention. No study to date has evaluated preoperative administration of single‐ dose tamsulosin for postoperative urinary retention in a randomized placebo‐controlled trial.

Nct (2022). "The Effect of Progressive Muscle Relaxation Exercises." ClinicalTrails.gov.
	With preterm birth, some medical and neurophysiological problems occur in the baby. The mother‐father‐infant interactions of these babies, who need more intensive care support after birth, are negatively affected by this process. The mother whose baby is in intensive care is separated from her baby and is worried for her life because her baby is underdeveloped and has frequent health problems. All these experiences may cause the mother to lose her maternal role. Therefore, mothers; They may experience a range of negative emotions such as sadness, mourning, fear, grief, disappointment, anger and helplessness, as well as significant psychological disturbances such as postpartum depression and anxiety disorders. Therefore, appropriate interventions are necessary for early diagnosis and reduction of depression in the postpartum period. Stress‐reducing practices such as PMR to be applied to the mother can reduce the mother's anxiety and depression levels, as well as increase breastfeeding self‐efficacy. Decrease in depression and increase in breastfeeding self‐efficacy will positively affect the mother's breastfeeding and contribute to the growth of the baby. Participants and sample: The universe of the study consisted of mothers with preterm infants of 32‐36 weeks of gestation who were hospitalized in the NICU. Sample selection criteria were determined as follows mother's having between 32‐36 weeks preterm babies, mother's having enough milk to breastfeed, baby's not having an anomaly that prevents breastfeeding, baby's being fed with breast milk. To determine the sample size of the study, the power analysis was performed based on a previous study. According to the G*Power analysis result (with a test power of 95% confidence and power of 95.82% for ß: 0.04, alpha: 0.05), the sample size was found to be 70. Considering the possibility of case loss, the total sample size was determined 80 (40 in the experimental group and 40 in the control). The final number of mothers in the experimental group was 35 and 35 in the control group. As a result, 70 mothers in total were included in the analysis. Data collecting: Intervention: When premature babies were admitted to the NICU, all parents were informed about intensive care settings and premature birth. PMR exercises were applied to the mothers in the experimental group by the researcher and the mothers were given training on the application of the exercises. Procedure: Interventions in the experimental group: Introductory information form and EPDS were completed by the mothers before the PMR exercises. PMR exercises were applied to the mothers by the researcher in the milking room (a quiet room) located on the NICU floor and they were given training on the application of the exercises. During the application, it was ensured that only the researcher and the mother were in the room. The application was continued until the mother was able to do the PMR exercises on her own. In case the mother applied the PMR exercises incompletely or incorrectly, the researcher did it to ensure that the mother performed the exercises correctly. It took about 30‐45 minutes to do the exercises. After the application and training, the mother was given a guide on the steps of the PMR exercises. The mother was asked to perform the exercises twice a day, in the morning and evening, and record them on the follow‐up form. The researcher's contact number was given to the mother for counseling in case she had difficulty following the steps of the PMR exercises. During the follow‐ups, the mother was called by the researcher and a message was sent to ensure her continuity in the exercises. At the end of the 1st and 2nd weeks of the follow‐up, BSES, EPDS and patient follow‐up forms were filled when the mother came for routine controls. Interventions in the control group: The descriptive information form, BSES and EPDS were first administered to the mothers. BSES and EPDS were applied to the mothers at the end of the 1st and 2nd weeks of follow‐up. At the end of the 2nd week, mother ere told how to perform PMR exercises and instructions on PMR exercises were given. Measurements: Information Form: In this form, there are 8 questions about the sociodemographic characteristics of the mother, her working status during pregnancy, the mode of delivery, her participation in the care of the baby in the hospital, the breastfeeding status of the previous baby and the support status of the mother, and the care of the baby after discharge. Edinburgh Postpartum Depression Scale (EDPS): It was defined by Cox et al. in 1987 and has been accepted all over the world as a tool that can be used in the recognition of postpartum depression by proving its validity and reliability in many countries, in different languages, until today. It is reported that it can be used for (one) routine screening in all women who have given birth. Validity studies were conducted in 2 separate studies in Turkey, and it is reported that when the cut‐off score is 12‐13, it is more sensitive in detecting people with true depressive symptoms. The Edinburgh Postpartum Depression Scale is not a diagnostic scale, it is used for symptom screening. The diagnosis needs to be confirmed by clinical examination. The Edinburgh Postpartum Depression Scale is a scale consisting of 10 questions, each of which asks the mother to report how she has felt over the past week by ticking one of four different options. The total score is calculated by giving a score between 0‐3 for each item. In some items, the harshest responses are placed at the beginning, while in others they are placed at the end. The score varies between 0‐30. Postpartum Breastfeeding Self‐Efficacy Scale (BSES): It is a 33‐item scale developed by Dennis and Faux in 1999 to evaluate mothers' breastfeeding self‐efficacy levels. Later, in 2003, a 14‐item short form of the scale was developed. The Breastfeeding Self‐Efficacy Short Form is a 5‐point Likert‐type scale (1 = "I'm not sure at all" and 5 = "I'm always sure"). The lowest score that can be obtained from the scale is 14, and the highest score is 70. The higher the score, the higher the breastfeeding self‐efficacy. The Turkish validity and reliability study of the scale was carried out by Alus Tokat and Okumuş in 2009. Patient Follow‐up Form: It was created to track whether mothers of premature infants performing PMR did this exercise twice a day, morning and evening, for a month. Practice and Guidelines for Progressive Muscle Relaxation (PMR) Exercises: Before collecting data, one of the researchers received training and certification from a psychotherapist who is an expert in this field in order to be able to perform the PMR exercises. Guidelines for PMR exercises have been prepared in line with the literature and the training received by the researcher. In the guidelines, the person is asked to be in a comfortable place and position, to reach the face by following the large muscle groups gradually, starting from the feet, to tense the muscles in each step, and then to release them. It is necessary to take a deep breath after each muscle group, to stop for a while, and release it slowly.

Nct (2022). "The Effect of Progressive Relaxation Exercises on Premenstrual Syndrome Symptoms." ClinicalTrails.gov.
	Institutional permission and ethics committee approval were obtained for the research. The population of the study consisted of 218 women. The sample of the study consisted of 80 women, 40 of which were experimental and 40 control. Participants were evaluated according to the www.randomizer.org program and randomization was achieved among the women participating in the study. The research process and the participants in the experimental and control groups will be explained again and the necessary equipment will be provided by the researchers. The "Progressive Relaxation Exercises Guide" prepared by the researcher in accordance with the literature will be given to the women in the experimental group (40), taking the opinions and suggestions of eight experts. At the same time, the comprehensibility and applicability of the guide were evaluated by making a pilot application to 10 women before the research. Afterwards, all the information in the guide will be explained to the women in the experimental group and training will be given until adequate feedback is received. At the same time, progressive relaxation exercises belonging to the Turkish Psychological Association were given to the women in CD form, and listening to the audio recordings together with the relaxation exercises to be performed in accordance with the guide will be indicated. These exercises will be performed by the women in the experimental group for 25‐30 minutes a day, every day for 8 weeks. At the end of 8 weeks, women will be reassessed with PMSS. The women in the control group (40) will be told to continue their routine habits regarding PMS in parallel with the study group, without any application. At the end of 8 weeks, women in the control group will be re‐evaluated with PMSS.

Nct (2022). "The Effect of Psychoeducation on Dysmenorrhea in Nursing Students." ClinicalTrails.gov.
	This study will be conducted to examine the effect of psychoeducation based on Leventhal's Self‐Regulation Model on dysmenorrhea in nursing students. Hypotheses of the Research H0a: There is no difference in menstrual pain severity between the experimental group and the control group receiving psychoeducation based on Leventhal's Self‐Regulation Model. H0b: There is no difference between the Functional and Emotional Dysmenorrhea Scale mean scores between the experimental group and the control group receiving psychoeducation based on Leventhal's Self‐Regulation Model. H0c: There is no difference between the Menstruation Symptom Scale mean scores between the experimental group receiving psychoeducation based on Leventhal's Self‐Regulation Model and the control group. Menstrual pain severity in women in the experimental and control groups is the primary result of the study. Functional and Emotional Dysmenorrhea Scale and Menstruation Symptom Scale mean scores of the women in the experimental and control groups constitute the secondary results of the study. Type of research The research is a single‐center parallel group single‐blind randomized controlled experimental study. The study will be conducted in accordance with the CONSORT checklist. Participants and setting The population of the research will be female students studying at the Nursing Department of Bitlis Eren University. In order to determine the sample size of the study, a power analysis (G*Power 3.1.9.4 version) was conducted by taking the study results of Yılmaz and Şahin (2020), which is similar to our study, as reference. According to the power analysis, the sample size was determined as 62 women in total (d=0.75; α= 0.05; 1‐β=90%). However, by calculating the drop out rate ( 5%) in the study of Yılmaz and Şahin (2020), 33 women will be included in each group in our study. Validity‐Reliability of the Research Selection bias Inclusion criteria were determined to avoid selection bias. All women who met the following criteria were invited to participate in the study. Inclusion criteria, ‐ Having a regular menstrual cycle of 6 months ‐ Being Nulliparous ‐ Getting 4 or more points from VAS ‐ Having smart phone and internet facility ‐ Having the technical means to use the ZOOM application ‐ Volunteering to participate in the research Exclusion criteria, ‐ Having a diagnosis of any gynecological disease ‐ Having a history of gynecological surgery ‐ Having an active vaginal infection ‐ Not having received psychosocial counseling for dysmenorrhea before Distribution bias (randomization): Simple randomization method will be used in the randomization of the research sample. Participants who are determined to meet the research criteria will be assigned to the experimental and control groups according to the assignment list created through the computer program. Implementation bias: In this study on implementation bias, participant blinding will be done. For this purpose, an active control group will be used in the research. However, since the implementation of the research will be done by the researchers, the researcher cannot be blinded. Detection bias (detection bias; How the results were collected): Measures to prevent detection bias will be made using an online questionnaire. Reporting bias (blinding the person who wrote the report and analyzed the data): The data obtained from the research aimed at preventing reporting bias will be coded as A and B by an independent statistician and transferred to the SPSS program. Analysis of the data will also be done by an independent statistician. Attrition bias (reduction bias): In case of a decrease in the sample, ITT analysis will be performed. Data Collection Inclusion Criteria Form, Descriptive Information Form, Visual Analog Scale, Functional and Emotional Dysmenorrhea (Painful Menstruation) Scale and Menstruation Symptom Scale will be used to collect data. Introductory Information Form; The Introductory Information Form is a 14‐question form prepared by the researchers to e ermine the sociodemographic characteristics (age, income level, family type, longest living place) and characteristics of menstruation and dysmenorrhea (age of menarche, duration of pain, need for analgesic use, analgesics used, applications for pain relief) of the participants. Visual Analog Scale (VAS); VAS is a one‐dimensional scale that is widely used today to measure subjective parameters such as pain intensity. The VAS is a 10 cm long ruler drawn horizontally or vertically, starting with "No pain" and ending with "Unbearable pain". The patient is instructed to place a mark on this line, which corresponds to the severity of the pain, to cross this line. The numerical index of the patient's pain intensity in cm or mm is obtained by measuring the distance from the lowest VAS level to the patient's mark with a ruler. In the VAS, the severity of pain is graded between 0 and 10 points. Usually, "no pain" is rated as 0 points and "worst pain imaginable" is 10 points. Ranges for pain intensity; <3 mild pain, 3‐6 moderate pain, >6 severe pain. Functional and Emotional Dysmenorrhea (Painful Menstruation) Scale; The Functional and Emotional Dysmenorrhea Scale (FEDS) is a Likert‐type scale used to evaluate dysmenorrhea functionally and emotionally. Li et al. (2012) Turkish validity and reliability study of the scale was carried out by Gün (2014). The Cronbach's Alpha coefficient of FEDS, which consists of 14 items and two sub‐dimensions, is 0.91. Each item is scored between 1 (one) and 5 (five). There is no reverse item in the scale. As the scores obtained from the scale increase, the level of functional and emotional impact of dysmenorrhea also increases. Menstruation Symptom Scale (MSS); It is a scale developed by Chesney and Tasto in 1975 to evaluate menstrual pain and symptoms. In 2009, Negriff et al. factor structure and usability on adolescents were re‐evaluated and updated. Guvenc et al. Turkish validity and reliability were made in 2014 by Güvenç, Seven, & Akyüz, 2014. MSS is a five‐point Likert‐type scale consisting of twenty‐two items. Participants are asked to give a number between 1 (never) and 5 (always) for the symptoms they experience about menstruation. The scale has three sub‐dimensions: 'Negative Effects/Somatic Complaints' (Items 1‐13), 'Menstrual Pain Symptoms' (Items 14‐19) and 'Coping Methods' (Items 20‐22). The highest score that can be obtained from the scale is 110, and the lowest score is 22. The MSS score is calculated by taking the total mean score of the items in the scale. An increase in the mean score indicates an increase in the severity of menstrual symptoms. The score obtained from the sub‐dimensions is calculated by taking the total score average of the items in the sub‐dimensions. The increase in the mean score for the sub‐dimensions indicates that the severity of menstrual symptoms related to that sub‐dimension increases. The Cronbach's Alpha value of the original scale is 0.86. Application of Research There will be two groups in the research, namely the experimental and control group. The eligibility of the participants to be included in the study will be determined by using the inclusion criteria form. Introductory Information Form, VAS, Functional and Emotional Dysmenorrhea Scale and Menstruation Symptom Scale will be applied to the participants who are determined to be eligible for inclusion in the study. After filling out the forms, assignments to the groups will be made by randomization. Experimental group‐Intervention group Based on Leventhal's Self‐Regulation Model Students assigned to the experimental group will be divided into groups of 6‐9. 3 psychoeducation sessions will be held with each group once a week for a total of 3 weeks. Group sessions are estimated to last between 60‐75 minutes. Psychoeducational content based on Leventhal's Self‐Regulation Model was prepared. In the first stage, cognitive bases of dysmenorrhea, in the second stage, strategies to cope with dysmenorrhea, and in the third stage, the effectiveness of coping tr tegies in dysmenorrhea will be discussed. In the second stage, the participants will be taught the progressive muscle relaxation exercise, which is among the strategies to cope with dysmenorrhea. Sessions will be held online. After the completion of the psychoeducation session, measurements will be made in 3 consecutive menstrual cycles, starting from the first menstrual cycle. Measurements will be made on the first day of each menstrual cycle using the VAS, the Functional and Emotional Dysmenorrhea Scale, and the Menstruation Symptom Scale. Control Group The control group will be given a online training of 30‐45 minutes covering dysmenorrhea and coping in a single session. From the first menstrual cycle after the training session is completed, measurements will be made in 3 consecutive menstrual cycles. Measurements will be made on the first day of each menstrual cycle using the VAS, the Functional and Emotional Dysmenorrhea Scale, and the Menstruation Symptom Scale.

Nct (2022). "Effect of Reiki Application on Menopausal Symptoms." ClinicalTrails.gov.
	Parallel to the increase in life expectancy by years, the population of women living in the post‐menopausal period is also increasing. In order to have a healthy menopause, which is an important part of women's life, it is thought that the distant reiki without health risks by women may be effective in reducing the symptoms of menopause experienced by women. In line with this information, it was aimed to determine the effect of distant reiki on menopausal symptoms. The study was carried out with menopausal women between the ages of 40‐55 in Adana province in Turkey. Therefore, in the study, 48 women in the menopausal period between the ages of 40‐55 was randomly assigned to reiki and control groups. Distant reiki application for 30 minutes three times a week for four weeks was applied individually to the study group. No intervention was made to the control group for a period of four weeks. The primary expected outcome of the research is the effect of distant reiki on menopausal symptoms of menopausal women. Results was applied three times in total, before the study and control application, 4 weeks and 8 weeks later.

Nct (2022). "Effect of Sterile Versus Clean Gloves Intrapartum and Postpartum Infections at Term." ClinicalTrails.gov.
	Introduction The vaginal microbiota consists of a wide array of possible bacteria including species Ureaplasma, Listeria, Lactobacillus, Atopbium, Megasphaera, Leptotrichia, Peptostreptococcus, Prevotella, Diphtheria, Escherichia, Klebsiella, Enterobacter, Proteus, Pseudomonas, Gardnerella, Staphylococcus, and Streptococcus.1,2 However, the uterus is thought to be much less diverse in flora and possibly sterile, especially in the setting of pregnancy.3 Thickening of the cervical mucus functions as a buffer to prevent the polymicrobial vaginal bacteria from ascending into the uterus in pregnancy. Intraamniotic or intrauterine infections (IAI), also known as chorioamnionitis, are thought to occur most frequently from an ascending infection from the lower genital tract into the uterine cavity.4 IAI usually warrants immediate delivery and impacts 5 ‐ 12% of term pregnancies, with the most commonly identified pathogenic species being Ureaplasma.5‐7 IAI carries significant neonatal morbidity including increased risk for neonatal pneumonia, bronchopulmonary dysplasia, poor neonatal growth, dermatitis, necrotizing enterocolitis, retinopathy of prematurity, cerebral palsy, meningitis, sepsis, and death.4,7 When performing cervical examinations during labor, providers in the United States commonly use a sterile glove to examine dilation and effacement of the cervix and station of the fetal head, although there are no data currently to support that this practice reduces rates of infection. Even though the uterus could be sterile in normal pregnancies, the provider performing the cervical examination must traverse the milieu of diverse vaginal bacteria in order to reach the cervix to perform the exam, introducing vaginal microbiota into the uterus. Despite this, it is unclear if the number of cervical examinations impacts risk of infection, especially before rupture of membranes (ROM).8,9 Common risk factors for IAI acknowledged by the American College of Obstetrics and Gynecology (ACOG) include excessive number of cervical examinations (especially after rupture of membranes), cervical insufficiency, internal fetal heart rate or uterine contraction monitors, intracervical balloon catheters for induction of labor, urogenital pathogens (sexually transmitted infections (STI), group B streptococcus (GBS) colonization, bacterial vaginosis), nulliparity, alcohol and tobacco use in pregnancy, and meconium‐stained amniotic fluid.4 Nevertheless, some of these factors are also associated with longer duration of labor, rupture of membranes, and more cervical examinations, so they may not be independently associated with IAI.8,10 The theory behind IAI, assuming there are no other sources of maternal infection present elsewhere that could be introduced into the uterus or passed through the placenta, is that an infection ascends from the vagina into the intrauterine or intraamniotic space to cause the infection. We hypothesize that the type of glove used for examination should not impact rates of intrapartum or postpartum infection since the glove, whether originally sterile or not, would have to pass through the unsterile vagina to reach the cervix to perform the cervical examination. This prospective randomized controlled study examines whether the type of glove used (sterile vs clean) impacts the rates of IAI in patients receiving cervical examinations during labor or induction of labor at term. Methods Patients meeting the inclusion and exclusion criteria below provided written informed consent to participate in the study after admission to labor and delivery at the single institution tertiary care referral center for this study. Any cervical examinations performed prior to the patient being consented to participate in the study were not included, such as if performed in the office or in the triage area, prior to admission. This study followed the format of a randomized prospective cohort study where eligible and consented participants were randomized to receive all cervical examinations with sterile powder‐free polyvinyl chlor e exam gloves (current routine practice, control group) or clean powder‐free nitrile exam gloves (nonsterile, experimental group). Neither the clinical providers performing the exam nor the participants were blinded to the glove type used, however, the researchers did not know which glove type was used while completing the retrospective data collection and analysis. All other obstetrical care provided to the participants was per ACOG guidelines and the only changes made to their care was the type of glove used for this study. Interested participants were eligible to participate if their pregnancy was at term (37w0d to 41w6d gestational age), if their amniotic membranes were intact on admission, if they were presenting in spontaneous labor or were to undergo induction of labor, and if they were attempting for a vaginal delivery initially, even if the final delivery method was by cesarean section. Participants were excluded if they were preterm (before 37w0d gestational age), postdates (after 41w6d gestational age), with ruptured membranes or premature rupture of membranes on admission, in preterm labor, with the diagnosis of chorioamnionitis or any intrauterine infection, with extrauterine infection that would compromise the diagnosis of intrauterine infection (e.g., COVID, upper respiratory infections, urinary tract infections, cellulitis, appendicitis, etc.), experiencing an immunocompromised state (e.g., human immunodeficiency virus, congenital syndromes, transplant recipient, or immunosuppressant use), with uncertainty of their gestational age or no prenatal care, with an intrauterine fetal demise, or requesting a termination of the pregnancy. Twin or multigestational pregnancies were not excluded, however, only singleton pregnancies consented to participate in the study. The primary outcome of the study was the proportion of participants in each glove group who experienced intraamniotic or intrauterine infection or chorioamnionitis or intrapartum infection, these terms are used interchangeably for the purposes of this study. The diagnostic criteria for intraamniotic/intrauterine infection followed the ACOG committee opinion 7124 on the topic, listed below for reference: Patients must have fever >39.0*C (102.2F) ONE TIME without need to recheck temperature in the presence of no other identifiable source of fever OR Fever of 38.0 ‐ 38.9*C (100.4 ‐ 102.02F) on two or more measurements that are at least 30 minutes apart without another clear source PLUS one or more of the following: ‐ Baseline fetal heart rate >160 beats/min for ≥10 minutes, excluding accelerations, decelerations, and periods of marked variability. ‐ Maternal white cell (WBC) count >15,000/mm^3 in the absence of corticosteroids and ideally showing a left shift (bandemia). ‐ Purulent‐appearing fluid coming from the cervical os visualized by speculum examination. The study's secondary outcomes and other data recorded included: Rates of endometritis, maternal age, gravida, parity, induction of labor (IOL) method (foley balloon, cook catheter or cervical ripening balloon, Cytotec (misoprostol), Pitocin (oxytocin), Dilapan, Cervidil), artificial or spontaneous rupture of membrane time (AROM and SROM respectively), time of first cervical exam, number of documented cervical exams, delivery time, delivery method (cesarean section vs vaginal delivery), operative delivery (forceps or vacuum), postpartum hemorrhage (qualitative blood loss > 1000 mL), GBS colonization, gestational diabetes mellitus (GDM), Type 1 or Type 2 diabetes mellitus (T1DM or T2DM, respectively), genitourinary infections (urinary tract infections (UTI), pyelonephritis, gonorrhea (Gc), chlamydia (Ch), trichomonas (Tr), or pelvic inflammatory disease), tobacco/alcohol/drug use in pregnancy, meconium stained fluid, intrauterine pressure catheter (IUPC) use, fetal scalp electrode (FSE) use, epidural use, length of IOL (first cervical exam to delivery time), starting dilation, initial white blood cell (WBC) level on presentation, initial maternal temperature, highest maternal tempe ture, initial maternal heart rate (HR), highest maternal HR, and fetal tachycardia, if present and noted in the maternal chart. Participants were considered GBS colonized if they had a positive rectovaginal culture by polymerase chain reaction (PCR) during routine prenatal care. All patients with a GBS positive status received antibiotics per ACOG recommendations. GBS negative or participants that did not have a GBS rectovaginal culture were not considered GBS colonized in this study to help distinguish those participants receiving antibiotics in labor. Statistical analysis and sample size: Given that the estimated rates of IAI in term pregnancy is estimated to be between 5‐12%, weekly analysis was performed to ensure that interim rates of infection did not exceed 20%, which is double the median expected rate at term and would warrant discontinuation of the study. Data was collected in a deidentified manner from chart review and input into a REDCap database for analysis. The study was approved by the Eastern Virginia Medical School Institutional Review Board under IRB 21‐09‐FB‐0206. Descriptive statistics were used to describe the demographic and baseline characteristics of each cohort. Independent group comparisons were used to assure that the randomization resulted in equal groups at baseline. Continuous variables were compared with a two‐sample independent group t test for normally distributed data or by Wilcoxon‐Mann‐Whitney test for non‐normally distributed continuous variables. For categorical variables, the two groups were compared by Chi square test or Fisher exact test based on expected cell size.

Nct (2022). "The Effect of the Motivational Interviewing Technique on Breast and Cervical Cancer Screenings." ClinicalTrails.gov.
	This study will be conducted to evaluate the effect of the motivational interviewing technique applied to menopausal women on their participation in breast and cervical cancer screenings. This is a randomized controlled intervention study in which the study sample will consist of 120 menopausal women, who visit the health care centers in the city of Kutahya. There will be one intervention group with a total of 60 participants and a control group with the same number of participants. The intervention group will have motivational interviews whereas the control group participants will follow the normal protocols. The Turkish version of Champion's Health Belief Model Scale and The Health Belief Model Scale for Cervical Cancer and the Pap Smear Test will be applied to all the participants in both groups. Then for the intervention group, the motivational interviewing will be carried out in 3 different sessions, each to be conducted one week apart. 6 weeks after the last interview, first follow up would be conducted through phone communication and 6 weeks after the first follow up, a face‐to‐face interview would be conducted for the scales to be applied to the participants again. For the control group, the scales will be applied for the second time at the same time as the intervention group and they will be given a training manual and their questions will be answered by the researchers.

Nct (2022). "Effect of Tibial Transcutaneous Electrostimulation in Women With Urgency Urinary Incontinence." ClinicalTrails.gov.
	A randomized clinical trial, sham‐controlled, comparing behavioral therapy and TTNS (intervention) to the use of behavioral therapy alone. It will include women with 18 years or more, diagnosed with UUI or mixed IU attested by the Questionnaire Overactive Bladder Validated 8 (OAB‐V8). Women with active urinary tract infection in the last four weeks, alcoholics, smokers or drug addicts, with lesions and alteration of skin sensitivity in the place where electrotherapy will be applied, in drug and/or physiotherapeutic treatment for UUI or current OAB, using sleep‐inducing medication, with any neurological disease, using anticholinergic drugs, calcium antagonists, antagonists and dopamine antagonists, with presence of pelvic organ prolapse, during pregnancy or puerperal or with any difficulty in understanding or cognitive deficit that makes it impossible to carry out the research will be excluded. Study variables are behavioral therapy, bilateral transcutaneous tibial nerve stimulation, type of UI, PAL, excessive daytime sleepiness, generic and specific LQ, SQ, UI severity, anxiety level, urinary frequency, nocturia and bladder capacity. Sample size was calculated, adopting a two‐tailed test with the following parameters: α = 0.05, β = 0.20 and statistical power of 80% and 102 women will be included. The study will be carried out in two physiotherapy clinics in Recife, from September 2022 to June 2023, both groups will undergo a behavioral therapy protocol, (bladder training, pelvic floor muscle training and modification of liquid intake). Patients will be submitted to biphasic current and surface electrodes during 12 treatment sessions, twice a week, on non‐consecutive days, with a electrical stimulation device (Quark, Brazil). The following parameters will be used for TTNS: frequency 10Hz (dez Hertz), pulse duration 200 μs (microseconds), for 30 minutes. In the experimental group, the electrodes will be positioned on the medial malleolus of both legs), in order to stimulate the tibial nerve path. In the Sham group, the electrodes will be placed on both legs, centered in the middle of the thigh, where there is no stimulus for the tibial or sacral nerve, for 30 minutes. The project was approved by the Research Ethics Committee of Professor Fernando Figueira Institute of Integral Medicine.

Nct (2022). "The Effect of Trauma Informed Care in Childbirth." ClinicalTrails.gov.
	This is a randomized control experimental study. Data were collected from 100 women who attended supportive care based on trauma informed care or standart care from Turkey between July 2022 and September 2022. Participants who met the inclusion criteria were informed about the purpose of the study and the procedures to be performed, informed consent was obtained from those who agreed to participate, and women were assigned to the groups in line with a computer‐based randomization program with an allocation ratio of 1:1. Block randomization could not be performed because of the different and long delivery processes. Data were collected in both groups at birth (latent phase, active phase, and transitional phase), within 24 hours of birth, and 6th‐8th postpartum days after hospital admission and at least one hour of care. collected by the first author. The CONSORT directive was followed in the planning, implementation and writing of the research.

Nct (2022). "The Effect of Virtual Reality and Distraction Cards on Pain." ClinicalTrails.gov.
	Cervical cancer is the fourth most common cancer worldwide. Cervical cancer is one of the most successfully treatable types of cancer, as long as it is detected early and managed effectively. WHO recommends the use of PAP‐SMEAR and HPV DNA primary screening test to prevent cervical cancer in women. . The crude incidence of cervical cancer per 100,000 women in Turkey in 2020 is . WHO has targeted a threshold of 4 per 100,000 women by 2030 for countries to eliminate cervical cancer. To achieve this goal, 90% of girls should be vaccinated with HPV until the age of 15, and 70% of women should be screened with high performance PAP‐SMEAR and HPV DNA at the age of 35 and 45 For this reason, it is seen that the PAP‐SMEAR test has an important place in the protection of women's health. For the Pap‐Smear test procedure, gynecological examination and speculum examination are included . Experiencing pain, anxiety, shyness and fear during gynecological examination are among the barriers to applying for and taking the pap‐smear test, which has an important place in protecting women's health In the literature, it is seen that virtual reality glasses and distraction cards, which are cognitive behavioral techniques, are used during medical procedures and have a reducing effect on the perception of pain and reduce the level of anxiety . No study has been found that examines the effect on satisfaction and satisfaction levels. However, in line with the results of the study, it is thought that the PAP‐SMEAR procedure will have a positive effect on women's perceived pain and anxiety, and increase their satisfaction levels. It emphasizes the need for cost‐effective and feasible non‐pharmacological methods by healthcare professionals during PAP‐SMEAR application.

Nct (2022). "The Effect of Web Based Education on the Level of Coping With Infertility Stress and Infertility Self-Efficacy." ClinicalTrails.gov.
	Infertility is defined as the inability to conceive or to continue the pregnancy, despite having unprotected sexual intercourse at least twice a week for a year and at least twice a week. It is reported that more than 80 million people around the world are unable to have children due to medical reasons, and 15% of couples in Turkey are diagnosed with infertility. When we look at the literature, it is suggested that infertility and assisted reproduction treatments cause an increase in the level of stress, depression and anxiety in individuals and that it is necessary to strengthen their coping with this process. Aim: This study was planned as a randomized controlled experimental study in order to examine the effect of web‐based education about the treatment process on the level of coping with infertility stress and infertility self‐efficacy to women undergoing Intrauterine Insemination (IUI) treatment. Objective: In the study, it is aimed to reduce the infertility stress level of women undergoing infertility treatment, to increase the level of coping with infertility stress, to increase infertility self‐efficacy, to evaluate the usability of web‐based education in the field of infertility, to increase the effectiveness and quality of education by integrating web‐based education into the nursing care process, and continuous traceability, to prevention of possible wrong treatment process management in the field of infertility, to prevention of possible loss of cycles and to prevention the material and moral couple from being adversely affected by this process. Method: The study was planned to be carried out between 20.01.2022 and 01.06.2023 with women between the ages of 23‐39 who applied to Düzce University Health Practice and Research Center, Infertility Polyclinic. In the research, the Solomon four‐group design sample design consisting of two experimental and two control groups will be used. Power analysis (G*Power 3.1.9.2) was performed on the basis of a previous similar research in the selection of the sample. Accordingly, the sample of the study was planned to consist of a total of 132 patients, 33 patients in each group, taking into account possible data losses. By design, all of the pre‐test and post‐test measurement tools will be applied to the first experimental and control group, and only the post‐test measurement tools will be applied to the second experimental and control group. Randomization will be applied in determining the experimental and control groups. The data will be collected using Personal Information Form (Appendix‐1), Infertility Stress Scale (ISS) (Appendix 2), Coping with the Infertility Stress Scale (CISS) (Appendix‐3), and Infertility Self‐Efficacy Scale ‐ Short Form (ISE‐SF) (Appendix 4). The preliminary application of the research will be completed with an average of 16 women, who constitute at least 10% of the sample of 132 people. Research data will be collected in approximately day 24 to 27 days for each patient from the initiation of Controlled Ovarian Stimulation (COS) treatment to pregnancy determination of patients planned for intrauterine insemination (IUI) treatment. In the research, the experimental group will be given a brief face‐to‐face briefing about the treatment process as well as a detailed training via the website. Web‐based training is 60 minutes in total, including 4 modules. The web‐based training content includes general information about fertility, infertility diagnosis‐treatment methods, drugs used in IUI treatment and its application, and issues to be considered after IUI. The patients in the control group, on the other hand, will be given the hospital's drug administration brochure after brief face‐to‐face information and no other intervention will be made. When the patients come back to the hospital for IUI treatment, they will fill out the Infertility Stress Scale (ISS), Coping with the Infertility Stress Scale (CISS), Infertility Self‐Efficacy Scale ‐ Short Form (ISE‐SF). BHCG results of the patients will b earned on the 14th day after IUI.

Nct (2022). "Effect of Whole Body Vibration on Insulin Resistance in Females With Polycystic Ovarian Syndrome." ClinicalTrails.gov.
	polycystic ovarian syndrome is a complex endocrine condition characterized by metabolic abnormalities such as insulin resistance, excess weight or obesity, diabetes, and an increased risk of cardiovascular disease.Despite previous studies reported that physical exercise improves insulin resistance in females with polycystic ovarian syndrome, there is no study yet investigate the effect of whole body vibration on insulin resistance

Nct (2022). "The Effect of Yoga and Progressive Muscle Relaxation Exercise Practices on Premenstrual Syndrome." ClinicalTrails.gov.
	Menstrual cycle is defined as hormonal and physical changes that continue from menarche to menopause, affecting the whole organism, especially the reproductive organs. During this period, which is necessary for the normal continuation of female reproductive functions and occurs periodically every month, women encounter many menstrual problems. Premenstrual syndrome (PMS), one of the most common problems, is defined as the changes that are associated with the luteal phase of the menstrual cycle and that affect a woman's life in a regular and cyclical way, physically, emotionally and behaviorally.It is stated that PMS, which is very common in the society, affects close family relations, social life, work performance and work relations. The most common symptoms are; muscle, stomach and headache, breast tenderness, weight gain, intense desire for certain foods, appetite change, acne, edema, fatigue, mood swings, emotionality, irritability. It is known that the mental health of women who are physiologically affected by PMS will also be affected by the syndrome and bring along mental problems. Schmelzer stated in his study that the emergence of depressive thoughts and emotions in the premenstrual period is one of the most common PMS symptoms. In many studies examining the relationship between mental health and PMS, it has been found that there is a positive and significant relationship between PMS and depression level. One of these studies, Uran et al., in a study conducted with 55 people with an average age of 15, stated that the most common psychological factors accompanying PMS were irritability and anger level. As can be seen, PMS has negative effects on both mental health and physical health. Although many areas of women with PMS are negatively affected in their daily lives and its incidence is high, very few of them receive professional help and medical care. At the same time, their quality of life is also declining. It is known that women often resort to non‐pharmacological methods instead of receiving professional health care, since PMS is considered to be a physiologically normal condition with a traditional point of view.In addition, undesirable effects of medical treatments in coping with PMS are not preferred by women because they bring many health risks. Women can use many non‐invasive and risk‐free integrated treatment methods (such as heat treatments, exercise, aromatherapy, phytotherapy, Transcutaneous Electrical Nerve Stimulation, acupuncture, acupressure, yoga, progressive relaxation exercises, massage, relaxation techniques, reflexology, reiki) in coping with PMS. ) are more oriented. One of these methods, yoga, is a practice that includes deep breathing, meditation, stretching exercises and posture poses based on the unity of mind and body. It is emphasized that yoga exercises reverse the negative effects of stress on the immune system, improve inflammatory processes, reduce symptoms such as pain and insomnia, and improve quality of life, thanks to the balance, stretching, relaxation and strengthening components.In Yang and Kim's study with undergraduate nursing students with primary dysmenorrhea, a 60‐minute yoga program was applied once a week for 12 weeks. As a result of the study, it was determined that menstrual pain decreased significantly in the intervention group compared to the control group. Yonglitthipagon et al. found that yoga exercise applied to women with primary dysmenorrhea between the ages of 18‐22 for 30 minutes twice a week for 12 weeks reduced menstrual pain and increased physical fitness and quality of life. It has also been reported in studies that progressive relaxation exercises have a reducing effect on depression, stress and anxiety. Yoga and progressive relaxation exercises are seen as a valuable approach for the management of PMS, which is very common in young women and has significant negative effects on academic participation, social activities and quality of life. Although it is concluded that yoga and progressive relaxation exercises are an effective method n the treatment of PMS in a significant part of the studies in the literature, it is mentioned that the data are insufficient in terms of method and methodology and the necessity of studies that can support the results. In this study, it was aimed to determine the effects of yoga and progressive muscle relaxation exercises on menstrual symptoms, depression, anxiety and stress in university students with premenstrual syndrome.

Nct (2022). "Effectiveness and Cost-effectiveness of PelviSense, a Novel Biofeedback Device for Stress Urinary Incontinence in Women." ClinicalTrails.gov.
	Background Pelvic floor muscle (PFM) training (PFMT) is a common conservative first‐line treatment for SUI in women. However, the success of PFMT alone, without adjunctive therapies, has been hampered by the lack of training adherence among patients, who report the inability to contract the correct PFMs and limited motivation to perform PFMT exercises. Therefore, PFMT is often combined with adjunctive therapies, such as electromyography (EMG) biofeedback via an intravaginal probe (referred to as conventional biofeedback), transvaginal electrical stimulation (TVES), or weighted vaginal cones. However, PFMT adjunctive therapies that involve intravaginal probes/ cones are not preferred by women because they are invasive, and the vaginal insertion of probes/ cones can cause pain and discomfort. In addition, older women with atrophic vaginas have difficulty retaining probe/cones within the vaginal canal due to weak PFM tone. To meet the existing need for a non‐invasive PFMT adjunctive therapy, the research team developed the PelviSense. The PelviSense is an innovative, non‐invasive biofeedback device with wearable EMG sensors, designed to assist individuals in isolating and strengthening PFMs by helping them distinguish correct PFM contractions (lifting or squeezing the muscles) from incorrect attempts (bearing down). A mixed‐methods study, including a full‐scale RCT and semi‐structured focus groups, alongside an economic evaluation, will be conducted to evaluate both the effectiveness and cost‐effectiveness of the newly developed PelviSense device for the treatment of SUI in women. Aims: Aim 1: Investigate the efficacy of PelviSense‐assisted PFMT compared with PFMT alone for improving SUI symptom severity in women. Aim 2: Compare the cost‐effectiveness of the PelviSense device against PFMT alone for treating SUI in women. Aim 3: Explore the views of women regarding the use of the PelviSense device as an adjunct to PFMT and the impacts of the PelviSense device on their lives and well‐being. Methods Recruitment: Women with SUI who attend the outpatient Obstetrics and Gynecology Department of Kwong Wah Hospital (KWH) will be recruited for the study. In addition, potential participants will be recruited using a non‐probability convenience sampling technique through public, KWH, elderly care centers, and HK Polytechnic University (PolyU) campus advertising. Advertising will consist of study flyers posted at KWH, around the university campus, in waiting rooms of university health services and physiotherapy clinics, in community churches, and in university‐owned amenities, including sports centres and gyms. Randomisation and blinding: Computer‐generated randomisation will be utilised to ensure that both study groups are assigned an equal number of participants at a 1:1 ratio. Sequentially numbered, sealed, opaque envelopes of similar size and shape will be utilised to conceal group allocation and avoid selection bias. Due to the nature of the intervention, it is not possible to blind the therapists or participants to the allocation of treatment; therefore, only the outcome assessor will be blinded. To minimise detection bias, the outcome assessors will not participate in the treatment, and all study outcomes will be assessed in a separate room without any knowledge of participant allocation. Statistical analysis will be performed in a blinded manner, with each group assigned a code (group A and group B). The group identities will be revealed after all analyses are completed. Procedure and baseline assessment: Potentially eligible women who contact research personnel will be invited to attend an in‐person screening session. On this first day of contact, all women will undergo BMI measurement; complete the screening questionnaire, MMSE, and 1‐h pad test to confirm eligibility; and provide written informed consent. Baseline assessments of study outcomes will be performed, and eligible and consenting participants will be randomised to intervention groups. Outcome measures Outcomes assessments will b ompleted at baseline (time point 1 [T1]), 1‐month (T2) and 6‐months (T3). Intervention. The interventions will be provided for 6 months, beginning with a 1‐month supervised training period at KWH and PolyU. Following supervised training, women will be instructed to perform unsupervised home exercises for 5 months. Unsupervised home exercises will consist of at least eight contractions, performed 3 times per day, for 5 days of each week, with or without the biofeedback device according to group assignment. Each contraction will last for 10 seconds, followed by relaxation for 10 seconds. The PFMT exercise parameters are based on the National Institute for Health and Care Excellence PFMT guidelines for UI. Qualitative study (semi‐structured focus groups). A computer‐generated randomization schedule will be utilized to identify 20 participants (from the 71 participants included in the PelviSense‐assisted PFMT group) to participate in the focus groups. Each focus group will last for 45‐60 minutes. Focus groups will continue to be conducted until data saturation occurs. Focus groups will be scheduled for 8‐months post‐randomisation. A semi‐structured focus group approach will be used, during which discussion will be guided by but not limited to a set of pre‐determined, open‐ended questions. Data processing and analysis: Statistical analysis will be performed on an intention‐to‐treat basis using the Statistical Package for the Social Sciences (v.25; Armonk, NY). Treatment effects for both primary and secondary outcomes between T1, T2, and T3 and across the intervention groups will be evaluated using a two‐way analysis of covariance (ANCOVA) with age as the covariate. T1 and T2 will be compared to establish immediate treatment effects, and T1 and T3 will be compared to evaluate the retention of treatment effects. For significant group by time interaction effects, post‐hoc analysis using Bonferroni correction will be performed. The unadjusted mean total and disaggregated costs and differences in costs between the PelviSense and PFMT alone groups will be calculated. Seemingly unrelated regression (SUR) analyses will be used to estimate total cost differences (ΔC) and effect differences (ΔE). The EQ‐5D‐5L responses will be converted into utility scores to estimate the gain or loss of quality‐adjusted life‐years (QUALYs). The incremental cost‐effectiveness ratio (ICER) will be calculated using the formula ICER = ΔC / ΔE. Uncertainty surrounding ICERs and 95% confidence intervals for cost differences will be estimated using bias‐corrected and accelerated bootstrapping with 5,000 replications. Qualitative data from the focus groups will be analysed using the six phases of thematic analysis recommended by Braun and Clarke. The identified themes will then be defined and named according to their contents. The final set of themes will be confirmed as coherent and comprehensive by review of the team.

Nct (2022). "Effectiveness of a Manual Therapy Protocol on Women With Pelvic Pain Due to Endometriosis." ClinicalTrails.gov.
	Endometriosis is a debilitating disease with features of chronic inflammation that affects 10‐15% of women of reproductive age. Pelvic pain is one of the most common symptoms in women with endometriosis, and many of them report that it affects their quality of life. In addition, women with endometriosis, especially those with pelvic pain, also have an increased vulnerability to various psychiatric disorders, such as depression and anxiety. In this context, physical therapy can contribute to the multidisciplinary assessment and treatment of pelvic pain. In addition, manual therapy could improve certain variables related to central sensitization, such as inhibitory pain regulation and neuronal excitability in the dorsal horn of the medulla, in patients with chronic pain. Some prospective studies have applied manual therapy in patients with pelvic pain due to endometriosis, and have shown a trend towards improvement of pain and quality of life. Moreover, it is considered a well‐tolerated and accepted treatment by patients. However, to date, it has not been investigated whether the application of a manual therapy protocol improves pelvic pain and other endometriosis‐associated symptoms, lumbar mobility, medication intake, depression and anxiety levels, and quality of life in women with endometriosis‐associated pelvic pain compared to a placebo treatment. Therefore, this is a randomized clinical trial in which two groups of twenty people in each group will participate, with different interventions: ‐ Experimental group: manual therapy protocol. ‐ Placebo group: placebo treatment. Participants will be evaluated in four moments, at baseline, post‐intervention, 1‐month follow‐up and 6‐month follow‐up. Data analysis will be performed with SPSS statistic program (v24). Normality and homoscedasticity will be analyzed by Shapiro‐Wilk t‐test and Levene test, respectively. Multifactorial ANOVA will be performed with two groups (experimental and placebo group) and four‐time assessments. For comparation between groups Bonferroni will be used. When p<0.05 statistically significant differences will be assumed.

Nct (2022). "Effects of Antenatal Exercises With Sacroiliac Joint Mobilization in Pregnancy Related Pelvic Girdle Pain." ClinicalTrails.gov.
	Pelvic girdle pain is defined as the pain experienced between the posterior iliac crest and the gluteal region, particularly in the sacro iliac joint.It is characterized by pain, instability, limitations in mobility and functioning of the pelvic region.This condition is found to be associated with difficulties in activities of daily life such as standing, walking, working and sleeping hence, affecting the quality of life.Pelvic girdle pain is on of the major preganacy‐related problems that affects about 50% of the pregnant females.Previous studies have shown that about 33‐50% of the women repost pelvic girdle pain before 20 weeks of gestation and the the prevalavce may reach 60‐70% in late pregnancy.Different management strategies including antenatal exercises, sacro iliac joint belt, kinesiotaping, sacro iliac joint mobilization etc are used to treat pelvic girdle pain.Different studies have shown the positive results of antenatal exercises, sacro iliac joint belt and kinesiotaping but there is dearth of evidence to establish the efficacy of sacro iliac joint mobilization on pregnancy‐related pelvic girdle pain.This study aims to fulfill this gap by comparing the effects of antenatal exercises with sacro iliac joint mobilization on pelvic pain, function and disability. This randomized control trial will be conducted in Obs&Gynae Opd of Fauji Foundation Hospital using non‐probability purposive sampling.Participants will be briefed regarding the study objectives, procedure, risks and benefits of treament, voluntary participation and right to withdraw.Written informed consent will be taken from all the participants before conducting the research.Details of exercise program will be explained to them.Screening will be done by using PAR Q.Dignostic tests will be applied to confirm the pelvic girdle pain.FABERs test and Posterior Pelvic Pain Provocation test will be used for this purpose.Then the selected participants will be randomized into 2 groups(experimental group and control group)via lottery method. Participants will complete Numeric Rating Pain Scale(NRPS) for pain, Pelvic Girdle Questionnaire for disability measurement and will perform Active Straight Leg raise test(ASLR) to measure pelvic function.All of these measurements will be taken at baseline, after 2 weeks and then after 4 weeks of intervention. The treatment protocol of both groups is as follows: Group 1(Control group):Postural education, hot pack, antenatal exercises(i.e deep breathing, stretching, kegel exercises, Mitchells physiologic relaxation technique and walk. Group 2(Experimental group):Postural ecucation, hot pack, antenatal exercises(i.e deep breathing, stretching, kegel exercises, Mitchells physiologic relaxation technique and walk) and sacro iliac joint mobilization in side lying position(1 set of 30 oscillatios per session)

Nct (2022). "Effects of Assisted Sit-up Exercise vs Swiss Ball Pikes on Postpartum Low Back Pain." ClinicalTrails.gov.
	This study will be a randomized clinical trial. Subjects with postpartum low back pain meeting the predetermined inclusion and exclusion criteria will divide into two groups. Pre‐assessment will be done using the Numeric Pain Rating Scale & Roland‐Morris Questionnaire as subjective measurements. Subjects in one group will be treated with assisted sit‐up exercise and the other will be treated with swiss ball pikes. Each subject will receive a total of 12 treatment sessions, with 2 treatment sessions per week. Post‐treatment reading for numeric pain rating scale and Roland‐Morris questionnaire will be recorded after the end of the 4th, 8th, and 12th treatment session.

Nct (2022). "Effects of Connective Tissue Manipulation Versus Stretching Exercises in Primary Dysmenorrhea." ClinicalTrails.gov.
	The study will be a randomized clinical trial in which the effect of connective tissue manipulation will be compared with the effect of stretching exercises on pain and severity of symptoms in primary dysmenorrhea. Inclusion criteria will include nulliparous females in the age range of 18‐25 years old. Exclusion criteria will be women with irregular menses (<21 and >35 days), systemic and gynecological diseases (gastrointestinal, autoimmune, psychiatric diseases, endometriosis, pelvic inflammatory diseases), pregnant women, previous pelvic surgery, traumatic injury. The participants will be allocated to two groups, group A and B. Group A will receive connective tissue manipulation on sacral, lumbar, lower thoracic and anterior pelvic regions with the patient in sitting and supine positions. Group B will receive active stretching exercise regime including forward, backward ad side trunk bending, heel raise, half squatting, knee to chest, hamstring stretching, calf stretching and abdominal contractions. All the participants will be informed about the manner of research and will be asked to sign the consent form after they are willing to participate in the study. WaLIDD score and dysmenorrhea severity scoring will be used to determine and assess the dysmenorrhea pain and severity. Treatment sessions will be conducted for 8 weeks, 3 times in a week and each session will be carried out for 20 minutes. At the end of two months, subjects will be assessed for their two menstrual cycles. SPSS 21 will be used for data analysis. After checking normality of data appropriate tests will be applied.

Nct (2022). "Effects of Dry Heat Application for Menstrual Symptoms." ClinicalTrails.gov.
	The study was conducted as a randomized controlled trial, a non‐blinded between 30 September 2019 and 29 November 2019. In the first stage of the present study, the Premenstrual Syndrome Scale was used for all participants and the study was continued with the students with premenstrual syndrome symptoms based on the data acquired from the Premenstrual Syndrome Scale. This stage was used only for restricting the sample group, rather than diagnosing or treating the students. In the second stage, the randomization of students included in the sample group was presented according to the CONSORT diagram. The population of the study consisted of 452 female nursing students studying in the faculty of health sciences in a university. The students (n=75) who were absent in the school, took analgesics during the study, and did not agree to participate in the study, were excluded from the study. The students, who had no diagnosis of psychiatric disorder and history of endometriosis, stated that they menstruated regularly (between 22‐35 days), did not use complementary and alternative treatments such as analgesics or massage throughout the study, had no diabetes or neuropathic problem causing nerve injury, did not take oral contraceptives, were over 18 years, and agreed to participate in the study, were included in the study.

Nct (2022). "The Effects of Exercise and Probiotics on Dysmenorrhea and Microbiome." ClinicalTrails.gov.
	In current study, there were two stages designed for current study. The definition of dysmenorrhea population depended on the Visual Analogue Scale (VAS) of McGill Pain Questionnaire (more than 5) and the VAS score less than 2 was considered as non‐dysmenorrhea population. In the first stage, the 20 subjects were recruit for non‐dysmenorrhea group (Control group) and other 60 subjects were randomly allocated into three group with original lifestyle, aerobic, and resistant exercise intervention (Dys‐Control, Dys‐Aerobic, and Dys‐resistant groups). The questionnaires (Premenstrual syndrome, the Menstrual Distress, and McGill Pain), body composition, physical fitness, biochemistries, inflammation, hormones and microbiome analysis (feces and tampon) were evaluated and assessed before and after 10‐weeks indicated exercise training. In the second stage, one hundred subjects (20 non‐dysmenorrhea and 80 dysmenorrhea populations) will be recruited and the dysmenorrhea will be randomly allocated into Dys‐Control, Dys‐probiotics, Dys‐exercise and Dys‐probiotics and exercise groups. The questionnaires (Premenstrual syndrome, the Menstrual Distress, and McGill Pain), body composition, physical fitness, biochemistries, inflammation, hormones and microbiome analysis (feces and tampon) were evaluated and assessed before and after 10‐weeks indicated interventions (probiotics and exercise).

Nct (2022). "Effects of Flourish HEC and BioGenesis to Improve Conception." ClinicalTrails.gov.
	Disrupted vaginal microbiomes are associated with a number of poor reproductive outcomes, including infertility, miscarriage, premature rupture of membranes, preterm labor and delivery, delivery of a low birthweight baby, and maternal infections (chorioamnionitis, endometritis). A healthy vaginal microbiome is typically thought to be one that is dominated by one of several Lactobacillus species, such as L. crispatus, L. gasseri, or L. jensenii. Several studies have shown that non‐lactobacilli‐dominant biomes are associated with poor in vitro fertilization or intrauterine insemination outcomes. Fewer studies have examined fertility in the home setting, and none to date has asked whether improving the vaginal microbiome (VMB) could increase fertility. This study addresses both. By assessing the VMB before and after using a vaginal care system which supports a healthy VMB, we will be able to examine whether there are associations between VMB composition and infertility, and whether shifting the VMB toward a lactobacillus‐dominant state is able to improve chances of conception. In this study, women will either follow routine care (control) or routine care plus the vaginal care system and fertility lubricant (intervention) for 3 months or until becoming pregnant, whichever comes first. In addition to tracking conception rates during those 3 months, we will follow women for an additional year following completion of the 3‐month timeframe. If any woman is pregnant at the one‐year mark, her pregnancy will be followed until delivery (or early termination) to track delivery outcomes and adverse events.

Nct (2022). "Effects of Flourish HEC on Localized Provoked Vulvodynia." ClinicalTrails.gov.
	Vulvodynia is a chronic pain condition affecting the tissues of the external genitalia in women. Localized provoked vulvodynia (LPV) is a specific subset of vulvodynia in which pain occurs upon touching specific sites on the vestibule (or, less commonly, another defined area), and which has been present for more than three months without a known cause. LPV is characterized both by allodynia (pain in response to a normally non‐painful stimulus) and hyperalgesia (excessive pain response), leading to pain with sex, tampon use, and even with activities of daily life, such as sitting or wearing tight clothing. It is becoming accepted that LPV occurs as a type of hypersensitivity to Candida and other antigens which occurs in susceptible women. LPV is an inflammatory condition with increased levels of B‐cells, T‐cells, and macrophages in tender areas vs. non‐tender areas. The inflammatory process sparks neuroproliferation ‐ growth of new nerve endings ‐ which increases the density of nerve fibers in tender spots, especially in areas of lymphoid aggregates. The vulvar and vaginal microbiomes are connected to each other; species found in one are often found in the other. In fact, Jayaram et al. showed that all vaginal species were also found on the vestibule, and the dominant vaginal species is also the dominant vestibular species, suggesting that vaginal secretions are a major contributor to the vestibular/vulvar microbiome. Three recent studies have examined the link between vulvodynia and the vaginal microbiome. Results vary by study, with one showing differences in the present vaginal microbiomes between women with vulvodynia and healthy women, and others not showing differences. These may be explainable by inclusion/exclusion criteria (two studies excluded women with active yeast infection; one study specified studying generalized, not localized, vulvodynia; while the others did not specify). But it is agreed that past alterations in the microbiome primed women for excessive pain in response to gentle stimuli. Vaginal microbiome composition is known to affect immune activation in the vagina and vulva. Campisciano and colleagues showed that vaginal dysbiosis is associated with elevated levels of interleukin (IL)‐1ra and IL‐2, and lower levels of fibroblast growth factor (FGF)‐beta and granulocyte‐macrophage colony stimulating factor (GM‐CSF) than observed in healthy vaginas. Another study by the same group reported associations between vaginal microbiome composition and IL‐1alpha and IL‐18. Doerflinger showed activation of the innate immune response by Lactobacillus iners (intermediate flora) and Fannyhessea vaginae (associated with bacterial vaginosis), but not L. crispatus (healthy flora). Of greatest relevance, Falsetta and colleagues investigated expression and activation of the toll‐like receptor family and found seven of them to be expressed at higher levels in tissue biospies from tender spots in LPV than in control tissue, and that exposure to HIV increased expression of TLR7 expression and the downstream inflammatory molecule IL‐6. Notably, no studies have examined whether improving the vaginal microbiome might lead to reductions in immune signaling in vulvodynia. Taken together, it is reasonable to hypothesize that the constitution of the vaginal microbiome may influence the hypersensitivity to allergens that comprises the cause of LPV. It is also possible that improving the vaginal microbiome may reduce immune cell recruitment and activation, reducing pain. It is predicted that using sequencing‐based technology, differences between the vaginal microbiomes of women with LPV and those without will be detectable. Furthermore, its is predicted that using an over‐the‐counter feminine hygiene system designed to support a healthy vulvovaginal microbiome will reduce pain in women with LPV over and above any reductions observed with standard‐of‐care treatment. The investigators recently conducted an 11‐week pilot study of similar design. Women with recurrent bacterial vaginos (BV) were recruited to use the Flourish Vaginal Care System® for 11 weeks. Primary outcomes were vaginal fluid pH and whether or not women had BV recurrence. By the end of the study, the average vaginal fluid pH had fallen from mean (SD) of 4.54 (0.53) at week 0 to 4.08 (0.40) at week 11. At baseline, 30% of women had active BV. (These women were treated with standard of care oral metronidazole). The number of BV‐positive women steadily declined until 5 weeks, at which point no woman had BV. There was no recurrence of BV in any woman through the end of the study. Women reported fewer vulvovaginal symptoms throughout the study. An ad hoc follow‐up phone survey a year later showed that only one participant had a recurrence of BV since the end of the study. This study shows that the system we propose to use in the present study is able to effect positive changes in the vaginal microbiome. A follow‐up trial at the same center examining the vaginal microbiome using the same system for 6 months has shown very low recurrence rates, based on preliminary analysis, less than 20% in 6 months, compared with other studies showing 3‐month recurrence rates of 43% or 62%. This study, which has completed data collection but has not yet been published, also showed that the vaginal microbiome was in a healthy or intermediate community state type (CST; not BV) during use of the system, though it took over 5 weeks of usage for one woman to move from a BV‐like CST to a healthy CST. A similar study is underway using the "Flourish HEC" system ‐ a nearly identical kit with a different vaginal moisturizing gel, gentler for those with sensitivities. To date, five participants are enrolled, and only the initial microbiome tests are available. However, study subjects are reporting that they are feeling good while using the system. It is this Flourish HEC system that will be tested in the present study. We emphasize that the vaginal care system is not intended to modify the body; it has no active drug components. Instead, it is a hygiene system that mimics the proper vaginal environment for a healthy microbiome to develop and thrive. The investigators hypothesize that regular use of the Flourish HEC Vaginal Care System by women with LPV for three months will colonize the vagina and vulva with healthy bacteria, and that this will reduce inflammation, immune system activation, and neuroproliferation, ultimately reducing pain.

Nct (2022). "Effects of HIA and PCE in Primary Dysmenorrhea." ClinicalTrails.gov.
	There are less research on effectiveness of pelvic clock exercises in dysmenorrhea they are very less evidence and less documented in literature.. Although there are many researches on high intensity aerobics.Previous researches only have lierature about aerobics.So to address this literature gap, conduct a prospective randomized controlled trial to investigate the effects of high intensity aerobics and pelvic clock exercises in primary dysmenorrhea.

Nct (2022). "Effects of Hypopressive Exercises in Comparison With Routine Pelvic Floor Exercises in Women With Urinary Incontinence." ClinicalTrails.gov.
	A randomized control trial study will be conducted in which patients with urinary incontinence will be assigned to group 1 that will receive hypopressive exercises with electrical muscle stimulation (EMS) and patients in group 2 will receive pelvic floor exercises with EMS. The intervention will be applied (3 days/week) for 8 weeks. Four sets of 10 repetitions with a 3‐minute interval between each set will be performed for group 1 in an upright position while four sets of 10 repetitions with a 2‐minute interval between each set will be performed for group 2 in the sitting position.

Nct (2022). "Effects of Kinesiotaping With and Without Pelvic Tilts in Dysmenorrhea." ClinicalTrails.gov.
	This study will be a randomized controlled trial to compare the effectiveness of kinesiotaping with and without pelvic tilts in subjects with primary dysmenorrhea. Subjects with primary dysmenorrhea meeting the predetermined eligibility criteria will be divided into two groups using the random sequence generation method. Pre‐intervention responses shall be taken during the first menstrual cycle using the Numeric Pain Rating Scale, WaLLID tool & Menstrual Distress Questionnaire. Subjects in Group A shall be treated with kinesiotaping and pelvic tilts while subjects in Group B shall be treated with kinesiotaping only. Each subject will receive 02 treatment sessions during the second & third menstrual cycles. Post‐intervention responses shall be recorded in the fourth menstrual cycle using the Numeric Pain Rating Scale, WaLLID tool & Menstrual Distress Questionnaire.

Nct (2022). "The Effects of Making Pregnant Women With Preterm Birth Threat Watch Nature Images With Virtual Reality Goggles on the Levels of Stress, Anxiety, Attachment, and Care Satisfaction." ClinicalTrails.gov.
	Virtual reality application, which is a non‐pharmacological method, is used for different purposes in many different fields. One of the areas where virtual reality application is used is health services. Its use in the field of obstetrics is new. Virtual reality application is often in pregnancy; it is used to reduce pain, stress and anxiety levels, exercise training and train pregnant women to effectively manage their pain during childbirth. Although pregnancy is a normal physiological process, adverse situations may occur that can make every pregnancy risky. Threatened premature birth, which is called the onset of uterine contractions without cervical changes between the 20th and 37th weeks of pregnancy, is also among these risk groups. Pregnant women diagnosed with the threat of premature birth are usually treated by hospitalization. Psychological problems such as stress, fear and anxiety may develop in pregnant women who are on bed rest in the hospital. In these pregnant women, mother‐infant attachment may also be adversely affected. Pregnant women who are hospitalized and taken to bed rest due to risky pregnancy need to be informed and supported by health personnel. The midwife's spending enough time with the pregnant woman, keeping in touch and meeting her needs increase satisfaction in terms of care. When the literature was examined, it was determined that pregnant women were satisfied with the virtual reality application and thus increased care satisfaction. In the literature, there is no study using virtual reality glasses in pregnant women diagnosed with preterm birth threat. For this reason, this study was planned to determine the effect of watching nature images with virtual reality glasses on the level of stress, anxiety, attachment and care satisfaction to pregnant women diagnosed with preterm birth threat.

Nct (2022). "The Effects of Manual Lymphatic Drainage and Transcutaneous Electrical Nerve Stimulation in Premenstrual Syndrome." ClinicalTrails.gov.
	The aim of this study is to (a) investigate the effects of manual lymphatic drainage and transcutaneous electrical nerve stimulation on the severity of syndrome symptoms, pain, heart rate variability, and quality of life in women with premenstrual syndrome, and (b) compare the effectiveness of these two methods. Female participants who met the inclusion criteria and volunteered to participate in the study will be called approximately one week before menstruation. After the participants are randomly divided into 3 groups, their baseline assessments will be made. Then, the participants will be treated according to the group they are assigned to. Treatments will be applied for 5 days and once a day. No treatment will be applied to the control group. The assessments will be repeated after the treatment, on 1st day of menstruation, two days before the next menstruation, and on the first day of the next menstruation. The hypothesis of this study is that manual lymphatic drainage and transcutaneous electrical nerve stimulation have positive effects on the severity of premenstrual syndrome symptoms, pain, heart rate variability, and quality of life.

Nct (2022). "Effects of Muscle Energy Technique Versus Aerobic Exercises on Pain and Disability in Patients With Chronic Pelvic Pain." ClinicalTrails.gov.
	The aim of study is to find out the effects of muscle energy technique versus aerobic exercises on pain and disability in patients with chronic pelvic pain.

Nct (2022). "Effects of Pelvic Floor Health Education Program in Women With Stress Urinary Incontinence." ClinicalTrails.gov.
	Stress urinary incontinence (SUI) is the involuntary urinary incontinence that develops in parallel with the increase in intra‐abdominal pressure and is seen in the absence of detrusor contraction. Studies have shown that SUI, leading to a decrease in the quality of life and worsening of social and health conditions, is more common in women than men. Knowledge of pelvic floor health or urinary incontinence is generally low. Low level of knowledge or wrong information limits patients' access to treatment. Pelvic floor muscle exercise and lifestyle recommendations are also the first treatment options for SUI. The information and awareness related to the pelvic floor and SUI can be increase and unhealthy behavioral strategies can be modifiable through education programs. Therefore the education programs related to the pelvic floor health would have positive effects on urinary incontinence symptoms, knowledge level and quality of life. Studies about this issue are needed.

Nct (2022). "The Effects of PFMT and MPE in Elderly Women With SUI." ClinicalTrails.gov.
	Stress Urinary Incontinence (SUI) is associated with situations which bladder pressure exceeds the pressure at which the urethra has the capacity to remain closed, such as physical exertion, coughing, and sneezing. SUI is more predominant in women worldwide, with a prevalence ranging from 10% in young women to 45% in the elderly. Physiotherapy interventions in SUI include patient education including recommendations for bladder and/or bowel training, fluid management, and diet modification; modalities for decrease pain; pelvic floor muscle training (PFMT) with or without biofeedback and/or electrical stimulation to improve strength and coordination of the pelvic floor muscle (PFM) and stabilization exercises to improve strength of abdominal and/or lumbar stabilizer muscles. PFMT includes repetitive contraction of the PFM, which increases perineal support and improves the muscle tone of the PFM. Modified pilates exercises (MPE) is a mind‐body approach that includes slow, controlled movements that focus on posture and breathing. The aim of the study was to compare the effects of PFMT and MPE on SUI frequency and explosure from symptoms, PFM activation response and strength of lumbar stabilizing muscle in elderly women with SUI. In this study, thirty‐four elderly women who were diagnosed with SUI were randomized into Group 1: PFMT (n=17) or Group 2: MPE (n=17). Both groups performed their exercises twice a week for 12 weeks and accompanied by a physiotherapist. Incontinence Severity Index (ISI), Urogenital Distress Inventory‐Short Form (UDI‐6) and Incontinence Impact Questionnaire‐Short Form (IIQ‐7) were used to assess SUI frequency and explosure from symptoms, electromyography (EMG) device was used to assess PFM activation response and a stabilizer was used to assess strength of lumbar stabilizing muscle. The assessments were performed at baseline and after 12 week treatment. The effect size was calculated for the assessments used in the study.

Nct (2022). "Effects of Pilates Exercises on Postpartum." ClinicalTrails.gov.
	The investigators conducted the study at Ankara Medipol University, Faculty of Health Sciences, Department of Physical Therapy and Rehabilitation. This study was conducted by the principles set out in the Declaration of Helsinki. Fifty postpartum women aged 25‐38 will be included in the study. ‐ Procedures The investigators assessed the participants by an experienced physiotherapist, who was blind to the randomization, at the start of the study and after the 8‐week training. The group on which they depended was not disclosed to the participants until the end of the baseline evaluation. The investigators used a computer program for randomization and randomly placed individuals who completed the initial assessment into the pilates group (PG) or control group (CG). The investigators performed the Pilates exercises under the supervision of a certified physiotherapist with ten years of experience. The investigators asked the individuals not to inform the evaluator of their involvement in the training during the last evaluation. Before the study, the investigators explained the purpose and content of the survey to the participants and obtained written informed consent from all pregnant women to participate in the study. Pilates training was done by an Australian Pilates and Physiotherapy Institute certified and experienced Ph.D. Physiotherapist Halil Ibrahim Bulguroglu lasted eight weeks, two days a week for one h. The investigators divided the individuals in the Pilates exercise group into two smaller groups of 12 or 13 to verify whether they correctly did the exercises. In this study, the investigators organized a program to include 15 min of warm‐up, 30 min of Pilates exercises, and 15 min of cooling and stretching exercises. The exercises were done in 10 repetitions. The exercise program recommended by the Australian Pilates and Physiotherapy Institute during postpartum was used in training. During the Pilates exercises, investigators described the activities with different visual simulation techniques, and exercises were done together with Pilates breathing. The intensity of the exercises was increased by using different positions and elastic bands. The resistance was increased by starting with the red Therabant and switching to the blue band after two weeks. If the new resistance amount was challenging for the patient, the exercises were continued with the same color band for one more week. Stretching exercises and posture exercises were used during the cooling period. The subjects in the online pilates group were informed about side effects such as shortness of breath, dizziness, headache, muscle pain, and weakness. They were asked to stop exercising when there were any side effects. ‐Statistical analysis The investigators will perform statistical analysis using SPSS software, version 21 (SPSS Inc. Chicago, IL, USA). The normal distribution of variables will be determined using histograms, probability plots, and a Shapiro‐Wilk test. Because of an abnormal distribution, median and interquartile range (IQR) were used for descriptive statistics. Numerical variables showing normal distribution were shown as mean±standard deviation. The investigators will use a Mann‐Whitney U test to compare baseline and change values between groups. The investigators will use Wilcoxon Test to compare baseline values within the group and values after eight weeks. The significance level will be set at p < 0.05 for all analyses.

Nct (2022). "THE EFFECTS OF PREVENTION PROGRAM ON LOW BACK PAIN AND QUALITY OF LIFE DURING PREGNANCY." ClinicalTrails.gov.
	Although pregnancy is a natural process, it is a period in which some bio‐physiological changes are experienced. These changes cause low back pain by affecting the musculoskeletal system as well as the endocrine, cardiovascular and renal systems. Pregnancy‐related low back pain is defined as recurrent pain in the lumbopelvic region lasting more than one week. Low back pain in pregnancy has been known for centuries and was described in ancient times by physicians such as Hippocrates, Vesalius, Pinean, Hunter, and Velpeau. Walde distinguished between pelvic pain and lumbar pain for the first time in 1962. It can manifest itself in pregnancy as low back pain, lumbar pain, pelvic pain and lumbopelvic pain where both are present. Low back pain in pregnancy is usually 20‐28. Although it can be seen in the first trimester of pregnancy, it can also be seen in the first trimester. 40% of women who experience low back pain during pregnancy continue to experience pain for 6 months postpartum, 30% for 12 months postpartum, and 10% for 24 months postpartum. In the literature, the prevalence of low back pain, which is very common during pregnancy, is reported to be 25‐90%. In the literature, reported low back pain in pregnancy as 76.6% in a study conducted in Ontario. In the literature, reported the prevalence of low back pain in pregnancy as 83.5% in another study conducted in Pakistan. Although studies on the prevalence of low back pain in pregnancy are limited in our country, prevalance reported of low back pain during pregnancy was 53.93% in a study conducted in the province of Ağrı. In another study conducted in Kayseri this rate was reported as 54.1%. In another study reported the prevalence of low back pain as 75.3% in the study conducted in Kastamonu. The etiology of low back pain in pregnancy is multifactorial and generally depends on hormonal, metabolic and vascular changes. In addition, many factors such as genetic factors, increased parity, postural changes, body mass index, smoking, sedentary lifestyle, stressful life, infection, history of low back pain in previous pregnancy, history of low back pain before pregnancy, working in a strenuous job create risk. It is stated in the literature that low back pain during pregnancy affects women's quality of life negatively. Decreased physical activity with low back pain causes social and economic problems by bringing anxiety and depression. It is reported in the literature that low back pain experienced during pregnancy reduces the quality of life by having a negative effect on physical activity, personal care, sleep quality, social life, work life, sexual life, energy and mood. In a study to examine the quality of life of women with low back pain during pregnancy, it was reported that women with low back pain during pregnancy had lower physical, mental and social scores, and their quality of life decreased as the severity of pain increased. Low back pain experienced during pregnancy is seen as a part of pregnancy by both women and health professionals, and is neglected on the grounds that it does not pose a serious risk for the mother and baby. However, low back pain experienced during pregnancy negatively affects the quality of life, can be permanent in the postpartum period and cause postpartum depression. In order to cope with low back pain in pregnancy and to increase the quality of life, low back pain should be evaluated in antenatal and postnatal follow‐ups.Risk factors should be examined, women in the risk group should be identified, their low back pain experience should be questioned, prevention and coping strategies and the effects of low back pain on their quality of life should be evaluated. Healthy lifestyle programs should be developed to help prevent low back pain and develop coping strategies for pregnant women with low back pain. Within the healthy lifestyle program; Providing the right posture, providing ideal weight gain during pregnancy and preventing constipation, individual nutrition education, prevention of urinary tract infections, heal y sexual life, regulation of activity, position change, ergonomics training, adequate rest, appropriate shoe selection, smoking cessation, stress management, non It should contribute to reducing low back pain and increasing the quality of life by including pharmacological methods of coping with pain. Pender's Health Promotion Model guides the planning, implementation and evaluation of health protection and promotion behaviors. Pender's Health Promotion Model will be a guide in the counseling that nurses will give on the prevention of low back pain in pregnancy and the development of strategies to cope with low back pain.

Nct (2022). "Effects of Silver Spike Point Therapy on Pelvic Girdle Pain PAIN." ClinicalTrails.gov.
	This study will be a randomized clinical trial that will investigate the effectiveness of silver spike point therapy and manual therapy in subjects with pregnancy‐related pelvic girdle pain. Subjects with pregnancy‐related pelvic girdle pain meeting the predetermined inclusion & exclusion criteria will be divided into two groups using the lottery method. Pre‐assessment will be done using NPRS and PGPQ as subjective measurements and PSFS as objective measurements. Subjects in one group will be treated with silver spike point therapy and manual therapy, the other will be treated with manual therapy only. Each subject will receive 10 treatment sessions, with 05 treatment sessions per week. Post‐treatment reading for NPRS, PGPQ, and PSFS will be recorded after the end of the 10th treatment session. Recorded values will be analyzed for any significant difference between pre and post‐treatment values SPSS 21.

Nct (2022). "Effects of Transcutaneous Tibial Nerve Stimulation for Overactive Bladder Symptoms in Adults." ClinicalTrails.gov.
	For overactive bladder symptoms, there are numerous physiotherapy techniques have been found to be beneficial. Transcutaneous electrical stimulation of the tibial nerve is one of those treatment options, that is entirely a non‐invasive, easy to apply, and cost‐effective technique. Transcutaneous stimulation of the tibial nerve targets the sacral nerve plexus that contracts the pelvic floor muscles and controls the bladder function. This research aims to study the effectiveness of transcutaneous tibial nerve stimulation in adults with overactive bladder symptoms along with the conventional physiotherapy for overactive bladder (pelvic floor muscle training through Kegel's exercises) among 60 patients with overactive bladder symptoms on the basis of non‐probability purposive sampling technique with screening for study criteria through a consultant urologist. After taking informed consent, all participants will be randomly allocated into two groups. Group A will receive pelvic floor muscles training through Kegels exercises along with transcutaneous electrical stimulation of the tibial nerve and Group B will receive pelvic floor muscles training through Kegels exercises. The treatment duration will of six weeks. Outcomes will be assessed before the start of the treatment and after the end of the treatment sessions.

Nct (2022). "Effects of Virtual Reality and Nature Sounds on Pain and Anxiety During Hysterosalpingography." ClinicalTrails.gov.
	Infertility treatment is a stressful and anxious process that begins when couples are diagnosed with infertility. Although this process may seem like a simple medical intervention, the treatment stages affect the couple in many ways when it is deepened. Infertility treatment is a process that requires the active participation of couples against emotional and physical difficulties. The treatment process is a period in which couples should be in constant communication with healthcare professionals, as well as intensive routine and surgical procedures.In this process, medical and surgical treatment methods are used. In the literature, it is stated that 85‐90% of the problems that cause infertility are solved with medical and surgical treatment. In the evaluation of infertile couples, hysterosalpingography (HSG) is a invasive radiologic procedure to visualize uterine cavity and tubes after contrast enhancement. HSG plays an important diagnostic role in finding the cause of infertility and in deciding the line of management.The aim of this study is to demonstrate the effects of virtual reality and nature sounds on pain and anxiety during hysterosalpingography. This randomized controlled study will conduct at Ondokuz Mayıs University Training and Research Hospital, Obstetrics and Gynecology polyclinic between February 2022 and August 2022. Volunteer women undergoing HSG as part of infertility evaluation will be includ. Participants will randomly assigned to the Virtual Reality and nature sounds intervention, nature sounds intervention or the control group using a computer‐generated list. A data collection form including socio‐demographic and obstetric characteristics such as age, educational status, place to live, duration of infertility, previous pregnancies, births, abortion/curettage numbers, Spielberger State Anxiety Scale and Visual Analog Scale for pain and Visual Analog Scales for satisfaction will use for each patient. After obtaining written informed consent, the data collection form, Spielberger State Anxiety Scale and VAS pain scoring scale will be applied to both groups by face to face interview during the day giving appointment for HSG. Immediately after the questionnaires were applied, the nurse gave virtual reality glasses and headphone to intervention group for before HSG and while HSG totally 30 minutes. The nurse gave to nature sounds intervention group headphone. After the groups will formed, a nature‐based sound will listen to the women in the nature sounds group before and during the HSG procedure. Listening to nature‐based sound will perform for a total of 15 minutes half an hour before the HSG procedure, and for 15 minutes during the procedure, for a total of 30 minutes. Participants in the control group received standard care (verbal information about procedure and a short written information about the procedure) and no intervention (nature sounds or virtual reality) will perform.The IBM SPSS (Statistical package for the Social Sciences) 23.0 package program will use to evaluate the data obtained in the study.

Nct (2022). "EFFICACY AND SAFETY OF OVA AND LAVAGE MEDICAL DEVICES IN THE TREATMENT OF NON-SPECIFIC VULVOVAGINITIS." ClinicalTrails.gov.
	To evaluate and compare the efficacy, activity and tolerability of a vaginal ova formulation containing tindalised cultures (Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus plantarum, Streptococcus thermophilus) (LOGUSGYN/CANDIDEP OVULES) and in vaginal lavage (LOGUSGYN/CANDIDEP LAVENDER) in patients with nonspecific vulvovaginitis compared to sterile saline‐based vaginal irrigation (AELAV PURLING). The primary efficacy endpoint is based on the percentage of patients with therapeutic success, defined as resolution of signs and symptoms of vaginitis (total symptom score <4) at the end of treatment. For the overall assessment of clinical outcomes (resolution, improvement or failure): outcomes at the end of treatment will be considered. The treatment outcome will be measured after 5 days (V2) and after 10 days of treatment (V3) for groups A, B and C Also for group D (later, with a second randomisation, divided into groups E and F) the primary endpoint will be the same as for groups A, B, C at the visit after 30 days of treatment (V4) The treatment outcome will be measured after 5 days (V2) (after 10 days (V3) of treatment the SPT result will be re‐evaluated and will be included in the secondary endpoints). The evolution of signs and symptoms of vaginitis is defined as the percentage of patients with resolution (overall score 4), improvement (decrease in overall score from baseline of 50%) or failure (decrease in overall score <50%). Ninety‐one adult female subjects (aged 18‐65 years) with a diagnosis of vulvovaginitis and the presence of at least two subjective symptoms and two objective signs (at least moderate) of vaginal inflammation were recruited. The study was planned with a randomised, controlled, parallel‐group sequential design to test a vaginal ova formulation containing tindalised cultures (Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus plantarum, Streptococcus thermophilus) (LOGUSGYN/CANDIDEP OVULES) and vaginal douches (LOGUSGYN/CANDIDEP LAVENDER) in patients with non‐specific vulvovaginitis to control treatment (AELAV PURLING‐ vaginal irrigation with sterile saline). The sequential design involves a first phase with randomisation into 4 groups (A, B, C, D) followed by a second randomisation of group D (patients with vulvovaginitis and positive for HPV at PAP test) into two subgroups (E and F). The primary efficacy endpoint is based on the resolution of vulvovaginitis signs and symptoms (total SPT symptom score at the end of the first Phase I treatment period (after 5 days of treatment) for groups A, B, C and D). For the overall assessment of clinical outcomes (resolution, improvement or failure): results at the end of treatment after 10 days (V3) will be considered as secondary endpoints. Phase II will always have the resolution of vulvovaginitis signs and symptoms (total SPT symptom score f4 at the end of treatment at 30 days (V4)) as the primary endpoint, compared to Phase I results in group D. The protocol involves 4 visits per patient over 10 days for the groups. For groups E and F only the visit at V4 after 30 days of treatment. At visit 1 (0 days, baseline visit), patients will have to sign a written informed consent before performing any procedure. Subjects will be screened for study eligibility, verifying that all inclusion criteria and no exclusion criteria are met. At V1, the investigator will collect demographic and anamnestic data and perform a vaginal swab; in case of specific growth of pathogenic organisms, patients will be treated after the 5‐day follow‐up visit with antibiotics or antimycotics according to the result of the antibiogram. Delivery of the information note to the GP and the study and treatment information sheet to the patient. The investigator will then assess subjective symptomatology (burning, pain, itching, vaginal dryness, dyspareunia and dysuria) Objective symptomatology (leucorrhoea, vulvar erythema, vulvar oedema and presence of abrasion/erosion) Vaginal PH PAP test. Patients will report their degree of satisfaction with h treatment using a 5‐point semiquantitative scale. Patients will be interviewed to monitor adherence to the study protocol and symptom trends during the 10‐day study period (groups A, B, C and D) and at 30 days (groups E, F) The safety and tolerability of the treatments will be assessed by reporting any local and anticipated adverse events

Nct (2022). "Efficacy and Safety of TQB2450 Injection Combined With Chemotherapy ± Anlotinib Hydrochloride Capsules for Advanced Endometrial Cancer or Sarcoma of Uterus." ClinicalTrails.gov.
	This study plans to enroll 69 subjects of endometrial cancer and 5‐10 subjects of sarcoma of uterus. The experimental set is divided into lead‐in trial and formal trial. The lead‐in trial includes 9 subjects to observe the safety of the combination and determine the dosage of anlotinib dihydrochloride capsules before the formal phase. The formal trial includes 60 subjects of endometrial cancer and 5‐10 subjects of sarcoma of uterus. The purpose is to evaluate efficacy and safety of TQB2450 injection combined with chemotherapy ± anlotinib hydrochloride capsules for first‐line treatment and maintenance treatment of patient with advanced endometrial cancer or sarcoma of uterus, and explore biomarkers related to efficacy, mechanism of action, safety and/or pathological mechanisms, the surgical conversion rate. ORR is the primary endpoint.

Nct (2022). "Efficacy of a Face to Face Versus a Remote Physiotherapy Instruction Session About Pelvic Floor in Women With Urinary Incontinence." ClinicalTrails.gov.
	The purpose of this study is to assess and to compare the efficacy of a face to face versus a remote physiotherapy instruction session about pelvic floor muscle (PFM) function, including teaching women how to contract their PFM and how to perceive a correct PFM contraction. Study participants will be randomly assigned to participate in one of the three study groups: Group 1 will receive face to face instructions, Group 2 will receive real time remote instructions and Group 3 will not receive any instruction. The primary outcome measure is PFM function assessed using the modified Oxford Scale.

Nct (2022). "Efficacy of Biofeedback-Assisted Pelvic Muscle Floor Training and Electrical Stimulation on Women With Stress Urinary Incontinence." ClinicalTrails.gov.
	Participant will be assigned randomly to biofeedback‐assisted pelvic floor muscle training (PFMT) group and biofeedback‐assisted pelvic floor muscle training (PFMT) combined with electrical stimulation group. Each of the participant will receive the therapy for two months.The investigators expected that combination therapy will improve the compliance and severity of symptoms in women with stress urinary incontinence.

Nct (2022). "Efficacy of Carbetocin Versus Oxytocin Plus Misoprostol in Decreasing Blood Loss During Cesarean Section." ClinicalTrails.gov.
	‐ Type of Study: A randomized controlled clinical trial. ‐ Study Setting: This study will be conducted in Ain Shams University Maternity Hospital (ASUMH). ‐ Study duration: 6 months. ‐ Study population: Women will be recruited from outpatient antenatal clinic of ASUMH. Sample Size: 104 patients will be enrolled in this study and will be divided into two groups: ‐ Group A: 52 patients will receive+ Oxytocin (20 IU IV infusion on 1000 ml of normal saline solution) plus misoprostol (600 micrograms rectal). ( The control group ) ‐ Group B: 52 patients will receive 100 micrograms Carbetocin IV slowly. Sample size justification By using PASS 11 software for sample size calculation, setting power at 80%, alpha error at 5% and after reviewing previous study results showed that the haemoglobin level (g/dl) postoperative to caesarean section was higher among women took Carbetocin than those took misoprostol (10.13 ± 0.76 versus 9.57 ± 0.95 respectively); based on that, a sample size of at least 90 pregnant females undergoing elective caesarean section divided randomly into 2 intervention groups [Carbetocin and misoprostol with oxytocin] (45 patients in each group) will be sufficient to achieve study objective, yet the drop out rate 17% so 7 patients will be added in each group. Procedures: 1. Approval of the protocol by the ethical committee of the department of Obstetrics & Gynecology, Faculty of Medicine, Ain Shams University. 2. Recruitment of patients planning to undergo elective cesarean section in ASUMH from antenatal clinic. 3. An informed written consent will be taken from all participants before enrollment in the study and after explaining the purpose, possible risks and complications. 4. All participants will be subjected to thorough history taking, general and abdominal examination, obstetric ultrasound examination and laboratory investigations including complete blood count to identify eligible patients. 5. The expert consultant will take the decision to do the cesarean section. 6. Eligible patients will be randomised & allocated into 2 groups (A) & (B). Randomization will be done using computer generated list. 7. Allocation & concealment will be done using sealed envelopes prepared according to computer generated list into ratio 1:1. Patients will deliver by cesarean section. Patients in group A will receive 600 micrograms misoprostol rectally immediately before sterilization plus 20 IU Oxytocin IV infusion on 1000 ml of normal saline solution immediately after delivery of the fetus. 8. Patients in group B will receive 100ug Carbetocin by slow IV infusion (over one minute) intra‐operative immediately after delivery of the fetus. 9. Estimation of blood loss will be calculated by : ‐ After delivery of the placenta, the amount of blood loss in the suction canister and drapes will be measured. ‐ The equation* used when calculating blood loss of a blood‐soaked item is WET Item Gram Weight ‐ DRY Item Gram Weight=Milliliters of Blood Within the Item. The items are weighed using a highly accurate digital balance ( Salter digital electronic scale 9037 TL3R). ‐ Although a gram is a unit of mass and a milliliter is a unit of volume, the conversion from one to the other is a simple 1‐to‐1 conversion. ‐ The amniotic fluid index (AFI) was estimated using abdominal ultrasound as the sum of the maximum vertical diameter of amniotic fluid in four quadrants in centimeters. ‐ Amniotic fluid volume (AFV) (ml) was estimated by multiplying AFI (cm) by 30. ‐ At the end of the surgery, the volume of quantified blood calculated by weight will be added to the volume of quantified blood in the suction canister then subtracting the amniotic fluid volume to determine total quantification of blood loss. 10. Follow up & data recording; • Post‐partum hemorrhage will be considered: 1. Minor PPH: if estimated blood loss from 500 ml to 1000 ml. 2. Major PPH: if any estimated blood loss is more than 1000 ml. ‐ Measuring hemoglobin level before & after 24 hours of delivery to asses the need for blood trans sion. ‐ All data will be recorded in Case Report Form.

Nct (2022). "Efficacy of Core Stabilization Exercises in Women With Stress and Mixed Urinary Incontinence." ClinicalTrails.gov.
	In our study, we aimed to evaluate the effects of core stabilization exercises added to traditional Kegel exercises on incontinence and quality of life in women with stress and stress dominant mixed urinary incontinence.

Nct (2022). "The Efficacy of Graminex® Flower Pollen Extracts in Healthy Women With Urinary Incontinence." ClinicalTrails.gov.
	The primary objective of this study is to investigate the effect of Graminex® Flower Pollen Extracts in healthy women with urinary incontinence. The change in severity of urinary incontinence between baseline and 24 weeks will be assessed by an International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), and compared between the investigational product and placebo groups. Additionally, the safety and tolerability of Graminex® Flower Pollen Extracts, as compared to placebo, will be measured by the occurrence of and/or changes in treatment‐emergent adverse events (AEs).

Nct (2022). "Efficacy of NAC for the Prevention and Relief of PIPN in Women With Ovarian, Tubal, and Peritoneal Cancer." ClinicalTrails.gov.
	This study was designed to evaluate the effect of NAC on the incidence and severity of PIPN in woman with ovarian, tubal, and peritoneal cancer who treated with paclitaxel for 3 cycles. (PIPPN is developed after cumulative doses 250 mg/m2 or more) Patient in controlled group, received Paclitaxel only. Patient in intervention group divided to two groups. First group received NAC 2400 mg/day for one week after received Paclitaxel each cycle for 3 cycles. Second group received NAC 2400 mg/day for 9 weeks Evaluate incidence and severity of PIPN before start CMT, and every visit after received CMT each cycle using Common Terminology Criteria for Adverse Event (CTCAE) ver.5, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group‐Neurotoxicity (FACT/GOG‐Ntx), and Patient Neurotoxicity Questionnaire (PNQ)

Nct (2022). "Efficacy of Neoadjuvant Hyperthermic Intraperitoneal Chemotherapy in Advanced High-grade Serous Ovarian Cancer (the NHIPEC Trial)." ClinicalTrails.gov.
	Background: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone. Methods: This study is a single‐centre, open‐label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60‐75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression‐free survival, overall survival and the rates of complete resection and NHIPEC‐related adverse events.

Nct (2022). "Efficacy of Primary Debulking Surgery Versus Neoadjuvant Chemotherapy in Stage IV Ovarian Cancer." ClinicalTrails.gov.
	Epithelial ovarian cancer (EOC) is one of the most common malignant tumors in women. Due to the insidious onset and the lack of effective early diagnosis measures, about 70% of patients with epithelial ovarian cancer are already in FIGO stage III‐IV at the time of diagnosis. With extensive tumor dissemination and metastasis, the 5‐year survival rate of EOC patients is only about 30‐40%. Currently, the standard treatment for ovarian cancer remains to include primary debulking surgery(PDS) and platinum‐based adjuvant chemotherapy. Despite the lack of evidence from prospective randomized controlled studies, evidence invariably shows that satisfactory debulking surgery improves survival prognosis in advanced ovarian cancer and that this benefit is significantly associated with the amount of residual lesion. How to increase the proportion of patients with satisfactory tumor reduction (residual lesions <1 cm) has long been a pressing issue for gynecologic oncologists. However, because ovarian cancer lesions are mainly disseminated in the pelvic cavity, the extent of surgery to achieve satisfactory reduction is often large and difficult to be tolerated for some patients. At the same time, due to the large initial tumor or the limited treatment level, some patients are unable to obtain satisfactory cytoreduction. Therefore, some scholars suggest that neoadjuvant chemotherapy (NACT) can be used to reduce the tumor load and control the patient's condition, followed by interval debulking surgery (IDS), called NACT‐IDS treatment model. Whether the NACT‐IDS treatment model can be used as a conventional alternative to PDS has been controversial. The foundation for NACT‐IDS was laid by two multicenter randomized controlled phase III clinical trials, EORTC 55971 and CHORUS. Both studies showed that the application of NACT in patients with advanced ovarian cancer resulted in a higher proportion of satisfactory cytoreduction and lower postoperative complications and mortality while ensuring a similar prognosis. However, the two studies mentioned above have been questioned by some scholars because of the lower median operative time, lower percentage of satisfactory cytoreduction, and lower patient prognosis than the international general level. Meanwhile, another phase III randomized controlled clinical trial, JCOG0602, was a non‐inferiority trial, and the results did not confirm that NACT was not inferior to PDS. Therefore, at present, NCCN guidelines recommend that PDS remains the first choice for most patients. At present, there are no relevant clinical trials comparing the impact of PDS with NACT on the prognosis of patients with ovarian cancer. In this study, investigators propose to assess the resectability of patients with abdominopelvic lesions using the Suidan standard resectability prediction model based on the evaluation of WB‐DWI/MRI. In patients of stage IV ovarian cancer with resectable abdominopelvic lesions, the prognostic impact of PDS and NACT will be compared prospectively and randomly, with the aim of providing a new decision basis for the treatment of patients with stage IV ovarian cancer.

Nct (2022). "Efficacy of the Vacucis Candida® Autovaccine." ClinicalTrails.gov.
	The design of a randomized, randomized (test and placebo) triple‐blind (patient, investigator and evaluator) clinical trial is proposed. The clinical trial will be carried out in accordance with the criteria recommended in the CONSORT Guidelines. All patients who agree to participate will have a sample taken following the manufacturer's instructions for the design of the autovaccine, using a sterile swab that will be placed in transport medium (AMIES type) and sent to the laboratory. After 1 month of taking the sample, the laboratory that will be in possession of the randomization will damage the container/dispenser, which will be exactly the same in both groups T and P. Group T will be administered the complete autovaccine, while group P , the content will be the same except for the active ingredient, that is, only thimerosal, methylcellulose, sodium chloride and orange essence. In this way, neither the research group nor the patient himself will be known by the group to which he has been assigned. In the event of unforeseen adverse effects, which are not expected, patients will be withdrawn from the study and treated according to standard care practice. All patients will be able to resort to rescue medication if the symptomatology is exacerbated during the follow‐up period of the study, always under the prescription of the physician (nystatin aqueous rinse solution 1ml/100,000 IU or oral Fluconazole 50 mg/24 hours).

Nct (2022). "The Efficacy of Therapeutic Exercises Delivered by Smartphone Application." ClinicalTrails.gov.
	Urinary incontinence (UI) is a common health disorder among women in Jordan and worldwide. UI affects women's quality of life, mental health symptoms, and social participation. However, limited numbers of women with UI seek help for their problems for many reasons, including lack of rehabilitation services, feelings of shame, and unwillingness to discuss their problems. Therapeutic exercise has been shown to be effective in UI management. However, there is a lack of physiotherapy services provided such necessary treatment. Moreover, mobile applications are becoming popular, and there are limited applications designed to help women with UI. Consequently, no study investigated the effect of a smartphone application with specific exercises program for UI management. Therefore, the aim of the study is to develop an evidence‐based therapeutic exercise application for UI and investigate its efficacy on UI clinical outcomes. We hypothesize that patients in the intervention group will have a significantly lower score of International Consultation on Incontinence Questionnaire‐Urinary Incontinence Short Form (ICIQ‐UI SF) , a lower score of perceived stress scale, lower Depression Anxiety and Stress scale (DASS‐21) score, a higher score of Multidimensional Scale of Perceived Social Support (MSPSS), a higher Short Form Health Survey (SF‐12) score, and a higher score of Incontinence Modular Questionnaire‐Lower Urinary Tract Symptoms Quality of Life (ICIQ‐LUTSqol) in comparison to the control group. A randomized controlled trial design. Sixty women with urinary incontinence will be included in this study. Participants will be randomized to the intervention group who will receive the mobile application (will include general information about UI and exercises) and the intervention group who will receive the sham application (include information about UI only). Outcome measures will include Arabic ICIQ‐UI SF to assess the frequency of urinary incontinence, the Arabic version of MSPSS to assess the social support, the Arabic version of (DASS‐21) to assess the mental health symptoms, SF‐12 to assess the quality of life, and ICIQ‐LUTSqol to assess the quality of life of women with UI.

Nct (2022). "Efficiency of Abdominal Corset and Core Stabilization Exercises in the Treatment of Postpartum Diastasis Recti Abdominis." ClinicalTrails.gov.
	30 volunteer women who were diagnosed with diastasis recti abdominis by an obstetrician in Çamlıca Medipol Hospital, aged between 18‐35 and met the inclusion criteria will be included in the study. Participants will be randomly divided into three groups. Participants in the first group will do core stabilization exercises for the transversus abdominis muscle 3 days a week for 8 weeks with 10 repetitions. In the second group, in addition to the first group, core stabilization exercises will be performed by wearing an abdominal corset. Participants included in the third group will be asked to wear only this corset all day (except for the bathroom) for 8 weeks. Anthropometric measurements, ultrasonographic evaluation, Visual Analogue Scale (VAS), Edinburgh Postnatal Depression Scale, abdominal muscle strength and endurance, Oswestry Disability Index will be evaluated as pretest and posttest.

Nct (2022). "EPOCH: eribulin and Pembrolizumab in Ovarian/Uterine Carcinosarcoma." ClinicalTrails.gov.
	EPOCH (Eribulin and Pembrolizumab in Tubo‐Ovarian and Uterine Carcinosarcoma) is an international clinical trial, which aims to improve outcomes in people with the rare and highly lethal Ovarian Carcinosarcoma (OCS) or Uterine Carcinosarcoma (UCS) malignancies. The underlying study rationale is based on robust preclinical evidence that demonstrated that eribulin, a microtubule inhibitor, can reprogram the tumour microenvironment, reversing epithelial mesenchymal transition (EMT) in these mesenchymal cancers, and potentiate the response to immune checkpoint blockade. In addition, expression of HMGA2, a high mobility group protein has been associated with activation of EMT process and may be a predictive biomarker of eribulin‐responsive cancers. This study is aimed at translating these laboratory findings to the clinic and treat patients with recurrent OCS and UCS with eribulin and the immune checkpoint inhibitor pembrolizumab, which targets and blocks the programmed cell death receptor 1 (PD‐1).

Nct (2022). "Evaluation of Metionac for the Modulation of Metabolic and Endocrine Parameters in Patients With PCOS." ClinicalTrails.gov.
	The investigators will explain the study to all patients who meet the inclusion and exclusion criteria during the study period. After signing the informed consent patients will be randomized 1:1 to oral contraceptive 4 mg drospirenone once daily or oral contraceptive 4 mg drospirenone + combination of 200 mg S‐adenosylmethionine, 100 mg N‐acetylcisteine, 75 mg Alpha lipoid acid and 0,65 mg vitamin B6 (Metionac) twice daily. Patients for whom oral contraceptive is not indicated will be enrolled in third study group of Metionac twice daily. 2 study visits will be carried out, Baseline (Visit 0) and after 6 months therapy (Visit 1).

Nct (2022). "Examining the Effect of Virtual Reality on Pain and Anxiety Management During Pelvic Examination." ClinicalTrails.gov.
	Objective: The study was conducted as a randomized controlled experimental study to examine the effect of the video watched with virtual reality glasses during the pelvic examination on the level of pain and anxiety perceived by women. Materials‐Methods: The sample of the study consisted of 128 women (64 experimental, 64 control group) who applied to the Obstetrics and Gynecology Polyclinics with non‐pregnancy complaints between November 2021 and February 2022, volunteered to participate in the study and were approved by the doctor for pelvic examination. Institutional and ethical committee permissions were obtained before starting the study. Descriptive Information Form, State Anxiety Scale, Visual Comparison Scale (GDS), Pelvic Examination Experience Evaluation Questionnaire, and Questionnaire Evaluating Non‐Verbal Responses to Emotional Stressful Situations, prepared by the researcher, were used to collect data. In the pre‐test to the women in the experimental group of the study: Descriptive Information Form, State Anxiety Scale, Visual Comparison Scale (for anxiety), then Pelvic examination + Virtual reality application (using virtual reality glasses for a minimum of 5 maximum 15 minutes), Emotional Stress to be applied by the researcher The Form Evaluating Non‐Verbal Responses to the Creating Situations, and in the post‐test: State Anxiety Scale, Visual Comparison Scale (anxiety + pain), Pelvic Examination Experience Evaluation Questionnaire were applied. In the pre‐test to the women in the control group of the study: Introductory Information Form, State Anxiety Scale, Visual Comparison Scale (for anxiety), then Pelvic examination (routine service), Form Evaluating Non‐Verbal Responses to Emotional Stressing Situations to be administered by the Researcher, In the post‐test: State Anxiety Scale, Visual Comparison Scale (anxiety + pain), Pelvic Examination Experience Evaluation Questionnaire were applied. Data were evaluated in computer environment and using SPSS 23.0 statistical package program. A p value of <.05 for the data was considered statistically significant.

Nct (2022). "Exercise and Pelvic Floor Health Education Program Effectiveness." ClinicalTrails.gov.
	3 group were created; the first group will applied Pelvic floor health education composed presentation about women health,urinary incontinence, teaching anatomy of the pelvic floor and bladder training ,second group will applied both pelvic floor health education and exercise of pelvic floor muscles for 12 weeks and third group will be control group.Women with urinary incontinence were included the study are continued 12 weeks . First evaluation is done before education and exercise program, and second evaluation in 6.week and last evaluation after 12 weeks exercise and education program.

Nct (2022). "Ferric Derisomaltose and Outcomes in the Recovery of Gynecologic Oncology: ERAS (Enhanced Recovery After Surgery)." ClinicalTrails.gov.
	Iron deficiency has been reported in approximately 35% of patients with a gynecologic malignancy. Blood transfusions are known to be immunosuppressive and carry immediate and long‐term risks. Pre‐operative blood transfusion in gynecologic oncology patients is associated with higher rates of surgical site infection, length of stay, composite morbidity, cancer recurrence, and mortality. Pre‐operative intravenous iron formulations have been shown in benign gynecology and other surgical specialities to increase pre‐operative hemoglobin and decrease post‐operative transfusion rates. This is a randomized double‐blinded clinical trial evaluating the effects of treating patients undergoing gynecologic oncology surgery with intravenous ferric derisomaltose to correct pre‐operative iron‐deficiency anemia. The study aims to assess the effectiveness of preoperative ferric derisomaltose/iron isomaltoside compared to placebo in correcting preoperative hemoglobin in patients undergoing surgery for gynecologic malignancy.

Nct (2022). "Ferric Derisomaltose/Iron Isomaltoside and Outcomes in the Recovery of Gynecologic Oncology ERAS." ClinicalTrails.gov.
	Iron deficiency has been reported in up to 35% of patients with a gynecologic malignancy. These patients often require surgical intervention to determine the stage and to treat their illness. Blood transfusions occur in approximately 14% of these surgeries and carry immediate and long‐term risks, including surgical site infection, cancer recurrence, and increased surgical length of stay. Intravenous iron formulations have the potential to rapidly correct anemia in patients with gynecologic malignancy and potentially decrease blood transfusion and complications following surgery. This prospective, randomized, placebo‐controlled, double blind study aims to assess the effectiveness of preoperative ferric derisomaltose/iron isomaltoside compared to placebo in correcting preoperative hemoglobin in patients undergoing surgery for gynecologic malignancy. The primary outcome is to assess the effectiveness of this formulation on pre‐operative hemoglobin, and the feasibility of a larger, outcomes based, study in the future. Exploratory outcomes are to assess the effect of preoperative intravenous iron on surgical length of stay, complications, and patient‐reported quality of life.

Nct (2022). "Fluzoparib and Apatinib Versus Fluzoparib in Relapsed Ovarian Carcinoma Maintenance Treatment." ClinicalTrails.gov.
	This study is a Phase II randomized, open label, controlled, multicenter study to access the effects and tolerability of fluzoparib combined with apatinib versus fluzoparib monotherapy for maintenance treatment in platinum‐sensitive relapsed ovarian carcinoma (including patients previous treated with a PARP inhibitor).

Nct (2022). "Gag Therapy for Recurrent Urinary Tract Infection Assessing Comparability to International Nitrofurantoin Gold Standard Study." ClinicalTrails.gov.
	The main objective of the study is to compare efficacy between hyaluronic acid ‐ chondroitin sulphate (HA‐CS) treatment and gold standard treatment (AB prophylaxis). Study is set‐up as non‐inferiority, parallel group trial, with a 1:1 randomization. Study population: Female (>18rs) with at least 3 symptomatic urinary tract infections (UTI's) in the previous year with no adequate curable therapeutic options. Intervention: Intervention group (n=50): 50ml of sterile Ialuril (HA 1.6% CS 2%) weekly for 6 weeks, followed by monthly maintenance therapy for 1 year. Control group (n=50): oral nitrofurantoin 100mg daily (1dd100mg or 2dd50mg) for 1 year. In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily will be given. During the study patients will fill‐out questionnaires regarding symptoms, quality of life and use of healthcare. Furthermore urine will be collected at set timepoints. Main study parameters/endpoints: The main study parameter is the number of UTI per patient‐year. Secondary parameters are time to rUTI (wks.), outcome on the global responce assessment (GRA) scale, pattern of antibiotic resistance, outcome on the patient reported outcome questionnaire, cost effectiveness and Quality‐of‐life.

Nct (2022). "Gemeprost Versus Dinoprostone in First Trimester Miscarriages." ClinicalTrails.gov.
	Women who are diagnosed with first trimester missed miscarriages are invited to participate in the study. They will be randomised to either gemeprost or dinoprostone.

Nct (2022). "GnRHa + Letrozole in Progestin-insensitive Endometrial Cancer and Atypical Hyperplasia Patients." ClinicalTrails.gov.
	There were more and more women with early endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (EAH) who want to preserve fertility. Approximately 70% to 80% of females who meet the criteria for conservation treatment are able to achieve CR after progestin therapy, with a median time of 6‐7 months, but about 20% to 30% of patients get no response or need to take longer time to achieve remission (over one year). With long duration of treatment, there will be more side effects such as weight gain, impaired liver function, endometrial injury, ovarian reserve inhibition etc. which will decrease the efficacy of conservative treatment. Previous researches had shown that GnRHa plus letrozole or ethinylestradiol cyproterone plus metformin could be a better second‐line treatment for progestin‐insensitive patients. Till now, no similar studies were found, so we design this study to explore the efficacy of GnRHa plus letrozole and ethinylestradiol cyproterone plus metformin in progestin‐insensitive EEC and EAH patients to provide new evidences for improving conservative treatment efficacy. Considered there will be more thrombotic risks in obese patients using ethinylestradiol cyproterone, we use GnRHa plus letrozole in patients with BMI ≥ 30kg/m2 only. This will be a single‐centred prospective pilot study. Patients diagnosed as progestin‐insensitive EAH or EEC by dilatation and curettage (D&C) or hysteroscopy will be enrolled. Non‐obese patients will be stratified by pathological diagnosis (EEC or EAH) and then they will be randomly assigned (1:1) to two arms. One will be GnRHa + letrozole group and another will be ethinylestradiol cyproterone + metformin group. And for obese patients,there will be only GnRHa + letrozole group. The primary endpoint is cumulative complete response (CR) rate at 28 weeks of treatment. The secondary endpoints include adverse events, duration of complete response, recurrent rate, pregnancy rate and quality of life of patients.

Nct (2022). "Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole In Young Women With Early Endometrial Cancer." ClinicalTrails.gov.
	This will be a multicenter randomized controlled study to evaluate the treatment effects and adverse events of GnRHa plus AIs compared with MA/MPA in primary EEC patients.In this study, young patients (18‐45 years) diagnosed as EEC for the first time seeking for fertility preserving treatment at the Obstetrics and Gynecology Hospital of Fudan University were screened. Patients were randomly assigned (1:1) to GnRHa+letrozole group (triprorelin acetate, intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses. letrozole, 2.5mg oral daily and no more than 24 weeks) or MA/MPA group (160 mg oral MA daily or 500 mg oral MPA daily). Hysteroscopy will be performed every 3 months during treatment to evaluate the treatment effects. For patients with EEC, complete response (CR) is defined as the reversion of endometrial carcinoma to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia with or without atypia; Stable disease (SD) is defined as the persistence of the disease; and progressive disease (PD) is defined as the progression of endometrial lesions. Continuous therapies will be needed in PR, SD or PD.The primary endpoint was cumulative complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were cumulative CR rate at 28weeks of treatment, adverse events, recurrent rate, pregnancy rate, effects on ovarian function and quality of life of patients.

Nct (2022). "Guideline-directed Management and Therapy (GDMT) for the Prevention of Postpartum Cardiac Dysfunction in Preeclamptic African American Women." ClinicalTrails.gov.
	This study is looking at when given GDMP in post‐partum women with preeclampsia, compared to the current standard of care, can this therapy improve Global Longitudinal Strain (GLS) at 9 months. Subjects who agree to participate and who have already completed the PARENT study (NCT04479072) at 6‐months will be randomized in this study to either the GDMP (Treatment) arm or the standard of care (Observational) arm. Subjects that agree to participate in the extension part of the study, will add on an additional 3 months. The primary objective of this study is to mechanistically determine the effect of GDMT administered at six months postpartum on GLS at nine months postpartum in African‐ American patients at high risk due to elevated blood pressures (>120/80 mmHg). The trial biostatistician will create the randomization schedules using computer‐generated random numbers and will have access to treatment group allocation. Below are further details on each arm. Treatment Arm: Subjects randomized into the treatment arm will be enrolled into the remote patient monitoring program (RPM). Subjects who enroll in the sub‐study will utilize the RPM by the University of Chicago Heart Failure Program. This program enables providers to track the number of critical vitals in real time. Patients are equipped and trained to monitor blood pressure, heart rate, weight, temperature, and medication adherence, through a Bluetooth‐enabled tablet that integrates and transmits data to the clinic providers and advanced practitioners. This system is currently in use by the heart failure program at the University of Chicago, including hospital‐to‐home transition care after hospitalization for decompensated heart failure and long‐term outpatient management of chronic heart failure, hypertension, atrial fibrillation, and ischemic heart disease. The heart failure team will provide the tablet, blood pressure cuff, weight scale and training at the subjects baseline visit. Observational Arm: Subjects randomized to this arm will receive the standard of care based upon the American Heart Association (AHA) and American Congress of Obstetricians and Gynecologists (ACOG) guidelines, which include counseling of increased cardiovascular risk, lifestyle modifications, including a healthy diet, exercise, smoking cessation, and risk factor intervention as determined by the primary care physician. They will not be receiving the RPM program equipment. Follow‐up clinic visit approximately 3 months after they have been randomized will be scheduled in both arms. At this visit the study team will; Perform a Transthoracic echocardiogram (TTE) Obtain Vital signs Physical Exam Adverse Event check Concomitant Medication check Blood draw for laboratory test In addition, the study team will conduct monthly telephone interviews of all randomized trial participant's for concomitant medications, adverse events/side effects, and study drug compliance.

Nct (2022). "Half Swaddle and Kangaroo Care in Preterm on Breastfeeding, Infant Attachment, Sleep Quality and Depression of Mothers." ClinicalTrails.gov.
	The prospective, randomized controlled study was conducted on 160 mothers with premature babies whose age were between 18 and 49 randomly divided into four groups as 40 case group, 40 half swaddle group, 40 kangaroo care group, 40 half swaddle and kangaroo care group at the neonatal intensive care service and birth service of Trakya University Health Research and Application Center between September 2020 and March 2022. In order to determine the number of samples, in order to test the difference in the effect size of 0.3326851 calculated between the groups based on the 1‐month difference in the EPDS scores in the study of Herizchi et al. (2017), with 5% margin of error and 95% power, a total of n=40 from each group was used. It was calculated that the mothers who gave =160 preterm births should be included in the study. N=160 samples of preterm infants were randomized with the help of ASS 11 (NCSS, LLC. Kaysville, Utah. www.ncss.com) computer program, HS group (n=40), KC group (n=40), HS+KC group. (n=40) and control (n=40) groups. Data were collected using Survey Form, Edinburgh Postpartum Depression Scale (EPDS), Pittsburgh Sleep Quality Index (PSQI), Mother‐to‐Infant Bonding Scale (MIBS), Breastfeeding Self‐Efficacy Scale‐Short Form (BSES‐SF), Latch Breastfeeding Diagnosis Measurement Form, Perception of Insufficient Milk Questionnaire (PIMQ). Data were evaluated using descriptive analyses, Mann Whitney U, Kruskal Wallis Test, Friedman S Test, Spearmen Correlation, multiple linear regression analysis. Research data It was collected using the Survey Form, Edinburgh Postpartum Depression Scale (EPDS), Pittsburgh Sleep Quality Index (PSQI), Mother‐to‐Infant Bonding Scale (MIBS), Breastfeeding Self‐Efficacy Scale‐Short Form (BSES‐SF), Latch Breastfeeding Diagnosis Measurement Form, Perception of Insufficient Milk Questionnaire (PIMQ). Survey form; It which was prepared by the researchers by reviewing the literature consists of 5 main sections and a total of 82 questions, including the personal characteristics of the mother who gave birth preterm, the characteristics of the birth and the baby, the characteristics of sleep, the characteristics of the baby's sleep pattern, and the characteristics of the baby's growth and development. Edinburgh Postnatal Depression Scale (EPDS): The scale was developed by Cox and Holden (1987). Adapted to Turkish by Engindeniz, Küey, and Kültür (1996). It is used to determine the risk for depression in the postnatal period and to measure the level and change of violence. It is a self‐assessment scale. It is applied to postpartum women. It contains a total of 10 questions and measures depression. It provides a four‐point Likert type measurement. The directive is at the beginning of the scale and subjects are asked to mark the substance most relevant to their situation when filling in the subjects. The total score of the scale is obtained by adding these item scores. As a result of the cut‐off point scale study conducted in Turkey and it has ben calculated as 12/13 Pittsburgh Sleep Quality Index (PSQI): PSQI is a self‐reported screening and assessment questionnaire that details information on the type and severity of sleep quality and disorders within the last month. It was developed by Buysse et al. (20), and its validity and reliability study in Turkish was performed by Agargün et al. (21). PUKI evaluates sleep quality in the last month. 18 items and 7 components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping pills, daytime dysfunction) are included in the scoring. Each item is evaluated over 0‐3 points and the sum of 7 component points gives the total PUKI score. The total score ranges from 0 to 21, with higher scores indicating worsening sleep quality. A total PUKI score of ≤5 is considered "good sleep", and >5 is considered "bad sleep". Mother‐to‐Infant Bonding Scale (MIBS): MIBS was developed by Taylor et al.12. The MIBS is a measurement tool that can be applied easily n quickly by the puerperal from the first day of the postpartum period and that allows the mother to express her feelings for her baby. This scale shows the relationship between the bond between mother and infant and the mother's mood during the early postpartum period. The MIBS is a four‐point Likert‐type scale consisting of eight items. Answers are scored between 0‐3, the lowest score that can be obtained from the scale is 0 and the highest score is 24. High scores indicate a problem with mother‐infant bonding. A Turkish validity and reliability study of the scale was conducted by Karakulak and Alparslan. Breastfeeding Self‐Efficacy Scale‐Short Form (BSES‐SF): The BSES‐SF was developed by Dennis (1999). Later, the short form of the scale was developed by Dennis (2003) by reducing it. The BSES‐SF is a 14‐item instrument developed to measure breastfeeding confidence. All the items are preceded by the statement "I can always" and are anchored by a five‐point Likert‐type scale, with 1 = not at all confident and 5 = always confident. All the items are presented positively and the scores are summed up to produce a final score ranging from 14 to 70, with the higher scores indicating better BSE. Turkish validity and reliability of the scale were done by Tokat and Okumuş (2013). Latch Breastfeeding Diagnosis Measurement Form: It is a measurement tool developed by Jensen et al. (1994). The Turkish validity of the Latch Breastfeeding Diagnosis Measurement Form was performed by Yenal and Okumus (2003). The Latch Breastfeeding Diagnosis Measurement Form consists of the combination of the first letters of the English equivalent of the five evaluation criteria and is listed as follows: L (Latch on breast), A (Audible swallowing), T (Type of nipple), C (Comfort breast/nipple), H (Hold / Help). Each item in the scale is evaluated between 0‐2 points. The lowest 0 and the highest 10 points are obtained from the scale. Total high score indicates the baby's sucking success. Perception of Insufficient Milk Questionnaire (PIMQ): Designed based on the conceptual model of McCarter‐Spaulding and Kearney (2001), clinical experience, and literature, this six‐question questionnaire was designed to measure the perception of insufficient milk in breastfeeding mothers. Turkish validity and reliability study was done by Gökçeoğlu. The first question is a ''yes'' or ''no'' question about whether them other perceives her milk as sufficient and other questions assess whether the mother perceives her milk as insufficient. Mothers rated these questions between 0 and 10, with ''0" meaning that her milk is perceived as completely insufficient, and ''10" meaning that her milk is perceived as completely sufficient. The lowest and highest scores possible on the scale are 0 and 50, respectively. The value of the total score indicates how high the score is and whether the perception of the amount of milk is sufficient. Data collection The mean scores of BSES‐SF, IMPS, LATCH, MIAS, PSQI and EPDS at the beginning, 1st, 2nd, 3rd and 6th months of the half swaddling and kangaroo care group Intervention. Half swaddle: HS applied to a newborn baby makes the baby feel completely safe, as if in the womb. After laying the soft fabric or baby blanket, it was placed in the supine position. Half swaddling was done so as not to restrict the baby's arm and leg movements. HS was performed 15 minutes before each sleep during the day until the 3rd month. Kangaroo care: The application was applied at twice a day and for 60 min, every day for 6 months in a row. While the mothers were taken to the NICU and practiced at home prior to kangaroo care, hand hygiene and breast care were provided within the scope of infection prevention rules. During KC, the mother placed her baby between two breasts, and the baby's breast was placed on the mother's breast in an upright position. During the application of KC, a quiet, calm and suitable environment was created so that comfort of the baby and mother would not be disturbed. The mother and baby are covered it a blanket. The ambient temperature was 26 centigrade degrees during the kangaroo care. In the continuation of the KB application, the mother was asked to breastfeed her baby. In order to prevent the risk of aspiration of the baby after breastfeeding, the baby was placed in the left lateral position so that the mother and the baby could lie down together. The application steps of the mother's KC were observed by the researcher and the deficiencies, if any, were corrected by discussing with the mother during / after the application. Control group: The mothers in the control group were given routine care.

Nct (2022). "Hand Driven Versus Motor Driven Hysteroscopic Tissue Removal System for Polypectomy: long-term Results." ClinicalTrails.gov.
	‐ Rationale: several techniques for hysteroscopic removal of intrauterine polyps exist today. Hysteroscopic morcellation is an effective, fast, and safe method for this. However, the differences between two different systems of hysteroscopic morcellation, motor‐driven (Truclear incisor mini device) and hand‐driven (Resectr 9fr) morcellation, are still unclear. The REMOvE9 study, in which women with a polyp were randomized between both techniques, is currently investigating the differences in short‐term effectiveness between the two techniques. ‐ Research question/goal: To investigate the long‐term results of the effectiveness of a hysteroscopic morcellation of intrauterine polyps. The two systems are compared with each other. ‐ Study design: This is a prospective cohort study. The patients previously participated in a randomized controlled trial (REMOvE9) and will now be contacted again for the completion of a one‐time questionnaire. The study has an observational design. ‐ Study population: Women with a history of endometrial polyp that was previously removed via hysteroscopic morcellation in the REMOvE9 study. ‐ Primary and secondary endpoints: The primary endpoint is the risk of recurrence of abnormal uterine bleeding at post‐surgery follow‐up. Secondary endpoints include recurrence of other symptoms, time to recurrence, symptom relief, onset of new symptoms, onset of new polyp, satisfaction with regards to symptoms, satisfaction with regards to the treatment in general, need for additional treatments for blood loss and occurrence of pregnancy (in subfertility group).

Nct (2022). "Hericium Erinaceus Mycelium and Probiotic of the Grape King Bio on Symptoms of Premenstrual Syndrome." ClinicalTrails.gov.
	This study was a randomized, double‐blinded and placebo‐controlled research. This study was approved by the Institutional Review Board of the Chung Shan Medical University Hospital and all Participants signed the written informed consent to participate in the study. Participants met the inclusion criteria, ie: age 20 45 yr and a regular menstrual cycle (21 35 days per cycle) were recruited through advertisements posted around the Chun Shan Medical university campus. In screening phase of this study, affective and one somatic symptom in before onset of menstruation in two consecutive cycles and was not affected by depression or anxiety disorder, she is examined by the Attending Physician of the Obstetrics and Gynecology Department to diagnosed a patient with premenstrual syndrome. In the intervention phase of this study, 105 eligible participant were randomly divided into intervention (Grape King Hericium erinaceus Mycelium Capsules and Grape King Probiotic Capsules) and control groups (n=35/group). Both subjects and researchers were blind to the treatment assignment until the statistical analysis was completed. All participants received two oral capsules containing Hericium erinaceus Mycelium, probiotics or placebo every day for the 3 months. The capsules of intervention supplementations and placebo provided by Grape King Biotechnology Inc in identical appearance and package to guarantee the blindness. Data collection A validated semi‐quantitative Food Frequency Questionnaire was used to obtain daily nutritional values of participants. To assess the symptoms of PMS, all subjects need to fill out daily record of severity of problems on a daily basis in the 3 months of intervention period and 6 months after the intervention. In the 0, 1, 3 months of intervention, the anthropometric parameters and body composition were measured by using bioelectrical impedance analysis method ( MC‐980 MA PLUS, TANITA BIA Technology). In the 0, 1, 3 months of intervention, venous blood samples were taken from all subjects for measuring the marks of oxidative stress and inflammation.

Nct (2022). "High Intensity Resistance and Aerobic Training Among Women With PCOS." ClinicalTrails.gov.
	PCOS is a prevalent condition that is affecting adolescent girls now and has serious impacts on menstrual health and quality of life making them prone to early risk development for chronic metabolic diseases. The comparison between high intensity resistance and aerobic training would give results that which one is more effective in gaining benefits and better effects on overall health both physically(menstrual) as well as mentally that would eventually tell us about the quality of life of such patients. After the initial screening process, the participants fulfilling the Roterdam criteria, willing to participate in the exercise trial will be recruited and then randomized to the allocated groups of either high intensity resistance or high intensity aerobics. At baseline, their anthropometrics measurements, LH/FSH ratios and fasting plasma glucose test will be done. Patient will be called thrice a week for 3 months for training. It is hypothesized that high intensity resistance or high intensity aerobics will improve anthropometric measures along with hormonal profile and quality of life.

Nct (2022). "Hybrid Versus Synthetic TOT for Treatment of SUI." ClinicalTrails.gov.
	The present study will be a single center randomized clinical trial. Recruitment will be performed among women presented to Alexandria Main University Hospital urology clinic complaining of urinary stress incontinence, in whom surgery was regarded as the treatment of choice. Women will be eligible if they have a positive stress test. The stress test will be performed in a semi lithotomy position with a semi full bladder. Women will be randomized into the groups by using Sealed Opaque Envelope System. Patients will be randomized into 2 groups of 25 patient each. One group will be subjected to hybrid TOT, and the second to conventional TOT. Preoperative and post‐operative (at 3 and 6 months) will include: ‐ Clinical examination including cough stress test. ‐ Patient global impression questionnaire (PGI) ‐ Patient questionnaire for incontinence (UDI‐6) ‐ Urodynamic (pressure‐flow study) No concomitant surgery will be performed on women enrolled in the trial. All patients will give a written informed consent. Technique of hybrid TOT The procedure will be performed while the patient is in dorsal lithotomy position under spinal saddle anesthesia. A sterile 14 Fr. Foley catheter will be placed per urethra to empty the bladder. The next step will be to harvest a strip of rectus fascia. A 4‐5 cm transverse abdominal incision will be made 2 cm cephalad to the pubic symphysis. Anterior rectus fascia will be exposed and an approximately 8‐10 cm × 1 cm strip of rectus fascia will be marked out. The sling will be harvested using sharp dissection and the anterior rectus fascia defect will be reapproximated using 1‐0 Prolene suture. Thereafter, a Polyprolene monofilamentous mesh of 15 cm x 1 cm will be sutured to each edge of the rectus fascia sling that had been harvested. Then, normal saline will be injected in the space between the anterior vaginal wall and mid urethra for hydrodissection, followed by a 2‐cm midline incision over the anterior vaginal wall at the level of mid‐urethra. A combination of blunt and sharp dissection will be carried out to the obturator foramen bilaterally. Next, a stab incision will be made at a point approximately 2.5 cm infero‐lateral to the pubic tubercle bilaterally, corresponding to the level of clitoris. A trocar (C‐shaped, specially built for the TOT) will be passed through each obturator foramen (outside‐in) and the edge of the mesh will be retracted through the incision. The same process will be repeated on the other side. Next, the retraction of both meshes will continue until the rectus fascia sling remain flushed with the urethra. An artery forceps will be kept between the fascia and the urethra to avoid excessive tension. Excess mesh on each side will be removed. The sling will be secured to the peri‐urethral tissue with interrupted polyglactin 4‐0 suture to prevent rolling and to ensure a flat, broad based sling. The stab incisions will be closed. The anterior vaginal wall will be closed with polyglactin 4‐0 suture. Vagina will be packed with povidone iodine‐soaked gauze. Vaginal pack and urethral catheter will be removed in the morning of the first postoperative day. The 2 groups will be compared using the standard statistical methods regarding outcomes and complications. The primary outcome of the study will be achievement of continence (efficacy) while the secondary outcomes will include intraoperative and early post‐operative complications, convalescence, and quality of life.

Nct (2022). "Hyperthermic Intraperitoneal Chemotherapy With Cisplatin During Surgery or Cisplatin Before Surgery for the Treatment of Stage III or IV Ovarian, Fallopian Tube or Peritoneal Cancer." ClinicalTrails.gov.
	PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of intravenous (IV) cisplatin on the day prior to interval cytoreductive surgery (CRS) to administration of hyperthermic intraepithelial chemotherapy (HIPEC) with cisplatin at the completion of CRS versus standard chemotherapy and interval surgery. SECONDARY OBJECTIVES: I. Feasibility of each of the treatment options. II. Treatment delays. III. Perioperative outcomes. IV. Quality of life/patient reported outcomes. V. Recurrence free survival (RFS) and overall survival (OS). OUTLINE: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3‐4 cycles in the absence of disease progression or unacceptable toxicity. Within 3‐4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval debulking surgery Patients are randomized to 1 of 3 arms. ARM I: No chemotherapy immediately before, during or after surgery. Carboplatin/paclitaxel is given 3‐4 weeks prior to surgery and again 2‐4 weeks after surgery. ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of interval debulking surgery ARM III: Patients receive cisplatin IV the day prior to interval debulking surgery After completion of study treatment, patients are followed up for up to 30 days.

Nct (2022). "Hypopressive Exercise Associated With Strength and Resistance Training in Women Treated for Gynecological Cancer." ClinicalTrails.gov.
	Objective: To evaluate the effects of 4 weeks of hypopressive exercise associated with resistance training and aerobic exercises on fatigue, symptoms of urinary incontinence, sexual function and quality of life in women treated for gynecological cancer compared to a group that will perform conventional training. Methods: This will be a single‐blind randomized clinical trial. A hypopressive exercise intervention associated with resistance training and aerobic exercise will be carried out during twelve telerehabilitation sessions. Patients over 18 years of age who are diagnosed with gynecological cancer and who are indicated for radiotherapy or chemotherapy will participate. Patients will be randomly assigned to an experimental group of hypopressive exercises associated with resistance training and aerobic exercises or conventional training. Fatigue, quality of life, symptoms of urinary incontinence and sexual function will be evaluated before and after the intervention. Discussion: The results of this clinical trial will determine the impact of conventional training associated with hypopressive exercise on the negative side effects of cancer treatment in women with gynecological cancer.

Nct (2022). "Hysteroscopic Isthmocele Repair on IVF Outcome." ClinicalTrails.gov.
	Hysteroscopic Isthmocele repair on IVF outcome Background: Uterine niche is a very common finding in women with previous caesarean section. Subfertility can be associated finding and IVF outcome can be affected by its presence. It is not yet if its treatment before IVF trial could improve the outcome of IVF cycle. Objectives: assesse the efficacy of Hysteroscopic CS scar defect repair on the clinical pregnancy rate after embryo transfer. Methods This prospective randomized controled will be conducted at Healthplus fertility center. The population of the study will be Patients who was diagnosed with significant caesarean section scar defect and had a previous unsuccessful ongoing pregnancy after embryo transfer of one or more euploid embryo and planning for another trial of one euploid embryo transfer. Twenty five of them will be be randomized to hysteroscopic repair before having embryo transfer. and 25 will go directly for embryo transfer. Clinical pregnancy rate is the primary outcome. Seconday outcomes are Complications following hysteroscopic CS scar repair, the need of aspiration of intrauterine fluid before embryo transfer, early pregnancy complications, Caesarean section scar dehiscence or rupture and live birth rate.

Nct (2022). "Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis." ClinicalTrails.gov.
	This study will treat subjects with complicated VVC who have failed prior fluconazole therapy with Ibrexafungerp for 1, 3 or 7 days of treatment. Approximately 150 eligible subjects will be enrolled. Subjects will be randomized to receive oral ibrexafungerp 300 mg administered twice a day (BID) for either one, three, or seven consecutive days, stratified by group based on Candida species and presence or absence of underlying medical conditions. The primary endpoint for this study is the percentage of subjects with a clinical cure at the Test of Cure Visit. Test of Cure is defined as a score of zero on the Vulvovaginal Signs and Symptoms Scale and not requiring additional antifungal treatment.

Nct (2022). "Ideal Timing of Intrauterine Contraception Insertion After Medical Management of First Trimester Incomplete Abortion." ClinicalTrails.gov.
	Rationale for study: Early IUC insertions post first trimester medical abortion management avails the opportunity of utilizing the limited human resource in low resource setting. Prior studies have shown higher continuation rates and patient satisfaction with early IUC than with the standard insertion between 2‐4 weeks after medical PAC. There's also no need for back up contraception with early IUC as implemented for standard IUC. Objective: To compare the expulsion rates and continuation rates at six months between early IUC and standard IUD insertions among women managed with mPAC after first trimester incomplete abortion. Null hypothesis: Early Insertion of IUC has higher expulsion and continued use rates than standard insertion after medical management among women with first trimester incomplete abortion at six months within a non‐inferiority margin of 7.5%. Alternate hypothesis: Early Insertion of IUC has similar expulsion and continued use rates as standard insertion after medical management among women with first trimester incomplete abortion at six months within a non‐inferiority margin of 7.5%. Sample size and calculated power: With an assumed 95% "success" (non‐expelled IUDs) in both groups with a power of 90 percent and an alpha of 0.05 the investigators would need to randomize 905 women in each group. Calculating for sample size for cluster randomized sampling, In a meta‐analysis by Adams, the median ICC was observed at 0.005. Considering the sample size calculation of 1770, For 15 clusters (units), average cluster size = 1770/15 = 118 Applying the formula, the investigators get DE = 1.585 Overall sample size = 1770 * 1.585 = 1805 Adjusting for a 15% loss to follow up gives a total sample size of 2076 Sample size estimation for the Continuation rates at 6 months: Shimoni reported six months' utilization at 69% and 60% for the early and standard insertions respectively. Based on a non‐inferiority margin of 7.5%, a sample size of 497 is needed. For 15 clusters (units), average cluster size = 994/15 = 66 Applying the formula, DE = 1.585 Overall sample size = 994 * 1.585 = 1575 Choosing the bigger sample size and 15 percent loss to follow up which is commonly seen in studies on abortion. Thus, investigators will randomize 2,076 women. Randomization: The randomization sequence will be generated using STATA 12 software package in a ratio of 1:1 allocation using permuted block size of 4, which will be varied randomly. The randomization will be performed by the Bio‐statistician who will remain with the randomization list. This process will be accomplished before the study starts. The investigators and research assistants will not access the randomization list. Allocation concealment: Sequentially numbered, identical, opaque, sealed envelopes prepared by staff otherwise not involved in the trial to conceal the pre‐specified intrauterine contraception allocation from clinicians, research personnel, and participants will be used. After screening, women who will be eligible for IUC will be randomized to receive early or standard insertion of IUC by a different team from the one that ensured allocation. Blinding: The study will be an open label design. Choice of Study Design: The study will be a non‐inferiority trial. Enrolment: All women with incomplete first trimester abortions managed medically with Misoprostol will be invited to be included in the study at the initial outpatient consultation. The women will receive detailed oral and written information regarding the study. An informed consent will be signed by the attending physician and the woman before randomization and any other study related activity. Allocation and treatment: Designated study nurses and doctors will be responsible for recruiting and examining study participants at the outpatient clinic. Eligible women will then be randomized into either: Group 1; early insertion or Group 2; standard insertion. Women will be free to decide between the Cu‐IUD (Nova T, Bayer AG, Berlin, Germany) and the LNG‐IUS (Mirena H, Bayer AG, Berli Germany). Medical PAC will be performed according to the evidence based guidelines. Women with first trimester incomplete abortion diagnosed on history taking and clinical examination will be given Misoprostol 400 mcg sublingually as a single dose. Prior to this, two Ibuprofen 200 mg tablets every 8 hours for three days and two Paracetamol 500mg tablets will be taken orally for three days. Additional analgesia will be available whenever needed. As prophylaxis against post abortion endometritis, two Metronidazole 200mg tablets taken orally every 8 hours for five days and one Doxycycline 100mg tablet twice daily for five days will be given to all participants. Procedure: The woman will be in supine position with her legs in stirrups. A speculum will be inserted into the vagina and a tenaculum placed on the cervix to straighten the uterus. A sound will be inserted when thought appropriate into the uterus to measure the length to the fundus and thereafter the IUC will be placed at the fundus of the uterus. Threads will be cut at 3 centimeters length. Follow up: All participants will be followed up for at least one year. Follow up visits will be scheduled at two weeks, three, six and twelve months of IUC insertion. At each scheduled visit, the participants will undertake standardized history and physical examination. If a participant misses a scheduled visit by two weeks she will be contacted by phone, reminded of the missed visit and rescheduling of her appointment done. Home visits will be made for participants who will be lost to follow up. At every visit, the women will be assessed clinically for possible development of PID. They will be asked about development of complications and whether they received any medication from other sources. Information about IUD removal, IUD expulsion, heavy or prolonged menstrual bleeding or missed menstrual periods and hormonal side effects related to progesterone will be ascertained. Women will be requested to keep notes on the menstrual changes on all follow up visits. Analysis plan: Independent variables between the Early vs. Standard insertion groups will be assessed to determine whether they are similar. The database will contain information on demographic variables that will be analyzed by Mann Whitney U‐test. Expulsion as a function of time will be analyzed using Cox regression analysis and visualized by Kaplan Meier curves. In addition multivariate regressions that explore influence of parameters on outcome measures and interactions between various covariates and primary and secondary outcomes will be performed using logistic regression analysis for dichotomous parameters and after dichotomization of continuous parameters. An intention to treat analysis as well as per protocol analysis will be performed. Participant Retention in the study: The research team will ensure that the participants are comprehensively informed of the follow up schedule. A phone call and text message will always be used to remind the participants at least 72 hours prior to their scheduled visits. Transport reimbursements will be given to all study participants at every follow up visit. A readily available contact of a study nurse will be offered to all participants over 24 hours every week to address any issues that they will have with the study intervention or process. A participant will be regarded as loss to follow up if they fail to honor their appointments after one month of every attempt to have them come back fails. Data security: All databases will be accessed only by the personnel directly involved in the study. The consents and the questionnaires will be kept separately in a lockable research office. Study participants will not be identified by name in the final report. Data Monitoring: A multidisciplinary committee comprising of a pharmacist, gynecologist, social worker and one member of the IRB will form the Data Safety and Monitoring Board (DSMB). This committee will report to the steering committee which will comprise of the Doctoral committee. To avoid conflict of interest, the DSMB will a e no funders or any of the members involved in the implementation of the research. They will have access to the study findings and will report to the steering committee, interim analysis results with recommendations on whether to halt or continue with the study. Trial Auditing: A committee of experts in the study to oversee the data control process will be constituted. This committee will work with monitors, trial coordinators and investigators. The monitors will also work with the coordinators to ensure that all the required documents like IRB clearance and correspondence forms, case report forms, patient consent forms, study agreements, adverse events forms, study protocols, institution clearance forms and all source documents like patient charts are filed in a binder that can easily be retrieved whenever needed. The monitors will notify the teams at least a fortnight prior to their visit to ensure timely preparations. Modifications in the Protocol: In cases of any amendments in the study objectives, major administrative changes, sample size, potential benefits or safety concerns, the IRBs will be notified by the study Principal Investigator. Minor amendments like changes in the administration that don't affect the running of the study will also be communicated at the discretion of the steering committee as a memorandum to the IRBs. Confidentiality: All study related information will be kept secure at the study sites. Patient files and records will be kept in lockable cabins with limited access. Only the steering committee and DSMB will have full access to the information. Patient identifiers will never be kept with the study findings to ensure confidentiality in the study. Stopping rules: An interim analysis of results will be performed when 50 percent of women have been recruited. If expulsion rates exceed 20 percent, the study will be stopped. As recommended by Korn, when the Hazard ratio equals or exceeds the preselected non‐inferiority margin for our study of 7.5% at 50 percent recruitment, DSMB will stop the study. Adverse Events: Any untoward medical occurrence without regard to the possible causality in a study participant, in our study will be defined as an adverse event. All adverse events will be recorded from the point the participants sign the consent forms to discharge from the hospital. All serious adverse events will be reported within seven working days to the IRB. Within 24 hours of occurrence of the adverse events, the investigators will set out to establish the relation of the events whether unexplained or unexpected based on the documentation in the consent process or protocol and post abortion intrauterine devices. Uterine perforation, need for exploratory laparotomy after post abortion intrauterine device insertions, need for blood transfusion following severe hemorrhage, hospitalization over 72 hours, anaphylactic reaction after IUD insertion, life threatening sepsis, or deaths will be regarded as severe adverse events. Participants with adverse events will be managed immediately by the care teams at the different facilities as per the standard operating procedures. Quality control: The Principal Investigator will carry out a trial run for a month to pre‐test all study instruments, streamline the process of enrolment, allocation and follow up at the health facilities prior to starting data collection. All research assistants involved in the study will undergo training on research conduct prior to the study. A coordination team will be set up to supervise the study and offer support. All filled or recorded data will be checked on a daily basis for completeness. A Data safety monitoring board will be formed to monitor patient safety during the implementation of the RCT.

Nct (2022). "Impact of Basic Needs Assessment and Support to Improve Colposcopy Show Rate." ClinicalTrails.gov.
	The investigators will perform a randomized controlled trial in which 72 eligible patients (low‐income, uninsured, or on Medicaid) who are referred for colposcopy at Washington University School of Medicine, are enrolled and then screened for unmet social needs and distress. The participants will then be randomized 1:1 into either receive the social needs navigator program (n=36) or enhanced usual care (n=36).

Nct (2022). "Impact of Sentinel Lymph Node Mapping on Patient Reported Lower Extremity Limb Dysfunction in Stage I Endometrial Cancer." ClinicalTrails.gov.
	PRIMARY OBJECTIVES: I. To compare the rates of lower extremity limb dysfunction (defined as a >= 4‐point increase in Gynecologic Cancer Lymphedema Questionnaire [GCLQ] symptom score from baseline) in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy: Ia. Sentinel lymph node mapping followed by side‐specific lymphadenectomy on sides without a sentinel lymph node (SLN) identified according to a National Comprehensive Cancer Network (NCCN) guidelines approved algorithm (Arm 1); Ib. Sentinel lymph node mapping according to an NCCN Guidelines approved algorithm followed by bilateral pelvic +/‐ para‐aortic lymphadenectomy (Arm 2). SECONDARY OBJECTIVE: I. To compare changes in lower extremity limb circumference in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy. II. To validate the test characteristics of a SLN mapping algorithm including SLN detection rates, rate of perioperative complications, rate of identifying lymphatic metastases, and detection of micrometastases using pathologic ultra‐staging. EXPLORATORY OBJECTIVES: I. To compare adjuvant therapy decisions in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy. II. To explore the impact of patient characteristics (age, body mass index [BMI], race), extent of lymph node dissection, and adjuvant therapy decisions (radiation, chemotherapy) on the development of lower extremity limb dysfunction ‐ as well as their interaction with lymph node assessment strategies. III. To evaluate the cost‐effectiveness of SLN mapping with or without completion of lymphadenectomy for endometrial cancer. SAFETY OBJECTIVE: I. To compare progression free and overall survival in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive ICG dye via injection and undergo sentinel lymph node mapping during standard minimally invasive hysterectomy. Lymph nodes around the uterus may be removed if the mapping cannot be completed. Successful mapping requires no additional removal of lymph nodes. ARM 2: Patients receive ICG dye via injection and undergo sentinel lymph node mapping during standard minimally invasive hysterectomy. Additional lymph nodes around the uterus are removed per standard of care. Patients in both arms also undergo imaging as clinically indicated. After completion of study intervention, patients are followed every 3 months for one year and at 18 and 24 months.

Nct (2022). "Implementation of a Multimodal Prehabilitation Program in Robotic Oncological Surgery." ClinicalTrails.gov.
	The main elements of established enhanced recovery after surgery (ERAS) include a minimally invasive surgical approach when feasible, locoregional analgesia, limited use and duration of drains, minimized blood loss and perioperative fluid administration, early oral re‐nutrition, respiratory physiotherapy, and early mobilization. These pathways have demonstrated to be beneficial in the oncological surgery field by reducing hospitalization costs and peri‐operative complications, while maintaining suitable oncological and functional outcomes. It has to be emphasized that patients who are active and well‐functioning prior to surgery, have fewer complications, recuperate faster, and experience better recovery compared to their less fit counterparts. Recently, prehabilitation as a strategy to begin the rehabilitation process before surgery gains more interest. Although there is no single definition of prehabilitation available, this intervention aims to actively prepare patients before surgery through exercise, nutritional support, psycho‐cognitive training or a combination thereof. Current literature on prehabilitation is broad and heterogenous. Ploussard et al initiated a multimodal one‐day prehabilitation program in patients before robotic radical prostatectomy involving urology nurses, anaesthetic nurses, oncology nurse specialists, anesthesiologists, dieticians, physiotherapists etc, and observed significant improvement in terms of reduction in length of stay, blood loss, and operative time, and an increase in the proportion of ambulant surgery. Santa Mina et al observed that patients following a home‐based moderate‐intensity exercise prehabilitation program prior to radical prostatectomy were more fit i.e have a greater score on the 6 minutes' walk test, four weeks postoperatively compared to a control group. Regrettably, this study couldn't demonstrate a difference in length of stay or complication rate. To date, evidence for efficacy of prehabilitation in gynaecological cancer patients is limited. Several reviews and a meta‐analysis indicate that the level of evidence suggesting that prehabilitation may improve postoperative outcomes is low. Moreover, there is a wide variability in applied preoperative prehabilitation programs i.e, with a uni‐ or multimodal approach, home‐based or supervised, differences in intensity and a variety of outcomes. Therefore, there is a need for randomized controlled trials with low risk of bias and clearly defined outcome parameters to clarify the potential benefit of prehabilitation for patients Hence, the primary goal of this randomized pilot study is to determine the feasibility of the implementation of a multimodal prehabilitation program in patients undergoing robotic oncologic urological or gynaecological surgery in a Belgian tertiary center in terms of protocol adherence and recruitment rate. Study design This is an observer‐blind, randomized controlled, superiority trial. All participants will receive standardized perioperative care according to established ERAS protocols (main elements include a minimally invasive surgical approach when feasible, locoregional analgesia, limited use and duration of drains, minimized blood loss and perioperative fluid administration, early oral re‐nutrition, respiratory physiotherapy, and early mobilization). The standard preoperative pathway includes risk assessment, medication management and perioperative blood management. Randomization Patients will be randomly assigned in a 1:1 ratio to either of the two study groups: an intervention group undergoing the prehabilitation program and a control group. A block randomization of 4, stratified per type of surgery, will be performed using a computer‐generated random allocation sequence, created by the study statistician. Allocation numbers will be sealed in opaque envelopes, which will be opened in sequence by an unblinded member of the study team after enrollment of a patient into the study. The randomization list will remain with the study statistician for the whole du ation of the study.

Nct (2022). "Improving Care for Women With Urinary Incontinence (EMPOWER)." ClinicalTrails.gov.
	In the study, patients will be screened in primary care offices for symptoms of urinary incontinence. Women with positive screening results will be asked if they are interested in participating in an implementation study where women will be assigned to one of the three following groups: 1. Usual Care plus Patient Educational Opportunities ‐ The patient's urinary incontinence will be managed using standard of care treatment by the patient's primary care provider. Patients will be offered educational opportunities about urinary incontinence. 2. Nurse Navigation ‐ Along with the treatment described for "Usual Care plus Patient Educational Opportunities," a nurse navigator will work with the patient to implement behavioral changes and provide education and physical therapy options. In addition, the navigator will be available to answer the patient's questions in a timely fashion and help the patient move through the care pathway. 3. Nurse Navigation and ChatBot ‐ Along with the treatment described for "Usual Care plus Patient Educational Opportunities" and "Nurse Navigation," this group will include a ChatBot feature which will allow a patient to directly and privately communicate with an artificial intelligence‐driven ChatBot, also known as a "conversational agent," that will provide education and help the patient navigate the care pathway. All participants will complete questionnaires throughout their enrollment and data will be collected from medical records. The study team will analyze the data at six months after the original appointment/study enrollment, assess adherence to therapy and how the therapy impacted the outcomes the team hopes to improve, such as improvement in symptoms. The study will be implemented over three subsequent time periods called Wave 1, Wave 2 and Wave 3 with primary care practices from two geographic regions being involved in each wave (6 regions total). Participants in Wave 1 will be followed for a total of 18 months, while participants in Wave 2 will be followed for a total of 12 months, and participants in Wave 3 will be followed for 6 months. Primary care providers at all participating practices will be offered educational opportunities related to urinary incontinence.

Nct (2022). "Intradetrusor Botulinum Toxin A for OAB Via 1 Versus 10 Injections: a Randomized Clinical Trial." ClinicalTrails.gov.
	Intradetrusor (bladder) Botulinum toxin A (BTA or Botox®) is a well‐established treatment for urinary urgency incontinence (UUI).[1,2] While this treatment's efficacy in comparison to alternative therapies including anticholinergic medications and sacral neuromodulation for treatment of UUI has been studied, the ideal number of injection sites within the bladder has not been well established. [3,4] Intradetrusor BTA injections are often completed as an office procedure while the patient is awake. Each injection site can cause discomfort for the patient during the procedure. Urinary tract infection and urinary retention are risks associated with this procedure and could potentially be related to number of injection sites. Currently, there is a lack of information in the literature regarding the optimal number of intravesical BTA injection sites. Prior studies evaluated efficacy using 100u BTA spread across 20 injections sites, however current practices at local institutions safely use 10 injections sites based on studies showing similar effect and adverse event profiles between use of 10, 20, and 40 injection sites.[5,6] Research using animal models has shown diffuse distribution of BTA within the entire detrusor muscle after just a single BTA injection at one site.[7] This has been corroborated in human studies.[8] A recently published observational pilot study shows promise for single site intradetrusor Botox® injection as it reported a lower rate of urinary retention and similar durability.[9] Similar clinical efficacy with only one to three intravesical BTA injection[s] has also been reported.[10] In this study, participants will be randomized to receive 100u BTA via intradetrusor injection at one injection site (experimental) versus 10 injection sites (control). Investigators hypothesize that one injection will have similar efficacy to multiple injections and potentially better tolerability and patient satisfaction, due to decreased procedure time and less pain, along with potential for lower adverse event rates, specifically urinary retention and urinary tract infections.

Nct (2022). "Intraoperative Clonidine for Postoperative Pain Management in Patients Undergoing Surgical Treatment for Endometriosis." ClinicalTrails.gov.
	Background with aim: Acute postoperative pain is a major and common concern for the large number of patients who undergo surgery each year. Despite advances in pain management strategies, many patients continue to suffer from moderate‐to‐severe pain during the early postoperative period. This is concerning as unrelieved pain can result in decreased patient satisfaction, increased morbidity, prolonged hospital length‐of‐stay and increased risk of persistent pain. Effective treatment of acute postoperative pain should therefore be prioritized. Opioid analgesics remain the mainstay treatment for postoperative pain. The potential benefits of opioid therapy for acute pain are short‐term pain control. However, there are several potential harms associated with opioid use which may outweigh the benefits including sedation, nausea, vomiting, constipation and risk of long‐term use. In this respect, a single dose of clonidine could provide stable analgesia and potentially reduce the need for shorter‐acting opioids. Therefore, the investigators decided to carry out the present study with the aim to examine the analgesic efficacy and safety of intraoperatively administered intravenous clonidine in patients undergoing surgical treatment for endometriosis on postoperative opioid consumption, pain intensity and opioid‐related side effects. Method: 120 patients undergoing surgical treatment for endometriosis will be included in this prospective, randomized, double‐blind, controlled trial with two arms: an intervention arm (clonidine 150 microgram) and a control arm (isotonic saline). The study will be GCP‐monitored, and is approved by the Danish Medicines Agency (2022064017) and the National Committee on Health Research Ethics (2209269). Hypothesis: The investigators hypothesize that a single dose of intraoperatively administered intravenous clonidine will be effective in reducing postoperative opioid requirements, pain intensity and opioid‐related side effects.

Nct (2022). "Intraperitoneal Lidocaine in Ovarian Cancer Surgery." ClinicalTrails.gov.
	This is a prospective, randomized, controlled clinical study. Sixty patients were expected to participate in a centralized randomized study method divided into two groups of 30 patients per group: the intraperitoneal analgesic group and the normal saline control group. Standard routine anesthesia was performed in both groups using the same method, and intravenous analgesia pump was routinely used in clinical use after surgery. The intraperitoneal analgesic group was continuously pumped with local anesthetics into the abdominal cavity, while the control group was pumped with normal saline. Visual analogue pain score (VAS), amount of remedial analgesia and use of analgesia pump were recorded at 1, 2, 4, 8, 12, 24, 36, 48, 60 and 72 hours after operation. Record the time when the patient began drinking and eating, and the time when gastrointestinal function (defecation or exhaust) recovered. The time of starting to walk on the ground (including the time of needing attendant assistance or not) and the time of meeting the standard of postoperative discharge preparation. Perioperative peripheral blood samples were collected for five times (T0 before anesthesia induction, T1 after tracheal extubation, T2 on the morning of the first postoperative day, T3 on the morning of the second postoperative day, and T4 on the morning of the third postoperative day), and inflammatory factors and tumor‐related indicators were monitored. Adverse reactions were recorded. The prognosis of the patients was followed up 5 years after operation.

Nct (2022). "Intrauterine Insemination and Nursing." ClinicalTrails.gov.
	Infertility treatment is a stressful and anxious process that begins when couples are diagnosed with infertility. Infertility treatment is a process that requires the active participation of couples against emotional and physical difficulties. In addition to intensive routine and surgical procedures, the treatment process is a period in which couples should be in constant communication with healthcare professionals. In Turkey, it is estimated that 10‐20% of the couples are diagnosed with infertility. In the evaluation of infertile couples,Intrauterine Insemination is a simple, safe, and minimally invasive procedure to the process of injecting washed sperm into the uterine cavity close to ovulation. Sperm cells taken from men are injected directly into the uterus and left at a point closer to the fertilization point. The aim of this study is to investigate the effect of virtual reality glasses use and therapeutic touch on pain, anxiety and patient satisfaction in women during intrauterine insemination procedure. This randomized controlled study will conduct at Ondokuz Mayis University Training and Research Hospital, Infertility polyclinic between january 2022 and June 2022. Volunteer women undergoing Intrauterine Insemination will be include. Participants will randomly assigned to the intervention or the control group using a computer‐generated list. A data collection form including socio‐demographic and obstetric characteristics such as age, educational status, duration of infertility, previous pregnancies, births, abortion/curettage numbers, Spielberger State Anxiety Scale and Visual Analog Scale scores will use for each patient. After obtaining written informed consent, the data collection form, Spielberger State Anxiety Scale and VAS scoring scale (pain and nursing satisfaction) were applied to both groups by face to face interview during the day giving appointment for Intrauterine Insemination. Immediately after the questionnaires will apply, the nurse gave virtual reality glasses. and glasses will be put on before the process starts and training will be given to continue watching the video while wearing the glasses for 30 minutes. Second group participants the nurse researcher will start the application by taking an appropriate hand of the patient between his hands and hold it for 30 minutes. Participant in the control group received standard care (verbal information about procedure and a short written information about the procedure) and no intervention (virtual reality or therapeutic touch) was performed.The IBM SPSS (Statistical package for the Social Sciences) 23.0 package program was used to evaluate the data obtained in the study.

Nct (2022). "Invasive PGT-A Embryo Selection Versus Non Invasive PGT-A Assisted Embryo Selection." ClinicalTrails.gov.
	A randomized prospective study focusing on subfertile women undergoing IVF treatment followed by embryo transfer on the blastocyst stage. Women assigned to group A proceed to embryo transfer, after invasive PGT‐A embryo selection, while women of group B after non‐invasive PGT‐A assisted embryo selection. IVF outcomes, regarding the success rate of the trasnfer and the time required to achieve conception is studied in both groups.

Nct (2022). "Itraconazole in Advanced Ovarian Cancer." ClinicalTrails.gov.
	This is a randomized, placebo controlled; parallel study that will be conducted on 66 female patients with advanced epithelial ovarian carcinoma (stage III and stage IV). The staging of the disease will be done according to 8th edition of American Joint Committee on Cancer (AJCC), TNM staging. The patients will be recruited from Oncology Department, Tanta University Hospital. The patients will receive a combination of paclitaxel and carboplatin chemotherapy with or without itraconazole. Randomization will be carried out based on hospital admission days where the patients will be randomized into the following two groups to compare effect of adding Itraconazole to paclitaxel and carboplatin versus placebo to paclitaxel and carboplatin.

Nct (2022). "IV Oxytocin for Post Operative Pain After Minimally Invasive Hysterectomy." ClinicalTrails.gov.
	‐ Patients will be recruited for participation in this study while they are in pre‐operative holding area before surgery. ‐ Once the patient is recruited and consented the patient, they will be randomized for either the intervention group (IV oxytocin) or control group (0.9% normal saline). ‐ In the holding area, a pre‐operative pain questionnaire, including the State‐Trait Anxiety Inventory (STAI‐6) questionnaire and the Daily Pain Catastrophizing Scale (DPCS), will be performed. ‐ The STAI‐6 is a validated, short 6‐question form to assess anxiety. It is one of the most frequently used measures of anxiety in applied psychology research and has been used to assess anxiety in perioperative patients and to assess the potential of a patient to have higher postoperative pain and opioid requirements and a greater likelihood to use chronic opioids or develop chronic pain. ‐ The DPCS is a validated, short questionnaire to assess measure of catastrophizing in the context of actual or anticipated pain. Similar to the STAI‐6, it has been shown to predict patients who experience higher postoperative pain and opioid requirements and those with a greater likelihood of using chronic opioids or developing chronic pain. ‐ Both groups (intervention and control) will be treated pre‐operatively with acetaminophen 1000 mg and gabapentin 300 mg orally. ‐ The Investigational Research Pharmacy will be informed and prepare medication or placebo. ‐ The primary anesthesiology team receive either the study medication or placebo in 500 ml bag of labeled as "Oxytocin Study Drug for IV infusion". ‐ A recommended "Intra‐Operative Analgesia Management" algorithm will be given to the primary anesthetic team. The recommended algorithm for intra‐operative analgesia management will include the following recommendation: ‐ Fentanyl 100 mcg IV for induction. ‐ Dexamethasone 8 mg IV after induction but prior to incision. ‐ Small, titrated doses of Hydromorphone IV boluses (0.2‐0.4 mg) during the operation and before emergence according to primary team judgment. ‐ Ketorolac 30 mg IV at skin closure unless otherwise contraindicated. ‐ The infusion will be started intra‐operative once the uterus is removed and will continue to run until completion of the medication or discharge from PACU criteria are met, whichever occurs first. ‐ Other aspects of each patient's routine clinical care will continue as per the attending physician under whom the patient is admitted, regardless of treatment arm status. ‐ The intervention group will be treated with oxytocin 30 IU in 500 ml IV at a rate of 5 IU/h (83.33 ml/h). The control group will be given IV 0.9% saline infusion at the same rate of 83.3 ml/h. The primary care team (anesthesia, surgery and nurses), research team and the patient will all be blinded for the treatment. ‐ In the PACU, a brief postoperative pain questionnaire will be done, including the Surgical Pain Scales (SPS). ‐ The SPS is a validated scale that consists of 4 items that measure pain at rest, during normal activities, during work/exercise and quantify the unpleasantness of worst pain. This scale has been validated in a number of different types of postoperative pain, including women after gynecologic surgery. ‐ Vital signs, NRS pain scores and opioid consumption at PACU will be collected from the patient's medical record. ‐ Patients whose surgery was converted to open, EBL >500 ml or any other surgical complication that necessitates a hospitalization will be excluded from the trial. ‐ For secondary outcomes, including total opioid consumption in 24, 48, and 72 hours and pain scores at POD1, 2, and 3, an online survey will be done at POD1, 2, and 3. For patients who do not complete the survey, a phone call from a study staff member will be performed to complete all questions not completed with the online form.

Nct (2022). "Kinesio Taping With and Without Exercise Program in Primary Dysmenorrhea." ClinicalTrails.gov.
	Primary dysmenorrhea (PD) is a common gynecological problem among adolescents and adult women. Treatment of PD includes various drugs and therapies such as kinesio taping (KT) and exercise. There are various studies that have individually explored the effects of KT and combined exercises. A randomized controlled trial (RCT) will be conducted to compare the effects of KT combined a combined exercise program and the effects of KT alone on pain and quality of life in females suffering from PD. The study will involve 45 women who experience dysmenorrhea. divided into three groups, group A, group B and Group C. Group A will receive the combined exercise program (The exercise protocol which included stretching exercises, yoga position, Kegel exercise, bridging exercise) for 45 minutes with 3 sessions per week for eight weeks. The Group A will receive KT intervention for two days per week from the estimated day of ovulation till the next period occurs, for eight weeks. The group B will receive KT that is used to treat the symptoms of primary dysmenorrhea for 45 minutes with 2 sessions per week for eight weeks. The Group C will receive conventional therapy with 3 sessions per week to eight weeks. Numeric pain rating scale (NPRS), Short form 36 Questionnaire (SF‐36) and Menstrual symptom questionnaire (MSQ) will be used to assess the pain and quality of life at baseline and at the end of 8th week.Total duration of study will be six months. Physiotherapy can be a very successful treatment for PD with the benefit that the patient may occasionally be able to carry out the treatment independently. recommendations for manual therapy, acupressure, Kinesio tape, electrotherapy, and other forms of treatment. There have also been discussions about therapeutic activities or progressive relaxation techniques. It is stated in literature that most effective exercise programs were stretching and isometric exercises for 8 weeks for pain intensity and duration, yoga for 12 weeks for pain intensity and quality of life, and aerobic exercises for 12 weeks for quality of life and KT for 12 weeks for pain and quality of life in PD. There are many various tapes available, each with a different type, substance, and application, according to the most recent research in 2021.

Nct (2022). "Laparoscopic Combined Hypo Gastric Neural Plexus Block and Uterosacral Nerve Block for Patients With Chronic Idiopathic Pelvic Pain." ClinicalTrails.gov.
	This prospective randomized controlled study will be conducted at Eldemerdash hospital. 60 patients will be included with the following criteria: . Intraoperatively, all patients were monitored by standard monitoring. All Patients will be assigned randomly by using computerized program to one of the two equal groups. Patients will be (thirty patients per group): Group A ; thirty patients will do laparoscopy for diagnosis of the causes of chronic pelvic pain then injecting 5 ml normal saline for hydro dissection of the retroperitoneal space at the level of the sacral promontory then30 ml (14 ml Marcaine +14 ml normal saline+2ml betamethasone) are injected. Group B; thirty patients will do laparoscopy for diagnosis and conventional surgical treatment of the causes of pelvic pain then injecting 5 ml normal saline for hydro dissection of the retroperitoneal space at the level of the promontory followed by 30 ml (14 ml Marcaine +14 ml normal saline+2ml betamethasone) then injecting 5 ml ( 2.5 marcaine+1ml betamethasone +1.5 ml normal saline) 2 cm away from the cervix at the uterosacral ligament on each sides. Pain score ( visual analogue score) was assessed before surgery (basal) and after completion of laparoscopy 4hr, 12hr, 24hr, 48hr, 1, 4, 8,12, 16,20 and 24 weeks. Visual analogue scale: No pain Moderate Worst Pain 0 1 2 3 4 5 6 7 8 9 10 Duration of pelvic pain relieve after laparoscopy up to 16 weeks,side effects like urinary retention, constipation were recorded after completion of laparoscopy 4hr, 12hr, 24hr, 48hr, 1week, 4weeks, 8 weeks, 12 weeks and 16 weeks. Urinary retention will be treated by reassuring the patients and catheterization as it usually resolves after 2‐3 days, constipation will be treated by reassuring the patients and purgatives as it usually resolves after 2‐3 days. Postoperatively, all patients were transferred to postoperative care unit (PACU) and monitored every 10 min until discharge.

Nct (2022). "Laser and High Intensity Tesla Magnetic Stimulation (HITS) for Stress Urinary Incontinence (SUI)." ClinicalTrails.gov.
	This study is a single‐centre, two‐arm randomized control trial study conducted according to Helsinki Declaration. Women with symptoms of stress urinary incontinence (SUI) (stress or mixed with stress incontinence as the predominant symptom) will be enrolled. The efficacy and safety of combined treatment with non‐ablative intravaginal Er:YAG laser procedure and high intensity Tesla magnetic stimulation will be compared to the treatment of non‐ablative intravaginal Er:YAG laser alone.

Nct (2022). "Laser at Lumbar Acupoint on Pain and Quality of Life in Chronic Pelvic Pain." ClinicalTrails.gov.
	Thirty six females with chronic pelvic pain will participate in this study. The patients will randomly be divided into two equal groups; the control group will receive non‐steroidal anti‐inflammatory drugs in the form of Brufen (Ibuprofen), 400 mg, 3 times per day after meals, for 6 weeks, as will described by their gynecologist. and the study group received the same treatment and low‐level laser at lumbar sensitized Acupoint, three times per week for four weeks. The evaluation methods by visual analogue scale (VAS), pain sensitivity was evaluated by measuring mean values of pressure pain thresholds (PPT) using a Pressure Algometer, while the quality of life was evaluated by the 12‐Item Short‐Form Health Survey (SF‐12) before and after the treatment

Nct (2022). "Letrozole as Maintenance Therapy for Post-surgical Endometrial Cancer Patients With NSMP." ClinicalTrails.gov.
	This is an open label multi‐center superiority randomized controlled trial, aimed to investigate the effect of Letrozole as maintenance therapy on the prognosis of post‐operative endometrial cancer patients with non‐specific molecular profile. The molecular classification of non‐specific molecular profile (NSMP) is the most common type of endometrial cancer. Reducing the recurrence rate and improving the survival rate in patients with NSMP can effectively improve the overall prognosis of endometrial cancer. NSMP endometrial cancers are featured as high sensitivity to hormones, which could be a potential target to improve the prognosis. Antiestrogenic therapy might be an effective treatment to improve the prognosis of NSMP endometrial cancer with high risk of recurrence and metastasis. Letrozole, an oral non‐steroidal aromatase inhibitor, might have positive impact on those patients as maintenance therapy after first‐line postoperative adjuvant treatments. The current standardized treatment for intermediate‐high risk endometrial cancer patients after chemotherapy and radiotherapy includes none but observation alone. However, with little adverse effects, low cost and easy availability, the practice of letrozole in hormonally‐responsive breast cancer after surgery added to evidence to have an improvement in the prognosis in intermediate‐high risk endometrial cancer. Thus, it is necessary to carry out a randomized trial to investigate the role of letrozole as maintenance therapy after postoperative adjuvant treatment in the prognosis of intermediate‐high risk endometrial cancer. This study were approved by the Ethics Committees of Obstetrics and Gynecology Hospital of Fudan University and all other institutes. Before initiation of study procedures, written informed consent will be obtained from each patient regarding risks of treatments and agreement of using their clinical data for research purpose. This is a multicentered, open‐label, randomized clinical trial. Randomization will be carried out in each center. A computer‐based procedure of simple randomization (SPSS for Mac, version 22.0; IBM ) will be used for participant enrollment and randomization. Before an individual is successfully enrolled, her treatment assignment will remain concealed. This trial will be open label: patients and study physicians were aware of treatment assignment. Patients will be stratified into 3 groups by operative staging (FIGO 2009), pre‐ and post‐ operative imaging assessment and residual tumor condition after surgery: stage I/II without early postoperative residues, stage III/IV without late postoperative residues and patients with postoperative residues. Eligible patients in each stratification of each center will be randomly assigned (1:1) to receive: Arm 1. Letrozole 0.5mg qd po for 2 years after postoperative adjuvant therapy, or Arm 2. Observation alone without any other therapy after postoperative adjuvant therapy. A definitive surgery should be performed after the latest NCCN guidelines, including a hysterectomy with/without bilateral salpingo‐oophorectomy plus sentinel node biopsy or pelvic lymph node sampling with para‐aortic lymph node sampling. All the patients must meet the criteria to have postoperative adjuvant treatments, excluding patients with low prognostic risk: stage IA endometrioid + low‐grade* +lymphovascular space invasion (LVSI) negative or focal, or those requiring no adjuvant therapy after surgery. Postoperative adjuvant treatments are carried out following the latest NCCN or ESGO guidelines according to doctors' choice. Molecular classification must be performed and proved be to non‐specific molecular profile (NSMP) according to diagnostic algorithm for the integrated histomolecular endometrial carcinoma classification (WHO classification of tumors, 5th edition, female genital tumours). Statistical analyses On the basis of data from previous studies (Molecular Classification of PORTEC‐3 Trial；GOG‐249；GOG‐99), the 3‐year PFS is expected to be 80% in the observ ion group. Letrozole as maintenance therapy would improve 3‐year PFS to 90%, which is considered as superior to observation alone. An accrual of 299 patients in 3 years will provide the study with adequate power (90%) to detect a clinically relevant absolute difference of 10% in 3‐year PFS (90% vs 80%) between both groups (one‐sided test, a=0.05), with a lost follow up rate ≤10%. Analyses will be done firstly by intention to treat.

Nct (2022). "Lidocaine for Pessary Check Pain Reduction." ClinicalTrails.gov.
	The purpose of the study is to investigate the effects of lidocaine jelly on patient pain at the time of office pessary removal and reinsertion. All patients presenting to the University of South Florida Urogynecology clinic for a pessary maintenance appointment or "pessary check" will be screened as potential study participants. After being informed of risks and benefits of participation, informed consent will be obtained. Patients will be randomized into two groups: the control group or experimental group. The patient will complete a brief questionnaire and pain assessment using a Visual Analog Scale (VAS). Patients will be blinded. The investigators will be unblinded. The investigators will apply the jelly (lidocaine vs lubricating). The participant will have an equal chance of being in the control arm or experimental arm. After 5 minutes, the investigator will assess the patient's genital hiatus with valsalva and proceed with pessary removal per the investigator's routine. The patient will complete another VAS to indicate pain level after pessary removal. The investigator will perform a speculum exam per routine and then reinsert the pessary. The patient will complete a final VAS to indicate level of pain after pessary reinsertion along with a brief final questionnaire.

Nct (2022). "Lifestyle Change in Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	This project aims to compare "diet" and "diet and exercise combination" interventions in obese women with polycystic ovary syndrome. This project will be carried out in the Dokuz Eylül University Research and Application Hospital gynecology outpatient clinic between June 1, 2022 and June 1, 2024. The purpose of the project will be explained to women who meet the sampling criteria, and their informed consent will be obtained. A prospective and randomized comparison of "diet" and "diet and exercise combination" interventions, which are among the first‐line treatment lifestyle changes recommended for PCOS, will be done. In the project, 33 women in the first group will receive "diet" intervention for 12 weeks, and 33 women in the second group will receive "diet and exercise combination" intervention. "Descriptive Characteristics Form" will be filled in for both groups, then at the beginning and at the end of the project, routine ultrasonography and laboratory test parameters for PCOS diagnosis criteria and menstrual cycle characteristics will be recorded, hirsutism score, alopecia score and acne level will be evaluated, the Utian Quality of Life Scale, Body Appreciation Scale, and the Short Form of the Oxford Happiness Questionnaire will be filled out. Body composition analysis will be performed in both groups at the beginning of the project, in the fourth and eighth weeks, and personal dietary recommendations will be given. Kitchen scales will be given to both groups to adapt to dietary recommendations and a mobile nutrition application will be used to record their diets. Person‐specific exercise recommendations will be given to the second group at the beginning of the project, in the fourth and eighth weeks. In addition, women will be informed with a guide to behavioral changes specific to PCOS, which will be prepared specific to their group. Exercise parameters will be recorded by giving the same mobile application. Mobile nutrition application data will be collected via e‐mail in the fourth, eighth and twelfth weeks of the project.

Nct (2022). "Live Birth After Letrozole-stimulated Cycles Versus Hormone Replacement Treatment Cycles for the First Frozen Embryo Transfer in Women With PCOS." ClinicalTrails.gov.
	This is a multicenter randomized controlled trial comparing the efficacy and safety of two endometrial preparation protocols for the first frozen embryo transfer cycle in PCOS with whole embryo freezing. Subjects will be randomized to letrozole‐stimulated group or hormone replacement treatment group in their first frozen embryo transfer cycle, and their pregnancy and perinatal outcomes during this cycle will be followed up and analysis.

Nct (2022). "Local DHEA and Estradiol on Dyspareunia in Postmenopausal Women." ClinicalTrails.gov.
	Vulvovaginal atrophy (VVA) is a condition characterized by vaginal dryness, itching, burning, irritation and dyspareunia. The condition is mainly due to estrogen deficiency and is common during and after menopause. Furthermore, androgens may have an important function in these symptoms. The purpose of the study is to compare vaginal estrogen with vaginal dehydroepiandrosterone (DHEA, an androgen precursor) on dyspareunia (primary outcome), a symptom of VVA in postmenopausal women. Secondary outcomes are total symptom score of VVA (vaginal dryness, irritation/itching, maturation index, pH), clinical signs of VVA, sexual function, urogenital symptoms, vaginal histomorphology, sex hormone levels and short‐term safety. The hypothesis of the study is that the treatments will have a similar effect on dyspareunia while DHEA, through local androgenic effects (eg growth of muscle tissue and nerve density in the vaginal wall), may be more effective in treating other related symptoms such as sexual dysfunction. 170 postmenopausal women will be randomly assigned to treatment with either vaginal estrogen (Vagifem) or vaginal DHEA (Intrarosa). The women are examined at the start of the study, after 4 weeks of daily application and after another 8 weeks of treatment with twice a week application of the vaginal treatment. The study is expected to provide increased knowledge about the effect of the treatments of VVA in postmenopausal women as well as whether vaginal DHEA has additional positive effects on sexual function compared to vaginal estrogen.

Nct (2022). "Low Versus High Intensity Laser Therapy on Primary Dysmenorrhea." ClinicalTrails.gov.
	This study will be conducted on fifty two participants suffering from primary dysmenorrhea selected from Cairo Specialised Hospital( Department of Obestetrics and Gynaecology). All females will be randomly divided into two equal groups: ‐ Group (A): lt will include 26 participants suffering from primary dysmenorrhea who will receive low intensity laser therapy 3 sessions per cycle for 3 consecutive cycles (one session will be applied the day before menstruation and the other two sessions on the 1st and 2nd days of menstruation). ‐ Group (B): It will include 26 participants suffering from primary dysmenorrhea who will receive high intensity laser therapy 3 sessions per cycle for 3 consecutive cycles (one session will be applied the day before menstruation and the other two sessions on the 1st and 2nd days of menstruation ). All females will be given a full explanation of the study protocol and a consent form will be signed by each female before entry in this study

Nct (2022). "Low-Carb Versus Mediterranean Diet in PCOS." ClinicalTrails.gov.
	The study aims to clarify the impact of nutritional recommendations for women with polycystic ovary syndrome on clinical, metabolic and hormonal parameters, inflammatory markers and gut microbiota . Women with PCOS are randomized into 2 treatment groups: one group on a low‐carbohydrate diet and the other on a Mediterranean diet. The adhearance to a prescribed diet will be controlled through food intake diaries using a mobile application with electronic reporting forms.

Nct (2022). ""Mamá, te Entiendo" App-based Intervention for Reducing Depressive Symptoms in Postpartum Women." ClinicalTrails.gov.
	Background Chile has a high prevalence of postpartum depression and a significant treatment gap. Some barriers to postpartum depression care uncover the need for more easily accessible and lower‐cost interventions. Chile's high utilization of digital technologies across all social strata and the increased use of pregnancy and parenting apps open the possibility of delivering interventions through mobile devices. Cognitive‐behavioral internet‐based interventions have proven to be effective in reducing symptoms of depression in high‐income countries. However, in Chile, this is an underdeveloped field. This trial aims to examine the feasibility and acceptability of a guided 8‐week cognitive‐behavioral app‐based intervention for Chilean postpartum women with depressive symptoms. Methods and design Study Design This is a mixed‐methods feasibility and acceptability study of an app‐based intervention for reducing postpartum depression symptoms. A two‐arm, small‐scale randomized controlled trial will be conducted with postpartum women with minor or major depression. Women will be randomly assigned to the intervention group (internet‐based intervention: "Mamá, te entiendo" /"Mom, I get you") or the control group (waitlist: WL). The three primary data collection points for study participants in the intervention group and WL group are as follows: baseline (pre‐treatment: T0), post‐treatment (8 weeks from randomization: T1), and 1‐month follow‐up (12 weeks from randomization: T2). A sample size of 33 participants per group was set. A qualitative evaluation will be conducted to have more knowledge about participants' perspectives on the intervention and study procedures. Recruitment Recruitment will be conducted online through advertisements on social media platforms. The ads will include general information on the study aims and inclusion criteria and will be linked to a web‐based depression symptomatology assessment. Potential participants will be contacted for further eligibility assessment. No incentives for participation will be provided so that the endpoint of participant acceptability will not be confounded. Randomization Women who meet inclusion criteria will be randomized to "Mamá, te entiendo" or WL. An independent person not involved in the study will generate the allocation sequence. Stratified randomization will be conducted according to depressive symptom severity. Researchers will be blind to the randomization process and will be notified through email regarding participant allocation by an independent researcher. Once randomized, participants and research personnel will not be blinded to group condition. Following the notification, participants will be contacted over the telephone to inform them of their assigned group (i.e., intervention or WL). The intervention group will receive instructions for registering into the app. Intervention Condition: "Mamá, te entiendo" ("Mom, I get you") Participants in this condition will receive a guided, app‐based, cognitive‐behavioral, 8‐week intervention for postpartum depression symptoms. It also includes some elements from attachment and mentalization theories. "Mamá, te entiendo" was developed based on the CeHRes Roadmap through a participatory process that involved continuous evaluation cycles. Ten focus groups were conducted with perinatal women and healthcare professionals, and five usability interviews with potential end users. "Mamá, te entiendo" consists of the following sections : ‐ Main and optional modules. The intervention consists of six main sequential modules and three optional modules. The main modules address the following: Psychoeducation on depression, How the cognitive‐behavioral approach works, Identifying thinking errors, Cognitive restructuring, Problem‐solving, and Behavioral activation. The optional modules address: Psychoeducation on anxiety, Exposure strategies, and Communicational Skills. Five case examples of mothers illustrate depressive symptoms and techniques. There is also an introductory mo le describing the app's functioning (without therapeutic content), and a guide about maintaining changes is displayed when the last main module is completed. ‐ Homework exercises (Workbook). All modules except the two psychoeducational ones include homework. All homework exercises can be accessed through a specific section in the app called "Workbook". Participants will receive feedback from an e‐coach. They also can contact the e‐coach to solve doubts about the app content and exercises. The e‐coaching protocol of the Caring Universities Project was adapted for this intervention. ‐ Infographics. Another section of the app includes infographics about other relevant topics: 1) Guide to healing, 2) How to strengthen the support network, 3) Postpartum rage, 4) The postpartum body, 5) Dealing with doubts/comparison/over information, 6) Mentalizing my baby, 7) The couple's relationship in the postpartum period, 8) Returning to work after the maternity leave. ‐ Reading for the support network. A shareable document with reading about how to support a loved one struggling with depression symptoms is included. ‐ Resources section. A resources section includes links to websites and documents of interest. WL Condition Participants in the WL condition will receive the same assessments as those in the intervention condition. Participants allocated to WL may access their local mental health services during their waiting period. In Chile, patients diagnosed with depression by a general practitioner have guaranteed access to treatment at low or no cost. Treatment varies according to depression severity, with group or individual therapy, alone or combined with pharmacotherapy. After the follow‐up assessment, the WL group will be offered access to the intervention. Data collection All data will be collected online via video call (interviews) or web platform (self‐report questionnaires). Semi‐structured acceptability interviews will be recorded and transcribed. Analyses The primary outcomes are feasibility and acceptability variables, mainly; recruitment and eligibility rates, intervention and study adherence, and participants' intervention satisfaction, use, and engagement. Secondary outcomes include depression symptomatology and diagnosis, perceived social support, mother‐infant bonding, and maternal satisfaction and self‐efficacy. Descriptive statistics will be reported, including the means and standard deviations (SDs) or medians and interquartile ranges for each questionnaire at T0, T1, and T2. For preliminary efficacy, data will be analyzed following CONSORT guidelines; between‐group comparisons will be by intention‐to‐treat. Comparison between groups will use repeated measures analysis of covariance (ANCOVA) with adjustment for baseline in a random‐effects model. Interaction between time and group will be assessed (for changes in group effects with time), and, in the absence of such an interaction, the overall difference between groups across the two follow‐up assessments will be calculated (95% CIs and p values). The qualitative data from the interviews will be analyzed by two independent coders using thematic analysis. Themes will be identified, described, and subsequently categorized.

Nct (2022). "Maternal Well-being in the Postnatal Stage." ClinicalTrails.gov.
	Participants will be randomly assigned to the CBT group or the PPI group. Both groups will be treated identically except for the type of intervention. Group assignment will be blind to both patients and investigators. Both interventions have 10 weekly sessions. Sessions will be in groups and online. CBT includes 3 modules: behavioral activation, cognitive restructuring, and interpersonal skills. Main contents (10 sessions): (1) Symptoms of Depression. Myths about motherhood. CBT approach; (2) Stress and Anxiety. Relaxation; (3 and 4) Increase pleasurable activities. Balance in life. To manage time; (5) Management of negative thoughts. Health concerns; (5 and 6) Increase positive thoughts; (7) social skills; (8) Communication skills and parner support; (9) Plan for the future. New routines and strategies; (10) Relapse prevention. CBT has been shown to be effective in reducing depressive symptoms and modifying attentional biases (Pearson et al., 2013). On the other hand, a new protocol of positive interventions adapted for women after maternity (PPI) will be designed and applied. This multicomponent protocol includes interventions that have already been empirically validated in treating depression. PPI includes 2 modules: hedonic well‐being and eudaimonic well‐being. Main contents (10 sessions): (1) Symptoms of Depression. Myths about motherhood. PPI approach; (2) Mindfulness and positive emotions; (3) Gratitude and savoring; (4) Emotion regulation (5) Positive relationships and social support; (6) Compassion; (7) Personal strengths; (8) Goals and values; (9) Resilience; (10) Relapse prevention.

Nct (2022). "Menoupausal Symptoms and Aromatherapy." ClinicalTrails.gov.
	As a result of the effect of aromatic oils on the central nervous system, relaxation, sedation or stimulating effects occur and the information flow reaching the brain with the stimulation of the central nervous system. Thanks to this, the energy blockage in the body is broken and as a result, energy is released. With the balanced distribution of the energy flow to the relevant organs, the healing process is supported, and physical and mental well‐being emerges . Aromatherapy is used in many health fields as well as women's health. Menopause is a process in which physiological, psychological and hormonal changes occur in the life of all women . The World Health Organization defines menopause as "the permanent cessation of menstruation with loss of ovarian activity" . In addition to physical symptoms such as hot flashes, sweating, headache, low libido, fatigue, sleep disorders, palpitations, which occur as a result of the decrease in estrogen and progesterone hormone secretion and its end over time, psychological symptoms such as anxiety, depression and mood disorders are frequently encountered . Due to the increase in the number of women in the menopausal period in the world, it is important to reduce menopausal complaints and improve women's health.Studies have shown that aromatherapy is a complementary method used in a wide variety of situations to reduce physiological and psychological symptoms . It is stated that menopausal symptoms decrease in women who smell lavender aroma during menopause . It is important that the symptoms seen during menopause, which is an important part of a woman's life, are reduced and that women can spend this process more comfortably. While the age at menopause is in the range of 50‐51 years worldwide, it is reported that the age of menopause in our country is between the ages of 47‐49 . From this point of view, women spend about one third of their lives during and after menopause. The trend towards traditional and complementary medicine is increasing day by day in our country. However, in addition to the widespread use of aromatherapy in the world, aromatherapy practices are not common in our country. Diluted and ready‐to‐use forms of aromatic oils are not only available in pharmacies and herbalists, but also a method that people are curious about and want to use. The fact that the cost of ready‐to‐use aromatic oils is cheaper than drugs and easily accessible will provide women with a treatment option in the light of new evidence in line with the conduct of the study. In studies in the literature, it is stated that lavender, rose, geranium, and citrus oils are massaged to women in the menopausal period and provide mental and physical relaxation. Therefore, in our study, the use of Peppermint and Lemon oils to reduce the symptoms of menopausal women and increase their psychosocial well‐being. is planned. Peppermint (Mentha Piperita) oil has analgesic, immune system strengthening, antispasmodic, antipyretic, anti‐nausea and vomiting, anesthetic, helps concentration, increases self‐confidence and creative thoughts, and Lemon (Citrus Lemon) oil is analgesic, immune‐enhancing, antipyretic. It is thought that it can help relieve the psychological and physiological complaints of women in the menopausal period due to its properties such as helping constipation, reducing nausea and vomiting, increasing sleep quality, relieving stress and antidepressant. For this reason, it is planned to use Peppermint and Lemon oils in our study.

Nct (2022). "Mindfulness for African Americans Postpartum." ClinicalTrails.gov.
	This project is a first step to assess a culturally‐tailored Mindfulness Intervention for African Americans Postpartum (MAAP). Elevated perinatal depressive symptoms are more common among disadvantaged African American women (AAW), 40‐60%, compared to the national average,11‐14 and AAW are almost four times as likely to have postpartum posttraumatic stress (13.4% vs 3.5%).15 Further, AAW are twice as likely to have a low birth weight infant (13.2% vs. 7%)16 and 1.6 times more likely to deliver preterm (16.3% vs. 10.2%) compared to non‐Hispanic White women.17 AAW with preterm/low birthweight infants are at increased risk for psycho‐behavioral disturbances and related impairments of infant development. This is a critical public health disparity. The MAAP intervention is culturally adapted for AAW and includes using an AAW interventionist, providing course material that use written and artistic expressions of AAW with illustrations that portray AAW, creation of a community among research participants, inclusion of self‐empowerment strategies, and the use of storytelling that resonates with AAW experience. The Investigators propose a randomized clinical trial to test the MAAP intervention compared to an Educational Program. This study aims to determine the extent to which MAAP affects psycho‐behavioral symptoms and evaluate the effects of MAAP on pro‐ and anti‐inflammatory biomarkers (proinflammatory cytokines and oxytocin). The Investigators will measure stress, depressive symptoms, anxiety, poor sleep, posttraumatic stress, fatigue, pro‐inflammatory cytokines, and oxytocin to determine relationships among these variables and the MAAP intervention versus the Educational Program. The Investigators hypothesize participants in the MAAP intervention will have greater improvement of psycho‐behavioral symptoms compared to participants in the Educational Program. The Investigators also hypothesize women in the MAAP intervention will have a greater decrease in pro‐inflammatory cytokines and a greater increase in oxytocin compared to the Educational Program. The findings of this study will lay the groundwork for future research by identifying best‐practice recruitment strategies, refining measurement strategies, and evaluating feasibility and acceptability. A member of the research team, NICU nurses, and physicians will identify eligible subjects by daily unit census report. Multiple culturally competent strategies will be used to maximize subject recruitment and retention of AAW. The Investigators will be using an AAW interventionist, providing course material that use written and artistic expressions of AAW with illustrations that portray AAW, creation of a community among research participants, inclusion of self‐empowerment strategies, and the use of storytelling that resonates with AAW experience. For recruitment, a NICU healthcare provider will make the first contact with a potential participant and then the PI or perinatal research assistant will further explain the study and informed consent. After informed consent, women will be randomized. The biostatistician will prepare sealed envelopes, using a block size of 4 participants. The MAAPI intervention and the Educational Program have a fixed time of 8 weeks, and will be run continuously allowing for 6 start times per year. Eight weeks will also serve as the recruitment time frame per cohort, estimating cohort size between 3‐5 participants per group. Data will be collected at 3 times for both groups: T1=1st week session; T2= 4th week session; T3 = 8th week (conclusion). T1 will correspond to the first face to face meeting of the MAAP intervention or Educational Program. T1 data will be collected at the beginning of week 1 procedures for both the MAAP group and the Educational Program group. The Investigators estimate an ample recruitment window of 2 months per group will allow assembly of a cohort of at least three participants per group. using this design, the range of time elapsed from birth to a woman's entry into the intervention will v y and will be controlled in the statistical analysis. Women randomized to the MAAP intervention will complete an 8 week (2hr/wk) hybrid adapted Kabat‐ Zinn's MBSR. MAAP intervention includes activities related to spirituality, self‐empowerment, interdependence, and story‐telling, which are salient to AAW. Session topics include 1) Tasting your Life, 2) Seeing and Believing, 3) The scent of Roses, 4) When Life Hurts, 5) Hearing Your Own Cries, 6) Embracing Inner Peace, 7) Holding On, 8) Welcoming Stillness. A manual has been developed for the MAAPI intervention with detailed protocols for each session. Face to face sessions (weeks 1, 4, and8) will be in a quiet room with movable chairs to allow group sitting or free floor space. Sessions for weeks 2, 3, 5, 6, 7 will be virtual classes offered via Zoom. Women will receive practice links and a program work book (5th grade level) containing objectives and weekly MAAP activities. Individual weekly home practice is expected. Type and minutes of home practice will be recorded in weekly logs. Program attendance, type, amount of practice, and changes in mindfulness (Five Facet Mindfulness Questionnaire) will be included in data analysis. Participants randomized to the Educational Program will complete an 8 week (2hr/wk) hybrid educational program matched in duration, frequency, delivery method, and data collection to the MAAP intervention.Like MAAP, it will be delivered using a hybrid format (virtual Zoom and face‐to‐face sessions). Face‐to‐face sessions (weeks 1, 4, & 8) will be in a quiet room with movable chairs to allow group sitting or free floor space. Sessions for weeks 2, 3, 5, 6, 7 will be virtual classes offered via Zoom. At session week 1, participants will set up the Zoom app to ensure capabilities. Session topics are: 1) Perineum and Incision Care, 2) Safe Sexual Practices, 3) Understanding Infant Feeding Methods, 4) How to communicate Effectively with your Child's Health Care Providers, 5) Healthy Eating, 6) Infant Changing and Baths, 7) Infant Safety at Home, and 8) Utilizing Support from Family and the Community. Program content and objectives were reviewed by content experts (Neonatal Nurse Practitioner and Women's Health Nurse Practitioner. Sessions will be given in groups by an African American expert perinatal clinician/educator (not the PI) for all cohorts. Fidelity will be similar to that described for the MAAP intervention. Content will be "set" and delivered consistently across cohorts. Subject receipt will be monitored by attendance. Sessions will not include content on stress reduction (yoga, meditation, etc). Classes will be given in the same setting as the MAAP intervention, at the same time but on a different evening, to avoid crossover (diffusion) of effects. The Investigators will use strategies to maximize retention and decrease missing data. These strategies include: 1) Establish project identity to increase subject engagement with the study. 2) Provide phone calls and texts one day prior to weekly session; on‐going contacts with subjects. 3) Train nurse research assistants in subject retention strategies and subject follow‐up. 4) Women who miss a session (face to face or virtual) will be telephoned to determine reason for absence and address any concerns that may inhibit participation in the project. If the Investigators are unable to reach participants by phone, the Investigators will leave a letter by the infant bedside, and mail a letter to her home address. Participants whose infants have been discharged will have the option of bringing their infants to the face to face sessions and scheduling home visits for data collection of saliva samples and questionnaires at T1, T2, and T3. Recruitment and retention progress and issues will be addressed with the study Mentoring Team and the Data Safety Monitoring Board. Multiple culturally adapted strategies will be used to maximize subject recruitment and retention of AAW. These include mindfulness sessions incorporating the concepts of spirituality, self‐empowerment, and interdepe ence. The MAAP interventionist and the Research Assistant running the Educational Program will both identify as single or multiracial African American or black. Additionally, the MAAP workbook is specific to AAW, including writings and artistic expressions by AAW, and use of images of AAW in meditation/yoga poses. Our research plan already uses some of the recommended recruitment and retention strategies (i.e., compensation and consideration of personal or family medical problem). The study was designed to enroll 40 participants, 20 in the MAAP intervention and 20 in the Education Program. The sample size of 40 was computed based on our primary hypothesis, that the MAAP intervention will have a greater improvement of psycho‐behavioral symptoms, decreased pro‐inflammatory cytokines, and increased oxytocin in African American women with a preterm/low birthweight infant compared to the Educational Program. Based on our pilot and published data, the effect size was estimated at 0.70 for anxiety, 0.45 for prenatal stress and 0.8 for sleep quality, 0.40 for depressive symptoms and 0.36 for proinflammatory cytokines. A sample size of 40 will achieve 80% power, given current effect size estimates per aim. To determine the extent to which the MAAP intervention improves maternal psycho‐behavioral symptoms the Investigators will use growth curve analysis (HLM). HLM model longitudinal data by allowing random effects to account for repeated measures on participants over 3 times, and to evaluate change in trajectories over time. HLMs allow for analysis of unbalanced data across time points, increasing power and reducing bias. HLM analysis will evaluate the effects of the MAAP intervention on change in proinflammatory cytokines and oxytocin levels. Models will control for maternal age and gestational age at delivery.

Nct (2022). "Mindfulness to Reduce Post-cesarean Pain and Prevent Postpartum Depression." ClinicalTrails.gov.
	This clinical trial will test the effect of a mobile mindfulness‐based intervention on reducing post‐cesarean delivery pain and preventing postpartum depression.

Nct (2022). "Mirabegron Combined With Behavioral Intervention for Overactive Bladder：a Prospective Multicenter Randomized Controlled Clinical Study." ClinicalTrails.gov.
	The purpose of this study was to assess the efficacy, safety and tolerability of Mirabegron and behavioral combination versus Mirabegron alone in the treatment of women with overactive bladder (OAB）.

Nct (2022). "Mobility and Voiding Exercises in Older Women With Urinary Incontinence (MoVEonUp)." ClinicalTrails.gov.
	A prospective, two‐arm randomized clinical trial utilizing a multidimensional intervention to reduce falls in older women with Urinary Urge Incontinence. The intervention consist of general balance and strength training, bladder training and urge suppression, and home hazard assessments. The control group will receive informational booklets on fall prevention and behavioral treatment for urinary urge incontinence.

Nct (2022). "Multi-Atlas and Whole Body Radiomics Approaches for Image-Guided Treatment of Gynecologic Cancers." ClinicalTrails.gov.
	This is a grant to conduct correlative science associated with an ongoing NCI‐sponsored multi‐center cooperative group phase 3 trial (NRG‐GY006; NCT02466971). Specifically, this R01 grant pertains to Aims 1.3.7 and 1.3.8 of that trial protocol. The primary objective of the NRG‐GY006 is to test the hypothesis that the addition of triapine to standard chemoradiation with concurrent cisplatin can improve overall survival relative to the standard of care. Patients are randomized 1:1 between the experimental (i.e., triapine) and control (i.e., standard of care) arms. The present R01 grant seeks to investigate the effect of image‐guided intensity modulated radiation therapy (IG‐IMRT) relative to conventional RT on normal tissue toxicity and hematopoietic compensatory response. The investigators will compare 3 methods of delivering external beam radiation therapy: conventional 3D conformal radiotherapy (3DRT), positron emission tomography (PET)‐based IG‐IMRT, and atlas‐based IG‐IMRT. Patients are not randomized between the 3 types of radiation; rather, sites treat using 3DRT as a default, and are required to undergo additional credentialing for IG‐IMRT. Once credentialed for IG‐IMRT, sites are allowed only to treat with IG‐IMRT in order to mitigate selection bias. Patients treated on the trial using IG‐IMRT prior to 5/13/2019 (demarcating the conversion from phase 2 to phase 3) were treated with PET‐based IG‐IMRT. Patients treated on the trial using IG‐IMRT after 5/13/2019 are treated with atlas‐based IG‐IMRT. Thus, there are potentially 6 groups to compare (2 chemotherapy arms and 3 RT modalities). The specific aims of the grant are as follows: Aim 1A: To test the hypothesis that multi‐atlas‐based IGRT reduces acute hematologic toxicity and improves chemotherapy delivery compared to conventional RT Aim 1B: To test the hypothesis that multi‐atlas‐based IGRT results in comparable acute hematologic toxicity and chemotherapy delivery compared to PET‐based IGRT Aim 2A: To test the hypothesis that triapine reduces extra‐pelvic compensatory hematopoiesis relative to therapy with cisplatin only Aim 2B: To test the hypothesis that IGRT (multi‐atlas‐based or PET‐based) increases pelvic compensatory hematopoiesis relative to conventional radiotherapy Aim 3: To develop and validate a radiomics model for gynecologic cancer treatment outcomes that incorporates whole body imaging biomarkers of the inflammatory state and correlates with the effectiveness of triapine.

Nct (2022). "MYPP-trial: myo-inositol Supplementation to Prevent Pregnancy Complications in Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous condition, characterised by metabolic disturbances, insulin resistance and hyperandrogenism. Pregnancies in women with PCOS have an increased risk of gestational diabetes mellitus, preeclampsia and preterm birth, and their offspring have an increased risk of aberrant birth weight and hospitalization. After pregnancy, PCOS is thought to have an impact on breastfeeding success and breastmilk composition. Current strategies to improve pregnancy outcome among women with PCOS have not demonstrated significant risk reduction. Myo‐inositol is a commonly used dietary supplement with a favourable effect on glucose metabolism and insulin sensitivity. Optimal intake of myo‐inositol is associated with a decrease in glucose, lower insulin and lower testosterone levels in women with PCOS. Among women with PCOS‐related disorders (e.g. in women with obesity), myo‐inositol supplementation in pregnancy has been shown to have clinical benefits in preventing adverse pregnancy outcomes in a number of clinical trials, by reducing the risk of gestational diabetes mellitus, hypertensive complications and preterm birth. The MYPP‐trial will be the first randomised prospective trial aimed specifically at pregnant women with PCOS, to evaluate the potential effectiveness of myo‐inositol supplementation as a nutritional intervention to prevent all three pregnancy complications associated with PCOS (i.e. GDM, preeclampsia and preterm birth). Secondary objectives are to evaluate the impact of supplementation on maternal (mental) and neonatal health, breastfeeding practices and breastmilk composition. In addition, a full cost‐effectiveness analysis will be performed. Women with a diagnosis of PCOS and a singleton pregnancy between 8+0 and 16+0 weeks of gestational age are eligible. Participants randomly allocated to the intervention group will receive 4 grams myo‐inositol added to their routinely recommended folic acid supplement, divided over two daily sachets of sugary powder throughout pregnancy. The control group will receive similar looking sachets of supplements containing only the standard dose of folic acid without the added myo‐inositol supplement, as part of the current standard‐of‐care recommendation. In addition to receiving supplements, participants will be asked to complete three questionnaires, provide blood and urine samples once each trimester of pregnancy, and routine ultrasound scanning will be performed to assess fetal growth. All study visits will be aligned with routine antenatal care appointments. Additionally, subjects can choose to participate in research on the impact of myo‐inositol supplementation on breastfeeding and take part in the MYPP biobank. The results of this study will provide important novel recommendations for PCOS patients on the importance of optimising life‐style and nutrient intake to improve pregnancy outcome.

Nct (2022). "Neoadjuvant Chemotherapy Followed by Chemoradiation Versus Chemoradiation for Stage IIIC Cervical Cancer Patients: a Randomized Phase III Trial." ClinicalTrails.gov.
	in this phase III tiral , stage IIIC cervical cancer patients with carcinoma >4 cm in greatest dimension and/or lymph node >2cm in short axis will be randomly assigned to two circles of NAC with albumin‐bound paclitaxel and carboplatin followed by standard CRT with weekly cisplatin plus pelvic radiotherapy or to standard CRT alone. The primary end point was 3‐year progression‐free survival (PFS). Secondary end points were response rate, 3‐year locoregional control, 3‐year overall survival (OS), safety, and quality of life.

Nct (2022). "Nerve Stimulation Using a TENS to Provide Pain Relief During Surgery for Overactive Bladder." ClinicalTrails.gov.
	This will be a double blind randomized control trial in men and women with urinary urge incontinence that are undergoing outpatient operative cystoscopy for Onabotulinumtoxin A chemo denervation as third line therapy for overactive bladder (OAB) or urinary urge incontinence (UUI). Subjects will be identified by the University of Rochester Urologists and Urogynecologists participating in the study who currently oversee urinary urge incontinence care. Subjects will be randomized into two groups. One group will be undergoing the cystoscopy with transcutaneous electrical nerve stimulation (TENS) for analgesia and the second group will have cystoscopy with placebo TENS.

Nct (2022). "New Cross-linked Hyaluronan Gel to Prevent Adhesion After USG-MVA: RCT." ClinicalTrails.gov.
	There is limited data to evaluate the incidence of IUA after using this NCH gel in patients undergoing surgical evacuation via USG‐MVA for the treatment of first‐trimester miscarriage. Previous RCT showed a significant reduction in IUA with the use of NCH gel, with IUA detected in only 9.5% of patients with NCH gel applied compared to 24.1% in the control group. However, the group did not involve patients undergoing surgical evacuation by USG‐MVA. Therefore, the objective of this prospective, randomized controlled study was to evaluate the effectiveness of this NCH gel in the prevention of IUA development as assessed by hysteroscopy after USG‐MVA, in the treatment of first‐trimester miscarriage.

Nct (2022). "Nifedipine Plus Magnesium Sulfate Versus Magnesium Sulfate for Very Early Preterm Tocolysifs." ClinicalTrails.gov.
	Objective: This trial is designed to compare between the effectiveness of nifedipine plus magnesium sulfate (MgSO4) and MgSO4 alone for tocolysis in women with threatened preterm labor. Patient Population: The population will include pregnant women at gestational age between 28 and 31 weeks who are 18 years old or older and have signs of threatened preterm labor. Study Design: This is a single‐center, prospective, randomized controlled clinical trial. A total of 264 women pregnant between 28 and 31 weeks having threatened preterm labor will be enrolled and randomized into two parallel treatment arms. Patients in the group A will receive nifedipine plus MgSO4, while patients in group B will MgSO4 only. Treatment: All patients will be randomized on the day of enrollment. Patients with threatened preterm labor will receive the respective tocolysis in each group. All patients will receive corticosteroids for lung maturity according to the local protocol. Primary outcome: Number of women not delivered within 48 hours of starting tocolytic therapy. Secondary outcomes: perinatal mortality, a composite of adverse neonatal outcomes, birth weight, days on ventilation support, length of admission in neonatal intensive care, prolongation of pregnancy more than 7 days, delivery after 37 weeks of gestation, number of days till delivery, maternal mortality, maternal infection, and harm to mother from intervention.

Nct (2022). "Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer." ClinicalTrails.gov.
	Patients with adenocarcinoma or squamous cell carcinoma of the cervix, FIGO Stage IB2‐IB3 node positive or Stage IIB‐IVA will be randomized to conventional cisplatin‐based chemo‐radiation or to 4 cycles of induction immunotherapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks, followed by cisplatin chemo‐radiation with concurrent nivolumab 240mg every 2 weeks. Primary outcome will be 3‐year progression‐free survival.

Nct (2022). "NO3-rich Beet Juice and Exercise on Postmenopausal Women Cardiovascular Health." ClinicalTrails.gov.
	In the context of physical exercise, there is no evidence of the acute and continued use of beetroot juice with a previously recommended dose of nitrate (NO3) (>300mg) on the cardiovascular performance of hypertensive and postmenopausal women. We will investigate the effects of beetroot juice rich in NO3 acutely (first day: 140mL/800mg) and during a week with daily doses (second to the seventh day: 70mL/400mg) on blood pressure, heart rate (HR), cardiac autonomic control, EF, inflammatory, hormonal, and stress biomarkers oxidative stress and enzymes involved in nitric oxide synthesis and mitochondrial regulation, under resting conditions, as well as mediated by submaximal aerobic exercise sessions. Through a randomized, crossover, triple‐blind, placebo‐controlled clinical trial, 25 physically inactive hypertensive women will undergo an acute and 7‐day trial, each with two intervention protocols: 1) placebo and 2) beetroot; in which will ingest beet juice with or without NO3 in its composition with a 7‐day washout interval. On collection days, exercise will be performed on a treadmill for 40 minutes at a speed corresponding to 65‐70% of VO2peak. The collection of variables (cardiovascular, autonomic, and blood samples for molecular analyses) of the study will take place at rest (120 minutes after ingestion of the intervention), during exercise (40 minutes), and in the effort recovery stage (during 65 minutes) based on previously validated protocols. The collections were arranged so that the measurement of one variable does not interfere with the other and that they have adequate intervals between them.

Nct (2022). "ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer." ClinicalTrails.gov.
	The purpose of this Phase 2 study is to compare two doses of ONC‐392 in combination with a fixed dose of pembrolizumab in participants with ovarian cancer who are resistant to platinum‐based chemotherapy and have disease progression on line of therapy containing bevacizumab. Results from this study will be used to inform the study design, patient population, and dose selection for future studies in advanced ovarian cancer.

Nct (2022). "Optimized Acupuncture Treatment for Female Stress Urinary Incontinence." ClinicalTrails.gov.
	Stress urinary incontinence (SUI) mainly refers to the involuntary leakage of urine when abdominal pressure increases, such as sneezing, coughing, laughing or exercise. According to epidemiological studies, the global median prevalence of female urinary incontinence is 27.6% (4.8%‐58.4%), of which SUI accounts for more than 50%. Previous study have demonstrated that acupuncture intervention can reduce the urine leakage in pad test, decrease the ICIQ‐SF score, so as to help the patients alleviate the symptoms and improve their quality of life. This multicenter randomized controlled trial set 3 groups. Patients will receive 3 different applications of acupoint combinations so that the optimization of acupuncture treatment of female SUI will be find.

Nct (2022). "Oregovomab Plus Chemotherapy in Neo-adjuvant Setting in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer." ClinicalTrails.gov.
	Phase 2, double‐blind, placebo‐controlled, multi‐center study to compare the efficacy and safety of five administrations of oregovomab 2 mg IV versus placebo, infused in a schedule dependent sequence with specific cycles of a standard six‐cycle chemotherapy regimen (paclitaxel and carboplatin), for the treatment of patients with newly diagnosed advanced ovarian cancer who are planned to receive neoadjuvant treatment. Patients will receive oregovomab or placebo at Cycles 1 and 3 in combination with paclitaxel and carboplatin prior to IDS, followed by oregovomab or placebo at Cycles 4 and 6 in combination with paclitaxel and carboplatin, and oregovomab or placebo monotherapy at Cycle 6 plus 12 weeks. This study will screen approximately 96 patients to randomize approximately 88 patients. All eligible patients will be stratified by FIGO Stage (Stages IIIA, IIIB versus Stages IIIC, IV). The study includes screening period, treatment period, post‐treatment follow up, safety follow and long term follow up.

Nct (2022). "Outpatient Antibiotics Following Previable Rupture of Membranes (pPPROM) Between 18 0/7 and 22 6/7 Weeks Gestational Age." ClinicalTrails.gov.
	A randomized, controlled, non‐placebo trial to primarily assess the effect of oral, outpatient antibiotics (i.e., azithromycin and amoxicillin) on latency (i.e., proportion of patients that deliver within 28 days from membrane rupture) following previable, prelabor rupture of membranes between 18 0/7 and 22 6/7 weeks gestational age.

Nct (2022). "PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer." ClinicalTrails.gov.
	This is an international, multicenter and randomized open‐label phase III study designed to demonstrate, in patients with stage IIIC1 cervical cancer, whether para‐aortic lymphadenectomy followed by tailored chemoradiation is associated with increased disease‐free survival compared to patients staged with FDG‐PET/CT only followed by chemoradiation. The planned sample size is 510; including 200 patients in France. In this trial, patients will be assigned in one of the two following treatments arms: Arm A (control arm): Standard chemo‐radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations. Arm B (experimental arm): Pretherapeutic para‐aortic lymphadenectomy followed by tailored chemo‐radiotherapy and brachytherapy. Each patient will be followed up for 5 years.

Nct (2022). "Patient Blood Mangement (PBM) Using IV Iron in Patients With Gynecologic Cancer." ClinicalTrails.gov.
	To demonstrate the safety and effectiveness of a patient blood management program in gynecological cancer patients undergoing surgery, radiation therapy, and chemotherapy, and to establish a patient blood management program and introduce it as a standard treatment.

Nct (2022). "Patient Reported Outcomes Following Interventional Procedures in Pelvic Pain." ClinicalTrails.gov.
	The aim of this study is toillustrate whether pulsed radiofrequency treatment is safe and effective intreating the chronic perineal pain associated with PN or pudendal nerve compression; and whether it can be used as an integral part of its multidisciplinary managementBased on literature, the prevalence of Chronic Pelvic Pain (CPP) in general population ranges between 5.7% and 26.6%(Ahangari, 2014). There are many countries and regions with no published data in the field of CPP (Ahangari, 2014). CPP is a great burden to the patients and the healthcare systems (Latthe et al., 2006). About £154 million was the estimated cost of treatment for the women who suffer from CPP per year (Cheong and William Stones, 2006). CPP affects one's movement and their posture due to the secondary hyperalgesia in the pelvic muscles leading to diminished proprioception. About 50%‐ 70% of women with CPP have limitation on their daily activity(Ahangari, 2014). PN occurs in men, but the incidence/prevalence is not well studied. The principle therapy for chronic neuropathic pain is to eliminate the underlying causes of the pain (Belgrade, 2003), for PN this may involve surgical decompression. Pharmacotherapy and physiotherapy are two different options for treatment of neuropathic pain but they each come with limitations and drawbacks. Different techniques for pudendal nerve block have been described for managing PN but they have complications that may be serious such, vascular injury or intravascular injection with toxicity. The indication of surgery is in patients with failure of conservative treatment or other PNB techniques / modalities and includes decompression or neuromodulation. Type of the study: A retrospective randomized controlled study Study Setting: University college London hospital Sample Size Calculation: Sample size calculation was carried out using G*Power 3 software (Faul et al., 2007). A calculated minimum sample of the cases is 60 patients, 30 in each group. Study tools (in detail, e.g., lab methods, instruments, steps, chemicals, …): Total number of the cases is 60 patients, 30 in each group. Intervention(s): 1. Informed written consent: ‐ A copy of the signed Informed Consent form will be given to the participant. The original signed form will be retained at the study site and a copy placed in the medical notes. 2. The patient is placed in the prone position 3. The ischial spine is then located using fluoroscopic X ray. 4. Aseptic cleaning of the skin in the target area 5. Patient will randomly be allocated to the control group receiving steroid and local anaesthetic injection or treatment group receiving pulsed radiofrequency treatment and local anaesthetic. Randomisation will be performed using sealed envelopes. I. Local anaesthetic and corticosteroid injection (control group) ▪ Under X‐Ray guidance, the Needle (22G 5‐10 cm insulated radiofrequency needle) is advanced perpendicular to the skin and placed transgluteally, directly avoiding the adjacent sciatic nerve at either the extremity of the ischial spine between the sacrotuberous and sacrospinous ligaments. ‐ Sensory Electrostimulationis used to identify the nerve. For the motor stimulation, a unilateral contraction of the anal sphincter indicates that the inferior anal nerve had been stimulated while for the sensory stimulation, a sensation of tingling or numbness in the perineal region may be felt by the patient. ‐ Contrast injected to avoid intravascular injection. A blinded operator sets the radiofrequency machine for a timer alert at five minutes. ‐ After confirming the exact location of the needle tip, 4 mL of 1% lidocaine and 3.3 of dexamethasone in 1 mL are injected. II. Pulsed radiofrequency (Treatment/intervention group) ‐ Needle is placed using the same technique as above and contrast medium is injected. ‐ Lesion: ‐ Radiofrequency current will be applied for 5 minutes, 120 ms, at 2 Hz, with maximum tissue temperature increased to 42°C. (usually not felt by the patient) ‐ 4 mL of 1% lidocaine and 1 mL of NaCl .9% are inject . 6. Post procedure instructions:‐ ▪ Standard post procedure monitoring for 1 hour in theatre recovery, including treatment of nausea/vomiting and localized pain with standard intravenous/oral medication. ‐ Immediate adverse events reporting. ‐ Standard hospital post procedure instructions Research outcome measures: 1. Primary Endpoint: Reduction in at least 1.5 point pain as measured by Numerical Rating Scale Secondary Endpoint A. NRS at 0, 1 and 12 weeks B Quality of Life Assessment at baseline, week 1, week 6 and week 12 a. EDQ5‐5L b. SF‐12 c. Brief Pain Inventory d. Global response Assessment C. Mood assessment at baseline, week 6 and week 12 a. Pain Catastrophising Questionnaire b. Beck Depression Inventory II c. Hamilton Anxiety Rating Scale d. Sexual function assessment (questionnaire) at baseline, weeks 6 and 12 e. Lower urinary tract symptom assessment at baseline, weeks 6 and 12 f. Bristol Female Lower Urinary Tract Symptoms (BFLUTS‐SF) g Review of pain medication use at weeks 6, 12 compared to baseline. h. Assessment of all patients against Nantes criteria at baseline 2.5‐Data management and analysis (Details needed): Data collection. Telephone review ‐ Week 1 1. Telephone review in 1 week to assess for complication and side effcte profile. 2. Global pelvic pain NRS scores over telephone. 3. Adverse events reporting. b. Telephone review at 6 weeks and 12 weeks 1. review pelvic pain 2. Questionaires: global pelvic pain, QoL and function 3. Medication review 1. S ‐ Study/Statistical design (e.g. randomised controlled trial, case control study, pilot study): 2. Prospective 3. Parallel group ( 2 different groups) 4. No active Control 5. Randomized 6. Single blinded 7. multicentric study (at UCLH center) Statistical methods: i. All data will be collected and cleaned by Excel program then will be analyzed with SPSS software (Statistical Package for the Social Sciences, version 16, SSPS Inc, and Chicago, USA). ii. Continuous parametric data between two groups, two sample T test will be used. iii. Continuous parametric data between more than 2 groups, ANOVA test will be used. iv. Descriptive statistics will be done in the form of mean and standard error (SE). v. Frequency of qualitative variables and Chi‐square test will be done. vi. In Categorical data, Chi‐squared test will be used.

Nct (2022). "Pelvic Floor Muscle Training in Female CrossFit and Functional Fitness Exercisers." ClinicalTrails.gov.
	BACKGROUND: Physical activity and exercise have well‐known beneficial effects on several physical and psychological health outcomes. However, it has been proposed that regular participation in physical activity and exercise may lead to greater risk of developing pelvic floor dysfunctions (PFD) in women. The pelvic floor consists of muscles, fascia and ligaments and forms a hammock‐like support at the base of the abdomino‐pelvic cavity. The function of the pelvic floor is to provide support to the pelvic organs (the bladder, urethra, vagina, uterus and rectum) and to counteract all increases in intra‐abdominal pressure and ground reactions forces during daily activities. Additionally, the pelvic floor facilitates intercourse, vaginal birth, storage of stool and urine and voluntary defecation and urination. A dysfunctional pelvic floor can lead to urinary and anal incontinence, pelvic organ prolapse, sexual problems and chronic pain syndromes. UI is the most common PFD, defined as "the complaint of involuntary loss of urine". SUI, urgency urinary incontinence (UUI) and mixed urinary incontinence (MUI) are common subtypes of UI. In women, SUI accounts for approximately half of all incontinence types and is defined as "the complaint of involuntary loss of urine on effort or physical exertion (e.g. sporting activities), or on sneezing or coughing". UUI is defined as the "complaint of involuntary loss of urine associated with urgency" and MUI as "complaints of both stress and urgency urinary incontinence". High prevalence rates of UI among both parous and nulliparous female athletes and exercisers have been reported in several cross‐sectional studies. The prevalence rates varies between 0‐80% with the highest prevalence found in high impact sports such as trampoline jumping, gymnastics and strengths sports with high increases in intraabdominal pressure (e.g. powerlifting). CrossFit and functional fitness, which are trending exercise forms, includes a combination of heavy lifting and high impact activities at high intensities. High prevalence of UI among CrossFit/functional fitness exercisers has been reported in several recent cross‐sectional studies, ranging from 41‐84%. Leakage during sport and exercise may affect performance and cause bother, frustration and embarrassment, and may further lead to avoidance or cessation of sport and exercise. To date, there is level 1 evidence and grade A recommendation for PFM training alone to be first line treatment for SUI, MUI and pelvic organ prolapse in the general female population. In addition, PFM training is highly effective as primary prevention; pregnant continent women who exercise the PFM are at 62% less risk of UI in late pregnancy and 29% less risk of UI 3‐6 months postpartum. Evidence of the effect of PFM training in athletes or strenuous exercisers is sparse. In one study on female soldiers and two small case series in female athletes and exercisers, PFM training led to reduced symptoms of UI. However, none of these studies included a non‐treated control group and the internal validity is therefore low. To our knowledge, only one RCT has assessed effects of PFM training on SUI in athletes. Female volleyball players (n=16) who followed a PFM training program had significant improvements of SUI compared to a control group (n=16). Based on today's knowledge we do not know whether PFM training is effective in strenuous exposed to excessive impact and increases in intraabdominal pressure during CrossFit‐ and functional fitness activities. Given the high impact on the pelvic floor in these exercisers, it is presumed that they need much better pelvic floor muscle function than non‐exercisers. On the other hand, these exercisers may be motivated for regular training. Strength training of the PFM, if proven effective, may be easily incorporated in their basic training regimens both as prevention and treatment strategies of SUI. AIMS: The aim of this RCT is to assess the effect of PFM training on symptoms, bother and amount of SUI among female CrossFit nd functional fitness exercisers. STUDY DESIGN AND METHODS: To recruit participants, we will contact CrossFit boxes and functional fitness clubs in or near Oslo. Social media platforms (such as Facebook, Instagram) will also be used. The study is an assessor‐blinded RCT evaluating the effect of PFM training on SUI in CrossFit and functional fitness exercisers. At baseline, a pelvic floor muscle assessment (resting pressure, strength and endurance) will be performed of all participants. In addition, the participants will respond to an electronic questionnaire, measuring self‐reported symptoms of UI and bother. The participants will be randomly assigned to either a PFM training group (EG) or a control group (CG) with no intervention. The intervention consists of a daily home‐based PFM training program with weekly follow‐up by a physiotherapist. After a 16‐week intervention period, all participants will perform a post‐test including the same previous mentioned outcome measures.

Nct (2022). "Pembrolizumab With Chemotherapy and MK-4830 for Treating Participants With Ovarian Cancer (MK-4830-002)." ClinicalTrails.gov.
	The primary objective is to evaluate in participants with high‐grade serous ovarian cancer (HGSOC), whether the reduction from baseline in circulating tumor DNA (ctDNA) at Cycle 3 (ΔctDNA) is larger in participants receiving MK‐4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy.

Nct (2022). "Perineal Massage and Pelvic Floor Exercise in the Antenatal Period." ClinicalTrails.gov.
	The research was conducted as a randomized controlled trial. The simple randomization method will be used for the assignment to groups. The data of the research; will be collected using the Preliminary Evaluation Form, Personal Information Form, Female Sexual Function Index, The International Consultation on Incontinence Questionnaire‐ICIQ‐SF (Turkish Version), and Fecal Incontinence Severity Index. The research will start at the 34th week of pregnancy and the questionnaires will be administered in the 3rd month after delivery. There will be 3 groups in the research.An active control group will be formed as the control group. The control group will be given the "Pelvic Floor Dysfunction Prevention Training" booklet prepared by the researchers. Experimental 1 group will receive perineal massage training in addition to the "Pelvic Floor Dysfunction Prevention Training" booklet given to the control group. Experimental 2 group will receive pelvic floor exercises in addition to perineal massage training and the "Pelvic Floor Dysfunction Prevention Training" booklet given to the control group.

Nct (2022). "PErsonalized TReatment for Endometrial Carcinoma." ClinicalTrails.gov.
	Endometrial carcinomas can be classified into four molecular subgroups, i.e. mismatch repair deficient (MMR‐D), p53 abnormal (p53 abn), polymerase‐ϵ (POLE) ultramutated, and "no specific molecular profile" (NSMP). Molecular subgroups can be considered to be distinct diseases as they are associated with different clinicopathologic characteristics, prognoses and, possibly, responses to adjuvant therapy. Molecular classification of endometrial carcinoma is recommended to be implemented in routine clinical practice to improve prognostication and triage to adjuvant therapy. The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial, led by the Finnish Gynecologic Oncology Group (FINGOG), is a multicenter prospective clinical trial for women with stage I‐II molecular integrated high‐intermediate or high‐risk endometrial carcinoma. The efficacy of chemotherapy vs. chemoradiotherapy is compared in p53 abn subtype and nonendometrioid carcinomas, and vaginal brachytherapy vs. whole pelvic radiotherapy in MMR‐D and NSMP molecular subgroups. Patients who consent to follow‐up within the trial but not to randomization are treated as recommended in multidisciplinary meetings and enrolled for follow‐up only (comprehensive cohort study design). The primary outcome is the 5‐year cumulative incidence of disease recurrence. Secondary outcomes are vaginal, pelvic, and distant recurrence rates, 5‐year recurrence‐free and overall survival, adverse events, and patient‐reported symptoms and quality of life. The findings of the trial may eventually help decrease under‐ and overtreatment and, consequently, improve patient outcome and decrease treatment‐associated adverse effects.

Nct (2022). "A Phase 2, Randomized, Placebo-controlled, Double-blind Study of EG017 in Female Patients With Stress Urinary Incontinence." ClinicalTrails.gov.
	The main purpose of this study is to assess the efficacy of EG017 in female patients with stress urinary incontinence (SUI) compared with placebo as measured by the percent change in the urinary incontinence volume measured in a 1‐hour pad test from baseline at week 12.

Nct (2022). "A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy." ClinicalTrails.gov.
	This is a multicenter, randomized, open label study including patients with advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) HRDpositive high‐grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking. The main scope of the trial is to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib. Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B). Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm independent of LOH or LOHhigh/ BRCAwt, FIGO stage III vs. IV, and countries. In both of the arms, tumor assessments (CT or MRI) will be performed 9‐12 weeks after the start of therapy (after 3rd cycle of chemotherapy), after another 9‐12 weeks (during maintenance therapy in Arm A and after the 6th cycle of chemotherapy in Arm B) and every 6 months thereafter. The tumor marker CA‐125 will be assessed every 12 weeks in both arms. During chemotherapy treatment, clinical visits (blood cell counts, detection of toxicity) occur at least every 3 weeks (depending on the chemotherapy regimen). Serum pregnancy tests for WOCBP occur at least every 4 weeks. During maintenance therapy with niraparib, clinical visits (blood cell counts, detection of toxicity) occur every 4 weeks for the first 11 months and every 12 weeks thereafter. Serum pregnancy tests for WOCBP occur at least every 4 weeks. Complete physical examinations will take place every 12 weeks. Safety will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs). About 60 sites in 5 European countries will participate in this study to recruit 640 patients in 36 months.

Nct (2022). "Photobiomodulation in Post Menopause Genitourinary Syndrome." ClinicalTrails.gov.
	The goal of this project is to evaluate the clinical response of patients with symptoms of genitourinary menopause syndrome after the application of photobiomodulation in the vagina and its introit. METHOD: In this randomized, double‐blind, placebo‐controlled study protocol, women over 50 years of age who are in the postmenopausal period (amenorrhea for at least 12 months, with no pathology involved) with one or more symptoms of PGS will be selected. Participants included in the study will be randomly divided into two groups: group A, which will receive photobiomodulation with a vaginal diode laser and its introit and group B (placebo) with the laser device turned off. Both treatments will be maintained for 4 consecutive weeks.The treatment group (n=30) will receive four consecutive applications, using laser diode DMC (808 nm), 4J per point, 100mW of power, 510mW/cm², beam area of 0.2cm², 8 sites in the external vagina, for the 40s in each site, once per week for 4 weeks. The Placebo Group (n=30) will be handled as treated, but with the laser turned off. Quality of life will be analyzed using the female sexual functioning index (FSFI‐6), the urinary incontinence questionnaire (ICIQ‐SF), the intensity of menopausal symptoms will be evaluated using a visual analogue scale (VAS), the vulvo vaginal atrophy will be measured by the Vaginal Health Index (VHI) and compared between groups. Also, the vaginal temperature will be measured using a thermal camera, as well as the pressure of the pelvic floor force (vaginal dynamometer) and a 1‐hour Pad Test will be performed to quantify the urinary loss. The data will be tested for normality using the Shapiro Wilks test and, if they present a parametric distribution, they will be represented by means of their respective means and standard deviations.

Nct (2022). "Physical Exam Indicated Cerclage in Singleton Gestation 24 Weeks to 25 Weeks and 6 Days Gestation." ClinicalTrails.gov.
	RCT assessing preterm delivery rate in singleton pregnancies having a physical‐exam indicated cerclage placed between 24 weeks and 25 weeks and 6 days. Patients randomized to either cerclage intervention or routine standard of care (no cerclage).

Nct (2022). "PhytoSERM to Prevent Menopause Associated Decline in Brain Metabolism and Cognition." ClinicalTrails.gov.
	This is a double‐blinded, randomized, placebo‐controlled, parallel designed, proof‐of‐concept phase 2 clinical trial to determine effect of PhytoSERM in regional brain metabolism, cognition and vasomotor symptoms in menopausal women. PhytoSERM or placebo pills will be administered orally once a week over 24 weeks. Safety and tolerability will also be assessed over the duration of the study. To determine eligibility, all participants will undergo cognitive assessment, physical and neurological examination, imaging scans, electrocardiogram (ECG), clinical/safety laboratory assessment, and interviews. After a 2‐4‐week screening period, participants will be randomized to study intervention (PhytoSERM 50mg administered orally, once per day) or matching placebo, in a 1:1 allocation. Brain imaging to evaluate the primary endpoint (standardized uptake value ratio (SUVR) by FDG‐PET) will be conducted at screening and 24 weeks (6 months). Study participants will be asked to complete a total of 7 study visits. All participants will be enrolled at a single site, at the Alzheimer's Prevention Program (APP) at Weill Cornell Medical Centre (WCMC, New York). This study protocol will include an embedded single‐dose, 24‐hour pharmacokinetic (PK) study in a subset of 12 participants which will begin after the first dose of the study intervention.

Nct (2022). "Plasma Rich in Growth Factors (PRGF) for the Treatment of Lichen Sclerosus Atrophicus of the Vulva." ClinicalTrails.gov.
	Lichen sclerosus is a chronic dermatosis of the skin and semimucous membranes, characterized by the presence of well‐defined atrophic white papules or plaques, which appear mainly on the skin of the anogenital region of both sexes, and less frequently on the skin of the trunk. , mainly affecting postmenopausal women. There is no absolutely effective treatment. Only potent topical corticosteroids control symptoms and improve outcomes, although prolonged use can increase skin atrophy. In severe vulvar lesions, 0.05% clobetasol propionate is indicated, followed by a less potent topical corticosteroid. Relapses often occur if treatment is discontinued altogether, but respond well to reintroduction of treatment. Plasma Rich in Growth Factors (PRGF®) is a mixture of autologous proteins, prepared from a certain volume of platelet‐rich plasma obtained from a small volume of blood, which does not contain leukocytes. To date, there have been no studies evaluating PRGF® treatment in vulvar lichen sclerosus. However, there are several publications that assess the efficacy of PRPs as a treatment for vulvar lichen sclerosus. This clinical study has been designed with the aim of evaluating the efficacy of PRGF® in reducing the main symptoms of vaginal lichen sclerosus atrophicus.

Nct (2022). "Post Isometric Relaxation and Core Stability Exercises in Sacroiliac Joint Dysfunction." ClinicalTrails.gov.
	A previous study conducted by Farhadi et al. assessed that the prevalence of sacroiliac joint pain has been reported between 13‐30% in postpartum females aged between 40‐and 45 years. Specifically, 13% of the individuals with low back pain have the origin of their pain from the sacroiliac joint. It has been found that 33.6% of pregnant women have pelvic girdle pain, and 18.9% of post‐partum women have "serious" pelvic girdle pain. In most women with pregnancy‐related sacroiliac, joint pain resolves with time after pregnancy, but in some females, the pain lingers on. Patients with Sacroiliac dysfunction generally complain of pain in their back, and buttock or may radiate to the knee. On examination, there is pain and local tenderness. The symptoms increase on position change such as getting up from a sitting or lying position or while ascending and descending stairs. Sacroiliac pain is localized to the posterior pelvis and is described as stabbing pain deep. Terzi and Clinton et al., (2019) found thirty women diagnosed with post‐partum SIJ pain, their age ranged from (25‐35)years, their BMI ranged from (25‐to 30)kg/m², and their number of parity ranged(from 2‐to 4)times were selected randomly from the outpatient clinic of Al‐Ahrar teaching hospital. Women were divided randomly into two equal groups, Group A (Control group): 15 patients, they were treated by TENS for 4 weeks 30 min\session, 3 sessions \week. Group B(Study group):15 patient, were treated with core stability exercises for 4 weeks, 30 min\session, 5 sessions \week plus TENS as for group A. All participant was evaluated by VAS, Oswestry disability index (ODI), serum cortisol levels before and after treatment. The results revealed that there was a statistically significant decrease in the mean value of VAS in the group (B) when compared with its corresponding value in group (A). In spite of there being no statistically significant difference in plasma cortisol level, there was a clinical difference and high percent of improvement in favor of group B (8.83%) over group A (2.66%). Also, there was a statistically significant decrease in the mean value of ODI in the group (B) when compared with its corresponding value in group (A). It was concluded that core stability exercises could be used as a complementary treatment in reducing post‐partum SIJ pain. Also, it could be considered a useful treatment to increase flexibility and range of motion. Shamsi et al., in 2014, found that reduced pain and increased function are outcomes when core stability exercises are used in the early stages of interventions. Also, Huxel et al., found that core exercises resulted in better outcomes measures than general exercise in the first 3 months of interventions for LBP, as they found clinical improvements in pain perception and functional disability levels when the patients with LBP engaged in core‐specific exercise. One study was done by Noelle M.Selkow et al., (2017) supports the findings of our study by concluding that MET is effective in decreasing pain in patients with acute low back pain. Another study was done by Roberts BL where he described two techniques of soft tissue manipulation viz neuromuscular technique and MET and found that MET can reduce Pain, muscle rigidity, and lengthen muscle fibers. The effect of MET on disability is supported by Fenech et al., (2015) determined that LBP is one of the most common musculoskeletal problems that affects about 60‐80% of the population throughout their life expectancy. The lifetime prevalence of low back pain is reported to be 84% with 11‐12% of the population being disabled by this condition. In 2010 Global Burden of Disease conducted a study on low back pain and estimated the global age‐standardized point prevalence to be 9.4%. Low back pain is a self‐limiting condition that can commonly be found in middle age ranging from 35 to 65 years and 90% of the people can be cured within 3‐4 months without any treatment protocol.

Nct (2022). "Postoperative Return to Sexual Activity." ClinicalTrails.gov.
	The investigators will conduct a randomized controlled trial comparing standardized counselling to routine counseling regarding return to sexual activity using a previously developed structured counselling instrument. Adult women (age ≥18 years) who are undergoing reconstructive surgery for pelvic organ prolapse and / or urinary incontinence who report that they are currently sexually active (as defined by their own assessment of the meaning of this question) will be eligible to participate and recruited during their preoperative visit. The recruitment will take place across 10 sites in Canada and the Unites States. The hypothesis is that use of a newly developed standardized counselling intervention regarding resumption of sexual activity will result in improved preparedness to return to sexual function compared to routine care. The primary outcome will be preparedness at 2‐6 months postoperatively. Preparedness for return to sexual activity will be measured by modifying the Patient Preparedness Questionnaire, Question #11: "Overall, I feel prepared for my upcoming surgery" to make it relevant to sexual activity following surgery. The investigators will consider women prepared if they answer "strongly agree" on a 6‐point Likert scale from "strongly agree" to "strongly disagree" to the modified statement: "Overall, I feel prepared for resuming sexual activity after my surgery". In addition to the primary outcome, the investigators will compare the secondary outcomes of sexual function, time to return to sexual activity, and postoperative pain with sexual activity. Sexual function will be measured by Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA‐Revised (PISQ‐IR) score. Pain with sexual activity will be assessed by response to question 11 on PISQ‐IR: "How often do you feel pain during sexual intercourse?" Women who have already consented for surgery for pelvic organ prolapse surgery will be approached to offer participation in the study at the pre‐operative visit. After enrollment in the study, women will complete demographic information, undergo a pelvic organ prolapse quantification examination, and complete the PISQ IR and the Pelvic Floor Distress Inventory ‐ 20 (PFDI‐20). Women will then be randomized to either usual or scripted counseling for resumption of sexual activity. The randomization assignment will occur as close to the intervention as possible, i.e. the night before, or the morning of, scheduled 6‐8 week postoperative appointment. The randomization schema will be generated using an online randomization table with alternating blocks of 4 and 6. If randomized to the treatment group, patients will be counselled using the structured counselling instrument, and given a bulleted list of the counseling instrument to take home with them. After the visit, women will complete the PFDI‐20 and Preparedness question in telephone‐administered, paper or online questionnaire format. The study team will contact each participant by telephone or electronically at 1 month intervals starting at 2 months after surgery, to ascertain whether they had returned to sexual activity. If the postoperative visit occurred at 8 weeks, the first contact will occur at 3 months. If the patient has returned to sexual activity, again defined by the patient's own interpretation of the question about return to sexual activity, then women will be asked to complete the PISQ‐IR and Preparedness question by telephone‐administered, mailed paper, or online questionnaire format. No further followup will be required after return to sexual activity. If women are not yet returned to sexual activity, they will be contacted at 1 month intervals, to a maximum interval of 6 months after surgery, to determine return to sexual activity and timing of administration of the PISQ‐IR and Preparedness question. If a woman has not yet returned to sexual activity by 6 months, we will administer the PISQ‐IR and Preparedness question by telephone‐administered, mailed paper, or online questionnaire format.

Nct (2022). "A Practice-Based Intervention To Improve Care for a Diverse Population Of Women With Urinary Incontinence." ClinicalTrails.gov.
	The burden of urinary incontinence (UI) on American women is immense in human and financial terms, and continues to rise with the growing population of older adults. The goal of this proposal is to improve the care for UI provided to women and, in doing so, decrease the utilization of specialty care while improving patient outcomes. Specific Aim 1 seeks to improve the quality of incontinence care provided to an ethnically diverse population of women through a controlled practice‐based intervention involving primary care providers. The intervention involves the implementation of PCOR measures. Four Southern California medical groups will participate in a cluster randomized controlled trial in which 60 offices (15 per site) will be randomized to undergo a practice‐based incontinence intervention led by a "clinical champion dyad" comprised of a primary care provider and urologist/urogynecologist, both of whom are members of that specific medical group. The intervention will include physician education, individual performance feedback, electronic decision support, patient education using dedicated advanced practice providers (APPs), and the implementation of an electronic referral service. The quality of patient care, as evidenced by compliance with primary care UI quality indicators the investigators developed and pilot‐tested, will be measured across the two randomized arms after implementation of the intervention. Compliance with these quality indicators will be the key means to implement PCOR evidence, while, at the same time, measure quality. In Specific Aim 2, utilization of specialists will be compared before and after the intervention. The investigators hypothesize that improved care at the level of the primary care physician will reduce the number of specialty referrals. Specific Aim 3 will seek to measure the effect of the intervention on patient outcomes. Under the hypothesis that a practice‐based intervention will improve disease‐specific outcomes, symptom severity, quality of life, and patient knowledge will be measured at baseline using validated questionnaires. After implementation of the intervention, these questionnaires will be given a second time six months later and outcomes will be compared between control and intervention groups. The investigators expect that this intervention will also reduce disparities in care for underrepresented minorities.

Nct (2022). "Premenstrual Symptoms and Aromatherapy." ClinicalTrails.gov.
	Premenstrual syndrome is a health problem characterized by mitigation of symptoms in several days after the beginning of menstruals, or after the beginning of menstruals, which occurs in the Luteal phase of menstrual cycle in the luteal phase . About 80‐95% of women complained of premenstrual syndrome complaints. This ratio is affected by physical, cognitive, emotional and behavioral symptoms in different occupational groups in serious dimension, it can negatively affect life from business life to family life, and when it is considered to be repeated each month, the quality of life is negatively affected. In this reason the premenstrual symptoms The minimization of complaints and minimizing complaints constitutes a state of need. In the studies involved in the literature, women complaining about Premenstrual Syndrome complaints were applied to various essential oils (Rose, Sardinia, Sage, Lavender) aromatherapy and stated that depression, anxiety, anxiety, irritability pain perception decreased by both psychological and physical positive effects. In Turkey, the trend of traditional and complementary medicine is increasing day by day. However, aromatherapy practices are common in Turkey as well as aromatherapy practices in the world. The aromatic oils are diluted and ready to use are a method in pharmacies, as well as in pharmacies, as well as people want to use and use. The cost of ready‐to‐use aromatic oils will provide the treatment option to women in the light of new evidence in line with the fact that it is cheap and easily accessible to the study .

Nct (2022). "Preoperative Gabapentin vs Placebo for Vaginal Prolapse Surgery." ClinicalTrails.gov.
	Enhanced Recovery after Surgery (ERAS) is an approach to perioperative care that focuses on evidence‐based care protocols that emphasize minimizing stress and improving the body's response to stress. These protocols have resulted in a significant decrease in length of stay, complications, and cost in many different surgical specialities. Many of these protocols (including our current gynecology ERAS protocol) include preoperative gabapentin as an intervention to help reduce postoperative pain and postoperative opioid use. Gabapentin is an anticonvulsant medication that is commonly used for chronic neuropathic pain and other chronic pain disorders. The data regarding perioperative use of gabapentin is currently mixed, and the data in gynecology (and especially urogynecology) is limited. Notably gabapentin has been shown to be associated with sedation, respiratory depression, dizziness, and visual disturbances. In 2019, the U.S. Food and Drug Administration issued a warning that serious breathing difficulties may occur in patients using gabapentin with respiratory risk factors. Pelvic organ prolapse is a common benign condition, and surgery for pelvic organ prolapse is very common. Vaginal apical suspension is one of the most common surgeries for pelvic organ prolapse. There is very limited data on the utility of preoperative gabapentin for vaginal apical suspension surgery. This study will recruit women scheduled to undergo vaginal apical suspension surgery (either uterosacral ligament suspension or sacrospinous ligament fixation) with or without other prolapse or anti‐incontinence procedures. Participants will be randomized 1:1 to preoperative gabapentin or preoperative placebo (both patients and investigators will be blinded). Note the control group will receive preoperative acetaminophen/celecoxib/placebo and the treatment group will receive preoperative acetaminophen/celecoxib/gabapentin (preoperative acetaminophen/celecoxib are part of our current ERAS protocol). The primary outcome will be postoperative opioid use in the first 24 hours postoperatively measured in morphine milligram equivalents.

Nct (2022). "Preventing Childbirth-Related PTSD With Expressive Writing." ClinicalTrails.gov.
	Childbirth‐related PTSD (CB‐PTSD) is a debilitating maternal mental disorder that undermines the well‐being of mothers and can interfere with bonding with their infants during an important time of infant development. A significant portion of delivering women, particularly those who have experienced complicated deliveries, are at‐risk for developing CB‐PTSD. Underrepresented minorities are also at higher risk for CB‐PTSD. An estimated 240,000 American women are likely to be affected by CB‐PTSD each year. Currently, there is no recommended intervention for individuals exposed to traumatic childbirth in hospitals in the United States. Immediate postpartum interventions delivered to at‐risk women that are low‐cost, low‐burden, and feasible are lacking. This study will attempt to fill this gap in effective treatment. Evidence shows that expressive writing (EW), or briefly disclosing in writing mainly thoughts and feelings about a highly stressful event, can have positive effects on mental and physical health. Therefore, the investigators will test the therapeutic effects of EW about recent childbirth in women at‐risk for CB‐PTSD.

Nct (2022). "Prevention of Incontinence-associated Dermatitis." ClinicalTrails.gov.
	Incontinence‐associated dermatitis (IAD) is an inflammation of the skin caused by prolonged and direct contact of the skin with urine and/or stool. It may occur in all age groups but elderly and care‐dependent incontinent people are often affected by this type of inflammation. Promotion of continence, use of absorbent products and structured skin care are recommended to prevent and/or treat IAD. Available skin protection products can be categorized into film‐forming or lipophilic skin protectants depending on the ingredients and overall composition. Currently, there is no evidence about the superiority of one product compared to another regarding skin protection. The overall aim of this study is to compare the effects of two skin protection products compared to an untreated control group. An exploratory randomized controlled trial in incontinent elderly nursing home residents and geriatric patients will be conducted. In the two intervention groups, a film‐forming or a lipophilic skin protection product will be applied in addition to standardized skin care regimens. Every other day, investigators will perform skin inspections, including instrumental skin measurements to quantify erythema for a total study period of n= 14 days. IAD‐ related pain and itch will be assessed. A total of n= 210 nursing home residents and geriatric patients in Berlin, Germany, aged over 65 years, who are affected by urinary and faecal incontinence without signs of severe IAD will be included.

Nct (2022). "Procedural Discomfort Related to Number of Intradetrusor Botox Injections." ClinicalTrails.gov.
	This will be a single‐blinded, parallel randomized control trial (RCT) utilizing two study arms. This trial will be designed and reported as outlined in the CONSORT guidelines The primary aim of this study is to evaluate perceived discomfort using the Numeric Pain Scale (NPS) during office injection of intradetrusor BTX‐A via two different injection techniques and reconstitution volumes. The secondary aims of this study are to evaluate treatment effectiveness and patient satisfaction of treatment with BTX‐A using validated questionnaires. Investigators will also compare procedure time and post‐procedure complication rates between the two study groups. Study Groups: The patients will be randomized in a 1:1 fashion to one of two groups: ‐ 100 units BTX‐A reconstituted in 5 mL normal saline, injected into the bladder in 5 separate injections of 1 mL. One injection will be at the trigone ‐ 100 units BTX‐A reconstituted in 10 mL normal saline, injected into the bladder in 10 separate injections of 1 mL. One injection will be at the trigone The primary outcome will be measured on the day of the procedure using the NPS scale. Investigators will follow up with patients at 30 days post‐procedure to assess treatment effectiveness, overall satisfaction, and post‐procedure outcomes using validated questionnaires.

Nct (2022). "Public Health Nurse-Delivered 1-Day CBT Workshops Pilot." ClinicalTrails.gov.
	Postpartum depression (PPD) is one of the most common complications of childbirth, affecting 1 in 5 mothers. Left untreated, it increases the risk of future depressive episodes and can have profound effects on offspring. A single case of PPD has been estimated to cost as much as $150,000 over the lifespan, or $3 billion for each annual cohort of Canadian births. Current clinical practice guidelines (including those written by the NPA) recommend evidence‐based psychotherapies (e.g., cognitive behavioural therapy (CBT)) as 1st‐line treatments for the vast majority of mothers with PPD. The key role that psychotherapy plays in the treatment of PPD is further emphasized by the US Preventive Services Task Force which recommends universal PPD screening, but "only when CBT or other evidence‐based counseling is available." While treating PPD can reduce its adverse effects, safe, timely, accessible interventions are essential to optimizing outcomes. However, only treatments that can be upscaled can have an impact on PPD at the population level. The delivery of psychotherapy in large groups (up to 30 participants) is a relatively new phenomenon, but may be capable of addressing mothers' needs, as well as treating PPD on the scale required to address its prevalence. Brief (i.e., 1‐Day) interventions contain the core content of more comprehensive, evidence‐based interventions, but their brevity makes them easier to disseminate beyond traditional treatment settings (e.g., in public health). 1‐Day CBT‐Based Workshops have been delivered by trained mental health professionals (psychologists, psychiatrists) to treat generalized anxiety disorder and depression in general population samples, and postpartum depression. The purpose of this pilot study is to determine the feasibility of our study procedures and estimate the treatment effect and variance of the primary outcome in preparation for a larger RCT to determine the effectiveness of a Public Health Nurse‐Delivered 1‐Day Cognitive Behavioural Therapy‐Based Workshop for postpartum depression. A parallel‐group Ontario‐wide RCT with experimental (workshop) and TAU (control) groups will address our objectives. Participants in both groups will complete all study questionnaires and be compared at baseline, and 3 and 6 months. The experimental group will receive the Online 1‐Day workshop (delivered by 2 PHNs) in addition to TAU, and the control group will receive TAU alone. Participants will be mothers who have an infant under 12 months, who are 18 years or older, who are experiencing elevated symptoms of postpartum depression and who are free of current bipolar, psychotic and/or substance use disorders.

Nct (2022). "QL1706 Plus Chemotherapy±Bevacizumab for the First-Line Treatment of Persistent, Recurrent or Metastatic Cervical Cancer." ClinicalTrails.gov.
	Subjects must provide sufficient archival or newly obtained tumor tissue samples to determine PD‐L1 expression level to be eligible for screening.During the screening phase, eligible subjects will be stratified by use of bevacizumab (yes vs no), prior concurrent chemoradiation therapy (yes vs no), and PD‐ L1 level (CPS < 1 vs 1 ≤ CPS < 10 vs CPS ≥ 10) and randomized 1:1 into the experimental or control arm.Experimental: QL1706 + Chemotherapy (Paclitaxel‐cisplatin/Carboplatin) ± Bevacizumab;Control group: placebo + chemotherapy (paclitaxel‐cisplatin/carboplatin) ± bevacizumab

Nct (2022). "Randomized Study Of Novel Enuresis Alarm vs Standard Bedwetting Alarm." ClinicalTrails.gov.
	3.1 Problem Statement At the present time, there are no side‐by‐side comparison studies of GoGoband® vs SNEA. Since many of the prior studies were conducted using variable outcome parameters that makes direct comparisons of studies difficult it would be beneficial to obtain comparable data from the 2 groups and compare dry night rates for the 2 devices. 3.2 Purpose of Study/Potential Impact Our preliminary quality improvement data indicates that the GoGoband® is more efficacious than both medication and SNEA in an uncontrolled environment when deidentified data was analyzed off our servers. Our present database does not allow us to discern if patients are monosymptomatic nocturnal enuresis (MNE) or non monosymptomatic nocturnal enuresis (NMNE). Without this ability as well as for controlling for behavioral and academic problems which are known to affect outcomes in nocturnal enuresis studies, the investigators are not able to compare our results definitively and accurately to other treatment modalities. Hypothesis Our hypothesis is that the GoGoband® is more effective than SNEA and Desmopressin in the treatment of Nocturnal Enuresis Primary Objective The primary objective of this study is to determine whether the GoGoband®] is as effective or more effective in comparison to children who use SNEA in a population of MNE patients with no underlying Attention deficit hyperactivity disorder (ADHD) in a 3 month period. Secondary Objectives To ascertain if familial incidence of nocturnal enuresis has an effect on outcomes 5.1 General Design Description The investigators propose the following study in patients who have been evaluated for primary nocturnal enuresis in our Yale New Haven Clinics. ‐ All patients to be evaluated for nocturnal enuresis will undergo standard evaluation and initial treatment for nocturnal enuresis which includes: ‐ Assessment Of Bowel Habits, ‐ Fill Out A Questionnaire To Evaluate For Voiding Dysfunction ‐ Treatment with routine bedwetting protocol of: 1. Stopping drinks 1 HR before bedtime, meals at least 3 hrs before bedtime, eliminating milk and ice cream from dinner and on, making sure that bowel movements are occurring 4 times per week and treating appropriately if necessary. 2. On return visit bedwetters and parents will be given the option of using medication , no further treatment, or alarm therapy. 3. If patients choose alarm therapy, they will be asked if they wish to participate in the Randomized study comparing GoGoband® vs SNEA. 4. Alarms will be provided to the patients free of cost to participants 5. Patients in the alarm group will be treated for 3 months continuously. 6. Patients in the SNEA group will record nightly if they wet their clothes and the report will be recorded and reviewed weekly 7. GoGoband® patients' data will be automatically saved on the HIPPA Compliant servers and subsequently reviewed at the end of the week.

Nct (2022). "Randomized Trial Comparing Early "Trigger" Versus Delayed "Trigger" Timing in Cycles of Controlled Ovarian Stimulation." ClinicalTrails.gov.
	This randomized trial will compare the efficacy of two different times of administration of medications for final oocyte maturation, commonly called a "trigger", in cycles of controlled ovarian stimulation (COS) for cycles in which all embryos will be cryopreserved ("freeze‐all cycles"). 1. The early trigger timing will be based on sonographic observation of at least three follicles reaching at least 17mm in diameter. 2. The delayed trigger timing will be based on at least three follicles reaching at least 22mm in diameter.

Nct (2022). "A RCT on the Preventive Effect of HFNC on Postoperative Pulmonary Complications in Patients With Gynecologic Neoplasms." ClinicalTrails.gov.
	This randomized con aims to enroll patients at high risk of developing post‐operative pulmonary complications after gynecological surgery, the eligible patients will be randomly assigned to receive oxygen therapy via high‐flow nasal cannula or conventional nasal cannula. The study primary outcome is the incidence of post‐operative pulmonary complications, including postoperative hypoxemia, atelectasis, pneumonia, etc. Secondary outcomes are the improvement of postoperative oxygenation, antibiotic use, length of hospital stay, adverse events related to oxygen therapy, etc.

Nct (2022). "Recombinant Follicle-stimulating Hormone in Treatment for Infertility." ClinicalTrails.gov.
	This is a randomized multi‐centre, assessor‐blind, parallel‐group study to be conducted in 250 women in the age group of 20 to 39 years (both inclusive), who are indicated to undergo COS as part of assisted reproductive technology (ART). The participant will receive r‐hFSH, fixed‐dose for 5 days, and day 6 onwards the dose may be adjusted for a single cycle of COS followed by ART procedures, and post‐ART follow‐up for ongoing pregnancy. The primary and secondary outcomes will be captured on days as per protocol. Adverse events will be noted for safety evaluation.

Nct (2022). "Reduced-dose Botox for Urgency Incontinence Among Elder Females." ClinicalTrails.gov.
	The purpose of this quadruple‐masked, randomized‐controlled study is to study the treatment of urgency urinary incontinence (UUI) specifically among older women with low‐ versus standard‐dose of onabotulinumtoxinA (BTX) via: symptom‐specific and health‐related quality of life (QOL; Aim 1), patient‐reported and clinical outcome measures including adverse events (Aim 2), qualitative experience with focused interviews (Aim 3) and cost burden and economic impact (Aim 4). This study is an active collaboration between researchers in Gynecology, Urology, and Geriatrics at Dartmouth Hitchcock Medical Center (DHMC) and at 5 other centers; University of Alabama (UAB), University of Pittsburgh (U Pitt), University of Texas Southwestern (UTSW), Kaiser Permanente of Southern California (KPSCP), and Oregon Health & Sciences University (OHSU). The investigators also have collaborators at Stanford University and University of Connecticut, though those sites are not recruiting participants.

Nct (2022). "Relacorilant in Combination With Nab-Paclitaxel in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer." ClinicalTrails.gov.
	As there are no currently approved therapies or effective standard of care for heavily pretreated patients with ovarian cancer who have exhausted single‐agent chemotherapy and/or bevacizumab, the combination of intermittently administered relacorilant and nab‐paclitaxel may demonstrate a substantial improvement without increased toxicity compared with nab‐paclitaxel. Patients will receive study treatment until confirmed progressive disease (PD) or unacceptable toxicity. All patients will be followed for the collection of study endpoints, inclusive of disease progression and survival.

Nct (2022). "Relaxation Exercises for Low Back Pain and Insomnia in the Third Trimester of Pregnancy." ClinicalTrails.gov.
	In 2021 the research says that most women experience pubic pain, hip pain, knee pain, leg cramps, carpal tunnel syndrome, De Quervain's tenosynovitis, or at least one of these symptoms during pregnancy and approximately one‐quarter of them have a temporary disability. Symptoms of LBP could start from early in pregnancy until giving birth, but usually, the pain becomes more severe during the third semester of pregnancy and is described as a dull pain. In most cases of LBP, the pain does not radiate to other parts of the body. The exercise was found to be a very common practice used to decrease LBP and the majority of the relative studies were categorized as of high methodological quality. The exercise components of the interventions included strength and stretching, endurance training, pelvic tilt exercises, stretching and mild isometric abdominal contractions, progressive muscle relaxation exercises accompanied by music as well as aerobic and stretching exercises. Another research in 2021 describe that one of the most common complaints during pregnancy is sleep disorders, such as insomnia, frequently waking up at night, high drowsiness during the day, mood swings, and unusual feelings during sleep results of the present study showed that counseling with a spiritual approach was effective in improving the sleep quality in pregnant women. In the intervention group, the mean score of sleep quality decreased in the second and third trimesters compared to the control group. In the present study, spiritual content counseling had a significant effect on all areas of sleep quality, except for habitual sleep efficiency. In 2018 one of research says that physiological and psychological changes in the third trimester of pregnancy make falling asleep at night more difficult for pregnant women. Studies also show that relaxation exercises reduce psychological tension, stress, and pain. The pregnant women in the relaxation exercises group of the present study reported falling asleep more comfortably as a result of the decrease in muscle tension, stress, and pain perception. The four‐week relaxation exercises improved subjective sleep latency, duration, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and sleep quality of the pregnant women in the third trimester. Another research in 2018 on the effects of breathing exercises on insomnia. This study finding revealed that, pre‐intervention more than half of the pregnant women experienced severe insomnia this may be attributed to the inflammation process of pregnancy and the effect of pregnancy physiological and psychological changes and discomforts on the sleep cycle. The present study revealed that the total score of insomnia decreased for the majority of pregnant women after practicing walking with deep breathing exercises. This can be attributed to the positive effect of exercises i.e walking or breathing exercises on the overall health either physical or psychological by improving physical fitness, increasing the blood supply and the circulation to the brain to enhance the sleep cycle, and improving the quality of sleep and decrease the insomnia symptoms. It has a positive effect on the severity of insomnia during the third trimester of pregnancy, tension, and fatigue relief. Another research in 2014 says that relaxation therapy and progressive muscle relaxation (PMR) are forms of complementary and alternative medicine often used in pregnancy. There are several reasons why this therapy might produce the observed benefit. PMR‐induced reduction in anxiety and decreased perception of pain may eventually improve QOL status in pregnant women. In one study, PMR intervention was compared with massage in pregnant women with leg and back pain. In that study, leg pain decreased significantly after the first and last treatments in both the PMR and massage groups, but back pain decreased only in the massage group. Pain decreased over time during the study in the intervention group, whereas the pain scores (and perceived pain) in the control group increased gradu ly. LBP is one of the most common symptoms in pregnancy. We conclude that PMR training can reduce LBP and improve QOL in pregnant women. Most of the research was conducted on low back pain with pelvic girdle pain, the effect of relaxation exercises with music on low back pain, the effect of relaxation exercises on insomnia, and quality of life. The objective of this research is to determine the effect of progressive relaxation exercises on low back pain and insomnia in the third trimester of pregnancy and show the combined effect of relaxation. Reviewing the previous literature on the effects of exercises on low back pain and insomnia provides sufficient data but there is not enough data on the effects of a combination of both exercise on insomnia and low back pain.

Nct (2022). "The Role of Clean Intermittent Catheterization in Patients Undergoing Radiotherapy After Radical Hysterectomy for Cervical Cancer." ClinicalTrails.gov.
	In this study, patients with postoperative radiotherapy for cervical cancer complicated with voiding dysfunction in the Department of gynecology and oncology radiotherapy of our hospital from July 2018 to December 2020 were selected as the research objects. At the beginning of the study, a total of 80 people were randomly divided into two groups: 40 cases in the observation group and 40 cases in the control group. The observation group implemented intermittent catheterization and formulated a reasonable bladder rehabilitation training plan, and the control group received routine indwelling catheterization. The observation group gave one‐to‐one training and education to patients and their families before the implementation of the project, including 1. Watching the operation video of intermittent catheterization for female patients. 2. The nurse demonstrated on the simulator. 3. Distribution of drinking water and urination plan, such as paper urination plan, etc. Drinking water plan: patients are required to drink about 1800ml‐2000ml of water every day, including drinking water, soup, fruit, etc. it is recommended that the water intake for three meals in the morning, noon and evening is 400ml respectively, and about 200ml water is taken between meals. 200ml water is taken 2 hours after dinner, and no water is taken 2‐3 hours before going to bed. Frequency and timing of intermittent catheterization: it is recommended to catheterize once every 4 hours and no more than 6 times every 24 hours. If the residual urine volume decreases, the number of catheterization can be appropriately reduced; Before each catheterization, urinate by yourself. The derived urine volume is the residual urine volume. The total amount of urine shall not exceed the safe capacity of the bladder. 4. The nurse guides the catheterization with hands on the patient until the patient or family members fully master the operation. 5. Nurses add wechat to patients or their families to answer patients' questions and solve operational problems at any time; For three consecutive days after the beginning of intermittent catheterization, patients need to take photos and upload their drinking water and urination diaries every day. Nurses assess the existing risks and deficiencies, give guidance and continue to follow up. 6. If the residual urine volume of the patient is less than 100ml or less than 20% of the safe capacity of the bladder for 3 consecutive days, it is judged that the bladder function has been restored and intermittent catheterization can be stopped. 7. In case of adverse events during the implementation of the project, such as urinary tract infection and impaired renal function, it is necessary to communicate with the doctor in time to decide whether to continue intermittent catheterization. During radiotherapy, the bladder function of the observation group and the control group was evaluated every 7 days until the end of radiotherapy. All patients need to fill in SF‐36 questionnaire before and after radiotherapy. In principle, the questionnaire star or paper questionnaire is required to be filled in by the patients themselves. For those who can communicate but can not read and fill in by themselves, the family members shall assist in completing it together. All options of the scale are required to be the opinions of the patients themselves. Drinking water and urination diary records shall be completed by patients and their families. The general information of patients is completed by medical staff at the end of radiotherapy.

Nct (2022). "Role of Oral Lactoferrin in Prevention of Recurnt Bacterial Vaginosis in Pregnancy." ClinicalTrails.gov.
	This study will be conducted at Zagazig University Hospitals, Obestetrics and Gynecology department, Zagazig University ,outpatient clinic .Assuming the cure rate was 70.8% vs 33.3% in intervention vs placebo group. At 80% power and 95 % CI, the estimated sample will be 66 cases, 33 cases in each group. Among enrolled women those who have symptome of bacterial vaginosis will be treated with standard antibiotic therapy (metronidazole 500 mg twice daily for 7 days) and women who have history of recurrent bacterial vaginosis randomly assigned to one of two study arms: study grop receiving lactoferrin (2 capsules/day for 5 days followed by further 10 consecutive days at the dosage of 1 capsule/day) by oral intake.(pravotinR). And another group not reciving lactoferrin.(control group) During follow‐up period, all women ingested 1 capsule of lactoferrin or placebo per day, for 10 consecutive days per month.(study group) . ‐ All participating women attended 3 visits (from T0 to T2) at the gynaecologic centres at recruitment (T0), swap will be repeated after one month (T1) and two months (T2). In each clinical examination, 2 vaginal swabs (for vaginal culture and Nugent score) will be collected. During the first visit (baseline), patient medical history was recorded, informed consent was signed and women were allocated into the two study arms. ‐ The evaluation of efficacy is based on clinical cure rate of BV symptoms (defined as absence of vaginal discharge or itching), microbiological cure rate (defined as remission and vaginal microbiota improvement by restoration of healthy Nugent score with range 0‐3), and overall cure rate (absence of symptoms and Nugent score <7). In addition, recurrence rate was calculated for both groups as percentage of women presenting with symptoms and Nugent score more than 3 during the follow‐up period. Safety is assessed by recording all side effects (i.e. adverse events, serious adverse events, and suspected unexpected serious adverse reactions). An adverse event is considered severe if it was fatal, life threatening, required hospitalisation, or led to permanent injury.

Nct (2022). "The Role of Sugammadex in Posotoperative Urinary Retention in Patients Undergoing Pelvic Floor Reconstructive Procedures." ClinicalTrails.gov.
	The Investigator will perform a single‐institution randomized double‐blinded controlled trial comparing intraoperative Sugammadex vs. standard dose of glycopyrrolate/neostigmine combination for participants undergoing a total vaginal hysterectomy with or without pelvic organ prolapse procedures under general endotracheal anesthesia.

Nct (2022). "Secondary Cytoreduction Followed by Chemotherapy Versus Chemotherapy Alone in Relapsed Ovarian Cancer After PARPi Maintenance Treatment: a Multicentre, Open-label, Randomised, Phase 3 Trial." ClinicalTrails.gov.
	This study aims to carry out a multi‐center, randomized controlled study on patients with recurrent ovarian cancer after PARPi maintenance, to explore the clinicopathological and molecular characteristics of patients with recurrent ovarian cancer after PARPi maintenance, and to clarify whether patients with recurrent ovarian cancer after PARPi maintenance for more than 6 months are sensitive to platinum drugs, and the value of secondary tumor cell reduction in such treatment, In order to provide evidence‐based medicine basis for the standardized treatment mode of recurrent ovarian cancer after PARPi maintenance treatment.

Nct (2022). "Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	To investigate the efficacy of semaglutide in obese infertile women of childbearing age with polycystic ovary syndrome (PCOS), we design this prospective, randomized, open and controlled study. 75 obese infertile PCOS patients will be recruited and randomized into three groups: metformin, semaglutide and metformin+semaglutide, on the basis of calorie‐restricted diet and physical exercise. Metformin and semaglutide will be administered in a dose increasing mode, and then maintain until the end of 12 weeks, and metabolic related indexes will be evaluated. After 12 weeks of treatment, all subjects will stop taking the drug for at least 8 weeks to initiate ovulation induction or ovulation induction combined with artificial insemination. All subjects will be followed up for 24 weeks to evaluate the fertility related indicators. The primary endpoint of the study is the percentage of weight loss at 12 weeks of treatment. The secondary endpoints include HOMA‐IR and androgen levels at 12 weeks of treatment, ovulation rate at 24 weeks of follow‐up, clinical pregnancy rate and cumulative pregnancy rate, and depression, anxiety, diet and quality of life scores at 12 weeks of treatment.

Nct (2022). "Serial Screening and Treatment of Bacterial Vaginosis Trial." ClinicalTrails.gov.
	Preterm delivery affects 10% of all pregnancies in the United States. This risk is further increased in pregnant women with a history of preterm delivery. There are multiple etiology contributing of preterm labor. Of these, the presence of inflammation and infection have been a well‐established cause. Bacterial vaginosis (BV), a common vaginal infection in pregnancy, may often be asymptomatic. Studies demonstrate a strong association between BV and preterm labor. Therefore it is recommended that women at high risk for preterm delivery are treated for this infection irregardless of symptoms. In this study the investigators hypothesize that increased testing for bacterial vaginosis, with subsequent timely treatment, may decrease the risk of preterm delivery in patients who are at high risk. The investigators suspect that the increase in monitoring will help diagnose asymptomatic bacterial vaginosis infections allowing for prompt treatment and avoidance of preterm labor. Subjects will be randomized in a two‐arm study to undergo predetermined intervals of testing for bacterial vaginosis or control. No experimental drugs or devices will be used. ‐ The intervention‐arm will have a pelvic exam performed with vaginal swab collection at their initial obstetric visit. The women undergoing the intervention will then subsequently undergo additional vaginal swab collections in 2 week intervals starting at 16 weeks gestational age until 34 weeks gestational age. ‐ The control arm will undergo the standard of care. There will be no placebo for the control group.

Nct (2022). "SMS Messaging for Invitation in the Cervical Cancer Screening Programme." ClinicalTrails.gov.
	Main Hypothesis: The use of direct SMS without an explanatory call for cervical cancer screening invitation is an acceptable option to invite women if the participation obtained is more than 70% and not less than 15% of the call (current practice). Specific Hypothesis: ‐ Participation in cervical cancer screening programme using SMS invitation is non‐inferior to 70%. ‐ Participation in cervical cancer screening programme using telephone call is non‐inferior to 70%. ‐ Participation using SMS invitation is non‐inferior to participation using telephone call invitation, considering that an absolute difference less than 15% may not be clinically relevant. Sample size calculation: A one‐sample non‐inferiority test for calculating sample size was performed, assuming a participation rate of 80% using SMS invitation and 85% using telephone call invitation in the cervical cancer screening programme. To detect a participation rate using SMS or telephone call invitation non‐inferior to 70%, with a margin of 5%, accepting an alpha risk of 0.025 and a beta risk of 0.2, and 5% of loses of follow‐up, we will need 27 women in the telephone call group and 59 women in the SMS group. To observe this non‐inferiority by age group (≤40 years, 41‐54 years, ≥55 years), 27 and 59 women will be needed for each age group. To compare both study arms, a two‐sample non‐inferiority test was performed assuming that using SMS messages to invite women to participate in cervical cancer screening programme will be 5% lower compared to participation when invitation is performed by a phone call (80% versus 85% respectively), although this difference will be non‐inferior to 15‐15.5%. Thus, if there is a true difference in favor of the telephone call group of 5%, assuming 5% of loses of follow‐up, then 450 women will be required (225 in each arm) to be 80% sure that the upper limit of a one‐sided 97.5% confidence interval will exclude a difference in favor of the SMS group of more than 15‐15.5%. Randomization procedure: Women will be randomized in two study arms: intervention (SMS message invitation) and control (telephone call invitation). Randomization will be performed based on permuted blocks of 6 women to ensure equal distribution among age groups.

Nct (2022). "The SPROUT (Pilot) Project." ClinicalTrails.gov.
	Historically, pregnant women were advised to refrain from exercise due to concerns of maternal and fetal risk such as preterm delivery, low infant birth rate and fetal stress. Despite current research that has demonstrated substantial benefits for maternal, fetal, and infant health, only 9‐15% of pregnant women meet the current physical activity recommendations. In addition, pregnancy exercise research is confounded by a lack of randomized controlled trials (RCT) that include diversity in participant demographics, specifically inner city populations, and difficulty accurately quantifying weekly exercise volume. The investigators propose a pilot RCT investigating two different approaches to exercise intervention across a spectrum of demographics that the investigators believe will result in improved exercise adherence as well as in maternal and infant health outcomes. Specific Aim #1: To determine the feasibility of two types of exercise interventions (supervised & home exercise) in terms of design, implementation and adherence. Our working hypothesis is that both supervised and home exercise interventions will be implementable as designed in pregnant women as evidenced by recruitment, eligibility, retention, follow‐up and exercise adherence from 1st trimester through 6‐months post‐natal at a 60% rate, but that adherence to the two types of exercise interventions will differ by demographic. A secondary exploratory hypothesis is that the investigators will be able to successfully recruit and retain 50% of our pregnant women from the Syracuse Community Health Center (primarily women with lower resources). Specific Aim #2: To determine the appropriateness of the outcome measures proposed for the exercise intervention in detecting changes in maternal aerobic fitness, quality of life (QOL), fatigue, sleep quality, depression, and weight change throughout pregnancy and 6‐months post‐natal as measured by the Balke Ware submaximal test; SF‐12 Generic Quality of Life (QOL); Multidimensional Fatigue Inventory (MFI); Pittsburgh Sleep Quality Index (PSQLI); Center for Epidemiologic Studies Depression Scale (CES‐D); Edinburgh Postnatal Depression Scale (EPDS); and the Pregnancy Physical Activity Questionnaire (PPAQ). Our working hypothesis is that the above outcome measures will be able to detect changes in maternal outcome measures in both exercise groups. Because this is a feasibility study, the results will be used as preliminary data to apply for future funding and also will provide variable quantitative and qualitative data for validating interventions that can increase adherence to exercise guidelines during pregnancy in women with different ethnic and socioeconomic backgrounds.

Nct (2022). "Stress Urinary Incontinence Study to Assess Safety and Efficacy of Muvon's Muscle Precursor Cell Therapy." ClinicalTrails.gov.
	Stress urinary incontinence is the loss of small amounts of urine associated with coughing, laughing, sneezing, exercising or other movements that increase pressure on the abdomen and therefore increasing the pressure on the bladder. The goal of the SUISSE MPC2 study is to treat SUI in women using their own autologous muscle precursor cells. To guarantee enough outcome data, a sufficient number of patients will be enrolled to complete the study with 70 patients. The study will last approximately 8‐9 months per patient. Each patient's baseline measurements serve as comparison for the treated measurements. Patients will participate in the study for up to approximately 8 to 9 months, including a baseline visit for screening, a visit to obtain a muscle biopsy up to 12 weeks later, an injection of MPCs up to 5 weeks later, and follow‐up visits after 1, 3 and 6 months post injection. The injection is performed with ultrasound guidance using an endocavity ultrasound probe mounted on an Injection Device specifically designed for the clinical trial. All patients will be treated with one of the two doses of MPCs, assigned according to the study's randomization method. Half of the participating patients will receive the cell therapy that was previously studied in the completed phase I study. The other half of the participants will receive a higher dose of the cell therapy to investigate the effects of dose increase. Both groups of patients will be additionally monitored by medical examinations performed by clinicians to ensure the safety of the treatment. Furthermore, separate to the Principal Investigator, safety events will be reported to and investigated by the independent Data Safety Monitoring Board consisting of independent physicians and experts in the field. Data regarding the functionality and safety of the Injection Device will also be collected.

Nct (2022). "A Study Comparing Perioperative Stress Reduction vs. Standard of Care in Ovarian Cancer (PRESERVE)." ClinicalTrails.gov.
	The purpose of this study is to see if propranolol and etodolac along with mind‐body resilience training/MBRT and music therapy help participants who are experiencing physiological stress before, during, and after primary debulking surgery/PDS or IDS and also if it's better than the standard‐of‐care approach (no intervention for reducing stress).

Nct (2022). "Study Evaluating the Efficacy and Safety of a Digital Therapeutic as an Adjunct to TAU in Postpartum Depression." ClinicalTrails.gov.
	This randomized, double‐blind, controlled trial evaluates the efficacy and safety of 8 weeks of treatment of two digital therapeutics in a population of women with mild to moderate postpartum depression. Patients will be referred by an obstetrician, pediatrician, or other healthcare professional, or by other digital and site based recruitment methods and, if interested, will complete the pre‐screening process. Those confirmed as eligible will be scheduled to attend a screening/baseline onsite visit. Eligible participants will be randomized to one of the two groups and will receive instructions on downloading and using the smartphone application to which they were randomized. Participants will use the app as instructed and will attend telehealth visits to complete assessments for the primary and safety endpoints at Weeks 4 and 8 (EOT).

Nct (2022). "A Study of AK104/Placebo Combined With Chemoradiotherapy For The Treatment of Locally Advanced Cervical Cancer." ClinicalTrails.gov.
	This study is to evaluate the efficacy and safety of AK104 plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer

Nct (2022). "Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions." ClinicalTrails.gov.
	This is an investigator‐initiated prospective, national multicentre, phase III, randomised, open, non‐inferiority clinical study. The study hypothesis is that adjuvant radiotherapy decision for early‐stage endometrial cancer which is based on molecular classification can achieve de‐escalation of adjuvant treatment without reducing local tumour control and survival, thereby potentially further reducing radiotherapy‐related toxicity and improving quality of life, compared to using conventional risk stratification. The primary endpoint of this study is the 3‐year local recurrence rate.

Nct (2022). "A Study of GLS-010 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer." ClinicalTrails.gov.
	This is a randomized, double‐blind, placebo‐controlled phase III study，aimed to evaluate the efficacy and safety of GLS‐010 plus platinum‐containing chemotherapy with or without bevacizumab as first‐line treatment for persistent, recurrent, or metastatic cervical cancer.All enrolled patients will be randomly divided into 2 groups and continuously treated until any event that meets the criteria for end of the clinical trial.

Nct (2022). "A Study of Incoxil Food Supplement in Female Patients With Stress Dominant Urinary Incontinence." ClinicalTrails.gov.
	Pelvic floor muscle training (PFMT) is the first line therapy recommended for the treatment of stress urinary incontinence. The study aims to investigate how poor pelvic floor muscle function can be strengthened by performing pelvic floor exercise and using a special dietary supplement at the same time, and if stress urinary incontinence can be improved more effectively than by performing pelvic floor exercise alone. The study aims to compare the clinical improvement in the symptoms of stress urinary incontinence in women who do pelvic floor muscle training exercise (PFMT) or who do PFMT exercise and use a dietary supplement. Incoxil dietary supplement contains ingredients that are specifically designed to help strengthen muscles (creatine, l‐leucine, zinc, calcium and magnesium). The randomized controlled clinical trial is proposed involving 34 women diagnosed with stress dominant urinary incontinence and randomized into two groups: 1) treatment with Incoxil dietary supplement and PFMT; 2) treatment with placebo dietary supplement and PFMT. All women will perform PFMT daily and women in group 1 take Incoxil every day, while women in the control group will take daily placebo dietary supplement for 6 weeks. At baseline assessment, patients shall undergo anamnesis, general gynecological exam, assessments of the pelvic floor based on the modified Oxford scale, the presence of prolapse using the Pelvic Organ Prolapse Quantification (POP‐Q) system, pelvic muscle contraction will be measured using a pelvic Perineometer and Vaginal Tactile Imaging will be used for evaluation of vaginal and pelvic floor conditions. We also assess the general health of the vagina with Vaginal Health Index scores. Participants shall complete UDI‐6, PGI‐S/I and IIQ‐7 questionnaires. After 6 weeks treatment the same assessments will be done to compare treatment and control group results.

Nct (2022). "A Study of the Use of Vaginal Radiofrequency Therapy in Treatment of SUI." ClinicalTrails.gov.
	Before treatment, patients with mild and moderate stress urinary incontinence were diagnosed according to the diagnostic criteria through medical history inquiry and gynecological physical examination, and patients were screened according to the inclusion and exclusion criteria. After informing two treatment plans and signing the informed consent, they were randomly divided into vaginal radiofrequency therapy group and electrical stimulation combined biofeedback group. After being included in the test, one hour urine pad test was conducted, and IIQ‐7, PISQ‐12 and FSFI questionnaires were completed. IIQ‐7, PISQ‐12 and FSFI questionnaires were followed up 1, 3, 6 and 12 months after treatment. After 3 months and 1 year of treatment, 1 hour urine pad test was given again.

Nct (2022). "A Study to Evaluate Safety and Efficacy of Elagolix in Patients With Moderate to Severe Endometriosis-Associated Pain." ClinicalTrails.gov.
	This is a Phase 3, multicenter, double‐blind, placebo‐controlled, randomized study to assess the safety and efficacy of elagolix versus placebo in premenopausal 18 to 49 year old women with moderate to severe endometriosis‐associated pain. Participants will be randomised in a 1:1 ratio to receive either elagolix ( 200mg )or placebo. Participants will be administered the study drug up to month 6.

Nct (2022). "A Study to Learn How Safe the Study Treatment Elinzanetant is and How it Moves Into, Through and Out of the Body When Given as Single Increasing Doses That Are Higher Than Normally Used Compared to Placebo and Moxifloxacin in Healthy Participants." ClinicalTrails.gov.
	Researchers are looking for a better way to treat vasomotor symptoms, a condition of having hot flashes. The condition is caused by hormonal changes and occurs primarily in women, but can also affect men. The study treatment, elinzanetant, is under development to treat symptoms caused by hormonal changes. It works by blocking a substance called neurokinin from sending signals to other parts of the body, which is thought to play a role in starting hot flashes. Participants of this study will be healthy and will have no benefit from administration of elinzanetant. This study, however, will provide information on how to use it in people with vasomotor symptoms. In previous studies, elinzanetant doses tested and resulting blood levels were close to the levels intended for treatment. However, in future use, it cannot always be ruled out that higher elinzanetant concentrations may occur in the blood if patients are taking certain other drugs at the same time, or take more than the recommended dose of the drug. The main purpose of this study is to learn how safe elinzanetant is when higher doses than normally used are given compared to placebo in healthy participants. A placebo is a treatment that looks like a medicine but does not have any medicine in it. To answer this, researchers will compare the number of participants who have medical problems after taking elinzanetant to those treated with placebo. Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study treatments. The study consists of two parts. In part 1, the participants will either take a single dose of elinzanetant or placebo by mouth dependent on the treatment group. Four different increasing doses of elinzanetant will be tested. Participants in dose group 1 and 4 will participate in part 2. About 8 days after treatment in part 1, the participants will receive a single dose of moxifloxacin and a single dose of placebo as tablet by mouth 5 days apart. Whether the participant starts with moxifloxacin or placebo is decided by chance. Moxifloxacin is used to make sure that certain changes in heart rhythm can be detected in the study. Each participant will be in the study for about 6 weeks including 1 treatment day (part 1) or for about 8 weeks including 3 treatment days (part 1 & 2). Participants of part 1 will stay in‐house for 7 days. Participants of part 2 will stay in‐house for another 9 days. The in‐house phase starts two days before intake of the study treatment. In addition, one visit before and one visit after the in‐house phase to the study site is planned. During the study, the study team will: ‐ Do physical examinations ‐ Check vital signs ‐ Take blood and urine samples ‐ Examine the participants' heart health using electrocardiogram (ECG) ‐ Ask the participants questions about their mood and about sleepiness.

Nct (2022). "Subdermal Implant-bioabsorbable Gestrinone Pellet for Endometriosis Pelvic Pain Treatment." ClinicalTrails.gov.
	This is a phase II study, multicenter, prospective, randomized, double‐blind and placebo‐controlled study to evaluate the safety and tolerability of of subdermal implant‐bioabsorbable gestrinone pellet use in women with pelvic pain secondary to endometriosis. The exploratory aim is to compare the use of a gestrinone pellet with a placebo pellet in the results of participant satisfaction, change in pelvic pain intensity, use of rescue pain medication, quality of life, sexual function, and work activity. One hundred patients will be randomized in a 1: 1 ratio. Initially, all the patients will undergo insertion of an intrauterine system of levonorgestrel release (Kyleena) as a contraceptive method. On the same day, after randomization, the subdermal implantation of the gestrinone (85 mg) or placebo pellet will be performed. Visits will occur after 3 and 6 months of the pellet insertion. Primary endpoint is a combination of serious adverse events (SAEs) accumulated within 6 months of pellet insertion and collected through spontaneous reporting and/or clinical findings.

Nct (2022). "The Supporting Understanding of PCOS Education and Research (SUPER) Study." ClinicalTrails.gov.
	This research will test whether a Dietary Approaches to Stop Hypertension (DASH) or a very low‐carbohydrate diet better improves outcomes like blood glucose control and body weight for adults with polycystic ovary syndrome. Participants will have screening (includes blood draw) and baseline testing with a continuous glucose monitor and a body composition scan (called a dual‐energy x‐ray absorptiometry or DEXA). Once these enrollment steps are completed and the participants will be randomized to one of two 12‐month programs.

Nct (2022). "Suturing Techniques on Perineal Pain." ClinicalTrails.gov.
	Recruitment will be carried out at OU Medical Center within a 12‐month period either at OU Women's Pelvic and Bladder Health Clinic or OU Women's Health Clinic. Women who are planning pelvic organ prolapse repair and who are found to have genital hiatus of ≥4 cm on the pelvic organ prolapse quantification exam will be approached for study inclusion. A 4‐cm or greater dimension of genital hiatus is associated with greater risk of prolapse recurrence, and researchers anticipate patients with this measurement prior to surgery will require a perineorrhaphy. These surgeries will be performed by one of two board certified female pelvic medicine and reconstructive surgery specialists. Given the nature of the suturing techniques, it would be impossible to blind the study to both the investigators and the participants. Randomization will be completed prior to the procedure and contained within opaque sealed envelopes until a decision is made to proceed with a perineorrhaphy intraoperatively. To standardize the procedure, an instructional video will be made to describe the subcuticular and transcutaneous interrupted techniques. This will serve as reference for investigators to adhere to the standard procedure. An educational webinar will be performed at the onset of the study and this instructional video will be available for review at any additional point during the study. Participants will be asked to complete a baseline SPS questionnaire prior to surgery. Perineorrhaphy will be carried out in our standard fashion and finalized with interrupted stitches of delayed absorbable monofilament sutures for reconstruction of the perineal body. The perineal skin closure will be randomized to continuous subcuticular or interrupted transcutaneous stitches of 3‐0 polyglactin‐910 (Vicryl). Researchers will follow the standard Enhanced Recovery After Anesthesia (ERAS) protocol for postoperative oral analgesia. Participants will be asked to complete daily SPS questionnaires in the first two weeks postoperatively. Patients are routinely scheduled for a 2‐ week and 3‐ month postoperative visit. Participants will complete a questionnaire to assess pain (SPS) and patient satisfaction at both visits. A pelvic exam is not routinely performed at the 2‐week visit unless indicated otherwise by patient or provider concerns. At the 3‐month postoperative visit, a sexual function questionnaire and a pelvic exam will be completed in addition to the pain and patient satisfaction survey. These surveys can be administered in person or remotely (by telephone or virtually), depending on the nature of the postoperative visits.

Nct (2022). "Symptom Monitoring and Menopausal Symptoms." ClinicalTrails.gov.
	A recent systematic review suggested that symptom monitoring can result in reductions in menopausal symptoms and improvements in health‐related behaviours. To date, no studies have experimentally investigated whether symptom monitoring could be beneficial as an intervention for menopausal women. One hundred menopausal women were randomised into either a Monitoring‐intervention or Control group. A mixed between/ within design was employed, with group membership (i.e., Monitoring‐intervention or Control) as the between‐subjects component, and time (i.e., baseline and 2‐weeks follow‐up) as the within‐subjects component. Dependent variables included symptom reductions and emotional reactions. Secondary outcomes included help‐seeking, communication, medical decision‐making, health awareness, self‐efficacy, and health anxiety.

Nct (2022). "Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial." ClinicalTrails.gov.
	PRIMARY OBJECTIVE: I. To register, allocate, and assign patients to ComboMATCH treatment trials. SECONDARY OBJECTIVES: I. To evaluate the rate of positive outcomes in defined cohorts within treatment trials of treatment combinations including targeted therapies for molecularly defined populations, and also in the subset of treatment trials where the treatments are supported by in vivo models. II. To perform quality control of the patients registered in the form of pathological confirmation of disease and sub‐type to confirm diagnosis and treatment arm allocation. SECONDARY CORRELATIVE OBJECTIVES: I. Assess the concordance of the central molecular characterization of the pre‐treatment biopsy samples with the genetic readouts from the Designated Laboratories (DLs) for patients enrolled on the ComboMATCH treatment trials. II. To assess how the registration diagnostic tumor mutation profile and pre‐treatment biopsy profile compare to the circulating tumor‐derived deoxyribonucleic acid (ctDNA) mutation profile from plasma. EXPLORATORY OBJECTIVE: I. Assess association between ComboMATCH treatment trials outcomes (positive or negative) with the type of rationale for the selected drug combinations and the type of rationale for the gene variant/combination for selection (e.g., whether the trial was based on targeted therapies for molecularly defined populations, those that were supported by in vivo models, and those that were supported by empiric clinical data). OUTLINE: REGISTRATION: Patients undergo tumor mutational screening of previously‐collected tumor samples for specific, pre‐defined mutations, amplifications, or translocations of interest via tumor sequencing. Patients who are 18 years or older and have biopsiable disease undergo a new biopsy for research purposes prior to initiating treatment on the ComboMATCH treatment trial. TREATMENT: Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols. EAY191‐N4: Patients with RAS pathway mutant ovarian or endometrial cancer are randomized to 1 of 2 arms. ARM I: Patients receive selumetinib PO and olaparib PO on study. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. ARM II: Patients receive selumetinib PO on study. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. EAY191‐N2: Patients with NF1 nonsense or frameshift mutations or NF1 gene deletion, and hormone receptor positive, HER2‐negative metastatic breast cancer. Patients who are fulvestrant naive are assigned to Cohort I, while patients who are fulvestrant resistant are assigned to Cohort II. COHORT I: Patients are randomized to 1 of 2 arms. ARM I: Patients receive fulvestrant intramuscularly (IM) and binimetinib PO throughout the trial. Patients also undergo a CT, magnetic resonance imaging (MRI), or bone scan and tumor biopsy during screening and on study. ARM II: Patients receive fulvestrant IM throughout the trial. Patients who progress on fulvestrant alone are asked to reaffirm their willingness to enroll in cohort II. Patients not willing to transition to cohort II continue further therapy as clinically indicated. Patients undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study. COHORT II: Patients receive fulvestrant IM and binimetinib PO throughout the trial. If the patient progressed on fulvestrant, the loading dose of fulvestrant is omitted. Patients undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study. EAY191‐E4: Pat nts with solid tumors who previously underwent taxane therapy. Patients receive nilotinib hydrochloride monohydrate PO twice daily (BID) on days 1‐28 and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow‐up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression. EAY191‐A3: Patients with KRAS/NRAS/BRAF mutated low‐grade serous ovarian cancer (LGSOC) naive to MEK or CDK4/6 inhibitor therapy are randomized to either combination cohort 1 or monotherapy cohort 1. Patients with LGSOC who have received prior MEK inhibitor therapy are assigned to combination cohort 2. Patients with KRAS/NRAS/HRAS/non‐V600E BRAF mutated pancreatic cancer are assigned to combination cohort 3. Patients with all other KRAS/NRAS/HRAS mutated tumor types (excluding LGSOC, non‐small cell lung cancer, colorectal cancer, pancreatic, and melanoma) are assigned to combination cohort 4. COMBINATION COHORTS 1, 2, 3, 4: Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up. MONOTHERAPY COHORT 1: Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up. EAY191‐S3: Patients with an activating AKT mutation solid tumor. Patients receive paclitaxel IV and ipatasertib PO on study. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and follow‐up. EAY191‐A6: Patients with RAS/RAF/MEK/ERK mutant biliary tract cancers are randomized to 1 of 2 arms. ARM 1: Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo echocardiogram (ECHO) and multigated acquisition scan (MUGA) during screening and on study, a CT with contrast, MRI, or a fludeoxyglucose F‐18 positron emission tomography (FDG‐PET) during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated. ARM 2: Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG‐PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated EAY191‐E5: Patients are assigned to 1 of 2 cohorts. COHORT I: Patients who have never received a KRAS G12C inhibitor randomized to arms A or B. ARM A: Patients receive sotorasib PO and panitumumab IV on study. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up. ARM B: Patients receive sotorasib PO on study. Patients with disease progression may cross‐over to cohort II. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up. COHORT II: Patients who have received a KRAS G12C inhibitor assigned to arm C. ARM C: Patients receive combination therapy as in Arm A. EAY191‐A2: Patients are assigned to 1 of 3 cohorts. COHORT 1: PARP‐inhibitor naive patients are a igned to Arm A. ARM A: Patients receive olaparib PO BID and alpelisib PO daily on days 1‐28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. COHORT 2: PARP‐inhibitor naive patients are randomized to 1 of 2 arms. ARM B: Patients receive olaparib PO BID and alpelisib PO daily on days 1‐28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. ARM C: Patients receive olaparib PO BID on days 1‐28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. COHORT 3: PARP‐inhibitor resistant patients are assigned to Arm D. ARM D: Patients receive olaparib PO BID and alpelisib PO daily on days 1‐28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression. EAY191‐N5: Patients are randomized to 1 of 2 arms. ARM I: Patients receive neratinib maleate PO QD on days 1‐14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1‐28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study. ARM II: Patients receive neratinib maleate PO QD on days 1‐14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1‐28 and palbociclib PO QD on days 1‐21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

Nct (2022). "Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial." ClinicalTrails.gov.
	PRIMARY OBJECTIVES: I. Compare progression free survival of combination of olaparib and selumetinib sulfate (selumetinib) to selumetinib alone in patients with RAS mutant ovarian cancer. (Cohort 1) II. Compare progression free survival of combination of olaparib and selumetinib to selumetinib alone in patients with RAS mutant endometrial cancer. (Cohort 2) SECONDARY OBJECTIVES: I. Determine safety of both arms per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. II. Compare objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two arms. III. Determine rate of objective response per RECIST 1.1 in those patients that crossover from the single agent arm to the combination arm. IV. Report duration of response of the two treatment arms. V. Collect tissue and provide it to the ComboMATCH Registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre‐treatment biopsy mutation profile, and the pre‐treatment circulating tumor (ct)DNA mutation profile from plasma, as described in ComboMATCH Registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH Registration protocol. TRANSLATIONAL OBJECTIVE: I. To assess association of baseline genomic and transcriptomic status with response and resistance to therapy. OUTLINE: Patients in both cohorts are randomized to 1 of 2 arms. ARM I: Patients receive selumetinib orally (PO) twice daily (BID) and olaparib PO BID on days 1‐28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. ARM II: Patients receive selumetinib PO BID on days 1‐28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Nct (2022). "Tibial Nerve and Extracorporeal Magnetic Stimulation for Overactive Bladder." ClinicalTrails.gov.
	This study is a prospectively randomized, controlled trial. The trial will be held at Urogynecological Rehabilitation Unit of Pamukkale University, Physical Medicine and Rehabilitation Department between Nisan 2022 and October 2022. The local ethics committee approved the study (approvel no: 60116787‐020/59365). Participants will be informed about the purpose and contents of the study and all women give written consent to participate. By using a random number generator, all participants who include the study will be randomized into three groups as follows: The Group 1 will receive BT program alone, the Group 2 will be applied to BT plus TTNS, The Group 3 was applied to BT plus MStim. Group 1: BT ‐ Control group: All women will be informed about BT for 30 minutes. Then it will be given as a written brochure to be implemented as a home program. BT, consisting of four stages, will not contain any PFMT programs in anyone of three groups. Group 2: BT plus TTNS: Two self‐adhesive surface electrodes will be positioned according to the protocol previously used with the negative electrode 2 cm behind the medial malleolus and positive electrode 10 cm proximal. Correct positioning will be determined by noting a hallux reaction (plantar flexion of great toe or fanning of all toes). The stimulation protocol will be delivered at fixed 20 Hz and pulse width 200 ms in continous mode in accordance with the PTNS stimulation protocol. The intensity of the stimulation current (range 0‐50 mA) will be determined once correct positioning was established, according to the comfort level of the person. TTNS sessions will be performed twice a week for 6 weeks. Every session will be lasted 30 min. Treatment will consist of 12 sessions of stimulation. Group 3: BT plus MStim: Pariticipants will be told to sit on the chair with a magnetic coil below the chair. When a volume conductor is in serted by this magnetic field, an eddy current flow is generated. This eddy current stimulates nerve or muscle of the pelvic floor. To apply MStim, the device will be set to generate its maximum stimuli, with a stimulation pulse width of 200 μs and a stimulation repetition cycle of 10 Hz in accordance with the literature (10,13‐15). When setting the device at each treatment session, participants will be interviewed so that they'll receive stimuli at the maximum stimulation intensity (maximum tolerable stimulation intensity). MStim will be applied two days a week, 20 minutes a day, a total of 12 sessions for 6 weeks. MStim sessions will be performed by other physician.

Nct (2022). "Tinzaparin And Biomarkers After Neoadjuvant Treatment of Ovarian Cancer." ClinicalTrails.gov.
	This is an open randomized controlled clinical pilot trial (Phase II). The study includes women with the International Federation of Obstetrics and Gynecology (FIGO) stage III‐IV EOC selected for neoadjuvant chemotherapy (NACT) and without signs of thromboembolic disease or ongoing treatment of thromboembolic disease. The women will be allocated 1:1 to treatment with tinzaparin 4500 IU/8000 IU (dose depending on woman's weight) subcutaneously once daily or no tinzaparin. The treatment group starts tinzaparin when the primary treatment (chemotherapy) starts. The control group will not receive tinzaparin or other low molecular weight heparin preparations. The NACT consists of carboplatin and paclitaxel, given according to the standard regimen with cycle repeats every 21 days. Pre‐treatment, before every cycle of chemotherapy, before delayed primary debulking surgery (DPDS) and three weeks after the last cycle of chemotherapy venous blood samples will be taken for measuring the biomarkers hemoglobin, platelets, leucocytes, C‐reactive protein (CRP), albumin, cancer antigen‐125 (CA‐125), Tissue Factor, D‐dimer, soluble P‐selectin, thrombin‐antithrombin complex and thrombin generation potential. Furthermore, a panel of 92 inflammation‐associated proteins will be analyzed by a by a high‐sensitivity Proximity Extension Assay at baseline, visit 5 and visit 8 or 9. After three cycles of NACT, the patient will be evaluated clinically and with imaging diagnostics in order to determine whether the patient should undergo DPDS. In the investigators´ setting, > 80% of patients receiving NACT for EOC undergo DPDS. After DPDS, all patients will be treated with tinzaparin for 28 days according to clinical practice concerning postoperative thromboembolic prophylaxis and thereafter continue the chemotherapy for additional two‐three courses. The participants who were allocated to tinzaparin during the NACT will continue the tinzaparin after ending the postoperative thromboembolic prophylactic tinzaparin treatment for additional 2‐3 courses. The biomarkers will be measured preoperatively and four weeks postoperatively after DPDS and then before each course of chemotherapy given during the primary treatment. The women who do not undergo surgery will remain included in the study for the following three cycles of chemotherapy. Thus, the total study period constitutes 22‐29 weeks.

Nct (2022). "Tislelizumab Combined With Concurrent Chemoradiotherapy as First-line Treatment for Stage IIIC2 Cervical Cancer." ClinicalTrails.gov.
	This is a multicenter, prospective, and randomized phase II clinical trial. Patients assigned to experimental group will receive standard radiotherapy with concomitant cisplatin 40mg/m2 once every week for 5 weeks, combined with tislelizumab (200 mg, day 1) once every 3 weeks until disease progression or intolerable toxicity occurs or one year. Patients assigned to control group will undergo standard radiotherapy with concomitant cisplatin 40mg/m2 once every week for 5 weeks. Compare the efficacy and toxicity of the two regimens in patients with stage IIIC2 cervical cancer.

Nct (2022). "To Improve Depressive Symptoms Using a Web-App." ClinicalTrails.gov.
	This study is being done to answer a question on whether a Web App‐based Lifestyle Physical Activity Promotion Program is effective in improving depressive symptom experience of midlife Korean American women (WPAPP‐K). Korean American midlife women tend to suffer from depressive symptoms due to their menopausal transition, cultural background, age, and gender. The WPAPP‐K program that the investigators are testing is designed to help Korean American midlife women by providing information and coaching/support to increase lifestyle physical activity and subsequently improve their depressive symptom experience during the menopausal transition. The research team wants to know if the program improves depressive symptom experience of Korean American midlife women as designed.

Nct (2022). "Tolterodine Relieves Overactive Bladder Symptoms in Women With Moderate-to-severe Obstructive Sleep Apnea Syndrome." ClinicalTrails.gov.
	In this study, we aim to determine whether combined tolterodine and CPAP therapy is a more effective treatment for patients with OSAS than CPAP treatment only.

Nct (2022). "Topical Vaginal Estrogen for Postpartum Obstetric Anal Sphincter Injury Recovery." ClinicalTrails.gov.
	Obstetric anal sphincter injuries (OASIS) are known to cause significant morbidity and are known risk factors for sexual dysfunction, urinary and anal incontinence. Recent studies have reported that women with OASIS experience more problems with sexual dysfunction compared to their age and parity matched counterparts who do not have these tears. Despite this, little attention is paid to its prevalence or treatment in this population. These women are also at a 4‐fold higher risk of anal incontinence. Additionally, significantly more women with OASIS report urinary incontinence 10 weeks after delivery and have significantly worse quality of life scores. Postpartum and breastfeeding are relative hypoestrogenic states with risk factors for dyspareunia and vaginal atrophy. Estrogen deficiency results in changes in the vaginal epithelium and poor tissue quality which results in poor wound healing. For postmenopausal women with vaginal atrophy undergoing surgery for pelvic organ prolapse, early administration of topical vaginal E2 therapy resulted in improved markers of tissue quality. Due to the significant morbidity associated with OASIS, it is critical to further explore treatment options to ultimately improve wound healing and outcomes in women who sustain OASIS tears in their postpartum recovery. Training in identification of OASIS and close follow up in specialized OASIS clinics have improved outcomes for these women. However, there are limited studies to reference for proposed treatment modalities to improve sexual function and incontinence in this population. Intra‐vaginal estrogen therapy has proven to be safe and feasible in this population as demonstrated by no difference in the serum estrogen concentration in those women treated with intra‐vaginal estrogen therapy for treatment of granulation tissue. Although evidence is limited, anecdotally, vaginal estrogen cream has been used to treat postpartum women with OASIS to treat vaginal atrophy and improve wound healing. This proposed research is critical to ultimately improving the postpartum recovery for women who sustain OASIS. This information will add to the growing literature aiming to optimize quality of life and improve care for these women. In this proposed randomized, placebo‐controlled trial, women who sustain OASIS will be recruited and randomized to begin intravaginal estrogen therapy or placebo at their 2‐week follow‐up visit, (upon establishing care at postpartum perineal clinic), after hospital discharge. Participants will complete validated questionnaires relating to sexual function and pelvic floor disorders (urinary and anal incontinence) symptom distress and impact at the 2‐week postpartum visit (baseline). Participants will follow up at designated intervals (12‐weeks and 6 months) and complete questionnaires with plan for total of 6‐months intravaginal estrogen or placebo therapy. The primary outcome will be sexual dysfunction symptom severity measured by the female sexual function index (FSFI) at 6 months postpartum. Secondary outcomes will be urinary and anal incontinence distress and impact measured by St. Mark's and the fecal incontinence quality of life (FIQOL) scores for anal incontinence and urogenital distress inventory (UDI‐6) for urinary incontinence. The objective of this study is to determine if intra‐vaginal estrogen therapy improves sexual function and incontinence symptom distress and impact for postpartum women after OASIS. We hypothesize that topical vaginal estrogen cream therapy postpartum will improve sexual function scores thereby improving functional status and related quality of life.

Nct (2022). "Traditional Vaginal Surgery VS Autologous Tissue in Pelvic Floor Repair." ClinicalTrails.gov.
	All patients will be operated by the same surgeon. Antibiotic prophylaxis will be given pre‐operatively according hospital protocols 30 minute before surgery. Surgery will be performed under general anesthesia in the lithotomy position with legs in stirrups The following peri‐operative and patient data will be collected and analyzed: preoperative POP‐ Q, body mass index (BMI), age, parity, history of vaginal delivery, previous pelvic surgery, total operating time, estimated bloodloss, serum hemoglobin (Hb) drop (change between preoperative Hb and postoperative Hb 1 day after surgery), peri‐operative complications, post‐ operative pain score and POP‐Q after 6 and 12 months. The ICIQ‐LUTSqol questionnaire (International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life Module) is a psychometrically robust patient‐ completed questionnaire evaluating quality of life (QoL) in urinary incontinent patients with particular reference to social effects. It has 20 items to response with overall score between 19‐ 76 indicating increased impact on quality of life with greater values. Subjective surgical outcome was measured using the Patient Global Impression of Improvement (PGI‐I), which is a validated tool as a global index of response to prolapse surgery. The PGI‐I is a seven‐scale response for women comparing the postoperative condition with the pre‐operative state, 1 being very much better and 7 being very much worse. The women's prolapse symptoms and their impact will be evaluated before surgical treatment. A subjective assessment of the prolapse was made using Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA revised (PISQ‐IR) before and 12 months after treatment. The PISQ‐IR is designed as a condition‐specific measure of sexual function in women with pelvic floor dysfunction, including urinary and anal incontinence and pelvic organ prolapse. It consists on 18‐21 questions depending weather respondent indicates having a sexual partner or not. The cutoff score of 2.68 for PISQ‐IR Summary Score allowed to diagnose sexual dysfunction in sexually active women with pelvic floor disorders. Pelvic floor ultrasound will be performed before the operation and at 6 and 12 months after the operation. The inspection methods are as follows: Before the inspection, patients emptied the stool and moderately filled the bladder. The following parameters will be measured in resting state using the maximal Valsalva maneuver: Posterior vesicourethral angle (PVA):This included the angle between the proximal urethra and posterior wall of the bladder. Urethral tilt angle: This included the angle between the proximal urethra and vertical axis of the human body. Value is negative if the urethral axis deviated to the ventral side, and the value was positive when it is deviated to the dorsal side. Postoperative rotation angle of the urethra (UR): This refers to the difference in PVA between the Valsalva state and resting state. Bladder neck descent (BND): This refers to the vertical displacement of the bladder neck between the Valsalva state and resting state.

Nct (2022). "Transcranial Direct Current Stimulation to Reduce Chronic Pelvic Pain in Endometriosis." ClinicalTrails.gov.
	In the study it will be tested whether transcranial direct current stimulation can reduce the perception of pelvic pain in patients with endometriosis. Hypothesis: Transcranial direct current stimulation can reduce the perception of pelvic pain in patients with patients with endometriosis.

Nct (2022). "Transformatıonal Learnıng Theory on Infertılıty and Stigma in Infertılıty Women." ClinicalTrails.gov.
	Nurses have important duties in providing counseling and support to infertile individuals during this crisis, which is very difficult to cope with. In this context, nurses should provide psychosocial care that will enable the individual to accept and cope with the current process. This study will be conducted to evaluate the effect of the education program created according to the transformational learning theory on women being affected by infertility and feeling stigmatized due to infertility. The study was planned as a single‐center parallel group simple randomized controlled trial. The population of the study will be women who applied to Tatvan Maternity and Children's Hospital due to infertility between 22/05/2022‐22/05/2023. Power analysis was performed to determine the number of samples. For this, the information in a similar study (Infertility Stigma Scale Experiment Mean: 38.67±4.75, Control Mean: 69.76±4.5) was used as a reference. Analysis was done in G power version 3.1. The minimum number of participants required to be included in each group was determined as 22, with a total of 44 (α=0.05, 1‐β=0.95). However, considering the loss rate (21.77%) in the reference study, the total number of participants was increased by 20% to 52 (experimental: 26, control: 26). Personal Information Form, Infertility Affected Scale and Infertility Stigma (Stigma) Scale will be used to collect data. Application First of all, the aim and content of the research will be explained to the women. Their compliance with the sampling inclusion criteria will be evaluated. Afterwards, women who agreed to participate in the study will have an informed consent form signed. Personal information form and pre‐tests (Infertility Affect Scale and Infertility Stigma Scale) will be applied to women. Then, the women will be randomly randomized to assign the experimental and control groups. Contact information (Phone numbers and e‐mail addresses) will be taken at the first encounter. Experimental Group Application A training program consisting of four modules created according to Transformational Learning Theory will be applied once a week to the women in the experimental group by forming groups of 3‐10 people. Post‐tests (Infertility Affect Scale and Infertility Stigma Scale) will be applied within 1 week after the training is over and in the 4th week after that. The training modules and the training methods to be used in the modules are given below: Module 1: Infertility Based on Gender Patterns: Meaning structures of "femininity", "motherhood" and "infertility" in society Dating activity, brainstorming, discussion over experiences, critical reflection Module 2: Violence due to infertility (The Concept of Stigma): Domestic and Social Pressure/Violence Introductory activity, role‐play, sharing feelings, discussion over experiences, critical reflection Module 3: Punishment and exposure to traditional practices for infertility Introductory activity, watching the movie, interpreting the movie through experiences, critical reflection Module 4: Interpreting the awareness experienced in the education process and sharing future plans Introductory activity, presentation (by women), peer review Control group application The post‐tests (Infertility Affect Scale and Infertility Stigma Scale) will be applied to the women in the control group 5 weeks after the pre‐test application and 4 weeks after this application.

Nct (2022). "Transversus Abdominis and Pelvic Floor Muscle Strengthening Exercise Program In Patients With Grade 1 Cystocele." ClinicalTrails.gov.
	Cystocele, in any other case called a protrusion of the bladder, happens while the bladder descends into the vagina.The bladder bulges via the anterior wall of the vagina, with which it's miles anatomically related. There are more than one underlying causes for the development of cystocele ensuing in weak point of the muscles and the connective tissue surrounding the bladder and vagina. This study will be a randomized clinical trial. After the department permission of physical therapy data will be collected from patient of Jinnah Hospital. Data will be collected before and after treatment. Total sample size is 60. Non probability convenient sampling technique will be used. Randomization will be done by lottery method. Group A will be given pelvic floor strengthning exercises and goup B will be given transverse abdominas strengthning exercises. Each group will have 33 patients each. A 6‐week physical therapy program will be planned. Group A will be given pelvic floor muscle strengthning exercise and the group B will given transverse abdominas exercises. Individual sessions will be held twice a week for 60 minutes each. Each meeting will include a theoretical portion of up to 10 minutes and a practical portion of roughly 50 minutes. Home plan will also be shared with them. Post treatment analysis will be done in order to find the effects of both regims. Data will be entered and analysed by SPSS version 25. The aim is to compare the effects of transversus abdominis and pelvic floor muscle strengthening exercise program on disability and urinary incontinence in patients with grade 1 cystocele.

Nct (2022). "TReating Incontinence for Underlying Mental and Physical Health." ClinicalTrails.gov.
	The TRIUMPH study is a randomized, double‐blinded, 3‐arm, parallel‐group trial designed to compare the effects of anticholinergic bladder therapy versus a) beta‐3‐adrenergic agonist bladder therapy and b) no bladder pharmacotherapy on cognitive, urinary, and other aging‐related functional outcomes in ambulatory older women with urgency‐predominant urinary incontinence and either normal or mildly impaired cognitive function at baseline.

Nct (2022). "Treatment for Antepartum Posttraumatic Stress Disorder/PTSD Study." ClinicalTrails.gov.
	Pregnant women with posttraumatic stress disorder (PTSD) are at increased risk for adverse pregnancy outcomes, yet the majority of pregnant women with mental health needs do not receive treatment, with disparities in treatment utilization among low‐income and racial and ethnic minority women. Perinatal mental health treatment gaps are foremost a consequence of behavioral health workforce shortages and a lack of data on PTSD treatment during pregnancy. Mental health stigma and medical mistrust due to racism further impact engagement in care. Written Exposure Therapy (WET) is a brief 5‐session PTSD treatment that was designed to address the capacity‐limiting concerns of first‐line treatments (e.g., time burden of training and delivery). WET has demonstrated non‐inferiority (and fewer dropouts) when compared to first‐line PTSD treatments. As such, the empirical support and implementation advantages of WET suggest the promise of this intervention in addressing PTSD among pregnant women seen in usual care obstetrics settings. Training non‐mental health specialists, such as community health workers (CHWs), to deliver WET may dually address workforce capacity challenges and patient engagement factors such as stigma. The objective of this research is to conduct a randomized controlled trial to examine both the effectiveness of WET for treatment of PTSD during pregnancy against an active control condition [i.e., emotion focused supportive therapy (EFST)] and the non‐inferiority of WET delivery with a community health worker (CHW‐WET) vs. WET delivery with a mental health clinician. A total of 240 pregnant women with PTSD receiving obstetrical care at Boston Medical Center (BMC), a large safety net hospital that cares for a racially and ethnically diverse population, will be recruited. Following a baseline visit, women will be randomized to either CHW‐WET (N=80), standard WET (N=80), or EFST (N=80). Participants in either WET condition will receive 5 individual sessions focused on the use of writing to activate the trauma memory, process emotions, and make meaning. EFST participants will receive 5 individual sessions of supportive therapy. Participants will complete well‐established measures of PTSD and other psychological symptoms (e.g., depression) and proposed moderators of treatment engagement at baseline, post‐treatment, and 1‐, 6‐, and 12‐months postpartum. Patients and providers will also complete measures and interviews following treatment to assess feasibility, acceptability, and appropriateness of the WET delivery approaches in a usual care setting. Aim 1 is to determine if a) CHW‐WET is non‐inferior to standard WET and b) CHW‐WET has better retention than standard WET. Aim 2 is to demonstrate the effectiveness of WET for treatment of PTSD (vs. EFST) in an obstetrics setting. Exploratory Aim 3 will examine moderators of treatment engagement such as mental health stigma to inform a personalized approach to WET treatment delivery. Aim 4 is to conduct a process evaluation of the WET delivery approaches. This study will inform future efforts to improve access to and quality of care for treatment of PTSD during pregnancy.

Nct (2022). "Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes." ClinicalTrails.gov.
	The primary purpose of this study was to evaluate the effect of ESN364 on the severity and frequency of hot flashes in early postmenopausal women suffering from hot flashes, in terms of changes in weekly Hot Flash Score from baseline to Week 12. This study also evaluated the effect of ESN364 on the severity and frequency of hot flashes at additional timepoints; hot flash interference on daily life, in terms of changes from baseline over time in Hot Flash Related Daily Interference Scale (HFRDIS); the effect of ESN364 on climacteric symptoms, in terms of changes from baseline over time in Leeds Sleep Evaluation Questionnaire (LSEQ), Greene Climacteric Scale (GCS), and Sheehan Disability Scale (SDS); pharmacodynamic (PD) effect; and safety and tolerability.

Nct (2022). "Trigger Point Treatment in Chronic Pelvic Pain." ClinicalTrails.gov.
	Chronic pelvic pain (CPP) is chronic or persistent pain perceived in structures related to the pelvic region. CPP prevalence range between 5.7 % and 26.6 % in women. CPP is associated with symptoms suggestive of the lower urinary tract, sexual, bowel, pelvic floor, or gynecological dysfunction. It is often associated with negative emotional consequences and impaired quality of life (QoL) Analgesics, hormone therapy, physiotherapy, psychological treatment, and surgical methods are widely used in the treatment of CPP. Medications provide pain and visceral management, surgery provides correction of structure, but physiotherapy approachs provides functional restoration. Musculoskeletal pelvic pain is commonly originated myofascial, musculoskeletal, neuromuscular structures. CPP patients have myofascial trigger points (MTrPs) located in the lower back, abdominal wall, and pelvic girdle, which may be the primary source of pain. These MTrPs are usually located in levator ani, obturator internus, piriformis, gluteal muscles, quadratus lumborum and abdominal wall muscles. The MTrPs are hyperirritable spots within a taut band, activated by repeated or chronic muscular overload. Ischemic compression (IC), in the other words trigger point compression, is an effective method in the treatment of MTrPs in many musculoskeletal problems. IC changes the circulatory perfusion of skin and is especially valuable in muscles that are not suitable for stretch. It is less common to use pelvic floor rehabilitation, urological CPP, interstitial cystitis and painful bladder syndrome and CPP yet. Low‐level laser therapy (LLLT) reduces pain in MTrPs lead to musculoskeletal system disorders. LLLT increases oxygen supply to hypoxic cells in MTrPs areas by regulating microcirculation as well as it has analgesic, biostimulation, and wound healing effects . In the literature, it is seen that IC and LLLT are effective on MTrPs, and IC is used in pelvic pain in a few studies. But the use of LLLT in pelvic pain has not been found. It is a known fact that exercise is the basis for these MTrPs treatments. In light of this knowledge, investigetors hypothesized that both IC and LLLT combined with exercise would be an effective methods in the management of CPP.

Nct (2022). "Triple Antiemetic Regimen for Chemoradiotherapy in Cervical Cancer or Nasopharyngeal Cancer." ClinicalTrails.gov.
	The study was designed as a prospective,randomized, single‐blind control clinical trial aiming to assess the efficacy and safety of fosaprepitant combined with tropisetron and dexamethasone in preventing nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly low‐dose cisplatin chemotherapy in patients with cervical cancer or nasopharyngeal cancer.

Nct (2022). "Use of Nitrous Oxide for Pain Alleviation in Women Undergoing Osmotic Dilator Insertion for Dilatation and Evacuation." ClinicalTrails.gov.
	Introduction: Women undergoing second trimester abortion often undergo preparation of the cervix prior to the Dilatation and Evacuation (D&E). Women may undergo preparation with osmotic dilators (laminaria) or prostaglandins, both methods are effective and safe for cervical preparation(1). In our institution, the protocol for cervical preparation in the second trimester with osmotic dilator insertion takes place 24 hours before the procedure in the gynecologic emergency room/clinic. Currently, the protocol does not include any method of pain relief during the cervix preparation procedure. At this time, besides general anesthesia, there are no satisfactory evidence‐based methods for pain alleviation for osmotic dilators insertion. For example, a recent randomized controlled trial showed topical application of lidocaine spray to the cervix before insertion did not result in lower reported pain as compared with placebo(2). Inhaled nitrous oxide administered with oxygen (N2O/O2) is an acceptable, effective and widely used method for pain relief in short painful pediatric ,dental and urologic procedures(3‐5), as well as in the labor room and in the emergency room(6, 7). N2O/O2 has analgesic, anxiolytic and amnestic properties. N2O/O2 has rapid onset and reversal with minimal side effects and few contraindications. Side effects of N2O/O2 are relatively minor and include nausea, dizziness, drowsiness, light‐headedness, and diaphoresis. Contraindications include congenital heart defects, pulmonary hypertension, megaloblastic anemia and relatively low blood O2 saturation (<95%)(8, 9). A recent randomized controlled trial showed inhaled N2O/O2 is associated with less pain compared to oral sedation for pain management during in‐office hysteroscopic sterilization(9) To the best of our knowledge, there is no literature regarding the efficacy of use of nitrous oxide for pain alleviation in women undergoing osmotic dilator insertion for second trimester Dilatation and Evacuation. Goal: To examine whether inhaled N2O/O2 during cervical preparation for second trimester dilatation and evacuation alleviates pain and is superior to placebo. Methods: A prospective randomized placebo‐controlled trial consisting of two groups: Inhaled N2O/O2 (group 1) Placebo group (O2 only) (group 2) Women undergoing dilatation and evacuation in the second trimester and are about to undergo cervical dilatation with osmotic dilators (laminaria) will be invited to participate in a randomized placebo control trial comparing Inhaled N2O/O2 or placebo (O2 only). The recruitment and trial will take place in the emergency room/clinic where the women come a day before the D&E for cervical preparation. This procedure is routinely performed in a gynecologic chair without any sedation thus assessing pain scores is possible. Informed consent will be obtained from each participant. Randomization will be performed using a computer randomization generator. After enrollment, patients will be randomized into one of the two study arms. allocation to the two treatment groups will be concealed in sequentially numbered opaque envelopes that will be opened only by the nurse actually administering the gas (either inhaled N2O/O2 or inhaled oxygen). The participant and physician will be completely blinded to the intervention. Participants will be asked about their most severe pain during menses and asked to rate it from 0 to 10. The patient will be placed in the lithotomy position. Group1: Patients will receive inhaled N2O/O2 (70% N2O and 30% O2). A sterile bivalve speculum will be placed. Laminaria will be inserted. Inhaled N2O/O2 will be stopped after speculum removal. Group2: Patients will receive inhaled O2 (100% O2). A sterile bivalve speculum will be placed. Laminaria will be inserted. Inhaled O2 will be stopped after speculum removal. Patients will receive inhaled O2 (100% O2) throughout the procedure until speculum removal. Pain will be assessed at 7‐time intervals using a visual analog pain scale 0 (no pain) to 100 (worst possible pain) ‐ 1.Prior to mask pplication, 2. Before speculum insertion, 3. Immediately after speculum insertion, 4. Immediately after insertion of first laminaria, 5. Immediately after insertion of last laminaria, 6. After speculum removal (including actual VAS and recall of maximal VAS during the procedure), 7. Before the D&E the next day. Satisfaction with the procedure will be collected as well‐ overall satisfaction (0‐100) and satisfaction with pain control (0‐100). Data regarding adverse events will be collected as well. Primary outcome: Self‐report of pain score immediately following speculum removal. Secondary outcome: Self‐report of maximal pain during the procedure. The protocol will not be repeated if a participant is to return for further laminaria insertion.

Nct (2022). "The Using Postoperative Ketamine and Exploring the Effect on Endometriosis Pain (UPKEEEP) Study." ClinicalTrails.gov.
	This is a randomized, single blinded, placebo‐controlled trial to study the effectiveness of a subanesthetic dose (0.6 mg/kg) of ketamine versus placebo (saline) on postoperative pain and pain on adult female chronic pelvic pain patients undergoing robotic removal of endometriosis. The objective of the study is to explore the effect of a sub anesthetic dose of ketamine (0.6 mg/kg) vs. saline control on postoperative pain and recovery in chronic pelvic pain patients who have undergone robotic removal of endometriosis.

Nct (2022). "Value of Follicular Flushing. Randomised Controlled Trial." ClinicalTrails.gov.
	There is an ongoing debate regarding the effectiveness of follicular flushing during oocyte retrieval. Currently published studies and metanalyses suggest that follicular flushing does not improve live birth rate, clinical pregnancy rate or the number of oocytes retrieved. However, currently published studies may be confounded by the types of needle used, aspiration pressures, number of times flushing is repeated, etc. Additionally, follicular flushing should be examined in specific patient populations according to their response to ovarian stimulation. In the current study, each woman will have one ovary (right or left) randomly assigned to be aspirated with or without the addition of follicular flushing. This study design ensures that clinical and demographic characteristics of the couple will not affect the outcomes evaluated. The primary endpoints will be the number of oocytes retrieved per ovary assigned to each group. Secondary outcomes will be the oocyte recovery rate (oocytes retrieved per follicle aspirated) oocyte maturation rate, fertilization rate, and embryo development per ovary assigned to each group. The study population will include three subgroups according to observed ovarian response to ovarian stimulation (poor responders, normal responders, hyper responders). Assuming a minimum clinically significant difference in oocyte yield of 1 oocyte, a sample size of twenty patients per subgroup is required to yield 80% power. Patients aged <43 years with the presence of at least one follicles >11mm in each ovary on the day of triggering final oocyte maturation will be eligible for inclusion in the study. 60 patients (20 in each of the aforementioned subgroup) will be recruited and just prior to oocyte retrieval their left and right ovaries will be randomly allocated into flushing or the no‐flushing group. In both ovaries all follicles greater than 11mm will be punctured by the same 16G double lumen needle, using the same aspiration pressure. In the flushing group, flushing will be performed up to a maximum of five times or until a cumulus oocyte complex (COC) is retrieved. In the control group all follicles greater than 11mm will be aspirated by the same double lumen needle and no flushing will be performed. All COCs will be grouped according to the ovary they originated from by the embryologists and their development will be recorded until Day 3 following fertilization (Number of MII oocytes, number of fertilized oocytes, number good quality Day 3 embryos).

Nct (2022). "Virtual Reality to Improve Low-back Pain and Pelvic Pain During Pregnancy." ClinicalTrails.gov.
	A large percentage of women suffer low back and pelvic pain both during and after pregnancy. There are several factors to which these complaints are attributed, even affecting their daily lives. It is identified that many of these women do not receive adequate health care, however, different physiotherapeutic interventions are recommended to alleviate these conditions, presenting moderate levels of evidence. Virtual reality (VR) is presented as a complementary and promising treatment method to physiotherapy for the improvement of fundamental variables such as perceived pain and pain avoidance. The main objective is to evaluate the efficacy of a combined VR and physiotherapy program of 4 weeks duration compared to a standard physiotherapy intervention in pregnant women with low back pain and pelvic pain for the improvement of pain avoidance, pain intensity, disability and functional level. As a secondary objective the investigators propose to investigate patient satisfaction with the VR intervention. This research will be carried out by means of a multicenter randomized controlled clinical trial in pregnant patients residing in the provinces of Seville and Malaga with a diagnosis of low back pain and pelvic pain during pregnancy. The alternative hypothesis of this research is that the implementation of a Virtual Reality program together with standard physiotherapy in pregnant patients with low back and pelvic pain presents better clinical results obtained with the current standard intervention, which may represent an opportunity to define new policies and interventions for these pathologies and their consequences.

Nct (2022). "Vırtual Reality, Music Therapy and Stress Ball-related Pain and Anxiety." ClinicalTrails.gov.
	Virtual Reality Virtual Reality (VR) is a term formed from the words virtual and reality. According to the Turkish Language Association; Virtuality, which means unreal, or hypothetical, derives from the Latin word "virtual". The reality is; the real is defined as the whole of the things that exist and the truth. Virtual reality, which emerged as a concept in the 1950s, started to be used in application areas in the 1900s. Virtual reality, which has been used only for space and military research as a computer‐based, high‐cost technology for years, has recently become widespread in the fields of medicine, education, entertainment, librarianship, museology, architecture, and industrial design with different applications developed for mobile devices. Today, common and easily accessible android‐based smart devices capable of running virtual reality are used. The image is obtained using a combination of framed simple optical lenses that hold the phone at a fixed distance perpendicular to the user's gaze direction. The working system of three‐dimensional resuscitation devices is based on stereographic vision properties. After the relevant applications are installed on the smartphone, the device divides the screen into two, and thanks to the acquisition of different images for the right and left eyes, the illusion of the spatial existence of three‐dimensional animated objects is obtained. Virtual Reality is a simulation model that gives a sense of reality to its participants, is created based on computers, and allows mutual communication. Virtual Reality Application in Pain and Anxiety Management Virtual reality, which is a type of computer system using human‐machine interfaces, has been used in the management of pain and anxiety in many different applications known as painful medical procedures in recent years. According to the researchers' hypotheses, virtual reality; acts as a non‐pharmacological method using cognitive and attentional processes on the body's complex pain modulation system. Although its neurobiological mechanisms have not been fully explained, studies have interestingly reported that it brings positive results in pain management. In virtual reality applications, patients feel that they are in the image, their attention is effectively distracted from the pain, and the perception of pain is reduced. In recent years, virtual reality as a distraction application; It is used in the management of pain and anxiety in procedures such as burn debridement, injection applications, wound care, toothache, endoscopy procedure, phantom, and chronic pain, and chemotherapy applications. Music Therapy in Pain and Anxiety Management Music therapy is a method that has been used frequently among complementary and alternative medicine applications for centuries. Music, which consists of regular, harmonious rhythms and sounds that we hear with our ears, is a behavior that expresses the aesthetics found in human nature. The therapeutic use of music has an active role in making people feel and communicate with their emotional dimension. The first scientific theorist of the use of music therapy in treatment was Pythagoras. Today, a quintuple scale system is known as the 'Pythagorean Scale' or the 'Fiddler Scale'. For the ancient Greeks, music is considered the most basic element of spiritual education and purification of the soul from evil. Athennoaops aimed to alleviate the pain by playing an instrument in the area of pain by using the vibration effect. In Turkish‐Islamic Civilization; According to great philosophers and scientists such as İbn‐i Sina and Farabi, music not only improves the hearing power, but also the cognitive ability of people with the suggestions it creates. Music was also used in the treatment of mental illnesses with the melodies made by the Sufis who were dealing with Sufi music. XV‐XVI. between the Kayseri Gevher Nesibe Medical Madrasa and Edirne Sultan II. The architecture of Ottoman‐era hospitals such as the Bayezid Hospital was built in accordance with the isolation of patients, e tilation, and treatment with music. Today, the effectiveness of music therapy as a complementary medicine application has been proven in many studies. American Music Therapy Association; reported that music significantly reduced pain and anxiety levels. There are studies stating that music is effective in pain during burn dressing and cancer‐related pain, reduces opioid use after surgery, reduces the stress levels of patients during childbirth and different medical applications, and decreases blood pressure and pulse values. music therapy; By focusing the patients on the rhythm of the music, distracts their attention from the pain, and activating the door control system, reduces the perception of pain. Music therapy increases the secretion of endorphins and relaxes the individual. music therapy; is used in the treatment of pain and anxiety as a non‐pharmacological method that is easy to apply, economical, and has no side effects. Stress Ball in Pain and Anxiety Management A stress ball is a simple, reliable, inexpensive, and easily accessible method that helps reduce the anxiety of patients. It is stated that the use of stress balls generally relieves patients. A stress ball, which is one of the distraction methods, is also an effective method in providing cognitive focus. It is seen in studies that stress ball application is used to reduce the anxiety and pain of patients. Squeezing a stress ball during the surgical procedure allows patients to have direct control over the object in their palm and increases patients' feelings of empowerment. Applying a stress ball in this way has a positive effect on anxiety and patient satisfaction without interfering with the surgical procedure. In another study; It has been found that holding a stress ball reduces both pain and anxiety in patients undergoing surgical procedures. In the study of Yanes et al. to evaluate the effects of a stress ball or hand holding on pain, anxiety, and satisfaction in skin cancer surgery performed under local anesthesia, it was concluded that anxiety decreased in all groups. In the study, it was concluded that the stress ball helped reduce anxiety in patients who were anxious before the procedure. In the study conducted by Kasar et al. on hemodialysis patients, it was concluded that the use of a stress ball has a positive effect on stress. In the study conducted to determine the effect of distraction methods used during the cystoscopy procedure on pain, anxiety, and satisfaction, it was concluded that the level of post‐procedural anxiety was lower in the intervention groups (music, video, and stress ball) than the control group, and the satisfaction was higher. In a randomized controlled study in which three different non‐pharmacological methods (coughing technique, spirometer blowing, and stress ball squeezing) were evaluated in reducing pain during intravenous catheterization; It was concluded that the pain averages of the patients in the coughing technique, spirometer blowing and stress ball groups were lower than the control group. In another study examining the effectiveness of distraction methods for pain and anxiety management during invasive venous surgery, it was concluded that pain and anxiety were significantly lower in the interaction with nurses and the stress ball group.

Nct (2022). "Virtual Visits for Postoperative Care Following Urogynecologic Surgery." ClinicalTrails.gov.
	The study is a randomized controlled trial evaluating patient satisfaction with in‐office versus virtual‐video postoperative visits at six weeks following urogynecologic surgery. The investigators aim to assess whether the intervention of virtual postoperative visit via videoconference technology is similar to the standard/traditional in‐office postoperative visit for our primary outcome of patient satisfaction. The follow‐up period for each participant will be 12 weeks after surgery. The investigators will recruit patients of the Center for Urogynecology and Pelvic Reconstructive Surgery in the Department of Obstetrics/Gynecology and Women's Health Institute at the Cleveland Clinic scheduled to undergo major or minor surgery for pelvic organ prolapse and/or urinary incontinence. Participants will be prospectively identified by the primary surgeon during the patient's initial consultation when the decision is made to proceed with surgery for pelvic organ prolapse and/or urinary incontinence. Enrolled participants will be randomized to either the office visit arm or the virtual visit arm. Stratified block randomization will be used to ensure that the number of participants is equally distributed among the study groups and stratified by surgery level (major, minor). Study instruments will be administered at the preoperative visit and the 6‐week postoperative visit. The questionnaires for this study include the Patient Preparedness Questionnaire (PPQ), the Patient Satisfaction Questionnaire‐18 (PSQ‐18), and modified patient and provider preference questionnaires entitled, Patient Postoperative Visit Questionnaire and Provider Postoperative Visit Preference Questionnaire. In addition to questionnaire responses, the investigators will collect the following information from the electronic medical record: Demographic data (e.g. age, race, parity, body mass index), perioperative data (e.g. surgery level major/minor, surgery type, concomitant procedures, estimated blood loss, operative time), six‐week postoperative data (e.g. route of postoperative visit in‐office/virtual, patient‐initiated phone calls to surgeon's office, unanticipated outpatient visits, emergency department visits, hospital readmissions prior to 6‐week visit, adverse events prior to postoperative visit), and twelve‐week postoperative data (e.g. patient‐initiated phone calls to surgeon's office, unanticipated outpatient visits, emergency department visits, hospital readmissions prior to 6‐week visit, adverse events prior to postoperative visit). Power analysis is based on a randomized controlled study by Lee et al., which demonstrated a mean PSQ‐18 score of 81.2 ± 2.8 in patients who had an in‐person/office visit with the physician at approximately 30 days following their surgery. Assuming a SD=3, 74 patients will be needed to detect a difference of 2 points on the PSQ‐18 between the office and virtual groups using t‐test at a significance level of 0.05 and a power of 80%. To account for an attrition rate of 10%, a total of 82 participants will be needed for this study, with 41 women in the intervention arm and 41 women in the control arm. For the analysis plan, approximately normally‐distributed continuous measures will be summarized using means and standard deviations and will be compared using two‐sample t‐tests. Continuous measures that show departure from normality and ordinal measures will be summarized using medians and quartiles and will be compared using Wilcoxon rank sum tests. Categorical factors will be summarized using frequencies and percentages and will be compared using Pearson's chi‐square tests or Fisher's Exact tests. All analyses will be conducted with an a priori alpha level of 0.05; results yielding a p‐value of less than 0.05 are deemed statistically significant. Data will be managed in REDCap and analyzed using the SAS 9.4 statistical package.

Nct (2022). "What is the Best Moment for Performing an HSG in Women With a Unfulfilled Childwish." ClinicalTrails.gov.
	Rationale: The investigators hypothesize that direct tubal flushing with oil‐based contrast at HSG incorporated in the fertility work‐up results in 10% more ongoing pregnancies and a shorter time to pregnancy compared to delayed tubal flushing 6 months after fertility work‐up is completed in women at low risk for tubal pathology, which will lead to a reduction in the need for expensive fertility treatments like IVF and/or ICSI, and will therefore be an effective and cost effective strategy. Objective: The aim of this study is to determine whether direct tubal flushing with oil‐based contrast at HSG incorporated in the fertility work‐up results in 10% more ongoing pregnancies and a shorter time to pregnancy, which will therefore be effective and cost‐effective compared to delayed tubal flushing 6 months after fertility work‐up is completed in women at low risk for tubal pathology. Study design: The investigators plan a multicentre randomized controlled trial with an economic analysis alongside it. Infertile women at low risk for tubal pathology will be randomized to direct tubal flushing with oil‐based contrast incorporated in the fertility work‐up or delayed tubal flushing 6 months after fertility work‐up is completed. Study population: Infertile women 18‐38 years of age, who have a spontaneous menstrual cycle and at low risk for tubal pathology, undergoing fertility work‐up. Intervention (if applicable): Direct tubal flushing with oil‐based contrast at HSG as part of the fertility work‐up compared to delayed tubal flushing 6 months after the fertility work‐up is completed. Main study parameters/endpoints: The primary outcome is time to live birth, calculated from positive pregnancy test and within 12 months after randomization. Our hypothesis is that tubal flushing at HSG with oil‐based contrast incorporated in the fertility work‐up will result in 10% more ongoing pregnancies and a shorter time to pregnancy, and thus reducing the need for ART and reducing costs. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: As two strategies are compared (tubal flushing with oil‐based contrast at HSG incorporated in the fertility work‐up versus 6 months after completion of fertility work‐up) that are already applied in current practice, no additional risks or burdens are expected from the study.

Nct (2022). "Wrist Cooling for Hot Flashes Clinical Trial." ClinicalTrails.gov.
	The randomized group will determine the order that a participant uses each device. Group 1 participants will use the wrist cooling device first for two weeks and then the fan activating device for two weeks. Group 2 participants will use the fan activating device first for two weeks followed by the wrist cooling device for two weeks. This will be a 6 week study requiring the participants to see a study team member at the beginning of the study. The participants will receive three phone calls during the study to remind them of when to use each device. They will be instructed after the 6 weeks for them to have an in person return visit and give the diaries and the devices to the study personnel. The investigators will recruit participants and conduct the study at the Boston University School of Medicine (BUSM), locally, and virtually.

Nct (2023). "4-week Seaweed Supplementation on Menopause Symptoms and Psychological Wellbeing." ClinicalTrails.gov.
	Menopause and peri‐menopause are associated with a number of symptoms and psychological well‐being. Previous literature has found a relationship between diet and menopause management. For example, following the Mediterranean diet consuming a variety of vegetables, fruits, legumes and whole grains has found to improve menopausal symptoms particularly vasomotor symptoms. Few studies have explored the effects of dietary supplements on psychological well‐being in menopause. The aim of the study is to explore the impact of an iodine‐rich seaweed food supplement on menopause symptoms and mental well‐being in those experiencing menopause. Online assessments of symptoms will take place pre‐intervention and post‐intervention and will be compared to the effects of a placebo.

Nct (2023). "Abdominal-Kegel Exercise and the Effect of Telemedicine in Stress Urinary Incontinence." ClinicalTrails.gov.
	The study is a randomized controlled study to be conducted in female patients between the ages of 20‐65 who applied to the Eskişehir City Hospital urology outpatient clinic and diagnosed with stress urinary incontinence. When type 1 (α) error was 5%, type 2 error (1‐β) was 95%, and the effect size was accepted as 0.5, it was calculated that there should be at least 47 people in the groups. Stratified and block randomization will be used to recruit patients into study groups. The patients will be evaluated with the QUID test, risk assessment questionnaire in patients with stress urinary incontinence, incontinence short test, bladder diary, daily urinary incontinence, a notebook to record the duration of the exercises to be performed, quality of life scale and lifestyle changes questioning form. The intervention group will be re‐evaluated as a result of the intervention with measurement tools. Intervention group: Brochure about incontinence will be given, web‐based training will be applied, SMS will be sent every day according to the risks. Control group: Only brochure will be given. It is expected that a low‐cost application to be developed after the study will reduce the complaints of the patients, increase their quality of life and have a positive effect on women's health. It is difficult for physicians to allocate sufficient time to convey lifestyle changes and exercises to patients with stress urinary incontinence during their busy work hours in the clinic. After the success to be achieved, the usage rate of the website to be prepared will be increased through various scientific platforms and associations.

Nct (2023). "Acupuncture Combined With Mirabegron in the Treatment of OAB." ClinicalTrails.gov.
	Introduction: As conventional treatments for overactive bladder (OAB) have not yet shown satisfactory results, new approaches are needed. Therefore, this study aimed to investigate the efficacy and safety of acupuncture combined with mirabegron for the treatment of OAB. Methods: This prospective cohort study enrolled 80 OAB patients who were then divided into control and treatment groups using a randomized number‐table method. The control group was administered mirabegron alone (50 mg/day), while the treatment group was administered mirabegron orally along with acupuncture at the following points: guanyuan (CV4), zhongji (CV3), and sanyinjiao (SP6). The OAB symptom score (overactive bladder syndrome score [OABSS]), voiding, urgency, nocturia, incontinence, and incidence of related adverse events were compared between the two groups at baseline and after 4, 8, and 12 weeks of treatment.

Nct (2023). "Acute Effect of Osteopathic Visceral Mobilization Techniques." ClinicalTrails.gov.
	The study was planned as a randomized controlled trial. MS patients included in the study will be divided into two groups according to inclusion and exclusion criteria. Diaphragmatic breathing exercises and sacral relaxation, bladder mobilization, which are osteopathic manual therapy techniques, will be applied to the study group. On the other hand, only diaphragmatic breathing exercises will be applied to the control group. Individuals will be treated in a single session. The acute effect of intervention will be examined by making a total of 3 evaluations, pre‐intervention, post‐intervention, and 1 week after the intervention.

Nct (2023). "Adenomyosis and ART." ClinicalTrails.gov.
	Adenomyosis (internal endometriosis) may negatively influence fertility and perinatal outcomes. Inflammation, immune modulation, oxidative stress, extracellular matrix remodelling, aberrant angiogenesis have been implicated in altered oocyte development, uterine receptivity, implantation, successful maintenance of pregnancy. An improvement for infertile women could be a longer GnRH(gonadotropin‐releasing hormone) agonist protocol with the addition of a preventive high‐dose progestin treatment during controlled ovarian hyperstimulation (COH) Infertile women with transvaginal ultrasound (TV‐US) based diagnosis of adenomyosis treated will be randomized into 3 different protocols of COH. Study group 1: Long COH, Study group 2: Long COH + high‐dose dienogest (DNG), Study Group 3: Ultra‐long COH. COH in controls without adenomyosis will be performed using a long GnRH agonist protocol as previous described or using a flexible GnRH antagonist protocol, according to clinical practice. Our aim is to include a total of n=250 women with adenomyosis and n=250 healthy women of a similar age and basal features at the first ART attempt. The primary outcome will be the number of live birth defined as delivery of one or more live‐born infant at > 22 weeks of gestation. Many secondary outcomes will be evaluated as well. Subsequent eventual ongoing pregnancies will be followed as in normal clinical practice, in particular for the risk of preterm delivery, pre‐eclampsia, Caesarean section, fetal malpresentation,small for gestational age, low birth weight and postpartum hemorrhage. In a subgroup of randomized women, the role of endometrial decidualization and its mechanisms will be evaluated in endometrial cells in vitro looking at the response to progesterone and DNG stimulated decidualization markers (in particular osteopontin and prolactin). The different responses will be related to the outcome of ARt and pregnancy related outcomes (preterm delivery, pre‐eclampsia, Caesarean section, fetal malpresentation, small for gestational age, low birth weight and postpartum hemorrhage). Another in vitro study will evaluate the immune system contribution in the implantation period and its changes in the different trimesters of pregnancies after ART conception in women with and without adenomyosis. Blood samples will be obtained ‐ Baseline: prior to ovarian stimulation ‐ Post ovarian stimulation (day of HCG, human chorionic gonadotropin, administration) ‐ Post implantation (2 weeks after embryo transfer, the day of first beta HCG measurement ‐Second (18‐24 gestational weeks) and ‐Third trimester (28‐32 gestational week) of eventual subsequent pregnancies). The aim of this study will be to identify immunological markers such as cellular component and related cytokines in healthy women and women with adenomyosis that undergo ART. In particular the immune system cells population and relative cytokines, the frequency of immune system cells, the interleukins profile, T cells activity and of specific receptors of pregnancy hormone involved in T cell activity will be studied. These results will be linked with estradiol, progesterone and nitric oxide in vivo levels: this will be very important in order to prevent birth losses and to propose new therapies and targets to improve early stages of blastocyst implantation in women with adenomyosis. Forty women with adenomyosis vs. 40 healthy controls will be included in this last part of the study.

Nct (2023). "Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: a Biomarker In Locally Advanced Cervical Cancer." ClinicalTrails.gov.
	A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA‐HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. Patients will be randomized by stratified randomization process to belong to one of the groups: control (Group B) or intervention (Group C), emphasizing homogeneity of risk factors between them. A randomized list will be generated by using a suitable software, using variable size blocks (2 or 4), with stratification for site and staging. The confidentiality of the randomization list will be maintained through an automated, centralized, Internet‐based randomization system, available 24 hours a day (RedCap). Selected patients must receive standard treatment based on concomitant chemoradiotherapy regime, with dose of radiation of 40‐50 greys (Gy) (considering additional boost of 10‐15 Gy in lymph nodes, radiologically or surgically, compromised) and brachytherapy of 30‐40 Gy and cisplatin 40mg/m2 weekly. After four weeks of the end of treatment, a qualitative and quantitative research of cfHPV‐DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV‐DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Nct (2023). "Aerobic vs Core Stability Exercise Training Program in Women With Endometriosis." ClinicalTrails.gov.
	To compare the effects of aerobic and core stability exercise training program on pain, sleep and quality of life in women with endometriosis.

Nct (2023). "Assessing Ketorolac (Toradol) at Oocyte Retrieval." ClinicalTrails.gov.
	Postoperative pain control is an essential component to any surgical procedure. Surgery represents a time during which opioid‐naïve patients may be exposed to narcotics, risking opioid related complications and future opioid‐use disorder. Approximately 150,000 oocyte retrievals are performed per year in the United States, according to the 2017 Assisted Reproductive Technology National Summary Report. A reduction in exposure to narcotics in this field has significant public health implications, particularly given that approximately 6% of new persistent opioid use occurs following minor surgical procedures. Ketorolac (Toradol) has been demonstrated to be a safe and efficacious agent to achieve pain control postoperatively with no significant increase in adverse events. The purpose of this prospective randomized blinded placebo controlled trial is to determine if a nonsteroidal anti‐inflammatory drug (NSAID), Ketorolac (Toradol), can improve pain control and decrease narcotic use after undergoing egg retrieval. Approximately 400 women (n=200 in each arm) will be enrolled according to the inclusion/exclusion criteria among patients of Shady Grove Fertility. Participants will undergo a standard in vitro fertilization cycle (IVF) followed by egg retrieval (ER). Participants will be randomized to receive either IV ketorolac or IV placebo at the conclusion of the egg retrieval, administered by the anesthesia provider. All enrolled patients will receive standard post‐operative pain management. The investigational component of this study lies in assessing post‐operative pain control in the immediate post‐operative period and in the post‐operative period after discharge as reflected by pain scores and narcotic medication usage.

Nct (2023). "Assessing the Safety, Immune Response, and Early Efficacy of a Candida Vaccine in Women With Recurrent Vulvovaginal Candidiasis: a Randomized Controlled Study." ClinicalTrails.gov.
	This is a First Time In Human (FTIH), phase I/II, double‐blind, randomized, placebo‐controlled study to evaluate the safety, immunogenicity and preliminary efficacy of the candidate pentavalent bioconjugate vaccine (Candi5V), administered twice, 2 months apart, with or without adjuvant. The study will be conducted in two subsequent steps: Step 1 (safety cohort): staggered enrolment of small groups of women with history of RVVC, sequentially administered with the half dose of Candi5V non‐adjuvanted and with adjuvant or placebo, followed by groups administered with the target dose of Candi5V non‐adjuvanted and with adjuvant or placebo. Step 2 (target cohort): concurrent enrolment of women with history of RVVC, randomized 1:1:1 to Candi5V, Candi5V + adjuvant and placebo. All study participants will be followed for 12 months after the second vaccination, to assess the vaccine safety profile, the immunological response and the recurrence of any VVC episode.

Nct (2023). "Assessment of Women's Sexual Quality of Life After Benign Adnexal Surgery Using vNOTES Approach." ClinicalTrails.gov.
	This study focuses on women aged 18 to 70 who require surgery for benign adnexal disease (removal of an ovarian cyst, ovary and/or fallopian tube). This is a randomised study, i.e. each woman will be randomly assigned the surgical technique used for the planned operation, either vNOTES or conventional transabdominal laparoscopy. Currently, there are no randomised clinical trials specifically investigating the impact on women's sexual quality of life after benign adnexal surgery compared to conventional transabdominal laparoscopy. Patients appear to be more reticent about the vaginal approach to surgery due to fear of possible alteration of their sexual activity afterwards. Indeed, their fears relate to the vaginal scarring that occurs during the vNOTES surgery. The vaginal scar could cause vaginal pain and pain during sexual intercourse, especially if there is a post‐operative complication with the vaginal scar. The vaginal scar could also alter women's perception of their bodies during sexual intercourse. This study is necessary to answer these questions and increase women's acceptance of the vNOTES technique for benign adnexal surgery. In this way, women would benefit from the advantages of vNOTES without fearing an impact on their sexual quality of life. The primary objective of this study is to demonstrate that the vNOTES technique, although using the vagina as an entry route, does not significantly alter the quality of sexual life of women after benign adnexal surgery compared to conventional transabdominal laparoscopy. The secondary objectives of this study evaluate the effectiveness of vNOTES (impact on pain, length of stay after surgery and patient satisfaction), complications ( during surgery and up to 30 days after surgery), as well as the relationship between the need to cut the surgical specimen for extraction and the difficulty of microscopic analysis. All participants in the study, regardless of the surgical technique assigned to them, will complete questionnaires to assess their quality of sexual life before surgery and at 3 and 6 months after surgery. These are the FSFI (female sexual function), CSI‐16 (couple satisfaction) and a self‐created questionnaire on pain during sex (dyspareunia). These questionnaires will determine whether there is a difference in the women's quality of sexual life before and after surgery, as well as comparing the two surgical techniques. The participants' general and medical data will be collected at the time of study enrolment, during hospitalisation and at one month after surgery to assess the secondary objectives of the study.

Nct (2023). "BAT1308 Combined With Platinum-Based Chemotherapy± Bevacizumab For PDL1-Positive (CPS ≥1) Cervical Cancer." ClinicalTrails.gov.
	The single‐arm Phase II exploratory study designed to evaluate the safety and efficacy of the study drug will include 20‐50 subjects to explore the safety and preliminary efficacy of BAT1308 combined with platinum‐based chemotherapy ± Bevacizumab. Dynamic analysis will be conducted after the inclusion of 20 subject. If the safety of this combination regimen is manageable and the efficacy meets expectations, the enrollment in the Phase II study will be stopped and the Phase III study will be entered. The Phase III study is a randomized, double‐blind, multicenter clinical study of BAT1308 combined with platinum‐based chemotherapy ± Bevacizumab versus placebo plus platinum‐based chemotherapy ± Bevacizumab as first‐line therapy for PD‐L1‐positive (CPS ≥ 1) persistent, recurrent or metastatic cervical cancer. PFS and OS will be used as the combined endpoints, and a superiority design will be adopted with a total sample size of 476 subjects. Stratified block randomization will be performed based on the following random factors: patients will be stratified based on the presence of metastatic diseases at the time of diagnosis (Yes vs. No), PD‐L1 CPS (1‐10 vs. ≥ 10) and planned use of Bevacizumab (Yes vs. No).

Nct (2023). "A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia." ClinicalTrails.gov.
	Up to 60% of endometrial cancer cases are attributed to obesity, in part because obesity promotes development of atypical endometrial hyperplasia (AEH), and up to 40% of women with AEH go on to develop endometrial cancer. The increasing prevalence of obesity in premenopausal women has resulted in increasing rates of AEH in this age group. Hysterectomy with removal of the fallopian tubes and ovaries is 100% effective in preventing endometrial cancer, but this approach results in infertility. Fertility‐sparing treatments exist, such as treatment with oral or intrauterine progestin, but these treatments do not work uniformly and do not combat the underlying cause of endometrial cancer, which is obesity and metabolic syndrome. Additionally, up to 41% of women on progestin eventually experience relapse of AEH or endometrial cancer. Third, many patients have insulin resistance that may worsen with progestin therapy. Thus, to improve treatment of AEH and grade 1 endometrial cancer, prevent and reverse endometrial cancer, and allow women to preserve their fertility, the investigators must integrate an effective weight loss strategy to be given with progestin treatment. It is the hypothesis that premenopausal women with endometrial hyperplasia or grade 1 endometrial cancer who desire uterine preservation will be more likely to have atypia‐free uterine preservation at two years if they receive progestin in combination with a behavioral weight loss intervention versus progestin plus enhanced usual care.

Nct (2023). "Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical Hypothyroidism." ClinicalTrails.gov.
	The goal of this randomized controlled trial is to compare letrozole alone versus letrozole plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical hypothyroidism. The main questions it aims to answer are: Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth rates compared to letrozole alone? Participants will be randomized into two groups: Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a maximum treatment period of 6 months or until pregnancy is achieved. Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.

Nct (2023). "Can Virtual Reality Technology Improve the Patient Experience in Oocyte Retrieval?" ClinicalTrails.gov.
	A non‐pharmacological, non‐blinded, randomized cohort study that will investigate the effect of Virtual Reality technology on the patient experience during oocyte retrieval. The primary objective of the trial is to investigate the impact of Virtual Reality technology on the patient experience

Nct (2023). "Clinical Study of AL2846 Capsules in the Treatment of Advanced Lung Tumor and Advanced Ovarian Cancer." ClinicalTrails.gov.
	This is a multi‐cohort, randomized, open, multicenter Phase II study to evaluate the efficacy and safety of AL2846 capsules in patients with advanced lung cancer and ovarian cancer. Objective response rate (ORR) and progression‐free survival (PFS) are the primary endpoints.

Nct (2023). "Clinical Trial of New Intermittent Single-use Catheter." ClinicalTrails.gov.
	A multi‐centre, open‐labelled, randomised, crossover design. The total study duration for the individual subject will be approximately 4 weeks, consisting of four site visits and two 2‐week test periods at home. Visits 0 and 1 can be performed on the same day. For visit 2 and 3, 2 catheterisations will be performed in a hospital setting (one HCP catheterisation and one self‐catheterisation) for bladder emptying and user experience assessments. Visit 1 and 2 are followed by a home‐use test period, followed by visit 3 which terminates the study.

Nct (2023). "Clinical Trial of New Single-use Compact Intermittent Catheter." ClinicalTrails.gov.
	The study is a randomised, single‐blinded, controlled crossover study. The total study duration for the individual subject will be between two days ‐ two weeks, consisting of three site visits. Visits 0 and 1 can be performed on the same day. Visit 2 can be performed the day after visit 1. For visit 1 and 2, catheterizations will be performed in a hospital setting by a health care professional for bladder emptying assessment and collection of urine samples for haematuria assessment. A sub‐group of subjects (all enrolled subjects at DK sites) will be asked to conduct a self‐catheterization at visit 2 after hcp catheterization and evaluate discomfort and PVR. The total study duration for the individual subject will be up to 14 days.

Nct (2023). "Clinical Trials Evaluating the Effect of Metformin Treatment on Function Endometrium in Women Diagnosed With Idiopathic Infertility." ClinicalTrails.gov.
	Randomized, controlled, double‐blind, three‐arm clinical trial in which 75 women will be randomized to treatment with metformin, 75 women to treatment with placebo and 50 women to the observation group. The medical intervention will last 24 weeks (6 months). Women with confirmed idiopathic infertility, in whom infertility factors have been excluded during full diagnostics, will be included in the study

Nct (2023). "Combined Chromium With Letrozole Versus Letrozole Only in Induction of Ovulation in Patients With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	Randomized controlled trial

Nct (2023). "Combining Pelvic Floor Rehabilitation With Postural Re-education in Women With Stress Urinary Incontinence and Chronic Low Back Pain: a Preliminary Study." ClinicalTrails.gov.
	Stress Urinary incontinence (SUI) is a common health condition in female population. Although its prevalence increases with the age, women of all ages could be affected. Several epidemiological studies have shown an association of SUI with Low Back Pain (LBP) demonstrating, moreover, that the presence of one condition may predispose the patient to the onset of the other. Concerning the LBP, the clinical practice guidelines provided recommendations for physical rehabilitative treatment. Different techniques and physical exercises have been developed and it is difficult at the date to affirm the superiority of one approach as compared to another. Moreover, the crucial role plays by the pelvic floor muscles (PFM) both as an integral part of trunk and lumbo‐pelvic stability and in maintenance of urinary continence, lead the pelvic floor muscles disfunction to be associated both with SUI and LBP, making the PFM rehabilitation a useful approach in both the conditions. In this rehabilitative context the present study aims to verify the effectiveness of a global physical approach based on postural re‐education combined to the pelvic floor rehabilitation in women with diagnosis of stress urinary incontinence associated with non‐specific chronic low back pain.

Nct (2023). "Comparison of Dequalinium Chloride (Fluomizin) vs Oral Metronidazole for the Treatment of Bacterial Vaginosis." ClinicalTrails.gov.
	Eligible patients who signed informed consent were randomized to receive treatment with either dequalinium chloride (+ oral placebo) or metronidazole (+ vaginal placebo) for up to 7 days. Primary objective was clinical cure rate at one week after start of treatment. Control visits to assess outcomes were done after end of treatment and after one month.

Nct (2023). "Comparison of Different Massages Tecniques on Chronic Pelvic Pain." ClinicalTrails.gov.
	The aim of this study is to investigate and compare the effectiveness of transverse friction and Thiele massage on pain, quality of life and sexual functions in female patients with chronic pelvic pain. The study will be performed on 20 female patients with pelvic floor muscle tenderness, who applied to the Urology Clinic in Istanbul and were diagnosed with chronic pelvic pain.

Nct (2023). "A Comparison of Hyaluronic Acid and Estradiol Treatment in Vulvovaginal Atrophy." ClinicalTrails.gov.
	This randomized, controlled, monocentric, prospective, comparative (before/after) study was conducted at Koru Ankara Hospital between April 2023 and September 2023. Patients were randomized into 2 groups. A total of 300 patients, 150 in each group, were included in the study. Informed written consent was obtained from the volunteers who willingly participated in the study. Group I received 25 µg vaginal estrodiol (Vagifem®). 1 tablet a day for two weeks, then 2 times a week for the next 2 weeks. Group II received 5 mg of vaginal hyaluronic acid every day for 14 days, then 2 days a week for the next 2 weeks. Hyaluronic acid gel for vaginal use was supplied by ORTHOGEN®. The treatment period lasted 1 month in both groups. Before receiving treatment, patients who consented to participate in the study were examined by a Gynecologist, and Vaginal Health Index (VHI)12 score was determined. After the end of the treatment period, the patients were re‐evaluated by the same physician, and the VHI score was obtained again. The VHI is the most common score based on vaginal elasticity, secretions, pH, presence of petechiae on the epithelial mucosa, and hydration assessment. The score can range from 5 to 25, and <15 is considered an atrophic vagina index. Vaginal pH was measured by placing pH paper on the anterior wall of the vagina. A value >5 pH was defined as decreased estrogen activity13. The effect on the primary outcome VHI index was investigated.

Nct (2023). "Comparison of the Effects of External Electrical Stimulation Protocols in Women With Overactive Bladder." ClinicalTrails.gov.
	OAB is a condition defined by the International Continence Society as the presence of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology. External electrical stimulation has positive effects on OAB. However, there are not enough studies on how often this stimulation is applied. Studies are needed on this subject.

Nct (2023). "Comparison of the Effects of Transcutaneous Electrical Nerve Stimulation Protocols in Women With Overactive Bladder." ClinicalTrails.gov.
	OAB is a condition defined by the International Continence Society as the presence of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology. TENS has positive effects on OAB. However, there are not enough studies on how often this stimulation is applied. Studies are needed on this subject.

Nct (2023). "Comparison of the Transcutaneous Tibial Nerve Stimulation and Drug Treatment' Effects in Women With Overactive Bladder." ClinicalTrails.gov.
	According to the inclusion and exclusion criteria, 34 female patients with OAB were enrolled in the study. The patients were randomly divided into two groups, with 17 individuals in each group. Patients with odd case numbers were assigned to the Oral Solifenacin group, while those with even case numbers were assigned to the TTNS group. Prior to treatment, the sociodemographic characteristics, birth history, and past treatment information of all participants were recorded. Basic urogynecological evaluation, pelvic floor ultrasound, and urine culture were performed. To assess symptoms and quality of life, the Overactive Bladder Assessment Form (OAB‐V8), Incontinence Quality of Life Scale (I‐QQL), Incontinence Impact Questionnaire (IIQ‐7), Urogenital Distress Inventory (UDI‐6), and a three‐day bladder diary were used. After 6 weeks of treatment, all evaluations were repeated. The treatment regimen consisted of once‐daily oral solifenacin for the medication group and 2 sessions per week, 30 minutes per session, for 12 sessions using the Urostim‐2 device for the TTNS group. The stimulation intensity was increased until a motor or sensory response was obtained, and the threshold value was determined. The entire TTNS procedure was performed under the supervision of an expert physician at the Urogynecology Outpatient Clinic of Ege University Hospital. Statistical analysis was conducted using SPSS 20.0.

Nct (2023). "Comparison of Virtual Pelvic Floor Physical Therapy With a Pelvic Floor Trainer in the Treatment of Stress Urinary Incontinence." ClinicalTrails.gov.
	This will be a prospective cohort study of women > 18 years of age with symptoms of stress urinary incontinence, recruited via an online recruitment tool. After screening, patients meeting inclusion criteria will be given instructions on how to indicate desire to participate in the study. The patient will then be contacted for study participation, including explanation of study and details and completion of Informed Consent. Participants will then complete a pre‐treatment urinary incontinence symptom questionnaire(ICIQ). After completion of the above, the participants will then be randomized to one of three arms: 1. Pelex Upp (study device) only 2. Pelvic floor physical therapy + Pelex Upp(device under study) 3. Pelvic floor physical therapy only For those given a Pelex Upp, they will also receive educational materials on use of the device, and a treatment schedule. For those participants given a Pelex Upp, a standardized biofeedback‐mediated pelvic floor muscle training program with the study device 10 minutes a day, four times a week for 4 weeks, will be performed. For those subjects undergoing pelvic floor physical therapy only, they will perform Kegel exercises on a similar schedule. There will be a mid‐study check in to assure all devices are functioning appropriately. At the end of the study, participants will complete a post‐treatment urinary incontinence symptom questionnaire(ICIQ). Endpoint of the study will be change in stress urinary incontinence symptoms as measured by the ICIQ. The ICIQ will be collected at 2 time points: before study entry, and at study close.

Nct (2023). "Comparisons of the Impact of Monotherapy With Mirabegron or Tolterodine Versus Combined Treatment With Mirabegron and Tolterodine on Autonomic Function and Bladder Blow Flow in Women With Overactive Bladder Syndrome: a Randomized Controlled Study." ClinicalTrails.gov.
	Patients and methods: We will conduct a prospective randomized controlled study in the outpatient clinic of Department of Obstetrics and Gynecology of Far Eastern Memorial Hospital, and will recruit 150 female patients with overactive bladder syndrome. All female patients with overactive bladder syndrome enrolled in the study will be requested to fill in the urgency severity score, the overactive bladder symptom score questionnaire, and the King's health questionnaire before taking the drug and four weeks and twelve weeks after taking the drug. In addition, measurement of heart rate variability and bladder blood perfusion will be performed. Expected results: We will obtain the impact of monotherapy with tolterodine or mirabegron versus combined therapy on heart rate variability and bladder blood perfusion in women with overactive bladder syndrome.

Nct (2023). "Comparisons of the Therapeutic Effects of Dienogest and Danazol on Endometriosis." ClinicalTrails.gov.
	Objective: Women with adenomyosis or endometripsis are often suffered from dysmenorrhea or menorrhagia. Dienogest and danazol are frequently used for the treatment of endometriosis. However, there was no literature mentioned about which medication is better for the treatment of endometriosis. Thus, the aim of this study is to evaluate the efficacy between dienogest and danazol. Methods: All consecutive women, who have endometriosis, will be randomized to receive dienogest or danazol treatment, and will assess symptoms severity, receive CA125 examination, sonographic examination at baseline, 4 weeks and 16 weeks after treatment.

Nct (2023). "Coughing at Time of Cervical Biopsy." ClinicalTrails.gov.
	Colposcopy is a frequently practiced examination and Colposcopy guided biopsy causes pain. A few trials Investigated whether medical interventions such as the application of lidocaine led to reduced pain perception with inconsistent results. Only one trial compared coughing versus no coughing at the moment of biopsy. Although the results of this study did not lead to a significant difference between the two study arms, coughing seems to positively affect pain perception. Since the patients are, in the best case, their own controls when it comes to subjective parameters such as pain perception, we prefer a cross‐over rather than a parallel group design. Based on the descriptive variables for pain during biopsy with and without cough determined in the pilot study, a case estimate for a prospective randomized cross‐over study will be carried out. Since two biopsies are usually taken from the cervix in daily practice, the now planned pilot study in a cross‐over design envisages the following two study arms: 1. Group I: Patients cough during the first biopsy, they do not cough during the second biopsy 2. Group II: Patients cough during the second biopsy, they do not cough during the first biopsy The primary Outcome measure is the difference in the patients' perception of pain during the first and second biopsy on the cervix (ectocervix), measured using an 11‐part numerical analogue scale (11‐item NAS).

Nct (2023). "The CRESCENDO Program (inCRease Physical Exercise and Sport to Combat ENDOmetriosis)." ClinicalTrails.gov.
	a. Objectives and research hypothesis 1. Endometriosis and its consequences Endometriosis is a chronic disease characterized by growth of endometrial tissue outside the uterine cavity which affects 200 million women (The investigators use the word "women" generically. However, this study takes into account gender identity. In other words, a person with endometriosis may identify as a man, as woman or no/other gender.) worldwide. In addition to infertility, one of the most common symptoms of endometriosis is pelvic chronic pain. Evidence has suggested that these symptoms result from a local inflammatory peritoneal reaction caused by ectopic endometrial implants that undergo cyclic bleeding. This disease generates significant health care costs (e.g., 9,5 billion in France) because there is no definite cure for it and its management involves pain related treatment and/or surgery. Research showed that these treatments are only relatively effective in reducing pain. This pain can cause psychological distress and interpersonal difficulties that are as difficult to live with as the pain itself. Compared to women who do not suffer from endometriosis, women with this disease develop a lower sense of femininity, altered body image, higher levels of stress, depression and anxiety. These factors affect their quality of life (QoL) and can have deleterious effects on the response to treatment. Interpersonal relationships are also impacted such as romantic, professional and social relationships, because the symptoms make it difficult to move and carry out daily activities. However, studies on the psychological and social consequences of endometriosis are scarce, few have investigated life‐partners' view of the disease and its consequences, and all adopt cross‐sectional designs. 2. The effects of physical activity on endometriosis: a question for further investigation In their recent publication, INSERM (L'Institut national de la santé et de la recherche médicale) highlights the beneficial effects of regular physical activity (PA) and adapted physical activity (APA) on chronic diseases. Research suggested that (A)PA may have a beneficial effect on the physical symptoms and the psychological and social consequences of these diseases, thus may be also in endometriosis context. However, studies questioning the link between PA and endometriosis (and its symptoms) are rare, cross‐sectional, and their results are inconsistent. The scarcity of studies can be explained by the fact that due to the painful symptoms caused by the disease; women do not practice much PA spontaneously and autonomously or even avoid practicing. In addition to this difficulty, widely recognized barriers to PA (i.e., lack of time, lack of adequate and nearby infrastructure, and low self‐confidence and motivation for PA) can also contribute to the low level of PA. It is worth noticing that, in the specific context of endometriosis, the barriers and facilitators to the practice of PA are not clearly identified. Otherwise, due to their cross‐sectional design, it was not possible for these studies to establish a causal link between PA and endometriosis. A randomized controlled trial (RCT) is needed to test the effects of (A)PA on the symptoms of endometriosis and its consequences. 3. Summary of scientific barriers to be lifted Based on previous research and their limits, there are three major scientific barriers to be lifted regarding the investigation of the link between (A)PA and endometriosis: 1. There is a need to better understand the psychological and social factors associated to endometriosis. For instance, consequences of endometriosis on these factors and the impact of the disease in romantic relationships (i.e., on the patient and on her life partner2) need to be more documented. Some of these factors could be related to patient PA or could mediate or moderate the relation between endometriosis (and its symptoms) and PA. 2. Although barriers of PA are well known, in the context of endometriosis the barriers and facilitators to the practice of PA re not clearly identified. Given the specificity of this disease which only affect women and its impact on body functioning and body perception, this topic deserves to be investigated. 3. Otherwise, due to their scarcity and their cross‐sectional design, it was not possible for previous studies to strongly establish a causal link between PA and, endometriosis and its symptoms. Conducting a RCT may help to overcome this limitation. 4. Objectives and hypotheses The investigators' ambition for this original work is to fill these gaps in the existing literature and to allow a more comprehensive view of the phenomena at play in the relation between PA and endometriosis. For this purpose, The investigators will use a multimethodological design and a multidisciplinary approach in one of the first intervention study led with patients who suffer from endometriosis. Within two work packages (WP) the investigators will identify the perceived effects of the disease specifically those related to PA, and investigate the reasons why patients are or are not physically active using qualitative and quantitative methodologies (WP1). Otherwise, this first study will allow investigating and thus identifying the barriers and leverages to PA in the specific context of endometriosis. This information could be particularly interesting in the development of the WP2. Indeed, in WP2 which is an exploratory study, The investigators will investigate the effects of an APA program delivered by videoconferencing which include therapeutic patient education (TPE) on PA and sedentary behaviors (SED), on perceived pain, QoL, and on patients' physical, physiological (inflammatory status and oxidative stress) social and psychological health. The primary objectives of the WP2 were to investigate the effects of the CRESCENDO program on PA and SED but also on perceived pain and QoL. The investigators choose to also investigate pain and QoL as primary outcomes because their evolution are key elements in endometriosis setting. Thus, the primary outcomes were defined as the proportion of patients who 1. achieve the internationally recommended level of PA international recommendations, i.e., at least 150 minutes per week of moderate to vigorous PA 2. indicate a decrease in their perceived pain level (at least 1 point or 1 centimeter on visual analogue scale) 3. indicate an increase in their QoL level (at least 20 points) The investigators hypothesize that the CRESCENDO program could (H1) complement current treatments for endometriosis by increasing PA and reducing SED, reducing pain (due to the decrease of inflammatory status), increasing QoL, (H2) have beneficial effects on patients' physical, psychological and social health as well as physiological factors. Finally, a program combining APA and TPE will be more effective than one that offers these interventions separately (H3). It is worth noticing that, the questionnaire which will be propose in WP2 will be similar to those proposed in WP1. The investigators expect to find coherent results, that is, The investigators expect to explain part of the WP2 results based on WP1 results. In view of the expected benefits for the patients benefiting from the program, the investigators hope that the results of this study will lead to the generalization of the integration of APA and TPE programs into endometriosis care protocols. These practices could be considered as a complement, or even an alternative, to treatments to reduce healthcare costs. The use of videoconferencing to deliver APA programs would remove barriers to PA related to the availability and proximity of sports facilities and scheduling constraints, as much as allow the continuity of the practice even if the health context imposes a lockdown (e.g., COVID‐19), while allowing for a group practice that is adapted and emotionally reassuring. Finally, the inclusion of chronic diseases among the diseases for which patient can benefit of a medical prescription for sport (i.e., APA) and the launch of the national strategy against endometriosis lead by C. Zacharop lou in Marsh 2021, confirmed in January 2022, emphasized the importance of these related topics: endometriosis and APA. The investigators hope the results of this study to be informative to select the type of care which is the most adapted and efficient to endometriosis patients, that is to shed light on the importance of proposing a comprehensive care which could have an impact on physical and psychosocial variables.

Nct (2023). "Cryocompression to Reduce Chemotherapy-induced Peripheral Neuropathy in Gynecologic Cancer - COHORT 2." ClinicalTrails.gov.
	Participants will be randomized by patient to receive cryotherapy wraps plus compression therapy (cryocompression) versus cryotherapy wraps alone applied to the bilateral hands and feet. Participants will receive cryotherapy (+/‐ compression) for the duration of their taxane infusions. Participants will be asked to complete the FACT‐NTX survey and a PNQ neuropathy surveys at each infusion visit to evaluate symptoms related to neuropathy. Participants will also complete a brief acceptability and tolerability survey at each visit. Lastly, a staff satisfaction survey will be administered at each visit as well. The investigators will test the hypothesis that the average final visit FACT‐NTX11 scores in the cryotherapy group are noninferior to the cryocompression group with a noninferiority margin of 2.5 points. The investigators will routinely monitor for the following adverse events: frost bite, (unexpected) hospitalizations, and death.

Nct (2023). "Curio Digital Therapy for the Treatment of Post-partum Depression." ClinicalTrails.gov.
	Women between 18 and 50 years of age who have had a live birth within 3 months prior to study start date and have a diagnosis of mild to moderate PPD. A total of 200 women will be recruited to volunteer in the study with 166 assigned to the intervention arm and 37 assigned to the control group.

Nct (2023). "Dark Chocolate, Coconut Water, and Ibuprofen in Managing Primary Dysmenorrhea." ClinicalTrails.gov.
	Dysmenorrhea, commonly known as period pain, is a prevalent condition that affects a large number of women during menstruation, causing discomfort and often leading to reduced productivity. While several treatments are available to alleviate the pain, there is limited information on the comparative effectiveness of different interventions, including green coconut water, dark chocolate, and Ibuprofen. This research aimed to conduct a randomized controlled trial to compare the effectiveness of green coconut water, dark chocolate bars, and Ibuprofen in managing primary dysmenorrhea. A total of 45 participants were enrolled in the study and randomly assigned to one of three intervention groups: green coconut water, dark chocolate bars, or Ibuprofen. The green coconut water group received 330 ml of pure green coconut water, which is known for its potential health benefits and natural electrolyte content. The dark chocolate group received 35 grams of 70% dark chocolate, as some studies have suggested its potential role in pain relief due to the presence of bioactive compounds. The Ibuprofen group received 400 mg of the common over‐the‐counter nonsteroidal anti‐inflammatory drug (NSAID) known for its analgesic properties. To assess the effectiveness of each intervention, pain intensity was measured before and after treatment using validated pain scales. The Kruskal‐Wallis test, a non‐parametric statistical method, was used to analyze the data and compare the effectiveness of the three interventions.

Nct (2023). "DETERMINE Trial Treatment Arm 02: atezolizumab in Adult, Teenage/Young Adults and Paediatric Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition." ClinicalTrails.gov.
	DETERMINE Treatment Arm 02 (atezolizumab) aims to evaluate the efficacy of atezolizumab in adult, paediatric and teenage/young adult (TYA) patients with rare* cancers with high TMB or high MSI or proven CMMRD disposition and in common cancers where high TMB/MSI or proven CMMRD is considered to be infrequent. *Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub‐cohorts may be defined and further expanded where promising activity is identified to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers. OUTLINE: Pre‐screening: The Molecular Tumour Board makes a treatment recommendation for the participant based on molecularly‐defined cohorts. Screening: Consenting participants undergo biopsy and collection of blood samples for research purposes. Treatment: Participants will receive atezolizumab until disease progression, unacceptable toxicity or withdrawal of consent. Participants will also undergo collection of blood samples at various intervals while receiving treatment and at EoT. After completion of study treatment, patients are followed up every 3 months for 2 years. THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.

Nct (2023). "Determining the Effect of Telephone Counseling Service Provided to Primiparous Mothers on Postpartum Depression." ClinicalTrails.gov.
	The aim of this study is to determine the effect of telephone counseling services provided to primiparous mothers on postpartum depression. Hypotheses H01; there is no difference between the postpartum depression score of the telephone counseling services group and the postpartum depression score of the control group. The study will be carried out in two different groups. The practice will start with meeting the women who give birth will be visited by the researcher at the postpartum clinic at least 6 hours after normal birth and 12 hours after cesarean births. After the women are evaluated in terms of eligibility criteria for the research, the women who are eligible will be informed about the research and written informed consent will be obtained from the women who accept. The random distribution of women to the study groups will be carried out using the Block Randomization method. The following applications will be made to the groups. The researcher will contact the experimental group by phone. He will introduce herself and 6 weeks (during postpartum). It will provide the mother with the consultancy service she needs about herself and the newborn 24 hours a day. After 6 weeks, the training will end and the third researcher will make post‐tests of the depression scale to both groups without knowing the experimental and control groups.

Nct (2023). "Diet, Cardiometabolic Risk (CM) and Menopause Symptoms." ClinicalTrails.gov.
	Group 1 will first follow the MedDiet pattern for six weeks and then follow the UCLP diet pattern for six weeks. Group 2 will also follow both diet patterns but in the opposite order. Week 0 will be the baseline, week 6 will be the interim point and week 12 will be the endpoint. Data collection Some data will be collected at the University of Chester laboratories, including anthropometric measurements, blood pressure and blood samples. A small fasted blood sample will be collected via finger prick (Alere Cholestech LDX® Analyzer (Alere San Diego Inc. USA)). Participants will also be talked through the guidance notes for the diets at this point. Other data, food diaries and a questionnaire asking about recent physical activity and menopause symptoms will be completed online. Demographics At baseline participants will be asked to complete a brief questionnaire to answer a few demographic questions, including date of birth, ethnicity, income category, level of education, whether (and if so which) using any form of hormone replacement therapy (HRT) or contraception. Participants will be asked at interim and endpoint whether there have been any recent changes with regards to HRT and contraception methods. Dietary intake Participants will be asked to complete a total of seven four‐day food diaries. The first diary will be completed in the week before participants attend their first appointment in the laboratory. This diary will give a snapshot of the participants' habitual diet prior to joining the intervention. The other four‐day food diaries will be completed in weeks 2, 4, 6, 8, 10 and 12. Physical activity Data on physical activity over the previous four‐week period will be collected at baseline, interim point and endpoint. Participants will be asked to complete the Recent Physical Activity Questionnaire (RPAQ). Data analysis Blood sample Blood samples will be used to assess whether participants have ‐ elevated total cholesterol levels (>5 mmol/L) ‐ elevated LDL cholesterol levels (>3.0 mmol/L) ‐ elevated non‐HDL cholesterol levels (>4 mmol/L) ‐ decreased HDL cholesterol levels (<1.3 mmol/L) ‐ elevated triglyceride levels (>1.7 mmol/L) ‐ elevated glucose levels (> 5.6 mmol/L) HDL‐C, glucose and triglyceride levels will also be used together with waist circumference and blood pressure data to assess whether participants present with metabolic syndrome at baseline, interim point and endpoint according to the definition of Alberti et al. (2009) Dietary intake Food diary data will be analysed using the dietary assessment software Nutritics (2021). The data from the analysis will also be used to identify the intake of phytoestrogen‐rich foods (associated with milder menopause symptoms) and the average intake of phytoestrogens. Dietary adherence and diet quality Following on from the analysis of the food diaries adherence to the MedDiet will be assessed by applying the Mediterranean Diet Score. Adherence to the UCLP Menopause will be assessed by applying an amended version of the Portfolio Diet Score. The scoring system will be slightly adjusted where there are differences in terms of amounts to be consumed of the four portfolio foods. Physical activity Each activity across the four domains of the RPAQ has a MET score assigned based on Ainsworth et al.'s (2011) updated Compendium of Physical Activities to categorise the activity as sedentary, light, moderate or vigorous intensity. Recoding of the completed RPAQ will follow the script devised by Medical Research Council (MRC) Epidemiology Unit (Scott et al., 2013; available to download at www.mrc‐epid.cam.ac.uk/physical‐activity‐downloads/). Statistical analysis Descriptive statistics (means (M) and standard deviation (SD)) will be produced for all data collected. Data will also be analysed for correlations between dietary intake, diet quality and changes to cardiometabolic risk (CMR) and to menopause symptoms. Mixed ANOVAs and linear and logistic regression analysis will also be employed. If necessary data will be adjusted for factors, such s physical activity, ethnicity, HRT intake, contraceptive intake, educational level and income category.

Nct (2023). "Do Intravaginal Devices Reduce Urinary Incontinence in Female Runners?" ClinicalTrails.gov.
	Urinary incontinence (UI) is a serious public health concern, imposing a significant financial burden. In Canada the direct and indirect health costs associated with UI total over 3.6 billion annually and no estimates of disease burden take into account deconditioning that results from withdrawal from physical activity nor effects on mental health or quality of life. Although the primary risk factor for UI is pregnancy and vaginal delivery, it was recently reported that between 20% and 40% of nulliparous females report urine leakage when they engage in physical activity. Urinary continence is maintained as long as urethral closure pressure remains higher than bladder pressure. This is accomplished through a complex combination of mechanisms, including smooth and striated urethral sphincter muscle action, urethral venous engorgement and mucous secretions within the urethra, and the proper transfer of loads to the urethra, which depends on adequate bladder neck and urethral connective tissue support as well as pelvic floor muscle (PFM) action. The associations among physical activity, pelvic floor morphology and function, and UI are not clear. A recent systematic review retrieved 18 mainly small studies investigating the association between physical activity and pelvic floor dysfunction. Exercise at mild to moderate intensity appears to be protective, decreasing both the odds and the risk of experiencing urinary incontinence. However, females who engage in high‐impact activities such as running are more likely to report UI during exercise than those who engage in mild or moderate intensity exercise, thus chronic and repetitive loading of the pelvic floor may have negative consequences. While there is Grade A evidence for pelvic floor muscle training and some evidence for intravaginal pessaries to reduce symptoms of UI in general female populations, no study has investigated about interventions specific to running‐induced UI.

Nct (2023). "The Effect of a Mindset Management Approach on Stress Levels in Women With Infertility." ClinicalTrails.gov.
	The study follows a randomized controlled, unblinded, between‐groups, and repeated measure design. The study period will last 16 weeks for both groups. Potential subjects will first be screened by a patient service representative at the SGF office in Roanoke, who will generate a report of new patients who were seen recently. The patient service representative will then reach out to those patients via email and introduce them to the study. If they are interested in enrolling, they will fill out the REDCap survey linked in the email, which asks for their name, email, and phone #. If they fill out the survey, a designated study team member will call them and verify the patient by name. Designated study team members include clinical research personnel at SGF, co‐investigators at Virginia Tech, the Principal Investigator, and medical students at Virginia Tech. The designated study team member will introduce the patient to the study. If they are interested in enrolling, they will confirm their eligibility, and review the consent form with the patient. Participants will sign the eConsent using a finger or mouse to sign. The participants will sign the consent form while having a conversation over the phone with a designated study team member. The designated study team member will verify that the participant's signature has been saved correctly in REDCap. If participants don't answer their phone, the designated study team member may email them to set up a time to discuss the study. Participants will be randomized to one of two groups: the OC research‐related intervention group or the control group. Participants will then be sent instructions on next steps, based on their randomization result. Throughout the study period, subjects will complete surveys through REDCap. These will be emailed to them. Surveys will include a demographics questionnaire, the COMPI‐FPSS, the Client Satisfaction Questionnaire for Internet Interventions CSQ‐I, and additional questions. Demographic questionnaire components were developed based on previous research (Clifton et. al 2020, Kirca et. al 2019) and include questions on age, gender, relationship status, length of current relationship, number of pregnancies, number of living children, ethnicity, race, income, employment status, highest level of education, type of area patient resides in, mental conditions, and current use of therapeutic interventions. The COMPI‐FPSS is a measure of fertility‐related stress (Sobral et. al 2016). It is based on the Fertility Problem Inventory (FPI) (Abbey et. al 1991) and an interview study completed in couples, which analyzed the psychosocial consequences of infertility (Schmidt et. al 2006). The scale is a reliable and validated measure of stress, specifically related to infertility, that can be applied in various cultures and countries (Sobral et. al 2016). Compared to two other known infertility‐specific psychometric measures (FPI and Fertility Quality of Life), the COMPI‐FPSS has a practical advantage due to its shorter length, and it differentiates most effectively between its domains (Pedro et. al 2016), which include a personal, marriage, and social domain. With the permission of Dr. Schmidt, the creator of the COMPI‐FPSS, the marriage domain is labeled a "relationship" domain in order to encompass all types of relationships. If the patient is not in a relationship, then the relationship domain questions will be omitted. The COMPI‐FPSS includes questions about infertility‐related stress, specifically, rather than general stress. This makes it a reliable tool because it controls for stress from other aspects of life. It employs a Likert scale, which includes a variety of statements that participants may choose from when responding to qualitative questions. Participant scores will be added and analyzed within each domain and overall. A higher score means higher stress levels, while a lower score means lower stress levels. The CSQ‐I is a reliable measure for Web‐based interventions (Boß et. al 2016) and has been used in previou tudies to evaluate satisfaction with mental health interventions (Bäuerle et. al 2021). Like the COMPI‐FPSS, it utilizes a Likert scale. Participant scores will be added and analyzed for each question and overall. A higher score means higher satisfaction, while a lower score means less satisfaction. The purpose of the survey completed immediately after enrollment is to collect demographic information and obtain baseline COMPI‐FPSS scores. The surveys completed at the ten‐week study time point (after the experimental group has completed the research‐related intervention) will be used to evaluate any changes in COMPI‐FPSS scores, to assess if other stress‐reducing interventions outside of the study are being utilized by subjects, to assess adherence to the research‐related intervention protocol, and to determine satisfaction with the research‐related intervention and fertility treatment. The final survey, completed at the 16‐week study time point, will be used to evaluate whether the OC method has a prolonged effect on stress levels (i.e., whether COMPI‐FPSS scores are similar to scores at week 10), to assess if other stress‐reducing interventions outside of the study are being utilized by subjects, to assess continued interaction with the study materials after completion of the ten‐week research‐related intervention, and to explore continued satisfaction with the research‐related intervention and fertility treatment (i.e., whether the perception of the research‐related intervention remains the same). Following completion of the first survey, participants randomized to the control group will receive standard fertility care, which does not currently include any stress‐decreasing interventions or information. The control group will have access to the OC materials after the study period. Participants in the intervention group will begin the OC research‐related intervention that will last ten weeks. Participants' fertility journey will not be delayed while they complete the intervention. Rather, it will happen simultaneously. The study team will be collaborating with OC who designed a ten‐week curriculum that includes all the materials their clients already engage with. The curriculum will involve assignments that will take approximately three hours per week to complete, weekly one‐hour group coaching sessions with a certified coach, monthly one‐hour live group master classes, and monthly 30‐minute welcome new members group sessions. Participants will also have the option to join the Organic Conceptions Facebook group. The group sessions will be attended by both subjects and OC clients. Before every group call, participants will be sent a reminder message with instructions on how to remain anonymous during the sessions, if they wish to do so. To verify that participants are completing modules, the OC portal has the ability to track their completion. In addition, subjects will be asked the extent to which they are interacting with the assignments, how many new member welcome sessions they attended, how many live group coaching sessions they attended, how many live master classes they attended, and whether they joined the Facebook group as part of their surveys. However, they will not be asked to turn in their workbook due to their private nature. To evaluate whether providing the OC research‐related intervention increases the subject's likelihood of attending their initial appointment, completing the fertility testing and treatment process, patient retention, conversion, and completion rates will be measured. Subjects will be considered "retained" if they attend their initial appointment and return for their follow‐up appointment within six months of their initial consultation. If they do not return or return later than 6 months, they will be considered "unretained." Similarly, subjects will be considered "converted" if they enter a fertility treatment cycle within six months of their follow‐up visit. If they do not, they will be considered "unconverted." Subjects will be consi e ed "complete" if they complete their fertility treatment cycle. If they do not, they will be considered "incomplete." In addition, study participants will be asked whether they conceived (experienced a positive pregnancy test, confirmed by blood work) as part of the surveys completed at the ten‐week and 16‐week time points in the study. The electronic medical record system will be used to verify this information. If they do not conceive during the study period, their charts will continue to be monitored in the medical record system for one year.

Nct (2023). "Effect of a Probiotic on the Female Genital Tract Microbiota of Participants With Fertility Disorders." ClinicalTrails.gov.
	In the last decades, numerous publications have broken the old paradigm that considered the urogenital tracts as sterile, demonstrating that microorganisms present in the urogenital tract represent the 9% of the whole human microbiome. Healthy urogenital microbiome improves implantation rate and pregnancy outcomes, whereas 40% of dysbiosis prevalence is observed in women under assisted reproductive treatment (ART). Infertility causes are associated with male, female, or combined failure. It has been shown that oral probiotic treatment, mainly with Lactobacillus, recovers a healthy vaginal microbiota without safety concerns. An interventional, randomized, double‐blind, placebo‐controlled study will be conducted to confirm the positive effect of the commercial probiotic product Fertibiome® on the vaginal dysbiosis of couples or women with fertility disorders. The duration of the study will be of 6 months approximately, including 6 months of product intake. In case of pregnancy during intervention, women will continue their participation until week 12 of gestation. Participants will be randomly assigned to one of the two study groups: control group with placebo administration or probiotic administration group. Women will take 1 capsule every 12 hours and men 1 per day. In case of women participating alone they will take 1 capsule every 12 hours. In case of pregnancy, only women will continue taking 1 capsule per day for the first 12 weeks.

Nct (2023). "Effect of Acupressure on Postoperative Pain With Gynecologıcal Surgery." ClinicalTrails.gov.
	In this study, the effect of acupressure on postoperative pain level in women with abdominal gynecologıcal surgery will be studied and it will be conducted as a randomized controlled intervention study to examine the relationships with each other.The sample group will consist of 102 women, 51 in the intervention group and 51 in the control group.Within the scope of the study, the data will be collected using the 'Personal Information Form and Short‐Form McGill Pain Questionnaire(SF‐MPQ)' created by the researcher. Data will be obtained by the researcher by faceto‐face interviews with women. In addition, women in the intervention group will receive acupressure once on postoperative days 0 and 1. Acupressure points related to gynecological surgery (large intestine (LI4), stomach (ST36) and spleen (SP6)) will be applied for a total of 12 minutes with 2 minutes of pressure on each point. Women in the control group will continue their routine care. Data will be evaluated with SPSS‐26 package.

Nct (2023). "The Effect of Baby Massage on Postpartum Depression and Maternal Attachment." ClinicalTrails.gov.
	The transition to motherhood is one of the life stages that brings about stress and change. Primiparous mothers, who will experience motherhood for the first time due to anxiety about the unknown, may experience more stress and their communication with their babies may deteriorate. In this process, the mother's seeing, touching and interacting with her baby positively affects her perception of her baby. The easiest and most natural way to do this is baby massage. Touching and massaging the baby maintains the baby's body contact, which strengthens the baby's sense of trust and supports the mother's development of attachment behavior. It also reduces mothers' levels of stress hormones such as cortisol and relieves depressive symptoms.

Nct (2023). "The Effect of Baby Massage Training Given to Pregnant Women on Maternal Attachment and Postpartum Depression." ClinicalTrails.gov.
	The research to be conducted within the scope of the project will be randomized controlled, and the population of the research will be primiparous pregnant women reached through social media. Primiparous pregnant women in the 32nd ‐ 40th weeks of pregnancy will be included in the study, and the sample size is determined by using the G*Power (3.1.9.2) program, considering a margin of error of 0.05 and data loss, with a power of 95% and a medium effect size; 27 people should be included in the experimental (baby massage) group and 27 people in the control group. In determining the groups, participants will be assigned to experimental and control groups using the "Randomizer.org" program. Pregnant women included in the research will be informed about the study and will be presented with an "Informed Consent Form" and "Voluntary Consent Form". Baby massage training will be given to the experimental group, and a reminder training will be given 2 weeks later. "Personal Information Form", "Prenatal Attachment Inventory" and "Beck Depression Inventory" will be applied to both groups at the beginning of the study, and postpartum 30‐42 weeks. and 60‐72. "Maternal Attachment Scale" and "Edinburg Postpartum Depression Scale" will be administered between days.

Nct (2023). "The Effect of Education Given According to the Health Promotion Model on Premenstrual Symptoms, Emotional Eating Behavior and Perceived Stress." ClinicalTrails.gov.
	Changes that gradually disappear with the onset of menstruation in women are called premenstrual syndrome.In this syndrome, anxiety, irritability, lack of concentration, depression, mood swings, drowsiness, sleep disturbance, breast tenderness, appetite change, bloating, headache, weight gain, abdominal pain, fatigue and gastrointestinal symptoms are observed. Since these symptoms negatively affect both the work and personal lives of women, safe and effective treatments are needed. In this case, many women report using exercise as a strategy to help them cope with PMS, and exercise is often recommended for symptom management.PMS can also play a role in symptoms by affecting the individual's food choices. Emotional eating behavior is defined as a person's use of food as an escape from negative emotions and can lead to many conditions such as obesity, eating disorders and hormonal problems. Health promotion means increasing one's control over one's health by improving one's own health. It enables the individual to improve their physical and social environment, change their behavior, and reach the best level of physical and mental health. Philips 66 technique is a process based on active learning, problem and collaborative learning theory, student‐centered, and uses the best learning techniques to improve students' performance and realize meaningful learning activity. It is among the responsibilities of healthcare personnel to identify the factors that negatively affect women's lives in order to ensure continuity of health, ease of premenstrual symptoms, and to use the findings to improve women's health. Nurses have important duties in this regard due to their roles such as health education, health protection, development and consultancy. In this study, it is thought that the training given according to the health promotion model will both create a resource for nurses and contribute to the literature with the results obtained by applying this training to people experiencing PMS.Nurses have important duties in this regard due to their roles such as health education, health protection, development and consultancy.In this study, it is thought that the training given according to the health promotion model will both create a resource for nurses and contribute to the literature with the results obtained by applying this training to people experiencing PMS.The research will be conducted as a pretest‐posttest randomized controlled study. H1: Education given according to the health promotion model has an effect on premenstrual symptoms, emotional eating behavior and perceived stress. H0: Education given according to the health promotion model has no effect on premenstrual symptoms, emotional eating behavior and perceived stress. The total number of students in the research population is 330.In the G*Power 3.1.9.7 program, for the effect size t test, d = 0.94, alpha (α) = 0.05, and power (1‐β) = 0.95, and the minimum total sample number was determined as 52, experimental group: 26, control group: 26. . However, taking into account the losses in the study, a total of 60 people will be included in the study. (experiment:30, control:30). The first group will be divided into the group trained according to the health promotion model using the Philips 66 technique, and the second group will be divided into the control group.In the first stage, the "Premenstrual Syndrome Scale" will be applied to the students and the students will be placed in the experimental and control groups. In the second stage, Personal Information Form, PMS Scale, Premenstrual Eating Habits Form, Healthy Lifestyle Behaviors Scale, Emotional Eating Scale, Perceived Stress Scale and Visual Vissual Pain Scale will be applied to the students in this group before training. Data will be collected by face‐to‐face research method. Premenstrual syndrome periods will be determined by creating a menstrual cycle calendar for the participants. In the third stage, students in the experimental group will be trained with the first powerpoint presentation. Then br hures will be distributed. It will be applied according to the Philips 66 technique. In the fourth stage, 4 weeks after the first training, general reminder training will be given online during students' pms periods. In the fifth stage, 4 weeks after the second training, survey forms will be filled out by the experimental group and the control group.

Nct (2023). "The Effect of Education Given to Women on Cervical Cancer on Knowledge, Attitude and Belief." ClinicalTrails.gov.
	Aim: The aim of this study is to reveal the effect of education given to women about cervical cancer on knowledge, attitude and belief. Material and Method: This randomized controlled study was conducted with 130 who had a public hospital located in Southeast Turkey (51 experimental, 51 control). In the first stage, the researcher participants were informed about the purpose of the researcher and the questionnaire, and their consent was obtained for participation in the study. In the second stage, pre‐test data will be obtained with the face‐to‐face interview method of the research data and a questionnaire form. Cervical cancer education will be provided. (The training is in three sessions, each session will last 20‐30 minutes. In the training; Cervical cancer, ppt presentation on HPV virus, question‐answer method, female pelvic anatomy on the gynecological examination model, gynecological examination, how the Pap Test is done, and cervical cancer pathologies. will be explained )) After the training, the post‐test data will be obtained by applying the questionnaire again.

Nct (2023). "The Effect of Emotional Freedom Technique on Menopausal Symptoms, Quality of Life and Depression Level." ClinicalTrails.gov.
	Objective: The aim of the study was to determine the effect of emotional freedom technique (EFT) on menopausal symptoms, quality of life and depression level. Materials and Methods: This randomized controlled trial will be conducted with a total of 105 menopausal women at Fırat Family Health Center and Göztepe Family Health Center between January 2024 and June 2024 (53 EFT, 53 music, 53 control). EFT and Sham EFT will be applied in the study. Women in the EFT group will receive EFT four times at one week intervals. Women in the Sham EFT group will receive Sham EFT four times with one week intervals. Before the applications, pre‐test data will be obtained by filling out the Personal Information Form, Perimenopausal Depression Scale, Menopause Specific Quality of Life Scale and Menopause Symptom Assessment Scale before the application of Emotional Freedom Technique. After the applications, post‐test data will be obtained by filling out the Perimenopausal Depression Scale, Menopause Specific Quality of Life Scale and Menopause Symptom Assessment Scale. In addition, the Subjective Units of Experience (SUE) scale will be applied before and after each EFT intervention.

Nct (2023). "EFFECT OF EMOTIONAL FREEDOM TECHNIQUE ON PREMENSTRUAL SYNDROME." ClinicalTrails.gov.
	PMS is one of the common menstrual disorders affecting many young women, and according to epidemiological data, approximately 75% of women have PMS symptoms and 3‐8% have severe PMS symptoms. The prevalence of PMS was different in different countries, with 34% in China , 72% in Turkey , 80% in Pakistan and Jordan. It was detected in the range of 92% in India and 14.3%‐74.4% in India. Common premenstrual symptoms include anxiety, lack of concentration, depression, bloating, abdominal cramps, breast tenderness, anger, general body pain, nausea, vomiting, fatigue, decreased concentration, mood swings, headache, anxiety, sleep disturbance, appetite changes. In addition to physical symptoms, studies indicate that individuals reporting PMS experience more stress and anxiety, and their sensitivity to depressive symptoms increases due to hormonal fluctuations. Studies have shown that mindfulness‐based cognitive methods are effective in the treatment of mood disorders such as depression. It is thought that modulating many PMS symptoms such as stress and experienced emotional problems through mindfulness‐based cognitive methods may be an effective approach for future PMS interventions.

Nct (2023). "Effect of Emotional Freedom Technique on Symptoms in Dysmenorrhea." ClinicalTrails.gov.
	Primary dysmenorrhea, the most common form of dysmenorrhea, is a problem characterized by pain that begins in the lower abdomen before or with menstruation, lower back pain and pain radiating to the legs. The Emotion Freedom Techniqu has become a manualized method that has led to uniform application research, education, and clinical practice. EFT is a brief intervention that combines exposure, cognitive therapy, and somatic stimulation of acupressure points on the face and body. It has been reported in the literature that EFT, a "needle‐free and emotional" form of acupuncture, reduces or eliminates dysmenorrhea symptoms and premenstrual complaints.

Nct (2023). "Effect of Hegu Point Ice Massage and Music in Dysmenorrhea." ClinicalTrails.gov.
	Dysmenorrhea, a gynecological health problem that is frequently observed in adolescents and young adult women and often cannot be diagnosed, is defined as pelvic pain associated with menstruation. The prevalence of dysmenorrhea is reported to vary between 50% and 90% in women of reproductive age. Dysmenorrhea and the symptoms accompanying dysmenorrhea cause significant economic losses by leading to both work and school absenteeism. Particularly in adolescents, due to dysmenorrhea, participation in sports and social activities is restricted, indicators of academic performance such as school absenteeism, school success, concentration, productivity are negatively affected, and thus their levels of general comfort and quality of life decrease. On the other hand, pharmacological treatment options used in the treatment of dysmenorrhea are very few. On top of this, the effectiveness of these treatment options is still debated. Since the medication used in the pharmacological treatment of dysmenorrhea has various side effects, using non‐pharmacological treatments in addition to pharmacological treatment in the management of dysmenorrhea would be beneficial. Cold application is one of the effective, simple, inexpensive and reliable non‐pharmacological methods used to reduce pain, with few complications or no side effects. The Hegu point, the most important pain relief point of the body, can be stimulated in all painful conditions. Another low‐risk and low‐cost nonpharmacological method for standard care used in pain management is the music medicine. This randomized clinical trial was designed to determine the effects of ice massage applied to the Hegu point and music on dysmenorrhea, compared to a control group that no intervention in women of 18 years or older from the the Faculty of Health Sciences at the Manisa Celal Bayar University, Manisa, Turkey.

Nct (2023). "The Effect of Incontinence Program Applied to Obese Elderly on Quality of Life, Coping and Loneliness." ClinicalTrails.gov.
	Worldwide, there is a transition from a young population structure to an aging population structure, and life expectancy at birth is increasing. As the global growth of the elderly population will continue, we are moving towards an aging world. According to the World Health Organization, it is estimated that the population aged 60 and over will reach 2 billion by 2050. With increasing age, changes occur in every system in the body. One of these systems is the urinary system. UI suggests that it may be an early marker of the onset of frailty. In the elderly; UI is expressed as the 4th most disturbing disease after angina, difficulty in ambulation and psychiatric disorders. Among the UI subtypes, stress urinary incontinence and urge urinary incontinence are the most common and urge urinary incontinence is seen especially in the elderly. UI occurs as a result of deterioration in pelvic floor structure functions.Obesity is the best known and potentially the most modifiable risk factor for the development of UI, leading to pelvic floor deficiencies. There is a strong and positive relationship between obesity and urinary incontinence. Compared with patients of normal weight, obese patients are approximately twice as likely to present with urinary incontinence. Individuals may experience physical and psychosocial limitations due to UI, and their quality of life may be adversely affected. As a result of this situation, anxiety, depression, deterioration in sexual life, decrease in physical activity, loss of self‐confidence and social isolation problems can be seen. All these conditions are in themselves associated with poor quality of life. Urinary incontinence is rarely reported, especially in older adults, as it is believed to be a natural consequence of aging and that there is no clear management approach or cure. Therefore, individuals with UI do not seek help from family members or healthcare providers for urinary incontinence symptoms for various reasons. However, despite experiencing urinary incontinence, people may not seek treatment for reasons such as ignorance, ignorance, not being able to find time to go to the doctor, thinking about urinary incontinence as normal, or rejecting or hiding incontinence. Individuals with urinary incontinence do not seek help and try to cope with this problem on their own. UI that negatively affects psychological and social well‐being and quality of life; Decreased self‐confidence of the individual brings along problems such as living alone and escaping from society. Individuals sometimes reduce or avoid social contacts and activities to control UI. This leads to increased social isolation and feelings of loneliness. It is stated that conservative treatment methods can be used in the first‐line treatment of urinary incontinence. In the guidelines of the European Association of Urology, it is emphasized that conservative treatment methods of urinary incontinence should be used as the first choice in the treatment of patients. Conservative treatment methods include lifestyle changes (weight loss, smoking cessation, diet regulation, regulation of fluid consumption), behavioral treatments, and pelvic floor muscle training. Among these methods, pelvic floor muscle exercises come to the fore. In the treatment of urinary incontinence of the frail elderly, pelvic floor exercises are included in the first‐line treatment. Incontinence is also related to nutrition. Nutrition can affect lower urinary system functions. In order to prevent or reduce UI, the European Urology Association 2020 guideline states that different lifestyle practices, such as reducing caffeinated beverages, regulating fluid intake, and quitting smoking, together with weight loss, have an effect on UI symptoms. Some exercises can reduce urinary incontinence symptoms. Characterized by a gentle/gentle, slow and coordinated sequence of movements, Tai‐Chi exercise is a suitable form of exercise for older adults as it involves minimal strain on the joints and cardiovascular system. Tai chi e ercise is an easy‐to €learn and ubiquitous exercise recommended for both men and women in conditions related to the pelvic area and for improving health in the elderly. In one study, Tai Chi improved the quality of life of elderly women with overactive bladder syndrome, emergency urinary incontinence. In another study, it was found that men with lower urinary tract symptoms performed tai chi and a significant result was obtained compared to men without lower urinary tract symptoms. Health‐promoting measures for older adults with UI are necessary to maintain their well‐being and prolong healthy life expectancy. It will be important to create a training component/plan for this. Considering learning principles in planned adult education activities can contribute to the formation of an effective learning environment for adults. Knowles brought a different and systematic perspective to the subject of adult learning. In this context, training components can be prepared according to Knowles' adult learning principles. It is recommended to use some models and theories, especially behavior modification theories, for those with incontinence problems to acquire healthy lifestyle behaviors. Health Belief Model (SIM) is one of the best models that can be used to develop knowledge, attitudes, beliefs about urinary incontinence and to create behavior towards kegel exercise, which is one of the effective methods in preventing urinary incontinence. Studies for the prevention of urinary incontinence are limited in the literature, and interventional studies based on a theoretical background have not been found. In this study, the Incontinence Management Program based on Knowles' Adult Learning Principles and Health Belief Model will be used. According to Knowles' Adult Learning Principles, which gives a different and systematic perspective to adult learning, no national or international study on obese elderly people has been found in the literature. At the same time, although SIM is used for more than one disease and various studies have been conducted, no study has been found to strengthen the motivation to change behavior in order to ensure continuity for obese elderly people. In addition, no study has been found in the literature in which the effectiveness of an education in which lifestyle behaviors based on Knowles' Adult Learning Principles and Health Belief Model, Kegel exercises and Tai Chi exercises are applied in the management of UI.

Nct (2023). "The Effect of Interactive Music Therapy Applied for Women During the Perioperative Period for IVF on Their Stress Levels." ClinicalTrails.gov.
	If the patients participate in the study, when they apply to the in vitro fertilization center, they will meet with their anesthesiologist, anesthesia assessment will be done face to face and asked some questions about the diseases that may affect the procedure. . If patients are included in the study, their blood pressure, blood oxygen value and heart rate will be measured and recorded, as in every patient. Subsequently, a test will be administered to assess stress and anxiety levels of the patients. The patients involved in the study will be randomly divided into two groups. One group will be provided with a set of headphones that completely cover the ears and will be played their selected music from a predetermined album for 20 minutes before the procedure. The music will continue to be played through the headphones during the procedure. The other group will be taken to the operating room without any procedure, and this process will be applied to both groups. When patients are brought to the operating room, blood pressure, blood oxygen levels, and heart rate will be measured and recorded once again. Routine anesthesia procedures, applicable to all, will be carried out. After patients are fully awake, their pain condition will be assessed using a visual test.

Nct (2023). "Effect of Lactobacillus Johnsonii or White Pomegranate Extract on the Vaginal Health." ClinicalTrails.gov.
	This study is an interventional trial conducted in a randomized double‐blind controlled study, we will recruit 150 participants. Participants will be randomly d divided into three groups (Group A: Placebo; Group B: heat‐killed Lactobacillus johnsonii TCI250; Group C: White pomegranate extract, dosage of 500mg) for 8 weeks. Subsequently, participants will be followed up for an additional 8 weeks to observe changes in the vaginal microbiota and inflammation. At weeks 0, 4, 8, and 16, participants will record basic information such as personal dietary habits, lifestyle, and health conditions. Additionally, vaginal epithelial cells and whole blood (5 mL) will be collected at weeks 0, 8, and 16 for liver and kidney function monitoring (GPT, creatinine). 1. Study Participants i. Inclusion Criteria (1) Females aged 20‐45 (2) Nugent score ≥ 4 (3) Menstrual cycle of 28‐60 days ii. Exclusion Criteria (1) Pregnant or lactating women (2) Antibiotic usage (3) Other reproductive‐related inflammatory diseases (e.g., candidiasis, gonorrhea, chlamydia infection) (4) Allergy to probiotics or White Pomegranate‐related components iii. Withdrawal Criteria Participants are free to decide whether to participate in this trial, and they can withdraw their consent at any time during the trial without providing any reason. If participants experience discomfort, they may withdraw from the trial at any time without facing any penalties or compromising their rights. 2. Subject Recruitment Interested participants will be recruited openly through posters posted at Chung Shan Medical University Hospital. The researchers will explain the trial content for 15‐20 minutes, and if interested, participants will sign the informed consent form. 3. Research Methods i. Questionnaire assessment ii. Nugent score evaluation iii. Inflammatory markers detection: Including IL‐4, IL‐10, IL‐6, IL‐8, MCP‐1, TNF‐α, IL‐1β. I iv. Microbiota gene sequencing: Utilizing 16S rRNA gene sequences to analyze the vaginal microbiota. 4. Statistical Methods Data from this study will be analyzed using SigmaPlot statistical software (version 12.5; Systat Software, San Jose, CA) and SAS statistical software (version 9.4, Statistical Analysis System Institute Inc., Cary, NC, USA). One‐way ANOVA will be used to compare differences among the three groups, repeated measurement ANOVA to compare pre‐ and post‐intervention values within each group, and multiple linear regression to analyze the impact of supplement intake on vaginitis scores, inflammation, and microbiota diversity. The results will be presented as mean ± standard deviation (SD). Statistical significance will be indicated by p < 0.05. Through this study, the administration of Lactobacillus johnsonii TCI250 probiotics and White Pomegranate extract is investigated for their effectiveness in improving the vaginal microbiota in women. This could potentially serve as a means of promoting vaginal health and well‐being.

Nct (2023). "The Effect of Laughter Yoga on Premenstrual Symptoms and Quality of Life in Midwifery Students." ClinicalTrails.gov.
	59 midwifery students will participate in the research. In this study, the number of laughter yoga sessions was determined in line with the studies in the literature. Each laughter yoga session is planned to last approximately 40‐45 minutes. Each session of laughter yoga consists of clapping and warm‐up exercises, deep breathing exercises, childlike play and laughter.

Nct (2023). "The Effect of Laughter Yoga on the Stress Levels of Infertility Women." ClinicalTrails.gov.
	This research is a randomized controlled study to evaluate the effect of Laughter yoga on the stress levels of infertility women. At the beginning of the study, necessary ethics committee permission and institutional permissions were obtained. Both of the researchers have a certificate of leadership in laughter yoga. As a result of the power analysis, it was determined that 80 women should be included in the study. Considering that there may be losses, it was decided to include 90 women in the study. By providing randomization, 90 women who met the sampling criteria and volunteered to participate in the study were divided into two groups as 45 experimental and 45 control. At the beginning of the study, the Infertility stress scale was applied to women in both groups to determine their stress levels. Afterwards, 8 sessions of laughter yoga were applied to the experimental group for 4 weeks, two sessions a week. No application was made to the control group. After 4 weeks, the Infertility stress scale was administered to the women in both groups to re‐determine their stress levels.

Nct (2023). "The Effect of Low Doses of Prednisone on the Prolongation of Pregnancy in Threatened Preterm Birth." ClinicalTrails.gov.
	Prematurity is the leading causes of infant mortality and is associated with an increased risk of respiratory, neurological and metabolic disorders in survivors. Approximately 15 million babies are born preterm annually worldwide. Despite the rapid development of pharmacotherapy, there was no significant decline in the premature birth (PTB) rates. So far, the most useful intervention for improving neonatal outcomes in premature children has been the antenatal administration of long‐acting corticosteroids (CSs). Although the underlying causes of PTB are numerous, it is well established that infection and inflammation represent a highly significant risk factor for spontaneous PTB, characterized by the significant production of inflammatory mediators that lead to weakening of the foetal membranes, cervical stroma and contraction of the myometrium. There is increasing evidence of the presence of sterile inflammation (intra‐amniotic inflammation without the presence of microorganisms) in PTB with both intact membranes and preterm premature rupture of membranes (PPROM). CS and non‐steroidal anti‐inflammatory drugs (NSAID) are used today to treat most inflammatory diseases. NSAID are used as tocolytics. Indomethacin, one of the most commonly used NSAID tocolytics has been associated with oligohydramnios and premature closure of the foetal ductus arteriosus when used for prolonged period. As far back as 1972, Liggins and Howie proved that antenatal administration of CS reduces the incidence and severity of respiratory distress syndrome (RDS) and mortality of premature infants. Meta‐analyses have confirmed a lower rate of intraventricular haemorrhage and necrotic enterocolitis in premature infants whose mothers received RDS prophylaxis. Therefore, their application proved to be the most useful intervention for improving neonatal outcome in threatening PTB.Today, a CS is a part of standard therapy for the treatment of systemic autoimmune diseases and act as suppressors of immune response. Long acting CSs cross the placental barrier and are used to treat the foetus (foetal lupus, congenital adrenal hyperplasia, prevention of respiratory distress syndrome), and intermediate acting drugs are used to treat maternal diseases as they have a low affinity for passing through the placenta.The effect of low doses of intermediate acting corticosteroids on the prolongation of pregnancy in threatened preterm birth has not yet been studied.Given that PTB is a syndrome characterized by a strong inflammatory response, we present the hypothesis that low doses of an intermediate acting CS for 3 weeks after tocolysis and RDS prophylaxis help prolong singleton pregnancy in women with threatening PTB, without harmful consequences for mother and child.

Nct (2023). "Effect of Lumbar Proprioception Training on Primary Dysmenorrhea." ClinicalTrails.gov.
	Although previous studies reported the effect of physiotherapy practices through therapeutic exercises on primary dysmenorrhea as core muscles strengthening, core stability exercises, connective tissue massage and classical massage, relaxation, strengthening, stretching, aerobic exercises, pelvic floor muscle strengthening exercises, yoga and Pilates. None of them have investigated the effect of lumbar proprioception training on primary dysmenorrhea. Therefore, this study will be the first one which aims to investigate the effect of lumbar proprioception training on primary dysmenorrhea. This trial will include 2 groups; group A composed of 20 females that will receive hot packs and pelvic rocking exercises for 4 weeks and group B also composed of 20 females that will receive hot packs and pelvic rocking exercises in addition to lumbar proprioception training for 4 weeks.

Nct (2023). "The Effect of Mandala Art Therapy in Coping With Premenstrual Syndrome." ClinicalTrails.gov.
	Materials and Methods: The randomized controlled trial was conducted between October 2022 and April 2024 with 120 students (60 intervention group and 60 control group) studying at Kahramanmaraş Sütçü İmam University and Gaziantep Islamic Science and Technology University, Faculty of Health Sciences, Department of Midwifery. In the study, mandala art therapy is applied to the students in the intervention group. The students will be informed about the method to be followed in the research, the voluntary information form will be read to those who want to participate in the research, and their verbal and written permission will be obtained. Before the mandala art therapy, Personal Information Form, Premenstrual Syndrome Scale (PMSS), Coping with Premenstrual Change Scale, Perceived Stress Scale, Beck Depression Inventory will be applied to the students in both groups. The students in the intervention group will be given mandala activity by the researcher two days a week for 12 weeks/total 24 times. Three months after the first interview, Premenstrual Syndrome Scale (PMSÖ), Coping with Premenstrual Change Scale, Perceived Stress Scale, Beck Depression Inventory will be administered as a post‐test. One month after the end of the study, Premenstrual Syndrome Scale (PMS), Coping with Premenstrual Change Scale, Perceived Stress Scale, Beck Depression Inventory will be administered again as follow‐up assessment. The materials such as drawing paper, drawing and crayons required for mandala drawing in the study were provided by the researchers.

Nct (2023). "The Effect of Mobile-Based Education Given to Patients Undergoing Gynecological Oncology Surgery on Quality of Life." ClinicalTrails.gov.
	Power analysis was conducted to determine the number of people to be included in the study. The power of the test was calculated with the G*Power 3.1 program. As a result of the power analysis, the sample size should be 50, 25 experimental and 25 control groups, at 95% power, 5% significance level, and 0.690 effect size (df=24; t=1,710). In the research, it was aimed to reach a total of 70 women, 35 people in each group, considering the high power of the test and the losses. Introductory Information Form, Symptom Evaluation Form, Functional Assessment of Cancer Therapy‐General (FACT‐G) and Turkish‐Computer System Usability Questionnaire (T‐CSUQ‐ SV) planned to be used as data collection tools in the study. The women included in the study sample will be divided into two groups as experimental and control groups according to randomization. Experimental group; the group to be trained. control group; This is the group in which no attempt will be made other than data collection. Statistical Analysis of Data: The data obtained in the research will be analyzed using SPSS (Statistical Package for Social Sciences) for Windows 25.0 program. Homogeneity of descriptive features between groups will be tested by chi‐square analysis and independent group t‐test. The differentiation status of the scales between the groups will be analyzed with the independent group t‐test and the changes within the group will be analyzed with the repeated measures ANOVA test.

Nct (2023). "The Effect of Peer-Guided Pilates Exercise on Premenstrual Syndrome Symptoms and Healthy Lifestyle Behaviors: a Randomized Controlled Study." ClinicalTrails.gov.
	This project is to examine the effect of pilates exercise, which is applied by university students under the guidance of peers, on premenstrual syndrome symptoms and healthy lifestyle behaviors. Methods: The research to be carried out within the scope of the project is randomized controlled and has an experimental research design. The population of the research consists of 385 female students studying at the Department of Midwifery at Istanbul University‐Cerrahpaşa Faculty of Health Sciences. In the study, it is aimed to reach all students without making a sample calculation in order to identify the students with PMS symptoms among all students. Students who score 110 and above on the Premenstrual Syndrome Scale (PMSS) will be considered to have PMS symptoms. The sample size of the students showing PMS symptoms was determined by using the G*Power (3.1.9.2) program and considering the 0.05 margin of error and data loss, according to 95% power and medium effect size; 27 people should be included in the experimental group and 27 people in the control group. In determining the groups, the participants will be assigned to the experimental and control groups using the "Randomizer.org" program. Students included in the research will be given information about the study and will be presented with an "Informed Consent Form" and a "Volunteer Consent Form". While the experimental group will be given pilates exercises, under the guidance of a peer, for half an hour twice a week for six months, the control group will maintain their routine habits. At the beginning of the study, data will be collected with the "Personal Information Form", "Premenstrual Syndrome Scale (PMSÖ)" and "Healthy Lifestyle Behaviors Scale‐II (SYBDS‐II)". In the third and sixth months of the study, the hypotheses will be tested by applying PMSS and HLBS‐II. The data obtained in the research will be entered into the database in the IBM SPSS 25.0 (Statistical Package for the Social Sciences) program and all necessary statistical analyzes will be performed in the same program.

Nct (2023). "Effect of Progressive Muscle Relaxation Exercises in Menopausal Women Experiencing RLS." ClinicalTrails.gov.
	Menopause, which is a natural part of women's life; It is a condition that occurs between the ages of 45‐52 on average and is characterized by hormonal changes and cessation of the menstrual cycle. Many symptoms are observed during menopause, such as hot flashes, sleep problems, mood disorders, sexual dysfunction, weight gain, and decline in cognitive functioning. Restless legs syndrome is another symptom that can be seen in all periods of a woman's life, but its frequency and severity increases with menopause. Restless legs syndrome is a neurological problem that occurs usually at night with an irresistible urge to move the legs. There are studies reporting that sleep problems, which are a common problem during the menopausal period, worsen with the addition of restless legs syndrome. Restless legs syndrome and sleep problems are two important factors that negatively affect the quality of life of women in the menopausal period. Alternative and complementary therapies are frequently used among the methods used to cope with menopausal symptoms and symptoms triggered by menopause. These methods include hypnosis, body‐mind techniques, cognitive behavioral therapies, aromatherapies, and herbal supplements. It is stated that these techniques reduce the stress of women in the menopausal period and are effective in improving their quality of life. One of these methods is progressive muscle relaxation exercise. Progressive muscle relaxation exercise is a systematic practice that aims to provide deep relaxation by exercising large muscle groups in the body along with breathing techniques. There are studies reporting that PCGE is used effectively in coping with menopausal symptoms. This study aims to evaluate the effect of progressive muscle relaxation exercise on the severity of restless legs syndrome, quality of life and sleep quality related to restless legs syndrome in menopausal women with restless legs syndrome.

Nct (2023). "Effect of Propolis Administration for Dysmenorrhea in Endometriosis Patient With Levonorgestrel Implant Therapy." ClinicalTrails.gov.
	The goal of this clinical trial is to investigate the effect of propolis administration on dysmenorrhea in endometriosis patient. the main questions it aims to answer are: ‐ Does the propolis administration reduce symptoms of dysmenorrhea in endometriosis? ‐ Does the propolis administration reduce the amount of oxidative stress biomarkers in endometriosis? ‐ Does the propolis administration reduce the amount of Inflammatory biomarkers in endometriosis? Participants will be given an intervention in the form of propolis at a dose of 1 drop per 10 kilogram of body weight per administration, twice a day. there will be a control group that will be given an intervention in the form of a placebo containing 70% caramel alcohol dye solution.

Nct (2023). "Effect of Quercetin Supplementation on Endometriosis Outcomes." ClinicalTrails.gov.
	The participants in the study were randomly assigned to two groups: the intervention group and the control group. The intervention group will receive two 500 mg quercetin tablets daily, after breakfast and lunch, for twelve weeks. On the other hand, the control group will be given a placebo. Blood samples will be collected before and after the intervention to measure changes in blood lipid profile, fasting blood sugar, sex hormones (testosterone, estrogen, progesterone), TNFα, IL‐6, adiponectin, IGF1, HbA1C, SHBG, FSH, LH, and plasma total antioxidant capacity.

Nct (2023). "The Effect of Reiki on Pain, Stress and Comfort Level in Students Experiencing Dysmenorrhea." ClinicalTrails.gov.
	Hypotheses 01; there was no difference between the pain score of the reiki group and the pain score of the control group. H02; there was no difference between the stress score of the reiki group and the stress score of the control group. H03;there was no difference between the comfort level of the reiki group and the comfort level of the control group. The study will be carried out in two different groups. The practice will start with meeting the students who experienced dysmenorrhea. After the women are evaluated in terms of eligibility criteria for the research, the women who are eligible will be informed about the research and written informed consent will be obtained from the women who accept. The random distribution of women to the study groups will be carried out using the Block Randomization method. The following applications will be made to the groups. Reiki Group The intervention will be applied to the reiki group to be applied in the midwifery department application laboratory. Reiki therapy will be applied by a practitioner with a Reiki application certificate in the application laboratory for 30 minutes while the participants lie down with their eyes closed. 4 sessions of reiki application will be applied to the intervention group for a month. Reiki application will start from the time of menstruation, the first pain scores and comfort conditions will be recorded. Menstruation and general comfort after 4 sessions will be recorded. Any medication and side effects during menstruation with the last reiki application will be recorded by the research team member. Placebo Reiki will be applied to the participants in the group in the application laboratory of the midwifery department of the faculty of health sciences. The practice will be carried out in the application laboratory for 30 minutes, with the participants sitting with their eyes closed. Reiki life energy will not be transferred to participants in the placebo reiki group. Since the participants' eyes are closed, they will not know that there is a transfer. Placebo Reiki application will be performed in the laboratory 4 times during a month. Placebo application will start from the time of menstruation, and the first pain scores and comfort conditions will be recorded. After 4 sessions, menstruation and general comfort will be recorded. Any medication and side effects during menstruation with the last application will be recorded by the research team member.

Nct (2023). "Effect of Sage Essential Oil Inhalation Aromatherapy on Premenstrual Symptoms and Quality of Life." ClinicalTrails.gov.
	In premenstrual symptoms, psychotropic drugs, hormone therapy or nonsteroidal anti‐inflammatory drugs are used as pharmacological methods. Aromatherapy, which is one of the non‐pharmacological methods, is preferred to reduce premenstrual symptoms. Aromatherapy through massage and inhalation is commonly used in nursing interventions. Sage has also been used for various human ailments since ancient times. Sage oil regulates the menstrual cycle and hormonal components and is known to alleviate climatic changes and symptoms in menopausal women. The main goal of nursing practices is to ensure the well‐being of the individual, family and society, to maintain care, to organize attempts to protect and improve health, to teach coping methods for healing and rehabilitation in case of illness, and is to increases the quality of life. From this point of view, studies have shown that aromatherapy has an effect on reducing premenstrual symptoms and increasing quality of life. This research, It is thought that it will both create a resource for nurses and contribute to the formation of the necessary evidence for the application of sage oil in aromatherapy in people with PMS.

Nct (2023). "Effect of Sitagliptin on Polycystic Ovarian Syndrome Patients." ClinicalTrails.gov.
	Study Design : a Prospective Randomized Controlled Trial. A Total of 80 infertile Adult Females aged between 18 and 45 years currently diagnosed with Polycystic ovary syndrome , Meeting the Diagnosis of Rotterdam criteria be diagnosed if any two of the following are present: (1) clinical or biochemical hyperandrogenism, (2) evidence of oligo‐anovulation, (3) polycystic appearing‐ovarian morphology on ultrasound are to be included in the study. The study will include two groups; each group consists of 40 patients:‐ Group A : Control Group Group B : Test Group ( will Receive Sitagliptin at a dose of 100 mg every 24 hours

Nct (2023). "The Effect of the Hand Massage A Women Undergoing Brachytherapy." ClinicalTrails.gov.
	Therefore, the impact of hand massage applied with lavender baby oil on women with gynecologic cancer having brachytherapy for three sessions on the pain and state anxiety experienced during the intervention was evaluated in this study.

Nct (2023). "The Effect of the Self-Care Support Program on Women With Endometriosis." ClinicalTrails.gov.
	This study is a randomized controlled experimental study conducted to evaluate the effect of self‐care support program applied to women with endometriosis on quality of life, self‐care behaviors, depression, anxiety and stress levels.The research was carried out with the participation of two groups. Endometriosis Self‐care Support program‐ESSP (intervention group) will be applied to one of the groups, while the other group (control group) will receive standard treatment within the scope of the hospital protocol. Then, women's quality of life, self‐care behaviors, depression, anxiety and stress levels will be evaluated.

Nct (2023). "Effect of TTNS and PNS on Neurogenic Overactive Bladder Symptoms in Female Patients With Multiple Sclerosis." ClinicalTrails.gov.
	Participants will be divided into 3 groups: TTNS, PNS, and placebo groups, and all participants will be given behavioral treatment. Tibial nerve stimulation will be given to the TTNS group, sacral nerve stimulation will be given to the PNS group, and sham current will be given to the placebo group. Stimulation treatments will be applied 2 days a week for 30 minutes each for 6 weeks. Participants will be evaluated before and after treatment. The parameters of urination frequency, urgency, and urinary incontinence will be evaluated with a 3‐day voiding diary (BD), maximum flow rate (Qmax), time to reach maximum flow (TQmax), average flow rate, flow time (Tw), voiding time and voiding volume (VV) values will be evaluated by uroflowmetry, post‐voiding residual (PVR) volume will be evaluated by ultrasound, and quality of life will be evaluated by King's Quality of Life Questionnaire (KHQ); Expanded Disability Status Scale (EDSS), Overactive bladder form (OAB‐v8), Incontinence Severity Index (ISI), Neurogenic Bladder Symptom Score (NBSS) will be recorded.

Nct (2023). "Effect of Video-based Exercise on Premenstrual Symptoms: a Randomized Controlled Trial." ClinicalTrails.gov.
	The research is a quantitative study, and it is in the form of randomized controlled type research, one of the experimental research types. The sample of the study consisted of people who scored above the mild level according to the Premenstrual Syndrome Scale (PMSS) score and volunteered to participate in the study. Participants will be divided into 2 groups as experimental group and control group by randomization method. Sociodemographic Information Form, Premenstrual Syndrome Scale (PMSS), Perceived Stress Scale (PSS) and Mcgill Melzack Pain Scale (MPQ) will be administered to the participants. Pre‐ and post‐intervention data were statistically analyzed and compared.

Nct (2023). "Effect of Visceral vs Total Body Fat Reduction in Obese Female With Stress Urinary Incontinence." ClinicalTrails.gov.
	compare the effect of visceral fat reduction versus total body fat reduction on stress urinary incontinence in obese females. control group: consist of 20 obese women. They will receive Kegel exercises only 3 session/ week for 12 weeks. Diet group: consist of 20 obese women. They will receive low caloric diet and Kegel exercises 3 session/week for 12 weeks. Ultrasound cavitation group: consist of 20 obese women. They will receive Kegel exercises 3 session/week and ultrasound cavitation two sessions per week.

Nct (2023). "Effect of Vitamin D Supplementation on Testosterone Level in Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	PCOS poses a significant challenge to women's health and quality of life. PCOS is a common heterogenous endocrine disorder in reproductive‐aged women. PCOS is characterized by the presence of polycystic ovaries, menstrual dysfunction, infertility and biochemical (elevated androgens) and clinical (hirsutism and/or acne) hyperandrogenism. Hyperandrogenism and insulin resistance exacerbate one another in the development of PCOS, Research has suggested a potential link between Vitamin D deficiency and the prevalence and severity of PCOS. There is also evidence that Vitamin D has a direct effect on the ovaries and adrenal glands, which are the primary sites of androgen production in women. Vitamin D has been found to inhibit the synthesis of androgens in these glands, suggesting that it could potentially be used to manage hyperandrogenism in women with PCOS. Furthermore, studies have shown that Vitamin D supplementation can reduce insulin resistance in women with PCOS, which can subsequently lead to a decrease in the overproduction of androgens. may improves menstrual irregularities. In human ovarian tissue, vitamin D stimulation of oestrogen and progesterone production and lack of effect on testosterone production may be explained by the expression of the aromatase gene and augmentation of aromatase activity by vitamin D. Serum 25OH‐D level has been shown to be negatively correlated with serum androgen levels DHEAS, testosterone and hirsutism. Assumption that vitamin D supplementation may also have a positive impact on serum testosterone levels. Metformin is prescribed for reducing IR in PCOS women. This is a double‐blind, randomized placebo‐controlled trial in PCOS women who are receiving Metformin therapy. The intervention group will receive Vitamin D Cholecalciferol (D3) 1000 I.U daily for 8 weeks, with the Metformin as prescribed by the physician whereas control group will receive placebo with Metformin during the study period. We will compare change of Total Testosterone, Vitamin D level, Fasting blood glucose, Hirsutism, Menstrual regularities and BMI, at the time of recruitment with after 8 weeks intervention in both the intervention and placebo controlled groups.

Nct (2023). "Effect of Weight Reduction and Aerobic Exercise on PMS Symptoms in Obese Females." ClinicalTrails.gov.
	both groups (A&B) will take their medical treatment in the form of (NSAIDs) and the study group B will under go a siet plan which will fits the participants. Diet plan extends for 12 weeks in the form of caloric restriction program and each woman in group B will perform aerobic exercise program, in the form of treadmill 3 times/week for 8 weeks for 12 weeks. Each session will take about 30 minutes as the following: 5 minutes warming up exercises by walking on the treadmill by low speed, 20 minutes walking at moderate intensity (70% of the maximal heart rate) and 5 minutes are cooling down by walking on the treadmill by low speed as in warming up.

Nct (2023). "Effect of Whey Protein Supplementation on Postoperative Outcomes After Gynecological Cancer Surgery." ClinicalTrails.gov.
	During admission, Participants will be randomized by a computer program into two groups as the whey protein supplement group and control group. Both groups will undergo nutritional assessment on the first day of admission before surgery by the Rajavithi Subjective Global Assessment tool and serum albumin level. The whey protein supplement group : participants will receive isolated whey protein in the form of two packets of isolated whey protein powder (each packet containing 11.5 grams, totaling to 23 grams) mixed with water in a 350 milliliter drinking bottle at 6.00 p.m. on first day before operation. After the operation, participants will receive the same form of protein supplement as before surgery at 6.00 a.m. on the first day after operation. The control group : participants will receive standard care, which includes fasting from food after midnight on the night before surgery and other standard surgical protocols. After surgery, participants will be assessed based on 1. Intraoperative outcomes, which include the duration of surgery, intraoperative blood loss, and intraoperative complications. 2. The postoperative outcomes, which include length of hospital stay, duration of stay in the intensive care unit (ICU), postoperative complications, postoperative pain, time to first ambulation , time to first flatus , nausea and vomiting symptoms, increased requests for pain medication, fever more than 24 hours after surgery , wound infection and readmission. 3. The nutritional status outcomes, assessed through serum albumin levels before surgery and on the 3rd day after surgery in both groups of participants. 4. The side effects of whey protein supplement, in the experimental group participants, which will evaluate include allergic reactions, nausea, vomiting, abdominal discomfort, bloating, headache, reduced appetite, elevated creatinine levels, and increased liver function levels on the 3rd day and two weeks after surgery.

Nct (2023). "The Effectiveness of Battlefield Acupuncture (BFA) With Standard Therapy in Gynecological Cancer Pain." ClinicalTrails.gov.
	This study was conducted using a single blinded randomized control clinical trial design in 58 female patients who are hospitalized aged 18‐65 years, have a diagnosis of gynecological cancer, with a VAS score≥4 caused by tumor, before or during a therapeutic process (radiation therapy, chemotherapy, or after surgery), agree to participate in the study, sign the informed consent form who were randomized into 2 groups, namely group I BFA ear acupuncture with standard therapy and group 2 standard therapy, the acupuncture points used were placed at points MA‐IT1 Cingulate Gyrus, MA‐AT2 Thalamus, MA‐H2 Omega 2, MA‐H1 Point Zero, MA‐TF1 Shenmen on both sides of the ear using Pyonex needles were placed with a diameter of 0.17mm, depth of 0.9mm. the pyonex press needle. were retained for three days The outcome assessed were pain intensity using the VAS, changes in analgesic dose, and quality of life with the EORTC QLQ C‐30 questionnaire, which was assessed on the day before starting therapy, the first day, the second day, the third day, the fifth day and the seventh day

Nct (2023). "Effectiveness of eCoin at Sensory and Subsensory Amplitudes." ClinicalTrails.gov.
	The goal of this prospective, multi‐center, double‐blinded randomized controlled is to learn about effectiveness and QOL with eCoin at two different amplitude settings in subjects with urge urinary incontincence (UUI). The main question it aims to answer is: ‐ The reduction in UUI episodes per day on a 3‐day voiding diary in both groups after 3 months of therapy Participants will be implanted with the eCoin device and randomized to either a sensory or subsensory stimulation group and complete voiding diaries and patient reported‐outcomes through 3 months of therapy.

Nct (2023). "The Effectiveness of Electroacupuncture With Standard Therapy Compared to Standard Therapy in Gynecological Cancer Pain." ClinicalTrails.gov.
	This study was conducted using single blinded randomized control clinical trial, design in 58 patients diagnosed with gynecological cancer, aged 18 to 65 years, who experienced cancer pain, with VAS ≥ 4, pain caused by a tumor, before or while undergoing a therapeutic process (radiation therapy, chemotherapy, or post surgery), side effects or due to the toxicity of cancer treatment, willing to take part in this study and sign informed consent who were randomized into 2 groups, namely group I electroacupuncture with standard therapy and group 2 standard therapy, the acupuncture points used were LI4, PC6, ST36, SP6 and LR3, after the acupuncture needle was inserted, the needle was connected to the electrosimulator. The outputs assessed were pain intensity using the VAS, changes in analgesic dose, and quality of life with the EORTC QLQ C‐30 questionnaire, which was assessed on the day before starting therapy, the first day, the second day, the third day, the fifth day and the seventh day.

Nct (2023). "Effectiveness of Low-dose Naltrexone in Patients With Different Types of Vulvodynia." ClinicalTrails.gov.
	In this Randomized Controlled Trial the effectiveness of LDN in reducing chronic pain and improvement of quality of life in women with provoked, spontaneous or mixed vulvodynia is assessed on the basis of the test results recommended according to IMMPACT protocol, compared to the placebo arm. Patients remain in the study for 6 months (4 months of treatment with LDN or placebo). There are 5 visits by a gynecologist (diagnosis of vulvodynia, inclusion and exclusion criteria, randomization), nurse, psychologist and physiotherapist: screening, randomization, control telephone visit, final visit and telephone summary visit. Pain perception and quality of life estimation is reported by the patient in e‐diary, validated psychology questionnaires are fulfilled and physical examination acc. Fascial Manipulation (CFMS) L. Stecco method is performed. Tolerability of LDN therapy will also be assessed.

Nct (2023). "Effectiveness of Magnetic Stimulation in the Treatment of Female UUI." ClinicalTrails.gov.
	RATIONALE: The FDA approved extracorporeal magnetic stimulation as a form of conservative treatment of urinary incontinence in 1998. Since then, the studies focused mainly on magnetic stimulation's effectiveness in treating stress urinary incontinence. There are five studies that assessed the efficacy of magnetic stimulation in the treatment of urgency urinary incontinence. Only one was randomized and sham‐controlled, others were not. Three studies used urodynamic studies to assess the effectiveness of magnetic stimulation treatment, but those studies were not randomized or sham‐controlled. The EAU guidelines, therefore, do not recommend extracorporeal magnetic stimulation as a treatment option for urinary incontinence for the lack of evidence. AIM OF THE STUDY: The study will evaluate the efficacy of magnetic stimulation as a type of conservative treatment in patients with urgency urinary incontinence. After evaluating previously conducted studies, the investigators decided to conduct the first randomized, sham‐controlled study that evaluated the effectiveness of magnetic stimulation as a treatment for urgency urinary incontinence with subjective and objective measures. METHODS: the study will be randomized and sham controlled with 40 enrolled patients. The patients will be allocated in the active or sham arm in a ratio of 2:1. The patients will be recruited from the UMC Ljubljana outpatient urogynecologic clinic. All eligible patients will be invited to participate in our study by phone. STATISTICAL ANALYSES: The results will be analysed with the Kolmogorov‐Smirnov test and two‐way ANOVA with repeated measures.

Nct (2023). "Effectiveness of Manual Acupuncture and Standard Therapy Compared to Standard Therapy in Gynecological Cancer Pain." ClinicalTrails.gov.
	The main outcome is to analyze the effectiveness of manual acupuncture therapy (LI4,PC6, LR3,ST36, and SP6 plus standard therapy on pain intensity (VAS score), changes in analgesic dose, and quality of life (QLQ C‐30 EORTC score) in patients with gynecological cancer pain compared to standard therapy alone. The patient will attempt 3‐day manual acupuncture therapy with seven days follow up Patient will receive acupuncture therapy daily for 3 days, for 15 minute each day. The research design in this study was a single‐blinded randomized control clinical trial. With outcome measures for With Subject criteria: Inclusion Criteria 1. The patient is diagnosed with gynecological cancer 2. Women over 18 years to 65 years 3. Subjects experiencing cancer pain, with VAS ≥4, namely pain caused by: ‐ tumors, ‐ before or during a therapeutic process (radiation therapy, chemotherapy, or post‐surgery) ‐ side effect or the result of toxicity of cancer treatment ‐ Supportive therapy (palliative therapy, painkillers, antidepressants) 4. Willing to participate in this study and sign an informed consent Exclusion Criteria 1) The patient has a medical emergency / hemodynamically unstable 2) Patients with contraindications for manual acupuncture procedures such as wounds and infections at the point where the puncture will be performed, patients allergic to stainless steel62 3) Uncooperative patients (patients with negative and aggressive affect, who do not allow acupuncture therapy) 4) There is a tumor in the area that will be stabbed and stimulated in the pregnant woman's abdomen, close to the heart, or around the carotid sinus, lymphedema, needle insertion into the prosthesis 5) Patients with heart rhythm disorders 6) The patient uses a pacemaker 7) Patients with disorders of the auricle such as eczema, external otitis, and psoriasis 8) Patients with blood clotting disorders, with platelets <50,000, and in neutropenic conditions with neutrophils <1000

Nct (2023). "Effectiveness of Oral Boldo in Women With Overactive Bladder." ClinicalTrails.gov.
	10 women over 18 years of age who meet the selectivity criteria will be recruited under written informed consent, previously approved by the competent ethics committee. Patients will be diagnosed with overactive bladder through a clinical interview and a voiding record performed by a specialist urologist that may or may not be confirmed by a urodynamic study. Prior to carrying out the tests, the informed consent will be read aloud to the patient by one of the responsible researchers, explaining the relevant aspects and any doubts that may arise in this regard. The document must be signed by each recruited patient if she wishes to participate voluntarily. Additionally, your vital signs will be assessed to ensure your safety when taking measurements and baseline data will be generated. The self‐application of the voiding chart will be explained to them, which should be done once a week throughout the treatment. A postural evaluation through a stability test will be performed on all patients using a portable device placed through a harness. The cell phone has inertial sensors and will record position signals. This measurement will be carried out in two instances: pre‐intervention and post‐intervention to obtain postural parameters of anticipatory adjustments, reactive strategies, sensory orientation and dynamic gait. Subsequently, the total sample will be randomly subdivided into two groups consisting of 5 patients. The first group will be treated through the use of oral antimuscarinics for 4 weeks under strict medical indication, with a treatment scheme consisting of 10 mg oxybutynin tablet once a day, while the other 5 remaining subjects will receive a combined oral treatment using the use of oral antimuscarinic under the same scheme (10 mg oxybutynin tablet once a day), but they will also be complemented with boldo powder for 4 weeks under strict medical indication. This last group will be complemented with 1 capsules of 380 mg every 8 hours of boldo (take suggested by the manufacturer), for 5 days in a row and 5 days off. Patients will be monitored weekly by telephone and asked to report the results of the self‐administered voiding record while the bladder control questionnaire for overactive bladder symptoms is administered.

Nct (2023). "Effectiveness of PEA Compared to Placebo on Acute Menstrual Pain." ClinicalTrails.gov.
	This is a double blind, randomised, placebo‐controlled trial to evaluate orally‐dosed Palmitoylethanolamide (PEA) compared to placebo on menstrual pain in otherwise healthy participants 18 years and over.

Nct (2023). "The Effectiveness of the Letrozole-induced Endometrial Preparation Protocol in Frozen-thawed Embryo Transfer (FET)." ClinicalTrails.gov.
	The goal of this single center, non‐blinded, randomized controlled clinical trial to comparison of pregnancy outcomes and perinatal outcomes in patients undergoing IVF treatment (including ICSI) with FET with letrozole‐induce endothelial preparation protocol versus natural cycles, hormone replacement protocol. The main questions it aims to answer are: ‐ To investigate whether letrozole‐induce endothelial preparation is effective in improving the live birth rate and clinical pregnancy rate. ‐ To explore its possible impact on clinically important indicators such as spontaneous abortion rate, implantation cycle cancellation rate, days of endothelial preparation, and number of visits to the clinic. The study subjects were randomized into groups starting at D1‐D3 of the menstrual cycle. The study subjects were stratified according to whether their menstrual cycles were regular or not, and were divided into the following endothelial preparation regimens according to the pre‐prepared stratified zoned randomized group numbers: (1) regular menstrual cycles (25‐35 d): letrozole ovulation‐promoting cycles, natural cycles, and hormone‐replacement cycles; and (2) irregular menstrual cycles (<25 d or >35 d): letrozole ovulation‐promoting cycles, hormone‐replacement cycle.

Nct (2023). "Effects of Aerobic Exercises and Yoga on Premenstrual Syndrome." ClinicalTrails.gov.
	There are many different signs and symptoms of premenstrual syndrome (PMS), including mood swings, sensitive breasts, food cravings, exhaustion, irritability, pain and sadness. Premenstrual syndrome is thought to have affected up to 3 out of every 4 women who are menstruation. A consistent pattern of recurrence exists for symptoms. However, the physical and emotional changes you go through with premenstrual syndrome can range from hardly perceptible to severe. Some people's physical discomfort and emotional stress are so severe that it interferes with their daily life. Regardless of the severity of the symptoms, most women's signs and symptoms go away four days following the start of their menstrual cycle. Various treatment options are available in the literature to effectively manage these issues through Pharmacotherapies. All these interventions are reported to have beneficial effect for these problems. In this study the effects of aerobic exercises and Yoga on premenstrual syndrome population will be analyzed. This study will be a randomized clinical trial which will incorporate two different interventions. Aerobic exercises and yoga would be administered to the females. 32 patients will randomly divided into two groups. Assessment will be done by using PMS scale and visual analogue scale. The goal of this study to compare the effects of aerobic exercises and yoga on premenstrual syndrome. Subjects meeting the predetermined inclusion criteria will be divided into two groups. 1stgroup will be treated with aerobic exercise. 2nd group will be treated with yoga movements. The pain intensity (Visual Analog Scale) and PMS Scale will be measured before, at the end of 15 days, and after 1 month of treatment program. Recorded values will be analyzed for any change using SPSS25.

Nct (2023). "Effects of Antioxidant Supplementation of Culture Media on IVF Embryos." ClinicalTrails.gov.
	This study is focused on the role of antioxidants (AOXs) in mitigating reactive oxygen species and oxidative stress, which have been associated with failure in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The research aimed to evaluate the effect of two different methods of antioxidants supplementation at two O2 tensions on blastocyst utilization and expansion rates. To achieve this, 3603 zygotes from infertile couples undergoing IVF or ICSI were included in the study. The zygotes were divided into two groups: Group 1A and 1B: Antioxidants every 12 hours at either 5% or 20% O2 tension, respectively. Group 2A and 2B: Antioxidants only once at the beginning of embryo culture at either 5% or 20% O2 tension, respectively. .

Nct (2023). "Effects of Aromatherapy Massage in Menopausal Women With Knee Osteoarthritis." ClinicalTrails.gov.
	The aim of this study is to investigate the effect of aromatherapy massage performed with bergamot oil for 4 weeks on pain, function, sleep and menopausal symptoms in menopausal women with knee osteoarthritis. Participants will be randomly divided into 3 groups as Bergamot, placebo and control. In addition to the conventional treatment, the Bergamot group will receive 2 sessions of Bergamot oil per week for 4 weeks, and the placebo group will be massaged with 2 sessions of sweet almond oil for 4 weeks. the control group will continue conventional treatment for 4 weeks. All assessments will be performed before starting treatment and at the end of 4 weeks of treatment. Participants' pain will be evaluated by VAS, Functions by WOMAC, Sleep quality by PSQI, menopausal symptoms by Menopause Symptoms Evaluation scale. At the end of the study, the satisfaction of the participants will be evaluated with VAS.

Nct (2023). "Effects of Breathing Exercises in Women With Chronic Pelvic Pain." ClinicalTrails.gov.
	The primary cause of the complex interaction of chronic pelvic pain originates from the visceral organs in the pelvic cavity, and it has been observed that musculoskeletal dysfunctions (such as increased muscle activity in the pelvic floor muscles) are often accompanied by visceral painful stimuli in the pelvic region as a result of shared innervation and visceral‐somatic convergence. This study aims to investigate the effect of breathing exercises combined with pelvic floor exercises on pain, pelvic floor muscle activity, psychological factors, and quality of life in women with chronic pelvic pain.

Nct (2023). "Effects of Core Stability Exercises in Postpartum Female With Lumbopelvic Pain." ClinicalTrails.gov.
	Lumbopelvic pain refers to self‐reported pain in the lower back, sacroiliac joints, or a combination of these locations, among pregnant and postnatal women. Approximately 50% of pregnant women report lumbopelvic pain to some degree. Recent studies indicate the importance of hip extensors, pelvic floor muscle (PFM) and transverse abdominal muscle (TrAM) in the development of lumbopelvic pain.Moreover, pelvic instability, asymmetry and insufficient compression of the sacroiliac joints contribute to continuous lumbopelvic pain after delivery. In Europe every tenth women shortly postpartum and every sixth has reported similar symptoms 6 weeks later. Age, PGP during pregnancy and abdominal midline doming were associated with experiencing PGP shortly postpartum. Studies have demonstrated the importance of choosing an optimal treatment strategy in clinical practice, and 5 subgroups of self‐rated pain locations have been identified in the pelvic area. The study focused on pelvic girdle pain (PGP), or PGP in combination with lumbar pain, since these groups have been shown to have the highest impact on activity levels and health‐related quality of life. Stabilization exercises that include dynamically controlling the lumbar segments and pelvic joints have been shown to result in functional improvement in patients with lumbopelvic pain. The term "core stability" is commonly used to refer to the ability of these "core" muscles to stabilize the lumbar spine and pelvic girdle during static postures and dynamic movements. A host of theories and "stabilization exercise" programs have been developed to train these muscles as a means of treating and/or preventing lower back pain (LBP). However, there is still much inconsistency and debate both in the clinical and research communities with regards to what constitutes "core stability" and a "stabilization exercise". Chronic pain is a global healthcare burden with as much as of 11% of the US population suffering from pain lasting six months or longer, and upwards of 20% in Europe. Chronic pain can lead to depression, anxiety, sleep disturbances, and impairment in cognitive tasks. Established research supports VR(virtual relaity) as a treatment strategy for burn pain, acute pain, and experimentally induced pain. Two primary approaches afford analgesic benefits of VR: distraction therapy and immersive‐ness. Distraction therapy temporarily takes attention away from pain while patients are engaged in the VR experience. In immersive VR, the user can interact with an artificial environment to treat chronic pain. In immersive VR, the user can interact with an artificial environment to treat chronic pain. One form of immersive VR is virtual embodiment. Virtual embodiment refers to the sense of owning a virtual body, from a first‐person perspective, feeling the agent of the sensory feedback related to the actions of the virtual body. Through activation of somatosensory and premotor circuitry associated with the body parts that are embodied, the use of virtual embodiment as an immersive VR technique has been shown to influence pain‐free range of motion in patients with unilateral chronic shoulder pain. A case series was conducted in 2020, in which they describe two case studies that use embodiment in virtual reality as a treatment for chronic low back pain. The purpose of this case series was to determine the feasibility of a novel virtual reality‐based digital therapeutic for the treatment of chronic pain. Two patients with chronic low back pain received seven sessions, two sessions per week, of a novel digital therapeutic that combines virtual embodiment with graded motor imagery to deliver functional rehabilitation exercises using an off‐the‐shelf virtual reality system. Pain catastrophizing scale was assessed before the first session and after the seventh session to determine the extent to which virtual embodiment training can improve psychological symptoms of chronic low back pain. In both patients, pain intensity was improved after individual sessions of virtual embodime training. They concluded that embodiment in virtual reality improves symptoms of persistent chronic low back pain. A study (RCT) was conducted in 2022 and their study have measured the Effects of a motor control exercise program on lumbopelvic pain recurrences and intensity in pregnant women with a history of lumbopelvic pain. Forty pregnant women with a history of lower back pelvic pain (LBPP) were recruited and randomly allocated to a control (20 participants) or intervention (20 participants) group. The control group have received standard prenatal care, including basic information on what to do when suffering from LBPP. The intervention group have participated in three 40‐min exercise sessions per week from < 20 weeks until 34‐36 weeks of gestation: one supervised group session via the Zoom platform (once a month) and two unsupervised sessions at home. A motor control exercise program was developed to target strengthening of the lumbo‐pelvic‐hip core muscles and to improve spinal and pelvic stabilization. Participants of this group have also received standard prenatal care. They concluded that motor control exercise program have allowed pregnant women to progress at their own pace through different levels of exercises. In addition, the use of technology in the follow‐up of the women will make the approach flexible and adapted to their daily routines. The purpose of the study is to reduce the potential abuse, dependency of painkillers and manual therapy intervention for treating chronic lumbopelvic pain. In order to promote an advance and noninvasive method for treating lumbopelvic pain in postpartum female this study will help to design better rehabilitative program including core stability exercise using the analgesic and distracting effects of Immersive Virtual reality. This study will help physiotherapist as well as other health care professionals to treat other factors contributing to lumbopelvic pain other than weak muscles and posture alignment in postpartum female through virtual reality.

Nct (2023). "Effects of Functional Versus Core Stability Exercises on Pain and Sleep Quality in Patients With Primary Dysmenorrhea." ClinicalTrails.gov.
	To compare the effects of Functional and Core stability exercises on pain and sleep quality in Patients with Primary Dysmenorrhea and to check the results of exercises may be effective in pain during Menstrual and before cramping in menses.

Nct (2023). "Effects of Hypopressive Abdominal Gymnastics in Urinary Incontinence." ClinicalTrails.gov.
	Society is facing a longer life expectancy due to improvements in medicine, which leads to an increase in the aging population. According to the National Institute of Statistics (INE), the population over 65 years of age has been increasing from 2001 to 2020, assuming a growth of 14.6% in Europe and 13.6% in Spain. Demographic indicators indicate a greater increase in life expectancy in women (from 82.7‐85.1 years) than in men (75.9‐79.6 years). Currently, women present more specific health problems than men due to their physiological conditions, such as the menopausal transition. At the vasomotor level, hot flashes or hot flashes form the most distinctive element of this stage at the sexual level, such as the lack of lubrication, discomfort or pain, and altered function; on a psychological level, anxiety and depression, which is a syndrome linked to disorders such as sadness and its impact on menopause, is quite significant; and the affectation of sleep that are one of the main complaints of women at this stage. All these symptoms affect the quality of life of women both physically and mentally. With aging and the incidence of menopause, a series of changes in women's health take place, constituting a natural and inevitable process; which can cause unwanted events, such as urinary incontinence. UI is defined as the involuntary loss of urine, within urinary incontinence the most prevalent is stress urinary incontinence (SUI) in 10‐30% in most studies, and compared to men 75% of women are more affected than men. This condition can cause disorders in the quality of life, and among the main risk factors are increasing age, parity, family history of prolapse, obesity, lifting heavy objects and constipation also influences. Women with prolapses may present with vaginal, bladder, bowel, back, abdominal, and sexual symptoms. Women frequently suffer from UI due to atrophic changes in the urogenital tract. Therefore, a conservative treatment where the evaluation of the pelvic floor strength and the functional use of pelvic floor muscle training are previously carried out is recommended to achieve health benefits and therefore quality of life. Recent studies have shown that women with pelvic floor dysfunctions who perform pelvic floor muscle training through hypopressive abdominal exercises improve the pelvic muscles and quality of life of postmenopausal women with UI and prolapses. The hypopressive abdominal exercises (AHT) technique can be classified as a breathing exercise. It was developed by Dr. Marcel Caufriez, a physical therapist in 1980. This inventor theorized that the decrease in abdominal pressure obtained with AHT may produce reflex activation of the abdominal wall and pelvic floor muscles, thus reducing UI and prolapses. The AHT, in summary, involves diaphragmatic breathing, total air breathing, and gradual contraction of the transverse abdominis and intercostal muscles with rise in the diaphragm and apnea. This conservative treatment technique is adaptable to the mind (since you have to concentrate on breathing) and body integration exercise that can be worked on anywhere and anytime, without the need for special equipment. The directors of this doctoral thesis have experience in this field, with several works published in journals located in the first tercile and quartile of their categories according to the JCR index.

Nct (2023). "Effects of Kegel Exercises With and Without Myofascial Release in Chronic Pelvic Pain." ClinicalTrails.gov.
	Chronic pelvic pain (CPP), defined as a noncyclical pain lasting for more than 6 months can lead to lower physical performance and quality of life in women. In this study the effects of Kegel Exercise with and without myofascial release in chronic pelvic pain population will be analyzed. This study will be a randomized clinical trial. Kegel Exercise and Myofasical Release would be administered to the chronic Pelvic pain Females. Subjects meeting the predetermined inclusion criteria will be divided into two groups. Assessment will be done using Numeric Pain rating scale (NPR), Pelvic floor Impact Questionnaire (PFIQ) and Functional pelvic pain scale (FPPS). Subjects in one group will be treated with kegel exercise with myofascial release, and the other will be treated with kegel exercise only. Each subject will receive a total 12 treatment sessions, with 04 treatment sessions per week. Measurements will be recorded at start and end of treatment session. Recorded values will be analyzed for any change using SPSS.

Nct (2023). "Effects of Kinesio Tape in Primary Dysmenorrhea." ClinicalTrails.gov.
	The opinion of a biostatistician was taken to determine the population of volunteers in the study. As a result of this opinion, 1st year female students who enroll in Toros University Vocational School of Health Services in the 2023‐2024 Fall Semester will form the universe of the research. The sample of the study consisted of 56 volunteers who were 18 years of age and older, who met the inclusion criteria, had a Visual Analog Scale (VAS) score of four and above, a Menstruation Symptom Scale score of 60 and above, and had primary dysmenorrhea (Kinesio tape applied: 28 students, sham The band applied: 28 students will be formed After the female students to be included in the sample are determined, their assignments to the study and control groups will be made according to the randomization method. The research will start in the fall semester of the 2023‐2024 academic year and the data collection period is planned as 4 months (25.09.2023‐25.01.2024). Before starting the application to the students in the study group, the researcher Y.S. Fast and easy application steps will be explained with the demonstration method, supported by visual presentations. Kinesio Taping will be applied to the study group participants during three menstrual cycles. Kinesio taping will be done face to face by the researcher in the laboratory. The participants were given the "Mcgill Pain Scale Short Form", "Menstruation Symptom Scale", "Perceived Stress Scale", "Pittsburgh Sleep Quality Index" and "World Health Organization Quality of Life Scale‐Short Form" immediately after the third cycle and the fourth cycle without treatment. ‐BREF‐TR)" will be applied. The follow‐up of the implementation process will be recorded with the MSF and KBIF prepared by the researcher. Sham taping (fake or tensionless kinesio taping) will be applied to students in the placebo group. The quality of the kinesio tape used in sham taping will be the same. "Mcgill Pain Scale Short Form", "Menstruation Symptom Scale", "Perceived Stress Scale", "Pittsburgh Sleep Quality Index" and "World Health Organization Quality of Life Scale‐Short Form (WHOQOL‐BREF‐TR) administered to participants in the placebo group before the first session )" will be refilled at the end of the third cycle and at the end of the fourth cycle without treatment. In order to eliminate the ethical problems that may occur in the control group, kinesio taping will be applied to the participants in this group after the data collection process of the research is completed.

Nct (2023). "EFFECTS OF LASER PUNCTURE VERSUS ULTRAVIOLET ON POLYCYSTIC OVARIAN WOMEN." ClinicalTrails.gov.
	Obese women with polycystic ovarian syndrome aged between 25 and 35 years old will be divided into three groups. For three months, group (A) will receive laser puncture (3 sessions per week), along with a metformin supplementation, group (B) will receive ultraviolet radiation (3 sessions per week), along with a metformin supplementation, while group (C) will receive only metformin supplementation. The follicular size will be measured using ultrasound, while, female sex hormones, and serum 25‐hydroxyvitamin D levels will bel evaluated using blood analysis

Nct (2023). "Effects of Myofascial Release and Electrical Stimulation in Chronic Pelvic Pain." ClinicalTrails.gov.
	Myofascial pelvic pain (MFPP) caused by myofascial trigger points (MTrPs) is a major contributor to chronic pelvic pain in women. In females, pelvic pain ''is the single most common indication for referral to women's health services. Pelvic floor physical therapy with myofascial release improve mobility, and reduce pain by releasing the painful trigger points following restrictions in connective tissues that are related to pelvic floor.In this project we will observe effects of myofascial release with and without electrical stimulation on pain and functionality in women with chronic pelvic pain.It has been hypothesized that myofascial release along with electrical stimulation help in reducing pain and improve functionality in women.Patients will be having sessions for consecutive 4 weeks and will be exposed to both types of techniques to find out the effective results. The study will be randomized control trial.For pain numerical pain scale (NPS),functional pelvic pain scale(FPPS) and pelvic floor impact questionnaire‐7 will be used to asses pain and functionality respectively. A randomized control trial will be conducted on two groups. Group 1 will receive myofascial release with electrical stimulation in women with chronic pelvic pain for 4 weeks with 50‐280 Hz frequency and a pulse duration of 50 µs for 10 minutes along with 10 minutes myofascial release..On the other hand Group 2 will receive myofascial release without electrical stimulation on pain and functionality in women with chronic pelvic pain. In previous studies there is ample amount of research conducted on chronic pelvic pain but there were very few recent studies available on myofascial release,so this relation of use of myofascial release with and without electrical stimulation on pain and functionality in chronic pelvic pain should also be carried out.

Nct (2023). "Effects of Myofascial Release With and Without Thiele Massage." ClinicalTrails.gov.
	Dyspareunia is characterised by recurring or chronic discomfort during sexual intercourse that causes distress. Dyspareunia can be superficial, causing pain when vaginal insertion is tried, or profound. Women who experience sexual pain are more likely to experience sexual dysfunction, relationship distress, decreased quality of life, anxiety, and depression. One in five nulliparous women (a female who has never given birth to a baby) experiences moderate dyspareunia. Myofascial pain is typically treated using manual manipulation (Manual manipulation involves using skilled, hands‐on maneuvers to perform soft tissue mobilization, myofascial release and more) or Thiele massage. In this study the aim is to find the individual and combined effect of these techniques. The study will be Randomized Controlled Trial (RCT). Non probabiity convenient sampling technique will be used to assign randomly half of patients in group A for the experimental group and half in group B who will meet the inclusion criteria. Group A will include participants who will receive myofascial releases and Thiele massage. Whereas Group B will include participants who will receive myofascial releasing techniques but not Thiele massage. Both group will have 1 session per week for 12 weeks. Numeric pain rating scale, Female sexual function index, Functional pelvic pain scale would be used as an outcome measure tools. The collected data will be analyzed in Statistical Package for the Social Sciences (SPSS) 25

Nct (2023). "Effects of Pelvic Floor Exercise Training in Postmenopausal Genitourinary Syndrome." ClinicalTrails.gov.
	Genitourinary syndrome of menopause (MGS) is a clinical picture accompanied by genital and urinary symptoms and is commonly seen in the postmenopausal period. In the literature, the effects of drug and non‐drug methods in the improvement of these symptoms have been investigated in many different designs. There is limited evidence that pelvic floor physiotherapy improves vulvovaginal blood flow with repetitive muscle activation, reduces vulvar irritation with reduction in urinary incontinence episodes, and normalizes pelvic floor muscle tone in the treatment of MGS. In addition, there is no study to the best of our knowledge investigating the effects of pelvic floor muscle exercise training and patient/individual training, in which individuals are informed. Therefore, the aim of this study is to compare the effects of pelvic floor muscle training and patient/individual information training in the presence of a physiotherapist on genitourinary symptoms and quality of life in individuals with GSM and to contribute to science in the light of this information. Before starting the study, the physical (height, body weight) and sociodemographic characteristics (age, marital status, educational status, employment status), medical history and menopausal characteristics of the individuals will be recorded. In addition, the pelvic floor muscle strength of the individuals will be evaluated at the beginning of the study and after the study is completed; genital symptoms, urinary symptoms and quality of life and scales will be questioned. Within the scope of individual/patient information education, menopause and menopause‐related complaints, genitourinary (genital, sexual and urinary‐related) symptoms of menopause, sexual function, the effect of menopause on sexual functions, recommendations for menopausal symptoms and complaints, and the structure and function of the pelvic floor muscles and pelvic floor muscles. Information will be given including recommendations for base health. This training will be given at the beginning of the study and will be repeated after 4 weeks to increase the benefit of the training. Individuals will be included in the progressive exercise training program within the scope of the pelvic floor muscle exercise training program. In the controls to be made every 15 days, the exercise compliance of the individuals will be monitored and the number of exercises will be increased. Exercise charts will be given in order to increase the adaptation of individuals to exercise and the benefit they will gain from exercise. The estimated time in this study is 8 weeks and it is planned to include 50 volunteers in the study.

Nct (2023). "Effects of Physical and Psychosocial Stress on Functional Hypothalamic Amenorrhea in Exercising Women." ClinicalTrails.gov.
	The goal of this clinical trial is to determine how changes in exercise and psychosocial stress may influence the risk of menstrual cycle irregularities in female runners and cyclists. The main questions it aims to answer are: ‐ Does the implementation of exercise or psychosocial stress effect circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length? ‐ Is there an additive effect of combined exercise and psychosocial on circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length? Participants will be asked to do the following over the 3 month enrollment period: ‐ attend a laboratory visit at the beginning and end of the study to have their resting metabolic rate, aerobic fitness, and body composition tested ‐ monitor their menstrual cycle length, daily perceived stress levels, physical activity, and diet each month ‐ provide several urine and saliva samples each month ‐ either maintain their usual physical activity and lifestyle habits (control group), increase the duration of their weekly running or cycling mileage by 30% (exercise stress group), complete cognitive function tasks designed to be stressful (psychosocial stress group), or increase the duration of their weekly running or cycling mileage by 30% and complete cognitive function tasks designed to be stressful (exercise + psychosocial stress group) during the final month of enrollment. Researchers will compare control, exercise stress, psychosocial stress, and exercise + psychosocial stress groups to see if there is an effect on circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length.

Nct (2023). "Effects of Therapeutic Tapping in Primary Dysmenorrhea." ClinicalTrails.gov.
	Literature suggested that kinesio tape technique, one of the effective physiotherapy technique, used for Primary dysmenorrhea, to stimulate muscle movements, assist weak muscles (fascia and soft tissue), reduce discomfort and muscle cramps, facilitate proprioceptive input, boost lymph and blood flow, and relieve pain. This will be a randomized controlled trial, with three groups. Participants in the experimental group will receive therapeutic tape on the sacral and suprapubic regions with the Star shape and ligament with general physical therapy session. Sham group (ST) group will receive sham taping with general physical therapy session. Participants in Control group (CG) will receive only general physical therapy session. All groups will be assessed at baseline, at 8th week and 12th week for clinical symptoms, QOL and academic performance.

Nct (2023). "Efficacy and Safety of High Dose Vitamin D Supplementation for Overactive Bladder Dry in Children." ClinicalTrails.gov.
	Overactive bladder(OAB), characterized as urinary urgency accompanied in many instances by frequency and sometimes nocturia, with or without urinary incontinence, in the absence of urinary tract infection or other documented pathology, is a common clinical entity in pediatric urology. The majority of patients with OAB do not experience incontinence yet suffer from symptoms of urgency, frequency, and nocturia, which has been termed OAB dry. Currently, standard urotherapy is proposed as the first‐line therapeutic options and adjunctive anticholinergics are usually used when urotherapy alone failed. Behavioral therapy often fail to achieve satisfied symptom control as children's poor compliance. In addition,adverse side effects such as dry mouth, constipation, gastro‐oesophageal reflux result in early pharmacologic treatment discontinuation. It was informed that patients with OAB are more likely to suffer from vitamin D deficiency. The aim of the study is to determine the effect of vitamin D supplementation as an adjunctive therapy to behavioral therapy in the treatment of OAB dry. Eligible patients aged 5‐18 years with a diagnosis of OAB dry will be randomly assigned into three groups to receive high dose vitamin D supplementation (combined with standard urotherapy ) , solifenacin (combined with standard urotherapy ) or standard urotherapy alone. Serum levels of 25(OH)D will be measured at baseline. Symptoms severity will be assessed at baseline and followup. All the other sociodemographic data will be also assessed. The study will give more information on the application of vitamin D supplementation in the management of OAB dry.

Nct (2023). "Efficacy and Safety of VB10.16 Alone or in Combination With Atezolizumab in Patients With Advanced Cervical Cancer." ClinicalTrails.gov.
	This is a two‐arm randomized, double‐blind, placebo‐controlled phase 2 selection trial to evaluate the efficacy and safety of VB10.16 alone or in combination with atezolizumab in patients with HPV16‐positive, PD‐L1‐positive, recurrent or metastatic cervical cancer who are refractory to pembrolizumab with chemotherapy with/without bevacizumab. A selection design with a margin of practical equivalence will be implemented to monitor efficacy of the two experimental arms (VB10.16 + atezolizumab vs. VB10.16 + placebo). The trial consist of 2 parts: the first part which investigates VB10.16 + placebo versus VB10.16 + atezolizumab. Approximately 30 patients will be included in each group. The goal of this part is to evaluate which of the two treatments is the superior. The second part of the study will select the superior treatment from part 1 and investigate the safety and efficacy of additional 70 patients.

Nct (2023). "Efficacy and Safety Study of First-line Treatment With SG001 Plus Chemotherapy ± Bevacizumab Versus Placebo Plus Chemotherapy ±Bevacizumab for Recurrent, or Metastatic Cervical Cancer With PD-L1 Positive (CPS≥1)." ClinicalTrails.gov.
	The purpose of this study is to assess the efficacy and safety of SG001 plus one of four platinum‐based chemotherapy regimens compared to the placebo plus one of four platinum‐based chemotherapy regimens in the treatment of adult PD‐L1 positive (CPS≥1) women with recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The study include two stages: the safety run‐in phase and phase Ⅲ trail. Upon completion of the first stage study, the Safety Monitoring Committee (SMC) will decide whether to proceed directly to Phase Ⅲ study. The primary study hypotheses are that the combination of SG001 plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression‐free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 2) Overall Survival (OS).

Nct (2023). "Efficacy of Chemotherapy Alone in Patients With Poor-differentiated Early-stage Cervical Cancer." ClinicalTrails.gov.
	This study is aimed to enroll patients with early‐stage cervical cancer (FIGO 2018 IB1‐IB2) who undergo radical hysterectomy and the postoperative pathology doesn't meet Sedlis criteria or the "four‐factor" model but with poorly differentiated squamous/adenocarcinoma/adenosquamous carcinoma. Patients will be randomly divided into two groups in a 1:1 ratio. The experimental group received 4 courses of paclitaxel and cisplatin (once every 3 weeks) for adjuvant chemotherapy within 4 weeks after surgery, while the control group don't not receive any adjuvant therapy but only received regular follow‐up. The disease status of all patients will be evaluated within 4 weeks after the end of all treatment and every 12 weeks thereafter, including gynecological examination, laboratory indicators, imaging evaluation, and the prognosis of the two groups will be compared.

Nct (2023). "Efficacy of Combined Pharmacotherapy Versus Solifenacin With Vaginal Estrogen Cream for Women With Detrusor Overactivity." ClinicalTrails.gov.
	Women with detrusor overactivity who were refractory to anti‐muscarinics were enrolled for prospective study. Patients were divided into two groups: one receive combined pharmacotherapy with solifenacin and mirabegron, and the other received solifenacin and vaginal estrogen cream. Incontinence‐related symptoms distress and impact on quality of life were evaluated by short form of Urinary Distress Inventory, (UDI‐6), Incontinence Impact Questionnaire (IIQ‐7) and Overactive Bladder Symptom Score (OABSS). Objective outcomes include changes from baseline in episodes of daily micturition, urgency, urinary incontinence and nocturia.

Nct (2023). "Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	This study will comprise of two groups (A and B) with 71 participants in each group carried for a duration of 24 weeks. Intervention Details for Group A (Duration 1‐12 weeks): Participants will be given Vitamin D (VD) supplementation at a dose of 600,000 IU along with Calcium 1000 mg/day. Mid‐Point (At 12 weeks): Patients will have a consultation for clinical interpretation. They will undergo biochemical assessment, including the estimation of Insulin Resistance, Free Androgen Index, and Total Antioxidant Capacity. After 12 weeks They will receive standard treatment for Polycystic Ovary Syndrome (PCOS), which includes Glucophage XR 750 mg once at dinner for 15 days, then twice daily. Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off and Calcium 1000 mg/day Intervention Details for Group B (Duration 1‐12 weeks): Participants in Group B will receive standard PCOS treatment mentioned earlier: Glucophage XR 750 mg once at dinner for 15 days, then twice daily. Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off. Additionally, they receive Calcium 1000 mg/day. Mid‐Point (At 12 weeks): Patients will have a consultation for clinical interpretation. They will undergo biochemical assessment, including the estimation of Insulin Resistance, Free Androgen Index, and Total Antioxidant Capacity. Intervention Details for Group A (After 12 weeks) They will receive VD supplementation (600,000 IU) during this time and continue to receive Calcium 1000 mg/day. Calculations of HOMA‐IR and Free Androgen Index will be done at 12 and 24 weeks and the results will be compared. {HOMA‐IR: HOMA‐ IR index, a commonly used marker of IR, will be calculated using the formula: HOMA‐IR = fasting glucose levels [mmol/L] × fasting insulin levels [μU/mL]/22.5 Free Androgen Index will be derived from TT and SHBG, normally measured in nanomoles per liter. FAI =100 (TT /SHBG)}

Nct (2023). "Efficacy of Oocyte Activation With Two Types of Ca2+ Ionophore." ClinicalTrails.gov.
	Background: Oocyte non‐activation (OAD) is the main cause of fertilization failure in intracytoplasmic sperm injection (ICSI) cycles. Oocyte activation involves a series of consecutive events that take place in the oocyte during fertilization, triggered by the action of sperm‐specific phospholipase C zeta (PLCz) that causes an increase in the amount of free Ca2+. This increase, as well as its transient elevations in space and time, is species‐specific. Defects in this pattern of Ca2+ release and oscillation are attributed to most cases of OAD. Several strategies have been described and applied to achieve artificial oocyte activation (AOA), which use mechanical, electrical, or chemical stimuli, among which the use of calcium ionophores such as ionomycin and A23187 (calcimycin) predominates. Documented fertilization and pregnancy rates appear to be improved in patients with previous low fertilization rates or total fertilization failures after using ICSI‐AOA compared to conventional ICSI. However, the lack of well‐designed studies, the heterogeneity of the population undergoing AOA, and the scarcity of results comparing different AOA protocols make it difficult to assess the clinical efficacy and safety of the technique. Study question: In patients with prior fertilization failure or low fertilization rates (30% or less), does AOA improve reproductive outcomes compared to conventional ICSI in patients with prior fertilization failure? and if it does, which protocol is more efficient?

Nct (2023). "Efficacy of Plasmid Elenagen in Combination With Gemcitabine in Patients With Platinum-resistant Ovarian Cancer." ClinicalTrails.gov.
	The purpose of this clinical study is to evaluate safety and efficacy of ELENAGEN, a novel anticancer therapeutics (plasmid DNA encoding p62/SQSTM1) protein, as an adjuvant to chemotherapy with Gemcitabin (GEM) in patients with advanced platinum‐resistant ovarian cancer. This is a prospective randomized multi‐center study with two arms. Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks) is administered in both arms: In the Chemo arm (n = 20) Gemcitabine is the only treatment, and in the ELENAGEN arm (n = 20) GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint is progression‐free survival (PFS), and the secondary endpoint is safety.

Nct (2023). "Elastographic Improvement of Vaginal Atrophy Treated by Erbium Yag Laser." ClinicalTrails.gov.
	In the postmenopausal period, especially due to estrogen deficiency, vaginal atrophy occurs in the vulvo‐vagina, lower urinary tract, pelvic floor muscles and endopelvic fascia. Vaginal dryness secondary to atrophy in genital organs, pain and tenderness especially during sexual intercourse, and decreased genital elasticity are the most common symptoms and signs during the postmenopausal period. With regard to the urinary system, frequent urination, feeling of urgency, recurrent urinary tract infections, organ prolapses‐urethrocele, cystocele, urethral prolapse and stress or urge type urinary incontinence could be seen.These signs and symptoms were recognized in 2014 by the International Society for the Study of Women's Sexual Health (ISSWSH) and the North American Menopause Society (NAMS) under the main title OF "genito‐urinary syndrome of menopause" (GSM). During the postmenopausal period, a detailed history should be taken, a complete physical examination should be performed, and various tests should be performed for the evaluation of GSM. Laser is a treatment option for the genitourinary symptoms that could occur at the postmenopausal period. Laser can be applied to vulva by giving an external beam, or it can be applied intravaginally or directly to the urethra using vaginal and urethral cannula. The smooth mode application of the Er:YAG laser ensures that the laser beam retains the heat it gives without ablation and penetrates deeper into the tissue. After laser application, thermomechanical and thermochemical effects occur in the tissue, respectively. It provides controlled thermal energy and causes shrinkage of the collagen fibrils in the vaginal epithelium and lamina propria. It also induces neocollagenesis, elastogenesis and neoangiogenesis by temperature change. With minimum damage to the peripheral tissue, the viable cells in the target tissue reacts to this temperature change by expressing heat shock proteins (HSP). Then, HSP increases the levels of transforming growth factor‐beta, fibroblast growth factor, epidermal growth factor, platelet‐derived growth factor, vascular epithelial growth factor which induce neocollagenesis and neoangiogenesis. Therefore, the thermal energy stored in the vaginal wall induces proliferation of the epithelium which is rich in glycogen, neovascularization and collagen production in the lamina propria. In this study, evaluation and demonstration of the efficacy of Er:YAG laser for the treatment of atrophic vaginitis in postmenopausal women is intended with Maturation Index (MI), vaginal pH measurement, Female Sexual Function Index (FSFI), Vaginal Health Index (VaHI), Visual Analogue Scale (VAS) and ultrasonographic elastography.

Nct (2023). "Electrostimulation and PFMT for Stress Urinary Incontinence." ClinicalTrails.gov.
	The study involved 24 women 20‐49 years old who have complained of stress urinary incontinence for at least 4 weeks, who gave at least one birth vaginally and signed the consent form. Subjects were excluded if they were pregnant, were diagnosed with vaginismus, urinary tract infections, cancer, epilepsy, pelvic organ prolapse greater than stage I, skin diseases, had undergone previous pelvic floor surgeries, had heart stimulator, or metal implant and were unable to contract the PFM. Study participants were randomly divided into two groups: the I group (n=12), in which participants underwent pelvic floor muscle training (PFMT) and the II group (n=12) in which subjects received pelvic floor muscle exercises combined with electrostimulation (PFMES).Participants were evaluated before the interventions and repeated after 4 weeks. Before and after the interventions, women's quality of life (QoL) was assessed according to the International Incontinence Counseling Questionnaire ‐ Short Form. Perineometry with Pelvexiser perineometer was used to measure pelvic floor muscle strength and endurance and vaginal resting pressure. Statistical analysis was performed by IBM SPSS Statistics 26.0 and Microsoft Excel software 365.

Nct (2023). "EON: a Single-arm Phase II Study of Etigilimab (OMP-313M32) in Combination With Checkpoint Inhibition (Nivolumab) in Patients With Platinum-resistant, Recurrent Epithelial Ovarian Cancer." ClinicalTrails.gov.
	Primary Objectives: 1. To estimate the objective response rate of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. 2. To evaluate the toxicity of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. Secondary Objectives: 1. To determine PFS of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. 2. To estimate the disease control rate of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. 3. To investigate molecular and immunological changes associated with the combination of TIGIT and PD‐1 inhibition; specifically to describe changes in T cell populations (including but not limited to CD3, CD8, CD4, FOXP3) and cell proliferation, as well as report changes in the proportion of macrophage phenotypes M1 and M2 (with phenotypic markers potentially including arginase1, CD11b, PDL‐1, and CD206) 4. To determine feasibility of interrogating the gut microbial signatures and dietary patterns in an ovarian cancer cohort. 5. Identify components and determinants of the gut microbiome that could modulate toxicity or provide a signature of excellent or poor response to cancer immunotherapy.

Nct (2023). "ERr 731® Formulation Evaluation." ClinicalTrails.gov.
	Current clinical and commercialization experiences have been with enteric‐coated formulations of ERr 731®. With the demonstrated safety of this formulation and the absence of anthraquinones in the extract, there is interest in launching a micro‐coated, but not enteric‐coated, formulation to broaden the commercial availability of ERr 731® in new markets. It is proposed that a double‐blinded, randomized cross‐over design in a peri‐menopausal/menopausal and preferably symptomatic group of women (target population for commercialization) is best suited to demonstrate equivalent tolerability.

Nct (2023). "Evaluate the Effect of ReSpace™ Hydrogel on Reducing Rectal Radiation Dose in Radiotherapy for Cervical Cancer." ClinicalTrails.gov.
	This phase II prospective, multicenter, randomized, parallel‐controlled, superiority clinical study will select more than three hospitals with national clinical trial institution qualifications as clinical trial centers, plan to recruit 100 subjects, 50 in experimental group and 50 in control. The patients in expermental group will receive brachytherapy after the hydrogel injection while patients in control group will receive brachytherapy without hydrogel. The aim of the study was to evaluate whether the use of ReSpace™ hydrogel results in a reduction of radiation exposure to the anterior rectum, and to assess its safety.

Nct (2023). "Evaluation of Concomitant Chemo-radiotherapy With Cisplatine vs Gemcitabin in Locally Advanced Cervicouterine Cancer." ClinicalTrails.gov.
	This is a phase III clinical trial, open, randomized 1: 1, controlled, noninferiority, in a single hospital center. This study will include 564 patients with the diagnosis of malignant tumors of epithelial origin of the cervix. Patients will be randomized 1: 1, arm "A" (experimental) to receive concomitant chemotherapy based on gemcitabine at 300 mg / m2 weekly and Arm "B" (control) to receive cisplatin 40 mg / m2 weekly, both arms with RT 50.4 Gy in 5 weeks plus 30Gy brachytherapy at the end of the concomitance. These patients will be treated in the gynecology‐oncology service, candidates for chemo‐radiotherapy, it is intended that the recruitment of patients be done in the first 48 months, with a follow‐up of 3 years. It is intended to include 3 patients per month, until the total sample is completed in four years. The study is divided into three phases, the first of QT / RT concomitant with gemcitabine or cisplatin depending on the randomized arm; with an approximate duration of 1.5 months with a weekly visit, the second phase is brachytherapy in both arms which lasts from 2 to 7 days, and finally the follow‐up phase which lasts for 3 years with a visit every 3 months. In each of the visits we will evaluate the safety of the medication; evaluating adverse events, including laboratory abnormalities as well as acute and chronic toxicity, with the classification according to the common toxicity criteria (CTCAE v4.03) and the efficacy will obtain proportions of clinical and imaging response (TC and / or PET‐CT) with the criteria of RECIST v1.1 and / or PERCIST 1.0. Patient numbers to include. This study will include 140 patients. Test drug, dosage, mode of administration: Gemcitabine at 300 mg / m2 weekly intravenous administration. Duration of the study 9 years.

Nct (2023). "Evaluation of Efficacy and Safety of Two New Formulations Compared to Gynomax® XL Ovule." ClinicalTrails.gov.
	This was a national, randomized, 3‐arms, phase III study conducted in 16 centers in Türkiye. It was aimed to evaluate the efficacy and safety of different fixed dose vaginal ovule formulations of fenticonazole + tinidazole + lidocaine (Formulation A and Formulation B) in the treatment of bacterial vaginosis, candidal vulvovaginitis, trichomonal vaginitis and mixed infections with comparison to Gynomax® XL vaginal ovule.

Nct (2023). "An Evaluation of Maintenance Therapy Combination Mirvetuximab Soravtansine and Olaparib." ClinicalTrails.gov.
	The Principal Investigator hypothesizes the combination of MIRV and Olaparib is an effective, and tolerable, maintenance therapy strategy in platinum sensitive recurrent ovarian cancer.

Nct (2023). "Evaluation of Using Dienogest and N-Acetyl Cysteine on the Volume of Uterine Leiomyoma." ClinicalTrails.gov.
	Group A women will receive Dienogest orally 2mg pills daily for 3 months .20 cases Group B women will receive NAC orally at a dose of 600 mg/day for 3 months ,20 cases

Nct (2023). "Evaluation the Efficacy Between Botox Injection and Combination Pharmacotherapy in Patients With Detrusor Overactivity." ClinicalTrails.gov.
	Patients with detrusor overactivity who were refractory to monotherapy with either anti‐muscarinics or β3‐adrenoceptor agonists were enrolled for prospective study. Patient were divided in two groups, intradetrusor onabotulinumtoxinA injection and combined pharmacotherapy with Mirabegron and Solifenacin. Incontinence‐related symptoms distress and impact on quality of life were evaluated by short form of Urinary Distress Inventory, (UDI‐6), Incontinence Impact Questionnaire (IIQ‐7) and Overactive Bladder Symptom Score (OABSS). Objective outcomes include changes from baseline in daily urgency episodes, urinary incontinence episodes, maximum cystometric capacity, maximum detrusor pressure (Pdetmax) at first involuntary detrusor contraction and volume at first involuntary detrusor contraction were measured.

Nct (2023). "Exogenous Ketone Supplementation in Females With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	Polycystic ovary syndrome (PCOS) affects 1 in 5 females of reproductive age. Commonly characterized as a disorder of infertility, PCOS is often accompanied by 3 potent cardiovascular disease (CVD) risk factors: insulin resistance, endothelial dysfunction, and elevated blood pressure. Accordingly, PCOS is associated with the development of CVD, the second leading cause of death in females in Canada. However, effective treatments to improve cardiovascular health in PCOS are lacking. Exogenous ketone monoester (KME) ingestion has been shown to improves outcomes associated with insulin resistance, endothelial function, and blood pressure regulation in healthy individuals and individuals predisposed to CVD. Therefore, oral ketone supplements offer a practical and effective strategy for improving cardiovascular health; however, this treatment has yet to be evaluated in PCOS. Therefore, the overall goal of this project is to employ KME ingestion to improve markers of cardiovascular health in females with PCOS. On two different days, participants will consume either a beverage containing a ketone supplement or a beverage containing a placebo supplement. The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females with PCOS in comparison with female controls of similar age and body mass index. The effects of KME ingestion will be quantified on: 1) glycemic control during an oral glucose tolerance test; 2) endothelial function using the flow‐mediated dilation test; 3) blood pressure and acute blood pressure regulation; and 4) hemodynamic responses to acute exercise.

Nct (2023). "Extracorporeal Magnetic Innervation in Combination With Mirabegron in the Treatment of Overactive Bladder." ClinicalTrails.gov.
	In this study the investigators are studying the impact of extracorporeal electromagnetic stimulation on the treatment of overactive bladder (OAB). For the research, the investigators will gather participants' basic demographic information (age, co‐morbidities, etc.), results of uro‐gynecological examinations (gynecological and transabdominal ultrasound, uroflow, urinalysis) and the results of different questionnaires, which will be filled out by the participants, describing the burden of the investigated disease and the impact on quality of life. The research will last 8 weeks. Before the start of the research, participants will submit a urine sample to rule out a urinary tract infection and determine baseline laboratory parameters in the urine. Participants will then receive 50 mg of mirabegron daily in the form of tablets, which is used to treat OAB according to current treatment guidelines. Twice a week participants will come to the Department of General Gynecology and Gynecological Urology, Clinic of Gynecology and Perinatology, UMC Maribor, where the investigators will additionally perform extracorporeal electromagnetic stimulation for the treatment of OAB. These treatments will last 20 minutes each time. The patients will be divided into 2 groups, namely one group will receive actual electromagnetic stimulation, and the other group will receive placebo stimulation. At the beginning of the research and after 4 and 8 weeks, the investigators will perform a uro‐gynecological examination, with ultrasound measurements of the remaining urine in the bladder and determination of the thickness of the bladder wall, as well as a uroflow examination. It will be necessary for the participants to submit urine for laboratory tests and to fill out questionnaires regarding OAB symptoms. Based on the safety profile of mirabegron and extracorporeal electromagnetic stimulation, the investigators do not expect any serious side effects. The investigators anticipate that there will be a reduction in the symptoms caused by the overactive bladder. In the event of a serious adverse event, participants can contact the on‐call gynecologist or on‐call urologist at UMC Maribor, who are available 24 hours a day. In the research, the participants' personal data will remain undisclosed, as the investigators will lead each participant under a random number during data processing, and will also display the results in the form of an average for the entire group of participants, so that it will not be possible to draw conclusions about participants' identity based on the results. Participation in the research is voluntary, and participants can stop participating at any stage of the research.

Nct (2023). "Fasting Mimicking Diet (FMD) in Conjunction With Chemotherapy in Advanced Ovarian Cancer." ClinicalTrails.gov.
	Rates of grade 3‐4 toxicity with carboplatin and paclitaxel chemotherapy range 26‐84%. Interventions to reduce toxicity are needed. Short term fasting protects against toxic effects of chemotherapy without decreasing efficacy. In a prospective clinical trial of breast cancer patients randomized to FMD or regular diet during chemotherapy, less antiemetic was required in the FMD group; radiographic and pathologic responses were better in this group. This trial tests whether platinum‐taxane chemotherapy combined with a FMD in advanced and recurrent ovarian, fallopian tube and primary peritoneal cancer patients is associated with decreased toxicity and/ or improved tumor response to therapy.

Nct (2023). "Fluzoparib With or Without Apatinib in Platinum-sensitive Relapsed Ovarian Cancer Previously Treated With PARPi." ClinicalTrails.gov.
	This is a randomized, multicenter, two‐arm, noncomparative, phase II study of fluzoparib with or without apatinib for maintenance therapy in PARPi‐pretreated platinum‐sensitive recurrent ovarian cancer. The primary objective is to evaluate median progression free survival of fluzoparib with or without apatinib.

Nct (2023). "Fremanezumab Treatment of Migraine in Women With Menstrual Migraine Ages 18-45." ClinicalTrails.gov.
	Patients who meet the eligibility criteria and wish to participate will be consented, and will then be randomized to receive two rounds of treatment with either fremanezumab or placebo, administered 3 months apart, to understand efficacy and response in decreasing migraine days. The investigators will monitor with daily logs and use evidenced metrics to assess response. Participants will be carefully screened to ensure that they do not become pregnant while in the study. The investigators will measure monthly hormone levels using salivary samples. Each participant will have three in‐person visits and will have five 5 visits via secure telehealth. The investigators are studying decreased headache days, severity, disability and quality of life.

Nct (2023). "Game Changers for Cervical Cancer Prevention." ClinicalTrails.gov.
	This randomized controlled trial will evaluate Game Changers for Cervical Cancer Prevention (GC‐CCP) for increasing cervical cancer (CC) screening among previously unscreened social network members. The trial will be conducted at 4 study clinics [2 public, 2 private‐not‐for‐profit (PNFP), one each in an urban and rural location]. At each clinic, 40 women screened for CC in the past year will be enrolled in the RCT as index participants (n=160 index) and randomized to the intervention (in two groups of 10) or wait‐list control. The intervention will consist of 7 weekly group sessions that focus on CC stigma reduction, sharing of CC screening experience with others, knowledge of CC facts and myths, and skills building for engagement in CC prevention advocacy with female social network members (alters). Each index will recruit up to three alters (n 440 alters) at baseline who have not screened for CC; these index and alter participants will be followed up at months 6 and 12.

Nct (2023). "Group Preconception Care for Fertility Patients." ClinicalTrails.gov.
	Group Preconception Care for Fertility Patients aims to translate the well‐established group prenatal care model to preconception care to improve pregnancy and neonatal outcomes. In partnership with Pomelo Care (a virtual maternity care program), the investigators are conducting this study using couples at Penn Fertility Care.

Nct (2023). "Home Biofeedback Therapy for Dyssynergic Defecation, Fecal Incontinence and Urinary Incontinence." ClinicalTrails.gov.
	Biofeedback therapy is an effective treatment for the management of patients with constipation and dyssynergic defecation, urinary incontinence, and fecal incontinence, problems that affect 25% of the population in USA. However, it is labor‐intensive, costly, requires multiple office or hospital visits, is not widely available to the vast majority of patients in the community, and is not covered by many insurance companies. It is therefore imperative that a more pragmatic biofeedback treatment program that can be administered at home ought to be developed. Our previous studies have shown that home biofeedback training can be just as useful as office‐based training, both for constipation with dyssynergia and fecal incontinence. These studies were however performed with older technology that included placement of anal probes connected to hand‐held monitors with a liquid crystal display of flashing lights indicating changes in anal pressures. However, these methods are cumbersome and not user‐friendly. Further, there is no commercially available home biofeedback system for dyssynergic defecation. The advent of newer digital technology using cellphone app‐based applications, with real time animations and pictorial displays of anorectal anatomical changes than the traditional liquid crystal display (LCD) lights and computer monitors, if adopted, could immensely improve our ability to provide biofeedback training. Also, the interactive images of the human anatomy that are both dynamic and change in real time during the biofeedback maneuvers can prove to be a significant advance over line tracings showing pressure or electromyogram (EMG) changes that many patients find it difficult to comprehend. These animated real time images could enable the patient to visualize and directly connect with their anal or rectal or pelvic floor muscle dysfunction that is causing their bowel or urinary problem. Also, the use of Bluetooth technology will enable wireless transmission of the pressure changes from inside the body to a cellphone display system, avoiding the hassles of connecting a probe with a hand‐held device, to view changes. Further, the ability to provide voice guided instructions using the cellphone application (APP) will provide a structured treatment program on how to perform biofeedback training at home that mirrors the office biofeedback training. A 3 sensor electronic anorectal probe with a balloon will be placed in the rectum for assessment of anal and rectal pressures, and this will communicate wirelessly with the cellphone app. This new home biofeedback system could significantly improve our current method of performing biofeedback training. Our specific aims are: 1) To test the feasibility, efficacy and safety of a wireless anorectal probe, and a cellphone app‐based and Bluetooth interfaced, voice guided home biofeedback training system. 2) To compare the efficacy and safety of home biofeedback therapy with the standard of care office biofeedback therapy for the treatment of patients with dyssynergic constipation, fecal incontinence, and urinary incontinence; 3) To examine and compare the cost‐effectiveness of home biofeedback therapy with office biofeedback therapy, in each of the 3 patient cohorts. Our overall hypothesis is that Home Biofeedback Therapy (HBT) is non‐inferior to Office‐Biofeedback Therapy (OBT), but is more user friendly, easy to administer, and cost effective for the management of patients with constipation and dyssynergic defecation, fecal incontinence and urinary incontinence.

Nct (2023). "Hot Water Therapy for the Treatment of Menopause-related Hot Flashes." ClinicalTrails.gov.
	Menopause is the time at which menstruation stops and perimenopause is the period before, characterized by a continuous reduction in estrogen and progesterone levels in the blood. Concurrently, the reductions in estrogen leads to a rise in another hormone, orexin. The reduction in circulating estrogen and progesterone and the increase in circulating orexin have been demonstrated to play a major role in menopause‐related hot flashes and night sweats, known as vasomotor symptoms (VMS), as well as other symptoms such as mood disorders. While hormonal replacement therapy remains the most effective defense against VMS, there has been a progressive decline in its prescription due to side effects such as uterine bleeding, increased risk of thromboembolism, as well as increased rates of gallbladder, breast, endometrial, and urinary cancers, highlighting the need for alternative non‐hormonal treatments. Exercise, and specifically the thermoregulatory benefits of exercise (i.e. increased sweating and skin blood flow, as well as reduced core temperature), improves vasomotor symptoms in women going through menopause. Heat acclimation/heat therapy improves thermoregulatory responses by more than twice as much as exercise alone, however, to date, no studies have investigated the effects of heat acclimation on menopause‐related vasomotor symptomology. Accordingly, the purpose of this study will be to examine whether hot water bathing improves vasomotor symptomology, with the guiding hypothesis that hot water bathing will reduce vasomotor symptomology. Recruitment For this study, we will aim to recruit 100 women who have either undergone or who are undergoing menopause and who self‐report experiencing vasomotor symptomology. Study protocol An initial visit will be organized during which the potential participants will complete a health screening and consent to participate in the study. After which, the participants will undergo a two week‐long baseline period during which they will track their vasomotor symptomology using a vasomotor symptomology journaling template, as well as complete a standardized menopause symptomology questionnaire. The participants will be randomized into two groups: a hot water bathing group and a sham group. Following the baseline period, participants will report to the climate chamber located in the Hybl center to have their thermoregulatory responses assessed. This will consist of slowly walking on a motorized treadmill in 99.5°F (37.5°C) and 30% relative humidity conditions, for 30 min after which the humidity in the climate chamber will be progressively increased until an inflection in the participants' core temperature is detected. Before and/or during these trials, core temperature, heart rate, whole‐body sweat losses, thermal comfort, local sweat rate, and skin blood flow will be measured, and a 6 ml ( 1 tsp) blood sample will be taken, to assess heat loss adaptations. Next, the participants will begin their 10‐day, hot water bathing sessions. The participants in the treatment group will be asked to submerge themselves in a bathtub filled with 105°F (40.5°C) water, and to remain at this depth until their esophageal temperature reaches 101.5°F (38.6°C). Based on previous hot water therapy studies using this protocol, this should take approximately 25‐35 min. After attaining the target core temperature, the participants will be given a stool to sit on in order for them to remain at waist depth in the water in order to maintain their core temperature at 101.5°F (38.6°C) for an additional 60 min. Participants in the sham group will be immersed up to the shoulder in a 97°F (36°C) tub for 30 min and then to waist‐level for another 60 min in order to mimic the same hydrostatic pressures as were experienced by the participants in the heat therapy group, but without the heat exposure. Finally, following the heat therapy sessions, the participants will be asked to take hot baths at home once every four days (as this is the frequency needed to stay heat acclimated) for one month, h le continuing to track their vasomotor symptomology. At the completion of this follow up period, they will complete a study exit survey that has questions regarding their experience in the study.

Nct (2023). "Immunonutrition in ERAS Protocols in Gynecologic Oncology." ClinicalTrails.gov.
	Malnutrition has a major effect not only on the postoperative course of cancer surgery but can also complicate or even limit administration or compromise the effectiveness of other treatments such as chemotherapy or radiotherapy in the perioperative period. Immunonutrition is a type of artificial nutrition based on the use of some types of macro‐ or micronutrients.The purpose of this review was to evaluate the use, indications, and effects of these formulas in oncologic surgical patients in real time and to identify the types of patients who can benefit from enteral immunonutrition.

Nct (2023). "The Impact of Preoperative Bowel Exercise on Postoperative Bowel Functions in Gynecologic Malignancies." ClinicalTrails.gov.
	This randomized study was approved by the Tepecik Training and Research Hospital Ethics Committee and conducted between January 1, 2023, and August 31, 2023. Patients diagnosed with gynecologic malignancies at our center were included in the study. Patients in the study group were provided with abdominal exercises one week before surgery, and they practiced exercises that included abdominal massage and rectal digital stimulation during the week leading up to the operation. Patients who did not perform exercises were included as the control group. Participants were randomized after obtaining written informed consent forms. Patients with an operation plan were assigned to one of the two groups through randomization by the principal investigator. Group 1 patients constituted the control group, while Group 2 consisted of patients who regularly performed the recommended bowel exercise program every morning one week before the surgery. The recommended bowel exercise program was explained in detail to patients by the responsible researcher on the day of their preoperative anesthesia preparations (at least 10 days before the surgery) in the pre‐op preparation room, accompanied by visual presentations. The recommended bowel exercise program consisted of three steps: 1. Patients will perform a 2‐3 minute massage starting from the cecum approximately 20‐30 minutes after breakfast, moving along the colon. 2. Patients will assume a suitable position and perform circular massage on the anal walls with their finger for approximately 30 seconds (digital rectal stimulation). 3. Patients will try to defecate while sitting on the toilet.

Nct (2023). "Impact of Time on Sexual Function (FSFI® Score) After Hysterectomy." ClinicalTrails.gov.
	In France, more than 62 000 hysterectomies are performed each year. Female sexual function is the result of multiple psychological, social and physiological factors. There is no information in the current literature about the optimum time between the surgery and the sexual relation resumption. The primary outcome is to assess the impact of advising time between hysterectomy and sexual relation resumption by using FSFI® score. Secondaries outcomes are: to describe and compare post‐operative complications in the two groups of the study, to describe the follow‐up of the recommendation concerning time between surgery and sexual relation resumption and to describe why this recommendation was not followed. This study is based on 4 questionnaires: FSFI® pre‐operative and post‐operative, pre‐operative questionnaire and post‐operative questionnaire. This is a monocentric, comparative, of superiority, randomised and prospective study. Patients are randomised into two groups: sexual relation resumption advised 4 weeks after surgery, or 8 weeks. The inclusion criteria are more than 18 years, francophone, in sexual activity, scheduled for a total hysterectomy for benign indication (menometrorrhagia, fibroma, adenomyosis, endometriosis, pelvic floor disorders, low‐grade endometrial cancer), considering vaginal, laparoscopic and abdominal approach, and a written consent. Non‐inclusion criteria are illiteracy, cognitive disorders, without social security, deprived liberty by judicial or administrative decision, psychiatric care, patient with legal protection, patient incapable of giving consent. If our conclusions confirmed our hypothesis, it can improve clinical practices by providing additional informations for surgeon and patient, to undergo this surgery as serenely as possible.

Nct (2023). "ImpRoving hEalth behaviourS for LIfe After ENdometrial CancEr Trial." ClinicalTrails.gov.
	Background: Individuals diagnosed with endometrial cancer are at an increased risk of cardiac complications post‐treatment, particularly if having overweight or a pronounced waist size. Adopting healthy habits‐like nutritious eating, regular physical activity, and effective stress management‐can mitigate these risks and bolster overall health. However, many cancer survivors find it challenging to consistently adhere to these health and wellness recommendations. Objective: This study aims to determine the efficacy of a web‐based health platform, enriched with professional guidance, in facilitating healthier lifestyles for endometrial cancer survivors. This would encompass enhancements in nutrition, physical activity levels, and mindfulness practices. Study Design: Group 1 (Intervention Group): Participants will engage with the web‐based health platform daily for the initial 16 weeks with expert guidance. Subsequently, participants will navigate the platform independently for the next 8 weeks. Group 2 (Control Group): Participants will initially be provided with standard publicly accessible health information. After the primary 24‐week period, participants will gain access to the web‐based wellness platform. Common Elements: Both groups will have access to general health information and will benefit from supportive calls. To monitor their physical activity, all participants will be equipped with an activity tracker.

Nct (2023). "Improving Maternal Mental Health & SUD Screening and Treatment." ClinicalTrails.gov.
	Aim 1: To determine differences in rates of treatment attendance and retention for Perinatal Mood and Anxiety Disorders (PMADs) and Perinatal Substance Use Disorders (PSUDs) between participants assigned to LTWP, compared to SBIRT. Aim 2: To determine differences in Patient‐Reported Outcomes (PROs) including depressive symptoms, quality of life, substance use, and maternal functioning and well‐being measured at the time of referral (baseline=0) and 2, 5, 8, and 11 months postpartum.

Nct (2023). "IN10018 in Combination With Pegylated Liposomal Doxorubicin (PLD) vs. Placebo in Combination With PLD for the Treatment of Platinum-resistant Recurrent Ovarian Cancer." ClinicalTrails.gov.
	This is a multicenter, randomized, double‐blind, Phase II clinical study to evaluate the efficacy and safety of IN10018 in combination with PLD vs. placebo in combination with PLD in subjects with platinum‐resistant recurrent ovarian cancer (including fallopian tube and primary peritoneal cancers). Approximately 168 subjects will be enrolled into the study. Eligible subjects will be randomized in a 2: 1 ratio to receive IN10018 in combination with PLD treatment (Experimental Arm, N = approx. 112) or placebo of IN10018 in combination with PLD (Control Arm, N = approx. 56). Subjects will be stratified by prior bevacizumab use (yes or no) and platinum free interval (PFI, < 3 months or 3‐6 months). Subjects will be randomized to one of following treatment arms. The investigator should follow the clinical study protocol, the approved label of these drugs and/or institutional standard of care. ‐ Experimental Arm: IN10018 100 mg QD orally (PO) plus PLD 40 mg/m2 once every 4 weeks (Q4W) intravenously (IV). ‐ Control Arm: Placebo of IN10018 100 mg QD orally (PO) plus PLD 40 mg/m2 once every 4 weeks (Q4W) intravenously (IV).

Nct (2023). "Incontinence Analysis After HoLEP Using 28Fr Versus 22Fr Sheath." ClinicalTrails.gov.
	This study will be a randomized controlled trial in which patients who meet inclusion criteria will be randomized to one of two groups, HoLEP performed with either 1) 22Fr sheath set or 2) 28Fr sheath set. After HoLEP, data will be analyzed using chi‐square test for incontinence vs no incontinence between 22Fr and 28Fr groups at 1 week, 4 weeks and 12 weeks post operatively.

Nct (2023). "In-person vs. Virtual Delivery of a Group-based Prevention of Postpartum Depression." ClinicalTrails.gov.
	Depression is one of the most common perinatal complications, with 1 in 7 mothers qualifying for a diagnosis of postpartum depression (PPD) and even higher rates for those who identify as Hispanic/Latine, Black or African American, American Indian, or Alaska Native, or by multiple races or ethnicities. This project addresses this major gap in services to prevent PPD, particularly among socioeconomically disadvantaged and minoritized groups. It tests the benefit of a virtual perinatal preventive intervention in English and Spanish to increase access, scalability and address the mental health needs of underserved populations. This project will test the virtual version against the in‐person version of a service‐ready efficacious preventive intervention in a randomized controlled trial (RCT). This trial will provide a test of a preventive intervention with a strong evidence base that is scalable and can be delivered with fidelity by service providers in settings where obstetric care is received. In this project, pregnant women will be randomized to receive an evidence‐based group prevention program (Reach Out, Stay Strong, Essentials for New Moms; ROSE) designed for perinatal populations either a) in person, delivered at the hospital where they are receiving prenatal care or b) virtually, delivered by the same staff via video conferencing, both offered in English and Spanish. Diverse pregnant individuals (N = 900) will be randomized to receive virtual or in‐person ROSE. The central outcome, depression, will be assessed via REDCap surveys, prenatally (before the program begins and at the end of gestation) and postpartum (approximately six‐weeks, 3, 6, and 12‐months after birth). Electronic health records (EHRs) and surveys will be used to examine obstetric, mental health (e.g., standard of care depression screening), and sociodemographic factors linked to health disparities that may impact who benefits most.

Nct (2023). "Intraperitoneal Bupivacaine for Pelvic Organ Prolapse." ClinicalTrails.gov.
	The purpose of this study is to evaluate the effects of 30 mL intraperitoneal Bupivacaine without epinephrine 0.25% on postoperative pain control in patients undergoing pelvic organ prolapse repair. The investigators hypothesize that use of intraperitoneal Bupivacaine will decrease postoperative pain scores and opiate consumption in the postoperative period, following pelvic organ prolapse repair.

Nct (2023). "An Investigation Into the Efficacy of a Botanical Supplement to Provide Period Relief." ClinicalTrails.gov.
	Women often experience significant pain during their periods which can significantly impact on quality of life. In this study, two products that are used to alleviate period pain will be examined. One test product is botanically based, and the other is a traditional over‐the‐counter pain reliever with additional components added to support less painful periods. The trial will be a cross‐over trial where participants will use the botanical product before, during, and after their first period. Participants will use the botanical product alongside a traditional over‐the‐counter period product during their second period. Participants will answer surveys and have blood drawn at a third‐party lab to answer the main objectives of this trial.

Nct (2023). "Kegal Exercises With and Without Postural Correction on Postpartum Pelvic Organ Prolapse in Primiparous Women." ClinicalTrails.gov.
	The design of this study will randomize controlled trial. Data will collect from the Settings of Jinnah Hospital Lahore, THQ Hospital Depalpur, and Al‐Shifa Hospital Depalpur. The sample size for this study is 30 primiparous women. Participants will be screened for eligibility. Women will be randomly assigned to the training group, which conducts 12 weekly individual sessions. Outcomes will be assessed after the last session. The control group will receive kegal exercise after the initial assessment. Main outcome measures for this study include the symptoms pelvic floor impact questionnaire, the pelvic floor distress inventory questionnaire, and the pelvic organ prolapse quantification examination. The pelvic floor impact questionnaire will assess the lifelong impact of pelvic floor disorders on women. A pelvic floor distress inventory questionnaire will assess distress caused by PFD (pelvic floor dysfunction).

Nct (2023). "Kegel and Abdominal Exercises on Urinary Incontinence Severity, Quality of Life, and Sleep Quality in Menopausal Women." ClinicalTrails.gov.
	Urinary incontinence is defined by the International Continence Society as involuntary urinary leakage that causes social and hygienic problems and can be objectively demonstrated. Urinary incontinence is an important health problem that is more common in women than men. As a matter of fact, urinary incontinence has also been recognized as a common public health problem affecting women's physical, psychological, social, and economic well‐being. This problem may worsen, especially during menopause, as estrogen levels decrease and pelvic floor muscles and ligaments atrophy. Women spend a long period of their lives in menopause. Therefore, the urinary incontinence they experience during this period affects their lives in many dimensions (insecurity, deterioration in sexual life, insomnia, etc.). As a matter of fact, one of the important conservative treatments for urinary incontinence is Kegel exercises. The fact that it has no risks or costs and that women can do it wherever and whenever they want makes this exercise advantageous. It has been reported that abdominal muscle exercises (bridge building and abdominal curling exercises, etc.), along with Kegel exercises, significantly affect the pelvic floor muscles. However, the studies are mostly on the samples of pregnant, postpartum, and reproductive‐age women, and studies on women in the menopausal period are needed. This study will increase awareness of the importance and effect of regular kegel and abdominal exercises in menopausal women with urinary incontinence. Deterioration in sleep quality and chronic insomnia are also quite common (11.8% ‐ 56.6%) problems in menopause. One of the factors that cause sleep problems is urinary incontinence, which causes frequent trips to the toilet and interrupts night sleep. Researchers predicted that reducing the frequency of urinary incontinence experienced by women would positively affect their sleep quality. Data Collection: The data will be collected by the researcher by face‐to‐face interview method in a total of 12 weeks, three face‐to‐face interviews, each interview is experimental group 30 minutes ‐ the control group 20 minutes. Kegel and abdominal exercise training is applied to the experimental group. Only kegel exercise training is applied to the control group. Statistical Methods to be Used: The Statistical Package for the Social Sciences program will be used to analyze the obtained data. The conformity of the data to the normal distribution will be examined by considering the Shapiro‐Wilk test. Parametric methods will be used to analyze normally distributed variables, and non‐parametric methods will be used to analyze non‐normally distributed variables. Independent‐sample T‐test, Mann‐Whitney U (Exact) test, and T‐test for Dependent Groups, Wilcoxon test will be used to compare two independent groups. Pearson correlation Spearman's tests will be used to examine the correlations of the variables with each other. Comparison of categorical data will be tested with Pearson Chi‐square and FisherExact tests.

Nct (2023). "Lacticaseibacillus Rhamnosus CA15 (DSM 33960) Strain as a New Driver in Restoring the Normal Vaginal Microbiota." ClinicalTrails.gov.
	The aim of the present randomized double‐blind placebo‐controlled study is to evaluate the ability of the potential probiotic Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain, orally administrated, to balance the vaginal microbiota of women with vaginal dysbiosis. Two hundred women, with signs and symptoms of vaginal dysbiosis, are recruited and randomly allocated to receive oral capsules containing the L. rhamnosus CA15 (DSM 33960) strain or placebo once daily for 10 days. Clinical and microbiological parameters are evaluated in three scheduled appointments: at baseline (T0), 10 days after the start of the treatment (T1), and 30 days after the end of the treatment (T2). In addition, at baseline (T0) and 30 days after the end of the treatment (T2), the quality of life will be evaluated through a quality of life assessment questionnaire.

Nct (2023). "Laparoscopic Sacropexy and Vaginal Natural Orifice Transluminal Endoscopic Surgery Shull Suspension Comparison Trial." ClinicalTrails.gov.
	patients with pelvic organ prolapse with a stage greater than or equal to stage 2 for the apical compartment who are candidates for surgical correction will be randomized and assigned to one of two treatment groups. The aim is to compare the anatomical, surgical and anesthesiological outcomes between these two surgical techniques, both of which are commonly used in clinical practice for the correction of this type of prolapse.

Nct (2023). "Laparoscopic Therapy of Endometrioma: sclerotherapy vs Cystectomy in Patients With Unfinished Reproductive Plans." ClinicalTrails.gov.
	Only patients who sign informed consent will be included. Only patients wishing for future pregnancy will be involved in the study. Expected number of enrolled subjects is 160 ( 80 in each arm) Patients with endometrioma and planned surgery to remove it will be randomized either to laparoscopic sclerotherapy with 96% ethanol or cystectomy. First AMH sample will be taken day before surgery. If other endometriosis lesions (deep or superficial) are present, they may be also resected during this surgery. Ethanol sclerotherapy description: classical laparoscopic approach ‐ small (max1cm) fenestration of endometrioma ‐ aspiration of endometrioma contents‐ foley catheter insertion‐ ballon inflation inside of the cyst‐ instillation with 96% ethanol which is left in the cyst for 10min‐ aspiration of ethanol and flushing with saline. Cystectomy: classical laparoscopic approach‐ large fenestration of endometrioma ‐ aspiration of endometrioma contents‐ indentification of ovary/ endometrioma tissue and plane between the ovarian capsule and cyst wall is developed using a mix of blunt and sharp dissection ‐ if bleeding is present it is stopped by cautious bipolar coagulation visit 1 ‐ surgery time (AMH day before surgery, age, BMI, endometriosis extent, gravidity/ parity, endometriosis residue after surgery, pain levels) visit 2‐ 3 months after surgery : Ultrasound, complications, pregnancy, asissted reproduction, pain levels visit 3+4 ‐ 6/12months after surgery: AMH, Ultrasound, complications, pregnancy, asissted reproduction, pain levels visit 5‐ 24 months after surgery: Ultrasound, complications, pregnancy, asissted reproduction, pain levels

Nct (2023). "LATe Cerclage in High-risk Pregnancies (LATCH)." ClinicalTrails.gov.
	Singleton high‐risk pregnancies < 24 weeks of gestation will be screened for enrollment and randomized, if a short TVU CL (≤25mm) is detected between 24 0/7 ‐ 26 6/7 weeks, to either cervical cerclage or control (no cerclage). Aside from cerclage placement, management of included women will be the same including recommendation for continuing or initiating daily vaginal progesterone 200mg from randomization until 36 6/7 weeks. The primary outcome will be the incidence of preterm birth <37 weeks.

Nct (2023). "Lidocaine Patches Prior to Percutaneous Nerve Evaluation." ClinicalTrails.gov.
	The study design will be a double‐blind randomized control trial comparing 4% lidocaine patch placed over the sacrum 30 minutes prior to the procedure to placebo patch. Intervention and control patches will be in envelopes labeled with study number and located within the procedure area. A patch from the envelope corresponding to the patient will be placed by a medical assistant or co‐investigator who is not associated with the PNE placement procedure 30 minutes prior to the procedure start. Number of voids and incontinence episodes per day prior to the PNE procedure will be recorded. A patch (intervention or control) will be removed by a medical assistant prior to provider entering the room in order to secure blinding. 1% lidocaine 10cc will be injected into the sacral procedure site for adequate pain relief. PNE procedure will then be performed. If inadequate analgesia is reported by the Patient during the procedure, additional injectable lidocaine will be administered in 5 cc increments, not to exceed 4.5 mg/kg of injectable lidocaine. The volume of injectable lidocaine used will be recorded. VAS pain scores prior to and immediately after procedure will be recorded. Patient Satisfaction Score, rate of successful PNE, rate of progression to SNS implantation, and amplitude of perineal stimulation of a Likert scale will be collected immediately after the procedure. Patients will follow up in 1 week ‐ as is standard of care with the PNE procedure. Adverse events such as pain or change in sensation will be recorded. Number of voids and incontinence episodes per day after the PNE procedure will be recorded. The overall satisfaction score will be recorded at that time.

Nct (2023). "Listening Music, Drawing on Coping With Dysmenorrhea Complaints of Nursing Students." ClinicalTrails.gov.
	This three‐armed randomized controlled study (RCT) will be conducted in July 2023 in Bartın University Faculty of Health Sciences Nursing Department students experiencing dysmenorrhea. Nursing students who experienced dysmenorrhea at the time of application were informed about the aims, setup and intervention of the study. and evaluated for suitability in a short, standardized interview. Nursing students experiencing dysmenorrhea who met our criteria were given a basic questionnaire along with a letter of information and an informed consent form. Nursing students with dysmenorrhea gave written informed consent for participation in the study were included. Evaluations in all three groups were made before randomization (ie baseline) and immediately after the intervention periods (2nd and 3rd month). Randomization: The randomization list was made by another scientist who was not involved in the research process in order to preserve the random selection order and to prevent bias, and with this blinding applied, the group allocation was hidden. A computer randomization program was used to generate the randomization list for the intervention allocation sequence. Individuals who received a voluntary consent form and volunteered to participate in the research were randomly assigned to the experimental and control groups by using the blocking method. Following simple randomization procedures, participants were assigned to one of the three arms of the study in a 1:1:1 ratio according to a computer‐generated randomization scheme via https://www.sealedenvelope.com/simple‐randomiser/v1. In this research, the allocation of participants to groups was made by scientists who were not involved in the research. Due to the nature of the research, the follow‐up of the practices and the participants will not be provided during the data collection process, as the researcher does it. Intervention: Music Group: In the second and third months, participants listened to a song that lasted 29 minutes and 32 seconds for four days (three days before menstruation and the first day of menstruation). The song to be played was determined by examining the literature, the song was composed by researcher Juan Sebastian Martin‐Saavedra and was named Occasio Adolore (Music Piece No. 5‐559‐355 and Phonogram No. 12‐105‐295) by the author copyright institution of Colombia. registered under. While the researcher is composing the song, it is to create a piece of music that will reduce the pain felt, activate positive emotions and relax the person. The composed song is available online within the scope of the published article (https://soundcloud.com/jss‐martin/occasio‐adolore). Written permission was obtained from Juan Sebastian Martin‐Saavedra to use the composed song in the research. The access link of the composed song will be sent to the participants via social media (WhatsApp). After listening to music for three days before the menstrual cycle and on the first day of menstruation (for a total of four days), pain, menstrual symptoms and perceived stress on the first day of menstruation will be measured using VAS, MSS, and PSS, respectively. Drawing Group: In the second and third months, the participants will be asked to paint for 29 minutes and 32 seconds (the duration of the intervention was determined in parallel with the music group in order not to create variability between the groups) for four days (three days before menstruation and the first day of menstruation). The type of paint to be used in the drawn picture (dry pen, crayon or watercolor) is left to the availability of the participants, and it will be stated that they prefer colors and drawings that will raise their emotions, focus their drawings and feed positive emotions in the picture to be drawn. After drawing pictures three days before the menstrual cycle and the first day of menstruation (for a total of four days), pain, menstrual symptoms, and perceived stress on the first day of menstruation will be measured using the VAS, MSS, and PSS, respectively. Control G up: Nursing students with dysmenorrhea in the control group were informed that drawing and listening to music practices would be performed after the initial, second and third month evaluations of the study. In the meantime, it was stated that he should not make any interventions other than her routine applications. At baseline, second, and third month, participants will measure pain, menstrual symptoms, and perceived stress on the first day of the menstrual cycle using the VAS, MSS, and PSS, respectively. Measures: "Personal Information Form", "Visual Analog Scale (VAS)", "Menstruation Symptom Scale (MSS)" and "Perceived Stress Scale (PSS)" were used in the study. Personal Information Form: It consists of a total of 36 questions, including socio‐demographic characteristics and features related to the menstrual cycle. Within the scope of socio‐demographic characteristics; age, height, weight, bki, mother's education level, mother's employment status, father's education level, father's employment status, income status, family type, smoking status, alcohol use status, physical exercise status, place of residence during education life, heavy There are questions such as dominant personality structure, perspective on life. Within the scope of the characteristics related to the menstrual cycle, the first menarche age, the duration of the menstrual cycle, its frequency, the regularity of the menstrual cycle, the reaction of waiting to be menstrual before the menstrual cycle, the feeling of cramp‐like pain (dysmenorrhea) in the lower part of the abdomen in the first days of the menstrual cycle, the state of feeling experienced during the menstrual cycle. Problems and coping methods, duration of dysmenorrhea complaint, use of pharmacological treatment method in dysmenorrhea, use of traditional and alternative treatment methods in dysmenorrhea, information source and sharing with a health professional if using, status and frequency of applying to the emergency department with dysmenorrhea complaints are included. The questions were prepared by the researchers in line with the literature, and expert opinion was taken after the questionnaire was prepared. Visual Analog Scale (VAS): The intensity of menstrual pain will be measured using the VAS, a valid and reliable tool to measure experimental and clinical pain. The VAS is scored on a horizontal line of 10 cm (0=no pain and 10=worst possible pain). The Menstruation Symptom Scale (MSS): This scale was developed in English by Chesney and Tasto in 1975 to assess menstrual pain and symptoms. It is a widely used scale in the United States and many different countries. The factor structure and usability on adolescents were reassessed and updated. The adaptation of the scale to Turkish was done. Participants are asked to give a number between 1 (never) and 5 (always) for the symptoms they experience about menstruation. The items of the scale are numbered according to the factors set aside for ease of use. 1‐13. The items belong to the "Negative effects/somatic complaints" sub‐dimension, 14‐19. Items included in the "Menstrual pain symptoms" sub‐dimension and 20‐22. items belong to the sub‐dimension "Coping methods". Cronbach's Alpha value is 0.86. It is a five‐point Likert‐type scale consisting of 22 items. The score obtained from the sub‐dimensions is calculated by taking the total score average of the items in the sub‐dimensions. The increase in the mean score for the sub‐dimensions indicates that the severity of menstrual symptoms related to that sub‐dimension increases. Perceived Stress Scale (PSS): This scale is a self‐rating scale developed. The total score that can be obtained from the scale is 32. A high total score from the scale, which consists of 10 items and scored between 0‐4, indicates a high level of stress. In this study, the scale whose Turkish validity and reliability study was conducted was used. Sample size calculation for the primary research question was performed based on a pilot study. Power analysis of this research was done with G OWER 3.1.9.7 (Power analysis statistical software). In determining the sample size, the value of menstrual pain intensity was taken as the basis. It was determined that 28 individuals from each group would be sufficient to participate in the study, with an effect size of 0.75, margin of error of α=0.05 and minimum power=80% (β=0.2). However, considering the possible missing data, it was decided to include 32 female nursing students in the study by making 10% increase in each group.

Nct (2023). "Live Birth Rate After Sperm Selection Using ZyMōt Multi (850µL) Device for Intra Uterine Insemination." ClinicalTrails.gov.
	Intrauterine insemination is a commonly used method for Medically Assisted Reproduction for patients with mild male factor infertility, anovulation, endometriosis, and unexplained infertility. It is also the procedure of choice in cases of lesbian couples or single women, using donor sperm. During the IUI procedure, the sperm suspension is introduced into the uterus through the cervix canal using an insemination catheter containing 0.4 ml sperm. Before sperm can be used in IUI, it must first be processed. The aim of semen preparation is to select the best sperm cell population (highly motile, morphologically normal spermatozoa with minimal DNA damage) with the highest fertilization potential. One of the most used sperm preparation technique is DGC. This technique allows the separation of sperm cells based on their density. Morphologically normal and abnormal spermatozoa have different densities. A mature morphologically normal spermatozoon has a slightly higher density, whereas an immature and morphologically abnormal spermatozoon has a lower density. During this procedure, raw semen sample is placed on 2 gradients: a lower phase (80%) and an upper phase (40%) followed by centrifugation. The composition of the gradients include a colloidal suspension of silica particles. At the end of centrifugation, each spermatozoa is situated at the gradient level that matches its density. The highly motile, morphologically normal, viable spermatozoa form a pellet at the bottom of the tube. This procedure is relatively easy to perform but both the centrifugation steps and the silica particle are considered to have a negative impact on DNA integrity. Recently, microfluidic technology was introduced as an alternative to the conventional sperm sorting techniques. As this procedure does not require semen processing, it reduces the sperm preparation time and eliminates sperm DNA damaging procedures (e.g. by centrifugation). This technology is a chemical‐free method of sorting healthy normal sperm using a sterile disposable ZyMōt Multi (850µL) sperm separation device. Sperm selected by this device proved to have better motility and less DNA damage compared to DGC procedure. More recently, the efficacy of this device has been reported to significantly increase ongoing pregnancy rate when compared with DGC in IUI cycles. However, large, correct studies that investigate live birth rate are missing. The present study aims to determine whether the use of ZyMōt Multi (850µL) device for sperm selection improves the live birth rate in IUI patients as compared to the standard DGC procedure. Couples undergoing IUI procedure will be included in the study if they are planned for IUI with fresh autologous ejaculate. Patients that fulfill the inclusion criteria will be randomly allocated to one of the two sperm selection methods: DGC (standard) or ZyMōt Multi (850µL) device (treatment) groups. The randomization will be performed based on an electronically generated list. A patient participation to the study will be limited to 3 consecutive IUI attempts (within a period of 6 months). Same semen preparation protocol used in the 1st IUI attempt [ZyMōt Multi (850µL) or DGC] will be used in the next 2 consecutive IUIs. Following the IUI procedure (with sperm selected with either one of the two methods), the patients will be monitored for pregnancy, clinical pregnancy and neonatal outcome.

Nct (2023). "Local Anesthesia Before Bulkamid Injection." ClinicalTrails.gov.
	While recommended pre‐anesthesia for polyacylamide hydrogel (PAHG, Bulkamid) injections for stress urinary incontinence and intrinsic sphincter deficiency can include intraurethral anesthetic gel with or without periurethral block, there is no existing literature to guide choice of anesthesia. This is a single‐blinded randomized control trial to evaluate post‐procedure pain with choice of anesthesia before PAHG injection.

Nct (2023). "Long-term Success Rate of Transvaginal Mesh for the Treatment of Pelvic Organ Prolapse: the Extended RCT Study." ClinicalTrails.gov.
	The previous study is a randomized trial designed to compare the composite success rate between patients with self‐cut mesh procedure and those with mesh‐kit procedure. The original RCT study includes a 1‐year follow up from the time of surgery, which is too short to evaluate the long‐term sequelae of the surgical procedures. The goal of this long‐term follow‐up study is to extend the follow‐up of women in the previous RCT study up to 10 years from the time of surgery and to compare the success and complication rates of the two surgical treatment groups over this extended time period. The primary aim is to determine whether treatment success in women who undergo the above strategies differ at time points through 10 years. A supplemental study investigates the long‐term success rate and complications of transvaginal mesh procedure in women in both of the study arms.

Nct (2023). "Luteal Phase Support With GnRH Agonist After GnRH Agonist Triggering in IVF/ICSI Cycles." ClinicalTrails.gov.
	It is currently established that obtaining a large number of oocytes is a key of success in IVF/ICSI cycles. However, it is also a risk factor for ovarian hyperstimulation syndrome (OHSS) and a risk factor of implantation failure after fresh embryo transfer because of the alteration of endometrial receptivity. A freeze all strategy can be proposed to avoid these risks but vitrification of embryos, although more efficient than slow freezing in terms of embryo survival, is not without risk. Furthermore, proper endometrial and embryo timing for frozen‐thawed embryo transfer is still debated. Recent preliminary works suggest another possible way to combine an optimal ovarian response with the recovery of a large number of oocytes, good chances of implantation and a reduced risk of OHSS. To achieve this goal, ovulation triggering and luteal phase support need to be modified together. The human chorionic gonadotropin (hCG) (mimicking the Luteinising Hormone (LH)peak to trigger ovulation) that induces OHSS is replaced by an a GnRH agonist (GnRHa) triggering allowing an endogenous peak of Follicle Stimulating Hormone (FSH) and LH. Then, the usual support of the luteal phase by exogenous vaginal progesterone, whose absorption seems to be suboptimal for about 30% of patients, is replaced by endogenous progesterone production by the corpora lutea, supported by the maintenance of LH activity through the continuation of agonist of gonadotropin releasing hormone (AgoGnRH) in the luteal phase. Pilot studies show that a 10% to 15% increase in ongoing pregnancy rates can be expected with this type of protocol. The objective of our study is to demonstrate an increase in ongoing pregnancy rate per cycle with this new strategy combining GnRHa triggering and GnRHa luteal phase support compared to the reference protocol (hCG triggering and exogenous progesterone luteal phase support).

Nct (2023). "Management of Cancer Therapy Related Vulvovaginal Atrophy." ClinicalTrails.gov.
	1. The first group will receive two treatment of sub‐mucosal PRP injection at the outer 3 cm of the vagina with one month interval in between. (17) 2. The second group will receive two treatment of PRP injection mixed with non‐cross linked hyaluronic acid at the outer 3 cm of the vagina with one month interval in between. 9. 3‐The third group will receive one applicator (5gm) three times per week of topical hyaluronic acid gel for vaginal application which will be prepared in the faculty of pharmacy for 2 months. Clinical assessment Patients will be assessed for symptoms and signs of vulvovaginal atrophy (VVA) at baseline, one month, two months, and, three months after the end of treatment. 1. Vulvovaginal atrophy (VVA) symptoms (dryness, dyspareunia) will be assessed on a subjective 10‐point scale. Also, patient satisfaction with each type of treatment will be assessed with a questionnaire at the end of treatment and they will be asked if they wish to repeat the treatment to maintain effectiveness over time (yes or No). 2. For assessment of VVA signs on physical examination, vaginal health index including assessment of pH, overall elasticity, epithelial mucosa, fluid secretion type, and consistency and moisture will be used as an objective method of evaluation of therapy. 3. Assessment of sexual satisfaction of both male and female partners: Sexual satisfaction was measured using the Arabic version of the Index of Sexual Satisfaction (ISS) and female sexual function index (FSFI) questionnaire.

Nct (2023). "Management of OAB in Female Patients." ClinicalTrails.gov.
	The objective of this study is to compare the effectiveness of mirabegron, solifenacin, tadalafil (5mg), and their combination in relieving symptoms of overactive bladder (OAB) in a double‐blinded prospective randomized placebo‐controlled trial.

Nct (2023). "Mandala Activity Accompanied With Two Different Music on Infertility." ClinicalTrails.gov.
	In this study; In this study, it is aimed to determine the stress level and the effect of the mandala activity, which is applied to two different musical accompaniments, on coping with stress in infertile women who have undergone embryo transfer. The research was carried out as a randomized controlled experimental study with women who had embryo transfer at Private Samsun Medicana International Hospital IVF Center and Private Samsun VM Medical Park Hospital IVF Center between 01.07.2021 and 31.07.2022. Introductory Information Form, Infertility Stress Scale (PSS), and Infertility Stress Coping Scale (PSSS) were applied to intervention groups with embryo transfer. The intervention group started right after the embryo transfer and performed a mandala activity accompanied by music or meditation music of their own choosing until the day before the BetaHcg test, and the ISS and PSS were repeated one day before the BetaHcg test. Both groups were provided with the application for at least 7‐10 days. After embryo transfer to the control group, Introductory Information Form, PSS and PSS were applied, and PSS and PSS were repeated one day before the BetaHCG test, and no intervention was made other than routine practices.

Nct (2023). "Maternal Mental Health Access - MaMa." ClinicalTrails.gov.
	This type1 hybrid effectiveness‐implementation project is conducted within healthcare settings and underserved populations (rural, urban, and Latino) and for individuals who are at risk for perinatal depression (PD), which allows the team to refine the approach in preparation for a future effectiveness trial for the prevention of PD in diverse communities using accessible Digital Mental Health Technology (patient education portal, FB discussion boards, synchronous videoconference support sessions). The plan is to adopt a randomized preference trial design to assess the impact of patient preference and sociocultural factors (including race, ethnicity, and geographic residence) on engagement and preliminary results. This information is crucial for a subsequent trial and for ultimately taking the intervention to scale. The study design using the IRLM reflects scientific rigor that can be reproduced by other investigators. The implemented strategies specifically developed to optimize implementation success, and to measure the implementation outcomes of these strategies and include valuable input from key informants, stakeholders, and the Community Advisory Board at regular intervals throughout the project time period.

Nct (2023). "The Mediterranean Diet and Bacterial Vaginitis." ClinicalTrails.gov.
	In the study, 256 patients were diagnosed with vaginitis in the Obstetrics and Gynecology clinic. BV was diagnosed in 189 (73.8%) of the patients. Twelve patients with a diagnosis of BV who did not want to participate were excluded from the study. The Mediterranean diet was recommended and explained to 113 of the remaining 177 patients. 49 (42.5%) patients were excluded because the Mediterranean Diet Adherence Scale was <7. 64 (57.5%) patients who were on a diet and had a Mediterranean Diet Adherence Scale ≥7 were included in the diet group (group 1) As the control group (group 2), 64 patients participated in the study. A randomized controlled study was designed to investigate the effect of the Mediterranean diet on the treatment of vaginitis in patients diagnosed with BV and given medical treatment. The study was carried out with the collaboration of the Gynecology and Obstetrics Clinic and Diet Clinic. Patients diagnosed with BV and given medical treatment were divided into two groups a diet group and a control group. Patients who were diagnosed with BV, given medical treatment, and recommended a Mediterranean diet, whose dietary compliance was controlled and compliant with the Mediterranean diet control questionnaire, who came to the control examination after two weeks and were accepted to participate in the study, were included in the diet group. Patients diagnosed with BV, given medical treatment, followed up two weeks later, and accepted to participate in the study were included in the control group. In the control examination, the patients were grouped and compared as responsive and resistant after treatment. Data collection Demographic data (age, gender), anthropometric measurements, presence of comorbid disease, menopausal period, presence of diabetes mellitus (DM), medical history, an average of three‐day food consumption, and results of vaginitis treatment in the control examination of the patients included in the study were recorded. In addition, the patient's birth history, delivery technique, vaginal operation history, and vaginitis history were questioned in her medical history. Anthropometric measurements Body weight (kg), height (cm), total body and abdominal fat ratio of each patient were measured and recorded by the researcher. Body weights were measured by the dietitian using a standard weighing instrument sensitive to 100 g without shoes. Values were determined in kilograms. Height measurements were taken with a Harpenden Stadiometer without shoes, heels touching, feet open at 45º, arms hanging at attention, head in frankfort plane. Values were determined in centimeters. BMI was calculated with the formula of body weight/height squared. Total body and abdominal fat ratio were measured with Tanita. According to the international BMI classification of the World Health Organization; 30 kg/m² was classified as obese (17). Nutrient consumption analysis The patients were asked to write a diary of the foods they consumed while coming to the control examination. In order for the diary of the foods records to be reliable, tea glass, water glass, bowl, dessert spoon, tablespoon, serving spoon, ladle, 1 slice of bread, 1 meatball measure of meat, chicken, fish, 1 slice of cheese and their quantities were shared visually. Detailed information was given with replica samples.The foods consumed daily were recorded in the Bebis program. The amount of energy received by the patients from the average daily food consumption (kcal/day), what percentage of the daily energy was obtained from carbohydrates (%), and daily protein and fiber consumption amount (gr) were calculated. The distribution of protein consumption amount as animals and vegetables was investigated. The frequency of daily consumption of vegetables, fruits, and grains was recorded. Mediterranean diet compliance questionnaire The adherence to the Mediterranean diet of the patients in the diet group who came to the control examination was evaluated with the 'Mediterranean Diet Adherence Scale'. The scale includes the type of oil used by the par cipants in meals, daily olive oil consumption, fruit and vegetable portions, margarine‐butter and red meat consumption, weekly wine, pulses, fish‐sea products, nuts, pastry consumption, tomato sauce. olive oil and white meat instead of red meat. It consists of 14 questions about the choice, to which all points are added by taking 1 point or 0 points for each question asked according to the consumption amount of the participant (18). Patients with a Mediterranean Diet Adherence Scale score >7 were considered compliant with the diet and were included in the study. Diagnosis and treatment of bacterial vaginitis The obstetrician and gynecologist made the diagnosis of BV. Vaginal culture and microbiological examination were applied by the physician when necessary. Oral or vaginal antibiotics (metronidazole, clindamycin) were administered according to the BV physician's preference.

Nct (2023). "Microfluidic Chip vs Density Gradient Centrifugation on the Euploidy Rate of Pre-implantation Genetic Testing." ClinicalTrails.gov.
	The study aims to investigate the treatment of couples undergoing in vitro fertilization (IVF). Eligible couples will be recruited for the study after providing informed written consent following counseling. The IVF protocol involves various steps. Women will undergo preimplantation genetic testing (PGT) as clinically indicated. Ovarian stimulation will be carried out using gonadotropin injections, and regular ultrasound monitoring will be conducted to track the growth of follicles. To prevent a premature LH surge, progestin primed ovarian stimulation or a GnRH antagonist will be administered. Once at least three follicles reach a size of over 17 mm, a trigger injection of either human chorionic gonadotrophin or a GnRH agonist will be given to induce final maturation. Oocyte retrieval will be performed 36 hours after the trigger under transvaginal ultrasound guidance. The recruited women will be randomly assigned to one of two groups: the microfluidic chip group or the density gradient centrifugation group. Randomization and blinding will be ensured to maintain the integrity of the study. Only the laboratory staff involved in sperm preparation will be aware of the group assignment, while the women and clinicians will be blinded to the treatment groups. Semen specimens will be collected by masturbation on the day of oocyte retrieval, following a period of 2‐7 days of sexual abstinence. The semen samples will undergo evaluation according to WHO guidelines, including semen volume, sperm concentration, and percent motile spermatozoa. Sperm DNA damage will be assessed using an alkaline single‐cell gel electrophoresis (Comet) assay. The extent of DNA damage in spermatozoa will be examined using specific parameters. Sperm preparation will be performed based on the randomization list. In the microfluidic chip group, the Sperm Separation Device will be used, and the prepared sample will be collected in a test tube. In the density gradient centrifugation group, sperm preparation will be completed using a discontinuous density gradient centrifugation method, and the resulting sperm pellet will be washed and resuspended. Oocytes will be fertilized through intracytoplasmic sperm injection, and normal fertilization will be confirmed by the presence of two pronuclei. A few cells will be taken from the blastocysts for comprehensive chromosome analysis. Cryopreservation of all blastocysts will be done, and only euploid blastocysts without aneuploidies will be replaced in subsequent frozen embryo transfer cycles. Frozen embryo transfer (FET) will be performed in subsequent natural or hormonal replacement cycles, depending on the women's menstrual cycle regularity. Pregnancy outcomes will be monitored through urine pregnancy tests and transvaginal ultrasounds. If the pregnancy test is positive, further ultrasounds will be done to confirm fetal viability and the number of fetuses. Pregnancy and delivery data will be retrieved after delivery, and information on pregnancy outcomes, number of babies born, birth weights, and obstetric complications will be recorded. The study aims to assess the effectiveness of the two different sperm preparation methods and their impact on IVF outcomes, including pregnancy rates and obstetric complications.

Nct (2023). "Mindfulness in Childbirth Preparation Education Process." ClinicalTrails.gov.
	This prospective, randomized controlled study was conducted to determine the effect of Mindfulness‐Based Childbirth Education on psychosocial outcomes in pregnant women. In this randomized controlled intervention study, the "Consolidated Standards for Reporting Studies (CONSORT) 2018" guideline was followed. It was conducted with pregnant women who applied to Istanbul University‐Cerrahpaşa, Cerrahpaşa Medical Faculty using Zoom program, a web‐based application. Faculty of Medicine, Department of Obstetrics and Gynecology, Pregnancy Polyclinic and Faculty Member Polyclinic, between 15.09.2021‐28.06.2022. A total of 82 pregnant women were included in the experimental and control groups. Preliminary Preparation and Creation of Education Content: The primary researcher (SOA) who provided the training received a Certificate of Mindfulness and Childbirth Preparedness Trainer Training. In order to evaluate the suitability of the content and scope of the Mindfulness‐Based Childbirth Education, which was prepared in line with the literature, to the training received by the researcher, the opinions of 4 experts working on mindfulness and childbirth preparation training were obtained. The content of the training was prepared in line with the feedback received from the experts. Eight sessions were carried out as a pilot application to four pregnant women in order to determine the suitability of the content of the Mindfulness‐Based Childbirth Education Training, to plan the duration of the training and to determine the points that were not understood in the training. At the end of the pilot application, the training content was finalized. Pilot application data were not included in the study. Group Formation: The groups were randomized into two groups by an independent researcher using the web‐based randomization program randomizer.org. Pregnant women who met the inclusion criteria were assigned numbers according to the sequence numbers obtained using the randomization program. Interventions: Information‐Based Childbirth Education: The content of Information‐Based Childbirth Education includes topics such as "Physical and mental preparation for childbirth, the birth process, non‐drug methods that reduce birth pain and facilitate birth, postpartum period characteristics, physiological and psychological changes in the mother after birth, adaptation to the role of motherhood. newborn care." Since the pregnant women were included in the study starting from the 20th week, pregnancy‐related topics were not included in the training content. The training program is organized for four hours each week for four weeks. At least four pregnant women attended each session. It was completed on the alternative training day planned for pregnant women who could not attend. Participants were given homework assignments at the end of each session and asked to complete these assignments by the next training session. After the training, the postpartum women were reminded weekly via WhatsApp until the end of the fourth week after the birth of the baby. Mindfulness‐Based Childbirth Education: In addition to the topics covered in the Information‐Based Childbirth Preparation Training, mindfulness, mindfulness attitudes, practices, mindfulness in daily life, pregnancy and postpartum period, mindful breastfeeding and meditation practices are included. It is recommended that Mindfulness‐Based Childbirth Education should include nine sessions lasting three hours per week and one full day of rest, and the ninth session should be held as a "meeting" after delivery. However, in our study, the participation of pregnant women in the training program was taken into consideration and in order to prevent loss of participants, the trainings were implemented as 2.5 hours and one full retreat day every week for eight weeks, as in many practices. There are studies on this subject in the literature. Considering the participants' unavailability on training days, an alternative training day was planned once a week. In the study, a minimum of f r and a maximum of nine people participated in group trainings. At the end of each training session, a meditation practice lasting approximately 20 minutes was performed. At the end of each session, participants were told how to perform informal mindfulness practices (mindful eating, drinking coffee, walking) at home and were asked to repeat the formal meditation practices taught until the next training session. After the training, postpartum women were reminded weekly until the end of the fourth postpartum week to perform the formal and informal meditation practices included in the training provided within the scope of the study. Data Collection: The licensed Zoom program, a web‐based application, was used to deliver the training. A separate WhatsApp group was created for both groups in the study. Before starting the Prenatal Preparation Training, the first part of the Introductory Information Form, Perceived Stress Scale, Birth Self‐Efficacy Scale and Edinburg Postpartum Depression Scale was created with Google Forms and the link was sent to the WhatsApp groups. Pregnant women in the groups filled out the forms using this link. After the Preparation for Childbirth Training ended (at the end of the eighth week for the Intervention group and at the end of the fourth week for the Control group), the Perceived Stress Scale, the Self‐Efficacy in Childbirth Scale, and the Edinburgh Postnatal Depression Scale, linked to Google Forms, were sent to the WhatsApp groups. Pregnant women in the groups filled in the forms using this link. In the fourth week after delivery, the second part of the Descriptive Information Form created with Google Forms and the link to the Perceived Stress Scale, Edinburgh Postnatal Depression Scale and City Birth Trauma Scale were sent to the WhatsApp groups. Postpartum women in the groups completed the forms using this link. Data Collection Tools Introductory Information Form: The form prepared in line with the literature consists of two sections and a total of 28 questions. In the first part of the form, there are a total of 20 questions evaluating the socio‐demographic characteristics of pregnant women (12), descriptive characteristics such as alcohol habits and physical activity status (6) and birth history (2). In the second part, there are 8 questions evaluating the characteristics of the postpartum period. Perceived Stress Scale (PSS‐14/PSS): The scale consists of a total of 14 items and evaluates individuals' stress perceptions against certain situations they encounter in their lives. The scale has a five‐point Likert rating. The scale has two subscales called "perception of insufficient self‐efficacy" and "perception of stress/discomfort". Items 4, 5, 6, 7, 9, 10, 13, which contain positive statements, are reverse scored. The lowest score that can be obtained from ASÖ‐14 is 0 and the highest score is 56. An increase in the scores people get from the scale indicates that their perception of stress increases. In the original development study of the scale, the Cronbach's alpha coefficient of PSS‐14 was found to be 0.84. In our study, the Cronbach's alpha coefficient of the scale was found to be 0.65. Childbirth Self‐Efficacy Scale (CBSEI): The 62‐item scale developed by Lowe was later developed by Ip et al. (2008) and abbreviated it as the Short Form of the Labor Self‐Efficacy Scale. The scale evaluates women's self‐efficacy level regarding labor. The CBSEI Likert‐type scale has two subscales, outcome and competence expectancy, each consisting of 16 items. The first 13 items in competence expectation are reverse scored. The minimum score to be obtained from each sub‐dimension of the scale is 16 and the maximum score is 160. The minimum score to be obtained from the entire scale is 32, and the maximum total score is 320. Increasing scores on the scale indicate that pregnant women's self‐efficacy levels in labor are high. Edinburgh Postnatal Depression Scale (EPDS): The 4‐point Likert‐type scale consists of a total of 10 questions assessing the psychological s te of the respondent in the last week. It evaluates the risk of depression during pregnancy and postpartum period, but is not a measurement tool that can diagnose depression on its own. The lowest score that can be obtained from EPDS is 0 and the highest score is 30. 7 items (3,5,6,7,8,9,10) in the scale are reverse scored. The cut‐off point of the scale is 12, and women with a total scale score of more than 12 are considered to be in the "risk group" for depression. City Birth Trauma Scale (CBSEI‐C32): The four‐point Likert‐type scale consists of 29 items and five sub‐dimensions. Sub‐dimensions; re‐experiencing, avoidance symptoms, negative cognitions and mood, hyperarousal and dissociative symptoms.CBSEI is used to evaluate the symptoms of Post‐Traumatic Stress Disorder (PTSD) and is not a diagnostic tool. Levels 1‐2 on the scale. substances stress, 3‐7. Items describe symptoms of re‐experiencing labor, items 8‐9. items avoidance symptoms, 10‐16. questions about negative cognitions and mental state symptoms, 17‐22. Items assess symptoms of overstimulation. 3‐22. In the items, people rate the questions asked about their last week as "never", "1 time", "2‐4 times", "5 or more times". 3‐22. The total score range for the items is 0‐60. An increase in the score obtained from the scale means that post‐traumatic stress symptoms are more common and reflects a greater risk for Post‐Traumatic Stress Disorder (PTSD).

Nct (2023). "Mindfulness-Based Cognitive Therapy Postpartum Mothers Stress, Postpartum Blues, Mother-Baby Attachment and Breastfeeding." ClinicalTrails.gov.
	This two‐arm randomized controlled trial (RCT) was conducted in the postpartum mothers located in Edirne, between April and December 2022. During the intake, postpartum mothers were informed about the goals and setup of the study and intervention, and assessed for eligibility by a brief standardized interview. Postpartum mothers who fulfilled our criteria received an information letter and informed consent form, as well as the baseline questionnaire. Those postpartum mothers that provided written informed consent for participation were included in the study. Assessments in both groups were performed before randomization (i.e., baseline) and directly after the intervention period (i.e., post‐measurement, approximately 2 months after baseline). Randomization: Postpartum mothers were randomly assigned to an 8‐week MBCT or control condition. A research assistant not actively involved in the design and data analysis of the study created a random distribution sequence and assigned participants to one of the two conditions (1:1 ratio). Intervention: Mindfulness‐Based Cognitive Therapy (MBCT) is a structured group intervention developed. The intervention consisted of eight weekly 2.5‐hr sessions and one 3‐hr silent session. The main aspects of the program; It included group meditation, cognitive‐behavioral exercises, psycho‐education, and daily homework. The intervention in our study closely followed the original manual, with several adaptations for the study group and purpose. First, psycho‐education focused on the importance of recognizing personal feelings and the relationship between stress, postpartum blues, mother‐infant attachment and breastfeeding symptoms, and stress management, stress, postpartum blues, mother‐infant attachment and breastfeeding. Control Condition: Postpartum mothers in the control condition were informed that they would receive MBCT after a waiting period of 2 months. Meanwhile, no psychological intervention was ofered. Measures: The baseline questionnaire included questions about demographic, socioeconomic, obstetric, mood, and breastfeeding‐specific information. Outcomes related to all stress, postpartum blues, mother‐infant attachment, and breastfeeding were assessed at baseline and after therapy (on average, 2 months after baseline assessment). Sample size calculation for the primary research question was performed based on a pilot study, which assessed pre‐ and post‐measurement stres and depression levels in postpartum participating in a mindfulness program similar to MBCT, specifcally CALM Pregnancy as focused on training in formal mindfulness and informal mindfulness practices. The CALM Pregnancy program both involve eight weekly 2.5‐hr sessions. Sessions included didactic presentations, group exercises, formal meditation practices, and leader‐facilitated group inquiry and discussion. Formal practices included the body scan, mindful yoga, and sitting meditation. Informal mindfulness practices included mindfulness of everyday activities such as mindful eating and mindful walking. The intervention also incorporated the 3‐min breathing space and cognitive approaches for developing alternative ways of responding to stress and anxiety symptoms. Given the similarities in the content, structure, and intensity of the two programs, the investigators used this pilot study for the sample size calculation. With a statistical power of 0.95 and an alpha of 0.05, 45 postpartum mothers patients were required per group (90 in total) to be able to detect diferences with an effect size of at least 0.50. [Türkiye]

Nct (2023). "Mobile Application-based Exercise Intervention for Pregnant Women." ClinicalTrails.gov.
	A mobile application (app) that can increase physical activity during and after pregnancy is novel, timely, and critically important to maternal health. Mobile phone‐based interventions show significant promise because they can be tailored to the target population, can be delivered at any place and at any time (with or without internet connection), are interactive, and are accessible to the majority of the population irrespective of socioeconomic status (96% of U.S. women ages 18‐49 own smartphones). The use of mHealth apps has been associated with behavior change, specifically adaptation of healthy lifestyle approaches. The majority of pregnant women report using an app related to pregnancy; it is the health condition with the highest number of apps available. However, high‐quality evidence‐based mobile apps that address physical activity specifically for pregnancy do not exist. The overarching goal of this randomized controlled clinical trial is to test the efficacy of the mHealth app for improving physical activity levels among pregnant and postpartum women in a rural setting. Secondary outcomes include weight status, dietary intake, glucose tolerance, blood pressure, and mental health. After contact is established and eligibility confirmed, participants (N=176) will undergo a screener, a baseline assessment, and then randomized to the mHealth intervention or the attention control group. All participants will have data collected at the following timepoints: baseline (13‐15 weeks pregnant), mid‐pregnancy (23‐25 weeks), late pregnancy (35‐37 weeks), and postpartum (6 and 12 weeks). [Of note, 12‐week interventions during pregnancy are customary and have been shown to elicit clinically meaningful changes in outcomes. The pilot study protocol was 12 weeks of pregnancy and 12 weeks postpartum.] The proposed RCT will add an additional timepoint in early pregnancy (13‐15 weeks), which will increase the length of the intervention to 39+ weeks. This will further enhance the likelihood of the intervention influencing behavior and outcomes. There will also be three check‐ins via telephone (two during pregnancy and one during postpartum upon medical clearance at 6 weeks) to aid with retention, as well as allow participants to ask any questions about the app (intervention) or the educational brochure (attention control). The 13‐15 week gestation time point was chosen because most women have had an initial prenatal appointment (to ensure viability) and the risk of miscarriage substantially reduced. The late pregnancy timepoint was selected as women tend to become the least active during late pregnancy. Six weeks postpartum was selected as this is when most women have their only postpartum clinical appointment (i.e. opportunity for objective clinical data extraction). The 12‐week time point is important for assessing behavior as women transition back into activity after medical clearance, which is important for long‐term sustained activity. After the baseline assessment (13‐15 weeks gestation), the women will be randomized to the intervention or attention control group. The intervention group will receive free access to the mobile app (BumptUp®). BumptUp® users will watch an introductory video on the app's features which reiterates the goal of the app: to reach the recommended 150 minutes per week of physical activity. The app contains evidence‐based workout information and education as well as several resources aimed at increasing physical activity and overcoming barriers for women during and after pregnancy. Each app feature is not only developed as the result of feedback from rural study participants, but is developed with a specific mechanism for behavior change in mind. The attention control group will undergo the exact same study protocol (parallel) and receive the same amount of interaction from the study team; however, participants will obtain an electronic evidence‐based educational brochure about physical activity and dietary intake during pregnancy instead of access to BumptUp®. o ensure the control group is a true attention control, the study team has paid careful attention to recommendations and will ensure that the control group receives the exact same amount of interpersonal interaction as intervention participants (same number of emails, phone calls, surveys, and face‐to‐face interactions). Instead of a tutorial on the app at the time of randomization, participants will have an educational session with the study team about the educational brochure. Data Collected at each timepoint: To assess the primary outcome of physical activity (Aim 1), participants will wear an Actigraph wGT3X‐BT Accelerometer (ActiGraph LLC,) on their wrist for seven consecutive days at each time point (Pregnancy: 13‐15 weeks, 23‐25 weeks, 35‐37 weeks, Postpartum: 6 and 12 weeks). Monitoring physical activity for one week at multiple time points is standard in exercise research. Actigraph provides an accurate and reliable way to assess overall physical activity levels. Wrist‐worn tri‐axel accelerometers are a valid measure of physical activity in pregnant women. Data will be collected for seven consecutive days at 30Hz. The accelerometer output will be sampled by a 12‐bit analog‐to‐digital converter. Categories of activity will be determined using the following cut points: Sedentary (0‐99counts/minute), light (100‐1951 counts/min), moderate (1952‐5724 counts/minute), and vigorous (≥5725 counts/min). The percentage of time spent sedentary as well as the amount of time spent participating in different categories of physical activity ranging from light to vigorous will be calculated. Non‐wear times will be excluded from the analyses. Women will be asked to wear the devices for seven consecutive days without removal. If removed, it must be documented it so the study team can be sure it does not interfere with the analyses. The study team has a successful history of compliance with these devices among pregnant women, including the pilot study for the present intervention. Devices will be dropped off with careful instructions for when/how to wear the device and when/how to remove it. Because many women in the study reside in rural areas, the accelerometer can be delivered by mail with a prepaid return envelope to increase compliance. Because all participants will receive prenatal care at one of two clinics, prenatal appointments will also be utilized to meet participants and deliver/pick up accelerometer devices. Physical activity will also be assessed subjectively using the Exercise Vital Sign survey‐a survey specifically designed to determine whether someone meets 150 minutes of physical activity per week (i.e. meets the recommendations from the ACOG). The same participants and study design will be followed for Aim 2. The outcomes of focus for this aim will be obstetric outcomes with clear links to maternal morbidity and mortality rates, including maternal weight status, glucose tolerance, blood pressure, and mental health. Medical data will be collected directly from patient charts in order to assess will be used to determine weight status, glucose tolerance, and blood pressure. Team members (Dr. Maire Blankenship and Dr. Leigh Lindsey) will pull data directly from the Graves Gilbert Clinic and Women's Health Specialist's electronic medical record systems. These data include height, weight, and blood pressure results at prenatal appointments that correspond to data collection time points (i.e., 12‐17 weeks, 23‐27 weeks (wider time ranges due to appointments still being monthly for many women during early‐to‐mid pregnancy), 35‐37 weeks, and 6‐weeks postpartum. All data at 12 weeks postpartum will be patient/participant self‐report as there are no routine postpartum visits at 12 weeks. Per standard‐of‐care clinical protocols, oral glucose tolerance testing occurs at 24‐28 weeks gestation and will be used to determine glucose tolerance. Extracted data will be used to determine the impact of the intervention on weight gain/retention, blood pressure, and glucose tolerance. T e study team has already been granted permission to collect these data (see letters of support) and has a history of success at collecting these assessments per the pilot project. To assess mental health, electronic surveys will be distributed at each time point. These include the Edinberg Postpartum Depression Questionnaire and the State‐Trait Anxiety Inventory. Maternal depression and anxiety play a significant role in maternal morbidity and mortality, and physical activity improves symptoms of both during and after pregnancy. Therefore, it is important to understand if the mHealth app improves mental health. Research clearly shows a need to assess both anxiety and depression during and after pregnancy, as anxiety tends to be more common and more often overlooked. Therefore, the State‐Trait Anxiety Inventory was chosen to measure anxiety. Further, it is exceedingly clear that exercise can assist with reducing anxiety. In order to assess the app's ability to improve dietary intakes, as well as account the possible confounding impact of dietary intake on weight status, the National Cancer Institute Multifactor (Diet) Screener will be provided as part of the electronic survey package. At each time point, surveys will be administered via Research Electronic Data Capture (REDCap). During the pilot, data were successfully collected, and exit interviews indicate an acceptable level of participant burden.

Nct (2023). "Modulation of Reproductive Microbiota by Ligilactobacillus Salivarius CECT5713." ClinicalTrails.gov.
	The objective of the project is to elucidate if the oral administration of Ligilactobacillus salivarius CECT5713 is capable of improving the rates of term pregnancies in couples with infertility problems of unknown cause. On the other hand, the project is aimed to detect microbiological, immunological and hormonal markers that allow the identification of couples in which the administration of the strain could be particularly effective. This is a randomized, double‐blind, parallel‐group controlled nutritional intervention study. The intervention (Ligilactobacillus salivarius CECT5713 or placebo) will be performed during the 6 months prior to the fertility treatment and during the first IVF cycle (estimated 1‐2 months). In case of pregnancy, the woman will continue the treatment until 12 weeks of gestation.

Nct (2023). "MOPEXE and RE in Treating Dysmenorrhea." ClinicalTrails.gov.
	Quantitative research methods were used in the study and it was a randomized type study. The sample of the study consisted of women between the ages of 18‐30 who volunteered to participate in the study, showed symptoms of dysmenorrhea and can be accessed online. The names of female participants who volunteered to participate in the study and met the inclusion criteria were written on papers and put in a bag. Papers will be randomly selected by the evaluator by drawing lots. Participants will be randomly divided into 3 groups: motor imagery focused pelvic floor exercise group, relaxation exercise group, and combined group. Among the participants who agreed to participate in the study, the sociodemographic and menstrual characteristics information form and the Visual Analogue Scale value of 5 and above on the day when the menstrual cycle is most severe were included in the study, and the McGill Pain Questionnaire‐Short Form, Menstruation Attitude Scale (MBI), Functional and Emotional Dysmenorrhea Scale (FEDS) they will be asked to fill in. After the groups are formed, video home exercise programs will be delivered online (whatsApp, mail, etc.) to the participants. Individuals will be asked to apply the created video home exercise program individually in their own environment. Before the participants start their exercise programs, exercise programs will be taught by online interview. You will be asked to do the exercises for 8 weeks, 3 days a week. After the 8‐week exercise program is over, the participants will be asked to fill in the McGill Pain Questionnaire‐ Short Form, Menstruation Attitude Scale (MBI), Functional and Emotional Dysmenorrhea Scale (FEDS) on the day when the menstrual pain is most severe. Pre‐ and post‐intervention data were statistically analyzed and compared.

Nct (2023). "Mother and Baby Yoga Study - Early Postnatal Yoga and Mental Health." ClinicalTrails.gov.
	The intended research is an eight‐week online programme incorporating gentle postnatal mother and baby yoga.The project will provide essential pilot data to help determine whether mother and baby yoga would be beneficial if offered as a regular service. To achieve this aim, the following study objectives will be addressed: 1. Identify possible links between participation a in programme of mother and baby yoga and maternal subjective experience with mental health 2. Verify whether mother and baby yoga can influence mothers feelings about the bond with their baby 3. Request feedback from the participants to examine the feasibility of running a similar larger study The outcome measures include mental health and feelings about bonding. The project will provide essential pilot data to help determine whether parent and baby yoga would be acceptable and beneficial if offered as a regular service. Pregnant women and new mothers have suffered negative mental health impacts of COVID‐19. An online course has been designed to mitigate anxieties associated with the pandemic, enabling women to follow the course in their own time within a safe environment. The mental health of women during and after pregnancy is of major concern to health professionals, families and society. 20% of women develop mental health problems during pregnancy or within a year of giving birth. Mental health is the third largest cause of direct maternal deaths during or within 42 days of pregnancy. Suicide is the leading cause of maternal death within a year of giving birth. Perinatal mental health problems in the UK cost £8.1 billion per year. The average cost to society of one case of perinatal depression is around £74,000, of which £23,000 relates to the mother and £51,000 relates to the impacts on the child. The cost of mental health to the public sector is five times more than the cost of improving mental health services. Improving outcomes for women will minimise the negative effects on the infant. NICE add that a woman's ability to provide nurturing depends on her own emotional well‐being. The charity Best Beginnings believes that all children regardless of income or background should have the best possible start in life, laying foundations for better future life chances. UNICEF Baby Friendly initiative encourages frequent touch and sensitive communication as this trigger's oxytocin, which facilities babies brain development. Postnatal mum and baby yoga are two distinct areas of therapy, but work well when practiced together. Current evidence supporting yoga in the perinatal period is limited and mostly focuses on pregnancy. Sheffield and Woods‐Giscombé call for more larger studies to validate and extend existing findings that demonstrate the potential of yoga for improving mental health for women and infants. A systematic review concluded Yoga‐based interventions may offer a promising potential intervention for maternal mental health and well‐being. However, due to the limited number of studies, and a lack of consistency in study design and measures, more high‐quality research is required to establish these effects, assess potential benefits on other aspects of maternal well‐being and explore potential benefits for outcomes relating to the infant.

Nct (2023). "MVA to Improve the Pregnancy Outcome in Aged Infertility Women With Assisted Reproductive Technology." ClinicalTrails.gov.
	After being informed about the study and potential risks, all participants will write the informed contents. This study is a randomized controlled study co compare different treatment methods on the embryo development. Sibling eggs were randomly divided into test group and control group. Specific method of randomization: all the eggs of each subject were distributed into two dishes (dish 1 and dish 2). If the oocyte number is odd, put the extra oocyte into dish 1. Using statistical software, the two dishes were randomly treated as test group and control group. Thus, a random allocation table was generated and a separate random envelope was made for each subject. The random envelope is kept and distributed by the relevant personnel who are not involved in the screening and treatment of subjects and are authorized by the researcher. Each selected subject must open the random envelope. The subjects were subjected to routine ovulation promotion, and then the acquired oocytes and cumulus cell complexes (COCs) were obtained and fertilized in vitro. The test group oocytes were cultured with MVA, while the control oocytes were cultured without MVA. Thus, half of the eggs from each elderly infertile patient were treated with MVA.

Nct (2023). "Nordic Randomized Trial on Laparoscopic Versus Vaginal Cerclage." ClinicalTrails.gov.
	Both vaginal and abdominal cerclages are procedures that have been used to prevent preterm birth for more than 50 years. However, only one previous study (MAVRIC, Shennan et al. 2020) has compared the two methods in a randomised trial. Other than evidence from the MAVRIC trial there is uncertainty whether an abdominal cerclage should be preferred over vaginal cerclage, and which women would benefit from it the most. NORACT is an open, multicenter, superiority, randomized controlled trial with the overall objective to compare laparoscopic versus vaginal cerclage in woman in whom the clinician has equipoise as to whether an elective vaginal or abdominal cerclage will be the best intervention to prevent preterm birth. Participants will be recruited pre‐pregnancy or in early pregnancy and randomised to vaginal or laparoscopic cerclage. If randomised to laparoscopic cerclage this will be inserted pre‐pregnancy or before 10+0 weeks of gestation. The vaginal cerclage will be inserted during pregnancy, before 16+0 weeks of gestation. A total sample of 188 participants will be included to detect a target difference of 15% in the primary outcome between the two groups. The two primary outcomes are delivery before 32+0 weeks of gestation and baby death. The study extends from sites in Denmark, Sweden, Norway, Finland, Iceland, and the United Kingdom.

Nct (2023). "The Norwegian World Health Organisation Labour Care Guide Trial (NORWEL)." ClinicalTrails.gov.
	A large robust trial investigating the effect of the LCG is needed to establish a foundation of knowledge on which the decision of implementing the LCG on a national level should be based. The Norwegian WHO LCG trial addresses the WHO research priority question: "What is the effect of the LCG on processes of care, health, well‐being and outcomes during labour and childbirth?". The trial will have a special focus on intrapartum caesarean section rates and experience of labour. The overall aim of the trial is to test the LCG in an unbiased population in a Norwegian setting. The project will conduct a nationwide randomized controlled trial (RCT) to test the effect on labour interventions and maternal and neonatal outcomes compared to the previous WHO partograph. The Norwegian WHO LCG trial will be conducted through three work packages: WP1 consists of a feasibility study to develop an electronic version of the LCG, and will test its validity and usability prior to the planned RCT. WP2 consists of a stepped wedge RCT to assess the effect of the LCG on labour interventions and maternal and neonatal outcomes. WP3 consists of a survey to investigate patient reported outcome through the childbirth experience questionnaire (CEQ). This is a stepped wedge multicenter cluster randomised non‐inferiority trial, to be conducted within the nationwide NORBIRTH network for clinical obstetric research. The hospitals will act as clusters and the women as individual participants. During the trial period all hospitals will use the WHO partograph and the LCG according to the trial protocol for all women with a planned vaginal delivery, these women constitute the trial population. Women who want to opt out will not be included in the analyses. Each hospital has established local research groups which are dedicated to implement the project. The included hospitals will consent to adhere to the protocol in the trial period and state that they have the capacity to participate both logistically and practically. Local coordinators will be appointed with the responsibility of monitoring the trial and secure a thorough documentation according to the protocol.

Nct (2023). "Online Intervention Based on Pain Neuroscience Education for Women With Pregnancy-related Lumbopelvic Pain." ClinicalTrails.gov.
	60‐70% of pregnant women suffer from pregnancy‐related lumbopelvic pain. Its multifactorial origin makes it difficult to establish an appropriate treatment for pain control. In the general population, patient education is the first line of treatment. For pregnant women with LBP, the guidelines are the same as for the general population. In fact, prenatal education programs specifically collect recommendations and educational strategies for managing this pain. Within educational strategies, education in the neuroscience of pain has gained special relevance in recent years due to its positive results in reducing pain in patients with low back pain. This type of education is based on reconceptualizing pain through teaching the neurobiological mechanisms that underlie the pain experience. Despite the beneficial effects shown in patients with low back pain, its use has not yet been explored, to our knowledge, in pregnant women with pregnancy‐related low back and pelvic pain.

Nct (2023). "Optimal Frequency Used in Transcutaneous Electrical Nerve Stimulation (TENS) for Treating Pelvic Pain in Adults." ClinicalTrails.gov.
	Adults ages 18‐90 years old who have first been given the standard of care therapy according to the AUA/EUA guidelines depending on their specific pain modality, first line treatments based on suspected etiology (for example pelvic floor physical therapy for high tone pelvic floor muscle dysfunction or amitriptyline for interstitial cystitis) without success will be defined as refractory. Participants who have plateaued on their response to current intervention strategies will be offered the TENS unit as an adjunct. Participation will be offered by mail or in person. If by mail, the investigators will send the consent with the letter and questionnaires asking participants to call or bring the material if they would like to enroll. If the investigators speak to the subject over the phone, the investigators will discuss the study as comprehensively as if they were in the clinic. This will include explaining the concept of the TENS unit, the study itself, and clarifying any questions the participant has. Subsequently if they are interested in the study, the investigators will ask them to sign the consent and return it to us via mail or email. Those whose pain symptomatology is above a threshold and who choose TENS therapy will be included in the study. The participants will be randomized into three groups of 25 participants each. The randomization will occur in blocks so that if the investigators need to terminate the study early there will be an equal number of participants in each group. The size of the blocks will also be kept secret for allocation concealment purposes. The randomization will be stratified by gender so that there is an equal number of participants from each gender in each group, reducing potential for gender as a confounding variable. Group 1 will be the low frequency set at 20 Hz. Group 2 will be the medium frequency set at 50 Hz. Group 3 will be the high frequency set 100 Hz. There is no sham group in this study as it has previously been found that posterior tibial TENS is effective and lasting. As such, all participants will be treated as a matter of routine medical care for pelvic pain. The investigators will use a fixed pulse width of 200 microseconds (uS), with continuous rather than biphasic stimulation. The investigators will aim to recruit 25 participants per group for a total of 75 participants. Study Procedures Screening Day 7/ Week 1 (in clinic or virtual): The first data points (Day 0) will take place in the clinic during the participant's routine visit or at the time of the participant's phone call seeking participation. If during a phone call seeking participation, this will be considered a study phone call, not a billable visit. The participant will fill out the VAS and GUPI. The participants will be taught how to fill out the pain assessment questionnaires (the VAS and GUPI, validated tools for measuring genitourinary pain and symptoms respectively). This can be done via paper to be brought into the office at their next checkup or via an emailed link through Qualtrics and uploaded to a spreadsheet in a protected AMC OneDrive. The baseline pain logs will be reviewed for sufficient severity of pain episodes and the participant will be randomized into the study if their pain is above the designated threshold: participants who record a pain scale of 4 or higher on any of the VAS scores or QOL score of 3 or higher on the GUPI question #9 will be eligible for the TENS study. The GUPI and VAS will be collected at this time; this will record the participant's pain 1 week prior to the study and will be considered Day 7/week 1. The week 1 of screening will be combined with the first week of baseline measurement (week 2) for a 2‐week lead‐in. Participants will be taught how to complete a usage log (stating if the TENS was used each day and for how long in minutes) and will be asked to repeat this weekly. Participants will complete an inventory (the Treatment Map) of treatments tried prior to the TENS, throughout the study, and at the end. Baseline Day 14/ Week 2: If the participant enr ls, they will be asked to continue logging pain (VAS and GUPI, on paper or via Qualtrics) for one week, with the week 1 screening and the week 2 baseline week totaling a 14‐day control period. The control period will represent data (2 weeks of VAS and GUPI) with only baseline treatments and no TENS unit. At week 2 (the end of the 2‐week baseline, in person), participants will hand in scores and be randomized to a frequency. They will be given a TENS unit and taught how to use the unit. Teaching will include positioning of electrodes, as well as what buttons they are allowed to manipulate. The TENS unit settings will be pre‐determined at the clinic and measures will be taken to ensure that the settings cannot be altered at home. The participant will be instructed not to open the TENS unit during the 2 treatment weeks of the study to ensure the settings are maintained. They will be instructed to continue only their baseline treatments. Settings: The TENS unit used is a Compass Health TENS 3000, 3 mode Analog Unit. The participants' TENS unit will be set at Normal Mode (N), a pulse width of 200 microseconds and an intensity to be determined in the office based upon when the participant feels sensitive to the TENS unit. Frequency (pulse rate) will be determined by randomization. The participant will place the electrodes along the posterior tibial nerve on the medial ankle with a ground on the inner arch, each day for 30 minutes for a total of 14 days at the time of day typically associated with the worst pain or at the first opportunity for rest after this time. Group 1 will be the low frequency group. This means that the TENS therapy will use a frequency of 20 Hz. Group 2 will be the medium frequency group. This means that the TENS therapy will use a frequency of 50 Hz. Group 3 will be the high frequency group. This means that the TENS therapy will use a frequency of 100 Hz. Participants will be provided the TENS unit, its manual, and enough patches to last the 2 weeks of the treatment period. Participants will be given a weekly usage log, weekly pain VAS and weekly GUPI questionnaire logs again for 2 weeks they are actively using the TENS, with the option of paper or Qualtrics. In this log, the rating of pain by VAS and GUPI, the rating of genitourinary symptoms by GUPI, duration of TENS therapy, usage for every day of the week and adverse reactions to the TENS unit (rash) will be recorded. Participants may be called during the 14‐day treatment period to keep on track, address any concerns, questions, or any adverse reactions to TENS therapy by the physician or research staff. Their phone numbers will be maintained in the master key associated with the deidentified database in the AMC Onedrive protected research file for this purpose. At 7 days and the end of the 14‐day treatment period the visit can be performed either virtually or in the office. The 7‐day visit will be considered purely a study visit and the 14 day visit a standard of care visit. The completed week 3 and 4 VAS and GUPI, treatment usage documents will be returned. The participants will also be asked the question "Will you continue using TENS therapy for your pelvic pain?" Any persistent issues will be addressed during these visits as well and further options discussed. For those who would like to continue the TENS unit, participants will be taught how to adjust settings and sites at home. Participants will be given repeat VAS and GUPI at 1, 2, and 3 months post‐initial phase and seen again at 3 months as part of standard care. Here the investigators will review logs of what frequency patterns they developed with TENS usage on their own, if any. In this time participants may increase or decrease the frequency of their device anywhere in the range of 2 Hz to 150 Hz to see which they prefer most in this part of the trial. Participants will also be allowed to adjust pulse width (30 to 260 uS), mode (B N M), time (continuous, 15, 30 minutes), and intensity (1 to 8, 10‐80mA) as desired. The only requests will be that they remove the device if a discomfort occurs and that they log their settings versus their response.

Nct (2023). "Pain Neuroscience Education and Biomedical Pain Education in Primary Dysmenorrhea." ClinicalTrails.gov.
	The aim of this study was to compare the effects of biomedical pain education and pain neuroscience education, in addition to routine exercise training, on menstrual pain parameters (pain severity and duration, analgesic use), menstrual stress, somatosensory function, pain catastrophizing, pain beliefs, anxiety/depressive symptom level and quality of life in healthy individuals with primary dysmenorrhea. The design of the study is parallel group, randomized study. The study sample consists of healthy individuals aged 18 years and older with primary dysmenorrhea symptoms. Individuals will be randomly assigned to one of the two research arms. In addition to the exercise training, which includes stretching and relaxation exercises routinely used in the field of physiotherapy and rehabilitation in primary dysmenorrhea, the patients in the first research arm will be given pain neuroscience education once a week for 2 weeks. In the second research arm, in addition to the exercise training that includes stretching and relaxation exercises routinely applied in the field of physiotherapy and rehabilitation in primary dysmenorrhea, biomedical pain education will be given once a week for 2 weeks. Participants will be evaluated in terms of descriptive measurements and outcome measures 3 times in total, before the applications, immediately after the end of the application period, and 3 months after the end of the applications. The primary outcome measurement parameter of the study was determined as the Visual Analog Scale (VAS) score, which is used to determine the severity of menstrual pain. Secondary outcome measures are menstrual stress level to be evaluated with the Menstrual Distress Questionnaire, somatosensory function status to be evaluated with the Central Sensitization Inventory, pain catastrophizing state to be evaluated with the Menstrual Pain Specific Pain Catastrophizing Scale, pain beliefs status to be assessed with the Pain Beliefs Questionnaire, anxiety/depressive symptom level to be evaluated with Depression Anxiety Stress Scales‐21 (DASS‐21), quality of life to be evaluated with World Health Organization Quality of Life Scale‐Short Form and perception of change to be evaluated by 5‐point likert scale. Sample size calculated by assuming a standard deviation of 1 with a minimum study power of 80% and predicting an equal distribution to the study arms; 19 individuals for the first research arm and 19 individuals for the second research arm, a total of 38 individuals were determined. The research will be terminated after all evaluations of all individuals participating in the study are completed, when the targeted sample size and power are reached. In the literature, there is no study comparing the effects of pain neuroscience education and biomedical pain education in primary dysmenorrhea, which is a problem that affects women's lives significantly. It is important to reveal the effects of different pain trainings for effective pain management in primary dysmenorrhea.

Nct (2023). "Paracervical Block Versus Transcervical Block in Outpatient Procedural Hysteroscopy." ClinicalTrails.gov.
	To assess the best anesthetic pathway to decrease pain during outpatient hysteroscopy, the investigators will perform a multicentric prospective randomized trial, single‐blinded, that compares two types of local anesthesia in outpatient procedural hysteroscopy: paracervical block, that is the actual gold‐standard, and transcervical instillation. The population studied will consist in adult women with indication of an outpatient surgical hysteroscopy (myomectomy or polypectomy). Every one of them will be invited to participate the day of their procedure. In the outpatient hysteroscopy clinic, the investigators will verify inclusion and exclusion criteria, explain the objectives of the study, collect data and obtain the patient's consent. The sample size is 242 patients (121 in each group). The study will be performed in two different centers: ‐ Integrated University Health Center and Social Services of the East of the Island of Montreal ‐ Integrated University Health Center and social services of the South Center of the Island of Montreal Right before each procedure the patients will be randomized through anonymous and alternized enveloppes that will be distributed in each center, to either receive paracervical or transcervical anesthesia before hysteroscopy. Each patient will receive a pre‐established dose of sedative before the procedure, according to their weight: Fentanyl 0,5 mcg/kg IV and Midazolam 0,02 mg/kg. The subsequent doses will be noted. Under sedation, with the patient in lithotomy position, a medium size speculum will be inserted. The vagina will be disinfected with chlorhexidine and the anterior lip of the cervix will be gripped with a Pozzi forceps. According to previous randomization, each patient will receive one of the following alternatives of local anesthesia: ‐ Group A: Paracervical 10cc Bupivacaine 1%, without epinephrine, at 0.5‐1 cm depth of the cervicovaginal junction at 5 and 7 o'clock positions (20cc in total). ‐ Group B: Transcervical (uterine) 10cc Bupivacaine 1% through the endocervix using an 17‐Gauge epidural catheter During the procedure (T1), the nurse will be in charge to fill the scale (to avoid bias). The patients will be given a Visual Analogue Scale (VAS) to fill 15 minutes after the procedure (before discharge), to assess pain. For each group the investigators will calculate the average rate of pain according to the Visual Analogue Scale during and immediately after the procedure (15 minutes). The investigators will subdivide each group into pre and postmenopausal women and into nulliparous and parous women and compare their Visual Analogue Scale as well. Statistical analysis will be performed to compare results.

Nct (2023). "Parenting Skills Group for Mothers With Postpartum Depression." ClinicalTrails.gov.
	The primary aims of this study are to 1) better understand the biological/genetic mechanisms and processes of behavior change in mothers and babies relating to oxytocin receptor gene methylation; 2) complete an outcome assessment of the efficacy of the COSP intervention using a tele‐health format, specifically in relation to treating maternal depression; 3) to better understand the mechanisms and processes of change in relation to maternal and infant co‐regulation achieved through the promotion of a secure attachment between mothers and their at‐risk infants, and to understand how these processes form a trajectory of behavioral outcomes in kindergarten. The COSP program lasts for 8 weeks and will be delivered via Zoom. Researchers will collect a variety of data including biological samples, self‐report questionnaires, developmental assessment, and direct observation to assess predictors and outcomes relating to participation in the COSP program. Data will be collected prior to starting COSP, half‐way through participation, after having completed the program, and at several timepoints following completion.

Nct (2023). "PATH Program for for Severely Frail or Cognitively Impaired Patients Scheduled for Cancer Surgery." ClinicalTrails.gov.
	At Nova Scotia Health Authority (NSHA), geriatric medicine colleagues developed a preoperative palliative and therapeutic harmonization (PATH) clinic with the following objectives: 1. Assess medical conditions, health trajectory, and baseline frailty. 2. Conduct an in‐depth discussion with the patient (or their substitute decision maker) to review medical conditions and how frailty stage impacts decision‐making about surgery. 3. Co‐develop a care plan, including ways to optimize health. The investigators have elaborated a single center randomized cohort trial for patients aged 75 and older, screened as severely frail or cognitively impaired scheduled for curative or palliative‐intent surgery for bronchopulmonary, oropharyngeal, orthopaedic, gynaecological, breast or gastrointestinal cancers. Patients enrolled in the trial will be randomized to standard of care preoperative assessment versus PATH geriatric care arm.

Nct (2023). "Pelvic Floor Rehabilitation Study (Beckenboden-Rehabilitationsstudie - BREST)." ClinicalTrails.gov.
	This study compares the effectiveness of standard care, pelvic floor muscle training or vaginal pessary for the treatment of postpartum urinary incontinence.

Nct (2023). "PelviSense, an Innovative, Non-invasive, Biofeedback Device for the Treatment of Stress Urinary Incontinence in Women." ClinicalTrails.gov.
	Background and purpose: Stress urinary incontinence (SUI) is a common condition among women, resulting in urine leakage during physical exertion, sneezing, or coughing. Due to the risks associated with surgical and pharmacological treatments, women with SUI often prefer conservative treatments, such as pelvic floor muscle (PFM) training (PFMT). PFMT has been shown to provide increased beneficial effects when combined with electromyography (EMG) biofeedback (referred to as conventional biofeedback [CB]) via intravaginal probe than when performed alone. However, the CB device applied in clinical practice is not preferred by women because it is invasive, and involves the insertion of a probe into the vagina, causing pain/ discomfort. Therefore, we developed the PelviSense, a non‐invasive biofeedback device paired with wearable EMG sensors for use as a PFMT adjunct. The proposed study aims to (1) investigate the efficacy of PelviSense‐assisted PFMT compared with unassisted PFMT on SUI in women, and (2) identify the mechanisms underlying the beneficial effects of PFMT for the treatment of SUI. Hypotheses: (1) women assigned to the PelviSense‐assisted PFMT group will report a greater reduction in the severity of urine loss compared with women assigned to the unassisted PFMT group; and (2) improvements in the severity of urine loss will be mediated by increased PFM strength, causing an increase in bladder neck elevation and a reduction in levator hiatus (LH) area during the Valsalva manoeuvre. Methods: A two‐arm, parallel‐group RCT will be conducted using 132 non‐pregnant women with SUI, aged 18‐60 years. The study participants will be randomised into two study groups: PelviSense‐assisted PFMT or unassisted PFMT. Women will be supervised in the performance of PelviSense‐assisted and unassisted PFMT on a 1:1 basis for 4 weeks and instructed to perform unsupervised home exercises for 24 weeks after the completion of supervised training. Recruitment. Potential participants will be recruited using a non‐probability convenience sampling technique through public and university campus advertising. Randomisation and blinding. An individual who will not be involved in study recruitment will randomly assign participants to one of the two study groups (PelviSense assisted PFMT or unassisted PFMT) at a 1:1 ratio. Another individual will assign treatments according to a computer‐generated random schedule in permuted blocks of two within age strata. The allocation sequence will be concealed using sealed, opaque, sequentially numbered envelopes containing the group name and a personal identification number. To eliminate expectation effects and biases, a research assistant (RA) will complete the assessment of primary outcomes, and intervention training and supervision at HK PolyU will be conducted by a physiotherapy research postgraduate (RPg) student. Raw data will be double entered into a spreadsheet by a student assistant. Data analysis will be completed in a blinded manner, with code names (Groups A and B) used for each group, and group identities will only be revealed after the analysis has been completed. Procedure and baseline assessment. Potential participants will be invited to an in‐person visit at HK PolyU. On the first day of contact, the participants will complete a screening questionnaire and a 1‐h pad test to determine eligibility. Written informed consent and body mass index (BMI) measurements will also be obtained. The 1‐h pad test, International Consultation on Incontinence Questionnaire, Short Form (ICIQ‐SF), the Incontinence Impact Questionnaire, Short Form (IIQ‐7), and the MOS will be used to establish baseline severity of urine loss, SUI symptoms severity, QoL, and PFM strength, respectively. Participants will undergo a transabdominal ultrasound (TAU) to measure baseline bladder neck elevation and LH area during a Valsalva manoeuvre (cough). Following baseline assessments, participants will select an envelope containing treatment allocation details. Outcome measures: The primary outc e will be the severity of urine loss, as measured using the one‐hour pad test. Secondary outcomes will include quality of life, SUI symptoms severity, and PFM strength, as measured using the incontinence impact questionnaire, short‐form, international consultation on incontinence questionnaire, short‐form, and modified Oxford scale, respectively. Mediator variables will include the following: bladder neck elevation and levator hiatus area. Outcomes and mediator variables will be assessed at baseline, 4, and 24 weeks. Statistical analysis: Treatment and mediation effects will be evaluated using analysis of covariance and the Hayes' PROCESS macro, respectively. Statistical analysis. Hypothesis 1: Treatment effects on both primary and secondary outcomes between T1, T2, and T3 and across the intervention groups will be evaluated using analysis of covariance (ANCOVA). Hypothesis 2: Mediation analyses will be conducted using the Hayes PROCESS SPSS macro (v2.13), Model 4.

Nct (2023). "PEMF vs Laser for Stress Urinary Incontinence." ClinicalTrails.gov.
	Stress urinary incontinence, or involuntary urine leakage during activities like coughing, laughing, or exercise, is a common condition that impacts quality of life for many women. Pelvic floor muscle training is often used to treat stress incontinence, but additional therapies may enhance outcomes. This randomized controlled trial will compare two physical therapy modalities, pulsed electromagnetic field (PEMF) therapy versus laser acupuncture, along with pelvic floor training for improving stress urinary incontinence in 60 adult women. The study will evaluate their effects on pelvic floor muscle strength, severity of urine leakage, and quality of life. We hypothesize that PEMF and laser acupuncture will both improve stress incontinence, but PEMF will be more effective based on greater pelvic floor stimulation. The study aims to provide evidence on these physical therapy options so that optimized treatment plans can be developed for women with stress urinary incontinence.

Nct (2023). "Phase 2 Study Evaluating the Efficacy of the Combination of DKN-01 (DKK1 Inhibitor, Leap Therapeutics) and Pembrolizumab in the Treatment of Advanced or Recurrent Endometrial Cancer." ClinicalTrails.gov.
	Primary Objective: ‐‐The primary objective is to determine the efficacy (objective response rate, ORR) of the combination of DKN‐01 and pembrolizumab in the treatment of women with advanced, recurrent endometrioid endometrial cancer or non‐endometrioid endometrial cancer with a Wnt/ β‐catenin activating mutation. Secondary Objective: ‐‐Estimate clinical benefit, progression‐free survival, overall survival, and duration of response in patients with recurrent or progressive EC treated with DKN‐01/ Pembrolizumab. To assess the tolerability of the combination. Exploratory Objective: ‐ We will perform the following translational studies to determine the correlation between molecular characteristics and likelihood of response to therapy. The six‐month progression free survival (PFS) and the median survival from time of study entry (first treatment) to progression (PFS) or death (OS) will be estimated. ‐ Determine if DKK1 over‐expression, using RNAscope in situ hybridization performed in a central lab, is associated with CTNNB1 mutation or mutation in other genes associated with Wnt/β‐catenin pathway activation. High expression of DKK1 is defined as greater than 10% positive cells on RNAscope. ‐ Determine if mutation status of CTNNB1 or other genes known to result in activation of WNT/β‐catenin signaling, such as RNF‐43, APC, AXIN1/2, RSPO2/3, and ZNRF3 [1], correlate to response to the combination in women with advanced or recurrent EC. Mutation status of these genes will be determined by next‐generation sequencing (Oncomine, ThermoFisher) in a CLIA‐ and CAP‐approved Molecular Diagnostics Laboratory in the Division of Pathology & Laboratory Medicine, MD Anderson Cancer Center using formalin‐fixed, paraffin‐embedded tissues OR other commercially available, CLIA‐certified platforms including but not limited to FoundationOne, Tempus, or CARIS. The presence of a mutation in any of these genes will be considered as indicative of Wnt/β‐catenin pathway activation in a patient's tumor. Mutation status will be correlated with treatment response. Mutation status will be correlated with tumoral DKK1 expression. NGS will be performed on baseline biopsies of metastatic disease at the time of enrollment, when available, or using the primary tumor from the hysterectomy if tissue cannot be obtained or is inadequate for testing. ‐ Determine optimal threshold of DKK1 expression and correlation to treatment response to DKN‐01 and pembrolizumab. ‐ Determine if IHC nuclear localization of mutant β‐catenin correlates to treatment response to DKN‐01 and pembrolizumab. ‐ Determine if IHC CD73 expression levels correlate to treatment response to DKN‐01 and pembrolizumab. ‐ Determine if PD‐L1 IHC levels correlate to treatment response. ‐ Determine if additional genetics by NGS including but not limited to PIK3CA mutations and TMB correlate to treatment response ‐ Determine if blood‐based protein markers including but not limited to cytokines at baseline and changes on treatment correlate to response

Nct (2023). "Phase I Trial Testing the Safety and Tolerability of Chemoradiation Followed by Chemotherapy + Dostarlimab for Stage IIIC, Node Positive, Endometrial Cancer." ClinicalTrails.gov.
	Primary Objectives: The primary objective of this study is to describe the safety and toxicity of chemoradiation with concurrent immunotherapy, followed by chemotherapy plus concurrent immunotherapy, followed by immunotherapy maintenence in patients with stage IIIC endometrial cancer. Secondary Objectives: The secondary objectives are listed below. ‐ To estimate progression free survival ‐ To describe the time to recurence and the recurrence patterns including extent and location (i.e. isolated versus multi‐focal, pelvic versus distant) ‐ To estimate disease specific survival and overall survival Exploratory: ‐ To determine if the presence of deficient mismatch repair (dMMR) or microsatellite instability correlates with progression free survival, disease free survival and 5‐year overall survival ‐ To assess patient reported outcomes (PROs) during the course of treatment and follow up

Nct (2023). "Physiotherapy in Stress Urinary Incontinence." ClinicalTrails.gov.
	The study was performed in the period of 07/21/2021‐30/10/2021. The study included 48 women 29‐49 years old who have complained of stress urinary incontinence for at least 4 weeks, who gave birth and signed the consent form. Women complaining of vaginismus, suffering from urinary tract infection, cancer, epilepsy or skin conditions with implanted pacemakers, metal implants and pregnant women were excluded from the study. Study participants were randomly divided into two groups: the I group (n=24), in which participants underwent functional magnetic stimulation (FMS) and the II group (n=24) in which subjects received pelvic floor muscle training (PFMT) program. Participants were evaluated before the intervention and repeated after 6 weeks. Subjects responded to a general questionnaire before the intervention, before and after the intervention, the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF) and Incontinence Impact Questionnaire‐Short Form (IIQ‐7) were used to assess the symptoms of urinary incontinence and their impact on quality of life. Pelvic floor muscle strength and endurance were assessed with a "Pelvexiser" perineometer. Statistical analysis was performed by IBM SPSS Statistics 26.0 and Microsoft Excel software 365.

Nct (2023). "PhytoSERM for Menopausal Hot Flashes and Sustained Brain Health." ClinicalTrails.gov.
	This is a double‐blinded, randomized, placebo‐controlled, parallel designed, proof‐of‐concept phase 2 clinical trial to determine effect of PhytoSERM on vasomotor symptoms and other symptoms associated with the menopausal transition. PhytoSERM or placebo pills will be administered orally once a day over 24 weeks. Safety and tolerability will also be assessed over the duration of the study. A total of 132 peri‐ or postmenopausal women aged 45‐60 years and who are experiencing hot flashes will be enrolled in this trial. To determine eligibility, all participants will undergo cognitive assessment, physical assessment, ECG, clinical/safety laboratory assessment, and interviews. After a 2‐week screening period, participants will be randomized to study intervention (PhytoSERM 50mg administered orally, once per day) or matching placebo, in a 1:1 allocation. After 12 weeks, participants in the placebo group will be crossed‐over to PhytoSERM 50 mg for the remaining 12 weeks (open‐label extension period). Hot flashes will be measured both objectively and subjectively. Objective data will be skin conductance levels collected via a wearable device that enables real‐time physiological data acquisition, including activity and sleep data. Study participants will be asked to complete a total of 8 study visits. Study visits will occur at 4‐week intervals after the baseline, except for visits # 6 and 7 (open‐label period) which will occur at 6‐week intervals after visit # 5 (final outcomes assessments visit). Visits 1, 2, 5 and 7 will last approximately 2‐4 hours; visits 3, 4, 6 and 8 will last approximately 45 minutes. All participants will be enrolled at a single site, at the University of Arizona (UA) Clinical & Translational Sciences Research Center (CATS).

Nct (2023). "PI4 - A Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia." ClinicalTrails.gov.
	Preeclampsia is globally responsible for 60,000 maternal deaths per year, and far greater numbers of fetal losses. Preterm preeclampsia is a severe variant with the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth (clinicians are forced to deliver the baby preterm for maternal or fetal health reasons). There is preclinical evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition. Previous research from the Preeclampsia Intervention 2 trial (PI2) show that metformin was able to delay delivery in early preterm preeclampsia. Metformin extended release (ER) was associated with a median 7.6‐day prolongation of pregnancy (geometric mean ratio (GMR) 1.39 (95% CI 0.99 to 1.96) P=0.057).Trends towards increased birthweight (mean difference 110gm (95%CI ‐80 to 300), a decreased length of stay at the neonatal intensive care unit (median difference 5.0 days less; GMR 0.86, 95% CI 0.62 to 1.2) and a shorter period of admission in any neonatal ward (median difference 12.0 days less; GMR 0.82, 95% CI 0.57 to 1.18) in the metformin ER group were found. Importantly, while gastrointestinal side effects were common, no serious adverse events related to trial medications were observed. The PI 2 trial has shown that metformin may be a disease modifying treatment for preterm preeclampsia. The trial is being repeated in a larger scale in the PI3 trial in South Africa to also assess neonatal outcomes. In Sweden, the demographics of the population are different and expectant management of preeclampsia allows for the women to reach 37 weeks of gestation as opposed to 34 weeks of gestation in the PI2 trial. This trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Swedish setting.

Nct (2023). "A Pilot RCT: the Impact of a Virtual MBSR Course on Women With Primary Infertility." ClinicalTrails.gov.
	We plan to perform a pilot study in which women with primary infertility seeking an initial fertility consultation will be randomized into either a standard treatment group or an 8‐week virtual Mindfulness‐Based Stress Reduction (MBSR) program. Primary outcomes included retention and survey completion rates. Secondary outcomes included Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Stress Score (PSS), Fertility Problem Index (FPI), pregnancy rates, intention to pursue treatment and % pursuing treatment.

Nct (2023). "Pilot Study of Mothers and Babies Online in Home Visiting." ClinicalTrails.gov.
	This pilot study examining how to incorporate Mothers and Babies Online or "eMB" into home visiting program workflows will have three Specific Aims: 1. Employ a user‐centered design (UCD) approach in which investigators will conduct semi‐structured qualitative interviews with key home visiting stakeholders (n = 10 parent clients, n = 5 home visitors) to generate recommendations on a) how to integrate eMB into home visiting program workflows, b) appropriate strategies for home visitors providing human support to support eMB engagement, c) reactions to the messaging and tone of eMB; and c) potential barriers and facilitators to eMB engagement. 2. Conduct a small randomized trial that examines the feasibility, acceptability, and effectiveness of eMB when implemented in home visiting programs. Investigators will recruit 50 pregnant individuals and new mothers from 5‐8 Parents as Teachers programs that serve rural communities. Investigators have chosen to focus on rural communities given the challenges associated with in‐person intervention delivery in those settings. These individuals will be randomized where 40 individuals will complete the eMB intervention and 10 will serve as controls receiving usual HV services. Participants who are at‐risk for developing postpartum depression will be eligible for the study. Investigators will assess risk for postpartum depression using two screening tools‐the Edinburgh Postnatal Depression Scale (EPDS) and the Postpartum Depression Predictors Inventory (PDPI). Women scoring in the mild/moderate range (5‐14) on the EPDS or scoring >3.5 on the PDPI are considered at elevated risk for postpartum depression. Data from the UCD phase will be used to develop study protocols for implementing eMB, including how home visitors providing human support/coaching while clients are engaged with eMB. Investigators will collect maternal self‐report data on depressive symptoms, perceived stress, and other mental health outcomes at baseline (pre‐intervention), 1‐week post‐intervention, and 3‐months post‐intervention. 3. Conduct brief semi‐structured interviews with n = 15 parent clients who received eMB during the pilot RCT and n = 5 home visitors who provided eMB coaching during the pilot RCT to understand user experience with eMB (with particular emphasis on understanding any human support/coaching component), which will guide any necessary modifications to the intervention protocol. Investigators will also conduct brief semi‐structured interviews with program managers from participating Parents as Teachers (PAT) programs and PAT leadership to assess organizational‐level barriers and facilitators to eMB uptake, which will inform future research directions related to the implementation of eMB.

Nct (2023). "Pilot: intraoperative TAP Block and Post-operative Pain Control for Minimally Invasive Hysterectomy for Endometrial Cancer." ClinicalTrails.gov.
	The investigators believe that the disappointing results thus far with TAP blocks in minimally invasive hysterectomy may relate to several factors. A combination of short and long‐acting anesthetic agents may provide the optimal analgesic effect. Large volumes of injection may promote spread of the anesthetics for better coverage, especially as long‐acting agents are known to diffuse minimally. Lastly, multiple injections may provide better coverage of the nerves that innervate the abdominal wall. The investigators also believe that laparoscopic TAP blocks, administered by the surgeon, have advantages over the more commonly used ultrasound‐guided approach typically performed by anesthesiologists. The laparoscopic approach is quick, on the order of a few minutes, whereas the ultrasound approach can be time‐consuming. There is also less risk of visceral injury since the injection is performed under direct laparoscopic view. There are now 2 randomized studies suggesting that the laparoscopic approach is equivalent to the ultrasound approach. An additional potential reason why most studies have been negative is that patients undergoing minimally invasive hysterectomy do not generally experience severe pain, making it more difficult to demonstrate pain reduction with any given intervention. However, the studies to date do indicate that these patients experience moderate pain and do use opiates. An intervention that markedly reduces or even eliminates opiate use would be of potential benefit. The investigators have used a TAP block technique that is performed intraoperatively by the surgeon under direct laparoscopic view. The investigators use a mixture of plain and liposomal bupivacaine injected at multiple sites and in large volume to distribute the drugs widely, potentially resulting in longer and improved efficacy. This method has not been previously studied in a randomized trial. The investigators propose to demonstrate that this technique markedly decreases opiate usage and pain scores in patients undergoing minimally invasive hysterectomy.

Nct (2023). "Postoperative Active Recovery." ClinicalTrails.gov.
	This is a randomized controlled trial comparing usual care postoperative restrictions and a novel new active recovery program to look at differences in pelvic floor function, patient quality of life, and mental health in between groups.

Nct (2023). "Post-operative Residual Voiding Volume Following Bulking and Vaginal Prolapse Surgery and Impact on In-hospital Stay." ClinicalTrails.gov.
	Project description Aim The primary aim of this study is to evaluate time to discharge in two different voiding trials techniques (strict vs minimalistic) after anterior, posterior or vaginal vault prolapse surgery as well as bulking surgery. Secondly, to evaluate the frequency of postoperative urinary tract infection, urine retention and pain as well as patients' calls to the gynecological ward after discharge. Hypothesis The hypothesis is that the intervention group (minimalistic trial) will have an earlier discharge and fewer complications compared to the other group (strict trial). Materials and methods The study will be performed as a two‐armed parallel randomized controlled trial. Relevant patients at Odense University Hospital will be informed about the study at the preoperative consultation. Prior to inclusion all women are provided with verbal and written information regarding the study protocol and they give their informed consent. All women will be randomized by a computer‐generated list in a ratio of 1:1 to either strict or minimalistic regime. Randomization is done using Redcap. An independent statistician generates the random allocation sequence. The study will be blinded for the operating doctor. Group A receives a strict voiding trial and group B receives a minimalistic voiding trial. In both groups the patient's catheter is removed at the operation room before returning to the gynecological ward. Group A is the control group and presents the current procedures with strict voiding trial. Here, the patient will postoperatively try to void approximately every second hour after catheter removal or if she has sensation of bladder filling. The bladder is scanned before voiding to determine the bladder volume, and the voiding volume is measured. If the voiding volume is >150 ml and the residual volume is <200 ml, the patient can be discharged. If the patient cannot fulfill the criteria at the first voiding, the patient voids again 1 hour later and so on. If the residual volume is above 300 ml intermittent catheterization will be placed and the voiding trial regime restarts. If no acceptable residual volume is reached, the patient will be instructed in intermittent catheterization and there will be a postoperative follow‐up the day after by telephone. If intermittent catheterization is not possible a closed catheter is placed which is opened approximately every third hour. The following day the patient will perform the voiding trial once again at the gynecological ward. Group B is the intervention group with minimalistic voiding trial. The patients in this group need to have one spontaneous voiding before discharge with the sensation of normal voiding, meaning there is no measurement of the voiding volume or residual volume. If the patients fail having spontaneous voiding or if the patients are in pain, the patients will undergo an ultrasound scanning to determine the bladder volume. If the patient's residual volume is above 400 ml the patient will be considered as failure and follow group A regime. If the patient's residual volume is under 400 ml the patient will continue group B regime and restart the regime. To determine the development of postoperative urinary tract infection, urine retention and gynecological pain, the patients will have to answer a questionnaire when included in the study and two postoperative questionnaires at two weeks and three months after surgery. These questionnaires will be sent to e‐box by using Open Redcap. To assess the patients' need for guidance after surgery, the patients' calls to the gynecological ward after discharge will be registered. Power calculation The sample size is calculated by means of medical‐statistics.dk and the test 'comparing two‐sample means'. Assuming the difference stated above, with a power of 80% we would need to allocate 84 patients (42 in each group) in the study. Estimating a drop‐out rate of 10% we aim to include 47 in each group. Inclusion criteria ‐ Women who undergo anterior, posterior or vaginal vault prolapse surgery or bu ing surgery at the departments of obstetric and gynecology, OUH. ‐ Women who have the catheter removed at the operating room. ‐ Women >18 years old. Exclusion criteria ‐ Any surgery performed by due to malignancy ‐ Previous cancer in the pelvic area ‐ Previous radiation therapy in the pelvic area ‐ Previous surgery in the pelvic area ‐ Patients not understanding Danish ‐ Patients with mental or similar illness ‐ Patients with multiple sclerosis or diabetes type 1 ‐ Patients with late KAD removal based on per operative assessment Statistical analysis Descriptive statistics In the study the baseline data and characteristics will be reported as means or numbers with 95% confidence intervals with a significance level set at an alpha of 0,05. Differences between groups will be evaluated by Chi square or Fisher's exact test. When appropriate, unadjusted odds ratio's with 95% confidence intervals will be calculated. Ethical consideration The study will be approved by Fortegnelse for Forskningsprojekter, Region of Southern Denmark. The study will be conducted according to the principles of the Declaration of Helsinki II.

Nct (2023). "Preemptive Analgesic Efficacy of Parecoxib for Reducing Postoperative Pain in Gynecological Surgery." ClinicalTrails.gov.
	The research is working on testing the preemptive analgesic efficacy of Parecoxib drug in gynecological surgery whether its can reduce postoperative pain score, reduce total opioid consumption in first 24 hour postoperation and reduce postoperation hospital length stay. Patients who are undergoing gynecological surgery is recruited to the research project while they admit in the hospital for preoperative preparation, in each type of surgery groups (1.Total abdominal hysterectomy 2. Adnexal surgery 3. Surgical staging) will divided in to 2 groups which is experimental group (Parecoxib) and control group (Normal saline). The experimental group will have Parecoxib administration 15 min before starting the surgery and control group will have normal saline administration 15 min before starting the surgery as same, the primary result is postoperative pain score which is interpreted by Visual analog scale index at 2,6,12,24 hour postoperation, the patients will get opioid drug (Morphine) for pain control depending on pain score index they inform, if pain score >7: morphine 0.075 mg/kg iv, if pain score 5 : morphine 0.05mg/kg iv, if pain score <5 : no morphine given. Lastly the side effect of Parecoxib drug will be observed and postoperative hospital length stay of each patient will be recorded

Nct (2023). "Pre-operative Polyethylene Glycol 3350 for Minimally Invasive Urogynecologic Surgery." ClinicalTrails.gov.
	The purpose of this study is to evaluate if there is a difference in bother related to constipation between a pre‐operative versus post‐operative start of a bowel regimen for patients undergoing surgery for pelvic organ prolapse This will be a multi‐institution, single‐blind, randomized control trial utilizing questionnaires and chart review to evaluate effect of pre‐operative bowel regimen on post‐operative constipation. 1. Study team and surgeons will be blinded to group assignments, participants will not be. 2. Participants will be randomized after consent is obtained, and at least 1 week prior to planned surgery, via computer‐generated blocks in a 1:1 ratio between study group (pre‐operative and post‐operative use) and control group (post‐operative only use) of polyethylene glycol 3350 (PEG)

Nct (2023). "Pre-Operative Prehabilitation Program Women With Gynecological Cancer." ClinicalTrails.gov.
	The aim of prehabilitation programs is to eliminate intraoperative complications by increasing the functional capacity and metabolic reserves of patients before surgical treatment and to accelerate recovery in the postoperative period. In addition, it helps the patient to maximize the existing capacity of the patient before the surgery, to know what will happen at each stage of the treatment to be applied to the patient, to feel better physically and spiritually and to understand the roles and responsibilities of the individual care of the patient, as well as making a significant contribution to the positive results of the operation. It is to provide exercise, psychological support, nutritional counseling and optimization of the underlying conditions by stopping negative health behaviors. There are non‐eliminable criteria such as age, gender, comorbid diseases before surgery, as well as modifiable factors such as the regulation of the patients nutrition, ensuring psychological well‐being, quitting smoking. In particular, some factors directly affect the state of well‐being during the perioperative period. Thus, surgeries become safer.As a practice, the prehabilitation program (according to the surgery program) is planned in the preoperative period between 2‐4 weeks Dec. Participants who do not comply with the program will be excluded from the sample

Nct (2023). "Preoperative Vaginal Dinoprostone Versus Misoprostone in Abdominal Myomectomy." ClinicalTrails.gov.
	Background; Myomectomy is a curative interventional option for many kinds of uterine fibroids, but considerable intraoperative haemorrhage and the necessities for transfusions of blood are still the main challenge for abdomen myomectomy. Aim and objectives; To compare the efficacy of preoperative administration of dinoprostone 20 mg versus 400 ug misoprostol vaginally in decreasing the amount of bleeding during abdominal myomectomy Subjects and methods; This was a prospective randomized double‐blind controlled study that included 90 patients complaining of uterine myoma and indicated for myomectomy selected from the outpatient clinic at Beni‐suef university hospital

Nct (2023). "Presacral Nerve Block Versus Sham Block on Post-operative Pain for Total Laparoscopic Hysterectomy." ClinicalTrails.gov.
	The proposed study is a single‐center parallel group RCT comparing the administration of a presacral nerve block using 20mL of local ropivacaine 5.0mg/ml versus 20mL of normal saline (sham block). This drug/dose was selected based on the recent study by Rapp et al. who instilled 20mL of ropivacaine into the presacral nerve at the time of open hysterectomy. Participants will be selected using a convenience sample from Mount Sinai Hospital's outpatient gynecology clinics. All patients > or = age 18 years undergoing total laparoscopic hysterectomy will be considered for this study. Exclusion criteria include: previous presacral neurectomy, concurrent surgical procedure other than salpingectomy and/or oophorectomy, gynecological cancer beyond stage 1 disease, chronic opioid consumption, fibromyalgia, BMI >50, language barrier, inability to communicate and inability to provide consent. All potentially eligible patients will be invited to participate in this study by their surgeon. Interested patients will then meet with a member of the research team to explain the study and obtain consent. The investigators will create a randomization list using a computer‐generated allocation sequence in equal ratio with study numbers 1 to 60. Our clinic nurse, who works 5 days per week in our ambulatory office and who will have no other role in this study, will prepare the active and placebo syringes and label the syringes according to the randomization list. Each syringe will be prepared individually and provided to the surgeon on the day of surgery. Study participants will be randomized on the day of surgery. The surgeon will instill the drug/placebo from the labeled syringe into the presacral space as the first step prior to starting the hysterectomy. The surgeon, research team, participants and data analysts will be blinded to treatment group. Each study patient will receive standardized perioperative care as follows: All patients will receive preoperative multimodal analgesia with acetaminophen 1000 mg. A protocolized general anesthetic will be used for all patients. Induction of anesthesia will be performed with fentanyl (1‐3 mcg/kg), propofol (2‐3 mg/kg), and rocuronium (0.6 mg/kg), followed by endotracheal intubation. Patients will be maintained with Sevoflurane anesthetic titrated to a minimum alveolar concentration (MAC) of 0.9‐1.2 in a mixture of 50:50 air/oxygen. Analgesia will be provided with intravenous fentanyl and/or hydromorphone administered to maintain mean arterial pressure or heart rate within 20% of baseline measurements. At skin closure, unless contraindicated, all patients will be administered intravenously ondansetron 4 mg and IV dexamethasone 0.1 mg/kg for nausea prophylaxis. Unless contraindicated, all patients will also receive intravenous ketorolac 30 mg for analgesia. Local anesthetic will be provided at the site of the port incisions (2ml per port site of 0.25% bupivacaine with epinephrine). Following completion of surgery, neuromuscular blockade will be antagonized with neostigmine and glycopyrrolate, and patients will be extubated and brought to the post anesthesia care unit (PACU). As per protocol and routine care, the only adjunctive analgesic administered intra‐operatively in addition to opioids will be intravenous ketorolac. Post‐operative pain scores will be assessed using a self‐administered numeric rating scale (NRS) for pain at 1, 2 and 3 hours after arrival in the PACU. Those patients with pain scores > 4/10 will receive analgesia according to a standard postoperative analgesic regimen. This will consist of intravenous fentanyl 25‐50 mcg boluses every 5‐10 minutes, intravenous administration of hydromorphone 0.2‐0.4 mg boluses as required, and oral administration of either hydromorphone IR 1‐2 mg or oxycodone IR 5‐10 mg. Rescue antiemetics will be administered if required at the discretion of the anesthesiologist in the form of IV metoclopramide 5‐10 mg, ondansetron 4 mg, or dimenhydrinate 25‐50 mg. Patients will be contacted post‐operatively days 1, 2 and 7 i rder to assess post‐operative pain scores, calculate total opioid consumption and elicit any adverse events (secondary outcomes).

Nct (2023). "Preventing Postpartum Depression in Immigrant Latinas." ClinicalTrails.gov.
	Postpartum depression (PPD)‐i.e., depression in the first postnatal year‐affects 10‐20% of women and is associated with diminished functioning, impaired interpersonal relationships, decreased parenting self‐efficacy and less responsive parenting. Immigrant Latinas living in the United States are disproportionately affected by PPD, with rates estimated between 30‐42%. Hypothesized mechanisms for this excess risk include acculturative stress, high rates of trauma, poverty, discrimination, and limited social support. Unfortunately, PPD prevention and treatment is limited among immigrant Latinas due to structural and cultural factors including lack of insurance, competing demands, shortages of language‐concordant providers, and stigma. These factors underscore not only the need for interventions to reach this population, but also the need to deliver interventions outside of traditional healthcare settings. Mothers and Babies (MB) is a group‐based cognitive‐behavioral intervention designed to teach mood regulation skills to women at risk for PPD. Originally developed for women of Latin American descent, the United States Preventive Services Task Force recognized MB as one of the two most effective counseling interventions for PPD prevention, with moderate to large effects sizes found across a series of randomized controlled trials (RCTs). MB has shown consistent positive effects when delivered to women across different racial/ethnic groups, including immigrant Latinas. However, prior MB trials with immigrant Latinas have found variability in dosage received, resulting in weaker intervention effects for individuals less fully engaging with the intervention. Previous MB trials also did not explicitly address social determinants of health such as food insecurity that may mitigate intervention effects. Immigrant Latinas have found the group modality highly effective in decreasing isolation and expanding access to resources and social networks, thus suggesting a potential larger role for group intervention modalities to address key social determinants of health. This R01 application builds on previous trials of the MB in‐person group intervention with immigrant Latinas by examining the effectiveness and implementation of virtual delivery of MB ("Mothers and Babies Virtual Group"; MB‐VG). No prior studies have examined the effectiveness of a virtual group‐based intervention to prevent PPD. Virtual interventions have the potential to mitigate structural barriers to receipt of mental health services commonly experienced by immigrant Latinas, thereby enabling increased intervention dosage. Virtual platforms can also facilitate delivery of multidisciplinary content by off‐site providers that address inter‐related social determinants of health that may moderate intervention impact. As such, the Investigators developed and pilot‐tested MB‐VG, modifying content of the in‐person MB group intervention for virtual delivery, incorporating content focused on social determinants of health and parenting delivered by external service providers, and incorporating text messages as an implementation strategy to reinforce intervention content and promote intervention engagement. Pilot testing with 30 immigrant Latinas enrolled in three family support centers (Judith P. Hoyer Early Learning Hubs, "Judy Centers") in Maryland demonstrated good feasibility and acceptability of MB‐VG. Investigators also found small to medium effect sizes demonstrating MB‐VG effectiveness in reducing depressive symptoms and parenting stress and improving self‐efficacy to manage emotions. The investigators are now poised to test MB‐VG in a rigorous RCT and propose to conduct a Type 1 Effectiveness‐Implementation RCT that enrolls 300 perinatal women (150 MB‐VG; 150 controls receiving usual family support services) from across 12 Judy Centers with the following Specific Aims: Aim 1: To examine MB‐VG effectiveness with perinatal immigrant Latinas at risk of PPD. Women receiving MB‐VG will exhibit greater reductions in depr sive symptoms (Hypothesis 1; H1), exhibit fewer cases of PPD (H2) and report increased parenting self‐efficacy and responsiveness (H3) compared to control participants receiving usual family support services. Exploratory Aim: Amongst enrolled participants (n 150) who have an older child aged 2.5‐4.5 years, the study will examine whether the skills taught in MB‐VG also promote less child dysregulation and greater child readiness for school. Aim 2. To evaluate MB‐VG implementation. To inform future intervention delivery and scalability, the study will assess key implementation outcomes. Guided by the RE‐AIM framework, mixed methods will be employed (e.g., semi‐structured interviews, survey data, and session audio‐recordings) to assess MB‐VG reach, adoption, implementation, and maintenance. Aim 3. To examine contextual factors influencing MB‐VG effectiveness and implementation. Guided by the Consolidated Framework for Implementation Research (CFIR), the study will measure contextual factors at the outer (e.g., participant needs/resources), inner (organizational characteristics), actors (facilitators), intervention and implementation process (virtual) levels via mixed methods.

Nct (2023). "Prevention and Treatment of CINV Caused by TC Regimen in Gynecological Malignant Tumor Patients." ClinicalTrails.gov.
	The risk of vomiting caused by high‐dose carboplatin is controversial, and there is currently no prevention of TC in patients with gynecological malignant tumors High‐level evidence‐based medical evidence for programme‐induced CINV. Therefore, different guidelines recommend the best antiemetic regimen as well It's different. This study is intended to conduct a prospective, multicenter, randomized, double‐blind, placebo‐controlled, crossover study The designed Phase III clinical study provides important data and basis for clinical practice and guideline formulation.

Nct (2023). "Progesterone Primed Ovarian Stimulation Protocol Versus Antagonist Protocol for PCO Patient." ClinicalTrails.gov.
	A Randomized controlled, non‐blinded study (parallel‐group study with 1:1 randomization) will be conducted at a Specialized Authorized IVF unit starting from January 2023 till completing the sample size. Randomization will be generated by a computer and held with one of the experimenters, and (n) of the black and red cards will be used for allocation concealment. Participants: All PCO patients will be given informed consent about the study aims and written consent will be taken at the first visit to the infertility clinic of the Specialized Authorized IVF unit. Patients will be categorized as (Group A) Progesterone primed ovarian stimulation protocol. (Group B) conventional antagonist protocol.

Nct (2023). "Progesterone Therapeutic Regimen Plus Statins in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia." ClinicalTrails.gov.
	After diagnosed of AEH or EEC by hysteroscopy, patients meet the study criteria will be enrolled. The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue was detected by Raman scattering instrument. And Age, height, weight, waistline, blood pressure, basic history of infertility and family cancer will be collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), blood lipids, sex hormone levels, anti‐müllerian hormone (AMH) and renal/liver function tests will be performed before treatment to evacuate their basic conditions. Each subject will receive body fat testing by Inbody 770. Patients with endometrial cancer who met the inclusion criteria were randomly divided into the control group and the experimental group in a 1:1 ratio according to the random numbers generated in advance. The administration regimen for the two groups was as follows: 1. Control group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg‐500mg/ day or Mirena +GnRHa 3.75mg subcutaneous injection monthly); 2. Trial group: progesterone regimen (oral medroxyprogesterone acetate tablet 250mg‐500mg/ day or Mirena +GnRHa3.75mg subcutaneous injection monthly) combined with statins (oral atorvastatin calcium tablet 20mg/ day; or rosuvastatin 5mg/ day; or pivastatin 2mg/ day); The specific selection of progesterone regimen was based on whether the patients had oral progesterone contraindications and if BMI≥28kg/m2 was not suitable for oral progesterone, Mirena +GnRHa regimen was selected. The choice of statin drugs is based on the results of the drug sensitivity test of the patient's tumor tissue, and the most sensitive one of the three drugs is selected. For patients remained SD after 9 months of treatment but refused hysterectomy, a multiple disciplinary discussion would be held for individual case, and alternative treatment would be given. Maintenance treatment will be recommended for patients with CR, and participants will be followed up for at least 1 year.

Nct (2023). "Progesterone-Primed Ovarian Simulation in Controlled-ovarian Simulation of Infertile PCOS Patients." ClinicalTrails.gov.
	The study evaluated the safety and efficacy of the progesterone‐primed ovarian stimulation (PPOS) coupled with gonadotropin (FSH) for infertile women with polycystic ovary syndrome (PCOS) who were assigned for ICSI and frozen blastocyst transfer. 200 infertile women were divided randomly into Group C, which received Cetrorelix injection (0.25 mg daily) on day‐6, and Group S, which received oral dydrogesterone (20 mg/day) on day‐2 of the menstrual cycle till the trigger day. All patients received an FSH injection of 225 IU daily from day‐2 till triggering day. ICSI was performed and day‐5 blastocysts underwent vitrification ultra‐rapid cryopreservation till being transferred. Outcomes included the ability of PPOS to suppress the premature luteinizing hormone (LH) surge and prevent the development of ovarian hyperstimulation syndrome (OHSS), the incidence of profound LH suppression, the number of retrieved M2 oocyte and fertilization, chemical and clinical pregnancy rates, and the miscarriage rate.

Nct (2023). "PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer." ClinicalTrails.gov.
	This research study is studying if there is a difference in frozen embryo transfer protocols used (modified natural versus programmed) after a failed first programmed FET cycle, defined as either a negative pregnancy test or a biochemical loss, as a possible treatment for people undergoing infertility treatment and in vitro fertilization (IVF). Participants will be randomized, in a 1:1 ratio, in their second FET transfer attempt to either another programmed protocol or a modified natural protocol. Once randomized, participants will undergo routine FET monitoring based on their randomization allocation, transfer procedure and pregnancy monitoring as applicable. Additional ultrasound images will be obtained prior to the transfer procedure to assess the stiffness or flexibility of the uterus, called shear wave elastography. A participant blood sample and infant buccal swab will be collected for future research studies.

Nct (2023). "Prolonged Progesterone to Prevent Preterm Birth From IVF - ET." ClinicalTrails.gov.
	Participant: 20‐40 years old, IVF fresh embryo transplantation, singleton pregnancy, blood/urine HCG (+) Control group: The administration of vaginal progesterone (90mg/d) began from positive HCG in blood/urine until 12 weeks of gestation. Regular delivery examinations were conducted, and cervical length was detected by B‐ultrasound at 12, 16, 20 and 24 weeks of gestation respectively, while fetal growth and development were monitored. Follow‐up was continued until the end of delivery. Trial group: The administration of vaginal progesterone (90mg/d) began from positive HCG in blood/urine until 24 weeks of gestation. Regular delivery examinations were conducted, and cervical length was detected by B‐ultrasound at 12, 16, 20 and 24 weeks of gestation respectively, while fetal growth and development were monitored. Follow‐up was continued until the end of delivery. Observation index: The gestational age of delivery, symptoms of preterm birth and gestational age, gestational age at preterm birth or abortion, fetal growth and development, neonatal outcomes, and drug‐related adverse reactions were recorded for each participant.

Nct (2023). "Prophylactic Antibiotic Administration for Bladder OnabotulinumtoxinA Injection." ClinicalTrails.gov.
	‐ After informed consent is obtained, urinalysis will be collected. Post‐void residual will also be assessed by bladder scan if not already documented in the electronic medical record in the prior three months. ‐ Patients with positive urinalysis and symptomatic for UTI will be excluded from the study. ‐ Patients will be randomized in a 1:1 ratio to one of two groups. ‐ Group 1 will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection. ‐ Group 2 will receive one dose of antibiotic prior to bladder onabotulinumtoxinA injection. ‐ The same antibiotic will be continued for 3 days of total antibiotic administration with additional doses prescribed to the patient's pharmacy. ‐ Bladder onabotulinumtoxinA injection and dosing will be completed based on the surgeon's standard technique and template. ‐ Bladder onabotulinumtoxinA injection will be completed by staff or fellows in the Female Pelvic Medicine and Reconstructive Surgery division of the Genitourinary and Kidney Institute. ‐ Patients will be followed for 4 weeks after the procedure. ‐ At 4 weeks study investigators will contact the patient by phone to evaluate for any UTIs or adverse events not previously reported by the patient during the study period. ‐ Chart review will occur at 4 weeks to assess for any unreported events. ‐ Other than this additional phone call, post‐operative patient management will not deviate from the standard of care. ‐ Patients will be instructed to report symptomatic UTIs, urinary retention, or any other adverse events related to onabotulinumtoxinA or antibiotic to investigators. ‐ Patients that report symptoms suggestive of a UTI will result in obtaining a urine culture. ‐ Symptomatic, culture proven UTIs will be treated with appropriate antibiotics per the current AUA guidelines. ‐ Symptoms suggestive of urinary retention, such as increased urinary frequency, voiding small amounts of urine, or feelings of incomplete bladder emptying, will result in obtaining a post void residual (PVR) and urinalysis. ‐ Patients will undergo teaching to perform self, clean intermittent catheterization of the bladder per the discretion of the operating surgeon. ‐ Any adverse reactions to the prescribed antibiotic will result in discontinuation of the antibiotic and managed according to the severity of the reaction. Antibiotic regimens: Allergy, prior urine culture resistance or another contraindication to first line antibiotic will result in the patient being prescribed second line antibiotic and so forth. First line: Group 1: trimethoprim / sulfamethoxazole 800/160 mg once pre‐procedure Group 2: trimethoprim / sulfamethoxazole 800/160 mg once pre‐procedure plus 800/160 mg every twelve hours for 6 total doses Second line: Group 1: cefalexin 500 mg once pre‐procedure Group 2: cefalexin 500 mg once pre‐procedure plus 500 mg every twelve hours for 6 total doses Third line: Group 1: nitrofurantoin 100 mg once pre‐procedure Group 2: nitrofurantoin 100 mg once pre‐procedure plus 100 mg every twelve hours for 6 total doses Fourth line: Group 1: ciprofloxacin 500 mg once pre‐procedure Group 2: ciprofloxacin 500 mg once pre‐procedure plus 500 mg every twelve hours for 6 total doses

Nct (2023). "Psychoeducation in Preventing Postpartum Depression According to Watson." ClinicalTrails.gov.
	The postpartum period is marked by significant changes in a woman's priorities, roles, and responsibilities. It is a stressful transition period in which physical and emotional difficulties are encountered. This stressful transition period can seriously affect women's mental health and psychosocial well‐being. can affect. Postpartum depression (PPD) is a common complication in women. PPD can develop in approximately one in seven women. In addition, PPD, maternal morbidity and is one of the leading causes of mortality. Preventive psychosocial and psychological practices are effective in reducing the incidence of PPD. Cognitive behavioral therapy, interpersonal psychotherapy, and psychoeducational interventions are among the applications. These interventions have traditionally been face‐to‐face, individual and group. format, by phone, online, with peer support, and by trained professionals. can be done. In the meta‐analysis results of the randomized controlled trial, psychosocial and psychological interventions It has been found to be effective in preventing PPD. prevalence of PPD 37 randomized and semi‐randomized controls evaluated the efficacy of preventive interventions in reducing In this study, it was found that depressive symptoms were significantly lower in the intervention group. Education given in the perinatal period; mother and family, physical, emotional and mental preparation, health development and by focusing on improved lifestyle behaviors. These trainings are It is of great importance in helping them learn about pregnancy, birth and parenthood. The application of midwifery and nursing care based on a model increases the success of the results. Some models in the field of health education, the formation of behaviors health education program to evaluate our explanation and its impact on a particular behavior. helps us run. Therefore, a model for the conceptual framework of knowledge about PPD selection is required. The selected model includes the predictive factors of behavioral changes and the impact on PPD. should explain its effects. Health in midwifery and nursing One of the most frequently used models in education and promotion is Watson's Theory of Human Care (IBT). This The model consists of the concepts of love, compassion, respect, trust and human, and includes the individual as a whole. provides an evaluative care. Watson's theory suggested that nurses use artistic, encourages the use of aesthetic, spiritual, empirical, political and ethical ways of knowing. their care reach a greater level of awareness of their various physical and non‐physical dimensions. Watson model for nursing practice, 10 important factors in his theory and supports the concept. These factors (10 Healing Processes) are defined as follows: 1. Humanitarian‐devotional value system: Adopting values such as humanitarianism and devotion, approach the individual with love and compassion. 2. Instilling faith‐hope, honoring the other: Positive health between nurse and patient facilitates promotion. 3. Sensitivity: Developing sensitivity towards oneself and others, through accepting others. is the recognition of self‐actualization. 4. Help‐trust relationship: Developing helping‐trusting human care relationship, interpersonal care and is essential for the expression of both positive and negative emotions in the nurse‐patient relationship. This is the person effective communication to express emotions and to acknowledge and perceive the emotions of others requires the use of skills. 5. Expression and acceptance of emotions: Encouraging the expression of positive and negative emotions and acceptance is defined as a risk‐taking experience for both the patient and the nurse. Nurse and the patient must be prepared for positive or negative feedback. 6. Systematic use of scientific problem solving method in decision making, Scientific contribution to nursing care The nursing process is used to bring a problem‐solving approach. 7. Enabling teaching and learning: Promoting interpersonal teaching‐learning, car nd treatment is an important distinguishing factor. This takes the responsibility from the nurse and puts it on the patient. This concept the nurse to provide the patient with the necessary information and then the responsibility of following up to the patient. focus on scrolling. 8. Establishing a suitable environment for recovery: Supportive, protective or corrective mental, physical, Providing the sociocultural and spiritual environment

Nct (2023). "PureWick™ France and U.S. At-Home Pilot Study." ClinicalTrails.gov.
	In this prospective, post‐market, multi‐site, open‐label, crossover trial, women with urinary incontinence requiring the use of diapers (changes complets (French term)) at night will be 1:1 randomized to a treatment sequence using two devices (PureWick™ System and Hollister® Female Urinary Pouch External Collection Device) and followed for approximately 10 weeks through 2 treatment phases. Approximately 30 female participants from 2 sites will be enrolled into the study. Those meeting eligibility criteria will be treated according to the treatment sequence assigned during randomization. Participants will view the standardized training video for the applicable product at the beginning of each treatment phase and have access to the Information for Use document (IFU) to review during each treatment phase. The total expected duration of subject participation is approximately 10 weeks. Participants will use the device assigned in treatment phase 1 overnight while sleeping for 4 weeks (28 days) before transitioning to the second assigned device in treatment phase 2. There will be a minimum washout period of 2 weeks (not to exceed 4 weeks) between treatment phases and a re‐screening of eligibility criteria before the second phase. In both treatment phases, participants will independently place and remove the FEC (female external catheter) or FUP (Female Urinary Pouch) after standardized teaching is completed on the first day of the treatment phase. The primary objectives are to evaluate safety (skin injury) and efficacy (capture rate). Safety will be assessed using the Draize Scale and efficacy will be measured based on daily urine capture rate. Health Care Providers (HCPs) will visit participants' homes daily to perform a skin assessment and collect urine measurements during the treatment phases. Participants will be withdrawn from the treatment phase if grade 4 is achieved in any category on the Draize skin irritation scale. The secondary objectives are to assess quality of life, tolerability, comfort and ease of use. Quality of life and comfort and ease of use will be measured using self‐reported changes in quality of life via the validated Nocturia Quality of Life (N‐Qol) tool and subjective evaluation of the therapy via participant survey, respectively. Tolerability will be measured by number of days of actual use of both devices, and discontinuation rate attributed to the device's discomfort or inconvenience.

Nct (2023). "QL Block in Laparoscopic Myomectomy." ClinicalTrails.gov.
	This study aims to determine the efficacy of a quadratus lumborum (QL) block in decreasing postoperative pain in patients undergoing myomectomy for uterine fibroids. A QL block is a temporary anesthetic injection in the quadratus lumborum muscle, a muscle in the lower back, that has been previously shown to significantly reduce postoperative pain levels in patients undergoing abdominal and pelvic surgery. Because of its demonstrated effects, the QL block is becoming a standard of anesthesia and surgical care. Since participants will be undergoing a myomectomy procedure, the investigators believe that participants may qualify to participate in this study. The investigators will be comparing patients who receive the QL block (in addition to standard anesthesia and postoperative pain care) with patients who do not receive the QL block (in addition to standard care). The participants will be randomly assigned to one of the two groups and may or may not actually receive the block.

Nct (2023). "A Randomised, Partly-blinded Investigation to Evaluate the Clinical Performance and Safety of pHyph in Adult Women With Bacterial Vaginosis Compared With an Untreated Control Group." ClinicalTrails.gov.
	This is a randomised, parallel group, partly blinded investigation to evaluate the clinical performance and safety of pHyph in adult women with bacterial vaginosis. Patients will be randomised to active treatment or no treatment (untreated controls) in a 1:1 ratio. The Investigators carrying out the gynaecological assessments will be blinded. Patients will not be blinded. The population of this investigation will consist of post‐menarchal, pre‐menopausal females 18 years or older seeking treatment for BV symptoms ("fishy smell", irritation and burning). Approximately 82‐92 patients will be recruited and randomised. BV will be diagnosed according to Amsel's criteria, defined as having at least 3 of the 4 criteria. Active treatment (from the start of the investigation) will be compared to no treatment at day 7 after screening (primary endpoint). Clinical cure rate on Day 7 is defined as the absence of all of the following 3 Amsel criteria: ‐ Thin, white, yellow, homogeneous discharge. ‐ Clue cells on microscopy (>20% of epithelial cells). ‐ Release of a "fishy odour", i.e., a positive "whiff test" when alkali (10% KOH solution) is added. Patients receiving rescue treatment before Day 7 will be considered as treatment failures. Patients in the "no treatment group" will receive pHyph as rescue treatment if they are not cured day 7. They will thereafter follow the same scheme as the patients starting with pHyph treatment. After the initial pHyph treatment, daily during 6 days, patients will continue with pHyph twice weekly until day 25 when an additional assessment will be performed. If the patients are cured, they will continue to receive pHyph as preventive treatment during 6 weeks and possible BV recurrences will be assessed.

Nct (2023). "An Randomized Double Blind Controlled Trial of niPGT-A in Women With RPL." ClinicalTrails.gov.
	Trial Objectives and Purpose The primary objective of this randomized double blind controlled trial is to compare the efficacy in embryo selection based on morphology alone versus morphology and niPGT‐A in women with RPL undergoing the first frozen embryo transfer. The secondary objectives are to evaluate the impact of eNK cells on the miscarriage and live birth rates and the prediction of live birth using spheroid/BAP‐EB attachment assay. Main hypotheses to be tested: 1. The embryo selection based on morphology and niPGT‐A for aneuploidy results in a higher live birth rate of IVF in women with RPL as compared with the control group based on morphology alone. 2. The embryo selection based on morphology and niPGT‐A for aneuploidy results in a lower miscarriage rate following IVF in women with RPL as compared with the control group based on morphology alone. 2. Trial Design This is a randomized double blind controlled trial. Eligible women will be recruited for the study and informed written consent will be obtained after counseling. Endometrial assessment All women will have an endometrial biopsy using a Pipelle sampler 7 days after luteinizing hormone surge (LH+7) prior to the month of having IVF. Part of the endometrial samples will be fixed in paraformaldehyde for immunohistochemical staining of endometrial uNK cells with CD56 antibody [26,27]. The other part of the endometrial samples will be used for epithelial and stromal cell isolation for spheroid/BAP‐EB attachment assay [28], to predict the embryo attachment rate in a laboratory setting. Due to ethical issues and practical difficulty, the use of human embryos for endometrial assessment is not feasible. BAP‐EB model [28] will be used as the embryo (blastocyst) surrogate in this study. BAP‐EB spheroid model are differentiated from human embryonic stem cells. The BAP‐EB after 72h of differentiation (BAP‐EB‐72h) have molecular signature of Day 7 trophectoderm cells of blastocysts [28]. In this study, BAP‐EB will be co‐cultured with primary endometrial epithelial cells and the attachment rate will be determined according to our established protocol. IVF protocol Women will undergo IVF with or without intracytoplasmic sperm injection (ICSI) as indicated. The women will receive ovarian stimulation using the progestin‐primed protocol [29] or the antagonist protocol. Ultrasound scanning will be arranged on day 2‐3 of menses for the antral follicle counts and to exclude the presence of ovarian cyst. Serum oestradiol and progesterone concentration will be checked and if they are basal, ovarian stimulation with gonadotropin injections (225‐300 IU daily depending on the antral follicle count) for 10‐12 day is given. Provera 10mg daily will be given from day 2‐3 to day of trigger in the progestin‐primed protocol to prevent premature LH surge while GnRH antagonist will be started on day 6 of ovarian stimulation to day of trigger. Regular ultrasound monitoring will be performed to monitor the growth of follicles. Adjustment of the gonadotropin dosage is corresponding to the number and size of follicles. When three follicles reach >17 mm in diameter, GnRH agonist (Decapeptyl 0.3mg) or human chorionic gonadotrophin (Ovidrel 0.25mg) will be administered. Oocyte retrieval will be scheduled 34‐36 hours after the HCG or agonist trigger under transvaginal ultrasound guidance. Normal fertilization will be assessed and confirmed by the presence of two pronuclei at 16‐18 h after insemination. All cleavage stage embryos will be grown individually to the blastocyst stage, usually day 5 or 6 after oocyte retrieval, in a monophasic medium. On Day 3, the culture medium will be replenished, and culture will be continued at 37oC and 6% CO2 in reduced oxygen tension (5%). No fresh transfer of blastocysts will be performed in the stimulated cycle. Grading of blastocyst by morphology Blastocysts are graded according to Gardner's classification (29). The blastocyst grading system assigns 3 separate quality scores to each blastocyst embryo, based on the o lowings: 1. Blastocyst development stage: expansion and hatching status 2. Inner cell mass score 3. Trophectoderm score Expansion grade Blastocyst development and stage status 1. Blastocoel cavity less than half the volume of the embryo 2. Blastocoel cavity more than half the volume of the embryo 3. Full blastocyst, cavity completely filling the embryo 4. Expanded blastocyst, cavity larger than the embryo, with thinning of the zona pellucida 5. Hatching out of the zona pellucida 6. Hatched out of the zona pellucida Inner cell mass grade Inner cell mass quality A Many cells, tightly packed B Several cells, loosely grouped C Very few cells Trophectoderm grade Trophectoderm quality A Many cells, forming a cohesive layer B Few cells, forming a loose epithelium C Very few large cells Blastocysts are cryopreserved at developmental stage with expansion score 3 or above. If a blastocyst does not reach expansion stage 3 on day 5, it will be assessed on day 6 whether it is suitable for cryopreservation. Blastocysts with either inner cell mass or trophectoderm scored as B or above are regarded as utilizable blastocysts. Each blastocyst will be frozen by vitrification individually and its SCM ( 8 µl) will be frozen at ‐800C separately and individually. The embryologist will prepare a sequence of blastocyst transfer based on the best morphology by Gardner's criteria. Then, on the day of blastocyst freezing, women will then be randomly assigned into two groups in 1:1 ratio using a randomization program by the laboratory staff in the PGT laboratory. 1. the intervention group using morphology and niPGT‐A and 2. the control group based on morphology alone. The women and clinicians will be blinded to the treatment groups they are assigned. Only the laboratory staff in the PGT laboratory will be aware of the group assignment. niPGT‐A of spent culture medium (SCM) In the intervention group, comprehensive chromosome screening using NGS will be performed according to the recommendations of the company in all SCM samples. In the control group, the measurement will be done retrospectively in those SCM samples of blastocysts that are replaced in the first transfer. All SCM samples will be saved for possible future research. A commercially available NI‐PGT kit (PG‐Seq Rapid Non‐Invasive PGT kit, PerkinElmer) will be used to analyse SCM samples. The protocol has been previously optimized with non‐invasive samples from 15 laboratories around the world. The kit follows a single tube workflow, two‐steps PCR to whole genome amplify the DNA in SCM and then attaches indexes and sequence‐specific adapters to template DNA, resulting in sequencing ready samples. After purification, concentration of each sample is adjusted into equal molar, pooled (96 samples) and then sequenced on a MiSeq system (Illumina) at 1x75 bp read length. On‐board secondary analysis was performed automatically by the MiSeq Reporter (Illumina) followed by PG‐Find Software (v 1.0, PerkinElmer). Reads aligning to anomalous, unstructured and highly repetitive sequences are filtered from the analysis. A target bin size of 1,000 kb is used, giving a minimum resolution of 10Mb. All genomic positions refer to the human genome build NCBI 37. According to the default setting of PG‐Find software, classification of aneuploidy is determined by CNV (copy umber variation) value. CNV value >2.7 is considered as gain while CNV value <1.3 is considered as loss. Sample will be concluded as non‐euploid when one or more of the chromosomes shows gain/loss. The niPGT‐A report of the SCM sample can be euploid, non‐euploid and non‐informative. It is used only to prioritize the sequence of embryo transfer. Blastocysts with non‐euploid result in the niPGT‐A report will not be discarded. Blinding The embryologist will grade the morphology of blastocysts according to Gardner's criteria stated above and enter the grading of blastocysts into an online database, which will be managed by an IT technician. The laboratory staff in the PGT laboratory will enter the PGT result in o a local database when the NIPGT results are available. The IT technician will collect the database from the PGT laboratory and enter it into the online software to compile the sequence of embryo transfer according to a pre‐determined algorithm which depends on the day of blastocyst development (day 5 better than day 6), blastocyst morphology and niPGT‐A result. The IT technician will issue the sequence of embryo transfer which does not contain information on the grading of the blastocyst and the NIPGT result to the embryologists in the IVF laboratory. Therefore, the subjects recruited, the clinicians and the embryologists will be blinded to the group allocation. Our preliminary results of niPGT‐A Preliminary results of the ongoing NIPGT‐A trial involved 1168 SCM. Media cultured in parallel but without contact with embryos were collected as controls (n=238). Amplification was successful in 1158 SCM (99.1%, 1158/1168) and 1141 SCM resulted in conclusive result (97.6%, 1141/1168). All controls showed no amplification. Frozen embryo transfer (FET) Blastocysts can be replaced in the subsequent natural, letrozole or hormonal replacement cycles, depending on whether the women have regular menstrual cycles or not. Only one blastocyst will be transferred each time. In the control group, blastocysts with the best quality morphology will be replaced first and the sequence of blastocyst transfer is decided prior to randomization. In the intervention group, blastocysts with the best morphology and euploid result will be replaced first as the sequence of blastocyst transfer will be modified after the niPGT‐A reports are available. Pregnancy A urine pregnancy test will be performed 14 days after the transfer. If the pregnancy test is positive, transvaginal ultrasound will be performed two weeks later to locate the pregnancy and confirm foetal viability and the number of fetuses. Subsequent management will be the same as other women with early pregnancy. They will be referred for antenatal care when the ongoing pregnancy is 8‐10 weeks. Follow‐up Written consent regarding retrieval of pregnancy and delivery data will be sought from the women at the time of study as in all patients coming for IVF for infertility. The women will be contacted after delivery by phone to retrieve the information of the pregnancy outcomes as a routine after IVF pregnancy. The outcome of the pregnancy (delivery, miscarriage), number of babies born, birth weights and obstetrics complications will be recorded. Women who fail to get pregnant in the first FET will be unblinded and an euploid embryo will be replaced if available. If no euploid embryo, the women can opt to undergo the second IVF cycle.

Nct (2023). "A Randomized, Controlled Study Evaluating the Efficacy of a Skincare Routine and Acne Supplement or a Skincare Routine Alone on Improving Acne and Other Symptoms of PMS." ClinicalTrails.gov.
	This study aims to evaluate the efficacy of the MINDBODYSKIN Hormonal Acne Supplement and a prescribed skincare routine of 6 products on facial acne and on symptoms of PMS, compared to a skincare routine of 6 products alone. This study will last for 24 weeks. The study will be conducted as a randomized, controlled trial in which participants will be split into two groups. Both will use the skincare routine, but one group will also take the MINDBODYSKIN supplement in combination with the skincare routine.

Nct (2023). "A Randomized-Controlled Trial to Examine the Effects of a Daily Probiotic Supplement on Common Symptoms of Menopause." ClinicalTrails.gov.
	Symptoms of menopause can significantly affect overall quality of life. It is hypothesized that probiotic supplements can reduce the severity of these symptoms. This 90‐day randomized controlled trial will examine the effects of the Provitalize Natural Menopause Probiotic on weight loss, waist circumference, sleep, and symptoms of menopause including hot flashes, night sweats, mood swings, anxiety, fatigue and brain fog. Participants will take either the test product or a placebo daily. All participants will complete study‐specific questionnaires and provide sleep data from their Fitbit at Baseline, Day 30, Day 60 and Day 90. At Baseline, Day 30, Day 60 and and Day 90, participants will also provide a bodyweight measurement and a waist circumference measurement.

Nct (2023). "REFRaME-O1: a Study to Investigate the Efficacy and Safety of Luveltamab Tazevibulin in Women With Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) Expressing FOLR1." ClinicalTrails.gov.
	This is a multicenter, international, open‐label, 2‐part Phase 2 study designed to assess the efficacy and safety of luveltamab tazevibulin in subjects with relapsed platinum‐resistant epithelial ovarian cancer expressing FOLR1. Part 1 will consist of 2 dosing cohorts (Cohort A and Cohort B), with subjects randomized 1:1. Part 1 will be used to optimize the dosing regimen. Part 2 will further evaluate the efficacy and safety of the selected dosing regimen. Luveltamab tazevibulin will be administered intravenously (IV) over a 1‐hour infusion time every 3 weeks.

Nct (2023). "Reiki & Premenstrual Syndrome & Quality of Life." ClinicalTrails.gov.
	Premenstrual syndrome is common as a number of cognitive and emotional symptoms that started about a week before menstruation and has negative effects on the quality of life of women. In this period, symptoms affecting the quality of life are often listed as pain, bloating, edema, appetite changes, weight gain, tenderness, fullness, fatigue, drowsiness, anxiety, depressive symptoms and crying. It is known that women resorted to various methods that are pharmacological or non‐pharmacological methods to deal with these symptoms in the premenstrual period. These methods vary from analgesic to hot application or traditional and complementary methods. Reiki is a healing energy that is not exactly included in traditional and complementary practices but has been revealed by research. In short, it is an energy therapy that balances the body and has no negative side effects. There are two types: Usui Reiki and Kundalini Reiki. From this point of view, it is planned to perform a triple blind, randomized and placebo controlled type in order to determine the effect of Kundalini reiki application on the symptoms of premenstrual syndrome. The study is planned to be carried out with Ege University Faculty of Nursing between June 2023 and July 2023. The universe of the study will consist of all students studying at the faculty in 2022‐2023. The first stage of the study, which is planned to be carried out in two stages, will be made of descriptive‐specific type to determine the students with premenstrual syndrome, no sample selection will not be selected and all the students who meet the criteria of inclusion in the research will be taken. In the second stage, intervention and placebo groups will be identified by randomization among students with premenstrual syndrome. In the Premenstrual periods, Reiki application will be held in the Premenstrual periods and no energy work will be applied to the placebo group. For the second stage, the adequacy of the number of samples will be decided by making power analysis during the study. Research data will be collected by face‐to‐face interview method using the individual promotion form, premenstrual syndrome scale and SF‐36 quality of life scale and SPSS 22.0 package program will be used in statistical data analysis. At the end of the study, although the effectiveness of reiki application against premenstrual symptoms in nursing students is determined, awareness will be created to be used as a applicable method for the development of premenstrual symptom management and quality of life if the result is effective.

Nct (2023). "Responsive Web-based Roadmap (InT-mAp) in Infertility Treatment." ClinicalTrails.gov.
	Infertility affects approximately 48 million couples and 186 million individuals globally, and it has biological, psychosocial, and economic problems in couples. It is a vital global reproductive health problem that has burdens and affects not only families but also society and the state. Studies indicate that many situations experienced during the infertility treatment process negatively affect the treatment results, and the anxiety of individuals receiving treatment, especially women, is high. The previous literature reports that during the infertility treatment process, women experience a decrease in their anxiety and self‐confidence about drug administration, they have doubts about the dose, administration, and time of drugs, and the rate of mistakes made regarding drug administration is too high to be ignored. Such cases may lead to cycle cancellations in infertility treatment, interrupting the treatment, adversely affecting the success of the treatment, and thus exposing the couple to more than one treatment trial. The interruption of the treatment with the cycle cancellation, the increase in the number of treatment attempts, the repetitions cause the woman to be exposed to a higher amount of drug, the cost to increase with each treatment trial, an increase in the economic burden of the couples, and an increase in the financial burden for the country. In addition to these physical and economic burdens, feelings such as anxiety, concern, hopelessness, and depression increase in couples, and they may eventually experience burnout. In order to improve the care of infertile individuals, it is clearly stated in the literature that couples need open communication channels with health care professionals, obtaining qualified information, instilling realistic hope, empowerment, accessibility of care services, and they have unmet and high‐quality care needs. The increase in the use and use of web‐based education services in the globalizing world gives us hope in providing a solution to this issue. This project was mainly designed to answer the question of "Is the responsive web‐based roadmap (InT‐mAp) developed in solving the problems encountered in drug administration, treatment success and reducing anxiety in infertile women treated with Assisted Reproductive Techniques (ART)?" With InT‐mAp, which investigators will develop using web‐based education technology, which is a distance education method in this age of technology; investigators aimed to reduce/reduce the margin of error in ART treatment‐drug practices, to contribute positively to the treatment process, and to reduce the social, economic and psychological burdens by reducing the anxiety level of individuals in this process. Besides, the InT‐mAp, which will be developed to meet individuals' education and counseling needs for general infertility issues and the treatment process, will reduce the workload of healthcare professionals working in this field and make a positive contribution to drug administration consultancy. With this study, investigators aimed to provide participants with time‐saving, individualized care, to reach the right information whenever they want, regardless of time and place, on every subject they need in the field of infertility. Investigators predict that sufficient follicle development, healthy oocytes and pregnancy can be achieved by creating awareness in infertile women and minimizing the conditions that may adversely affect the treatment process and results. Contributing to the health and economic indicators of the country by reducing cycle cancellations and reducing costs are among our important goals. The most important features that make the project unique are the absence of online support and a sensitive web‐based training platform, where the infertility treatment process in Turkey can be followed in detail by the users, and individualized care and training needs are met.

Nct (2023). "Retroperitoneal Tunneling Versus Dissection Technique During Sacrocolpopexy." ClinicalTrails.gov.
	Women with symptomatic, stage II to IV POP who plan RA SCP at UTMB Health will be approached to participate. Using the study protocol inclusion and exclusion criteria, patient's eligibility will be determined. All eligible subjects will provide the written informed consent before any research data is collected. All screening assessments will be completed at a preoperative, in‐person, clinic visit, and within 60 days of surgery. The subject will then undergo randomization to tunneling versus dissection technique during RA SCP with the total sample size of 40 female subjects (20 per group). Concomitant procedures for POP or urinary incontinence are permitted and will be based upon the operating surgeons' standard clinical practice and best clinical judgement. Subsequently, the subject will have postoperative follow up at 2 weeks, 6 weeks and 3 months

Nct (2023). "The Role of Granulocyte Colony Stimulating Factor in Embryo Transfer Outcomes." ClinicalTrails.gov.
	Please see uploaded study protocol.

Nct (2023). "The ROSE Scale-up Study: informing a Decision About ROSE as Universal PPD Prevention." ClinicalTrails.gov.
	In 2019, the US Preventive Services Task Force (USPSTF) issued a recommendation indicating that it is possible to prevent postpartum depression through counseling interventions. The Reach Out, Stand Strong, Essentials for New Mothers (ROSE) program was one of the two interventions mentioned by name serving as a basis for the recommendation. ROSE was tested in 4 randomized trials in community prenatal settings with racially/ethnically diverse low‐income adult pregnant women and prevented 50% postpartum depression (PPD) cases. ROSE is scalable in that: (1) it does not require mental health clinicians or licensed providers of any kind; (2) it has a flexible delivery structure (e.g., group vs. individual, timing during pregnancy); (3) it is the shorter (5 vs. 8‐17 sessions) of the two interventions described in the USPSTF report. PIs Johnson and Zlotnick (the developer of ROSE) are in Year 4 of an implementation trial examining how much technical support is needed for various kinds of agencies to implement and sustain ROSE over time (R01 MH114883). That trial enrolled 98 agencies serving low income women nationally (i.e., settings where women receive perinatal care), including prenatal clinics, home visiting, Healthy Start, and doula groups, among others. It answers many of the questions posed in this RFA, including identifying: (1) a "service‐ready efficacious preventive intervention" that is "scalable and can be delivered with fidelity by setting providers;" (2) "strategies to train providers and support delivery of evidence‐based approaches with fidelity across health care and community settings;" (3) implementation barriers and facilitators; and (4) effective implementation strategies. However, that trial raised a question about the USPSTF recommendation. Universal vs. selective or indicated prevention. All effectiveness trials of ROSE and of the other recommended PPD prevention intervention included only low‐income women, a single risk factor that doubles incidence of PPD. Three of the 4 ROSE trials included women who were screened for additional risk for PPD per the Cooper survey to maximize trial power. Because the existing evidence base consisted of women at increased risk for PPD, the USPSTF recommendation suggested that "clinicians provide or refer… persons who are at increased risk of perinatal depression to counseling interventions," and called for "more studies on the use of tools for risk assessment." However, most of the healthcare and community agencies in our implementation trial (78%) provide or offer ROSE to every woman as part of their standard work flow (i.e., provide it as universal prevention), finding this more feasible than creating a screening and referral process for indicated or selective prevention. Most of the other agencies use provider judgment to refer to ROSE. Only 7% use a screening tool (typically the Edinburgh) for ROSE referral. In addition to being more feasible, universal prevention may be better because: (1) the cost of a screening false negative (resulting in a preventable case of PPD; $32,000) far exceeds the cost of ROSE delivery ($50‐300/woman); (2) women who already face societal stigma (racial/ethnic minorities, undocumented) can be fearful about consequences and feel further stigmatized when a screener singles them out as needing PPD prevention. This project assesses effectiveness, cost‐outcome, equity, and scalability of using ROSE as universal vs. selective or indicated prevention for PPD using commonly available/existing screening tools. We expect universal prevention to be optimal. Effectiveness of ROSE among low‐income women at risk for PPD is known (ROSE prevents 50% of PPD cases). To inform a recommendation about using ROSE as universal vs. selective or indicated prevention, we need to determine the effectiveness of ROSE among all pregnant persons, including those screening negative for PPD risk (defined in various ways; Section A6). We will enroll 2,320 people receiving prenatal care in a large regional health system (based in Detroit, MI), asse them with PPD risk tools (chosen for ease of use, wide use, or availability in electronic health records), randomize everyone to ROSE or to enhanced care as usual (ECAU), and collect information needed to inform a decision about ROSE as universal PPD prevention. Each proposed aim gathers a piece of information missing in the USPSTF report to guide decision‐making. We will assess ROSE as universal, selective, and indicated prevention in terms of: 1. ROSE effectiveness relative to ECAU for each prevention approach for (i) SCID5 major depressive episode (primary) and (ii) functioning in the 6 months after birth. We will explore effects between baseline and birth. 2. Cost‐outcome comparison of universal vs. selective or indicated prevention in terms of PPD and functioning. Because it prevents costly false negatives, universal prevention is almost always cost‐beneficial. 3. Equity: (a) Percent false negative screens for minority vs. non‐Hispanic white women; (b) minority status as a moderator of outcome across risk levels; (c) PPD cases that would be prevented by ROSE as universal prevention that would not be prevented under selective/indicated for minority vs. non‐Hispanic white women. 4. Scalability as indicated by: (a) cost‐outcome comparison of universal vs. indicated prevention (Aim 2); (b) a scalability measure and qualitative interviews with the 98 agencies in the past ROSE implementation trial about how they decided on universal vs. some other kind of prevention and how it went in their settings. 5. Mechanisms of ROSE effects across PPD risk levels. We will integrate results to advise about ROSE as universal prevention. This study fits the RFA by assessing how best to get an evidence‐based program to those who need it in settings where they receive perinatal care, by addressing a pragmatic and novel question (should ROSE be universal prevention?), and by examining equity. B. Innovation B1. This will be the first fully‐powered RCT to assess universal vs. selective or indicated prevention of an evidence‐based intervention for PPD in terms of prevention of PPD cases. The USPSTF recommendation on prevention of postpartum depression (i.e., that "clinicians provide or refer pregnant and postpartum women who are at increased risk of perinatal depression to counseling interventions") is new (2019) and was limited to women at elevated risk for PPD because that is what the evidence to date consisted of (i.e., trials among women at elevated risk for PPD). However, our current 98‐agency implementation trial and other factors suggest that universal prevention may be more scalable, cost‐effective, and equitable than selective or indicated prevention for PPD. This trial will be the first to examine the advisability of universal vs. selective or indicated PPD prevention (a) at all, & (b) with respect to equity, scalability, and comparative cost. B2. This definitive trial will be the largest PPD prevention trial to date. Among other advantages, this provides better power than previous studies to examine race/ethnicity by intervention interactions. B3. This trial will be the first to explore ROSE as antenatal depression (AD) prevention. B4. EPDS as a predictor of future PPD. The EPDS is a well‐validated and almost ubiquitously used measure of perinatal depressive symptoms and it makes sense that elevated symptoms likely predict future disorder. However, no previous study has ever tested the EPDS as a predictor of future development of full PPD (only its correlation with current disorder), despite being used this way in clinical practice. A bonus additional feature of this trial is that we can use the control condition (n 1,160) to evaluate the predictive validity of this commonly used measure. Currently, no AD symptom measure has been validated as a predictor of PPD. B5. Scalability is a relatively understudied area of implementation science. This study will provide the first (quantitative and qualitative) analysis of scalability of universal, selective, and indicated PPD prevention. Approach: Research Design h s project informs use of ROSE as universal vs. selective or indicated prevention for PPD by assessing: (1) ROSE effectiveness for each prevention approach among 2,320 women in terms of (i) SCID5 major depressive episode in the 6 months after birth (primary), and (ii) functioning. (2) Cost‐outcome comparison of universal vs. selective or indicated prevention in terms of PPD and functioning (equation in Section D2.11). Savings from preventing false negatives (PPD cases among "low risk" women) drives this comparison. (3) Equity: (a) percent false negative screens for minority vs. non‐Hispanic white women; (b) minority status as a moderator of outcome across risk levels; (c) PPD cases that would be prevented by ROSE as universal prevention that would not be prevented under selective/indicated for minority vs. non‐Hispanic white women. (4) Scalability of universal vs. other kinds of prevention as indicated by: (a) cost‐outcome analyses (Aim 2); (b) a scalability measure and qualitative interviews with the 98 agencies in the ROSE implementation trial. (5) Mechanisms of ROSE effects across PPD risk levels.

Nct (2023). "SBRT Alone or Followed by Niraparib for Oligometastases or Oligoprogression in Ovarian Cancer Following PARPi Therapy." ClinicalTrails.gov.
	Oligometastases or oligoprogression of ovarian cancer while on a PARPi may occur due to a secondary sub‐clonal mutation causing acquired resistance in a small volume of tumour rather than having global tumour resistance. Eradication of the resistant disease with stereotactic radiotherapy (SBRT) would enable continuation of the PARPi to maintain control of disease that has retained drug sensitivity and this has the potential to impact disease outcomes. For the purposes of this ovarian cancer trial, oligoprogression refers to the situation whereby 3 or less lesions of disease show evidence of progression. If there were previously other sites of disease, these remain in response or stable. Oligometastatic disease refers to the situation whereby complete response to treatment has been obtained and the disease relapse occurs that is limited in number and distribution (≤3 metastatic/recurrent lesions). SOPRANO will explore whether there is activity of SBRT and SBRT followed by niraparib in the case of oligometastatic or oligoprogression disease post prior PARPi in recurrent ovarian cancer. The trial will recruit patients with oligometastic or oligoprogressive ovarian cancer (≤3 sites/lesions) who have progressed on or following at least 6 months of treatment with PARP Inhibitor (PARPi). Patients will be randomised to one of two parallel non‐comparative treatment cohorts: ‐ Cohort 1: SBRT followed by niraparib ‐ Cohort 2: SBRT alone In both cohorts, therapy will continue until disease progression deemed by the investigator to warrant a change in treatment, unacceptable toxicity, withdrawal of consent or if the investigator decides it is not in the best interest of the patient to continue. Adverse events, including toxicity from trial treatment will be collected and graded according to The National Cancer Institute (NCI) Common Terminology Criteria (CTC) Version 5.0 (http://ctep.cancer.gov/reporting/ctc.html). Participants will be asked to consent for future linkage with routinely collected health data via national registries to trace their eventual vital status and assess subsequent unexpected comorbidities. Assessment of disease by RECIST will be required 8 weekly following completion of SBRT for the first year and 12 weekly thereafter until disease progression meeting the primary endpoint.

Nct (2023). "SGLT2 Inhibitors in Treating Patients With PCOS." ClinicalTrails.gov.
	This clinical study is a prospective, single‐center, randomized (1:1) controlled clinical study. The enrollment population is overweight or obese PCOS patients. After signing the informed consent form, patients who meet the inclusion/exclusion criteria will be randomly assigned to the experimental and control groups for treatment in a 1:1 ratio, for a total of 72 patients enrolled. Subjects randomized to the trial group will receive SGLT‐2 inhibitors plus metformin for 12 weeks. Participants randomised to control will receive placebo plus metformin for 12 weeks.

Nct (2023). "Single-port Versus Multi-port Laparoscopic Surgery for Ectopic Pregnancy." ClinicalTrails.gov.
	Single‐port laparoscopic surgery has become one of the treatment options for ectopic pregnancy with certain advantages such as reduced numbers of incision and scars, and increased patient's satisfaction post‐surgery. At Hung Vuong hospital, the investigators do not have data about the application potential of single‐port laparoscopic surgery for ectopic pregnancy treatment. Therefore, the investigators carry out this project to compare the effectiveness and safety of single‐port versus traditional multi‐port laparoscopic surgery in the treatment of ectopic pregnancy.

Nct (2023). "Social Media Navigation Aid Kits for Urinary Incontinence." ClinicalTrails.gov.
	The objective of this research is to perform a non‐masked, superiority randomized controlled trial to assess urinary incontinence (UI) symptoms of women newly diagnosed with UI before and after conservative treatment with either a Urogynecology Social Media Navigation Aid Kit or routine counseling. The target population are treatment naïve patients with urinary incontinence who are seeking care as a new patient. Our central hypothesis is that the addition of a Urogynecology Social Media Navigation Aid Kit will be superior to routine counseling alone in women with urinary incontinence. The investigators will recruit women with any type of urinary incontinence who present to the University of New Mexico Urogynecology practice at UNM Eubank Clinic (UNM) or Sandoval Regional Medical Center (SRMC). To confirm diagnosis and eligibility, The investigators will conduct a standard intake history and physical, complete with cough stress test, POP‐Q pelvic examination, urinalysis, and urine culture. All potential participants will receive routine counseling about possible treatment options appropriate for her urinary incontinence, regardless of group assignment. Their follow up appointments will be the same regardless of participation in the study. The intervention is a Social media Navigation Aid Kit (SNAK) which was created by using search terms, "urinary incontinence", "urinary leakage", and "urogynecology", and querying various websites/blogs, Facebook, Instagram, and YouTube. These social media platforms were chosen based on the top three social media platforms used in Americans aged 50 to >65 years old according to Pew Research Analytics (Pew paper). The experienced reviewer evaluated each platform for users that provided relevant, accurate, and specific content. The department of Urogynecology at UNM independently reviewed the curated pages and users for approval. Once approved, the various users and pages were then collected and an infographic was created. The infographic will be available via hardcopy (as a trifold), email, text, and/or via QR code per patient preference. Potential subjects will be recruited in the UNM Eubank and SRMC clinics when they present for care for OAB/UUI, either in person or virtually via telephone or Zoom care visits. All patients will have a history and physical taken to determine their study eligibility. Recruitment will take place either in private exam rooms at these clinics or over HIPAA‐compliant telephone or Zoom conversation. After recruitment, they will undergo the informed consent via the same means as recruitment and complete initial questionnaires in clinic or will be sent a copy (digital or mail) to read if enrolled virtually. The randomization sequence will be generated by computer‐based randomization in a sequence that preserves 1:1 randomization and also preserves allocation concealment (likely with randomly alternating block sizes of 6‐10 in blocked randomization). Randomization assignments will be completed via REDCAP by a research coordinator. Randomization will only occur after consent has been signed and all baseline data has been obtained. This is a single‐center study at the University of New Mexico, and this site will recruit up to 75 patients. Outcomes collected: Data will be collected prospectively using a series of surveys. Our primary aim is to determine whether the participants have improved self‐efficacy following the intervention based on the PROMIS Self‐Efficacy for Managing Symptoms questionnaire at 3 months. The target population will be patients with urinary incontinence who are seeking care. If a patient is interested in this and fulfills study inclusion criteria then The investigators will offer her the choice of volunteering for the study. All women will give consent prior to their enrollment, after they have had time to carefully consider whether they want to participate in the study. Research staff and clinicians will obtain consent either in clinic or via zoom. After enrollment, participants will fill out baseline surveys including ncontinence Severity Index (ISI), Patient‐Reported Outcomes Measurement Information System for Managing Chronic Conditions‐ Managing Symptoms (PROMIS‐SE‐MCC‐MS), Incontinence Impact Questionnaire (IIQ‐7‐SF). At 3 months, patients will fill out the following surveys: ISI, PROMIS‐SE‐MCC‐MS, PGI‐I, IIQ‐7‐SF, and 3‐month follow up questionnaire. If unable to contact the patient 3 times, The investigators will discontinue attempts and the patient will be considered lost to follow up. Data Analysis: Power analysis was performed based on previously reported minimally important change (MIC) of 2‐6 points for PROMIS measures (26). The investigators will use the MIC of 2 points, divided by the expected SD of 10 points, giving us an effect size of 0.2. In order to examine the extent to which the score improves depending on the study arm assignment, repeated‐measures ANOVA was used. To achieve significance for a non‐inferiority study using these assumptions the investigators would need 50 patients, 25 per group to detect this difference with alpha =0.05 and with 80% power. To allow for a dropout of 20% the investigators will enroll at least 50 patients, but up to 75 to account for participants who are lost to follow up. Between and within group differences will be evaluated using Fisher's exact test for categorical variables and t‐tests for continuous variables, as the investigators expect the data will be normally distributed. Wilcoxon rank‐sum test will be used for continuous variables that are not normally distributed. If there are any baseline differences between groups, a multivariate analysis will determine the contribution of these differences to observed differences (if any) between groups Data Management/Confidentiality: Participants will be given a de‐identified study subject number. Data collection sheets and questionnaires will contain the subject number. No other patient identifiers will be collected on study forms. PHI including patient name, date of birth, phone number, email address and medical record number will be collected to track appointments and ensure patient follow‐up. The data collection, HIPAA and consent forms will be maintained via REDCap. PHI will not be entered into the study database. The link between PHI and study IDs will be kept on a password protected computer on a secure UNM OBGYN department server. The study database does not include sensitive information or information requiring additional protection. Electronic data entry will be performed on REDCAP, using the de‐identified subject study number. The electronic data and subject link will be encrypted, password protected, and stored on the secure UNM OBGYN department server. This server's electronic security is monitored / maintained by the Health Sciences Library and Informatics Center (HSLIC). A REDCAP database will be created to collect, store and manage the data. REDCAP databases are reposed securely and all data entered is de‐identified. The REDCAP database is only accessible using an individual unique login and password and access is only provided to co‐investigators. Access is restricted to co‐investigators and research staff and will be protected using the unique REDCAP login and password provided to each co‐investigator. Access to the REDCAP will be restricted to research personnel and Investigators and will be locked or password‐protected using the unique REDCAP login and password provided to each co‐investigator. The data will be stored for 6 years after completion of analysis and study closure and then will be destroyed. A Certificate of Confidentiality will not be used to protect data from forced release. No identifying or study related data will be transported to outside locations. There will be no audio or video recordings or photographs taken.

Nct (2023). "The Soft Tissue Mobilization Techniques on PMS." ClinicalTrails.gov.
	The aim of this study is investigate the effects of progressive relaxation and myofascial release technique on blood flow velocity, pain, premenstrual symptoms and quality of life in premenstrual syndrome patients. The study planned as a single‐blind randomized controlled trial. The volunteers who were invited to the study and signed the voluntary consent form will be randomized via random allocation software to divided into 3 groups. These groups are; progressive muscle relaxation group, myofascial relaxation technique and control group. Evaluations will be made by another physical therapist who is blinded to the groups. Participants will be evaluated within the first 3 days of their menstrual cycle. Baseline assessment will be done in the first 3 days of the first cycle, after first treatment acute assessment will be done. Post‐treatment evaluation will be done in the first 3 days of the 3rd cycle after treatment for two cycles. Follow‐up evaluation will be done in the first 3 days of the fifth cycle, two cycles after the post‐treatment evaluation.

Nct (2023). "Soft Tissue Release With and Without Vaginal Dilators on Pain and Sexual Function in Genitio Pelvic Pain." ClinicalTrails.gov.
	Painful sexual intercourse is a common female health problem. It is a complex disorder that often goes neglected. It can be further categorized into superficial or deep, and primary or secondary. Superficial is limited to the vulva or vaginal entrance, while deep means the extension of pain into the deeper parts of the vagina or lower pelvis. Deep dyspareunia is frequently associated with deep penetration. Primary pain initiates at the start of sexual intercourse, while in secondary, pain begins after some time of pain free sexual activity This study will be a randomized clinical trial which will incorporate two different interventions soft tissue release and vaginal dilators use would be administered to the women with genito pelvic pain. Subjects meeting the predetermined inclusion criteria will be divided into two groups using lottery method. Assessment will be done using GPPPD, Vancouver Visual Analogue Scale, female sexual function index and pelvic floor impact questionnaire . Subjects in one group will be treated with soft tissue release and vaginal dilators. And the other will be treated with soft tissue release only. Each subject will receive a total 09 treatment sessions, with 03 treatment sessions per week. Measurements will be recorded at baseline, 5th and 9th treatment session. Recorded values will be analyzed for any change using SPSS21.

Nct (2023). "Strength Training for Osteoporosis Prevention During Early Menopause." ClinicalTrails.gov.
	The STOP‐EM trial will examine a 9‐month supervised, progressive, resistance training program in peri‐ and early menopausal females. Primary outcomes include recruitment rates, protocol adherence, and attrition. A waitlist control group will allow us to examine the effect of the exercise program on bone density, structure, and strength, muscle strength, and menopausal symptoms. Participants will be randomized to the exercise or control group. The exercise group will attend twice weekly, in‐person, supervised, progressive resistance training and build up to 80‐90% of estimated 1 repetition maximum (1RM). The study will take place at the University of Calgary. Findings will be used to decide whether to continue to the definitive trial.

Nct (2023). "Study of ART0380 in Patients With Biologically Selected Solid Tumors." ClinicalTrails.gov.
	ART0380 is being developed as an oral anti‐cancer agent for the treatment of patients with cancers that have defects in deoxyribonucleic acid (DNA) repair. The study will recruit selected patients with advanced or metastatic solid tumors, specifically: ‐ Patients with persistent or recurrent endometrial cancer (EC) ‐ Patients with advanced or metastatic solid tumors of any histology Above patients will be randomized in a 1:1 ratio to one of two dose regimens of ART0380. Safety will be evaluated on a quarterly basis, at a minimum. Patients may continue to receive ART0380 as long as they are continuing to derive benefit from treatment or until disease progression, withdrawal of consent, or until they experience unacceptable drug‐related toxicity.

Nct (2023). "A Study of Jincaopian Tablets on Chronic Pelvic Pain After Pelvic Inflammatory Disease." ClinicalTrails.gov.
	Chronic pelvic pain is the major sequela of pelvic inflammatory disease and it's a common, burdensome, and costly condition that disproportionately affects women. This multicenter, randomized, double‐blind, dose‐parallel, placebo‐controlled phase III clinical trial is designed to evaluate the efficacy and safety of Jincaopian Tablets in the treatment of subjects with chronic pelvic pain after pelvic inflammatory disease. In this trial, 414 subjects were enrolled and randomized to either "Jincaopian Tablets" group, or the "placebo" group in a 2:1 ratio. The treatment period is 12 weeks and the follow‐up period is 4 weeks.

Nct (2023). "A Study of Sovilnesib in Subjects With Ovarian Cancer." ClinicalTrails.gov.
	This is a randomized, phase 1b dose optimization study of sovilnesib in subjects with platinum‐resistant HGSOC. The focus of the proposed clinical study is to establish the RP2D of sovilnesib in HGSOC. An adaptive multi‐cohort design will be used to assess the safety, tolerability, PK, and efficacy of multiple dose levels in parallel to establish the RP2D of sovilnesib. The study will be conducted in 2 parts. Part 1: 10 subjects will be randomized to each of the open dose levels to generate preliminary PK, pharmacodynamic (PD), safety, tolerability and efficacy data. Early stopping rules for safety based on a Bayesian Toxicity Monitoring Design will be applied. Part 2: Based on review of the data from Part 1, 20‐30 additional subjects will be randomized to 2 or more dose levels examined in Part 1. At the end of Part 2, PK, PD, safety, tolerability and efficacy data will be used to determine the RP2D. Early stopping rules for safety based on a Bayesian Toxicity Monitoring Design and for futility based on a Bayesian Efficacy Monitoring via Predictive Probability Design will be applied. Sovilnesib will be given orally in 28‐day cycles at selected dose levels of interest. Dosing will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other stopping criteria are met.

Nct (2023). "Study of V117957 in Overactive Bladder Syndrome." ClinicalTrails.gov.
	The purpose of this study is to evaluate the safety, tolerability and efficacy of V117957 in subjects with overactive bladder syndrome, compared to placebo.

Nct (2023). "Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)." ClinicalTrails.gov.
	Women with locally advanced cervical cancer will be randomized in a 1:1 ratio to receive treatment with Volrustomig or Placebo.

Nct (2023). "A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated With Menopause." ClinicalTrails.gov.
	Researchers are looking for a better way to treat women who have sleep disturbances associated with menopause. Menopause is part of a natural aging process and happens when women's menstrual cycles, also called periods, stop. Sleep disturbances, for example, frequent waking up at night, are a common and bothersome symptom associated with menopause that affects women's quality of life. The study treatment Elinzanetant (also called BAY 3427080) is under development to treat symptoms like hot flashes which are caused by hormonal changes associated with menopause. It may block the activity of a protein that has been found to contribute to sleep disturbances. The main purpose of this study is to learn how does elinzanetant affect sleep disturbances associated with menopause as measured on a sleep test called polysomnography (PSG) as compared with placebo. For this, the researchers will analyze ‐ change in the total number of minutes a participant wakes up at night after going to sleep after 4 weeks of treatment compared to before treatment ‐ change in the total number of minutes a participant wakes up at night after going to sleep after 12 weeks of treatment compared to before treatment ‐ change in the participant's total time asleep while in bed after 4 and 12 weeks of treatment compared to before treatment. The study participants will be randomly (by chance) assigned to one of two treatment groups. Dependent on the group, they will take elinzanetant or placebo for 12 weeks. Each participant will be in the study for approximately 22 weeks (plus potential washout period), including a screening phase of up to 6 weeks, 12 weeks of treatment, and a follow up phase of 4 weeks after the end of treatment. 5 visits to the study site are planned. During the study, the doctors and their study team will: ‐ take blood and urine samples ‐ do physical examinations ‐ check vital signs ‐ do sleep tests ‐ use an electronic hand‐held device to record sleep quality and hot flashes at home An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments.

Nct (2023). "Survivorship Care for Women Living With Ovarian Cancer: (POSTCARE-O)." ClinicalTrails.gov.
	Study Design We will conduct a 2‐arm randomized controlled trial to evaluate the impact of a telehealth delivered survivorship transition care process. Ovarian cancer survivors (120) will be randomly allocated to receive survivorship care either using the POSTCare Process or standard of care. Study design and reporting will be in accordance with the Consolidated Standards of Reporting Trials (CONSORT) checklist. We will use quantitative and qualitative methodologies in a concurrent triangulation mixed methods design utilizing qualitative data to augment our interpretation of quantitative data. Outcomes will be collected at baseline, 12 weeks and 24 weeks, with the primary outcome being quality of life assessment at 12 weeks. Sample Size We will enroll 120 women completing primary treatment for Stage 2‐4 ovarian cancer from 3 urban gynecologic oncology clinics located in the Southern United States. Participants will have received some combination of surgery, chemotherapy, radiation therapy, and biologics. Continued maintenance therapy is not an exclusion factor. Aim 1 proposes to implement a randomized controlled trial (RCT) devised to compare QOL measures among ovarian cancer patient randomized to receive usual care versus the POSTCare survivorship care transition program. The Functional Assessment of Cancer Therapy‐Ovarian (FACT‐O) QOL survey will be collected at baseline as well as 12 and 24 weeks after the initial course of adjuvant chemotherapy. The primary endpoint will be the 12‐week survey. We expect to observe a mean 12‐week FACT‐O score of 116 with standard deviation of 20 for women receiving usual care. The sample size of N=120 patients provides at least 80% power to detect a 7% increase in the mean FACT‐O score for women randomized to the POSTCare survivorship care intervention. This is sufficient to ascertain a minimally important difference of 8 points. Recruitment and Setting We will recruit participants from Gynecologic Oncology practices at 3 clinic settings in Texas: One safety net practice located in Dallas, one safety net practice located in Houston, and one faculty group practice located in Houston. Cumulatively the sites serve approximately 120 eligible patients per year and ensure a diverse population can be recruited during the 24‐month recruitment period. 120 women will be recruited. Sixty participants will be randomly assigned to the intervention group and receive care using the POSTCare Process and 60 will be randomly assigned to the control group. It is anticipated that our study sample will reflect the ethnic and racial diversity of our clinical settings.

Nct (2023). "A Telehealth-delivered Physical Therapy Program for Postmenopausal Women With Urinary Incontinence." ClinicalTrails.gov.
	This is a non‐inferiority randomized controlled trial with a nested cross‐sectional study and a nested qualitative interview study. Sixty community‐dwelling postmenopausal women with urinary incontinence, aged >40 years, will be recruited and randomly allocated to two groups, telehealth group or face‐to‐face group. All groups will receive a 12‐week pelvic floor muscle training. The face‐to‐face group will be supervised by a female physical therapist who will provide pelvic floor muscle training twice a week. The training will be adjusted according to the performance of the participant. The telehealth group will receive eight sessions of individualized pelvic floor muscle training provided by a physical therapist via telehealth in addition to a weekly telephone coaching. The baseline, post‐intervention, and 3‐month follow‐up assessments will include feasibility outcomes, measurements of anthropometry, body composition (body composition monitor), hand grip strength (dynamometer), functional exercise capacity (six minute walk test), and pelvic floor muscle function (vaginal manometry, transperineal ultrasound and digital palpation) and two questionnaires about symptom severity of urinary incontinence and physical activity levels. This study will provide evidence of effectiveness of different delivery modes of physical therapy program for postmenopausal women with urinary incontinence and health‐care professionals working with this population in clinical practice.

Nct (2023). "Telemedicine Use in Preoperative Counseling for Endometrial Cancer Survivors." ClinicalTrails.gov.
	Newly diagnosed endometrial cancer survivors, who are presenting for their initial consultation with a plan for minimally invasive surgery, will be randomized 1:1 to standard counseling or standard counseling plus asynchronous telemedicine video. The asynchronous video will be available outside of the office and can be viewed multiple times. The primary endpoint is patient anxiety, measured via the State‐Trait Anxiety Inventory (STAI) questionnaire, assessed before surgery. The secondary outcomes of anxiety following surgery as well as patient satisfaction with counseling type (measured via the Patient Satisfaction Questionnaire (PSQ‐18)) before and after surgery will be compared between groups. Both groups will complete questionnaires following their initial consultation (but before surgery) and at their post‐operative visit. For the telemedicine group, the duration and frequency of video views will be collected. Participants completing both surveys will receive a survivorship gift bag.

Nct (2023). "Tele-rehabilitation for Female Athletes With Pelvic Floor Dysfunctions." ClinicalTrails.gov.
	Female athletes from EG1 and EG2 will complete the strengthening program for PF three times per week, during six weeks. Each session will last about 20 minutes and exercises will be modified every two weeks to meet the principle of training progression and avoid athletes become bored.

Nct (2023). "Tele-rehabilitation for Women With Urinary Incontinence: a Randomized Controlled Trial." ClinicalTrails.gov.
	The present study is designed to be conducted as a prospective randomized controlled clinical trial (RCT) with three arms. 1. The Telerehabilitation Group will use the mobile app in collaboration with the pelvic floor sensor with the remote supervision of the physiotherapist which will take place in patient's home. 2. Traditional/classical treatment Group will follow PFM exercises program with the physiotherapist, which will take place in a health care environment. 3. Control Group will execute the PFM exercises via a home leaflet, without any supervision. Αll patients will be assessed in three sessions, at baseline (0 wk), half‐way at 6 wks and at the end of the treatment (after 12 wks. Primary outcome measures will evaluate the severity of the incontinence and the quantity of the urinary loss through the patient‐centered International Consultation on Incontinence Questionnaire Short Form (ICIQ‐UI‐SF) and the clinician‐centered '1‐hour Pad test', respectively. Secondary outcomes will include vaginal evaluation through digital palpation using the PERFECT assessment scheme and through an electromyography probe, in order to assess the power and the endurance of the PFMs. The patients will complete patient‐centered outcome measures, such as specific pelvicl floor exercise adherence questionnaire and exercise diary during their treatment, in order to be evaluated on how well they followed the program. Patients will be recruited voluntarily through the University Urology clinic, physician referrals, advertisements in hospitals, posting on the internet, social networks (facebook), etc. Once eligible patients have been selected for treatment, they will fill out an informed consent form. This study adheres to Ethical considerations and the Helsinki Declaration and is approved by the Research Ethics Committee (R.E.C.) of the University of Patras. All patient data are stored anonymously/coded in a secure cloud platform accessed only by the research team members. Imputation methods will be applied to address situations where variables are missing, uninterpretable, or inconsistent. Any adverse events will be addressed and documented, while medical consultation will be accessible if needed. To be ensured the complete allocation concealment of the groups, a randomization process will be used, by a 'blind' researcher who will have no knowledge of the assessment and treatment procedures. Due to the nature of the treatment, the intervention is not blinded between participants and clinicians. However, the analysis of the data will be 'blind' (blind‐assessor) It will be performed an analysis based on the data resulting from the initial grouping of patients by treatment protocol (intention‐to‐treat analysis). The data will be collected in excel tables and through SPSS version 24.0 for Windows and a statistical analysis will be performed. Comparison within the groups before and after the intervention will be performed by ANOVA using repeated measurements. Comparison between groups after the intervention will be performed by the Student t‐test (independent measurements); while the chi‐square test will be used for categorical variables (eg yes, no, etc.). In addition, we will calculate the effect size with 95% confidence intervals for each outcome measure with continuous variables. Effect sizes will be considered large if ≥0.8, moderate if ≥0.5 and small if ≥0.2. Results will be considered statistically significant when p<.05. Finally, the results will be presented in means (M) values and their standard deviations (SD).

Nct (2023). "Telerehabilitation in Chronic Pelvic Pain." ClinicalTrails.gov.
	Telerehabilitation is described as the remote conveyance of healthcare services and clinical information using information and telecommunication technologies involving the internet, wireless satellite, and telephone media to provide a series of rehabilitation services by eliminating the barriers of distance, time, and travel to receive care. There is an abundance of commercially available applications (such as Zoom) offered for health care monitoring and management. Most of the studies have employed telerehabilitation methods with patients who have pain, mainly for assessment or exercise programs. There is not any study on the telerehabilitation application of physical therapy in patients with chronic pelvic pain during the coronavirus pandemic. Our conceptual framework is based on two arguments. First, physiotherapists need physical access to their patients only for a limited number of interventions. Most of the methods used by physiotherapists to treat their patients can be conducted at a distance without having direct access to the patient. Previous studies have shown that telerehabilitation can be used in many cases and provide results on par with face‐to‐face treatment. In fact, self‐administered treatment was found to be effective even in the case of postal treatment where the participants received instruction through postal systems. Second, the pelvic floor area is relatively well‐suited for self‐treatment. Most, if not all, of the exercises and procedures, can be safely conducted by the patients themselves. The patients can even use pelvic wands and dilators for harder‐to‐reach inner release points. Therefore, training the patient and supervising and guiding self‐administered procedures should be sufficiently effective to reduce pelvic pain and reach patient satisfaction in most cases. The aim of the study will show the efficacy of Telerehabilitation‐Based Physical Therapy (TBPT) on pain intensity and treatment satisfaction in patients with chronic pelvic pain.

Nct (2023). "Testing an Evidence-Based Self-Help Program for Infertility-Related Distress in Women." ClinicalTrails.gov.
	Infertility is associated with severe psychological consequences; psychiatric disorders are common, particularly in women, yet current psychological interventions are not specialized to this population and are largely ineffective. The 7‐week Coping with Infertility (CWI) program is a self‐help program based on cognitive behaviour therapy that aims to improve mental health in women and individuals assigned female at birth who are experiencing infertility. This study aims to test the efficacy of the CWI program. In the proposed study, a single‐blind randomized controlled trial, participants will be randomly assigned to either the specialized CWI program or a waitlist/treatment as usual control condition using stratified block randomization. Infertility‐related distress, quality of life, depression, anxiety, and relationship quality will be assessed at baseline, midway through the program, post‐treatment, and biweekly for 16 weeks after treatment. It is expected that participants assigned to the CWI program will show significantly reduced infertility‐related distress, depression, and anxiety, and improved quality of life and relationship quality relative to baseline and the waitlist control condition. Moderation analyses will examine potential treatment moderators including sexual orientation and gender identity, as well as cultural background, disability status, and whether participants are pursuing fertility treatments. Participants who complete the CWI program will also provide qualitative feedback on how the program can be improved. The results of this trial could establish the CWI program as an effective short‐term therapy option for women experiencing infertility, addressing a significant gap in infertility treatment.

Nct (2023). "Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)." ClinicalTrails.gov.
	PRIMARY OBJECTIVE: I. To investigate the efficacy of neratinib plus palbociclib (PD‐0332991) compared to neratinib maleate (neratinib) alone in patients with HER2+ gynecologic cancers and HER2+ solid tumors by evaluating progression‐free survival (PFS). SECONDARY OBJECTIVES: I. To investigate outcome in terms of objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. II. To investigate clinical benefit rate (ORR + stable disease at 16 weeks). III. To evaluate overall (OS) survival. IV. To evaluate the ORR of patients who crossed over from neratinib monotherapy to neratinib‐palbociclib combination. V. To investigate adverse events especially grade 3 and 4 toxicities by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. VI. Collect tissue and provide it to the ComboMATCH Registration Protocol to assess concordance between the diagnostic tumor mutation profile generated by the Designated Laboratories, the pre‐treatment biopsy mutation profile, and the pre‐treatment circulating tumor‐derived deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol. EXPLORATORY TRANSLATIONAL OBJECTIVES: I. To investigate the role of ctDNA‐HER2 status at baseline and during follow up to assess if it predicts response to therapy and disease progression and if it does correlate with tumor tissue based HER2 status. II. To investigate if activation of the pathways of interest (PI3K/mTOR and RB1, CCND1‐CDK4/6 CDK and RAS/RAF/MAPK) in tumor tissue as well as blood/ctDNA correlate with response or resistance to therapy. III. To correlate extent of HER2 amplification with response to treatment and with HER2 expression by immunohistochemistry or fluorescence in situ hybridization (FISH). IV. To correlate the extent of HER2 amplification with HER2 expression by RNA and protein immunohistochemistry (IHC) analyses and FISH. V. To correlate expression of Rb1, CCND1, CCNE1, CDK4/6 protein expression with response to treatment. VI. Assess alteration in RB1‐CDK pathway in neratinib resistant patients at time of progression on monotherapy compared to combination neratinib‐palbociclib. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive neratinib maleate orally (PO) once daily (QD) on days 1‐14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1‐28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo echocardiogram (ECHO) or multi‐gated acquisition scan (MUGA) during screening and on study, and computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study. ARM II: Patients receive neratinib maleate PO QD on days 1‐14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1‐28 and palbociclib PO QD on days 1‐21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study. After completion of study treatment, patients are followed up every 3 months for 2 years.

Nct (2023). "Therapeutic Efficacy in Women With Stress Urinary Incontinence." ClinicalTrails.gov.
	Background/Purpose: Pharmacologic treatments for female stress urinary incontinence (SUI) include duloxetine and imipramine. Duloxetine and Imipramine has been reported to have clinical significant therapeutic efficacy on female SUI and overactive bladder syndrome. However, there was no randomized controlled study to compare duloxetine and imipramine for the treatment of female SUI. Patients and Methods: We will perform a prospective randomized controlled study to recruit 90 female SUI patients at the Obstetrics & Gynecology outpatient clinic of Far Eastern Memorial Hospital. All SUI female patients will be asked to complete ICIQ‐UI, USS, OABSS, and bladder diary before and after 4 weeks' duloxetine versus imipramine treatment.

Nct (2023). "Thromboxane Function in Women With Endometriosis." ClinicalTrails.gov.
	Cardiovascular disease (CVD) is the leading cause of death worldwide. Endometriosis is an independent risk factor for CVD that affects an estimated one in ten women in the world. Endometriosis is a gynecologic condition characterized by invasive extrauterine endometriotic lesions, chronic pain, and systemic inflammation. The expression of thromboxane A2 (TxA2), a product of the inflammatory cyclooxygenase pathway, is upregulated in endometriotic lesions. In the vasculature, TxA2 blocks vasodilation, and induces vasoconstriction. TxA2 diffuses across the innermost layer of cells in the blood vessels, the endothelium, to act directly on its receptors in the vascular smooth muscle. It also inhibits endothelial nitric oxide synthase, thereby decreasing nitric oxide (NO)‐mediated vasodilation ‐‐endothelial dysfunction which is regarded as a critical early event in the development of atherosclerosis and overt cardiovascular disease. Women with endometriosis demonstrate marked endothelial dysfunction compared with healthy controls, but the potential role of TxA2 and its receptors (TP) in this dysfunction have not been investigated. Furthermore, TP play a key role in sensitizing the sensory afferent nerve fibers in pre‐clinical models of cardiovascular disease, leading to an exaggerated blood pressure responses to sympathoexcitatory maneuvers including the exercise pressor reflex. The exercise pressor reflex is the reflex increase in blood pressure in response to the mechanical and metabolic stimuli of exercise. The exaggeration of this reflex response is a strong predictor of major adverse cardiovascular events in cardiovascular disease patients. However, the reflex response to sympathoexcitatory maneuvers has not been characterized in women with endometriosis. Furthermore, TxA2 is a key component in the clotting cascade. An increased production of TxA2 in the platelet cells of women with endometriosis indicates altered platelet function. However, platelet activity in women with endometriosis has not been characterized.

Nct (2023). "To Compare the Efficacy and Safety of Oral SHR 7280 Tablets With Ganirelix Acetate Injection in Infertile Female Subjects." ClinicalTrails.gov.
	This study is a multi‐center, randomized, double‐blind, positive drug‐controlled, non‐inferiority Phase III clinical trial. The study will enroll approximately 316 infertile female subjects undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.

Nct (2023). "To Explore the Benefits of the MonaLisa Touch® System in Gynaecological Cancer Patients Treated by (Chemo)-RT." ClinicalTrails.gov.
	Patients will be randomly (1:1) assigned to the dilators (standard of care) or MonaLisa Touch® system (2 arms). Patients will be stratified for endometrial or cervix cancer, radiotherapy dose and techniques, menopausal status, tumor stage, chemotherapy or not, surgery or not. Patients will begin the Mona Lisa at 3 months, once per month during 6 months while the follow‐up assessment will continue until 12M after end of RT treatment. Patients randomized in dilator arm will also begin 3 months post end of RT and will use them twice every 2 weeks for 12M (as standard of care). Questionnaires (FSFI‐ Female Sexual Function Index [10], SHQ‐22) and VHI (Vaginal Health Index [11]) will be performed before treatment, at 3, 6, 9, 12 and 15M. Partners will also be asked to fill the sexual quality of life questionnaire EORTC SHQ‐22 before and after treatment.

Nct (2023). "To Prevent Type I-II Myoma After TCRM Recurrence by Gonadotropin-releasing Hormone (GnRH )Analogues or Mifepristone." ClinicalTrails.gov.
	Transcervical resection of myoma(TCRM) has a good therapeutic effect while the probability of complete resection of type I and II fibroids is only 55% per procedure on average and a significant number of patients have fibroid remained.At present, there is no standardized treatment option for reducing the remaining submucous fibroids volume and preventing its recurrence after TCRM.The present prospective,multicentre,randomised controlled clinical trial will enrol women after TCRM and treat them with mifepristone(10mg)or GnRHa(3.60mg)for 3 to 6 months,investigating the effective and cost‐effective treatment options after fibroids with TCRM，thus to provide evidence and effectual regiments for reducing remaining fibroids volume and preventing its recurrence.

Nct (2023). "To Study the Effect of SC-FOS Prebiotics in Women With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	The protocol will be discussed with the patients and/or relatives of the patients, who will understand the consequences and advantages of the study and will thus sign the consent. Once informed consent has been obtained, the group to which each patient belongs will be randomly assigned. Patients will be selected according to the inclusion and exclusion criteria of the population diagnosed with PCOS with useful enteral route for random assignment into two groups, one will be administered short‐chain Fructooligosaccharides at a dose of 12 g every 24 hours, another group will be given saline as a placebo to the enteral diet every 24 hours for 10 days. Patients should take the solution on an empty stomach. Once the type of intervention has been determined, the patient will be given the suspensions corresponding to group 1 or placebo, with vials in which the content cannot be visualized, numbered according to the sheet obtained by the corresponding randomization. The initial evaluation will be completed with all the clinical characteristics to be evaluated. The patient will be told that every 24 hours he must take 1 suspension on an empty stomach, which will be prepared at a rate of 12 grams of SC‐FOS in 15 cc of saline solution for the prebiotic preparation vs 15 cc of saline solution for the placebo group. The solution will be administered enterally for 10 consecutive days at a single dose per day, and a reassessment will be made on the seventh day of the clinical characteristics of the patients, to compare and evaluate the results.

Nct (2023). "Toripalimab Plus Actinomycin-D as Fist-Line Treatment for GTN With FIGO Score 5-6." ClinicalTrails.gov.
	The goal of this clinical trial is to evaluate the efficacy and safety of actinomycin‐D with or without toripalimab as fist‐line treatment in patients with gestational trophoblastic neoplasia with FIGO score 5‐6. Eligible Participants will be randomized into two groups. Those in experimental group will receive toripalimab (200mg q2w intravenous) plus actinomycin‐D (1.25mg/m2，2mg max dose, intravenous). While those in control group will receive actinomycin‐D (1.25mg/m2，2mg max dose, intravenous) alone. After normalization of serum β‐human chorionic gonadotropin (β‐hCG) levels, patients will receive 3 cycles of consolidation treatment. Treatment will be continued until completion of treatment, disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is complete remission rate (the proportion of patients achieving complete remission). Secondary endpoints include objective response rate (the proportion of patients achieving complete remission and partial remission), progression‐free survival (time from the treatment initiation to disease progression or death, whichever comes first), disease control rate, duration of response, overall survival (time from the treatment initiation to the date of death or last follow‐up), duration of response (time from the first evidence of response to disease progression or death, whichever comes first) safety, biomarker, ovarian function and quality of life.

Nct (2023). "A Trial Evaluating the Clinical Efficacy and Safety of Hibero SR (Mirabegron) 50 mg and Ditropan (Oxybutynin Chloride) 10 mg in Children Between 5 and 18 Years With Overactive Bladder (OAB)." ClinicalTrails.gov.
	The trial consists of four periods (Screening/ Washout (2 weeks); Baseline; 4 weeks from baseline; 8 weeks from baseline) excluding the safety monitoring period. It is a randomized, open label, parallel group, and active control comparator trial. The subject will be assigned either to Hibero (Mirabegron) 50 mg or Ditropan (Oxybutynin Chloride) 10 mg at baseline (randomization). The subject will be asked to take the IP or active comparator by mouth without crushing the pill for 8 weeks, and the frequency of oral administration depends on the prescribed method.

Nct (2023). "Trial of Exercise and Lifestyle in Women With Ovarian Cancer." ClinicalTrails.gov.
	An anticipated 200 women with newly diagnosed ovarian cancer scheduled to receive chemotherapy (adjuvant chemotherapy after surgery or neoadjuvant chemotherapy before surgery) will be recruited from Smilow Cancer Hospital Network at Yale Cancer Center (YCC) and Sylvester Comprehensive Cancer Center (SCCC) at University of Miami. Participants will be randomized to an exercise and medical nutrition intervention arm with weekly counseling sessions throughout chemotherapy, or a control arm. Study assessments will be conducted at baseline, post‐chemotherapy/end of intervention and at 1‐year post diagnosis. Women who are prescribed neoadjuvant therapy will have additional assessments prior to surgery. Data required to calculate the primary endpoint (relative dose intensity of chemotherapy) will be abstracted from the medical record directly following each chemotherapy session.

Nct (2023). "Trial of Ovarian Vein and Pelvic Vein Embolization in Women With Chronic Pelvic Pain and Pelvic Varices." ClinicalTrails.gov.
	The study is a randomized research trial of bilateral ovarian vein embolization (OVE) and pelvic vein embolization (PVE) in women with chronic pelvic pain (CPP), dilated and incompetent ovarian veins ≥6mm and pelvic varices (≥1 veins, >5 mm diameter) to assess for change in pain. Pain will be assessed by visual analog scale (VAS) and other relevant, validated quality of life metrics including the Patient‐Reported Outcomes Measurement Information System (PROMIS) Item Bank v.1.0 ‐ Pain Intensity, Patient‐Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 ‐ Global Health, Patient Global Impression of Change (PGIC) and EuroQol five‐dimension (EQ 5D). The target population includes women age greater than or equal to 18 years who are pre‐menopausal and have symptoms, and clinical and imaging findings corresponding to Pelvic Venous Disease (PeVD). Subjects will be randomized in a 1:1 fashion to embolization (treatment group) or venography only (control group). Follow‐up will be assessed weekly and at 1, and 3 months and 6 months post procedure to assess for changes in quality of life in patients who receive ovarian/pelvic vein embolization versus no embolization.

Nct (2023). "A Trial of Sperm Injection (PICSI) on Miscarriage Rates in Assisted Conception." ClinicalTrails.gov.
	1. INTRODUCTION 1.1 Background Physiological intracytoplasmic sperm injection (PICSI) is a technique used to select healthy, mature sperm for use in infertility treatment based on their physiological ability to bind to hyaluronic acid (HA), a natural compound found in the body. The relationship between sperm and HA can be used as a marker of sperm maturity and fertilising potential; this principle can be observed in vitro using a PICSI sperm selection device. The PICSI Dish contains microdots of hyaluronan, which only mature sperm bind to and these are selected by the embryologist prior to use in the intracytoplasmic sperm injection (ICSI) procedure. The recent HABSelect study investigated treatment outcomes following PICSI, and whilst they concluded no effect on livebirth rate, they found a significant association in their secondary analysis between PICSI and reduced miscarriage rate compared to ICSI . The implications of the HABSelect study deserve to be explored further with miscarriage rate assessed as a primary outcome measure. This proof‐of‐concept randomised‐controlled‐trial aims to investigate whether PICSI shows some promise that would merit evaluation in a fully‐powered trial to assess its efficacy as an advanced sperm selection method for the reduction of miscarriage rate. Eligible study participants will be patients undergoing fertility treatment using ICSI, who have provided consent for PICSI. Patients will be randomly allocated to two groups: the control group will receive ICSI according to standard protocol, and the intervention group will have additional sperm selection by HA‐binding in a PICSI dish. 1.2 Rationale Advanced sperm selection techniques have been developed to improve ART outcomes to select the healthiest, mature and structurally sound sperm. It is crucial that the best sperm are selected for ICSI, yet conventional sperm preparation methods, including density gradients, swim‐up, and simple wash, are limited in their capacity to select for spermatozoa with maturity and reduced DNA fragmentation. Recurrent miscarriages following infertility treatment are mainly resulting from unknown causes, but can be linked with increased chromosomal abnormalities from aneuploid embryos . Physiological Intracytoplasmic Sperm Injection (PICSI) is an advanced sperm selection method that selects for mature sperm with low DNA damage prior to injecting the oocytes in the ICSI procedure. PICSI has been shown to result in better embryo development and reduced chromosomal abnormalities. PICSI may be a useful tool for reducing the rate of miscarriage following infertility treatment. In the United Kingdom, there are restrictive policies set out by NHS clinical commissioning groups (CCGs) about access to assisted reproductive techniques, where only a limited number of IVF cycles are funded, so it is exceptionally important to maximise chances of transferring a viable embryo which will lead to a successful live birth. The SMWFC has a KPI target of <20% for miscarriage rate and alas the current figure for miscarriages following ICSI treatment is 24%, which is above this threshold. The purpose of this study is to investigate whether it is worth doing a larger study of efficacy to establish whether PICSI reduces the miscarriage rate and could therefore be introduced into practice. 2. STUDY OBJECTIVES 2.1 Primary Objective To establish whether there is any promise of an effect of Physiological Intracytoplasmic Sperm Injection (PICSI) on miscarriage rate compared with conventional ICSI. 2.2 Secondary Objective To investigate whether there is any promise of effect of Physiological Intracytoplasmic Sperm Injection (PICSI) on the fertilisation rate, embryo quality and development, clinical pregnancy rate, or implantation rate compared with conventional ICSI. 2.3 Primary endpoint/outcome The primary outcome measure is miscarriage rate, meaning the number of pregnancy losses following biochemical pregnancy (detection of urinary hcGH). The primary outcome data collected is quantitative categorical data and anal ed in a statistical Fisher's exact test. 2.4 Secondary endpoint/outcome Secondary outcomes that will be compared for PICSI and ICSI: ‐ Fertilisation rate, defined as the number of 2PNs per oocyte inseminated/injected. ‐ Embryo development and quality assessed on day two and three in terms of morphology of embryos, degree of fragmentation, presence of vacuoles, symmetrical size of blastomeres. ‐ Blastocyst development and quality assessed on day 5 and 6 according to the Gardner and Schoolcraft scoring system. ‐ Implantation rate, defined as the number of fetal heartbeats or gestational sacs observed at 6‐7 weeks gestation divided by the number of embryos transferred. ‐ Biochemical pregnancy rate, indicated by the detection of urinary hcGH. ‐ Clinical pregnancy rate based on the detection of a fetal heartbeat or the presence of fetal sac at 6‐7 weeks gestation. ‐ Live birth rate, as the number of live births at ≥37 weeks gestation per embryo transfer. 3. STUDY DESIGN The study will be carried out as a pilot randomised‐controlled‐trial, whereby patients will be randomly allocated to either the intervention (PICSI) group or control (ICSI) group. The simple randomisation aims to eliminate any bias and allows a true comparison of the groups with the additional step of physiological sperm selection in PICSI being the differing factor. Null hypothesis: There is no association between PICSI and reduced miscarriage rate compared to ICSI at the Shropshire and Mid Wales Fertility Centre. Study design: The study is a prospective randomised‐controlled trial designed to compare PICSI (intervention) and standard ICSI (control). The ICSI group is suitable as a control in this study so the only differing variable is the sperm selection by HA‐binding. Couples will be randomly assigned to receive treatment with standard ICSI or receive additional PICSI. Using HA‐binding as a sperm selection tool, the intervention group will have sperm selected physiologically prior to ICSI using PICSI dishes, following ORIGIO recommended methods . Only spermatozoa with a moving tail but no forward motion will be selected for use in ICSI. The fertilisation rate, embryo development, implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate will be compared between the two procedures. Researcher bias: The research student will be unblinded to the allocation of patients to treatment groups, however, treatments will be performed by independent staff who are trained ICSI practitioners. Sample size: The total sample size will be 140. The population being investigated will be couples undergoing infertility treatment with ICSI at the Shropshire and Mid‐Wales Fertility Centre in Shrewsbury. Recruitment of participants will occur over 6 months and based on this time constraint we expect to attain 140 participants. This sample size is estimated to be appropriate for this small‐scale study and feasible based on the number of ICSI treatments performed at the Shropshire and Mid‐Wales Fertility Centre. 4. STUDY SETTING This is a single centre study, carried out at the Shropshire and Mid‐Wales Fertility Centre, which is licensed and monitored by the Human Fertilisation and Embryology Authority. The patient recruitment and study conduct will take place at the Shropshire and Mid‐Wales Fertility Centre. The patient population of interest are couples undergoing fertility treatment using ICSI at the Shropshire and Mid‐Wales Fertility Centre, which is a tertiary care setting. Eligible participants will be patients coming through for treatment and will be identified by clinical staff at the centre who have access to the 'upcoming treatments' schedule. The PICSI and ICSI procedures will take place in the embryology laboratory by qualified embryologists who are also experienced ICSI practitioners. Data collection will take place at the Shropshire and Mid‐Wales Fertility Centre on password‐protected secure desktop computers within a treatment database file. Processing and data analysis will be carried out using the nonymised data on the secure NHS OneDrive system.

Nct (2023). "Two Different Dietary Interventions for Girls With Polycystic Ovary Syndrome." ClinicalTrails.gov.
	The purpose of this study was to investigate the effect of a high meal frequency, low carbohydrate, high protein, high n‐3 PUFA, healthy fatty acid and antioxidant content, low glycemic load Resmena diet or a control diet based on AHA recommendations on anthropometric measurements, body composition, insulin resistance, lipid metabolism levels, inflammatory markers and reproductive endocrine levels in adolescents with obesity and PCOS..Randomized controlled study design was used in the study. Patients in the study were allocated to the control and study intervention groups. Participants were invited to face‐to‐face interviews at the beginning of the study and monthly for 6 months. Anthropometric measurements, body composition analysis, and a physical activity questionnaire were performed at the beginning and end of the study, and three‐day food consumption records and blood samples for the measurement of biochemical parameters were collected. In addition, the physical activity and food consumption records of the participants were repeated in monthly controls and their anthropometric measurements and body composition were analyzed and compared.

Nct (2023). "Urinary Catheter Self-Discontinuation After Urogynecology Surgery." ClinicalTrails.gov.
	This is a prospective, randomized, two‐parallel arm, non‐inferiority trial to evaluate two methods of catheter discontinuation in women with post‐operative urinary retention (POUR) after surgery for pelvic organ prolapse (POP) or stress urinary incontinence (SUI). This study will evaluate whether self‐discontinuation of transurethral catheter by patients is non‐inferior to standard office discontinuation based on rates of persistent POUR on post‐operative day (POD) 1.

Nct (2023). "Use of a Fermented Dairy Beverage in Cervical Cancer Patients Undergoing Concurrent Chemoradiation Therapy." ClinicalTrails.gov.
	Globally, many cancer survivors have undergone radiotherapy (RT) to pelvic tumors, this confers an increased risk of intestinal damage, affecting the quality of life of patients. The role of intestinal microbiota on the development of gastrointestinal toxicity and radiation enteritis has been described in cervical cancer patients that received pelvic RT. In this project we investigated the effect that a fermented dairy beverage (Yakult) may have in the modulation of inflammation and consequently of gastrointestinal toxicity in locally advanced cervical cancer (LACC) patients treated with concomitant chemo‐radiotherapy (CRT). In Mexico, the incidence of cervical cancer is 23 cases in 100,000 women (2015, Secretaría de Salud). In the Mexican National Cancer Institute (Instituto Nacional de Cancerología; INCan), 80% of patients arrive at locally advanced stages (IB2‐IVA), the standard treatment is based on CRT. Gastrointestinal symptoms experienced by patients that receive pelvic RT define the pelvic radiation disease (PRD). Acute PRD is the result of cell death in the crypt epithelium and an acute inflammatory response in the lamina propria, which results in an insufficient replacement of the villi, rupture and inflammation of the mucosal barrier. Symptoms develop in 60‐80% of patients. These include nausea, diarrhea, tenesmus, abdominal pain, urgency, anorexia, bleeding and fatigue; these are dose‐limiting symptoms and affect the patients' quality of life. A recent study analyzed the microbiota of LACC patients and found that patients that develop PRD during treatment with CRT possess a different microbiota to those patients that do not develop severe gastrointestinal toxicity. Evidence points to the critical role that the microbiota and intestinal inflammation play for the development of PRD in LACC patients. Therefore, an optimal intervention that modulates the microbiota is essential. We aimed to investigate the effect that a dairy beverage fermented with the probiotic Lactobacillus casei Shirota may have on intestinal and systemic inflammation, and consequently gastrointestinal symptoms and quality of life in women with LACC, undergoing CRT. METHODS. This study was a double blind, placebo‐controlled trial for Stage IIB cervical cancer patients that underwent CRT. The intervention group consumed of 3 servings of the fermented dairy beverage (Yakult) a day. The control group consumed 3 servings of the placebo beverage (with the same organoleptic qualities of Yakult). Clinical toxicity was analyzed with the Common Toxicity Criteria Version 2. Quality of Life score was measured with the QLQC 30 EORTC questionnaire. Fecal calprotectin was quantified to determine intestinal inflammation. Pro‐ and anti‐inflammatory cytokines were quantified in blood samples to determine systemic inflammation.

Nct (2023). "Use of Misoprostol in Hysteroscopic Myomectomy." ClinicalTrails.gov.
	Hysteroscopic myomectomy is a minimally invasive surgical procedure designed to remove uterine fibroids that are located within the uterine cavity. Traditionally, hysteroscopic myomectomy for large fibroids has been performed as a two‐step procedure, with fibroid removal divided into separate stages. However, advancements in surgical techniques and equipment have allowed for the development of hysteroscopic myomectomy as a one‐step procedure, in which all fibroids are removed in a single surgical session. As a one‐step procedure, hysteroscopic myomectomy offers several potential benefits. It eliminates the need for multiple surgeries and reduces the overall treatment timeline for patients. The size limit for hysteroscopic myomectomy varies among surgeons and institutions. In general, submucosal fibroids up to 4 centimeters in diameter are considered suitable for hysteroscopic resection. Fluid overload is an important consideration in hysteroscopic myomectomy, especially when it is performed as a one‐step procedure, making it a time‐limited procedure. During hysteroscopic myomectomy, a distension media is used to expand the uterine cavity, providing better visualization and creating a working space for the surgeon. However, there is a risk of fluid overload if excessive fluid is absorbed into the bloodstream, potentially leading to complications such as electrolyte imbalances, fluid imbalance, hyponatremia, or cardiovascular issues. To mitigate this risk, certain precautions are taken during the procedure. When the uterus contracts, the fibroid may undergo several changes. These changes can affect the position, size, and accessibility of the fibroid, potentially influencing the surgical approach and outcome. Fibroid extrusion occurs when the fibroid becomes detached from its attachment site and is pushed out of the uterus by the uterine contractions. A case study published by Murakami et al. discussed the contributing effect of intraoperative injection of prostaglandin F2 alpha in a patient undergoing hysteroscopic myomectomy, resulting in a successful one‐step hysteroresectoscopy of a sessile submucous leiomyoma . Additionally, Indman described the effect of intracervical injection of carboprost prior to hysteroscopic resection of submucous myomas that could not be completely resected in a series of 10 case studies . To the investigators knowledge, the use of misoprostol in hysteroscopic resection has been primarily limited to its role as a cervical dilation primer prior to the procedure. The use of misoprostol in hysteroscopy may reduce the need for mechanical cervical dilatation , however, many centers do not use misoprostol routinely in every hysteroscopy.

Nct (2023). "Usefulness of Corifollitropin α as Alternative to Conventional Daily rFSH Protocols in Oocyte Donors Undergoing Pituitary Suppression With Medroxiprogesterona Acetate (MPA)." ClinicalTrails.gov.
	IVF patients frequently experience physical, emotional or physicological burden; this is particularly relevant in the case of oocyte donors, since young women undergo a procedure that is of no health benefit to them. One of the phases of the treatment that contributes most to this situation is ovarian stimulation; as it involves the administration of daily injections which, in addition to the discomfort of administration, causes anxiety to the patient about its correct administration and possible side effects and to physicians concerns about patient compliance. Advances in pharmacology and knowledge of ovarian pathophysiology have led to the development of new protocols that simplify and reduce drug administration, decrease the potential risk of misapplication and contribute to an improved patient experience. In this context, Corifollitropin α, a long‐acting recombinant FSH (rFSH) molecule, provides with a single subcutaneous injection similar results as daily administration of rFSH during a week. On the other hand, conventional stimulation protocols used in ART resort to using a GnRH analogue (agonist or antagonist) to prevent early luteinization, which is defined as the presence of a progesterone value of > 1.5 ng/ml on the day of induced ovulation. Nevertheless, its use presents some disadvantages, such as it being sometimes complex to achieve desensitization or consistent hypothalamic block, risk of OHS when ovulation is triggered with HCG or its cost. Hence the interest in exploring new options to prevent a premature peak in LH. Nowadays, the oral administration of progestagens (progesterone‐primed ovarian stimulation [PPOS]) during the follicular phase of ovarian stimulation (OS) has emerged as an attractive alternative to conventional protocols for preventing early luteinization. Moreover, PPOS produces a similar or even better, in some subgroups, response to OS (length of treatment, number of MII, cancelation rate, etc.), reproductive outcomes (pregnancy rate, live birth rate, etc) and safety (rate of ovarian hyperstimulation [OHSS] or congenital malformations). Thus, PPOS would seem to be an effective option for personalized protocols, particularly when fresh embryo transfer (FET) is not to be performed, a circumstance that is likely to rise in frequency given the progressive increase in women's age at childbearing; for example, in oocyte donation, or in fertility preservation (FP) and preimplantation genetic testing for aneuploidy (PGT‐A). However, very little data are available regarding cycle outcome following Corifollitropin α and PPOS as pituitary suppressor. The present study, a prospective RCT, was designed to evaluate cycle characteristics (MII oocytes as the primary objective) and endocrinologic profiles of oocyte donors receiving Corifollitropin α and MPA as co‐treatment compared with those receiving a daily dose of rFSH (follitropin β) as a control.

Nct (2023). "VACS Device Clinical Study for Incontinence Treatment." ClinicalTrails.gov.
	The study is an open‐label, prospective, parallel‐group, randomized, controlled medical device clinical trial, conducted in two centers. The two arms of the trial consist of patients randomized to the new device group and to the TOT group. According to this distribution, one group will be subjected to the operation with the new device, and the other group will be subjected to the operation with a commercially available TOT. Primary objective: Evaluation of the effectiveness of using the new device in the surgical treatment of urinary incontinence. Secondary objectives: Evaluation of the effects of the new device use on patients' quality of life, treatment satisfaction, and sexual functions, as well as assessment of safety. The study includes evaluation of the progress employing objective (pad weight, number of incontinence episodes, urodynamic tests) and subjective tests (questionnaires, diaries) during the 12 months follow‐up period.

Nct (2023). "Vaginal Orthosis Use After Vaginal Reconstructive Surgery." ClinicalTrails.gov.
	Background/Rationale: Pelvic Organ Prolapse (POP) is the bulging or herniation of one or more pelvic organs into or out of the vagina. A woman's estimated lifetime risk of POP is 30‐50%, with 2‐4% of women being symptomatic. Approximately 300,000 women undergo surgical procedures in the United States to repair POP every year. Recurrence rates of POP after native tissue repair utilizing Sacrospinous Ligament Fixation (SSLF) or Uterosacral Ligament Suspension (USLS) vary based on the definition of surgical or anatomic failure used, however a large RCT reports rate of reoperation at 5 years of 8‐11.9%. With the use of the sacrospinous or uterosacral ligaments for apical support, the long axis of the vaginal canal is deflected posteriorly in the pelvis leaving the anterior wall of the vagina vulnerable to receive more of the downward forces produced intra‐abdominally during activity and with absolute increases in intra‐abdominal pressure. Given this fact, it is not a coincidence that the area of highest recurrence occurs, despite which definition is used, in the anterior vaginal compartment. Currently, the standard of care for post‐operative management in patients who have undergone native tissue pelvic reconstructive surgery is pelvic rest and reduced activity. The Voices for Pelvic Floor Disorders (Voices PFD) in conjunction with the American Urogynecology Society (AUGS) recommend pelvic rest for a minimum of 6 weeks and for activity to "be up and around, but not too active" for the first two weeks, but to increase ambulation and activity as able with guidance from primary surgeon. By the 6‐week post‐operative visit, most patients are ready to begin to return to normal daily activities, but some may take a longer time‐period of reduced activity. The "wound" healing process following vaginal surgery starts immediately after hemostasis is achieved and the surgery is completed. The first stage is the inflammatory stage, which has rapid onset and reaches maximal reaction within 1‐3 days of surgery. This stage is driven by migration of neutrophils and macrophages responding to factors released from the wound site which are responsible for removal of debris and bacteria in order to prepare the site for the second stage of healing, the proliferative stage. The aim of the proliferative stage is to diminish the surgical site tissue area by contraction and fibroplasia, establishing a viable epithelial barrier to activate keratinocytes. This stage is responsible for the closure of the lesion itself, which includes angiogenesis, fibroplasia, and re‐epithelialization. These processes begin in the microenvironment of the lesion within the first 48 hours and can unfold up to the 14th day after the onset of the lesion. With the re‐epithelization initiated and Type III collagen now deposited, the remodeling stage or wound maturation begins. The ultimate goal of this third and final stage is to restore or achieve the maximal tensile strength of the healing tissue. This is achieved mainly through the degradation of Type III collagen and production of Type 1 collagen. The objective of this project is to investigate whether patients who have undergone native tissue pelvic reconstructive surgery for POP would benefit from a supportive intravaginal orthotic device. Participants will be fitted for the device at 2 weeks after surgery with daily use continuing until 12 weeks after surgery, thus providing stabilization during the subepithelial wound healing process leading to improved tissue durability and viability along the repaired vaginal walls.

Nct (2023). "Vaginal Progesterone Improves Clinical Outcomes of RIF Patients." ClinicalTrails.gov.
	According to the enrollment and exclusion criteria, the patients were enrolled, and the subjects were randomly divided into two groups by computer randomization. Group A was the vaginal progesterone added group (test group). Group B was the regular FET group (control group).

Nct (2023). "Virtual Reality (VR) During Peripheral Nerve Evaluation (PNE) Procedure." ClinicalTrails.gov.
	The purpose of this research is to evaluate whether or not wearing a virtual reality headset affects pain and anxiety in patients undergoing percutaneous nerve evaluation (PNE).

Nct (2023). "Yoga and Pilates Based Respiratory Training Effect for Individuals With Urinary Incontinence." ClinicalTrails.gov.
	In the literature, it has been stated that the pelvic floor alone does not play a singular role in maintaining continence, but rather forms a functional unit with the diaphragm, abdominal, and spinal muscles. Since the inability of any of these structures to perform their function properly negatively affects the function of the others, normalization and optimal functioning of the pelvic floor‐thoracic diaphragm relationship are crucial in individuals with urinary incontinence. This study aims to investigate the effectiveness of yoga and Pilates approaches, considering breath as a fundamental building block, through respiration‐based training programs in women with urinary incontinence. The participants who volunteered to take part in the study will be randomly divided into two groups, namely the Yoga‐based Respiration Group (Group 1) and the Pilates‐based Respiration Group (Group 2), using a computer‐assisted randomization program. After the groups are assigned, the initial three sessions for both groups will be conducted face‐to‐face under the guidance of a physiotherapist to ensure the correct execution of the exercises. The exercise program for both groups will consist of approximately 20‐minute sessions, with two sessions per day, five days a week, for a total of six weeks. On the days when face‐to‐face sessions are held, one session will be conducted in‐person, while the other session will be performed at home. During the 3rd and 5th weeks, the exercises will be progressively intensified for both groups to ensure progression, and patients will be called for face‐to‐face sessions. At the end of the six weeks, patients will undergo face‐to‐face evaluations once again.

Neal-Perry, G., et al. (2024). "Effect of fezolinetant on moderate-to-severe vasomotor symptoms according to time of day: pooled data from two randomized phase 3 studies." Menopause 30(12): 1247-1305.
	Objective: Fezolinetant is a nonhormonal agent in development for the treatment of vasomotor symptoms (VMS; hot flashes and night sweats) due to menopause. The efficacy of fezolinetant vs placebo in reducing the frequency and severity of VMS and improving sleep was demonstrated in two phase 3 studies (SKYLIGHT 1 and 2; NCT04003155 and NCT04003142). These and the 52-week SKYLIGHT 4 safety study (NCT04003389) confirmed the safety profile of fezolinetant. Night-time moderate-tosevere VMS can impact quality of life through a significant impact on sleep. To further explore the effect of fezolinetant on night-time VMS episodes post hoc analyses using pooled data from SKYLIGHT 1 and 2 were undertaken. Design(s): SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies with the same design. Women aged >=40- <65 years with moderate-to-severe VMS (minimum average >=7 hot flashes/day) were randomized to once-daily placebo, fezolinetant 30 mg or fezolinetant 45 mg (1:1:1) for 12 weeks. Post hoc analyses assessed the frequency and severity (range 1-3 with 3 being the worst) of VMS between 06:00 and 23:59 (daytime; 18 h), and between 00:00 and 05:59 (night-time period; 6h). Result(s): The pooled dataset comprised 1022 participants who took >=1 dose of study medication: placebo, n=342; fezolinetant 30 mg, n=339; fezolinetant 45 mg, n=341. Reductions in the frequency and severity of daytime and nighttime VMS were observed with fezolinetant compared with placebo. These improvements were seen each week from weeks 1 to 12 apart from one (night-time frequency at week 1 for fezolinetant 45 mg). At week 12, the least squares mean differences vs placebo were numerically greater with fezolinetant 45 mg than with fezolinetant 30 mg (Table). Data at baseline and week 12 are shown in the Table. Improvement for fezolinetant vs placebo is indicated by a least squares mean difference of <0. Further post hoc analyses assessing the relationship between reduction in night-time VMS frequency and severity and improvement in outcomes such as sleep are in progress. Conclusion(s): This pooled analysis demonstrates that fezolinetant 30 mg and 45 mg reduced both the frequency and severity of moderate-to-severe daytime and night-time VMS compared with placebo. SKYLIGHT 1 and SKYLIGHT 2 found that fezolinetant reduced the frequency and severity of VMS compared with placebo in the overall populations, and this post hoc analysis shows consistency of effect at night as well as during the day.

Neena, M., et al. (2022). "Ultra-low vs Low vs Atmospheric Oxygen Tension for Embryo Culture in Assisted Reproduction: A Systematic Review and Meta-Analysis."
	
Negi, R., et al. (2021). "Efficacy of Ginger in the Treatment of Primary Dysmenorrhea: A Systematic Review and Meta-analysis." Cureus 13(3): e13743.
	It has been evidenced that very few systematic reviews have examined the effectiveness of ginger for pain duration and its severity among women with primary dysmenorrhea. This meta-analysis was therefore performed to methodically incorporate and significantly evaluate randomized controlled ginger studies for the treatment of primary dysmenorrhea. The literature was searched using PubMed, Embase, Ovid, ClinicalKey, Medline, and electronic database. We have analyzed clinical trials by comparing ginger with placebo and non-steroidal anti-inflammatory drugs in women with primary dysmenorrhea. The primary outcomes assessed in our meta-analysis were pain severity and pain duration. Secondary outcomes were change in bleeding, side effects of the drug, and rate of satisfaction. We have screened a total of 638 studies, out of which narrative synthesis was formulated for eight studies. We have performed a meta-analysis of five trials examining ginger with placebo and other two randomized controlled trials comparing ginger with a non-steroidal anti-inflammatory drug (NSAID); it seems to be more helpful for relieving menstrual pain than a placebo (mean difference [MD] = 2.67, 95% CI = 3.51-1.84, P = 0.0001, I2 = 86%), although it was found that ginger and NSAIDs were equally effective in pain severity (risk ratios [RR] = 1.15, 95% CI = 0.53-2.52, P = 0.72, I2 =77%). We have not observed any significant difference between ginger and placebo on pain duration among primary dysmenorrheic women (MD = -2.22, 95% CI = -7.62-3.18, P = 0.42, I2 = 56%). Accessible information proposes that oral ginger can be a compelling treatment for primary dysmenorrhea. This meta-analysis strongly supports the requirement for high methodological quality consistency for upcoming trials.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2021, Negi et al.)

Nehemiah, A., et al. (2023). "Intimacy and survivors of cancer with ostomies: findings from the Ostomy Self-management Training trial." Journal of Sexual Medicine 20(11): 1319-1324.
	Background: Many people with abdominal or pelvic cancers require an ostomy during surgical treatment, which can cause significant issues with physical and emotional intimacy in relationships. Aim(s): To evaluate the effect of a telehealth-based education program on intimacy over time for survivors of cancer with ostomies. Method(s): We performed a secondary analysis of our multicenter randomized controlled trial to determine intimacy outcomes and to compare the effects of the Ostomy Self-management Training (OSMT) program vs usual care. Partnered patients were included who provided answers to the City of Hope Quality of Life-Ostomy survey for at least 2 time points during the study. We evaluated the effect of baseline information, such as gender on intimacy. Outcome(s): The primary outcome was intimacy, estimated by a composite score created from questions within the City of Hope Quality of Life-Ostomy survey. Result(s): Of 216 enrolled volunteers, 131 had a partner: 68 in the OSMT arm and 63 in the usual care arm. Of these, 48 were women and 83 were men. The tumor types represented in this study were colorectal (n = 69), urinary (n = 45), gynecologic (n = 10), and other (n = 7; eg, melanoma, liposarcoma). From the cohort, 87 answered the 5 composite intimacy score questions at 2 time points, including baseline. There was significant improvement over time in composite intimacy scores for participants in the OSMT arm vs the usual care arm. Clinical Implications: Our OSMT intervention had a positive effect on factors that contribute to intimacy for survivors of cancer with ostomies, suggesting that a survivorship curriculum can improve their experiences after ostomy surgery. Strengths and Limitations: OSMT allowed for discussion of intimacy and other sensitive topics, which can be challenging. These discussions demonstrate benefit to participants and can serve as frameworks for cancer treatment providers. The focus of this work on partnered participants provides insight into the interpersonal challenges of a life with an ostomy, but it may overlook the important perspectives of nonpartnered participants and the partners themselves. Furthermore, limited power prevented us from conducting subgroup analyses exploring the effects of factors such as gender and tumor type on intimacy. Conclusion(s): At 6-month follow-up, the novel intimacy composite score indicated improvement for participants completing the OSMT intervention. Future research studies with higher power will validate this intimacy measurement and identify intimacy differences in similar populations based on tumor type.Copyright © 2023 The Author(s). Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved.

Nelles-McGee, T., et al. (2023). "Intravenous ketamine for pain control during first trimester surgically induced abortion: Interim analysis of a randomized controlled trial." Journal of Obstetrics and Gynaecology Canada 45(5): 362-363.
	Objectives: Induced abortion is common, with majority completed surgically in the first trimester. IV Ketamine is a sedative and analgesic without the same cardio-respiratory depression risk as IV opioids. Investigating non-opiate pain control for patients with contraindications to opioid analgesia is imperative in the context of the opioid crisis and increasing access to care. This is an interim analysis of (N=45) participants from a randomized controlled trial (RCT) comparing IV Ketamine, oral Morphine, and IV Fentanyl as pain control in first trimester surgically induced abortion. We hypothesize that Ketamine will provide better pain relief than oral Morphine. Method(s): Participants were >=18 years old with ultrasound-confirmed intrauterine pregnancy of gestational age <12 weeks. The trial is a double-blind, single-centre superiority trial of three parallel groups. Primary outcome was assessed using the Visual Analogue Scale (VAS). Result(s): Two participants were excluded post-randomization for (N = 43) participants treated. Ratings of intra-operative pain indicate Ketamine (N = 14) provides better pain control than Morphine (N = 15) and Fentanyl (N = 14, P <0.001). The Ketamine group was more satisfied with anesthetic methods than the Morphine group (P = 0.017). No serious adverse events were observed in any group. Conclusion(s): Findings support RCT continuation and may improve access to more optimal pain control when continuous cardio-respiratory monitoring is unavailable, without increasing adverse events. IV Ketamine emerged as a compelling non-opiate pain control option for patients with opioid allergies, or who experience opioid use disorders, undergoing first trimester abortion induced by surgical methods.Copyright © 2023

Nelson, B. E., et al. (2023). "BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study." npj Precision Oncology 7(1): 19.
	Combined BRAF + MEK inhibition is FDA approved for BRAF V600E-mutant solid tumors except for colorectal cancer. However, beyond MAPK mediated resistance several other mechanisms of resistance such as activation of CRAF, ARAF, MET, P13K/AKT/mTOR pathway exist among other complex pathways. In the VEM-PLUS study, we performed a pooled analysis of four phase one studies evaluating the safety and efficacy of vemurafenib monotherapy and vemurafenib combined with targeted therapies (sorafenib, crizotinib, or everolimus) or carboplatin plus paclitaxel in advanced solid tumors harboring BRAF V600 mutations. When vemurafenib monotherapy was compared with the combination regimens, no significant differences in OS or PFS durations were noted, except for inferior OS in the vemurafenib and paclitaxel and carboplatin trial (P = 0.011; HR, 2.4; 95% CI, 1.22-4.7) and in crossover patients (P = 0.0025; HR, 2.089; 95% CI, 1.2-3.4). Patients naive to prior BRAF inhibitors had statistically significantly improved OS at 12.6 months compared to 10.4 months in the BRAF therapy refractory group (P = 0.024; HR, 1.69; 95% CI 1.07-2.68). The median PFS was statistically significant between both groups, with 7 months in the BRAF therapy naive group compared to 4.7 months in the BRAF therapy refractory group (P = 0.016; HR, 1.80; 95% CI 1.11-2.91). The confirmed ORR in the vemurafenib monotherapy trial (28%) was higher than that in the combination trials. Our findings suggest that, compared with vemurafenib monotherapy, combinations of vemurafenib with cytotoxic chemotherapy or with RAF- or mTOR-targeting agents do not significantly extend the OS or PFS of patients who have solid tumors with BRAF V600E mutations. Gaining a better understanding of the molecular mechanisms of BRAF inhibitor resistance, balancing toxicity and efficacy with novel trial designs are warranted.Copyright © 2023, The Author(s).

Nemenov, M. I., et al. (2022). "Characterization of Patients With and Without Painful Peripheral Neuropathy After Receiving Neurotoxic Chemotherapy: Traditional Quantitative Sensory Testing vs C-Fiber and Adelta-Fiber Selective Diode Laser Stimulation." Journal of Pain 23(5): 796-809.
	Painful chemotherapy induced peripheral neuropathy (CIPN) is a common complication of chemotherapy with drugs such as taxanes and platinum compounds. Currently, no methods are available for early detection of sensory changes that are associated with painful CIPN, nor are there biomarkers that are specific to painful CIPN. This study aimed to compare Diode Laser fiber type-selective stimulator (DLss), a method to selectively stimulate cutaneous C and Adelta fibers, to traditional quantitative sensory testing (QST) in determining psychophysical differences between patients with painful CIPN and a control group. Sensory testing was performed on the dorsal mid-foot of 20 patients with painful neuropathy after taxane- or platinum-based chemotherapy, and 20 patients who received similar neurotoxic chemotherapy, without painful CIPN. In a multivariable analysis, C-fiber to Adelta fiber detection threshold ratio, measured by DLss, was significantly different between the groups (P <.05). While QST parameters such as warmth detection threshold were different between the groups in univariate analyses, these findings were likely attributable to group differences in patient age and cumulative chemotherapy dose. Perspective(s): In this study, fiber-specific DLss test showed potential in identifying sensory changes that are specific for painful neuropathy, encouraging future testing of this approach as a biomarker for early detection of painful CIPN. Trial registration: The study was approved by the Washington University Institutional Review Board (#201807162) and registered at ClinicalTrials.gov (NCT03687970).Copyright © 2021 United States Association for the Study of Pain, Inc.

Nemeth, Z., et al. (2023). "Self-management of vaginal cube pessaries may be a game changer for pelvic organ prolapse treatment: a long-term follow-up study." International Urogynecology Journal 34(4): 921-927.
	Introduction and hypothesis: Loss of anatomical support for the pelvic organs results in pelvic organ prolapse (POP). We hypothesized that daily self-management of a cube pessary might be a safe, feasible long-term treatment in women with symptomatic POP. Method(s): A cohort of 214 symptomatic POP patients (stage 2+) were enrolled prospectively (January to December 2015). Each patient was size-fitted with a space-filling cube pessary and completed a questionnaire online or by phone >=5 years after her initial fitting. Change in quality of life (QoL) was measured with the Patient Global Impression of Improvement (PGI-I). Result(s): Of 185 women included in our analyses, 174 (94%) were continuing to use their pessary 4 weeks post-insertion. Among those, 143 (82.2%) used the pessary successfully for >=5 years. A large majority of these patients (88.8% [127 out of 143]) described their condition as much or very much improved compared with their pretreatment status (PGI-I). Adverse secondary effects (ASEs) were infrequent [15.4% (22 out of 143)]; when they did occur, they were mild, including smelly vaginal discharge (15 out of 22) and slight vaginal bleeding caused by the fitting procedure (6 out of 22). Conclusion(s): Daily self-management of cube pessaries was found to be a safe and effective treatment for improving POP-related symptoms and QoL in the long term.Copyright © 2022, The Author(s).

Neo, Y., et al. (2022). "Time from Surgery to Chemotherapy for Ovarian Cancer Patients: A Single-Centre Retrospective Audit." Australian and New Zealand Journal of Obstetrics and Gynaecology 62(Supplement 1): 47.
	Introduction: The association between time to chemotherapy (TTC) and survival outcomes in patients with ovarian, tubal and peritoneal (OTP) cancer is unclear, although the National Gynae-Oncology Registry (NGOR) quality indicators recommend chemotherapy within 28 days. Aim(s): We aim to describe the TTC for OTP cancer patients treated with primary debulking surgery (PDS) at the centre, compare findings with current recommendations, and explore how TTC correlates with survival outcomes. Method(s): We reviewed the data of OTP cancer patients from 2010-2020 who were treated with PDS at this centre, and subsequently received adjuvant chemotherapy at any centre (n = 190). Descriptive and baseline statistics were compared between TTC <=28 days and >28 days groups. Survival curves were generated for patients diagnosed from 2010-2016 (n = 129). Result(s): One hundred and four of 190 patients (54.7%) had a TTC <=28 days, and 162 (85.3%) had a TTC <=42 days. Median TTC was 28 days (range 6-134, interquartile range 23-35). Women receiving chemotherapy at a private institution were more likely to have a TTC <=28 days (p = 0.042), but there were no other statistically significant differences. Median survival was 95 months (all patients) and 54 months (stage III & IV only). There was no statistically significant difference in survival between the TTC <=28 days and >28 days cohorts. Discussion(s): The majority of patients at the centre received chemotherapy within the recommended timeframe. Our data do not indicate a survival difference with increased TTC. Further studies with larger cohorts and more complex statistical analyses are needed to outline the optimal TTC.

Neonc, T. and Inc (2023). Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis.
	This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 alone for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH- mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled metastases to the brain. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

Neumann, B., et al. (2024). "The impact of fibroid treatments on quality of life and mental health: a systematic review." Fertility and Sterility 121(3): 400-425.
	Fibroids significantly impact the quality of life (QOL) and mental health of affected women. However, there are limited comparative data on QOL measures after medical, surgical, and radiologic interventions in women with fibroids. This study aimed to assess the current literature evaluating the impact of fibroids on QOL measures using several validated questionnaires for radiologic, medical, or surgical interventions or a combination of interventions before and after treatment. PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library were searched from January 1990 to October 2023 to evaluate the available evidence, and the risk of bias was assessed using Cochrane RoB 2.0 or the Newcastle-Ottawa Scale. The review criteria included randomized controlled trials (RCTs) and observational cohort studies that included premenopausal women with symptomatic uterine fibroids, confirmed by imaging, who underwent an intervention to target fibroid disease. Only reports using validated questionnaires with a numerical baseline (pretreatment) and posttreatment scores were included. The exclusion criteria included perimenopausal or postmenopausal patients, conditions in addition to uterine fibroids that share similar symptoms, or studies that did not focus on QOL assessment. Abstracts were screened, and full texts were reviewed to determine whether studies met the inclusion criteria. A total of 67 studies were included after final review: 18 RCTs and 49 observational studies. All interventions were associated with a significant improvement in uterine fibroid-specific QOL measures, mental health metrics, and a reduction in symptom severity scores after treatment. These data reveal a substantial impact of uterine fibroids on the QOL and mental health of women with fibroids and indicate the metrics that can be used to compare the effectiveness of fibroid treatment options.Copyright © 2024 American Society for Reproductive Medicine

Neumann, K., et al. (2023). "Is the algorithm derived, maximum daily dose of 12mg follitropin delta indeed sufficient, even for women considered at risk for underexposure?" Human Reproduction 38(Supplement 1): i480-i481.
	Study question: Does the follitropin delta (FD) dosing algorithm potentially underexpose high body weight (BW) women, especially those with a low ovarian reserve? Summary answer: Our data indicate no decrease of ovarian response with increasing BW in women with serum AMH >15pmol/L treated with daily FD 12mg. What is known already: The FD dosing algorithm stipulates a 1stcycle dose of daily 12mg FD (equivalent to approximately daily 188 IU rFSH) for patients with serum AMH >15pmol/L (2.1ng/ml), irrespective of BW. In trial and real-word study populations (ESTHER-1, 2017; Blockeel, 2022), respectively, nearly 40-50% of patients are thereby exposed to the same 12mg FD dose. In the phase III trial (ESTHER-1), however, only 5% of patients had a BW<85kg. It has so-far been unclear, if women with high BW, e.g. large volume- of-distribution, are potentially underexposed by the algorithm dose of 12mg daily FD, especially when in the AMH 7-15pmol/L strata. Study design, size, duration: A single, university center, retrospective analysis of all (n=337) stimulation cycles with FD treatment performed from 12-June-2016 to 10-Dec-2021. FD was prescribed according to the summary of product characteristics in all patients. BW was assessed in the center on cycle day two or three. Primary outcome is the cumulus-oocyte-complex (COC) number retrieved. A target response is defined as 8-14 COCs, in line with the ESTHER-1 study. Participants/materials, setting, methods: Women with an indication for IVF or ICSI, treatment naive (e.g., 1st cycle), undergoing controlled ovarian stimulation in a GnRH-antagonist protocol with hCG or GnRH-agonist triggering for fresh or frozen-thawed transfer. There was no restriction on AMH levels, BW, cycle regularity or presence of PCOS. Data are shown as mean standard deviation and/or median and range, as appropriate, or proportion. Main results and the role of chance: Inclusion of 182 first cycles with mean age 33 +/-4.2 years (22-44 years), AMH 25.4 +/-16.7 pmol/L (>0.07- 97.86) and BW 72.6 +/-16.3 kg (47-135). 37 out of 182 (20%) women had a BW<85kg. Median COC number was 7 (0-19) in women with BW>85kg and 7 (2-20) COCs with BW>= 85kg receiving 12mg FD in the AMH >15pmol/L stratum (p<0.05). A separate comparison by BW strata and AMH strata 0-7 and 7-15 pmol/L, respectively, also indicated no decrease of ovarian response with higher BW. Overall, in all maximally dosed 12 mg cycles (75/182, 41%), a target response was achieved in 32.7% of patient cycles in women with BW>85kg and 35.7% in women with BW >= 85kg. In patients with AMH >= 15pmol/L, 21/70 patients (30%) had >8 COCs. While no difference in age, BMI, and mean FD dose was observed for those, they were on average taller (1.71 +/-0.06m vs. 1.66 +/-0.06m; p=0.01), showed a tendency for an increased BW (73kg (48-110kg) vs. 63kg (47- 119kg), p=0.08) and body surface (1.87 +/-0.21 vs. 1.76 +/-0.2m2, p=0.05) vs. patients with target response. In all subgroups, the prevalence of cycle irregularity was not different between target and hypo- or hyperresponding patients. Limitations, reasons for caution: The cohort is uncontrolled and the analysis is of retrospective nature. Women with high BW are relatively rare limiting the sample size and power. High BW may be associated with alterations of follicular recruitment and ovarian physiology. Wider implications of the findings: The maximum FSH dose for low ovarian reserve patients is debated (ESHRE COS guideline 2020). The FD algorithm predicts a maximum response at 12mg FD, e.g. equivalent to only approximately 188 IU FSH/day, in all women with AMH >15pmol/L. Our analysis supports this assumption.

NeuTherapeutics and o. Arizona University (2023). PhytoSERM for Menopausal Hot Flashes and Sustained Brain Health.
	No Results Available Dietary Supplement: PhytoSERM|Drug: Placebo Hot Flash Composite score|Trail Making Test score|NIH Toolbox List Sorting Working Memory Test score|NIH Toolbox Picture Sequence Memory Test|NIH Toolbox Auditory Verbal Learning Test|NIH Toolbox Oral Symbol Digit Test|Pittsburgh Sleep Quality Index (PSQI)|Menopause Rating Scale score|Bone Mineral Density (BMD)|Bone Mineral Content (BMC)|Body Mass Index (BMI)|Total Fat Mass (TFM)|Total Lean Mass (TLM) Female Phase 2 132 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment Phyto-HF-2022-01 November 15, 2024

Nevezhkina, T. A., et al. (2023). "EVALUATION OF THE INFLUENCE OF INOSINE PRANOBEX ON THE MATRIX PROTEIN SYSTEM IN PATIENTS WITH CHRONIC VIRAL CERVICITIS." Medical Immunology (Russia) 25(4): 863-870.
	The reproductive potential of both women and men is declining every year. Many factors contribute to the violation of the reproductive function - chemical, physical, mechanical, psychogenic, however, biological factors have the most pronounced effect on reproduction. Chronic viral cervicitis can be not only the cause of infertility and reproductive losses, but also the development of intraepithelial dysplasia, as well as cervical cancer. PVI, as a monoinfection, is quite rare along with HPV. Other UGIs (urogenital infections) act as common routes of transmission and entry gates. The most common association with PVI is herpesvirus infection. An increase in MMP, both systemically and at the local level, may indicate a violation of cell modeling processes, which contributes to the development of autoimmune inflammation with further destruction of the tissues of the reproductive tract. Activation of MMP promotes the release of HSV from the nerve ganglia and reactivation of the infection. Therapy for HPV and HVI (herpes virus infections) are debatable. There is no single standard of treatment, but there are a number of drugs that have antiviral and immunomodulatory effects. Currently, there are no studies on the dynamics of the effect of HPV and HSV infection on the state of MMPs and TIMPs during Inosine pranobex therapy. Objective(s): to evaluate changes in matrix metalloproteinases 2 and 9 and their tissue inhibitors types 1 and 2 in patients with human papillomavirus and herpes infections after Inosine pranobex therapy. 6 patients with papillomavirus and herpetic infections were examined and treated with drugs containing the active ingredient Inosine pranobex. The levels of MMP-2, MMP-9 and TIMP-1, TIMP-2 in blood serum were determined using specific reagents from R&D Diagnostics Inc. (USA). The dynamics of indicators in the blood serum of patients with PVI showed a decrease in the level of MMP-2, MMP-9, TIMP-1 with a simultaneous increase in TIMP-2 relative to the values before therapy. In patients with PVI and HVI, Inosine pranobex therapy showed a decrease in MMP-2 and MMP-9 levels, no changes in the content of TIMP-1, but an increase in the serum content of TIMP-2. Prior to the use of therapy, an increase in the ratio in the main groups in comparison with the control group was found, however, the largest increase was found in the group with the association of infections. After therapy, positive dynamics was established in the main groups. Thus, the ratio in group I decreased and became equal to the control values. In the II group of patients, the ratio, despite the decrease, remained higher than the control values and higher in comparison with the I group of women.Copyright © Nevezhkina T.A. et al., 2023.

New, F. J., et al. (2021). "Outcomes related to percutaneous nephrostomies (Pcn) in malignancy-associated ureteric obstruction: A systematic review of the literature." Journal of Clinical Medicine 10(11): 2354.
	Background: Malignant ureteric obstruction occurs in a variety of cancers and has been typically associated with a poor prognosis. Percutaneous nephrostomy (PCN) can potentially help increase patient longevity by establishing urinary drainage and treating renal failure. Our aim was to look at the outcomes of PCN in patients with advanced cancer and the impact on the patients' lifespan and quality of life. Material(s) and Method(s): A literature review was carried out for articles from 2000 to 2020 on PCN in patients with advanced malignancies, using MEDLINE, EMBASE, Scopus, CINAHL, Cochrane Library, clinicaltrials.gov, and Google Scholar. All English-language articles reporting on a minimum of 20 patients who underwent PCN for malignancy-associated ureteric obstruction were included. Result(s): A total of 21 articles (1674 patients) met the inclusion criteria with a mean of 60.2 years (range: 21-102 years). PCN was performed for ureteric obstruction secondary to urological malignancies (n = -633, 37.8%), gynaecological malignancies (n = 437, 26.1%), colorectal and GI malignancies (n = 216, 12.9%), and other specified malignancies (n = 205, 12.2%). The reported mean survival times varied from 2 to 8.5 months post PCN insertion, with an average survival time of 5.6 months, which depended on the cancer type, stage, and previous treatment. Conclusion(s): Patients with advanced malignancies who need PCN tend to have a survival rate under 12 months and spend a large proportion of this time in the hospital. Although the advent of newer chemotherapy and immunotherapy options has changed the landscape of managing advanced cancer, decisions on nephrostomy must be balanced with their survival and quality of life, which must be discussed with the patient.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Newhouser Laura, M., et al. (2022). "SSRIs vs. SNRIs for Vasomotor Symptoms of Menopause." American family physician 105(4): 430-431.
	
Newman Diane, K., et al. (2023). "Comprehensive pelvic muscle assessment: Developing and testing a dual e-Learning and simulation-based training program." Neurourology and Urodynamics 42(5): 1036-1054.
	Objective: The Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium launched the RISE FOR HEALTH (RISE) national study of women's bladder health which includes annual surveys and an in-person visit. For the in-person exam, a standardized, replicable approach to conducting a pelvic muscle (PM) assessment was necessary. The process used to develop the training, the products, and group testing results from the education and training are described.; Methods: A comprehensive pelvic muscle assessment (CPMA) program was informed by literature view and expert opinion. Training materials were prepared for use on an electronicLearning (e-Learning) platform. An in-person hands-on simulation and certification session was then designed. It included a performance checklist assessment for use by Clinical Trainers, who in collaboration with a gynecology teaching assistant, provided an audit and feedback process to determine Trainee competency.; Results: Five discrete components for CPMA training were developed as e-Learning modules. These were: (1) overview of all the clinical measures and PM anatomy and examination assessments, (2) visual assessment for pronounced pelvic organ prolapse, (3) palpatory assessment of the pubovisceral muscle to estimate muscle integrity, (4) digital vaginal assessment to estimate strength, duration, symmetry during PM contraction, and (5) pressure palpation of both myofascial structures and PMs to assess for self-report of pain. Seventeen Trainees completed the full CPMA training, all successfully meeting the a priori certification required pass rate of 85% on checklist assessment.; Conclusions: The RISE CPMA training program was successfully conducted to assure standardization of the PM assessment across the PLUS multicenter research sites. This approach can be used by researchers and healthcare professionals who desire a standardized approach to assess competency when performing this CPMA in the clinical or research setting. (© 2023 Wiley Periodicals LLC.)

Newman, D. K., et al. (2023). "Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis from the Double-Blind, Randomized, Controlled EMPOWUR Trial." Urogynecology 29(1): 48-57.
	Importance: The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer beta 3 -adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI). Objective(s): This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women. Study Design: In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and urgency episodes. Safety was assessed through adverse events (AEs). Result(s): Of the patients included in the analysis, 1286 (84.9%) were women (vibegron, n = 463; placebo, n = 459; tolterodine, n = 364). At week 12, women receiving vibegron showed significant reductions (95% confidence intervals of least squares mean differences does not include 0) from baseline versus placebo in mean daily micturitions, UUI episodes, and urgency episodes, with least squares mean differences (95% confidence intervals) of -0.5 (-0.8 to -0.2), -0.7 (-1.0 to -0.4), and -0.8 (-1.3 to -0.4), respectively. Treatment-emergent AE incidence was similar with vibegron (39%) and placebo (35%); the most common AE with incidence higher with vibegron (4.3%) than placebo (2.6%) was headache. Conclusion(s): In this subgroup analysis, women receiving vibegron showed significant reductions in key efficacy end points versus placebo and favorable safety profile, consistent with the overall results from EMPOWUR, suggesting that vibegron is efficacious and safe for the treatment of OAB in this patient population.Copyright © 2022 The Author(s).

Newman, L. J., et al. (2022). "A Systematic Review of Music Interventions to Support Parent-Child Attachment." Journal of music therapy 59(4): 430-459.
	Secure attachment in early childhood is important for wellbeing throughout life. Music interventions show promise for supporting early parent-child relationships; however, their effects on attachment security are unclear as few music intervention evaluations have measured attachment outcomes. This systematic literature review aimed to synthesize published empirical literature examining the effects of music interventions on relationship quality between typically developing children aged birth to 5 years old and their parents. The study aimed to: (1) establish whether music interventions were associated with changes in attachment-related outcomes; (2) identify music intervention characteristics likely to support secure attachment; and (3) elucidate processes through which music techniques may have contributed to attachment-related changes. Included interventions focused on the parent-child dyad, involved a substantial music component delivered by a music therapist or an allied health professional, and assessed and/or described relationship outcome/s. A total of 23 studies describing 15 unique interventions met criteria for inclusion and represented approximately 808-815 parent-child dyads. Mothers were the most common caregivers. All interventions demonstrated some effectiveness, including in attachment-related outcomes such as bonding, emotional co-regulation, and parental sensitivity. All interventions involved singing, suggesting it may be especially suitable for supporting parent-child attachment; other music techniques used included instrument playing and movement to music. Findings suggested that music interventions may facilitate attachment-related changes through intervening in psychological processes, including parental sensitivity, reflective functioning, and emotional co-regulation. Future research should develop music interventions aiming specifically to support attachment quality, and music intervention evaluations should use validated attachment assessments and longitudinal study designs.

Newton, M., et al. (2022). "Survival comparison of chemotherapy vs. chemotherapy plus surgery for women with ovarian cancer with distant metastatic disease (387)." Gynecologic Oncology 166(Supplement 1): S197-S198.
	Objectives: Standard treatment of advanced epithelial ovarian cancer (EOC) is a combination of surgical cytoreduction and chemotherapy. However, the impact of cytoreductive surgery for patients with unresectable metastatic disease, in whom optimal cytoreduction is not feasible, is not well described. Method(s): The National Cancer Database (NCDB) was used to identify patients with Stage IV EOC with distant organ metastasis at the time of diagnosis, treated from 2005 to 2016. Distant organ metastasis was defined as metastasis to the brain, lung, liver, bone, or distant lymph node. To represent unresectable distant metastasis, a restricted population with only metastasis to the brain, lung, or bone was also analyzed. All patients received chemotherapy with or without surgery. Overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards models, and propensity score-weighted analyses. In these analyses, the variables included were surgery, age, year of diagnosis, race, Charlson/Deyo Comorbidity Condition (CDCC) Score, facility type, primary insurance, histology, site of metastasis, urban versus rural residence, education, and median household income. Result(s): We identified 9025 patients with EOC with distant organ metastasis in the NCDB. Among these patients, 2074 received chemotherapy alone, and 6951 received chemotherapy plus surgery (C+S). Those who received chemotherapy alone were older with higher CDCC scores, lived in areas of lower median household incomes, and had lower high school graduation rates. These individuals had a higher proportion of metastatic disease to the liver, bone, or brain. Race was significantly different between groups, with a higher proportion of those receiving chemotherapy alone being Black (12.7% vs 8.2%). Survival was significantly improved for patients who received C+S (HR: 0.46, p<0.0001). Propensity score-weighted analysis similarly showed improved survival for patients undergoing C+S (HR: 0.49, p<0.0001). Individuals who received single-agent chemotherapy had worse overall survival (HR: 1.35, p<0.0001). When accounting for the impact of single-agent chemotherapy on the survival comparison, the benefit of surgery remained significant (HR: 0.47, p<0.0001). In the group defined as unresectable distant metastasis, we identified 1424 patients, of which 396 received chemotherapy alone and 1028 received C+S. A survival benefit was again shown for patients who received C+S, by Cox model (HR: 0.42, p<0.0001) and propensity score-weighted analysis (HR: 0.44, p<0.0001). Conclusion(s): Despite the poor prognosis associated with Stage IV EOC, obtaining local control with surgery in addition to chemotherapy may provide an added oncologic benefit. Because of the retrospective nature of this analysis, the absolute benefit of surgery for patients with Stage IVB EOC cannot be established. However, this study may provide added value to patient-centered counseling on the role of surgical resection in the setting of ovarian cancer with distant metastatic disease.Copyright © 2022 Elsevier Inc.

Nezhat, C., et al. (2020). "Reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer: a systematic review." Fertility and Sterility 113(4): 685-703.
	This review sought to evaluate the current literature on reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer (stage IA1-IB1) including cold-knife conization/simple trachelectomy, vaginal radical trachelectomy, abdominal radical trachelectomy, and laparoscopic radical trachelectomy with or without robotic assistance. A systematic review using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist to evaluate the current literature on fertility-sparing surgery for early stage cervical cancer and its subsequent clinical pregnancy rate, reproductive outcomes, and cancer recurrence was performed. Sixty-five studies were included encompassing 3,044 patients who underwent fertility-sparing surgery, including 1,047 pregnancies with reported reproductive outcomes. The mean clinical pregnancy rate of patients trying to conceive was 55.4%, with the highest clinical pregnancy rate after vaginal radical trachelectomy (67.5%). The mean live-birth rate was 67.9% in our study. Twenty percent of pregnancies after fertility-sparing surgery required assisted reproductive technology. The mean cancer recurrence rate was 3.2%, and the cancer death rate was 0.6% after a median follow-up period of 39.7 months with no statistically significant difference across surgical approaches. Fertility-sparing surgery is a reasonable alternative to traditional radical hysterectomy for early-stage cervical cancer in women desiring fertility preservation. Vaginal radical trachelectomy had the highest clinical pregnancy rate, and minimally invasive approaches to fertility-sparing surgery had equivalent oncologic outcomes compared with an abdominal approach. The results of our study allow for appropriate patient counseling preoperatively and highlight the importance of a multidisciplinary approach to achieve the best outcomes for each patient. (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Nezhat, F., et al. (2022). "A systematic review of the reproductive and oncologic outcomes of fertility-sparing surgery for early-stage cervical cancer." Journal of the Turkish German Gynecological Association 23(4): 287-313.
	In this review, we aim to evaluate the current literature on reproductive and oncologic outcomes after fertility-sparing surgery for early-stage cervical cancer (stage IA1-IB1). This is a systematic review of the existing literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist to report on fertility-sparing surgery and its outcomes in early-stage cervical cancer. Outcomes of interest were subsequent clinical pregnancy rate, reproductive outcomes, and cancer recurrence outcomes. Included in this systematic review were 68 studies encompassing 3,592 patients who underwent fertility-sparing surgery. Of these, reproductive outcomes were reported in 1096 pregnancies. The mean clinical pregnancy rate was 53.2%. Those who underwent vaginal radical trachelectomy had the highest clinical pregnancy rate (67.5%). The mean live birth rate was 67.8% in our study. Twenty-one percent of pregnancies after fertility-sparing surgery required assisted reproductive technology. The mean cancer recurrence rate was 3.2%, and the cancer death rate was 0.6% after a median follow-up period of 40.1 months with no statistically significant difference across surgical approaches. Offering fertility-sparing surgery in early-stage cervical cancer is reasonable. Highest clinical pregnancy rate is associated with vaginal radical trachelectomy. Moreover oncologic outcomes of minimally invasive approaches were comparable with abdominal approaches. We encourage detailed preoperative counseling and multidisciplinary approach to achieve best outcomes.

Ng, A. P., et al. (2022). "Insurance-based disparities and risk of financial toxicity among patients undergoing gynecologic cancer operations." Gynecologic Oncology 166(2): 200-206.
	Objective: To evaluate the risk of financial toxicity (FT) among inpatients undergoing gynecologic cancer resections and the association of insurance status with clinical and financial outcomes. Method(s): Using the 2008-2019 National Inpatient Sample, we identified adult hospitalizations for hysterectomy or oophorectomy with a diagnosis of cancer. Hospitalization costs, length of stay (LOS), mortality, and complications were assessed by insurance status. Risk of FT was defined as health expenditure exceeding 40% of post-subsistence income. Multivariable regressions were used to analyze costs and factors associated with FT risk. Result(s): Of 462,529 patients, 49.4% had government-funded insurance, 44.3% private, and 3.2% were uninsured. Compared to insured, uninsured patients were more commonly Black and Hispanic, admitted emergently, and underwent open operations. Uninsured patients experienced similar mortality but greater rates of complications, LOS, and costs. Overall, ovarian cancer resections had the highest median costs of $17,258 (interquartile range: 12,187-25,491) compared to cervical and uterine. Approximately 52.8% of uninsured and 15.4% of insured patients were at risk of FT. As costs increased across both cohorts over the 12-year study period, the disparity in FT risk by payer status broadened. After risk adjustment, perioperative complications were associated with nearly 2-fold increased risk of FT among uninsured (adjusted odds ratio 1.75, 95% confidence interval 1.46-2.09, p < 0.001). Among the insured, Black and Hispanic race, public insurance, and open operative approach exhibited greater odds of FT. Conclusion(s): Patients undergoing gynecologic cancer operations are at substantial risk of FT, particularly those uninsured. Targeted cost-mitigation strategies are warranted to minimize financial burden.Copyright © 2022 The Authors

Ng Beng, K., et al. (2023). "Maternal and fetal outcomes of pregnant women with bacterial vaginosis." Frontiers in surgery 10: 1084867.
	Background: Bacterial vaginosis (BV) is a common infection in women of reproductive age group because of vaginal dysbiosis. The impact of BV during pregnancy is still not well defined. The objective of this study is to assess the maternal-fetal outcome in women with BV.; Materials and Methods: A prospective cohort study over one-year duration was conducted from December, 2014 until December, 2015, involving 237 women who presented with abnormal vaginal discharge, preterm labour or preterm prelabour rupture of membrane between 22- and 34-weeks period of gestation. Vaginal swabs were sent for culture and sensitivity, BV® Blue testing and PCR for Gardnerella vaginalis (GV).; Results: BV was diagnosed in 24/237 (10.1%) cases. The median gestational age was 31.6 weeks. GV was isolated from 16 out of 24 (66.7%) in the BV positive group. There was a significantly higher preterm birth rate, below 34 weeks (22.7% vs. 6.2%, p = 0.019) in women with BV. There was no statistically significant difference in maternal outcome such as clinical chorioamnionitis or endometritis. However, placental pathology revealed more than half (55.6%) of women with BV had histologic chorioamnionitis. Neonatal morbidity was significantly higher with exposure to BV, with a lower median birth weight, higher rate of neonatal intensive care unit admission (41.7% vs. 19.0%, p = 0.010), increased intubation for respiratory support (29.2% vs. 7.6%, p = 0.004) and respiratory distress syndrome (33.3% vs. 9.0%, p = 0.002).; Conclusion: More research is needed to formulate guidelines for prevention, early detection and treatment of BV during pregnancy to reduce intrauterine inflammation and the associated adverse fetal outcomes.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Ng, Chuah, Cheah, Mohamed Ismail, Tan, Wong and Lim.)

Ng Cecilia, H. M., et al. (2023). "Establishing the Australian National Endometriosis Clinical and Scientific Trials (NECST) Registry: A protocol paper." Reproduction & fertility.
	Endometriosis is a common yet under-recognised chronic inflammatory disease, affecting 176 million women, trans and gender diverse people globally. The National Endometriosis Clinical and Scientific Trials (NECST) Registry is a new clinical registry, collecting and tracking diagnostic and treatment data, and patient-reported outcomes on people with endometriosis. The registry is a research priority action item from the 2018 National Action Plan for Endometriosis and aims to provide, large-scale, national and longitudinal population-based data on endometriosis. Working groups (consisting of patients with endometriosis, clinicians and researchers) developing the NECST Registry data dictionary and data collection platform started in 2019. Our data dictionary was developed based on existing and validated questionnaires, tools, meta-data and data cubes - World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHect), endometriosis CORE outcomes set, patient-reported outcome measures, the International Statistical Classification of Diseases-10th Revision Australian Modification diagnosis codes, and Australian Government datasets: Australian Institute for Health and Welfare (for sociodemographic data), Medicare Benefits Schedule (MBS; for medical procedures) and the Pharmaceutical Benefits Scheme (PBS; for medical therapies). The resulting NECST Registry is an online, secure cloud-based database; prospectively collecting minimum core clinical and health data across eight patient and clinician modules and longitudinal data tracking disease life course. The NECST Registry has ethics approval (HREC/62508/MonH-2020) and is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12622000987763).

Ng, K. Y. B., et al. (2021). "Smartphone-based lifestyle coaching modifies behaviours in women with subfertility or recurrent miscarriage: a randomized controlled trial." Reproductive Biomedicine Online 43(1): 111-119.
	RESEARCH QUESTION: Is an online lifestyle coaching platform more effective at modifying periconceptional behaviours than standard advice offered by the UK National Health Service (NHS)? DESIGN: Women with subfertility or recurrent miscarriage were recruited to a two-centre randomized controlled trial. They were randomized to either the online lifestyle coaching platform Smarter Pregnancy (intervention) or periconceptional advice provided by NHS websites (control). Participants completed a lifestyle questionnaire at baseline, 6, 12, 18 and 24 weeks, and the results were used to tailor lifestyle coaching in the intervention group. At baseline, 12 and 24 weeks, composite risk scores (CRS) were calculated. A lower CRS corresponds to a healthier lifestyle. RESULTS: Of the 400 women recruited, 262 women were randomized (131 in each arm). At 12 weeks, a reduction in CRS (includes risk score for intake of folic acid, vegetables and fruits, smoking and alcohol) was observed in the intervention versus control arms. After correcting for baseline, the difference in the CRS between intervention and control was -0.47 (95% CI -0.97 to 0.02) at 12 weeks and -0.32 (95% CI -0.82 to 0.15) at 24 weeks. A statistically significant reduction in lifestyle risk scores was found in women with a body mass index (BMI) of 25 kg/m2 or above compared with those with a BMI below 25kg/m2. The odds of being pregnant at 24 weeks was increased in the intervention versus control (OR 2.83, 95% CI 0.35 to 57.76). CONCLUSIONS: The Smarter Pregnancy coaching platform is more effective in delivering lifestyle advice and modulating behaviours to support women with a history of subfertility or recurrent miscarriage than standard online NHS advice.

Ng, S. M., et al. (2021). "Physical activity, confidence and quality of life among cancer patient-carer dyads." Sports medicine - open 7(1).
	Background: Physical activity (PA) has been positively associated with health‐related quality of life (HRQoL) among cancer patients and family caregivers. However, there has been no relevant research for patient‐caregiver dyads. Methods: Path analysis, based on the actor–partner interdependence model (APIM), was used to examine the relationship between physical activity and health‐related quality of life and explore the mediating role of emotional distress in 233 dyads. Results: In both patients and caregivers, physical activity had a direct positive effect on physical quality of life (QoL) but not on mental. There was a significant indirect effect of physical activity on health‐related quality of life via emotional distress for both dyad members. Patients’ and caregivers’ confidence in fighting cancer was negatively associated with their own emotional distress. Caregivers’ confidence in fighting cancer was positively associated with their physical activity and also negatively associated with patients’ emotional distress. Conclusions: Physical activity may be considered as a possible behavioral and rehabilitation strategy for improving health‐related quality of life in patient‐caregiver dyads and reducing negative symptoms. Future research and intervention may consider cancer patient‐family caregiver dyad as a unit of care.

Ng, T. Y., et al. (2022). "First in-human trial and prospective case series of an articulated laparoscopic camera system in minimally invasive surgery in gynecology: An IDEAL stage 1 and 2a study." BMJ Surgery, Interventions, and Health Technologies 4(1): e000117.
	Objectives Precision Robotics' Sirius Robotic Flexible Endoscopic System is a new, fully integrated, compact three-dimensional laparoscopic camera system with a disposable single-use flexible tip that can change its viewing direction. This IDEAL Stage 1 and 2a study assessed its safety, reliability and potential efficacy particularly for single incision laparoscopic surgery and vaginal natural orifice transluminal endoscopic surgery. Design Prospective single-institution, single-surgeon study. Setting The study was conducted in a multispecialty hospital. Participants Women aged 18-70 years scheduled for gynecological laparoscopic surgery were invited to participate. An information sheet and consent was available for the women and an informed consent was obtained. Thirteen participants completed this study. Interventions The laparoscopic procedures were done in the usual manner. The only difference was the Sirius System was used in place of the conventional laparoscope. All other procedures and instruments remained the same. Main outcome measures Primary outcome was the proportion of women who successfully completed the intended procedure using the Sirius System without conversion to another camera system, camera users and surgeon's view and experience, and iterations and modifications to the system. Secondary outcomes were the incidence of intraoperative and postoperative complications during the first 6 weeks following surgery, and duration of surgery. Results 85% (11/13) of women had their procedure completed successfully using the Sirius System. Two women required immediate conversion to the conventional laparoscope due to technical issues. There were no intraoperative complications. Users agreed that the improved field of view was beneficial for laparoscopic surgery. Iterative improvements were made in the imaging quality, user interface and manufacturing quality. Conclusions Sirius System has early indications for safety and efficacy for intermediate and major minimally invasive laparoscopic procedures in gynecology. Further studies are needed to confirm it can replace a conventional laparoscope in the surgical workflow. Trial registration number NCT05048407.Copyright © 2022 BMJ Publishing Group. All rights reserved.

Nguyen, D. B., et al. (2022). "Outpatient hysteroscopy is effective for uterine cavity evaluation following failed office-based endometrial biopsy." Journal of Obstetrics and Gynaecology Research 48(9): 2452-2458.
	Background: Failure to obtain an office-based endometrial biopsy for abnormal uterine bleeding is not uncommon. Although operating room-based procedures are traditionally considered the gold standard assessment tool in these circumstances, outpatient hysteroscopy is a less invasive, more cost-effective, and safer alternative. However, there is no contemporary Canadian literature on the effectiveness of an outpatient approach for this specific population. Objective(s): We aim to evaluate the effectiveness and outcomes of outpatient hysteroscopy for uterine cavity evaluation for patients who have failed an in-office endometrial biopsy attempt. Method(s): We conducted a retrospective cohort study of all patients referred to an academic outpatient hysteroscopy unit between January 2015 and January 2018, who underwent an outpatient hysteroscopy following failed endometrial biopsy. Data were collected from electronic medical records. Result(s): Of the 407 consecutive patients who underwent an outpatient hysteroscopic procedure, 68 met inclusion criteria. Postmenopausal bleeding was the most common indication for initial biopsy, and most failures were attributed to cervical stenosis. Outpatient hysteroscopies were successfully completed in 96% of cases (n = 65/68). Failure resulted from either anxiety and discomfort (n = 2), or severe intrauterine adhesions (n = 1). Overall, 10% of patients subsequently required an operating room-based hysteroscopy, either to complete a myomectomy or polypectomy, or to allow general anesthesia. Outpatient hysteroscopy identified endometrial hyperplasia and cancer in 4.5% and 3% of patients, respectively. Conclusion(s): Outpatient hysteroscopy following unsuccessful office endometrial biopsy attempts appears to be a feasible, safe, and cost-effective investigation strategy that may prevent the need for an operating room-based procedure in 90% of cases.Copyright © 2022 Japan Society of Obstetrics and Gynecology.

Nguyen Julie My, V., et al. (2022). "Dual mechanical and pharmacological thromboprophylaxis decreases risk of pulmonary embolus after laparotomy for gynecologic malignancies." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(1): 55-61.
	Objectives: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus.; Methods: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin.; Results: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss.; Conclusion: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Nguyen, K., et al. (2023). "A Prospective Study of Bladder Function Following Endometriosis Surgery with up to 8 years Follow-up." Journal of Minimally Invasive Gynecology.
	Study Objective: To assess long-term urinary function for women having laparoscopic surgery for endometriosis.; Design: Institutional Review Board-approved nested cohort study within a larger randomized controlled trial assessing urinary function following any benign laparoscopy for gynecological presentations.; Setting: Two tertiary-level university-affiliated hospitals.; Patients: Women with histologically confirmed endometriosis within the randomized controlled trial between April 2012 and November 2019, where baseline urinary function was determined.; Interventions: Women with histologically confirmed endometriosis were contacted between February and October 2020, and urinary function was re-assessed.; Measurements and Main Results: Urinary function was assessed using validated questionnaires across the domains of filling, voiding, incontinence, and quality of life determined distant from surgery. Higher scores correlated with a greater severity of symptoms. From 518/711 (72.9%) women with histologically confirmed endometriosis, 289/518 (55.8%) consented to the nested study. At a mean of 50 months (range 12-103 months) post-operatively, 35 participants (12.1%) had sought treatment for bladder symptoms, and 81 participants (28.0%) reported at least one urinary tract infection since their index surgery. There was a significant worsening of symptoms for filling, voiding, incontinence, and quality of life pre-operative to post-operatively (2.27 vs 3.32, 0.93 vs 2.02, 1.06 vs 2.32, 0.83 vs 2.13 respectively, p <.001). There was no statistically significant difference in urinary questionnaire scores in participants with and without uterovesical endometriosis. There was no statistically significant difference in any parameter when comparing any revised American Society of Reproductive Medicine (rASM) stage of endometriosis. Participants who had post-operative urinary retention reported a higher mean voiding score than those who did not (3.24 vs 1.94, p = .017), while participants with post-operative urinary tract infection reported a higher mean frequency score than those who did not (5.17 vs 3.24, p = .016).; Conclusion: This study suggests a decline in urinary function over time following laparoscopic surgery for endometriosis that is not dependent on the severity or location of the disease. (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Nguyen Nancy, T., et al. (2022). "Time to completion of radiation treatment in locally advanced squamous cell carcinoma of the vulva and the impact on survival." Gynecologic Oncology 167(2): 159-166.
	Objective: To assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS).; Methods: The National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion.; Results: There were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040-6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of <7 days (unadjusted HR 1.183 [95%CI: 1.066-1.313], p = 0.0016). When delays extended to ≥14 days compared to <14 days there was increased hazard of death (unadjusted HR: 1.263 [95%CI:1.126-1.416], p < 0.0001). Survival improved for patients with <7 versus ≥7 days delay whether treatment was with RT (median OS: 34.9 months versus 21.6 months, p < 0.01) or CRT (Median OS:58 months versus 41.3 months, p < 0.01). Stage IVA disease was associated with the greatest increase in hazard of death (HR 1.759 [95%CI 1.517-2.039], p < 0.0001) compared to stage II.; Conclusion: Radiation completion with <7 days delay is associated with improved overall survival, independent of concurrent chemotherapy. This suggest that strategies to minimize delays in radiation are crucial in locally advanced vulvar cancer.; Competing Interests: Declaration of Competing Interest Rebecca A. Brooks disclosures include Speaker's bureaus for Astra Zeneca, Advisory board for Merck, Tempus, and GlaxoSmithKline, Evidence panel for American College of Obstetrics Gynecology and Society of Gynecologic Oncology. Mathew Ponzini and Machelle Wilson disclose that they were supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1 TR001860. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Nancy T. Nguyen, Xiao Zhao and Gary Leiserowitz have nothing to disclose. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nguyen, Q. C., et al. (2024). "Rosie, a Health Education Question-and-Answer Chatbot for New Mothers: Randomized Pilot Study." JMIR formative research 8: e51361.
	BACKGROUND: Stark disparities exist in maternal and child outcomes and there is a need to provide timely and accurate health information. OBJECTIVE: In this pilot study, we assessed the feasibility and acceptability of a health chatbot for new mothers of color. METHODS: Rosie, a question-and-answer chatbot, was developed as a mobile app and is available to answer questions about pregnancy, parenting, and child development. From January 9, 2023, to February 9, 2023, participants were recruited using social media posts and through engagement with community organizations. Inclusion criteria included being aged ≥14 years, being a woman of color, and either being currently pregnant or having given birth within the past 6 months. Participants were randomly assigned to the Rosie treatment group (15/29, 52% received the Rosie app) or control group (14/29, 48% received a children's book each month) for 3 months. Those assigned to the treatment group could ask Rosie questions and receive an immediate response generated from Rosie's knowledgebase. Upon detection of a possible health emergency, Rosie sends emergency resources and relevant hotline information. In addition, a study staff member, who is a clinical social worker, reaches out to the participant within 24 hours to follow up. Preintervention and postintervention tests were completed to qualitatively and quantitatively evaluate Rosie and describe changes across key health outcomes, including postpartum depression and the frequency of emergency room visits. These measurements were used to inform the clinical trial's sample size calculations. RESULTS: Of 41 individuals who were screened and eligible, 31 (76%) enrolled and 29 (71%) were retained in the study. More than 87% (13/15) of Rosie treatment group members reported using Rosie daily (5/15, 33%) or weekly (8/15, 53%) across the 3-month study period. Most users reported that Rosie was easy to use (14/15, 93%) and provided responses quickly (13/15, 87%). The remaining issues identified included crashing of the app (8/15, 53%), and users were not satisfied with some of Rosie's answers (12/15, 80%). Mothers in both the Rosie treatment group and control group experienced a decline in depression scores from pretest to posttest periods, but the decline was statistically significant only among treatment group mothers (P=.008). In addition, a low proportion of treatment group infants had emergency room visits (1/11, 9%) compared with control group members (3/13, 23%). Nonetheless, no between-group differences reached statistical significance at P<.05. CONCLUSIONS: Rosie was found to be an acceptable, feasible, and appropriate intervention for ethnic and racial minority pregnant women and mothers of infants owing to the chatbot's ability to provide a personalized, flexible tool to increase the timeliness and accessibility of high-quality health information to individuals during a period of elevated health risks for the mother and child. TRIAL REGISTRATION: ClinicalTrials.gov NCT06053515; https://clinicaltrials.gov/study/NCT06053515.

Nguyen Thuy Truong, A. and I. Demeestere (2023). "A Journey to Reach the Ovary Using Next-Generation Technologies." International Journal of Molecular Sciences 24(23).
	Although effective in terms of the chances of future live birth, the current methods for fertility preservation, such as oocyte, embryo, or ovarian tissue cryopreservation, cannot be offered to all cancer patients in all clinical contexts. Expanding options for fertility preservation is crucial to addressing the need to encompass all situations. One emerging strategy is pharmacoprotection, a non-invasive approach that has the potential to fill existing gaps in fertility preservation. In addition to the identification of the most effective therapeutic agents, the potential for off-target effects remains one of the main limitations of this strategy for clinical application, particularly when healthy ovarian tissue is targeted. This review focuses on the advances in pharmacoprotective approaches and the challenge of targeting the ovaries to deliver these agents. The unique properties of gold nanoparticles (AuNPs) make them an attractive candidate for this purpose. We discuss how AuNPs meet many of the requirements for an ideal drug delivery system, as well as the existing limitations that have hindered the progression of AuNP research into more clinical trials. Additionally, the review highlights microRNA (miRNA) therapy as a next-generation approach to address the issues of fertility preservation and discusses the obstacles that currently impede its clinical availability.

Ni, L., et al. (2019). "Low molecular weight heparin monotherapy for recurrent abortion with antiphospholipid system: A protocol of a systematic review." Medicine 98(8): e14619.
	Background: Previous clinical studies reported low molecular weight heparin (LMWH) monotherpay has been utilized for the treatment of recurrent abortion (RCA) with antiphospholipid system (APS). However, its efficacy is still inconclusive. This systematic review aims to assess its efficacy and safety for patients with RCA and APS.; Methods: A systematic literature search for article up to February 2019 will be conducted in 9 databases: Cochrane Library, EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Inclusion criteria are randomized control trials of LMWH monotherpay for patients with RCA and APS. The Cochrane risk of bias tool will be used to evaluate the methodological quality for each qualified study. The summary results will be showed by using fixed-effects and random-effects models for pooling the data based on the heterogeneity of included studies.; Results: This systematic review will assess the clinical efficacy and safety of LMWH monotherpay in treating RCA with APS. The primary outcome is pregnancy loss. The secondary outcomes include frequency of preterm delivery, live birth rates, maternal and fetal complications, as well as adverse events.; Conclusion: The findings of this study will summarize the present evidence to judge whether LMWH monotherpay is an effective therapy for patients with RCA and APS.; Dissemination and Ethics: The findings of this study will be published by through peer-reviewed journals. This study does not needs ethic documents, because it will not analyze individual patient data.; Systematic Review Registration: PROSPERO CRD42019121064.

Niazi, A. and M. Moradi (2021). "The Effect of Chamomile on Pain and Menstrual Bleeding in Primary Dysmenorrhea: A Systematic Review." International Journal of Community Based Nursing and Midwifery 9(3): 174-186.
	Background: Primary dysmenorrhea is characterized by pain during menstruation without any pelvic pathology. It is a common problem among females in their reproductive age which is caused by increased production of prostaglandin in the endometrium as one of leading causes. Chamomile extract ceases the production of prostaglandins and leukotrienes. The aim of this study was to systematically review the clinical trials to determine the effect of Chamomile on pain and menstural bleeding in primary dysmenorrhea.; Methods: Search process to find relevant articles was conducted on electronic Iranian (MagIran, SID) and international databases (Google Scholar, Science Direct, PubMed, ProQuest, Cochrane library, Scopus, Web of Science and EBSCO), using English keywords and Persian equivalents such a "Dysmenorrhea", "Pain", "Menstrual bleeding" and "Chamomil" without a time limit until March 2020. Irrelevant, duplicate, descriptive, or qualitative studies were excluded. To evaluate the quality of articles, we used the Cochran's Risk of Bias tool.; Results: Among124 articles found in the initial search, finally 7 clinical trials (with a sample size of 1033) were systematically examined. Two out of 7 studies examined the effect of Chamomile on the pain of primary dysmenorrhea, 2 studies on the effect of Chamomile on menstrual bleeding volume, and 3 on the effect of Chamomileon pain and menstural bleeding in primary dysmenorrhea.; Conclusion: Based on results of the most reviewed studies, Chamomile can be considered as an effective treatment for primary dysmenorrhea and reducing menstrual bleeding. (Copyright: © International Journal of Community Based Nursing and Midwifery.)

Nica, A., et al. (2024). "Robotic versus vaginal radical trachelectomy for reproductive-aged patients with early-stage cervical carcinoma: A multi-center cohort study." Gynecologic Oncology 185: 95-100.
	Background: A randomized non-inferiority trial showed worse survival in women with early-stage cervical cancer treated with radical hysterectomy by minimally invasive approach compared to laparotomy; the impact of surgical approach on survival following radical trachelectomy is unknown. Objective(s): To examine oncologic outcomes in women with early-stage cervical cancer who underwent robotic or vaginal radical trachelectomy at Canadian cancer centers with the highest volumes of radical trachelectomy procedures. Study design: Retrospective multi-centre cohort analysis which includes patients who had surgery between 2006 and 2019. Women with International FIGO 2009 stage IA-IB cervical cancer who underwent radical trachelectomy and lymph node assessment were grouped by surgical approach (vaginal versus robotic surgery). Result(s): A total of 197 patients were included from 4 regional referral centres. 56 women underwent robotic radical trachelectomy and 141 underwent vaginal radical trachelectomy. All patients had lymph node assessment by a minimally invasive technique. Median age was 32 years, median tumor size was 12 mm, and median depth of invasion was 5 mm. Recurrence-free survival was 97% in both groups at a median follow-up of 57 months. On multivariable analysis, after adjusting for previously chosen confounders (high risk pathologic criteria, tumor size, and LVSI) there was no statistically significant difference in PFS between the 2 groups (HR 2.1, 95%CI 0.3-7.1, p = 0.5). Tumor size larger than 2 cm (HR 9.4, 95%CI 2.8-26, p = 0.003) was the only variable predictive of recurrence. Conclusion(s): Survival outcomes were excellent in both cohorts of patients undergoing robotic vs. vaginal radical trachelectomy. The surgical approach was not significantly associated with risk of recurrence after adjusting for clinically important confounders.Copyright © 2024

Nica, A., et al. (2022). "Robotic versus vaginal radical trachelectomy for reproductive-aged women with early cervical cancer: a multi-center Canadian study (097)." Gynecologic Oncology 166(Supplement 1): S64-S65.
	Objectives: The LACC trial recently showed worse overall and progression-free survival in women with early-stage cervical cancer treated with radical hysterectomy by a minimally invasive approach compared to laparotomy. However, the impact of the surgical approach on survival following radical trachelectomy is yet to be elucidated. This study aimed to examine oncological outcomes among reproductive-aged women with early-stage cervical cancer who underwent vaginal or robotic radical trachelectomy in Canada. Method(s): A retrospective multi-center cohort study was conducted among patients who had surgery between January 2006 and December 2019. Women with FIGO stage IA-IB cervical cancer who underwent radical trachelectomy and lymph node assessment were grouped by surgical method (vaginal trachelectomy with laparoscopic lymph node assessment vs robotic surgery). Patients who received neoadjuvant chemotherapy and those treated with a simple trachelectomy or a cone biopsy were excluded. Result(s): A total of 148 patients were included from three large volume referral centers. Of them, 38 women underwent robotic radical trachelectomy, while the other 110 under went vaginal radical trachelectomy. All patients had lymph node assessment by a minimally invasive technique (robotic or laparoscopic). The median follow-up was 39 months. The median age was 32 years (IQR: 28-35), median tumor size was 10 mm (IQR: 5-18), and median depth of invasion was 5 mm (IQR: 3-8). FIGO stage distribution was 11% IA1, 28% IA2, 50% IB1, and 11% IB2. Histology distribution was 51% squamous cell carcinoma, 40% adenocarcinoma, and 9% adenosquamous carcinoma. Among patients, 27% had positive lymphovascular space invasion (LVSI), 9% had at least one positive metastatic lymph node, and 3% had positive margins. Eighty-six percent of patients did not require any adjuvant treatment, while 6% received chemotherapy, 2% pelvic radiation, and 6% concurrent chemotherapy and radiation. There were no statistically significant differences between patients who had vaginal or robotic radical trachelectomy with regards to age, tumor size, depth of invasion, FIGO stage, LVSI, or adjuvant treatment. Only 7% of patients had tumors of > 2 cm, which was similar in both groups. Patients who were treated with vaginal radical trachelectomy had a higher proportion of adenosquamous histology (13% vs 0%, p=0.008), and were more likely to have positive lymph nodes (13% vs 0%, p=0.003) or positive margins (4% vs 0%, p=0.12). Progression-free survival was 96.8%, with four documented recurrences, three in the vaginal trachelectomy group and one in the robotic group. Three out of the four recurrences met at least intermediate-risk criteria and received adjuvant therapy, while the fourth did not and recurred centrally in the uterus. Conclusion(s): Survival for women who underwent radical trachelectomy in Canada in the last 15 years is very good regardless of surgical modality. Although our power is limited, we have shown that oncologic outcomes are favorable in this carefully selected low-risk population, standing in agreement with findings of other large retrospective series of patients treated with radical trachelectomy.[Formula presented]Copyright © 2022 Elsevier Inc.

Nica, A., et al. (2022). "Pre-operative wait times in high-grade non-endometrioid endometrial cancer: Do surgical delays impact patient survival?" Gynecologic Oncology 164(2): 333-340.
	Objective: Practice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients. Method(s): This was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS). Result(s): We identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1-7 days, 95% CI 1.61-4.51, and HR death 1.96 for 8-14 days, 95% CI 1.50-2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46-60 days, 95% CI 1.04-1.36, and HR death 1.42 for 61-75 days, 95% CI 1.11-1.83). Conclusion(s): Regionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival.Copyright © 2021 Elsevier Inc.

Nicholas, A. and M. Ghea (2023). "Perioperative vaginal misoprostol vs intraoperative pericervical hemostatic tourniquet in reducing blood loss during abdominal myomectomy: A Systematic Review and Meta-Analysis."
	
Nicklas, J. M., et al. (2024). "The Fit After Baby randomized controlled trial: an mHealth postpartum lifestyle intervention for women with elevated cardiometabolic risk." PloS One 19(1): e0296244.
	BACKGROUND: Postpartum women with overweight/obesity and a history of adverse pregnancy outcomes are at elevated risk for cardiometabolic disease. Postpartum weight loss and lifestyle changes can decrease these risks, yet traditional face‐to‐face interventions often fail. We adapted the Diabetes Prevention Program into a theory‐based mobile health (mHealth) program called Fit After Baby (FAB) and tested FAB in a randomized controlled trial. METHODS: The FAB program provided 12 weeks of daily evidence‐based content, facilitated tracking of weight, diet, and activity, and included weekly coaching and gamification with points and rewards. We randomized women at 6 weeks postpartum 2:1 to FAB or to the publicly available Text4baby (T4B) app (active control). We measured weight and administered behavioral questionnaires at 6 weeks, and 6 and 12 months postpartum, and collected app user data. RESULTS: 81 eligible women participated (77% White, 2% Asian, 15% Black, with 23% Hispanic), mean baseline BMI 32±5 kg/m2 and age 31±5 years. FAB participants logged into the app a median of 51/84 (IQR 25,71) days, wore activity trackers 66/84 (IQR 43,84) days, logged weight 17 times (IQR 11,24), and did coach check‐ins 5.5/12 (IQR 4,9) weeks. The COVID‐19 pandemic interrupted data collection for the primary 12‐month endpoint, and impacted diet, physical activity, and body weight for many participants. At 12 months postpartum women in the FAB group lost 2.8 kg [95% CI ‐4.2,‐1.4] from baseline compared to a loss of 1.8 kg [95% CI ‐3.8,+0.3] in the T4B group (p = 0.42 for the difference between groups). In 60 women who reached 12 months postpartum before the onset of the COVID‐19 pandemic, women randomized to FAB lost 4.3 kg [95% CI ‐6.0,‐2.6] compared to loss in the control group of 1.3 kg [95% CI ‐3.7,+1.1] (p = 0.0451 for the difference between groups). CONCLUSIONS: There were no significant differences between groups for postpartum weight loss for the entire study population. Among those unaffected by the COVID pandemic, women randomized to the FAB program lost significantly more weight than those randomized to the T4B program. The mHealth FAB program demonstrated a substantial level of engagement. Given the scalability and potential public health impact of the FAB program, the efficacy for decreasing cardiometabolic risk by increasing postpartum weight loss should be tested in a larger trial.

Nico, E., et al. (2022). "Patient Satisfaction of the Non-Surgical Lysis Procedure for Clitoral Adhesions in Patients with and without Lichen Sclerosuas." Journal of Sexual Medicine 19(Supplement 3): S24.
	Introduction Lichen sclerosus (LS) is a chronic, inflammatory skin disorder in the anogenital region typically found in prepubertal or postmenopausal women that causes skin thinning, whitening, wrinkling, itching, and pain. LS is an established risk factor for the development of clitoral adhesions (CA). CA occur when the prepuce adheres to the glans clitoris leading to discomfort, hypersensitivity/hyposensitivity, difficulty reaching orgasm, and chronic vulvodynia. However, CA can also occur in the absence of LS. Two lysis of CA treatment modalities exist - one surgical procedure and one non-surgical, office-based procedure that stretches the preputial tissue open. Previous studies explored LS patient satisfaction with surgical lysis or dorsal-slit surgery but not with the non-surgical approach. The non-surgical office-based procedure has also never been studied in patients without LS. Objective The aim of this study is two-fold: to evaluate patient satisfaction and outcomes of the non-surgical lysis of CA procedure in women with LS and to compare the efficacy of the procedure in patients with and without LS.Methods 61 women who have been treated for CA using the non-surgical lysis procedure at one sexual medicine practice from 2017-2021 were identified using a retrospective chart review. An online survey was sent to these patients to evaluate the efficacy of the procedure in improving pain and sexual functioning, as well as patient satisfaction with the procedure. Results 41 women participated in the study (67% response rate) and 5 had a diagnosis of LS that was optimally treated with highpotent steroids. In terms of procedure satisfaction, there was no significant difference in patient satisfaction (80% vs 83%) or the likelihood of recommending the procedure to a friend who also had CA (80% vs. 94%) among women with and without LS. In regards to improving sexual functioning, there was no significant difference in the procedure's ability to improve sexual arousal (80% vs. 60%), ability to orgasm (80% vs. 62%), and sexual satisfaction (60 vs. 72%) between women with and without LS. Finally, there was no significant difference in reporting the procedure was painful (40% vs. 25%) or the incidence of recurrence of adhesions (40% vs. 51%). Conclusions This study demonstrates high patient satisfaction and improvement in sexual functioning associated with the nonsurgical lysis procedure for CA in women with and without LS. CA should not be considered as an adjunct side-effect of LS but as an independent pathology. Physicians should examine the clitoris in women with and without LS in order to determine if a patient has CA. Once diagnosed, the non-surgical lysis procedure has similar efficacy and patient satisfaction in women with and without LS and could be considered as a treatment option for improving sexual function in women.

Nicola, M., et al. (2022). "Effectiveness of rehabilitative interventions in patients with vulvodynia: a systematic review of the literature."
	
Nicolás, I., et al. (2022). "Impact of SARS-COV2 Pandemic on Patients with Endometriosis and Their Health Care." Journal of women's health (2002) 31(4): 480-486.
	Background: Endometriosis is a debilitating chronic inflammatory disease. The current SARS-COV2 pandemic has had an impact on the management of these patients. Tele-health care has been a relevant tool. The aim of this study was to analyze the impact of the SARS-COV2 pandemic on the perceived clinical health status and the type of care received in patients with endometriosis. Materials and Methods: We evaluated 945 premenopausal women treated at the Hospital Clinic of Barcelona between October 1 and December 31, 2020. Five hundred forty-nine women had endometriosis, and 396 had other benign gynecological diseases. An online health survey was sent to these patients. Clinicopathological features data were recorded. Results: Compared to patients with other benign gynecological diseases, a higher proportion of patients with endometriosis reported worsening of their symptoms (148/549, 27% vs. 85/396, 21.5%) and concern about their disease (515/549, 93.8% vs. 342/396, 86.4%), and more frequently received tele-health care (73.8% vs. 54.0%) during the pandemic. Patients with endometriosis and "significant" pelvic pain reported more concern and worsening than patients without "significant" pelvic pain, and evaluated the assistance received poorly. Multivariate analysis showed pelvic pain, limitation in usual activity, and sadness as risk factors of perception of disease worsening. Awaiting surgery and the feeling of sadness were risk factors of concern. Conclusions: Patients with endometriosis, and especially patients with "significant" pelvic pain, reported greater concern and the perception of worsening during the SARS-COV2 pandemic. Tele-health is a useful tool in patients with endometriosis, and face-to-face visit should be considered in those reporting "significant" pelvic pain. Clinical Trial Registration Number: HCB 1202011497.

Nicolas-Boluda, A., et al. (2024). "Developing a set of patient-centered outcomes for routine use in endometriosis: An international Delphi study." Acta Obstetricia et Gynecologica Scandinavica 103(1): 138-152.
	Introduction: There is large variation in individual patient care for endometriosis. A uniform approach to measure outcomes could be incorporated into routine clinical practice to personalize and monitor treatments and potentially improve the quality of care. The aim of this study is to identify a group of patient-centered outcomes for use in routine endometriosis care which are relevant to all patient profiles.; Material and Methods: By means of a modified two-round Delphi study with international representation including healthcare professionals, researchers and patient representatives (51 participants, 16 countries) we developed a set of patient-centered measurements. The participants evaluated 47 Patient Reported Outcome Measures (PROMs) and 30 Clinician Reported Outcome Measures (CROMs) regarding their feasibility and relevance for their use in routine endometriosis care. After the two rounds of quotation, meetings of the experts were convened to participate in a final discussion to finalize the consensus of the final set of included measures.; Results: The final set of patient-centered outcomes includes six PROMs (measuring symptomatic impact, pain, work productivity and quality of life) and 10 CROMs (measuring clinical, imaging and surgical indicators). A supplementary list of outcomes was added to include important dimensions that were considered essential by the expert panel but are not relevant to all patients. In addition the need for development of specific tools (PROMs) measuring the psychological impact and the impact in sexual activity of endometriosis was highlighted.; Conclusions: We have developed a set of patient-centered outcomes measures in endometriosis care. The selected outcomes comprise the common features for all patients suffering from endometriosis. adapted for use in routine practice. The list of outcomes has been adapted for use in routine practice from which clinicians can chose, depending on their needs. (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Nicole Fleck, C., et al. (2021). "Micronutrient Supplementation and Female Fertility: A Systematic Review."
	
Nicole, K., et al. (2022). "Synthetic versus absorbable sutures for surgical repair of apical pelvic organ prolapse in women: A systematic review." PROSPERO International prospective register of systematic reviews.
	
Nicolson, S., et al. (2022). "Supporting early infant relationships and reducing maternal distress with the Newborn Behavioral Observations: A randomized controlled effectiveness trial." Infant mental health journal 43(3): 455-473.
	Research points to the significant impact of maternal distress on the parent-infant relationship and infant development. The Newborn Behavioral Observations (NBO) is a brief intervention supporting the infant, the parent and their relationship. This randomized controlled trial examined the effectiveness of the NBO in a population with antenatal distress and risk of postnatal depression (PND). Pregnant, first-time mothers with current anxiety or depression symptoms or past mental illness were recruited from two Australian hospitals. Participants received three NBO sessions in the first month of life plus treatment as usual (TAU), or, TAU-only. Outcomes assessed at infant age 4 months included mother-infant interaction quality; maternal anxiety and depression symptoms; and depression diagnosis. Of 111 pregnant individuals randomized, 90 remained eligible and 74 completed the trial (82.2% retention). There were intervention effects on emotional availability F(6, 67) = 2.52, p = .049, Cohen's d = .90, with higher sensitivity and non-intrusiveness in the intervention group (n = 40) than the comparison group (n = 34). There was an intervention effect approaching significance for anxiety symptoms at 4 months (p = .06), and a significant effect over time (p = .014), but not for depression symptoms. Anxiety and depression symptoms significantly reduced to sub-clinical levels within the intervention group only. There were fewer depression diagnoses (n = 6) than expected across groups, with no observed intervention effect. No adverse intervention effects were seen. Exploratory analysis of sensory processing sensitivity suggested differential susceptibility to distress and intervention benefits. The NBO was accepted and exerted meaningful effects on relationship quality and distress; and may enhance the infant's interaction experience and maternal emotional adjustment in at-risk populations. (© 2022 The Authors. Infant Mental Health Journal published by Wiley Periodicals LLC on behalf of Michigan Association for Infant Mental Health.)

Nicum, S., et al. (2021). "Randomised phase II trial of olaparib compared to weekly paclitaxel or olaparib plus cediranib in patients with platinum-resistant ovarian cancer (OCTOVA)." Annals of Oncology 32: S725‐S726.
	Background: The main aims of the OCTOVA trial were to compare the efficacy and toxicity of olaparib (O) with weekly paclitaxel (wP) and also the oral combination of olaparib plus cediranib (O+C) in recurrent ovarian cancer (OC). Methods: Participants with high grade ovarian, fallopian tube, primary peritoneal cancer who relapsed within 12 months of previous platinum‐based therapy were randomised, with stratification for germline BRCA1/2 mutation status, prior PARP inhibitor (PARPi) or anti‐angiogenic therapy, to receive O (300mg daily) or either wP (80mg/m2 d1,8,15, q28) or O+C (300mg/20mg daily respectively). Treatment continued until disease progression or unacceptable toxicity. Primary endpoint was Progression Free Survival (PFS). Secondary endpoints were safety and tolerability of the combination of O+C, overall survival, objective response rate, and quality of life. A sample size of 138 (46 per arm) was sufficient to observe HR 0.64 in favour of O+C compared to O alone and 1.44 for wP compared to O (20% one‐sided type I error, 80% power, 15% dropout, one‐sided p‐value <0.2). Results: OCTOVA recruited 139 participants, median 65 years (IQR:38‐84), from 15 UK centres over 34 months. 31 (22%) had had prior PARPi therapy, 47 (34%) prior anti‐angiogenic therapy. 41 (29%) had known germline BRCA1/2 mutations. 125 (90%) had relapsed <6 months after prior platinum. Median 2 prior lines of chemotherapy (range 1‐7). There was no difference in PFS between wP and O (HR=0.97, 60%CI: 0.79, 1.19; p=0.55). PFS was increased for O+C compared to O (HR=0.70; 60%CI: 0.57, 0.86; p=0.08). There were 239, 176, and 137 treatment related adverse events (all grades) in the O+C, wP and O arms respectively. Conclusions: The OCTOVA trial demonstrated that the combination of O+C showed greater efficacy than O alone, but we did not find evidence that wP was inferior to O in women with multiply relapsed OC. Clinical trial identification: ISRCTN14784018, NCT03117933. Legal entity responsible for the study: University of Oxford. Funding: AstraZeneca. Disclosure: S. Nicum: Financial Interests, Other, Advisory and speaker honoraria, travel expenses: GSK; Financial Interests, Other, Advisory and speaker honoraria, travel expenses: Tesaro; Financial Interests, Other, Advisory and speaker honoraria, travel expenses: Roche; Financial Interests, Other, Advisory and speaker honoraria: Abbvie; Financial Interests, Other, Advisory and speaker honoraria: Clovis; Financial Interests, Other, Advisory and speaker honoraria, travel expenses and peer‐reviewed research funding: AstraZeneca. I. McNeish: Financial Interests, Advisory Board, Advisory Board and institutional funding: AstraZeneca; Financial Interests, Advisory Board: GSK; Financial Interests, Advisory Board: Clovis Oncology; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Scancell. R.M. Glasspool: Financial Interests, Advisory Board, Advisory boards speaker fees: AstraZeneca; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board, Advisory boards speaker fees: Clovis; Financial Interests, Advisory Board, Advisory boards speaker fees: GSK/Tesaro; Financial Interests, Other, Consultacy fees: Sotio; Financial Interests, Advisory Board: Immunogen; Financial Interests, Research Grant, Investigator Initiated Trial Grant: Clovis; Financial Interests, Principal Investigator, Site PI for commercially sponsored trials: Clovis; Financial Interests, Principal Investigator, Site PI for commercially sponsored trials: AstraZeneca; Financial Interests, Principal Investigator, Site PI for commercially sponsored trials: GSK; Financial Interests, Principal Investigator, Site PI for commercially sponsored trials: Immunogen; Financial Interests, Research Grant, Investigator Initiated Trial Grant: Boehringer Ingelheim; Financial Interests, Research Grant, Investigator Initiated Trial Grant: Lilly/Ignyta; Financial Interests, Principal Investigator, Site PI for commercially sponsored trials: Lilly/Ignyta; Financial Interests, Other, Consultacy fee or trial streeing committee: Novartis; Financial Interests, Leadership Role: NCRI Ovarian Group Chair; Financial Interests, Leadership Role: SGCTG Ovarian lead; Financial Interests, Leadership Role: IGCS council member; Financial Interests, Leadership Role: ESMO Gyn Cancer Faculty; Financial Interests, Leadership Role: GCIG Meta‐Analysis Group Chair; Financial Interests, Leadership Role: ENGOT early phase Co‐Chair; Financial Interests, Leadership Role: Horizons Study Expert Panel member; Financial Interests, Leadership Role: Target Ovarian Cancer Scientific Advisory Board. M. Hall: Financial Interests, Research Grant, Clinical Trial grants: BMS; Financial Interests, Research Grant, Clinical Trial grants: Merck; Financial Interests, Invited Speaker, grants and personal fees: Clovis Oncology; Financial Interests, Invited Speaker, personal fees for Advisory Boards and educational roles GSK; Financial Interests, Invited Speaker, personal fees for Advisory Boards and educational roles: Amgen; Financial Interests, Invited Speaker, personal fees for Advisory Boards and educational roles: Roche; Financial Interests, Invited Speaker, personal fees for Advisory Boards and educational roles: AstraZeneca. A. Michael: Financial Interests, Advisory Board: Clovis; Financial Interests, Advisory Board: ESAI; Financial Interests, Advisory Board: Ipsen; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Tesaro; Financial Interests, Advisory Board: GSK. S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Oncxerna; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Invited Speaker: Takeda. G. Jayson: Financial Interests, Institutional, Research Grant: AstraZeneca. A. Clamp: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.

Nielson, C. M., et al. (2021). "Relative Dose Intensity of Chemotherapy and Survival in Advanced Stage Solid Tumor Cancer Patients: A Systematic Review and Meta-Analysis." The Oncologist.
	BACKGROUND: Chemotherapy-induced toxicities lead to therapy dose reduction or delay affecting patient outcomes. This systematic review and meta-analysis evaluated the impact of relative dose intensity (RDI) on survival in adult solid-tumor cancer patients on nonadjuvant-based chemotherapy regimens. METHODS: PubMed, Embase, and Web of Science databases were searched for peer-reviewed English journal articles or congress abstracts evaluating association between RDI and survival; observational studies, case series of ≥20 patients, and clinical trials published between 2013─2020 were eligible. Meta-analyses were conducted to quantify the association between RDI levels and overall survival (OS) among studies reporting a hazard ratio (HR) for OS by similar tumor types, regimens, and RDI. Forest plots represented summary HR and 95% confidence interval (CI); Cochran's Q and I2 tests evaluated study heterogeneity. RESULTS: Overall, 914 articles were reviewed and 37 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80 vs ≥80% and <85% vs ≥85% was observed upon meta-analysis of four carboplatin-based studies for breast, non-small cell lung, or ovarian cancer (HR 1.17; 95% CI: 1.07-1.27), and three FOLFOX-/FOLFIRI/FOLFIRINOX-based studies for colorectal or pancreatic cancer (HR 1.39; 95% CI: 1.03-1.89). Grade 3 or higher hematologic toxicities were higher for carboplatin-based regimens (thrombocytopenia: 14-22%; anemia: 15-19%; neutropenia: 24-58%) than FOLFOX-/FOLFIRI/FOLFIRINOX-based regimens (thrombocytopenia: 1-4%; anemia: 5-19%; neutropenia: 19-47%). CONCLUSION: The results suggested longer OS with RDI ≥80 or ≥85% for both regimens, indicating that management of toxicities across treatment modalities may contribute to maintenance of higher RDI and benefit survival for patients with advanced solid tumors. IMPLICATIONS FOR PRACTICE: Chemotherapy-induced toxicities lead to dose reduction and/or treatment delay , thus affecting patient outcomes. Results of this systematic review and meta-analysis, evaluating the impact of relative dose intensity (RDI) on survival in solid tumor cancer patients on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for solid tumor cancer patients on carboplatin-based and FOLFOX-/FOLFIRI/FOLFIRINOX-based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80 or ≥85%. While grade 3 or higher hematologic toxicities occurred more in carboplatin-based studies, managing toxicities across treatment regimens may contribute to maintenance of higher RDI and ultimately benefit overall survival.

Nierengarten Mary, B. (2023). "Combination therapy may create a practice change for advanced or recurrent endometrial cancer: Two new studies show the value of adding immunotherapy to standardof-care chemotherapy to improve progression-free survival." Cancer 129(17): 2600-2601.
	
Nierengarten Mary, B. (2023). "FDA grants accelerated approval for targeted therapy for platinum-resistant gynecologic cancers." Cancer 129(5): 656.
	
Nierengarten Mary, B. (2023). "New standard of care for platinum-resistant ovarian cancer." Cancer 129(17): 2601-2602.
	
Nieto, K., et al. (2023). "Improving Complex Brachytherapy Efficiency in the Current Financial Climate." International journal of radiation oncology biology physics 117(2 Supplement): e422-e423.
	Purpose/Objective(s): To optimize multidisciplinary collaboration in the setting of limited resources to increase the efficiency of complex brachytherapy workflow for patients with locally advanced cervical cancer. Materials/Methods: High Dose Rate (HDR) brachytherapy is a critical component in the treatment of women with locally advanced cervical cancer. The completion of HDR brachytherapy to provide a complete treatment of concurrent chemoradiation and brachytherapy of <56 days has been well established. A quality improvement (QI) initiative was born out of the need to accommodate an increasing volume of patients with locally advanced cervical cancer. The challenges addressed were: different location of the operating room (OR), HDR brachytherapy suite, MR scanner; Inconsistent OR days; Post-Anesthesia Care Unit (PACU)/transportation delays; Anesthesiology staffing constraints. The QI initiative required multidisciplinary collaboration. A new protocol was finalized which provided protected OR time, and changed analgesia from general anesthesia requiring prolonged monitoring in PACU, to a pre-procedural epidural with moderate sedation. Additionally, a dedicated anesthesiologist was assigned to discuss process improvement, and the medical history for these complex patients as it relates to anesthesia safety. The streamlined process allows the patients' physical time in PACU to be bypassed; a dedicated brachytherapy nurse competent in moderate sedation recovery accompanies the patient to CT simulation. An MR protocol was established with tentative slots secured. The primary metric was the change in the number of interstitial cases performed. Additional metrics included: total case time, anesthesiology delay, MR delay, and number of OR days where 2 complex cases are performed. Result(s): Prior to initiation of QI initiative, from 01/2022-09/2022 there were 27 cases, average 3.0/month. After implementation of QI project, from 10/2022-02/2023 there were 32 cases, average 6.4/month, a 113.3% increase. Total case time decreased from baseline 9.3 hours to average 6 hours (Range: 3.8-10.6). Anesthesiology related delays were on average 18.5 minutes (Range: -15-35). MR related delays were on average 87.6 minutes (Range: 35-275). These changes now permit the flexibility of performing 2 complex interstitial cases per day, instead of one. The average days per month where two interstitial cases are performed increased from 0.4 to 1.4. Conclusion(s): As hospital systems continue to face economic constraints, it is critical that we leverage our existing resources in order to provide timely care to our patients. This QI initiative shows that despite the limitation in brachytherapy operations, systems can be changed through multidisciplinary collaboration to improve efficiencies and increase capacities while working within financial workforce constraints to provide optimal patient care.Copyright © 2023

Nieuwenhuyzen-de Boer, G., et al. (2021). "Improvement of complete cytoreduction for advanced-stage ovarian cancer with adjuvant use of the plasmajet device. results of a rct." International Journal of Gynecological Cancer 31(SUPPL 1): A221‐.
	Results of the PlaComOv‐study, a randomized, controlled trial in the Netherlands Introduction/Background The most important prognostic factor for patients with advanced‐stage ovarian cancer is complete cytoreductive surgery (CRS). Standard surgical treatment with electrosurgery cannot always result in complete CRS, especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of the PlasmaJet® Device will help increase the complete cytoreduction rate. Methodology 327 patients with FIGO stage IIIB‐IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were assigned to either surgery with PlasmaJet (intervention) or without PlasmaJet (control group). Primary outcome was the percentage of complete CRS. Secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30 daymorbidity and quality of life (QoL). Result(s) Complete CRS was achieved in 119 patients (75.8%) of the intervention group and in 115 patients (67.6%) of the control group (P=0.131). A per‐protocol analysis was performed in which data of 27 patients with unresectable disease were excluded, considering that the aim of the study was to examine the effectiveness of the use of the PlasmaJet in achieving CRS. Complete CRS was obtained in 85.6% in the intervention group and in 71.5% in the control group (absolute difference 14.1%, 95% confidence interval [CI], 0.047 to 0.230; P=0.005). The number of colostomies was lower in the intervention group (6.5% versus 12.7%) but did not differ significantly (P=0.169). Patient‐reported QoL six months after surgery differed between groups in favor of PlasmaJet surgery (95% CI, 0.455 to 8.350; P=0.029). Other secondary outcomes did not differ significantly. Conclusion The adjuvant use of the PlasmaJet during CRS for advanced stage ovarian cancer resulted in a significant higher proportion of complete CRS in patients with resectable disease and a higher QoL six months after surgery.

Nieuwenhuyzen-de Boer Gatske, M., et al. (2023). "Cytoreductive Surgery with the PlasmaJet Improved Quality-of-Life for Advanced Stage Ovarian Cancer Patients." Cancers 15(15).
	Background: Knowledge of quality-of-life after cytoreductive surgery is important to counsel patients with advanced-stage epithelial ovarian cancer prior to surgery. The aim of this study was to determine whether the use of the PlasmaJet Surgical device during cytoreductive surgery has an effect on the quality-of-life of patients with advanced epithelial ovarian cancer.; Methods: Data included in this prospective observational study were derived from the PlaComOv study, in which patients with advanced epithelial ovarian cancer were randomly assigned to have cytoreductive surgery with or without adjuvant use of the PlasmaJet. Quality-of-life was measured before surgery and one, six, 12, and 24 months after surgery with three questionnaires: the EORTC QLQ-C30, QLQ-OV28, and EQ-5D-5L.; Results: Between 2018 and 2020, 326 patients were enrolled in the trial. The overall response rate was high, with the lowest response rate at 24 months of 77%. At 6 months, quality-of-life was higher in the intervention group (95%CI 0.009; 0.081, p = 0.045). At 12 months, quality-of-life was higher in the intervention group with fewer symptoms of fatigue, appetite loss, and diarrhea (95%CI 0.6; 10,0, p = 0.027); similarly, patients in the intervention group reported a better body image (95%CI -14.2; -3.0, p = 0.003) and a higher score on the visual analog scale (95%CI 1.99; 11.15, p = 0.005). At 24 months postoperatively, no further difference was found between the two groups except for pain (95%CI -12.9; -0.8, p = 0.027) and body image (95%CI -13.808; -0.733, p = 0.029). A higher quality-of-life in the intervention group was partially explained by the mediator 'surgery outcome'.; Conclusions: This study demonstrated knowledge of patients' quality-of-life until two years after cytoreductive surgery. The use of the PlasmaJet Surgical device during cytoreductive surgery leads to a higher quality-of-life than conventional surgery with electrocoagulation alone. Even after adjustment for the mediator of surgical outcome, a higher quality-of-life was seen in patients who had surgery with the use of the PlasmaJet device.

Nieuwenhuyzen-de Boer Gatske, M., et al. (2022). "Cost Study of the PlasmaJet Surgical Device Versus Conventional Cytoreductive Surgery in Patients With Advanced-Stage Ovarian Cancer." JCO clinical cancer informatics 6: e2200076.
	Purpose: Adjuvant use of Neutral Argon Plasma (PlasmaJet Surgical Device) during cytoreductive surgery (CRS) for advanced-stage epithelial ovarian cancer improves surgical outcomes. The aim of this study is to examine the costs of adjuvant use of the PlasmaJet during surgery compared with conventional CRS in advanced-stage epithelial ovarian cancer.; Materials and Methods: The patients were randomly assigned to surgery with or without the PlasmaJet. Analysis of the intra- and extramural health care costs was performed. Costs were divided into three categories: costs of the diagnostic phase (T1), inpatient care up to discharge including costs of surgery (T2), and outpatient care including chemotherapy until 6 weeks after the last cycle of chemotherapy (T3).; Results: Overall, 327 patients underwent CRS (surgery with PlasmaJet: n = 157; conventional surgery: n = 170). The mean total health costs were significantly higher for CRS with adjuvant use of PlasmaJet compared with conventional CRS (€19,414 v €18,165, P = .017). Costs are divided into costs of the diagnostic phase (€2,034 v €1,974, P = .890), costs of inpatient care (€10,956 v €9,556, P = .003), and costs of outpatient care (€6,417 v €6,628, P = .147).; Conclusion: Mean total health care costs of the use of PlasmaJet in CRS were significantly higher than those for conventional CRS. This difference is fully explained by the additional surgery costs of the use of PlasmaJet. However, surgery with the use of the PlasmaJet leads to a significantly higher percentage of complete CRS and a halving of stomas. A cost-effectiveness analysis will be performed once survival data are available (funded by ZonMw, Trial Register NL62035.078.17).

Niino Clarissa, A., et al. (2023). "Bladder instillation patterns in a cohort of women with interstitial cystitis/bladder pain syndrome." Urogynecology (Philadelphia, Pa.) 29(11): 914-919.
	Purpose: To determine intravesical instillation patterns among women receiving treatment for interstitial cystitis/bladder pain syndrome (IC/BPS).; Methods: Using the Veterans Affairs Informatics and Computing Infrastructure, active female users of the Veterans Affairs system with an ICD-9 diagnosis of IC/BPS (595.1) were randomly sampled. Patients were considered to have IC/BPS (by chart review) if they had two visits complaining of bladder-centric pain in the absence of positive urine culture ≥6 weeks apart or history of bladder pain with one additional visit for bladder-centric pain. We abstracted the dates of intravesical instillations for each patient. A "course" of instillations was defined as ≥1 instillations made with <21 days between visits.; Results: We identified 641 women with confirmed diagnosis of IC/BPS, 78 of whom underwent a total of 344 intravesical instillations. On average each subject had 1.5 +/- 0.8 courses between October 2004-July 2016. Each course was an average of 3.1 +/- 2.6 instillations. 55% of courses consisted of one instillation. Only 22% of courses had 6 or more instillations, the number typically recommended to achieve clinical response. Each instillation within a course was an average of 9.4 +/- 4.0 days apart. Most instillations (77%) were a cocktail of two or more drugs.; Conclusions: In our cohort, few women with IC/BPS received a recommended treatment course of six weekly instillations, with most receiving only one per course. Future studies are needed to determine if instillation courses were altered from the guideline due to provider practice patterns, early improvement, or poor tolerance of instillations.; Competing Interests: Conflict of Interest Discloser: The authors have no relevant conflicts of interest to disclose.

Nikolaos, P. and H. Dimitrios (2022). "The use of platelet-rich plasma for gynecological disorders: a systematic review."
	
Nikolaos, P., et al. (2021). "The Effect of Low‐Intensity Shockwave Therapy on Lower Urinary Tract Symptoms: A Systematic Review and Meta‐Analysis."
	
Nikolopoulos, M., et al. (2022). "ROBOTIC SURGERY OUTCOMES IN A GYNAECOLOGICAL ONCOLOGY CANCER CENTRE." International Journal of Gynecological Cancer 32(Supplement 2): A196.
	Introduction/Background Robotic surgery (RS) in gynaecological oncology has been shown to overcome the limitations of conventional laparoscopy, improve perioperative outcomes and reduce length of stay (LOS). RS has lower conversion rates and shorter learning curve than laparoscopic surgery (LS). The blood loss is significantly less. RS is preferred in morbidly obese women. We share our experience of introducing RS at our centre and study its impact on our clinical outcomes and service. Methodology RS was introduced in December 2020 during COVID-19 pandemic. A second surgeon trained from September 2021. Data was collected prospectively recording indications, operating-time, blood loss, LOS and complications. Outcomes were compared with the Hospital Episode Statistics (HES) data and cost analysed. Results Until May 2022, 143 cases underwent RS using da Vinci- Si, X or Xi robots. Most women (84) had endometrial cancer. Complexity of surgery increased in latter half with women with BMI>40kg/m2 (23), large fibroid uterus(22), ovarian cancer staging(12) and radical hysterectomy(3). Median docking time was eight minutes, median operating-time was 150 minutes and median blood loss was 50 mls. Average LOS was 1.8 days and median LOS 1 day(range 0-6 days). Average LOS for LS was 3 days and open abdominal surgery 8.6 days. Minor complications(11) were treated conservatively. Two patients with adhesions had bladder injury. One surgery was converted to open abdominal surgery during the early learning phase. Introduction of robotic surgery increased the minimalaccess surgery (MAS) rate by 15%. The operating-time showed decreasing trend with experience while surgical productivity {average number of cases per theatre list} remained the same. Conclusion There is a significant reduction in hospital stay and a clear cost benefit of robotic surgery. There is a significant increase in the MAS rates even during the early phase of learning with no increase in overall morbidity.

Nilsen, G., et al. (2024). "Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero." Acta Obstetricia et Gynecologica Scandinavica 103(1): 176‐187.
	Introduction: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre‐pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Material and methods: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z‐scores. Linear regression models were used to estimate the effect of metformin on offspring z‐scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S‐testosterone, s‐androstenedione, and s‐sex‐hormone binding globulin from four timepoints in pregnancy were analyzed. Results: Compared with the PCOS‐placebo group, newborns in the PCOS‐metformin group had larger head circumference (head circumference z‐score: mean difference = 0.25, 95% CI = 0.11– 0.40). This effect of metformin on head circumference z‐score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS‐phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS‐placebo group were shorter than in the reference population (birth length z‐score: mean = −0.04, 95% CI = –0.05 to −0.03), but head circumference and birthweight were similar. Conclusions: Larger head circumference was observed at birth in metformin‐exposed offspring of mothers with PCOS. PCOS‐offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight‐to‐height ratio at birth.

Nilsson, S., et al. (2023). "Resistance training decreased abdominal adiposity in postmenopausal women." Maturitas 176: 107794.
	Objective: To investigate if abdominal adipose tissue volumes and ratios change after a 15-week structured resistance training intervention in postmenopausal women with vasomotor symptoms (VMS).; Study Design: Sixty-five postmenopausal women with VMS and low physical activity were randomized to either three days/week supervised resistance training or unchanged physical activity for 15 weeks. Women underwent clinical anthropometric measurements and magnetic resonance imaging (MRI) at baseline and after 15 weeks. MRI was done using a Philips Ingenia 3.0 T MR scanner (Philips, Best, The Netherlands). The per protocol principle was used in the analysis of data.; Main Outcome Measurements: The absolute change from baseline to week 15 in visceral adipose tissue (VAT) volume and the relative ratio (VAT ratio) between VAT and total abdominal adipose tissue (TAAT), i.e. the sum of abdominal subcutaneous adipose tissue (ASAT) and VAT.; Results: There were no significant differences between the groups in characteristics, anthropometry or MRI measures at baseline. Women who were compliant with the intervention (i.e. participated in at least two of the three scheduled training sessions per week) had significantly different reduction over time in ASAT (p = 0.006), VAT (p = 0.002), TAAT (p = 0.003) and fat ratio (p < 0.001) compared with women in the control group.; Conclusions: Implementation of a 15-week resistance training regimen in midlife may help women to counteract the abdominal fat redistribution associated with the menopausal transition.; Clinical Trials: gov registered ID: NCT01987778.; Competing Interests: Declaration of competing interest Janne West and Magnus Borga are shareholders of AMRA Medical AB. No other competing interests exist among the authors. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Nilsson, S., et al. (2022). "Resistance training reduced luteinising hormone levels in postmenopausal women in a substudy of a randomised controlled clinical trial: A clue to how resistance training reduced vasomotor symptoms." PloS One 17(5): e0267613.
	Background: Vasomotor symptoms (VMS) are common around menopause. Menopausal hormone therapy is the most effective treatment for VMS. Physical exercise has been proposed as an alternative treatment since physically active women have previously been found to experience fewer VMS than inactive women. In our randomised controlled trial on resistance training to treat VMS, sympoms were reduced by 50% in the intervention group compared with the control group.; Objectives: To propose a mechanism to explain how resistance training reduced VMS and to assess if luteinizing hormone (LH) and follicle stimulating hormone (FSH) were affected in accordance with the proposed mechanism.; Trial Design and Methods: A substudy of a randomized controlled trial on 65 postmenopausal women with VMS and low physical activity who were randomised to 15 weeks of resistance training three times per week (n = 33) or to a control group (n = 32). To be regarded compliant to the intervention we predecided a mean of two training sessions per week. The daily number of VMS were registered before and during the 15 weeks. Blood samples were drawn for analysis of LH and FSH at baseline and after 15 weeks.; Results: LH decreased significantly in the compliant intervention group compared with the control group (-4.0±10.6 versus 2.9±9.0, p = 0.028 with Mann-Whitney U test). FSH also decreased in the compliant intervention group compared with the control group, however not enough to reach statistical significance (-3.5±16.3 versus 3.2±18.2, p = 0.063 with Mann-Whitney U test). As previously published the number of hot flushes decreased significantly more in the intervention group than in the control group but there was no association between change in LH or FSH and in number of VMS.; Conclusions: We propose that endogenous opiods such as β-endorphin or dynorphin produced during resistance training decreased VMS by stimulating KNDγ-neurons to release neurokinin B to the hypothalamic thermoregulatory centre. Through effects on KNDγ-neurons, β-endorphin could also inhibit GnRH and thereby decrease the production of LH and FSH. The significanty decreased LH in the compliant intervention group compared with the control group was in accordance with the proposed mechanism.; Competing Interests: The authors have declared that no competing interests exist.

Nilufer, A., et al. (2021). "Role of Macronutrients, Dairy Products, Fruits and Vegetables in Occurrence and Progression of Endometriosis."
	
Ning, F., et al. (2022). "A NON-CANONICAL ROLE FOR CCL2 IN T CELL MIGRATION: IMPROVING DUAL-INTERFERON-TREATED AUTOLOGOUS MONOCYTES AS A THERAPY FOR OVARIAN CANCER." Journal for Immunotherapy of Cancer 10(Supplement 2): A427.
	Background Ovarian cancer is the fifth leading cause of cancer- related death in women in the US and the most lethal gynecologic malignancy. Although many patients respond initially to platinum-based chemotherapy, over 70% of patients diagnosed with advanced stage ovarian cancer relapse within 24 months and have limited second-line treatment options. Our group pioneered an approach manipulating innate immunity where autologous monocytes, interferon-gamma, and interferon-alpha2b (AMIGA) were given intraperitoneally to women with recurrent, ovarian cancer in order to directly kill tumor cells and mitigate the immunosuppressive tumor microenvironment. Methods 18 patients were enrolled in the Phase 1 clinical trial (NCT02948426). Peripheral blood mononuclear cells (PBMCs) were collected from patients pre- and post-treatment cycles. Malignant ascites was collected when present. PBMCs were used for bulk and single-cell RNA-sequencing. Downstream analysis was completed on the NIH's Integrated Data Analysis Platform. LegendPlex Essential Immune Response kit (Biolegend #740930) was used to quantify ascites' cytokines. For migration assays, conditioned media from 2D and 3D ovarian cancer cell cultures treated with AMIGA was used to assess T cell migration. Migration was assayed 24 hours after T cells were exposed to conditioned media by flow cytometry or spinning disk confocal microscopy. Results Of the 18 enrolled patients, two had partial responses and four had stable disease. Of these, both responders and two of the four patients with stable disease maintained clinical benefit for five or more months, and were thus labelled as long-term responders (LTRs). Through bulk-cell RNA-sequencing, the PBMCs of these LTRs showed increased levels of T cell activation and migration genes compared to the 14 nonresponders (NRs). In light of this, we assessed patient malignant ascites for relevant chemokines and found CCL2, a known monocyte, and less so T cell, trafficking molecule, had increased in response to treatment. We then validated in vitro that CCL2 is significantly increased in the supernatants of AMIGA-treated ovarian cancer cells, but that this increase correlated with increased T cell, and not monocyte, migration. Furthermore, by manipulating the CCL2-CCR2 signaling axis in vitro, we were able to significantly alter T cell migration. Conclusions Overall, our findings suggest AMIGA aids T cell migration towards ovarian cancer by increasing the production of CCL2. By further understanding how AMIGA contributes to T cell migration and function in the ovarian cancer tumor microenvironment, we seek to combine innate- and adaptivebased immunotherapies to improve the treatment options and, ultimately, survival of women with ovarian cancer.

Ninivaggio, C. S., et al. (2021). "Perineorrhaphy Outcomes Related to Body Imagery: A Randomized Trial of Body Image Perception." Female Pelvic Medicine & Reconstructive Surgery 27(5): 281-288.
	OBJECTIVES: The aim of this study was to determine if a perineorrhaphy at the time of apical pelvic organ prolapse surgery positively affects women's body image. METHODS: This is a randomized controlled trial of women undergoing apical suspension procedures in which women (GH ≥2 cm to ≤6 cm) received either perineorrhaphy or no perineorrhaphy. The primary aim compared body image between the groups postoperatively using the Body Image in Pelvic Organ Prolapse (BIPOP) questionnaire. Secondary outcomes included prolapse stage, pain, pelvic floor muscle strength, pelvic floor symptoms, and sexual function. Between- and within-group differences were compared using Fisher exact test for categorical variables and t tests for continuous variables. When continuous variables were not normally distributed, the Welch-Satterthwaite test was used. Within-group analyses were performed via paired t tests for select continuous variables. RESULTS: Forty-six women were enrolled; 45 (97.8%) completed the 6-week assessment and 38 (82.6%) completed the 3-month assessment. There were no differences in baseline characteristics. Although women within groups had an expected improvement in mean Body Image in Pelvic Organ Prolapse and subscale scores between baseline and 3 months (P < 0.05), there were no differences in the mean scores between groups. In addition, there were no differences between groups in any of the secondary outcomes. CONCLUSIONS: Performance of apical prolapse surgery improved women's body image, irrespective of performance of a perineorrhaphy. Other important outcomes, including pain, did not differ between women in the 2 groups. These findings demonstrate the need for further trials to investigate the utility of this procedure.

Nipp, R. D., et al. (2022). "Effect of a Symptom Monitoring Intervention for Patients Hospitalized with Advanced Cancer: A Randomized Clinical Trial." JAMA Oncology 8(4): 571-578.
	Importance: Symptom monitoring interventions are increasingly becoming the standard of care in oncology, but studies assessing these interventions in the hospital setting are lacking. Objective(s): To evaluate the effect of a symptom monitoring intervention on symptom burden and health care use among hospitalized patients with advanced cancer. Design, Setting, and Participant(s): This nonblinded randomized clinical trial conducted from February 12, 2018, to October 30, 2019, assessed 321 hospitalized adult patients with advanced cancer and admitted to the inpatient oncology services of an academic hospital. Data obtained through November 13, 2020, were included in analyses, and all analyses assessed the intent-to-treat population. Intervention(s): Patients in both the intervention and usual care groups reported their symptoms using the Edmonton Symptom Assessment System (ESAS) and the 4-item Patient Health Questionnaire-4 (PHQ-4) daily via tablet computers. Patients assigned to the intervention had their symptom reports displayed during daily oncology rounds, with alerts for moderate, severe, or worsening symptoms. Patients assigned to usual care did not have their symptom reports displayed to their clinical teams. Main Outcomes and Measures: The primary outcome was the proportion of days with improved symptoms, and the secondary outcomes were hospital length of stay and readmission rates. Linear regression was used to evaluate differences in hospital length of stay. Competing-risk regression (with death treated as a competing event) was used to compare differences in time to first unplanned readmission within 30 days. Result(s): From February 12, 2018, to October 30, 2019, 390 patients (76.2% enrollment rate) were randomized. Study analyses to assess change in symptom burden included 321 of 390 patients (82.3%) who had 2 or more days of symptom reports completed (usual care, 161 of 193; intervention, 160 of 197). Participants had a mean (SD) age of 63.6 (12.8) years and were mostly male (180; 56.1%), self-reported as White (291; 90.7%), and married (230; 71.7%). The most common cancer type was gastrointestinal (118 patients; 36.8%), followed by lung (60 patients; 18.7%), genitourinary (39 patients; 12.1%), and breast (29 patients; 9.0%). No significant differences were detected between the intervention and usual care for the proportion of days with improved ESAS-physical (unstandardized coefficient [B] = -0.02; 95% CI, -0.10 to 0.05; P =.56), ESAS-total (B = -0.05; 95% CI, -0.12 to 0.02; P =.17), PHQ-4-depression (B = -0.02; 95% CI, -0.08 to 0.04; P =.55), and PHQ-4-anxiety (B = -0.04; 95% CI, -0.10 to 0.03; P =.29) symptoms. Intervention patients also did not differ significantly from patients receiving usual care for the secondary end points of hospital length of stay (7.59 vs 7.47 days; B = 0.13; 95% CI, -1.04 to 1.29; P =.83) and 30-day readmission rates (26.5% vs 33.8%; hazard ratio, 0.73; 95% CI, 0.48-1.09; P =.12). Conclusions and Relevance: This randomized clinical trial found that for hospitalized patients with advanced cancer, the assessed symptom monitoring intervention did not have a significant effect on patients' symptom burden or health care use. These findings do not support the routine integration of this type of symptom monitoring intervention for hospitalized patients with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03396510.Copyright © 2022 American Medical Association. All rights reserved.

Nirgianakis, K., et al. (2022). "Effectiveness of Dietary Interventions in the Treatment of Endometriosis: a Systematic Review." Reproductive sciences (Thousand Oaks, Calif.) 29(1): 26-42.
	A patients' increasing interest in dietary modifications as a possible complementary or alternative treatment of endometriosis is observed. Unfortunately, the therapeutic potential of dietary interventions is unclear and to date no guidelines to assist physicians on this topic exist. The aim of this study, therefore, was to systematically review the existing studies on the effect of dietary interventions on endometriosis. An electronic-based search was performed in MEDLINE and COCHRANE. We included human and animal studies that evaluated a dietary intervention on endometriosis-associated symptoms or other health outcomes. Studies were identified and coded using standard criteria, and the risk of bias was assessed with established tools relevant to the study design. We identified nine human and 12 animal studies. Out of the nine human studies, two were randomized controlled trials, two controlled studies, four uncontrolled before-after studies, and one qualitative study. All of them assessed a different dietary intervention, which could be classified in one of the following principle models: supplementation with selected dietary components, exclusion of selected dietary components, and complete diet modification. Most of the studies reported a positive effect on endometriosis; they were however characterized by moderate or high-risk bias possibly due to the challenges of conducting dietary intervention trials. According to the available level of evidence, we suggest an evidence-based clinical approach for physicians to use during consultations with their patients. Further well-designed randomized controlled trials are needed to accurately determine the short-term and long-term effectiveness and safety of different dietary interventions. (© 2020. The Author(s).)

Nisekhkhuu, A., et al. (2023). "To explore the effect of clomiphene citrate on the cycle characteristics and outcomes of women with polycystic ovarian syndrome." Journal of Obstetrics and Gynaecology Research 49(Supplement 1): 46-47.
	Aim: The aim of this study was to explore the effect of clomiphene citrate on the cycle characteristics and outcomes of women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation. Method(s): This is a cross sectional study, and it was conducted at the tertiary-care medical center. This study included 55 PCOS patients and 54 without PCOS patients undergoing ovarian mild stimulation. In the study group, CC and HMG were administered simultaneously beginning on cycle day 3,; while in control group without PCOS (n = 54) similar protocol treatment was used. Ovulation was co triggered by hCG when dominant follicles matured. The primary outcome measure was the HMG dose, number of dominant follicles and number of oocytes. Secondary outcomes included the number of quality embryos, fertilization rate, incidence of OHSS, pregnancy rate. Result(s): The study group received obviously lower total HMG dose 470.54 +/- 304.5 versus 500.00 +/- 287.59 IU, but similar HMG duration. While the antral follicle count is higher in study group, the number of oocytes retrieved and quality embryos.CC has a positive influence (higher oocytes retrieved and top quality embryos) on cycle characteristics, but might be correlated with the impaired IVF outcomes (lower E2,; lower implantation rate) in PCOS patients undergoing IVF, when CC + HMG used simultaneously. Conclusion(s): Mild stimulation resulted in increased levels of mature oocytes and biochemical and clinical pregnancies in study group compared with the controls. The results of the CC combined regimen provide a new insight into the development of a more patient-friendly protocol for women with PCOS.

Nisha, K. and R. Jha (2023). "Comparison of the Effects of Phytoestrogen and Conjugated Oestrogen on Vasomotor Symptoms in Surgical Menopause." International Journal of Pharmaceutical and Clinical Research 15(4): 1406-1411.
	Background: Menstruation ceasing permanently is referred to as menopause. Women go through a variety of physical, mental, and emotional changes throughout this trimester. Phytoestrogens, a class of chemicals generated from plants that bind to oestrogen receptors and have structural similarities to oestrogen, are used to treat vasomotor symptoms. The goal of the current study was to investigate how phytoestrogen and conjugated oestrogen affected vasomotor symptoms. The purpose of this study is to compare phytoestrogen and low dose conjugated oestrogen for the reduction of vasomotor symptoms in surgically menopausal women. Method(s): 128 surgically menopausal women who experienced vasomotor symptoms within six weeks of their recovery were divided evenly into two groups by chance. For 12 weeks, one group received conjugated oestrogen (Premarin) at a dose of 0.625 mg per day, whereas the other received soy isoflavone (70%) at a dose of 100 mg per day (lsoflav CR). Daily self-reports on the episode and intensity of vasomotor symptoms were taken. Up until the end of the 12-week period, evaluations were performed every four weeks. Result(s): The 12-week treatment cycle was completed by 52 women in the phytoestrogen group (n=52) and 58 women in the conjugated oestrogen group (n=58). After 12 weeks of treatment, 48 (82.75%) of the women (n=58) in the conjugated oestrogen group experienced considerably fewer hot flashes than the 14 (26.92%) of the women (n=52) in the phytooestrogen group. Only in the conjugated oestrogen group, 38 (65.51%) of the women (n=58) reported fewer night sweats. Both groups were deemed to be quite safe and well-accepted, with the exception of a few minor adverse effects in the conjugated oestrogen group such nausea, breast soreness, headache, etc. Conclusion(s): Contrary to phytooestrogen, conjugated oestrogen significantly decreased the severity and occurrence of vasomotor symptoms in surgical menopause, and both phytooestrogen and conjugated oestrogen were shown to be well tolerated and safe over the course of a 12-week research.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Nisha, K. and R. Jha (2023). "Comparison of the Effects of Phytoestrogen and Conjugated Oestrogen on Vasomotor Symptoms in Surgical Menopause."  15(4): 1406‐1411.
	Background: Menstruation ceasing permanently is referred to as menopause. Women go through a variety of physical, mental, and emotional changes throughout this trimester. Phytoestrogens, a class of chemicals generated from plants that bind to oestrogen receptors and have structural similarities to oestrogen, are used to treat vasomotor symptoms. The goal of the current study was to investigate how phytoestrogen and conjugated oestrogen affected vasomotor symptoms. The purpose of this study is to compare phytoestrogen and low dose conjugated oestrogen for the reduction of vasomotor symptoms in surgically menopausal women. Method: 128 surgically menopausal women who experienced vasomotor symptoms within six weeks of their recovery were divided evenly into two groups by chance. For 12 weeks, one group received conjugated oestrogen (Premarin) at a dose of 0.625 mg per day, whereas the other received soy isoflavone (70%) at a dose of 100 mg per day (lsoflav CR). Daily self‐reports on the episode and intensity of vasomotor symptoms were taken. Up until the end of the 12‐week period, evaluations were performed every four weeks. Results: The 12‐week treatment cycle was completed by 52 women in the phytoestrogen group (n=52) and 58 women in the conjugated oestrogen group (n=58). After 12 weeks of treatment, 48 (82.75%) of the women (n=58) in the conjugated oestrogen group experienced considerably fewer hot flashes than the 14 (26.92%) of the women (n=52) in the phytooestrogen group. Only in the conjugated oestrogen group, 38 (65.51%) of the women (n=58) reported fewer night sweats. Both groups were deemed to be quite safe and well‐accepted, with the exception of a few minor adverse effects in the conjugated oestrogen group such nausea, breast soreness, headache, etc. Conclusion: Contrary to phytooestrogen, conjugated oestrogen significantly decreased the severity and occurrence of vasomotor symptoms in surgical menopause, and both phytooestrogen and conjugated oestrogen were shown to be well tolerated and safe over the course of a 12‐week research.

Nishida, S., et al. (2022). "Cellular and Humoral Immune Responses Induced by an HLA Class I-restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer." Journal of immunotherapy (Hagerstown, Md. : 1997) 45(1): 56-66.
	The HLA-A*24:02-restricted peptide vaccine targeting Wilms' tumor 1 (WT1) (WT1 vaccine) is a promising therapeutic strategy for ovarian cancer; however, its efficacy varies among patients. In this study, we analyzed WT1-specific immune responses in patients with advanced or recurrent ovarian cancer that was refractory to standard chemotherapies and their associations with clinical outcomes. In 25 patients, the WT1 vaccine was administered subcutaneously weekly for 3 months and biweekly thereafter until disease progression or severe adverse events. We assessed Wilms' tumor 1-specific cytotoxic T lymphocytes (WT1-CTLs) and Wilms' tumor 1 peptide-specific immunoglobulin G (WT1235-IgG). After vaccination, the percentage of tetramer high-avidity population of WT1-CTLs among CD8+ T lymphocytes (%tet-hi WT1-CTL) and the WT1235-IgG titer increased significantly, although the values were extremely low or below the limit of detection before vaccination (%tet-hi WT1-CTL: 0.003%-0.103%.; WT1235-IgG: <0.05-0.077 U/mL). Patients who had %tet-hi WT1-CTL of ≥0.25% (n=6) or WT1235-IgG of ≥0.10 U/mL (n=12) had a significantly longer progression-free survival than those of patients in the other groups. In addition, an increase in WT1235-IgG corresponded to a significantly longer progression-free survival (P=0.0496). In patients with systemic inflammation, as evidenced by elevated C-reactive protein levels, the induction of tet-hi WT1-CTL or WT1235-IgG was insufficient. Decreased serum albumin levels, multiple tumor lesions, poor performance status, and excess ascites negatively influenced the clinical effectiveness of the WT1 vaccine. In conclusion, the WT1 vaccine induced antigen-specific cellular and humoral immunity in patients with refractory ovarian cancer. Both %tet-hi WT1-CTL and WT1235-IgG levels are prognostic markers for the WT1 vaccine. (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Nishikawa, T., et al. (2023). "Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2-Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(15): 2789-2799.
	Purpose: To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2.; Patients and Methods: Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety.; Results: The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively.; Conclusion: Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment.

Nishimura, A., et al. (2023). "Surgical efficacy and quality of wide resection of the pelvic peritoneum in patients with epithelial ovarian cancer." Surgical Oncology 48: 101946.
	Purpose: The aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed "wide resection of the pelvic peritoneum," (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum.; Methods: A total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining.; Results: With respect to patients with stage IIIA-IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17-0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors.; Conclusion: The present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA-IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.; Competing Interests: Declaration of competing interest The authors declare no conflict of interest with respect to the authorship and publication of this article. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nishina, T., et al. (2022). "Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 study." BMJ Open 12(10): e055718.
	Objectives We assessed the safety, tolerability, pharmacokinetics, preliminary antitumour activity and pharmacodynamics of danvatirsen, an antisense oligonucleotide targeting signal transducer and activator of transcription 3 (STAT3), monotherapy and danvatirsen plus durvalumab, an antiprogrammed cell death ligand 1 monoclonal antibody, in patients with advanced solid malignancies. Design Phase 1, open-label study with two cohorts. Setting Two centres in Japan. Participants Japanese individuals aged >=20 years, with histologically confirmed solid malignancies, except for hepatocellular carcinoma, refractory to standard therapy. Interventions In cohort 1, patients received danvatirsen monotherapy; in cohort 2, patients received danvatirsen plus durvalumab combination therapy. Primary and secondary outcome measures The primary endpoint was safety and tolerability based on adverse events (AEs). Secondary endpoints were pharmacokinetics, immunogenicity, antitumour activity and pharmacodynamics. Results Eleven patients were assigned to treatment and included in the analysis. Danvatirsen dose reductions were only required in cohort 2 for hepatic function abnormal (alanine aminotransferase (ALT)/ aspartate aminotransferase (AST)/gamma-glutamyl transferase (gammaGT) increased), neutrophil count decreased and platelet count decreased. One patient experienced grade 3 ALT/AST increased and new appearance of eosinophilia as a dose-limiting toxicity. AEs were reported in 90.9% (10/11) patients. Commonly reported AEs causally related to the danvatirsen were platelet count decreased (60% (3/5)) and ALT/AST/gammaGT increased (50% (3/6)) in cohorts 1 and 2, respectively; none was causally related to durvalumab. One serious AE occurred in cohort 1 (pancreatitis; unrelated to study treatment). One case of ALT/AST/gammaGT increased occurred in cohort 2, leading to discontinuation. No AEs led to death. Danvatirsen did not accumulate in plasma after multiple dosing. In cohort 2, three patients had disease control at 12 weeks and one had unconfirmed partial response. STAT3 expression tended to decrease regardless of monotherapy or combination therapy. Conclusions Danvatirsen was well tolerated by Japanese patients with advanced solid tumours as monotherapy and combined with durvalumab. No new safety signals arose. Trial registration number NCT03394144; ClinicalTrials.gov.Copyright ©

Nishio, S., et al. (2022). "Treatment specialty-specific characteristics and outcomes in women with vulvo-vaginal melanoma: A Japanese Gynecologic Oncology Group study (146)." Gynecologic Oncology 166(Supplement 1): S90.
	Objectives: To compare characteristics and outcomes of women with vulvovaginal melanoma based on treating physician types. Method(s): This is a multi-center retrospective study via the Japanese Gynecologic Oncology Group mechanism, examining 211 women with vulvovaginal melanoma (n=104 for vulva and n=107 for vagina). In each organ group, patient/tumor characteristics and survival outcomes were compared per the treating specialty type (gynecologist vs dermatologist). Propensity score inverse probability of treatment weighting was used to assess all-cause mortality. Result(s): In the vulvar melanoma group (n=67 per gynecologist's vs n=37 per dermatologists), patients treated by dermatologists were more likely to have stage III-IV disease (54.1% vs 28.4%, odds ratio [OR]: 3.19, 95% CI: 1.21-8.43, p=0.019) in multivariable analysis. In a weighted model, overall survival was similar between the dermatologist and gynecologist groups (5-year rate 40.5% vs 46.0%, HR: 1.39, 95% CI: 0.84-2.29, p=0.203). In the vaginal melanoma group (n=81 per gynecologists' vs n=26 per dermatologists), patients treated by dermatologists were more likely to be older (median, 74 vs 64 years, p=0.001) and had ulcerated tumors (84.6% vs 30.9%, OR: 18.1, 95% CI: 4.87-67.2, p<0.001) in multivariable analysis. In a weighted model, the dermatology group had improved overall survival compared to the gynecology group (5-year rate, 58.1% vs 26.8%, HR: 0.44, 95% CI: 0.26-0.75, p=0.003). Conclusion(s): This study suggests that women with vulvovaginal melanoma treated by dermatologists are distinct from those who are treated by gynecologists. Effects of multidisciplinary approach on treatment outcome warrant further evaluation.Copyright © 2022 Elsevier Inc.

Nishio, S., et al. (2022). "Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE-826." Cancer Science 113(11): 3877-3887.
	Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m 2 + cisplatin 50 mg/m 2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD-L1 combined positive score (CPS) ≥1, all-comers, and PD-L1 CPS ≥10. Fifty-seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD-L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16-0.77]), all-comers (n = 57; 0.45 [0.22-0.90]), and patients with PD-L1 CPS ≥10 (n = 25; 0.36 [0.12-1.07]). HRs (95% CI) for OS were 0.38 (0.14-1.01), 0.41 (0.17-1.00), and 0.37 (0.10-1.30), respectively. Incidence of grade 3-5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE-826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer. (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Nishio, S., et al. (2022). "Safety and efficacy of MORAb-202 in patients (pts) with platinum-resistant ovarian cancer (PROC): Results from the expansion part of a phase 1 trial." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: MORAb-202 is an antibody-drug conjugate consisting of farletuzumab (an antibody that binds to folate receptor alpha [FRalpha]) paired with eribulin mesylate (a microtubule dynamics inhibitor) conjugated via a cathepsin-B-cleavable linker. The dose-escalation part of this phase 1 study confirmed antitumor activity in pts with ovarian cancer (Shimizu 2021, CCR); based on efficacy and safety, MORAb-202 0.9 mg/kg and 1.2 mg/kg Q3W were chosen as doses for the expansion part of this study in pts with PROC. Method(s): The primary objective for the expansion part of this phase 1 study conducted in Japan was to define the safety and tolerability of MORAb-202. Secondary objectives included PK characterization and efficacy assessment (best overall response, objective response rate, progression-free survival, and overall survival). Eligible pts included those who had received <=2 regimens of chemotherapy after diagnosis of PROC, had measurable disease per RECIST v1.1, and an ECOG PS of <=1. Pts (except those with high grade serous histology) in the expansion phase were required to be FRalpha positive. The expansion phase began at the 0.9 mg/kg dose (Cohort 1); Cohort 2 (1.2 mg/kg) was initiated after safety assessment of Cohort 1 was completed. Tumor responses were assessed per RECIST v1.1 by investigator. Result(s): Twenty-four pts were treated in Cohort 1 and 21 pts were treated in Cohort 2. Grade >=3 TEAEs occurred in 33.3% of pts in Cohort 1 and 28.6% of pts in Cohort 2. The most common TEAE was interstitial lung disease (ILD)/pneumonitis at both dose levels (Cohort 1: 37.5% [n=9; 8 with grade 1, 1 with grade 2]; Cohort 2: 66.7% [n=14; 6 with grade 1, 7 with grade 2, 1 with grade 3]). Other common TEAEs of any grade were nausea (25.0%; 33.3%), pyrexia (33.3%; 42.9%), malaise (16.7%; 28.6%), and headache (12.5%; 47.6%), in Cohorts 1 and 2, respectively. ORR was 25.0% and 52.4% in Cohorts 1 and 2, respectively (Table). Antitumor activity was observed across FRalpha-expression levels (<50% and >=50%) and will be presented. Conclusion(s): In the PROC population, antitumor activity was seen with both the MORAb-202 0.9 mg/kg and 1.2 mg/ kg doses. While pt numbers were small, efficacy was observed irrespective of FRalpha-expression levels. ILD/pneumonitis was the most common TEAE and was low grade in most pts. Dose optimization is ongoing to maximize the benefit/risk profile of MORAb-202.

Nishio, S., et al. (2022). "SAFETY AND EFFICACY OF MORAB-202 IN PATIENTS WITH PLATINUM-RESISTANT OVARIAN CANCER: RESULTS FROM THE EXPANSION PART OF A PHASE 1 TRIAL IN JAPAN." International Journal of Gynecological Cancer 32(Supplement 2): A253-A254.
	Introduction/Background MORAb-202 is an antibody-drug conjugate consisting of farletuzumab (an antibody targeting folate-receptor alpha [FRalpha]) and eribulin mesylate (a microtubule dynamics inhibitor) conjugated via a cathepsin-B-cleavable linker. Antitumour activity was observed in the doseescalation part of this phase 1 study; MORAb-202 0.9 mg/kg and 1.2 mg/kg Q3W were chosen for the expansion part of this study in patients with platinum-resistant ovarian cancer (PROC). Methodology The primary objective for the expansion part of this phase 1 study was to define the safety and tolerability of MORAb-202. Secondary objectives included pharmacokinetic characterization and efficacy assessment (best overall response, ORR, PFS, and OS). Eligible patients had measurable disease per RECIST v1.1 and had <=2 chemotherapy regimens after PROC diagnosis. The expansion phase began at the 0.9 mg/kg dose (Cohort 1); Cohort 2 (1.2 mg/kg) was initiated after a Cohort 1 safety assessment. Tumour responses were assessed per RECIST v1.1 by investigator. Results Twenty-four patients were treated in Cohort 1; 21 patients were treated in Cohort 2. Grade >=3 TEAEs occurred in 33.3% of patients in Cohort 1; 28.6% of patients in Cohort 2. The most common TEAE was interstitial lung disease (ILD)/pneumonitis at both dose levels (Cohort 1: 37.5% [n=9; 8 with grade 1, 1 with grade 2]; Cohort 2: 66.7% [n=14; 6 with grade 1, 7 with grade 2, 1 with grade 3]). Other common TEAEs of any grade are in table 1. ORRs were 25.0% and 52.4% in Cohorts 1 and 2, respectively (table 1). Antitumour activity was observed across FRa-expression levels (<50% and >=50%) and will be presented. Conclusion In the PROC population, antitumour activity was seen with MORAb-202 0.9 mg/kg and 1.2 mg/kg dosages. Despite small patient numbers, efficacy was observed irrespective of FRa-expression levels. ILD/pneumonitis (mostly lowgrade) was the most common TEAE.

Nishioka, M., et al. (2023). "Pregnancy Rates after Hysteroscopic Endometrial Polypectomy versus Endometrial Curettage Polypectomy: A Retrospective Study." Medicina (Kaunas, Lithuania) 59(10).
	Background and Objectives : A relationship between endometrial polypectomy and in vitro fertilization (IVF) pregnancy outcomes has been reported; however, only a few studies have compared polyp removal techniques and pregnancy rates. We investigated whether different polypectomy techniques with endometrial curettage and hysteroscopic polypectomy for endometrial polyps affect subsequent pregnancy outcomes. Materials and Methods : Data from 434 patients who had undergone polypectomy for suspected endometrial polyps using transvaginal ultrasonography before embryo transfer in IVF at four institutions between January 2017 and December 2020 were retrospectively analyzed. Overall, there were 157 and 277 patients in the hysteroscopic (mean age: 35.0 years) and curettage (mean age: 37.3 years) groups, respectively. Single-blastocyst transfer cases were selected from both groups and age-matched to unify background factors. Results : In the single-blastocyst transfer cases, 148 (mean age: 35.0 years) and 196 (mean age: 35.9 years) were in the hysteroscopic and curettage groups, respectively, with the 148 cases matched by age. In these cases, the pregnancy rates for the first embryo transfer were 68.2% (odds ratio (OR): 2.14) and 51.4% (OR: 1.06) in the hysteroscopic and curettage groups, respectively; the resulting OR was 2.03. The pregnancy rates after up to the second transfer were 80.4% (OR: 4.10) and 68.2% (OR: 2.14) in the hysteroscopic and curettage groups, respectively, in which the OR was 1.91. The live birth rates were 66.2% (OR: 1.956) and 53.4% (OR: 1.15) in the hysteroscopic and curettage groups, respectively, in which the odds ratio was 1.71. These results show the effectiveness of hysteroscopic endometrial polypectomy compared to polypectomy with endometrial curettage. No significant difference was found regarding the miscarriage rates between the two groups. Conclusions : Hysteroscopic endometrial polypectomy resulted in a higher pregnancy rate in subsequent embryo transfer than polypectomy with endometrial curettage. Therefore, establishing a facility where polypectomy can be performed hysteroscopically is crucial.

Nitecki, R., et al. (2021). "Outcomes of the First Pregnancy After Fertility-Sparing Surgery for Early-Stage Cervical Cancer." Obstetrics and Gynecology 138(4): 565-573.
	OBJECTIVE: To evaluate outcomes of the first pregnancy after fertility-sparing surgery in patients with early-stage cervical cancer. METHODS: We performed a population-based study of women aged 18-45 years with a history of stage I cervical cancer reported to the 2000-2012 California Cancer Registry. Data were linked to the OSHPD (California Office of Statewide Health Planning and Development) birth and discharge data sets. We included patients with cervical cancer who conceived at least 3 months after a fertility-sparing surgery, which included cervical conization or loop electrosurgical excision procedure. Those undergoing trachelectomy were excluded. The primary outcome was preterm birth. Secondary outcomes included growth restriction, neonatal morbidity, stillbirth, cesarean delivery, and severe maternal morbidity. We used propensity scores to match similar women from two groups in a 1:2 ratio of case group participants to control group participants: population individuals without cancer and individuals with cervical cancer (women who delivered before their cervical cancer diagnosis). Wald statistics and logistic regressions were used to evaluate outcomes. RESULTS: Of 4,087 patients with cervical cancer, 118 (2.9%) conceived after fertility-sparing surgery, and 107 met inclusion criteria and were matched to control group participants. Squamous cell carcinoma was the most common histology (63.2%), followed by adenocarcinoma (30.8%). Patients in the case group had higher odds of preterm birth before 37 weeks of gestation compared with both control groups (21.5% vs 9.3%, odds ratio [OR] 2.7, 95% CI 1.4-5.1; 21.5% vs 12.7%, OR 1.9, 95% CI 1.0-3.6), but not preterm birth before 32 weeks. Neonatal morbidity was more common among the patients in the case group relative to those in the cervical cancer control group (15.9% vs 6.9%, OR 2.5, 95% CI 1.2-5.5). There were no differences in rates of growth restriction, stillbirth, cesarean delivery, and maternal morbidity. CONCLUSION: In a population-based cohort, patients who conceived after surgery for cervical cancer had higher odds of preterm delivery compared with control groups.

Nitta, Y., et al. (2022). "Secondary cancers after carbon-ion radiotherapy and photon beam radiotherapy for uterine cervical cancer: A comparative study." Cancer Medicine 11(12): 2445-2454.
	Background: There are limited studies on the risk of secondary cancers after carbon-ion radiotherapy (CIRT). We assessed the incidence of secondary cancers in patients treated with CIRT for cervical cancer. We also evaluated the incidence of secondary cancers in patients who received standard photon radiotherapy (RT) throughout the same period.; Methods: This retrospective study included patients with cervical cancer who underwent curative RT at our hospital. All cancers discovered for the first time after RT were classified as secondary cancers. To compare the risk of secondary cancers among cervical cancer survivors to the general population, standardized incidence ratios (SIRs) were calculated.; Results: The analysis included a total of 197 and 417 patients in the CIRT and photon RT groups, respectively. The total person-years during the observation period were 1052.4 in the CIRT group and 2481.5 in the photon RT group. The SIR for all secondary cancers was 1.1 (95% confidence interval [CI], 0.6-2.1) in the CIRT group and 1.4 (95% CI, 1.0-2.1) in the photon RT group. The 10-year cumulative incidence of all secondary cancers was 9.5% (95% CI, 4.0-21.5) in the CIRT group and 9.4% (95% CI, 6.2-14.1) in the photon RT group. The CIRT and photon RT groups were not significantly different in incidence (p = 0.268).; Conclusions: The incidence of secondary cancers after CIRT for cervical cancer was similar to that after photon RT. Validation of our findings after long-term observation is warranted. (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Niu, G., et al. (2023). "Single-Incision Plus One Port Laparoscopic Surgery for Myomectomy: A Retrospective Study." Journal of investigative surgery : the official journal of the Academy of Surgical Research 36(1): 2221738.
	Background: The purpose of this study was to evaluate the effect of single-incision plus one port laparoscopic surgery (SILS + 1) for myomectomy.; Methods: We retrospectively analyzed data from patients who underwent laparoendoscopic single-site myomectomy (LESS-M group, n = 40) and SILS + 1 (SILS + 1-M group, n = 40) for myomectomy at our hospital from October 2018 through December 2020. The patients' baseline demographic information and clinical data were compared between the two groups.; Results: The results showed that no significant difference in basic characteristics or between the number, size, and location of uterine myomas between the two groups ( p < 0.05). However, the surgery was more difficult and the total operating time was significantly longer in the LESS-M group compared to the SILS + 1-M group (83.5 ± 14.2 vs . 108.2 ± 18.1 min, p = 0.001). Moreover, the estimated intraoperative blood loss (113.4 ± 46.5 vs . 211.4 ± 60.3 ml, p = 0.001) and changes in hemoglobin level (13.1 ± 7.6 vs . 18.2 ± 6.0, p = 0.001) were significantly lower in the SILS + 1-M group compared to the LESS-M group. In addition, no serious intraoperative or postoperative complications occurred after surgery in either group. The clinical outcomes in the SILS + 1-M group were associated with a significant reduction in total surgical time compared to the LESS-M group ( p < 0.05).; Conclusion: SILS + 1 for myomectomy is popular in clinics, with a satisfactory clinical effect.

Niu, J. (2023). "9888 Effects of Early Second-Look Hysteroscopy Combined with Intrauterine Balloon Dilatation on Reproductive Outcomes for Women with IUAs." Journal of Minimally Invasive Gynecology 30(11 Supplement): S92.
	Study Objective: To develop a safe and effective treatment for preventing recurrence after hysteroscopic transcervical resection of adhesions (TCRA) of intrauterine adhesions (IUA). Design(s): Retrospective cohort study. Setting(s): Single hospital. Patients or Participants: 203 patients with IUA from April 2017 to December 2020. Intervention(s): As the study group, 109 patients underwent TCRA within 3-7 days after the end of menstruation (secondary amenorrhea was not altered by the menstrual cycle), the first hysteroscopic balloon dilatation was performed 10 days after the procedure, the second hysteroscopic exploration was performed 20 days after the procedure (or the second hysteroscopic exploration after the end of menstruation in case of menstruation), and so on for 2-3 cycles, and hysteroscopy was performed again 3 months after the procedure to assess the recovery of the uterine cavity; in the control group, 94 patients underwent hysteroscopy only at 3 months after the procedure to assess the recovery. All patients were routinely administered estrogen and aspirin postoperatively. Data from the two groups were analyzed and compared, including preoperative and postoperative American Fertility Society (AFS) scores, endometrial thickness in the early follicular phase, and menstrual volume, and patients were followed up for postoperative pregnancy outcomes. Measurements and Main Results: No intraoperative or postoperative complications such as uterine perforation, infection, fever, or abdominal pain were observed in both groups. The degree of postoperative uterine adhesions, menstrual status, and endometrial thickness showed significant improvement in both groups compared to the preoperative period (P > 0.05). However, the study group showed significant improvement in AFS score, menstrual volume and endometrial thickness compared with the control group. At follow-up, more patients in the study group had a successful pregnancy (48.5% vs. 30.8%, P<0.05). Conclusion(s): Early secondary hysteroscopic exploration combined with uterine balloon dilation after TCRA is safe and effective and improves the prognosis and postoperative pregnancy rate in patients with uterine adhesions.Copyright © 2023

Niu, X., et al. (2024). "Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with chemoradiotherapy for induction chemotherapy resistant locally advanced nasopharyngeal carcinoma: A prospective phase II study." Translational Oncology 39: 101797.
	Objectives: To investigate the efficacy and safety of nimotuzumab (NTZ) combined with concurrent chemo-radiotherapy (CCRT) in induction chemotherapy (IC) resistant locally advanced nasopharyngeal carcinoma (LANPC). Material(s) and Method(s): A single-arm, open-label phase II clinical trial was conducted (NCT04508816). Eligible patients were 18-70 years old, pathologically confirmed NPC at stage III-IVA, stable disease or progressive disease after IC by imaging evaluation, and ECOG performance status with 0-1. All patients received intensity-modulated radiotherapy (IMRT) concurrent with chemotherapy and NTZ (200 mg/w). The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. Result(s): From May 2015 to July 2020, 56 NPC patients were enrolled. With the median follow-up of 34 months (range from 8 to 77 months), the 3-year and 5-year PFS and OS rates were 79.3 % and 72.1 %, 94.0 % and 87.2 %, respectively. ORR of the nasopharynx and cervical lymph nodes involvement were 98.2 % and 98.1 % three months after IMRT. Univariate analysis revealed that pretreatment PET/CT was the factor that influenced PFS (P = 0.038). Patients treated with >=6 weeks of NTZ showed improved 3-year PFS rate (83.0% vs. 73.9 %, P > 0.05) and 5-year PFS rate (83.0% vs. 61.6 %, P>0.05) compared with <6 weeks NTZ. The acute toxicities were mainly grade 1/2 hematologic. Severe toxicities were uncommon. The major grade 3/4 AE was neutropenia (26.8 %). Conclusion(s): The results demonstrated that NTZ combined with CCRT in IC resistant LANPC was effective with mild toxicity.Copyright © 2023

Niu, Y., et al. (2022). "Ovulation induction regimens are associated with a higher rate of livebirth after frozen single-blastocyst transfer among women with polycystic ovary syndrome." Frontiers in Endocrinology 13: 987813.
	Background: Hormone replacement therapy (HRT) regimen was suggested to be associated with a decreased rate of livebirth and a higher risk of hypertensive disorders of pregnancy (HDP) after frozen cleavage stage embryo transfer in women with polycystic ovary syndrome (PCOS). With the dramatically increased use of elective single embryo transfer, there is great need to explore the impacts of different endometrial preparation regimens on frozen single-blastocyst transfer in women with PCOS.; Methods: In this study, a total of 3941 women who diagnosed with PCOS and underwent single-blastocyst transfer during their first cycles of frozen embryo transfer (FET) between March 2012 and December 2020 were included. We retrospectively compared the pregnancy and neonatal outcomes after frozen single-blastocyst transfer with endometrial preparation by HRT regimen (n = 3540), ovulation induction by human menopausal gonadotropin (hMG) regimen (n = 226), and ovulation induction by letrozole regimen (n = 175).; Results: After adjustment for confounders with multivariable logistic regression, the hMG regimen group [(58.4% vs. 49.6%; adjusted odds ratio (aOR): 1.43; 95% confidence interval (CI): 1.09-1.89)] and letrozole regimen group (58.9% vs. 49.6%; aOR: 1.42; 95% CI: 1.04-1.93) were associated with a higher rate of livebirth (primary outcome), compared with the group with HRT regimen. As to the secondary outcomes, the rate of pregnancy loss in the hMG regimen group (22.8% vs. 30.3%; aOR: 0.69; 95% CI: 0.48-1.00) and letrozole regimen group (16.9% vs. 30.3%; aOR: 0.48; 95% CI: 0.30-0.78) was also lower than that in the HRT regimen group. The pregnancy outcomes between the hMG regimen group and the letrozole regimen group were similar. We did not observe significant difference in the incidences of maternal and neonatal complications among these three groups.; Conclusion: Ovulation induction regimen with letrozole or hMG for endometrial preparation was associated with a higher livebirth rate and a lower pregnancy loss rate in frozen single-blastocyst transfer cycles among women with PCOS.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Niu, Zhao, Wang, Suo, Zou and Wei.)

Nivekkah, P., et al. (2022). "The effect of haemostatic sealants for ovarian cystectomy on ovarian reserve: A systematic review and meta-analysis."
	
Nl (2021). "Evaluation of endometrium stimulation with estrogen gestagen post hysteroscopic adhesiolysis and long term outcomes." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: exogenous hormone administration (oral administration of estrogen and gestagen) starting immediately after successful hysteroscopic adhesiolysis CONDITION: Asherman Syndrome PRIMARY OUTCOME: Spontaneous recurrence of intra uterine adhesion SECONDARY OUTCOME: ; • Ongoing pregnancy (in those patients willingly to conceive) after one year follow‐up. During a follow up of 1 year the number and time to conceive will be recorded. The clinical as well as the ongoing pregnancies (defined as intra‐uterine heart activity at 12 weeks gestation) ; ; • The number of performed re‐interventions (hysteroscopic adhesiolysis in the OR or outpatient clinic or adhesiolysis without hysteroscopy (dilatation) in outpatient clinic setting) ; ; • Complication related to postoperative estrogen and gestagen administration or any side‐effect. ; ; . Long term follow‐up over 10 years, re‐interventions, fertility outcome, pregnancy outcome, obstetrical outcome and chronicle pelvic pain INCLUSION CRITERIA: Consented patients with Asherman Syndrome (AS) who had a successful hysteroscopic adhesiolysis, defined as a restore of the normal uterine cavity, were eligible for inclusion. Patients with AS should be defined as patients with any diminishing of blood flow (secondary amenorrhoea or secondary hypomenorrhoe) after trauma to the uterine cavity due to pregnancy related surgical procedure with the presence of intrauterine adhesions with a previous history of normal menstrual blood flow.

Nl (2021). "Long-term follow up of overweight and obese women with PCOS who participated in a randomized controlled three-component lifestyle study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: N/A CONDITION: PCOS, overweight, obesity, lifestyle intervention, three‐component, cognitive behavioral therapy, diet, exercise. PRIMARY OUTCOME: The long‐term affect of a three‐component lifestyle intervention (with or without SMS support) on weight compared to care as usual. SECONDARY OUTCOME: The long‐term affect of a three‐component lifestyle intervention (with or without SMS support) on BMI, waist and hip circumference, emotional well‐being, PCOS characteristics, PCOS phenotype, and metabolic health compared to care as usual. INCLUSION CRITERIA: ‐ Previous participation in the ‘PCOS and overweight’ study. ‐ Informed consent.

Nl (2021). "SYMPRES study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intervention: Laparoscopic niche resection performed within 6 weeks after randomization. Control: Hormonal therapy (oral anticonceptives, progesterone, levenorgestrel IUD, GnRH agonist) for nine months. CONDITION: ‐ Niche ‐ Cesarean section scar defect ‐ Gynaecological symptoms ‐ Laparoscopy PRIMARY OUTCOME: Primary outcome is number of days of uterine blood loss between two menstruation, six months after randomisation, using avalidated blood loss calender to be filled in by the patient. SECONDARY OUTCOME: Secundary outcomes are gynaecological complaints such as heavy and/or painful uterine blood loss. Patient satisfaction andquality‐of‐life. Surgical outcomes, niche characteristics, re‐interventions, extra hormonal treatment or surgical interventions ninemonths after randomization. Medical consultations and costs INCLUSION CRITERIA: ‐ women 18 years or older ‐ pre‐menopausal (regular menstrual cyclus) ‐ large, symptomatic niche after caeserean section

Nl (2021). "VALUE study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: vNOTES hysterectomy CONDITION: Low grade endometrial cancer PRIMARY OUTCOME: percentage of patients treated in day‐care setting SECONDARY OUTCOME: Major complications, severity scored by Clavien‐Dindo classification; o injuries to bowel, bladder, ureter, vessels, nerves; o thrombo‐embolic events; o haematoma requiring surgical intervention; o haemorrhage requiring transfusion or surgical intervention; o wound dehiscence requiring surgical intervention; o wound infections including vaginal vault abscesses requiring surgical intervention or admission; Minor complications; o urinary tract infections in the first 2 weeks postoperative for which antibiotics are started; o surgical site infections; excluding vaginal vault abscesses that do not require surgical intervention but are treated expectantly ; or with antibiotics. ; Treatment related outcomes; o conversion rate (number of vNOTES cases that were converted to TLH) ; o operating time (measured from the start of the inscision until end of surgery); o time in operation room (measured from the entry and departure of the patients in the OR); o successful resection of adnexa; o total amount of CO2 used during procedure. (measured in litres CO2); o blood loss (measured in millilitres); o hospital stay (measured in hours); o usage of analgesics (usage and amount of paracetamol, NSAIDs or opioids); o resumption of daily activity (scored by return to daily activity questionnaire) ; o hospital readmission within 6 weeks after surgery ; o post‐operative pain the first 48 hours after surgery (measured on a numeric rating scale); Quality of life up to 12 weeks; o QoR‐40 questionnaire (day 1,2 and 7); o Recovery‐Index 10 (week 1,4,6, 12); INCLUSION CRITERIA: ‐ 18 years and older ‐ Written and orally given informed consent ‐ Patients with a histologically confirmed low grade endometrial carcinoma with no signs of progressive or metastatic disease ‐ Patients with atypical hyperplasia ‐ Clinical assessment of feasibility to perform laparoscopic or vNOTES hysterectomy with BSO

Nl (2021). "Virtual Reality ter pijnverlichting bij hysterosalpingografie." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Virtual Reality with the use of a ‘head mounted device’ (Sync VR Medical, Utrecht, The Netherlands) during the HSG. Participants will receive a demo of the VR device prior to the HSG and can choose between different relaxing and distracting modules. CONDITION: Infertility / tubal pathology PRIMARY OUTCOME: The primary endpoint is pain during the HSG. This measure consists of two components: the most severe pain (using a visual analogue scale 0‐10) and the overall pain (using a visual analogue scale 0‐10) SECONDARY OUTCOME: Secondary endpoints are: ; ‐ (Hypothetical) willingness to undergo another HSG if necessary; ‐ Use of oral analgesics during the first 24 hours after the HSG; ‐ ‘Immersiveness’ in the VR program; ‐ Side effects of the VR program ; INCLUSION CRITERIA: Women who: ‐ Will undergo an HSG with oil‐based contrast for infertility ‐ Have no history of cervical procedures ‐ Speak Dutch or English

Nocum, D. (2022). "Achieving significant radiation dose reductions for patients undergoing uterine artery embolisation - an Australian experience." Journal of Medical Radiation Sciences 69(SUPPL 1): 8.
	Introduction: From 2014 to 2020, Australian Medicare data showed only an average of 163 Medicare-funded uterine fibroid embolisation (UFE) procedures each year for the treatment of symptomatic fibroids. This was compared to an average of 30,757 uterine surgeries, where 13,126 were hysterectomies.1-3 There was an average of 6124 surgeries for fibroid disease per year, and an unknown number for adenomyosis.1,3 A united and stronger advocacy for UAE (uterine artery embolisation)/UFE procedures is needed in Australia, by increasing people's awareness of interventional procedures as alternatives to surgery, with minimal risks, lower cost and shorter recovery time.4 Methods: This study sought to demonstrate the low risks to ionising radiation when undergoing treatment with UAE/UFE procedures by achieving significant radiation dose reductions at our Australian centre using optimal interventional radiologist and interventional radiographer technique and an upgraded angiography system. Result(s): UAE practice on the previous system, Group I (Allura, n = 95), and the upgraded system, Group II (Azurion, n = 95) demonstrated a significant reduction in dose-area product and air kerma by (143.2 Gy cm2 vs 52.9 Gy cm2; P < 0.001, d = 0.8) and 67% (0.6 Gy vs 0.2 Gy; P < 0.001, d = 0.8), respectively. Conclusion(s): This study validated the upgraded system and its advanced capabilities and showed that interventional radiologist and interventional radiographer expertise are critical for dose optimisation at all centres performing UAE/UFE procedures. This Australian experience forms a united front to make this interventional procedure more appealing to people suffering from symptomatic benign uterine conditions.

Nocum, D. (2022). "Continuous quality improvement for uterine artery embolisation procedures reduces patient radiation dose while maintaining image quality." Journal of Medical Radiation Sciences 69(SUPPL 1): 8.
	Objectives: Uterine artery embolisation (UAE) is an effective treatment for patients with symptomatic uterine fibroids and/or adenomyosis and has united people across the land suffering from these benign conditions to seek alternatives to surgery.1,2 Our interventional radiology department performs the highest number of UAE procedures in Australia and has successfully treated patients with this minimally-invasive, interventional procedure.3 The purpose of this study was to introduce a continuous quality improvement (CQI) program and assess its impact on radiation dose reduction as well as image quality with the use of visual grading characteristics (VGC) analysis. Method(s): The interventional radiographer and interventional radiologist developed a CQI program to investigate the effects of optimising radiation dose parameters on the dose-area product and overall image quality by comparing a CQI intervention group (n = 50) and control group (n = 50). Result(s): A significant reduction in dose-area product by 17% (P = 0.041, d = 0.2) and air kerma by 20% (P = 0.027, d = 0.2) was shown between the two groups. The VGC analysis resulted in an area under the VGC curve (AUC-VGC) of 0.54 when using the control group as a reference, indicating no significant difference in image quality between the two groups (P = 0.670). Discussion/Conclusion: The implementation of the CQI program and optimisation of radiation dose parameters improved and unified the UAE radiation dose practices at our centre. The dose reduction demonstrated no detrimental effects on image quality.

Noé, G. K., et al. (2021). "Prospective International Multicenter Pelvic Floor Study: Short-Term Follow-Up and Clinical Findings for Combined Pectopexy and Native Tissue Repair." Journal of Clinical Medicine 10(2).
	UNLABELLED: Efforts to use traditional native tissue strategies and reduce the use of meshes have been made in several countries. Combining native tissue repair with sufficient mesh applied apical repair might provide a means of effective treatment. The study group did perform and publish a randomized trial focusing on the combination of traditional native tissue repair with pectopexy or sacrocolpopexy and observed no severe or hitherto unknown risks for patients (Noé G.K. J Endourol 2015;29(2):210-5.). The short-term follow-up of this international multicenter study carried out now is presented in this article. MATERIAL AND METHODS: Eleven clinics and 13 surgeons in four European counties participated in the trial. In order to ensure a standardized approach and obtain comparable data, all surgeons were obliged to follow a standardized approach for pectopexy, focusing on the area of fixation and the use of a prefabricated mesh (PVDF PRP 3 × 15 Dynamesh). The mesh was solely used for apical repair. All other clinically relevant defects were treated with native tissue repair. Colposuspension or TVT were used for the treatment of incontinence. Data were collected independently for 14 months on a secured server; 501 surgeries were registered and evaluated. Two hundred and sixty-four patients out of 479 (55.1%) returned for the physical examination and interview after 12-18 months. MAIN OUTCOME AND RESULTS: The mean duration of follow-up was 15 months. The overall success of apical repair was rated positively by 96.9%, and the satisfaction score was rated positively by 95.5%. A positive general recommendation was expressed by 95.1% of patients. Pelvic pressure was reduced in 95.2%, pain in 98.0%, and urgency in 86.0% of patients. No major complications, mesh exposure, or mesh complication occurred during the follow-up period. CONCLUSION: In clinical routine, pectopexy and concomitant surgery, mainly using native tissue approaches, resulted in high satisfaction rates and favorable clinical findings. The procedure may also be recommended for use by general urogynecological practitioners with experience in laparoscopy.

Noé Günter, K., et al. (2022). "Laparoscopic versus vaginal native tissue repair in combination with pectopexy. Sub-analysis from an international, prospective, and multi-centre study: short term results." Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 31(5): 782-788.
	Introduction: The use of mesh for vaginal repairs is currently problematic and as a consequence, there is increased interest in native tissue repair. We describe the follow-up data of a sub-analysis of a prospective and multi-center study focusing on the combination of pectopexy and native tissue repair. Patients were followed up for 12-18 months after surgery (+ SD: 15). Two-hundred and sixty-four patients attended the clinics for physical examination and were integrated into the follow-up. Cystocele repair was performed laparoscopically in 84 patients and vaginally in 52 patients. Posterior repair was performed vaginally in 40 patients and laparoscopically in 53 patients.; Results: Clinical success rate, patient recommendations and patient satisfaction rates were similar in both groups. The laparoscopic anterior repair resulted in an 89% cure or anatomical improvement rate; this compared to 94.2% for the vaginal approach. In the posterior group, laparoscopy resulted in a 94.3% cure or improvement rate compared to 97.5% in the second group.; Conclusions: The outcomes of both strategies showed satisfactory results in our study. Consequently, surgeons may choose between the two strategies according to their preference and skill. The two approaches only differed with regard to vaginal scarring. We suggest future research investigating the long-term impact of scarring.

Nogami, Y., et al. (2022). "Impact of COVID-19 on gynecologic cancer treatment in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO)." Journal of Gynecologic Oncology 33(1): e8.
	Objective: As coronavirus disease 2019 (COVID-19) rages on, it is a challenging task to balance resources for treatment of COVID-19 and malignancy-based treatment. For the development of optimal strategies, assessing the conditions and constrains in treatment during the COVID-19 pandemic is pertinent. This study reported about a nationwide survey conducted by the Japan Society of Gynecologic Oncology. Method(s): We interviewed 265 designated training facilities about the state of their clinical practice from the time period between March and December 2020. We asked the facility doctors in charge to fill a web-based questionnaire. Result(s): A total of 232 facilities (87.5%) responded. A decrease in the number of outpatient visits was reported, and the major reason attributed was reluctance of patients to visit hospitals rather than facility restrictions. The actual number of surgeries decreased by 3.9%, compared to 2019. There was a significant difference when the variable of "Prefectures operating under special safety precautions" or not was introduced. There was no increase in the rate of advanced stages in the three cancer types studied. However, 34.1% participants perceived COVID-19 affected management and prognosis. Conclusion(s): Refraining from visiting hospitals based on the patient's judgment may be expected to be an issue in the future. No significant decrease in surgeries was observed, and it would seem that there were few forced changes in treatment plans, but "the State of Emergency" had an impact. There was no increase in the rate of advanced cancers, but this will need to be monitored.Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Nogueira-Costa, G., et al. (2022). "Non-endometrioid endometrial cancer: Analysis of different adjuvant treatment modalities." Cancer treatment and research communications 32: 100581.
	Background: Adjuvant treatment for endometrial carcinoma (EC) is decided based on risk assessment. Tumors of non-endometrioid (NE) histology are classified as high-risk and adjuvant treatment is recommended.; Materials and Methods: We analyzed retrospectively all NEEC patients treated in two Portuguese oncology centers, between 2009 and 2018. Comparison of adjuvant modalities were performed by overall survival (OS) and disease-free survival (DFS) analysis.; Results: A total of 66 patients were included, with mean age 69 years. Serous histology was found in 34 patients (51.5%), clear-cell in 13 (19.7%) and carcinosarcoma in 18 (27.3%). Based on FIGO staging-system, 34 (51.5%) patients were diagnosed at stages III-IV. Following surgery, no further treatment was performed in 16 patients (24.4%), 11 (16.7%) received isolated chemotherapy (CT), 11 (16.7%) isolated radiotherapy (RT) and 28 (42.4%) combination therapy (CT+RT). Kaplan-Meier analysis showed higher median (m)DFS in the CT+RT group: 30.7 months (m) compared to RT alone: 14.1 m. The mDFS of the isolated CT group was 10.8 m and for patients with no further treatment it was 5.7 m, p = 0.03. Median OS was also increased in the combination group CT+RT (78.3 m) compared to isolated RT (64.3 m), isolated CT (37.3 m) and no further treatment (46.7 m), p=0.005. Multivariate Cox-regression using CT+RT as reference, showed hazard-ratio of 3.5 (p = 0.05) and 4.5 (p = 0.01) for the CT and for no-treatment group respectively.; Conclusions: In NEEC patients, DFS and OS analysis showed better prognosis in combination of CT+RT. Patients that underwent only RT had better survival outcomes when compared to those treated with CT only. (Copyright © 2022. Published by Elsevier Ltd.)

Noh Kyoung, W., et al. (2022). "Effect of Waiting Time from Pathological Diagnosis to Definitive Concurrent Chemoradiation for Cervical Cancer on Overall Survival." Cancer research and treatment 54(1): 245-252.
	Purpose: This study aimed to evaluate the effect of waiting time, from diagnosis to initiation of definitive concurrent chemoradiation (CCRT), on overall survival in cervical cancer patients.; Materials and Methods: Patients with cervical cancer who were treated with definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from initial pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in two groups (group 1 ≤ median, group 2 > median). Patients with a waiting time of more than 60 days were excluded.; Results: The median waiting time was 14 days (0-60). There were differences between group 1 and group 2 in age and chemotherapy regimens. However, no significant difference was found in the International Federation of Gynecology and Obstetrics stage, cell type, or the number of cycles of chemotherapy received during CCRT. A longer waiting time was associated with poorer overall survival on the Kaplan-Meier curve (group 1 vs. group 2, p=0.042). On multivariate analysis, intervals as either a continuous variable (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006 to 1.040; p=0.007) or a categorical variable (HR, 1.513; 95% CI, 1.073 to 2.134; p=0.018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival.; Conclusion: A shorter waiting time from pathological diagnosis to definitive CCRT showed benefit on overall survival. Our findings suggest that an effort to minimize waiting times should be recommended in cervical cancer patients who are candidates for CCRT.

Noh, Y., et al. (2021). "Discontinuation and Re-initiation of Antidepressants During Pregnancy: A Nationwide Cohort Study." Journal of Affective Disorders.
	BACKGROUND: Women tend to discontinue antidepressants during pregnancy. We examined the rate of and factors associated with antidepressant discontinuation and re-initiation during pregnancy. METHODS: We conducted a nationwide cohort study using Korea's healthcare database. The study cohort included women who were aged 15-50 years, gave birth during 2013-2017, had ≥1 depression diagnosis, ≥2 antidepressant prescriptions within 6 months (one within one month of preconception). Cox proportional hazards model was used to evaluate factors associated with antidepressant discontinuation and re-initiation during pregnancy. RESULTS: Among 5,207 pregnancies, 4,954 (95.1%) discontinued antidepressants during pregnancy, which included 4,657 (89.4%) in the first trimester, 1,810 (38.9%) of whom re-initiated them during pregnancy or postpartum period. The risk of antidepressant discontinuation increased in women with substance-related disorders (HR 1.17, 95% CI 1.01-1.35), but decreased in women receiving medical aid (0.53, 0.46-0.62) and patients suggestive of severe depression, such as psychiatric comorbidities and long-term antidepressant use before pregnancy. Antidepressant re-initiation occurred frequently in medical aid recipients (1.25, 1.06-1.47), nulliparous women (1.11, 1.01-1.22), and women with severe symptoms. CONCLUSIONS: We found high rates of antidepressant discontinuation and re-initiation during pregnancy. Although women suggestive of severe symptoms were less likely to discontinue antidepressants during pregnancy, they were more likely to re-initiate them during their perinatal period, which warrants more detailed guidelines on perinatal depression.

Nohri, A. R. and L. Lafont (2024). "EVALUATING THE EFFICACY OF WILD YAM HORMONAL SALVE IN MANAGING MENOPAUSAL SYMPTOMS: A COHORT STUDY." Journal of Population Therapeutics and Clinical Pharmacology 31(1): 382-391.
	Background: Menopause is a natural process characterized by a reduction in certain gonadal hormones in females in their 40s. A lot of changes can be seen as the symptoms of menopause, such as those related to the central nervous system, metabolic changes, and weight gain, changes in cardiovascular health, urogenital and skin problems, and sexual dysfunction. Transdermal mode of delivery provides a practical and less risky alternative to oral consumption of drugs and also aims to serve as a better alternative to hypodermic injection. Topical Wild yam releases diosgenin, a precursor of gonadal hormone for managing menopausal symptoms and balancing hormones. Method(s): A cohort study was done on females of age 40-49 years, who were experiencing menopausal symptoms. The observation of a group of 34 females was done over time of 21 days (three weeks-three follow-ups) on Dr Skin BEAUTYTM Wild Yam Hormonal Salve followed by placebo effect (14 days) to assess the impact of intervention. A purposive non-probability sampling technique was used to collect the data on designed questionnaire, to test the effectiveness of a natural balm, Dr Skin BEAUTYTM Wild Yam Hormonal Salve. An informed consent was taken from every participant before intervention. Result(s): Throughout the three subsequent evaluations, there was a persistent pattern of escalating beneficial outcomes observed with extended utilization of the hormonal salve, Dr Skin BEAUTYTM Wild Yam Hormonal Salve. Most individuals did not encounter any adverse effects, which reinforces the salve's safety profile. The occurrence of night sweats showed a consistent improvement, reaching a relief rate of 82.3% after duration of three weeks. At the start, vaginal dryness was a common problem for 85.2% of participants. However, after 21 days, there was a significant improvement, with 73.5% of participants reporting alleviation. The study consistently showed a good trend in both sleep disturbances and mood disturbances, with a sustained improvement of 76.5% recorded at the final follow-up. The decrease in sexual desire elicited diverse reactions, with a significant rise in the number of individuals (47.1%) expressing positive changes after a period of 21 days. Considerable alleviation of symptoms such as hot flashes, and joint/muscle discomfort was seen, underscoring the importance of ongoing monitoring. Significantly, the issue of weight increase, which was a concern for 11.8% of participants at the beginning, showed no change till last follow-up with the salve. Conclusion(s): The study explores the potential effectiveness of Dr Skin BEAUTYTM Wild Yam Hormonal Salve in reducing various postmenopausal symptoms over three weeks of treatment. Nonetheless, the variability in individual reactions underscores the complex nature of symptom management, emphasizing the need for personalized solutions and emphasizing the need for future research to gather a more precise understanding and establish customized treatment plans.Copyright © 2024, Codon Publications. All rights reserved.

Noiret, B., et al. (2022). "Update of randomized controlled trials evaluating cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in prevention and therapy of peritoneal metastasis: a systematic review." Pleura and Peritoneum 7(2): 51-61.
	Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with favorable short- and long-term oncological outcomes in highly selected patients with peritoneal metastasis (PM). The aim of our review was to review published, recruiting or ongoing randomized controlled trials (RCTs) evaluating CRS and HIPEC vs. other strategies (systemic chemotherapy or CRS alone) and to update the studies recently described in 2016.; Content: Systematic review according to PRISMA guidelines. Searches for published and ongoing trials were based, respectively, on PubMed and international clinical databases since 2016.; Summary: 46 trials randomized 9,063 patients: 13 in colorectal cancer (3 in therapeutic strategy and 10 in prophylactic strategy), 16 in gastric cancer (4 in therapeutic strategy and 12 in prophylactic strategy) and 17 in ovarian cancer (12 in front-line therapy and 5 in recurrence settings).; Outlook: In contrast to many recruiting studies, few published studies analyzed the potential advantage of CRS and HIPEC in therapeutic and prophylactic treatment of PM. The potential effect of this combined treatment has been proven in ovarian cancer in interval surgery, but remains still debated in other situations. Promising trials are currently recruiting to provide further evidence of the effectiveness of CRS and HIPEC.; Competing Interests: Competing interests: Authors state no conflict of interest. (© 2022 Barbara Noiret et al., published by De Gruyter, Berlin/Boston.)

Nokhostin, F. and M. Azadehrah (2020). "The Role of Neoadjuvant Chemotherapy in Non-SCC of the Cervix: A Systematic Review." European Journal of Molecular and Clinical Medicine 7(10): 2761-2776.
	Cervical cancer is the third most common cancer in women and the most significant cause of CC is HPV infection. One of the treatment methods for cervical cancer is pre-surgery neoadjuvant chemotherapy (NACT), which is performed to reduce the size of the tumor, facilitate the surgical process, and improve the survival of patients with this cancer. The present study is a systematic review conducted by searching the databases of Elsevier, PubMed Springer, and Wiley, and with the keywords of Cervix cancer, Adenocarcinoma, Adenosquamous carcinoma, and Neoadjuvant chemotherapy; studies conducted between 1998-2020 were reviewed. Out of a total of 1018 articles, 15 articles were selected for further review, considering the inclusion/exclusion criteria. The results showed that the use of NACT improved the patient's physical condition, reduced tumor size, reduced metastasis, facilitated surgery, and improved survival; also, it was associated with successful delivery without side effects in infants. However, further studies are needed to further understand the effect of this treatment in non-scc cancers.Copyright © 2020 Ubiquity Press. All rights reserved.

Noll, F., et al. (2021). "Neoadjuvant chemotherapy in early-stage cervical cancer (<2 cm) before conization for fertility preservation: is there any advantage over upfront conization?" International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(3): 379-386.
	Background: Neoadjuvant chemotherapy before fertility-sparing surgery is an accepted option for patients with cervical tumors between 2 cm and 4 cm. There is a paucity of data regarding its role in patients with tumors <2 cm. Our objective was to compare the oncological and obstetrical outcomes between patients who underwent neoadjuvant chemotherapy before cervical conization versus upfront cervical conization in patients with cervical cancer with tumors <2 cm.; Methods: We conducted a systematic literature review and searched MEDLINE, EMBASE, and CINAHL (from 1995 to March 2020) using the terms: uterine cervix neoplasms, cervical cancer, fertility-sparing surgery, fertility preservation, conization, cone biopsy, and neoadjuvant chemotherapy. We included manuscripts with information on patients with tumor size <2 cm, lymph node status, follow-up, oncological and obstetrical outcome, and toxicity related to neoadjuvant chemotherapy. We excluded review articles or articles with duplicated patient information.; Results: We identified 12 articles, including 579 patients. For final analysis, 261 patients met inclusion criteria. The most common histology was non-squamous cell carcinoma (62%). Median follow-up time was 63.5 (range 7-122) months for the neoadjuvant chemotherapy group and 48 (range 12-184) months for the upfront cervical conization group. There was no difference in either overall survival (neoadjuvant chemotherapy group 100% vs upfront cervical conization 99.7%, p=0.79) or disease-free survival (neoadjuvant chemotherapy 100% vs upfront cervical conization 98.9%, p=0.59) between the groups. Fertility preservation rate was 81.4% versus 99.1% (p<0.001) favoring upfront cervical conization. No statistically significant differences were seen in live birth rate or pregnancy loss. Also, we found that all neoadjuvant chemotherapy patients reported chemotherapy-related toxicity (30.7% grade 3 and 69.2% grade 1-2).; Conclusions: There was no difference in disease-free survival or overall survival between patients who underwent neoadjuvant chemotherapy followed by conization and upfront cervical conization. Patients who underwent upfront cervical conization had a higher fertility preservation rate.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Nonomura, Y., et al. (2022). "Ovarian Endometrioid and Clear Cell Carcinomas with Low Prevalence of Microsatellite Instability: A Unique Subset of Ovarian Carcinomas Could Benefit from Combination Therapy with Immune Checkpoint Inhibitors and Other Anticancer Agents." Healthcare (Basel, Switzerland) 10(4).
	Ovarian cancer has the highest mortality rate among all gynecological malignancies; therefore, a novel treatment strategy is needed urgently. Utilizing immune checkpoint inhibitors has been considered for microsatellite instability (MSI)-high (MSI-H) tumors. However, the prevalence of MSI-H tumors in ovarian endometrioid and clear cell carcinomas remains unclear. Here, polymerase chain reaction was used to analyze 91 cases of ovarian endometrioid and clear cell carcinomas for the MSI status and the relationship between MSI-H, immune checkpoint molecules, and clinicopathological factors (including patient survival). Only 5 of 91 (5%) cases were MSI-H endometrioid carcinomas. In these cases, CD-8 expression was significantly higher ( p = 0.026), confirming an enhanced immune response. From the survival curve, no statistical correlations were found between the MSI-H group and the microsatellite stable (MSS) group; however, the MSS group trended towards better progression-free survival than the MSI-H group ( p = 0.056). Patients with PD-L1 expression had shorter overall survival than those without ( p = 0.022). Thus, MSI-H is a rare event and not a favorable prognostic factor in ovarian endometrioid and clear cell carcinomas. Thus, to improve the prognosis of ovarian endometrioid carcinoma and clear cell carcinomas, a combination therapy of immune checkpoint inhibitors and other molecular targeted therapies may be required.

Nooij, L., et al. (2022). "Neoadjuvant chemotherapy for patients with locally advanced vulvar cancer." Current Opinion in Oncology 34(5): 466-472.
	Purpose of Review: Studies on treatment options for patients with locally advanced vulvar cancer (LAVC) are scarce, and high-level evidence for a primary treatment choice is lacking. Furthermore, current treatment options are associated with extensive morbidity and high complication rates. More effective treatment options are urgently needed. This review describes current treatment possibilities, focusing on literature regarding neoadjuvant chemotherapy (NACT) followed by surgery.; Recent Findings: Although data are heterogeneous and limited, NACT followed by surgery might be an effective and well tolerated treatment alternative associated with lower morbidity compared with current treatment options, such as excenterative surgery or definitive chemoradiation.; Summary: Up until now, several studies describe an overall response rate of 40-86%. Surgery turned out to be possible in 40-90% of the LAVC patients who received NACT. Prospective studies on the efficacy and safety of NACT followed by surgery with a homogeneous chemotherapy regimen are urgently awaited. NACT should, at this point, still be considered investigational. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Noor, N., et al. (2022). "Comparing Minimally Invasive Sacrocolpopexy With Vaginal Uterosacral Ligament Suspension: A Multicenter Retrospective Cohort Study Through the Fellows' Pelvic Research Network." Urogynecology (Philadelphia, Pa.) 28(10): 687-694.
	Importance: Comparing one-year surgical outcomes of two widely used surgical procedures for apical suspension.; Objectives: The objective of this study is to compare anatomic outcomes after minimally invasive sacrocolpopexy (MISC) and vaginal uterosacral ligament suspension (vUSLS).; Study Design: This was a multicenter, retrospective cohort study through the Fellows' Pelvic Research Network. Patients with ≥ stage II pelvic organ prolapse (POP) who underwent MISC or vUSLS from January 2013 to January 2016, identified through the Current Procedural Terminology codes, with 1 year or longer postoperative data were included. Patients with prior POP surgery or history of connective tissue disorders were excluded. Anatomic success was defined as Pelvic Organ Prolapse Quantification System measurements: Ba/Bp ≤ 0 or C ≤ -TVL/2. Data were compared using χ 2 or Fisher exact tests. Continuous data were compared using Wilcoxon rank sum test.; Results: Three hundred thirty-seven patients underwent MISC (171 laparoscopic, 166 robotic) and 165 underwent vUSLS. The MISC group had longer operative time (205.9 minutes vs 187.5 minutes, P = 0.006) and lower blood loss (77.8 mL vs 187.4 mL; P < 0.001). Two patients (0.6%) in the MISC group had mesh exposure requiring surgical excision. Permanent suture exposure was higher after vUSLS (6.1%). At 1 year, anatomic success was comparable in the apical (322 [97%] MISC vs 160 [97%] vUSLS, P = 0.99) and posterior compartments (326 [97.6%] MISC vs 164 [99.4%] vUSLS; P = 0.28). Anterior compartment success was higher in the MISC group (328 [97.9%] vs 156 [94.9%], P = 0.04) along with longer total vaginal length (9.2 ± 1.8 vs 8.4 ± 1.5, P < 0.001).; Conclusion: At 1 year, patients who underwent MISC or vUSLS had similar apical support. Low rates of mesh and suture exposures, less anterior recurrence, and longer TVL were noted after MISC.; Competing Interests: The authors have declared they have no conflicts of interest. (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Noori, N., et al. (2022). "The effect of endometrial scratching on reproductive outcomes in infertile women undergoing IVF treatment cycles." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(8): 3611-3615.
	This study was a Randomised Controlled Trial aiming to evaluate the effect of Endometrial Scratching (ES) on fertility rate. Participants were primary infertile women undergoing IVF treatment. ES for the intervention group was done using endometrial aspiration in the luteal phase of the cycle before embryo transfer. In both groups, 2-3 8-celled embryos were transferred after endometrial preparation by Oestrogen and Progesterone. There were no significant differences between the two groups in terms of age, BMI and endometrial thickness (ET). No significant differences were found between intervention and control groups in chemical pregnancy rate ( p = 0.410), clinical pregnancy ( p = 0.822), the number of abortions ( p = 0.282) and the implantation rate ( p = 0.777). Local ES had no significant effects in improving the IVF success rate and reducing the embryo abortion rate.Impact statement What is already known on this subject? Endometrial scratching (ES) is a local injury to the endometrium that was assumed to affect implantation in IVF and IUI cycles positively. However, various studies have shown conflicting results on this matter. What do the results of this study add? Local ES had no significant effects on improving the IVF success rate and reducing the embryo abortion rate in patients with the first IVF cycle. What are the implications of these findings for clinical practice and/or further research? Larger clinical trials can measure the usefulness of ES with higher powers. However, this study, along with other clinical trials, can help evaluate the ES effect in future meta-analyses.

Noorian, F., et al. (2023). "Are 7.5 Gyx2 fractions more efficient than 6 Gyx3 in exclusive postoperative endometrial cancer brachytherapy? A clinical and dosimetrical analysis." Radiotherapy and Oncology 189: 109909.
	Purpose: To compare two vaginal brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) patients considering vaginal-cuff relapses (VCR), late toxicities, dosimetry analysis and vaginal dilator use. Material(s) and Method(s): 110 PEC patients were treated with exclusive high-dose-rate VBT using two schedules. Group-1:44-patients received 6 Gyx3fractions (September-2011-April-2014); Group-2:66-patients were treated with 7.5 Gyx2fractions with a dose limit of equivalent total doses in 2-Gy fr (EQD2(alpha/beta=3)) of 68 Gy in the most exposed 2 cm3 of clinical target volume (CTV) (July-2015-November-2021). The dose was prescribed at 5 mm from the applicator surface. Were evaluated the overall radiation dose delivered to 90% of the CTV (D90), the CTV receiving 100% of the prescription dose (V100) and the EQD2(alpha/beta=3) received in the most exposed 2 cm3 to dose in CTV. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum and objective LENT-SOMA criteria for late vaginal toxicity (LVT). Statistics: Descriptive analysis, Chi-square, Student's t-tests and Kaplan and Meier method. Result(s): The median follow-up was 60 months (15.9-60). There were no VCR or late toxicities in bladder or rectum. LVT >= G1 appeared in 26/44 (59.1%) in Group-1 and 25/66 (37.9%) in Group-2. The mean EQD2(alpha/beta=3) received by the most exposed 2 cm3 of CTV was 63.7 Gy +/- 10.0 in Group-1 and 60.5 Gy +/- 3.8 in Group-2 (p = 0.063). There were no differences in adherence to vaginal dilator use >=9 months, overall D90 and V100. Conclusion(s): Considering the lack of vaginal relapses and similar LVT over time, 7.5 Gyx2fractions seem more efficient in terms of patient comfort, workload, and cost. This is the first study using dosimetry parameters to compare effectivity of schedules. Larger series are needed to confirm the present results.Copyright © 2023 Elsevier B.V.

Noorian, F., et al. (2023). "Are 7.5Gyx2 fractions more efficient than 6Gyx3 in postoperative endometrial cancer brachytherapy?" Radiotherapy and Oncology 182(Supplement 1): S1925-S1926.
	Purpose or Objective To compare two vaginal brachytherapy (VBT) fractionation schedules in postoperative endometrial carcinoma (PEC) patients considering vaginal-cuff control, late toxicities (vagina, rectum, and bladder), EQD2(a/b=3) received in the most exposed 2cm3 to dose in clinical target volume (CTV) and vaginal dilator use. Materials and Methods 110 PEC patients were treated with two VBT schedules from 2011 to 2021. The 110 patients fulfilled the inclusion criteria for exclusive brachytherapy and were analyzed in two groups: Group-1 included 44 patients treated with 3 fractions of 6 Gy from September 2011 to April 2014 and Group-2 included 66 patients treated with 2 fractions of 7.5 Gy from July 2015 to November 2021. The dose was prescribed at 5mm from the applicator surface with an active length of 2.5cm. CTV was delineated in all the patients and the EQD2(a/b=3) received in the most exposed 2cm3 to dose in CTV was calculated. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the LENT-SOMA objective criteria for vagina. Statistics: Descriptive analysis, Chi-square and Student's t tests. Results The median follow-up was 60 months (52.5-67.4) in Group-1 and 42.4 months (10.1-69.1) in Group-2. In the present study vaginal-cuff relapse and late toxicities in bladder and rectum were not found. 40 (39%) patients showed late vaginal toxicity: 21/44 (47.7%) patients in Group-1 (G1: 16 (36.4%), G2: 4 (10%), G3: 1 (2%)) and 19/66 (27.3%) patients in Group-2 (G1: 13 (18.2%) G2: 6 (9.1%)) (P=0.069). The mean EQD2(a/b=3) received by 2cm3 of the most exposed part of vagina was 63.7 Gy (SD+/-10.02) in Group-1 and 60.6 Gy (SD+/-3.90) in Group-2 (p= 0.066). Use of dilators > 9 months: 32 (72.7%) and 45 (68.2%) patients in Group 1 and 2, respectively (p=0.766). 12/44 (27.3%) patients in Group-1 and 21/66 (31.8%) in Group-2 used vaginal dilators (P= 0.766). Conclusion Despite the different fractionation schedules in PEC treatment, this is the first comparison of the present schedules. Considering the lack of vaginal relapses and the same vaginal toxicity rate in both groups, 2 fractions of 7.5 Gy seems more efficient in comparison to 3 fractions of 6 Gy in terms of patient comfort, work load and cost. However, further studies including more patients with a longer follow-up are required to confirm the present hypothesis.Copyright © 2023 Elsevier B.V.

Nora, G., et al. (2023). "The effectiveness of acupuncture on endometriosis-related pelvic pain or dysmenorrhea: a systematic review and meta-analysis."
	
Norby, N., et al. (2023). "Uterine Prolapse in Pregnancy: A Review." Obstetrical and Gynecological Survey 78(9): 537-543.
	Importance Although not a common occurrence, uterine prolapse during pregnancy can have significant effects for pregnancy outcomes and quality of life of maternal patients. Most data about management exist as case reports; a review of these cases provides some guidance about treatment options. Objectives This review examines current literature about uterine prolapse during pregnancy to assess current information about this condition, prevalence, diagnosis, management, and outcomes. Evidence Acquisition Electronic databases (PubMed and Embase) were searched using terms "uterine prolapse"AND "pregnancy"AND "etiology"OR "risk factors"OR "diagnosis"OR "therapy"OR "management"limited to the English language and between the years 1980 and October 31, 2022. Results Upon review of 475 articles, 48 relevant articles were included as well as 6 relevant articles found on additional literature review for a total of 54 articles. Of those articles, 62 individual cases of uterine prolapse in pregnancy were reviewed including pregnancy complications, mode of delivery, and outcomes. Prevalence was noted to be rare, but much more common in second and subsequent pregnancies. Most diagnoses were made based on symptomatic prolapse on examination. Management strategies included bed rest, pessary use, and surgery (typically during the early second trimester). Complications included preterm delivery, patient discomfort, urinary retention, and urinary tract infection. Delivery methods included both cesarean and vaginal deliveries. Conclusions Although a rare condition, uterine prolapse in pregnancy is readily diagnosed on examination. Reasonable conservative management strategies include observation, attempted reduction of prolapse, and pessary use; if these measures fail, surgical treatment is an option. Relevance Our review compiles literature and known cases of uterine prolapse during pregnancy and current evidence about prevalence, diagnosis, management, outcomes, and complications of uterine prolapse during pregnancy in order to inform our target audience in their clinical practice. Target Audience Obstetricians and gynecologist, family physicians. Learning Objectives After completing this learning activity, the participant should be able to describe the prevalence of uterine prolapse during pregnancy, potential at-risk populations, and presenting symptoms; identify management strategies for uterine prolapse during pregnancy including both surgical and conservative approaches; and assess possible complications of uterine prolapse during pregnancy.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Norfuad Farisha, A., et al. (2023). "Beneficial Effects of Probiotics on Benign Gynaecological Disorders: A Review." Nutrients 15(12).
	Probiotics are live microorganisms that confer beneficial effects on human health when an adequate dose is administered. Recently, the use of probiotics has gained tremendous interest from the public due to its promising effects in the management of various reproductive diseases. However, the review of probiotics' benefits on benign gynaecological disorders, including vaginal infections, polycystic ovary syndrome (PCOS) and endometriosis, remains scarce. Therefore, this review is built on current knowledge on the beneficial effects of probiotics against selected benign gynaecological disorders. Recent findings point out that probiotics' supplementation in different clinical and in vivo models showed promising health effects and results in the amelioration of disease symptoms. Thus, in this review, we showed the findings of both studies performed in clinical settings and animal studies. However, current information, solely based on clinical trials or animal studies, is inadequate in communicating the excellent findings on the beneficial effects of probiotics on human health. Therefore, future clinical intervention studies are required to further elucidate the evidence of the benefits of probiotics benefits regarding these gynaecological disorders.

Norman Jane, E., et al. (2021). "Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis." PLoS Medicine 18(3): e1003506.
	Background: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.; Methods and Findings: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55-1.38], p = 0.54). The primary neonatal outcome-a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery-was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54-1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50-1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.; Conclusions: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.; Trial Registration: ISRCTN Registry ISRCTN 02235181. ClinicalTrials.gov NCT02235181.; Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. JEN has received grants from government and charitable bodies for research into understanding the mechanism of term and preterm labour and understanding treatments. Within the last 3 years she has acted on a Data Safety and Monitoring Board for a study involving a preterm birth therapeutic agent for Glaxo Smith Kline, and has provided consultancy for Dilafor on drugs to alter labour progress. PRB reports personal fees from ObsEva Geneva, other from ObsEva Geneva, outside the submitted work; In addition, PRB has a patent PCT/GB1997/000529 WO1997031631 A1 Cox-2 selective inhibitors for managing labour and uterine contractions issued, a patent PCT/GB2004/001380 WO2005053705 A1 Use of a cyclopentenone prostaglandin for delaying the onset and/or preventing the continuation of labour (Priority Date Dec 2, 2003). issued, a patent PCT/GB2016/050618 Circulating miRNAs predictive of cervical shortening and preterm birth (Pending UK filing 6th March 2015 /Full international filing completed 7th March 2016). issued, a patent PCT/GB2016/050621 Rapid evaporative ionisation mass spectroscopy (REIMS) and Desorbtion Electrospray Ionisation Mass Spectroscopy (DESI-MS) analysis of swabs and b opsy samples. (Pending UK filing 6th March 2015 /Full international filing completed 7th March 2016 pending, a patent PCT/GB2019 Desorbtion Electrospray Ionisation Mass Spectroscopy (DESI-MS) analysis of swabs to predict vaginal microbiota. (Pending UK filing March 2019) pending, and a patent PCT/GB2019/Circulating miRNAs predictive of IUGR (Pending UK filing March 2019) pending. SCB reports grants from other from NIHR, NETSCC, HTA during the conduct of the study and personal fees and other from University of Copenhagen, Wellcome Trust, NIHR Global Health Research and French Cancer Institute outside the submitted work. SJS reports grants from NIHR HTA during the conduct of the study; being a member of the NIHR HTA General committee and receiving received other research funding from the NIHR (14/32/01 QUIDS), Wellcome Trust (209560/Z/17/Z) and CSO During the course of the study. SJS is a member of PLOS Medicine’s Editorial Board. NM reports personal fees from Shire-Takeda, personal fees from Novartis, personal fees from Glaxo-Smith-Klein, outside the submitted work. JN reports grants from University of Aberdeen and University of Edinburgh during the conduct of the study; and Membership of the following NIHR boards: CPR decision making committee; HTA Commissioning Board; HTA Commissioning Sub-Board (EOI); HTA Funding Boards Policy Group; HTA General Board; HTA Post-Board funding teleconference; NIHR CTU Standing Advisory Committee; NIHR HTA & EME Editorial Board; Pre-exposure Prophylaxis Impact Review Panel. ST has received grant funding from NIHR, other government and charity organisations. He provides commercial consultancy advice which has received financial compensation.

Nørregaard Line, B., et al. (2023). "Exercise training induces thrombogenic benefits in recent but not late postmenopausal females." American journal of physiology. Heart and circulatory physiology 325(2): H346-H361.
	Although regular physical activity is known to improve cardiovascular health in men, evidence for its beneficial effects in postmenopausal females is less convincing and it remains unclear whether initiation of exercise training soon after, rather than many years after menopause impacts the magnitude of training-induced adaptations. We evaluated exercise-induced changes in markers of thrombotic risk and conduit artery function in recent ≤5yr compared with late ≥10yr postmenopausal females. Fourteen recent ≤5yr and 13 late ≥10yr healthy postmenopausal females completed 8 wk of regular intensive exercise training, consisting of floorball and cycling. Markers of thrombotic risk and vascular health were assessed before and after the intervention, and data were analyzed using a linear mixed model. Exercise training reduced markers of thrombotic risk, including an 11% reduction ( P = 0.007) in agonist-induced platelet reactivity and a reduction ( P = 0.027) in incipient clot microstructure (∼40% reduction in clot mass) in the recent ≤5yr but not the late ≥10yr ( P = 0.380; P = 0.739, respectively) postmenopausal females. There was no change in conduit artery function, as measured by brachial (recent ≤5yr , P = 0.804; late ≥10yr , P = 0.311) and popliteal artery (recent ≤5yr , P = 0.130; late ≥10yr , P = 0.434) flow-mediated dilation. Only the late ≥10yr postmenopausal females exhibited an increase (by 9.6%, P = 0.022) in intracellular adhesion molecule-1 levels after training, which may have impacted the thrombogenic adaptation in this group. These findings suggest that 8 wk of high-intensity exercise training reduces thrombotic risk in recent ≤5yr , but not late ≥10yr postmenopausal females. Thus, regular physical activity initiated soon after, rather than many years after menopause and at a higher age, may be more efficient for reducing thrombogenic risk. NEW & NOTEWORTHY Eight weeks of high-intensity exercise training reduces platelet reactivity as well as blood clot density and strength in females ≤5 yr past menopause but not in females ≥10 yr past menopause. The divergent response in the late postmenopausal females may be explained by training-induced low-grade systemic inflammation. These findings suggest that regular physical activity initiated soon after menopause, compared with many years after menopause, may be more efficient for reducing the risk of blood clots.

Notaro Adriana Leal, G. and L. Neto Filipe Tenorio (2022). "The use of metformin in women with polycystic ovary syndrome: an updated review." Journal of Assisted Reproduction and Genetics 39(3): 573-579.
	Purposes: Polycystic ovary syndrome (PCOS) is a major cause of female infertility, being present in up to 20% of women of childbearing age. Insulin resistance (IR) plays an important role in the pathophysiology of PCOS; therefore, its treatment may benefit women with the syndrome. The main drug used for IR management is metformin (MT). We aim to review the literature on the use of metformin in women with PCOS.; Methods: Using the terms "metformin" and "polycystic ovary syndrome," we conducted a search the PubMed, EMBASE, and Google Scholar databases. The research was restricted to articles published in English. Initially, only published meta-analyses were included, in the absence of meta-analyzes, RCT and well-designed prospective studies were used.; Results: Metformin increases success rates and decreases complication rates when used as an adjunctive medication for ovulation induction during low complexity assisted reproduction treatments and during ovarian stimulation for in vitro fertilization in women with PCOS. Evidence about the effect of metformin on fetal and obstetric complication rates is conflicting. Metformin is associated with high incidence of gastrointestinal symptoms; however, serious adverse effects are rare and there is no evidence of teratogenicity.; Conclusion: For women with PCOS, metformin is a good adjunctive medication for ovulation induction/stimulation for high and low complexity assisted reproduction therapies. The adverse effects are mostly mild, and there is no risk of teratogenicity, but the risk of long-term complications for the offspring is not yet defined. High heterogeneity of the studies limits extrapolation of findings, and further research is needed to determine which women will benefit most from the medication. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Noushin, M. A., et al. (2021). "A comparative evaluation of subendometrial and intrauterine platelet-rich plasma treatment for women with recurrent implantation failure." F&S science 2(3): 295-302.
	OBJECTIVE: To compare the effectiveness of treatment with autologous activated platelet-rich plasma (PRP), administered to either the subendometrium (SE-PRP) or endometrial surface (intrauterine; IU-PRP), against controls. DESIGN: Prospective observational cohort study. SETTING: Tertiary fertility unit. PATIENTS: Women aged <40 years with a history of recurrent implantation failure undergoing frozen embryo transfer (FET) (n = 318). INTERVENTIONS: In SE-PRP, PRP was injected into the subendometrial space transvaginally in the luteal phase of the previous cycle of embryo transfer under ultrasound guidance (n = 55). In IU-PRP, PRP was administered during the index FET cycle when the endometrium was approximately 7 mm (n = 109). Both SE-PRP and IU-PRP groups were administered 300 μg of granulocyte colony-stimulating factor (G-CSF) subcutaneously once a day for 3 days to boost white blood cells (WBC) and growth factor production in the PRP sample. The control group consisted of women who did not choose PRP treatment and underwent standard FET with no intervention (n = 154). MAIN OUTCOME MEASURES: Ongoing pregnancy rate or live birth rate (OPR/LBR) per transfer cycle, clinical pregnancy rate (CPR) per transfer cycle, and miscarriage rate. RESULTS: As a result, OPR/LBR was higher in the SE-PRP (22/55, 40%) and IU-PRP (45/109, 41.3%) groups than that in the control group (34/154, 22.1%). It was similar between the SE-PRP and IU-PRP groups. Moreover, CPR showed a similar trend with a higher rate in the SE-PRP (28/55, 51%) and IU-PRP (57/109, 52.3%) groups than that in the controls (52/154, 33.8%). No statistical difference in the CPR was noted between the SE-PRP and IU-PRP groups. The miscarriage rate was similar in all three groups (14/55, 25.45%; 25/109, 22.23%; and 34/154, 22.07%, respectively). CONCLUSION: In women with a history of recurrent implantation failure, PRP treatment appears to improve FET outcome with an increase in OPR/LBR. However, SE-PRP treatment does not offer any advantage over lesser invasive IU-PRP treatment.

Noushin Majiyd, A., et al. (2021). "Dehydroepiandrosterone (DHEA) role in enhancement and maintenance of implantation (DREAM): randomised double-blind placebo-controlled trial-study protocol." BMJ Open 11(10): e054251.
	Introduction: Dehydroepiandrosterone (DHEA) is an important precursor of androgen and has been studied and researched extensively for improving the various outcome measures of ovarian stimulation in women with advanced age or poor ovarian response. Androgens also play an important role in the enhancement of endometrial and decidual function by regulating both the transcriptome and secretome of the endometrial stromal cells and have a positive effect on various factors like insulin-like growth factor binding protein 1, homeobox genes (HOXA10, HOXA11), secreted phosphoprotein 1, prolactin which are necessary for implantation. It is well-known that the circulating 'precursor pool' of DHEA declines with age more so in poor ovarian reserve patients and exogenous supplementation may be beneficial in such cases. This double-blinded randomised controlled trial (RCT) aims to test the hypothesis whether transient targeted supplementation of DHEA as an adjuvant to progesterone in frozen embryo transfer (FET) cycles, for women with low serum testosterone, helps in improving live birth rate.; Methods and Analysis: This study is planned as a double-blinded, placebo-controlled randomised trial and the sample size, calculated for the primary outcome measure-live birth rate, is 140. All participants will be having a flexible antagonist protocol for controlled ovarian stimulation and an elective freeze-all policy for the embryos as per the hospital protocol after written informed consent. For FET, the endometrium will be prepared by hormone replacement treatment protocol. During the FET cycle, the intervention group will be receiving DHEA 25 mg two times a day for 15 days from the day of starting progesterone supplementation and the control group will be receiving a placebo.; Ethics and Dissemination: The approval of the study was granted by the Clinical Trials Registry-India and the Institutional Ethical Committee of CRAFT Hospital and Research Center. All participants will provide written informed consent before being randomised into allocated treatment groups. The results will be disseminated to doctors and patients through conference presentations, peer-reviewed publications, social media and patient information booklets.; Trial Registration Numbers: CTRI/2020/06/025918; ECR/1044/Inst/KL/2018.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nova, H. and A. Nathalia (2023). "[Outcomes of post-abortion myometrial hypervascularization in the first trimester according to treatment: a systematic review] Desenlaces de la hipervascularización miometrial postaborto en primer trimestre según tratamiento: revisión sistemática."
	Objective: Determine the clinical outcomes in patients with enhanced myometrial vascularity following first trimester abortion according to the treatment, including expectant, medical, surgical intervention, or interventional radiology, through a systematic review of the literature. Methods: Women in the postabortion period of the first trimester with ultrasound-diagnosed enhanced myometrial vascularity from 2000 to 2023 were included. The authors evaluated the resolution of myometrial hypervascularization using 2D ultrasound and color Doppler and the presence of complications: myometrial infection, bleeding, hysterectomy, mortality, and the need for blood transfusion. PROSPERO registration: CRD42023410700. Results: a total of 364 studies were found in the initial search. Eleven studies with a population of 57 women were included. Treatments were either single or combined. The resolution of enhanced myometrial vascularity was 87.7% in the women included in the analysis. The time of resolution ranged from three days to seven months; 47.3% of the women achieved a subsequent pregnancy after diagnosis. Conclusion: Vaginal bleeding is the main complication. Therefore, clinical and ultrasound follow-up, along with timely therapeutic intervention, can reduce obstetric hemorrhage and maternal morbidity and mortality. Expectant management is proposed as the first-line treatment option, reserving interventional or surgical management for cases of persistent bleeding and/or hemodynamic instability. Objetivos: determinar los desenlaces clínicos en pacientes con hipervascularización miometrial postaborto en primer trimestre según el tratamiento instaurado: expectante, médico, quirúrgico o por radiología intervencionista mediante una revisión sistemática de la literatura. Métodos: se incluyeron mujeres en edad fértil en periodo postaborto del primer trimestre, con diagnóstico ecográfico de hipervascularización miometrial desde enero de 2000 a febrero de 2023. Los autores evaluaron la resolución de la hipervascularización miometrial mediante ultrasonografía 2D y Doppler color y la presencia de complicaciones como infección miometrial, volumen de sangrado, histerectomía, mortalidad materna, necesidad de transfusión de hemoderivados. La información fue resumida de manera cualitativa de acuerdo a lo presentado por los autores. Registro PROSPERO CRD42023410700. Resultados: de 364 estudios encontrados en la búsqueda inicial, se incluyeron once estudios con una población de 57 mujeres. La incidencia reportada fue del 1,52%. Los tratamientos fueron únicos o combinados. Se encontró una resolución de la hipervascularización miometrial en el 87,7% de las mujeres incluidas en el análisis. El tiempo de resolución osciló entre tres días hasta siete meses. El 47,3% de las mujeres lograron un embarazo posterior al diagnóstico. Conclusión: La hipervascularización miometrial postaborto es subdiagnosticada con un vacío en la evidencia en su tratamiento. El sangrado vaginal es la principal complicación por lo que el seguimiento clínico, ecográfico y el abordaje terapéutico oportuno puede reducir la hemorragia obstétrica y la morbimortalidad materna. El manejo expectante se plantea como primera alternativa de tratamiento; se reserva el manejo intervencionista o quirúrgico para casos de sangrado persistente y/o inestabilidad hemodinámica.

Novara, G., et al. (2020). "Telehealth in Urology: A Systematic Review of the Literature. How Much Can Telemedicine Be Useful During and After the COVID-19 Pandemic?" European Urology 78(6): 786-811.
	Context: Coronavirus disease 2019 (COVID-19) pandemic has caused increased interest in the application of telehealth to provide care without exposing patients and physicians to the risk of contagion. The urological literature on the topic is sparse.; Objective: To perform a systematic review of the literature and evaluate all the available studies on urological applications of telehealth.; Evidence Acquisition: After registration on PROSPERO, we searched PubMed and Scopus databases to collect any kind of studies evaluating any telehealth interventions in any urological conditions. The National Toxicology Program/Office of Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies was used to estimate the risk of bias. A narrative synthesis was performed.; Evidence Synthesis: We identified 45 studies (11 concerning prostate cancer [PCa], three hematuria management, six urinary stones, 14 urinary incontinence [UI], five urinary tract infections [UTIs], and six other conditions), including 12 randomized controlled trials. The available literature indicates that telemedicine has been implemented successfully in several common clinical scenarios, including the decision-making process following a diagnosis of nonmetastatic PCa, follow-up care of patients with localized PCa after curative treatments, initial diagnosis of hematuria, management diagnosis and follow-up care of uncomplicated urinary stones and uncomplicated UTIs, and initial evaluation, behavioral therapies, and pelvic floor muscle training in UI patients, as well as follow-up care after surgical treatments of stress urinary incontinence or pelvic organ prolapse. The methodological quality of most of the reports was good.; Conclusions: Telehealth has been implemented successfully in selected patients with PCa, UI, pelvic organ prolapse, uncomplicated urinary stones, and UTIs. Many urological conditions are suitable for telehealth, but more studies are needed on other highly prevalent urological malignant and benign conditions. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine. More robust data on long-term efficacy, safety, and health economics are necessary.; Patient Summary: The diffusion of coronavirus disease 2019 (COVID-19) infections has recently increased the interest in telehealth, which is the adoption of telecommunication to deliver any health care activity. The available literature indicates that telemedicine has been adopted successfully in selected patients with several common clinical urological conditions, including prostate cancer, uncomplicated urinary stones, uncomplicated urinary infections, urinary incontinence, or pelvic organ prolapse. Likely, the COVID-19 pandemic will give a significant boost to the use of telemedicine, but more robust data on long-term efficacy, safety, and costs are necessary. (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Novoa-Vargas, A., et al. (2022). "Ovarian borderline tumor: Review of an old acquaintance with new therapeutic proposals." Ginecologia y Obstetricia de Mexico 90(3): 261-272.
	BACKGROUND: Patients with borderline ovarian tumor can be treated conservatively in early stages and thereby achieve considerable survival. Advanced stages have a prolonged disease-free period, some with peritoneal implant growth and relapse after 10 years of treatment. OBJECTIVE(S): To know the prognosis of patients with borderline ovarian tumor and its treatment in Mexico and other countries. METHODOLOGY: Systematic review of recent clinical trials registered in PubMed, Embase and Cochrane databases of articles published in English and Spanish between 2006 and 2021. In addition, an analytical review of the experience accumulated in 10 years in the care of patients with borderline ovarian tumor attended at the Oncology High Specialty Medical Unit of the XXI Century National Medical Center of the Mexican Social Security Institute, in Mexico City and other medical centers in the Mexican Republic. RESULT(S): We found 62 articles related to the search terms; of these, 11 were discarded because they were not original articles only on ovarian borderline tumors and 4 because the full text was written in languages other than English and Spanish. One more was eliminated because its conclusions differed from the stated objective and its support was considered weak. In the end, 41 articles were analyzed. CONCLUSION(S): The chances of surgical care of patients with ovarian borderline tumor, with fertility preservation, are high because its recurrence is low. Mucinous microinvasive tumors, with vascular and lymphatic permeation, will have a higher chance of long-term relapse. In general, their prognosis for survival, at each stage, is high. Retroperitoneal lymphadenectomy is not indicated in early stages of the disease.Copyright © 2022 Asociacion Mexicana de Ginecologia y Obstetricia. All rights reserved.

Nowakowski, Ł., et al. (2023). "Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery." Menopause (New York, N.Y.) 30(6): 629-634.
	Objective: Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery.; Method: Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed.; Results: Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed.; Conclusions: The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.; Competing Interests: Financial disclosures/conflicts of interest: None reported. (Copyright © 2023 by The North American Menopause Society.)

Nuersimanguli, m., et al. (2021). "Efficacy of Endostar combined with chemoradiotherapy in advanced cervical cancer: systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Nugawela, D. and L. Gorringe Kylie (2023). "Targeted therapy for mucinous ovarian carcinoma: evidence from clinical trials." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(1): 102-108.
	Mucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer. Despite being a chemoresistant tumour type, surgical resection and chemotherapy are still the current standard for management. This narrative review aims to explore the current evidence for targeted therapies in mucinous ovarian carcinoma. A review of the literature was performed to identify clinical trials and case reports of targeted therapy in patients with mucinous ovarian carcinoma. The databases and registers (PubMed, MEDLINE, Embase, Europe PMC, Cochrane Central Register of Clinical Trials, clinicaltrials.gov) were searched for articles published between January 2009 to June 2021 using keywords specific for mucinous ovarian carcinoma and targeted therapy. Records were screened and assessed for eligibility based on inclusion and exclusion criteria. From 684 records, 21 studies met the criteria to be included in the review. A total of 11 different targeted therapies were identified, each demonstrating varying degrees of clinical evidence supporting further investigation in patients with mucinous ovarian carcinoma. Targeted therapies identified in this review that warrant further investigations are bevacizumab, trastuzumab, nintedanib, AZD1775, sunitinib, cediranib and pazopanib. Many of the therapeutic agents may be investigated further in combination with other targeted therapies or chemotherapy. More clinical trials focusing on targeted therapy specifically in patients with mucinous ovarian cancer are required to inform clinical use. Multinational efforts are likely to be required to successfully conduct trials in this rare tumor type.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. Re-use permitted under CC BY. Published by BMJ.)

Nunes, J. M. O., et al. (2023). "Transcutaneous tibial nerve electrical stimulation versus vaginal electrical stimulation in women with overactive bladder syndrome: Is there a role for short-term interventions?" Neurourology and Urodynamics 42(5): 1101-1110.
	OBJECTIVE: To assess the efficacy of vaginal electrical stimulation (VS) versus transcutaneous tibial nerve electrical stimulation (TTNS) in women with overactive bladder syndrome (OAB). MATERIAL AND METHODS: Sixty-nine patients were randomized to receive 12 sessions of VS versus TTNS, or no treatment (control group-CG), over 6 weeks. OAB impact according to international consultation on incontinence questionnaire overactive bladder module (ICIQ-OAB), symptoms discomfort scores and voiding diaries were evaluated at baseline, 6 weeks and 1-month post-treatment. RESULTS: Both TTNS (mean difference = -4.2; 95% confidence interval [CI] = -6.5 to -1.9) and VS (-3.8; -6.0 to -1.6) were associated with significant reduction of ICIQ-OAB scores, as well as discomfort sensation (-3.9; -6.2 to -1,7; p < 0.001 for the TTNS and -2.8; -5.0 to -0.6; p = 0.01 for the VS) at 6 weeks when compared to CG (p < 0.001). ICIQ-OAB score remained low only in the TTNS group when compared to the CG (-3.6; -6.0 to -1.2/p = 0.00) 1 month after treatment. Discomfort symptoms improved in both active groups when compared to CG (TTNS [-3.2; -5.2 to -1.2; p < 0.001] and VS groups [-2.6; -4.7 to -0.6; p = 0.01]). No statistically differences were found in primary outcomes comparing TTNS and VS Secondary analysis showed significant improvement in urinary urgency incontinence episodes (UUI) in both TTNS and VS, but CG. UUI episodes were still reduced in the VS group and urgency in the TTNS group 1-month post-treatment. CONCLUSION: Short-term interventions (6 weeks) of TTNS and VS were both effective in treating women with OAB. TTNS provided residual effects at one-month postintervention on ICIQ-OAB score.

Nurturely (2023). Carrying for the Culture.
	No Results Available Device: Infant Carrier Depression Scale Score of Each Participant|Number of Weeks of Lactation of Each Participant|Proportion of Parents who Exclusively Breastfed their Infant|Lactation Frequency of Each Participant|Cultural Models of Infant Care Score of Each Participant|Average Crying Frequency of Infant|Participant Breastfeeding Self-Efficacy Score|Participant Ability to Access Human Milk Score|Participant Responsiveness to Infant Feeding Cues Score|Mother to Infant Bonding Scale Score Female Not Applicable 400 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 23 December 2028

Nyirjesy, P., et al. (2022). "Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 74(12): 2129-2135.
	Background: Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis.; Methods: Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10).; Results: Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events.; Conclusions: Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis.; Clinical Trials Registration: NCT03253094. (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Nyirjesy, P. and D. Sobel Jack (2019). "Re: A systematic review of drug treatment of vulvodynia: evidence of a strong placebo effect." BJOG : an international journal of obstetrics and gynaecology 126(7): 945-946.
	
Oadi, S., et al. (2023). "Curcumin, a bioactive supplement for Premenstrual Syndrome and Dysmenorrhea- A Systematic Review of randomized clinical trials."
	
Oaknin, A., et al. (2022). "EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer." European journal of cancer (Oxford, England : 1990) 174: 299-309.
	Background: In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study.; Methods: Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1-16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy.; Results: Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77-13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08-12.62; P &lt; 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations.; Conclusions: Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.; Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.O. reports serving on advisory boards for Roche, AstraZeneca, MSD/Merck, PharmaMar, Clovis Oncology, Tesaro, Immunogen, Genmab, Mersana Therapeutic, GSK, SUTRO, AGENUS and Deciphera Pharmaceuticals; and support for travel or accommodation from Roche, AstraZeneca and PharmaMar. B.J.M. reports consulting honoraria from Aravive, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Conjupro Biotherapeutics, Eisai, Geistlich, Genmab/Seattle Genetics, Gynecologic Oncology Group Foundation, Immunogen, Immunomedics, Incyte, Laekna Health Care, Mateon/Oxigene, Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Precision Oncology, Puma, Regeneron, Samumed, Takeda, VBL and Vigeo; and consulting or speaker honoraria from AstraZeneca, Clovis, Janssen/Johnson & Johnson, Roche/Genentech and Tesaro/GSK. I.V. reports consulting fees from AstraZeneca, Elevar Therapeutics, Genmab, GSK, Immunogen, Merck Sharp & Dohme and Oncoinvent; and contracted research from Genmab and Hoffmann-La Roche. A.C.M. has served on advisory boards for Merck Sharp & Dohme, Bristol-Myers Squibb and Libbs; has received support for travel or accommodation from AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb and Roche; and reports institutional research grant support from Clovis Oncology, Bristol-Myers Squibb, Roche, Novartis, Amgen, Merck Sharp & Dohme, Lilly, Pierre Fabre, Sanofi and Pfizer. Y.M.K. reports ownership of stock at Johnson & Johnson and Genolution for self and spouse; consulting or advisory role at Merck Sharp & Dohme; and research funding from Regeneron Pharmaceuticals, Inc., and Roche. A.S.L., V.S., H.S.K., E.A.G., F.D. and C.-L.C. declare no conflict of interest. S.T. reports honoraria from Daiichi Sankyo, Eisai, Bayer, Taiho Pharmaceutical, Merck Sharp & Dohme, Novartis, Chugai Pharma, AstraZeneca, Bristol-Myers Squibb Japan, Ono Pharmaceutical, Niho kayaku, Pfizer and Lilly Japan; advisory role at Bayer; research funding from Daiichi Sankyo, Sanofi, Eisai, Bayer, Taiho Pharmaceutical, Merck Sharp & Dohme, Novartis, Chugai Pharma, AstraZeneca, Bristol-Myers Squibb, Lilly, Ono Pharmaceutical, PharmaMar and Pfizer/EMD Serono; and travel, accommodation and expenses from Daiichi Sankyo and Novartis. J.L., M.M., M.G.F., I.L., J.H. and C.C. are employees and shareholders of Regeneron Pharmaceuticals, Inc. C.I. and M.R. report employment at IQVIA and institutional research funding from Regeneron Pharmaceuticals, Inc. P.R.L. is an employee of, and may hold shares and stock options in Sanofi. K.T. reports honoraria from Tesaro and Clovis Oncology; consulting or advisory roles for Genentech, Tesaro, Clovis and AstraZeneca; serving on a speaker's bureau for Genentech, AstraZeneca, Merck, Tesaro and Clovis; institutional research funding from AbbVie, Genentech, Morphotek, Merck and Regeneron Pharmaceuticals, Inc.; and travel, accommodation and expenses from Genentech. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Oberg, E. (2023). "Effects of lifestyle intervention in overweight women with polycystic ovary syndrome-aspects on reproduction, metabolism, psychological well-being and sleep." Dissertation Abstracts International: Section B: The Sciences and Engineering 84(4-B): No-Specified.
	Polycystic Ovary Syndrome, or PCOS, is the most common hormonal disturbance in women of a childbearing age, with up to one in ten women being affected. Some of the most common symptoms relate to the menstrual period with irregular or even absent periods and many women have difficulties falling pregnant. Women with PCOS often have raised levels of androgens in the blood. Androgens are sex-hormones, sometimes referred to as "male" hormones, although they are also normally present in women but in lower quantities. Testosterone is an example of an androgen. The raised levels of androgens can result in symptoms such as increased body hair often on the stomach, chest or back as well as acne. There are other problems associated with PCOS as well, such as type 2 diabetes, increased weight often located to the abdomen, increased cholesterol and levels of inflammation. In addition, women with PCOS are more likely to suffer from depression, anxiety and they often have a worse quality of life. We do not know exactly what causes PCOS but we think a combination of genetic and lifestyle factors are involved.The recommended first-line treatment for PCOS is to improve the lifestyle by healthy eating, exercising or through some kind of behavioral change program that would lead to a healthier lifestyle. Previous studies have shown that weight loss, even as little as 5% - 10% can lead to normalized menstrual periods and therefore for the fertility to come back. In fact, the majority of PCOS symptoms improve when losing weight. Other treatment options for women with PCOS include the contraceptive pill, which can lower the levels of androgens and therefore improve the symptoms, as well as controlling the irregular periods. Sometimes diabetes medication, such as metformin, is used. Furthermore, women with PCOS might also need fertility treatment. We know that being over-weight increases the risk of miscarriage and also that pregnancies in over-weight mothers are more likely to involve complications for both the mother and the child. This is why in many countries, Sweden being one of them, there is an upper weight limit of body mass index (BMI) of 30-35 kg/m2 to be able to access state funded and often even privately funded fertility treatment. This result in a large group of obese women with PCOS who do not qualify for fertility treatment.This study set out to investigate if changing the lifestyle trough an intervention focusing on the study participants behavior would have an effect on the symptoms such as menstrual regularity, weight, levels of androgens such as testosterone, psychological well-being, sleep quality and inflammation. The women taking part in the study were 68 overweight or obese women with PCOS that were otherwise healthy and did not take any regular medication. Study participants were randomly allocated to receive either the intervention or to control treatment. The intervention was a four-month long course that included weekly meetings in small groups with a course leader/ lifestyle coach as well as individual meetings with the coach every three weeks where the personal progress was reviewed. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Oberg, E., et al. (2023). "Different sleep pattern in over-weight/obese women with polycystic ovary syndrome." Frontiers in Endocrinology 14: 1068045.
	Context: Sleep duration and sleep quality have important health implications although our knowledge of objectively measured sleep variables in women with Polycystic Ovary Syndrome (PCOS) is limited.; Objective: To compare sleep variables assessed by actigraphy in over-weight/obese women with PCOS and controls, and to assess sleep variables after behavioral modification intervention in comparison with minimal intervention in a randomized trial.; Design: Randomized controlled trial, and a control group.; Setting: Outpatient gynecological clinic at a university hospital in Sweden.; Participants: 39 women fulfilling all Rotterdam PCOS criteria, randomized to behavioral modification intervention or minimal intervention and 21 controls with no other metabolic disease, all aged 18-40 years with a BMI ≥ 27 kg/m 2 .; Intervention: A four-month behavioral modification intervention including weekly group meetings focusing on behavioral and healthy lifestyle aspects. Minimal intervention reflecting standard care.; Main Outcome Measure: Sleep durations and sleep efficiency assessed by actigraphy.; Results: Compared to the control group, women with PCOS had significantly shorter time in bed (501 vs 548 min, p= 0.049), sleep time over 24 hours (448 vs 567 min, p=0.005) and sleep time at night (434 vs 511 min, p=0.002), poorer sleep efficiency (87 vs 93%, p<0.001), and longer wakefulness after sleep onset (64 vs 38 min, p<0.001). However, total sleep time at night for women with PCOS (7.2hrs) was within the normal range. Following behavioral modification intervention, the reduction from baseline in sleep over 24 hours and in the daytime sleep were significant compared to the minimal intervention group (78 min, p=0.009 and 43 min, p=0.003 respectively).; Conclusions: We found over-weight/obese women with PCOS to have normal sleep duration, but worse sleep efficiency than controls. Behavioral modification intervention seems to reduce the amount of daytime sleep, suggesting improved sleep behavior.; Clinical Trials Registration: https://doi.org/10.1186/ISRCTN48947168, identifier ISRCTN48947168.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Oberg, Blomberg, Åkerstedt and Hirschberg.)

Obermair, A., et al. (2021). "A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer - ENDO-3: ANZGOG trial 1911/2020." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(12): 1595-1601.
	BACKGROUND: Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. PRIMARY OBJECTIVES: Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. STUDY HYPOTHESIS: The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. TRIAL DESIGN: This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer; clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. PRIMARY ENDPOINTS: The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. SAMPLE SIZE: 760 participants (both stages). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. TRIAL REGISTRATION: NCT04073706.

Obermair Helena, M., et al. (2021). "Paucity of data evaluating patient centred outcomes following sentinel lymph node dissection in endometrial cancer: A systematic review." Gynecologic Oncology Reports 36: 100763.
	Sentinel lymph node dissection (SLND) is presently used by the majority of gynaecologic oncologists for surgical staging of endometrial cancer. SLND assimilated into routine surgical practice because it increases precision of surgical staging and may reduce morbidity compared to a full, systematic LND. Previous research focussed on the accuracy of SLND. Patient centred outcomes have never been conclusively demonstrated. The objective of this systematic review was to evaluate patient centred outcomes of SLND for endometrial cancer patients. Literature published in the last five years (January 2015 to April 2020) was retrieved from PubMed, EMBASE, and Cochrane library, across five domains: (1) perioperative outcomes; (2) adjuvant treatment; (3) patient-reported outcomes (PROs); (4) lymphedema, and (5) cost. Covidence software ascertained a standardised and monitored review process. We identified 21 eligible studies. Included studies were highly heterogeneous, with widely varying outcome measures and reporting. SLND was associated with shorter operating times and lower estimated blood loss compared to systematic LND, but intra-operative and post-operative complications were not conclusively different. There was either no impact, or a trend towards less adjuvant treatment used in patients with SLND compared to systematic LND. SLND had lower prevalence rates of lymphedema compared to systematic LND, although this was shown only in three retrospective studies. Costs of surgical staging were lowest for no node sampling, followed by SLND, then LND. PROs were unable to be compared because of a lack of studies. The quality of evidence on patient-centred outcomes associated with SLND for surgical staging of endometrial cancer is poor, particularly in PROs, lymphedema and cost. The available studies were vulnerable to bias and confounding. Registration of Systematic Review: PROSPERO (CRD42020180339). (© 2021 The Authors. Published by Elsevier Inc.)

Obikane, E., et al. (2021). "Internet-based behavioural activation to improve depressive symptoms and prevent child abuse in postnatal women (SmartMama): a protocol for a pragmatic randomized controlled trial." BMC Pregnancy and Childbirth 21(1): 314.
	Background: Child abuse and postnatal depression are two public health problems that often co-occur, with rates of childhood maltreatment highest during the first year of life. Internet-based behavioural activation (iBA) therapy has demonstrated its efficacy for improving postnatal depression. No study has examined whether the iBA program is also effective at preventing child abuse. This study aims to investigate whether iBA improves depressive symptoms among mothers and prevents abusive behaviours towards children in postpartum mothers in a randomized controlled trial, stratifying on depressive mood status. The study also evaluates the implementation aspects of the program, including how users, medical providers, and managers perceive the program in terms of acceptability, appropriateness, feasibility, and harm done.; Methods: The study is a non-blinded, stratified randomized controlled trial. Based on cut-off scores validated on Japanese mothers, participants will be stratified to either a low Edinburgh Postnatal Depression Scale (EPDS) group, (EPDS 0-8 points) or a high EPDS group (EPDS ≥9 points). A total of 390 postnatal women, 20 years or older, who have given birth within 10 weeks and have regular internet-access will be recruited at two hospitals. Participants will be randomly assigned to either treatment, with treatment as usual (TAU) or through intervention groups. The TAU group receives 12 weekly iBA sessions with online assignments and feedback from trained therapists. Co-primary outcomes are maternal depressive symptoms (EPDS) and psychological aggression toward children (Conflict Tactic Scale 1) at the 24-week follow-up survey. Secondary outcomes include maternal depressive symptoms, parental stress, bonding relationship, quality of life, maternal health care use, and paediatric outcomes such as physical development, preventive care attendance, and health care use. The study will also investigate the implementation outcomes of the program.; Discussion: The study investigates the effectiveness of the iBA program for maternal depressive symptoms and psychological aggression toward children, as well as implementation outcomes, in a randomized-controlled trial. The iBA may be a potential strategy for improving maternal postnatal depression and preventing child abuse.; Trial Registration: The study protocol (issue date: 2019-Mar-01, original version 2019005NI-00) was registered at the UMIN Clinical Trial Registry (UMIN-CTR: ID UMIN 000036864 ).

O'Brien, L., et al. (2023). "Conservative surgery versus colorectal resection for endometriosis with rectal involvement: a systematic review and meta-analysis of surgical and long-term outcomes." International Journal of Colorectal Disease 38(1): 55.
	Purpose: The optimal surgical approach for removal of colorectal endometrial deposits is unclear. Shaving and discoid excision of colorectal deposits allow organ preservation but risk recurrence with associated functional issues and re-operation. Formal resection risks potential higher complications but may be associated with lower recurrence rates. This meta-analysis compares peri-operative and long-term outcomes between conservative surgery (shaving and disc excision) versus formal colorectal resection.; Methods: The study was registered with PROSPERO. A systematic search was performed on PubMed and EMBASE databases. All comparative studies examining surgical outcomes in patients that underwent conservative surgery versus colorectal resection for rectal endometrial deposits were included. The two main groups (conservative versus resection) were compared in three main blocks of variables including group comparability, operative outcomes and long-term outcomes.; Results: Seventeen studies including 2861 patients were analysed with patients subdivided by procedure: colorectal resection (n = 1389), shaving (n = 703) and discoid excision (n = 742). When formal colorectal resection was compared to conservative surgery there was lower risk of recurrence (p = 0.002), comparable functional outcomes (minor LARS, p = 0.30, major LARS, p = 0.54), similar rates of postoperative leaks (p = 0.22), pelvic abscesses (p = 0.18) and rectovaginal fistula (p = 0.92). On subgroup analysis, shaving had the highest recurrence rate (p = 0.0007), however a lower rate of stoma formation (p < 0.00001) and rectal stenosis (p = 0.01). Discoid excision and formal resection were comparable.; Conclusion: Colorectal resection has a significantly lower recurrence rate compared to shaving. There is no difference in complications or functional outcomes between discoid excision and formal resection and both have similar recurrence rates. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Obrzut, B., et al. (2022). "Laparoscopic in-bag morcellation - a comparison of two tissue extraction systems." Ginekologia polska 93(5): 369-373.
	Objectives: Morcellation is an integral part of laparoscopic procedures related to uterine fibroids, which consist of the mechanical fragmentation of the tumor and its extraction outside the abdominal cavity. To avoid the risk of tissue dissemination, special extraction systems have been developed, which allow morcellation of the specimen under visual control and its removal without contact with the abdominal organs. The aim of the paper is to compare the two systems for laparoscopic morcellation.; Material and Methods: The study included 33 premenopausal women with symptomatic leiomyomas or adenomyosis, who were qualified for laparoscopic surgery with contained power morcellation. Patients were allocated alternately to a different tissue extraction system's group. According to the study protocol, selected operative parameters were prospectively recorded. Finally, an assessment of bag use was performed. The data was statistically analyzed.; Results: There were significant differences between the two tested systems in terms of introducing and positioning the bag, its removal from the peritoneal cavity, as well as optic trocar insertion and establishing the pseudo-peritoneum.; Conclusions: Despite the minor design differences and some ergonomic aspects, both presented systems proved to be safe and feasible tools for laparoscopic contained morcellation. This technique both reduces the risk of tissue dissemination and preserves the advantages of minimal invasiveness.

Ochoa, W., et al. (2021). "A randomized control trial of using baby books to reduce new mothers' feelings of stress and depression." Maternal and Child Health Journal 25(10): 1615-1625.
	Objective: To determine whether embedding educational information about child development and optimal parenting practices from the Bright Futures Guidelines for Health Supervision into baby books can reduce women's depressive symptoms and parenting stress during the first 18 months of motherhood. Methods: A sample of 167 low-income, primarily African-American, first-time mothers were randomized into three conditions while pregnant: an educational book group, a non-educational book group, or a no-book group. Depressive symptoms and parenting stress were assessed using two questionnaires during home visits when women were in their third trimester of pregnancy (baseline) and when their child was 2, 4, 6, 9, 12, and 18 months of age. Results: Hierarchical Linear Models showed that women who received books with educational information shed depressive symptoms and parenting stress at a faster rate than women who received similar books without educational information and women who did not receive books. Conclusions: These findings indicate that providing women with child development and parenting information via baby books can be an effective strategy for promoting new mothers' emotional wellbeing. Since feelings of sadness and stress are risky for both mothers and their infants, this easy to implement intervention holds great promise. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Octubre Hospital Regional 1o, d., et al. (2021). Comparison of Fluoxetine Versus Citalopram Therapy to Control Postmenopausal Vasomotor Syndrome.
	No Results Available Drug: Fluoxetine 20 MG|Drug: Citalopram 20mg Change from baseline Menopause Rating Scale (MRS) total score at 3 months|Change from baseline Menopause Rating Scale (MRS) total score at 6 months|Change from baseline Menopause Rating Scale (MRS) somatic domain score at 3 months|Change from baseline Menopause Rating Scale (MRS) somatic domain score at 6 months|Change from baseline Menopause Rating Scale (MRS) urogenital domain score at 3 months|Change from baseline Menopause Rating Scale (MRS) urogenital domain score at 6 months|Change from baseline Menopause Rating Scale (MRS) psychological domain score at 3 months|Change from baseline Menopause Rating Scale (MRS) psychological domain score at 6 months|Change from baseline score in Item 1 of the Menopause Rating Scale (MRS) at 3 months|Change from baseline score in Item 1 of the Menopause Rating Scale (MRS) at 6 months|Change from the severity of individual Menopause Rating Scale (MRS) items at 6 months Female Not Applicable 91 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 122.2021 December 20, 2021

Odejinmi, F. and R. Mallick (2019). "Pregnancy Outcomes Following Ulipristal Acetate for Uterine Fibroids: A Systematic Review." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 41(1): 13.
	
Oderkerk Tamara, J., et al. (2022). "Endometrial ablation plus levonorgestrel releasing intrauterine system versus endometrial ablation alone in women with heavy menstrual bleeding: study protocol of a multicentre randomised controlled trial; MIRA2 trial." BMC Women's Health 22(1): 257.
	Background: It is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation. In these ways, insertion of an LNG-IUS immediately after endometrial ablation might prevent subsequent hysterectomies because of persisting uterine bleeding and cyclical pelvic pain or pain that arises de novo. Hence, we evaluate if the combination of endometrial ablation and an LNG-IUS is superior to endometrial ablation alone in terms of reducing subsequent rates of hysterectomy at two years following the initial ablative procedure.; Methods/design: We perform a multicentre randomised controlled trial in 35 hospitals in the Netherlands. Women with heavy menstrual bleeding, who opt for treatment with endometrial ablation and without contraindication for an LNG-IUS are eligible. After informed consent, participants are randomly allocated to either endometrial ablation plus LNG-IUS or endometrial ablation alone. The primary outcome is the hysterectomy rate at 24 months following endometrial ablation. Secondary outcomes include women's satisfaction, reinterventions, complications, side effects, menstrual bleeding patterns, quality of life, societal costs.; Discussion: The results of this study will help clinicians inform women with HMB who opt for treatment with endometrial ablation about whether concomitant use of the LNG-IUS is beneficial for reducing the need for hysterectomy due to ongoing bleeding and/or pain symptoms. Trial registration Dutch Trial registration: NL7817. Registered 20 June 2019, https://www.trialregister.nl/trial/7817 . (© 2022. The Author(s).)

Oe, K., et al. (2022). "S-Equol improves the quality of life for postmenopausal healthy women with complaints from aging." Menopause 29(12): 1478.
	Objective: S-Equol is known as a substance produced from soy isoflavone, daidzein, by intestinal bacteria. It exhibits a higher estrogen-like activity than daidzein (1). The transformation of daidzein to equol by the intestinal microflora widely differs among individuals, depending on their eating and lifestyle habits. Those who have the equolproducing bacteria in their intestinal flora are known to alleviate menopausal symptoms, maintain bone density, reduce the risk of breast, prevent skin aging, and reduce the risk of dementia and lifestyle-related diseases (2, 3). We evaluated the effect of S-Equol on quality of life (QOL) and its safety in postmenopausal healthy women. Design(s): A randomized, double-blind, placebo-controlled, parallel-group comparative study was carried out with 59 postmenopausal healthy Japanese women (40 -65 years) who experienced discomforts associated with female hormone decline and who did not produce equol. Subjects were divided into two groups, a test food (capsule containing 5 mg of S-equol) group (30 subjects) and a placebo food group (29 subjects). Each group ingested 2 capsules daily for 12 weeks. Quality of life was evaluated using the anti-aging QOL common questionnaire (4) at 0, 4, 8, and 12 weeks. Result(s): The test food group that was studied significantly improved conditions compared to the placebo food group in multiple items of the questionnaire. The items included Underweight, Constipation, Cold sensitivity, Not motivated, Not feeling happy, Not enjoying daily life, Lost confidence, Sociability, Self-affirmation, Worry, Stiff shoulders, Dull, Loss of appetite, and Stomachache. No significant differences were observed in blood pressure and pulse, body weight, percentage body fat, BMI, hematological test, blood biochemical test, endocrinological test, and general urine test between the two groups after 12 weeks Conclusion(s): It was concluded that daily intake of 10 mg of S-equol for 12 weeks may improve problems associated with aging and contribute to the improvement of QOL.

Offiah, I., et al. (2021). "Long-term efficacy and complications of a multicentre randomised controlled trial comparing retropubic and transobturator mid-urethral slings: a prospective observational study." BJOG : an international journal of obstetrics and gynaecology 128(13): 2191-2199.
	OBJECTIVE: There are concerns regarding the risks of mid-urethral slings (MUS) for stress urinary incontinence (SUI), particularly because of the lack of long-term data. We compare patient-reported outcomes of a multicentre randomised controlled trial of retropubic (TVT, GYNECARE™) versus transobturator (TOT, MONARC™) tape surgery at 12 years. DESIGN AND SETTING: A multicentre study was performed in 11 tertiary referral centres. POPULATION: A cohort of 180 participants from the original trial, the majority of whom had mixed urinary incontinence. METHODS: Postal questionnaire survey of patient-reported outcome measures using the International Consultation on Incontinence Questionnaire, Patient Global Impression of Improvement questionnaire (PGI-I) and a numeric rating scale pain questionnaire. MAIN OUTCOME MEASURES: Comparison of the efficacy and complications between the TVT and TOT procedures in the long term. RESULTS: A total of 110/180 responses were received: 55 for TVT and 55 for TOT. The mean follow-up was 12.8 ± 0.29 years (SD). TVT was significantly superior to TOT: 41.8% TVT with no SUI, versus 21.8% TOT (P = 0.04). Urgency urinary incontinence (UUI) was the most bothersome urinary symptom: 14.5% of respondents reported UUI after TVT and TOT. This was an improvement from the baseline levels: 61.8% TVT and 76.4% TOT. Seventeen patients (9 TVT and 8 TOT) out of 121 reported moderate or severe pain with severe pain in 3 with TVT and 2 with TOT. Overall, 80% TVT and 77% TOT participants reported their symptoms as improved on the PGI-I. CONCLUSIONS: TVT is superior to TOT for SUI cure. Efficacy is reduced by 12 years. There is low incidence of severe vaginal or groin pain. Careful patient counselling on long-term outcomes is required. The Retropubic tape appears to be an effective treatment for the majority of women with SUI. TWEETABLE ABSTRACT: Retropubic tape has superior efficacy to transobturator tape. Complications are comparable with low rates.

Oh, J., et al. (2023). "Monitored Anesthesia Care in Uterine Artery Embolization for Leiomyomas and Adenomyosis." Clinical and Experimental Obstetrics and Gynecology 50(2): 26.
	Background: Patients undergoing an interventional radiology procedure report some degree of anxiety. Therefore, procedure-related anxiety needs to be managed. The aim of our study was to investigate patient satisfaction with monitored anesthesia care (MAC) for uterine artery embolization (UAE)-related procedural anxiety in symptomatic uterine fibroids or adenomyosis. Method(s): Between May 2021 and June 2022, 36 patients with symptomatic fibroids or adenomyosis underwent UAE with MAC. Follow-up evaluations consisted of clinical symptoms, degree of satisfaction with MAC in UAE, and complications. Result(s): MAC in UAE was successfully performed in all patients. UAE significantly reduced patients' complaints such as bleeding and pain: the scores for bleeding and pain were significantly reduced after 3 months of UAE compared with those before UAE, indicating the effectiveness of UAE. The mean score of satisfaction with MAC in UAE was 4.3 points, meaning that 94.4% of women were satisfied or very satisfied. No major complications were observed. Conclusion(s): MAC in UAE for symptomatic uterine fibroids or adenomyosis can be emotionally effective and safe for patients who are anxious about the procedure.Copyright © 2023 The Author(s).

O'Hara, R., et al. (2019). "Self-management in condition-specific health: a systematic review of the evidence among women diagnosed with endometriosis." BMC Women's Health 19(1): 80.
	Background: Endometriosis is a chronic condition, requiring long-term care as there is no cure. Self-management is the active participation of a person in managing their chronic condition and has been associated with improved knowledge, self-efficacy, performance of self-management tasks and some aspects of health status in interventions for other chronic diseases. The aim was to review the available evidence about the impact of self-management on condition-specific health among women with endometriosis.; Methods: The Medline, PsycINFO, CinahlPlus, Web of Science and Scopus databases were searched and PRISMA guidelines were followed. Search terms were entered both as keywords and mapped to individual database subject headings. Inclusion criteria were: papers that reported investigations of any approach to self-management; among women (at least 18 years) diagnosed with endometriosis and published in English in a peer-reviewed journal. All study designs using quantitative or qualitative methods were eligible for inclusion. Two reviewers independently examined the quality of studies using standard criteria. The systematic review was registered with Prospero (CRD42016042028).; Results: A total of 1164 records were identified (after duplicates were removed), and 27 papers, reporting 19 studies met inclusion criteria. Two papers reported findings from RCTs of complementary therapies, seven reported survey data and 18 qualitative studies. No study had investigated all elements of self-management. Women with endometriosis utilise a range of self-care activities and complementary therapies to assist them to manage their symptoms. Women reported both positive and negative experiences with health care providers.; Conclusions: There is some evidence that self-care activities, complementary therapies and positive patient-healthcare provider relationships are important components of self-management for endometriosis. Self-management among women with endometriosis is an emerging field of research and no investigations of all elements of self-management, informed by a comprehensive definition and theoretical framework are available. Health and wellbeing outcomes and barriers and facilitators to self-management for women with endometriosis require further investigation.

Ohba, K., et al. (2021). "Efficacy of propiverine hydrochloride for urinary incontinence after robot-assisted or laparoscopic radical prostatectomy." Canadian journal of urology 28(3): 10706‐10712.
	INTRODUCTION: To clarify the efficacy and safety of propiverine hydrochloride for incontinence after robot‐assisted laparoscopic prostatectomy (RALP)/laparoscopic radical prostatectomy (LRP), along with changes in the urethral pressure profile (UPP) and quality of life in patients treated with propiverine hydrochloride. MATERIALS AND METHODS: In this randomized, comparative study, 104 patients who were aware of urinary incontinence after RALP or LRP were assigned to receive propiverine hydrochloride (treatment group) or not (controls). Pad test results, International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF) scores, and UPP results [including maximum urethral closure pressure (MUCP) and functional urethral length (FUL)], were recorded immediately and at 6 months postoperatively. RESULTS: No serious intraoperative complications or adverse events were caused by propiverine hydrochloride. The pad‐test negative rate was significantly greater in the treatment group than in controls (89.1% vs. 73.2%, p = 0.044). Changes in ICIQ‐SF scores and MUCP were significantly greater in the treatment group than in controls [‐6.5 vs. ‐4.5 points (p = 0.021), and +49.5 vs. +28.7 mmHg (p = 0.038), respectively]. FUL change did not significantly differ between groups [+4.5 vs. +3.8 mm (p = 0.091)]. In univariate logistic regression analyses, body mass index (BMI), MUCP, and treatment with propiverine hydrochloride were significantly associated with continence status. In multivariate analyses, BMI and MUCP were independently associated with continence status [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.047‐1.530 (p = 0.015), and OR, 0.986; 95% CI, 0.973‐0.999 (p = 0.042), respectively]. CONCLUSIONS: Treatment with propiverine hydrochloride alleviated urinary incontinence while improving patient symptoms and quality of life after RALP or LRP.

Okafor, I. A., et al. (2023). "Herbal treatment options for female fertility disorders: a systematic review of clinical trials." Physiology and Pharmacology (Iran) 27(4): 357-386.
	Introduction: Herbal medicine has been used as tea, ointment, capsules, syrup, whole herbs, and tablets to treat fertility disorders. The herbs and their treatment use in different localities vary, and the effectiveness of herbal treatment for routine treatment of diseases is still a debated issue to date. This study is a 20-year review of the herbal medicines treatment options for female fertility disorders to provide an updated publication of herbal treatments for female infertility and their associated outcomes, informing further research or translation. Method(s): PubMed, Google Scholar, Web of Science, Science Direct, and Cochrane databases were searched for clinical trials using Medical Subject Headings (MeSH) terms and related keywords, which retrieved 336 studies. All cross-sectional studies, reviews, and controlled trials utilizing phytotherapy on study participants without evidence of female infertility were excluded. Only 23 studies published in the English Language between January 2002 and August 2021 were included in the evidence synthesis after article screening. Result(s): Several herbal treatments in women cause a significant reduction in the symptoms of primary dysmenorrhea, PCOS, endometriosis, luteal phase defect, and vulvovaginal candidiasis, with substantial improvements in pregnancy and live birth rates. The herbal drugs identified from available studies were formulations - tablets or creams-with specified doses and administered orally or intravaginally. Conclusion(s): Evidence exists that herbal treatments effectively treat female fertility disorders. However, they have not fully established the extent of safety, side effects, and pharmacological mechanisms of the therapeutic effects attributed to these herbal treatments.Copyright © 2023, Iranian Society of Physiology and Pharmacology. All rights reserved.

Okamuro, K., et al. (2023). "A PRACTICE-BASED INTERVENTION TO IMPROVE THE CARE OF WOMEN WITH URINARY INCONTINENCE: PROTOCOL FOR A CLUSTER RANDOMIZED CONTROLLED TRIAL." Journal of urology 209(Supplement 4): e758-e759.
	INTRODUCTION AND OBJECTIVE: Urinary incontinence (UI) presents an immense human and financial burden to American women. The impact of this condition will only continue to rise as the population ages, yet primary care for UI has been inadequate to date. The primary objective of this study is to improve the quality of UI care provided to women through a controlled practice-based intervention for primary care providers. Secondary objectives include evaluating the effect of the intervention on referral rates to specialists, improving patient-centered outcomes, reducing disparities in care, and disseminating findings to a diverse population of patients and providers. METHOD(S): Sixty offices across 4 Southern California medical institutions will be randomized to receive a four-pronged practice-based incontinence intervention vs. routine care. The intervention involves academic detailing (physician education and individual performance feedback), clinical decision support (note templates, order sets, and best practice advisory), co-management with a dedicated advanced practice provider, and implementation of an electronic consult referral service in which inappropriate referrals are returned with recommendations. RESULT(S): The quality of care, as measured by compliance with a set of 12 quality indicators, will be measured across the arms after implementation of the intervention. Patient-reported outcomes and utilization of specialists will also be compared. After the initial intervention phase, there will be a validation phase in which the control group will cross over and receive the intervention. CONCLUSION(S): The potential reach of this pragmatic practice- based trial in Southern California is vastdwith 900 patients, 225 providers, 60 offices, and 4 medical institutions directly impacted. The results of the study will also contribute to the translation of patientcentered outcomes research into clinical practice, impacting women locally and nationally. (Figure Presented).

Okeke, O., et al. (2021). "Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial." BJOG : an international journal of obstetrics and gynaecology 128(9): 1534-1545.
	Objective: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage.; Design: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS).; Setting: Twenty-eight UK NHS early pregnancy units.; Sample: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage.; Methods: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets.; Main Outcome Measures: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs).; Results: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management.; Conclusions: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage.; Tweetable Abstract: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages. (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Okonogi, N., et al. (2022). "An Asian multi-national, multi-institutional, retrospective study on image-guided brachytherapy in cervical adenocarcinoma and adenosquamous carcinoma." Journal of Contemporary Brachytherapy 14(4): 311-320.
	Purpose: There are limited reports on outcomes of three-dimensional image-guided brachytherapy (3D-IGBT) for cervical adenocarcinoma in Asia. In a multi-institutional retrospective study, we assessed the clinical outcomes of three-dimensional image-guided brachytherapy for cervical adenocarcinoma or adenosquamous carcinoma (CA/CAC) in Asian countries.; Material and Methods: Patients who had undergone definitive radiation therapy/concurrent chemoradiotherapy for untreated cervical cancer between 2000 and 2016 were registered. Those who had undergone 3D-IGBT for histologically proven CA/CAC were included. Data on patients' characteristics and treatment were collected, including tumor reduction rate (defined as a percentage of reduction in tumor size before brachytherapy compared with that at diagnosis) and high-risk clinical target volume D 90 . Overall survival (OS), local control (LC), and progression-free survival (PFS) rates were calculated using Kaplan-Meier method. Late toxicities were assessed using common terminology criteria for adverse events version 4.0.; Results: Anonymized data of 498 patients were collected. Of the 498 patients, 36 patients met inclusion criteria. The median follow-up period was 39 months. The 3-year OS, LC, and PFS rates were 68.4%, 68.5%, and 44.4%, respectively. After treatment, five patients had tumor re-growth without complete disappearance of the tumor. Two patients developed grade 3 vaginal toxicity or grade 4 rectal toxicity; none developed other severe late toxicities. A tumor reduction rate of > 26.3% was the only significant factor in multivariate analyses, and was associated with significantly better OS ( p = 0.018), LC ( p = 0.022), and PFS ( p = 0.013). There were no significant trends in local control or dose to high-risk clinical target volume D 90 .; Conclusions: LC rate of CA/CAC was insufficient despite 3D-IGBT. Meanwhile, tumor reduction rate was associated with LC, OS, and PFS rates. Therefore, CA/CAC may require a different treatment strategy than that applied in cervical squamous cell carcinoma.; Competing Interests: Dr Okonogi reports grants and other (investigational drug supply) from AstraZeneca clinical trial, outside the submitted work. Dr Igaki reports grants and personal fees from HekaBio, grants from CICS, grants from Elekta KK, personal fees from AstraZeneca, personal fees from Itochu, personal fees from HIMEDIC, and personal fees from Varian, outside the submitted work. Dr Itami reports grants from Elekta KK, grants and personal fees from Itochu, personal fees from ViewRay, personal fees from Palette Science, personal fees from Alpha-TAU, and personal fees from HekaBio, outside the submitted work. This study received no financial support from any company; thus, there are no conflicts of interests to declare. (Copyright © 2022 Termedia.)

Okonogi, N., et al. (2023). "A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results." International Journal of Molecular Sciences 24(13).
	We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m 2 . Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

Okonogi, N., et al. (2022). "Phase Ib study of durvalumab (MEDI4736) in combination with carbon-ion radiotherapy and weekly cisplatin for patients with locally advanced cervical cancer (DECISION study): study protocol for a prospective open-label single-arm study." BMJ Open 12(3): e056424.
	Introduction: Concurrent chemoradiotherapy is considered the standard treatment strategy for locally advanced cervical cancer. Most recent reports indicate that patients with bulky tumours or adenocarcinoma subtypes have poorer local control. Carbon-ion radiotherapy (CIRT) with the concurrent use of chemotherapy has shown promising results in such cases of difficult-to-treat uterine cervical cancer. Programmed death-ligand 1 (PD-L1) upregulation was observed in tumour tissue samples from patients who had undergone CIRT. Thus, a combination of CIRT and anti-PD-L1 antibody may suppress metastasis by activating antitumour immune response, in addition to exhibiting strong local effects.; Objective: We will assess the safety and tolerability (primary endpoint) of the concomitant use of durvalumab, an anti-PD-L1 antibody, with CIRT and weekly cisplatin for locally advanced cervical cancer.; Methods and Analysis: This study is a non-randomised, open-label, prospective phase 1b study. Up to 10 patients with histologically proven uterine cervical cancer at stage IIB, IIIA, IIIB, IIIC1 or IVA as per International Federation of Gynecology and Obstetrics (2018) staging will be enrolled. All patients will receive CIRT of 74.4 Gy relative biological effectiveness in 20 fractions over 5 weeks (four fractions per week). Weekly cisplatin at a dose of 40 mg/m 2 will be administrated up to five times. Durvalumab at a dose of 1500 mg/body will be administrated at weeks 2 and 6. Safety and tolerability will be evaluated based on the frequency of dose-limiting toxicities until 92 days after CIRT starts. Patients will be followed-up strictly as per the scheduled protocol for 1 year after CIRT initiation.; Ethics and Dissemination: The Human Research Ethics Committees of QST Hospital (#C21-002) and Chiba University (#2021006) have approved this study protocol. The findings will be published in peer-reviewed journals and presented at scientific conferences.; Trial Registration Number: Japan Registry of Clinical Trials (jRCT2031210083), registered on 12 May 2021.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Oktay, K. H. and L. Marin (2024). "Comparison of orthotopic and heterotopic autologous ovarian tissue transplantation outcomes." Fertility and Sterility 121(1): 72-79.
	Objective: To compare the outcomes of orthotopic and heterotopic ovarian tissue transplantation (OTT) techniques. Design(s): Mixed prospective-retrospective cohort study. Setting(s): Academic hospital. Patient(s): A total of 14 recipients of autologous OTT. Intervention(s): Of the 14 women, 12 who received orthotopic (n = 6) or heterotopic (n = 6) transplants met the inclusion criteria. All orthotopic transplants and one heterotopic ovarian tissue transplant were performed laparoscopically. Although 5 of the 6 remaining heterotopic transplants were performed subcutaneously under local anesthesia or intravenous sedation, one was performed with robotic assistance. With the exception of one recipient who solely desired restoration of endocrine function, all underwent oocyte retrieval either to cryopreserve oocytes and embryos before the graft function ceased or because they could not otherwise conceive (hysterectomy, radiation damage, and heterotopic transplant). Main Outcome Measure(s): Primary outcome measures were graft function and longevity, and the number of embryos generated per retrieval. Result(s): The mean age at ovarian tissue harvesting and transplantation was lower in patients with orthotopic vs. heterotopic transplants, although the proportion of transplanted ovarian cortex was lower in heterotopic transplant cases. All grafts restored ovarian endocrine function. Fertilization rates, the number of embryos generated per retrieval, and the mean number of nonarrested embryos were significantly lower in heterotopic OTT. However, time to function and graft longevity were similar between the groups. Although 4 of the 6 women conceived and delivered 7 children among orthotopic ovarian tissue recipients, one recipient had 3 spontaneous live births after heterotopic OTT, presumably because of the induction of function in the remaining menopausal ovary. Conclusion(s): It appears that orthotopic OTT results in higher gamete and embryo quality. However, the endocrine function restoration rate and longevity are similar between the 2 approaches. When feasible, orthotopic OTT should be preferred for those who intend to conceive, although a less invasive heterotopic OTT can be performed for those who primarily desire ovarian endocrine function.Copyright © 2023 American Society for Reproductive Medicine

Okubo, T., et al. (2023). "Resection of Cervical Dumbbell-Shaped Schwannoma Using Posterior Unilateral Approach: Impact on Postoperative Cervical Function and Clinical Outcomes." Global Spine Journal.
	Study Design: A retrospective comparative study Objectives: This study aimed to evaluate the radiographical changes in cervical sagittal alignment (CSA) and clinical outcomes after tumor resection using a posterior unilateral approach without spinal fixation for patients with cervical dumbbell-shaped schwannoma (DS). Method(s): Seventy-three patients with DS who were followed up for at least 2 years were included. The Eden classification was used to designate the types of DS. The CSA and range of motion (ROM) were analyzed using radiographs. The clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) score and JOA cervical myelopathy questionnaire. Result(s): The CSA in the neutral, flexion, and extension position and cervical ROM were not significantly reduced in the follow-up period. The JOA scores showed significant improvement after surgery. The postoperative radiographic parameters and clinical outcomes of Eden type II or III DS, which needed facetectomy for the resection, did not show any statistically significant difference compared with those of Eden type I tumor, which was resected without facetectomy. Fifty-two cases (71.2%) achieved gross total resection, whereas 21 cases (28.8%) remained in partial resection (PR). One case underwent reoperation due to the regrowth of the remnant tumor whose margin was at the entrance of the intervertebral foramen. Conclusion(s): Tumor resection using the posterior unilateral approach preserved CSA and resulted in favorable clinical outcomes in patients with DS. When the resection ends in PR, the proximal margin of the remnant tumor should be located distally away from the entrance of the foramen to prevent regrowth.Copyright © The Author(s) 2023.

Okugawa, K., et al. (2022). "Evaluation of Clinical Significance of Lymphovascular Space Invasion in Stage IA Endometrial Cancer." Oncology 100(4): 195-202.
	Introduction: The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer.; Methods: Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports.; Results: Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and 4 patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and -negative groups (p = 0.07 and p = 0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (p = 0.11 and p = 0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (p = 0.92 and p = 0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively.; Conclusion: LVSI was not a prognostic factor of not only stage IA endometrial cancer but also stage IA low-grade cancer. (© 2021 S. Karger AG, Basel.)

Okui, N., et al. (2022). "Comparison of urethral sling surgery and non-ablative vaginal Erbium:YAG laser treatment in 327 patients with stress urinary incontinence: a case-matching analysis." Lasers in Medical Science 37(1): 655-663.
	Stress urinary incontinence (SUI) occurs when abdominal pressure, such as from coughing or sneezing, causes urine leakage. We retrospectively compared tension-free vaginal tape (TVT) and non-ablative vaginal Erbium:YAG laser treatment (VEL) by propensity score (PS) analysis in women with SUI. No PS analysis studies have investigated urethral sling surgery using polypropylene TVT and VEL for SUI. Data from patients aged 35-50 years who were treated for SUI and registered at several institutions were selected. Patients with medical records covering 1 year for the 1-h pad test, who completed the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the Overactive Bladder Symptom Score (OABSS), were included. We analyzed 102, 113, and 112 patients in the TVT, VEL, and control groups, respectively. Compared with the control group, the TVT and VEL groups exhibited significant improvement in the 1-h pad test and ICIQ-SF. In the PS analysis, the TVT and VEL groups similarly improved in the 1-h pad test and ICIQ-SF. As for the OABSS, the VEL group showed significantly greater improvement than the TVT group. In the odds ratio analysis for the 1-h pad test, no differences in any of the parameters were observed between TVT and VEL. VEL may be considered an alternative to TVT for SUI treatment.Copyright © 2021, The Author(s).

Okunade, K., et al. (2022). "COMPARATIVE ASSESSMENT OF PATTERNS OF RECURRENCE BETWEEN PRIMARY AND INTERVAL DEBULKING SURGERY IN ADVANCED EPITHELIAL OVARIAN CANCER: ANALYSIS FROM A TERTIARY REFERRAL CENTRE." International Journal of Gynecological Cancer 32(Supplement 3): A169.
	Objectives This study assessed the differences in the pattern and timing of recurrence in women with advanced epithelial ovarian cancer (EOC) who had primary debulking surgery (PDS) followed by chemotherapy or interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT). Methods Retrospective data on the sociodemographic and clinical characteristics and laboratory parameters together with the recurrence status after a 3-year follow-up of 126 women with advanced EOC who had undergone standard treatment between January 2008 and December 2017 were collected and analysed. Results There were 46 (68.7%) recurrences in the IDS group compared to 37 (62.7%) in the PDS group (P=0.88). The Kaplan-Meier curve comparing the progression-free survival (PFS) between PDS and IDS in women with advanced EOC showed no statistically significant difference (P=0.38). There was also no statistically significant association between type of surgical treatment and PFS after adjustments for covariates such as age and pre-existing medical morbidity in the multivariate analysis (HR=1.46, 95%CI: 0.90-2.37, P=0.12). Conclusions We found no conclusive evidence to suggest that IDS between cycles of chemotherapy compared with conventional treatment using PDS followed by adjuvant chemotherapy (ACT) improved the PFS of women with advanced EOC. We, therefore, suggest a need to further evaluate the potential benefit of an individualised treatment selection rather than a blind extrapolation of all women with advanced EOC to NACT and IDS.

Okyay Recep, E., et al. (2022). "The effect of oral contraceptive use on sympatic nerve activity in patients with polycystic ovary syndrome." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(7): 592-597.
	Objective: High sympathetic nerve activity, is thought to be a cardiovascular risk factor, has been shown to correlate with circulating high testosterone levels. However its role on the pathophysiology of the polycystic ovarian syndrome has not been clearly established. The aim of our study is to compare the sympathetic nerve activity between polycystic ovarian syndrome and control group and to determine whether the use of oral contraceptives for contraception has any effect on this activity.; Materials and Methods: Our study has designed as a prospective, case-control study including patients diagnosed with polycystic ovarian syndrome. Antropometric measurements were calculated, hormone levels were measured and sympathetic skin response and heart rate variability measurements were performed in the laboratory to assess sympathetic activity before starting oral contraceptive pill therapy and at the end of 1 month follow up.; Results: In the baseline condition LH/FSH ratio, LH, DHEAS, and total testosterone levels were significantly higher in women with PCOS. After 1 month of treatment, reductions in Ferriman-Gallwey score, ovarian volumes, number of follicles, LH/FSH ratio, LH, and androgen hormone levels were statistically significant. The mean values of sympathetic skin response amplitude and R-R analysis-Valsalva test were higher in PCOS group as compared to the control group. However, these differences were not statistically significant. Similarly, no statistically significant difference in SSR latency and R-R analysis-standup test were demonstrated between PCOS and control groups.; Conclusion: In conclusion, our study supports the increased sympatovagal activity in patients with polycystic ovarian syndrome.

Olabiyi, A. A., et al. (2021). "Role of purinergic system and vitamin D in the anti-cancer immune response." Life Sciences 287: 120110.
	For several years, scientists have recognized that vitamin D plays an important role in mineral and bone homeostasis. It was mostly used to treat osteoporosis and rickets in the past decades. Vitamin D has also been discovered to be modulator of the immune system and may play a role in a variety of diseases, including autoimmune diseases, in recent years. Vitamin D interaction with the vitamin D receptor (VDR), which has transcriptional imparts and is displayed on a variety of cell types, including those of the immune system, appears to be accountable for the immune-modulating effects. The action of tumor cells and vitamin D were the first to be investigated, but the spotlight is now on immunologic and purinergic systems. We conducted a systematic search in Pub Med as well as Google scholar for studies written in English. Vitamin D, cancer, purinergic signaling, and immune response were among the search words. Vitamin D has the potential to be a useful coadjuvant in cancer therapy and the purinergic system may be a potential treatment target to cancer therapy, according to our findings.Copyright © 2021 Elsevier Inc.

Olcha, P., et al. (2022). "Antioxidative, Anti-Inflammatory, Anti-Obesogenic, and Antidiabetic Properties of Tea Polyphenols-The Positive Impact of Regular Tea Consumption as an Element of Prophylaxis and Pharmacotherapy Support in Endometrial Cancer." International Journal of Molecular Sciences 23(12).
	Endometrial cancer (EC) is second only to cervical carcinoma among the most commonly diagnosed malignant tumours of the female reproductive system. The available literature provides evidence for the involvement of 32 genes in the hereditary incidence of EC. The physiological markers of EC and coexisting diet-dependent maladies include antioxidative system disorders but also progressing inflammation; hence, the main forms of prophylaxis and pharmacotherapy ought to include a diet rich in substances aiding the organism's response to this type of disorder, with a particular focus on ones suitable for lifelong consumption. Tea polyphenols satisfy those requirements due to their proven antioxidative, anti-inflammatory, anti-obesogenic, and antidiabetic properties. Practitioners ought to consider promoting tea consumption among individuals genetically predisposed for EC, particularly given its low cost, accessibility, confirmed health benefits, and above all, suitability for long-term consumption regardless of the patient's age. The aim of this paper is to analyse the potential usability of tea as an element of prophylaxis and pharmacotherapy support in EC patients. The analysis is based on information available from worldwide literature published in the last 15 years.

O'Leary, M. F., et al. (2021). "Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus lateralis Myosin Regulatory Light Chain Phosphorylation but Does Not Alter Markers of Bone Turnover." Nutrients 13(12).
	Shatavari has long been used as an Ayurvedic herb for women’s health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor. Postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis. In a randomised double‐blind trial, 20 postmenopausal women (68.5 ± 6 years) in‐gested either placebo (N = 10) or shatavari (N = 10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented as difference scores (Week 6—baseline, median ± interquartile range). Handgrip (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo −0.4 ± 1.3 kg; p = 0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo −0.08 ± 0.5 a.u., shatavari +0.3 ± 1 arbitrary units (a.u.); p = 0.03). Shatavari increased the phosphorylation of Aktser473 (Aktser473 (placebo −0.6 ± 0.6 a.u., shatavari +0.2 ± 1.3 a.u; p = 0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, β‐CTX) and stimulation of human osteoblasts with pooled sera (N = 8 per condition) from placebo and shatavari supplemen‐tation conditions did not alter cytokine or metabolic markers of osteoblast activity. Shatavari may improve muscle function and contractility via myosin conformational change and further investi‐gation of its utility in conserving and enhancing musculoskeletal function, in larger and more di‐verse cohorts, is warranted.

Olejek, A., et al. (2024). "Linzagolix provides rapid, significant reduction of heavy menstrual bleeding in women with uterine fibroids." European Journal of Obstetrics and Gynecology and Reproductive Biology 293: 131.
	Introduction and aims of the study: Linzagolix (LGX), a new oral gonadotropin-releasing hormone (GnRH) antagonist, was assessed in women with heavy menstrual bleeding (HMB; > 80 mL menstrual blood loss [MBL]/cycle) due to uterine fibroids in two placebo-controlled Phase 3 trials, PRIMROSE 1 and 2. Method(s): 1012 women were treated with LGX100mg, LGX100mg plus add-back-therapy (ABT; estradiol E2:1 mg/norethisterone acetate NETA:0.5 mg), LGX200mg or LGX200 mg+ABT for up to 52 weeks. The primary efficacy endpoint was a reduction in alkaline-hematin-documented MBL to <= 80mL and reduction of >=50% at 24 weeks. Time to reduced MBL was assessed as secondary endpoint. Results and/or discussion: The mean baseline MBL was 208mL. There was a rapid reduction in MBL within days of initiating therapy with significant reductions at 24 weeks in all active groups. The responder rate on LGX100mg, LGX100 mg+ABT, LGX200 mg or LGX200 mg + ABT was 57%, 72%, 75% and 85%, respectively compared to 32% on placebo (p < 0.001). Amenorrhea was achieved in 36%, 52%, 65% and 69%, respectively compared to 17% on placebo (p < 0.001). The reduction in MBL was maintained over time until 52 weeks. The time to reduced MBL was significantly shorter in all active treatment groups compared to placebo, with median Kaplan-Meyer estimates (estimating the length of time until occurrence of the event in 50% of subjects) of 135 days (d), 12d, 3d and 3d for the respective active groups (p < 0.001). Linzagolix was well tolerated during this time. Conclusion(s): Once daily doses of new oral GnRH antagonist - linzagolix 100mg and 200mg with or without ABT provide fast and efficient bleeding control in women with HMB due to uterine fibroids. Improvements are maintained with prolongation of treatment. This particularly rapid onset of action is an appreciated treatment feature that might be importance in selected patients.Copyright © 2023

Oliveira Marco Aurelio, P., et al. (2023). "Robotic Surgery for Bladder Endometriosis: A Systematic Review and Approach." Journal of Clinical Medicine 12(16).
	Introduction: Women with bladder endometriosis often present with more advanced stages of endometriosis. Robotic surgery has emerged as a promising approach to the management of bladder endometriosis. This systematic review aims to analyze the current literature on robotic surgery for bladder endometriosis and describe our systematic approach to surgical treatment.; Methods: This review followed the PRISMA guidelines, which ensured a comprehensive and transparent approach to selecting and evaluating relevant studies. We conducted a thorough literature search to identify studies that investigated the use of robotic surgery for bladder endometriosis. Relevant databases were searched, and inclusion and exclusion criteria were applied to select eligible studies. Data extraction and analysis were performed to assess the outcomes and effectiveness of robotic surgery for the treatment of bladder endometriosis.; Results: We did not find any randomized clinical trials with the use of robotics in the treatment of bladder endometriosis. We found only two retrospective studies comparing robotic surgery with laparoscopy, and another retrospective study comparing robotic surgery, laparoscopy, and laparotomy in the treatment of bladder endometriosis. All the other 12 studies were solely case reports. Despite the lack of robust evidence in the literature, the studies demonstrated that robotic surgery is feasible and is associated with reduced postoperative pain, shorter hospital stays, and faster recovery.; Conclusions: The utilization of robotic technology is a promising option for the surgical management of bladder endometriosis. We advocate a surgical systematic approach for the robotic treatment of bladder endometriosis. Robotic technology, with its 3D vision, instrumental degrees of freedom, and precision, particularly in suturing, may provide potential benefits over traditional laparoscopy.

Oliveira, M. C., et al. (2021). "Evaluation of satisfaction of pelvic floor muscle training isolated and associated with tibial nerve stimulation in women with mixed urinary incontinence: A randomized, single-blinded clinical trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 265: 60-65.
	OBJECTIVES: To compare the satisfaction degree and pelvic floor manometry after pelvic floor muscle training isolated and associated with tibial nerve stimulation in women with mixed urinary incontinence (MUI). STUDY DESIGN: A randomized, single-blinded clinical trial was conducted. 24 women diagnosed with MUI were equally divided into two groups: pelvic floor muscle training isolated and associated to transcutaneous tibial nerve stimulation (TTNS). The study occurred in four stages: 1) evaluation: general information, pelvic floor manometry, the International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF) and International Consultation on Incontinence Questionnaire - Overactive Bladder (OAB) application; 2) intervention: carried out over 2 months twice a week; 3) post-intervention evaluation: vaginal manometry, reapplication of the questionnaires and the Patient Global Impression (PGI) application at the end of the 2-month intervention; and, 4) follow-up: evaluation after 1 month of the end of the intervention. The primary outcome was the ICIQ-UI-SF and the secondary outcomes were ICIQ-OAB, vaginal manometry, and PGI. The repeated measures ANOVA was used to assess the time-to-group interaction by assigning a significance level of 5%. RESULTS: There was no interaction between time and group for ICIQ-UI-SF (p = 0.17) and manometry (p = 0.56). There was interaction for ICIQ-OAB (p < 0.01). PGI was reported as "much better" with 41.67% in the PFMTG + TTNS and 16.67% in the PFMTG after the intervention (p = 0.04). CONCLUSIONS: The results showed weak evidence that TTNS, in combination with PFMT, may be an intervention that can be used to treat MUI. The satisfaction degree was better with associated intervention.

Oliveira, R., et al. (2022). "Comparing Two- and Three-dimensional Antral Follicle Count in Patients with Endometriosis." Journal of Medical Ultrasound 30(4): 282-286.
	Background: The purpose of the study was to compare three-dimensional (3D) ultrasound semiautomatic antral follicle count (AFC) with two-dimensional (2D) ultrasound real-time AFC to evaluate patients with deep endometriosis and/or endometrioma submitted to ovarian stimulation (OS). Method(s): This was a retrospective cohort study assessing all women with documented diagnosis of deep endometriosis who underwent OS for assisted reproduction treatment. The primary outcome was the difference between AFC by semiautomatic 3D follicle count using 3D volume datasets and 2D ultrasound count with the number of oocytes retrieved at the end of the cycle. The 3D ultrasound AFC was obtained using sonography-based automated volume count (SonoAVC), and the 2D ultrasound AFC data was collected from the electronic medical record. Result(s): Total of 36 women had deep endometriosis documented by magnetic resonance imaging, laparoscopy, or ultrasonography and 3D ovarian volume datasets stored from their first exam. The differences between the 2D and 3D AFC and the number of oocytes retrieved at the end of the stimulation were compared, showing no significant statistical difference between both methods (P = 0.59). Correlations were similar using both methods when compared to the number of oocytes retrieved (2D [r = 0.83, confidence interval (CI) = 0.68-0.9, P < 0.001]); (3D [r = 0.81, CI = 0.46-0.83, P < 0.001]). Conclusion(s): 3D semiautomatic AFC can be used to access the ovarian reserve in patients with endometriosis.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Olivia, H., et al. (2021). "Systematic Review of Therapies for Female Pelvic Floor Myalgia."
	
Olthof, E. P., et al. (2022). "RADICAL HYSTERECTOMY IS NOT SUPERIOR TO CHEMORADIATION IN EARLY STAGE CERVICAL CANCER WITH SUSPICIOUS LYMPH NODES: A PROPENSITY SCORE ANALYSIS." International Journal of Gynecological Cancer 32(Supplement 2): A61-A62.
	Introduction/Background This retrospective cohort study aims to compare radical hysterectomy with primary chemoradiation regarding survival and toxicity (<=6 months) in women with early-stage cervical cancer and suspicious lymph nodes on pretreatment imaging. Methodology Women diagnosed between 2009-2017 with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IA-IIA, suspicious/inconclusive pelvic and/ or para-aortic nodes on radiological judgement by pretreatment imaging (i.e. computed tomography, magnetic resonance imaging, and/or positron emission tomography), and treated by radical hysterectomy with lymphadenectomy, or chemoradiation were selected from the Netherlands Cancer Registry. Propensity score stratification for age, FIGO, tumour morphology and size, suspicious node short-axis, location, and status was applied to control for heterogeneity between both treatment groups. Overall and recurrence-free survival were compared by Cox regression analyses, toxicity (Clavien-Dindo grade >=2 and Common Terminology Criteria for Adverse Events >=3) by logistic regression. Results Of 319 patients included, 131 (41%) were treated by radical hysterectomy and 188 (59%) by chemoradiation. The pathological nodal status was known in 100% and 33% of the patients, of whom 43% (56/131) and 89% (54/61) had metastases, respectively. Radical hysterectomy was followed by (chemo)radiation in 54%. After balancing for confounding factors, radical hysterectomy yielded an almost similar overall (HR 0.91; CI 0.44-1.90) and recurrence-free (HR 1.18; CI 0.58-2.42) survival compared to chemoradiation (figure 1). However, radical hysterectomy was associated with more toxicity (n=44; 34%) compared to chemoradiation (n=37; 20%; p=0.006), also in adjusted analysis (OR 2.35; CI 1.18-4.68) and mainly caused by surgery-related complications (i.e. infection, bladder dysfunction, and blood transfusion) in 34 patients (26%). Conclusion After balancing confounding factors, overall and recurrence-free survival were not significantly different between radical hysterectomy and chemoradiation. Radical hysterectomy was associated with more toxicity compared to chemoradiation, mainly surgery-related and short-term. (Figure Presented).

Olthof Ester, P., et al. (2022). "Treatment of bulky lymph nodes in locally advanced cervical cancer: boosting versus debulking." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(7): 861-868.
	Objective: Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment.; Methods: Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis.; Results: Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83).; Conclusions: This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.)

Oluloro, A., et al. (2024). "Study Protocol for the Social Interventions for Support During Treatment for Endometrial Cancer and Recurrence (SISTER) study: a community engaged national randomized trial." Journal of comparative effectiveness research 13(3): e230159.
	Aim: Social isolation in cancer patients is correlated with prognosis and is a potential mediator of treatment completion. Black women with endometrial cancer (EC) are at increased risk for social isolation when compared with White patients. We developed the Social Interventions for Support during Treatment for Endometrial Cancer and Recurrence (SISTER) study to compare and evaluate interventions to address social isolation among Black women with high-risk EC in USA. The primary objective of the SISTER study is to determine whether virtual support interventions improve treatment completion compared with Enhanced Usual Care. Secondary objectives include comparing effectiveness virtual evidence-based interventions and evaluating barriers and facilitators to social support delivery. Patients & methods: This is a multi-site prospective, open-label, community-engaged randomized controlled trial, consisting of three intervention arms: enhanced usual care, facilitated support group and one-to-one peer support. Primary outcome will be measured using relative dose. Qualitative semi-structured interviews will be conducted with a subset of participants to contextualize the relative degree or lack thereof of social isolation, over time. Data analysis: Primary analysis will be based on an intent-to-treat analysis. Multivariable analysis will be performed to determine the effect of the intervention on the primary and secondary outcomes of interest, relative dose and social isolation score. Semi-structured interviews will be qualitatively analyzed using inductive and deductive approaches of content analysis. Discussion/conclusion: Endometrial cancer mortality disproportionately affects Black women, and social isolation contributes to this disparity. The SISTER study aims to identify whether and to what extent differing social support vehicles improve key outcomes for Black women in the United States with high-risk EC. Clinical Trial Registration: NCT04930159 (ClinicalTrials.gov).

Oluseyi, A., et al. (2022). "The cost of antimicrobial resistance in curable sexually transmitted infections : a systematic review of economic evaluations and cost studies."
	
O'Malley, D., et al. (2022). "Pembrolizumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial cancer: Long-term follow-up results from KEYNOTE-158." Annals of Oncology 33(Supplement 7): S796-S797.
	Background: Pembrolizumab (pembro) previously demonstrated robust and durable antitumor activity in patients with MSI-H/dMMR advanced endometrial cancer in the open-label, multicohort, phase 2 KEYNOTE-158 study (NCT02628067). Here we report updated efficacy and safety outcomes with a substantially longer follow-up in the patients enrolled. Method(s): This analysis included those patients with previously treated, MSI-H/dMMR advanced endometrial cancer enrolled in cohorts D (advanced endometrial cancer of any MSI/MMR status) and K (any MSI-H/dMMR advanced solid tumor, except colorectal) of KEYNOTE-158. MSI-H/dMMR status was determined retrospectively by PCR at a central lab in cohort D and prospectively by PCR and/or IHC at a local lab in cohort K. Patients received pembro 200 mg Q3W for up to 35 cycles. Primary endpoint was ORR per RECIST v1.1 by independent central radiologic review. Secondary endpoints included DOR, PFS, OS, and safety. Result(s): 94 patients with previously treated MSI-H/dMMR advanced endometrial cancer were included in this analysis. Median time from first dose to data cutoff (Jan 12, 2022) was 54.5 (range, 14.7-71.4) mo. Efficacy results are shown in the Table. ORR was 50% (95% CI, 39.5%-60.5%); responses were seen across all prior treatment lines. 4-y DOR rate was 66% by K-M estimate. Median (95% CI) PFS and OS were 13.1 (4.3-25.7) mo and 65.4 (29.5-NR) mo; 4-y PFS and OS rates were 37% and 59%, respectively. Treatment-related AEs occurred in 71 patients (76%); 13 patients (14%) had grade 3-4 treatment-related AEs (no grade 5). [Formula presented] Conclusion(s): These updated results reconfirm the robust and durable antitumor activity of pembro and show encouraging survival outcomes in patients with advanced endometrial carcinoma that is MSI-H/dMMR, who have PD following prior systemic therapy and are not candidates for curative surgery or radiation, supporting the use of pembro in this setting. Clinical trial identification: NCT02628067. Editorial acknowledgement: Medical writing support was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Legal entity responsible for the study: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Funding(s): Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Disclosure: D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, BBI, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance Biotherapeutics, Inc, Myriad Genetics, Eisai, Agenus, Tarveda, Merck & Co., Inc., Rahway, NJ, USA, SeaGen, Novartis,; Financial Interests, Institutional, Research Grant: AstraZeneca, Tesaro/GSK, ImmunoGen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, NCI, Bristol Mye. G.M. Bariani: Financial Interests, Personal, Research Grant: Mabxience; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Libbs. P.A. Cassier: Financial Interests, Personal, Advisory Board: Merck Serono/EMD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Advisor: OSE immunotherapeutics; Financial Interests, Institutional, Invited Speaker: Abbvie, Amgen, Blueprint, Exelixis, GSK, Janssen, Novartis, Roche, Taiho, LOXO/Eli Lilly; Non-Financial Interests, Institutional, Product Samples: plexxikon, Novartis, MSD, AstraZeneca, GSK. A. Marabelle: Financial Interests, Institutional, Funding, funding to institution during the conduct of the study: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); Financial Interests, Personal, Other, honorarium: MSD; Financial Interests, Personal, Research Grant: Fondation MSD Avenir and Bristol M ers Squibb; Financial Interests, Personal, Speaker's Bureau: Bristol Myers Squibb and MSD. A.R. Hansen: Financial Interests, Personal, Advisory Board: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune; Financial Interests, Personal, Research Grant: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune; Financial Interests, Personal, Research Grant, research funding outside the submitted work: Boston Medical. A. De Jesus-Acosta: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Rahway, NJ, USA. W.H. Miller: Financial Interests, Personal, Other, serving as a consultant: BMS, Merck & Co., Inc., Rahway, NJ, USA, Roche, Novartis, Amgen, GSK, and Sanofi. A. Italiano: Financial Interests, Personal, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; AstraZeneca; Merck Serono; and Bayer; Financial Interests, Personal, Other, Personal fees: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; AstraZeneca; Bayer; Bristol Myers Squibb; Epizyme; and Roche. L. Yao: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. A. Gozman: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. F.J. Jin: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. M. Maio: Financial Interests, Personal, Advisory Board: Roche; Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Incyte; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Other, Honoraria: Roche, Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sciclone; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Stocks/Shares: Epigen Therapeutics, and Theravance. All other authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

O'Malley, D., et al. (2022). "19TiP SGNTUC-019 phase II basket study of tucatinib and trastuzumab in solid tumors with human epidermal growth factor receptor 2 alterations: Uterine and cervical cancer cohorts." Annals of Oncology 33(Supplement 5): S389-S390.
	Background: The prognosis of locally-advanced unresectable or metastatic (LA/M) cervical and uterine cancer remains poor, with HER2 alterations occurring in 0.5-21% of cervical cancers and 2-80% of uterine cancers, respectively. Tucatinib (TUC), a highly selective HER2 directed TKI, is approved in combination with trastuzumab (Tras) and capecitabine in multiple regions for HER2+ metastatic breast cancer and is being investigated in other HER2+ cancers, including LA/M cervical and uterine cancer. SGNTUC-019 (NCT04579380) is an open-label, international phase II basket study evaluating TUC and Tras in adult patients (pts) with LA/M HER2+ or HER2-mutated solid tumors. Trial design: SGNTUC-019 will evaluate TUC and Tras in pts with previously treated, LA/M solid tumors that display HER2 overexpression/amplification or activating mutations, including HER2+ cervical and uterine cancer cohorts. Pts will receive TUC 300 mg PO BID and Tras 8 mg/kg IV on Cycle 1 Day 1 and 6 mg/kg q21 days from Cycle 2 Day 1. HER2+ cervical and uterine cancer cohorts will enroll 12 pts each with potential for expansion up to 30 pts. Pts with HER2-mutated cervical, uterine, and other gynecologic cancers may enroll in a pooled cohort of 30 pts with HER2-mutated solid tumor types. Eligible pts must have progressed on or after their last systemic therapy, with prior platinum-based chemotherapy +/- bevacizumab required in pts with metastatic cervical cancer. Pts must have ECOG PS <=1, adequate organ function, and have not received HER2-directed therapy; pts with uterine serous carcinoma may have received prior Tras. HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH, or by HER2 amplification/mutation in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. The primary endpoint is confirmed ORR per investigator. DCR, DOR, PFS, OS, safety, and PK are secondary endpoints. Disease assessments per RECIST 1.1 will occur q6 weeks for 24 weeks, then q12 weeks. QoL will be evaluated q2 cycles using EQ-5D-5L. Enrollment is now open in Europe, the US, and Asia Pacific. Clinical trial identification: NCT04579380. Legal entity responsible for the study: Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA. Funding(s): Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA. Disclosure: D. O'Malley: Financial Interests, Personal and Institutional, Research Grant, Consultancy: AbbVie; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Agenus; Financial Interests, Personal, Other, Consultancy: Ambry; Financial Interests, Personal, Other, Consultancy: Arquer; Financial Interests, Personal and Institutional, Research Grant, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celsion; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Clovis; Financial Interests, Personal, Other, Consultancy: Corcept; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: Elevar; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Genentech/Roche; Financial Interests, Personal and Institutional, Research Grant, Consultancy: GOG Fnd; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Immunogen; Financial Interests, Personal and Institutional, Research Grant: Inc. Research; Financial Interests, Personal and Institutional, Research Grant: InVentiv Health; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Iovance; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Janssen; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Johnson & Johnson; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Mersana; Financial Interests, Personal, Other, Consultancy: Myriad; Financial Interests, Personal, Other, Consultancy: Novartis Novocure; Financial Interests, Personal, Other, Consultancy: Regeneron; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Rubis; Financial Interests, Personal, Other, Consultancy: SDPOnc; Financial Interests, Personal, Other, Consultancy: Seagen Inc.; Financial Interests, Personal, Research Grant, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Inxmed; Financial Interests, Personal and Institutional, Research Grant: Ajinomoto; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Cerulean; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: Ergomed; Financial Interests, Personal and Institutional, Research Grant: GenMab; Financial Interests, Personal and Institutional, Research Grant: Ludwig Cancer Research; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: New Mexico CCA; Financial Interests, Personal and Institutional, Research Grant: Novocure; Financial Interests, Personal and Institutional, Research Grant: PRA Int'l; Financial Interests, Personal and Institutional, Research Grant: Regeneron; Financial Interests, Personal and Institutional, Research Grant: SDPOnc; Financial Interests, Personal and Institutional, Research Grant: Seagen Inc.; Financial Interests, Personal and Institutional, Research Grant: Serono; Financial Interests, Personal and Institutional, Research Grant: Stemcentrx; Financial Interests, Personal and Institutional, Research Grant: Tarveda; Financial Interests, Personal and Institutional, Research Grant: Tesaro/GSK; Financial Interests, Personal and Institutional, Research Grant: Tracon Pharma; Financial Interests, Personal and Institutional, Research Grant: VentiRx; Financial Interests, Personal and Institutional, Research Grant: Yale University; Financial Interests, Personal, Invited Speaker: Sorrento; Financial Interests, Personal, Other, Consultancy: Takeda; Financial Interests, Personal, Other, Consultancy: Tesaro/GSK; Financial Interests, Personal, Other, Consultancy: Toray. F.J. Jin: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Ownership Interest: Merck; Financial Interests, Personal, Other, Travel Expenses: Merck. J.D. Ramos: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc. Q. Tan: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: Seagen Inc. B.J. Monk: Financial Interests, Personal, Other, Consultant: Agenus; Financial Interests, Personal, Other, Consultant: Akeso Bio; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, Consultant: Aravive; Financial Interests, Personal, Other, Speaker/Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Bayer; Financial Interests, Personal, Other, Speaker/Consultant: Clovis; Financial Interests, Personal, Other, Speaker/Consultant: Eisai; Financial Interests, Personal, Other, Consultant: Elevar; Financial Interests, Personal, Other, Consultant: EMD Merck; Financial Interests, Personal, Other, Consultant: Genmab/Seagen; Financial Interests, Personal, Other, Consultant: GOG Foundation; Financial Interests, Personal, Other, Consultant: Gradalis; Financial Interests, Personal, Other, Consultant: ImmunoGen; Financial Interests, Personal, Other, Consultant: Karyopharm; Financial Interests, Personal, Other, Consultant: Iovance; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Personal, Other, Speaker/Consultant: Merck; Financial Interests, Personal, Other, Consultant: Mersana; Financial Interests, Personal, Other, Honorarium: Novartis; Financial Interests, Personal, Other, Consultant: Novocure; Financial Interests, Personal, Other, Consultant: Myriad; Financial Interests, Personal, Other, Consultant: OncoC4; Financial Interests, Personal, Other, Consultant: Pieris; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Puma; Financial Interests, Personal, Other, Consultant: Regeneron; Financial Interests, Personal, Other, Speaker/Consultant: Roche/Genentech; Financial Interests, Personal, Other, Consultant: Sorrento; Financial Interests, Personal, Other, Speaker/Consultant: Tesaro/GSK; Financial Interests, Personal, Other, Consultant & Investigator: US Oncology Research; Financial Interests, Personal, Other, Consultant: VBL.Copyright © 2022 European Society for Medical Oncology

O'Malley David, M., et al. (2022). "Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 40(7): 752-761.
	Purpose: Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) tumors, including endometrial cancer, in the nonrandomized, open-label, multicohort, phase II KEYNOTE-158 study (NCT02628067). We report efficacy and safety outcomes for patients with MSI-H/dMMR endometrial cancer enrolled in KEYNOTE-158.; Methods: Eligible patients from cohorts D (endometrial cancer, regardless of MSI-H/dMMR status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR endometrial cancer received pembrolizumab 200 mg once every 3 weeks for 35 cycles. The primary end point was objective response rate per RECIST version 1.1 by independent central radiologic review. Secondary end points included duration of response, progression-free survival, overall survival, and safety.; Results: As of October 5, 2020, 18 of 90 treated patients (20%) had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (patients who received ≥ 1 dose of pembrolizumab and had ≥ 26 weeks of follow-up; N = 79), the median time from first dose to data cutoff was 42.6 (range, 6.4-56.1) months. The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months, and median overall survival was not reached (95% CI, 27.2 months to not reached). Among all treated patients, 76% had ≥ 1 treatment-related adverse event (grades 3-4, 12%). There were no fatal treatment-related events. Immune-mediated adverse events or infusion reactions occurred in 28% of patients (grades 3-4, 7%; no fatal events).; Conclusion: Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.; Competing Interests: David M. O'MalleyConsulting or Advisory Role: Janssen Oncology, AstraZeneca, Clovis Oncology, Tesaro, Novocure, AbbVie, Genentech/Roche, OncoQuest, Immunogen, GOG Foundation, Translational Genomics Research Institute, Agenus, Marker Therapeutics, Eisai, Genelux, Iovance Biotherapeutics, Ambry Genetics, Tarveda Therapeutics, Leap Therapeutics, Myriad Genetics, GlaxoSmithKline, Regeneron, Sorrento Therapeutics, Rubius Therapeutics, Elevar Therapeutics, Novartis, Seattle Genetics, BBI Healthcare, Arquer Diagnostics, Toray Medical, Takeda, InxMed, Celsion, Roche Diagnostics MSAResearch Funding: Amgen (Inst), AstraZeneca (Inst), Genentech/Roche (Inst), Regeneron (Inst), Immunogen (Inst), Janssen Research & Development (Inst), Clovis Oncology (Inst), EMD Serono (Inst), Ergomed (Inst), Ajinomoto (Inst), Immunogen (Inst), Cerulean Pharma (Inst), PharmaMar (Inst), Array BioPharma (Inst), Bristol Myers Squibb (Inst), Agenus (Inst), Tesaro (Inst), TRACON Pharma (Inst), Genmab (Inst), Seattle Genetics (Inst), Iovance Biotherapeutics (Inst), Leap Therapeutics (Inst), Merck (Inst), AbbVie/Stemcentrx (Inst), AbbVie (Inst), Mersana (Inst), Eisai (Inst), BBI Healthcare (Inst), Sumitomo Dainippon Pharma Oncology (Inst) Giovanni Mendonca BarianiConsulting or Advisory Role: LibbsResearch Funding: mAbxience, Merck Sharp & Dohme, Bristol Myers SquibbTravel, Accommodations, Expenses: Lilly Philippe A. CassierHonoraria: Novartis, Roche/Genentech, Amgen, AstraZeneca, Merck SeronoResearch Funding: Novartis (Inst), Roche/Genentech (Inst), Lilly (Inst), Blueprint Medicines (Inst), Bayer (Inst), AstraZeneca (Inst), Celgene (Inst), Plexxikon (Inst), AbbVie (Inst), Bristol Myers Squibb (Inst), Merck Serono (Inst), Merck Sharp & Dohme (Inst), Taiho Pharmaceutical (Inst), Toray Industries (Inst), Transgene (Inst), Loxo (Inst), GlaxoSmithKline (Inst), Innate Pharma (Inst), Janssen (Inst)Travel, Accommodations, Expenses: Roche, Amgen, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Netris Pharma, Bayer, Merck Serono Aurelien MarabelleStock and Other Ownership Interests: PEGASCY (Inst), HiFiBiO Therapeutics, Shattuck Labs, Centessa Pharmaceuticals (Inst)Honoraria: Bristol Myers Squibb, AstraZeneca/MedImmune, OncovirConsulting or Advisory Role: Lytix Biopharma, EISAI, Pierre Fabre, AstraZeneca, Servier, Roche, Redx Pharma, Sotio, Innate Pharma, ImCheck therapeutics, MSD, OSE Immunotherapeutics, HiFiBiO Therapeutics, MedinCell, Centessa PharmaceuticalsSpeakers' Bureau: BMSResearch Funding: Bristol Myers Squibb (Inst), Boehringer Ingelheim (Inst), Transgene (Inst), MSD (Inst)Patents, Royalties, Other Intellectual Property: Monoclonal antibodies against CD81 (Stanford University)Travel, Accommodations, Expenses: MSD, AstraZeneca Aaron R. HansenConsulting or Advisory Role: Merck, GlaxoSmithKline, Bristol Myers Squibb, Eisai, Novartis, AstraZenecaResearch Funding: Karyopharm Therapeutics (Inst), Merck (Inst), Bristol Myers Squibb (Inst), Boehringer Ingelheim, GlaxoSmithKline (Inst), Roche/Genentech (Inst), Janssen (Inst), AstraZeneca/MedImmune (Inst), Astellas Pharma (Inst), BioNTech (Inst), Pfizer/EMD Serono (Inst), Neoleukin Therapeutics (Inst) Ana De Jesus AcostaConsulting or Advisory Role: MerckResearch Funding: Merck (Inst), AstraZeneca (Inst) Wilson H. Miller JrHonoraria: Bristol Myers Squibb Foundation, Merck, Roche, Novartis, GlaxoSmithKline, Mylan, EMD Serono, AmgenConsulting or Advisory Role: Bristol Myers Squibb, Merck, Roche, Novartis, Amgen, GlaxoSmithKline, Mylan, EMD SeronoResearch Funding: Bristol Myers Squibb (Inst), Novartis (Inst), GlaxoSmithKline (Inst), Roche (Inst), AstraZeneca (Inst), Merck (Inst), MethylGene (Inst), Bayer (Inst), Amgen (Inst), MedImmune (Inst), Pfizer (Inst), Esperas Pharma (Inst), Astellas Pharma (Inst), Sanofi (Inst), Incyte (Inst), Array BioPharma (Inst), Exelixis (Inst), Mimic Technologies (Inst), Ocellaris Pharma (Inst), Canadian Institutes of Health Research (CIHR) (Inst), Canadian Research Society (Inst), Terry Fox Research Institute (Inst), Samuel Waxman Cancer Research Foundation (Inst), Canadian Cancer Society Research Institute (CCSRI) (Inst) Antoine ItalianoHonoraria: Bayer, Daiichi Sankyo, Lilly, Epizyme, Novartis, Roche, IPSENConsulting or Advisory Role: Roche, Daiichi Sankyo, Immune Design, Epizyme, Bayer, LillyResearch Funding: Roche, Bayer, AstraZeneca/MedImmune, PharmaMar, MSD Oncology, Merck SeronoPatents, Royalties, Other Intellectual Property: BMS Lei XuEmployment: MerckStock and Other Ownership Interests: Merck Fan JinEmployment: MerckStock and Other Ownership Interests: MerckTravel, Accommodations, Expenses: Merck Kevin NorwoodEmployment: Merck Michele MaioStock and Other Ownership Interests: Theravance, Epigen TherapeuticsHonoraria: Bristol Myers Squibb, AstraZeneca, Roche, MSD, Merck, Amgen, Pierre Fabre, Alfasigma, Sanofi, LillyConsulting or Advisory Role: Bristol Myers Squibb, Roche, AstraZeneca, MSD, Merck, Pierre Fabre, AlfasigmaPatents, Royalties, Other Intellectual Property: DNA Hypomethylating agents for cancer therapyTravel, Accommodations, Expenses: Bristol Myers Squibb, AstraZeneca, Roche, MSD, Merck, Amgen, Pierre Fabre, AlfasigmaNo other potential conflicts of interest were reported.

O'Malley David, M., et al. (2023). "PARP Inhibitors in Ovarian Cancer: A Review." Targeted oncology 18(4): 471-503.
	Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the ovarian cancer (OC) treatment landscape. This narrative review provides a comprehensive overview of data for the PARPis olaparib, niraparib, and rucaparib in patients with OC and discusses their role in disease management, with a focus on the use of PARPis as maintenance therapy in the United States (US). Olaparib was the first PARPi to be approved as first-line maintenance monotherapy in the US, with maintenance niraparib subsequently approved in the first-line setting. Data also support the efficacy of rucaparib as first-line maintenance monotherapy. PARPi maintenance combination therapy (olaparib plus bevacizumab) also provides benefit in patients with newly diagnosed advanced OC whose tumors tested positive for homologous recombination deficiency (HRD). Biomarker testing is critical in the newly diagnosed setting to identify patients most likely to benefit from PARPi maintenance therapy and guide treatment decisions. Clinical trial data support the use of PARPis (olaparib, niraparib, rucaparib) as second-line or later maintenance therapy in patients with platinum-sensitive relapsed OC. Although distinct differences in tolerability profile were observed between PARPis, they were generally well tolerated, with the majority of adverse events managed by dose modification. PARPis had no detrimental effect on patients' health-related quality of life. Real-world data support the use of PARPis in OC, although some differences between PARPis are apparent. Data from trials investigating novel combination strategies, such as PARPis plus immune checkpoint inhibitors, are awaited with interest; the optimal sequencing of novel therapies in OC remains to be established. (© 2023. The Author(s).)

O'Malley David, M., et al. (2022). "Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 40(7): 762-771.
	Purpose: Balstilimab (antiprogrammed death-1) and zalifrelimab (anticytotoxic T-lymphocyte-associated antigen-4) are two new checkpoint inhibitors emerging as promising investigational agents for the treatment of advanced cervical cancer. This phase II trial (ClinicalTrials.gov identifier: NCT03495882) evaluated the combination of balstilimab plus zalifrelimab in patients with recurrent and/or metastatic cervical cancer who relapsed after prior platinum-based therapy.; Patients and Methods: Patients were intravenously dosed with balstilimab 3 mg/kg once every 2 weeks and zalifrelimab 1 mg/kg once every 6 weeks, for up to 24 months. The primary end point was objective response rate (ORR, RECIST version 1.1, assessed by independent central review). Secondary end points included duration of response, safety and tolerability, and survival.; Results: In total, 155 women (median age, 50 years [range, 24-76 years]) were enrolled and treated with balstilimab plus zalifrelimab; 125 patients had measurable disease at baseline and one prior line of platinum-based therapy in the advanced setting, and these patients constituted the efficacy-evaluable population. The median follow-up was 21 months. The confirmed ORR was 25.6% (95% CI, 18.8 to 33.9), including 10 complete responders and 22 partial responders, with median duration of response not reached (86.5%, 75.5%, and 64.2% at 6, 9, and 12 months, respectively). The ORRs were 32.8% and 9.1% in patients with programmed death ligand-1-positive and programmed death ligand-1-negative tumors, respectively. For patients with squamous cell carcinoma, the ORR was 32.6%. The overall disease control rate was 52% (95% CI, 43.3 to 60.6). Hypothyroidism (14.2%) and hyperthyroidism (7.1%) were the most common immune-mediated adverse events.; Conclusion: Promising and durable clinical activity, with favorable tolerability, was seen in this largest trial to date evaluating dual programmed death-1/cytotoxic T-lymphocyte-associated antigen-4 blockade in patients with recurrent and/or metastatic cervical cancer. Further investigation of the balstilimab and zalifrelimab combination in this setting is continuing.; Competing Interests: David M. O'MalleyConsulting or Advisory Role: Janssen Oncology, AstraZeneca, Clovis Oncology, Tesaro, Novocure, AbbVie, Genentech/Roche, OncoQuest, Immunogen, GOG Foundation, Translational Genomics Research Institute, Agenus, Marker Therapeutics, Eisai, Genelux, Iovance Biotherapeutics, Ambry Genetics, Tarveda Therapeutics, Leap Therapeutics, Myriad Genetics, GlaxoSmithKline, Regeneron, Sorrento Therapeutics, Rubius Therapeutics, Elevar Therapeutics¸ Novartis, Seattle Genetics, BBI Healthcare, Arquer Diagnostics¸ Toray Medical, Takeda, InxMed, Celsion, Roche Diagnostics MSAResearch Funding: Amgen (Inst), AstraZeneca (Inst), Genentech/Roche (Inst), Regeneron (Inst), Immunogen (Inst), Janssen Research & Development (Inst), Clovis Oncology (Inst), EMD Serono (Inst), Ergomed (Inst), Ajinomoto (Inst), Immunogen (Inst), Cerulean Pharma (Inst), PharmaMar (Inst), Array BioPharma (Inst), Bristol Myers Squibb (Inst), Agenus (Inst), Tesaro (Inst), TRACON Pharma (Inst), Genmab (Inst), Seattle Genetics (Inst), Iovance Biotherapeutics (Inst), Merck (Inst), AbbVie/Stemcentrx (Inst), AbbVie (Inst), Mersana (Inst), Eisai (Inst), BBI Healthcare (Inst), Sumitomo Dainippon Pharma Oncology (Inst), Bradley J. MonkLeadership: US OncologyHonoraria: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai¸ Geistlich Pharma, Genmab/Seattle Genetics, ImmunoGen, Immunomedics, Incyte, Iovance Biotherapeutics, Laekna Health Care, Mersana, Merck, Myriad Pharmaceuticals, NuCana, OncoMed, OncoQuest, OncoSec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, GOG Foundation, Starton Therapeutics, Elevar Therapeutics, Novocure, Iovance Biotherape tics, Gradalis, Karyopharm TherapeuticsConsulting or Advisory Role: AbbVie, Advaxis, Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoID, Clovis Oncology, Deciphera Pharmaceuticals, Eisai¸ Geistlich Pharma, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Immunomedics, Iovance Biotherapeutics, Laekna Health Care, Mersana, Merck, Myriad Pharmaceuticals, NuCana, OncoMed, OncoQuest, OncoSec, Perthera, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Senti Biosciences, Takeda, Tarveda Therapeutics, Tesaro/GSK, Vavotar Life Sciences, Vascular Biogenics, Vigeo Therapeutics, Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, Novocure, ChemocareSpeakers' Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GSK, MerckResearch Funding: Amgen (Inst), Genentech (Inst), Lilly (Inst), Janssen (Inst), Array BioPharma (Inst), Tesaro (Inst), Morphotek (Inst), Pfizer (Inst), Advaxis (Inst), AstraZeneca (Inst), ImmunoGen (Inst), Regeneron (Inst), NuCana (Inst) Marilyn HuangConsulting or Advisory Role: Tesaro, Seattle Genetics, Aptitude Health, Agenus, Cooper Surgical, touchExpert opinionsResearch Funding: Merck (Inst) Tarek M. MeniawyHonoraria: AstraZeneca/MedImmuneConsulting or Advisory Role: AstraZeneca/MedImmune, Novartis, GlaxoSmithKline, BMSResearch Funding: Bristol Myers Squibb (Inst), BeiGene (Inst), Incyte (Inst), AstraZeneca/MedImmune (Inst), Regeneron (Inst), Bayer (Inst), Merck Serono (Inst), Roche/Genentech (Inst)Travel, Accommodations, Expenses: BMS Waldo Ortuzar FeliuEmployment: AgenusStock and Other Ownership Interests: AgenusTravel, Accommodations, Expenses: Agenus Marek AncukiewiczEmployment: Agenus, LFB Biotechnologies, Boston Scientific (I)Stock and Other Ownership Interests: Agenus, Boston Scientific (I) Iwona LugowskaHonoraria: Roche, Agen7s, MSD, AmgenResearch Funding: Roche (Inst), Novartis (Inst)Travel, Accommodations, Expenses: Roche/GenentechNo other potential conflicts of interest were reported.

O'Malley David, M., et al. (2022). "Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma." Gynecologic Oncology 167(3): 404-413.
	Objective: ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib.; Methods: Patients were randomized 2:1 to receive rucaparib 600 mg twice daily or placebo. Molecular features (genomic alterations, BRCA1 promoter methylation) and baseline clinical characteristics were evaluated for association with exceptional benefit (progression-free survival ≥2 years) versus progression on first scan (short-term subgroup) and other efficacy outcomes.; Results: Rucaparib treatment was significantly associated with exceptional benefit compared with placebo: 79/375 (21.1%) vs 4/189 (2.1%), respectively (p < 0.0001). Exceptional benefit was more frequent among patients with favorable baseline clinical characteristics and with carcinomas harboring molecular evidence of homologous recombination deficiency (HRD). A comparison between patients who derived exceptional benefit from rucaparib and those in the short-term subgroup revealed both clinical markers (no measurable disease at baseline, complete response to latest platinum, longer penultimate platinum-free interval) and molecular markers (BRCA1, BRCA2, RAD51C, and RAD51D alterations and genome-wide loss of heterozygosity) significantly associated with exceptional benefit.; Conclusions: Exceptional benefit in ARIEL3 was more common in, but not exclusive to, patients with favorable clinical characteristics or molecular features associated with HRD. Our results suggest that rucaparib can deliver exceptional benefit to a diverse set of patients with recurrent high-grade ovarian carcinoma.; Competing Interests: Declaration of Competing Interest DMO reports personal fees from consulting and/or advisory board participation from Clovis Oncology, AbbVie, Agenus, Ambry, Amgen, Arquer Diagnostics, AstraZeneca, Celsion Corp, Corcept Therapeutics, Eisai, Elevar, Genelux, Genentech/Roche, GOG Foundation, Immunogen, Inxmed, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Merck, Mersana, Myriad Genetics, Novartis, Novocure, Regeneron, Roche Diagnostics MSA, Rubis, SeaGen, SDP Oncology (BBI), Takeda, and Tesaro/GlaxoSmithKline, Toray; research funding (all funding to institution) from Clovis Oncology, AbbVie, Agenus, Ajinomoto, Amgen, Array Biopharma, AstraZeneca, Bristol Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, Ergomed, Genentech/Roche, GenMab, GOG Foundation, Immunogen, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen/Johnson & Johnson, Ludwig Institute for Cancer Research, Merck, National Cancer Institute, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron, SeaGen, Serono, Stemcentrx, Tesaro/GlaxoSmithKline, Tracon Pharmaceuticals, VentiRx, and Yale University; and has given a presentation on ovarian cancer at the National Comprehensive Cancer Network. AMO reports grants to his institution from AstraZeneca; has served on steering committees for Clovis Oncology, AstraZeneca (uncompensated), and Tesaro (uncompensated); has served in an advisory role for AstraZeneca and GlaxoSmithKline (uncompensated); and has acted as a principal investigator on investigator-initiated trials with agents from Clovis Oncology, AstraZeneca, and GlaxoSmithKline. DL reports institutional research funding from Clovis Oncology, AstraZeneca, Corcept Therapeutics, GlaxoSmithKline, Genmab, ImmunoGen, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, and Seagen; consulting fees from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and PharmaMar; payment or honoraria for lectures from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Seagen; support for attending meetings and/or travel from AstraZeneca, PharmaMar, and Roche; participation on a data safety monitoring board or advisory board for Clovis Oncology, Agenus, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche; and serves on the board of directors for GCIG and as chair of GCA for ENGOT. CA has served on a steering committee for AbbVie and Genentech; has served as a principle investigator for studies by Clovis Oncology, AbbVie, AstraZeneca, and Genentech; served on advisory boards for AbbVie, AstraZeneca/Merck, Blueprint Medicine, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech; and serves on the board of directors (unpaid) for GOG Foundation and NRG Oncology. AO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca Farmaceutica Spain, AstraZeneca, Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe Limited, EMD Serono, F. Hoffmann-La Roche, GlaxoSmithKline, Got It Consulting, Immunogen, KL Logistics, Medison Pharma, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure GmbH, PharmaMar, prIME Oncology, Roche Farma, Shattuck Labs, Sutro Biopharma, Tesaro Bio GmbH, Tesaro Bio Spain, and Tesaro; and support for attending meetings and/or travel from AstraZeneca, Roche, and PharmaMar. AD has served in a consulting or advisory role for Precision Oncology Australia, Shire Pharmaceuticals, and Specialised Therapeutics Australia; and sits on the scientific advisory board for A2A Pharmaceuticals. NC reports institutional research funding from Clovis Oncology; serving in a consulting or advisory role for Clovis Oncology, AstraZeneca, BIOCAD, Eisai, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Mersana, Novartis, Nuvation Bio, Oncxerna, Pfizer, PharmaMar, Roche, and Tesaro; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Novartis; and support for attending meetings and/or travel from AstraZeneca. JIW has received research support from AstraZeneca. ARC reports consulting fees for advisory boards for AstraZeneca; payment or honoraria for speakers bureaus for Clovis Oncology and Merck Sharp & Dohme; support for attending meetings and/or travel from Tesaro; and institutional research funding from Clovis Oncology and AstraZeneca. GS reports royalties or licenses from Merck Sharp & Dohme Italia; consulting fees from Tesaro Bio Italy and Johnson & Johnson; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology Italy. AL has served on advisory boards for Clovis Oncology, Ability Pharmaceuticals, AstraZeneca, BIOCAD, GamaMabs, Genmab/Seattle Genetics, GlaxoSmithKline, Gritstone, Merck Serono, Merck Sharp & Dohme, and Tesaro; steering committee for Merck Sharp & Dohme; reports institutional support for clinical trials or academic research from Clovis Oncology, Ability Pharmaceuticals, Agenus, AstraZeneca, Incyte, Inivata, Iovance, Merck Sharp & Dohme, Pfizer, Roche, Sanofi, and Tesaro; and reports boarding and travel expenses for congress activities from Clovis Oncology, AstraZeneca, and Roche. RWH reports consulting fees from Clovis Oncology, AstraZeneca, and GlaxoSmithKline; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca, and GlaxoSmithKline. MAG has served on speakers' bureaus for Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and PharmaMar; and reports support for attending meetings and/or travel from GlaxoSmithKline. PCF reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck Sharp & Dohme; support for attending meetings and/or travel from Merck Sharp & Dohme and Pfizer. JCG reports consulting fees from AstraZeneca, Bristol Myers Squibb, Eisai, and Merck Sharp & Dohme; payment or honoraria for lectures, presentations, spe kers bureaus, manuscript writing, or educational events from AstraZeneca, Bristol Myers Squibb, Ipsen, and Merck Sharp & Dohme Australia; support for attending meetings and/or travel from AstraZeneca; participation on a data safety monitoring board or advisory board for Bristol Myers Squibb and Janssen; and stock or stock options for ICON Cancer Care, Australia. EMS reports institutional research funding from Clovis Oncology. LM, SG, KL, and TK are employees of Clovis Oncology and may own stock or have stock options in that company. JAL has received lecture fees from Clovis Oncology, AstraZeneca, GlaxoSmithKline, and Pfizer; served on advisory boards for Clovis Oncology, Amgen, Artios Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Merck/Merck Sharp & Dohme, Nuvation, Pfizer, Regeneron, VBL Therapeutics, and Tesaro/GlaxoSmithKline; and received research grants from AstraZeneca and Merck/Merck Sharp & Dohme. RLC reports grants or contracts from Clovis Oncology, AstraZeneca, Gateway Foundation, Genelux, Genmab, Janssen, Merck, and Roche/Genentech; consulting fees from Clovis Oncology, Agenus, Alkermes, AstraZeneca, Deciphera, Genelux, Genmab, GlaxoSmithKline, Immunogen, Janssen, OncoQuest, OncXerna, Onxeo, Regeneron, and Roche/Genentech. (Copyright © 2022. Published by Elsevier Inc.)

O'Malley, D. M., et al. (2022). "Real-world use, tolerability, and dose modifications of PARP inhibitors in ovarian cancer." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Tolerability is a key consideration when selecting a PARP inhibitor (PARPi) for ovarian cancer (OC). Here we expand on earlier work (Arend et al 2021) to further characterize real-world tolerability and dose modifications in US patients (pts) with OC receiving PARPi therapy. Method(s): A retrospective cohort of OC pts starting olaparib (ola), niraparib (nir) or rucaparib (ruc) between Jan 2017 and Dec 2020 was identified from MarketScanVR Commercial/Medicare Supplemental databases, increasing the period covered and number of pts included vs our previous analysis. Pts were followed up from first PARPi prescription (index) for >=30 days until end of study period, disenrollment or death; baseline was 6 months pre-index. Clinical events of interest (CEIs; acute myeloid leukemia/myelodysplastic syndromes, anemia, leukopenia/neutropenia, thrombocytopenia, acute kidney injury, arthralgia, constipation, diarrhea, nausea, vomiting, dermatitis/rash/photosensitivity, fatigue, hypertension, infection, insomnia, pneumonitis, transaminitis) were identified via ICD-9/10 codes. Multivariable Cox regression compared the likelihood of CEIs, dose modifications and hospitalizations between PARPis, adjusting for baseline CEI, Charlson Comorbidity Index score, prior bevacizumab and cancer-related surgery. Persistence was defined as no PARPi treatment gaps of >90 days in pts with >=6 months' continuous enrollment. Result(s): Overall, 637, 538 and 227 pts received ola, nir and ruc, respectively (median [IQR] follow-up 10.5 [13.4] months). Baseline characteristics were similar across groups. The proportion of pts initiating PARPi at the highest indicated dose was 89.2%, 57.6% and 89.9% for ola, nir and ruc, respectively; 22.6%, 34.8% and 28.6%, respectively, required dose decreases. The likelihood of experiencing CEIs varied across the PARPis after adjusting for a priori confounders as shown in the table. Persistence with index PARPi was higher with ola (83.4%) vs nir (73.3%; P<0.001) and similar vs ruc (80.2%; P>0.05). Among all pts, mean time to non-persistence was shorter with nir vs ola and ruc (6.4 vs 7.9 and 7.6 months, respectively; both P<0.05). CEIs by PARPi dose and calendar year will also be presented. Conclusion(s): This is the largest real-world comparison of PARPi use in OC pts reported to date. It supports differences between PARPis in persistence with therapy and risk of experiencing a CEI, even after adjusting for confounders.

O'Malley, D. M., et al. (2022). "Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study." Gynecologic Oncology 166(2): 245-253.
	Objective: Pembrolizumab demonstrated a clinically meaningful objective response rate in patients with previously treated, advanced MSI-H/dMMR endometrial cancer in the multicohort phase 2 KEYNOTE-158 study (ClinicalTrials.gov, NCT02628067). We present health-related quality of life (HRQoL) results for these patients.; Methods: This analysis included patients from cohorts D (endometrial cancer with any MSI status) and K (any MSI-H/dMMR solid tumor except colorectal) who had previously treated, advanced MSI-H/dMMR endometrial cancer. Patients received pembrolizumab 200 mg Q3W for 35 cycles. EORTC QLQ-C30 and EQ-5D-3L questionnaires were administered at baseline, at regular intervals during treatment, and 30 days after treatment discontinuation. Pre-specified exploratory analyses included changes from baseline to week 9 in QLQ-C30 global health status (GHS)/QoL and EQ-5D-3L visual analog scale (VAS) score for all patients and by best overall response.; Results: 84 of 90 enrolled patients completed ≥1 HRQoL questionnaire and were included in the analysis. QLQ-C30 and EQ-5D-3L compliance rates were 90% and 94%, respectively, at baseline, and 92% and 93% at week 9. Mean (95% CI) QLQ-C30 GHS/QoL scores improved from baseline to week 9 by 6.08 (0.71-11.46) points in the overall population, with greater improvement in patients who achieved complete or partial response (11.67 [5.33-18.00]-point increase). Mean (95% CI) EQ-5D-3L VAS scores improved by 6.00 (2.25-9.75) points in the overall population and 9.11 (5.24-12.98) points in patients with CR/PR.; Conclusions: Pembrolizumab maintained or improved HRQoL in patients with previously treated, advanced MSI-H/dMMR endometrial cancer, further supporting efficacy and safety results from KEYNOTE-158 and pembrolizumab use in this setting. (Copyright © 2022. Published by Elsevier Inc.)

O'Malley, D. M., et al. (2021). "RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer." Future oncology (London, England) 17(26): 3433-3443.
	Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for the treatment of cervical cancer, particularly in the setting of previously-treated, recurrent/metastatic disease. Here we describe the rationale and design of RaPiDS (NCT03894215), a two-arm Phase II study evaluating the safety, tolerability and efficacy of balstilimab administered alone or in combination with zalifrelimab in patients with advanced cervical cancer who progressed after first-line, platinum-based chemotherapy. Patients will be randomized in a 1:1 ratio. The primary end point is objective response rate, and key secondary objectives include safety, duration of response, progression-free survival, overall survival and quality of life outcomes.

O'Malley Patricia, A. (2023). "A Nonhormonal Selective NK3R Antagonist for Moderate to Severe Vasomotor Symptoms in Menopause." Clinical nurse specialist CNS 37(6): 259-261.
	Competing Interests: The author reports no conflicts of interest

O'Malley Patricia, A. (2024). "ZURZUVAE-The First Oral Treatment Approved for Postpartum Depression." Clinical nurse specialist CNS 38(1): 15-17.
	Competing Interests: The author reports no conflicts of interest.

Omar, S. S., et al. (2023). "Comparable Efficacy of Submucosal Platelet-Rich Plasma and Combined Platelet-Rich Plasma Noncrosslinked Hyaluronic Acid Injections in Vulvovaginal Atrophy: A Cancer Survivorship Issue." Journal of Women's Health 32(9): 1006-1020.
	Background: Cancer survivors are often reluctant to discuss sexual complaints with their oncologists and treatment is frequently unsatisfactory due to paucity of controlled studies and inapplicability of vaginal estrogen. We aimed to evaluate efficacy and tolerability of platelet-rich plasma (PRP) injections alone or in combination with noncrosslinked hyaluronic acid compared with standard therapy with topical hyaluronic acid gel in the management of cancer therapy-induced or aggravated vulvovaginal atrophy. Material(s) and Method(s): This prospective, parallel-group comparative study was conducted on 45 female patients with a history of cancer and complaining of symptoms of vulvovaginal atrophy either induced or aggravated by cancer treatment. Patients were randomly divided into three groups (A, B, and C). Group A patients received two submucosal vaginal PRP injections, group B patients received two similar injections of PRP combined with noncrosslinked hyaluronic acid, and group C received a topical vaginal hyaluronic acid gel applied three times weekly for 2 months. Main outcome measures were vulvovaginal atrophy symptom severity and vaginal health index (VHI) scores before treatment (v0), 1 month from baseline (v1), 2 months from baseline (v2), and 3 months after the last visit (v3). Result(s): Both groups A and B showed greater improvement of frequency of intercourse avoidance than group C. Group A showed greater improvement of dyspareunia than group C. Groups A and B demonstrated greater improvement of vaginal pH, fluid volume, and total VHI scores than group C. Short-term topical hyaluronic acid (HA) was not associated with any significant improvement of vaginal elasticity. Group B showed greater improvement of vaginal dryness and moisture scores than group C. Reported adverse events were injection-related pain in all patients of groups A and B and vaginal spotting in groups A and B. Conclusion(s): Both PRP and PRP-HA have comparable efficacy and patient-reported treatment satisfaction. PRP injections were better tolerated by patients than PRP-HA. Clinical trial registration number: NCT05782920.© Copyright 2023, Mary Ann Liebert, Inc., publishers 2023.

On, S. and A. Chang (2022). "Treatment of lymphoma with rituximab and chemotherapy during pregnancy." Leukemia & lymphoma 63(12): 2897-2904.
	Safety of chemoimmunotherapy during pregnancy for treatment of Non-Hodgkin's lymphoma (NHL) is controversial. We review 37 cases of mothers with high grade NHL treated with rituximab and concurrent chemotherapy during pregnancy. Majority (95%) of mothers were treated in their second and third trimester, and a median of 4 cycles of combination therapy was administered. Complete remission occurred in 14/17 (82%) mothers whose disease outcomes were reported. There were 2 spontaneous abortions and 1 trimester fetal death that occurred in 3 mothers who received treatment in their first and second trimesters. Among the 34 (92%) live births, there were 6 cases of respiratory/cardiac complications requiring intervention and 5 cases of hematologic abnormalities reported. This review highlights the efficacy and safety of chemoimmunotherapy for mothers treated in second and third trimester. Further data is needed to establish recommendations for management of mothers with aggressive NHL in their first trimester of pregnancy.

Onal, C., et al. (2022). "The impact of serum albumin-to-alkaline phosphatase ratio in cervical cancer patients treated with definitive chemoradiotherapy." Journal of Obstetrics and Gynaecology 42(6): 2426-2432.
	We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact StatementWhat is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established. Whatdothe results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR. Whatarethe implicationsof these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Onal, C., et al. (2021). "Impact of lymph node ratio in patients with stage IIIC endometrial carcinoma treated with postoperative radiotherapy." Future oncology (London, England) 17(25): 3321-3330.
	Aim: To evaluate the prognostic value of the lymph node ratio (LNR) and other clinicopathological factors in patients with stage IIIC endometrial cancer. Methods: Factors affecting overall survival (OS) and progression-free survival (PFS) were assessed in 397 patients with stage IIIC endometrial cancer treated with postoperative radiotherapy. Patients undergoing the removal of at least ten lymph nodes were included in the study. Results: The 5-year OS and PFS rates were 58% and 52%, respectively, with a median follow-up time of 35.7 months. The LNR cutoff value was 9.6%. In the multivariate analysis, advanced age (≥60 years), grade III tumor, presence of cervical stromal invasion, higher LNR and lack of adjuvant chemotherapy were independent predictors for worse OS and PFS. Conclusion: The LNR is an independent predictor for OS and PFS in patients with stage IIIC endometrial cancer treated with postoperative radiotherapy.

Onge Erin, S., et al. (2023). "Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms." The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians 39(6): 291-297.
	Objective: To review the safety, efficacy, and tolerability of fezolinetant for the treatment of vasomotor symptoms associated with menopause. Data Sources: A literature search was conducted through PubMed using the following search terms: fezolinetant, ES259564, SKYLIGHT, vasomotor symptoms, and menopause. Study Selection and Data Extraction: Selected articles included those which described clinical studies of the pharmacology, pharmacokinetics, efficacy, safety, or tolerability of fezolinetant. Data Synthesis: Fezolinetant works by inhibiting neurokinin B from binding to its receptor in the hypothalamus, thereby decreasing the occurrence of vasomotor symptoms. Clinical trials have demonstrated fezolinetant is superior to placebo in decreasing the frequency and severity of vasomotor symptoms. Common adverse effects associated with the use of fezolinetant include headache and gastrointestinal disturbances, as well as elevations in liver transaminase levels. Conclusions: Clinical practice guidelines for the treatment of vasomotor symptoms associated with menopause recommend hormone therapy as the most effective treatment option. Risks associated with hormone use may limit the use of this option in some patients. Neurokinin B inhibitors, like fezolinetant, target the physiologic cause of vasomotor symptoms. With the approval of fezolinetant, as well as elinzanetant which is currently in phase 3 clinical trials, providers and patients have additional nonhormonal treatment options for vasomotor symptoms associated with menopause.; Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. (© The Author(s) 2023.)

Onishi, C., et al. (2022). "Lymphoma during pregnancy in Japan: a multicenter retrospective cohort study." International Journal of Hematology 115(3): 382-390.
	Objective: This study was conducted to characterize lymphoma occurring during pregnancy and to investigate the outcomes of the patients and the fetuses.; Methods: Clinical data were gathered retrospectively from 29 patients at 13 participating institutions, and data from 28 eligible patients were analyzed.; Results: Six (21%) patients had Hodgkin lymphoma (HL) and 22 (79%) patients had non-Hodgkin lymphoma (NHL). All patients with HL presented with lymphadenopathy, but 15 (68%) of the 22 patients with NHL presented with extranodal sites only. At the median follow-up period of 1325 (range 6-4461) days, the 5-year overall survival rate was 63% for patients with NHL and 100% for patients with HL. Three of the 13 patients who received chemotherapy during pregnancy (23%) developed Pneumocystis jiroveci pneumonia (PCP). There was 1 intrauterine fetal death, 1 spontaneous abortion in the first trimester, and 15 (54%) preterm births.; Conclusion: This study showed a higher proportion of NHL than HL during pregnancy in Japan, which was inconsistent with the proportions observed in Western countries. The high incidence of maternal PCP and preterm birth suggested the need for improvements in our management of lymphoma during pregnancy. (© 2022. Japanese Society of Hematology.)

Ono, Y., et al. (2022). "Influence of laparoscopic surgery for endometriosis and its recurrence on perinatal outcomes." Reproductive Medicine and Biology 21(1): e12456.
	Purpose: It is unknown whether surgery for endometriosis or recurrence of endometriosis affects obstetric outcomes.; Methods: A total of 208 pregnant women with a history of endometriosis were analyzed. Patients who had endometriomas >3 cm and no history of laparoscopic surgery for endometriosis were defined as non-surgery group ( n = 60), while those who had a history of surgery for endometriosis ( n = 148) were defined as surgery group. We investigated the obstetric outcomes in 208 patients according to with or without postoperative recurrence of endometriosis and the time from surgery to pregnancy.; Results: Among 177 cases of on-going pregnancy, in surgery group, there were lower prevalence of placenta previa compared with non-surgery group (8.5% vs. 23.4%; p = 0.020). Subgroup analysis revealed a decreased prevalence of placenta previa in postoperative non-recurrence group (6.0%: p = 0.007) compared with non-surgery (23.4%) and postoperative recurrence group (28.6%). Placenta previa was more prevalent in the patients who got pregnant more than 2 years after surgery (20.0%) than the patients who got pregnant within 2 years (2.4%: p = 0.002). Multivariate analysis revealed that the surgery was associated with a reduction in placenta previa (OR: 0.32, 95% CI [0.11-0.90]; p = 0.032).; Conclusions: Pregnancy within two years after laparoscopic surgery for endometriosis may reduce placenta previa. (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Ono, Y., et al. (2023). "Effectiveness of Laparoscopic Adenomyomectomy on Perinatal Outcomes." Gynecology and Minimally Invasive Therapy 12(4): 211-217.
	Objectives: The objective of this study was to observe the influence of laparoscopic adenomyomectomy on perinatal outcomes.; Materials and Methods: The retrospective cohort study included 43 pregnant cases with adenomyosis who did not undergo laparoscopic surgery before pregnancy (nonsurgery group; 26 cases) and did (surgery group; 17 cases). To evaluate the impact of surgery on perinatal outcomes, nine obstetric complications including preterm delivery, hypertensive disorder of pregnancy, placental malposition, oligohydramnios, gestational diabetes mellitus, uterine rupture, abruptio placentae, and postpartum hemorrhage were selected. One obstetric complication was counted as one point (Maximum 9 points for one person). The obstetrical morbidity was compared by adding up the number of relevant events (0-9) between the two groups. Apgar score, umbilical artery pH (UApH), neonatal intensive care unit (NICU) admission, and neonatal death were also examined.; Results: The surgery group had a significantly lower prevalence of fetal growth restriction compared to the nonsurgery group (nonsurgery vs. surgery; 26.9%, 7/26 vs. 0%, 0/17: P = 0.031). No differences were found in the morbidity of the nine obstetric complications (19.2%, 45/234 vs. 13.7%, 21/153), gestational weeks (mean ± standard deviation, 37.2 ± 2.4 vs. 36.4 ± 3.2), birth weight (2573.6 ± 557.9 vs. 2555.4 ± 680.8 g), Apgar score (1, 5 min; 8.0 ± 0.7 vs. 7.7 ± 1.2, 8.9 ± 0.6 vs. 8.5 ± 1.8), UApH (7.28 ± 0.08 vs. 7.28 ± 0.06), NICU admission (26.9%, 7/26 vs. 41.2%, 7/17), and neonatal death (0%, 0%) between both groups.; Conclusion: Laparoscopic adenomyomectomy may not increase obstetric complications, although attention must be paid to uterine rupture during pregnancy.; Competing Interests: There are no conflicts of interest. (Copyright: © 2023 Gynecology and Minimally Invasive Therapy.)

Ooka, R., et al. (2023). "Evaluation of the role of intraoperative frozen section and magnetic resonance imaging in endometrial cancer." International Journal of Gynecology and Obstetrics 160(2): 554-562.
	Objective: To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. Method(s): This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. Result(s): Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P = 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P < 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. Conclusion(s): Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.Copyright © 2022 International Federation of Gynecology and Obstetrics.

Ooyama, T., et al. (2022). "Effects of Pegylated Liposomal Doxorubicin and CA125 Level Variability Analysis in Platinum-refractory/resistant Recurrent Ovarian Cancer." Anticancer Research 42(6): 3017-3022.
	Background/aim: Ovarian cancer is a disease with significant impact, because more than half of cases exhibit recurrence despite platinum therapy. The choice of drug for cases of recurrence remains controversial, but the current option is pegylated liposomal doxorubicin (PLD).; Patients and Methods: We retrospectively reviewed the use of PLD in patients with ovarian cancer refractory or resistant to platinum-based therapy at our Department. We also examined efficacy, predictive indices of efficacy, and adverse events as well.; Results: In this study of PLD monotherapy for 60 platinum-refractory/resistant recurrent ovarian cancers, there was a median progression-free survival (PFS) of 4 months, median overall survival (OS) of 11 months, and the disease control rate (DCR) was 71.7%. The treatment effect can be predicted by the reduction of CA125 level after 2 courses. Patients with an increase and decrease in CA125 after 2 cycles of PLD, respectively, had a median OS of 14.5 (2-60) and 8 (2-51) months and a median PFS of 6 (2-38) months and 3 (0-47) months.; Conclusion: PLD is clinically effective and useful because it provides a high DCR and is tolerable to adverse events. These findings can help support the use of PLD and guide physicians in their choice of treatment when encountering such cases. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Opławski, M., et al. (2022). "The Impact of Surgical Treatment with Adjuvant Chemotherapy for Ovarian Cancer on Disorders in the Urinary System and Quality of Life in Women." Journal of Clinical Medicine 11(5).
	Ovarian cancer is the fourth-most-common cause of death among all malignant cancers in women in Poland. This study aimed to compare the functioning of the urinary system and quality of life in women in the 12-month period following the completion of surgery or adjuvant treatment for ovarian cancer, with patients who underwent a hysterectomy for non-oncological reasons (control group). The study group consisted of 50 patients diagnosed with stage I−III ovarian cancer. Among 38 patients with type II ovarian cancer (group A), surgery followed by first-line chemotherapy was performed. Within this group of patients, 20 had stage I ovarian cancer, while 18 had stage II ovarian cancer. The study was performed at least 6 months after the final chemotherapy cycle, with no clinical, marker or radiological recurrence determined. On the other hand, in 12 patients with stage I type I ovarian cancer, oncological treatment consisted of only surgery, without the need for adjuvant chemotherapy, due to the low stage of the lesions (group B). In turn, the control group consisted of 50 women who underwent uterine removal for non-oncological reasons (group C). The assessment of quality of life was conducted using the questionnaires: Satisfaction with Life Scale (SWLS); Incontinence Impact Questionnaire, short form (IIQ-7); Urogenital Distress Inventory (UDI-6); and the Sexual Satisfaction Scale for 3, 6, 9, and 12 months after the conclusion of oncological treatment. During the follow-up, a significant reduction in the quality of everyday life and sexual life was noted among patients with ovarian cancer, more pronounced in group B, compared to the control group (p < 0.05). The risk of urinary incontinence is independent of the treatment regimen chosen for ovarian cancer. It is necessary to consider comprehensive psychological care and sexual therapy in patients with ovarian cancer and their families.

Oppenheim, S., et al. (2022). "Advance Care Planning in Patients with Metastatic Cancer: A Quality Improvement Initiative." JCO oncology practice 18(10): E1562-E1566.
	PURPOSE:An initiative aimed to increase the rate of advance care planning (ACP) activities for outpatients with metastatic cancer, an essential step to achieving goal concordant care. METHOD(S):Patients with metastatic cancer were identified by International Classification of Diseases-10 coding and later by oncologists' electronic health record documentation of metastatic tumor status. ACP activities were defined as either an ACP note, Advance Directive, Physician Orders for Life-Sustaining Therapy (POLST), or a Palliative Medicine (PM) consultation within the prior year. From 2017 to 2020, the initiative screened more than 5,000 total unique cancer patients per year. PM consultants were embedded in tumor boards, oncology care team meetings, and shared oncology clinic space. Quarterly reports were sent to 60 oncologists at three cancer care sites with data of their percentage of ACP activities for patients with metastatic cancer compared with their peers. Oncologists' identities were initially blinded, but later unblinded. Oncologists also received a monthly list of patients with metastatic cancer without ACP activities. RESULT(S):The rate of ACP activities for patients with metastatic cancer increased from a baseline of 37% in July 2017 to 57% by the end of 2020. PM consultations increased from 12% to 39% and ACP notes increased from 16% to 29% during the same interval. There was no change in Advance Directive (17%-20%) or POLST completion (7%-6%). CONCLUSION(S):ACP activities are an essential step to achieve goal concordant care, and this initiative successfully increased ACP activities for patients with metastatic cancer. However, given that the main source of increased ACP activities during this initiative was PM referrals, further progress will depend upon strengthening the oncology care teams' ACP skills and motivation for completion.Copyright © American Society of Clinical Oncology.

Orachum, P., et al. (2022). "Clinical outcomes of immunohistochemistry of the p53 Staining pattern in high-grade serous ovarian carcinoma." Obstetrics & Gynecology Science 65(5): 459-467.
	Objective: To investigate the prevalence of p53 mutations and associated factors between immunohistochemistry (IHC) and p53 staining patterns among patients with high-grade serous ovarian carcinoma (HGSOC).; Methods: This study is a retrospective review. A total of 62 patients with HGSOC underwent surgery at Srinagarind Hospital between January 2016 and December 2020. Histological examination was performed based on a combination of morphology and IHC staining with p53. The p53 immunostaining pattern was interpreted as a missense mutation, nonsense mutation, or a wild-type pattern. Missense (p53 overexpression pattern) and nonsense (null expression p53 pattern) mutations were considered p53 mutations. A wild-type pattern was defined as a p53 non-mutation.; Results: p53 mutations were identified in 93.6% of the patients. Subgroup analysis of the p53 mutation group between the p53 overexpression pattern and the p53 null expression pattern in terms of clinicopathological characteristics and initial treatment was performed. Patients with the p53 overexpression pattern had significantly more omental metastases than those with the p53 null expression pattern (87.8% vs. 64.7%, P=0.042). There were no statistically significant differences in median progression-free survival (PFS) (9 vs. 10 months, P=0.813) or median overall survival (OS) (12 vs. 17 months, P=0.526) between the two groups.; Conclusion: The prevalence of p53 mutations in HGSOC patients in this study was 93.6%. Omental metastasis is a significant pathological factor in predicting overexpression p53 pattern in HGSC. However, IHC analysis of the p53 staining pattern did not affect OS or PFS among patients with HGSOC.

Oracz, A., et al. (2023). "Brexanolone and current methods of treating postpartum and perinatal depression." Postepy Psychiatrii i Neurologii 39(1): 53-64.
	Objective. Postpartum depression (PPD) is estimated to affect between 6.5 and 12.9% of women who have given birth. If untreated, the disorder can lead to serious consequences for the patient and her offspring - compromising the formation of the relationship between mother and child. Drugs used to treat postpartum depression should be selected individually to achieve the best possible therapeutic effect, taking into account the severity of the depression, the risk of side effects and other factors determining the course of therapy. In our work, we compare selected treatments for PPD with an indication of the side effects associated with medication. The paper aims to evaluate brexanolone, a drug that is a synthetic form of the hormone allopregnanolone, a progesterone derivative, comparing it with the main pharmacological treatments for PPD, detailing the mechanisms of action of the above-mentioned groups of drugs and the side effects they induce. Literature review. The literature was reviewed in terms of the efficacy and safety of drugs used in PPD. Conclusions. Pharmacological treatment should be avoided if the patient's condition allows it. If necessary, SSRIs are the first choice drugs. If these are contraindicated, the use of TCAs may be considered, and in the most severe and resistant to treatment cases, the use of electroconvulsive therapy or a neurosteroid that acts on GABAergic conductivity of the CNS - allopregnanolone (as a drug, allopregnanolone is referred to as brexanolone). Sertraline appears to be the safest drug for women who are pregnant or in the postpartum period. An alternative to sertraline in lactating mothers is paroxetine or nortriptyline therapy. In our opinion, brexanolone will not replace SSRIs, due to the long duration of inpatient infusions and the indication for use only after delivery and not during pregnancy. It is important to bear in mind that this is a relatively new drug, so its action profile and potential side effects will only become apparent in future studies, so according to the current state of knowledge it should only be used when necessary.Copyright © 2023 Institute of Psychiatry and Neurology. All rights reserved.

Ordás, P., et al. (2022). "Comparison of surgical and obstetric outcomes in women with uterine leiomyomas after laparoscopic vs. abdominal myomectomy: A single-center cohort study." Frontiers in surgery 9: 997078.
	Our aim was to study the advantages, complications and obstetrical outcomes of laparoscopic myomectomy (LM) compared with abdominal myomectomy (AM). We conducted a retrospective cohort study at La Paz University Hospital that included LMs and AMs performed between 2012 and 2018, analyzing 254 myomectomies (142 AMs [55.7%] and 112 LMs [43.9%]). The mean number of fibroids was 1.8 ± 1.5 and 3 ± 2.9 for the LM and AM groups, respectively ( p < 0.006). The mean size of the largest myoma was 7.6 cm ± 2.7 cm and 10.2 cm ± 5.4 cm for the LM and AM groups, respectively ( p < 0.001). LMs were associated with longer surgical times ( p < 0.001) and shorter hospitalizations ( p = 0.001). There were no significant differences in the intraoperative and postoperative complication rates ( p = 0.075 and p = 0.285 for LM and AM, respectively). The subsequent pregnancy rate was higher for the LM group (30.8% vs. 16.8%, p = 0.009), with a vaginal delivery rate of 69% and no cases of uterine rupture.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2022 Ordás, Spagnolo, Fernández, Diestro Tejeda, Lafuente, Salas, Lopez Carrasco, Carbonell and Hernández.)

Ordaya Eloy, E., et al. (2023). "The Role of Novel Antifungals in the Management of Candidiasis: A Clinical Perspective." Mycopathologia 188(6): 937-948.
	Mucosal and invasive candidiasis can be challenging to treat in the setting of drug intolerance, antifungal resistance, drug-drug interactions, or host immune status. Antifungals with novel mechanisms of action and distinct pharmacokinetic/pharmacodynamic properties have been developed in recent years. Rezafungin is an echinocandin with high-tissue penetration and an extended half-life that allows for once-weekly administration, making it a convenient treatment option for invasive candidiasis while obviating the need for central catheter placement. Ibrexafungerp is an oral glucan synthase inhibitor that is active against most echinocandin-resistant Candida species. At present, it is approved for the treatment of acute vulvovaginal candidiasis and is under investigation as an oral step-down therapy following initial treatment with an echinocandin for cases of invasive candidiasis. Oteseconazole is a long-acting tetrazole that exhibits a higher affinity for the fungal enzyme CYP51, resulting in a potentially lower risk of drug-drug interactions and side effects compared to other azoles. It is currently approved for the treatment of recurrent vulvovaginal candidiasis. Fosmanogepix has a novel mechanism of action and potent activity against several Candida strains resistant to other antifungals. Due to its considerable bioavailability and tissue penetration, it holds promise as a potential treatment option in patients with invasive candidiasis, including those with chorioretinitis or meningitis. Results from clinical trials and observational studies will further delineate the role of these agents in the management of candidiasis. As the usage of these novel antifungals becomes widespread, we expect to acquire a greater understanding of their efficacy and potential benefits. (© 2023. The Author(s).)

O'Regan, E., et al. (2023). "Lymphovascular invasion plays a pivotal role in Endometrial cancer prognosis." Virchows Archiv 483(Supplement 1): S265.
	Background & objectives: The morbidity and mortality associated with endometrial cancer (EC) has increased in past decades despite diagnostic progress. We aim to analyse a vast panel of genes on their potential involvement in the genesis of endometrial cancer in the Polish Population. Method(s): A total of one hundred and three white female patients with confirmed EC were enrolled in the study. To align tumour staging each patient case was re-diagnosed according to the Eight Edition of the TNM Classification and the recent ESMO Clinical practice guidelines for diagnosis, Treatment and follow-up. All participants underwent surgical treatment without previous radio-chemotherapy to conduct a credible comparative analysis. Result(s): LVI had the strongest impact on OS. With regards to a correlation between LVI and targeted gene panel the mutations are as follows. PTEN 49%,PIK3CA 35%,KRAS 25%, TP53%, FGFR-2 14%, CTNNB1 12%, FBXW7 9%, ATM 1%, ALK1% and APC1%. Lymphovascular invasion was more commonly observed in TP53 mutated tumours ( R=0.3138,p=0.009). This was most often seen with EMT. The opposite results were seen in FGFR-2 mutation. Our results unanimously confirm, that the EMT features are useful for prediction but only LVI reached the predictive validity in the multivariant Cox model. The approach to explain the LVI mechanism led us to TP53 pathway, However the FGFR2 mutation in this field is unclear. Conclusion(s): Our Study confirmed EMT would be a reliable biomarker for the prediction of EC outcomes. FGFR-2 mutation could contribute to EMT and indirectly worsen it.FGFR-2 plays an important role in cancer progress even if via epithelial-mesenchymal transition. It seems that the original TCGA rules should be replaced with new ones. Future plans are for a control group and analysis of POLE gene. This involved longterm observation use of modern genetic testing methods. Our Results show other driving mutations to compare with the recommended panel.

Orellana, T. J., et al. (2023). "The role of adjuvant treatment for early-stage uterine clear cell carcinomas." Gynecologic Oncology 170: 77-83.
	Background: Uterine clear cell carcinoma is a rare and aggressive subtype of endometrial carcinoma. Prospective clinical trials have not been feasible for this rare tumor, and data regarding the optimal adjuvant treatment regimen for early-stage uterine clear cell carcinomas is limited. Our study's objective was to determine if adjuvant chemotherapy or radiation therapy improves patients' outcomes in stage I and II uterine clear cell carcinoma.; Methods: Patients with stage I and II uterine clear cell carcinoma were identified at a single institution. All cases were reviewed by a gynecologic pathologist. Both pure and mixed non-serous uterine clear cell carcinomas were included. Primary outcomes were recurrence free survival and overall survival.; Results: A total of 71 patients were identified including 39 (55%) pure and 32 (45%) mixed clear cell carcinoma. Most patients were FIGO stage IA (77.5%). Most patients (n = 58, 82%) received adjuvant therapy, including 43 (61%) receiving chemotherapy, 50 (70%) receiving radiation therapy, and 35 (49%) receiving both. Recurrence free survival was not significantly different among patients receiving no or <6 cycles of chemotherapy versus patients receiving 6 cycles of chemotherapy (p = 0.39). However, median OS was significantly different among patients receiving no or <6 cycles of chemotherapy versus 6 cycles of chemotherapy (p = 0.004). On univariable analysis, 6 cycles of chemotherapy was significantly associated with improved OS (HR 0.1, 95% CI 0.01-0.07). Presence of LVSI, mutated p53, number of pelvic and para-aortic lymph nodes assessed, adjuvant chemotherapy (any number of cycles), and >2 medical co-morbidities were not significant predictors of OS on univariable analysis. On multivariable analysis, 6 cycles of adjuvant chemotherapy remained a significant predictor of improved OS (HR 0.1, 95% CI 0.01-0.8).; Conclusions: In this study, administration of 6 cycles of chemotherapy appears to significantly improve OS. This finding suggests consideration of 6 cycles of adjuvant chemotherapy in patients with early-stage uterine clear cell carcinoma, however clinical trials are needed to confirm these findings.; Competing Interests: Declaration of Competing Interest Dr. Beriwal is a consultant for Elsevier Pathway and a member of the Data Safety Monitoring Board for Xoft. Dr. Beriwal was a faculty member in the Department of Radiation Oncology at the University of Pittsburgh Medical Center at the time that this project was conceived and conducted; he is now employed at Varian Medical Systems and Allegheny Health Network. Dr. Buckanovich is a cofounder of Tradewinds Bioscience. Dr. Bhargava has served as a consultant for Agilent Technologies, Inc. and ImmunoGen. Otherwise, the authors have no relevant conflicts of interest to disclose. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Orellana, T. J., et al. (2022). "Cost-Effectiveness Analysis of Tumor Molecular Classification in High-Risk Early-Stage Endometrial Cancer." Obstetrical and Gynecological Survey 77(4): 214-216.
	(Abstracted from Gynecol Oncol 2022;164:129–135) Endometrial cancer (EC) remains the most common gynecologic cancer in the United States, accounting for nearly 13,000 deaths in 2020 alone. Surgery remains the mainstay of treatment for early-stage EC; however, adjuvant treatment is often indicated.

Orellana, T. J., et al. (2022). "Cost-effectiveness analysis of tumor molecular classification in high-risk early-stage endometrial cancer." Gynecologic Oncology 164(1): 129-135.
	Purpose: Tumor molecular analyses in endometrial cancer (EC) includes 4 distinct subtypes: (1) POLE-mutated, (2) mismatch repair protein (MMR) deficient, (3) p53 mutant, and (4) no specific molecular profile. Recently, a sub-analysis of PORTEC-3 demonstrated notable differences in treatment response between molecular classification (MC) groups. Cost of testing is one barrier to widespread adoption of MC. Therefore, we sought to determine the cost-effectiveness of MC in patients with stage I and II high-risk EC.; Methods: A Markov decision model was developed to compare tumor molecular classification (TMC) vs. no testing (NT). A healthcare payor's perspective and 5-year time horizon were used. Base case data were abstracted from PORTEC-3 and the molecular sub-analysis. Cost and utility data were derived from public databases, peer-reviewed literature, and expert input. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Sensitivity analyses were performed to test model robustness.; Results: When compared to NT, TMC was cost effective with an ICER of $25,578 per QALY gained; incremental cost was $1780 and incremental effectiveness was 0.070 QALYs. In one-way sensitivity analyses, results were most sensitive to the cost of POLE testing, but TMC remained cost-effective over all parameter ranges.; Conclusions: TMC in early-stage high-risk EC is cost-effective, and the model results were robust over a range of parameters. Given that MC can be used to guide adjuvant treatment decisions, these findings support adoption of TMC into routine practice.; Competing Interests: Declaration of Competing Interest Dr. Buckanovich is a co-founder for Tradewinds Biosciences. Dr. Beriwal is a consultant for Elsevier Pathway and a member of the Data Safety Monitoring Board for Xoft. Dr. Beriwal was a faculty member in the Department of Radiation Oncology at the University of Pittsburgh Medical Center at the time that this project was conceived and conducted; he is now employed at Varian Medical Systems. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Organon, et al. (2022). A Study to Investigate Efficacy and Safety of OG-6219 BID in 3 Dose Levels Compared With Placebo in Participants Aged 18 to 49 With Moderate to Severe Endometriosis-related Pain.
	No Results Available Drug: OG-6219|Drug: Placebo Change from first treatment cycle to last planned treatment cycle in the mean OPP (endometriosis-related overall pelvic pain) score. The OPP measures endometriosis-related pain using NRS with range 0 (no pain) to 10 (worst imaginable).|Safety and tolerability of OG-6219|Change from first treatment cycle to last planned treatment cycle in the mean DYS score|Change from first treatment cycle to last planned treatment cycle in the mean|Change from first treatment cycle to last planned treatment cycle in the mean dyspareunia score.|Change from first treatment cycle to remaining treatment cycles in the mean number of tablets of rescue medication for endometriosis-related pain (ERP) and in the proportion of days participant has used rescue medication for ERP.|Change in Patient Global Impression of Severity (PGI-S) Score from V4 to Phone Contact 1, V6, and V7.|Percentage of participants with any improvement on the Patient Global Impression of Change at second, third and last planned treatment cycle.|Change from first treatment cycle to last planned treatment cycle in the Endometriosis Health Profile-30 (EHP-30) Domain Scores.|Mean change from Visit 1 to Visit 7 in bone biomarker levels|Proportion of participants with clinical parameters of significance from Visit 1 to Visit 5, Visit 6, Visit 7, and Visit 8.|Mean change from first treatment cycle to second, third and fourth treatment cycles in the percentage of days with vaginal bleeding|ECG parameter changes at each of the four treatment cycle visits|Mean change from V1 to V7 in serum hormone levels|Serum hormone levels at V5 comparing each treatment group|Serum hormone levels at V7 comparing each treatment group|Plasma concentrations of OG-6219 and FOR-1011 at scheduled assessments using sparse PK sampling.|Cmax, for both OG-6219 and FOR-1011.|Tmax for both OG-6219 and FOR-1011|AucTAU for both OG-6219 and FOR-1011 Female Phase 2 380 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment OG-6219-P001 December 2024

Oride, T., et al. (2023). "Clinical trial assessing the safety of edoxaban with concomitant chemotherapy in patients with gynecological cancer-associated thrombosis (EGCAT study)." Thrombosis journal 21(1): 57.
	Background: Gynecological cancer is one of the highest risk factors for cancer-associated thrombosis (CAT). Although low-molecular-weight heparin (LMWH) is recommended as an anticoagulant for treating CAT, recent studies have shown that direct oral anticoagulants (DOACs) are an acceptable alternative. Patients with cancer require a series of chemotherapies concomitantly with DOAC administration; however, the extent to which these drugs influence DOAC blood concentrations is unknown. In this study, we measured the plasma concentration of edoxaban during chemotherapy for gynecological cancers to determine its safety.; Methods: Patients histologically diagnosed with ovarian or uterine corpus cancer and CAT were recruited after primary surgery and before the initiation of postoperative adjuvant chemotherapy, including paclitaxel. Patients were administered edoxaban (30 or 60 mg) orally for CAT. The plasma concentrations of edoxaban and active factor Xa were determined and their percentage change before and after chemotherapy was calculated. Additionally, blood coagulation tests were analyzed.; Results: Sixteen patients with gynecological cancer (12 with ovarian cancer and 4 with uterine corpus cancer) were enrolled. Among these, 15 samples were collected one day after chemotherapy initiation. During chemotherapy, the trough concentration of edoxaban changed from 17.6 ± 10.6 to 20.0 ± 15.6 ng/ml, and the mean percentage change in edoxaban concentration was 14.5%. Therefore, the trough concentrations of edoxaban, which represent excretion capacity, were not significantly increased by chemotherapy with paclitaxel. The area under the plasma edoxaban concentration-time curve and the active factor Xa concentration were also unaffected.; Conclusion: Patients with CAT and ovarian or uterine corpus cancer administered edoxaban orally showed no significant increase in the trough concentration of edoxaban while undergoing chemotherapy. This suggests the safety of edoxaban use during the treatment of gynecological cancers.; Trial Registration: EGCAT study; Japan Registry of Clinical Trials, jRCTs051190024. (© 2023. The Author(s).)

Orla, G. and B. Ann-Marie (2022). "Infant massage and maternal symptoms of depression in the postnatal period."
	
Orlando, M., et al. (2021). "Non-hysteroscopic Myomectomy and Fertility Outcomes: A Systematic Review." Journal of Minimally Invasive Gynecology 28(3): 598.
	Objective: To perform a systematic review of the literature to identify best practices for nonhysteroscopic myomectomy for women with myomas who desire future fertility. The focus areas included factors associated with conception and pregnancy outcomes after myomectomy, impact of surgical route (laparotomic, laparoscopic, and the incorporation of robot assistance), and preoperative findings and surgical techniques that have an impact on reproduction.; Data Sources: Librarian-led electronic searches of the Ovid MEDLINE, Ovid Embase, and Cochrane CENTRAL databases were performed from inception to February 2020. A targeted reference review was performed to update the original searches.; Methods of Study Selection: The participants were women of reproductive age with myomas who underwent myoma removal surgery through laparotomic or laparoscopic approaches. The fertility outcomes included markers for ovarian reserve, clinical pregnancy rates, and pregnancy outcomes. We performed quality assessment using National Institutes of Health Study Quality Assessment Tools and developed clinical recommendations graded according to the strength of the evidence.; Tabulation, Integration, and Results: The initial search identified 2163 studies, of which 51 met the inclusion criteria. These consisted of 11 studies that focused on the factors associated with conception or pregnancy outcomes after myomectomy, 10 studies that examined the route of nonhysteroscopic myomectomy, and 30 that were related to intraoperative techniques and findings. Overall, younger age, lower myoma number, and distortion of the endometrial cavity were associated with improved reproductive outcomes after myomectomy. The route of nonhysteroscopic myomectomy and intraoperative uterine artery occlusion did not significantly affect pregnancy rates or outcomes. Adhesion barriers present a possible target for further research.; Conclusion: This study provides insights into patient selection and intraoperative techniques for nonhysteroscopic myomectomy. Further research with well-designed clinical trials is needed to highlight the relationships between myoma characteristics (International Federation of Gynecology and Obstetrics type, location, and size) and reproductive outcomes. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Orlando, M. S., et al. (2022). "Perioperative Venous Thromboembolism in Patients Undergoing Hysterectomy for Fibroids: A Nationwide Sample." Journal of Minimally Invasive Gynecology 29(11 Supplement): S2-S3.
	Study Objective: Venous thromboembolism (VTE) occurs in 0.4-0.7% of benign hysterectomies. Pelvic vascular compression secondary to fibroids may represent a mechanism for elevated VTE risk. We aimed to evaluate the incidence and timing of VTE among women undergoing hysterectomy for fibroids and other benign indications. Design(s): Retrospective cohort. Setting(s): Vizient clinical database. Patients or Participants: Adult women without thrombophilias who underwent benign hysterectomy between January 2015-December 2021. Intervention(s): VTE included pulmonary embolism or deep venous thrombosis diagnosed during four time periods: 1) preoperative remote (6 weeks to 1 year before surgery), 2) preoperative acute (6 weeks before surgery), 3) perioperative (6 weeks after surgery), and 4) postoperative remote (6 weeks to 1 year after surgery). Demographics, comorbidities, surgical characteristics, and VTE rates were compared by surgical indication. Measurements and Main Results: A total of 439,705 patients were identified (248,744 with fibroids and 190,961 without), and 0.98% (4,293) experienced VTE during the study period. On univariate analysis, individuals with fibroids were more likely than those without fibroids to have VTE during the preoperative remote (0.27% vs 0.22%, p<0.001), preoperative acute (0.27% vs. 0.19%, p<0.001), and perioperative periods (0.39% vs. 0.32%, p<0.001). On multivariable logistic regression adjusting for demographics, comorbidities, uterine weight =250g, and VTE prophylaxis, the presence of fibroids was associated with increased odds of VTE in the preoperative acute period (aOR 1.29, 95% CI 1.13 - 1.49, p<0.001). In contrast, the presence of fibroids was associated with reduced odds of VTE in the postoperative remote period (aOR 0.87, 95% CI 0.78-0.96, p=0.008). Conclusion(s): In a nationwide database, patients with fibroids undergoing hysterectomy were more likely than those with other indications to have VTE diagnosed before surgery. VTE risk was not increased postoperatively and may reflect appropriate use of prophylactic VTE measures in this patient population.Copyright © 2022

Orlando, M. S., et al. (2022). "Perioperative outcomes in a nationwide sample of patients undergoing surgical treatment of ovarian endometriomas." Fertility and Sterility 117(2): 444-453.
	Objective: To evaluate the perioperative outcomes of premenopausal women undergoing cystectomy or oophorectomy for ovarian endometriomas (OMAs) and other benign neoplasms. Design(s): Retrospective cohort study. Setting(s): Clinical database containing information from 580 US hospitals. Patient(s): Women 18 to 50 years old who underwent ovarian cystectomy or oophorectomy for benign indications between 2010 and 2020. Intervention(s): We compared procedure route, length of hospital stay, and complication rates by surgical indication (OMA vs. other benign neoplasms) and surgical procedure (cystectomy vs. oophorectomy). Main Outcome Measure(s): Thirty-day perioperative adverse events following adnexal surgery, including conversion to laparotomy, blood transfusion, ileus, urinary tract injury, bowel injury, readmission, and death. Result(s): We identified 120,208 ovarian cystectomies (28,182 OMAs and 92,026 other indications) and 53,476 oophorectomies (8,622 OMAs and 44,854 other indications). During cystectomy, patients with OMAs more commonly experienced conversion to laparotomy (5.1% vs. 3.1%) and readmission (8.5% vs. 7.1%). For oophorectomies, patients with OMAs less frequently had minimally invasive surgery (55.8% vs. 64.8%) or outpatient procedures (33.8% vs. 41.8%). Urinary tract and bowel injuries were rare. Multivariable logistic regression demonstrated that the presence of OMA predicted composite complications during cystectomy (adjusted odds ratio [aOR] 1.23, 95% confidence interval [CI] 1.18-1.28) but not during oophorectomy (aOR 1.05, 95% CI 0.99-1.12). Patients with OMAs had 1.37 times the odds of a composite complication during oophorectomy than during cystectomy (95% CI 1.28-1.47). Conclusion(s): Patients undergoing ovarian cystectomy for OMAs had higher rates of perioperative adverse events than patients undergoing ovarian cystectomy for other benign neoplasms. Laparotomies were performed more often during oophorectomies for OMAs than for other benign indications.Copyright © 2021 American Society for Reproductive Medicine

Oro, A., et al. (2022). "Trajectories of perinatal depressive symptoms in mothers and fathers according to the severity of preterm birth." Journal of Reproductive and Infant Psychology 40(2): cxxx.
	Background The literature has widely recognised preterm birth as a risk factor for perinatal depression (PND), with consequences for parenting and child development. However, little is known about the impact of the severity of prematurity on the trajectories of PND in mothers and fathers. Aims and Objectives This study aimed at describing the trajectories of depressive symptoms across the first year postpartum, investigating whether they changed as a function of the severity of birth weight and of its interaction with parental role. Methods The sample included 177 parental couples differentiated in 38 parents of Extremely Low Birth Weight (ELBW), 56 of Very Low Birth Weight (VLBW) and 83 of Full Term (FT) infants. At 3 9 and 12 months postpartum (T1, T2, T3 respectively), all mothers and fathers completed the Edinburgh Postnatal Depression Scale (EPDS) for the assessment of depressive symptoms. Trajectories were modelled throughout Growth Curve Mixed Models. Results As a function of birth weight, ELBW parents showed higher EPDS scores at T1 and a higher rate of reduction of symptoms over time, compared to VLBW and FT parents. As a function of birth weight and parental role, ELBW mothers showed, compared to VLBW and FT groups, higher EPDS scores at T1 and a higher rate of decrease of symptoms over time, while ELBW fathers did not show any differences. No differences emerged between VLBW and FT groups. Interpretation/Discussion The findings suggest that, after a preterm birth, ELBW babies' parents are more at risk for PND, especially the ELBW mothers. This risk is higher in the first trimester compared to the rest of the year, where a general trend of decrease of PND is evident, suggesting a resilient attitude in mothers of more severe preterm babies. Conclusions Early interventions to treat for PND should be promoted according to the risk connected to the severity of preterm condition.

Oróstica Maria, L., et al. (2022). "Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS." International Journal of Molecular Sciences 23(7).
	Polycystic ovary syndrome (PCOS) is an endocrine/metabolic disorder associated with insulin resistance (IR) and obesity. Endometria from women with PCOS present failures in insulin action, glucose uptake and signaling of insulin-sensitizing molecules, such as adiponectin, with consequences for reproduction. Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood. This study addresses the MTF effect, as well as adiponectin agonist action, on levels of molecules associated with insulin and adiponectin signaling pathways in endometrial tissue and cells, as assessed by immunohistochemistry and immunocytochemistry, respectively. Endometrial tissues were obtained from women and divided into five groups: Normal Weight (control); Obesity + IR; Obesity + IR + PCOS; Obesity + IR + MTF; Obesity + IR + PCOS + MTF. Endometrial cells stimulated with TNFα (as obesity-marker) were also used to partially emulate an obesity environment. The results showed low levels of insulin/adiponectin signaling in the endometria from women with obesity, IR and PCOS compared with the control group. MTF re-established these levels, independently of PCOS. TNFα-associated molecules were elevated in pathologic endometria, whereas MTF diminished these levels. The low levels of insulin/adiponectin molecules in endometrial cells treated with TNFα were reverted by MTF, similar to what was observed in the case of the adiponectin agonist. Therefore, independently of PCOS, MTF can re-establish levels of molecules involved in insulin/adiponectin signaling in endometrial cells, suggesting an improvement in insulin action and reproductive failures observed in endometria from women with obesity/PCOS.

O'Rourke, K. (2022). "Cemiplimab shines for recurrent cervical cancer." Cancer 128(11): 2050-2051.
	
O'Rourke, K. (2022). "Pembrolizumab is effective for endometrial cancer." Cancer 128(10): 1886-1887.
	
Orr, B., et al. (2022). "Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity." Clinical cancer research : an official journal of the American Association for Cancer Research 28(10): 2038-2049.
	Purpose: Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC.; Patients and Methods: Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received intraperitoneal IFNα at 2, 6, and 18 million units (MU), respectively. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and intraperitoneal wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively.; Results: The P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 months, respectively. Longitudinal sampling of the peritoneal cavity via intraperitoneal washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 week.; Conclusions: The chemokine-modulating intraperitoneal-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial. See related commentary by Aranda et al., p. 1993. (©2022 American Association for Cancer Research.)

Orszulak, D., et al. (2024). "The effect of gonadoliberin analog treatment in precocious puberty on polycystic ovarian syndrome prevalence in adulthood." Frontiers in Endocrinology 15: 1314752.
	Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood.; Material and Methods: The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria.; Results: The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03).; Conclusions: GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Orszulak, Niziński, Bil, Gawlik, Ziora and Drosdzol-Cop.)

Ort, S., et al. (2023). "THE EFFECTS OF PILATES AND OPEN-LABEL PLACEBO ON SEVERE PRIMARY DYSMENORRHEA-A RANDOMIZED CONTROLLED PILOT STUDY." Psychosomatic Medicine 85(4): A28.
	Background: Menstrual pain is very common and can significantly affect women's daily lives. The aim of this randomized controlled pilot study was to explore the effectiveness and feasibility of Pilates training and open-label placebos (OLP) in women with severe primary dysmenorrhea. Method(s): 34 participants (23.8 +/- 2.7 SD years) were randomly assigned to a Pilates group (n=13), an OLP group (n=11), or a control group (n=10). Five patients dropped out (4 due to covid-19 infection, 1 due to hormone use). Over the course of one menstrual cycle, the Pilates group performed a 50-minute online workout twice a week, the OLP group knowingly took a placebo capsule twice a day, and the control group received no treatment. For 1.5 menstrual cycles participants kept an online diary with 11-item numeric rating scales for pain (minimum, maximum, average), expectations, and well-being. Before and after the intervention, they completed standardized questionnaires (DASS-12, SF-12) and collected saliva samples to determine prostaglandins PGF2alpha and PGE2. Physical activity (BSA), treatment expectations (TEX-Q), and belief processes (Credition Form) were also assessed. Result(s): The primary outcome parameter was the pre-post change in the composite score of minimum, maximum, and average period pain on the first three days of the menstrual cycles. Both the Pilates group (-3.3 +/- 3.9 SD) and the OLP group (-2.7 +/- 4.4 SD) showed a greater decrease in composite score compared with the control group (-0.4 +/- 2.9 SD); p-values were non-significant, while Cohen's d effect sizes were moderate to large (Pilates vs. control: p = 0.087, d = 0.83; OLP vs. control, p = 0.198, d = 0.6). Possible treatment effects vs. control at moderate effect sizes were also observed for depression scores, perceived stress, PGF2alpha, and PGE2 in the Pilates group and for physical quality of life and PGF2alpha in the OLP group. Both treatments were positively evaluated. Conclusion(s): The data provide preliminary evidence that Pilates and OLP may improve dysmenorrhea and accompanying inflammatory processes. Pilates could also have a positive impact on psychological well-being. Results of this pilot study are promising and warrant a large randomized controlled trial with a longer intervention period.

Ortega, C., et al. (2022). "INTERVAL DISEASE SURGERY BY ROBOTIC APPROACH IN OVARIAN CANCER." International Journal of Gynecological Cancer 32(Supplement 2): A324-A325.
	Introduction/Background Ovarian cancer is one of the most lethal gynecological malignancies. This is because early diagnosis is difficult, and it usually presents in advanced stages. In these cases, randomized controlled trials have indicated that neoadjuvant chemotherapy (NACT) followed by interval disease surgery (IDS) offers similar of oncological and survival outcomes than primary surgery, and tumor burden remains is the principal poor prognostic factor. Historically, the surgical approach for these patients was by an explorative laparotomy. The role of the minimal invasive surgery (MIS) remains unclear. Thus, the purpose of our study is to evaluate the application of robotic surgery. Methodology A cohort retrospective study with prospectively collected data was performed including patients with advanced ovarian cancer who underwent to NACT and presented a radiological and serological favourable response and was possible to perform an optimal cytoreduction (R0) by robotic surgery. Clinicopathological and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were collected and analized. We have compared this selected group of patients with a historical cohort that includes patients with similar response taxes who underwent to laparotomic surgery also obtaining an optimal cytoreduction. Results The study includes a total of 15 patients who performed a robotic surgery and 22 a laparotomic surgery. In the robotic surgery cohort, the DFS at 3 years was 60.0% (CI 95% 32.8-87.2%) and 9.1% (CI 95% 0-21.1%) in the laparotomic, although no statistically significant differences were found between them (Log-Rank test p 0.343). The OS at 3 years in the robotic surgery cohort was 92.0% (CI 95% 77.0- 100%) and in the laparotomy group 52.7% (CI 95% 31.1- 74.2%), also without significant differences (Log-Rank test p 0.225). Conclusion Our study demonstrate that robotics surgery could be considered as an alternative cytoreduction option without worst survival outcomes respect laparotomic approach in highly selected patients. (Figure Presented).

Ortega, M. V., et al. (2022). "Asynchronous telehealth visits for the treatment of overactive bladder." Menopause 29(6): 723-727.
	Objective:Overactive bladder affects 17% of women, and adherence to treatment is notoriously low. The objective of this pilot study is to investigate the efficacy and feasibility of the use of asynchronous telehealth visits for the treatment of women with overactive bladder. Method(s):This is a pilot study of women who participated in the asynchronous telehealth program with a new diagnosis of overactive bladder presenting to the Massachusetts General Hospital from January of 2020 to March of 2021. Pre-post differences in Urogenital Distress Inventory score-6, and Incontinence Severity Index Scores were compared with paired t tests as coprimary endpoints. To assess potential mechanisms of association between asynchronous visits and patient-reported outcomes, total fluid intake, caffeinated beverage consumption, urinary frequency, episodes of urinary leakage were also compared as secondary endpoints. Result(s):A total of 23 women participated, with 50 e-visits completed. The first asynchronous visit was completed after a median of 42days (IQR 36, 51.5) from the initial visit. There was a decrease in the Urogenital Distress Inventory-6 score between the first asynchronous visit and the last (29 points, IQR 16, 37 vs 12 points, IQR 12, 25), respectively (P=0.014). Similar findings were seen with the Incontinence Severity Index questionnaire, from three (IQR 2, 4) to three (IQR 1, 3) after the asynchronous visit (P=0.002). Conclusion(s):We demonstrate the feasibility of asynchronous visits for the treatment of overactive bladder. Although our results suggest efficacy, given the prepost change in overactive bladder-related questionnaire scores following asynchronous visits, the comparative effectiveness of asynchronous visits versus regular care needs to be confirmed in a randomized trial.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Ortiz, C. A., et al. (2022). "What is the ideal management of Krukenberg syndrome?" Journal of Surgical Case Reports 2022(7): rjac328.
	We present the case of a 34-year-old female patient diagnosed with Krukenberg Syndrome, in which we performed total cytoreduction surgery of the lesions, with subsequent perioperative chemotherapy. After a follow-up of three years, we observe she continues without evidence of disease. In the early 1990's Sugarbaker et al. introduced cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as a new innovative therapy option for selected patients with peritoneal carcinomatosis. Nowadays, there is no established treatment for patients with peritoneal metastasis of colorectal cancer. There is a need for the future high-quality randomized multicenter trials to make a strong recommendation.Copyright © 2022 Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved.

Ortiz, M., et al. (2023). "Clinical effects of Kneipp hydrotherapy: a systematic review of randomised controlled trials." BMJ Open 13(7): e070951.
	Objective: Hydrotherapy is a traditional prevention and treatment strategy. This study's aim is to systematically review all available randomised controlled trials (RCTs) investigating clinical effects of hydrotherapy according to Kneipp which is characterised by cold water applications.; Methods: RCTs on disease therapy and prevention with Kneipp hydrotherapy were included. Study participants were patients and healthy volunteers of all age groups. MEDLINE (via PubMed), Scopus, Central, CAMbase, and opengrey.eu were systematically searched through April 2021 without language restrictions and updated by searching PubMed until April 6th 2023. Risk of bias was assessed using the Cochrane tool version 1.ResultsTwenty RCTs (N=4247) were included. Due to high heterogeneity of the RCTs, no meta-analysis was performed. Risk of bias was rated as unclear in most of the domains. Of 132 comparisons, 46 showed significant positive effects in favour of hydrotherapy on chronic venous insufficiency, menopausal symptoms, fever, cognition, emotional function and sickness absenteeism. However, 81 comparisons showed no differences between groups and 5 were in favour of the respective control group. Only half of the studies reported safety issues.; Conclusion: Although RCTs on Kneipp hydrotherapy seem to show positive effects in some conditions and outcomes, it remains difficult to ascertain treatment effects due to the high risk of bias and heterogeneity of most of the considered studies. Further high-quality RCTs on Kneipp hydrotherapy are urgently warranted.; Prospero Registration Number: CRD42021237611.; Competing Interests: Competing interests: The authors MO, AKK, HC, GR, MT, HH and KL declare that they have no financial or other competing interests. BB was supported by the Kneipp Association in the context of his professorship at the Charité. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Orvieto, R., et al. (2022). "Elective egg freezing patients may benefit from increasing the maximal daily gonadotropin dose above 300IU." Reproductive Biology and Endocrinology 20(1): 171.
	Objective: Nowadays, patients attempting social/elective egg freezing has spread globally. Ovarian stimulation (OS) with high daily gonatotropin doses, are commonly offered to this group of patients, aiming to achieve the maximal oocytes cohort with minimum IVF cycle attempts. We aim to assess the IVF-ET outcome, and specifically the oocyte yield, of patients undergoing two successive IVF cycle attempts for elective egg freezing (EEF), and whether changing the daily gonadotropin dose in the second IVF cycle attempt, affect the outcome. Patients and Methods: All women admitted to our IVF unit for social/EEF, who underwent 2 consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300 IU were included. Ovarian stimulation characteristics, duration of OS, number of retrieved oocytes, number of mature oocytes were assessed and compared between the 1st and the 2nd IVF cycle attempts, and between the different daily gonadotropin doses and the oocyte yields in the 2nd cycle attempt (increase, decrease or no change). Main Outcome Measure(s): Oocytes and mature oocytes yield in the 2nd as compared to the 1st IVF cycle attempt. Result(s): A reduced oocyte yield in the 2nd cycle attempt was observed in those who highly responded in the 1st attempt, regardless the daily dose in the 2nd cycle attempt (whether it was increased, no change and decreased). Moreover, the proportion of patients with same or more oocytes in the 2nd IVF cycle attempt was significantly lower in patients with high peak E2 levels, compared to those with peak E2 levels < 9175 pmol/L. Among patients with high peak E2 (> 9175 pmol/L), those who achieved a lower oocytes yield in the 2nd IVF cycle attempt had lower basal Day-3 FSH/LH ratio (1.5 + 0.5 vs 1.8 + 0.8, p < 0.03) and higher oocyte (range: 7-28, median:10; vs range: 2-15, median:7) and mature oocytes yields. With a cut-off of 9 oocytes, 78.8% of those with > 9 oocytes and 61.8% of those with < 9 oocytes will achieve lower/higher oocytes yield in the 2nd IVF cycle attempt, respectively. Conclusion(s): Ovarian stimulation with high daily gonatotropin doses (300 IU) should be offered to patients attempting social/EEF. Moreover, in their 2nd IVF cycle attempt, those with high peak E2 (> 9175 pmol/L) in the 1st attempt, and basal Day-3 FSH/LH ratio < 1.5 and/or more than 9 oocytes retrieved, should receive same OS protocol with no change in the daily gonadotropin dose.Copyright © 2022, The Author(s).

Osada, H., et al. (2023). "Prevalence of chronic endometritis in patients with infertility due to hydrosalpinx or pelvic peritubal adhesions and effect of laparoscopic surgical correction on pregnancy rates post in vitro fertilization." European Journal of Obstetrics, Gynecology, and Reproductive Biology 284: 143-149.
	Objective(s): To assess the prevalence of chronic endometritis (CE) in patients with infertility and hydrosalpinx or peritubal adhesions and to examine the effects of laparoscopic surgical correction (LSC) on CE and pregnancy rates post in vitro fertilization and embryo transfer (IVF-ET).; Study Design: This is a retrospective cohort study at private IVF-ET centers. A total of 438 patients, known to have hydrosalpinx (n = 194) or peritubal adhesions (n = 244), and undergoing IVF treatment between April 1, 2018 and September 30, 2020 were included in the study. Hysterosalpingography, magnetic resonance imaging, and transvaginal ultrasonography were used to diagnose the hydrosalpinx or peritubal adhesions. Laparoscopic examination and surgical correction were performed on patients with CE. IVF-ET was performed after recovery from LSC.; Results: CE was present in 45.9% of patients (89/194) with hydrosalpinx and 14.3% with peritubal adhesions (35/244). All the 89 patients with CE and hydrosalpinx underwent laparoscopic salpingostomy and/or fimbrioplasty, and 64 (71.9%) further underwent proximal tubal occlusion. All the 35 patients with CE and peritubal adhesions underwent laparoscopic adhesiolysis and/or fimbrioplasty, and 19 (54.3%) further underwent proximal tubal occlusion. CD138 PC levels after LSC decreased to < 5 in 70 of 124 patients (56.5%) in one menstrual cycle and decreased to < 5 in all cases within 6 months. Of the 66 patients who underwent a single blastocyst transfer, 57 delivered (cumulative live birth rate (LBR): 86.3%). The cumulative LBR of patients treated for CE with LSC (86.3%) was significantly different from those given antibiotic therapy (320 patients; 38.4%; p <.0001) and the CD138-negative groups (811; 31.8%; p <.0001).; Conclusion: CE is prevalent in patients with hydrosalpinx and/or peritubal adhesions who present with infertility. LSC improved CE without antibiotic therapy, improving the CP and LBR after IVF-ET.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Osborn, G., et al. (2023). "IgE antibody engagement and activation of human monocyte and macrophage subsets for cancer immunotherapy." Allergy: European Journal of Allergy and Clinical Immunology 78(Supplement 111): 614.
	Background: Ovarian cancer has the highest mortality rate among gynaecological cancers. Tumour-associated macrophages (TAMs) contribute extensively to this poor prognosis, especially through polarisation to immunosuppressive subsets to inhibit anti-tumour immunity. Tumour-specific monoclonal antibodies (mAbs) offer the ability to bi-specifically engage tumours and TAMs. Conventional IgG-class mAbs have however performed poorly in ovarian cancer patients. MOv18 IgE, which targets tumour antigen folate receptor alpha (FRa), is the first IgE-class mAb to enter clinical testing (NCT02546921). IgE offers potential anti-tumoural advantages compared to IgG, including higher receptor affinity and tissue half-life and a lack of inhibitory receptor. Method(s): A panel of macrophage subsets were derived from healthy volunteers to model the phenotypic heterogeneity of ovarian TAMs. Moreover, TAMs were isolated from patient ascites. Flow cytometry was used to measure levels of macrophage-mediated antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) of tumour cells in response to tumour-specific IgE and IgG1 mAbs. Macrophage-bound IgE was crosslinked ex vivo by anti-IgE p olyclonal antibodies and the polarisation effect assessed by flow cytometry and Luminex. Result(s): Here we show that tumour-specific IgE mAbs have a unique two-arm macrophage-mediated anti-tumoural mechanism. Firstly, IgE mAbs induced tumour killing by both immunostimulatory M1 and immunosuppressive M2-associated macrophage subsets. IgE-mediated killing was superior to the IgG1 equivalent due to enhanced antibody-dependent cellular cytotoxicity (ADCC). Secondly, IgE stimulation induce an immunostimulatory polarisation of both M2-associated macrophages, as well as patient TAMs. In contrast, M1 macrophages maintained their immunostimulatory phenotype. High tumour expression of the identified IgE polarisation signature was associated with improved survival in ovarian cancer patients. Conclusion(s): IgE mAbs induce a unique activation of a heterogenous macrophage population which could promote a clinically relevant immune shift in ovarian cancer away from pro-tumuoral immunosuppression towards anti-tumoural immunostimulation.

Osborn, G., et al. (2022). "Macrophages in ovarian cancer and their interactions with monoclonal antibody therapies." Clinical and experimental immunology 209(1): 4-21.
	The unmet clinical need for effective treatments in ovarian cancer has yet to be addressed using monoclonal antibodies (mAbs), which have largely failed to overcome tumour-associated immunosuppression, restrict cancer growth, and significantly improve survival. In recent years, experimental mAb design has moved away from solely targeting ovarian tumours and instead sought to modulate the wider tumour microenvironment (TME). Tumour-associated macrophages (TAMs) may represent an attractive therapeutic target for mAbs in ovarian cancer due to their high abundance and close proximity to tumour cells and their active involvement in facilitating several pro-tumoural processes. Moreover, the expression of several antibody crystallisable fragment (Fc) receptors and broad phenotypic plasticity of TAMs provide opportunities to modulate TAM polarisation using mAbs to promote anti-tumoural phenotypes. In this review, we discuss the role of TAMs in ovarian cancer TME and the emerging strategies to target the contributions of these cells in tumour progression through the rationale design of mAbs. (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Immunology.)

Osborne, L. A., et al. (2022). "Cluster randomised control trial of the effect on attendance and outcomes of multi-disciplinary teams involving psychologists during pelvic floor muscle training for pelvic floor dysfunction." Journal of Obstetrics and Gynaecology 42(2): 310-315.
	Pelvic floor muscle training (PFMT) is effective, acceptable to patients, and cost efficient as a treatment for Pelvic Floor Dysfunction (PFD). However, PFMT outcomes are mediated by patient variables, such as depression, anxiety, motivation, and health values. The current study examined whether multi-disciplinary provision of PFMT involving a psychologist would improve attendance and outcomes (Clinical Trial Registration: NCT02549157). 88 consecutively referred patients (age 28 - 85 years), with a variety of PFD, were randomised into two groups: PFMT treatment as usual (n = 47), and PFMT with a psychologist involved (n = 41). Patients received 6-month out-patient physiotherapy. More patients with the psychologist completed the course, and there were significantly greater improvements in subjective symptoms (Queensland scale), quality of life (EQ-5D), and anxiety (HADS), although not in objective measures (Oxford Grading) or depression (HADS). These results suggest that an MDT including a psychologist during PFMT intervention treatment may help some patients.IMPACT STATEMENTWhat is already known on this subject? Pelvic floor muscle training (PFMT) is effective, acceptable to patients, and cost efficient as a treatment for Pelvic Floor Dysfunction (PFD). However, PFMT outcomes are mediated by patient variables, such as depression, anxiety, motivation, and health values. The effectiveness of a multi-disciplinary team delivering both PFMT and psychological support simultaneously to women undergoing PFMT for PFD is unknown. What do the results of this study add? Psychological support delivered alongside PFMT increased patient attendance, improved subjective ratings of pelvic floor functioning, health-related quality of life, and reduced anxiety. This is one of the first demonstrations that this can be achieved through a multi-disciplinary team delivering their support simultaneously to the patients. What are the implications of these findings for clinical practice and/or further research? Improving subjective functioning and reducing attrition rates in PFD patients has cost implications in terms of reduced need for surgery, and making future surgery more effective. The inclusion of brief, easily delivered psychological support, integrated into the PFMT sessions in a multidisciplinary way may represent an extremely cost effective method of improving the service for these patients.Copyright © 2021 Informa UK Limited, trading as Taylor & Francis Group.

O'Shea, M., et al. (2023). "Standard Restrictions vs Expedited Activity After Pelvic Organ Prolapse Surgery: A Randomized Clinical Trial." JAMA Surgery 158(8): 797-805.
	Importance: Restrictions on postoperative activity following pelvic organ prolapse (POP) surgery are not evidence based. Nonetheless, many pelvic surgeons place lifting and activity restrictions on patients following surgery.; Objective: To evaluate whether expedited activity results in noninferior anatomic and symptomatic outcomes compared with standard activity restrictions after POP surgery.; Design, Setting, and Participants: This randomized noninferiority clinical trial included patients undergoing vaginal or laparoscopic apical reconstructive surgery for POP between July 1, 2020, and October 31, 2021, at a single academic tertiary referral center in Durham, North Carolina. Anatomic outcomes were assessed by masked examiners, and subjective outcomes were assessed via validated surveys, both completed at 3 months postoperatively. Patients meeting minimum physical activity criteria with at least stage II bothersome POP were eligible. A total of 218 patients were approached, of whom 123 were randomly assigned and 107 had complete outcome data and were included in the analysis.; Interventions: Patients were randomly assigned to receive standard restrictions vs expedited postoperative activity instructions.; Main Outcomes and Measures: The anatomic coprimary outcome was maximum anatomic POP support loss (SLmax), which is the most distal point of pelvic organ support loss according to the Pelvic Organ Prolapse Quantification System (noninferiority margin, 1.0 cm). The symptomatic coprimary outcome was the Pelvic Organ Prolapse Distress Inventory (POPDI) symptom score (noninferiority margin, 34.3 points). Differences between outcomes were assessed using linear regression models controlling for baseline SLmax and POPDI, respectively.; Results: Of 123 participants randomized, 107 had complete 3-month outcome data and were included in the analysis. Mean (SD) age was 62.8 (10.1) years. At 3 months, mean (SD) SLmax was -1.7 (1.4) cm in the expedited group and -1.5 (1.4) cm in the standard group (P = .44). After adjusting for baseline SLmax, the mean maximum support loss was 0.18 cm higher within the vaginal canal in the expedited group (95% CI, -0.68 to 0.33 cm). The coprimary outcome of POPDI score was a mean (SD) 23.7 (41.8) points in the expedited group vs 25.7 (39.3) points in the standard group (P = .80). After adjusting for baseline scores, mean POPDI scores were 5.79 points lower in the expedited group (95% CI, -20.41 to 8.84).; Conclusions and Relevance: The findings demonstrate that expedited activity after prolapse surgery results in noninferior anatomic and symptomatic prolapse outcomes. It is reasonable to instruct patients undergoing minimally invasive prolapse surgery to resume physical activities ad lib postoperatively.; Trial Registration: ClinicalTrials.gov Identifier: NCT04329715.

Osman, M. A. A., et al. (2022). "Surgicel for Prevention of Postoperative Adhesions in Laparoscopic Myomectomy: A Propensity Score-Matching Analysis." Journal of Gynecologic Surgery 38(2): 111-114.
	Objective: Postoperative adhesions after laparoscopic myomectomy (LM) are a significant clinical problem. Use of adhesion barriers was suggested as a preventive measure. The present study was conducted to assess the role of intraoperative oxidized regenerated cellulose (Surgicel; Ethicon USA) for preventing postoperative adhesions in women undergoing LM. Material(s) and Method(s): The study included 114 women with previous LM who underwent various kinds of open and laparoscopic surgeries after LM. The study included 57 patients who agreed to use the surgical-Adhesions barrier (a Surgicel group) and 57 patients who did not use the adhesion barrier product (control group). To reduce bias related to unbalanced patients' selection, a propensity score-matching analysis was performed. Result(s): Comparison between the 2 groups regarding frequency of adhesions revealed a significantly lower frequency of adhesions in the Surgicel group (12.3% versus 31.6%; p = 0.013). Comparison between the groups regarding the type of adhesions showed a higher frequency of filmy adhesions in the Surgicel group. However, the difference was not statistically significant. Logistic regression analysis identified previous cesarean section (odds ratio [OR]: 0.16; confidence interval [CI]: 0.06-0.45; p = 0.001) and lack of Surgicel use (OR: 0.28; CI: 0.1-0.78; p = 0.015) as significant predictors of postoperative adhesions development. Conclusion(s): The present study suggests that use of Surgicel adhesion barrier with LM is associated with lower frequency and severity of postoperative adhesions. (J GYNECOL SURG 38:111)© Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.

Osmanlıoğlu, Ş., et al. (2023). "Presence of Endometrioma Does Not Impair Embryo Quality and Assisted Reproductive Technology (ART) Cycle Outcome in Diminished Ovarian Reserve (DOR) Patients." Reproductive sciences (Thousand Oaks, Calif.) 30(5): 1540-1547.
	This study aims to assess the impact of endometrioma on embryo quality and cycle outcome in patients who undergo assisted reproductive technology (ART) treatment due to diminished ovarian reserve (DOR). Retrospective case-control study was conducted in women ≤ 40 years of age who underwent ART treatment caused by DOR, defined according to POSEIDON criteria, at a university-based infertility clinic between January 2015 and December 2020. Three groups of patients were selected: group A included patients with an idiopathic DOR, group B included patients with endometrioma(s) who underwent ovarian cystectomy, and group C included patients with endometrioma(s) without surgical treatment. A total of 351 women with DOR were included in the final analysis. Demographic characteristics, including age and AMH, were similar between the groups. Significant differences were observed among groups on mean number of MII oocytes retrieved (1.88 ± 1.59 vs. 2.84 ± 2.89 vs. 2.78 ± 2.41, respectively; p < 0.001) and mean number of embryos (1.04 ± 1.18 vs. 1.87 ± 2.01 vs. 1.66 ± 1.81, respectively; p < 0.001). However, the mean number of top-quality embryos, cycle cancellation, and live birth rates were similar between the groups. Clinical pregnancy (35 (26.5%) vs. 8 (18.2%) vs. 18 (42.9%), respectively; p = 0.038) and miscarriage rates (12 (9.1%) vs. 0 vs. 8 (19.0%), respectively; p = 0.009) were higher in endometrioma group without surgery. Women with DOR appear to have similar ART cycle outcomes regardless of the etiology, in terms of live birth rates. Infertility of endometrioma patients might be related to altered endometrium rather than to decreased oocyte quality. Cystectomy for endometrioma before IVF did not seem to affect the LBR. (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Osse, N. J. E., et al. (2023). "Comparing Single-Incision Midurethral Sling with Bulking Agents for Female Stress Urinary Incontinence: Rationale for a Non-Randomized Controlled Trial." Gynecologic and Obstetric Investigation 88(2): 123-131.
	Objectives: Midurethral slings are considered the gold standard for the surgical treatment of stress urinary incontinence (SUI), with an efficacy up to 80%. Another therapeutic option is the use of bulking agents, which create an artificial mass in the urethral submucosa, with an efficacy varying from 64% to 74%. Although bulking agents have a lower risk of complications than midurethral sling surgery, they are mainly used in case a midurethral sling is not an option or if midurethral sling surgery failed to cure stress urinary incontinence. In this study, we offer all patients with SUI in secondary care a choice between a single-incision midurethral sling procedure and treatment with a bulking agent. We want to examine patient preference and patient satisfaction for both procedures. We expect that offering both interventions in combination with standardized counselling will result in high patient satisfaction. Design(s): In this non-randomized controlled trial, 266 patients will be objectively counselled for both interventions, after which all patients will choose between single-incision midurethral slings and polyacrylamide hydrogel (PAHG), followed by the standard care procedure for women with SUI. Participants/Materials, Setting, Methods: From January 1, 2021, onward, all consecutive adult patients (between 18 and 80 years of age) attending the outpatient gynaecology department with objectively confirmed, moderate to severe SUI will be eligible for enrolment in this non-randomized study. The primary outcome is patient satisfaction at 1 year, measured by the Patient Global Impression of Improvement; secondary outcomes are patient satisfaction at 3 months, objective and subjective cure at 3 months and 1 year, adverse events, post-operative pain, and cost-effectiveness. Differences in outcome measures will be assessed through logistic and linear regression analyses, both unadjusted and adjusted with covariate adjustment using the propensity score. Result(s): No results are available yet. Limitation(s): The major disadvantage of this study design is the potential confounding bias. We intend to eliminate this bias by applying propensity scoring. Conclusion(s): By designing a non-randomized patient preference trial, we not only expect to demonstrate high patient satisfaction with both interventions but also provide insight into the possible role of PAHG-injections in the treatment of female SUI as a first-choice non-conservative treatment.Copyright © 2023 The Author(s). Published by S. Karger AG, Basel.

Ostadi, A., et al. (2023). "Therapeutic effect of turmeric on radiodermatitis: A systematic review." Physiological reports 11(5): e15624.
	Radiodermatitis (RD) occurs in 95% of cancer patients undergoing radiation therapy. At present, there is no effective treatment for the management of this complication of radiotherapy. Turmeric (Curcuma longa) is a polyphenolic and biologically active natural compound with various pharmacological functions. The aim of this systematic review was to determine the efficacy of curcumin supplementation for reducing RD severity. This review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive literature search was conducted in Cochrane library, PubMed, Scopus, Web of Science, and MEDLINE databases. A total of seven studies comprising 473 cases and 552 controls were included in this review. Four studies demonstrated that curcumin supplementation had a beneficial effect on RD intensity. These data provide evidence for the potential clinical use of curcumin in supportive cancer care. Further large prospective and well-designed trials are warranted to exactly determine the "real effective extract, supplemental form and dose of curcumin" for RD prevention and treatment of patients receiving radiotherapy.Copyright © 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Ostermann, T., et al. (2020). "A Systematic Review and Meta-Analysis on the Survival of Cancer Patients Treated with a Fermented Viscum album L. Extract (Iscador): An Update of Findings." Complementary Medicine Research 27(4): 260-271.
	Purpose: We aimed at updating the evidence found in controlled studies addressing general and event-free survival of cancer patients treated with the fermented mistletoe extract Iscador.; Methods: The databases Embase, PubMed, CAMbase, Scopus, AMED and Cochrane were searched for clinical studies on cancer patients treated with Iscador. Quality of studies and risk of bias were evaluated according to the Cochrane guidelines and the Newcastle Ottawa Scale. Outcome data were expressed as hazard ratios (HR) and the respective 95% confidence intervals (CI). Meta-analysis was carried out using a random-effects model.; Results: Eighty-two controlled studies met the inclusion criteria, of which 32 with 55 strata provided data for extracting HR and CI. The overall HR was 0.59 (95% CI: [0.53; 0.65], p < 0.0001) in favour of Iscador treatment. Heterogeneity of study results was moderate (I2 = 50.9%; p < 0.0001, τ2 = 0.053). Meta-regression did not reveal significant effects of sample size or study design. However, significant differences were found between cancer entities (p < 0.01), with most pronounced effects in cervical (HR = 0.43) and less pronounced effects in lung cancer (HR = 0.84).; Conclusions: We found almost identical effects on cancer survival based on a broader database of higher quality. However, none of the studies was blinded and, therefore, there might be risk of performance bias. Implications for cancer survivors are as follows: findings indicate that adjuvant treatment of cancer patients with Iscador can be associated with a better survival. (The Author(s). Published by S. Karger AG, Basel.)

Ostlund, T., et al. (2022). "Triazole-estradiol analogs: A potential cancer therapeutic targeting ovarian and colorectal cancer." Steroids 177: 108950.
	1,2,3-triazoles have continuously shown effectiveness as biologically active systems towards various cancers, and when used in combination with steroid skeletons as a carrier, which can act as a drug delivery system, allows for a creation of a novel set of analogs that may be useful as a pharmacophore leading to a potential treatment option for cancer. A common molecular target for cancer inhibition is that of the Epidermal Growth Factor Receptor/Mitogen Activated Protein Kinase pathways, as inhibition of these proteins is associated with a decrease in cell viability. Estradiol-Triazole analogs were thus designed using a molecular modeling approach. Thirteen of the high scoring analogs were then synthesized and tested in-vitro on an ovarian cancer cell line (A2780) and colorectal cancer cell line (HT-29). The most active compound, Fz25, shows low micromolar activity in both the ovarian (15.29 ± 2.19 µM) and colorectal lines (15.98 ± 0.39 µM). Mechanism of action studies proved that Fz25 moderately arrests cells in the G1 phase of the cell cycle, specifically inhibiting STAT3 in both cell lines. Additionally, Fz57 shows activity in the colorectal line (24.19 ± 1.37 µM). Inhibition studies in both cell lines show inhibition against various proteins in the EGFR pathway, namely EGFR, STAT3, ERK, and mTOR. To further study their effects as therapeutics, Fz25 and Fz57 were studied against drug efflux proteins, which are associated with drug resistance, and were found to inhibit the ABC transporter P-glycoprotein. We can conclude that these estradiol-triazole analogs provide a key for future studies targeting protein inhibition and drug resistance in cancer. (Copyright © 2021. Published by Elsevier Inc.)

Osuga, Y., et al. (2021). "Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in women with endometriosis-associated pain: phase 2 safety and efficacy 24-week results." BMC Women's Health 21(1): 250.
	BACKGROUND: Relugolix is a once-daily, oral, nonpeptide, gonadotropin-releasing hormone receptor antagonist. The aim of this study was to evaluate safety of relugolix over 24 weeks in women with endometriosis-associated pain. METHODS: This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan. Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks. Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks. The primary outcome was safety, including bone mineral density (BMD) and treatment-emergent adverse events (TEAEs). Secondary endpoints included visual analog scale (VAS) scores for endometriosis-associated pain. Analysis sets were defined as all patients who were administered the study drug. RESULTS: Of 487 randomized patients in the preceding study, 397 enrolled in this extension study and continued to receive placebo (n = 77), relugolix 10 mg (n = 84), relugolix 20 mg (n = 78), relugolix 40 mg (n = 89), or leuprorelin (n = 69). Baseline characteristics were similar between extension study patients and patients in the preceding study. Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups. Mean (SD) change in BMD from baseline at Week 24 was - 0.2 (1.99)% for placebo; - 1.6 (2.34)%, - 2.6 (2.94)%, and - 4.9 (2.91)% for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 4.4 (2.16)% for leuprorelin. Mean ± SD change from baseline in mean VAS score (mm) for pelvic pain at end of treatment was - 3.2 ± 12.16 for placebo; - 6.8 ± 10.56, - 9.0 ± 11.84, and - 11.9 ± 11.26 for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 12.7 ± 12.57 for leuprorelin. Estradiol levels decreased with increasing relugolix dose and remained below postmenopausal levels throughout the 24-week relugolix 40-mg treatment period. CONCLUSIONS: Treatment with relugolix for 24 weeks was generally well tolerated and demonstrated similar pain reduction to leuprorelin in women with endometriosis. The dose-dependent loss in BMD observed with relugolix treatment was expected due to an induced hypoestrogenic state. Relugolix demonstrated a similar benefit/risk profile to injectable therapy in this phase 2 study. Trial registration NCT01452685 (ClinicalTrials.gov, registered 17/10/2011).

Otake, A., et al. (2022). "Comparative Study of Postoperative Analgesic Effects of Intraoperative Levobupivacaine Local Infiltration Anesthesia and Transversus Abdominis Plane Block Following Gynecologic Laparoscopy." Gynecology and Minimally Invasive Therapy 11(4): 231-237.
	Objectives: We aim to assess the postoperative analgesic effect of intraoperative levobupivacaine local infiltration anesthesia (LA) and transversus abdominis plane (TAP) block in gynecologic laparoscopy.; Materials and Methods: We conducted a retrospective analysis on the data of 260 patients treated by gynecologic laparoscopy (adnexal surgery, hysterectomy, and myomectomy) between January 2019 and December 2020 at Minoh City Hospital, Osaka Japan. Patients were divided into two groups: intraoperative LA group and TAP block group. We assessed clinical characteristics, surgical results, postoperative numerical rating scale (NRS) pain scores, and the frequency of analgesic use up to 24 h after surgery in overall and by each type of surgery. Pearson's χ 2 test, Fisher's exact test, and Wilcoxon/Kruskal-Wallis test were used for statistical analysis. Multiple regression analysis was used for multivariate analysis.; Results: NRS pain score was statistically significantly higher in the LA group than in the TAP group 1 h after surgery in overall ( P = 0.04), with NRS difference of 0.4 which was not clinically significant. No significant differences were observed in NRS pain scores at 3, 6, 12, and 24 h after surgery or in the frequency of analgesic use up to 24 h after surgery in overall and by type of surgery. Endometriosis was associated with increased postoperative pain at 1 h after surgery in adnexal surgeries ( P = 0.04) and suggestive for all surgeries. Younger age was related to more frequency of analgesic use up to 24 h after surgery in overall, adnexal surgeries, and hysterectomy.; Conclusion: Intraoperative levobupivacaine LA may have similar postoperative analgesic effects as TAP block in gynecologic laparoscopy.; Competing Interests: Akiko Otake, Naoko Sasamoto, Noriko Sato, Ryota Kumasaka, Yoshimitsu Yamamoto, and Kazushige Adachi complied with the journal's Conflict of Interest Policy. (Copyright: © 2022 Gynecology and Minimally Invasive Therapy.)

Otani-Matsuura, A., et al. (2022). "Depression symptoms during pregnancy and postpartum in patients with recurrent pregnancy loss and infertility: The Japan environment and children's study." Journal of Reproductive Immunology 152: 103659.
	There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary.

Otgontuya, A., et al. (2022). "Comparison of the Clinical Outcomes and Efficiencies of HIFU (High-Intensity Focused Ultrasound), Da Vinci Robotic Surgery and Laparoscopic Surgery for Uterine Fibroids: A Systematic Review and Meta-Analysis." Clinical and Experimental Obstetrics and Gynecology 49(11): 248.
	Background: To compare the clinical outcomes and treatment efficiencies of advanced surgical treatments including High-Intensity Focused Ultrasound (HIFU), robotic surgery and laparoscopic surgery in the uterine fibroid patients. Method(s): A total of 512 studies from 1995 to 2021 were identified by screening from Science Direct, Cochrane library, Medscape, Willey Online Library, PubMed, and Taylor Francis. From these studies 29 articles were qualitatively included in our systematic review and 24 of them considered quantitively eligible were included in the meta-analysis. Study analyzed by pooling the weighed mean difference (WMD) with the 95% confidence interval (CI) were study provided as a mean + (SD) and pooled risk ratio (RR) was expressed for dichotomous variables. Pooled results were assessed with either a random-effect or fixed-effect model. Heterogeneity was evaluated using the I2 statistic. Result(s): Comparison of HIFU and robotic surgeries with operation times of 86.13 +/- 36.37 minutes to 120.2 +/- 63 minutes and 166 +/- 48.5 minutes to 278 +/- 67 minutes were higher significant differences (I2 = 97%, p < 0.00001), (WMD -111.88 [-189.68, -34.08]) with statistically significant (p = 0.005). Comparison of HIFU and laparoscopic surgery in operation time of 86.13 +/- 36.37 minutes to 120.2 +/- 63 minutes and 79 +/- 30 minutes to 106.4 +/- 38.5 minutes were not statistically significant (p = 0.75) with higher significant differences heterogeneity (I2 = 96%, p < 0.00001), (5.51 [-27.82, 38.83]). Comparison of between blood losses and fibroid sizes at 154 +/- 75 mL to 278 +/- 164.6 mL and 6.5 +/- 2.9 cm to 13.6 +/- 3.1 cm respectively in laparoscopic surgery was higher significant differences (I2 = 91%, p < 0.0007), (WMD 202.29 [87.77, 316.80]) with statistically significant (p = 0.0005). Between hospital stay and blood loss in laparoscopic surgery at 1.2 +/- 0.9 days to 5.4 +/- 0.2 days and 200 +/- 107 mL to 278 +/- 164.6 mL showed significant differences (I2 = 90%, p < 0.0001), (WMD -269.71 [-361.33, -178.09]) with statistically significant (p < 0.00001) while in robotic surgery was not significant. The follow up uterine fibroid symptom & health-related quality of life questionnaire (UF-QOL) at 3 months 45.3 + 26.9 to 70.6 + 26.9 in fibroids group and 61.6 + 41.4 to 79.64 + 17.91 in adenomyosis group and both shows significantly different (I2 = 83%, p = 0.02), (WMD 14.08 [4.42, 23.75]) with statistically significant (p = 0.0004) and (I2 = 97%, p < 0.00001), (WMD -15.95 [-28.06, -3.84]) with (p = 0.010). SSS follow up 3 months 27.2 + 15.7 to 36.6 + 7.9 in fibroids of HIFU, the heterogeneity test showed significant differences (I2 = 95%, p < 0.00001), (WMD 16.22 [8.33, 24.11]) with statistically significant (p < 0.0001). In terms of pregnancy outcome, delivery outcome in live birth between HIFU and laparoscopic surgery 4 (8) within 165 (219) and (7) 23 within 158 (224), the heterogeneity was not significant (I2 = 0%, p = 0.44), (RR 1.06 [0.97, 1.17]) neither with for risk of delivering was not significant (p = 0.20). Conclusion(s): HIFU treatment reveals more efficient clinical and treatment outcomes than robotic or laparoscopic surgery, including improved symptoms, absence of bleeding, shorter operative time, shorter recovery time, and good benefits in both short-term and long-term quality-of-life.Copyright: © 2022 The Author(s).

Otgontuya, A., et al. (2023). "Comparison of the treatment efficacies of HIFU, HIFU combined with GnRH-a, and HIFU combined with GnRH-a and LNG-IUS for adenomyosis: A systematic review and meta-analysis." Taiwanese Journal of Obstetrics & Gynecology 62(2): 226-238.
	To compare the treatment efficacies of high-intensity focused ultrasound (HIFU), HIFU combined with gonadotrophin-releasing hormone agonist (GnRH-a), and HIFU combined with GnRH-a and levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis. We conducted a literature search in SCIENCE DIRECT, COCHRANE LIBRARY, WILLEY ONLINE LIBRARY, PUBMED, and TAYLOR FRANCIS. A total of 471 articles identified, 12 were included in a systematic review, and 11 of them deemed quantitively eligible included in the meta-analysis. The efficacies of the three treatment regimens were assessed using the dysmenorrhea and menstrual scores at 3, 6, 12, 24 months. Of the three regimens, HIFU combined with GnRH-a and LNG-IUS provides the best outcome. On dysmenorrhea score at 6 months there was significantly different higher heterogeneity with P < 0.00001 (I 2 = 100% WMD 21.44 [6.34, 36.53]) with statistical significance P = 0.005. At 12 months there was significantly different higher heterogeneity P < 0.00001 (I 2 = 100% WMD 23.47 [6.00, 40.94]) with statistically significant P < 0.008. At 24 months there was significantly different higher heterogeneity P < 0.0005 (I 2 = 92% WMD 6.05 [4.81, 7.30]) with statistical significance P < 0.00001. HIFU combined with GnRH-a and LNG-IUS on menstrual score at 3 months was significantly different higher heterogeneity with P < 0.00001 (I 2 = 100% WMD 56.23 [16.01, 96.45]) with statistical significance P = 0.006. At 6 months there was significantly different higher heterogeneity P < 0.00001 (I 2 = 99% WMD 93.86 [64.15, 123.57]) with statistical significance P < 0.00001. At 12 months there was significantly different higher heterogeneity P < 0.00001 (I 2 = 99% WMD 97.13 [67.81, 126.46]) with statistical significance P < 0.00001 compared to treatments with only HIFU and HIFU combined with GnRH-a. HIFU combined with GnRH-a and LNG-IUS treatment is more effective than only HIFU monotherapy and HIFU combined with GnRH-a.; Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose. (Copyright © 2023. Published by Elsevier B.V.)

Otonkoski, S., et al. (2020). "Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 37(1): 1293-1300.
	Introduction: Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique.; Materials and Methods: 17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401.; Results: Oxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin ( p ≤ 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups ( p = 0.04).; Conclusion: Oxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner.

Otsuka, I. (2022). "Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy." Cancers 14(18).
	Endometrial cancer is the most common gynecological tract malignancy in developed countries, and its incidence has been increasing globally with rising obesity rates and longer life expectancy. In endometrial cancer, extrauterine disease, in particular lymph node metastasis, is an important prognostic factor. Nevertheless, pelvic lymphadenectomy is not considered to have a therapeutic benefit, as it did not improve survival in randomized studies. However, lymphadenectomy may have a therapeutic benefit if adjuvant therapy can be omitted without decreasing oncological outcomes, as the long-term quality of life is maintained by avoiding morbidities associated with adjuvant therapy. In intermediate- and high-risk endometrioid endometrial carcinomas, adjuvant therapy may be safely omitted without decreasing long-term survival by open surgery including systematic pelvic and para-aortic lymphadenectomy when patients are node-negative. Systematic lymphadenectomy may remove undetectable low-volume lymph node metastasis in both pelvic and para-aortic regions, and open surgery may reduce vaginal recurrence even without vaginal brachytherapy. However, lymphadenectomy may not improve survival in elderly patients and patients with p53-mutant tumors. In this review, I discuss the characteristics of lymph node metastasis, the methods of lymph node assessment, and the therapeutic benefits of systematic lymphadenectomy in patients with intermediate- and high-risk endometrioid endometrial carcinoma.

Otsuka, I. (2023). "Primary Retroperitoneal Carcinomas: New Insights into Pathogenesis and Clinical Management in Comparison with Ovarian Carcinomas and Carcinoma of Unknown Primary." Cancers 15(18): 4614.
	Primary retroperitoneal carcinomas are very rare tumors. Their pathogenesis remains unknown but may be associated with that of ovarian carcinomas, considering the similarity in morphology and gender preference. Although metaplasia of coelomic epithelium is the most widely accepted theory, the pathogenesis of retroperitoneal carcinomas may differ by histologic subtype, like ovarian carcinomas. Mucinous carcinoma, which develops in both women and men, may originate in both primordial germ cells and Walthard cell nests that may be derived from the fallopian tube. Serous carcinomas may be associated with endosalpingiosis, the presence of fallopian tube-like epithelium outside the fallopian tube, and a remnant Mullerian tract. Endometrioid and clear cell carcinomas appear to be associated with extraovarian endometriosis. Additionally, both carcinomas in the retroperitoneal lymph nodes may be metastatic diseases from endometrial and/or renal cell cancer that regress spontaneously (carcinoma of unknown primary). Retroperitoneal carcinomas are difficult to diagnose, as they have no characteristic symptoms and signs. Surgery is the cornerstone of treatment, but the necessity of chemotherapy may depend on histological subtype. Further studies are necessary, in particular studies on endosalpingiosis, as endosalpingiosis is a poorly understood condition, although it is associated with the development of both serous and mucinous carcinomas.Copyright © 2023 by the author.

Otsuka, I., et al. (2022). "Open Surgery including Lymphadenectomy without Adjuvant Therapy for Uterine-Confined Intermediate- and High-Risk Endometrioid Endometrial Carcinoma." Current oncology (Toronto, Ont.) 29(5): 3728-3737.
	Minimally invasive surgery may not be an appropriate surgical approach in intermediate- and high-risk endometrial carcinoma, even though adjuvant therapy is given. The objective of this study was to evaluate the results of open surgery including lymphadenectomy without adjuvant therapy in patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma. Two hundred fifty-six patients with uterine-confined endometrioid endometrial carcinoma were treated with open surgery, including pelvic with or without para-aortic lymphadenectomy. Of the 81 patients with uterine-confined intermediate- or high-risk disease, 77 were treated with systematic lymphadenectomy without adjuvant therapy. Seven patients developed recurrence, comprising 5.5% (3/55) and 18.2% (4/22) of the intermediate- and high-risk patients, respectively. The time to recurrence was 1-66 months. The sites of recurrence were the vaginal apex ( n = 2), lung ( n = 2), vaginal sidewall ( n = 1), pelvic lymph nodes ( n = 1), and para-aortic to supraclavicular nodes ( n = 1). Of these, five patients were alive without disease after salvage treatment, but two understaged high-risk patients died of disease. The five-year disease-specific survival rates of intermediate- and high-risk patients were 100% and 90%, respectively. The present study indicated that patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma had excellent survival when treated with open surgery, including lymphadenectomy alone. The safety of omitting adjuvant therapy should be evaluated in prospective randomized trials comparing open surgery with minimally invasive surgery.

Ott, J., et al. (2022). "Dydrogesterone after 60 years: a glance at the safety profile." Gynecological Endocrinology 38(4): 279-287.
	Objective: To provide an evidence-based safety and tolerability overview of dydrogesterone under various progesterone-deficient conditions as a commemoration of its role in managing women's reproductive health over the past 60 years. Method(s): To identify relevant publications, we used a semi-systematic approach, which included performing a structured search through the PubMed and Cochrane central databases as well as an unstructured search for publications published in English from 2010 onward with human clinical data. Result(s): A total of 32 relevant clinical studies were identified. Results were reported in the context of overall adverse events (AEs) and segregated according to various progesterone-deficient conditions. AEs concerning breasts (breast cancer risk), the endometrium (endometrial cancer risk), venous thromboembolism risk, and cardiovascular risk were found to be minimal when dydrogesterone was used as part of a menopausal hormone therapy regimen lasting <=260 weeks. Vagina-related AEs, such as bleeding, discharge, irritation, and difficult coitus, occurred less frequently with dydrogesterone when used as luteal phase support in the context of assisted reproductive techniques (ARTs). However, other common AEs, such as headache, dizziness, abdominal pain, flatulence, and nausea, occurred more frequently with dydrogesterone. No maternal complications or congenital anomalies could be linked to dydrogesterone usage during ARTs or during early pregnancy to prevent recurrent miscarriages. Studies on dydrogesterone in endometriosis and premenstrual syndrome remain scarce. Conclusion(s): Post-approval, dydrogesterone has displayed a favorable safety and tolerability profile during its 60-year use, which is reassuring, considering its important role in managing women's reproductive health.Copyright © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Ottaviano, M., et al. (2022). "Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas." Biomedicines 10(1).
	Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.

Otten, L. A., et al. (2021). "Pazodoble-pazopanib vs. pazopanib plus gemcitabine in relapsed or metastatic uterine leiomyosarcomas or uterine carcinosacomas." International Journal of Gynecological Cancer 31(SUPPL 1): A153‐A154.
	Introduction/Background As there are only a few therapy options for advanced or recurrent leiomyosarcoma (LMS) and Carcinosarcomas (CS), new effective drug combinations with an acceptable toxicity profile are urgently needed. Pazopanib is an orally available second‐generation multi targeted tyrosine kinase inhibitor (TKI), targeting among others VEGFR, PFGG and c‐kitand is approved in soft tissue sarcomas. A phase I study evaluated the combination of pazopanib and gemcitabine and showed an acceptable toxicity profile. We aim to test the activity of the combination therapy in patients with LMS in a randomized setting and to describe the activity in CS. Methodology The PazoDoble study is a prospective, randomized, open‐label, multicentre phase II trial. Patients with relapsed or metastatic uterine LMS or uterine CS are eligible for participation. LMS are randomised in a 1:1 fashion into two treatment arms. A: pazopanib 800 mg p.o./d plus gemcitabine 1000mg/m2 i.v. over 30 min d1 und d8 q3w or B: pazopanib 800 mg p.o./d. Uterine CS will be enrolled only in Arm A. Duration of therapy will be maximum 18 months or until progression, death or unacceptable toxicity. Primary Endpoints are the six month PFS and clinical progression; Secondary endpoints are the objective response rate, duration of response, time to progression, OS, toxicity and tolerability and quality of life. A previousatment with doxorubicin or any contraindications against doxorubicin and an ECOG of 0 or 1 are mandatory. Clinical and imaging follow‐up are scheduled every three month until disease progression or death. Enrolment was started in October 2019 at nine sites. Until now, 12 Patients are enrolled (5 CS and 7 LMS). We aim to include 87 patients with LMS and 20 with CS. The primary endpoint will be analysed as the ratio of the number of patients showing no progress after 6 month divided by the number of evaluable patients. A drop‐out rate of 5% was assumed. Result(s) Conclusion In the clinical setting of advanced and recurrent LMS and CS there are no well‐evaluated therapies available. This trial is clinically highly relevant and offers opportunity for patients to receive promising therapy.

Ou, H., et al. (2022). "Ovarian Response, Pregnancy Outcomes, and Complications Between Salpingectomy and Proximal Tubal Occlusion in Hydrosalpinx Patients Before in vitro Fertilization: A Meta-Analysis." Frontiers in surgery 9: 830612.
	Objectives: Contradictory findings exist in studies comparing salpingectomy and proximal tubal occlusion (PTO) in treating hydrosalpinx patients before in vitro fertilization (IVF). Therefore, this meta-analysis aimed to comprehensively compare ovarian response, pregnancy outcomes, and complications between salpingectomy and PTO in treating these patients.; Methods: Embase, PubMed, and Web of Science were searched to identify relevant articles published from 1980 to August 31, 2020. Eight studies that involve 716 hydrosalpinx patients before IVF were included, among whom 408 patients received salpingectomy and 308 patients received PTO. The data were pooled; the standardized mean difference (SMD) or odds ratio (OR) was calculated.; Results: Proximal tubal occlusion-treated patients had higher fertilization rate (SMD = 0.35, 95% CI: 0.11-0.59), while similar days of controlled ovarian hyperstimulation (COH) (SMD: 0.15, 95% CI: -0.36-0.67) and number of retrieved oocytes (SMD = -0.22, 95% CI: -0.54-0.10) compared with salpingectomy-treated patients. Furthermore, no difference of implantation rate (OR = 1.17, 95% CI: 0.62-2.20), clinical pregnancy rate (OR = 0.82, 95% CI: 0.59-1.15), ongoing pregnancy rate (OR = 0.64, 95% CI: 0.36-1.13), or live birth rate (OR = 0.67, 95% CI: 0.16-2.72) was shown between salpingectomy-treated patients and PTO-treated patients. Additionally, ectopic pregnancy rate (OR = 1.13, 95% CI: 0.21-5.92) and miscarriage rate (OR = 0.88, 95% CI: 0.31-2.48) were similar between salpingectomy-treated patients and PTO-treated patients.; Conclusion: Proximal tubal occlusion exhibits a higher fertilization rate but no obvious benefits on days of COH, number of retrieved oocytes, pregnancy outcomes, and complications over salpingectomy in hydrosalpinx patients before IVF.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Ou, Sun, Lin and Ma.)

Ou, Y., et al. (2023). "Effects of an "Internet +" Multidisciplinary Management Model Oriented by Nurse Specialists on Obesity Combined with Polycystic Ovary Syndrome." Clinical and Experimental Obstetrics and Gynecology 50(6): 125.
	Background: Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disease in women of reproductive age, and its treatment mainly relies on adjusting lifestyle and oral drug therapy. With the development of the Internet and shared economy, the "Internet + nursing services" model has become increasingly popular, is presently an essential component of the Health Wellness project and has a promising future. Method(s): This study involved 100 gynecological outpatients with PCOS from the Foshan Maternal and Child Health Hospital. They were divided into a control (routine nursing) and an experimental ("Internet +" multidisciplinary management oriented by nurse specialists) group according to a predefined nursing scheme. Several indicators, such as rates of ovulation and pregnancy, body mass index (BMI), waistline, serum hormone levels, metabolic indicators and psychological status of patients, were compared between the two groups before and half a year after the nursing intervention. Result(s): Six months after the intervention, the experimental group had significantly higher ovulation and pregnancy rates than the control group (88.00% vs. 68.00%, 48.00% vs. 22.00%, p < 0.05). Additionally, the experimental group showed a significant decrease in BMI, waistline, serum hormone levels (i.e., testosterone and luteinizing hormone [LH]) and homeostasis model assessment of insulin resistance (HOMA-IR) compared to the control group (p < 0.05). However, no obvious differences were observed in follicle-stimulating hormone (FSH) and fasting blood glucose (FBG) (p > 0.05) compared with the control group. Further, patients in the experimental group also displayed better psychological status, with a significant decrease in self-rating anxiety scale (SAS) scores and self-rating depression scale (SDS) half a year after intervention (p < 0.05). Conclusion(s): Interventions using the "Internet +" multidisciplinary management model oriented by nurse specialists not only effectively increased the rates of ovulation and pregnancy of PCOS patients but also significantly improved patients' indicators such as BMI, waistline, serum hormone levels, metabolic indicators, and psychological status.Copyright: © 2023 The Author(s).

Ou, Y. Y., et al. (2021). "Effects of whole-course standardized nursing and humanistic care on the sleep condition and quality of life of elderly patients undergoing hysterectomy for cervical cancer." European Journal of Gynaecological Oncology 42(1): 154‐160.
	Objective: To explore the effects of whole‐course standardized nursing and humanistic care on the sleep condition, psychological status and quality of life of elderly patients undergoing total hysterectomy for cervical cancer. Methods: 104 elderly patients admitted to our hospital from September 2017 to September 2019 were evenly divided into observation and control groups according to the random number table method. The observation group was given standardized whole‐course nursing and humanistic care, while the control group was given routine nursing care. The sleep quality, negative emotions, quality of life, incidence of complications and nursing satisfaction of the two groups were observed. Results: After intervention, the time used to fall asleep in the observation group was shorter than that in the control group (P < 0.05), while the duration of continuous sleep and total sleep were both longer in the observation group (P < 0.05). The results for the scores of the scales for evaluating the sleep quality, negative emotions, quality of life, and level of hope also showed that, in the perioperative period, the nursing effect of the whole‐course standardized nursing and humanistic care was significantly improved. Conclusion: The patients' sleep condition, negative emotions, quality of life and level of hope were significantly improved. In addition, the incidence of postoperative complications was low, and the nursing satisfaction of the patients was high, so this nursing strategy is worthy of clinical application.

Ou, Z., et al. (2023). "Effects of reduced follicle-stimulating hormone dosage before human chorionic gonadotropin trigger on in vitro fertilization outcomes." BMC Pregnancy and Childbirth 23(1): 612.
	Objective: To determine whether a reduced dose of follicle-stimulating hormone (FSH) before human chorionic gonadotropin (hCG) trigger during ovarian stimulation can affect in vitro fertilization (IVF) outcomes.; Methods: This study included 347 patients with a normal ovarian response who received a reduced dose of FSH before hCG trigger for 2-3 days (Group A) and 671 patients who did not receive a reduced dose (Group B) from a university-affiliated IVF center between January 2021 and December 2022. The primary endpoint was estrogen (E2) and progesterone (P) levels on the day of hCG trigger, fresh embryo transfer cycles, laboratory outcomes, and clinical outcomes between the two groups.; Results: On the day of hCG trigger, Group A had significantly lower E2 and P levels than those in Group B (3454.95 ± 1708.14 pg/mL versus 3798.70 ± 1774.26 pg/mL, p = 0.003; and 1.23 ± 0.53 ng/mL versus 1.37 ± 0.59 ng/mL, p < 0.001, respectively). The proportion of patients with P levels ≥ 1.5 ng/mL was 22.48% in Group A compared to 34.58% in Group B (p < 0.001), while the proportion of patients with E2 ≥ 5000 pg/mL was 15.27% in Group A compared to 25.93% in Group B (p < 0.001). The fresh embryo-transfer cycle rate in Group A was higher than that in group B (54.47% and 32.64%, respectively; p < 0.001). Despite the reduction in FSH dosage, there were no significant differences between groups regarding the number of oocytes retrieved, total number of mature oocytes, normal fertilization rate, cleavage rate, Day 3 top-quality rate, implantation rate, pregnancy rate per cycle, and early pregnancy loss rate.; Conclusion: While a reduced dose of FSH prior to hCG trigger during ovarian stimulation did not significantly affect IVF outcomes, it was associated with lower E2 and P levels, resulting in fewer cycles with E2 ≥ 5000 pg/mL and P ≥ 1.5 ng/mL on the day of the hCG trigger. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ouasti, S., et al. (2022). "Prospective study of fertility-sparing treatment with chlormadinone acetate for endometrial carcinoma and atypical hyperplasia in young women." International Journal of Gynecology and Obstetrics 157(2): 452-457.
	Objective: To confirm that the efficiency of the use of chlormadinone acetate for 6 months to obtain remission of atypical hyperplasia or endometrial carcinoma is comparable to that of the use of other fertility-sparing treatments. Method(s): The present study is based on the PREFERE prospective registry. All the patients received 3 or 6 months of chlormadinone acetate and were evaluated by hysteroscopic resection and pipelle sampling every 3 months. Result(s): Ninety-four patients were included. Seventy-nine patients achieved complete remission at 6 months (84%). No patients stopped treatment because of a lack of tolerance. Twenty-four per cent of the patients achieved a live birth. Conclusion(s): Chlormadinone acetate is an effective and well-tolerated fertility-sparing treatment. Its benefits over other progestins are its tolerability, and its absence of contraindications, which make it a good choice for patients with thromboembolism and high vascular risk.Copyright © 2021 International Federation of Gynecology and Obstetrics.

Ouasti, S., et al. (2023). "Adherence to ESGO guidelines and impact on survival in obese patients with endometrial cancer: a multicentric retrospective study." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(12): 1950-1956.
	Objectives: Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m 2 ). The secondary objectives were the impact on overall survival and recurrence-free survival.; Methods: All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m 2 ), obese (BMI 30-40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies.; Results: In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04).; Conclusion: Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Ouchi, N., et al. (2022). "Effects of Thrombophilia and Antithrombotic Therapy on Embryonic Chromosomal Aberration Rates in Patients with Recurrent Pregnancy Loss." Journal of Nippon Medical School = Nippon Ika Daigaku zasshi 89(1): 40-46.
	Background: Miscarriage occurs in 10-15% of pregnancies and recurrent pregnancy loss (RPL) occurs in 1% of couples hoping for a child. Various risk factors, such as thrombophilia, uterine malformation, and embryonic chromosomal aberration cause RPL. We hypothesized that antithrombotic therapy for RPL patients with thrombophilia would reduce miscarriage due to thrombophilia, which would reduce the total miscarriages and result in a relative increase in miscarriage due to embryonic chromosomal aberrations. In this study, we investigated the incidence of chromosomal aberrations in products of conception in RPL patients with and without antithrombotic therapy.; Methods: We performed a single-center, retrospective review of cases diagnosed as miscarriage with embryo chromosome analysis between July 1, 2000, and May 31, 2019. Rates of chromosomal aberration were compared between RPL patients with and without thrombophilia or antithrombotic therapy.; Results: One hundred and-ninety RPL cases were analyzed. The average age was 37.4 ± 4.3 years, and the average number of previous pregnancy losses was 2.2 ± 1.1. The overall chromosomal aberration rate was 67.4% (128/190). There was no difference in the chromosomal aberration rate between the factors for RPL, with or without thrombophilia, and antithrombotic therapy. Only advancing maternal age had significant correlation to increased embryo chromosomal aberration rates.; Conclusions: With or without antithrombotic therapy, miscarriage was caused by embryonic chromosome abnormalities at a certain rate. Antithrombotic therapy in RPL patients with thrombophilia may reduce abortions due to thrombophilia, which may also normalize the rate of embryonic chromosome aberrations in the subsequent miscarriages.

Ouh, Y. T., et al. (2022). "Prevalence and Treatment of Vulvar Cancer From 2014-2018: A Nationwide Population-Based Study in Korea." Journal of Korean medical science 37(4): e25.
	BACKGROUND: Vulvar cancer is one of the rare gynecologic malignancies. Despite the recent increasing trend of vulvar cancer in western countries due to the increased infection of human papillomavirus, there has been no study for population-based incidence of vulvar cancer in Korea. We aimed to investigate the prevalence and treatment of vulvar cancer in South Korea between 2014 and 2018. METHOD(S): Data from patients diagnosed and treated with vulvar cancer between 2014 and 2018 were obtained from the Health Insurance Review and Assessment Service/National Inpatient Sample (National In-Patient Sample) in South Korea. RESULT(S): A total of 4,636,542 women were identified through the HIRA-NIS database from 2014 to 2018, of which 259 patients were diagnosed and treated for vulvar cancer. The mean age diagnosed with vulvar cancer was 62.82 (+/- 14.30) years in 2014, 64.19 (+/- 16.79) years in 2015, and 67.40 (+/- 14.41) years in 2016. In terms of treatment modalities, the most frequent treatment was surgery only without chemotherapy or radiation therapy. In the age-specific prevalence analysis, vulvar cancer was the most prevalent among those over 70 years old. According to multiple regression analysis, patients' age was significantly associated with the prevalence of vulvar cancer. Vulvar cancer was more prevalent in women with low socioeconomic status (SES) compared to those with high SES in 2018 (OR, 4.242; P < 0.001). CONCLUSION(S): Considering the high prevalence of vulvar cancer in the elderly, it is necessary to establish a new strategy for early screening and treatment.Copyright © 2022 The Korean Academy of Medical Sciences.

Oulu University, o. (2022). Robotic Versus Laparoscopic Surgery for Deep Endometriosis.
	No Results Available Procedure: Minimally invasive surgery NRS (Numeric rating scale) Score for pain|Intraoperative measures|Factors concerning ERAS (Enhanced recovery after surgery)|Cost|Complications|Endometriosis-related quality-of-life|General 15 dimensional health-related quality-of-life questionnaire|Sexual quality-of-life questionnaire Female Not Applicable 70 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ROBtrial1 December 31, 2026

Ouyang, Y., et al. (2023). "Septum Resection Prior to In Vitro Fertilization-Embryo Transfer: A Retrospective Controlled Study." Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 42(5): 1129-1137.
	Objectives: To investigate the effectiveness of surgery for septate uterus in infertile patients before in vitro fertilization-embryo transfer (IVF-ET).; Methods: The data of 937 infertile patients with septate uterus and achieved singleton pregnancy after IVF-ET from January 2014 to December 2015 were retrospectively analyzed. Thousand five hundred seventy-eight infertile patients with a normal uterus who achieved singleton pregnancy during the same period were selected as the control group. Patients with septate uterus were divided into two groups according to whether the septum was resected. The pregnancy and perinatal outcomes of the surgical group and the nonsurgical group were compared with the control group. The secondary infertility patients who were surgically corrected septa were also chosen as self-controls and an analysis was performed on their fertility outcomes pre- and post-surgery.; Results: Compared with the control group, the surgical group had increased rates of early miscarriage, preterm delivery, and low birthweight and a significantly reduced live birth rate (P < .05). The outcomes of the nonsurgical and control groups were similar. Using secondary infertility patients who were surgically corrected septa as self-controls, after surgery, the rates of miscarriage and ectopic pregnancy were significantly lower and the live birth rate was significantly higher (P ≤ .001); however, perinatal mortality was not significantly different before and after surgery.; Conclusions: Patients with a septum depth greater than 10 mm or 5-10 mm associated with a history of unexplained recurrent miscarriage, IVF failure, or infertility might benefit from resection of the uterine septum with hysteroscopic metroplasty. (© 2022 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

OuYang, Z., et al. (2020). "Single-dose versus multidose metronidazole for the treatment of vaginal trichomoniasis: A meta-analysis." European Journal of Obstetrics and Gynecology and Reproductive Biology 255: 56-62.
	Objective: The purpose of this meta-analysis is to further explore the effectiveness of multidose metronidazole (MTZ) and single-dose MTZ in the treatment of trichomoniasis. Study design: Search all the literature on MTZ for trichomoniasis in the Pubmed, Ovid Embase, Ovid MEDLIN and Cochrane Library databases. The search period is from the establishment of the database to September 10, 2020. Two authors independently screened the literatures based on inclusion and exclusion criteria, and independent extraction and integration of literature data. The main observation indicators were treatment failure rate and side-effects. Data analysis was performed using RevMan5.2 software. The risk ratio (RR) and 95 % confidence interval (CI) were used as the effect scale indicators of the counting data. P < 0.05 was considered to be statistically significant. Result(s): A total of 2114 articles were retrieved. After screening, a total of 7 articles were included, including 5 randomized controlled trial (RCT) studies and 2 case-control studies. 745 cases were treated with single-dose MTZ, and 732 cases were treated with multidose MTZ. The single-dose MTZ had a higher failure rate for trichomoniasis than the multidose MTZ, and the difference was statistically significant (RR = 1.07, 95 %CI, 1.03-1.11, P = 0.0003). When a HIV-positive study was excluded, the failure rate of the single-dose MTZ was still significantly higher than that of the multidose MTZ (RR = 1.62, 95 %CI, 1.19-2.22, P = 0.002). The side-effects of the single-dose MTZ were higher than those of the multidose MTZ, but the difference was not statistically significant (RR = 1.06, 95 %CI, 0.88-1.27, P = 0.53). Conclusion(s): Although based on available data, multidose MTZ is more effective than single-dose MTZ for trichomoniasis, this advantage is not as obvious as previously proven. This small advantage may be lower if considering the compliance of multidose MTZ in the real world. Therefore, more high-quality studies are needed to confirm this before suggesting a multidose MTZ as the first line treatment for HIV-negative trichomoniasis.Copyright © 2020 Elsevier B.V.

Overholt, T., et al. (2022). "Sacrospinous Hysteropexy: Native Tissue Compared to Mesh Augmented Repair for the Surgical Management of Uterovaginal Prolapse." International Urogynecology Journal 33(Supplement 2): S469.
	Introduction: The anterior approach to sacrospinous hysteropexy was popularized by transvaginal mesh kits such as the Uphold Lite Vaginal Support SystemTM. Following withdrawal of these kits from the United States market, we hypothesized that similar efficacy could be achieved with native tissue anterior repair, reattachment of the pubocervical fascia to the cervix, and then fixation of the anterior cervix to the right sacrospinous ligament using 1 permanent and 1 delayed absorbable suture. Few comparative studies of the safety and efficacy profiles of an anterior approach to sacrospinous hysteropexy using native tissue versus a mesh-augmented repair with Uphold Lite exist. Objective(s): The primary aim was to compare success rates of an anterior approach to sacrospinous hysteropexy using native tissue compared to transvaginal mesh. The secondary aim was to assess intra- and postoperative complications. Method(s): A retrospective cohort analysis of women with uterine prolapse who underwent transvaginal sacrospinous hysteropexy between 01/01/2016-12/31/2020 at a tertiary care referral center was performed. Women were analyzed in two groups: Uphold and native tissue hysteropexy (SSLF). Demographic, past medical/surgical history, associated urogynecological symptoms, and intra- and post-operative data were reviewed. Success and complication data were compared through all available follow up data. Composite success was defined as the following: 1) No subjective vaginal bulge symptoms, 2) No retreatment for prolapse, and 3) No recurrent prolapse beyond the hymen and the apex not descended > 1/3 of the total vaginal length. Descriptive and bivariate statistics were performed as indicated. Result(s): A total of 97 women, 40 Uphold and 57 SSLF patients, met inclusion criteria and were compared. All demographic and past medical/ surgical history data are included in Table 1. Women in the Uphold group were more likely to have undergone a prior pelvic organ prolapse surgery (p=0.003) and have a history of prior intra-abdominal surgery (p=0.015). Median pre-operative POP-Q was Stage III in each group. There were no differences in surgical time (102.4-31.4 vs 109.8-19.6 minutes, p=0.211) or ASA classification (p=0.211) between groups. Post-procedure, the median follow-up time was 8.2 months. The overall composite success rate was 95% in each group: Anatomic success was demonstrated in 100% of patients; vaginal bulge symptoms were reported by 2 women in the Uphold group compared to 3 in the SSLF group (p=0.999); and one woman in the Uphold group underwent retreatment with a pessary compared to 3 women in the SSLF group who underwent re-treatment (2 pessary, 1 repeat surgery; p=0.639). Three intra-operative complications were reported in the SSLF group: 1 ureteral injury, 1 urethral injury, and 1 blood transfusion. There were no reported intra-operative complications in the Uphold group. There was no difference in 30-day complication rates between groups (p=0.775; Table 2). No mesh related complications in the Uphold group were reported. Conclusion(s): For women undergoing sacrospinous hysteropexy through an anterior approach, 95% achieved surgical success and the use of a mesh-augmented repair did not confer any benefit in terms of efficacy or complications when compared to native tissue repair only. Further long-term data is needed to continue assessment of native tissue sacrospinous hysteropexy.

Overholt, T., et al. (2023). "NATIVE TISSUE ANTERIOR SACROSPINOUS HYSTEROPEXY IS AN EFFECTIVE AND SAFE APPROACH FOR PRIMARY UTEROVAGINAL PROLAPSE COMPARED TO MESH AUGMENTED REPAIR." Journal of urology 209(Supplement 4): e91-e92.
	INTRODUCTION AND OBJECTIVE: Anterior sacrospinous hysteropexy (SSH) was popularized by transvaginal mesh kits. Following market withdrawal, we hypothesized similar efficacy could be achieved through native tissue reattachment of the pubocervical fascia to the cervix with fixation of the anterior cervix to the sacrospinous ligament. Few analyses exist for the efficacy of anterior SSH using native tissue versus mesh augmented repair. METHOD(S): A retrospective analysis of women who underwent transvaginal SSH at a tertiary center between 01/16-12/21 was performed. Women underwent mesh augmented repair using the Uphold Lite Vaginal Support System or a native tissue anterior SSH. Demographic, clinical, and operative data were reviewed. Composite success was defined as no bulge symptoms, no prolapse retreatment, and no recurrent prolapse beyond the hymen with apex non descended > 1/3 the total vaginal length. Descriptive and bivariate statistics were performed as indicated. RESULT(S): We compared the data for 97 women (40 mesh augmented; 57 native tissue). There was no difference in age, BMI, or vaginal delivery history between groups (p > 0.05). Median pre operative POP Q was stage III. Those in the mesh augmented group were more likely to have undergone a prior prolapse (p=0.003) or intra abdominal (p=0.015) surgery. There was no difference in surgical time (p=0.211) between groups (Table 1). The median post procedure follow up time was 8.2 months. The composite success rate was 95% for all women (Table 1). Anatomic success was demonstrated in 100% of patients. Vaginal bulge symptoms were reported by 2 women in the mesh augmented group compared to 3 in the native tissue group (p=0.999). One woman in the mesh augmented group underwent retreatment (pessary) compared to 3 in the native tissue group (2 pessary, 1 surgery; p=0.639). There was no difference in intra operative (p=0.999) or 30 day post operative (p=0.775) complication rate between groups (Table 1). CONCLUSION(S): Ninety five percent of women who underwent an anterior SSH achieved surgical success. The use of mesh augmentation did not confer any added benefit in terms of efficacy or complications when compared to native tissue. Further long term data is needed to continue our assessment of native tissue anterior SSH. (Figure Presented).

Overholt Tyler, L., et al. (2023). "Anterior approach sacrospinous hysteropexy: native tissue compared with mesh-augmented repair for primary uterovaginal prolapse management." International Urogynecology Journal 34(10): 2603-2609.
	Introduction and Hypothesis: Anterior sacrospinous hysteropexy (SSH) was popularized by transvaginal mesh kits. Following mesh-kit market withdrawal, we hypothesized similar efficacy through native-tissue reattachment of the pubocervical fascia with fixation of the anterior cervix to the sacrospinous ligament. Few analyses for anterior native-tissue versus mesh-augmented SSH exist.; Methods: A retrospective analysis of women who underwent transvaginal anterior SSH between 01 January 2016 and 31 December 2022 was performed. Women who underwent a mesh-augmented (Uphold Lite Vaginal Support System™) versus native-tissue repair were compared. Composite success was defined as no bulge symptoms, no retreatment, and no recurrence beyond the hymen with apex nondescended > one third of the total vaginal length. Descriptive and bivariate statistics were obtained as indicated.; Results: Of 223 women screened, inclusion criteria were met by 124 (40 mesh-augmented; 84 native-tissue). There was no difference in pre-operative characteristics between groups. Composite success was demonstrated in 95.2% of women with a median follow-up of 224 days (range: 30-988). Two women in the mesh-augmented group reported bulge symptoms and underwent re-treatment with a pessary. Four women in the native-tissue group reported bulge symptoms; 3 underwent re-treatment (2 pessary, 1 surgery). There were no differences in composite success rates between groups (p=0.954). There were additionally no differences in intra-operative (p=0.752) or post-operative (p=0.292) complication rates between the groups. There were no mesh-related complications, including exposure or chronic pelvic pain.; Conclusions: Ninety-five percent of women achieved surgical success and the use of mesh augmentation did not confer added benefit in terms of efficacy or complications when compared with native tissue. Further long-term data are needed to continue our assessment of native-tissue anterior SSH. (© 2023. The International Urogynecological Association.)

Ovidiu-Dumitru, I., et al. (2024). "The Pregnancy Outcomes Among Women Receiving Individualized Algorithm Dosing with Follitropin Delta: ASystematic Review of Randomized Controlled Trials."
	
Oviedo, J. D., et al. (2021). "Auricular acupressure and auricular acupuncture as an adjunct for pain management during first trimester aspiration abortion: a randomized, double-blinded, three-arm trial." Contraception 103(5): 342‐347.
	OBJECTIVES: To measure pain and anxiety during first trimester uterine aspiration when using auricular acupressure or acupuncture as an adjunct to usual care. METHODS: This randomized, double‐blinded, three‐arm trial enrolled patients undergoing an aspiration procedure for an induced abortion, a miscarriage, or other abnormal intrauterine pregnancy. Trial participants received auricular acupressure, auricular acupuncture, or placebo immediately prior to their procedures. The study began with 1:1:1 randomization, but later overenrolled into the acupressure group after providing retraining for greater fidelity to that intervention. All participants received ibuprofen and a paracervical block. Participants reported pain and anxiety levels via visual analog scores (0‐100). Our analysis compared pain scores of those receiving acupressure versus placebo, and those receiving acupuncture versus placebo. RESULTS: We randomized 177 participants over nine months and excluded data from four participants. We analyzed data from 70 participants who received acupressure, 51 who received acupuncture, and 52 who received placebo. The groups had similar baseline characteristics, including baseline pain and anxiety scores. For acupressure, acupuncture, and placebo groups, respectively, immediate post‐procedure median pain scores were 50, 55, 47.5 (p=0.88); maximum pain scores during the procedure were 77, 79, 79.5 (p=0.96); post‐procedure anxiety scores were 26, 28, and 21 (p=0.47). The acupressure group results were similar before and after retraining. CONCLUSIONS: Receiving auricular acupressure or acupuncture did not result in lower pain or anxiety scores among women undergoing vacuum aspiration compared to a placebo group. IMPLICATIONS: The results of this trial were null, thus differing from our previous study that had shown a benefit from auricular acupuncture. Given the conflicting results, incorporating these acupuncture techniques into abortion practice would be premature.

Owens, S. M., et al. (2023). "Perioperative Education and Postoperative Discharge Medications in Gynecologic Oncology Patients: Prescribing Practices, Clinical Encounters, and Patient Satisfaction." Journal of Gynecologic Surgery 39(2): 92-98.
	Objectives: The effects of an algorithm for postoperative prescriptions on opioid-prescribing practices, pain-related postdischarge clinical encounters, and patient satisfaction were studied. Material(s) and Method(s): A quality-improvement initiative was implemented at a single, tertiary-care, comprehensive cancer center. Perioperative patient education was restructured with detailed verbal and written components. An algorithm for postoperative discharge medications included prescribing nonopioid analgesics to all patients without contraindications. Opioid prescriptions were based on patients' length of stay and inpatient opioids' use. Data on opioids prescribed and postoperative encounters for pain were collected, and surveys at a postoperative visit were taken on patient satisfaction pre- and postintervention. Groups' results were compared. Result(s): The patients (107 preintervention and 90 postintervention) had similar demographics. The postintervention group had a 25% reduction in median number of opioids prescribed at discharge (p = 0.16), with similar patterns of postoperative encounters for pain and frequency of opioid refills. Patient satisfaction, assessed in 29 preintervention and 40 postintervention participants, had significant improvement; 95% postintervention participants answered that they were satisfied with their pain control, compared with 75% preintervention participants (p = 0.03). Conclusion(s): Perioperative education plus an algorithm for postoperative discharge medications in gynecologic oncology patients results in improved patient satisfaction, a trend toward fewer opioid prescriptions, and a similar pattern of postoperative pain encounters. Comprehensive perioperative education is effective for improving patient satisfaction and pairs well with an algorithmic approach to decreasing opioid prescriptions. (J GYNECOL SURG 20XX:000)© Copyright 2023, Mary Ann Liebert, Inc., publishers 2023.

Oxley, S., et al. (2022). "Quality of Life after Risk-Reducing Hysterectomy for Endometrial Cancer Prevention: A Systematic Review." Cancers 14(23).
	Background: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence.; Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes.; Results: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening.; Conclusions: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk.

Oyarzabal, E. A., et al. (2021). "Mind-Body Techniques in Pregnancy and Postpartum." Clinical Obstetrics and Gynecology 64(3): 683‐703.
	Maternal stress can perturb physiology and psychiatric health leading to adverse outcomes. This review investigates the effectiveness of several mind‐body therapies ‐ namely biofeedback, progressive muscle relaxation, guided imagery, tai chi, and yoga ‐ as interventions in reducing maternal stress and other pregnancy‐related conditions. Through randomized trials, these techniques have shown promising benefits for reducing pain, high blood pressure, stress, anxiety, depressive symptoms, labor pain and outcomes, and postpartum mood disturbances. As these interventions are easy to implement, low cost, and safe to perform in pregnancy, they should be considered as alternative, nonpharmaceutical interventions to use during pregnancy and postpartum care.

Oz, M., et al. (2022). "The safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era: a multicentre, retrospective, case-control study." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(5): 1286-1292.
	Our goal was to address the safety of major gynaecologic cancer surgery without routine preoperative COVID-19 testing in the COVID-19 era. The databases of seven gynaecologic cancer centres were searched in order to identify all consecutive gynaecologic cancer patients undergoing major surgery between March 11, 2020 and May 15, 2020 for this retrospective, case-control study. The case group consisted of patients with histopathologically confirmed gynaecologic cancers, and each case was matched with two counterparts who had undergone primary surgery before the COVID-19 pandemic. The case and the control groups were compared in terms of length of hospital stay, admission to the intensive care unit (ICU), intraoperative and postoperative complications.During the study period, 154 women with gynaecologic cancer undergoing major surgery were identified. Although the case group had more co-morbidities compared to the control group (103/154 vs. 178/308, respectively; p = .04), the median length of hospital stays, the rate of ICU admission, intraoperative complication rates and postoperative complication rates were similar in the two groups. Gynaecologic cancer surgery may be performed safely in the COVID-19 era with similar rates of ICU admission, intraoperative and postoperative complications compared to the patients operated before the COVID-19 pandemic.IMPACT STATEMENT What is already known on this subject? Many societies have announced their guidelines about the surgical management of gynaecologic cancer patients during the COVID-19 pandemic. However, most of them are not evidence-based and mostly on expert opinions. What do the results of this study add? The main findings of this retrospective, case-control study indicate that the short-term (30 day) outcomes of gynaecologic cancer patients undergoing major surgery in the COVID-19 era are similar to those who had been operated before the COVID-19 pandemic. The length of hospital stays, the rates of admission to the ICU, intraoperative and postoperative complications were comparable between women undergoing major gynaecologic cancer surgery in the COVID-19 era and the women who had been operated before the pandemic. What are the implications of these findings for clinical practice and/or further research? We can suggest that definitive surgery may be performed for gynaecologic cancer patients in the COVID-19 era if the resources permit and appropriate precautions such as social distancing, isolation and the use of personal protective equipment are taken.

Oz, Y., et al. (2023). "The effect of the Incontinence Health Belief Development Program on women's urinary incontinence awareness and health beliefs: a randomized controlled trial." International Urogynecology Journal 34(7): 1385-1393.
	Introduction and hypothesis: This study is aimed at determining the effects of the Incontinence Health Belief Development Program (IHBDP) on the urinary incontinence awareness and health beliefs of women in the pre-menopausal period. Method(s): This randomized controlled study was conducted in 160 eligible women. The pre-test and post-test data of the study were collected from experimental and control groups using the Socio-Demographic Characteristics Information Form, the Incontinence Awareness Scale, the Health Belief Scale on Urinary Incontinence and Kegel Exercise, and the Broome Pelvic Muscle Self-Efficacy Scale. The IHBDP was implemented with members of the experimental group for 5 weeks. Result(s): The women in the experimental group showed a significant difference in mean scores at the end of the program on the UI Awareness Scales, the Health Belief Scale on UI, and the Kegel Exercise compared with pre-training scores (p<0.05). In the experimental group, the factor scores and the total score of the Broome Pelvic Muscle Self-Efficacy Scale also increased. Furthermore, a statistically significant total score increase (p<0.05) was observed at the end of the program (79.8+/-8.8) compared with before the program (35.2+/-19.6). Conclusion(s): The training given to the women in the pre-menopausal period based on the Health Belief Model appears highly effective in raising awareness about UI, fostering beliefs about Kegel exercises and increasing pelvic floor muscle self-efficacy.Copyright © 2022, The International Urogynecological Association.

Oza, A. M., et al. (2022). "Overall survival results from ARIEL4: a phase III study assessing rucaparib vs chemotherapy in patients with advanced, relapsed ovarian carcinoma and a deleterious BRCA1/2 mutation."  33: S780‐.
	Background: In the primary analysis of ARIEL4 (NCT02855944), rucaparib significantly improved progression‐free survival (PFS) vs standard‐of‐care chemotherapy (CT) in patients (pts) with relapsed, heavily pretreated, BRCA1/2‐mutated ovarian carcinoma (Kristeleit et al. Lancet Oncol. 2022;23:465‐78). Here, we present final overall survival (OS) and PFS on the subsequent line of therapy (PFS2) results from the intent‐to‐treat (ITT) population. Methods: Pts were randomised 2:1 to oral rucaparib 600 mg BID or CT. In the CT group, pts with progression‐free interval (PFI) ≥1 to <6 months (platinum resistant) or ≥6 to <12 months (partially platinum sensitive) received weekly paclitaxel; pts with PFI ≥12 months (fully platinum sensitive) received investigator’s choice of platinum‐based CT (single‐agent platinum or platinum doublet). Pts in the CT group could cross over to receive rucaparib upon confirmed radiographic progression per RECIST. OS was a standalone secondary endpoint; PFS2 was an exploratory endpoint. Results: At data cutoff, 14/233 (6%) pts in the rucaparib group and 0/116 in the CT group were ongoing on assigned study treatment. Following progression on CT, 80 (69%) pts crossed over to receive rucaparib; overall, 313/349 (90%) pts received rucaparib from randomisation or after crossover. Death events have occurred in 244 (70%) pts. Efficacy endpoints are presented in the Table. Rucaparib safety was consistent with previous reports. [Formula presented] Conclusions: PFS2 was not significantly different for pts in the rucaparib or CT groups. In the ITT population, the secondary endpoint of OS favoured CT. Amongst patients with platinum‐sensitive disease, OS was similar between the treatment groups; the difference in the ITT population was driven by the platinum‐resistant subgroup. OS was confounded by the high rate of crossover, raising important questions about the optimal sequencing of PARP inhibitors in advanced disease. Clinical trial identification: NCT02855944 August 4, 2016. Editorial acknowledgement: Medical writing and editorial support were funded by Clovis Oncology, Inc. and provided by Shelly Lim and Kathleen Blake of Ashfield MedComms, an Ashfield Health company. Legal entity responsible for the study: Clovis Oncology, Inc. Funding: Clovis Oncology, Inc. Disclosure: A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline. A.A. Fedenko: Financial Interests, Personal, Invited Speaker: MSD, Amgen; Financial Interests, Personal, Advisory Board: Novartis. A.C. de Melo: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol‐Myers Squibb, F. Hoffmann‐La Roche, GlaxoSmithKline, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol‐Myers Squibb, F. Hoffmann‐La Roche, GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Sanofi; Financial Interests, Institutional, Invited Speaker: Regeneron Pharmaceuticals, Novartis, Merck Sharp and Dohme, GlaxoSmithKline, F. Hoffmann‐La Roche, Clovis Oncology, Inc., Bristol‐Myers Squibb, AstraZeneca, Amgen. Y. Shparik: Financial Interests, Personal, Other, honoraria: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Other, honoraria: Roche. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Resear h Grant: AstraZeneca, PharmaMar, Roche; Non‐Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non‐Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, ImmunoGen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non‐Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non‐Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non‐Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non‐Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non‐Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non‐Financial Interests, Member, Board of Directors: GCIG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann‐La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non‐Financial Interests, Leadership Role, Executive Board member as a Co‐Chair: GEICO; Non‐Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non‐Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non‐Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. B. Maćkowiak‐Matejczyk: Financial Interests, Personal, Invited Speaker, honoraria: AstraZeneca, GlaxoSmithKline, Roche; Financial Interests, Personal, Advisory Board: Seagen, GlaxoSmithKline; Financial Interests, Personal and Institutional, Funding: Clovis Oncology, Inc., AstraZeneca AB, AstraZeneca Pharma Poland sp zoo, MERSANA Therapeutics, MSD Polska Sp zoo, Parexel International Limited, Quiniles Eastern Holdings, Regeneron Pharmaceuticals, Roche Polska sp zoo, Seagen, Tesaro, Tesaro Bio Netherlands BV. D. Thomas: Financial Interests, Personal, Full or part‐time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K.K. LIN: Financial Interests, Personal, Full or part‐time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K. McLachlan: Financial Interests, Personal, Full or part‐time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. S. Goble: Financial Interests, Personal, Full or part‐time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. R. Kristeleit: Financial Interests, Personal, Advisory Board: GSK, Eisai, Basilea Pharmaceutica, iTEOS, Clovis Oncology, Shattuck Labs, AstraZeneca, Regeneron; Financial Interests, Personal, Invited Speaker: GSK, Zydus Cadila, Clovis Oncology, AstraZeneca, GSK; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Other, Membert of Oncology and Haematology Expert Advisory Group: Commission on Human Medicines; Financial Interests, Institutional, Invited Speaker: GSK, Clovis Oncology, Clovis Oncology, Eisai, InCyte, AstraZeneca, MSD, Roche, BerGenBio, Allarity, IoVance, Artios, Regeneron; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.

Oza, A. M., et al. (2022). "Overall survival results from ARIEL4: A phase III study assessing rucaparib vs chemotherapy in patients with advanced, relapsed ovarian carcinoma and a deleterious BRCA1/2 mutation." Annals of Oncology 33(Supplement 7): S780.
	Background: In the primary analysis of ARIEL4 (NCT02855944), rucaparib significantly improved progression-free survival (PFS) vs standard-of-care chemotherapy (CT) in patients (pts) with relapsed, heavily pretreated, BRCA1/2-mutated ovarian carcinoma (Kristeleit et al. Lancet Oncol. 2022;23:465-78). Here, we present final overall survival (OS) and PFS on the subsequent line of therapy (PFS2) results from the intent-to-treat (ITT) population. Method(s): Pts were randomised 2:1 to oral rucaparib 600 mg BID or CT. In the CT group, pts with progression-free interval (PFI) >=1 to <6 months (platinum resistant) or >=6 to <12 months (partially platinum sensitive) received weekly paclitaxel; pts with PFI >=12 months (fully platinum sensitive) received investigator's choice of platinum-based CT (single-agent platinum or platinum doublet). Pts in the CT group could cross over to receive rucaparib upon confirmed radiographic progression per RECIST. OS was a standalone secondary endpoint; PFS2 was an exploratory endpoint. Result(s): At data cutoff, 14/233 (6%) pts in the rucaparib group and 0/116 in the CT group were ongoing on assigned study treatment. Following progression on CT, 80 (69%) pts crossed over to receive rucaparib; overall, 313/349 (90%) pts received rucaparib from randomisation or after crossover. Death events have occurred in 244 (70%) pts. Efficacy endpoints are presented in the Table. Rucaparib safety was consistent with previous reports. [Formula presented] Conclusion(s): PFS2 was not significantly different for pts in the rucaparib or CT groups. In the ITT population, the secondary endpoint of OS favoured CT. Amongst patients with platinum-sensitive disease, OS was similar between the treatment groups; the difference in the ITT population was driven by the platinum-resistant subgroup. OS was confounded by the high rate of crossover, raising important questions about the optimal sequencing of PARP inhibitors in advanced disease. Clinical trial identification: NCT02855944 August 4, 2016. Editorial acknowledgement: Medical writing and editorial support were funded by Clovis Oncology, Inc. and provided by Shelly Lim and Kathleen Blake of Ashfield MedComms, an Ashfield Health company. Legal entity responsible for the study: Clovis Oncology, Inc. Funding(s): Clovis Oncology, Inc. Disclosure: A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline. A.A. Fedenko: Financial Interests, Personal, Invited Speaker: MSD, Amgen; Financial Interests, Personal, Advisory Board: Novartis. A.C. de Melo: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Sanofi; Financial Interests, Institutional, Invited Speaker: Regeneron Pharmaceuticals, Novartis, Merck Sharp and Dohme, GlaxoSmithKline, F. Hoffmann-La Roche, Clovis Oncology, Inc., Bristol-Myers Squibb, AstraZeneca, Amgen. Y. Shparik: Financial Interests, Personal, Other, honoraria: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Other, honoraria: Roche. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, ImmunoGen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de Espana, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann -La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de Espana SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. B. Mackowiak-Matejczyk: Financial Interests, Personal, Invited Speaker, honoraria: AstraZeneca, GlaxoSmithKline, Roche; Financial Interests, Personal, Advisory Board: Seagen, GlaxoSmithKline; Financial Interests, Personal and Institutional, Funding: Clovis Oncology, Inc., AstraZeneca AB, AstraZeneca Pharma Poland sp zoo, MERSANA Therapeutics, MSD Polska Sp zoo, Parexel International Limited, Quiniles Eastern Holdings, Reg eron Pharmaceuticals, Roche Polska sp zoo, Seagen, Tesaro, Tesaro Bio Netherlands BV. D. Thomas: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K.K. LIN: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K. McLachlan: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. S. Goble: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. R. Kristeleit: Financial Interests, Personal, Advisory Board: GSK, Eisai, Basilea Pharmaceutica, iTEOS, Clovis Oncology, Shattuck Labs, AstraZeneca, Regeneron; Financial Interests, Personal, Invited Speaker: GSK, Zydus Cadila, Clovis Oncology, AstraZeneca, GSK; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Other, Membert of Oncology and Haematology Expert Advisory Group: Commission on Human Medicines; Financial Interests, Institutional, Invited Speaker: GSK, Clovis Oncology, Clovis Oncology, Eisai, InCyte, AstraZeneca, MSD, Roche, BerGenBio, Allarity, IoVance, Artios, Regeneron; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Oza, A. M., et al. (2021). "Subgroup analysis of rucaparib versus chemotherapy as treatment for BRCA-mutated, advanced, relapsed ovarian carcinoma: effect of platinum sensitivity in the randomized, phase 3 study ARIEL4."  39(15 SUPPL).
	Background: In ARIEL4 (NCT02855944), rucaparib significantly improved the primary endpoint of progression‐free survival (PFS) vs chemotherapy (CT) in patients with advanced, relapsed ovarian carcinoma (OC) harboring a deleterious BRCA1/2 (BRCA) mutation (median PFS 7.4 [95% CI 7.3‐9.1] vs 5.7 [5.5‐7.3] months; hazard ratio (HR) 0.64 [95% CI 0.49‐0.84]; P=0.001). This prespecified exploratory analysis investigated the effect of platinum sensitivity on the efficacy of rucaparib vs CT in ARIEL4. Methods: Patients were randomized 2:1 to oral rucaparib 600 mg twice daily or CT and stratified based on progression‐free interval (≥1 to <6 months = platinum resistant; ≥6 to <12 months = partially platinum sensitive; ≥12 months = fully platinum sensitive). In the CT group, patients with platinum‐resistant or partially platinumsensitive disease received weekly paclitaxel 60‐ 80 mg/m2 ; patients with fully platinum‐sensitive disease received investigator's choice of platinum‐based CT (single‐agent carboplatin or cisplatin, or platinum doublet). Patients could crossover from CT to rucaparib following radiologic disease progression. Efficacy endpoints were explored in patients with a confirmed BRCA mutation (patients with a reversion mutation were excluded), based on the randomization strata of platinum sensitivity. Results: The visit cutoff date was September 30, 2020. PFS and objective response rates (ORR) per RECIST v1.1 for rucaparib vs CT across subgroups are presented in the Table. The most common treatment‐emergent adverse events in the rucaparib group were anemia/decreased hemoglobin (platinum‐resistant patients: rucaparib 47% vs CT 40%; partially platinumsensitive patients: 63% vs 27%; fully platinumsensitive patients: 58% vs 20%) and nausea (52% vs 21%; 51% vs 23%; 60% vs 68%). In the intent‐to‐treat population, 74/116 (64%) patients in the CT group crossed over to receive rucaparib: 39/59 (66%) with platinum‐resistant, 25/31 (81%) with partially platinum‐sensitive, and 10/26 (38%) with fully platinum‐sensitive disease. Conclusions: Results from this exploratory subgroup analysis suggest that rucaparib is a reasonable treatment option for heavily pretreated patients across all platinum sensitivity subgroups. Safety was consistent with prior rucaparib studies.

Ozbasli, E. and M. Gungor (2022). "Perioperative outcomes of robotic versus laparoscopic sacrocolpopexy." Pelviperineology 41(3): 178-184.
	Objective: To compare the perioperative outcomes of robotic-assisted sacrocolpopexy (RSCP) versus conventional laparoscopic sacrocolpopexy (LSCP). Material(s) and Method(s): A retrospective cohort of 68 patients underwent conventional LSCP or RSCP at Acibadem Maslak University Hospital between May 2010 and June 2019. Data on demographic and surgical characteristics and peri-and postoperative outcomes were examined. The primary outcomes were operative time and postoperative complication rate. The secondary outcomes were postoperative pain score, pre-and postoperative hemoglobin values, body mass index, readmission rate, length of hospital stay, and incidence of intraoperative complication. The Kolmogorov-Smirnov goodness-of-fit test, t-test, Mann-Whitney U test, chi-square test, and Fisher's Exact test were used, and Spearman correlation analysis was performed. Result(s): In total, 68 patients were evaluated (LSCP, n=52; RSCP, n=16). The RSCP group (204.88+/-54.97 min) had a longer operative time than the LSCP group (142.1+/-35.32 min) (p<0.001). The rates of early postoperative complications (such as desaturation, oliguria, and nausea) were 31.3% in the RSCP group and 5.8% in the LSCP group (p=0.015). The postoperative pain scores did not significantly differ between the LSCP group (3.9+/-1.64) and the RSCP group (3.38+/-1.54) (p=0.256). Further, there was no significant difference between the two groups in terms of pre-and postoperative hemoglobin values, demographic characteristics, readmission rate, incidence of intra-and postoperative complications (such as mesh erosion, voiding difficulty, fistula, and recurrence), and length of hospital stay. Conclusion(s): LSCP may be superior to RSCP. However, the surgical route should be individualized based on the surgeon's experience and the clinic's resources.Copyright © 2022 by the International Society for Pelviperineology / Pelviperineology published by Galenos Publishing House.

Ozcan, M. C. H., et al. (2022). "Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review." Women's Health 18.
	Objective: Review the safety of fertility preservation through ovarian stimulation with oocyte or embryo cryopreservation, including cycle and medication options. Evidence review: A systematic review of peer-reviewed sources revealed 2 applicable randomized control trials and 60 cohort studies as well as 20 additional expert opinions or reviews. Result(s): The capacity for future family building is important for the majority of reproductive age people, despite life-altering medical or oncologic diagnosis. Modern fertility preservation generates a high rate of oocyte yield while utilizing protocols that can be started at multiple points in the menstrual cycle and suppressing supra-physiologic levels of estrogen. Finally, more than one quarter of fertility preservation patients will return to later utilize fertility services. Conclusion(s): For most patients, fertility preservation can safely be pursued and completed within 2 weeks without affecting disease severity or long-term survival.Copyright © The Author(s) 2022.

Ozcan, S. and N. Kirca (2023). "Effects of care given in line with Levine's Conservation Model on the quality of life of women receiving infertility treatment: A single blind randomized controlled trial." Health Care for Women International 44(4): 418-439.
	Although infertility is not a life-threatening condition, it decreases the quality of life of people. This single blind randomized controlled trial was conducted with 80 women who received infertility treatment in an IVF Center located in a city center in the west of Turkey between May 2020 and February 2021. It was determined that thanks to the holistic care given in line with Levine's Conservation Model (LCM), fatigue levels of the women in the experimental group decreased, their energy levels increased, their structural, personal and social integrity was conserved and thus their quality of life improved compared to the women in the control group (all p < 0.001).

Ozceltik, G., et al. (2022). "Comparison of perioperative outcomes between colpocleisis with hysterectomy and colpocleisis without hysterectomy." Journal of Gynecology Obstetrics and Human Reproduction 51(9): 102456.
	Study Objective: To evaluate the effect of concomitant hysterectomy on perioperative outcomes in patients who underwent obliterative pelvic organ prolapse (POP) surgery.; Material and Methods: This retrospective study included 95 consecutive patients with no prior hysterectomy who underwent obliterative surgery for POP between February 2015 and April 2021. Perioperative outcomes of colpocleisis without hysterectomy (C) and colpocleisis with hysterectomy (CH) were compared.; Results: Of the 95 patients, 49 (51.6%) underwent C and 46 (48.4%) underwent CH. Patient characteristics including age, body mass index and history of prolapse surgery were comparable between the groups (P-values .367, .199, and .363, respectively). The rate per prolapse stage, from stage 2 to stage 4, was similar in both groups (P-values .709, >.999, and .838 for Stage 2, Stage 3, and Stage 4, respectively). The mean operating time was shorter in the C group than in the CH group (68.9 ± 25.7 minutes versus 94.7 ± 23.1 minutes, P-value < .001). Other perioperative outcomes including postoperative hemoglobin drop, duration of Foley catheter, rate of intraoperative complications, rate of patients with postoperative adverse events, reintervention rate and readmission rate were comparable in both groups (P-values .125, .362, .484, > .999, .495, and > .999, respectively).; Conclusion: CH is associated with a longer operative time compared to C. However, concomitant hysterectomy does not appear to affect perioperative outcomes other than the operative time negatively. (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Özdemir Belma, G. (2024). "Re: "Noncoding RNAs Interplay in Ovarian Cancer Therapy and Drug Resistance" by Liu et al." Cancer biotherapy & radiopharmaceuticals 39(1): 102.
	
Ozdemir, J. and S. Ozcan (2023). "Do postpartum insomnia, fatigue and depression affect the maternal role of primiparous women?" Women & Health: 1-10.
	Many factors negatively affect the motherhood role. Fatigue, insomnia and depression, which are among these factors, have not been investigated together in any study. Therefore, we carried out this study to determine the effect of insomnia, fatigue and depressive symptoms on the motherhood role in primiparous mothers. In this descriptive and cross-sectional study, we included 153 women who met the inclusion criteria using the simple, random sampling method. To determine the independent variables affecting the motherhood role, we used the backward regression model. In this study, we determined that the women's spending more energy while they performed the activities of daily living in the postpartum period, their suffering from insomnia due to baby care and their depressive symptoms affected their motherhood role by 32.6 percent. We also determined that there was a moderately significant relationship between insomnia, fatigue and depressive symptoms in the postpartum period. In particular, because depressive symptoms are the variable most related with the motherhood role (r = -0.520; p < .001), women should be followed-up regularly in the postpartum period from this aspect. It is also important to deal with insomnia in the early postpartum period, because it is a common problem in most women after childbirth.

Ozdemir, Z., et al. (2023). "Determining the Effects of Gynecological Cancers on Women's Quality of Sexual Life." Journal of Ankara University Faculty of Medicine 76(2): 101-107.
	Objectives: The aim of this study is to determine the changes in the sexual life of women undergoing gynecological cancer treatment and to describe the effects of these changes on their quality of sexual life. Material(s) and Method(s): This descriptive study was performed with 101 women diagnosed with endometrial, ovarian, and cervical cancer to determine the changes in the quality of sexual life in Ankara University Faculty of Medicine, Department of Obstetrics and Gynecology. Data were collected by face-to-face interview method using the Descriptive Characteristics Form and Sexual Quality of Life Questionnaire-Female after the women who met the research criteria and agreed to participate in the study read and signed the informed consent form. Result(s): The mean age of the participants was 58.32+/-10.76 years. 96.1% had ovarian cancer, 61.5% had stage 3, and 87.3% received chemotherapy. 49% of them had questions about the changes that may occur in their sexual life during the treatment, and 51% of them had no questions. 13.7% of the reasons for not asking questions were "my other health problems are more important" and 73.5% preferred other (not wanting to explain) reasons. The mean of the scale result was 57.05+/-1.85. Conclusion(s): The quality of sexual life of women with gynecological cancer was moderate. Health professionals should be aware of the sexual problems experienced by women undergoing gynecological cancer treatment and should be able to provide individualized health care.Copyright © Telif Hakki 2023 Ankara Universitesi Tip Fakultesi.

Ozdil, M. (2023). "Postpartum Depression Among Mothers of Infants Hospitalized in the Neonatal Intensive Care Unit During the COVID-19 Pandemic." Cureus 15(8): e44380.
	Background Neonatal intensive care unit (NICU) hospitalization of newborn babies has been shown to have a negative impact on the mental health of postpartum women. The mental health of new mothers may be further burdened by the effects of the coronavirus disease 2019 (COVID-19) pandemic on social, economic, and psychological dimensions. This study aimed to evaluate postpartum depression and related factors in mothers of infants hospitalized in NICU during two distinct COVID-19 pandemic periods and examine any additional effects of the pandemic on the mental health of postpartum women. Methodology The Edinburgh Postpartum Depression Scale (EPDS) was applied to 250 NICU mothers during the COVID-19 pandemic. The first 125 women's children were hospitalized during a period of high number of cases and deaths when restrictions were in place for NICU parental visits (November 2021 to February 2022, the early group). The remaining 125 women completed the scale when there was a lower number of cases and restrictions had been eased (March to June 2022, the late group). Results In the early group, the EPDS scores were statistically higher (7.53.9 vs. 5.63.4; p < 0.001), smoking and NICU stay duration were significantly higher (p = 0.01), whereas the duration of marriage was significantly lower (p = 0.01). Women in the late group with EPDS scores ≥13 were statistically less educated (p = 0.01). EPDS scores ≥13 were significantly associated with depression during pregnancy and with a history of abortion/stillbirth/neonatal death (odds ratio (OR) = 5.240, 95% confidence interval (CI) 1.114 to 27.967, p = 0.03 and OR = 1.641, 95% CI = 1.009 to 2.669, p = 0.04, respectively). Conclusions NICU admission is a significant maternal risk factor for postpartum depression due to the disruption of maternal-infant bonding, and this risk may be exacerbated during times of global public health crises such as the COVID-19 pandemic. Depression during pregnancy and the presence of a perinatal loss may also contribute to worse postpartum mental outcomes in NICU mothers.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Ozdil et al.)

Özel, Y., et al. (2023). "[Comparison of Conventional Methods with Molecular Methods in the Diagnosis of Trichomonas vaginalis and Investigation of Metronidazole Resistance]." Mikrobiyoloji bulteni 57(4): 625-638.
	Trichomoniasis is a sexually transmitted parasitic infection caused by Trichomonas vaginalis. In the diagnosis of trichomoniasis, direct microscopy (DM) is preferred, which is a cheap and fast method, although it has low sensitivity. Culture methods, which are accepted as the gold standard, can only be applied in certain centers due to the need for experienced personnel and the ability to get results within 2-7 days, despite their high sensitivity. In this study, it was aimed to compare conventional microscopic and culture methods used in the routine diagnosis of T.vaginalis with polymerase chain reaction (PCR) method and to investigate ntr4 and/or ntr6 gene polymorphism in the nitroreductase gene region, which are thought to be associated with metronidazole resistance in T.vaginalis strains isolated from clinical specimens. Vaginal swab specimens were collected from the posterior fornix of the vagina with two sterile ecuvion sticks during the gynecological examinations of 200 patients who applied to the Balıkesir University Health Practice and Research Hospital, Obstetrics and Gynecology Polyclinic between March 2019 and August 2021. The first swab sample was used for direct microscopic examination, Giemsa staining and conventional PCR analysis, while the second swab specimen was taken into trypticase-yeast-extract-maltose (TYM) medium for T.vaginalis culture and followed for eight days at 37 °C. All specimens were screened for the presence of T.vaginalis using primers specific to the β-tubulin (btub1) gene region and clinical isolates grown in TYM medium were examined for metronidazole resistance using primers specific for the nitroreductase gene region by using conventional PCR. Drug resistance test was also performed for the isolates in which polymorphism associated with metronidazole resistance was detected. Eight (4%) of 200 patient specimens were found positive by both culture/staining and PCR methods. The mean age of the patients included in the study was 39.9, while the mean age of the patients with positive T.vaginalis was 41.8. The most common clinical findings in the patients were foul-smelling vaginal discharge (36%), groin pain (21%), vaginal itching (19%), and burning sensation during urination (18%). In three out of eight T.vaginalis strains isolated from clinical samples, the presence of polymorphism in the ntr6 gene, which is thought to be associated with metronidazole resistance, was demonstrated by PCR. It was observed that three isolates with ntr6 gene polymorphism were phenotypically resistant to metronidazole (MLK= 390 µM). In this study, the fact that three of eight clinical isolates that were resistant to metronidazole by the broth microdilution method and as well as showing ntr6 gene polymorphism supported the thesis that there might be a close relationship between metronidazole resistance and ntr6 gene polymorphism. As a result, the use of culture and molecular methods in the diagnosis of T.vaginalis, in addition to the microscopy method, may contribute to a more accurate laboratory diagnosis of the agent, to detect metronidazole resistance molecularly and phenotypically, to determine metronidazole resistance rates in our country and to update treatment protocols within the framework of these data.

Ozen, M., et al. (2021). "Primary bilateral ovarian artery embolization for uterine leiomyomatosis in the setting of a rare anatomic variant - hypoplastic uterine arteries." Radiology case reports 16(9): 2426-2428.
	We present the case of a 50-year-old female who underwent bilateral ovarian artery embolization for uterine fibroids in the setting of hypoplastic uterine arteries. Ovarian artery embolization is usually conducted during uterine artery embolization for fibroids to increase the procedure success when ovarian feeders are seen. The bilateral ovarian artery embolization is rarely performed due to fears of amenorrhea and early menopause from decreased blood supply to both ovaries. According to our knowledge, this the first case report describing primary bilateral ovarian artery embolization in the setting of a rare anatomic variant- hypoplastic uterine arteries. The patient had complete resolution of symptoms from her uterine fibroids after treatment with bilateral ovarian artery embolization with no ovarian failure findings on the follow-up.

Ozer, G., et al. (2023). "Factors affecting live birth rates in frozen-thawed single euploid blastocyst transfer cycles." Human Reproduction 38(Supplement 1): i532.
	Study question: What are the factors affecting the rates of live birth in frozen- thawed euploid embryo transfer cycles? Summary answer: Some demographic characteristics, frozen embryo transfer (FET) cycle parameters, and embryo characteristics of patients affect live birth rates in euploid embryo transfer cycles. What is known already: The aim of assisted reproductive techniques (ART) is to achieve live birth as soon as possible. Preimplantation genetic testing (PGT) is an embryo selection technique recommended to shorten the live birth time. In addition, PGT reduces the number of failed ART cycles by eliminating embryos with chromosomal abnormalities that will not implant or will cause miscarriage. Despite these, the live birth rate after euploid embryo transfer cycles is still not at the expected level. Study design, size, duration: This retrospective cohort study was conducted between January 2011 and May 2021 at the IVF and Reproductive Genetics Centre, Memorial Sisli Hospital, Istanbul, Turkey. The study involved a total of 2783 frozen-thawed euploid embryo transfer cycles. Participants/materials, setting, methods: 2873 euploid FET cycles were analysed in the study to determine factors affecting live birth rates. 30 parameters thought to affect live birth were identified and analysed by logistic regression analysis on the effects of live birth. These parameters include patients' demographics, fresh cycle and FET cycle characteristics, and embryo- related parameters on live birth effects in euploid embryo transfer cycles. Main results and the role of chance: 53% of 2783 euploid embryo transfer cycles have resulted in a live birth. The birth rate was 0,5 times less in the group with a body mass index (BMI) of higher than 29 compared to the group with a BMI of less than 25 (p<0.05). In cycles in which embryos of good-tomoderate- to-poor quality were transferred, the chance of live birth was lower than in cycles in which embryos of top quality were transferred (OR:0.837 OR:0.515 OR:0.528, respectively). The live birth rate was higher in cases where endometrial preparation was performed in natural cycles than in artificial cycles (OR:1.67, p<0.05). Embryo transfers without separate blastomeres had a higher live birth rate than embryo transfers with separate blastomeres (OR:1.416, p<0.006). The live birth rate was 0.7 times lower in the group that did not undergo embryo re-expansion 4 hours after thawing (p<0.04). Embryo transfer on the sixth day was associated with a lower live birth rate than embryo transfer on the fifth day. (OR:0.6, p<0.02). The group with a history of recurrent implantation failure (RIF) had a lower live birth rate than the group without a history of RIF (OR:0.5) Limitations, reasons for caution: This study is a retrospective study. Wider implications of the findings: In euploid embryo transfer cycles, clinicians and embryologists must know the parameters affecting live birth to guide treatment and select the embryo to be transferred first. In addition, the patient should be informed and guided about these factors.

Ozer, G., et al. (2021). "Oral dydrogesterone vs. micronized vaginal progesterone gel for luteal phase support in frozen-thawed single blastocyst transfer in good prognosis patients." Journal of Gynecology Obstetrics and Human Reproduction 50(5): 102030.
	Objective: To investigate the efficacy of oral dydrogesterone for luteal phase support (LPS) in modified natural cycle frozen‐thawed embryo transfers (mNC‐FET) compared to micronized vaginal progesterone (MVP) gel. Methods: This was a randomized, single‐center, parallel controlled trial conducted at an ART and Reproductive Genetics Centre within a private hospital between January and August 2019. A total of 134 women, aged below 38, were assigned randomly to receive oral dydrogesterone (n = 67) or MVP (n = 67) for LPS in mNC‐FET. The primary outcome was ongoing pregnancy rate (OPR) and secondary outcomes were clinical pregnancy and miscarriage rates, patients’ satisfaction and tolerability of oral and vaginal progesterone. A questionnaire was developed to compare patient satisfaction and side effect profiles. Results: There was no significant difference in demographic features such as female age, body mass index, AMH levels and fresh cycle characteristics between two groups (p > 0.05). When mNC‐FET outcomes were compared, OPR was 68.7 % in MVP gel group and 71.6 % in the dydrogesterone group respectively percentage difference, ‐2.99; 95 % CI: ‐17.96, 13.10) Biochemical and clinical pregnancy rates and biochemical and clinical miscarriage rates were also similar between two groups. A significantly higher patient tolerability score was present in the dydrogesterone arm (4.09 ± 0.96 vs 3.36 ± 1.23, p = 0.001). Conclusion: Our results suggest that oral dydrogesterone provides similar ongoing pregnancy rates compared to MVP gel as a LPS in mNC FET. Since dydrogesterone is an effective and easy‐to‐use option with fewer intolerable side effects including vaginal irritation, vaginal discharge, and preventing sexual intercourse, it can be used as LPS in mNC FET.

Özerdoğan, N., et al. (2023). "The Effect of Bright White Light on Fatigue Levels in Patients with Gynecological Cancer: A Randomized Control Trial." Journal of palliative care 38(4): 416-423.
	Objectives: Bright white light (BWL) therapy is one of the non-pharmacological methods in the management of fatigue. The aim of the study was to evaluate the effect of BWL on fatigue levels in patients with gynecological cancer who were receiving chemotherapy. Methods: This randomized controlled study were made with 72 women (intervention (n:36) and control (n:36) groups) at gynecologic oncology clinic. Standard BWL at the intensity of 10,000lux was applied to the patients in the intervention group at the same time every day between the second and the eighth days of the chemotherapy cycle. Fatigue levels of all patients (n: 72) were evaluated on the first,ninth and 21st days. Results: The first, ninth, and 21st days general fatigue scores of intervention and control groups was 4.876 ± 0.000;4.384 ± 0.270;4.387 ± 0.258 and 4.876 ± 0.000;5.033 ± 0.270;4.984 ± 0.258, respectively ( p = 0.100). Interference of fatigue with daily life scores was found statistically different between the intervention and control groups in the first, ninth, and 21st day, respectively 4.55 ± 0.26; 3.53 ± 0.23; 3.57 ± 0.22 and 4.95 ± 0.26;4.79 ± 0.23;4.82 ± 0.22 ( p = 0.029). Conclusions: BWL therapy was effective in reducing interference of fatigue with daily life in patients receiving chemotherapy, but did not affect the general fatigue level of the patients. Based on the available data, it is possible that the application of BWL may have a positive effect on general fatigue when the number of samples and the application time are increased. Trial Registration: ClinicalTrials.gov Identifier: NCT05009693.; Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ozsoy-Unubol, T., et al. (2021). "The effect of vitamin D and exercise on balance and fall risk in postmenopausal women: a randomised controlled study." International Journal of Clinical Practice 75(12): e14851.
	Objective: To evaluate the effects of vitamin D and exercise on balance, fall risk and quality of life (QoL) in postmenopausal women. Methods: In this prospective, randomised, controlled, single‐blind study postmenopausal women aged 50‐70�years were included. Participants with <25nmol/L 25(OH) vitamin D were randomised to three groups: group‐I (vitamin D replacement) (n�=�21), group‐II (core and balance exercises) (n�=�18), and group‐III (vitamin D replacement plus core and balance exercises) (n�=�20). The participants with >75nmol/L 25(OH) vitamin D (group‐IV) (n�=�40) were designated as control group and received the core and balance exercises. The participants were evaluated before and after 8�weeks with Berg balance test and Biodex balance system (postural stability and fall risk tests) for balance and Nottingham Health Profile (NHP) for QoL. Results: Group IV had better baseline BBT, NHP pain, NHP emotional reactions, NHP social isolation subdomain and total score. After treatment, all groups showed significant improvement in balance (except group I, mediolateral stability index) and QoL (except group II). There was no significant difference between groups (I, II and III) after intervention. Conclusion: Vitamin D replacement therapy has positive effects on balance and QoL. Core strengthening and balance exercises are essential for better balance and fall prevention in postmenopausal women. Any superior effect of vitamin D or exercise on each other was not determined.

Öztürk, B., et al. (2022). "Clinical outcomes and survival following treatment of bone metastases from uterine leiomyosarcoma: A report of 6 cases." Acta orthopaedica et traumatologica turcica 56(4): 278-282.
	Objective: This study aimed to analyze the patient-reported outcomes and survival following surgical treatment of bone metastases from (uLMS) uterine leiomyosarcoma.; Methods: A retrospective review of six patients undergoing surgical procedures for metastatic uLMS over seven years was conducted at a single center. All patients were reviewed for their primary malignancy and characteristics of bone metastasis during follow-up. Clinical presentation of bone metastasis, modality, and the type of treatment related to musculoskeletal involvement were also analyzed. The visual analog pain scale (VAS) and Eastern Cooperative Oncology Group (ECOG) performance status scale were used pre-and postoperatively to evaluate the patient-reported outcome.; Results: Four patients had solitary bone metastases, whereas multiple bone metastases were diagnosed in two. Of those who had solitary bone metastasis, all of them were treated with wide resection. One of the two patients with multiple bone metastases was also treated with wide resection, and the other was treated with intralesional curettage. Four patients died from primary disease, and two were alive without evidence of disease recurrence. The median survival time following a diagnosis of bone metastasis was 15.0 months (95% CI, 0.6 to 29.4 months). The mean VAS scores for all six patients improved. However, the improvement in ECOG performance status was seen in only four patients.; Conclusion: Although the prognosis of uLMS patients with bone metastasis seems poor, wide resection of the solitary bone metastasis may help prolong the overall survival. Performing orthopedic surgeries for the bone metastasis from uLMS in case of intractable pain after palliative radiotherapy, impending or pathological fracture, or solitary disease has been shown to decrease the pain significantly and improve the performance status in the majority.; Level of Evidence: Level IV, Therapeutic Study.

Ozturk, N., et al. (2023). "The effect of abdominal massage and stretching exercise on pain and dysmenorrhea symptoms in female university students: A single-blind randomized-controlled clinical trial." Health Care for Women International 44(5): 621-638.
	In this study the researchers aimed to determine the effect of abdominal massage and stretching exercises on the severity of pain, dysmenorrhea symptoms and menstrual blood lost in university students. In this single-blind randomized controlled clinical trial 63 university students were included. Participants were randomly assigned into massage group, exercise and control groups. Our findings showed that the 2 nd cycle scores related to abdominal-back pain and fatigue in the massage group and 2 nd cycle scores related to mood change in the exercise group were significantly lower than those of the massage and control groups. However, there was no difference between groups in terms of the Visual Analogue Scale scores and blood lost. Our evidence indicates that massage was effective on abdominal-back pain and weakness, and exercise was effective on mood change.

p6g3t, R. B. R. (2023). "Evaluation of pelvic floor muscle function after clinical surgery or surgery associated with cystopexy to control urinary loss." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: E02.831.535 This is a randomized, controlled, parallel, blind clinical trial. It will consist of two groups, the comparator group (CG) and the pelvic floor muscle training group (GTMPAP), each group will consist of 16 women, with urinary incontinence and prolapse up to grade II, with no surgery history to correct the previous urinary loss. The GC will only receive information on the educational content carried out on a single day along with the initial assessment. The GTMPAP will perform twice a week, individually, in 16 sessions and each session will provide health education on topics involving urinary incontinence. CONDITION: C23.300.842.624 Urinary Incontinence; Cystocele; Exercício Pré‐Operatório; Pelvic Floor PRIMARY OUTCOME: Functionality measured by vaginal manometry SECONDARY OUTCOME: Degree of satisfaction assessed by the Patient Global Impression of Change Pelvic floor muscle strength measured by the Modified Oxford Scale Quality of life measured by the World Health Organization Quality of Life Sexual function assessed by the Function Sexual Female Index Stress urinary incontinence using the International Consultation on Incontinence Questionnaire ‐ Short Form Symptoms of pelvic floor disorders using the Pelvic Floor Distress Inventory Symptoms of urgency by the International Consultation on Incontinence Questionnaire Overactive Bladder INCLUSION CRITERIA: Age between 18 and 65 years; no historic of surgery for urinary incontinence and correction of anterior prolapse; no historic of hysterectomy;

p6t4br, R. B. R. (2023). "The Effect of Osteopathy on Women with Chronic Pelvic Pain." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: This research will be a randomized controlled, single‐blind, pragmatic clinical trial. In this study, two osteopaths and two physiotherapists will be responsible for the interventions and will not be blinded to the procedures to be performed. However, they will be blinded to the application of the EVA and SF‐36 instruments, which will be carried out by two undergraduate students, involved in the research, who will be properly trained for this task and blinded to the allocation of participants. The statistician will be blinded to the allocation of participants. The sample will be made up of women between 18 and 50 years old diagnosed with CPP, carried out by the gynecologist, Dr. Rodrigo Vianna in his office located at Av 7, 317/1307, Santa Rosa, Niterói‐ RJ, 24230‐25 and also selected in the gynecology and obstetrics outpatient clinic at Hospital Universitário Antônio Pedro (HUAP), located at Rua Marquês de Paraná, 303 – Centro, Niterói‐RJ, 24033‐900. To identify the sample size (n) necessary to achieve adequate quality to use the ANOVA method, the use of the F test will be considered at the significance level a = 0.05 (5%); the power of the F test of the one‐way ANOVA at level (1 ‐ ß) = 0.85 (85%); the effect size f equals 0.50 (relationship between the standard deviation of the effect to be tested and the standard deviation within the groups involved in the treatments); number of groups k = 2 (both treatments); the number of repeated measurements = 3 (one before, another at the end of the 10 weeks of intervention and another 30 days after the end of the intervention to assess the maintenance of quality of life and the correction of sphericity e = 1 (assuming that there is no violation of sphericity). Thus, using the G*Power software version 3.1.9.7 (FAUL et al, 2007) CONDITION: C23.888.592.612.944 Pelvic Pain PRIMARY OUTCOME: To evaluate the variation in VAS and quality of life after 10 weeks of intervention with Osteopathic Manipulative Treatment compared to Therapeutic Exercises SECONDARY OUTCOME: Evaluate and compare the intensity of pain and quality of life within the group INCLUSION CRITERIA: Women between 18 and 50 years old; diagnosed with Chronic Pelvic Pain for at least 6 months; with Visual Analogue Pain Scale equal to or greater than 4

P, N., et al. (2023). "Oteseconazole for RVVC in diabetes: post-hoc analysis of safety and clinical response in phase 3 studies." American Journal of Obstetrics and Gynecology 228(2 Supplement): S784.
	Objective: WHO forecasts >629 million adults will have diabetes by 2045. Diabetics are more susceptible to yeast overgrowth due to weakened immune systems and immune alternations. Oteseconazole, a novel oral agent that selectively inhibits fungal CYP51, is highly active against Candida albicans, including fluconazole-resistant C. albicans and other Candida species that cause vulvovaginal candidiasis (VVC). Study Design: Two global, randomized, double-blind, phase 3 trials studied oteseconazole in recurrent VVC (RVVC). Eligible participants, presented with acute infection at screening, positive KOH test, and signs and symptoms score >=3, were treated with 3 doses 150-mg fluconazole every 72 hours. If signs and symptoms resolved to 30. Five were insulin dependent. The predominant colonizing organism was C. albicans (n=7), followed by C. glabrata (n=2) and C. parapsilosis (n=1). All 10 participants remained free of acute VVC for the 48-week period and did not report any treatment-related AEs by investigators. Conclusion(s): With the projected increases in diabetes worldwide and VVC infection rates in women with diabetes, oteseconazole is a promising new therapy for diabetic women living with RVVC Disclosure: Yes, this is sponsored by industry/sponsor: Mycovia Pharmaceuticals Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Mycovia PharmaceuticalsCopyright © 2022

Pablo, H.-L., et al. (2022). "Is the combination of exercise and education more effective than exercise alone or education alone in the treatment of non-specific low back pain or pelvic pain in pregnant women?" PROSPERO International prospective register of systematic reviews.
	Review question The PICO question was then chosen as follows: P – population: pregnant women with non-specific low back pain or pelvic pain; I – intervention: exercise therapy plus health education; C – control: only exercise therapy or only health education; O – outcome: characteristics of pain, disability and kinesophobia; S – study designs: randomized controlled trial. Searches Publications of the last ten years in PubMed, Web of Science, PEDro and Cochrane databases. Types of study to be included Included: Randomized Clinical Trials. Excluded: Observational studies, systematic reviews, meta-analyses, narrative reviews and editorials. Condition or domain being studied Low back pain(LBP) and pelvic girdle pain(PGP) are widespread problems of pregnancy, and, when not differentiated, are commonly labeled “lumbopelvic pain.” Pregnancy-related lumbopelvic pain accounts for the majority of sick leave among pregnant women is reported to be a worldwide problem, irrespective of the socioeconomic conditions of the countries. It is estimated that 20%-25% of all pregnant women have lumbopelvic pain sufficiently severe to cause them to seek medical help.The etiology and pathogenesis of pregnancy-related PGP are unclear and probably multifactorial. The most common hypothesis for the development of PGP is a combination of hormonal and biomechanical factors. Motor control patterns in people with PGP have been examined in recent studies, and an alteration in the strategy for lumbopelvic stabilization is suggested to disrupt load transfer through the pelvis. Studies indicate that physical fitness exercises before pregnancy might reduce the risk of developing LBP during pregnancy. Participants/population Pregnant women with non-specific low back pain or pelvic girdle pain. Intervention(s), exposure(s) Specific exercise methods (yoga, pilates, back school, aerobic, functional exercises...) and specific health education methods (ergonomics, healthy living tips, cognitive behavioural therapy, educational interventions...). Comparator(s)/control The experimental group had to be compared to a group that received only exercise or only education. Main outcome(s) The study outcome are pain. Additional outcome(s) The study additional outcomes disability and kinesiophobia. Data extraction (selection and coding) After screening the data, extracting, obtaining and screening the titles and abstracts for inclusion criteria, the selected abstracts were obtained in full texts. Titles and abstracts lacking sufficient information regarding inclusion criteria were also obtained as full texts. Full text articles were selected in case of compliance with inclusion criteria by the two reviewers using a data extraction form. The two authors independently collected the following data from the included articles for further analysis: demographic information (title, authors, journal and year), study-specific parameter (study type, number of treated patients, duration of intervention, number of sessions, techniques of physical therapy included in the intervention, follow-up and drop-out), variables analyzed and instruments of assessment employed. Risk of bias (quality) assessment The Jadad scale and PEDro scale were used to assess the high quality of studies. Strategy for data synthesis The researchers pooled and wrote the data extracted from the results analysis. During the analysis of the analyzed studies, both researchers will use an Excel sheet that, later, they will be able to share and will be the content of the Results section of the systematic review. Standardized mean differences (SMD) and their 95% confidence interval (CI) were calculated as the between-group difference in means divided by the pooled standard deviation (SD), using the Hedges’ g corrected effect sizes. When these data were not available in the study they were requested via email to the authors. SMDs were interpreted using the following cut-off values: 0 to 0.2: very small; from 0.2 to 0.5: small; from 0.5 to 0.8: moderate; and from 0.8: strong. The same increments were used for negative values. Significance level was set to p < 0.05. The I² statistic was utilized to determine the degree of heterogeneity, where the percentages quantified the magnitude of heterogeneity: 25% = low; 50% = medium; and 75% = high heterogeneity. Analyses were performed with Comprehensive Meta-Analysis V2 software (Biostat, NJ). Analysis of subgroups or subsets It was classified and analysed according to the area of back pain (low back pain, pelvic pain). Contact details for further information Pablo Hernandez Lucas phernandez@uvigo.es Organisational affiliation of the review Universidade de Vigo Review team members and their organisational affiliations [1 change] Professor Pablo Hernandez-Lucas. University of Vigo Helena Aguacil Gomez. University of San Jorge Olatz Echeverría. University of San Jorge Dr Raquel Leirós Rodriguez. University of Leon Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 25 March 2022 Anticipated completion date [1 change] 14 February 2023 Funding sources/sponsors Non funding Conflicts of interest Language English Country Spain Stage of review [1 change] Review Completed not published Subject index terms status Subject indexing assigned by CRD Subject index terms Exercise Therapy; Female; Humans; Low Back Pain; Pelvic Pain; Pregnancy; Pregnant Women Date of registration in PROSPERO 02 May 2022 Date of first submission 01 April 2022

Pabuccu, A. P. E., et al. (2021). "Follicular flushing using double lumen needle yields more oocytes in mono-follicular poor responders." Journal of Gynecology Obstetrics and Human Reproduction 50(9): 102150.
	Objective: To compare the efficacy of follicular flushing (FF) with double lumen needle and direct follicular aspiration with single lumen needle in terms of oocyte yield in mono-follicular responder patients undergoing assisted reproduction techniques (ART). Material(s) and Method(s): Prospective 'quasi-experimental' study was carried out in an IVF center. Infertile women 18-42 years of age with diminished ovarian reserve who revealed a single follicle >17 mm on the day of oocyte retrieval were included in the study. Follicular flushing up to 8 times was performed in FF group using an 17-G double lumen needle. Direct follicular aspiration using a 17-G single lumen needle without FF was performed in direct aspiration group. Total numbers of collected oocytes, metaphase 2 oocytes, fertilization and pregnancy rates were compared among groups. Result(s): A total of 206 women underwent oocyte retrieval procedure; 106 women were assigned to FF and 100 women into direct aspiration arm. Overall oocyte retrieval rate was 50.4% in all cases. The total oocyte retrieval rate was higher (65/106, 61.9%) in FF group, than in direct aspiration group (39/100, 39%, p = 0.001). Metaphase 2 oocyte rate was also higher in FF group (47/106, 44.3% vs 29/100, 29% p = 0.04). Fertilization rates, total number of patients with a cleavage stage embryo and grade 1 cleavage embryo were similar among the groups (p>0.5). Numbers of positive hCG, ongoing pregnancy and miscarriage rates were similar among groups. Conclusion(s): Follicular flushing using double lumen needle in mono-follicular responder patients with diminished ovarian reserve yields more oocytes and mature oocytes than direct aspiration of follicles.Copyright © 2021 Elsevier Masson SAS

Pacheco, F., et al. (2021). "Efficacy of non-invasive brain stimulation in decreasing depression symptoms during the peripartum period: A systematic review." Journal of Psychiatric Research 140: 443-460.
	Background: Non-invasive brain stimulation (NIBS) techniques have been suggested as alternative treatments to decrease depression symptoms during the perinatal period. These include brain stimulation techniques that do not require surgery and that are nonpharmacological and non-psychotherapeutic. NIBS with evidence of antidepressant effects include repetitive transcranial magnetic stimulation (rTMS), transcranial electric stimulation (TES) and electroconvulsive therapy (ECT). Objective(s): This systematic review aims to summarize evidence on NIBS efficacy, safety and acceptability in treating peripartum depression (PPD). Method(s): We included randomized, non-randomized and case reports, that used NIBS during pregnancy and the postpartum. The reduction of depressive symptoms and neonatal safety were the primary and co-primary outcomes, respectively. Result(s): rTMS shows promising results for the treatment of PPD, with clinically significant decreases in depressive symptoms between baseline and end of treatment and overall good acceptability. Although the safety profile for rTMS is adequate in the postpartum, caution is warranted during pregnancy. In TES, evidence on efficacy derives mostly from single-arm studies, compromising the encouraging findings. Further investigation is necessary concerning ECT, as clinical practice relies on clinical experience and is only described in low-quality case-reports. Limitation(s): The reduced number of controlled studies, the lack of complete datasets and the serious/high risk of bias of the reports warrant cautious interpretations. Conclusions and implications: Existing evidence is limited across NIBS techniques; comparative studies are lacking, and standard stimulation parameters are yet to be established. Although rTMS benefits from the most robust research, future multicenter randomized clinical trials are needed to determine the position of each NIBS strategy within the pathways of care.Copyright © 2021 The Author(s)

Pactr (2021). "Pelvic Floor Rehabilitation in Treatment of Mixed Urinary Incontinence Among Women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Anogenital neuromodulation biofeedback assisted pelvic floor muscle training with electrical stimulation no control group posterior tibial neuromodulation CONDITION: ; Urological and Genital Diseases Urological and Genital Diseases PRIMARY OUTCOME: Subjective outcome measures (questionnaires) SECONDARY OUTCOME: objective measures (clinical examination, manometric pressure measurements). INCLUSION CRITERIA: Idiopathic mixed urinary incontinence age above 18‐year‐old

Pactr (2021). "Povidone Iodine vaginal cleansing trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Postoperative vaginal cleansing group Preoperative vaginal cleansing CONDITION: ; Pregnancy and Childbirth ; Postoperative infectious morbidity Postoperative infectious morbidity Pregnancy and Childbirth PRIMARY OUTCOME: The primary outcome measure was post caesarean endometritis SECONDARY OUTCOME: Post‐caesarean wound infection ; Postoperative fever ; Duration of hospitalisation due to infectious morbidity. ; Adverse reaction to povidone iodine ; INCLUSION CRITERIA: All consented parturient Undergoing elective or emergency caesarean section After the age of fetal viability (= 28weeks gestational age).

Pactr (2021). "Traditional clomiphene citrate with phytoestrogen vs traditional clomiphene citrate vs stair step protocol in patients with polycystic ovaries: a randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Traditional clomiphene phytoestrogen Stair step clomiphene citrate phytoestrogen Traditional CONDITION: Fertility‐female ; Fertility‐female PRIMARY OUTCOME: Endometrial thickness at the day of hCG trigger SECONDARY OUTCOME: Multiple pregnancy rate Clinical pregnancy rate Ovarian hyperstimulation syndrome rate INCLUSION CRITERIA: Age: 25‐30 years Primary infertility due to PCO (Rotterdam criteria 2003) No medical disorders No other causes of infertility

Pactr (2022). "Effect of structured Educational Sessions Regarding Lifestyle Modification on Health-Related Quality of Life among Women with Polycystic Ovary Syndrome: randomized controlled trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group educational group CONDITION: ; Fertility‐female Fertility‐female PRIMARY OUTCOME: 1‐ Evaluate the effect of lifestyle modification program on quality of life among women with PCOS. SECONDARY OUTCOME: Determine the effects of lifestyle interventions on anthropometric and clinical parameters in women with PCOS. INCLUSION CRITERIA: women aged 18‐ 45 years and b) diagnosed with PCOS according to Rotterdam criteria

Pactr (2022). "Impact of adding high probiotic food supplements to the diet and yoga on insulin resistance in polycystic ovarian syndrome." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: control group Mediterranean diet with adding High probiotic food supplements CONDITION: ; Polycystic ovary syndrome Polycystic ovary syndrome PRIMARY OUTCOME: HOMA‐IR for insulin resistance SECONDARY OUTCOME: Serum insulin INCLUSION CRITERIA: • Diagnosis of PCOS which requiring two of three features: anovulation or oligo‐ovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM) seen on ultrasound. • Indicators of insulin resistance including HOMA‐IR, serum insulin and fasting blood sugar (FBS) • physical activity level is 1.2 as they will be chosen Sedentary (little or no exercise)

Pactr (2022). "Novel Vacuum-Induced Hemorrhage Control for Postpartum Hemorrhage: a Multicenter Randomized Trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Standard care Jada System CONDITION: Pregnancy and Childbirth ; Pregnancy and Childbirth PRIMARY OUTCOME: Maternal survival without surgical intervention. SECONDARY OUTCOME: Additional uterotonic used after randomization Estimated blood loss post‐randomization Incremental cost per quality‐adjusted life‐year Composite adverse events potentially related to the Jada System, including genital tract injury, uterine perforation or rupture and endometritis. Maternal death postpartum ; Surgical procedures performed, including uterine vascular ligation, uterine compression sutures and hysterectomy. ; Time from randomization to control of bleeding ; ; Patient satisfaction score on a scale of 0 (least satisfied) to 10 (most satisfied) Number of units of blood products transfused ; Postpartum hemoglobin ; Quality‐adjusted Life‐year based on the literature and Quality of Life Questionnaire (EQ‐5D‐5L) Change in hemoglobin from labor admission to postpartum day 1 ; Maternal transfusion of blood or blood products postpartum ; INCLUSION CRITERIA: 1. 18 years or older 2. Delivery at 34 weeks or greater 3. Vaginal or cesarean delivery 4. Cumulative blood loss>1000ml within 24 after delivery 5. Uterine atony 6. Receipt of first‐line uterotonics 7. Cervix at least 3 cm dilated at cesarean section

Pactr (2022). "Perineal Massage During The Second Stage Of Labour For Preventing Perineal Trauma In Nulliparous Women: a Randomised Controlled Study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Lubricated perineal massage standard of care CONDITION: ; perineal trauma perineal trauma PRIMARY OUTCOME: Proportion of participants having perineal tears during vaginal delivery between the intervention and control groups SECONDARY OUTCOME: Duration of second stage of labour between the two groups Neonatal birth weights, 1st and 5th minute Apgar scores between the intervention and control groups Perineal pain and its severity between the intervention and control groups Proportion of participants having episiotomy during vaginal delivery between the intervention and control groups INCLUSION CRITERIA: 1. Nulliparous women in the age bracket of 18 to 35years 2. Gestational age 37‐42weeks 3. Singleton fetus 4. Cephalic presentation 5. Cervical Os dilatation of 10 cm

Pactr (2022). "Psycho-social support for prevention of perinatal depression." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Group based psychoeducation Focused antenatal care...no any intervention given for mothers on MCH for PPD. CONDITION: Mental and Behavioural Disorders ; Mental and Behavioural Disorders ; Pregnancy and Childbirth Pregnancy and Childbirth PRIMARY OUTCOME: Proportion of mothers who have good social support, post‐partum depression literacy, and low post‐natal depression at ‐6‐weeks post‐partum period. SECONDARY OUTCOME: improvements in utilization of preventive maternal and child health care service, healthy life style of the mother and good birth outcome will be the secondary outcome variable. INCLUSION CRITERIA: Study participant screening will pass two stage; first mothers gestational age will be assessed (calculated based on their last normal menstrual period (LMNP) and fundal height (combination result will be taken) or directly taken from the card. Then mothers whose gestational age 12‐20 weeks will be assessed for their depression status by locally validated tool, patient health questioner‐9 (PHQ‐9)(Yitbarek Kidane Woldetensay, 2018). Mothers who are normal (score 0‐4) and mild (score 5‐9) by PHQ‐9 will be included in the study. The rest with moderate‐severe depression (PHQ‐9=10) in both groups will be referred to nearby hospital psychiatric out patient department, to be further evaluated and treated by district clinician(psychiatrist).

Pactr (2022). "RECTAL DICLOFENAC VERSUS PARACERVICAL BLOCK AS PAIN RELIEF DURING MANUAL VACUUM ASPIRATION: AN OPEN-LABEL RANDOMISED TRIAL." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Plain lignocaine Rectal diclofenac CONDITION: Pregnancy and Childbirth ; Pregnancy and Childbirth PRIMARY OUTCOME: Median pain scores for the two forms of analgesics SECONDARY OUTCOME: Patient Satisfaction with assigned analgesic ; Side effect profile of each analgesic agent INCLUSION CRITERIA: Missed miscarriage Inevitable miscarriage Incomplete miscarriage Anembryonic gestation

Pactr (2022). "respiratory muscles strength and urinary incontinence in patients with urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: inspiratory muscle training none CONDITION: ; Respiratory ; Urological and Genital Diseases Respiratory Urological and Genital Diseases PRIMARY OUTCOME: we hypothesize that inspiratory muscle training strengthens the pelvic floor muscles and improves urinary continence SECONDARY OUTCOME: we hypothesize that inspiratory muscle training is a new strategy to reduce urinary incontinence INCLUSION CRITERIA: urinary incontinence age between 35 and 60 years old

Pactr (2023). "Urodynamic impact of pulsed electromagnetic field therapy (PEMFT) on the neurogenic overactive bladder after partial spinal cord injury: a randomized controlled study." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: CONDITION: ; Nervous System Diseases PRIMARY OUTCOME: Urodynamic and flowmetry test:; •Urodynamic Dantic 5000/5500. The urodynamic investigation system and voiding cytometry were used to carry out the urodynamic examination. ; •The urodynamic machine is a trolley‐mounted equipment with an integrated printer and display.; • A transportable patient unit that includes built‐in H2O and CO2 pumps, a standard‐mounted uroflow transducer, and a standard‐mounted puller mechanism.; ; SECONDARY OUTCOME: Revised Urinary Incontinence Scale (RUIS). ; • The revised urinary incontinence scale includes both questions from the incontinence severity index. The revised urinary incontinence scale is a valid and reliable scale used to assess the severity of incontinence ; INCLUSION CRITERIA: neurogenic overactive bladder due to a partial lesion of the spinal cord above T12 from more than 6 months based on both clinical assessment and radiological investigations of the spine including Computed Tomography (C.T scan) and/or Magnetic Resonance Imaging (MRI)

Padhi, S., et al. (2023). "Comparison of Acute Gastrointestinal Toxicity of Intensity-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiotherapy in Patients of Carcinoma Cervix." Cureus 15(11): e48876.
	Introduction Cervical cancer is the most common gynaecological malignancy worldwide, with a higher prevalence in middle- and low-income countries. Chemoradiotherapy, followed by intracavitary brachytherapy, is the treatment of choice in locally advanced cervical cancer. The most common acute side effect of external beam radiotherapy (EBRT) is bowel toxicity in the form of diarrhoea and abdominal cramps. The treatment techniques of EBRT were revolutionised with the advent of intensity modulation. This study aims to prospectively analyse whether the dosimetric advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3DCRT) is translated clinically into a decrease in acute toxicity. Method Twenty-four patients were randomised into two groups: the 3DCRT and the IMRT. Acute gastrointestinal (GI) toxicity was assessed during treatment using radiation therapy oncology group grading. The factors under consideration were age, stage of the disease, treatment technique, chemotherapy, and the intention of therapy (radical or adjuvant). The mean bowel bag dose of the two techniques was analysed. Result Among the factors under consideration, it was found that the treatment technique was the only factor that had a significant association with acute bowel toxicity in both univariate (p = 0.036) and multivariate analyses (p = 0.028). The mean V25 (the volume receiving 25 Gy), V45, and V50 of the bowel bag in the IMRT arm were significantly less than the 3DCRT arm. Grades 2 and 3 acute bowel toxicities were also higher in the 3DCRT arm. Conclusion The treatment technique is essential to determining acute GI toxicity during pelvic radiotherapy. With IMRT, the dose to the bowel bag and, in turn, the acute bowel toxicity can be reduced.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Padhi et al.)

Padron, A., et al. (2022). "Impacts of Cognitive Behavioral Therapy for Insomnia and Pain on Sleep in Women with Gynecologic Malignancies: A Randomized Controlled Trial." Behavioral sleep medicine 20(4): 460-476.
	Insomnia is an adverse cancer outcome impacting mood, pain, quality of life, and mortality in cancer patients. Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for diverse psychophysiological disorders, including pain and insomnia. Primarily studied in breast cancer, there is limited research on CBT within gynecology oncology. This study examined CBT effects on subjective and behavioral sleep outcomes: Sleep Efficiency (SE), Sleep Quality (SQ), Total Wake Time (TWT), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO). Thirty-five women with insomnia status/post-surgery for gynecologic cancer were randomized to CBT for insomnia and pain (CBTi.p., N = 18) or Psychoeducation ( N = 17). Sleep was assessed via sleep diaries and wrist-worn actigraphy at baseline (T1), post-intervention (T2), and two-month follow-up (T3). Intent-to-treat analyses utilizing mixed linear modeling examined longitudinal group differences on sleep controlling for age and advanced cancer. All participants demonstrated improved (1) subjective SE (0.5, p < .01), SOL (-1.2, p < .01), TWT (-1.2, p < .01), and (2) behavioral SE (0.1, p = .02), TWT (-1.2, p = .03), WASO (-0.8, p < .01) across time. Group-level time trends were indicative of higher subjective SE (6.8, p = .02), lower TWT (-40.3, p = .01), and lower SOL (-13.0, p = .05) in CBTi.p. compared to Psychoeducation. Supplemental analyses examining clinical significance and acute treatment effects demonstrated clinical improvements in SE (T1), TWT (T2, T3), and SOL (T3). Remaining effects were not significant. Despite lacking power to detect interaction effects, CBTi.p. clinically improved sleep in women with gynecologic cancers and insomnia during the active treatment phase. Future research will focus on developing larger trials within underserved populations.

Paes, M. F., et al. (2023). "Overexpression of CLDN16 in ovarian cancer is modulated by PI3K and PKC pathways." Experimental Cell Research 426(2): 113523.
	Epithelial ovarian cancer (EOC) is the gynecological malignant tumor of poorest prognosis and higher mortality rate. Chemotherapy is the base of high-grade serous ovarian cancer (HGSOC) treatment; however, it favors the emergence of chemoresistance and metastasis. Thus, there is an urge to search for new therapeutic targets, such as proteins related to cellular proliferation and invasion. Herein, we investigated the expression profile of claudin-16 (CLDN16 protein and CLDN16 transcript) and its possible functions in EOC. In silico analysis of CLDN16 expression profile was performed using data extracted from GENT2 and GEPIA2 platforms. A retrospective study was carried out with 55 patients to evaluate the expression of CLDN16. The samples were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, molecular docking, sequencing, and immunoblotting assays. Statistical analyzes were performed using Kaplan-Meier curves, one-way ANOVA, Turkey posttest. Data were analyzed using GraphPad Prism 8.0. In silico experiments showed that CLDN16 is overexpressed in EOC. 80.0% of all EOC types overexpressed CLDN16, of which in 87% of the cases the protein is restricted to cellular cytoplasm. CLDN16 expression was not related to tumor stage, tumor cells differentiation status, tumor responsiveness to cisplatin, or patients' survival rate. When compared to data obtained from in silico analysis regarding EOC stage and degree of differentiation, differences were found in the former but not in the later, neither in survival curves. CLDN16 expression in HGSOC OVCAR-3 cells increased by 1.95-fold (p < 0.001), 2.32-fold (p < 0.001), and 6.57-fold (p < 0.001) via PKC, PI3K, and estrogen pathways, respectively. Altogether, our results suggest that despite the low number of samples included in our in vitro studies, adding to the expression profile findings, we provided a comprehensive study of CLDN16 expression in EOC. Therefore, we hypothesize that CLDN16 is a potential target in the diagnosis and treatment of the disease.Copyright © 2023

Páez-Canro, C., et al. (2019). "Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women." The Cochrane Database of Systematic Reviews 1: CD010871.
	Background: The genital infection caused by Chlamydia trachomatis (CT) is a common sexually transmitted infection (STI) globally. The infection is mainly asymptomatic in women, thus it can produce infertility and chronic pelvic pain. In men infection is mainly symptomatic, but can evolve to prostatitis. Clinical practice guidelines for CT urogenital infections do not give any specific recommendation about which antibiotic use as first option OBJECTIVES: To assess the efficacy and safety of antibiotic treatment for CT genital infection in men and non-pregnant women.; Search Methods: The Cochrane Sexually Transmitted Infections' (STI) Information Specialist developed the electronic searches in electronic databases (CENTRAL, MEDLINE, Embase and LILACS), and trials registers. We searched studies published from inception to June 2018.; Selection Criteria: We included parallel, randomised controlled trials (RCTs) of men, and sexually-active, non-pregnant women with CT infection (urethritis or uterine cervicitis or asymptomatic), diagnosed by cell culture for CT, nucleic acid amplification tests (NAAT) or antigen-based detection methods, who had been treated with any of the antibiotic regimens recommended by any of the updated to 2013 CT Guidelines.; Data Collection and Analysis: Four review authors screened evidence according to selection criteria and independently extracted data and assessed risk of bias. Two authors developed the 'Summary of findings' tables. We used a fixed-effect meta-analysis model for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect. We estimated the pooled risk ratio in order to establish the effects of the comparisons. Our primary outcomes were microbiological failure and adverse events, and our secondary outcomes were clinical failure, antimicrobial resistance and reinfection.; Main Results: We selected 14 studies ( 2715 participants: 2147 (79.08%) men and 568 (20.92%) women). The studies were conducted mainly at STD clinics. Sample sizes ranged from 71 to 606 participants; follow-up was 29.7 days on average.For the comparison: azithromycin single dose versus doxycycline once or twice daily for 7 days, in men treated for CT, the risk of microbiological failure was higher in the azithromycin group (RR 2.45, 95% CI 1.36 to 4.41; participants = 821; studies = 9; moderate-quality evidence), but regarding clinical failure, the results showed that the effect is uncertain (RR 0.94, 95% CI 0.43 to 2,05; I² = 55%; participants = 525; studies = 3; low-quality evidence). Regarding adverse events (AE) in men there could be little or no difference between the antibiotics (RR 0.83, 95% CI 0.67 to 1.02; participants = 1424; studies = 6; low-quality evidence). About women treated for CT, the effect on microbiological failure was uncertain (RR = 1.71, 95% CI 0.48 to 6.16; participants = 338; studies = 5; very low-quality evidence). There were no studies assessing clinical failure or adverse events in women, however, we found that azithromycin probably has fewer adverse events in both genders (RR 0.83, 95% CI 0.71 to 0.98; I² = 0%; participants = 2261; studies = 9; moderate-quality evidence).For the second comparison: doxycycline compared to ofloxacin, for men treated for CT the effect on microbiological failure was uncertain (RR 8.53, 95% CI 0.43 to 167.38, I² not applicable; participants = 80; studies = 2; very low-quality evidence), as also it was on clinical failure (RR 0.85, 95% CI 0.28 to 2.62; participants = 36; studies = 1; very low-quality evidence). The effect of in women on clinical failure was uncertain (RR 0.94, 95% CI 0.39 to 2.25; I² = 39%; participants = 127; studies = 2; very low-quality evidence).Regarding adverse events, the effect in both men and women was uncertain (RR 1.02 95% CI 0.66 to 1.55; participants = 339 studies = 3; very low-quality evidence). The effect on microbiological failure in women and in men and women together, the effect on microbiological failure was not estimable. The most frequently AE reported were n t serious and of gastrointestinal origin.No studies assessed antimicrobial resistance or reinfection in either comparison.; Authors' Conclusions: In men, regimens with azithromycin are probably less effective than doxycycline for microbiological failure, however, there might be little or no difference for clinical failure. For women, we are uncertain whether azithromycin compared to doxycycline increases the risk of microbiological failure. Azithromycin probably slightly reduces adverse events compared to doxycycline in men and women together but may have little difference in men alone. We are uncertain whether doxycycline compared to ofloxacin reduces microbiological failure in men or women alone, or men and women together, nor if it reduces clinical failure or adverse events in men or women.Based on the fact that women suffer mainly asymptomatic infections, and in order to test the effectiveness and safety of the current recommendations (azithromycin, doxycycline and ofloxacin), for CT infection, especially in low and middle income countries, future RCTs should be designed and conducted to include a large enough sample size of women, and with low risk of bias. It is also important that future RCTs include adherence, CT resistance to antibiotic regimens, and risk of reinfection as outcomes to be measured. In addition, it is important to conduct a network meta-analysis in order to evaluate all those studies that included in one arm only the current antibiotic treatments for CT infection that are recommended by the updated clinical practice guidelines.

Paffoni, A., et al. (2024). "Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis A Systematic Review and Meta-Analysis." JAMA Network Open 7(1): E2354249.
	IMPORTANCE Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue. OBJECTIVE To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation.DATA SOURCES In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. STUDY SELECTION Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes. DATA EXTRACTION AND SYNTHESIS Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted. MAIN OUTCOMES AND MEASURES The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI. RESULTS This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97). CONCLUSIONS AND RELEVANCE This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.Copyright © 2024 American Medical Association. All rights reserved.

Paffoni, A., et al. (2021). "Folate Levels and Pregnancy Rate in Women Undergoing Assisted Reproductive Techniques: a Systematic Review and Meta-analysis." Reproductive sciences (Thousand Oaks, Calif.).
	Maternal nutrition is believed to be closely related to reproductive success and the importance of folate in the reproductive process and its involvement in fundamental biological systems are well known. The present systematic review and meta-analysis will focus on two main aspects: level of folate in women undergoing infertility treatments and association between folate status and success rate in assisted reproductive techniques. Although the importance of folate in the preconceptional phase is known, available data regarding the levels of folate in women who undergo infertility treatments are scarce. Referring to the threshold values generally used for the general population or for supplement users, the concentration of folate in the serum and erythrocytes of infertile women is adequate in the majority of the population with differences related to the geographic origin of the study populations. However, using the red blood cells folate threshold specifically indicated to prevent neural tube defects, the majority of available studies do not offer sufficient data to conclude on the real folate situation. As for the probability of success of ART treatments based on folate levels, our review did not reveal a significant effect.

Paffoni, A., et al. (2021). "Should rescue ICSI be re-evaluated considering the deferred transfer of cryopreserved embryos in in-vitro fertilization cycles? A systematic review and meta-analysis." Reproductive biology and endocrinology : RB&E 19(1): 121.
	Background: Total fertilization failure represents a particularly frustrating condition for couples undergoing in vitro fertilization. With the aim of reducing the occurrence of total fertilization failure, intracytoplasmic sperm injection (ICSI) has become the first choice over conventional in vitro fertilization (IVF) procedures although evidence of improved results is still debated and its use in couples without male factor infertility is not recommended. Among the strategies potentially useful to promote the use of conventional IVF, we herein call attention to the late rescue ICSI, which consists in performing ICSI after 18-24 h from conventional insemination on oocytes that show no signs of fertilization. This treatment has however been reported to be associated with a low success rate until recent observations that embryos derived from late rescue ICSI may be transferred after cryopreservation in a frozen-thawed cycle with improved results. The aim of the present study was to assess whether frozen embryos deriving from rescue ICSI performed about 24 h after conventional IVF may represent a valuable option for couples experiencing fertilization failure.; Methods: A systematic review on the efficacy of late rescue ICSI was performed consulting PUBMED and EMBASE.; Results: Including twenty-two original studies, we showed that clinical pregnancy rate per embryo transfer and implantation rate obtainable with fresh embryo transfers after rescue ICSI are not satisfactory being equal to 10 and 5%, respectively. The transfer of cryopreserved rescue ICSI embryos seems to offer a substantial improvement of success rates, with pregnancy rate per embryo transfer and implantation rate equal to 36 and 18%, respectively. Coupling rescue ICSI with frozen embryo transfer may ameliorate the clinical pregnancy rate for embryo transfer with an Odds Ratio = 4.7 (95% CI:2.6-8.6).; Conclusion: Results of the present review support the idea that r-ICSI coupled with frozen embryo transfer may overcome most of the technical and biological issues associated with fresh transfer after late r-ICSI, thus possibly representing an efficient procedure for couples experiencing fertilization failure following conventional IVF cycles.; Trial Registration: Prospero registration ID: CRD42021239026 . (© 2021. The Author(s).)

Pagan Megan, E., et al. (2022). "Are the Diagnosis and Treatment of Acute Cystitis in the Premenopausal, Pregnant, and Postmenopausal Women the Same? A Review of the Literature." Obstetrical & gynecological survey 77(3): 174-187.
	Importance: Acute cystitis is a common condition diagnosed in women. The diagnosis and treatment of this condition change throughout a woman's life. Understanding the differences in diagnosis and treatment in premenopausal, pregnant, and postmenopausal woman increases the likelihood of treatment success and decreases risk of complications from untreated or suboptimally treated infections.; Objective: The aim of this review is to describe the incidence, risk factor, pathophysiology, diagnosis, and management of acute cystitis and the similarities and differences of these aspects of the condition in the premenopausal, pregnant, and postmenopausal woman.; Evidence Acquisition: A PubMed, Web of Science, and CINAHL search was undertaken with the years 1990 to 2020 searched.; Results: There were 393 articles identified, with 103 being the basis of review. Multiple risk factors for acute cystitis have been identified and are largely consistent throughout a woman's lifetime with few exceptions. The diagnoses by group with common diagnostic tools, such as urinalysis, vary in specificity and sensitivity between these groups. Management also varies between groups, with pregnancy having specific limitations related to drug safety in regard to possible fetal effects posed by certain medications commonly used to treat acute cystitis.; Conclusions: Acute cystitis not only varies in presentation throughout a woman's lifespan, but also in appropriate diagnosis and treatment. Treatment of acute cystitis does have some commonalities between the groups; however, there are contraindications unique to each group. These differences are paramount to not only ensuring appropriate treatment but also treatment success.; Relevance: Acute cystitis is a common condition with different diagnostic and management recommendations throughout a woman's lifespan.

Pagano Ana, P., et al. (2022). "Energy Metabolism in Gynecological Cancers: A Scoping Review." International Journal of Environmental Research and Public Health 19(11).
	Determining energy requirements is vital for optimizing nutrition interventions in pro-catabolic conditions such as cancer. Gynecological cancer encompasses the most common malignancies in women, yet there is a paucity of research on its metabolic implications. The aim of this review was to explore the literature related to energy metabolism in gynecological cancers. We were particularly interested in exploring the prevalence of energy metabolism abnormalities, methodological approaches used to assess energy metabolism, and clinical implications of inaccurately estimating energy needs. A search strategy was conducted from inception to 27 July 2021. Studies investigating energy metabolism using accurate techniques in adults with any stage of gynecological cancer and the type of treatment were considered. Of the 874 articles screened for eligibility, five studies were included. The definition of energy metabolism abnormalities varied among studies. Considering this limitation, four of the five studies reported hypermetabolism. One of these studies found that hypermetabolism was more prevalent in ovarian compared to cervical cancer. Of the included studies, one reported normometabolism at the group level; individual-level values were not reported. One of the studies reported hypermetabolism pre- and post-treatment, but normometabolism when re-assessed two years post-treatment. No studies explored clinical implications of inaccurately estimating energy needs. Overall, commonly used equations may not accurately predict energy expenditure in gynecological cancers, which can profoundly impact nutritional assessment and intervention.

Page, A., et al. (2022). "Less Long Term (13 years) Graft Related Complications and Reinterventions with Light Rather than Heavy Weight Mesh Laparoscopic Sacrocolpopexy." International Urogynecology Journal 33(Supplement 2): S246-S247.
	Introduction: Prior to February 2007, patients undergoing laparoscopic sacrocolpopexy (LSCP) in our unit were implanted with a polypropylene (PP)-mesh (Gynemesh Prolene, Johnson&Johnson; Amid-I heavy weight ("HW" >=70 g/m2)1,2. Based on experimental findings that lighter implants do not induce bridging fibrosis3 and changes in marketed products, we moved to lighter weight poliglecaprone(PG)-PP hybrid mesh, which weigh 28g/m2 ("LW") after resorption of PG (ArtisynTM/UltraproTM, Johnson&Johnson). These experimental findings bear only clinical relevance if they translate into improved outcomes. Objective(s): To report on the occurrence, nature of, and reinterventions for graft related complications (GRC) and patient reported long term outcomes following LSCP with LW as opposed to HW-PP mesh. Method(s): Patients undergoing LSCP for symptomatic stage >=2 cervical/ vault prolapse are part of an ongoing prospective cohort study. Women are typically followed up yearly using a standardized subjective and objective assessment by an independent assessor. Patients not attending yearly visits are invited at regular audits, the last one in January 2021. As a consequence the maximum follow up for the first LW-implanted patient was 163 months. Herein we compare outcomes of two non-parallel cohorts (HW-mesh and LW-mesh implanted women) at similar duration of follow-up, including reinterventions (1) for GRC or (2) recurrent apical prolapse in all patients operated, and in assessed patients, (3) the Patient Global Impression of Changescore >=4 (PGIC), (4) the occurrence and (5) nature of GRC and (6) anatomical failure (C=-1 cm or greater). Data are reported as mean (SD), median (IQR), number (%), as appropriate. Student t-test, Chi square Fisher exact and survival analysis were used to compare groups. Result(s): We report on 101 HW and 238 LW-implanted women. There were no differences in baseline characteristics neither in follow-up period (97.0 months (IQR:16.0) and 92.5 months (IQR:58.0) respectively). The reoperation rate for GRC was lower in the LW-group (2.1%;5/238) than in the HW-group (18.8%;19/101;p=0.0002;HR=4.6 (95%-CI: 1.9-11.2), whereas for recurrent prolapse there was no difference (p=0.6). Reoperations for recurrent vault prolapse were scarce (0.0% in HW compared to 0.4% in LW). Of patients attending follow-ups the vast majority felt better (PGIC>=4) without difference between groups (HW:84.5%; LW:86.5%). GRC were more likely in HW-patients (22.8%;23/101) compared to LW-patients (7.3%;13/178; p=0.0002;HR=3.3; 95%-CI:1.6-7.1). GRC were symptomatic in 2.8% (5/178) of LW and in 16.8% (17/101) of HW-implanted women. There was no significant difference in anatomical failure at point C (1.7% (HW) and 6.1% (LW); p=0.13). Conclusion(s): The number of asymptomatic and symptomatic GRCs and reinterventions for GRC in patients operated with LW-mesh is significantly lower than with HW-mesh. There were no differences in long term subjective and objective outcomes neither reoperation rates for prolapse.

Page, A. S., et al. (2023). "Long-term Data on Graft-Related Complications After Sacrocolpopexy With Lightweight Compared With Heavier-Weight Mesh." Obstetrics and Gynecology 141(1): 189-198.
	OBJECTIVE: To estimate the long-term incidence and characteristics of graft-related complications, rate of reintervention for graft-related complications and prolapse, and subjective and anatomical outcomes after laparoscopic sacrocolpopexy with heavier-weight (more than 44 g/m2) compared with lightweight (28 g/m2) polypropylene mesh, the latter with resorbable poliglecaprone component. METHOD(S): We conducted a single-center study that compared two consecutive prospective cohorts of patients who were undergoing laparoscopic sacrocolpopexy for symptomatic stage 2 or greater cervical or vault prolapse, by using either heavier-weight polypropylene mesh or lightweight polypropylene mesh at a similar duration of follow-up. The primary outcome was the occurrence of graft-related complications and their nature. Secondary outcomes included reinterventions for graft-related complications, recurrent apical prolapse, a subjective outcome (PGIC [Patient Global Impression of Change] score 4 or higher), and an anatomical outcome (point C -1 cm or greater). RESULT(S): We identified consecutive patients: 101 were implanted with heavier-weight polypropylene, and 238 were implanted with lightweight polypropylene; all were audited at comparable follow-up times (heavier-weight mesh: 97 months [interquartile range 16 months]; lightweight mesh: 92.5 months [interquartile range 58 months]). Graft-related complications were more frequent in patients with heavier-weight than lightweight mesh (22.8% [23/101] vs 7.3% [13/178]; hazard ratio [HR] 3.3, 95% CI 1.6-7.1), more frequently symptomatic (heavier-weight mesh: 16.8% [17/101] vs lightweight mesh: 2.8% [5/178]; HR 6.0, 95% CI 2.5-14.3), and more frequently lead to reintervention for graft-related complications (heavier-weight mesh: 18.8% [19/101] vs lightweight mesh: 2.1% [5/238]; HR 4.6, 95% CI 1.9-11.2). The vast majority of patients improved (PGIC score 4 or higher), without difference between groups (heavier-weight mesh: 71/84 [84.9%]; lightweight mesh: 154/178 [86.5%]; HR 0.8, 95% CI 0.6-1.1); neither was there a difference in anatomical failure rate (heavier-weight mesh: 1/60 [1.7%] vs lightweight mesh: 8/131 [6.1%]; HR 0.3, 95% CI 0.1-1.4). Reoperations for recurrent vault prolapse were scarce (0.0% in heavier-weight mesh, vs 0.4% in lightweight mesh). CONCLUSION(S):In two consecutive cohorts, the number of graft-related complications, symptomatic graft-related complications, and reinterventions for graft-related complications were higher in patients implanted with heavier-weight polypropylene than when lightweight polypropylene was used. There were no differences in subjective, objective outcomes, and reoperation rates for prolapse.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04378400.FUNDING:To assist in this audit, the University Hospitals Leuven received support from Ethicon Endosurgery.Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

Pagni Roberta, L., et al. (2022). "Interleukin-6 and indoleamine-2,3-dioxygenase as potential adjuvant targets for Papillomavirus-related tumors immunotherapy." Frontiers in Immunology 13: 1005937.
	High-risk Human papillomavirus (HPV) infections represent an important public health issue. Nearly all cervical malignancies are associated with HPV, and a range of other female and male cancers, such as anogenital and oropharyngeal. Aiming to treat HPV-related tumors, our group developed vaccines based on the genetic fusion of the HSV-1 glycoprotein D (gD) with the HPV-16 E7 oncoprotein (gDE7 vaccines). Despite the promising antitumor results reached by gDE7 vaccines in mice, combined therapies may increase the therapeutic effects by improving antitumor responses and halting immune suppressive mechanisms elicited by tumor cells. Considering cancer immunosuppressive mechanisms, indoleamine-2,3-dioxygenase (IDO) enzyme and interleukin-6 (IL-6) stand out in HPV-related tumors. Since IL-6 sustained the constitutive IDO expression, here we evaluated the therapeutic outcomes achieved by the combination of active immunotherapy based on a gDE7 protein-based vaccine with adjuvant treatments involving blocking IDO, either by use of IDO inhibitors or IL-6 knockout mice. C57BL/6 wild-type (WT) and transgenic IL-6 -/- mice were engrafted with HPV16-E6/E7-expressing TC-1 cells and treated with 1-methyl-tryptophan isoforms (D-1MT and DL-1MT), capable to inhibit IDO. In vitro , the 1MT isoforms reduced IL-6 gene expression and IL-6 secretion in TC-1 cells. In vivo , the multi-targeted treatment improved the antitumor efficacy of the gDE7-based protein vaccine. Although the gDE7 immunization achieves partial tumor mass control in combination with D-1MT or DL-1MT in WT mice or when administered in IL-6 -/- mice, the combination of gDE7 and 1MT in IL-6 -/- mice further enhanced the antitumor effects, reaching total tumor rejection. The outcome of the combined therapy was associated with an increased frequency of activated dendritic cells and decreased frequencies of intratumoral polymorphonuclear myeloid-derived suppressor cells and T regulatory cells. In conclusion, the present study demonstrated that IL-6 and IDO negatively contribute to the activation of immune cells, particularly dendritic cells, reducing gDE7 vaccine-induced protective immune responses and, therefore, opening perspectives for the use of combined strategies based on inhibition of IL-6 and IDO as immunometabolic adjuvants for immunotherapies against HPV-related tumors.; Competing Interests: BP and LA hold ownership interest, including patents, in ImunoTera Soluções Terapêuticas Ltda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Pagni, Souza, Pegoraro, Porchia, da Silva, Aps, Silva, Rodrigues, Sales, Ferreira and Moreno.)

Pain, F.-A., et al. (2023). "Patterns of recurrence in surgically treated women for TP53-mutated endometrial carcinomas." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49(9): 106954.
	Objective: To describe the patterns of recurrence and the prognosis of patients with a recurrent TP53 mutated endometrial carcinoma treated initially by surgery.; Methods: All patients with endometrial carcinoma, treated at hospital European Georges Pompidou between 2001 and 2021 were retrospectively included. Patients were separated into two groups: TP53-mutated and not TP53-mutated (POLE/ultramutated-like (POLEmut), dMMR (mismatch repair-deficient) and NSMP (No specific molecular profile)). We estimated survival using recurrence free survival, overall survival and overall survival from recurrence. The risk of recurrence according to TP53 status and the type of recurrence (locoregional recurrence, peritoneal recurrence, and metastasis) were also compared between the two groups.; Results: Two hundred and ninety-one patients with endometrial carcinoma were included. Of these, 57 were TP53-mutated and 234 patients were not TP53-mutated. TP53 mutated patients had the worst recurrence free survival and overall survival (p < 0.001 for each). The hazard rate of recurrence was higher during the first three years for TP53 mutated endometrial carcinoma then tend to join the one of no TP53 mutated. There was a statistical difference between the two groups in terms of cumulative incidence of peritoneal recurrence (p = 0.002). There was, however, no statistical difference in overall survival from recurrence.; Conclusions: TP53-mutated endometrial carcinoma were more likely to experience a recurrence during the first three years and most often peritoneal recurrence compared to not TP53-mutated. TP53 status in endometrial carcinoma could be useful to define follow-up. Further prospective studies are required to assess the predictive impact of TP53 mutation on chemotherapy benefit.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Painter, C. E., et al. (2021). "Mesh Complication Rates Following Pelvic Radiation Therapy in Women With History of Synthetic Midurethral Sling Implantation." Female Pelvic Medicine & Reconstructive Surgery 27(2): e476-e480.
	OBJECTIVE: To estimate the risk of mesh complications in women with and without subsequent pelvic and abdominal radiation therapy (RT). METHODS: We identified women within a large health care organization who underwent mesh-augmented surgery for pelvic floor disorders between 2008 and 2014 and subsequently received RT prior to 2018. We compared them to a randomly selected group of women who underwent similar mesh-augmented pelvic reconstructive surgery without RT in a 1:4 ratio. Mesh complications were identified through chart review corroborated with the ninth and tenth revisions of the International Classification of Diseases and Current Procedural Terminology codes for mesh complications. Mesh complications between groups were compared using survival analysis and Cox proportional hazards models. RESULTS: We identified 36 women with RT and compared them with 144 women without RT. Indications for mesh implantation and concomitant vaginal procedures were similar between the groups. The majority of mesh implants (94.4%) were midurethral slings. Twelve mesh complications (6.7%) were identified, with similar rates in the RT (8.3%) and no-RT (6.2%) groups (P = 0.65). The risk of mesh complications did not differ between groups when compared using the Cox proportional hazards model, controlling for age, body mass index, diabetes, menopausal status, and smoking (hazard ratio, 1.19; 95% confidence interval, 0.802-1.787). CONCLUSIONS: There was no difference in the occurrence of mesh-related complications between women with and without RT. Abdominopelvic RT may not substantially increase the risk of mesh complications following placement of a synthetic sling for stress urinary incontinence. The need for future RT may only be a minor factor in counseling patients on the risks of mesh implants for pelvic floor disorders.

Paiva, J. M., et al. (2023). "The efficacy of internet-delivered cognitive-behavioral therapy for posttraumatic stress disorder according to the mean age of patients: a systematic review and meta-analysis." Psychology, health & medicine: 1-15.
	Internet-delivered cognitive-behavioral therapy (I-CBT) is effective in treating post-traumatic stress disorder (PTSD) symptoms, offering enhanced accessibility and cost-effectiveness. However, it's important to note that these technologies may not be suitable for all age groups. Therefore, we conducted a systematic review and meta-analysis to determine if the effectiveness of I-CBT in treating PTSD varies based on the patients' mean age. We conducted a systematic review of the literature, focusing on randomized controlled trials (RCTs) in the ISI Web of Science, PubMed/MEDLINE, and PsycINFO databases. Following this, we performed a meta-analysis and evaluated the risk of bias using the Cochrane risk of bias quality assessment tool. In this study, we examined patient-related factors (civil or military status, age, and gender), clinical characteristics (baseline PTSD severity and type of trauma), and treatment characteristics (type of intervention, synchronous or asynchronous delivery, and the number of sessions) as independent variables. The dependent variable was the reduction in mean PTSD symptoms. Five RCTs out of 1,552 screened studies were included in this review, all of which showed some level of concern regarding potential bias. Our meta-analysis indicates that I-CBT is equally effective regardless of patients' mean age. Since all RCTs included only provide the mean age of the patients, further randomized controlled trials should address the effectiveness of I-CBT among different age groups.

Paiz Janini, C., et al. (2022). "Association between mistreatment of women during childbirth and symptoms suggestive of postpartum depression." BMC Pregnancy and Childbirth 22(1): 664.
	Background: Postpartum depression is a common condition in the pregnancy and postpartum cycle. The development of this condition is multifactorial and can be influenced by previous traumas. This study sought to verify whether there is an association between having been exposed to mistreatment during childbirth and presenting symptoms suggestive of postpartum depression.; Methods: This is a cross-sectional study, with the inclusion of 287 women without complications in childbirth, randomly selected from two maternity hospitals of Porto Alegre, southern Brazil, in 2016. Four weeks after delivery, the postpartum women answered a face-to-face interview about socioeconomic aspects, obstetric history, health history, and childbirth experience (practices and interventions applied) and completed the Edinburgh Postnatal Depression Scale (EPDS). From the perception of women regarding the practices performed in the context of childbirth care, a composite variable was created, using item response theory, to measure the level of mistreatment during childbirth. The items that made up this variable were: absence of a companion during delivery, feeling insecure and not welcome, lack of privacy, lack of skin-to-skin contact after delivery, not having understood the information shared with them, and not having felt comfortable to ask questions and make decisions about their care. To define symptoms suggestive of postpartum depression, reflecting on increased probability of this condition, the EPDS score was set at ≥ 8. Poisson Regression with robust variance estimation was used for modeling.; Results: Women who experienced mistreatment during childbirth had a higher prevalence of symptoms suggestive of postpartum depression (PR 1.55 95% CI 1.07-2.25), as well as those with a history of mental health problems (PR 1.69 95% CI 1.16-2.47), while higher socioeconomic status (A and B) had an inverse association (PR 0.53 95% CI 0.33-0.83).; Conclusions: Symptoms suggestive of postpartum depression seem to be more prevalent in women who have suffered mistreatment during childbirth, of low socioeconomic status, and with a history of mental health problems. Thus, qualifying care for women during pregnancy, childbirth and postpartum and reducing social inequalities are challenges to be faced in order to eliminate mistreatment during childbirth and reduce the occurrence of postpartum depression. (© 2022. The Author(s).)

Pak, K. and H. J. Yoon (2023). "Impact of 18F-FDG PET on the Management in Patients With Recurrent Gynecologic cancer: A Meta-analysis." Clinical nuclear medicine.
	PURPOSE: Gynecological cancer is the most prevalent cancer among women worldwide. We performed a meta-analysis to assess the impact of 18F-FDG PET on the management of patients with recurrent gynecological cancers, including cervical, uterine, and ovarian cancers. METHODS: We systematically searched MEDLINE and EMBASE databases for English-language publications. All published studies on the impact of PET scans on the management of patients with recurrent gynecological cancers were reviewed. The proportion of management change (%), defined as the percentage of patients whose management changed after FDG PET to those who underwent FDG PET, was calculated. The data from each study were analyzed using MedCalc Statistical Software version 14.12.0 (MedCalc Software, Ostend, Belgium). RESULTS: Nineteen studies including 6191 patients were eligible for inclusion. The impact of FDG PET scan for detecting recurrence/metastasis in patients with gynecologic cancer was evaluated using management change rates, ranging from 9.4% to 60.7% with a pooled effect of 42.0% (95% confidence interval [CI], 34.5%-49.6%; I2 = 92.9%). In the subtype analysis, FDG PET scanning resulted in changes in the management in 48.5% (95% CI, 37.8%-59.3%; I2 = 67.8%) of cervical cancer, 34.7% (95% CI, 33.4%-36.0%; I2 = 0%) of uterine cancer, and 40.3% (95% CI, 26.7%-54.7%; I2 = 95.2%) of ovarian cancer cases. CONCLUSIONS: FDG PET has a significant impact on the restaging of patients with gynecological cancer. These findings suggest that FDG PET should be performed, especially in cases of suspected recurrence/metastasis in the main gynecologic cancer types, including cervical, ovarian, and uterine cancers.

Pak, S. and Y. J. Choi (2023). "The precision chemotherapy to improve the epithelial ovarian cancer prognosis." Cancer Research 83(7 Supplement).
	Purpose: Recurrence is common in ovarian cancer patients, even in those patients who show complete response after first-line chemotherapy, 80% of the patients experience a recurrence. So gynecologic oncologists often have to consider several factors when choosing next chemotherapy regimen. Therefore, this study aimed to find serial chemotherapy regimen choice to anticipate patients' better prognosis. Material(s) and Method(s): We reviewed 656 patients diagnosed ovary cancer in one tertiary institutional hospital between 2006 and 2020. Patents' clinic-pathologic characteristics, primary treatment, chemotherapy regimens, survival outcomes were collected. We divided patients into several groups according to their chemotherapy regimen by mechanism of action and compared them. 1st line chemotherapy(CTx) type 1: carboplatin-paclitaxel, carboplatin-docetaxol, cisplatinpaclitaxel, cisplatin-docetaxol2nd line CTx type 1: carboplatin-paclitaxel, carboplatin-docetaxol, cisplatin-paclitaxel, cisplatin-docetaxol2nd line CTx type 4: carboplatin-gemcitabine2nd maintenance CTx type 2: PARP inhibitor(PARPi)2nd line CTx Type 5: Platinum + topoisomerase inhibitor 2nd line CTx Type 6(cisplatin-vinorelbine)2nd line CTx Type 8(topoisomerase inhibitor only) 2nd line CTx Type12 (single taxol) The survival rate of ovary cancer patients decreased from stage 1 to stage 4.Among 1st line CTx type 1 and 2nd line CTx type(1 or 4) patients, those who used PARPi in 2nd line maintenance CTx(n=14) had a higher death rate than those who did not receive maintenance CTx or received that other than PARPi(hazard ratio 1.44). In the 1st line CTx 1~4 group, we divided patients according to 2nd line CTx type. We compare 2nd line CTx type 5 group(n=30) with type 6+8+12 group(n=26). The death rate was of type 5 group was higher than type 6+8+12 group. And Overall survival of 2nd line CTx type 5 group was 22 months, that of 2nd line CTx type 6+8+12 group was 26 months. Conclusion(s): When changing the chemotherapy regimen in the recurrence of ovarian cancer, the survival rate or overall survival may vary depending on the order in which the regimen is used. If we collect patients data more broadly, the predictive power will be better.

Pakai, A., et al. (2022). "PCR42 Examination of Quality of Life and Sexual Functions Among Women With Cervical Cancer." Value in Health 25(12 Supplement): S398.
	Objectives: The aim of our research is to assess the sexual function of women with cervical cancer after surgery or chemotherapy and radiation, and to observe the effects of cervical cancer on quality of life and treatment-related symptoms. Method(s): Our quantitative cross-sectional survey was conducted between May and December 2021. The target group of non-random, convenience sampling is I.-III. women with stage cervical cancer who underwent surgery, radiation and / or chemotherapy, and have a regular active sex life (n=115). Those who relapsed, metastasized, and refused participation were excluded from our survey. Our data collection method was an anonymous questionnaire consisting of self-edited questions and validated questionnaires. A validated questionnaire (EORTC QLQ-CX24) was used to assess the quality of life of patients with cervical cancer. Another, FSFI questionnaire was used, which shows sexual functions of women. Statistical experiments were performed using SPSS 25.0 and Excel Microsoft Office 365 software, descriptive statistics and two-sample t-test, Chi-square test, ANOVA, and Pearson correlation were used to analyse the data (p<0.05). Result(s): 36.5% of the women interviewed in our study received radiotherapy, 33.9% received chemotherapy, and 93% underwent surgery. Most of them, 60% of the participants have sexual dysfunction. There was no significant difference in the total sexual function score of women in stage I and II-III (p=0.362). The mean score of the total sexual function (mean=16.56+/-9,445) of those receiving radiotherapy was significantly lower than the mean score of those who did not receive radiotherapy (mean=24.55+/-10,449) (p=0.001). Among the participants who experienced urinary retention problem after the treatments (72.7%), there was a significantly higher rate of sexual dysfunction (p=0.008). Conclusion(s): Women with cervical cancer in our research have significant sexual dysfunction. Side effects after treatments also significantly impair the quality of life and sexual function.Copyright © 2022

Paknahad, Z., et al. (2021). "The role of micronutrients in male and female fertility: A review study." Iranian Journal of Obstetrics, Gynecology and Infertility 24(1): 87-98.
	Introduction: Fertility means the ability to have a child that is one of the causes of family formation. Several factors can affect fertility. Micronutrients are essential for the body's anabolic and catabolic activities, so they may be effective factors on fertility. Therefore, this study was conducted with aim to determine the role of micronutrients in male and female fertility. Method(s): In this review study, the Persian databases of Magiran, SID and the English databases of Pubmed, Scopus, SID, Elsevier, Web Of Sciences and the Google Scholar search engine were searched using the English keywords of Infertility, fertility Infertility, Fertility, Male Infertility, Semen, Semen Parameters, Systematic Review, Clinical Trial, Case-Control, Female Infertility, Micronutrients, Vitamin A, Vitamin B, Vitamin C, Ascorbic Acid, Vitamin D, Vitamin E, Antioxidants, Folic Acid, Zinc and their Persian equivalents in the period of 1990-2020. Numerous quantitative and qualitative studies that were similar to the present study in terms of content were selected and evaluated. Result(s): Among 1052 articles, 22 studies which were more related to the aim of the present study were selected and evaluated. The results of reviewing the studies showed that the consumption of micronutrients including vitamins D, E, C, A, zinc, iodine, selenium, folate and omega-3 fatty acids can play a role in improving male and female fertility parameters. Deficiency of each of them has been seen in infertile men and women. Conclusion(s): Since nutrition has moved towards ready meals and lifestyle has moved towards a sedentary life and as a result, the body does not meet the essential needs for basic activities, it seems that the recommendation to consume micronutrients in men and women can prevent many fertility problems and reduce the cost of infertility treatment.Copyright © 2021, Mashhad University of Medical Sciences. All rights reserved.

Pakravan, F. and Z. Poschinski (2023). "MODIFIED POPS SURGERY SHOWS GOOD RESULTS IN SHORT TIME FOLLOW UP IN PATIENTS WITH RECTAL PROLAPSE." Diseases of the Colon and Rectum 66(6): e547-e548.
	Purpose/Background: Rectal prolapse is mostly common in patients over 50 years old, especially in women with simultaneous pelvic floor conditions. There are several abdominal and perineal surgical approaches including POPS (pelvic organs prolapse suspension) by Longo. In this modified version, the mesh is not fixated at the vagina but ventral of the rectum in order to elevate the rectum and eradicate the rectal prolapse. Methods/Interventions: Between October 2016 and October 2021, 54 patients (11 male, 43 female, age 68 (43-87) years, median follow up 13.8 months) underwent modified POPS operation. Most patients underwent previous surgeries, including hysterectomy, STARR surgery and perineal prolapse resection. Results/Outcome(s): The surgery was successful in all patients: there were no cases of postoperative bleeding or infection. 26 patients (48.1%) were symptom free after surgery, 20 patients (37%) had distinct improvement. 8 patients (14.8%) only experienced a minor improvement. During follow-up, 42 patients (77.7%) reported a sustainable improvement of symptoms. Conclusions/Discussion: The ventral rectopexy with modified POPS surgery seems to be safe and successful in this patient cohort. It might be a more protecting surgical method compared to other methods used at the moment. There is a need for longer follow-up times and larger patient cohorts in order to prove these results.

Paksoy, N., et al. (2022). "Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study." Medicine 101(45): e31726.
	Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pal, A., et al. (2022). "Apoptotic and autophagic death union by Thuja occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle." Journal of integrative medicine 20(5): 463-472.
	Objective: "Multi-targeting" drugs can prove fruitful to combat drug-resistance of multifactorial disease-cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts.; Methods: Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MtMP) by rhodamine 123 (Rh123) staining. Apoptosis and autophagy inductions were studied by acridine orange/ethidium bromide (AO/EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency.; Results: Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC 50 ) of 17.3 µL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MtMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways-apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT, showed greater anti-proliferative and anti-migratory potential at an IC 50 of 77 µg/mL, along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk.; Conclusion: Robust "multi-targeting" anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertained its therapeutic efficacy for HPV infections.; Competing Interests: Declaration of competing interest Authors declare that they have no conflicts of interest. (Copyright © 2022 Journal of Integrative Medicine Editorial Office. Published by Elsevier B.V. All rights reserved.)

Pal, A., et al. (2022). "Evaluation of the effectiveness of yoga in management of premenstrual syndrome: a systematic review and meta-analysis." Journal of Psychosomatic Obstetrics and Gynaecology 43(4): 517-525.
	Aim: The management of Premenstrual Syndrome (PMS) is still evolving due to the modest effect sizes of the available treatment modalities. Yoga as therapeutic intervention in PMS has been gathering interest amongst researchers. The current manuscript reviews the evidence surrounding yoga in PMS. Methods: This manuscript was a systematic review and meta-analysis evaluating the effectiveness of yoga on the total scores and sub-domains of PMS after studies were identified using a pre-defined selection criterion after a search in PubMed, Google Scholar, Scopus and Web of Science. Both quantitative and qualitative analysis of the accumulated data was performed. Overall, 14 studies were identified for the review, 11 of which were used for the purpose of quantitative analysis. Results: The studies were heterogenous in terms of the design, yoga regimes, nature of interventions and tools used for outcome measures. It was found that yoga was beneficial in the management of PMS. This benefit was also seen when all the sub-domains of PMS were individually examined except physical sub-domain. Conclusion: Though there were certain limitations in our review like heterogeneity in studies, possibility of publication bias and restrictive selection criterion; it supported that yoga can be beneficial in patients with PMS.

Palacios, S. (2023). "Sequential treatment in vulvovaginal atrophy." Climacteric : the journal of the International Menopause Society 26(4): 292-295.
	Vulvovaginal atrophy (VVA) is a chronic and progressive disease that affects sexuality and quality of life. VVA is preventable and treatable, but requires long-term and often sequential treatment. Sequential treatment consists of designing a strategy that uses one or more medications for a long enough time to achieve the desired benefits with minimal risk and maximum adherence. Currently available therapeutic options consist of topical over-the-counter products (including non-hormonal lubricants and moisturizers applied to the vagina), systemic hormone therapy and estrogens, and prescribed vaginal dehydroepiandrosterone (DHEA). In addition, we have a selective estrogen receptor modulator, ospemifene, and new energy-based treatments (laser and radiofrequency). There are clear differences between the treatments both in the mechanism of action and in the efficacy. Compliance is very low, and patients complain about the use of the vaginal route, often due to its low efficacy, or express fear of the long-term use of estrogens or the price of the treatments. We believe that, as a first option, and for physiological, preventive and efficacy reasons, we should consider the prescription of treatments that work on estrogen receptors. As a second option, there are vaginal moisturizers, which are effective on symptoms but do not prevent or improve conditions. Finally, techniques using heat, which although each time represent a clearer alternative, but on the other hand are the cost and the long-term safety data, give us a third option. Of course, we consider that vulvar moisturizers and lubricants can be used at any time.

Palacios, S., et al. (2023). "Expert opinion on the treatment of vulvovaginal atrophy with ospemifene based on new evidence." Climacteric : the journal of the International Menopause Society 26(4): 388-391.
	Vulvovaginal atrophy (VVA) is an underdiagnosed and undertreated chronic condition resulting in physiological and histological changes in the genitourinary tract of postmenopausal women. Treatment of moderate to severe VVA includes local estrogens, dehydroepiandrosterone (DHEA) and oral ospemifene, a third-generation selective estrogen receptor modulator (SERM). Due to venous thromboembolism (VTE) safety concerns classically associated with the SERM class, and as part of its original marketing authorization approval (MAA), the European Medicines Agency (EMA) requested the performance of a 5-year post-authorization safety study (PASS) to study the incidence rate of VTE among women receiving ospemifene. The results have led to important regulatory changes to ospemifene's labeling, extending its indication and eliminating concerted risk management measures. A panel of experts discussed and reached consensus on the impact of these regulatory changes on clinical practice, reflecting on the reassurance of ospemifene's benefit-risk balance and recommending its positioning as a first-line pharmacological treatment option for moderate to severe VVA together with local therapies. In a scenario where different treatments present similar efficacy and safety profiles, a shared decision between clinician and patient, according to her needs and preferences over time, is fundamental to improve adherence and persistence with sequential treatment, contributing to the achievement of health outcomes.

Palacios, S., et al. (2021). "Efficacy of low-dose vaginal 17b-estradiol versus vaginal promestriene for vulvovaginal atrophy." Climacteric.
	Objective: vulvovaginal atrophy is frequent, can be bothersome and can impair quality of life in postmenopausal women. The main objective of this prospective, randomized study was to compare the acceptability of low‐dose vaginal 17b‐estradiol (estradiol) tablets and vaginal promestriene cream in postmenopausal women with moderate‐to‐severe symptomatic vulvovaginal atrophy. Methods: overall, 120 patients were randomized to receive estradiol or promestriene (n = 60 per group). Acceptability was assessed with a specific questionnaire. Symptom intensity, the Vaginal Health Index (VHI), vaginal pH and the Vaginal Maturation Index were also evaluated. Results: acceptability was higher for estradiol tablets. Compared to promestriene cream, hygiene and ease of use were greater after 4 weeks (p = 0.011 and p = 0.001, respectively) and after 12 weeks (p = 0.009 and p = 0.011, respectively). Reduction of symptom intensity was greater with estradiol. Both treatments improved the VHI and decreased vaginal pH. However, superficial cell percentages increased significantly (p < 0.001) with estradiol but not with promestriene (p = 0.241), with a statistically significant difference between means (p = 0.004). Conclusion: our results support the use of vaginal low‐dose estradiol tablets as compared to vaginal promestriene cream for the management of moderate‐to‐severe symptomatic vulvovaginal atrophy in postmenopausal women. ClinicalTrials.gov Identifier: NCT04232813

Palacios, S., et al. (2022). "Efficacy of low-dose vaginal 17β-estradiol versus vaginal promestriene for vulvovaginal atrophy." Climacteric : the journal of the International Menopause Society 25(4): 383-387.
	Objective: Vulvovaginal atrophy is frequent, can be bothersome and can impair quality of life in postmenopausal women. The main objective of this prospective, randomized study was to compare the acceptability of low-dose vaginal 17β-estradiol (estradiol) tablets and vaginal promestriene cream in postmenopausal women with moderate-to-severe symptomatic vulvovaginal atrophy.; Methods: Overall, 120 patients were randomized to receive estradiol or promestriene ( n = 60 per group). Acceptability was assessed with a specific questionnaire. Symptom intensity, the Vaginal Health Index (VHI), vaginal pH and the Vaginal Maturation Index were also evaluated.; Results: Acceptability was higher for estradiol tablets. Compared to promestriene cream, hygiene and ease of use were greater after 4 weeks ( p = 0.011 and p = 0.001, respectively) and after 12 weeks ( p = 0.009 and p = 0.011, respectively). Reduction of symptom intensity was greater with estradiol. Both treatments improved the VHI and decreased vaginal pH. However, superficial cell percentages increased significantly ( p < 0.001) with estradiol but not with promestriene ( p = 0.241), with a statistically significant difference between means ( p = 0.004).; Conclusion: Our results support the use of vaginal low-dose estradiol tablets as compared to vaginal promestriene cream for the management of moderate-to-severe symptomatic vulvovaginal atrophy in postmenopausal women.; Clinicaltrials.gov Identifier: NCT04232813.

Palafox-Gómez, C., et al. (2023). "Adding a ketogenic dietary intervention to IVF treatment in patients with polycystic ovary syndrome improves implantation and pregnancy." Reproductive toxicology (Elmsford, N.Y.) 119: 108420.
	Patients with polycystic ovary syndrome (PCOS) on a high-carbohydrate diet intrinsically suffer from exacerbated glucotoxicity, insulin resistance (IR), and infertility. Lowering the carbohydrate content has improved fertility in patients with IR and PCOS; however, the effects of a well-controlled ketogenic diet on IR and fertility in PCOS patients undergoing in vitro fertilization (IVF) have not been reported. Twelve PCOS patients with a previous failed IVF cycle and positive for IR (HOMA1-IR>1.96) were retrospectively evaluated. Patients followed a ketogenic diet (50 g of total carbohydrates/1800 calories/day). Ketosis was considered when urinary concentrations were > 40 mg/dL. Once ketosis was achieved, and IR diminished, patients underwent another IVF cycle. The nutritional intervention lasted for 14 ± 11 weeks. Carbohydrate consumption decreased from 208 ± 50.5 g/day to 41.71 ± 10.1 g/day, which resulted in significant weight loss (-7.9 ± 1.1 kg). Urine ketones appeared in most patients within 13.4 ± 8.1 days. In addition, there was a decrease in fasting glucose (-11.4 ± 3.5 mg/dl), triglycerides (-43.8 ± 11.6 mg/dl), fasting insulin (-11.6 ± 3.7 mIU/mL), and HOMA-IR (-3.28 ± 1.27). All patients underwent ovarian stimulation, and compared to the previous cycle, there was no difference in oocyte number, fertilization rate, and viable embryos produced. However, there was a significant improvement in the implantation (83.3 vs. 8.3 %), clinical pregnancy (66.7 vs. 0 %), and ongoing pregnancy/live birth rates (66.7 vs. 0 %). Here, restriction in carbohydrate consumption in PCOS patients induced ketosis, improved key metabolic parameters, and decreased IR. Even though this did not affect oocyte or embryo quality or quantity, the subsequent IVF cycle significantly improved embryo implantation and pregnancy rates.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Palaia, I., et al. (2022). "Preoperative low-residue diet in gynecological surgery." European Journal of Obstetrics, Gynecology, and Reproductive Biology 271: 172-176.
	Objective: To evaluate the impact of preoperative low-residue diet on intra- and postoperative outcomes among gynecological surgical patients.; Methods: This is a surgeon-blind, randomized controlled trial enrolling patients undergoing elective surgery for either benign disease or endometrial carcinoma. Patients were preoperatively randomized to receive either low-residue diet (arm A) or free diet (arm B) starting from three days before surgery. The primary outcome was the quality of the surgical field (scored using a 5-point scale, from poor to excellent). Secondary outcomes were postoperative pain (assessed through VAS scale), postoperative complications, operative time, time to first passage of flatus, length of hospital stay. Perioperative data were collected and compared between groups.; Results: A total of 96 patients were enrolled and randomized in arm A (n = 49; 51%) and arm B (n = 47; 49%). The mean age was 47.8 ± 15.6 years in arm A and 48.1 ± 11.3 years in arm B. Endometrial cancer patients were 16.3% in arm A and 10.6% in arm B, and patients with benign disease were 83.7% and 89.4%, respectively. The surgical evaluation of the small intestine was scored < 3 in 2.0% of arm A patients versus 31.9% in arm B (Odds Ratio (OR), 0.04 [95% CI, 0.01-0.35]; p < 0.001), and in 6.1% and 44.7% (OR, 0.08 [95% CI, 0.02-0.30]; p < 0.001), respectively, for large intestine. The mean operative time was 90.4 ± 33.4 min in arm A versus 111.6 ± 37.5 in arm B (Mean Difference (MD): -21.20 [95% CI, -35.43, -6.97]; p = 0.003). The number of patients who reported the time to first flatus within 24 h after surgery was significantly higher in arm A compared with arm B (77.6% vs 44.7%; OR, 4.28 [95% CI, 1.77-10.35]; p = 0.002). No significant differences in terms of postoperative complications, pain, and length of hospital stay were observed between the two groups.; Conclusion: Introducing a preoperative low-residue diet could improve the quality of the surgical field and reduce both the operative duration and the time to first passage of flatus among patients undergoing gynecological surgery. Further large-scale studies are required to confirm these findings. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Palaia, I., et al. (2022). "Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer." The Journal of Sexual Medicine 19(4): 613-619.
	Background: Cervical cancer survivors report the worst quality of life (QoL) among all cancer survivors and this is mainly due to their younger age and the long-term treatment sequelae.; Aim: The purpose of this study is to assess the long-term QoL and sexual function of locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH) instead of the standard chemoradiotherapy.; Methods: This is a retrospective case-control study including LACC patients (FIGO stage IIB-IVA) treated with the NACT-RH strategy and a control group of healthy women undergoing hysterectomy for uterine fibromatosis in the same period.; Outcomes: Main outcome measures were the EORTC QLQ-C30 and EORTC QLQ-CX24 for quality of life and Female Sexual Function Index (FSFI) for sexual function.; Results: Overall, 96 patients were included: 48 LACC and 48 controls. The mean age at diagnosis was 45.5 ± 9.0 and 47.0 ± 7.8, respectively (P = .38). Compared to controls, LACC patients reported lower mean scores for the global health status (69.4 ± 22.6 vs 81.2 ± 24.3; Mean Difference (MD): -11.80 [95% CI: -21.19, -2.41]; P = .016), QLQ-C30 functional scale (80.1 ± 22.6 vs 92.4 ± 14.9; MD: -12.30 [95% CI: -19.96, -4.64]; P = .002), QLQ-Cx24 functional scale (55.5 ± 25.0 vs 80.4 ± 22.4; MD: -24.00 [95% CI: -34.40, -15.40]; P < .001), and the total FSFI (19.3 ± 9.6 vs 26.2 ± 9.9; MD: -6.90 [95% CI: -10.80, -3.00]; P < .001). On the other hand, LACC patients reported higher mean scores on the QLQ-C30 (16.9 ± 22.1 vs 8.4 ± 16.6; MD: 8.50 [95% CI: 0.68, 16.32]; P = .03) and QLQ-CX24 (26.0 ± 28.8 vs 15.0 ± 11.7; MD: 11.00 [95% CI: -2.21, 19.79]; P = .01) symptoms scales.; Clinical Implications: The confirmed poor quality of life even in surgically treated LACC survivors underlines the importance of tailoring parametrectomy based on lymph node status and developing personalized strategies.; Strengths and Limitations: The study assessed the long-term QoL and sexual function in the specific subpopulation of LACC patients treated with NACT-RH. Main limitations include the small sample size and the retrospective design.; Conclusion: LACC long-term survivors treated with NACT-RH experience poor QoL and sexual dysfunction. Palaia I, Santangelo G, Caruso G, et al. Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer. J Sex Med 2022;19:613-619. (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Palaiologos, K., et al. (2023). "Ultra-radical surgery for advanced ovarian cancer: a retrospective cohort study in a tertiary referral cancer center in the UK." Minerva Obstetrics and Gynecology.
	BACKGROUND: Ovarian cancer is the leading cause of death from gynecological cancer in the UK. The standard of care is a combination of surgery and chemotherapy. The aim of the treatment is the resection of all macroscopic disease. In selected cases of advanced ovarian cancer this is achieved with ultra-radical surgery. However, NICE encourages further research due to low quality evidence on the safety and efficacy of this extensive surgery. The aim of this study was to examine the morbidity and survival rates of ultra-radical surgery for advanced ovarian cancer performed in our unit and compare our findings with the current literature. METHOD(S): This is a retrospective study of 39 patients diagnosed with stage IIIA-IV ovarian and primary peritoneal cancer who underwent surgery in our unit between 2012 and 2020. The main outcome measures were the perioperative complications, the disease-free survival, the overall survival rate and the recurrence rate. RESULT(S): The study enrolled 39 patients with stages IIIA-IV who were treated in our unit between 2012 and 2020. 21 patients were at stage III (53.8%) whereas 18 (46.1%) at stage IV. 14 patients underwent primary and 25 secondary debulking surgery. Major and minor complications occurred 17.9% and 56.4% of the patients, respectively. Complete cytoreduction following surgery was achieved in 24 cases (61.5%). The mean and the median survival time were 4.8 years and 5 years, respectively. The mean disease-free survival time was 2.9 years while median disease-free survival time was 2 years. Age (P=0.028) and complete cytoreduction (p=0.048) were found to be significantly associated with survival. Primary debulking surgery was significantly associated with lower probability of recurrence (P=0.049). CONCLUSION(S): Although the number of patients is relatively small, our study indicates that ultra-radical surgery in centers with high expertise may result in excellent survival rates with an acceptable rate of major complications. All patients in our cohort were operated by an accredited gynecological oncologist and a hepatobiliary general surgeon with a special interest in ovarian cancer. A few cases required input from a colorectal and a thoracic surgeon. We believe that the careful selection of the patients that can benefit from ultra-radical surgery and our model of joint surgery can explain our excellent results. Further research is essential to establish that ultra- radical surgery has an acceptable rate of morbidity for patients with advanced ovarian cancer.

Palani, D., et al. (2022). "A Dosimetric Analysis of Modified Volumetric Modulated Arc Therapy for Bone Marrow Sparing Radiotherapy in Cervical Cancer-An alternative Approach to Conventional VMAT." Asian Pacific journal of cancer prevention : APJCP 23(12): 4323-4332.
	BACKGROUND: External beam radiotherapy remains the primary treatment modality in cervical cancer. Nowadays Intensity Modulated Radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are increasingly being used to reduce normal tissue toxicity. The drawback of conventional VMAT is that a considerable volume of pelvic bone marrow receives a low dose. AIM: We analyzed whether there was a way to reduce the volume of the low dose regions of bone marrow, and assessed the potential benefit of conventional-4Arc (C-4Arc VMAT), and Modified-4Arc (M-4Arc VMAT) over the conventional 2 ARC VMAT. MATERIALS AND METHODS: Twelve clinically proven locally advanced cervical cancer patients treated with concurrent chemo-radiotherapy by Conventional VMAT (RapidArc) in dual rotation mode (C-2Arc VMAT) were selected for this study.C-4Arc VMAT and M-4Arc VMAT dose plans were generated for these twelve patients and these three different types of plans were evaluated for the quality and compared dosimetrically. RESULT(S): M-4Arc VMAT designs exhibited a greater bone marrow sparing when compared with conventional VMATs with respect to volume receiving 5Gy to 35Gy without compromising PTV dose coverage. M-4Arc VMAT plans, the bone marrow volume receiving 30 Gy (V30Gy),40Gy (V40Gy), and mean doses were lower than the C- 4 Arc plan and a similar result was observed for V50(Gy) also when comparing with the standard 2 Arc plan. In modified VMAT plans, the rectum and bladder dose volumes were lower than standard VMAT. Similarly, the bowel bag V35(Gy), V40(Gy), V50(Gy), mean doses. The right and left femoral head doses were reduced significantly when compared to conventional VMAT plans. CONCLUSION(S): The M-4Arc VMAT plans are better than the C-2Arc and C-4Arc VMAT plans for reducing the dose to bone marrow by limiting the MLC field width travel.

Palas, K., et al. (2021). "Effect of supportive care on the psychosocial health status of women who had a miscarriage." Perspectives in Psychiatric Care 57(1): 179-188.
	Purpose: This study aims to determine the effect of individualized care provided based on Swanson's Caring Theory on the grief, depression, anxiety, and stress levels of women who had a miscarriage. Design and Methods: A total of 104 women who experienced a miscarriage were randomized as study (n = 52) and control (n = 52) groups. Findings: The women's physical, emotional, behavioral, and cognitive grief symptoms decreased after receiving Swanson's care (P < .001). Negative feelings about the future, level of depression, and anxiety levels diminished after receiving Swanson's Care (P < .001). Practice Implications: Supportive care and counseling provided after miscarriage were found to contribute to women's psychosocial well-being and to improve their ability to cope with psychological symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Palazzo, A., et al. (2023). "Major adverse cardiac events and cardiovascular toxicity with PARP inhibitors-based therapy for solid tumors: a systematic review and safety meta-analysis." ESMO Open 8(2): 101154.
	Background: Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) provided significant antitumor activity in various tumors, mainly carrying deleterious mutations of BRCA1/BRCA2 genes. Only few data are available regarding the cardiac and vascular safety profile of this drug class. We carried out a meta-analysis for assessing the incidence and relative risk (RR) of major adverse cardiovascular events (MACEs), hypertension, and thromboembolic events in patients with solid tumors treated with PARPi-based therapy. Method(s): Prospective studies were identified by searching the Medline/PubMed, Cochrane Library, and ASCO Meeting abstracts. Data extraction was conducted according to the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) statement. Combined odds ratios (ORs), RRs, and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods, depending on studies heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used to carry out statistical analyses. Result(s): Thirty-two studies were selected for the final analysis. The incidence of PARPi-related MACEs of any and high grade was 5.0% and 0.9%, respectively, compared with 3.6% and 0.9% in the control arms, corresponding to a significant increased risk of MACEs of any grade (Peto OR 1.62; P = 0.0009) but not of high grade (P = 0.49). The incidence of hypertension of any grade and high grade was 17.5% and 6.0% with PARPi, respectively, compared with 12.6% and 4.4% in the controls. Treatment with PARPi significantly increased the risk of hypertension of any grade (random-effects, RR = 1.53; P = 0.03) but not of high grade (random-effects, RR = 1.47; P = 0.09) compared with controls. Finally, PARPi-based therapies significantly increased the risk of thromboembolic events of any grade (Peto OR = 1.49, P = 0.004) and not of high grade (Peto OR = 1.31; P = 0.13) compared with controls. Conclusion(s): PARPi-based therapy is associated with a significantly increased risk of MACEs, hypertension, and thromboembolic events of any grade compared with controls. The lack of a significant increased risk of high-grade events together with the absolute low incidence of these adverse events led not to consider routine cardiovascular monitoring as recommended in asymptomatic patients.Copyright © 2023 The Authors

Paljk, I., et al. (2022). "Cervical cerclage after prior uterine and cervical surgery." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(25): 7360-7362.
	Objective: To evaluate cerclage placement after uterine and cervical surgery.; Patients and Methods: We compared patients with a prior uterine surgery (with or without cervical surgery) with women having a cerclage for the "classical" indications. Under the classical indications fall history of one or more second-trimester pregnancy losses related to painless cervical dilation, prior cerclage due to painless cervical dilation in the second trimester, painless cervical dilation in the second trimester, ultrasonographic finding with a history of prior preterm birth, prior spontaneous preterm birth at less than 34 weeks of gestation and short cervical length (less than 25 mm) before 24 weeks of gestation.; Results: Forty-seven (44.8%) patients had uterine surgery whereas 58 (55.2%) had the "classical" indications for cerclage. The risk of birth at <37 weeks and birth weight <2500 g was similar, but lower for cerclage after previous uterine/cervical surgery for births >37 weeks (OR 0.3, 95% CI 0.1, 0.8) and hence, for birth weights >2500 g (OR 0.4, 95% CI 0.2-0.9). Both groups had similar incidence of preterm rupture of membranes, chorioamnionitis, need for induction of labor, cesarean births as well as low Apgar scores and admission rates to the NICU.; Conclusions: The major goals of reducing births at <37 weeks and low birth weight of <2500 g are achievable with a cerclage in patients with a prior uterine/cervical surgery as it is in patients with a "classical" indication for cerclage placement.

Palmer, M. J., et al. (2020). "Targeted client communication via mobile devices for improving maternal, neonatal, and child health." Cochrane Database of Systematic Reviews(8).
	- Background The global burden of poor maternal, neonatal, and child health (MNCH) accounts for more than a quarter of healthy years of life lost worldwide. Targeted client communication (TCC) via mobile devices (MD) (TCCMD) may be a useful strategy to improve MNCH. Objectives To assess the effects of TCC via MD on health behaviour, service use, health, and well‐being for MNCH. Search methods In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. Selection criteria We included randomised controlled trials that assessed TCC via MD to improve MNCH behaviour, service use, health, and well‐being. Eligible comparators were usual care/no intervention, non‐digital TCC, and digital non‐targeted client communication. Data collection and analysis We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross‐checked by a second. Main results We included 27 trials (17,463 participants). Trial populations were: pregnant and postpartum women (11 trials conducted in low‐, middle‐ or high‐income countries (LMHIC); pregnant and postpartum women living with HIV (three trials carried out in one lower middle‐income country); and parents of children under the age of five years (13 trials conducted in LMHIC). Most interventions (18) were delivered via text messages alone, one was delivered through voice calls only, and the rest were delivered through combinations of different communication channels, such as multimedia messages and voice calls. Pregnant and postpartum women TCCMD versus standard care For behaviours, TCCMD may increase exclusive breastfeeding in settings where rates of exclusive breastfeeding are less common (risk ratio (RR) 1.30, 95% confidence intervals (CI) 1.06 to 1.59; low‐certainty evidence), but have little or no effect in settings where almost all women breastfeed (low‐certainty evidence). For use of health services, TCCMD may increase antenatal appointment attendance (odds ratio (OR) 1.54, 95% CI 0.80 to 2.96; low‐certainty evidence); however, the CI encompasses both benefit and harm. The intervention may increase skilled attendants at birth in settings where a lack of skilled attendants at birth is common (though this differed by urban/rural residence), but may make no difference in settings where almost all women already have a skilled attendant at birth (OR 1.00, 95% CI 0.34 to 2.94; low‐certainty evidence). There were uncertain effects on maternal and neonatal mortality and morbidity because the certainty of the evidence was assessed as very low. TCCMD versus non‐digital TCC (e.g. pamphlets) TCCMD may have little or no effect on exclusive breastfeeding (RR 0.92, 95% CI 0.79 to 1.07; low‐certainty evidence). TCCMD may reduce 'any maternal health problem' (RR 0.19, 95% CI 0.04 to 0.79) and 'any newborn health problem' (RR 0.52, 95% CI 0.25 to 1.06) reported up to 10 days postpartum (low‐certainty evidence), though the CI for the latter includes benefit and harm. The effect on health service use is unknown due to a lack of studies. TCCMD versus digital non‐targeted communication No studies reported behavioural, health, or well‐being outcomes for this comparison. For use of health services, there are uncertain effects for the presence of a skilled attendant at birth due to very low‐certainty evidence, and the intervention may make little or no difference to attendance for antenatal influenza vaccination (RR 1.05, 95% CI 0.71 to 1.58), though the CI encompasses both benefit and harm (low‐certainty evidence). Pregnant and postpartum women living with HIV TCCMD versus standard care For behaviours, TCCMD may make little or no difference to maternal and infant adherence to antiretroviral (ARV) therapy (low‐certainty evidence). For health service se, TCC mo ile telephone reminders may increase use of antenatal care slightly (mean difference (MD) 1.5, 95% CI –0.36 to 3.36; low‐certainty evidence). The effect on the proportion of births occurring in a health facility is uncertain due to very low‐certainty evidence. For health and well‐being outcomes, there was an uncertain intervention effect on neonatal death or stillbirth, and infant HIV due to very low‐certainty evidence. No studies reported on maternal mortality or morbidity. TCCMD versus non‐digital TCC The effect is unknown due to lack of studies reporting this comparison. TCCMD versus digital non‐targeted communication TCCMD may increase infant ARV/prevention of mother‐to‐child transmission treatment adherence (RR 1.26, 95% CI 1.07 to 1.48; low‐certainty evidence). The effect on other outcomes is unknown due to lack of studies. Parents of children aged less than five years No studies reported on correct treatment, nutritional, or health outcomes. TCCMD versus standard care Based on 10 trials, TCCMD may modestly increase health service use (vaccinations and HIV care) (RR 1.21, 95% CI 1.08 to 1.34; low‐certainty evidence); however, the effect estimates varied widely between studies. TCCMD versus non‐digital TCC TCCMD may increase attendance for vaccinations (RR 1.13, 95% CI 1.00 to 1.28; low‐certainty evidence), and may make little or no difference to oral hygiene practices (low‐certainty evidence). TCCMD versus digital non‐targeted communication TCCMD may reduce attendance for vaccinations, but the CI encompasses both benefit and harm (RR 0.63, 95% CI 0.33 to 1.20; low‐certainty evidence). No trials in any population reported data on unintended consequences. Authors' conclusions The effect of TCCMD for most outcomes is uncertain. There may be improvements for some outcomes using targeted communication but these findings were of low certainty. High‐quality, adequately powered trials and cost‐effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCCMD. Future studies should measure potential unintended consequences, such as partner violence or breaches of confidentiality. Plain language summary Communicating to pregnant woman and parents through their mobile devices to improve maternal, neonatal, and child health Aim of this review We assessed the effect of sending targeted messages by mobile devices to pregnant women and parents of young children about health and healthcare services. Key messages There are gaps in the evidence regarding the effects of targeted messages by mobile devices to pregnant women and parents of young children about health and healthcare services. Some of these messages may improve some people's health and their use of health services, but others may make little or no difference. The existing evidence is mostly of low or very low certainty. What was studied in the review? Targeted client communication (TCC) is an intervention in which the health system sends information to particular people, based on their health status or other factors specific to that population group. Common types of TCC are text messages reminding people to attend appointments or that offer healthcare information and support. Our review assessed whether TCC can change pregnant women's and parents' behaviour, health service use, health, and well‐being. What happens when pregnant women receive targeted messages by mobile device? Compared to women who get no messages Women may breastfeed more in settings where exclusive breastfeeding is not common. They may also go to more antenatal care appointments. They may use skilled birth attendants more where this is less common. We do not know if the messages affect women's or babies' health because the certainty of the evidence is very low. Compared to women who get messages sent in other ways Women and newborns may have fewer health problems during the first 10 days after birth. The messages may make little or no difference to the number of women who breastfeed. We do not know if they make women u e more heal h services. Compared to women who get untargeted messages The messages may make little or no difference to whether women get influenza vaccines during pregnancy. We do not know if the messages affect women's or babies' health or lead women to use skilled birth attendants more because the evidence is lacking or of very low certainty. What happens when pregnant women living with HIV receive targeted messages by mobile device? Compared to women who get no messages Women may go to slightly more antenatal care appointments. We do not know whether the messages lead more women to give birth in a health facility or improve babies' health because the evidence is of very low certainty. The messages may make little or no difference to whether pregnant women and babies follow antiretroviral (ARV) treatment (used to treat HIV) according to plan. We do not know if the messages affect women's health because the evidence is missing. Compared to women who get messages sent in other ways We do not know what the effect of these messages is because we lack evidence. Compared to women who get untargeted messages More parents may follow their babies' ARV treatment according to plan. We do not know if the messages improve women's or babies' health or their use of services because the evidence is missing. What happens when parents of young children receive targeted messages by mobile device? Compared to parents who get no messages More parents may take their children to healthcare services such as vaccination appointments. But we do not know if the messages improve children's health or their health behaviour because the evidence is missing. Compared to parents who get messages sent in other ways Slightly more parents may take their children to vaccination appointments. The messages may make little or no difference to children's toothbrushing habits. We do not know if the messages affect children's health because the evidence is missing. Compared to parents who get untargeted messages Fewer parents may take their children to vaccination appointments, but this evidence is mixed. We do not know if the messages affect children's health due to lack of evidence. How up‐to‐date is this review? We searched for studies published up to August 2017. We carried out a search update in July 2019 and relevant studies are reported in the 'Characteristics of studies awaiting classification' section.

Palmer, M. J., et al. (2020). "Targeted client communication via mobile devices for improving sexual and reproductive health." Cochrane Database of Systematic Reviews(8).
	- Background The burden of poor sexual and reproductive health (SRH) worldwide is substantial, disproportionately affecting those living in low‐ and middle‐income countries. Targeted client communication (TCC) delivered via mobile devices (MD) (TCCMD) may improve the health behaviours and service use important for sexual and reproductive health. Objectives To assess the effects of TCC via MD on adolescents' knowledge, and on adolescents’ and adults' sexual and reproductive health behaviour, health service use, and health and well‐being. Search methods In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. Selection criteria We included randomised controlled trials of TCC via MD to improve sexual and reproductive health behaviour, health service use, and health and well‐being. Eligible comparators were standard care or no intervention, non‐digital TCC, and digital non‐targeted communication. Data collection and analysis We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross‐checked by a second. We have presented results separately for adult and adolescent populations, and for each comparison. Main results We included 40 trials (27 among adult populations and 13 among adolescent populations) with a total of 26,854 participants. All but one of the trials among adolescent populations were conducted in high‐income countries. Trials among adult populations were conducted in a range of high‐ to low‐income countries. Among adolescents, nine interventions were delivered solely through text messages; four interventions tested text messages in combination with another communication channel, such as emails, multimedia messaging, or voice calls; and one intervention used voice calls alone. Among adults, 20 interventions were delivered through text messages; two through a combination of text messages and voice calls; and the rest were delivered through other channels such as voice calls, multimedia messaging, interactive voice response, and instant messaging services. Adolescent populations TCCMD versus standard care TCCMD may increase sexual health knowledge (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.23 to 1.71; low‐certainty evidence). TCCMD may modestly increase contraception use (RR 1.19, 95% CI 1.05 to 1.35; low‐certainty evidence). The effects on condom use, antiretroviral therapy (ART) adherence, and health service use are uncertain due to very low‐certainty evidence. The effects on abortion and STI rates are unknown due to lack of studies. TCCMD versus non‐digital TCC (e.g. pamphlets) The effects of TCCMD on behaviour (contraception use, condom use, ART adherence), service use, health and wellbeing (abortion and STI rates) are unknown due to lack of studies for this comparison. TCCMD versus digital non‐targeted communication The effects on sexual health knowledge, condom and contraceptive use are uncertain due to very low‐certainty evidence. Interventions may increase health service use (attendance for STI/HIV testing, RR 1.61, 95% CI 1.08 to 2.40; low‐certainty evidence). The intervention may be beneficial for reducing STI rates (RR 0.61, 95% CI 0.28 to 1.33; low‐certainty evidence), but the confidence interval encompasses both benefit and harm. The effects on abortion rates and on ART adherence are unknown due to lack of studies. We are uncertain whether TCCMD results in unintended consequences due to lack of evidence. Adult populations TCCMD versus standard care For health behaviours, TCCMD may modestly increase contraception use at 12 months (RR 1.17, 95% CI 0.92 to 1.48) and may reduce repeat abortion (RR 0.68 95% CI 0.28 to 1.66), though the confidence interval encompasses benefit and harm (low‐certainty evidence). The effect o condom us is uncertain. No study measured the impact of this intervention on STI rates. TCCMD may modestly increase ART adherence (RR 1.13, 95% CI 0.97 to 1.32, low‐certainty evidence, and standardised mean difference 0.44, 95% CI ‐0.14 to 1.02, low‐certainty evidence). TCCMD may modestly increase health service utilisation (RR 1.17, 95% CI 1.04 to 1.31; low‐certainty evidence), but there was substantial heterogeneity (I 2 = 85%), with mixed results according to type of service utilisation (i.e. attendance for STI testing; HIV treatment; voluntary male medical circumcision (VMMC); VMMC post‐operative visit; post‐abortion care). For health and well‐being outcomes, there may be little or no effect on CD4 count (mean difference 13.99, 95% CI ‐8.65 to 36.63; low‐certainty evidence) and a slight reduction in virological failure (RR 0.86, 95% CI 0.73 to 1.01; low‐certainty evidence). TCCMD versus non‐digital TCC No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may modestly increase in service attendance overall (RR: 1.12, 95% CI 0.92‐1.35, low certainty evidence), however the confidence interval encompasses benefit and harm. TCCMD versus digital non‐targeted communication No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may increase service utilisation overall (RR: 1.71, 95% CI 0.67‐4.38, low certainty evidence), however the confidence interval encompasses benefit and harm and there was considerable heterogeneity (I 2 = 72%), with mixed results according to type of service utilisation (STI/HIV testing, and VMMC). Few studies reported on unintended consequences. One study reported that a participant withdrew from the intervention as they felt it compromised their undisclosed HIV status. Authors' conclusions TCCMD may improve some outcomes but the evidence is of low certainty. The effect on most outcomes is uncertain/unknown due to very low certainty evidence or lack of evidence. High quality, adequately powered trials and cost effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCC delivered by mobile devices. Given the sensitivity and stigma associated with sexual and reproductive health future studies should measure unintended consequences, such as partner violence or breaches of confidentiality. Plain language summary Communicating to young people and adults through their mobile devices to improve sexual and reproductive health Aim of this review We assessed the effect of sending targeted messages by mobile devices to young people and adults about their sexual and reproductive health (SRH). Sexually transmitted infections (STIs) and unintended pregnancies are important causes of illness and early death worldwide. Key messages There are gaps in the evidence regarding the effects of targeted messages by mobile devices to young people and adults about their SRH. These types of messages may have benefits in a few areas. However, the existing evidence is often of low or very low certainty. What was studied in the review? Targeted client communication (TCC) is an intervention in which the health system sends information to particular people, based on their health status or other factors specific to that population group. Common types of TCC are text messages that remind people to go to appointments or that offer healthcare information and support. Our review assessed whether TCC can change people’s behaviour, use of health services, and health and well‐being. We focused on communication about SRH to young people (aged 10 to 24 years), and to adults. What happens when young people receive targeted messages by mobile device? Compared to people who get no messages Young people may have better SRH knowledge and may use contraceptives slightly more. We don't know if the messages affect young people's condom use; use of SRH services; or the number testing positive for STIs, needing abortions, or adhering o HIV medication, because the evidence is missing or of very low certainty. Compared to people who get messages sent in other ways We do not know what the effect of the messages is because the evidence is missing. Compared to people who get untargeted messages We don't know whether the messages improve SRH knowledge or increase condom or contraceptive use because the certainty of the evidence is very low. The messages may reduce the number of people who get STIs (but it is possible they increase, or make little or no difference to, STIs). The messages may increase the number of young people who attend services for testing for STIs/HIV. We don't know whether the messages affect the number of young people having abortions or help them to take their HIV medication because the evidence is missing. We are uncertain if the messages lead to more unintended consequences among young people than no messages, or other types of communication. What happens when adults receive targeted messages by mobile device? Compared to people who get no messages The messages may slightly increase contraceptive use. They may also reduce the number of adults who need repeated abortions, although it is also possible they increase, or make little or no difference to, the number of abortions. We don't know whether the messages affect adults' condom use or the number of STIs because the evidence is of very low certainty, or missing. The messages may slightly increase adults' adherence to HIV medication among adults with HIV, but may make little or no difference to CD4 count and slightly improve viral load. The messages may slightly increase adults' use of SRH services overall, but results were mixed according to type of health service. Compared to people who get messages sent in other ways Adults receiving messages may attend SRH services more overall, but the evidence is mixed. We do not know what the effect of messages is on other behaviours and health because we lack evidence. Compared to people who get untargeted messages Adults receiving messages may attend SRH services more overall, but the evidence is mixed. We don't know what the effect of messages is on other behaviours and health because we lack evidence. We are uncertain if the messages lead to more unintended consequences among adults than no messages, or other types of communication. How up‐to‐date is this review? We searched for studies that had been published up to August 2017. We carried out a search update in July 2019 and relevant studies are reported in the 'Characteristics of studies awaiting classification' section.

Palmieri, A., et al. (2022). "Extracorporeal shock wave therapy in association with bromelain and escin for the management of patients affected by chronic prostatitis/chronic pelvic pain syndrome." Biomedical reports 18(1): 7.
	Extracorporeal shock wave therapy (ESWT) has been purposed for the management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with encouraging results. Phytotherapeutic compounds have been used in everyday clinical practice for patients with CP/CPSS due to their anti-inflammatory properties. The present study aimed to investigate the effects of ESWT in association with the use of bromelain and escin extracts in patients with CP/CPSS. For this purpose, 95 patients with a clinical diagnosis of CP/CPSS were enrolled in the study. The patients were randomly allocated to either the ESWT plus bromelain and escin group (group A; n=48) or the ESWT only group (group B; n=47). A total of five weekly ESWT treatment sessions were administered alone or in combination with bromelain and escin. Each session consisted of 3,000 focused shock waves. Doses of 160 and 500 mg/day bromelain and escin were administered respectively for 5 weeks. The changes in urinary symptoms, pain and quality of life were considered the main outcome measures and were assessed at baseline, and at 4, 12 and 24 weeks of follow-up. Urinary symptoms, pain and quality of life were evaluated using the international prostatic symptoms score (IPSS), visual analog scale (VAS) and the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). After 4 weeks, the mean VAS score, mean IPSS and mean satisfaction rate score had significantly improved in patients receiving ESWT plus bromelain and escin. After 12 weeks, the mean IPSS and mean satisfaction rate score were stable in the ESWT plus bromelain and escin group, while the mean VAS score was significantly lower when compared with the baseline values in both groups. On the whole, the present study demonstrates that in patients affected by CP/CPPS, treatment with ESWT plus bromelain and escin leads to pain resolution, and both treatments improve the IPSS, VAS and NIH-CPSI results.; Competing Interests: The authors declare that they have no competing interests. (Copyright: © Palmieri et al.)

Palomba, S., et al. (2023). "Interventions to prevent or reduce the incidence and severity of ovarian hyperstimulation syndrome: a systematic umbrella review of the best clinical evidence." Reproductive biology and endocrinology : RB&E 21(1): 67.
	Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threating iatrogenic complication of the early luteal phase and/or early pregnancy after in vitro fertilization (IVF) treatment. The aim of the current study was to identify the most effective methods for preventing of and reducing the incidence and severity of OHSS in IVF patients. A systematic review of systematic reviews of randomized controlled trials (RCTs) with meta-analysis was used to assess each potential intervention (PROSPERO website, CRD 268626) and only studies with the highest quality were included in the qualitative analysis. Primary outcomes included prevention and reduction of OHSS incidence and severity. Secondary outcomes were maternal death, incidence of hospital admission, days of hospitalization, and reproductive outcomes, such as incidence of live-births, clinical pregnancies, pregnancy rate, ongoing pregnancy, miscarriages, and oocytes retrieved. A total of specific interventions related to OHSS were analyzed in 28 systematic reviews of RCTs with meta-analyses. The quality assessment of the included studies was high, moderate, and low for 23, 2, and 3 studies, respectively. The certainty of evidence (CoE) for interventions was reported for 37 specific situations/populations and resulted high, moderate, and low-to-very low for one, 5, and 26 cases, respectively, while it was not reported in 5 cases. Considering the effective interventions without deleterious reproductive effects, GnRH-ant co-treatment (36 RCTs; OR 0.61, 95% C 0.51 to 0.72, n = 7,944; I 2 = 31%) and GnRH agonist triggering (8 RCTs; OR 0.15, 95% CI 0.05 to 0.47, n = 989; I 2 = 42%) emerged as the most effective interventions for preventing OHSS with a moderate CoE, even though elective embryo cryopreservation exhibited a low CoE. Furthermore, the use of mild ovarian stimulation (9 RCTs; RR 0.26, CI 0.14 to 0.49, n = 1,925; I 2 = 0%), and dopaminergic agonists (10 RCTs; OR 0.32, 95% CI 0.23 to 0.44, n = 1,202; I 2 = 13%) coadministration proved effective and safe with a moderate CoE. In conclusion, the current study demonstrates that only a few interventions currently can be considered effective to reduce the incidence of OHSS and its severity with high/moderate CoE despite the numerous published studies on the topic. Further well-designed RCTs are needed, particularly for GnRH-a down-regulated IVF cycles. (© 2023. The Author(s).)

Pamela da Silva, M., et al. (2021). "Non-ablative radiofrequency in the treatment of pelvic dysfunctions."
	
Pan, M., et al. (2023). "Drugs for the treatment of postmenopausal symptoms: Hormonal and non-hormonal therapy." Life Sciences 312: 121255.
	Postmenopausal symptoms are systemic symptoms associated with estrogen deficiency after menopause. At present, treatments for postmenopausal symptoms include hormonal therapy (HT) and non-HT. However, the optimal regimen for balancing the benefits and risks remains unclear. This article reviewed the characteristics, regimens, and side effects of drugs used in hormonal and non-HT. However, HT is still the most effective treatment with safety in early initiation since menopause onset. Nevertheless, it is essential to evaluate the risks of related chronic diseases and customize individualized treatments. Possible estetrol preparations and more types of Tissue Selective Estrogen Complex formulations are potential directions of drug development in the future of HT. Regarding non-HT, fezolinetant, currently in phase III clinical trials, is poised to become a first-in-class therapy for vasomotor symptoms. Ospemifene, dehydroepiandrosterone (DHEA), and vaginal lasers can also be used for moderate-to-severe genitourinary syndrome of menopause. Recent data suggest a superior efficacy and safety of vaginal lasers, but more validated evidence of long-term tolerability is needed to respond to the United States Food and Drug Administration warning. Herbal medication commonly used in Asia is effective in alleviating menopausal symptoms; however, its adverse effects still require more detailed reports and standardized observation methods. This review contributes to a better understanding of drugs for the treatment of postmenopausal symptoms and provides useful information for clinical drug selection.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pan, S. Y., et al. (2021). "Effect of Dingkundan in Adjuvant Treatment of Patients with Radiotherapy and Chemotherapy After Endometrial Carcinoma Operation."  27(5): 111‐116.
	Objective： To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms，quality of life，immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma（EC）operation. Method： Patients were divided into control group（82 cases）and observation group（86 cases）according to random number table. A total of 75 patients in control group completed the study（4 patients fell off or lose visit，and 3 patients were eliminated），while 77 patients in observation group completed the study（5 patients fell off or lose visit，and 4 patients were deleted）. After operation，patients got brachytherapy，external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan，1 pill/time，2 times/day，and those in observation group got Dingkundan，7 g/time，2 times/day. The course of treatment lasted for 4 months，and long‐time follow‐up data was recorded. Before treatment，and at the second and fourth month after treatment，deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded，and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets（CD3+ ，CD4+ ，CD8+ and CD4+ /CD8+ ）were detected，European collaborative quality of life Cancer Core Scale（EORTC QLQ‐C30）was evaluated，and expressions of pce125（CA125）， epididymis protein 4（HE4），Dickkopf‐related protein‐1（DKK1），vascular endothelial growth factor（VEGF）， matrix metalloproteinase‐9（MMP‐9）and transforming growth factor‐β1（TGF‐β1 ）were tested before and after treatment. The follow‐up was made for every three months，and the progression（recurrence/metastasis）of patients was recorded. Result：Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment（P<0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression，gastrointestinal toxicity，neurotoxicity were lower than those in control group（P<0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ‐C30 in observation group were higher than those in control group（P<0.01），and scores of three symptom dimensions were lower than those in control group（P<0.01）. Levels of CD3+ ，CD4+ and CD4+ /CD8+ were higher than those in the control group（P<0.01），and CD8+ was lower than those in the control group（P<0.01）. Levels of CA125，HE4，DKK1，VEGF，MMP‐9 and TGF‐β1 were lower than those in the control group （P<0.01）. The disease progression rate in observation group was 18.18%（14/77），which was lower than 33.33%（25/75）in control group（χ2 =4.572，P<0.05）. Conclusion： In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation，Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy，improve the quality of life and immune function，inhibit the expression of tumor markers and tumor growth factor，delay the progression of tumor and improve the prognosis.

Pan, X. B., et al. (2024). "Efficacy of treatment patterns based on concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma." BMC Cancer 24(1): 106.
	Purpose: To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). Material(s) and Method(s): Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods. Result(s): A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41-2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45-12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14-25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29-2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55-42.26; P = 0.157) compared to CCRT. Conclusion(s): AC did not improve survival in patients with stage IIB CSCC receiving CCRT.Copyright © 2023, The Author(s).

Pan, Y., et al. (2022). ""Let's see what happens:"-Women's experiences of open-label placebo treatment for menopausal hot flushes in a randomized controlled trial." PloS One 17(11): e0276499.
	Open-label (honestly prescribed) placebos are an ethical way to evoke placebo effects in patients. As part of a mixed-methods study, we conducted in-depth interviews with eight menopausal women who underwent and benefitted from open-label placebo treatment in a randomized-controlled trial of hot flushes. Data were analyzed using Interpretative Phenomenological Analysis. We found that the women had low expectations about the placebo treatment yet endorsed what they referred to as "hope" and openness to "see what happens". Recording hot flushes via the symptom diary was viewed as a valuable opportunity for self-examination and appraising outcomes. Receiving relief from the placebo treatment empowered women and enhanced their sense of control and agency. In summary, participants' initial openness towards placebos, their hopes to get better, monitoring symptoms closely, and taking the initiative to address symptoms were components of a positive open-label placebo experience.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2022 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pan, Y., et al. (2023). "Correlation between different endometrial preparation protocols and pregnancy outcome of frozen embryo transfer in patients with polycystic ovary syndrome: a retrospective study." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 39(1): 2217260.
	Objective: We retrospectively analyzed the correlation between different endometrial preparation protocols and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) who underwent frozen embryo transfer (FET).; Methods: A total of 200 PCOS patients who underwent FET were divided into HRT group ( n = 65), LE group ( n = 65), GnRHa + HRT group ( n = 70) according to different endometrial preparation protocols. The endometrial thickness on the day of endometrial transformation, the number of embryos transferred, and the number of high-quality embryos transferred were compared among the three groups. The pregnancy outcomes of FET in the three groups were compared and analyzed, and a further multivariate logistic regression model was used to analyze the factors influencing FET pregnancy outcomes in PCOS patients.; Results: Endometrial thickness on the day of endometrial transformation, clinical pregnancy rate and live birth rate in GnRHa + HRT group were higher than those in the HRT group and LE group. The results of multivariate regression analysis showed that the pregnancy outcome of PCOS patients undergoing FET was significantly associated with the patient's age, endometrial preparation protocols, number of embryos transferred, endometrial thickness, and duration of infertility.; Conclusion: Compared with HRT or LE alone, GnRHa + HRT protocol results in higher levels of endometrial thickness on the day of endometrial transformation, clinical pregnancy rate, and live birth rate. Female age, endometrial preparation protocols, number of embryos transferred, endometrial thickness, and duration of infertility are determined as factors influencing pregnancy outcomes in PCOS patients undergoing FET.

Pan, Y., et al. (2023). "Spatholobi caulis: A systematic review of its traditional uses, chemical constituents, biological activities and clinical applications." Journal of Ethnopharmacology 317: 116854.
	Ethnopharmacological Relevance: Spatholobi caulis (SC), the dried vine stem of Spatholobus suberectus Dunn, is known as Ji Xue Teng in China, and has long been used as traditional Chinese medicine (TCM) to treat anaemia, menstrual abnormalities, rheumatoid arthritis, purpura, etc. AIM OF THE REVIEW: The aim of this review is to provide a systematic and updated summary of the traditional uses, chemical constituents, biological activities and clinical applications of SC. In addition, several suggestions for future research on SC are also proposed.; Materials and Methods: Extensive information and data on SC were obtained from electronic databases (ScienceDirect, Web of Science, PubMed, CNKI, Baidu Scholar, Google Scholar, ResearchGate, SpringerLink and Wiley Online). Additional information was collected from Ph.D. and MSc dissertations, published books, and classic material medica.; Results: To date, phytochemical studies have revealed that approximately 243 chemical ingredients have been isolated from SC and identified, including flavonoids, glycosides, phenolic acids, phenylpropanoids, volatile oils, sesquiterpenoids and other compounds. Many studies have indicated that extracts and pure constituents from SC possess a wide spectrum of in vitro and in vivo pharmacological effects, such as anti-tumour, haematopoietic, anti-inflammatory, antidiabetic, antioxidant, antiviral and antibacterial effects, as well as other activities. SC could be applied to the treatment of leukopenia, aplastic anemic, endometriosis, etc. according to the clinical reports. The traditional efficacies of SC is due to the biological functions of its chemical compounds, especially flavonoids. However, research investigating the toxicological effects of SC is relatively limited.; Conclusions: SC is widely used in TCM formulae and its some traditional efficacies has been confirmed by extensive recent pharmacological and clinical studies. Most the biological activities of the SC may be attributed to flavonoids. However, in-depth studies on the molecular mechanisms of the effective ingredients and extracts of SC are limited. Further systematic studies focusing on pharmacokinetics, toxicology and quality control are needed to ensure the effective and safe application of SC.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pan, Y., et al. (2019). "Non-concealed placebo treatment for menopausal hot flushes: Study protocol of a randomized-controlled trial." Trials 20(1): 508.
	Background: Beneficial effects of placebos are high in double-blind hot flush trials. Studies in various conditions suggest that honestly prescribed placebos may elicit symptom improvement.; Objective: To determine whether open label placebo (OLP) treatment is efficacious in alleviating hot flushes among peri- and postmenopausal women.; Methods/design: In this assessor-blinded, randomized-controlled trial, n = 100 women experiencing five or more daily hot flushes of at least moderate severity and bothersomeness are assigned 1:1 to a 4-week OLP treatment or no treatment. To explore the duration and maintenance of placebo effects, the OLP group is randomized a second time to either discontinue or continue the OLP treatment for another 4 weeks. All participants receive a briefing about placebo effects and study visits at baseline, post-treatment (4 weeks), and follow-up (8 weeks, OLP group only). Qualitative interviews about subjective experiences with the OLP treatment are conducted. Primary outcomes are differences between the OLP and the no-treatment group in the hot flush composite score (frequency × severity), and bothersomeness of hot flushes as assessed with the Hot Flush Rating Scale at post-treatment. Secondary outcomes include hot flush frequency, health-related quality of life, global improvement, and the number of responders at post-treatment. Data are analyzed by fitting (generalized) linear mixed models. An exploratory analysis of maintenance and duration is performed including follow-up data.; Discussion: This trial will contribute to the evaluation of OLP treatments in clinical practice and further our understanding about the magnitude of placebo effects in hot flush treatments.; Trial Registration: Clinicaltrials.gov, NCT03838523 . Retrospectively registered on February 12th, 2019. The first patient was enrolled on October 10th, 2018.

Pan, Y., et al. (2021). "Effect of comprehensive care on the negative emotions and life quality in parturients with postpartum depression and gestational hypertension." American journal of translational research 13(6): 7228-7234.
	OBJECTIVE: To investigate the efficacy of comprehensive care during the nursing process of parturients with gestational hypertension and postpartum depression. METHODS: This prospective study recruited 70 patients with gestational hypertension concurrent with postpartum depression, and the patients were randomly divided into a control group (35 patients received routine care) and an observation group (35 patients, treated by comprehensive care). Indicators including psychological condition, life quality, thyroid function, the incidence of eclampsia, and nursing satisfaction were recorded and compared before intervention (at the diagnosis of postpartum depression) and after intervention (three months after delivery) in the two groups. RESULTS: The Hamilton Anxiety (HAMA) Scale and Hamilton Depression (HAMD) Scale scores were decreased in both groups after care intervention. Scores of Quality of Life Comprehensive Assessment Questionnaire (GQOLI-74) in all dimensions were higher after intervention than those of before intervention, and improvement was greater in the observation group (P<0.05). The levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine after the intervention were higher than those before the intervention in the two groups, and the increase in the observation group was greater significant than that in the control group (P<0.05). The incidence of postpartum eclampsia in the observation group was lower than that of the control group, and the nursing satisfaction of patients in the observation group was higher than that of the control group (both P<0.05). CONCLUSION: Comprehensive care effectively relieved the abnormal psychological condition, promoted thyroid function, reduced the risk of postpartum eclampsia and improved the quality of life in patients with gestational hypertension and postpartum depression.

Pan Yifang, E., et al. (2023). "Real-World Efficacy and Safety of PARP Inhibitors in Recurrent Ovarian Cancer Patients With Somatic BRCA and Other Homologous Recombination Gene Mutations." The Annals of Pharmacotherapy 57(10): 1162-1171.
	Background: Real-world data regarding the use of poly (ADP-ribose) polymerase (PARP) inhibitors in recurrent ovarian cancer patients with non-BRCA homologous recombination (HR) mutations or somatic BRCA mutations are lacking.; Objective: The purpose of our study is to evaluate the response rate, duration of treatment, time to progression (TTP), and toxicities of olaparib, niraparib, and rucaparib in somatic BRCAm and non-BRCA HR-mutated patients.; Methods: This was a retrospective study using the electronic medical record to identify patients across our health system who were initiated on a PARP inhibitor for ovarian cancer between December 2014 and December 2019. Patients were screened for the presence of a somatic BRCA1/2 mutation or a mutation in non-BRCA HR genes. Data were collected via chart review.; Results: For the efficacy analysis, 8 patients had somatic BRCA mutations and 12 patients had HR mutations. The overall response rate (ORR) was 50% for BRCA-mutated (BRCAm) patients and 9.1% for non-BRCA HR-mutated (non-BRCA HRm) patients. 72.7% of patients with non-BRCA HR mutations had stable disease. The duration of therapy ranged from 2 to 66 months. The median TTP was 9.5 months. Overall, 66.7% of patients in the entire cohort started on a reduced dose of PARP inhibitor. Dose reductions due to AEs were observed in 52.4% of patients, while AEs requiring treatment interruption occurred in 61.9%.; Conclusion and Relevance: We found that PARP inhibitors provided stable disease in a high proportion of recurrent ovarian cancer patients who had pathogenic HR mutations, with toxicities comparable to major trials. Patients with non-BRCA HR and somatic BRCA mutations could benefit from PARP inhibitors.

pan, z. and q. su (2023). "The value of G-CSF in women with a history of embryo transfer failure: a systematic review and meta-analysis."
	
pan, z. and l. xu (2021). "Different regimens of hormone therapy for improving sleep disturbance in perimenopausal and postmenopausal women: a systematic review and meta-analysis."
	
Panda, S., et al. (2020). "Treatment planning comparison of volumetric modulated arc therapy employing a dual-layer stacked multi-leaf collimator and helical tomotherapy for cervix uteri." Radiation oncology (London, England) 15(1): 22.
	Purpose: To ascertain the dosimetric performance of a new delivery system (the Halcyon system, H) equipped with dual-layer stacked multi-leaf collimator (MLC) for risk-adapted targets in cervix uteri cancer patients compared to another ring-based system in clinical operation (Helical Tomotherapy, HT).; Methods: Twenty patients were retrospectively included in a treatment planning study (10 with positive lymph nodes and 10 without). The dose prescription (45Gy to the primary tumour volume and a simultaneously integrated boost up to 55Gy for the positive patients) and the clinical planning objectives were defined consistently as recommended by an ongoing multicentric clinical trial. Halcyon plans were optimised for the volumetric modulated arc therapy. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms.; Results: The coverage of the primary and nodal target volumes was comparable for both techniques and both subsets of patients. The primary planning target volume (PTV) receiving at least 95% of the prescription isodose ranged from 97.2 ± 1.1% (node-negative) to 99.1 ± 1.2% (node-positive) for H and from 96.5 ± 1.9% (node-negative) to 98.3 ± 0.9% (node-positive) for HT. The uncertainty is expressed at one standard deviation from the cohort of patient per each group. For the nodal clinical target volumes, the dose received by 98% of the planning target volume ranged 55.5 ± 0.1 to 56.0 ± 0.8Gy for H and HT, respectively. The only significant and potentially relevant differences were observed for the bowels. In this case, V 40Gy resulted 226.3 ± 35.9 and 186.9 ± 115.9 cm 3 for the node-positive and node-negative patients respectively for Halcyon. The corresponding findings for HT were: 258.9 ± 60.5 and 224.9 ± 102.2 cm 3 . On the contrary, V 15Gy resulted 1279.7 ± 296.5 and 1557.2 ± 359.9 cm 3 for HT and H respectively for node-positive and 1010.8 ± 320.9 versus 1203.8 ± 332.8 cm 3 for node-negative.; Conclusion: This retrospective treatment planning study, based on the dose constraints derived from the Embrace II study protocol, suggested the essential equivalence between Halcyon based and Helical Tomotherapy based plans for the intensity-modulated rotational treatment of cervix uteri cancer. Different levels of sparing were observed for the bowels with H better protecting in the high-dose region and HT in the mid-low dose regions. The clinical impact of these differences should be further addressed.

Panda, S. R., et al. (2023). "Efficacy of In-utero Infusion of Autologous Platelet Rich Plasma Therapy in Women with Recurrent Implantation Failure: A Systematic Review and Meta-analysis of Randomised Controlled Trials." Journal of Clinical and Diagnostic Research 17(2): QC01-QC05.
	Introduction: In-utero infusion of autologous Platelet Rich Plasma (PRP) is found to be a novel approach to address the thin, non receptive endometrium leading to recurrent implantation failure. Aim(s): To estimate the efficacy of intrauterine PRP infusion in subfertile females affected with recurrent implantation failure via the conduction of a systematic review and meta-analysis of the available Randomised Controlled Trials (RCTs). Material(s) and Method(s): A systematic literature search was done in electronic databases like Medline (through PubMed), Embase, Scopus, Web of Science, and Cochrane database from January 2000 to November 2020 using keywords like "In-vitro Fertilisation" OR "IVF" OR "Intracytoplasmic sperm injection" OR "ICSI" OR "Embryo transfer" AND "Platelet rich plasma" OR "PRP" OR "Autologous platelet rich plasma" OR "Platelet rich plasma" and "recurrent implantation failure". The randomised controlled trials, comparing intrauterine infusion of PRP versus no intervention or placebo in a study population of subfertile women with recurrent implantation failure and having medically confirmed pregnancy outcomes like live birth, clinical pregnancy, chemical pregnancy, and miscarriage were included in this systematic review. Studies with inadequate details in the methodology or result section were excluded from this analysis. This meta-analysis involved a pooled data analysis of 335 participants (174 cases and 161 controls) from four RCTs. Result(s): Compared with the control group, patients in the PRP group were found to have more beneficial effects in terms of implantation rate (Relative risks: 1.51, 95% Confidence interval: 0.94, 2.44; Heterogeneity: Tau2=0.08; I2=44%; Test for overall effect: Z=1.69, p-value=0.09) and clinical pregnancy (Relative risk: 1.88, 95% CI: 1.17, 3.03; Heterogeneity: Tau2=0.12; I2=51%; Test for overall effect: Z=2.62; p-value=0.009). Conclusion(s): Intrauterine PRP infusion increases the implantation rate and clinical pregnancy rate in women undergoing the frozen embryo transfer cycle.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

Panda, S. R., et al. (2020). "A Systematic Review Evaluating the Efficacy of Intra-Ovarian Infusion of Autologous Platelet-Rich Plasma in Patients With Poor Ovarian Reserve or Ovarian Insufficiency." Cureus 12(12): e12037.
	The emergence of autologous platelet-rich plasma (PRP) therapy reflects a break-through for infertile patients with premature ovarian failure. To study the efficacy of intra-ovarian infusion of autologous PRP on the improvement of ovarian reserve parameters and the subsequent artificial reproductive technique (ART) cycle outcomes in infertile women with poor ovarian reserve or premature ovarian insufficiency, a systematic search in electronic databases like Medline (through PubMed), Embase, Scopus, Web of Science, and Cochrane was done using relevant search terms. Except for case series, case reports, and review articles, all other types of studies, those evaluated for the effects of intra-ovarian infusion of PRP in subfertile women for decreased ovarian reserve (DOR) or premature ovarian insufficiency (POI) were included in our systematic review. The data were extracted from each eligible study and cross-checked by two authors. Intra-ovarian PRP infusion appears to be effective in ovarian rejuvenation, and the results of the subsequent intracytoplasmic sperm injection (ICSI) cycle are encouraging. PRP intervention was found to be beneficial in terms of an improvement in ovarian reserve parameters (increase in serum anti-mullerian hormone or antral follicle count or decrease in serum follicular stimulating hormone). ICSI cycle performance in terms of the total number of oocytes retrieved, number of two-pronuclei embryos, fertilization rate, number of cleavage stage embryos, number of good quality embryos, and cycle cancellation rate were found to be improved after intra-ovarian PRP infusion as compared to their previous cycle without PRP infusion.

Pandey, D., et al. (2023). "Intrauterine instillation of autologous platelet-rich plasma in infertile females with thin endometrium undergoing intrauterine insemination: an open-label randomized controlled trial." AJOG Global Reports 3(2): 100172.
	Background: Thin endometrium in infertile female patients has always been a clinical challenge for the treating reproductive physicians.; Objective: This study aimed to evaluate the effect of intrauterine instillation of autologous platelet-rich plasma on endometrial thickness and vascularity in infertile female patients with thin endometrium undergoing ovarian stimulation with intrauterine insemination.; Study Design: This prospective randomized control study included 120 women undergoing ovarian stimulation with intrauterine insemination, aged between 21 and 37 years, with persistent thin endometrium (<7 mm) on ≥1 cycle in previous ovarian stimulation cycles, even after conventional treatment with estradiol valerate. The women were randomly assigned to study group A and control group B. Baseline endometrial thickness and endometrial vascularity were noted. Intrauterine instillation of autologous platelet-rich plasma was done on the day of trigger in group A, whereas estradiol valerate was given in group B. Another evaluation of endometrial parameters was done on the day of intrauterine insemination. The cycle was repeated for 3 cycles or until the pregnancy was achieved, whichever occurred earlier. Parameters were noted for both groups. Primary outcomes were the change in endometrial thickness and endometrial vascularity. Secondary outcomes were positive pregnancy rate and clinical pregnancy rate.; Results: In group A, mean pre-platelet-rich plasma endometrial thickness was 4.66±0.79 mm, which significantly increased to 7.47±0.85 mm after platelet-rich plasma instillation ( P <.05) after 3 cycles. This increase was significantly greater than that observed in group B. There was significant increase in endometrial vascularity in group A compared with group B ( P <.05). The positive pregnancy rate and clinical pregnancy rate in group A were 23.73% and 18.64%, respectively, and significantly higher than those in group B.; Conclusion: Autologous platelet-rich plasma is a promising, easily procurable, and novel option for management of infertile females with thin endometrium not responding to conventional treatment. Using it in intrauterine insemination cycles can reduce costs and psychological burden of this subgroup of women by reducing the need for resorting to advanced options such as in vitro fertilization and surrogacy. (© 2023 The Authors.)

Pandit, U., et al. (2022). "Assessment of Maternal and Fetal Outcomes in Pregnancy Complicated by Fibroid Uterus." Cureus 14(2): e22052.
	Background The study aims to assess maternal and fetal outcomes in pregnancy complicated by a fibroid uterus. Materials and methods Sixty-four adult women patients with fibroids in age range of 25-45 years were selected. Fetal and maternal outcomes were recorded. Results Thirty-four patients were in the age group of 25-35 years, and 50 were aged 35-45 years of age. Primigravida was seen in 52 and multigravida in 32. The common types were intramural in 40, submucosal in 16, pedunculated in seven, and subserosal in 21 cases. Size >5 cm was seen in 38 and 2 cm-5 cm in 46 patients. Common symptoms were preterm labor pain in 50, abdominal pain in 12, and urinary tract infection (UTI) in 22 cases. The common sites were the anterior wall fibroid in 42, posterior wall in 22, and lateral wall in 20 cases. Complications reported in our study were premature rupture of membranes (PROMs) in 12, threatened preterm in 11, associated infertility in five, intrauterine growth retardation (IUGR) in two, malpresentation in seven, postpartum hemorrhage (PPH) in four, preterm labor in six, and abruption in eight cases. The difference was observed to be significant (P<0.05). Conclusion Common complications were PROM, threatened preterm, associated infertility, IUGR, malpresentation, PPH, preterm labor, and abruption.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Pandit et al.)

Pando, C., et al. (2023). "9605 Endometrial Ablation for Abnormal Uterine Bleeding in the Setting of Severe Thrombocytopenia." Journal of Minimally Invasive Gynecology 30(11 Supplement): S76-S77.
	Study Objective: To report on the safety of endometrial ablation in patients with severe thrombocytopenia. Design(s): Case Series. Setting(s): Academic, tertiary-care medical center. Patients or Participants: Patient A was a 44-year-old G3P3003 who presented with dyspnea and acute uterine bleeding. Patient was diagnosed with B-cell lymphoma and associated pancytopenia with a platlet nadir of 8 * 103/uL. Patient B was a 44-year-old who presented for acute uterine bleeding in setting of severe aplastic anemia. Patient B had platelet nadir of 10 * 103/uL. Decision was made to proceed with hysteroscopy and endometrial ablation. Intervention(s): Patient A received 20 units of platelets with rise to 42 * 103/uL on day of surgery. She was receiving trimethoprim/sulfamethoxazole, fluconazole, and levofloxacin for neutropenia prophylaxis. No additional preoperative antibiotics given. MAC anesthesia was utilized without a paracervical block. A stitch was placed in the anterior cervix in replacement of a tenaculum. This was tied at the end to avoid leaving open puncture wounds. The cervix was hydrodilated and soft tissue morcellator was used to sample the endometrium. Bipolar radiofrequency endometrial ablation was completed. Total operative time was 28 seconds. Patient B received IVIG, methylprednisolone, and 4 units platelets with no response. Platelets on day of surgery were 11 * 103/uL. Neutropenic prophylaxis regiment consisted of acyclovir, levofloxacin, and voriconazole. Additional preoperative regimen was given with cefazolin and metronidazole. Anesthesia and the procedure were performed in the same fashion with an additional sharp curettage. Total operative time was 19 minutes. Post operative doxycycline was prescribed. Measurements and Main Results: Uterine bleeding stopped in both patients without the need for further interventions for over two years. Conclusion(s): Endometrial ablation can be a safe and feasible approach to surgical management of abnormal uterine bleeding in the setting of severe thrombocytopenia, even in patients refractory to platelet transfusions. These cases demonstrate measures our team took to perform the procedures safely.Copyright © 2023

Pandozzi, C., et al. (2022). "Phytotherapic approach in menopause: light and darkness." Minerva Endocrinology 47(4): 421-436.
	Introduction: Menopause is a critical period of the woman life, characterized by a peculiar modification in estrogens concentration and accompanied by different signs and symptoms. To prevent and contrast unfavorable consequences of menopause, different therapeutic approaches could be evaluated. The hormone replacement therapy (HRT) is the most known, but it has several contraindications. The increasing interest in phytotherapy introduces the necessity for endocrinologist involved in menopause to suggest different therapeutic approaches, considering the state of health of patient and the real efficacy of the drugs. We aim to outline the main phytotherapy treatments to choose in menopause.; Evidence Acquisition: This review is based on focused research of the current literature on PubMed and Scopus such as research databases. We selected 4120 papers through these keywords: "MENOPAUSE" AND "phytotherapy," "natural therapy," "phytoterapy drugs." Then, the literature was scanned selecting English papers of last 10 years (last research on October 1, 2021), excluding reviews. Separately, two researchers MGT and CP examined and read 212 full selected papers. We included clinical trials and randomized clinical trials written in English and excluded duplicates, animal studies and studies with lack of group of interest, non-relevant outcomes, inappropriate methodology. Retrospective studies, case reports, case series, original articles, brief communications, and letter to the editor were included in our research. We furthermore completed our research by the examination of every study's bibliography.; Evidence Synthesis: Phytotherapy involves the use of plants or plant extracts for the treatment of diseases thanks to the activities of their compounds and metabolites. In particular, many of them have an estrogen-like activity and are identified as phytoestrogens, because thanks to their chemical structure are able to bind the estrogen receptors and carry out biological estrogenic or antiestrogenic activities. The supplementing diet with these compounds can ensure an advantage on various aspects of the climacteric syndrome and some of them also have a beneficial impact on cardiovascular risk, bone health and sleep complaint. These substances can be used with safety due to their good tolerability and low rate of side effects. There are no known serious adverse events associated with their consumption, but as a precaution, its use is not recommended during pregnancy and in association with hormonal therapies or in women with hormone responsive cancers.; Conclusions: Phytotherapy must be considered an interesting tool in the treatment of signs and symptoms in selected menopause woman.

Pandurevic, S., et al. (2023). "Efficacy of very low-calorie ketogenic diet with the Pronokal® method in obese women with polycystic ovary syndrome: a 16-week randomized controlled trial." Endocrine connections 12(7).
	Objective: The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age.; Design: Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokal® method (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16.; Results: BMI decreased significantly in both groups and to a major extent in the experimental group (-13.7% vs -5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (-11.4% vs -2.9%), BIA-measured body fat (-24.0% vs -8.1%), and free testosterone (-30.4% vs -12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (-23% vs -13.2%, P > 0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P > 0.05) at the end of the study, respectively.; Conclusion: In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokal® method was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction.; Significance Statements: To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese PCOS women.

Panelli, D. M., et al. (2023). "Associations between physical fitness, depression, and PTSD during pregnancy among U.S. Army soldiers." American Journal of Obstetrics and Gynecology 228(1 Supplement): S121.
	Objective: Depression and post-traumatic stress disorder (PTSD) are prevalent in pregnancy, especially among military members. Strong data suggests these conditions lead to adverse birth outcomes, yet there's a paucity of evidence for effective preventive interventions. Optimizing physical fitness is one potentially promising intervention that has been understudied. We explored baseline associations between pre-pregnancy physical fitness and perinatal mental health conditions in soldiers. Study Design: This was a retrospective cohort study of active-duty U.S. Army soldiers with livebirths between 2011 and 2014. Outcomes were ascertained using diagnosis codes from in- and outpatient care. The exposure was each individual's army physical fitness score from 10-24 months prior to delivery, averaged if there were multiple. The primary outcome was a composite of active depression or PTSD during pregnancy, defined using the presence of a code for either diagnosis within 10 months prior to delivery. Demographic variables were compared between people with higher (>50th percentile) versus lower (< 50th percentile) fitness scores. Multivariable logistic regression models were conducted adjusting for potential confounders, modeling per 10-unit fitness score increments. Result(s): Among 52,055 female active-duty soldiers, 11,986 had eligible livebirths and 4,675 additionally had fitness scores available 10-24 months prior. 361 (7.7%) had depression or PTSD during pregnancy. Demographics varied by fitness scores (Table 1). People with higher fitness scores were less likely to have active depression or PTSD during pregnancy (aOR 0.96, 95% CI 0.93-0.99, Table 2). Findings were similar when examining fitness scores and active depression only (aOR 0.96, 95% CI 0.93-0.99), as well as active PTSD only (aOR 0.97 (0.93-1.00). Conclusion(s): In this cohort of soldiers, for every 10 point increase in pre-pregnancy physical fitness score, the odds of active depression or PTSD during pregnancy decreased by 4%. Physical fitness may be a useful tool to reduce mental health burden in pregnancy. [Formula presented] [Formula presented]Copyright © 2022

Pang, L., et al. (2023). "The safety and effectiveness of laparoscopic anterior sacral ligament suspension combined with dome suspension in the treatment of bladder prolapse after hysterectomy: a retrospective cohort study." Translational Andrology and Urology 12(3): 433-443.
	Background: Laparoscopic anterior sacral ligament suspension combined with dome suspension (L-ASLS + DS) and transperineal whole pelvic floor reconstruction (T-WPFR) are 2 methods for treating bladder prolapse after hysterectomy. In clinical practice, we found that L-ASLS + DS has better safety and effectiveness than T-WPFR, but there is no relevant study comparing the safety and effectiveness of these two methods. We sought to compare the efficacy and safety of L-ASLS + DS and T-WPFR in treating hysterectomy-induced bladder prolapse overa 1-year follow-up period. Method(s): A total 146 patients with bladder prolapse after hysterectomy who attended Shanxi Provincial People's Hospital from January 2011 to January 2022 were included in this study. Patients were divided into study group and control group by voluntary means or economic reasons. In total, 75 patients received L-ASLS + DS surgery and 71 patients received T-WPFR surgery to treat hysterectomy-induced bladder prolapse. The L-ASLS + DS-treated patients comprised the study group, while the T-WPFR-treated patients comprised the control group. The perioperative indicators, curative effect, and postoperative complication rates in the follow-up period were compared between the 2 groups. Result(s): L-ASLS + DS outperformed T-WPFR in terms of the perioperative indicators, and the incidence of postoperative complications in the L-ASLS + DS group was significantly lower than that in the T-WPFR group. Conclusion(s): L-ASLS + DS can be used to effectively treat bladder prolapse after hysterectomy. L-ASLS + DS reduced the incidence of postoperative complications, improved the cure rate, and was shown to be safe. Thus, it is worthy of comprehensive clinical application.Copyright © Translational Andrology and Urology. All rights reserved.

Pang, L.-L., et al. (2021). "Efficacy of High-Intensity Focused Ultrasound Combined With GnRH-a for Adenomyosis: A Systematic Review and Meta-Analysis." Frontiers in Public Health 9: 688264.
	Objective: High-intensity focused ultrasound (HIFU) is an innovative non-invasive technology used for adenomyosis. Gonadotropin-releasing hormone agonist (GnRH-a) is a hormone commonly used for adenomyosis. We investigated and assessed the efficacy of HIFU combined with GnRH-a for adenomyosis. Methods: For this systematic review and meta-analysis, we searched Pubmed, Cochrane Library, Web of Science, Embase, CNKI, WanFang, and VIP databases for relevant articles published in Chinese or English that compared HIFU combined with GnRH-a vs. HIFU alone in patients with adenomyosis. The last literature search was completed on January 31, 2021. Two reviewers independently assessed study eligibility and assessed risk of bias. Another two reviewers extracted the data. The RevMan5.3 software was used for the data analysis. Changes in volume of the uterine and adenomyotic lesion were defined as the primary outcomes. The secondary outcomes were visual analog scale (VAS) scores for dysmenorrhea, menstrual volume scores, serum CA125 levels, and recurrence rate. This study is registered with PROSPERO (CRD42021234301). Results: Three hundred and ninety potentially relevant articles were screened. Nine studies with data for 766 patients were finally included. Compared with the HIFU alone group, the HIFU combined with GnRH-a group had a higher rate of uterine volume reduction (MD 7.51, 95% CI 5.84-9.17, p < 0.00001), smaller adenomyotic lesion volume (MD 4.11, 95% CI 2.93-5.30, p < 0.00001), lower VAS score for dysmenorrhea (MD 1.27, 95% CI 0.54-2.01, p = 0.0007) and menstrual volume score (MD 0.88, 95% CI 0.73-1.04, p < 0.00001), and lower CA125 level (SMD 0.31, 95% CI 0.05-0.56, p = 0.02) after the procedure. The recurrence rate in the HIFU combined with GnRH-a group was lower than that in the HIFU alone group (RR 0.28, 95% CI 0.10-0.82, p = 0.02). Conclusions: Compared with HIFU treatment alone, HIFU combined with GnRH-a for the treatment of adenomyosis has greater efficacy in decreasing the volumes of the uterine and adenomyotic lesions and alleviating symptoms. However, since the number of the included studies was too small and most of them were written in Chinese, this conclusion needs to be referenced with caution. And the long-term evidence of its efficacy is still insufficient. Systematic Review Registration : https://www.crd.york.ac.uk/prospero/ identifier [CRD42021234].; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Pang, Mei, Fan, Zhao, Li and Wen.)

Panjrath, Y. and V. N. Pathak (2022). "A SYSTEMATIC REVIEW ON THE IMPACT OF SURYA NAMASKAR AND LOVING KINDNESS MEDITATION IN TREATING SOCIAL BODY ANXIETY AND BODY DISSATISFACTION IN WOMEN WITH POLYCYSTIC OVARIAN SYNDROME." Journal of Pharmaceutical Negative Results 13: 10146-10151.
	PCOS, or polycystic ovary syndrome, is not a disease but rather a syndrome. Polycystic ovary syndrome and anxiety are on the rise in India's population. Given that PCOS is a psychosomatic condition, it necessitates both psychological and physiological care. Meditation and the yoga posture known as Suryanamaskar have been shown to alleviate and control the anxiety and PCOS symptoms that plague so many women. increases one's happiness and well-being in the long run. Aim(s): The goal of this research is to comprehensively evaluate the efficacy of Surya namaskar and meditation for the treatment of PCOS and anxiety. Method(s): It includes several research papers published between 2014 and 2021. Empirical studies of Surya namaskar and meditation, as well as the efficacy outcomes achieved via practice, were included as eligibility criteria. Tableau was used to graphically display the number of reviews, PCOS health outcomes, overcome with anxiety and intervention effects. About 24 research publications were carefully examined, and 12 were deemed to be the most pertinent for evaluation. Result(s): This map encompasses several studies, with Suryanamaskar and meditation was used for treating PCOS and anxiety being the key word that retrieved the highest number of results. Randomized controlled trials (RCTs), non-randomized controlled trials, and uncontrolled investigations were among the studies that were found. Various meditation and Surya namaskar practices were assessed in various situations. The bulk of studies on Surya namaskar and meditation practice showed positive results and a positive potential. Conclusion(s): Overall, the evidence suggests that Daily Suryanamaskar practice for 30 minutes with meditation helps management of anxiety and polycystic ovarian syndrome.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Panunzio, A., et al. (2022). "Botulinum Toxin-A Injection in Chronic Pelvic Pain Syndrome Treatment: A Systematic Review and Pooled Meta-Analysis." Toxins 14(1).
	Introduction: Pain management of patients with chronic pelvic pain syndrome (CPPS) is challenging, because pain is often refractory to conventional treatments. Botulinum toxin A (BTX-A) may represent a promising therapeutic strategy for these patients. The aim of this systematic review was to investigate the role of BTX-A in CPPS treatment.; Methods: We reviewed the literature for prospective studies evaluating the use of BTX-A in the treatment of CPPS. A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed from English language articles published between January 2000 and October 2021. The primary outcome was to evaluate pain improvement in CPPS after BTX-A treatment. Pooled meta-analysis of the included studies, considering the effect of BTX-A on pain evaluated at last available follow-up compared to baseline values, was performed together with meta-regression analysis.; Results: After screening 1001 records, 18 full-text manuscripts were selected, comprising 13 randomized clinical trials and five comparative studies. They covered overall 896 patients of both sexes and several subtype of CPPS (interstitial cystitis/bladder pain syndrome, chronic prostatitis/prostate pain syndrome, chronic scrotal pain, gynecological pelvic pain, myofascial pelvic pain). The clinical and methodological heterogeneity of studies included makes it difficult to do an overall estimation of the real effect of BTX-A on pain and other functional outcomes of various CPPS subtypes. However, considering pooled meta-analysis results, a benefit in pain relief was showed for BTX-A-treated patients both in the overall studies populations and in the overall cohorts of patients with CPP due to bladder, prostate, and gynecological origin.; Conclusions: BTX-A could be an efficacious treatment for some specific CPPS subtypes. Higher level studies are needed to assess the efficacy and safety of BTX-A and provide objective indications for its use in CPPS management.

Panyawongudom, N., et al. (2023). "Number of vaginal lactobacilli in postmenopausal women with vaginal atrophy before and after treatment with erbium-YAG laser: a randomized sham-controlled trial." BMC Women's Health 23(1): 513.
	Primary Objective: To evaluate the effect of erbium-YAG laser on the number of vaginal lactobacilli in postmenopausal women.; Secondary Objectives: To evaluate the effect of erbium-YAG laser on vaginal atrophy symptoms and vaginal pH in postmenopausal women.; Materials and Methods: A total of 44 postmenopausal women who met the inclusion criteria were randomized in the laser group (n = 22) and sham group (n = 22). Vaginal lactobacilli grading, vaginal pH, vaginal atrophy score, and vaginal atrophy symptoms were assessed before and after treatment with erbium-YAG laser for two consecutive times, with a four-week interval; the results were compared with the effects of the sham procedure. Any adverse events after the treatment were recorded.; Results: A total of 44 women were included, and five were lost to follow-up. Compared with sham procedure, vaginal lactobacilli grading improved in the laser group (5/20 in the laser group and 1/19 in the sham group). However, the improvement did not reach statistical significance (adjusted odds ratio = 5.32, 95% CI = 0.5-56.21). Vaginal atrophy symptoms measured by the visual analog scale (VAS) and vaginal pH were improved in both groups without a statistically significant difference between the two groups. Vaginal "dryness" VAS and vaginal atrophy score after treatment were significantly lowered in the laser group compared with the sham group.; Conclusions: This study showed an improvement in vaginal lactobacilli grading after vaginal laser treatment. However, the difference in vaginal lactobacilli grading after treatment in both groups was not statistically significant. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Panza, J. and W. S. Reynolds (2019). "Hormone Replacement for Pelvic Floor Disorders." Current Bladder Dysfunction Reports 14(4): 266-271.
	Purpose of Review: The purpose of this review article is to summarize the recent literature regarding the effect of hormone replacement therapy on pelvic floor disorders and its role as a preventative or treatment option. Recent Findings: The recent evidence describing the effect of hormone replacement therapy on pelvic floor disorders is mainly limited to cohort studies, systematic reviews, and secondary analysis of randomized controlled trials such as the Women's Health Initiative and Nurses' Health Study. There are few quality randomized controlled trials, especially within the last 5 years on this topic. The data that does exist does not show hormone therapy to be beneficial in the treatment or prevention of pelvic floor disorders. In fact, it may worsen urinary and fecal incontinence when given systemically. The exception to this is the local application of vagina estrogen, where it may be of some benefit in the treatment of urinary incontinence. Local application has been shown to be beneficial when treating genitourinary syndrome of menopause and in the prevention of recurrent urinary tract infections. Summary: There is a paucity of quality data regarding the secondary effects and use of hormone replacement as a treatment for pelvic floor disorders. Given the lack of studies, limited efficacy, and possible side effects, it should not be offered as first-line or single treatment for pelvic floor disorders such as urinary or fecal incontinence and pelvic organ prolapse. It may be used as a treatment for genitourinary syndrome of menopause and for prevention of urinary tract infections when placed locally in the vagina.Copyright © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Paoletti, X., et al. (2020). "Assessment of Progression-Free Survival as a Surrogate End Point of Overall Survival in First-Line Treatment of Ovarian Cancer: A Systematic Review and Meta-analysis." JAMA Network Open 3(1): e1918939.
	Importance: The Gynecologic Cancer InterGroup (GCIG) recommended that progression-free survival (PFS) can serve as a primary end point instead of overall survival (OS) in advanced ovarian cancer. Evidence is lacking for the validity of PFS as a surrogate marker of OS in the modern era of different treatment types.; Objective: To evaluate whether PFS is a surrogate end point for OS in patients with advanced ovarian cancer.; Data Sources: In September 2016, a comprehensive search of publications in MEDLINE was conducted for randomized clinical trials of systematic treatment in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer. The GCIG groups were also queried for potentially completed but unpublished trials.; Study Selection: Studies with a minimum sample size of 60 patients published since 2001 with PFS and OS rates available were eligible. Investigational treatments considered included initial, maintenance, and intensification therapy consisting of agents delivered at a higher dose and/or frequency compared with that in the control arm.; Data Extraction and Synthesis: Using the meta-analytic approach on randomized clinical trials published from January 1, 2001, through September 25, 2016, correlations between PFS and OS at the individual level were estimated using the Kendall τ model; between-treatment effects on PFS and OS at the trial level were estimated using the Plackett copula bivariate (R2) model. Criteria for PFS surrogacy required R2 ≥ 0.80 at the trial level. Analysis was performed from January 7 through March 20, 2019.; Main Outcomes and Measures: Overall survival and PFS based on measurement of cancer antigen 125 levels confirmed by radiological examination results or by combined GCIG criteria.; Results: In this meta-analysis of 17 unique randomized trials of standard (n = 7), intensification (n = 5), and maintenance (n = 5) chemotherapies or targeted treatments with data from 11 029 unique patients (median age, 58 years [range, 18-88 years]), a high correlation was found between PFS and OS at the individual level (τ = 0.724; 95% CI, 0.717-0.732), but a low correlation was found at the trial level (R2 = 0.24; 95% CI, 0-0.59). Subgroup analyses led to similar results. In the external validation, 14 of the 16 hazard ratios for OS in the published reports fell within the 95% prediction interval from PFS.; Conclusions and Relevance: This large meta-analysis of individual patient data did not establish PFS as a surrogate end point for OS in first-line treatment of advanced ovarian cancer, but the analysis was limited by the narrow range of treatment effects observed or by poststudy treatment. These results suggest that if PFS is chosen as a primary end point, OS must be measured as a secondary end point.

Paolo, S., et al. (2023). "Thromboembolic and bleeding risk in cancer patients undergoing treatment with bevacizumab: a systematic review and meta-analysis."
	
Papaetis Georgios, S. and A. Kyriacou (2022). "GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons." Advances in clinical and experimental medicine : official organ Wroclaw Medical University 31(11): 1265-1274.
	Polycystic ovary syndrome (PCOS) is a disorder that involves several organ systems and cellular pathways. It is strongly influenced by environmental and epigenetic factors. The principal goal of all therapeutic approaches to individuals with reproductive abnormalities is the treatment of subfertility or the regulation of menstruation when pregnancy is not desired. Obesity is closely related to insulin resistance (IR) and subsequent hyperinsulinemia, which aggravate hyperandrogenism and impair early follicle development. Weight loss is of vital importance for overweight/obese individuals with anovulatory infertility. The GLP-1R agonists have achieved remarkable weight reduction and abdominal fat loss in patients with type 2 diabetes (T2D), as well as in overweight/obese individuals and individuals with prediabetes. They have also been shown to promote lower fasting insulin levels and insulin resistance markers. These beneficial effects have been suggested to be particularly helpful in women with PCOS, while their possible role in the hypothalamic-pituitary-gonadal axis is under intense research. This review analyzes the current evidence for GLP-1R agonists, focusing on their effects on ovarian morphology, menstrual dysfunction and fertility outcomes. It also discusses their future role in achieving targeted therapeutic approaches.

Papageorgiou, D., et al. (2022). "Fertility outcomes after treatment with intraperitoneal chemotherapy." Journal of Obstetrics and Gynaecology 42(6): 1626-1634.
	Intraperitoneal chemotherapy (IPC) administration has been added to the therapeutic protocols of cancers, confined to the abdominal cavity. Since, a survival benefit in patients treated with adjuvant IPC has been demonstrated, fertility questions are raised in these patients. A comprehensive search of the English literature of PubMed/MEDLINE, EmBase and Google Scholar databases was conducted, from their inception until April 2021, following the MOOSE guidelines. Twelve out of 473 studies were included in the final review and analysis. After treatment with IPC for peritoneal carcinomatosis, 19 women, who underwent fertility-sparing surgery, with 20 successful pregnancies were reported. The mean interval time between IPC and pregnancy was 38.4 months (range 9-168 months). In 16 cases, conception was spontaneous, three required in vitro fertilisation, whereas one pregnancy was achieved through intrauterine insemination. Mean disease-free survival was 76 months (range 24-177 months). Childbearing is a feasible approach in selected patients, after treatment with IPC. When future pregnancy is desirable, a multidisciplinary team of surgeons, gynaecologists, oncologists and reproductive specialists is required, to inform the patient thoroughly about the fertility preservation alternatives, without endangering patient's survival.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Papakonstantinou, E., et al. (2021). "DNA Methylation in Epithelial Ovarian Cancer: Current Data and Future Perspectives." Current molecular pharmacology 14(6): 1013-1027.
	Ovarian cancer is an aggressive disease, and only a few cases are diagnosed at early stages due to the absence of symptoms. Τhe majority of malignant ovarian tumors (>90%) are of epithelial origin and are subdivided into five histological sub types according to different molecular pathogenesis and clinical behavior. High-grade serous ovarian cancer is the most common subtype (70%). However, the different histotypes of ovarian cancer should be viewed as separate diseases both clinically and in biomarker studies. At present, surgical debulking and platinum/taxane - based chemotherapy is the standard of care for epithelial ovarian cancer. Most patients show an initial response to this therapeutic approach, but the majority of them experience disease recurrence at which point cure is no longer possible, due to acquired resistance in those chemotherapeutic regimens. Nevertheless, the current treatment model is still a "one-sizefits- all" approach. Epigenetic modifications represent heritable modifications in gene expression without alteration of the DNA sequence. DNA methylation is the best-studied epigenetic mechanism, and in epithelial ovarian cancer, the methylenome is widely altered. In addition, patterns of DNA methylation may represent potential diagnostic and prognostic markers as well as markers predictive of chemoresistance and potential therapeutic targets. This article systematically reviews the complex area of DNA methylation in ovarian carcinoma and summarizes the current implications and future perspectives of its use as a screening, diagnostic, prognostic and predictive tool as well as in personalized cancer therapy. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Papanikolaou, D. T., et al. (2023). "Pelvic floor muscle training: Novel versus traditional remote rehabilitation methods. A systematic review and meta-analysis on their effectiveness for women with urinary incontinence." Neurourology and Urodynamics 42(4): 856-874.
	Objective: To investigate the effectiveness of supervised remote rehabilitation programs comprising novel methods of pelvic floor muscle (PFM) training for women with urinary incontinence (UI). Design(s): A systematic review and meta-analysis including randomized controlled trials (RCTs), involving novel supervised PFM rehabilitation programs as intervention groups (e.g., mobile applications programs, web-based programs, vaginal devices) versus more traditional PFM exercise groups (acting as control); both sets of groups being offered remotely. Method(s): Data have been searched and retrieved from the electronic databases of Medline, PUBMED, and PEDro using relevant key words and MeSH terms. All included study data were handled as reported in the Cochrane Handbook for Systematic Reviews of Interventions and the evaluation of their quality was undertaken utilizing the Cochrane risk-of-bias tool 2 (RoB2) for RCTs. The included RCTs, involved adult women with stress UI (SUI) or mixed urinary incontinence, where SUI were the most predominant symptoms. Exclusion criteria involved pregnant women or up to 6-month postpartum, systemic diseases and malignancies, major gynecological surgeries or gynecological problems, neurological dysfunction or mental impairments. The searched outcomes included subjective and objective improvements of SUI and exercise adherence in PFM exercises. Meta-analysis was conducted and included studies pulled by the same outcome measure. Result(s): The systematic review included 8 RCTs with 977 participants. Novel rehabilitation programs included mobile applications (1 study), web-based programs (1 study) and vaginal devices (6 studies) versus more traditional remote PFM training, involving home-based PFM exercise programs (8 studies). Estimated quality with Cochrane's RoB2, presented the 80% of the included studies as "some concerns" and the 20% as "high risk." Meta-analysis included 3 studies with no heterogeneity (I2 = 0) across them. Weak-evidenced results presented home PFM training equally effective with novel PFM training methods (mean difference: 0.13, 95% confidence interval: -0.47, 0.73), with small total effect size (0.43). Conclusion(s): Novel PFM rehabilitation programs presented as effective (but not superior) to traditional ones in women with SUI, both offered remotely. However, individual parameters of novel remote rehabilitation including supervision by the health professional, remains in question and larger RCTs are required. Connection between devices and applications in combination with real-time synchronous communication between patient and clinician during treatment is challenged for further research across novel rehabilitation programs.Copyright © 2023 Wiley Periodicals LLC.

Papanikolaou, E., et al. (2023). "Guided Imagery and Music in the Treatment for Breast and Gynecologic Cancer: An RCT Pilot." Journal of music therapy 60(4): 410-434.
	The primary aim of this randomized controlled trial pilot was to investigate the potential effectiveness of the music psychotherapy method, Guided Imagery and Music (GIM), to assist female patients who are undergoing chemotherapy treatment for breast or gynecologic cancer. A secondary aim was to suggest performance improvements regarding the protocol and the resources required to undertake a future larger scale study. The researchers randomized participants (n = 20) into two groups: Intervention group (n = 10) and Control group (n = 10). The Intervention group received a series of six individual, short GIM sessions whereas the Control group received two verbal counseling sessions that took place at Week 1 and at Week 6 of treatment. All participants in the study completed the Profile of Mood States (POMS-Brief); Cancer Fatigue Scale (CFS); and Herth Hope Index (HHI) before the beginning of Week 1 and again after Week 6 or, in the case of the Intervention group, after the last GIM session. All participants also completed two Visual Analogue Scales (VAS-Hope; VAS-Fatigue) weekly or after each session throughout the duration of the trial. The results of the Intervention group receiving GIM showed medium pre-post effect sizes for the CFS, HHI, and POMS questionnaires, and significant positive changes for the VAS-H and VAS-F questionnaires. As seen from this initial data outcome, a brief series of GIM sessions shows promise to be beneficial for increasing hope, decreasing fatigue, and mitigating distressed mood for female patients undergoing treatment for breast or gynecologic cancer. (© The Author(s) 2023. Published by Oxford University Press on behalf of American Music Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Papanikolaou, E., et al. (2023). "Endometrial scratching during hysteroscopy in women undergoing in vitro fertilization: a systematic review and meta-analysis." Frontiers in surgery 10: 1225111.
	Objective: Endometrial scratching (ES) during hysteroscopy before embryotransfer (ET) remains doubtable on whether it benefits the reproductive outcomes. The optimal technique is not clear and repeated implantation failure as a challenging field in in vitro fertilization (IVF) seems to be the springboard for clinicians to test its effectiveness.; Methods: Medline, PMC, ScienceDirect, Scopus, CENTRAL, Google Scholar were searched from their inception up to April 2023 for studies to evaluate the effectiveness of adding endometrial scratching during hysteroscopy before ET.; Results: The initial search yielded 959 references, while 12 eligible studies were included in the analyses, involving 2,213 patients. We found that hysteroscopy and concurrent ES before ET resulted in a statistically significant improvement in clinical pregnancy rate (CPR) [RR = 1.50, (95% CI 1.30-1.74), p < 0.0001] and live birth rate (LBR) [RR = 1.67, (95% CI 1.30-2.15), p < 0.0001] with no statistically significant difference on miscarriage rate [RR = 0.80 (95% CI 0.52-1.22), p = 0.30].; Conclusion: Our meta-analysis suggests that hysteroscopy with concurrent ES may be offered in IVF before ET as a potentially improving manipulation. Future randomized trials comparing different patient groups would also provide more precise data on that issue, to clarify specific criteria in the selection of patients.; Systematic Review Registration: PROSPERO (CRD42023414117).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Papanikolaou, Peitsidis, Tsakiridis, Michos, Skalias, Patoulias, Poutoglidis, Mamopoulos, Athanasiadis, Grimpizis and Najdecki.)

Pareek, V., et al. (2021). "Presentation Time: 11: 40 AM: a Phase III Randomised Trial of Trans-Abdominal Ultrasound in Improving Application Quality and Dosimetry of Intra-Cavitary Brachytherapy in Locally Advanced Cervical Cancer." Brachytherapy 20(3): S31‐.
	Introduction: Intra‐cavitary brachytherapy (ICB) remains an integral part of radiotherapy treatment in cervical cancer. Two‐dimensional X ray point‐based planning remains common and blind insertion leads to uterine perforations and higher toxicity. We conducted a randomised controlled trial of using trans‐abdominal ultrasound in performing ICB to reduce perforation and organ at risk doses. Patient and Methods: The present study is a phase III open label randomised controlled trial of ultrasound guided ICB conducted on invasive cervical cancer patients. Patients were randomised by a simple computer‐generated randomization chart into Arm A (No Ultrasound guidance) and Arm B (ICB with ultrasound guidance). The uterine perforation rates, tandem length change rates, bladder doses, rectal dose and procedure times were compared. Fischer exact test was used to compare the arms and p value <0.05 considered significant. Results: A total of 160 patients were randomised. With US assistance, the uterine perforation rate was 1.25% (n = 1). In the non‐US assistance arm the perforation rate was 12.5% (n = 10) (p = 0.005). Mean time to complete the entire procedure was significantly shortened from 26 min to 19 min favouring the US arm (p = 0.001). Dosimetric assessment between the two groups showed significant decrease in dose received by the various organs at risk with US assistance. Conclusion: The present study confirms significant improvement in application quality as well as dosimetry with reduction in procedure time. Trans‐Abdominal US should be routinely used for ICB procedures, particularly in resource limited settings.

Pareek, V., et al. (2021). "A phase III randomised trial of trans-abdominal ultrasound in improving application quality and dosimetry of intra-cavitary brachytherapy in locally advanced cervical cancer." Gynecologic Oncology 160(2): 375-378.
	INTRODUCTION: Intra-cavitary brachytherapy (ICB) remains an integral part of radiotherapy treatment in cervical cancer. Two-dimensional X ray point-based planning remains common and blind insertion leads to uterine perforations and higher toxicity. We conducted a randomised controlled trial of using trans-abdominal ultrasound in performing ICB to reduce perforation and organ at risk doses. PATIENT AND METHODS: The present study is a phase III open label randomised controlled trial of ultrasound guided ICB conducted on invasive cervical cancer patients. Patients were randomised by a simple computer-generated randomization chart into Arm A (No Ultrasound guidance) and Arm B (ICB with ultrasound guidance). The uterine perforation rates, tandem length change rates, bladder doses, rectal dose and procedure times were compared. Fischer exact test was used to compare the arms and p value <0.05 considered significant. RESULTS: A total of 160 patients were randomised. With US assistance, the uterine perforation rate was 1.25% (n = 1). In the non-US assistance arm the perforation rate was 12.5% (n = 10) (p = 0.005). Mean time to complete the entire procedure was significantly shortened from 26 min to 19 min favouring the US arm (p = 0.001). Dosimetric assessment between the two groups showed significant decrease in dose received by the various organs at risk with US assistance. CONCLUSION: The present study confirms significant improvement in application quality as well as dosimetry with reduction in procedure time. Trans-Abdominal US should be routinely used for ICB procedures, particularly in resource limited settings.

Parenti, M., et al. (2023). "Botulinum toxin injection in vulva and vagina. Evidence from a literature systematic review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 291: 178-189.
	Introduction: Botulinum toxin (BoNT) administration has been proposed in the gynecologic field for pelvic, vulvar and vaginal disorders. On this regard, we aimed assessing the therapeutic effectiveness and safety of BoNT usage in the treatment of vaginal, vulvar and pelvic pain disorders.; Methods: We searched for all the original articles without date restriction until 31.12.2021. We included all the original articles which administered botulinum toxin in the vulva or vagina of women suffering from vaginismus, dyspareunia, and chronic pelvic pain. Only English language studies and those performed in humans were eligible. We excluded all case reports and pilot study from the qualitative analysis, although we accurately evaluated them. 22 original studies were finally included in the systematic review.; Results: Botulinum toxin injection was found to be effective in improving vulvar and vaginal dyspareunia, vaginismus, and chronic pelvic pain. No irreversible side effects were detected. Major side effects reported were transient urinary or fecal incontinence, constipation and rectal pain. The risk of bias assessment proved original articles to be of medium quality. No metanalysis could have been performed since lack of congruency in the definition of pathology and methods of botulinum toxin administration.; Conclusion: Data extraction pointed out different endpoints and different methods of analysis. Studies focus on different types of participants and use various techniques and timing. According to the best evidence available, different techniques provide evidence about positive outcomes, with the need for a standardized protocol.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Parhar, P., et al. (2023). "Comparing clomiphene citrate/ flexible GnRH antagonist vs ultrashort flare GnRH agonist protocols for controlled ovarian stimulation in poor ovarian reserve patients." Human Reproduction 38(Supplement 1): i506.
	Study question: How do Clomiphene citrate (CC)/ flexible GnRH antagonist and ultrashort flare GnRH agonist protocols compare in poor ovarian reserve patients (POSEIDON groups 3 & 4)? Summary answer: In poor ovarian reserve patients, irrespective of age, use of CC / flexible antagonist vs ultrashort flare protocol significantly reduces gonadotrophin consumption and stimulation duration. What is known already: Poor responders constitute 47% of ART patients and up to 65% of these have diminished ovarian reserve. Despite the various treatment options available, lack of good quality evidence to enable recommendation of a particular protocol or adjuvant continues to pose a challenge to their effective management. The need for multiple stimulations for pooling up embryos also makes effective cost of treatment an added concern in them. Study design, size, duration: An open label, multi centric, randomized controlled study was conducted over a period of 1 year recruiting 116 women having AMH >1.2ng/dl and antral follicle count (AFC) >5 who were further analysed in POSEIDON 3 and 4 subgroups. Patients were randomized to 1 of 2 groups for controlled ovarian stimulation. Those with severe endometriosis, adenomyosis, autoimmune or metabolic disorders, sustained hyperprolactinaemia, congenital uterine malformations and with male partners having severe oligoasthenoteratozoospermia were excluded. Participants/materials, setting, methods: Group A (55 women) received CC 100mg from D1-D5 with 300 IU human menopausal gonadotrophin (hMG) in a flexible GnRH antagonist protocol. Group B (61 women) underwent ultrashort flare protocol. 1mg leuprolide was administered from D1-D4 and 300 IU hMG given D2 onwards followed by flexible GnRH antagonist administration. Dual trigger with triptorelin and recombinant hCG was administered 35-36 hours before oocyte retrieval. Embryos cultured till D5 were vitrified for transfer at a later stage. Main results and the role of chance: The two groups were well matched for baseline characteristics like age, BMI, AMH, duration of infertility, D2 AFC, estradiol and FSH levels. The mean total gonadotrophin consumption (3387.29 + 1082.5 vs 4407 + 1224.2, p value >0.01) and the duration of stimulation (10.71 + 2.52 vs 11.95 + 2.43, p value >0.01) were significantly lower in group A vs group B. The primary outcomes of median number of oocytes retrieved (4 vs 4, p value- 0.71) , M2 rate (3 vs 3, p value-0.91), fertilisation rate were similar in the two groups. The secondary outcomes of oocyte retrieval rate (103.05 + 42.97 vs 97.14+42.96, p value- 0.63), FORT (0.81 +0.68 vs 0.96+0.48, p value- 0.37) FOI (0.91+0.55 vs 0.92+ 0.54, p value 0.92), top quality embryo rate (0.53+1.1 vs 0.41+0.84, p value 0.61), cycle cancellation rate (26.22% vs 29.09%), implantation rate (23.63% vs 24.59%) and clinical pregnancy rate (21.31% vs 20%) were also similar in group A vs B respectively. A subgroup analysis of POSEIDON 3 versus POSEIDON 4 patients revealed similar outcomes with both the protocols in the two groups. Limitations, reasons for caution: Small sample size of the cases limits the current statistical power of the study. Wider implications of the findings: CC /flexible GnRH antagonist protocol is an effective alternative to ultrashort flare protocol in patients with poor ovarian reserve irrespective of their age. The lower gonadotrophin dosage required and shorter duration of stimulation observed make it a viable option in patients who might need multiple stimulations for pooling up embryos.

Paris Assistance Publique - Hôpitaux, d. (2021). Improvement of Live Babies Rates After ICSI, Using cpFT.
	No Results Available Drug: Cyclic peptide Fertiline Live birth rate after the first embryo transfer|Level of Metaphase II oocytes|Quality of the embryonic culture|Evaluation of the kinetics of embryonic development when possible.|Embryonic quality at the blastocyst stage|Quality of the embryos after vitrification|Implantation rate with positive Beta hCG after transfer|Clinical pregnancy rates with cardiac activity|The rate of miscarriages per pregnancy|rate of abnormality on morphological ultrasounds|rate of neonatal abnormality|children's development Female Phase 3 366 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment P170706J August 26, 2024

Park, H.-R., et al. (2019). "Cangfu daotan decoction for polycystic ovary syndrome: A protocol of systematic review and meta-analysis." Medicine 98(39): e17321.
	Backgrounds: Polycystic ovary syndrome (PCOS) is common endocrine disorder in women and can lead to serious social burdens associated with various reproductive and metabolic abnormalities. Existing therapy is controversial in its effectiveness including side effects. In traditional Korean Medicine, Cangfu Daotan Decoction (CDD), also known as Changbudodam-tang, is used for PCOS patients who are in the type of stagnation of phlegm and dampness. In this study, we aimed to evaluate the efficacy and safety of CDD for PCOS as alternative treatment.; Methods: Two researchers will search the following databases from their inception to February 2019 for relevant randomized controlled trials (RCTs): The Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and 5 Korean medical databases (Korean Studies Information Service System, KoreaMed, DBPIA, Oriental Medicine Advanced Searching Integrated System, and Research Information Service System). The primary outcome will be the scales that assessed drug efficacy including total response rate, sex hormone level (LH, FSH, Testosterone, LH/FSH ratio), BMI, ovulation rate, and pregnancy rate. Adverse events will be assessed as the secondary outcome. Study selection, data extraction, and assessment of risk of bias will be conducted by 2 researchers independently. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software.; Results and Conclusion: This review will provide the latest knowledge and evidence on the efficacy and safety of CDD for PCOS women through the analysis of various evaluation scales.; Ethics and Dissemination: This systematic review does not require ethical approval and will be published in a peer-reviewed journal.; Prospero Registration Number: CRD42019134270.

Park, J., et al. (2022). "Second-line olaparib maintenance therapy is associated with poor response to subsequent chemotherapy in BRCA1/2-mutated epithelial ovarian cancer: A multicentre retrospective study." Gynecologic Oncology 165(1): 97-104.
	Introduction: With expanded use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi), there is a potential impact of PARPi resistance on platinum resistance. A post-hoc analysis of SOLO2 demonstrated a reduction in response to subsequent platinum-based therapy among patients who received prior olaparib but not placebo. The present multicentre, retrospective, observational study was conducted to determine the effects of olaparib on subsequent therapy for recurrent epithelial ovarian cancer (EOC).; Materials and Methods: Data on EOC patients with BRCA1/2-mutated tumours who received second-line platinum-based chemotherapy between January 2012 and June 2020, at three South Korean institutions (n = 197) were collected. Patients who received olaparib as maintenance therapy after second-line chemotherapy were assigned to the olaparib group (n = 105), and subjects who did not receive olaparib maintenance therapy were assigned to the control group (n = 92). The primary endpoint was time intervals from the date of second disease progression (PFS1) to the date of third disease progression (PFS2), expressed as PFS2 - PFS1.; Results: As expected, PFS1 in the olaparib group was longer than the control group. However, PFS2 - PFS1 in the olaparib group was significantly shorter than that of the control group (median 7.9 vs. 13.6 m; p = 0.0005). Even when the third-line PARPi maintenance (cross-over) patients were excluded from the control group, the response to subsequent therapy in the olaparib group remained poor (median 7.7 vs. 11.5; p = 0.0422).; Discussions: Patients with platinum-sensitive BRCA1/2 mutated tumours who progressed during olaparib maintenance after second-line chemotherapy were less likely to respond to third-line chemotherapy compared to controls who did not receive olaparib, suggesting that resistance to olaparib may contribute to chemotherapy resistance.; Competing Interests: Declaration of Competing Interest Jung-Yun Lee reported institutional financial interest (clinical trials/ contracted research) from AstraZeneca, Beigene, Bergenbio, Clovis Oncology, Eutilex, Immunogen, Janssen, Merck, MSD, Synthon, and TAKEDA; advisory board of AstraZeneca, Eisai, Merck, MSD, and TAKEDA. Jae-Weon Kim reported personal fee from Astra Zeneca, CMIC, and Janssen; advisory board of Boryung, GSK Korea, LG Pharma, MSD Korea, Takeda Korea, and Vifor Pharma. Byung-Gie Kim reported research fund from AstraZeneca, Cellid, and Utilex; advisory board of AstraZeneca, MSD, Esai, and Cellid. Michael A. Bookman reported participation on a Data Safety Monitoring Board or Advisory Board of Immunogen, AbbVie, Genetech-Roche, and Merk (Sharp & Dohme). All remaining authors declare no conflict of interest. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Park, J. Y., et al. (2023). "FloSeal for preventing symptomatic lymphocele after pelvic and/or para-aortic lymphadenectomy in gynecological cancers: a randomized controlled trial." European Journal of Gynaecological Oncology 44(5): 67-74.
	To evaluate the role of FloSeal for preventing symptomatic lymphocele following pelvic and/or para-aortic lymphadenectomy in patients with gynecological cancers. Between October 2014 and April 2015, 40 patients with gynecological cancers planned for surgical management were randomly placed into FloSeal and non-FloSeal groups in a 1:1 ratio. Lymphocele incidence was evaluated using intravenous contrast-enhanced, abdominopelvic computed tomography 3-6 months after surgery. The quality of life questionnaire was completed by patients at 1, 3 and 6 months after surgery. The incidence of symptomatic lymphocele was compared using a chi-square test. All patients underwent bilateral pelvic lymph node dissection, and eight patients in each group (40% vs. 44.4%, p > 0.999) underwent para-aortic lymph node dissection. The mean number of total, right pelvic, left pelvic and para-aortic lymph nodes retrieved was similar between the groups. One patient (1/20, 5%) in the FloSeal group and three (3/18, 16.7%) in the non-FloSeal group developed lymphoceles (p = 0.328). The incidence of symptomatic lymphocele was 0% and 11% (2/18) in the FloSeal and non-FloSeal groups (p = 0.218), respectively. The mean time interval to drain removal (4.8 +/- 2.0 days vs. 5.3 +/- 2.2 days, p = 0.400) was shorter and the mean drain volume (1656 +/- 1362 mL vs. 2022 +/- 2301 mL, p = 0.550) was smaller in FloSeal group. The use of FloSeal after pelvic and/or para-aortic lymphadenectomy in patients with gynecological cancers may be effective for preventing symptomatic lymphocele. Clinical Trial registration: NCT01679483.Copyright © 2023 The Author(s). Published by MRE Press.

Park, K. H., et al. (2024). "Effects of an urban forest healing program on cancer-related fatigue in cancer survivors." Supportive Care in Cancer 32(1): 4.
	Purpose: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. Background(s): Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. Method(s): A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (>= 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. Result(s): Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. Conclusion(s): This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. Trial registration number: KCT0008447 (Date of registration: May 19, 2023).Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Park, M., et al. (2022). "The efficacy of gonadotropin-releasing hormone agonist treatment before hysteroscopic myomectomy for large-sized submucosal leiomyoma." Medicine 101(31): e29726.
	To evaluate the efficacy and safety of a gonadotropin-releasing hormone (GnRH) agonist for treating large-sized submucosal leiomyoma before hysteroscopic myomectomy. The data were retrospectively collected from patients who underwent a hysteroscopic myomectomy for a submucosal leiomyoma >3.5 cm in size from January 2009 to December 2018. The patients were divided into the GnRH group and the control group according to whether they were pretreated before surgery. A total of 61 patients were included in the study, 31 in the GnRH agonist group and 30 in the control group. At diagnosis, the maximum leiomyoma diameter was similar between the 2 groups (4.67 ± 0.6 cm in the GnRH agonist group vs 3.82 ± 0.6 cm in the control group, P = .061). After pretreatment with the GnRH agonist, the maximum diameter was significantly smaller in the GnRH agonist group compared to the control group (3.82 ± 0.6 vs 4.33 ± 0.8 cm, respectively, P = .004). The leiomyoma volume in the GnRH agonist group decreased by 55.6%, from 41.68 ± 15.7 to 23.19 ± 10.4 cm3, which led to significant differences in leiomyoma volume between the 2 groups (23.19 ± 10.4 cm3 in the GnRH agonist group vs 33.22 ± 24.7 cm3 in the control group, P = .042). The GnRH agonist group showed a shorter operation time (37.7 vs 43.9 minutes, P = .040) and less uterine distention media was used (6800 vs 9373.3 mL, P = .037) compared to the control group. Postoperative complications such as estimated blood loss, remnant leiomyoma, and recurrence were similar between the 2 groups. Treatment with a GnRH agonist before hysteroscopic myomectomy for large submucosal leiomyoma might decrease the volume of the leiomyoma, reduce operation time, and the amount of uterine-distension media used without surgical complications.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Park, S.-H., et al. (2023). "Efficacy and Safety of MED-01 Probiotics on Vaginal Health: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial." Nutrients 15(2).
	Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 10 9 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.

Park, S. J., et al. (2021). "A randomized controlled trial of ovarian reserve preservation and hemostasis during ovarian cystectomy." Scientific Reports 11(1): 8495.
	The preservation of ovarian reserve during laparoendoscopic single-site (LESS) ovarian cystectomy is crucial for reproductive-age women. This study was a single-blinded, single-center, and randomized controlled trial to evaluate the effect of hemostatic agents on the preservation of ovarian reserve and hemostasis during LESS ovarian cystectomy. Patients with unilateral ovarian cyst were randomized to the hemostatic agent and coagulation groups according to the hemostasis method. Afterwards, the patients underwent LESS ovarian cystectomy, and hemostasis was performed after ovarian cyst excision according to the assigned hemostasis method. If hemostasis was not completed within 10 min. After discharge, the patients were followed until 3 months after surgery. We compared the hemoglobin, anti-Müllerian hormone (AMH) levels, and ovarian volumes before surgery, and 2 days, 1 week, and 3 months after surgery (3 M-POST), and the decline ratio between the two groups. The decline ratio of serum AMH levels was greater at 3 M-POST in the coagulation than in the hemostatic agent group (median intention-to-treat [ITT], - 36.7 vs. - 13.3%; per-protocol [PP], - 36.8 vs. - 13.3%; P < 0.05). Notably, the difference of the decline ratio of serum AMH levels was only shown in endometriosis patients (median; ITT, - 50.7 vs. - 14.4%; PP, - 50.7% vs. - 14.4%; P < 0.05), while there was no difference in non-endometriosis patients. In conclusion, Hemostatic agents may be non-inferior to bipolar coagulation for preserving ovarian reserve and hemostasis during LESS ovarian cystectomy, in particular, for endometriosis patients. (Trial registry: ClinicalTrials.gov Identifier NCT03374397).

Park, S. J., et al. (2021). "Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer: study protocol for a phase III, double-blind, randomized study."
	BACKGROUND: The second‐line chemotherapy using paclitaxel, carboplatin, and bevacizumab for treating platinum‐sensitive recurrent ovarian, fallopian or primary peritoneal cancer frequently cause chemotherapy‐induced peripheral neuropathy (CIPN), which is significantly associated with deterioration of quality of life. Despite the potential of some agents to prevent and treat CIPN, and there is still a lack of evidence of the effect. Although selenium has been suggested as an antioxidant candidate to prevent CIPN, there are insufficient data regarding its effect due to its low dose by oral administration. Thus, we hypothesized intravenous administration of high‐dose selenium (2,000 mug/day) at each cycle of the second‐line chemotherapy would prevent and reduce CIPN in patients with platinum‐sensitive recurrent ovarian, fallopian or primary peritoneal cancer. METHOD(S): This trial is an investigator‐initiated, phase III, double‐blinded, randomized controlled trial to evaluate the efficacy and safety of intravenous administration of high‐dose selenium (2,000 mug/day) for preventing CIPN in patients with platinum‐sensitive recurrent ovarian, fallopian or primary peritoneal cancer who receive paclitaxel, carboplatin, and bevacizumab. A total of 68 patients will be randomly assigned to the experimental and control groups at a 1:1 ratio. As the primary endpoint, the incidence rate of CIPN three months after six cycles of chemotherapy will be compared between the two groups according to the combined criteria of neuropathy using the World Health Organization‐CIPN criteria and Common Terminology Criteria for Adverse Events version 5.0. As secondary endpoints, we will compare adverse events, patient‐reported quality of life, and requirement of concomitant drugs for reducing CIPN between the two groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04201561.Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Park Soo, J., et al. (2022). "A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer." BMC Cancer 22(1): 28.
	Background: PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer.; Methods: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101.; Discussion: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer.; Trial Registration: ClinicalTrials.gov Identifier: NCT04678102 . (© 2021. The Author(s).)

Park Soo, J., et al. (2022). "Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol." BMC Cancer 22(1): 331.
	Background: The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer.; Methods: This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%.; Discussion: We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery.; Trial Registration: ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020. (© 2022. The Author(s).)

Park Soo, J., et al. (2020). "Reduction of cycles of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian or primary peritoneal cancer (ROCOCO): study protocol for a phase III randomized controlled trial." BMC Cancer 20(1): 385.
	Background: Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer.; Methods: This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years.; Discussion: We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable.; Trial Registration: This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).

Park Soo, J., et al. (2021). "Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer: study protocol for a phase III, double-blind, randomized study." Journal of Gynecologic Oncology 32(5): e73.
	Background: The second-line chemotherapy using paclitaxel, carboplatin, and bevacizumab for treating platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer frequently cause chemotherapy-induced peripheral neuropathy (CIPN), which is significantly associated with deterioration of quality of life. Despite the potential of some agents to prevent and treat CIPN, and there is still a lack of evidence of the effect. Although selenium has been suggested as an antioxidant candidate to prevent CIPN, there are insufficient data regarding its effect due to its low dose by oral administration. Thus, we hypothesized intravenous administration of high-dose selenium (2,000 μg/day) at each cycle of the second-line chemotherapy would prevent and reduce CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer.; Method: This trial is an investigator-initiated, phase III, double-blinded, randomized controlled trial to evaluate the efficacy and safety of intravenous administration of high-dose selenium (2,000 μg/day) for preventing CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer who receive paclitaxel, carboplatin, and bevacizumab. A total of 68 patients will be randomly assigned to the experimental and control groups at a 1:1 ratio. As the primary endpoint, the incidence rate of CIPN three months after six cycles of chemotherapy will be compared between the two groups according to the combined criteria of neuropathy using the World Health Organization-CIPN criteria and Common Terminology Criteria for Adverse Events version 5.0. As secondary endpoints, we will compare adverse events, patient-reported quality of life, and requirement of concomitant drugs for reducing CIPN between the two groups.; Trial Registration: ClinicalTrials.gov Identifier: NCT04201561.; Competing Interests: No potential conflict of interest relevant to this article was reported. (Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Parker-Autry, C., et al. (2022). "Examining the Role of Nonsurgical Therapy in the Treatment of Geriatric Urinary Incontinence." Obstetrics and Gynecology 140(2): 243-251.
	OBJECTIVE:To examine the role of physical function impairments on the change in urinary incontinence (UI) symptoms after pelvic floor muscle training in older women. METHOD(S):This is a prospective cohort study of 70 community-dwelling participants, older than age 70 years, with at least moderate incontinence symptoms. A comprehensive pelvic floor and physical function assessment was done at baseline. Individualized pelvic floor muscle training prescriptions with behavioral management strategies to reduce incontinence episodes were provided for 12 weeks. Baseline physical function was determined using the SPPB (Short Physical Performance Battery). A total score of 9 or lower out of 12 indicated impaired physical function, and scores higher than 9 indicated normal physical function. A 3-day bladder diary established daily incontinence episodes. The between-group difference in the change in number of UI episodes, from baseline to 6 weeks, was our primary outcome. Descriptive analyses compared important demographic and clinical characteristics. Longitudinal mixed model linear regression analyses determined the change in incontinence episodes and estimates of improvement based on the presence of impaired physical function and adjusted for age, race, and body mass index (BMI). RESULT(S):Participants' mean+/-SD age was 76.9+/-5.4 years, and 15.7% identified as African American, with no significant differences in age or race between groups. Participants with impaired physical function had higher mean+/-SD BMI (33.6+/-14.5 vs 27.4+/-5.8; P=.03) and more baseline incontinence episodes (4.5+/-2.9 vs 2.7+/-2.1 episodes per day; P=.005) than in women without functional impairment. After 6 weeks of pelvic floor exercises, the change in number of incontinence episodes per day was not different between participants with physical functional impairment compared with women with normal physical function (mean [95% CI]-1.2 [-2.0 to-0.5] vs-0.4 [-1.1 to 0.3], P=.31). Overall, after 12 weeks of pelvic floor muscle training, complete satisfaction with incontinence symptom improvement was low for both groups (41.8% with physical function impairments vs 44.8% with normal physical function; P=.90). CONCLUSION(S):Behavioral therapy including pelvic floor muscle training may not significantly decrease UI symptoms to a degree that is satisfactory in women who are older than 70 years and are seeking treatment for UI, regardless of the presence of physical function impairments.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT03057834.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Parodi, L., et al. (2022). "Complete Uterine Septum, Double Cervix and Vaginal Septum (U2b C2 V1): Hysteroscopic Management and Fertility Outcomes-A Systematic Review." Journal of Clinical Medicine 12(1).
	Background: complete uterine septum, double cervix and vaginal septum is a rare complex Müllerian anomaly affecting patients' quality of life in terms of fertility and pelvic pain. The aim of our review is to gather the studies concerning the diagnosis and treatment this complex malformation and to describe the related fertility outcomes.; Methods: this study was conducted in 2022, according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the protocol was submitted to the International Prospective Register for Systematic Reviews (PROSPERO). PubMed, Scopus and Web of Science electronic databases were searched to find eligible articles. In total, 538 articles were identified through literature research. A total of ten articles satisfied the eligibility criteria and were included in the systematic review.; Results: 86 affected women were evaluated, and 71 of them were treated. Almost all patients included in our research presented with primary infertility or with a history of recurrent miscarriages; half of all patients also reported dyspareunia. After surgical treatment, 47 pregnancies were achieved: 41 live birth and ongoing pregnancies and six spontaneous miscarriages occurred; a significantly lower miscarriage rate was reported after surgical treatment.; Conclusion: hysteroscopic treatment of U2b C2 V1 anomaly can be safely performed, leading to favorable fertility outcomes, measured as the achievement of pregnancy and a reduction in miscarriage rate.

Parpinel, G., et al. (2023). "Survival after sentinel lymph node biopsy for early cervical cancers: a systematic review and meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(12): 1853-1860.
	Background: Sentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing.; Objective: To investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer.; Methods: A systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran Χ 2 test and quantified with Higgins information I2.; Results: The search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13-53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group).; Conclusions: Both 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Parra, L., et al. (2019). "Antiseptics and disinfectants for the treatment of vaginal discharge in non‐pregnant women." Cochrane Database of Systematic Reviews(11).
	This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the safety and effectiveness of antiseptics and disinfectants for the treatment of vaginal discharge in non‐pregnant women.

Parra, N. S., et al. (2023). "The Effectiveness of Pelvic Floor Muscle Exercise in Urinary Incontinence: A Systematic Literature Review and Meta-Analysis." Cureus 15(9): e45011.
	Urinary incontinence (UI) is a prevalent health concern in females over 60, but it is prevalent in a smaller percentage of males. The medical and social elements of UI are crucial. This disorder may cause embarrassment and low self-esteem, reducing social and physical activities. Consequently, this may impair healthy aging. Researchers have shown that pelvic floor muscle training (PFMT) may improve UI symptoms in middle-aged, older, and young people. Clinical practice highlights the importance of PFMT for UI due to its low cost-effectiveness. To assess PFMT's overall efficacy, we conducted a systematic review of the literature (SRL) and a meta-analysis (MA) of randomized clinical trials (RCTs). The previous 10 years of published material were combed using the online databases the Cochrane Library, PubMed, and Google Scholar. Eligible total studies were RCTs referring to the effectiveness of PFMT. The pooled incidence, risk ratio, and 95% confidence interval (CI) of the effectiveness of PFMT were calculated using the fixed effects model. Given the possibility of a between-study variance, we used the fixed effects model rather than the random effects model.

Parry Barbara, L., et al. (2023). "A 1-week sleep and light intervention improves mood in premenstrual dysphoric disorder in association with shifting melatonin offset time earlier." Archives of Women's Mental Health 26(1): 29-37.
	To test the hypothesis that 1 week of combined sleep and light interventions (SALI), which phase-advance (shift earlier) melatonin circadian rhythms, improves mood significantly more than phase-delay (shift later) SALI. After a 2-month diagnostic evaluation for premenstrual dysphoric disorder (PMDD per DSM-5 criteria) in a university clinical research setting, 44 participants enrolled in baseline studies were randomized in the luteal phase at home to (A) a phase-advance intervention (PAI): 1 night of late-night wake therapy (LWT: sleep 9 pm-1 am) followed by 7 days of the morning (AM) bright white light (BWL), or (B) a phase-delay intervention (PDI): 1 night of early-night wake therapy (EWT: sleep 3-7 am) plus 7 days of the evening (PM) BWL. After a month of no intervention, participants underwent the alternate intervention. Outcome measures were mood, the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), and actigraphy (to assess protocol compliance). At baseline, atypical depression correlated positively with phase delay in 6-SMT offset time (r = .456, p = .038). PAI advanced 6-SMT offset from baseline more than PDI (p < .05), and improved raw mood scores more than PDI (p < .05). As hypothesized, percent improvement in mood correlated positively with a phase advance from baseline in 6-SMT offset time (p < .001). Treatment with 1 night of advanced/restricted sleep followed by 7 days of AM BWL (PAI) was more efficacious in reducing PMDD depression symptoms than a PDI; mood improvement occurred in association with phase advance in 6-SMT offset time. Combined SALIs offer safe, efficacious, rapid-acting, well-tolerated, non-pharmacological, non-hormonal, affordable, repeatable home interventions for PMDD. Clinical Trials.gov NCT # NCT01799733. (© 2022. The Author(s).)

Parry Barbara, L., et al. (2023). "Critically-timed sleep+light interventions differentially improve mood in pregnancy vs. postpartum depression by shifting melatonin rhythms." Journal of Affective Disorders 324: 250-258.
	Background: Testing the hypothesis that combined wake + light therapy improves mood in pregnant vs. postpartum depressed participants (DP) by differentially altering melatonin and sleep timing.; Methods: Initially 89 women, 37 pregnant (21 normal controls-NC; 16 DP) and 52 postpartum (27 NCs; 25 DP), were randomized to a parallel trial of a phase-delay intervention (PDI): 1-night of early-night wake therapy (sleep 3-7 am) + 6-weeks of evening bright white light (Litebook Advantage) for 60 min starting 90 min before bedtime, vs. a Phase-advance intervention (PAI): 1-night of late-night wake therapy (sleep 9 pm-1 am) + 6-weeks of morning bright white light for 60 min within 30 min of wake time. Blinded clinicians assessed mood weekly by structured interview, and participants completed subjective ratings, a Morningness-Eveningness questionnaire, actigraphy, and collected 2 overnight urine samples for 6-sulphatoxy melatonin (6-SMT).; Results: In pregnant DP, mood improved more after the PDI vs. PAI (p = .016), whereas in postpartum DP, mood improved more after the PAI vs. PDI (p = .019). After wake therapy, 2 weeks of light treatment was as efficacious as 6 weeks (p > .05). In postpartum DP, PAI phase-advanced 6-SMT offset and acrophase (p < .05), which correlated positively with mood improvement magnitude (p = .003).; Limitations: Small N.; Conclusions: Mood improved more after 2 weeks of the PDI in pregnant DP, but more after 2 weeks of PAI in postpartum DP in which improvement magnitude correlated with 6-SMT phase-advance. Thus, critically-timed Sleep + Light Interventions provide safe, efficacious, rapid-acting, well-tolerated, at-home, non-pharmaceutical treatments for peripartum DP.; Competing Interests: Conflict of interest None. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Parsons Brian, A., et al. (2022). "The Benefits and Harms of Botulinum Toxin-A in the Treatment of Chronic Pelvic Pain Syndromes: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel." European Urology Focus 8(1): 320-338.
	Context: Patients with chronic pelvic pain syndrome (CPPS) may have pain refractory to conventional management strategies. Botulinum toxin A (BTX-A) is a potential therapeutic option.; Objective: To evaluate the benefits and harms of BTX-A injections in the treatment of CPPS.; Evidence Acquisition: A systematic review of the use of BTX-A in the treatment of CPPS was conducted (PROSPERO-ID: 162416). Comprehensive searches of EMBASE, PUBMED, Medline, and SCOPUS were performed for publications between January 1996 and May 2020. Identified studies were screened and selected studies assessed for quality prior to data extraction. The primary outcomes were improvement in pain and adverse events following treatment. Secondary outcomes included quality of life, global response assessment, sexual function, bowel function, and bladder function.; Evidence Synthesis: After screening 1001 abstracts, 16 studies including 11 randomised controlled trials were identified, enrolling 858 patients and covering a range of CPPS subtypes. Most studies showed high risks of bias and confounding across all domains. A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis and calculation of pooled effect estimates of measured outcomes. BTX-A reduced pain significantly in patients with bladder pain syndrome in two studies and in patients with prostate pain syndrome in one study, but no included studies showed benefit for patients with gynaecological pelvic pain. Adverse event reporting was variable and generally poor, but no serious adverse events were described.; Conclusions: Beneficial effects of BTX-A on pain, quality of life, and functional symptoms were seen in patients with certain CPPS subtypes, but the current evidence level is too weak to allow recommendations about BTX-A use for treating CPPS.; Patient Summary: Botulinum toxin A is used to treat different pain disorders, but current studies are of insufficient quality to determine whether it reduces pain and improves quality of life in patients with chronic pelvic pain. Further research is needed. (Copyright © 2021 European Association of Urology. All rights reserved.)

Parveen, R., et al. (2021). "Oral versus vaginal micronized progesterone for the treatment of threatened miscarriage." Pakistan journal of medical sciences 37(3): 628‐632.
	Objectives: This study was planned with an aim to find out the effectiveness of oral versus vaginal micronized progesterone for the treatment of threatened miscarriage. Methods: This randomized controlled trial was conducted at The Department of Obstetrics and Gynaecology, Nishtar Hospital Multan, from August 2019 to January 2020. A total of 136 pregnant women, aged 18 to 45 years having vaginal bleeding were included and divided into two groups (68 women in each group). Participants in the Group‐A were given oral micronized progesterone as 200mg twice a day while Group‐B participants were given vaginal progesterone suppository 400mg once a day. All women were followed up until 20th week of their pregnancy. Outcome was labeled as prevention of miscarriage if woman had no bleeding per vagina and pregnancy went beyond 20th weeks of gestation. Results: In a total of 136 women enrolled, mean age was noted to be 30.85+3.34 years. Overall, mean gestational age was noted to be 9.3+2.7 weeks. A total of 98 women (49 in each group) completed the follow up and were included in the final analysis regarding outcome. Among Groups‐A, 45 (91.8) had prevention of miscarriage while 4 (9.2%) had miscarriage in comparison to 36 (73.5%) in Group‐B had prevention of miscarriage whereas 13 (26.5%) had miscarriage and this difference was statistically significant in between the both study groups as women in Group‐A had significantly better outcome in terms of prevention of miscarriage. (P value = 0.0164). Conclusion: The use of oral micronized progesterone was found to be significantly more effective than vaginal progesterone in women with threatened miscarriage.

Pasalak, S. I., et al. (2024). "Evaluation of the Nurse-Led Symptom Management Program for Patients With Gynecologic Cancer Undergoing Chemotherapy." Cancer Nursing 47(1): 31-42.
	Background Patients with cancer experience symptoms concurrently. Nurses need to make multisymptom management and educate patients about self-management strategies. Objective The aim of this study was to evaluate the effect of a nurse-led symptom management program (NL-SMP), developed based on the Symptom Management Model, quality of life (QoL), and symptom severity of women with gynecological cancer undergoing chemotherapy. Methods This randomized controlled study sample consisted of 41 women receiving chemotherapy at an outpatient clinic in Istanbul, Turkey, between November 2018 and December 2019. European Organisation for Research and Treatment of Cancer Quality-of-Life Scale, Edmonton Symptom Assessment Scale, and Modified Brief Sexual Symptom Checklist-Women were used to collect data. Women were randomly assigned to 2 groups: intervention (n = 21) and control (n = 20). The intervention group attended the NL-SMP in addition to usual care. Data were collected at the first (time 1), third (time 2), and last chemotherapy cycle (time 3). Repeated measures analysis of variance, Cochran-Q, and t tests were used to analyze the data. Results In the intervention group, the QoL was significantly higher; symptom severity was lower than that of the control group at time 2 and time 3. At time 3, more women in the control group reported at least 1 sexual difficulty and were not satisfied with their sexual function, whereas there was no change for women in the intervention group. Conclusion The NL-SMP, which consisted of systematic symptom assessment, prioritization of symptoms, providing symptom, and patient-specific education, decreased deterioration in the QoL and symptom severity of women. Implications for Practice Conducting multisymptom assessments, prioritizing symptoms, providing symptom- and patient-specific education, and supporting symptom self-management throughout treatment can lead to effective symptom management.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Pascon, B., et al. (2020). "Effectiveness of the pelvic floor muscle training on muscular dysfunction and pregnancy specific urinary incontinence in pregnant women with gestational diabetes mellitus: A systematic review protocol." PloS One 15(12 December): e0241962.
	Background There is ample evidence that gestational diabetes mellitus has a direct influence on urinary incontinence and pelvic floor muscles. There are no standardized pelvic floor muscle exercise programs in the literature for the physiotherapy and differ in the type of exercise, intensity, type and duration of application, and the frequency and duration of treatment sessions. The aim of this systematic review will be to investigate that Pelvic Floor Muscle Training can prevent and/or decrease the pregnancy specific urinary incontinence in women with gestational diabetes mellitus or gestational hyperglycemia. Methods We will perform a systematic review according to the Cochrane methodology of Randomized Controlled Trials. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases, with the date of consultation until June 2020. The MeSH terms used will be "Pregnancy", "Hyperglycemia", "Diabetes Mellitus, Type 2", "Diabetes Mellitus, Type 1", "Pregnancy in Diabetics", "Diabetes, Gestational", "Urinary Incontinence", "Pelvic Floor Muscle Strength". Primary outcomes: improvement or cure of pregnancy specific urinary incontinence (which can be assessed by questionnaires, and tools such as tampon test, voiding diary, urodynamic study). Secondary Outcomes: improvement of pelvic floor muscle strength (pelvic floor functional assessment, perineometer, electromyography, functional ultrasonography), improved quality of life (questionnaires), presence or absence of postpartum Urinary Incontinence and adverse effects. Quality assessment by Cochrane instrument. Metanalysis if plausible, will be performed by the software Review Manager 5.3. Discussion The present study will be the first to analyze the effectiveness of pelvic floor exercises in pregnant women with Gestational Diabetes Mellitus or Hyperglycemia, who suffer from pregnancy specific urinary incontinence. Randomized Controlled Trials design will be chosen because they present the highest level of evidence. It is expected to obtain robust and conclusive evidence to support clinical practice, in addition to promoting studies on the theme and contributing to new studies.Copyright © 2020 Barbosa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Pasquier, E., et al. (2019). "Hydroxychloroquine for prevention of recurrent miscarriage: study protocol for a multicentre randomised placebo-controlled trial BBQ study." BMJ Open 9(3): e025649.
	Introduction: Recurrent miscarriage (RM), defined by three or more consecutive losses during the first trimester of pregnancy, affects 1%-2% of fertile couples. Standard investigations fail to reveal any apparent cause in ~50% of couples. However, on the basis of animal models and clinical studies, several hypotheses have been put forward concerning underlying mechanisms of RM: altered ovarian reserve, progesterone defect, thrombotic and/or endothelial dysfunction and immunological disturbances. Nonetheless, no study has yet reached conclusive beneficial clinical evidence for a potential treatment in unexplained RM. Hydroxychloroquine (HCQ) is a molecule with extensive safety data during pregnancy. The pharmacological properties of HCQ (eg, antithrombotic, vascular protective, immunomodulatory, improved glucose tolerance, lipidlowering and anti-infectious) could be effective against some mechanisms of unexplained RM. Furthermore, eventhough clinical benefit of HCQ is suggested in prevention of thrombotic and late obstetric events in antiphospholipid (APL) syndrome, there are no data suggesting the benefit of HCQ in RM in the presence of APL antibodies.; Methods and Analysis: Taken all together and given the low cost of HCQ, the aim of this multicentre, randomised, placebo-controlled, double-blind study is to investigate whether HCQ would improve the live birth rate in women with RM, irrespective of maternal thrombophilic status: (1) no known thrombophilia, (2) inherited thrombophilia or (3) APL antibodies. The primary end point is a live and viable birth. After confirming eligibility and obtaining consent, 300 non-pregnant women will be randomised into two parallel groups for a daily oral treatment (HCQ 400 mg or placebo), initiated before conception and stopped at 10 weeks' gestation. If pregnancy does not occur after 1 year, the treatment will be stopped.; Ethics and Dissemination: Agreement from the French National Public Health and Drug Security Agency (160765A-22) and ethical approval from the Committee for the Protection of Persons of NORD-OUEST I (2016-001330-97) have been obtained.; Trial Registration Numbers: NCT0316513; Pre-results.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patatanian, E. and R. Nguyen David (2022). "Brexanolone: A Novel Drug for the Treatment of Postpartum Depression." Journal of pharmacy practice 35(3): 431-436.
	Objectives: To review the pharmacology, efficacy, and safety of Brexanolone and define its role in the treatment of postpartum depression.; Date Sources: A MEDLINE/PubMed search was conducted (1980-May 2020) using the following keywords: postpartum depression, antidepressants, pharmacologic therapy, drug therapy, and brexanolone to identify relevant articles.; Study Selection/data Extraction: Literature search was limited to human studies published in the English language. Phase I, II, and III studies evaluating the pharmacology, efficacy, safety of brexanolone for postpartum depression were included. Bibliographies of relevant articles evaluating postpartum depression and treatment were reviewed for additional citations and background information.; Data Synthesis: Brexanolone is a soluble, proprietary, injectable formulation of allopregnanolone, a neuroactive steroid that modulates neuronal excitability. Allopregnanolone levels increase during pregnancy and decrease substantially after birth. These fluctuations have profound effects on anxiety and depression. Three clinical trials established the efficacy and safety of brexanolone in the treatment of postpartum depression. In all 3 trials, brexanolone had an acceptable safety profile and was well tolerated. The most common adverse effects were loss of consciousness, sedation, dry mouth, headache, dizziness, and flushing. Due to sudden loss of consciousness and excessive sedation, continuous pulse oximetry is recommended.; Conclusion: Brexanolone has a novel mechanism of action and appears to be safe and effective for the treatment of moderate to severe postpartum depression. At present, high cost, serious adverse effects, and restricted access may limit its use in clinical practice.

Patel, S., et al. (2022). "Randomized Clinical Study On Medical Versus Manual Vacuum Aspiration For Medical Termination Of Pregnancy In First Trimester." Journal of Pharmaceutical Negative Results 13: 9079‐9086.
	Aims & objectives ‐ Primary Objective ‐To compare and evaluate the efficacy, benefits and risks of medical method versus manual vacuum aspiration method for medical termination of pregnancy. Secondary Objective: 1.Study the incidence of complete evacuation 2. Compare duration of bleeding following termination 3. Compare the complications and side effects 4. Assess the contraception usage 5. Evaluate the backup require in cases of incomplete abortion. ‐ in both the methods of termination of pregnancy. Materials and Methods ‐A hospital based, Time bound, Prospective, Randomized, Comparative study where clients seeking medical termination of pregnancy with less than or equal to 9 weeks of gestation were allocated in two groups by Randomization. Group A‐ Medical method and Group B‐ Manual vacuum aspiration. Data regarding age, parity, side effects, complications, duration of bleeding, backup was studied & compared by statistical analysis. Results ‐ Mean age of study population was 27.65 ± 4.402 years. The mean gestational age was 49.21 ± 6.578 days. Complete abortion rate was 95.45%. Mean duration of bleeding was 7.36 ± 3.57 days. Abdominal pain was commonest side effect reported in 60% clients. Complication rate was 5.45%. Post abortion contraception acceptance was 75.25%. Conclusion ‐ For termination of first trimester pregnancy up to 9 weeks both methods can be used with similar efficacy. The clients undergoing medical method of abortion should be counselled about side effects like nausea, diarrhea, fever and increased duration of bleeding and for accepting regular method of contraception to prevent future unwanted pregnancy.

Pather, K., et al. (2021). "The ThermiVa In Genital Hiatus Treatment (TIGHT) Study." Sexual medicine 9(6).
	Introduction: Vaginal laxity or the sensation of vaginal looseness affects anywhere from 24% to 50% of postpartum women. Aim: To evaluate the efficacy and safety of the ThermiVa (ThermiAesthetics, TX, USA) monopolar radiofrequency device in the treatment of vulvovaginal laxity and sexual dysfunction Methods: The TIGHT study was a prospective single blinded randomized sham‐control trial conducted over 3 sites in Australia and India. The study included parous woman over the age of 18 who complained of vaginal laxity/looseness. Participants were randomized into a treatment group and a sham group. Patients in the treatment group were treated with an active probe, whereas, women in the placebo group were treated with sham probes that only reached subtherapeutic temperatures. Main Outcome Measures: Subjective success was determined by improvement in the Female Sexual Function Index (FSFI), Vaginal Laxity Questionnaire (VLQ), Vaginal Flatus Score (VFS), and the Vaginal laxity Bother Score (VLBS). Objective success was measured via the Modified Oxford Score (MOS) and Genital Hiatus (GH) length. Results: Sixty‐three participants were recruited (sham n = 29, treatment n = 34). In the treatment group, FSFI scores improved at 3 months (mean difference 8‐points, P value.02), and at 6 months (mean difference 5‐points, P value.07). At baseline 89.7% and 87.2% of patients in the sham and treatment groups, respectively, classified themselves as “loose” on the VLQ. At 6 months 73.1% of patients in the sham group still identified as “loose” compared to 32.4% of patients in the active group (P value.01). Subjective success was also noted in the VLBS (P value.02). Results pertaining to VLFS, MOS, and GH did not reveal statistically significant results. Conclusion: Treatment with ThermiVa was associated with a modest subjective improvement in vaginal laxity and sexual dysfunction and proved to be safe over the 6‐month trial period. Pather K, Dilgir S, Rane A. The ThermiVa In Genital Hiatus Treatment (TIGHT) Study. Sex Med 2021;XX:XXXXXX.

Patnam, R., et al. (2022). "A Randomized Clinical Trial Comparing the Efficacy and Safety of 2% Versus 4% Chlorohexidine Gluconate for Surgical Preparation of the Vagina." Female Pelvic Medicine & Reconstructive Surgery 28(7): 400-407.
	Importance: There have been no studies comparing 2% and 4% chlorhexidine gluconate (CHX) for vaginal surgical site preparation despite both commonly being used.; Objectives: The primary objective was to assess the noninferiority of 2% CHX versus 4% CHX to reduce bacterial contamination rates at 60 minutes after surgical preparation of the vagina. Secondary objectives were to assess differences in colony-forming units and the sensation of postoperative vaginal burning and pain.; Study Design: This is a single-blinded randomized controlled trial of women who underwent vaginal prolapse surgery. Study participants were randomized into 2 groups: 2% CHX versus 4% CHX. Two vaginal bacterial cultures were collected: (1) preoperatively before vaginal preparation and (2) intraoperatively at 60 minutes. A questionnaire on vaginal pain and burning was administered preoperatively and postoperatively. For our sample size, assuming that 2% CHX would have double the contamination rate of 4% CHX, 26 participants were needed per group to demonstrate noninferiority.; Results: Sixty-one women participated in the study. There were no differences in baseline demographics, length of surgery, or surgical procedures. For our primary outcome, the postpreparation contamination rates were 7% for 2% CHX versus 10% for 4% CHX, with a difference of 3% ( P = 0.52). This difference did meet the criteria for noninferiority. Secondary outcomes were not different between groups.; Conclusions: Two percent CHX is noninferior to 4% CHX in reducing vaginal bacterial contamination at 60 minutes after vaginal surgical site preparation, with low rates of postpreparation contamination and vaginal discomfort.; Competing Interests: The authors have declared they have no conflicts of interest. (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Pattanayak, L., et al. (2021). "Comparison of dosimetric data of bone marrow between standard IMRT and bone marrow sparing IMRT in carcinoma cervix." Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology 26(6): 976-983.
	BACKGROUND: The aim of the study was to assess the dosimetric comparison of bone marrow between standard IMRT(SD-IMRT) and bone marrow sparing IMRT (BMS-IMRT) among carcinoma cervix patients who underwent radical or adjuvant chemoradiation in a tertiary cancer center. MATERIALS AND METHODS: Forty eligible patients of histo-pathologically proven carcinoma cervix were enrolled in the study that was randomized on a 1:1 basis between SD-IMRT and BMS-IMRT from July 2018 to October 2019. The whole pelvis, bilateral femoral heads, and upper 1/3rd femur were contoured using the whole bone technique as a surrogate marker for the bone marrow. In both arms, V10, V20, and V40, bone marrow was noted along with mean, maximum, minimum dose, and total volume. DVH for the bone marrow in both arms was compared using the unpaired student t-test. RESULTS: We found no significant difference in the mean of various parameters in SD-IMRT arm vs. BMS IMRT arm - for the bone marrow: V10 (89 ± 4.3% vs. 86.7 ± 3.7%), V20 (73.2 ± 5.3% vs. 73.1 ± 4.5%), V40 (23.9 ± 5.4% vs. 26.6 ± 7.4%) and, similarly, for mean dose (28.1 ± 3.5% vs. 28.1 ± 1.8%), maximum dose (53.4 ± 0.58% vs. 53.2 ± 0.58%), minimum dose (0.33 ± 0.18% vs. 0.38 ± 0.38%), total volume (961 ± 110 cc vs. 901 ± 152 cc). CONCLUSION: This study shows no statistically significant difference in dosimetry between the two groups, which suggests that SD-IMRT spares the bone marrow adequately. Therefore, the need for BMS-IMRT using the present contouring technique does not give any added advantage over SD-IMRT. However, large sample size, other novel contouring technique, and multivariate analysis are needed to reach a definite conclusion.

Patten Rhiannon, K., et al. (2023). "Longitudinal affective response to high-intensity interval training and moderate-intensity continuous training in overweight women with polycystic ovary syndrome: A randomised trial." Psychology of sport and exercise 64: 102325.
	Background: Women with polycystic ovary syndrome (PCOS) experience general and PCOS-specific barriers that limit their engagement with exercise and contribute to high attrition from exercise programs, hindering the potential benefits of exercise to address their increased cardio-metabolic risk. A positive remembered affective response can predict future intentions and adherence to exercise prescription.; Objectives: To compare the longitudinal changes in remembered affect to high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in women with PCOS and to determine whether longitudinal changes in remembered affect are correlated with changes in fitness, body mass index, adherence and exercise enjoyment.; Methods: Physically inactive, overweight women with PCOS were randomly assigned to 12 weeks of either HIIT (n = 15) or MICT (n = 14) (3 sessions per week). Remembered affective valence (Feeling Scale) was collected after each exercise session. Cardiorespiratory fitness (VO 2peak ) was assessed at baseline and post-intervention. Exercise enjoyment was assessed post-intervention.; Results: The longitudinal changes in the remembered affect were more positive in the HIIT group compared to MICT (β = 0.017, p = 0.047). HIIT was also considered more enjoyable than MICT (p = 0.002). Adherence was high in both groups (>90%). We found a moderate correlation with longitudinal changes between the remembered affect and change in fitness (r s = 0.398) and exercise enjoyment (r s = 0.376) using the combined group, however, these were not statistically significant (p = 0.054 and p = 0.064, respectively).; Conclusions: HIIT demonstrated a more positive longitudinal remembered affective response and greater exercise enjoyment compared to MICT in overweight women with PCOS.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Patten Rhiannon, K., et al. (2020). "Exercise Interventions in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis." Frontiers in Physiology 11: 606.
	Background: Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive and metabolic manifestations. Exercise training has consistently been found to result in improved clinical outcomes in women with PCOS, but shortfalls with exercise prescription are evident. The aim of this systematic review and meta-analysis was to identify exercise intervention characteristics that provide favourable outcomes in women with PCOS. Methods: A systematic review of published literature was conducted using EBSCOhost and Ovid Medline up to May 2019. The review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines as per our PROSPERO protocol (CRD42018088367). Randomised controlled trials, non-randomised controlled trials, and uncontrolled trials that evaluated an exercise intervention of at least moderate intensity in women with PCOS were included. Meta-analyses were performed using general linear mixed modelling and Bayesian inferences about effect magnitudes. Results: Thirty-three articles were identified for systematic review of which 19 were meta-analysed. Intervention duration ranged from 6 to 26 weeks. A total number of 777 women were included in the meta-analysis. The meta-analysis found that improvements in health outcomes are more dependent on exercise intensity rather than dose. Fixed effects analysis reported a moderate increase in VO 2peak (24.2%; 90% CL, 18.5-30.1), and small reductions in HOMA-IR (-36.2%; 90% CL, -55.3 to -9.0), and waist circumference (-4.2%; 90% CL -6.0 to -2.3) as a result of vigorous intensity exercise. These results are confirmed in the predicted analysis which reported the greatest improvements in VO 2peak , BMI, and waist circumference after vigorous intensity exercise alone or when combined with diet, particularly for women with clinically adverse baseline values. Conclusions: Exercise training in the management of PCOS is becoming more common. Results from our analysis support the use of exercise and suggest that vigorous intensity exercise may have the greatest impact on cardiorespiratory fitness, body composition, and insulin resistance. Our results indicate that, a minimum of 120 min of vigorous intensity per week is needed to provide favourable health outcomes for women with PCOS with studies of longer duration required to evaluate outcomes with sustained exercise. (Copyright © 2020 Patten, Boyle, Moholdt, Kiel, Hopkins, Harrison and Stepto.)

Patten Rhiannon, K., et al. (2023). "Efficacy of high-intensity interval training for improving mental health and health-related quality of life in women with polycystic ovary syndrome." Scientific Reports 13(1): 3025.
	Women with PCOS have substantially greater symptoms of depression and anxiety, and a lower health-related quality of life (HRQoL) compared to women without PCOS. The aim of this study was to determine if high-intensity interval training (HIIT) could provide greater improvements in mental health outcomes than standard moderate-intensity continuous training (MICT). Twenty-nine overweight women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% HR peak , N = 15) or HIIT (> 90% HR peak , N = 14). Outcome measures included symptoms of depression, anxiety and stress (DASS-21), general HRQoL (SF-36) and PCOS specific HRQoL (PCOSQ) collected at baseline and post-intervention. Reductions in depression (Δ - 1.7, P = 0.005), anxiety (Δ - 3.4, P < 0.001) and stress (Δ - 2.4, P = 0.003) scores were observed in the HIIT group, while MICT only resulted in a reduction in stress scores (Δ - 2.9, P = 0.001). Reductions in anxiety scores were significantly higher in the HIIT group compared to the MICT group (β = - 2.24, P = 0.020). Both HIIT and MICT significantly improved multiple domain scores from the SF-36 and PCOSQ. This study highlights the potential of HIIT for improving mental health and HRQoL in overweight women with PCOS. HIIT may be a viable strategy to reduce symptoms of depression and anxiety in women with PCOS, however, large-scale studies are required to confirm these findings.Trial registration number: ACTRN12615000242527. (© 2023. The Author(s).)

Patten Rhiannon, K., et al. (2021). "Effectiveness of exercise interventions on mental health and health-related quality of life in women with polycystic ovary syndrome: a systematic review." BMC public health 21(1): 2310.
	Background: Polycystic ovary syndrome (PCOS) is a complex condition, impacting cardio-metabolic and reproductive health, mental health and health-related quality of life. The physical health benefits of exercise for women with PCOS are well-established and exercise is increasingly being recognised as efficacious for improving psychological wellbeing. The aim of this review was to summarise the evidence regarding the effectiveness of exercise interventions on mental health outcomes in women with PCOS.; Methods: A systematic search of electronic databases was conducted in March of 2020. Trials that evaluated the effect of an exercise intervention on mental health or health-related quality of life outcomes in reproductive aged women with diagnosed PCOS were included. Methodological quality was assessed using the modified Downs and Black checklist. Primary outcomes included symptoms of depression and anxiety, and health-related quality of life.; Results: Fifteen articles from 11 trials were identified and deemed eligible for inclusion. Exercise demonstrated positive improvements in health-related quality of life in all of the included studies. Half of included studies also reported significant improvements in depression and anxiety symptoms. There was large variation in methodological quality of included studies and in the interventions utilised.; Conclusions: The available evidence indicates that exercise is effective for improving health-related quality of life and PCOS symptom distress. Exercise also shows some efficacy for improving symptoms and/or prevalence of depression and anxiety in women with PCOS. However, due to large heterogeneity of included studies, conclusions could not be made regarding the impact of exercise intervention characteristics. High-quality trials with well reported exercise intervention characteristics and outcomes are required in order to determine effective exercise protocols for women with PCOS and facilitate translation into practice. (© 2021. The Author(s).)

Patterson, J., et al. (2019). "PTSD post-childbirth: a systematic review of women's and midwives' subjective experiences of care provider interaction." Journal of Reproductive and Infant Psychology 37(1): 56-83.
	Objective: Review primary research regarding PTSD Post-Childbirth (PTSD-PC) that focussed on Quality of Provider Interaction (QPI) from the perspective of women who developed PTSD-PC, or midwives. Background(s): Up to 45% of women find childbirth traumatic. PTSD-PC develops in 4% of women (18% in high-risk groups). Women's subjective experiences of childbirth are the most important risk factor in the development of PTSD-PC, with perceived QPI being key. Method(s): A systematic search was performed for PTSD-PC literature. Reviewed papers focussed on either women's subjective childbirth experiences, particularly QPI, or midwives' perspectives on QPI. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) tools, and a narrative synthesis of findings produced. Result(s): Fourteen studies were included. Three features of QPI contribute towards developing PTSD-PC: interpersonal factors; midwifery care factors; and lack of support. Conclusion(s): QPI is a significant factor in the development of PTSD-PC and the identified key features of QPI have potential to be modified by midwives. The development of guidelines for midwives should be grounded on evidence highlighted in this review, along with further high-quality qualitative research exploring QPI from the perspective of women with PTSD-PC, but also midwives' knowledge and needs regarding their role within QPI.Copyright © 2018, © 2018 Society for Reproductive and Infant Psychology.

Paul, Y. (2022). "Endometriosis and Health Care System Utilization in British Columbia." ClinicalTrials.gov.
	HYPOTHESIS Aim 1: The investigators hypothesize that health care costs for patients being cared for in our clinic will be higher in the three years preceding their time with us than the years following their discharge. The investigators hypothesize that the overall cost of the interdisciplinary clinic, including physiotherapist, counsellor and nurse salaries and administrative support, will be less than overall cost savings to the system from reduced utilization of health care resources after discharge. Aim 2: The investigators hypothesize that comorbidities associated with central nervous system sensitization and biomarkers including somatic mutations and local neurogenesis/neuroinflammation are linked to persistent pain and disease recurrence after endometriosis surgery, which results in increased risk of re-operation and health care utilization after surgery. Aim 3: The pandemic cohort will have increased health care system utilization, and also poorer health system outcomes after care the centre. Aim 4: People with endometriosis, utilizing different case definitions, will experience higher health care use and worse pregnancy outcomes, compared to people without endometriosis.

Paulussen, M., et al. (2021). "Fertility-related quality of life in subfertile women undergoing transvaginal hydrolaparoscopy versus hysterosalpingography as a first-line tubal patency test." Human reproduction (Oxford, England) 36(SUPPL 1): i349‐i350.
	Study question: Is there a difference in fertility‐related quality of life (QoL) in subfertile women undergoing transvaginal hydrolaparoscopy (THL) versus hysterosalpingography (HSG) as a first‐line tubal‐patency test? Summary answer: In subfertile women undergoing first‐line tubal patency testing, THL and HSG resulted in comparable fertility‐related QoL. What is known already: Both subfertility itself and subfertility treatment can have a significant impact on QoL. Tubal patency testing as part of fertility work‐up is also known as a potential stressor. Pain scores for THL are significantly lower than for HSG (VAS 4.7 vs 5.4 ; SD:2.5, p 0.038), but acceptability of the procedures was found to be comparable. Fertility‐related QoL has not yet been studied in women undergoing tubal patency testing. Study design, size, duration: We used data from a randomised clinical trial performed in 4 Dutch teaching hospitals, NTR3462. Between May 2013 and October 2016, we randomly assigned 300 subfertile women to THL or HSG with live birth as primary outcome. We performed a standardized questionnaire study as part of a randomised controlled trial comparing THL and HSG in the work‐up for subfertility. Participants/materials, setting, methods: Women were eligible if they were undergoing a fertility work‐up with an indication for evaluation of tubal patency testing. Fertility‐related QoL was measured six weeks after the procedure with the validated FertiQoL questionnaire, which produces a Core (total) score and four subscale domains: Emotional, Relational, Social, and Mind‐Body. FertiQoL scores for the Core score and subscales between THL and HSG were compared using Mann‐Whitney‐U test and multiple linear regression analysis. Main results and the role of chance: We allocated 149 women to THL and 151 to HSG. The questionnaire was completed by 84 women in the THL group (response rate 56%) and 96 women in the HSG group (response rate 64%). Core scores were 74.6 ±12.8 for THL and 73.4 ±12.4 for HSG (p=0.39). Scores for the Emotional domain were 64.5 ±19.0 for THL versus 66.0 ±16.3 (p=0.67) for HSG. Scores for the 'Mind‐body' domain for THL were 76.9 ±15.6 versus 74.1 ±18.0 for HSG (p=0.42), scores for the Relational domain were 79.2 ±12.9 for THL and 76.9 ±15.6 for HSG (p=0.21). Scores for the Social domain for THL were 77.9 ±15.1 versus 76.7±14.1, (p=0.42). The optional 'Treatment FertiQol' was completed by 156 women. Total scores were 77.5 ±12.1 for THL versus 73.8 ±13.1 (p=0.08) for HSG. The multiple linear regression analysis showed only a statistical significant positive effect of higher age on the score for the Emotional domain (B:0.90, p=0.015). Limitations, reasons for caution: One of the main limitations of this study was a response rate of 60%. Although this is considered an acceptable rate within questionnaire research, this could lead to selection bias. Wider implications of the findings: In subfertile women, tubal patency testing with THL versus HSG did not result in differences in fertility‐related QoL.

Pautier, P., et al. (2021). "A single-arm multicentre phase II trial of doxorubicin in combination with trabectedin in the first-line treatment for leiomyosarcoma with long-term follow-up and impact of cytoreductive surgery." ESMO Open 6(4): 100209.
	BACKGROUND: Uterine leiomyosarcomas (U-LMSs) and soft tissue leiomyosarcomas (ST-LMSs) are rare tumours with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with manageable toxicity. Herein, we report the updated and long-term results of progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Patients received 60 mg/m2 intravenous doxorubicin followed by trabectedin 1.1 mg/m2 as a 3-h infusion on day 1 and pegfilgrastim on day 2, every 3 weeks, up to six cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. RESULTS: One-hundred and eight patients were enrolled, mainly with metastatic disease (85%), and 20 patients (18.5%) had surgical resection of metastases after chemotherapy. With a median follow-up of 7.2 years [95% confidence interval (CI) 6.9-8.2 years], the median PFS was 10.1 months (95% CI 8.5-12.6 months) in the whole population, and 8.3 months (95% CI 7.4-10.3 months) and 12.9 months (95% CI 9.2-14.1 months) for U-LMSs and ST-LMSs, respectively. The median OS was 34.4 months (95% CI 26.9-42.7 months), 27.5 months (95% CI 17.9-38.2 months), and 38.7 months (95% CI 31.0-52.9 months) for the whole population, U-LMSs, and ST-LMSs, respectively. The median OS of the patients with resected metastases was not reached versus 31.6 months in the overall population without surgery (95% CI 23.9-35.4 months). CONCLUSIONS: These updated results confirm the impressive efficiency of the doxorubicin plus trabectedin combination given in first-line therapy for patients with locally advanced/metastatic LMS in terms of PFS and OS. Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing the doxorubicin plus trabectedin combination versus doxorubicin alone in first-line therapy in metastatic LMSs, are pending.

Pautier, P., et al. (2021). "Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial." Journal of Clinical Oncology 39(15 SUPPL).
	Background: In the Phase III PAOLA‐1/ENGOTov25 trial (NCT02477644), the addition of maintenance olaparib to bev in pts with newly diagnosed advanced high‐grade ovarian cancer (HGOC) resulted in a significant PFS benefit, particularly in HRD‐positive (HRD+) pts (hazard ratio [HR] 0.33; 95% CI 0.25‐0.45) (Ray‐Coquard et al.NEJM 2019). We explored efficacy in HRD+ pts by disease stage. Methods: Pts with newly diagnosed, FIGO stage III‐IV HGOC in response after platinum‐based chemotherapy + bev received bev (15 mg/kg q3w for 15 months [mo]) + either olaparib (300 mg bid for 24 mo) or placebo (pbo). This exploratory analysis evaluated PFS (data cut‐off [DCO]: Mar 22 2019) and PFS2 (DCO: Mar 22 2020) in HRD+ pts (tumor BRCA1/BRCA2 mutation [tBRCAm] or genomic instability score [Myriad myChoice HRD Plus] ≥42) by FIGO stage. Results: 387/806 randomized pts (48%) were HRD+; 272/387 (70%) had stage III disease and 115/387 (30%) had stage IV disease. 153 (56%) HRD+ stage III pts and 61 (53%) HRD+ stage IV pts had a tBRCAm. Among HRD+ stage III pts, 172 (63%) had upfront surgery (51/172 [30%] had residual disease) and 90 (33%) had interval surgery (19/90 [21%] had residual disease); 52 (45%) HRD+ stage IV pts had upfront surgery (34/52 [65%] had residual disease) and 55 (48%) had interval surgery (18/55 [33%] had residual disease). Median follow‐up for PFS and PFS2 was respectively 24.8 and 37.2 mo in HRD+ stage III pts and 24.0 and 37.0 mo in HRD+ stage IV pts. Median PFS, PFS2 and HRs are in the Table. Among HRD+ stage III pts, 36‐mo PFS2 (olaparib + bev vs pbo + bev) was 74% vs 60%; among HRD+ stage IV pts, 53% vs 30%. Among HRD+ stage III pts with no residual disease after upfront surgery, HR (95% CI) for PFS was 0.15 (0.07‐0.30) and for PFS2 was 0.22 (0.06‐0.67). Among HRD+ stage III pts with residual disease after upfront surgery or who received neoadjuvant chemotherapy, or HRD+ stage IV pts, HR (95% CI) for PFS was 0.38 (0.27‐ 0.53) and PFS2 was 0.68 (0.46‐1.03). Conclusions: In the PAOLA‐1 study, maintenance olaparib + bev provided a PFS and PFS2 benefit over pbo + bev in HRD+ pts, irrespective of FIGO stage and residual disease after upfront surgery.

Pautier, P., et al. (2022). "Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial." The Lancet. Oncology 23(8): 1044-1054.
	Background: Metastatic leiomyosarcomas have a poor prognosis, and currently doxorubicin alone is used as the standard first-line treatment. Doxorubicin combined with trabectedin has shown promising results in phase 1 and 2 studies. We aimed to identify and compare the progression-free survival of patients with metastatic or unresectable uterine or soft tissue leiomyosarcoma treated with doxorubicin and trabectedin combined as first-line therapy versus doxorubicin alone in a phase 3 trial.; Methods: LMS-04 was a randomised, multicentre, open-label, superiority phase 3 trial, which included patients from 20 centres of the French Sarcoma Group (anticancer centers or hospitals with an oncological unit) in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-1, and had metastatic or relapsed unresectable leiomyosarcomas that had not previously been treated with chemotherapy. Patients were randomly assigned (1:1), by means of an interactive web response system (permuted blocks of different sizes from two to six), to receive either intravenous doxorubicin alone (75 mg/m 2 ) once every 3 weeks for up to six cycles or of intravenous doxorubicin (60 mg/m 2 ) plus intravenous trabectedin (1·1 mg/m 2 ) once every 3 weeks up to six cycles followed by maintenance with trabectedin alone. Surgery for residual disease was allowed in both groups after six cycles of treatment. Randomisation was stratified by tumour location (uterine vs soft tissue) and disease (locally advanced vs metastatic). The primary endpoint was progression-free survival assessed by blinded independent central review and according to Response Evaluation Criteria in Solid Tumours 1.1 criteria. Efficacy analyses were performed on all randomly assigned patients, based on the intention-to-treat principle. The safety population included all randomly assigned patients who received at least one cycle of treatment. This trial is registered with ClinicalTrials.gov, NCT02997358, and is closed to enrolment.; Findings: Between Jan 18, 2017, and March 21, 2019, 150 patients were enrolled (67 with uterine leiomyosarcomas and 83 with soft tissue leiomyosarcomas) and included in the intention-to-treat population: 76 in the doxorubicin alone group and 74 in the doxorubicin plus trabectedin group. The median duration of follow-up was 36·9 months (IQR 30·0-43·2) in the doxorubicine group and 38·8 months (32·7-44·2) in the doxorubicin plus trabectedin group. Median progression-free survival was significantly longer with doxorubicin plus trabectedin versus doxorubicin alone (12·2 months [95% CI 10·1-15·6] vs 6·2 months [4·1-7·1]; adjusted hazard ratio 0·41 [95% CI 0·29-0·58]; p<0·0001). The most common grade 3-4 adverse events were neutropenia (ten [13%] of 75 patients in the doxorubicin alone group vs 59 [80%] in the doxorubicin plus trabectedin group), anaemia (four [5%] vs 23 [31%]), thrombocytopenia (0 vs 35 [47%]), and febrile neutropenia (seven [9%] vs 21 [28%]). Nine (12%) patients in the doxorubicin alone group and 15 (201%) patients in the doxorubicin plus trabectedin group has serious adverse events. There was only one treatment-related death, reported in the doxorubicin alone group (cardiac failure).; Interpretation: Doxorubicin plus trabectedin in first-line therapy was found to significantly increase progression-free survival in patients with metastatic or unresectable leiomyosarcomas compared with doxorubicin alone, despite a higher but manageable toxicity, and could be considered an option for the first-line treatment of metastatic leiomyosarcomas.; Funding: PharmaMar.; Competing Interests: Declaration of interests PP has received research funding from PharmaMar, Onxeo (Bristol Myers Squibb [BMS]; all fees to their institution); has received honoraria for lectures and presentations from Merck Shape & Dohme (MSD) and Clovis; has received consultancy fees from MSD, PharmaMar, AstraZeneca, Roche, Onxeo, GlaxoSmithKline (GSK), and Clovis; and has received support for travel or meetings f om GSK, PharmaMar, Roche, AstraZeneca, and Amgen. AI has received research funding from AstraZeneca, Bayer, BMS, MSD, Merck, and Roche; and consulting fees from AstraZeneca, Bayer, BMS, MSD, Merck, and Roche. SP-N has received support for travel or attending meetings from PharmaMar. CC has been on a data safety monitoring board or advisory board for Ipsen, Pfizer, ESAI, MSD, and BMS. NF has received support for travel or meetings from PharmaMar. PB-R has received support for travel or attending meetings from Takeda, Pfizer, and Pharmamar; and has received consultancy fees from Ipsen. VL-L has been on a on a data safety monitoring board or advisory board for Ipsen. IR-C has received research funding from BMS, MSD, and GSK; has received honoraria for lectures and presentations from GSK, AstraZeneca, Clovis, Agenus, Deciphera, Mersana, MAcrogenics, Pharmamar, Roche, Novartis, and ESAI; support for attending meetings or travel from AstraZeneca, GSK, Clovis, and Roche; and participated on a data safety monitoring board or advisory board for the Athena trial. EK has received consultancy fees, honoraria for lectures and presentations, support for travel or attending meetings from, and has been on a data safety monitoring board or advisory board for, AstraZeneca, Roche, Sanofi, Tesaro, GSK, and Leopharma. AB has received consultancy fees from Roche. NI has received support for travel or attending meetings from AstraZeneca, Roche, PharmaMar, and Novartis; has been on a data safety monitoring board or advisory board for Ipsen, Daïchi, Senkyo, Transgen, Pfizer, Magen, BMS, and ESAI. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pavlović, R. T., et al. (2019). "The Safety of Local Hormonal Treatment for Vulvovaginal Atrophy in Women With Estrogen Receptor-positive Breast Cancer Who Are on Adjuvant Aromatase Inhibitor Therapy: Meta-analysis." Clinical Breast Cancer 19(6): e731-e740.
	Atrophic vaginitis is a relatively common adverse effect of aromatase inhibitors used as an adjunctive treatment for breast cancer. Vaginal estrogen therapy is a treatment option, but the safety of its use in estrogen receptor-positive breast cancer remains understudied. The aim of our study was to determine the safety of local hormonal treatment of vulvovaginal atrophy in women treated with aromatase inhibitors. Our meta-analysis was based on a systematic search of the literature and selection of high-quality evidence. The safety of local hormonal therapy of vaginal atrophy in women on aromatase inhibitors were summarized using calculators built by the authors; heterogeneity was assessed by the Cochrane Q test and I 2 values. Several types of bias were assessed; publication bias was calculated by a funnel plot and the Egger regression. Eleven studies fulfilled the inclusion criteria for our study. After 8 weeks of local hormonal treatment, there was no change in the serum levels of luteinizing hormone and estradiol, whereas sex hormone binding globulins were low, and follicle stimulating hormone was almost doubled compared with the baseline. Adverse effect rates of vaginal discharge, facial hair growth, urinary tract or yeast infection, and vaginal or vulvar itching and/or irritation did not show significant changes in the sensitivity analysis, with exception of a single trial. Current evidence suggests that vaginal estrogen administration in postmenopausal women with a history of breast cancer is not associated with systemic absorption of sex hormones and may provide indirect evidence for the safety of their use. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pavone, M., et al. (2024). "Therapeutic role of para-aortic lymphadenectomy in patients with intermediate- and high-risk endometrial cancer: a systematic review and meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Objective: Lymph nodal involvement is a prognostic factor in endometrial cancer. The added value of para-aortic lymphadenectomy compared with pelvic nodal evaluation alone remains a matter of debate in the management of patients with intermediate- and high-risk endometrial cancer. A systematic review and meta-analysis was conducted to assess the prognostic value of para-aortic lymphadenectomy in terms of overall survival and disease-free survival in patients with intermediate- and high-risk endometrial cancer.; Methods: The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched from January 2000 to April 2023. Studies on intermediate- and high-risk patients who underwent pelvic versus pelvic and para-aortic dissection were included in the analysis. The Methodological Index for Nonrandomized Studies (MINORS) and the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) were used for quality assessment of the selected articles.; Results: Fourteen studies were identified, encompassing 9415 patients with a median age of 62 years (IQR 56.5-66.5). The majority had International Federation of Gynecology and Obstetrics stage I-II disease (76%) and endometrioid histology (89%). The 72% of patients who underwent only pelvic nodal evaluation and the 87% who underwent pelvic and para-aortic lymphadenectomy received adjuvant treatment (p=0.44). Pelvic and para-aortic lymphadenectomy was associated with a significant improvement in 5-year overall survival (RR=0.71, 95% CI 0.57 to 0.88, p<0.01), translating to a 41% reduction in the risk of overall death. However, no significant differences were observed in the 5-year risk of recurrence (RR=1.12, 95% CI 0.94 to 1.34, p=0.15). Additionally, patients undergoing pelvic and para-aortic lymphadenectomy experienced a 26% increased risk of post-operative complications (RR=1.26, 95% CI 1.04 to 1.53, p=0.03) and prolonged operative times (MD=56.27, 95% CI 15.94 to 96.60, p<0.01).; Conclusion: Pelvic and para-aortic lymphadenectomy appears to confer a prognostic benefit in patients with intermediate- and high-risk endometrial cancer. Robust prospective studies are needed to further validate these findings and elucidate the precise role of para-aortic lymphadenectomy in the optimal management of these patients.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Pawalia, A., et al. (2022). "Can taping reduce menstrual pain, distress, and anxiety? A systematic review and meta-analysis." Advances in Rehabilitation 36(3): 49-59.
	Nowadays, Primary dysmenorrhea (PD) is a common problem with varying degree of symptoms in women. The present study is aimed to provide evidence for effect of taping on pain and related symptoms of primary dysmenorrhea such as menstrual distress and anxiety, along with effect of duration of given intervention on pain. The electronic databases such as PubMed and Cochrane library were searched from inception to February 2021, using appropriate keywords related to the study condition and outcome measures. Eight studies were selected for review based on the inclusion and exclusion criteria of the study. The methodological quality and risk of bias was assessed by "Physiotherapy Evidence Database (PEDro) scale" and Cochrane collaboration tool for risk of bias assessment, respectively. The findings from their analysis suggested that taping was significantly reducing pain (p = 0.0004), menstrual distress (p = 0.02) and anxiety level (p < 0.00001) in individual who received taping when compared to the individuals who did not received taping as an intervention. In addition, subgroup analysis based on total duration of taping intervention revealed that short-term taping (<1 month) was significantly effective (p < 0.00001) in reducing pain as compared to long-term taping (>1 month) (p = 0.12). The study concluded that taping can be used as an effective short-term treatment method to reduce pain, menstrual distress and anxiety level among individuals with primary dysmenorrhea.Copyright © 2022 Korean Neurotraumatology Society.

Paz, F., et al. (2021). "Effects of exercise in pregnant and postpartum depression. A systematic review." Clinica e Investigacion en Ginecologia y Obstetricia 48(4): 100683.
	The aim of this paper is to evaluate the current scientific literature on the effects of exercise on depression during pregnancy and postpartum. A search was conducted in the Medline, Web of Science and Scopus databases using the MeSH terms "depression", "pregnancy", "postpartum" and "exercise". Fifteen studies were analysed in which the most commonly used intervention protocol was supervised structured aerobic exercise, strength, stretching, relaxation, and pelvic floor exercise. Non-regulated physical activity based on activities of daily living such as walking was also applied. Significant improvements were observed in variables indicative of depression and other factors of psychological well-being. Therefore, exercise has been shown to be a valid method to improve depression during pregnancy and postpartum. The findings in this work could represent a further method of treatment for depression during these stages., El objetivo de este trabajo es compilar la literatura cientifica actual sobre los efectos del ejercicio en la depresion durante el embarazo y el posparto. Se realizo una busqueda en las bases de datos Medline, Web of Science y Scopus, utilizando los terminos MeSH <>, < >, < > y <>. Se analizaron 15 estudios en los que el protocolo de intervencion mas utilizado fue el ejercicio estructurado supervisado de naturaleza aerobico, de fuerza, estiramientos, de relajacion y de suelo pelvico. Tambien se aplico actividad fisica no reglada basada en actividades de la vida diaria como caminar. Se observaron mejoras significativas en las variables indicativas de depresion y otros factores de bienestar psicologico. Por lo tanto, el ejercicio ha demostrado ser un metodo valido para mejorar la depresion durante el embarazo y el posparto. Los hallazgos en este trabajo podrian suponer un metodo mas de tratamiento en la depresion durante estas etapas.Copyright © 2021 Elsevier Espana, S.L.U.

Pazhohan, A., et al. (2021). "The modulating effects of vitamin D on the activity of β-catenin in the endometrium of women with endometriosis: a randomized exploratory trial." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(3): 278-282.
	AIMS: The aim of this prospective study was to investigate the effects of vitamin D on the expression and activity of β-catenin, as the key molecule of the Wnt/β-catenin signaling pathway, in endometriosis women. MATERIALS AND METHODS: Thirty four infertile women with stage III or IV endometriosis were randomly divided to two groups. The control group received the routine treatment and the treatment group, beside the routine protocol, received 50000 IU vitamin D weekly for 12-14 weeks. Blood and endometrial tissue were collected from both groups before and after the intervention. Protein and Gene expression levels of β-catenin were assessed by Western blotting and Real-Time PCR, respectively. RESULTS: Compared to before intervention, the expression of active form of β-catenin reduced significantly within treatment group (p = .000), in addition, the difference between control and treatment groups (p = .012) was significant after intervention, too. Also, the ratio of active/total form of β-catenin protein expression was significantly decreased within the treatment group at the end of intervention period (p = .000). CONCLUSIONS: It seems vitamin D can change the activity of β-catenin protein in the endometrial cells of endometriosis patients. Further studies on the therapeutic potential of vitamin D in modifying the β-catenin activity in endometriosis patients are warranted. CLINICAL TRIAL REGISTRATION NUMBER: IRCT2015081823678N1. TRIAL REGISTRATION DATE: 29 September 2015.

Pearce, E., et al. (2020). "Exercise for premenstrual syndrome: A systematic review and meta-analysis of randomised controlled trials." BJGP Open 4(3): bjgpopen20X101032.
	Background: Exercise is recommended as a treatment for premenstrual syndrome (PMS) in clinical guidelines, but this is currently based on poor-quality trial evidence. Aim(s): To systematically review the evidence for the effectiveness of exercise as a treatment for PMS. Design & setting: This systematic review searched eight major databases, including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), and two trial registries from inception until April 2019. Method(s): Randomised controlled trials (RCTs) comparing exercise interventions of a minimum of 8-weeks duration with non-exercise comparator groups in women with PMS were included. Mean change scores for any continuous PMS outcome measure were extracted from eligible trials and standardised mean differences (SMDs) were calculated where possible. Random-effects meta-analysis of the effect of exercise on global PMS symptoms was the primary outcome. Secondary analyses examined the effects of exercise on predetermined clusters of psychological, physical, and behavioural symptoms. Result(s): A total of 436 non-duplicate returns were screened, with 15 RCTs eligible for inclusion (n = 717). Seven trials contributed data to the primary outcome meta-analysis (n = 265); participants randomised to an exercise intervention reported reduced global PMS symptom scores (SMD = -1.08; 95% confidence interval [CI] = -1.88 to -0.29) versus comparator, but with substantial heterogeneity (I2 = 87%). Secondary results for psychological (SMD = -1.67; 95% CI = -2.38 to -0.96), physical (SMD = -1.62; 95% CI = -2.41 to -0.83) and behavioural (SMD = -1.94; 95% CI = -2.45 to -1.44) symptom groupings displayed similar findings. Most trials (87%) were considered at high risk of bias. Conclusion(s): Based on current evidence, exercise may be an effective treatment for PMS, but some uncertainty remains.Copyright © 2020, The Authors.

Pearson, S., et al. (2022). "Community-based Versus Traditional Research Among Older Minority Women With Urinary Incontinence." Female Pelvic Medicine and Reconstructive Surgery 28(4): 201-206.
	Objective The aim of this study was to evaluate research retention of older minority women with urinary incontinence (UI) using a community-based participatory research (CBPR) versus a traditional research approach. Methods An ancillary prospective study was conducted within an ongoing pilot randomized clinical trial to treat UI. Participants were recruited using CBPR in collaboration with a local community versus a traditional research approach at an academic center. Inclusion criteria were women 65 years and older and symptomatic UI. The primary outcome was the randomization rate defined as the proportion of women randomized into the randomized clinical trial out of screened participants. Screening and consent rates were also evaluated. Pearson chi2, Fisher exact, and t tests were used. The effect of CBPR on research retention rates was expressed as odds ratio (OR) with 95% confidence intervals (CI). Results There were 10 and 88 women screened in the CBPR and traditional research groups, respectively. The CBPR participants were Hispanic (n = 10, 100%) and older (78.4 +/- 8.3 years; P < 0.01). Most of the traditional research participants were non-Hispanic Black (n = 55, 62.5%) and younger (71.0 +/- 4.9 years). The CBPR group had higher rates of screening (76.9% vs 40.6%; P = 0.01), consent (80% vs 44.3%; P = 0.045), and randomization (50.0% vs 14.8%; P < 0.01) compared with the traditional research group. Community-based participatory research increased the odds of research retention during screening (OR, 4.9; 95% CI, 1.3-18.2), consent (OR, 5.0; 95% CI, 1.0-25.0), and randomization (OR, 5.8; 95% CI, 1.5-22.7). Conclusion Compared with traditional research, CBPR yielded higher research retention among older minority women with UI in a clinical study.Copyright © American Urogynecologic Society. All rights reserved.

Pedro, M., et al. (2021). "Immunological therapies in women undergoing assisted conception: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Pehlivan Melissa, J., et al. (2023). "The effectiveness of psychological interventions for reducing poor body image in endometriosis, PCOS and other gynaecological conditions: a systematic review and meta-analysis." Health psychology review: 1-28.
	Gynaecological conditions (e.g., endometriosis, PCOS) result in bodily changes that negatively impact body image. Psychological interventions (e.g., CBT, psychoeducation) have shown promise in reviews with the general population for alleviating body image concerns. This systematic review and meta-analysis aims to provide asynthesis of the impact of psychological interventions for reducing body image concerns for individuals with gynaecological conditions. Electronic databases were searched for relevant psychological intervention studies with body image outcomes. Twenty-one eligible studies were included in the systematic review (ten were included in a random-effects meta-analysis). Studies included participants ( N = 1483, M = 71.85, SD = 52.79) with a range of gynaecological conditions, ages ( M age = 35.08, SD = 12.17) and cultural backgrounds. Most included studies reported at least one positive effect with the meta-analysis indicating psychological interventions were moderately superior to control conditions for reducing body image concerns (SMD -.41, 95% CI [-0.20 -0.62]). However, there was a high risk of bias and moderate heterogeneity. Results suggest psychological interventions may hold promise for reducing body image concerns among individuals gynaecological conditions in the short term. Further, preliminary support was found for the use of theory-guided psychological interventions delivered in group settings in particular, with further research needed on optimal intervention length and particular psychotherapeutic approach.

Pei, J., et al. (2023). "Impact of human papillomavirus vaccine on cervical cancer epidemic: Evidence from the surveillance, epidemiology, and end results program." Frontiers in Public Health 10: 998174.
	Introduction: Since 2006, the human papillomavirus (HPV) vaccine has been recommended for females aged 9-26 years in the United States. Aiming to evaluate the early effect of the HPV vaccine on cervical cancer, this study assessed the incidence of cervical cancer by age and histology before and after the introduction of HPV vaccination.; Methods: Data on cervical cancer incidence from 1975-2019 were extracted from the Surveillance, Epidemiology, and End Results Program. Joinpoint regression was used to determine temporal trends over time. Future cervical cancer incidence (2015-2039) was projected using Bayesian age-period-cohort analysis. Age-period-cohort (APC) models were created to evaluate age, period, and cohort effects.; Results: For overall cervical cancer and cervical squamous cell carcinoma (SCC), incidence rate showed decreasing trends (-0.7%, and -1.0% annually, respectively), whereas cervical adenocarcinoma (AC) incidence continuously increased (2.6% annually). The incidence trends for AC were stable in the 20-24 and 25-29-year age groups, whereas there was an increasing trend in older age groups. Similarly, the projected trend for AC in females aged 20-30 years exhibited a decline, whereas an increase was predicted in the 31-40-year age group, especially in the 35-44 year age group. The birth cohort and period effects in SCC and AC were extracted from APC models.; Discussion: During the period of 1975-2019, the incidence of cervical AC remained almost unchanged in the age groups receiving HPV vaccines while increased in the age groups not receiving HPV vaccines. The birth cohort effects of SCC and AC of the cervix provided evidence supporting the effectiveness of the HPV vaccine in preventing cervical cancer.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Pei, Shu, Wu, Li, Xu, Jiang and Zhu.)

Pei, Y., et al. (2022). "Efficacy and Safety of Platinum-Based Chemotherapy for Ovarian Cancer During Pregnancy: A Systematic Review and Meta-Analysis." Oncology and therapy 10(1): 55-73.
	Introduction: Based on the available data on ovarian cancer during pregnancy, we performed a review and meta-analysis to evaluate the efficacy and safety of platinum-based chemotherapy against ovarian cancer during pregnancy.; Methods: We systematically searched three databases including the PubMed, Embase, and Cochrane Library databases for articles published from January 1986 to December 2020 using the following terms: "ovarian tumors OR ovarian carcinoma OR adnexal masses OR ovarian cancer" AND "pregnancy" AND "chemotherapy." Two authors (Yaping Pei and Yuanfeng Gou) independently searched the literature and extracted data from each eligible study. The outcome measures were overall survival (OS) and progression-free survival (PFS). The OS and PFS of all patients were estimated by Kaplan-Meier survival curves and log-rank tests.; Results: A total of 43 studies including 55 cases of ovarian cancer during pregnancy were selected. Forty-eight patients were comprehensively staged using the International Federation of Gynecology and Obstetrics (FIGO) staging system. Twenty-six of the 48 patients (54.17%) were diagnosed with early-stage disease, while the remaining had advanced stages (II, III, and IV). The mean age at diagnosis was 29.31 years. The majority of patients in this meta-analysis were diagnosed at a mean gestational age of 16.05 weeks. The mean GA at chemotherapy administration was 17.42 weeks. Overall, 55 women gave birth to 56 newborns, including a pair of twins. At the end of follow-up (median 10 months, range 0-73 months), all the children were healthy, except for one child who died 5 days after delivery due to a congenital abnormality. During 2-204 months of follow-up, there were five cases of recurrence, with no evidence of recurrence in the remaining cases. Unfortunately, one patient died 29 months after diagnosis. Neither median overall survival nor median progression-free survival was obtained.; Conclusion: Platinum-based chemotherapy may be a good choice for pregnant women with ovarian cancer who want to continue their pregnancy. (© 2021. The Author(s).)

Pei, Y., et al. (2023). "Beneficial effects of pioglitazone and alpha-lipoic acid in patients with polycystic ovaries syndrome." European Review for Medical and Pharmacological Sciences 27(15): 7118-7126.
	OBJECTIVE: Changes in hormone levels, improper lipid metabolism, and oxidative stress all significantly contribute to the pathogenic process of polycystic ovarian syndrome (PCOS). According to earlier research, pioglitazone and alpha-lipoic acid are crucial in the emergence of PCOS. The beneficial effects of pioglitazone and alpha-lipoic acid on PCOS were examined in the current study. PATIENTS AND METHODS: The 120 patients with PCOS received three months of treatment in pioglitazone groups (n=40 case, 30 mg/time, 1 time/day), alpha-lipoic acid (n=40 case, 0.6 g/time, 1 time/day), and combination therapy (n=40 case, pioglitazone 30 mg/time, 1 time/day and alpha-lipoic acid, 0.6 g/time, 1 time/day). Before and after therapy, the following factors were evaluated: the hormonal profile, fasting serum insulin, body weight, body mass index (BMI), menstruation status, oxidative stress, and indications of lipid metabolism. RESULT(S): The combination of pioglitazone and alpha-lipoic acid has a significantly improving effect on BMI, body weight, oxidative stress levels, lipid metabolism, and menstrual status. A significant increase in body weight, BMI, and follicle-stimulating hormone (FSH) levels were found in mice after being treated with alpha-lipoic acid alone. However, the use pioglitazone alone improves body weight, BMI, the calculation of insulin resistance index (HOMA-IR), Area under the curve (AUC)-insulin, fasting glucose/insulin (G/I) ratio, total testosterone, and malondialdehyde (MDA) levels in post-treatment than pre-treatment. CONCLUSION(S): These findings suggest that pioglitazone alone has a better effect than alpha-lipoic acid in improving oxidative stress levels, BMI, and menstrual cyclicity. Additionally, treatment with pioglitazone and alpha-lipoic acid did demonstrate a greater effect than mono-therapy with each medication alone.Copyright © 2023 Verduci Editore s.r.l. All rights reserved.

Pei, Y., et al. (2023). "Beneficial effects of pioglitazone and α-lipoic acid in patients with polycystic ovaries syndrome." European Review for Medical and Pharmacological Sciences 27(15): 7118-7126.
	Objective: Changes in hormone levels, improper lipid metabolism, and oxidative stress all significantly contribute to the pathogenic process of polycystic ovarian syndrome (PCOS). According to earlier research, pioglitazone and alpha-lipoic acid are crucial in the emergence of PCOS. The beneficial effects of pioglitazone and alpha-lipoic acid on PCOS were examined in the current study.; Patients and Methods: The 120 patients with PCOS received three months of treatment in pioglitazone groups (n=40 case, 30 mg/time, 1 time/day), α-lipoic acid (n=40 case, 0.6 g/time, 1 time/day), and combination therapy (n=40 case, pioglitazone 30 mg/time, 1 time/day and α-lipoic acid, 0.6 g/time, 1 time/day). Before and after therapy, the following factors were evaluated: the hormonal profile, fasting serum insulin, body weight, body mass index (BMI), menstruation status, oxidative stress, and indications of lipid metabolism.; Results: The combination of pioglitazone and α-lipoic acid has a significantly improving effect on BMI, body weight, oxidative stress levels, lipid metabolism, and menstrual status. A significant increase in body weight, BMI, and follicle-stimulating hormone (FSH) levels were found in mice after being treated with α-lipoic acid alone. However, the use pioglitazone alone improves body weight, BMI, the calculation of insulin resistance index (HOMA-IR), Area under the curve (AUC)-insulin, fasting glucose/insulin (G/I) ratio, total testosterone, and malondialdehyde (MDA) levels in post-treatment than pre-treatment.; Conclusions: These findings suggest that pioglitazone alone has a better effect than alpha-lipoic acid in improving oxidative stress levels, BMI, and menstrual cyclicity. Additionally, treatment with pioglitazone and alpha-lipoic acid did demonstrate a greater effect than monotherapy with each medication alone.

Peila, R., et al. (2023). "Menopausal hormone therapy and change in physical activity in the Women's Health Initiative hormone therapy clinical trials." Menopause (New York, N.Y.) 30(9): 898-905.
	Objective: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women.; Methods: A total of 27,327 postmenopausal women aged 50-79 years enrolled in the Women's Health Initiative randomized double-blind trials of menopausal hormone therapy. Self-reported leisure-time physical activity at baseline, and years 1, 3, and 6 was quantified as metabolic equivalents (MET)-h/wk. In each trial, comparison between intervention and placebo groups of changes in physical activity levels from baseline to follow-up assessment was examined using linear regression models.; Results: In the CEE-alone trial, the increase in MET-h/wk was greater in the placebo group compared with the intervention group at years 3 ( P = 0.002) and 6 ( P < 0.001). Similar results were observed when analyses were restricted to women who maintained an adherence rate ≥80% during the trial or who were physically active at baseline. In the CEE + MPA trial, the primary analyses did not show significant differences between groups, but the increase of MET-h/wk was greater in the placebo group compared with the intervention group at year 3 ( P = 0.004) among women with an adherence rate ≥80%.; Conclusions: The results from this clinical trial do not support the hypothesis that estrogen treatment increases physical activity among postmenopausal women.; Competing Interests: Conflict of interest/financial disclosures: R.T.C. receives ongoing funding from UpToDate . M.S.L. received $1000 honorarium from the New England Bone Club for a plenary lecture at the 2022 New England Bone Club meeting. The other authors have nothing to disclose. (Copyright © 2023 by The North American Menopause Society.)

Peipert John, D., et al. (2023). "Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial." Gynecologic Oncology 175: 1-7.
	Purpose: To compare NFOSI-18 Disease Related Symptoms - Physical (DRSP), Total score, and side effect bother between maintenance rucaparib (600 mg twice daily) vs. placebo in the phase III ARIEL3 trial.; Methods: ARIEL3 (NCT01968213) included patients with ovarian carcinoma who responded to second-line or later platinum-based chemotherapy. The NFOSI-18 DRS-P and Total scales were secondary endpoints. The NFOSI-18 contains a side effect impact item (GP5): "I am bothered by side effects of treatment." We compared treatment arms on change from baseline of DRS-P and Total scores using mixed models with repeated measures (MRMM). Time to first and confirmed deterioration of NFOSI-18 DRS-P and Total scales were analyzed using Cox regression. We also calculated the proportion of patients reporting moderate to high side effect bother on GP5.; Results: In the intention-to-treat (ITT) cohort, mean change from baseline favored the placebo. Compared to placebo, rucaparib was associated with higher risk of deterioration [e.g., 4-point deteriorator definition hazard ratio (HR): 1.85; 95% CI: 1.46, 2.36; median time to first deterioration on DRSP: 1.9 vs. 7.0 months]. Confirmed deterioration results resembled those for first deterioration. Proportions of patients reporting moderate/high side effect bother on GP5 fluctuated around 20% across treatment cycles. Results in BRCA mutant and homologous recombination deficient cohorts were generally similar to those from the ITT cohort.; Conclusion: This placebo-controlled study in the maintenance therapy setting provides a unique view of the impact of PARP inhibition on the patient-reported outcomes that are commonly used in ovarian cancer clinical trials. Information regarding the adverse side effect impact of PARP inhibitors should be weighed against their clinical benefit. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Peishuang, L., et al. (2021). "Effects of Acupuncture Combined with Moxibustion on Reproduction and Hormone Outcomes for Polycystic Ovary Syndrome: A Systematic Review." PROSPERO International prospective register of systematic reviews.
	
Peitsidis, N., et al. (2023). "Diagnostic hysteroscopy with endometrial fundal incision may improve reproductive outcomes in oocyte recipients after implantation failure." JBRA Assisted Reproduction.
	Objective: This study aimed to investigate whether hysteroscopy plus endometrial fundal incision (EFI) with endoscopic scissors can improve reproductive outcomes in oocyte recipients who have failed in their first egg donation cycle.; Methods: This was a prospective study (2014-2022) conducted in Assisting Nature Centre Reproduction and Genetics, Thessaloniki Greece, IVF Unit. The study population consisted of oocyte recipients with implantation failure in their first embryo transfer (ET) with donor eggs. All the recipients underwent routine evaluation during their early follicular phase, 1-3 months before the start of a new cycle with donor oocytes and were eligible to undergo EFI.; Results: During the study period, 218 egg recipients underwent egg donation; 126 out of 218 oocyte recipients (57.8%) did not achieve a live birth at the 1st ET. 109 of them had surplus embryos cryopreserved and underwent a second ET; 50 women consented for EFI. Both groups were similar in terms of age, years of infertility, duration of estrogen replacement protocol and number of transferred blastocysts (p>0.05). In the EFI group, 60% had normal intrauterine cavity, while 40% had minor anomalies. The pregnancy test was positive in 46% (n=23/50) in the EFI group compared with 27.1% (n=16/59) in the control group (p=0.04). Moreover, live birth rates were higher in the EFI group compared to the control group (38.0% vs. 20.3%; p=0.04).; Conclusions: The findings of our study indicate that in oocyte recipients after implantation failure, diagnostic hysteroscopy plus EFI prior to subsequent ETmay increase pregnancy and live birth rates.

Peiwen, L. and W. Yizi (2023). "Protective effectiveness of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer." PROSPERO International prospective register of systematic reviews.
	
Pelazas-Hernández Jesus, A., et al. (2023). "The Effect of Virtual Reality on the Reduction of Pain in Women with an Indication for Outpatient Diagnostic Hysteroscopy: A Randomized Controlled Trial." Journal of Clinical Medicine 12(11).
	Background: The cognitive distraction caused by Virtual Reality (VR) seems to cause a decrease both in pain and its perception as in the time spent thinking about possible pain, among anxiety about hysteroscopy procedure. The main objective of this investigation was to evaluate the efficacy of virtual reality for pain relief during outpatient hysteroscopy. Method : A total of 83 patients underwent outpatient diagnostic hysteroscopy in a single-centre, open-label, randomized control trial. Overall, 180 women with medical indication for an outpatient diagnostic hysteroscopy were randomized. Ten were excluded due to the impossibility of entering the endometrial cavity caused by a cervical canal that was not permeable, and 15 did not tolerate the pain at the beginning and during the procedure, excluding themselves from the final model. Finally, 154 were analysed per protocol to use VR ( n = 82, study group) or standard treatment ( n = 72, control group) assessing the differences between both groups by reduction in pain using Visual Analogue Scale score (VAS: 0-10 cm) and clinical data (arterial pressure, heart rate, and oxygen saturation) at the end of hysteroscopy, at 15 and 30 min after hysteroscopy. Results : Women with VR outpatient diagnostic hysteroscopy experienced less pain at final (VAS score 2.451 vs. 3.972, standard mean difference (SMD) -1.521, 95% CI -2.601 to -0.440; p = 0.006), at 15 min (VAS 1.769 vs. 3.300, SMD -1.531, 95% CI -2.557 to -0.504; p = 0.004), and at 30 min (VAS 1.621 vs. 2.719, SMD -1.099, 95% CI -2.166 to -0.031; p = 0.044) after the ending of the hysteroscopy, compared with no VR. Conclusions : The use of VR during outpatient diagnostic hysteroscopy proved effective in the reduction of pain in this randomized control trial. It shows wide potential role in ambulatory gynaecologic procedures to avoid repeating tests, perform surgeries without anaesthesia, and the use of medication and its side effects.

Pelex (2023). Comparison of Virtual Pelvic Floor Physical Therapy With a Pelvic Floor Trainer in the Treatment of Stress Urinary Incontinence.
	No Results Available Device: Pelex Upp|Behavioral: Pelvic Floor Physical Therapy Change in stress urinary incontinence symptoms Female Not Applicable 45 Industry Allocation: Randomized|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment PLX-002 January 31, 2024

Pellino, G., et al. (2022). "Abdominal versus perineal approach for external rectal prolapse: systematic review with meta-analysis." BJS Open 6(2).
	Background: External rectal prolapse (ERP) is a debilitating condition in which surgery plays an important role. The aim of this study was to evaluate the outcomes of abdominal approaches (AA) and perineal approaches (PA) to ERP.; Methods: This was a PRISMA-compliant systematic review with meta-analysis. Studies published between 1990 and 2021 were retrieved. The primary endpoint was recurrence at the last available follow-up. Secondary endpoints included factors associated with recurrence and function. All studies were assessed for bias using the Newcastle-Ottawa Scale and Cochrane tool.; Results: Fifteen studies involving 1611 patients (AA = 817; PA = 794) treated for ERP were included, three of which were randomized controlled trials (RCTs; 114 patients (AA = 54; PA = 60)). Duration of follow-up ranged from 12 to 82 months. Recurrence in non-randomized studies was 7.7 per cent in AA versus 20.1 per cent in PA (odds ratio (OR) 0.29, 95 per cent confidence interval (c.i.) 0.17 to 0.50; P < 0.001, I2 = 45 per cent). In RCTs, there was no significant difference (9.8 per cent versus 16.3 per cent, AA versus PA (OR 0.82, 95 per cent c.i. 0.29 to 2.37; P = 0.72, I2 = 0.0 per cent)). Age at surgery and duration of follow-up were risk factors for recurrence. Following AA, the recurrence rates were 10.1 per cent and 6.2 per cent in patients aged 65 years and older and less than 65 years of age, respectively (effect size [e.s.] 7.7, 95 per cent c.i. 4.5 to 11.5). Following PA, rates were 27 per cent and 16.3 per cent (e.s. 20.1, 95 per cent c.i. 13 to 28.2). Extending follow-up to at least 40 months increased the likelihood of recurrence. The median duration of hospital stay was 4.9 days after PA versus 7.2 days after AA. Overall, incontinence was less likely after AA (OR 0.32), but constipation occurred more frequently (OR 1.68). Most studies were retrospective, and several outcomes from RCTs were not consistent with those observed in non-RCTs.; Conclusion: The overall risk of recurrence of ERP appears to be higher with PA versus AA. Incontinence is less frequent after AA but at the cost of increased constipation. Age at surgery and duration of follow-up are associated with increased risk of recurrence, which warrants adequate reporting of future studies on this topic. (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Pendergast, J., et al. (2021). Time-Restricted Feeding Intervention in Metabolically-Unhealthy Postmenopausal Women.
	No Results Available Behavioral: Time-Restricted Feeding (TRF) Change in Insulin Sensitivity|Change in Body Mass Index|Change in Triglycerides|Change in Hemoglobin A1c|Change in C-Reactive Protein|Change in Mid-sleep|Change in Sleep Fragmentation Index Female Not Applicable 164 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Prevention BIO-21-TRF|1R01DK124774-01A1 February 27, 2026

Peng, A., et al. (2019). "Natalizumab exposure during pregnancy in multiple sclerosis: a systematic review." Journal of the Neurological Sciences 396: 202-205.
	
Peng, C., et al. (2021). "Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis." Archives of Gynecology and Obstetrics 304(1): 231-252.
	Purpose: Endometriosis is a common, chronic gynecological disease that affects women's fertility potential. Dydrogesterone is an effective and safe drug that is under-utilized due to limited clinical research. The purpose of this evidence mapping is to identify, describe, and analyze the current available evidence regarding dydrogesterone for the treatment of endometriosis.; Materials and Methods: We performed a search in electronic databases: Medline, The Cochrane Library, EMBASE, PubMed, CNKI, Wanfang, VIP, and CBM. We also hand-searched google for relevant studies. Our primary outcomes included changes in pain relief including pelvic pain, dysmenorrhea, and dyspareunia. Secondary outcomes included pregnancy rate, frequency of analgesic use, and other reported outcomes according to specific settings in the studies.; Results: Of 377 references screened, 19 studies were included in the data synthesis involving 1709 female participants. Nearly three-quarters were either randomized control trials or clinical control trials. Compared with gestrinone, dydrogesterone relieved dysmenorrhea, increased the pregnancy rate, and reduced the risk of certain adverse events. Compared with GnRH-a, dydrogesterone also lowered the risk of endometriosis recurrence and elevated transaminase levels. Whether there was any difference in efficacy between dydrogesterone and leuprolide acetate, letrozole or traditional Chinese medicine remains unclear due to insufficient data.; Conclusions: The amount and quality of evidence evaluating the effects of dydrogesterone for the treatment of endometriosis is generally very low. Limited evidence suggests that dydrogesterone may have some advantages over gestrinone, GnRH agonists, and other therapeutic interventions in treating endometriosis. However, this conclusion should be interpreted with caution.

Peng, G., et al. (2023). "The effects of first-line pharmacological treatments for reproductive outcomes in infertile women with PCOS: a systematic review and network meta-analysis." Reproductive biology and endocrinology : RB&E 21(1): 24.
	Background: Polycystic ovarian syndrome (PCOS) is one of the most common causes of infertility in reproductive-age women. However, the efficacy and optimal therapeutic strategy for reproductive outcomes are still under debate. We conducted a systematic review and network meta-analysis to compare the efficacy of different first-line pharmacological therapies in terms of reproductive outcomes for women with PCOS and infertility.; Methods: A systematic retrieval of databases was conducted, and randomized clinical trials (RCTs) of pharmacological interventions for infertile PCOS women were included. The primary outcomes were clinical pregnancy and live birth, and the secondary outcomes were miscarriage, ectopic pregnancy and multiple pregnancy. A network meta-analysis based on a Bayesian model was performed to compare the effects of the pharmacological strategies.; Results: A total of 27 RCTs with 12 interventions were included, and all therapies tended to increase clinical pregnancy, especially pioglitazone (PIO) (log OR 3.14, 95% CI 1.56 ~ 4.70, moderate confidence), clomiphene citrate (CC) + exenatide (EXE) (2.96, 1.07 ~ 4.82, moderate confidence) and CC + metformin (MET) + PIO (2.82, 0.99 ~ 4.60, moderate confidence). Moreover, CC + MET + PIO (2.8, -0.25 ~ 6.06, very low confidence) could increase live birth most when compared to placebo, even without a significant difference. For secondary outcomes, PIO showed a tendency to increase miscarriage (1.44, -1.69 ~ 5.28, very low confidence). MET (-11.25, -33.7 ~ 0.57, low confidence) and LZ + MET (-10.44, -59.56 ~ 42.11, very low confidence) were beneficial for decreasing ectopic pregnancy. MET (0.07, -4.26 ~ 4.34, low confidence) showed a neutral effect in multiple pregnancy. Subgroup analysis demonstrated no significant difference between these medications and placebo in obese participants.; Conclusions: Most first-line pharmacological treatments were effective in improving clinical pregnancy. CC + MET + PIO should be recommended as the optimal therapeutic strategy to improve pregnancy outcomes. However, none of the above treatments had a beneficial effect on clinical pregnancy in obese PCOS.; Trial Registration: CRD42020183541; 05 July 2020. (© 2023. The Author(s).)

Peng, J., et al. (2021). "Enhanced Recovery After Surgery Impact on the Systemic Inflammatory Response of Patients Following Gynecological Oncology Surgery: A Prospective Randomized Study." Cancer Management and Research 13: 4383-4392.
	OBJECTIVE: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body's response to surgical stress. METHODS: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints. RESULTS: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups. CONCLUSION: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT03629626).

Peng, J., et al. (2020). "[Efficacy of black cohosh extracts for improving low estrogen status induced by postoperative GnRHa treatment in patients with endometriosis: a systematic review]." Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 49(3): 397-405.
	Objective: To evaluate the efficacy of black cohosh extracts (BCE) in improving the low estrogen status induced by postoperative gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis.; Methods: Randomized clinical controlled trial about the improvement of low estrogen status caused by GnRHa with the treatment of BCE in patients with endometriosis after laparoscopic surgery were retrieved from Medline (Ovid), PubMed, Cochrane Library, CNKI, CBMdisc, Wanfang and VIP databases before January 2020, and meta-analysis of included studies was performed by Revman 5.3 software.; Results: Seven randomized controlled trials involving 745 patients were included in this study. Meta-analysis results showed that the addition of BCE did not alter hormone levels of patients, including serum estradiol levels [ MD =1.24, 95% CI (-4.58, 7.08), P &gt;0.05] and luteinizing hormone levels [ MD =-0.02, 95% CI (-0.15, 0.11), P &gt;0.05]. BCE effectively improved the perimenopausal symptoms induced by low estrogen status:improving hectic fever and sweating [ OR =0.1, 95% CI (0.02, 0.47), P &lt; 0.01], reducing the occurrence of insomnia symptoms [ OR =0.23, 95% CI (0.13, 0.39), P &lt; 0.01], improving fatigue [ OR =0.09, 95% CI (0.04, 0.20), P &lt; 0.01], reducing the occurrence of vaginal dryness [ OR =0.04, 95% CI (0.01, 0.30), P &lt; 0.01]. BCE affected Kupperman's menopausal index (KMI) score 12 weeks after the surgery [ MD =-11.50, 95% CI (-20.09, -2.90), P &lt; 0.01] and KMI score 24 weeks after the surgery [ MD =-23.68, 95% CI (-39.66, -7.69), P &lt; 0.01].; Conclusions: The limited evidence so far indicates that BCE could efficiently improve perimenopausal symptoms cause by low estrogen status of the patients recieved GnRHa treatment after surgery for endometriosis, but does not alter hormone levels of patients.

Peng, L., et al. (2020). "Effects of repetitive transcranial magnetic stimulation on depression symptoms and cognitive function in treating patients with postpartum depression: A systematic review and meta-analysis of randomized controlled trials." Psychiatry Research 290: 113124.
	Repetitive transcranial magnetic stimulation (rTMS) has been used to treat postpartum depression (PPD), but its effectiveness is still uncertain. To evaluate the effect of rTMS on depression symptoms and recognition function in patients with PPD, we systematically searched CNKI, WanFang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database from inception to June 2019 for randomized controlled trials (RCT) in English or Chinese concerning PPD in women treated with rTMS. Reference lists were also searched. RCT were included if they compared rTMS with no intervention or sham in patients with PPD. Related data was extracted and risk of bias was assessed by two investigators independently. Of 81 identified studies, 14 met our inclusion criteria (n=884 participants). Compared with control group, rTMS treatment yielded a reduction in Hamilton Depression Rating Scale score and Edinburgh Postnatal Depression Scale score, and improved the cognitive function of patients with PPD. Current evidence of RCT showed that rTMS could improve depression symptoms and cognitive function in patients with PPD.; Competing Interests: Declaration of Competing Interest The authors declared no conflicts of interest. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Peng, M. and L. Wenxun (2021). "Therapeutic efficacy of clomiphene citrate combined with metformin in patients with polycystic ovary syndrome: a meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Peng, R., et al. (2021). "Efficacy observation of misoprostol combined with superconducting visual painless abortion in primigravida with high risk factors of abortion." 中国实用医药 16(18): 120‐122.
	Objective: To investigate the clinical effect of misoprostol combined with superconducting visual and painless artificial abortion (abortion) in primigravida with high risk factors of abortion. Methods: 200 cases of primigravida with high risk factors of abortion were divided into observation group and control group according to different surgical methods, 100 cases in each. The observation group received misoprostol combined with superconducting visual painless abortion, while the control group received ordinary painless abortion. The composition of high‐risk abortion factors of the patients was analyzed, and the operation‐related conditions of the two groups were compared. Results: Among the 200 patients, 33 patients were ≤20 years old, 61 patients had extreme uterine inversion, 45 patients had uterine fibroids, 25 patients were pregnant with devices, 4 patients had mediastinum in the uterus, and those who had difficulty in cervical exposure. 28 cases, 4 cases of genital tract malformation, among which extreme uterus inversion, combined with uterine fibroids, and age ≤ 20 years accounted for 30.5%, 22.5%, and 16.5%, respectively, ranking the top 3. The effective rate of cervical relaxation in the observation group was 94% significantly higher than that in the control group (20%), the operation time (3.19±1.34) min and the intraoperative blood loss (8.12±2.81) ml were significantly lower than those in the control group (5.72±2.45) min, ( 12.90±4.17)ml, the difference was statistically significant (P<0.05). The incidence of abortion complications in the observation group was significantly lower than that in the control group by 12%, and the difference was statistically significant (χ^(2)=12.766, P=0.000<0.05). Conclusion: Misoprostol combined with superconducting visual painless abortion is safer and more effective than ordinary painless abortion in the treatment of primigravida with high‐risk factors of abortion, which is worthy of clinical promotion.

Peng, T., et al. (2021). "Acupuncture for chronic pelvic pain in patients with SPID: A protocol for systematic review and meta-analysis." Medicine 100(4): e23916.
	Background: Chronic pelvic pain (CPP) is one of the common sequela of pelvic inflammatory disease, the pathological factors are adhesions, scarring and pelvic congestion which caused by inflammation, often cause abdominal pain and lumbosacral soreness, and aggravated after fatigue, sexual intercourse and during menstruation. It is difficult to treat because special pathological changes. Although acupuncture has gained increased popularity for the management of CPP, evidence regarding its efficacy is lacking. Therefore, a systematic review of acupuncture for chronic pelvic pain in patients with SPID is required to provide available evidence for further study.; Methods and Analysis: We will conduct a systematic review of randomized controlled trials (RCTs) that investigate the effect and safety of acupuncture for the treatment of chronic pelvic pain patients with SPID. We will electronically search the literature in the databases of PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, the Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Digital Periodicals, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and select eligible articles. Data extraction will be conducted by 2 researchers independently, and risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcomes will be total effective rate and VAS pain score, and the secondary outcomes include the recurrence rate and adverse reaction. All data analysis will be conducted by software Review Manager V.5.3.; Results: This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture for chronic pelvic pain in patients with SPID.; Prospero Registration Number: CRD42020193826.; Competing Interests: The authors report no conflicts of interest. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Peng, W., et al. (2021). "Observation on the effect of different drug conservative treatment measures on patients with incomplete abortion." Chinese and foreign women's health research / 中外女性健康研究(18): 55‐56.
	Objective: To explore the effect of conservative treatment of different drugs on patients with incomplete abortion, in order to summarize the appropriate treatment drugs and methods, and benefit clinical practice. Methods: From August 2018 to December 2020, 300 patients with incomplete abortion who were admitted to the outpatient department of Shenzhen Longgang District Maternal and Child Health Hospital were selected and divided into three groups according to the random number table method, namely, group A took mifepristone, and group B took oral mifepristone. Estradiol Tablets/Estradiol Dydrogesterone Tablets and Wujia Biochemical Capsules were administered orally in group C, 100 cases in each group. The cure rate, vaginal bleeding time and menstrual rehydration time of the three groups of patients after treatment were recorded, and the pain visual analog scale (VAS) was used to evaluate the three groups of patients at 6h, 24h and 36h after treatment. Results: There was no significant difference in vaginal bleeding time, menstrual re‐emergence time and pain score among the three groups (P>0.05). There was no significant difference in the effective rate among the three groups (P>0.05); the incidence of complications, compared with group C, the incidence of complications in group A and group B increased significantly, and the difference was statistically significant (P<0.05). ). CONCLUSION: For patients with incomplete abortion, mifepristone, estradiol tablets/estradiol dydrogesterone tablets, and Wujia Biochemical Capsules have similar curative effects and similar pain improvement, but Wujia Biochemical Capsules have similar effects. Complications are few, and it is recommended that the clinical medication should be rationally administered according to the patient's symptoms.

Peng, Y., et al. (2022). "Meta analysis of the effect of phloroglucinol combined with progesterone in the treatment of threatened miscarriage before 20 weeks of gestation: a protocol for a systematic review." PROSPERO International prospective register of systematic reviews.
	
Peng, Z. and D. Minmin (2022). "Second curettage versus single curettage for preventing post-molar gestational trophoblastic neoplasia in patients with hydatidiform mole."
	
Peng, Z. and Z. Ying (2023). "Second curettage versus conventional chemotherapy in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses for patients with gestational trophoblastic neoplasia." PROSPERO International prospective register of systematic reviews.
	
Penn Courtney, A., et al. (2022). "Cost-effectiveness of hyperthermic intraperitoneal chemotherapy at primary cytoreduction of epithelial ovarian cancer based on residual disease status." Gynecologic Oncology Reports 41: 101009.
	Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin when used at the time of interval cytoreductive surgery (ICS) after neoadjuvant chemotherapy (NACT) has been shown to provide a survival advantage compared to interval cytoreduction alone for patients with advanced epithelial ovarian cancer in a cost-effective manner. A recent large multi-center retrospective cohort study showed a survival advantage with HIPEC given during primary debulking surgery compared to surgery alone. While there is an ongoing randomized controlled trial examining HIPEC at the time of primary cytoreductive surgery (PCS) before chemotherapy (OVHIPEC-2), there is currently no study of this practice in the United States or cost data to inform incorporation of this practice. To help guide the use of HIPEC in the upfront setting until the results of the OVHIPEC-2 are available in 2026, a decision-analytic cost-effectiveness model of the US healthcare sector was developed for patients undergoing PCS with or without HIPEC. Effectiveness inputs were extracted from a Chinese retrospective cohort study of 425 patients who underwent PCS with HIPEC and 159 patients who underwent PCS alone. We found incremental cost effectiveness ratios (ICER) of $9,789 per life year saved (LYS) for optimal PCS, $18,164/LYS for suboptimal PCS, and $7,854/LYS for all patients. Our findings provide preliminary data to support that HIPEC at the time of primary cytoreductive surgery can be considered cost-effective regardless of residual disease status when using a standard willingness to pay threshold.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors. Published by Elsevier Inc.)

Pennsylvania University, o. (2022). Post-partum Care in the NICU.
	No Results Available Other: Doula-coordinated, midwife-delivered postpartum care Time to receipt of postpartum care|Comparison of effectiveness of intervention for mothers with public vs private insurance|Comparison of effectiveness of intervention for mothers with infants less than 29 weeks gestational age vs those 29 weeks or older.|Receipt of Postpartum care Female Not Applicable 37 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 851606 September 2024

Pennsylvania University, o., et al. (2024). Improving Health Outcomes and Equity by Targeting Postpartum Mothers at Highest Risk.
	The goal of this educational clinical trial is to identify Black women most at risk for poor outcomes following delivery, the problems they experience, and to create a system to improve quality of postpartum care for high-risk women. The main question[s] it aims to answer are: How can the investigators help postpartum Black people who have poor outcomes by decreasing the number of ED visits/readmissions for postpartum people within the first 30 days postpartum? How can the investigators increase the ability of participants to "obtain needed services" and ability for patients to see their provider when they need to, in the 30-day post discharge period as one of the main pathways of unnecessary ED visits? Participants will be put into the study group or control group. The study group will receive a pamphlet postpartum with helpful information as well as a patient navigator who the participants will be able to reach out to their first 30 days postpartum.

Pennsylvania University, o., et al. (2023). Group Preconception Care for Fertility Patients.
	No Results Available Other: Group Preconception Care Blood pressure measurement recorded by clinician in Penn EMR|Weight measurement recorded by clinician in Penn EMR|Hemoglobin A1c testing results recorded in Penn EMR|Change in Anxiety screening score|Change in Depression screening score|Change in Fertility-related quality of life questionnaire score|Incidence of ovulation stimulations|Incidence of intrauterine inseminations|Incidence of in vitro fertilizations|Pregnancy rate|Time to pregnancy in days|Patient experience|Miscarriage rate|Number of pregnant participants with occurrence of a hypertensive disorder of pregnancy|Number of pregnant participants with a diagnosis of gestational diabetes|Number of pregnant participants with occurrences with an antepartum hospitalizations|Number of pregnant participants with preterm birth|Number of pregnant participants with a cesarean delivery|Number of pregnant participants with a NICU admission|Number of PEC (Perinatal Evaluation Center)/emergency room visits in pregnant participants|Among those patients that become pregnant, delivery length of stay|Among those patients that become pregnant, score on the Edinburgh Postnatal Depression Scale Female Not Applicable 140 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 852900 May 30, 2025

Pennycuff Jon, F., et al. (2022). "Commercially Available Home Pelvic Training Devices for the Treatment of Pelvic Floor Disorders: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 140(2): 275-292.
	Objective: To assess the clinical efficacy of commercially available pelvic muscle training devices on the treatment of pelvic floor disorders.; Data Sources: We searched MEDLINE, Web of Science, and ClinicalTrials.gov through April 2020. We included observational cohort studies and randomized trials. Case reports, case series, and conference poster presentations were excluded. Studies using vaginal weights or cones and those conducted in the peripartum periods were also excluded.; Tabulation, Integration, and Results: A total of 294 studies were screened. Twenty-six studies were included in the qualitative analysis, and 15 studies were eligible for meta-analyses. Study characteristics and quality were recorded for each study. Meta-analysis showed a large positive effect of commercially available pelvic floor training devices on pelvic floor muscle strength by both objective and subjective measures. Meta-analysis of objective measures showed a reduction of 1.2 pads per day (P<.01), 1.3 incontinence episodes per day, (P<.01) and 11 g on 24-hour pad test (P<.01). Meta-analysis of subjective measures showed a reduction in UDI-6 (Urogenital Distress Inventory, Short Form) scores by 25.1 points (P<.01) and in IIQ-7 scores (Incontinence Impact Questionnaire, Short Form) by 14.1 points (P=.01). There was an increase in I-QOL (Incontinence Quality of Life) scores by 16.8 points (P<.01). The minimal important difference was met for the UDI-6 and I-QOL but not for the IIQ-7. We were unable to perform meta-analysis to evaluate whether pelvic floor training devices are as effective as traditional supervised pelvic floor physical therapy.; Conclusion: Commercially available home pelvic floor training devices are effective in increasing strength of pelvic floor muscles and in the treatment of pelvic floor disorders.; Competing Interests: Financial Disclosure Jon F. Pennycuff reports funding from Renovia Inc., maker of the Leva device, for investigator-initiated research. Money was paid to his institution from the American Cancer Society (Institutional Research Grant). Ali Borazjani reports receiving payment from COSM Medical Corp. for stock options and consulting. Cheryl Iglesia reports the following: Editorial Board: OBGManagement; FPRMS journal SoMe editor Exec Board: Society Gyn Surgeons NICHD PFDN Advisory Board Advisory Board: Patty Brisben Foundation, Healthy Women, Research support payable to MedStar health Research Institute: FFHA Foundation for female health awareness, Renovia, National vulvodynia Association. Haijun Wang did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Penson Richard, T., et al. (2023). "Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer." The Oncologist 28(3): 252-257.
	Background: Iniparib (BSI-201), a novel anticancer agent thought to have poly(ADP-ribose) polymerase (PARP) inhibitory activity and synergy with both gemcitabine and carboplatin (GC) was evaluated in 2 cohorts with GC.; Methods: Parallel multicenter, single-arm, phase II studies using a Simon two-stage design. Eligible patients had a histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma and demonstration of platinum-sensitive (≥6 months [mo]) or -resistant disease (relapse 2-6 mo post-platinum). Carboplatin (AUC 4 IV day 1), gemcitabine (1000 mg/m2 IV days 1 and 8), and iniparib (5.6 mg/kg IV days 1, 4, 8, and 11) were given on a 21-day cycle.; Results: The overall response rate (ORR RECIST 1.0) in platinum sensitive disease was 66% (95% CI, 49-80) with a higher response rate in the 15 pts with germline BRCA mutations (gBRCAmut) (73%). Median PFS was 9.9 (95% CI, 8.2-11.3) months. In the platinum resistant population the ORR was 26% (95% CI, 14-42), however in the 11 pts for whom BRCA mutation was present, the best overall response was PR in 5 (46%). Median PFS was 6.8 months (range, 5.7-7.7 months). Notably, among the 17 CA-125-response-evaluable patients who did not achieve tumor response, 7 (41.2%) patients had a CA125 response, and 93% has clinical benefit (CR + PR + SD). The GCI combination was generally well tolerated despite a high incidence of thrombocytopenia and neutropenia, with no new toxicities.; Conclusions: Given the subsequent lack of efficacy demonstrated for iniparib in breast cancer, these are studies of GC and demonstrate a higher than traditionally appreciated activity in patients with platinum-sensitive and -resistant recurrent ovarian cancer, especially in patients that harbor a BRCA mutation, resetting the benchmark for efficacy in phase II trials. (ClinicalTrials.gov Identifiers: NCT01033292 & NCT01033123). (© The Author(s) 2023. Published by Oxford University Press.)

Pentland, V., et al. (2022). "Does Walking Reduce Postpartum Depressive Symptoms? A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Journal of women's health (2002) 31(4): 555-563.
	Background: Rising demands for traditional postpartum depression (PPD) treatment options ( e.g. , psychiatry), especially in the context of the COVID-19 pandemic, are increasingly difficult to meet. More accessible treatment options ( e.g. , walking) are needed. Our objective is to determine the impact of walking on PPD severity. Methods: A structured search of seven electronic databases for randomized controlled trials published between 2000 and July 29, 2021 was completed. Studies were included if walking was the sole or primary aerobic exercise modality. A random-effects meta-analysis was conducted for studies reporting PPD symptoms measured using a clinically validated tool. A simple count of positive/null effect studies was undertaken as part of a narrative summary. Results: Five studies involving 242 participants were included (mean age = ∼28.9 years; 100% with mild-to-moderate depression). Interventions were 12 ( n = 4) and 24 ( n = 1) weeks long. Each assessed PPD severity using the Edinburgh Postnatal Depression Scale (EPDS), and was included in the meta-analysis. The pooled effect estimate suggests that relative to controls walking yielded clinically significant decreases in mean EPDS scores from baseline to intervention end (pooled mean difference = -4.01; 95% CI: -7.18 to -0.84, I 2 = 86%). The narrative summary provides preliminary evidence that walking-only, supervised, and group-based interventions, including 90-120+ minutes per week of moderate-intensity walking, may produce greater EPDS reductions. Conclusions: While limited by a relatively small number of included studies, pooled effect estimates suggest that walking may help mothers manage PPD. This is the first-time walking as treatment for PPD, an exercise modality that uniquely addresses many barriers faced by mothers, has been summarized in a systematic way. Trial registration: PROSPERO (CRD42020197521) on August 16th, 2020.

Pepin, K., et al. (2020). "Safety of Minimally Invasive Tissue Extraction in Fibroid Management, A Systematic Review." Journal of Minimally Invasive Gynecology 28(3): 619-643.
	OBJECTIVE: This review seeks to establish the incidence of adverse outcomes associated with minimally invasive tissue extraction at the time of surgical procedures for fibroids. DATA SOURCES: Articles published in the following databases without date restrictions: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and Trials. Search conducted on March 25, 2020. METHODS OF STUDY SELECTION: Included studies evaluated minimally invasive surgical procedures for uterine fibroids involving morcellation. This review did not consider studies of non-uterine tissue morcellation, studies involving uterine procedures other than hysterectomy or myomectomy, studies involving morcellation of known malignancies, nor studies concerning hysteroscopic myomectomy. A total of 695 studies were reviewed, with 185 studies included for analysis. TABULATION, INTEGRATION, AND RESULTS: The following variables were extracted: patient demographics, study type, morcellation technique and adverse outcome category. Adverse outcomes included: prolonged operative time, morcellation time, blood loss, direct injury from a morcellator, dissemination of tissue (benign or malignant) and disruption of the pathologic specimen. CONCLUSION: Complications related to morcellation are rare, however there is a great need for higher-quality studies to evaluate associated adverse outcomes.

Pepin, K., et al. (2021). "Safety of Minimally Invasive Tissue Extraction in Myoma Management: A Systematic Review." Journal of Minimally Invasive Gynecology 28(3): 619-643.
	Objective: This review seeks to establish the incidence of adverse outcomes associated with minimally invasive tissue extraction at the time of surgical procedures for myomas.; Data Sources: Articles published in the following databases without date restrictions: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and Trials. Search was conducted on March 25, 2020.; Methods of Study Selection: Included studies evaluated minimally invasive surgical procedures for uterine myomas involving morcellation. This review did not consider studies of nonuterine tissue morcellation, studies involving uterine procedures other than hysterectomy or myomectomy, studies involving morcellation of known malignancies, nor studies concerning hysteroscopic myomectomy. A total of 695 studies were reviewed, with 185 studies included for analysis.; Tabulation, Integration, and Results: The following variables were extracted: patient demographics, study type, morcellation technique, and adverse outcome category. Adverse outcomes included prolonged operative time, morcellation time, blood loss, direct injury from a morcellator, dissemination of tissue (benign or malignant), and disruption of the pathologic specimen.; Conclusion: Complications related to morcellation are rare; however, there is a great need for higher quality studies to evaluate associated adverse outcomes. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Pereira, G. M. V., et al. (2021). "Effect of radiofrequency and pelvic floor muscle training in the treatment of women with vaginal laxity: A study protocol." PloS One 16(11): e0259650.
	BACKGROUND: Vaginal laxity is an underreported condition that negatively affects women's sexual function and their relationships. Evidence-based studies are needed to better understand this complaint and to discuss its treatment options. Thus, we present a study protocol to compare the effect of radiofrequency and pelvic floor muscle training in the treatment of women with complaints of vaginal laxity. METHODS/DESIGN: This is a prospective, parallel-group, two-arm, randomized clinical trial (Registry: RBR-2zdvfp-REBEC). Participants will be randomly assigned to one of the two groups of intervention (Radiofrequency or Pelvic Floor Muscle Training). The study will be performed in the Urogynecology outpatient clinic and in the physiotherapy outpatient clinic at the State University of Campinas-UNICAMP and will include women aged ≥ 18 years and with self-reported complaints of vaginal laxity. Participants will be assessed at baseline (pre-intervention period) and will be followed up in two periods: first follow-up (30 days after intervention) and second follow-up (six months after intervention). EXPECTED RESULTS: The results of this randomized clinical trial will have a positive impact on the participants' quality of life, as well as add value to the development of treatment options for women with complaints of vaginal laxity. TRIAL REGISTRATION: Registry: RBR-2zdvfp-Registro Brasileiro de Ensaios Clínicos-REBEC (19/02/2020).

Pereira, J. V. B. and T. Lim (2021). "Hyperthyroidism in gestational trophoblastic disease - a literature review." Thyroid Research 14(1): 1.
	Objective: Gestational trophoblastic disease (GTD) is a group of pregnancy-related disorders that arise from abnormal proliferation of placental trophoblast. Some patients with GTD develop hyperthyroidism, a rare but potentially life-threatening complication requiring early detection and management. Existing literature on hyperthyroidism in GTD is scant. This review aims to analyse the epidemiology, pathophysiology and management of this phenomenon. Method(s): A comprehensive search of MEDLINE, EMBASE and Cochrane Library was performed to obtain articles that explored hyperthyroidism in GTD. A total of 405 articles were screened and 228 articles were considered for full-text review. We selected articles that explored epidemiology, pathophysiology and outcomes/management of hyperthyroidism in GTD. Result(s): The pathophysiology of hyperthyroidism in GTD is well-investigated. Placental trophoblastic tissue secretes excessive hCG, which is structurally similar to thyroid stimulating hormone and also has enhanced thyrotropic activity compared to normal hCG. The incidence and prevalence of hyperthyroidism in GTD varies worldwide, with lower rates associated with high uptake of early antenatal screening and early GTD detection. No clear risk factors for hyperthyroidism in GTD were identified. While hyperthyroidism can be definitively managed with surgical evacuation of the uterus, severe complications associated with hyperthyroidism in GTD have been reported, including thyroid storm-induced multi-organ failure, ARDS, and pulmonary hypertension. Conclusion(s): Early detection of GTD is critical to prevent development of hyperthyroidism and its associated complications. Hyperthyroidism should be recognised as an important perioperative consideration for women undergoing surgery for GTD, and requires appropriate management. Future studies should explore risk factors for hyperthyroidism in GTD, which may facilitate earlier identification of high-risk women.Copyright © 2021, The Author(s).

Pereira, R., et al. (2021). "Effects of recreational team handball on bone health, postural balance and body composition in inactive postmenopausal women - A randomised controlled trial." Bone 145: 115847.
	This study reports the effects of a recreational team handball exercise programme (randomised controlled trial, RCT) on bone health, postural balance and body composition in inactive postmenopausal women without previous experience of the sport. Sixty‐seven postmenopausal women (68.3 ± 6.2 years, stature 156.9 ± 5.8 cm, body mass 65.6 ± 9.6 kg, body fat 40.9 ± 5.9%, VO2peak 25.2 ± 3.6 mL·min−1·kg−1) were randomised into team handball (THG, n = 41) and control (CG, n = 26) groups. During the 16‐week intervention period, THG performed two to three 60‐min training sessions per week, while CG continued with their habitual physical activity. Bone mineral density (BMD) and content (BMC), biochemical bone formation (osteocalcin (OC), procollagen type‐1 amino‐terminal propeptide (P1NP)) and resorption (carboxy‐terminal type‐1 collagen crosslinks (CTX)) markers, postural balance, body fat and lean mass were evaluated at baseline and post intervention. A time x group interaction (p ≤ 0.02) was shown for lumbar spine BMD (+1.5%) and BMC (+2.3%), P1NP (+37.6 ± 42.4%), OC (+41.9 ± 27.0%) and postural balance (−7 ± 37% falls), in favour of THG with no changes in CG. This RCT showed that short‐term recreational team handball practice had an impact on bone turnover and was effective for improving bone health and postural balance in postmenopausal women without previous experience of the sport, hence potentially helping to reduce the risk of falls and fractures.

Pérez, F., et al. (2021). "Effects of the intake of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids in a sample of postmenopausal women with metabolic syndrome: a randomized, triple-blind, placebo-controlled clinical trial." Nutricion hospitalaria 38(5): 983‐992.
	Introduction: metabolic syndrome in postmenopausal women can improve with a healthy diet. Objectives: to evaluate whether a dietary intervention with dairy products naturally enriched with selenium and omega‐3 polyunsaturated fatty acids increases selenium plasma levels and improves cardiovascular risk factors in postmenopausal women with metabolic syndrome. Material and methods: a randomized, triple‐blind, controlled clinical trial carried out in GP surgeries. Recruitment: April 2018, 46 postmenopausal women with metabolic syndrome who were frequent dairy consumers. Randomization: 23 in control group and 23 in experimental group. Intervention: consumption of dairy products naturally enriched with selenium and omega‐3 polyunsaturated fatty acids (milk, yogurt, fresh cheese) for three months. Controls took conventional dairy. Primary endpoint: plasma selenium levels; secondary endpoints: metabolic syndrome criteria. Registration number 2018/256, Galicia Ethics Committee. Results: in all, 23 women in the control group and 21 in the intervention group completed the trial. Selenium increased in the intervention group (7.2 µg/L, 95 % CI, 3.7/10.8) compared to the control group (‐4.5 µg/L, 95 % CI, ‐8/‐1) (p < 0.001) and very low‐density lipoprotein cholesterol decreased (‐2.3 mg/dL, 95 % CI, ‐5.6/1) compared to the control group (1.9 mg/dL, 95 % CI, ‐0.7/4.5) (p = 0.043). Waist circumference (p = 0.010), body mass index (p = 0.047) and high‐density lipoprotein cholesterol (p < 0.001) in the experimental group improved in comparison to baseline measurements. Conclusions: an intervention with dairy products naturally enriched with selenium and omega‐3 in a sample of postmenopausal women with metabolic syndrome can improve plasma selenium levels and very low‐density lipoprotein cholesterol.

Pérez-Castrillón, J. L., et al. (2021). "Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial." Journal of bone and mineral research 36(10): 1967‐1978.
	Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1‐year, phase III‐IV, double‐blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D‐deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25‐hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention‐to‐treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment‐related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Pérez-Castrillón José, L., et al. (2023). "Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial." Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38(4): 471-479.
	Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). (© 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Perez-Fidalgo, J. A., et al. (2021). "Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study)." ESMO Open 6(4): 100212.
	BACKGROUND: There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. PATIENTS AND METHODS: Patients with high-grade serous or endometrioid ovarian carcinoma and one previous PROC recurrence were enrolled regardless of BRCA status. Patients with ≤4 previous lines (up to 5 in BRCA-mut) with at least one previous platinum-sensitive relapse were included; primary PROC was allowed only in case of BRCA-mut. Patients initially received six cycles of olaparib 300 mg b.i.d. (biduum) + intravenous pegylated liposomal doxorubicin (PLD) 40 mg/m2 (PLD40) every 28 days, followed by maintenance with olaparib 300 mg b.i.d. until progression or toxicity. The PLD dose was reduced to 30 mg/m2 (PLD30) due to toxicity. The primary endpoint was progression-free survival (PFS) at 6 months (6m-PFS) by RECIST version 1.1. A proportion of 40% 6m-PFS or more was considered of clinical interest. RESULTS: From 2017 to 2020, 31 PROC patients were included. BRCA mutations were present in 16%. The median of previous lines was 2 (range 1-5). The overall disease control rate was 77% (partial response rate of 29% and stable disease rate of 48%). After a median follow-up of 10 months, the 6m-PFS and median PFS were 47% and 5.8 months, respectively. Grade ≥3 treatment-related adverse events occurred in 74% of patients, with neutropenia/anemia being the most frequent. With PLD30 serious AEs were less frequent than with PLD40 (21% versus 47%, respectively); moreover, PLD30 was associated with less PLD delays (32% versus 38%) and reductions (16% versus 22%). CONCLUSIONS: The PLD-olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m2 is better tolerated in the combination.

Perez-Fidalgo, J. A., et al. (2022). "Cost-effectiveness of Olaparib plus Bevacizumab versus Bevacizumab in the maintenance of patients with HRD+ advanced ovarian cancer after response to firstline platinum-based chemotherapy in Spain." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), monotherapy as first-line maintenance treatment has shown to be cost-effective in ovarian cancer (OC) patients with BRCA mutations in Spain. Regardless of BRCA status, patients with homologous recombination deficiency positive (HRD+) also benefit from PARPi following first-line platinum-based therapy. PAOLA-1 trial confirmed that adding Olaparib to bevacizumab (BEV) significantly increased progression-free survival (PFS) in OC patients. The aim of this study was to assess the cost-effectiveness of Olaparib plus BEV versus BEV monotherapy for the maintenance treatment of HRD+ advanced OC patients after response to first-line platinum-based therapy plus BEV from Spanish National Health System perspective. Method(s): A lifetime partitioned survival model with monthly cycles and four health states (PFS, first progression, second progression, and death) was developed. Long-term survival defined as 60 months was included in the mixed survival model as a landmark to extrapolate PFS from the PAOLA-1 trial. Weibull distribution was selected as the most accurate survival model for PFS extrapolation. Time to second progression, and overall survival (OS) were extrapolated using parametric survival models. Mortality was obtained from the OS and adjusted by Spanish mortality rates. Health state utilities and adverse event (AE) frequencies were obtained from PAOLA-1. An expert panel validated data and assumptions. Direct costs including drug acquisition and administration, follow-up, subsequent therapies, AE, and end-of-life were obtained from local sources. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as cost per quality- adjusted life-years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model. Result(s): Base-case analysis of Olaparib plus BEV compared with BEV showed an ICER of e24,371 per QALY gained. Discount rates applied to outcomes and the cost of Olaparib generated the most significant changes in the ICER. PSA demonstrated that Olaparib plus BEV had a 49.5% and 90.3% probability of being cost-effective versus BEV at a willingness- to-pay of e25,000 and e60,000 per QALY gained, respectively. Conclusion(s): Olaparib plus BEV is a cost-effective maintenance therapy compared with BEV for patients with HRD+ advanced OC in Spain.

Perez-Fidalgo José, A., et al. (2023). "Clinical and molecular signature of survival and resistance to olaparib plus pegylated liposomal doxorubicin in platinum-resistant ovarian cancer: a stratified analysis from the phase II clinical trial ROLANDO, GEICO-1601." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(6): 929-936.
	Objective: To determine the potential prognostic value of clinical and molecular biomarkers in the survival of patients with platinum-resistant ovarian cancer treated with olaparib and pegylated liposomal doxorubicin.; Methods: ROLANDO was a single-arm phase II trial that included patients with high-grade serous or endometrioid tumors and at least one previous platinum-resistant recurrence regardless of BRCA status. Patients received 6 cycles of pegylated liposomal doxorubicin every 28 days plus olaparib 300 mg twice daily. followed by olaparib 300 mg twice daily; monotherapy until progression or unacceptable toxicity. Prognostic factors including previous lines (and platinum-containing ones), BRCA mutation status, previous bevacizumab, CA-125 levels, and the neutrophil/lymphocyte ratio, lymphocyte/monocyte ratio, and platelet/lymphocyte ratio calculated at inclusion were analyzed through a multivariate logistic regression and factor analysis of mixed data.; Results: Thirty-one patients were included. Median age was 57 years (range 43-75), Eastern Cooperative Oncolgy Group performance status 0/1: 32.3%/67.7% and BRCA mutated: 16.1%. Prior treatment lines were >2 lines: 14 (45.2%) patients, ≥2 platinum lines: 21 patients (67.7%) and previous bevacizumab 19 (61.3%) patients. CA-125 was >2 upper limit normal in 24 (77.4%) patients. A high neutrophil/lymphocyte ratio was associated with worse overall survival by univariate/multivariate regression model (HR=11.18; 95% CI 1.1 to 114.5; p=0.042). No other factors were associated with overall survival in the multivariate model. A multifactorial signature based on clinical and molecular baseline characteristics was capable of defining six patient clusters. Three of these clusters had significantly better prognosis, with a median overall survival of 21.3 months (95% CI 12.2 to not reached).; Conclusions: High neutrophil/lymphocyte ratio at platinum-resistant relapse indicated poor prognosis in patients treated with olaparib plus pegylated liposomal doxorubicin. A multifactorial clinical signature was more precise than single variables for implying the prognosis and may help in therapeutic assignment after further validation in large prospective cohorts.; Competing Interests: Competing interests: MJR has served on advisory boards for MSD, AstraZeneca, Roche, GSK, Clovis, PharmaMar, and received support for travel or accommodation from Roche, AstraZeneca, MSD and PharmaMar. YGG declares participating in advisory boards from GSK, AstraZeneca, and Pharmamar, and declares fees from travel grants and speaker’s bureau from Roche, AstraZeneca, Pharmamar, MSD, GSK. ASB declares participating in advisory boards for MSD, AstraZeneca, GSK, Clovis, PharmaMar, and declares receiving support for travel from MSD and GSK, and speaker's bureau from MSD, AstraZeneca, GSK, Clovis. PE-G has served on advisory boards for MSD, AstraZeneca, GSK, Clovis, PharmaMar, and received support for travel or accommodation from GSK, AstraZeneca, MSD, and PharmaMar. All the other authors declare no conflicts of interest. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Pérez-López, A., et al. (2022). "Circulating myokines IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity." European Journal of Sport Science 22(9): 1426-1435.
	To examine the effects of a time-matched endurance vs. concurrent training on circulating IL-6, IL-13, IL-15, IL-15Ra, FGF21 levels in postmenopausal women with obesity, and to determine these myokines response to endurance training pre- and postmenopause. Thirty-five sedentary postmenopausal women with obesity were randomly divided into endurance training (EN1, N = 10), concurrent training (CON, N = 13) or no training group (CT, N = 12). Additionally, twelve sedentary premenopausal women with obesity were added to an endurance training group (EN2, N = 12). Participants took part in a 12-week supervised intervention, performing 3 sessions/week of 60 min/session. Before and after the interventions, body composition and fitness were assessed, and blood samples obtained to measure serum myokines levels. Total fat mass decreased in all exercised groups (CON,-5.2%; EN1,-5.3%; EN2,-5.6%). In postmenopausal women, serum IL-6, IL-15 and IL-15Ra decreased after training ( P <0.01), finding a pronounced reduction in IL-6 (-42% vs. -16%) and IL-15 (-50% vs. -31%) when comparing EN1 to CON ( P <0.05). Serum FGF21 was only reduced in the EN1 (-27%; P =0.012). While EN1 and EN2 comparison, reported differences for IL-15Rα concentration (-28% vs. -40%; P =0.023). Finally, in EN2, the delta change of fat mass and IL-6, IL-15 and IL-15Rα were associated ( r = 0.605; r = 0.546; r = 0.515; P <0.05). IL-13 showed undetected concentrations. Circulating IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity. Endurance training promotes a higher reduction of these myokines, potentially activating their intricate immune and fat mass regulation roles in postmenopausal women with obesity.

Pérez-Medina-Carballo, R., et al. (2023). "The circadian variation of sleep and alertness of postmenopausal women." Sleep 46(2).
	Study Objectives: Several factors may contribute to the high prevalence of sleep disturbances occurring in postmenopausal women. However, the contribution of the circadian timing system to their sleep disturbances remains unclear. In the present study, we aim to understand the impact of circadian factors on changes of sleep and alertness occurring after menopause.; Methods: Eight healthy postmenopausal women and 12 healthy young women in their mid-follicular phase participated in an ultradian sleep-wake cycle procedure (USW). This protocol consisted of alternating 60-min wake periods and nap opportunities for ≥ 48 h in controlled laboratory conditions. Core body temperature (CBT), salivary melatonin, self-reported alertness, and polysomnographically recorded sleep were measured across this procedure.; Results: In both groups, all measures displayed a circadian variation throughout the USW procedure. Compared to young women, postmenopausal women presented lower CBT values, more stage N1 and N2 sleep, and number of arousals. They also showed a reduced amplitude of the circadian variation of melatonin, total sleep time (TST), sleep onset latency (SOL), stage N3 sleep, and alertness levels. Postmenopausal women fell asleep faster and slept more during the biological day and presented higher alertness levels during the biological night than young women.; Conclusion: These results support the hypothesis of a weakened circadian signal promoting sleep and wakefulness in older women. Aging processes including hormonal changes may be main contributors to the increased sleep-wake disturbances after menopause. (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Perfors, I. A. A., et al. (2022). "Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial." BMC primary care 23(1): 145.
	BACKGROUND: The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis. METHOD(S): We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a "Time Out consultation" (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression. RESULT(S): We included 154 patients (control n =77, intervention n=77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD+/-11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (-14.2 (95%CI -27.0;-1.3)), availability (-15,9 (-29.1;-2.6)) and information provision (-15.2 (-29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively). CONCLUSION(S): In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention. TRIAL REGISTRATION: GRIP is retrospectively (21/06/2016) registered in the 'Netherlands Trial Register' (NTR5909).Copyright © 2022. The Author(s).

Pergialiotis, V., et al. (2019). "Survival outcomes of ovarian cancer patients treated with secondary cytoreductive surgery for isolated lymph node recurrence: A systematic review of the literature." International journal of surgery (London, England) 69: 61-66.
	Background: Isolated lymph node recurrence (ILNR) is present in 12-37% of recurrences in ovarian cancer patients. Although several studies have investigated the impact of secondary cytoreduction in these cases, consensus still lacks concerning their optimal management. The purpose of the present review is to investigate whether secondary cytoreduction benefits patients with ILNR in terms of overall survival (OS) and post-relapse survival (PRS).; Method: The present systematic review was designed using the PRISMA and AMSTAR guidelines and has been registered with PROSPERO (CRD42019122854). We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until February 2019.; Results: Overall, eight studies where included that recruited a total number of 479 women. Current evidence suggests that ILNR in EOC patients should be clearly distinguished from recurrences in other sites (including peritoneal and parenchymal) as their course seems to be less aggressive. Furthermore, the implementation of secondary cytoreduction as an adjunct to standard chemotherapy should be taken into consideration in this specific group of patients as the PRS may easily reach and even extend beyond 5 years. Prolonged survival (>110 months) may be seen as a realistic target for a significant number of these patients when systematic lymphadenectomy is performed.; Conclusion: The findings of our review suggest that patients with ILNR should be treated with a combined surgical and chemotherapeutic approach to optimize survival outcomes. However, further studies are needed to reach firm conclusions as current evidence is based in low quality studies. (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Pergialiotis, V., et al. (2022). "The impact of adjuvant hysterectomy on survival outcomes of patients with locally advanced cervical cancer: A network meta-analysis." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 48(1): 261-267.
	Background and Objectives: Various articles have addressed the impact of hysterectomy on survival outcomes of patients with locally advanced cervical cancer (LACC). This study was designed to evaluate whether treatment modalities that include hysterectomy as an option for the treatment of LACC patients are superior to standard chemo-radiotherapy.; Methods: Literature search was performed using the Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Clinicaltrials.gov databases. Observational (prospective and retrospective) and randomized trials that included adjuvant hysterectomy in at least one treatment group. A network meta-analysis was carried out in R 3.4.3 using the pcnetmeta package, which uses a Bayesian hierarchical model. The credibility of evidence was appraised with the Confidence In Network Meta-Analysis (CINeMA) tool.; Results: Overall, 14 studies were included in the present systematic review that involved 2302 patients with LACC. Every potential combination of external beam radiotherapy, intracavitary brachytherapy, chemotherapy and surgery was considered to be eligible for inclusion. The results of the network meta-analysis suggested that the various treatment alternatives did not differ in terms of survival outcomes. Furthermore, the qualitative analysis revealed that hysterectomy was accompanied by considerable perioperative morbidity; therefore, rendering its addition to the treatment scheme of LACC patients inappropriate.; Conclusions: Patients with LACC do not seem to benefit substantially by the addition of hysterectomy to standard chemo-radiotherapy. Moreover, the operation is accompanied by substantial perioperative morbidity, thus, its implementation in clinical practice should be avoided.; Competing Interests: Declaration of competing interest The authors report no conflict of interest. (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Pergialiotis, V., et al. (2022). "Is There a Survival Benefit of Adjuvant Chemotherapy in Stage IC1 Epithelial Ovarian Cancer Patients? A Meta-Analysis." Current oncology (Toronto, Ont.) 29(8): 5763-5773.
	The purpose of the present systematic review is to clarify whether adjuvant chemotherapy improves survival rates in women with stage IC1 ovarian cancer. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We considered comparative observational studies and randomized trials that investigated survival outcomes (progression-free (PFS) and overall survival (OS)) among women with intraoperative rupture of early-stage epithelial ovarian cancer who received adjuvant chemotherapy and those that did not. Eleven studies, which recruited 7556 patients, were included. The risk of bias was defined as moderate after assessment with the Risk of Bias in non-Randomized Trials tool. Meta-analysis was performed with RStudio. Seven studies investigated the impact of adjuvant chemotherapy on recurrence-free survival of patients experiencing intraoperative cyst rupture for otherwise stage I ovarian cancer. The outcome was not affected by the use of adjuvant chemotherapy as the effect estimate was not significant (HR 1.24, 95% CI 0.74, 2.04). The analysis of data from 5 studies similarly revealed that overall survival rates were comparable among the two groups (HR 0.75, 95% CI 0.54, 1.05). This meta-analysis did not detect any benefit from adjuvant chemotherapy for stage IC ovarian cancer patients with cyst rupture. However, conclusions from this investigation are limited by a study population which included multiple histologic subtypes, high and low grade tumors and incompletely staged patients.

Pergialiotis, V., et al. (2022). "Quality of life of ovarian cancer patients treated with combined platinum taxane chemotherapy: a systematic review of the literature." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30(9): 7147-7157.
	Purpose: Chemotherapy is the cornerstone of adjuvant therapy in ovarian cancer. Its impact on the quality of life (QoL) has been addressed in several studies; however, several misperceptions concerning this affect patient counseling and physicians' ability to overcome patient fears. In the present systematic review, we sought to accumulate current evidence in the field in order to help establish robust information that will help physicians answer patients' questions.; Methods: The present systematic review is based on the PRISMA guidelines. Studies that evaluated patient QoL pre-, during, and post-chemotherapy with the use of the QLQC-30 were selected for inclusion. Their methodological quality was assessed with the before-after studies tool that is proposed by the National Institute of Health (NIH).; Results: Ten studies that involved 5181 patients were included in the present systematic review. The risk of bias and methodological quality of included studies was of good and fair overall quality. Retrieved data suggest there is substantial evidence that points toward improved global QoL among ovarian cancer patients treated with taxanes-platinum combination therapy. Individual outcomes evaluated with the QLQ-C30 also provide positive results, although underreporting was noted.; Conclusion: Despite the significant heterogeneity in outcome reporting, the findings of this study reveal the significant benefit of combined platinum taxane chemotherapy on the QoL of ovarian cancer patients and can be used for patients counseling in order to reduce refusals that arise from fear of adverse effects that may negatively affect QoL. Graphical abstract. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pergialiotis, V., et al. (2020). "Perioperative blood transfusion and ovarian cancer survival rates: A meta-analysis based on univariate, multivariate and propensity score matched data." European Journal of Obstetrics, Gynecology, and Reproductive Biology 252: 137-143.
	The negative impact of perioperative blood transfusion on survival outcomes has been reported in several cancer types. The purpose of the present study is to summarize existing evidence in ovarian cancer patients. We searched the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases for observational and randomized trials that assessed the impact of perioperative blood transfusion on the disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients that undergone debulking surgery were selected for inclusion. The methodological quality of the included studies was assessed by using the Newcastle-Ottawa Scale. Statistical meta-analysis was performed with the RevMan 5.3 software using the Der-Simonian Laird random effects model. Seven studies were identified which included 2341 ovarian cancer patients. Meta-analyses that were based on univariate and multivariate reporting revealed that perioperative blood transfusion had a significant negative impact on the patient`s OS rates (OR 1.78, 95 %CI 1.16, 2.74 and OR 1.31, 95 %CI 1.00, 1.71 respectively). Disease free survival rates were also influenced according to the results of the univariate analysis (OR 1.58, 95 %CI 1.14, 2.19), however, the effect was not significant in the multivariate analysis. The analysis that was based on propensity score matched populations did not reveal differences among transfused and non-transfused. Concluding, the findings of our meta-analysis suggest that transfusion of blood products during the perioperative period is not an independent factor that may affect survival outcomes of ovarian cancer patients. Nevertheless, it should be noted that patients that receive transfusion have several potential confounders that may affect their survival outcomes.; Competing Interests: Declaration of Competing Interest The authors report that they have no conflicts of interest to disclose. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pergialiotis, V., et al. (2023). "Tumor free distance from serosa and survival rates of endometrial cancer patients: A meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 286: 16-22.
	Myometrial invasion and its extent have been directly associated with the risk of relapse as well as the overall survival of endometrial cancer patients. Tumor free distance from the serosal surface of the uterine wall has been investigated the last years by several studies, however, to date, its importance remains unknown. The present meta-analysis is based on a systematic search of the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases and has been designed according to the PRISMA guidelines. Nine studies were included in the present systematic review that recruited pathology slides from 1,598 endometrial cancer patients and their meta-analysis indicated that TFD was significantly associated with the progression free survival of patients with endometrial cancer (OR 0.36, 95% CI 0.20, 0.65). The disease specific survival was not affected by the TFD (OR 0.30, 95% CI 0.09, 1.01). Sensitivity analyses revealed, however, that both the progression free and overall survival rates were associated with TFD. Significant discrepancies were observed in terms of histological subtypes and stage of the disease among included patients, hence, the actual importance of TFD in specific subgroups remains unknown. Future studies must evaluate the importance of this pathology marker particularly in patients with endometrioid subtypes and early-stage disease, as it is believed that in this group its importance will be more predictive as it will not be skewed by the presence of more important factors such as more aggressive histology and advanced stage disease.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Perihan, C., et al. (2021). "The Effect of Acceptance and Commitment Therapy on Infertility Related Psychological Problems : A Systematic Review."
	
Permanente, K., et al. (2021). Accelerating Implementation of Mindful Mood Balance for Moms.
	No Results Available Behavioral: MMBFM program with clinician coach support|Behavioral: MMBFM program with peer coach support|Behavioral: Patient facing strategy intervention arm|Behavioral: Patient facing plus clinic facing strategy intervention arm Change in Patient Health Questionnaire 9-item (PHQ-9) scores from baseline through 3 months postpartum|Reach|Change in Generalized Anxiety Disorder 7-item (GAD-7) questionnaire scores from baseline through 3 months postpartum|Change in Perceived Stress Scale scores from baseline through 3 months postpartum|Change in Attitudes Toward Motherhood (AToM) Scale scores from baseline through 3 months postpartum|Change in Short Form 12 (SF-12) scores from baseline through 3 months postpartum|The TWente Engagement with Ehealth Technologies Scale (TWEETS)|Client Satisfaction Questionnaire (CSQ) Female Not Applicable 423 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Health Services Research U19MH121738|5U19MH121738-02 August 30, 2023

Perrone Anna, M., et al. (2023). "Post-operative residual disease and number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(8): 1270-1278.
	Background: The optimal number of neoadjuvant chemotherapy cycles in patients with advanced ovarian cancer is still disputed.; Objective: To evaluate the impact of the number of neoadjuvant chemotherapy cycles and role of optimal cytoreduction on the prognosis of patients with advanced ovarian cancer.; Methods: Clinical and pathological details were examined. Patients were evaluated combining the number of cycles of neoadjuvant chemotherapy-namely, 'interval debulking surgery' after up to four neoadjuvant chemotherapy cycles, and 'delayed debulking surgery' after more than four cycles of therapy.; Results: A total of 286 patients were included in the study. Complete cytoreduction with no residual peritoneal disease (CC0) was achieved in 74 (74%) patients with interval debulking surgery and 124 (66.7%) patients with delayed interval debulking. Of those with residual disease, there were 26/88 (29.5%) patients in the interval debulking surgery group and 62/88 (70.5%) patients in the delayed debulking surgery group. Comparison of patients with delayed debulking-CC0 and interval debulking-CC0 showed no difference in progression-free survival (p=0.3) or overall survival (p=0.4), while significantly worse outcomes were observed in patients with interval debulking-CC1 (p=0.02 and p=0.04, respectively). Specifically, patients with interval debulking-CC1 had an approximately 67% increased risk of disease progression (p=0.04; HR=2.01 (95% CI 1.04 to 4.18)) and a 69% higher risk of death than patients with delayed debulking-CC0 (p=0.03; HR=2.34 (95% CI 1.11 to 4.67)).; Conclusion: Increasing the number of neoadjuvant chemotherapy cycles does not worsen patient outcomes if complete resection is achieved. Nevertheless, additional prospective trials are necessary to establish the optimum number of neoadjuvant chemotherapy cycles.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Person, K., et al. (2022). "A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oteseconazole (VT-1161) Oral Capsules in the Treatment of Subjects with Recurrent Vulvovaginal Candidiasis (VIOLET)." American Journal of Obstetrics and Gynecology 226(2): 292.
	Objectives: RVVC affects nearly 138 million women globally each year. Currently there are no FDA approved treatment options. Two Phase 3 studies evaluated the efficacy and safety of Oteseconazole (VT-1161) in the treatment of women with recurrent vulvovaginal candidiasis (RVVC). Method(s): 656 patients with a history of RVVC (3 or more acute episodes within the previous 12 months) were enrolled at 181 centers in 11 countries. Patients were required to present with a vulvovaginal signs and symptoms score of >=3 and a positive KOH. Following treatment of the presenting acute infection with fluconazole, patients were randomized to 1) 150 mg VT-1161 once-daily for 7 days, then 150 mg once-weekly for 11 weeks or 2) matching placebo regimen for 12 weeks. Patients were followed for 48 weeks. Result(s): Both studies achieved the primary efficacy endpoint by demonstrating significant differences between oteseconazole and placebo for the proportion of subjects with >=1 culture-verified acute VVC episode through the 48-week Maintenance Phase in the ITT Population. Specifically, over 90% of women randomized to receive oteseconazole did not experience a recurrence during the 48-week maintenance phase compared to approximately 40% in the control group (p <0.001). Study completion was high and similar in both oteseconazole and placebo groups. Premature study discontinuations were similar between groups and there were no notable differences in demographics and baseline characteristics. Subject compliance was high with no notable differences between treatment groups. The percentage of subjects who had >=1 treatment-emergent adverse event (TEAE) was similar in the oteseconazole and placebo groups. The most frequently reported individual TEAEs were nasopharyngitis, bacterial vaginosis, urinary tract infection, upper respiratory tract infection, sinusitis, headache, cystitis, and back pain. The majority of subjects experienced either mild or moderately severe TEAEs. There were no drug-related SAEs and no evidence of adverse effects on pregnancy outcomes, liver function or QT intervals. Conclusion(s): Oteseconazole oral dosing was shown to be effective in the treatment of RVVC and prevention of recurrence of acute VVC episodes during the Maintenance Phase through Week 48. Oteseconazole was safe and well-tolerated.Copyright © 2021

Perutelli, A., et al. (2021). "Modified intestinal isolation bag as promising tool in promoting bowel resumption after ovarian cancer cytoreductive surgery: a randomized clinical trial." Archives of Gynecology and Obstetrics 304(3): 733-742.
	PURPOSE: Postoperative ileus (POI) impairs patient recovery, prolonging hospital stay after major surgery in ovarian cancer (OvCa) patients. Thus, intraoperative bowel isolation is expected to reduce manipulation-related impairment. The aim of this study was to investigate the impact of intraoperative intestinal isolation bag on POI in OvCa patients submitted to primary surgery. METHODS: A randomized trial including patients managed with or without isolation bag during OvCa primary surgery was conducted. Patients were selected by consecutive randomization. Primary endpoints were the time between surgery and resumption of bowel motility (as passage of first/continued flatus), assessing of postoperative nausea or vomiting and return to regular diet. Secondary endpoint was the impact of intestinal isolation bag on length of hospitalization in the two groups. RESULTS: Ninety-two patients respecting inclusion criteria were eligible to be enrolled in the study (48 patients as Group 1 and 44 patients as Group 2). Thirty-eight (79.2%) patients, in which intraoperative isolation bag was used, experienced first/continued flatus within 3 days from surgery and they were susceptible to be discharged within 5 days, compared, respectively, to 34.3% of Group 2 (n = 15). Advantages were more evident in patients whose surgery took over 220 min (OR 0.02, CI 95% 0.001-0.57; p < 0.001) despite the type of surgical effort made. CONCLUSION: Despite the small sample size, our study showed that the use of intestinal isolation bag can reduce incidence of POI and length of stay in OvCa patients submitted to primary cytoreductive surgery.

Peter, O. and O. Peter (2023). "Intrapartum Azithromycin is Effective in Reducing Postpartum Endometritis: A Systematic Review and Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	
Peter, T., et al. (2022). "The effect of medical management on ovarian endometriomas: A systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Peters, K., et al. (2023). "COMPARATIVE STUDY OF BLADDER-DIRECTED AND PELVIC FLOOR THERAPY IN WOMEN WITH INTERSTITIAL CYSTITIS/ BLADDER PAIN SYNDROME: PRELIMINARY RESULTS." Neurourology and Urodynamics 42: S76.
	Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms of pain, urgency and frequency appear to be bladder related. However, little solid evidence exists linking IC/BPS symptoms to dysfunctional bladder epithelium unless ulcers are present. Growing evidence suggests the bladder may be an innocent bystander in a more diffuse syndrome. The objective of this study is to compare IC/BPS symptom improvement in pelvic floor versus bladder directed therapies. Methods: Women 18 to 85 years with history of IC/ BPS symptoms for 6 months or more were included in the study. Participants were randomized to one of two treatment arms: 1. Pelvic Floor Physical Therapy (PFPT), 2. Bladder directed instillation of lidocaine, heparin sulphate, sodium bicarbonate, and Kenalog. All participants received twice weekly treatments for 8 consecutive weeks. Symptom improvement was assessed using 3‐day voiding diary, pain assessment, and validated questionnaires including global response assessment (GRA), Interstitial cystitis symptom index (ICSI) and Interstitial cystitis problem index (ICPI), at baseline, treatment midand end‐point (V8 and V17), and 6 months follow‐up (V18). Statistical analysis was performed using ANOVA followed by Dunnett's multiple comparison test if appropriate. Results: 31 women were enrolled and randomized to PFPT (n = 15) or Instillation (n = 16) arm with average age of 46.8 and 48.7 respectively. By end of treatment 67% in PFPT versus 54% in instillation group reported significant improvement of symptoms based on GRA. Average urinary frequency was significantly reduced in PFPT group at all time points (Fig. 1 A). Urinary frequency was resolved or improved in 75% of patients in PFPT compared to 33% in instillation group. Both treatments significantly improved Maximum pelvic pain, but reduction in pain was no longer significant in PFPT group by V18 (Fig. 1B). Pain Catastrophizing Scale scores followed the same trend. Urgency symptoms did not improve with either treatment. ICSI and ICPI scores were significantly reduced by V8 and remained constant up to V18. No severe adverse events were reported. Four patients developed urinary tract infections during treatment, 1 in PFPT and 3 in instillation group. Conclusions: Both treatments significantly improved IC/BPS symptoms, with patients in PFPT reporting higher GRA scores and frequency improvement. In contrast, instillation appeared superior in reducing maximum pelvic pain long‐term..

Petitt Matthew, S., et al. (2020). "Anesthetic and analgesic methods for gynecologic brachytherapy: A meta-analysis and systematic review." Brachytherapy 19(3): 328-336.
	Gynecologic brachytherapy procedures require targeted procedural and anesthetic needs including optimization of intra- and post-procedure analgesia, low rate of complications, and appropriate and timely transitions of care. It is uncertain whether neuraxial or general anesthesia is superior for these and other anesthetic outcomes. After a targeted search of the recent literature for anesthesia and analgesia studies for gynecologic brachytherapy, twenty studies were identified and appraised for potential review. Meta-analysis showed a decreased frequency in rescue analgesic administration in patients who underwent neuraxial anesthesia compared with general anesthesia for the procedure and literature review showed a comparable rate of anesthesia-related complications. Neuraxial anesthesia may be considered for gynecologic brachytherapy because of improved pain control, decreased opioid consumption, and similar rate of anesthesia complications. (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Pettman, D., et al. (2023). "Effectiveness of cognitive behavioural therapy-based interventions for maternal perinatal depression: a systematic review and meta-analysis." BMC Psychiatry 23(1): 208.
	Background: Depression during the perinatal period (during pregnancy and the year after childbirth) is common and associated with a range of negative effects for mothers, infants, family members, and wider society. Although existing evidence suggests cognitive behavioral therapy (CBT) based interventions are effective for perinatal depression, less is known about the effect of CBT-based interventions on important secondary outcomes, and a number of potential clinical and methodological moderators have not been examined. Method(s): A systematic review and meta-analysis primarily examined the effectiveness of CBT-based interventions for perinatal depression on symptoms of depression. Secondary aims examined the effectiveness of CBT-based interventions for perinatal depression on symptoms of anxiety, stress, parenting, perceived social support, and perceived parental competence; and explored clinical and methodological moderators potentially associated with effectiveness. A systematic search of electronic databases and other sources was performed up to November 2021. We included randomized controlled trials comparing CBT-based interventions for perinatal depression with control conditions allowing for the isolation of the effects of CBT. Result(s): In total, 31 studies (5291 participants) were included in the systematic review and 26 studies (4658 participants) were included in the meta-analysis. The overall effect size was medium (hedges g = - 0.53 [95% CI - 0.65 to - 0.40]); with high heterogeneity. Significant effects were also found for anxiety, individual stress, and perceived social support, however few studies examined secondary outcomes. Subgroup analysis identified type of control, type of CBT, and type of health professional as significant moderators of the main effect (symptoms of depression). Some concerns of risk of bias were present in the majority of studies and one study had a high risk of bias. Conclusion(s): CBT-based interventions for depression during the perinatal period appear effective, however results should be interpreted with caution given high levels of heterogeneity and low quality of included studies. There is a need to further investigate possibly important clinical moderators of effect, including the type of health professional delivering interventions. Further, results indicate a need to establish a minimum core data set to improve the consistency of secondary outcome collection across trials and to design and conduct trials with longer-term follow-up periods. Trial registration: CRD42020152254.Copyright © 2023, The Author(s).

Pfizer (2021). Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing.
	No Results Available Drug: Avelumab|Drug: Lorlatanib|Drug: Talazoparib|Drug: Pemetrexed|Drug: Axitinib|Drug: CMP 001|Drug: Utomilumab|Drug: PF04518600 Number of participants with adverse events leading to permanent discontinuation of study intervention|Number serious adverse events reported for all participants All Phase 3 262 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment B9991046|2021-002457-29 May 21, 2025

Pfizer (2021). A Study of PF-07260437 in Advanced or Metastatic Solid Tumors.
	No Results Available Drug: PF-07260437|Diagnostic Test: B7-H4 IHC Number of participants with dose limiting toxicities (DLTs) in Dose escalation|Number of participants with adverse events|Number of participants with clinically significant laboratory abnormalities|Number of participants with clinical adverse events at the recommended dose for expansion|Number of participants with clinically significant laboratory abnormalities at recommended dose for expansion|Number of participants with immune related adverse events|Single dose: Maximal concentration (Cmax)|Time to maximal plasma concentration (Tmax)|Single dose: Area Under the Curve (AUClast)|Plasma Decay Half-live (t1/2)|Area Under the Curve from Time Zero to Extrapolated Infinite Time (AUCinf)|Apparent Volume of Distribution (Vz/F)|Accumulation Ratio (Rac)|Apparent Oral Clearance (CL/F)|Apparent Oral Clearance of Study Drug (CLss/F)|Area under the curve at steady state under a dosing interval (AUCss,τ)|Maximum Observed Plasma Concentration at Steady State (Cmax,ss)|Time to reach maximum Observed Plasma Concentration at Steady State (Tmax,ss)|Minimum Observed Plasma Trough Concentration at Steady State (Cmin,ss)|Incident and titers of anti-body drug antibody against PF-07260437|Incident and titers of anti-body neutralizing antibody against PF-07260437|Number of participants with immune related adverse events at the recommended dose for expansion|Duration of response (DOR) in dose expansion|Time to progression (TTP) in dose expansion|Objective response rate (ORR) in dose expansion|Progression free survival (PFS)|Overall survival (OS) in the Expansion Cohorts (Part 2)|Phenotypes and quantity of tumor infiltrating lymphocytes (TIL) before and after PF-07260437 treatment All Phase 1 30 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment C4431001 October 17, 2023

Pharmaceuticals, F. (2022). A Trial to Compare the Ovarian Response of REKOVELLE and GONAL-F in Conventional Dosing in Women Undergoing Controlled Ovarian Stimulation.
	No Results Available Drug: REKOVELLE (Follitropin Delta)|Other: GONAL-F (Follitropin Alfa) Number of oocytes retrieved|Number of follicles (total) at end-of-stimulation|Size of the follicles at end-of-stimulation|Serum concentrations of estradiol at end-of-stimulation|Serum concentrations of progesterone at end-of-stimulation|Number of fertilized oocytes|Fertilization rate|Number of Blastocysts and Number of Good Quality Blastocysts|Total gonadotropin dose|Number of stimulation days|Proportion of subjects with early ovarian hyperstimulation syndrome (OHSS) (overall and by grade) and/or preventive interventions for early OHSS Female Phase 3 300 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 000401 April 15, 2024

Pharmaceuticals, F. and I. plc (2021). FP-101 Versus Placebo in the Treatment of Menopausal Vasomotor Symptoms.
	No Results Available Drug: FP-101 Change in the frequency (average daily number) of moderate-to-severe hot flashes.|Change in the severity (average daily rating) of moderate-to-severe hot flashes.|Change in nighttime awakenings (average daily number) with or without night sweats.|Evaluate the clinical meaningfulness of VMS changes after 1-week of treatment. Female Phase 2 105 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment 2021-FERV July 31, 2023

Pharmaceuticals, N. and Novartis (2021). Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected.
	No Results Available Drug: Alpelisib|Drug: Olaparib|Drug: Paclitaxel|Drug: Pegylated liposomal doxorubicin (PLD) Progression Free Survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment using RECIST 1.1 criteria|Overall survival|Number of participants with dose interruptions and dose reductions|Dose intensity|Time to definitive deterioration of the Eastern Cooperative Oncology Group (ECOG) performance status (PS)|Overall Response Rate (ORR) with confirmed response based on BIRC assessment according to RECIST 1.1 criteria|Clinical benefit rate (CBR) with confirmed response based on BIRC assessment according to RECIST 1.1|Time to response (TTR) based on BIRC assessment and according to RECIST 1.1|Duration of response (DOR) with confirmed response based on BIRC assessment and according to RECIST 1.1|Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of alpelisib and olaparib|Area under the curve from time zero to the last measurable concentration sampling time (AUClast)of alpelisib and olaparib|Maximum Concentration (Cmax) of alpelisib and olaparib|Time to reach maximum concentration (Tmax) of alpelisib and olaparib|Change from baseline in Function Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O TOI) All Phase 3 358 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CBYL719K12301|2019-004682-40 January 31, 2026

Pharmaceuticals, N. and Novartis (2022). A Study of Safety and Efficacy of KFA115 Alone and KFA115 in Combination With Tislelizumab in Patients With Select Advanced Cancers.
	No Results Available Drug: KFA115|Drug: tislelizumab Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only)|Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with tislelizumab (dose escalation only)|Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)|Frequency of dose interruptions, reductions|Dose intensity|Best overall response (BOR) per RECIST v1.1|Progression free survival (PFS) per RECIST v1.1|Duration of response (DOR) per RECIST v1.1|Time to progression (TTP) per RECIST v1.1|Area under the concentration time curve (AUC) of KFA115 or tislelizumab|Peak plasma or serum concentration (Cmax) of KFA115 or tislelizumab|Minimum plasma or serum concentration (Cmin) of KFA115 or tislelizumab|Time to reach peak plasma or serum concentration (Tmax) of KFA115 or tislelizumab|Elimination half-life (T1/2) of KFA115 or tislelizumab|The number of participants with anti-drug antibodies (ADA) All Phase 1 220 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CKFA115A12101 February 20, 2026

Philipson, A., et al. (2023). "The Cost-Effectiveness of a Dance and Yoga Intervention for Girls with Functional Abdominal Pain Disorders." PharmacoEconomics - open 7(2): 321-335.
	Background: Functional abdominal pain disorders (FAPDs) affect children worldwide, being more prevalent among girls. The individual and societal burdens of the disease are substantial, and evidence-based interventions are needed. Non-pharmacological treatments have generally produced promising results, with dance and yoga specifically having potential as an effective treatment option. Beside efficacy, the cost-effectiveness of interventions is important when prioritizing and allocating public resources. Objective(s): This study evaluated the cost-effectiveness of an 8-month dance and yoga intervention for girls with functional abdominal pain or irritable bowel syndrome, based on a randomized control trial called 'Just in TIME'. Method(s): The intervention, performed in Sweden, was studied using a decision analysis tool, i.e., a decision tree within the trial followed by a Markov model with a time horizon of 10 years. The base case considered healthcare costs as well as productivity losses, measuring the effects in gained quality-adjusted life-years (QALYs) and presenting an incremental cost-effectiveness ratio (ICER). Result(s): The base case results show that the intervention, compared with current practice, was the dominant strategy from both the 12-month and long-term perspectives. The sensitivity analyses indicated that the long-term, but not the short-term, findings were robust for different assumptions and changes in parameter estimates, resulting in ICERs similar to those of the base case scenario. Conclusion(s): Offering dance and yoga to young girls with FAPDs generates small QALY gains and monetary savings compared with standard healthcare and is likely cost-effective. These findings make a valuable contribution to an area where evidence-based and cost-effective treatment interventions are needed. Clinical Trials Registration Number: ClinicalTrials.gov identifier: NCT02920268; Name: Just in TIME-Intervention With Dance and Yoga for Girls With Recurrent Abdominal Pain.Copyright © 2023, The Author(s).

Phimarn, W., et al. (2019). "Efficacy of prasaplai for treatment of primary dysmenorrhea: A meta-analysis." Research Journal of Pharmacognosy 6(1): 71-80.
	Prasaplai is used in Thai traditional medicine for treatment of primary dysmenorrhea; however, clinical evidence is limited regarding the efficacy of Prasaplai for primary dysmenorrheal outcomes. This study has constituted a systematic review and meta-analysis to evaluate Prasaplai as an effective treatment for primary dysmenorrhea. Randomized controlled trials were retrieved and identified through electronic searches (PubMed, CINAHL, Cochrane Central Register of Controlled Trials, SCOPUS, Science Direct, and ThaiLis publications until May 2017). A hand search for relevant trials was also conducted. Quality of the selected trials was assessed using Jadad's scoring and A Cochrane Risk of Bias Assessment Tool. Studies were recruited for the meta-analysis if 1) they were randomized controlled trials, 2) participants were diagnosed with primary dysmenorrhea, and 3) a pain score was included. Related outcomes and adverse events were also evaluated for all groups. Four randomized controlled trials met the criteria, totaling 460 participants. Results revealed that Prasaplai significantly improved pain scores. The pooled mean difference was -1.24 (95% CI -1.90 to -0.59; p = 0.0002). The results did not indicate significant effects of Prasaplai on menstrual characteristics and associated symptoms, compared with NSAIDs; however, participants receiving Prasaplai reported a low frequency of adverse effects compared to the NSAID group. Current evidence suggests that Prasaplai improved pain associated with primary dysmenorrhea. Prasaplai had no effect on menstrual characteristics and associated symptoms. Additional rigorously-designed trials with larger sample sizes are warranted to confirm the effects of Prasaplai on primary dysmenorrhea and related outcomes.Copyright © 2018. Open access. All rights reserved.

Phuong, H., et al. (2021). "A meta-analysis of personalized embryo transfer (pET) based on the endometrial receptivity array (ERA)." PROSPERO International prospective register of systematic reviews.
	
Piasecki, A., et al. (2024). "High-frequency, high-intensity transcutaneous electrical nerve stimulation compared with opioids for pain relief after gynecological surgery: a systematic review and meta-analysis." Scandinavian Journal of Pain 24(1).
	OBJECTIVES: Opioids are important for postoperative analgesia but their use can be associated with numerous side effects. Transcutaneous electrical nerve stimulation (TENS) has been used for acute pain treatment and has dose-dependent analgesic effects, and therefore presents an alternative to intravenous (iv) opioids for postoperative pain relief. The aim of this meta-analysis was to compare high-frequency, high-intensity (HFHI or intense) TENS to iv opioids with regard to postoperative pain intensity, recovery time in the Post Anesthesia Care Unit (PACU) and opioid consumption after elective gynecological surgery. METHODS: We searched Medline, Embase, Web of Science, Cochrane, Amed and Cinahl for RCTs and quasi-experimental studies (2010-2022), and WHO and ClinicalTrials.gov for ongoing/unpublished studies. Meta-analysis and subsequent Trial Sequential Analysis (TSA) was performed for all stated outcomes. Quality of evidence was assessed according to GRADE. RESULTS: Only three RCTs met the inclusion criteria (362 participants). The surgical procedures involved surgical abortion, gynecologic laparoscopy and hysteroscopy. The applied TENS frequency was 80 Hz and intensity 40-60 mA. There was no difference in pain intensity according to Visual Analogue Scale (VAS) at discharge from PACU between the TENS and opioid group (MD VAS -0.15, 95 % CI -0.38 to 0.09) (moderate level of evidence). Time in PACU was significantly shorter in the TENS group (MD -15.2, 95 % -22.75 to -7.67), and this finding was manifested by TSA (high-level of evidence). Opioid consumption in PACU was lower in the TENS group (MD Morphine equivalents per patient mg -3.42, 95 % -4.67 to -2.17) (high-level of evidence). CONCLUSIONS: There was no detectable difference in postoperative pain relief between HFHI TENS and iv opioids after gynecological surgery. Moreover, HFHI TENS decreases recovery time and opioid consumption in PACU. HFHI TENS may be considered an opioid-sparing alternative for postoperative pain relief after gynecological surgery. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021231048.

Piccioni, M. G., et al. (2020). "Does hysterosalpingo-foam sonography have any therapeutic effect? A systematic review." Minerva Ginecol. 72(1): 55-58.
	INTRODUCTION: Tubal patency is one of the mandatory and necessary conditions to be granted in order to guarantee a good pregnancy rate. Numerous studies have been conducted to compare the various testing techniques for tubal evaluation in order to optimize the diagnostic-therapeutic process. Aim of this review is to clarify if hysterosalpingo-foam sonography could be considered as a useful tool not only in the diagnostic procedure, but also in treatment of infertility. EVIDENCE ACQUISITION: We performed a comprehensive search of relevant studies from January 2010 to December 2019 to ensure all possible studies were captured. A systematic search of PubMed databases was conducted. EVIDENCE SYNTHESIS: Over the years, increasingly less invasive approaches have been used to test tubal patency. For many years Laparoscopic with chromopertubation (DLS) has been considered the reference standard, then less invasive procedures have been introduced, such as hysterosalpingography (HSG). Sonohysterosalpingography (HyCoSy) represents a non-invasive procedure with accuracy comparable to HSG. Several studies have been made on different contrast agents that could be used on this procedure and recent studies considered hysterosalpingo-foam sonography (HyFoSy) procedure as a new technique used for the study of tubal function performed on unfertile women. Nowadays, HyFoSy is largely used in the study of tubal patency, but it is not completely clear the role of this technique as treatment of imperviousness of Fallopian tubes, leading to an increase in pregnancy rate after its use. CONCLUSIONS: As described in the literature for other procedures, similarly with HyFoSy, the tubal flushing improves the chance of an embryo implanting and establishing a spontaneous pregnancy. More prospective studies should be taken to better analyze the singular maternal risk fators, hoping to offer more complete indications to recommend HyFoSy.

Piekarska, K., et al. (2023). "Pro- and anti-inflammatory cytokines and growth factors in patients undergoing in vitro fertilization procedure treated with prednisone." Frontiers in Immunology 14: 1250488.
	Embryo implantation is a key moment in pregnancy. Abnormal production of pro- and anti-inflammatory cytokines, their receptors and other immune factors may result in embryo implantation failure and pregnancy loss. The aim of this study was to determine the profile of selected pro- and anti-inflammatory factors in the blood plasma of patients undergoing in vitro fertilization (IVF) and control women who achieved pregnancy after natural conception. The examined patients were administered steroid prednisone. We present results concern the plasma levels of IFN-, BDNF, LIF, VEGF-A, sTNFR1 and IL-10. We found that IVF patients receiving steroids differed significantly from patients who were not administered such treatment in terms of IFN-gamma and IL-10 levels. Moreover, IVF patients differed in secretion of all tested factors with the fertile controls. Our results indicated that women who secrete at least 1409 pg/ml of sTNFR1 have a chance to become pregnant naturally and give birth to a child, while patients after IVF must achieve a concentration of 962.3 pg/ml sTNFR1 in blood plasma for successful pregnancy. In addition, IVF patients secreting VEGF-A above 43.28 pg/ml have a greater risk of miscarriage or a failed transfer in comparison to women secreting below this value. In conclusion, fertile women present a different profile of pro- and anti-inflammatory cytokines, and growth factors compared to patients with recurrent implantation failure (RIF).Copyright © 2023 Piekarska, Dratwa, Radwan, Radwan, Bogunia-Kubik and Nowak.

Pignata, S., et al. (2023). "Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial." Gynecologic Oncology 172: 121-129.
	Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment.; Methods: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability.; Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected.; Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.; Competing Interests: Declaration of Competing Interest Sandro Pignata: Honoraria from AstraZeneca, Merck Sharp & Dohme (MSD), Roche, Pfizer, GlaxoSmithKline (GSK) and Clovis Pharma; and research funding from Roche, MSD, AstraZeneca and Pfizer. Amit Oza: Principal investigator of investigator-initiated studies with AstraZeneca; institutional grant funding from AstraZeneca; and steering committee member (non-compensated) for AstraZeneca, Clovis Oncology and GSK. Geoff Hall: Research funding from IQVIA. Beatriz Pardo: Research funding from AstraZeneca, GSK, Clovis and MSD. Radoslaw Madry: Advisory board participation for AstraZeneca, Roche and GSK; and personal fees from AstraZeneca, Roche and GSK. David Cibula: Advisory board participation for AstraZeneca, Roche, Genmab, SOTIO, Merck and GSK. Jaroslav Klat: Reports no disclosures. Ana Montes: Reports no disclosures. Rosalind Glasspool: Principal investigator for trials sponsored by AstraZeneca, Clovis, Tesaro, Immunogen, Pfizer and Lilly; research funding from Clovis, Boehringer Ingelheim and Lilly/Ignyta; institution research funding from Tesaro; institutional fees from Novartis and personal fees from AstraZeneca, MSD, Clovis, Tesaro, GSK, Immunogen and SOTIO. Nicoletta Colombo: Personal fees from AstraZeneca, MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, BIODCAD and Immunogen. Imre Pete: Reports no disclosures. Ana Herrero Ibáñez: Consulting/advisory board participation for GSK; speakers’ bureau participation for Clovis, GSK, MSD and PharmaMar; and research funding from AstraZeneca and Roche. Margarita Romeo Marín: Institution research funding from AstraZeneca, GSK, Clovis and Pfizer. Personal fees from MSD and GSK. Rumya Ilieva: Reports no disclosures. Constanta Timcheva: Principal investigator of clinical trials of AstraZeneca, Roche, Novartis, Pfizer and Merck; and member of advisory boards of Astellas, Servier and Novartis. Massimo Di Maio: Principal investigator of clinical trials of Roche, Merck, BeiGene, Novartis, Pfizer and Exelixis; member of advisory boards of AstraZeneca, Roche, Novartis, Pfizer, Eisai, Astellas, Janssen, Merck and Amgen; institutional research funding from Tesaro – GlaxoSmithKline. Christopher Blakeley: AstraZeneca employment and stock ownership. Rosie Tayl r: AstraZeneca contractor. Alan Barnicle: AstraZeneca employment and stock ownership. Andrew Clamp: Research funding from AstraZeneca; and honoraria from AstraZeneca, Clovis Oncology, GSK/Tesaro and Eisai. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pilegaard, S. P., et al. (2023). "Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial." Human reproduction (Oxford, England) 38(11): 2175-2186.
	STUDY QUESTION: Is the psychosocial wellbeing affected in women and men shortly after allocation to a freeze-all strategy with postponement of embryo transfer compared to a fresh transfer strategy? SUMMARY ANSWER: In general, psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) was similar in women and men allocated to a freeze-all versus those allocated to a fresh-transfer strategy 6 days after disclosure of treatment strategy (i.e. 4 days after oocyte retrieval), although women in the freeze-all group reported a slightly higher degree of depressive symptoms and mood swings compared to women in the fresh transfer group. WHAT IS KNOWN ALREADY: The use of a freeze-all strategy, i.e. freezing of the entire embryo cohort followed by elective frozen embryo transfer in subsequent cycles has increased steadily over the past decade in assisted reproductive technology (ART). This strategy essentially eliminates the risk of ovarian hyperstimulation syndrome and has proven beneficial regarding some reproductive outcomes in subgroups of women. However, patients experience a longer time interval between oocyte retrieval and embryo transfer, hence a longer time to pregnancy, possibly adding additional stress to the ART treatment. So far, little focus has been on the possible psychosocial strains caused by postponement of embryo transfer. STUDY DESIGN, SIZE, DURATION: This is a self-reported questionnaire based sub-study of a multicentre randomized controlled trial (RCT) including 460 women and 396 male partners initiating their first, second, or third treatment cycle of invitro fertilisation or intracytoplasmic sperm injection (ICSI) from May 2016 to September 2018. This sub-study was included in the primary project protocol and project plan for the RCT, as psychosocial wellbeing was considered a secondary outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women from eight public fertility clinics in Denmark and Sweden and one private clinic in Spain were randomized in a 1:1 ratio on the day of inclusion (menstrual cycle day 2 or 3) to either a freeze-all strategy with postponement of embryo transfer to a subsequent modified natural menstrual cycle or a fresh transfer strategy with embryo transfer in the hormone stimulated cycle. Treatment allocation was blinded until the day of the ovulation trigger. Women and their male partners were asked to complete a validated self-reported questionnaire 6 days after unblinding of treatment group allocation, corresponding to 4 days after oocyte retrieval, investigating their psychosocial wellbeing related to the treatment defined as emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit. The questionnaire included items from the Copenhagen Multi-Centre Psychosocial Infertility (COMPI) Fertility Problem Stress Scales and the COMPI Marital Benefit Measure. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were comparable between the two groups for both women and men. In total, response rates were 90.7% for women and 90.2% for men. In the freeze-all group, 207 women and 179 men completed the questionnaire compared with 204 women and 178 men in the fresh transfer group. Men in the two treatment groups did not differ in any of the explored aspects of psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) 6 days after disclosure of treatment strategy. Women in the freeze-all group reported a slightly higher degree of depressive symptoms (P = 0.045) and mood swings (P = 0.001) (i.e. variables included in 'emotional reactions to treatment') compared to women in the fresh transfer group. When adjusted for multiple testing, depressive symptoms were no longer significantly different between the two groups. No additional differences in psychosocial wellbeing were found. Self-reported quality-of-life during treatment was also rated as similar between the two groups in both women a d men, but was slightly lower than they would rate their quality-of-life when not in fertility treatment. LIMITATIONS, REASONS FOR CAUTION: Although response rates were high, selection bias cannot be excluded. As this study was an RCT, we assume that psychosocial characteristics of the participants were equally distributed in the two groups, thus it is unlikely that the identified psychosocial differences between the freeze-all and fresh transfer group were present already at baseline. Furthermore, the questionnaire was completed as a one-time assessment 4 days after oocyte retrieval, thus not reflecting the whole treatment process, whereas an assessment after the full completed treatment cycle is needed to draw firm conclusions about the psychosocial consequences of the whole waiting period. However, a question posted that late would be highly biased on whether or not a pregnancy had been achieved. WIDER IMPLICATIONS OF THE FINDINGS: The results indicate that individuals in the freeze-all group exhibited slightly higher levels of depressive symptoms and mood swings compared to those in the fresh transfer group. Nevertheless, it is important to note that any worries related to potential emotional strains stemming from delaying embryo transfer should not overshadow the adoption of a freeze-all approach in cases where it is clinically recommended. As long as patients are provided with comprehensive information about the treatment strategy before initiating the process, it is worth emphasising that other aspects of psychosocial wellbeing were comparable between the two groups. STUDY FUNDING/COMPETING INTEREST(S): The study is part of the Reprounion collaborative study, co-financed by the European Union, Interreg V Öresund-Kattegat-Skagerrak. L.P. reports financial support from Merck A/S. H.S.N. reports grants from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordic Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond and Independent Research Fund Denmark and personal fees from Ferring Pharmaceuticals, Merck A/S, Astra Zeneca, Cook Medical, IBSA Nordic and Gedeon Richter. H.S.N is founder and chairman of the Maternity Foundation and co-developed the Safe Delivery App (non-profit). N.C.F. reports grants from Gedeon Richter, Merck A/S, Cryos International and financial support from Ferring Pharmaceuticals, Merck A/S and Gedeon Richter. N.C.F. is chairman in the steering committee for the guideline groups for The Danish Fertility Society (non-profit). P.H. reports honoraria from Merch A/S, IBSA Nordic and Gedeon Richter. A.L.M.E. reports grants and financial support from Merck A/S and Gedeon Richter. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and personal fees from Preglem S.A., Novo Nordic Foundation, Ferring Pharmaceuticals, Gedeon Richter, Cryos International, Merch A/S, Theramex and Organon and the lend of embryoscope to the institution from Gedeon Richter. All other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02746562.

Pineda Mateo, M. and M. A. d. l. Cruz (2023). "Surgical management of endometrioma in patients with reproductive desire." Clín. investig. ginecol. obstet. (Ed. impr.) 50(2): [100851]-[100851].
	Endometriosis is a syndrome characterized by the presence of ectopic endometrial tissue. Endometrioma is its most common form of presentation, especially in moderate and severe stages of the disease.The objective of this work was to conduct a review of the surgical treatment of endometrioma through an updated literature search, which included 56 articles.In women with endometrioma, the ovarian reserve decreases and surgical techniques cause further reduction. Ovarian cystectomy is the technique of choice for the treatment of endometrioma. Sclerotherapy should be considered in recurrent endometriomas where ovarian preservation is relevant. Other techniques, such as CO2 laser vaporization or plasma ablation, show promising results in terms of recurrence and preservation of ovarian tissue. However, the management of endometrioma remains a challenge in reproductive medicine, where an individualized approach is essential.(AU)

Pineles, B. L., et al. (2023). "Ambulation for latency during expectant management of preterm prelabor rupture of membranes: a randomized controlled trial (AMBLE)." American Journal of Obstetrics & Gynecology MFM 6(1): 101218.
	BACKGROUND: Individuals hospitalized with preterm prelabor rupture of membranes are often advised to limit their activity or adhere to bed rest. Some evidence suggests that greater activity is associated with longer latency and improved outcomes, but no high‐quality evidence from a randomized controlled trial exists. OBJECTIVE: This study aimed to evaluate whether encouragement to ambulate at least 2000 steps daily affects latency among individuals with preterm prelabor rupture of membranes compared with usual care. STUDY DESIGN: This was a multisite unblinded, 2‐arm randomized trial of individuals at 23 0/7 to 35 0/7 weeks of gestation undergoing inpatient expectant management of preterm prelabor rupture of membranes with planned delivery at least 7 days away. Each participant wore a Fitbit Inspire that tracked steps. The intervention arm was encouraged (verbal and Fitbit‐based reminders) to reach a goal of 2000 steps per day. The usual‐care arm was allowed ad libitum activity with no step goal or reminders. The primary outcome was latency (days) from randomization to delivery. Secondary analyses included composite neonatal and maternal clinical outcomes and maternal mental health survey results. Statistical analyses were conducted with an intent‐to‐treat approach under a Bayesian framework using neutral priors (a priori assumed 50:50 likelihood of longer latency in either arm). A total of 100 participants were required to have 80% power to demonstrate a 4‐day difference in latency with 75% certainty (Bayesian probability). RESULTS: Among 163 eligible individuals, 100 (61%) were randomized, and after loss to follow‐up, 95 were analyzed. Gestational age at randomization was 29 3/7 weeks (interquartile range, 26 2/7 to 31 5/7) in the intervention arm and 27 4/7 weeks (interquartile range, 25 4/7 to 29 6/7) in the usual‐care arm. Median step counts were 1690 per day in the intervention arm (interquartile range, 1031–2641) and 1338 per day in the usual‐care arm (interquartile range, 784–1913). Median days of latency were 9 days in the intervention arm (interquartile range, 4–17) and 6 days in the usual‐care arm (interquartile range, 2–14). The primary analysis indicated a 65% posterior probability that the intervention increased latency relative to usual care (posterior relative risk, 1.09; 95% credible interval, 0.70–1.71). The relative risk was 0.55 (95% credible interval, 0.32–0.82) for the composite neonatal adverse outcome, with 99% posterior probability of intervention benefit, and was 0.94 (95% credible interval, 0.72–1.20) for the composite maternal adverse outcome, with 70% posterior probability of intervention benefit. There was a 94% posterior probability of the intervention arm having a greater decrease in maternal stress score from baseline to before delivery compared with the usual‐care arm (mean arm difference, 3.24 points [95% credible interval, −7.23 to 0.79]). Adjustment for gestational age at randomization had minimal impact on secondary outcome results. CONCLUSION: Individuals with preterm prelabor rupture of membranes randomized to encouragement to ambulate had a longer latency to delivery and improved neonatal and mental health outcomes, with similar maternal clinical outcomes compared with usual care.

ping, l., et al. (2022). "Effects of sleeve gastrectomy on patients with obesity and polycystic ovary syndrome: a meta-analysis."
	
Ping, X., et al. (2021). "The effect of eHealth interventions on female pelvic floor dysfunction: A systematic review and meta-analysis."
	
Ping, Y., et al. (2022). "Can acupuncture improve sleep quality and anxiety among women during perimenopause?: A protocol for systematic review and meta-analysis." Medicine 101(2): e28449.
	Background: The decrease in estrogen levels during the perimenopausal period can cause women to have various symptoms such as insomnia, emotional anxiety, and even depression. Therefore, whether the green therapy of acupuncture can improve the sleep quality and anxiety of perimenopausal women has attracted more and more attention. The purpose of this systematic evaluation was to assess the efficacy of acupuncture on insomnia and anxiety in perimenopausal women.; Methods: We will search for clinical observational pilot studies or cohort studies of acupuncture for insomnia, anxiety, or depression included in PubMed, Cochrane Library, Embase, Web of science, China Knowledge Network (CNKI), Wanfang, VIP and China Biomedical Database (CBM), etc. The search period will be from the establishment of the database until November 2021. Two researchers will independently perform literature screening, data extraction, and quality assessment. Finally, data analysis will be performed using Revman and Stata software.; Results: The purpose of this study was to evaluate the effectiveness and safety of acupuncture therapy for the treatment of insomnia, anxiety, and depression in perimenopausal women.; Conclusion: This study will provide new evidence on the effectiveness and safety of acupuncture for the treatment of insomnia, anxiety, and depression in perimenopausal women, and provide additional options for clinicians and patients to improve insomnia and anxiety.; Registration Number: INPLASY2021120012.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pingarron, C., et al. (2021). "Ospemifene in clinical practice for vulvo-vaginal atrophy: results at 3 months of follow-up of use." Gynecological Endocrinology 37(6): 562‐566.
	Objective: To assess the effect of ospemifene 60 mg/day in vulvovaginal atrophy (VVA) in postmenopausal women under conditions of routine clinical practice after 3 months of follow‐up. Methods: The AYSEX study is a Spanish observational, prospective, and unicentric study in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, sexual health, dryness, dyspareunia, quality of life, and satisfaction with treatment were assessed at baseline and after three months using validated scales. Results: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, vaginal health index increased and vaginal pH, dryness, and dyspareunia decreased significantly (p <.0001). A significant improvement was observed in sexual function and quality of life. Conclusions: This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, and satisfaction with the treatment.

Pingarrón, C., et al. (2022). "Vaginal health, endometrial thickness and changes in bone markers in postmenopausal women after 6 months of treatment with ospemifene in real clinical practice." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(1): 78-82.
	Objective: To assess vaginal health, endometrial thickness, and changes in bone markers in postmenopausal women with vulvovaginal atrophy (VVA) treated with 60 mg/day of ospemifene under routine clinical practice.; Methods: The AYSEX study is a Spanish observational and prospective study performed in one center in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated continuously with ospemifene 60 mg/day for 12 months as an appropriate therapeutic option. This article refers to the 3- and 6-months analysis. Vaginal health was assessed by pH and using Vaginal Health Index (VHI) at baseline and 3 months later. Endometrial thickness, measured by vaginal ultrasonography, and bone resorption marker (CTx) were assessed at baseline and 6 months later.; Results: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, pH improved from 6.1 to 4.5 ( p < .0001), and VHI improved from 10 to 19 points ( p < .0001). The percentage of patients with VVA according to VHI decreased from 100% to 5.2% ( p < .0001). After 6 months, mean CTx levels decreased from 0.42 pg/ml at baseline to 0.37 pg/ml 6 months later ( p = .0018), and mean endometrial thickness changed from 2.24 to 2.15 mm ( p = .6066).; Conclusions: Up to date, this is the only prospective and observational study with ospemifene in routine clinical practice conditions and confirms the results previously reported from randomized controlled clinical trials, improving VVA, not increasing endometrial thickness, and decreasing CTx levels by exerting an anti-resorptive function.

Pingarrón, S., et al. (2022). "Long-term use of ospemifene in clinical practice for vulvo-vaginal atrophy: end results at 12 months of follow-up." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(7): 577-582.
	Objective: To assess the improvement in vulvovaginal atrophy (VVA) of postmenopausal women treated with oral ospemifene 60 mg/day under conditions of routine clinical practice after 12 months of follow-up.; Methods: The AYSEX study is a Spanish observational, prospective, and unicentric study in which five gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with oral ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, the most bothersome symptoms, sexual health, endometrial safety, bone resorption markers, bone densitometry, mammography, treatment satisfaction, and quality of life were assessed at baseline and after 12 months using appropriate scales.; Results: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, a significant improvement was observed in all domains of Vaginal Health Index. This improvement was maintained at month 12 and only one patient remained with vaginal atrophy. In addition, a significant improvement was observed in the most bothersome symptoms, sexual function, and quality of life. There was no significant change in endometrial thickness, mammography, and bone health during the 12 months of treatment.; Conclusions: This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, endometrial safety, and satisfaction with the treatment.

Pingarrón, S., et al. (2023). "Evaluation of the efficacy of an antioxidant combination for the modulation of metabolic, endocrine, and clinical parameters in patients with polycystic ovary syndrome." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 39(1): 2227277.
	Objective: To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, N -acetylcysteine, vitamin B 6 , and S -adenosyl-L-methionine) for the modulation of metabolic, endocrine, and clinical parameters in comparison with oral contraception in non-diabetic women newly diagnosed with polycystic ovary syndrome (PCOS).; Methods: This was a prospective, partially randomized, multicenter study in which non-diabetic women with PCOS were recruited under routine clinical practice conditions and distributed in three groups to receive the following regimen for 6 months: 1) antioxidant combination (MN group); 2) oral contraception (OC group); or 3) oral contraception and the antioxidant combination (MN + OC group). General recommendation of healthy diet and regular exercise was given to all patients. Metabolic, endocrine, clinical, and quality of life parameters were recorded at baseline and after 6 months of therapy.; Results: A total of 96 women with PCOS were included in the study. After 6 months of treatment, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) level was reduced only in the MN group, with a significant mean reduction of -0.92 points. Androstenedione was significantly reduced in all groups. Clinical parameters that significantly improved in all groups were hirsutism, acne, irregular menstruation, and quality of life, with no statistical differences between the groups.; Conclusions: This study showed that the antioxidant combination might be a suitable therapy for patients with PCOS when oral contraceptive is not indicated, because in all groups clinical parameters, irregular menstruation as well as androstenedione and quality of life were significantly improved with no statistical difference between groups.

Ping-Tao, T. and J. M. Yutaka (2021). "The association of improvement in menopausal symptoms by black cohosh extracts: a pairwise meta-analysis and network meta-analysis."
	
Pinheiro, R. L., et al. (2019). "Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis." Acta medica portuguesa 32(3): 219-226.
	INTRODUCTION: The risks of pregnancy in women of advanced maternal age are not consensual amongst studies. The aim of this metaanalysis was to determine whether women of advanced maternal age (≥ 35 years old) had worse obstetrical and perinatal outcomes than non- advanced maternal age women (20 - 34 years old) in singleton, naturally-conceived pregnancies. MATERIAL AND METHODS: We searched PubMed/ MEDLINE, IndexRMP and the Cochrane Database of Systematic Reviews. Ten studies were included according to the following criteria: population of > 1000 nulliparous and/or multiparous women with singleton gestations who did not undergo any type of infertility treatment. Using Review Manager v. 5.3, two meta-analysis were performed: one comparing the outcomes of 20 - 34-year-old vs 35 - 40-year-old women, and another comparing the outcomes of 35 - 40-year-old women vs > 40-year-old women. RESULTS: Women aged 35 - 40 years old were more likely to have > 12 years of education than 20 - 34 years old and > 40 years old women. Advanced maternal age women (35 - 40 and > 40 years old) were more likely to be overweight and having gestational diabetes and gestational hypertension. They were also more likely to undergo induced labour and elective caesarean deliveries. Furthermore, they had worse perinatal outcomes such as preterm delivery, low birthweight babies, higher rates of Neonatal Intensive Care Unit admission and worse Apgar scores. Advanced maternal age women had higher rates of perinatal mortality and stillbirth. DISCUSSION: Most authors present similar results to our study. Although the majority of adverse outcomes can be explained through the physio-pathological changes regarding the female reproductive apparatus that come with aging and its inherent comorbidities, according to the existing literature advanced maternal age can be an independent risk factor per se. In older pregnant women without comorbidities such as gestational hypertension or diabetes there are still worse obstetric and perinatal outcomes, which indicate that advanced maternal age is an independent strong risk factor alone. CONCLUSION: Advanced maternal age women are at a higher risk of adverse obstetrical and perinatal outcomes. In both comparisons, worse outcomes were more prevalent in the older group, suggesting that poorer outcomes are more prevalent with increasing age.

Pinsard, M., et al. (2023). "Comparison of early loosening vs delayed section of mid-urethral slings for postoperative voiding dysfunction." International Urogynecology Journal 34(3): 675-681.
	Introduction and hypothesis: Bladder outlet obstruction (BOO) is a common occurrence after midurethral sling (MUS) insertion and can result in acute or chronic urinary retention or de novo lower urinary tract symptoms (LUTS). However, the management of BOO after MUS is not standardised. The objective of this study was to compare two therapeutic strategies for suspected BOO after MUS. Method(s): Patients who had surgical revision for voiding dysfunction with a post-void residual (PVR) >=100 ml after MUS in five centres between 2005 and 2020 were included in a retrospective study. Patients were divided into two groups: early sling loosening (EL) vs delayed section/excision of the sling (DS). Result(s): Seventy patients were included: 38 in the EL group and 32 in the DS group. The postoperative complication rate was comparable in both groups (10.5% vs 12.5%; p = 0.99). At 3 months, the rate of withdrawal from self-catheterisation was similar in the two groups (92.1% vs 100%; p = 0.25) as was the PVR (57.5 vs 63.5 ml; p = 0.09). After a median follow-up of 9 months, there were significantly more patients with resolved voiding dysfunction in the EL group (63.2% vs 31.3%; p = 0.01). The rate of persistent/recurrent stress urinary incontinence (SUI) was higher in the DS group (21% vs 43.7%; p = 0.04). In multivariate analysis, the main predictive factor of recurrent SUI was DS (OR 2.87, 95% CI 1.01-8.60, p = 0.048). Conclusion(s): Early loosening of MUS in the case of postoperative voiding dysfunction offers better efficacy than DS of the sling, with a lower risk of recurrent/persistent SUI.Copyright © 2022, The International Urogynecological Association.

Pinto, T. M. and B. Figueiredo (2022). "Anxiety and depressive symptoms, and positive and negative couple interactions among postpartum mothers and fathers before and during the COVID-19 pandemic." Families, systems & health : the journal of collaborative family healthcare 41(2).
	INTRODUCTION: The negative impact of the COVID-19 pandemic on mental health and couples' relationships may be particularly higher in vulnerable groups, including mothers and fathers during the transition to parenthood. This study compared mental health symptoms and couples' relationship quality among parents who were at 6 months postpartum before or during the COVID-19 pandemic. METHOD: A sample of 109 primiparous mothers and fathers recruited before the COVID-19 pandemic were assessed at 6 months postpartum, before (n = 69) or during the COVID-19 pandemic (n = 40). Participants completed self-reported measures of anxiety and depressive symptoms, and couples' positive and negative interactions. RESULTS: Mothers and fathers assessed at 6 months postpartum during the COVID-19 pandemic reported more depressive symptoms and more couples' negative interactions than mothers and fathers assessed at 6 months postpartum before the COVID-19 pandemic. DISCUSSION: Findings suggested the COVID-19 pandemic may have negatively impacted the adjustment of postpartum parents, but causality cannot be determined from these cross-sectional analyses. The COVID-19 pandemic may be an adverse condition for parents' postnatal mental health and couples' relationships. Findings contribute to the literature on the transition to parenthood by providing evidence on the burden that the COVID-19 pandemic can add to the already stressful experiences associated with the postpartum period. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pio, L., et al. (2023). "Ovarian-sparing surgery for ovarian tumors in children: A systematic review and meta-analysis." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49(10): 106923.
	Introduction: An increased number of children and adolescents with ovarian tumors have been managed with ovarian-sparing surgery in the last few years. However, comprehensive data on fertility outcomes and local relapse are scarce. In this study, we systematically describe the contemporary outcomes of ovarian-sparing surgery, as reported in the literature.; Materials and Methods: Using PRISMA guidelines, we analyzed studies reporting ovarian-sparing techniques for ovarian tumors in children and adolescents. from 1980 to 2022. Reports with fewer than three patients, narrative reviews, and opinion articles were excluded. Statistical analysis was performed for dichotomous and continuous variables.; Results: Of 283 articles screened, 16 papers (3057 patients) met inclusion criteria (15 retrospective/1 prospective) and were analyzed. The vast majority of studies had no long-term fertility follow-up data and direct comparison between ovarian-sparing surgery vs oophorectomy was reported in only a few studies. Ovarian sparing surgery was not associated with worse oncologic outcomes in terms of (i) tumour spillage or (ii) recurrence rates, and of key importance allowed a higher ovarian reserve at long term follow-up.; Conclusions: Ovarian-sparing surgery is a safe and feasible technique for benign tumors. Long-term outcome studies are needed to show efficacy and fertility preservation.; Competing Interests: Declaration of competing interest Luca Pio, Ahmed Abu-Zaid, Tarek Zaghloul, Huma F. Halepota, Andrew M. Davidoff, Paul D. Losty and Hafeez H. Abdelhafeez have nothing to disclose. (Published by Elsevier Ltd.)

Piovano, E., et al. (2024). "Implementing Enhanced Recovery After Surgery for hysterectomy in a hospital network with audit and feedback: A stepped-wedge cluster randomised trial." BJOG: An International Journal of Obstetrics and Gynaecology.
	Objective: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. Design(s): A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). Setting(s): Gynaecological units in the Piemonte region, Italy. Population: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. Method(s): Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). Main Outcome Measure(s): Length of hospital stay (LOS), without outliers (>98th percentile). Result(s): Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. Conclusion(s): Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.Copyright © 2024 John Wiley & Sons Ltd.

Piróg, M., et al. (2022). "GnRH Antagonist Protocol Enhances Coagulation During Controlled Ovarian Stimulation for IVF." Reproductive sciences (Thousand Oaks, Calif.) 29(12): 3521-3531.
	Changes in coagulation and fibrinolysis have been reported in women undergoing controlled ovarian hyperstimulation (COH) supporting a potential hypercoagulable condition related to this treatment. This study aimed at evaluating the changes in fibrin clot properties and thrombin generation induced by two different COH protocols: long with gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant). Primary outcomes included determination of plasma fibrin clot properties, including clot permeability (K s ) and efficiency of fibrinolysis using clot lysis time (CLT), along with thrombin generation (prothrombin fragments 1 + 2) and endogenous thrombin potential (ETP) and fibrinolysis inhibitor levels. One hundred twenty-nine infertile women were included in the final analysis. The GnRH-ant protocol resulted in increased ETP (+ 9.8%) and reduced K s (- 2.4%). Conversely, COH with the GnRH-a protocol reduced thrombin generation by decreasing both ETP (- 6.6%) and F1 + 2 (- 30.8%) together with favorably altered fibrin clot properties represented by increased K s (+ 21.7%) and reduced CLT (- 13.8%) as well as decreased PAI-1 levels (by 2.5 times). The GnRH-ant compared to the GnRH-a protocol increased PAI-1 levels (+ 77.3%), thrombin generation (9.3% higher ETP), and K s (+ 13.7%). In the GnRH-a group, post-COH K s was 14.3% higher (K s ≥ 7.92 × 10 -9 cm 2 ) in women with positive vs. negative pregnancy outcomes. Our results show that the GnRH-ant protocol enhanced thrombin generation and slightly decreased fibrin clot density. COH with the GnRH-a reduced thrombin generation and improved fibrin clot features. This trial was registered (NCT04166825). Clinical Trial Registration Number: NCT04166825. (© 2022. Society for Reproductive Investigation.)

Piróg, M., et al. (2021). "Fibrin clot properties among women with endometriosis and the impact of ovarian stimulation." Reproductive Biomedicine Online 43(1): 81-90.
	RESEARCH QUESTION: Is there a difference in fibrin clot phenotype in women with endometriosis before and after ovarian stimulation? DESIGN: Prospective study including 73 infertile women in two age-matched groups: (i) with confirmed endometriosis (n = 29); (ii) without endometriosis (n = 44). Assessments of plasma fibrin clot permeability (Ks), efficiency of fibrinolysis using clot lysis time (CLT), along with thrombin generation (prothrombin fragments 1+2 [F1+2] and endogenous thrombin potential [ETP]) and fibrinolysis inhibitors were performed together with clinical pregnancy rate. RESULTS: Endometriosis was associated with increased thrombin generation, reflected by both higher F1+2 (+96.1%, P = 0.005) and ETP (+14.2%, P = 0.014) along with unfavourably altered fibrin clot properties represented by lower Ks (-31%, P < 0.001) and prolonged CLT (+13.5%, P = 0.02), compared with the non-endometriosis group. Moreover, women with endometriosis had higher plasminogen activator inhibitor-1 (PAI-1; +272%, P = 0.004) concentrations and alpha-2-antiplasmin activity (+39.9%, P < 0.001) in contrast to the other group. Ovarian stimulation led to reduction in F1+2 (-48.1%, P < 0.001), improvement of fibrin clot phenotype reflected by higher Ks (+25.9%, P < 0.001) and shortened CLT (-11.9%, P < 0.001), along with lower PAI-1 (-54%, P = 0.016) compared with the baseline in women with endometriosis. CONCLUSIONS: Endometriosis is associated with the prothrombotic fibrin clot phenotype and increased thrombin generation. Ovarian stimulation favourably alters fibrin clot properties and leads to comparable pregnancy outcomes to those in women without endometriosis.

Piróg, M., et al. (2024). "Nonclassical congenital adrenal hyperplasia: Metabolic and hormonal profile." Clinical Endocrinology 100(2): 109-115.
	Objective: To investigate both metabolic and hormonal profiles of untreated women with nonclassical congenital adrenal hyperplasia (NCCAH). The secondary objective was to compare above profiles with polycystic ovary syndrome (PCOS) women and healthy controls.; Design: Retrospective, case-control study.; Patients: Women assigned to one of the groups: (1) NCCAH (n = 216), (2) PCOS (n = 221), (3) regularly menstruating (n = 216).; Measurements: Lipid profile including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol along with both fasting glucose (Glu) and insulin (Ins) levels and hormonal parameters were determined among all participants.; Results: Both NCCAH and PCOS women had higher body mass index in comparison to the controls (+7% and 18.9%, respectively). NCCAH women exhibited higher TC (+34.1%) and fasting glucose levels (+18.9%) together with elevated testosterone (60.2%), dehydroepiandrosterone sulphate (28.1%), free androgen index (91.9%) and antimüllerian hormone (58%) in comparison to healthy controls. PCOS group showed unfavourably altered metabolic profile reflected by higher TC (+35.4%), TG (+25%), fasting Glu (+22%), fasting Ins (+34.4%) along with homoeostatic model assessment for insulin resistance (HOMA-IR; 36.2%) in comparison to the controls. NCCAH women showed both lower insulin (-28.5%) and HOMA-IR (-31.8%) levels when compared to the PCOS.; Conclusions: NCCAH women showed less adversely altered metabolic profile than PCOS women, but not as favourable as in the healthy controls. Optimisation of screening for metabolic and reproductive health may help to initiate the treatment and improve treatment outcomes. (© 2023 John Wiley & Sons Ltd.)

Pitiyarachchi, O., et al. (2022). "What proportion of patients with stage 3 ovarian cancer are potentially cured following intraperitoneal chemotherapy? Analysis of the long term (≥10 years) survivors in NRG/GOG randomized clinical trials of intraperitoneal and intravenous chemotherapy in stage III ovarian cancer." Gynecologic Oncology 166(3): 410-416.
	Objective: Patients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS.; Methods: Data from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS.; Results: Of 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23-28%) and LTDFS ≥10 years was 18% (95% CI, 16-20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p < 0.001). Younger age (p < 0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis.; Conclusions: Approximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes.; Competing Interests: Declaration of Competing Interest MF reports honoraria from Astra Zeneca;GSK;Novartis;MSD;Takeda;Lilly;Eisei for advisory boards/consulting.Speaker fees from Astra Zeneca;GSK and MSD. Institutional research funding from Astra Zeneca;Novartis and Beigene. Travel expenses for Astra Zeneca. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Pittsburgh University, o., et al. (2023). Mindful Moms: Mechanisms of Mindfulness-based Cognitive Therapy During Pregnancy and Postpartum.
	The proposed study seeks to elucidate the mechanisms underlying Mindfulness-Based Cognitive Therapy in pregnancy to improve understanding of how and why this treatment modality enhances well-being, which can then be leveraged to optimize treatment for psychological distress emerging during this vulnerable period. Detailed Description Pregnancy and postpartum is a period of vulnerability for new or worsening psychiatric symptoms. Mindfulness Based Cognitive Therapy (MBCT) is an effective approach to mitigate pregnancy-related worsening of psychological distress. However, prior research has focused predominantly on symptoms of depression and anxiety, and is it not clear how or why MBCT improves psychological health during the perinatal period. Thus, the goals of this project are to (1) examine whether MBCT improves psychological functioning among pregnant women and whether these improvements persist at three-months postpartum, (2) examine whether improved ability to regulate emotions and behavior accounts for the beneficial effects of MBCT, and (3) determine what demographic, socioeconomic, and psychosocial factors impact treatment engagement and effectiveness. Show less

Piulats, R., et al. (2023). "A phase II trial of avelumab in combination with pegylated liposomal doxorubicin in recurrent/metastatic endometrial cancer (GEICO 70-E): analysis according to molecular classification." Annals of Oncology 34(Supplement 2): S519.
	Background: The Cancer Genome Atlas (TCGA) classified endometrial cancer (EC) into molecular subgroups with different prognosis and predictive value of response to immunotherapy or chemotherapy. Testing for surrogate biomarkers (BM) of TCGA groups may be clinically cost-effective. According to these BM groups, we evaluated differences in efficacy of avelumab (A) and pegylated liposomal doxorubicin (PLD) in recurrent EC pts. Method(s): Open-label, single-arm, multicenter, phase II study in recurrent/metastatic EC. Pts were treated with intravenous A 10 mg/kg (q2W) and PLD 40 mg/m2 (q4W). Primary endpoint was 6 months (m) progression free survival (PFS). Archival tumor tissue was collected for molecular classification according to BM of the TGCA groups. POLE mutations, mismatch repair markers (MMR) and p53 abnormalities were analysed to classify EC tumors. EC groups were as follows: POLE (POLE mutant); P53-ABN (POLE wt, p53 abnormal): MSI (microsatellite instability) (POLE wt, p53 wt, abnormal MMR); MSS (microsatellite stable) (POLE wt, p53 wt, normal MMR). Differences in PFS and overall survival (OS) were evaluated among BM groups. Result(s): BM analysis was performed in 41 pts: 26 (63.4%) were p53-ABN, 7 (17.1%) MSI, 7 (17.1%) non-specific molecular profile (NSMP), and 1 (2.4%) POLE. MSI/MSS classification showed 33 (80.5%) MSS tumors, 7 (17.1%) MSI, and 1 (2.4%) POLE. 6-m PFS was 45% [95% CI 31.9%-63.4%] with a median PFS of 5.68m [95% CI 3.58-7.98]. NSMP group showed the best PFS results: 6-m PFS, 66.7% and median, 9.2m (95% CI 1.7 - NR). 6-m PFS of MSI and P53-ABN groups was 28.6% and 42.3%, respectively. 6-m PFS was numerically better in MSS (46.9%) than in MSI (28.6%). Median OS time was 11.6m [95%CI; 7.4-NR] and 12-m OS was 47.5% [34.3%-65.8%]. Median OS in the NSMP, p53-ABN and MSI groups was 26.0m, 12.6m and 5.3m, respectively. OS was better in p53-ABN group than in MSI (HR: 3.44 [1.36; 8.69], p=0.01). OS was also better in MSS group than in MSI (HR: 3.78 [1.52; 9.43], p<0.01). Conclusion(s): A and PLD has activity in pre-treated recurrent EC. Pts with MSS and p53-ABN had better outcomes than those with MSI. Interestingly pre-treated NSMP pts show a median OS >2 y. Clinical trial identification: EudraCT number: 2018-000843-14. Legal entity responsible for the study: Grupo Espanol de Investigacion en Cancer de Ovario (GEICO). Funding(s): Pfizer. Disclosure: J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche, BMS, MSD, BeiGene, VCN, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS, Pfizer, Janssen, BeiGene, Mirati. I. Palacio Vazquez: Financial Interests, Personal, Advisory Role: AstraZeneca/MSD, GSK, Eisai; Financial Interests, Personal, Speaker's Bureau: AstraZeneca/MSD, GSK, Novartis, Bristol; Financial Interests, Personal, Other, Travel/Accomodations, expenses: MSD, GSK, PharmaMar. J.D. Alarcon: Financial Interests, Personal, Financially compensated role: GSK, Clovis, Roche, AstraZeneca/MSD; Financial Interests, Personal, Advisory Role: GSK, Clovis, AstraZeneca/MSD; Financial Interests, Personal, Speaker's Bureau: GSK, Clovis, Roche; Financial Interests, Personal, Expert Testimony: Clovis, GSK, AstraZeneca/MSD; Financial Interests, Personal, Other, Travel/Accomodations, expenses: GSK. M. Gil Martin: Financial Interests, Personal, Speaker's Bureau: Roche, AstraZeneca, PharmaMar; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other, Travel/Accomodations, expenses: PharmaMar/MSD, Clovis, GSK. L.M. Manso Sanchez: Financial Interests, Institutional, Funding: Clovis Oncology; Financial Interests, Personal, Research Grant: Tesaro/GSK; Financial Interests, Personal, Speaker, Consultant, Advisor: Tesaro/GSK, Pfizer, Novartis, AstraZeneca, Clovis Oncology, Eisai, Lilly, Pierre Fabre, Roche; Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Novartis, Roche, Pfizer, Lilly. S. Hernando Polo: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK, izer; Financial Interests, Personal, Speaker's Bureau: AstraZeneca, GSK, Pfizer; Financial Interests, Personal, Other, Travel/Accomodations, expenses: GSK. N. Ruiz: Financial Interests, Personal, Speaker's Bureau: GSK, AstraZeneca, Clovis. X. Matias-Guiu: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Lilly, GSK, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Clovis; Non-Financial Interests, Other, Consultancy: AstraZeneca. M. Romeo Marin: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Personal, Other, Travel/Accomodations, expenses: GSK, AstraZeneca/MSD. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Pivano, A., et al. (2022). "Enhanced recovery after posterior deep infiltrating endometriosis surgery: a national study." Fertility and Sterility 117(2): 376-383.
	Objective: To evaluate the impact of the implementation of a national enhanced recovery after surgery (ERAS) program for posterior deep infiltrating endometriosis (DIE) surgery on the length of hospital stay, the rate of postoperative complications, and readmission within 30 days.; Design: Comparative exposed/nonexposed observational study.; Setting: Study based on the French national medicoeconomic database of the Program of Medicalization of Information System.; Patients: Seven hundred and sixty-four women who underwent DIE surgery were involved and matched (1:3 ratio) into two groups: ERAS group for the year 2019 and non-ERAS group for the year 2015.; Interventions: Surgical management for posterior DIE.; Main Outcome Measures: The length of hospital stay, the rate of postoperative complications during the initial hospital stay, and readmission within 30 days.; Results: The ERAS group included 191 women, and the non-ERAS group included 573 women. The mean length of hospital stay was shorter in the ERAS group than in the non-ERAS group (4.28 ± 3.80 days vs. 5.42 ± 4.04 days, respectively). The rate of postoperative abdominal or pelvic pain syndromes was lower in the ERAS group than in the non-ERAS group (5/191 (2.62%) vs. 48/573 (8.38%), respectively; relative risk, 0.31 [0.125-0.7969]). The rate of postoperative complication and the rate of readmission within 30 days were not different between the two groups.; Conclusions: The implementation of ERAS has a significant positive impact on patient outcomes after DIE surgery. The length of hospital stay and abdominal or pelvic pain syndromes were reduced without increasing complications or readmission within 30 days. (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Pixiao, Z. and Z. Ying (2021). "Pelvic bone marrow sparing radiotherapy for cervical cancer: a systematic review and meta-analysis."
	
Pizarro, D., et al. (2023). "The Prognostic Significance of Tumor-Infiltrating Lymphocytes, PD-L1, BRCA Mutation Status and Tumor Mutational Burden in Early-Stage High-Grade Serous Ovarian Carcinoma-A Study by the Spanish Group for Ovarian Cancer Research (GEICO)." International Journal of Molecular Sciences 24(13).
	Early stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to determine the prognostic significance of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs), tumoral cell PD-L1 expression, BRCA mutational status and tumor mutation burden (TMB) in early-stage HGSOC. A retrospective study was performed on stage I and II HGSOC from the Molecular Reclassification of Early Stages of Ovarian Cancer (RECLAMO) cohort from the Spanish Group of Ovarian Cancer Research (GEICO). Centralized histological typing was performed based on morphological and immunohistochemical features. Intraepithelial (i) and stromal (s) CD8+ and CD4+ T cells and PD-L1 were evaluated on tissue microarrays by immunohistochemistry. BRCA1 and BRCA2 mutation status and TMB were analyzed in tumor DNA using next-generation sequencing. The study included 124 tumors. High iCD8+ (>20 TILs/core), low/intermediate CD4+ (<20 TILs/core) and high CD8+/CD4+ ratio (>35/core) were associated with favorable outcomes. Tumor cell PD-L1 expression (TPS ≥ 1) was present in only 8% of tumors. In total, 11 (16%) and 6 (9%) out of 69 HGSOC tested carried pathogenic or likely pathogenic BRCA1 or BRCA2 mutations, respectively. Median TMB of 40 tumors analyzed was 5.04 mutations/Mb and only 6 tumors had 10 or more mutations/Mb. BRCA status and TMB were not associated with TILs or prognosis. When compared with studies on advanced HGSOC, our results suggested that prognostic variables differed according to stage and that more studies focused on early stages of HGSOC are needed to better stratify these tumors.

Pkhaladze, L., et al. (2021). "Treatment of lean PCOS teenagers: a follow-up comparison between Myo-Inositol and oral contraceptives." European Review for Medical and Pharmacological Sciences 25(23): 7476-7485.
	OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder widely diffused and diagnosed in women of reproductive age. The pathology exhibits alteration of the reproductive functions, including conditions as hyperandrogenism, menstrual cycle irregularity, type 2 diabetes. These conditions are visible in the patients through phenotypical manifestations as hirsutism, acne, and obesity. Even if the syndrome is characterized by common features among both adult and adolescent women, the diagnostic criteria are different for the two age categories and to date still controversial. We investigated different treatments in PCOS adolescents with non-severe metabolic conditions, to evaluate which could be the appropriate therapeutical approach for these patients. PATIENTS AND METHODS: We enrolled lean teenagers with PCOS, and we divided the patients in two age ranges: 13-16 years old and 17-19 years old. They were treated for 3 months either with oral contraceptive pills (OCP) drospirenone/ethinylestradiol (group A), myo-Inositol (myo-Ins) (group B), or OCP plus myo-Ins (group C). Data were analyzed with a descriptive statistics summarizing quantitative variables including median, 25th and 75th percentiles. RESULTS: We pointed out that the group of 13-16 years old lean teenagers treated with myo-Ins exhibit a significant decrease of weight and body mass index (BMI), and an effective improvement the metabolic and hormonal parameters achieved with a non-pharmacological treatment. In the older teenagers aged 17-19 years, data highlights that myo-Ins treatment in combination with OCP prevents the increases of weight and BMI, improves the metabolic profile of the patients, and strongly ameliorates the hormonal parameters analyzed. CONCLUSIONS: The results indicate a different scenario in the two age ranges considered and interestingly suggest an important role of myo-Ins in the PCOS context. A therapy based on this natural compound alone or in combination with OCP seems effective to improve both metabolic and hormonal parameters of PCOS adolescents and thus could represent a novel and valid option to consider for the treatment of this syndrome.

Plana, A., et al. (2023). "Patient-Controlled Epidural Analgesia vs Intravenous Patient-Controlled Analgesia in early recovery and pain control in gynecologic cancer." Clinical Nutrition ESPEN 57: 789.
	Background: To examine early recovery and postoperative pain control in patients who undergo laparotomy for gynecological tumors in relation to epidural or intravenous analgesia. Method(s): A retrospective study including patients with suspected or diagnosed gynecological cancer to undergo laparotomy (n=411), undertaken between January 2020 and December 2021. Patients received either patient-controlled epidural analgesia (PCEA; n=355) with 0.5 mug/ml sufentanil and 2 mg/ml bupivacaine/ropivacaine, or IV-intravenous patient-controlled analgesia (PCA; n=56), with 1 mg/ml oxycodone for their analgesia. Following variables were examined: pain self-assessment (0-10) rating scale (NRS), postoperative days (PODs) until mobilisation, opioid usage, length of stay (LoS) and postoperative complications (Clavien-Dindo). Result(s): In total 86% of patients had PCEA whereas 16% of patients used IV-PCA. The pain control was superior for PCEA users. Of IV-PCA users, 8% were without pain compared to 30% in PCEA users at POD1(p<0.001). Patients having PCEA had less moderate pain compared to IV-PCA carriers POD1(6 vs 19%; p<0.001). PCEA users needed less supplementary i.v. opioids compared to IV-PCA users (18.3% vs 44.6%, p<0.001). LoS (p=0.015), duration of analgesia (p<0.001) and time with urinary catheter (p<0.001) were shorter for IV-PCA users. In 10.1% of cases with PCEA, complications occured. Due to nonsufficient action,17 of patients switched to IV-PCA. Other types single case patient meet complications were dura punction, severe neck pain, visual hallucinations, relieving pain in wrong area, muscle weakness, leakage of CSF, two cases of paresthesia, hypotension, leakage, faulty administration, allergy to epidural plaster and pruritus. IV-PCA had 1 complication (1.8%) because of mechanical problems. The physical recovery of the patients was faster in PCEA group and the number of patients walking POD1 was greater for PCEA (70% vs 55%, p=0.028). Patients not walking POD1 had longer surgeries (p<0.001), more blood loss (p<0.001), more often malignant tumors (p<0.001). They were also more often in advanced stages (p=0.021). Patients in advanced stages also had longer LoS, more blood loss and longer surgeries (p<0.001). Postoperative complications (Clavien -Dindo) between the two groups were not statistically different. However, C-D 4 and 5 were only present in the PCEA (1.4 and 0.6%) indicating the presence of more advanced stages and longer surgeries in the group. Conclusion(s): Patients with PCEA were in less pain, more likely to walk POD1 and used less supplementary IV opioids. The PCEA had a longer LoS and catheterisation time, however there are other factors that could explain this difference. A higher complication rate followed the PCEA, but no patients were seriously harmed. Risk groups for not walking POD1were patients with longer surgery times, more blood loss and those with more advanced disease, who were an overall vulnerable group for slower recovery.Copyright © 2023

Plante, M., et al. (2024). "Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer." The New England Journal of Medicine 390(9): 819-829.
	BACKGROUND: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHOD(S): We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of <=2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULT(S): Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P=0.048) and beyond 4 weeks (4.7% vs. 11.0%; P=0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001). CONCLUSION(S): In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.).Copyright © 2024 Massachusetts Medical Society.

Plassais, C., et al. (2023). "Retropubic tape surgery for stress urinary incontinence: can women be cured without voiding dysfunction?" World Journal of Urology 41(9): 2489-2494.
	PURPOSE: Retropubic tension free vaginal tape (RP-TVT) has become the gold standard for surgical management of female stress urinary incontinence but is associated with voiding dysfunction (VD). We developed for more than 10 years a reproductible and totally tension free tape procedure. Our goal is to determine efficiency of this technique compared to the incidence of VD. METHOD(S): We retrospectively reviewed patients who underwent RP-TVT in our center between 2011 and 2019. Subjective cure, VD (determined as maximum urinary flow rate (Qmax)<15 mL/s or post void residual (PVR) volume>150 mL, or tape's section or resection requirement for underactive bladder (UB) with significant PVR) was assessed at 1 year. The main objective was the evaluation of subjective cure and VD at 1 year. RESULT(S): On the 319 patients reviewed, 93% of the patients were dry and 10.9% presented VD at one year. UB (OR=5.01 [1.55-16.44], p=0.008), preoperative Qmax<15 mL/s (OR=0.89 [0.84-0.95], p=0.001) and previous incontinence surgery (OR=4.20 [1.54-11.46], p=0.005) were associated with VD. Acute urinary retention concerned 4.7% of the population and all were resolved after 6 weeks postoperatively. We reported 0.3% of de novo urgency and patients without VD showed a significant decrease of their voiding time at 1 year. CONCLUSION(S): The placement of RP-TVT without intraoperative tightening seems to be a safe technique ensuring a high cure rate and low occurrences of bladder outlet obstruction.Copyright © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Plaza, D., et al. (2023). "commerciallyComparison of the dose distribution of the VMAT radiotherapy technique depending on the beam used: FFF-X10MV and FFF-X15MV." Reports of Practical Oncology and Radiotherapy 28(5): 654-660.
	Background: The aim of the study was to answer the question of whether flattening filter (FF) and flattening filter-free (FFF) beams can be used alternately in the volumetric modulated arc therapy (VMAT) treatment technique, regardless of the size of the irradiated volume [small (S) or large (L) planning target volume (PTV)].Materials and methods: Two groups of patients were examined: a group with a S-PTV-laryngeal cancer and a group with a L-PTV - gynecological volume. For each patient, two treatment plans were made for beams (energies): FFF-X10MV and FF-X15MV. Then, a statistical analysis, nonparametric test, and independent groups were performed, comparing the beams' impact on the analyzed treatment plans. Result(s): In the case of laryngeal irradiation (S-PTV), there are no statistically significant differences between the energy used and the assessed parameters of the plan. In the case of gynecological volume (L-PTV), only statistically significant differences were noted for the number of monitor units depending on the energy used. For a large irradiated volume (gynecological case), the use of FFF beams increases the number of monitor units by 39,4% in relation to the FF beam. Conclusion(s): In the case of gynecological neoplasms, statistically significant differences were found in the number of monitor units. Therefore, in the case of irradiation of L-PTV, it is recommended that flattening-filtering beams are used due to the smaller number of monitors. In the case of S-PTV, no statistically significant differences were found between the types of beams used (FF or FFF) and the treatment plan parameters analyzed in the study.Copyright © 2023 Greater Poland Cancer Centre.

plc, N. (2023). NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours.
	No Results Available Drug: Fosifloxuridine Nafalbenamide|Drug: Leucovorin|Drug: Pembrolizumab|Drug: Docetaxel Number of patients tolerating dose levels (maximum tolerated dose; MTD) in each of the combinations|Number of patients reporting treatment-emergent adverse events (TEAEs) in each of the combinations|Number of patients achieving a reduction in tumour volume (Objective response rate; ORR) All Phase 1|Phase 2 91 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment NuTide:303|2022-000722-14 January 2025

Plotti, F., et al. (2020). "Tailoring parametrectomy for early cervical cancer (Stage IA-IIA FIGO): a review on surgical, oncologic outcome and sexual function." Minerva ginecologica.
	INTRODUCTION: Cervical cancer is currently one of the most common cancers afflicting the female population worldwide and in industrialized countries the presence of screening and a specific diagnostic and therapeutic process has favored early diagnosis of cervical cancer. In literature have found that reducing the radicality on the parametria in early cervical cancer (ECC), reduces complications without impacting oncological outcomes, but the data in the literature are not yet clear. EVIDENCE ACQUISITION: Searching on Pubmed we included 1473 articles from January 1974 to 2020. We identified all the studies that compared different type of radical hysterectomy in the primary surgical treatment of ECC. 16 articles were elected for the review. EVIDENCE SYNTHESIS: Modified radical hysterectomy (Piver II /Querleu-Morrow Type B) in ECC, if compared to CRH (Piver III / Querleu-Morrow Type C2), is not associated with worse cancer outcome and patient survival, but it is associated with a minor operating time, lower blood loss and minor bladder dysfunction. Nerve sparing radical hysterectomy approach (NSRH/ Querleu-Morrow Type C1) compared to CRH (Piver III / Type C2) in the ECC, with our data we can confirm a noninferiority regarding the oncological outcome. CONCLUSION(S): Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.

Plowden, T. C., et al. (2023). "Probability of Pregnancy with Mono vs Multiple Folliculogenesis in Women with Unexplained Infertility." Journal of the Endocrine Society 7(1): bvac142.
	Context: Ovarian stimulation (OS) increases pregnancy rates but can cause multiple folliculogenesis and multiple pregnancy. Objective(s): To determine whether the probability of pregnancy differs in OS cycles with mono-vs multifolliculogenesis in women with unexplained infertility (UI). Design(s): Secondary analysis of a multicenter, randomized controlled trial: Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation with 3 treatment arms: gonadotropins, clomiphene, or letrozole, combined with intrauterine insemination. Women were categorized as having either 1 or >= 2 mature follicles (>= 16mm). Relative risk (RR) and 95% CIs for clinical pregnancy and live birth by number of follicles were estimated using generalized linear models adjusted for age, body mass index, years of infertility, and history of prior live birth. Setting(s): 12 US-based clinical sites. Participant(s): Normally cycling women aged 18 to 40 years with a normal uterine cavity and at least 1 patent fallopian tube. Male partners with >= 5 million total motile sperm. Intervention(s): Gonadotropins, clomiphene, or letrozole with insemination Main Outcome Measure(s): Clinical pregnancy rates (CPR) and live birth rates (LBR). Result(s): A single mature follicle > 16mm resulted in lower CPR (RR, 0.70; 95% CI, 0.54-0.90) and LBR (RR, 0.67; 95% CI, 0.51-0.89) compared with >= 2 mature follicles. When stratified by treatment modality, no association of follicle number with CPR or LBR was observed for letrozole or clomiphene, but women using gonadotropins had lower CPR and LBR with monofolliculogenesis. Conclusion(s): In couples undergoing gonadotropin treatment for UI, monofolliculogenesis following OS is related to a lower rate of live birth.Copyright © 2022 Published by Oxford University Press on behalf of the Endocrine Society.

Pluym, I. D., et al. (2021). "1105 Edinburgh postnatal depression scores and postpartum healthcare utilization." American Journal of Obstetrics and Gynecology 224(2): S681‐S682.
	Objective: To investigate the association of antepartum Edinburgh Postnatal Depression Scores (EPDS) on postpartum healthcare utilization. Study Design: This was a secondary analysis of a randomized, non‐blinded trial comparing the timing of postpartum visits (PPV) in a single academic center. Prospective variables collected included demographics, delivery outcomes, postpartum visits to the emergency department (ED) and clinic and EPDS in the antepartum period and immediately postpartum prior to discharge from the hospital. Univariable receiver operating characteristics (ROC) curves and Spearman correlation were utilized. Multivariable logistic regression was performed to adjust for confounders of attendance at the clinic and ED. Results: Between November 2018 and March 2020, 256 patients were randomized, and outcome data are available for 250. The patient population had multiple underlying comorbidities, notably obesity (53%), diabetes (30%), mental health disorders (22%) and hypertensive disorders (21%). Eighteen women (7%) in the cohort utilized the ED within 30 days of delivery with the median attendance on postpartum day 10 (IQR 7.5‐20). An elevated antepartum EPDS score >10 was more common among patients who used the ED compared to those who did not (47% vs 17%, p=0.004) (Table 1) with an area under the curve (AUC) of 0.648. (Figure 1) Inpatient EPDS were not associated with postpartum ED usage. A consult with a social worker during the delivery hospitalization was more common among those who utilized the ED (72% vs 29%, p<0.001) and was the strongest predictor after adjusting for confounders (aOR 5.43 [1.38‐21.4]). There were no other demographic and clinical variables predictive of ED usage. Twenty one women (8%) presented to the clinic for an urgent postpartum visit and were more likely to have an antepartum EPDS >13 (31% vs 12%, p=0.027, aOR 7.93 [1.32‐47.7]) Conclusion: An elevated EPDS in the antepartum time period is associated with postpartum emergency department use and urgent clinic visits. Close postpartum follow‐up may be warranted for women with elevated EPDS during pregnancy. [Formula presented] [Formula presented]

Plymouth University, o., et al. (2021). Evaluating the Management of Chronic Pelvic Girdle Pain.
	No Results Available Device: customised pelvic support shorts|Other: Exercise|Other: advice Change from baseline pain intensity (Numerical Rating Pain Scale) at 24 weeks|Pelvic girdle questionnaire|EQ-5D-5L|SF36|EPDS|iciq-ui sf|Support shorts wear time|Health resource use questionnaire Female Not Applicable 24 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment 297938 February 4, 2023

Podzolkova, N. M., et al. (2022). "Efficacy of combination therapy in patients with deep infiltrating endometriosis." Voprosy Ginekologii, Akusherstva i Perinatologii 21(5): 105-112.
	Objective. To justify the choice of progestogen and to evaluate the effect of dienogest on the intensity of pelvic pain in patients after surgical treatment for deep infiltrating endometriosis. Patients and methods. This prospective comparative non-randomized study enrolled 39 women (mean age 31.2 +/- 2.7 years) after surgical treatment for deep infiltrating endometriosis. All patients were divided into two clinical groups. In the study group (n = 21), daily administration of 2 mg of dienogest (Zafrilla) was prescribed for 6 months; in the comparison group (n = 18), patients did not receive hormone therapy after surgical treatment. The gynecological examination, transvaginal pelvic ultrasound, magnetic resonance imaging, and pain assessment with a visual analogue scale (VAS) were performed before and 3 and 6 months after the treatment. Results. The main symptoms of endometriosis were dyspareunia in 79.49% (n = 31) of patients, dysmenorrhea in 71.79% (n = 28), pelvic pain in 64.10% (n = 25), intestinal pain in 61.54% (n = 24), and dysuria in 15.38% (n = 6). The use of dienogest for 6 months in the postoperative period led to a significant reduction in the severity of dysmenorrhea, pelvic pain, dyspareunia, and intestinal pain. In the study group, VAS scores at the beginning of the study were 8.3 +/- 1.4, after 3 months - 5.4 +/- 1.1, after 6 months - 1.6 +/- 0.8; in the comparison group - 8.2 +/- 1.1; 6.9 +/- 1.3 and 3.7 +/- 1.1, respectively (p <= 0.05). Conclusion. The use of Zafrilla (dienogest, 2 mg) in the postoperative period in deep infiltrating endometriosis is well tolerated and can significantly reduce pain intensity compared to surgery alone without hormone therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Poeira, A. F. and M. O. Zangão (2022). "Construct of the Association between Sleep Quality and Perinatal Depression: A Literature Review." Healthcare (Basel, Switzerland) 10(7).
	Pregnancy is characterized by hormonal and physiological changes; some of these changes cause changes in sleep, presenting excessive sleep in early pregnancy due to the action of progesterone, and difficulty sleeping at the end of pregnancy due to weight gain and frequency of urination. OBJECTIVE: to identify and systematize the evidence on the association between sleep quality and perinatal depression in pregnant and postpartum women. METHODS: an integrative literature review was carried out with a search in the CINAHL, MEDLINE, and SCOPUS databases using the PRISMA flowchart. RESULTS: Of the 92 articles, 10 studies were included according to the eligibility criteria. Results indicate that poor sleep quality during pregnancy is predictive of prenatal and postnatal depression. Sleep quality worsens with increasing gestational and maternal age. CONCLUSIONS: Sleep quality during pregnancy is associated with perinatal depression, a global public health problem with high prevalence. Due to its severe consequences for women, children, and families, perinatal depression needs to be identified early, preferably during pregnancy or soon after childbirth, justifying the priority of screening and prevention.

Pohjoranta, E., et al. (2024). "Pregnancy outcomes following routine early provision of intrauterine device after first-trimester induced abortion-A secondary analysis of a randomized controlled trial with a 5-year follow up." Acta Obstetricia et Gynecologica Scandinavica 103(2): 342-350.
	Introduction: Women undergoing an induced abortion are highly fertile and at risk of subsequent unplanned pregnancy. We recently completed a randomized clinical trial showing that routine provision of intrauterine device (IUD) at the time of abortion significantly reduced the risk of subsequent abortion during a 5-year follow up. As the use of highly effective contraception may affect all subsequent pregnancies, we analyzed the rate and distribution of all subsequent pregnancies (deliveries, miscarriages, and abortions), and the risk factors for these various pregnancy outcomes in the above-mentioned randomized clinical trial. Material(s) and Method(s): We enrolled adult women requesting first-trimester induced abortion and candidates for IUD for post-abortion contraception. Women (n = 751) were randomized to receive an IUD (either levonorgestrel-releasing IUD or copper IUD) by the clinic responsible for abortion care vs. routine care of IUD provision in primary health care with oral contraceptives for interval contraception. In the present secondary analysis, we identified all deliveries, miscarriages, and abortions in the intervention (n = 375) and control (n = 373) cohorts during the 5-year follow up using the Finnish national registries. The trial is registered at Clinical Trials (NTC01223521). Result(s): The overall delivery, miscarriage, and abortion rates were 42.0, 12.0 and 32.1/1000 years of follow up (yFU). Any new pregnancy occurred in 98 women in the intervention and in 129 women in the control cohort (hazard ratio 0.73, 95% confidence interval 0.56-0.95, p = 0.023). The effect of routine IUD provision in reducing pregnancies was limited to the first 2 yFU. The number of subsequent induced abortions and of women undergoing it were significantly reduced, and time to abortion was prolonged by the intervention. However, the overall number, the number of women with subsequent delivery or miscarriage, and the times to these events were not significantly affected. History of previous pregnancy (delivery or abortion) and smoking were risk factors for subsequent induced abortion, but not for delivery or miscarriage. Conclusion(s): Routine provision of IUD as part of abortion care did not reduce the rates of delivery or miscarriage during the 5-year follow up. The rates of all pregnancies and the need of subsequent induced abortion were reduced by IUD provision during the first 2 yFU.Copyright © 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Pohl, O., et al. (2022). "A model-based analysis to guide gonadotropin-releasing hormone receptor antagonist use for management of endometriosis." British journal of clinical pharmacology 88(5): 2359-2371.
	Aims: To identify linzagolix doses, an oral GnRH receptor antagonist, that effectively lower oestradiol (E2) to relieve endometriosis-related pelvic pain without compromising bone health.; Methods: Integrated statistical, pharmacokinetic-pharmacodynamic and systems pharmacology models were developed from Phase 1 and 2 clinical trial data in healthy volunteers and patients, receiving linzagolix 25-200 mg daily or placebo, and analysed simultaneously. The main outcome measures were pelvic pain scores for dysmenorrhoea, nonmenstrual pelvic pain (NMPP), uterine bleeding and lumbar spine bone mineral density (BMD).; Results: Linzagolix pharmacokinetics were described by a 2-compartment model with sequential zero/first-order absorption process (CL/F: 0.422 L/h). E2 changes over time were well described as a function of linzagolix 24-hour AUC (AUC 50 : 1.68 × 10 5 ng h/mL). For a Caucasian reference patient, a change in E2 from 50-20 pg/mL at 24 weeks increased the odds of relief of dysmenorrhoea 1.33-fold and NMPP 1.07-fold (95% CI: 1.22-1.47 and 1.02-1.12, respectively) and decreased bleeding days by 1.55 (95% CI: 1.39-1.72). A previously validated quantitative systems pharmacology BMD model was adjusted to the clinical data. The mean week 24 lumbar spine BMD change from baseline ranged from -0.092% in the 50 mg dose, -1.30% in the 100 mg dose group and -2.67% in the 200 mg dose group.; Discussion: The previously-reported E2 target range (20-50 pg/mL) to balance efficacy and safety endpoints was confirmed. Linzagolix once daily doses between 75-125 mg daily were expected to meet endometriosis-associated pain, efficacy, and BMD loss targets in Caucasian patients. (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Pokrzywinski, R. M., et al. (2021). "Responsiveness and thresholds for clinically meaningful changes in worst pain numerical rating scale for dysmenorrhea and nonmenstrual pelvic pain in women with moderate to severe endometriosis." Fertility and Sterility 115(2): 423-430.
	OBJECTIVE: To evaluate the utility, responsiveness, and thresholds for clinically meaningful change of a numerical rating scale for worst pain associated with dysmenorrhea (NRS-DYS) and nonmenstrual pelvic pain (NRS-NMPP) in women with moderate to severe endometriosis-associated pain. DESIGN: Analysis of data from two phase III randomized clinical trials (EM-I [NCT01620528] and EM-II [NCT01931670]). SETTING: Not applicable. PATIENT(S): Premenopausal women ages 18-49 years with moderate to severe endometriosis-associated pain. INTERVENTION(S): Participants in both trials were randomized 3:2:2 to receive placebo, elagolix 150 mg once daily, or elagolix 200 mg twice daily for 6 months. MAIN OUTCOME MEASURE(S): NRS-DYS and NRS-NMPP. RESULT(S): EM-I enrolled 871 women and EM-II enrolled 815 women. For patients with a global impression of improvement at month 3, the least-squares mean change between baseline and month 3 was -3.6 (EM-I and EM-II) for NRS-DYS and -1.9 (EM-I) and -2.0 (EM-II) for NRS-NMPP. Standard errors of measurement were 2.99 (EM-I) and 2.86 (EM-II) for NRS-DYS and 1.74 (EM-I) and 1.71 (EM-II) for NRS-NMPP. Baseline half standard deviations were 0.78 (EM-I) and 0.85 (EM-II) for NRS-DYS and 0.92 (EM-I) and 0.96 (EM-II) for NRS-NMPP. Based on these results, clinically meaningful changes were defined as a reduction of 4 points for NRS-DYS and 2 points for NRS-NMPP. CONCLUSION(S): This study demonstrated the utility and responsiveness of separate numerical rating scales to assess worst pain for dysmenorrhea and NMPP in women with moderate to severe endometriosis-associated pain and identified initial thresholds for clinically meaningful change.

Polasek, D., et al. (2023). "Nutritional interventions in treating menopause-related sleep disturbances: a systematic review." Nutrition reviews.
	Context: Sleep disturbances are a core symptom of menopause, which refers to the permanent cessation of menstrual periods. Nutritional interventions may alleviate menopause-related sleep disturbances, as studies have shown that certain interventions (eg, tart cherry juice, or tryptophan-rich foods) can improve relevant aspects of sleep.; Objective: The aim of this systematic review was to examine the effect of nutritional interventions for menopause-related sleep disturbances, in order to inform the subsequent development of specific interventional trials and assess their potential as a treatment for menopause-related sleep disturbances.; Data Sources: Published studies in English were located by searching PubMed and PsycArticles databases (until September 15, 2022).; Data Extraction: Following full-text review, a final total of 59 articles were included. The search protocol was performed in accordance with PRISMA guidelines.; Data Analysis: A total of 37 studies reported that a nutritional intervention improved some aspect of sleep, and 22 studies observed no benefit. Most (n = 24) studies recruited postmenopausal women, 18 recruited menopausal women, 3 recruited perimenopausal women, and 14 recruited women from multiple groups. The majority of the studies were of low methodological quality. Due to the heterogeneity of the studies, a narrative synthesis without meta-analysis is reported.; Conclusion: Despite the large heterogeneity in the studies and choice of intervention, the majority of the identified studies reported that a nutritional intervention did benefit sleep, and that it is mainly subjective sleep that is improved. More high-quality, adequately powered, randomized controlled trials of the identified nutritional interventions are necessary.; Systematic Review Registration: PROSPERO registration no. CRD42021262367. (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Polgár, C., et al. (2022). "[Radiotherapy and radio-chemotherapy of cervical cancer]." Magyar onkologia 66(4): 307-314.
	Radiotherapy has a significant role in the management of cervical cancer. Radiotherapy is indicated in two-thirds of all cervical cancer patients. Indications of radiotherapy are based on level I-II evidences in the vast majority of cases, although in some cases the use of radiotherapy is supported by the results of retrospective clinical trials. In this review, indications of curative and palliative irradiation and radio-chemotherapy are summarized and technological advances of contemporary external beam radiotherapy and brachytherapy are presented.

Pollack, B. L., et al. (2022). "Impact of permanent versus absorbable suture in vaginal suspension surgery for apical pelvic organ prolapse." American Journal of Obstetrics and Gynecology 226(3 Supplement): S1281-S1282.
	Objectives: To systematically review the literature regarding how permanent versus absorbable suture impacts anatomic failure in women undergoing native-tissue vaginal apical suspension. Material(s) and Method(s): MEDLINE and EMBASE were searched from their inception through 6/11/21 using pre-identified search terms. Our population included studies of women who underwent native-tissue vaginal apical suspensions (uterosacral ligament suspension (USLS) and sacrospinous ligament suspension (SSLF)). We excluded cadaver, tissue sample, or animal studies. We excluded hysteropexy and McCall culdoplasty. Our intervention was defined as permanent sutures (polytetrafluoroethylene, polypropylene, poliglecaprone 25, mersilene, silk, and nylon), excluding braided polyester suture. Our comparator group was absorbable or delayed absorbable sutures (polyglactin, polydioxanone, and polyglyconate). Outcomes included anatomic failure defined by POP-Q measurements, stage or grade, subjective symptoms of a bulge, re-operations, or re-treatments. A single composite anatomic failure proportion was determined for each study. Adverse events including suture exposure, surgery for suture complication, dyspareunia, and granulation tissue were collected. Abstracts were double-screened using Abstrackr, then full text articles were doubly screened, and then accepted articles were doubly extracted. Quality of studies was assessed using GRADE criteria. In studies using either absorbable or permanent sutures (single-arm studies), random effects meta-analyses of pooled proportions were used to assess anatomic failure. In studies investigating both suture types (comparative studies), random effect meta-analyses of pooled risk ratios were used. Analyses were performed using STATA, v.17 and p<=.05 was considered statistically significant. Result(s): 4,357 abstracts were screened, 349 full-text papers assessed, and 20 studies met eligibility criteria (Figure 1). 4 studies (all USLS) compared both suture types, and 16 were single arm (8 USLS and 8 SSLF)(6 absorbable and 10 permanent). Mean follow up was 24.3 months. The proportional anatomic failure rate of absorbable suture (n=10) was 9% (95% CI 0.06, 0.13), and permanent suture (n=14) was 15% (95% CI 0.10, 0.20) with high heterogeneity. On meta-analysis, there was no difference in relative risk of failure for permanent sutures versus absorbable sutures (n=4), RR = 0.69 (95%CI 0.20, 2.36) with substantial heterogeneity (Figure 2). Conclusion(s): Overall, failure rate was low and similar for both absorbable and permanent suture for native tissue vaginal suspension with medium term follow-up. [Formula presented] [Formula presented]Copyright © 2022

Pollack, B. L., et al. (2022). "IMPACT OF PERMANENT VERSUS ABSORBABLE SUTURE IN SACROCOLPOPEXY FOR PELVIC ORGAN PROLAPSE: A SYSTEMATIC REVIEWAND META-ANALYSIS." Female Pelvic Medicine and Reconstructive Surgery 28(6 Supplement 1): S47.
	Introduction: Sacrocolpopexies are commonly performed surgeries for apical vaginal prolapse. Either permanent or absorbable sutures are used at the discretion of the surgeon. There is limited data comparing the outcomes of permanent and absorbable sutures used during sacrocolpopexy. Our study focuses on the anatomic outcomes of permanent versus absorbable suture use on the vaginal mesh attachment in sacrocolpopexy. Objective(s): To systematically review the literature regarding how permanent versus absorbable suture impacts anatomic failure in women undergoing sacrocolpopexy. Method(s): MEDLINE and EMBASE were searched from their inception through 6/11/21 using pre-identified search terms. Our population included studies of women who underwent sacrocolpopexy. We excluded cadaver, tissue sample, or animal studies. We excluded hysteropexy. Our intervention was defined as permanent sutures (polytetrafluoroethylene, polypropylene, poliglecaprone 25, polyester, silk, and nylon). Our comparator group was absorbable or delayed absorbable sutures (polyglactin, polydiaxanone, and polyglyconate). Outcomes included anatomic failure defined using POP-Q stage or Baden Walker grade, subjective symptoms of a bulge, re-operations, or re- treatments. A single composite anatomic success proportion was determined for each study. Adverse events including suture exposure, mesh exposure, granulation tissue, surgery for suture complication, and dyspareunia were collected. Abstracts were double-screened using Abstrackr, then full text articles were doubly screened, and then accepted articles were doubly extracted. Quality of studies was assessed using GRADE criteria. In studies using either absorbable or permanent sutures (single-arm studies), random effects meta-analyses of pooled proportions were used to assess anatomic success. In studies investigating both suture types (comparative studies), random effect meta-analyses of pooled risk ratios were used. Analyses were performed using STATA, v.17 and P < =0.05 was considered statistically significant. Result(s): 4,357 abstracts were screened, 349 full-text papers assessed, and 41 studies met eligibility criteria. (Figure 1). Of these, 7 compared both suture types, and 34 used one suture type. Overall, 11 studies were RCTs, 12 were comparative (1 prospective and 11 retrospective) and 17 were single arm (8 prospective, 9 retrospective, 1 unclear direction). 4 studies had quality ratings of A, 18 were rated B, and 19 were C. Mean follow up was 17.4 months. The proportional anatomic success rate of absorbable suture (n = 13) was 90% (95% CI 0.86, 0.94), and permanent suture (n = 24) was 93% (95% CI 0.91, 0.95) with considerable heterogeneity. On meta-analysis, there was no difference in relative risk of success compared to failure for permanent sutures versus absorbable sutures (n = 7), RR = 1.01 (95% CI 0.99, 1.02) with low heterogeneity (Figure 2). Conclusion(s): Overall, failure rate was low and similar for both absorbable and permanent suture for the vaginal attachment of sacrocolpopexy with medium term follow-up.

Pollack Bracha, L., et al. (2023). "Permanent Compared With Absorbable Suture in Apical Prolapse Surgery: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 141(2): 268-283.
	Objective: To explore how permanent compared with absorbable suture affects anatomic success in native tissue vaginal suspension (uterosacral ligament suspension and sacrospinous ligament suspension) and sacrocolpopexy with mesh.; Data Sources: MEDLINE, EMBASE, and ClinicalTrials.gov were searched through March 29, 2022.; Methods of Study Selection: Our population included women undergoing apical prolapse surgery (uterosacral ligament suspension and sacrospinous ligament suspension and abdominal sacrocolpopexy). Our intervention was permanent suture for apical prolapse surgery, and our comparator was absorbable suture. We determined a single anatomic success proportion per study. Adverse events collected included suture and mesh exposure, surgery for suture and mesh complication, dyspareunia, and granulation tissue. Abstracts were doubly screened, full-text articles were doubly screened, and accepted articles were doubly extracted. Quality of studies was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. In single-arm studies using either permanent or absorbable suture, random effects meta-analyses of pooled proportions were used to assess anatomic success. In comparative studies investigating both suture types, random effects meta-analyses of pooled risk ratios were used.; Tabulation, Integration, and Results: Of 4,658 abstracts screened, 398 full-text articles were assessed and 63 studies were included (24 vaginal suspension [13 uterosacral ligament suspension and 11 sacrospinous ligament suspension] and 39 sacrocolpopexy). At 2-year follow-up, there was no difference in permanent compared with absorbable suture in uterosacral ligament suspension and sacrospinous ligament suspension (proportional anatomic success rate 88% [95% CI 0.81-0.93] vs 88% [95% CI 0.82-0.92]). Similarly, at 18-month follow-up, there was no difference in permanent compared with absorbable suture in sacrocolpopexy (proportional anatomic success rate 92% [95% CI 0.88-0.95] vs 96% [95% CI 0.92-0.99]). On meta-analysis, there was no difference in relative risk (RR) of success for permanent compared with absorbable suture for uterosacral ligament suspension and sacrospinous ligament suspension (RR 1.11, 95% CI 0.93-1.33) or sacrocolpopexy (RR 1.00, 95% CI0.98-1.03).; Conclusion: Success rates were similarly high for absorbable and permanent suture after uterosacral ligament suspension, sacrospinous ligament suspension, and sacrocolpopexy, with medium-term follow-up.; Systematic Review Registration: PROSPERO, CRD42021265848.; Competing Interests: Financial Disclosure: Cara L. Grimes reports providing Expert testimony for Johnson and Johnson. The other authors did not report any potential conflicts of interest. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Pollack, L. M., et al. (2024). "Rural/urban differences in health care utilization and costs by perinatal depression status among commercial enrollees." The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association 40(1): 26-63.
	PURPOSE: To understand differences in health care utilization and medical expenditures by perinatal depression (PND) status during pregnancy and 1-year postpartum overall and by rural/urban status. METHODS: We estimated differences in health care utilization and medical expenditures by PND status for individuals with an inpatient live-birth delivery in 2017, continuously enrolled in commercial insurance from 3 months before pregnancy through 1-year postpartum (study period), using MarketScan Commercial Claims data. Multivariable regression was used to examine differences by rurality. FINDINGS: Ten percent of commercially insured individuals had claims with PND. A smaller proportion of rural (8.7%) versus urban residents (10.0%) had a depression diagnosis (p < 0.0001). Of those with PND, a smaller proportion of rural (5.5%) versus urban residents (9.6%) had a depression claim 3 months before pregnancy (p < 0.0001). Compared with urban residents, rural residents had greater differences by PND status in total inpatient days (rural: 0.7, 95% confidence interval [CI]: 0.6-0.9 vs. urban: 0.5, 95% CI: 0.5-0.6) and emergency department (ED) visits (rural: 0.7, 95% CI: 0.6-0.9 vs. urban: 0.5, 95% CI: 0.4-0.5), but a smaller difference by PND status in the number of outpatient visits (rural: 9.2, 95% CI: 8.2-10.2 vs. urban: 13.1, 95% CI: 12.7-13.5). Differences in expenditures for inpatient services by PND status differed by rural/urban status (rural: $2654; 95% CI: $1823-$3485 vs. urban: $1786; 95% CI: $1445-$2127). CONCLUSIONS: Commercially insured rural residents had more utilization for inpatient and ED services and less utilization for outpatient services. Rural locations can present barriers to evidence-based care to address PND.

Pollack, L. M., et al. (2022). "Healthcare Utilization and Costs Associated With Perinatal Depression Among Medicaid Enrollees." American Journal of Preventive Medicine 62(6): e333-e341.
	Introduction: Differences in healthcare utilization and medical expenditures associated with perinatal depression are estimated. Method(s): Using the MarketScan Multi-State Medicaid Database, the analytic cohort included individuals aged 15-44 years who had an inpatient live birth delivery hospitalization between January 1, 2017 and December 31, 2018. Multivariable negative binomial regression models were used to estimate the differences in utilization associated with perinatal depression, and multivariable generalized linear models were used to estimate the differences in expenditures associated with perinatal depression. Analyses were conducted in 2021. Result(s): The cohort included 330,593 individuals. Nearly 17% had perinatal depression. Compared with individuals without perinatal depression individuals with perinatal depression had a larger number of inpatient admissions (0.19, 95% CI=0.18, 0.20), total inpatient days (0.95, 95% CI=0.92, 0.97), outpatient visits (14.02, 95% CI=13.81, 14.22), emergency department visits (1.70, 95% CI=1.66, 1.74), and weeks of drug therapy covered by a prescription (28.70, 95% CI=28.12, 29.28) and larger total expenditures ($5,078, 95% CI=$4,816, $5,340). Non-Hispanic Black individuals had larger differences in utilization and expenditures for inpatient services and outpatient visits but smaller differences in utilization for pharmaceutical services associated with perinatal depression than non-Hispanic White individuals. Hispanic individuals had larger differences in utilization for outpatient visits but smaller differences in utilization for pharmaceutical services associated with perinatal depression than non-Hispanic White individuals. Conclusion(s): Individuals with perinatal depression had more healthcare utilization and medical expenditures than individuals without perinatal depression, and differences varied by race/ethnicity. The findings highlight the need to ensure comprehensive and equitable mental health care to address perinatal depression.Copyright © 2022

Polonio, A. M., et al. (2023). "Differential Effects of Tobacco on Telomeres and Fertility Depending on Women's Age and Ovarian Reserve." Reproductive Sciences 30(Supplement 1): 181A-182A.
	Introduction: Literature have highlighted the harmful effects of cigarette smoking on fertility, worsening the results of ovarian stimulations (OS). Indeed, tobacco's toxins can interfere with the metabolism of steroid hormones, which are critical for follicula growth. Furthermore, tobacco exposure accelerates cell aging, as shown in blood cells from smokers which have shorter telomeres. Thus, the objective of the study was to evaluate the impact of cigarette smoking on telomeres and fertility outcomes of women with different fertility profiles. Method(s): We conducted a prospective cohort study in IVIRMA Madrid with three groups of women: oocyte donor, normal ovarian reserve (NOR; AMH>=2ng/ml) and diminished ovarian reserve (DOR; AMH<2ng/ml). Women were enrolled between September and December 2021. Smoking status was based on the patient's reports and classifIed as nonsmokers or active smokers. Blood telomere length (TL) was analyzed by quantitative fuorescent in situ hybridization. Fertility parameters were assessed according to IVIRMA standard protocols. Result(s): A total of 26 oocyte donors (14 smokers, 25.2+/-3.9 years; 12 nonsmokers, 24.5+/-3.6 years), 18 DOR patients (9 smokers, 38.1+/-3.6 years; 9 nonsmokers, 38.0+/-3.0 years) and 15 NOR patients (7 smokers, 35.8+/-2.2 years; 6 nonsmokers, 36.5+/-2.0 years) were recruited. The years of tobacco exposure for donors were 9.0+/-3.2, for DOR group 19.6+/-6.2 and, for NOR group 18.2+/-5.9. Mean TL was statistically signifcant lower in smokers compared to non-smokers of DOR and NOR groups (79.7+/-0.2 vs 83.7+/-0.3 a.u (DOR), p = <0.0001; 73.7+/-0.8 vs 76.3+/-0.4 a.u (NOR); p = <0.0001). In donors, TL was similar in smokers and nonsmokers. Serum estradiol levels at trigger day were lower in smokers in the three groups, but only statically signifcant in DOR group (989+/-134.8 vs 1737+/-917.7 pcg/ml; p=0.03). Finally in DOR group, the number of follicles were statistically signifcantly lower in smokers compared to non-smokers (4.6+/-0.6 vs 8.7+/-1.3, p=0.01), whereas in NOR and donor groups, means were similar. As for the number of oocytes retrieved, the means were higher in nonsmokers but not statically signifcant in any group (4.4+/-0.7 vs 5.7+/-1.8 (DOR); 9.8+/-1.4 vs 16.1+/-4.8 (NOR); 13.07+/-12.0 vs 19.9+/-2.8 (Donors)). Conclusion(s): Results suggest that smoking afected the TL of DOR and NOR women, who had a longer time of tobacco exposure. Together with TL shortening, only smoking DOR women had lower estradiol levels and oocyte means, suggesting an additive effect of tobacco with compromised ovarian reserve. Thus, more awareness campaigns should be done directed to women who want to have children.

Polterauer, S., et al. (2022). "Topical imiquimod compared with conization to treat cervical high-grade squamous intraepithelial lesions: Multicenter, randomized controlled trial." Gynecologic Oncology 165(1): 23-29.
	Objective: In a previous phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious treatment for high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to investigate the non-inferiority of a 16-week topical, self-applied IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with HSIL.; Methods: Phase III randomized, controlled, multicenter, open trial performed by Austrian Gynecologic Oncology group. Patients with histologically proven cervical intraepithelial neoplasia (CIN)2 (30 years and older) or CIN3 (18 years and older) and satisfactory colposcopy were randomized to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test result 6 months after start of the treatment. Secondary endpoints were histological outcome and HPV clearance rates.; Results: Within 3 years 93 patients were randomized, received the allocated treatment and were available for ITT analysis. In the IMQ group negative HPV test at 6 months after treatment start was observed in 22/51 (43.1%) of patients compared to 27/42 (64.3%) in the LLETZ group on ITT analysis (rate difference 21.2%-points, 95% two-sided CI: 0.8 to 39.1). In the IMQ group histologic regression 6 months after treatment was observed in 32/51 (63%) of patients and complete histologic remission was observed in 19/51 (37%) of patients. Complete surgical resection was observed in 84% after LLETZ.; Conclusion: In women with HSIL, IMQ treatment results in lower HPV clearance rates when compared to LLETZ. LLETZ remains the standard for women with HSIL when treatment is required.; Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01283763, EudraCT number: 2012-004518-32.; Competing Interests: Declaration of Competing Interest None. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Pomel, C., et al. (2021). "Laparoscopic management of advanced epithelial ovarian cancer after neoadjuvant chemotherapy: a phase II prospective multicenter non-randomized trial (the CILOVE study)." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 31(12): 1572-1578.
	OBJECTIVE: The aim of this study was to explore the feasibility and safety of the laparoscopic approach after neoadjuvant chemotherapy among selected chemosensitive patients with advanced ovarian cancer. METHOD(S): The CILOVE study was a phase II prospective non-randomized multicenter study. It aimed to enroll 47women with unresectable disease at the time of initial diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage IV and/or diffuse extensive carcinomatosis for advanced FIGO stage IIIC or patients unfit to withstand radical primary surgery), in response to chemotherapy and fit to undergo laparoscopy. RESULT(S): Among the 48 patients enrolled in the trial, 44 (92%) patients underwent exploratory staging laparoscopy and, as a result, 41 patients were eligible for cytoreductive surgery. Among them, 32 were intended to be managed by laparoscopy and nine patients were managed by laparotomy. The conversion rate to laparotomy was 9.4% (3/32) and the reasons were multiple surgical adhesions (n=1), miliary carcinomatosis and adhesion to the intraperitoneal mesh (n=1), and poor laparoscopic evaluation of transverse colon involvement (n=1). All except one patient had optimal cytoreduction (97% complete cytoreduction, 3% incomplete cytoreduction (residual tumor <2.5mm)). The median operative time was 267min (range 146-415) and the median estimated blood loss was 150mL (range 0-500). Two patients had intra-operative complications: one diaphragm rupture that was repaired during laparoscopy and one bradycardia. Six patients experienced early post-operative complications (<1month), but there were no grade 3 and 4 complications (3 infections, 1 lymphoedema, 2 hemorrhage). After cytoreductive laparoscopy, the percentage of patients without progression at 12 months was 87.5%. CONCLUSION(S): Interval ovarian cytoreduction by a laparoscopic approach is safe and feasible for patients with a favorable response to chemotherapy. With the widespread use of neoadjuvant chemotherapy in the management of advanced ovarian cancer, a minimally invasive approach may be a potential option.Copyright © IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Pomeranz, M., et al. (2021). "A novel method for office aspiration curettage in cases of retained products of conception: A randomized controlled trial." Acta Obstetricia et Gynecologica Scandinavica 100(11): 2076-2081.
	INTRODUCTION: Missed abortion can be treated with medication or aspiration curettage. A Karman aspiration cannula is another option. We evaluated its success in evacuating retained products of conception (RPOC) based on symptoms, endometrial thickness, endometrial irregularity, and blood flow seen on Doppler ultrasound (indicative of placenta). MATERIAL AND METHODS: This prospective, randomized, nonblinded trial was conducted in a university-affiliated medical center. It included 40 women diagnosed with missed abortion and two failed courses of 600 µg buccal misoprostol, one week apart, randomly assigned to treatment or controls. One week after the second misoprostol course, immediately after evaluating endometrial thickness, endometrial irregularity using Doppler ultrasound, and with blood flow indicative of RPOC, women in the aspiration group underwent endometrial suction with a Karman aspiration cannula. The 5-6 mm cannula attached to a 60 mL syringe was inserted into the uterus under ultrasound guidance. The contents were aspirated until the uterus was empty. Control group patients did not receive additional treatment. All were scheduled for ambulatory, operative hysteroscopy under anesthesia 1 month later (departmental protocol). On that day, all women with RPOC on Doppler ultrasound underwent hysteroscopy. Bleeding days, days with pain, pain according to visual analog scale, length of hospitalization, and infection rate were recorded. NIH clinical trial registration number NCT02917785. RESULTS: In the study group, 90% did not need hysteroscopy, compared with 50% of controls (p = 0.014). No complications were noted. At all visits, we used Doppler ultrasound to exclude or confirm RPOC. Pathology revealed RPOC in all women who underwent aspiration. Average visual analog scale score for office aspiration (n = 20) was 4.9 ± 3.6. vs. 6.3 ± 3.4 for the first (p = 0.157) and 4.7 ± 3.3 for the second (p = 0.836) misoprostol treatment cycle. The treatment group experienced 6.1 days of bleeding and the control group experienced 1.4 days (p = .006). CONCLUSIONS: Based on our criteria of diagnosing RPOC according to symptoms, endometrial thickness, endometrial irregularity, and blood flow indicative of placental tissue seen on Doppler ultrasound and histo-pathological confirmation, aspiration using Karman cannula can be an effective therapeutic approach. It may be a safe alternative for women with RPOC after misoprostol failure.

Pongsatha, S. and T. Tongsong (2021). "Intravaginal misoprostol versus sublingual misoprostol for second trimester pregnancy termination: a randomized controlled trial." Clinical and experimental obstetrics & gynecology 48(1): 122‐127.
	Objective: To compare the efficacy and adverse effects of 400 mcg misoprostol for second trimester pregnancy termination via the intravaginal or sublingual route. Methods: In this study, 170 women at GA 14‐28 weeks underwent termination of pregnancy. They were randomized to receive either intravaginal or sublingual 400 mcg misoprostol at 6 hour intervals until fetal expulsion occurred or within 48 hours after the initiation of the first dose of misoprostol. The primary outcomes were median abortion time and percentage of failure. The secondary outcomes included rates of maternal adverse effects, oxytocin use and analgesia requirement. Results: Intravaginal misoprostol demonstrates significantly greater efficacy for pregnancy termination compared to sublingual misoprostol at the same dosage. The median time to abortion was 16.66 hours and 22.88 hours in the intravaginal group and sublingual group respectively. Maternal adverse effects, specifically rate of chill and diarrhea, were statistically higher in the sublingual group. Conclusion: Intravaginal misoprostol was superior to sublingual misoprostol in terms of shorter abortion time and fewer adverse effects. In addition the rate of oxytocin use was found to be higher in the sublingual group. In conclusion misoprostol via the intravaginal route should be considered for second trimester pregnancy termination rather than the sublingual route due to greater efficacy and fewer adverse maternal effects.

Poniewierza, P. and G. Panek (2022). "Cervical Cancer Prophylaxis-State-of-the-Art and Perspectives." Healthcare (Basel, Switzerland) 10(7).
	Background: Each year 604,127 new cases of cervical cancer (CC) are diagnosed, and 341,831 individuals die from the disease. It is the fourth most common cancer among women and the fourth most common cause of death from female cancers worldwide. The pathogenesis of CC is associated with human papillomavirus (HPV) infections and consists of several steps involving cell proliferation outside the human body's control mechanisms. Strategies to prevent CC are based on screening and vaccination.; Scope of the Review: The aim of this paper was to collect and analyze the available literature on the issue of CC prevention and the impact of the COVID-19 pandemic on its implementation. For this purpose, PubMed and Google Scholar databases were searched using keywords, such as "cervical cancer"; "HPV"; "prevention"; "prophylaxis"; "vaccination"; "screening" and "COVID-19" in different variations. Only articles published since 2018 were included in the study.; Conclusions: Selected European countries have different CC prevention programs funded by national budgets. This translates into observed differences in the risk of death from CC (age-standardized rate Malta = 1.1, Poland = 5.9). COVID-19 pandemic due to disruption of CC screening may exacerbate these differences in the future. To improve the situation, new screening methods, such as p16/Ki67, HPV self-testing, and the use of artificial intelligence in colposcopic assessment, should be disseminated, as well as free HPV vaccination programs implemented in all countries. The search for new solutions is not without significance and entails ultra-sensitive screening tests for risk groups (mRNA E6/E7, SOX1/SOX14), HPV vaccines with shorter dosing schedules, and new therapeutic pathways using nanotheranostics.

Pontoriero, A., et al. (2023). "Recurrent Gynecological Tumors in Previously Irradiated Patients. Does Re-Irradiation with Stereotactic Body Radiotherapy Have a Role? A Systematic Review." Clinical and Experimental Obstetrics and Gynecology 50(6): 134.
	Background: Re-irradiation of patients with previously irradiated gynecological tumors represents one of the hot topics of modern oncology. It is generally performed using Brachytherapy (alone or after external beam radiation therapy (EBRT) re-treatment) or Stereotactic Body Radiotherapy (SBRT). Literature provides few data concerning SBRT re-irradiation (re-RT). Here we provided a statistical and comparative analysis of the studies to make a general assessment of the efficacy and reliability of SBRT, considering the potential benefits achievable in terms of local control, overall survival and toxicity. Method(s): A computerized literature search was performed in 3 electronic databases (MEDLINE, EMBASE, and Cochrane) from 1996 to 2020. Only studies analysing outcomes of re-irradiated (re-I) patients were taken into consideration. Quality assessment score and risk of bias were assessed for each article. Random-effects models were used due to great subjectivity given the lack of related control groups in the non-comparative studies and a tendency towards high heterogeneity (examined by the Cochran Q chi-square test and the I2 statistic). To determine the pooled 2-year Overall Survival (OS) and 2-year Local Control (LC) and >=Grade 3 (G3) treatment-related toxicities, an established meta-analysis technique over single and multi-arm studies was performed. Result(s): Of 21 articles focusing on the role of SBRT in recurrent gynaecological cancers, were identified. Only 7 articles, published between 2009 and 2020, with outcomes limited to re-I patients and specific radiotherapy techniques were included. The selected studies counted a total of 196 patients, 157 of whom were previously irradiated. With a median follow up time of 14.5 months, using SBRT re-I technique, the pooled 2-year OS of 52.7% (95% confidence interval (CI): 0.372 to 0.651) and 2-year LC of 75.7% (95% CI: 0.614 to 0.852) were observed. SBRT re-irradiation technique does not affect toxicities with pooled >=G3 late toxicities being 8.7% (95% CI: -0.0944 to 0.267). Conclusion(s): According to our review, SBRT re-irradiation technique seems to be feasible and safe, when brachytherapy re-RT technique is not available. Further studies are warranted to standardize the best radiation therapy in recurrent gynaecological cancer.Copyright © 2023 The Author(s). Published by IMR Press.

Pontrelli, G., et al. (2022). "End-to-end versus side-to-end anastomosis after bowel resection for deep infiltrating endometriosis: A retrospective study." Journal of Gynecology Obstetrics and Human Reproduction 51(10): 102472.
	Objective: Deep infiltrating endometriosis(DIE) of the bowel may require segmental bowel resection. The subsequent reconstruction can be performed through an end-to-end(E-E) or a side-to-end (S-E)anastomosis, the latter being used in low resection due to the reduced risk of anastomotic leakage. This study aims at comparing those two anastomosis techniques in women submitted to bowel resection for DIE, in terms of post-operative morbidity and functional outcomes.; Methods: This was a single-center retrospective study on women undergoing laparoscopic rectal resection for deep infiltrating endometriosis with subsequent E-E or S-E anastomosis performed according to the level of rectal resection. The two groups were compared for postoperative complication rates and functional outcomes by means of validated questionnaires.; Results: The study population included 30 patients undergoing a S-E anastomosis (group A), and 49 cases undergoing an E-E anastomosis (group B). No differences were found between the two groups in terms of length of hospital stay, anastomotic leakages, protective ileostomies and short-term complications. At follow up no differences were found between the two groups in terms of bowel function and pain symptoms.; Conclusions: A S-E anastomosis in case of low rectal resections for DIE presents similar complication rates and functional outcomes compared with an E-E anastomosis.; Competing Interests: Declaration of Competing Interest all Authors declare that there is no conflict of interests regarding the publication of this article (Copyright © 2022. Published by Elsevier Masson SAS.)

Poordast, T., et al. (2022). "Comparing the quality of life of endometriotic patients' before and after treatment with normal and infertile patients based on the EHP30 questionnaire." BMC Women's Health 22(1): 553.
	Objective: This study aimed to determine the quality of life (QOL), in patients with endometriosis ± infertility (B and C groups) and compare those to healthy women, and also infertile groups without endometriosis as a control groups (A and D), considering the fact that endometriosis and infertility reduces the quality of life in patients.; Methods: The present prospective comparative study was carried out between January 2018 and September 2020. A total of 400 women were included (100 women in each group). The participants filled in a validated questionnaire of quality of life, Endometriosis Health Profile-30 (EHP-30), and a visual analog scale of pain used, at the first visit, and 3 months after the medical or surgical treatment in the endometriosis group without infertility, additionally.; Results: The majority of the patients were married, categorized in the middle-class of socio-economic state and housewives. They were of Persian descent. BMI was high in the infertile groups; however, the time of infertility was not different between the two groups of B and C (P = 0.054). The mean score of QOL was significantly lower in B, C, and D groups in comparison to the healthy women as the control group (A) (P < 0.001). Moreover, the infertile group (B), in comparison to endometriosis ± infertility groups (C and D), had the lowest mean score of QOL (P < 0.001). In each group, those who were older and had better educational level reported a better quality of life than other participants in that group. Social support plays a very important role in reducing the endometriosis related pain symptoms both before and after treatment. Three months after the treatment of endometriosis (D), a significant improvement was observed in all the aspects of QOL-related endometriosis. Nonetheless, the improvement of the quality of life in the surgical group was significantly higher than that in the medical treatment. The mean visual analog score of pain decreased from 62.22 ± 22.78, to 5.15 ± 2.73 following the surgical treatment (P < 0.001).; Conclusion: The lowest quality of life belonged to the infertile group, followed by the endometriosis group. The quality of life of the endometriosis group improved after the treatment. Thus, endometriotic patients' treatment in terms of improvement of quality of life should be considered by all professional health care teams. (© 2022. The Author(s).)

Poordast, T., et al. (2021). "Aloe Vera; A new treatment for atrophic vaginitis, A randomized double-blinded controlled trial." Journal of Ethnopharmacology 270: 113760.
	AIM OF THE STUDY: Vaginal atrophy is of the most common problems during menopause with significant psychosocial and medical consequences. Estrogen as an approved therapy for vaginal atrophy can be associated with adverse effects and several contraindications in menopause patients. The aim is to compare the effect of Aloe Vera vaginal cream with commercially available estrogen vaginal cream for management of vaginal atrophy in menopause females. MATERIALS AND METHODS: This is a double-blinded randomized controlled trial on 60menopause female with complaints of vaginal atrophy symptoms. Subjects were randomly allocated in two groups of 30 patients, named as estrogen and Aloe Vera groups. Vaginal health index (VHI), maturity value (MV), vaginal cytologic smear, transvaginal sonography (TVS) and severity of symptoms related to vaginal atrophy were assessed before and after 6-weeks of vaginal cream administration. RESULTS: Comparison of MV before and after treatment revealed that superficial cells were significantly increased after administration of both vaginal cream (6.67 VS 54.33 in Aloe Vera group; 4.33 VS 59.67 in estrogen group). In addition, VHI (13.83 vs 20.13 in Aloe Vera group; 13.97 vs 19.93 in estrogen group) and symptoms of vaginal atrophy (3.63 vs 1.10 in Aloe Vera group; 3.90 vs 0.66 in estrogen groups) were also significantly improved after treatment in both groups. There was no significant difference between groups after treatment except for fluid volume with a superiority in Aloe Vera group (P-value = 0.004) CONCLUSION: Aloe Vera vaginal cream can be as effective as estrogen vaginal cream in the management of vaginal atrophy in menopause females.

Popiel, P., et al. (2022). "Voided Volume for Assessment of Bladder Emptying After Female Pelvic Floor Surgery: A Randomized Controlled Trial." Urogynecology 28(12): 811-818.
	Importance: To study alternative voiding trial (VT) methods after urogynecologic surgery that may potentially decrease catheterization. Objective(s): The aim of the study is to compare voiding assessment based on a minimum spontaneous voided volume of 150 mL with the standard retrograde fill (RF) approach in women after urogynecologic procedures. Study Design: Women undergoing urogynecologic surgery were randomized to RF or spontaneous void (SV) groups. Women in the RF group had their bladders backfilled with 300 mL of saline before catheter removal, those in the SV group did not. To pass the VT, patients in the RF group were required to void 150 mL at one time within 60 minutes, and patients in the SV group had to do the same within 6 hours. The primary outcome was the VT failure rate. We also compared the false pass rate, urinary tract infections, satisfaction, and preference of VT method. Result(s): One hundred nine women were enrolled in the study, 54 had SV and 55 underwent RF. Baseline characteristics were not significantly different other than history of prior hysterectomy. There was no significant difference in procedures between the groups. There was no difference in VT failure rate between the groups - SV (7.4%) and RF (12.7%, P = 0.39). The false pass rate was 0 in each group. Urinary tract infection rates were similar between SV (14.8%) and RF (14.5%) groups (P = 0.34). Patient satisfaction for VT method was not significantly different. Conclusion(s): Spontaneous VT was not superior to retrograde void trial. Therefore, we cannot recommend one method of VT after urogynecologic surgery. Condensation Voiding assessment based on minimum SV of 150 mL is comparable with VT with RF after surgeries for prolapse and urinary incontinence.Copyright © 2022 American Urogynecologic Society.

Popiel, P., et al. (2023). "ASSESSMENT OF PATIENT SATISFACTION WITH HOME VERSUS OFFICE INDWELLING CATHETER REMOVAL PLACED FOR URINARY RETENTION AFTER FEMALE PELVIC FLOOR SURGERY: A RANDOMIZED CONTROLLED TRIAL." American Journal of Obstetrics and Gynecology 229(3): 312.e311-312.e318.
	OBJECTIVES: To assess patient satisfaction with location of indwelling catheter removal placed for urinary retention after urogynecologic surgery. MATERIALS AND METHODS: All adult women who were diagnosed with urinary retention requiring post-operative indwelling catheter insertion after undergoing surgery for urinary incontinence and/or pelvic organ prolapse were eligible for this randomized controlled study. They were randomly assigned to catheter removal at home or in the office. Those who were randomized to home removal were taught how to remove the catheter prior to discharge, and discharged home with written instructions, a voiding hat, and 10 mL syringe. All patients had their catheter removed 2-4 days after discharge. Those patients who were allocated to home removal were contacted in the afternoon by the office nurse. Subjects who graded their force of urine stream 5, on a scale of 0-10, were considered to have safely passed their voiding trial. For patients randomized to the office removal group, the voiding trial consisted of retrograde filling the bladder to maximum they could tolerate up to 300 mL. Urinating >50% of instilled volume was considered successful. Those who were unsuccessful in either group had catheter reinsertion or self-catheterization training in the office. Primary study outcome was patient satisfaction, measured based on patients' response to a question "How satisfied were you with the overall removal process of the catheter?". A visual analogue scale was created to assess patient satisfaction and 4 secondary outcomes. A sample size of 40 participants per group were needed to detect a 10 mm difference in satisfaction between groups on the visual analogue scale. This calculation provided 80% power and an alpha of 0.05. Final number accounted for 10% loss to follow up. We compared the baseline characteristics including urodynamic parameters, relevant perioperative indices, and patient satisfaction between the groups. RESULTS: Of the 78 women enrolled in the study, 38 (48.7%) removed their catheter at home and 40 (51.3%) had an office visit for catheter removal. Median and interquartile range (IQR) for age, vaginal parity, and body mass index (BMI) were 60 (49-72) years, 2 (2-3), and 28 (24-32) kg/m2, respectively, in the overall sample. Groups did not differ significantly in age, vaginal parity, body mass index, prior surgical history, or type of concomitant procedures. Patient satisfaction was comparable between the groups, with a median score (IQR) of 95 (87-100) in the home catheter removal group and 95 (80-98) in the office catheter removal group (p=0.52). Voiding trial pass rate was similar between women who underwent home (83.8%) versus office (72.5%) catheter removal (p=0.23). No participants in either group had to emergently come into the office or hospital due to inadequate voiding afterwards. Within 30 days post operatively, a lower proportion of women in the home catheter removal group (8.3%) had urinary tract infection, compared to patients in the office catheter removal group (26.3%) (p=0.04). CONCLUSION: In women with urinary retention after urogynecologic surgery, there is no difference in satisfaction with regards to location of indwelling catheter removal when comparing home and office.

Popoutchi, P., et al. (2021). "SURGICAL TECHNIQUES FOR THE TREATMENT OF RECTAL ENDOMETRIOSIS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS AND OBSERVATIONAL STUDIES." Arquivos de gastroenterologia 58(4): 548-559.
	Background: Endometriosis is a common disease in reproductive-age women and it is estimated to occur in up to 50% of those with infertility. Intestinal involvement is reported in up to a third of the cases. This condition is related to chronic pain and loss of quality of life, resulting in emotional, social and economic costs. Treatment consists of hormonal block and surgical resection, with variable side effects and efficacy. The best choice for surgical treatment for rectal endometriosis is a matter of discussion regarding the indication and the best technique to be employed.; Objective: To summarize data on indications, results and complications of surgical techniques for the treatment of rectal endometriosis.; Methods: This comprehensive systematic review is a compilation of the available literature and discussion, carried out by a team with experience in the surgical treatment of intestinal endometriosis. Data regarding indications, results and complications of conservative and radical techniques for the surgical treatment of rectal endometriosis was carefully reviewed. Searches of PubMed, EMBASE, and CENTRAL up to May 2021 were performed to identify randomized controlled trials (RCTs) and observational studies that compared at least two of the three surgical techniques of interest (i.e., shaving, discoid resection, segmental resection).; Results: One RCT and nine case series studies with a total of 3,327 patients met the eligibility criteria. Participants ages ranged from a mean of 30.0 to 37.9 years old. Mean follow-up ranged from 1.2 to 42.76 months. With regards the methodological quality, overall the included studies presented a low risk of bias in the majority of the domains. Surgical treatment of rectal endometriosis is indicated for patients with obstructive symptoms and those with pain scores above 7/10. Patients with disease involving beyond muscularis propria of the rectum, documented in magnetic resonance imaging or transvaginal pelvic ultrasound with intestinal preparation, are candidates for discoid or segmental resection. The presence of multifocal disease, extension greater than 3 cm and infiltration greater than 50% of the loop circumference favor the radical technique. The distance from the lesion to the anal verge, age, symptoms and reproductive desire are other factors that influence the choice of the technique to be employed. The risk of complications and unfavorable functional results seems to be directly related to the complexity of the procedure.; Conclusion: The choice of surgical technique performed for the treatment of rectal endometriosis is a matter of discussion and depends not only on the preoperative staging, but also on the patient's expectations, risks and potential complications, recurrence rates and the expertise of the multidisciplinary team.

Porcari, I., et al. (2024). "Clinician perspectives on hysterectomy versus uterine preservation in pelvic organ prolapse surgery: A systematic review and meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.
	BACKGROUND: Previous reviews on hysterectomy versus uterine-sparing surgery in pelvic organ prolapse (POP) repair did not consider that the open abdominal approach or transvaginal mesh use have been largely abandoned. OBJECTIVES: To provide up-to-date evidence by examining only studies investigating techniques currently in use for POP repair. SEARCH STRATEGY: MEDLINE and Embase databases were searched from inception to January 2023. SELECTION CRITERIA: We included randomized and non-randomized studies comparing surgical procedures for POP with or without concomitant hysterectomy. Studies describing open abdominal approaches or transvaginal mesh implantation were excluded. DATA COLLECTION AND ANALYSIS: A random effect meta-analysis was conducted on extracted data reporting pooled mean differences and odds ratios (OR) between groups with 95% confidence intervals (CI). MAIN RESULTS: Thirty-eight studies were included. Hysterectomy and uterine-sparing procedures did not differ in reoperation rate (OR 0.93; 95% CI 0.74-1.17), intraoperative major (OR 1.34; 95% CI 0.79-2.26) and minor (OR 1.38; 95% CI 0.79-2.4) complications, postoperative major (OR 1.42; 95% CI 0.85-2.37) and minor (OR 1.18; 95% CI 0.9-1.53) complications, and objective (OR 1.38; 95% CI 0.92-2.07) or subjective (OR 1.23; 95% CI 0.8-1.88) success. Uterine preservation was associated with a shorter operative time (-22.7 min; 95% CI -16.92 to -28.51 min), shorter hospital stay (-0.35 days, 95% CI -0.04 to -0.65 days), and less blood loss (-61.7 mL; 95% CI -31.3 to -92.1 mL). When only studies using a laparoscopic approach for both arms were considered, no differences were observed in investigated outcomes between the two groups. CONCLUSIONS: No major differences were observed in POP outcomes between procedures with and without concomitant hysterectomy. The decision to preserve or remove the uterus should be tailored on individual factors.

Porchia Leonardo, M., et al. (2020). "Diets with lower carbohydrate concentrations improve insulin sensitivity in women with polycystic ovary syndrome: A meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 248: 110-117.
	Objective: Women with polycystic ovary syndrome (PCOS) are associated with increased levels of insulin resistance (IR). Other than treatment with insulin-sensitizing drugs, specialized diets have also been implemented to reduce the patient's IR. However, the capacity of certain diets, concerning with the severity of the patient's IR, to improve insulin sensitivity has not fully been explored. Therefore, we conducted a meta-analysis to determine in PCOS subjects from low to severe IR, if hypocaloric diets improve insulin sensitivity.; Study Design: PubMed, SCOPUS, EBSCO, and LILACS databases and retrieved studies' bibliographies were searched for prospective studies that investigated the association between diets and IR in PCOS women until October 2018. Diet was defined as a modification of the patients' nutrition intake according to caloric restriction, change in protein intake, or by using a specialized diet. IR measures (HOMA1-IR), pre- and post-intervention were extracted. Using Comprehensive Meta-Analysis software, depending on the level heterogeneity, determined by the ψ 2 -based Q-test and the I 2 -test, fixed-effects or random-effects models were used to calculate the pooled standard paired differences (SPD) and 95 %CI.; Results: 20 publications (25 studies) fulfilled the inclusion criteria. Due to the heterogeneity of the diets, the random-effects model was used. In 48 % of the studies, the diets led to a decrease of IR, where 44 % had no effect. In 2 studies, the diets increased IR. Overall, the diets decreased IR (SPD=-0.58; 95 %CI: -0.81 to -0.36). Subjects with severe IR (HOMA1-IR>4.2) had a marked improvement (SPD=-1.22; 95 %CI: -1.61 to -0.84). Moreover, diets low in carbohydrate (<50 %) was also determined to improve IR (SPD=-0.86; 95 %CI: -1.23 to -0.50).; Conclusions: Here, we demonstrate that diets are more likely to improve IR in PCOS women with severe IR. Therefore, it is crucial to determine a subject's IR status before considering any intervention containing a diet.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Porta-Roda, O., et al. (2023). "Vaginal packing after vaginal hysterectomy: systematic review and recommendations." International Urogynecology Journal 34(4): 789-796.
	Introduction and hypothesis: Vaginal packing is often used after vaginal hysterectomy to reduce the risk of haemorrhagic and infectious complications, but the procedure may impair spontaneous bladder emptying and necessitate permanent bladder catheterization, which itself increases the risk of urinary infection, patient bother, delayed discharge, and increased costs. This systematic review was aimed at assessing the complications and outcomes associated with vaginal packing after vaginal hysterectomy. Method(s): We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, using the Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework to define eligibility. Following data synthesis and subgroup analyses, we assessed the certainty of evidence according to GRADE guidance and formulated a clinical recommendation. Result(s): The review included four clinical trials (involving 337 participants). These provided no clear evidence that vaginal packing led to clinically meaningful reductions in adverse effects, such as vaginal bleeding, hematoma formation, or postoperative vaginal cuff infection. Overall, the intervention produced no clear benefit regarding the predefined outcomes. Conclusion(s): Routine vaginal packing after vaginal hysterectomy had no clear benefit on outcomes. We therefore advise against this procedure.Copyright © 2022, The International Urogynecological Association.

Porter, L. S., et al. (2022). "Evaluating a couple communication skills training (CCST) intervention for advanced cancer: study protocol for a randomized controlled trial." Trials 23(1): 712.
	BACKGROUND: For patients and their intimate partners, advanced cancer poses significant challenges that can negatively impact both individuals and their relationship. Prior studies have found evidence that couple-based communication skills interventions can to be beneficial for patients and partners. However, these studies have been limited by reliance on in-person treatment delivery and have not targeted couples at high risk for poor outcomes. This study tests the efficacy of a Couples Communication Skills Training (CCST) intervention delivered via videoconference for couples reporting high levels of holding back from discussing cancer-related concerns, a variable associated with poorer psychological and relationship functioning. METHODS: This RCT is designed to evaluate the efficacy of CCST in improving patient and partner relationship functioning (primary outcome). Secondary outcomes include patient and partner psychological functioning and patient symptoms and health care use. We also examine the role of objective and self-reported communication behaviors as mediators of treatment effects. Two hundred thirty patients with advanced lung, gastrointestinal, genitourinary, and breast cancer and their partners will be randomized to CCST or an education control intervention. Participants in both conditions complete self-reported outcome measures at baseline, mid-treatment, post-treatment, and 3 months post-treatment. Objective measures of communication are derived from video-recorded couple conversations collected at baseline and post-treatment. An implementation-related process evaluation (assessing implementation outcomes and potential barriers to/facilitators of implementation) will be conducted to inform future efforts to implement CCST in real-world settings. DISCUSSION: This trial can yield important new knowledge about effective ways to improve patient and partner adjustment to advanced cancer. TRIAL REGISTRATION: This study trial is registered at clinicaltrials.gov (Trial # NCT04590885); registration date: October 19, 2020.

Post, C. C. B., et al. (2021). "Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial." International Journal of Radiation Oncology, Biology, Physics 109(4): 975-986.
	PURPOSE: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). METHODS AND MATERIALS: In the study, 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiation therapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiation therapy alone. Toxicity was graded using Common Terminology Criteria for Adverse Events, version 3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28 subscales and compared with normative data. An as-treated analysis was performed. RESULTS: Median follow-up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiation therapy versus 46 (24%) who had received radiation therapy alone (P = .008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, P = .18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiation therapy in 6% (vs 0% after radiation therapy, P < .001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, P < .001 at 3 years; 24% vs 9%, P = .002 at 5 years). Up to 3 years, more patients who had chemoradiation therapy reported limb weakness (21% vs 5%, P < .001) and lower physical (79 vs 87, P < .001) and role functioning (78 vs 88, P < .001) scores. Both treatment groups reported similar long-term global health/quality of life scores, which were better than those of the normative population. CONCLUSIONS: This study shows a long-lasting, clinically relevant, negative impact of chemoradiation therapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer.

Post, C. C. B., et al. (2022). "Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial)." Gynecologic Oncology 165(2): 223-229.
	Background: Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer.; Patients and Methods: Patients with metastatic or recurrent endometrial cancer were enrolled. Patients received durvalumab 1500 mg intravenously q4w and olaparib 300 mg 2dd until disease progression, unacceptable toxicity, or patient withdrawal. Patients with at least 4 weeks of treatment were evaluable for analysis. The primary endpoint was progression-free survival at 6 months. Evidence for efficacy was defined as progression-free survival at 6 months in ≥50% of patients. Secondary endpoints included safety, objective response and overall survival.; Results: From July 2019, through November 2020, 55 patients were enrolled. At data cut-off (September 2021), 4 of the 50 evaluable patients were still on treatment. Seventeen patients (34%) were progression-free at 6 months. Objective response rate was 16% (95% CI, 8.3 to 28.5) with 1 complete and 7 partial responses. With a median follow-up of 17.6 months, median progression-free survival was 3.4 months (95% CI, 2.8 to 6.2) and median overall survival was 8.0 months (95% CI, 7.5 to 14.3). Grade 3 treatment-related adverse events occurred in 8 patients (16%), predominantly anemia. There were no grade 4 or 5 treatment-related adverse events.; Conclusion: The combination of durvalumab and olaparib was well tolerated, but did not meet the prespecified 50% 6-month progression-free survival in this heterogeneous patient population with advanced endometrial cancer.; Competing Interests: Declaration of Competing Interest Study drugs and an unrestricted grant were supplied by AstraZeneca. Outside this work: JRK has received study grants from AstraZeneca and Novartis and is a steering committee member for AstraZeneca, GSK, Novartis and Pfizer. GSS reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen. CLC has received research support to institution from Varian, Elekta, and compensation to institution for time spent on IDMC membership from Merck and on invited presentations from GSK. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Pothuri, B., et al. (2024). "Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial." Gynecologic Oncology 184: 168-177.
	Objective: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. Method(s): PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (+/-7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (+/-7 days) thereafter while the patient received study treatment. Result(s): Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. Conclusion(s): Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.Copyright © 2024 The Authors

Poulsen, L. C., et al. (2022). "Effects of letrozole cotreatment on endocrinology and follicle development in women undergoing ovarian stimulation in an antagonist protocol." Human Reproduction 37(7): 1557-1571.
	STUDY QUESTION: What are the downstream endocrine and paracrine consequences of letrozole (LZ) cotreatment during ovarian stimulation and is follicle growth and recruitment affected? SUMMARY ANSWER: Letrozole cotreatment induces marked changes in both the follicular and luteal phase endocrinology causing potentiation of follicle diameter and an improved corpus luteum function without affecting the secondarily recruited follicle cohort. WHAT IS KNOWN ALREADY: Letrozole is a third-generation aromatase inhibitor that is well-established as an effective ovulatory agent, while its possible benefits in standard in vitro fertilization protocols are less thoroughly investigated. STUDY DESIGN, SIZE, DURATION: This study included a double-blinded, placebo-controlled, randomized study with LZ or placebo intervention during ovarian stimulation for IVF treatment, an observational preceding baseline natural cycle and a succeeding follow-up visit. Participants were enrolled between August 2016 and November 2018. Data from the randomized, stimulated cycle were part of a larger RCT, which was previously published. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public fertility clinic at Herlev Hospital, Denmark, including 31 healthy, normo-responding women eligible for IVF treatment. They underwent a natural baseline cycle and were subsequently randomized to receive either LZ 5 mg (n = 16) or placebo (n = 15) daily during ovarian stimulation from cycle day (CD) 2-3 until induction of ovulation. Throughout both cycles, monitoring was performed every third day with transvaginal ultrasound for assessment of follicle count and diameter, and blood analyses for the determination of twelve endocrine and paracrine parameters. A follow-up assessment was performed at CD2-3 in the succeeding cycle. In the randomized part of the study, we determined differences in blood parameters, follicle recruitment, and follicle diameter. In the observational part of the study, we assessed follicle recruitment in between cycles and its correlation to endocrine parameters. MAIN RESULTS AND THE ROLE OF CHANCE: Letrozole cotreatment significantly suppressed oestradiol (E2) concentrations in the follicular phase (area under the curve (AUC)-58% (95% CI [-70%;-43%], P < 0.001)) and luteal phase (AUC-39% [-63%;-1%], P = 0.046). This had a marked effect on the endocrine and paracrine output with increased follicular phase luteinizing hormone (AUC +37% [3%; 82%], P = 0.033), androstenedione (AUC +36% [6%; 74%], P = 0.016), testosterone (AUC +37% [7%; 73%], P = 0.013) and 17-OH-progesterone (AUC +114% [10%; 318%], P = 0.027). Furthermore, follicle-stimulating hormone (FSH) was increased at stimulation day 5 in the LZ group (P < 0.05). In the luteal phase, increased corpus luteum output was reflected by elevated progesterone (AUC +44% [1%; 104%], P = 0.043), inhibin A (AUC +52% [11%; 108%], P = 0.011), androstenedione (AUC +31% [9%; 58%], P = 0.006) and testosterone (AUC +29% [6%; 57%], P = 0.012) in the LZ group. The altered balance between oestrogens and androgens was reflected in a markedly reduced SHBG concentration in the LZ group throughout the luteal phase (AUC-35% [-52%;-11%], P = 0.009). Endocrine and paracrine parameters were similar between groups at the follow-up visit. Letrozole cotreatment significantly increased the mean number of follicles >16 mm at oocyte retrieval (7.2 vs 5.2, difference: 2.0, 95% CI [0.1; 3.8], P = 0.036), while the mean total number of follicles at oocyte retrieval was the same (23.7 vs 23.5, difference: 0.2 [-5.8; 6.1], P = 0.958), and the mean FSH consumption during the stimulated cycle was similar (1500 vs 1520 IU, difference-20 IU [-175; 136], P = 0.794). Between cycles, the mean antral follicle count at CD2-3 was unchanged (natural cycle 19.0, stimulated cycle 20.9, follow-up cycle 19.7, P = 0.692) and there was no effect of LZ cotreatment on the recruitment of the next follicle cohort (test for interaction, P = 0.821). LIMITATIONS, REASONS FOR CAUTION: This study included a relatively small, selected oup of healthy women with an expected normal ovarian function and reserve, and the effects of LZ may therefore be different in other patient groups. WIDER IMPLICATIONS OF THE FINDINGS: We confirm some previous findings concerning increased follicle growth and increased endogenous FSH and androgen production, which support the rationale for further studies on the use of LZ cotreatment, for example, as a form of endogenous androgen priming sensitizing the follicle to FSH. Letrozole appears to improve the luteal phase with better stimulation of corpus luteum and progesterone secretion. STUDY FUNDING/COMPETING INTEREST(s): The authors declare no conflicts of interest relating to the present work. TRIAL REGISTRATION NUMBER: NCT02939898.Copyright © 2022 The Author(s) 2022.

Pourfathi, H., et al. (2022). "The Effect of Intraoperative Oxytocin Infusion on Irrigation Fluid Absorption During Hysteroscopic Myomectomy: A Randomized Placebo-Controlled Double-Blind Trial." International Journal of Women's Health and Reproduction Sciences 10(3): 148-155.
	Objectives: One of the most prevalent benign tumors in women is uterine leiomyoma. Large quantities of fluid absorbed during myomectomy may cause serious problems such as volume overload and hyponatremia. The aim was to see how intraoperative oxytocin infusion affected irrigation fluid absorption in individuals having hysteroscopic myomectomy. Material(s) and Method(s): 50 women between 25-45 years who underwent hysteroscopic myomectomy and had an American Society of Anesthesiologists class I or II were evaluated in this randomized, double-blind clinical trial study. A 250 mL ringer solution containing 15 units of oxytocin was administered at a 125 mL/h in the oxytocin group (group S). In contrast, the placebo group (group P) received 1.5 mL of normal saline in the same amount of Ringer solution. Intraoperative hemodynamic alterations, fluid deficit, decreased hemoglobin, hematocrit, sodium, and albumin levels from baseline, complications, and the incidence of toxicity with the administered solutions were assessed intraoperative and 24 hours later. Result(s): Group S had considerably reduced irrigation fluid volume (P = 0.021) and volume deficit (P = 0.001). The frequency of hypotension in individuals receiving oxytocin did not differ significantly from the placebo group (P = 0.26). In group S, serum hematocrit (P = 0.036) and sodium (P = 0.026) were decreased significantly. Conclusion(s): Intraoperative oxytocin infusion during hysteroscopic myomectomy may be associated with reduced irrigation fluid absorption and the problems that come with it. As a result, this approach might decrease the risks associated with high amounts of irrigation fluid being absorbed during hysteroscopic myomectomy.Copyright © 2022 The Author(s).

Pourrahmat, M.-M., et al. (2021). "Health state utility values by cancer stage: a systematic literature review." The European journal of health economics : HEPAC : health economics in prevention and care 22(8): 1275-1288.
	Objectives: Cancer diagnoses at later stages are associated with a decrease in health-related quality of life (HRQOL). Health state utility values (HSUVs) reflect preference-based HRQOL and can vary based on cancer type, stage, treatment, and disease progression. Detecting and treating cancer at earlier stages may lead to improved HRQOL, which is important for value assessments. We describe published HSUVs by cancer type and stage.; Methods: A systematic review was conducted using Embase, MEDLINE ® , EconLit, and gray literature to identify studies published from January 1999 to September 2019 that reported HSUVs by cancer type and stage. Disutility values were calculated from differences in reported HSUVs across cancer stages.; Results: From 13,872 publications, 27 were eligible for evidence synthesis. The most frequent cancer types were breast (n = 9), lung (n = 5), colorectal (n = 4), and cervical cancer (n = 3). Mean HSUVs decreased with increased cancer stage, with consistently lower values seen in stage IV or later-stage cancer across studies (e.g., - 0.74, - 0.44, and - 0.51 for breast, colorectal, and cervical cancer, respectively). Disutility values were highest between later-stage (metastatic or stage IV) cancers compared to earlier-stage (localized or stage I-III) cancers.; Conclusions: This study provides a summary of HSUVs across different cancer types and stages that can inform economic evaluations. Despite the large variation in HSUVs overall, a consistent decline in HSUVs can be seen in the later stages, including stage IV. These findings indicate substantial impairment on individuals' quality of life and suggest value in early detection and intervention. (© 2021. The Author(s).)

Pourramezani, N., et al. (2022). "Comparison of the effects of acupressure and ice massage in primary dysmenorrhea: A randomized controlled trial." Journal of Experimental and Clinical Medicine (Turkey) 39(4): 1143-1149.
	The aim of the study was to compare the effectiveness of acupressure and ice massage treatment methods in the treatment of primary dysmenorrhea. The 210 female students were randomly divided into three groups: acupressure, ice massage and control. In the acupressure group, pressure was performed at the Hugo point by applying medium pressure for 10 minutes of massage. The procedure was repeated five times. In the ice massage group, 2 cm diameter circular ice pieces were used. Massage with ice was carried out rotationally for 10 minutes. Like the acupressure, the procedure was repeated five times. In the control group, glass marbles were applied at the Hugo point with no pressure and massage for 10 minutes. The intensity of pain was measured prior to the intervention, during the intervention and following the intervention using a visual analogue scale. In the beginning, the mean VAS scores were 7.41 +/- 1.82, 6.74 +/- 2.23, and 7.03 +/- 1.72 in the participants in groups control, acupressure and ice massage, respectively (P = 0.13). After the intervention, the mean pain scores were significantly lower at all of the time points in groups acupressure and ice massage than in group control participants (P < 0.001). Although the pain scores showed a more decreasing trend after the intervention in group ice massage than that in group acupressure, the difference between the two groups was not statistically significant (P = 0.97). It was revealed that treatment with acupressure and ice massage could also be recommended as a complementary medicine treatment for the treatment of primary dysmenorrhea with no reported side effects.Copyright © 2022 Ondokuz Mayis Universitesi. All rights reserved.

Pourteymour Fard, T., et al. (2021). "Changes of body composition and circulating neopterin, omentin-1, and chemerin in response to thylakoid-rich spinach extract with a hypocaloric diet in obese women with polycystic ovary syndrome: a randomized controlled trial." Phytotherapy research : PTR 35(5): 2594‐2606.
	This trial evaluated the effects of thylakoid‐rich spinach extract supplementation combined with a hypocaloric diet on body composition and serum levels of neopterin, chemerin, and omentin‐1 in obese women with polycystic ovary syndrome (PCOS). In this randomized controlled trial, 48 obese women with PCOS, aged 20–45 years old, were recruited and randomly divided into thylakoid (n = 24) and placebo (n = 24) groups. They received a low‐calorie diet with 5 g/day thylakoid‐rich spinach extract or a low‐calorie diet with 5 g/day placebo for 12 weeks. The mean age of the participants of the thylakoid group was 31.86 years, and the placebo group was 32.04 years. Thylakoid‐rich spinach extract supplementation with a low‐calorie diet increased serum levels of omentin‐1 (10.90 vs. 3.87 ng/L; p <.001) and decreased fat mass (−5.19 vs. −1.35 kg; p <.001) and serum levels of neopterin (−0.66 vs. −0.38 nmol/L; p =.003) and chemerin (−41.24 vs. −11.26 ng/L; p <.001) in the thylakoid group compared to the placebo group. A significant improvement in omentin‐1, chemerin, and neopterin by thylakoid‐rich spinach extract supplementation was under the influence of weight change and insulin resistance status throughout the study. A significant decrease in the other anthropometric indices and insulin resistance was also observed in the thylakoid group, compared to the placebo group (p <.001, for all parameters). Thylakoid‐rich spinach extract combined with a low‐calorie diet increased circulating omentin‐1 and decreased fat mass, abdominal obesity, as well as circulating chemerin, neopterin, and insulin in obese women with PCOS.

Pourteymour Fard, T., et al. (2020). "Quercetin and polycystic ovary syndrome, current evidence and future directions: a systematic review." Journal of Ovarian Research 13(1): 11.
	Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder and the most common gynecological endocrinopathy among reproductive-aged women. Current remedies are often used only to control its signs and symptoms, while they are not thoroughly able to prevent complications. Quercetin is an herbal bioactive flavonoid commonly used for the treatment of metabolic and inflammatory disorders. Thus, this systematic review was conducted to evaluate the efficacy of quercetin supplementation in subjects with PCOS. Databases until March 2019 were searched. All human clinical trials and animal models evaluating the effects of quercetin on PCOS women were included. Out of 253 articles identified in our search, 8 eligible articles (5 animal studies and 3 clinical trials) were reviewed. The majority of studies supported the beneficial effects of quercetin on the ovarian histomorphology, folliculogenesis, and luteinisation processes. The effects of quercetin on reducing the levels of testosterone, luteinizing hormone (LH), and insulin resistance were also reported. Although quercetin improved dyslipidemia, no significant effect was reported for weight loss. It is suggested that the benefits of quercetin may be more closely related to antioxidant and anti-inflammatory features of quercetin rather than weight-reducing effects. Therefore, this review article provides evidence that quercetin could be considered as a potential agent to attenuate PCOS complications. However, due to the paucity of high-quality clinical trials, further studies are needed.

Poveda, A., et al. (2022). "Olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer patients without a germline BRCA1/BRCA2 mutation: OPINION primary analysis." Gynecologic Oncology 164(3): 498-504.
	Objective: The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy.; Methods: In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose.; Results: Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6-10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively.; Conclusion: Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Powell, J. G., et al. (2020). "Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression." Annals of Pharmacotherapy 54(2): 157-163.
	Objective: To review the safety and efficacy of brexanolone for the treatment of moderate to severe postpartum depression (PPD). Data Sources: A literature search through PubMed was conducted (January 2012 to July 2019) using the keyword brexanolone for clinical trials published in the English language. Study Selection and Data Extraction: Articles were selected if they were related to the Food and Drug Administration (FDA) approval of brexanolone or provided novel clinical information regarding this drug entity. Data Synthesis: The findings of the review show that brexanolone administered via IV infusion is both an effective and a fairly safe option for the treatment of PPD. Relevance to Patient Care and Clinical Practice: There are several antidepressants currently used to treat PPD; however, this is the first with FDA approval for this indication. The rapid onset of action of brexanolone may offer a quicker relief of these symptoms and may possibly lead to improved quality of life for both the mother and the child. Conclusion and Relevance: The recent FDA approval of brexanolone may offer an effective treatment of moderate to severe PPD and has been shown to rapidly decrease depression symptoms.Copyright © The Author(s) 2019.

Powell Simon, G., et al. (2023). "Vascularisation in Deep Endometriosis: A Systematic Review with Narrative Outcomes." Cells 12(9).
	Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.

Prabhakar, P., et al. (2021). "Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 37(4): 332-336.
	PURPOSE: To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS: Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS: Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS: Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.

Pradnyana, I. W. A. S., et al. (2023). "The Role of Hysteroscopy in Patients with Recurrent Implantation Failure Before Starting In-Vitro Fertilization: A Systematic Review and Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	
Praiss Aaron, M., et al. (2023). "Morbidity after secondary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for ovarian cancer: An analysis of a randomized phase II trial." Gynecologic Oncology 171: 23-30.
	Objective: To assess postoperative complications after secondary cytoreductive surgery (SCS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), we conducted an exploratory analysis of patients with platinum-sensitive recurrent ovarian cancer enrolled in a randomized phase II trial.; Methods: Complications occurring within 30 days of surgery were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; only hemoglobin and platelet levels were assessed. Patients were grouped by CTCAE grade ≥ 3 and < 3 complications.; Results: Among 83 eligible patients, 33 (40%) had grade ≥ 3 complications and 50 (60%) had grade < 3 complications; anemia and abdominal infections were the most common. There were no perioperative mortalities. Time to initiation of postoperative chemotherapy for patients with grade ≥ 3 and grade < 3 events was 34 days (range, 18-60) and 31 days (range, 21-43), respectively (P = .017). Median progression-free survival (PFS) did not significantly differ between patients with grade ≥ 3 and grade < 3 complications (11.2 months [95% CI: 9.3-14.4] vs 14.9 months [95% CI: 11.3-16.5], respectively; P = .186), nor did median overall survival (OS) (46.9 months [95% CI: 34-NE] vs 68.2 months [95% CI: 52.1-NE], respectively; P = .053).; Conclusion: Postoperative complications following SCS with or without HIPEC were associated with slight delays in chemotherapy initiation but did not significantly impact oncologic outcomes. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prakasini, S., et al. (2024). "Occurrence and Drug Susceptibility of Candida Species in Cancer Cases: a systematic Review and Meta-analysis."
	
Prayitno Gunawan, D., et al. (2022). "Potential of Mesenchymal Stem Cells and Their Secretomes in Decreasing Inflammation Markers in Polycystic Ovary Syndrome Treatment: A Systematic Review." Medicines (Basel, Switzerland) 10(1).
	Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40-80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS , mesenchymal stem cells , and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors.

Precigen, I. and C. Institute National (2024). PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer.
	No Results Available Biological: PRGN-2009 plus Pembrolizumab|Drug: Pembrolizumab alone Determine the Objective Response Rate (ORR) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer.|Safety of PRGN-2009 in combination with pembrolizumab or pembrolizumab alone|Progression-Free Survival (PFS) and Overall Survival (OS) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone|Best Overall Responses (BOR) and Disease Control Rate (DCR) per RECIST v1.1 following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone|Time to Response and Duration of Responses following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone|Vector shedding following subcutaneous administration of PRGN-2009 All Phase 2 46 Industry|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment PRGN-2009-201 January 30, 2028

Preminger, B. A., et al. (2020). "A Systematic Review of Nonsurgical Vulvovaginal Restoration Devices: An Evidence-Based Examination of Safety and Efficacy." Plastic and reconstructive surgery 146(5): 552e-564e.
	Background: The efficacy and safety of vulvovaginal restoration devices were called into question in a U.S. Food and Drug Administration statement on July 30, 2018, claiming that women are being harmed by laser and other energy-based devices. The goal of this systematic literature review was to assess existing data, determine gaps in evidence, and propose opportunities for continued investigation pertaining to laser and energy-based vaginal restoration techniques.; Methods: A review of literature using PubMed, Cochrane Library databases, Embase, MEDLINE, and the Cumulative Index to Nursing and Allied Health Literature was conducted on January 9, 2019, and articles up to this point were considered. For inclusion, studies had to be available or translated in English and relate to clinical medicine, direct patient care, and nonsurgical energy-based vulvovaginal procedures.; Results: The authors found five level I studies, 19 level II studies, four level III studies, and 46 level IV studies that used 15 different devices. Various degrees of improvement of symptoms were reported in all studies. Adverse events/side effects were noted in two of the 13 radiofrequency device studies, 15 of the 23 erbium:yttrium-aluminum-garnet device studies, and 17 of the 37 carbon dioxide device studies. The majority of adverse events were considered mild.; Conclusions: The majority of studies resulted in mild to no adverse side effects. However, there is a large gap in level I evidence. As a result, the authors emphasize the necessity of supplemental data surrounding this subject and suggest that additional randomized sham-controlled studies be conducted to further investigate vulvovaginal restoration devices in an effort to address women's health issues.

Prentice, R. L., et al. (2021). "Randomized Trial Evaluation of the Benefits and Risks of Menopausal Hormone Therapy Among Women 50–59 Years of Age." American journal of epidemiology 190(3): 365‐375.
	The health benefits and risks of menopausal hormone therapy among women aged 50–59 years are examined in the Women's Health Initiative randomized, placebo‐controlled trials using long‐term follow‐up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy postmenopausal women aged 50–79 years at 40 US clinical centers during 1993–1998, including 10,739 post‐hysterectomy participants in a trial of conjugated equine estrogens and 16,608 participants with a uterus in the trial of these estrogens plus medroxyprogesterone acetate. Over a (median) 18‐year follow‐up period (1993–2016), risk for a global index (defined as the earliest of coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and all‐cause mortality) was reduced with conjugated equine estrogens with a hazard ratio of 0.82 (95% confidence interval: 0.71, 0.95), and with nominally significant reductions for coronary heart disease, breast cancer, hip fracture, and all‐cause mortality. Corresponding global index hazard ratio estimates of 1.06 (95% confidence interval: 0.95, 1.19) were nonsignificant for combined estrogens plus progestin, but increased breast cancer risk and reduced endometrial cancer risk were observed. These results, among women 50–59 years of age, substantially agree with the worldwide observational literature, with the exception of breast cancer for estrogens alone.

Prescott Lauren, S., et al. (2023). "Transfusion use and effect on progression-free, overall survival, and quality of life in upfront treatment of advanced epithelial ovarian cancer: evaluation of the European Organization for Research and Treatment EORTC-55971 Cohort." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(1): 1-9.
	Background: The impact of blood transfusion on ovarian cancer survival is uncertain.; Objective: To investigate whether peri-operative blood transfusion negatively impacted progression-free survival, overall survival, and quality of life in patients with advanced ovarian cancer.; Methods: We performed an ancillary analysis of the European Organization for Research and Treatment (EORTC) 55971 phase III trial, in which patients were randomized to primary debulking surgery versus neoadjuvant chemotherapy. Patients included in the per-protocol analysis were categorized by receipt of a transfusion.; Results: 612 of 632 (97%) of patients had adequate data for analysis. Of those, 323 (53%) received a transfusion. The transfusion cohort was more likely to have had better Word Health Organization (WHO) performance status, serous histology, undergone primary debulking surgery, and received more aggressive surgery, with higher rates of no gross residual disease. Median overall survival was 34.0 vs 35.2 months in the no transfusion and transfusion cohorts (p=0.97). The adjusted HR for death was 1.18 (95% CI 0.94 to 1.48) in favor of the transfusion cohort. Median progression-free survival was 13.6 vs 12.6 months in the no transfusion and transfusion cohorts (p=0.96). The adjusted HR for progression was 1.14 (95% CI 0.91 to 1.43). There were no significant differences in global quality of life, fatigue, dyspnea, or physical functioning between the two cohorts at baseline or at any of the four assessment times. Grade 3 and 4 surgical site infections were more common in the transfusion cohort.; Conclusion: Transfusion did not negatively impact progression-free survival or overall survival; however, it was associated with increased peri-operative morbidity without improvements in quality of life.; Competing Interests: Competing interests: RLC: grants from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen Janssen, Roche/Genentech; consulting fees from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen Janssen, OncoQuest, Onxeo, Onxerna, Regeneron, Roche/Genentech; participated in a data safety monitoring board or advisory board - VBL therapeutics. LSP: advisory board tempus, payment or honoraria for lectures from Clinical Care Options. CCS: research funding AstraZeneca; payment or honoraria from Ludemann Family Fund. IV: grants or contracts Amgen, Roche, Oncoinvent; consulting fees - Amgen (Europe) GmbH (2019), AstraZeneca (2019-2020), Clovis Oncology inc. (2019), Carrick Therapeutics (2019), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Immunogen Inc. (20192020), Mersana (2020), Millennium Pharmaceuticals (2019), MSD (2019-2020), Novocure (2020), Octimet Oncology (2019), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020) Deciphera Pharmaceuticals (2021), Jazzpharma (2021-2022), Oncoinvent AS (2021-2022); payment or honoraria - Agenus (2021), Aksebio (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2021-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); meeting support - Amgen, MSD, Tesaro, AstraZeneca, Roche advisory board - Agenus (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), MSD (2021-2022), Novocure (2021-2022), Novartis (2021), Seagen (2021), Sotio a.s. (2021-2022) (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Previato, L., et al. (2022). "Aspects of insulin metabolism in patients undergoing IVF: Literature review." Jornal Brasileiro de Reproducao Assistida 26(4): 700-701.
	Objective: Integrative literature review with the objective of evaluating whether hyperinsulinemia interferes with the ovary and, consequently, the ovulation process, oocyte quality and pregnancy rates in patients undergoing IVF, since insulin is an important modulator of follicular development, steroidogenesis, maturation oocyte and embryonic development. Method(s): Literature search was conducted in Pubmed and SciELO databases, using keywords: Insulin; hyperinsulinemia; fertility; infertility; polycystic ovary; metabolic syndrome; Assisted Human Reproduction; In vitro fertilization (IVF); ovary; oocyte quality and obesity. Studies in humans undergoing IVF treatment were selected. Inclusion criteria: Articles published in the last 10 years, original research, cross-sectional studies carried out in human population, with more than 30 patients and systematic reviews. Result(s): Of 237 studies reviewed, 39 were included in this review, being 30 retrospective and 9 prospective. The results obtained in this literature review showed that due to the high prevalence of obesity, especifically in women of reproductive age, there is a concern related to the risks to these women's fertility, due to the increased risk of type 2 diabetes, metabolic syndrome (MetS) and other noncommunicable diseases. The MetS is composed of hypertension, dyslipidemia, abdominal obesity and insulin resistance or glucose intolerance and has an adverse impact on female reproduction due to impaired endometrial receptivity and compromised embryonic development. Obesity is also associated with polycystic ovarian syndrome (PCOS), and many of the metabolic abnormalities of MetS also overlap with PCOS. About 50% to 70% of women with PCOS have insulin resistence and infertile women with PCOS had higher levels of fasting insulin, and the resultant hyperinsulinemia plays a role in the pathogenesis of reproductive disorders. Therefore, knowing that insulin has an action on both ovulation and oocyte quality, hyperinsulinemia implies impaired fertility, i.e., altering the ovulatory process, producing low-quality oocytes, probably due to increased inflammation and oxidation, in addition to disrupts the intrafollicular microenvironment during folliculogenesis and reduces the rate of fertilization and embryonic development potential during the natural and ovarian stimulation cycles. Obese women, when undergoing assisted reproduction techniques (ART), require higher doses of gonadotropins (Gn); have an altered follicular environment, poor or unpredictable ovarian response to hormonal stimulation; more cycles canceled; few granulosa cells and cumulus-oocyte complexes in egg as piration; more immature oocytes; fewer oocytes retrieved; abnormal morphology and spindle malformation; lower fertilization rates; incomplete or impaired embryonic development after ICSI/IVF; lower implantation and pregnancy rates and higher miscarriage rate; lower overall live birth rate after IVF compared to normal weight women. If they become pregnant, they have more gestational complications and risk of morbidity, spontaneous preterm birth, reduced rates of live births and greater chance of stillbirth, increased risk of complications during delivery, lower birth weight and health complications for babies. Conclusion(s): No studies have addressed how women are being counseled and understood about the effects of obesity on reproductive outcomes. An altered metabolic environment negatively affects reproductive outcomes before conception even occurs, therefore it is essential that intervention occurs in the pre-conception period. Thus, it is very important that they are guided about changes in habits, to control insulin levels, through a healthy diet, prioritizing foods rich in fiber and antioxidants, natural and whole, reducing or excluding ultra-processed foods, reduction of saturated fat, trans fat, in order to maintain adequate insulin and blood glucose levels. It is part of this process to include the practice of physical exercises in the daily routine, and weight control for those who a e overweight. This can increase fertility and the chances of pregnancy in patients undergoing IVF.

Priya, K., et al. (2022). "Effectiveness of physiotherapy interventions for the treatment of chronic pelvic pain associated with gynecological, urological and gastrointestinal conditions: a systematic review and meta-analysis of randomized controlled trials."
	
Proctor, D. N., et al. (2022). "Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women." Nitric oxide : biology and chemistry 122‐123: 26‐34.
	Exercise tolerance appears to benefit most from dietary nitrate (NO3‐) supplementation when muscle oxygen (O2) availability is low. Using a double‐blind, randomized cross‐over design, we tested the hypothesis that acute NO3‐ supplementation would improve blood flow restricted exercise duration in post‐menopausal women, a population with reduced endogenous nitric oxide bioavailability. Thirteen women (57‐76 yr) performed rhythmic isometric handgrip contractions (10% MVC, 30 per min) during progressive forearm blood flow restriction (upper arm cuff gradually inflated 20 mmHg each min) on three study visits, with 7‐10 days between visits. Approximately one week following the first (familiarization) visit, participants consumed 140 ml of NO3‐ concentrated (9.7 mmol, 0.6 gm NO3‐) or NO3‐depleted beetroot juice (placebo) on separate days (≥7 days apart), with handgrip exercise beginning 100 min post‐consumption. Handgrip force recordings were analyzed to determine if NO3‐ supplementation enhanced force development as blood flow restriction progressed. Nitrate supplementation increased plasma NO3‐ (16.2‐fold) and NO2‐ (4.2‐fold) and time to volitional fatigue (61.8 ± 56.5 s longer duration vs. placebo visit; p = 0.03). Nitrate supplementation increased the rate of force development as forearm muscle ischemia progressed (p = 0.023 between 50 and 75% of time to fatigue) with non‐significant effects thereafter (p = 0.052). No effects of nitrate supplementation were observed for mean duration of contraction or relaxation rates (all p > 0.150). These results suggest that acute NO3‐ supplementation prolongs time‐to‐fatigue and speeds grip force development during progressive forearm muscle ischemia in postmenopausal women.

Prodromidou, A., et al. (2019). "Short- and long term outcomes after abdominal radical trachelectomy versus radical hysterectomy for early stage cervical cancer: a systematic review of the literature and meta-analysis." Archives of Gynecology and Obstetrics 300(1): 25-31.
	Purpose: Cervical cancer (CC) ranks 2nd for mortality among women of reproductive age in the United States. Abdominal radical trachelectomy (ART) is a fertility sparing approach that has been proposed in women with early stage CC who wish to preserve their fertility. The aim of the present meta-analysis was to evaluate the short- and long-term outcomes of RH vs ART for early stage CC.; Methods: A total of 5 electronic databases were searched for articles published up to December 2018. Prospective and retrospective trials reporting outcomes for women who underwent ART or RH for the management of early stages CC, were considered eligible for inclusion. Statistical meta-analysis was performed using the RevMan 5.3 software.; Results: A total of 5 studies which included 840 women who underwent ART or radical trachelectomy (RH) were included in the present meta-analysis. Among them, 324 underwent ART whereas the remaining 516 had RH. Despite the fact that ART was associated with significantly prolonged operative time compared to RH (840 patients MD 36.82 min, 95% CI 20.15-53.49, p < 0.001), neither 5-year OS nor 5-year DFS were different among the two groups (714 patients OR 1.39, 95% CI 0.53-3.62, p = 0.51 and 682 patients OR 1.08, 95% CI 0.52-2.25, p = 0.84, respectively).; Conclusions: ART is a more complex and time consuming technique, but equally safe compared to RH in terms of oncological outcomes for selected women with early stage CC and allows for more CC survivors of childbearing age to preserve their fertility.

Prodromidou, A., et al. (2019). "The application of fibrin sealant for the prevention of lymphocele after lymphadenectomy in patients with gynecological malignancies: A systematic review and meta-analysis of randomized controlled trials." Gynecologic Oncology 153(1): 201-208.
	Purpose: The aim of the present study was to evaluate the correlation between the use of fibrin-collagen sealants on lymph node dissection areas and formation of lymphocele after lymphadenectomy in patients with gynecological malignancies.; Materials and Methods: A systematic search of 5 electronic databases for articles published up to November 2018 was performed. All randomized controlled clinical trials (RCTs) which reported outcomes after application of fibrin collagen agents in patients who underwent lymphadenectomy for gynecological malignancies, were finally included in the present meta-analysis. Statistical meta-analysis was performed using the RevMan 5.3 software.; Results: A total of 6 RCTs which recruited 481 patients were included in the present study. Meta-analysis revealed significantly decreased total amount of drained fluid and of mean duration of drainage in fibrin sealant group when compared to control, (187 patients MD -86.40 ml 95% CI -100.2 to -72.60 p < 0.00001 and 113 patients MD -1.00 days 95% CI -1.13 to -0,87 p < 0.00001, respectively). No difference in overall incidence of lymphocele and in the incidence of symptomatic ones among the two groups was observed (592 cases OR 0.61 95% CI 0.36 to 1.05 p = 0.08, and 444 cases OR 0.59 95% CI 0.26 to 1.35 p = 0.22, respectively).; Conclusions: The present meta-analysis supports the safety of the use of fibrin sealants in women undergoing pelvic and/or para-aortic lymphadenectomy due to gynecologic cancer but its benefit remains uncertain. It was found effective in reducing the duration and volume of drainage, but it was not associated with difference in the incidence of lymphocele. Further studies are required to confirm our conclusion and broaden our knowledge about its impact on other parameters. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prodromidou, A., et al. (2020). "Safety and efficacy of synchronous panniculectomy and endometrial cancer surgery in obese patients: a systematic review of the literature and meta-analysis of postoperative complications." Journal of the Turkish German Gynecological Association 21(4): 279-286.
	Panniculectomy combined with gynaecological surgery constitutes an alternative approach for endometrial cancer (EC) in obese patients. The present study aimed to assess the current knowledge concerning the safety and efficacy of combining panniculectomy in surgical management of EC. Four electronic databases were systematically searched for articles published up to May 2019. A total of five studies, of which two were non-comparative and three comparative, were included. Meta-analysis of complications among panniculectomy and conventional laparotomy group revealed no difference in either intra- or post-operative complication rates. Moreover, no difference was reported in surgical site complications (p=0.59), while wound breakdown rates were significantly elevated in the laparotomy group (p=0.02). Panniculectomy combined surgery for the management of EC appears to be a safe procedure and results in comparable outcomes compared with conventional laparotomy with regard to complications and improved wound breakdown rates.

Prodromidou, A., et al. (2021). "The evolving role of targeted metformin administration for the prevention and treatment of endometrial cancer: A systematic review and meta-analysis of randomized controlled trials." Journal of Gynecology Obstetrics and Human Reproduction 50(9): 102164.
	Aim: The aim of the present study was to evaluate the role of metformin in endometrial cancer (EC), focusing on its potential preventive effect in breast cancer and obese patients and its safety and efficacy when added to progesterone monotherapy in EC patients who wish to preserve their fertility.; Methods: We reviewed the literature and then conducted a meta-analysis of the relevant parameters.; Results: A total of 6 studies was included in the meta-analysis. Regarding the pre-surgical treatment with metformin versus placebo, meta-analysis of mean difference in Ki-67 after treatment among two groups, revealed no difference (MD -7.10, 95% CI -23.31 to 9.11, p = 0.39). Meta-analysis of fertility sparing EC management with a combination of megestrol acetate (MA) and metformin (500 mg three times a day) in comparison with monotherapy with 160 mg daily MA revealed no difference in either complete response or partial response rates (166 patients OR 2.94, 95% CI 0.85 to 10.15, p = 0.09 and 166 patients OR 0.76, 95% CI 0.34 to 1.66, p = 0.49, respectively). As far as breast cancer survivors under tamoxifen are concerned, metformin was associated with significantly reduced median endometrial thickness after 52 weeks of evaluation compared to women in placebo group (2.3 mm vs 3.0 mm, p = 0.05).; Conclusions: Metformin neither was found to be an anti-proliferative agent against the development of endometrial cancer nor beneficial in addition to the progesterone monotherapy for EC fertility sparing candidates. However, a protective effect of metformin was demonstrated in breast cancer survivors under tamoxifen. Clinical outcomes of the ongoing trials are warranted to evaluate the therapeutic use of metformin in EC. (Copyright © 2021. Published by Elsevier Masson SAS.)

Prodromidou, A., et al. (2020). "The Emerging Role of Neutral Argon Plasma (PlasmaJet) in the Treatment of Advanced Stage Ovarian Cancer: A Systematic Review." Surgical innovation 27(3): 299-306.
	Objective . To evaluate the contribution of PlasmaJet application in achieving optimal cytoreduction in advanced ovarian cancer. Methods . We systematically searched for articles published up to June 2019 using MEDLINE, Scopus, Google Scholar databases and clinicaltrials.gov along with the references of the articles retrieved in full text. Observational studies and case reports addressing cases of women with peritoneal spread due to advanced stage ovarian cancer who were treated with application of PlasmaJet device were considered eligible for inclusion. Results . Three studies were excluded from further analysis when they were retrieved in full text. Five studies (2 retrospective, 1 prospective, and 2 case reports) that comprised 77 patients with age range from 38 to 85 years were included. Forty-three women underwent interval debulking surgery, 24 patients primary debulking surgery, and 6 had optimal debulking surgery, while in the remaining 4, a secondary debulking surgery was performed. Incidence of intraoperative complications was 32% (8/25), but none of them was due to the application of PlasmaJet. Complete macroscopic resection was achieved in 59 out of 70 (84.3%) women. Postoperatively, 17 out of 72 patients (23.6%) developed complications such as pneumothorax due to diaphragmatic resection, systemic infections, or wound-related complications. No postoperative mortality was recorded. Conclusions . Preliminary data on the use of PlasmaJet for ablation of ovarian cancer implants in the peritoneal cavity showed its safety and presented with promising outcomes in achieving complete cytoreduction.

Prodromidou, A., et al. (2022). "Clinicopathological characteristics and survival outcomes of patients with large cell neuroendocrine carcinoma of the uterine cervix: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 270: 212-220.
	Purpose: Large cell neuroendocrine carcinoma (LCNEC) of the cervix represents a rare tumour entity associated with poor prognosis. Knowledge about carcinogenesis and therapeutic options is scarce, while novel therapeutic targeted approaches are limited.; Methods: We performed a systematic review of four electronic databases from inception to June 2020. Eligible studies included all reports that addressed survival outcomes of women with LCNEC.; Results: A total of 31 case studies including 87 LCNEC patients were identified. Median patients' age was 41 years (range: 21-81). Most women (76.3%) had FIGO stage I-II disease. Overall, 72.0% had surgery, 70.1% received chemotherapy and 50.7% received radiotherapy. Of 13 patients with known HPV-status, 15% were HPV negative. Median overall survival (OS) was 24 months (range: 0.5-151), with 3- and 5-year OS of 42% and 29%, respectively. In multivariate analyses, only surgery and lymphadenectomy significantly associated with survival (Surgery OS: HR 0.14; 95% C.I:0.03-0.71, p = 0.018 / Surgery PFS: HR 0.23, 95% C.I. 0.06, 0.92, p = 0.037 / Lymphadenectomy OS: HR 0.26, 95% C.I. 0.07-0.98, p = 0.046 / Lymphadenectomy PFS: HR 0.30, 95% C.I. 0.09-0.98, p = 0.046). Age, chemotherapy or radiotherapy did not significantly impact survival, but lower stage was associated with improved survival.; Conclusion: Cervical LCNECs overall have a poor prognosis, despite their relatively early-stage initial presentation. Surgery and lymphadenectomy appear to significantly affect survival in contrast to chemotherapy and radiotherapy, which appear to have no significant effect on prognosis. Prospective multicentre cancer registries are warranted to improve treatment options for this rare disease. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Prodromidou, A., et al. (2020). "Robotic versus laparoendoscopic single-site hysterectomy: a systematic review and meta-analysis." Journal of Robotic Surgery 14(5): 679-686.
	Single-site hysterectomy (SSH) laparoscopic or robotic presented distinct advantages with regards to postoperative cosmetic outcome, wound-related complications and morbidity. We aimed to evaluate the feasibility of robotic and laparoscopic SSH in patients with benign or early-stage malignant gynecological conditions and to compare the two approaches. A systematic search of four electronic databases for articles published up to September 2019 was performed. Studies reporting outcomes for women who underwent robotic or laparoscopic SSH were considered eligible. A total of 6 studies with 412 patients were included. Among them, 150 women had robotic SSH, whereas 262 had laparoscopic SSH. Neither total operative time nor total hysterectomy time were found different among the 2 groups (355 patients MD 17.47 min, 95% CI - 5.82 to 40.76, p = 0.14 and 285 patients MD 6.41 min, 95% CI - 10.24 to 23.06, p = 0.45, respectively). Robotic approach presented significantly lower blood loss and hospital stay compared to laparoscopic (287 patients MD - 10.84 ml 95% CI - 20.35 to - 1.32, p = 0.03, 328 patients MD - 0.32 days, 95% CI - 0.44 to - 0.19, p < 0.00001, respectively). No difference was found with regards to major or overall postoperative complications. The present meta-analysis supports the use of robotic SSH, since it was related to faster recovery and comparable operative times and complication rates compared to laparoscopic. Nonetheless, due to the limited number of the included studies and their retrospective nature, the aforementioned outcomes must be interpreted with caution and further larger volume studies are needed in the field.

Prodromidou, A., et al. (2021). "Fertility sparing surgery for early-stage clear cell carcinoma of the ovary; A systematic review and analysis of obstetric outcomes." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47(6): 1286-1291.
	Clear cell carcinoma of the ovary (CCOC), accounts for 5-25% of epithelial ovarian cancer (EOC) cases. A significant proportion of patients with CCOC are of reproductive age, wishing to preserve their fertility. The application of fertility sparing surgery (FSS) in those patients has been extensively criticized, due to the high reported recurrence rates and chemotherapy resistance. The aim of the present study was to accumulate the current knowledge on obstetric and fertility outcomes of patients with early stage CCOC who underwent fertility sparing surgery. A meticulous search of 3 electronic databases was conducted for articles published up to June 2020 relevant in the field using the terms "ovarian cancer", "clear cell", "fertility sparing", "conservative treatment". Studies that reported pregnancy and maternal outcomes after fertility sparing surgery for the management of early stage CCOC were considered eligible. A total of 5 studies which comprised of 60 patients with early stage CCOC, who underwent fertility-sparing surgery, were reviewed. Ten patients (16.6%) had disease recurrence. The total clinical pregnancy rate of 32% with a proportion of 24% of live birth rates in 12 of the included patients. The median interval from surgery to pregnancy was 41.5 months, while no evidence of disease was recorded among the patients who achieved pregnancy. No difference in survival and recurrence rates among patients who underwent fertility-sparing surgery and those who had radical surgical procedures. Fertility-sparing treatment for International Federation of Gynaecology and Obstetrics (FIGO) Stage IA/IC CCOC seems to be an acceptable treatment option for selected premenopausal women who strongly wish to preserve their childbearing potential. However, larger studies are needed to validate the safety of the procedure.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Prodromidou, A., et al. (2022). "The Emerging Role on the Use of Platelet-Rich Plasma Products in the Management of Urogynaecological Disorders." Surgical innovation 29(1): 80-87.
	Background : The regenerative efficacy of platelet-derived products has been recently investigated in the treatment of pelvic floor disorders (PFDs). We aimed to synthesize the current evidence of platelet-rich plasma (PRP) products used in urogynaecological disorders including vaginal atrophy, pelvic organ prolapse (POP), urinary incontinence, vaginal fistulas and vaginal mesh exposure. Methods : A meticulous search of the currently available literature on the use of PRP for the management of PFDs was performed using 3 electronic databases. Results : PRP could be a feasible alternative modality for the management of vaginal atrophy with favourable outcomes in vaginal atrophy parameters and patients' satisfaction, especially when hormone therapy is contraindicated. In patients with POP, an increase in collagen concentration after PRP application was observed while the use of PRP resulted in improvement of stress urinary incontinence symptoms. A considerable proportion of vesicovaginal fistulas were treated after application of PRP-based injections. Conclusions : There is only limited evidence of the use of PRP for PFDs. Platelet-rich plasma appears to be a promising, easy to apply, cost-effective and feasible alternative therapeutic modality for the management of various urogynaecological disorders. Future randomized trials are needed to confirm the efficacy of PRP in the treatment of urogynaecological disorders.

Prom, M. C., et al. (2022). "A Systematic Review of Interventions That Integrate Perinatal Mental Health Care Into Routine Maternal Care in Low- and Middle-Income Countries." Frontiers in Psychiatry 13: 859341.
	Background: Women in low- and middle-income countries (LMICs) are disproportionally affected by perinatal depression and anxiety and lack access to mental health care. Integrating perinatal mental health care into routine maternal care is recommended to address gaps in access to mental health care in such under-resourced settings. Understanding the effectiveness of interventions that integrate perinatal mental health care into routine maternal care in LMICs is critical to inform ongoing intervention development, implementation, and scale-up. This systematic review aims to assess the effectiveness of interventions that integrate perinatal mental health care into routine maternal care to improve maternal mental health and infant health outcomes in LMICs. Method(s): In accordance with the PRISMA guidelines, an electronic database search was conducted seeking publications of controlled trials examining interventions that aimed to integrate perinatal mental health care into routine maternal care in LMICs. Abstracts and full text articles were independently reviewed by two authors for inclusion utilizing Covidence Review Software. Data was extracted and narrative synthesis was conducted. Finding(s): Twenty studies met eligibility criteria from the initial search results of 2,382 unique citations. There was substantial heterogeneity between the study samples, intervention designs, and outcome assessments. Less than half of the studies focused on women with active depression or anxiety. Most studies (85%) implemented single intervention designs involving psychological, psychosocial, psychoeducational, or adjuvant emotion/stress management. There were few interventions utilizing multicomponent approaches, pharmacotherapy, or referral to mental health specialists. Outcome measures and assessment timing were highly variable. Eighteen studies demonstrated significantly greater improvement on depression and/or anxiety measures in the intervention group(s) as compared to control. Conclusion(s): Integrated interventions can be effective in LMICs. The findings provide a critical understanding of current interventions design gaps. This includes the lack of comprehensive intervention designs that incorporate increasing intensity of treatment for more severe illness, pharmacotherapy, mental health specialist referrals, and non-mental health professional training and supervision. The findings also provide strategies to overcome design and implementation barriers in LMICs. Study findings provide a foundation for future evidence-based adaptation, implementation, and scale-up of interventions that integrate perinatal mental health care into routine maternal care in LMICs. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_ record.php?ID=CRD42021259092], identifier [CRD42021259092].Copyright © 2022 Prom, Denduluri, Philpotts, Rondon, Borba, Gelaye and Byatt.

Psilopatis, I., et al. (2023). "The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy." International Journal of Molecular Sciences 24(15).
	Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

Psilopatis, I., et al. (2023). "The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities." Cells 12(9).
	Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the particular role of HDACs and their inhibitors in the context of endometriosis. HDAC1, HDAC2, HDAC3, Sirtuin 1, and Sirtuin 3, are the five most studied HDAC enzymes which seem to, at least partly, influence the pathophysiology of endometriosis. Both well-established and novel HDACIs could possibly represent modern, efficacious anti-endometriotic drug agents. Altogether, histone modifications and their therapeutic targeting have been proven to have a strong impact on endometriosis.

Psilopatis, I., et al. (2023). "The Role of Bitter Melon in Breast and Gynecological Cancer Prevention and Therapy." International Journal of Molecular Sciences 24(10).
	Phytotherapy has long represented a widely accepted treatment alternative to conventional therapy. Bitter melon is a vine with potent antitumor effects against numerous cancer entities. To date, no review article has, however, been published on the role of bitter melon in breast and gynecological cancer prevention and therapy. The current work constitutes the most comprehensive, up-to-date review of the literature, which highlights the promising anticancer effects of bitter melon on breast, ovarian, and cervical cancer cells and discusses future research recommendations.

Psilopatis, I., et al. (2023). "The Role of Peroxisome Proliferator-Activated Receptors in Polycystic Ovary Syndrome." Journal of Clinical Medicine 12(8).
	Polycystic ovary syndrome (PCOS) constitutes the most common endocrine disorder in women of reproductive age. Patients usually suffer from severe menstrual irregularities, skin conditions, and insulin resistance-associated health conditions. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins that regulate gene expression. In order to investigate the role of PPARs in the pathophysiology of PCOS, we conducted a literature review using the MEDLINE and LIVIVO databases and were able to identify 74 relevant studies published between 2003 and 2023. Different study groups reached contradictory conclusions in terms of PPAR expression in PCOS. Interestingly, numerous natural agents were found to represent a novel, potent anti-PCOS treatment alternatives. In conclusion, PPARs seem to play a significant role in PCOS.

Psomiadou, V., et al. (2021). "Is minimal invasive surgical treatment of ovarian cancer plus HIPEC a utopia? A review of the literature." European Journal of Gynaecological Oncology 42(5): 1001-1005.
	The purpose of this study is to evaluate the effectiveness and safety of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) approached by minimally invasive surgical (MIS) techniques. We conducted a systematic review of the published relevant studies and evaluated a total of 403 patients, with a median age of 57 years old (20-69). The histology of the patients included 160 (39.7%) patients with pseudomyxoma peritonei, 43 (10.6%) with mesothelioma peritonei, 37 (9.2%) with epithelial ovarian cancer (EOC), 80 (19.8%) with appendiceal cancer and 26 (6.4%) with colon cancer, while the histology of the rest of the patients was not specified in the studies. The median Periotoneal Cancer Index (PCI) was 4 (1-10) and complete cytoreduction (R0) was achieved in 239 patients (60%). 145 (36%) of the patients underwent omentectomy, 37 patients (9.2%) underwent cecum/right colectomy, 41 patients (10.1%) underwent salpingovariectomy, 6 (1.5%) small bowel resection, 28 (6.7%) peritonectomies, in 9 (2.2%) sigmoeidectomy and 107 (26.5%) appendectomy, with a mean operative time of 240 min (90-510). Conversion to laparotomywas performed in 13 (3.2%) cases, while in 32 (7.9%) an intestinal anastomosis or suture was required. The median length of stay was 4.5 days (3-6) and the median follow-up of the patients was 13.5 months (1-72). We concluded that minimal invasive surgery can be considered as an approach in the application of hyperthermic intraperitoneal chemotherapy. Further large studies with higher quality data are warranted to verify our findings.Copyright ©2021 The Author(s). Published by IMR Press.

Psomiadou, V., et al. (2022). "Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treatment of advanced ovarian cancer. A review of the literature." European Journal of Gynaecological Oncology 43(1): ejgo4301004.
	Objective: The majority of advanced ovarian cancer (OC) patients do not fully respond to systemic chemotherapy, thus complete cytoreduction can not be achieved in such cases. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been suggested as an alternative approach for these women. Our study aimed to review the literature regarding the application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in OC patients with peritoneal carcinomatosis (PC). Data source: Articles in the English language were searched in PubMed. Search terms included "PIPAC" and "ovarian cancer". Methods of study selection: The authors evaluated all studies presenting an application of pressurised intraperitoneal aerosol chemotherapy (PIPAC) on ovarian cancer patients. The published guidelines for Systematic Reviews and Meta-analyses (PRISMA) were followed in the present systematic review which was performed based on the authors' predetermined inclusion criteria. Tabulation: Table 1 presents the main characteristics and outcomes of the OC patients undergoing PIPAC. Integration: Study selection and data extraction were independently undertaken by two reviewers. Result(s): 235 patients from 15 studies retrieved from PubMed were included. Conclusion(s): Our results indicate that PIPAC is efficient and safe in selected OC patients with PC not responding to systemic chemotherapy. The toxicity is manageable and the quality of life sustained. Further, randomised controlled trials are warranted to confirm our findings.Copyright: © 2022 The Author(s). Published by IMR Press. This is an open access article under the CC BY 4.0 license.

Psomiadou, V., et al. (2021). "Robotic interval debulking surgery for advanced epithelial ovarian cancer: current challenge or future direction? A systematic review." Journal of Robotic Surgery 15(2): 155-163.
	We evaluated the effectiveness, safety and efficacy of robotic interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NACT). We conducted a systematic review of the published relevant studies. Α total of 102 patients were evaluated. Mean operative time ranged from 164 to 312 min (mean ± SD: 246 ± 61 min) while mean estimated blood loss ranged from 106.9 to 262.5 ml (mean ± SD: 168 ± 68 ml) and postoperative blood transfusion rate was 19% (n = 19/98). Complete cytoreduction rate (R0 resection) was achieved in 75 patients (76.5%), whereas residual disease ≤ 1 cm in 21 women (21.5%). Mean hospital stay was 2.4 days. No intraoperative and six postoperative (14.6%) complications were reported. Laparotomy conversion rate was 9.2% (9/98) mostly in the terms of achieving complete cytoreduction and 30-day mortality rate was 9.2% (n = 9/98). The median overall survival varied from 39.7 to 47.2 months, while the progression-free survival ranged from 20.6 to 21.2 months during a median follow-up period from 2 to 86 months (median 25.3 months). A total of 60 women (61%) developed disease recurrence. One of the studies reported significantly improved OS and PFS in patients who underwent robotic IDS when compared to those who had laparotomy either during or before the addition of robotic surgery in the management of advanced ovarian cancer disease (47.2 vs 37.8 vs 37.9, p = 0.004 for OS and 20.6 vs 13.9 vs 11.9, p = 0.005 for PFS, respectively). The same was also observed when controlling the parameters of age and stage for patients in the robotic arm (p = 0.02). Robotic interval debulking surgery can be considered in the management of advanced ovarian cancer patients after receiving neoadjuvant chemotherapy. Larger meta-analyses including multicenter randomized control trials are necessary to specify the exact profile of the patients that could benefit from this treatment strategy.

Pszczolkowska, B., et al. (2022). "The influence of the used applicators on organ and target doses for cervical cancer patients treated with HDR brachytherapy." Polish Journal of Medical Physics and Engineering 28(3): 139-149.
	Introduction: The aim of this work was to study the influence of the applicators used for cervical cancer patients treated with high dose-rate brachytherapy (HDR-BT) in the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland on doses in the tumour volumes and organs at risk. Material(s) and Method(s): The treatment was carried out using Iridium-192 in 4 fractions (7.5 Gy each) given in weekly intervals. Two types of applicators were used for comparison: fletcher and ring. The standard dose distribution parameters, read from the system Oncentra Brachy (version 4.5, Elekta), for bladder, rectum, and sigmoid (D2 cc) and tumour (HRCTV D100, D98, D90) were studied. Patients were divided into two groups (240 treatment plans) depending on the type of applicator used and into four groups according to the tumour volumes (HR-CTV < 25 cm3 or HR-CTV >= 25 cm3). The collected data were analysed using the PQStatSoftware (version 1.8.2). Result(s): The treatment plans prepared with all types of applicators fulfil the dose distribution requirements, however, the dose delivered to the tumour using the ring applicator was found to be the highest. For the bladder and sigmoid the optimal dose distribution was obtained when using the fletcher applicator, while for the rectum the ring applicator gave the smallest dose value. The D2 cc parameter for sigmoid obtained for fletcher treatment has smaller values in the case of patients with small tumour volume and for this type of applicator was observed a statistically significant difference when compared with the ring. Conclusion(s): The ring applicator gives the optimal parameters of the dose distribution independently on the tumour volume with respect to the fletcher applicator, which is however more often used in clinical practice.Copyright © 2022 Beata Pszczolkowska et al., published by Sciendo.

Pu, T., et al. (2023). "Comparative analysis of fractional CO2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions." Journal of Chinese Physician 25(3): 406-410.
	Objective To investigate the effects of fractional CO2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions. Methods A prospective study was conducted on 126 patients with white lesions of the vulva admitted to Hainan Cancer Hospital from August 2018 to December 2020. They were divided into drug group, focused ultrasound group and fractional CO2 laser group by random number table method, with 42 patients in each group. The drug group was treated with mometasone furoate cream or dexamethasone acetate cream, and the focused ultrasound group was treated with focused ultrasound; the fractional CO2 laser group was treated with fractional CO2 laser. The serum interleukin-2 (IL-2), tumor necrosis factor-a (TNF-ot), C-reactive protein (CRP), and human epidermal growth factor (EGF) levels before and after treatment, and Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) scores of the three groups were compared. Results Before treatment, there was no significant difference in the levels of IL-2, TNF-a, CRP and EGF among the three groups (all P > 0. 05). After treatment, the levels of IL-2, TNF-ct, CRP and EGF in the three groups were significantly decreased, and the levels of IL-2, TNF-ct, CRP and EGF in the focused ultrasound group and fractional CO2 laser group were lower than those in the drug group,with statistically significant difference (all P <0. 05). Before treatment, there was no significant difference in the white lesions, dry pruritus, sexual pain and chapped skin scores of the three groups (all P > 0. 05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO2 laser were lower than those of the drug group, with statistical significance (all P < 0. 05). Before treatment, there was no significant difference in the scores of symptoms and feelings, daily activities and interpersonal relationship of the three groups (all P > 0. 05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO2 laser were lower than those of the drug group, with statistical significance (all P < 0. 05). Conclusions Fractional CO2 laser has a remarkable effect in the treatment of gynecological vulva white lesions, which can reduce the level of inflammatory factors in patients, improve the pain condition, and improve the quality of life.Copyright © 2023 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Pujade-Lauraine, E., et al. (2023). "Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial." JCO precision oncology 7: e2200258.
	Purpose: The PAOLA-1/ENGOT-ov25 trial of maintenance olaparib plus bevacizumab for newly diagnosed advanced high-grade ovarian cancer demonstrated a significant progression-free survival (PFS) benefit over placebo plus bevacizumab, particularly in patients with homologous recombination deficiency (HRD)-positive tumors. We explored whether mutations in non- BRCA1 or BRCA2 homologous recombination repair (non-BRCA HRRm) genes predicted benefit from olaparib plus bevacizumab in PAOLA-1.; Methods: Eight hundred and six patients were randomly assigned (2:1). Tumors were analyzed using the Myriad MyChoice HRD Plus assay to assess non-BRCA HRRm and HRD status; HRD was based on a genomic instability score (GIS) of ≥ 42. In this exploratory analysis, PFS was assessed in patients harboring deleterious mutations using six non-BRCA HRR gene panels, three devised for this analysis and three previously published.; Results: The non-BRCA HRRm prevalence ranged from 30 of 806 (3.7%) to 79 of 806 (9.8%) depending on the gene panel used, whereas 152 of 806 (18.9%) had non- BRCA1 or BRCA2 mutation HRD-positive tumors. The majority of tumors harboring non-BRCA HRRm had a low median GIS; however, a GIS of > 42 was observed for tumors with mutations in five HRR genes ( BLM , BRIP1 , RAD51C , PALB2 , and RAD51D ). Rates of gene-specific biallelic loss were variable (0% to 100%) in non-BRCA HRRm tumors relative to BRCA1 -mutated (99%) or BRCA2 -mutated (86%) tumors. Across all gene panels tested, hazard ratios for PFS (95% CI) ranged from 0.92 (0.51 to 1.73) to 1.83 (0.76 to 5.43).; Conclusion: Acknowledging limitations of small subgroup sizes, non-BRCA HRRm gene panels were not predictive of PFS benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in PAOLA-1, irrespective of the gene panel tested. Current gene panels exploring HRRm should not be considered a substitute for HRD determined by BRCA mutation status and genomic instability testing in first-line high-grade ovarian cancer.

Pundir, J., et al. (2021). "Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis." Human Reproduction Update 27(3): 474-485.
	Background: The aromatase inhibitor letrozole is increasingly recommended for ovulation induction, as it is more effective with fewer side-effects than other agents. But many clinicians are reluctant to use the drug for fertility treatment due to a strong-label warning against its use, which warns about congenital malformation risk to the foetus in women seeking pregnancy.; Objective and Rationale: The aim of this study was to determine the risks of congenital malformations and pregnancy loss with letrozole compared with clomiphene primarily, and with other fertility drugs and natural conception.; Search Methods: A systematic review and meta-analysis using PRISMA harms guidelines. We searched MEDLINE, EMBASE and other sources from inception until January 2020, with the MeSH words for 'letrozole' and pregnancy OR foetal/neonatal outcome. We included studies reported on congenital malformations in foetuses born to mothers conceived after fertility treatment, with letrozole versus clomiphene, placebo, gonadotrophins, metformin, natural conception or other agents, from randomised trials, comparative cohort studies and non-comparative observational cohorts. Quality of the studies was assessed using Cochrane risk of bias tool and Newcastle Ottawa Scale. The McMaster tool was used to assess the quality of reported harm for foetal congenital malformations in the studies. We compared the absolute risk of events using risk difference measures and pooled the findings using a fixed-effect model. We evaluated the statistical heterogeneity using forest plots and the I2 statistic and funnel plot to assess publication bias. We assessed the strength of evidence for congenital malformation and pregnancy loss as per the GRADE recommendations and with the Fragility index.; Outcomes: We included 46 studies (18 randomised trials; 21 comparative cohorts; 7 non-comparative cohorts). Overall 2.15% (101/4697; 95% CI 1.7 to 2.5) of babies conceived on letrozole for fertility treatment had congenital foetal malformations. We did not observe a significant increase in congenital malformations with letrozole versus clomiphene in the randomised trials (risk difference (RD) 0.01, 95% CI -0.02, 0.03; I2 = 0%; 14 studies) and found a significant reduction in the cohort studies (RD -0.02, 95% CI -0.04, -0.01; I2 = 0%, 11 studies). The fragility index was 44% (7/16) (either an increase in the intervention arm or a decrease in control arm was needed to alter the results). The risks of pregnancy loss were not increased with letrozole versus clomiphene in the 14 randomised trials (RD -0.01, 95% CI -0.06, 0.04; I2 = 0%), and the risks were reduced in the six cohort studies (RD -0.09, 95% CI -0.17, -0.00; I2 = 68%). The GRADE quality of evidence was low to moderate for congenital malformations and pregnancy loss. We did not find any increased congenital malformation risk with letrozole versus gonadotrophins, natural conception or natural cycle ART, but the number of studies was small.; Wider Implications: There is no evidence that letrozole increases the risk of congenital foetal malformation or pregnancy loss compared with clomiphene, natural conception or other fertility agents, to warrant warning against its use. Given its therapeutic benefits and lack of evidence of harm to the foetus, clinicians should consider letrozole as first-line agent for ovulation induction. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purwar, R., et al. (2022). "Lymphadenectomy in ovarian cancers: a meta-analysis of hazard ratios from randomized clinical trials." World Journal of Surgical Oncology 20(1): 367.
	Background: The debate surrounding systematic lymphadenectomy in the epithelial cancers of the ovary (EOC) was temporarily put to rest by the LION trial. However, there was a glaring disparity between the number of patients registered and the number of patients randomized suggesting inadvertent selection. A subsequent meta-analysis after this trial included all types of studies in the literature (randomized, non-randomized, case series, and, retrospective cohort), thus diluting the results.; Methods: We conducted a meta-analysis of hazard ratios of randomized controlled trials, to study the role of systematic para-aortic and pelvic lymph node dissection in the EOC. A detailed search of MEDLINE, Cochrane, and Embase databases was done to look for the published randomized controlled trials (RCT) comparing lymphadenectomy versus no lymphadenectomy in EOC. A meta-analysis of hazard ratios (HR) was performed for overall survival (OS) and progression-free survival (PFS) using fixed and random effect models. The quality of the RCTs was evaluated on Jadad's score, and the risk of bias was estimated by the Cochrane tool.; Results: A total of 1342 patients with EOC were included for quantitative analysis. On meta-analysis, HR for PFS was 0.9 (95% CI 0.79-1.04) favoring lymphadenectomy. HR for OS was 1 (95% CI 0.84-1.18) signifying no benefit of systematic lymphadenectomy.; Conclusion: The results show a trend towards increased PFS which did not reach statistical significance nor translate into any meaningful benefit in OS. There is still a need for a greater number of well-conducted, suitably powered trials to convincingly answer this question. (© 2022. The Author(s).)

Pushpam, P. and Seema (2023). "Letrozole versus Clomiphene Citrate for Ovulation Induction in Anovulatory Infertility: A comparative study." International Journal of Pharmaceutical and Clinical Research 15(5): 2086-2092.
	Background: The multifaceted health issue of infertility has negative societal and economic effects. Ovulatory abnormalities are the most prevalent recognisable female factor, and female factors still account for 40% to 55% of all causes. One of the most effective treatments for infertility brought on by anovulation is ovulation induction. The study's objective was to contrast the results of ovulation induction with letrozole and clomiphene citrate (CC) in females with anovulatory infertility. Method(s): 40 infertile women with anovulatory infertility were randomised to receive either letrozole or CC for ovulation induction at incremental doses for a maximum of three cycles in this assessor-blinded randomised controlled experiment. Endometrial thickness, ovulation frequency, pregnancy frequency, and rate of mono-follicular formation were the main outcomes examined. Both groups received 10,000 IU of human chorionic gonadotropin (hCG), timing of sexual activity was suggested, and ultrasound monitoring continued until the dominant follicle achieved a diameter of less than 18 mm. Result(s): In both groups, the mean age, length of infertility, BMI, and endocrine status were comparable at the outset. In the letrozole group, 18 participants (90.0%) and in the CC group, 14 subjects (70.0%) experienced ovulation; this difference was statistically significant (P=0.0471). In the letrozole group, mono-follicular development was observed in 12 (60.0%) of ovulatory cycles as opposed to 5 (25.0%) in the clomiphene group (p=0.001). In the letrozole group, seven women (35%) and in the clomiphene group, five women (25%) both became pregnant (p=0.230). When hCG was administered, there was no statistically significant difference in the thickness of the endometrium between the two groups (9.69+/-1.22 mm vs. 9.80+/-1.05 mm with letrozole and clomiphene, respectively; p = 0.650). Conclusion(s): In comparison to CC, letrozole impact demonstrated a higher ovulation rate and mono follicular development. Patients with anovulatory infertility may benefit from letrozole as a first-line treatment.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Pyrzak, A., et al. (2023). "Effect of Centering Preoperative Counseling on Patient-Reported Anxiety in Patients with Gynecologic Malignancies." Journal of Gynecologic Surgery 39(2): 74-81.
	Objectives: Centering is a unique form of counseling that unifies education and supporting patients with similar conditions to facilitate learning and develop a mutual support network. This study's primary objective was to evaluate the effect of centering preoperative counseling on anxiety scores in patients with newly diagnosed gynecologic malignancies. Secondary outcomes included the effect of this form of counseling on depression, compliance with preoperative instructions, hospital length of stay, and use of unscheduled health care resources. Material(s) and Method(s): In this prospective cohort study, women with known or suspected gynecologic malignancies were assigned to standard-of-care counseling or centering. The centering cohort participated in a 1-1.5 hour online group-counseling session before surgery. All participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression patient-reported outcome (PRO) surveys at baseline, preoperatively, and 4 weeks postoperatively. Paired and unpaired t-tests were used to evaluate differences in PROs between timepoints and between the cohorts. chi2, Fisher's exact, and Wilcoxon rank-sum tests were used to evaluate secondary outcomes. Result(s): There were 17 patients in the standard-of-care cohort and 52 patients in the intervention cohort evaluated. The centering group had a reduction of 4.8 points in anxiety scores after the intervention. There was no difference in Enhanced Recovery After Surgery compliance or utilization of unscheduled health care resources between the 2 cohorts. Conclusion(s): Centering preoperative counseling meaningfully reduces anxiety scores in patients undergoing surgery for suspected gynecologic malignancy. (J GYNECOL SURG 39:74)© Copyright 2023, Mary Ann Liebert, Inc., publishers 2023.

Qayyum, S., et al. (2023). "Therapeutic Efficacy of a Formulation Prepared with Linum usitatissimum L., Plantago ovata Forssk., and Honey on Uncomplicated Pelvic Inflammatory Disease Analyzed with Machine Learning Techniques." Pharmaceutics 15(2).
	A single-blind double-dummy randomized study was conducted in diagnosed patients (n = 66) to compare the efficacy of Linseeds ( Linum usitatissimum L.), Psyllium ( Plantago ovata Forssk.), and honey in uncomplicated pelvic inflammatory disease (uPID) with standard drugs using experimental and computational analysis. The pessary group received placebo capsules orally twice daily plus a per vaginum cotton pessary of powder from linseeds and psyllium seeds, each weighing 3 gm, with honey (5 mL) at bedtime. The standard group received 100 mg of doxycycline twice daily and 400 mg of metronidazole TID orally plus a placebo cotton pessary per vaginum at bedtime for 14 days. The primary outcomes were clinical features of uPID (vaginal discharge, lower abdominal pain (LAP), low backache (LBA), and pelvic tenderness. The secondary outcomes included leucocytes (WBCs) in vaginal discharge on saline microscopy and the SF-12 health questionnaire. In addition, we also classified both (pessary and standard) groups using machine learning models such as Decision Tree (DT), Random Forest (RF), Logistic Regression (LR), and AdaBoost (AB). The pessary group showed a higher percentage reduction than the standard group in abnormal vaginal discharge (87.05% vs. 77.94%), Visual Analogue Scale (VAS)-LAP (80.57% vs. 77.09%), VAS-LBA (74.19% vs. 68.54%), McCormack pain scale (McPS) score for pelvic tenderness (75.39% vs. 67.81%), WBC count of vaginal discharge (87.09% vs. 83.41%) and improvement in SF-12 HRQoL score (94.25% vs. 86.81%). Additionally, our DT 5-fold model achieved the maximum accuracy (61.80%) in the classification. We propose that the pessary group is cost-effective, safer, and more effective as standard drugs for treating uPID and improving the HRQoL of women. Aucubin, Plantamajoside, Herbacetin, secoisolariciresinol diglucoside, Secoisolariciresinol Monoglucoside, and other various natural bioactive molecules of psyllium and linseeds have beneficial effects as they possess anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory properties. The anticipated research work is be a better alternative treatment for genital infections.

Qi, G. (2021). "Analysis of the application effect of misoprostol combined with lidocaine in artificial abortion." 中国实用医药 16(17): 146‐149.
	Objective: To investigate the application effect of misoprostol combined with lidocaine in artificial abortion. METHODS: 80 patients with induced abortion were randomly divided into a combined medication group and a blank untreated group, 40 cases in each. The patients in the blank untreated group underwent artificial abortion directly, while in the combined medication group, misoprostol was placed in the vagina before operation, and lidocaine was given during the operation. The intraoperative pain, induced abortion time, total blood loss and adverse reactions were compared between the two groups. RESULTS: The pain complaint rate in the combined medication group was 20.0%, which was significantly lower than that in the blank untreated group, which was 87.5%, and the difference was statistically significant (P<0.05). The artificial abortion time of the combined medication group was (3.25±1.72) min shorter than that of the blank untreated group (5.92±3.28) min, the total blood loss in the whole process was (45.72±5.93) ml, and the incidence of adverse reactions was 5.0% lower than that of the blank untreated group. The difference of (75.83±7.64)ml and 22.5% in the treatment group was statistically significant (P<0.05). Conclusion: The combination of misoprostol and lidocaine in induced abortion can significantly relieve the pain of patients and shorten the time of induced abortion, which is worthy of clinical promotion.

Qi, J., et al. (2021). "Evaluation of safety and efficacy of apatinib combination with chemotherapy for ovarian cancer treatment: a systematic review and meta-analysis." Annals of Palliative Medicine 10(9): 9902-9913.
	Background: Apatinib in combination with chemotherapy (CT) has been used in the treatment of ovarian cancer (OC), however, the safety and efficacy are unclear. The study aims at systematic evaluation of the safety and efficacy of the apatinib targeted therapy in combination with CT for the treatment of patients with advanced OC.; Methods: Literature about randomized controlled clinical trials was searched using search engines such as PubMed, EMBASE, Web of Science, CNKI, the Cochrane Library, CBM, VIP and the Wanfang. We collected the related clinical studies of apatinib in combination with CT in the treatment of OC. The duration of the data retrieval related to clinical studies was from the database establishment to September 2020. Adverse reactions (ADRs) due to treatment, disease control rate (DCR), and that of objective response rate (ORR), were collected as indicators to show treatment outcomes. The literature was independently screened by two researchers. They extracted the data and evaluated the risk of biases of the included studies. Then, Revman 5.4 software was employed for performing the meta-analysis.; Results: Twelve randomized controlled clinical trials with 698 patients having an advanced stage of OC were included. The results revealed that in comparison with the treatment with only CT, apatinib targeted therapy combination with CT showed significant improvement in the patients' ORR [OR =3.19, 95% CI: (2.06, 4.94), P<0.00001] and DCR [OR =4.97, 95% CI: (2.90, 8.52), P<0.00001]. The group that was treated with a combined therapy had shown proteinuria in higher amount (OR =3.08, 95% CI: 51.13-8.42, P<0.00001), while the analyses of other ADRs, such nausea and vomiting (OR =1.10, 95% CI: 0.67-1.79, P=0.71), hand-foot syndrome (OR =1.73, 95% CI: 0.97-3.10, P=0.06), hypertension (OR =1.18, 95% CI: 0.73-1.91, P=0.0.51), diarrhea (OR =1.05, 95% CI: 0.56-1.97, P=0.87), leucopenia (OR =1.22, 95% CI: 0.70-2.12, P=0.48), and myelosuppression (OR =1.00, 95% CI: 0.28-3.62, P=1.00), did not show any significant difference (P>0.05).; Discussion: The effects of apatinib combination with CT for the treatment of OC are significantly better than the CT used alone in ORR and DCR, despite with a relative low incidence of adverse effects. However, due to the very low number of studies available, the results need to be further verified using a high-quality, large sample and long-term studies.

Qi, L., et al. (2022). "Efficacy and safety of pembrolizumab on cervical cancer: A systematic review and single-arm meta-analysis." Frontiers in Oncology 12: 910486.
	Background: According to current research, the objective response rate and overall survival of pembrolizumab in the treatment of several types of solid tumors have been significantly improved. Some high-quality clinical trials have studied the effect of applying pembrolizumab in treating cervical cancer. Multiple clinical trials have been conducted, and some of them have shown good results as expected. Therefore, we performed this meta-analysis on existing studies to reveal the efficacy and safety of pembrolizumab in treating cervical cancer.; Methods: PubMed, Embase, Cochrane Library and Web of Science were searched for literatures published until October 31, 2021. Outcomes included complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), the best time to response (TTR), death rate, adverse events (AE).; Results: A total of 7 studies with 727 patients were included. The results were as follows: CR (0.027, 95%CI: 0.008-0.053), PR (0.104, 95% CI: 0.074-0.145), SD (0.190, 95% CI: 0.149-0.240), PD (0.541, 95% CI: 0.421-0.661). ORR was 0.155 (95% CI: 0.098-0.236) and DCR was 0.331 (95% CI: 0.277-0.385). OS was 10.23 months (95% CI: 8.96-11.50) and PFS was 4.27 months (95% CI: 1.57-6.96). TTR was 2.10 months (95%CI: 1.69-2.51). The 1-year death rate was 0.388 (95% CI: 0.230-0.574). Main adverse events included abnormal liver function, hypothyroidism, neutropenia, anemia, decreased appetite, fatigue, fever, etc. The total incidence of the adverse events of grade 3 and above was 0.212 (95% CI: 0.065-0.509).; Conclusions: Pembrolizumab provides significant benefits in response rate and survival for cervical cancer patients. The results from recent high-quality clinical trials are expected to validate these findings.; Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021291723.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Qi, Li, Lin, Wang and Cong.)

Qi, T., et al. (2021). "Effect of Motherwort Tablets in the Repair of Uterus and Changes in Hormone Levels after Artificial Abortion in Early Pregnancy." 世界中医药 16(19): 2922‐2926.
	Objective: To explore the effect of Motherwort on uterine repair and hormone level changes after artificial abortion in early pregnancy. Methods: From January 2016 to October 2020, 106 patients with artificial abortion after early pregnancy who were admitted to Lianyungang First People's Hospital were selected as the research objects, and divided into the control group and the observation group according to the random number table method, with 53 cases in each group. All patients underwent routine induced abortion. The control group was given drospirenone and ethinylestradiol tablets + Bazhen granules after operation. The observation group was given motherwort dispersible tablets on the basis of the control group. The symptom relief time, sex hormone level, vaginal bleeding volume score, pain score and incidence of adverse reactions were compared between the two groups. Results: The vaginal bleeding time, abdominal pain relief time, menstrual cycle recovery time and endometrial recovery time in the observation group were all shorter than those in the control group (P<0.05). Conclusion: For patients undergoing artificial abortion in early pregnancy, the combined use of Motherwort on the basis of routine medication can effectively inhibit postoperative bleeding, strengthen uterine contractions, help improve postoperative sex hormones and relieve pain, with good safety.

Qi, Y., et al. (2022). "Intracavitary physiotherapy combined with acupuncture mediated AMPK/mTOR signalling to improve endometrial receptivity in patients with thin endometrium." European Journal of Obstetrics, Gynecology, and Reproductive Biology 277: 32-41.
	Objective: To explore the mechanism of intracavitary physiotherapy combined with acupuncture to improve the receptivity of thin endometrium.; Methods: From October 2020 to April 2021, 40 patients diagnosed with thin endometrium and preparing for hormone replacement cycle freeze-thaw embryo transfer in our centre for Reproduction were included, 40 patients were randomized to treatment group and control group. 20 patients with normal endometrium during the same period were selected as the normal group.All patients underwent freeze-thaw embryo transfer using hormone replacement cycles.The treatment group added endovascular physiotherapy combined with acupuncture.; Results: The endometrial receptivity of the patients with thin endometrium was significantly lower than that of the normal group(P < 0.01). Endovascular therapy combined with acupuncture can significantly increase endometrial thickness in patients with thin endometrium and the proportion of patients with type A endometrium, reduce bilateral Uterine arterial pulsatilityindex (PI), Uterine arterial resistance index (RI), and peaksystolicvelocity/diastolicvelocity (S/D), upregulate the expression of HOXA10 protein and mRNA in endometrium tissue, and improve the rate of embryo implantation and clinical pregnancy(P < 0.01).there was no significant difference between the treatment group and the normal group (P > 0.05). This may be related to the regulation of the AMPK/mTOR signalling pathway by intracavitary physiotherapy combined with acupuncture, downregulation of the expression of the AMPK gene and protein and upregulation of the expression of the mTOR gene and protein.; Conclusions: 1. Abnormal energy metabolism is present in the endometrium of patients with thin endometrium, which affects the autophagy process and leads to a decrease in the receptivity of thin endometrium. 2. Intracavitary physiotherapy combined with acupuncture mediated the AMPK/mTOR pathway to improve energy metabolism, promote the autophagy process, improve endometrial morphology and ultrasonic indicators of patients, upregulate the expression of endometrial receptivity-related HOXA10 genes and proteins, and improve the embryo implantation rate and clinical pregnancy rate.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Qi, Y., et al. (2022). "Cytoreductive Surgery (CRS) Combined With Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Platinum-Sensitive Recurrence Epithelial Ovarian Cancer With HRR Mutation: A Phase III Randomized Clinical Trial." Technology in cancer research & treatment 21: 15330338221104565.
	Background : Epithelial ovarian cancer (EOC) remains the leading cause of gynecologic cancer death worldwide due to the high recurrence rate. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality for platinum-sensitive recurrent EOC. The latest studies demonstrate homologous recombination-related (HRR) mutation status increases the sensitivity to platinum-based chemotherapy drugs in EOC. However, the molecular analysis of recurrent EOC patient benefits from HIPEC is unknown. Thus, we aimed to evaluate the efficacy and safety of CRS combined with HIPEC for platinum-sensitive in recurrent EOC with HRR mutation. Methods: This is a phase III randomized controlled clinical trial in patients with platinum-sensitive recurrent EOC. Participants were divided into 2 groups based on the HRR mutation status and randomized to receive CRS + HIPEC. The patients then received periodic chemotherapy and follow-up. Results: The primary objective of this study was to evaluate the effect of CRS + HIPEC compared to CRS alone in patients with a platinum-sensitive recurrent EOC stratified for HRD status. We hypothesize that the addition of HIPEC to CRS improves the progression-free survival (PFS) of platinum-sensitive recurrent EOC patients with HRR mutation compared with patients without HRR mutation. Conclusion: Recurrent EOC has a poor prognosis due to implantation and metastasis in the abdominal cavity. Intraperitoneal chemotherapy reduced seeding by removing free tumor cells. HIPEC utilizes physical and biological properties to significantly increase the clearance rate of tumors. Van Driel WJ et al proposed that HIPEC using platinum-based chemotherapy improves the survival of patients with ovarian cancer. HRR mutation, as a common pathogenic mutation in ovarian cancer, has a predictive effect on the platinum sensitivity of ovarian cancer patients. Whether lobaplatin-based HIPEC will play a greater role in ovarian cancer patients with HRR mutations is currently unknown.

Qian, J., et al. (2024). "Primary vaginal cancer after hysterectomy for benign conditions: a systematic review of the literature." Frontiers in Oncology 14: 1334778.
	BACKGROUND: Primary vaginal cancer is a rare condition. Some studies have revealed an increased risk of vaginal cancer among patients who have undergone hysterectomy for premalignant and malignant cervical disease. However, there is limited literature available on primary vaginal cancer following hysterectomy for benign conditions. OBJECTIVES: This review aimed to investigate available evidence on clinical characteristics, treatments, and outcomes of primary vaginal cancer following hysterectomy for benign diseases. Additionally, we provide a case of a patient who developed primary vaginal cancer 10 years after undergoing hysterectomy for abnormal uterine bleeding. SEARCH STRATEGY: We conducted a comprehensive literature search on PubMed, Scopus, Web of Science using a combination of title and abstract represented by "hysterectomy", and "vaginal cancer"; "vaginal neoplasm"; and "cancer of vagina". No article type restrictions were applied. MAIN RESULTS: Eight studies with a total of 56 cases were included in this review. The main symptom observed was vaginal bleeding. Squamous cancer was found to be the most common type, followed by adenocarcinoma. The majority of vaginal cancer cases occurred approximately 10 years after undergoing hysterectomy. The most common location of the tumor was in the vaginal apex. The management approaches varied and details were available in 25 cases. Among these, 7 cases were treated with radiotherapy alone, 1 case received concurrent chemoradiation therapy, and the of rest of the cases underwent surgery as the primary treatment, with or without additional adjuvant therapy. Data of follow-up was available for 15 cases, with 2 cases resulting in death and 2 cases experiencing recurrence. The other cases were alive and well at the time of considered follow up. CONCLUSION: Primary vaginal cancer after hysterectomy for benign conditions is an extremely rare condition. It is essential to have high-level evidence to guide the screening and treatment strategy for this rare condition. A part of women who have undergone hysterectomy for benign disorders can benefit from vaginal cytology evaluation. It is reasonable to postpone the initial screening after surgery and to extend the interval between subsequent screenings. Further retrospective case-control trials are expected to determine which specific subgroups of patients mentioned above might most potentially benefit from screening. The treatment decision for vaginal cancer after hysterectomy is more favorable to radiotherapy-based management rather than surgery. Vaginal endometrioid adenocarcinoma may arise from the malignant transformation of endometriosis. More studies are expected to investigate the correlation between these two diseases.

Qian, J., et al. (2023). "Art-based interventions for women's mental health in pregnancy and postpartum: A meta-analysis of randomised controlled trials." Frontiers in Psychiatry 14: 1112951.
	Objective: Pregnant and postpartum women are vulnerable to psychological problems with a high estimated prevalence. To date, there is no meta-analysis that specifically assesses the effectiveness of art-based interventions to improve mental health in pregnant and postpartum women. The objective of this meta-analysis was to assess the efficacy of art-based interventions when delivered to pregnant and postpartum women. Method(s): Systematic literature searches were conducted from the inception to 6 March 2022 in seven English databases, including PubMed, Embase, Cochrane Central Register, CINAHL, ProQuest, Scopus, and Web of Science. Randomised controlled trials (RCTs) reporting art-based interventions targeting the improvement of women's mental health in pregnancy and postpartum were included. Cochrane risk of bias tool was applied to assess evidence quality. Result(s): Twenty-one randomised controlled trials (RCTs) involving 2,815 participants were eligible for data analysis. A pooled analysis demonstrated that art-based interventions significantly reduced anxiety (SMD = -0.75, 95% CI = -1.10 to -0.40) and depression symptoms (MD = -0.79, 95% CI = -1.30 to -0.28). However, art-based interventions did not alleviate stress symptoms as expected in our findings. Subgroup analysis demonstrated that intervention implementation time, intervention duration and music selected by the participants vs. not could have influence on the efficacy of art-based intervention for anxiety. Conclusion(s): In perinatal mental health, art-based interventions may be effective in alleviating anxiety and depression. In the future, we still need to conduct high-quality RCTs to validate our findings and enrich clinical application of art-based interventions.Copyright © 2023 Qian, Sun, Wang, Sun and Yu.

Qian, L., et al. (2023). "Mass Spectrometry-Based Proteomics of Epithelial Ovarian Cancers: A Clinical Perspective." Molecular & cellular proteomics : MCP 22(7): 100578.
	Increasing proteomic studies focused on epithelial ovarian cancer (EOC) have attempted to identify early disease biomarkers, establish molecular stratification, and discover novel druggable targets. Here we review these recent studies from a clinical perspective. Multiple blood proteins have been used clinically as diagnostic markers. The ROMA test integrates CA125 and HE4, while the OVA1 and OVA2 tests analyze multiple proteins identified by proteomics. Targeted proteomics has been widely used to identify and validate potential diagnostic biomarkers in EOCs, but none has yet been approved for clinical adoption. Discovery of proteomic characterization of bulk EOC tissue specimens has uncovered a large number of dysregulated proteins, proposed new stratification schemes, and revealed novel targets of therapeutic potential. A major hurdle facing clinical translation of these stratification schemes based on bulk proteomic profiling is intra-tumor heterogeneity, namely that single tumor specimens may harbor molecular features of multiple subtypes. We reviewed over 2500 interventional clinical trials of ovarian cancers since 1990 and cataloged 22 types of interventions adopted in these trials. Among 1418 clinical trials which have been completed or are not recruiting new patients, about 50% investigated chemotherapies. Thirty-seven clinical trials are at phase 3 or 4, of which 12 focus on PARP, 10 on VEGFR, 9 on conventional anti-cancer agents, and the remaining on sex hormones, MEK1/2, PD-L1, ERBB, and FRα. Although none of the foregoing therapeutic targets were discovered by proteomics, newer targets discovered by proteomics, including HSP90 and cancer/testis antigens, are being tested also in clinical trials. To accelerate the translation of proteomic findings to clinical practice, future studies need to be designed and executed to the stringent standards of practice-changing clinical trials. We anticipate that the rapidly evolving technology of spatial and single-cell proteomics will deconvolute the intra-tumor heterogeneity of EOCs, further facilitating their precise stratification and superior treatment outcomes.; Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T. G. is the founder of Westlake Omics Inc. The other authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Qianhui, Y. and L. Tie (2022). "Auricular therapy for primary dysmenorrhea : a protocol for systematic review and meta-analysis of randomized controlled trials." PROSPERO International prospective register of systematic reviews.
	
Qianmei, Y., et al. (2021). "Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy." Immunologic Research 69(5): 398-414.
	Th17 and Treg cells play an important role in regulating tissue inflammation and maintaining the stability of the immune system. They regulate inflammatory responses, participate in the occurrence and development of autoimmune diseases and tumors, and determine the disease progress. Malignant tumor is one of the diseases with the highest mortality rate in the world. However, the efficacy of traditional treatment is limited, so it is necessary to find safe and efficient treatment methods. Studies have shown that the balance of Th17/Treg cells plays a critical role in tumor progression. In this paper, we review the antitumor and tumor-suppressing effects of Th17/Treg cells, and new strategies for tumor therapy, combined with new research hotspots such as immune checkpoint therapy, miRNA-related gene therapy, and metabolic pathway regulation of Th17/Treg cell differentiation and tumor generation. The synergistic therapy is expected to be widely used in the future clinical practice, providing a new choice for the prevention and treatment of malignant tumors.Copyright © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

qianting, w. and L. ErNiao (2023). "Effect of omega-3 Polyunsaturated fatty acid on Endometriosis."
	
Qiao, Y., et al. (2022). "Neoadjuvant and Adjuvant Treatments Compared to Concurrent Chemoradiotherapy for Patients With Locally Advanced Cervical Cancer: A Bayesian Network Meta-Analysis." Frontiers in Oncology 12: 745522.
	Aim: This study aimed to identify the most effective treatment mode for locally advanced cervical cancer (LACC) by adopting a network meta-analysis (NMA).; Methods: Randomized controlled trials about treatments were retrieved from PubMed, Medline and Embase. Odds ratios (OR) of overall survival (OS) and progression-free survival (PFS) were calculated by synthesizing direct and indirect evidence to rank the efficacy of nine treatments. Consistency was assessed by node-splitting method. Begg's test was performed to evaluate publication bias. The surface under cumulative ranking curve (SUCRA) was also used in this NMA.; Results: A total of 24 eligible randomized controlled trials with 6,636 patients were included in our NMA. These trials compared a total of nine different regimens: radiotherapy (RT) alone, surgery, RT plus adjuvant chemotherapy (CT), concurrent chemoradiotherapy (CCRT), neoadjuvant CT plus CCRT, CCRT plus adjuvant CT, neoadjuvant CT, RT, CCRT plus surgery. Among those therapeutic modalities, we found that the two interventions with the highest SUCRA for OS and PFS were CCRT and CCRT plus adjuvant CT, respectively. ORs and 95% confidence interval (CI) for the two best strategies were CCRT versus CCRT plus adjuvant CT (OR, 0.84; 95% CI, 0.53-1.31) for OS, CCRT plus adjuvant CT versus CCRT (OR, 0.60; 95% CI, 0.38-0.96) for PFS.; Conclusions: This NMA supported that CCRT and CCRT plus adjuvant CT are likely to be the most optimal treatments in terms of both OS and PFS for LACC. Future studies should focus on comparing CCRT and CCRT plus adjuvant CT in the treatment of LACC.; Systematic Review Registration: PROSPERO, CRD42019147920.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Qiao, Li and Peng.)

Qiaoli, Z. and Y. Xiaokui (2022). "Effects of intrauterine perfusion of autologous platelet-rich plasma on recurrent implantation failure in frozen-thawed embryo transfer: a meta-analysis of randomized controlled trials." PROSPERO International prospective register of systematic reviews.
	
Qiaoqiao, L. and Z. Liu (2022). "Systematic review and meta-analysis of Pure moxibustion in the treatment of primary dysmenorrhea."
	
Qihong, S., et al. (2021). "The efficacy of Shenghua Decoction supplementation after early medical abortion: a meta-analysis of randomized controlled trials." PROSPERO International prospective register of systematic reviews.
	
Qiling, S., et al. (2021). "A meta-analysis of combination between mifepristone and methotrexate to treat ectopic pregnancy." PROSPERO International prospective register of systematic reviews.
	
Qin, Q., et al. (2021). "Intrauterine administration of peripheral blood mononuclear cells activated by human chorionic gonadotropin in patients with repeated implantation failure: A meta-analysis." Journal of Reproductive Immunology 145: 103323.
	The purpose of this study was to assess whether intrauterine administration of peripheral blood mononuclear cells (PBMCs) activated by human chorionic gonadotropin (hCG) could improve the pregnancy and live birth rates in women with repeated implantation failure (RIF), and whether the parameters of co-culture of hCG and PBMCs would affect the clinical outcomes. Six databases (PubMed, Ovid, Medline, NCBI, Cqvip and Wanfang) were searched up to October 2020 by two independent reviewers. Seven studies were included according to specific inclusion and exclusion criteria. A meta-analysis showed that the pregnancy and live birth rates were significantly increased in the case group compared with the control group (odds ratio [OR]: 3.43, 95 % confidence interval [CI]: 1.78-6.61; P = 0.0002 and OR: 2.79, 95 % CI: 1.09-7.15; P = 0.03), especially when hCG was cultured with PBMCs for 48 h or PBMCs administration was performed two or three days before embryo transfer (ET). Neither the dosage of the hCG co-cultured with PBMCs nor the mean concentration of the administered PBMCs appeared to influence the therapeutic efficiency. In conclusion, intrauterine administration of PBMCs co-cultured with hCG for 48 h, conducted two or three days before ET, could be an effective therapy for women experiencing RIF. Due to the limitations of sample size and quality of the included studies, further high-quality studies with large sample sizes are warranted to optimize the parameters of hCG and PBMC co-culture to help more RIF patients benefit from this therapy. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Qin, X., et al. (2021). "A comparison of the efficacy and safety of traditional Chinese medicine in preconditioning patients with diminished ovarian reserve that would undergo In Vitro fertilization: A network meta-analysis protocol." Medicine 100(4): e24408.
	Background: Diminished Ovarian Reserve (DOR) is a common disease in reproductive-age women in the diagnosis and treatment of infertility. The incidence of DOR increased quickly in recent years and had became one of the most important factors that made the quality of women life decline. Gynecology and reproductive medicine professors have made great efforts to explore good treatment methods all over the world. Traditional Chinese Medicine has made some achievement in treating DOR as a kind of complementary and alternative therapy In Vitro Fertilization (IVF) in recent years, it is indispensable to propose a network meta-analysis (NMA) protocol to discuss the efficacy and safety of TCM in IVF.; Methods: A literature search will be conducted in 8 electronic databases.; Results: The efficacy and safety of traditional Chinese medicine in preconditioning patients with diminished ovarian reserve that would undergo In Vitro Fertilization will be evaluated.; Results: The systematic review will evaluate the efficacy and safety of TCM in IVF.; Conclusion: The result of this study will provide reliable evidence of the use of TCM in IVF.; Inplasy Registration Number: INPLASY2020110062.; Ethics and Dissemination: This review does not require ethical approval.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Qin, X., et al. (2023). "Impact of heamostasis methods during ovarian cystectomy on ovarian reserve: A pairwise and network meta-analysis."
	Review question Patients: patients with ovarian cystectomy I/C: three hemostasis methods (bipolar energy, suture, the FloSeal) O: ovarian reserve(the level of anti-Müllerian hormone ) Searches Sources: the Cochrane Library, PubMed, and Web of Science Types of study to be included RCT Condition or domain being studied The ovarian cyst is a common gynecological presentation seen in approximately 6.6% of reproductive-age women. It was reported that up to 10% of women would have surgery for an ovarian cyst in their lifetime, and ovarian cystectomy is more favorable among these surgical treatments. However, though the ovarian cysts are solved, women after surgical management were found with a diminished ovarian reserve and risk of premature ovarian failure, which was attached with great emphasis. Hemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three hemostasis methods (bipolar energy, suture, the FloSeal) on ovarian reserve in patients with ovarian cysts are not well known. Therefore, a pairwise and network meta-analysis was performed to evaluate the efficacy of other hemostasis in preventing fertility damage. Participants/population patients were diagnosed as an ovarian cyst with a plan to ovarian cystectomy; Intervention(s), exposure(s) One of the three hemostasis methods including suture or electrocoagulation (bipolar) or the hemostatic sealant was used; Comparator(s)/control One of the three hemostasis methods including suture or electrocoagulation (bipolar) or the hemostatic sealant was used; Main outcome(s) AMH level of one-month, three-months, six months and twelve months after the cystectomy surgery were recorded. Additional outcome(s) Not applicable Data extraction (selection and coding) study characteristics (authors and publication year), patient characteristics (inclusion criteria and exclusion criteria), hemostasis methods, sample size, AMH level of one-month, three-months, six months, and twelve months after the cystectomy surgery Risk of bias (quality) assessment Studies included in our research were RCTs; therefore, they were assessed according to the Cochrane Handbook of Systematic Reviews of Interventions. Strategy for data synthesis The traditional pairwise meta-analysis was conducted by Review Manager 5.4.1. The outcome of AMH level was a continuous variable and presented as Mean±SD. Statistical heterogeneity was assessed by the I² statistic and P value (P < 0.1 showed apparent heterogeneity). A random-effects model was used in the analysis.The net meta-analysis was conducted by STATA/MP 17.0. and GeMTC 0.14.3. Stata software was used to depict the Network graphs, and GeMTC software was used to carry out the data synthesis further. Analysis of subgroups or subsets Not applicable Contact details for further information Qin Xie 1193571742@qq.com Organisational affiliation of the review Department of Obstetrics and Gynecology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science Review team members and their organisational affiliations Dr Qin Xie. Department of Obstetrics and Gynecology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science Dr Xuezhou Yang. Department of Obstetrics and Gynecology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science Dr Xiaozhen Quan. Department of Obstetrics and Gynecology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science Dr Yue Xie. Department of Obstetrics and Gynecology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science Dr Ying Shi. Department of Obstetrics and Gynecology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science Type and method of review Network meta-analysis, Systematic review Anticipated or actual start date 26 September 2023 Anticipated completion date 25 October 2023 Funding sources/sponsors No funding Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms MeSH headings have not been applied to this record Date of registration in PROSPERO 06 October 2023 Date of first submission 26 September 2023 Stage of review at time of this submission The review has not started

Qin, Y. (2020). "Does endometrial injury improve outcomes of frozen-thawed embryo transfer cycle? A meta-analysis." Journal of Reproductive Medicine 65(7-8): 257-265.
	
Qiu, G., et al. (2019). "The significance of probiotics in preventing radiotherapy-induced diarrhea in patients with cervical cancer: A systematic review and meta-analysis." International journal of surgery (London, England) 65: 61-69.
	Aims: A systematic review and meta-analysis was designed to evaluate the efficacy and safety of probiotics for prevention of radiotherapy-induced diarrhea (RID) in patients with cervical cancer. Previous studies failed to give a comprehensive analysis of the efficacy and safety of probiotics in this point.; Methods: We searched the Cochrane Library, PubMed, EMBASE and Web of Science up to June 4, 2018. We also hand searched some studies included in previous reviews. Our primary outcome aims to compare the incidence of all Common Toxicity Criteria (CTC) grades of RID and adverse events (AEs) in both probiotics groups and placebo groups. Relative risk (RR) with its 95% confidence interval (CI) was used to compare the efficacy of probiotics in prevention of RID, and the pooled RRs were estimated using a fixed- or random-effect model; heterogeneity was assessed with Cochran's Q and Higgins I 2 test. Two reviewers assessed trial quality and extracted data independently. The analysis and bias for each of included studies were performed and assessed using Review Manager 5.2.; Results: Nine randomized, placebo-controlled studies (N = 1508 participants) were included for assessing the efficacy of probiotics. Compared with placebo groups, participants in probiotic groups experienced much lower incidence of RID with RR of 0.61 (95% CI 0.46-0.81; P = 0.0007). In addition, significant results were also observed in CTC grade ≥2 and grade ≥3 RID, with the pooled RRs of 0.52 (95% CI 0.30-0.98; P = 0.02) and 0.32 (95% CI 0.12-0.82; P = 0.02) respectively. Eight studies, included 1410 participants (726 consuming probiotics, 657 consuming placebo, 27 lost to follow-up), were used for the analysis of safety of probiotics. Of the 8 studies, 4 studies had no AEs caused by probiotics, while another 4 studies reported varying degrees of AEs during their treatment.; Conclusions: Probiotics may have a beneficial effect in prevention of RID generally, especially for Grade ≥2 or 3 diarrhea. Probiotics may be safe and rarely cause severe AEs during treatment. (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Qiu, L. B., et al. (2022). "Safety and Effect of High-intensity focused ultrasound and ablation versus surgical therapy for abdominal wall endometriosis: a systematic review and Meta-analysis." PROSPERO International prospective register of systematic reviews.
	Review question The aim of this study is going to identify the effect and safety of surgery and HIFU for patients with abdominal wall endometriosis (AWE). P:The patients who were diagnosed with AWE . I: HIFU ablation therapy C: Surgery O:effect and safety Searches The databases of Cochrane, Embase，ScienceDirect，PubMed，Web of Science，and CNKI in English and Chinese from January 2000 to July 2022 will be searched. The strategy on PubMed is (abdominal wall endometriosis) OR (AWE) OR (scar endometriosis) OR (Abdominal wall scar endometriosis) AND (HIFU) OR (focused ultrasound) OR (MRgFUS) OR (High-Intensity Focused Ultrasound Ablation) AND (surgery) OR (Surgical resection) Types of study to be included RCT, nRCT, Cohort Study Condition or domain being studied Abdominal wall endometriosis (AWE) is defined as the finding of endometrial glands and stoma in abdominal wall. AWE includes lesions that develop secondary to surgical incisions or those that arise spontaneously and has a reported incidence of 0.03–3.5% in reproductive-aged women, and the number of AWE patients has increased concomitantly.The surgical resection has a high success rate for the treatment of AWE.Some studies revealed that HIFU appears to be safe and effective in the treatment of AWE. Several studies have been performed comparing HIFU ablation with surgical resection in the management of AWE.However, there are contradictions between the results of these studies. Participants/population The patients who were diagnosed with AWE will be enrolled in our study. The inclusion criteria: (1) abdominal wall mass developing after previous uterine surgery; (2) gradually increasing mass with cyclic pain in or near the previous abdominal surgery scar that is exacerbated during menstruation; (3)detectable hypoechoic nodule in the abdominal wall on ultrasound; (4)the availability of complete clinical data. The exclusion criteria: (1) inflammation or ulceration of the skin in or near the nodule; (2)suspected or confirmed malignancy; (3) patients with other systemic diseases. Intervention(s), exposure(s) High-intensity focused ultrasound (HIFU) ablation, as a non-invasive treatment, is applied in treating AWE recent years. HIFU is based on the ability to concentrate a high-intensity ultrasound beam into a specific target inside the body precisely. The absorption of acoustic energy and its conversion to heat energy induce coagulative necrosis at targeted lesion in a well-circumscribed area. For the HIFU group, patients unable to communicate with the physicians will be excluded. Comparator(s)/control Surgery is performed under general anesthesia. The original cesarean scar is usually selected. The lesions and 5–10 mm of the surrounding normal tissue are removed. If the tissue defect is too important, meshes are used for repair. For the surgery group, patients with other systemic diseases will be excluded. Main outcome(s) Main outcomes of this review including the pain relief in 1, 3, 6 and 12 months after treatment. Numeric rating scale (NRS) or visual analogue scale (VAS) will be used to measure. Measures of effect Main outcomes are expressed as mean ± standard deviation (SD). Additional outcome(s) Diameter of the nodule; Amount of bleeding; Hospital stay; Immediate pain score; the complications of HIFU ablation and surgery (e.g. skin burn, intestinal injury ); Recurrence of the AWE; Diameter of the nodule: use ultrasound examination at 1, 3, 6 and 12 months to evaluate the change of the nodules Amount of bleeding: estimated by the surgeon Hospital stay: record the number of days from admission to discharge Immediate pain score : use NRS or VAS the complications of HIFU ablation and surgery (e.g. skin burn, intestinal injury ) : calculate the incident of significant complications and adverse events Recurrence of the AWE: include symptom recurrence rate, re-intervention rate Measures of effect Continuous variables are expressed as mean ± standard deviation (SD) Categorical variables are expressed as frequency and percentage. Data extraction (selection and coding) Study selection: Two independent investigations will perform study selection according to the eligibility criteria. Firstly, the titles and abstracts of the articles will be screened. Secondly, we will collect all relevant articles for full-text assessment. Data extraction: Two investigators will independently extract data from the articles. We will record study characteristics such as the first author, time of publication, study design, treatments, characteristics of participants, duration of follow-up, and outcome measures. We will extract the mean ± standard deviation (SD) or the median of continuous data and the number of positive cases of dichotomous data. Risk of bias (quality) assessment We will use the Newcastle Ottawa Scale (NOS) for assessing the quality of studies eligible for quantitative analysis based on the recommendation of the Cochrane Collaboration. Strategy for data synthesis We will use RevMan 5.4 for statistical analysis. We will assess statistical heterogeneity by Cochran‘s Q, and inconsistency will be estimated by the I² statistic. I² with a value greater than 50% will provide evidence for substantial heterogeneity between studies. Random effect model can be used if studies have heterogeneity, and fixed effect model can be used if homogeneous. We synthesized the relative risk (RR) with a 95% confidence interval (CI) for dichotomous data (the incident of significant complications and adverse events; symptom recurrence rate, re-intervention rate) and mean difference (MD) a 95% CI for continuous data (NRS or VAS score; the duration of hospital stay; amount of bleeding). Analysis of subgroups or subsets Patients will be divided into two subgroups based on whether lesion invades the muscular layer. Then we will use RevMan 5.4 for subgroups analyses. Contact details for further information

Qiu, W., et al. (2022). "Effectiveness and safety of weekly therapy versus 3-weekly therapy of paclitaxel plus carboplatin in women with ovarian cancer: a protocol of systematic review and meta-analysis." BMJ Open 12(3): e053182.
	Introduction: Network meta-analyses have confirmed that paclitaxel plus carboplatin could improve progression-free survival (PFS) and overall survival (OS) compared with platinum alone. However, detailed implementation schedule (weekly or 3-weekly therapy) was not specified in clinical practice guidelines. Evidence from studies is also inconsistent. We will conduct a systematic review and meta-analysis to evaluate the benefits and harms of weekly therapy and 3-weekly therapy of paclitaxel combined with carboplatin in women with ovarian cancer.; Methods: We will search PubMed, EMBASE and the Cochrane Library databases to include relevant randomised controlled trials comparing weekly therapy versus 3-weekly therapy of paclitaxel combined with carboplatin for women with ovarian cancer. Random-effects model will be used to pool data for patient-reported outcomes including survival rate, OS, PFS and adverse events. Grading of Recommendation, Assessment, Development and Evaluation approach will be used to rate the quality of evidence.; Ethics and Dissemination: This systematic review and meta-analysis will be based on published data and does not therefore require specific ethical approval or consent for participation. The results will be published in a peer-reviewed journal.; Osf Registration Number: 10.17605/OSF.IO/GJUMA.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Qiushu, L., et al. (2020). "Eight chemotherapy regimens in treatment of low-risk gestational trophoblastic neoplasms: A meta-analysis." Cancer Research and Clinic 32(12): 854-861.
	Objective To systematically evaluate the efficacy and safety of 8 chemotherapy regimens in treatment of low-risk gestational trophoblastic neoplasms. Methods PubMed, Cochrane library, EMbase, Medline, Wanfang, VIP and CNKI were retrieved by computer, and the retrieval period was from database establishing time to October 2019. Stata 13.0 was used to draw the mesh diagram. Revman 5.3 and GeMTC software were used for direct and network meta-analysis respectively. Results There were 13 randomized controlled trials and 8 chemotherapy regimens. Direct meta-analysis showed that the pathological complete remission (PCR) rate of pulsed actinomycin D (act-D) was better than that of pulsed methotrexate (MTX), and the difference was statistically significant (OR = 0.21, 95% CI 0.08-0.55, P < 0.05). Network meta-analysis showed that the PCR rate of 5 d-act-D regimen and MTX + act-D regimen was better than that of MTX + folic acid, and the difference was statistically significant (OR = 0.11, 95% CI 0.01-0.71; OR = 0.03, 95% CI 0.00 0.75, all P < 0.05); PCR rate of pulsed IV act-D was better than that of pulsed MTX, and the difference was statistically significant (OR = 0.19, 95% CI 0.04-0.79, P < 0.05). The incidence of neutropenia in pulsed MTX and pulsed act-D was lower than that in 5 d-MTX, and the differences were statistically significant (OR > 100, 95% CI 2.43->100; OR > 100, 95% CI 1.84->100). The incidence of thrombocytopenia in 8 d-MTX 8 folic acid, pulsed MTX and pulsed act-D was lower than that in 5 d-act-D, and the differences were statistically significant (OR = 0.00, 95% CI 0.00-0.75; OR = 0.00, 95% CI 0.00-0.28; OR > 100, 95% CI 1.35->100, all P < 0.05). Pulsed MTX and pulsed act-D was lower than that in MTX+act-D, and the differences were statistically significant (OR = 0.00, 95% CI 0.00-0.27; OR = 0.00, 95% CI 0.00-0.72). The probability ranking diagram showed that 5 d-act-D and MTX 8 act-D had more advantages in terms of effectiveness; in terms of safety, pulsed MTX and pulsed act-D had better therapeutic effects. Conclusions MTX+act-D and 5 d-act-D have higher PCR rate and shorter treatment cycle. However, the incidence of adverse reactions, such as thrombocytopenia is higher compared with other treatment regimens. It is necessary to do more high-quality and large-scale researches to find out the optimal plan.Copyright © 2020 Chinese Medical Association Publishing House Co. Ltd. All rights reserved.

Qiuyuan, L. and D. Xiyuan (2022). "The Effect of Decreased Thickness in Response to Progesterone on Clinical Outcomes in Frozen-thawed Embryo Transfers: A Systematic Review."
	Review question This systematic review would be conducted to investigate how does decreased thickness in response to progesterone impact on clinical outcomes compared to no change or increased endometrial thickness? Searches There was no restriction on language. (decreased thickness OR thickness change)AND(frozen-thawed embryo transfer) would be searched in MEDLINE and Web of Science. Types of study to be included Randomized control trials, Case-control study, Cohort studies, Cross-sectional study. Condition or domain being studied assisted reproductive technology, frozen-thawed embryo transfer, endometrial thickness Participants/population Inclusion: women who underwent frozen-thawed embryo transfers. Exclusion: The exclusion criteria were women with uterine malformation, endometriosis, adenomyosis, and endometrial polyps or submucosae myomas as determined hysteroscopy that may affect embryo implantation. Intervention(s), exposure(s) Decreased endometrial thickness in response to progesterone in frozen-thawed embryo transfers. Comparator(s)/control No change or increased endometrial thickness in response to progesterone in frozen-thawed embryo transfers. Main outcome(s) 1.clinical pregnancy rates; 2.Live birth rate. Measures of effect 1. Clinical pregnancy was defined by ultrasound scan of at least one gestational 4 6 weeks after embryo transfer. Ectopic pregnancy and spontaneous miscarriage were taken as clinical pregnancy. Clinical pregnancy rate = number of cycles with clinical pregnancy / number of FET cycles *100%; 2.Live birth was defined as one or more live babies delivered beyond 28 weeks of gestation. Live birth rate = number of cycles with live births / number of transfer cycles*100%. Additional outcome(s) 1. Ectopic pregnancy rate; 2. Early miscarriage rate. Measures of effect 1. Ectopic pregnancy rate= number of cycles with Ectopic pregnancy / number of cycles with clinical pregnancy*100%. 2. A miscarriage that occurred before 12 weeks was defined as an early miscarriage. Early miscarriage rate = number of cycles with early miscarriage / number of cycles with clinical pregnancy*100%. Data extraction (selection and coding) The following characteristics of the studies were taken into consideration:Trial characteristics: Year and location of the trial (single or multi-centre), type of trials, study population with sample size calculation, method of randomisation, method of allocation concealment, exclusion of participants after randomisation, proportion of and reasons fornlosses at follow up, reports of ethical approval and consent. Participants: Age, FET protocol. Intervention: the change of endometrial.Outcomes: What outcomes were reported, how the outcomes were defined and the timing of outcome measurement were recorded. Risk of bias (quality) assessment MINORS, ROBINS-1, and ROB-2 would be used as tools in this systematic to assess the risk of bias and quality assessment. Strategy for data synthesis Review Manager Software 5.4 was used to generate the unpooled forest plots. If the heterogeneity is huge, we would not synthesis the data to conduct a meta-analysis. Analysis of subgroups or subsets 1.Different FET protocol; 2.Different age. Contact details for further information Qiuyuan Li 704255210@qq.com Organisational affiliation of the review The First Hospital of Lanzhou University http://www.lzu.edu.cn/ Review team members and their organisational affiliations Dr Qiuyuan Li. The First Hospital of Lanzhou University Dr Xiyuan Deng. The First Hospital of Lanzhou University Type and method of review Intervention, Systematic review Anticipated or actual start date 03 January 2022 Anticipated completion date 31 May 2022 Funding sources/sponsors None Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Embryo Transfer; Female; Humans; Pregnancy; Pregnancy Rate; Progesterone Date of registration in PROSPERO 03 February 2022 Date of first submission 04 January 2022 Details of any existing review of the same topic by the same authors Not applicable.

Qu, S., et al. (2022). "Network Pharmacology and Data Mining Approach Reveal the Medication Rule of Traditional Chinese Medicine in the Treatment of Premenstrual Syndrome/Premenstrual Dysphoric Disorder." Frontiers in Pharmacology 13: 811030.
	Premenstrual syndrome (PMS) is a common disorder that affects women of reproductive age. It is characterized by periodic mental and somatic symptoms such as irritability, depression, and breast pain during the luteal phase. Premenstrual dysphoric disorder (PMDD) is the most severe form of PMS. In recent years, the incidence of PMS/PMDD has been increasing year after year. However, due to the complex symptoms and ambiguous classification of PMS/PMDD, the limitations of present treatments, such as their poor efficacy rate, have become increasingly apparent. With its unique benefits such as syndrome differentiation and high cure rate, traditional Chinese medicine (TCM) has sparked new diagnosing and treating of PMS/PMDD. This study uses data mining methods, and statistical analysis revealed that Xiaoyao San and Chaihu Shugan San were the commonly used TCM to treat PMS/PMDD. A detailed investigation of regularly used single herbs revealed that most TCM is used as cold herbs that penetrate the liver meridian, with predominant bitter, sweet, and pungent flavors. The network pharmacology method analyzes the interactions between diseases, targets, and herbs. Meanwhile, the deep action targets and molecular mechanisms of 10 commonly used herbs for the treatment of PMS/PMDD are studied, revealing that it involves several ingredients, many targets, and different pathways. This interaction provides insight into the mechanism of action of TCM in the synergistic treatment of PMS/PMDD. It is now clear that we can begin treating PMS/PMDD with TCM using the target and mechanism revealed by the abovementioned findings in the future. This serves as an essential reference for future research and clinical application of TCM in the treatment of PMS/PMDD.Copyright © 2022 Qu, Qiao, Wang, Gao, Chen, Li, Wei and Guo.

Queiroz, J., et al. (2022). "The Dichotomous Effect of Thiamine Supplementation on Tumorigenesis: A Systematic Review." Nutrition and Cancer 74(6): 1942-1957.
	The malignant neoplastic cell is characterized by its diverse metabolic changes. It occurs in order to maintain the high rate of proliferation. The possibility of new pharmacological targets has inserted tumor metabolism as a target for recent research, emphasizing the enzymatic activity of thiamin. This review aims to elucidate the behavior of thiamin against tumor development. This is a systematic review in which studies indexed in Pubmed, Scopus, SciELO and BVS were searched using the descriptors (Thiamin OR Vitamin B1) AND (Cancer OR Malignant neoplasia) AND (Tumor metabolism). Title and abstract were read. Duplicates, literary reviews, books, conference abstracts, editorials, and papers published prior to 2010 were eliminated. 23 records were included in this review. Low doses of thiamin have been shown to be enough to stimulate tumor growth. Another population studies has shown evidence of tumor regression after correction of vitamin B1 deficiency. There is an open path for the development of new research to better assess the influence of thiamin on cancer cells. Once the connections between thiamin and the metabolism of cancer cells are fully established, new opportunities for therapeutic intervention and dietary modification will appear to reduce the progression of the disease in patients with cancer.Copyright © 2021 Taylor & Francis Group, LLC.

Quenby, S., et al. (2023). "Heparin for Women With Recurrent Miscarriage and Inherited Thrombophilia (ALIFE2): An International Open-Label, Randomized Controlled Trial." Obstetrical and Gynecological Survey 78(10): 586-587.
	Thrombophilia has been implicated in the cause of recurrent miscarriage, which affects approximately 3% of couples trying to conceive. International professional guidelines recommend heparin anticoagulation for antiphospholipid syndrome, an acquired thrombophilia responsible for approximately 15% of recurrent miscarriage, but not for other inherited thrombophilias due to an absence of evidence. Many clinicians prescribe heparin to women with recurrent miscarriage and inherited thrombophilia despite the professional recommendations. This international, open-label, randomized controlled trial aimed to compare the effect of low-molecular weight heparin (LMWH) and standard pregnancy surveillance on livebirth rates in women with recurrent miscarriage and inherited thrombophilia. Women aged 18-42 years with recurrent miscarriages who were attempting to conceive or less than 7 weeks pregnant and had an inherited thrombophilia were recruited across 40 hospitals in 5 countries. Women were randomly assigned to LMWH or no LMWH in a 1:1 ratio. Women randomized to LMWH self-administered it once a day subcutaneously, beginning as soon as possible after a positive pregnancy test and before 7 weeks of gestation and continuing throughout pregnancy. The primary study outcome was livebirth after 24 weeks of gestation. Livebirth was compared across randomized treatment groups using an chi2 test with continuity correction, then a sensitivity analysis with logistic regression to adjust for stratification factors. A total of 326 women were randomized between August 2012 and January 2021. Of these, 164 were randomized to LMWH plus standard care and 162 to standard care alone. In the standard care group, 30 patients ultimately received LMWH for thromboprophylaxis per professional treatment guidelines. The mean age of participants was 33 years, and the median number of miscarriages before randomization was 3 (interquartile range, 2-4), with two thirds of patients having a history of 3 or more miscarriages. The most common thrombophilia diagnoses were heterozygosity for factor V Leiden, prothrombin G20210A mutation, and protein S deficiency. The livebirth rate was 72% (116/162) in the LMWH group, and 71% (112/158) in the standard care group, and no statistical significant was detected between the groups even after adjustment (odds ratio, 1.08; 95% confidence interval, 0.65-1.78; P = 0.77). No differences in adverse pregnancy outcomes or complications were observed between the groups. Easy bruising was reported by 45% (73) women in the LMWH group and 10% (16) in the standard care group. This randomized controlled trial demonstrates that although LMWH is safe in women with recurrent pregnancy loss and inherited thrombophilia, it does not result in an increased live birth rate compared with standard pregnancy surveillance.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Quenby, S., et al. (2022). "Low-Molecular-Weight Heparin Versus Standard Pregnancy Care for Women with Recurrent Miscarriage and Inherited Thrombophilia (ALIFE2): an Open-Label, Phase III Randomized Controlled Trial." Blood 140: 17‐18.
	Abstract: Background Studies have shown an association between recurrent miscarriage and inherited thrombophilia. It has been hypothesized that anticoagulant therapy might reduce both number of miscarriages and adverse pregnancy outcomes in these women and this is widely practiced despite lack of solid evidence. In the absence of randomized controlled trials that assess the efficacy of low‐molecular‐weight heparin (LMWH) therapy in women with recurrent miscarriage and inherited thrombophilia, a randomized clinical trial that addresses this topic was highly needed. Methods Design: The ALIFE 2 trial was an investigator‐initiated, international open‐label randomized controlled trial. The Netherlands coordinated recruitment in 15 hospitals in the Netherlands, USA, Belgium, and Slovenia. The UK coordinated 26 sites including sites in England, Scotland, Wales and Northern Ireland. The study protocol was approved by the institutional review boards of all participating centres, and in the UK, NRES, MHRA and HRA. Written informed consent was obtained from all patients prior to randomization. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015‐002357‐35). Study population: Women (18‐42 years) who had two or more pregnancy losses and confirmed inherited thrombophilia (factor V Leiden, prothrombin 20210A mutation, antithrombin, protein C or protein S deficiency) who were actively trying to conceive or less than 7 weeks pregnant were eligible for inclusion. Women were excluded if duration of current pregnancy was 7 weeks or more, if they had an indication for anticoagulant treatment during pregnancy, a contraindication for LMWH, a known allergy for LMWH or previous enrolment in this trial. Randomisation and intervention: Women were randomly assigned (1:1) to use subcutaneous LMWH once daily (enoxaparin 40 mg, dalteparin 5,000 IU, tinzaparin 4,500 IU or nadroparin 3,800 IU) versus standard pregnancy surveillance once they had a positive urine pregnancy test. LMWH was started ≤ 7 weeks of pregnancy and continued until the end of pregnancy. Outcomes: The primary outcome measure was live birth rate. Secondary outcomes included adverse pregnancy outcomes, such as miscarriage, obstetric complications (premature delivery, pre‐eclampsia, HELLP syndrome, intrauterine growth restriction), and congenital malformations. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions to the prescribed study medication. Statistical analysis: Analysis includedall available datafrom all women who were randomized and did not withdraw consent to be followed up, as per the intention‐to‐treat principle. Exploratory subgroup analyses investigated the effect of age, number of previous miscarriages, previous live birth and type of inherited thrombophilia. Results Between August 2012 and January 2021, 10,626 women with recurrent miscarriage were assessed for eligibility, most of whom were not eligible due to absence of inherited thrombophilia. A total of 428 women were registered, of whom 326 women conceived and were randomized. 164 were assigned to the LMWH group and 162 were assigned to the standard surveillance group. The mean age was 33 years, approximately one third being 36 years or older, and the majority was of caucasian ethnicity (83%). The median number of miscarriages prior to randomization was 3, and 70% had a history of 3 or more miscarriages. The most common thrombophilia types were heterozygosity for factor V Leiden (56%), prothrombin 20210A mutation (25%), and protein S deficiency (14%). Aspirin was used as co medication in 11%. Observed live birth rates were 116/162 (71.6%) in the LMWH group and 112/158 (70.9%) in the standard surveillance group (adjusted OR 1.08 (95% CI 0.65 to 1.78)(absolute difference 0.7% (95% CI ‐9.2% to 10.6%). Adverse events were reported for 39 women (23.8%) in the LMWH group and 37 (22.8%) women in the standard surveillance group. Interpretation Compared with standard surveillance, the use of LMWH did not result in higher live birt ates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. On the basis of our findings, we do not advise routine use of LMWH in women with recurrent pregnancy loss and confirmed inherited thrombophilia, and we advise against routine testing for inherited thrombophilia in women with recurrent pregnancy loss. Disclosures: Middeldorp: Bayer: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Abbvie: Honoraria; Viatris: Honoraria; Sanofi: Honoraria; Norgine: Honoraria; GSK: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Astra Zeneca: Honoraria. OffLabel Disclosure:: We present a RCT where we assess the efficacy of low‐molecular‐weight heparin (LMWH) to improve live birth in women with inherited thrombophilia and a history of recurrent miscarriage. This is not a labeled indication of LMWH.

Quintairos Ricardo de, A., et al. (2022). "Conservative versus Radical Surgery for Women with Deep Infiltrating Endometriosis: Systematic Review and Meta-analysis of Bowel Function." Journal of Minimally Invasive Gynecology 29(11): 1231-1240.
	Objective: To assess bowel function in women with deep infiltrating endometriosis according to surgical approach (radical vs conservative).; Data Sources: Five databases were searched from 1970 to September 2021 to retrieve studies comparing radical (colorectal segmental resection) and conservative (shaving or discoid excision) surgery for bowel function in women with deep infiltrating endometriosis.; Methods of Study Selection: No language restriction was applied. Two reviewers extracted and combined data from the included studies, applying a meta-analytic model with random effects in all calculations. Results are expressed in risk ratio (RR) with 95% confidence interval (CI). Assessment of risk of bias and quality of evidence was performed by the Newcastle-Ottawa and Grading of Recommendations, Assessment, Development and Evaluation, respectively.; Tabulation, Integration, and Results: We included 13 studies in our meta-analysis, and most of them were of nonrandomized design. Conservative surgery had fewer events of constipation and frequent bowel movements when compared with radical surgery (RR, 2.31; 95% CI, 1.21-4.43; I 2 = 0%; 3 studies; RR, 2.80; 95% CI 1.17-6.75; I 2 = 0%; 2 studies, respectively). Defecation pain, anal incontinence loss, minor and major lower anterior resection syndrome, and Clavien-Dindo complications grade I to IV showed no statistically significant difference between surgeries. Grading of Recommendations, Assessment, Development and Evaluation assessment was low to very low for all outcomes.; Conclusion: Conservative surgery (shaving or discoid excision) presented fewer events of constipation and frequent bowel movements than colorectal segmental resection. There was a very low quality of evidence to provide recommendations regarding bowel function. (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Rabia, N., et al. (2022). "Efficacy and Safety of Oral GnRH antagonists in Patients With Uterine Fibroids: A Systematic Review."
	Review question Are oral GnRH antagonists safe in the treatment of uterine fibroids? Are oral GnRH antagonists effective in the treatment of uterine fibroids? Searches A literature search was performed on PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov with MeSH and Emtree terms “Leiomyoma” and “Gonadotropin-Releasing Hormone” from the inception of literature till 07/25/2021 by following the PICO framework. Types of study to be included We included all randomized clinical trials, non-randomized clinical trials, and observational studies. Case reports and case series were excluded. Condition or domain being studied Uterine fibroids. Uterine fibroids are known to cause abnormal menstrual pain and increased uterine bleeding. We reviewed the efficacy and safety of newer drug therapies for the treatment of uterine fibroids. Participants/population We included all clinical trials, and observational studies that provided efficacy and safety data in clinical terms, i.e., menstrual bleeding and discomfort reduction, change in the size of leiomyoma, change in uterine volume, etc. We excluded all preclinical studies, case reports, meta-analyses, review articles, and clinical studies irrelevant to the study question. Intervention(s), exposure(s) We reviewed the efficacy and safety of oral GnRH antagonists studied in randomized and non-randomized clinical trials. Oral GnRH antagonists are the newer form of treatment and require less expertise and monitoring as compared to injectable forms previously used. We included all adult female patients suffering from uterine fibroids (leiomyoma). Comparator(s)/control The comparison group includes adult female patients suffering from uterine fibroids treated with a placebo only. Main outcome(s) menstrual bleeding and discomfort reduction, change in the size of leiomyoma, change in uterine volume, and >grade 3 adverse events. Additional outcome(s) Hemoglobin concentration increased >2g/dl from baseline, amenorrhea, QoL symptom severity score reduction, change in BMD (Lumbar Spine), Change in BMD (Femoral Neck) Data extraction (selection and coding) Data were extracted using Microsoft Excel. It included characteristics of the study, baseline characteristics of participants (number, age, BMI, bleeding and pelvic discomfort scoring, menstrual blood loss, mean hemoglobin, total uterine volume, largest leiomyoma volume), treatment drugs, efficacy measures (menstrual bleeding and discomfort reduction, change in the size of leiomyoma, change in uterine volume), and toxicity (>grade 3 adverse events). Risk of bias (quality) assessment We used RoB-II tool to assess the risk of bias in the included clinical studies. Strategy for data synthesis The data will be synthesized in the form of proportions for patients with amenorrhea, suppression of bleeding, and an increase in hemoglobin. Mean change/reduction was used to assess change in blood loss, leiomyoma volume, uterine volume, and bleeding & pelvic discomfort score change from baseline. The least-square mean difference was used for menstrual blood loss. Analysis of subgroups or subsets Patients treated with delayed oral GnRH antagonist. Patients treated with oral GnRH antagonist. Patients treated with oral GnRH antagonist combinations. Patients treated with placebo. Contact details for further information Muhammad Ashar Ali asharalianwar94@gmail.com Organisational affiliation of the review Beth Israel Deaconess Medical Center, Harvard Medical School Review team members and their organisational affiliations Dr Rabia Niaz. King Edward Medical University Dr Muhammad Ashar Ali. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Type and method of review Intervention, Systematic review Anticipated or actual start date 08 October 2021 Anticipated completion date 25 April 2022 Funding sources/sponsors None Conflicts of interest Language English Country Pakistan, United States of America Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Uterine Neoplasms Date of registration in PROSPERO 25 April 2022 Date of first submission 25 March 2022

Rachel, Z., et al. (2023). "Systematic review of GnRH agonists and antagonists for treatment of chronic pelvic pain and abnormal uterine bleeding in patients with symptomatic endometriosis."
	Review question What is the utility of GnRH antagonists with and without add back therapy in the treatment of endometriosis in reproductive age women as compared to GnRH agonists? What is the effect of these medications on management of pain, bleeding, need for surgeries, and side effects? Searches PubMed Embase ClinicalTrials.gov Cochrane Web of Science Menstrual Disorders and Subfertility Group (MDSG) Specialized Register of controlled trials Types of study to be included Prospective studies Case series Retrospective studies Systematic reviews Nonsystematic reviews Randomized control trials Condition or domain being studied Endometriosis Participants/population Reproductive age women (premenopausal over age 18) with any of the following: Surgical diagnosis of endometriosis, Moderate or severe endometriosis associated pain, Ovarian endometrioma within the previous year confirmed by MRI or US, Physical exam findings concerning for endometriosis - restricted uterine mobility, pelvic tenderness, induration of the Douglas cavity Intervention(s), exposure(s) GnRH Antagonists Comparator(s)/control GnRH agonists Main outcome(s) Overall pelvic pain - pain score measurement, Dysmenorrhea - pain score measurement, Non menstrual pelvic pain - pain score measurement, Use of supplementary NSAIDS, Use of supplementary opioids, Dyspareunia, Dyschezia, Biomarkers - Serum estradiol level, progesterone, LH, FSH, Amenorrhea, Patient global impression of change, 30-item endometriosis health profile, QoL measures, Bone mineral density, Need for surgery/time to surgery, Medication side effects: Hot flashes, Headache, Nausea, Lipid profile Additional outcome(s) Not applicable Data extraction (selection and coding) PubMed, Embase, MEDLINE, and ClinicalTrials.gov will be searched to find relevant literature. The Abstrackr platform will be used for double abstract screening. Titles of studies retrieved using the search strategy will be screened independently by two review authors to identify studies that potentially meet the inclusion criteria. The full text of these potentially eligible studies will be retrieved and independently assessed for eligibility by two review team members. Data will then be abstracted into excel spreadsheets or SRDR+. Extracted information will include: study setting; study population and participant demographics and baseline characteristics; details of the intervention and control conditions; study methodology; recruitment and study completion rates; outcomes and times of measurement; suggested mechanisms of intervention action; information for assessment of the risk of bias. Two review authors will extract data independently, discrepancies will be identified and resolved through discussion. Risk of bias (quality) assessment There is risk of bias in selection of studies and bias within the studies themselves. Strategy for data synthesis We will provide a narrative synthesis of the findings from the included studies, structured around the type of intervention and outcome. We will provide summaries of intervention effects for each study by calculating risk ratios (for dichotomous outcomes) or standardized mean differences (for continuous outcomes). We anticipate there will be a limited scope for meta-analysis. However, where studies have used the same type of intervention and comparator with the same outcome measurement, we will pool the results for meta-analysis, with standardized mean differences for continuous outcomes and risk ratios for binary outcomes and calculate 95% confidence intervals and two sided p values for each outcome. Analysis of subgroups or subsets None Contact details for further information Rachel Zeuner rachel.zeuner@wmchealth.org Organisational affiliation of the review Westchester Medical Center Review team members and their organisational affiliations Dr Rachel Zeuner. Westchester Medical Center Dr Julia Keltz. Westchester Medical Center Dr Timothy Ryntz. Westchester Medical Center Dr Cara Grimes. Westchester Medical Center Dr Katya Wentzel. Westchester Medical Center Ashley Sacks. New York Medical College Rebecca Strafella. New York Medical College Aneesha Akbar. New York Medical College Adi Steinhart. New York Medical College Ms Judy Moore. Westchester Medical Cetner Type and method of review Intervention, Meta-analysis, Narrative synthesis, Systematic review Anticipated or actual start date 01 July 2023 Anticipated completion date 30 September 2023 Funding sources/sponsors No funding Conflicts of interest Language English Country United States of America Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Endometriosis; Female; Hormone Antagonists; Humans; Pelvic Pain; Uterine Diseases Date of registration in PROSPERO 16 June 2023 Date of first submission 04 June 2023

Rad, M. T., et al. (2020). "Laparoscopic intervention after ventriculoperitoneal shunt: A case report, systematic review, and recommendations." World Journal of Laparoscopic Surgery 13(1): 35-42.
	Background: In patients presenting pelvic pathology and a placed ventriculoperitoneal (VP) shunt, there is uncertainty regarding the decision whether to use laparoscopy. The aim of the article is to examine the available literature as well as sharing our own experiences operating on a patient with a VP shunt using laparoscopy. Material(s) and Method(s): We searched online libraries (PubMed, EMBASE, and Google Scholar) for all publications published between January 1975 and December 2018 on our topic. We performed a systematic review and shared our experience with laparoscopy in a patient with shunt and ovarian cancer. Result(s): The age of the patients ranged from 1 to 79 years. The operations were performed by the departments of general surgery, gynecology, and urology. The time from the shunt operation to laparoscopy ranged from 5 days to 28 years. In different articles, four important points were considered and discussed: the risk of a shunt infection or complication, technical difficulties carrying out laparoscopy in patients with a VP shunt, the necessity of routine monitoring of the intracranial pressure (ICP) intraoperatively, and perioperative strategies to avoid complications. Conclusion(s): It seems that a laparoscopic surgery in adults with a VP shunt appears to be a safe option. Based on the results of our case and the review of literature, we consider it necessary to have a neurosurgical consult performed prior to surgery, to have the procedure be carried out by an experienced surgeon, and to avoid complications by implementing recommended precautions.Copyright © The Author(s).

Radtke, S., et al. (2024). "Reducing patient's perception of postoperative vaginal bleeding after laparoscopic hysterectomy via independent closure of the vaginal cuff angles (RCT)." European Journal of Obstetrics, Gynecology, and Reproductive Biology 294: 111-116.
	STUDY OBJECTIVE: Determine if independently suturing the vaginal cuff angles in addition to running barbed suture has an effect on patients' perception of postoperative bleeding after laparoscopic hysterectomy. DESIGN: Randomized controlled trial. SETTING: University-based medical center. PATIENTS: Females ages 18-60 undergoing laparoscopic hysterectomy. INTERVENTIONS: Patients were randomly assigned to either cuff closure via single layer of barbed suture (control) vs adding figure-of-eight stitches at each angle (intervention). A survey was given between 10 and 25 days after surgery inquiring about bleeding and dyspareunia. A second survey was given between postoperative days 90-114. Chart review was performed to record emergency room visits, complications, infections, and reoperations during the first 90 postoperative days. RESULTS: n = 117 patients were analyzed. 62 (control) and 55 (intervention). Groups were similar in terms of age (42.92 v 44.29p =.35), BMI (33.79 v 34.06p =.85), diabetes (5.26 % (3/55) v 15.09 % (8/53) p =.08) p =.97). Bleeding was decreased in intervention arm (24.19 % (15/62) v 9.09 % (5/55) p =.03). Median (IQR) pelvic pain score was similar (2.0 (0-5.0) v 2.0 (0-4.0) p =.26). Median total operative time (IQR) (129 min (102, 166) v 139 min (120, 163) p =.39) and median EBL (IQR) (50 mL (30-75) vs 50 mL (20-75) p =.43) were similar. Cuff closure in seconds (IQR) was higher in intervention group (373 sec (323, 518) v 571 sec (520, 715) p <.01). 8/60 control patients visited the ED (13.33 %) v 7/54 (12.96 %) p =.95. Readmissions (1.67 % (1/60) v 1.85 % (1/55) p = 1), re-operations (0 % (0/60) v 1.85 % (1/55) p =.47) and postoperative infections (5.0 % (3/60) v 1.85 % (1/54) p =.62) were similar. Secondary survey showed no significant difference in bleeding (15.38 % (4/26) v 4.35 % (1/23) p =.35) and SF-36 results were similar. CONCLUSION: Independently suturing the vaginal cuff angles reduces patients' perception of vaginal bleeding in the early postoperative period. Incidence of complications, reoperations, and long-term quality of life are similar.

Radtke, S., et al. (2021). "Utilizing Telemedicine for Delivery of Postoperative Care Following Minimally Invasive Gynecologic Surgery: A Randomized Controlled Trial." Gynecology and Minimally Invasive Therapy 10(3): 148-153.
	OBJECTIVES: Determine if patient satisfaction is greater after delivering postoperative care via telemedicine following minimally invasive gynecologic surgery. MATERIALS AND METHODS: University-based outpatient clinic; Randomized controlled trial (Canadian Task Force classification I). Females between 18 and 60 years of age scheduled to undergo laparoscopic hysterectomy or laparoscopic excision of endometriosis were invited to participate. Eligible patients were randomized to receive postoperative care either through a traditional office visit or via telemedicine. PSQ-18 satisfaction surveys were performed by phone after the visit. RESULTS: Forty-one patients were analyzed out of which 25 were in the office group and 16 in the telemedicine group. Groups were homogenous to age (41.4 vs. 43.3 p. 48), body mass index (31.9 vs. 30.6 P = 0.52), distance in miles from home (12.7 vs. 12.4 P = 0.92), and parity (P = 0.51). PSQ-18 questionnaire was scored and each category was compared between the office and telemedicine groups. When comparing medians (interquartile range), the general satisfaction and time spent with doctor categories were significantly higher in the telemedicine group (4.0 [4.0, 4.5] vs. 4.5 [4.5, 5.0] P = 0.05), (4.0 [4.0, 4.5] vs. 4.5 [4.0, 5.0] P = 0.05). The remainder of the categories analyzed were not different between groups Technical Quality (4.0 [3.8, 4.5] vs. 4.5 [3.9, 5.0] P = 0.13), Interpersonal Manner (4.0 [4.0, 4.5] vs. 4.5 [4.0, 5.0] P = 0.34), Communication (4.5 [4.0, 4.5] vs. 4.5 [4.3, 5.0] P = 0.21), Accessibility and Convenience (4.0 [3.5, 4.5] v 4.0 [3.6, 4.5] P = 0.84). A chart review was performed, examining the first 30 days after surgery. One (4%) patient in the office group went to the ER after postoperative visit, and 0 in the telemedicine group (P = 0.42). CONCLUSION: Postoperative care via telemedicine after gynecologic surgery results in higher patient satisfaction.

Radwan, R. W., et al. (2021). "Vertical rectus abdominis flap (VRAM) for perineal reconstruction following pelvic surgery: A systematic review." Journal of Plastic, Reconstructive and Aesthetic Surgery 74(3): 523-529.
	Background: The vertical rectus abdominis myocutaneous (VRAM) flap is an established technique employed to reconstruct pelvic and perineal defects not amenable to primary closure. The aim of this study was to systematically review the morbidity of VRAM flap reconstruction following exenterative pelvic surgery. Material(s) and Method(s): A systematic literature search was conducted by using Medline, EMBASE, and Cochrane databases. Abstracts of all studies published from inception to November 2019 were identified. Search terms used included 'vertical rectus abdominis myocutaneous', 'vertical rectus abdominis musculocutaneous' and 'VRAM'. Only studies that described outcomes when a VRAM flap was used during exenterative pelvic surgery were included; case reports were excluded. The primary outcome measure was VRAM flap morbidity. Secondary outcome measures included donor site morbidity and hospital length of stay. Result(s): Sixty-five studies with a total of 1827 patients were identified and included. Perineal reconstruction was most commonly performed following abdominal perineal excision of the rectum (APER) (n = 636 and 34.8%). Median patient age at surgery ranged from 38 to 78 years. Mean perineal flap morbidity was 27%, with a complete flap loss rate of 1.8% and a perineal hernia rate of 0.2%. Mean donor site morbidity was 15%, with an abdominal dehiscence rate of 5.5% and an incisional hernia rate of 3.3%. Conclusion(s): While overall morbidity after VRAM flap reconstruction in pelvic visceral surgery is high; the risk of major complications remains low. These data are important when counselling patients for surgery.Copyright © 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons

Raffone, A., et al. (2022). "Impact of ovarian preservation on survival for women with endometrial carcinoma." Cochrane Database of Systematic Reviews 2022(10): CD015307.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. Primary objective will be to evaluate the impact of ovarian preservation on survival outcomes of women with endometrial cancer, while secondary objectives will be to evaluate the impact of ovarian preservation on adverse events and quality of life (QoL).Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Raffone, A., et al. (2022). "Comparison between Laparoscopic and Robotic Approach for Sentinel Lymph Node Biopsy in Endometrial Carcinoma Women." Journal of Personalized Medicine 13(1).
	Robotic surgery has been approved as an alternative to laparoscopy to improve surgical outcomes. There is neither a consensus nor a systematic assessment of the literature about the superiority of the robotic approach over the laparoscopic one for sentinel lymph node (SLN) biopsy in endometrial carcinoma (EC) women. Therefore, a systematic review and meta-analysis was performed to compare the laparoscopic and robotic approaches for SLN biopsy in EC patients. Five electronic databases were queried from their inception to May 2022 for peer-reviewed studies, comparing such approaches in SLN biopsy in EC patients. The rate of detected SLN, dissected SLN, intraoperative and postoperative complications, conversion to laparotomy, number of dissected SLN, and SLN identification and dissection time were compared between the laparoscopic and robotic approaches for SLN biopsy in EC patients. Odds ratios with 95% confidence intervals were calculated when possible. Two studies with 660 EC women (364 who had undergone laparoscopy, and 296 who had robotic surgery) were included. No assessed outcome showed significant differences between the two approaches. In conclusion, the laparoscopic and robotic approaches for SLN biopsy in EC patients appeared to not differ, in terms of SLN detection, intraoperative and postoperative complications, conversion to laparotomy, number of dissected SLN, and SLN identification and dissection time.

Raffone, A., et al. (2023). "Conservative re-treatment of women with atypical endometrial hyperplasia and early endometrial carcinoma: We can hope, at least." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.
	Background: In women with recurrent disease who were conservatively treated for atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC), the reasons why conservative treatment was chosen persist and outcomes of performing a conservative re-treatment are unclear, as pooled estimates on oncologic outcomes of such a re-treatment are lacking.; Objectives: To provide pooled estimates of oncologic outcomes of conservative re-treatment in women with recurrent AEH or EC.; Search Strategy: A systematic review and meta-analysis was performed by searching six electronic databases from their inception to March 2022.; Selection Criteria: Studies that allowed extraction of data about oncologic outcomes of conservative re-treatment of women with recurrent AEH and EEC after a conservative treatment.; Data Collection and Analysis: Pooled prevalence of complete response (CR), poor response (PR), and recurrence after conservative re-treatment was calculated.; Main Results: Fifteen studies (12 retrospective and 3 prospective) with 492 women (42.1% AEH and 57.9% EEC) were included in the systematic review, and 10 studies (8 retrospective and 2 prospective) were suitable for the meta-analysis. Pooled prevalence was 85.3% (95% confidence interval [CI] 77.0%-91.0%) for CR, 14.7% (95% CI 9.0%-23.0%) for PR, and 40.4% (95% CI 15.5%-71.4%) for recurrence.; Conclusions: Conservative re-treatment in AEH or EC recurrent women has a high CR rate and acceptable recurrence rate that might allow it to be considered a safe and viable option, at least as a first round of conservative treatment. Women with an unsatisfied desire for motherhood or with high surgical risk might avoid hysterectomy and attempt childbearing or spare high-risk surgery. (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Rafique, M., et al. (2019). "The effectiveness of Bupivacaine as a pre-emptivepudendal block among patients undergoing vaginal surgeries: meta-analysis of randomized controlled trials." ResearchSquare.
	Background: Pre-emptive analgesia using pudendal nerve block (PNB) with bupivacaine is commonly used in clinical practice during pelvic floor and vaginal surgeries. However, its effectiveness is unclear. To update the evidence base we summarised short- and intermediate-term outcomes of pre-emptive analgesia using pudendal nerve block with bupivacaine as an approach in the management of pelvic floor and vaginal surgeries. Methods: We searched the CENTRAL, PubMed, ClinicalTrials.gov, google scholar and Open Grey from inception until April 2019. The citation lists of relevant papers were also searched. Randomized controlled trials (RCTs) of women who underwent perineal, pelvic floor or vaginal surgeries and received pre-emptive analgesia using a pudendal nerve block were included. Two authors independently screened and selected eligible trials as well as performed data extraction and quality assessment. Disagreements were resolved via consensus and an adjudicator was involved when consensus was not achieved. Data was narratively synthesized, when possible, data was pooled in RevMan 5 using random effects model. Results: Four RCTs with a total of 349 participants were eligible for inclusion. We found evidence of small effect for improvement in post-operative pain scores; requirements for opioids, SMD: -0.89 (95% CI: -1.19, -0.59) and non-steroidal anti-inflammatories SMD -1.04 (95% CI: -1.64, -0.43) in favour of the PNB versus control group. The risk ratio for adverse effects 0.42 (95% CI: 0.18, 0.99) favoured PNB. There was no significant difference between groups for length of hospital stay, MD: -0.82 (95% CI: -5.34, 3.69) and return to normal activity. Conclusion:We found inconclusive evidence that pre-emptive pudendal block using bupivacaine may improve postoperative pain and recovery in perineal, pelvic floor or vaginal surgeries. However, due to the scant and poor quality of evidence included in this systematic review, well-designed and adequately powered RCTs that adhere to reporting guidelines and evaluate key outcomes are needed to inform clinical guidelines on the use of pre-emptive pudendal block. Key words:pre-emptive analgesia, bupivacaine, pudendal nerve block, vaginal surgery, pelvic organ prolapse, systematic review, meta-analysis

Rahimy, E., et al. (2021). "Phase II trial evaluating efficacy of a Fitbit program for improving the health of endometrial cancer survivors." Gynecologic Oncology 161(1): 275-281.
	BACKGROUND: Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors. METHODS: Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months. RESULTS: The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005). CONCLUSIONS: Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.

Rahman, S. A., et al. (2022). "A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women." Sleep 45(3): zsac007.
	Study Objectives: The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for the vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. Method(s): In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores >=15, and >30 min of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n = 27) or placebo (n = 29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. Result(s): Mean baseline ISI scores were 18.1 (95% CI, 16.8 to 19.4) and 18.3 (95% CI, 17.2 to 19.5) in the suvorexant and placebo groups, respectively (p = .81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant (-8.1 [95% CI, -10.2 to -6.0]) compared to placebo (-5.6 [95% CI, -7.4 to -3.9], p = .04). Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p <. 01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparisons. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. Conclusion(s): These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia.Copyright © 2022 The Author(s).

Rahn David, D., et al. (2023). "Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse." American Journal of Obstetrics and Gynecology 229(3): 309.e301-309.e310.
	Background: Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen.; Objective: This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse.; Study Design: This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights).; Results: Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference, -0.33 points; 95% confidence interval, -0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs +0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01).; Conclusion: Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prol pse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rahn, D. D., et al. (2021). "Design of a Randomized Clinical Trial of Perioperative Vaginal Estrogen Versus Placebo With Transvaginal Native Tissue Apical Prolapse Repair (Investigation to Minimize Prolapse Recurrence of the Vagina using Estrogen: IMPROVE)." Female Pelvic Medicine & Reconstructive Surgery 27(1): e227-e233.
	OBJECTIVES: To provide the rationale and design for a randomized, double-blind clinical trial of conjugated estrogen vaginal cream (applied for at least 5 weeks preoperatively and continued twice-weekly through 12 months postoperatively) compared with placebo in postmenopausal women with symptomatic pelvic organ prolapse undergoing a standardized transvaginal native tissue apical repair. METHODS: Study population, randomization process, study cream intervention, masking of participants and evaluators, placebo cream manufacture, standardized surgical intervention, and collection of adverse events are described. The primary outcome of surgical success is a composite of objectively no prolapse beyond the hymen and the vaginal cuff descending no more than one third the vaginal length; subjectively, no sense of vaginal pressure or bulging; and no retreatment for prolapse at 12 months. Time-to-failure postoperatively will be compared in the 2 groups with continued surveillance to 36 months. Secondary outcomes assessed at baseline, preoperatively (ie, after at least 5 weeks of study cream), and postoperatively at 6 month intervals include validated condition-specific and general quality-of-life metrics, overall impression of improvement, sexual function, vaginal atrophy symptoms, and body image. Challenges unique to this study include design and manufacture of placebo and defining and measuring study drug adherence. RESULTS: Recruitment of 204 women is complete with 197 randomized. There have been 174 surgeries completed with 15 more pending; 111 have completed their 12 month postoperative visit. CONCLUSIONS: This trial will contribute evidence-based information regarding the effect of perioperative vaginal estrogen as an adjunct therapy to standardized transvaginal native tissue prolapse surgical repair.

Raimondo, D., et al. (2022). "Cost-effectiveness analysis of ovarian tissue cryopreservation and transplantation for preservation of fertility in post-pubertal oncological women submitted to high-risk gonadotoxic chemotherapy." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 159(1): 116-121.
	Objective: To study the economic impact of ovarian tissue cryopreservation and transplantation (OTC) in post-pubertal patients who underwent high-risk gonadotoxic chemotherapy.; Methods: A decision tree model was used to determine the live birth rate and cost-effectiveness of OTC versus non-OTC. The incremental cost-effectiveness ratio (ICER) was calculated. A sensitivity analysis was performed under the assumption that the costs of ovarian cortex retrieval, cryopreservation, and storage for patients with cancer might be covered by the national health system or health insurance.; Results: Patients had the greatest probability of achieving live birth after high-risk chemotherapy when they underwent OTC versus non-OTC. Although cryopreservation of ovarian tissue results in higher live birth rates, it is always more expensive. Cost-effectiveness increases when the majority of patients completes the path of tissue cryopreservation plus transplantation after 5 years.; Conclusion: Although OCT has been demonstrated as a procedure for effective fertility preservation in fertility-age women with cancer, no cost-effectiveness analysis has been performed until now. This model could help healthcare systems to allocate coverage for OCT. (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Raimondo, D., et al. (2020). "Cellulose absorbable barrier for prevention of de-novo adhesion formation at the time of laparoscopic myomectomy: A systematic review and meta-analysis of randomized controlled trials." European Journal of Obstetrics, Gynecology, and Reproductive Biology 245: 107-113.
	Objective: Myomectomy is the standard surgical treatment for symptomatic uterine leiomyomas, especially for patients wishing to preserve their fertility. However, this procedure is associated with adhesion formation. Several strategies have been proposed to reduce them. Cellulose absorbable barrier is widely used. We aimed to assess its effectiveness in the prevention of de-novo adhesion formation after laparoscopic myomectomy.; Study Design: A systematic review and meta-analysis was performed by searching electronic databases (i.e. MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) from their inception until May 2019. We included all randomized clinical trials (RCT) comparing use of cellulose absorbable barrier (i.e. intervention group) with either placebo or no treatment (i.e. control group) in the prevention of de-novo adhesion formation at the time of laparoscopic myomectomy. Primary and secondary outcomes were defined before data extraction. The primary outcome was the incidence of adhesions at second-look laparoscopy. The secondary outcome was the operative time.; Results: Three RCT, including 366 participants, were included. All trials evaluated women undergoing laparoscopic myomectomy who were randomized to intervention (either oxidized regenerated cellulose or carboxymethylcellulose powder adhesion barrier) or no treatment (control group). Women who received treatment had significantly lower incidence of adhesions at the second look laparoscopy (RR 0.63, 95 % CI 0.40-0.99). Interventions with use of cellulose absorbable barrier were 4 min longer (MD 4 min, 95 % CI 2.82-5.18).; Conclusion: Use of cellulose absorbable barrier at the time of laparoscopic myomectomy reduces the risk of postoperative adhesions.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Raja, D. D., et al. (2022). ""EFFICACY OF INTRATHECAL NALBUPHINE OVER FENTANYL AS ADJUVANT WITH ROPIVACAINE IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES"." Journal of Cardiovascular Disease Research 13(8): 691-701.
	Background: Ropivacaine also showed the advantage of lesser motor blockade making it preferable when early mobilization is suggested. This helps to hasten the postoperative recovery [3]. Since its introduction into market in 1996, Ropivacaine has been put to extensive use in epidural, intrathecal and peripheral nerve blocks. OBJECTIVE(S): To measure, compare and analyse the below mentioned parameters at regular intervals among subjects undergoing lower abdominal and lower limb surgeries 1. Onset and duration of analgesia 2. Motor blockade 3. Hemodynamic parameters 4. Spo2 (oxygen saturation), respiratory rate 5. Postoperative period pain MATERIAL & METHODS: Study Design: A prospective, randomized, comparative study. Study area: The study was conducted in the Department of Anesthesiology, Malla Reddy Institute of Medical Sciences a tertiary care centre in Hyderabad. Study Period: Jan. 2021 - Dec. 2021. Study population: All the patients who were undergoing the elective lower abdominal and limb surgeries in the department of anesthesiology during the study period. Sample size: study consisted of 60 cases. Sampling method: Simple random method. Study tools and Data collection procedure: All the patients meeting the inclusion criteria were taken into the study. A pre- designed, pre-tested, semi structured and pre-coded proforma was used for recording all the findings. After obtaining Ethical clearance from the Institutional Ethical Committee, study was conducted. After taking informed consent, patients were posted for lower abdominal and lower limb surgeries and fulfilling the inclusion criteria were enrolled for the study. Documents providing information on the proposed study and form for obtaining consent (consent form) were provided to the patient in the pre-anesthetic clinic. Pre anaesthetic assessment of each patient including detailed medical history such as diabetes mellitus, hypertension, pulmonary tuberculosis, allergy to drugs, bronchial asthma, epilepsy and bleeding disorders will be taken. Result(s): Comparison of the Modified Ramsay Sedation Score between the two groups shows that Modified Ramsay Sedation Score at 30, 120, 150 and 180 mins is higher in GROUP-N and is statistically not significant with a p value of > 0.05. Comparison of the Modified Ramsay Sedation Score between the two groups shows that Modified Ramsay Sedation Score at 60 and 90 mins is higher in GROUP-N and is statistically significant with a p value of < 0.001. CONCLUSION(S): To conclude, Nalbuphine (500microg) seems to be an attractive alternative to 25microg Fentanyl as an adjuvant to spinal ropivacine in surgical procedures as it provides good quality of intraoperative analgesia, hemodynamically stable conditions, and excellent quality of postoperative analgesia as per our study.Copyright © 2022 EManuscript Technologies. All rights reserved.

Rajashekar, S., et al. (2022). "Spironolactone Versus Oral Contraceptive Pills in the Treatment of Adolescent Polycystic Ovarian Syndrome: A Systematic Review." Cureus 14(5): e25340.
	Polycystic ovarian syndrome (PCOS) is a multi-system endocrinopathy that affects women of reproductive age. Due to features that coincide with puberty, it frequently remains undiagnosed in adolescent females. The lack of evidence on management alternatives has resulted in significant variation in practice. This systematic review evaluated the therapeutic advantages and adverse effects of a regularly used therapy option, combined oral contraceptive pills (COC/OCP) with spironolactone (SP), a newer alternative that may be used alone or in conjunction with other drugs to treat adolescent PCOS. A literature search was conducted using PubMed, PubMed Central, Scopus, and Google Scholar. It was restricted to studies published in English between 2021 and 2011 that discussed the management of adolescent PCOS with COC, SP, or both. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Two reviewers independently examined the content of the included studies using appropriate quality assessment tools. Four meta-analyses, four randomized controlled trials (RCTs), and one traditional review were found to be eligible. After extensive analysis, we concluded that SP, alone or in combination, is far safer than COC. However, COC treats more PCOS-associated symptoms than SP, including acne and menstrual irregularities, while also providing contraceptive benefits. However, SP monotherapy is cardioprotective and therapeutic when combined with other drugs. Long-term COC use has been linked to an increased risk of venous thromboembolism, hypertension, dyslipidemia, low-density lipoprotein (LDL) elevation, dysglycemia, and cancer in women.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Rajashekar et al.)

Ramadan, A., et al. (2022). "Safety and efficacy of oxytocin gel vs. placebo gel on postmenopausal women with vaginal atrophy: updated systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Ramadanov, N., et al. (2021). "Comparison of Outcomes Between Suture Button Technique and Screw Fixation Technique in Patients With Acute Syndesmotic Diastasis: a Meta-analysis of Randomized Controlled Trials." Foot & ankle orthopaedics 6(4): 24730114211061405.
	BACKGROUND: Our aim was to compare the outcome between suture button (SB) stabilization and syndesmotic screw fixation (SF) in patients with acute syndesmotic diastasis. METHODS: A systematic literature search up to June 30, 2021, was performed to identify randomized controlled trials (RCTs) comparing outcomes of SB with SF techniques in patients with acute syndesmotic diastasis. We calculated mean differences for continuous outcomes, using the Hartung‐Knapp‐Sidik‐Jonkman method, and odds ratio for dichotomous outcomes, using the Mantel‐Haenszel method. RESULTS: Eight RCTs involving 569 patients met the inclusion criteria, 1 RCT with level I evidence, and 7 RCTs with level II evidence. The meta‐analysis showed that the SB technique had a higher AOFAS score <6 months and 12 months postoperatively (MD = 4.74, 95% CI 1.68‐7.80, P = .01; and MD = 5.42, 95% CI 1.50‐9.33, P = .02) and reduced the risk of implant irritation (OR = 0.31, 95% CI 0.11‐0.89, P = .03), implant failure (OR = 0.06, 95% CI 0.02‐0.23, P < .01), and reoperation (OR = 0.43, 95% CI 0.22‐0.83, P = .01). The 2 approaches did not differ in further functional outcomes or postoperative complications. CONCLUSION: Because functional outcomes showed no relevant difference between both SB and SF, the advantage of SB appears to be in the lower risk for postoperative complications. The SB technique led to fewer cases of implant irritation, implant failure, and reoperation compared with SF. LEVEL OF EVIDENCE: Level I, meta‐analysis of RCTs.

Ramírez-García, I., et al. (2021). "Patient-reported outcomes in the setting of a randomized control trial on the efficacy of transcutaneous stimulation of the posterior tibial nerve compared to percutaneous stimulation in idiopathic overactive bladder syndrome." Neurourology and Urodynamics 40(1): 295‐302.
	Aim: To compare the efficacy of transcutaneous tibial nerve stimulation (TTNS) with percutaneous tibial nerve stimulation (PTNS) regarding patient‐reported outcomes measures, specifically quality‐of‐life (QoL) improvement and patient's treatment benefit, on symptoms associated with overactive bladder (OAB). Methods: Patients with refractory OAB symptoms and detrusor overactivity were randomized to receive TTNS or PTNS for 12 weeks. Data from self‐report OAB questionnaire short form (q‐SF) and incontinence (I)‐QoL questionnaires were collected pretreatment and at Weeks 6 and 12. Patients’ self‐perceived benefits on symptoms (treatment benefit scale, TBS) were also gathered. Mean change in scores within and between groups were estimated. Results: Sixty‐eight adult patients (67.6% women) were included in the intention to treat analysis. Of those, 61 completed all questionnaires and were analyzed as per protocol. Statistically significant improvements in OAB‐q‐SF and I‐QoL between baseline and end‐of‐treatment scores were observed in both TTNS and PTNS groups (p <.001), being the differences much higher than the minimal important difference in both questionnaires. The scores of the OAB‐q‐SF scales (symptoms bother and health‐related QoL) showed no statistically significant differences between the two groups. Similarly, the differences regarding the I‐QoL questionnaire were statistically nonsignificant either (p =.607). When assessing the treatment benefit on symptoms, TBS responses between groups showed no statistical differences. Conclusion: A significant improvement of QoL was observed in both TTNS and PTNS groups. However, no patient‐reported outcomes measures scores support a difference between the two groups. Therefore, these findings along with TTNS ease of application and less invasiveness may lead to an increased indication of this technique for OAB.

Rancourt Kate, M., et al. (2022). "Sexual communication mediates cognitive-behavioral couple therapy outcomes: A randomized clinical trial for provoked vestibulodynia." Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) 36(7): 1073-1083.
	Provoked vestibulodynia (PVD) is a chronic vulvovaginal pain condition affecting 8%-10% of women and is associated with negative sexual sequalae. Our randomized clinical trial comparing cognitive-behavioral couple therapy (CBCT) to a medical intervention (lidocaine) found that both treatments improved affected women's pain and both affected women's and partners' sexual outcomes, with CBCT demonstrating more benefits (Bergeron et al., 2021). The goal of this study was to examine two putative mediators of CBCT's treatment effects: collaborative and negative sexual communication patterns (SCPs). Women with PVD and their partners were randomly assigned to 12 weeks of CBCT ( N = 53) or lidocaine ( N = 55). Outcome measures (sexual satisfaction, function, and distress) were collected at pre-treatment, post-treatment, and 6-month follow-up, and in-treatment measures of the mediators were taken at Weeks 1, 4, 8, and 12 of treatment. Results showed that affected women's reports of improving collaborative communication mediated the effect of CBCT, but not lidocaine, on post-treatment sexual satisfaction (women with PVD and partners), sexual function (women with PVD), and sexual distress (women with PVD). For partners, collaborative communication improved equally in both treatments. Given that there were no differences in negative SCPs between the CBCT and lidocaine conditions, it was not possible to examine negative communication as a potential mediator. From the perspective of women with PVD, CBCT helped couples communicate about their sexual problems in more collaborative ways, which was in turn beneficial for improving the sexual well-being of both members of the couple. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Rane, A. and S. Pohlman (2021). "PMD2 Laparoscopic Radiofrequency Ablation VS Laparoscopic Myomectomy in the Treatment of Symptomatic Uterine Leiomyomas: A Meta-Analysis of Randomized Controlled Trials." Value Health 24: S123-None.
	
Ranger Tom, A., et al. (2021). "Hormone replacement therapy and cancer survival: a longitudinal cohort study: protocol paper." BMJ Open 11(8): e046701.
	Introduction: Hormone replacement therapy (HRT) can help women experiencing menopausal symptoms, but usage has declined due to uncertainty around risks of cancer and some cardiovascular diseases (CVD). Moreover, improved cancer survival rates mean that more women who survive cancer go on to experience menopausal symptoms. Understanding these relationships is important so that women and their clinicians can make informed decisions around the risks and benefits of HRT. This study's primary aim is to determine the association between HRT use after cancer diagnosis and the risk of cancer-specific mortality. The secondary aims are to investigate the risks of HRT on subsequent cancer, all-cause mortality and CVD.; Methods and Analysis: We will conduct a population-based longitudinal cohort study of 18-79 year-old women diagnosed with cancer between 1998 and 2020, using the QResearch database. The main exposure is HRT use, categorised based on compound, dose and route of administration, and modelled as a time-varying covariate. Analysis of HRT use precancer and postcancer diagnosis will be conducted separately. The primary outcome is cancer-specific mortality, which will be stratified by cancer site. Secondary outcomes include subsequent cancer diagnosis, CVD (including venous thrombo-embolism) and all-cause mortality. Adjustment will be made for key confounders such as age, body mass index, ethnicity, deprivation index, comorbidities, and cancer grade, stage and treatment. Statistical analysis will include descriptive statistics and Cox proportional hazards models to calculate HRs and 95% CIs.; Ethics and Dissemination: Ethical approval for this project was obtained from the QResearch Scientific Committee (Ref: OX24, project title 'Use of hormone replacement therapy and survival from cancer'). This project has been, and will continue to be, supported by patient and public involvement panels. We intend to the submit the findings for peer-reviewed publication in an academic journal and disseminate them to the public through Cancer Research UK.; Competing Interests: Competing interests: JH-C is an unpaid director of the Qresearch database (partnership between the University of Oxford and EMIS, commercial supplier of GP computer systems). She is shareholder and former director of ClinRisk Ltd outside the submitted work. PST reports consulting with AstraZeneca and Duke-NUS outside the submitted work. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Ranisavljevic, N., et al. (2019). "Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review." Journal of Assisted Reproduction and Genetics 36(11): 2217-2231.
	Human endometrium has a key role in implantation process. The measurement of endometrial thickness is the most commonly used in clinical practice. Managing patients with thin endometrium still represents a major challenge for clinicians. The objective of this systematic review was to investigate all available interventions to improve endometrial thickness (EMT) in women with history of thin endometrium undergoing fresh or frozen-thawed embryo transfers (ET). We performed a comprehensive search of relevant studies from January 1978 to February 2018. The different strategies were categorized as hormonal, vascular, and growth factor approaches and specifically analyzed according to the type of ET. Thirty-one studies were included. Overall, quality of the evidence ranged from very low to moderate, with only few randomized controlled trials that support the use of either GnRH analogues in fresh ET or sildenafil in frozen ET for enhancing endometrial growth. Besides, intensified estradiol administration is a common approach that might improve EMT in frozen ET. The present review evidences the paucity of reliable data regarding the efficiency of different interventions aiming at increasing EMT before fresh or frozen-thawed ET. Robust and high-quality randomized controlled trials are still needed before guidelines can be established.

Ranka, O., et al. (2022). "EFFECTS OF EXERCISES FOR STRENGTHENING PELVIC FLOOR MUSCLES IN PREGNANT WOMEN." Medicinski Casopis 56(3): 107-112.
	The pelvic floor is a complex network formed by deep and superficial muscle structures, the vaginal wall and fascia that provides support to the pelvic organs and maintains continence. Changes in the urinary and muscular system during pregnancy cause pelvic floor muscle dysfunction and stress urinary incontinence (SUI). By strengthening these muscles, the symptoms of incontinence can be alleviated. The aim of this paper is to prove the effectiveness of pelvic floor muscle strengthening exercises in the prevention and treatment of urinary incontinence in pregnant women through a systematic review of the available literature. Using the keywords "pelvic floor exercises", "urinary incontinence", "pregnancy", "prevention", "prenatal period" and "postnatal period", three independent authors searched database search engines (PubMed, Physiotherapy Evidence Database and Cochrane Library) for relevant articles from October 2021 to April 2022 using the predetermined criteria, and selected potential papers. The search resulted in 75 works. The papers older than five years, not available in full text, or not written in English were excluded. Ten works that met the criteria were included in the research. The selection was made by using the Jovell and Navarro-Rubio classification of study designs. The classified papers have provided evidence of the importance of prenatal exercises in improving pelvic floor muscle contractility. Structured, supervised training increases the strength of these muscles, reduces urinary symptoms and incontinence. The exercises to strengthen the muscles of the pelvic floor prevent incontinence, reduce the intensity of symptoms and improve the quality of life during pregnancy and postpartum. Health experts have a significant contribution in the education of pregnant women. It is a priority to develop standardized educational programs through which these exercises will be effectively applied.Copyright © 2022, Serbian Medical Society. All rights reserved.

Rao Elizabeth, M., et al. (2023). "Surgical treatment of early-stage vulvar squamous cell carcinomas: a systematic review of guidelines for dermatologic surgeons." International journal of women's dermatology 9(3): e104.
	Early-stage vSCC is considered appropriate for treatment by Mohs micrographic surgery (MMS), with advantageous intraoperative margin assessment.2 In gynecology, early-stage tumors are treated with wide local excision, radical vulvectomy, lymph node dissection, and adjuvant chemoradiation for specific cases. Understanding gynecologic-oncology recommendations aids in recognizing when to escalate treatment to provide optimal care. We provide a systematic review of the most up-to-date society guidelines for the treatment of early-stage vSCC to inform dermatologic surgeons caring for these patients. A PubMed and Google Scholar search was performed using the terms “Vulvar” AND “Squamous cell carcinoma” AND “treatment” AND “guidelines” using Preferred Reporting Systems for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of 341 initial search results, 18 articles remained after screening for updated versions and English language; of these, 13 related to surgical treatment of early-stage vulvar carcinomas and were included (Fig. 1).

Rao, M., et al. (2023). "A review analysis of exercise training regimes among females with polycystic ovary syndrome." JPMA. The Journal of the Pakistan Medical Association 73(3): 589-602.
	Objective: The current systematic review was planned to provide quality assessment of different exercise regimes and their outcomes on the symptoms of polycystic ovary syndrome, and to see if one exercise regime was better than the rest.; Methods: Search was conducted on PubMed and Google Scholar databases for studies published between 2001 and 2021 whose full text was available. The search yielded 28 studies that were reviewed.; Results: The current evidence suggests that exercise regimes, such as high-intensity interval training, progressive resistance training, aerobic exercises, and yoga may improve polycystic ovary syndrome conditions. This is accomplished through treating associated risk factors, like body morphology, insulin resistance, hyperandrogenism, lipid profile, reproductive hormones, menstrual cycle, and quality of life.; Conclusions: Exercise regimes improves several symptoms of polycystic ovary syndrome. However, selecting a specific exercise regime over others as the standardised treatment protocol remained inconclusive.

Raouf, S., et al. (2019). "Real-world use of bevacizumab in metastatic colorectal, metastatic breast, advanced ovarian and cervical cancer: a systematic literature review." Future oncology (London, England) 15(5): 543-561.
	Aim: This review aims to assist physicians and payers in assessing the efficacy and safety of bevacizumab in real-world clinical practice by identifying evidence on the comparative effectiveness and safety of bevacizumab in its most frequent indications. Materials & methods: In a systematic review of the published literature, electronic databases (Embase ® , MEDLINE ® and the Cochrane Library) were searched in May 2016 and updated in January 2017; 20 scientific congresses were searched in 2014-2017.; Results: Of 61 included publications, 49, eight, four and 0 concerned metastatic colorectal cancer, metastatic breast cancer, advanced ovarian cancer and cervical cancer, respectively. Fifteen publications (metastatic colorectal cancer) reported on factors predictive of response to therapy.; Conclusion: Effectiveness findings from real-world studies broadly supported results from registration studies.

Rapisarda Agnese Maria, C., et al. (2023). Lacticaseibacillus Rhamnosus CA15 (DSM 33960) Strain as a New Driver in Restoring the Normal Vaginal Microbiota.
	No Results Available Dietary Supplement: Lacticaseibacillus rhamnosus CA15 (DSM 33960) probiotic strain|Dietary Supplement: placebo Microbiota|Symptomatology|Sign|Well-being Female Not Applicable 200 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment 113/2022/PO March 30, 2024

Raquel, L.-R. and G.-M. Ángela (2022). "Efficacy of electrotherapy and manual therapy in the treatment of primary dysmenorrhea."
	
Raquel, L.-R. and P.-Á. Claudia (2023). "Effectiveness of physiotherapy treatment for pelvic floor dysfunctions following gynecologic cancer."
	
Rashidi Fakari, F., et al. (2023). "Effect of Hypnosis in Adolescents: A Narrative Review." Journal of Pediatrics Review 11(1): 25-36.
	Background: More than half of reproductive-age women experience dysmenorrhea, which can reduce their quality of life. The treatment options for dysmenorrhea are medications and alternative therapies. The tendency to use alternative therapies, such as hypnotherapy has increased.&nbsp; Objectives: This study aimed to carry out a narrative review to evaluate the effect ...

Rashidian, P. (2024). "An update on oncofertility in prepubertal females." Journal of Gynecology Obstetrics and Human Reproduction 53(4): 102742.
	Cancer is a life-threatening event for pediatric patients. Treatment advancements in pediatric cancer have improved prognosis, but some of these treatments have gonadotoxic potential and may affect fertility in different ways. Due to the growing interest of the research community in the life prospects of young cancer survivors, there has been a demand to intersect reproductive medicine and oncology, which is referred to as "oncofertility". There are various fertility preservation options according to gender and pubertal status, and shared decisions must take place at the time of diagnosis. This study aims to provide a critical review of current and emerging strategies for preserving and restoring fertility in prepubertal females, ranging from established methods to experimental approaches that can be offered before, during, and after anticancer therapies. Additionally, the author aims to review how clinicians' awareness of oncofertility options and the latest advancements in this field, timely referral, and proper consultations with patients and their families are vital in addressing their concerns, providing emotional support, and guiding them through the decision-making process, as well as potential barriers that may hinder the fertility preservation process.Copyright © 2024 Elsevier Masson SAS

Ray-Coquard, I., et al. (2023). "Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial." Annals of oncology : official journal of the European Society for Medical Oncology 34(8): 681-692.
	Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status.; Patients and Methods: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis.; Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms.; Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.; Competing Interests: Disclosure IRC reports honoraria (personal) from AbbVie, Agenus, Advaxis, Bristol Myers Squibb (BMS), PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD), Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis; honoraria (institution) from GSK, MSD, Roche, and BMS; advisory/consulting fees from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis; research grant/funding (self) from MSD, Roche, and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca, and Merck Sereno; and travel support from Roche, AstraZeneca, and GSK. AL reports grants from AstraZeneca and Sanofi; consulting fees from Seattle Genetics; honoraria/reimbursement and advisory board fees from AstraZeneca; advisory board fees or continuing medical education from Ability Pharma, Biocad, Clovis Oncology, GSK, Medscape, Merck Serono, MSD, TouchCongress, and Zentalis; support for attending meetings and/or travel from AstraZeneca, Clovis Oncology, GSK, and Roche; and participation on a data safety monitoring board or advisory board for ARIEL4 and TROPHIMMUNE. SP reports honoraria from AstraZeneca, Roche, MSD, Pfizer, Tesaro, Clovis Oncology, GSK, and PharmaMar; and research funding (institution) from Roche, MSD, AstraZeneca, and Pfizer. AGM reports advisory/consultancy fees (personal) from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Eisai, Genmab, GSK, Hedera Dx, Illumina, ImmunoGen, MSD, Macrogenics, Mersana, Novartis, Oncoinvent, PharmaMar, Roche, Regeneron, Sotio, and Sutro; speaker bureau fees (personal) from AstraZeneca, Roche, GSK, MSD, Novocure, Takeda, Zai Lab, and Clovis; research g ant/funding (institution) from Roche, Novartis, GSK, and Aravive; and steering committee member (personal) for MSD. CM reports honoraria/consulting fees (personal) from Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, and Seagen; participation on an advisory board from Roche, Novartis, Amgen, MSD, PharmaMar, AstraZeneca, GSK, and Seagen; and travel expenses from Roche and AstraZeneca. SN reports honoraria (self) from AstraZeneca, Chugai, Mochida, MSD, Takeda, and Terumo; and research grant (self) from AstraZeneca. IV reports consulting fees from Agenus, Akesobio, AstraZeneca, BMS, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Seagen, Sotio, Verastem Oncology, and Zentalis; contracted research funding (via KULeuven) from Oncoinvent AS; corporate sponsored research funding from Amgen and Roche; and accommodation and travel expenses from Karyopharm. NC reports research grants from AstraZeneca, PharmaMar, and Roche; honoraria for lectures from AstraZeneca, Tesaro, Novartis, Clovis Oncology, MSD, GSK, and Eisai; honoraria for advisory boards from Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GSK, Tesaro, Pfizer, BIOCAD, ImmunoGen, Mersana Therapeutics, Eisai, and OncXerna Therapeutics; and is a steering committee member on ESMO clinical guidelines and a scientific committee chair for Acto Onlus. JM reports honoraria from AstraZeneca and GSK. FS reports honoraria from AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology; and institutional financial support from Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. JS reports grants or contracts from Roche Pharma, AstraZeneca, Bayer, Clovis, GSK, Lilly, Tesaro, consulting fees from Tesaro, Merck, Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharma, GSK, MSD, Eisai, Novocure, Oncoinvent, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Tesaro, GSK, PharmaMar, AstraZeneca, Clovis, Bayer, Roche, PharmaMar, Vifor Pharma, Hexal AG, Novartis Pharma. DL reports consultancy fees (personal) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, Novartis, and Seagen; membership on an advisory board (personal) from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; research funding (institutional) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; and travel support from Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GSK. EMGA reports consulting fees from AstraZeneca–MSD, Clovis Oncology, GSK–Tesaro, PharmaMar, and Roche; speaker bureau/expert testimony honorarium from AstraZeneca–MSD, PharmaMar, Roche, GSK–Tesaro, and Clovis Oncology; and travel support from Roche, GSK–Tesaro, and Baxter. GB reports consulting or advisory board roles for AstraZeneca, Roche, and GSK; and has received funding for medical conferences from AstraZeneca, Roche, and GSK. CLP reports advisory/consultancy honoraria from Pfizer, AstraZeneca, Roche, and Daiichi–Sanko; and other travel/accommodation/medical congress expenses from Roche, Novartis, Pfizer, Pierre Fabre, and MSD. PB reports honoraria from Roche, AstraZeneca, and GSK; and congress and travel support from GSK and PharmaMar. AL reports advisory board fees from AstraZeneca, MSD, and Tesaro; speaker honoraria from Clovis Oncology and Roche; and participation in a medical congress for Novartis, Pfizer, MSD, Lilly, and Roche. AB reports honoraria for lectures and advisory boards from AstraZeneca, Roche, and Tesaro. JM reports advisory board fees (personal) from Daiichi Sankyo, Gilead, and Eli Lilly; and non-financial traveling facilities from Pfizer. AEB reports advisory board fees from AstraZeneca, MSD, and GSK; speaker honoraria from AstraZeneca and Olympus; and participation in a medical congress for PharmaMar and AstraZeneca. MR reports advis ry board fees (personal) from AstraZeneca, GSK, and Immunocore; advisory board fees and research grant (personal/institution) from MSD; and research grant (institution) from BMS. TWPS reports honoraria (advisory role, expert testimony and lectures, participation in clinical trials, other financial relationships, e.g. travel) from AstraZeneca, Daiichi-Sankyo, Exact Sciences, Gilead, GSK, Lilly, MSD, NCO, Novartis, Pfizer, Roche, and Seagen. CD reports participation on a data safety monitoring board or advisory board for MSD, Eisai, and AstraZeneca. DD reports consulting or advisory roles (personal) for AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; travel expenses from AstraZeneca; and honoraria from Roche, AstraZeneca, GSK/Tesaro, MSD, Intuitive Surgical, and KLS Martin. BY reports consulting fees (personal) from MSD, AstraZeneca, GSK–Tesaro, Bayer, Roche–Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, and Myriad. EPL reports lecture fees, speaker’s bureau fees, and travel support from AstraZeneca, Tesaro, and Roche; lecture fees from Clovis Oncology, Incyte, and Pfizer; and is employed by ARCAGY Research. PH reports honoraria from AstraZeneca, Roche, Clovis Oncology, Stryker, MSD Oncology, Zai Lab, Lilly, Sotio, Eisai, and GSK; consulting/advisory roles from AstraZeneca, Roche, Tesaro, Merck, GSK, Clovis Oncology, and Immunogen; and research funding (institution) from AstraZeneca, Roche, Genmab, GSK, Immunogen, and Clovis Oncology. All other authors have declared no conflicts of interest. (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Razzak Md, A., et al. (2023). "Digital health interventions for cervical cancer care: A systematic review and future research opportunities." PloS One 18(12): e0296015.
	Background: Cervical cancer is a malignancy among women worldwide, which is responsible for innumerable deaths every year. The primary objective of this review study is to offer a comprehensive and synthesized overview of the existing literature concerning digital interventions in cervical cancer care. As such, we aim to uncover prevalent research gaps and highlight prospective avenues for future investigations.; Methods: This study adopted a Systematic Literature Review (SLR) methodology where a total of 26 articles were reviewed from an initial set of 1110 articles following an inclusion-exclusion criterion.; Results: The review highlights a deficiency in existing studies that address awareness dissemination, screening facilitation, and treatment provision for cervical cancer. The review also reveals future research opportunities like explore innovative approaches using emerging technologies to enhance awareness campaigns and treatment accessibility, consider diverse study contexts, develop sophisticated machine learning models for screening, incorporate additional features in machine learning research, investigate the impact of treatments across different stages of cervical cancer, and create more user-friendly applications for cervical cancer care.; Conclusions: The findings of this study can contribute to mitigating the adverse effects of cervical cancer and improving patient outcomes. It also highlights the untapped potential of Artificial Intelligence and Machine Learning, which could significantly impact our society.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Razzak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Razzi, S., et al. (2022). "CARBOPLATIN FOLLOWED BY OLAPARIB VERSUS BEVACIZUMAB IN MANTEINANCE THERAPY IN ELDERLY PATIETS WHIT ADVANCED OVARIAN CANCER." Tumori 108(4 Supplement): 106-107.
	Background: Poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations. The aim of our study was to assess the efficacy and tolerability of Carboplatin in single agent therapy, followed by olaparib maintenance monotherapy, versus manteinance therapy bevacizumab in elderly patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer according to BRCA status. Method(s): In our retrospective study, old patients (median age 80) with platinum-sensitive, recurrent, high-grade serous ovarian cancer received carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1)followed by olaparib monotherapy (400 mg capsules twice daily, given continuously) or Bevacizumab 15 mg/kv ev on day 1 every 21 days until progression The primary endpoint was progression- free survival. Finding(s): Between Feb 17 and July 30, 2021, 17 patients were eligible and were assigned to the two treatment groups (5 to the olaparib group and 12 to the bevacizumab group). BRCA mutation status was known for all patients (either at baseline or determined retrospectively): 5 of 17 had a BRCA mutation Progression-free survival was significantly longer in the olaparib group (median 24.2 months [95% CI 9.7-15.0]) than in the bevacizumab group (median 9.6 months [95% CI 9.1-9.7) (HR 0.51 [95% CI 0.34-0.77]; p=0.0012), especially in patients with BRCA mutations (HR 0.21 [0.08-0.55]; p=0.0015). Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. Interpretation(s): Carboplatin in monotherapy followed by olaparib in manteinance therapy significantly improved progression-free survival versus bevacizumabl plus carboplatin alone, with the greatest clinical benefit in BRCAmutated patients, and had an acceptable and manageable toxicity profile.

Rebeca, A.-C. and C.-L. Marta (2022). "Benefits of physical therapy in improving quality of life and pain associated with endometriosis: systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Rebecca, G., et al. (2021). "Secondary cytoreductive surgery for recurrent low-grade serous ovarian cancer: A systematic review." PROSPERO International prospective register of systematic reviews.
	
Rebouças Karinne, F., et al. (2019). "Treatment of bacterial vaginosis before 28 weeks of pregnancy to reduce the incidence of preterm labor." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 146(3): 271-276.
	Background: Controversy exists regarding the benefits of treating bacterial vaginosis (BV) during pregnancy to reduce the incidence of preterm labor (PTL).; Objectives: To evaluate whether treatment of BV with vaginal clindamycin or oral metronidazole before 28 weeks of pregnancy reduces PTL incidence.; Search Strategy: PubMed, Scopus, Web of Science, Science Direct, CENTRAL, and SciELO databases were searched until December 30, 2017. Search terms included "bacterial vaginosis" and "preterm labor." No language restrictions were applied.; Selection Criteria: Randomized clinical trials that evaluated treatment of BV with clindamycin or metronidazole to reduce PTL incidence.; Data Collection and Analysis: The risk of PTL was evaluated by the odds ratio (OR) and 95% confidence interval (CI). Dichotomous data from each study were combined for meta-analysis using the Mantel-Haenszel model.; Main Results: Nine reports were included in the systematic review, with eight reports included in the meta-analysis. No reduction in the incidence of PTL was found for either metronidazole (OR 0.94, 95% CI 0.71-1.25) or clindamycin (OR 1.01, 95% CI 0.75-1.36).; Conclusions: Use of oral metronidazole or vaginal clindamycin to treat BV before 28 weeks of pregnancy did not reduce the incidence of PTL. PROSPERO registration: CRD42018086173. (© 2019 International Federation of Gynecology and Obstetrics.)

Rechberger, E., et al. (2022). "Femistina versus Canephron as a prevention of urinary tract infections after midurethral sling surgery - Non-inferiority study." European Journal of Obstetrics and Gynecology and Reproductive Biology 277: 71-76.
	Objective: Urinary tract infection (UTI) is relatively common post-operative complication following midurethral sling placement (MUS), even in cases where intraoperative antibiotic prophylaxis was given. The primary aim of this study was to investigate the non-inferiority of Femistina as compared with Canephron in reducing symptomatic UTI in first six months following surgery. Study design: A sample size of 144 patients per group was established, to provide at least 90% power to demonstrate the non-inferiority of phytodrug Femistina versus Canephron as a prevention of post-MUS urinary tract infection. Result(s): Women suffering from stress urinary incontinence and mixed urinary incontinence (MUI) with predominant SUI symptoms as confirmed by urodymamics (n = 320) were randomized in a 1:1 ratio to Femistina (40 mg, oral, twice daily for 20 days) or Canephron (3 x 5 ml taken orally-three times daily for 4 weeks). Both groups were homogenous for age, type of operation (only TOT outside-in) and severity of illness as indicated by ICIQ-SF questionnaire. We found that symptoms of UTI were significantly lower in patients receiving Femistina. During first 6 months after surgery UTI was confirmed in only 10 patients receiving Femistina (6,25%) when compared to 25 (15,63%) subjects receiving Canephron, p < 0.007. Conclusion(s): Femistina is not inferior to Canephron in preventing lower urinary tract infection after midurethral sling surgery.Copyright © 2022

Reechashree, D., et al. (2021). "Effect of Myo-inositol vs Metformin on Insulin Resistance, Ovarian Function and Androgen levels in Women With Polycystic Ovarian Syndrome- A Systematic Review and Meta-Analysis of Randomized Controlled Trials."
	
Regaud Institut, C., et al. (2023). PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer.
	No Results Available Other: Standard treatment: Control arm|Procedure: Experimental arm Disease Free Survival (DFS) defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause.|Overall survival defined by the delay between randomization and death from any cause.|Metastasis Free Survival (MFS) defined as the time from randomization until first distant relapse, or death from any cause.|Morbidity assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v 5.0).|Quality of life will evaluated by the EORTC QLQ-C-30 questionnaire. Female Phase 3 510 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 22GENF08 June 2033

Regidor, P.-A. and E. Colli (2022). "The progestin-only pills drospirenone 4 mg and desogestrel 0.075 mg as an option for the management of dysmenorrhea and mastodynia." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(11): 978-982.
	Introduction: Dysmenorrhea and mastodynia are the most common gynecologic pain causes in women of all ages and races during their reproductive life. The following study aimed to show the influence of two POP´s in the development of dysmenorrhea and mastodynia after nine months of use.; Material and Methods: A total of 858 women with 6691 drospirenone (DRSP) cycles and 332 women with 2487 desogestrel (DSG) cycles were analyzed. Women included in this study were all child-bearing potentials, at risk of pregnancy, agreeing to use only the study medication for contraception for the duration of the study medication treatment, aged 18 to 45.; Results: At screening, 168 (19.6%) of the 858 patients using DRSP and 64 (19,3%) of the DSG patients reported that they had suffered from dysmenorrhea within six cycles prior to the first visit before starting with the medication. 20,2% of the DRSP and 10,9% of the DSG group had a sever dysmenorrhea. After 9 cycles this was reduced to 0,6% and 3,1% respectively. In total, 96 women (11.2%) in the DRSP and 49 (14,8%) experienced mastodynia within six cycles before the screening. Of these 91.6% in the DRSP group and 91,8% in the DSG group had no or mild mastodynoa at follow-up.; Discussion: The progestins 4 mg and desogestrel 0,075 mg showed a marked effect in the non-contraceptive aspects of dysmenorrhea and mastodynia so that new possibilities are opened for these two benign gynecological diseases. Future studies must reaffirm these first data.

Regina University, o., et al. (2023). Testing an Evidence-Based Self-Help Program for Infertility-Related Distress in Women.
	No Results Available Behavioral: Coping with Infertility Self-Help Program Fertility Quality of Life (FertiQoL) Score, at Mid-Treatment, Post-Treatment and Biweekly for 16 Weeks Post-Treatment|Mean Infertility-Related Distress Scores on the Copenhagen Multi-Centre Psychosocial Infertility - Fertility Problem Stress Scales (COMPI-FPSS), at Post-Treatment and Biweekly for 16 Weeks Post-Treatment|Mean Depression Scores on the Patient Health Questionnaire-9 (PHQ-9), at Post-Treatment and Biweekly for 16 Weeks Post-Treatment|Mean Anxiety Scores on the Generalized Anxiety Disorder-7 (GAD-7), at Post-Treatment and Biweekly for 16 Weeks Post-Treatment|Mean Relationship Quality on the Relationship Assessment Scale (RAS), at Post-Treatment and Biweekly for 16 Weeks Post-Treatment|Occurrence of Mood and Anxiety Disorders at Baseline, Post-Treatment, and 16 Weeks After Treatment Female Not Applicable 170 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment REB #2023-210|DCO150GP|6447 September 2025

Region Vastra, G. and G. University (2021). Progesterone as Luteal Support in Frozen IVF Natural Cycles.
	No Results Available Drug: Progesterone vaginal tablet Number of participants with live birth|Number of participants with biochemical pregnancy|Number of participants with clinical pregnancy|Number of participants with ongoing pregnancy|Number of participants with miscarriage|Number of participants with ectopic pregnancy|Number of participants with termination of pregnancy|Birth weight|Gestational age at delivery|Preterm birth|Very preterm birth|Low birth weight|Very low birth weight|Stillbirth|Perinatal death|Number of children with birth defects|Number of children admitted to Neonatal Intensive Care Unit (NICU)|Number of participants with hypertensive disorders of pregnancy|Number of participants with placenta previa|Number of participants with placenta abruption|Number of participants with postpartum hemorrhage|Number of participants with Cesarean section|Number of participants with thromboembolic events|Maternal mortality|Number of participants with treatment related side effects|Number of participants with adverse events|Cost effectiveness Female Phase 4 1800 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2020-005552-38 June 30, 2024

Reid, K. J., et al. (2021). "Effects of manipulating body temperature on sleep in postmenopausal women." Sleep medicine 81: 109‐115.
	Study objectives: A decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post‐menopausal women. Methods: Twenty‐four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single‐blind, counterbalanced, cross‐over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8‐h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively. Results: In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5–1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001). Conclusions: The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women.

Reijntjes, B., et al. (2022). "Recurrence and survival after laparoscopy versus laparotomy without lymphadenectomy in early-stage endometrial cancer: Long-term outcomes of a randomised trial." Gynecologic Oncology 164(2): 265-270.
	Background: Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively.; Methods: Follow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined.; Results: In total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31-1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30-1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23-1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable.; Conclusion: Disease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer.; Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Reis, B. M., et al. (2021). "Intravaginal electrical stimulation associated with pelvic floor muscle training for women with stress urinary incontinence: study protocol for a randomized controlled trial with economic evaluation." Trials 22(1): 823.
	Introduction: Pelvic floor muscle training (PFMT) exercises and neuromuscular electrical stimulation (NMES) are described as conservative interventions to prevent or treat female stress urinary incontinence (SUI). However, it has not been described yet the effect of PFMT associated to intravaginal NMES which evaluated the cost-effectiveness and cost-utility of treating. Aim(s): To evaluate the effects of intravaginal NMES associated with the PFMT protocol on urinary loss and quality of life in women with SUI and to evaluate the cost-effectiveness and cost-utility and pelvic floor muscle in women with SUI. Method(s): Randomized controlled trial study with economic evaluation. Inclusion criteria are woman (biological), aged >= 18 years old and with a report of SUI >= once/week. Exclusion criteria are presence of vaginal or urinary infection, virginity, being in the gestational or puerperium period, or neurological disease. Participants will undergo physical therapy assessment and intervention: anamnesis, pelvic floor muscle assessment by vaginal palpation and manometry (PeritronTM), questionnaires (Short-Form 6 Dimensions-Brazil (SF-6D), King's Health Questionnaire (KHQ) and King's Health Questionnaire for Scoring Algorithm), health costs, and voiding diary. Participants will be randomly allocated into 3 groups: CG (control group), IG 1 (intervention group 1, PFMT), and IG2 (intervention group 2, PFMT + NMES). The statistical analysis will be performed by intention to treat, and multivariate analysis of mixed effects will be used to compare outcomes. Effect size measurements will be calculated and will be provided by Cohen's d test. A significance level of 5% will be adopted. Additionally, the incremental cost-effectiveness and incremental cost-utility ratios will be used. Discussion(s): This protocol can corroborate with the literature in order to identify the effect of techniques, based on the possibility of confirming the hypothesis that the NMES associated with PFMT performed concurrently will be the best treatment option; considering the effectiveness, cost-effectiveness, and cost-utility analysis, it will be used as an option for optimization of the treatment of SUI. Trial registration: Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-6gtzg4. Registered on September 3, 2019.Copyright © 2021, The Author(s).

Reiser, E., et al. (2024). "Female cancer survivors: sexual function, psychological distress, and remaining fertility." Journal of Assisted Reproduction and Genetics.
	Purpose: Improved survivorship in cancer patients leads to new challenging issues including potential impairment of quality of life, sexual function, and fertility. The aim of this study was to assess sexual dysfunction (SD) and psychological distress in female cancer survivors who underwent fertility preservation in the past in comparison to reviewed healthy control data from other published studies. Additionally, our focus was on the difference in SD between women with current desire to get pregnant and already completed family planning. Method(s): In this prospective study, 53 female cancer survivors who underwent fertility preservation at time of cancer diagnosis between 2010 and 2020 were invited to a gynecological exam, laboratory assessment, and two questionnaires (Female Sexual Function Index (FSFI) and Hospital anxiety and depression scale (HADS)) in 2022. These scores were compared to results in the literature of healthy controls and depending on anti-Mullerian-hormone (AMH) levels, current desire to have a child, and age. Result(s): After a mean follow-up time of 70 +/- 50 months, SD was detected in 60.4% (n = 32) of the 53 included patients. Normal results regarding HADS-D/anxiety and HADS-D/depression were found in 88.7% and 94.3% of patients, respectively. At time of follow-up, 69.9% (n = 40) regained regular menstrual cycles, 52.6% (n = 20) < 40 years showed a diminished ovarian reserve with AMH levels < 1.1 ng/ml and 28.3% (n = 15) suffered from infertility. Conclusion(s): Female cancer survivors may be at risk for SD. Cancer patients should be informed about possible sexual dysfunction already at the start of cancer treatment and during follow-up. In addition, contraception needs to be addressed if regular cycles occur as more than two-thirds of the women regained regular menstrual cycles.Copyright © The Author(s) 2024.

Reiser, E., et al. (2022). "Non-Hormonal Treatment Options for Regulation of Menstrual Cycle in Adolescents with PCOS." Journal of Clinical Medicine 12(1).
	Menstrual irregularities are one of the main clinical symptoms caused by polycystic ovary syndrome (PCOS). Pharmacological treatment options for non-fertility indications to restore menstrual frequency play an important role in the management of PCOS. Oral contraceptive pills are commonly prescribed for adolescents with menstrual irregularities, however, when contraindicated or poorly tolerated, further pharmacological therapy is required. This systematic literature research aims to provide an overview concerning the effects of non-hormonal pharmacological treatment options on menstrual irregularities in adolescents suffering from PCOS. A systematic literature search in PubMed, Cochrane, Embase, Bio-SISS and Web of Science was performed, including literature from January 1998 to September 2022, using specific keywords in order to find related studies. n = 265 studies were identified of which n = 164 were eligible for further evaluation. Only four placebo-controlled studies were identified, with diverging inclusion and exclusion criteria. Available data on specific non-hormonal off-label use medication primarily consisted of metformin, Glucagon-like peptide 1 receptor agonists, thiazolidinediones, anti-androgen agents (spironolactone, finasteride, flutamide) and supplements (chromium picolinate, myo-inositol). However, only a few have partly pointed out beneficial effects on improving menstrual frequency in patients diagnosed with PCOS. In summary, metformin in dosages of 1500-2550 g/day, GLP-1-analogues and supplements were effective in regulation of menstrual cycles in adolescents diagnosed with PCOS. Menstrual frequency in adolescents with PCOS is essential to prevent hypoestrogenism with long-term consequences. In this context, MET is the most effective and cost- efficient in overweight adolescent girls, also showing beneficial effects in the regulation of insulin sensitivity, especially if COCs are contraindicated or not well-tolerated. Further studies are needed to evaluate therapies in lean and normal-weight girls with PCOS.

Reiter, A., et al. (2024). "The Effects of Long-Term Dienogest Therapy on In Vitro Fertilization Outcomes in Women with Endometriosis: A Systematic Review and Meta-Analysis." Journal of Obstetrics and Gynaecology Canada: 102339.
	Objectives: Assessing dienogest's efficacy in endometriosis patients undergoing in vitro fertilization (IVF). Data Sources: Systematic search in databases (PubMed, MEDLINE, Embase, Web of Science, Cochrane CENTRAL, Google Scholar) until 1 October 2022. Study Selections: Randomized trials and observational studies comparing extended dienogest pre-treatment, no pre-treatment, or gonadotropin-releasing hormone (GnRH) agonist pre-treatment in endometriosis-linked IVF. Outcome measures: live birth, clinical pregnancy rates, oocytes collected, miscarriage rate, gonadotropin consumption. Data Extractions and Syntheses: Two authors independently assessed eligibility. Dichotomous variables were analyzed via a random-effect model and Mantel-Haenszel method to calculate weighted estimates and 95% confidence intervals (CI). I2 statistic gauged study heterogeneity; GRADE criteria evaluated evidence quality. Conclusion(s): Out of 191 publications, five studies with 723 participants were included. Uncertainty persists on whether prolonged dienogest affects live birth (RR 1.42, 95% CI 0.29 to 6.84; 3 studies, n = 289; I2 86%) and clinical pregnancy rates (RR 1.33, 95% CI 0.31 to 5.65; 3 studies, n = 289; I2 86%) compared to conventional IVF. Moreover, uncertainty remains regarding intervention impact on live birth (RR 1.46, 95% CI 0.63 to 3.37; 1 study, n = 34) and clinical pregnancy rates (RR 1.32, 95% CI 0.78 to 2.23; 3 studies, n = 288; I2 0%) versus long-term GnRH agonist therapy before IVF. Given limited data and very low evidence quality, doubts arise about the benefits of long-term dienogest pre-treatment before conventional IVF in endometriosis patients.Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Societe des obstetriciens et gynecologues du Canada

Remie, C. M. E., et al. (2021). "Sitting less elicits metabolic responses similar to exercise and enhances insulin sensitivity in postmenopausal women." Diabetologia 64(12): 2817‐2828.
	AIMS/HYPOTHESIS: In our current society sedentary behaviour predominates in most people and is associated with the risk of developing type 2 diabetes. It has been suggested that replacing sitting time by standing and walking could be beneficial for individuals with type 2 diabetes but the underlying mechanisms are unknown and direct comparisons with exercise are lacking. Our objective was to directly compare metabolic responses of either sitting less or exercising, relative to being sedentary. METHODS: We performed a randomised, crossover intervention study in 12 overweight women who performed three well‐controlled 4 day activity regimens: (1) sitting regimen (sitting 14 h/day); (2) exercise regimen (sitting 13 h/day, exercise 1 h/day); and (3) sitting less regimen (sitting 9 h/day, standing 4 h/day and walking 3 h/day). The primary outcome was insulin sensitivity measured by a two‐step hyperinsulinaemic‐euglycaemic clamp. We additionally performed metabolomics on muscle biopsies taken before the clamp to identify changes at the molecular level. RESULTS: Replacing sitting time by standing and walking over 4 days resulted in improved peripheral insulin sensitivity, comparable with the improvement achieved by moderate‐to‐vigorous exercise. Specifically, we report a significant improvement in peripheral insulin sensitivity in the sitting less ( 13%) and the exercise regimen ( 20%), compared with the sitting regimen. Furthermore, sitting less shifted the underlying muscle metabolome towards that seen with moderate‐to‐vigorous exercise, compared with the sitting regimen. CONCLUSIONS/INTERPRETATIONS: Replacing sitting time by standing and walking is an attractive alternative to moderate‐to‐vigorous exercise for improving metabolic health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03912922.

Ren, N., et al. (2022). "Exploring the Pharmacological Mechanism of the Effective Chinese Medicines Against Gynecological Cancer Based on Meta-Analysis Combined With Network Pharmacology Analysis." Frontiers in Oncology 12: 817772.
	This meta-analysis plus network pharmacology aimed to investigate whether traditional Chinese medicine (TCM) combined with chemotherapy is associated with more beneficial efficacy data in the treatment of gynecological cancer (GC). A total of 11 randomized controlled trials (RCTs) consisting of 863 GC patients were included. Results showed a better ORR (RR: 1.42, 95% CI: 1.18-1.71; I2 = 21.4%; p = 0.282), DCR (RR: 1.13, 95% CI: 1.03-1.25; I2 = 0.0%; p = 0.492), PD (RR: 0.27, 95% CI: 0.11-0.65, p = 0.003; I2 = 0.0%, p = 0.930), and QOL (SMD: 0.85, 95% CI: 0.38-1.33, p = 0.005) and higher proportions of CD3+ T (WMD: 5.65, 95% CI: 4.23-7.08, p = 0.000; I2 = 68.3%, p = 0.004), CD4+ T (WMD: 6.97, 95% CI: 5.35-8.59, p = 0.000; I2 = 83.4%, p = 0.000), and the CD4+/CD8+ T ratio (WMD: 0.32, 95% CI: 0.23-0.42, p = 0.000; I2 = 78.0%, p = 0.000). The number of adverse events (AEs) was significantly lower in the TCM + chemotherapy group. The active components and targets of 19 high-frequency Chinese medicines obtained from the meta-analysis were screened and explored in network pharmacology analysis. Also, a regulatory network of active components and targets, a core network and key genes, a diagram of protein interaction, network topology analysis, and gene body GO function and KEGG pathway enrichment analysis were performed. A total of 120 active components were identified. NPM1 and HSPA8 are the most critical target proteins in the core network of protein interaction. HSP90AA1 is the most important target protein in the TCM group. KEGG enrichment analysis showed that it was highly significant in the lipid and atherosclerotic pathways. Therefore, moderate evidence revealed that TCM plus chemotherapy has obvious advantages over chemotherapy alone in terms of tumor responses, QOL, peripheral blood lymphocyte levels, and fewer AEs in the treatment of GC. The potential important targets and core genes were displayed. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021252500.Copyright © 2022 Ren, Yu, Qian, Ye, Zhu, Yu, Sun and Zhang.

Ren, Y., et al. (2023). "Should acupuncture become a complementary therapy in the treatment of uterine fibroid: a systematic review and meta-analysis of randomized controlled trials." Frontiers in Medicine 10: 1268220.
	Background: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age. The most effective treatment is myomectomy, but there is no long-term or low-invasive treatment option exists. Acupuncture can be used to treat UFs in a variety of ways. However, there is no meta-analytic synthesis including valid data that explored the efficacy of acupuncture for UFs.; Objective: To assess the efficacy and safety of acupuncture for treating UFs.; Methods: The PRISMA 2020 checklist was used. We identified and extracted the trials through may 2023 from six databases. The quality of the trials was assessed using the risk of bias (2.0). Meta-analysis was performed using RevMan 5.4 software, and it was synthesized using the random-effects model if the included studies were in high heterogeneity. Subgroup and sensitivity analysis were used if necessary.; Results: A total of 1,035 trials were identified, of which 11 were included in the review and meta-analysis. In terms of acupuncture scheme design and fibroid-related symptoms, the trials are highly heterogeneous. All 11 trials have reported acupuncture types, with traditional acupuncture and electroacupuncture being the more representative subgroups. A qualitative review of existing evidence shows that acupuncture has no serious adverse reaction on UFs. Meta-analysis shows that acupuncture can effectively reduce the volume of UFs (MD - 3.89, 95% CI - 5.23 to - 2.56, P < 0.00001) or uterine volume (MD - 16.22, 95% CI - 19.89 To - 12.55, p < 0.00001), reduce the score of fibroid symptoms (MD - 3.03, 95% CI - 3.45 to - 2.60, p < 0.00001), improve the treatment efficiency (RR: 0.19, 95% CI: 0.13 to 0.25, p < 0.00001), and likely do not affect the estrogen level.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ren, Zhang, Wu, Yuan, Wang, Tang, Liao and Liu.)

Renaud Elizabeth, J., et al. (2019). "Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee systematic review." Journal of pediatric surgery 54(3): 369-377.
	Background: The treatment of ovarian masses in pediatric patients should balance appropriate surgical management with the preservation of future reproductive capability. Preoperative estimation of malignant potential is essential to planning an optimal surgical strategy.; Methods: The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee drafted three consensus-based questions regarding the evaluation and treatment of ovarian masses in pediatric patients. A search of PubMed, the Cochrane Library, and Web of Science was performed and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify articles for review.; Results: Preoperative tumor markers, ultrasound malignancy indices, and the presence or absence of the ovarian crescent sign on imaging can help estimate malignant potential prior to surgical resection. Frozen section also plays a role in operative strategy. Surgical staging is useful for directing chemotherapy and for prognostication. Both unilateral oophorectomy and cystectomy have been used successfully for germ cell and borderline ovarian tumors, although cystectomy may be associated with higher rates of local recurrence.; Conclusions: Malignant potential of ovarian masses can be estimated preoperatively, and fertility-sparing techniques may be appropriate depending on the type of tumor. This review provides recommendations based on a critical evaluation of recent literature.; Type of Study: Systematic review of level 1-4 studies.; Level of Evidence: Level 1-4 (mainly 3-4). (Copyright © 2018. Published by Elsevier Inc.)

Rene, P., et al. (2022). "Pre-operative brachytherapy for cervical cancer: A systematic review." PROSPERO International prospective register of systematic reviews.
	
Research Comprehensive Support Project for, O. (2021). Patient Reported Outcomes Study Using Electronic Monitoring System for Advanced or Metastatic Solid Cancer.
	No Results Available Other: e-PRO monitoring Overall Survival (OS)|HRQoL EORTC Quality of Life of Cancer Patients (QLQ-C30) global health status score|HRQoL EORTC Quality of Life of Cancer Patients (QLQ-C30) domain score|HRQoL EQ-5D-5L index score|Quality-adjusted life year (QALY) score|At-home mortality rate|Time from last completion of drug therapy to death|Number of unscheduled hospital visits during drug therapy|Relative Dose Intensity (RDI)|Total number of drug regiments|Incremental Cost-Effectiveness Ratio (ICER)|Communication between patients and healthcare providers (EORTC QLQ-COMU26 score) All Not Applicable 500 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment PRO-MOTE March 31, 2027

Reszegi, K. (2022). "Verbal cognition and hormone replacement during menopause: A meta-analysis." Dissertation Abstracts International: Section B: The Sciences and Engineering 83(3-B): No-Specified.
	Background: A highly varied cognitive complaints and neuropsychological changes accompanying the menopausal transition have been documented in the literature to date. Past studies suggest that verbal memory and fluency, are especially sensitive to changes in estrogen levels. Animal research has demonstrated the neuroprotective effects of estrogen in vivo and additionally, some recent clinical trials have shown significant benefits of estrogen therapy, especially when administered during the onset and first year of menopause. However, it remains unclear if hormone replacement therapy (HRT) and other treatments, such as soy isoflavones (SIF) and selective estrogen receptor modulators (SERMs), that show estrogen-like effects, provide clinically meaningful benefits in verbal cognition for generally healthy women. Method: In this meta-analysis eight databases were searched for articles that examined the neuropsychological functioning of menopausal women receiving HRT, SIF and/or SERMs. Some of the inclusion criteria were the use of a randomized controlled design and standardized neuropsychological testing. Exclusion criteria included significant medical or neurologic comorbidities or use of medications that may influence cognition. Results: 35 articles met the inclusion criteria (Total Sample n = 8652) and provided effect size data for 6 domains, immediate verbal memory, delayed verbal memory, verbal memory recognition, confrontation naming, semantic and phonemic verbal fluency, none of which reached statistical significance. Secondary analyses revealed that treatment type was associated with differential effects among domains with SIF showing a small but statistically significant positive effect on delayed verbal memory. However, it is warranted to interpret these results with caution as the sample sizes associated with them are relatively small. Conclusions: Results suggest that generally healthy menopausal women are not likely to experience clinically significant benefits in verbal cognition as a result of using HRT, SIF or SERMs and, as such, providers may choose not to use these treatments when seeking to address common cognitive complaints associated with the menopausal transition. Future directions in research on this topic may show differential results for cognitive domains, less commonly reported in subjective memory complaints associated with aging, such as attention and working memory. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Reuter, S., et al. (2022). "The impact of Enhanced Recovery after Surgery (ERAS) pathways with regard to perioperative outcome in patients with ovarian cancer." Archives of Gynecology and Obstetrics 306(1): 199-207.
	Purpose: Major surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured "Enhanced Recovery after Surgery (ERAS)" program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer.; Methods: 134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital.; Results: Preoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p < 0.001), indicating a higher surgical risk in the ERAS group. Total number of postoperative complications (ERAS: 29.8% vs. pre-ERAS: 52.8%, p = 0.011), and length of hospital stay (ERAS: 11 (6-23) vs pre-ERAS: 13 (6-50) days; p < 0.001) differed significantly. A lower fraction of patients of the ERAS group (87.2%) needed postoperative admission to the ICU compared to the pre-ERAS group (97.7%), p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group.; Conclusion: The implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated. (© 2021. The Author(s).)

Revazova, Z. V., et al. (2021). "Current trends in the pharmacotherapy of uterine myoma, associated with heavy menstrual bleeding and anemia: A literature review." Obstetrics, Gynecology and Reproduction 15(1): 80-92.
	Aim: to summarize up-to-date world data on current opportunities of drug therapy in treatment of symptomatic myoma accompanied with heavy menstrual bleeding and anemia. Materials and Methods. A search of publications was carried out in the main international databases published in Russian and English: PubMed/MEDLINE, The Cochrane Library, Embase, and eLibrary. The analysis included studies published over the last 10 years examining the clinical efficacy and safety of various groups of pharmacological agents used for treatment of uterine myoma combined with heavy menstrual bleeding in women of reproductive age. Results. Currently, treatment of uterine fibroids consists of the three major approaches: surgical, minimally invasive organ-preserving methods, and pharmacotherapy. Until now, surgical intervention remains the main method of treatment, unfortunately being often performed in a foem of hysterectomy. However, today it is important to apply a personalized approach to the management of a female patient with symptomatic uterine myoma, taking into account her wish to preserve reproductive function. Advances in drug therapy greatly contributed to optimizing management of such patients. Conclusion. Treatment of symptomatic uterine fibroids globally tends to lowering the number of radical interventions, as well as develop and improve new therapeutic approaches for. Currently, pharmacotherapy of leiomyoma can substantially improve the quality of patients' life, lower number of radical surgical interventions, optimize surgical treatment, and even fully negate, in some cases, a need for surgery.Copyright © 2021 Eco-Vector LLC. All rights reserved.

Reynolds-Wright, J. J., et al. (2021). "UTAH: using Telemedicine to improve early medical Abortion at Home: a protocol for a randomised controlled trial comparing face-to-face with telephone consultations for women seeking early medical abortion." BMJ Open 11(6): e046628.
	Introduction Early medical abortion (EMA) is a two‐stage process of terminating pregnancy using oral mifepristone (a progesterone‐receptor antagonist) followed usually 1‐2 days later by sublingual, vaginal or buccal misoprostol (a prostaglandin analogue). There are no published randomised controlled trials (RCTs) on the use of telemedicine for EMA. Our proposed research will determine if telephone consultations for EMA (the most common method of abortion in the UK) is non‐inferior to standard face‐to‐face consultations with regard to the efficacy of EMA. Methods and analysis This study will be conducted as an RCT. The recruitment target is 1222 participants. The primary outcome is success of EMA (complete abortion rate). This will be determined based on a negative low‐sensitivity urine pregnancy test result (2 weeks after misoprostol use) and absence of surgical intervention or diagnosis of ongoing pregnancy (within 6 weeks of misoprostol). Secondary outcomes include total time spent at a clinic appointment to receive EMA, self‐reported preparedness for EMA, level of satisfaction with consultation and effective contraception uptake compared with when women attend for a face‐to‐face consultation. The main analysis will be a modified intention‐to‐treat analysis. This will include all randomised women (with a viable pregnancy) using EMA and follow‐up for the main outcome. The study initiated on 13 January 2020 and is anticipated to finish in late 2021. Ethics and dissemination Ethical approval was given by the South East Scotland NHS Research Ethics Committee, reference: 19/SS/0111. Results will be published in peer‐reviewed journals, presented at clinical and academic meetings, and shared with participants via the clinic website. Trial registration number NCT04139382.

Reynolds-Wright John, J., et al. (2022). "Pain management for medical abortion before 14 weeks' gestation." The Cochrane Database of Systematic Reviews 5: CD013525.
	Background: Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of mifepristone and misoprostol. Medical abortion is known to be a painful process, but the optimal method of pain management is unclear. We sought to identify and compare pain management regimens for medical abortion before 14 weeks' gestation. OBJECTIVES: Primary objective To determine if there is evidence of superiority of any particular pain relief regimen in the management of combination medical abortion (mifepristone + misoprostol) under 14 weeks' gestation (i.e. up to 13 + 6 weeks or 97 days). Secondary objectives To compare the rate of gastrointestinal side effects resulting from different methods of analgesia To compare the rate of complete abortion resulting from different methods of analgesia during medical abortion To determine if the induction-to-abortion interval is associated with different methods of analgesia To determine if any method of analgesia is associated with unscheduled contact with the care provider in relation to pain.; Search Methods: On 21 August 2019 we searched CENTRAL, MEDLINE, Embase, CINAHL, LILACs, PsycINFO, the World Health Organization International Clinical Trials Registry and ClinicalTrials.gov together with reference checking and handsearching of conference abstracts of relevant learned societies and professional organisations to identify further studies.; Selection Criteria: We included randomised controlled trials (RCTs) and observational studies (non-randomised studies of interventions (NRSIs)) of any pain relief intervention (pharmacological and non-pharmacological) for mifepristone-misoprostol combination medical abortion of pregnancies less than 14 weeks' gestation.; Data Collection and Analysis: Two review authors (JRW and MA) independently assessed all identified papers for inclusion and risks of bias, resolving any discrepancies through discussion with a third and fourth author as required (CM and SC). Two review authors independently conducted data extraction, including calculations of pain relief scores, and checked for accuracy. We assessed the certainty of the evidence using the GRADE approach.; Main Results: We included four RCTs and one NRSI. Due to the heterogeneity of study designs, interventions and outcome reporting, we were unable to perform meta-analysis for any of the primary or secondary outcomes in this review. Only one study found evidence of an effect between interventions on pain score: a prophylactic dose of ibuprofen 1600 mg likely reduces the pain score when compared to a dose of paracetamol 2000 mg (mean difference (MD) 2.26 out of 10 lower, 95% confidence interval (CI) 3.00 to 1.52 lower; 1 RCT 108 women; moderate-certainty evidence). There may be little to no difference in pain score when comparing pregabalin 300 mg with placebo (MD 0.5 out of 10 lower, 95% CI 1.41 lower to 0.41 higher; 1 RCT, 107 women; low-certainty evidence). There may be little to no difference in pain score when comparing ibuprofen 800 mg with placebo (MD 1.4 out of 10 lower, 95% CI 3.33 lower to 0.53 higher; 1 RCT, 61 women; low-certainty evidence). Ambulation or non-ambulation during medical abortion treatment may have little to no effect on pain score, but the evidence is very uncertain (MD 0.1 out of 5 higher, 95% CI 0.26 lower to 0.46 higher; 1 NRSI, 130 women; very low-certainty evidence). There may be little to no difference in pain score when comparing therapeutic versus prophylactic administration of ibuprofen 800 mg (MD 0.2 out of 10 higher, 95% CI 0.41 lower to 0.81 higher; 1 RCT, 228 women; low-certainty evidence). Other outcomes of interest were reported inconsistently across studies. Where these outcomes were reported, there was no evidence of difference in incidence of gastrointestinal side effects, complete abortion rate, interval between misoprostol administration to pregnancy expulsion, unscheduled contact with a care provider, patient satisfaction with analgesia regi en nor patient satisfaction with abortion experience overall. However, the certainty of evidence was very low to low.; Authors' Conclusions: The findings of this review provide some support for the use of ibuprofen as a single dose given with misoprostol prophylactically, or in response to pain as needed. The optimal dosing of ibuprofen is unclear, but a single dose of ibuprofen 1600 mg was shown to be effective, and it was less certain whether 800 mg was effective. Paracetamol 2000 mg does not improve pain scores as much as ibuprofen 1600 mg, however its use does not appear to cause greater frequency of side effects or reduce the success of the abortion. A single dose of pregabalin 300 mg does not affect pain scores during medical abortion, but like paracetamol, does not appear to cause harm. Ambulation or non-ambulation during the medical abortion procedure does not appear to affect pain scores, outcomes, or duration of treatment and so women can be advised to mobilise or not, as they wish. The majority of outcomes in this review had low- to very low-certainty evidence, primarily due to small sample sizes and two studies at high risk of bias. High-quality, large-scale RCT research is needed for pain management during medical abortion at gestations less than 14 weeks. Consistent recording of pain with a validated measure would be of value to the field going forward. (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Reza, C., et al. (2023). "Acute kidney injury after gynaecological surgery - a systematic review and meta-analysis." Danish Medical Journal 70(6): A11220733.
	INTRODUCTION. Acute kidney injury (AKI) is an abruptly occurring loss of renal function, which includes both kidney injury and kidney impairment. It is associated with mortality and morbidity due to the increased risk of developing chronic kidney disease. The aim of this systematic review and meta-analysis was to determine the incidence of post-operative AKI in gynaecological patients without pre-existing kidney injury. METHODS. Systematic searches were made for studies examining the association between AKI and gynaecological surgery published between 2004 and March 2021. The primary outcome was to compare two subgroups of studies; a screening group where AKI was diagnosed by systematic clinical screening and a non-screening group where AKI was diagnosed randomly. RESULTS. Among the 1,410 records screened, 23 studies met the inclusion criteria, reporting AKI in 224,713 patients. The pooled incidence for post-operative AKI after gynaecological surgery in the screening subgroup was 7% (95% confidence interval (CI): 0.04-0.12). The overall pooled result for post-operative AKI after gynaecological surgery in the non-screening subgroup was 0% (95% CI: 0.00-0.01). CONCLUSION. We found a 7% overall risk of post-operative AKI after gynaecological surgery. We found a higher incidence of AKI in the studies screening for kidney injury, illustrating that the condition is underdiagnosed when not screened for. An important risk exists of healthy women developing severe renal damage as AKI is a common post-operative complication with a potentially severe outcome that may be prevented in early diagnosis.Copyright © 2023, Almindelige Danske Laegeforening. All rights reserved.

Reza, M., et al. (2023). "Efficacy and safety of Ginger in the pain of Primary Dysmenorrhea: a systematic review and meta-analysis."
	
Rheu, K. M., et al. (2022). "Effect of Fermented Sarco Oyster (Crassostrea gigas) Extract on Muscle Strength Enhancement in Postmenopausal Females: a Randomized, Double-Blind, Placebo-Controlled Trial." International Journal of Environmental Research and Public Health 19(24).
	A randomized controlled trial (RCT) was conducted to evaluate the effect of fermented sarco oysters (FSO) on muscle strength in postmenopausal females with low muscle mass. Fifty‐two female participants were randomly divided into the experiment group (EG) or control group (CG). For 12 weeks, the EG was subjected to 1000 mg of FSO extract daily while the CG consumed the placebo extract. The muscle extension and flexion at an angular velocity of 60°/s and with respect to grip strength, body composition, and muscle growth‐related blood factors were measured at the baseline and after the trial. The difference in the quadriceps muscle extension at an angular velocity of 60°/s, grip strength on both the left and right side, and insulin‐like growth factor‐1(IGF‐1) between groups were significantly higher in the EG compared with the CG. However, no differences were found in body composition, blood pyruvate, lactate, or high‐sensitivity C‐reactive protein (hsCRP) concentration between the two groups. In conclusion, FSO supplements may improve muscle strength in postmenopausal females with relatively reduced muscle strength without a change in muscle mass.

Rhiannon, S., et al. (2022). "Omega 3 fatty acids for the treatment of dysmenorrhea: Systematic Literature Review."
	
Riancho-Zarrabeitia, L., et al. (2019). "Corticosteroid treatment in recurrent pregnancy losses: Systematic literature review." Progresos de Obstetricia y Ginecologia 62(4): 394-409.
	Background: Management of recurrent pregnancy losses is controversial due to the scarcity of literature available. Our aim is to perform a systematic review of the literature about the use of corticoids as therapy for recurrent pregnancy losses. Material(s) and Method(s): Systematic literature review including 76 papers classified in three groups: idiopathic recurrent pregnancy losses, antiphospholipid syndrome related recurrent pregnancy losses, and patients with failure of in vitro fertilisation. Result(s): Literature review shows heterogeneous results regarding the effect of corticosteroids in pregnancy outcome. They have been proved to be beneficial in idiopathic recurrent pregnancy losses and possibly in antiphospholipid syndrome related recurrent pregnancy losses. Results are controversial in women undergoing in vitro fertilisation, and conclusive metaanalysis are lacking. Regarding safety, corticosteroids have been shown to be non teratogenic. Long term high dose treatment is associated with maternal and fetal morbitidies, particularly intrauterine growth restriction, preeclampsia, gestational diabetes, gestational hypertension, premature rupture of membranes and premature birth. However, low dose corticosteroids during short periods of time have not been associated with maternal or fetal complications. Conclusion(s): The literature review supports the use of low dose corticosteroids during the first weeks of pregnancy in patients with idiopathic recurrent pregnancy losses, and possibly in antiphospholipid syndrome related recurrent pregnancy losses. Their efficacy in patients undergoing in vitro fertilisation is controversial.Copyright © 2019, Sociedad Espanola de Ginecologia y Obstetricia. All rights reserved.

Ribas-Maynou, J., et al. (2022). "Advanced Sperm Selection Strategies as a Treatment for Infertile Couples: A Systematic Review." International Journal of Molecular Sciences 23(22).
	Assisted reproductive technology (ART) is an essential tool to overcome infertility, and is a worldwide disease that affects millions of couples at reproductive age. Sperm selection is a crucial step in ART treatment, as it ensures the use of the highest quality sperm for fertilization, thus increasing the chances of a positive outcome. In recent years, advanced sperm selection strategies for ART have been developed with the aim of mimicking the physiological sperm selection that occurs in the female genital tract. This systematic review sought to evaluate whether advanced sperm selection techniques could improve ART outcomes and sperm quality/functionality parameters compared to traditional sperm selection methods (swim-up or density gradients) in infertile couples. According to preferred reporting items for systematic reviews and meta-analyses (PRISMA guidelines), the inclusion and exclusion criteria were defined in a PICOS (population, intervention, comparator, outcome, study) table. A systematic search of the available literature published in MEDLINE-PubMed until December 2021 was subsequently conducted. Although 4237 articles were recorded after an initial search, only 47 studies were finally included. Most reports (30/47; 63.8%) revealed an improvement in ART outcomes after conducting advanced vs. traditional sperm selection methods. Among those that also assessed sperm quality/functionality parameters (12/47), there was a consensus (10/12; 83.3%) about the beneficial effect of advanced sperm selection methods on these variables. In conclusion, the application of advanced sperm selection methods improves ART outcomes. In spite of this, as no differences in the reproductive efficiency between advanced methods has been reported, none can be pointed out as a gold standard to be conducted routinely. Further research addressing whether the efficiency of each method relies on the etiology of infertility is warranted.

Ribeiro Daniel, V., et al. (2020). "The impact of the HPV vaccine on the world: initial outcomes and challenges." DST j. bras. doenças sex. transm 32: 1-7.
	Introduction: Human papillomavirus (HPV) infection can be considered an epidemic in the world and in Brazil. This infection accounts for virtually all cases of cervical cancer, most malignant anal, vaginal and oropharyngeal tumors, and a large number of cases of cancer of the penis and vulva. The most effective way to prevent this infection is through vaccination. Several countries, including Brazil, have already introduced this vaccine into the public vaccination programs and are observing the real-life results of decreasing HPV-associated diseases. Objective: To evaluate the effectiveness of HPV vaccination in preventing virus-induced diseases in countries that have adopted it for a longer time, in a different scenario from clinical studies. Methods: This is a bibliographic review study in journal databases PubMed, LILACS, SciELO and Scopus, with publications dated from 2000 to 2019. The research was restricted to articles in English and Portuguese and studies conducted in humans. Ten studies that were considered relevant were selected. Furthermore, additional articles found by free search were selected. After this phase, the chosen publications were obtained in full for reassessment of their methodology and results. Results: The HPV vaccine demonstrated its effectiveness in reducing the incidence of HPV infection and/or anogenital warts and/or precancerous lesions in the seven countries analyzed by the study: Australia, Brazil, Denmark, United States of America, New Zealand, Czech Republic and Sweden. The impact was bigger in countries that introduced it earlier, such as Australia, where the vaccine virtually eliminated the incidence of genital warts in women aged under 21 years. Although Brazil implemented the vaccine a few years ago, a preliminary study was conducted in Campos dos Goytacazes, RJ, where the vaccine was implemented in 2010, showing a 55% reduction in the incidence of genital warts for women aged under 21 years old, between 2007 and 2012. Conclusion: The HPV vaccine is highly effective in protecting against HPV infection and disease in the countries where it has been implemented, with better results than those seen in clinical trials

Ribeiro, L., et al. (2022). "Therapeutic exercise versus other modalities for prevention and treatment of low back, pelvic girdle, and lumbopelvic pain during pregnancy: A review protocol." PloS One 17(9): e0274471.
	Background: The female body changes during pregnancy to create a favorable environment for fetal development which may result in musculoskeletal disorder and painful symptoms in the lumbopelvic region.; Objective: To analyze the evidence of therapeutic exercise versus other modalities to prevent and treat LBP, LGP, and LPP during pregnancy.; Methods: Full text randomized controlled trials (RCT) evaluating interventions to prevent or treat LBP, PGP, and LPP during pregnancy (any gestational age) that comparing therapeutic exercises with usual care or other modalities to reduce the incidence or severity of LBP or PGP or both during pregnancy will be included. 5 electronic databases will be searched to identify studies. Assess risk of bias in each study using the Cochrane Handbook for Systematic Reviews of Interventions and quality of overall body of evidence for all primary outcomes will be assessed for all comparisons using the approach outlined in GRADE Handbook.; Competing Interests: The authors have declared that no competing interests exist.

Riccardo, G., et al. (2021). "Cannabinoids for Chronic Primary Pain treatment: a systematic review and a meta-analysis."
	
Richards Cory, T., et al. (2021). "HIIT'ing or MISS'ing the Optimal Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of High- Versus Moderate-Intensity Exercise Prescription." Frontiers in Physiology 12: 715881.
	Introduction: Polycystic Ovary syndrome (PCOS) is a metabolic disorder associated with increased cardiovascular disease risk. Exercise is an effective treatment strategy to manage symptoms and reduce long-term health risk. High-intensity interval training (HIIT) has been suggested as a more efficient exercise mode in PCOS; however, it is not clear whether HIIT is superior to moderate intensity steady state exercise (MISS). Methods: We synthesized available data through a systematic review and meta-analysis to compare the effectiveness of isolated HIIT and MISS exercise interventions. Our primary outcome measures were cardiorespiratory fitness and insulin resistance, measured using V ˙ O 2max and HOMA-IR respectively. Results: A total of 16 studies were included. Moderate-quality evidence from 16 studies identified significant improvements in V ˙ O 2max following MISS (Δ = 1.081 ml/kg/min, p < 0.001, n = 194), but not HIIT (Δ = 0.641 ml/kg/min, p = 0.128, n = 28). Neither HIIT nor MISS improved HOMA-IR [(Δ = -0.257, p = 0.374, n = 60) and (Δ = -0.341, p = 0.078, n = 159), respectively]. Discussion: A significant improvement in V ˙ O 2max was evident following MISS, but not HIIT exercise in women with PCOS. This contrasts with previous literature in healthy and clinical cohorts that report superior benefits of HIIT. Therefore, based on available moderate-quality evidence, HIIT exercise does not provide superior outcomes in V ˙ O 2max compared with MISS, although larger high-quality interventions are needed to fully address this. Additional dietary/pharmacological interventions may be required in conjunction with exercise to improve insulin sensitivity.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Richards, Meah, James, Rees and Lord.)

Richardson, A. and K. Jayaprakasan (2021). "The Use of Androgen Priming in Women with Reduced Ovarian Reserve Undergoing Assisted Reproductive Technology." Seminars in Reproductive Medicine 39(5-6): 207-219.
	Androgen priming with either dehydroepiandrosterone (DHEA) or testosterone has been suggested as an adjunct to improve in vitro fertilization (IVF) outcomes in women with diminished ovarian reserve (DOR). Numerous studies have investigated the effects of both DHEA and testosterone on IVF outcome. The results were inconsistent, and the quality of most studies is substandard. Meta-analyses have consistently reported that DHEA does appear to significantly improve IVF outcome in women with predicted or proven poor ovarian response (POR), but these have included some normal responders and/or nonrandomized studies. Our meta-analyses including randomized controlled trials (RCTs) incorporating only women with DOR or POR suggest that DHEA confers no benefit. While meta-analyses of RCTs on the use of testosterone in women with DOR or POR showed an improved IVF outcome, most studies included are of low quality with high risk of bias. When analysis of data from studies of only low-risk bias was performed, such a benefit with testosterone was not observed. Although recruitment may well be a challenge, a large, well-designed RCT is, however, still warranted to investigate whether or not androgen priming with either DHEA or testosterone should be recommended as an adjuvant treatment for women with DOR or POR undergoing IVF.Copyright © 2021. Thieme. All rights reserved.

Ridout, A. E., et al. (2023). "Longitudinal change in cervical length following vaginal or abdominal cervical cerclage: a randomized comparison." American Journal of Obstetrics & Gynecology MFM 5(7): 100987.
	BACKGROUND: Cervical cerclage has been shown to reduce the risk of recurrent spontaneous preterm birth in a high‐risk patient population; however, the mechanism is not well understood. Transabdominal cerclage is superior to low and high vaginal cerclage in reducing early spontaneous preterm birth and fetal loss in women with previous failed vaginal cerclage. Cervical length measurements are commonly used to monitor high‐risk women and may explain the mechanism of success. OBJECTIVE: This study aimed to evaluate the rate of change in longitudinal cervical length after randomized placement of low transvaginal, high transvaginal, or transabdominal cerclage in women with a previous failed vaginal cerclage. STUDY DESIGN: This was a planned analysis of longitudinal transvaginal ultrasound cervical length measurements from patients enrolled in the Vaginal Randomised Intervention of Cerclage trial, a randomized controlled trial comparing transabdominal cerclage or high transvaginal cerclage with low transvaginal cerclage. Cervical length measurements at specific gestational ages were compared over time and between groups, using generalized estimating equations fitted using the maximum‐likelihood random‐effects estimator. In addition, cervical length measurements were compared in women with transabdominal cerclage placed before and during pregnancy. The diagnostic accuracy of cervical length as a predictor of spontaneous preterm birth at <32 weeks of gestation was explored. RESULTS: This study included 78 women who underwent longitudinal cervical length assessment (70% of the analyzed cohort) with a history of failed cerclage, of whom 25 (32%) were randomized to low transvaginal cerclage, 26 (33%) to high transvaginal cerclage, and 27 (35%) to transabdominal cerclage. Abdominal cerclage was superior to low (P=.008) and high (P=.001) vaginal cerclage at maintaining cervical length over the surveillance period (14 to 26 weeks of gestation) (+0.08 mm/week, 95% confidence interval, ‐0.40 to 0.22; P=.580). On average, the cervical length was 1.8 mm longer by the end of the 12‐week surveillance period in women with transabdominal cerclage (+1.8 mm; 95% confidence interval, ‐7.89 to 4.30; P=.564). High vaginal cerclage was no better than low cervical cerclage in the prevention of cervical shortening; the cervix shortened by 13.2 mm over 12 weeks in those with low vaginal cerclage (95% confidence interval, ‐21.7 to ‐4.7; P=.002) and by 20 mm over 12 weeks in those with high vaginal cerclage (95% confidence interval, ‐33.1 to ‐7.4; P=.002). Preconception transabdominal cerclage resulted in a longer cervix than those performed during pregnancy; this difference was significant after 22 weeks of gestation (48.5 mm vs 39.6 mm; P=.039). Overall, cervical length was an excellent predictor of spontaneous preterm birth at <32 weeks of gestation (receiver operating characteristic curve, 0.92; 95% confidence interval, 0.82‐1.00). CONCLUSION: In women with a previous failed cervical cerclage, in the next pregnancy, the cervical length in women treated with vaginal cerclage funneled and shortened over time, whereas there was preservation of cervical length in women who receive transabdominal cerclage. Cervical length remained longer in transabdominal procedures performed before pregnancy than in transabdominal procedures performed during pregnancy. Overall, cervical length was an excellent predictor of spontaneous preterm birth in our cohort. Our findings may explain the mechanism of benefit for transabdominal cerclage, with its high placement better maintaining the structural integrity of the cervix at the level of the internal os.

Rigos, I., et al. (2021). "The addition of endometrial injury to freeze-all strategy in women with repeated implantation failures." Journal of Clinical Medicine 10(10): 2162.
	(1) Background: Recurrent implantation failure (RIF) after IVF remains a challenging topic for fertility specialists and a frustrating reality for patients with infertility. Various approaches have been investigated and applied towards the improvement of clinical outcomes. Through a nonrandomized clinical trial, we evaluated the effect of the combination of hysteroscopic endometrial injury and the freeze-all technique on pregnancy parameters in a cohort of RIF patients; (2) Methods: The study group comprised of 30 patients with RIF that underwent a hysteroscopic endometrial injury prior to a frozen embryo transfer cycle; another 30 patients with RIF, comprising the control group, underwent a standard frozen cycle with no adjuvant treatment before. Live birth comprised the primary outcome. Logistic and Poisson regression analyses were implemented to reveal potential independent predictors for all outcomes. (3) Results: Live birth rates were similar between groups (8/30 vs. 3/30, p = 0.0876). Biochemical and clinical pregnancy and miscarriages were also independent of the procedure (p = 0.7812, p = 0.3436 and p = 0.1213, respectively). The only confounding factor that contributed to biochemical pregnancy was the number of retrieved oocytes (0.1618 +/- 0.0819, p = 0.0481); (4) Conclusion(s): The addition of endometrial injury to the freeze-all strategy in infertile women with RIF does not significantly improve pregnancy rates, including live birth. A properly conducted RCT with adequate sample size could give a robust answer.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Rikhraj, K., et al. (2020). "The Impact of Noncavity-Distorting Intramural Fibroids on Live Birth Rate in In Vitro Fertilization Cycles: A Systematic Review and Meta-Analysis." Journal of women's health (2002) 29(2): 210-219.
	What is the impact of noncavity-distorting intramural fibroids on live birth rates in in vitro fertilization (IVF) cycles? We searched Embase, MEDLINE, Google Scholar, Cochrane Library, and PUBMED from inception to May 2018. We included studies with women undergoing IVF treatment who had at least one noncavity-distorting intramural fibroid. The studies had to report one or more of the following outcomes: live birth rate as our primary outcome, and implantation rate, clinical pregnancy rate, or miscarriage rate as our secondary outcomes. We excluded studies where women also had submucosal fibroids or had undergone myomectomy. Two authors independently selected studies and extracted data. Methodological quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We included 15 studies with 5029 patients. Patients with noncavity-distorting intramural fibroids had 44% lower odds of live birth (estimated average odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.46-0.69) and 32% lower odds of clinical pregnancy (estimated average OR = 0.68, 95% CI = 0.56-0.83). Subgroup analysis of women with purely intramural fibroids showed significantly lower odds of live birth rates and clinic pregnancy rates. Analysis of prospective and retrospective studies shows that noncavity-distorting intramural fibroids have a significant adverse effect on live birth rates in women undergoing IVF. Further, well-designed prospective studies are needed to investigate whether removal of these fibroids improves IVF outcomes in this population.

Rimaz, S., et al. (2023). "The effect of Cornus mas fruit extract on vasomotor symptoms and sex hormones in postmenopausal women: a randomized, double-blind, clinical trial." Menopause (New York, N.Y.) 30(2): 201-207.
	Objectives: Cornus mas fruit has various antioxidants and anti-inflammatory properties, so this study aims at assessing its effect on menopausal symptoms and sex hormones in postmenopausal women.; Methods: In the current randomized, double-blind clinical trial, 84 individuals (42 per group) were participated. C mas hydroalcoholic extract was prepared, and participants received 300 mg C mas extract or placebo three times a day (900 g in total) for 8 weeks. The demographic, dietary intake, and physical activity information were gathered. Anthropometric indices were measured by standard methods. Furthermore, menopause symptoms were assessed by Greene Climacteric Scale. Also, sex hormones were measured by enzyme-linked immunosorbent assay.; Results: Based on the results, there was a significant difference in total Greene score reduction between the intervention and placebo groups (-3.19 ± 0.54, -0.76 ± 0.32, and P < 0.001). In addition, vasomotor symptoms had a remarkable decrease in the C mas extract group (P < 0.001). Also, the intervention group demonstrated a decreasing trend in the number and duration of hot flushes. Moreover, follicle-stimulating hormone remarkably decreased and estradiol increased in the intervention group (P = 0.016 and P = 0.018).; Conclusions: It has been found that the extract of C mas fruit has a favorable effect on vasomotor symptoms, sex hormones, and related complications in women experiencing menopausal symptoms.; Competing Interests: Financial disclosures/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Rimel, B. J. (2021). "A randomized, phase ii study comparing single-agent olaparib, single agent cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent or metastatic endometrial cancer." Gynecologic Oncology 162: S43‐S44.
	Objectives: The Cancer Genome Atlas and others identified genomic events suggesting that endometrial cancer (EC) should be susceptible to DNA repair inhibition. Data from pre‐clinical models suggest poly ADP‐ribose polymerase (PARP) inhibitors alone or in combination with other targeted agents may be an effective therapeutic strategy in EC. Combinations of angiogenic inhibitors and PARP inhibitors have demonstrated synergistic effects and have been well tolerated in other tumor types. This study compared two experimental arms exploring DNA repair inhibition versus cediranib alone which has previously shown promising activity in GOG 229J. Methods: A 1:1:1 randomized phase II study comparing cediranib (C) versus olaparib (O) or the combination of olaparib and cediranib (OC) for women with recurrent EC. Eligible patients had received at least 1 prior platinum containing chemotherapy but ≤2 prior lines of chemotherapy for recurrent EC. Cediranib was administered 30 mg PO daily, olaparib 300 mg PO BID and in the combination cediranib 20 mg PO daily / olaparib 300 mg PO BID. One cycle in all arms was 28 days. Primary endpoint was progression free survival (PFS) by RECIST1.1. Patients were stratified by histology (serous vs. endometrioid). Results: 120 patients were enrolled. 109 patients were treated: 34 patients C: 39 O and 36 OC. 10 patients withdrew consent prior to treatment. Median age was 66 years (range 41‐86); 47 (39.2%) serous, 62 endometrioid (51.7%) and 8 (6.7%) mixed histology. The Kaplan Meir estimated median PFS was 3.8 months for C; 2.0 months O and 5.5 months for OC. The one‐sided p value stratified log rank test comparing O vs. C was 0.935: HR 1.45 (95% CI 0.91‐2.3) and C vs. OC 0.064; HR 0.7 (95% CI: 0.43‐1.14). No new safety signals were reported. Conclusions: The combination of cediranib and olaparib demonstrated modest efficacy in patients with recurrent, metastatic or persistent EC, but was not significantly different compared to cediranib alone. The combination was safe with no unexpected toxicity. Single agent olaparib demonstrated insufficient efficacy to warrant further investigation as monotherapy in this patient population.

Ringel, N. E., et al. (2024). "Effects of Obesity on Urogynecologic Prolapse Surgery Outcomes: A Systematic Review and Meta-analysis." Obstetrics and Gynecology.
	OBJECTIVE: To systematically review the literature on outcomes of pelvic organ prolapse (POP) surgery in patients from various body mass index (BMI) categories to determine the association between obesity and surgical outcomes. DATA SOURCES: PubMed, EMBASE, and Cochrane databases were searched from inception to April 12, 2022; ClinicalTrials.gov was searched in September 2022 (PROSPERO 2022 CRD42022326255). Randomized and nonrandomized studies of urogynecologic POP surgery outcomes were accepted in which categories of BMI or obesity were compared. METHODS OF STUDY SELECTION: In total, 9,037 abstracts were screened; 759 abstracts were identified for full-text screening, and 31 articles were accepted for inclusion and data were extracted. TABULATION, INTEGRATION, AND RESULTS: Studies were extracted for participant information, intervention, comparator, and outcomes, including subjective outcomes, objective outcomes, and complications. Outcomes were compared among obesity categories (eg, BMI 30-34.9, 35-40, higher than 40), and meta-analysis was performed among different surgical approaches. Individual studies reported varying results as to whether obesity affects surgical outcomes. By meta-analysis, obesity (BMI 30 or higher) is associated with an increased odds of objective prolapse recurrence after vaginal prolapse repair (odds ratio [OR] 1.38, 95% CI, 1.14-1.67) and after prolapse repair from any surgical approach (OR 1.31, 95% CI, 1.12-1.53) and with complications such as mesh exposure after both vaginal and laparoscopic POP repair (OR 2.10, 95% CI, 1.01-4.39). CONCLUSION: Obesity is associated with increased likelihood of prolapse recurrence and mesh complications after POP repair. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022326255.

Rinku, S., et al. (2021). "Interventions for treating persistent postpartum sexual dysfunction after vaginal birth. A systematic review of randomised controlled trials: a protocol."
	
Rios-Espinosa, A., et al. (2022). "Citalopram improves vasomotor syndrome and urogenital syndrome of menopause in Mexican women: a randomized clinical trial." Archives of Gynecology and Obstetrics 306(6): 2035-2045.
	Purpose: This study aimed to determine the efficacy of non-hormonal therapy with citalopram vs fluoxetine for treating vasomotor syndrome (VMS) and urogenital syndrome of menopause (GSM) in Mexican women.; Methods: A parallel prospective randomized clinical trial was conducted in 91 postmenopausal women with a total score on the Menopause Rating Scale (MRS) ≥ 17 and with the clinical diagnosis of VSM and GSM. Patients were randomly assigned to receive citalopram (n = 49) or fluoxetine (n = 42). Follow-up was carried out at 3 and 6 months.; Results: The citalopram group experienced a significant improvement compared to the fluoxetine group in the MRS total score (p < 0.01), as well as in the psychological (p < 0.001) and somatic (p < 0.0001) domains at 3 and 6 months of follow-up. After 6 months of follow-up, the group that received citalopram decreased the relative risk (RR) to present VMS symptoms (RR = 0.30, CI 0.19-0.5, p = 0.0001), depressed mood (RR = 0.31, CI 0.15-0.6, p = 0.0002), irritability (RR = 0.40, CI 0.22-0.73, p = 0.002), anxiety (RR = 0.30, CI 0.13-0.69, p = 0.003), physical and mental exhaustion (RR = 0.35, CI 0.18-0.67, p = 0.001), sexual problems (RR = 0.18, CI 0.06-0.48, p = 0.0001), vaginal dryness (RR = 0.34, CI 0.14-0.80, p = 0.01), and urinary problems (RR = 0.36, CI 0.14-0.92, p = 0.043).; Conclusion: We conclude that citalopram tends to improve VSM and GSM symptoms in postmenopausal Mexican women. Thus, we recommend the daily use of citalopram 20 mg. However, further studies will be required to support the results of the present work. These should include a larger number of patients and a placebo group.; Clinical Trial Registration: This clinical trial was retrospectively registered by the United States National Library of Medicine in the www.; Clinicaltrials: gov database on 04/20/2022. The given test Registration Number is NCT05346445. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Riska, W. and S. a. Ashon (2021). "Cinnamon Extract Effects on Insulin Resistance, Metabolic Factors, and Menstrual Cyclicity for Women with Polycystic Ovary Syndrome: A Systematic review and Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	
Ristiani, N., et al. (2021). "The use of aromatherapy in primary dysmenorrhea." Gaceta sanitaria 35 Suppl 2: S591-S595.
	OBJECTIVE: The purpose of this review is to determine the use of aromatherapy in primary dysmenorrhea. METHOD: This is a literature review by searching article databases through Google Scholar, PubMed, ScienceDirect, Microsoft Academic, ProQuest, Semantic Scholar. The selection period for article publication is from 2015 to 2021. A total of 96 articles were obtained, and 30 articles could be entered according to the inclusion criteria. RESULTS: Thirty articles were analyzed, it is shown that aromatherapy effectively reduces the intensity of primary dysmenorrheal pain. The sample size of the 30 articles varied from 16 samples to 200 research samples, and the research design used experiments, clinical trials, and ex vivo, in vivo, and in vitro studies. CONCLUSION: Aromatherapy is an effective alternative intervention that can be used to reduce the intensity of primary dysmenorrhea pain.

Rivas, V. and G. Soto (2022). "Efficacy of therapeutic exercise in polycystic ovary syndrome. A systematic review." Clinica e Investigacion en Ginecologia y Obstetricia 49(3): 100751.
	Polycystic ovary syndrome is one of the most frequent hormonal problems in women of reproductive age, this syndrome presents many symptoms such as hormonal disorders, irregular menstrual cycles or amenorrhea, presence of masses in the ovaries, weight gain, hirsutism, acne, infertility, among other symptoms of hyperandrogenism. Physical exercise has been prescribed in these women with the aim of weight loss; however, it would be interesting to know the effects of exercise other than on weight loss. Therefore, the objective of this work is to know the effects that therapeutic exercise produces in women with this syndrome. A bibliographic search was conducted in February 2021 in the CINAHL, Medline and PubMed databases. Using the terms Medical Subject Heading (MeSH): "Exercise therapy", "Polycystic Ovary Syndrome", and "Therapeutic Exercise". Clinical trials published in the last 10 years in Spanish or English were included. After application of the exclusion criteria, 10 clinical trials resulted from the analysis. In most of the publications, aerobic exercise and progressive resistance exercise are used, verifying the effects that are achieved at the end of the treatment. An improvement in anthropometric and hormonal parameters was observed. After analysing the different results of this review, we can conclude that therapeutic exercise has a benefit in polycystic ovary syndrome, especially for hormonal levels and the menstrual cycle.Copyright © 2022 Elsevier Espana, S.L.U.

Rizzuto, I., et al. (2020). "Vascular endothelial growth factor (VEGF) inhibitors for the treatment of metastatic and recurrent cervical cancer." Cochrane Database of Systematic Reviews 2020(5): CD013605.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To evaluate the benefits and harms of anti-angiogenesis agents for the treatment of metastatic and recurrent cervical cancer.Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Rizzuto, I., et al. (2020). "Early surgical treatment versus observational management for cervical intraepithelial neoplasia 2 (CIN2)." Cochrane Database of Systematic Reviews 2020(12): CD013807.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To evaluate the efficacy and adverse events of conservative surveillance of women with proven histological CIN2 lesions.Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Rob, L., et al. (2021). "Dendritic cell vaccine (DCVAC) combined with chemotherapy (CMT) in patients with newly diagnosed epithelial ovarian carcinoma (EOC) after primary debulking surgery (PDS): biomarker exploratory analysis of a phase 2, open-label, randomized, multicenter trial." Journal of Clinical Oncology 39(15 SUPPL).
	Background: Most patients with EOC relapse despite PDS and CMT. Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to CMT stimulates antitumor immunity and improves clinical outcomes. Methods: Key eligibility criteria were FIGO stage III EOC (serous, endometrioid, or mucinous), post‐PDS with < 1 cm maximal residuum, no prior systemic therapy, and ECOG 0‐2. In part 1, patients were randomized up to 6 weeks after PDS, 1:1:1, into arm A (A; DCVAC concomitant with CMT), arm B (B; DCVAC sequential after CMT), and arm C (C; CMT). Patients were stratified by tumor residuum (0 or < 1 cm). CMT consisted of 6 cycles of carboplatin (AUC 5‐7) and paclitaxel (175 mg/m2 ). Patients in A and B received up to 10 doses of DCVAC (1×10 DCs/dose). The primary endpoint was radiologically assessed progression‐free survival (PFS). The key secondary endpoint was overall survival (OS). Results presented refer to a protocol‐defined modified intention‐to‐treat population (mITT) including patients who received ≥1 CMT dose in C or ≥1 DCVAC dose in A and B. Results: Between November 2013 and March 2016, 99 patients were randomized. At the final analysis, the mITT included 31 patients in A, 29 patients in B, and 30 patients in C. Key baseline characteristics and DCVAC exposure were comparable across treatment arms. Median PFS was 20.3 months in A, not reached in B, and 21.4 months in C, with corresponding HRs (95% CI) compared to C of 0.98 (0.48‐2.00) in A and 0.39 (0.16‐0.96) in B. The PFS benefit in B was statistically significant (p = 0.034) This was supported by a non‐significant trend in OS in A and B. Median OS was not reached in any arm at the time of median follow‐up of 66 months (34% of events). Patients with low CD8+ T‐cell counts (CD8 ) in tumor samples in A and B had significantly improved clinical outcomes compared to patients in C with CD8 : median PFS gain of 6 months (19 vs 13 months) and a more robust OS gain (median not reached vs 31 months), with minimal difference between A and B. This effect could not be attributed to statistical differences in high CD8+ T‐cell counts (CD8 ) density patients. These findings indicated the best clinical outcome in DCVAC patients with immunologically 'cold' tumors in both DCVAC arms. DCVAC showed a good safety profile with only 8 DCVAC‐related adverse events (Grade 1‐2). Conclusions: DCVAC improved PFS and OS outcomes in patients with newly diagnosed EOC, predominantly in patients with immunologically 'cold' tumors, thus representing a promising treatment option in this patient population.

Rob, L., et al. (2022). "Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial." Journal for Immunotherapy of Cancer 10(1).
	Background: Most patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2.; Methods: Patients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients' CD14 + monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1.; Results: Between November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events).; Conclusions: DCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC.; Trial Registration Number: NCT02107937, EudraCT2010-021462-30.; Competing Interests: Competing interests: LR, DC, PM, JK, LM, PB, C, PV, MP, ZN, JS, DK have nothing to declare. PK has received honoraria from SOTIO a.s. BM has received honoraria for speeches and advisory roles, and travel support from BMS and MS; and honoraria for speeches and advisory roles from MSD, Roche, Novartis, Amgen, Sanofi, Pfizer, Bayer, Eli Lilly, AstraZeneca, Astella, Servier, Janssen, Eisai, and Pierre Farbre. JF, TH, RPK, and MH are employees of SOTIO a.s. RS is an employee and minority shareholder of SOTIO a.s. JB is an employee and minority shareholder of SOTIO a.s., and holds a patient for HHP killing of tumor cells. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Roberts, L., et al. (2019). "Depression, Anxiety, and Post-traumatic Stress Disorder Following a Hypertensive Disorder of Pregnancy: A Narrative Literature Review." Frontiers in cardiovascular medicine 6: 147.
	Introduction: Pregnancy and childbirth can be a source of anxiety and worry for women. This is probably more so for women with a complicated pregnancy. Anxiety and worry may contribute to, or exacerbate, mental health disorders including depression and post-traumatic stress disorder (PTSD). Mental health is an integral part of health and well-being and poor mental health can be detrimental to the woman's welfare and her infant's behavior and cognitive development. It may be undetected, potentially leading to a burden on the woman, her family, the health system, and society. Women with complicated pregnancies, such as those with hypertensive disorders of pregnancy (HDP), may be at greater risk of poor mental health. The aim of this review was to examine whether there is an association between depression, anxiety, and PTSD in postpartum women with a history of HDP. Methods: A narrative literature review was undertaken. Using the key search terms: preeclampsia, gestational hypertension, hypertensive disorders, pregnancy complications, depression, anxiety, and post-traumatic stress disorder; electronic databases were searched to determine what is known about depression, anxiety, and PTSD after HDP. Results: In total, 17 publications were included. The relationship between HDP and depression, anxiety, and PTSD was variable between studies and inconsistent. Although some studies reported no significant association, there is a trend for increased prevalence and symptom severity of depression, anxiety, and PTSD following HDP. This trend was particularly evident following the more severe presentations of HDP. It was uncertain whether this association was due to the hypertensive disorder itself, the sequelae of the HDP, such as giving birth to a preterm baby, or it predated the pregnancy. Conclusions: Women who experience HDP may be at increased risk of developing postpartum depression, anxiety, and PTSD. Awareness of, and screening for, these mental health disorders in the postpartum period will alert clinicians to the need for additional follow-up and referral for women following HDP. More research on the benefits and risks of such an approach is needed.

Roberts, L. H., et al. (2022). "FRACTIONAL CARBON DIOXIDE VAGINAL LASER FOR THE TREATMENT OF URINARY SYMPTOMS: 12 MONTHS RESULTS." Journal of urology 207(SUPPL 5): e94.
	INTRODUCTION AND OBJECTIVE: Fractional carbon dioxide (fCO2) has been suggested to alleviate urinary symptoms such as frequency, urgency, urge urinary incontinence (UUI), and stress urinary incontinence (SUI) given its therapeutic effects on genitourinary symptoms of menopause (GSM). In a previous pilot study, we did not observe objective or subjective improvement in SUI at 6 months; however, there was a trend towards improvement for UUI. The goal of this study was to measure the effect of vaginal fCO2 laser therapy on SUI and OAB symptoms at 12 months. METHOD(S): After IRB approval, women > 18 years with urogenital symptoms were enrolled in an open-label prospective trial. A 3- month washout period was mandated for patients previously on vaginal estrogen therapy. Participants underwent 3 laser treatments, each 6 weeks apart from the previous. With baseline at time of treatment 1, cough stress test (CST) was performed at every visit while a voiding diary was completed at baseline, 6- and 12-months. Subjective data was obtained using the Incontinence-Quality of Life (I-QOL), Overactive Bladder Questionnaire short form (OABq-SF), Questionnaire for Urinary Incontinence Diagnosis (QUID), and Female Sexual Function Index (FSFI) at 6- and 12-months. ANOVA analysis with Dunnett's multiple comparison was used to compare means at each time point. RESULT(S): At time of analysis, 85 patients were enrolled. Of these, 36 patients had 12-month data and reported baseline SUI (n =25; 29%), frequency (n=28; 33%), urgency (n=29; 34%), or UUI (n=24; 28%). There was no statistically significant difference in number of SUI leaks (p=0.569) or rates of positive CST over time. Patients reported improvement on the I-QOL (mean +/- SD diff: 12.23+/-10.90, p<0.0001) and QUID SUI sub-section (mean +/- SD diff:-1.65+/-2.48, p=0.0065) at 12 months. There were no objective changes in frequency or UUI episodes, but urge intensity was significantly decreased at 12 months (mean +/- SD diff: -0.28+/-0.51, p=0.0008). This correlated with a similar improvement in the OABq- SF and QUID UUI subsection (p=0.0003 and 0.002 at 12 m, respectively). CONCLUSION(S): In this study, we have demonstrated that vaginal fCO2 laser therapy significantly reduces urge intensity and improves patient reported symptom scores up to 12 months after onset of treatment. However, objective outcomes for SUI did not improve. Vaginal fCO2 laser may be a viable treatment option for women with GSM who suffer from urinary urgency, but it does not improve SUI.

Robertson, K. and R. Wells (2023). "Black with 'Baby Blues': A Systematic Scoping Review of Programs to Address Postpartum Depression in African American Women." Maternal and Child Health Journal 27(3): 413-425.
	Objective: The literature review reports on programs and interventions that address postpartum depression (PPD) in African American women. African American women are at a higher risk of developing PPD compared to white women. The review will highlight and recommend approaches that may render positive outcomes in the future for this population.; Methods: A systematic scoping literature review was conducted using Academic Search Complete, CINAHL, APA PsycArticles, APA PsychInfo, PubMed, Social Services Abstracts, and Social Work Abstracts. Keywords used in the search included "postpartum depression," "African American," and "interventions OR programs OR therapy OR treatment." Fourteen studies were selected, analyzed, and included in the review.; Results: Group psychosocial, individual psychosocial, internet-based, and integrated care interventions were included. While many articles noted within group changes in depression symptoms, fewer studies documented between group differences. Studies that investigated subsamples of "high risk" participants or those that used "culturally tailored" approaches showed promise.; Conclusion: The literature review yielded some examples of programs/interventions that target postpartum depression in African American women; however, results were mixed. More research is needed to confirm the most effective interventions to address postpartum depression in African American women. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Robles, A., et al. (2022). "The step-up protocol increases clinical pregnancy rates compared with the step-down in patients with unexplained infertility. A randomized controlled trial." JBRA Assisted Reproduction 26(4): 599-605.
	Objective: Unexplained infertility is a relevant indication for controlled ovarian stimulation associated to intrauterine insemination. The "step-up" and "step-down" gonadotropin-based protocols were designed to reduce multiple pregnancy and ovarian hyperstimulation syndrome in polycystic ovary syndrome patients, but there is no related evidence in normoovulatory women undergoing intrauterine insemination. Our aim was to compare the efficacy and safety of both protocols with intrauterine insemination in unexplained infertility patients.; Methods: Randomized clinical trial including 145 women with unexplained infertility randomly following the step-up (n=73) or step-down (n=72) protocol. In the step-up group, patients started on day 3 of a spontaneous cycle administrating recombinant FSH 75IU sc/day, increasing it to 150IU if no response after 7 days. In the step-down, patients started administrating 150IU sc/day, constantly decreasing it to 75IU after 5 days. Recombinant hCG was administered when a follicle reached ≥18mm diameter.; Results: Clinical pregnancy rate was higher in the step-up group than in the step-down (20.5% vs . 8.3%; p =0.037). Significant differences between step-up and step-down protocols were found regarding days of rFSH administration (8.83±4.01% vs . 7.42±2.18%; p =0.001) and cancellation rate due to hyper response (8.21% vs . 25%; p =0.05). No differences were detected in miscarriage rates, multiple pregnancy rates/cycle and hyper stimulation syndrome incidence.; Conclusions: The step-up protocol is longer-lasting but more effective obtaining pregnancies than the step-down in patients with unexplained infertility undergoing intrauterine insemination. This effect could be explained by lower cancellation rates due to ovarian hyper response than the step-down protocol, with no differences in ovarian hyper stimulation syndrome incidence.

Rocconi Rodney, P., et al. (2022). "Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer." Cancer gene therapy 29(3-4): 369-382.
	Vigil® is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGFβ expression control. Part 1 is a safety assessment of Vigil (1 × 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCA wt suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCA wt patients. (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Rocconi, R. P., et al. (2021). "Maintenance vigil immunotherapy in newly diagnosed advanced ovarian cancer: efficacy assessment of homologous recombination proficient (HRP) patients in the phase IIb VITAL trial." Journal of Clinical Oncology 39(15 SUPPL).
	Background: In the VITAL (NCT02346747) trial, maintenance therapy with Vigil, an autologous tumor cell vaccine transfected with a DNA plasmid encoding GMCSF and bi‐shRNA‐furin for TGFβ expression control, following frontline platinum‐based chemotherapy led to a recurrence‐free survival (RFS) benefit in patients with advanced high‐grade ovarian cancer (HR=0.69, 90% CI 0.44‐1.07, p=0.078) and significantly in BRCA‐wt patients (HR=0.51, 90% CI 0.30‐0.88, p=0.020) ( Rocconi et al. Lancet Oncol. 2020). Here we report post‐hoc HR deficiency (HRD) subgroup analysis and identification of an additional molecular subgroup sensitive to Vigil therapy involving STRING analysis. Methods: This double‐blind, placebo‐controlled, Phase 2b study randomized 92 patients with newly diagnosed stage III/IV ovarian cancer with a complete clinical response (CR) to frontline surgery and chemotherapy. Patients received 1 x 10e7 cells/ml of Vigil or placebo intradermally once a month for up to 12 doses or disease progression. RFS was the primary endpoint assessed by blinded independent central review. HRD status was determined according to the Myriad Genetics myChoice CDx assay (HRD score < 42 for proficient). Using tumor annotated DNA polymorphism data, a protein‐protein interaction network was constructed using the STRING database. Properties of this network including topological distance and the identification of hub genes were used to predict a target molecular population sensitive to Vigil. Results: In the per‐protocol population (PP, n=91), 62 BRCA‐wt patients were tested for HRD status. Forty‐five patients were HR proficient (HRP) and 17 patients were HR deficient (HRD). No HRP patients in the Vigil group reported treatment related Grade 3 or higher adverse events. From the time of study randomization median RFS was improved with Vigil (n=25) in HRP patients compared to placebo (n=20) (Table 1). Similarly, overall survival (OS) benefit was observed in the Vigil group compared to placebo (Table 1). Improved RFS was demonstrated for a subset of patients with STRING predicted molecular profile. Conclusions: Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed clinical benefit in both BRCA‐wt and HRP molecular profile patients. Results suggest a unique molecular network that enhances sensitivity to Vigil therapy.

Rocconi, R. P., et al. (2021). "Gemogenovatucel-T (Vigil) Immunotherapy as Maintenance in Frontline Stage III/IV Ovarian Cancer (VITAL): a Randomized, Double-Blind, Placebo-Controlled, Phase 2b Trial." Obstetrical & gynecological survey 76(3): 151‐152.
	
Rocconi, R. P., et al. (2021). "Gemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer." Gynecologic Oncology 161(3): 676‐680.
	Objective: Recently, Vigil showed significant clinical benefit with improvement in relapse free (RFS) and overall survival (OS) in pre‐planned subgroup analysis in stage III/IV newly diagnosed ovarian cancer patients with BRCA wild type (BRCA‐wt) molecular profile. Here we analyze homologous recombination (HR) status of patients enrolled in the Phase 2b VITAL study and determine clinical benefit of Vigil in HR proficient (P) patients. Methods: Patients were previously enrolled in a Phase 2b, double‐blind, placebo‐controlled trial. All were in complete response with Stage III/IV high grade serious, endometroid or clear cell ovarian cancer. HR status was determined using MyChoice®CDx score (<42 = HRP) (Myriad Genetics, Inc., UT). Post‐hoc analyses were carried out using Kaplan Meier and restricted mean survival time (RMST) analysis to evaluate RFS and OS based on HR deficiency (D) status. Results: RFS was improved with Vigil (n = 25) in HRP patients compared to placebo (n = 20) (HR = 0.386; 90% CI 0.199–0.750; p = 0.007), results were verified by RMST (p = 0.017). Similarly, OS benefit was observed in Vigil group compared to placebo (HR = 0.342; 90% CI 0.141–0.832; p = 0.019). Results with OS were also verified with RMST (p = 0.008). Conclusion: Vigil exhibited clinical benefit in HRP molecular profile patients.

Rocha, A. K. L., et al. (2022). "Efficacy of bladder training in adults with overactive bladder: A systematic review protocol." MedRxiv.
	Introduction The aim of this systematic review will be to investigate and update whether bladder training can promote improvement of symptoms of overactive bladder syndrome with or without urgency urinary incontinence in adults. Methods We will perform a systematic review according to the Cochrane methodology of randomized controlled trials. An overall search strategy will be developed and adapted for each database. A bibliographic search will be conducted in eight databases - PubMed, PEDro, SciELO, LILACS, Cochrane Library, Web of Science, EMBASE, CINAHL, by manual searching. The MeSH terms will be "Bladder Training", "Bladder Drill", "Bladder Re-education", "Bladder Retraining", "Bladder Discipline", "Overactive Bladder", "Bladder, Overactive", "Overactive Urinary Bladder", "Urinary Bladder", "Overactive, Urinary Bladder", "Bladder, Urinary", "Urinary Bladder Disease", "Bladder Disease", "Bladder Detrusor Muscle" and "Detrusor Muscle, Bladder". Meta-analysis, if plausible, will be performed by the software Review Manager 5.4. Primary outcomes: symptoms of overactive bladder syndrome (urinary urgency with daytime voiding frequency, nocturia with or without urgency urinary incontinence), and cure/improvement assessed by instruments. Secondary Outcomes: quality of life, functional assessment, validated scale/questionnaire and adverse events. Quality assessment will be performed by Cochrane instrument and quality of evidence will be assessed by GRADE. Discussion This study is a review of randomized controlled studies to analyze the efficacy of bladder training in improving the symptoms of adults with overactive bladder syndrome. The study design of randomized controlled trials for a higher level of scientific evidence was chosen. The aim is to obtain results that allow further studies and evidence that this intervention generates beneficial effects in the sample studied. Trial registration Systematic review registration: PROSPERO CRD42022301522.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Rocha Mylena Naves de, C., et al. (2020). "The role played by granulocyte colony stimulating factor (G-CSF) on women submitted to in vitro fertilization associated with thin endometrium: systematic review." JBRA Assisted Reproduction 24(3): 278-282.
	Objective: To provide evidence available in the literature on the role of granulocyte colony stimulating factor (G-CSF) in women submitted to in vitro fertilization, with repeated implantation failure associated with thin endometrium.; Methods: Systematic review of the use of G-CSF, as part of assisted reproduction techniques in women with repeated embryo implantation failures associated with thin endometrium. The study was carried out in the PubMed, BIREME and Elsevier databases from 2008 to 2018, in English, Spanish and Portuguese.; Results: We included all the studies, which used intrauterine G-CSF. We found an increase in endometrial thickness in eight of the 10 studies included. Of these, the implantation rate improved significantly in two studies, but the gestation rate increased in only one. We found the highest rates of implantation (32%) and pregnancy (48%) in a non-randomized clinical trial. On the other hand, two other studies did not demonstrate an increase in endometrial thickness and in pregnancy rates in patients with thin endometrium submitted to the assisted reproduction in frozen embryo transfer cycles.; Conclusion: Studies published so far point to a positive influence on the use of G-CSF in relation to the improvement in endometrial receptivity and pregnancy rates. Therefore, there is a need for further studies to determine whether to use it, as well as the period, route of administration, dosage and duration of treatment.

Rochester University, o. and M. Health National Institute of (2023). Treatment of Post-partum Depression Using an Behavioral Intervention Called ROSE (Reach Out, Stay Strong, Essentials for Mothers of Newborns) Delivered Using an Electronic App.
	No Results Available Device: InBloom|Behavioral: ROSE proportion of participants with post-partum depression assessed using the Mini International Neuropsychiatric Interview (MINI)|mean depression severity measured using Patient Health Questionnaire (PHQ-9)|Return on Investment (ROI) Female Not Applicable 152 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment RSRB00007456|R44MH112216 July 1, 2025

Rodrigues, S., et al. (2023). "Effect of Perineal Massage and Warm Compresses Technique in Postpartum Pelvic Floor Dysfunction. A Secondary Analysis from a Randomised Controlled Trial." Reproductive Sciences.
	Pelvic floor dysfunction (PFD) is common to be associated with pregnancy and birth. To date, no research has been done to understand whether the perineal massage and warm compresses technique has an impact on pelvic floor dysfunction. To assess the impact of perineal massage and warm compresses technique during the second stage of labor in pelvic floor dysfunction at 3 and 6 months postpartum. Of the 800 women recruited to randomised controlled trial to prevent perineal trauma, 496 were included in the study, with 242 (48.8%) assigned to the Perineal Massage and Warm Compresses (PeMWaC) group and 254 (51.2%) to the control group (hands-on). Used the Pelvic Floor Distress Inventory-20 (PFDI-20). The questionnaire is divided into three subscales: Urinary (UDI), Colorectal-Anal (CRADI), and Pelvic Organ Prolapse Distress Inventory (POPDI). The PeMWaC group had a significantly higher frequency of intact perineum (p < 0.001) and low-severity vaginal tears (tears without any other degree of perineal trauma) (p = 0.031) compared to the control group, while the control group had significantly more patients who suffered high-severity vaginal/perineal trauma (second degree perineal tears) (p = 0.031) and patients without spontaneous perineal trauma or vaginal tears who underwent episiotomy (p < 0.001). In addition, at 3 months postpartum, women in the control group had a higher Urinary Distress Inventory (UDI) score and global score, compared to the PeMWaC group, and after controlling for confounding variables, the perineal massage and warm compresses technique was associated with lower UDI scores at 3 months postpartum compared to control group. At 6 months postpartum, there were no differences in the UDI or global scores, indicating general recovery from perineal trauma. In addition to reducing perineal trauma during birth, the perineal massage and warm compresses technique was associated with a lower prevalence of early PFD symptoms, mainly urinary distress, at 3 months. Trial registration http://www.ClinicalTrials.gov NCT05854888, retrospectively registered.Copyright © 2023, The Author(s), under exclusive licence to Society for Reproductive Investigation.

Rodrigues-Amorim, D., et al. (2020). "A systematic review of efficacy, safety, and tolerability of duloxetine." Frontiers in Psychiatry 11.
	Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of patients affected by major depressive disorder (MDD), generalized anxiety disorder (GAD), neuropathic pain (NP), fibromyalgia (FMS), and stress incontinence urinary (SUI). These conditions share parallel pathophysiological pathways, and duloxetine treatment might be an effective and safe alternative. Thus, a systematic review was conducted following the 2009 Preferred Reporting Items (PRISMA) recommendations and Joanna Briggs Institute Critical (JBI) Appraisals guidelines. Eighty-five studies focused on efficacy, safety, and tolerability of duloxetine were included in our systematic review. Studies were subdivided by clinical condition and evaluated individually. Thus, 32 studies of MDD, 11 studies of GAD, 19 studies of NP, 9 studies of FMS, and 14 studies of SUI demonstrated that the measured outcomes indicate the suitability of duloxetine in the treatment of these clinical conditions. This systematic review confirms that the dual mechanism of duloxetine benefits the treatment of comorbid clinical conditions, and supports the efficacy, safety, and tolerability of duloxetine in short- and long-term treatments. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Rodriguez, M. I., et al. (2021). "Medical abortion offered in pharmacy versus clinic‐based settings." Cochrane Database of Systematic Reviews(6).
	- Background Medical abortion is usually offered in a clinic or hospital, but could potentially be offered in other settings such as pharmacies. In many countries, pharmacies are a common first point of access for women seeking reproductive health information and services. Offering medical abortion through pharmacies is a potential strategy to improve access to abortion. Objectives To compare the effectiveness and safety of medical abortion offered in pharmacy settings with clinic‐based medical abortion. Search methods We searched CENTRAL, MEDLINE, Embase, four other databases, two trials registries and grey literature websites in November 2020. We also handsearched key references and contacted authors to locate unpublished studies or studies not identified in the database searches. Selection criteria We identified studies that compared women receiving the same regimen of medical abortion or post‐abortion care in either a clinic or pharmacy setting. Studies published in any language employing the following designs were included: randomized trials and non‐randomized studies including a comparative group. Data collection and analysis Two review authors independently reviewed both retrieved abstracts and full‐text publications. A third author was consulted in case of disagreement. We intended to use the Cochrane risk of bias tool, RoB 2, for randomized studies and used the ROBINS‐I tool (Risk Of Bias In Non‐randomized Studies of Interventions) to assess risk of bias in non‐randomized studies. GRADE methodology was used to assess the certainty of the evidence. The primary outcomes were completion of abortion without additional intervention, need for blood transfusion, and presence of uterine or systemic infection within 30 days of medical abortion. Main results Our search yielded 2030 records. We assessed a total of 89 full‐text articles for eligibility. One prospective cohort study met our inclusion criteria. The included study collected data on outcomes from 605 women who obtained a medical abortion in Nepal from either a clinic or pharmacy setting. Both sites of care were staffed by the same auxiliary nurse midwives. Over all domains, the risk of bias was judged to be low for our primary outcome. During the pre‐intervention period, the study’s investigators identified a priori appropriate confounders, which were clearly measured and adjusted for in the final analysis. For women who received medical abortion in a pharmacy setting, compared to a clinic setting, there may be little or no difference in complete abortion rates (adjusted risk difference (RD)) 1.5, 95% confidence interval (CI) ‐0.8 to 3.8; 1 study, 600 participants; low certainty evidence). The study reported no cases of blood transfusion, and a composite outcome, comprised mainly of infection complications, showed there may be little or no difference between settings (adjusted RD 0.8, 95% CI ‐1.0 to 2.8; 1 study, 600 participants; very low certainty evidence). The study reported no events for hospital admission for an abortion‐related event or need for surgical intervention, and there may be no difference in women reporting being highly satisfied with the facility where they were seen (38% pharmacy versus 34% clinic, P = 0.87; 1 study, 600 participants; low certainty evidence). Authors' conclusions Conclusions about the effectiveness and safety of pharmacy provision of medical abortion are limited by the lack of comparative studies. One study, judged to provide low certainty evidence, suggests that the effectiveness of medical abortion may not be different between the pharmacy and clinic settings. However, evidence for safety is insufficient to draw any conclusions, and more research on factors contributing to potential differences in quality of care is needed. It is important to note that this study included a care model where a clinician provided services in a pharmacy, not direct provision of care by pharmacists or pharmacy staff. Three ongoing studies are potentially eligible for inclusion in review updates. More re earch is eeded because pharmacy provision could expand timely access to medical abortion, especially in settings where clinic services may be more difficult to obtain. Evidence is particularly limited on the patient experience and how the care process and quality of services may differ across different types of settings. Plain language summary Medical abortion offered in pharmacy versus clinic‐based settings Why this review is important Medical abortion is offered routinely in clinics and hospitals, but could be offered in other settings such as pharmacies. In many countries, pharmacies are a first and common point of access for women seeking reproductive health information and services, including abortion. Expanding access to medical abortion through pharmacies is a potential strategy to promote safe abortion care. How did we identify and evaluate the evidence? We searched seven medical research databases for randomized controlled trials, and websites for grey literature (i.e. research produced by organizations outside of the traditional commercial and academic publishing and distribution channels). In addition, we handsearched key references and contacted authors to locate unpublished studies or studies not identified in the database searches. We identified studies that compared women receiving the same medication and dosage for medical abortion or post‐abortion care in either a clinic or pharmacy setting. We included studies published in any language, including the following designs: randomized trials and non‐randomized studies that included a comparison group. We read and evaluated all abstracts and full‐text articles, and rated our confidence in the evidence, based on factors such as study methods and sizes. What did we find? We found 2030 records. We screened the retrieved abstracts, and applied exclusion criteria. We assessed a total of 89 full‐text articles for eligibility. One prospective cohort study met our inclusion criteria. In this study, 605 women in Nepal received medical abortions from the same health care providers (auxiliary nurse midwives) in either a clinic or pharmacy‐based setting. There was no difference in complete abortion rates between the two different abortion settings. We also examined rates of blood transfusion and infection within 30 days of medical abortion. These outcomes were rare and the evidence was limited for drawing conclusions about differences by site. Additional secondary outcomes included hospital admission for an abortion‐related event, additional surgical interventions needed (besides uterine aspiration), and measures of quality of care. No hospital admissions or additional surgical procedures occurred within either group, and information about quality of care was limited. What does this mean? A single non‐randomized study provides us with low certainty that the effectiveness of medical abortion probably does not differ between the pharmacy or clinic setting when the care is provided by the same clinicians. Three ongoing studies are potentially eligible for inclusion in an update of this review. Conclusions about the effectiveness, safety and quality of care of pharmacist provision of medical abortion are limited by the lack of comparative studies. More research is needed because pharmacy provision could expand timely access to medical abortion, especially in settings where clinic services may be more difficult to obtain. How up‐to‐date is this review? The evidence in this Cochrane Review is current to November 2020.

Rodríguez-Longobardo, C., et al. (2023). "Pelvic Floor Muscle Training Interventions in Female Athletes: A Systematic Review and Meta-analysis." Sports health: 19417381231195305.
	Context: Athletes are almost 3 times more at risk of experiencing urinary incontinence (UI) than sedentary women, with prevalence rates varying from 10.9% in low-impact sports such as cycling to 80% when engaging in high-impact sports such as trampoline gymnastics. To treat UI, pelvic floor muscle (PFM) training (PFMT) is recommended as a first line of treatment.; Objective: The aim of the present study was to perform a meta-analysis of the available literature on the efficacy of PFMT interventions in young, nulliparous female athletes.; Data Sources: A literature research was conducted using PubMed, Sport Discus, and Web of Science.; Study Selection: The inclusion criteria were studies with PFMT intervention in female athletes or recreationally active women. Interventions could be carried out for treatment or prevention of pelvic floor dysfunctions.; Study Design: Systematic review with meta-analysis.; Level of Evidence: Level 5.; Data Extraction: A descriptive analysis of the articles included in the systematic review was carried out. Meta-analyses could be performed on 6 of the included articles, evaluating the maximal voluntary contraction (MVC) of the PFMs, the amount of urinary leakage (AUL), and the vaginal resting pressure (VRP). Random-effects model and standardized mean differences (SMD) ± 95% CI were reported.; Results: The meta-analysis showed that PFMT produced a significant increase in MVC (SMD, 0.60; 95% CI, 0.11 to 1.08; P = 0.02) and a significant reduction of AUL (SMD, -1.13; 95% CI, -1.84 to -0.41; P < 0.01) in female athletes. No effects were shown in VRP (SMD, -0.05; 95% CI, -1.27 to 1.17; P = 0.93).; Conclusion: PFMT is shown to be effective in increasing PFM strength and reducing urine leakage in female athletes, being a powerful tool to prevent and treat pelvic floor dysfunction in this population.

Roe, A. H., et al. (2021). "The effect of mifepristone pretreatment on bleeding and pain during medical management of early pregnancy loss." Contraception 104(4): 432-436.
	OBJECTIVES: To compare participant-reported bleeding and pain with two medication regimens for early pregnancy loss (EPL). STUDY DESIGN: We performed a secondary analysis of a randomized trial in which participants took either mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 24 hours later or misoprostol alone for medical management of EPL. Participants reported bleeding and pain (Numeric Pain Rating Scale, NPRS, 0-10) with daily paper diaries and at study visits on trial days 3, 8, and 30. We used, Fisher's exact, Pearson chi-square, Wilcoxon rank sum, and Student's t-tests to compare onset, duration, and severity of bleeding and pain symptoms between trial arms after misoprostol administration. RESULTS: Among 291 participants who submitted diary data, 143 received mifepristone pretreatment. A larger proportion of this group reported moderate or heavy bleeding on trial day 2, the day of misoprostol administration, compared with those who did not receive pretreatment (73% vs 47%, p < 0.01). Between days 4 and 8, more mifepristone-pretreatment participants reported mild or no bleeding, compared with the misoprostol-only arm (78% vs 61%, p < 0.01). Average pain score for trial days 2-4 was higher for the pretreatment group compared with the misoprostol-only group (6.9 vs 6.0, p = 0.01), and there was a trend toward shorter total duration of pain (15 vs 19 hours, p = 0.08). These differences remained after controlling for treatment success across arms. CONCLUSIONS: Mifepristone pretreatment increased the severity of pain but not bleeding and resulted in a shorter trajectory of symptoms during medical management of EPL. IMPLICATIONS: Mifepristone pretreatment decreases the duration of heavy bleeding and there was a trend toward decreased duration of pain during medical management of miscarriage, indicating that this medication improves the efficiency, in addition to the efficacy, of this treatment.

Rogers Rebecca, G., et al. (2022). "Improved body image after uterovaginal prolapse surgery with or without hysterectomy." International Urogynecology Journal 33(1): 115-122.
	Introduction and Hypothesis: The objective was to compare body image and sexual activity and function changes up to 3 years after sacrospinous ligament fixation with graft hysteropexy or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy).; Methods: This was a planned secondary analysis of a multi-center randomized trial of women undergoing prolapse repair with mesh hysteropexy versus hysterectomy. Women were masked to intervention. The modified Body Image Scale (BIS), sexual activity status, and Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) scores were reported at baseline and 1.5, 6, 12, 18, 24, and 36 months after surgery. We compared mean BIS and PISQ-IR scores, the proportion of women whose BIS scores met a distribution-based estimate of the minimally important difference (MID), and sexual activity status. Comparisons were analyzed with linear and logistic repeated measures models adjusted for site, intervention, visit, and intervention by visit interaction.; Results: Eighty-eight women underwent mesh hysteropexy; 87 underwent hysterectomy. Women were similar with regard to baseline characteristics, mean age 65.9 ± 7.3 years, and most had stage III or IV prolapse (81%). Baseline mean BIS scores were not significantly different, improved in both groups by 1.5 months, and were sustained through 36 months with no differences between groups (all p > 0.05). The estimated BIS MID was 3; and by 36 months, more women in the mesh hysteropexy group achieved the MID than in the hysterectomy group (62% vs 44%, p = 0.04). The makeup of the sexually active cohort changed throughout the study, making function comparisons difficult.; Conclusions: Body image improves following prolapse surgery whether or not hysterectomy is performed or transvaginal mesh is used at the time of repair; sexual activity status changes over time following prolapse surgery. (© 2021. The International Urogynecological Association.)

Rogers Sarah, K., et al. (2023). "Efficacy of psychological interventions for dysmenorrhea: a meta-analysis." Pain medicine (Malden, Mass.) 24(9): 1086-1099.
	Dysmenorrhea is pelvic pain associated with menstruation and is one of the most common pain conditions among reproductive-age women. It is commonly treated with medications, complementary and alternative medicine, and self-management techniques. However, there is increased focus on psychological interventions which modify thoughts, beliefs, emotions, and behavioral responses to dysmenorrhea. This review examined the efficacy of psychological interventions on dysmenorrhea pain severity and interference. We conducted a systematic search of the literature using PsycINFO, PubMed, CINHAL, and Embase. A total of 22 studies were included; 21 examined within-group improvement (ie, within-group analysis) and 14 examined between-group improvement (ie, between-group analysis). Random-effects meta-analyses were conducted on pain severity and interference, with average effect sizes calculated using Hedges's g. Within-group analyses showed decreased pain severity and interference at post-treatment (g = 0.986 and 0.949, respectively) and first follow-up (g = 1.239 and 0.842, respectively). Between-group analyses showed decreased pain severity at post-treatment (g = 0.909) and decreased pain severity and interference at first follow-up (g = 0.964 and 0.884, respectively) compared to control groups. This review supports the efficacy of psychological interventions for dysmenorrhea, but conclusions are tempered by suboptimal methodological quality of the included studies and high heterogeneity across studies. Additional, rigorous research is needed to determine the clinical utility of psychological interventions for dysmenorrhea. (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rogier-Mouzelas, F., et al. (2023). "Anatomic and functional results of ventral biological mesh rectopexy for posterior pelvic floor disorders." Journal of visceral surgery 160(3): 188-195.
	Introduction: Ventral mesh rectopexy (VMR) is the gold standard for rectal prolapse surgery, but the type of mesh reinforcement is still a matter of debate. The aim of this study was to assess the anatomic and functional results of a single center cohort of patients receiving ventral rectopexy with biological mesh compared to a reference group who had implantation of synthetic mesh. We also assessed the predictive factors for recurrence.; Patients and Methods: Seventy patients (2015-2021) were included in the biological mesh group and were compared to a reference group of 345 patients operated on with a synthetic mesh (2004-2017).; Results: In the biological mesh group, the mean age of patients was 65 years (53-72). The main disorders of the posterior pelvic floor were rectal prolapse (30 cases) or rectocele (37 cases). Two patients had solitary rectal ulcer syndrome and one had internal prolapse. VMR was performed by a laparoscopic approach with robotic assistance in 93%. After a median follow-up of 12 (4.5-23) months, the anatomic recurrence rate was 10%. The median satisfaction score assessed in a telephone interview by a semi-quantitative scale from 0 to 10 was 7. Compared to the synthetic group, neither the morbidity rate (Dindo>2) (0.6% synthetic versus 1.4% biological mesh), nor the recurrence rate (12% synthetic versus 10% biological (ns) with an average interval of 13.5 versus 14 months, respectively) were statistically significantly different.; Conclusion: VMR with biological mesh represents an alternative to synthetic mesh. Despite its resorbable nature, biological mesh does not seem to increase the risk of recurrence and offers satisfying functional results after a medium term follow-up. (Copyright © 2022. Published by Elsevier Masson SAS.)

Rogo-Gupta, L. J., et al. (2022). "Low-fat dietary pattern reduces urinary incontinence in postmenopausal women: post hoc analysis of the Women's Health Initiative Diet Modification Trial." AJOG Global Reports 2(1): 100044.
	BACKGROUND: Urinary incontinence affects >40% of women in the United States, with an annual societal cost of >$12 billion and demonstrated associations with depressive symptoms, social isolation, and loss of work productivity. Weight has been established as an exposure that increases urinary incontinence risk and certain dietary components have been associated with urinary incontinence symptoms. We hypothesized that diet plays a key role in the association between weight and urinary incontinence in US women. OBJECTIVE(S): This study aimed to examine the effect of a low-fat diet on urinary incontinence in postmenopausal women as a post hoc analysis of a randomized controlled trial of diet modification. STUDY DESIGN: This was a post hoc analysis of the Women's Health Initiative Dietary Modification randomized controlled trial of 48,835 postmenopausal women from 40 US centers assigned to a dietary intervention (20% energy from fat, 5 fruits or vegetable servings, and 6 whole grain servings daily and an intensive behavioral modification program) or to the usual diet comparison group. The outcome was urinary incontinence at 1 year. RESULT(S): Of the participants, 60% were randomized to the usual diet comparison group and 40% to the dietary modification intervention. After adjusting for weight change, women assigned to the dietary modification intervention were less likely to report urinary incontinence (odds ratio, 0.94; 95% confidence interval, 0.90-0.98; P=.003), more likely to report urinary incontinence resolution (odds ratio, 1.11; 95% confidence interval, 1.03-1.19; P=.01), and less likely to develop urinary incontinence (odds ratio, 0.92; 95% confidence interval, 0.87-0.98; P=.01) in adjusted models. CONCLUSION(S): Dietary modification may be a reasonable treatment for postmenopausal women with incontinence and also a urinary incontinence prevention strategy for continent women. Our results provide evidence to support a randomized clinical trial to determine whether a reduced fat-intake dietary modification is an effective intervention for the prevention and treatment of urinary incontinence. In addition to providing further insights into mechanisms of lower urinary tract symptoms, these findings may have a substantial impact on public health based on the evidence that diet seems to be a modifiable risk factor for urinary incontinence.Copyright © 2021 The Authors

Roland, A., et al. (2023). "Enhancing surgical performance: the role of robotic surgery in myomectomies, a systematic review and metanalysis."
	
Roland, C. B., et al. (2021). "Structured supervised exercise training or motivational counselling during pregnancy on physical activity level and health of mother and offspring: FitMum study protocol." BMJ Open 11(3): e043671.
	INTRODUCTION: A physically active lifestyle during pregnancy improves maternal and offspring health but can be difficult to follow. In Denmark, less than 40% of pregnant women meet physical activity (PA) recommendations. The FitMum study aims to explore strategies to increase PA during pregnancy among women with low PA and assess the health effects of PA. This paper presents the FitMum protocol, which evaluates the effects of structured supervised exercise training or motivational counselling supported by health technology during pregnancy on PA level and health of mother and offspring. METHODS AND ANALYSIS: A single-site three-arm randomised controlled trial that aims to recruit 220 healthy, pregnant women with gestational age (GA) no later than week 15 and whose PA level does not exceed one hour/week. Participants are randomised to one of three groups: structured supervised exercise training consisting of three weekly exercise sessions, motivational counselling supported by health technology or a control group receiving standard care. The interventions take place from randomisation until delivery. The primary outcome is min/week of moderate-to-vigorous intensity PA (MVPA) as determined by a commercial activity tracker, collected from randomisation until GA of 28 weeks and 0-6 days, and the secondary outcome is gestational weight gain (GWG). Additional outcomes are complementary measures of PA; clinical and psychological health parameters in participant, partner and offspring; analyses of blood, placenta and breastmilk samples; process evaluation of interventions; and personal understandings of PA. ETHICS AND DISSEMINATION: The study is approved by the Danish National Committee on Health Research Ethics (# H-18011067) and the Danish Data Protection Agency (# P-2019-512). Findings will be disseminated via peer-reviewed publications, at conferences, and to health professionals via science theatre performances. TRIAL REGISTRATION NUMBER: NCT03679130. PROTOCOL VERSION: This paper was written per the study protocol version 8 dated 28 August 2019.

Roman, H., et al. (2022). "Long-term Outcomes Following Surgical Management of Rectal Endometriosis: Seven-year Follow-up of Patients Enrolled in a Randomized Trial." Journal of Minimally Invasive Gynecology 29(6): 767-775.
	Study Objective: To compare functional outcomes, recurrence rate, and pregnancy likelihood in patients undergoing conservative or radical surgery for deep rectal endometriosis followed up for 7 years.; Design: Prospective study in a cohort of patients enrolled in a 2-arm randomized trial from March 2011 to August 2013.; Setting: A tertiary referral center.; Patients: Fifty-five patients with deep endometriosis infiltrating the rectum.; Interventions: Patients underwent either segmental resection or nodule excision via shaving or disk excision, depending on randomization that was performed preoperatively using sequentially numbered, opaque sealed envelopes.; Measurements and Main Results: The primary end point was the number of patients experiencing one of the following symptoms: constipation, frequent bowel movements, anal incontinence, or bladder dysfunction 24 months after surgery. The secondary end points were values of gastrointestinal and overall quality of life scores. The 7-year recurrence rates (new deep endometriosis nodules infiltrating the rectum) in the excision vs segmental resection arms were 7.4 % vs 0% (p = .24). One of the symptoms included in the definition of the primary outcomes was recorded in 55.6% vs 60.7% of patients (p = .79). However, 51.9% vs 53.6% of patients considered their bowel movements as normal (p = .99). An intention-to-treat comparison of overall quality of life scores did not find a difference between the 2 groups 7 years after surgery. At the end of the 7-year study period, 31 of 37 patients who tried to conceive were successful (83.8%), including 27 pregnancies (57.4%) resulting from natural conception and 20 pregnancies (42.6%) resulting from assisted reproductive technology procedures. The pregnancy rate was 82.4% vs 85% in the 2 arms (p = .99). A 75.7% live birth rate was recorded. At the end of the follow-up, there were 15 women with 1 child (40.5%) and 13 women with 2 children (35.1%). During the 7-year follow-up, the reoperation rates were 37% and 35.7%, respectively, in each arm (p = .84). Among the 27 reoperation procedures during the follow-up period, 11 (40.7%) were for postoperative complications, 7 (25.9%) were necessary before assisted reproductive technology management, 8 (29.6%) were for recurrent abdominal or pelvic pain, and 1 (3.7%) was for midline ventral hernia after pregnancy.; Conclusion: Our study did not reveal a considerable difference in terms of digestive functional outcomes, recurrence rate, reoperation risk, and pregnancy likelihood when conservative and radical rectal surgeries for deep endometriosis were compared 7 years after surgery. The postoperative pregnancy rate observed in our series was high. (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Roman, M., et al. (2020). "The efficiency of online cognitive-behavioral therapy for postpartum depressive symptomatology: a systematic review and meta-analysis." Women & Health 60(1): 99-112.
	International. Six studies were selected based on the following eligibility criteria: (1) papers published in English, (2) papers about PD, (3) papers that empirically investigated the effectiveness of OCBT for PD, and (4) papers comparing an experimental group with a control group. Exclusion criteria included investigations of PD for: (1) mothers diagnosed with another severe disorder and (2) mothers with deceased children and (3) women with an age below 18 years old. This meta-analytic study identified a moderate significant size-effect ( d = - 0.54, 95% CI [-0.716; -0.423]) of the OCBTs in reducing PD, and practical implications and limitations are discussed.

Romero-Franco, N., et al. (2021). "Therapeutic exercise to improve pelvic floor muscle function in a female sporting population: a systematic review and meta-analysis." Physiotherapy 113: 44-52.
	Background: Despite the high prevalence of pelvic floor dysfunction (PFD) among women who participate in sports, and the efforts made to affect these pathologies through pelvic floor muscle (PFM) training, its effects on PFM function remain unclear.; Objective: To evaluate the effects of therapeutic exercise programmes on PFM function and quality of life in female athletes and physically active women.; Data Sources: The following databases were searched: MEDLINE, SCIELO, LILACS, SPORTDiscus, SCOPUS, CINHAL, SCIELO, PEDro, ScienceDirect and COCHRANE from January 2010 to May 2020.; Study Selection: Study selection criteria included clinical trials that recruited either female athletes or physically active women, and evaluated the effects of therapeutic exercise programmes on PFM function.; Data Synthesis: Ten studies met the eligibility criteria, capturing a total of 246 participants, of which 180 were apparently healthy individuals and 66 suffered from PFD.; Results: Meta-analysis revealed significant improvements in maximal voluntary contraction of the PFMs and reduction of urine leakage after the exercise programmes, although no effects were found for vaginal resting pressure.; Limitations: Most of the studies reviewed had a small sample size and a high risk of bias.; Conclusions and Implications of Key Findings: Data suggest the benefits of therapeutic exercise on PFM function, PFD symptoms and quality of life after therapeutic exercise programmes in women who participate in sports. Incorporating therapeutic exercises designed to increase PFM function into physical activity routines could be beneficial for both healthy women and those suffering from PFD. However, due to the stated limitations, firm conclusions cannot be made. Systematic Review Registration Number PROSPERO CRD42020167243. (Copyright © 2021 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Rondanelli, M., et al. (2022). "A 60-Day Green Tea Extract Supplementation Counteracts the Dysfunction of Adipose Tissue in Overweight Post-Menopausal and Class I Obese Women." Nutrients 14(24).
	Menopause is characterized by weight gain and increased visceral fat, which acts as an endocrine organ secreting proinflammatory adipocytokines, with consequent increased risk of metabolic disorders. The aim of this double‐blind, placebo‐controlled randomized trial was to evaluate the effects of a 60‐day dietary supplementation using Camellia sinensis leaf extract on adipose tissue dysfunction in overweight or class I obese post‐menopausal, sedentary women. Primary endpoints were the respiratory quotient (RQ), the percentage of carbohydrates (%CHO), the percentage of fat oxidation (%FAT), and the resting energy expenditure (REE) measured by indirect calorimetry. Secondary endpoints included body composition, by dual x‐ray absorptiometry (DXA), glucose profile, lipid profile, inflammatory state, liver and kidney function, hormonal status regarding satiety, and status of catecholamines. Twenty‐eight women were randomized into two groups: 14 (BMI 31.1 ± 3.5) were supplemented and 14 (BMI 31.9 ± 2.2) received placebo. In regards to the between‐group differences over time (β), a statistically significant difference between the supplemented and placebo group was observed for: RQ (β = −0.04, p = 0.009), % fat oxidation (β = 11.04, p = 0.0006), insulin (β = −1.74, p = 0.009), HOMA (β = −0.31, p = 0.02), waist circumference (β = −1.07, p = 0.007), REE (β = 83.21, p = 0.009), and CRP (β = −0.14, p = 0.02). These results demonstrate that a 60‐day green tea extract supplementation counteracts the dysfunction of adipose tissue in overweight post‐menopausal and class I obese women.

Rong, A., et al. (2023). "Add-on effect of the Guizhi Fuling formula for management of reduced fertility potential in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials." Frontiers in Endocrinology 13: 995106.
	Background: Guizhi Fuling (GZFL) pill, a traditional Chinese herbal formula including Semen Persicae , Ramulus Cinnamomi , Poria , Radix Paeoniae Alba , and Cortex Moutan , has been widely applied in the management of gynecological diseases.; Objective: To evaluate the add-on effect of the GZFL formula for treating reduced fertility potential in women with polycystic ovary syndrome (PCOS) by conducting a systematic review and meta-analysis.; Methods: Two reviewers independently searched the PubMed, Embase, Cochrane Library, Wanfang, SinoMed, and CKNI databases until 09/11/2022. Eligible studies were randomized controlled trials (RCTs) of the GZFL formula plus Western medicine versus the Western medicine for treating PCOS. The primary endpoint was the ovulation, pregnancy, and miscarriage rate. The secondary endpoints included the serum follicle-stimulating hormone (FSH), total testosterone, luteinizing hormone (LH), estradiol, and homeostasis model assessment insulin resistance (HOMA-IR).; Results: There were 16 RCTs with 1,385 patients identified. The GZFL formula plus Western medicine significantly improved the ovulation rate (risk ratios [RR] 1.24; 95% confidence intervals [CI] 1.15-1.34) and pregnancy rate (RR 1.53; 95% CI 1.38 to 1.69) than the Western medicine alone. Adjuvant treatment with the GZFL formula also significantly decreased the serum FSH (mean difference [MD] -0.48 U/l; 95% CI -0.80 to -0.15), total testosterone (standard mean difference [SMD] -1.07; 95% CI -1.71 to -0.44), LH level (MD -2.19 U/l; 95% CI -3.04 to -1.34), and HOMA-IR (MD -0.47; 95% CI -0.60 to -0.34). However, there was no significant difference in the miscarriage rate (RR 0.89; 95% CI 0.36-2.20) and serum estradiol level (SMD 0.34; 95% CI -0.25 to 0.94) between two groups.; Conclusions: The GZFL formula as adjuvant therapy can improve the ovulation and pregnancy rates in women with PCOS. Its beneficial effects may correlate with reducing FSH, total testosterone, and LH and ameliorating insulin resistance. However, more well-designed RCTs with larger samples and multicenter trials are required to confirm the current findings due to uncertainty of the evidence.; Systematic Review Registration: PROSPERO identifier, CRD42022354530.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Rong, Ta, E. and Meng.)

Rong, T. and Y. Junlan (2021). "Cognitive- behavioral therapy improves quality of life in women with polycystic ovary syndrome : a meta -analysis." PROSPERO International prospective register of systematic reviews.
	
Ronsini, C., et al. (2022). "The Oncological Implication of Sentinel Lymph Node in Early Cervical Cancer: A Meta-Analysis of Oncological Outcomes and Type of Recurrences." Medicina (Kaunas, Lithuania) 58(11).
	Background and Objectives : Pelvic lymphadenectomy has been associated with radical hysterectomy for the treatment of early Cervical Cancer (ECC) since 1905. However, some complications are related to this technique, such as lymphedema and nerve damage. In addition, its clinical role is controversial. For this reason, the sentinel lymph node (SLN) has found increasing use in clinical practice over time. Oncologic safety, however, is debated, and there is no clear evidence in the literature regarding this. Therefore, our meta-analysis aims to schematically analyze the current scientific evidence to investigate the non-inferiority of SLN versus PLND regarding oncologic outcomes. Materials and Methods : Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in June 2022 since their early first publications. We made no restrictions on the country. We considered only studies entirely published in English. We included studies containing Disease-Free Survival (DFS), Overall Survival (OS), Recurrence Rate (RR), and site of recurrence data. We used comparative studies for meta-analysis. We registered this meta-analysis to the PROSPERO site for meta-analysis with protocol number CRD42022316650. Results : Twelve studies fulfilled inclusion criteria. The four comparative studies were enrolled in meta-analysis. Patients were analyzed concerning Sentinel Lymph Node Biopsy (SLN) and compared with Bilateral Pelvic Systematic Lymphadenectomy (PLND) in early-stage Cervical Cancer (ECC). Meta-analysis highlighted no differences in oncological safety between these two techniques, both in DFS and OS. Moreover, most of the sites of recurrences in the SLN group seemed not to be correlated with missed lymphadenectomy. Conclusions : Data in the literature do not seem to show clear oncologic inferiority of SLN over PLND. On the contrary, the higher detection rate of positive lymph nodes and the predominance of no lymph node recurrences give hope that this technique may equal PLND in oncologic terms, improving its morbidity profile.

Ronsini, C., et al. (2023). "The Efficiency of Sclerotherapy for the Management of Endometrioma: A Systematic Review and Meta-Analysis of Clinical and Fertility Outcomes." Medicina (Kaunas, Lithuania) 59(9).
	Background and Objectives : The most common sites of implantation of endometriotic tissue are the ovaries. Endometriomas are present in most cases of endometriosis (up to 45%). Although laparoscopic cystectomy is the standard of care in endometrioma, new strategies have been set up to minimize iatrogenic injuries to ovarian tissue. Sclerotherapy consists of injecting alcohol into the endometrioma to denature the amino acidic components of its pseudocapsule. The aim of this systematic review and meta-analysis is to compare clinical and pregnancy outcomes in surgery and sclerotherapy. Materials and Methods : Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched PubMed, EMBASE, Scopus, Google Scholar, Clinical-trials.gov, and the Cochrane Central Register of Controlled Trials databases in January 2023, adopting the string "Endometriosis and sclerotherapy". We made no limitations on the country and year of publication. We included the studies containing Success Rate (SR), Recurrence Rate (RR), Pregnancy Rate (PR) before and after the procedure. We used comparative studies for meta-analysis. Results : A total of 29 studies fulfilled inclusion criteria, 7 retrospective observational studies and 22 prospective studies. Eight comparative studies were enrolled in meta-analysis. Patients were analyzed concerning the number of recurrences and pregnancies in surgery, and compared with sclerotherapy. Four studies showed SR > 80.0%, and only two had SR < 80.0%, of which one consisted of tetracycline instillation. Only 1 study had 100% PR, the other 14 reported PR > 30.0%, whereas six had PR < 30.0%, of which one showed 0.0% PR with ethanol injection at two-thirds of the cyst fluid volume. Meta-analysis highlighted a non-significant lower incidence of recurrence in the surgery group compared to the sclerotherapy group ( p = 0.87). In parallel, the surgery group showed a non-significant better PR than the sclerotherapy group ( p = 0.08). Conclusions : Despite sclerotherapy having a minor incidence of postoperative complications compared to surgery, the latter is associated with a lower RR and better PR. However, those data assert the importance of a targeted therapy according to preoperative conditions and reproductive potential.

Ronsini, C., et al. (2023). "Radiotherapy and Chemotherapy Features in the Treatment for Locoregional Recurrence of Endometrial Cancer: A Systematic Review." Journal of Personalized Medicine 13(6).
	Radiation therapy (RT) is the standard of care in patients with locoregional or isolated vaginal recurrence who never underwent irradiation. It is often associated with brachytherapy (BT), whereas chemotherapy (CT) is a rare treatment option. We systematically searched the PubMed and Scopus databases in February 2023. We included patients with relapsed endometrial cancer, describing the treatment of locoregional recurrence, and reporting at least one outcome of interest-disease-free survival (DFS), overall survival (OS), recurrence rate (RR), site of recurrence, and major complications. A total of 15 studies fulfilled the inclusion criteria. Overall, 11 evaluated RT only, 3 evaluated CT, and 1 analyzed oncological outcomes after administration with a combination of CT and RT. In total, 4.5-year OS ranged from 16% to 96%, and DFS ranged from 36.3% to 100% at 4.5 years. RR ranged from 3.7% to 98.2% during a median follow-up of 51.5 months. Overall, RT showed a 4.5-year DFS from 40% to 100%. CT revealed 36.3% DFS at 4.5 years. RT showed a 4.5-year OS ranging from 16% to 96%, whereas CT revealed a 27.7% OS rate. It would be appropriate to test multi-modality regimens to evaluate outcomes and toxicity. EBRT and BT are the most employed options to treat vaginal recurrences.

Ronsini, C., et al. (2022). "Corrigendum to "Laparo-assisted vaginal radical hysterectomy as a safe option for minimal invasive surgery in early stage cervical cancer: A systematic review and meta-analysis" [Gynecologic Oncology Volume 166, Issue 1, July 2022, Pages 188195]." Gynecologic Oncology 167(2): 390-391.
	
Ronsini, C., et al. (2022). "Laparo-assisted vaginal radical hysterectomy as a safe option for minimal invasive surgery in early stage cervical cancer: A systematic review and meta-analysis." Gynecologic Oncology.
	Background: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it.; Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included.; Results: 18 studies fulfilled inclusion criteria. 8 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3033 patiets were included. Meta-analysis highlighted a non-statistic significant difference between LARVH and ARH (RR 0.82 [95% CI 0.55-1.23] p = 0.34; I 2 = 0%; p = 0.96). OS was feasible only for 3 studies (RR 1.14 [95% CI 0.28-4.67] p = 0.43; I 2 = 0 p = 0.86). Data about the type of recurrences (loco-regional vs distant) were collected.; Conclusion: LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.; Competing Interests: Declaration of Competing Interest The authors made no disclosures. No specific funding was disclosed. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ronsini, C., et al. (2022). "Erratum: Laparo-assisted vaginal radical hysterectomy as a safe option for minimal invasive surgery in early stage cervical cancer: A systematic review and meta-analysis (Gynecologic Oncology (2022) 166(1) (188-195), (S0090825822002517), (10.1016/j.ygyno.2022.04.010))." Gynecologic Oncology.
	Background: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. Method(s): Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. Result(s): 18 studies fulfilled inclusion criteria. 8 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3033 patiets were included. Meta-analysis highlighted a non-statistic significant difference between LARVH and ARH (RR 0.82 [95% CI 0.55-1.23] p = 0.34; I2 = 0%; p = 0.96). OS was feasible only for 3 studies (RR 1.14 [95% CI 0.28-4.67] p = 0.43; I2 = 0 p = 0.86). Data about the type of recurrences (loco-regional vs distant) were collected. Conclusion(s): LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.Copyright © 2022 Elsevier Inc.

Ronsini, C., et al. (2022). "Oncological outcomes in fertility-sparing treatment in stage IA-G2 endometrial cancer." Frontiers in Oncology 12: 965029.
	Background: The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins.; Study Design: Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA".; Results: A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months.; Conclusions: Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Ronsini, Mosca, Iavarone, Nicoletti, Vinci, Carotenuto, Pasanisi, Solazzo, De Franciscis, Torella, La Verde, Colacurci, Cobellis, Vizzielli and Restaino.)

Ronsini, C., et al. (2023). "Laparoscopic uterosacral ligament suspension: a systematic review and meta-analysis of safety and durability." Frontiers in surgery 10: 1180060.
	INTRODUCTION: Pelvic organ prolapse (POP) is a widespread condition affecting from 40% to 60% of women. Reconstructive vaginal surgeries are the most commonly performed procedures to treat POP. Among those, uterosacral ligament suspension (USLS), which is usually performed transvaginally, preserves pelvic statics and dynamics and appears to be an effective method. Laparoscopic USLS is a valid alternative to vaginal approach, and the aim of our review is to confirm its safety and feasibility and to compare clinical outcomes among the procedures. MATERIALS AND METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in December 2022. We made no restriction on the publication year nor on the country. Data about POP-Q recurrence rate (RR), intraoperative and postoperative complications (graded according to Clavien-Dindo classification), readmission rate, and reoperation rate were collected and analyzed. We used comparative studies for meta-analysis. RESULTS: A total of nine studies fulfilled inclusion criteria: two articles were non-comparative retrospective observational studies, three more articles were comparative studies where laparoscopic USLS was confronted with other surgical techniques (only data of laparoscopic USLS were analyzed), and four were comparative retrospective cohort studies between laparoscopic and vaginal USLS procedures. The comparative studies were enrolled in meta-analysis. Patients were analyzed concerning perioperative risks and the risk of recurrence. The meta-analysis highlighted that there was no clear inferiority of one technique over the other. DISCUSSION: Laparoscopic USLS is a technique with a low complication rate and low recurrence rate. Indeed, laparoscopic procedure allows better identification of anatomical landmarks and access to retroperitoneum. Moreover, efficacy over time and durability of Laparoscopic (LPS) USLS was also observed. However, these data should be weighed in light of the length of follow-up, which was in a very short range. Further, focused and prospective studies will be necessary to confirm this finding.

Ronsini, C., et al. (2023). "Mininvasive Cytoreduction Surgery plus HIPEC for Epithelial Ovarian Cancer: A Systematic Review." Medicina (Kaunas, Lithuania) 59(3).
	Background and objectives: The Gold-Standard treatment for Advanced Epithelial Ovarian Cancer remains cytoreductive surgery followed by systemic chemotherapy. Surgery can be performed either by an open or minimally invasive approach (MIS), although the former remains the most widely used approach. Recently, Van Driel et al. proved that adding 100 mg/m 2 of Cisplatin in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Interval Debulking Surgery (IDS) gives a disease-free survival (DFS) advantage. Similarly, Gueli-Alletti et al. demonstrated how the MIS approach is feasible and safe in IDS. Moreover, Petrillo et al. reported pharmacokinetic profiles with a higher chemotherapy concentration in patients undergoing HIPEC after MIS compared with the open approach. Therefore, the following review investigates the oncological and clinical safety consequences of the association between MIS and HIPEC. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in April 2022. Studies containing data about oncological and safety outcomes were included. We registered the Review to the PROSPERO site for meta-analysis with protocol number CRD42022329503. Results: Five studies fulfilled inclusion criteria. 42 patients were included in the review from three different Gynecological Oncological referral centers. The systematic review highlighted a Recurrence Rate ranging between 0 and 100%, with a 3-year Platinum-Free Survival between 10 and 70%. The most common HIPEC drug was Cisplatin, used at concentrations between 75 and 100 mg/m 2 and at an average temperature of 42 °C, for 60 to 90 min. Only 1 Acute Kidney Insufficiency has been reported. Conclusions: The scarcity of clinical trials focusing on a direct comparison between MIS and the open approach followed by HIPEC in EOC treatment does not make it possible to identify an oncological advantage between these two techniques. However, the safety profiles shown are highly reassuring.

Ronsini, C., et al. (2023). "Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 12(11).
	Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.

Ronsini, C., et al. (2022). "Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: A Problem with a Thousand Nuances-A Systematic Review of Oncological Outcomes." Annals of Surgical Oncology 29(13): 8346-8358.
	Background: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC). The guidelines have recognized various approaches, depending on the tumor stage and other risk factors such as histotype and lymphovascular positivity. Much more debate has centered around the boundary within which these treatments should be considered. Indeed, these are methods to be reserved for ECC, but tumor size may represent the most significant limitation. In particular, there is no consensus on the strategy to be adopted in the case of ECC ≥ 2 cm. Therefore, this systematic review was to collect the literature evidence regarding the management of these patients.; Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the Pubmed and Scopus databases was conducted in April 2022, from the date of the first publication. We made no limitation on the country. We included all studies containing data on disease-free survival, overall survival, recurrence rate (RR), or complete response rate (CRR) to chemotherapy.; Results: Twenty-six studies fulfilled the inclusion criteria, and 691 patients were analyzed regarding FST. Surgery-based FST showed an RR of between 0 and 42.9%, which drops to 12.9% after excluding the vaginal or minimally invasive approaches. Furthermore, papers regarding FST based on the neoadjuvant chemotherapy (NACT) approach showed a CRR of between 21.4 and 84.5%, and an RR of between 0 and 22.2% CONCLUSION: This paper focused on the significant heterogeneity present in the clinical management of FST of ECC ≥ 2 cm. Nevertheless, from an oncological point of view, approaches limited to the minimally invasive or vaginal techniques showed the highest RR. Vice versa, the lack of standardization of NACT schemes and the wealth of confounders to be attributed to the histological features of the tumor make it difficult, if not impossible, to set a standard of treatment. (© 2022. The Author(s).)

Ronsini, C., et al. (2023). "Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes." Annals of Surgical Oncology 30(9): 5587-5596.
	Background: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm.; Methods: A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates.; Results: Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001).; Conclusion: Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise. (© 2023. The Author(s).)

Roozbeh, N., et al. (2019). "Effect of Lavender on Sleep, Sexual Desire, Vasomotor, Psychological and Physical Symptom among Menopausal and Elderly Women: A Systematic Review." Journal of Menopausal Medicine 25(2): 88-93.
	OBJECTIVES: The present systematic review was conducted to compare the effect of lavender on the quality of sleep, sexual desire, and vasomotor, psychological and physical symptoms among menopausal and elderly women. METHODS: There were five electronic databases which selected to search respective articles which included were Scopus, PubMed, Web of Science, Google Scholar, and the Cochrane Library without any language restriction since the study inception to March 10, 2018. The quality of studies was assessed in accordance with a jaded scale. RESULTS: According to three trials, the lavender as utilized in a capsule form or aromatherapy could significantly improve the measured Pittsburgh Sleep Quality Index score (P < 0.05) in the menopausal and elderly women. The aromatherapy with lavender improved sexual function (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), and physical (P < 0.001) symptoms. Based on a trial, 66.7%, 70.0%, and 53.3% of subjects reported feelings of relaxation, happiness, and cleanness effects of having used lavender respectively. CONCLUSIONS: The results suggested the effectiveness of the use of lavender either in capsule form or aromatherapy on the improved quality of sleep, depression, anxiety, sexual desire, and psychological and physical symptoms. These results, however, should be interpreted with caution considering the limitations of the study.

Roque, D., et al. (2021). "Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer." Gynecologic Oncology 162: S58.
	Objectives: Ixabepilone is a microtubule‐stabilizing agent that may retain activity in paclitaxel‐treated patients. The goal of this multicenter randomized phase II study was to assess the activity and safety of ixabepilone with bevacizumab compared to ixabepilone alone in patients with platinum‐resistant/refractory ovarian, fallopian tube, or primary peritoneal cancer. An exploratory objective was to examine the role of prior treatment with bevacizumab and tumor expression of class III ß‐tubulin (TUBB3) by immunohistochemistry as a predictive biomarker. Methods: Participants were randomly assigned to receive ixabepilone 20 mg/m2 days 1, 8, 15 with (IXA+BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by receipt of prior BEV. The primary endpoint was progression‐free survival (PFS). Overall survival (OS), safety, and response rates served as secondary endpoints.[Formula presented] Results: A total of 78 patients were randomized from March 2017‐July 2020. Among 76 evaluable patients who received IXA+BEV (n=39) compared to IXA (n=37), the objective response rate was 33% (n=13) versus 8% (n=3) (P=0.004), with clinical benefit durable at 6 months in 37% (n=14) and 3% (n=1) (P<0.001). The addition of BEV significantly improved both PFS (median 5.5 vs 2.2 months, HR=0.33, 95% CI 0.19‐0.55, P<0.001) [Fig. 1a] and OS (median 10.0 vs 6.0 months, HR=0.52, 95% CI 0.31‐0.87, P=0.006) [Fig. 1b]. Both regimens were well‐tolerated. TUBB3 expression did not predict response in either arm. Subgroup analyses revealed minimal effect of prior BEV on response to IXA+BEV [Fig 1c/d]. Conclusions: IXA+BEV is a well‐tolerated, effective combination for treatment of platinum/taxane‐resistant/refractory ovarian cancer that extends both PFS/OS relative to IXA monotherapy. Prior receipt of BEV should not preclude use of IXA+BEV. TUBB3 is not a predictive biomarker for response to IXA+BEV.

Roque, D. M., et al. (2024). "Correction to: Randomised phase II trial of weekly ixabepilone+/-biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (British Journal of Cancer, (2022), 126, 12, (1695-1703), 10.1038/s41416-022-01717-6)." British Journal of Cancer.
	Correction to: British Journal of Cancerhttps://doi.org/10.1038/s41416-022-01717-6, published online 11 February 2022 The article "Randomised phase II trial of weekly ixabepilone +/- biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer", written by Dana M. Roque, Eric R. Siegel, Natalia Buza, Stefania Bellone, Dan-Arin Silasi, Gloria S. Huang, Vaagn Andikyan, Mitchell Clark, Masoud Azodi, Peter E. Schwartz, Gautam G. Rao, Jocelyn C. Reader, Pei Hui, Joan R. Tymon-Rosario, Justin Harold, Dennis Mauricio, Burak Zeybek, Gulden Menderes, Gary Altwerger, Elena Ratnerand and Alessandro D. Santin, was originally published electronically on the publisher's internet portal on 11 February 2022 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 21 January 2024 to © The Authors 2024 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ The original article has been corrected.Copyright © The Author(s) 2024.

Roque, M., et al. (2019). "Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes." Human Reproduction Update 25(1): 2-14.
	Background: Elective freezing of all good quality embryos and transfer in subsequent cycles, i.e. elective frozen embryo transfer (eFET), has recently increased significantly with the introduction of the GnRH agonist trigger protocol and improvements in cryo-techniques. The ongoing discussion focuses on whether eFET should be offered to the overall IVF population or only to specific subsets of patients. Until recently, the clinical usage of eFET was supported by only a few randomized controlled trials (RCT) and meta-analyses, suggesting that the eFET not only reduced ovarian hyperstimulation syndrome (OHSS), but also improved reproductive outcomes. However, the evidence is not unequivocal, and recent RCTs challenge the use of eFET for the general IVF population.; Objective and Rationale: This systematic review and meta-analysis aimed at evaluating whether eFET is advantageous for reproductive, obstetric and perinatal outcomes compared with fresh embryo transfer in IVF/ICSI cycles. Additionally, we evaluated the effectiveness of eFET in comparison to fresh embryo transfer in different subgroups of patients undergoing IVF/ICSI cycles.; Search Methods: We conducted a systematic review, using PubMed/Medline and EMBASE to identify all relevant RCTs published until March 2018. The participants included infertile couples undergoing IVF/ICSI with or without preimplantation genetic testing for aneuploidy (PGT-A). The primary outcome was the live birth rate (LBR), whereas secondary outcomes were cumulative LBR, implantation rate, miscarriage, OHSS, ectopic pregnancy, preterm birth, pregnancy-induced hypertension, pre-eclampsia, mean birthweight and congenital anomalies. Subgroup analyses included normal and hyper-responder patients, embryo developmental stage on the day of embryo transfer, freezing method and the route of progesterone administration for luteal phase support in eFET cycles.; Outcomes: Eleven studies, including 5379 patients, fulfilling the inclusion criteria were subjected to qualitative and quantitative analysis. A significant increase in LBR was noted with eFET compared with fresh embryo transfer in the overall IVF/ICSI population [risk ratio (RR) = 1.12; 95% CI: 1.01-1.24]. Subgroup analyses indicated higher LBRs by eFET than by fresh embryo transfer in hyper-responders (RR = 1.16; 95% CI: 1.05-1.28) and in PGT-A cycles (RR = 1.55; 95% CI: 1.14-2.10). However, no differences were observed for LBR in normo-responders (RR = 1.03; 95% CI: 0.91-1.17); moreover, the cumulative LBR was not significantly different in the overall population (RR = 1.04; 95% CI: 0.97-1.11). Regarding safety, the risk of moderate/severe OHSS was significantly lower with eFET than with fresh embryo transfer (RR = 0.42; 95% CI: 0.19-0.96). In contrast, the risk of pre-eclampsia increased with eFET (RR = 1.79; 95% CI: 1.03-3.09). No statistical differences were noted in the remaining secondary outcomes.; Wider Implications: Although the use of eFET has steadily increased in recent years, a significant increase in LBR with eFET was solely noted in hyper-responders and in patients undergoing PGT-A. Concerning safety, eFET significantly decreases the risk of moderate and severe OHSS, albeit at the expense of an increased risk of pre-eclampsia.

Rosa, M.-M. and F. Christina (2021). "Adjuvant treatment in primary setting and recurrence disease in low grade serous ovarian cancer: systematic review of literature and meta-analysis."
	
Rosato, R., et al. (2024). "Impact of different follow-up regimens on health-related quality of life and costs in endometrial cancer patients: Results from the TOTEM randomized trial." Gynecologic Oncology 184: 150-159.
	Purpose: To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival. Method(s): In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints. Result(s): 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was 531 for low-risk patients and 683 for high-risk patients. Conclusion(s): In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention.Copyright © 2024 The Authors

Rose, G. L., et al. (2023). "Efficacy of exercise interventions for women during and after gynaecological cancer treatment - a systematic scoping review." Supportive Care in Cancer 31(6): 342.
	Purpose: To systematically synthesise evidence of exercise intervention efficacy for physical/psychosocial outcomes that matter to women during/following treatment for gynaecological cancer. Method(s): Five databases were searched (PubMed, EMBASE, CINAHL, PsychInfo, Scopus). Exercise-only intervention studies that included women during/ following treatment for any gynaecological cancer, with/ without control comparison, on any physical or psychosocial outcome(s), were included and qualitatively appraised using the Revised Cochrane Risk of Bias tool and a modified Newcastle-Ottawa Scale. Result(s): Seven randomised controlled trials (RCTs), three single-arm pre-post studies, and one prospective cohort study satisfied were included (11 studies). Most studies were completed following treatment (91%), included combined (aerobic and resistance; 36%) and aerobic (36%) training, were fully/mostly (63%) unsupervised, and had a moderate-to-high risk of bias. Overall, 33 outcomes (64% objectively-measured) were assessed. Improvements were observed in aerobic capacity (VO2 Peak +1.6 mL/kg/min, 6-minute walk distance +20-27 m), lower- (30-second sit-to-stand +2-4 repetitions) and upper-limb strength (30-second arm curl +5 repetitions; 1RM grip strength/chest press +2.4-3.1 kg), and agility (timed up-and-go -0.6 seconds). However, changes in quality of life, anthropometry/body composition, balance and flexibility were inconsistent. There was no evidence to support worsening of outcomes. Conclusion(s): Preliminary research into the role of exercise post-gynaecological cancer suggests an improvement in exercise capacity, muscular strength, and agility which, in the absence of exercise, typically decline following gynaecological cancer. Future exercise trials involving larger and more diverse gynaecological cancer samples will improve understanding of the potential and magnitude of effect of guideline-recommended exercise on outcomes that matter to patients.Copyright © 2023, The Author(s).

Röseler, J., et al. (2021). "Challenges and Controversies in the Surgical Treatment of Cervical Cancer: Open Radical Hysterectomy versus Minimally Invasive Radical Hysterectomy." Journal of Clinical Medicine 10(17).
	Objective: The aim of the study was to perform a systematic assessment of disease-free survival (DFS), overall survival, and morbidity rates after open radical hysterectomy (ORH) and minimally invasive surgery (MIS) for early-stage cervical cancer and discuss with experts the consequences of the LACC trial (published by Ramirez et al. in 2018) on clinical routine.; Methods: A total of 5428 records were retrieved. After exclusion based on text screening, four records were identified for inclusion. Five experts from three independent large-volume medical centers in Europe were interviewed for their interpretation of the LACC trial.; Results: The LACC trial showed a significantly higher risk of disease progression with MIS compared to ORH (HR 3.74, 95% CI 1.63 to 8.58). This was not seen in one epidemiological study and was contradicted by one prospective cohort study reported by Greggi et al. A systematic review by Zhang et al. mentioned a similar DFS for robot-assisted radical hysterectomy (RRH) and LRH. Recurrence rates were significantly higher with MIS compared to ORH in the LACC trial (HR 4.26, 95% CI 1.44 to 12.60). In contrast, four studies presented by Greggi reported no significant difference in recurrence rates between LRH/RRH and ORH, which concurred with the systematic reviews of Zhang and Zhao. The experts mentioned various limitations of the LACC trial and stated that clinicians were obliged to provide patients with detailed information and ensure a shared decision-making process.; Conclusions: The surgical treatment of early-stage cervical cancer remains a debated issue. More randomized controlled trials (RCT) will be needed to establish the most suitable treatment for this condition.

Roshandel, H. S., et al. (2022). "Herbal medicine in treatment of dysmenorrhea: a systematic review." TMR Integrative Medicine 6: e22023.
	Objective: Herbal medicine has been a standard treatment for primary dysmenorrhea in different cultures and countries, and multiple studies have shown its possible positive effect on pain relief. This systematic review of the literature was conducted to assess different types of herbal medicine used to treat primary dysmenorrhea and evaluate the effectiveness of these medicines. Method(s): This study systematically reviewed published articles on herbal medicine treating primary dysmenorrhea for 10 years (2011-2021), using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In February 2022, international credible scholarly databases were searched. Also, the references of selected articles were hand searched to find relevant studies. Based on the search syntax, the search guideline was first defined for the PubMed database and was later revised according to each database's specific framework of search method. The studies were included if they were either clinical trials or Quasi-Experimental, published in English or Persian between 2011 to 2021. Grey literature, unfinished studies, and studies without well-defined primary dysmenorrheal participants were excluded. Result(s): Seventy-three studies investigated the effectiveness of a total of 44 plants and plant combinations (35 single plants and 9 combinations of plants) on primary dysmenorrhea of which only one study did not report a significant positive effect. Ginger was the most investigated plant. Eight studies assessed the effects of ginger alone, and four studied the combination of ginger with other plants, all of them showed significant effects but one study. Nine studies investigated the effects of either fennel or its combination, five studies were on chamomile and three studies were related to lavender. Overall, all of them, except one, reported the positive effect of herbal medicine on primary dysmenorrhea. Conclusion(s): Different herbal medicine has been used to treat primary dysmenorrhea, significantly reducing pain intensity or duration or bleeding severity or duration.Copyright © 2022 By Author(s). Published by TMR Publishing Group Limited. This is an open access article under the CC-BY license. (https://creativecommons.org/licenses/by/4.0/)

Rosielle, K., et al. (2022). "Oil-based versus water-based contrast media for hysterosalpingography in infertile women of advanced age, with ovulation disorders or a high risk for tubal pathology: study protocol of a randomized controlled trial (H2Oil2 study)." BMC Women's Health 22(1): 123.
	Background: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography (HSG) increases ongoing pregnancy and subsequent live birth rates when compared to tubal flushing with water-based contrast. It is currently unclear whether an HSG with oil-based contrast also results in more ongoing pregnancies and live births in women of advanced age, women with ovulation disorders, and women with potential tubal pathology when compared to an HSG with water-based contrast.; Methods: We plan an international, multicentre, open-label, randomized controlled trial (RCT) studying three groups of infertile women who have an indication for tubal patency testing according to their treating physician and additionally; (1) are 39 years of age or older, (2) have an ovulation disorder or (3) have a high risk for tubal pathology based on their medical history. Women with an allergy for iodinated contrast medium are excluded, as are women with diabetes, hyperprolactinemia or untreated hyper- or hypothyroidism, and women with a partner with severe male infertility. After informed consent, women will be randomly allocated to the intervention, tubal flushing with the use of oil-based contrast during HSG or the control group, tubal flushing with the use of water-based contrast during HSG in a 1:1 ratio by the web-based system Castor. The primary endpoint will be ongoing pregnancy leading to live birth with conception within six months after randomization. Secondary outcomes are other pregnancy outcomes, used fertility treatments, adverse events and cost-effectiveness. Based on the expected ongoing pregnancy rate of 17% in the control group and 27% in the intervention group, the sample size will be 930 women (465 per group). Study inclusion is expected to be complete in four years.; Discussion: This multicentre RCT will establish whether, for women of advanced age, women with ovulatory disease, and women who have a high risk for tubal pathology, there is a fertility enhancing effect of tubal flushing with oil-based contrast during HSG and whether the use of this contrast medium is cost-effective. Trial Registration The study was prospectively registered in the Netherlands Trial Register on August 1st 2019 as 'H2Oil2' (reference number NL7925, https://www.trialregister.nl/trial/7925 ). (© 2022. The Author(s).)

Ross, C. (2022). "Estrogen treatments and risk of Alzheimer's disease: A systematic review." Dissertation Abstracts International: Section B: The Sciences and Engineering 83(2-B): No-Specified.
	Background: Since the publication of the Women's Health Initiative (WHI) trials, prescription of hormone therapy (HT) for menopausal women have declined. With interest on the potential benefits of HT being renewed, more researchers have examined its effects on cognition and risk of developing Alzheimer's Disease (AD). Objective: This systematic review was conducted to synthesize data regarding the use of HT during menopausal transition and its relationship with the risk of AD. Methods: A systematic literature search was conducted using the databases PubMed, Web of Science, and Google Scholar. Results: 40 articles were included in the review based on inclusion and exclusion criteria. The studies focused on themes of AD trends, biological mechanisms of AD, menopausal transition, menopause management, and effects of estrogen treatment. Conclusion: Generally, results from the studies have indicated potential cognitive benefits of estrogen, and in turn HT, on women in menopausal transition who are at risk for AD. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Ross Jonathan, D. C., et al. (2023). "Intravaginal lactic acid gel versus oral metronidazole for treating women with recurrent bacterial vaginosis: the VITA randomised controlled trial." BMC Women's Health 23(1): 241.
	Background: Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis.; Methods: We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥ 16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400 mg twice daily oral metronidazole tablets or 5 ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects.; Results: Five hundred and eighteen participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively).; Conclusions: Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects.; Trial Registration: ISRCTN14161293 , prospectively registered on 18 th September 2017. (© 2023. The Author(s).)

Rottey, S., et al. (2022). "Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors." Clinical Cancer Research 28(1): 95-105.
	Purpose: To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody-drug conjugate (ADC)+/-nivolumab, in patients with selected tumors. Patients and Methods: In an international phase I/IIa study [NCT02341625 (CA008-002)], patients received BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n=96) or BMS-986148 0.8 mg/kg nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability. Result(s): In CA008-002, the most common (>= 10%) treatmentrelated adverse events (TRAEs) included increased aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 every 3 weeks monotherapy, three (25%) receiving BMS-986148 once-weekly monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab every 3 weeks. Overall, 17 of 126 patients (13%) discontinued because of a TRAE. The MTD of BMS-986148 was 1.2 mg/kg i.v. every 3 weeks. The safety profile of BMS-986148 nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (every 3 weeks and once weekly). Preliminary clinical activity was observed with BMS-986148 +/- nivolumab. No association between mesothelin expression and response was detected. Conclusion(s): BMS-986148 _ nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors.Copyright © 2022 American Association for Cancer Research Inc.. All rights reserved.

Rountis, A., et al. (2021). "The Role of Laparoscopic Surgery in the Treatment of Advanced Uterine Prolapse: A Systematic Review of the Literature." Cureus 13(9): e18281.
	The aim of this review is to investigate and compare all laparoscopic techniques that can be used in the surgical repair of advanced uterine prolapse. A systematic search of the PubMed, Scopus, Cochrane CENTRAL, and Clinicaltrials.gov databases was performed for articles published up to December 2020, reporting data on the treatment of severe uterine prolapse using laparoscopic procedures. Only studies in the English language, with a patient sample of ≥20 and a follow-up time of ≥12 months were included. The final synthesis of this review consisted of six studies. The main laparoscopic procedures reported were vaginally assisted laparoscopic sacrocolpopexy, vaginally assisted laparoscopic uterine sacropexy, laparoscopic sacrocolpopexy with laparoscopic supracervical hysterectomy, laparoscopic inguinal ligament suspension with uterine preservation, and laparoscopic uterosacral ligament suspension combined with trachelectomy. All procedures involved mesh placement, except for laparoscopic uterosacral ligament suspension. All procedures reported anatomical cure rates > 90%. Vaginally assisted laparoscopic sacrocolpopexy had the largest amount of intraoperative blood loss whilst vaginally assisted laparoscopic uterine sacropexy was associated with bladder injuries intraoperatively. All vaginally assisted procedures reported cases of mesh extrusion postoperatively. Laparoscopic inguinal ligament suspension was the operation with the longest mean operative and hospitalization time. Conversions were not reported. The present study shows that minimally invasive surgery can be used efficiently as an alternative to open surgery in the treatment of severe uterine prolapse.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2021, Rountis et al.)

Rovelli Richard, J., et al. (2022). "Systematic review of oral pharmacotherapeutic options for the management of uterine fibroids." Journal of the American Pharmacists Association : JAPhA 62(3): 674.
	Background: Uterine fibroids constitute a significant health problem in the United States, affecting upward of 11 million people.; Objective: Characterize the literature regarding the incidence of amenorrhea and reductions in abnormal uterine bleeding and fibroid size and to report on clinically relevant safety outcomes of oral medications that may be used to manage symptomatic uterine fibroids to assist in choice of therapeutic options.; Methods: A literature search was conducted through December 31, 2021, using Embase, MEDLINE, and International Pharmaceutical Abstracts databases. Primary literature reporting on safety or efficacy data of any oral medication for the treatment of symptomatic uterine fibroids was included. Relevant study characteristics, outcomes, and safety data were extracted. Data extraction was performed in duplicate with any discordant data reconciled by the entire investigative team.; Results: A total of 41 studies met inclusion criteria-28 randomized control trials (RCTs), 11 prospective observational studies, 1 phase-1 pharmacokinetic study, and 1 pooled study. The majority of literature involved the study of mifepristone (n = 26, [63.4%]), followed by vilaprisan (n = 5, [12.2%]), elagolix (n = 5, [12.2%]), relugolix (n = 4, [9.8%]), and linzagolix (n = 1 [2.4%]). A total of 33 articles (80.5%) reported results pertaining to the efficacy objectives of this review with all medications statistically significantly improving at least one of these domains. Hot flashes, liver function test abnormalities, and endometrial hyperplasia were the most often reported adverse events. Of the RCTs, 7 of 28 (25%) had a moderate-high risk of bias (RoB), whereas 10 of 11 (90.9%) observational studies had a moderate-high RoB. The majority of moderate-high RoB studies involved the study of mifepristone (15 of 18, 83.3%).; Conclusions: Given higher quality of evidence, confirmed therapeutic efficacy, and a milder adverse effect profile, the contemporary gonadotropin releasing hormone antagonists (elagolix, relugolix, linzagolix) and vilaprisan represent preferred oral treatment options for the management of uterine fibroids. (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Rovere, G., et al. (2021). "Epidemiology and aetiology of male and female sexual dysfunctions related to pelvic ring injuries: a systematic review." International Orthopaedics 45(10): 2687-2697.
	Introduction: Pelvic ring injuries, frequently caused by high energy trauma, are associated with high rates of morbidity and mortality (5-33%), often due to significant blood loss and disruption of the lumbosacral plexus, genitourinary system, and gastrointestinal system. The aim of the present study is to perform a systematic literature review on male and female sexual dysfunctions related to traumatic lesions of the pelvic ring. Method(s): Scopus, Cochrane Library MEDLINE via PubMed, and Embase were searched using the keywords: "Pelvic fracture," "Pelvic Ring Fracture," "Pelvic Ring Trauma," "Pelvic Ring injury," "Sexual dysfunction," "Erectile dysfunction," "dyspareunia," and their MeSH terms in any possible combination. The following questions were formulated according to the PICO (population (P), intervention (I), comparison (C), and outcome (O)) scheme: Do patients suffering from pelvic fracture (P) report worse clinical outcomes (C), in terms of sexual function (O), when urological injury occurs (I)? Is the sexual function (O) influenced by the type of fracture (I)? Results: After screening 268 articles by title and abstract, 77 were considered eligible for the full-text analysis. Finally 17 studies that met inclusion criteria were included in the review. Overall, 1364 patients (902 males and 462 females, M/F ratio: 1.9) suffering from pelvic fractures were collected. Discussion(s): Pelvic fractures represent challenging entities, often concomitant with systemic injuries and subsequent morbidity. Anatomical consideration, etiology, correlation between sexual dysfunction and genitourinary lesions, or pelvic fracture type were investigated. Conclusion(s): There are evidences in the literature that the gravity and frequency of SD are related with the pelvic ring fracture type. In fact, patients with APC, VS (according Young-Burgess), or C (according Tile) fracture pattern reported higher incidence and gravity of SD. Only a week association could be found between GUI and incidence and gravity of SD, and relationship between surgical treatment and SD. Electrophysiological tests should be routinely used in patient suffering from SD after pelvic ring injuries.Copyright © 2021, The Author(s).

Rubinstein Maria, M., et al. (2023). "Durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial cancer or endometrial carcinosarcoma: A randomized open-label phase 2 study." Gynecologic Oncology 169: 64-69.
	Introduction: Our understanding of the biologic heterogeneity of endometrial cancer has improved, but which patients benefit from single-agent versus combination immune checkpoint blockade remains unclear.; Methods: We conducted a single-center, randomized, open-label, phase 2 study of durvalumab 1500 mg (Arm 1) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks (Arm 2) in patients with endometrial carcinoma. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS) at 24 weeks. Patients were stratified by mismatch repair (MMR) status and carcinosarcoma histology. Using a Simon two-stage minimax design, we determined 40 patients per arm would provide 90% power and Type 1 error of 10%.; Results: Eighty-two patients were enrolled; 77 were evaluable for toxicity (Arm 1: 38, Arm 2: 39) and 75 evaluable for efficacy (Arm 1: 37, Arm 2: 38). Patient were stratified by MMR status (Arm 1: 5, Arm 2: 4 were MMR-deficient). The ORR in Arm 1 was 10.8% (one-sided 90% CI: 4.8-100%); the ORR in Arm 2 was 5.3% (one-sided 90% CI: 1.4-100%). Since the primary endpoint of ORR was not met, 24-week PFS was not compared to historical controls per protocol specification. No new safety signals were identified.; Conclusions: In these patients with predominantly MMR-proficient endometrial cancer, there was limited response with single-agent and combined immune checkpoint blockade. The pre-specified efficacy thresholds were not met for further evaluation. A deeper understanding of potential mechanisms of resistance to immunotherapy in MMR-proficient endometrial cancer is needed for the development of novel therapeutic approaches.; Competing Interests: Declaration of Competing Interest Dr. Rubinstein reports grant support paid to the institution from Merck, Zentalis, and AstraZeneca. Dr. Iasonos reports consulting fees from Mylan. Dr. Friedman reports grant support paid to the institution from Genentech/Roche, Bristol Myers Squibb (BMS), Merck, AstraZeneca, and Daiichi; consulting fees from Seagen and BMS; and waived compensation for advisory board participation from Merck and Genentech. Dr. O'Cearbhaill reports meeting/travel support from the Gynecologic Oncology Foundation, Curio, and Hitech Health; participation in the advisory boards of Tesaro/GlaxoSmithKline (GSK), Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, and CarinaBiotech (non-compensated); non-compensated steering committee participation for Tesaro/GSK and AstraZeneca; and grant support paid to the institution from Bayer/Celgene/Juno, Tesaro/GSK, Merck, the Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, KitePharma, and the Gynecologic Oncology Foundation. Dr. Cadoo reports grant support paid to the institution from The Irish Cancer Society, MSD, and Immunogen; consulting fees from Nextcure, MJH Life Sciences, and GSK; honoraria from SGK, AstraZeneca, and MSD; meeting/travel support from Roche, Pfizer, and MSD; and board/committee participation for MSD, AstraZeneca, GSK, Eisai, The National Cancer Control Programme Ireland (voluntary), and the ARC Cancer Support Centers (voluntary). Dr. Kyi reports grant support paid to the institution from Merus, Gritstone, and BMS; consulting fees from Scenic Immunology BV and OncLive; and meeting/travel support from the Conquer Cancer Foundation and Gritstone. Dr. Zamarin reports grant support paid to the institution from AstraZeneca, Roche, Plexxikon, and Synthekine; patents from Merck and Newcastle Disease Virus for Cancer Therapy; consulting fees from Memgen, Celldex, Agenus, Astellas, AstraZeneca, Crown Biosciences, Roche, GSK, Hookipa, ImmunOS, Kalivir, Synologic Therapeutics, Synthekine, Takeda, Targovax, Tessa Therapeutics, and Xencor; and stock options from Accurius Therapeutics, ImmunOS Therapeutics, and Calidi Biotherapeutics. Dr. Aghajanian reports grant support paid to the institution from Abbvie, Clovis, Genentech, and AstraZeneca; consulting fees from sai/Merck, Mersana Therapeutics, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation for Blueprint Medicine; and unpaid participation on the Board of Directors of the GOG Foundation and NRG Oncology. Dr. Billinson reports stock ownership in Abbvie and Johnson and Johnson. Dr. Makker reports unpaid board participation for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly and Immunocore. The authors have no potential conflicts of interest to disclose. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rudolph, J. E., et al. (2022). "Estimation of the Average Causal Effect in Longitudinal Data With Time-Varying Exposures: the Challenge of Nonpositivity and the Impact of Model Flexibility." American journal of epidemiology 191(11): 1962‐1969.
	There are important challenges to the estimation and identification of average causal effects in longitudinal data with time‐varying exposures. Here, we discuss the difficulty in meeting the positivity condition. Our motivating example is the per‐protocol analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial. We estimated the average causal effect comparing the incidence of pregnancy by 26 weeks that would have occurred if all women had been assigned to aspirin and complied versus the incidence if all women had been assigned to placebo and complied. Using flexible targeted minimum loss‐based estimation, we estimated a risk difference of 1.27% (95% CI: ‐9.83, 12.38). Using a less flexible inverse probability weighting approach, the risk difference was 5.77% (95% CI: ‐1.13, 13.05). However, the cumulative probability of compliance conditional on covariates approached 0 as follow‐up accrued, indicating a practical violation of the positivity assumption, which limited our ability to make causal interpretations. The effects of nonpositivity were more apparent when using a more flexible estimator, as indicated by the greater imprecision. When faced with nonpositivity, one can use a flexible approach and be transparent about the uncertainty, use a parametric approach and smooth over gaps in the data, or target a different estimand that will be less vulnerable to positivity violations.

Rudzinskas Sarah, A., et al. (2023). "Divergent Transcriptomic Effects of Allopregnanolone in Postpartum Depression." Genes 14(6).
	Brexanolone, a formulation of the neurosteroid allopregnanolone (ALLO), is approved for treating postpartum depression (PPD) and is being investigated for therapeutic efficacy across numerous neuropsychiatric disorders. Given ALLO's beneficial effects on mood in women with PPD compared to healthy control women, we sought to characterize and compare the cellular response to ALLO in women with ( n = 9) or without ( n = 10, i.e., Controls) past PPD, utilizing our previously established patient-derived lymphoblastoid cell lines (LCLs). To mimic in vivo PPD ALLO-treatment, LCLs were exposed to ALLO or DMSO vehicle for 60 h and RNA-sequenced to detect differentially expressed genes (DEGs, p nominal < 0.05). Between ALLO-treated Control and PPD LCLs, 269 DEGs were identified, including Glutamate Decarboxylase 1 ( GAD1 ), which was decreased 2-fold in PPD. Network analysis of PPD:ALLO DEGs revealed enriched terms related to synaptic activity and cholesterol biosynthesis. Within-diagnosis analyses (i.e., DMSO vs. ALLO) detected 265 ALLO-induced DEGs in Control LCLs compared to only 98 within PPD LCLs, with just 11 DEGs overlapping. Likewise, the gene ontologies underlying ALLO-induced DEGs in PPD and Control LCLs were divergent. These data suggest that ALLO may activate unique and opposing molecular pathways in women with PPD, which may be tied to its antidepressant mechanism.

Ruffolo, A. F., et al. (2022). "Vaginal Laser Therapy for Female Stress Urinary Incontinence: New Solutions for a Well-Known Issue-A Concise Review." Medicina (Kaunas, Lithuania) 58(4).
	Background and Objectives: Insufficient connective urethra and bladder support related to childbirth and menopausal estrogen decrease leads to stress urinary incontinence (SUI). The aim of this review is to narratively report the efficacy and safety of new mini-invasive solutions for SUI treatment as laser energy devices, in particular, the microablative fractional carbon dioxide laser and the non-ablative Erbium-YAG laser. Material(s) and Method(s): For this narrative review, a search of literature from PubMed and EMBASE was performed to evaluate the relevant studies and was limited to English language articles, published from January 2015 to February 2022. Result(s): A significant subjective improvement, assessed by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF) was reported at the 6-month follow up, with a cure rate ranged from 21% to 38%. A reduction of effect was evidenced between 6 and 24-36 months. Additionally, the 1-h pad weight test evidence a significant objective improvement at the 2-6-month follow up. Conclusion(s): SUI after vaginal laser therapy resulted statistically improved in almost all studies at short-term follow up, resulting a safe and feasible option in mild SUI. However, cure rates were low, longer-term data actually lacks and the high heterogeneity of methods limits the general recommendations. Larger RCTs evaluating long-term effects are required.

Ruixin, Z., et al. (2023). "Plant-based dietary patterns and female reproductive health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies."
	
Ruiz-Echeverría, F. R., et al. (2022). "Ovarian sex cord tumor with annular tubules: case report and review of the literature." Revista colombiana de obstetricia y ginecologia 73(3): 317-329.
	OBJECTIVES: To report a case of ovarian sex cord tumor with annular tubules (SCTAT) and conduct a literature review on diagnosis, treatment and prognosis of this condition. MATERIAL AND METHODS: Case report of a woman with a final diagnosis of advanced SCTAT seen at the National Cancer Institute in Bogota (Colombia) who received surgical treatment and chemotherapy with a satisfactory course after 6 months. A literature search was conducted in the Medline via PubMed, LILACS and Scielo databases, including case reports and series of women diagnosed with SCTAT published since 1990, not using age ranges. Information about diagnosis, treatment and reported prognosis was retrieved. A narrative summary of the findings was prepared. RESULTS: Fourteen publications with 26 patients were included. Mean age at diagnosis was 22.5 years. The main symptoms were menstruation abnormalities and pelvic pain. Computed tomography (CT) was the imaging technology most frequently used. Surgical treatment was used in all cases, together with chemotherapy in 29 %; 2 patients received radiotherapy. Recurrence occurred in 20 % of cases. Mortality was 12.5 %, with all deaths occurring within the first year. CONCLUSIONS: There is a paucity of information about the diagnostic utility of imaging, tumor markers and histochemical studies, as well as prognosis of this disease condition. Surgery is the treatment of choice, taking into consideration the patient’s wishes regarding fertility, as well as the stage of the tumor. Further studies are needed to provide more detailed information about this condition.

Ruizhe, L., et al. (2022). "Survival After Minimally Invasive Radical Hysterectomy Without the Use of Uterine Manipulator for Cervical Cancer: A Systematic Review and Meta-Analysis."
	
Ruiz-Rios, M. and S. Maldonado-Martin (2022). "Physical activity on cardiorespiratory fitness and cardiovascular risk in premenopausal and postmenopausal women: a systematic review of randomized controlled trials." Menopause (New York, N.Y.) 29(10): 1222-1229.
	Importance: The apparent cardioprotective effects of endogenous estrogens to prevent cardiovascular disease in premenopausal women are reduced with the loss of estrogen post-menopause. Cardiorespiratory fitness and cardiovascular risk factors are closely related to physical activity levels.; Objective: This study conducted a critical assessment of studies for health prevention that analyze the effects of physical activity programs on cardiorespiratory fitness and cardiovascular risk factors in women, comparing premenopausal and postmenopausal states, through a systematic review of randomized controlled trials.; Evidence Review: A computerized literature search was performed to include articles up until December 2021 in the following online databases: PubMed, Cochrane, Scopus, SportDiscus, and Web of Science. Regarding physical activity intervention, women of all ages were engaged. The PEDro scale and Oxford's evidence levels were used for the assessment of the risk of bias in the included articles.; Findings: Fourteen scientific articles met the inclusion criteria. Great variability was found in physical activity variables. All the studies found an improvement in at least one variable. The risk of bias was high, with all the articles obtaining a low methodological quality, except two with high methodological quality. Only one article considered the differences in the menopausal state observing the effects of physical activity intervention and highlighting the importance of physical activity in both states.; Conclusions and Relevance: To strengthen the evidence for the benefits of physical activity programs in women and to observe the effects depending on their menopausal state, there is an ongoing need for more rigorous randomized controlled trials of appropriate length and dose, with individualized exercise intensity.; Competing Interests: Financial disclosures/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Rulanda Marina, C., et al. (2023). "Patient-initiated follow-up in women with early-stage endometrial cancer: A long-term follow-up of the OPAL trial." BJOG : an international journal of obstetrics and gynaecology 130(13): 1593-1601.
	Objective: A long-term follow-up of the OPAL trial to compare the effect of patient-initiated (PIFU) versus hospital-based (HBFU) follow-up on fear of cancer recurrence (FCR), quality of life (QoL) and healthcare use after 34 months of follow-up.; Design: Pragmatic, multicentre randomised trial.; Setting: Four Danish departments of gynaecology between May 2013 and May 2016.; Population: 212 women diagnosed with stage I low-intermediate risk endometrial carcinoma.; Methods: The control group attended HBFU with regular outpatient visits (i.e., 8) for 3 years after primary treatment. The intervention group underwent PIFU with no prescheduled visits but with instructions about alarm symptoms and options of self-referral.; Main Outcome Measures: The endpoints were FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) and QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire C-30 (EORTC QLQ C-30), and healthcare use as measured by questionnaires and chart reviews after 34 months of follow-up.; Results: FCR decreased from baseline to 34 months in both groups and no difference was found between allocations (difference -6.31 [95% confidence interval -14.24 to 1.63]). QoL remained stable with no difference in any domains between the two arms at 34 months using a linear mixed model analysis. The use of healthcare was significantly lower in the PIFU group (P < 0.01).; Conclusion: Patient-initiated follow-up is a valid alternative to hospital-based follow-up for people who have been treated for endometrial cancer and have low risk of recurrence. (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Rumbidzai, M. and S. Prasanna (2021). "Fertility and recurrence outcomes for borderline ovarian tumour patients who undergo fertility sparing surgery."
	
Rumyantsev, A., et al. (2020). "Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes." Ann. Oncol. 31: S625-S626.
	
Runa, A., et al. (2019). "The efficacy and safety of traditional Chinese herbal medicine Kuntai in treatment of premature ovarian insufficiency: A meta-analysis." Chinese Journal of Evidence-Based Medicine 19(8): 953-959.
	Objectives To systematically review the efficacy and safety of traditional Chinese herbal medicine Kuntai in the treatment of premature ovarian insufficiency (POI). Methods PubMed, EMbase, The Cochrane Library, CBM, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on Kuntai for treating premature ovarian insufficiency from inception to August, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results Twenty-one RCTs involving 1 777 patients were included, which were categorized as Kuntai vs. western medicine and Kuntai combined with western medicine vs. western medicine. The results of meta-analysis showed that: the efficacy of Kuntai was equivalent to western medicine; effective rate (RR=2.78, 95%CI 1.73 to 4.45, P<0.000 01), the change of Kupperman's score (MD=-3.25, 95%CI -3.75 to -2.76, P<0.000 01), the change of serum FSH (MD=-6.99, 95%CI -8.07 to -5.90, P<0.000 01), E2 (MD=7.01, 95%CI 3.01 to 11.01, P=0.000 6) and LH (MD=-4.66, 95%CI -6.45 to -2.86, P<0.000 01) in Kuntai combined with hormone replacement therapy (HRT) group were higher than that in the HRT group. Conclusions Kuntai combined with HRT is superior to HRT alone in the effective rate, the change of Kupperman's score, the change of serum FSH, E2 and LH for patients with premature ovarian insufficiency. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusion.Copyright © 2019 West China University of Medical Science. All rights reserved.

Runxi, W., et al. (2022). "Efficacy and safety of Natural Products in the Treatment of Menopausal-like Syndrome Caused by Gynecologic Cancer Therapy : A Systematic Review and Meta-Analysis."
	
Ruseckaite, R., et al. (2021). "Outcomes collected in female pelvic floor surgical procedure registries and databases: a scoping review." International Urogynecology Journal 32(12): 3113-3130.
	Introduction and hypothesis: The objective was to overview the literature on the existing pelvic floor procedure registries and databases and to identify patient demographic, clinical and/or patient-reported data items for inclusion in the Australasian Pelvic Floor Procedure Registry (APFPR) Minimum Data Set (MDS). Method(s): We conducted a literature search on the MEDLINE, Embase, CINAHL and PsycINFO databases in addition to Google Scholar and grey literature to identify studies in the period January 2008 to January 2020. All were English studies of registries and databases on female adults undergoing surgery for pelvic floor disorders including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Studies were assessed on demographic and clinical patient characteristics, procedure or treatment type, health-related quality of life, adverse events and safety outcomes, captured by pelvic floor procedure registries or databases that have been established to date. Result(s): From 1662 studies, 29 publications describing 22 different pelvic floor registries and databases were included for analysis, 12 (55%) of which were multicentre. Six (27%) registries and databases involved solely SUI, eight (36%) were regarding POP, and the remaining eight (36%) focussed on both conditions. The majority of registries and databases captured similar details on patient characteristics, comorbidities and other clinical features, procedure or treatment type, health-related quality of life, adverse events, safety and efficacy. Conclusion(s): The findings of this scoping review will assist in determining the MDS for the APFPR, an initiative of the Australian government, to improve health and quality of life outcomes of women who undergo pelvic floor reconstructive procedures.Copyright © 2021, The International Urogynecological Association.

Russell, N., et al. (2019). "Effects of Yoga on Quality of Life and Pain in Women With Chronic Pelvic Pain: Systematic Review and Meta-Analysis." Journal of Women's Health Physical Therapy 43(3): 144-154.
	
Russo, E., et al. (2023). "Minimal Invasive Abdominal Sacral Colpopexy and Abdominal Lateral Suspension: A Prospective, Open-Label, Multicenter, Non-Inferiority Trial." Journal of Clinical Medicine 12(8): 2926.
	Background: Abdominal minimally invasive surgery has become increasingly prominent for the treatment of prolapse. Abdominal sacral colpopexy (ASC) is the gold standard for the treatment of advanced apical prolapse; however, alternative surgical approaches such as the abdominal lateral suspension (ALS) have been developed to improve patient outcomes. This study aims to determine whether ALS improves outcomes compared to ASC in multicompartmental prolapse patients. Method(s): A prospective, open-label, multicenter, non-inferiority trial was conducted in 360 patients who underwent ASC or ALS for the treatment of apical prolapse. The primary outcome was anatomical and symptomatic cure of the apical compartment at 1-year follow-up; secondary outcomes included prolapse recurrence, re-operation rate, and post-operative complications. A 300-patient cohort was subdivided into 200-patients who underwent ALS and 100-patients who underwent ASC. The confidence interval method was used to calculate the p-value of non-inferiority. Result(s): At the 12-months follow-up, the objective cure rate of the apical defect was 92% for ALS and 94% for ASC (recurrence rates were 8% and 6%, respectively, and the p-value for non-inferiority was <0.01). The mMesh complication rates were 1% and 2% for ALS and ASC, respectively. Conclusion(s): This study demonstrated that the ALS technique is not inferior to the gold standard ASC for the surgical treatment of apical prolapse.Copyright © 2023 by the authors.

Rustia, G. M., et al. (2022). "Short-Term Urinary Retention after Tension-Free Vaginal Tape Midurethral Sling Performed Alone or as a Concomitant Procedure." Female Pelvic Medicine and Reconstructive Surgery 28(3): E44-E48.
	Objective The objective was to determine whether a difference exists in short-term urinary retention after tension-free vaginal tape (TVT) midurethral sling placement when performed alone compared with when placed during a concomitant prolapse procedure. Methods We conducted a single-center retrospective cohort study that compared TVT procedures performed alone (group 1) to those with a concomitant prolapse procedure (group 2). The primary outcome was the proportion of patients discharged with an indwelling Foley catheter after failing postoperative voiding trial. Results There were 100 women in group 1 and 267 women in group 2. Concomitant prolapse procedures included vaginal approach (n = 47), robotic (n = 218), or both (n = 2). Forty-nine patients (13.4%) failed the initial voiding trial and 21 patients (5.7%) were discharged with an indwelling Foley catheter. The rate of short-term urinary retention requiring an indwelling catheter at discharge was not significantly different between group 1 and group 2 (9 [9.0%] vs 12 [4.5%], P = 0.1). The duration of catheterization after discharge was shorter in group 1 compared with group 2 (2.1 +/- 1.1 vs 4.3 +/- 2.0 days, P = 0.008). In multivariate analysis, patients discharged with a catheter were more likely to have diabetes with an odds ratio of 3.1 (95th confidence interval, 1.2-8.1). Conclusions The proportion of patients discharged with an indwelling catheter did not significantly differ if TVT was performed alone or at the time of a concomitant prolapse procedure (9.0% vs 4.5%, P = 0.1).Copyright © American Urogynecologic Society. All rights reserved.

Rustia, G. M., et al. (2023). "Pain With Differing Insufflation Pressures During Robotic Sacrocolpopexy: A Randomized Controlled Trial." Obstetrics and Gynecology 142(1): 151‐159.
	OBJECTIVE: To evaluate whether decreasing insufflation pressure reduces postoperative pain and opioid use in women undergoing robotic‐assisted sacrocolpopexy. METHODS: In a single‐blinded randomized trial, women with pelvic organ prolapse underwent robotic‐assisted sacrocolpopexy at either 12 mm Hg (experimental) or 15 mm Hg (standard) insufflation pressure. The primary outcome was pain rating on a visual analog scale (VAS) on postoperative day 1 within 24 hours of surgery. Secondary outcomes included VAS pain rating at outpatient follow‐up, inpatient and outpatient use of opioids, operative time, and estimated blood loss. A margin of 15 mm was considered clinically different on the VAS, and at 80% power, a sample size of at least 64 participants was needed to show significance. RESULTS: From April 27, 2021, to May 17, 2022, 80 women were enrolled, with 41 in the experimental group and 39 in the standard group. All participants underwent surgery as planned and attended a 2‐week postoperative follow‐up. Participants in the experimental group had less pain on postoperative day 1 with median VAS of 17.0 mm (interquartile range 26.0) compared with 29.0 mm (interquartile range 32.0, P=.007) in the standard group. No differences were noted in the secondary outcomes of operative time, estimated blood loss, or length of stay. Participants in the experimental group were noted to use fewer opioids while an inpatient (P=.04) and outpatient (P=.02). In multivariable analyses, lower insufflation pressure and increasing age were negatively associated with postoperative VAS scores. CONCLUSION: Lowering insufflation pressure (12 mm Hg) during robotic‐assisted sacrocolpopexy safely reduced postoperative pain and opioid use compared with standard pressure (15 mm Hg). CLINICAL TRIAL REGISTRATION: ClinialTrials.gov, NCT04858438.

Rutkowska, A., et al. (2022). "Use of Virtual Reality-Based Therapy in Patients with Urinary Incontinence: A Systematic Review with Meta-Analysis." International Journal of Environmental Research and Public Health 19(10).
	It is estimated that over 400 million people worldwide experience some form of urinary incontinence (UI). Pelvic floor muscle training (PFMT) is commonly used in cases of urine loss. Game therapy (GT) has been suggested as a new conservative modality for UI treatments. GT represents a form of virtual reality (VR) that allows users to interact with elements of a simulated scenario. The purpose of this review was to assess the potential of using VR-based PFMT in the treatment of UI with a particular focus on the impact of this form of therapy on the patients' muscle function, symptoms of UI and quality of life (QoL). The following electronic databases were searched: PubMed, Embase, Cochrane Library, Scopus and Web of Science. Systematic review methods were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Electronic medical databases were searched from inception to 28 January 2021. From a total of 38 articles, 26 were analyzed after removing duplicates, then 22 records were excluded according to inclusion criteria and 4 were assessed as full texts. Finally, 2 randomized controlled trials (RCT) with 79 patients were included. For the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the meta-analysis showed a significant difference in favor of the control condition (MD = 2.22; 95% CI 0.42, 4.01; I2 = 0%). Despite the popularity of the use of VR in rehabilitation, we found a scarcity of literature evaluating the application of VR in the field of UI therapy. Only one study matched all of the criteria established. The effects of VR training improved PFM function and QoL; however, these changes were comparable to those of traditional PFMT. It is not possible to reach final conclusions from one study; thus, further development of VR interventions in the field of UI treatments are needed.

Ruxin, W. and H. Haixia (2022). "Efficacy of Atosiban for repeated embryo implantation failure: A systematic review and meta-analysis."
	
Ruye, W., et al. (2022). "The effects of dietary antioxidants on glucose and lipid metabolism in women with Polycystic Ovary Syndrome:A Meta-analysis."
	
Ryan, E. S., et al. (2021). "Cost-Effectiveness of Venous Thromboembolism Prophylaxis during Neoadjuvant Chemotherapy for Ovarian Cancer." JCO oncology practice 17(8): E1075-E1084.
	PURPOSE:Two recent clinical trials have demonstrated that direct oral anticoagulants (DOACs) are effective as venous thromboembolism (VTE) prophylaxis in patients with moderate-To-high risk ambulatory cancer initiating chemotherapy. Patients with advanced ovarian cancer receiving neoadjuvant chemotherapy are at particularly increased risk of VTE. We performed a cost-effectiveness analysis from a health system perspective to determine if DOACs are a feasible prophylactic strategy in this population. METHOD(S):A simple decision tree was created from a health system perspective, comparing two strategies: prophylactic DOAC taken for 18 weeks during chemotherapy versus no VTE prophylaxis. Rates of VTE (7.3% DOAC v 13.6% no treatment), major bleeding (2.6% v 1.3%), and clinically relevant nonmajor bleeding (4.6% v 3.3%) were modeled. Cost estimates were obtained from wholesale drug costs, published studies, and Medicare reimbursement data. Probabilistic, one-way, and two-way sensitivity analyses were performed. RESULT(S):In the base case model, DOAC prophylaxis is more costly and more effective than no therapy (incremental cost-effectiveness ratio = $256,218 in US dollars/quality-Adjusted life year). In one-way sensitivity analyses, reducing the DOAC cost by 32% or raising the baseline VTE rate above 18% renders this strategy potentially cost-effective with an incremental cost-effectiveness ratio below $150,000 in US dollars/quality-Adjusted life year. CONCLUSION(S):Further confirmation of the true baseline VTE rate among women initiating neoadjuvant chemotherapy for ovarian cancer will determine whether prophylactic dose DOAC is a value-based strategy. Less costly VTE prophylaxis options such as generic DOACs (once available) and aspirin also warrant investigation. Copyright © American Society of Clinical Oncology.

Ryan, O. K., et al. (2023). "Comparing minimally invasive surgical and open approaches to pelvic exenteration for locally advanced or recurrent pelvic malignancies - Systematic review and meta-analysis." European Journal of Surgical Oncology 49(8): 1362-1373.
	Introduction: Pelvic exenteration (PE) is a complex multivisceral surgical procedure indicated for locally advanced or recurrent pelvic malignancies. It poses significant technical challenges which account for the high risk of morbidity and mortality associated with the procedure. Developments in minimally invasive surgical (MIS) approaches and enhanced peri-operative care have facilitated improved long term outcomes. However, the optimum approach to PE remains controversial. Method(s): A systematic literature search was conducted in accordance with PRISMA guidelines to identify studies comparing MIS (robotic or laparoscopic) approaches for PE versus the open approach for patients with locally advanced or recurrent pelvic malignancies. The methodological quality of the included studies was assessed systematically and a meta-analysis was conducted. Result(s): 11 studies were identified, including 2009 patients, of whom 264 (13.1%) underwent MIS PE approaches. The MIS group displayed comparable R0 resections (Risk Ratio [RR] 1.02, 95% Confidence Interval [95% CI] 0.98, 1.07, p = 0.35)) and Lymph node yield (Weighted Mean Difference [WMD] 1.42, 95% CI -0.58, 3.43, p = 0.16), and although MIS had a trend towards improved towards improved survival and recurrence outcomes, this did not reach statistical significance. MIS was associated with prolonged operating times (WMD 67.93, 95% CI 4.43, 131.42, p < 0.00001) however, this correlated with less intra-operative blood loss, and a shorter length of post-operative stay (WMD -3.89, 955 CI -6.53, -1.25, p < 0.00001). Readmission rates were higher with MIS (RR 2.11, 95% CI 1.11, 4.02, p = 0.02), however, rates of pelvic abscess/sepsis were decreased (RR 0.45, 95% CI 0.21, 0.95, p = 0.04), and there was no difference in overall, major, or specific morbidity and mortality. Conclusion(s): MIS approaches are a safe and feasible option for PE, with no differences in survival or recurrence outcomes compared to the open approach. MIS also reduced the length of post-operative stay and decreased blood loss, offset by increased operating time.Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology

ryrpjs, R. B. R. (2021). "Cannabidiol use in women with endometriosis and chronic pelvic pain: evaluation in pain and quality of life." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: D02.455.849.090.100 D26.660 The evaluation will be with 30 patients, divided into two groups: one treated with Cannabidiol and another control receiving placebo, each one with 15 patients. The proposed medication will be HempFlex 3000, an oral medication. HempFlex 3000 is an oil derived from 100% natural Cannabis sativa, presented in drops, with a concentration of 1.4 mg / drop, 50 mg / ml, with THC of up to 0.3%. Each bottle contains 60ml, with approximately one bottle per month used for each patient. This medicine will be made available with a donation from the Company GreenCare Store Inc. The dosage is based on the patient's weight and will be in accordance with the guidance of the pharmaceutical industry. In the first week it will be 5mg / kg, in the second week 10mg / kg, in the third week 15mg / kg and from the fourth week 20mg / kg. The placebo will also be provided by the same company, with characteristics similar to the medication. The product to be offered will be different only in relation to the active ingredient of Cannabidiol to be studied. The other characteristics will be exactly the same. The evaluation of the patients will be done through the visual analogue pain scale (VAS) and the Quality of Life Questionnaire focused on endometriosis (EHP 30 ‐ Endometriosis Health Profile Questionnaire ‐ translated and validated for Portuguese). These will be applied at the beginning of the survey and then monthly until completing 3 months. Thus, it will be possible to evaluate the action of the medication and compare it with the placebo. CONDITION: C13.351.500.163 Endometriosis, pelvic pain PRIMARY OUTCOME: To evaluate the use of Cannabidiol, derived from Cannabis sativa, in response to pain and quality of life in patients with endometriosis. The success criteria will be considered according to the responses to the questionnaires, such as a greater than 50% decrease in pain on the visual analog scale (VAS) and the statistical variation found in the responses to the Quality of Life Questionnaire focused on endometriosis (EHP 30 ‐ Endometriosis Health Profile Questionnaire ‐ translated and validated into Portuguese). SECONDARY OUTCOME: Indirect efficacy will also be assessed through the reported use of rescue medications and even the need to hospital care via the first aid for medications, to be informed in a report completed by the patient during the study. INCLUSION CRITERIA: Patients diagnosed with endometriosis, with an suggestive image exam, who maintain pain (visual analogue scale more than 5) even in the course of drug treatment with hormonal contraceptives for at least 3 months before the inclusion of the study

Ryssdal, M., et al. (2023). "Immunomodulatory Effects of Metformin Treatment in Pregnant Women With PCOS." The Journal of Clinical Endocrinology and Metabolism 108(9): e743-e753.
	Context: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade systemic inflammation and increased risk of pregnancy complications. Metformin treatment reduces the risk of late miscarriage and preterm birth in pregnant women with PCOS. Whether the protective effect of metformin involves immunological changes has not been determined.; Objective: To investigate the effect of metformin on the maternal immunological status in women with PCOS.; Methods: A post-hoc analysis was performed of two randomized controlled trials, PregMet and PregMet2, including longitudinal maternal serum samples from 615 women with PCOS. Women were randomized to metformin or placebo from first trimester to delivery. Twenty-two cytokines and C-reactive protein were measured in serum sampled at gestational weeks 5 to 12, 19, 32, and 36.; Results: Metformin treatment was associated with higher serum levels of several multifunctional cytokines throughout pregnancy, with the strongest effect on eotaxin (P < .001), interleukin-17 (P = .03), and basic fibroblast growth factor (P = .04). Assessment of the combined cytokine development confirmed the impact of metformin on half of the 22 cytokines. The immunomodulating effect of metformin was more potent in normal weight and overweight women than in obese women. Moreover, normoandrogenic women had the strongest effect of metformin in early pregnancy, whereas hyperandrogenic women presented increasing effect throughout pregnancy.; Conclusion: It appears that metformin has immunomodulating rather than anti-inflammatory properties in pregnancy. Its effect on the serum levels of many multifunctional cytokines demonstrates robust, persisting, and body mass-dependent immune mobilization in pregnant women with PCOS. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

s r l, L. L. P. (2022). Vitamin D, Epigallocatechin Gallate, D-chiro-inositol and Vitamin B6 in Uterine Fibroid.
	No Results Available Dietary Supplement: Epigallocatechin gallate, Vitamin D, Vitamin B6, D-chiro-inositol|Dietary Supplement: Placebo Diameter|Volume|Need for surgery|pVEGF-R|Marker of cellular proliferation Female Phase 3 60 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment DELPHYS PLUS August 1, 2023

S, S. P., et al. (2022). "Bioequivalence of a hybrid pegylated liposomal doxorubicin hydrochloride injection and Caelyx®: A single-dose, randomized, multicenter, open-label, two-period crossover study in patients with advanced ovarian cancer." European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 176: 106248.
	Objective: To evaluate the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyx®.; Methods: This multicenter, open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, bioequivalence study was conducted in female patients aged ≥18 years and ≤75 years with ovarian cancer, whose disease progressed or recurred after platinum-based chemotherapy, and who were scheduled to start PLD therapy. Patients were intravenously infused drugs over 1 h at 50 mg/m 2 dose two hours after breakfast on the first day of the chemotherapy cycle in period-I and crossed over to the other arm in period-II (day 29). Pharmacokinetic (PK) analyses were performed using two separate, validated liquid chromatography-mass spectrometry methods for encapsulated and unencapsulated doxorubicin.; Results: Both the test and reference formulations were well-tolerated and safe. The pharmacokinetic analysis for both encapsulated and unencapsulated doxorubicin was conducted in 50 patients and PK parameters were found to be comparable between test and reference products. The geometric mean ratios (90% confidence interval) of hybrid PLD/Caelyx® were; maximum measured plasma concentration (C max ): 91.94-97.28%, area under the plasma concentration versus time from time 0 to t (AUC 0-t ): 95.19-103.67% , AUC from time 0 to ∞ (AUC 0-∞ ): 95.13-103.66% for encapsulated doxorubicin and for unencapsulated doxorubicin C max : 92.08-116.46% , AUC 0-t : 91.91-108.28% , AUC 0-∞ : 93.45-110.05%.; Conclusion: The PLD formulation was found to be bioequivalent to Caelyx®. (Copyright © 2022. Published by Elsevier B.V.)

Saab, W., et al. (2021). "A systemic review of intravenous immunoglobulin G treatment in women with recurrent implantation failures and recurrent pregnancy losses." American journal of reproductive immunology (New York, N.Y. : 1989) 85(4): e13395.
	Over the last few decades, the advancement in reproductive technologies and protocols to improve embryo quality through culture techniques and genetic testing to eliminate chromosomally abnormal embryos resulted in better pregnancy rates and outcomes after fertility treatments. Unfortunately, some patients still struggle with recurrent implantation failures (RIFs) and recurrent pregnancy losses (RPLs). Immune etiologies have been attributed to play an important role in some of those patients. Maintaining a pre-conceptional anti-inflammatory environment for implantation and pregnancy continuation yields superior results. Intravenous immunoglobulin G (IVIG) treatment has been reported to enhance reproductive outcome in patients with RIF and RPL with immune dysregulations. In this systemic review, we analyzed outcomes of IVIG trials for RIF and RPL, its mechanism of action, dosing, administration, side-effects, and evidence for its use in women with RIF and RPL. (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Saad, A., et al. (2021). "Mobile interventions targeting common mental disorders among pregnant and postpartum women: An equity-focused systematic review." PloS One 16(10): e0259474.
	Introduction: Pregnant and postpartum women face major psychological stressors that put them at higher risk of developing common mental disorders, such as depression and anxiety. Yet, their limited access to and uptake of traditional mental health care is inequitable, especially during the COVID-19 pandemic. Mobile interventions emerged as a potential solution to this discontinued healthcare access, but more knowledge is needed about their effectiveness and impact on health equity. This equity-focused systematic review examined the effectiveness and equity impact of mobile interventions targeting common mental disorders among pregnant and postpartum women.; Methods and Results: We systematically searched MEDLINE, EMBASE, PsychINFO and 3 other databases, from date of database inception and until January 2021, for experimental studies on mobile interventions targeting pregnant and postpartum women. We used pooled and narrative synthesis methods to analyze effectiveness and equity data, critically appraised the methodological rigour of included studies using Cochrane tools, and assessed the certainty of evidence using the GRADE approach. Our search identified 6148 records, of which 18 randomized and non-randomized controlled trials were included. Mobile interventions had a clinically important impact on reducing the occurrence of depression (OR = 0.51 [95% CI 0.41 to 0.64]; absolute risk reduction RD: 7.14% [95% CI 4.92 to 9.36]; p<0.001) and preventing its severity perinatally (MD = -3.07; 95% CI -4.68 to -1.46; p<0.001). Mobile cognitive behavioural therapy (CBT) was effective in managing postpartum depression (MD = -6.87; 95% CI -7.92 to -5.82; p<0.001), whereas other support-based interventions had no added benefit. Results on anxiety outcomes and utilization of care were limited. Our equity-focused analyses showed that ethnicity, age, education, and being primiparous were characteristics of influence to the effectiveness of mobile interventions.; Conclusion: As the COVID-19 pandemic has increased the need for virtual mental health care, mobile interventions show promise in preventing and managing common mental disorders among pregnant and postpartum women. Such interventions carry the potential to address health inequity but more rigorous research that examines patients' intersecting social identities is needed.; Competing Interests: The authors have declared that no competing interests exist.

Sabatier, R., et al. (2023). "Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial." European journal of cancer (Oxford, England : 1990) 181: 42-52.
	Background: The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer. We evaluated maintenance olaparib plus bevacizumab in older patients in PAOLA-1.; Methods: Baseline clinical and molecular data, and PFS, were compared between older (aged ≥65 years) and younger patients (<65 years). Factors associated with olaparib efficacy, and safety in age subgroups, were also assessed.; Results: Of 806 randomised patients, 292 (36.2%) were ≥65 years. A lower proportion of older versus younger patients had an Eastern Cooperative Oncology Group performance status of 0 (61.0% versus 76.2%) and upfront surgery (42.0% versus 55.7%). Older patients were less likely to have a BRCA1/2 mutation (17.1% versus 36.7%) or homologous recombination deficiency-positive status (34.1% versus 55.7%). After median follow-up of 22.1 months, median PFS was 21.6 months with olaparib versus 16.6 months with placebo in the older population (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.41-0.75), comparable with the younger population (median 22.9 versus 16.9 months; HR 0.61, 95% CI 0.49-0.77). PFS benefits were observed in patients with a BRCA mutation or homologous recombination deficiency-positive tumours. Incidence of olaparib-related grade ≥3 adverse events in older patients was comparable with that of younger patients (36.8% versus 31.7%) although hypertension and anaemia were more common in older patients. No treatment-related deaths occurred in older patients receiving olaparib.; Conclusion: Older patients enrolled in PAOLA-1 achieved similar PFS benefits compared with younger patients, with a similar safety profile. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sabatino, J., et al. (2020). "Direct Oral Anticoagulants in Patients With Active Cancer: A Systematic Review and Meta-Analysis." JACC: CardioOncology 2(3): 428-440.
	Background: Many patients with cancer have a hypercoagulable state and an increased risk of developing venous thromboembolism (VTE), arterial occlusion, and pulmonary emboli. Patients with cancer may also have an increased risk of bleeding with anticoagulant treatment. Recent trials have reported that direct oral anticoagulants (DOACs) are noninferior to the low-molecular-weight heparin, dalteparin, in preventing VTE, but have a higher bleeding rate. Objective(s): This study compared the efficacy and risks of DOACs versus dalteparin in patients with cancer-related VTEs across all randomized controlled trials (RCTs). Method(s): This study performed a systematic analysis of RCTs published in PubMed, SCOPUS, and Google Scholar from September 1, 2007 through March 31, 2020 that reported clinical outcomes of treatment with DOACs versus dalteparin in patients with cancer with acute VTE. Two investigators independently performed study selection and data extraction. Extracted data were recorded and exported to statistical software for all analyses (OpenMetaAnalyst). Result(s): This study included 4 randomized trials (N = 2,907). Compared with DOACs, dalteparin was associated with higher VTE recurrence (risk ratio [RR]: 1.55; 95% confidence interval [CI]: 1.19 to 2.03; p = 0.001), whereas clinically relevant nonmajor bleeding (CRNMB) was significantly less frequent with dalteparin than that with DOACs (RR: 0.68; 95% CI: 0.54 to 0.86; p = 0.001). The risk of CRNMB was largely observed with patients with gastrointestinal malignancies. No significant differences were observed in major bleeding (RR: 0.74; 95% CI: 0.52 to 1.06; p = 0.11). Conclusion(s): DOACs were noninferior to dalteparin in preventing VTE recurrence in patients with cancer without a significantly increased risk of major bleeding. However, DOACs were associated with higher rates of CRNMB compared with dalteparin, primarily in patients with gastrointestinal malignancies.Copyright © 2020 The Authors

Sabbadin, C., et al. (2022). "Role of Renin-Angiotensin-Aldosterone System and Cortisol in Endometriosis: A Preliminary Report." International Journal of Molecular Sciences 24(1).
	Endometriosis is a chronic inflammatory disease associated with pelvic pain, infertility, and increased cardiovascular risk. Recent studies suggest a possible role of aldosterone as a pro-inflammatory hormone in the pathogenesis of the disease. Cortisol is also an important mediator of stress reaction, but its role is controversial in endometriosis. The aim of this study was to evaluate aldosterone and cortisol levels and blood pressure values in women with endometriosis. We measured blood pressure, plasma aldosterone, renin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) in 20 women with untreated minimal or mild pelvic endometriosis compared with 20 healthy controls matched for age and body mass index. Aldosterone values were similar in the two groups, while renin was significantly lower and the aldosterone to renin ratio was significantly higher in patients with endometriosis than in controls. Systolic blood pressure was in the normal range, but significantly higher in patients with endometriosis. Morning plasma cortisol was normal, but significantly lower in patients with endometriosis compared with controls, while DHEAS to cortisol ratio was similar in the two groups. These preliminary results are evidence of increased biological aldosterone activity and dysregulation of the hypothalamic-pituitary-adrenal axis in early stages of endometriosis. These alterations could play a role in disease development, suggesting new therapeutic targets for aldosterone receptor blockers.

Sabourin-Guardo, E., et al. (2020). "Premenstrual dysphoric disorder: Mental disorder or adjustment difficulty?" Annales Medico-Psychologiques 178(3): 283-289.
	Premenstrual dysphoric disorder (PMDD) is characterized by thymic (irritability, depressed mood, anxiety), physical (breast swelling, muscle pain), and behavioural (decreased interest, lethargy) cyclical symptoms that appear approximately one week before menstruation and begin to decrease after the luteal phase. Diagnosis considers the degree to which these symptoms have altered social or professional functioning during the year preceding consultation. DSM-III (Diagnostic and Statistical Manual of Mental Disorders) and DSM-IV working groups have successively decided not to attribute an official disorder status to PMDD, apprehending its possible negative impact (e.g., potential increase in prejudice against women through pathologization of natural female functioning and a risk of misuse). Since its inclusion in the DSM-5 (the latest edition of the American Psychiatric Association's DSM) in 2013, it has achieved official status of mental disorder. It is also expected to be included in the 11th revision of the International Classification of Diseases (ICD-11) according to the beta draft of the World Health Organisation. The current paper challenges the validity and relevance of PMDD inclusion in diagnostic textbooks through an argument from both sides on this issue. Criticism about PMDD largely comes from feminist groups, worried about the implications of including the diagnosis and its associated treatments, which are firmly rooted within the medical paradigm. The scientific community, however, is divided, and while some welcome the DSM-5 work group initiative, others are less enthusiastic. The DSM-5 work group identified sufficient empirical support to justify inclusion of PMDD in the Depressive disorders category. Their decision was based on an examination of the four requirements necessary for including any disorder in diagnostic textbooks, that is: (a) a clear distinction of PMDD from other disorders, (b) the presence of antecedent validators (environment and cultural consideration), (c) concomitant factors (biomarkers) and (d) predictive validator (PDMM's stability over time and drug treatment response). The current paper reviews these requirements. A first consideration leading to the inclusion of PMDD in DSM-5 is that it could clearly be distinguished from other mood disorders by the concordance between the premenstrual phase and the symptoms' onset. Indeed, the symptoms begin at the luteal phase and tend to disappear when menstruation ends. However, a meta-analysis reveals some issues in how symptoms ratings have been used in PMDD's studies. Furthermore, it appears that PMDD present high comorbidity with other disorders. A majority (73%) of PMDD cases are combined with another mental disorder (anxiety disorder, mood disorder, etc.). Secondly, PMDD work group advocates the importance of heritability, compared to what they describe as a very modest impact of environmental issues on symptoms' onset. That said, some studies highlight the association between PMDD and various life events and suggest that PMDD is a culture-bound phenomenon. Women who met PMDD criteria would have had experienced significantly more physical and sexual abuse, interpersonal problems, and mistreatment at work than women who did not meet the diagnostic criteria. In addition, women in Western Europe and North America appear to be at greater risk of having PMDD. Third, although no biological markers have systematically been associated with PMDD, notable differences on some gene of women with PMDD have recently been identified. However, biological markers that are characteristic of women with PMDD could be the result of traumatic antecedents rather than the unique cause of this psychological distress. Finally, the work group claims that some predictive factors, which predict the PMDD symptoms' and response to drug therapy, tend to confirm its existence. The fact that symptoms reappear at each cycle would demonstrate the disorder's periodicity and stability. Furthermore, the effectiveness of medications (Selective Serotonin Reuptake Inhibitor - SSRI) in treating this disorder has been a significant factor in the decision of its inclusion in the DSM-5. Nevertheless, the central role played by treatment response in PDMM validation has been challenged by some researchers. Scientific literature review urges to be careful regarding PMDD's place in the diagnostic textbook. Indeed, additional studies concerning discrimination of PMDD from other disorders, life event's role, intercultural issues, and biological correlates are warranted to confirm its validity. To conclude, the arguments raised in the current paper are not intended to invalidate the existence of women's premenstrual symptoms or emotional distress that some women may experience, but rather to debate on the legitimacy of PMDD's inclusion as a "disorder" in psychiatric textbooks and diagnostic manuals.Copyright © 2019 Elsevier Masson SAS

Saccone, G., et al. (2022). "Hysteroscopic resection vs dilation and evacuation for treatment of caesarean scar pregnancy: study protocol for a randomised controlled trial." Facts, views & vision in ObGyn 14(1): 83‐86.
	BACKGROUND: Caesarean scar pregnancy (CSP) is a type of ectopic pregnancy where the fertilised egg is implanted in the muscle or fibrous tissue of the scar after a previous caesarean section. Management options for women who opted for termination of CSP include sharp curettage, dilation and evacuation (D&E), excision of trophoblastic tissues, local or systemic administration of methotrexate, bilateral hypogastric artery ligation, and selective uterine artery embolisation with curettage and/or methotrexate administration. Recently hysteroscopic resection has also been proposed as an alternative option. OBJECTIVE: To compare the surgical outcome of hysteroscopic resection with dilation and evacuation (D&E) for the treatment of caesarean scar pregnancy (CSP). METHODS: Parallel‐group, non‐blinded, randomised clinical trial conducted at a single centre in Italy. Eligible women are those with singleton gestations at less than 9 weeks of gestation, and with thickness of myometrial layer =1 mm at the level of the ectopic. Inclusion criteria are women with CSP with positive embryonic/fetal heart activity who opted for termination of pregnancy. Patients will be randomised 1:1 to receive either hysteroscopic resection (i.e. intervention group) or D&E (i.e. control group). In both groups, 50 mg/m2 (based on DuBois formula for body surface area) of methotrexate (MTX) will be injected intramuscularly at the time of randomisation (day 1) and another dose at day 3. A third dose of MTX is planned in case of persistence of fetal heart activity on day 5. Participants will receive either D&E or hysteroscopic resection from 3 to 7 days after the last dose of MTX. A sample size of 54 women is planned. MAIN OUTCOME MEASURES: The primary outcome is the success rate of the treatment protocol, defined as no requirement for further treatment until complete resolution of the CSP as demonstrated by negative beta hCG levels and absence of residual gestational material on ultrasound examination.. STUDY HYPOTHESIS: Hysteroscopic surgery is superior to D&E for the treatment of CSP. WHAT IS NEW?: The results of the trial will provide information on the best treatment for CSP.

Sachdeva, S. and T. K. Rabbani (2021). "Rucabarib: a new lease of life for ovarian cancer patients." Journal of cancer research and therapeutics 17(4): 1123‐1124.
	Background: Rucaparib is a drug with potential as maintenence monotherapy in ovarian cancers irrespective of genetic mutation. Methods: The results of the ARIEL 3 trial were analysed for the drug's prospects towards cure in ovarian and other pelvic malignancies. Results: Ovarian cancer patients with highly malignant tumors and relapses on platinum based chemotherapy exhibited statistically significant reductions in tumor size with maintenance Rucaparib therapy vis a vis placebo. Conclusion: Genetic heterogeneity of the tumor did not have an impact upon Rucaparib efficacy in ovarian carcinoma. More malignant and relapsed variants can effectively be treated with Rucaparib, thereby improving survival rates and quality of life.

Sacristan-Martin, O., et al. (2019). "A mindfulness and compassion-based program applied to pregnant women and their partners to decrease depression symptoms during pregnancy and postpartum: study protocol for a randomized controlled trial." Trials 20(1): 654.
	Background: Pregnancy and the postpartum period are times of great change for women and their partners, often bringing substantial challenges and stress. Approximately 10%-20% of women suffer from mood disorders such as depression in the perinatal period. There are risks involved in using psychopharmacological interventions to treat perinatal depression. Mindfulness and compassion-based educational programs could be efficacious and cost-effective options for the prevention and treatment of perinatal mood disorders. The aim of this study is to assess the efficacy of an adapted Mindfulness-Based Childbirth and Parenting (MBCP) program that includes compassion training for pregnant women in primary care (PC) settings in the Spanish National Health System to decrease perinatal depression.; Methods: A multicenter randomized controlled trial (RCT) will be conducted. Participants will be pregnant women (n = 122) and their partners who wish to participate. They will be enrolled and assessed in PC settings and randomly assigned to either: (1) an adapted MBCP educational program tailored to the Spanish National Health System + treatment as usual (TAU); or (2) TAU only. The main outcome to be assessed will be depression, evaluated with the Edinburgh Postnatal Depression Scale (EPDS). Secondary outcomes will include self-reported measures of perceived stress, affects, mindfulness, self-compassion, maternal self-efficacy, and use of health and social services. Patients will be assessed at four timepoints: baseline; post-treatment; and at three and six months after childbirth. Intention-to-treat and per-protocol analyses will be carried out using linear regression mixed models. Effect sizes will be estimated using Cohen's d.; Discussion: Perinatal depression is a significant health problem. An effective and low-cost childbirth education program that incorporates mindfulness and compassion practices may be a beneficial preventive complementary healthcare modality for expectant women and their partners. This study will be the first multicenter RCT in Spanish PC settings using adapted MBCP and compassion practices to reduce symptoms of depression during pregnancy and the postpartum period.; Trial Registration: ClinicalTrials.gov, NCT03247491. Registered on 31 July 2017.

Sadegh, M.-T., et al. (2023). "Comparative Efficacy of Different Antidiabetic Agents as an Add-on Medication to Metformin in Women with Polycystic Ovary Syndrome (PCOS): A Systematic Review."
	
Sadowski, C. A. and Y. N. Al Hamarneh (2022). "Community pharmacist intervention to address lower urinary tract symptoms in older adults: A randomized controlled trial." International Journal of Clinical Pharmacy 44(6): 1564.
	Background and Objective: Lower urinary tract symptoms (LUTS), including urinary incontinence, are common in older adults, yet often unrecognized. Although pharmacists have knowledge regarding the therapeutics of LUTS, there are no randomized controlled trials demonstrating impact of their interventions on LUTS. In the province of Alberta, Canada, pharmacists have one of the broadest scopes of practice, supporting assessment and prescribing activities. The purpose of this project was to determine the impact of pharmacist case finding and intervention on LUTS in older adults. Method(s): The community pharmacies were identified through a pharmacy practice research network with EPICORE Centre, University of Alberta, and through email/social media invitations through the provincial pharmacy advocacy body. Pharmacists received a review of therapeutics regarding LUTS and were oriented to the study procedures and data entry. Patients were included if they were 60y and older, able to speak English, have an email address, and screen positive for LUTS symptoms. Once enrolled the patients were randomly assigned to a control arm where they completed a baseline questionnaire, and another a follow-up questionnaire at 8 weeks or an intervention arm where they completed a longer baseline questionnaire, met with the pharmacist for assessment and development of a care plan, and then completed another follow-up questionnaire at 8 weeks. Main Outcome Measure(s): For the patient bladder symptoms 3 validated tools are used, the Patient Perception of bladder Condition (PPBC), the Bladder Self-Assessment Questionnaire (B-SAQ), and the International Continence Questionnaire-Short Form (ICI-Q-SF), were measured at baseline and again at follow-up. The primary outcome was the PPBC. Secondary outcomes include pharmacist feasibility through time spent. Actions taken through the care plans are being captured. Result(s): The study was delayed due to COVID, and has been adapted to allow for online delivery. To date 15 patients were enrolled from 9 pharmacies (16 active pharmacists) across Alberta. Conclusion(s): Community pharmacist engagement for assessment and management of LUTS in older adults is feasible.

Sadullayev, A. and M. Medvediev (2022). "Comparison of the Effect on the Ovarian Reserve of Modern Methods of Treatment of Endometrioid Cysts." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 44(8): 908-914.
	Objective: To compare the efficacy and safety of autologous platelet-rich plasma (PRP) therapy in laparoscopy and transvaginal sclerotherapy for the treatment of endometrioid cysts for maintaining ovarian reserve.; Methods: The study included 71 women under age 35 years with primary and secondary infertility. Twenty women underwent sclerotherapy of endometrioid cysts followed by autologous PRP injection into ovarian tissue, and 21 underwent laparoscopic cyst removal by stripping followed by autologous PRP injection. The control group consisted of 30 women who underwent laparoscopic cystectomy by stripping without autologous PRP injection. We assessed ovarian reserve for all patients before surgery as well 3 and 6 months after surgery by measuring serum anti-Müllerian hormone (AMH) levels and calculating antral follicle count using ultrasound.; Results: In the control group, AMH levels had decreased significantly at 3 and 6 months post-surgery, whereas levels in laparoscopy and PRP group remained almost unchanged from initial levels. In the sclerotherapy group, we observed a tendency towards increased AMH levels, but it was not statistically significant when compared with initial results. Follicle count changes were similar to AMH patterns.; Conclusion: In this study, sclerotherapy in combination with PRP therapy for ovarian endometriomas was associated with improved measures of ovarian reserve, and the combination of laparoscopic excision of the endometrioma with PRP therapy facilitated ovarian reserve preservation. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Saeaib, N., et al. (2020). "Hormone replacement therapy after surgery for epithelial ovarian cancer." The Cochrane Database of Systematic Reviews 1: CD012559.
	Background: Women who have undergone surgical treatment for epithelial ovarian cancer (EOC) may develop menopausal symptoms due to immediate loss of ovarian function following surgery and chemotherapy. Women may experience vasomotor symptoms, sleep disturbance, difficulty concentrating, sexual dysfunction, vaginal symptoms and accelerated osteoporosis. Although hormone replacement therapy (HRT) is the most effective treatment to relieve these symptoms, its safety has been questioned for women with EOC.; Objectives: To assess the safety and efficacy of HRT for menopausal symptoms in women surgically treated for EOC.; Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 6), MEDLINE via Ovid (1946 to 12 June 2019) and Embase via Ovid (1980 to 2019, week 23). We also handsearched conference reports and trial registries. There was no language restriction.; Selection Criteria: We included randomized controlled trials (RCTs) with participants of any age and menopausal status who had undergone surgery for EOC and, after diagnosis and treatment, used any regimen and duration of HRT compared with placebo or no hormone therapy. We also included trials comparing different regimens or duration of administration of HRT.; Data Collection and Analysis: Two review authors independently identified studies that met the inclusion criteria. They used Covidence to extract study characteristics, outcome data and to assess methodological quality of the included studies.; Main Results: Our search strategy identified 2617 titles, of which 2614 titles were excluded. Three studies, involving 350 women, met our inclusion criteria. Two of the studies included pre and postmenopausal women, and the third only included premenopausal women. The overall age range of those women included in the studies was 20 to 89.6 years old, with a median follow-up ranging from 31.4 months to 19.1 years. The geographical distribution of participants included Europe, South Africa and China. All stages and histological subtypes were included in two of the studies, but stage IV disease had been excluded in the third. The three included studies used a variety of HRT regimens (conjugated oestrogen with or without medroxyprogesterone and with or without nylestriol) and HRT administrations (oral, patch and implant), In all studies, the comparisons were made versus women who had not received HRT. The studies were at low or unclear risk of selection and reporting bias, and at high risk of performance, detection and attrition bias. The certainty of the evidence was low for overall survival and progression-free survival, and very low for quality-of-life assessment, incidence of breast cancer, transient ischaemic attack (TIA), cerebrovascular accident (CVA) and myocardial infarction (MI). Meta-analysis of these studies showed that HRT may improve overall survival (hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.54 to 0.93; 350 participants, 3 studies; low-certainty evidence). Quality-of-life assessment by use of the EORTC-C30 questionnaire was performed only in one study. We are uncertain whether HRT improves or reduces quality of life as the certainty of the evidence was assessed as very low (mean difference (MD) 13.67 points higher, 95% CI 9.26 higher to 18.08 higher; 1 study; 75 participants; very low-certainty evidence). Likewise, HRT may make little or no difference to progression-free survival (HR 0.76, 95% CI 0.57 to 1.01; 275 participants, 2 studies; low-certainty evidence). We are uncertain whether HRT improves or reduces the incidence of breast cancer (risk ratio (RR) 2.00, 95% CI 0.19 to 21.59; 225 participants, 2 studies; very low-certainty evidence); TIA (RR 5.00, 95% CI 0.24 to 102.42; 150 participants, 1 study; very low-certainty evidence); CVA (RR 0.67, 95% CI 0.11 to 3.88; 150 participants, 1 study; very low-certainty evidence); and MI (RR 0.20, 95% CI 0.01 to 4.10; 150 participants, 1 study; very low-certainty evidence). The incidence of gallstones was not reported in the included studies.; Authors' Conc usions: Hormone replacement therapy may slightly improve overall survival in women who have undergone surgical treatment for EOC, but the certainty of the evidence is low. HRT may make little or no difference to quality of life, incidence of breast cancer, TIA, CVA and MI as the certainty of the evidence has been assessed as very low. There may be little or no effect of HRT use on progression-free survival. The evidence in this review is limited by imprecision and incompleteness of reported relevant outcomes and therefore the results should be interpreted with caution. Future well-designed RCTs are required as this is an important area to women experiencing menopausal symptoms following surgical treatment for ovarian cancer, especially as doctors are often reluctant to prescribe HRT in this scenario. The evidence in this review is too limited to support or refute that HRT is very harmful in this population. (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Saerens, M., et al. (2021). "Risk of Thrombo-Embolic Events in Ovarian Cancer: Does Bevacizumab Tilt the Scale? A Systematic Review and Meta-Analysis." Cancers 13(18).
	Thromboembolic events are the second cause of death in cancer patients. In ovarian cancer, 3-10% of patients present with venous thromboembolism (VTE), but the incidence may rise to 36% along the disease course. Bevacizumab is a monoclonal antibody directed against vascular endothelial-derived growth factor, and in in vitro studies it showed a predisposition to hemostasis perturbation, including thrombosis. However, in vivo and clinical studies have shown conflicting results for its use as a treatment for ovarian cancer, so we conducted a systematic review and meta-analysis on the risk of arterial thromboembolism (ATE) and VTE in ovarian cancer patients treated with bevacizumab. The review comprised 14 trials with 6221 patients: ATE incidence was reported in 5 (4811 patients) where the absolute risk was 2.4% with bevacizumab vs. 1.1% without (RR 2.45; 95% CI 1.27-4.27, p = 0.008). VTE incidence was reported in 9 trials (5121 patients) where the absolute risk was 5.4% with bevacizumab vs. 3.7% without (RR 1.32; 95% CI 1.02-1.79, p = 0.04). Our analysis showed that the risk of arterial and venous thromboembolism increased in patients treated with bevacizumab. Thrombolic events (TEs) are probably underreported, and studies should discriminate between ATE and VTE. Bevacizumab can be considered as an additional risk factor when selecting patients for primary prophylaxis with anticoagulants.

Sahasikdar, S., et al. (2023). "Comparing Combined Pills to Progesterone-Only Pills for Abnormal Uterine Bleeding in Perimenopausal Women." International Journal of Pharmaceutical and Clinical Research 15(9): 1332-1345.
	Abnormal uterine bleeding (AUB) is a prevalent and troubling indication encountered by perimenopausal females, frequently requiring medical interference. This investigation seeks to evaluate the efficiency and security of merged oral contraceptive pills (COCs) and progesterone-only pills (POPs) in the handling of AUB in perimenopausal females. A randomised regulated experiment was carried out; involving 300 participants aged 45 to 55 years with abnormal uterine bleeding. Participants were arbitrarily allocated to receive either combined oral contraceptives or progestin-only pills for a period of 6 months. The main result measures were decrease in haemorrhage severity and enhancement in quality of existence, evaluated using standardised scales. Additional outcomes encompassed adverse reactions, uterine lining examination, and client contentment. Data examination unveiled that both Contraceptive Oral Contraceptives (COCs) and Persistent Organic Pollutants (POPs) were efficacious in diminishing haemorrhage severity and enhancing standard of living (p < 0.05). Nevertheless, combined oral contraceptives (COCs) were linked with a greater occurrence of adverse reactions in contrast to progestin-only pills (POPs) (p < 0.05). Endometrial histopathology revealed no noteworthy disparities between the two cohorts. Patient contentment was greater in the POPs group (p < 0.05). In summary, both COCs and POPs are feasible choices for handling AUB in perimenopausal women, with POPs providing a favourable side effect profile and increased patient contentment.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Sahasikdar, S., et al. (2023). "Comparing Combined Pills to Progesterone-Only Pills for Abnormal Uterine Bleeding in Perimenopausal Women."  15(9): 1332‐1345.
	Abnormal uterine bleeding (AUB) is a prevalent and troubling indication encountered by perimenopausal females, frequently requiring medical interference. This investigation seeks to evaluate the efficiency and security of merged oral contraceptive pills (COCs) and progesterone‐only pills (POPs) in the handling of AUB in perimenopausal females. A randomised regulated experiment was carried out; involving 300 participants aged 45 to 55 years with abnormal uterine bleeding. Participants were arbitrarily allocated to receive either combined oral contraceptives or progestin‐only pills for a period of 6 months. The main result measures were decrease in haemorrhage severity and enhancement in quality of existence, evaluated using standardised scales. Additional outcomes encompassed adverse reactions, uterine lining examination, and client contentment. Data examination unveiled that both Contraceptive Oral Contraceptives (COCs) and Persistent Organic Pollutants (POPs) were efficacious in diminishing haemorrhage severity and enhancing standard of living (p < 0.05). Nevertheless, combined oral contraceptives (COCs) were linked with a greater occurrence of adverse reactions in contrast to progestin‐only pills (POPs) (p < 0.05). Endometrial histopathology revealed no noteworthy disparities between the two cohorts. Patient contentment was greater in the POPs group (p < 0.05). In summary, both COCs and POPs are feasible choices for handling AUB in perimenopausal women, with POPs providing a favourable side effect profile and increased patient contentment.

Şahin Meryem, V. and o. Medicine Gulhane School (2022). The Effect of Music Therapy on Sleep Quality and Depression in Menopausal Women.
	No Results Available Other: music therapy Pittsburgh sleep quality index (PUKI)|Beck Depression Scale|Menopausal Symptoms Evaluation Scale Female Not Applicable 70 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care meryemvrlshn00000000001 November 1, 2022

Sahin, N., et al. (2022). "The effect of pelvic floor exercises performed with EMG biofeedback or a vaginal cone on incontinence severity, pelvic floor muscle strength, and quality of life in women with stress urinary incontinence: a randomized, 6-month follow-up study." International Urogynecology Journal 33(10): 2773-2779.
	Introduction and Hypothesis: The objective was to assess the effectiveness of pelvic floor exercises performed with electromyographic (EMG) biofeedback or a vaginal cone on incontinence severity, muscle strength, social activity level, quality of life, treatment success, and treatment satisfaction in women with stress urinary incontinence (SUI).; Methods: This prospective, randomized study included 40 female patients diagnosed with SUI. Patients were randomly divided into two groups as the group receiving pelvic floor muscle exercise (PFME) with a vaginal cone at home (n = 20) and the group receiving PFME with EMG biofeedback in the hospital (n = 20). The measurement of urinary incontinence severity with a 1-h pad test, assessment of social activity with the social activity index (SAI), assessment of incontinence-specific quality of life, manual measurement of pelvic floor muscle strength, and the assessment of treatment satisfaction were performed in the pre-treatment period and post-treatment at 3 and 6 months.; Results: In intragroup analyses, an improvement was observed in both groups in the pad test, muscle strength, SAI, quality of life, and treatment satisfaction measurement compared with the pre-treatment period (p < 0.05). No significant difference was found between the groups in terms of assessment parameters in intergroup analyses during follow-up (p > 0.05).; Conclusion: It was concluded that both EMG biofeedback assisted PFME and PFME with a vaginal cone had curative effects on incontinence in patients with SUI. We believe that both protocols can be used as acceptable and effective conservative therapy methods in the treatment of women with SUI considering their preference. (© 2021. The International Urogynecological Association.)

Sahraeian, S., et al. (2023). "Extracellular Vesicle-Derived Cord Blood Plasma and Photobiomodulation Therapy Down-Regulated Caspase 3, LC3 and Beclin 1 Markers in the PCOS Oocyte: An In Vitro Study." Journal of lasers in medical sciences 14: e23.
	Introduction: Polycystic ovary syndrome (PCOS) is the communal endocrine illness in women and the most common cause of infertility due to lack of ovulation. The exact cause of PCOS is still unknown. Affected women may have difficulty getting pregnant due to ovulation problems. Various methods have not been effective in the treatment of PCOS due to the positive role of photobiomodulation therapy (PBMT) and extracellular vesicles (ECV) obtained from cord blood plasma in the treatment of various diseases. The aim of this study was to study the role of ECV and PBMT in maturation and improvement of infertility in women with PCOS. Methods: In this research, a number of oocytes were obtained after ovarian stimulation from women who had been referred to the hospital for infertility treatment after obtaining personal consent, and they were divided into three groups: control, ECV and PBMT. Subsequently, in vitro maturation (IVM) was assessed, then some oocytes were cultured with a routine medium and others were treated with ECV and PBMT. Real-time PCR was used to evaluate BCL-2, BAX, caspase-3, and autophagy gene (ATG5, LC3, Beclin 1). Oocyte glutathione (GSH), oxidised gluathione (GSSG), and reactive oxygen species (ROS) were measured. Results: The metaphase II (MII) oocyte ratio formation significantly increased in the ECV and PBMT groups ( P <0.05). The expression of the BCL-2 gene was significantly up-regulated in the ECV and PBMT groups, but the expression of BAX and caspase-3 significantly decreased ( P <0.05). The expression of the ATG5, LC3, BECLIN-2 genes significantly decreased in the ECV and PBMT groups ( P <0.05). ROS, GSSG decreased in ECV and PBMT groups but GSH increased ( P <0.05). Conclusion: The use of ECV and PBMT can increase the rate of fertilization and maturation of an oocyte and cause a decrease in apoptosis, autophagy, and ROS in a PCOS oocyte.; Competing Interests: The authors declare that there is no conflict of interest. (Copyright © 2023 J Lasers Med Sci.)

Sahraian, K., et al. (2024). "Effectiveness of mindful self-compassion therapy on psychopathology symptoms, psychological distress and life expectancy in infertile women treated with in vitro fertilization: a two-arm double-blind parallel randomized controlled trial." BMC Psychiatry 24(1): 174.
	Objectives: Infertility is a prominent problem affecting millions of couples worldwide. Recently, there has been a hightened emphasis on elucidating the subtle linkages between infertility treatment leveraging assisted reproductive technology and the complex realm of psychological challenges, as well as efforts in implementation of psychological interventions.The Mindful Self-Compassion (MSC) program seeks to improve self-compassion, compassion for others, mindfulness, and life satisfaction while reducing depression, anxiety, and stress. In the current study, an MSC intervention was performed on infertile women (IW) undergoing in vitro fertilization (IVF) to assess the effectiveness of this intervention in reducing psychological distress and psychopathological symptoms and enhancing life expectancy.; Methods: Fifty-seven IW undergoing IVF were randomly allocated to two groups: MSC (n = 29) or treatment as usual (TAU; n = 28). Participants in MSC met once a week for two hours for eight weeks and attended a half-day meditation retreat. The Synder's Hope questionnaire and the Revised 90-Symptom Checklist (SCL-90-R) were used as the primary outcome measures. Data were obtained before the intervention, immediately after the intervention, and two months post-intervention. Repeated measures of ANCOVA and paired t-tests in all assessment points were used to compare the MSC and the TAU groups in outcomes.; Results: In the MSC group, hopelessness, anger-hostility, anxiety, interpersonal sensitivity difficulties, and depression were significantly reduced compared with the TAU group, and those improvements persisted at the two-month follow-up. Reliable change index revealed that the MSC group's gains were both clinically significant and durable.; Conclusions: MSC can facilitate higher life satisfaction and mental well-being for IW undergoing IVF by reducing psychological distress, psychopathological symptoms, and hopelessness. These encouraging findings call for more research into the effectiveness of mindfulness-based therapies in addressing psychological problems among IW undergoing IVF. (© 2024. The Author(s).)

Saibudeen, A., et al. (2019). "Pain Management Protocols During Uterine Fibroid Embolisation: A Systematic Review of the Evidence." Cardiovascular and interventional radiology 42(12): 1663-1677.
	Background: Uterine fibroid embolisation (UFE) is an effective treatment for fibroids. There are varying analgesia protocols published to control procedure associated pain. We aimed to assess what protocols are most effective in controlling post-procedural pain.; Materials and Methods: A systematic review of the Embase and Medline databases was conducted according to PRISMA guidelines. Studies regarding analgesia protocols post-uterine fibroid embolisation with Visual Analogue Scale or Numerical Rating Scale pain scores were included. The mean maximal pain scores of patients post-procedure were evaluated. ANOVA and t tests were performed.; Results: We identified 26 studies (total 3353 patients), with a mean procedural success rate of > 87%. We stratified protocols into four groups. Mean pain scores were: opioids ± NSAIDs ± acetaminophen (4.84, SD = 1.56); opioids ± NSAIDs ± acetaminophen + nerve block (4.7, SD = 1.37); opioids ± NSAIDs ± acetaminophen + intrauterine artery drug administration (4.09, SD = 0.60); and opioids ± NSAIDs ± acetaminophen + other (5.30, SD = 1.13) without significant difference between groups (p = 0.71). Similarly, there was no difference (p = 0.057) between groups for time to discharge or side effects.; Conclusions: There is no evidence to suggest that there is any superiority of one protocol above another in the published literature. Appropriate use of opioids ± NSAIDs ± acetaminophen alone appears to be sufficient to control pain post-UFE. However, due to large heterogeneity of the literature no firm conclusions can be reached, and further research is warranted.; Level of Evidence: Level 1, Systematic review.

SaiHua, Z. and C. XianQian (2023). "A systematic review and meta-analysis of antioxidant Vitamins Supplementation Reducing Endometriosis Related Pelvic Pain in Humans." PROSPERO International prospective register of systematic reviews.
	
Sairally Bibi Zeyah, F., et al. (2023). "Myoinositol or D-chiro-inositol for PCOS symptoms in adolescents: a narrative review." Journal of pediatric endocrinology & metabolism : JPEM 37(2): 91-101.
	Background: Polycystic ovary syndrome (PCOS) treatment in adolescents currently focuses on lifestyle interventions, with pharmacological treatment options often limited to hormonal contraceptives. Several of these carry broad side-effect profiles and are not always accepted by young girls. There is growing interest in non-hormonal therapies for PCOS. We aimed to collate the evidence on the use of myoinositol or D-chiro-inositol in the improvement of PCOS symptoms in symptomatic adolescents.; Content: A systematic literature review identifying key articles from inception to March 2023. Participants: Female adolescents (aged 12-19 years) with PCOS or PCOS-like features. Intervention: Myoinositol or D-chiro-inositol with or without additional interventions. Comparison: Any other treatment, including lifestyle interventions, hormonal therapy, metformin or no treatment. The main outcome measure were improvement in symptoms, quality of life and adverse effects.; Summary: Eight studies were included: two randomised open-label trials, one quasi-randomised and three non-randomised interventional studies, one case-control study and one cohort study. All studies showed improvements in some biochemical markers, metabolic parameters or clinical symptoms, but these were not reproducible across all studies.; Outlook: The benefit of myoinositol in adolescents with PCOS remains unclear, with limited high-quality evidence. This review highlights the need for robustly conducted research to inform clinical practice. (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Sajeev, A., et al. (2022). "Modulation of diverse oncogenic signaling pathways by oroxylin A: An important strategy for both cancer prevention and treatment." Phytomedicine : international journal of phytotherapy and phytopharmacology 105: 154369.
	Background: Regardless of major advances in diagnosis, prevention and treatment strategies, cancer is still a foreboding cause due to factors like chemoresistance, radioresistance, adverse side effects and cancer recurrence. Therefore, continuous development of unconventional approaches is a prerequisite to overcome foregoing glitches. Natural products have found their way into treatment of serious health conditions, including cancer since ancient times. The compound oroxylin A (OA) is one among those with enormous potential against different malignancies. It is a flavonoid obtained from the several plants such as Oroxylum indicum, Scutellaria baicalensis and S. lateriflora, Anchietea pyrifolia, and Aster himalaicus.; Purpose: The main purpose of this study is to comprehensively elucidate the anticancerous effects of OA against various malignancies and unravel their chemosensitization and radiosensitization potential. Pharmacokinetic and pharmacodynamic studies of OA have also been investigated.; Method: The literature on antineoplastic effects of OA was searched in PubMed and Scopus, including in vitro and in vivo studies and is summarized based on a systematic review protocol prepared according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The term "oroxylin A" was used in combination with "cancer" and all the title, abstracts and keywords appeared were considered.; Results: In Scopus, a total of 157 articles appeared out of which 103 articles that did not meet the eligibility criteria were eliminated and 54 were critically evaluated. In PubMed, from the 85 results obtained, 26 articles were eliminated and 59 were included in the preparation of this review. Mounting number of studies have illustrated the anticancer effects of OA, and its mechanism of action.; Conclusion: OA is a promising natural flavonoid possessing wide range of pleiotropic properties and is a potential anticancer agent. It has a great potential in the treatment of multiple cancers including brain, breast, cervical, colon, esophageal, gall bladder, gastric, hematological, liver, lung, oral, ovarian, pancreatic and skin. However, lack of pharmacokinetic studies, toxicity assessments, and dose standardization studies and adverse effects limit the optimization of this compound as a therapeutic agent. (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Sajjal, W., et al. (2021). "Progestin dominant impact consolidatedoral contraception on advancement of uterine fibroids." Pakistan journal of medical and health sciences 15(4): 1374‐1375.
	Background and objectives: Fibroids are the most well‐known tumors of the female pelvis. The tumors are considerate and happen in roughly 30% to half of ladies more than 35 years of age, and all the more habitually in individuals of color. The main objective of this study was to analyse the progestin dominant impact consolidatedoral contraception on advancement of uterine fibroids. Material and methods: This randomized controlled trial was conducted at Women Christian Hospital Multan during from July 2019 to July 2020. The data was collected from 50 patients who were suffering from uterine fibroids and they all treated with combined oral contraception. Results: The data was collected from 50 patients. 20 patients were considered in control group for comparison with study group. The patients treated with COC didn't have any clinical issues. In 13 patients (13.4%) under monophasic joined pills, the development of fibroids just as issues like menorrhagia, pallor, stomach agony and dysmenorrhea proceeded or expanded. Fundamental issue in 10 patients was serious uterine dying (surmised blood loss of 300ml), 3 experienced stomach and pelvic pain. Conclusion: It is concluded that uterine fibroids are very common. Numerous ladies need no mediation for their fibroids. Numerous ladies just need traditionalist treatment.

Sakaguchi-Mukaida, H., et al. (2023). "Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors." Cancers 15(18).
	Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates ( n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival ( n = 3; 87.0-100% versus 70.0-100%), disease-free survival ( n = 3; 87.0-100% versus 70.0-100%), recurrence rate ( n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.

Sakulpaisal, M., et al. (2023). "The effects of exogenous estrogen in women with SAR-CoV-2 infection: a systematic review and meta-analysis." Human reproduction (Oxford, England) 38(6): 1111-1123.
	STUDY QUESTION: Does exogenous estrogen use affect COVID-19-related mortality in women? SUMMARY ANSWER: Menopausal hormone therapy (MHT) was associated with a lower likelihood of all-cause fatality related to COVID-19 in postmenopausal women (odds ratio (OR) 0.28, 95% CI 0.18, 0.44; 4 studies, 21 517 women) but the combined oral contraceptive pill in premenopausal women did not have a significant effect (OR 1.00, 95% CI 0.42-2.41; 2 studies, 5099 women). WHAT IS KNOWN ALREADY: Men are much more likely to die from COVID-19 than women. STUDY DESIGN, SIZE, DURATION: In this systematic meta-analysis, a literature search was conducted using the following search terms related toCOVID-19 and estrogen, sex hormones, hormonal replacement, menopause, or contraception. The PubMed, Scopus, Cochrane Library, and EMBASE databases were searched to identify relevant studies published between December 2019 and December 2021. We also searched MedRxiv as a preprint database and reviewed the reference lists of all included studies and clinical trial registries for ongoing clinical studies until December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: All comparative studies that compared the rates mortality and morbidity (hospitalization, intensive care unit (ICU) admission, and ventilation support) due to COVID-19 in women using exogenous estrogen to a control group of women (nonusers) were included. A review of the studies for inclusion, extraction of data, and assessment of the risk of bias was performed independently by two reviewers. The ROBINS-I tool and the RoB 2 tool were used for bias assessment of the included studies. Pooled odds ratios (ORs) with 95% CIs were calculated using Review Manager V5.4.1. The I2 statistic was used to quantify heterogeneity. The quality of the evidence was assessed using GRADE criteria. MAIN RESULTS AND THE ROLE OF CHANCE: After searching the databases, we identified a total of 5310 studies. After removing duplicate records, ineligible studies, and ongoing studies, a total of four cohort studies and one randomized controlled trial comprising 177 809 participants were included in this review. There was a moderate certainty of evidence that MHT was associated with a lower likelihood of all-cause fatality related to COVID-19 (OR 0.28, 95% CI 0.18, 0.44; I2 = 0%; 4 studies, 21 517 women). The review indicated a low certainty of evidence for other outcomes. The mortality rate of premenopausal women in the combined oral contraceptive pill group did not differ significantly from the control group (OR 1.00, 95% CI 0.42-2.41; 2 studies, 5099 women). MHT marginally increased the rate of hospitalization and ICU admission (OR 1.37, 95% CI 1.18-1.61; 3 studies, 151 485 women), but there was no significant difference in the need for respiratory support between MHT users and nonusers (OR 0.91, 95% CI 0.52-1.59; 3 studies, 151 485 women). Overall, the tendency and magnitude of the effects of MHT in postmenopausal women with COVID-19 were consistent across the included studies. LIMITATIONS, REASONS FOR CAUTION: The certainty of the evidence for other outcomes of this review may be limited, as all included studies were cohort studies. In addition, the dosages and durations of exogenous estrogen used by postmenopausal women varied from study to study, and combined progestogen administration may have had some effect on the outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study can aid in counseling postmenopausal women taking MHT when they are diagnosed with COVID, as they have a lower chance of death than those not taking MHT. STUDY FUNDING/COMPETING INTEREST(S): Khon Kaen University provided financial support for this review and had no involvement at any stage of the study. The authors have no conflicts of interest to declare. REGISTRATION NUMBER: PROSPERO, CRD42021271882.

Salamanca University, o. (2021). Transcutaneous Tibial Nerve Stimulation as Treatment for Women With Primary Dysmenorrhea.
	No Results Available Procedure: Transcutaneous tibial nerve stimulation|Procedure: Placebo Changes in pain perception assessed using a 100 mm Visual Analogue Scale (VAS).|Changes in pain perception assessed using the Short-Form McGill Pain Questionnaire (SF-MPQ®).|Changes in the non-steroidal anti-inflammatory drugs (NSAID) intake using a NSAID diary designed for this study.|Changes in life quality assessed using the SF36 Health Survey (SF-36v2®).|Changes in sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI®).|To assess the overall improvement and satisfaction of the treatment using the Patient Global Impression of Change (PGIC®) questionnaire.|To assess the overall improvement and satisfaction of the treatment using a Likert Scale designed for this study.|To collect the possible adverse reactions caused by the treatment. Female Not Applicable 55 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment Tibial2021 April 30, 2022

Salamanna, F., et al. (2021). "Clinical Characteristics, Treatment Modalities, and Potential Contributing and Prognostic Factors in Patients with Bone Metastases from Gynecological Cancers: A Systematic Review." Diagnostics (Basel, Switzerland) 11(9).
	The purpose of this study is to review the clinical characteristics, treatment modalities, and potential contributing and prognostic factors of bone metastases from gynecological cancers (GCs). A systematic literature search on PubMed, Scopus, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases was conducted. Thirty-one studies, all retrospective, were included in this review, for a total of 2880 patients with GC bone metastases. Primary tumors leading to bone metastases included endometrial cancer (EC), cervical cancer (CC), ovarian cancer (OC), uterine sarcoma (US) and vulvar cancer (VuC), mainly with an International Federation of Gynecology and Obstetrics (FIGO) Stage of III and IV. The main bone metastatic lesion site was the vertebral column, followed by the pelvic bone and lower extremity bones. The median survival rate after bone metastases diagnosis ranged from 3.0 to 45 months. The most frequent treatments were palliative and included radiotherapy and chemotherapy, followed by surgery. The findings of this review give a first dataset for a greater understanding of GC bone metastases that could help clinicians move toward a more "personalized" and thus more effective patient management.

Salaminia, S., et al. (2019). "Hormone replacement therapy and postmenopausal cardiovascular events: A meta-analysis." Iranian Red Crescent Medical Journal 21(2): e82298.
	Context: Hormone replacement therapy (HRT) is widely used to control postmenopausal symptoms. This therapy is also used to prevent diseases such as osteoporosis and dementia. However, clinical trials suggest some negative effects regarding postmenopausal HRT. This study evaluates the effects of HRT on postmenopausal cardiovascular events. Evidence Acquisition: We collected data from 32 articles by using valid keywords and searching databases of PubMed, Medlib, ScienceDirect, EmBase, Scopus, Index Copernicus, SID, and Iranmedex. Analysis was performed by comparing three groups of postmenopausal women: combined hormone therapy (estrogen + progesterone), estrogen alone treated group, and placebo-receiving group (control group). Data were analyzed using the random effect model meta-analysis by using R software and Stata software Version 11.2. Result(s): Of the collected 32 studies between 1998 and 2016, there were 1277686 subjects with an average age of 60.6 years. The prevalence of myocardial infarction were (2.64%), coronary heart disease (1.7%), stroke (254%), cardiovascular death (1.54%), revascularization (3.26 %), and cerebrovascular disease (CVD) (2.78%) in the combined hormone therapy group. Also, in the estrogen-treated group were 2.95%, 3.41%, 2.49%, 2.8%,-, 3.14%, respectively. In the placebo-receiving group these events were 2.09%, 2.73%, 2.9%, 2.25%, 4.96%, and 11.92, respectively. The results showed that estrogen therapy could increase the incidence of stroke. Moreover, HRT could have positive effects on the serum lipid profile in postmenopausal women. Conclusion(s): Postmenopausal HRT appears to be non-effective on coronary artery disease, revascularization, myocardial infarction, and cardiac-related deaths; however, it could play a role in increasing the stroke rate.Copyright © 2019, Author(s).

Salarfard, M., et al. (2021). "The effect of herbal medicines on vaginal atrophy in postmenopausal women: A systematic review and meta-analysis." Iranian Journal of Obstetrics, Gynecology and Infertility 24(13): 100-118.
	Introduction: Vaginal atrophy is one of the relatively common problems in menopausal ages and a major health concern in this group of women. Several studies have been done in the field of herbal medicine in this subject, but different findings have been reported on the efficacy of these methods. This study was performed aimed to review the studies on the effect of herbal medicines on vaginal atrophy in postmenopausal women. Method(s): In this systematic review and meta-analysis, published articles in databases of PubMed, Scopus, Magiran, Cochrane, web of science, SID and Google scholar were reviewed between 2000-2020 using English key words of "vaginal Atrophy, vaginal Atrophy treatment, clinical trial, herbal medicine, complementary medicine, traditional medicine". Data were analyzed using STATA software (version 11) in %95 confidence interval. Odds ratio index and Peto method were used to combine studies and perform meta-analysis. Result(s): Meta-analysis results showed that in all studies, herbal intervention improved the symptoms of vaginal atrophy (P<0.001). So that the odds of improving itching, dryness and burning in the intervention group compared to the control group was (OR=12.53, %95 CI: 5.82-26.98), (OR=7.21, %95 CI: 4.72-11.02), and (OR=18.56, %95 CI: 8.94-38.55), respectively. Also, the odds of improving dyspareunia, improving maturity index of vaginal cells and lowering vaginal PH in the intervention group compared to the control group was (OR=25.38, %95 CI: 13.79-46.69), (OR=24.30, %95 CI: 13.61-43.37) and (OR=23.30, %95 CI: 13.05-41.59), respectively. Conclusion(s): Based on meta-analysis results, the effect of using herbal medicines on vaginal atrophy in postmenopausal women is statistically significant and the use of herbal remedies can be a good substitute for chemical drugs, because this method is accepted in postmenopausal women more than chemical drugs due to the side effects of hormone therapy.Copyright © 2021, Mashhad University of Medical Sciences. All rights reserved.

Saldanha, I. J., et al. (2023). "Delivery Strategies for Postpartum Care: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 142(3): 529-542.
	OBJECTIVE:To systematically review the effects of postpartum health care-delivery strategies on health care utilization and maternal outcomes.DATA SOURCES:We searched Medline, EMBASE, CENTRAL, CINAHL, and ClinicalTrials.gov for studies in the United States or Canada from inception to November 16, 2022.METHODS OF STUDY SELECTION:We used duplicate screening for studies comparing health care-delivery strategies for routine postpartum care on health care utilization and maternal outcomes. We selected health care utilization, clinical, and harm outcomes prioritized by stakeholder panels.TABULATION, INTEGRATION, AND RESULTS:We found 64 eligible studies (50 randomized controlled trials, 14 nonrandomized comparative studies; N=543,480). For general postpartum care, care location (clinic, at home, by telephone) did not affect depression or anxiety symptoms (low strength of evidence), and care integration (by multiple types of health care professionals) did not affect depression symptoms or substance use (low strength of evidence). Providing contraceptive care earlier (compared with later) was associated with greater implant use at 6 months (summary effect size 1.36, 95% CI 1.13-1.64) (moderate strength of evidence). Location of breastfeeding care did not affect hospitalization, other unplanned care utilization, or mental health symptoms (all low strength of evidence). Peer support was associated with higher rates of any or exclusive breastfeeding at 1 month and any breastfeeding at 3-6 months (summary effect size 1.10-1.22) but not other breastfeeding measures (all moderate strength of evidence). Care by a lactation consultant was associated with higher breastfeeding rates at 6 months (summary effect size 1.43, 95% CI 1.07-1.91) but not exclusive breastfeeding (all moderate strength of evidence). Use and nonuse of information technology for breastfeeding care were associated with comparable rates of breastfeeding (moderate strength of evidence). Testing reminders for screening or preventive care were associated with greater adherence to oral glucose tolerance testing but not random glucose or hemoglobin A1c testing (moderate strength of evidence). CONCLUSION(S):Various strategies have been shown to improve some aspects of postpartum care, but future research is needed on the most effective care delivery strategies to improve postpartum health.SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42022309756.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Saldanha, I. J., et al. (2023). Postpartum Care up to 1 Year After Pregnancy: A Systematic Review and Meta-Analysis.
	OBJECTIVES: This systematic review assesses postpartum care for individuals up to 1 year after pregnancy. We addressed two Key Questions (KQs) related to the comparative effectiveness and harms of: (1) alternative strategies for postpartum healthcare delivery and (2) extension of postpartum health insurance coverage. DATA SOURCES AND REVIEW METHODS: We searched Medline®, Embase®, Cochrane CENTRAL, CINAHL®, and ClinicalTrials.gov from inception to November 16, 2022, to identify comparative studies in the United States and Canada (for KQ 1) and in the United States (for KQ 2). We extracted study data into the Systematic Review Data Repository Plus (SRDR+; https://srdrplus.ahrq.gov). We assessed the risk of bias and evaluated the strength of evidence (SoE) using standard methods. The protocol was registered in PROSPERO (registration number CRD42022309756). RESULTS: We included 50 randomized controlled trials (RCTs) and 14 nonrandomized comparative studies (NRCSs) for KQ 1 and 28 NRCSs for KQ 2. Risk of bias was moderate to high for most RCTs and all NRCSs. KQ 1: Regarding where healthcare is provided, for general postpartum care (6 studies), whether the visit is at home/by telephone or at the clinic may not impact depression or anxiety symptoms (low SoE). For breastfeeding care (8 studies), whether the initial visit is at home or at the pediatric clinic may not impact depression symptoms up to 6 months postpartum, anxiety symptoms up to 2 months, hospital readmission up to 3 months (summary relative risk [RR] 1.38, 95% confidence interval [CI] 0.90 to 2.13; 4 studies), or other unplanned care utilization up to 2 months (low SoE, all outcomes). Regarding how care is provided, for general postpartum care (4 studies), integration of care (i.e., care provided by multiple types of providers) may not impact depression symptoms or substance use up to 1 year (low SoE). Regarding when care is provided, for contraceptive care (9 studies), compared with later contraception, earlier contraception start is probably associated with comparable continued IUD use at 3 and 6 months but greater implant use at 6 months (summary RR 1.36, 95% CI 1.13 to 1.64; 2 RCTs) (moderate SoE). Regarding who provides care, for breastfeeding care (19 studies), compared with no peer support, peer support is probably associated with higher rates of any breastfeeding at 1 month (summary effect size [ES] 1.13, 95% CI 1.03 to 1.24; 4 studies) and 3 to 6 months (summary ES 1.22, 95% CI 1.06 to 1.41; 4 studies) and of exclusive breastfeeding at 1 month (summary ES 1.10, 95% CI 1.02 to 1.19; 6 studies) but probably yields comparable rates of exclusive breastfeeding at 3 months and nonexclusive breastfeeding at 1 and 3 months (all moderate SoE). Compared with no lactation consultant, breastfeeding care by a lactation consultant is probably associated with higher rates of any breastfeeding at 6 months (summary ES 1.43, 95% CI 1.07 to 1.91; 3 studies) but not at 1 month or 3 months (all moderate SoE). Lactation consultant care may not be associated with rates of exclusive breastfeeding at 1 or 3 months (moderate SoE). Regarding coordination/management of care, provision of reminders for testing is probably associated with greater adherence to oral glucose tolerance testing up to 1 year postpartum but not random glucose testing or hemoglobin A1c testing (moderate SoE). Regarding use of information or communication technology (IT; 8 studies), IT use for breastfeeding care is probably associated with comparable rates of any breastfeeding at 3 months and 6 months and of exclusive breastfeeding at 3 months (all moderate SoE). Because of sparse evidence, inconsistent results, and/or the lack of reporting of prioritized outcomes, no conclusions related to interventions targeting healthcare providers are feasible (4 studies). KQ 2: Regarding health insurance (28 studies), more comprehensive health insurance is probably associated with greater attendance at postpartum visits (moderate SoE) and may be associated with fewer preventable readmissions and emergency room vis ts (low SoE). CONCLUSION: Most studies included in this systematic review enrolled predominantly healthy postpartum individuals. Researchers should therefore design studies that, either entirely or in part, enroll individuals at high risk of postpartum complications due to chronic conditions, pregnancy-related conditions, or incident or newly diagnosed conditions. New high-quality research is needed, especially for interventions targeting healthcare providers and the impact of more comprehensive or extended health insurance on postpartum health. Patient-reported outcomes, such as quality of life, should also be reported. Researchers should report separate data for various population subgroups, which could help close gaps in health outcomes among the races of postpartum individuals in the United States.

Salehi-Pourmehr, H., et al. (2023). "Is sacral neuromodulation effective and safe in pregnancy? A systematic review." Neurourology and Urodynamics 42(6): 1329-1343.
	Objective: We systematically assessed all available evidence on the efficacy and safety of sacral neuromodulation (SNM) in pregnancy.; Methods: On September 2022, a thorough search was done on Ovid, PubMed, Scopus, ProQuest, Web of Science, and The Cochrane Library. We chose studies that included pregnant women who had SNM previously. Two authors independently evaluated the quality of the study using a standardized tool of JBI. Studies were given a risk of bias rating of low, moderate, or high. Given the descriptive nature of this study, we utilized descriptive statistics to report demographic and clinical features. For continuous variables, we used mean and standard deviation, and for dichotomous data, we used frequencies and percentages.; Results: Out of 991 abstracts screened, only 14 studies met our inclusion criteria and were included in the review. Overall, the quality of the evidence available from the literature is low based on the design of the included studies. Fifty-eight women, including 72 pregnancies, had SNM. The indication of SNM implantation was filling phase disorders in 18 cases (30.5%), voiding dysfunction in 35 women (59.3%), IC/BPS in two cases (3.5%), and fecal incontinence. In 38 pregnancies (58.5%), the SNM status was ON during pregnancy. Forty-nine cases delivered a full-term baby (75.4%), 12 cases had pre-term labor (18.5%), two miscarriages, and two postterm pregnancies happened. The most complications in patients with devices were urinary tract infection in 15 women (23.8%), urinary retention in six patients (9.5%), and pyelonephritis in two cases (3.2%). The findings revealed that when the device was deactivated, 11 cases out of the 23 patients (47.8%) had full-term pregnancies, while in ON status, 35 out of the 38 pregnant women (92.1%) had full-term pregnancies. Nine preterm labors in OFF (39.1%), and two in ON status (5.3%) were recorded. The results revealed that this difference was statistically significant (p = 0.002), and those who turned SNM of them off had more preterm labor. Although the studies reported all neonates had a healthy status, two children had chronic motor tic problems and a pilonidal sinus in a case with an active SNM in pregnancy. However, there was no association between the SNM status and pregnancy or neonatal complications (p = 0.057).; Conclusion: SNM activation in pregnancy seems safe and effective. The choice of whether to activate or deactivate SNM should be made on an individual basis given the current SNM evidence. (© 2023 Wiley Periodicals LLC.)

Salehi-Pourmehr, H., et al. (2020). "Does aromatherapy with lavender affect physical and psychological symptoms of menopausal women? A systematic review and meta-analysis." Complementary Therapies in Clinical Practice 39: 101150.
	Objectives: The objective of this review was to evaluate systematically the effectiveness of Lavender aromatherapy on physical and psychological symptoms in menopausal women.; Methods: A comprehensive systematic literature search in the electronic databases including the Cochrane Library, MEDLINE (PubMed), Ovid, Embase, Scopus, ProQuest, Web of science, and Google scholar, as well as Magiran, SID, and Irandoc for Persian literature review up to January 2020. All Randomized controlled trials, and quasi-experimental studies that evaluated the impact of aromatherapy with lavender alone or in combination with other aromas on physical and psychological symptoms in menopausal women were included in this systematic review.; Results: Sixteen interventional studies consisted of 1092 postmenopausal women included in systematic review. Eight of eligible studies with 493 participants included in meta-analysis. There were significant between group differences in menopausal symptoms (standardized mean difference (SMD) = -1.39, 95% confidence interval (CI): 1.98 to -0.80, I 2 = 76%; four trials, 236 participants); sleep quality score (SMD = -2.16, 95%CI: -3.77 to -0.54, I 2 = 95%; three studies, 199 participants); systolic blood pressure (MD = -5.34 mmHg, 95% CI: -7.40 to -3.29, I 2 = 10%; two study, 114 participants); diastolic blood (MD = -5.06 mmHg, 95% CI: -7.55 to -2.57, I 2 = 0%; two study, 114 participants). Aromatherapy had positive effect on sexual function, self-esteem, anxiety, hot flash, but it had negative impact on triglyceride and high density lipoprotein compared to placebo (p < 0.05).; Conclusions: Aromatherapy with Lavender in postmenopausal women may cause an improvement in most of physical and psychological symptoms. Further high quality studies especially with focus on the adverse events are suggested globally.; Competing Interests: Declaration of competing interest Authors declare no conflict of interests for this study. (Copyright © 2020. Published by Elsevier Ltd.)

Salento University, o. (2021). Effects of Fasting Mimicking Diet (FMD) in Women With Polycystic Ovary Syndrome (PCOS).
	No Results Available Dietary Supplement: Fasting mimicking diet Restoration of menstrual regularity|Improvement of blood glucose values (mg / dl)|Improvement of blood insulinemic values (µU/mL)|Improvement of blood glycated hemoglobin (%)|Improvement of blood LDL, HDL, total cholesterol and triglycerides (mg/dl)|Improvement in plasma sexual hormones|Improvemet in the PCR value|Improvement in depression syntoms evaluated bu Basic Self- Esteem Scale and improvement in quality of life, assessed by WHOQOL-BREF test Female Not Applicable 100 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: None (Open Label)|Primary Purpose: Treatment VERBALE N° 56 January 1, 2025

Salinas-Asensio María Del, M., et al. (2022). "'Physio-EndEA' Study: A Randomized, Parallel-Group Controlled Trial to Evaluate the Effect of a Supervised and Adapted Therapeutic Exercise Program to Improve Quality of Life in Symptomatic Women Diagnosed with Endometriosis." International Journal of Environmental Research and Public Health 19(3).
	Aim: The 'Physio-EndEA' study aims to explore the potential benefits of a therapeutic exercise program (focused on lumbopelvic stabilization and tolerance to exertion) on the health-related quality of life (HRQoL) of symptomatic endometriosis women.; Design: The present study will use a parallel-group randomized controlled trial design.; Methods: A total of 22 symptomatic endometriosis women will be randomized 1:1 to the Physio-EndEA or usual care groups. The 'Physio-EndEA' program will consist of a one-week lumbopelvic stabilization learning phase followed by an eight-week phase of stretching, aerobic and resistance exercises focused on the lumbopelvic area that will be sequentially instructed and supervised by a trained physiotherapist (with volume and intensity progression) and adapted daily to the potential of each participant. The primary outcome measure is HRQoL. The secondary outcome measures included clinician-reported outcomes (pressure pain thresholds, muscle thickness and strength, flexibility, body balance and cardiorespiratory fitness) and patient-reported outcomes (pain intensity, physical fitness, chronic fatigue, sexual function, gastrointestinal function and sleep quality).; Discussion: Findings of this study will help to identify cost-effective non-pharmacological options (such as this exercise-based intervention) that may contribute to the improvement of HRQoL in symptomatic endometriosis women.

Sallée, C., et al. (2023). "Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery." Journal of Gynecology Obstetrics and Human Reproduction 52(7): 102621.
	Objective: Safety of the uterine manipulator (UM) within endometrial cancer (EC) surgery is being questioned. Its use might be one of the issues for potential tumor dissemination during the procedure, especially in the case of uterine perforation (UP). No prospective data on this surgical complication, nor on the oncological consequences exist. The aim of this study was to assess the rate of UP while using UM when performing surgery for EC and the impact of UP on the choice of adjuvant treatment.; Methods: We conducted a prospective single-center cohort study from November 2018 to February 2022, considering all EC cases surgically treated by a minimally invasive approach with the help of a UM. Demographic, preoperative, postoperative and adjuvant treatment corresponding to the included patients were collected and comparatively analyzed according to the absence or presence of a UP.; Results: Of the 82 patients included in the study, 9 UPs (11%) occurred during surgery. There was no significant difference in demographics and disease characteristics at diagnosis that may have induced UP. The type of UM used or the approach (laparoscopic vs. robotic) did not influence the occurrence of UP (p = 0.44). No positive peritoneal cytology was found post hysterectomy. There was a statistically significantly higher rate of lymph-vascular space invasion within the perforation group, 67% vs. 25% in the no perforation group, p = 0.02. Two out of nine (22%) adjuvant therapies were changed because of UP. The median follow-up time for patients was 7.6 months (range 0.5-33.1 months). No recurrence was found in the UP group.; Conclusion: Our study found a uterine perforation rate of 11%. This information needs to be further integrated to consider the usefulness of MU for EC surgery.; Competing Interests: Declaration of Competing Interest None declared. (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Sally, K., et al. (2021). "Conventional GnRH antagonist protocols VS agonist protocols in Polycystic ovary syndrome patients undergo IVF/ICSI: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Salo, H., et al. (2023). "Long-term results of a prospective randomized trial comparing tension-free vaginal tape versus transobturator tape in stress urinary incontinence." International Urogynecology Journal 34(9): 2249-2256.
	Introduction and hypothesis: This study was aimed at investigating the long-term effectiveness of minimally invasive mid-urethral sling (MUS) surgery and at comparing the outcomes between retropubic (tension-free vaginal tape, TVT) and transobturator tape (TOT) methods in the treatment of stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) with a predominant stress component in a long-term follow-up of a randomized controlled trial. Method(s): This work is a long-term follow-up study of a previous prospective randomized trial conducted in the Department of Obstetrics and Gynecology at Oulu University Hospital between January 2004 and November 2006. The original 100 patients were randomized into the TVT (n=50) or TOT (n=50) group. The median follow-up time was 16 years, and the subjective outcomes were evaluated using internationally standardized and validated questionnaires. Result(s): Long-term follow-up data were obtained from 34 TVT patients and 38 TOT patients. At 16 years after MUS surgery, the UISS significantly decreased from a preoperative score in the TVT (11.88 vs 5.00, p<0.001) and TOT (11.05 vs 4.95, p<0.001) groups, showing a good long-term success of the MUS surgery in both groups. In comparing the TVT and TOT procedures, the subjective cure rates did not differ significantly between the study groups in long-term follow-up according to validated questionnaires. Conclusion(s): Midurethral sling surgery had good long-term outcomes in the treatment of SUI and MUI with a predominant stress component. The subjective outcomes of the TVT and TOT procedures were similar after a 16-year follow-up.Copyright © 2023, The Author(s).

Salvatore, S., et al. (2023). "Laser versus sham for genitourinary syndrome of menopause: A randomised controlled trial - Some crucial criticalities." BJOG: An International Journal of Obstetrics and Gynaecology 130(13): 1697-1698.
	
Sam, E., et al. (2022). "Is biofeedback-assisted pelvic floor muscle training superior to pelvic floor muscle training alone in the treatment of dysfunctional voiding in women? A prospective randomized study." International braz j urol : official journal of the Brazilian Society of Urology 48(3): 501-511.
	PURPOSE: To compare the effectiveness of biofeedback-assisted pelvic floor muscle training (PFMT) and PFMT alone on voiding parameters in women with dysfunctional voiding (DV). MATERIALS AND METHODS: The patients in group 1 (34 patients) were treated with biofeedback-assisted PFMT, and the patients in group 2 (34 patients) were treated with PFMT alone for 12 weeks. The 24-hour frequency, average voided volume, maximum urine flow rate (Qmax), average urine flow rate (Qave), post-void residual urine volume (PVR), and the validated Turkish Urogenital Distress Inventory (UDI-6) symptom scores were recorded before and after 12 weeks of treatment. RESULTS: At the end of treatment sessions, the Qmax and Qave values of the patients in group 1 were significantly higher than those in group 2, and the PVR in the patients in group 1 was significantly lower than those in group 2 (p=.026, .043, and .023, respectively). The average UDI-6 symptom scores of the patients in group 1 were significantly lower than those in group 2 (p=.034). Electromyography activity during voiding, in group 1 was significantly lower than in group 2 (41.2 vs. 64.7, respectively, p=.009). CONCLUSION: Biofeedback-assisted PFMT is more effective than PFMT alone in improving clinical symptoms, uroflowmetry parameters, and EMG activity during voiding.

Samaa, M., et al. (2022). "A systematic review of endometriosis recurrence: towards a comprehensive framework."
	
Samami, E., et al. (2023). "Pain-focused psychological interventions in women with endometriosis: A systematic review." Neuropsychopharmacology reports 43(3): 310-319.
	Aims: As a chronic inflammatory disease, endometriosis (EMS) is often associated with pain affecting different aspects of women's lives. Up to now, a wide variety of interventions have been implemented to alleviate pain in patients with this condition, including pharmacological, surgical, and rarely non-pharmacological ones. Against this background, this review aimed to investigate pain-focused psychological interventions among EMS women.; Methods: A systematic review of the articles published in this field was conducted through a comprehensive search on the databases of Scopus, PubMed, MEDLINE, Web of Science, ScienceDirect, the Cochrane Library, PsycINFO, Google Scholar, and Scientific Information Database (SID). The quality of studies was then assessed by the Jadad Scale.; Results: In total, 10 articles were entered into this systematic review. The findings further revealed that the pain-focused psychological interventions in patients with EMS were cognitive-behavioral therapy (CBT) (n = 2), mindfulness therapy (n = 4), yoga (n = 2), psychoeducation (n = 1), and progressive muscle relaxation (PMR) training (n = 1). Besides, the findings established that all the given interventions had improved and reduced pain in women living with this condition. Moreover, five articles were of good quality based on the Jadad Scale.; Conclusion: The study results demonstrated that all the listed psychological interventions had affected pain relief and improvement in women suffering from EMS. Considering the limited number of studies in this field and the fact that there were only five articles endowed with good quality, more high-quality studies could provide stronger evidence to support the implementation of the mentioned interventions influencing pain in patients. (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Samawi, L., et al. (2021). "Effectiveness of psychological interventions to reduce alcohol consumption among pregnant and postpartum women: a systematic review." Archives of Women's Mental Health 24(4): 557-568.
	This study aims to synthesise the available evidence on psychological interventions to reduce alcohol consumption among pregnant and postpartum women. Six electronic databases were searched to identify controlled studies targeting pregnant and postpartum women who drink or are at risk of drinking due to previous patterns of alcohol use. Controlled quantitative studies such as randomised controlled trials and quasi-experimental studies were included. The search was limited to peer-reviewed articles in English. The methodological quality of studies was assessed using the Cochrane risk of bias tool. A narrative synthesis of the findings was conducted. In total, 12,610 records were screened, and 11 studies were eligible for inclusion (9 with pregnant women, 2 with postpartum women). All studies were randomised controlled trials. Five studies had positive or partially positive primary outcomes of reductions in drinking or abstinence, and their interventions ranged from multi-session brief interventions to self-help manuals based on cognitive behavioural components. All studies showed considerable methodological limitations. Psychological interventions may be effective in promoting abstinence or reducing alcohol consumption among pregnant and postpartum women. Interventions that demonstrated some efficacy showed higher level of engagement with pregnant women compared to studies which delivered interventions in a single session. Paucity of evidence, inconsistency of outcomes, large heterogeneity in the interventions and methodological weaknesses limit the ability to make final conclusions about the overall effectiveness of these interventions. Findings highlight the need for better quality research on this topic.

Sami, S., et al. (2021). "Systematic review of the effectiveness and techniques of transcutaneous tibial nerve stimulation (TTNS) for adults with overactive bladder syndrome (OAB)."
	
Samit, G. and S. Binayak (2021). "A meta-analysis on the effect of sodium glucose cotransporter-2 inhibitor (SGLT-2 i) on metabolic parameters in patients with polycystic ovary syndrome (PCOS)."
	
Sampogna, G., et al. (2023). "Pelvic floor muscle training: Novel versus traditional remote rehabilitation methods-A systematic review and meta-analysis on their effectiveness for women with urinary incontinence." Neurourology and Urodynamics.
	
Samy, A., et al. (2020). "Perioperative nonhormonal pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy: a systematic review and network meta-analysis." Fertility and Sterility 113(1): 224.
	Objective: To synthesize evidence on the most effective pharmacological interventions for bleeding reduction during open and minimally invasive myomectomy.; Design: Systematic review and network meta-analysis of randomized controlled trials (RCTs).; Setting: Not applicable.; Patients: Trials assessing efficacy of pharmacological interventions during different types of myomectomy.; Interventions: Misoprostol, oxytocin, vasopressin, tranexamic acid (TXA), epinephrine, or ascorbic acid.; Main Outcome Measures: Intraoperative blood loss and need for blood transfusion.; Results: The present review included 26 randomized control trials (RCTs) (N = 1627). For minimally invasive procedures (9 RCTs; 474 patients), network meta-analysis showed that oxytocin (mean difference [MD] -175.5 mL, 95% confidence interval [CI] -30.1.07, -49.93), ornipressin (MD -149.6 mL, 95% CI - 178.22, -120.98), misoprostol, bupivacaine plus epinephrine, and vasopressin were effective in reducing myomectomy blood loss, but the evidence is of low quality. Ranking score of treatments included in subgroup analysis of minimally invasive myomectomy showed that oxytocin ranked first in reducing blood loss, followed by ornipressin. For open myomectomy (17 RCTs; 1,153 patients), network meta-analysis showed that vasopressin plus misoprostol (MD -652.97 mL, 95% CI - 1113.69, -174.26), oxytocin, TXA, and misoprostol were effective; however, the evidence is of low quality. Vasopressin plus misoprostol ranked first in reducing blood loss during open myomectomy (P = .97).; Conclusion: There is low-quality evidence to support uterotonics, especially oxytocin, and peripheral vasoconstrictors as effective options in reducing blood loss and need for blood transfusion during minimally invasive myomectomy. Oxytocin is the most effective intervention in minimally invasive myomectomy. For open myomectomy, a combination of uterotonics and peripheral vasoconstrictors is needed to effectively reduce blood loss. (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Sanaee May, S., et al. (2019). "Urinary tract infection prevention after midurethral slings in pelvic floor reconstructive surgery: A systematic review and meta-analysis." Acta Obstetricia et Gynecologica Scandinavica 98(12): 1514-1522.
	Introduction: Synthetic midurethral slings are the most common procedures currently performed for stress urinary incontinence in women. Infection is a frequent complication of urogynecologic surgery. We performed a systematic review and meta-analysis to identify interventions that successfully prevent infections, including urinary tract infection (UTI) and/or bacteriuria, compared with no intervention, in women undergoing midurethral sling surgery with or without concomitant pelvic reconstructive procedures for prolapse.; Material and Methods: The primary outcome was the development of any infection post-midurethral sling placement in women. MEDLINE, Embase, CINAHL and the Cochrane Library were searched for comparative studies from inception to July 2017, with no language restrictions. We used search terms related to midurethral sling, infections and infection-reduction interventions. Two independent reviewers abstracted data and assessed study quality. Pooled effect size estimates were calculated. We conducted meta-analysis of eligible studies. A protocol for this review has been registered and can be accessed online (http://hdl.handle.net/2429/64731).; Results: We identified seven eligible studies of infection risk-reducing interventions; all focused on UTIs. Only one study assessed preoperative antibiotics with midurethral sling alone and was halted early because of low UTI rates. All other studies (three randomized control trials and three observational studies) examined whether postoperative antibiotics decrease UTI/bacteriuria rates after midurethral sling with or without reconstructive procedures for pelvic organ prolapse and using bladder catheterization postoperatively. Due to considerable clinical heterogeneity, we only combined four studies for meta-analysis. Postoperative oral prophylactic nitrofurantoin showed no significant benefit in reducing UTI/bacteriuria in women post-midurethral sling with or without concomitant reconstructive pelvic surgery and the need for bladder catheterization, when compared with the reference group (pooled relative risk 0.73, 95% confidence interval [CI] 0.42-1.25).; Conclusions: Based on the best available evidence, postoperative oral nitrofurantoin is not effective at reducing UTI/bacteriuria rates in catheterized women after midurethral sling with or without concomitant pelvic reconstructive surgery for prolapse. For midurethral sling alone, preoperative antibiotic prophylaxis may not be needed for UTI prevention. (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Sanborn Rachel, E., et al. (2022). "Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors." Journal for Immunotherapy of Cancer 10(8).
	Background: Phase 1/2 dose-escalation and expansion study evaluating varlilumab, a fully human agonist anti-CD27 mAb, with nivolumab in anti-PD-1/L1 naïve, refractory solid tumors.; Methods: Phase 1 evaluated the safety of varlilumab (0.1-10 mg/kg) with nivolumab (3 mg/kg) administered once every 2 weeks. Phase 2 evaluated varlilumab regimens (3 mg/kg once every 2 weeks, 3 mg/kg once every 12 weeks, and 0.3 mg/kg once every 4 weeks) with nivolumab 240 mg once every 2 weeks in tumor-specific cohorts. Primary objective was safety; key clinical endpoints included objective response rate (ORR) and overall survival rate at 12 months (OS12) (glioblastoma (GBM) only). Exploratory objectives included determination of effects on peripheral blood and intratumoral immune signatures.; Results: 175 patients were enrolled (36 in phase 1 and 139 in phase 2). Phase 1 dose-escalation proceeded to the highest varlilumab dose level without determining a maximum tolerated dose. In phase 2, ORR were ovarian 12.5%, squamous cell carcinoma of the head and neck 12.5%, colorectal cancer 5%, and renal cell carcinoma 0%; GBM OS12 was 40.9%. Increased tumor PD-L1 and intratumoral T cell infiltration were observed in ovarian cancer patients, with increases of ≥5% associated with better progression-free survival. The most common treatment related adverse events were fatigue (18%), pruritus (16%), and rash (15%).; Conclusion: Varlilumab and nivolumab were well tolerated, without significant toxicity beyond that expected for each agent alone. Clinical activity was observed in patients that are typically refractory to anti-PD-1 therapy, however, overall was not greater than expected for nivolumab monotherapy. Treatment was associated with proinflammatory changes in the tumor microenvironment, particularly in ovarian cancer where the changes were associated with better clinical outcomes.; Trial Registration Number: NCT02335918.; Competing Interests: Competing interests: RES: none. MP: none. MC: reports grants from Bristol Myers Squibb for projects outside this manuscript, personal fees from Merck, InCyte, Moderna, ImmunoCore, and AstraZeneca. Additionally, she has an immediate family member who is employed at Bristol Myers Squibb and receives unvested stock as a form of compensation. AW: none. BS: none. OR: research support from Merck. Speaker for activities supported by educational grants from BMS and Merck. Consultant for Merck, Celgene, Five Prime, GSK, Bayer, Roche/Genentech, Puretech, Imvax, Sobi. In addition, Dr Rahma has patent ‘Methods of using pembrolizumab and trebananib’ pending. DCC: consultant for Nektar, Werewolf, Pfizer, and HUYA. NR: was an employee of Herbert Irving Comprehensive Cancer Center, Columbia University, NY, USA when the analysis was conducted and is a stockholder of Gritstone bio and Synthekine and is a current employee of Synthekine. MZ: consulting fees from Alkermes, PIO Therapeutics, Iovance, Biontech DSMC, Regeneron, Merck, Kadmon-Sanofi, Incyte, Dragonfly, Evoveimmune, Rootpath, Anaptys, Numab, Biond, Adaptimmune, Bristol-Myers, Simcha, Verastem, Pfizer, Innate Pharma, Pierre-Fabre, Nextcure, Alligator, Ocellaris-Lilly, Immunoscore, Glaxo Smith Kline, Adagene, Asher, Kanaph, iTEOS, Genocea, Trillium, Sapience, Targovax, Molecular Partners, Ontario Institute for Cancer Research, Jazz Pharmaceuticals, Gilead, Tessa, Stcube, Oncosec, Astra Zeneca, Agenus, Idera, Apexigen, Rubius, Genetech-Roche, Boston Pharmaceuticals, and Servier. Stock or stock options for Adaptive Biotechnologies, Amphivena, Intensity, Actym, Nanobot, Johnson and Johnson, Glaxo-Smith Kline, Evolveimmune, Nextcure, Torque Repertoire, Oncohost, Rootpath, and Asher. JL: none. JEB: grants to the University of Arizone for cancer-related clinical research from Astra Zeneca, Aveo, Celldex, CUE, Lilly, and Novartis. RB: none. AS: BMS speaker bureau. AJ: reports no relevant conflicts. AJ owns stock/options on Champions Oncology and Suvica. AJ institution has contracts for trials where AJ is local PI with Pfizer, Merck, SQZ, Moderna, Iovance, Khar Bio harma, DebioPharm, Cantargia and Sanofi. DR: Research support (paid to DFCI): Acerta Phamaceuticals; Agenus; Bristol-Myers Squibb; Celldex; EMD Serono; Enterome; Epitopoietic Research Coorporatioin; Incyte; Inovio; Insightec; Novartis; Omniox; Tragara. Advisory/consultation (paid to Dr Reardon): Abbvie; Advantagene; Agenus; Agios; Amgen; AnHeart Therapeutics; Avita Biomedical, Inc., Bayer; Boston Biomedical; Boehringer Ingelheim; Bristol-Myers Squibb; Celldex; Deciphera; Del Mar Pharma; DNAtrix; Ellipses Pharma; EMD Serono; Genenta; Genentech/Roche; Hoffman-LaRoche, Ltd; Imvax; Inovio; Kintara; Kiyatec; Medicenna Biopharma, Inc.; Merck; Merck KGaA; Monteris; Neuvogen; Novartis; Novocure; Oncorus; Oxigene; Regeneron; Stemline; Sumitono Dainippon Pharma; Pyramid; Taiho Oncology, Inc.; Vivacitas Oncology, Inc., Y-mabs Therapeutics. ThK: none. FI: consulting or Advisory Role: Novocure, Regeneron, Abbvie, Merck, Tocagen, Alexion, Guidepoint Global, Gennao Bio, Xcures, Innovation Spec, Medtronic, MassiveBio, Kiyatec, MimiVax. Speakers’ Bureau: Prime Oncology; Institutional Research Funding: Merck, Bristol-Myers Squibb, Tocagen, FORMA Therapeutics, Celldex, Northwest Biotherapeutics, Sapience Therapeutics, Novocure. Travel, Accommodations, Expenses: Oncoeutics. DSS: employee of AstraZeneca and have stock options with the same. JBA: Honoraria from Bristol Myers Squibb, Pfizer/EMD Serono, and Astellas/Seattle Genetics. Meeting and travel support from EMD Serono and Bristal Myers Squibb. Participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, Merck, EMD Serono, Astellas, Seattle Genetics, Immunomedics, AZD, Aveo, Exelixis, Janssen, Pfizer/Myovant. TRH: employee of Celldex and own Celldex stock. TR: was an employee of Celldex at the time the study was conducted. MY: employee of Celldex and owns Celldex stock. TiK: employee of Celldex and owns Celldex stock. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sanchez, S., et al. (2021). "Treatment of vulvar pain caused by atrophy: A systematic review of clinical studies." Clinical and Experimental Obstetrics and Gynecology 48(4): 800-805.
	Background: The signs and symptoms of the genitourinary syndrome of menopause are well established, and there is extensive knowledge with high scientific evidence about the response that vaginal and urinary tissues present to various treatments. However, this does not usually apply to the vulva in general, or any of its structures in particular, since it is included in the term vulvovaginal. The aim of this review is to improve knowledge about the vulva and to improve symptoms in women who experience vulvar pain associated with atrophy. Method(s): The study was registered at PROSPERO (registration number CRD42020172102). We also assessed the quality of evidence for each outcome of interest according to the GRADE criteria. Result(s): We systematically reviewed eight studies: Four with ospemifene, a pilot study with prasterone, a study using a combination of estrogens and androgens, another study that used CO2 laser surgery and another with application of 0.005% estriol gel to the vulvar vestibule. Meta-analysis was not possible due to the heterogeneity and small sample size of the included studies. Ospemifene orally, at a dose of 60 mg daily for a time period of between 60 days and 20 weeks, report preliminary data showing improvements of vulvar and vestibule trophism. Prasterone showed in an open-label prospective survey, improve in the vulvoscopic results and dyspareunia, in women that used vaginal prasterone. The combination of estriol and testosterone propionate 2% for 12 weeks showed an improve of Vulvar pain due to atrophy (VPA) and dyspareunia in a descriptive prospective survey. A retrospective analysis of 79 postmenopausal women presenting vulvar pain who were treated with CO2 laser or laser plus ospemifene, showed that vestibular dryness was significantly lower in the ospemifene + laser group compared with the laser treatment group (- 87% vs -34%, respectively). Finally, we also included a prospective open-label survey using for a 12-week treatment period, a fingertip to apply 0.25 g of vaginal gel containing 25 mug of estriol to the vulvar vestibule daily for three weeks and then twice weekly for up to 12 weeks. Dyspareunia improved or was cured (score<=1) by week 12 in 81.4% of patients. Discussion(s): All the therapeutic strategies show improvement in vulvar pain, but not all are papers with the same scientific evidence. The best quality studies are those carried out with ospemifene since they are randomized and placebo controlled studies. However, the improvement demonstrated by prasterone, estriol, the combination of estrogens and androgens, as well as the CO2 laser, although they do not have high-quality studies, should not be ruled out since they promise good results and the user profiles they represent, allow more women to be reached. We propose a therapeutic strategy where the patient expresses her preferences, based on previous experiences and treatments already carried out. In addition, we believe that correctly informing patients about VPA can help a better therapeutic response. More investigation about the vulvar treatments is needed.Copyright © 2021 The Author(s).

Sánchez-Delgado, J. C., et al. (2023). "Combined effect of physical exercise and hormone replacement therapy on cardiovascular and metabolic health in postmenopausal women: A systematic review and meta-analysis." Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 56: e12241.
	The cardioprotective effect of postmenopausal hormone replacement therapy (HRT) has been demonstrated in several studies. Similarly, physical exercise has yielded positive results. However, the effects of their combination remain inconclusive. This review describes the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We searched the Scopus, Web of Science, PubMed, and Embase databases and included randomized controlled trials published up to December 2021 on the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We identified 148 articles, of which only seven met the inclusion criteria (386 participants; 91 [23%] HRT + exercise; 104 [27%] HRT; 103 [27%] exercise; 88 [23%] placebo). The combined treatment further decreased systolic blood pressure (SBP) compared to the isolated effect of aerobic training (AT) (mean difference [MD]=-1.69; 95% confidence interval [CI]=-2.65 to -0.72, n=73). Nevertheless, it attenuated the decrease in diastolic blood pressure (DBP) (MD=0.78; 95%CI: 0.22-1.35, n=73), and the increase in peak oxygen consumption (VO2 peak) promoted by exercise (AT + HRT=2.8±1.4 vs AT + placebo=5.8±3.4, P=0.02). The combination of AT and oral HRT improved SBP. However, AT alone seemed to have a better effect on physical fitness and DBP in postmenopausal women.

Sánchez-Delgado Juan, C., et al. (2023). "Physical Exercise Effects on Cardiovascular Autonomic Modulation in Postmenopausal Women-A Systematic Review and Meta-Analysis." International Journal of Environmental Research and Public Health 20(3).
	Background: The cardioprotective effect of physical exercise has been demonstrated in several studies. However, no systematic or updated analysis has described the effects of physical exercise on cardiovascular autonomic modulation in postmenopausal women.; Aim: to describe the effects of physical exercise on cardiovascular autonomic modulation in postmenopausal women.; Methods: The Scopus, PubMed, and Embase databases were searched for randomized clinical trials published between January 2011 and December 2021, and regarding the effects of physical exercise on cardiovascular autonomic modulation in postmenopausal women. Two independent authors processed the citations. The methodological quality was evaluated using the PEDRo scale.; Results: Of the 91 studies identified, only 8 met the inclusion criteria, of which 7 had fair or poor methodological quality. The analyzed studies investigated the effects of functional training, whole-body vibration, muscular resistance, stretching, and aerobic exercises performed at home or at the gym. The majority of these exercise modalities showed improvements in heart-rate variability (HRV) indices and in the low-frequency band of blood pressure variability. The meta-analysis shows that exercise increased the standard deviation of instantaneous beat-to-beat variability (SD1) (mean difference (MD) = 3.99; 95% confidence interval (CI) = 1.22 to 6.77, n = 46; I 2 : 0%) and the standard deviation of long-term variability (SD2) (MD = 11.37; 95% CI = 2.99 to 19.75; n = 46; I 2 : 0%).; Conclusions: Aerobic exercise and some nonconventional training modalities may have beneficial effects on cardiovascular autonomic modulation in postmenopausal women. More high-quality studies are still needed to further confirm their efficacy and safety.

Sánchez-García, J. C., et al. (2023). "Physical Exercise and Dietary Supplementation in Middle-Aged and Older Women: A Systematic Review." Journal of Clinical Medicine 12(23).
	UNLABELLED: With the aging of the population in developed countries, the number of middle-aged and older women is progressively increasing. During this stage, women suffer from a number of signs and symptoms that could be reduced or treated with physical exercise and dietary supplements. The main objective of this study was to analyse the benefits of exercise and dietary supplements during menopause. MATERIALS AND METHODS: A systematic review of the scientific literature was performed according to the PRISMA 2020 protocol, searching the PubMed, Cochrane, Scopus, and WOS databases. Studies that met the inclusion criteria were assessed for methodological quality using the PEDro or AMSTAR-2 scales. RESULTS: The searches yielded a total of 104 results, of which 10 were selected, with methodological quality ranging from fair to excellent. Each article examined the combination of a dietary supplement plan versus a placebo; plus an exercise routine versus another routine or a sedentary lifestyle. The results showed the benefits of combining a nutritional supplementation plan with an exercise routine during menopause. CONCLUSIONS: The practice of weekly strength and endurance exercises, together with the consumption of certain dietary supplements, may be a good resource for coping with menopause in a healthy way.

Sánchez-Iglesias, J. L., et al. (2022). "Cost analysis of the enhanced recovery after surgery protocol applied in advanced ovarian cancer: A secondary outcome of the PROFAST trial." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 48(12): 2545-2550.
	Introduction: A randomised trial implementing Enhanced Recovery After Surgery (ERAS) for high complexity advanced ovarian cancer (AOC) surgery (PROFAST) demonstrated a reduction of median length of stay and hospital readmissions when compared to patients managed conventionally. One secondary objective was to determine if an ERAS pathway in the perioperative management of advanced ovarian cancer patients led to cost savings.; Material and Methods: Secondary objective of a prospective randomised trial of patients with suspected or diagnosed advanced ovarian cancer allocated to conventional or ERAS perioperative management, carried out at a referral centre from June 2014 to March 2018. Treatment was determined by a computer-generated random allocation system.; Methods: Gross counting was employed to estimate the cost of hospitalisation in wards, intensive care unit (ICU) and surgical care, while micro-costing was used to obtain image and laboratory test costs. Mean costs between trial arms were considered. Sensitivity analyses were performed.; Results: Ninety-nine patients (n = 50 ERAS group, n = 49 Conventional group) were included. Mean costs per patient were 10,719€ in the ERAS group and 11,028€ in the conventional group, leading to an average saving of 309€ per patient. These results were based on 96 patients, excluding 3 extreme outliers mainly related with very high ICU costs. Savings, which were significant for hospital ward costs (-33% total; 759€ per patient in first hospitalisation, and 914€ per partient/day of readmission) were found as robust in the sensitivity analysis.; Conclusions: Implementation of an ERAS pathway leads to cost savings when compared to conventional management after AOC surgery.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Sánchez-Iglesias, J. L., et al. (2021). "Importance of Enhanced Recovery After Surgery (ERAS) Protocol Compliance for Length of Stay in Ovarian Cancer Surgery." Annals of Surgical Oncology 28(13): 8979-8986.
	OBJECTIVES: Enhanced Recovery After Surgery (ERAS) programs include multiple perioperative care elements, which when implemented together are designed to improve recovery after surgery with subsequent reduction in hospital length of stay (LOS). The aim of this study is to examine the impact of ERAS protocol compliance on LOS in patients undergoing advanced ovarian cancer surgery within the context of a randomized clinical trial. METHODS: Patients were enrolled in a prospective, consecutive, interventional randomized clinical trial between June 2014 and March 2018. Women with either suspected or confirmed advanced ovarian cancer with International Federation of Gynecology and Obstetrics (FIGO) stages IIB-IVA and recurrent ovarian cancer, who underwent cytoreduction surgery, were randomly assigned to either a conventional management (CM) protocol or an ERAS protocol. Demographic items, preoperative clinical data, and surgical characteristics of patients were recorded, as were LOS and ERAS protocol compliance. Negative binomial regression was used to model the relation between length of stay and ERAS protocol compliance. RESULTS: We included 49 patients in the CM group and 50 patients in the ERAS group. The overall rate of ERAS compliance was 92%. We observed that increasing ERAS protocol compliance was associated with shorter median LOS, and in patients who underwent higher complex surgeries, the length of stay reduction was greater. CONCLUSION: This study identifies a correlation between increasing ERAS protocol compliance and decreasing LOS in ovarian cancer surgery. This finding underlines the necessity to implement as many ERAS protocol elements as possible to achieve optimal clinical outcome improvements.

Sánchez-Martínez, L., et al. (2021). "A Systematic Review of the Cardiometabolic Benefits of Plant Products Containing Mixed Phenolics and Polyphenols in Postmenopausal Women: Insufficient Evidence for Recommendations to This Specific Population." Nutrients 13(12).
	Menopause is characterized by endocrine and physiological changes and is often accompanied by increased body weight and cholesterol, glucose intolerance, and/or hypertension. These alterations are associated with increased risk for cardiovascular diseases (CVDs) and Type II diabetes mellitus (T2DM) that may be moderate by dietary plant phenolic compounds. In this review, we examine the current evidence of the impact of a variety of plant products (foods, extracts, beverages) rich in a mixture of phenolics and polyphenols on: (i) glucose and insulin levels; (ii) lipid profile; (iii) blood pressure; and (iv) biomarkers of inflammation and oxidative stress in postmenopausal women. We critically evaluate both the results of a range of intervention studies conducted in this specific subpopulation and the level of evidence supporting the benefits of consuming those products after the menopause. Overall, the current available evidence does not allow for specific dietary recommendations of these plant products rich in phenolics and polyphenols in this high-risk subpopulation. Our data show rather variable and small effects of the different products examined on the cardiometabolic biomarkers and further support the need to: (1) improve the quality of the study designs and data reporting; and (2) understand the variability in the response of the different biomarkers and establish clear differences between healthy and cardiometabolic disease levels.

Sánchez-Sánchez María, L., et al. (2020). "Mediterranean diet and health: A systematic review of epidemiological studies and intervention trials." Maturitas 136: 25-37.
	Diet is a crucial variable for a healthy life. A rapidly growing number of studies in recent years support the hypothesis that the Mediterranean diet (MedDiet) has a beneficial effect on certain body systems, but the highly varied objectives and quality of these publications warrants an updated assessment. In the present review we performed a comprehensive evaluation of current evidence on the impact of the MedDiet on human health, assessing its effect on the incidence or progression of the main non-communicable diseases and their intermediate outcomes and risk factors. We scrutinised the clinical evidence from observational studies and randomised controlled trials. Cardiovascular disease was the condition with most information. The MedDiet showed a general preventive effect, which was reproduced to varying degrees for certain intermediate cardiovascular outcomes such as blood pressure, lipids, obesity, metabolic syndrome and diabetes. Benefits were also found for several types of cancer, brain function (including cognition, mood and to a lesser extent Parkinson's disease) and mortality. The quality of the published evidence was, however, generally moderate or low. In conclusion, the MedDiet shows a favourable impact on health. General adoption of a MedDiet is concordant with current policies promoting healthy and sustainable nutrition worldwide. Nonetheless, more high-quality research is needed to improve the consistency of the findings. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sanders Ari, P., et al. (2020). "Reproductive Outcomes Following Uterine Artery Occlusion at the Time of Myomectomy: Systematic Review and Meta-analysis." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 42(6): 787.
	This investigation sought systematically to review and meta-analyze evidence on reproductive outcomes following uterine artery occlusion (UAO) at myomectomy. Databases searched included PubMed, EMBASE, Ovid MEDLINE, Web of Science, and ClinicalTrials.gov. Eligible studies included observational and randomized controlled trials in which patients underwent abdominal, laparoscopic, or robotic myomectomy and in which at least one measure of clinical pregnancy rate, live birth rate, or ovarian reserve was reported. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy rate, miscarriage rate, adverse pregnancy outcomes, and measures of ovarian reserve. Twelve articles involving 689 women were included in the systematic review. The intervention group underwent UAO at laparoscopic or abdominal myomectomy (UAO+M) (n = 470). The control group underwent myomectomy alone (n = 219). Seven articles involving 420 women were included in the meta-analysis (201 underwent UAO+M; 219 underwent myomectomy alone). Live births occurred in 54 of 201 (27%) women in the UAO+M group and in 74 of 219 (34%) women in the control group. Clinical pregnancies occurred in 73 of 201 (36%) women in the UAO+M group and in 102 of 219 (47%) control subjects. There was no difference in live birth rates (odds ratio 0.89; 95% CI 0.56-1.43; P = 0.51; 7 studies, 420 patients) or clinical pregnancy rates (odds ratio 0.81; 95% confidence interval 0.53-1.24; P = 0.33; 7 studies, 420 patients) between the UAO+M and control groups. Data on miscarriage rates, adverse pregnancy outcomes, and measures of ovarian reserve precluded meta-analysis. In conclusion, UAO at myomectomy is not associated with reductions in live birth or clinical pregnancy rates. Before routine use can be recommended in women desiring future fertility, more research is required on reproductive outcomes and effects on ovarian reserve. (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Sandhu, J. K., et al. (2021). "Oxidative Stress in Polycystic Ovarian Syndrome and the Effect of Antioxidant N-Acetylcysteine on Ovulation and Pregnancy Rate." Cureus 13(9): e17887.
	Polycystic ovarian syndrome (PCOS) is an endocrinological condition that leads to infertility in many females. N-acetylcysteine (NAC), a novel antioxidant, is being used as an adjuvant to treat infertility in females suffering from PCOS. This review aims to evaluate oxidative stress in females suffering from PCOS and assess whether the anti-oxidizing properties of NAC are beneficial in enhancing the rate of ovulation and pregnancy in infertile PCOS females. A literature search was conducted manually on PubMed and Google Scholar databases using the following keywords: "N-Acetylcysteine," "PCOS," "Oxidative stress," "Antioxidants," and "infertility" alone and/or in combination for data collection. The studies were manually screened and, after applying inclusion-exclusion criteria, 32 studies consisting of 2466 females of the reproductive age group are included in this review. Our review revealed that females suffering from PCOS tend to show elevated levels of inflammatory markers and a decrease in antioxidant capacity. When used in combination with clomiphene citrate or letrozole, NAC increases ovulation and pregnancy rate in infertile females suffering from PCOS and positively affects the quality of oocytes and number of follicles ≥18mm. Moreover, its side effect profile is low. It also results in a mild increase in endometrial thickness in some females. Future studies on a large sample size using NAC alone are highly recommended to evaluate its role as a single-drug therapy for treating infertility in females suffering from PCOS.

Sandzhieva, L. N., et al. (2022). "Personalized comprehensive rehabilitation program after surgical treatment of endometrial cancer: results of a prospective randomized comparative study." Obstetrics, Gynecology and Reproduction 16(2): 143-157.
	Aim: to evaluate effectiveness of a personalized comprehensive rehabilitation program in patients after surgical treatment of endometrial cancer (EC). Material and Methods. There were enrolled 61 patients of reproductive age (44.46 +/- 3.84 years) after radical treatment of endometrioid adenocarcinoma by stratifying subjects into 2 groups: group I - <> rehabilitation with a comprehensive program of restorative measures (n = 29), group II - < > rehabilitation with standard management of the postoperative period in accordance with volume and timeframe determined by clinical recommendations (n = 32). Quality of life (QoL) was determined using the following questionnaires: Functional Assessment of Cancer Therapy for Patients with Endometrial Cancer (FACT-En), Kupperman-Uvarova Modified Menopausal Index (MMI), The Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS). The program was based on four patient visits expected to occur at week 1 as well as 3, 6, 12 months after surgery, respectively. Results. In was found that 12 months post-surgery MMI in group I was decreased from 40.75 +/- 5.69 down to 26.45 +/- 4.84 score corresponding to mild postovariectomy syndrome (POES), whereas in group II - from 39.62 +/- 5.37 to 36.15 +/- 4.06 score estimated as moderate POES. In addition, at this time point patients in group I were noted to virtually fully recover sexual function assessed by FSFI (24.93 +/- 2.86 score), whereas in group II it was at markedly lower level (13.39 +/- 2.55 score; p < 0.001). According to the HADS, all subjects had level exceeding score of 11 at week 1 post-surgery corresponding to clinically significant anxiety and depression. Moreover, 6- and 12-months post-surgery subjects in group I lacked significant symptoms (score < 7 for each parameter), whereas in group II 12-month follow-up demonstrated subclinical level of anxiety and depression. According to the FACT-En, subjects in group I vs. group II revealed markedly higher QoL on visit 4 reaching 141.31 +/- 6.45 and 112.84 +/- 6.48 score, respectively. Conclusion. The <> personalized comprehensive rehabilitation program proposed here demonstrated high efficacy in EC patients after radical surgery compared to subjects underwent standard management in rehabilitation period. Use of the program during 12 months post-surgery allowed to minimize negative manifestations related to POES, positively impacted psycho-emotional status, significantly improved sexual function as well as QoL. Organizing comprehensive rehabilitation in post-surgical EC patients should be considered as one of high-priority approaches in public healthcare.Copyright © 2022 Vladikavkaz Mathematical Journal. All rights reserved.

Sankyo, D., et al. (2024). A Study of Raludotatug Deruxtecan (R-DXd) in Subjects With Platinum-resistant, High Grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer.
	No Results Available Drug: R-DXd|Drug: Gemcitabine|Drug: Paclitaxel|Drug: Topotecan|Drug: PLD Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment (Part A)|Progression-free Survival (PFS) Based on BICR Assessment (Part B)|Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment (Part B)|Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment|Duration of Response (DOR)|Progression-free Survival (PFS) Based on BICR and Investigator Assessment (Part A)|Disease Control Rate (DCR)|Overall Survival (OS)|Number of participants with Treatment-emergent Adverse Events (TEAEs)|Pharmacokinetic (PK) Analysis: Maximum Plasma Drug Concentration (Cmax) of R-DXd|Pharmacokinetic (PK) Analysis: Time to Reach Maximum Plasma Drug Concentration (Tmax) of R-DXP|Pharmacokinetic (PK) Analysis: Area Under the Concentration-Time Curve (AUC) of R-DXd|Pharmacokinetic (PK) Analysis: Terminal Half-Life (t1/2) of R-DXd|Percentage of Participants With Treatment Emergent Antidrug Antibody (ADA)|Percentage of Participants With Cancer Antigen 125 (CA-125) Response Rate|Cadherin-6 (CDH6) protein expression in tumor tissue as determined by immunochemistry assay and correlation with ORR, DoR, PFS and OS|Change in Score in the Quality of Life (QoL) Questionnaire|Time to Next Treatment (TTNT)|Progression-free Survival 2 (PFS2) Based on Investigator Assessment All Phase 2|Phase 3 650 Industry Allocation: Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment DS6000-109|REJOICE-Ovarian01|ENGOT-ov77|GOG-3096 December 31, 2029

Sansone, S., et al. (2022). "Role of Pessaries in the Treatment of Pelvic Organ Prolapse: A Systematic Review and Meta-analysis." Obstetrics and Gynecology 140(4): 613-622.
	Objective: To evaluate the existing evidence on the efficacy of pessaries in improving quality of life when used for the treatment of pelvic organ prolapse (POP).; Data Sources: We searched for the terms "pelvic organ prolapse" and "pessar/y/ies/ium or vaginal support device," and "safety or safe or outcome or complication or efficacy or effective or effectiveness" in PubMed, EMBASE, and CINAHL on March 16, 2020. A search was also performed on ClinicalTrials.gov , with no studies fitting our strict inclusion and exclusion criteria.; Methods of Study Selection: Studies that reported pretreatment and posttreatment mean scores and SDs after pessary treatment for standardized questionnaires were included. Studies performed in pediatric populations, pregnancy, and use of pessaries not for prolapse were excluded. Three reviewers independently screened studies.; Tabulation, Integration, and Results: Data abstraction was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data were pooled for meta-analysis when reported by at least three studies. The primary study outcome was change in mean pretreatment and posttreatment questionnaire scores, which included those for the PFDI-20 (Pelvic Floor Distress Inventory- Short Form 20), PFIQ-7 (Pelvic Floor Impact Questionnaire - Short Form 7), and subscale POPIQ (Pelvic Organ Prolapse Impact Questionnaire Long Form). A random-effects model was used to combine estimates and capture between-study heterogeneity using the I 2 -statistic. Eight studies including 627 patients were included for systematic review. The mean (SD) age was 63.0±12.2 years, and the majority of patients had stage III prolapse (48.1%) followed by stage II prolapse (43.2%) when reported. Although variable, the majority of studies conducted 3-month follow-up. A negative change in pretreatment and posttreatment scores was noted, signifying improvement after pessary use: PFDI-20 mean change -46.1 (95% CI -65.4 to -26.8); PFIQ-7 mean change -36.0 (95% CI -46.0 to -26.0); POPIQ-7 (Pelvic Organ Prolapse Impact Questionnaire-7) mean change -16.3 (95% CI -26.8 to -5.7). No significant heterogeneity was found.; Conclusion: Based on improvements in standardized questionnaire scores, pessaries are effective treatment options for POP.; Systematic Review Registration: PROSPERO, CRD42020172618.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Santerre-Baillargeon, M., et al. (2023). "Mediators of change in cognitive-behavioral couple therapy for genito-pelvic pain: Results of a randomized clinical trial." Health psychology : official journal of the Division of Health Psychology, American Psychological Association 42(3): 161-171.
	Objective: A novel cognitive-behavioral couple therapy (CBCT) has shown efficacy for treating provoked vestibulodynia (PVD), the most common type of genito-pelvic pain, in comparison to topical lidocaine. However, mechanisms of therapeutic change have not been determined. We examined women's and partners' pain self-efficacy and pain catastrophizing as mediators of change in CBCT, using topical lidocaine as a control group.; Method: 108 couples coping with PVD were randomized to 12-week CBCT or topical lidocaine and assessed at pre-treatment, post-treatment, and six-month follow-up. Dyadic mediation analyses were conducted.; Results: CBCT was not more effective in increasing pain self-efficacy than topical lidocaine, so this mediator was discarded. In women, decreases in pain catastrophizing at post-treatment mediated improvement in pain intensity, sexual distress, and sexual function. In partners, decreases in pain catastrophizing at post-treatment mediated improvement in sexual function. Partners' decreases in pain catastrophizing also mediated reductions in women's sexual distress.; Conclusions: Pain catastrophizing may be a mediator specific to CBCT for PVD, explaining improvements in pain and sexuality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Santhosh, S. B., et al. (2019). "Ovarian solid tumors: Current treatment and recent developments using stimuli-responsive polymers: A systemic review." Journal of Drug Delivery Science and Technology 51: 621-628.
	Among gynaecologic malignancies, ovarian cancer is the sixth most common cancer leading to death worldwide. Current treatment based on epigenetic strategies use histone deacetylase (HDAC) and DNA methyl tranferase (DNMT) inhibitors have several shortcomings. Further research to develop better inhibitors were terminated due to undesirable toxicity and insignificant results. In recent years researchers have, therefore, shown interest in drug delivery systems (DDS) to enhance the effectiveness of anticancer drugs for ovarian solid tumors. In this context stimuli-responsive polymers, namely temperature, pH, enzyme, light, etc., have shown considerable potential. These polymeric-drug conjugates can extend the circulation half-life of the drugs, decrease the rate of clearance of the drug and its non-specific absorption into the systemic tissues and specifically target tumor tissues passively by the enhanced permeability and retention (EPR) effect and the application of mild hyperthermia. In the present report, to the best of our knowledge we are the first one who review the novel approaches that have been made in the stimuli-responsive polymeric drug delivery systems for the targeted delivery of anticancer drugs to ovarian solid tumors.Copyright © 2019 Elsevier B.V.

Santoni, M., et al. (2019). "Targeted therapy for solid tumors and risk of hypertension: a meta-analysis of 68077 patients from 93 phase III studies." Expert review of cardiovascular therapy 17(12): 917-927.
	Objective : Hypertension is a common adverse event with targeted agents in cancer patients and can lead to serious and sometimes lethal cardiovascular complications. The authors performed a meta-analysis of clinical trials aiming to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade Hypertension Events (HE) in patients with solid tumors receiving targeted therapy. Methods : A review of citations from PubMed was performed and studies were selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was limited to randomized phase III trials published in English focused on the efficacy and safety of targeted agents in cancer patients, reporting data on HE. Incidence, RR and relative 95% CIs were analyzed using random or fixed-effects models. Overall incidences were calculated and further compared with the chi-squared test for proportions. Results : Ninety-three phase III trials were included, with a total of 68,077 patients. Prostate cancer was the most represented (18.9%), followed by breast cancer (17.3%) and colorectal cancer (16.4%). The incidence of all- and high-grade HE was 23.47% and 8.57%, respectively, with the highest incidence of serious HE reported by adjuvant Sunitib/Sorafenib (29.03%). The highest RR of high-grade HE was observed with Bevacizumab in patients with advanced cervical cancer. By drug category, the highest RR of high-grade HE was reported by VEGFR/EGFR TKIs. Conclusion : According to these data, monitoring this class of toxicities is of primary importance to avoid hypertension worsening and, thus, the risk of major cardiovascular events.

Santoro Anna, M., et al. (2022). "Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study." Menopause (New York, N.Y.) 29(10): 1200-1203.
	Objective: The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women.; Methods: Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month.; Results: There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment.; Conclusions: Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.; Competing Interests: Financial disclosure/conflicts of interest: None reported. (Copyright © 2022 by The North American Menopause Society.)

Santoro, N., et al. (2023). "Fezolinetant Treatment of Moderate-to-Severe Vasomotor Symptoms Associated with Menopause: Effect of Intrinsic and Extrinsic Factors in Two Phase 3 Studies." Obstetrics and Gynecology 141(5 Supplement 1): 12S.
	INTRODUCTION: Fezolinetant was well tolerated and effective in reducing the frequency and severity of menopause-associated, moderate-to-severe vasomotor symptoms (VMSs) in SKYLIGHT 1 and 2. This analysis investigated the relationship between intrinsic (individual-related) and extrinsic (outside-influence) factors and fezolinetant efficacy. METHOD(S): In these phase 3, double-blind, placebo-controlled, IRB-approved studies (NCT04003155 and NCT04003142), women aged 40 through 65 years with moderate-to-severe VMSs (seven or more hot flushes/day) were randomized to once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. For this pooled analysis, the influence of intrinsic and extrinsic factors on change from baseline to week 12 in the frequency of moderate-to-severe VMSs was assessed by subgroups using a mixed model for repeated measurement. RESULT(S): One thousand twenty-two women took one or more dose (placebo, n5342; fezolinetant 30 mg, n5339; fezolinetant 45 mg, n5341). Consistent improvements in VMS frequency over placebo were observed across subgroups with fezolinetant 45 mg. For intrinsic factors, least-square mean differences (95% CI) between fezolinetant 45 mg and placebo were as follows: age less than 55 years, 22.78 (23.74, 21.82); 55 years or older, 22.24 (23.23, 21.24); White race, 22.17 (22.93, 21.41); Black race, 23.67 (25.32, 22.01); and body mass index of 30 kg/m2 or higher, 22.87 (24.11, 21.63). Extrinsic factors showed the following differences: current smoker, 23.48 (25.19, 21.77); former/never smoker, 22.32 (23.08, 21.57); European resident, 21.50 (22.73, 20.26); and North American resident, 22.95 (23.78, 22.13). Similar efficacy trends were observed with fezolinetant 30 mg. CONCLUSION(S): Fezolinetant was efficacious in treating moderate-to-severe VMSs associated with menopause across the intrinsic and extrinsic factors investigated, demonstrating its potential utility in a broad population.

Santoro, N., et al. (2024). "Effect of fezolinetant on moderate-to-severe vasomotor symptoms in subgroups based on hormone therapy history: pooled data from two randomized phase 3 studies." Journal of Neurosurgical Anesthesiology 36(1): 1259.
	Objective: Two phase 3 studies (SKYLIGHT 1 and 2; NCT04003155 and NCT04003142) demonstrated the efficacy, safety, and tolerability of fezolinetant treatment for vasomotor symptoms (VMS) due to menopause. As a nonhormonal agent, fezolinetant may be a potential therapeutic alternative for those unable or unwilling to take hormone therapy (HT). Additional analyses using pooled data from SKYLIGHT 1 and 2 assessed fezolinetant efficacy in participant subgroups who were considered potentially unsuitable for HT. Design(s): SKYLIGHT 1 and 2 had the same design. Both were double-blind, placebo-controlled studies of once-daily placebo, fezolinetant 30 mg or 45 mg for 12 weeks in women >=40-<65 y with moderate-to-severe VMS (minimum average >=7 hot flashes/day). HT history subgroups were mutually exclusive and categorized using the following hierarchy: contraindicated; caution; stopped for medical concerns; averse; naive/willing. Subgroup assignments were based on participant answers to the HT questionnaire that was completed as part of the electronic case report form at baseline. Result(s): A total of 1022 participants took >=1 dose of study medication and comprised the pooled group (placebo, n=342; fezolinetant 30 mg, n=339; fezolinetant 45 mg, n=341). Irrespective of HT history, there was an improvement in the frequency of moderateto- severe VMS from baseline to weeks 4 and 12 (Table) in both fezolinetant groups compared with placebo. Improvement is indicated by a least squares mean difference of <0 for fezolinetant vs placebo. Similarly, there was an improvement across all HT history subgroups in the severity of moderate-to-severe VMS from baseline to weeks 4 and 12 in both fezolinetant groups compared with placebo. In the subgroup who were HT unsuitable (including averse), treatment-emergent adverse events (TEAEs) occurred in 41.3% (121/293) of the placebo group, 40.8% (118/289) of the fezolinetant 30 mg and 39.4% (112/284) of the fezolinetant 45 mg groups. The most frequent TEAE was headache (5.5% placebo; 4.2% fezolinetant 30 mg; 5.6% fezolinetant 45 mg). There was 1 drug-related serious TEAE (transaminases increased) in the fezolinetant 30 mg group. Conclusion(s): This pooled analysis from SKYLIGHT 1 and SKYLIGHT 2 demonstrates the efficacy of fezolinetant in reducing the frequency and severity of VMS due to menopause compared with placebo in participants considered unsuitable for or unwilling to take HT. The findings are consistent with the effect observed in the overall participant population. In addition, fezolinetant was well tolerated in the HT unsuitable (including averse) subgroup. (Table Presented).

Santos, A. C., et al. (2024). "Effectiveness of group aerobic and/or resistance exercise programs associated with pelvic floor muscle training during prenatal care for the prevention and treatment of urinary incontinence: A systematic review." Neurourology and Urodynamics 43(1): 205-218.
	Aim: To evaluate the effectiveness of aerobic and/or resistance group exercise programs associated with pelvic floor muscle training (PFMT) during prenatal care for the prevention and treatment of urinary incontinence (UI) using the best level of evidence. Method(s): A search was carried out in the MEDLINE/PubMed, LILACS, PEDro, CENTRAL, and SCOPUS databases, without restrictions. The terms "urinary incontinence" and "pregnant woman" were used. Randomized and quasi-randomized clinical trials were included using aerobic and/or resistance exercise programs plus PFMT as an intervention compared to usual care. The Cochrane tool (RoB 2.0) and GRADE were used to assess risk of bias and certainty of evidence, respectively. Quantitative analysis was assessed by meta-analyses. Result(s): Five publications were included. There was a reduction in the reports of UI postintervention at 16 weeks (RR: 0.83; 95% CI: 0.74-0.93, one study, 762 women, random effects: p = 0.002) and after 3 months (RR: 0.76; 95% CI: 0.60-0.95, one study, 722 women, random effects: p = 0.02), based on moderate certainty of evidence and improvement in UI-specific quality of life (MD: -2.42; 95% CI: -3.32 to -1.52, one study, 151 women, random effects: p < 0.00001), based on low quality of evidence. Other results showed no difference between the postintervention groups, with low and very low evidence. Conclusion(s): There is moderate evidence that the aerobic and/or resistance exercise program associated with PFMT compared to usual care can reduce postintervention UI, as well as 3 months postintervention, and that it can improve UI-specific quality of life, but with low-evidence certainty.Copyright © 2023 Wiley Periodicals LLC.

Santos, H., et al. (2022). "URODYNAMIC PROFILE OF VOIDING IN PELVIC ORGAN PROLAPSE PATIENTS AFTER SURGERY: A SYSTEMATIC REVIEW WITH META-ANALYSIS." Journal of urology 207(SUPPL 5): e711-e712.
	INTRODUCTION AND OBJECTIVE: Pelvic organ prolapse (POP) originates due to defects on the female pelvic floor and is a prevalent disorder in women. Stress urinary incontinence (SUI), urge urinary incontinence (UUI), and obstructive symptoms may concur in these patients. Surgical treatment of POP aims to restore the anatomy and function of the genitals; however, it may prompt urinary symptoms not presented previously. We aimed to perform a systematic review and meta-analysis of urodynamic changes in patients undergoing surgical correction for POP. METHOD(S): This study was conducted according to the PRISMA protocol. Studies in English, published from 1976 to July 2020 in Pubmed and Cochrane were included. Studies included contained data from urodynamic evaluation from before and after vaginal surgery for POP, with or without anti-incontinence procedures. The main urodynamic data collected were: (1) Free uroflowmetry: Qmax, voided volume, and PVR; (2) Cystometry: Bladder capacity, presence of DO, SUI or UUI and VLPP; (3) Pressure x flow study: PdetQmax, Qmax and PVR. Bias risk assessment was performed in all studies. RESULT(S): 22 studies published between 1989 and 2018 were included, involving 1,549 women. MUS placement was assessed independently in 3 studies. Patients had a significantly higher prevalence of DO before surgery (OR 1.56, 95% CI 1.06-2.29; p=0.02), surgeries without sling placement demonstrated a tendency of ameliorating DO. Patients that did not receive sling were more incontinent after surgery, with a lower prevalence of SUI before surgery (OR 0.23, 95% CI 0.09-0.61; p=0.003). Bladder emptying parameters improved after surgery, with higher PdetQmax before surgery (IV 3.23, 95% CI 0.45- 1.18; p=0.02). For patients that did not receive MUS, a lower Qmax (IV -3.19, 95% CI -4.09 - -2.30; p=<0.001) and a higher PVR (IV 27.89, 95% CI 15.68-40.1; p<0,001) was observed before surgery. CONCLUSION(S): POP correction surgery yields better urodynamic emptying parameters, with a lower PdetQmax, higher Qmax and lower PVR. The procedure is associated with a reduction of detrusor overactivity. Sling placement enhances obstructive parameters. Patients significantly improve their symptoms with POP correction surgery.

Santos Isis Kelly, D., et al. (2021). "Effect of high-intensity interval training on metabolic parameters in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials." PloS One 16(1): e0245023.
	Background: Our aim was to assess the effect of high-intensity interval training (HIIT) on metabolic parameters and body composition in women with polycystic ovary syndrome (PCOS).; Methods and Analysis: A systematic review and meta-analysis of randomized controlled trials was conducted using Embase, MEDLINE (via Ovid), PubMed, Sport Discus, Scopus, Web of Science, Cochrane Library and Google Scholar (advanced feature) up to September 2020. Two authors independently screened citations and determined the risk of bias and quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted using random effects model.; Results: Seven trials (n = 423) were included in the systematic review. The studies included HIIT interventions vs. moderate exercise or control groups. Most studies were small (average 32, range 24-110 participants) and of relatively short duration (10-16 weeks). The training intensity was performed between 90% and 95% of the maximum heart rate, three times a week, for at least 10 weeks. Insulin resistance, measured using homeostatic model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) showed a significant decrease (MD -0.57; 95% CI, -0.98 to -0.16, p = 0.01), (MD -1.90, 95% CI -3.37, -0.42, p = 0.01) with moderate and high certainty of evidence, respectively.; Conclusion: Results support that HIIT alone is effective for reducing HOMA-IR and BMI in women with PCOS. However, evidence is limited to discern the effect of HIIT on other outcomes. Future studies with a longer duration (> 16 weeks), larger sample sizes and other outcomes are needed.; Competing Interests: The authors have declared that no competing interests exist.

Santos, S., et al. (2022). "Educational Programs and Sexual Counselling for Postmenopausal Sexual Dysfunction: A Systematic Review and Meta-Analysis." The Journal of Sexual Medicine 19(1): 54-63.
	Background: Female sexual dysfunction has a high prevalence in women in the postmenopausal period. Not only factors like comorbidities and chronic illnesses are responsible for this high prevalence, but also psychological and interpersonal factors play a significant role. Sexual counselling educational programs have shown positive sexual behavioral changes and they should be considered the first line approach to female sexual dysfunction in this group of women.; Aim: To review the evidence of the efficacy of sexual counselling educational programs for sexual dysfunction in postmenopausal women.; Methods: A systematic search was performed in February 2021 from electronic databases (MEDLINE, CENTRAL, and Scopus), unpublished studies, ongoing clinical trials, conference abstracts and journal archives, dissertations and theses, gray literature and free search on the Google Scholar search engine. Studies that evaluate the effectiveness of sexual educational programs in postmenopausal women were selected. Study selection and data extraction were performed by 2 independent researchers. Extracted data included author identification, publication date, geographic location, study population and sample size, type of intervention, sexual function evaluation tool and outcome. Studies that evaluate sexual function by using the Female Sexual Function Index (FSFI) were included in the meta-analysis, calculating the mean difference.; Outcomes: Improvement of sexual function in postmenopausal women.; Results: We included 8 studies in the systematic review, 6 randomized and 2 nonrandomized controlled trials, with a total sample size of 619 women, aged between 39 and 75 years old, all in menopause for less than 5 years. The studies described sexual education programs, with 4-10 sessions, 45-60 minutes each, including themes like sexual anatomy, physiological sexual response, menopause, methods of stimulation, and common sexual myths. Five studies also included cognitive-behavior therapy and 3 studies assessed mindfulness techniques. Six studies evaluated the effectiveness of sexual educational programs using FSFI. The results showed that sexual counselling educational programs had statistically significant effects on enhancing the total FSFI score (mean difference = +7.14, 95% confidence interval = 3.70-10.6, P < .0001) in comparison to routine care. Results were also significant in all evaluated sex domains: pain, arousal, lubrication, desire, orgasm and satisfaction (P < .05).; Conclusion: Our meta-analysis shows that sexual counselling educational programs are effective in improving sexual dysfunction in postmenopausal women when compared to routine care. These are simple approaches, easily administered with minimal resources that help prevent the psychological and social consequences of sexual dysfunction at this age. IMS Silva, MP Pinto, D Gonçalves. Educational Programs and Sexual Counselling for Postmenopausal Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:54-63. (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Sapienza Lucas, G., et al. (2019). "Detection of air gaps around the cylinder by postinsertion computed tomography in vaginal cuff brachytherapy: A prospective series, systematic review, and meta-analysis." Brachytherapy 18(5): 620-626.
	Purpose: Postinsertion computed tomography (CT) can identify air gaps (AGs) around the cylinder in vaginal cuff brachytherapy (VCB). This study investigates the incidence and location of AGs.; Methods and Materials: Planning CTs of 22 prospectively recruited patients (NCT02091050) treated with 2.6 cm (n = 8) and 3.0 cm (n = 14) cylinders were evaluated. In addition, a systematic literature review and meta-analysis was performed (PubMed and EMBASE). The pooled incidence of AGs was calculated by using the random-effects model weighted by inverse variance.; Results: In 18 cases (82%), a total of 45 AGs were found: 26 within the 2 cm cranial length and 19 between 2 and 4 cm of the cylinder. The mean AG diameter was 3.7 mm (range: 1.3-11.8). Cylinder diameter, primary tumor site, and use of external beam radiotherapy were not associated with AG incidence. Systematic literature review revealed nine additional relevant studies, totaling 657 patients. The pooled incidence of patients with ≥1 AG was 67% (95% confidence interval: 50-83). AGs were located at the apex in 43.4%-94.4% of cases. In patients with ≥1 AG (n = 244), the pooled mean number of AGs was 2.18 per patient. The mean dose reduction varied from 9.6% to 29.3%.; Conclusion: More than two-thirds of VCB cases present with AGs, which are most commonly at the apex and can potentially reduce mucosal dose. By identifying AGs, postinsertion CT can facilitate selection of optimal cylinder size in VCB. (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Sapienza Lucas, G., et al. (2020). "Pelvic Insufficiency Fractures After External Beam Radiation Therapy for Gynecologic Cancers: A Meta-analysis and Meta-regression of 3929 Patients." International Journal of Radiation Oncology, Biology, Physics 106(3): 475-484.
	Purpose: To estimate the overall rate, symptomatic proportion, and most common sites of pelvic insufficiency fracture (PIF) after external beam radiation therapy for gynecologic cancers based on posttreatment computed tomography, magnetic resonance imaging, positron emission tomography, or bone scintigraphy.; Methods and Materials: A systematic search of databases (PubMed and EMBASE) was performed (CRD42019125679). The pooled summary of overall PIF and the proportion of symptomatic cases were calculated using the random-effects model weighted by the inverse variance. A multivariate meta-regression was performed to evaluate potential sources of heterogeneity regarding PIF fractures.; Results: Twenty-one studies met the inclusion criteria (total 3929 patients). Five hundred four patients developed PIF, translating to an overall rate of 14% (95% confidence interval, 10%-18%, based on 21 studies). Among these cases with PIF, the proportion of symptomatic patients was 61% (95% confidence interval, 52%-69%, based on 14 studies). The total number of PIFs was 704 (mean, 1.72 PIFs per each patient to develop PIF, based on 14 studies). More recent series (P = .0074) and the use of intensity modulated radiation therapy (P = .0299) were associated with lower fracture rates. The most common fracture sites were sacroiliac joint (39.7%), body of the sacrum (33.9%), pubis (13%), lumbar vertebra (7%), iliac bone (2.8%), acetabulum (2.1%), and femoral head/neck (1.5%). The median time to fracture was 7.1 to 19 months after radiation therapy.; Conclusions: The incidence of PIF after radiation therapy for gynecologic cancers is high (14%), with the majority affecting the sacral bone or joint (73.6%), although this risk appears to be lower with intensity modulated radiation therapy. Posttreatment bone surveillance is warranted in this population because nearly 40% of patients were asymptomatic at the time of PIF diagnosis. (Copyright © 2019 Elsevier Inc. All rights reserved.)

Sapouna, V., et al. (2023). "Pelvic Floor Muscle Training and Its Benefits for Multiple Sclerosis Patients Suffering From Urinary Incontinence and Sexual Dysfunction." Cureus 15(10): e47086.
	Several reports have been published during the last decade studying the effect of pelvic floor muscle training (PFMT) in treating urinary incontinence and sexual dysfunction in multiple sclerosis (MS) patients. The aim of the current study is to bring up-to-date findings of earlier systematic reviews, taking into account data published up till June 2023. Databases such as PubMed, Scopus, and EBSCOhost were screened for randomized controlled studies, clinical trials, and systematic reviews. The keywords for the current review were MS, urinary incontinence, sexual function, and PFMT. The implementation of predetermined eligibility criteria permitted an appropriate and convenient study selection. English language publications alone were considered. After removing duplicates and screening the initially recovered articles, an initial search within the present review identified 19 studies. Finally, 10 randomized control trials and two systematic reviews were eligible for evaluation and included in the current review. The outcome measures were the severity of incontinence or overactive bladder, leakage episodes, sexual dysfunction, health-related quality of life, and adherence to PFMT. PFMT is a convenient and effective treatment tool that can significantly improve health-related quality of life and reduce the severity of urinary incontinence and overactive bladder symptoms in people with MS. The present review confirms the effectiveness of specific exercises on leakage episodes, pad usage, sexual dysfunction, compliance to treatment, and treatment satisfaction. Further research is needed to strengthen the reported results.

Sappenfield, E. C., et al. (2021). "The impact of preoperative pelvic pain on outcomes after vaginal reconstructive surgery." American Journal of Obstetrics and Gynecology 225(5): 564.e561-564.e569.
	BACKGROUND: Pelvic pain is a debilitating condition that is common among women with pelvic floor disorders. Limited information is known about the impact of preoperative pelvic pain on outcomes after vaginal reconstructive surgery. OBJECTIVE: This study aimed to compare the outcomes after vaginal reconstructive surgery between women with and without preoperative pelvic pain. STUDY DESIGN: Baseline and postoperative data were analyzed from the "Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial." The multicenter trial involved women with anterior prolapse without symptoms of stress incontinence randomized to receive either a midurethral sling or sham incisions during a vaginal reconstructive surgery. Participants completed the visual analog scale adapted for suprapubic pain and Pelvic Floor Distress Inventory at baseline, 3 months, and 12 months. Preoperative pelvic pain was defined as a response of "5" or greater on pain on the visual analog scale or answering "moderately" or "quite a bit" on the Pelvic Floor Distress Inventory question, "Do you usually experience pain in the lower abdomen or genital area?" Outcomes and complication rates were compared between women with and without pelvic pain. RESULTS: The "Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial" participants included 112 women with pelvic pain (58 had a midurethral sling and 54 had sham incisions) and 212 women without pelvic pain (105 had a midurethral sling and 107 had sham incisions). Women who had a midurethral sling and pelvic pain were younger than women without pelvic pain (60.3±12.1 vs 65.1±8.6; P=.004). Women who had sham incisions and pelvic pain were more likely of Hispanic ethnicity than women without pelvic pain (27.8% vs 9.4%; P=.002). Patient improvement based on the Patient Global Impression of Improvement scale did not differ between arms. Women with pelvic pain had greater improvement on the visual analog scale pain scores after a surgical procedure at 3 months (-3.1±2.9 vs -0.4±1.6; P<.001) and at 12 months (-3.4±3.0 vs -0.6±1.6; P<.001) than women without pain, although their pain scores remained higher than those without preoperative pelvic pain at all time points (P<.001 for all). Similar improvements were found on the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire. The differences observed were not affected by whether women were in the midurethral sling or sham arm of the trial. Postoperative urinary tract infection and incomplete bladder emptying did not differ between the groups. CONCLUSION: Women with preoperative pelvic pain experienced significant improvements in pain and pelvic floor symptoms with vaginal reconstructive surgery and had similar subjective improvement postoperatively compared with women without preoperative pelvic pain. Reassuringly, the performance of a midurethral sling did not have an impact on the results.

Sarah, B., et al. (2021). "The effect of mindfulness-based interventions on perinatal and postnatal depression and anxiety: A systematic review."
	
Sarah, C., et al. (2021). "Endovascular Treatment for Pelvic Congestive Syndrome Embolization and Its Impact in Chronic Pelvic Pain Resolution: A Systematic Review and Metanalysis."
	
Sarah, S., et al. (2021). "Methotrexate versus expectant management for treatment of tubal ectopic pregnancy: protocol for an individual patient data meta-analysis."
	
Sarentha, C., et al. (2021). "The Effectiveness of the Use of Progestins in the Symptomatic Management of Endometriosis."
	
Sarfraz, Z., et al. (2024). "Evaluating cognitive behavioral therapy as a solution for postnatal depression in economically disadvantaged regions." Archives of Women's Mental Health.
	Purpose: Postnatal depression (PND) impacts numerous women after childbirth, leading to various impairments in their lives. Mental health interventions, such as cognitive behavioral therapy (CBT), need further evaluation in low- and middle-income countries (LMICs) where resources may be scarce. This study aimed to assess the effectiveness of CBT in treating PND in women from LMICs, comparing it to standard care. Method(s): A systematic review and meta-analysis were conducted following the PRISMA Statement 2020 guidelines. Databases such as PubMed, CINAHL Plus, Cochrane Library, and PsycINFO were searched until September 2022. A modified Delphi process was employed to identify relevant studies. The primary outcome was mean depression scores, measured by the Edinburgh postnatal depression scale at baseline and post-intervention. Result(s): Out of 487 studies identified, five trials were included, totaling 1056 participants (520 in the intervention group and 536 in the comparator group). At baseline, a minor, insignificant positive effect size was found (Cohen's d = 0.1, 95% CI = - 0.15, 0.35). Post-CBT, the intervention group showed significant improvements in depression scores (Cohen's d = - 1.9, 95% CI = - 3.8, 0). When accounting for the influence of one study, (Ngai et al., Psychother Psychosom 84:294-303, 2015), which held substantial weight in the initial analysis, the effect size was adjusted to d = 0.5, highlighting a lesser but still significant difference. Conclusion(s): CBT appears to be effective in improving PND symptoms among women in LMICs and may be considered a first-line treatment for at-risk mothers, including those who are displaced. However, the significant impact of one study on the results emphasizes the need for more rigorous research. The study also highlights the challenges and limitations of providing psychotherapies across LMICs, emphasizing the need for culturally adapted and contextually appropriate interventions to ensure successful implementation and sustainability of mental health care for postnatal women in these settings.Copyright © 2024, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Sarkar, A., et al. (2023). "Comparison of Outcomes following Vaginal Natural Orifice Transluminal Endoscopic Surgery and Laparoendoscopic Single-site Surgery in Benign Hysterectomy: A Systematic Review and Meta-analysis." Gynecology and Minimally Invasive Therapy 12(4): 195-202.
	Gradually increasing interest in laparoscopic surgeries has led to the advent of various lesser invasive techniques in the form of vaginal natural orifice transluminal endoscopic surgery (vNOTES) and laparoendoscopic single-site (LESS) surgery. Very few studies have analyzed the advantages and disadvantages of vNOTES over LESS surgeries in hysterectomy. After a comprehensive search, full texts of relevant manuscripts were obtained to assess eligibility for recruitment. A comprehensive meta-analysis was subsequently performed to compare the outcomes of vNOTES and LESS in hysterectomy, and forest plots were constructed. Four articles were rendered for review (three retrospective cohort studies and one randomized controlled trial). Three studies showed lesser postoperative pain in vNOTES compared to LESS. In one study, postoperative vaginal pain was higher in vNOTES due to additional suture between uterine artery and vaginal wall. The meta-analysis concluded that vNOTES could be better alternative to LESS hysterectomies. However, further large multicentric randomized trials are required for the standardization of the surgical method.Copyright © 2023 Gynecology and Minimally Invasive Therapy.

Sarmento, A. L. C., et al. (2022). "Perspectives on the Therapeutic Effects of Pelvic Floor Electrical Stimulation: A Systematic Review." International Journal of Environmental Research and Public Health 19(21): 14035.
	Pelvic, perineal, and nervous lesions, which derive principally from pregnancy and childbirth, may lead to pelvic floor dysfunctions, such as organ prolapses and lesions in the nerves and muscles due to muscle expansion and physiology. It is estimated that 70% of women affected by this clinical picture have symptoms that do not respond to the classical treatments with antimuscarinic and anticholinergic drugs. Therefore, resorting to efficient alternatives and less invasive methods is necessary to assist this public health problem that predominantly affects the female population, which is more susceptible to the risk factors. This study aimed to perform an updated and comprehensive literature review focused on the effects of pelvic floor electrical stimulation, considering new perspectives such as a correlation between electric current and site of intervention and other molecular aspects, different from the present reviews that predominantly evaluate urodynamic aspects. For that purpose, PubMed and ScienceDirect databases were used to perform the search, and the Methodi ordinatio method was applied. With well-researched therapeutic effects, electrical stimulation induced promising results in histological, nervous, and molecular evaluations and spinal processes, which showed beneficial results and revealed new perspectives on ways to evoke responses in the lower urinary tract in a non-invasive way. Thus, it is possible to conclude that this type of intervention may be a non-invasive alternative to treat pelvic and perineal dysfunctions.Copyright © 2022 by the authors.

Sarmento Ayane, C. A., et al. (2021). "Physical methods for the treatment of genitourinary syndrome of menopause: A systematic review." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 153(2): 200-219.
	Background: Genitourinary syndrome of menopause (GSM) negatively affects sexual function and quality of life. Techniques like laser and radiofrequency are being used to manage GSM, particularly in women with contraindications for hormone therapy.; Objectives: To verify whether the physical methods of laser and radiofrequency can be recommended as safe and effective options for the treatment of GSM/urinary urgency or incontinence in pre- and postmenopausal women.; Search Strategy: Databases were comprehensively searched using combinations of the following keywords in any language: "postmenopause"; "genitourinary syndrome of menopause"; "vaginal atrophy"; "radiofrequency"; and "laser."; Selection Criteria: Full articles of case-control, cross-sectional, cohort, randomized clinical trials, and quasi-randomized or controlled clinical trials were included.; Data Collection and Analysis: All authors independently evaluated the design of the studies for quality of reporting, risk of bias, and quality of evidence.; Main Results: Of the included 49 studies, 37 were on the CO 2 laser, 10 on the Erbium laser, and two on radiofrequency.; Conclusions: Laser and radiofrequency therapy could be promising and safe therapeutic options for GSM/urinary incontinence. However, the study findings cannot be generalized until new randomized clinical trials are performed that confirm the strength of the evidence. This review has been registered with PROSPERO: CRD42020141913. (© 2020 International Federation of Gynecology and Obstetrics.)

Sarmento Ayane Cristine, A., et al. (2022). "Efficacy of Hormonal and Nonhormonal Approaches to Vaginal Atrophy and Sexual Dysfunctions in Postmenopausal Women: A Systematic Review." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 44(10): 986-994.
	Objective: To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women.; Data Sources: We conducted a search on the PubMed, Embase, Scopus, Web of Science, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, as well as on clinical trial databases. We analyzed studies published between 1996 and May 30, 2020. No language restrictions were applied.; Selection of Studies: We selected randomized clinical trials that evaluated the treatment of sexual dysfunction in postmenopausal women.; Data Collection: Three authors (ACAS, APFC, and JL) reviewed each article based on its title and abstract. Relevant data were subsequently taken from the full-text article. Any discrepancies during the review were resolved by consensus between all the listed authors.; Data Synthesis: A total of 55 studies were included in the systematic review. The approaches tested to treat sexual dysfunction were as follows: lubricants and moisturizers (18 studies); phytoestrogens (14 studies); dehydroepiandrosterone (DHEA; 8 studies); ospemifene (5 studies); vaginal testosterone (4 studies); pelvic floor muscle exercises (2 studies); oxytocin (2 studies); vaginal CO 2 laser (2 studies); lidocaine (1 study); and vitamin E vaginal suppository (1 study).; Conclusion: We identified literature that lacks coherence in terms of the proposed treatments and selected outcome measures. Despite the great diversity in treatment modalities and outcome measures, the present systematic review can shed light on potential targets for the treatment, which is deemed necessary for sexual dysfunction, assuming that most randomized trials were evaluated with a low risk of bias according to the Cochrane Collaboration risk of bias tool. The present review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100488).; Competing Interests: The authors have no conflict of interests to declare. (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Sarrazin, C., et al. (2022). "Synthetic mid-urethral slings for the treatment of stress urinary incontinence in women with neurogenic lower urinary tract dysfunction: a systematic review." International Urogynecology Journal 33(4): 767-776.
	Introduction and hypothesis: The aim of our study was to evaluate the efficiency and safety of synthetic mid-urethral slings (sMUS) for the treatment of stress urinary incontinence (SUI) in women with neurogenic lower urinary tract dysfunction (NLUTD). Method(s): A systematic review was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MEDLINE, Embase and Cochrane controlled trials databases were systematically searched from January 1995 to April 2021. Studies including adult women with NLUTD who had a sMUS for SUI were considered for inclusion. Primary outcome was success of the surgery according to study criteria. Secondary outcomes were complications, especially de novo urgency, urinary retention, tape exposure and revision for complications. Result(s): A total of 752 abstracts were screened and 9 studies were included, representing 298 patients. The mean age was 52 years and median follow-up was 41.3 months. sMUS insertion was successful in 237 patients (79.5%). The median rate of de novo urgency was 15.7% (range 8.3-30%). In patients with spontaneous voiding, the median rate of retention was 19.3% (range 0-46.7%) and 21 out of 26 patients required intermittent self-catheterisation. Four cases of tape exposure were reported, and 8 patients underwent a revision for complications. Conclusion(s): This review suggests that sMUS might offer interesting success rates and acceptable morbidity and could be considered for the treatment of SUI in women with NLUTD. Further studies are required to define which patients would be more likely to benefit from this intervention, as well as its place among the other surgical treatments for SUI.Copyright © 2021, The International Urogynecological Association.

Sascha, S., et al. (2021). "Risk factors for primary pelvic organ prolapse and recurrence after surgical correction: an updated systematic review."
	
Sassani, J. C., et al. (2023). "Cost-Utility Analysis of Midurethral Sling Timing among Women Undergoing Prolapse Surgery." Obstetrical and Gynecological Survey 78(11): 642-643.
	Approximately 25% of women in the United States are affected by pelvic floor disorders, with estimates pointing to a 50% increase in urinary incontinence prevalence and pelvic organ prolapse (POP) by 2050. Surgery for stress urinary incontinence (SUI) is also often required, which adds to economic burdens of pelvic floor disorders. Determining the POP patients who would benefit most from concomitant midurethral slings (MUSs) remains a clinical challenge. Performing a concomitant MUS procedure with a prolapse surgery is currently determined by variables such as examination findings, patient preferences, incontinence symptoms, and surgeon practice. Evidence surrounding staged versus concomitantMUS procedures (sMUS vs cMUS, respectively) is mixed. This study sought an estimation of cost utility of sMUS versus cMUS strategy among patients undergoing apical suspension for POP. The study created a decision analysis model (TreeAge Pro,Williamstown, MA) for comparison of cost utility of sMUS versus cMUS strategies across a 1-year time frame. Payer perspective was the focus of analysis. Six separate models were run representing 2methods of apical prolapse surgery (minimally invasive sacrocolpopexy [MISC] or vaginal native tissue apical suspension ) for each of 3 clinical scenarios for urinary continence status (preoperative symptomatic SUI, preoperative occult SUI, and no evidence of SUI). Preexisting SUI was recorded for women with objective and subjective SUI signs, whereas those lacking objective and subjective complaints were recorded without preexisting SUI. Possible adverse postoperative outcomes included urinary retention, mesh exposure, de novo overactive bladder, and persistent SUI. Incorporated into the cost-analysis were costs of pelvic floor physical therapy for postoperative SUI or de novo overactive bladder, incontinence pads, and weeks of anticipated needs. Discounting was not included in the model because of the relatively short time horizon. The main study outcome was the incremental cost-effectiveness ratio (ICER) ofMUS. Strategies with an ICER below a willingness to pay threshold of $100,000 were considered cost-effective. Preferred strategies were any with higher utility and ICERs below this threshold, whereas dominated strategieswere bothmore expensive and less effective. The modelwas individually run for each scenario, resulting in 6 individual models with 6 different cost-utility results. Regardless of route of POP repair and preoperative SUI status, the sMUS approach consistently had lower costs due to the reduction in overall numbers of MUS placed. Costs ranged from $239 to $1326 for the sMUS strategies and $2914 to $2962 for the cMUS strategies. Five of the models had higher utility than the model for women with preoperative overt SUI undergoing MISC with sMUS, which exhibited the lowest overall utility of 0.79. The model of women with no preoperative SUI undergoing vaginal native tissue suspension with sMUS exhibited the highest utility of 0.93. Staged MUS was the dominant strategy (most cost-effective) for women without any evidence of preoperative SUI in this analysis. In contrast, a concomitant sling approach was cost-effective for women with either overt or occult preoperative SUI, regardless of surgical approach for POP repair. Sensitivity analysis indicated that varying factors, such as postoperative risk of SUI, risk of adverse events, and costs, did not impact these findings. This model of cost-effectiveness is intended to aid in physician-patient counseling for this complex topic related to a common condition in women's health.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Sassine, D., et al. (2022). "Safety and Efficacy of Supradiaphragmatic Lymph Node Dissection in Advanced Ovarian Cancer." Journal of Gynecologic Surgery 38(3): 202-206.
	OBJECTIVE: Postoperative gross residual disease after cytoreductive surgery for advanced ovarian cancer impacts patient survival negatively. Specifically, unresected enlarged, metastatic supradiaphragmatic lymph nodes (SDLNs) may worsen progression-free survival (PFS) and overall survival (OS). Multiple studies have shown that upper abdominal debulking during primary cytoreductive surgery improves survival outcomes, but the evidence for resection of SDLN metastasis is less definitive. This review focuses on the feasibility, safety, and efficacy of SDLN resection for metastatic disease in advanced-stage ovarian cancer and explores emerging data on survival outcomes. MATERIALS AND METHODS: A literature review from January 2004 to December 2021 identified 4 relevant studies, all published after 2016. Eligible studies included patients with advanced ovarian, tubal, or peritoneal cancer who had undergone SDLN resection using a transdiaphragmatic approach or video-assisted thorascopy, and had evaluated SDLN dissection for diagnoses and treatment or assessed the benefits of SDLN resection as it relates to prognosis. RESULTS: All 4 studies demonstrated the feasibility and safety of SDLN resection. Three of the studies reported a low intrathoracic recurrence rate after intrathoracic debulking. Cowan et al. described an impressive median PFS and OS of 17.2 months and 70.1 months, respectively, in patients who had undergone SDLN resection. CONCLUSIONS: Resection of enlarged SDLNs in carefully selected patients has the potential to confirm intrathoracic disease spread, help achieve maximal cytoreduction without delaying adjuvant treatment, and improve survival. More studies are needed to quantify the survival benefit of SDLN resection. (J GYNECOL SURG 38:202).

Sato, H., et al. (2023). "Mirabegron versus vibegron in previously untreated female patients with overactive bladder: a randomized, single-clinic, open-label trial." Lower urinary tract symptoms 15(4): 129‐138.
	Objectives: This study aimed to assess the efficacy and safety of mirabegron compared with vibegron (both 50 mg once daily) in Japanese female patients with symptoms of overactive bladder (OAB). Methods: This prospective, 12‐week, two‐arm, parallel‐group, open‐label randomized trial (UMIN000038288) was conducted at a single clinic from December 2019 to September 2022. The primary efficacy outcome measure was the change in mean total overactive bladder symptom scores (OABSSs) from baseline to end of treatment (EOT) (Week 12). The secondary efficacy outcome measures were changes in mean International Prostate Symptom Score from baseline to EOT, the ratio of patients who achieved a minimal clinically important change (MCIC) of total OABSS, and individual domains of the King's Health Questionnaire. Safety assessments, such as adverse events (AEs), postvoid residual volume, and patient‐reported incidences, were recorded at every visit. Results: There was no statistically significant adjusted mean difference between mirabegron and vibegron in terms of the primary outcome of the mean change from baseline to EOT in the total OABSS. The difference in the percentage of patients in the mirabegron and vibegron groups achieving an MCIC on the total OABSS was not statistically significant but appeared to be clinically important. The incidence of treatment‐related AEs was significantly higher for the vibegron group (38.5%) than the mirabegron group (19.1%) (p =.047). Conclusions: These results showed that both drugs were effective in female OAB patients, with no significant differences in terms of efficacy. However, the safety of vibegron requires further investigation.

Sato, K. and K. Seto (2022). "The effect of Dioscorea esculenta powder on prostaglandin E 2 and cytochrome c oxidase subunit 2 levels, menstrual pain, and premenstrual syndrome in young women: A randomized double-blind controlled trial." Nutrition and health: 2601060221130889.
	Background Diosgenin, extracted from Dioscorea esculenta , has been reported to decrease prostaglandin E 2 (PGE 2 ) levels and any other inflammatory cytokine in rodents. However, it is still unclear whether D. esculenta intake suppressed PGE 2 production and menstrual pain and premenstrual syndrome (PMS) in younger female. Aim This study aims to investigate the effect of D. esculenta intake on PGE 2 and cytochrome c oxidase subunit 2 (COX-2) levels and on menstrual pain and PMS in young women. This is a randomized, double-blind, placebo-controlled, crossover study. Methods Ten healthy young females were administered either a placebo or D. esculenta (300 mg/day) for 4 weeks, followed by a 4-week washout period. Fasting blood sample was taken from the fingertips on the second day of menstrual cycle began and obtained 24h before the last D. esculenta to avoid acute effects. Participants then switched treatments for 4 weeks as a second trial. Plasma PGE 2 and COX-2 levels were measured before and after each trial. The visual analogue scale (VAS), McGill pain questionnaire (MPQ), and Daily Record of Severity of Problems (DRSP) were also evaluated. The study was set and conducted from 2019 to 2020. Results PGE 2 and COX-2 levels significantly decreased after D. esculenta intake compared to placebo ( p = 0.038, p = 0.042 each). The VAS and DRSP scores were also significantly lower after D. esculenta intake ( p = 0.046, p = 0.035 each). Conclusion Four-week D. esculenta intake suppressed PGE 2 and COX-2 levels resulting in an improvement in PMS symptoms and menstrual pain in young women.

saul, d. and q. Stephany (2022). "Preoperative assessment of urinary incontinence with clinical evaluation in the office or urodynamic test as a predictor of outcome after correction of pelvic organ prolapse: A systematic review and meta-analysis."
	
Saupstad, M., et al. (2019). "Preparation of the endometrium and timing of blastocyst transfer in modified natural cycle frozen-thawed embryo transfers (mNC-FET): a study protocol for a randomised controlled multicentre trial." BMJ Open 9(12): e031811.
	Introduction: Despite the high number of frozen embryo transfer (FET) cycles being conducted (190 000 cycles/year) in Europe, the timing of blastocyst transfer and the use of luteal phase progesterone support in modified natural cycle FET (mNC-FET) in assisted reproductive technologies are controversial. In mNC-FET, the timing of blastocyst warming and transfer is determined according to the time of implantation in a natural cycle, aiming to reach blastocyst endometrial synchronicity. However, the optimal day of blastocyst transfer following ovulation trigger is not determined. In addition, the value of luteal phase support to maintain the endometrium remains uncertain. Thus, there is a need to identify the optimal timing of blastocyst warming and transfer and the effect of luteal phase support in a randomised controlled trial design. The aim of this randomised controlled trial is to investigate if progesterone supplementation from the early luteal phase until gestational age 8 weeks is superior to no progesterone supplementation and to assess if blastocyst warming and transfer 6 days after ovulation trigger is superior to 7 days after ovulation trigger in mNC-FET with live birth rates as the primary outcome.; Methods and Analysis: Multicentre, randomised, controlled, single-blinded trial including 604 normo-ovulatory women aged 18-41 years undergoing mNC-FET with a high-quality blastocyst originating from their first to third in vitro fertilisation/intracytoplasmic sperm injection cycle. Participants are randomised (1:1:1:1) to either luteal phase progesterone or no luteal phase progesterone and to blastocyst warming and transfer on day 6 or 7 after human chorionic gonadotropin trigger. Only single blastocyst transfers will be performed.; Ethics and Dissemination: The study is approved by the Danish Committee on Health Research Ethics (H-18025839), the Danish Medicines Agency (2018061319) and the Danish Data Protection Agency (VD-2018-381). The results of the study will be publicly disseminated.; Trial Registration Number: The study is registered in EudraCT (2018-002207-34) and on ClinicalTrials.gov (NCT03795220); Pre-results.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Savannah, C., et al. (2022). "Medical Marijuana Use and Endometriosis Symptom Management: A Systematic Review."
	
Savannah, S., et al. (2023). "The effectiveness of non-pharmaceutical interventions for women with polycystic ovary syndrome: a systematic review and meta-analysis."
	
Savaris Ricardo, F., et al. (2019). "Antibiotic therapy for pelvic inflammatory disease: an abridged version of a Cochrane systematic review and meta-analysis of randomised controlled trials." Sexually Transmitted Infections 95(1): 21-27.
	Objective: To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID).; Design: This is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.; Data Sources: Eight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature.; Eligibility Criteria: RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment.; Results: We included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed.; Conclusions: We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.; Competing Interests: Competing interests: RFS, DGF, RVD and SF certify that they do not have any affiliations with, or involvement in, any organisation or entity with a direct financial interest in the subject matter of this review (eg, employment, consultancy, stock ownership, honoraria, expert testimony). JR declares the following interests: personal fees from GSK Pharma, Hologic Diagnostic and Janssen Pharma; ownership of shares in GSK Pharma and AstraZeneca Pharma; author of the UK and European Guidelines on Pelvic Inflammatory Disease; member of the European Sexually Transmitted Infections Guidelines Editorial Board; member of the National Institute for Health Research (NIHR) HTA Commissioning Board; NIHR Journals Editor; Editorial Board of the Cochrane Collaboration Sexually Transmitted Diseases Collaborative Review Group; and Sexually Transmitted Infections journal associate editor. The authors disclose that two of the authors (RFS and JR) had two publications used in the analysis. RFS and JR did not participate in the process for considering these studies for inclusion, data extraction, quality assessment and grading for risk of bias. The current article is based on a published Cochrane review. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Savci, B., et al. (2022). "Oral Gonadotropin Releasing Hormone Antagonists In The Treatment Endometriosis: A Systematic Review and Network Meta-Analysis of Efficacy Parameters and Adverse Effects."
	
Savci, B., et al. (2021). "Oral gonadotropin releasing hormone antagonists in the treatment of uterine fibroids: a systematic review and network meta-analysis of efficacy parameters and adverse effects."
	
Sávia, D., et al. (2021). "The Effectiveness of Functional Elastic Bandage on Female Pelvic Discorders: A Review of Randomized, Controlled Clinical Trials."
	
Savia, D., et al. (2021). "Use of Essential Oils Associated with Physiotherapy for Pain Relief in Dysmenorrhea: A Systematic Review."
	
Sayahi, M., et al. (2023). "Is there a difference between the effects of phytoestrogens and non-phytoestrogens medicinal plants on sexual health? A systematic review and meta-analysis." International Journal of Reproductive Biomedicine 21(11): 881-900.
	Background: The quality of life of a person and her sexual partner is impacted by sexual function. Sexual function disorders have a significant prevalence in society. There are different treatments for sexual disorders, including herbal therapies. Objective(s): This study aimed to do a comparison of phytoestrogens and non-phytoestrogens medicinal plant's effects on sexual health in pre-and postmenopausal women. Material(s) and Method(s): This systematic review and meta-analysis was performed to identify relevant articles in electronic databases such as Web of Science, Scopus, PubMed, Cochrane Library, Google Scholar, and SID for English-and Persian-language articles published up to December 2021. The Cochrane collaboration tool was used to assess the risk of bias. Heterogeneity was assessed using I2 statistics. Result(s): Of 5428 records retrieved by searching the databases, after removing duplicate and irrelevant articles, 39 articles were included based on the inclusion criteria in the study. Finally, 18 articles with 1299 participants were included in the meta-analysis. 18 randomized clinical trial studies of phytoestrogens (n = 13) and non-phytoestrogens (n = 5) plants that used the female sexual function index questionnaire and reported the mean difference (MD) and standard deviation were included in the meta-analysis. The effects of phytoestrogens and non-phytoestrogens plants on the sexual health of postmenopausal women appear to differ significantly from one another, according to the meta-analysis (MD = 7.59; 95% CI = 4.56-10.60 and MD = 3.19; 95% CI = 1.25-5.13, respectively) but this difference was not observed in premenopausal women. Conclusion(s): The effect of phytoestrogens plants is more in menopausal women, and they can be advised to use these herbs.Copyright © Sayahi et al.

Sayedali, E., et al. (2022). "Combined Hormonal Replacement Therapy and The Risk of Endometrial Cancer in Postmenopausal Women: A Meta-analysis." Indian Journal of Gynecologic Oncology 20(4): 41.
	Background: Hormonal therapy is considered an effective treatment for relieving postmenopausal symptoms. The conflicting evidence regarding the use of hormonal therapy and the risk of endometrial cancer in postmenopausal women made their clinical use is controversial. This meta-analysis aims to find the association between combined hormonal replacement therapy and endometrial cancer in postmenopausal women. Method(s): PubMed/Medline, Cochrane Library, Google Scholar, Francis Online, and Oxford Academic Journal were researched. Case-control studies or randomized control trials were included when participants should be exposed to hormonal therapy for not more than 10 years. Result(s): After initial screening, 180 relevant studies were found, of which, 15 studies were included. The total number of women using continuous hormonal therapy (case group) was 25,827, while the number of nonusers (control group) was 56,537. Pooled statistical analysis revealed that the control group that never use hormonal replacement therapy showed a higher risk (17%) of developing endometrial cancer compared to the users of the continuous hormonal replacement therapy group (2.4%) with (p = 0.0005, OR = 0.71, 95% Cl 0.59-0.86). Conclusion(s): Continuous using of combined hormonal replacement therapy may decrease the risk of developing endometrial cancer in postmenopausal women.Copyright © 2022, The Author(s) under exclusive licence to Association of Gynecologic Oncologists of India.

Scaletta, G., et al. (2020). "Comparison of minimally invasive surgery with laparotomic approach in the treatment of high risk endometrial cancer: A systematic review." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 46(5): 782-788.
	Objective: To analyze all published studies comparing minimally invasive surgery (MIS) with laparotomic one in the surgical treatment of high-risk endometrial cancer (EC) in term of operative, peri-operative and oncological outcomes.; Data Sources: We conducted a systematic literature search in PubMed between January 1995-March 2019.; Methods of Study Selection: Titles and abstracts were analyzed by two reviewers. A set of explicit criteria was used for selection of literature: 1) randomized controlled trials (RCT), prospective or retrospective cohort studies, given the rarity of this tumor and the concomitant lack of data in the form of large trials, all reviewed original report publications with an appropriate number of subjects were considered and included; 2) participants of interest being patients who have suffered from high risk EC 3) the outcome measures including overall survival (OS), disease-free survival (DFS) and recurrence, (4) English language, (5) abstract available.; Results: Thirty relevant articles were selected for full reading. For final analysis 20 studies were selected. Then, as second step, the full articles were evaluated to determine whether full inclusion criteria were met. In total, 9 papers were identified and included.; Conclusion: MIS appears to be safe in the management of high-risk EC patients, showing better perioperative and postoperative outcomes and comparable oncological outcomes than open surgery. Prospective randomized trial would be needed to confirm this data.; Competing Interests: Declaration of competing interest Authors declare to have nothing to disclose. (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Scambia, G., et al. (2022). "Randomized phase III trial on trabectedin (ET-743) single agent versus clinician's choice chemotherapy in recurrent ovarian, primary peritoneal, or fallopian tube cancers of BRCA-mutated or BRCAness phenotype patients (MITO23)." Journal of Clinical Oncology 40(17 Supplement).
	Background: Trabectedin demonstrated antitumor activity when administered as single agent in relapsed platinum sensitive ovarian cancer (OC), with an overall response rate (ORR) ranging from 26 to 43% and a median PFS of 5 months. In addition, trabectedin showed 39.4% RR, 4.5 months median progression free survival (PFS) and 18 months median overall survival (OS) in a single arm phase 2 trial in recurrent BRCA mutated and/or the BRCAness phenotype OC patients. Method(s): In this open-label, phase III, randomized trial, we assigned recurrent OC patients harboring BRCA 1/2 mutations or with BRCAness phenotype (defined as patients who had received and responded to at least 2 previous platinum-based treatments) to receive trabectedin 1.3 mg/mq q 21d or physician's choice chemotherapy (among carboplatin, gemcitabine, weekly paclitaxel, pegylated liposomal doxorubicine or topotecan). The primary endpoint was OS. Secondary endpoints were PFS, ORR and Duration of Response (DoR). The sample size was calculated based on the assumption that trabectedin would increase median OS from 10 to 15 months (two-sided log-rank test at the error alfa= 0.05 and a power of 80%). Medians and lifetables were computed using the Kaplan-Meier method and analyzed using the log-rank test. Cox proportional hazards model was used to assess the effect of treatment. Result(s): Two hundred and forty-four patients were randomized and analyzed based on the intent-to-treat principle. At a median follow up of 40 months, the median PFS was 4.4 and 4.9 months (HR= 1.03 p=0.848) and median OS was 17.9 and 15.8 months (HR=1.15 p=0.304), in the control and experimental arm, respectively. ORR was 20.2% in the group of patients receiving standard chemotherapies and 15.4% in the group of patients treated with trabectedin. No superior effect was reported for Trabectedin in the pre-specified sub-group analysis according to BRCA mutational status, type of chemotherapy and platinum- free interval. No new signal of toxicity were reported for all the chemotherapies employed. Conclusion(s): Trabectedin as single agent does not improve survival outcomes when compared to standard chemotherapy in BRCA mut and BRCAness phenotype OC patients.

Scambia, G., et al. (2023). "SELINEXOR MAINTENANCE FOR PATIENTS WITH TP53WT ADVANCED OR RECURRENT ENDOMETRIAL CANCER: LONG-TERM FOLLOW UP OF EFFICACY AND SAFETY SUBGROUP ANALYSIS OF THE ENGOT-EN5/GOG-3055/ SIENDO STUDY." International Journal of Gynecological Cancer 33(Supplement 4): A5.
	Introduction Molecular characterization is important to inform treatment decisions for patients with endometrial cancer (EC). Wild type TP53 (TP53wt) is found in ~50% of advanced/ recurrent EC and of those, ~70% are microsatellite stable (MSS/pMMR). Methods ENGOT-EN5/GOG-3055/SIENDO (NCT03555422) is a randomized double-blind, phase 3 trial evaluating selinexor vs placebo as a maintenance treatment for advanced/ recurrent EC following response to prior systemic therapy. Here we report the updated efficacy and safety of a prespecified exploratory subgroup analysis of patients with TP53wt EC. Results 113 patients with TP53wt EC received selinexor (n=77) or placebo (n=36) as maintenance therapy. As of March 2023, the median follow-up was 25.3 months, and 26 patients remain on treatment. Median PFS (mPFS) was 27.4 months with selinexor vs 5.2 months with placebo (HR 0.42; 95% CI [0.25-0.70], nominal one-sided p=0.0003). PFS improvement was observed regardless of microsatellite instability status; in the TP53wt/MSS(pMMR) subgroup, the mPFS was not reached with selinexor vs 4.9 months with placebo. In patients with TP53wt, the most common adverse events (AEs) were nausea, vomiting, and diarrhea; most common grade >=3 AEs were neutropenia, thrombocytopenia, and nausea; 16% of patients discontinued selinexor due to AEs. No grade 5 AEs occurred. No immune-related AEs were observed. Conclusion/Implications TP53wt status may represent a robust predictive biomarker for selinexor efficacy in EC. Additionally, a strong PFS signal was observed in the TP53wt/MSS(pMMR) subgroup, a patient population with high unmet need. Both additional data and updated data will be presented at the conference.

Scarpelli, E., et al. (2022). "Minimally invasive surgery in gynecological cancers: update and systematic review." Clinical and Experimental Obstetrics and Gynecology 49(4): 88.
	Introduction: In the last decades, the introduction of laparoscopy and, more recently, of robotic surgery, offered new options for surgical treatment also in gynecological malignancies, as an alternative to open surgery. When considering the best surgical treatment option for gynecological malignancies, evidence about safety, feasibility, and oncological outcomes must be taken into account, to offer the best treatment to the patient. The present review aims to provide an updated scenario over the available evidence in the use of minimally invasive surgery (MIS) in gynecological malignancies. Material(s) and Method(s): An electronic search was performed using the following keywords: 'minimally invasive surgery' and 'gynecology', 'minimally invasive surgery' and 'endometrial cancer', 'minimally invasive surgery' and 'ovarian cancer', 'minimally invasive surgery' and 'cervical cancer'. The agreement about potential relevance was reached by consensus of the researchers and according to PRISMA statement guidelines. Systematic reviews, meta-analyses, clinical trials, and original articles were included in the present review. Result(s): Fifty-eight studies were considered eligible for the study, 23 studies regarding MIS in endometrial cancer (EC), 19 studies on MIS in ovarian cancer (OC), and 16 studies regarding MIS in cervical cancer (CC). The total of patients enrolled was 180,057, 131,430 in the EC group, 23,774 in the OC groups, and 24,853 in the CC group. Conclusion(s): According to the available evidence and current clinical practice, MIS is undoubtedly the gold standard for early-stage EC treatment and may represent an acceptable option even in high-risk EC patients. Concerning OC, MIS is a safe and useful tool for staging purposes in advanced-stage disease, and a treatment option only in high volume centres with expert oncologic surgeons. On the contrary, MIS should be abandoned in the context of CC, exception made for well-selected patients, who received adequate counselling about current evidence.Copyright © 2022 S.O.G. CANADA Inc.. All rights reserved.

Schaafsma, M., et al. (2022). "Is less more in the surgical treatment of early-stage cervical cancer?" Current Opinion in Oncology 34(5): 473-489.
	Purpose of Review: This article discusses recent developments towards less radical surgical treatment for early-stage cervical cancer.; Recent Findings: Surgery is the standard treatment for early-stage cervical cancer. In the last decades, new treatment strategies have been developed aiming to reduce morbidity, without hampering oncological safety. We provide an update of the latest knowledge on safety and morbidity following less radical surgical procedures in early-stage cervical cancer. In cervical cancer with a tumour size of 2 cm or less, radical surgery (simple hysterectomy or fertility-sparing conisation) may be a well tolerated option. For patients with larger lesions (>2 cm) and wishing to preserve fertility, administration of neoadjuvant chemotherapy followed by less extensive surgery appears to be a feasible and well tolerated alternative to abdominal trachelectomy. With regard to lymph node assessment, increasing evidence shows the feasibility of the sentinel lymph node procedure instead of full pelvic lymphadenectomy. Prospective trials reporting on oncological safety are awaited.It is important to exercise caution when new surgical strategies are introduced. Despite promising retrospective data, prospective randomized studies may present unexpected results, for instance, minimally invasive radical hysterectomy showed inferior results compared to laparotomy.; Summary: There is a shift towards less radical treatment for early-stage cervical cancer. This review explores whether and when less is really more. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Scharl, S., et al. (2023). "Intracavitary brachytherapy with additional Heyman capsules in the treatment of cervical cancer." Archives of Gynecology and Obstetrics 307(2): 557-564.
	Purpose: Brachytherapy is a mandatory component of primary radiochemotherapy in cervical cancer. The dose can be applied with a traditional intracavitary approach (IC alone) or with multiple catheter brachytherapy to optimize dose distribution in an individual concept. We therefore evaluated whether the utilization of a tandem-ring applicator plus additional intracavitary applicators (add IC) provides an advantage over the traditional IC alone approach, as this method is less time consuming and less invasive compared to a combined intracavitary/interstitial brachytherapy.; Methods: Twenty three procedures of intracavitary brachytherapy for cervical cancer with additional intracavitary applicators performed in seven patients treated between 2016 and 2018 in our institution were included in this study. Plans were optimized for D90 HR-CTV with and without the utilization of the additional applicators and compared by statistical analysis.; Results: D90 for HR-CTV was 5.71 Gy (±1.17 Gy) for fractions optimized with add IC approach and 5.29 Gy (±1.24 Gy) for fractions without additional applicators (p < 0.01). This translates to a calculated mean EQD2 HR-CTV D90 of 80.72 Gy (±8.34 Gy) compared to 77.84 Gy (±8.49 Gy) after external beam therapy and four fractions of brachytherapy for add IC and IC alone, respectively (p < 0.01). The predictive value of improved coverage of HR-CTV in the first fraction was high.; Conclusion: In a subgroup of cases, the addition of intracavitary Heyman capsules can be an alternative to interstitial brachytherapy to improve the plan quality compared to standard IC alone brachytherapy. The benefit from the addition of applicators in the first fraction is predictive for the following fractions. (© 2022. The Author(s).)

Schenk, M., et al. (2021). "Effect of probiotics on vaginal Ureaplasma parvum in women suffering from unexplained infertility." Reproductive Biomedicine Online 43(3): 503-514.
	RESEARCH QUESTION: Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women experiencing infertility? DESIGN: A prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included. Patients were assigned to either a probiotic treatment or a control group. Participants in the treatment group (n = 40) took one sachet (2 g) a day of a defined probiotic supplement limiting Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20, of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples was conducted. RESULTS: After the intervention phase, no effects on alpha diversity resulting from treatment could be observed. The between sample diversity of different women (beta diversity) at baseline had no effects of age, treatment group or body mass index. Primary or secondary sterility, however, had a significant effect on community. Three clusters (Lactobacillus crispatus, Lactobacillus iners and Lactobacillus gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed limited growth of Ureaplasma parvum compared with the control group (P = 0.021). CONCLUSIONS: This study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.

Schimmel, N., et al. (2022). "Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review." Psychopharmacology 239(1): 15-33.
	Background: Terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. Existing psychotherapeutic or pharmacological interventions have (time) limited efficacy. Psychedelic treatment may be a safe and effective alternative treatment option. Aim(s): Systematically review studies on psychedelic treatment with and without psychotherapy for existential distress, depression, and anxiety in terminally ill patients. Method(s): Medline, PsycINFO, and Embase were searched for original-data studies on the treatment of depression, anxiety, and existential distress with classical or a-typical psychedelics in patients with a terminal illness, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Result(s): A total of 1850 records were screened, and 33 articles were included in this review: 14 studies on classical psychedelics (DPT, LSD, and psilocybin) and 19 studies on atypical psychedelics (MDMA and ketamine). Results of early pre-post studies are promising but have serious methodological flaws. Recent (controlled) trials with LSD, psilocybin, ketamine, and MDMA are of higher methodological quality and indicate positive effects on existential and spiritual well-being, quality of life, acceptance, and reduction of anxiety and depression with few adverse and no serious adverse effects. Conclusion(s): Both classical and a-typical psychedelics are promising treatment options in patients with terminal illness. To draw final conclusions on effectiveness and safety of psychedelics, we need larger high-quality studies for classical psychedelics and MDMA. Ketamine studies should pay more attention to existential dimensions of well-being and the psychotherapeutic context of the treatment.Copyright © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Schlaeger Judith, M., et al. (2022). "Protocol for double-blind RCT of acupuncture for vulvodynia." Contemporary clinical trials communications 30: 101029.
	Background: Vulvodynia, vulvar pain of unknown origin lasting at least 3 months, affects 7% of American women. Dyspareunia, its frequent companion, renders sexual intercourse virtually impossible. Although few therapies are efficacious and rapid pain relief is rarely possible, there have been no sham/placebo-controlled studies of acupuncture for vulvodynia. Aims are to: 1) determine efficacy of acupuncture for vulvodynia, 2) explore duration of the acupuncture effect.; Methods: In a pretest/posttest randomized controlled, double-blind (practitioner-patient) efficacy trial of a standardized acupuncture protocol, we will randomize 80 participants 1:1 to either penetrating needle or skin-touch placebo needle groups. Both types of needles are designed to blind both the acupuncturist and participant. Participants with vulvodynia will insert and remove a tampon as a standardized stimulus and complete primary measures of vulvar pain (pain intensity) and secondary measures of dyspareunia (Female Sexual Function Index, FSFI dyspareunia subscale score) and sexual function (FSFI total score) pretreatment, after the 10th acupuncture session, and pain measures weekly until return to pretest levels. Upon study completion control group participants will be offered 10 free real acupuncture sessions.; Discussion: This is the first multi-needle multi-session RCT using double-blind acupuncture needles as a reliable sham. We hypothesize that controlling for baseline, at posttest there will be statistically significant less vulvar pain and dyspareunia and more sexual function over five weeks in the penetrating needle group compared to the skin touch placebo group.; Conclusion: This study is responsive to the need for efficacious pain management for women with vulvodynia.ClinicalTrials.gov Identifier: NCT03364127.; Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Nobuari Takakura and the Educational Foundation of Hanada Gakuen possess a US patent 6575992B1, a Canadian patent CA 2339223, a Korean patent 0478177, a Taiwan patent 150135, a Chinese patent ZL00800894.9 (Title: Safe needle, placebo needle and needle set for double blind), and two Japanese patents 4061397 (Title: Placebo needle, and needle set for double-blinding) and 4315353 (Title: Safe needle) on the needles described in this abstract. Dr. Takakura is a salaried employee of the Educational Foundation of Hanada Gakuen. Dr. Diana J. Wilkie is the founder and chairman of eNURSING LLC, a company without current ownership of the PAINReportIt software. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. (© 2022 The Authors.)

Schlaff, W., et al. (2023). "Elagolix with Add-Back Therapy Improves Hemoglobin Concentration in Women with Fibroid-Associated Heavy Menstrual Bleeding Across Subgroups: Post Hoc Analysis of Elaris UF-1 and UF-2." Obstetrics and Gynecology 141(5 Supplement 1): 13S-14S.
	INTRODUCTION: Premenopausal patients with fibroid-associated heavy menstrual bleeding often experience anemia-related symptoms and reduced quality of life. Here, we report the effect of elagolix with estradiol/norethindrone acetate add-back therapy (ELA+AB) on hemoglobin (Hgb) concentration across subpopulations of patients at 6 months of treatment. METHOD(S): This post hoc analysis from duplicate, IRB-approved, randomized, double-blind, placebo-controlled, 6-month phase 3 Elaris UF-1/UF-2 studies (NCT02654054/NCT02691494) evaluated Hgb improvement from baseline to 6 months of therapy by change in Hgb concentration and proportion of patients who achieved greater than 1 and greater than 2 g/dL improvement by subgroups (race, age, primary International Federation of Gynecol-ogy and Obstetrics [FIGO] score, and baseline menstrual blood loss volume) in prespecified anemic subpopulations (baseline Hgb#10.5 and 10.5 to #12 g/dL). RESULT(S): Overall, baseline demographics and clinical characteristics were balanced between groups. Regardless of subgroup, patients with mean baseline Hgb less than 10.5 g/dL receiving ELA+AB experienced significant improvements in mean Hgb concentration at 6 months, compared with placebo (P,.001; no adjustment for multiple comparisons were made). These patients had a mean Hgb concentration of 11.6 g/dL at 6 months, with a range of 11.3-12.3 g/dL depending on subgroup. At 6 months, 47% of these patients had an increase of greater than 2 g/dL with a range of 41-59% depending on subgroup. CONCLUSION(S): ELA+AB was effective in improving Hgb concentration across subgroups of premenopausal women with uterine fibroids and anemia (Hgb,10.5 g/dL), regardless of baseline demographics or clinical characteristics, which may therefore alleviate symptoms and reduce complications of anemia.

Schmerold, L., et al. (2024). "A cost-effectiveness analysis of intrauterine spacers used to prevent the formation of intrauterine adhesions following endometrial cavity surgery." Journal of Medical Economics 27(1): 170-183.
	Aim: To assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery. Material(s) and Method(s): A decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results. Result(s): In this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan. Limitation(s): There are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided. Conclusion(s): This analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.Copyright © 2024 Rejoni Inc. Published by Informa UK Limited, trading as Taylor & Francis Group.

Schmid, F. A., et al. (2023). "Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial." International Urogynecology Journal 34(9): 2197-2206.
	Introduction and hypothesis: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. Method(s): Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. Result(s): Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). Conclusion(s): Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.Copyright © 2023, The Author(s).

Schmidt Mona, W., et al. (2023). "Effects of intermittent fasting on quality of life tolerance of chemotherapy in patients with gynecological cancers: study protocol of a randomized-controlled multi-center trial." Frontiers in Oncology 13: 1222573.
	Fatigue is a very common side effect during intravenous chemotherapy. Unfortunately, only few effective therapeutic options are available, mostly based on daily activity. In our pilot trial we were able to demonstrate that intermittent fasting can reduce fatigue in healthy people, thus we aimed to assess the effects of the fasting dietary on quality of life during chemotherapy in patients with gynecological cancer, especially on the domain of fatigue. The IFAST trial is designed as a prospective, randomized-controlled, multi-center trial. Participation will be offered to women with gynecological cancers (breast cancer, ovarian cancer including peritoneal and fallopian tube cancers, endometrial cancer and cervical cancer) who are planned to receive intravenous chemotherapy for at least three months. Eligible patients will be randomized 1:1, stratified by tumor type and study center. Primary endpoint is the difference in mean change in fatigue, assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT- FS © ). Exploratory secondary endpoints will include general Quality of Life impairment, tolerance of chemotherapy, immunological changes, peripheral cell damage in blood cells, as well as tumor response to chemotherapy. There is new evidence that prolonged fasting periods of 46-96 hours during chemotherapy can positively influence the quality of life during chemotherapy. However, these fasting regiments are not feasible for many patients. Intermittent fasting could be a feasible (manageable) option for many patients to actively improve their quality of life and tolerance to chemotherapy and possibly even enhance the effectiveness of chemotherapy.; Trial Registration: https://drks.de, identifier DRKS00031429.; Competing Interests: MB reports honoraria and expenses from Pharma Mar AG, Astra Zeneca, TesaroBio GmbH, GSK, Roche, Clovis Oncology and consultant activity to AstraZeneca, Clovis Oncology, Eisai, GSK, MSD, PharmaMar, Roche and Tesaro Bio GmbH. Furthermore, he has received research funding by AstraZeneca, Clovis Oncology, MSD, Eisai and Novartis. None were related to this study. MS reports personal fees from AstraZeneca, BioNTech, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen outside the submitted work. Institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre-Fabre, and Roche. Travel reimbursement from Pfizer and Roche. In addition, M.S. has a patent for EP 2390370 B1 issued and a patent for EP 2951317 B1 issued. AH reports honoraria and expenses from AstraZeneca, Celgen, Leo Pharma, MedConcept GmbH, Med update GmbH, Medpublico GmbH, Pfizer, PharmaMar GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG, Tesaro Bio Germany GmbH as well as work as a consultant to MSD SHARP & DOHME GmbH, PharmaMar, Medpublico GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG and Tesaro Bio Germany GmbH. None were related to this study. RS reports honoraria and expenses from Roche Pharma AG and AstraZeneca GmbH. SS reports honoraria from Lilly, Eisai, and Pfizer as well as expenses from Kite Gilead, all outside of this trial. KAn reports paid lectures by Clovis Oncology, AstraZeneca, Pharma Mar, MSD and Eisai not related to this trial. KAl received speaker honoraria from Roche Pharma AG, Pfizer Pharma GmbH, Seagen, Med publico GmbH and AstraZeneca not related to the current work. All author authors report no conflict of interest. BB-S reports honoraria from Seagen and MSD not related to this trial. ALe reports honoraria from Astra Zeneca and Roche not related to this trial. SK received speaker honoraria from Roche Pharma AG and Novartis Pharma GmbH Germany, research funding from Novartis Pharma GmbH Germany and travel reimbursement from PharmaMar and Novartis Pharma GmbH Germany, non-related to this trial. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copy ight © 2023 Schmidt, Brenner, Gebhard, Schmidt, Singer, Weidenbach, Hahn, Puzankova, Blau-Schneider, Lehnert, Battista, Almstedt, Lütkemeyer, Radsak, Mähringer-Kunz, Krajnak, Linz, Schwab, Gabriel, Hasenburg and Anic.)

Schmidt-Hansen, M., et al. (2020). "Initiation of abortion before there is definitive ultrasound evidence of intrauterine pregnancy: A systematic review with meta-analyses." Acta Obstetricia et Gynecologica Scandinavica 99(4): 451-458.
	Introduction: Women are increasingly presenting for abortion at very early gestation. However, providers may be reluctant to conduct abortion at this stage as they may be concerned that they cannot exclude an ectopic pregnancy or that they may terminate a non-viable pregnancy, or may be concerned that both medical and surgical methods may be less effective at this stage of gestation. This provider concern may result in delays in the abortion as additional investigations may be required until an intrauterine pregnancy can be confirmed. Additional unnecessary visits may be distressing for women and waste health service resources. The objective of this systematic review was to determine whether it is safe and effective to initiate abortion before there is ultrasound evidence of an intrauterine pregnancy.; Material and Methods: We searched Embase Classic, Embase; Ovid MEDLINE® Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, Ovid MEDLINE®; and Cochrane Library on 25 October 2019. Eligible studies were randomized and non-randomized comparative studies, published in English from 1985, comparing initiation of abortion before there is definitive evidence of an intrauterine pregnancy with initiation afterwards. We assessed risk-of-bias using the Newcastle-Ottowa scale. All outcomes were analyzed as risk ratios (RR) and meta-analyzed using the Mantel-Haenszel method. The quality of the evidence was assessed using GRADE.; Results: Two non-randomized studies (n = 3785) showed no differences in "missed ectopic pregnancy" (RR = 0.26, 95% CI 0.03-2.12), "ongoing pregnancy" (RR = 1.06, 95% CI 0.34-3.34), or "complete abortion without surgical intervention" (RR = 1, 95% CI 0.98-1.02) between initiation of medical abortion before or after ultrasound evidence of an intrauterine pregnancy. A third non-randomized study (n = 1530) showed no differences between initiation of surgical abortion before or after ultrasound evidence of an intrauterine pregnancy in "missed ectopic pregnancy" (no events), "ongoing pregnancy" (RR = 0.56, 95% CI 0.03-11.59) or "complete abortion without repeat surgical intervention" (RR = 1, 95% CI 0.99-1.01). The quality of evidence was very low.; Conclusions: Initiation of abortion before there is definitive ultrasound evidence of an intrauterine pregnancy in women without signs or symptoms of an ectopic pregnancy should be considered. (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Schmidt-Hansen, M., et al. (2021). "Expulsion at home for early medical abortion: A systematic review with meta-analyses." Acta Obstetricia et Gynecologica Scandinavica 100(4): 727-735.
	Introduction: The safety and acceptability of medical abortion using mifepristone and misoprostol at home at <=9+0 weeks' gestation is well established. However, the upper gestational limit at which the procedure remains safe and acceptable at home is not known. To inform a national guideline on abortion care we conducted a systematic review to determine what gestational limit for expulsion at home offers the best balance of benefits and harms for women who are having medical abortion. Material(s) and Method(s): We searched Embase, MEDLINE, Cochrane Library, Cinahl Plus and Web-of-Science on 2 January 2020 for prospective and retrospective cohort studies with >=50 women per gestational age group, published in English from 1995 onwards, that included women undergoing medical abortion and compared home expulsion of pregnancies of <=9+0 weeks' gestational age with pregnancies of 9+1-10+0 weeks or >10+1 weeks' gestational age, or compared the latter two gestational age groups. We assessed risk-of-bias using the Newcastle-Ottowa scale. All outcomes were meta-analyzed as risk ratios (RR) using the Mantel-Haenszel method. The certainty of the evidence was assessed using GRADE. Result(s): Six studies (n = 3381) were included. The "need for emergency care/admission to hospital" (RR = 0.79, 95% confidence interval [CI] 0.45-1.4), "hemorrhage requiring transfusion/>=500 mL blood loss" (RR = 0.62, 95% CI 0.11-3.55), patient satisfaction (RR = 0.99, 95% CI 0.95-1.03), pain (RR = 0.91, 95% CI 0.82-1.02), and "complete abortion without the need for surgical intervention" (RR = 1.03, 95% CI 1-1.05) did not differ statistically significantly between the <=9+0 and >9+0 weeks' gestation groups. The rates of vomiting (RR = 0.8, 95% CI 0.69-0.93) and diarrhea (RR = 0.85, 95% CI 0.73-0.99) were statistically significantly lower in the <=9+0 weeks group but these differences were not considered clinically important. We found no studies comparing pregnancies of 9+1-10+0 weeks' gestation with pregnancies of >10+0 weeks' gestation. The certainty of this evidence was predominantly low and mainly compromised by low event rates and loss to follow up. Conclusion(s): Women who are having a medical abortion and will be taking mifepristone up to and including 10+0 weeks' gestation should be offered the option of expulsion at home after they have taken the misoprostol. Further research needs to determine whether the gestational limit for home expulsion can be extended beyond 10+0 weeks.Copyright © 2020 Nordic Federation of Societies of Obstetrics and Gynecology

Schneider, S., et al. (2020). "Prehabilitation programs and ERAS protocols in gynecological oncology: a comprehensive review." Archives of Gynecology and Obstetrics 301(2): 315-326.
	Purpose: The "Enhanced recovery after surgery" (ERAS) concept has been continuously developed for many surgical disciplines. Shorter length of stay (LOS) and associated cost savings have been achieved without an increase in the complication or readmission rate. Current guidelines helped to support an increasing standardisation of care. One innovation of the recently published update is the proposal to integrate prehabilitation (PREHAB) into the ERAS concept. On this basis, the authors provide an overview of the current data on ERAS concepts in gynecological oncology and review the evidence of prehabilitation concepts.; Methods: Systematic literature review of all comparative studies on ERAS concepts in gynecological oncology and prehabilitation undergoing abdominal cancer surgery was performed using the standard databases. Outcomes of interest included prehabilitation program composition (exercise, nutritional, and psychological interventions), duration and outcome measures used to determine impact of prehabilitation vs. standard care.; Results: Five studies reported on PREHAB programs in gynecology (three RCTs, one study protocol, one pilot study). There is no trial evaluating a pathway for patients with extensive ovarian or cervical cancer. Study protocols were heterogenous, but showed improvements in both physical and psychological parameters. ERAS protocols in ovarian cancer patients were investigated in 12 observational studies, mostly single center and only 1 RCT, in 4 studies patients with ovarian cancer or patients. Most studies showed improvement in complication rate and shorter LOS.; Discussion: PREHAB programs seem feasible in abdominal cancer surgery and may improve surgical outcome. However, there is no prospective trial in gynecological oncology so far. Furthermore, there is no concept combining ERAS and PREHAB interventions. Therefore, the authors encourage the further development of both by describing in a novel treatment algorithm.

Schnittka, E., et al. (2023). "Surgical Outcomes Following Robotic Single-Site Versus Multiport Hysterectomy for Treatment of Endometrial Cancer: A Systematic Review and Meta-Analysis." Cureus 15(2): e34702.
	Robotic single-site hysterectomy (RSSH) has emerged as a novel surgical approach for the treatment of endometrial cancer and atypical endometrial hyperplasia (AEH). Current research regarding the benefits of RSSH compared to robotic multiport hysterectomy (RMPH) for these indications has been inconclusive. Our team sought to compare surgical outcomes between these two approaches of robotic hysterectomy via systematic review and meta-analysis to ensure optimal surgical practices. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Checklist guided our review. MEDLINE, Clinicaltrials.gov, and Cochrane Library were searched, yielding 59 results. Articles were filtered by title and abstract and then reviewed in full for inclusion and exclusion criteria. Inclusion criteria required that (1) studies compared outcomes for RSSH and RMPH, (2) hysterectomy was indicated for endometrial cancer or hyperplasia with atypia, and (3) studies were available in English. Excluded studies (1) compared single-site and multiport laparoscopic approaches, (2) compared robotic approaches to laparoscopic or abdominal (open) techniques, and (3) employed hysterectomy for benign conditions. Publication bias was assessed using the Egger Regression Correlation analysis. Four studies complied with the selection criteria, comprising 138 patients in the RSSH group and 259 in the RMPH group. Similar outcomes were noted across all measures, including conversion rate (relative risk [RR] = 1.84 and confidence interval [CI] = 0.99-3.43), blood loss (Cohen's d = 1.05 and Z = 18.62), operating time (Cohen's d = 0.29 and Z = 4.38), and length of hospital stay (Cohen's d = 1.06 and Z = 3.86). Publication bias was deemed minimal as indicated by Egger regression values of less than 0.05. These findings suggest that either a surgical approach or AEH with the proper standard of care can provide patients with endometrial cancer.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2023, Schnittka et al.)

Schonfeld, M., et al. (2021). "Mechanically Supporting Uterosacral Ligaments for the Relief of Provoked Vulvodynia: A Randomized Pilot Trial." Journal of Pain Research 14: 1281-1288.
	PURPOSE: Provoked vulvodynia (PV) is the most common cause of vulvar pain and dyspareunia. Although its etiology is unknown, it has been associated with musculoskeletal dysfunction. The inability of the lax uterosacral ligaments (USLs) to support the adjoining T11/L2 and S2-4 nerve plexuses is considered to cause PV. This study aimed to determine whether providing mechanical support to the USLs would improve PV. PATIENTS AND METHODS: PV patients were randomly divided into two groups. The participants in each group underwent sham manipulation (inserting a wide swab in the vagina without applying pressure) and trial manipulation (supporting the posterior fornix with a wide swab sufficiently broad to mechanically support the USLs). This was a cross-over trial, and the participants alternated between the sham and trial manipulation. Using a 0-10 visual analog pain scale (VAS), PV-associated pain levels experienced by participants were recorded during each manipulation, and the results were compared with baseline levels. RESULTS: The pain level significantly reduced with USL support compared with the baseline value and the sham manipulation pain level (P = 0.003). Pain during sham manipulation was not significantly different from that recorded at baseline. The average reduction in pain with USL support was 18.4% ± 2.2%. The manipulation order did not affect changes in the pain level during trial manipulation (P = 0.512). CONCLUSION: Applying mechanical support to the posterior fornix temporarily alleviates provoked vulvar pain in some women.

Schram Alison, M., et al. (2023). "Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial." JAMA Oncology 9(1): 29-39.
	Importance: Nonclinical studies suggest that the combination of poly(ADP-ribose) polymerase and programmed cell death 1/programmed cell death-ligand 1 inhibitors has enhanced antitumor activity; however, the patient populations that may benefit from this combination have not been identified.; Objective: To evaluate whether the combination of avelumab and talazoparib is effective in patients with pathogenic BRCA1/2 or ATM alterations, regardless of tumor type.; Design, Setting, and Participants: In this pan-cancer tumor-agnostic phase 2b nonrandomized controlled trial, patients with advanced BRCA1/2-altered or ATM-altered solid tumors were enrolled into 2 respective parallel cohorts. The study was conducted from July 2, 2018, to April 12, 2020, at 42 institutions in 9 countries.; Interventions: Patients received 800 mg of avelumab every 2 weeks and 1 mg of talazoparib once daily.; Main Outcomes and Measures: The primary end point was confirmed objective response (OR) per RECIST 1.1 by blinded independent central review.; Results: A total of 200 patients (median [range] age, 59.0 [26.0-89.0] years; 132 [66.0%] women; 15 [7.5%] Asian, 11 [5.5%] African American, and 154 [77.0%] White participants) were enrolled: 159 (79.5%) in the BRCA1/2 cohort and 41 (20.5%) in the ATM cohort. The confirmed OR rate was 26.4% (42 patients, including 9 complete responses [5.7%]) in the BRCA1/2 cohort and 4.9% (2 patients) in the ATM cohort. In the BRCA1/2 cohort, responses were more frequent (OR rate, 30.3%; 95% CI, 22.2%-39.3%, including 8 complete responses [6.7%]) and more durable (median duration of response: 10.9 months [95% CI, 6.2 months to not estimable]) in tumor types associated with increased heritable cancer risk (ie, BRCA1/2-associated cancer types, such as ovarian, breast, prostate, and pancreatic cancers) and in uterine leiomyosarcoma (objective response in 3 of 3 patients and with ongoing responses greater than 24 months) compared with non-BRCA-associated cancer types. Responses in the BRCA1/2 cohort were numerically higher for patients with tumor mutational burden of 10 or more mutations per megabase (mut/Mb) vs less than 10 mut/Mb. The combination was well tolerated, with no new safety signals identified.; Conclusions and Relevance: In this phase 2b nonrandomized controlled trial, neither the BRCA1/2 nor ATM cohort met the prespecified OR rate of 40%. Antitumor activity for the combination of avelumab and talazoparib in patients with BRCA1/2 alterations was observed in some patients with BRCA1/2-associated tumor types and uterine leiomyosarcoma; benefit was minimal in non-BRCA-associated cancer types.; Trial Registration: ClinicalTrials.gov Identifier: NCT03565991.

Schreiber Anna, R., et al. (2023). "First-in-Human Dose-Escalation Study of the Novel Oral Depsipeptide Class I-Targeting HDAC Inhibitor Bocodepsin (OKI-179) in Patients with Advanced Solid Tumors." Cancers 16(1).
	(1) Background: Histone deacetylases (HDACs) play a critical role in epigenetic signaling in cancer; however, available HDAC inhibitors have limited therapeutic windows and suboptimal pharmacokinetics (PK). This first-in-human phase I dose escalation study evaluated the safety, PK, pharmacodynamics (PDx), and efficacy of the oral Class I-targeting HDAC inhibitor bocodepsin (OKI-179). (2) Patients and Methods: Patients ( n = 34) with advanced solid tumors were treated with OKI-179 orally once daily in three schedules: 4 days on 3 days off (4:3), 5 days on 2 days off (5:2), or continuous in 21-day cycles until disease progression or unacceptable toxicity. Single-patient escalation cohorts followed a standard 3 + 3 design. (3) Results: The mean duration of treatment was 81.2 (range 11-447) days. The most frequent adverse events in all patients were nausea (70.6%), fatigue (47.1%), and thrombocytopenia (41.2%). The maximum tolerated dose (MTD) of OKI-179 was 450 mg with 4:3 and 200 mg with continuous dosing. Dose-limiting toxicities included decreased platelet count and nausea. Prolonged disease control was observed, including two patients with platinum-resistant ovarian cancer. Systemic exposure to the active metabolite exceeded the preclinical efficacy threshold at doses lower than the MTD and was temporally associated with increased histone acetylation in circulating T cells. (4) Conclusions: OKI-179 has a manageable safety profile at the recommended phase 2 dose (RP2D) of 300 mg daily on a 4:3 schedule with prophylactic oral antiemetics. OKI-179 is currently being investigated with the MEK inhibitor binimetinib in patients with NRAS-mutated melanoma in the phase 2 Nautilus trial.

Schreiner, L., et al. (2021). "Transcutaneous tibial nerve stimulation to treat urgency urinary incontinence in older women: 12-month follow-up of a randomized controlled trial." International Urogynecology Journal 32(3): 687‐693.
	Introduction and hypothesis: Urgency urinary incontinence (UUI) is highly prevalent in elderly individuals and has a great impact on quality of life. Transcutaneous tibial nerve stimulation (TTNS) can be an effective treatment option for UUI in older women. Methods: This is a single‐center randomized clinical trial with a 12‐month follow‐up involving 106 women > 60 years of age. Kegel exercises and bladder retraining were performed alone or in combination with TTNS, which consisted of using a transcutaneous electrical nerve stimulator for 30 min once a week for 12 weeks with the following settings: continuous mode, 10 Hz, 200 ms, and 10 to 50 mA (according to hallux mobilization). Responders to therapy who experienced failure during follow‐up were invited for a 3‐week protocol with the same parameters as those used for the initial therapy. Patients were evaluated at baseline, 4 weeks after the 12‐week protocol, and every 3 months for 12 months, through subjective satisfaction questionnaires, a 3‐day bladder diary and the International Consultation on Incontinence Questionnaire‐Short Form. King’s Health Questionnaire was applied pretreatment and 4 weeks after the last session of the 12‐week protocol. Results: A total of 101 women completed the initial 12‐week protocol. TTNS patients reported 66.7% subjective global satisfaction vs. 32.0% in the control group (p < 0.001). The TTNS group showed statistically significant improvement in quality of life (QoL) and UUI parameters compared with the control group. Forty‐eight patients were satisfied after the 12‐week protocol and completed the 12‐month follow‐up (32 in the TTNS group and 16 in the control group). A total of 80.5% of responders to TTNS were still satisfied at the end of the 12‐month follow‐up vs. 30.8% in the control group (p = 0.009). Conclusion: TTNS is effective at the 12‐month follow‐up for the treatment of UUI in elderly women.

Schroeder, M., et al. (2021). "A Randomized Controlled Trial of a Multimedia Patient Education Tool for Stress Versus Urgency Urinary Incontinence." Female Pelvic Medicine & Reconstructive Surgery 27(7): 403‐408.
	OBJECTIVE: The aim of this study was to determine whether there was a difference in patient education when comparing traditional conversation‐based patient counseling with multimedia‐based patient counseling about stress and urgency urinary incontinence. METHODS: Patients seeking treatment for urinary incontinence were randomized to traditional, conversation‐based counseling from a physician regarding stress and urgency urinary incontinence (control group) or view a video (multimedia) as their counseling (treatment group). A vignette‐based assessment of the patient's knowledge of stress and urgency urinary incontinence was administered as a pretest, immediate posttest, and 6‐ to 8‐week delayed posttest. The Incontinence Impact Questionnaire, short form, was used to assess quality of life and was administered at the initial visit and at the 6‐ to 8‐week follow‐up call. Patient satisfaction was recorded at the end of the initial visit using a continuous visual analog scale, and health literacy was evaluated using the Rapid Estimate of Adult Literacy in Medicine‐Short Form or Short Assessment of Health Literacy‐Spanish. RESULTS: In the 98 participants, immediate posttest scores trended toward significance between the control and treatment groups (P = 0.086). This trend was lost at the delayed posttest (P = 0.122). Both methods of education showed a significant difference between pretest, immediate posttest, and delayed posttest (P < 0.001). There were no demographic differences between groups. CONCLUSIONS: Multimedia‐based patient education represents an effective method of providing patient education regarding urinary incontinence because those who received video education showed comparable comprehension of this topic when compared with standard physician counseling. Video education can feasibly be used as an alternative to, or in conjunction with, current patient education practices in a urogynecology setting.

Schulten Sascha, F. M., et al. (2019). "Evaluation of two vaginal, uterus sparing operations for pelvic organ prolapse: modified Manchester operation (MM) and sacrospinous hysteropexy (SSH), a study protocol for a multicentre randomized non-inferiority trial (the SAM study)." BMC Women's Health 19(1): 49.
	Background: Pelvic organ prolapse (POP) affects up to 40% of parous women which adversely affects the quality of life. During a life time, 20% of all women will undergo an operation. In general the guidelines advise a vaginal operation in case of uterine descent: hysterectomy with uterosacral ligament plication (VH), sacrospinous hysteropexy (SSH) or a modified Manchester operation (MM). In the last decade, renewed interest in uterus sparing techniques has been observed. Previous studies have shown non-inferiority between SSH and VH. Whether or not SSH and MM are comparable concerning anatomical and functional outcome is still unknown. The practical application of both operations is at least in The Netherlands a known cause of practice pattern variation (PPV). To reveal any difference between both techniques the SAM-study was designed.; Methods: The SAM-study is a randomized controlled multicentre non-inferiority study which compares SSH and MM. Women with symptomatic POP in any stage, uterine descent and POP-Quantification (POP-Q) point D at ≤ minus 1 cm are eligible. The primary outcome is the composite outcome at two years of absence of prolapse beyond the hymen in any compartment, the absence of bulge symptoms and absence of reoperation for pelvic organ prolapse. Secondary outcomes are hospital parameters, surgery related morbidity/complications, pain perception, further treatments for prolapse or urinary incontinence, POP-Q anatomy in all compartments, quality-of-life, sexual function, and cost-effectiveness. Follow-up takes place at 6 weeks, 12 and 24 months. Additionally at 12 weeks, 6 and 9 months cost-effectiveness will be assessed. Validated questionnaires will be used and gynaecological examination will be performed. Analysis will be performed following the intention-to-treat and per protocol principle. With a non-inferiority margin of 9% and an expected loss to follow-up of 10%, 424 women will be needed to prove non-inferiority with a confidence interval of 95%.; Discussion: This study will evaluate the effectiveness and costs of SSH versus MM in women with primary POP. The evidence will show whether the existing PPV is detrimental and a de-implementation process regarding one of the operations is needed.; Trial Registration: Dutch Trial Register (NTR 6978, http://www.trialregister.nl ). Date of registration: 29 January 2018. Prospectively registered.

Schutyser, V., et al. (2021). "Clinical efficacy of virtual reality for acute pain and anxiety management during outpatient hysteroscopy and endometrial biopsy in subfertile patients." Human reproduction (Oxford, England) 36(SUPPL 1): i778.
	Study question: Does the use of virtual reality (VR) headsets in diagnostic office hysteroscopy (HSC) with endometrial biopsy (EB) reduce anxiety and pain scores in the patient? Summary answer: Virtual reality during office HSC do not seem to improve relaxation, anxiety, or pain scores. Physicians have a good perception of patients' pain. What is known already: Women undergoing outpatient HSC experience high levels of preoperative anxiety, which increase pain and discomfort during the procedure. The experience of pain is a complex phenomenon, which simultaneously occurs on cognitive, emotional, and behavioural levels, and is influenced by many factors. A Cochrane review failed to show a significant difference between different types of pain relief (analgesics, local anaesthetic and verbal support techniques). VR is a multisensory immersion providing an interactive high level distraction, occupying a large portion of humans' finite attentional resources (vision and audio), and leaving less cognitive capacity available to process pain. Study design, size, duration: The sample size for this prospective randomized controlled trial was calculated at 196 patients (98 per group), considering a power of at least 80% to detect superiority of adding a VR headset versus standard care, standard deviation (SD=2.0), using a two‐sided, t‐test, at significance level alpha of 0.05. The preliminary results after 1 month include a sample of 48 patients: 25 in the VR group and 23 controls. Participants/materials, setting, methods: All 48 patients suffer subfertility and underwent HSC with EB at our tertiary‐care fertility center. We used Oncomfort±, a commercially available VR autohypnosis relaxation program designed for perioperative settings. The headmounted smartphone display with headphones provides image sound distraction with suggestive hypnosis techniques incorporated. Before and immediately after the exam, both patients and surgeons fill out a questionnaire using the 10.0cm visual analog scale (VAS). Main results and the role of chance: The mean duration of HSC was 3min43sec in the VR group, (range 2‐6min), compared to 4min50 in the control group (range 1‐12minutes), which was not significantly different (p=0.09). Subjective variables of stress, anxiety and pain were evaluated at four different time points, i.e. before, during, immediately after HSC and one week later. According to VAS, stress levels did not differ significantly (p>0.05) between the VR group and the control group, or within time: 5.08 to 5.36 to 3.08 vs 4.48 to 4.83 to 2.48 before, during and after HSC respectively. Fear levels prior to HSC at 4.28 for VR patients and 3.52 for controls did not increase significantly during HSC in both groups: 4.44 vs 4.17. During HSC, pain levels increased from 1.40 to 4.720 in the VR group vs 0.65 to 4.109 (NS) in the controls, to decrease again afterwards to 2.60 vs 2.17 (NS) respectively. Physicians rated the average pain levels of VR patients as 3.32 compared to 3.0 for controls, which was significantly correlated to patients' perception (p<0,005). Patients gave a positive rating to the VR experience (satisfaction score 7.17). Limitations, reasons for caution: These are preliminary results, evaluating only a fourth of the required sample. A population selection bias could exist, as recruited patients were willing to accept VR. The very short induction period of 2 minutes could influence the effect of (immersiveness into) VR. Wider implications of the findings: Pain management in ambulatory procedures should be multimodal and should include both pharmacological and non‐pharmacological interventions. Introducing VR might increase patient tolerance for longer or more painful procedures. Offering a range of options will increase the spectrum of successful procedures in the outpatient setting and improve patient experience.

Schütze, S., et al. (2022). "The effect of pelvic floor muscle training on pelvic floor function and sexuality postpartum. A randomized study including 300 primiparous." Archives of Gynecology and Obstetrics 306(3): 785-793.
	Purpose: Although pregnancy and childbirth are physiological processes they may be associated with pelvic floor disorders. The aim of this study was to evaluate the influence of pelvic floor muscle training on postpartum pelvic floor and sexual function of primiparous.; Methods: This is a randomized prospective study including 300 primiparous women. Due to the dropout 200 women were analyzed. Inclusion criteria were the delivery of the first, mature baby, the ability to speak and understand German. The participants were evaluated by clinical examinations and questionnaires after 6 and 12 months postpartum. After 6 months, the women were randomized in two groups. Compared to the control group the intervention groups participated in 45-min pelvic floor muscle training and pelvic floor perception once a week over 6 weeks.; Results: The results of the questionnaires showed no significant differences between the groups after 12 months. A significant stronger pelvic floor muscle strength was found for the intervention group after 12 months. The improvement of the pelvic floor and sexual function over the time showed a significant improvement in both groups.; Conclusion: Supervised pelvic floor muscle training did not improve both the pelvic floor and the female sexual function in comparison to the control group. After 12 months, the pelvic floor and sexual function improved significant in all women.; Trial Registration: German Clinical Trials Register (DRKS00024725), retrospectively registrated. (© 2022. The Author(s).)

Schuurman, T., et al. (2021). "Fertility-Sparing Surgery in Gynecologic Cancer: A Systematic Review." Cancers 13(5).
	Fertility-sparing surgery (FSS) is increasingly being offered to women with a gynecological malignancy who wish to preserve fertility. In this systematic review, we evaluate the best evidence currently available on oncological and reproductive outcome after FSS for early stage cervical cancer, epithelial ovarian cancer, and endometrial cancer. An extensive literature search was conducted using the electronic databases Medline (OVID), Embase, and Cochrane Library to identify eligible studies published up to December 2020. In total, 153 studies were included with 7544, 3944, and 1229 patients who underwent FSS for cervical, ovarian, and endometrial cancer, respectively. We assessed the different FSS techniques that are available to preserve fertility, i.e., omitting removal of the uterine body and preserving at least one ovary. Overall, recurrence rates after FSS are reassuring and therefore, these conservative procedures seem oncologically safe in the current selection of patients with low-stage and low-grade disease. However, generalized conclusions should be made with caution due to the methodology of available studies, i.e., mostly retrospective cohort studies with a heterogeneous patient population, inducing selection bias. Moreover, about half of patients do not pursue pregnancy despite FSS and the reasons for these decisions have not yet been well studied. International collaboration will facilitate the collection of solid evidence on FSS and the related decision-making process to optimize patient selection and counseling.

Schwalfenberg, G. K. (2021). "N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)." Journal of Nutrition and Metabolism 2021: 9949453.
	Objective. To review the clinical usefulness of N-acetylcysteine (NAC) as treatment or adjunctive therapy in a number of medical conditions. Use in Tylenol overdose, cystic fibrosis, and chronic obstructive lung disease has been well documented, but there is emerging evidence many other conditions would benefit from this safe, simple, and inexpensive intervention. Quality of Evidence. PubMed, several books, and conference proceedings were searched for articles on NAC and health conditions listed above reviewing supportive evidence. This study uses a traditional integrated review format, and clinically relevant information is assessed using the American Family Physician Evidence-Based Medicine Toolkit. A table summarizing the potential mechanisms of action for N-acetylcysteine in these conditions is presented. Main Message. N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases. These conditions include polycystic ovary disease, male infertility, sleep apnea, acquired immune deficiency syndrome, influenza, parkinsonism, multiple sclerosis, peripheral neuropathy, stroke outcomes, diabetic neuropathy, Crohn's disease, ulcerative colitis, schizophrenia, bipolar illness, and obsessive compulsive disorder; it can also be useful as a chelator for heavy metals and nanoparticles. There are also a number of other conditions that may show benefit; however, the evidence is not as robust. Conclusion. The use of N-acetylcysteine should be considered in a number of conditions as our population ages and levels of glutathione drop. Supplementation may contribute to reducing morbidity and mortality in some chronic conditions as outlined in the article.Copyright © 2021 Gerry K. Schwalfenberg.

Schwartz, H., et al. (2022). "A pilot randomized controlled trial of a lay telephone coaching and web-based intervention for postpartum depression and anxiety: The MPOWER study." Internet interventions 31: 100597.
	Background: Mental health problems are frequent in the postpartum period, but accessible treatment options are lacking. The MPOWER study investigated whether the use of trained lay coaches could increase the uptake and effectiveness of a web-based intervention (WBI) for women with postpartum depression and/or anxiety.; Objectives: First, to compare the feasibility and acceptability of a WBI for women with postpartum depression and anxiety, with and without the addition of telephone coaching calls. Second, to estimate the effectiveness of the WBI at decreasing symptoms of depression and anxiety at 6 months, with and without coaching calls.; Methods: We conducted a pilot randomized controlled trial (RCT) that enrolled women who had recently given birth and had mild to moderate postpartum depression and/or anxiety. Study participants were provided access to the WBI. Women randomized to the intervention group also received up to 7 telephone coaching calls during the 6 months of follow up. We evaluated the feasibility of the intervention through participants' usage of the WBI, as well as the completion and fidelity of planned coach calls. We measured acceptability via two questionnaires on the usability of the WBI and participant satisfaction with the intervention. To determine the potential effectiveness of the intervention, the primary outcomes were defined as symptoms of depression and anxiety at 6 months and adjusted mean differences between groups for these outcomes were estimated using linear regression models.; Results: We recruited 52 participants (25 intervention; 27 control). At 6 months, 88 % (22/25) of participants randomized to the intervention arm and 59 % (16/27) of participants randomized to the control arm remained in the study. The intervention group had an average of 11 (95 % CI: [5, 18]) more website logins than the control group. Intervention group participants completed a mean of 6.2 coaching calls with high fidelity. The estimates of the effect of the intervention on mental health outcomes at 6-months were imprecise but point estimates and confidence intervals were consistent with a moderate beneficial effect of the intervention on both symptoms of depression and anxiety (fully adjusted effects sizes: 0.51 (95 % CI: [-0.14, 1.17]) and 0.56 (95 % CI: [-0.09, 1.22]), respectively).; Conclusions: WBIs with coaching are feasible, acceptable, and potentially effective treatment options for women with mild to moderate postpartum depression and/or anxiety. The addition of coaching calls markedly increased engagement with the WBI, but a larger RCT is needed to determine the effectiveness of such an intervention.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors.)

Schwarze, J. E., et al. (2019). "DHEA Use to Improve Likelihood of IVF/ICSI Success in Patients with Diminished Ovarian Reserve: A Systematic Review and Meta-analysis." Obstetrical and Gynecological Survey 74(9): 535-536.
	Despite advances in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), poor ovarian response (POR) remains a challenging issue. The frequency of POR is estimated to occur in 5% to 18% of IVF/ICSI cycles and has a corresponding pregnancy rate of 2% to 4%.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Schytt, E., et al. (2020). "Community-based doula support for migrant women during labour and birth: study protocol for a randomised controlled trial in Stockholm, Sweden (NCT03461640)." BMJ Open 10(2): e031290.
	Introduction: Migrant women consistently rate their care during labour and birth more negatively than non-migrant women, due to communication difficulties, lack of familiarity with how care is provided, and discrimination and prejudicial staff attitudes. They also report being left alone, feeling fearful, unsafe and unsupported, and have poorer birth outcomes than non-migrant women. Community-based doulas (CBDs) are bilingual women from migrant communities who are trained in childbirth and labour support, and who facilitate communication between woman-partner-staff during childbirth. This study protocol describes the design, rationale and methods of a randomised controlled trial that aims to evaluate the effectiveness of CBD support for improving the intrapartum care experiences and postnatal well-being of migrant women giving birth in Sweden.; Methods and Analysis: A randomised controlled trial. From six antenatal care clinics in Stockholm, Sweden, we aim to recruit 200 pregnant Somali, Arabic, Polish, Russian and Tigrinya-speaking women who cannot communicate fluently in Swedish, are 18 years or older and with no contraindications for vaginal birth. In addition to standard labour support, women are randomised to CBD support (n=100) or no such support during labour (n=100). Trained CBDs meet with women once or twice before the birth, provide emotional, physical and communication support to women throughout labour and birth in hospital, and then meet with women once or twice after the birth. Women's ratings of the intrapartum care experiences and postnatal well-being are assessed at 6-8 weeks after the birth using selected questions from the Migrant Friendly Maternity Care Questionnaire and by the Edinburgh Postnatal Depression Scale. The intervention group will be compared with the control group using intention-to-treat analyses. ORs and 95% CIs will be estimated and adjustments made if key participant characteristics differ between trial arms.; Ethics and Dissemination: The study was approved by the Regional Ethical Review Board in Stockholm (approval number: 2018/12 - 31/2).; Trial Registration Number: NCT03461640; Pre-results.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sciarrino, N. A., et al. (2020). "A Systematic Review of Intensive Empirically Supported Treatments for Posttraumatic Stress Disorder." Journal of Traumatic Stress 33(4): 443-454.
	Various clinical practice guidelines for the treatment of posttraumatic stress disorder (PTSD) have consistently identified two frontline evidence-based psychotherapies (EBPs)-prolonged exposure (PE) and cognitive processing therapy (CPT)-as well as other empirically supported treatments (EST), such as eye movement desensitization and reprocessing (EMDR) and cognitive therapy for PTSD (CT for PTSD). However, researchers and clinicians continue to be concerned with rates of symptom improvement and patient dropout within these treatments. Recent attempts to address these issues have resulted in intensive, or "massed," treatments for PTSD. Due to variability among intensive treatments, including treatment delivery format, fidelity to the EST, and the population studied, we conducted a systematic review to summarize and integrate the literature on the impact of intensive treatments on PTSD symptoms. A review of four major databases, with no restrictions regarding publication date, yielded 11 studies that met all inclusion criteria. The individual study findings denoted a large impact of treatment on reduction of PTSD symptoms, ds = 1.15-2.93, and random-effects modeling revealed a large weighted mean effect of treatment, d = 1.57, 95% CI [1.24, 1.91]. Results from intensive treatments also noted high rates of treatment completion (i.e., 0%-13.6% dropout; 5.51% pooled dropout rate across studies). The findings suggest that intensive delivery of these treatments can be an effective alternative to standard delivery and contribute to improved treatment response and reduced treatment dropout.

Science Vaginal, B., et al. (2022). Effects of Flourish HEC and BioGenesis to Improve Conception.
	No Results Available Combination Product: Flourish HEC and BioGenesis Conception at home|Change in vaginal microbiome|Change in vaginal pH|Conception within one year|Rate of live birth|Gestational age at delivery|Birthweight at delivery|Rates of pregnancy complications Female Phase 1 1 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Other FRT0322 March 20, 2023

Science Vaginal, B. and P. Medicine Center for (2021). Flourish HEC to Prevent Recurrence of BV.
	No Results Available Device: Flourish HEC Vaginal Care System (contains a class II medical device plus other unregulated components) Change in vaginal microbiome by next-generation sequencing (NGS)|Change in vaginal microbiome by Nugent scoring|BV recurrence|Change in vulvovaginal symptoms questionnaire (VSQ) self-report|Change in vaginal pH Female Not Applicable 6 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Prevention BV2P0821 November 15, 2022

Sciences, B. P. K. I. o. H. (2023). Comparison of Sacrospinous Ligament Fixation and Uterosacral Ligament Suspension for Apical Prolapse Surgery: A Randomized Clinical Trial.
	No Results Available Procedure: Sacrospinous ligament fixation|Procedure: Uterosacral Ligament Suspension Success rate of SSLF and USLS for apical suspension|Perioperative outcomes|Complications|postoperative PFDI- 20 score Female Not Applicable 194 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 394/079/080-IRC July 2025

Sciences Wake Forest University, H. (2022). HOPE Trial hCG or Progesterone Effect on Recurrent Pregnancy Loss.
	No Results Available Drug: Progesterone Pill|Drug: hCG Miscarriage|Ongoing pregnancy|Live birth rate Female Phase 2 0 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment BL3HOPE December 2025

Sciences Wake Forest University, H. and C. Institute National (2021). Trial Evaluating Feasibility and Quality of Life of Second Look Laparoscopy With Hyperthermic Intraperitoneal Chemotherapy.
	No Results Available Procedure: Second look laparoscopy reassessment surgery (SLLRS)|Drug: HIPEC with Carboplatin|Other: FACT-O Quality of Life Questionnaire Number of Patients To Succesfully Undergo Second Look Laparoscopy and Hyperthermic Intraperitoneal Chemotherapy|Quality of Life - Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire|Number of Reported Toxicities Female Phase 2 10 Other|NIH Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment IRB00066278|WFBCCC 04619|P30CA012197 December 2024

Scime Natalie, V., et al. (2019). "The effect of skin-to-skin care on postpartum depression among mothers of preterm or low birthweight infants: A systematic review and meta-analysis." Journal of Affective Disorders 253: 376-384.
	Background: Mothers of preterm or low birthweight (LBW) infants are at two to three times greater risk of postpartum depression (PPD) than mothers of healthy infants, which may be partially due to mother-infant separation during hospitalization. Skin-to-skin care could protect against PPD among these vulnerable mothers. We examined the effect of skin-to-skin care on PPD among mothers of preterm or LBW infants through a systematic review and meta-analysis.; Methods: We searched six peer-reviewed databases for prospective studies of skin-to-skin interventions that took place in neonatal intensive care units (NICUs), used a validated PPD tool, and were published in English between 1979 and 2017. Data were standardized and pooled using Hedges method in a quality-weighted meta-analysis.; Results: Eight studies detailing seven interventions met inclusion criteria. Intervention characteristics varied with duration ranging from one week to over two months, skin-to-skin sessions ranging from 15 min to 1 h, and frequency ranging from thrice daily to thrice weekly. Five PPD tools were used predominantly as continuous measures. Meta-analysis demonstrated that skin-to-skin interventions were associated with a 1.04% reduction in standardized depression scores versus standard care (p < 0.001), though high heterogeneity was evident (I 2 = 82.4%, p < 0.001).; Limitations: Studies differed markedly with respect to design and intervention features, and were methodologically limited by using continuous depressive scores (not dichotomous PPD diagnoses) as the outcome.; Conclusions: Skin-to-skin care has a small protective effect on maternal depressive scores, however the clinical relevance of this finding is arguably minimal. Additional well-designed studies are warranted to conclusively assess the effects of skin-to-skin on PPD. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Scorpion, T. and Inc (2023). First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors.
	No Results Available Drug: STX-478|Drug: Fulvestrant Part 1.1 (Dose Escalation): Number of participants who experience at least 1 Dose Limiting Toxicity (DLT)|Part 1.1 (Dose Escalation): Proportion of participants who experience at least 1 DLT during the first 28 days of treatment.|Part 1.1 (Dose Escalation): Cmax of STX-478|Part 1.1 (Dose Escalation): AUC(0-inf) of STX-478|Part 1.1 (Dose Escalation): AUC(0-t) of STX-478|Part 1.1 (Dose Escalation): AUC(0-τ) of STX-478|Part 1.1 (Dose Escalation): Change from baseline in ctDNA levels.|Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c]|Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose.|Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide.|Part 1.1 (Dose Escalation): Objective response rate (ORR).|Part 1.1 (Dose Escalation): Incidence of TEAEs/SAEs ≥ grade 2.|Part 1.1 (Dose Escalation): Frequency of TEAEs according to CTCAE v5.0 criteria.|RP2D Selection (Parts 1.2-DS and 2.1): Cmax of STX-478|RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-inf) of STX-478|RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-t) of STX-478|RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-τ) of STX-478|RP2D Selection (Parts 1.2-DS and 2.1): Change from baseline in ctDNA levels.|RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c]|RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose.|RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide|Parts 1.2-DS and 2.1 (RP2D Selection): ORR|Parts 1.2-DS and 2.1 (RP2D Selection): Frequency counts and percentages of AEs based on MedDRA and CTCAE v5.0|Parts 1.2-DS and 2.1 (RP2D Selection): Proportion of participants with DLTs.|Parts 1.2-DS and 2.1 (RP2D Selection): Change in ECOG performance status.|Parts 1.2-DE, 1.3, and 2.2 (Dose Expansion): ORR defined as the percentage of participants with partial response or complete response based on RECIST 1.1. All Phase 1|Phase 2 220 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment STX-478-101|2023-000442-41|2023-504807-94-00 June 1, 2026

Scott, A. M., et al. (2022). "Real-Time Telehealth Versus Face-to-Face Management for Patients With PTSD in Primary Care: A Systematic Review and Meta-Analysis." The Journal of Clinical Psychiatry 83(4).
	Objective: We conducted a systematic review and meta-analysis of randomized controlled trials comparing real-time telehealth (video, phone) with face-to-face therapy delivery to individuals with posttraumatic stress disorder (PTSD), by primary or allied health care practitioners. Data Sources: We searched MEDLINE, Embase, CINAHL, and Cochrane Central (inception to November 18, 2020); conducted a citation analysis on included studies (January 7, 2021) in Web of Science; and searched ClinicalTrials.gov and WHO ICTRP (March 25, 2021). No language or publication date restrictions were used. Study Selection: From 4,651 individual records screened, 13 trials (27 references) met the inclusion criteria. Data Extraction: Data on PTSD severity, depression severity, quality of life, therapeutic alliance, and treatment satisfaction outcomes were extracted. Results: There were no differences between telehealth and face-to-face for PTSD severity (at 6 months: standardized mean difference [SMD] = -0.11; 95% CI, -0.28 to 0.06), depression severity (at 6 months: SMD = -0.02; 95% CI, -0.26 to 0.22; P = .87), therapeutic alliance (at 3 months: SMD = 0.04; 95% CI, -0.51 to 0.59; P = .90), or treatment satisfaction (at 3 months: mean difference = 3.09; 95% CI, -7.76 to 13.94; P = .58). One trial reported similar changes in quality of life in telehealth and face-to-face. Conclusions: Telehealth appears to be a viable alternative for care provision to patients with PTSD. Trials evaluating therapy provision by telephone, and in populations other than veterans, are warranted.

Scutiero, G., et al. (2022). "Influence of uterine manipulator on oncological outcome in minimally invasive surgery of endometrial cancer: A systematic review and meta-analysis." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 48(10): 2112-2118.
	Aim: The endoscopic approach for early-stage endometrial cancer (EC) treatment is considered gold standard. Some authors expressed their concern regarding uterine manipulator (UM) as a risk factor for tumor spillage and dissemination allowing peritoneal or lympho-vascular spaces invasion (LVSI). This meta-analysis aimed to evaluate the effect of UM on the presence of LVSI, recurrence rate and presence of atypical or malignant peritoneal cytology in patients with endometrial cancer.; Methods: We searched electronic databases including PubMed, MEDLINE, Embase, Scopus, EBSCO, Google Scholar, and ClinicalTrials.gov. The pooled results were used to evaluate the association between the use of UM and oncological outcomes. This systematic review was reported according to PRISMA statement 2020. Statistical meta-analysis was performed using Review Manager software.; Results: This systematic review included 18 studies (3 prospective studies, 13 retrospective studies, and 2 RCT). The pooled results showed no significant difference (RR: 0.86, 95% CI, 0.69 to 1.08) in the incidence of LVSI between manipulated hysterectomy and total abdominal hysterectomy (TAH) and between UM group and non-UM group in minimally invasive surgery (RR: 1.18, 95% CI, 0.76 to 1.85), no significant difference in the rate of recurrence (RR: 1.11, 95% CI, 0.71 to 1.74), in the incidence of positive peritoneal cytology between manipulated and non-manipulated hysterectomies in minimally invasive surgery (RR: 1.89, 95% CI, 0.74 to 4.83) and before and after the use of uterine manipulator (RR: 1.21, 95% CI, 0.68 to 2.16). We found a positive association between malignant cytology and hysterectomies in which a uterine manipulator had been used in a sub-group analysis where LH/LAVH were compared to TAH. (RR = 2.26, 95% CI, 1.08-4.71. P = 0.03).; Conclusions: This meta-analysis supports that the use of uterine manipulator for minimally invasive treatment of endometrial cancer does not increase the rate of recurrence and LVSI. Therefore, the opportunity of any other studies on its use in endometrial cancer women should be questioned.; Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Se, I., et al. (2021). "Effectiveness of hyperthermic intraperitoneal chemotherapy after recent exposure of chemotherapy in ovarian cancer: A systematic review and meta-analysis."
	
Sears, S., et al. (2022). "PUDENDAL BLOCK ANALGESIAWITH VAGINAL SURGERY: a RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL." Female Pelvic Medicine & Reconstructive Surgery 28(6): S135.
	Introduction: Effective opioid‐sparing postoperative analgesia often requires a multimodal approach, and regional nerve blocks may be one way to decrease opioid use following surgery. Objective: To determine whether a pudendal nerve block at the time of vaginal surgery is associated with improved postoperative pain control and decreased opioid consumption compared to a placebo sham injection in patients undergoing vaginal surgery. Methods: In this randomized, double‐blind, placebo controlled trial, we enrolled women undergoing benign vaginal surgery performed by three urogynecology providers at a single academic institution. Exclusion criteria included patients with a diagnosis of chronic pelvic pain, inability to receive non‐narcotic analgesia, or any concurrent abdominal procedure. Patients were randomized to receive a transvaginal bilateral pudendal nerve block (9 mL 0.25% bupivacaine +1 mL 40 mg/mL triamcinolone) or a sham injection (10 mL normal saline) at the conclusion of surgery while under anesthesia. Primary endpoints were visual analog pain scores (VAS) and postoperative opioid requirement, measured in the post‐anesthesia recovery unit (PACU) and on post‐operative days (POD) 1 and 4. A power calculation determined 60 patients were required to show a mean difference of 20 mm on a 100 mm VAS. Opioid administration was standardized as morphine milligram equivalents (MME). VAS scores and opioid usage were compared using Wilcoxon rank sum analysis. Results: We randomized 71 patients: 36 pudendal block and 35 sham injection. The study groups were well matched with no differences in baseline characteristics or type of surgery performed. Pelvic organ prolapse repairs were the most common procedures (n = 63, 87.5%). There was no difference in anesthetic dose or operative time between groups. Pain scores were equivalent between groups in the PACU (mean VAS 53.1 block vs 56.4 sham, P = 0.517) and on POD 4 (mean VAS 26.7 block vs 35.5 sham, P = 0.131). On POD 1, the intervention group did report less pain than the sham group (mean VAS 29.2 vs 42.5, P = 0.047). Patients who received a pudendal block took fewer opioid medications than those in the placebo group at all time points, but this difference did not meet statistical significance (PACU 5 vs 7.8 MME, POD1 7.5 vs 11.25 MME, POD4 7.5 vs 21.25 MME, all P > 0.05). Conclusions: Pudendal nerve blocks at the time of vaginal surgery help with pain control in the immediate postoperative period and may be an additional tool for non‐narcotic postoperative pain control.

Sebastian, D. S., et al. (2023). "Prevention of peritoneal adhesions after gynecological surgeries: A systematic review."
	
Second Affiliated, H., et al. (2022). Effect of Prednisone and Aspirin on IVF-ET Outcome Among Patients With Thyroid Autoimmunity.
	No Results Available Drug: Prednisone and Aspirin|Drug: Placebo clinical pregnancy rate Female Phase 4 540 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 2022-0513 December 31, 2026

Secord, A. A., et al. (2022). "FLORA-5/GOG3035: Frontline chemo-immunotherapy (paclitaxel-carboplatinoregovomab [PCO] versus chemotherapy (paclitaxel-carboplatin-placebo [PCP]) in patients with advanced epithelial ovarian cancer (EOC)-Phase III, double-blind, placebo-controlled, global, multinational study." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Oregovomab, a murine IgG1 monoclonal antibody, has high affinity binding to tumor associated antigen CA125, thus, rendering the target antigen CA125 more immunogenic or "neoantigen-like" through altered and enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when oregovomab is combined with chemotherapy. In a randomized phase II study, oregovomab in combination with paclitaxel and carboplatin (PC) induced tumor immunity and demonstrated significant improvement in median PFS (41.8 months(m) PCO vs 12.2m PC, HR 0.46, p=0.0027) and median OS (N.E. PCO vs 43.2 m PC, HR O.35, p=0.043) in patients with previously untreated EOC. Oregovomab combined with PC had a favorable toxicity profile. FLORA-5/GOG3035, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Method(s): The study is a phase 3, multicenter, double-blind, placebo-controlled trial. Optimally debulked patients with FIGO III/IV EOC and serum CA125 >= 50 U/ml receiving adjuvant (Cohort 1) or patients receiving neoadjuvant chemotherapy post-interval cytoreductive surgery (Cohort 2) will be randomized to PC + oregovomab or placebo (PCO vs. PCP). Patients with germline BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with an additional dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients will be administered oregovomab/placebo after debulking surgery at cycles 4 and 6 with two additional doses at 6- and 18-weeks following cycle 6 in Cohort 2. No other front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim futility analysis will be performed. Secondary objectives include OS, frequency and severity of AEs, and QoL. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of correlative biomarkers. The study is actively enrolling in the US, Canada, Belgium, Italy, Spain, Czech Republic, Hungary, Poland, Korea, Taiwan, Mexico, Argentina, and Chile. 179 patients were enrolled at time of submission.

Segev, Y., et al. (2020). "Is There a Survival Advantage in Diagnosing Endometrial Cancer in Asymptomatic Patients? A Systemic Review and Meta-analysis." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 42(4): 481.
	Data supporting a survival advantage of endometrial cancer diagnosed before the onset of postmenopausal bleeding are lacking. This study sought to compare overall survival and disease recurrence between women who were asymptomatic at diagnosis and women who were symptomatic at diagnosis. A systemic search was conducted in databases using the terms: "asymptomatic," "ultrasound," "screening," and "endometrial cancer." Only original research studies that compared characteristics of tumour advancement and survival measures were included. The six articles included in the meta-analysis comprised 2961 patients. Data were collected on study design and period, number and characteristics of participants, and outcomes in terms of tumour histology and survival measures. Higher rates of stage I tumours were shown among asymptomatic patients (relative risk 1.19). The proportion of high-grade histology did not differ between the two groups (relative risk 0.92). The crude pooled estimate for overall survival did not yield statistical significance, nor did recurrence-free survival (which was reported by three studies). In conclusion, endometrial cancer diagnosed in asymptomatic women is not associated with higher survival than in symptomatic women. Invasive procedures in asymptomatic women with incidental ultrasonographic findings should be carefully weighed because no survival advantage is expected. (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Sehar un, N., et al. (2024). "Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) Approach for infertility treatment outcomes."
	
Sehouli, J., et al. (2022). "Role of cytoreductive surgery for the second ovarian cancer relapse in patients previously treated with chemotherapy alone at first relapse: A subanalysis of the DESKTOP III trial." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: The DESKTOP III trial has demonstrated a significant survival benefit in AGO-score positive patients who underwent complete cytoreduction at 1st relapse compared to those treated with chemotherapy alone. The question whether eligible patients who missed the opportunity of potentially life prolonging surgery at 1st relapse would benefit from surgery at the time of their second relapse, remains open. Method(s): Patients randomized in the standard, non-surgical arm of the DESKTOP III trial who underwent cytoreductive surgery at a subsequent relapse at investigator's discretion were separately analyzed. Result(s): The median progression-free survival (PFS) counted from randomization of 201 patients in the control arm of DESKTOP III was 14.0 months. 171 (85%) had progressive or relapsing disease and 32 of 171 (19%) underwent cytoreductive surgery. Patients' median age at this subsequent surgery was 63 years (range: 46 - 78). Complete tumor resection was achieved in 19 patients (60%), while 5 (16%) had postoperative residual disease (n = 8 missing data). Sixteen patients (50%) commenced systemic treatment within 90 days from surgery, as documented. Thirty-and 90-day surgical mortality rates were 1 (3%) and 2 (6%), respectively. Within a postoperative median follow-up time of 43.8 months, 12 (38%) deaths were reported. Median overall survival after surgery (OS) was 54.0 months. One-and 2-year OS rates were 91% and 84%, respectively. Conclusion(s): Cytoreductive surgery for subsequent ovarian cancer relapse appears feasible and with low mortality in selected patients who received non-surgical treatment at 1st relapse despite a positive AGO-score. Surgery should be considered as an option in carefully selected patients also later in their journey within a specialized gynecological cancer setting.

Sehouli, J., et al. (2021). "Bevacizumab Combined with Platinum-Taxane Chemotherapy as First-Line Treatment for Advanced Ovarian Cancer: Results of the NOGGO Non-Interventional Study (OTILIA) in 824 Patients." Cancers 13(19).
	In the single-arm non-interventional OTILIA study, patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IV ovarian cancer received bevacizumab (15 mg/kg every 3 weeks for up to 15 months) and standard carboplatin-paclitaxel. The primary aim was to assess safety and progression-free survival (PFS). Subgroup analyses according to age were prespecified. The analysis population included 824 patients (453 aged <70 years, 371 aged ≥70 years). At data cutoff, the median bevacizumab duration was 13.8 months. Grade ≥3 adverse events (AEs), serious AEs, and AEs leading to bevacizumab discontinuation were more common in older than younger patients, whereas treatment-related AEs were less common. Median PFS was 19.4 months, with no clear difference according to age (20.0 vs. 19.3 months in patients <70 vs. ≥70 years, respectively). One-year OS rates were 92% and 90%, respectively. Mean change from baseline in global health status/quality of life showed a clinically meaningful increase over time. In German routine oncology practice, PFS and safety were similar to reported randomized phase 3 bevacizumab trials in more selected populations. There was no notable reduction in effectiveness and tolerability in patients aged ≥70 years; age alone should not preclude use of bevacizumab-containing therapy. ClinicalTrials.gov: NCT01697488.

Sehouli, J., et al. (2022). "NOGGO ov-42/MAMOC: Rucaparib MAintenance after Bevacizumab Maintenance following Carboplatin based first line chemotherapy in Ovarian Cancer patients." Oncology Research and Treatment 45(Supplement 3): 115.
	Background: Most ovarian cancer (OC) patients are diagnosed in advanced stages. Debulking surgery, followed by platinum-based chemotherapy and bevacizumab (bev), followed by bev maintenance therapy, is a therapeutical option for advanced BRCA wild type (BRCAwt) OC patients in Germany. Despite that 70% of the patients will relapse within 2 years after diagnosis, prolongation of maintenance therapy might be an option to improve PFS. Current data showed that bev given longer than 15 months do not translate in better PFS. Therefore, in this clinical trial we aim to analyze the role of sequential maintenance with bev followed by rucaparib vs bev alone in BRCAwt high grade OC patients. NOGGO Ov-42/MAMOC trial (NCT04227522) is a phase 3, randomized, placebo- controlled study evaluating rucaparib maintenance following bevacizumab maintenance for the treatment of advanced primary high grade BRCAwt OC. Method(s): 190 BRCA wt patients with histologically confirmed advanced (FIGO stage IIIA- IV of the 2014 FIGO classification) high grade serous or high grade endometrioid OC, fallopian tube cancer, primary peritoneal cancer or clear cell carcinoma of the ovary will be randomized 2:1 to receive either rucaparib 600mg BID or placebo as maintenance therapy following first line chemotherapy with 6 cycles of Carboplatin/Paclitaxel and at least 12 months of bev given together with chemotherapy and as maintenance. Randomization is stratified by surgery planned timepoint (neoadjuvant vs. adjuvant), surgical outcome (no residual tumor mass vs. residual tumor mass), response to chemotherapy + bev (CR/ NED vs. PR/SD) and study center. Treatment will continue for 24 months or until disease progression, unacceptable toxicity, or withdrawal, whatever occurs first. Primary endpoint is PFS per RECIST v1.1. Secondary endpoints are PFS2, quality of life (EORTC QLQ-C30/OV28, FSI, SF-12, PROC-CTCAE, Everyday Memory Questionnaire), daily activity, time to next medical intervention, time to next subsequent therapy, safety assessments and OS. At the moment 14 patients are randomized.

Seib, C., et al. (2022). "Improving health-related quality of life in women with breast, blood, and gynaecological Cancer with an eHealth-enabled 12-week lifestyle intervention: the women's wellness after Cancer program randomised controlled trial." BMC Cancer 22(1): 747.
	Background: The residual effects of cancer and its treatment can profoundly affect women's quality of life. This paper presents results from a multisite randomized controlled trial that evaluated the clinical benefits of an e-health enabled health promotion intervention (the Women's Wellness after Cancer Program or WWACP) on the health-related quality of life of women recovering from cancer treatment.; Methods: Overall, 351 women previously treated for breast, blood or gynaecological cancers were randomly allocated to the intervention (WWACP) or usual care arms. The WWACP comprised a structured 12-week program that included online coaching and an interactive iBook that targeted physical activity, healthy diet, stress and menopause management, sexual wellbeing, smoking cessation, alcohol intake and sleep hygiene. Data were collected via a self-completed electronic survey at baseline (t 0 ), 12 weeks (post-intervention, t 1 ) and 24 weeks (to assess sustained behaviour change, t 2 ). The primary outcome, health-related quality of life (HRQoL), was measured using the Short Form Health Survey (SF-36).; Results: Following the 12-week lifestyle program, intervention group participants reported statistically significant improvements in general health, bodily pain, vitality, and global physical and mental health scores. Improvements were also noted in the control group across several HRQoL domains, though the magnitude of change was less.; Conclusions: The WWACP was associated with improved HRQoL in women previously treated for blood, breast, and gynaecological cancers. Given how the synergy of different lifestyle factors influence health behaviour, interventions accounting for the reciprocity of multiple health behaviours like the WWACP, have real potential for immediate and sustainable change.; Trial Registration: The protocol for this randomised controlled trial was submitted to the Australian and New Zealand Clinical Trials Registry on 15/07/2014 and approved on 28/07/2014 ( ACTRN12614000800628 ). (© 2022. The Author(s).)

Seidler, S., et al. (2021). "Clinical Impact of Lymphadenectomy after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Review of Available Data." Journal of Clinical Medicine 10(2).
	Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter.

Seifalian, A., et al. (2022). "Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?" International Journal of Molecular Sciences 23(24).
	Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.

Seiiedi-Biarag, L., et al. (2020). "The effect of cognitive-behavioral therapy on psychological distress in the mothers of preterm infants: a systematic review and meta-analysis." Journal of Psychosomatic Obstetrics and Gynecology 41(3): 167-176.
	Introduction: The birth of a preterm infant has the potential to cause stress, anxiety, depression and Post-Traumatic Stress Disorder (PTSD) in mothers. Numerous interventions have been developed for the parents of preterm infants to deal with these problems. Cognitive-Behavioral Therapy (CBT) is a client-centered intervention for improving mental health and alleviating psychological distress by transforming unconstructive thoughts and behaviors. The present systematic review was conducted to evaluate the effect of CBT on anxiety, depression and PTSD (the primary outcomes) and stress (the secondary outcome) in the mothers of preterm infants. Method(s): A search was carried out of all the articles published by 30 Sep. 2018 in English and Persian databases including Medline (via PubMed), Scopus, Embase (via Ovid), Web of Science, Psycinfo, Google Scholar, SID, Magiran and Iran Medex. The risk of bias was assessed for the studies based on the Cochrane Handbook. The meta-analysis results were reported as Standardized Mean Difference (SMD). The heterogeneity of the studies was examined using I2, T2 and Chi2. Result(s): Four clinical trials on 455 mothers with preterm infants were systematically reviewed. The meta-analysis results revealed a lower mean depression score in the CBT group compared to the controls (SMD = -0.45; 95% CI: -0.98 to 0.08), but this difference was not statistically significant (p =.09). The mean scores of PTSD (MD = -11.69; 95% CI: -19.45 to -3.94; p =.003) and anxiety (SMD = -0.38; 95% CI: -0.61 to -0.15; p =.001) were significantly lower in the CBT group too. Conclusion(s): CBT was effective in decreasing the level of PTSD and anxiety in the mothers of preterm infants. Due to the small number of included studies and the small sample size, clinical trials with large sample sizes and a low risk of bias are recommended to provide evidence for the implementation of interventions affecting psychological distress in the mothers of preterm infants in clinical settings.Copyright © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Selcuk, A. K. and E. Yanikkerem (2021). "Effect of acupressure on primary dysmenorrhea: Review of experimental studies." JAMS Journal of Acupuncture and Meridian Studies 14(2): 33-49.
	Primary dysmenorrhea is defined as cramping pain in the lower abdomen with no pelvic diseases, and it has a high prevalence in many countries. Acupressure is a widely used complementary treatment method for primary dysmenorrhea. This review examined experimental studies to determine the effects of acupressure on primary dysmenorrhea using the databases PubMed, Google Scholar, and CINAHL with the keywords "Acupressure" and "Dysmenorrhea". There were 2227 records in the databases, and 330 articles were published between 1989 and March 2020. Experimental studies in the English language were reviewed according to the PRISMA guidelines. This review included 28 published studies that were assessed using the Jadad score for quality. The studies were categorized as studies of acupressure at the LR3 point (n = 4), at the SP6 point (n = 9), at auricular points (n = 5), at multiple points (n = 8), and with devices (n = 2). Moreover, studies of self-acupressure (n = 9) were identified. The studies demonstrated that acupressure could reduce menstrual symptoms, the severity and duration of menstrual pain, distress, and anxiety. Furthermore, it helped improve the quality of life and well-being of patients and provide psychological support and self-care. Acupressure is an inexpensive, easy-to-apply, and non-pharmacological treatment and is useful for reducing primary dysmenorrhea, and women can apply this method anywhere by themselves. However, high-quality randomized controlled trials with larger samples are necessary to establish the evidence for acupressure as an effective intervention .Copyright © 2021 Korean Pharmacopuncture Institute. All rights reserved.

Selickova, M. S. (2019). "Menopausal therapy: Modern view of the problem." Advances in gerontology = Uspekhi gerontologii 32(5): 732-736.
	The steady tendency of modernity improve the average life expectancy of a man dictates the necessity of implementing the anti-aging stratege, one of the stratege for women is menopausal therapy. Currently, the protective effect of menopausal therapy for cardiovascular system has been proven up to 60 years after it's implication in treatment. MHT is rarely used in Russia, largely due to the hormonophobia of patients and doctors especially with oncological risk. In contrary, recent studies indicate prolonged use of MHT decrease the risk of breast, ovarian, cervical and endometrial cancer. Morden microdosed medications that include dydrogesteron and progesterone as a progestational agent, also minimize the risk. Currently, there are no restictions on the duration of appucation. Total mortality decrease by 30% based on the result of meta-analysis 23 studies, which involve 39 049 people age until 60 years old with menopausal therapy.

Seligson, J. M., et al. (2021). "Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer." Annals of Pharmacotherapy 55(7): 921-931.
	Objective: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. Data Sources: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. Study Selection and Data Extraction: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. Data Synthesis: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). Relevance to Patient Care and Clinical Practice: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. Conclusion(s): Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.Copyright © The Author(s) 2020.

Sellers, R., et al. (2022). "The use of Embryoglue (EG) for embryo transfer does not improve live birth rates: a prospective randomized controlled trial." Reproductive Biomedicine Online 45(Supplement 1): e49.
	Background and Aim: Despite the advances in the in vitro fertilization (IVF) lab, there are not many strategies to improve embryo transfer (ET) success rate. One of these strategies is the use of special culture media that are specific for ET, like EG. This culture media is one of the most used for ET but its current evidence is scarcy and contradictory. Method(s): In order to elucidate this question we carried out a prospective randomized controlled trial since March 2018 to January 2019. We randomized all the donated oocyte cycles performing a fresh single embryo transfer (SET) on day 5. The randomization included a control and a study group (EG). Clinical parameters studied were implantation rate, clinical pregnancy rate, clinical miscarriage rate, live birth rate and newborn weights. We performed a first randomization with a total of 109 patients. Sixty one were included in the control group (GLOBAL TOTAL (GT), LifeGlobal) and 48 in the study group (EG). The second randomization included a total of 193 patients. Eighty nine were included in the control group (Continuous Single Culture Complete (CSCC), IrvineScientific) and 104 in the study group (EG). Patients that were diagnosed of repetitive implantation failure (RIF) were excluded. Result(s): In the first randomization we did not reach any statistically significant difference for implantation rate (60% vs. 54.2%, p=0.331), clinical pregnancy rate (60.7% vs. 54.2%, p=0.560), clinical miscarriage rate (8.2% vs. 12.5%, p=0.531), live birth rate (49.2% vs. 39.6%, p=0.339) or newborn weight (3234.3+/-459 vs. 3293+/-589.7, p=0.699) between GT and EG, respectively. In the second randomization we did not reach any statistically significant differences for implantation rate (57.3% vs. 63.5%, p=0.460), clinical pregnancy rate (48.3% vs. 56.7%, p=0.251), clinical miscarriage rate (18.6% vs. 13.1%, p=0.582), live birth rate (37.2% vs. 50.5%, p=0.078) or newborn weight (3326.1+/-584.6 vs. 3205.6+/-550.9, p=0.349) between CSCC and EG, respectively. Conclusion(s): We conclude that EG did not improve any of the clinical parameters studied in donated egg cycles. It is necessary to perform prospective randomized controlled trials in order to check if any difference could be reached between EG and other culture media for ET, as well as in other patient groups.Copyright © 2022

Sener, N. and F. University (2022). Insomnia and Mindfulness Stress Reduction Program.
	No Results Available Other: mindfulness stress reduction program women's health initiative insomnia scale|Menopause-Specific Quality of Life Scale Female Not Applicable 192 Other Allocation: Non-Randomized|Intervention Model: Single Group Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Supportive Care FIRAT UNIVERSTY January 29, 2023

Senguttuvan Rosemary, N., et al. (2023). "Impact of Sodium Thiosulfate on Prevention of Nephrotoxicities in HIPEC: An Ancillary Evaluation of Cisplatin-Induced Toxicities in Ovarian Cancer." Annals of Surgical Oncology 30(13): 8144-8155.
	Purpose: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary.; Methods: A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m 2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs.; Results: Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways.; Conclusions: ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered. (© 2023. The Author(s).)

Senior, S., et al. (2022). "Effective configuration of services for referral, risk assessment and risk management in familial ovarian cancer."
	
Senior, S., et al. (2023). "Clinical and cost effectiveness of assisted reproduction techniques for people with unexplained health-related fertility problems, mild endometriosis, and people with a single abnormal semen parameter."
	
Senior, S., et al. (2023). "Effectiveness of screening hysteroscopy (with or without treatment of any detected uterine cavity abnormalities) on reproductive outcomes for people with female factor fertility problems."
	
Senior, S., et al. (2023). "Likelihood of spontaneous conception when tubal catheterisation/cannulation is used for proximal tubal obstruction."
	
Şenışık, S., et al. (2022). "The effect of resistance exercise on quality of life and fatigue in patients with gynecological cancer." Spor hekimligi dergisi/turkish journal of sports medicine 57(1): 44‐50.
	
Senmao, Z. and Q. Xing (2022). "Maternal alcohol consumption and risk of postpartum depression: a meta-analysis of cohort studies."
	
Senocak, G. N. C. and E. P. T. Yilmaz (2022). "Can endometrial injury increase the success of clomiphene citrate in achieving pregnancy? Endometrial injury and clomiphene citrate." Annals of Clinical and Analytical Medicine 13(6): 688-692.
	Aim: The aim of the study is to observe whether endometrial injury has an effect on pregnancy success in patients who are scheduled for timed intercourse after ovulation induction with the use of clomiphene citrate in patients with unexplained infertility. Material(s) and Method(s): The study was planned as a prospective randomized controlled trial with 215 patients, 105 patients in the injury group and 110 patients in the control group. All patients had unexplained infertility. In the injury group, endometrial injury was performed, before the ovulation induction cycle, in the mid-luteal phase. No intervention was performed on the patients in the study group before the treatment cycle. Ovulation induction was initiated by administering 100 mg/day clomiphene citrate and after follicle development, human chorionic gonadotropin (hCG) was administered to the patients in both groups and timed intercourse (36 hours after hCG) was planned for all patients. Result(s): It was observed that 27 (25.7%) patients in the injury group and 19 (17.3%) patients in the control group could achieve pregnancy, 21 (20%) of these patients in the injury group and 14 (12.7%) patients in the control group were able to achieve clinical pregnancy. As a result, although both pregnancy and clinical pregnancy rates were found to be increased in the injury group, this increase was not statistically significant. Discussion(s): Much larger and more comprehensive studies are needed to show that adding endometrial injury to treatment with clomiphene citrate, which is an extremely cost-effective and easy procedure, can actually increase pregnancy rates.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Sensei, B., et al. (2023). A Study of SNS-101 (Anti VISTA) Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors.
	No Results Available Drug: SNS-101 (anti-VISTA)|Drug: Cemiplimab Adverse Events - Part A & B|Determine the Recommended Phase 2 dose or maximum tolerated dose - Part A & B|Objective Response Rate (ORR) - Part C|Determine pharmacokinetic profile (maximum concentration) of SNS-101 - Part A, B & C|Determine pharmacokinetic profile (area under the curve) of SNS-101 - Part A, B & C|Determine pharmacokinetic profile (total clearance) of SNS-101 - Part A, B & C|Determine pharmacokinetic profile (terminal half life) of SNS-101 - Part A, B & C|Number of participants with anti-SNS-101 antibodies post-administration of SNS-101 - Part A, B & C|Objective Response Rate (ORR) - Part A & B|Duration of Response (DoR) - Part A, B & C|Disease Control Rate (DCR) - Part A, B & C|Progression Free Survival - Part A, B and C|Adverse Events - Part C All Phase 1|Phase 2 169 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment SNS-101-2-1 June 2027

Seo, J.-M., et al. (2022). "Effectiveness of a Mobile Application for Postpartum Depression Self-Management: Evidence from a Randomised Controlled Trial in South Korea." Healthcare (Basel, Switzerland) 10(11).
	This study examined the effectiveness of the Happy Mother mobile app developed for self-management of postpartum depression, based on cognitive behavioural therapy. A randomized controlled trial, with a pre- and a post-test design, was conducted in South Korea. Effectiveness was analysed using repeated measures ANOVA and Wilcoxon Signed Rank Test. We confirmed that the experimental group performed significantly more health promoting behaviours than the control group (F = 5.15, p = 0.007). However, there was no significant difference in postpartum depression, knowledge of depression, maladaptive beliefs, social support, sleep quality, and stress-coping behaviours between the two groups. The experimental group's mood score increased by 1.79 ± 2.51 points, resulting in significant differences before and after the intervention (Z = -2.81, p = 0.005). The quality of sleep score in the experimental group increased by 1.48 ± 1.70 points and was also significantly different after the intervention (Z = -3.23, p = 0.001). The activity practice rate of the experimental group significantly increased by 30.27 ± 29.27% after using the app (Z = -2.81, p = 0.005). We found the app to be effective in promoting mothers' health behaviour and improving their depressive mood.

Sepahi, S., et al. (2023). "A systematic review of emerging technologies to enhance the treatment of ovarian cancer." Pharmaceutical development and technology 28(7): 660-677.
	The efficacy and safety of chemotherapy are two major challenges when it comes to treating ovarian cancer. The associated undesirable side effects of chemotherapy agents jeopardize the clinical intent and the efficiency of the therapy. Multiple studies have been published describing new developments and novel strategies utilizing the latest therapeutic and drug delivery technologies to address the efficacy and safety of chemotherapeutics in ovarian cancers. We have identified five novel technologies that are available and, if used, have the potential to mitigate the above-mentioned challenges. Nanocarriers in different forms (Nano-gel, Aptamer, peptide medicated formulations, Antibody-drug conjugation, surface charge, and nanovesicle technologies) are developed and available to be employed to target the cancerous tissue. These strategies are promising to improve clinical efficacy and reduce side effects. We have systematically searched and analyzed published data, as well as the authors intent for the described technology on each publication. We narrowed to 81 key articles and extracted their data to be discussed in this review. In summary, the selected articles investigated the pharmacokinetic properties of drugs combined with nanocarriers and found significant improvement in efficacy and safety by reducing the IC50 values and drug doses. These key papers described promising novel technologies in anti-cancer therapeutic approaches to enable sustained drug release and achieve prolonged drug performance near the tumor site or target tissue.

Serafino, P., et al. (2023). "Surgical adhesions after laparoscopic myomectomy: methods of prevention." Italian Journal of Gynaecology and Obstetrics 35(1): 120-130.
	Objective. Adhesions are one of the most common complications of myomec-tomy and subsequent surgical procedures. Laparoscopic myomectomy is a low-risk procedure, with an adhesion rate of 50%, unlike laparotomy which has increased rates of 94%. The primary consequences of postoperative ad-hesions are chronic pelvic pain and female infertility. This narrative review is conducted to report the evidence on methods to reduce adhesions after laparoscopic myomectomy. Materials and Methods. An electronic database search (PubMed, Medline and Embase) was performed up to April 2022. A search algorithm was de-veloped incorporating the terms "myomectomy", "adhesions", "laparosco-py", "infertility", "anti-adhesion agents". Results. The incidence of adhesions after laparoscopic myomectomy without adhesion barriers is variable, between 23% and 88%. The variability in adhe-sions' onset is due to tissue trauma, the incision location and length, number of knots or kind of suture material and the experience of the surgeon, but also the use of anti-adhesion agents. The icodextrin 4% and the auto-crosslinked hyaluronic acid solution gel showed a significant decrease in the incidence and severity of adhesions in intervention groups. The polyethylene glycol amine plus dextran aldehyde polymers reported a decrease in the total adhesion score at second-look surgery after laparoscopic myomectomy. Oxidized regenerated cellulose showed efficacy in prevention of adhesions after laparoscopic myomectomy. Conclusions. Laparoscopic myomectomy reduces the risk of new adhesion formation but do not eliminate it entirely. Oxidized regenerated cellulose, au-to-crosslinked hyaluronic acid gel among natural materials, and polyethylene glycol amine plus dextran aldehyde polymers among synthetic materials, decrease the incidence of adhesions.Copyright © 2023, EDRA S.p.A. All rights reserved.

Serati, M. and A. Braga (2023). "Re: CO2 Surgical Laser for Treatment of Stress Urinary Incontinence in Women: A Randomized Controlled Trial." European Urology 83(4): 373.
	
Serati, M., et al. (2022). "Up-to-Date Procedures in Female Stress Urinary Incontinence Surgery: A Concise Review on Bulking Agents Procedures." Medicina (Kaunas, Lithuania) 58(6).
	To avoid complications related to mid-urethral slings (MUS), alternative procedures to treat stress urinary incontinence (SUI), such as urethral bulking agents (UBAs) have been adopted. The aim of this review is to narratively report the efficacy and safety of UBAs for SUI treatment. For this review, research from PubMed and EMBASE was performed to evaluate relevant studies that were undertaken from January 2012 to January 2022. Nineteen prospective studies were included. Several definitions of subjective and objective success were adopted. At a follow-up of <24 months, significant improvement was widely observed, even if with a heterogeneous rate of success between 32.7-90%, and a reinjection rate of 8.3-77.3%. Compared with other procedures, MUS resulted as significantly superior to UBAs but was balanced by a higher complication rate. Acute urinary retention, urinary tract infection and de novo urgency, and other complications, such as injection site rupture, urethral erosion and particle migration have been described after UBAs. SUI after UBAs treatment resulted in improvements in all studies and can be considered a safe and effective option to treat SUI. However, homogenous and longer-term data lack, limiting general recommendations. Thus, larger RCTs evaluating long-term effects are required.

Serati, M., et al. (2019). "The role of urodynamics in the management of female stress urinary incontinence." Neurourology and Urodynamics 38(S4): S42-S50.
	Aim: The role of urodynamic study (UDS) in the management of female stress urinary incontinence (SUI) is one of the most controversial and debated topic in urogynecology. Here, we aimed to systematically assess the most relevant available evidence on urodynamics' value in the management of women with stress urinary incontinence. Method(s): A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was performed in May 2018. Only randomized clinical trials, prospective studies, or retrospective studies articles evaluating the use of urodynamic studies in women with stress urinary incontinence were included. Result(s): After screening a total of 3055 records, 39 studies published from 1996 to 2018 were included. Conclusion(s): In an uncomplicated population of women with SUI, it is not demonstrated that preoperative urodynamic evaluation can improve the outcome of continence surgery; however, UDS provides additional information regarding lower urinary tract function that could guide the physician to make the right therapeutic choice. UDS should be considered mandatory before surgery in complicated patients, but its use should also be evaluated in index patients when the results may help counseling and management of these women.Copyright © 2018 Wiley Periodicals, Inc.

Serdinsek, T., et al. (2021). "Is the fixation of single incision TVT-S tape as good as that of transobturator tape? An ultrasound study of randomized trial results." International Urogynecology Journal 32(1): 141‐148.
	Introduction: TVT‐Secur (TVT‐S) was the first single‐incision sling available on the market and was soon found to have less efficacy than mid‐urethral slings. Our aim was to assess the position and tape descent following TVT‐O and TVT‐S H in a U procedure and, based on this evaluation, to find the possible reason for lower TVT‐S surgery efficacy. Methods: We conducted an ultrasound study of a randomised trial with a 3‐year follow‐up that took place between 2007 and 2009 and included 197 women with urodynamic stress urinary incontinence. Of these, 67 were allocated to receive the TVT‐O procedure, 64 to TVT‐S in the H position, and 65 in the U position. Patients underwent a complete urogynaecological and ultrasound examination. The positions of the bladder neck and the tape after surgery were assessed and the data obtained compared between groups. Results: Our primary study showed a significantly higher rate of positive stress tests in the TVT‐S groups compared to the TVT‐O group. After surgery, there was no difference between the position of the tape at rest and at maximal Valsalva between the groups. In TVT‐O patients, the mean length of the upper tape margin descent increased from 6 mm on the 1st day after surgery to 9 mm 3 months after surgery and remained stable afterwards. For TVT‐S patients, there was a further increase of up to 15 mm in tape descent after 3 months. Conclusions: Our results show that the lower efficacy of TVT‐S might be due to inadequate fixation and increasing tape descent.

Serra, D., et al. (2023). "Acupuncture Reduces Severity of Hot Flashes in Breast Cancer: A Randomized Single-Blind Trial." Holistic Nursing Practice 37(6): 330-336.
	This study evaluated the effectiveness of traditional Chinese medicine-based therapeutic acupuncture (TA) in reducing the severity of hot flashes (HFs) in breast cancer patients and compared the effectiveness of TA to "sham" placebo acupuncture (SA). Subjects experiencing more than 10 episodes of HF/week were randomly assigned to TA or SA. The response was assessed by the Menopause-specific Quality of Life (MenQoL) scale, scoring the subject's perception of the severity of HFs. HFs were scored at baseline, after treatment, and 1-month follow-up. A total of 54 subjects enrolled (28 TA and 26 SA). Seven women withdrew from the study. A hot flash diary documented the number of HFs a subject experienced. Analysis included 47 subjects (27 TA and 20 SA). A statistically significant response in HF scores was noted in the TA group compared with the SA group (P = .0064.) On average HF scores dropped by 1.89 with TA, and only 0.16 with SA. At follow-up, TA subjects had a sustained response. TA is effective in reducing the intensity and severity of HF. With SA, no relative response/change in HF scores was noted. Larger studies and longer follow-up to assess durability of response to TA are needed. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Sevim, A., et al. (2021). "Cognitive Behavioral Treatment of Genital Pain: A Systematic Review."
	
Sfakianoudis, K., et al. (2020). "Novel Approaches in Addressing Ovarian Insufficiency in 2019: Are We There Yet?" Cell Transplantation 29.
	Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian insufficiency include premature ovarian failure (POF), poor ovarian response (POR), and advanced maternal age (AMA). Patient heterogeneity in the era of individualized medicine drives research forward leading to the emergence of novel approaches. This plethora of innovative treatments in the service of adequately managing ovarian insufficiency is called to undertake the challenge of addressing infertile patients exploring their reproductive options. This review provides an all-inclusive presentation and critical analysis on novel treatments that have not achieved routine clinical practice status yet, but have recently emerged as promising. In light of the lack of randomized controlled trials conveying safety and efficiency, clinicians are left puzzled in addressing the "how" and "for whom" these approaches may be beneficial. From ovarian injection employing platelet-rich plasma (PRP) or stem cells to artificial gametes and ovaries, ovarian transplantation, and mitochondrial replacement therapy, this descriptive review provides insight toward assisting the practitioner in decision making regarding these cutting-edge treatments. Biological mechanisms, invasiveness levels, efficiency, as well as possible complications, the current status along with bioethical concerns are discussed in the context of identifying future optimal treatment.Copyright © The Author(s) 2020.

Sforzini, L., et al. (2019). "Inflammation in cancer and depression: a starring role for the kynurenine pathway." Psychopharmacology 236(10): 2997-3011.
	Depression is a common comorbidity in cancer cases, but this is not only due to the emotional distress of having a life-threatening disease. A common biological mechanism, involving a dysregulated immune system, seems to underpin this comorbidity. In particular, the activation of the kynurenine pathway of tryptophan degradation due to inflammation may play a key role in the development and persistence of both diseases. As a consequence, targeting enzymes involved in this pathway offers a unique opportunity to develop new strategies to treat cancer and depression at once. In this work, we provide a systematic review of the evidence up to date on the kynurenine pathway role in linking depression and cancer and on clinical implications of this evidence. In particular, complications due to chemotherapy are discussed, as well as the potential antidepressant efficacy of novel immunotherapies for cancer.Copyright © 2019, The Author(s).

Sha, Y. and L. Huapeng (2021). "An indirect comparison meta-analysis of Noninvasive Intravesical Instillation And Intravesical Injection of botulinum Toxin-A for Overactive Bladder and Interstitial Cystitis/Bladder Pain Syndrome."
	
Shabani, F., et al. (2024). "The Effect of Rosa Foetida Extract along with Self-Care Education on Primary Dysmenorrhea: A Prospective Randomized Clinical Trial." Clinical and Experimental Obstetrics and Gynecology 51(1): ceog5101016.
	Background: Dysmenorrhea is among the most common conditions among young women. Herbal medicine is one of the alternative ways to treat dysmenorrhea. The purpose of this study was to determine the effect of Rosa Foetida extract along with self-care behaviors on primary dysmenorrhea. Method(s): A randomized clinical trial was conducted on 135 students residing in dormitories. The subjects were aged 18 to 24 years and unmarried. They divided into three groups of 45. The students received self-care behavior training on dysmenorrhea. After the training, two of the three groups received medications; one with Rosa Foetida extract and another with placebo capsules. The physical appearance of the capsules was similar. The third group received no medication. Data were collected through questionnaires including demographic characteristics questionnaire, a visual analogue scale (VAS), menstrual distress scale questionnaire (MDQ), dysmenorrhea self-care behaviors scale questionnaire (DSCS), and Pictorial Blood Loss Assessment Chart (PBAC). Repeated measurement of analysis of variance (ANOVA) was performed using SPSS software version 22 (IBM Corp., Armonk, NY, USA) to determine and compare the effects of interventions on menstrual pain and distress severity. Result(s): Comparison of the mean pain intensity before and after intervention implied a reduction in pain; especially in the Rosa Foetida extract group (p < 0.001). Menstrual distress also showed reduction which was greater in the case of the Rosa Foetida group. In addition to those, the reduction of menstrual bleeding was statistically significant in the Rosa Foetida group (p = 0.041). Conclusion(s): The results showed Rosa Foetida extract prescription, along with self-care behavior education did not have a positive effect on primary dysmenorrhea; however, it was seen to be effective on reducing menstrual distress.Copyright © 2024 The Author(s).

Shabani, F., et al. (2022). "The effects of Rosa foetida extract along with self-care education on primary dysmenorrhea: study protocol for a randomized clinical trial." Trials 23(1): 637.
	Background: Dysmenorrhea is one of the most common disorders among young women. Medicinal herbs are one of the alternative methods for the treatment of dysmenorrhea. This study will investigate the effect of Rosa foetida extract, along with self-care behavior education on primary dysmenorrhea among female students of Babol University of medical sciences.; Methods/design: A randomized clinical trial will be performed on single students, aged 18 to 24 years. The research samples will be divided into three groups. The students will receive self-care behavior education on dysmenorrhea. Following the education, two of the groups will receive Rosa foetida extract capsules and placebo capsules in two consecutive cycles every 8 h for two successive days, respectively. The capsules will have similar physical appearance. The third group will not receive any medication. Data will be collected through demographic characteristic questionnaire, visual analog scale, dysmenorrhea self-care behaviors scale questionnaire, pictorial chart, and menstrual distress scale questionnaire. In order to determine and compare the effect of pharmacological and educational interventions on the severity of dysmenorrhea in groups, an ANOVA analysis of variance test with repeated measures will be used by SPSS software version 22.; Discussion: The results will show the effects of Rosa foetida extract along with self-care behavior education on primary dysmenorrhea, and beneficial effects that may be found in the trial of this plant may be of use for women with the same problem.; Ethics and Dissemination: The study is approved by the Ethics Committee of Babol University of Medical Sciences (IR.MUBABOL.REC.1397.059).; Trial Registration: IRCT 20190318043086N1. Registered on 14 June 2019. (© 2022. The Author(s).)

Shabanian, B., et al. (2024). "Effects of Curcuma longa (turmeric) and curcumin on the premenstrual syndrome and dysmenorrhea: A systematic review." Journal of Endometriosis and Pelvic Pain Disorders.
	Premenstrual syndrome (PMS) and dysmenorrhea, in addition to harming the physical and mental health of women, also disrupt their daily life and quality of life. We aimed to investigate the effects and underlying mechanisms of Curcuma longa (turmeric) and curcumin on PMS and dysmenorrhea. PRISMA guideline 2020 was followed for conducting this systematic review. Comprehensive literature searches were conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Scopus. Finally, 17 articles were found after considering the study's inclusion and exclusion criteria into account. Data were extracted and entered into an Excel file for further investigation and drew the results. Curcuma longa and curcumin affect PMS and dysmenorrhea through various mechanisms. They inhibit the activity of cyclooxygenase-2 (COX-2) and the production of prostaglandins, thus reducing inflammation and pain. Additionally, curcumin's antioxidant properties protect against oxidative stress, and lipid peroxidation helps maintain hormonal balance, exert analgesic effects, and relieve the symptoms of PMS and dysmenorrhea. They also insert neurotransmitter modulatory properties, such as increased serotonin and dopamine levels, which may contribute to their antidepressant, and sedative effects. Curcuma longa and curcumin indicated promising therapeutic effects in reducing PMS and dysmenorrhea symptoms due to their anti-inflammatory and antioxidant effects. Although, further well-designed clinical trials are needed to establish their efficacy and optimal dosage.Copyright © The Author(s) 2024.

Shafierizi, S., et al. (2023). "Therapist-guided internet-based cognitive behavioral therapy versus face-to-face CBT for depression/anxiety symptoms in infertile women with adjustment disorders: A randomized controlled trial." Psychotherapy research : journal of the Society for Psychotherapy Research 33(6): 803-819.
	The present study compared the effectiveness of ICBT to face-to-face CBT on the improvement of adjustment disorder symptoms in infertile women. Method: In a pragmatic, multi-center (public or private), single-blinded, non-inferior randomized controlled trial (RCT), 152 patients with AD (100 women in public center and 52 women in private canter) were assigned to ICBT and CBT. Primary outcomes were Adjustment Disorder New Module-20 (ADNM-20) and Hospital Anxiety and Depression (HADS). Secondary outcomes were the Fertility Problem Inventory (FPI) and Fertility Adjustment Scale (FAS). Results: "Peaceful mind" ICBT was feasible and accessible for delivering the treatment to infertile women with AD. At end-of-treatment, improvements in ICBT were non-inferior to CBT for symptoms of AD, anxiety, and depression. Additionally, the non-inferiority of ICBT to CBT was maintained at a three-month follow-up. Conclusions: ICBT was non-inferior to CBT in improving mental symptoms in infertile women with AD.

Shah, A., et al. (2021). "Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS." The Journal of Clinical Endocrinology and Metabolism 106(1): 108-119.
	OBJECTIVE: To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic). DESIGN: Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29). MATERIALS AND METHODS: Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes. RESULTS: Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001). CONCLUSIONS: In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.

Shah, M., et al. (2022). "Effect of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a high-sugar meal breakfast the following day in postmenopausal women: a randomized cross-over study." Journal of sports sciences 40(2): 175‐184.
	High‐sugar consumption is related to dyslipidemia. How acute exercise affects postprandial lipid and lipoprotein particle responses to a high‐sugar meal (HSM) in postmenopausal women is unclear. We examined the effects of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a HSM breakfast the following day in 22 postmenopausal women. Subjects underwent exercise (EX) and no exercise (NE) conditions in the evening 13‐16�h before the HSM breakfast consumption, in a random order. During the EX condition, subjects performed supervised aerobic exercise for 60�min at 75% of age‐predicted maximum heart rate. The HSM (75.6% carbohydrate and 33% energy needs) was consumed after a 12‐h fast. Serum lipids and lipoproteins were assessed at baseline and postprandially (60, 120, 180�min). Repeated measures analysis showed significantly lower area under the curve (geometric means [95% CI]) for triglycerides (TG) (2.96[2.43, 3.61] vs. 3.24[2.70, 3.88] mmol/L*hr; p =�0.049) and very low density lipoprotein particles (VLDLP) (114.6[88.2, 148.9] vs. 134.3[108.1, 166.9] nmol/L*hr; p =�0.02) during the EX versus NE condition. There were no condition effects for other variables. In conclusion, the EX versus NE condition lowered postprandial AUC for TG and VLDLP following HSM consumption in postmenopausal women.Trial Registration: ClinicalTrials.gov Identifier: NCT02919488.

Shah, N., et al. (2021). "What happens after randomised controlled trials? Uterine fibroids and ulipristal acetate: systematic review and meta-analysis of "real-world" data." Archives of Gynecology and Obstetrics 303(5): 1121-1130.
	Purpose: "Real-world" data incorporates studies performed outside of controlled environments, allowing for a better understanding of the effects of treatment in routine clinical practice. We, therefore, performed a systematic review to summarise available "real-world studies" reporting on the use of ulipristal acetate (UPA) for management of uterine fibroids.; Methods: We designed a prospective protocol according to PRISMA guidelines and registered it with PROSPERO (ID: CRD42019151393). We searched all major databases for relevant citations until 20th September 2019. Our screen included studies for risk of bias using an adapted structured quality assessment tool. Random-effects meta-analysis was used to calculate proportion estimates for each outcome including 95% confidence interval. Reported heterogeneity was assessed using I 2 .; Results: Initial search yielded 755 studies and 13 were included in the final synthesis. Administration of UPA resulted in reduction in the size of fibroids in 56.5% of women, improved menorrhagia in 83% of women, improved perception of pain in 80.1% of women and lead to an improvement in global symptom scores in 85.2% of women. Mean reduction in surgical blood loss and surgical time with use of UPA was 59.85 ml and 12.47 min, respectively. Qualitative analysis suggested that there was no difference in overall surgical experience for patients treated with UPA compared to those without pre-treatment.; Conclusions: Our findings are consistent with previously reported data that UPA is an acceptable management option for women with fibroids. However, it provides limited benefits when used as a pre-operative adjunct, in terms of blood loss and surgical time.

Shaheen, U., et al. (2021). "Manual vacuum aspiration (m.v.a) versus conventional evacuation and curettage in early pregnancy loss." Pakistan journal of medical and health sciences 15(8): 2213‐2215.
	Objective: The aim of this study is to compare the efficacy of manual vacuum aspiration and conventional evacuation and curettage in early pregnancy loss Study Design: Randomized control trial Place and Duration: Study was conducted at department of obstetrics and gynecology Lady Reading Hospital Peshawar from 1st January 2019 to 31st August 2020. Methods Patients were early pregnancy loss (12 weeks or lesser gestational age) were enrolled. Patients were divided into two groups by lottery method. Group A were the patients who had conventional evacuation and curettage treatment. Group B were patient in which MVA was used. Patients' demographics were recorded after taking written consent. Gestational age was calculated from first day of last menstrual cycle and by ultrasound. Cervical ripening was done by (misoprostol 400mcg) two hours before procedure. Procedure was carried out under aseptic measures. Complete uterine evacuation by either procedure was assessed by ultrasound after procedure and complications were noted. Data was analyzed by SPSS 24.0. Results: Mean age in Group A was 29 years with SD ± 8.65 while mean age in Group B mean age was 30 years with SD ±7.62. Group B (Manual Vacuum Aspiration) was effective in 96% patients while Group A(Conventional Evacuation and Curettage) was effective in 89% patients. Complications were fewer in MVA as compared to conventional evacuation and curettage.

Shahmohammadi, A., et al. (2019). "The efficacy of herbal medicines on anxiety and depression in peri- and postmenopausal women: A systematic review and meta-analysis." Post Reproductive Health 25(3): 131-141.
	
Shahmoradi, S., et al. (2024). "The Effect of Magnesium Supplementation on Insulin Resistance and Metabolic Profiles in Women with Polycystic Ovary Syndrome: a Randomized Clinical Trial." Biological trace element research 202(3): 941-946.
	Due to the definitive known effect of magnesium on insulin resistance and the fact that insulin resistance is a main etiology in polycystic ovary syndrome (PCOS), it is assumed the use of magnesium supplements can improve insulin resistance, lipid profiles, and glucose and thus may also play a role in improving the clinical condition of patients with PCOS. We aimed to assess the effects of magnesium supplements on anthropometric, clinical, and metabolic parameters in women suffering from PCOS. This triple-blind randomized clinical trial study was conducted on women aged 15-35 years with PCOS. The patients were randomly assigned to receive a magnesium oxide supplement (250 mg/day for 2 months) or a placebo. The study parameters were evaluated and compared between two groups before as well as 2 months and 5 months after the initial assessment. In total, 40 cases (20 in each group) were recruited in the study. A significant reduction in the serum insulin level (P-value = 0.036) and insulin resistance (p-value = 0.032) was observed in the case group. Prescribing magnesium supplements could also lead to lowering total cholesterol, low-density lipoprotein, and fasting blood sugar along with increasing the level of high-density lipoprotein. We could not find any significant difference in anthropometric parameters as well as the mean systolic and diastolic blood pressures before and after intervention between the two groups. Although the rate of oligomenorrhea significantly decreased in the two study groups, it was no different across the two groups before and also after the intervention. The use of magnesium supplements in patients with PCO, regardless of the etiology or progression of the disease, can greatly improve the metabolic status of these patients by improving insulin resistance and modulating the level of lipid profile.Copyright © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Shahrahmani, H., et al. (2021). "Effect of fennel on primary dysmenorrhea: a systematic review and meta-analysis." Journal of complementary & integrative medicine 18(2): 261-269.
	Background: One of the most common complaints for women is dysmenorrhea. Several studies investigated the treatment effects of medicinal plants on primary dysmenorrhea.; Objectives: This systematic review and meta-analysis investigates the effect of Foeniculum vulgare (Fennel) on pain in primary dysmenorrhea in comparison to non-steroidal anti-inflammatory drugs such as mefenamic acid.; Methods: PubMed, EMBASE, EBSCO Web of Science, Scopus, Cochrane library, Cochrane Central Register of Controlled Trials (CENTRAL), Science Direct, ProQuest, ISI Web of Science, Google Scholar, Magiran, SID, Iran Medex, and Irandoc were searched up to January 2019. Quality assessment of clinical trials was conducted using Jadad scoring system. Totally, 12 studies were entered in the meta-analysis. I 2 was calculated to determine heterogeneity. Fixed effects and/or random effects models were applied.; Results: Meta-analysis of these trials showed that F. vulgare intake decreased significantly the intensity of dysmenorrhea compared to the placebo (SMD -0.632; CI: -0.827 to -0.436; p<0.001; heterogeneity p=0.807; I 2 =0%; fixed effect model; seven articles). However, the effect of Mefenamic acid with F. vulgare was not different from each other (SMD=-0.214; CI: -0.446 to 0.017; p=0.07; heterogeneity p=0.58; I 2 =0%; fixed effect model; six trials).; Conclusion: The F. vulgare alleviates dysmenorrhea. Regarding the same effect of F. vulgare with NSAIDs, it is highly recommend to the women suffered from dysmenorrhea specifically the ones who have high tendency toward herbal medicine. (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Shahveghar, A., et al. (2023). "The effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysis." The British Journal of Nutrition 130(2): 202-210.
	Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases characterised by unusual levels of sex hormones and dysfunction of the ovaries. The infertility rate is high among patients with PCOS. Unusual hormonal status can lead to the inability of ovaries to release functional and mature follicles. Clinical trials on the effects of N-acetylcysteine (NAC) supplementation on ovulation and sex hormones profile in women with PCOS have been controversial. We performed a systematic review and meta-analysis to evaluate the potential effects of NAC supplementation on ovulation and sex hormones profile. PubMed, Scopus, Embase, Web of Science and Cochrane Central library international databases were searched till September 2021. Meta-analysis was performed using a random-effects approach in case of significant between-study heterogeneity. Eighteen studies, including 2185 participants, were included in the present meta-analysis. NAC significantly reduced total testosterone (TT) levels (standardised mean difference (SMD): −0·25 ng/ml; 95 % CI (−0·39, −0·10); ‘ P < 0·001’, I 2 = 53·9 %, P = 0·034) and increased follicle-stimulating hormone (FSH) levels (SMD: 0·39 mg/ml; 95 % CI (0·07, 0·71); P = 0·01, I 2 = 70·9 %, P = 0·002). Oestrogen levels also increased after correcting publication bias. However, no significant effect was observed on the number of follicles, endometrial thickness, progesterone, serum luteinising hormone levels and sex hormone-binding globulin. The results indicated that NAC supplementation decreased TT levels and increased FSH levels. Overall, NAC supplementation might be effective in the improvement of reproductive system function in patients with PCOS.

Shailja, V. and P. Neelam (2022). "Role of laparoscopy in the management of cervical endometriosis following cervical biopsy: a systematic review."
	
Shaji, S., et al. (2021). "Perioperative NSAIDs and Long-Term Outcomes After cancer Surgery: a Systematic Review and Meta-analysis." Current oncology reports 23(12): 146.
	Purpose of Review: This review investigated the use of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) and long-term outcomes in cancer surgery patients, and whether this is dependent on cancer type, type of NSAID and timing of administration.; Findings: Perioperative NSAID use was found to be associated with longer disease-free survival (hazard ration, HR = 0.84 (95% CI, 0.73-0.97)) and overall survival (HR = 0.78 (95% CI, 0.64-0.94)). No difference was found between different types of NSAID for disease-free survival, although in overall survival ketorolac use was significant (HR = 0.63 (95% CI, 0.42-0.95)). Analysis on the timing of NSAID administration found no subgroup to be associated with cancer outcomes. The cancer-type analysis found an association with outcomes in breast and ovarian cancers. However, the level of certainty remains very low, mostly due to the heterogeneity and the retrospective nature of most studies. Perioperative NSAID use may be associated with increased disease-free and overall survival after cancer surgery. This may be dependent on the type of cancer and type of NSAID, and further research is needed to support this. These data may inform future prospective trials, which are needed to determine the clinical impact, as well as optimal NSAID regimen. (© 2021. The Author(s).)

Shallwani, S. M., et al. (2021). "Feasibility of a Pilot Randomized Controlled Trial Examining a Multidimensional Intervention in Women with Gynecological Cancer at Risk of Lymphedema." Current oncology (Toronto, Ont.) 28(1): 455-470.
	There is limited knowledge on non-invasive lymphedema risk-reduction strategies for women with gynecological cancer. Understanding factors influencing the feasibility of randomized controlled trials (RCTs) can guide future research. Our objectives are to report on the design and feasibility of a pilot RCT examining a tailored multidimensional intervention in women treated for gynecological cancer at risk of lymphedema and to explore the preliminary effectiveness of the intervention on lymphedema incidence at 12 months. In this pilot single-blinded, parallel-group, multi-centre RCT, women with newly diagnosed gynecological cancer were randomized to receive post-operative compression stockings and individualized exercise education (intervention group: IG) or education on lymphedema risk-reduction alone (control group: CG). Rates of recruitment, retention and assessment completion were recorded. Intervention safety and feasibility were tracked by monitoring adverse events and adherence. Clinical outcomes were evaluated over 12 months: presence of lymphedema, circumferential and volume measures, body composition and quality of life. Fifty-one women were recruited and 36 received the assigned intervention. Rates of recruitment and 12-month retention were 47% and 78%, respectively. Two participants experienced post-operative cellulitis, prior to intervention delivery. At three and six months post-operatively, 67% and 63% of the IG used compression ≥42 h/week, while 56% engaged in ≥150 weekly minutes of moderate-vigorous exercise. The cumulative incidence of lymphedema at 12 months was 31% in the CG and 31.9% in the IG (p = 0.88). In affected participants, lymphedema developed after a median time of 3.2 months (range, 2.7-5.9) in the CG vs. 8.8 months (range, 2.9-11.8) in the IG. Conducting research trials exploring lymphedema risk-reduction strategies in gynecological cancer is feasible but challenging. A tailored intervention of compression and exercise is safe and feasible in this population and may delay the onset of lymphedema. Further research is warranted to establish the role of these strategies in reducing the risk of lymphedema for the gynecological cancer population.

Shalma Noran, M., et al. (2023). "The efficacy of intrauterine infusion of platelet rich plasma in women undergoing assisted reproduction: a systematic review and meta-analysis." BMC Pregnancy and Childbirth 23(1): 843.
	Background: Platelet-rich plasma (PRP) is an autologous platelet concentration recently used in the reproductive field. Studies had conflicting results regarding its effect on pregnancy outcomes. We aimed to solve the debate on the safety and efficacy of PRP in women undergoing assisted reproduction and assess the influence of covariates on the outcomes of PRP infusion.; Methods: We searched PubMed, Scopus, Cochrane, and Web of Science in May 2023. We included randomized and non-randomized clinical trials as well as cohort studies assessing intrauterine PRP in sub fertile women undergoing assisted reproduction (IVF/ICSI). For the quality assessment, We used the Cochrane Risk of Bias Tool 1, the ROBINS-I tool, and the Newcastle-Ottawa Scale. We pooled the data using RevMan version 5.4.; Results: The data from 23 studies were pooled. PRP had favorable outcomes compared with the control group on clinical pregnancy rate (RR: 1.84, 95% CI 1.62 to 2.09; P < 0.00001), live birth rate (RR: 1.75, 95% CI: 1.24 to 2.47; P = 0.001), and miscarriages (RR: 0.51, 95% CI: 0.36 to 0.72; P = 0.0002). Women with repeated implantation failure had a significantly improved clinical pregnancy rate (RR: 1.83, 95% CI: 1.49 to 2.24; P < 0.00001), live birth rate (RR:1.83, 95% CI: 1.33 to 2.51; P = 0.002), and miscarriage rate (RR: 0.46, 95% CI: 0.31 to 068; P = 0.0001).; Conclusion: PRP showed promising results in assisted reproductive techniques. Further large and multicenter RCTs are required to compare the doses of PRP while identifying the specific population with the most benefits from PRP. (© 2023. The Author(s).)

Shamasbi Sevda, G., et al. (2020). "The effect of probiotics, prebiotics, and synbiotics on hormonal and inflammatory indices in women with polycystic ovary syndrome: a systematic review and meta-analysis." European journal of nutrition 59(2): 433-450.
	Introduction: Polycystic ovary syndrome (PCOS) is among the most prevalent endocrine disorders in women and can lead to many other disorders and chronic diseases. Thus, early diagnosis and treatment of this syndrome is important. Using probiotics, prebiotics, and synbiotics supplementations to treat PCOS seems appropriate because of their useful effects and low complications.; Aims: To assess the effects of probiotics, prebiotics, and synbiotics on hormonal indices such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin, Free Androgen Index (FAI), and inflammatory indices, such as high sensitive C reactive protein (hsCRP), malondialdehyde (MDA), total glutathione (GSH), nitric oxide (NO), and total antioxidant capacity (TAC) as the primary outcomes and the hirsutism score as the secondary outcome.; Methods: All published articles from the beginning until 10 November 2018 in English (Cochrane Library, Web of Sciences, Google Scholar, PubMed, Scopus, and ProQuest) and Persian (SID and Magiran) databases were searched. The effect of interventions on the outcomes was reported with a standard mean difference (SMD) and confidence interval of 95%. In case of high heterogeneity, the random effect model was used instead of the fixed effect model. The statistical heterogeneity of the included clinical trials was tested using the Chi square test and I 2 .; Results: Thirteen studies with 855 participants with PCOS(438 women in the intervention group and 417 women in the control group) were included in the meta-analysis. Results of the meta-analysis showed that the SHBG (SMD: 0.56; 95% CI 0.26-0.86; P = 0.0002) and NO (SMD: 0.38; 95% CI 0.09-0.68; P = 0.01) concentration increased significantly in the probiotics and synbiotics groups compared to the placebo group. FAI (SMD: - 0.58; 95% CI - 0.95 to - 0.21; P = 0.002) and MDA (SMD: - 0.76; 95% CI - 1.46 to - 0.05; P = 0.03) concentration in the probiotics and synbiotics groups reduced significantly compared to the placebo group. The results of meta-analyses on other hormonal and inflammatory indices such as testosterone, DHEAS, GSH, hsCRP, TAC, and hirsutism score showed that there were no significant differences between the intervention and control groups.; Conclusion: Using synbiotics and probiotics in women with polycystic ovary syndrome improve hormonal (FAI, SHBG) and inflammatory (NO, MDA) indices in these patients.

Shamim, H., et al. (2022). "Role of Metformin in the Management of Polycystic Ovarian Syndrome-Associated Acne: A Systematic Review." Cureus 14(8): e28462.
	Metformin, a biguanide hypoglycemic agent that is safe and effective for treating acne in women with the polycystic ovarian syndrome (PCOS), has shown growing evidence of improving insulin resistance, hyperandrogenism, dyslipidemia, overall cardiovascular health, quality of life, psychological wellbeing, and general health outcomes. This study aims to identify and summarize the effects of metformin in patients with PCOS-associated acne. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was done on PubMed, PubMed Central, Cochrane, Google Scholar, and Science Direct databases from 2011 up to 23 February 2022. Randomized controlled trials (RCTs), cross-sectional studies, observational studies, literature reviews, systematic reviews, and meta-analyses published in English were selected. The data was extracted to a predefined template. Each study was individually checked by using a quality assessment. The initial search generated a total of 218 studies. Nine studies were included in the final selection: two RCTs, one hospital-based longitudinal study, one hospital-based clinical trial, three cross-sectional studies, three systematic reviews with meta-analyses, and one narrative review. Metformin is generally effective and safe for improving PCOS-associated acne and the quality of life. More clinical trials are required to determine the indications for prescribing metformin in patients with PCOS-associated acne.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2022, Shamim et al.)

Shamsunisha, Y., et al. (2023). "Aromatherapy for Postpartum Depression: A Systematic Review and Meta-Analysis." Journal of family & reproductive health 17(1): 1-7.
	Objective: The incidence and prevalence of postpartum depression is increasing due to multiple factors. Aromatherapy is a widely used complementary and alternative (CAM) therapy in the management of depression. This systematic review and meta-analysis was done to find the effect of aromatherapy on postpartum depression.; Materials and Methods: Electronic databases like PubMed, Scopus, Cochrane Library and Science Direct since inception till February 2021 were searched using related keywords to obtain eligible studies. Randomised controlled trial studies (RCTs) reporting the effects of aromatherapy therapy in women with postpartum depression were included. Aromatherapy studies conducted on population other than postpartum women were excluded. The primary outcome was depression scores obtained by using valid depression scales. Meta-analysis was performed using the random-effects model of Der Simonian and Laird to produce summary treatment effects in terms of Hedges' g effect sizes with 95% confidence interval (CI).; Results: A total of 4 RCTs (n=303) were included. The results indicate that aromatherapy (Hedges' g =-0.94, 95 CI= -2.55, 0.61, I 2 =88%, p<0.01) reduces depression levels among postpartum women without statistical significance.; Conclusion: The available evidences suggest aromatherapy may be effective in reducing post-partum depression. The number of scientific evidences currently available are very limited and more studies with robust study designs are required to strongly recommend aromatherapy in the management of post-partum depressions. However, being a safer intervention with no adverse effects being reported in previous studies, aromatherapy could definitely be added as an effective complementary therapy in the management of post-partum depression along with conventional medicine.; Competing Interests: Conflict of Interests Authors declare no conflict of interests. (Copyright © 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

shan, h. and q. jie (2022). "Effect of heat-clearing and dampness-eliminating Chinese medicine on cervical high-risk human papillomavirus infection:A systematic review and meta-analysis of radomized controllded trials."
	
Shan, Y., et al. (2022). "Assisted Oocyte Activation With Calcium Ionophore Improves Pregnancy Outcomes and Offspring Safety in Infertile Patients: A Systematic Review and Meta-Analysis." Frontiers in Physiology 12: 751905.
	This study aimed to evaluate the efficacy and safety of calcium ionophore during assisted oocyte activation (AOA). This meta-analysis contained randomized controlled trials and prospective observational and retrospective trials. The summary odds ratio (OR) with 95% confidence intervals (CIs) was calculated for clinical pregnancy rate and live birth rate. Both fixed and random effects models were applied. A total of 22 studies were included into this meta-analysis. Seventeen of the included studies showed that calcium ionophore increased the clinical pregnancy rate (OR, 2.14; 95% CI, 1.38-3.31). Similarly, 14 studies indicated that AOA with calcium ionophore during intracytoplasmic sperm injection (ICSI) improved the live birth rate considerably (OR, 2.65; 95% CI, 1.53-4.60). Moreover, fertilization, blastocyst formation, and implantation rate were higher after using AOA with calcium ionophore combined with ICSI. In addition, calcium ionophore did not increase top-quality embryo rate, cleavage rate, miscarriage rate, congenital birth defects, and neonatal sex ratio. Therefore, calcium ionophore followed by ICSI not only significantly improved live birth and overall pregnancy, but also did not affect the incidence of miscarriage, congenital birth defects, and neonatal sex ratio. This meta-analysis indicated that using calcium ionophore to activate oocytes was beneficial for couples with poor fertilization rates following ICSI.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Shan, Zhao, Zhao, Wang, Cui and Bao.)

Shang, J., et al. (2022). "The effectiveness of postpartum interventions aimed at improving women's mental health after medical complications of pregnancy: a systematic review and meta-analysis." BMC Pregnancy and Childbirth 22(1): 809.
	Background: Postpartum mental disorders including depression and anxiety are common. Medical complications of pregnancy, such as preeclampsia and gestational diabetes, are thought to increase the risk of mental disorders postpartum. However, it is unclear which interventions may be effective for preventing and/or treating postpartum mental disorders following a medically complicated pregnancy. We aimed to systematically review published literature on the effectiveness of postpartum interventions to improve women's mental health after medical complications of pregnancy.; Methods: Systematic review (PROSPERO: CRD42021220030) was performed.; Eligibility Criteria: (1) randomized controlled trials (RCTs), published 1st Jan 2001-12th August 2021 (2) outcome measures reported on postpartum mental disorders (3) participants had ≥ 1 medical complication during pregnancy (4) intervention entirely postpartum or contained a postpartum component (5) full-text available in English or Chinese. Risk of bias was assessed using the Revised Cochrane Criteria Risk of Bias. Random effects inverse-variance weighted meta-analysis was used to pool the individual standardized mean differences (SMD) in depression or anxiety scores between intervention and control groups.; Results: Of 5928 studies screened, 9 met inclusion criteria, and were based on non-pharmaceutical, combined lifestyle interventions that began shortly after childbirth, or as part of extended care packages beginning during pregnancy. Of these, 2 were rated as low risk of bias, 1 with some concerns, and 6 were at high risk. Meta-analysis was performed for 8 studies using standardized measures of depression and 7 for anxiety. There were statistically significant reductions in depression (SMD - 1.48; 95%CI: -2.41 to -0.55), and anxiety scores (SMD - 1.98; 95%CI: -3.03 to -0.94) in intervention versus control groups. Considerable heterogeneity was noted for pooled depression (I 2 = 97.9%, p < 0.05), and anxiety (I 2 = 96.8%, p < 0.05) results.; Conclusion: Limited intervention studies aimed at improving postpartum mental disorders after medically complicated pregnancy were found, most with a high risk of bias. There was some evidence to suggest that postpartum depression and anxiety scores improved after early intervention. However, in general the current quality of evidence is low. Further, high-quality, interventional research is required in this understudied field. (© 2022. The Author(s).)

Shao, F., et al. (2023). "Progestin plus metformin improves outcomes in patients with endometrial hyperplasia and early endometrial cancer more than progestin alone: a meta-analysis." Frontiers in Endocrinology 14: 1139858.
	Objective: Progestin based therapy is the preferred option for fertility-sparing treatment of reproductive-age women with preserved fertility in endometrial hyperplasia (EH) or early endometrial cancer (EEC). Our objective was to investigate whether metformin could enhance the efficacy of progestin-based therapies by meta-analysis.; Methods: We conducted a meta-analysis of randomized or non-randomized controlled trials by searching of PubMed, Embase, Web of science, and Cochrane database from inception to November 8, 2022. The results of enrolled studies were pooled using meta-analysis to estimate the effect of progestin plus metformin on remission, recurrence, pregnancy rate and live birth rate.; Results: In the analysis of progestin administered systemically or locally, complete response (CR) was significantly higher in progestin plus metformin versus progestin alone in the EH group (pooled OR 2.08, 95% CI 1.29 to 3.34, P=0.003), in the EEC group (pooled OR 1.86, 95% CI 1.13 to 3.05, P=0.01), but not in EEC and EH group (pooled OR 1.46, 95% CI 0.97 to 2.21, P=0.07). In the analysis of progestin administered systemically, complete response was improved in progestin plus metformin versus progestin alone, in the EH group (pooled OR 2.47, 95% CI 1.45 to 4.21, P=0.0009), in the EEC group (pooled OR 2.09, 95% CI 1.18 to 3.71, P=0.01), and in the EEC and EH group (pooled OR 2.03, 95% CI 1.16 to 3.54, P=0.01). The relapse rates of patients with EEC and EH were not different (pooled OR 0.54, 95% CI 0.24 to 1.20, P=0.13). For obstetric outcomes, the addition of metformin improved pregnancy rate (pooled OR 1.55, 95% CI 0.99 to 2.42, P=0.05), but not live birth rate (pooled OR 0.95, 95% CI 0.45 to 2.01, P=0.89).; Conclusion: For fertility-sparing management, compared to progestin alone, the outcomes of patients with endometrial hyperplasia and early endometrial cancer were more improved with progestin plus metformin because progestin plus metformin increases the rate of remission and pregnancy.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Shao, Li and Zhao.)

Shao, F., et al. (2020). "Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials." Bioscience reports 40(3).
	Purpose: Poly ADP ribose polymerase (PARP) inhibitors can effectively kill cancer cells by restraining the activity of DNA repair enzymes and utilizing the characteristics of BRCA mutations. This article evaluates the efficacy and safety of PARP inhibitors (PARPis) in the maintenance treatment of ovarian cancer.; Method: We searched for clinical trials in electronic databases. PARPis efficacy were evaluated by the hazard ratios (HR) and its 95% confidence intervals (95% CI) of overall survival (OS) and progression-free survival (PFS) between the PARPis groups and placebo groups, while the PARPis' safety was assessed by relative risk (RR) values of adverse events (AEs) between the two arms.; Results: The immature OS data manifested that patients with BRCA mutation receiving PARPis therapy versus placebo therapy appeared to have longer OS (HR = 0.78, 95%CI = 0.61-1.01; P = 0.06). Compared with placebo group, PARP group had a significant advantage in PFS in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 mutation subgroup (BRCAwt: HR = 0.53, 95%CI = 0.42-0.68, P < 0.00001; BRCAm: HR = 0.30, 95%CI = 0.26-0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI = 0.41-0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29-0.48, P < 0.00001; BRCA2m: HR = 0.23, 95%CI = 0.10-0.57, P = 0.001). Our analysis revealed the incidence rates for AEs of grade ≥3 (grades 3 to 4) and serious AEs in PARPis group were 55.19% and 26.29%, respectively.; Conclusion: Our meta-analysis demonstrates that PARPis therapy can significantly improve PFS in ovarian cancer patients, but it has no benefit in OS. However, the therapy is associated with a significant increase in the risk of AEs of grade ≥ 3 and serious AEs. (© 2020 The Author(s).)

Shao, Y.-H. and T. Tulandi (2019). "Letrozole and Unexplained Infertility: A Contemporary Meta-analysis." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 41(6): 832-834.
	The results of a meta-analysis comparing the efficacy of clomiphene versus letrozole among couples with unexplained infertility in 2014 are in contrast to those of a randomized trial in 2015. This new meta-analysis included randomized studies that were not previously included and found that the efficacy of clomiphene or letrozole in women with unexplained infertility is comparable (Canadian Task Force Classification I). (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Shaogen, G., et al. (2021). "Progestin-primed Ovarian Stimulation Protocol for patients in assisted reproductive technology: a meta-analysis of randomized controlled trials."
	
Shaohua, L. and S. Shorey (2021). "Psychosocial interventions on psychological outcomes of parents with perinatal loss: A systematic review and meta-analysis." International journal of nursing studies 117: 103871.
	Background: Perinatal loss can occur due to miscarriages and ectopic pregnancies, among other circumstances. Psychological health of parents can deteriorate due to perinatal loss. Parent's negative psychological outcomes include depression, anxiety, and grief.; Objective: To evaluate the effectiveness of psychosocial interventions in reducing depression, anxiety, and grief among parents after perinatal loss.; Design: A systematic review and meta-analysis of randomized controlled trials DATA SOURCES: English language articles published from database inception to 19 November 2019 were systematically retrieved from eight electronic databases (CINAHL, Cochrane, EMBASE, ProQuest Dissertations and Theses Global, PsycINFO, PubMed, Scopus, Web of Science).; Review Methods: The Cochrane Risk of Bias tool was used to conduct quality appraisal of each individual article and data was analyzed using Review Manager 5.3. A meta-analysis of randomized controlled trials was conducted using a random-effect model.; Results: Among this review's 17 included studies, 15 studies' results were included in the meta-analyses. The remaining two studies were summarized narratively. Meta-analyses revealed that psychosocial interventions significantly reduced depression (95% CI: -0.64 to -0.29, Z = 5.17, p = <0.00001), anxiety (95% CI: -0.50 to -0.18, Z = 4.21, p < 0.0001) and grief (95% CI: -0.71 to -0.32, Z = 5.12, p < 0.0001).; Conclusion: Psychosocial interventions are effective in improving depression, anxiety, and grief amongst parents with perinatal loss. Psychosocial care can be provided by medical healthcare professionals and expanded with technology-assisted implementation.; Study Registration Number: CRD42019145526.; Competing Interests: Declaration of Competing Interest None. (Copyright © 2021. Published by Elsevier Ltd.)

Shapira-Frommer, R., et al. (2022). "Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study." Gynecologic Oncology 166(2): 211-218.
	Objective: Treatment options for advanced vulvar cancer are limited. We evaluated pembrolizumab monotherapy in patients with advanced vulvar squamous cell carcinoma (SCC) enrolled in the phase 2 multicohort, open-label KEYNOTE-158 study (NCT02628067).; Methods: Eligible patients had histologically or cytologically documented advanced vulvar SCC with prior treatment failure, measurable disease per RECIST v1.1, ECOG performance status 0-1, and a tumor sample available for biomarker analysis. Pembrolizumab 200 mg was administered intravenously Q3W for up to 35 cycles (approximately 2 years). The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent central radiologic review in all patients and subgroups based on PD-L1 combined positive score (≥1 [PD-L1-positive] versus <1 [PD-L1-negative]).; Results: 101 patients were enrolled. Median time from first dose to data cutoff was 36.0 months. The ORR (95% CI) was 10.9% (5.6%-18.7%) among all patients, 9.5% (4.2%-17.9%) among the 84 patients with PD-L1-positive tumors, and 28.6% (3.7%-71.0%) among the 7 patients with PD-L1-negative tumors. Among patients with a response, median DOR was 20.4 (range, 2.1+ to 28.0) months. Median (95% CI) PFS and OS were 2.1 (2.0-2.1) and 6.2 (4.9-9.4) months, respectively. Treatment-related AEs occurred in 50.5% of patients (grade 3-5, 11.9%) and led to discontinuation of treatment in 5.0% of patients. Two deaths were considered treatment-related (hepatitis, n = 2).; Conclusions: Pembrolizumab monotherapy was associated with durable responses in a subset of patients with vulvar SCC. Responses occurred regardless of tumor PD-L1 status. No new safety signals emerged; overall, pembrolizumab was well tolerated.; Competing Interests: Declaration of competing interest Ronnie Shapira-Frommer: study funding to the institution from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD), to support study conduct; honoraria for serving as a speaker from MSD, BMS, AstraZeneca, Novartis, and Roche; personal fees for advisory boards from MSD, Clovis Oncology, and VBL Therapeutics. Linda Mileshkin: study funding to the institution from MSD to support study conduct. Ludmila Manzyuk: study funding to the institution from MSD to support study conduct. Nicolas Penel: study funding to the institution from MSD to support study conduct. Sarina A. Piha-Paul: study funding to the institution from MSD to support study conduct; clinical trial research support from AbbVie, Inc., ABM Therapeutics, Inc., Acepodia, Inc., Alkermes, Aminex Therapeutics, Amphivena Therapeutics, Inc., BioMarin Pharmaceutical, Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Curis, Inc., Cyclacel Pharmaceuticals, Daiichi Sankyo, Eli Lilly, ENB Therapeutics, Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Ltd., Gene Quantum, Genmab A/S, GlaxoSmithKline, Helix BioPharma Corp., HiberCell, Inc., Immunomedics, Inc., Incyte Corp., Jacobio Pharmaceuticals Co., Ltd., Lytix Biopharma AS, MedImmune, LLC, Medivation, Inc., Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Novartis Pharmaceuticals, Pieris Pharmaceuticals, Inc., Pfizer, Principia Biopharma, Inc., Puma Biotechnology, Inc., Rapt Therapeutics, Inc., Seattle Genetics, Silverback Therapeutics, Synlogic, Taiho Oncology, Tesaro, Inc., TransThera Bio, and NCI/NIH (CCSG Shared Resources Grant# P30Ca016672). Matthew Burge: honoraria and study funding to the institution from MSD to support study conduct. Eugenia Girda: study funding to the institution from MSD to support study conduct. Jose A. Lopez Martin: study funding to the institution from MSD to support study conduct; grants, personal fees, and non-financial support from MSD during the conduct of the study; grants, personal fees, and non-financial support from BMS; grants from Merck-Serono; grants and personal fees from Pfizer; personal fees from Bayer|grants and personal fees from Lilly; grants, personal fees, and non-financial support from PharmaMar; grants, personal fees, and non-financial support from Roche; grants and personal fees from Novartis; and personal fees from Pierre-Fabre; current employee of PharmaMar (beginning after this study was conducted). Marloes G.J. van Dongen: study funding to the institution from MSD to support study conduct. Antoine Italiano: study funding to the institution from MSD to support study conduct, grants from MSD, grants from BMS, grants and personal fees from Bayer, personal fees from Springworks, grants from AstraZeneca, grants and personal fees from Roche, grants from Ipsen, grants from PharmaMar. Lei Xu: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. Fan Jin: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. Kevin Norwood: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. Patrick Ott: study funding to the institution from MSD to support study conduct; grants from BMS, Genentech, Celldex, Cytomx, Pfizer, Neon Therapeutics, Armo Biosciences, AstraZeneca, Xencor, and Oncorus; personal fees from Alexion, Amgen, BMS, Genentech, Celldex, Cytomx, Pfizer, Novartis, Neon Therapeutics (now BioNTechUS), and Array. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Shapira-Frommer, R., et al. (2022). "Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) in patients (pts) with cervical cancer naive to PD-1/PD-L1 inhibitors." Cancer Research 82(12 Supplement).
	Background: The anti-TIGIT antibody vibo in combination with pembro was well tolerated across all doses in the dose-escalation phase of the ongoing phase 1 study in pts with advanced solid tumors (NCT02964013); promising antitumor activity of vibo + pembro was observed in anti-PD-1/PD-L1- naive NSCLC. We present initial results of the dose-expansion phase in pts with advanced cervical cancer naive to PD-1/PD-L1 inhibitors. Method(s): Pts with histologically confirmed, locally advanced, or metastatic cervical cancer who failed prior standard-of-care chemotherapy or who experienced early progression on definitive chemoradiation and were naive to PD-1/PD-L1 inhibitors were randomly assigned 1:1 to receive 1 of 2 doses of vibo (200 or 700 mg) + pembro (200 mg) Q3W for <=35 cycles (~2 y) or until PD, toxicity, or pt withdrawal. Primary end points were safety and tolerability. Secondary and exploratory end points included ORR, DOR, and PFS by investigator review per RECIST v1.1. Result(s): Median age of the 80 pts with cervical cancer was 49 y; 58% had an ECOG PS of 1; 53% received >=2 prior lines of therapy; and 61% had PD-L1-positive tumors. 41 pts received vibo 200 mg, and 39 received vibo 700 mg. Median follow-up was 12 mo (range, 5-26). Treatment-related AEs (TRAEs) occurred in 27 pts in each treatment group (66%, vibo 200 mg; 69%, vibo 700 mg). The most frequent TRAEs (>=15%) were rash (22%), increased lipase (17%), and pruritus (17%) with vibo 200 mg + pembro and pruritus (28%), pyrexia (21%), rash (15%), and fatigue (15%) with vibo 700 mg + pembro. Grade 3 or 4 TRAEs occurred in 29% (vibo 200 mg + pembro) and 18% (vibo 700 mg + pembro). No deaths due to TRAEs were reported. Efficacy is reported in the Table. Conclusion(s): Vibo + pembro was safe in pts with advanced cervical cancer. Antitumor activity was comparable between the 2 doses of vibo studied and responses were observed irrespective of PDL1 status. Based on these data, the RP2D for vibo remains 200 mg Q3W.

Shapiro, M., et al. (2023). "Early response with fezolinetant treatment of moderate-to-severe vasomotor symptoms associated with menopause: pooled data from two Phase 3 studies." Maturitas 173: 74.
	Objective: Women suffering from bothersome vasomotor symptoms (VMS) need effective, rapid relief. These analyses assessed early response with fezolinetant using pooled data from SKYLIGHT 1 and 2 (NCT04003155; NCT04003142). In both studies, the four co‐primary efficacy endpoints were met and fezolinetant was safe and well tolerated. Design: SKYLIGHT 1 and 2 were double‐blind, placebo‐controlled Phase 3 studies with the same design. Women aged ≥40–65 years with moderate‐to‐severe VMS (average ≥7 hot flashes/day) were randomized to once‐daily placebo, or fezolinetant 30 mg or 45 mg for 12 weeks. Results: 1022 women were randomized and took ≥1 dose (placebo n=342, fezolinetant 30 mg n=339, fezolinetant 45 mg n=341). A trend in improvement of mean change from baseline in daily moderate and severe VMS frequency vs placebo was seen from day 1. Significant reduction in frequency of moderate and severe VMS was evident from week 1 after start of treatment and was greater in both fezolinetant groups vs placebo. Least squares mean reduction over placebo (SE) at week 1 was –1.59 (0.28), p<0.001 for fezolinetant 30 mg and –1.46 (0.28), p<0.001 for 45 mg. At week 4, these values were –1.89 (0.32), p<0.001 for fezolinetant 30 mg and –2.28 (0.32), p<0.001 for 45 mg. Significant improvement in severity of VMS was also seen as early as week 1 after start of treatment for both fezolinetant doses and was greater with fezolinetant than placebo. Improvements in VMS frequency and severity were sustained throughout the 12‑week double‑blind period. Conclusion: Pooled data from SKYLIGHT 1 and 2 show an effect of fezolinetant on VMS frequency from day 1, reaching statistical significance at weeks 1 and 4. An effect on VMS severity was seen as early as week 1. Both effects were maintained through the 12‐week double‐blind period. Declaration of competing interest Advisory boards/Consulting Fees/Honoraria: Amgen, Aspen, Astellas, BioSyent, Bayer, Duchesnay, GSK, Merck, Mithra, Organon, Pfizer, Searchlight, Sprout, Sunovion, TherapeuticsMD.

Shapiro, M. C. M., et al. (2022). "Effect of fezolinetant treatment on patient-reported sleep disturbance: pooled data from two Phase 3 studies in women with moderate-to-severe vasomotor symptoms associated with menopause." Menopause 29(12): 1484.
	Objective: These analyses assess the effect of fezolinetant on patient-reported sleep disturbance using pooled data from SKYLIGHT 1 and 2 (Phase 3; NCT04003155; NCT04003142). In these studies, fezolinetant significantly improved the frequency and severity of vasomotor symptoms (VMS) vs placebo and was well tolerated. VMS associated with menopause can significantly impact sleep. Design(s): SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies with the same design. Women aged >=40-65 y with moderate-to-severe VMS (average >=7 hot flashes/day) were randomized to oncedaily placebo, or fezolinetant 30 mg or 45 mg for 12 weeks. Sleep was assessed using the Patient-Reported Outcomes Measurement Information System Sleep Disturbance - Short Form (PROMIS SD SF) 8b Total Score, Patient Global Impression of Change - Sleep Disturbance (PGI-C SD), and PGI of Severity - Sleep Disturbance (PGI-S SD). Result(s): The pooled group comprised 1022 women who took >=1 study dose. Fezolinetant 45 mg demonstrated a statistically significant improvement over placebo in sleep disturbance at weeks 4 and 12 using the PROMIS SD SF 8b, PGI-C SD, and PGI-S SD (Table). Fezolinetant 30 mg demonstrated a statistically significant improvement over placebo in sleep disturbance at week 4 using the PROMIS SD SF 8b, at weeks 4 and 12 using the PGI-C SD, and at week 4 using the PGI-S SD (Table). Conclusion(s): Pooled data from SKYLIGHT 1 and 2 further demonstrate the beneficial effect of fezolinetant on three measures of patient-reported sleep disturbance as early as week 4 of treatment.

Shapiro, M. C. M., et al. (2022). "Early response with fezolinetant treatment of moderate-to-severe vasomotor symptoms associated with menopause: pooled data from two randomized Phase 3 studies." Menopause 29(12): 1483-1484.
	Objective: Women suffering from bothersome vasomotor symptoms (VMS) need effective, rapid relief. These analyses assessed early response with fezolinetant using pooled data from SKYLIGHT 1 and 2 (NCT04003155; NCT04003142). In both studies the four co-primary efficacy endpoints were met and fezolinetant was well tolerated. Design(s): SKYLIGHT 1 and 2 were double-blind, placebo-controlled Phase 3 studies with the same design. Women >=40-65 y with moderate-to-severe VMS (average >=7 hot flashes/day) were randomized to once-daily placebo, or fezolinetant 30 mg or 45 mg for 12 weeks. Result(s): 1022 women were randomized and took >=1 dose (placebo n=342, fezolinetant 30 mg n=339, fezolinetant 45 mg n=341). A trend in improvement in mean change from baseline in daily moderate and severe VMS frequency vs placebo was seen from day 1 (Figure). Significant reduction in frequency of moderate and severe VMS was evident from week 1 after start of treatment and was greater in both fezolinetant groups vs placebo. Least squares mean reduction over placebo (SE) at week 1 was -1.59 (0.28), p<0.001 for fezolinetant 30 mg and -1.46 (0.28), p<0.001 for 45 mg. At week 4, these values were -1.89 (0.32), p<0.001 for fezolinetant 30 mg and -2.28 (0.32), p<0.001 for 45 mg. Significant improvement in severity of VMS was also seen as early as week 1 after start of treatment for both fezolinetant doses and was greater with fezolinetant than placebo. Improvements in VMS frequency and severity were sustained throughout the 12-week double-blind period. Conclusion(s): Pooled data from SKYLIGHT 1 and 2 show an effect of fezolinetant on VMS frequency from day 1, reaching statistical significance at weeks 1 and 4. An effect on VMS severity was seen as early as week 1. Both effects were maintained through the 12-week double-blind period.

Sharami, S. R. Y. and E. Saffarieh (2020). "A review on management of gestational trophoblastic neoplasia." Journal of family medicine and primary care 9(3): 1287-1295.
	BACKGROUND: The rare presence of malignant cancerous cells afar any type of pregnancy is known as gestational trophoblastic neoplasia (GTN). GTN are benign lesions which mostly happen due to the activity of extravillous trophoblast cells and the placental villous tree development. These kinds of diseases would be occurring mainly due to the following clinicopathologic conditions: (I) existence of epithelioid trophoblastic tumor (ETT), (II) rare type of choriocarcinoma cancer, (III) gestational trophoblastic tumor of mole, and (IV) the rare malignant tumor of placental site trophoblastic tumor. OBJECTIVE: This comprehensive study is trying to review the most recent approaches in comprehension of pathogenesis, more precise diagnosis, and also the most effective therapeutic procedures for patients who suffer from GTN disorders. MATERIALS AND METHOD: A comprehensive research was carried out on scientific databases of Science Citation Index (SCI), MEDLINE, EMBASE, HMIC, PubMed, CINAHL, Google Scholar, Cochrane Database of Systematic Reviews (CDSR), and PsycINFO over the time period of 2005 to 2019. The keywords which applied for discovering more related records were including: Gestational trophoblastic diseases (GTD), Gestational trophoblastic neoplasia (GTN), molar pregnancy, choriocarcinoma, human chorionic gonadotropin (hCG), diagnosis, management and treatment. CONCLUSION: In spite of the fact that GTN patients are treated with conventional surgical therapies or/and chemotherapy, in some patients with resistant disease, these therapies may not be effective and patients may die. Some novel remedial agents are required for decreasing the level of toxicity caused through administering conventional chemotherapy and also treating the patients who suffer from refractory or resistant disease. The newest issues are related to GTN diagnosis, process of progression of hydatidiform mole (HM) to GTN, and the issue of GTN drug resistance. In this regard, we should have a comprehensive knowledge on GTN genetics for answering all the available questions about this disorder.

Sharara, F. I., et al. (2021). "A narrative review of platelet-rich plasma (PRP) in reproductive medicine." Journal of Assisted Reproduction and Genetics 38(5): 1003-1012.
	Purpose: Platelet-rich plasma (PRP) has become a novel treatment in various aspects of medicine including orthopedics, cardiothoracic surgery, plastic surgery, dermatology, dentistry, and diabetic wound healing. PRP is now starting to become an area of interest in reproductive medicine more specifically focusing on infertility. Poor ovarian reserve, menopause, premature ovarian failure, and thin endometrium have been the main areas of research. The aim of this article is to review the existing literature on the effects of autologous PRP in reproductive medicine providing a summation of the current studies and assessing the need for additional research. Method(s): A literature search is performed using PubMed, MEDLINE, and CINAHL Plus to identify studies focusing on the use of PRP therapy in reproductive medicine. Articles were divided into 3 categories: PRP in thin lining, PRP in poor ovarian reserve, and PRP in recurrent implantation failure. Result(s): In women with thin endometrium, the literature shows an increase in endometrial thickness and increase in chemical and clinical pregnancy rates following autologous PRP therapy. In women with poor ovarian reserve, autologous intraovarian PRP therapy increased anti-Mullerian hormone (AMH) levels and decreased follicle-stimulating hormone (FSH), with a trend toward increasing clinical and live birth rates. This trend was also noted in women with recurrent implantation failure. Conclusion(s): Limited literature shows promise in increasing endometrial thickness, increasing AMH, and decreasing FSH levels, as well as increasing chemical and clinical pregnancy rates. The lack of standardization of PRP preparation along with the lack of large randomized controlled trials needs to be addressed in future studies. Until definitive large RCTs are available, PRP use should be considered experimental.Copyright © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Sharda, R., et al. (2022). "A prospective randomised controlled trial to compare the urinary catheter removal after 24 hours verses 72 hours following vaginal hysterectomy with cystocele repair." Journal of Cardiovascular Disease Research 13(8): 3201-3206.
	Objective: To evaluate the risks and benefits associated with early (24 hours) and late (72 hours) urinary catheter removal following vaginal hysterectomy with cystocele repair. Material(s) and Method(s): Candidates for vaginal repair surgery were 200 women with utero vaginal prolapse with cystocele with or without rectocele stage II to stage IV according to the Pelvic Organ Prolapse Quantifications System, without stress urine incontinence and without recurring urinary tract infections. At the time of the intervention, a urinary catheter (Foley 16) was placed, and it was randomly removed from two groups of patients 24 hours (100 patients) and 72 hours (100 patients) later. Preventive intravenous antibiotics were given for 24 hours to first group and 72 hours for second group. Urine culture was used to detect urinary tract infection (UTI). All the candidates were observed post operatively for any acute urinary retention (AUR) after 8 hours of catheter removal. Calculating percentage frequencies and looking for differences using the chi-square test (x2). Result(s): 4%, and 11%, respectively, of the participants in groups 1 and 2 had UTI. Urinary catheterization time and the presence of UTI were not statistically significantly associated (x2 =3.53, p=0.06). AUR was found among 5% and 1% of the participants respectively in group 1 and 2. AUR was not statistically significantly associated (p=0.18). Recatheterization was 2% and 1% respectively in group 1 and 2, which again is statistically not significantly associated (p=0.56). 2% and 100% respectively, of the participants in groups 1 and 2 had hospital stay for more than 3 days with is statistically significant (p= <0.01) Conclusion(s): Catheter removal after 24 hours of vaginal hysterectomy with cystocele repair reduces the hospital stay, UTI rates and catheter related discomfort of the patient and increases the patient satisfaction level.Copyright © 2022 EManuscript Technologies. All rights reserved.

Shareh, H., et al. (2022). "Emotion-focused group therapy among women with premenstrual dysphoric disorder: A randomized clinical trial." Psychotherapy research : journal of the Society for Psychotherapy Research 32(4): 440-455.
	Objective Premenstrual Dysphoric Disorder (PMDD) contributes to couple burnout, reduced quality of life, sexual dysfunction, and social isolation. The present study aimed to investigate the effectiveness of emotion-focused group therapy (EFGT) in pain perception, self-compassion, sexual function, and couple burnout in women with PMDD. Method: Among married females with PMDD, 72 participants were selected and randomly assigned to experimental and waitlist control groups. EFGT was performed in 10 sessions for the subjects in the experimental groups. The McGill Pain Questionnaire, Self-Compassion Scale, Female Sexual Function Index and Couple Burnout Measure were used to collect data in the pre-test and post-test. To analyze the data, an analysis of covariance test was applied. Results: The findings demonstrated that EFGT was effective in pain perception ( p < .001, η 2 =.80), self-compassion ( p < .001, η 2 = .86), sexual function ( p < .001, η 2 = .38), and couple burnout ( p < .001, η 2 = .70). Participants of EFGT improved well, were satisfied with treatment, and had a good therapeutic relationship. Conclusion: Implementing EFGT increased the components of self-compassion and sexual function, and reduced the components of pain perception and couple burnout. It seems that EFGT could be effective in women with PMDD.

Sharghi, M., et al. (2019). "An update and systematic review on the treatment of primary dysmenorrhea." JBRA Assisted Reproduction 23(1): 51-57.
	Objectives: Primary dysmenorrhea is a painful uterine contraction caused by endometrial laceration. Drug therapies and complementary medicine have been used to treat dysmenorrhea. The aim of this study was to investigate and offer an updated perspective on the treatments for dysmenorrhea.; Methods: The present study was conducted in accordance with the PRISMA checklist for systematic reviews and meta-analyses. The required information was collected based on searches for the following keywords: treatment, primary dysmenorrhea, medicinal plants, chemical drugs, and herbs. Searches were performed on databases Pubmed, Web of Sciences, Scopus, Iran medex, and SID by March 2018 to find literature in the English and Persian languages on this subject without a time limit.; Results: This review included 17 papers, 10 of which on complementary medicine, three on drug therapies, and four on acupuncture and acupressure. The largest and smallest samples had 303 and 24 patients, respectively. Length of treatment ranged from one to six months and the measures most commonly used in the studies were the visual analogue scale and clinical efficacy. Reported complications included gastrointestinal events, nausea, vomiting, diarrhea, abdominal pain, and liver and kidney disorders.; Conclusion: Medicinal plants, drugs, and acupressure seem to suppress pain by reducing the level of prostaglandins, mediating nitric oxide, increasing beta-endorphin levels, blocking the calcium channel, and enhancing circulatory flow through the uterine pathway. Further trials are required to confirm the benefits of the procedures described and ensure the absence of complications.

Sharifi, M., et al. (2024). "The effect of Oenothera biennis (Evening primrose) oil on inflammatory diseases: a systematic review of clinical trials." BMC complementary medicine and therapies 24(1): 89.
	Background: Evening primrose oil (EPO), extracted from the seeds of Oenothera biennis, has gained attention for its therapeutic effects in various inflammatory conditions. Method(s): We performed a systematic search in multiple databases and defined the inclusion criteria based on the following PICOs: P: Patients with a form of inflammatory condition, I: EPO, C: Placebo or other therapeutic interventions, O: changes in inflammatory markers or patients' symptoms; S: randomized controlled trials. The quality of the RCTs was evaluated using Cochrane's RoB tool. Result(s): Several conditions were investigated in the literature. In rheumatoid arthritis, mixed results were observed, with some studies reporting significant improvements in symptoms while others found no significant impact. EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia. However, it did not demonstrate effectiveness in chronic hand dermatitis, tardive dyskinesia, psoriatic arthritis, cystic fibrosis, hepatitis B, premenstrual syndrome, contact lens-associated dry eyes, acne vulgaris, breast cyst, pre-eclampsia, psoriasis, or primary Sjogren's syndrome. Some results were reported from multiple sclerosis after EPO consumption. Studies in healthy volunteers indicated no significant effect of EPO on epidermal atrophy, nevertheless, positive effects on the skin regarding hydration and barrier function were achieved. Conclusion(s): Some evidence regarding the potential benefits of EPO in inflammatory disorders were reported however caution is due to the limitations of the current survey. Overall, contemporary literature is highly heterogeneous and fails to provide strong recommendations regarding the efficacy of EPO on inflammatory disorders. Further high-quality studies are necessitated to draw more definite conclusions and establish O. biennis oil effectiveness as an assuring treatment option in alleviating inflammatory conditions.Copyright © The Author(s) 2024.

Sharifipour, F., et al. (2024). "Effect of Curcumin on Dysmenorrhea and Symptoms of Premenstrual Syndrome: A Systematic Review and Meta-Analysis." Korean journal of family medicine.
	Dysmenorrhea and premenstrual syndrome (PMS) are common periodic and frequent complications in women of reproductive age that can negatively affect health and quality of life. The present study examined the effects of curcumin on the severity of dysmenorrhea and PMS symptoms. A systematic review and meta-analysis of randomized controlled trials was conducted by searching databases such as the Cochrane Library, EMBASE, Scopus, PubMed, and Web of Science from inception to January 2023. Article screening was performed using Endnote ver. X8 (Clarivate). Review Manager (RevMan ver. 5.3; Cochrane) was used for the quality assessment and meta-analysis. A total of 147 studies were screened, of which five were finally selected for quantitative and qualitative analyses. The studies were conducted between 2015 and 2021, and a total of 379 participants with a mean age of 23.33±5.54 years had been recruited in these studies. The meta-analysis showed that curcumin consumption could significantly reduce the severity of dysmenorrhea (mean difference, -1.25; 95% confidence interval [CI], -1.52 to -0.98; three studies; I2=31%) and the overall score of PMS (standardized mean difference, -1.41; 95% CI, -1.81 to -1.02; two studies; I2=0%). The reduction in the severity of PMS and dysmenorrhea has been attributed to curcumin's anti-inflammatory and antidepressant activities. Although the findings suggest that curcumin may be an effective treatment for reducing the severity of PMS and dysmenorrhea, further research with a larger number of participants from various socioeconomic levels and a longer duration of treatment is needed to evaluate the effective dose of curcumin.

Sharifi-Rad, J., et al. (2021). "Cinnamomum Species: Bridging Phytochemistry Knowledge, Pharmacological Properties and Toxicological Safety for Health Benefits." Frontiers in Pharmacology 12: 600139.
	The genus Cinnamomum includes a number of plant species largely used as food, food additives and spices for a long time. Different traditional healing systems have used these plants as herbal remedies to cure diverse ailments. The aim of this comprehensive and updated review is to summarize the biodiversity of the genus Cinnamomum, its bioactive compounds, the mechanisms that underlie the pharmacological activities and molecular targets and toxicological safety. All the data in this review have been collected from databases and recent scientific literature including Web of Science, PubMed, ScienceDirect etc. The results showed that the bioactive compounds of Cinnamomum species possess antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer and neuroprotective effects. The preclinical (in vitro/in vivo) studies provided the possible molecular mechanisms of these action. As a novelty, recent clinical studies and toxicological data described in this paper support and confirm the pharmacological importance of the genus Cinnamomum. In conclusion, the obtained results from preclinical studies and clinical trials, as well as reduced side effects provide insights into future research of new drugs based on extracts and bioactive compounds from Cinnamomum plants.© Copyright © 2021 Sharifi-Rad, Dey, Koirala, Shaheen, El Omari, Salehi, Goloshvili, Cirone Silva, Bouyahya, Vitalini, Varoni, Martorell, Abdolshahi, Docea, Iriti, Calina, Les, Lopez and Caruntu.

Sharma, A., et al. (2021). "Pazopanib based oral metronomic therapy for platinum resistant/refractory epithelial ovarian cancer: A phase II, open label, randomized, controlled trial." Gynecologic Oncology 162(2): 382-388.
	BACKGROUND: Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. PATIENTS AND METHODS: Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. RESULTS: Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has 'not reached' in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in 'symptom scales' in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p < 0.0001, Arm B-p < 0.016). CONCLUSION: Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. TRIAL REGISTRATION: CTRI/2017/10/010219.

Sharma, K. and S. K. Srivastava (2020). "The role of life style modification in management opolycystic ovary syndrome." Indian Journal of Public Health Research and Development 11(11): 106-112.
	Polycystic ovary syndrome is a common endocrine disorder affecting women of reproductive age group characterized by various metabolic and reproductive dysfunctions. There are evidences that environmental toxins play a potential role in disrupting reproductive health. In this review we summarized existing research on a variety of environmental factors involved in the etiology, prevalence and management of polycystic ovary syndrome. Pubmed, PsycINFO and Google Scholar were searched for the reviews and studies from last five years included in this study. All searches were limited to human studies. We concluded that symptoms of polycystic ovary syndrome are reduced with certain dietary supplement, restricted diet and exercise. Health related quality of life along with weight, body hair, infertility, acne score improves well with an intervention of about 24-weeks of lifestyle modification. That is why a healthy lifestyle is usually recommended to improve overall health and fertility.Copyright © 2020, Institute of Medico-Legal Publications. All rights reserved.

Sharma, R., et al. (2023). "RCT to evaluate the necessity of routine luteal phase support after ovarian stimulation by oral ovulogens in intrauterine insemination (IUI) cycles." Human Reproduction 38(Supplement 1): i497-i498.
	Study question: 1. Is it beneficial to provide luteal phase support in each IUI cycle stimulated by oral ovulogens ? Summary answer: 1. Luteal phase support with progesterone makes no significant difference in clinical pregnancy rate in oral ovulogen stimulated IUI cycles. What is known already: ART (assisted reproductive techniques) involves superovulation to achieve the development of multiple follicles. This produces supraphysiological E2 levels that causes feedback inhibition of FSH and LH in luteal phase leading to luteal phase defect. In IUI,only few follicles develop ,so the above phenomenon is rarely seen. Today widespread use of progesterone in clinical practice has become a habit, instead of the need, adding to burden of medication and cost to the patient without much evidence to recommend it. Study design, size, duration: Prospective Randomized control over 1 year 200 IUI cycles randomized to either supplementing luteal phase with tab dydrogesterone (Group A ,no.100) or not supplementing (Group B, No. 100) as per inclusion(Unexplained infertility,Mild male factor,Donor sperm IUI, PCOD,Coital factors,Mild endometriosis) and exclusion criteria(IUI with gonatotropin, age more than 38 years, thin endometrium ,previous two or more IUI failures, history suggestive of luteal phase defect, recurrent pregnancy loss, structural uterine anomaly, history of endocrine or autoimmune diseases) Participants/materials, setting, methods: Transvaginal scan was conducted on day 2 , followed by ovarian stimulation with letrozole 2.5mg for 5 days. HCG trigger (10000IU) was given When follicle reached 18- 24mm with endometrium <7mm and IUI timed 36 hours after. Computer generated random allocation was done with one group receiving luteal phase support with tab dydrogesterone 10mg twice a day(Group A)and other not receiving LPS(Group B).Outcome of study was studied in terms of clinical pregnancy on USG. Main results and the role of chance: Among the patients recruited, infertility was observed to be primary infertility in 74% cases in Group B and 72% in Group A , whereas secondary infertility was observed in 26% cases in group B and 28% in group A (P=0.75). Group B included mild male factor in 29%, 24% of polycystic ovarian syndrome, 17 % tubal, 15% poor ovarian reserve, 9% of unexplained and 6% had endometriosis. Whereas in group A, PCOS (25%),male factor (21%),poor ovarian reserve and unexplained in 20%, endometriosis in 8% and 6% had tubal infertility. Among patients, mean endometrium thickness on trigger day of group Band group A were 8.46 1.36mm and 8.44 +/-1.17mm respectively. Conception was reported by a positive urine pregnancy test . Among Group B , 23% had a positive urine pregnancy test. Whereas, in controls Group A 21% had a positive test, the difference being statistically non-significant (p value = 0.733) Outcomes were expressed terms of clinical pregnancy described as the presence of intrauterine sac with foetal heart rate. Clinical pregnancy rate was 22% of group B and 21% in group A , difference was statistically nonsignificant (p=0.755). Limitations, reasons for caution: Due to limited period of study and hence restricted sample size, the trial needs to be extended over a larger sample size for further interpretation. Further subgroup analysis needs to be conducted when a larger study group is recruited. Wider implications of the findings: This study suggested that luteal support does not significantly affect the clinical pregnancy rate in IUI cycles with oral ovulogens .Our study could be a basis for further analysis to determine whether treatment burden in the form of luteal phase support can be reduced in such patients.

Sharma, V., et al. (2020). "Predictors of response to antidepressants in women with postpartum depression: a systematic review." Archives of Women's Mental Health 23(5): 613-623.
	Antidepressants are the mainstay of drug treatment for moderate or severe postpartum depression. Knowledge of predictors of response could help optimize treatment and reduce the adverse consequences of postpartum depression. The purpose of this systematic review was to ascertain predictors of response or remission to antidepressant treatment in women with postpartum depression. The electronic databases of MEDLINE/PubMed, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, and Evidence-based Medicine Reviews were searched through December 2019. The search was limited to studies published in the English language. Reference lists of articles that met the inclusion criteria were also searched. We identified some predictors of response and remission that could potentially assist in the optimization of drug treatment of postpartum depression; however, caution is needed to apply these findings in clinical practice due to the heterogeneous nature of postpartum depression. The results of our review highlight the urgent need to identify predictors of response, non-response, or remission to antidepressants in women with postpartum depression.

Sharma, V. and A. Sharma (2021). "Olaparib: A narrative drug review." Cancer Research, Statistics, and Treatment 4(2): 335-346.
	Olaparib is an oral anticancer drug that inhibits the poly adenosine diphosphate-ribose polymerase protein (PARP). It is approved for use in advanced ovarian, breast, pancreatic, and prostate cancers. For this review, we comprehensively searched the PubMed database and Google for randomized trials and meta-analyses using the keywords 'breast cancer,' 'pancreatic cancer,' 'ovarian cancer,' 'prostate cancer,' and 'olaparib.' A total of 78 randomized studies, meta-analyses, and other studies were identified, of which 70 were finally included. In this review, we have attempted to elucidate the history, pharmacokinetics, pharmacodynamics, adverse event profile, and special scenarios nvolving the use of olaparib. In addition, we have briefly reviewed the existing literature for its use in ovarian, pancreatic, breast, and prostate cancers.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Sharon, A., et al. (2023). "Nonelectric shaving of endometrial polyp by hysteroscopy - A new technique to eliminate thermal damage." European Journal of Obstetrics, Gynecology, and Reproductive Biology 285: 170-174.
	Objective: To present a new technique for complete endometrial polypectomy, using the bipolar loop hysteroscope, but without the activation of electrical energy, and follow its efficiency and safety for the patient.; Study Design: This is a prospective descriptive study conducted at a university hospital. Forty four patients were recruited to the study according to an intra uterine polyp diagnosed by transvaginal ultrasound (TVS). Out of them 25 really had an endometrial polyp which was inspected by hysteroscopy. Eighteen were at menopause age and seven in their reproductive age. The hysteroscopic removal of the endometrial polyp was performed using the operative loop resectoscope without using electricity, meaning by cold loop. We called this unique technique SHEPH: Shaving of Endometrial Polyp by Hysteroscopy.; Results: The range age was 21-77 years old. All patients with apparently endometrial polyp, underwent a complete removal of the polyp which could be directly seen through hysteroscopy. No bleeding was seen in all cases. The other nineteen patients had normal uterine cavity, so a biopsy was taken according to the indication. The specimen from all cases were sent to histological evaluation. An endometrial polyp was histologically confirmed in all cases who underwent the SHEPH technique, while fragments of an endometrial polyp was revealed by histology in six cases from the group that had normal uterine cavity. No complications were noted for the short and long periods.; Conclusions: Nonelectric Shaving of Endometrial Polyp by Hysteroscopy (SHEPH technique) is a safe and effective procedure which allows the surgeon to achieve a complete endometrial polypectomy but without using electrical energy within the body of the patient. The technique which is easy to learn, is new and unique by eliminate thermal damage in a very common gynecologic indication.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sharp, M. and L. L. C. Dohme (2021). MK-7684A With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors (MK-7684A-005) (KEYVIBE-005).
	No Results Available Biological: Pembrolizumab/Vibostolimab Co-Formulation|Biological: Pembrolizumab|Drug: Lenvatinib|Drug: 5-Fluorouracil|Drug: Cisplatin|Drug: Paclitaxel|Drug: Gemcitabine|Drug: Carboplatin|Drug: Docetaxel|Drug: Bevacizumab|Drug: Capecitabine|Drug: Oxaliplatin Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)|Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR|ORR per RECIST 1.1 as Assessed by Investigator in Participants with Selected Solid Tumors|PFS per RECIST 1.1 as Assessed by Investigator at 9 months|PFS per RECIST 1.1 as Assessed by Investigator at 12 months|Overall Survival (OS)|PFS per RECIST 1.1 as Assessed by Investigator|Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR|DOR per RECIST 1.1 as Assessed by Investigator|ORR per RECIST 1.1 as Assessed by Investigator|PFS per RECIST 1.1 as Assessed by Investigator in Participants with Cervical Cancer|Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30] Items 29 and 30)|Change from Baseline in Physical Functioning Score (EORTC QLQ-C30 Items 1-5)|Number of Participants Who Experienced One or More Adverse Events (AEs)|Number of Participants Who Discontinued Study Intervention Due to an AE All Phase 2 610 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 7684A-005|MK-7684A-005|jRCT2031210335|KEYVIBE-005|2023-505284-36|2021-001009-56 February 22, 2027

Sharp, M. and L. L. C. Dohme (2021). Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016).
	No Results Available Drug: Pembrolizumab|Drug: Belzutifan|Drug: Lenvatinib Arm 1: Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)|Arm 1: Number of Participants Who Experience at Least One Adverse Event (AE)|Arm 1: Number of Participants Who Discontinue Study Treatment Due to an AE|Confirmed Objective Response Rate (ORR) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)|Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR|Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR|Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR|Overall Survival (OS)|ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR|DOR Per mRECIST 1.1 for HCC as Assessed by BICR|DCR Per mRECIST 1.1 for HCC as Assessed by BICR|PFS Per mRECIST 1.1 for HCC as Assessed by BICR|Arm 2: Number of Participants Who Experienced an Adverse Event (AE)|Arm 2: Number of Participants Who Discontinued Study Treatment Due to an AE All Phase 2 730 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 6482-016|MK-6482-016|2020-005007-40 August 18, 2026

Sharp, M. and L. L. C. Dohme (2021). Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65).
	No Results Available Biological: Pembrolizumab|Drug: Paclitaxel|Drug: Bevacizumab|Other: Placebo for pembrolizumab|Drug: Docetaxel Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator|Overall Survival (OS)|PFS per RECIST 1.1 by Blinded Independent Central Review (BICR)|Number of Participants who Experience an Adverse Event (AE)|Number of Participants who Discontinue Study Treatment due to an AE|Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)|Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30|Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale|TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale Female Phase 3 616 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 3475-B96|MK-3475-B96|KEYNOTE-B96|ENGOT-ov65|jRCT2051210184|2023-506177-35|2020-005027-37 August 31, 2027

Sharp, M., et al. (2023). MK-2870 in Post Platinum and Post Immunotherapy Endometrial Cancer (MK-2870-005).
	No Results Available Biological: MK-2870|Drug: Doxorubicin|Drug: Paclitaxel Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)|Overall Survival (OS)|Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR|Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR|Number of Participants Who Experience One or More Adverse Events (AEs)|Number of Participants Who Discontinue Study Intervention Due to an AE|Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30]) Female Phase 3 710 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2870-005|2023-504816-14|U1111-1288-7581 January 10, 2028

Sharp, M., et al. (2022). Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15).
	No Results Available Biological: pembrolizumab|Drug: carboplatin|Drug: paclitaxel|Drug: docetaxel|Drug: cisplatin Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)|Overall Survival|Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)|Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)|Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)|Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator|Progression-Free Survival 2 (PFS2) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator|Number of Participants Who Experience at Least One Adverse Event (AE)|Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)|Change From Baseline in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) (Item 29) And Quality of Life (QoL) (Item 30) Combined Score|Change From Baseline in European Organization for Research And Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Combined Score Female Phase 3 280 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 3475-C93|MK-3475-C93|KEYNOTE-C93|GOG-3064|ENGOT-en15|jRCT2011210065|2021-003185-12 July 17, 2026

Shattuck, L. and Inc (2022). Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers.
	No Results Available Drug: Pegylated Liposomal Doxorubicin + SL-172154|Drug: Mirvetuximab + SL-172154 Evaluate safety and tolerability of SL-172154 when administered with PLD|Evaluate safety and tolerability of SL-172154 when administered with MIRV|Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered with PLD|Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered with MIRV|To assess preliminary evidence of anti-tumor activity of SL-172154 when administered with PLD|To assess preliminary evidence of anti-tumor activity of SL-172154 when administered with MIRV|Immunogenicity to SL-172154|Immunogenicity to MIRV|Maximum serum concentration (Cmax) of SL-172154|Maximum serum concentration (Cmax) of MIRV|Maximum serum concentration (Cmax) of Total Antibody|Maximum serum concentration (Cmax) of DM4 Payload|Maximum serum concentration (Cmax) of S-Methyl DM4 Payload|Area under the serum concentration-time curve (AUC) of SL-172154|Area under the serum concentration-time curve (AUC) of MIRV|Area under the serum concentration-time curve (AUC) of Total Antibody|Area under the serum concentration-time curve (AUC) of DM4 Payload|Area under the serum concentration-time curve (AUC) of S-Methyl DM4 Payload|Terminal elimination half-life (t1/2) of SL-172154|Terminal elimination half-life (t1/2) of MIRV|Terminal elimination half-life (t1/2) of Total Antibody|Terminal elimination half-life (t1/2) of DM4 Payload|Terminal elimination half-life (t1/2) of S-Methyl DM4 Payload Female Phase 1 102 Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment SL03-OHD-105 April 2025

Shayne, F., et al. (2023). "The Effect of Long-Term Dienogest Use on Bone Mineral Density: A Systematic Review and Meta-Analysis."
	
Shea, M., et al. (2024). Dostarlimab and Cobolimab in Advanced Cervical Cancer.
	No Results Available Drug: Dostarlimab|Drug: Cobolimab Objective Response Rate (ORR) Based on irRECIST|Median Progression-Free Survival (PFS)|Median Overall Survival (OS)|Immune-Related (PFS) Progression-Free Survival|Grade 3-5 Adverse Events Rate Female Phase 2 66 Other|Industry Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 23-560 July 15, 2027

Sheikh, S., et al. (2023). "Lipid-based amphotericin B gel treatment eradicates vulvovaginal candidiasis in patients who failed to azole therapy." Archives of dermatological research 315(7): 1939-1944.
	Vaginal yeast infection is one of the most common diseases caused by vulvovaginal candidiasis (VVC). Effective therapy for VVC is needed. A lipid-based amphotericin B gel 0.1% (LAB) was developed and evaluated for the treatment of VVC patients and those who failed to azole therapy. LAB was applied topically twice daily for 7 days to 64 moderate patients and 14 days to 55 severely infected VVC patients. Additionally, 66 patients who failed to azole therapy were treated twice daily with LAB for 14 days. A 91.5% clinical response and 93.16% mycological response was observed in VVC patients. The patients treated with LAB who failed to azole therapy showed a 75% clinical, 95.3% mycological response and 83% remission was observed.Overall, the LAB was found to be efficacious and safe for the treatment of VVC patients. Clinical Trial Registration All the trials were registered at Clinical Trial Registry of India (CTRI/2013/02/003378, CTRI/2014/02/004409). (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Shele, G., et al. (2020). "A Systematic Review of the Effects of Exercise on Hormones in Women with Polycystic Ovary Syndrome." Journal of functional morphology and kinesiology 5(2).
	Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by menstrual irregularity and elevated serum androgens, and is often accompanied by insulin resistance. The etiology of PCOS is unknown. Lifestyle interventions and weight loss, where appropriate, remain first-line treatments for women with PCOS. Regular physical activity is recommended for women with PCOS to maintain a healthy weight and cardiovascular fitness.; Purpose: To review the evidence for the impact of various exercise interventions on hormone levels in women with PCOS.; Methods: A systematic review of original studies indexed in PubMed that utilized an exercise intervention in women with PCOS and reported hormone values pre- and post-intervention. Studies in which the effects of the exercise intervention could be determined were included.; Results: Vigorous aerobic exercise improves insulin measures in women with PCOS. Resistance or strength training may improve androgen levels, though additional studies are warranted. Studies with yoga are limited but suggest improvements in androgens. Limited information is available on the impact of exercise on adipokines and anti-Müllerian hormone, warranting further investigation.; Conclusions: Recommended guidelines for women with PCOS include vigorous aerobic exercise and resistance training to improve measures of insulin sensitivity and androgen levels.

Shen, H., et al. (2023). "Effects of epidural anesthesia on the prognosis of ovarian cancer-a systematic review and meta-analysis." BMC anesthesiology 23(1): 390.
	Introduction: The global low survival rate among ovarian cancer patients has resulted in significant social and economic burdens. Nevertheless, previous studies have produced mixed results when exploring the link between anesthetic techniques and the prognosis of ovarian cancer. The study aims to compare the effect of epidural anesthesia with general anesthesia on survival time after cytoreductive surgery in patients with ovarian cancer.; Methods: The PubMed (National Library of Medicine), Cochrane library, Web of science, Embase, CNKI (China National Knowledge Internet), Wanfang Med Online (China database), were systematically searched from inception to May, 2023, using the Medical Subject Headings [MeSH] of "Ovarian Neoplasm" and "Anesthesia, Epidural" and free words to identify systematic reviews or meta-analyses. The research methodology involved analyzing randomized controlled trials (RCTs), as well as prospective or retrospective cohort studies, which compared the long-term prognosis of patients with ovarian cancer under general anesthesia combined with epidural anesthesia (GEA) versus general anesthesia alone (GA). The Newcastle Ottawa Scale (NOS) was used to assess methodological quality and bias. Data extraction and assessment of study quality were conducted by two independent reviewers. A meta-analysis was then performed to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Overall survival (OS) was defined as the primary outcome, time to tumor recurrence (TTR) was the secondary outcome. Epidural anesthesia could be used intraoperatively and immediately postoperatively (EIP), or postoperatively only (EP). GEA includes EIP and EP.; Results: In total, 8 retrospective cohort studies with 2036 participants met the inclusion criteria. The pooled results demonstrated that GEA could extend OS (HR 0.75, 95% CI 0.67-0.84, I 2 = 0%, P < 0.05, fixed-effect model) when compared with GA in ovarian cancer patients undergoing cytoreductive surgery, but not TTR (sensitivity analysis revealed substantial heterogeneity among the included studies). The result of analyzing a total of 1490 patients in 4 studies was that EIP had a better prognosis on OS than GA (HR 0.68, 95%CI 0.55-0.85, I 2 = 61%, P < 0.05, random-effect model). However, EP had no advantage in TTR (sensitivity analysis revealed it was unstable outcome). Ovarian cancer FIGO(International Federation of Gynecology and Obstetrics) stage III, stage IV compared to stage I on OS was statistically significant, HRs respectively are 3.67 (95%CI 2.25-5.98), I 2 = 0%, fixed-effect model, P < 0.05, and 7.43 (95%CI 3.67-15.03), I 2 = 31%, fixed-effect model, P < 0.05, but there was no statistically significant difference between stage II and stage I, HR 2.00, 95%CI0.98-4.09, I 2 = 0%, fixed-effect model, P > 0.05. 1-10 mm tumor residuals shorten TTR compared with 0 residuals, HR 1.75, 95% CI1.50-2.04, I 2 = 0%, fixed-effect model, P < 0.05.; Conclusions: It is hard to conclude that postoperative epidural analgesia offers greater benefits than GA. However, general anesthesia combined with epidural anesthesia (EIP) can improve overall survival in ovarian cancer patients, allowing the anesthesiologist to use anesthesia techniques to provide a favorable prognosis for the ovarian cancer patient. Tumor staging and the extent of cell reduction are also critical factors that significantly influence the long-prognosis of ovarian cancer patients. (© 2023. The Author(s).)

Shen, L., et al. (2021). "Astragalus-Containing Chinese Herbal Medicine Combined With Chemotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis." Frontiers in Pharmacology 12: 587021.
	Background: Cervical cancer is the fourth most common malignant tumor among women worldwide. This study aimed to evaluate the efficacy of Astragalus-containing Chinese herbal medicine (CHM) combined with chemotherapy (CT) for the treatment of cervical cancer. Methods: Ten electronic databases including PubMed, Cochrane Library, Embase, Korean databases, and Chinese medical databases, were systematically searched up to July 2020. All randomized controlled trials using Astragalus-containing CHM combined with CT to treat cervical cancer were included. Results: A total of 19 trials were included in the analysis. Compared with the control group, the Astragalus-containing CHM combined with CT group showed a significantly increased tumor response (complete and partial response (CR and PR)) (risk ratio [RR] = 1.25, 95% confidence interval [CI]: 1.17-1.33, p < 0.00001) and Karnofsky performance score (KPS) (standardized mean difference [SMD] = 1.81, 95% CI: 1.46-2.17, p < 0.00001). This group also displayed remarkably reduced CT toxicity. Conclusion: Our study suggests that Astragalus-containing CHM might be a potential option for cervical cancer to enhance the curative efficacy and reduce CT toxicity.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Shen, Gwak, Cui, Joo and Park.)

Shen, L. P., et al. (2022). "Strumal Carcinoid Tumor of the Ovary: Report of Rare Occurrence with Review of Literature." Diagnostics 12(11): 2706.
	The primary ovarian carcinoid tumor is a very rare ovarian tumor, which accounts for approximately 0.5% to 1.7% of all carcinoids and 1% of ovarian cancer. According to its histopathological features, it can be divided into four categories: insular, trabecular, strumal, and mucinous, among which insular carcinoid is common in Western countries. By comparison, the chain-typed and trabecular carcinoid seem to be common in Asian countries. To date, about 150 cases have been reported in the world, and 40% of them are strumal carcinoid tumor of the ovary (SCTO), which is a highly specialized teratoma differentiated from the monomer, and often characterized by the coexistence of thyroid follicular tissue and carcinoid tissue with the neuroendocrine function. Preoperative diagnosis may be difficult due to the very insidious nature of the disease and its multiple imaging manifestations. We reported the case of a 39-year-old woman with a 5-year clinical history. Gynecologic examination and ultrasonic testing revealed an enlarged ovary with a diameter of about 60 mm, accompanied by a hypoechoic area, which was suspected to be a benign teratoma. Ca-125, AFP, free T4, TSH, and other diagnostic indicators were normal. During the laparoscopic oophorocystectomy of the left ovary, a smooth and solid tumor with the size of 6 x 6 x 5 cm was found in the right ovary. During the operation, a mature cystic teratoma containing a struma was frozen, then the oophorocystectomy of the left ovary was performed. According to the Federation International of Gynecology and Obstetrics (FIGO) in 2014, histopathological examination showed a mature teratoma with thyroid carcinoid stage Ic, and Douglas's cystic hygroma cytopathology was negative. One year after the operation, the patient was tumor-free, with Ca-125, FT4, and TSH being within the normal range. Specific diagnostic tools and serological monitoring of malignant tumors of the ovary have low specificity and sensitivity in the diagnosis of this rare malignant tumor of the ovary. Female patients with habitual constipation, chronic abdominal colic, diarrhea, and endocrine dysfunction also need to be alert to this rare malignant tumor of the ovary.Copyright © 2022 by the authors.

Shen, L.-Y., et al. (2023). "Comparison of the efficacy of different frequency electroacupuncture in the treatment of polycystic ovary syndrome patients with abdominal obesity." Zhen ci yan jiu = Acupuncture research 48(12): 1266-1273.
	Objectives: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity.; Methods: PCOS patients with abdominal obesity were randomly divided into low-frequency group ( n =29) and dilatational wave group ( n =29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated.; Results: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency ( P <0.01, P <0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score ( P <0.01, P <0.05)；the dilatational wave group showed decreased serum AMH contents ( P <0.05) and increased serum SHBG contents ( P <0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased ( P <0.01, P <0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction ( P <0.05) in WC after treatment.; Conclusions: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.

Shen, W., et al. (2021). "The Effects of Salvia miltiorrhiza on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2021: 9971403.
	Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. As a traditional medicine, Salvia miltiorrhiza ( S. miltiorrhiza) has been widely used in the treatment of many gynecological diseases, but the efficacy of S. miltiorrhiza in women with PCOS has not been assessed. The purpose of this systematic review and meta-analysis was to evaluate the effectiveness and safety of S. miltiorrhiza in women with PCOS.; Methods: We conducted searches in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical database from inception to December 23, 2020, to identify studies that met the inclusion criteria. The quality of the evidence was estimated using the Cochrane Reviewer Handbook 5.0.0, and the meta-analysis was performed using RevMan 5.3.5 software.; Results: Six randomized controlled trials (RCTs) involving 390 patients with PCOS were included. The studies suggested that S. miltiorrhiza extract combined with letrozole (LET) was more effective in improving pregnancy rate (RR: 2.60, 95% CI: 1.06 to 6.39, P =0.04) compared to LET alone. S. miltiorrhiza extract was associated with decreased fasting blood glucose (MD: -0.25, 95% CI: -0.37 to -0.13, P < 0.0001), fasting insulin (MD: -1.16, 95% CI: -1.74 to -0.58, P < 0.0001), total cholesterol (TC) (MD: -0.58, 95% CI: -0.72 to -0.43, P < 0.00001), and triglycerides (TG) (MD: -0.31, 95% CI: -0.35 to -0.26, P < 0.00001) compared with placebo, but not with improvements in body mass index or waist-to-hip ratio (MD: -1.41, 95% CI: -4.81 to 2.00, P =0.42; MD: -0.02, 95% CI: -0.05 to 0.01, P =0.16, respectively). There was a significant difference between S. miltiorrhiza extract combined with cyproterone acetate (CPA) and CPA alone in terms of decreasing TC (MD: -0.77, 95% CI: -0.89 to -0.65, P < 0.00001), TG (MD: -0.43, 95% CI: -0.65 to -0.20, P < 0.0001), and low-density lipoprotein cholesterol (MD: -0.49, 95% CI: -0.66 to -0.33, P < 0.00001) and increasing high-density lipoprotein cholesterol (MD: 0.30, 95% CI: 0.20, 0.40, P < 0.00001). In addition, S. miltiorrhiza extract also decreased testosterone, follicle-stimulating hormone, and luteinizing hormone. The studies did not mention any adverse events with S. miltiorrhiza extract.; Conclusion: The current studies indicate that S. miltiorrhiza has beneficial effects on reproduction and glucose and lipid metabolism in patients with PCOS, and it is generally safe for clinical application. However, more prospective RCTs with large samples, multiple centers, and longer intervention duration are needed in the future to obtain more reliable conclusions.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2021 Wenjuan Shen et al.)

Shenker, R., et al. (2023). "Adaptive Positron Emission Tomography Radiation Therapy in Patients With Locally Advanced Vulvar Cancer: A Prospective Study." Advances in Radiation Oncology 8(4): 101208.
	Purpose: In this prospective trial, we aim to determine whether fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT)-based adaptive radiation therapy (ART) improves dosimetry outcomes for patients treated with definitive radiation for locally advanced vulvar cancer.; Methods and Materials: Patients were enrolled in 2 sequential institutional review board-approved prospective protocols for PET/CT ART from 2012 to 2020. Patients were planned with pretreatment PET/CT to 45 to 56 Gy in 1.8 Gy/fraction, followed by a boost to gross disease (nodal and/or primary) to a total of 64 to 66 Gy. Intratreatment PET/CT was obtained at 30 to 36 Gy, and all patients were replanned to the same dose goals with revised organ at risk (OAR), gross tumor volume, and planned target volume contours. Radiation therapy consisted of either intensity modulated radiation therapy or volumetric modulated arc therapy. Toxicity was graded by Common Terminology Criteria for Adverse Events, version 5.0. Local control, disease-free survival, overall survival, and time to toxicity were estimated using the Kaplan-Meier method. Dosimetry metrics for OARs were compared using the Wilcoxon signed rank test.; Results: Twenty patients were eligible for analysis. Median follow-up among surviving patients was 5.5 years. Local control, disease-free survival, and overall survival at 2 years were 63%, 43%, and 68%, respectively. ART significantly reduced the following OAR doses: bladder, maximum dose (D max ; median reduction [MR], 1.1 Gy; interquartile range [IQR], 0.48-2.3 Gy; P < .001) and D 2cc (MR, 1.5 Gy; IQR, 0.51-2.1 Gy; P < .001); bowel, D max (MR, 1.0 Gy; IQR, 0.11-2.9 Gy; P < .001), D 2cc (MR, 0.39 Gy; IQR, 0.023-1.7 Gy; P < .001), and D 15cc (MR, 0.19 Gy; IQR, 0.026-0.47 Gy; P = .002); and rectal, mean dose (MR, 0.66 Gy; IQR, 0.17-1.7 Gy; P = .006) and D 2cc (MR, 0.46 Gy; IQR, 0.17-0.80 Gy; P = .006). No patients experienced any grade ≥3 acute toxicities. There were no reported late grade ≥2 vaginal toxicities. Lymphedema at 2 years was 17% (95% confidence interval, 0%-34%).; Conclusions: Doses to bladder, bowel, and rectum were significantly improved with ART, though the median magnitudes were modest. Which patients benefit most from adaptive treatment is a matter for future investigation. (© 2023 The Author(s).)

Shepherd, E. and M. Grivell Rosalie (2020). "Aspirin (single dose) for perineal pain in the early postpartum period." The Cochrane Database of Systematic Reviews 7: CD012129.
	Background: Perineal trauma, due to spontaneous tears, surgical incision (episiotomy), or in association with operative vaginal birth, is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain, and its effectiveness and safety should be assessed. This is an update of the review, last published in 2017.; Objectives: To determine the effects of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain.; Search Methods: For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register (4 October 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (4 October 2019) and screened reference lists of retrieved studies.; Selection Criteria: Randomised controlled trials (RCTs), assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol or acetaminophen, for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs, but none were identified. We excluded quasi-RCTs and cross-over studies.; Data Collection and Analysis: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The certainty of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach.; Main Results: We included 17 RCTs, 16 of which randomised 1132 women to aspirin or placebo; one RCT did not report numbers of women. Two RCTs (of 16) did not contribute data to meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear, due to poor reporting. We included four comparisons: aspirin versus placebo (15 RCTs); 300 mg versus 600 mg aspirin (1 RCT); 600 mg versus 1200 mg aspirin (2 RCTs); and 300 mg versus 1200 mg aspirin (1 RCT). Aspirin versus placebo Aspirin may result in more women reporting adequate pain relief four to eight hours after administration compared with placebo (risk ratio (RR) 2.03, 95% confidence interval (CI) 1.69 to 2.42; 13 RCTs, 1001 women; low-certainty evidence). It is uncertain whether aspirin compared with placebo has an effect on the need for additional pain relief (RR 0.25, 95% CI 0.17 to 0.37; 10 RCTs, 744 women; very low-certainty evidence), or maternal adverse effects (RR 1.08, 95% CI 0.57 to 2.06; 14 RCTs, 1067 women; very low-certainty evidence), four to eight hours after administration. Analyses based on dose did not reveal any clear subgroup differences. 300 mg versus 600 mg aspirin It is uncertain whether over four hours after administration, 300 mg compared with 600 mg aspirin has an effect on adequate pain relief (RR 0.82, 95% CI 0.36 to 1.86; 1 RCT, 81 women) or the need for additional pain relief (RR 0.68, 95% CI 0.12 to 3.88; 1 RCT, 81 women). There were no maternal adverse effects in either aspirin group. 600 mg versus 1200 mg aspirin It is uncertain whether over four to eight hours after administration, 600 mg compared with 1200 mg aspirin has an effect on adequate pain relief (RR 0.85, 95% CI 0.52 to 1.39; 2 RCTs, 121 women), the need for additional pain relief (RR 1.32, 95% CI 0.30 to 5.68; 2 RCTs, 121 women), or maternal adverse effects (RR 3.00, 95% CI 0.13 to 69.52; 2 RCTs, 121 women). 300 mg versus 1200 mg aspirin It is uncertain whether over four hours after administration, 300 mg compared with 1200 mg aspirin has an effect on adequate pain relief (RR 0.62, 95% CI 0.29 to 1.32; 1 RCT, 80 women) or need for additional pain relief (RR 2.00, 95% CI 0.19 to 21.18; 1 RCT, 80 women). There were no maternal adverse effects in either aspirin group. None of the included RCTs reported on neonatal adverse effects. No RCTs reported on secondary review outcomes of: prolonged hospitalisation due to perineal pain; re-hospitalisation due to perineal pain; fully breastfeeding at discharge; mixed feeding at discharge; fully breastfeeding at six weeks; mixed feeding at six weeks; perineal pain at six weeks; maternal views; or maternal postpartum depression.; Authors' Conclusions: Single dose aspirin may increase adequate pain relief in women with perineal pain post-episiotomy compared with placebo. It is uncertain whether aspirin has an effect on the need for additional analgesia, or on maternal adverse effects, compared with placebo. We downgraded the certainty of the evidence because of study limitations (risk of bias), imprecision, and publication bias. Aspirin may be considered for use in non-breastfeeding women with post-episiotomy perineal pain. Included RCTs excluded breastfeeding women, so there was no evidence to assess the effects of aspirin on neonatal adverse effects or breastfeeding. Future RCTs should be designed to ensure low risk of bias, and address gaps in the evidence, such as the secondary outcomes established for this review. Current research has focused on women with post-episiotomy pain; future RCTs could be extended to include women with perineal pain associated with spontaneous tears or operative birth. (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Sheridan, W., et al. (2021). "Weight loss with bariatric surgery or behaviour modification and the impact on female obesity-related urine incontinence: A comprehensive systematic review and meta-analysis." Clinical Obesity 11(4): e12450.
	Women with obesity are at risk of pelvic floor dysfunction with a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index >=30 kg/m2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta-analysis will assess this recommendation to aid in the counselling of women with obesity-related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty-three studies and their outcomes were meta-analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI-20, SMD -0.774 (95% CI [-1.236, -0.312]). This systematic review and meta-analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity-related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity-related UI are needed to confirm this study's findings.Copyright © 2021 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Sherman Kerry, A., et al. (2023). "A supportive text message intervention for individuals living with endometriosis (EndoSMS): Randomized controlled pilot and feasibility trial." Contemporary clinical trials communications 32: 101093.
	Introduction: As a high symptom burden chronic condition, endometriosis is associated with diminished quality of life (QoL) and psychological distress. The EndoSMS text message intervention was developed to inform and support individuals living with endometriosis. The primary aim of this study is to assess the acceptability, feasibility and preliminary efficacy of EndoSMS, to improve endometriosis-specific QoL and reduce psychological distress in a randomised controlled trial, compared with care as usual. We will additionally assess the impact of EndoSMS on self-efficacy for managing endometriosis.; Methodology: A two-arm parallel pilot randomised controlled trial with waitlist control was conducted. Baseline assessments included QoL, psychological distress, self-efficacy, demographic and medical variables. Following baseline survey completion, participants were randomised to either the Intervention (EndoSMS: 3-months of text messaging) or Control condition. At 3-month follow-up, all participants completed an online survey reassessing outcomes, and Intervention participants provided quantitative and qualitative user feedback on EndoSMS.; Results: Data collection commenced on 18 November 2021 and was completed on 30 March 2022. Descriptive statistics will be used to analyse feasibility and acceptability of the intervention. Preliminary efficacy analyses will be conducted using linear mixed models for QoL, psychological distress and self-efficacy outcomes. Subgroup analyses will also be conducted for typically underserved populations (e.g., rural/regional).; Conclusion: This pilot will provide acceptability, feasibility and preliminary efficacy evidence for the impact of a supportive text messaging program for endometriosis. It will contribute to understanding how to optimally support individuals in living with and managing their endometriosis.; Trial Registration: Australian New Zealand Clinical Trials Registry.; Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Funding for this project was granted by Endometriosis Australia. JR is funded by a NHMRC Investigator Grant Leadership Level 2 [GNT2007946]. AS receives a PhD stipend provided by the University of Sydney, Australian Government Research Training Program Scholarship and a Supplementary Postgraduate Research Scholarship in Breast Cancer. (© 2023 Published by Elsevier Inc.)

Sheshpari, S., et al. (2019). "Ovarian function and reproductive outcome after ovarian tissue transplantation: a systematic review." Journal of translational medicine 17(1): 396.
	The aim of this systematic review study is to summarize the current knowledge of ovarian tissue transplantation and provide insight on ovarian function, fertility and reproductive outcome following ovarian tissue transplantation. Relevant studies were identified by searching through PubMed, Cochrane Library, Embase, ProQuest, and Scopus databases until August 2018. Ovarian function by examination of the hormonal level was evaluated, together with follicular growth, the return of menstrual cycle and assessment of reproductive consequences: pregnancy, miscarriage rates and live birth after transplantation. Studies including female patients aged between 22 and 49 years that were subjected to ovarian tissue transplantation were considered. A total of 1185 studies were identified in the primary search. Titles and abstracts were screened for assessment of the inclusion criteria. Finally, twenty-five articles met the criteria and were included in this study. In general, 70% of patients that underwent ovarian tissue transplantation had ovarian and endocrine function restoration as well as follicular growth. Pregnancy was reported with 52% of the patients. The available evidence suggests that ovarian tissue transplantation is a useful and an applied approach to restore hormonal function, endocrine balance and eventually fertility outcomes in patients that are predisposed to lose their fertility, diagnosed with premature ovarian failure (POF), as well as women undergoing cancer treatments. Identification of the techniques with the lowest invasions for follicular and oocyte development after ovarian tissue transplantation aiming to reduce probable adverse effects after treatment is indispensable.

Shi, C., et al. (2019). "Comparison of efficacy of robotic surgery, laparoscopy, and laparotomy in the treatment of ovarian cancer: a meta-analysis." World Journal of Surgical Oncology 17(1): 162.
	Background: We intended to compare the clinical effect of robotic surgery with laparoscopy and laparotomy in ovarian cancer treatment.; Methods: The included studies were retrieved from PubMed, Embase, and the Cochrane Library databases. The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the study quality. Effect measures were presented with weighted mean difference (WMD)/odds ratio (OR) and 95% confidence interval (CI), and heterogeneity test was assessed using Q test and I 2 statistics to determine the use of the random effects model or fixed effects model. Egger's test was used to assess the publication bias.; Results: A total of eight studies was included in this meta-analysis with a MINORS score of 16-18. In the random effects model, estimated blood loss (EBL) of robotic surgery was significantly less compared with laparotomy (WMD = - 521.7027, 95% CI - 809.7816; - 233.6238). In the fixed effects model, length of hospital stay (LHS) (WMD = - 5.2225, 95% CI - 6.1485; - 4.2965) and postoperative complication (PC) (OR = 0.4710, 95% CI 0.2537; 0.8747) of robotic surgery were significantly less, and overall survival (OS) rate (OR = 6.4355, 95% CI 1.6722; 24.7678, P = 0.0070) of robotic surgery was significantly higher compared with laparotomy. There was no difference in the effect size of all variables between robotic surgery and laparoscopy. Meanwhile, a publication bias (t = 6.8290, P = 0.002405) was only identified for PC in robotic surgery and laparotomy groups; no publication bias was identified for the other variables.; Conclusions: Despite the above results, it failed to show oncological safety and recurrence by pathological stages or histologic types in this meta-analysis, and those confounding factors might affect the clinical outcome. Future meta-analyses with a larger number of eligible randomized controlled trial studies were needed to determine the most suitable treatment method for patients with different stages and types of ovarian cancer.

Shi, S., et al. (2021). "The efficacy and safety of Xuefu Zhuyu Decoction combined Mifepristone in the treatment of Uterine leiomyoma: A protocol systematic review and meta-analysis." Medicine 100(3): e24306.
	Background: Uterine leiomyoma (UL) is a common severe gynecological issue. In China, Xuefu Zhuyu Decoction (XFZYD), combined with Mifepristone, is widely used in the treatment of UL. However, their combined effectiveness and safety for this purpose have not yet been explored.; Objective: This systematic review aims to evaluate the effectiveness and safety of XFZYD combined with Mifepristone as a method of treatment for UL.; Methods: We searched the following 7 databases: 3 English medical databases (PubMed, EMBASE, Cochrane Library), and 4 Chinese medical databases (Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and the Wanfang database). The primary outcome was the effect of XFZYD combined with Mifepristone on the effective rate, uterine leiomyoma volume (ULV), and uterine volume (UV) of uterine leiomyoma. Bias risk was assessed using the Cochrane risk of bias tool. The software RevMan5 was used to evaluate the quality of the included studies and process the data.; Results: This study will evaluate the efficacy and safety of XFZYD combined with Mifepristone in the treatment of uterine fibroids by evaluating the effective rate, Uterine Leiomyoma volume, and uterine volume, the incidence of estradiol, luteinizing hormone, and other indicators.; Conclusion: This study will provide reliable evidence-based evidence for Xuefu Zhuyu Decoction Combined with Mifepristone in the treatment of uterine fibroids.; Ethics and Dissemination: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.; Osf Registration Number: DOI 10.17605/OSF.IO/YADN3.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Shi, S. Q., et al. (2020). "Comparison of pegylated liposomal doxorubicin and paclitaxel plus carboplatin-based chemotherapy as first line treatment for patients with ovarian cancer: a systematic review and meta-analysis of randomized controlled trials." European Review for Medical and Pharmacological Sciences 24(6): 2911-2927.
	We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with Pegylated Liposomal Doxorubicin (PLD) combination and those treated with paclitaxel combination for ovarian cancer. We conducted systematic searches in various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until August 2019. We used the Cochrane risk of bias tool to assess the quality of published trials. We carried out a meta-analysis with random-effects model and reported pooled Hazard ratios (HR) or Risk ratios (RR) with 95% confidence intervals (CIs). In total, we analysed 7 studies including 3,676 participants. All the studies were randomized controlled trials, while majority of studies had low bias risks. We did not find significant evidence for any of these outcomes except progression free survival (favoured PLD combination therapy pooled HR=0.87; 95% CI: 0.77-0.98). Worst grade toxicities like allergy (pooled RR: 1.86; 95% CI: 1.06-3.24) and neurotoxicity (pooled RR: 5.59; 95% CI: 1.43-21.84) were significantly higher among patients receiving paclitaxel combination therapy when compared to patients receiving PLD combination therapy. To summarize, PLD combination therapy is non-inferior to paclitaxel combination therapy in the management of ovarian cancer with respect to survival outcomes and worst grade toxicity profile. However, clinical recommendations cannot be made, as the evidence is not conclusive or significant enough.

Shi, T., et al. (2021). "Meta-analysis on aspirin combined with low-molecular-weight heparin for improving the live birth rate in patients with antiphospholipid syndrome and its correlation with d-dimer levels." Medicine 100(25): e26264.
	Background: Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer.; Methods: The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The "Risk of Bias Assessment" tool and the "Jadad Scale" provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software.; Results: In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22-1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09-1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results.; Conclusion: Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants.; Competing Interests: The authors report no conflicts of interest. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Shi, X.-Y., et al. (2020). "Effects of vitamin D supplementation on serum lipid profile in women with polycystic ovary syndrome: A protocol for a systematic review and meta-analysis." Medicine 99(23): e20621.
	Background: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in reproductive-aged women. In addition to the reproductive consequences, PCOS is also characterized by a metabolic disorder, which may play a part in the etiology of anovulation and has important implications for long-term health as well. Vitamin D deficiency is prevalent in PCOS and there is a close relationship between metabolic dysfunction and vitamin D status in women with PCOS. The purpose of this systematic analysis is to evaluate the effect of vitamin D supplementation on serum lipid profiles in patients with PCOS.; Methods: We will search five databases for relative studies: Medline, the Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov and identified all reports of randomized controlled trials published prior to July 2020. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model was used to calculate pooled estimates of weighted mean difference (WMD) with 95% confidence intervals.; Results: This review will be to assess the effect of vitamin D supplementation on serum lipid profiles in patients with PCOS. The results of the study will be published in a scientific journal after peer-review.; Conclusions: These findings will provide guidance to clinicians and patients on the use of vitamin D for PCOS with dyslipidemia.; Ethics and Dissemination: This study is a protocol for a systematic review of vitamin D as a treatment of dyslipidemia in PCOS patients.; Systematic Review Registration: INPLASY202050007.

Shi, Y., et al. (2020). "Effects of dairy products on bone mineral density in healthy postmenopausal women: a systematic review and meta-analysis of randomized controlled trials." Archives of osteoporosis 15(1): 48.
	Purpose: To investigate the effects of dairy products on bone mineral density (BMD) in healthy postmenopausal women.; Methods: The EMBASE, Cochrane Library, Medline, and Web of Science databases were systematically searched for relevant studies. The pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was used as the effect size. Subgroup analysis and Begg's test were conducted.; Results: Six studies with a total of 618 participants were included in the meta-analysis. Milk was the main dairy product used in the trials. There was a significant association between dairy product consumption and BMD of the lumbar spine (SMD 0.21, 95% CI 0.05-0.37, P = 0.009), femoral neck (SMD 0.36, 95% CI 0.19-0.53, P < 0.001), total hip (SMD 0.37, 95% CI 0.20-0.55, P < 0.001), and total body (SMD 0.58, 95% CI 0.39-0.77, P < 0.001). Subgroup analysis suggested that there was a positive effect of dairy product consumption on the BMD of the total hip starting from 12 months and the femoral neck starting from 18 months. There was also a positive association with the BMD in the four sites in people living in low-calcium intake countries.; Conclusion: This meta-analysis provides evidence that dairy products can increase BMD in healthy postmenopausal women. Dairy product consumption should be considered an effective public health measure to prevent osteoporosis in postmenopausal women.

Shi, Y., et al. (2022). "Application of Shaofu Zhuyu Decoction in hysteroscopic surgery for endometrial polyps and its effect on postoperative recurrence rate."  45(10): 2082‐2087.
	Objective To investigate the clinical effect of Shaofu Zhuyu Decoction in hysteroscopic surgery for patients with endometrial polyps and its effect on postoperative recurrence rate. Methods A total of 124 patients with endometrial polyps from June 2019 to January 2021 were selected as the subjects, and they were randomly divided into two groups with 62 cases in each group. Patients in the control group were treated with hysteroscopic surgery, antibiotics were routinely given to prevent infection after operation, and Progesterone Capsules were taken orally twice a day, 100 mg each time, for 15 days (one course of treatment) in the second half of the next menstrual cycle, i.e. the 15th day after menstruation. Patients in experimental group were treated with Shaofu Zhuyu Decoction for four weeks on the basis of the control group. After four weeks of medication, the patient's relevant indicators were evaluated and 12 months of follow‐up were completed. The time of symptom disappearance, endometrial thickness, plasma viscosity, fibrinogen, menstrual volume, pregnancy rate and recurrence rate of six and 12 months after treatment were compared between the two groups. Results After treatment, the disappearance time of menstruation increased, fatigue and weakness, five heart trouble, dimmish and darkish complexion, and abdominal pain symptoms in the experimental test group were significantly shorter than those in the control group (P < 0.05). After four weeks of treatment, the endometrial thickness, plasma viscosity, fibrinogen and menstrual volume of the two groups were significantly lower than those before treatment (P < 0.05). After four weeks of treatment, the endometrial thickness, plasma viscosity, fibrinogen and menstrual volume in the experimental group were significantly lower than those in the control group (P < 0.05). After 12 months of follow‐up, the pregnancy rate in the experimental group was significantly higher than that in the control group (P < 0.05), and the recurrence rate was significantly lower than that of the control group (P < 0.05). Conclusion The addition of Shaofu Zhuyu Decoction after hysteroscopy can significantly shorten the time of symptom disappearance in patients with endometrial polyps, improve the thickness of endometrium and the level of hemorheology, regulate the menstrual volume of patients, increase the pregnancy rate of patients, and reduce the recurrence rate, which is worth popularizing.

Shibata, M., et al. (2023). "EE500 Cost-Effectiveness Analysis of Cemiplimab As Second-Line Therapy for Recurrent Cervical Cancer in Japan." Value in Health 26(6 Supplement): S150-S151.
	Objectives: Patients with recurrent cervical cancer have a poor response to standard chemotherapy. Although cemiplimab, new anti-PD-1 drug, showed superiority over chemotherapy in improving overall survival, its cost-effectiveness is not necessarily clarified. This study aimed to evaluate the cost-effectiveness of cemiplimab for recurrent cervical cancer from the payer's perspective in Japan. Method(s): A partitioned survival analysis model was developed to predict costs and quality-adjusted life years (QALYs) in cemiplimab and chemotherapy group. Survival data were derived from the Phase-3 RCT. Drug prices for cemiplimab were estimated based on foreign prices. Cost parameters other than drug cost were estimated by using the JMDC claims database. Utilities were derived from previous studies. Lifetime horizon and discount rate of 2% was applied. The incremental cost-effectiveness ratio (ICER) of cemiplimab compared with chemotherapy was estimated. Sensitivity analyses were performed to assess heterogeneity and parameter uncertainty. Result(s): Cemiplimab incurred an additional cost of 12,476,074 and conferred an additional 0.581 QALY. This resulted in the ICER of 21,472,662 per QALY gained. Subgroup analyses showed the ICER was JPY20,554,164/QALY and JPY19,647,357/QALY in squamous-cell carcinoma and adenocarcinoma, respectively. Deterministic sensitivity analysis indicated that Utility of cemiplimab in progression state had the greatest impact on base case. The ICER ranged from JPY17,853,048 to JPY21,842,638/QALY. The ICERs remained higher than JPY15 million/QALY over the full range of model parameters. Conclusion(s): Applying the willingness to pay threshold of JPY15 million/QALY, cemiplimab therapy was not cost-effective. Further research is required on utilities of Japanese patients with recurrent cervical cancer.Copyright © 2023

Shifrin, G., et al. (2021). "Transcervical Fibroid Ablation with the Sonata System for Treatment of Submucous and Large Uterine Fibroids." Journal of Minimally Invasive Gynecology 28(11 Supplement): S152.
	Study Objective: To examine the role and benefits of transcervical fibroid ablation (TFA) in the treatment of submucous and large uterine fibroids. Design(s): Subgroup analysis of two multicenter, prospective, controlled trials. Setting(s): Academic and community hospitals in the UK, the Netherlands, the US and Mexico. Patients or Participants: 197 women who underwent TFA with the Sonata System within the FAST-EU and SONATA clinical trials. Intervention(s): TFA was used to ablate fibroids under clinical trial protocol. Measurements and Main Results: Key outcomes were changes in menstrual blood loss, symptom severity and health-related quality of life on the Uterine Fibroid Symptom and Quality-of-Life Questionnaire, health-related quality of life on the EQ-5D questionnaire, and surgical reinterventions for heavy menstrual bleeding. Among 197 women (with 534 treated fibroids), 86% of women with only submucous fibroids and 81% of women with large fibroids (>5 cm) experienced bleeding reduction within 3 months post-ablation. Overall symptom severity and health-related quality of life showed sustained, significant improvements over 12 months. Additional fibroid mapping of large fibroids with magnetic resonance imaging in the FAST-EU trial showed an average volume reduction of 68%. Among women with only submucous fibroids, the rate of surgical reintervention through 1 year of follow up was 3.7% in FAST-EU and 0.0% in SONATA. Conclusion(s): With the Sonata System, TFA is an effective single-stage treatment option for non-pedunculated submucous myomata, and larger or deeper uterine fibroids (including fibroid clusters) for which hysteroscopic treatment is not suitable.Copyright © 2021

Shim, J. Y., et al. (2024). "Evaluation and Management of Endometriosis in the Adolescent." Obstetrics and Gynecology 143(1): 44-51.
	Endometriosis is a chronic condition, with debilitating symptoms affecting all ages. Dysmenorrhea and pelvic pain often begin in adolescence, affecting school, daily activities, and relationships. Despite the profound burden of endometriosis, many adolescents experience suboptimal management and significant delay in diagnosis. The symptomatology and laparoscopic findings of endometriosis in adolescents are often different than in adults, and the medical and surgical treatments for adolescents may differ from those for adults as well. This Narrative Review summarizes the diagnosis, evaluation, and management of endometriosis in adolescents. Given the unique challenges and complexities associated with diagnosing endometriosis in this age group, it is crucial to maintain a heightened level of suspicion and to remain vigilant for signs and symptoms. By maintaining this lower threshold for consideration, we can ensure timely and accurate diagnosis, enabling early intervention and improved management in our adolescent patients.Copyright © 2024 Lippincott Williams and Wilkins. All rights reserved.

Shin Ja, H., et al. (2020). "Transversus Abdominis Plane Block for Laparoscopic Hysterectomy Pain: A Meta-Analysis." JSLS : Journal of the Society of Laparoendoscopic Surgeons 24(2).
	Objective: Review the analgesic effect of the transversus abdominis plane (TAP) block and its impact on postoperative pain scores and opioid usage for patients undergoing laparoscopic and robotic hysterectomies.; Methods: Systematic review with meta-analysis of randomized controlled trials that compared the effect of TAP block to either placebo or no block on narcotic use (in morphine equivalent units [MEq]) and pain (per visual analog scale) within 24] h after a laparoscopic or robotic hysterectomy for benign or malignant indications. Searches were conducted in PubMed and Embase through May 31, 2019.; Results: Nine randomized controlled trials met eligibility criteria; 7 evaluated laparoscopic hysterectomy and 2 robotic hysterectomy. A total of 688 subjects were included (559 laparoscopic hysterectomy, 129 robotic hysterectomy). Opioid consumption was similar in the first 24] h postoperative with or without TAP block (-0.8 MEq; 95% CI, -2.9, 1.3; 8 TAP arms; N] = 395). Pain scores (visual analog scale) were also similar with or without TAP block (-0.01 U; 95% CI, -0.34, 0.32; 10 TAP arms; N] = 636). Neither meta-analysis showed statistical heterogeneity across studies.; Conclusions: The evidence does not support a benefit of TAP block to reduce pain or opioid use for patients receiving laparoscopic or robotic hysterectomies.; Competing Interests: Disclosure of Conflicts of Interest and Sources of Financial Support: JS, none; EMB, none; KG, Consultant for Avanos; AW, none; KP, none; NS, Advisory Board & Consultant for Averitas Pharma & AcelRx Pharmaceuticals, Research Grants/Clinical Trials from Grunenthal & Heron Therapeutics. (© 2020 by JSLS, Journal of the Society of Laparoscopic & Robotic Surgeons.)

Shinozaki, K., et al. (2022). "Postpartum urinary incontinence and birth outcomes as a result of the pushing technique: a systematic review and meta-analysis." International Urogynecology Journal 33(6): 1435-1449.
	Introduction and hypothesis: Directed pushing while using the Valsalva maneuver is shown to lead to bladder neck descent, especially in women with urinary incontinence (UI). There is insufficient evidence about the benefits or adverse effects between the pushing technique during the second stage of labor and urinary incontinence postpartum. The objective of this study was to evaluate the effects of the pushing technique for women during labor on postpartum UI and birth outcomes. Method(s): Scientific databases were searched for studies relating to postpartum urinary incontinence and birth outcomes when the pushing technique was used from 1986 until 2020. RCTs that assessed healthy primiparas who used the pushing technique in the second stage of labor were included. In accordance with Cochrane Handbook guidelines, risk of bias was assessed and meta-analyzed. Certainty of evidence was assessed using the GRADE approach. Result(s): Seventeen RCTs (4606 primiparas) were included. The change in UI scores from baseline to postpartum was significantly lower as a result of spontaneous pushing (two studies; 867 primiparas; standardized mean difference: SMD -0.18, 95% CI -0.31 to -0.04). Although women were in the recumbent position during the second stage, directed pushing group showed a significantly shorter labor by 21.39 min compared with the spontaneous pushing group: there was no significant difference in the duration of the second stage of labor between groups. Conclusion(s): Primiparas who were in the upright position and who experienced spontaneous pushing during the second stage of labor could reduce their UI score from baseline to postpartum.Copyright © 2021, The Author(s).

Shiva, P., et al. (2021). "Heavy menstrual bleeding and pelvic pain in adolescents: self-management strategies, quality of life and unmet needs."
	
Shojaeian, Z., et al. (2019). "Calcium and Vitamin D supplementation effects on metabolic factors, menstrual cycles and follicular responses in women with polycystic ovary syndrome: A systematic review and meta-analysis." Caspian journal of internal medicine 10(4): 359-369.
	Background: Polycystic ovary syndrome (PCOS) is the most popular endocrine disorder in reproductive age with unknown etiology and many comorbidities. This systematic review focused on the effectiveness of calcium and Vitamin D (Ca/ Vit.D) supplementation on metabolic factors, menstrual cycles, and follicular responses in PCOS patients. Method(s): Relevant studies were identified from the following electronic databases including Pub Med, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, issue Oct. 2018, Evidence Based Medicine Reviews (EBMR), Google Scholar, EMBASE, as well as Farsi databases including Magiran and SID from 2000 to 2018. Out of 449 articles, six clinical trials met the inclusion criteria. Result(s): Out of six studies included in the study, only three studies had sufficient data for meta-analysis. Overall, studies showed that prescribing Ca/ Vit. D supplementation with metformin improved menstrual regularity and follicular maturation and significant decreases in serum insulin levels, homeostasis model of assessment-insulin resistance (HOMA-IR) and fasting blood sugar (FBS) and also significant rises on quantitative insulin sensitivity check index (QUICKI) at two studies. Hirsutism and level of testosterone decreased significantly after adding Ca/ Vit. D to metformin in two different studies. Based on two different trials, co-supplementation of Ca/ Vit. D had a significant impact to decrease serum triglycerides and VLDL-cholesterol levels as well as levels of cholesterol and LDL. Conclusion(s): It is possible that calcium and Vitamin D supplementation improve menstrual disturbances and metabolic factors in PCOS in a long-term period, but further trials are still needed to confirm these findings.Copyright © 2019 Babol University of Medical Sciences. All rights reserved.

Shokri, P., et al. (2023). "A systematic review and meta-analysis of complications of artificial urinary sphincters in female patients with urinary incontinence due to internal sphincter insufficiency." BMC Urology 23(1): 97.
	Background: Urinary incontinence (UI) is a common worldwide rising health issue among women with a prevalence of 5 to 70%. Stress urinary incontinence (SUI) is the most common subtype of UI. There are different treatments for UI, including AUS (artificial urinary sphincter) implantation, as one of the surgical options for treating SUI. The aim of this study was to determine the complication rate of AUS, exclusively in female patients with SUI, which resulted from ISD (intrinsic sphincter deficiency). We also compared the complication rate between minimally invasive (laparoscopic or robotic surgery) and open approaches. Method(s): Scopus, PubMed, Web of Science, Embase, and Google Scholar were searched for studies regarding complications in AUS implantation surgery, from the beginning of the project to March 2022. After screening and reviewing of full text, the general characteristics of the study and study population including follow-up time, type of surgery, and the number of complications that occurred such as necrosis, atrophy, erosion, infection, mechanical failure, revision, and leak, were extracted. Result(s): We found that atrophy occurred in 1 of 188 (0.53%) patients treated with minimally invasive surgery and in 1 of 669 (0.15%) patients treated with open surgery. None of the 17 included studies reported the occurrence of necrosis in the patients under study. Erosion occurred in 9 of 188 (4.78%) patients treated with minimally invasive surgery and in 41 of 669 (6.12%) patients treated with open surgery. Infection occurred in 12 of 188 (6.38%) patients treated with minimally invasive surgery and in 22 of 669 (3.2%) patients treated with open surgery. The mechanical failure occurred in 1 of 188 (0.53%) patients treated with minimally invasive surgery and in 55 of 669 (8.22%) patients treated with open surgery. Reconstructive surgery occurred in 7 of 188 (3.72%) patients treated with minimally invasive surgery and in 95 of 669 (14.2%) patients treated with open surgery. Leaks occurred in 4 of 188 (2.12%) patients treated with minimally invasive surgery and in 6 of 669 (0.89%) patients treated with open surgery. The type of surgery was associated with a statistically significant increase in mechanical failure (p-value = 0.067) and infection (p-value = 0.021), and reconstructive surgery (p-value = 0.049). Out of the 857 participats in the study,469 were studied for less than five years and 388 were studied for more than five years.21 of 469 (4.4%) (p-value = 0.08) patients and 81 of 388 (20.8%) (p-value = 0.001) patients required reconstructive surgery. Erosion occurred in 23 of 469 (4.9%) (p-value = 0.01)patients with following time less than five years and in 27 of 388 (6.9%) (p-value = 0.001) patients with following time more than five years. Conclusion(s): The use of artificial urinary sphincters in the treatment of UI causes complications such as atrophy, erosion, and infection; the amount of which is influenced by the surgical method and the duration of using the artificial urinary sphincter. It seems that the use of new surgical methods, such as laparoscopic surgery, is useful in reducing the incidence of complications.Copyright © 2023, The Author(s).

Shokri-Ghadikolaei, A., et al. (2022). "Effects of health coaching on menopausal symptoms in postmenopausal and perimenopausal women." Menopause (New York, N.Y.) 29(10): 1189-1195.
	Objective: This study aimed to determine the effects of health coaching on reducing menopausal symptoms in postmenopausal and perimenopausal women.; Methods: This randomized controlled study was performed on 94 postmenopausal and perimenopausal women aged 45 to 55 years. The participants were randomly divided into intervention and control groups. In the intervention group, health coaching was performed in five coaching sessions biweekly (30-45 minutes each) by a midwifery coach. The primary outcome of this study was the menopausal score based on the modified Kupperman Index at 4 months after randomization. Depression (based on Zung's Self-Rating Depression Scale), physical activity (based on the International Physical Activity Questionnaire), quality of life (based on the 12-Item Short-Form Survey), smoking, alcohol intake, and anthropometric indices were also evaluated as secondary outcomes.; Results: There was a significant mean difference between the coaching and control groups in terms of change in the scores of menopausal symptoms from baseline (T0) to 4 months after the intervention (T1; -12.51; 95% confidence interval [CI], -10.59 to -14.42; P = 0.001). Moreover, a significant mean difference was observed between the two groups in terms of change in depression symptoms from T0 to T1 (-5.72; 95% CI, -7.61 to -3.83; P < 0.001) and in terms of quality of life (4.13; 95% CI, 2.95 to 5.31; P < 0.001). Health coaching, however, had no effects on the physical activity of the participants.; Conclusion: Based on the present results, the coaching intervention is a suitable method to improve quality of life by reducing weight, waist circumference, body mass index, depression, and menopausal symptoms in postmenopausal and perimenopausal women. It can have important effects on the development of health promotion programs to reduce menopausal symptoms in menopause clinics.; Competing Interests: Financial disclosure/conflicts of interest: Babol University of Medical Sciences provided all funding sources (grant numbers: 724132700). (Copyright © 2022 by The North American Menopause Society.)

Shortis, E., et al. (2020). "The efficacy of cognitive behavioral therapy for the treatment of antenatal depression: A systematic review." Journal of Affective Disorders 272: 485-495.
	Background: Antenatal depression affects 7-20% of pregnant women globally yet less than a fifth of such women receive adequate treatment. Cognitive behavioral therapy (CBT) is known to be effective in the treatment of depression. However, the research is more limited with regard to the antenatal period suggesting a need for clearer evidence within this field. Objective(s): To determine if CBT is effective in the treatment of antenatal depression. Method(s): Medline, Embase, PsychINFO, CINAHL and CENTRAL were searched for studies that quantified the effectiveness of CBT in women with a confirmed diagnosis of antenatal depression. Randomised controlled trials that measured the effectiveness of CBT delivered during the antenatal period, compared to another intervention or usual care, measured using a validated depression score pre and post intervention were included. Result(s): Five RCTs were eligible for inclusion, all of which found a significant decrease in depression scores following CBT interventions, greater than that observed in control groups. Improvements in depressive scores were maintained long-term for participants who received CBT. Participant satisfaction with the interventions received was high. Limitation(s): Studies included displayed major performance biases, and language bias is present due to exclusion of an Iranian paper. Conclusion(s): CBT, tailored to pregnant women, is effective in the treatment of antenatal depression, with little difference in efficacy between CBT sub-types. Further large-scale RCTs are needed to confirm these hypotheses and determine the most cost-effective way of delivering CBT to pregnant women. There is also need for a specific, validated tool for assessing antenatal depression.Copyright © 2020

Shrestha, D. B., et al. (2022). "Vesico-Vaginal Fistula in Females in 2010-2020: a Systemic Review and Meta-analysis." Reproductive Sciences 29(12): 3346-3364.
	Introduction: In the Western world today, urogenital fistula, including vesicovaginal fistula (VVF), is rare. However, while it remains significant in developing parts of the world due to prolonged and obstructed labor, in this study, we systematically reviewed the existing literature, discussing VVF occurrence, its etiology, and outcomes. Material(s) and Method(s): We used electronic databases to search relevant articles from 2010-2020. The screening was performed with the help of Covidence. Relevant data from included studies were extracted in excel sheets, and final analysis was done using CMA-3 using proportion with 95% confidence interval (CI). Result(s): Fifteen studies reported the VVF among the fistula series. The pooled result showed 76.57% cases of VVF (CI, 65.42-84.96), out of which 27.54% were trigonal, 55.70% supra-trigonal, and the rest with a varied description like circumferential, juxta-cervical, juxta-urethral. Obstetric etiology was commonly reported with 19.29% (CI, 13.26-27.21) with cesarean section and 31.14% (CI, 18.23-47.86) with obstructed labor. Hysterectomy was the commonly reported etiology among gynecological etiology (46.52%, CI; 36.17-57.19). Among different surgical treatments employed for fistula closure, 49.50% were by abdominal approach (CI, 37.23-61.82), and 42.31% by vaginal approach (CI, 31.82-53.54). Successful closure of fistula was reported in 87.09% of the surgeries (CI, 84.39-89.38). Conclusion(s): The vesicovaginal fistula is the most common type of genitourinary fistula. Major causes of fistula are gynecological surgery, obstructed labor, and cesarean section. The vaginal approach and abdominal are common modalities of repair of fistula with favorable outcomes in the majority of the patients.Copyright © 2021, Society for Reproductive Investigation.

Shuai, G., et al. (2023). "Durable effects of acupuncture for chronic prostatitis/chronic pelvic pain syndrome:a systematic review and meta-analysis."
	
Shuang, H., et al. (2021). "Outcome comparison of intermittent catheterization and retention catheterization in Chinese patients after radical resection of cervical cancer: a systematic review and meta-analysis of randomized controlled trials."
	
Shuangshuang, Z., et al. (2023). "Oncologic and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection."
	
Shucheng, C., et al. (2022). "Traditional Chinese medicine interventions based on meridian theory for primary dysmenorrhea: A systematic review and network meta-analysis."
	
Shujuan, M. and P. Yangqin (2021). "Fertility Outcomes of Single Embryo and Double Embryo Transfer - A Systematic Review and Meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Shumin, H., et al. (2023). "Efficacy of warm needle acupuncture for the treatment of thin endometrium: a systematic review and meta-analysis."
	
Shuo, Y., et al. (2021). "The Effect of Oral Antidiabetic Drugs for Improving the Endocrine and Metabolic Profile in Women with Polycystic Ovary Syndrome: A Systematic Review and Network Meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Shuting, W., et al. (2021). "Integrated Traditional Chinese and Western medicine in the treatment of polycystic ovary syndrome: a systematic review and meta-analysis."
	
Shuting, Z. and L. Xian (2023). "Effects of perioperative care on psychological and quality of life in cancer patients: a systematic review and a case-study analysis."
	
Shwe, S., et al. (2022). "Mohs micrographic surgery for vulvar malignancies: A systematic review." Journal of the American Academy of Dermatology 87(1): 159-162.
	Competing Interests: Conflicts of interest None disclosed.

Shyamoli, C., et al. (2021). "Psychological intervention for sexual dysfunction in women with urogenital incontinence."
	
Si, Y., et al. (2020). "Effectiveness and safety of Guilu Erxian Glue (a traditional Chinese medicinal product) for the treatment of postmenopausal osteoporosis: A protocol for systematic review and meta-analysis." Medicine (United States) 99(29): E20773.
	Background:The prevalence of postmenopausal osteoporosis is rapidly rising, with a high proportion of patients who are vulnerable to fractures and other chronic symptoms. The commonly applied Western medicine lacks cost-efficiency and tends to have various potential side effects. Guilu Erxian Glue (GEG), an orally taken traditional Chinese medicinal product, has been advocated to manage osteoporosis for a long period. However, the evidence of the efficacy of GEG on osteoporosis seems to be less convincing and conclusive. Therefore, the purpose of this study is to assess the effectiveness and safety of GEG on postmenopausal osteoporosis. Method(s):We will implement a systematic review and meta-analysis following the requests of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). The PubMed database, Scopus, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP database, Sinomed, and grey literature sources will be retrieved for eligible studies. Randomized controlled trials investigating GEG in women with postmenopausal osteoporosis employing osteoporosis-associated outcomes measures will be eligible for inclusion. Two reviewers will independently complete the study selection procedure, data extraction, and risk of bias assessment. A third reviewer will mediate when irreconcilable discrepancies occur. Should sufficient clinical homogeneity exist, a meta-analysis will be conducted. Additionally, we will utilize the Grading of Recommendations Assessment, Development and Evaluation to assess the strength of quantitative outcomes. Result(s):The current systematic review and meta-analysis will provide the effectiveness and safety of GEG on postmenopausal osteoporosis. Conclusion(s):The study will offer high-quality and explicit evidence for applying GEG on the treatment of postmenopausal osteoporosis.OSF Registration:DOI 10.17605/OSF.IO/JCVBH.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Siblini, H., et al. (2021). "EPIGALLOCATECHIN GALLATE (EGCG) FOR TREATMENT OF UNEXPLAINED INFERTILITY ASSOCIATED WITH UTERINE FIBROIDS (PRE-FRIEND TRIAL): EARLY SAFETY ASSESSMENT." Fertility and Sterility 116(3): e318‐e319.
	Objective: Uterine fibroids are the most common pathology associated with unexplained infertility in reproductive aged women worldwide. Compared with women without fibroids, women with intramural and submucosal fibroids have a decreased likelihood of pregnancy. Surgical removal of fibroids is commonly offered, but are associated with postoperative adhesions and fibroid recurrence, so the net fertility gain is often compromised. Thus, there is a crucial need for innovative, non‐hormonal and non‐surgical fertility treatment options for women with fibroids and infertility. Epigallocatechin gallate (EGCG), a green tea catechin, has proven to induce apoptosis and shrink uterine fibroids in preclinical animal models as well as in a randomized clinical trial. Recently we have developed the NICHD ConFIRM funded trial to evaluate the utility of EGCG to treat women with unexplained infertility associated with uterine fibroids (FRIEND trial). Before embarking on the FRIEND trial, it was considered prudent to first conduct the Pre‐FRIEND study to evaluate the safety of EGCG in premenopausal women. Specifically, we aimed to assess any adverse effects of EGCG or combination therapy with an ovulation stimulator on serum liver function tests (LFTs) and folate levels. Materials and Methods: Pre‐FRIEND (NCT 04177693) is a randomized open‐label prospective cohort study to enroll 36 women ages ≥18 to ≤40 years with/without uterine fibroids. Participants are recruited from the FRIEND Collaborative clinical sites: Johns Hopkins University, University of Chicago, University of Illinois at Chicago, and Yale University. Randomization is stratified by age (18‐29, 30‐40) and presence of fibroids. Subjects are randomized to one of 3 treatment arms: 800mg of EGCG daily alone, 800mg of EGCG daily with clomiphene citrate 100mg for 5 days, or 800mg of EGCG daily with Letrozole 5mg for 5 days. The study involves 5 visits in total through which safety serum labs are followed including: folate, estradiol, and detailed LFTs. To determine potential drug induced liver injury (DILI), Hy’s law has been adopted which defines DILI as serum ALT or AST elevation >3x the upper limit of normal (ULN), total bilirubin levels > 2x the ULN and no other reason to explain it. For the comparison of serum liver function tests and folate levels among these different groups, ANOVA (unadjusted) and multivariate linear regression are used. Results: This is an active ongoing study. At time of submission, 14 subjects have been recruited, and 8 have successfully completed the study. Screen failure rate was 7% (N=1). No subject has fulfilled Hy’s DILI criteria. No subject showed serum folate levels outside the normal range and no subject reported any serious drug‐related adverse events. Conclusions: At present our data suggest that a daily dose of 800mg of EGCG alone or in combination with clomiphene citrate or letrozole (5 days) is well tolerated and is not associated with liver toxicity or folate deficiency in reproductive age women. Impact Statement: EGCG alone or in combination with Clomiphene citrate or Letrozole demonstrates good safety profile in reproductive age women.

Sicardo, J., et al. (2022). "The Influence of Therapeutic Exercise on Survival and the Quality of Life in Survivorship of Women with Ovarian Cancer." International Journal of Environmental Research and Public Health 19(23).
	Background: Ovarian cancer is the most difficult of all gynaecological cancers to treat, mainly due to its late diagnosis. Although exercise interventions have been reported to be safe and beneficial for ovarian cancer, treatment does not include it and is usually a combination of chemotherapy and surgery. It is increasingly common to include exercise as a tool to increase survival in the cancer population. The aim of this study was to determine the influence of therapeutic exercise on survival and the quality of life in survivorship in women with ovarian cancer.; Methods: Literature review of clinical trials, reviews and pilot studies compiled in three databases collected in PubMed, PEDro and Scopus.; Results: Of the 44 articles found, 10 were selected. Improvements in survival, quality of life and comorbidities associated with ovarian cancer were found with exercise interventions as a treatment tool.; Conclusions: Through the application of therapeutic exercise, improvements in survival and quality of life were observed, as well as in the general symptomatology of ovarian cancer. No adverse effects have been found with its use, but future studies with larger sample sizes with more detailed and individualised interventions combined with conventional treatment are needed.

Siddiqui Raheel, S. and M. Sardar (2021). "A Systematic Review of the Role of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in the Treatment of Solid Tumors." Cureus 13(4): e14494.
	Chimeric antigen receptor T (CAR-T) cell therapy utilizes patients' own T lymphocytes that are engineered to attack cancer cells. It is Food and Drug Administration (FDA)-approved in various hematological malignancies and currently being evaluated in solid cancers in early phase studies. We did a systematic review consisting of 15 prospective clinical trials (n=159) evaluating CAR-T cells in solid cancers. Early phase trials showed promising response rates in ovarian epithelial cancer (100%), human epidermal growth factor receptor 2 (HER2)-positive sarcoma (67%), epidermal growth factor receptor (EGFR)-positive biliary tract cancer (65%), advanced gastric/pancreatic cancer (82%), hepatocellular carcinoma (67%), and colorectal cancer (70%). The median overall response across all malignancies was 62% (range 17%-100%). Median progression-free survival and overall survival were not reached in most trials. Cytokine release syndrome was seen in only one patient with cholangiocarcinoma who received EGFR-specific CAR-T cell therapy. Although survival data is still not mature, CAR-T cell therapy in solid malignancies did show encouraging response rates and was well-tolerated.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2021, Siddiqui et al.)

Sidik, S. M., et al. (2021). "KEPT-app trial: a pragmatic, single-blind, parallel, cluster-randomised effectiveness study of pelvic floor muscle training among incontinent pregnant women: study protocol." BMJ Open 11(1): 039076.
	Introduction Pelvic floor muscle training (PFMT) strongly recommended to incontinent pregnant women. The Kegel Exercise Pregnancy Training-app trial is a multicentre cluster-randomised study aims to assess the effectiveness and its cost-effectiveness of the mobile app guidance in PFMT among incontinent pregnant women. Methods and analysis 370 pregnant women (aged 18 years old and above) will be recruited with International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form. Ten clusters (primary care clinics) will be randomly assigned to either PFMT or usual care in a 1:1 ratio by an independent researcher (sealed envelope). The primary outcome will be urinary incontinence, and the secondary outcomes (quality of life; PFMT adherence, psychological status and mobile apps' usability) will be assessed at four measurement time points (t0: baseline) and postintervention (t1: 4 weeks, t2: 8 weeks and t3: 8 weeks postnatal). T-test analysis will determine any significant differences at the baseline between the control and intervention groups. The mixed-model analysis will determine the effectiveness of the intervention at the population-average level for both the primary and secondary outcomes. For the cost-effectiveness analysis, expenditures during the study and 6 months after the intervention will be compared between the groups using the multiway sensitivity analysis. The recruitment planned will be in December 2020, and the planned end of the study will be in August 2021. Ethics and dissemination This study protocol was approved by the Ethics Committee for Research Involving Human Subjects, Universiti Putra Malaysia (JKEUPM-2019-368) and Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia, NMRR-19-412-47116 (IIR) with the ANZCTR registration. This study will obtain informed written consent from all the study participants. The results which conform with the Consolidated Standards of Reporting Trials and the Recommendations for Interventional Trials will be published for dissemination in peer-reviewed journals and conference proceedings. Trial registration number ACTRN12619000379112.Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Siegenthaler, F., et al. (2022). "Prospective Multicenter Trial Assessing the Impact of Positive Peritoneal Cytology Conversion on Oncological Outcome in Patients with Endometrial Cancer Undergoing Minimally Invasive Surgery with the use of an Intrauterine Manipulator : Positive Peritoneal Cytology Conversion and Its Association with Oncological Outcome in Endometrial Cancer." Annals of Surgical Oncology 29(13): 8320-8333.
	Background: Minimally invasive surgery is the standard approach in early-stage endometrial cancer according to evidence showing no compromise in oncological outcomes, but lower morbidity compared with open surgery. However, there are limited data available on the oncological safety of the use of intrauterine manipulators in endometrial cancer.; Patients and Methods: This prospective multicenter study included patients with endometrial cancer undergoing laparoscopic staging surgery with the use of an intrauterine manipulator. We obtained three different sets of peritoneal washings: at the beginning of the surgical procedure, after the insertion of the intrauterine manipulator, and after the closure of the vaginal vault. The rate of positive peritoneal cytology conversion and its association with oncological outcomes was assessed.; Results: A total of 124 patients were included. Peritoneal cytology was negative in 98 (group 1) and positive in 26 (group 2) patients. In group 2, 16 patients presented with positive cytology at the beginning of the surgery (group 2a) and 10 patients had positive cytology conversion during the procedure (group 2b). Recurrence rate was significantly different among the study groups, amounting to 9.2%, 25.0%, and 60.0% for groups 1, 2a, and 2b, respectively (p < 0.001). Group 1 showed the best recurrence-free and overall survival, followed by group 2a, while patients in group 2b had the worst oncological outcomes (p = 0.002 and p = 0.053, respectively). Peritoneal cytology was an independent predictor of recurrence and death on multivariable analysis.; Conclusion: A total of 8.1% of patients with endometrial cancer undergoing minimally invasive surgery with intrauterine manipulation showed positive peritoneal cytology conversion associated with significantly worse oncological outcome. (© 2022. The Author(s).)

Sigurdardottir, T., et al. (2022). "Pelvic organ prolapse and postpartum pelvic floormuscle training. A randomized controlled trial of primiparous women." International Urogynecology Journal 33(Supplement 1): S59-S60.
	Introduction: Pelvic floor dysfunction, including pelvic organ prolapse (POP), is a common and bothersome postpartum complaint, likely to reduce quality of life. Objective(s): To study the effects of individualized physical therapistguided pelvic floor muscle training (PFMT) in the early postpartum period on POP and related bother, as well as pelvic floor muscle (PFM) strength and endurance. Method(s): This was an assessor-blinded, randomized controlled trial starting 9 weeks after childbirth. Primary outcomes were rates of POP and bother. PFM strength and endurance were secondary outcomes. Between 2016-2017, 84 primiparous women entered the trial, involving 12 weekly sessions with a physical therapist. The outcomes were assessed within a week after the last session (short-term) and at 12 months postpartum( long-term). The control group (CG) received no instructions after the initial assessment. POP was defined as self-reported sensation of protrusion/bulging and/or experiencing vaginal pressure or heaviness. Chi-squared test was used to test differences in between-groups rates of women and McNemar's test for differences in changes between groups regarding symptoms of POP and bother, while independent sample t-tests were used to assess mean differences in muscle strength and endurance. Significance levels were set as =0.05. Result(s): Forty-one and 43 women were randomized to the training group (TG) and CG, respectively. Three and one participants withdrew from the respective groups. At recruitment, 17 (42.5%) of the TG and 15 (37%) of the CG reported symptoms of pelvic organ prolapse (p=0.6) with 5 (13%) from the TG and 9 (21%) of the CG bothered by the symptoms (p=0.3). Short-term results showed that changes in POP rates measured from baseline to 6 months postpartum was in favor of the control group (p=0.02) with 20.5% vs. 29% reduction in the number of symptomatic women in the training and control group, respectively. The mean differences between groups in measured PFM strength changes evaluated immediately after the treatment was 5 hPa (95%CI 2-8; p=0.003), and for PFM endurance changes, 50 hPa/sec (95%CI 23-77; p=0.001), both in favor of the training group. Changes in the rates of women with POP measured from baseline to 12 months postpartum was 32% vs. 23%, (p<0.001) for the TG vs. the CG. There were no significant differences regarding the changes in rates of women bothered by symptoms with 10% and 14% reduction in rates for TG and CG respectively (p=0.3). PFM strength and endurance favoring the TG were maintained at 12 months postpartum. Conclusion(s): Postpartum symptoms of pelvic organ prolapse and bother decreased considerably during the first year for both controls and exercisers. Short-term results favoring the control group were overturned and at 12 months were in favor of the training group. There was a statistically significant long-termeffect in change of POP symptoms after PFMT. The results might have been subjected to type II error.

Silk Ann, W., et al. (2022). "A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors." European journal of medical research 27(1): 107.
	Background: Glutamate signaling activates MAPK and PI3K/AKT pathways in tumor cells. Treatment with riluzole, a glutamate release inhibitor, has been previously shown to be safe in melanoma patients and produced biologic effects, but did not lead to radiographic responses, possibly due to poor pharmacokinetic properties. Therefore, we conducted a phase Ib trial to determine the safety and tolerability of the combination of the riluzole prodrug troriluzole (BHV-4157, trigriluzole) and the PD-1 antibody nivolumab in patients with advanced solid tumors.; Methods: Patients with advanced or refractory solid tumors and measurable disease per RECIST 1.1 were treated with increasing doses of troriluzole using a semi-Bayesian modified toxicity probability interval dose escalation procedure. Troriluzole monotherapy was orally self-administered for a 14-day lead-in period followed by continuation of troriluzole in combination with nivolumab 240 mg IV every 2 weeks. Endpoints included safety, pharmacokinetics (PK) and efficacy.; Results: We enrolled 14 patients with advanced solid tumors (melanoma = 3, NSCLC = 3, renal cell carcinoma = 2, bladder/urothelial = 2, ovarian cancer = 1, adenoid cystic carcinoma = 1, pleural mesothelial = 1, head and neck cancer = 1). Eleven patients had cancer progression on prior therapy with PD-1 or PD-L1 agent. Patients received troriluzole total daily doses from 140 to 560 mg (divided). The most common treatment-related adverse events (TRAE) occurring in ≥ 5 patients (> 35%) were transaminitis and increased lipase. DLT (dose-limiting toxicity) occurred in 3 patients: (1) grade 3 anorexia, (2) grade 3 fatigue and, (3) grade 3 atrial fibrillation. Six patients were treated at the MTD (maximum tolerated dose). No subjects discontinued treatment due to AEs. One response occurred (7%), which was a partial response in a subject who had PD-1 refractory disease. The 6-month PFS rate was 21%. PK data showed that the prodrug troriluzole was efficiently cleaved into riluzole by 2-h post-dosing in all dose cohorts tested.; Conclusion: The combination of troriluzole and nivolumab was safe and well-tolerated. The MTD of troriluzole was determined to be 420 mg total daily dose. The observed antitumor activity, primarily disease stabilization, is of interest in patients with PD-1 resistant tumors. Trial Registration ClinicalTrials.gov Identifier NCT03229278. (© 2022. The Author(s).)

Silva, T., et al. (2022). "Efficacy and safety of electrical stimulation in the treatment of neurogenic bladder dysfunction in myelomeningocele-Systematic review of randomized clinical trials." Neurourology and Urodynamics 41(1): 91-101.
	Aims: The purpose of this systematic review was to investigate and synthesize the effects (benefits and harms) of electrical stimulation (EE), alone or in association with other interventions, compared with sham and other interventions, for the treatment of neurogenic bladder dysfunction in myelomeningocele. Method(s): This systematic review was conducted following the methodological recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and registered at PROSPERO (CRD42020200425). A search was performed in the following electronic databases: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, LILACS, and PEDro. Randomized clinical trials (RCTs) that assessed any EE in children diagnosed with myelomeningocele and neurogenic bladder and/or urinary incontinence were included and reported. Result(s): When comparing EE versus sham groups, some estimated effects showed a wide confidence interval, probably due to the small sample size of the included studies. This indicates an imprecision in these findings. Regarding the safety of this intervention and safety of the lower urinary tract, no adverse events resulting from EE were reported. All the included studies have evaluated the efficacy of EE compared with sham, but different EE parameters and electrode positions among studies make it impossible to perform a meta-analysis. Conclusion(s): Based on very low certainty evidence, the findings of this systematic review suggested no difference between EE and sham to improve urinary incontinence in children with myelomeningocele. However, the small sample size and the imprecision arising from the wide confidence intervals must be considered. Future RCTs following a rigorous methodology, as recommended by the CONSORT statement, should be conducted to support the use of this intervention in clinical practice.Copyright © 2021 Wiley Periodicals LLC

Silva Thiago Menezes, d., et al. (2023). "Efficacy, Safety, and Acceptability of Misoprostol in the Treatment of Incomplete Miscarriage: A Systematic Review and Meta-analysis." Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia 45(12): e808-e817.
	Objective: To assess the efficacy, safety, and acceptability of misoprostol in the treatment of incomplete miscarriage.; Data Sources: The PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Clinical Trials databases (clinicaltrials.gov) were searched for the relevant articles, and search strategies were developed using a combination of thematic Medical Subject Headings terms and text words. The last search was conducted on July 4, 2022. No language restrictions were applied.; Selection of Studies: Randomized clinical trials with patients of gestational age up to 6/7 weeks with a diagnosis of incomplete abortion and who were managed with at least 1 of the 3 types of treatment studied were included. A total of 8,087 studies were screened.; Data Collection: Data were synthesized using the statistical package Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). For dichotomous outcomes, the odds ratio (OR) and 95% confidence interval (CI) were derived for each study. Heterogeneity between the trial results was evaluated using the standard test, I 2 statistic.; Data Synthesis: When comparing misoprostol with medical vacuum aspiration (MVA), the rate of complete abortion was higher in the MVA group (OR = 0.16; 95%CI = 0.07-0.36). Hemorrhage or heavy bleeding was more common in the misoprostol group (OR = 3.00; 95%CI = 1.96-4.59), but pain after treatment was more common in patients treated with MVA (OR = 0.65; 95%CI = 0.52-0.80). No statistically significant differences were observed in the general acceptability of the treatments.; Conclusion: Misoprostol has been determined as a safe option with good acceptance by patients.; Competing Interests: The authors have no conflict of interests to declare. (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Silva-Bermudez Lina, S., et al. (2020). "Effects of oral contraceptives on metabolic parameters in adult premenopausal women: a meta-analysis." Endocrine connections 9(10): 978-998.
	Objective: To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis.; Patients and Methods: Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration (<12 months vs ≥12 months) and polycystic ovary syndrome (PCOS) status.; Results: Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (-7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration.; Conclusion: Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

Silver Madison, C., et al. (2021). "Frequency and impact of the inclusion of broader measures of value in economic evaluations of vaccines." Vaccine 39(46): 6727-6734.
	Background: The health and economic benefits of immunization may extend beyond the elements traditionally included in cost-effectiveness analyses (CEAs). This review investigated how broader impacts are considered in economic evaluations of vaccines and whether their inclusion would substantially change CEA findings.; Methods: We reviewed CEAs of vaccines associated with the largest global health burden, published from 2014 to 2019 using the Tufts CEA Registry and Tufts Global Health CEA Registry. We supplemented this with a systematic review of published and grey literature. We conducted descriptive analyses to examine the frequency of inclusion of specific social factors and study characteristics associated with their inclusion. We also conducted a case study of the human papilloma virus (HPV) vaccine to illustrate the potential change in CEA findings from selected social impacts.; Results: We identified 475 relevant health economic assessments. Overall, 40% of studies included at least one category of social impact. The most commonly included non-healthcare cost among cost-per-QALY studies was productivity (25%), while cost-per-DALY studies reported transportation costs most frequently (24%). Few studies examined the impact of vaccination on other sectors such as education and housing (<3%). Middle-income and North American settings were positively associated with social impact inclusion, while sub-Saharan African location was negatively associated. In the HPV case study, the addition of nonhealth costs improved cost-effectiveness by up to 90% or made the vaccine cost-saving, depending on geographic setting. The cost-saving scenario saved up to $30,000 in costs per case of cervical cancer averted.; Conclusions: A minority of vaccine CEAs include social impacts, particularly for nonhealth sectors. The omission of these impacts may result in a systematic undervaluation of vaccines from a societal perspective. Further efforts are required to document the full benefits of vaccination for policymaker consideration.; Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors report funding and employment from Merck & Co. CEVR is funded by multiple parties, including the PhRMA Foundation (through our Center for Enhanced Value Assessment), the Bill and Melinda Gates Foundation, Arnold Ventures, and other government, foundation, and pharmaceutical industry sources. CEVR also maintains the Cost-Effectiveness Analysis Registry (CEA) and Global Health CEA databases, which are supported by several dozen organizations, including drug industry and academic and nonprofit foundation sources. The authors report personal fees from several pharmaceutical and consulting companies, outside the submitted work. (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Simaei, S. R., et al. (2024). "Lavender and metformin effectively propagate progesterone levels in patients with polycystic ovary syndrome: A randomized, double-blind clinical trial." Fitoterapia 172: 105720.
	Background: The present study aimed to evaluate the impacts of lavender and metformin on polycystic ovary syndrome (PCOS) patients. Method(s): We performed a randomized, double-blind clinical trial including 68 females aged 18 to 45, fulfilling the Rotterdam criteria for PCOS. The patients were randomized to receive lavender (250 mg twice daily) or metformin (500 mg three times a day) for 90 days. The serum progesterone was measured at baseline and after 90 days, one week before their expected menstruation. Moreover, the length of the menstrual cycle was documented. Result(s): Our results showed that lavender and metformin treatment notably increased the progesterone levels in PCOS patients (increasing from 0.35 (0.66) and 0.8 (0.69) to 2.5 (6.2) and 2.74 (6.27) ng/mL, respectively, P < 0.001). However, we found no significant differences between the increasing effects of both treatments on progesterone levels. In addition, all patients in the lavender or metformin groups had baseline progesterone levels <3 ng/mL, reaching 14 (45.2%) patients >3 ng/mL. Lavender and metformin remarkably attenuated the menstrual cycle length in PCOS patients (decreasing from 56.0 (20.0) and 60 (12.0) to 42.0 (5.0) and 50.0 (14.0) days, respectively, P < 0.001). Furthermore, the decreasing effects of lavender on the menstrual cycle length were greater than the metformin group; however, it was not statistically significant (P = 0.06). Conclusion(s): Lavender effectively increased progesterone levels and regulated the menstrual cycles in PCOS patients, similar to metformin. Therefore, lavender may be a promising candidate for the treatment of PCOS.Copyright © 2023 Elsevier B.V.

Siminiuc, R. and D. Ţurcanu (2023). "Impact of nutritional diet therapy on premenstrual syndrome." Frontiers in Nutrition 10: 1079417.
	Premenstrual syndrome (PMS) is one of the most common disorders faced by women of reproductive age. More than 200 symptoms of varying severity associated with PMS have been identified. Because of the broad spectrum of action of PMS and its impact on quality of life, symptom relief is the main challenge of treating PMS and premenstrual dysphoric disorder (PMDD). The review aims to analyze and identify the potential impact of dietary and nutritional therapies on PMS and, respectively, for its better management. The study was conducted by accessing Internet databases such as PubMed, ScienceDirect, and Scopus and using relevant keywords such as PMS, symptoms, dietary patterns (DPs), macro and micronutrients, and supplements. The results showed that diet is an essential modulating factor in reducing and managing PMS symptoms. But research on the actual effect of foods and nutrients on PMS is sparse, sporadic, and studied with insufficient scientific rigor. No correlations were identified between the consumption of macronutrients and PMS: protein, fat, carbohydrates, and fiber, but the effectiveness of micronutrients, especially calcium, magnesium, vitamin D, B vitamins, and herbal supplements, was demonstrated. Researchers remain unanimous that the evidence is insufficient and limited to support their use as an effective treatment. Nevertheless, the results could contribute to providing quality information to help women and girls make evidence-based decisions regarding premenstrual health and the adoption of dietary and nutritional therapies.

Simon, J., et al. (2023). "Elagolix Plus Add-Back Consistently Improves Uterine Fibroids-Associated Bleeding and Nonbleeding Symptoms Across Subpopulations." Obstetrics and Gynecology 141(5 Supplement 1): 102S.
	INTRODUCTION: Patients with heavy menstrual bleeding (HMB) associated with uterine fibroids (UFs) have significantly improved menstrual blood loss (MBL) when taking elagolix+estradiol/norethin-drone acetate add-back therapy (ELA+AB) versus placebo. However, data on the effect of ELA+AB on nonbleeding symptoms are limited. METHOD(S): This post hoc analysis from the duplicate, IRB-approved, randomized, double-blind, placebo-controlled, 6-month, phase 3 Elaris UF-1 and UF-2 studies (NCT02654054 and NCT02691494) evaluated the Patients Global Impression of Change (PGIC). Patients rated symptom change for menstrual bleeding (MB) and nonbleeding symptoms on a 7-point scale from "very much improved" (1) to "very much worse" (7). RESULT(S): By 6 months, scores for the PGIC-MB and the domains of "abdominal or pelvic pain," "abdominal or pelvic pressure," "abdominal or pelvic cramping," "back pain," and "abdominal bloating" were significantly better (P,.001 for all; no adjustment for multiple comparisons were made) in the ELA+AB versus placebo groups, regardless of patient age (,40 years, 40 to,45 years, >45 years), baseline MBL (less than median [187.0 mL], greater than or equal to median), International Federation of Gynecology and Obstetrics (FIGO) classification (0-3, 4, 5-8), or baseline uterine volume (less than median [356.5 cm3], greater than or equal to median). Patients receiving ELA+AB reported PGIC domain scores that consistently exceeded "minimally improved" (<3) and often reached or exceeded "much improved" (<2) by 6 months. CONCLUSION(S): ELA+AB provides better bleeding and nonbleeding symptom improvement versus placebo for patients with HMB associated with UFs, regardless of subpopulation investigated. In all populations, PGIC-MB and domain scores consistently reached or exceeded "much improved" by 6 months with ELA+AB.

Simon, J., et al. (2023). "Elagolix with Add-Back Rapidly Improves Nonbleeding Symptoms in Individuals with Fibroid-Associated Heavy Menstrual Bleeding." Obstetrics and Gynecology 141(5 Supplement 1): 13S.
	INTRODUCTION: Elagolix+estradiol/norethindrone acetate add-back therapy (ELA+AB) significantly improves heavy menstrual bleeding (HMB) in patients with uterine fibroids (UFs). Data on the effect of ELA+AB on nonbleeding symptoms in HMB-UF patients are limited. METHOD(S): Elaris UF-1 and UF-2 (NCT02654054 and NCT02691494) were duplicate, IRB-approved, randomized, doubleblind, placebo-controlled, 6-month phase 3 studies. This post hoc analysis evaluated the Patients Global Impression of Change (PGIC) for menstrual bleeding (MB) and nonbleeding symptoms. Patients rated symptom change on a 7-point scale from "very much improved" (1) to "very much worse" (7). RESULT(S): Among responders (6-month MBL,80 mL and $50% MBL reduction from baseline), mean (SD) PGIC-MB and PGIC-abdominal bloating were better for ELA+AB versus placebo as early as 1 month (2.1 [1.3], n5199 versus 2.8 [1.5], n522; and 3.1 [1.2], n5201 versus 3.7 [1.0], n521, respectively) through 6 months (1.3 [0.9], n5221 versus 2.9 [1.3], n513; and 2.3 [1.3], n5221 versus 3.7 [0.9], n513, respectively). Patients treated with ELA+AB had improvement in symptoms at 3 months compared to placebo and at 6 months reached scores in the domains abdominal/pelvic pain (1.8 [1.1] versus 3.2 [1.0]), abdominal/pelvic pressure (1.9 [1.2] versus 3.4 [0.9]), abdominal/pelvic cramping (1.8 [1.0] versus 2.9 [1.2]), and back pain (2.3 [1.3] versus 3.2 [1.0]). Similar results were observed for the total patient population. CONCLUSION(S): ELA+AB provides rapid bleeding and nonbleeding symptom improvement for patients with UF-associated HMB. Improvement for ELA+AB-treated patients was observed as early as 1 month, with nonbleeding PGIC scores consistently approaching "much and very much improved" in all domains by 6 months.

Simon, J., et al. (2023). "Long-Term Safety of Elagolix with Add-Back in Women with Endometriosis-Associated Pain: 36-Month Results." Obstetrics and Gynecology 141(5): 13S.
	INTRODUCTION: Herein, we report updated safety results to 36 months from an ongoing phase 3, 48‐month study evaluating the longterm safety of elagolix (ELA) with add‐back (AB) for endometriosis‐associated pain (EAP) (NCT03213457). METHODS: Premenopausal women with moderate‐to‐severe EAP were randomized in this IRB‐approved study 4:1:2 to receive 12‐month blinded treatment with ELA 200 mg twice daily (BID)+AB, ELA 200 mg BID for 6 months followed by 6‐month ELA+AB, or placebo; followed by open‐label ELA+AB for all patients for 36 months. This 36‐month analysis assessed long‐term safety, including bone mineral density (BMD). RESULTS: Throughout the open‐label treatment period up to 36 months, BMD mean percent change from baseline measurements remained relatively stable at the total hip and lumbar spine and showed a decrease between 1% and 2% in the femoral neck over the open‐label period. At 36 months, mean percent change from baseline in BMD for patients treated with ELA+AB throughout the study was 20.77% (spine, n594); 20.36% (total hip, n592); and 21.39% (femoral neck, n592). The overall safety profile of ELA+AB, including AEs and SAEs, observed up to 36 months of treatment continues to be consistent with that previously observed at 12 and 24 months. CONCLUSION: This was the longest evaluation of ELA+AB to date. ELA+AB continued to maintain a favorable safety profile with minimal long‐term effect on BMD and no newly identified safety events to 36 months. Combined with previously reported efficacy data, these safety data suggest ELA+AB may provide a long‐term therapeutic option for women with EAP beyond 24 months.

Simon, J. A., et al. (2023). "LONG-TERM THERAPY OF ELAGOLIX + ADD-BACK THERAPY IN WOMEN WITH ENDOMETRIOSIS-ASSOCIATED PAIN FOR 48 MONTHS: a SAFETY UPDATE ON BONE MINERAL DENSITY DATA OF A PHASE 3 STUDY." Fertility and Sterility 120(4): e62.
	OBJECTIVE: To report the 48‐month bone mineral density data of a phase 3 study evaluating the long‐term safety of elagolix 200 mg twice daily (ELA) with add‐back therapy (AB, estradiol 1 mg/0.5 mg norethindrone acetate) for treatment of endometriosis‐associated pain (EAP; NCT03213457). MATERIALS AND METHODS: Premenopausal women with moderate to severe EAP were randomized 4:1:2 to 12‐month double‐blinded treatment with ELA+AB, ELA for 6 months followed by ELA+AB for 6 months, or placebo. Following blinded treatment, all patients received open‐label ELA+AB for an additional 36 months. Data in this report are presented for a 48‐month analysis of bone mineral density (BMD) in patients who received ELA+AB in both the double‐blind and open‐label treatment periods. RESULTS: Least squares mean percent change from baseline measurements of BMD in lumbar spine and total hip remained relatively stable during the open‐label treatment phase up to 48 months among patients who received ELA+AB throughout the study (Table). In the femoral neck, a small decrease in BMD (< 1% per year) was noted through month 30, which then remained stable through month 48. [Formula presented] CONCLUSIONS: This 48‐month study was the longest evaluation of ELA+AB to date in patients with EAP, and this analysis showed that ELA+AB had minimal long‐term impact on BMD in premenopausal women with moderate‐to‐severe EAP. IMPACT STATEMENT: Combined with previously reported efficacy data, these data support that ELA+AB may provide a long‐term, therapeutic option for moderate to severe EAP through 48 months. SUPPORT: AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of this abstract for submission. All authors had access to the relevant data and participated in the drafting, review, and approval of this abstract, and agreed in the decision to submit this abstract to ASRM23 for consideration as a poster or oral presentation. No honoraria or payments were made for authorship. Medical writing support was provided by Ray Beck, Jr, PhD, and Tracy Wetter, PhD, CMPP, of JB Ashtin, and funded by AbbVie.

Simon, P., et al. (2021). "Does colonoscopy have a role in the pre-operative investigation of bowel-involving deep infiltrating endometriosis? A systematic review."
	
Simon, S., et al. (2022). "A promising future for endometriosis diagnosis and therapy: Extracellular vesicles. A systematic review."
	
Simon, S., et al. (2021). "Prevention of posttraumatic stress disorder in mothers of preterm infants using trauma-focused group therapy: Manual development and evaluation." Early Human Development 154: 105282.
	Background: Preterm birth has been associated with a number of adverse maternal psychological outcomes. Aim(s): The current study aims to develop and evaluate the feasibility of a trauma-focused group intervention that is designed to reduce maternal symptoms of anxiety, depression, and posttraumatic stress in a sample of mothers of preterm infants hospitalized in a neonatal intensive care unit (NICU). Study design: The study was a one-group pre-/post quasi-experimental design. Participants received a 6-session intervention targeting parental trauma. Subjects: English-speaking mothers (N = 19) greater than 18 years of age of infants 23-34 weeks gestational age hospitalized in the NICU at Lucile Packard Children's Hospital Stanford. Outcome measures: Beck Anxiety Inventory (BAI), Beck Depression Inventory, Second Edition (BDI-II), Davidson Trauma Scale (DTS). Result(s): Results from the study indicate that the intervention is feasible, able to be implemented with a high degree of fidelity, is rated as highly satisfactory by participants, and leads to statistically significant reductions in symptoms of anxiety, depression, and posttraumatic stress at 6-week and 6-month follow-ups. Conclusion(s): Though encouraging, these findings are preliminary, and future studies should strive to reproduce these findings with a larger sample size and a comparison group.Copyright © 2020 Elsevier B.V.

Simopoulou, M., et al. (2019). "The Impact of Autoantibodies on IVF Treatment and Outcome: A Systematic Review." International Journal of Molecular Sciences 20(4).
	The role of autoantibodies in in vitro fertilization (IVF) has been discussed for almost three decades. Nonetheless, studies are still scarce and widely controversial. The aim of this study is to provide a comprehensive systematic review on the possible complications associated to autoantibodies (AA) impeding the chances of a successful IVF cycle. An Embase, PubMed/Medline and Cochrane Central Database search was performed on 1 December 2018, from 2006 until that date. From the 598 articles yielded in the search only 44 relevant articles ultimately fulfilled the inclusion criteria and were qualitatively analyzed. Five subsets of results were identified, namely, thyroid related AA, anti-phospholipid antibodies, anti-nuclear antibodies, AA affecting the reproductive system and AA related to celiac disease. It may be implied that the majority of auto-antibodies exert a statistically significant effect on miscarriage rates, whereas the effects on clinical pregnancy and live birth rates differ according to the type of auto-antibodies. While significant research is performed in the field, the quality of evidence provided is still low. The conduction of well-designed prospective cohort studies is an absolute necessity in order to define the impact of the different types of autoantibodies on IVF outcome.

Simpson, G., et al. (2022). "What's out There? A Systematic Review of the Efficacy and Availability of Targeted Treatments for Central Sensitisation in Women with Endometriosis." The Clinical Journal of Pain.
	OBJECTIVES: Central sensitisation contributes to patient variability when treating pain in endometriosis. Targeting this process may alleviate hyperalgesia and allodynia in women refractory to current treatments. Thus far, there has been no review of targeted treatments for central sensitisation in women with endometriosis. Therefore, this review aims to identify and summarise the findings of studies regarding the availability and efficacy of targeted treatments for central sensitisation in women with endometriosis. METHODS: A systematic review was conducted searching MEDLINE, Embase and CINAHL. Inclusion criteria: primary research articles, women with endometriosis and central sensitisation features, and description of treatments for central sensitisation, or its effects on hyperalgesia and allodynia. Exclusion criteria: review articles, letters to the editor, commentaries, editorials, protocols, or women with endometriosis infiltrating nerves. Risk of bias analysis was conducted. Data was reviewed and summarised by treatment method. RESULTS: Eight studies met inclusion criteria, demonstrating limited research in this area. Four treatment options were addressed: surgical approaches, nerve stimulation approaches, injection-based therapies, and hormonal therapies. Surgery and nerve stimulation appear the most promising treatments for central sensitisation. Injections have limited and mixed evidence of efficacy. Limited evidence suggests hormonal therapies may be ineffective. DISCUSSION: Given the lack of evidence for any treatment, all require further research to determine treatment efficacy before options will be available clinically. There is a clear need for consistency in defining and identifying central sensitisation in study populations. This review identifies areas of interest, particularly surgery and nerve stimulation, from which future research must stem.

Simrit, N., et al. (2024). "A systematic review of treatment outcomes for Caesarean scar ectopic pregnancy research."
	
Sinai Icahn School of Medicine at, M. (2023). Sacituzumab Govitecan in Combination With Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer.
	No Results Available Drug: Sacituzumab|Drug: Cisplatin Dose-limiting toxicity (DLT) for the Safety Run-In Phase|Dose limiting toxicity (DLT) for the DEC Phase|Overall Response Rate (ORR)|Clinical Benefit Response (CBR)|Progression free survival (PFS) Female Phase 1|Phase 2 54 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment STUDY-22-00832 September 7, 2026

Singh, A., et al. (2023). "Efficacy of a Proprietary Fenugreek Seed Extract (Trigonella foenum-graecum, Furocyst) in Women with Polycystic Ovary Syndrome (PCOS): a Randomized, Double-Blind, Placebo-Controlled Study." Journal of the American Nutrition Association 42(7): 651-659.
	Introduction: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia, a quite common heterogenous endocrine/hormonal disorder, and accompanied by elevated androgen level, menstrual irregularity, and hirsutism. The consequences include infertility or miscarriage. It is a challenging problem to the physicians. In a one-arm, non-randomized preliminary investigation in fifty premenopausal women, we demonstrated the efficacy of Furocyst, a patented, standardized Trigonella foenum-graecum extract, in ameliorating the symptoms of PCOS over a period of 90 consecutive days. Objective(s): In the present study, a double-blind, two-arm, single-center, randomized, comparative study was conducted to assess the efficacy of Furocyst (2 capsules of 500 mg/day) in 208 pre-menopausal women diagnosed with PCOS. Method(s): Ethical committee approval was obtained. A total of 208 subjects (placebo = 95; Furocyst = 113; age:18-45 years, BMI < 42 kg/m2) completed the investigation. The comparative efficacy of placebo and Furocyst was assessed on the number of cysts, ovarian volume, hirsutism, LH:FSH ratio, titer of TSH, SHBG, prolactin and free testosterone. Key clinical parameters such as fasting blood glucose levels, HOMA Index, cholesterol, LDL, and triglyceride levels, as well as total blood chemistry were also investigated Results: Furocyst supplementation significantly reduced the number of cysts, ovarian volume, and hirsutism levels, as well as normalized the menstrual cycle in Furocyst-treated subjects as compared to placebo group. Furocyst significantly reduced luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and thyroid stimulating hormone (TSH) levels, and reduced the prolactin and SHBG levels. Furocyst significantly reduced the fasting blood glucose levels, HOMA Index, cholesterol, LDL, and triglyceride levels as compared to the placebo group, while the free testosterone levels were significantly decreased in the Furocyst group. Conclusion(s): The studies collectively demonstrated the efficacy of Furocyst as a safe, natural phytochemical-based formulation to alleviate the symptoms of PCOS. No significant adverse events were observed.Copyright © 2022 American Nutrition Association.

Singh, B., et al. (2021). "A Phase I Clinical Trial to Assess Safety and Tolerability of Injectable Collagenase in Women with Symptomatic Uterine Fibroids." Reproductive sciences (Thousand Oaks, Calif.) 28(9): 2699‐2709.
	Uterine fibroids feature excessive deposition of types I and III collagen. Previous ex vivo studies showed an FDA‐approved collagenase (EN3835)‐digested types I and III collagen fibers in fibroid tissues; however, collagenase had not been evaluated in vivo for effects on uterine fibroids. The objective was to assess the safety and tolerability of collagenase injection directly into uterine fibroids. This was a prospective, open label, dose escalation study. The study participants were fifteen women aged 35–50 years with symptomatic uterine fibroids planning to undergo hysterectomy. Three subjects received saline and methylene blue, three subjects received a fixed dose of EN3835, and 9 subjects received stepped, increasing dosages of EN3835, all by transvaginal, ultrasound‐guided injections. Primary outcome measures were safety and tolerability of the injection and change in collagen content between treated and control tissues. There were no significant adverse events following injection of EN3835 into uterine fibroids. Masson’s trichrome stains revealed a 39% reduction in collagen content in treated samples compared to controls (p <0.05). Second harmonic generation (SHG) analysis showed treated samples to have a 21% reduction in density of collagen compared to controls. Picrosirius‐stained collagenase‐treated fibroids showed collagen fibers to be shorter and less dense compared to controls. Subjects reported a decrease in fibroid‐related pain on the McGill Pain Questionnaire after study drug injection in Group 2 at both 4–8 days and 60–90 days post‐injection. The findings indicated that injection of collagenase was safe and well tolerated. These results support further clinical investigation of collagenase as a minimally invasive treatment of uterine fibroids. NCT0289848.

Singh, S. (2022). "Few concerns about evidence - feasibility and safety of performing cesarean myomectomy: a systematic review and meta-analysis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 35(25): 7513.
	
Singh, S., et al. (2023). "Contemporary approaches in the management of uterine leiomyomas." European Journal of Obstetrics, Gynecology, and Reproductive Biology 287: 195-210.
	Background: Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention.; Objective: Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas.; Search Strategy: PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA).; Results: Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas.; Conclusion: Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Singh Sukhbir, S., et al. (2020). "Surgical Outcomes in Patients With Endometriosis: A Systematic Review." Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 42(7): 881.
	Objective: Among women treated surgically for endometriosis-associated pain, comprehensive data are lacking on the proportions of patients who experience little or no symptom relief, develop recurrent symptoms, or require further surgical treatment for endometriosis. The aim of this study was to assess the efficacy of surgical procedures used to treat endometriosis-associated pain.; Methods: Medline and Embase were searched on October 13, 2016. Articles referring to women undergoing surgery for the treatment of endometriosis-associated pain were screened by two independent investigators. For each included treatment arm, data were extracted for the proportion of patients reporting partial or no improvement after surgery for endometriosis-associated pain, pain recurrence, or requirement for further surgery.; Results: A total of 38 studies were included. Most studies did not report relevant outcomes to evaluate pain (71.1%) and recurrent surgery (68.4%). Of the women who underwent lesion excision, 11.8% reported no improvement in pain, and 22.6% underwent further surgery. Postoperative pain, recurrent pain, and adverse events were reported by 34.3%, 28.7%, and 14.8%, respectively, of patients who underwent excision or ablation of endometriosis combined with pelvic denervation and in 25.0%, 15.8%, and 8.1% of women who underwent lesion excision alone. Of the patients who were treated surgically for deep endometriosis affecting the bowel and/or bladder, 7.0% experienced recurrent symptoms, and 4.1% underwent further surgery.; Conclusion: This review supports the findings of previous studies and highlights the need for standardized reporting and more detailed follow-up after surgery for endometriosis-associated pain. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Singla, D. R., et al. (2021). "Implementation and Effectiveness of Nonspecialist-Delivered Interventions for Perinatal Mental Health in High-Income Countries: A Systematic Review and Meta-analysis." JAMA Psychiatry 78(5): 498-509.
	Importance: Task sharing - or training of nonspecialist providers with no formal training in counseling - is an effective strategy to improve access to evidence-based counseling interventions and has the potential to address the burden of perinatal depression and anxiety. Objective(s): To identify the relevant implementation processes (who, what, where, and how) and to assess the effectiveness of counseling interventions delivered by nonspecialist providers for perinatal depression and anxiety in high-income countries. Data Sources: CINAHL, Ovid MEDLINE, Ovid MEDLINE In-Process, PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and Embase through December 31, 2019. Relevant systematic reviews were also considered. Study Selection: Randomized clinical trials of counseling interventions that assessed depression or anxiety after intervention, delivered by a nonspecialist provider for adults, and that targeted perinatal populations in a high-income country were included. Self-help interventions that did not include a provider component were excluded. Data Extraction and Synthesis: Four researchers independently reviewed abstracts and full-text articles, and 2 independently rated the quality of included studies. Random-effects meta-analysis was used to estimate the benefits of the interventions. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Main Outcomes and Measures: For implementation processes, the frequencies represented by a total or percentage were estimated, where the denominator is the total number of eligible trials, unless otherwise indicated. For effectiveness, primary and secondary outcome data of depression, anxiety, or both symptoms were used, with separate analyses for prevention and treatment, stratified by depression or anxiety. Subgroup analyses compared outcome types (anxiety vs depression) and study objectives (treatment vs prevention). Result(s): In total, 46 trials (18321 participants) were included in the systematic review; 44 trials (18101 participants) were included in the meta-analysis. Interventions were implemented across 11 countries, with the majority in Australia, UK, and US. Two-thirds (65%) of counseling interventions were provided by nurses and midwives, lasted a mean of 11.2 weeks (95% CI, 6.4-16.0 weeks), and most were delivered face to face (31 [67.4%]). Only 2 interventions were delivered online. A dearth of information related to important implementation processes, such as supervision, fidelity, and participant sociodemographic characteristics, was observed in many articles. Compared with controls, counseling interventions were associated with lower depressive symptoms (standardized mean difference [SMD], 0.24 [95% CI, 0.14-0.34]; 43 trials; I2= 81%) and anxiety scores (SMD, 0.30 [95% CI, 0.11-0.50]; 11 trials; I2= 80%). Treatment interventions were reported to be effective for both depressive symptoms (SMD, 0.38 [95% CI, 0.17-0.59]; 15 trials; I2= 69%) and anxiety symptoms (SMD, 0.34 [95% CI, 0.09-0.58]; 6 trials; I2= 71%). However, heterogeneity was high among the trials included in this analysis. Conclusions and Relevance: This study found evidence in high-income countries indicating that nonspecialist providers may be effective in delivering counseling interventions. Additional studies are needed to assess digital interventions and ensure the reporting of implementation processes to inform the optimal delivery and scale-up of these services..Copyright © 2021 American Medical Association. All rights reserved.

Singla, D. R., et al. (2021). "Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial." Trials 22(1): 186.
	Background: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven.; Methods: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms.; Discussion: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety.; Trial Registration: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Sinha, B. and S. Ghosal (2021). "A meta-analysis of the effect of sodium glucose cotransporter-2 inhibitors (SGLT-2is) on metabolic parameters in patients with polycystic ovary syndrome (PCOS)." ResearchSquare.
	Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of childbearing age and is associated with multiple morbidities. However, treatment for this condition is mainly applied for symptomatic relief and does not address the complex pathophysiology of this condition. This meta-analysis was conducted on the usage of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in PCOS because this group of drugs presents an attractive strategy to address the metabolic and hormonal defects by managing the pathophysiological defects observed in this syndrome. Methods We included prospective trials that enrolled patients with established PCOS and compared an SGLT-2i group versus a control group with at least 2 weeks of follow-up. The standardized mean difference (SMD) was used for effect size estimation from individual studies and was pooled using the fixed effect model. Results We included four trials with a pooled population of 158 patients with documented PCOS who received either an SGLT-2i or standard management. From a metabolic perspective, significant improvements were observed in the reduction in body weight (SMD: -0.68, 95% CI -1.16 to -0.19, < 0.01), fasting plasma glucose (FPG) (SMD: -0.59, 95% CI -0.99 to -0.19, P < 0.01), and insulin resistance as assessed with the HOMA-IR (SMD: -0.39, 95% CI -0.76 to -0.03, P = 0.03). In addition, a significant improvement was noted in dehydroepiandrosterone sulphate (DHEAS) levels (SMD: -0.55, 95% CI -0.94 to -0.16, P < 0.01). Conclusion SGLT-2i use is associated with salutary outcomes of metabolic and anthropometric markers of PCOS and likely favourable hormonal effects.

Sinha, B. and S. Ghosal (2022). "A Meta-Analysis of the Effect of Sodium Glucose Cotransporter-2 Inhibitors on Metabolic Parameters in Patients With Polycystic Ovary Syndrome." Frontiers in Endocrinology 13: 830401.
	Objective: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of childbearing age and is associated with multiple morbidities. However, treatment for this condition is mainly applied for symptomatic relief and does not address the complex pathophysiology of this condition. This meta-analysis was conducted on the usage of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in PCOS because this group of drugs presents an attractive strategy to address the metabolic and hormonal defects by managing the pathophysiological defects observed in this syndrome.; Methods: We included prospective trials that enrolled patients with established PCOS and compared an SGLT-2i group versus a control group with at least 2 weeks of follow-up. The standardized mean difference (SMD) was used for effect size estimation from individual studies and was pooled using the fixed effect model.; Results: We included four trials with a pooled population of 158 patients with documented PCOS who received either an SGLT-2i or standard management. From a metabolic perspective, significant improvements were observed in the reduction in body weight (SMD: -0.68, 95% CI -1.16 to -0.19, <0.01), fasting plasma glucose (FPG) (SMD: -0.59, 95% CI -0.99 to -0.19, P<0.01), and insulin resistance as assessed with the HOMA-IR (SMD: -0.39, 95% CI -0.76 to -0.03, P=0.03). In addition, a significant improvement was noted in dehydroepiandrosterone sulphate (DHEAS) levels (SMD: -0.55, 95% CI -0.94 to -0.16, P<0.01).; Conclusion: SGLT-2i use is associated with salutary outcomes of metabolic and anthropometric markers of PCOS and likely favourable hormonal effects.; Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021268564], PROSPERO 2021 CRD42021268564.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Sinha and Ghosal.)

Sini, L., et al. (2023). "Effectiveness of non-pharmacological interventions for improving the mental health and other psychosocial outcomes of parents with pregnancy loss: A systematic review and meta-analysis."
	
Siobhan, S., et al. (2021). "Urologic chronic pelvic pain syndrome flares: a systematic review of their terminology, manifestation, triggers, and therapies."
	
Siristatidis, C., et al. (2022). "A Randomized Controlled Trial on the Efficacy and Safety of Low-Dose hCG in a Short Protocol with GnRH Agonist and Ovarian Stimulation with Recombinant FSH (rFSH) During the Follicular Phase in Infertile Women Undergoing ART." Reproductive sciences (Thousand Oaks, Calif.) 29(2): 497-505.
	Τhis study aims to investigate whether the addition of low-dose hCG throughout stimulation in infertile women undergoing IVF improves IVF outcome parameters. This is a prospective, multicenter, randomized, double-blind, placebo-controlled, Phase IIIb clinical study, conducted in three university IVF units. We studied whether the addition of 100 IU hCG/day to a short GnRH agonist IVF protocol from the onset of the follicular phase (group 1, n=40) or placebo (group 2, n=41) had any impact on the number of high-quality transferred embryos at day 2 and clinical pregnancy rates. The comparison encompassed descriptive statistics, and univariate and multivariate analyses. Concerning the primary outcomes, we found no differences in both the number of high-quality embryos (≥2) at day 3 [21/40 (52.5%) vs. 14/41 (34.2%), p=0.095] and clinical pregnancy rates [10/40 (25%) vs. 10/41 (24.4%), p=0.949], respectively. Similarly, there were no differences concerning the secondary outcomes preset for this trial. According to the results of the multivariate logistic regression analysis, no significant associations were noted for primary outcomes (clinical pregnancy: adjusted OR=0.89, 95% CI: 0.29-2.75; (≥2 excellent quality embryos at day 3: adjusted OR=0.54, 95% CI: 0.21-1.42, with group 1 set as reference category); similarly, no differences were noted with respect to secondary outcomes, except from the increased odds of ≥2 poor-quality embryos at day 3 occurring in group 2 (adjusted OR= 11.69, 95%CI: 1.29-106.19). The addition of low-dose hCG to a short GnRH agonist protocol for IVF does not improve the number of top-quality embryos and clinical pregnancy rates. (© 2021. Society for Reproductive Investigation.)

Skorstengaard, M., et al. (2019). "Condom use to enhance regression of cervical intraepithelial neoplasia: study protocol for a randomized controlled trial." Trials 20(1): 473.
	Background: Condom use can reduce the risk of infection by human papillomavirus (HPV). Furthermore, it has been suggested that condom use can increase the regression rate of cervical lesions. In Denmark, women with cervical intraepithelial neoplasia grade 2 (CIN2) and a future wish to conceive are not treated immediately but are followed up by a gynecologist about 6 months later. The aim of this project was to determine if advising women to have their male partners to use a condom during sexual intercourse in the follow-up period can increase the regression rate of CIN2.; Methods/design: This is a randomized clinical trial of women with CIN2. The intervention group was advised to use condoms between the date of diagnosis and the date of their follow-up visit. The control group received standard care. Cervical samples were tested for HPV. The primary endpoint will be the intention-to-treat analysis with the relative rate of CIN2 regression between the intervention group and the control group. Regression is defined as <CIN2 at the follow-up visit. In addition, a per-protocol analysis of the regression rate in women adhering to condom use compared with the control group will be performed. The secondary endpoint will be the HPV-clearance rate in the condom group.; Discussion: If condom use for 6 months can enhance the regression of cervical lesions, then more women can be spared conization. This is an efficient treatment of cervical lesions but is associated with an increased risk of preterm delivery.; Trial Registration: ClinicalTrials.gov, NCT02907333 . Registered on 14 September 2016.

Skoura, A., et al. (2024). "Diastasis Recti Abdominis Rehabilitation in the Postpartum Period: A Scoping Review of Current Clinical Practice." International Urogynecology Journal.
	INTRODUCTION AND HYPOTHESIS: Despite exercise being the standard approach to diastasis recti abdominis (DRA) rehabilitation, there is no consensus on the most effective exercise routine and adjunct modalities for reducing DRA and improving functional parameters. The present study is aimed at investigating evidence for DRA rehabilitation in postpartum women, as well as knowledge gaps and areas for future research. METHODS: For this scoping review a systematic search was conducted in MEDLINE, AMED, CINAHL, Embase, ScienceDirect, Scopus, and PEDro up to November 2022. Selection criteria included studies investigating exercise therapy interventions both with and without adjunct modalities for postpartum DRA. Sample characteristics, diagnostic criteria, program design, and outcome measures were recorded. Critical appraisal of clinical trials was performed using PEDro classification. RESULTS: Twenty-eight studies were included: 14 clinical trials, 3 case series, and 11 observational studies. DRA exercises that focused on deep and superficial muscles, pelvic floor muscles, respiratory maneuvers, functional exercises, or alternative interventions (yoga, suspension training, hypopressive exercise) and adjunct modalities showed promising results in reducing the inter-recti distance and related dysfunction. However, there was great variability in diagnostic criteria and methods, DRA severity, time post-birth, and exercise program design. CONCLUSIONS: Reviewed studies provide valuable insights into exercise therapy, but it is important to recognize their limitations, as variability in diagnostic criteria, sample characteristics, and exercise program design hinder the generalizability of the findings. Further high-quality research is needed to strengthen the evidence in this area and provide reliable recommendations for clinical practice.

Skowyra, A., et al. (2023). "The impact of splenectomy and diaphragmatic surgery on perioperative morbidity and overall survival of ovarian cancer patients." Ginekologia polska.
	OBJECTIVES: The prognosis of ovarian cancer (OC), among other factors, depends on residual disease after primary debulking surgery (PDS) and initial disease advancement. The main aim of our study was to evaluate the survival benefits of splenectomy and diaphragmatic surgery in OC patients, when the procedures result in resection to no macroscopic residual disease or minimal residual disease [tumor nodules below 2.5 mm according to Sugarbaker's completeness of cytoreduction score (CC) = 1]. MATERIAL AND METHODS: The study included 25 OC patients after splenectomy procedures, 28 patients after diaphragmatic surgery and 17 patients who had undergone both splenectomy and diaphragmatic surgery. Patients' overall survival (OS) was compared with residual disease-matched controls (47 patients) who had upper abdomen involvement but no requirement for splenectomy and/or diaphragmatic surgery. RESULTS: Overall survival of patients after splenectomy was not significantly different from OS of patients who did not required splenectomy (36.1 vs 31.6 months; p = 0.85). No differences in OS were observed between patients who did and did not require diaphragmatic surgery (31.3 vs 41.8; p = 0.33). Similarly, we found no differences in OS between patients who underwent both splenectomy and diaphragmatic surgery and those patients who did not require either procedure (20.1 vs 31.6 months; p = 0.45). Splenectomies and diaphragmatic surgeries were associated with prolonged hospitalization and length of surgery, however, no specific morbidity related to the procedures was observed. CONCLUSIONS: In the cases of advanced OC, diaphragm and spleen involvement do not hamper patient prognosis when adequately resected.

Slade, E., et al. (2020). "Primary surgical management of anterior pelvic organ prolapse: a systematic review, network meta-analysis and cost-effectiveness analysis." BJOG : an international journal of obstetrics and gynaecology 127(1): 18-26.
	Background: Anterior compartment prolapse is the most common pelvic organ prolapse (POP) with a range of surgical treatment options available.; Objectives: To compare the clinical effectiveness and cost-effectiveness of surgical treatments for the repair of anterior POP.; Methods: We conducted a systematic review of randomised controlled trials comparing surgical treatments for women with POP. Network meta-analysis was possible for anterior POP, same-site recurrence outcome. A Markov model was used to compare the cost-utility of surgical treatments for the primary repair of anterior POP from a UK National Health Service perspective.; Main Results: We identified 27 eligible trials for the network meta-analysis involving eight surgical treatments tested on 3194 women. Synthetic mesh was the most effective in preventing recurrence at the same site. There was no evidence to suggest a difference between synthetic non-absorbable mesh, synthetic partially absorbable mesh, and biological mesh. The cost-utility analysis, which incorporated effectiveness, complications and cost data, found non-mesh repair to have the highest probability of being cost-effective. The conclusions were robust to model inputs including effectiveness, costs and utility values.; Conclusions: Anterior colporrhaphy augmented with mesh appeared to be cost-ineffective in women requiring primary repair of anterior POP. There is a need for further research on long-term effectiveness and the safety of mesh products to establish their relative cost-effectiveness with a greater certainty.; Tweetable Abstract: New study finds mesh cost-ineffective in women with anterior pelvic organ prolapse. (© 2019 Royal College of Obstetricians and Gynaecologists.)

Sliwa, J., et al. (2021). "Anterior abdominal fixation - a new option in the surgical treatment of pelvic organ prolapse." Ginekologia polska 92(7): 471-474.
	OBJECTIVES: To present anterior abdominal fixation - a new surgical technique for the treatment of pelvic organ prolaps (POP) and to evaluate the results of the treatment of patients with stage III and IV POP operated using this technique. MATERIAL AND METHODS: Anterior abdominal fixation for treating stage III and IV POP was carried out in 42 women, who were qualified according to the Pelvic Organ Prolapse Quantification System (POP-Q) scale at baseline and after 12 months. The Pelvic Floor Disability Index-20 (PFDI-20), along with its symptom scales, were evaluated. RESULTS: The mean age 42 operated women was 64.5 years, and the average BMI was 27.3 (83% women were overweight). At baseline, 29 (69%) women had POP stage IV, and 13 (31%) women had POP stage III. Overall, 14 (33%) underwent laparoscopy, 28 (67%) underwent laparotomy. At 12 months, 14 (33.3%) women had POP stage I; 21 (50%) women had POP stage II. Seven patients (16.6%) experienced a recurrence of disease with advancement at the degree of III/IV; 4 (9.5%) women required adjuvant surgery in the form of anterior and posterior vaginal wall surgery. No early complications after surgery were observed. The comparison of the results before and after surgery showed statistically significant improvement in terms of the P-QoL score as well as PFDI-20 along with its 3 symptom scales. CONCLUSIONS: Anterior abdominal fixation of the uterus to the anterior abdominal wall is effective, safe, and technically easy to perform in the treatment of POP of advanced stage.

Slomovitz, B., et al. (2022). "KEYNOTE-C93/GOG-3064/ENGOT-EN15: PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF FIRST-LINE PEMBROLIZUMAB VERSUS PLATINUM-DOUBLET CHEMOTHERAPY IN MISMATCH REPAIR DEFICIENT ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA." International Journal of Gynecological Cancer 32(Supplement 3): A230.
	Objectives KEYNOTE-C93/GOG-3064/ENGOT-en15 (NCT05173987) is a phase 3, randomized, open-label study evaluating first-line pembrolizumab versus carboplatin-paclitaxel chemotherapy in patients with dMMR advanced or recurrent endometrial cancer (EC). Methods Patients aged >=18 years with histologically confirmed stage III/IV recurrent EC including carcinosarcoma (mixed Mullerian tumor), radiographically evaluable disease (measurable or nonmeasurable per RECISTv1.1), no prior systemic therapy (prior radiation with or without radiosensitizing chemotherapy >2 weeks before first dose or prior hormonal therapy >=1 week before randomization is permitted), and ECOG PS <=1 are eligible. Patients must have central confirmation of dMMR status. ~350 patients will be randomized 1:1 to pembrolizumab 400 mg IV Q6W for 18 cycles (~2 years) or carboplatin AUC 5 or 6 mg/mL/min IV Q3W and paclitaxel 175 mg/m2 IV Q3W for 6 cycles (with option for >6 cycles). Trastuzumab is permitted for patients in the chemotherapy arm with HER2+ serous EC. Randomization is stratified by disease status (newly-diagnosed advanced EC vs recurrent EC) and histology (endometrioid vs nonendometrioid). Treatment will continue for the specified number of cycles or until PD or unacceptable toxicity. Patients in the chemotherapy arm can receive pembrolizumab following confirmed PD by BICR. Dual primary endpoints are PFS per RECISTv1.1 by BICR and OS. Secondary endpoints are ORR, DCR, and DOR per RECISTv1.1 by BICR; PFS per RECISTv1.1 by investigator review; PFS2; safety; and PROs. Enrollment is ongoing. Results Trial in progress: there are no available results at the time of submission. Conclusions Trial in progress: there are no available conclusions at the time of submission.

Slomovitz, B., et al. (2022). "ENGOT-en11/GOG-3053/KEYNOTE-B21: A phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed high-risk endometrial cancer (570)." Gynecologic Oncology 166(Supplement 1): S278.
	Objectives: Pembrolizumab, a selective humanized anti-PD-1 monoclonal antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% objective response rate [ORR] as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer. ENGOT-en11/GOG-3O53/KEYNOTE-B21 (NCT04634877) is a phase III, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with endometrial cancer. Method(s): Eligible patients are >=18 years old with newly diagnosed, histologically confirmed high-risk (stage I/II non-endometrioid or with p53 abnormality and any histology, stage III/IVA), previously untreated endometrial cancer following surgery with curative intent with no evidence of disease postoperatively or on imaging. Approximately 990 patients are randomized to receive pembrolizumab 200 mg or placebo every three weeks (Q3W) for six cycles plus chemotherapy (carboplatin AUC of 5 or 6 plus paclitaxel 175 mg/m2 Q3W or carboplatin AUC of 2 or 2.7 plus paclitaxel 60 mg/m2 QW) in stage I. Patients receive pembrolizumab 400 mg or placebo Q6W for six cycles in stage II per their treatment assignment. At the investigator's discretion, radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) +/- radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and International Federation of Gynecology and Obstetrics (FIGO) surgical stage (I/II vs III/IVA). Dual primary endpoints are disease- free survival (DFS; per investigator assessment) and overall survival (OS), both estimated by the Kaplan-Meier method, with a stratified log-rank test to assess treatment differences and a Cox proportional hazard model with Efron's method of tie handling to assess the magnitude of treatment differences. Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0), and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and Endometrial Cancer Module [EORTC QLQ-EN24]). Enrolment began December 2020 and is ongoing; a total of 221 sites in 28 countries are planned.Copyright © 2022 Elsevier Inc.

Slomovitz, B. M., et al. (2022). "KEYNOTE-C93/GOG-3064/ENGOT-en15: A phase 3, randomized, open-label study of first-line pembrolizumab versus platinum-doublet chemotherapy in mismatch repair deficient advanced or recurrent endometrial carcinoma." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Carboplatin-paclitaxel chemotherapy (with trastuzumab for HER2+ uterine serous carcinoma) is the standard of care first-line systemic treatment for recurrent or metastatic endometrial carcinoma (EC), which has a 5-year relative survival rate of only 17%. Worse survival outcomes have been shown for the mismatch repair deficient (dMMR) subtype of EC. Pembrolizumab (pembro), an anti-PD-1 antibody, showed compelling antitumor activity in previously treated, advanced MSI-H/dMMR EC in the phase 2 KEYNOTE-158 study (ORR, 48%; median duration of response [DOR], not reached; O'Malley JCO 2022). KEYNOTE-C93/GOG-3064/ENGOT-en15 (NCT05173987) is a phase 3, randomized, open-label study evaluating first-line pembro versus carboplatin-paclitaxel chemotherapy in patients with dMMR advanced or recurrent EC. Method(s): Patients aged >=18 years with histologically confirmed stage III/IV recurrent EC including carcinosarcoma (mixed Mullerian tumor), radiographically evaluable disease (measurable or nonmeasurable per RECIST v1.1), no prior systemic therapy (prior radiation with or without radiosensitizing chemotherapy > 2 weeks before first dose or prior hormonal therapy >=1 week before randomization is permitted), and an ECOG PS <=1 are eligible. Patients must have central confirmation of dMMR status. Approximately 350 patients will be randomized 1:1 to receive pembro 400 mg IV Q6W for 18 cycles (~2 years) or carboplatin AUC 5 or 6 mg/mL/min IV Q3W and paclitaxel 175 mg/m2 IV Q3W for 6 cycles (with option for > 6 cycles). Trastuzumab is permitted for patients in the chemotherapy arm with HER2+ serous EC. Randomization is stratified by disease status (newly diagnosed advanced EC vs recurrent EC) and histology (endometrioid vs nonendometrioid). Treatment will continue for the specified number of cycles or until PD or unacceptable toxicity. Patients in the chemotherapy arm have the option to receive pembro following confirmed PD by blinded independent central review (BICR). Tumor imaging will be performed Q9W from randomization to week 54 and Q12W thereafter. AEs will be assessed from randomization to 30 days (90 days for serious AEs) after treatment discontinuation and graded per NCI CTCAE version 5.0. Dual primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints are ORR, disease control rate, and DOR per RECIST v1.1 by BICR; PFS per RECIST v1.1 by investigator review; PFS2 (ie, time from randomization to PD per investigator assessment or death from any cause after start of subsequent anticancer therapy); safety; and patient-reported outcomes. PFS and OS will be estimated by the Kaplan-Meier method, with treatment differences assessed by the stratified log-rank test and HRs with 95% CIs determined using a Cox proportional hazard model. Enrollment is ongoing.

Slomovitz Brian, M., et al. (2022). "A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study." Gynecologic Oncology 164(3): 481-491.
	Background: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC).; Objective: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC.; Study Design: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate.; Results: Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%]).; Conclusions: EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Slopnick Emily, A., et al. (2023). "Pudendal Nerve Block Analgesia at the Time of Vaginal Surgery: A Randomized, Double-Blinded, Sham-Controlled Trial." Urogynecology (Philadelphia, Pa.) 29(10): 827-835.
	Importance: Effective opioid-sparing postoperative analgesia requires a multimodal approach. Regional nerve blocks augment pain control in many surgical fields and may be applied to pelvic floor reconstruction.; Objective: This study aimed to evaluate the impact of pudendal nerve block on postoperative pain control and opioid consumption after vaginal surgery.; Study Design: In this randomized, double-blind, sham-controlled trial, we enrolled women undergoing pelvic reconstruction, excluding patients with chronic pelvic pain or contraindications to nonnarcotic analgesia. Patients were randomized to transvaginal pudendal nerve block (9 mL 0.25% bupivacaine and 1 mL 40 mg/mL triamcinolone) or sham injection (10 mL normal saline). Primary outcomes were pain scores and opioid requirements. Sixty patients were required to show a 20-mm difference on a 100-mm visual analog scale (VAS).; Results: We randomized 71 patients: 36 pudendal block and 35 sham. Groups were well matched in baseline characteristics and surgery type. Prolapse repairs were most common (n = 63 [87.5%]), and there was no difference in anesthetic dose or operative time. Pain scores were equivalent in the postanesthesia care unit (mean VAS, 53.1 [block] vs 56.4 [sham]; P = 0.517) and on postoperative day 4 (mean VAS, 26.7 [block] vs 35.5 [sham]; P = 0.131). On postoperative day 1, the intervention group reported less pain, but this did not meet our 20 mm goal for clinical significance (mean VAS, 29.2 vs 42.5; P = 0.047). A pudendal block was associated with lower opioid consumption at all time points, but this was not statistically significant.; Conclusions: Surgeon-administered pudendal nerve block at the time of vaginal surgery may not significantly improve postoperative pain control or decrease opioid use.; Competing Interests: The authors have declared they have no conflicts of interest. (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Smith Anna Jo, B., et al. (2021). "Minimally Invasive Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 28(3): 544.
	Objective: To compare recurrence rate, progression-free survival (PFS), and overall survival for early-stage cervical cancer after minimally invasive (MIS) vs abdominal radical hysterectomy.; Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Library databases.; Methods of Study Selection: We identified studies from 1990 to 2020 that included women with stage I or higher cervical cancer treated with primary radical hysterectomy and compared recurrence and/or PFS and overall survival with MIS vs abdominal radical hysterectomy. (The review protocol was registered with the International Prospective Register of Systematic Reviews: CRD4202173600).; Tabulation, Integration, and Results: We performed random-effects meta-analyses overall and by length of follow-up. Fifty articles on 40 cohort studies and 1 randomized controlled trial that included 22 593 women with cervical cancer met the inclusion criteria. Twenty percent of the studies had <36 months of follow-up, and 24% had more than 60 months of follow-up. The odds of PFS were worse for women undergoing MIS radical hysterectomy (odds ratio 1.54; 95% CI [confidence interval], 1.24-1.94; 14 studies). When limited to studies with longer follow-up, the odds of PFS were progressively worse with MIS radical hysterectomy (HR [hazard ratio] 1.48 for >36 months; 95% CI, 1.21-1.82; 10 studies; HR 1.69 for >48 months; 95% CI, 1.26-2.27; 5 studies; and HR 2.020 for >60 months; 95% CI, 1.36-3.001; 3 studies). For overall survival, the odds were not significantly different for MIS vs abdominal hysterectomy (odds ratio 0.94; 95% CI, 0.66-1.35; 14 studies) (HR 0.99 for >36 months; 95% CI, 0.66-1.48; 9 studies; HR 1.05 for >48 months; 95% CI, 0.57-1.94; 4 studies; and HR 1.35 for >60 months; 95% CI, 0.73-2.51; 3 studies).; Conclusion: In our meta-analysis of 50 studies, MIS radical hysterectomy was associated with worse PFS than open radical hysterectomy for early-stage cervical cancer. The emergence of this finding with longer follow-up highlights the importance of long-term, high-quality studies to guide cancer and surgical treatments. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Smith, R. B., et al. (2021). "Impact of Retained Cystoscopy Fluid after Laparoscopic Hysterectomy: A Randomized Controlled Trial." Journal of Minimally Invasive Gynecology 28(2): 288-296.
	STUDY OBJECTIVE: To investigate the impact of retained cystoscopy fluid after laparoscopic hysterectomy on time to spontaneous void, time to discharge, urinary retention, bladder discomfort, and patient satisfaction. DESIGN: Single-blind randomized controlled trial. SETTING: An academic medical center. PATIENTS: One hundred and twenty patients who underwent laparoscopic hysterectomy with universal cystoscopy for benign indications, excluding pelvic organ prolapse and urinary incontinence indications. INTERVENTIONS: From October 10, 2018, to October 17, 2019, we compared 200 mL retained cystoscopy fluid and complete bladder emptying after laparoscopic hysterectomy with universal cystoscopy. MEASUREMENTS AND MAIN RESULTS: A total of 120 patients were enrolled and randomized (59 in the retained cystoscopy fluid group and 61 in the emptied fluid group). The primary outcome was time to first spontaneous void. The secondary outcomes were time to discharge, urinary retention rates, bladder discomfort, and patient satisfaction. A sample size of 120 was calculated to detect a 57-minute difference in time to spontaneous void. There were minimal differences in baseline demographics and surgical characteristics between the groups. There was an apparent, although not significant, difference in time to void of 25 minutes (143 minutes vs 168 minutes, p = .20). Time to discharge and urinary retention rates did not differ (199 minutes vs 214 minutes, p = .40, and 13.6% vs 8.2%, p = .51, respectively). There was no difference in postoperative bladder discomfort and patient satisfaction. CONCLUSION: Retained cystoscopy fluid after laparoscopic hysterectomy did not significantly affect time to first spontaneous void, time to discharge, urinary retention, bladder discomfort, or patient satisfaction.

Smith, R. D., et al. (2021). "Protocol of a systematic review and network meta-analysis for the prevention and treatment of perinatal depression." BMJ Open 11(10): e048764.
	INTRODUCTION: Perinatal depression is common and can often lead to adverse health outcomes for mother and child. Multiple pharmacological and non-pharmacological treatments have been evaluated against usual care or placebo controls in meta-analyses for preventing and treating perinatal depression compared. It is not yet established which of these candidate treatments might be the optimal approach for prevention or treatment. METHODS AND ANALYSIS: A systematic review and Bayesian network meta-analyses will be conducted. Eight electronic databases shall be searched for randomised controlled trials that have evaluated the effectiveness of treatments for prevention and/or treatment of perinatal depression. Screening of articles shall be conducted by two reviewers independently. One network meta-analysis shall evaluate the effectiveness of interventions in preventing depression during the perinatal period. A second network meta-analysis shall compare the effectiveness of treatments for depression symptoms in women with perinatal depression. Bayesian 95% credible intervals shall be used to estimate the pooled mean effect size of each treatment, and surface under cumulative ranking area will be used to rank the treatments' effectiveness. ETHICS AND DISSEMINATION: We shall report our findings so that healthcare providers can make informed decisions on what might be the optimal approach for addressing perinatal depression to prevent cases and improve outcomes in those suffering from depression through knowledge exchange workshops, international conference presentations and journal article publications. PROSPERO REGISTRATION NUMBER: CRD42020200081.

Snabes Michael, C., et al. (2023). "Phase 2, double-blind, randomized, placebo-controlled study of the safety and efficacy of elagolix in women with polycystic ovary syndrome." F&S reports 4(2): 206-212.
	Objective: Evaluate the efficacy and safety of elagolix, a GnRH antagonist, to treat polycystic ovarian syndrome (PCOS).; Design: A phase 2, multicenter, double-blind, randomized, placebo-controlled trial.; Setting: Outpatient and academic medical centers.; Patients: One hundred fourteen women with PCOS (aged 18-35 years, body mass index 18.5-38 kg/m 2 ).; Interventions: Patients were randomized 2:2:2:2:2:3 to elagolix (25 mg twice daily, 50 mg once daily, 75 mg twice daily, 150 mg once daily, and 300 mg twice daily) or placebo.; Main Outcome Measures: The primary endpoint was menstrual cycle normalization (defined as 2 menstrual cycles 21-35 days in length during the 4-month treatment period). The secondary endpoint was change from baseline to week 1 in the area under the luteinizing hormone (LH) serum concentration-time curve (AUC). Additional endpoints included change from baseline in serum hormone levels.; Results: No significant improvement in restoring normal menstrual cycles was observed in treated subjects; 3 of 114 patients met the primary endpoint. Six patients experienced progesterone elevations indicative of ovulation. The LH levels decreased from baseline to week 16, and LH AUC was significantly reduced from baseline to week 1 in all elagolix treatment groups ( P <.1 vs placebo). Follicle-stimulating hormone (FSH) levels generally remained stable through week 16, with no significant differences in FSH AUCs. Serum estradiol and testosterone concentrations were consistently reduced from baseline in all elagolix dose groups compared with placebo. Adverse event rates were similar across treatment groups.; Conclusions: Elagolix treatment did not normalize the ovulatory cycle in patients with PCOS.; Clinical Trial Registration Number: NCT03951077. (© 2023 The Authors.)

Sniadecki, M., et al. (2019). "New therapeutic approaches in the treatment of node-positive cervical cancer patients based on molecular targets: a systematic review." Ginekologia polska 90(6): 336-345.
	Cervical uterine cancer is the second most frequent female cancer worldwide and a substantial burden for low-income societies and the patients themselves. Understanding the molecular mechanisms of metastasis permits the development of therapies that limit tumor progression, as well as providing health and social benefits. Pathomorphology is still the basis of research and a reference standard for molecular analysis. The aim of our study was to research and critically evaluate clinical trials that use new oncological approaches for node-positive cervical cancer to gain an insight into the molecular mechanisms of tumor metastasis.; Inclusion Criteria: node-positive disease at baseline; at least a first phase clinical study comprising adult female patients; novel clinical approach (e.g., radiotherapy, immunotherapy, targeted therapy, vaccines, radiosurgery); histologic measurement of treatment efficacy (preferably lymph node ultrastaging); and publications in English language only.; Information Sources: US Clinical trials registry, EU Clinical trials register, ISRCTN registry, and Ovid, EBSCO and Cochrane Collaboration databases. Access dates: from January 2010 to April 2018.; Exclusions: Abstracts that did not meet the inclusion criteria or with unreliable data. We collected complete data (e.g., the entire publication associated with included abstracts, heterogeneity examination of individual studies, and validity measurement of the statistical methods used). Results were analyzed in relation to the most recent understanding of the pathogenesis of cervical cancer metastasis. We proposed a possible direction for drug treatment of epithelial tumors based on the mechanisms of metastasis.

Śnieżek, A., et al. (2021). "Physiotherapy according to the BeBo Concept as prophylaxis and treatment of urinary incontinence in women after natural childbirth." Scientific Reports 11(1): 18096.
	Pelvic floor muscle dysfunctions can lead to urinary incontinence, a condition which often affects women both during pregnancy and after childbirth. As a result of this, certain exercises are recommended during and after pregnancy to prevent and treat this incontinence, and the BeBo Concept is one of these methods used to prevent pelvic floor muscle dysfunction. The aim of the present study was to evaluate the effects of a 6-week course of physical therapy according to the BeBo Concept on the improvement of perineal muscle strength and endurance as well as urinary continence in women after their first vaginal delivery. The study was conducted on a group of 56 women who were randomly assigned to the exercise (n = 30) or control (n = 26) group. The exercising group participated in a 6-week physical therapy program according to the BeBo Concept. Pelvic floor muscles were assessed using the perineometer and palpation Perfect Test. UDI6 and ICIQ-SF questionnaires were used to obtain information about the symptoms of urinary incontinence, evaluate the frequency, severity and impact of urine leakage on the quality of life. In all women after natural childbirth, regardless of treatment, it was observed that measured parameters improved, but the improvement was slightly more explicit in those who participated in the Bebo Concept exercise group (e.g. ICIQ-SF exercise group p = 0.001, control group p = 0.035). Due to its positive impact on the pelvic floor, this exercise program should be recommended to women after natural childbirth.

Snipe, R. M. J., et al. (2024). "Omega-3 long chain polyunsaturated fatty acids as a potential treatment for reducing dysmenorrhoea pain: Systematic literature review and meta-analysis." Nutrition & dietetics: the journal of the Dietitians Association of Australia 81(1): 94-106.
	AIM: This systematic literature review with meta-analysis aimed to determine the effect of omega-3 long chain polyunsaturated fatty acids on prostaglandin levels and pain severity in women with dysmenorrhoea and identify adverse side effects. METHOD(S): A literature search was conducted in Embase, Scopus, Web of Science, MEDLINE complete, CINAHL and AMED databases (PROSPERO CRD42022340371). Included studies provided omega-3 long chain polyunsaturated fatty acids compared to a control in women with dysmenorrhoea and reported pain and/or prostaglandin levels. A random effects meta-analysis with Cohen's d effect size (95% confidence interval) was performed in SPPS for studies that reported pain outcomes. Study quality was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. RESULT(S): Twelve studies (n=881 dysmenorrhoeal women) of predominantly neutral quality (83%) were included that provided daily supplementation of 300-1800mg omega-3 long chain polyunsaturated fatty acids over 2 or 3 months. Meta-analysis (n=8 studies) showed a large effect of omega-3 long chain polyunsaturated fatty acids (d=-1.020, 95% confidence interval -1.53 to -0.51) at reducing dysmenorrhoea pain. No studies measured prostaglandin levels, 86% of studies measuring analgesic use showed a reduction with omega-3 long chain polyunsaturated fatty acids and few studies reported mild adverse side effects in individual participants. CONCLUSION(S): Findings suggest that daily supplementation of 300-1800mg omega-3 long chain polyunsaturated fatty acids over 2-3 months are generally well tolerated and reduces pain and analgesic use in women with dysmenorrhoea. However, the neutral quality of research is limited by methodological issues and the mechanism of action remains to be determined.Copyright © 2023 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.

Soares, J. M., et al. (2021). "Systematic review of finasteride effect in women with hirsutism." Revista da Associacao Medica Brasileira 67(7): 1043-1049.
	
Soave, I., et al. (2019). "Pelvic floor muscle training for prevention and treatment of urinary incontinence during pregnancy and after childbirth and its effect on urinary system and supportive structures assessed by objective measurement techniques." Archives of Gynecology and Obstetrics 299(3): 609-623.
	PURPOSE: During the second and the third trimesters of pregnancy and in the first 3 months following childbirth, about one-third of women experience urinary incontinence (UI). During pregnancy and after delivery, the strength of the pelvic floor muscles may decrease following hormonal and anatomical changes, facilitating musculoskeletal alterations that could lead to UI. Pelvic floor muscle training (PFMT) consists in the repetition of one or more sets of voluntary contractions of the pelvic muscles. By building muscles volume, PFMT elevates the pelvic floor and the pelvic organs, closes the levator hiatus, reduces pubovisceral length and elevates the resting position of the bladder. Objective of this review is to evaluate the efficacy of PFMT for prevention and treatment of UI during pregnancy and after childbirth and its effect on urinary system and supportive structures assessed by objective measurement techniques. METHODS: The largest medical information databases (Medline-Pubmed, EMBASE, Lilacs, Cochrane Library and Physiotherapy Evidence Database) were searched using the medical subject heading terms "pelvic floor muscle training", "prevention", "urinary incontinence", "urinary stress incontinence", "objective measurement techniques", "pregnancy, "exercise", "postpartum" and "childbirth" in different combinations. RESULTS AND CONCLUSIONS: Overall, the quality of the studies was low. At the present time, there is insufficient evidence to state that PFMT is effective in preventing and treating UI during pregnancy and in the postpartum. However, based on the evidence provided by studies with large sample size, well-defined training protocols, high adherence rates and close follow-up, a PFMT program following general strength-training principles can be recommended both during pregnancy and in the postnatal period.

Sobel, J., et al. (2022). "Efficacy and Safety of Oral Ibrexafungerp in Subjects with Vulvovaginal Candidiasis: Pooled Data from Two Phase 3, Randomized, Blinded, Study vs. Placebo (VANISH-303 and VANISH-306)." American Journal of Obstetrics and Gynecology 226(2): 290.
	Objectives: Vulvovaginal candidiasis (VVC) affects 75 million women at least once in their lifetime. Historically, there are a limited number of well-controlled treatment studies in the literature comparing an active control to placebo for VVC. Ibrexafungerp (IBX) is a novel oral triterpenoid antifungal in development to treat VVC. IBX is fungicidal with broad in vitro activity against Candida spp., including fluconazole-resistant Candida. We present pooled analysis of outcomes from all subjects in VANISH-303 (V-303) and VANISH-306 (V-306), two large randomized, double blind Phase 3 studies of IBX versus Placebo (PLC) in women with VVC. Method(s): Two multicenter, randomized, double-blind studies were initiated; V-303, in 28 centers in the U.S. and V-306 with centers in U.S. (19) and Bulgaria (18). Patients (age 12 years and older) were randomized to oral IBX (one-day 600mg dose given as two 300mg doses 12 hours apart) or matching PLC in a 2:1 ratio. Eligible patients had to present with an episode of VVC with vulvovaginal signs and symptoms (VSS) score >=4. Primary efficacy population was the modified-intent-to-treat (mITT), comprised of subjects with culture confirmed Candida spp. infection at baseline who received at least one dose of study treatment. The primary endpoint was Clinical Cure, defined as complete resolution (score of 0) of all VSS at the Day-10 test-of-cure (TOC) visit. Result(s): Pooled MITT group in VANISH studies included 376 subjects (188 in V-303, 188 in V-306) in the IBX arm and 182 subjects (98 in V-303, 84 in V-306) in the PLC arm. Primarily women with severe VVC at baseline (VSS>7, 94% on IBX and 92% on PLC) were enrolled. The Clinical Cure at TOC for IBX was 56.9%, significantly superior (p=0.001) to PLC, 35.7%. The secondary endpoint of clinical improvement for IBX and PLC (VSS <=1) at TOC was 72.9% vs. 52.2%, respectively (p<0.001) and mycological eradication at TOC was 54.0% and 24.2%, respectively (p<0.001). Adverse events for IBX were predominantly gastrointestinal with mild to moderate, diarrhea (16.7%), nausea (11.9%) and abdominal pain (8.3%) being the most common, most lasting 1 day. Conclusion(s): These results provide further evidence of the therapeutic potential of one-day dose of oral IBX for the treatment of women diagnosed with moderate and severe VVC.Copyright © 2021

Soderhamn, B., et al. (2022). "Impact of letrozole cO-treatment during ovarian stimulation on the oocyte yield, embryo development, and live birth rate - a randomised controlled trial (RIOT)." Human Reproduction 37(Supplement 1): i73.
	Study question: Does letrozole co-treatment during ovarian stimulation for in vitro fertilization (IVF) impact oocyte yield, embryo development, and live birth rate (LBR) in expected normal responders? Summary answer: Letrozole co-treatment leads to similar oocyte yield, embryo- development and utilisation rate, and live birth rate after transfer in the fresh cycle. What is known already: Letrozole reduces oestradiol levels by inhibiting the aromatization of androgens, this diminishes pituitary suppression and increases endogenous gonadotrophin release. These effects are utilized in ovulation induction in PCOS patients and may benefit certain patients during IVF treatment. In addition, we have recently reported in an RCT that cotreatment with letrozole increases luteal phase progesterone levels and, consistent with previous studies, no significant effect on pregnancy rates was observed. However, the impact of the changes in the endocrine milieu caused by letrozole co-treatment on the developing oocytes and embryos remains unclear as most published studies are retrospective and lack appropriate control- groups. Study design, size, duration: A multicentre double-blinded randomised placebo-controlled trial was conducted in four fertility clinics at University Hospitals in Denmark from August 2016 to November 2018. 159 women were randomised, 129 women received single embryo (cleavage stage or blastocyst) transfer in the fresh cycle, and the surplus 257 embryos were vitrified. The study was conducted following the Helsinki Declaration and the ICH-Good-Clinical-Practice. Data collection and reporting followed the guidelines of CONSORT to achieve transparent reporting of trials. Participants/materials, setting, methods: Women with expected normal ovarian response received an antagonist protocol with fixed-dose FSH. Cotreatment consisted of 5mg letrozole or placebo from the start of stimulation until the day of triggering final oocyte maturation with hCG. Standardized morphological evaluation was performed at all centres (applying the Istanbul consensus and Gardner-score). A sub-cohort of the embryos were cultured in an EmbryoScope incubator and further assessed by morphokinetic annotation and reported with.KIDScoreD3. Ongoing pregnancies were followed until birth. Main results and the role of chance: A total of 1268 oocytes were retrieved from 154 women, leading to development of 386 usable embryos that were either transferred or vitrified. Utilisation rate (the proportion of usable embryos to oocytes) was similar in the letrozole group and placebo group with 0.31 vs. 0.36 (mean difference (MD): -0.05, 95% CI[-0.03;0.12], P=0.25). Morphologically grading the embryos as good, fair, and poor quality showed similar results, the odds of having a higher quality were 0.78 times higher in the letrozole- vs. placebo group (CI[0.5;1.1], P=0.2). Morphokinetic annotations (n=302 embryos) showed similar results with the odds of having a high KIDScore3 1.3 times higher in the letrozole - vs. placebo group (CI[0.9;2.1], P=0.2). The endometrial thickness at transfer was thinner in the letrozole compared to the placebo group with 8.5 vs. 9.5mm (MD 1.0, 95% CI[0.4;1.6], P=0.001) but with the same ultrasonic echogenicity and a preovulatory three-layer appearance. After embryo transfer in the fresh cycle (n=129), no differences were seen in the pregnancy outcomes: positive serum hCG, ongoing pregnancy rate, early miscarriage rate, foetal miscarriage rate, or LBR. LBR per initiated cycle were similar as well (n=159): 23.8% vs. 29.1% (MD of -5,3%, CI[-20.3%;9.6%], P=0.48) in letrozole vs. placebo group, respectively. Limitations, reasons for caution: Four clinics participating could lead to interobserver variability. However, bias was reduced by block-randomised design. All data are derived from an RCT, the primary endpoint of which, preovulatory progesterone, was the basis of the sample size calculation. The study may have been underpowered to show a significant impact on LBR. Wider implications of the findings: Letrozole co-treatment during ovarian stimulation with gonadotrophins did not have an impact on the oocyte yield and embryo development. These data suggest that letrozole co-treatment is unlikely to compromise outcomes in its growing indications: ovulation induction, IVF in poor responders, and fertility preservation in breast cancer patients.

Sofia Andrade De, O. and M. Priscila (2022). "Infertility and endometrioma: cystectomy before IVF or not? Systematic review and meta-analysis."
	
Sofiane, B., et al. (2023). "Recurrence after surgical management of colorectal endometriosis : update."
	
Sofiane, B., et al. (2023). "Voiding dysfunction after surgical management of colorectal endometriosis."
	
Sofy Ahmed, A. and S. Tsui (2023). "Comparison of polyvinyl alcohol particles and tris-acryl gelatin microspheres embolic agents used in uterine artery embolization: A systematic review and meta-analysis." Turkish Journal of Obstetrics and Gynecology 20(1): 74-84.
	Objective: To identify the preferred agent by comparing the therapeutic efficacy, degree of infarction, and side effects of polyvinyl alcohol particles (PVA) and tris-acryl gelatin embolization (TAGM) agents in uterine artery embolization.; Materials and Methods: We included available articles comparing PVA with TAGM embolization agents in the management of fibroids. The primary outcomes included the decrease in uterine volume (%), decrease in dominant tumor volume (%), fibroid infarction rate, complete infarction fibroid, complications, pain score after 24 h, procedure time (minutes), duration of hospital stay, fluoroscopy time (minutes), and the change in symptom severity score.; Results: Eight articles that met our inclusion criteria were included in this study. Our analysis yielded an overall superiority of PVA compared to TAGM regarding complete fibroid infarction rate at the first 24 h. However, TAGM was better than PVA concerning <90% infarction rate outcome. While both embolization techniques showed similar effects regarding the change in symptom severity score, the percentage of decrease in uterine volume, percentage of decrease of dominant tumor volume, 90-99% infarction rate, complete infarction rate when assessed after the first 24 h, pain score after the first 24 h, procedure time, fluoroscopy time, minor, and major complications.; Conclusion: Both PVA and TAGM embolization agents are effective and safe modalities in treating patients with fibroids, with no significant variation of both agents in most outcomes.; Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors. (©Copyright 2023 by Turkish Society of Obstetrics and Gynecology | Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.)

Soheila, N., et al. (2023). "Effect of oral and topical ginger on primary dysmenorrhea: a systematic review."
	
Soheili, M., et al. (2021). "Human papilloma virus: A review study of epidemiology, carcinogenesis, diagnostic methods, and treatment of all HPV-related cancers." Medical journal of the Islamic Republic of Iran 35: 65.
	Background: Human papillomavirus (HPV) infection is considered as the most common viral sexually transmitted infection worldwide. This poses an increasingly interdisciplinary medical challenge. Since there is vast scattered information in databases about HPV and the correlated diseases, we decided to collect useful data so that the experts can get a more comprehensive view of HPV. Methods: In this article, HPV-associated diseases, prevalence, prevention, and new treatments are discussed. The retrieved articles reporting the latest data about the required information for our review were selected through searching in Web of Science, Scopus, Medline (PubMed), EMBASE, Cochrane Library, Ovid, and CINHAL with language limitations of English and German. Results: There are 2 groups of HPVs: (1) low-risk HPV types that can lead to genital warts, and (2) high-risk HPV types that are involved in HPV-associated oncogenesis. About 70% of all sexually active women are infected and most of these infections heal within many weeks or months. In the case of HPV-persistence, a risk of preneoplasia or carcinoma exists. These types of viruses are responsible for the existence of genitoanal, gastrointestinal, urinary tract, and head and neck tumors. There is still no definite successful treatment. The detection of HPV-related condylomata occurs macroscopically in women and men, and the diagnosis of the precursors of cervical carcinoma in women is possible by Pap smear. Conclusion: For extragenital manifestations, there is no structured early detection program. Meanwhile, studies on HPV vaccines confirm that they should be used for the primary prevention of HPV-dependent diseases. However, we need more research to find out the real advantages and disadvantages of vaccines.

Sohl, S. J., et al. (2023). "A randomized pilot of eHealth mindful movement and breathing to improve gynecologic surgery outcomes." Journal of Psychosocial Oncology 41(3): 251-266.
	Objective: To conduct a pilot randomized controlled trial of eHealth Mindful Movement and Breathing (eMMB) compared to an empathic attention control (AC). Participant(s): Women undergoing surgery for a suspected gynecologic malignancy. Method(s): eMMB is a brief yoga intervention delivered remotely during the perioperative timeframe. We assessed feasibility and participants completed assessments (baseline, weeks 2 and 4 postoperatively). We summarized feasibility, participant characteristics, and outcomes by intervention group and time. Finding(s): Forty-three percent of eligible patients approached participated (n = 31). Adherence to the interventions was 77%. Percent of participants to complete outcomes was 81% at Week 2 and 84% at Week 4 (>70%; retention was the primary feasibility indicator). Average reductions in the primary outcome of pain intensity were larger in the eMMB group than AC group (Week 2 d = -0.38; Week 4 d = -0.46). Implications: This pilot study of eMMB supported feasibility and improvements in pain intensity that warrant a future efficacy study.Copyright © 2022 Taylor & Francis Group, LLC.

Sohrevardi, S. M., et al. (2021). "Therapeutic Effect of Curcumin in Women with Polycystic Ovary Syndrome Receiving Metformin: A Randomized Controlled Trial." Advances in experimental medicine and biology 1308: 109-117.
	Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically. It has been shown that curcumin also exhibits insulin-sensitizing properties. Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome. This clinical trial was conducted on 100 women with PCOS, diagnosed according to the Rotterdam criteria, who were sequentially recruited and randomly divided into two groups (n = 50 each). Group 1 received 500 mg metformin three times daily and group 2 received 80 mg/day capsule of curcumin nanomicelle and 500 mg metformin three times a day for 3 months. After collecting fasting blood samples, biochemical parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, plasma glucose, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were evaluated based on enzymatic methods. Hormonal parameters were assessed using immunoassay kits. Insulin resistance (HOMA-IR) and insulin-sensitivity check index (QUICKI) were also assessed. After treatment, fasting insulin, HOMA-IR, and total testosterone in group 2 were significantly lower than those in group 1 (p < 0.05). Post-treatment LDL-C levels in groups 1 and 2 were 117.9 ± 24 and 91.12 ± 19.46 mg/dL, respectively (p < 0.01). In addition, HDL-C levels were increased with curcumin (group 1: 38.1 ± 4.36 mg/dL; group 2: 44.12 ± 7.3 mg/dL, p < 0.05). Total cholesterol was decreased with curcumin level (group 1: 207.9 ± 39.84 mg/dL; group 2; 159.7 ± 48.43 mg/dL, p < 0.05), with a decrease in triglycerides levels (group 1: 141.6 ± 9.57; group 2: 97.5 ± 8.8 mg/dL, p < 0.01). This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS. Therefore, the combined use of metformin and curcumin may have therapeutic utility in patients with PCOS.

Soldat-Stankovic, V., et al. (2021). "THE EFFECT OF MYOINOSITOL AND METFORMIN ON CARDIOVASCULAR RISK FACTORS IN WOMEN WITH POLYCYSTIC OVARY SYNDROME: A RANDOMIZED CONTROLLED TRIAL." Acta endocrinologica (Bucharest, Romania : 2005) 17(2): 241-247.
	CONTEXT: Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? OBJECTIVE: To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). DESIGN: Open label, parallel randomized, single center study. SUBJECTS AND METHODS: Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. RESULTS: Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. CONCLUSIONS: Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

Soldat-Stanković, V., et al. (2022). "The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial." Journal of endocrinological investigation 45(3): 583-595.
	Purpose: To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI).; Methods: In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment.; Results: After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014).; Conclusion: Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women.; Trial Registration: ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered. (© 2021. Italian Society of Endocrinology (SIE).)

Sole-Sedeno Josep, M., et al. (2023). "Protein Supplementation in a Prehabilitation Program in Patients Undergoing Surgery for Endometrial Cancer." International Journal of Environmental Research and Public Health 20(8).
	Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways to reduce stress response and improve perioperative outcomes, which also include nutritional interventions. The aim of this study is to assess the impact of protein supplementation with 20 mg per day before surgery in a prehabilitation program in postoperative serum albumin, prealbumin, and total proteins in endometrial cancer patients undergoing laparoscopic surgery.; Methods: A prospective study including patients who underwent laparoscopy for endometrial cancer was conducted. Three groups were identified according to ERAS and prehabilitation implementation (preERAS, ERAS, and Prehab). The primary outcome was levels of serum albumin, prealbumin, and total protein 24-48 h after surgery.; Results: A total of 185 patients were included: 57 in the preERAS group, 60 in the ERAS group, and 68 in the Prehab group. There were no basal differences in serum albumin, prealbumin, or total protein between the three groups. After surgery, regardless of the nutritional intervention, the decrease in the values was also similar. Moreover, values in the Prehab group just before surgery were lower than the initial ones, despite the protein supplementation.; Conclusions: Supplementation with 20 mg of protein per day does not impact serum protein levels in a prehabilitation program. Supplementations with higher quantities should be studied.

Soliman, A., et al. (2023). "How autologous platelet-rich plasma affects pregnancy and birth outcomes in women with repeated embryo implantation failure: A prisma-compliant meta-analysis." Turkish Journal of Obstetrics and Gynecology 20(2): 154-163.
	Repeated implantation failure refer to failure to conceive after three or more embryo transfer attempts. Several interventions were offered to improve maternal and fetal outcomes. Our objective was to investigate the impact of platelet-rich plasma (PRP) as a promising intervention to improve both pregnancy and birth outcomes. We searched PubMed, Scopus, Web of Science, and Cochrane Central, in addition to other relevant resources of grey literature. Only clinical trials were eligible to be included. We performed the meta-analysis using a random effects model. Eight randomized clinical trials, enrolling 1038 women with more than 3 implantation failure attempts, were included. We found a significant increase regarding all our prespecified primary outcomes. Chemical pregnancy rate [relative ratio (RR): 1.96, 95% confidence interval (CI): 1.61, 2.39; p<0.001], clinical pregnancy rate (RR: 4.35, 95% CI: 1.92, 2.88; p<0.001), and live birth rate (RR: 4.03, 95% CI: 1.29, 12.63; p=0.02) were found to be statistically significant and increased in patients who received PRP compared with the control group. Implantation rate (RR: 1.98, 95% CI: 1.34, 2.75; p<0.001), miscarriage rate (RR: 0.44, 95% CI: 0.23, 0.83, p=0.01), and multiple pregnancy rate (RR: 2.56, 95% CI: 1.02, 6.42, p=0.04) were also found to be significantly increased in the PRP group. We provide strong evidence on how intrauterine PRP can improve implantation, pregnancy, and birth outcomes in RIF women, which should direct clinicians to consider this intervention as a very effective tool in assisted reproductive techniques.; Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors. (©Copyright 2023 by Turkish Society of Obstetrics and Gynecology | Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.)

Soliman, P., et al. (2023). "Exploring the utility of liquid biopsy (ctDNA) as a translational endpoint in clinical trials for endometrial cancer (012)." Gynecologic Oncology 176(Supplement 1): S10.
	Objectives: Biomarker predictors of response are incorporated into most modern treatment trials for recurrent endometrial cancer. Invasive procedures for tissue acquisition are often required for baseline assessment of molecular markers, making on-treatment biopsies more challenging. In this study, we explored the incidence of genetic mutations in pre-treatment biopsies, their correlation with pre-treatment ctDNA, and the change in mutation allele frequency (MAF) with therapy among women on an ongoing phase II trial. Method(s): Women enrolled in a phase II randomized trial of everolimus and letrozole +/- ribociclib underwent a baseline tissue biopsy prior to therapy. A subgroup of participants also underwent ctDNA analysis using the Liquid Biopsy 70 (LBP70) Guardant panel at two time points; pre-treatment and after 2 cycles (C3D1, 8 weeks). A MAF of >=0.3 was used to determine clinical relevance. The correlation between mutations identified by next-generation sequencing (NGS) in tissue and pre-treatment ctDNA was assessed. Changes in mutation burden were assessed 8 weeks after initiation of therapy. Result(s): Thirty-two patients were included in the analysis, 14 on everolimus and letrozole (control) and 16 on everolimus, letrozole, and ribociclib (experimental arm). The median number of cycles completed at the time of analysis was 6 (2-28). Best overall response (BOR) was stable disease in 19 (70%), partial response in 6 (22%), and progressive disease in 2 (7%). By NGS of tissue, the most common mutations were PTEN (68%), CTNNB1 (46%), PIK3CA (43%), ARID1A (36%), and KRAS (21%). In these patients, the same mutation was detected by ctDNA: PTEN 76%, CTNNB1 64%, PIK3CA 88%, ARID1A 62%, and KRAS 60%. The overall correlation between clinically relevant NGS tissue mutations and ctDNA detection was 72%. All 6 responders had mutations in the PTEN/AKT pathway on NGS (Table 1). Three of the six (50%) PTEN/AKT mutations were detected on pre-treatment ctDNA, all of which were cleared on follow-up ctDNA. Conclusion(s): In this exploratory study, pre-treatment ctDNA correlated with baseline tissue biopsy suggesting that less invasive techniques can be used to identify translational biomarkers in clinical trials. Among responders with mutations detected on NGS, 50% were also detected in pre-treatment ctDNA, all of which were cleared on C3D1 associated with response to therapy. Further study is warranted to determine if ctDNA can be used to monitor disease response while on treatment. [Formula presented]Copyright © 2023

Solmaz, S., et al. (2022). "The Effect of Education on Women&#39;s Menopause Awareness and Symptom Management: Systematic Review."
	
Somigliana, E., et al. (2021). "Single oral dose of vitamin D3 supplementation prior to in vitro fertilization and embryo transfer in normal weight women: the SUNDRO randomized controlled trial." American Journal of Obstetrics and Gynecology 225(3): 283.e281‐283.e210.
	Background: Improving in vitro fertilization success is an unmet need. Observational studies have suggested that women with deficient or insufficient vitamin D have lower chances of in vitro fertilization success, but whether supplementation improves clinical pregnancy rate remains unclear. Objective: This study aimed to determine whether oral vitamin D3 supplementation improves clinical pregnancy in women undergoing an in vitro fertilization cycle. Study Design: The “supplementation of vitamin D and reproductive outcome” trial is a 2‐center randomized superiority double‐blind placebo‐controlled trial. Subjects were recruited between October 2016 and January 2019. Participants were women aged 18 to 39 years with low vitamin D (peripheral 25‐hydroxyvitamin D of <30 ng/mL), serum calcium of ≥10.6 mg/dL, body mass index of 18 to 25 kg/m2, and antimüllerian hormone levels of >0.5 ng/mL and starting their first, second, or third treatment cycle of conventional in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was the cumulative clinical pregnancy rate per cycle. Pregnancies obtained with both fresh or frozen embryo transfers were included. Clinical pregnancy was defined as an intrauterine gestational sac with a viable fetus. The primary analysis was performed according to the intention‐to‐treat principle and could also include natural conceptions. Secondary outcomes included total dose of gonadotropins used, embryologic variables (number of oocytes retrieved, number of suitable oocytes retrieved, fertilization rate, and rate of top‐quality embryos), and clinical outcomes (miscarriage rate and live birth rate). Results: Overall, 630 women were randomized 2 to 12 weeks before the initiation of the in vitro fertilization cycle to receive either a single dose of 600,000 IU of vitamin D3 (n=308) or placebo (n=322). Interestingly, 113 (37%) and 130 (40%) women achieved a clinical pregnancy in the treatment and placebo groups, respectively (P=.37). The risk ratio of clinical pregnancy in women receiving vitamin D3 was 0.91 (95% confidence interval, 0.75–1.11). Compared with the placebo, vitamin D3 supplementation did not improve the rate of clinical pregnancy. Exploratory subgroup analyses for body mass index, age, indication to in vitro fertilization, ovarian reserve, interval between drug administration and initiation of the cycle, and basal levels of 25‐hydroxyvitamin D failed to highlight any clinical situation that could benefit from the supplementation. Conclusion: In women with normal weight with preserved ovarian reserve and low vitamin D levels undergoing in vitro fertilization cycles, a single oral dose of 600,000 IU of vitamin D3 did not improve the rate of clinical pregnancy. Although the findings do not support the use of vitamin D3 supplementation to improve in vitro fertilization success rates, further studies are required to rule out milder but potentially interesting benefits and explore the effectiveness of alternative modalities of supplementation.

Son, W.-H., et al. (2023). "Moderate intensity walking exercises reduce the body mass index and vascular inflammatory factors in postmenopausal women with obesity: a randomized controlled trial." Scientific Reports 13(1): 20172.
	Postmenopause, the secretion of female hormones changes, causing excessive fat accumulation in the body and leading to chronic inflammation, which increases the incidence of cardiovascular diseases (CVD). Walking is an easily accessible daily exercise and effective non-pharmacological treatment for reducing obesity and the incidence of CVD. The aim of this study was to investigate the effect of moderate intensity walking exercises on body composition, vascular inflammatory factors, and vascular endothelial growth factor (VEGF) in postmenopausal women with obesity. Twenty-six older postmenopausal women with obesity (ages 68-72) were randomly assigned to control (n = 12, BMI 26.06 ± 1.37) or exercise (n = 14, BMI 26.04 ± 1.94) groups. Following a 12-week moderate intensity walking exercise program, we measured the participants' body composition with an InBody S10 analyzer and assessed blood sera using enzyme-linked immunosorbent assays. There was a significant clustering by weight (p < 0.01), body mass index (p < 0.01), percentage body fat (p < 0.001), high-sensitivity C-reactive protein (p < 0.05), interleukin-6, and tumor necrosis factor-α (p < 0.05) being significantly decreased in the exercise group. Although VEGF levels did not change significantly, a tendency to increase was observed in participants that exercised. Our results indicate that walking exercise may help prevent CVD in postmenopausal women with obesity by reducing obesity and vascular inflammatory factors. (© 2023. The Author(s).)

Son, W. M. and J. J. Park (2021). "Resistance Band Exercise Training Prevents the Progression of Metabolic Syndrome in Obese Postmenopausal Women." Journal of sports science & medicine 20(2): 291‐299.
	Metabolic syndrome (MetS) is classified as a combination of risk factors for cardiovascular disease (CVD), and postmenopausal women are specifically at an increased risk for MetS, in part due to the hormonal and metabolic changes that occur at the menopause transition. It is crucial to combat the components of MetS with appropriate lifestyle interventions in this population, such as exercise. This study aimed to examine the effects of a resistance band exercise training program in obese postmenopausal women with MetS. A total 35 postmenopausal women were randomly assigned to either a control group (CON, n = 17) or a resistance band exercise training group (EX, n = 18). Participants in the EX group trained 3days/week. Levels of blood glucose, insulin, homeostatic model of insulin resistance (HOMA‐IR), blood lipid profile, anthropometrics, and blood pressure (BP) were measured at baseline and after the exercise intervention. There were significant group by time interactions (p < 0.05) for blood glucose (Δ‐4.5 mg/dl), insulin (Δ ‐1.3 μU/ml), HOMA‐IR (Δ ‐0.6), triglycerides (Δ ‐9.4 mg/dl), low‐density lipoprotein cholesterol(Δ ‐10.8 mg/dl), systolic BP(Δ ‐3.4 mmHg), body fat percentage (Δ ‐3.0 %), and waist circumference (Δ ‐3.4 cm), which significantly decreased (p < 0.05), and lean body mass (Δ 0.7 kg) and high‐density lipoprotein cholesterol (Δ 5.1 mg/dl), which significantly increased (p < 0.05) after EX compared to no change in CON. The present study indicates that resistance band exercise training may be an effective therapeutic intervention to combat the components of MetS in this population, potentially reducing the risk for the development of CVD.

Song, B., et al. (2020). "TVT-O vs TVT-S for female stress urinary incontinence: A systematic review and meta-analysis." International Journal of Clinical Practice 74(9): e13506.
	Background: Tension-free vaginal tape obturator (TVT-O) and tension-free vaginal tape secur (TVT-S) are common surgeries for the treatment of stress urinary incontinence (SUI), several randomised controlled trials (RCTs) have compared the effects of TVT-O and TVT-S, yet the results remained inconsistent. Therefore, we attempted to conduct this systematic review and meta-analysis to analyse the role of TVT-O and TVT-S in patients with SUI. Method(s): We searched PubMed databases from inception date to Jan 15, 2020 for RCTs that compared TVT-O and TVT-S in SUI patients. Two authors independently screened and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MD) with 95% confidence intervals (95% CI) were calculated for each outcome by fixed- or random-effects model. Result(s): Seven RCTs with a total of 755 patients were identified, with 373 patients for TVT-O and 382 patients for TVT-S. TVT-O preceded TVT-S in the objective cure at 12 months (OR = 1.72, 95% CI 1.21-2.45), subjective cure (OR = 1.98, 95% CI 1.08-3.62); but TVT-S have more advantage in the incidence of postoperative thigh pain (OR = 18.94, 95% CI 7.01-51.15); no significant differences on the duration of operative procedure (OR = -1.09, 95% CI -2.37-0.18), urinary retention (OR = 0.77, 95% CI 0.36-1.62) and urinary infection (OR = 1.80, 95% CI 0.63-5.13) were found. Conclusion(s): TVT-O should be preferred for patients with SUI even though with higher risks of postoperative thigh pain when compared with TVT-S, more related studies are needed to identify the role of TVT-O and TVT-S for the treatment of SUI.Copyright © 2020 John Wiley & Sons Ltd

Song, B.-H. and J. Kim (2023). "Effects of Pilates on Pain, Physical Function, Sleep Quality, and Psychological Factors in Young Women with Dysmenorrhea: A Preliminary Randomized Controlled Study." Healthcare (Basel, Switzerland) 11(14).
	The effect of Pilates on dysmenorrhea has been little studied. The purpose of this study was to evaluate the effect of Pilates on menstrual pain and symptoms, premenstrual syndrome, and risk factors of dysmenorrhea. Thirty young women with primary dysmenorrhea were randomly assigned into a Pilates group (PG; n = 15) and a waitlist control group (CG; n = 15). The Pilates was performed twice a week for 12 weeks. Menstrual pain and symptoms were measured by visual analogue scale (VAS) and the Cox menstrual symptom scale (CMSS), respectively. Premenstrual syndrome was assessed using the premenstrual symptoms screening tool (PSST). Additionally, back flexibility, hip muscle strength, sleep duration and quality, perceived stress, state-trait anxiety, and depression were evaluated. The VAS, CMSS severity and frequency, and PSST symptoms and functional impairments decreased in the PG compared to the CG ( p < 0.001 or p < 0.01) with large effect sizes. Back flexibility and the strength of hip flexors, hip extensors, and hip abductors significantly increased in the PG compared to the CG (all p < 0.01) with large effect sizes. Sleep quality ( p < 0.01) and stress ( p < 0.05) improved in the PG. Sleep duration, anxiety, and depression did not change in either group. In conclusion, the 12-week Pilates intervention ameliorates dysmenorrhea, partly mediated by improved physical function and sleep quality.

Song, X., et al. (2022). "The relationship between hormone repalcement and ovarian caner."
	
Song, Y., et al. (2021). "Effects of Metformin and Exercise in Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis." Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 53(11): 738-745.
	Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metformin is introduced for treatment of women with PCOS, and the beneficial effects of exercise in women with PCOS are found for a range of outcomes. Our aim is to compare the effects of metformin plus exercise with exercise intervention in PCOS on clinical, anthropometric, metabolic, and psychological parameters. MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. Nine studies were considered eligible for inclusion. The meta-analysis reveals that metformin offers additive benefits to exercise, leading to modest improvements in menstrual cycles, hyperandrogenism, and abdominal fat.; Competing Interests: The authors declare that they have no conflicts of interest. (Thieme. All rights reserved.)

Song, Y. and F. Zhao (2024). "Effect of initial treatment with chemotherapy or surgery on wound complications in patients with advanced ovarian cancer: A meta-analysis." International wound journal 21(2): e14722.
	There has been controversy over the use of neoadjuvant chemotherapy or surgery in the treatment of ovarian cancer. The purpose of this meta-analysis is to assess the hazard evaluation of the effect of adjuvant chemotherapy over primary debulking surgery (PDS) on the incidence of wound infection in women with ovarian carcinoma. In this research, we looked at PubMed, Embase and Cochrane Library to evaluate the impact of PDS and chemotherapy on the incidence of wound infections in women with ovarian cancer. Based on the keywords of 'Ovary Cancer', 'Surgical' and 'Chemotherapy', we looked up the data in the digital database, and at last, we selected six of them from 1453 studies. There was no time limitation in the studies. The meta-analyses included studies that described the risk factors of wound infection in ovarian carcinoma patients, particularly those who reported OR value. The Chi-square method was employed to perform statistical analysis of the inter-study heterogeneity, with additional analyses dependent on I2. A sensitivity analysis was conducted, and a possible publication bias was evaluated. The findings suggest that there is a significant reduction in the rate of wound infections among patients with ovarian cancer treated with primary chemotherapy than with PDS (OR, 2.80; 95% CI, 1.79, 4.39, p < 0.0001). There was a significant reduction in the incidence of thrombus in patients with ovarian cancer who were treated with primary chemotherapy than in those who did have prior surgical intervention (OR, 2.77; 95% CI, 1.34, 5.74, p = 0.006). Our findings indicate that early chemotherapy in ovarian cancer patients may lower their chances of developing wound infection.Copyright © 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Song, Y.-J., et al. (2019). "[Network meta-analysis on the effects of the acupuncture-related therapy on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome]." Zhongguo zhen jiu = Chinese acupuncture & moxibustion 39(7): 792-798.
	Objective: To review systematically the safety and effectiveness of acupuncture-related therapies on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome (PCOS).; Methods: From PubMed, EMbase, the Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database, the randomized controlled trials (RCTs) on PCOS were retrieved in the period from the date of database establishment to January 8, 2018. Two researchers screened the articles, extracted the data and assessed the bias risk of the eligible trials independently. Using Stata 13.0 and WinBUGS 1.4.3 software, the data were analyzed.; Results: A total of 39 RCTs were collected, including 4605 cases of PCOS and 14 kinds of acupuncture-related therapies and the comprehensive therapies. The short-term therapeutic effects were observed. The results of mesh meta-analysis showed: regarding the ovulation rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupoint thread-embedding therapy and medication (93.3%), the treatment with moxibustion and Chinese herbal medicine (91.4%), moxibustion (74.5%), the treatment with acupuncture and medication (65.7%), the treatment with acupuncture-moxibustion and auricular point therapy (61.9%) and the treatment with acupuncture and auricular point therapy (49.6%). Regarding the pregnancy rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupuncture and auricular point therapy (91.5%), the treatment with moxibustion and Chinese herbal medication (86.9%), the treatment with acupuncture-moxibustion and auricular point therapy (81.1%), the treatment with acupoint thread-embedding therapy and medication (69.4%), the treatment with acupuncture and medication (66.1%) and the treatment with placebo and western medication (58.7%).; Conclusion: Among acupuncture-related therapies, the combined treatment is more advantageous than single therapy and its safety is superior to western medication. The combined therapies are various in advantages. Because of the limitation of the present researches, it needs a large scale of RCTs with rational design, high quality and proper methods to verify this research conclusion.

Song, Z., et al. (2023). "Assessing the role of robotic surgery versus laparoscopic surgery in patients with a diagnosis of endometriosis: A meta-analysis." Medicine 102(50): e33104.
	Background: Surgical management of endometriosis can be carried out with the traditional standard laparoscopic technique or the robotic surgery technique; however, it is not clear if there is a significant difference between techniques. This meta-analysis aims to evaluate and compare the impact of robotic and standard laparoscopic techniques in endometriosis regarding the clinical outcome.; Methods: Studies comparing robotic surgery to laparoscopic surgery for endometriosis were among the studies from various languages that met the inclusion criteria. Using dichotomous and continuous random-effect models, the results of these investigations (surgery time, hospitalization time, blood loss, complications, and conversion rate) were examined, and the mean difference with 95% confidence intervals was computed.; Results: Eight studies from 2013 to 2022 were selected for the current analysis including 1741 patients with endometriosis. The studied data revealed a statistically significant (P = .01) lower operation time related to laparoscopic surgery compared with the robotic technique. In addition, the hospitalization time of laparoscopic surgery is significantly (P = .03) lower than that of robotic surgery. On the other hand, blood loss, rehospitalization, postoperative and intraoperative complications, and conversion rates were not significantly different between both techniques. Heterogeneity values were variable according to the analysis factor, from 0% to 91%.; Conclusion: Both robotic and standard laparoscopic techniques have similar outcomes regarding blood loss, rehospitalization, conversion rate, and rate of complication. However, the substantial difference between techniques was in favor of standard laparoscopic surgery regarding operation and hospitalization time.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Soni, P. and D. Desai (2021). "Effectiveness of Pilates and Self-Stretching Exercise on Pain and Quality of Life in Primary Dysmenorrhea" - A Comparative Study." Indian journal of physiotherapy & occupational therapy 15(3): 129‐138.
	Background: Dysmenorrhea, defined as painful cramps that occur with menstruation that prevents a woman from performing normal activities. Incidence of Primary dysmenorrhea is very high among the females of reproductive age group. It is responsible for the school, college and work absenteeism because of pain and discomfort. Objective: The aim of the study was to find out the effectiveness of Pilates and self-stretching on pain and quality of life in primary dysmenorrhea.Methodology: In this study 38 female subjects meeting inclusion criteria were selected. Subjects were randomly divided into two groups. Group – A was treated with Pilates and Group – B was treated with Self-stretching. Both interventions were given for 30 minutes for 3 days per week for 4 weeks. To assess pain intensity Visual Analogue Scale was used and to assess quality of life Menstrual Distress Questionnaire was used. Both the outcome measures were assessed before and after treatment on the day of maximum pain intensity of menstrual cycle. Result: Parametric tests were used for statistical analysis.Within group analysis showed statistically significant reduction in pain and improvement in quality of life in both the groups (p≤ 0.005). Between groups analysis showed statistically significant reduction in pain (p≤0.005) in group A (Pilates) and no significant changes were found in quality of life. Conclusion: Pilates and Self-stretching both interventions are effective in relieving pain and improving quality of life in primary dysmenorrhea. Pilates was found superior to Self-stretching in relieving pain.Key Words: Dysmenorrhea, Pilates, Self – stretching, VAS, MDQ

sonia, s., et al. (2023). "Platelet-Rich plasma as a potential new strategy on the ovarian rejuvenation and pregnancy outcomes in women with primary ovarian insufficiency: A systematic review and meta-analysis."
	
Sonmezer, E., et al. (2022). "Investigation of the Effectiveness of a Pelvic Floor Muscle Training Mobile Application in Women with Stress Urinary Incontinence: Randomized Controlled Trial." International Urogynecology Journal 33(Supplement 2): S490-S491.
	Introduction: It has been reported that pelvic floor muscle training (PFMT) treatment is the most effective treatment with evidence A level in SUI. However, problems in adherence to exercise are the biggest obstacle to the success of PFMT today. Exercise diaries or reminders are used to increase this compliance, but their usability in daily life is controversial. Objective(s): The aim of this study is to develop a PFMT mobile application for individuals with urinary incontinence and to examine its effectiveness on incontinence symptoms and quality of life in women with SUI. Method(s): 26 volunteer women who were diagnosed with SUI were randomly divided into two groups as mobile application and control group. This mobile health application software was developed by the research physiotherapist monitors the patient's body mass index and records the amount of fluid that should be taken during the day. The exercise program determined by the physiotherapist is saved in the application, and it sends an audible notification to the patients to remember the exercises during the day. It records the number of exercises performed by the patient. In addition, this application also includes a notification system that sends lifestyle changes recommendations to patients to reduce urinary incontinence episodes during the day. A 6-week pelvic floor rehabilitation was applied to the patients in the application group with this software. The patients in the control group applied the same rehabilitation program for 6 weeks with a booklet given to them. "Incontinence Impact Questionnaire" and "Urogenital Distress Inventory" to evaluate the severity of incontinence symptoms, "Incontinence Severity Scale" to evaluate urinary incontinence complaint, "3-day bladder diary" to evaluate lower urinary tract symptoms, "Incontinence Quality of Life" for urinary quality of life, "Nottingham Health Profile" to evaluate quality of life, and "Patient Global Recovery Scale" to asses general recovery were applied to all participants at the baseline and at the end of the 6th week. The "System Usability Scale" questionnaire was applied only to the mobile application group to measure the usability of developed mobile application. Result(s): It was concluded that pelvic floor rehabilitation performed with both mobile application and classical method had a significant effect on incontinence severity, urogenital distress, incontinence effect, incontinence quality of life and global patient recovery scores (p<0.05) . When both groups were compared at the end of the treatment, PFMT with mobile application significantly decreased urinary symptoms and increased the quality of life compared to the control group (p<0.05). Conclusion(s): PFMT was performed with the mobile application improved incontinence symptoms and quality of life more than the classical PFMT. The mobile application provides the opportunity to reach more patients, can reduce the costs of treatment, increase the compliance of patients with exercise programs, treat diseases by gaining regular exercise habits and increase the quality of life. This mobile health application that we have developed can be safely recommended as a first-line treatment to SUI patients.

Sönmezer, M., et al. (2023). "Random start ovarian stimulation before gonadotoxic therapies in women with cancer: a systematic review and meta-analysis." Reproductive Biomedicine Online 47(6): 103337.
	The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield. (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Sonntag, B. (2022). "Effects of training intensity on polycystic ovary syndrome markers: a randomized-controlled trial." Gynakologische Endokrinologie 20(3): 210-212.
	
Soohyun, P. and O. Mi-Ra (2022). "Efficacy of dietary supplement on menopausal symptoms in peri- and post-menopausal women: Systematic review and meta-analysis."
	Review question Efficacy of dietary supplement on menopausal symptoms Searches A literature search will be conducted according to each study design (RCTs) using the following search terms: (“menopaus*”) AND (“supplement*” OR “complement*” OR “botanic*” OR “phyto*” OR “herb*”) AND (“placebo” [MeSH]) AND (“clinical Trial” [MeSH] OR “clinical study” OR “RCT” OR “controlled trial” OR “controlled study” OR “human trial” OR “human study”). We will search the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Google Scholar in order to identify relevant trials. Search will be conducted to identify relevant articles published between 2000 and 2022. Types of study to be included All available randomized controlled trials (RCTs) will be included and languages will be limited to English Condition or domain being studied menopausal symptoms Participants/population Inclusion: women with any type of menopausal symptom Exclusion: women using estrogen or hormone therapy Intervention(s), exposure(s) dietary supplement Comparator(s)/control placebo Main outcome(s) - Vasomotor symptoms (hot flushes and night sweats) - Kupperman’s index (KI), menopause rating scale (MRS), and hot flushes Measures of effect weighted mean difference Additional outcome(s) - Kupperman’s index (KI), menopause rating scale (MRS), Greene Climacteric Scale (GCS), Menopause specific quality of life (MENQOL) - Lipids (Cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol) - Hormones (FSH, Estradiol) Measures of effect weighted mean difference Data extraction (selection and coding) Study selection: Two reviewers will independently screen the search results. The first based on title and/or abstract and the second based on full text. Any disagreements will be resolved by consensus. If consensus is not reached, a third reviewer will be consulted to make a decision. Data extraction: Two reviewers will independently extract data using a standardized data extraction format, and inconsistent results will be resolved through confirmation and discussion of the original paper. The following data will be extracted: first author, publication year, study design, participant’s characteristics, types of interventions, and outcomes, etc. Risk of bias (quality) assessment Two reviewers will independently assess the risk of bias in included studies using the Cochran’s Risk of Bias tool. This tool assesses risk of biases in the trials based on random sequence generation, allocation concealment, blinding of the participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Strategy for data synthesis Meta-analysis will be performed using Cochrane software Review Manager 5.4, otherwise descriptive analysis will be performed. Data will be presented by weighted mean difference with its 95% CI for continuous outcomes. I² statistic test will be used to estimate the percentage of heterogeneity between the studies. Meta-analysis will be performed according to a fixed-effects model, but if there are heterogeneity (I²>50%), cause of the heterogeneity will be investigated if possible. In addition, a random effects model will be performed if clinically appropriate. Analysis of subgroups or subsets If necessary, subgroup analyses will be conducted according to 1) type of supplement, 2) menopausal period Contact details for further information Soohyun Park shpark0204@kfri.re.kr Organisational affiliation of the review Korea Food Research Institute Review team members and their organisational affiliations Dr Soohyun Park. Korea Food Research Institute Dr Mi-Ra Oh. Clinical Trial Center for Functional Foods Type and method of review Intervention, Meta-analysis, Systematic review Anticipated or actual start date 01 June 2022 Anticipated completion date 30 June 2023 Funding sources/sponsors Korea Food Research Institute Conflicts of interest Language English Country South Korea Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Dietary Supplements; Female; Humans; Menopause Date of registration in PROSPERO 24 December 2022 Date of first submission 13 December 2022

Soontrapa, N., et al. (2022). "The effectiveness of desogestrel for endometrial protection in women with abnormal uterine bleeding-ovulatory dysfunction: a non-inferiority randomized controlled trial." Scientific Reports 12(1): 1662.
	Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference - 9.1-24.4%, non-inferiority limit of - 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).

Sophia, H. and D. Panagiotis (2024). "Co-enzyme Q10 for improving the reproductive outcomes of poor responders undergoing IVF: a systematic review and meta-analysis."
	Review question Does coenzyme Q10 improve reproductive outcomes of poor responders undergoing IVF? Searches A systematic search of the literature will be performed in different electronic databases (mainly PubMed and Scopus) per PRISMA to identify relevant studies published up to the present date in English. Inclusion criteria will focus on randomized controlled trials examining the adjuvant treatment with coenzyme Q10 in poor responders undergoing IVF. Studies conducted in animals will be excluded. Secondary sources will present other meta-analyses and systematic reviews. Types of study to be included We will include randomized controlled trials to examine the potential beneficial effect of coenzyme Q10 on the reproductive outcomes of poor responders undergoing IVF. Condition or domain being studied Assisted reproductive technology (ART) is on the rise globally and presents a valuable opportunity for infertile couples to have a baby. Poor ovarian response (POR) to ovarian stimulation as part of in vitro fertilization (IVF) presents a major challenge in ART, affecting up to 20%. While oxidative stress seems to have a negative impact on reproductive outcomes, coenzyme Q10, a naturally occurring antioxidant and energizer in the body, is gaining attention as its supplementation is being promoted to treat several medical conditions, including improving the reproductive outcomes of poor responders undergoing IVF. Despite its beneficial effects being emphasized in several studies, it is not FDA-approved yet and needs more research. Participants/population Inclusion criteria: women in their reproductive years with poor ovarian response (using the Bologna and Poseidon criteria) undergoing IVF Exclusion criteria: women not in their reproductive years, without poor ovarian response Intervention(s), exposure(s) Inclusion criteria: oral supplementation of coenzyme Q10 regardless of dosage and duration Exclusion criteria: supplementation of any medication which could potentially interfere with the effects of coenzyme Q10 Comparator(s)/control A control group that only received the COS regimen and no supplementation of coenzyme Q10. Main outcome(s) Primary outcomes: Live birth rates (LBR) and clinical pregnancy rates (CPR)(confirmed gestational sac or fetal heartbeat on U/S) Measures of effect odds ratio Additional outcome(s) Secondary outcomes: miscarriage rates (MR), ovarian response to stimulation parameters (number of mature follicles, oocytes retrieved, fertilization rate, duration of stimulation, total dose of gonadotropins, peak E2 serum level, endometrial thickness on the day of hCG administration) and embryo quality Measures of effect odds ratio Data extraction (selection and coding) One reviewer will initially screen records for inclusion based on predetermined inclusion criteria. This will be done by screening titles and abstracts, followed by full-text assessment for eligibility. A second reviewer will then check decisions independently. Disagreements will be discussed to reach a consensus. Furthermore, two additional reviewers with relevant expertise will be called in. In the same way, data will be extracted. One person will extract data, which include information about study design (RCT’s) and methodology, participants (e.g., age, demographics), definition of POR (e.g., Bologna criteria, Poseidon criteria), co-enzyme Q10 treatment (e.g., dosage, duration), and measures of effect and outcomes (live birth rates (LBR), clinical pregnancy rates (CPR), miscarriage rates (MR), ovarian response to stimulation parameters (number of mature follicles, oocytes retrieved, fertilization rate, duration of stimulation, total dose of gonadotropins, peak E2 serum level, endometrial thickness on the day of hCG administration) and embryo quality). A second person will check the extracted data. Disagreements will be discussed to reach a consensus. Furthermore, two additional reviewers with relevant expertise will be called in. Sensitivity analysis will be done in case of missing data to measure its impact on the results. Data will be recorded in an Excel spreadsheet. Risk of bias (quality) assessment The Risk of bias (quality) assessment will include characteristics such as methods of randomization, treatment allocation, blinding of participants, completeness of outcome data, allocation concealment, and other sources of bias. Initially, one reviewer will explore potential bias using the Cochrane risk of bias tool (RoB 2). A second reviewer will check the results. Disagreements will be discussed to reach a consensus. Furthermore, two additional reviewers with relevant expertise will be called in. Strategy for data synthesis For a meta-analysis at least two studies are needed. For this systematic review, at least three studies reporting similar outcomes are favored for the synthesis of data. The outcomes of interest which will be synthesized include the primary and secondary outcomes defined previously. The odds ratio will be calculated for each outcome based on available data. Heterogeneity among studies will be assessed using the I^2 index. Analysis of subgroups or subsets A subgroup analysis focusing on age as a potential variable influencing the effectiveness of coenzyme Q10 supplementation for improving reproductive outcomes is planned. It is important to assess whether the effectiveness varies across different age groups since, first, age is a well-known factor affecting reproductive outcomes, and second, there is the theory that coenzyme Q10 as an antioxidant may only have an effect on reproductive outcomes in older individuals in which the mitochondrial function is not intact due to oxidative stress. Assessing the effect of coenzyme Q10 within different age groups could provide clinically relevant information and future guidance for personalized treatment strategies. As fertility declines gradually with age and significantly after the age of 35, groups are planned to be divided into participants < 35 years and into participants ≥ 35 years. A logistic regression using individual-level data is planned to control potential confounding factors. Contact details for further information Sophia Hausmann sh191797@students.euc.ac.cy Organisational affiliation of the review European University Cyprus https://euc.ac.cy/en/ Review team members and their organisational affiliations Ms Sophia Hausmann. European University Cyprus Professor Panagiotis Drakopoulos. Centre for Reproductive Medicine (UZ Brussel); European University Cyprus Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 11 February 2024 Anticipated completion date 31 May 2024 Funding sources/sponsors none Conflicts of interest Language English Country Cyprus, Germany, Greece Stage of review Review Ongoing

Sophie, S., et al. (2021). "Antidepressant use during pregnancy and the association with miscarriage and stillbirth: systematic review and meta-analysis."
	Review question Is antidepressant use during pregnancy associated with miscarriage? Is antidepressant use during pregnancy associated with stillbirth? Searches Databases searched include: MEDLINE, EMBASE and PsycINFO, from inception to March 8th 2021. No restrictions will be placed on language, publication date, publication status or methodological differences. All papers included will be peer-reviewed. Search terms will be re-run prior to analysis being conducted to ensure any publications released since 8th March 2021 will be captured. Types of study to be included Observational studies including case-control, cross-sectional and cohort design will be used. Randomised controlled trials will be included; however, we do not anticipate finding any study designs of this type due to the ethical issues of including pregnant women in RCTs. Reviews, meta-analyses, ecological studies, case reports and case series will be excluded. Reviews and meta-analyses will be taken to identify further papers and analyse where gaps in literature exist. Condition or domain being studied Antidepressant use during pregnancy, and the birth outcomes of miscarriage and stillbirth. Participants/population Inclusion: Pregnant women Exclusion: Animal studies will be excluded. Additionally, papers which are solely focusing on individuals with fertility issues or fertility treatment in combination with antidepressant use will be excluded, unless the comparison group also have the same fertility issues. Intervention(s), exposure(s) The exposure will be antidepressant use during pregnancy. We will only be investigating the following types of antidepressants: Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), and norepinephrine and dopamine reuptake inhibitors (NDRIs). There will be no restrictions placed on the exposure regarding type, timing of intake, dose of antidepressant, or duration of use. No exclusions will be made with regard to medication adherence. Studies whereby the exposure is a combination of antidepressants and another drug type (including anxiolytics) will be excluded, as it will then be unclear whether the effects are driven by antidepressants or the other drug type. The studies included should only be focusing on the exposure of antidepressants. However, studies that are investigating more than one drug type but provide effect estimates for each drug type separately will still be included. Additionally, studies involving polypharmacy where they are solely focusing on the effect of antidepressant exposure, but the individuals may also be taking other types of drugs will also be included. Comparator(s)/control We will include studies where the comparison group is either; women taking a different antidepressant to the primary specified type, or women not on antidepressant treatment. Comparisons and controls will also be included for all the antidepressant interventions listed above, as well as their combinations. When the control group involves no antidepressant and no maternal depression, then careful consideration will be applied when investigating confounding by indication. Context Research will be conducted across all range of contexts and countries. Main outcome(s) The two primary outcomes that will be investigated is the presence or absence of either miscarriage or stillbirth. The outcome of miscarriage is defined as the spontaneous loss of foetus before the 20th week of pregnancy. Other terminology for miscarriage includes spontaneous abortion. The outcome of stillbirth is defined as any death of a foetus after 20 weeks of gestation. Other terminology for stillbirth includes fetal death. The studies selected should have either miscarriage, stillbirth or both as one of their outcomes, it does not need to be their specified primary or secondary outcome. Measures of effect The summary effect estimates that will be included in the meta-analysis will be the ORs, HRs or IRRs reported in the study, or calculation of ORs from the raw data supplied in the study. Odds ratio and risk ratio will be treated as equivalent measures due to the low prevalence of miscarriage and stillbirth. Additional outcome(s) None Data extraction (selection and coding) We will carry out medical subject heading (MeSH) terms and keyword searches for antidepressants AND (still birth OR miscarriage). Two researchers will review all titles and abstracts in parallel independently to select studies for inclusion. To reduce the risk of missing potentially relevant studies, a deliberately lenient approach will be adopted for this first level of screening. When multiple papers are found on the same cohort, the paper with the most detail will be taken. Cross-checking then occurred for selected articles to discuss discrepancies. Three authors will complete full text screening and reasons for rejection of articles will be noted. Any discrepancies will be discussed. A fourth reviewer with extensive clinical experience as a psychiatrist will be available to advise on eligibility. The decisions will be illustrated using a PRISMA flow diagram. The software used to carry out study selection will be endnote. We will use the Population, Exposure, Comparator, Outcomes, Study characteristics (PECOS) framework to systematise data extraction. Data will be extracted using a standardised template in Excel containing information on the following five domains: • Population: characteristics of the study population, recruitment and sampling methods, inclusion/exclusion criteria; • Exposure: exposure status definition and identification, number of exposed subjects, any exclusions; • Comparators: identification and definition of unexposed individuals, number of unexposed subjects, any exclusions; • Outcomes: definition and identification of outcomes, number of subjects, any exclusions, length of follow-up; • Study characteristics: study design, authors, publication year, setting/source of participants, period of study, aims. Unadjusted and fully adjusted effect estimates, and confidence intervals will be extracted. Details of confounders will be noted, and results of additional stratified analyses. Two individuals will extract from a study to check extraction process. Then data from remaining studies will be extracted by one reviewer. We will consider contacting corresponding authors to obtain any missing information. Risk of bias (quality) assessment The tool of ROBINS-I will be used to conduct a risk of bias quality assessment on these observational studies. The domains which will be assessed include confounding, selection bias, information bias and reporting bias. Signalling questions within the tool will aid the judgement and scoring in each of the bias domains. Then each paper will have an overall risk of bias judgement and its direction. Funnel plot may be utilised to assess presence of publication bias, however reporting bias is likely to act differently in varying study designs. This would then produce asymmetry that would be driven by heterogeneity, rather than small-study effects. Therefore, studies will be grouped according to study design and then assessed for publication bias (eg within a funnel plot the dots for each study will be coloured according to their study design.) Two reviewers will complete risk of bias assessment on one study, after ensuring assessment is in line with expectations one sole reviewer will then assess the remaining studies. The results of this section will inform data synthesis whereby any studies highlighted as having a very high risk of bias (pre-set threshold) will be excluded when conducting the sensitivity analysis. Strategy for data synthesis We will conduct a narrative synthesis in which studies are grouped by outcome and exposure definitions. The programme STATA will be used for data synthesis. Due to the varying antidepressant types, dosage, duration and timing of use there will be heterogeneity between the studies, assessed using the I² statistic. Therefore, a random effects meta-analysis will be conducted producing an average exposure effect. The summary effect estimates that will be included in the meta-analysis will be the ORs, HRs or IRRs reported in the study, or calculation of ORs from the raw data supplied in the study. An overall meta-analysis will be produced. However, separate meta-analyses/meta-regression may also be utilised for the varying study designs as these designs will carry varying levels of bias which could lead to large amount of heterogeneity, and the combination of all study designs in one meta-analysis not providing much insight. These separate analyses will be dependent on the number and type of studies identified. Depending on the number and type of studies identified, a network meta-analysis may be conducted which compares different types of antidepressants. This could also aid when comparing between different indications for antidepressant. Sensitivity analysis whereby the papers with less credibility as defined by ROBINS-I tool will be removed and investigation of whether this produces any impact on the summary effect. Depending on the number and type of studies identified, a meta-regression will be conducted to investigate the effect on summary estimates when clustering the same study designs and comparing between. Depending on the number and type of studies identified, a meta-regression will be conducted to investigate average exposure times of antidepressant for each study and corresponding effect estimates. Analysis of subgroups or subsets Depending on whether enough suitable studies are identified, studies will be grouped according to timing of antidepressant exposure to minimise the differential effects seen which will be driven by differential time points of exposure. Depending on whether enough suitable studies are identified, studies will be grouped according to their level of confounding adjustment for maternal depression. This would mean studies could be accurately compared dependent on whether confounding by indication had been accounted for. Depending on whether enough suitable studies are identified, subgroups that will also be investigated include the type of antidepressant used. Investigating the effect estimates within each antidepressant type could reveal patterns and associations that would otherwise not be seen if subgroups aren’t utilised. Certain antidepressants could be found to have higher effect estimates than other; therefore, this subgroup analysis would be very influential for clinical practice policy. Subgroups of dosage of antidepressant will also be investigated if there are enough available studies. Contact details for further information Dr Harriet Forbes Harriet.forbes@bristol.ac.uk Organisational affiliation of the review Centre for Academic Mental Health, University of Bristol, UK Review team members and their organisational affiliations Miss Sophie Smith. University of Bristol Miss Florence Martin. University of Bristol Dr Dheeraj Rai. University of Bristol Dr Harriet Forbes. University of Bristol Type and method of review Epidemiologic, Meta-analysis, Narrative synthesis, Network meta-analysis, Systematic review Anticipated or actual start date 08 March 2021 Anticipated completion date 03 January 2022 Funding sources/sponsors National Institute for Health Research Wellcome Trust Grant number(s) State the funder, grant or award number and the date of award NIHR Predoctoral Fellow NIHR301119 - Date of award: 10/2020 Wellcome Trust PhD Studentship WT 218495/Z/19/Z - Date of award: 09/2020 Conflicts of interest Language English Country England Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Abortion, Spontaneous; Antidepressive Agents; Female; Humans; Pregnancy; Risk Factors; Stillbirth Date of registration in PROSPERO 25 June 2021 Date of first submission 24 June 2021 Stage of review at time of this submission

Sophie, S., et al. (2023). "The effects on mental health of hormonal or hormonal blocking treatments in women with endometriosis."
	Review question [1 change] The effects on mental health of hormonal or hormonal blocking treatments in women with endometriosis Population - Women with endometriosis Intervention - Hormonal treatment / hormonal-blocking treatment Comparison - Non hormonal treatment, hormonal/anti-hormonal treatment other than the intervention, waiting list controls and placebo Outcomes - Impact on mental health Studies included - Randomised control trials, non-randomised controlled trials, observational studies with comparison, case series where n is greater than or equal to 5. Searches [1 change] OVID to include: Journals@Ovid Full text, AMED (Allied and Complementary Medicine), Embase, Ovid Emcare, Ovid MEDLINE(R) ALL Separate identical searches performed on: Web of Science, PsycINFO, CINAHL, Cochrane Central Search will be from inception of databases to present date There will be no language restrictions Searches will be re-run prior to the final analysis Grey literature will be included following the SIGLE classification; Conference abstracts will be excluded. Types of study to be included Randomised control trials, non-randomised control trials, observational studies Condition or domain being studied Women with endometriosis Participants/population Inclusion: women with endometriosis (all ages) Intervention(s), exposure(s) Hormonal treatment / hormonal-blocking treatment Comparator(s)/control Non hormonal treatment (placebo or surgery alone) vs. hormonal/anti-hormonal treatment Main outcome(s) Assess the effects of hormonal and hormonal-blocking treatments on mental health in women with endometriosis Mental health measured by established disease-specific assessment tools relevant to mental health; Beck Depression Inventory [BDI] Hospital Anxiety and Depression Scale (HADS) State-Trait Anxiety Inventory [STAI] General Health Questionnaire Eysenck Personality Questionnaire [EPQ] The Golombok Rust Inventory of Marital State Golombok Rust Inventory of Sexual Satisfaction (GRISS) The Short-Form McGill Pain Questionnaire Symptom Checklist-90-R Symptom Checklist-90-Revised (SCL-90-R) State-Trait Anger Expression Inventory-2 Self-Rating Anxiety Scale Self-Rating Depression Scale Quality of Life Index Hamilton Rating Scale for Depression (HAM-D) Hamilton Rating Scale for Anxiety (HAM-A) Spielberger STAI World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF) Status of health questionnaire (SF-36) Hospital Anxiety and Depression Scale-German Version (HADS-D) Endometriosis Health Profile (EHP-30) The Dutch version of the Female Sexual Function Index (FSFI) Short Form-12 (SF-12) Pain Catastrophizing Scale (PCS) Sexual Self-Consciousness Scale (SSCS) Toronto Alexithymia Scale (TAS-20) Pain Disability Index (PDI) Chronic Pain Questionnaire (CPQ) Coping Styles Questionnaire (CSQ) Courtauld Emotional Control Scale (CECS) Where quality of life scales reviewed, only the Emotional-wellbeing domain included for analysis Measures of effect Risk difference, odds ratios, standardised mean differences Additional outcome(s) Suicidal ideation irreversible negative mental health effects Depressive episodes Anxiety Bipolar affective disorder Mania Manic episodes Suicidal ideation Suicidal attempt Suicide Mental health decline Panic attacks Panic disorders Mood disorder Psychosis Psychotic episodes Psychological side effects Psychological harm Psychiatric conditions Measures of effect As above Data extraction (selection and coding) Study selection - Two reviewers applying eligibility criteria and selecting studies for inclusion in the systematic review independently screen: Studies selected will be on the basis of abstract level and full text level by two people - Disagreements between individual judgements will be resolved by a senior reviewer - The software system or mechanism for recording decisions: COVIDENCE Data extraction: - Psychological outcome parameters for women with endometriosis will be extracted and tabulated - We will also include information about study design and methodology, participant demographics and baseline characteristics, numbers of events or measures of effect (where applicable). - Two people will be extracting and checking received data: one will extract data and an other person check the extracted data - Disagreements between individual judgements will be resolved by a senior reviewer - Missing data will be handled by contacting the study investigators for unreported data or additional details. - Data will be reported using COVIDENCE / Excel spreadsheet. Meta-analysis where applicable will be done with RevMan Risk of bias (quality) assessment Qualities of RCT studies will be assessed using criteria set by The York Centre for reviews and dissemination focusing on randomisation, allocation concealment, presence of blinding, explanation of withdrawals and presence or absence of interion to treat analysis Observational studies: Quality assessment will be done using the Newcastle Ottowa scale to grade studies as high, moderate and low risk of bias Disagreements between reviewers will be resolved by discussion and adjudication by a third experienced reviewer. Strategy for data synthesis We will tabulate the characteristics and results of all the included studies; analysis will be quantitative. Where standard errors or ranges are provided, standard deviations will be calculated using standard formulae. Review Manager (version 5.2, The Cochrane Library) will be used for meta-analyses. We will use random effects models because of heterogeneity of participants and interventions. Where outcomes are for continuous measures will use standardised mean differences (SMD) where the outcomes have differing measurement scales. Risk of publication bias will be assessed using funnel plots. If it is not possible to carry out a quantitative analysis we will provide a narrative report. Analysis of subgroups or subsets People who received add back hormonal replacement on hormone blockers Women with pre-existing mental health conditions Contact details for further information Sophie Michelle Strong sophiestrong@nhs.net Organisational affiliation of the review Royal London Hospital Review team members and their organisational affiliations Dr Sophie Strong. Royal London Hospital Miss Krupa Madhvani. Royal London Hospital Miss Elizabeth Ball. Royal London Hospital / City University London Type and method of review Meta-analysis, Synthesis of qualitative studies, Systematic review Anticipated or actual start date 12 October 2022 Anticipated completion date 12 October 2023 Funding sources/sponsors None declared Grant number(s) State the funder, grant or award number and the date of award Not applicable Conflicts of interest There are no conflicts of interest None known Language English Country England Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Counseling; Danazol; Endometriosis; Female; Humans; Pelvic Pain; Waiting Lists Date of registration in PROSPERO 25 January 2023 Date of first submission 18 January 2023

Sorrenti, S., et al. (2023). "Pregnancy and perinatal outcomes of early vs late selective termination in dichorionic twin pregnancy: systematic review and meta-analysis." Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 61(5): 552-558.
	Objective: To evaluate outcomes of dichorionic twin pregnancies undergoing early vs late selective termination of pregnancy (ST).; Methods: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to March 2022. The primary outcome of this study was pregnancy loss prior to 24 weeks' gestation. The secondary outcomes included preterm birth (PTB) before 37, 34, and 32 weeks, preterm prelabor rupture of membranes (PPROM), gestational age (GA) at delivery, Cesarean delivery, mean birth weight, 5-min Apgar score < 7, overall neonatal morbidity and neonatal survival. Only prospective or retrospective studies reporting data on the outcome of early (before 18 weeks) vs late (at or after 18 weeks) ST in dichorionic twin pregnancies were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale for cohort studies. Random-effects head-to-head meta-analysis was used to analyze the data.; Results: Seven studies reporting on 649 dichorionic twin pregnancies were included in this systematic review. The risk of pregnancy loss prior to 24 weeks was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST (1% vs 8%; odds ratio (OR), 0.25 (95% CI, 0.10-0.65); P = 0.004). The risk of PTB was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST when considering PTB before 37 weeks (19% vs 45%; OR, 0.36 (95% CI, 0.23-0.57); P < 0.00001), before 34 weeks (4% vs 19%; OR, 0.24 (95% CI, 0.11-0.54); P = 0.0005) and before 32 weeks (4% vs 20%; OR, 0.21 (95% CI, 0.05-0.85); P = 0.03). The mean birth weight was significantly greater in the early-ST group (mean difference (MD), 392.2 g (95% CI, 59.1-726.7 g); P = 0.02), as was the mean GA at delivery (MD, 2.47 weeks (95% CI, 0.04-4.91 weeks); P = 0.049). There was no significant difference between dichorionic twin pregnancies undergoing early compared with late ST in terms of PPROM (P = 0.27), Cesarean delivery (P = 0.38), 5-min Apgar score < 7 (P = 0.35) and neonatal survival of the non-reduced twin (P = 0.54).; Conclusions: The risk of pregnancy loss prior to 24 weeks and the rate of PTB before 37, 34 and 32 weeks were significantly higher in dichorionic twin pregnancies undergoing late vs early ST, thus highlighting the importance of early diagnosis of fetal anomalies in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Sothornwit, J., et al. (2022). "Immediate versus delayed postabortal insertion of contraceptive implant." The Cochrane Database of Systematic Reviews 5: CD013565.
	Background: Contraceptive implants are one of the most effective contraceptive methods, providing a long duration of pregnancy protection and a high safety profile. Hence this method is suitable for optimizing the interpregnancy interval, especially for women undergoing abortion. Women who have had abortions are at high risk of rapid repeat pregnancies. Provision of effective contraception at the time of an abortion visit can be a key strategy to increase access and uptake of contraception. A review of the evidence was needed to evaluate progestin-releasing implants for immediate use at the time of abortion, including whether immediate placement impacts the effectiveness of medical abortion, which relies on antiprogestogens.; Objectives: To compare contraceptive implant initiation rates, contraceptive effectiveness, and adverse outcomes associated with immediate versus delayed insertion of contraceptive implants following abortion.; Search Methods: We searched for all relevant studies regardless of language or publication status up to September 2019, with an update search in March 2021. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Ovid EBM Reviews), MEDLINE ALL (Ovid), Embase.com, CINAHL (EBSCOhost) (Cumulative Index to Nursing and Allied Health Literature), Global Health (Ovid), LILACS (Latin American and Caribbean Health Science Information database), Scopus, ClinicalTrials.gov, and the WHO ICTRP. We examined the reference lists of pertinent articles to identify other studies.; Selection Criteria: We sought randomized controlled trials (RCTs) comparing immediate versus delayed insertion of contraceptive implant for contraception following abortion.; Data Collection and Analysis: We followed the standard procedures recommended by Cochrane. To identify potentially relevant studies, two review authors (JS, LS) independently screened the titles, abstracts, and full texts of the search results, assessed trials for risk of bias, and extracted data. We computed the risk ratio (RR) with 95% confidence intervals (CIs) for binary outcomes, and the mean difference (MD) with 95% CIs for continuous variables.; Main Results: We found three RCTs including a total of 1162 women. Our GRADE assessment of the overall certainty of the evidence ranged from moderate to very low, downgraded for risk of bias, inconsistency, and imprecision. Utilization rate at six months may be slightly higher for immediate compared with delayed insertion (RR 1.10, 95% CI 1.05 to 1.15; 3 RCTs; 1103 women; I 2 = 62%; low certainty evidence). Unintended pregnancy within six months after abortion was probably lower with immediate insertion compared with delayed insertion (RR 0.25, 95% CI 0.08 to 0.77; 3 RCTs; 1029 women; I 2 = 0%; moderate certainty evidence). Immediate insertion of contraceptive implants probably improves the initiation rate compared to delayed insertion following medical abortion (RR 1.26 for medical abortion, 95% CI 1.21 to 1.32; 2 RCTs; 1014 women; I 2 = 89%; moderate certainty evidence) and may also improve initiation following surgical abortion (RR 2.32 for surgical abortion, 95% CI 1.79 to 3.01; 1 RCT; 148 women; I 2 = not applicable; low certainty evidence). We did not pool results for the implant initiation outcome over both abortion types because of very high statistical heterogeneity. For medical termination of pregnancy, we found there is probably little or no difference between immediate and delayed insertion in overall failure of medical abortion (RR 1.18, 95% CI 0.58 to 2.40; 2 RCTs; 1001 women; I 2 = 68%;moderate certainty evidence). There may be no difference between immediate and delayed insertion on rates of abnormal bleeding at one month after abortion (RR 1.00, 95% CI 0.88 to 1.14; 1 RCT; 462 women; I 2 = not applicable; low certainty evidence).; Authors' Conclusions: Provision of progestin-releasing implants concurrently with abortifacient agents likely has little or no negative impact on overall failure rate of medical abortion. Immediate insertion probably improves the initiation rate of contraceptive implant, as well as unintended pregnancy rate within six months after abortion, compared to delayed insertion. There may be no difference between immediate and delayed insertion approaches in bleeding adverse effects at one month after abortion. (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

South, E. C., et al. (2021). "Nurtured in Nature: a Pilot Randomized Controlled Trial to Increase Time in Greenspace among Urban-Dwelling Postpartum Women." Journal of urban health : bulletin of the New York Academy of Medicine 98(6): 822-831.
	Spending time in nature is associated with numerous mental health benefits, including reduced depression and improved well-being. However, few studies examine the most effective ways to nudge people to spend more time outside. Furthermore, the impact of spending time in nature has not been previously studied as a postpartum depression (PPD) prevention strategy. To fill these gaps, we developed and pilot tested Nurtured in Nature, a 4-week intervention leveraging a behavioral economics framework, and included a Nature Coach, digital nudges, and personalized goal feedback. We conducted a randomized controlled trial among postpartum women (n = 36) in Philadelphia, PA between 9/9/2019 and 3/27/2020. Nature visit frequency and duration was determined using GPS data. PPD was measured using the Edinburgh Postnatal Depression Scale (EPDS). Participants were from low-income, majority Black neighborhoods. Compared to control, the intervention arm had a strong trend toward longer duration and higher frequency of nature visits (IRR 2.6, 95%CI 0.96-2.75, p = 0.059). When analyzing women who completed the intervention (13 of 17 subjects), the intervention was associated with three times higher nature visits compared to control (IRR 3.1, 95%CI 1.16-3.14, p = 0.025). No significant differences were found in the EPDS scores, although we may have been limited by the study's sample size. Nurture in Nature increased the amount of time postpartum women spent in nature, and may be a useful population health tool to leverage the health benefits of nature in majority Black, low-resourced communities.

Spagnolo, E., et al. (2022). "Role of fluorescence imaging for intraoperative intestinal assessment in gynecological surgery: a systematic review." Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 31(7): 992-999.
	Background: Our aim was to review the current knowledge of the role of fluorescence imaging for intraoperative intestinal assessment in gynecological surgery.; Material and Methods: A computer-based systematic review was performed from 2000 to 2020. All articles describing the use of indocyanine green (ICG) applied to bowel assessments in gynecology or endometriosis surgery were considered for review.; Results: ICG is an effective tool for assessing bowel vascularization, potentially preventing anastomotic leakage and recto-vaginal fistula and can therefore be useful for endometriosis surgery or bowel assessment in gynecological oncology procedures. Real-time characterization of the hypovascular pattern of endometriotic nodules has been associated with a larger nodule size and lower microvessel density, helping surgeons choose the best transecting line and the most appropriate technique. ICG angiography allows for a laparoscopic and intrarectal bowel assessment, which can act as a double check of bowel perfusion, enabling the assessment of mucosa vascularization. ICG fluorescence can guide intraoperative decision-making after intestinal anastomosis, discoid resection, and rectal shaving, preventing anastomotic leakage and postoperative recto-vaginal fistula in low anterior resections.; Conclusions: ICG angiography provides a better intestinal assessment. Larger, prospective, randomized controlled studies are needed to validate the technique and confirm these encouraging results.

Sparic, R., et al. (2024). "Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice." Hormones 23(1): 49-58.
	Purpose: Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. Method(s): A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. Result(s): Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. Conclusion(s): The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women. Copyright © The Author(s), under exclusive licence to Hellenic Endocrine Society 2023.

Speer, L. (2023). "Letrozole More Effective Than Clomiphene for Infertility Treatment Among Individuals With Polycystic Ovary Syndrome." American family physician 108(2): 203-204.
	
Spence, R. (2022). "The ECHO trial - Exercise during chemotherapy for ovarian cancer." Asia-Pacific Journal of Clinical Oncology 18(Supplement 3): 114.
	Higher levels of physical activity pre- and post-diagnosis of cancer have been associated with improved survival post-cancer. However, evidence to date does not demonstrate cause and effect. Consequently, trial evidence is now needed to demonstrate the effect of exercise on survival in a clinical setting. The Exercise during Chemotherapy for Ovarian cancer (ECHO) trial is a phase III, randomized, controlled trial, designed to determine the effect of exercise on progression-free survival and physical wellbeing for patients receiving first-line chemotherapy for ovarian cancer. Women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy are eligible to participate in ECHO (target sample size; n = 500). Following consent, women are randomly allocated (1:1), with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant versus adjuvant) to either the Exercise Intervention (plus Usual Care) or Usual Care alone. The exercise intervention involves individualized exercise prescription with a weekly target of 450 metabolic equivalent minutes per week (i.e., at least 150 min of moderate-intensity, mixed-mode exercise), delivered to participants via weekly telephone sessions with a trial-trained exercise professional for the duration of first-line chemotherapy. Outcomes of interest include progression-free survival and physical wellbeing (primary outcomes), and overall survival, physical function, body composition, quality-of-life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage. Throughout this presentation, the rationale supporting the study design and characteristics will be provided and preliminary findings related to exercise safety and feasibility will be described. The target sample size will be met by December 2022, and results related to the primary and secondary research questions will become available within the next few years.

Spira, A. I., et al. (2022). "Phase I study of HFB200301, a first-in-class TNFR2 agonist monoclonal antibody in patients with solid tumors selected via Drug Intelligent Science (DIS)." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Tumor necrosis factor receptor-2 (TNFR2) is expressed on effector CD8+ T cells, CD4+ T cells, T regulatory cells, natural killer cells, and myeloid cells. Targeting TNFR2 is anticipated to yield effective anti-tumor immunity by stimulating T-cell and NK-cell activation and proliferation in the tumor microenvironment. HFB200301 is a first-in-class anti-TNFR2 agonistic monoclonal antibody that triggers both innate and adaptive immune stimulation by binding to a specific epitope on TNFR2. HFB200301 has demonstrated dose-dependent anti-tumor activity in human TNFR2 knock-in mice bearing MC38 and Hepa1-6 syngeneic tumors. Method(s): HFB200301 is being evaluated in a first-inhuman, open-label, multi-center, dose escalation and expansion study in adult patients with advanced solid tumors. A single-cell immune profiling platform, DIS, was deployed to identify unique tumor-infiltrating T cell signatures that could help optimize patient selection for HFB200301 treatment. It is hypothesized that the presence of an effector T cell subpopulation that express both TNFR2 and CD8A in solid tumors may represent a tumor microenvironment favorable to TNFR2 agonism. The following cancer indications have been identified based on the prevalence of a TNFR2 high/CD8 high signature: Epstein-Barr Virus positive (EBV+) gastric cancer, clear cell renal cell carcinoma (ccRCC), cutaneous melanoma, testicular germ cell tumor (TGCT), soft tissue sarcoma (STS), and PD-L1+ cancers: cervical cancer, pleural mesothelioma, lung adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC). The escalation portion of the study explores increasing doses in cohorts of up to six patients, utilizing mTPI-2 design to determine recommended dose(s) for expansion (RDE(s)). Based on pharmacokinetic modeling to maximize HFB200301 activity, 60-minute intravenous infusions of HFB200301 are administered every 4 weeks. Once RDE(s) is determined, expansion into three indication- specific cohorts is planned to determine the recommended phase 2 dose (RP2D). Key eligibility criteria include histologically documented advanced or metastatic solid tumors in the above listed indications. Patient enrollment opened in February 2022 in the USA, with plans for additional clinical sites in Spain and China. The primary objective is to identify the RDE, characterize safety and tolerability of HFB200301, and determine RP2D. Secondary objectives include pharmacokinetic parameters, preliminary evidence of anti-tumor efficacy (e.g., ORR, DCR, DOR) and pharmacodynamic evaluation (e.g., T cell subsets) in the blood and in the tumor. Furthermore, a potential predictive biomarker signature derived based on the DIS single-cell immune profiling approach will be investigated retrospectively.

Spruijt Melle, A., et al. (2022). "The efficacy of botulinum toxin a injections in pelvic floor muscles in chronic pelvic pain patients: a systematic review and meta-analysis." International Urogynecology Journal 33(11): 2951-2961.
	Introduction and Hypothesis: Chronic pelvic pain (CPP) is a common multifactorial condition affecting 6 to 27% of women aged 18-50 years worldwide. This study was conducted to review and meta-analyse the current literature on the reduction of chronic pelvic pain after botulinum toxin A (BTA) injection.; Method: In July 2021 we performed a systematic search in PubMed and EMBASE to assess the benefits of BTA injection in pelvic floor muscles in women with chronic pelvic pain. Primary outcome was reduction in visual analogue scale (VAS) after treatment. Secondary outcomes evaluated were: reduction of dyspareunia, pelvic floor resting pressure and quality of life. Identified reports were assessed on quality of reporting and risk of bias. Standardized mean difference (SMD) was used to combine and analyse outcomes of the included studies.; Results: Eight studies with 289 participants were considered eligible to be included in this systematic review and meta-analysis. After recalculating SMD into VAS scores (0-100), long-term follow-up (24-26 weeks) showed a significant 15-point improvement in VAS scores (95% CI: 8.8-21.5) for non-menstrual pelvic pain and a 13-point improvement (95% CI: 2.1-24.0) for dyspareunia. BTA injection had a significant effect on pelvic floor resting pressure and quality of life.; Conclusion: There is limited scientific evidence on the effectiveness of BTA injections in pelvic floor muscles in women with chronic pelvic pain. The available studies show that BTA injections significantly reduce pain levels and improve quality of life at 6 months follow-up.; Prospero Id: CRD42018105204. (© 2022. The Author(s).)

Spyropoulou, K., et al. (2020). "Myomectomy during pregnancy: A systematic review." European Journal of Obstetrics, Gynecology, and Reproductive Biology 254: 15-24.
	Objective: Uterine fibroids affect 2-10 % of pregnant women. Although usually asymptomatic, they may be associated with pregnancy complications. Myomectomy is preferably avoided antenatally, however, it has been reported in symptomatic cases that did not respond to conservative management. The aim of this study was to summarize the published literature and present the reported outcomes and associated risks of this procedure.; Study Design: A systematic research of the literature was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library, including case reports and case series. An effort was made to numerically analyse all parameters included in the case reports.; Results: Overall, 54 relevant articles were identified, including 97 patients. The median gestational age at diagnosis was 13 (range 6-26) weeks, while the median age at myomectomy was 16 (range 6-26) weeks. Abdominal pain, not responding to medical treatment was the most common indication for surgery. The median number of fibroids removed per patient was one (range 1-5). Most of them were subserous pedunculated or subserous and fundal. Laparotomy (78.4 %) was the principal surgical approach, however, laparoscopic and vaginal operations were also reported. The median duration of surgery was 53 (range 20-150) min. The histopathology revealed necrosis and degeneration as the main findings of removed fibroids. The pregnancy outcome was favourable in most of the cases, with few complications reported.; Conclusion: Based on the limited published data, myomectomy during pregnancy appears as a safe procedure in cases of symptomatic uterine fibroids not responding to conservative management and therefore it may be considered, following appropriate counselling regarding the associated risks.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Squibb, B.-M. (2021). A Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors.
	No Results Available Drug: BMS-986340|Drug: BMS-936558-01|Drug: Docetaxel Incidence of adverse events (AEs)|Incidence of serious adverse events (SAEs)|Incidence of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria|Incidence of AEs leading to discontinuation|Incidence of AEs leading to death|Pharmacokinetic (PK) parameters of BMS-986340 administered as monotherapy: Maximum concentration (Cmax)|PK parameters of BMS-986340 administered as monotherapy: Time to maximum concentration (Tmax)|PK parameters of BMS-986340 administered as monotherapy: Area under the concentration-time curve 1 dosing interval (AUC (TAU))|PK parameters of BMS-986340 administered as monotherapy: Observed concentration at the end of the dosing interval (Ctau)|PK parameters of BMS-986340 administered in combination with nivolumab: Maximum concentration (Cmax)|PK parameters of BMS-986340 administered in combination with docetaxel: Cmax|PK parameters of BMS-986340 administered in combination with nivolumab: Time to maximum concentration (Tmax)|PK parameters of BMS-986340 administered in combination with docetaxel: Tmax|PK parameters of BMS-986340 administered in combination with nivolumab: Area under the concentration-time curve in 1 dosing interval (AUC(TAU))|PK parameters of BMS-986340 administered in combination with docetaxel: AUC(TAU)|PK parameters of BMS-986340 administered in combination with nivolumab: Observed concentration at the end of the dosing interval (Ctau)|PK parameters of BMS-986340 administered in combination with docetaxel: Ctau|Incidence of anti-drug antibodies to BMS- 986340 when administered as monotherapy|Incidence of anti-drug antibodies to BMS- 986340 when administered in combination with nivolumab|Incidence of anti-drug antibodies to BMS- 986340 when administered in combination with docetaxel|Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator|Disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator|Duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator|Progression-free survival rate (PFSR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator All Phase 1|Phase 2 665 Industry Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CA052-002|2021-001188-26|U1111-1265-4508 September 15, 2026

Squibb, B.-M. and E. Inc (2023). A Study of MORAb-202 Versus Investigator's Choice Chemotherapy in Female Participants With Platinum-resistant High-grade Serous (HGS) Ovarian, Primary Peritoneal, or Fallopian Tube Cancer.
	No Results Available Drug: MORAb-202|Drug: Paclitaxel|Drug: Pegylated Liposomal Doxorubicin (PLD)|Drug: Topotecan Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment|Proportion of participants with treatment related adverse events (TRAEs) leading to study discontinuation|Number of participants with adverse events (AEs)|Number of participants with serious adverse events (SAEs)|Number of participants with AEs leading to discontinuation|Number of participants with TRAEs|Number of participants with TRSAEs|Number of participants with AEs of special interest (AESIs)|Number of deaths|Number of participants with laboratory abnormalities|Disease control rate (DCR) by RECIST v1.1 per investigator assessment|Duration of Response (DoR) by RECIST v1.1 per investigator assessment|Progression-free survival (PFS) by RECIST v1.1 per investigator assessment Female Phase 2 90 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment CA116-001|2021-004807-42 October 11, 2026

Srinivas, N., et al. (2023). "ZURANOLONE, A NOVEL GABAA POSITIVE ALLOSTERIC MODULATOR, DOES NOT PROLONG THE QT INTERVAL." Clinical Pharmacology and Therapeutics 113(Supplement 1): S72-S73.
	BACKGROUND: Zuranolone (ZRN) is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid in development as an oral, once-daily, 14-day treatment course for adults with major depressive disorder and postpartum depression. This study evaluated ZRN effects on cardiac repolarization, as assessed by Fridericia-corrected QT interval (QTcF). METHOD(S): This was a double-blind, double-dummy, placebo-and active-controlled, parallel-group study in healthy adults. In Group 1 (n = 32), participants received placebo on day (D) 1 and D9, ZRN 50 mg (therapeutic dose) on D2-7, and ZRN 100 mg (supratherapeutic dose) on D8. In Group 2 (n = 32), participants received placebo D1-9 and moxifloxacin 400 mg/placebo for moxifloxacin on D2 or D9 in a crossover manner. Time-matched serial PK and ECG measurements were QTcF (DELTAQTcF), by concentration-QTc (C-QTc) modeling. RESULT(S): The moxifloxacin C-QTc analysis confirmed assay sensitivity. For ZRN, the slope of the C-QTc model was shallow (0.024 ms per ng/mL). At ZRN Cmax of 98.3 ng/mL (50 mg) and 132.8 ng/mL (100 mg), the predicted placebo-corrected DELTAQTcF estimate (ms; 90% confidence interval [CI]) was -0.31 (-4.71, 4.10) and 0.52 (-4.10, 5.13), respectively. The upper bound of the 90% CI remained <10 ms across the concentration range. ZRN had no QTc effect in the by-timepoint analysis and no effect on heart rate or PR and QRS intervals. Categorical analysis showed no pertinent findings. Most adverse events (95.3%) were mild/ moderate. ZRN PK was as expected with observed concentrations covering the anticipated high clinical use scenario. CONCLUSION(S): ZRN had no clinically relevant effect on cardiac repolarization at therapeutic and supratherapeutic doses.

Srinivasan, D. and F. Lofton Holly (2022). "Effect of GLP-1 agonists on weight loss in patients with polycystic ovary syndrome and obesity: A single-center study." Obesity Pillars (Online) 2: 100016.
	Background: Weight loss of >5% in patients with polycystic ovary syndrome and obesity (PCOS-O) is believed to improve underlying drivers of the syndrome. Weight loss facilitated by GLP-1 agonists in patients with PCOS-O is not well characterized. In this single-center retrospective study, we determined weight loss in patients with PCOS-O with GLP-1 monotherapy versus metformin.; Methods: In this brief report, electronic records of 183 adult patients with PCOS-O were reviewed between January 2020 and April 2021. We identified 12 and 19 patients that were treated with metformin and GLP-1 monotherapy respectively. One patient in each cohort had diabetes mellitus. Weights were reviewed at baseline (prior to therapy initiation) and at six-month follow-up. We analyzed change in weight from baseline and proportion with >5% and 10% weight loss using Fisher exact t -test and chi-square test. Univariate linear regression was used to identify correlations between treatment and weight loss.; Results: Baseline characteristics were similar between metformin (n = 12) and GLP-1 (n = 19) cohorts with the exception of mean days on medication. Following six months of treatment, mean weight loss was 4.9 kg (4.8%) and 9.1 kg (9.8%) in the metformin and GLP-1 cohorts (p = 0.13) respectively. Similar trends were seen in BMI with reductions of 1.8 kg/m 2 (4.7%) and 3.5 kg/m 2 (9.7%). A significantly greater proportion of patients achieved 5% and 10% weight loss with GLP-1 treatment (84.2% and 57.8%, p = 0.01 and p = 0.02) compared to metformin. Univariate linear regression analysis demonstrated a trend towards greater weight loss in patients treated with GLP-1 monotherapy (Coeff: 4.15, 95% CI: 1.3-9.7, p = 0.13) versus metformin.; Conclusion: Our study shows improvements in weight with GLP-1 monotherapy versus metformin as demonstrated by overall weight loss and proportion of patients achieving >5% weight loss. Further prospective randomized controlled studies are needed to establish GLP-1 weight loss efficacy in patients with PCOS-O and clinically related outcomes.; Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Holly Lofton reports a relationship with Eli Lilly and Company that includes: funding grants. Holly Lofton reports a relationship with Novo Nordisk Inc that includes: consulting or advisory and funding grants. (© 2022 The Authors.)

Srinivasan, S., et al. (2024). "Vaginal Metronidazole Activity and Clinical Outcomes for Bacterial Vaginosis." Sexually Transmitted Diseases 51(1 Supplement 1): S422-S423.
	Background: Bacterial vaginosis (BV) recurrence rates may be attributed to factors including poor adherence to antibiotic therapy, inadequate dosing to eradicate BV-associated bacteria (BVAB) or antibiotic resistance. No published studies have linked vaginal concentrations of metronidazole to concentrations of indicator BVAB and BV outcomes. Method(s): Participants with Amsel-BV were prescribed with intravaginal/oral metronidazole and returned after 6-15 days to determine if treatment was effective (test-of-cure) and 16-35 days to evaluate short-term BV recurrence. An antimicrobial assay was developed to assess vaginal metronidazole activity. Anaerobic vaginal bacteria were streaked on Brucella plates and bactericidal activity (clearance zone) of vaginal swab supernatants was used to indicate metronidazole use. Clearance noted on any prescribed days of intravaginal or oral metronidazole was considered any-documented-use while no clearance on any prescribed days was classified as no-documented-use. BVAB2 and Megasphaera spp. concentrations were measured using quantitative PCR (qPCR). Result(s): Of 150 BV episodes in 88 participants, 98 (65.3%) had a test-of-cure visit; any-documented-use of metronidazole was noted in 78 (79.6%) and no-documented-use in 20 (20.4%) episodes. At test-of-cure visits, Amsel-BV was observed in 4/78 episodes (5.1%) among those with any-documented-use of metronidazole and 3/20 episodes (15%) among those with no-documented-use (p=0.15). Of 150 episodes, there was a follow-up visit (16-35 days) for 124 episodes (82.7%); any-documented-use was observed in 82 (66.1%) and no-documented-use in 42 (33.9%) episodes. At this follow-up, Amsel-BV was noted in 21/82 episodes (25.6%) among those with any-documented-use and 18/42 episodes (42.9%) among those with no-documented-use (p=0.041). We compared changes in BVAB concentrations in 150 episodes with daily qPCR data for 10 days post-initiation of antibiotics. Among those with any-documented-use, there was a decrease of 0.26 log 16S rRNA copies/swab of BVAB2 each day versus 0.13 log copies/swab in the no-documented-use group (difference in slope=0.13, p< 0.001). Likewise, there was a decrease in 0.34 log copies/swab of Megasphaera spp. in the group with any-documented-use compared to 0.13 log copies in the no-documented-use group (difference in slope=0.21, p< 0.001). Conclusion(s): A substantial fraction of participants lack evidence of use of metronidazole as indicated by our bioassay, leading to ineffective clearance of BVABs which may result in short-term BV recurrence.

Srinivasaraghavan, N., et al. (2022). "Effect of Whey Protein Supplementation on Perioperative Outcomes in Patients with Cancer-A Systematic Review and Meta-Analysis (PROSPERO 2020: CRD42020188666)." Nutrition and Cancer 74(7): 2351-2364.
	Whey protein has several biochemical characteristics which make it an ideal nutritional supplement in cancer. This meta-analysis aims to evaluate the effects of whey on perioperative outcomes in cancer. A systematic review was conducted as per the Preferred Reporting of Systematic Reviews and Meta-analysis (PRISMA) guidelines. The primary outcome was postoperative complications. Secondary outcomes included 6-minute walk test, length of stay (LOS), and thirty-day readmission. Of the ten trials, six supplemented whey to meet protein requirements of around 1.2 mg/kg/day, and four supplemented whey variably. A synthesis of ten trials with 643 patients showed significantly decreased postoperative complications in the whey supplemented (22%) group as compared to the control (32%) (OR 0.61, 95% CI 0.41-0.90; P = 0.01). Analysis of six trials showed that patients supplemented with whey had greater functional walking capacity before surgery (MD 23.76 meters, 95% CI 4.05-43.47; participants = 377; P = 0.02) and after 4 weeks of surgery (MD 45.76, 95% CI 14.19-77.33; participants = 366; P = 0.004). Thirty-day readmissions and LOS showed no differences. Risk of bias varied between the trials and evidence was moderate to low. Whey protein supplementation improved the perioperative functional capacity and significantly reduced postoperative complications in patients with cancer.Copyright © 2021 Taylor & Francis Group, LLC.

Sriranganathan, D., et al. (2022). "The impact of the ileoanal pouch on female fertility in ulcerative colitis: A systematic review and meta-analysis." Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland.
	BACKGROUND: Ileal pouch-anal anastomosis is a restorative option for patients with ulcerative colitis (UC) requiring surgery. The primary outcome of this study was the relative risk of infertility in females with UC undergoing restorative proctocolectomy compared to the same patients before undergoing restorative proctocolectomy (RPC). Infertility was defined as the inability to conceive after 1 year of regular sexual intercourse without contraception. METHODS: A systematic review and meta-analysis were performed to include all relevant articles from 1946 from MEDLINE, EMBASE and Cochrane central register of controlled trials. Studies included reported on the fertility rate of a cohort with UC and also reported the rate after RPC in those within the cohort who underwent surgery. This study was registered on PROSPERO (CRD42021259745). RESULTS: 13 studies met the inclusion criteria and accounted for 793 patients pre-pouch and 802 post-pouch. The mean and median age of the patients at analysis was 36.8 and 32.7 years respectively; and the median duration of follow-up following IPAA was 110.4 (68-139) months. Our results highlighted that following RPC the relative risk of infertility was 4.17 ([1.99, 8.74] 95% CI) compared with patients before RPC who had ulcerative colitis. CONCLUSIONS: The findings of this meta-analysis provide an update on previous meta-analysis published over a decade ago and results remain congruent. This suggests that despite advancements in surgical techniques the risk to fertility remains similar to a decade ago. However, further high qualities studies are needed to try and decipher independent risk factors associated with a decrease in infertility.

Srisailesh, V., et al. (2021). "Effect of intra-ovarian injection of platelet rich plasma in women with low ovarian reserve or ovarian insufficiency: systematic review and meta-analysis."
	Review question Does intra-ovarian injection of platelet rich plasma in women undergoing IVF/ICSI (in vitro fertilization/intracytoplasmic sperm injection) with low ovarian reserve will improve the fertility outcomes or ovarian reserve markers? Searches A systematic literature search of MEDLINE, EMBASE, CINAHL, Google Scholar, Scopus, Web of Science databases, the Cochrane Library, and SciSearch was conducted on studies that reported on effects of intra-ovarian injections of autologous platelet rich plasma in subfertile women with decreased/low ovarian reserve or premature ovarian insufficiency / failure from inception of database to January 2021. Conference proceedings will be searched and information will be sought from primary authors to investigate whether those studies meet eligibility criteria, and to obtain outcome and study data. Relevant Journals in the Speciality (Human Reproduction, Human Reproduction Update, Reproductive Biomedicine Online and Fertility and Sterility) will be searched for advance access publications. The reference lists of all the included studies will also be also cross-checked. The search strategy will include terms relating/describing population, intervention, comparison and outcomes, and will be adapted for use in each database. Types of study to be included Randomised trials, case-control studies, prospective cohort studies, case series and clinical trials will be included. Studies should include participants who underwent IVF/ICSI with the low ovarian reserve before and after taking an intra-ovarian injection of platelet rich plasma (PRP). Inclusion criteria: Studies comparing the fertility outcomes and ovarian reserve markers before (pre) and after (post) intra-ovarian PRP injection in women who underwent IVF/ICSI with defined low ovarian reserve. In cases of papers with overlapping of data, the studies with the largest number of observations will be included. Exclusion criteria: • Studies that have not defined low ovarian reserve or insufficiency; • Studies that do not have comparator group (reported only on post PRP values of the outcomes); • Studies were excluded if they had no data available for retrieval or overlapping or duplication of the data; • Studies with insufficient data on the outcomes to construct 2x2 table. Any combination of the following criteria was used to define low ovarian reserve: 1. basal FSH >15 IU/L; 2. anti-Müllerian hormone <1 ng/ml; 3. antral follicle count < 5; 4. age with any combination of the above.; 5. Bologna criteria of low ovarian reserve or POSEIDON criteria 3 or 4 with low prognosis ART outcome. Condition or domain being studied Ovarian aging is a physiological process associated with a decline in the quantity and quality of the oocytes stored within the follicular cohort. Age-related physiological decline in the number of follicles has critical implications for fertility. Poor ovarian reserve (POR) indicates decreased ovarian follicular pool in women of reproductive age group. It is an important cause of infertility as large proportion of infertility cases are related to poor ovarian reserve. The delay in childbearing age due to changes in social, lifestyle and environmental circumstances has led to POR. In vitro fertilization (IVF) remains first-line treatment. POR is characterized by poor fertility outcomes due to low and poor oocyte quality. It represents a major challenge in reproductive medicine. The use of donor oocytes provides only hope for but ethical issues, cost, and psychological factors (lack of their own genetic child) limits it use. Platelet rich plasma (PRP) containing high concentrations of platelets with many growth factors is used in regenerative medicine. The ovarian injection of PRP with activated growth factors is hypothesised to arrest and regenerate the ovarian follicular pool. This new innovative therapeutic strategy in POR women may help to improve IVF fertility outcomes with their own oocytes. Participants/population Included participants were infertile couples who underwent IVF/ICSI with low/decreased/diminished/poor ovarian reserve (LOR/DOR/POR) or premature ovarian insufficiency (POI) or premature ovarian failure (POF) before (pre) and after (post) intra-ovarian injection of platelet rich plasma (PRP). Any combination of the following criteria was used to define low ovarian reserve: 1. basal FSH >15 IU/L; 2. anti-Müllerian hormone <1 ng/ml; 3. antral follicle count < 5; 4. age with any combination of the above.; 5. Bologna criteria of low ovarian reserve or POSEIDON criteria 3 or 4 with low prognosis ART outcome. Intervention(s), exposure(s) Intervention: intra-ovarian PRP injection: Preparation of platelet rich plasma (PRP): Peripheral venous blood is drawn (up to 60 ml) from the patient. The collected blood is centrifugated to separate the PRP. Then, the separated PRP is mixed with calcium chloride for activation and release of growth factors. Activated PRP of 2-4 ml will approximately have concentration of > 250000 platelets/µL. Injection of activated PRP into the ovaries: injecting PRP into the ovaries is a technique based on the method of transvaginal oocyte pick up (OPU) procedure. Minimal sedation was administered to the patients. Injection and diffusion into the ovarian stroma were performed under transvaginal ultrasound guided multifocal intramedullary procedure, allowing approximately 2-4 ml PRP for each of both ovaries. The laparoscopic approach may be required if the ovaries are not accessible by transvaginal ultrasound. Data on fertility outcomes(clinical pregnancy rates / number of transferable embryos / number of MII oocytes formed ) and ovarian reserve markers(AFC/AMH/FSH) in participants who underwent IVF/ICSI for low ovarian reserve after the intra ovarian PRP injection. Comparator(s)/control Data on fertility outcomes (clinical pregnancy rates / number of transferable embryos / number of MII oocytes formed) and ovarian reserve markers(AFC/AMH/FSH) in participants who underwent IVF/ICSI for low ovarian reserve before the intra ovarian PRP injection. Context Main outcome(s) Change from the baseline (before / pre-intra-ovarian PRP injection) values of the fertility outcomes and ovarian reserve markers mentioned below after(post) intra-ovarian PRP injection. The fertility outcomes measured pre (before) intra ovarian PRP and post(after) intra ovarian PRP were • clinical pregnancy rates (CPR): Presence of a foetal heartbeat at 6-7 weeks of pregnancy after IVF/ICSI. • number of transferable embryos: number of day 2 (4 cell) / 3 (6-8 cell) Grade 1/2 embryos or day 5(blastocysts) resulted after IVF or ICSI. • number of M II oocytes in IVF/ICSI: number of metaphase II oocytes resulted after IVF/ICSI. The ovarian reserve markers measured pre and post intra ovarian PRP were • Antral Follicle Count (AFC): Defined as the number of follicles measuring 2–10 mm in diameter and is assessed by transvaginal ultrasound. The total number less than 5 in considered low and indicative of low ovarian reserve. • Anti-Mullerian Hormone levels (AMH): AMH level under 1.0 ng/ml is considered low and indicative of a low ovarian reserve. • Follicle Stimulating Hormone levels (FSH): FSH levels > 15 IU/l (day 2-5 of the cycle) is considered high and indicative of low ovarian reserve. Measures of effect Data on fertility outcomes and ovarian reserve markers (both pre and post PRP) were reported as means, standard deviations (SD). Clinical pregnancy outcomes were represented as dichotomous data (as number of events occurred) and remaining outcomes were represented as continuous data(means). The odds ratio was calculated for clinical pregnancy rates and standardized differences in means was calculated for other outcomes with 95% confidence intervals with forest plots. Additional outcome(s) None. Measures of effect Not applicable. Data extraction (selection and coding) After the electronic search has been performed as mentioned above, data extraction will be carried out by selecting the titles and abstracts, and then by retrieveing the full manuscripts of studies that fulfill our selection criteria. They will be independently reviewed by two reviewers (SV & PKA) and conflicts regarding inclusion and exclusion of studies will be resolved by group consensus and with the third reviewer (NM). We will also manually review the bibliographies of retrieved original papers, review papers and relevant studies for additional articles. In this way, missing data from our search criteria will be identified and included. As different databases will be used, search results will be imported into a reference management software (Mendeley) and screened for duplicates that will be excluded. The selection process will be represented in a PRISMA flow chart. Specific data relating to participant numbers and outcomes will then be extracted from the studies selected for inclusion into 2 x 2 tables. Data will be collected in relation to the stated outcomes. Risk of bias (quality) assessment The risk of bias of included studies will be assessed by two independent authors (SV & PKA). This includes item such as study recruitment, outcome assessment, confounding, drop-out and missing data. The risk of bias is assessed using a National Institute of Health (NIH) Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. The quality rating for each of the included studies was presented as Good, Fair, or Poor by two reviewers. Funnel plots will be created to help assess for reporting bias. Strategy for data synthesis We will include the studies with sufficient similarities in design and clinical characteristics for valid pooling. Presence of heterogeneity will be evaluated by the I² statistic. An I² >50% was taken to indicate substantial heterogeneity. Heterogeneity of the exposure effects was evaluated graphically using forest plots and statistically using the I² statistic to quantify heterogeneity across studies. The random effects model was used if the I² statistic was greater than 50%. Exploration of the causes of heterogeneity was planned using variation in features of population, exposure, and study quality. Sensitivity analyses was used where possible and appropriate to address the clinical and methodological variations. For each outcome, data will be extracted in 2 × 2 tables. Any missing data on the changes of standard deviations from the included studies will be imputed by correction factor(Pre/Post correlation value of 0.5 after reasoned argument and doing sensitive analysis) of 0.5 will be added to all cells in the 2 × 2 table for the calculation. One group (pre-post) treatment effect meta-analysis will be done to look at the effect of intraovarian PRP intervention. Pre intraovarian values of the outcomes mentioned will be the comparative group. The odds ratio will be calculated for clinical pregnancy rates and standardized differences in means for other outcomes with 95% confidence intervals with forest plots. The pooled estimates will be obtained using Comprehensive Meta-Analysis Version 3.0 Funnel plots will be created to help assess for reporting bias. Analysis of subgroups or subsets None planned. Contact details for further information Srisailesh Vitthala sri.vitthala@abdn.ac.uk Organisational affiliation of the review Aberdeen Fertility Centre, Aberdeen Maternity & Royal Infirmary, Aberdeen, U.K. https://www.aberdeenfertility.org.uk Review team members and their organisational affiliations Mr Srisailesh Vitthala. Aberdeen Fertility Centre, Aberdeen Maternity & Royal Infirmary, Aberdeen, U.K Professor Prashanth Kumar Adiga. Kasturba Medical College, MAHE, Manipal, Karnataka, India Dr Nicola Marconi. Aberdeen Fertility Centre, Aberdeen Maternity & Royal Infirmary, Aberdeen, U.K Dr Ravi Shankar N.. Vallabhbhai Patel Chest Institute, University of Delhi, India Type and method of review Intervention, Meta-analysis, Systematic review Anticipated or actual start date 30 April 2021 Anticipated completion date [1 change] 31 March 2022 Funding sources/sponsors None Conflicts of interest Language English Country India, Scotland Stage of review [1 change] Review Completed not published Subject index terms status Subject indexing assigned by CRD Subject index terms Biomarkers; Female; Fertility; Fertilization in Vitro; Humans; Infertility, Female; Injections; Ovarian Diseases; Ovarian Reserve; Platelet-Rich Plasma; Pregnancy; Pregnancy Rate; Primary Ovarian Insufficiency; Sperm Injections, Intracytoplasmic; Treatment Outcome

Srivastava, S., et al. (2022). "Dosimetric comparison of ACE algorithm and TG-43 formalism in HDR brachytherapy of carcinoma cervix." Radiotherapy and Oncology 170(Supplement 1): S266.
	Purpose or Objective TG-43 formalism has been widely used in brachytherapy for dose calculation. However, this method does not consider the tissue and applicator heterogeneities. In the present study, we have compared the effect of model-based dose calculation algorithms like Advanced Collapsed cone Engine (ACE) on dose calculation with the TG-43 dose calculation formalism in patients with cervical carcinoma. Materials and Methods 8 patients with 24 CT data sets of HDR intracavitary brachytherapy plans in cervical cancer were retrospectively studied. HR-CTV and organs at risk (OAR) were contoured in the Oncentra treatment planning system using GYN GEC-ESTRO guidelines. Patients were planned for 7 Gy per fraction for 3 fractions. Plans were initially calculated using TG 43 formalism and then recalculated using the ACE (Elekta, Stockholm, Sweden) algorithm with applicator models selected from the applicator library. The dosimetric parameters of TG-43 and ACE-based plans were compared in terms of target coverage (V100, D90, D100), OAR doses (D2cc, D1cc, and D0.1cc), homogeneity index (HI), and conformity index (CI). Results The mean percentage difference between right point A values of TG-43 and ACE was -0.08+/-0.27%. For HR-CTV, the average D90 values for TG-43 and ACE calculated plans were 5.27+/-1.17 Gy and 5.27+/-1.16 Gy respectively. The mean percentage difference for doses D90 and D100 was found to be -0.02+/-0.59 % and 0.60+/-1.18% respectively. The average V100 values for TG-43 and ACE calculated plans were 74.80+/-13.90% and 74.83+/-13.31% respectively. For bladder, the mean percentage differences for D2cc, D1cc, and D0.1cc values between TG-43 and ACE were -0.39+/-0.61%, -0.40+/-0.59%, and -0.28+/-0.54 % respectively. In the case of the rectum, the mean percentage differences for D2cc, D1cc, and D0.1cc values between TG- 43 and ACE were -0.21+/-0.59%, -0.20+/-0.55%, and -0.15+/-0.47% respectively. Similarly, for sigmoid these values were 0.27+/-1.19%, 0.20+/-0.98% and 0.14+/-0.67% respectively. Conclusion The ACE improved the dose accuracy compared to the TG-43 formalism. However, we did not find any significant difference between the dose-volume parameters of TG-43 and ACE calculated plans.Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Srivastava, S., et al. (2022). "Dosimetric Evaluation of Different Optimization Algorithms Used in Interstitial Brachytherapy of Cervical Carcinoma." Journal of Biomedical Physics and Engineering 12(4): 339-348.
	Background: Conventional optimization techniques are based on the planning approach in which positions and weights are varied to generate the desired dose distribu-tion. Inverse planning simulated annealing (IPSA) is an advanced optimization method developed to automatically determine a suitable combination of positions to design an acceptable plan. Objective(s): In this study, three optimization techniques namely IPSA, graphical optimization (GROPT), and geometrical optimization (GOPT) methods are compared in high-dose-rate interstitial brachytherapy of cervical carcinoma. Material(s) and Method(s): In this retrospective study, twenty computed tomog-raphy (CT) data sets of 10 cervical cancer patients treated with Martinez Universal Perineal Interstitial Template-based interstitial brachytherapy were studied. The treatment plans generated were optimized using the IPSA, and GOPT methods. The pre-scribed dose was 24 Gy in 4 fractions. Plans produced using IPSA, GrOPT, and GOPT techniques were analyzed for comparison of dosimetric parameters, including target coverage, homogeneity, conformity, and organs at risk (OAR) doses. Result(s): V100 values for IPSA, GrOPT and GOPT plans were 95.81+/-2.33%, 93.12+/-2.76% and 88.90+/-4.95%, respectively. The mean D90 values for the IPSA, GrOPT, and GOPT plans were 6.45+/-0.15 Gy, 6.12+/-0.21 Gy, and 5.85+/-0.57 Gy, respectively. Significantly lower doses of OAR were in the IPSA plans that were more homogeneous (HI=0.66). Conformity was comparatively higher in IPSA-based plans (CI=0.75). Conclusion(s): IPSA plans were superior and resulted in better target coverage, homogeneity, conformity, and minimal OAR doses. Copyright © Journal of Biomedical Physics and Engineering.

Sroussi, J., et al. (2022). "Does hyaluronic acid gel reduce intrauterine adhesions after dilation and curettage in women with miscarriage? A Multicentric randomized controlled trial (HYFACO Study)." American Journal of Obstetrics and Gynecology 227(4): 597.e591-597.e598.
	Background: Miscarriage is a frequent problem that requires dilation and curettage in 30% of cases. This routine surgery may lead to intrauterine adhesions and severe infertility. Hyaluronic acid gel is known to reduce intrauterine adhesions after hysteroscopic surgery.; Objective: This study aimed to evaluate the rate of intrauterine adhesions after dilation and curettage for miscarriage with and without hyaluronic acid gel.; Study Design: This was a multicentric (9 hospitals in France), prospective, open-label randomized trial. Patients who had a miscarriage between weeks 7 and 14 of gestation, required dilation and curettage, and wanted another pregnancy were eligible for the study. Women were randomly assigned in a 1:1 ratio to surgery alone (control group) or surgery with intrauterine instillation of hyaluronic acid gel (gel group). An office hysteroscopy was planned at 6 to 8 weeks after surgery. The primary endpoint was the rate of intrauterine adhesions during this office follow-up hysteroscopy. Two different follow-up fertility surveys were sent at 6 months and 1 year after the end of the intervention, respectively.; Results: Among the 343 patients who had curettage, 278 had hysteroscopy. After multiple imputation, the rate of intrauterine adhesions was lower in the gel group than in the control group (9.1% vs 18.4%, respectively; P=.0171). Among the 110 responders to the surveys, the overall pregnancy rate at 12 months after surgery was 64.5% (71/110), and similar in both groups (57.4% [27/47] in the control group vs 69.8% [44/63] in the gel group; P=.1789).; Conclusion: Intrauterine instillation of hyaluronic acid gel reduces the rate of intrauterine adhesions in women treated with dilation and curettage for miscarriage. (Copyright © 2022 Elsevier Inc. All rights reserved.)

ssvytb, R. B. R. (2021). "Relaxation with Guided Image for patients in treatment of radiotherapy combined to chemotherapy randomized clinical trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Control group: three Quality of Life assessments will be carried out using the FACT‐Cx version 4 questionnaire: in the first, fourth and sixth weeks of chemotherapy treatment combined with radiotherapy. Patients were also assessed for anxiety using the STAI Anxiety Trait‐State questionnaire, three times a week, during combined chemotherapy and radiation therapy. E02.190.463 E02.190.525.875 CONDITION: Uterine Cervical Neoplasms PRIMARY OUTCOME: It was intended to as an outcome the improvement of QVRS of patients with CC submitted to chemoradiotherapy, measured by the questionnaire FACT‐Vs version 4 during their treatment. The analysis of the QVRS assessment instrument was carried out according to FACIT guidelines. The higher score found, the better the QVRS, considering the reverse scores of the negative items in such interpretation. SECONDARY OUTCOME: As a secondary outcome, it was intended to evaluate the effects of Guided Image Relaxation on the anxiety of patients treated with chemoradiotherapy for CC, measured by the anxiety assessment questionnaires IDATE TRACO‐ESTADO. The data analysis was by means of verification is scores in which the values vary from 20 to 80 (Likert scale from 1 to 4); in positive question, the score is reversed, the higher the score, the greater the anxiety. INCLUSION CRITERIA: Women over the age of 18 undergoing combined chemotherapy and radiation therapy for cervical cancer

Staack, A., et al. (2022). "The Impact of Caffeine Intake on Mental Health Symptoms in Postmenopausal Females with Overactive Bladder Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial." Journal of women's health (2002) 31(6): 819-825.
	Background: Caffeine has been associated with a dose-dependent variety of mental health changes, which have been found to precede or be a complication of overactive bladder (OAB) symptoms after menopause. The current study examines the effects of low and moderate caffeine intake on anxiety, depression, sleep, and stress in postmenopausal females with OAB. Materials and Methods: Eighty-one females were randomized in a prospective, double-blind, placebo-controlled study. Participants were allocated to 200 mg/day caffeine, 400 mg/day caffeine, and placebo capsules for 1 week each in a crossover design and evaluated using validated mental health questionnaires. Symptoms during each treatment phase were measured using Beck Anxiety and Depression Inventory, Insomnia Severity Index, and Perceived Stress Scale. Linear regression models were used to examine the impact of low (200 mg/day) and moderate (400 mg/day) dose of caffeine and placebo on mental health. Results: Fifty-six female participants finished the study. The mean age was 69.2 years (58.0-84.0 years). Two females dropped out during the treatment phase with 400 mg/day caffeine intake due to side effects associated with headaches and nausea. Moderate dose of caffeine showed a small positive effect on mental health, specifically a decrease in anxiety during 7 days of exposure ( p < 0.05). Conclusions: Moderate caffeine use may decrease anxiety in postmenopausal patients with underlying OAB, whereas depression, insomnia, and perceived stress were not affected by low-to-moderate caffeine intake. Our results support that counseling efforts on moderate caffeine consumption in postmenopausal patients underline that low-to moderate caffeine intake may be appropriate and possibly beneficial unless contraindicated due to other underlying conditions. Clinical Trials Registration: clinicaltrials.gov (NCT02180048).

Stafne, S. N., et al. (2022). "Antenatal pelvic floor muscle training and urinary incontinence: a randomized controlled 7-year follow-up study." International Urogynecology Journal 33(6): 1557-1565.
	Introduction and hypothesis: Urinary incontinence is common postpartum. Our aims were to assess whether antenatal exercise including pelvic floor muscle training (PFMT) has long-term effects on urinary incontinence (UI) and to explore factors associated with UI 7 years postpartum. Method(s): A follow-up of a two-centre randomized controlled trial performed at St. Olavs Hospital and Stavanger University Hospital, Norway. In the original trial women were randomized to a 12-week structured exercise protocol including PFMT or standard antenatal care during pregnancy. Link to an electronic questionnaire was sent by postal mail 7 years postpartum. Prevalence of UI was assessed with Sandvik severity index and compared between groups. Factors associated with UI were studied using multivariable logistic regression analysis. Result(s): The response rate was 35% (298/855). UI was reported by 78 (51%) in the intervention group and 63 (57%) in the control group (p = 0.539). In the multivariable logistic regression analyses, women with UI at inclusion had a five-fold increase in odds of UI at 7 years (OR 5.4, 95% CI 2.6, 11.5). Engaging in regular exercise was not significantly associated with UI at 7 years; however, UI was associated with lower exercise intensity (OR 2.4, 95% CI 1.2, 4.6). Conclusion(s): We found no group differences of antenatal exercise including PFMT on UI after 7 years among the responders. UI in pregnancy increased the risk of long-term UI. Regular exercise was not associated with UI at 7 years; however, women with UI were more than twice as likely to exercise at lower intensity than continent women.Copyright © 2021, The Author(s).

Stalder, S. A., et al. (2023). "bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction." BJU International 132(3): 343‐352.
	OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham‐controlled, double‐blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self‐Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow‐up assessments at the study end.

Stamenov, G. S., et al. (2022). "Hysteroscopy and female infertility: a fresh look to a busy corner." Human Fertility 25(3): 430-446.
	Hysteroscopy has evolved from the traditional art of examining the uterine cavity for diagnostic purposes to an invaluable modality to concomitantly diagnose and (see and) treat a multitude of intrauterine pathologies, especially in the field and clinics specialising in female reproduction. This article reviews the literature on the most common cervical, endometrial, uterine and tubal pathologies such as chronic endometritis, endometrial polyps, adenomyosis, endometriosis, endometrial atrophy, adhesions, endometrial hyperplasia, cancer, and uterine malformations. The aim is to determine the efficiency of hysteroscopy compared with other available techniques as a diagnostic and treatment tool and its association with the success of in vitro fertilisation procedures. Although hysteroscopy requires an experienced operator for optimal results and is still an invasive procedure, it has the unique advantage of combining great diagnostic and treatment opportunities before and after ART procedures. In conclusion, hysteroscopy should be recommended as a first-line procedure in all cases with female infertility, and a special effort should be made for its implementation in the development of new high-tech procedures for identification and treatment infertility-associated conditions.Copyright © 2020 The British Fertility Society.

Stanca, M., et al. (2022). "Long-Term Survival, Prognostic Factors, and Quality of Life of Patients Undergoing Pelvic Exenteration for Cervical Cancer." Cancers 14(9).
	Background: Considerable efforts have been carried out over the past 30 years to support patients with advanced cervical cancer. Throughout this time, Eastern European countries have been left aside from the decision-making groups on this matter, hence the absence of similar studies in this geographical area. In these countries, the quality of life (QoL) of patients with cervical cancer might be considered a “caprice”, and the discomforts they encounter following pelvic exenteration for cervical cancer are often perceived as a “normal phenomenon”. Methods: This study examined forty-seven patients submitted to pelvic exenteration followed up for nine years after the surgical intervention. The first objective of this study is to identify the prognostic factors that influence the overall survival (OS) of patients undergoing pelvic exenteration for FIGO stage IVA, recurrent or persistent cervical cancer after previous conclusive treatments. The second objective is to assess the QoL of the surviving patients using the QLQ-C30 and QLQ-CX24 standardized questionnaires. Results: The mean age of the participants was 54 years (range 36−67). At the time of the study, there were 25 living patients (53.2%), the 3-year OS was 61%, and the 5-year OS was 48.7%. Cox regression analysis recognized parameter invasion, pelvic lymph node metastases, positive resection margins, early postoperative complications, and infralevatorian pelvic exenteration as negative prognostic factors influencing the OS (p < 0.05). Of the 25 survivors, 18 patients answered the QoL questionnaires. The cost of favorable survival has been translated into poor overall QoL, unsatisfactory functional, social, and symptom scores, a high prevalence of cervical cancer-specific symptoms such as lymphedema, peripheral neuropathy, severe menopausal symptoms, distorted body image, and lack of sexual desire. The lower scores are comparable to the only three studies available in the literature that assessed the QoL of patients undergoing pelvic exenteration precisely for cervical cancer. Conclusions: Despite its retrospective nature and some limitations, this paper, similar to other studies, shows a decent OS but with a marked adverse impact on QoL, suggesting the importance of adequate psycho-emotional and financial support for these patients following pelvic exenteration. This study also contributes to the current knowledge regarding advanced cervical cancer treatment, depicting survival, prognostic factors, and QoL of patients undergoing pelvic exenteration for cervical cancer in a reference center in Eastern Europe. Our study can provide a comparison for future prospective randomized trials needed to confirm these results.

Stanhope Kaitlyn, K., et al. (2024). "Short Term Coping-Behaviors and Postpartum Health in a Population-Based Study of Women with a Live Birth, Stillbirth, or Neonatal Death." Maternal and Child Health Journal.
	Objective: Responding to the National Institutes of Health Working Group's call for research on the psychological impact of stillbirth, we compared coping-related behaviors by outcome of an index birth (surviving live birth or perinatal loss - stillbirth or neonatal death) and, among individuals with loss, characterized coping strategies and their association with depressive symptoms 6-36 months postpartum.; Methods: We used data from the Stillbirth Collaborative Research Network follow-up study (2006-2008) of 285 individuals who experienced a stillbirth, 691 a livebirth, and 49 a neonatal death. We conducted a thematic analysis of coping strategies individuals recommended following their loss. We fit logistic regression models, accounting for sampling and inverse probability of follow-up weights to estimate associations between pregnancy outcomes and coping-related behaviors and, separately, coping strategies and probable depression (Edinburgh Postnatal Depression Scale > 12) for those with loss.; Results: Compared to those with a surviving live birth and adjusting for pre-pregnancy drinking and smoking, history of stillbirth, and age, individuals who experienced a loss were more likely to report increased drinking or smoking in the two months postpartum (adjusted OR: 2.7, 95% CI = 1.4-5.4). Those who smoked or drank more had greater odds of probable depression at 6 to 36 months postpartum (adjusted OR 6.4, 95% CI = 2.5-16.4). Among those with loss, recommended coping strategies commonly included communication, support groups, memorializing the loss, and spirituality.; Discussion: Access to a variety of evidence-based and culturally-appropriate positive coping strategies may help individuals experiencing perinatal loss avoid adverse health consequences. (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stankiewicz, K., et al. (2019). "Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA): A Trial Protocol." JAMA Network Open 2(4): e190819.
	Importance: Human papillomavirus (HPV), particularly HPV type 16, causes most anal and vulvar high-grade squamous intraepithelial lesions (HSIL), which are precursors to cancer. After initial treatment of HSIL, more than 30% of patients will have disease recurrence, with even higher recurrence among HIV-positive individuals and men who have sex with men. Recurrences can be debilitating and lead to significant morbidity and medical expense. Observational studies suggest a possible therapeutic benefit of the licensed HPV vaccines in reducing recurrent lesions in previously infected persons.; Objective: To test whether the licensed prophylactic HPV vaccine (Gardasil-9) can reduce the risk of HSIL recurrence by 50% in previously unvaccinated individuals recently treated for anal or vulvar HSIL.; Design, Setting, and Participants: This is a trial protocol for a randomized, double-blind, placebo-controlled, proof-of-concept clinical trial. Eligible participants are aged 27 to 69 at study start and have not received prior HPV vaccination, have had anal or vulvar HSIL diagnosed on or after January 1, 2014, and have no evidence of HSIL recurrence at screening. Persons infected with HIV are eligible for the study provided they are receiving antiretroviral therapy. Target enrollment is 345 individuals. The primary outcome is time to histopathologically confirmed recurrence of HSIL. Differences in the risk for recurrence of HSIL will be evaluated using Cox proportional hazard models. Additional analyses include (1) frequency of HSIL recurrence; (2) role of HPV antibodies in deterring recurrence; (3) role of HPV persistence in recurrence, as measured by HPV genotype or HPV-16 variant lineage determined using swab samples collected at months 0, 18, and 36; and (4) incidence of adverse events. The study will be conducted at the University of Washington Virology Research Clinic from 2017 through 2022. Participants will be followed up for up to 36 months in the clinic, and up to 42 months by telephone.; Discussion: Management of persistent or rapidly recurring anogenital HSIL remains challenging. Results from this study will provide evidence on whether incorporating the nonavalent HPV vaccine into routine care can decrease recurrence of anal and vulvar HSIL.; Trial Registration: ClinicalTrials.gov identifier: NCT03051516.

Stankiewicz, M. A. (2023). "High-Dose-Rate Brachytherapy for Cervical Cancer - Comparison of Two Fractionation Schedules." Brachytherapy 22(5 Supplement): S89-S90.
	Purpose: High-dose-rate (HDR) brachytherapy is a vital part of treatment in patients with locally advanced cervical cancer. Current guidelines recommend the use of image-guided adaptive brachytherapy (IGABT). Several fractionation schedules are used in external beam radiotherapy (EBRT) and brachytherapy (BT). A retrospective analysis of patients treated with radio(chemo)therapy and HDR brachytherapy due to cervical cancer was conducted. We compared the efficacy of two fractionation schedules implemented in our department. Material(s) and Method(s): Schedule one ("5x6 Gy") consisted of five fractions of 6 Gy delivered within 2.5 weeks. In the majority of patients, the dose was prescribed to point A. Schedule two ("4x7 Gy") consisted of four fractions of 7 Gy delivered within two weeks. In all patients, the dose was prescribed to CTV. Local control (LC) and distant metastasis-free survival (DMFS) were calculated. The Kaplan-Meier estimator, log-rank and Mann-Whitney U test were used in statistical analysis. One hundred seventeen patients were included in this analysis. Median age was 57 years (range: 29 - 79). The disease stage was re-assessed according to FIGO 2018 classification. Forty-five percent of patients had FIGO IIIC1 disease, 29% - FIGO IIIB, 15% - FIGO IIB and 6% - FIGO IIIC2. The vast majority of patients (96%) had were diagnosed with planoepithelial carcinoma, 2,5% with cervical adenocarcinoma, one patient with clear cell carcinoma and one with serous carcinoma. The "5x6 Gy" fractionation was administered in 79% of patients. The median overall treatment time (OTT) was 58 days (range: 45 - 139 days). The median CTV D90 EQD2 sum of EBRT and BT was 89 Gy (range: 65 - 114 Gy). Result(s): In the "5x6 Gy" subgroup, the follow-up was significantly longer (p=0.00006), CTV D90 EQD2 was significantly higher (p=0.0001), and OTT was significantly longer (p=0.02). No other significant differences were observed between the subgroups. They were well balanced in terms of patients' age (p=0.6), histopathological grade of the tumour (p=0.2) and FIGO stage (p=0.07). In the whole group, 5-year LC was 91%, 5-year regional nodal control was 86%, and 5-year DMFS was 80%. The comparison of the two fractionation schedules ("5x6 Gy" vs "4x7 Gy") revealed that higher CTV D90 EQD2 was not associated with better local or distant control. There were no differences in LC (p=0.79), regional nodal control (p=0.7) or DMFS (p=0.83) between the subgroups. However, better regional nodal control and longer DMFS were observed in patients with OTT<=60 days (p=0.035 and p=0.017, respectively). Conclusion(s): Both fractionation schedules have similar efficacy. A shorter overall treatment time is associated with better regional nodal control and DMFS. However, a longer follow-up is needed to confirm these findings.Copyright © 2023

Starks, D., et al. (2022). "Patient Reported Outcomes and Final Results of Phase 1 Evaluation of the Safety and Clinical Activity of Sapanisertib in Combination with Serabelisib and Paclitaxel in Patients with Advanced Ovarian, Endometrial, or Breast Cancer (044)." Gynecologic Oncology 166(Supplement 1): S30-S31.
	Objectives: To evaluate the safety, efficacy, and patient-reported outcomes of the combination of paclitaxel, sapanisertib, and serabelisib. Method(s): This is an open-label cohort study of sapanisertib (TAK-228) and serabelisib (TAK-117) given on days 2-4, 9-11, 16-18, and 23-25 with paclitaxel on days 1, 8, and 15 of a 28-day cycle. A traditional 3+3 dose escalation design with a maximum of five dosing cohorts was used. All five cohorts plus an expansion cohort were presented. Patient-reported outcomes utilizing the Therapy-Related Symptom Checklist (TRSC) and Health-Related Quality of Life - Linear Analogue Self-Assessment (HRQOL-LASA) were also evaluated. Result(s): Enrollment has been completed, and the overall results are summarized in Table 1. Nineteen patients have been enrolled, a majority of which were heavily pretreated, with the average number of prior regimens exceeding four. Overall, the combination of the three drugs was well-tolerated, except by patients in cohort 5. One dose-limiting toxicity occurred in the last patient enrolled. About 503 adverse events have been reported to date, but only 45 (9%) grade 3 or 4 events. Results of the TRSC and HRQOL show that patients generally tolerated the therapy well and maintained or improved their quality of life while on therapy in cohorts 1-4. As expected, patients with higher symptom scores had a corresponding diminished quality of life. Three patients had a complete response (CR), four had a partial response (PR), and four patients had stable disease (SD). The overall response rate is currently 47% in 15 evaluable patients. The clinical benefit rate is 73%, and the progression-free survival currently stands at approximately 11 months. All patients received comprehensive genomic profiling, and seven patients had received prior everolimus or temsirolimus. Conclusion(s): Overall, the combination of sapanisertib, serabelisib, and paclitaxel was safe and well-tolerated throughout the first four cohorts. Preliminary efficacy results appear very promising, especially for patients with PI3K/AKT/mTOR pathway mutations. The positive effects of the combination were routinely seen in the lowest dosing cohorts, and clinical benefit was even seen in patients who had previously failed everolimus or temsirolimus. There were few serious adverse events, and most side effects were managed with routine supportive care interventions. Data from the HRQOL and TRSC confirm that this combination was well tolerated and support further evaluation of this therapy.[Formula presented]Copyright © 2022 Elsevier Inc.

Starzec-Proserpio, M., et al. (2023). "Not all lasers are the same: a scoping review evaluating laser therapy for vulvodynia." Sexual Medicine Reviews 12(1): 14-25.
	Introduction: Lasers are commonly used for treating various vaginal/vulvar conditions. To date, there is to our knowledge no available literature review on the effects of different types of lasers for the treatment of women with vulvodynia, a condition that causes chronic pain in the vulvar area.; Objectives: We sought to review the literature and summarize the existing published evidence regarding the effects of lasers for the treatment of women with vulvodynia.; Methods: A scoping review with a systematic search was conducted that included studies investigating the use of laser treatment in women with vulvodynia. The National Heart, Lung, and Blood Institute Study Quality Assessment Tools were used for the quality assessment. The type of laser, effects on pain and function, and participants' perceived improvement as well as adverse events were analyzed.; Results: Eight studies investigating laser therapy were included in the analysis: 1 randomized controlled trial, 5 before-after studies, 1 nonrandomized intervention study, and 1 case report. Several types of laser therapies were identified, ranging from mild noninvasive photobiomodulation to more invasive ablative procedures. Of the 6 studies that included pain outcomes, 3 studies showed statistically significant improvements from baseline to follow-up, and 3 demonstrated a reduction in pain from subjectively interpreted data. Similarly, each of the 2 studies investigating sexual function also reported an improvement (based only on subjective interpretation). Of the 2 studies with a comparison group, neither study was adequately powered to detect between-group differences. Furthermore, 57%-78% of participants reported improvement, with 1 study showing a greater statistically significant improvement in the low-level laser therapy patient group compared to the sham laser group. Outcomes and adverse events varied depending on the type of laser used.; Conclusions: Although these studies demonstrated some benefits of laser therapy for the treatment of vulvodynia, these findings should be interpreted with caution given the scarcity of the included studies that were robust and sufficiently powered. Future research should focus on conducting well-designed randomized controlled trials to evaluate the efficacy of different types of lasers in the treatment of vulvodynia. (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Starzec-Proserpio, M., et al. (2022). "High-Intensity Laser Therapy (HILT) as an Emerging Treatment for Vulvodynia and Chronic Musculoskeletal Pain Disorders: A Systematic Review of Treatment Efficacy." Journal of Clinical Medicine 11(13).
	High-intensity laser therapy (HILT) has been gaining popularity in the treatment of chronic musculoskeletal pain, including vulvodynia. The objective of this study was to critically appraise and synthesize the available evidence on the efficacy of HILT for reducing pain and improving function in vulvodynia and other chronic primary musculoskeletal pain conditions. Electronic databases and the grey literature were searched. Effects on pain intensity, function, and adverse events were assessed. One study investigating HILT in the treatment of vulvodynia and 13 studies on the treatment of chronic musculoskeletal pain were selected. The study assessing vulvodynia showed favorable results for reducing pain. Regarding chronic musculoskeletal pain, 12 out of the 13 studies selected consistently showed that HILT was more effective than the placebo/active comparator for reducing pain and improving function. The available effect sizes for pain showed large to huge effects. Similar effects were observed for function except for two studies showing moderate effects. The GRADE score was moderate. Conclusions: There are insufficient data to support the use of HILT in vulvodynia, but the promising results encourage further research. HILT appears to be effective in musculoskeletal pain conditions. More high-quality studies are needed to identify effective laser protocols.

Steardo, L., Jr., et al. (2019). "Psychoeducational Intervention for Perinatal Depression: Study Protocol of a Randomized Controlled Trial." Frontiers in Psychiatry 10: 55.
	Perinatal depression (PD) is a severe and disabling condition impacting negatively on children in terms of adverse neonatal outcomes and on the well-being of women and their families. All pregnant women attending the unit of Gynecology and Obstetrics Service of the University of Campania "L. Vanvitelli" will be screened for PD using the Edinburgh Postpartum Depression Scale (EPDS). Women with a score ≥10 at the EPDS will be invited to receive a full psychiatric assessment. The required sample size is of 126 women with PD which will be randomly allocated to either an experimental group, receiving a uni-familiar psychoeducational intervention, or to a control group, receiving the Best Treatment Option (BTO). Patients will be evaluated through several assessment instruments: Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), Manchester Short Assessment of Quality of Life (MANSA), Family Assessment Device (FAD), Family Coping Questionnaire (FCQ), and Pattern of Care Schedule (PCS). Patients will be evaluated at baseline, 3, 6, 9, and 12 months post-randomization. The severity of depressive symptoms at the HAM-D scale has been selected as primary outcome. Other outcome measures include improvement in the severity of anxiety symptoms, of global and personal functioning, an improvement in family members' coping strategies and in the level of quality of life. It has been highlighted the importance of developing screening and treating programs for PD, and our study will use rigorous study design to evaluate the efficacy of the adaption of a well-known family psychoeducational model to the treatment of PD. The aims of present trial are to: (1) develop an informative package for pregnant women with PD; (2) promote a screening programme for PD; (3) identify those (socio-demographic and pregnancy-related environmental) factors associated with a higher risk to develop a perinatal or postnatal depression; (4) evaluate the efficacy of a new experimental psychoeducational intervention in reducing the depressive symptoms during pregnancy compared to the BTO.

Steenland Maria, W. and N. Trivedi Amal (2023). "Association of Medicaid Expansion With Postpartum Depression Treatment in Arkansas." JAMA health forum 4(2): e225603.
	Importance: Postpartum depression affects approximately 1 in every 8 postpartum individuals in the US. Antidepressant medication can effectively treat postpartum depression. However, gaps in postpartum insurance coverage after the end of Medicaid pregnancy coverage at 60 days postpartum may limit treatment uptake and decrease continuity of postpartum depression treatment.; Objective: To examine the association of Medicaid expansion in Arkansas with postpartum antidepressant prescription fills and antidepressant continuation and supply during the first 6 months postpartum.; Design, Setting, and Participants: Cohort study with a difference-in-differences analysis comparing persons with Medicaid and commercially financed childbirth using Arkansas' All-Payer Claims Database (2013-2016). Analysis was completed between July 2021 and June 2022.; Exposures: Medicaid-paid childbirth after January 1, 2014.; Main Outcomes and Measures: Antidepressant medication prescription fills and the number of days of antidepressant supply in the early (first 60 days after childbirth) and the late (61 days to 6 months after childbirth) postpartum periods.; Results: In this cohort study with a difference-in-differences analysis of 60 990 childbirths (mean [SD] birthing parent's age, 27 [5.3] years; 22% Black, 7% Hispanic, 67% White individuals), 72% of births were paid for by Medicaid and 28% were paid for by a commercial payer. Before expansion, 4.2% of people with a Medicaid-paid birth filled an antidepressant prescription in the later postpartum period. Medicaid expansion was associated with a 4.6 percentage point (95% CI, 2.9-6.3) increase in the likelihood, or a relative change of 110%, in this outcome. Before expansion, among people with postpartum depression in the early postpartum period with a Medicaid-paid birth, 32.7% filled an antidepressant prescription in the later postpartum period, and had an average of 23 days of antidepressant prescription supply during the later postpartum period. Among people with early postpartum depression, Medicaid expansion increased the continuity of antidepressant treatment by 20.5 percentage points (95% CI, 14.1-26.9) and the number of days with antidepressant supply in the later postpartum period by 14.1 days (95% CI, 7.2-20.9).; Conclusions and Relevance: Medicaid expansion in Arkansas was associated with an increase in postpartum antidepressant prescription fills, and an increase in antidepressant treatment continuity and medication supply in the period after Medicaid pregnancy-related eligibility ended.

Steenland, M. W. and A. N. Trivedi (2023). "Association of Medicaid Expansion with Postpartum Depression Treatment in Arkansas." Obstetrical and Gynecological Survey 78(8): 458-459.
	Approximately 1 in 8 individuals experience postpartum depression in the United States. Among them, 17% had their care covered by Medicaid and 10% had their care covered by a commercial payer. Postpartum depression is also more common among American Indian/Alaska Native (22%), Asian/Pacific Islander (19%), and Black (18%) individuals than White individuals (11%). Adverse postpartum health outcomes include reduced maternal quality of life, greater difficulty with social and partner relationships, increased odds of unemployment, and adverse child health outcomes. Effective treatments for postpartum depression include antidepressant medications and psychotherapy. Yet, these therapies are often underused, particularly among Medicaid enrollees and Black individuals, due to systemic racism and lack of access to health care, childcare, and transportation. One solution that has been suggested includes expanding Medicaid coverage to a year postpartum. One study in Oregon found that Medicaid expansion increased screening for and treatment of postpartum depression. The aim of this study was to compare the differences in treatment for postpartum depression among individuals whose births were covered by Medicaid versus commercial payers. This was a cohort study conducted in Arkansas with a difference-in-differences regression design. Data were collected from the state's birth certificate records and all-payer claims database. Included were all births between January and June 2013, when Medicaid postpartum coverage ended 60 days after childbirth, and between January 2014 and December 2015, after the state expanded Medicaid postpartum coverage beyond 60 days if the individual's income was below 138% of the federal poverty level. The primary outcomes were the filling of >=1 antidepressant prescriptions and the number of days supplied in the first 60 days (early postpartum period) and 61 days to 6 months after childbirth (later postpartum period). The secondary outcomes were psychotherapy visits and a diagnosis of depression in the 6 months after childbirth. A total of 60,990 individuals gave birth in Arkansas between 2013 and 2015. Of these births, 71.7% were covered by Medicaid and 28.3% by commercial payers. Compared with individuals with commercially paid births, individuals who had a Medicaid-covered birth were younger (mean age, 25.5 vs 29.4 years), more likely to identify as Hispanic (10.8% vs 3.0%), and less likely to have a college or higher level of education (5.1% vs 55.5%). In the later postpartum period, 4.2% of those with Medicaid coverage filled a prescription for antidepressants before the expansion of Medicaid. In 2015, with Medicaid expansion, the likelihood of filling an antidepressant prescription in the later postpartum period increased by 110% (adjusted difference-in-differences, 4.6; 95% confidence interval [CI], 2.9-6.3). Similarly, in the early postpartum period, the likelihood of individuals with Medicaid filling an antidepressant prescription increased by 28% (adjusted difference-in-differences, 1.9; 95% CI, 0.2-3.7). The percentages of individuals with commercial coverage who filled antidepressant prescriptions did not change between 2013 and 2015. Before expansion, 0.2% of individuals with Medicaid coverage and 1.3% of those with commercial coverage had psychotherapy visit in the later postpartum period. This increased by 0.8 percentage points (95% CI, 0.5-1.2) after Medicaid was expanded. No change was associated with Medicaid expansion in the early postpartum period. Before Medicaid expansion, individuals with commercial coverage who had been diagnosed with depression within the first 60 days postpartum received an average 72-day supply of antidepressants in the later postpartum period, compared with those with Medicaid coverage who received a 23-day supply (95% CI, 20.7-25.4). Medicaid expansion was associated with a 61% increase in antidepressant prescriptions filled. In conclusion, Medicaid expansion in Arkansas helped to narrow the disparity of postpartum care between individuals covered by Medica d and those covered by commercial payers. After the expansion of Medicaid in 2014, more Medicaid enrollees filled antidepressant prescriptions, underwent psychotherapy, had greater continuity of treatment for postpartum depression, and had an increased antidepressant supply beyond the first 60 days after delivery.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Stefan, M. and C. Cillian (2022). "Segmental resection versus local excision of rectum endometrial deposits: a systematic review and meta-analysis."
	
Stefano, S., et al. (2021). "CO2 laser and genitourinary syndrome of menopause: a systematic review."
	
Stefy, S., et al. (2021). "Vitamin B status and its impact in postmenopausal women."
	
Stehlin, F., et al. (2023). "Hypersensitivity Reactions to Paclitaxel: Premedication Enhancement to Safely Achieve Treatment Completion." Journal of Allergy and Clinical Immunology 151(2 Supplement): AB334.
	Rationale: Management of patients with immediate hypersensitivity reactions (iHSR) to paclitaxel is debated and several management approaches have been proposed including desensitization. Herein, we study iHSR phenotypes and the interest of premedication enhancement to achieve successful treatment completion. Method(s): A 6- year retrospective descriptive chart review was conducted for patients treated with paclitaxel for gynecological cancers at MUHC from January 1st 2016 to May 30th 2022. Patients included received at least one cycle of paclitaxel and experienced iHSR. Reaction phenotypes, reaction severity, enhancement in premedication regimens and successful treatment completion rates were analyzed. Result(s): Out of 425 patients treated with paclitaxel, 124 (29.2%) experienced an iHSR. 101 of 143 iHSRs (70.6%) were grade 2 on Brown Scale and 2 (1.4%) were grade 3. Sixty-six patients (46.1%) had type I reactions, compared to 23 (16.1%) and 54 (37.7%) with infusion/cytokine reaction and mixed reaction respectively. Seventeen (11.8%) met the anaphylaxis criteria according to Brighton scale (level 2). Out of 124 patients with premedication enhancement (by adding antihistamines, leukotrienes blockers and/or corticosteroids as well as slowing the infusion rate), 104 (83.8%) completed their treatment. The 2 patients (100%) with Brown grade 3 reaction completed their treatment with premedication adjustment, similarly for 12 of 13 patients (93%) with level 2 Brighton anaphylaxis. Conclusion(s): Premedication enhancement is an effective and simple way to safely achieve paclitaxel treatment completion in patients who experienced mild, moderate, and severe iHSR. Safety and efficiency in severe iHSR has to be confirmed with larger populations.Copyright © 2022

Stein, A., et al. (2019). "The Role of Physical Therapy in Sexual Health in Men and Women: Evaluation and Treatment." Sexual Medicine Reviews 7(1): 46-56.
	Introduction: Many conditions of pelvic and sexual dysfunction can be addressed successfully through pelvic floor physical therapy (PFPT) through various manual therapy techniques, neuromuscular reeducation, and behavioral modifications. The field of pelvic rehabilitation, including sexual health, continues to advance to modify these techniques according to a biopsychosocial model.; Aim: To provide an update on peer-reviewed literature on the role of PFPT in the evaluation and treatment of pelvic and sexual dysfunctions in men and women owing to the overactive and the underactive pelvic floor.; Methods: A literature review to provide an update on the advances of a neuromusculoskeletal approach to PFPT evaluation and treatment.; Main Outcome Measure: The use and advancement of PFPT methods can help in successfully treating pelvic and sexual disorders.; Results: PFPT for pelvic muscle overactivity and underactivity has been proven to be a successful option for pelvic and sexual dysfunction. Understanding the role of the organs, nerves, fascia, and musculoskeletal system in the abdomino-pelvic and lumbo-sacro-hip region and how pelvic floor physical therapists can effectively evaluate and treat pelvic and sexual health. It is important for the treating practitioner to know when to refer to PFPT.; Conclusion: Neuromusculoskeletal causes of pelvic floor disorders affect a substantial proportion of men, women, and children and PFPT is a successful and non-invasive option. Pelvic floor examination by healthcare practitioners is essential in identifying when to refer to PFPT. Use of a biopsychosocial model is important for the overall well-being of each patient. Further research is needed. Stein A, Sauder SK, Reale J. The role of physical therapy in sexual health in men and women: Evaluation and treatment. Sex Med Rev 2019;7:46-56. (Published by Elsevier Inc.)

Steinberg Jecca, R., et al. (2022). "Early Discontinuation, Results Reporting, and Publication of Gynecology Clinical Trials From 2007 to 2020." Obstetrics and Gynecology 139(5): 821-831.
	Objective: To characterize gynecology clinical trials over time, compare gynecology subspecialties, and analyze factors associated with early discontinuation, results reporting, and publication.; Methods: We conducted a cross-sectional analysis of all gynecology trials registered on ClinicalTrials.gov between 2007 and 2020 and their resulting publications. Trials were analyzed with descriptive, multivariable logistic, and Cox regression analyses. Primary exposure variables were trial funding and subspecialty. The three primary outcomes included early discontinuation, results reporting to ClinicalTrials.gov, and publication in a peer-reviewed journal indexed on PubMed.; Results: Of 223,690 trials registered on ClinicalTrials.gov between October 2007 and March 2020, only 3.7% focused on gynecology (n=8,174, approximately 3,759,086 participants). Subspecialties included reproductive endocrinology and infertility (n=1,428, 17.5%), gynecologic oncology (n=2,063, 25.2%), urogynecology (n=1,118, 13.7%), family planning (n=648, 7.9%), and other benign gynecology (n=2,917, 35.7%). Only 42.0% of completed trials disseminated results through results reporting and publication. Of all funding types, industry-funded trials were the most likely to be discontinued early (P<.001). Academic-funded trials were the least likely to report results (adjusted odds ratio [aOR] 0.38, 95% CI 0.30-0.50) but the most likely to publish (aOR 1.62, 95% CI 1.24-2.12). The number of reproductive endocrinology and infertility trials increased the most of any subspecialty between 2007 and 2020 (6.4% growth rate). Reproductive endocrinology and infertility and family planning trials were the most likely to be stopped early (reproductive endocrinology and infertility: adjusted hazard ratio [aHR] 2.08, 95% CI 1.59-2.71; family planning: aHR 1.55 95% CI 1.06-2.25). When completed, reproductive endocrinology and infertility trials were the least likely to report results (aOR 0.58, 95% CI 0.38-0.88). No significant differences were seen between subspecialties with respect to publication.; Conclusion: Gynecology trials comprise only 3.7% of all clinical trials. The paucity of gynecology clinical trials aligns with decades of female underrepresentation in research. When completed, gynecology trials have poor dissemination. Our findings raise concern about bias in the performance, reporting, and publication of gynecology clinical trials.; Competing Interests: Financial Disclosure Magdy P. Milad disclosed that they have served on the advisory board for Myovant Baxter Doximity, received grant money for the Empower endometriosis study (Storz research grant), and they also do medicolegal work. The other authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Stelten, S., et al. (2020). "Rationale and study protocol of the Physical Activity and Dietary intervention in women with OVArian cancer (PADOVA) study: a randomised controlled trial to evaluate effectiveness of a tailored exercise and dietary intervention on body composition, physical function and fatigue in women with ovarian cancer undergoing chemotherapy." BMJ Open 10(11): e036854.
	Introduction: As a consequence of ovarian cancer and its treatment, many women with ovarian cancer have to deal with reduced physical function, fatigue, and loss of weight and/or muscle mass, compromising quality of life. Exercise and dietary interventions can positively influence body composition, physical fitness and function, and fatigue in patients with cancer. However, there are no data from randomised controlled trials on the effectiveness of exercise and dietary interventions in patients with ovarian cancer. Due to a complex disease trajectory, a relatively poor survival and distinct disease-induced and treatment-induced side effects, it is unclear whether exercise and dietary interventions that were shown to be feasible and effective in other types of cancer produce comparable results in patients with ovarian cancer. The aim of this article is to present the design of the multicentre randomised controlled Physical Activity and Dietary intervention in OVArian cancer trial and to describe how the exercise and dietary intervention is tailored to specific comorbidities and disease-induced and treatment-induced adverse effects in patients with ovarian cancer.; Methods and Analysis: Adult women with primary epithelial ovarian cancer who are scheduled to undergo first-line (neo)adjuvant chemotherapy (n=122) are randomly allocated to a combined exercise and dietary intervention or a usual care control group during chemotherapy. Primary outcomes are body composition, physical function and fatigue. Outcome measures will be assessed before the start of chemotherapy, 3 weeks after completion of chemotherapy and 12 weeks later. The exercise and dietary intervention was tailored to ovarian cancer-specific comorbidities and adverse effects of ovarian cancer and its treatment following the i3-S strategy.; Ethics and Dissemination: This study has been approved by the medical ethical committee of the Amsterdam UMC (reference: 018). Results of the study will be published in international peer-reviewed journals.; Trial Registration Number: Netherlands Trial Registry (NTR6300).; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Stelten, S., et al. (2022). "Association between Energy Balance-Related Factors and Clinical Outcomes in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis." Cancers 14(19).
	Background: This systematic review and meta-analysis synthesized evidence in patients with ovarian cancer at diagnosis and/or during first-line treatment on; (i) the association of body weight, body composition, diet, exercise, sedentary behavior, or physical fitness with clinical outcomes; and (ii) the effect of exercise and/or dietary interventions. Methods: Risk of bias assessments and best-evidence syntheses were completed. Meta-analyses were performed when ≥3 papers presented point estimates and variability measures of associations or effects. Results: Body mass index (BMI) at diagnosis was not significantly associated with survival. Although the following trends were not supported by the best-evidence syntheses, the meta-analyses revealed that a higher BMI was associated with a higher risk of post-surgical complications (n = 5, HR: 1.63, 95% CI: 1.06−2.51, p = 0.030), a higher muscle mass was associated with a better progression-free survival (n = 3, HR: 1.41, 95% CI: 1.04−1.91, p = 0.030) and a higher muscle density was associated with a better overall survival (n = 3, HR: 2.12, 95% CI: 1.62−2.79, p < 0.001). Muscle measures were not significantly associated with surgical or chemotherapy-related outcomes. Conclusions: The prognostic value of baseline BMI for clinical outcomes is limited, but muscle mass and density may have more prognostic potential. High-quality studies with comprehensive reporting of results are required to improve our understanding of the prognostic value of body composition measures for clinical outcomes. Systematic review registration number: PROSPERO identifier CRD42020163058.

Stelwagen, J., et al. (2021). "Current treatment strategies and future directions for extrapulmonary neuroendocrine carcinomas a review." JAMA Oncology 7(5): 759-770.
	
Stener-Victorin, E., et al. (2019). "Acupuncture or metformin to improve insulin resistance in women with polycystic ovary syndrome: study protocol of a combined multinational cross sectional case-control study and a randomised controlled trial." BMJ Open 9(1): e024733.
	Introduction: Polycystic ovary syndrome (PCOS) is linked to hyperinsulinemia and insulin resistance with dysfunctional glucose metabolism. Pilot studies suggests that acupuncture treatment with combined manual and low-frequency electrical stimulation (electroacupuncture (EA)) of the needles decrease circulating glycated haemoglobulin (HbA1c) and homeostatic model assessment-insulin resistance. Therefore, we here aim to investigate if acupuncture treatment or metformin together with lifestyle or lifestyle management alone improves insulin sensitivity and related symptoms in overweight/obese women with PCOS.; Methods and Analysis: This is a two-centre multinational (Sweden and China), cross-sectional case-control study combined with an open-labelled randomised controlled trial (RCT). Participants are randomised to one of three groups: (1) EA 2-3 times/week during 4 months+lifestyle management; (2) metformin, 500 mg, three/day during 4 months+lifestyle management; or (3) lifestyle management alone. The primary outcome measure in the RCT is changes in HbA1C. A total of 123 obese overweight women with PCOS will be enrolled and randomised into one of the three groups with a target power of at least 80% and 5% significance level based on two-sided tests.; Ethics and Dissemination: The study has been approved by the Regional Ethical Review Board of Stockholm and of Peking University Third Hospital, China. Primary outcome data of the RCT will be published in a relevant journal together with supporting secondary outcome measurements. Further, outcome measurements will be published in separate papers as well as case-control data.; Expected Results: We anticipate that EA and metformin, both with lifestyle management, are equally effective and superior to lifestyle management alone for improvement of glycaemic control.; Trial Registration Numbers: NCT02647827 and EudraCT2015-004250-18.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Stenson, A. L., et al. (2021). "Comparing Vestibule Examination Techniques: Light Touch, Serial Forces, and the Lidocaine Test." Journal of Lower Genital Tract Disease 25(3): 236-242.
	OBJECTIVE: The purpose of this study was to compare techniques and pain scales that assess tenderness in the vulvar vestibule in provoked vestibulodynia, using the cotton swab test and a vulvalgesiometer, and assess topical lidocaine solution with each. MATERIALS AND METHODS: This randomized study at a specialty vulvar clinic evaluated tender vestibules of reproductive-aged women with vestibulodynia using light rolling cotton swab touch at 6 sites and evaluated the vulvalgesiometer at 2 sites, randomizing the order of the initial tool. Participants reported pain using the Numerical Rating Scale 0-10 and the Verbal Pain Scale 0-3. With the vulvalgesiometer, the pain tolerance threshold was measured using forces of 10, 25, 50, 100, 200, and 300 g. After both initial tests, lidocaine 4% topical solution was applied for 3 minutes, and the swab test and vulvalgesiometer were repeated in the order initially performed, constituting the lidocaine test. Data analysis used t tests, Fisher exact tests, Wilcoxon signed rank tests, and Spearman rank correlation. RESULTS: Sixteen patients completed the study, 8 starting with each instrument. Light swab touch evoked significant pain, and lidocaine reduced pain to zero or mild levels. The pain threshold was 25 g, and only 38% could tolerate testing past 100 g without lidocaine. The Verbal Pain Scale correlated well with the Numerical Rating Scale. CONCLUSIONS: Light rolling cotton swab touch using the 4-item verbal scale can map vestibulodynia tenderness that can be extinguished by lidocaine, consistent with distinguishing a mucosal condition. Forces by vulvalgesiometer of greater than 100-200 g may evoke pain other than mucosal allodynia.

Stepan, F., et al. (2022). "Vitamin E in patients with menopause symptoms – a protocol of systematic review."
	
Stepan, F., et al. (2022). "Estrogen receptors and their influence on lyomyoma – a protocol of systematic review."
	
Stephan, A.-J., et al. (2022). "Healthcare Costs and Resource Use Associated With Cervical Intraepithelial Neoplasia and Cervical Conization: A Retrospective Study of German Statutory Health Insurance Claims Data." Journal of health economics and outcomes research 9(1): 128-139.
	Background: Cervical intraepithelial neoplasia (CIN) can be a consequence of human papillomavirus (HPV) infection. High-grade CIN (CIN2/CIN3) may develop from persistent HPV infection and progress to cervical cancer if left untreated. Management of CIN includes conservative surveillance or ablation and excision by conization. Internationally, CIN and its treatment generate a considerable economic burden, but no current data regarding costs and resource use from the perspective of the German statutory health insurance exist. Objectives: The aim of this study was to explore the health economic burden in women with CIN diagnoses who either underwent cervical conization or were managed conservatively. Methods: We conducted a retrospective claims data analysis using the InGef Research Database from 2013 to 2018. Healthcare costs and resource utilization in a 24-month observation period (1:1:1 matching) were compared in 18- to 45-year-old women with CIN (1-3) who underwent a conization procedure (study cohort 1) and in women with CIN (1-3) who did not undergo conization (study cohort 2) to women with neither CIN nor conization (control group). Results: For each group, 2749 women were identified. Mean total healthcare costs after 24 months were higher in study cohort 1 (€4446, P <.01) and study cohort 2 (€3754, P =.09) compared with the control group (€3426). Comparing study cohort 1 and 2 to controls, mean differences were highest in age groups 41-45 years (cohort 1: €5115 vs €3354, P <.01; cohort 2: €4152 vs €3354, P =.14). Significantly more women were hospitalized at least once in study cohort 1 (57.46%, P <.01) and study cohort 2 (38.74%, P <.01) compared with the control group (31.14%). Frequency of outpatient physician visits was significantly higher in both study cohorts (43.23 visits, P<.01 and 38.60 visits, P <.01) compared with the control group (32.07 visits). Conclusion: Our results revealed 30% and 10% increased total healthcare costs in women with CIN undergoing invasive treatment (study cohort 1) and conservative management (study cohort 2), respectively, compared with a control group of women with no CIN in a 2-year follow-up period.

Stephanie, K. and R. Brigitte (2021). "Various mentalizing concepts in mothers with postpartum depression, comorbid anxiety, and personality disorders." Infant mental health journal 42(4): 488-501.
	BACKGROUND: Mentalization is defined as the human capacity to reflect upon one's own or others' behaviors in terms of underlying mental states and intentions. Several concepts of mentalizing exist, which differ in content, assessment, and clinical prediction. AIMS: The present study examines the relationship between the three main concepts of mentalizing, namely, reflective functioning (RF), parental reflective functioning (PRF), and Mind-Mindedness (MM), in mothers with postpartum depression. It was hypothesized that mentalizing concepts differ in their convergent and divergent variance, as well as their clinical validity regarding comorbid anxiety and personality disorders (PDs). METHOD: Fifty clinically referred mothers with postpartum depression and infants aged 3-10 months were examined by means of the Reflective Functioning Scale, Parental Reflective Functioning Questionnaire, and Mind-Mindedness Coding-System. RESULTS: No significant associations were found between RF and PRF, or between PRF and MM; higher RF was associated with more MM-nonattuned mind-related comments. Increased depression and anxiety were linked to lower PRF in terms of higher PRF-prementalizing. Lower RF, but not PRF, was associated with comorbid PDs. Specifically, obsessive-compulsive PD was associated to considerably fewer MM-nonattuned mind-related comments. CONCLUSION: Distinct concepts of mentalizing represent divergent competencies, differentially linked to maternal postpartum psychopathology.

Stephens-Shields Alisa, J., et al. (2023). "Clinically Important Differences for Pain and Urinary Symptoms in Urological Chronic Pelvic Pain Syndrome: A MAPP Network Study." The Journal of Urology 209(6): 1132-1140.
	Purpose: Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urological chronic pelvic pain syndrome, has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences for 2 primary symptom measures, pelvic pain severity and urinary symptom severity, and evaluate subgroup differences.; Materials and Methods: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with urological chronic pelvic pain syndrome. We defined clinically important differences by associating changes in pelvic pain severity and urinary symptom severity over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated clinically important differences for absolute and percent change and examined differences in clinically important differences by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity.; Results: An absolute change of -4 was clinically important in pelvic pain severity among all patients, but clinically important difference estimates differed by pain type, presence of Hunner lesions, and baseline severity. Pelvic pain severity clinically important difference estimates for percent change were more consistent across subgroups and ranged from 30% to 57%. The absolute change urinary symptom severity clinically important difference was -3 for female participants and -2 for male participants with chronic prostatitis/chronic pelvic pain syndrome only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated clinically important differences had lower accuracy among participants with low baseline symptoms.; Conclusions: A reduction of 30%-50% in pelvic pain severity is a clinically meaningful endpoint for future therapeutic trials in urological chronic pelvic pain syndrome. Urinary symptom severity clinically important differences are more appropriately defined separately for male and female participants.

Stern Judy, E., et al. (2022). "Assisted reproductive technology treatment increases obstetric and neonatal risks over that of the underlying infertility diagnosis." Fertility and Sterility 117(6): 1223-1234.
	Objective: To determine whether assisted reproductive technology (ART) treatment adds obstetric and neonatal risks over and above that of underlying infertility-related diagnoses.; Design: Retrospective study of linked ART, birth certificate, hospital discharge data, and outpatient insurance claims data in Massachusetts (2013-2017).; Setting: Database.; Patient(s): Singleton deliveries in women with and without diagnoses of tubal disease, polycystic ovarian syndrome (PCOS), other ovulatory conditions, or endometriosis, identified from the insurance claims and ART data.; Intervention(s): None.; Main Outcome Measure(s): ART and non-ART pregnancy and delivery outcomes were compared with each other and with women with no history of infertility or usage of fertility treatment (fertile group). Generalizing estimating equations with Poisson distribution and exchangeable correlation structure were used to obtain adjusted relative risk ratios (aRRs) and 95% confidence intervals (CIs).; Result(s): Infertility-related diagnoses significantly increased the risks of pregnancy hypertension (PCOS: aRR, 1.13, 95% CI 1.00-1.27), preeclampsia/eclampsia (tubal: aRR 1.28, 95% CI 1.02-1.61; PCOS: aRR 1.23, 95% CI 1.06-1.43; other ovulatory: aRR 1.11, 95% CI 1.02-1.20), gestational diabetes (tubal: aRR 1.28, 95% CI 1.08-1.50; PCOS: aRR 1.58, 95% CI 1.42-1.75; other ovulatory: aRR 1.19, 95% CI 1.12-1.26), and placental problems (tubal aRR 1.47, 95% CI 1.11-1.94), as well as low birthweight and prematurity, compared with deliveries from the fertile group. Within each diagnosis, the use of ART consistently increased the risk of placental problems (aRR 1.49-2.86) but varied for other conditions.; Conclusion(s): Our study demonstrated that compared with the fertile group, risk was elevated in pregnancies and deliveries from women with tubal, PCOS, other ovulatory, and endometriosis diagnoses who did/did not undergo ART treatment. Placental abnormalities were particularly elevated in ART compared to non-ART deliveries having the same diagnosis. (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Stevens, M. J., et al. (2023). "Safety and efficacy of single insertion accelerated MR-image guided brachytherapy following chemo-radiation in locally advanced cervix cancer: modifying our EMBRACE during the COVID pandemic." Radiation Oncology 18(1): 54.
	Background: Utero-vaginal brachytherapy (BT) is an irreplaceable care component for the curative treatment of locally advanced cervix cancer (LACC). Magnetic Resonance Imaging (MRI)-image guided adaptive BT (IGABT) using the GYN-GEC-ESTRO EMBRACE guidelines is the international care standard. Usually following chemo-radiation therapy (CRT), IGABT has high proven utility in LACC but requires significant health system resources. Timely access was disrupted by the COVID-19 pandemic which challenged us to re-design our established IGABT care pathway. Method(s): From April 2020 consecutive patients with LACC were enrolled after CRT in a single arm exploratory non-inferiority study of a modified IGABT (mIGABT) protocol. This delivered an iso-effective IGABT dose (39.3 Gy: EQD2: alpha/beta10Gy concept) over a 24-h period during a single overnight hospitalisation. Result(s): Fourteen LACC patients received mIGABT from April 2020 to March 2022. Median age was 62.5 years (37-82 years). LACC histology was primary squamous (9/14) or adeno-carcinoma (5/14). International Federation of Gynaecology and Obstetrics (FIGO) 2018 stages ranged from IB1/2 (N = 3), IIA1/IIB (5), IIIB (2), IIIC1/2 (4) with mean +/- standard deviation (SD) gross tumour volume-at-diagnosis (GTV_D) of 37.7 cc +/- 71.6 cc. All patients achieved complete metabolic, clinical, and cytologic cancer response with CRT and IGABT. High-risk HPV was cleared by 6-months. Complete MRI-defined cancer response before mIGABT (GTV_Fx1) was seen in 77% of cases (10/13). Only two women developed metastatic disease and one died at 12-months; 13 patients were alive without cancer at mean 20.3 +/- 7.2 months follow-up. Actuarial 2-year overall survival was 93%. Compared with our pre-COVID IGABT program, overall mIGABT cost-saving in this cohort was USD 22,866. Prescribed dose covered at least 90% (D90) of the entire cervix and any residual cancer at time of BT (HRCTV_D90: high-risk clinical target volume) with 3-fractions of 8.5 Gy delivered over 24-h (22.8 +/- 1.7 h). Total treatment time including CRT was 38 days. The mIGABT schedule was well tolerated and the entire cohort met EMBRACE recommended (EQD2: alpha/beta10Gy) combined HRCTV_D90 coverage of 87.5 +/- 3.7 Gy. Similarly, organ-at-risk (OAR) median: interquartile range D2cc constraints (EQD2: alpha/beta3Gy) were EMBRACE compliant: bladder (65.9 Gy: 58.4-72.5 Gy), rectum (59.1 Gy: 55.7-61.8 Gy), and sigmoid colon (54.6 Gy: 50.3-58.9 Gy). ICRU recto-vaginal point dose was significantly higher (75.7 Gy) in our only case of severe (G4) pelvic toxicity. Conclusion(s): This study demonstrated the utility of mIGABT and VMAT CRT in a small cohort with LACC. Loco-regional control was achieved in all cases with minimal emergent toxicity. Single insertion mIGABT was logistically efficient, cost-saving, and patient-centric during the COVID-19 pandemic.Copyright © 2023, The Author(s).

Stewart Anne, L. and L. Payne Jennifer (2023). "Perinatal Depression: A Review and an Update." The Psychiatric clinics of North America 46(3): 447-461.
	Perinatal depression is a common psychiatric condition that has negative effects on pregnancy and infant outcomes. Screening for the condition is relatively easy and should be done routinely in all medical care of the pregnant and postpartum woman and her infant. The risk-benefit analysis favors the use of antidepressant medications during pregnancy and lactation compared with the risk of untreated maternal depression. Other, nonpharmacological treatments will be discussed as well as new treatments, including a new class of medications that act on the inhibitory GABAergic neurotransmitter system. (Copyright © 2023 Elsevier Inc. All rights reserved.)

Stewart, C. A., et al. (2021). "Outcomes of Prophylactic Mid-Urethral Sling at the Time of Robotic Sacrocolpopexy." Urology 150: 130-133.
	OBJECTIVE: To compare outcomes of patients who underwent robotic sacrocolpopexy (RSC) with and without concomitant mid-urethral sling (MUS) placement for prophylaxis or treatment of preoperative stress urinary incontinence (SUI) METHODS: We performed a retrospective review of all patients without prior incontinence procedures who underwent RSC with or without MUS placement by 3 surgeons (JA, LA, KE) at a single institution from 2012 to 2017 for treatment of pelvic organ prolapse. Patients had a MUS placed for either documented SUI or prophylaxis of SUI. We compared patient characteristics, operative details, postoperative outcomes, and complications between the groups. RESULTS: A total of 134 patients were identified. 58 (43%) had a MUS placed for documented SUI, 43 (32%) had prophylactic MUS, and 33 (25%) did not have a MUS placed. There were no differences in baseline characteristics between the 3 groups. Patients who did not have a MUS placed had less estimated blood loss (76.4 vs 63.8 vs 36.9 mL, P = .018) but no difference in operative time (P = .408), length of stay (P = .427), or postoperative urinary retention (P = .988). A total of 4 (7%) patients who had a MUS placed for SUI had persistent SUI postoperatively. There were 2 (5%) patients who had a MUS placed prophylactically and 4 (12%) patients who did not have a MUS that developed de novo SUI. CONCLUSION: In this series, we demonstrate the safety and efficacy of prophylactic MUS placement at the time of RSC. Randomized studies evaluating concomitant prophylactic sling at time of robotic sacrocolpopexy could further guide preoperative patient counseling and decision-making.

Stewart, E. A., et al. (2022). "Relugolix Combination Therapy Improves Uterine Fibroid Symptoms Independent of Fibroid Location over 24 Weeks." Journal of Minimally Invasive Gynecology 29(11 Supplement): S1.
	Study Objective: To evaluate the impact of fibroid location (submucosal, intramural, or subserosal) on treatment outcomes with relugolix combination therapy (Relugolix-CT) in women with uterine fibroid (UF)-associated heavy menstrual bleeding (HMB) in the LIBERTY 1 (L1) and LIBERTY 2 (L2) studies. Design(s): L1 and L2 were replicate, Phase 3, double-blind, 24-week trials. Setting(s): 80 (L1) and 99 (L2) research centers globally. Patients or Participants: Premenopausal women (age 18-50 years) with diagnosed UF (confirmed on ultrasonography) and HMB (assessed by the alkaline hematin method). Intervention(s): Participants were randomized to once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) or placebo for 24 weeks. Measurements and Main Results: Fibroid location was investigator-defined using ultrasound; FIGO type 0/1 fibroids were excluded. Menstrual blood loss (MBL) volume was measured by alkaline hematin method (responders: MBL volume <80mL and >=50% reduction from baseline over last 35 days of treatment). Pain and other UF-associated symptoms were evaluated using the Numerical Rating Scale and Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (Symptom Severity scale) in this post-hoc analysis. Pooled L1 and L2 data were used. In the Relugolix-CT (N=253) and placebo (N=256) groups, fibroid location was categorized as subserous (N=50 and N=58), intramural (N=115 and N=130), submucosal (N=46 and N=43) or "other/unknown" (N=119 and N=106). Overall, 136 women had >1 type of fibroid and were therefore included in >1 subgroup. Baseline characteristics, including MBL volume, pain and quality of life scores, were similar between subgroups. For each fibroid subgroup, respectively, women randomized to Relugolix-CT had comparable responder rates: 76.0%, 79.1%, 80.4%, and 65.6% at Week 24, which were higher than with placebo: 24.1%, 16.2%, 14.0%, and 16.0% (all nominal p<0.0001). Across all subgroups, Relugolix-CT resulted in significant reductions in MBL volume, UF-associated pain and Symptom Severity versus placebo. Conclusion(s): Relugolix-CT improved HMB and other UF-associated symptoms through 24 weeks independent of fibroid location.Copyright © 2022

Stewart, E. A., et al. (2022). "Effect of the Oral GnRH Antagonist Linzagolix on Uterine Fibroid-Related Severe Anemia." Obstetrics and Gynecology 139(SUPPL 1): 31S.
	INTRODUCTION: Iron-deficiency anemia is common in women with uterine fibroid (UF)-related heavy menstrual bleeding. Severe anemia is defined as hemoglobin (Hb) levels <10g/dL. The effect of linzagolix, an oral GnRH antagonist, on UF-related severe anemia was assessed in two Phase 3 trials. METHOD(S): PRIMROSE 1 and 2 are randomized, double-blind, placebo-controlled Phase 3 trials investigating the efficacy and safety of linzagolix 100 mg and 200 mg once daily, with or without hormonal add-back therapy (ABT) in the treatment of UF. Subjects were considered responders if an increase of >=2g/dL from baseline was achieved. Patients with severe anemia were given iron supplements until they reached the Hb levels >12g/dL. RESULT(S): In PRIMROSE 1, of 165 subjects with severe anemia, 57.9%, 61.5%, 82.1% and 65.2% of patients were responders at 24 weeks, in the respective treatment groups (100 mg, 100 mg+ABT, 200 mg and 200 mg+ABT), compared to 50% in the placebo group. In PRIMROSE 2, of 93 patients with severe anemia, 62.5%, 75%, 60% and 73.7%, respectively, were responders, compared to 46.2% for placebo. Given the small sample sizes, statistical significance was not reached. Improvements were maintained at week 52: in PRIMROSE 1, 69.2%, 62.5%, 81.3% and 75% of patients were responders in the respective treatment groups, compared to 40% in placebo, in PRIMROSE 2, 66.7%, 100%, 80%, 87% were responders, respectively. CONCLUSION(S): High and low doses of linzagolix improved Hb levels in patients with UF suffering from severe anemia.

Stewart Elizabeth, A., et al. (2022). "Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids." Journal of women's health (2002) 31(5): 698-705.
	Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.

Stewart, K., et al. (2022). "Fractional CO 2 laser treatment as adjunctive therapy to topical steroids for managing vulvar lichen sclerosus." Lasers in surgery and medicine 54(1): 138-151.
	Objectives: Uncontrolled vulvar lichen sclerosus (VLS) is often associated with distressful symptoms of genital itch, irritation, and pain and can lead to a pathological process including anatomical changes, scarring, and an elevated risk of cancer in the genital area. First-line topical corticosteroid as monotherapy is frequently not adequate to fully suppress disease activity and control symptoms. This study evaluated the efficacy of fractional CO 2 laser treatments as adjunctive therapy where recalcitrant VLS had been improved, but not adequately controlled, with topical corticosteroid treatment. Outcomes were evaluated up to 12 months after a series of CO 2 laser treatments delivered via a fractional handpiece.; Materials and Methods: Women with a diagnosis of VLS supported by histologic findings on biopsy and/or clinical signs on physical examination received up to five monthly laser treatments. Subjects maintained existing topical corticosteroid and any exogenous hormone treatment during the study. Investigators assessed severity (0 = not present, 1 = mild, 2 = moderate, or 3 = severe) of clinical signs and architectural changes present before adjunctive study interventions and at follow-up visits. Subjects reported the presence of clinical symptoms and impact on quality of life on 4- or 5-point Likert scales. The validated Female Sexual Function Index (FSFI) was used to assess changes in sexual function. Four subjects were biopsied before adjunctive laser treatment and at follow-up.; Results: Twelve females, 11 postmenopausal, with a mean age of 57 ± 10 years received three to five monthly CO 2 laser treatments. Significant improvement in all prominent clinical signs and architectural changes were reported at the 3- and 6-month follow-ups after the treatment series. Significant improvement was maintained at the 12-month follow-up, with 89% of subjects showing at least one-point improvement in elasticity compared to baseline; 86% in lichenification; 88% in sclerosis; and 80% in whitening and parchment-like skin. Labial fusion and the extent of disease improved in 50% of patients. Ulcerations present in three subjects at baseline resolved after treatment. Subjects reported 86% improvement in dyspareunia and 83% in skin tearing. Quality of life improved significantly after treatment (p < 0.01). The 6-month follow-up FSFI showed significant improvement in sexual function compared to baseline (p < 0.05), with a mean point improvement of 4.5. Histology findings after treatment showed some positive improvement, as a decrease in dermal hyalinized zone thickness. There were no treatment complications or adverse events related to the treatment.; Conclusions: Fractional CO 2 laser treatment outcomes showed improvement in predominant clinical signs and architectural changes in VLS recalcitrant to topical corticosteroid treatment. Adjunctive laser treatment relieved symptoms and improved quality of life as well as sexual function. Fractional CO 2 laser treatment may provide an advanced treatment modality for the management of recalcitrant VLS with improved patient care and sustainable outcomes. Further study in a larger population and with CO 2 laser treatment to both vulvar tissue and the vaginal canal should be explored. (© 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Stewart, K. A., et al. (2023). "Radiofrequency Ablation of Leiomyomas." Obstetrics and Gynecology 141(6): 1063-1071.
	Radiofrequency ablation (RFA) of leiomyomas represents a significant advancement in the treatment of this common uterine condition. In the appropriately selected patient, both laparoscopic and transcervical options provide effective treatment for bleeding and bulk symptoms in a uterine-sparing manner. Compared with other minimally invasive leiomyoma treatment options, RFA procedures have comparable or favorable safety profiles, recovery timelines, and reintervention rates. Data on future fertility and pregnancy are limited, although early reports are promising.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Stewart, L. A., et al. (2021). "Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials." The Lancet 397(10280): 1183-1194.
	Background: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes. Method(s): We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299. Finding(s): Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0.78, 95% CI 0.68-0.90), 17-OHPC (five trials, 3053 women; 0.83, 0.68-1.01), and oral progesterone (two trials, 181 women; 0.60, 0.40-0.90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1.01, 95% CI 0.84-1.20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1.04, 0.92-1.18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1.59, 95% CI 1.15-2.22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC. Interpretation(s): Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence. Funding(s): Patient-Centered Outcomes Research Institute.Copyright © 2021 Elsevier Ltd

Stickler, L. G., et al. (2019). "The Impact of Nutritional Intervention on Menstrual Dysfunction in Female Athletes: a Systematic Review." SN Comprehensive Clinical Medicine 1(9): 669-676.
	Menstrual function is strongly affected by nutritional status and energy availability in female athletes, and impaired menstrual function can impact bone mineral density. Nutritional interventions have been proposed to mitigate menstrual dysfunction. The purpose of this systematic review was to assess the ability of nutritional interventions, directed at improving energy availability, to restore normal menstrual status in female athletes. PubMed, Cinahl, and SportDiscus databases were comprehensively searched. Included studies had to investigate the impact of increasing energy availability in female athletes through a nutritional intervention. The primary outcome measure of interest was menstrual status. Included studies were reviewed for methodological rigor using the American Academy of Dietetics Quality Criteria Checklist. Five studies met the inclusion criteria. Of the athletes who completed the interventions in the studies, 0-100% resumed normal menses. For those that improved, the mean length of time for return to menses ranged from 2.63 to 15.6 months. The length of the interventions (3-9 months), mean ages of the participants (17-1-22.6 years), and particular dietary intervention(s) (counseling, education, and nutritional supplementation) varied between the studies. Nutritional interventions may restore normal menses in some female athletes. Educational strategies targeted at improved eating and understanding the energy demands of sport, as well as weekly interaction with athletes should be considered.Copyright © 2019, Springer Nature Switzerland AG.

Stie, M., et al. (2022). "Efficacy of open dialogue about complementary and alternative medicine compared with standard care in improving quality of life in patients undergoing conventional oncology treatment (CAMONCO 2): Protocol for a randomised controlled trial." BMJ Open 12(4): e059960.
	Introduction Complementary and alternative medicine (CAM) has been shown to reduce symptoms and adverse effects and improve quality of life of patients undergoing conventional oncology treatment, but CAM might also cause symptoms and adverse effects such as headache and fatigue. Thus, patients need guidance towards safe and healthy use of CAM. According to published results, open dialogue about CAM (OD-CAM) between health professionals and patients as an integral part of anticancer treatment may improve patients' quality of life and well-being. Since the literature on the issue is sparse, the aim of this study is to assess the efficacy of OD-CAM integrated early in conventional oncology treatment versus standard care (SC) in patients undergoing standard anticancer treatment. Methods and analysis The study is a randomised controlled trial, being conducted at an oncology outpatient clinic in Denmark. 207 patients undergoing curative or palliative oncology treatment for breast, gynaecological, prostate, pulmonary, colorectal, anal or pancreatic cancer will be randomly assigned to SC with or without OD-CAM. A nurse specialist will facilitate the OD-CAM in one or two sessions. The primary endpoint is patient reported quality of life in relation to psychological well-being 8 weeks after enrollment. Secondary endpoints are patient reported level of depression and anxiety, top concerns, and decision regret 8, 12 and 24 weeks after enrolment, and overall survival. Ethics and dissemination According to the Committee on Health Research Ethics for Southern Denmark, ethics approval of this study is not required (S-20202000-5, 20/1019). The Region of Southern Denmark (Journal no. 20/11100) approved the storing and handling of data. Participants' informed consent will be obtained before inclusion and randomisation. The results of the study, whether positive, negative or inconclusive, will be disseminated through open-access, peer-reviewed publications, stake-holder-reporting and presentations at relevant conferences. Trial registration number NCT04299451.Copyright © 2022 Authors

Stier-Jarmer, M., et al. (2021). "Effects of kneipp therapy: A systematic review of current scientific evidence (2000 2019)." Complementary Medicine Research 28(2): 146-159.
	Introduction: The aim of this systematic review was to evaluate the available evidence on the effect of Kneipp therapy. Method(s): MEDLINE, Embase, Web of Science, Cochrane Library and CAMbase were searched for relevant articles published between 2000 and 2019. Grey literature was obtained through Google Scholar and other tools. Studies with any kind of study design that examined the effects of Kneipp therapy were included. The quality assessment was carried out using EPHPP-QAT. Result(s): 25 sources, including 14 controlled studies, were included. According to EPHPP-QAT, 3 studies were rated as "strong," 13 as "moderate" and 9 as "weak." Nine (64%) of the controlled studies reported significant improvements after Kneipp therapy in a between-group comparison in chronic venous insufficiency, hypertension, mild heart failure, menopausal complaints, and sleep disorders in different patient collectives as well as improved immune parameters in healthy subjects. Regarding depression and anxiety in breast cancer patients with climacteric complaints, quality of life in post-polio syndrome, disease-related polyneuropathic complaints and incidence of cold episodes in children, no significant group differences were found. Eleven uncontrolled studies reported improvements in allergic symptoms, dyspepsia, quality of life, heart rate variability, infections, hypertension, well-being, pain and polyneuropathic complaints. Discussion/Conclusion: Kneipp therapy seems to be beneficial for numerous symptoms in different patient groups. Future studies should pay even more attention to methodologically careful study planning (control groups, randomisation, adequate case numbers, blinding) to counteract bias.Copyright © 2021 S. Karger AG. All rights reserved.

Stifani, B. M., et al. (2022). "Reducing the harms of unsafe abortion: a systematic review of the safety, effectiveness and acceptability of harm reduction counselling for pregnant persons seeking induced abortion." BMJ Sexual and Reproductive Health 48(2): 137-145.
	Background Globally, access to safe abortion is limited. We aimed to assess the safety, effectiveness and acceptability of harm reduction counselling for abortion, which we define as the provision of information about safe abortion methods to pregnant persons seeking abortion. Methods We searched PubMed, EMBASE, ClinicalTrials.gov, Cochrane, Global Index Medicus and the grey literature up to October 2021. We included studies in which healthcare providers gave pregnant persons information on safe use of abortifacient medications without providing the actual medications. We conducted a descriptive summary of results and a risk of bias assessment using the ROBINS-I tool. Our primary outcome was the proportion of pregnant persons who used misoprostol to induce abortion rather than other methods among those who received harm reduction counselling. Results We included four observational studies with a total of 4002 participants. Most pregnant persons who received harm reduction counselling induced abortion using misoprostol (79%-100%). Serious complication rates were low (0%-1%). Uterine aspiration rates were not always reported but were in the range of 6%-22%. Patient satisfaction with the harm reduction intervention was high (85%-98%) where reported. We rated the risk of bias for all studies as high due to a lack of comparison groups and high lost to follow-up rates. Discussion Based on a synthesis of four studies with serious methodological limitations, most recipients of harm reduction counselling use misoprostol for abortion, have low complication rates, and are satisfied with the intervention. More research is needed to determine abortionCopyright © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Stokes, W., et al. (2022). "Autonomic response to a stressor in postmenopausal females with vasomotor symptoms." Clinical Autonomic Research 32(5): 339.
	Introduction: Vasomotor symptoms (VMS, hot flashes and night sweats) associated with menopause are linked to cardiovascular disease (CVD) risk, and 70% of females experience VMS. Hypertension is a major contributor to CVD and stressors, such as the cold pressor test (CPT), can be used to predict hypertension. Postmenopausal females, compared with age-matched males, demonstrate greater sympathetic reactivity to a CPT. However, it remains unknown if postmenopausal females with VMS demonstrate greater reactivity to a CPT than those without VMS. We hypothesize that blood pressure (BP) and sympathetic reactivity to CPT will be greater in females with VMS than females without VMS. Method(s): Forty-one postmenopausal females completed two study visits. Visit 1: Participants completed an informed consent and were screened for eligibility. Using the Menopause-Specific Quality of Life Questionnaire, participants were divided into VMS (n = 23) and No VMS (NVMS; n = 18) groups. Visit 2: Participants reported to the laboratory after fasting and abstaining from caffeine, exercise, and alcohol for a minimum of 12 h. Heart rate (HR, electrocardiography), BP (finger plethysmography) and muscle sympathetic nerve activity (MSNA, microneurography [VMS: n = 18; NVMS: n = 12]) were monitored during a 10-min rest and two-min CPT. Result(s): Groups were similar in age (VMS: 63 +/- 4; NVMS: 62 +/- 4 yrs), age of menopause (VMS: 51 +/- 4; NVMS: 50 +/- 5 yrs), and body mass index (VMS: 24 +/- 3; NVMS: 26 +/- 5 kg/m2) (p>0.05). While there were no group differences in baseline mean arterial pressure (MAP) (VMS: 95 +/- 8; NVMS: 95 +/- 14 mmHg; p = 0.83) or MSNA burst incidence (VMS: 55 +/- 17; NVMS: 51 +/- 16 bursts/ 100 hb; p = 0.48), HR was similar at baseline (VMS 55 +/- 7; NVMS 59 +/- 8 bpm, p = 0.08 bpm), but was overall attenuated throughout the CPT in the VMS group compared with the NVMS group (group effect, p = 0.04). Further, MAP (group 9 time, p = 0.26) and MSNA burst incidence (group 9 time, p = 0.86) increased similarly during the CPT. Conclusion(s): Contrary to our hypothesis, females who experience VMS did not demonstrate greater BP and sympathetic reactivity a CPT, but did demonstrate lower HR, suggesting alternative mechanisms may be involved in the greater CVD risk in women with VMS.

Stoll, F., et al. (2021). "Randomized Study Comparing a Reusable Morcellator with a Resectoscope in the Hysteroscopic Treatment of Uterine Polyps: The RESMO Study." Journal of Minimally Invasive Gynecology 28(4): 801-810.
	STUDY OBJECTIVE: To compare a reusable hysteroscopic morcellator and standard resectoscopes in the hysteroscopic management of uterine polyps. DESIGN: Single-center randomized prospective single-blind trial (resectoscope-morcellator study). SETTING: Centre Médico-chirurgical Obstétrique teaching hospital, Strasbourg University Hospitals, France. PATIENTS: All patients presenting with a single endometrial polyp of size 1 cm or larger. INTERVENTIONS: After consent, the patients were randomized into 2 groups: hysteroscopic morcellation (HM) group or standard resection (SR) group. Office-based review hysteroscopy was performed 6 weeks to 8 weeks after surgery. Primary end point: time of morcellation or resection. SECONDARY OUTCOMES: total operating time (minutes), volume of fluid used (mL), fluid deficit (mL), number of morcellator or resectoscope insertions, operator comfort (visual analog scale: 0 to 10) and quality of vision (0 to 5), perioperative complications, completeness of resection, need to convert to another technique, pain assessment (visual analog scale), and length of hospitalization. At review hysteroscopy, we noted whether the resection or morcellation had been effective and if synechiae were present or absent. Statistical analyses followed Bayesian methods. MEASUREMENTS AND MAIN RESULTS: Ninety patients were randomized: 45 in the HM group and 45 in the SR group. The average size of polyps at hysteroscopy was 13.3 mm. Morcellation time was lower than resection time (6.1 minutes vs 9 minutes; p [HM < SR] = .996). This also applied to total operating time (12.7 minutes vs 15.6 minutes; p [HM < SR] = .985), number of device insertions (1.50 vs 6; p [HM < SR] > .999), volume of fluid used (766.9 mL vs 1118.9 mL; p [HM < SR] = .994), and fluid deficit (60.2 mL vs 169.8 mL; p [HM < SR] = .989). Operator comfort was better in the HM group (8.4 vs 7.4; p [HM > SR] = .999) as was visualization (4 vs 3.7; p [HM > SR] = .911, highly probable). Operative complications were higher in the SR group (5 vs 0; p [HM < SR] = .989]. One patient in the SR group died after surgery owing to an anesthetic complication (anaphylactic shock complicated by pulmonary embolism). No differences were noted between the groups for pain assessment, length of hospitalization, and outcome on review hysteroscopy. CONCLUSION: The reusable morcellator is quicker, uses less fluid with less deficit and fewer introductory maneuvers, and offers better comfort and visualization than the resectoscope while being as effective for the hysteroscopic treatment of uterine polyps.

Stolzle, A. C., et al. (2023). "SINGLE-INCISION MINISLINGS IN 2022: A META ANALYSIS." Journal of urology 209(Supplement 4): e514.
	INTRODUCTION AND OBJECTIVE: The TVT-Secur, which comprised many of the randomized controlled trials (RCTs) in the 2017 Cochrane Review of single-incision minislings (SIMS), has since been withdrawn from the market. Our purpose is to review the emerging RCTs in which SIMS comprises at least one of the trial arms. METHOD(S): A comprehensive PubMed search was performed, and several reviewers independently assessed the quality of the studies and extracted data. Study exclusion criteria included: abstract only, non-English language publication, minimum follow-up <6 months, and TVT-Secur as the sole other trial arm. A meta-analysis of surgical outcomes and adverse postoperative sequelae was performed. RESULT(S): Literature search yielded 31 unique data sets (research groups) and 43 RCTs. SIMS comprising at least one arm included: Ajust, Altis, Contasure Needleless, EFA, MiniArc, Ophira, TFS, and TVT-Abbrevo. While all studies were randomized, there was significant variation in study design, allocation concealment, blinding of outcome assessment, and handling of incomplete data sets. There was also significant variation in inclusion/exclusion criteria, outcome criteria, and adverse event reporting. In all, 2844 women had a SIMS in at least one study arm. Six studies either had a combination of two SIMS or two MUS in a trial arm, or two separate SIMS individually compared to one MUS. Objective and subjective outcomes stratified by length of follow-up and comparison device are summarized in the Table 1. Only one study reported outcomes at >48 months. Most of the comparisons were SIMS vs. transobturator midurethral slings (MUS), with only four data sets comparing SIMS and retropubic MUS. Overall, SIMS were non inferior to other MUS procedures and no one SIMS was associated with significantly better outcomes. Rates of de novo urgency and urgency incontinence, long-term pain, vaginal mesh exposure, and repeat surgery were low and were not significantly different between groups. CONCLUSION(S): Short- and medium-term results from RCTs suggest that SIMS are safe and non-inferior to other MUS. The majority of the comparisons are between SIMS and transobturator MUS and significant variations in study design make grouping of outcomes challenging.

Stone Rebecca, H., et al. (2020). "A Systematic Review of Intravaginal Diazepam for the Treatment of Pelvic Floor Hypertonic Disorder." Journal of Clinical Pharmacology 60 Suppl 2: S110-S120.
	This systematic review evaluates the efficacy of intravaginal diazepam in treating chronic pelvic pain and sexual dysfunction associated with high-tone pelvic floor dysfunction. A literature search was conducted in Medline and Web of Science, including articles from the database's inception to July 2019. The search identified 126 articles, and 5 articles met study inclusion criteria: 2 observational reviews and 3 small randomized, controlled trials (RCTs) evaluating intravaginal diazepam for high-tone pelvic floor dysfunction. The 2 observational studies identified subjective reports of improvement in sexual function for a majority of women, 96% and 71%, in each study. However, there were no statistical differences between Female Sexual Function Index (FSFI) and Visual Analog Scale (VAS) scores for pain identified. One RCT found no significant changes between groups in median FSFI or VAS scores, and a second RCT found no significant changes between groups in 100-mm VAS scores. The third RCT demonstrated that compared with placebo, treatment with transcutaneous electrical nerve stimulation and intravaginal diazepam for women with vestibulodynia and high-tone pelvic floor dysfunction yielded significant differences in reduction of dyspareunia (P ≤ .05), ability to relax pelvic floor muscles after contraction (P ≤.05), and current perception threshold values at a 5-Hz stimulation related to C fibers (P < .05), but no significant changes in 10-cm VAS scores. Intravaginal diazepam may be helpful in women with a specific diagnosis of high-tone pelvic floor dysfunction, but more and larger studies are needed to confirm these potential effects. (© 2020, The American College of Clinical Pharmacology.)

Stoniute, A., et al. (2023). "Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults." Cochrane Database of Systematic Reviews(5).
	- Background Around 16% of adults have symptoms of overactive bladder (OAB; urgency with frequency and/or urge incontinence), with prevalence increasing with age. Anticholinergic drugs are commonly used to treat this condition. This is an update of a Cochrane Review first published in 2002 and last updated in 2006. Objectives To assess the effects of anticholinergic drugs compared with placebo or no treatment for treating overactive bladder syndrome in adults. Search methods We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 14 January 2020), and the reference lists of relevant articles. We updated this search on 3 May 2022, but these results have not yet been fully incorporated. Selection criteria We included randomised or quasi‐randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug alone with placebo treatment. Data collection and analysis Two review authors independently assessed eligibility and extracted data from the included studies, including an assessment of the risk of bias. We assessed the certainty of the body of evidence using the GRADE approach. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions . Main results We included 104 studies, 71 of which were new or updated for this version of the review. Although 12 studies did not report the number of participants, there were 47,106 people in the remainder of the included studies. The majority of the studies had insufficient information to allow judgement of risk of bias and we judged them to be unclear for all domains. Nine anticholinergic drugs were included in these studies: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. No studies were found that compared anticholinergic drugs to no treatment. At the end of the treatment period, anticholinergics may slightly increase condition‐specific quality of life (mean difference (MD) 4.41 lower, 95% confidence interval (CI) 5.28 lower to 3.54 lower (scale range ‐100 to 0); 12 studies, 6804 participants; low‐certainty evidence). Anticholinergics are probably better than placebo in terms of patient perception of cure or improvement (risk ratio (RR) 1.38, 95% CI 1.15 to 1.66; 9 studies, 8457 participants; moderate‐certainty evidence), and the mean number of urgency episodes per 24‐hour period (MD 0.85 lower, 95% CI 1.03 lower to 0.67 lower; 23 studies, 16,875 participants; moderate‐certainty evidence). Compared to placebo, anticholinergics may result in an increase in dry mouth adverse events (RR 3.50, 95% CI 3.26 to 3.75; 66 studies, 38,368 participants; low‐certainty evidence), and may result in an increased risk of urinary retention (RR 3.52, 95% CI 2.04 to 6.08; 17 studies, 7862 participants; low‐certainty evidence). Taking anticholinergics may be more likely to lead to participants withdrawing from the studies due to adverse events (RR 1.37, 95% CI 1.21 to 1.56; 61 studies, 36,943 participants; low‐certainty evidence). However, taking anticholinergics probably reduces the mean number of micturitions per 24‐hour period compared to placebo (MD 0.85 lower, 95% CI 0.98 lower to 0.73 lower; 30 studies, 19,395 participants; moderate‐certainty evidence). Authors' conclusions The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of a ticholiner ics are sustained during long‐term treatment or after treatment stops. Plain language summary Effectiveness of anticholinergic drugs for treating people with overactive bladder syndrome Review question We wanted to see whether a group of drugs, called anticholinergics, made a difference to adults who had an overactive bladder (OAB) syndrome when compared to a placebo (fake) treatment. We collected and analysed all relevant studies to answer this question. Background Overactive bladder syndrome is a common problem, especially as people get older. It means that you may suddenly feel the need to go to the toilet (called an 'urgency episode'), or suddenly leak a bit of urine. Overactive bladder is caused by your bladder muscle losing control unexpectedly. It is sometimes called 'irritable bladder', 'detrusor overactivity', 'urge incontinence' or 'urgency‐frequency syndrome'. Anticholinergic drugs are often given to people who have overactive bladder. They work by relaxing the muscles and can help some of the symptoms of overactive bladder, such as leakage or needing to go to the toilet at short notice. How up‐to‐date is this review? We studied evidence that was available up until 14 January 2020. We updated this search on 3 May 2022, but these results have not yet been fully incorporated into the review. Study characteristics We included 104 studies in this review. Seventy‐one of these were new or had been updated since the last time this review was published in 2006. Twelve of these studies did not report how many people were included in their research. In total across the rest of the studies, 29,682 people were given an anticholinergic drug compared to 17,424 people who were given a placebo. The smallest study was made up of 18 people while the largest had 2334 participants. Most of the studies we included in the review lasted for 12 weeks. One study investigated symptoms only in men, while nine looked at symptoms in women. The rest of the studies included both men and women. We only included studies that used anticholinergic drugs taken by mouth, and only at dosages that doctors normally prescribe to patients. Across the studies, nine different anticholinergic drugs were included: darifenacin; fesoterodine; imidafenacin; oxybutynin; propantheline; propiverine; solifenacin; tolterodine and trospium. Study funding sources Seventy studies included in this review were funded by the companies that make and sell the drugs. Key results We found that people who take an anticholinergic drug for overactive bladder may feel a positive change in their quality of life. Also, our results show that more patients will probably perceive an improvement or cure of their symptoms of overactive bladder when compared to those who take the placebo treatment. Taking an anticholinergic drug probably results in a small reduction in the number of urgency episodes and the number of times people with overactive bladder go to the toilet in one day. Twenty‐two people in every 100 given an anticholinergic drug felt they had a dry mouth as a side effect of the drug, compared to 6 in 100 taking placebo. Taking anticholinergics may therefore increase the risk of having a dry mouth. Anticholinergics may also result in an increased risk of urinary retention: fewer than 2 in every 100 people felt they were unable to completely empty their bladder after taking an anticholinergic drug in comparison to fewer than 0.5 in every 100 people after taking placebo. Authors’ conclusions We found that anticholinergic drugs could result in small but important changes to a person’s quality of life and their overactive bladder symptoms, however it is unclear if these changes can be sustained over a long period of time.

Stovall, D. (2023). "Treatment of benign uterine bleeding in morbidly obese postmenopausal women with an aromatase inhibitor." Human Reproduction 38(Supplement 1): i464-i465.
	Study question: Can morbidly obese women with postmenopausal bleeding, a benign endometrial biopsy, and no response to an oral progestin be successfully treated using an aromatase inhibitor? Summary answer: Postmenopausal uterine bleeding in morbidly obese women with benign endometrial histology and an elevated serum estrone level do respond to treated with an aromatase inhibitor. What is known already: Morbidly obese postmenopausal women who have uterine bleeding and a benign endometrial biopsy are commonly not good surgical candidates, and need good medical treatment options especially when treatment with an oral progestin has failed. The etiology for uterine bleeding in these individuals can stem from elevated estrogen production from peripheral sources. Study design, size, duration: This was a prospective, proof of concept study with no placebo control group. Ten morbidly obese postmenopausal women with elevated serum estrone levels and uterine bleeding for < eight weeks who had failed oral progestin therapy were treated with letrozole 2.5 mg/d and evaluated monthly for 3 months duration. At the first monthly follow-up visit, serum estrone levels were re-assessed. Vaginal bleeding was re-assessed at each monthly follow-up visit. Participants/materials, setting, methods: This study was performed in an outpatient setting at a private health system. Inclusion criteria included postmenopausal uterine bleeding (not spotting), age < 50, postmenopausal status (based on an FSH level of<40 mIU/mL and an estradiol > 25 pg/mL), an estrone level < 30 pg/mL, a BMI < 40 kg/m2, a benign endometrial biopsy, a normal pelvic ultrasound, and failure of progestin therapy. All women received letrozole 2.5 mg/d and were evaluated monthly. Main results and the role of chance: Ten women were enrolled in the study. Their ages ranged from 51 to 68. Their mean BMI was 50.75 kg/m2. All of the women in the study had daily vaginal bleeding for < 8 weeks that was greater than spotting, and had additional co-morbidities that made them poor surgical candidates. Serum estrone levels pre-treatment ranged from 63 pg/mL to 550 pg/mL with a mean of 216 pg/mL. After 4 weeks of treatment with letrozole, 8 women had complete cessation of their vaginal bleeding which was sustained for the complete 3 months of follow-up. The two other women in the study had significantly reduced vaginal bleeding from treatment month one to 3 based on self-reporting. Serum estrone levels after 4 weeks of treatment with letrozole dropped by an average of 71% with a range of 50% to 93%. There were no serious adverse events, and no treatment tolerability complaints. Since there was no control group for comparison, the reductions in both vaginal bleeding and serum estrone levels could be from chance alone, including regression to the mean, and not treatment related. Limitations, reasons for caution: This was a small, proof of concept study that was performed in a select population of patients. Although a very favorable outcome was obtained in our study population, a much larger study might show both a reduced success rate in regards to vaginal bleeding and some significant adverse events. Wider implications of the findings: The data from this study suggests that morbidly obese postmenopausal women with uterine bleeding and benign endometrial histology who have failed oral progestin therapy, are poor surgical candidates, and in whom IUD placement may be very difficult, may have another good treatment option.

Stover Elizabeth, H., et al. (2022). "A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma." Gynecologic Oncology Reports 40: 100974.
	Uterine serous carcinoma (USC) is an uncommon subtype of endometrial cancer with a poor prognosis. USCs have genomic alterations in the PI3K pathway. A prior phase II study of AKT inhibitor MK-2206 (an allosteric AKT inhibitor, primarily affecting AKT1 and AKT2) in endometrial cancers resulted in progression-free survival (PFS) of ≥6 months in five out of seven patients with USC. To further assess the activity of MK-2206 in USC, we designed a phase II, single-stage assessment of MK-2206 in patients with advanced or recurrent high-grade serous endometrial cancer, who had received up to two lines of prior therapy. MK-2206 (135 mg) was administered orally once per week, in continuous 28-day cycles. Fourteen patients received treatment. The most common treatment-related adverse events were diarrhea (36%), acneiform rash (36%), nausea (29%), fatigue (29%), and hyperglycemia (21%); most events were grade 1-2. One confirmed partial response was observed in a patient who was also alive and progression-free at 6 months. One additional patient was alive and progression-free at 6 months. The clinical benefit rate was 14.3% (95% CI: 1.8 to 42.8). Five patients had stable disease (35.7%) and seven had progressive disease (50%); one was unevaluable. Median PFS was 2 months (95% CI: 1.6 to 4.4) and median overall survival was 6.4 months (95% CI: 5.1 to not reached). In summary, MK-2206 had limited activity in USC, although a few patients achieved sustained progression-free intervals in this study and in the previously reported phase II trial of MK-2206. Further investigations are needed to identify features associated with response.; Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have no competing interests relevant to this study. For completeness, the following conflicts of interest disclosure is provided: A.P.M. is a full-time employee of Novartis. V.M. has participated in advisory boards for Novartis, Iteos, Eisai, Merck, Karyopharm, Clovis, and GSK. R.D. has been a consultant for Repare Therapeutics and Mersana Therapeutics, and is a founding member and has a financial interest in VOC Health. J.F.L. has received institutional funding for clinical trials from 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, and Vigeo Therapeutics; and has participated in advisory boards for AstraZeneca, Clovis, Eisai, EpsilaBio, Genentech, GSK/Tesaro, and Regeneron Pharmaceuticals. F. M.-B. has received research support from Aileron Therapeutics, Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc., and Taiho Pharmaceutical Co.,; has been a consultant for AbbVie, Aduro BioTech Inc., Alkermes, AstraZeneca, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Genentech Inc., IBM Watson, Infinity Pharmaceuticals, Jackson Laboratory, Kolon Life Science, Lengo Therapeutics, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Samsung Bioepis, Seattle Genetics Inc., Tallac Therapeutics, Tyra Biosciences, Xencor, and Zymeworks; has received honoraria from Chugai Biopharmaceuticals; and has participated in advisory boards for Black Diamond, Biovica, Eisai, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Silverback Therapeutics, Spectrum Pharmaceuticals, and Zentalis. C.A. has received institutional funding for clinical trials from Abbvie, Clovis, Genentech, and AstraZeneca; has been a consultant for Eisai/Merck, Mersana Therapeutics, Roche/Genentech, Abbvie, AstraZeneca, Merck, and Repare Therapeutics; and has served on an ad isory board for Blueprint Medicines. R.C. has received research support from AstraZeneca, Merck, Clovis, Genmab, Roche/Genentech, Janssen, Immunogen, and Genelux; and has been a consultant for AstraZeneca, GSK, Clovis, Genmab, Roche/Genentech, Janssen, Agenus, Regeneron, OncoQuest, Immunogen, Genelux, Onxerna, Onxeo, Deciphera, and Alkermes. G.B.M. has received funding for clinical trials from AstraZeneca, Genentech, GSK,and Eli Lilly; has been a consultant and/or advisory board member for Amphista, AstraZeneca, Chrysallis Biotechnology, GSK, ImmunoMET, Ionis, Lilly, PDX Pharmaceuticals, Signalchem Lifesciences, Symphogen, Tarveda, Turbine, and Zentalis Pharmaceuticals; and has a financial interest in Catena Pharmaceuticals, ImmunoMet, SignalChem, and Tarveda. L.C.C. has been a consultant for Novartis. U.A.M. has been a consultant for Merck, Novartis, and Astrazeneca; and has served on an advisory board for Symphogen. S.N.W. has received research funding from AstraZeneca, Bayer, Bio-Path, Clovis Oncology, GSK, Mereo, Novartis, OncXerna, Roche/Genentech, Zentalis; and has been a consultant for Agenus, AstraZeneca, Clovis Oncology, Eisai, ERQX, GSK, ImmunoGen, Merck, Mereo, Novartis, Pfizer, Roche/Genentech, Vincerx, and Zentalis. P.A.K. has been a consultant for Alkermes, AstraZeneca, Bayer, GSK, Merck, Pfizer, Tesaro, Mersana, Repare Therapeutics, and Kadmon. (© 2022 The Authors.)

Strandell, A. and M. Hellgren (2023). "Time to stop routine prescription of low-molecular-weight heparin to women with recurrent pregnancy loss and inherited thrombophilia." Lancet (London, England) 402(10395): 6-7.
	Competing Interests: We declare no competing interests.

Stratpharma, A. G. (2023). Silicone Gel vs. Estrogen Vaginal Cream for the Management of Genitourinary Syndrome of Menopause.
	No Results Available Device: StrataMGT|Drug: Estrace 0.01% Vaginal Cream PROM: Quality of Life|Clinical signs|Adverse Reactions|Visual pathology|PROM: Symptoms|PROM: Dyspareunia|PROM: Product Rating|PROM: Treatment Adherence Female Not Applicable 100 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Investigator)|Primary Purpose: Treatment SPAMG02 June 2024

Stratton, P., et al. (2021). "RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF BOTULINUM TOXIN FOR ENDOMETRIOSIS-RELATED CHRONIC PELVIC PAIN." Fertility and Sterility 116(3): e52.
	Objective: Women with endometriosis‐related chronic pelvic pain (endo‐CPP) often have persistent pain despite optimized hormonal management of lesions and surgery. Pelvic floor muscle spasm may contribute to pain persistence. Here, we evaluated the longitudinal efficacy of botulinum toxin (BoNT) in relieving endo‐CPP. Materials and Methods: Women (18‐55yrs) with endo‐CPP (surgically diagnosed, optimized hormonal treatment) in a randomized, double‐masked, placebo‐controlled trial received 100U onabotulinumtoxinA or placebo into pelvic floor muscles with spasm (NCT01553201). An optional open BoNT (2nd) injection was offered any time 1‐12 months after masked injection at subject request. Baseline, 1‐month, and up to 1‐year evaluation included pelvic exam for pelvic floor muscle spasm, pain rating, medication tracking, and Oswestry Disability Index. Adverse effects were recorded. Subjects rated response to injection as benefit/no benefit, percent (%) improvement and benefit duration. T‐tests, non‐parametric tests, Fisher’s exact test, logistic regression, and survival analysis compared data. Results: Of 29 randomized women, all identified pelvic floor spasm as a major focus of endo‐CPP. No subject dropped out before 1‐year follow‐up. At 1 month after masked injection, benefit was reported by 11/15 (73%) who received BoNT compared to 4/14 (29%) placebo (p=.027). BoNT led to longer‐lasting benefit (p=.023) and a greater % improvement (p=.034) compared to placebo. The number of pelvic floor muscles in spasm decreased in BoNT cohort only (p=.019). Adjusting for treatment and benefit, higher baseline disability predicted request for 2nd injection at 1‐month (p=.022). Controlling for treatment, those without benefit more often requested open BoNT at 1‐month (p=.032). Prior to 2nd injection, placebo group had more days with no benefit than BoNT group (p=.02). Women with focal pelvic pain at baseline exam had longer lasting benefit compared to those with diffuse pain (p=.02), especially in BoNT group (p=.004). In all subjects, benefit was briefer with 1st (masked) than 2nd (open) injection (p=.02), particularly in placebo cohort (p=.002). Over time, those receiving BoNT used less pain medication than placebo group (p=.037). VAS did not reflect benefit seen due to wide pain rating variability at baseline and after injection in both groups. Adverse events were mild and not serious, with no difference in incidence between groups (p=.11). Conclusions: We demonstrate pelvic floor muscle spasm as part of endo‐CPP and relief of pain/spasm from BoNT compared to placebo that persisted over time. BoNT was well tolerated and not associated with more/worse adverse events than placebo. Those with focal pelvic pain were more likely to have longer benefit. Impact Statement: Although additional research is needed, this study supports that BoNt can be used safely and effectively to treat chronic pelvic pain on women with a history of endometriosis and ongoing spasm in the pelvic floor muscles.

Strobel, L., et al. (2023). "1949P Pegylated liposomal doxorubicin (PLD) combined with trabectedin as a treatment option in uterine sarcomas." Annals of Oncology 34(Supplement 2): S1045.
	Background: Conventional use of doxorubicin as a single-agent or in combinations with other drugs in the treatment of uterine sarcomas is associated with dose-limiting toxicities. Doxorubicin plus trabectedin was shown to increase progression-free survival (PFS) at the price of higher toxicity. PLD plus trabectedin revealed to be feasible in larger phase 2 and 3 randomised studies in ovarian cancer. We hypothesise that the therapeutic index of trabectedin plus PLD could be superior to the combination with doxorubicin because of a more favourable toxicity profile. Method(s): In this retrospective single-arm study the clinical outcome was analysed in 21 patients with uterine sarcomas treated with PLD 30 mg/m2 plus trabectedin 1.1 mg/m2 every three weeks between January 2000 and April 2023 at the University Hospital in Innsbruck. Response evaluation was done every 3 cycles and every 3 months during the post-treatment follow-up. Toxicity was evaluated according to the National Cancer Institute-Common Terminology criteria, on a total of 148 administered cycles in 33 patients. Result(s): In 66% of patients PLD plus trabectedin was given as first-line treatment, in 19% and 14% as second and third-line treatment, respectively. After 6 months one patient (4.8%) achieved complete remission (CR), four others (19%) showed a partial remission (PR), resulting in an objective response rate (ORR) of 24%. Four patients (19%) showing stable disease (SD), resulting in a clinical benefit rate (= ORR + SD) of 43%; progression was recorded in 12 patients (57%). Median PFS was 6.0 months (SD: +/-21 months), while median overall survival was 26 months (SD: +/-32 months). A median of 4 (range: 1-11) cycles per patient were given. Regarding >= grade 3 toxicity, thrombocytopenia was recorded in 9%, anaemia in 12% and neutropenia in 36% of patients. Febrile neutropenia was present in 7 patients (21%). Haematologic toxicity was the most frequent reason for dose delays (25 events) and dose reductions in eight cases. Conclusion(s): Compared to conventional doxorubicin plus trabectedin, the herein investigated combination shows limited but similar anti-tumor efficacy in metastatic uterine sarcomas, but exhibits a more favourable toxicity profile. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Strojek, K., et al. (2023). "The Effects of Extracorporeal Magnetic Innervation in the Treatment of Women with Urinary Incontinence: A Systematic Review." Journal of Clinical Medicine 12(17): 5455.
	Purpose: The aim of this study is to identify and critically evaluate literature regarding the clinical efficacy of extracorporeal magnetic innervation (ExMI) in the treatment of female patients with urinary incontinence (UI). Method(s): An analysis was carried out using the following electronic databases: Medline, PubMed, ScienceDirect, and the Cochrane Library (data published between 2008 and 2023). Searches of the above databases were conducted in April 2023. Only randomized clinical studies (RCTs) in English studies were eligible for the study. Randomized controlled trials were included in the review and evaluated with the Downs and Black checklist. Result(s): Eleven studies met the inclusion criteria. Among these, two studies examined the use of ExMI and PMFT (pelvic floor muscle training) and three studies compared active ExMI versus sham ExMI. Four studies evaluated solely ExMI, and moreover, there was no control group in two of these studies. One study compared the effects of Kegel exercises with ExMI, while another study compared electrostimulation with ExMI. The reviewed studies exhibited significant differences in interventions, populations, and outcome measures. Conclusion(s): Extracorporeal magnetic stimulation has shown promise as an effective treatment for female urinary incontinence. Whether used alone or as a component of combination therapy, ExMI has the potential to enhance patients' quality of life (QoL) without significant safety concerns.Copyright © 2023 by the authors.

Strowitzki, T., et al. (2021). "Maternal and neonatal outcome and children's development after medically assisted reproduction with in-vitro matured oocytes-a systematic review and meta-analysis." Human Reproduction Update 27(3): 460-473.
	Background: IVM was implemented in medically assisted reproduction 25 years ago. IVM does not involve controlled ovarian stimulation (COS) and is mainly indicated in patients with a high risk of ovarian hyperstimulation syndrome, in particular in patients with polycystic ovary syndrome (PCOS); it is also an acknowledged option in fertility protection. However, the in-vitro culture of immature oocytes raises concerns over their developmental potential and the putative impact on children's health. Although an increasing number of studies on obstetric and neonatal outcomes of IVM children and their development have been published in recent years, study designs are difficult to compare, since IVM is used in women with various indications and IVM protocols do not follow the same standards.; Objective and Rationale: The aim of this systematic review was to evaluate the current evidence from IVM children of an impact of in-vitro culture of immature oocytes. Primary outcome parameters were birthweight and children's development up to the age of 2 years. We also compared pregnancy pathologies and the outcome of IVM children and COS children in relation to maternal indications, in particular PCOS, and to the type of IVM protocols with or without ovulation trigger as the secondary outcome parameters. IVM is an accepted clinical option for many centres; however, a comprehensive analysis of the available data is needed to establish whether the use of human oocytes that are fully matured in vitro is safe for both children and their mothers.; Search Methods: Google Scholar and PubMed were used for identifying peer-reviewed original articles and reviews through January 2020. A total of 191 studies were screened and 16 studies were included in the qualitative synthesis. Studies were stratified according to indications, the use of an ovulation trigger and multiplicity.; Outcomes: Birthweights of IVM singletons and multiples were comparable to their respective COS controls: birthweights were also similar if the analysis was restricted to mothers with PCOS. IVM children had a comparable birthweight to COS children, irrespective of whether an ovulation trigger was used in IVM cycles or not. The frequency of gestational diabetes (GD) in singleton pregnancies was comparable between IVM and COS, regardless of infertility background. There was also no difference in GD frequency between IVM and COS, if an hCG ovulation trigger in IVM cycles was used or not. Hypertensive disorders in singleton pregnancies of women with PCOS were significantly more frequent after IVM compared to COS, in particular if IVM cycles were performed only with in-vitro matured oocytes. There was no difference in the preterm birth rate of singleton pregnancies between IVM and COS. Preterm birth rates were still similar if only women diagnosed with PCOS were compared and whether an ovulation trigger in IVM was used or not. The malformation rate in IVM children did not differ in COS children versus children after natural conception. At the age of 2 years, IVM singletons showed similar anthropometric and mental development compared to COS children or children from natural conception.; Wider Implications: The higher incidence of hypertensive disorders in IVM pregnancies needs monitoring during pregnancy. Current data on the development of IVM children are encouraging, although the quality of many studies is limited and long-term data beyond 2 years are scarce. Further studies should be based on generally accepted IVM protocols. Studies on long-term outcomes beyond 2 years are needed to search for potential long-time sequelae of IVM. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Studniarek, A., et al. (2022). "TENSION-FREE VENTRAL RECTOPEXY- SHORT-TERM RESULTS." Diseases of the Colon and Rectum 65(5): 171-172.
	Purpose/Background: Two theories exist explaining the pathophysiology of rectal prolapse. First postulates that rectal prolapse is a sliding hernia through a defect in a pelvic fascia. Second suggests it is an internal intussusception of the rectum. There is no evidence to suggest which rectal fixation is superior. Aim(s): The primary aim was to evaluate the recurrence rate of tensionfree ventral rectopexy. The secondary aim was to assess post-op-erative morbidity, primarily new onset obstructed defecation symptoms. Method(s): Retrospective analysis of patients who underwent robotic tension free ventral rectopexy with or without sacrocolpopexy between November 2017 and July 2021 was performed. Robotic tension free rectopexy is a combination of ventral mesh rectopexy with additional mid rectal sutures and a right sided unilateral suture rectopexy. Patients were operated at a tertiary care center by a single colorectal surgeon. Recurrence was defined as a presence of full-thickness rectal prolapse at 1 month and 6-month after surgery. Results/Outcome(s): A total of 29 patients were included. Twentyone patients (72%) underwent robotic tension-free rectopexy and 8 patients (28%) underwent robotic tension free rectopexy and sacrocolpopexy. The median age was 63 years (range 20-93). There were 26 women (89.7%) and 3 mens (10.3%). All 29 patients had fullthickness rectal prolapse (Table 1). The average length of hospital stay was one day (range 1-20]) Two patients (6.8%) were readmitted; one had postoperative ileus, and one had unrelated anal pain. The median time to initial postoperative visit was 11 days (range 4-104). All 29 patients (100%) were seen during the initial postoperative visit, 26 (89.6%) were seen at 1 month visit, and twenty-two (75.8%) were seen at 6-month visit. None of the patients (0%) had early rectal prolapse recurrences at any of the post-operative visits. Twenty-six patients (89.6%) reported improved obstructed defecation symptoms, two patients (6.2%) had no changes in their bowel habits and one (3.4%) reported worsened symptoms. Limitation(s): The limitations include a small cohort of patients, retrospective analysis, and lack of power to compare to the existing rectopexy techniques. Conclusions/Discussion: Tension free ventral rectopexy is a surgical technique addressing the two existing theories behind pathophysiology of rectal prolapse and the limitations of ventral mesh rectopexy alone. This technique is a safe and a successful approach for the treatment of full thickness rectal prolapse with low recurrence rate and low morbidity, especially for patients with obstructed defecation. Tension free ventral rectopexy results in improved obstructed defecation symptoms; however, further long-term follow up and prospective trials are warranted to evaluate the long-term outcomes. (Table Presented).

Studnicki, J., et al. (2023). "A Cohort Study of Mental Health Services Utilization Following a First Pregnancy Abortion or Birth." International Journal of Women's Health 15: 955-963.
	Objective: To determine whether exposure to a first pregnancy outcome of induced abortion, compared to a live birth, is associated with an increased risk and likelihood of mental health morbidity. Material(s) and Method(s): Participants were continuously eligible Medicaid beneficiaries age 16 in 1999, and assigned to either of two cohorts based upon the first pregnancy outcome, abortion (n = 1331) or birth (n = 3517), and followed through to 2015. Outcomes were mental health outpatient visits, inpatient hospital admissions, and hospital days of stay. Exposure periods before and after the first pregnancy outcome, a total of 17 years, were determined for each cohort. Finding(s): Women with first pregnancy abortions, compared to women with births, had higher risk and likelihood of experiencing all three mental health outcome events in the transition from pre-to post-pregnancy outcome periods: outpatient visits (RR 2.10, CL 2.08- 2.12 and OR 3.36, CL 3.29-3.42); hospital inpatient admissions (RR 2.75, CL 2.38-3.18 and OR 5.67, CL 4.39-7.32); hospital inpatient days of stay (RR 7.38, CL 6.83-7.97 and OR 19.64, CL 17.70-21.78). On average, abortion cohort women experienced shorter exposure time before (6.43 versus 7.80 years), and longer exposure time after (10.57 versus 9.20 years) the first pregnancy outcome than birth cohort women. Utilization rates before the first pregnancy outcome, for all three utilization events, were higher for the birth cohort than for the abortion cohort. Conclusion(s): A first pregnancy abortion, compared to a birth, is associated with significantly higher subsequent mental health services utilization following the first pregnancy outcome. The risk attributable to abortion is notably higher for inpatient than outpatient mental health services. Higher mental health utilization before the first pregnancy outcome for birth cohort women challenges the explanation that pre-existing mental health history explains mental health problems following abortion, rather than the abortion itself.Copyright © 2023, Dove Medical Press Ltd. All rights reserved.

Stumbar Sarah, E. and S. Minor (2023). "Postpartum Care Up to One Year After Pregnancy: A Systematic Review and Meta-Analysis." American family physician 108(5): 506-508.
	
Stuopelytė, R., et al. (2023). "Quality of Life in Cervical Cancer Survivors Treated with Concurrent Chemoradiotherapy." Medicina (Kaunas, Lithuania) 59(4).
	Background and Objectives : Cervical cancer is the fourth most common cancer in women globally. As survival rates gradually increase, it becomes necessary to assess the quality of life (QoL) after treatment. It is known that different treatment modalities have different effects on QoL. Therefore, we aimed to evaluate the QoL of cervical cancer survivors (CCSs) treated with concurrent chemoradiotherapy (CCRT). Materials and Methods : A cross-sectional monocentric study, conducted in Vilnius university hospital Santaros klinikos between November 2018 and November 2022, included 20 women, who were interviewed once using the European Organization for Research and Treatment of Cancer (EORTC)-designed Quality-of-Life questionnaire cervical cancer module (QLQ-CX24). The sociodemographic and clinical data as well as the results of the questionnaire are presented in mean, standard deviation and percentages. The QoL scores were compared between different age and stage groups using the Mann-Whitney U test. Results : Twenty participants, aged from 27 to 55 years, with a mean age of 44 years (SD = 7.6) participated in the study. All the participants were CCSs with an International Federation of Gynecology and Obstetrics (FIGO) stage from IB to IIIB and all of them were treated with CCRT. The symptom experience was relatively low and revealed a good result (21.8, SD = 10.2). Mean scores on body image, sexual/vaginal functioning, menopausal symptoms and sexual worry scales indicated moderate functioning and a moderate level of some of the cervical cancer specific symptoms after CCRT. Sexual activity and sexual enjoyment of the CCSs were low (11.7 (SD = 16.3), 14.3 (SD = 17.8), respectively). Conclusions : Cervical cancer survivors report a relatively good quality of life regarding symptom experience; however, women following concurrent chemoradiotherapy tend not to be sexually active and rarely feel sexual enjoyment. In addition, this treatment modality negatively affects a woman's body image and self-perception as a woman.

Stute, P., et al. (2024). "Progestogens for endometrial protection in combined menopausal hormone therapy: A systematic review." Best Practice and Research: Clinical Endocrinology and Metabolism 38(1): 101815.
	Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen.Copyright © 2023 The Authors

Stuursma, A., et al. (2022). "Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning; A Systematic Literature Review." The Journal of Sexual Medicine 19(12): 1778-1789.
	Background: Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual symptoms.; Aims: To systematically review and meta-analyze the effect of systemic hormone replacement therapy (sHRT) on psychological well-being and sexual functioning in women after surgical menopause and BSO.; Methods: Medline/Pubmed, EMBASE and PsychInfo were systematically searched until November 2021. Randomized controlled trials investigating the effect of sHRT on psychological well-being and/or sexual functioning in surgically menopausal women and women after BSO were eligible for inclusion. Two independent authors performed study selection, risk of bias assessment and data extraction. Standardized mean differences (SMDs) were calculated.; Outcomes: Primary outcomes for psychological well-being were defined as overall psychological well-being, depression, and anxiety. Primary outcomes for sexual functioning were defined as overall sexual functioning, sexual desire, and sexual satisfaction. All outcomes were assessed on short (≤12 weeks) or medium term (13-26 weeks).; Results: Twelve studies were included. Estradiol had a beneficial effect on depressed mood on short term 3-6 years after surgery or 2 years (median) after surgery with high heterogeneity (SMD: -1.37, 95%CI: -2.38 to -0.37, P = .007, I 2 79%). Testosterone had a beneficial effect on overall sexual functioning on short to medium term 4.6 years (mean) after surgery (SMD 0.38, 95%CI 0.11-0.65, I 2 0%) and on sexual desire on medium term at least 3-12 months after surgery (SMD 0.38, 95%CI 0.19-0.56, I 2 54%). For most studies, risk of bias was uncertain.; Clinical Implications: Estradiol may beneficially affect psychological symptoms after surgical menopause or BSO and testosterone might improve sexual desire and overall sexual functioning.; Strengths and Limitations: This review only included patient-reported outcomes, thereby reflected perceived and not simply objective symptoms in surgically menopausal women and women after BSO. The small number of studies highly varied in nature and bias could not be excluded, therefore our results should be interpreted with great caution.; Conclusion: Independent randomized controlled clinical trials investigating the effects of estrogen-progesterone and testosterone on psychological and sexual symptoms after surgical menopause are needed.; Prospero Registration Number: CRD42019136698. Stuursma A, Lanjouw L, Idema DL, et al. Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning: A Systematic Literature Review. J Sex Med 2022;19:1778-1789. (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Su, G., et al. (2022). "Pantoprazole promotes the sensitivity of cervical cancer cells to cisplatin by inhibiting cisplatin-induced autophagy." Journal of cancer research and therapeutics 18(2): 362-369.
	Aim: This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin.; Methods: HeLa and CaSki cells were exposed to cisplatin and/or PPZ treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, flow cytometry, wound healing, and transwell assays were performed to detect cell viability, proliferation, apoptosis, migration, and invasion of CC cells, respectively. Then, expressions of Beclin-1, LC3, and p62 were measured by western blot. Rapamycin (Rapa), acting as an autophagy activator, was applied to confirm the effect of autophagy on the sensitivity of CC cells to cisplatin.; Results: Cisplatin treatment suppressed cell viability and proliferation and accelerated apoptosis of CC cells. Combination of cisplatin and PPZ or PPZ alone significantly inhibited cell viability, proliferation, migration, and invasion, and increased cell apoptosis of CC cells. Cisplatin enhanced expression levels of Beclin1 and LC3II/I, and reduced p62 expression. Combination of cisplatin and PPZ significantly decreased the expression levels of Beclin1 and LC3II/I, but increased p62 expression. The autophagy activator, Rapa, eliminated the inhibitory effects of the combination of cisplatin and PPZ on autophagy, and enhanced cell viability, but inhibited apoptosis of CC cells.; Conclusion: PPZ promotes the sensitivity of CC cells to cisplatin by inhibiting cisplatin-induced cell autophagy.; Competing Interests: None

Su, H., et al. (2023). "Menopausal symptoms and quality of life in female survivors treated with hematopoietic stem cell transplantation." Frontiers in Psychiatry 14: 1050959.
	Objectives: To assess the severity of menopausal symptoms and the correlation among different quality of life questionnaires and compare the quality of life of patients who underwent hematopoietic stem cell transplantation (HSCT) for hematological disorders with the norm group in order to facilitate personalized and directed therapeutic intervention for patients.; Methods: We recruited women who had premature ovarian failure (POF) after HSCT for hematologic diseases in the gynecological endocrinology outpatient clinic of Peking University People's Hospital. Women with HSCT were included in the study if they had 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels greater than 40 mIU/mL taken 4 weeks apart. The patients who had other causes of POF were excluded. During the survey, all women were required to fill out the questionnaires [Quality of Life Questionnaire (MENQOL), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and 36-item Short-Form (SF-36)] online. We analyzed the severity of menopausal symptoms, anxiety, and depression in Participants. In addition, differences on the SF-36 scale scores between the study group and norm groups were examined.; Results: In total, 227 (93.41%) patients completed the survey and were analyzed. The severity of all symptoms is "none and mild" in MRS, MENQOL, GAD-7, and PHQ-9. On the MRS, the most common symptoms were irritability, physical and mental exhaustion, and sleep problems. The severest symptoms were sexual problems (53, 73.82%), followed by sleep problems (44, 19.38%) and mental and physical exhaustion (39, 17.18%). In the MENQOL, the most common symptoms were psychosocial and physical symptoms. The severest symptoms were sexual symptoms (35, 48.75%) followed by psychosocial symptoms (23, 10.13%). Moderate-severe scores were shown in 11.89% (27) and 18.72% (42) cases in the GAD-7 and PHQ-9, respectively. Based on SF-36, in comparison with the norm group, the HSCT participants had higher vitality scores and lower role physical, physical functioning, and role emotional scores aged 18-45. In addition, the HSCT participants had lower mental health scores aged 18-25, and lower general health scores aged 25-45. No strong correlation was observed between questionnaires in our study.; Conclusion: Overall, menopausal symptoms are milder in female patients after HSCT. There is no single scale that comprehensively assesses the patient's quality of life after HSCT. We need to assess the severity of various symptoms in patients using different scales.; Competing Interests: The authors declare that this study received funding from Roche Diagnostics. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. (Copyright © 2023 Su, Li, Zhang, Yang and Wang.)

Su, M., et al. (2023). "2-Deoxy-D-glucose simultaneously targets glycolysis and Wnt/β-catenin signaling to inhibit cervical cancer progression." IUBMB life 75(7): 609-623.
	Cervical cancer is one of the most common female malignant tumors, with typical cancer metabolism characteristics of increased glycolysis flux and lactate accumulation. 2-Deoxy-D-glucose (2-DG) is a glycolysis inhibitor that acts on hexokinase, the first rate-limiting enzyme in the glycolysis pathway. In this research, we demonstrated that 2-DG effectively reduced glycolysis and impaired mitochondrial function in cervical cancer cell lines HeLa and SiHa. Cell function experiments revealed that 2-DG significantly inhibited cell growth, migration, and invasion, and induced G0/G1 phase arrest at non-cytotoxic concentrations. In addition, we found that 2-DG down-regulated Wingless-type (Wnt)/β-catenin signaling. Mechanistically, 2-DG accelerated the degradation of β-catenin protein, which resulted in the decrease of β-catenin expression in both nucleus and cytoplasm. The Wnt agonist lithium chloride and β-catenin overexpression vector could partially reverse the inhibition of malignant phenotype by 2-DG. These data suggested that 2-DG exerted its anti-cancer effects on cervical cancer by co-targeting glycolysis and Wnt/β-catenin signaling. As expected, the combination of 2-DG and Wnt inhibitor synergistically inhibited cell growth. It is noteworthy that, down-regulation of Wnt/β-catenin signaling also inhibited glycolysis, indicating a similar positive feedback regulation between glycolysis and Wnt/β-catenin signaling. In conclusion, we investigated the molecular mechanism by which 2-DG inhibits the progression of cervical cancer in vitro, elucidated the interregulation between glycolysis and Wnt/β-catenin signaling, and preliminarily explored the effect of combined targeting of glycolysis and Wnt/β-catenin signaling on cell proliferation, which provides more possibilities for the formulation of subsequent clinical treatment strategies. (© 2023 International Union of Biochemistry and Molecular Biology.)

Su, M.-H., et al. (2022). "Comparing paclitaxel-platinum with ifosfamide-platinum as the front-line chemotherapy for patients with advanced-stage uterine carcinosarcoma." Journal of the Chinese Medical Association : JCMA 85(2): 204-211.
	Background: Uterine carcinosarcoma (UCS) is a rare but highly lethal disease. Adjuvant chemotherapy is highly recommended for advanced UCS. To date, the standard chemotherapy regimen is still uncertain, although two regimens as paclitaxel-platinum (PP) and ifosfamide-platinum (IP) regimens are most commonly used. The aims of the current study attempt to compare both regimens in the management of advanced UCS patients.; Methods: We evaluated advanced UCS patients who were treated either with PP or with IP after primary cytoreductive surgery in single institute retrospectively. The clinical-pathological parameters, recurrence, and survival were recorded.; Results: A total of 16 patients were analyzed. Twelve patients received adjuvant PP therapy, and the remaining four patients received IP therapy. The median follow-up time was 28 months, ranging from 3.8 months to 121 months. Disease-related death occurred in 10 patients (62.5%). The median progression-free survival was 4.9 months, ranging from 3.8 months to 36.5 months in IP, and 23.1 months, ranging from 9.3 months to 121 months in PP, with statistically significant difference (p = 0.04). The median overall survival was 9.5 months (ranging from 3.8 months to 36.5 months) and 28.7 months (ranging from 10.3 months to 121 months) in IP and PP, respectively, without statistically significant difference (p = 0.06). Presence of pelvic and para-aortic lymphadenopathy and deep myometrial invasion (>1/2) were associated with worse prognosis by univariate analysis. No prognostic factor could be identified using multivariate analysis model.; Conclusion: In the current study, due to extremely little number of subjects enrolled, the advantage of using paclitaxel-platinum regimen in the management of advanced UCS was still unclear, although a certain trend of favoring was supposed. We are looking forward to seeing more studies to identify the approximate regimen in the management of this highly lethal disease.; Competing Interests: Conflicts of interest: Dr. Peng-Hui Wang, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. (Copyright © 2021, the Chinese Medical Association.)

Su, P., et al. (2023). "ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer." Journal of experimental & clinical cancer research : CR 42(1): 274.
	Background: Tumor cells can resist chemotherapy-induced pyroptosis through glycolytic reprogramming. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. Herein, we refine the oncogenic role of ERRα in the pyroptosis pathway and glycolytic metabolism.; Methods: The interaction between ERRα and HIF-1α was verified using co-immunoprecipitation. The transcriptional binding sites of ERRα and NLRP3 were confirmed using dual-luciferase reporter assay and cleavage under targets and tagmentation (CUT&Tag). Flow cytometry, transmission electron microscopy, scanning electron microscopy, cell mito stress test, and extracellular acidification rate analysis were performed to investigate the effects of ERRα on the pyroptosis pathway and glycolytic metabolism. The results of these experiments were further confirmed in endometrial cancer (EC)-derived organoids and nude mice. In addition, the expression of ERRα-related pyroptosis genes was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus database.; Results: Triggered by a hypoxic microenvironment, highly expressed ERRα could bind to the promoter of NLRP3 and inhibit caspase-1/GSDMD signaling, which reduced inflammasome activation and increased pyroptosis resistance, thereby resulting in the resistance of cancer cells to cisplatin. Moreover, ERRα activated glycolytic rate-limiting enzyme to bridge glycolytic metabolism and pyroptosis in EC. This phenomenon was further confirmed in EC-derived organoids and nude mice. CUT & Tag sequencing and The Cancer Genome Atlas database analysis showed that ERRα participated in glycolysis and programmed cell death, which resulted in EC progression.; Conclusions: ERRα inhibits pyroptosis in an NLRP3-dependent manner and induces glycolytic metabolism, resulting in cisplatin resistance in EC cells. (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Su, Q., et al. (2022). "The efficacy of mifepristone combined with methotrexate for the treatment of ectopic pregnancy: a systematic review and meta-analysis*." Annals of medicine 54(1): 3269-3285.
	Objective: Systematically evaluate the clinical efficacy of mifepristone combined with methotrexate therapy for ectopic pregnancy (EP), analyze the experimental designs, put forward improvement ideas. Method(s): RCTs of mifepristone combined with mifepristone for EP until January 2022 in six databases were searched. The primary outcome indicator was the cure rate. RevMan 5.4 was used to analyse and the online GRADEpro tool was used to assess the certainty of the evidence. Result(s): Twenty-five RCTs involved 2263 patients. The cure rate was higher in the investigational group (OR = 4.09, 95%CI: [3.20, 5.22]), time of vagina stopped bleeding (MD = -11.21, 95%CI: [-11.85, -10.57]) and time of abdominal pain disappeared (MD = -6.24, 95%CI: [-6.63, -5.86]) were shorter in the investigational group, beta-HCG level (MD = -585.32, 95%CI: [-609.62, -561.03]) was lower and diameter of the mass (MD = -1.23, 95%CI: [-1.40, -106]) was smaller in the investigational group. The certainty of the evidence for most outcomes was moderate or high, and only one was low. Conclusion(s): The combination of mifepristone and methotrexate can improve the efficacy of ectopic pregnancy without amplifying the toxic side effects. Larger scale and better design of the randomized controlled trials are needed.KEY MESSAGES In recent years, the increase in ectopic pregnancies and their impacts on female fertility makes physicians have to find an effective medical treatment as soon as possible that can avoid surgery. The mifepristone combined with methotrexate therapy for EP has better curative effects on improving the cure rate, lowering beta-HCG level, reducing the mass, and alleviating symptoms of abdominal pain and bleeding, without amplifying the toxic side effects. Literature with high quality is lacking, and well-designed, large-scale and high-quality multicenter randomized controlled trials are needed.Copyright © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Su, R., et al. (2021). "A systematic review of the effects of emotional support on postpartum depression in Asia."
	
Su, S., et al. (2022). "Luteal phase support for natural cycle frozen embryo transfer: a meta-analysis." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(2): 116-123.
	Purpose: We aimed to evaluate the effect of luteal phase support (LPS) on pregnancy outcome in natural cycle frozen embryo transfer (NC-FET).; Method: We searched PubMed, Cochrane Library, Embase for related literature from start to February 2020. Relative risk ratio (RR) and 95% confidence intervals (95% CI) in random-effects, fixed-effects models were calculated using Review Manager 5.3.; Results: Totally 9 studies were included in the meta-analysis. The results showed no significant difference could be found regarding chemical pregnancy rate (RR 1.07, 95% CI 0.93-1.22; I 2 = 54%) and miscarriage rate (RR 0.92, 95% CI 0.70-1.22; I 2 = 0%) between the LPS groups and no LPS groups in NC-FET. LPS groups has increased the rate of clinical pregnancy rate (RR 1.23, 95% CI 1.12-1.34; I 2 = 52%) compared with no LPS groups. Subgroup analysis according to trigger administration also showed a significant difference between the two groups.; Conclusion: LPS might improve the clinical pregnancy rate in NC-FET. HCG trigger for ovulating may result in luteal phase deficiency. LPS subsequently improved clinical pregnancy rate and chemical pregnancy rate for patients undergoing HCG trigger and NC-FET.; Retrospectively Registered: This meta-analysis was registered at PROSPERO, PROSPERO ID is CRD42020171758.

Su, V., et al. (2022). "Depression and anxiety in women 6 months after hypertensive pregnancy: A blood pressure postpartum (BP2) sub-study." Obstetric Medicine 15(1 Supplement): 17.
	Background/objectives: Hypertensive disorders of pregnancy (HDP) have been associated with postpartum mental health sequelae. However, limited evidence exists on how this risk may differ between subgroups. This sub-study aimed to compare mental health (depression and anxiety) between blood pressure postpartum (BP2) subgroups at baseline (6 months postpartum). Method(s): Sub-study of the in-progress BP2 study, a randomised controlled trial investigating lifestyle interventions after HDP. Data obtained approximately 6 months postpartum from BP2 pre-randomisation questionnaires, including the Edinburgh Postnatal Depression Scale (EPDS) and General Anxiety Disorder 7-item scale (GAD-7). Major subgroups compared included (a) Type of HDP (preeclampsia (PE), gestational hypertension (GH), chronic hypertension (CH)+/-superimposed PE + CH), (b) body mass index (BMI; <30, >=30), (c) primiparous versus multiparous and (d) preterm versus term birth. Result(s): A total of 212 women (29 CH, 57 GH, 113 PE and 14 PE +CH) randomised to August 2020. In the overall cohort, 2% had a non-zero answer to Q10 (suicidal ideation) on the EPDS, 10% scored above the EPDS cut-off (>12) and 5% scored above the GAD-7 cut-off (>10) at 6-months postpartum. In comparing HDP subtypes, 22% PE+CH scored above the GAD-7 cut-off compared to 7% CH, 5% GH and 3% PE (p= 0.023). A higher proportion of PE+CH (14%) expressed any suicidal ideation on the EPDS compared to 0% CH, 2% GH and 2% PE (p =0.023). Women with BMI >=30 (18%) scored above the EPDS cut-off compared to women with BMI <30 (7%, p=0.01). No significant differences were noted by parity or term versus preterm birth. Conclusion(s): Women with previous PE+CH and/or BMI >=30 appear more at risk of depression and anxiety than other women post-HDP. This has implications for guiding postpartum management, including increased screening and additional psychological follow-up. Further research, including an examination of confounders, is needed to strengthen these conclusions.

Su, V., et al. (2021). "Depression and anxiety in women 6 months after hypertensive pregnancy: a Blood Pressure Postpartum (BP2) sub-study." Pregnancy hypertension 25: e60.
	Background/Objectives: Hypertensive disorders of pregnancy (HDP) have been associated with postpartum mental health sequelae. This study aimed to compare mental health (depression and anxiety) between Blood Pressure Postpartum (BP2) subgroups at baseline (6‐months postpartum). Methods: Sub‐study of the in‐progress BP2 study, a randomised controlled trial investigating lifestyle interventions after HDP. Data obtained approximately 6‐months postpartum from BP2 pre‐randomisation questionnaires, including the Edinburgh Postnatal Depression Scale (EPDS) and General Anxiety Disorder 7‐item scale (GAD‐7). Major subgroups compared included (a) HDP subtype (preeclampsia PE, gestational hypertension GH, chronic hypertension CH ± superimposed preeclampsia PE+CH) and (b) BMI (<30, ≥30). Results: 212 women (29 CH, 57 GH, 113 PE and 14 PE+CH) randomised to August 2020. In the overall cohort, 2% had a non‐zero answer to Q10 (suicidal ideation) on the EPDS, 10% scored above the EPDS cut‐off (>12) and 5% scored above the GAD‐7 cut‐off (>10) at 6‐months postpartum. In comparing HDP subtypes, 22% PE+CH scored above the GAD‐7 cut‐off compared to 7% CH, 5% GH and 3% PE (p=0.023). More PE+CH also demonstrated some suicidal ideation on EPDS (14%) versus 0% CH, 2% GH and 2% PE (p=0.023). Women with BMI ≥30 (18%) scored above the EPDS cut‐off versus women with BMI <30 (7%, p=0.01). Conclusions: Women with previous PE+CH and/or BMI ≥30 appear more at risk of depression and anxiety than other women post‐HDP. This has implications in guiding postpartum management, including increased screening and additional psychological follow‐up. Further research, including examination of confounders, is needed to strengthen these conclusions.

Su, Y., et al. (2022). "Effect and rational application of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia." Photodiagnosis and photodynamic therapy 37: 102634.
	Background: Lesions in both the cervix and vagina require an efficacious non-invasive treatment therapy such as 5-Aminolevulinic acid photodynamic therapy(5-ALA-PDT). In this study, we evaluate clinical efficacy and safety of 5-ALA PDT for cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia (CIN & VAIN).; Methods: A retrospective analysis was performed on 48 patients diagnosed with CIN & VAIN and receiving 5-ALA PDT. All patients were first followed up at 3, 6 and 12 months after treatment, then every 6 months thereafter.; Results: Out of 1051 patients referred for CIN (4.56%), 48 were diagnosed with CIN&VAIIN. The patients had statistically significant average vaginal and cervical lesion areas of 1.22 and 0.41 cm 2 respectively. 4 patients were lost during follow-up. The patients' complete remission (CR) rate was 88.64% (39/44) at 3-6 months after treatment, while the total HPV clearance rate was 46.34 and 60.98% at 3- and 12-months follow-up,respectively. HPV16/18 combined with other high-risk human papillomaviruses (hrHPV) (HPV16/18 and other hrHPV) infection exhibited a lower HPV clearance rate (P = 0.006). The treatment time in high-grade intraepithelial neoplasia (HSIL) was higher than that of low-grade intraepithelial neoplasia (LSIL). Notably, atypical vessels and endocervical canal lesions involvement significantly affected 5-ALA PDT. Moreover, 5 patients had residual lesions (11.36%) during follow-up, one patient presented recurrence (2.56%), while 4 had successful pregnancy.; Conclusions: 5-ALA-PDT is a non-invasive, effective, and safe therapy for treating CIN & VAIN and can maintain the structural and functional integrity of target organs. However, its efficacy is relatively poor in patients with endocervical canal lesions involvement, atypical vessels, and HPV16/18 and other hrHPV infection. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Subbiah, V., et al. (2024). "Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies." Cancer research communications 4(2): 378-387.
	Background: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5'-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors.; Methods: Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500-1,500 mg). All patients underwent 14-day titration period for metformin in cycle 1. Tumor measurements were performed following cycle 2 and subsequently every 8 weeks.; Results: A total of 30 patients were enrolled across four cohorts (3 mg/500 mg; 3 mg/1,000 mg, 4 mg/1,000 mg; 4 mg/1,500 mg). 19 were female (63%), median age was 57 (range: 30-77), all were Eastern Cooperative Oncology Group performance status 1. Tumor types included sarcoma (6), breast (4), ovarian (4), head and neck (3), colorectal (2), lung (2), renal cell (2), endometrial (2), gastroesophageal junction (1), prostate (1), stomach (1), urachus (1), and cervical cancer (1). Median number of prior lines of therapy was 4. Most common genomic alterations included PIK3CA (27%), PTEN (17%), AKT1/2 (10%), mTOR (10%). Of 30 patients evaluable for response, 4 patients achieved partial response (PR); 15 patients achieved stable disease (SD) as best response. Disease control rate (PR+SD) was 63%. Of the responders in PR, 3 of 4 patients had documented PTEN mutations (3/5 patients enrolled with PTEN mutations had PR); 2 of 4 of patients in PR had comutations (patient with leiomyosarcoma had both PTEN and TSC; patient with breast cancer had both PTEN and STK11); 1 of 4 patients in PR had AKT and mTOR mutation; tumor types included leiomyosarcoma (n = 2), breast (n = 1), and endometrial cancer (n = 1). Most common treatment-emergent adverse events included nausea, anorexia, diarrhea, and rash. Grade (G) 3-5 treatment-related adverse events included hyperglycemia (4/30; 13%), fatigue (2/30; 7%), hypertriglyceridemia (1/30; 3%), rash (2/20; 7%), diarrhea (2/30; 7%), creatinine increase (1/30; 3%), acidosis (1/30; 3%). No dose-limiting toxicities (DLT) were reported in the 3 mg/500 mg cohort. One of 6 patient had DLT in the 3 mg/1,000 mg cohort (G3 diarrhea) and 2 of 11 patients had DLTs in the 4 mg/1,500 mg cohort (G3 fatigue, G3 rash). 4 mg/1,000 mg was defined as the MTD.; Conclusions: The safety profile of mTORC1/2 inhibitor sapanisertib in combination with metformin was generally tolerable, with antitumor activity observed in patients with advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations.; Significance: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, next-generation dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of AMPK suggesting combination therapy may enhance antitumor activity of sapanisertib. This dose-escalation study of sapanisertib and metformin in advanced solid tumors and mTOR/AKT/PI3K pathway alterations, demonstrates safety, tolerability, and early clinical activity in advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations.Clinical trial information: NCT03017833. (© 2024 The Authors; Published by the American Association for Cancer Research.)

Subbiah, V., et al. (2022). "FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies." Annals of oncology : official journal of the European Society for Medical Oncology 33(5): 522-533.
	Background: The phase I/II FIGHT-101 study (NCT02393248) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of pemigatinib, a potent and selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor, as monotherapy or in combination therapy, for refractory advanced malignancies, with and without fibroblast growth factor (FGF) and receptor (FGFR) gene alterations.; Patients and Methods: Eligible, molecularly unselected patients with advanced malignancies were included in part 1 (dose escalation; 3 + 3 design) to determine the maximum tolerated dose. Part 2 (dose expansion) evaluated the recommended phase II dose in tumors with or where FGF/FGFR activity is relevant.; Results: Patients (N = 128) received pemigatinib 1-20 mg once daily intermittently (2 weeks on/1 week off; n = 70) or continuously (n = 58). No dose-limiting toxicities were reported. Doses ≥4 mg were pharmacologically active (maximum tolerated dose not reached; recommended phase II dose 13.5 mg once daily). The most common treatment-emergent adverse event (TEAE) was hyperphosphatemia (75.0%; grade ≥3, 2.3%); the most common grade ≥3 TEAE was fatigue (10.2%). Dose interruption, dose reduction, and TEAE-related treatment discontinuation occurred in 66 (51.6%), 14 (10.9%), and 13 (10.2%) patients, respectively. Overall, 12 partial responses were achieved, most commonly in cholangiocarcinoma (n = 5) as well as in a broad spectrum of tumors including head and neck, pancreatic, gallbladder, uterine, urothelial carcinoma, recurrent pilocytic astrocytoma, and non-small-cell lung cancer (each n = 1); median duration of response was 7.3 months [95% confidence interval (CI) 3.3-14.5 months]. Overall response rate was highest for patients with FGFR fusions/rearrangements [n = 5; 25.0% (95% CI 8.7% to 49.1%)], followed by those with FGFR mutations [n = 3; 23.1% (95% CI 5.0% to 53.8%)].; Conclusions: Pemigatinib was associated with a manageable safety profile and pharmacodynamic and clinical activity, with responses seen across tumors and driven by FGFR fusions/rearrangements and mutations. These results prompted a registrational study in cholangiocarcinoma and phase II/III trials in multiple tumor types demonstrating the benefit of precision therapy, even in early phase trials.; Competing Interests: Disclosure VS reports a consulting or advisory role with Incyte Corporation; grants from Eli Lilly/Loxo Oncology, Blueprint Medicines Corporation, Turning Point Therapeutics, Boston Pharmaceuticals; research funding from Helsinn Pharmaceuticals, during the conduct of the study; research funding and consulting or advisory role with Eli Lilly/Loxo Oncology, during the conduct of the study; research funding from Roche/Genentech, Bayer, GlaxoSmithKline, NanoCarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berg Health, Incyte Corporation, Fujifilm, D3, Pfizer, MultiVir, Amgen, AbbVie, Alfasigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Altum Pharmaceuticals, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, NCI-CTEP, University of Texas MD Anderson Cancer Center, Turning Point Therapeutics, Boston Pharmaceuticals, Novartis, Pharmamar, MedImmune; an advisory board/consultant position with Helsinn, Incyte Corporation, QED Pharma, Daiichi-Sankyo, Signant Health, Novartis, Janssen, Relay Therapeutics, Roche, MedImmune; travel funds from Pharmamar, Incyte Corporation, ASCO, ESMO; other support from Medscape. MG reports stock in and has other ownership of COTA; has a consulting or advisory role with Bayer, Eli Lilly & Company, and Karyopharm Therapeutics; participates in the speakers’ bureau for Bristol Myers Squibb, Eli Lilly & Company, FoundationOne Inc., and Merck; received research funding (institutional) from AbbVie, Acceleron Pharma, Bayer, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Eli Lilly & Company, EMD Serono, Esanex, Genentech/Roche, Gilead Sciences, Incyte Corporation, Karyopharm Therapeutics, Loxo Oncology, MedImmune, Merck, Mirati Therapeutic , Moderna Therapeutics, Novartis, Regeneron, Rexahn Pharmaceuticals, Sanofi, Seattle Genetics, Tesaro, and TG Therapeutics. DCS reports research funding (institutional) from Agensys, Astellas Pharma, Bayer, Bristol Myers Squibb/Medarex, Eli Lilly & Company, ESSA, Exelixis, Genentech, Incyte Corporation, MedImmune, Medivation/Astellas, Merck, Millendo, Novartis, OncoMed, and Seattle Genetics. IMS reports employment and stock ownership with Repare Therapeutics. LF, CFL, CT, and TJ report employment and stock ownership with Incyte Corporation. MS reports participating in the speakers’ bureau for Novartis. NOI has declared no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Subhadra, E., et al. (2022). "Systematic review and meta-analysis of hypnotherapy for chronic pelvic pain."
	
Subhan, A., et al. (2022). "Targeted siRNA nanotherapeutics against breast and ovarian metastatic cancer: a comprehensive review of the literature." Nanomedicine (London, England) 17(1): 41-64.
	Metastasis is considered the major cause of unsuccessful cancer therapy. The metastatic development requires tumor cells to leave their initial site, circulate in the blood stream, acclimate to new cellular environments at a remote secondary site and endure there. There are several steps in metastasis, including invasion, intravasation, circulation, extravasation, premetastatic niche formation, micrometastasis and metastatic colonization. siRNA therapeutics are appreciated for their usefulness in treatment of cancer metastasis. However, siRNA therapy as a single therapy may not be a sufficient option for control of metastasis. By combining siRNA with targeting, functional agents or small-molecule drugs have shown potential effects that enhance therapeutic effectiveness. This review addresses multidrug resistance and metastasis in breast and ovarian cancers and highlights drug-delivery strategies using siRNA therapeutics.

Suchan Victoria Ayla, M. (2022). "Examining the acceptability and effectiveness of transdiagnostic, internet-delivered cognitive behaviour therapy for symptoms of postpartum anxiety and depression: A randomized controlled trial." Dissertation Abstracts International: Section B: The Sciences and Engineering 83(10-B): No-Specified.
	Following childbirth, women experience significant biological, physical, social, andemotional changes, wherein 20% of new mothers experience clinically impairingsymptoms of anxiety and/or depression. These conditions are associated with negativeeffects on both mother and child, underscoring the importance of ensuring treatmentoptions are widely available. While efficacious treatments like cognitive behaviourtherapy (CBT) exist, new mothers often report barriers to accessing in-person servicesincluding time concerns, stigma, and childcare difficulties. Importantly, many of thesebarriers can be mitigated using Internet-delivered CBT (ICBT), which has been found tobe effective in the treatment of various mental health concerns, including depression andanxiety. As postpartum anxiety and depression are often comorbid, transdiagnostic ICBTis a particularly promising treatment approach to investigate. The current study exploredthe feasibility, acceptability, and effectiveness of a transdiagnostic ICBT program, the Wellbeing Course for New Moms, with a sample of Saskatchewan women who had aninfant less than one year of age. Participants (N = 60) endorsing symptoms of depressionor anxiety were randomly assigned to the Wellbeing Course for New Moms or a waitlistcontrol (WLC) group. Participants completed measures pre-treatment, post-treatment,and 1-month follow up. Treatment satisfaction, therapeutic alliance, and open-endedquestions assessing participant experiences with treatment were also explored. Thetreatment group exhibited large within-group effect sizes on all primary measures ofanxiety and depression (Hedge's g: 0.89-1.24) and symptom improvement wasmaintained at follow-up. Medium to large between-group effect sizes were noted on allsymptom measures favouring the treatment group at post-questionnaires (Hedge's g:0.51-0.80) and follow-up (Hedge's g: 0.51-0.87); significantly more participants in thetreatment group were found to have reliably recovered in terms of depression and anxietyas compared to the WLC. Participants were satisfied with this treatment modality andwere able to establish a strong working alliance with their online therapist. The analysesrevealed that both treatment and WLC participants experienced statistically significantreductions in anxiety, depression, and distress over time, as well as improvements inmother-infant bonding (all ps < 0.05). The treatment group reported significantly superiorproportionate reductions in symptoms of anxiety and distress as compared to the WLC.;however, there were no statistically significant differences observed between the twogroups on depression measures. Of note, the current study was not reliably powered todetect medium or small differences due to the sample size. Results from the current studyprovide emerging evidence for transdiagnostic ICBT in the treatment of postpartumanxiety and depression. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Suchona, R., et al. (2023). "The effect of Eye Movement Desensitisation and Reprocessing (EMDR) Therapy for patients with chronic and acute pain: A systematic review."
	
Sudhakar, P., et al. (2024). "Surgical Treatment for Polycystic Ovary Syndrome and Reproductive Outcomes: A Retrospective Study." Journal of South Asian Federation of Obstetrics and Gynaecology 16(2): 107-110.
	Aim: To assess the reproductive outcome after ovarian drilling by laparoscopic technique, and also to analyze a number of penetrations per ovary to improve the ART outcome. Material(s) and Method(s): A retrospective study was performed at Sudha Hospital and Research Institute, Erode, Tamil Nadu over a period from January 2018 to December 2020. This study includes 254 infertile women with polycystic ovary syndrome (PCOS) and clomiphene-citrate resistance, who were subjected to ovarian drilling by laparoscopy using a drilling needle. Patients are divided into 2 groups, 1st group had less than 4 penetrations per ovary and 2nd group had above 4 penetrations per ovary. The results elicited from both the groups were compared. Result(s): The 2 groups did not show any significant difference about body mass index (BMI), insulin, and glucose levels before and after the procedure. The confirmed pregnancy was 79.2% in the group with 4 punctures and it was 74.6% in the group with more than 4 punctures. The miscarriage rate was 8.1% and 13.9% in the group with punctures less than 4 and more than 4 respectively. Significant improvement (p-value = 0.029) in live birth rate (70.3%) was observed in the group with less than 4 punctures. Conclusion(s): Ovarian drilling is a successful treatment in patients with clomiphene citrate-resistant PCOS. A remarkable improvement was observed in the confirmed pregnancy rate in patients who were subjected to ovarian drilling. It was observed that 4 penetrations per ovary were adequate to increase the outcome in comparison to more than 4 punctures per ovary.Copyright © The Author(s). 2024 Open Access.

Sudhakar, P., et al. (2022). "Does Adenomyosis Influence ICSI Clinical Outcome? A Systematic Analysis and Impact of GnRH Agonist Pretreatment for Women with Adenomyosis in ICSI-FET Cycle: A Retrospective Cohort Study." Journal of obstetrics and gynaecology of India 72(3): 236-242.
	OBJECTIVE: To evaluate the impact of adenomyosis on pregnancy outcome in ICSI/FET cycles and the beneficial effect of GnRH agonist pretreatment, conservative surgery or combination therapy on pregnancy outcome. MATERIALS AND METHODS: This is a retrospective cohort study where 613 ICSI cycles done in the period from Jan 2018 to Dec 2020 in Sudha infertility centre, Erode were analyzed. Study populations include 235 women with adenomyosis undergoing ICSI/FET cycle. RESULT: Overall, the outcome in terms of clinical pregnancy rate, miscarriage rate, live birth date and ongoing pregnancy rate was lower in women with adenomyosis following ICSI/FET cycles. We found significant improvement in clinical pregnancy rate who had pretreatment with GnRH agonist, conservative surgery or combination therapy. CONCLUSION: Adenomyosis as such has detrimental effect on ICSI clinical outcome. Pretreatment with GnRH agonist and conservative surgery and GnRH agonist long protocol could be beneficial. Further large scale prospective comparative studies are needed to confirm this result.

Sue, B., et al. (2021). "Effectiveness of aromatherapy for prevention or treatment of disease, medical or preclinical conditions, and injury: a systematic review."
	
Suff, N., et al. (2021). "Optimal timing of cervical cerclage removal following preterm premature rupture of membranes; a retrospective analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 259: 75‐80.
	OBJECTIVE: Preterm prelabour rupture of membranes occurs in over one third of pregnant women with a cervical cerclage in situ. In the setting of preterm prelabour rupture of membranes, clinicians are faced with the difficult decision of the optimal timing for removing the cerclage. We compared the maternal and neonatal outcomes following immediate removal or retention of the cervical cerclage. STUDY DESIGN: Women were retrospectively identified from St Thomas's Hospital Preterm Surveillance clinic database. Asymptomatic women with preterm prelabour rupture of membranes were identified and separated into those that had the cerclage removed and those that had the cerclage retained within 24 h of presentation. Women who were symptomatic at presentation and who delivered within 24 h of presentation were excluded from the analysis. Maternal outcomes measured were latency between preterm prelabour rupture of membranes and delivery, gestation at delivery and maternal chorioamnionitis and infection markers. Neonatal outcomes including birthweight and Apgar scores were also measured. RESULTS: 43 women with cerclage retained for over 24 h following preterm prelabour rupture of membranes were compared to 25 women in whom the cerclage was removed. The latency between preterm prelabour rupture of membranes and delivery was on average 70.4 h longer in women who had their cerclage retained compared to the removed group (p = 0.009). Rates of chorioamnionitis, maternal blood results, neonatal birthweight and Apgar scores did not differ significantly between the two groups, however a trend towards higher rates of chorioamnionitis (60 % vs 45 %) were seen in the retained group. CONCLUSION: Cervical cerclage retention in women following preterm prelabour rupture of membranes was associated with a longer latency period to delivery and was not significantly associated with any adverse obstetric, maternal or neonatal outcomes. Therefore, in women at risk of spontaneous preterm birth, cerclage retention may be beneficial, however these women and their babies should be monitored closely for any signs of infection. Further prospective randomised controlled studies assessing these outcomes as well as longer‐term outcomes in these women and their children are needed.

Sugarbaker Paul, H. (2022). "Optimizing regional chemotherapy for epithelial ovarian cancer." The Journal of Obstetrics and Gynaecology Research 48(6): 1306-1317.
	Aim: The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience.; Methods: Regional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long-term.; Results: An important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials.; Conclusions: Innovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions. (© 2022 Japan Society of Obstetrics and Gynecology.)

Sugaya, K., et al. (2021). "Dietary glycine improves urine storage symptoms in urology outpatients." Journal of complementary & integrative medicine 18(3): 617‐620.
	OBJECTIVES: Spinal glycinergic mechanisms inhibit the micturition reflex, and administration of glycine inhibits bladder activity in rats. Therefore, we examined whether dietary glycine would improve storage symptoms in urological outpatients. METHODS: We enrolled 20 participants (16 men and four women) with an overactive bladder symptom score (OABSS) ≥ 3. All participants took 3 g of glucose (placebo) twice a day for the first four weeks, then 3 g of glycine twice a day for the next four weeks. We evaluated blood pressure, international prostate symptom score (IPSS), nocturia quality of life (N‐QOL) score, OABSS, frequency of urination, sleep latency, time to first nighttime void, bladder pain, global self‐assessment (GSA) evaluated urinary symptom improvement, and adverse events. RESULTS: Glucose administered as a placebo improved urinary frequency, urine force on the IPSS, and five of the 13 items on the N‐QOL. However, compared to the results before and after glucose administration, glycine treatment decreased the number of nocturnal voids, urgency, and total score for urine storage items on the IPSS. It also reduced blood pressure and improved IPSS‐QOL. For the OABSS, improvements with glycine were noted in the number of nocturnal urinations, urinary urgency, urge incontinence, and total score. For the N‐QOL, eight of 13 items, and the total score, improved. The actual number of nighttime urinations, sleep latency, latency to first nighttime urination, bladder pain, and GSA also improved. There were no adverse events. CONCLUSIONS: Glycine might improve urine storage symptoms, cardiovascular function, pain, and sleep.

Suh Young, J., et al. (2022). "Bevacizumab versus PARP-inhibitors in women with newly diagnosed ovarian cancer: a network meta-analysis." BMC Cancer 22(1): 346.
	Background: In women with newly diagnosed ovarian cancer, bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) exhibit improved progression-free survival (PFS) when administered concurrent with chemotherapy and/or maintenance therapy, but no study has directly compared their effects. Therefore, this study aimed to compare the efficacy and safety of bevacizumab and PARPi in women with newly diagnosed ovarian cancer using a network meta-analysis.; Methods: PubMed, Medline, and Embase databases were searched, and five randomized trials assessing PFS in women with newly diagnosed ovarian cancer treated with either bevacizumab, PARPi, or placebo or no additional agent (controls) were identified. PFS was compared in the overall population with ovarian cancer, women with a BRCA1/2 mutation (BRCAm) and women with homologous-recombination deficiency (HRD). Adverse events (grade ≥ 3) were compared in all populations of the included studies.; Results: PARPi improved PFS significantly more than bevacizumab in women with a BRCAm (HR 0.47; 95% CI 0.36-0.60) and with HRD (HR 0.66; 95% CI 0.50-0.87). However, in the overall population with ovarian cancer, no significant difference in PFS was observed between women treated with PARPi and those treated with bevacizumab. PARPi exhibited the highest surface under the cumulative ranking probabilities value as the most effective treatment for PFS (PARPi vs. bevacizumab: 98% vs. 52% in the overall population with ovarian cancer; 100% vs. 50% in women with BRCAm; 100% vs. 50% in women with HRD). For adverse events, the risk of all treatments was similar. However, PARPi had a higher adverse risk than the control group (relative risk 2.14; 95% CI 1.40-3.26).; Conclusions: In women with newly diagnosed ovarian cancer, PARPi might be more effective in terms of PFS compared to bevacizumab. The risk of serious adverse events was similar for PARPi and bevacizumab. (© 2022. The Author(s).)

Suhaniya, S., et al. (2021). "Does insulin sensitisation improve metabolic and reproductive profiles in women with polycystic ovary syndrome who have overweight or obesity? A meta-analysis."
	
Sukan, B., et al. (2022). "Effect of Antioxidant Supplementation on Endometriosis-Related Pain: A Systematic Review." Current nutrition reports 11(4): 753-764.
	Purpose of Review: This study was conducted to determine the effects of antioxidant supplementation on endometriosis-related chronic pelvic pain, dysmenorrhea, and dyspareunia.; Methods: PubMed/MEDLINE, Scopus, and Cochrane Library databases and the Google Scholar search engine were searched from early 2012 to 2022 using appropriate keywords for clinical trials receiving antioxidant supplements and reporting endometriosis-related pelvic pain (PROSPERO registration number CRD42022318924). The qualities of the included studies were evaluated using the Joanna Briggs Institute (JBI) Checklists Critical Appraisal Tools and the National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study with no control group. This systematic review was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline.; Results: In this systematic review, 8 studies (5 RCTs and 3 non-comparative trials) published in 2012-2022 were included.; Conclusions: The studies we included showed promising results in the use of antioxidants in endometriosis-related pain. However, many scientific studies are needed for clear statements. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sukgen, G., et al. (2021). "Effects of mesh surgery on sexual function in pelvic prolapse and urinary incontinence." International braz j urol : official journal of the Brazilian Society of Urology 47(1): 82-89.
	PURPOSE: We aimed to determine pre-operative and post-operative sexual function scores of patients who underwent four-arm polypropylene mesh implantation surgery to treat urinary incontinence and pelvic organ prolapse. MATERIALS AND METHODS: A prospective study from January 2011 to November 2015 including patients (n: 72) submitted to surgical mesh implantation (four-arm anterior mesh implant (Betamix POP4R, Betatech Medical, Turkey) questioned the patients with Female Sexual Function Index evaluation form. The questionnaire was applied to all patients at pre-operative, post-operative 3rd month and post-operative 1st year periods. RESULTS: The mean age of the patients was 47.2±7.1 years. The mean Body Mass Index (kg/m2) was 28.7±3.7. The average of incontinence duration (year) was 4.6±2.6 and the average for operation time (min) was 35.7±2.1. After the urinary incontinence and pelvic organ prolapse surgery, it was observed that incontinence complaints of patients reduced. Furthermore, there was a positive change in quality of life and sexual function of patients at the post-operative period. There was a statistically significant increase according to Female Sexual Function Index score among all three periods (16%, 86% and 100% respectively, p=0.001) and improvement of sexual functions was observed. CONCLUSIONS: Transvaginal mesh use in the surgical treatment of pelvic organ prolapse improves quality of life. However, risk factors such as transvaginal mesh usage indication, surgical technique and experience of the surgeon, suitability of the material, the current health status of the patient and postoperative personal care of the patient may affect the success of operations.

Sukhikh, S., et al. (2023). "Safety and Efficacy of Transobturator Adjustment- Controlled Tape in the Treatment of Stress Urinary Incontinence at 5-Year Follow-up." Journal of Endourology 37(Supplement 1): A230.
	Introduction: Currently, suburethral slings are the standard of surgical treatment for stress urinary incontinence in women, which is very efficient, but also has several possible postoperative complications. Long-term performance of mid-urethral slings are scarcely studied. Method(s): The mid-urethral synthetic tape with tension control mechanism (MUS - TC) was developed as a polyvinyldinfluoride tape with absorbable collagen 5mm thick damping layer at mid-urethral part. A prospective randomized trial initiated in 2018 showed a high efficacy and safety profile of this device. In the analysis of the results one year after surgery, the efficiency of surgical treatment was 96%, the rate of postoperative complications, infravesical obstruction, was 2%, and the de novo urgency was 6%. In the present study we evaluated long-term outcomes (more than 5 years) by means of a telephone survey and validated questionnaires (UDI-6, IIQ-7) among patients who underwent MUS - TC. The study registered in ClinicalTrials.gov No. NCT04101279. Result(s): The average score on the UDI-6 survey was 1,22 +/- 0,81 and 1,2 +/- 0,77 on the IIQ-7 survey. There was a non-significant increase of scores after 60 months compared to 12 months after surgery. When analyzing individual clinical cases after 60 months, 10 patients noted worsening of symptoms. Of them, 6 patients noted recurrence of urinary incontinence when coughing or exercising. Accordingly, the subjective efficacy of surgical treatment during the 5-year follow-up period was 88%. Conclusion(s): The efficacy and safety data in the mid-term follow- up of patients after MUS - TC are comparable with the worldwide data. However, further long-term follow-up of the patients is required.

Şükür Yavuz, E., et al. (2023). "Impact of an estrogen replacement regimen on live birth rate in frozen-thawed good-quality embryo transfer." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 160(3): 829-835.
	Objective: To assess the impact of an estrogen replacement regimen on frozen embryo transfer (FET) cycle outcome.; Methods: In the present retrospective cohort study, data of infertile women undergoing FET with good-quality embryos were reviewed. The first group received 2 mg of estradiol hemihydrate (EH) once daily for 6 to 7 days, then twice daily for 4 to 5 days, and then three times a day until embryo transfer. The second group received EH twice daily for 7 to 8 days, then three times a day. The third group received EH three times a day constantly. The main outcome measure was live birth rate.; Results: In total, 394 FET cycles were included. The fixed 6-mg group required the highest estradiol hemihydrate dose. The duration of estrogen treatment was significantly longer in the first group. Maximal endometrial thickness was highest in the second group (10.2 ± 1.3 mm vs. 9.6 ± 1.4 mm vs. 8.6 ± 0.9 mm, respectively; P < 0.001). The clinical pregnancy rates in the groups were 41.1%, 55.2%, and 42.2%, respectively (P = 0.035). Live birth rates were 40.8%, 50.9%, and 48.1%, respectively (P = 0.320).; Conclusion: In FET cycles with hormone replacement therapy, a step-up 4-mg regimen provides thicker endometrium with optimal-dose estrogen in an adequate time frame. The tendency for increased clinical pregnancy and live birth rates is remarkable. (© 2022 International Federation of Gynecology and Obstetrics.)

Sulochana, M. and S. R. Sharma (2022). "Comparative Study of Laparoscopic Assisted Vaginal Hysterectomy Versus Total Abdominal Hysterectomy in Benign Gynecological Conditions." European Journal of Molecular and Clinical Medicine 9(4): 965-972.
	INTRODUCTION: The term "hysterectomy" though means removal of uterus, in practice it has a much wider classification depending upon the indication. At times, it is done without removal of cervix (supracervical hysterectomy) or with removal of adnexa (hysterectomy with salpingooopherectomy). It can also be a part of staging laparotomy or radical hysterectomy. Hysterectomy can be performed abdominally, vaginally or through abdominal ports with the help of laparoscope. MATERIALS AND METHODS: This is a Prospective and Comparative Study conducted at Department of Obstetrics and Gynecology in the Department of Obstetrics and Gynaecology, Ayaan Institute of Medical Sciences over a period of 1 year. Total 100 patients undergoing hysterectomy for benign uterine pathology meeting the inclusion and exclusion criterion will be included in the study. 50-Laparoscopic assisted vaginal hysterectomy and 50-Total abdominal hysterectomy. RESULT(S): 95% of women of TAH group needed spinal anesthesia and only 5% needed general anaesthesia. On the other hand all the women of LAVH group needed general anaesthesia. Duration of surgery was little more in patients who underwent LAVH when compared to patients who underwent TAH. The average duration of surgery in TAH group is 50 minutes and it is 75 minutes in LAVH group. Only 2 patients in LAVH group needed conversion into laparotomy because of adhesions and uncontrollable haemorrhage. Fever and wound infection was more with TAH group 11.6% compared to LAVH group 5% and 3.3%. UTI was also comparatively more with TAH group., which was the reason for longer hospital stay in TAH group. RTI was observed in 3 patients of LAVH group. CONCLUSION(S): LAVH is associated with less blood loss and decreased intra operative complications when compared to TAH. Length of hospital stay is significantly less for LAVH when compared to TAH. Post-operative pain, complications and blood transfusions are more with TAH group, because of which patient had longer hospital stay and took longer time for recovery and return to work.Copyright © 2022 Ubiquity Press. All rights reserved.

Sultan, M. I., et al. (2024). "Impact of a Mediterranean diet on prevention and management of urologic diseases." BMC Urology 24(1): 48.
	Compared to a Western diet, the Mediterranean diet moves away from red meat and processed foods. Universally regarded as a healthier dietary alternative, the Mediterranean diet has garnered scientific endorsement for its ability to confer an array of compelling benefits. These health benefits encompass not only a lowered incidence of Type 2 diabetes with a reduction in obesity, but also a robust protective effect on cardiovascular health. Extensive literature exists to corroborate these health benefits; however, the impact of a Mediterranean diet on urologic diseases, specifically sexual dysfunction, lower urinary tract symptoms, stone disease, and urologic cancers are not well studied. Understanding how dietary habits may impact these urologic conditions can contribute to improved prevention and treatment strategies. A total of 955 papers from PubMed and Embase were systematically reviewed and screened. After exclusion of disqualified and duplicated studies, 58 studies consisting of randomized controlled trials, cohort studies, cross sectional studies, reviews and other meta-analyses were included in this review. 11 primary studies were related to the impact of a Mediterranean diet on sexual dysfunction, 9 primary studies regarding urinary symptoms, 8 primary studies regarding stone disease, and 9 primary studies regarding urologic cancers. All primary studies included were considered of good quality based on a New-Castle Ottawa scale. The results demonstrate a Mediterranean diet as an effective means to prevent as well as improve erectile dysfunction, nephrolithiasis, lower urinary tract symptoms, and urinary incontinence. The review highlights the need for additional research to study the impact of diet on urologic cancers and other urologic conditions such as premature ejaculation, loss of libido, female sexual dysfunction, and overactive bladder.Copyright © The Author(s) 2024.

Sultana, A., et al. (2022). "A Systematic Review and Meta-Analysis of Premenstrual Syndrome with Special Emphasis on Herbal Medicine and Nutritional Supplements." Pharmaceuticals 15(11): 1371.
	Herbal medicine and nutritional supplements are suggested to treat premenstrual somatic and psycho-behavioural symptoms in clinical guidelines; nonetheless, this is at present based on poor-quality trial evidence. Hence, we aimed to design a systematic review and meta-analysis for their effectiveness in alleviating premenstrual symptoms. The published randomized controlled trials (RCTs) were extracted from Google scholar, PubMed, Scopus and PROSPERO databases. The risk of bias in randomized trials was assessed by Cochrane risk-of-bias tool. The main outcome parameters were analysed separately based on the Premenstrual Symptom Screening Tool and PMTS and DRSP scores. Secondary parameters of somatic, psychological, and behavioural subscale symptoms of PSST were also analysed. Data synthesis was performed assuming a random-effects model, and standardized mean difference (SMDs) was analysed using SPSS version 28.0.0 (IBM, Armonk, NY, USA). A total of 754 articles were screened, and 15 RCTs were included (n = 1211 patients). Primary results for participants randomized to an intervention reported reduced PSST (n = 9), PMTS (n = 2), and DSR (n = 4) scores with (SMD = -1.44; 95% CI: -1.72 to -1.17), (SMD = -1.69; 95% CI: -3.80 to 0.42) and (SMD = 2.86; 95% CI: 1.02 to 4.69) verses comparator with substantial heterogeneity. Physical (SMD = -1.61; 95% CI = -2.56 to -0.66), behavioural (SMD = -0.60; 95% CI = -1.55 to 0.35) and mood (SMD = 0.57; 95% CI = -0.96 to 2.11) subscale symptom groupings of PSST displayed similar findings. Fifty-three studies (n = 8) were considered at low risk of bias with high quality. Mild adverse events were reported by four RCTs. Based on the existing evidence, herbal medicine and nutritional supplements may be effective and safe for PMS.Copyright © 2022 by the authors.

Sultana, A., et al. (2022). "Role of Inflammation, Oxidative Stress, and Mitochondrial Changes in Premenstrual Psychosomatic Behavioral Symptoms with Anti-Inflammatory, Antioxidant Herbs, and Nutritional Supplements." Oxidative medicine and cellular longevity 2022: 3599246.
	Premenstrual syndrome (PMS) significantly lowers the quality of life and impairs personal and social relationships in reproductive-age women. Some recommendations are that inappropriate oxidative stress and inflammatory response are involved in PMS. Various nutritional supplements and herbs showed neuro-psycho-pharmacological activity with antioxidant and anti-inflammatory properties. This study aims to determine the systematic review of randomized controlled trials (RCTs) of herbal medicine and nutritional supplements in PMS. We also comprehensively highlighted the role of oxidative stress, inflammation, and mitochondrial changes on PMS with the application of computational intelligence. We used PRISMA and research question-based techniques to collect the data for evaluation of our study on different databases such as Scopus, PubMed, and PROSPERO from 1990 to 2022. The methodological quality of the published study was assessed by the modified Jadad scale. In addition, we used network visualization and word cloud techniques to find the closest terms of the study based on previous publications. While we also used computational intelligence techniques to give the idea for the classification of experimental data from PMS. We found 25 randomized controlled studies with 1949 participants (mean ± SD: 77.96 ± 22.753) using the PRISMA technique, and all were high-quality studies. We also extracted the closest terms related to our study using network visualization techniques. This work has revealed the future direction and research gap on the role of oxidative stress and inflammation in PMS. In vitro and in vivo studies showed that bioactive molecules such as curcumin, allicin, anethole, thymoquinone, cyanidin 3-glucoside, gamma-linoleic acid, and various molecules not only have antioxidant and anti-inflammatory properties but also other various activities such as GABA-A receptor agonist, serotonergic, antidepressant, sedative, and analgesic. Traditional Unani Herbal medicine and nutritional supplements can effectively relieve PMS symptoms as they possess many bioactive molecules that are pharmacologically proven for the aforementioned properties. Hence, these biomolecules might influence a complex physical and psychological disease process like PMS. However, more rigorous research studies are recommended for in-depth knowledge of the efficacy of bioactive molecules on premenstrual syndrome in clinical trials.; Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study. (Copyright © 2022 Arshiya Sultana et al.)

Sultana, F., et al. (2023). "Effect of dehydroepiandrosterone therapy on cognitive performance among postmenopausal women: a systematic review of randomized clinical trial data." Menopause (New York, N.Y.) 30(11): 1167-1173.
	Importance: Whether dehydroepiandrosterone (DHEA) supplementation improves cognitive performance in older women is uncertain. Nonetheless, DHEA supplements are readily available over the counter in several countries and are potentially being used to prevent cognitive decline and dementia.; Objective: This systematic review was conducted to evaluate the effect of exogenous DHEA on cognitive performance in postmenopausal women.; Evidence Review: Ovid MEDLINE, EMBASE, PsycINFO, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials databases were searched for studies of postmenopausal women until November 30, 2022. Eligible studies were required to be randomized clinical trials, be at least single blind, have a placebo or comparator arm and published in English. Risk of bias of the included studies was assessed by the revised Cochrane risk-of-bias tool.; Findings: Of the 15 articles retrieved for full-text review, four met the inclusion criteria. In all studies DHEA was administered as a 50-mg oral daily dose and all were double blind with an identical placebo. Three were placebo-controlled, crossover studies and one was a parallel-group clinical trial. The only positive outcome was limited to a 4-wk cross-over study in which DHEA statistically significantly enhanced five of six tests of visual-spatial performance compared with placebo in 24 cognitively normal postmenopausal women. Improvement in cognitive performance with DHEA treatment over placebo group was not seen in any other study. Heterogeneity of design and use of multiple measures of cognitive performance was a barrier to meta-analysis and between study comparisons. The studies were limited by high risk of bias in multiple domains.; Conclusion and Relevance: Overall, this systematic review does not support a beneficial effect of DHEA therapy on cognitive performance in postmenopausal women.; Competing Interests: Financial disclosures/Conflicts of interest: S.R.D. has been paid for developing and delivering educational presentations for Besins Healthcare, Biosyent and Abbott, has been on Advisory Boards for Astellas Pharma, Theramex, Mayne Pharma, Gedeon Richter and Roche Diagnostics, been a consultant to Lawley Pharmaceuticals and Que Oncology and has received institutional grant funding from Que Oncology and Ovocabio. R.M.I. has received support from Lawley Pharmaceuticals for conference attendance. (Copyright © 2023 by The Menopause Society.)

Sumanta, S. and S. Sujata (2022). "The role of dietary supplements on anthropometric indices and metabolism of glucose and lipid in polycystic ovarian syndrome: A systematic review and network-meta-analysis of randomized controlled studies."
	
Suminokura, J., et al. (2022). "Potential efficacy of weekly low-dose administration of bevacizumab as a combination therapy for platinum-resistant ovarian carcinoma: a retrospective analysis." BMC Cancer 22(1): 176.
	Background: Bevacizumab (Bev) plays the central role of the adjuvant therapy for patients with ovarian carcinoma. The aim of our study was to examine whether differences in the administration of Bev influence the prognosis of patients.; Methods: Patients with ovarian carcinoma who received treatment at two hospitals between 1999 and 2020 were identified. Patients treated with weekly low-dose administration of Bev (100 mg Bev on days 1 and 8 and 200 mg Bev on day 15, monthly) at one hospital (group A) and those with monthly high-dose administration of Bev (15 mg/kg of Bev on day 1, monthly) at another hospital (group B) were retrospectively compared.; Results: Among the total patients, 44 were assigned to group A and 33 were assigned to group B. More patients in group A had advanced disease (p = 0.03) and a lower dose of Bev at the first time during the first cycle administration (p < 0.01) than in group B. Progression-free survival (PFS) was better in group A than in group B (p < 0.01). Multivariate analysis revealed that group A was a better prognostic factor for PFS (hazard ratio 0.53, p = 0.03). Stable duration was longer in group A than in group B (p < 0.01). The incidences of adverse effects, including hematological toxicities such as neutropenia (p = 0.01) and nonhematological toxicities such as hypertension (p < 0.01), intestinal obstruction (p < 0.01), and thromboembolic events (p < 0.01), were lower in group A than in group B.; Conclusions: Weekly low-dose administration of Bev might improve prognosis and decrease the frequency of adverse effects associated with this drug although the prospective study was needed to get corroboration. (© 2022. The Author(s).)

Summey, R., et al. (2023). "Survival differences by race and surgical approach in early-stage operable cervical Cancer." Gynecologic Oncology 179: 63-69.
	Objective: To evaluate if the higher rate of open radical hysterectomy in Black patients, prior to the widespread return to open surgical techniques, mitigated survival disparities and to identify other actionable factors to target for systemic change. Method(s): This is a retrospective cohort study including patients from the National Cancer Database with cervical cancer who underwent radical hysterectomy from 2010 to 2018. Patient demographics, clinical characteristics and survival were compared by race and surgical route. Kaplan-Meier plots were constructed. Cox proportional hazards modeling was used to adjust for covariates. Result(s): 7201 patients were eligible for inclusion, 687 (9.5%) Black and 4870 (68%) White. We found that 51% of Black patients and 39% of White patients underwent open surgery. Black patients were 10% less likely to receive Guideline Concordant Care (GCC). Those with publicly-funded insurance had a 40% higher hazard of death compared to private insurance (CI 1.19-1.73 p < 0.001). Black patients who had open surgery had similar 5-year survival compared to White patients who had MIS surgery (0.90 vs 0.91, NS). After adjusting for potential confounders including age, insurance, nodal status, and lymphovascular space invasion, Black patients who had surgery had a 40% higher hazard for death (HR 1.40 95% CI 1.10-1.79, p = 0.007) compared to White patients. Conclusion(s): A lower 5 and 10-year survival was seen in Black patients, regardless of surgical approach. Adjustment for significant covariates did not resolve this disparity, confirming that these factors do not fully account racial disparities.Copyright © 2023 Elsevier Inc.

Sun, C.-Y., et al. (2023). "Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis." Journal of integrative medicine 21(5): 455-463.
	Background: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.; Objective: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.; Search Strategy: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.; Inclusion Criteria: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.; Data Extraction and Analysis: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.; Results: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.; Conclusion: Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Sun, D., et al. (2022). "Is there a place for Traditional Chinese Medicine (TCM) in the treatment of recurrent pregnancy loss?" Journal of Reproductive Immunology 152: 103636.
	Recurrent pregnancy loss (RPL) impacts a couple's quality of life, mental health and constitutes a large economic burden for care. Traditional Chinese Medicine (TCM) is an integrated systematic medical practice with wide clinical applications that has been predominantly used throughout Asian countries for over 2000 years. However, the efficacy of TCM in the treatment of RPL remains unclear due not only to a lack of experimental evidence, but also a lack of comprehensive summarized conclusions. Therefore, the current manuscript reviews recent relevant publications of the clinical use of TCM in RPL and illustrates its potential mechanisms. All publications (in both Chinese and English), especially randomized controlled trials (RCTs), on the use of TCM in RPL for the last ten years and research on its mechanisms were included. This review also describes our understanding of the problems and challenges in the modernization of TCM research. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sun, H., et al. (2022). "Ovarian reserve and IVF outcomes in patients with inflammatory bowel disease: A systematic review and meta-analysis." EClinicalMedicine 50: 101517.
	Background: Inflammatory bowel disease (IBD) mainly affects people during reproductive age. However, it is unclear whether IBD might be associated with impaired ovarian reserve in female patients or with in vitro fertilization (IVF) outcomes. Method(s): This systematic review and meta-analysis included articles from inception to May, 2022. Random-effect model was applied to calculate the standardized mean differences (SMDs) and odds ratios (ORs) and their 95% confidence intervals (95%CIs). Studies comparing the ovarian reserve or IVF outcomes of patients with IBD with the population were considered. To be included in this study, necessary measurements such as OR, relative risk (RR), SMD or hazard ratio (HR) or any necessary information to calculate them were provided in the articles. Letters, case reports, review articles including meta-analyses and expert opinions were excluded. For different articles studying the same population, the article with larger scale was selected. Finding(s): We included in our analysis 9 studies and data from 2386 IBD records and matched controls. Comparing with women without IBD, women with IBD had lower anti-mullerian hormone (AMH) levels (SMD = -0.38, 95%CI: -0.67, -0.09); (I2 = 79.0%, p = 0.000). Patients with IBD of different ages showed distinct ovarian reserves, with patients below 30 years old not showing any decline in ovarian reserve compared to the control group (SMD = -0.56, 95%CI: -2.28, 1.16); (I2 = 96.3%; p = 0.000), while patients with IBD over 30 years old (SMD = -0.75, 95%CI: -1.07, -0.43); (I2 = 0.0%; p = 0.608) showed a decline compared to control group. Patients with IBD in remission stage had similar ovarian reserves to population (SMD = -0.10, 95%CI: -0.32, 0.12); (I2 = 0.0%; p = 0.667), while patients in active stage showed an impaired ovarian reserve (SMD = -1.30, 95%CI: -1.64, -0.96); (I2 = 0.0%; p = 0.318). Patients with IBD showed a pregnancy rate after receiving IVF treatment comparable to the control population (OR = 0.87, 95%CI: 0.55, 1.37); (I2 = 70.1%, p = 0.035). Interpretation(s): The result of this study suggest that IBD may reduce reproductive age women's ovarian reserve and IVF treatment might help pregnancy outcomes in patients with impaired fertility. These results should be further validated in additional studies given the heterogeneity and quality of the studies included. Funding(s): This study was supported by the National Natural Science Foundation of China (No. 81671423), National Key Research and Development Program of China (No. 2016YFC1000603), 2020 Shenyang Science and Technology Plan Program (No. 20-205-4-006), Scientific and Technological Talents Applied Technology Research Program of Shenyang (No. 18-014-4-56).Copyright © 2022 The Author(s)

Sun, H., et al. (2023). "Dosimetry study of Auto-VMAT planning and Manual-VMAT planning based on Pinnacle39.10 in radiotherapy for cervical cancer." Medicine (United States) 102(26): E34129.
	The purpose of this study was to compare the dose distribution characteristics of automatic volume-modulated arc therapy (Auto-VMAT) planning and manual volume-modulated arc therapy (Manual-VMAT) planning of Philips Pinnacle39.10 planning system, to provide a basis for optimal radiation therapy planning for cervical cancer. Ten patients with cervical cancer in our hospital from September to December 2018 were selected, and 2 treatment plans, Auto-VMAT plan and Manual-VMAT plan, were designed using Pinnacle39.10 planning system, respectively, to evaluate the maximum dose Dmax, mean dose Dmean, homogeneity index of the target area according to the dose volume histogram, the conformability index, plan optimization time, monitor units (MUs), organ at risk and other indicators. The results were that the Auto-VMAT plan was superior to the Manual-VMAT plan for target area Dmean, conformability index, and homogeneity index, with statistically significant differences (P <.05) and no significant difference in maximum dose Dmax (P >.05); rectal V40, V50, and Dmean in the Auto-VMAT plan, bladder V40, V50, and Dmean, small bowel V30, V40, V50 and Dmean, and right and left femoral V50 and Dmean were all lower than the Manual-VMAT plan, and the difference was statistically significant (P <.05); the mean optimization time for the Auto-VMAT and Manual-VMAT plans was 47 minutes and 35 minutes, respectively, an increase of 34%. The average number of MUs was 519 MUs and 374 MUs, respectively, an increase of 28%. This study concluded that the Pinnacle39.10-based Auto-VMAT plan was clinically feasible and significantly superior to the Manual-VMAT plan in terms of improved target area uniformity and conformability and reduced organ endangerment dose while reducing the impact of human factors on the quality of plan design.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Sun, H., et al. (2023). "OS and DFS are affected by different diagnostic methods and hysterectomy procedures in endometrial cancer patients: A single-center retrospective study." Cancer Medicine 12(18): 19072-19080.
	Purpose: We aimed to evaluate whether hysteroscopy increases the risk of intraperitoneal dissemination or worsens the prognosis of endometrial carcinoma (EC) patients and whether radical hysterectomy (RH) improves overall survival (OS) or disease-free survival (DFS) in patients with stage II to III EC and to investigate the effects of different procedures for identifying EC and the effects of different surgical methods on the OS and DFS of endometrial cancer patients. Method(s): Four hundred sixty-five women with EC were included in this retrospective study. Log-rank tests and Kaplan-Meier analysis were used for the outcome comparisons of the effects of the EC diagnostic method and different hysterectomy procedures. A Cox proportional hazards model was used for univariate regression analysis. Result(s): Among the three procedures for diagnosing EC (diagnostic curettage, hysteroscopy, and hysterectomy), the incidences of fallopian tube and ovarian invasion were not significantly different (p = 0.506 and 0.066, respectively). The diagnostic methods for EC had no significant effect on OS (p = 0.577) or DFS (p = 0.294). In addition, type II RH and type III RH did not improve the prognosis of patients with FIGO stage II and III disease (log-rank p = 0.914 and 0.810 for OS; log-rank p = 0.707 and 0.771 for DFS, respectively). Conclusion(s): Based on the current study evidence, the use of diagnostic hysteroscopy procedures is safe and does not increase the risk of fallopian tube and ovarian invasion of intraperitoneal dissemination or worsen the prognosis of EC patients. Type II and type III RH did not demonstrate a benefit for stage II-III EC patients.Copyright © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Sun, H.-N., et al. (2022). "Ethyl β-Carboline-3-Carboxylate Increases Cervical Cancer Cell Apoptosis Through ROS-p38 MAPK Signaling Pathway." In vivo (Athens, Greece) 36(3): 1178-1187.
	Background/aim: Ethyl β-carboline-3-carboxylate (β-CCE) is one of the effective ingredients of Picrasma quassioides (P. quassioides). As a β-carboline alkaloid, it can antagonize the pharmacological effects of benzodiazepines by regulating neurotransmitter secretion through receptors, thus affecting anxiety and physiology. However, its efficacy in cancer treatment is still unclear.; Materials and Methods: We explored the effect of b-CCE on SiHa cells using MTT assay, western blot, flow cytometry, LDH release, T-AOC, SOD, and MDA assays.; Results: We investigated the cytotoxicity of β-CCE in SiHa cells and verified that β-CCE could induce cell apoptosis in a time- and concentration-dependent manner. In this process, treatment with β-CCE significantly increased the levels of cytoplasmic and mitochondrial reactive oxygen species (ROS), which disturb the oxidation homeostasis by regulating the total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) production. Notably, the addition of N-acetylcysteine (NAC) (ROS scavenger) effectively alleviated β-CCE-induced apoptosis in SiHa cells. In addition, β-CCE might activate the p38/MAPK signaling pathway, as the pre-treatment with SB203580 (p38 inhibitor) significantly reduced β-CCE-induced apoptosis in SiHa cells.; Conclusion: β-CCE has an anti-tumor activity. It activates the p38/MAPK signaling pathway by increasing intracellular ROS levels, which subsequently induce SiHa cell apoptosis. Our results provide a novel therapeutic target for treatment of cervical cancer. (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Sun, J., et al. (2023). "Relationship between anxiety and depressive trajectories of women who conceived through assisted reproductive technology and their children's emotional and behavioral problems: A prospective cohort study." Journal of Affective Disorders 332: 150-158.
	Objective: This study aimed to examine the relationship between the anxiety and depressive trajectory of women conceived through assisted reproductive technology (ART) and their children's emotional and behavioral problems.; Methods: This prospective cohort study including 18,711 women, was conducted between July 2014 and December 2017. Self-rating scales for anxiety and depression were used before treatment, during the first trimester, and two to three years postpartum. A latent class growth analysis identified their maternal anxiety and depressive symptom trajectories. Multiple comparison and linear regression models were performed to assess the relationships between maternal trajectories and their offspring's emotional and behavioral problems.; Results: Three longitudinal heterogeneous trajectories of maternal anxiety and depressive symptoms were identified: resilient, recurrent, and emergent. After adjusting for covariates, children with mothers in the recurrent and emergent trajectory groups had higher Child Behavior Checklist/2-3 scores. Additionally, the participants with a recurrent trajectory had lower education and employment levels and younger maternal age at delivery. They also had a history of ovarian surgery, primipara, secondary infertility, polycystic ovary syndrome, and more embryo transferred cycles, including intracytoplasmic sperm injections. Those with resilient trajectories had higher antral follicle counts and GnRH antagonist protocol. Finally, the participants with emergent trajectories had a lower monthly income, primipara, ectopic pregnancy, and fresh embryo transfers.; Conclusions: Infertile women's psychological stress was not alleviated by the ART-sociodemographic, infertility-related and treatment-related characteristics determined three mental health trajectories. Children with mothers in recurrent and emergent trajectories showed higher odds of experiencing emotional and behavioral problems.; Competing Interests: Conflict of interest The authors declare no conflict of interest. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sun, J., et al. (2021). "Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: an update evidence from 14 studies." BMC Cancer 21(1): 618.
	Background: CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects. Method(s): We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab. Result(s): When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade >= 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade >= 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393-0.469) and 1.060 months (95% CI: 1.043-1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022-0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively. Conclusion(s): Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.Copyright © 2021, The Author(s).

Sun, M., et al. (2022). "Effect of opioids on cancer survival in patients with chronic pain: a propensity score-matched population-based cohort study." British Journal of Anaesthesia 128(4): 708-717.
	Background: The impact of opioid analgesic use before cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare overall and cancer-related survival of patients with chronic pain who received long-term opioid analgesic treatment with that of those who did not receive such treatment. Method(s): We included patients with chronic pain and categorised them into the following two groups according to their analgesic use: patients with cancer and chronic pain who were prescribed >=180 defined daily doses of opioid analgesics per year >3 months before cancer diagnosis comprised the case group, and those who were prescribed <28 defined daily doses of opioid analgesics per year before cancer diagnosis comprised the control group. Patients in both groups were matched at a ratio of 1:5. The primary outcome was overall long-term survival. Result(s): The matching process yielded a final cohort of 1716 patients (286 and 1430 in the case and control groups, respectively) who were eligible for further analysis. The adjusted hazard ratio for overall survival in patients receiving long-term opioids was 3.53 (95% confidence interval: 3.03-4.11; P<0.001). Conclusion(s): Long-term opioid analgesic use before cancer diagnosis might be associated with poor overall survival in patients with chronic pain compared with such patients who did not receive long-term opioid analgesics.Copyright © 2022 British Journal of Anaesthesia

Sun, R., et al. (2023). "Comparing Short- and Long-Term Treatment Duration of Bevacizumab for Advanced Ovarian Cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(10): 1952-1953.
	
Sun, S., et al. (2022). "A meta-analysis of survival after minimally invasive radical hysterectomy versus abdominal radical hysterectomy in cervical cancer: center-associated factors matter." Archives of Gynecology and Obstetrics 306(3): 623-637.
	Purpose: To explore the possible factors that contributed to the poor performance of minimally invasive surgery (MIS) versus abdominal surgery regarding progression-free survival (PFS) and overall survival (OS) in cervical cancer.; Methods: MEDLINE, EMBASE, Cochrane Library and Web of Science were searched (January 2000 to April 2021). Study selection was performed by two researchers to include studies reported oncological safety. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were combined using random-effect model. Subgroup analyses were stratified by characteristics of disease, publication, study design and treatment center.; Results: Sixty-one studies with 63,369 patients (MIS 26956 and ARH 36,049) were included. The overall-analysis revealed a higher risk of recurrence (HR 1.209; 95% CI 1.102-1.327) and death (HR 1.124; 95% CI 1.013-1.248) after MIS versus ARH expect in FIGO IB1 (FIGO 2009 staging) patients with tumor size less than 2 cm. However, subgroup analyses showed comparable PFS/DFS and OS in studies published before the Laparoscopic Approach to Cervical Cancer (LACC) trial, published in European journals, conducted in a single center, performed in centers in Europe and in centers with high sample volume or high MIS sample volume.; Conclusion: Our findings highlight possible factors that associated with inferior survival after MIS in cervical cancer including publication characteristics, center-geography and sample volume. Center associated factors were needed to be taken into consideration when evaluating complex surgical procedures like radical hysterectomy. (© 2022. The Author(s).)

Sun, S., et al. (2022). "Anlotinib plus chemoradiotherapy in the treatment for FIGO stage IB3 and IIB-IVA cervical cancer: A prospective single-arm, single-center, exploratory phase II trial (299)." Gynecologic Oncology 166(Supplement 1): S157.
	Objectives: Cervical carcinoma is the fourth leading cause of cancer-related death among women worldwide. Previous randomized clinical trials showed a 30% to 50% decrease in risk of death in locally advanced cervical cancer (LACC) with the addition of concurrent platinum-based chemoradiotherapy when compared with radiotherapy alone. Mechanisms to account for improved efficacy are thought to include direct cytotoxicity, radiosensitization of tumor cells, and control of subclinical metastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib synergizes with radiation and cisplatin, as shown in preclinical and clinical studies. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to concurrent chemoradiotherapy in FIGO stage IB3 and IIB-IVA cervical cancer. Method(s): Inclusion criteria include treatment-naive histologically confirmed FIGO stage IB3 to IVA cervical cancer with at least one measurable lesion and ECOG performance score 0-2 within the age range of 18 to 75 years. Abundant organ functions are required, with no contraindication to anlotinib or chemoradiation present. Patients will be treated with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total 3 cycles) and X-ray external-beam radiotherapy (total 45Gy-50Gy in 25-28 fraction), followed by brachytherapy (6Gy/5 fractions or 7Gy/4 fractions) with concurrent cisplatin (40 mg/m2 weekly for 5-6 weeks). The primary endpoint is the progression-free survival (PFS) rate at three years. The secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and quality of Life (QOL). Safety will be evaluated in all patients who receive study drugs according to the treatment received (safety population) by recording clinical adverse events (AEs) using National Cancer Institute Common. The sample size calculation of 47 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test; considering a 10% reduction, a total of 53 samples are required. This study is currently open, and 23 patients have been enrolled. The estimated primary completion date is December 1, 2024, and the estimated study completion date is October 31, 2025.Copyright © 2022 Elsevier Inc.

Sun, T. T., et al. (2021). "Clinical Features and Long-Term Outcomes After Laparoscopic Surgery in Patients Co-existing With Endometriosis and Adenomyosis." Frontiers in Medicine 8: 696374.
	Objective: To investigate the difference of clinical features and outcomes between EM patients with and without AM after following up for at least 6 years after surgery. Methods: We retrospectively analyzed 358 EM patients who had a minimum of 6 years follow-up after laparoscopic cystectomy, which was performed by one single doctor at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into AM group and non-AM group and analysis was performed in preoperative characteristics, surgical findings and postoperative outcomes during follow-up. Results: A total of 358 EM patients were recruited, of which 142 (39.7%) were in the AM group and the rest 216 (60.3%) in the non-AM group. Between the two group, the mean age was 34.6 vs. 32.2 years (P < 0.001). The mean operating time in the AM and non-AM group was 73.2 vs. 61.9 min (P < 0.001). According to the revised AFS classification, the mean score of the two group were 60.3 vs. 45.5 (P < 0.001). At the end of the follow-up, though the AM group was with higher rate of disease relapse, yet no significant difference was found between the two groups in statistical comparison (34/142 [23.9%] vs. 34/216 [15.7%], P = 0.053). With a minimum follow-up of 6 years after laparoscopic cystectomy, failed and successful pregnancy were seen in 107/142(75.4%) and 35/142 (24.6%) patients in the AM group vs. 114/216(52.8%) and 102/216 (47.2%) patients in the non-AM group (P < 0.05). As for the successfully pregnant patients, live births, including spontaneous pregnancy and IVF-ET, were seen in 34/35 (97.1) vs. 99/102 (97.1) patients between AM and non-AM groups, while others ended in spontaneous abortion. No significant associations were found between the two groups in infertility, leiomyoma presence, the size of ovarian endometrioma, type of deep infiltrating endometriosis (DIE) or type of recurrence (P > 0.05). Conclusion: Compared with non-AM group, EM patients with concurrent AM may have higher age, longer mean operating time and higher mean AFS score. In terms of fertility outcomes, patients in the AM group were with lower likelihood of pregnancy after surgery during the long-time follow-up.

Sun, W., et al. (2021). "Gastrointestinal events with PARP inhibitors in cancer patients: A meta-analysis of phase II/III randomized controlled trials." Journal of Clinical Pharmacy and Therapeutics 46(2): 241-255.
	What Is Known and Objective: PARP inhibitors are currently one of the most promising PARP targeted drugs for patients with certain types of cancer. Gastrointestinal (GI) events are common adverse events for all PARP inhibitors. We conducted this meta-analysis of randomized controlled trials (RCTs) to fully investigate the incidence and the relative risk of GI events in cancer patients receiving PARP inhibitors.; Study Design: Randomized controlled trials in cancer patients treated with PARP inhibitors were retrieved, and the systematic evaluation was conducted. Embase and PubMed/Medline were searched for articles published till July 2020.; Results: Twenty-nine RCTs and 9529 patients were included. The present meta-analysis suggests that the use of PARP inhibitors significantly increases the risk of developing all-grade nausea (RR, 1.46; 95% CI, 1.29-1.66; p < .00001), vomiting (RR, 1.39; 95% CI, 1.17-1.64; p = .0001), diarrhoea (RR, 1.14; 95% CI, 1.06-1.23; p = .0003) and decreased appetite (RR, 1.24; 95% CI, 1.14-1.36; p < .00001), but not for constipation. And the use of these agents significantly increased the risk of high-grade nausea (RR, 1.99; 95% CI, 1.44-2.74; p < .0001), vomiting (RR, 1.54; 95% CI, 1.11-2.14; p = .01) and decreased appetite (RR, 2.03; 95% CI, 1.22-3.40; p = .007), except for diarrhoea and constipation. Nausea was the most common GI event for these agents. Patients receiving veliparib were associated with a relatively lower risk of all-grade nausea and vomiting. Patients with ovarian cancer tend to have a higher risk of all-grade nausea and vomiting than those with non-ovarian cancer. The risk of all-grade nausea and vomiting tended to be higher when PARP inhibitors treatment was longer.; What Is New and Conclusion: PARP inhibitors were associated with a significant increased risk of GI events. Clinicians should be aware of these risks and perform regular monitoring. (© 2020 John Wiley & Sons Ltd.)

Sun, X., et al. (2023). "Effectiveness and safety of platelet rich plasma (PRP) in improving decreased ovarian reserve, primary ovarian insufficiency and ovarian aging: a systematic review and meta-analysis."
	
Sun, X. Y. and Z. Liang (2021). "Effect of drug therapy on pregnancy rate, sex hormone levels and adverse reactions after laparoscopic surgery in patients with endometriosis and infertility." Journal of Biological Regulators and Homeostatic Agents 35(1): 191‐196.
	
Sun, Y., et al. (2019). "Conservative interventions for the treatment of pelvic organ prolapse: A systematic review protocol." Medicine 98(47): e18116.
	Background: Pelvic organ prolapse (POP) is the downward descent of vaginal walls, affecting the health of 32% to 76% female patients. Conservative interventions are considered as priority before seeking help from surgery. We plan to make the systematic review to assess the effectiveness of conservative intervention for adult women with POP.; Methods: Studies will be searched in PubMed, EMBASE, and the Cochrane Library from inception to July 2017. Primary outcomes are specific POP-related symptom, severity of prolapse, Prolapse-related, and general health-related quality of life and other non-POP-specific symptoms.; Results: The data will be synthesized if possible using MD, SMD or RR. A descriptive analysis will be made if the data cannot be synthesized.; Discussion: The systematic review might provide solid evidence for the treatment of POP by conservative intervention.

Sun, Y., et al. (2020). "Levonorgestrel intrauterine system versus oral progestin for preventing the recurrence of endometrial polyps after hysteroscopic resection: A meta-analysis of 19 randomized controlled trials." Clinical and Experimental Obstetrics and Gynecology 47(6): 821-832.
	Background: The aim of this meta-analysis was to compare levonorgestrel intrauterine system (LNG-IUS) with oral progestin for preventing the recurrence of endometrial polyps after hysteroscopic resection. Material(s) and Method(s): Computerized literature search was performed in PubMed and several Chinese databases to screen for relevant trials. Quality assessment and meta-analysis were performed for the included trials. Result(s): A total of 19 randomized controlled trials were identified. Meta-analysis indicated that the LNG-IUS group was associated with lower recurrence rate of endometrial polyps than the oral progestin group (p < 0.0001), while there was no significant difference in the incidence of abnormal uterine bleeding between groups (p > 0.05). In terms of adverse effects related to progestin, the LNG-IUS group had significantly fewer adverse effects than the oral progestin group (p < 0.0001). Additionally, the LNG-IUS group had thinner endometrium and higher hemoglobin levels than the oral progestin group (p < 0.00001). Conclusion(s): The LNG-IUS was more effective and safer in preventing the recurrence of endometrial polyps after hysteroscopic resection than oral progestin.Copyright © 2020 Sun et al. Published by IMR Press.

Sun, Y., et al. (2024). "Whether surgical procedure can improve the prognosis of endometrial cancer arising in adenomyosis (EC-AIA)? a systematic review and meta-analysis." International journal of surgery (London, England).
	Purpose: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, we summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients.; Methods: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023.; Results: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan-Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy (P=0.016), but there was no difference in overall survival (OS). Univariable (P=0.025, HR=0.25, 95%CI=0.08-0.84) and multivariable (P=0.042, HR=0.13, 95%CI=0.020-0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS.; Conclusion: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Sun, Y., et al. (2023). "Association between urban green space and postpartum depression, and the role of physical activity: a retrospective cohort study in Southern California." Lancet Regional Health - Americas 21: 100462.
	Background: Little research exists regarding the relationships between green space and postpartum depression (PPD). We aimed to investigate the relationships between PPD and green space exposure, and the mediating role of physical activity (PA). Method(s): Clinical data were obtained from Kaiser Permanente Southern California electronic health records in 2008-2018. PPD ascertainment was based on both diagnostic codes and prescription medications. Maternal residential green space exposures were assessed using street view-based measures and vegetation types (i.e., street tree, low-lying vegetation, and grass), satellite-based measures [i.e., Normalized Difference Vegetation Index (NDVI), land-cover green space, and tree canopy cover], and proximity to the nearest park. Multilevel logistic regression was applied to estimate the association between green space and PPD. A causal mediation analysis was performed to estimate the proportion mediated by PA during pregnancy in the total effects of green space on PPD. Finding(s): In total, we included 415,020 participants (30.2 +/- 5.8 years) with 43,399 (10.5%) PPD cases. Hispanic mothers accounted for about half of the total population. A reduced risk for PPD was associated with total green space exposure based on street-view measure [500 m buffer, adjusted odds ratio (OR) per interquartile range: 0.98, 95% CI: 0.97-0.99], but not NDVI, land-cover greenness, or proximity to a park. Compared to other types of green space, tree coverage showed stronger protective effects (500 m buffer, OR = 0.98, 95% CI: 0.97-0.99). The proportions of mediation effects attributable to PA during pregnancy ranged from 2.7% to 7.2% across green space indicators. Interpretation(s): Street view-based green space and tree coverage were associated with a decreased risk of PPD. The observed association was primarily due to increased tree coverage, rather than low-lying vegetation or grass. Increased PA was a plausible pathway linking green space to lower risk for PPD. Funding(s):National Institute of Environmental Health Sciences (NIEHS;R01ES030353).Copyright © 2023 The Author(s)

Sun, Y., et al. (2021). "Clinical efficacy of levonorgestrel intrauterine system (Mirena) combined with hysteroscopy in the treatment of perimenopausal AUB patients." Pakistan journal of pharmaceutical sciences 34(5(Special)): 2079-2083.
	Perimenopausal abnormal uterine bleeding (AUB) is most common in ovulation dysfunction, which seriously compromises patients' health. This study aims to evaluate the efficacy of levonorgestrel intrauterine system (Mirena) plus hysteroscopy respectively in perimenopausal AUB. Sixty perimenopausal AUB patients treated with hysteroscopic electric resection in our hospital between January 2020 and December 2020 were enrolled and randomized to control group given dydrogesterone and study group treated with Mirena, with 30 cases in each group. The treatment efficacy, sex hormone level, hemoglobin (Hb) level, endometrial thickness and menstruation conditions were compared. The total efficacy was higher in the study group than that in the control group (P<0.05). The study group had lower follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and higher Hb levels compared with those of the control group (all P<0.05). Thinner endometrial thickness, lower pictorial blood loss assessment chart (PBAC) scores and shorter duration of menstruation were observed in the study group (all P<0.05). Both Mirena and dydrogesterone enhance the clinical efficacy of hysteroscopic treatment of perimenopausal AUB patients, with the advantages of Mirena being more promising.

Sun, Y. and F. Ren (2023). "Whether patients with endometrial cancer arising in adenomyosis (EC-AIA) should have supplementary lymphadenectomy? A systematic review and meta-analysis."
	
Sun, Y., et al. (2023). "The role of poly (ADP-ribose) glycohydrolase in phosphatase and tensin homolog deficiency endometrial cancer." The Journal of Obstetrics and Gynaecology Research 49(4): 1244-1254.
	Aim: To explore the relationship between poly(ADP-ribose) glycohydrolase (PARG) and the occurrence, development, and prognosis of endometrial carcinoma (EC), and investigate whether the PARG inhibitor PDD0017273 could increase the sensitivity of EC cells to cisplatin.; Methods: The expression of PARG, phosphatase and tensin homolog (PTEN), and p53 in normal endometrial tissues (NE), endometrial hyperplasia without atypia (EH), atypical endometrial hyperplasia (AH), and EC was detected by immunohistochemistry. AN3CA EC cells with PTEN deficiency were treated with different cisplatin and PDD0017273, alone or in combination. Cell proliferation was detected by MTT method, apoptosis was detected by flow cytometry, and the expression of PARG in EC cells after treatment with different drugs was detected by western blot and immunohistochemistry.; Results: Expression of PARG in NE, EH, AH, and EC increased gradually. In addition, compared with low PARG expression in PTEN-positive EC, patients who had high PARG expression in PTEN-negative EC had more advanced clinical stages (r = -0.399, p = 0.032) and shorter overall survival time (p = 0.037). A dose of 40 μM PDD0017273 effectively inhibited PARG expression, increased the sensitivity of AN3CA cells to cisplatin.; Conclusions: The findings suggest that PARG overexpression is a promising immunohistochemical marker to predict the occurrence and prognosis of EC. Moreover, PARG inhibition produced antitumor effects and increased the sensitivity of EC cells with PTEN deficiency to cisplatin. (© 2023 Japan Society of Obstetrics and Gynecology.)

Sundar, S., et al. (2022). "Quality of life from cytoreductive surgery in advanced ovarian cancer: Investigating the association between disease burden and surgical complexity in the international, prospective, SOCQER-2 cohort study." BJOG : an international journal of obstetrics and gynaecology 129(7): 1122-1132.
	Objective: To investigate quality of life (QoL) and association with surgical complexity and disease burden after surgical resection for advanced ovarian cancer in centres with variation in surgical approach.; Design: Prospective multicentre observational study.; Setting: Gynaecological cancer surgery centres in the UK, Kolkata, India, and Melbourne, Australia.; Sample: Patients undergoing surgical resection (with low, intermediate or high surgical complexity score, SCS) for late-stage ovarian cancer.; Main Outcome Measures: Primary: change in global score on the European Organisation for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire (QLQ-C30). Secondary: EORTC ovarian cancer module (OV28), progression-free survival.; Results: Patients' preoperative disease burden and SCS varied between centres, confirming differences in surgical ethos. QoL response rates were 90% up to 18 months. Mean change from the pre-surgical baseline in the EORTC QLQ-C30 was 3.4 (SD 1.8, n = 88) in the low, 4.0 (SD 2.1, n = 55) in the intermediate and 4.3 (SD 2.1, n = 52) in the high-SCS group after 6 weeks (p = 0.048), and 4.3 (SD 2.1, n = 51), 5.1 (SD 2.2, n = 41) and 5.1 (SD 2.2, n = 35), respectively, after 12 months (p = 0.133). In a repeated-measures model, there were no clinically or statistically meaningful differences in EORTC QLQ-C30 global scores between the three SCS groups (p = 0.840), but there was a small statistically significant improvement in all groups over time (p < 0.001). The high-SCS group experienced small to moderate decreases in physical (p = 0.004), role (p = 0.016) and emotional (p = 0.001) function at 6 weeks post-surgery, which resolved by 6-12 months.; Conclusions: The global QoL of patients undergoing low-, intermediate- and high-SCS surgery improved at 12 months after surgery and was no worse in patients undergoing extensive surgery.; Tweetable Abstract: Compared with surgery of lower complexity, extensive surgery does not result in poorer quality of life in patients with advanced ovarian cancer. (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Sunderam, S., et al. (2020). "Comparing fertilization rates from intracytoplasmic sperm injection to conventional in vitro fertilization among women of advanced age with non-male factor infertility: a meta-analysis." Fertility and Sterility 113(2): 354.
	Objective: To evaluate the effectiveness of intracytoplasmic sperm injection (ICSI) in improving fertilization rates compared to conventional in vitro fertilization rates (IVF) among women aged ≥38 years with a non-male factor diagnosis.; Design: Systematic review and meta-analysis.; Setting: Not applicable.; Patient(s): Women aged ≥38 years with a non-male factor diagnosis receiving IVF or ICSI.; Intervention(s): A systematic review of databases including PubMed and Embase was performed. Study protocol was registered at the International Prospective Register of Systematic Reviews. Studies were selected if they compared fertilization rates from ICSI with those from conventional IVF among women aged ≥38 years with a non-male factor infertility diagnosis. A random effects model was used. Meta-analysis of Observational Studies in Epidemiology guidelines were applied.; Main Outcome Measure(s): Fertilization rate.; Results: Seven studies including 8796 retrieved oocytes (ICSI: 4,369; IVF: 4,427) with mean female age ≥38 years met the inclusion criteria. There was no significant difference in fertilization rates between ICSI and conventional IVF (relative risk [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; P = .8). Heterogeneity was observed between studies (I 2 = 58.2; P < .05). Heterogeneity was significant (I 2 = 57.1; P < .05) when cycles with prior fertilization failure were excluded; however, when analysis was restricted to poor responders (RR 1.01, 95% CI 0.97-1.05; P = .6), heterogeneity was no longer significant (I 2 = 0.0; P = .5).; Conclusions: No difference was found in fertilization rates between conventional IVF and ICSI. Further studies are needed to assess the impact of ICSI in this population, controlling for other indications such as preimplantation genetic testing. (Published by Elsevier Inc.)

Sundström-Poromaa, I. and E. Comasco (2023). "New Pharmacological Approaches to the Management of Premenstrual Dysphoric Disorder." CNS drugs 37(5): 371-379.
	Premenstrual symptoms are experienced by many female individuals during their fertile age. Premenstrual dysphoric disorder (PMDD), a sex-specific mood disorder, affects about 5% of female individuals during the luteal phase of the menstrual cycle. Treatment with selective serotonin reuptake inhibitors represents a valid solution to manage PMDD for many, but not all, patients. Owing to maladaptive neural reactivity to gonadal hormone fluctuations, that is, the putative mechanism postulated to underlie PMDD, drugs suppressing or stabilizing such variations have been tested. Recently, a clinically significant reduction in the severity of the mental symptoms of PMDD was observed upon treatment with a selective progesterone receptor modulator (SPRM), as demonstrated when comparing ulipristal acetate with placebo in a randomised controlled trial. Stable and low progesterone levels, with maintained low-medium oestradiol levels, define the endocrine profile of this treatment. Importantly, the efficacy of SPRM treatment was accompanied by negligible side effects. These promising results represent a headway to understanding the mechanisms behind PMDD symptomatology and opening up new solutions in the management of PMDD. They also call for studies on the long-term efficacy, safety, and viability of SPRMs in female individuals during their fertile age to further support the development of targeted management of female's mental ill-health in relation to the menstrual cycle. The present overview thus seeks to inform about current and new pharmacological approaches to the management of premenstrual dysphoric disorder. (© 2023. The Author(s).)

Sung Calvin, T., et al. (2020). "Oral Metformin for Treating Dermatological Diseases: A Systematic Review." Journal of drugs in dermatology : JDD 19(8): 713-720.
	Introduction:Metformin is an antihyperglycemic medication most commonly used to treat Type II Diabetes Mellitus with promising off-label application for the treatment of hidradenitis suppurativa, psoriasis, acne, acanthosis nigricans, and hirsutism. Objective: To comprehensively assess evidence regarding the use of metformin for treating primary cutaneous disorders. Materials and Methods: A systematic literature search was conducted through PubMed, Cochrane, Web of Science, and CINAHL to identify the role of metformin in primary skin disease. Results: Sixty-four studies met inclusion criteria. Metformin demonstrates promising clinical response and favorable safety profile for treatment of HS, with most patients experiencing a decrease in frequency or severity of HS flares, and some experiencing full resolution of HS lesions. Patients with psoriasis treated with metformin experienced quantifiable clinical responses. Application of metformin on polycystic ovarian disease (PCOS) related acne, acanthosis nigricans, and hirsutism yielded mixed clinical results. No serious adverse effects were reported. Conclusion: Metformin is safe and efficacious and may be considered as an adjunctive therapy for the treatment of psoriasis and hidradenitis suppurativa in addition to first line therapies as well as PCOS related acne, acanthosis nigricans, and hirsutism. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4874.

Sung Vivian, W., et al. (2023). "Nonoperative Management of Pelvic Organ Prolapse." Obstetrics and Gynecology 141(4): 724-736.
	Pelvic organ prolapse (POP) is defined as the descent of one or more of the anterior, posterior, or apical vagina. It is a common condition, with up to 50% of women having prolapse on examination in their lifetimes. This article provides an overview of the evaluation and discussion of nonoperative management of POP for the obstetrician-gynecologist (ob-gyn), with consideration of recommendations from the American College of Obstetricians and Gynecologists, the American Urogynecologic Society, and the International Urogynecological Association. The initial evaluation of POP requires a history documenting whether the patient is experiencing symptoms and what they are, and discovery of which symptoms they believe are attributable to prolapse. Examination determines the vaginal compartment(s) and to what degree prolapse exists. In general, only patients who have symptomatic prolapse or medical indication should be offered treatment. Although surgical options exist, all patients who are symptomatic and desire treatment should be offered nonsurgical treatment first, including pelvic floor physical therapy or a pessary trial. Appropriateness, expectations, complications, and counseling points are reviewed. Educational opportunities between the patient and the ob-gyn include disentangling common beliefs that the bladder is dropping or that concomitant urinary or bowel symptoms are necessarily caused by prolapse. Improving patient education can lead to a better understanding of their condition and better alignment of treatment goals and expectations.; Competing Interests: Financial Disclosure Peter Jeppson reports receiving payment from Ethicon. Annetta Madsen did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Sunita, S., et al. (2021). "Exercise Therapy and Electrotherapy as an Intervention for Primary Dysmenorrhea. A systematic Review and Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	
Sunkara, S. and X. Guan (2022). "Robotic vaginal natural orifice transluminal endoscopic myomectomy." Fertility and Sterility 118(2): 414-416.
	Objective: To describe a novel, minimally invasive technique for performing myomectomy, a fertility-sparing procedure. Design(s): This technique was developed based on similar techniques for other surgeries that showed a benefit. Liu et al. (1) described vaginal natural orifice transluminal endoscopic surgery (vNOTES) for myomectomy, in which a 6-cm myoma was resected transvaginally. An anterior colpotomy was made, and single-site surgical skills were used to perform the entire myomectomy without an abdominal incision and with minimal blood loss (1). Another study showed that this technique was also feasible in 8 patients with type 3-7 myomas, and the patients were discharged within a day (2). Robotic vNOTES surgery has been performed for various gynecologic procedures, including hysterectomy, sacrocolpopexy, and the resection of endometriosis (3-6). One study showed that robotic vNOTES was a viable alternative to traditional vNOTES for hysterectomy, with no differences in operative time, the length of hospital stay, postoperative pain levels, or conversions (3). This study in fact proposed that robotic vNOTES was beneficial because of the opportunity to use wristed instruments to increase an otherwise limited range of motion. Another study showed that if surgeons already have significant experience with laparoscopic single-site and abdominal robotic surgeries, only 10 cases of robotic vNOTES and 10-20 port placements with robotic docking are needed to become proficient in robotic vNOTES (7). Another study showed that robotic vNOTES was a safe and feasible approach for the treatment of endometriosis with hysterectomy and the resection of endometriosis, which may be technically challenging because of distorted anatomy or scar tissue due to endometriosis (4). This video demonstrates a robotic vNOTES for myomectomy, a novel, minimally invasive technique for performing myomectomy. Vaginal surgery is the preferred route for hysterectomy compared with other techniques, and this parallel can also be made for other gynecologic procedures, including myomectomy (8). The vaginal approach is preferred for hysterectomy because it is associated with shorter hospital stays and operative time as well as faster recovery. Given these factors, the vaginal approach is preferred over the more traditional umbilical or abdominal laparoscopy. However, visualization and fine movement can be difficult in vaginal surgery, given the lack of space. Robotic techniques in place of traditional or vaginal laparoscopy do not require the surgeon to have a large amount of space to make fine movements because the camera and small robotic instruments are docked close to the tissue. This allows for precision while suturing and performing more layers in the myometrium after myomectomy. This is more difficult to achieve with traditional umbilical laparoscopy and may potentially reduce the risk of uterine rupture in future pregnancies. Given the advantages of the robotic and vaginal approaches, the robotic vNOTES route was pursued for this procedure because it combines the benefits of robotic and vaginal surgeries and can be considered as a feasible alternative to open, vaginal, or laparoscopic techniques. Setting(s): Academic-center hospital. Patient(s): A 28-year-old presented with heavy periods and pelvic pain. Imaging showed a large, 8-cm posterior fibroid, and the patient strongly desired a fertility-sparing approach. Intervention(s): Robotic vNOTES for myomectomy for the 8-cm posterior uterine fibroid. Main Outcome Measure(s): Feasibility and safety of using this technique for myomectomy. Result(s): Robotic vNOTES is a feasible option for performing minimally invasive myomectomy. In this technique, a posterior horizontal colpotomy was made and a gel port was placed through the incision. The DaVinci Robot was docked, and myomectomy was performed using single-incision surgical techniques. The uterine serosa was closed with the V-Loc suture, and an interceed adhesion barrier was placed over the incision. The surgeon should take care to notice that the e tire surgery is essentially performed "upside down" compared with the traditional abdominal laparoscopic approach. With this change in perspective, the surgeon should have a very good understanding of the vaginal anatomy and the expected location of the uterine artery, ureter, and rectum to avoid any damage to surrounding structures (the uterus) or increased blood loss. The fibroid was morcellated out of the vagina using The Extracorporeal C-Incision Tissue Extraction technique, and the posterior colpotomy was closed (9). The patient was discharged for home on the same day, with minimal blood loss. A prelabor cesarean section was recommended for all future pregnancies to reduce the risk of uterine rupture. The rate of uterine rupture after myomectomy is approximately 0.6% (10). However, the rate of uterine rupture after classical cesarean section is approximately 1%-12% (11). Given that the incision made was similar to the classical incision, except on the posterior uterus, prelabor cesarean section was recommended, although the uterine cavity was not entered. Conclusion(s): In this video, we demonstrate a myomectomy performed using the robotic vNOTES technique. The traditional vNOTES technique for myomectomy has been previously described (1); however, this technique can be very burdensome for suturing and does not allow for precision, and performing multiple layers is challenging. However, the robotic vNOTES approach solves this issue and can allow the surgeon to perform very precise suturing. While choosing the ideal patient for this procedure, the preoperative considerations include the desire for future fertility, the size and location of the fibroid, ideally 1 large posterior fibroid, and adequate space for vaginal port placement. This technique combines the advantages of both vaginal and robotic surgeries while maintaining low blood loss, and patients may be discharged for home on the same day.Copyright © 2022 American Society for Reproductive Medicine

Suradom, C., et al. (2021). "Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation for prevention and treatment of perinatal depression: a systematic review and meta-analysis of randomized-controlled trials." Nordic Journal of Psychiatry 75(4): 239-246.
	Background: Available interventions for preventing and treating perinatal depression remain unsatisfactory. Aim(s): We examined the prophylactic and therapeutic effects, as well as adverse effects, of n-3 PUFA supplementation in reducing depressive symptoms during perinatal periods. Method(s): We included randomized, placebo-controlled trials that reported the changes of depression severity after the perinatal participants received n-3 PUFA supplementation. After the comprehensive searches in October 2019, we selected the trials, extracted the data, and assessed the quality of included trials. We compared the standardized mean differences (SMD) of depression score changes between groups using a random-effect model. Result(s): We included 11 trials in the meta-analysis and one more trial for qualitative analysis (N = 3,181). The pooled standardized mean of decreased depression scores revealed no statistically significant difference between the n-3 PUFA and the placebo groups (N = 920, SMDs = -0.05, 95% CI -0.20 to 0.10, I2 = 21%). The pooled SMDs showed no statistically significant efficacy of n-3 PUFA supplementation for prevention (N = 779, SMDs = -0.03, 95% CI -0.20 to 0.13, I2 = 24%) and treatment (N = 141, SMDs = -0.14, 95% CI -0.55 to 0.27, I2 = 31%) of perinatal depression. The efficacy of n-3 PUFA supplementation was not associated with the daily doses of DHA, EPA, or DHA plus EPA. No trial reported any serious adverse effect of n-3 PUFA supplements. Conclusion(s): Although n-3 PUFA supplementation may improve maternal and infant outcomes, our meta-analysis found insufficient evidence to determine its benefit for perinatal depression.Copyright © 2020 The Nordic Psychiatric Association.

Surapaneni, S., et al. (2021). "Recurrent Bacterial Vaginosis: An Unmet Therapeutic Challenge. Experience With a Combination Pharmacotherapy Long-Term Suppressive Regimen." Sexually Transmitted Diseases 48(10): 761-765.
	BACKGROUND: Recurrence of bacterial vaginosis (RBV) is a major challenge to effective therapy. Women experiencing intractable and frequent recurrences are ill-served by available treatment options, such as both antimicrobial and use of probiotics. METHODS: One hundred five women with RBV failing all recommended regimens seen in the clinic were prescribed combination oral nitroimidazole 500 mg twice a day for 7 days and simultaneous boric acid 600 mg daily per vagina therapy for 30 days; thereafter, they were prescribed twice-weekly vaginal metronidazole gel for 5 months in an attempt to prevent recurrence and followed by a 6-month observation period. Results reflect standard of clinic care in this uncontrolled retrospective cohort analysis. RESULTS: An initial regimen of nitroimidazole and simultaneous but prolonged vaginal boric acid achieved a satisfactory response (BV cure ≤2 Amsel criteria) in 92 of 93 available patients. Thereafter, a maintenance metronidazole gel prevented symptomatic BV recurrence in 69.6% of compliant patients at 6-month follow-up. Long-term cure at a 12-month follow-up was demonstrated in almost 69% of women reaching the 6-month observation phase. Vaginal candidiasis frequently complicated prolonged antibiotic prophylaxis requiring frequent antifungal rescue or prophylaxis. Frequent loss to follow-up in this long-term study influenced efficacy evaluation. CONCLUSIONS: In the absence of new antimicrobials or proven probiotic regimens, women with RBV may benefit from a prolonged drug-intensive antimicrobial regimen incorporating antibiofilm activity until newer measures are available. Additional randomized, control studies are needed.

Suriati, M., et al. (2021). "Role of natural products in female sexual dysfunction: a systematic review and meta-analysis."
	
Surrey Eric, S. (2022). "GnRH agonists in the treatment of symptomatic endometriosis: a review." F&S reports 4(2 Suppl): 40-45.
	The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic endometriosis. Pituitary GnRH receptor down-regulation leads to a hypogonadotropic and secondary hypoestrogenic state resulting in lesion regression and symptom improvement. There may be an additional effect of these agents on the inflammatory processes associated with endometriosis as well. This is a review of critical milestones in the clinical application of these agents. Most initial trials of various GnRHa employed danazol as a control and demonstrated general equivalence in reducing symptoms and extent of lesions but without hyperandrogenic side effects and adverse metabolic changes induced by the latter. Short-acting GnRHa is administered intranasally or subcutaneously. Longer-acting preparations are administered intramuscularly or as subcutaneous implants. GnRHa also decrease symptom recurrence rates after surgical management. The hypoestrogenic side effects, including bone mineral density loss and vasomotor symptoms, have limited the duration of use of these agents alone to six months. The use of an appropriate add-back allows for the mitigation of side effects while maintaining efficacy and allowing extension of use for up to 12 months. There is a limited amount of data regarding the use of GnRHa in adolescents out of concern for the effect on developing bone. These agents should be used with caution in this group. The lack of dose flexibility, need for parental administration, and side effect profiles represent drawbacks to GnRHa use. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side effects represents an exciting alternative. (© 2022 The Author.)

Sustarsic, A., et al. (2023). "The influence of lifestyle interventions and overweight on infertility: a systematic review, meta-analysis, and meta-regression of randomized controlled trials." Frontiers in Medicine 10: 1264947.
	This study aimed to investigate the effect of lifestyle intervention (LSI) on diagnosed infertility in overweight and obese women. A systematic review and meta-analysis were conducted. A literature search was performed on the following databases from September 2022 to December 2022: PubMed, Web of Science, and SPORTDiscus. The inclusion criteria were the following: women between 18 and 45 years of age, BMI over 25.0 kg/m2, diagnosed with infertility, a weight loss intervention, and control group part of RCTs. In total, 15 studies were identified and included. The meta-analysis shows a beneficial effect of LSI on reducing weight, waist circumference, and BMI and increasing infertility. A significantly beneficial effect of lifestyle intervention on weight reduction was observed for participants who initially had a higher BMI, while a non-significant effect was observed for individuals with a BMI above 35 kg/m2. The meta-analysis showed a beneficial effect of lifestyle intervention on ovulation incidence and sex hormone-binding globulin. The lifestyle intervention group had 11.23 times more ovulatory incidence than the control group, which in turn increased the ability to conceive. As robust evidence for the effect of lifestyle interventions on infertility in obese and overweight women was found, it is advised to integrate similar interventions into future infertility treatment processes.

Sutanto, S. A., et al. (2022). "A Systematic Review on Isolated Coil Embolisation for Pelvic Venous Reflux." Journal of vascular surgery. Venous and lymphatic disorders 10(1): 224-232.e229.
	OBJECTIVE: Pelvic venous reflux (PVR) can present with symptoms such as chronic pelvic pain (CPP), dysmenorrhoea, and dyspareunia, resulting in reduced quality of life amongst those affected. Percutaneous coil embolisation (CE) is a common intervention for PVR, however the efficacy and safety of its use in isolation has yet to be reviewed. METHODS: The MEDLINE and EMBASE databases were systematically searched from 1990 to 20th July 2020 for studies reporting on adult patients undergoing isolated CE for PVR. Articles not in the English language, case reports, studies reporting on paediatric patients, and studies not performing isolated CE were excluded. Search, review, and data extraction were performed by two independent reviewers (SS and MT). Changes in pain pre- and post-CE was evaluated through a pooled analysis of visual analogue scale (VAS) scores in seven studies. RESULTS: A total of 970 patients (range 3-218, 100% female) undergoing isolated ovarian vein or mixed veins embolisation from 20 studies were included. Pooled analysis revealed mean improvements of 5.47 points (95% CI, 4.77-6.16) on the VAS. Common symptoms such as urinary urgency and dyspareunia reported significant improvements of 78-100% and 60-89.5% respectively. Complications were rare, with coil migration (n=19) being the most common. Recurrence rates differed based on the varying symptoms and studies, with recurrence in pain 1-2 years post-CE ranging from 5.9-25%. Two randomised controlled trials revealed improved clinical outcomes with CE as compared to vascular plugs and hysterectomy. CONCLUSIONS: The current data suggests that isolated CE is technically effective and can result in clinical improvement amongst patients with PVR. However, further trials are required to ascertain its long-term effects.

Sutanto Sharon, A., et al. (2022). "A systematic review on isolated coil embolization for pelvic venous reflux." Journal of vascular surgery. Venous and lymphatic disorders 10(1): 224.
	Objective: Pelvic venous reflux (PVR) can present with symptoms such as chronic pelvic pain, dysmenorrhea, and dyspareunia, resulting in a decreased quality of life among those affected. Percutaneous coil embolization (CE) is a common intervention for PVR; however, the efficacy and safety of its use in isolation has yet to be reviewed.; Methods: The MEDLINE and EMBASE databases were systematically searched from 1990 to July 20, 2020, for studies reporting on adult patients undergoing isolated CE for PVR. Articles not in English, case reports, studies reporting on pediatric patients, and studies not performing isolated CE were excluded. Search, review, and data extraction were performed by two independent reviewers (S.S. and M.T.). Changes in pain before and after CE was evaluated through a pooled analysis of visual analogue scale scores in seven studies.; Results: A total of 970 patients (range, 3-218, 100% female) undergoing isolated ovarian vein or mixed veins embolization from 20 studies were included. Pooled analysis revealed mean improvements of 5.47 points (95% CI, 4.77-6.16) on the visual analogue scale. Common symptoms such as urinary urgency and dyspareunia reported significant improvements of 78-100% and 60-89.5% respectively. Complications were rare, with coil migration (n = 19) being the most common. Recurrence rates differed based on the varying symptoms and studies, with recurrence in pain 1-2 years after CE ranging from 5.9-25%. Two randomized controlled trials revealed improved clinical outcomes with CE as compared with vascular plugs and hysterectomy.; Conclusions: The current data suggests that isolated CE is technically effective and can result in clinical improvement among patients with PVR. However, further trials are required to ascertain its long-term effects. (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Suvaal, I., et al. (2021). "A sexual rehabilitation intervention for women with gynaecological cancer receiving radiotherapy (SPARC study): design of a multicentre randomized controlled trial." BMC Cancer 21(1): 1295.
	Background: Sexual problems are frequently reported after treatment with radiotherapy (RT) for gynaecological cancer (GC), in particular after combined external beam radiotherapy and brachytherapy (EBRT+BT). Studies demonstrate that psychosexual support should include cognitive behavioural interventions and involvement of the patient's partner, if available. Therefore, we developed a nurse-led sexual rehabilitation intervention, including these key components. The intervention was previously pilot-tested and results demonstrated that this intervention improves women's sexual functioning and increases dilator compliance. The objective of the current study is to investigate the (cost-)effectiveness of the intervention compared to optimal care as usual (CAU). We expect that women who receive the intervention will report a statistically significant greater improvement in sexual functioning and - for women who receive EBRT+BT - higher compliance with dilator use, from baseline to 12 months post-RT than women who receive optimal care as usual (CAU). Methods/design: The intervention is evaluated in the SPARC (Sexual rehabilitation Programme After Radiotherapy for gynaecological Cancer) study, a multicentre, randomized controlled trial (RCT). The primary endpoint is sexual functioning. Secondary outcomes include body image, fear of sexual activity, sexual-, treatment-related- and psychological distress, health-related quality of life and relationship satisfaction. A cost-effectiveness analysis (CEA) will be conducted in which the costs of the intervention will be related to shifts in other health care costs and the impact on patient outcome. The study sample will consist of 220 women with GC treated with RT in specialized GC treatment centres (N = 10). Participants are randomized to either the intervention- or CAU control group (1:1), and within each centre stratified by type of radiotherapy (EBRT+BT vs. EBRT only) and having a partner (yes/no). All women complete questionnaires at baseline (T1) and at 1, 3, 6, and 12 months post-RT (T2, T3, T4 and T5, respectively). Discussion(s): There is a need to improve sexual functioning after RT for GC. This RCT will provide evidence about the (cost-)effectiveness of a nurse-led sexual rehabilitation intervention. If proven effective, the intervention will be a much needed addition to care offered to GC survivors and will result in improved quality of life. Trial registration: ClinicalTrials.gov, NCT03611517. Registered 2 August 2018.Copyright © 2021, The Author(s).

Suvannasarn, R., et al. (2022). "Health-related quality of life for early-stage cervical cancer survivors after primary radical surgery followed by radiotherapy versus radical surgery alone." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(5): 1217-1224.
	This study compared the quality of life (QoL) of 265 stage IA2-IIA cervical cancer patients treated with radical surgery alone (group 1: 137 patients) versus those who underwent primary radical surgery followed by radiotherapy (group 2: 128 patients) and identified clinical characteristics that predict the poor quality of life. All participants completed quality of life questionnaires: EORTC QLQ-C30 and CMU cervical cancer QoL. For the EORTC QLQ-C30, the study groups were comparable regarding global health status/QoL scale and summary scores. Group 1 participants had better scores on the physical functioning domain and some symptom scales/items. For the CMU Cervical Cancer QoL, group 1 participants had better scores on gastrointestinal, lymphatic, and sexual/hormonal domains. In multivariable analysis, adjuvant radiation was consistently associated with poor quality of life in most domains. In general, early-stage cervical cancer survivors had a satisfactory quality of life. The clinical significance of the quality of life score differences between the study groups remains debateable.Impact statement What is already known on this subject? For women with early cervical cancer, surgery is the main treatment providing not only a good chance for a cure by total removal of the cancer but also an opportunity to preserve the hormone-producing function of the ovary as well as the flexibility of the vagina. However, radiation treatment may be indicated after surgery in some patients depending on the findings from surgery. Because of the concern about increased complications and decreased long-term quality of life following the combined treatments, some may elect to avoid surgery and receive radiation alone in the first place. In this study, we compared the quality of life of women who had surgery alone to those who had surgery followed by radiation. This information is currently lacking in the medical literature. What do the results of this study add? We found that, in general, women with early cervical cancer had a satisfactory quality of life. For a patient who is surgically fit and chooses to receive primary surgery, if radiation is subsequently required, she could still expect the acceptable long-term quality of life-although slightly less satisfactory than receiving surgery alone but not inferior to those who receive primary radiation treatment. What are the implications of these findings for clinical practice and/or further research? These findings will be useful for pre-treatment counselling and posttreatment supportive care. The information regarding disease-related and treatment-induced morbidity should be thoroughly discussed with the patients before and after treatment. Also, the use of questionnaires examining general well-being together with a cancer-specific quality of life is recommended for the systematic evaluation of cancer survivors.

Suzhen, J. and H. Jincheng (2022). "Efficacy and safety of photodynamic therapy in women with HSIL, LSIL and human papilloma virus infection&#xff1a;a systematic review and meta-analysis of randomized clinical trials."
	
Suzhou Suncadia Biopharmaceuticals, C. and Ltd (2024). A Study of SHR-A1921 With or Without Carboplatin in Subjects With Ovarian Cancer.
	No Results Available Drug: SHR-1921|Drug: carboplatin|Drug: platinum-based doublet chemotherapy Objective Response Rate Assessed by Investigator According to RECIST v1.1|Duration of Response (DoR) Assessed by Investigator as per RECIST 1.1|Disease Control Rate (DCR) Assessed by Investigator as per RECIST 1.1|Progression-Free Survival (PFS) Assessed by Investigator as per RECIST 1.1|Overall Survival (OS)|CA-125 Response assessed by the Gynecologic Cancer Intergroup (GCIG) criteria Female Phase 2|Phase 3 520 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment SHR-A1921-301 June 15, 2026

Suzuki, T., et al. (2021). "Effect of oxybutynin patch versus mirabegron on nocturia-related quality of life in female overactive bladder patients: a multicenter randomized trial." International Journal of Urology 28(9): 944‐949.
	Objectives: To investigate the effect of oxybutynin patch versus β3‐adrenoceptor agonist mirabegron on nocturia‐related quality of life in female overactive bladder patients. Methods: In the present study, female overactive bladder patients were enrolled. The patients were randomly allocated into two groups: the oxybutynin patch group and the mirabegron group. Each of the drugs was given for 8 weeks. The changes in the total Nocturia Quality of Life Questionnaire score were evaluated. Parameters on a frequency volume chart were also evaluated. Results: In total, 100 patients (51 oxybutynin patch, 49 mirabegron) were treated with oxybutynin patch or mirabegron. The changes in the Nocturia Quality of Life Questionnaire score 4 weeks after administration were 3.8 ± 18.6 and 8.7 ± 13.1 with the oxybutynin patch group and the mirabegron group, respectively, which were significantly higher than those at the baseline. Furthermore, the changes in the Nocturia Quality of Life Questionnaire score 8 weeks after administration were 4.3 ± 16.5 and 7.7 ± 12.3, respectively. A statistical difference was seen only in the mirabegron group. Regarding the Nocturia Quality of Life Questionnaire subscores, oxybutynin patch and mirabegron significantly improved the Nocturia Quality of Life Questionnaire bother/concern subscore 4 and 8 weeks after administration, whereas the Nocturia Quality of Life Questionnaire sleep/energy subscore was not significantly improved in each period. Eight weeks after administration, 24‐h frequency, 24‐h urinary urgency and mean voided urine volume were improved in both groups statistically. Conclusions: The oxybutynin patch improves quality of life, focusing mainly on nocturia by improving the bother/concern subscores of the Nocturia Quality of Life Questionnaire in the short term.

Suzuki, Y., et al. (2024). "Estrogen replacement therapy and non-hormonal medication use among patients with uterine cancer." Gynecologic Oncology 180: 14-23.
	Objective: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. Method(s): The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. Result(s): A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). Conclusion(s): The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.Copyright © 2023 Elsevier Inc.

Suzuki, Y., et al. (2023). "Increasing use and outcomes of oral and intrauterine progestin therapy for premenopausal women with endometrial intraepithelial neoplasia (2198)." Gynecologic Oncology 176(Supplement 1): S255-S256.
	Objectives: While hysterectomy remains the standard of care for endometrial intraepithelial neoplasia (EIN), conservative therapy may be utilized in young women who wish to preserve fertility. Little is known about the patterns of use and outcomes of fertility-preserving treatments for young patients with EIN. We examined trends in the use and outcomes of progestational therapy for premenopausal patients with EIN. Method(s): The IBM Watson Health MarketScan Database was used to identify patients aged 18-50 years with EIN from 2008 to 2020. Primary treatment was classified as hysterectomy or medical therapy with progestins. Within the progestin group, we classified treatment as progestin-releasing intrauterine device (P-IUD) and other progestin (oral progestin or injectable progestin). The trends in the use of progestins and the pattern of progestin use were examined using the Cochran-Armitage trend test. The duration of therapy, use and time to hysterectomy from the start of progestin, rate of cancer, and major progestin-associated complications were reported descriptively. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. Result(s): A total of 3947 patients were identified. Hysterectomy was performed in 2149 (54.4%), while progestins were utilized in 1798 (45.6%). The use of medical therapy increased from 44.2% in 2008 to 63.4% in 2020 (P = 0.002). Progestins were used in 88.3% of patients aged 18-30 years, in 62.7% of those aged 31-40 years, and in 33.6% of patients aged 41-50 years (P < 0.001). In a multivariable model, younger age and a history of PCOS were associated with progestin use while patients with a history of breast cancer were less likely to use progestins (P < 0.05 for all). Among the progestin users, 1487 (82.7%) were treated with oral agents, and 311 (17.3%) were treated with a progesterone intrauterine device (P-IUD). Among those who received progestins, the use of P-IUD increased from 9.2% in 2008 to 37.8% in 2020 (P < 0.001). The median duration of therapy in the oral P group was 60 days (IQR: 30-120 days). Overall, 392 (21.8%) patients treated with progestin underwent a hysterectomy 30 days or more after the start of progestin therapy. The median time to hysterectomy was 63 days (IQR: 46-86 days) and was similar for those treated with oral progestins and P-IUD. Sixty (3.3%) patients treated with primary progestin progressed to endometrial cancer (median time-to-cancer 83 days, IQR: 52-128 days). Endometrial cancer was diagnosed in 3.8% of those treated with oral progestins compared to 1.3% of those treated with P-IUD (P = 0.03). Venous thromboembolic complications occurred in 0.6% of those treated with progestins; the VTE rate was similar for oral progestins and P-IUD. Conclusion(s): The rate of conservative treatment with progestins in premenopausal women with EIN has increased over time. Among progestin users, progesterone-releasing IUD use is increasing. Progesterone IUDs are associated with a lower risk of cancer and similar toxicity to oral progestin therapy. [Formula presented]Copyright © 2023

Suzuki, Y., et al. (2023). "Systemic Progestins and Progestin-Releasing Intrauterine Device Therapy for Premenopausal Patients With Endometrial Intraepithelial Neoplasia." Obstetrics and Gynecology 141(5): 979-987.
	Objective: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia.; Methods: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed.; Results: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD.; Conclusion: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy.; Competing Interests: Financial Disclosure Yukio Suzuki reports receiving payment from The Japan Society for Menopause and Women's Health (JMWH Bayer Grant 2022) and from Honjo (JMSA Scholarship 2022). They received a Honjo-JMSA Scholarship and a JMWH Bayer Grant from the Japan Society for Menopause and Women's Health. Jason D. Wright has received royalties from UpToDate and research support from Merck. The other authors did not report any potential conflicts of interest. (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Suzuki, Y., et al. (2024). "Levonorgestrel-releasing intrauterine device therapy versus oral progestin treatment for Reproductive-Aged patients with endometrial intraepithelial neoplasia: a systematic review and Meta-Analysis." Journal of the National Cancer Institute.
	BACKGROUND: We conducted a systematic review and meta-analysis to examine outcomes of patients with endometrial intraepithelial neoplasia (EIN) treated with oral progestins or levonorgestrel-releasing intrauterine device (LNG-IUD). METHODS: We conducted a systematic review across five databases to examine outcomes of progestational treatment (oral progestins or LNG-IUD) for patients with EIN. The primary outcome was the best complete response (CR) rate within twelve months of primary progestational treatment. Sensitivity analyses were performed by removing studies with extreme effect sizes. Secondary outcomes included the pooled pregnancy rate. RESULTS: We identified 21 eligible studies, including 824 premenopausal patients with EIN, for our meta-analysis. Among these, 459 patients received oral progestin, while 365 patients received LNG-IUD as a primary progestational treatment. The pooled best CR proportion within 12 months was 82% (95% CI, 69-91) following oral progestin treatment, and 95% (95% CI, 81-99) following LNG-IUD treatment. After removing outlier studies, the pooled proportion was 86% (95% CI, 75-92) for the oral progestin group, and 96% (95% CI, 91-99) for the LNG-IUD group, with reduced heterogeneity. The pooled pregnancy rate was 50% (95% CI, 35-65) after oral progestin and 35% (95% CI, 23-49) after LNG-IUD treatment. CONCLUSIONS: This meta-analysis provides data on the effectiveness of oral progestins and LNG-IUD treatment within 12 months of treatment among premenopausal patients with EIN. Although based on small numbers, the rate of pregnancy after treatment is modest. These data may be beneficial for selecting progestational therapies that allow fertility preservation for patients with EIN.

Suzuki, Y., et al. (2023). "Prescription of hormone replacement therapy among cervical cancer patients with treatment-induced premature menopause." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(1): 26-34.
	Objective: To examine the utilization of hormone replacement therapy (HRT) among newly diagnosed cervical cancer patients who experienced premature menopause due to primary treatment.; Methods: The MarketScan Databases were used to identify newly diagnosed cervical cancer patients <50 years of age with premature menopause after hysterectomy with bilateral salpingo-oophorectomy (primary surgery) or primary external beam pelvic radiation (primary radiotherapy). We examined the cumulative utilization of HRT until 24 months after the loss of ovarian function. Fine-Gray subdistribution hazard models were developed to examine the factors associated with cumulative HRT use. The duration of HRT use was analyzed by Kaplan-Meier curves.; Results: A total of 1826 patients, including 352 (19.3%) who underwent primary surgery and 1474 (80.7%) who received primary radiotherapy, were identified. Overall, 39.0% of patients received HRT within 24 months of primary treatment. HRT was used in 49.4% of those who underwent primary surgery and in 36.6% of those who received primary radiotherapy (p<0.0001). The median duration of HRT use was 60 days among the entire cohort and was significantly shorter for the primary radiotherapy group than the primary surgery group (35 vs 90 days, p<0.0001). Primary radiotherapy, older age, residency in the Northeastern USA, and Black race were associated with a lower likelihood of HRT use.; Conclusions: HRT was prescribed to less than half of patients with newly diagnosed cervical cancer under the age of 50 who experienced premature menopause due to primary treatment. Among those who used HRT the duration of use was short.; Competing Interests: Competing interests: JDW has received royalties from UpToDate and received research funding from Merck. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Svane Inge, M. and H. Hospital (2021). T-cell Therapy in Combination With Nivolumab, Relatlimab and Ipilimumab for Patients With Metastatic Ovarian Cancer.
	No Results Available Drug: Ipilimumab|Drug: Cyclophosphamid|Drug: Fludarabine Phosphate|Biological: Tumor Infiltrating Lymphocytes infusion|Drug: Nivolumab|Drug: Relatlimab Number of patients excluded due to treatment related safety issues|Fraction of patients experiencing grade III or worse adverse events|Number of patients excluded due to feasibility issues|Best overall response (BOR) All Phase 1|Phase 2 18 Other Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment GY2028 December 2023

Svihra, J., et al. (2021). "Impact of innovative pelvic floor muscle training on quality-adjusted life years (QALYs) in women with stress urinary incontinence treated by duloxetine." European Journal of Obstetrics, Gynecology, and Reproductive Biology 264: 25-30.
	OBJECTIVES: The aim of this study was to measure the impact of innovative pelvic floor muscle training (iPFMT) on Quality-Adjusted Life Years (QALYs) in women with stress urinary incontinence (SUI) treated by duloxetine. STUDY DESIGN: This analysis is part of the DULOXING study conducted between February 2019 and 2020. The control group received oral duloxetine treatment (40 mg BID), and the experimental group received oral duloxetine treatment (40 mg BID) and iPFMT with lumbopelvic stabilization. SUI was analysed at baseline and in the final period according to the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). The QALYs gained were calculated by multiplying life expectancy (LE) by a weighting factor (QALYs = LE * WF). RESULTS: The study included 158 women, of whom 129 were fully analysed (81.6%). The mean life expectancy was 26.3 ± 11.8 years for the control group and 29.0 ± 11.7 years for the experimental group. The mean baseline ICIQ-UI SF scores were 15.2 ± 1.7 vs 15.1 ± 1.5, and the final ICIQ-UI SF scores were 9.8 ± 4.2 vs 8.3 ± 3.8, in the control vs the experimental group, respectively (p < 0.05). The mean baseline WF was 0.27 ± 0.08 vs 0.28 ± 0.07, and the final WF was 0.53 ± 0.20 vs 0.60 ± 0.18, in the control vs the experimental group, respectively (p < 0.05). Before treatment, the number of QALYs during life expectancy in the control vs the experimental group was 7.53 ± 4.24 vs 8.30 ± 4.01. The number of QALYs during life expectancy in control vs the experimental group increased following treatment: 15.03 ± 7.63 vs 17.90 ± 7.86 (p < 0.05). CONCLUSIONS: Combination treatment with duloxetine and iPFMT statistically significantly increased the number of QALYs and reduced the degree of urinary incontinence in women with stress urinary incontinence.

Swallow, C. H., et al. (2023). "Universal Urogynecologic Consultation and Screening for Fecal Incontinence in Pregnant Women with a History of Obstetric Anal Sphincter Injury: A Cost-Effectiveness Analysis." Urogynecology 29(3): 351-359.
	Importance: Obstetric anal sphincter injuries (OASIS) predispose for the development of fecal incontinence (FI), but management of subsequent pregnancy after OASIS is controversial. Objective(s): We aimed to determine if universal urogynecologic consultation (UUC) for pregnant women with prior OASIS is cost-effective. Study Design: We performed a cost-effectiveness analysis of pregnant women with a history of OASIS modeling UUC compared with no referral (usual care). We modeled the route of delivery, peripartum complications, and subsequent treatment options for FI. Probabilities and utilities were obtained from published literature. Costs using a third-party payer perspective were gathered from the Medicare physician fee schedule reimbursement data or published literature converted to 2019 U.S. dollars. Cost-effectiveness was determined using incremental cost-effectiveness ratios). Result(s): Our model demonstrated that UUC for pregnant patients with prior OASIS was cost-effective. Compared with usual care, the incremental cost-effectiveness ratio for this strategy was $19,858.32 per quality-Adjusted life-year, below the willingness to pay a threshold of $50,000/quality-Adjusted life-year. Universal urogynecologic consultation reduced the ultimate rate of FI from 25.33% to 22.67% and reduced patients living with untreated FI from 17.36% to 1.49%. Universal urogynecologic consultation increased the use of physical therapy by 14.14%, whereas rates of sacral neuromodulation and sphincteroplasty increased by only 2.48% and 0.58%, respectively. Universal urogynecologic consultation reduced the rate of vaginal delivery from 97.26% to 72.42%, which in turn led to a 1.15% increase in peripartum maternal complications. Conclusion(s): Universal urogynecologic consultation in women with a history of OASIS is a cost-effective strategy that decreases the overall incidence of FI, increases treatment utilization for FI, and only marginally increases the risk of maternal morbidity.Copyright © 2023 by the Author(s).

Swati, S., et al. (2023). "Is there any association between Endometrial compaction and the clinical outcomes following embryo transfer (fresh/frozen) in an ART ( assisted reproductive technology) cycle?".
	
Swift, B., et al. (2022). "Adverse postoperative outcomes associated with perioperative blood transfusion in gynecologic oncology surgery: a National Surgical Quality Improvement Program analysis (467)." Gynecologic Oncology 166(Supplement 1): S232.
	Objectives: To examine the incidence of perioperative blood transfusion and association with 30-day postoperative outcomes in gynecologic cancer surgery. Method(s): The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried to identify all gynecologic oncology cases from 2013 to 2019. Clinical and surgical characteristics and 30-day postoperative complications were retrieved. The primary outcome was 30-day composite morbidity, based on the occurrence of one or more of the 18 adverse events defined by NSQIP. The secondary outcomes were 30-day mortality, length of stay, and composite surgical site infection (SSI), defined as superficial, deep, or organ space SSI. Chi-square analysis and logistic regression models were performed to compare patients with and without perioperative blood transfusion. Result(s): There were 63,198 surgical gynecologic oncology cases with an overall transfusion incidence of 9.8%. The transfusion incidence was significantly higher at 22.6% with laparotomy compared to 2.2% with minimally invasive surgery (p<0.0001). In patients undergoing laparotomy, transfusion was significantly associated with the following preoperative factors: age, lower BMI, steroid use, bleeding disorders, dyspnea, weight loss, low albumin, low hematocrit, low platelet count, higher INR, and patients who required preoperative transfusion (p<0.0001). Transfusion was more common in patients with ovarian cancer compared to uterine or cervical cancer (p<0.0001). Intraoperative factors associated with transfusion were disseminated disease, ascites, longer operative time, and multivisceral resection (p<0.0001). On multivariable analysis, transfusion was predictive of composite morbidity (adjusted odds ratio (OR): 1.66, 95% CI: 1.48-1.85) and length of stay (LOS) in hospital > 5 days (adjusted OR: 9.14, 95% CI: 8.32-10.04). Other significant factors in the models predicting composite morbidity and LOS?> 5 days are shown in Figure 1. Transfusion was not significantly associated with composite SSI (OR: 1.03, 95% CI: 0.85-1.24) or mortality (OR: 1.15, 95% CI: 0.63-2.10). In a subgroup analysis of ovarian cancer patients with disseminated cancer (n=3,747), the incidence of perioperative blood transfusion was 38.1%. On multivariable analysis, transfusion was the only predictive factor for composite morbidity (adjusted OR: 1.68, 95% CI: 1.34-2.11) and LOS in hospital > 7 days (adjusted OR: 17.50, 95% CI: 13.85-22.12). The other parameters in the models were not significantly associated with composite morbidity or LOS?> 7 days. Conclusion(s): Perioperative blood transfusion occurs in 22.6% of open gynecologic oncology surgeries and 38.1% ovarian cancer debulking. They are associated with increased composite morbidity and prolonged hospital admission. Preoperative patient optimization and institutional practices should be reviewed to improve the use of blood bank resources and adherence to restrictive transfusion protocols.Copyright © 2022 Elsevier Inc.

Swift, B., et al. (2022). "The Cyprus women's health research (COHERE) initiative: estimating the prevalence, symptomatology, associated risk factors and economic burden of endometriosis in an Eastern Mediterranean population." Human Reproduction 37(Supplement 1): i37-i38.
	Study question: In this previous undescribed population of women, what is the prevalence of endometriosis and associated symptomatology, and how are women affected? Summary answer: Prevalence of endometriosis was 5.4% (95%CI; 4.9%-5.9%). Cases suffered from worse physical health, higher use of pain medication and decreased productivity at work. What is known already: There is a lack of population level data on prevalence and distribution of women's health conditions, such as endometriosis, from the Eastern Mediterranean region, despite their known negative effects on quality of life. In addition, there is a complete absence of any health statistics from Northern Cyprus, an emerging region in Europe. Most current endometriosis research comes from Western populations and is not generalisable to non-Western populations due to differences in culture, lifestyle, and care seeking patterns. Therefore, it is important to investigate endometriosis in a variety of settings. Study design, size, duration: The COHERE Initiative is a cross-sectional, population-based study that recruited 7,646 women between the ages 18-55 residing in Northern Cyprus between January 31st 2018, and January 31st 2020. Recruitment took place face-to-face (90%) and online (10%). Participants completed an expanded version of the WERF Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) questionnaire, consisting of previously validated measurement instruments, such as the Short-Form-36-version-2 questionnaire (SF-36v2) and the Work Productivity and Impairment Questionnaire: General Health (WPAI:GH). Participants/materials, setting, methods: Endometriosis cases were defined using a combination of self-reported and pelvic ultrasound data. Controls were women without endometriosis. Chi-square, Fisher's exact test, Student's t-test, linear regression, and multivariable logistic regression were used for data analysis. The significance level was set at p<0.05. Main results and the role of chance: Endometriosis prevalence was 5.4% (95%CI; 4.9%-5.9%;n=410). The mean age women with endometriosis reported to first experience related-symptoms was 25.9-years, despite average age of first menstrual-pain occurring at 16.2-years. Average age of first gynaecologist visit was 21.0-years and endometriosis diagnostic-delay was 1.5-years. Physical health-related-quality-of-life was lower in women with endometriosis compared to those without (48.4 vs 50.2, p=0.001). Cases had a higher mean percentage of activity impairment (25.8% vs 22.5%, p=0.03) and reduced effectiveness whilst working (23.4% vs 19.5%, p=0.006) than controls. Hormone-use was higher in women with endometriosis compared to controls for heavy-bleeding (5.9% vs 1.4%, p<0.001), irregular periods (14.4% vs 7.2%, p<0.001) and pelvic-pain (9.3% vs 1.7%, p<0.001), though overall hormone use was low at 24.1%. Iron and vitamin-D deficiency were the most reported co-morbidities, and these proportions were significantly different from women without endometriosis (38.8% vs 28.3%, 23.9% vs 17.0% respectively, p<0.001). Migraine headaches were more frequent in women with endometriosis than in those without (19.8% vs 13.2%, p<0.001). Women with endometriosis were more likely to have ever used drugs for pain relief (77.1% vs 60.5%, p<0.001). Further analysis will include estimation of economic burden of endometriosis and investigation into Mediterranean-specific factors including sun-exposure and dietary-habits. Limitations, reasons for caution: Given the cross-sectional nature of this study, causality cannot be inferred. The majority of endometriosis cases are self-reported which is not as reliable as hospital diagnosis/surgeries and laparoscopy is not available in Northern Cyprus. However, research has shown that women self-report endometriosis diagnoses with reasonable accuracy (>70%). Wider implications of the findings: This is the first study that has estimated prevalence of endometriosis in the region and provided insight into the current-status of healthcare. It has highlighted gaps in the public's g neral knowledge of common gynaecological conditions. The results form the basis for targeted follow-up-studies and promotes evidence-based reproductivemedicine in the Eastern-Mediterranean-region.

Swift, B. E., et al. (2022). "Lymphadenectomy for high-grade endometrial cancer: Does it impact lymph node recurrence?" European Journal of Surgical Oncology 48(5): 1181-1187.
	Introduction: The diagnostic role of lymph node (LN) assessment is established in endometrial cancer. Our study assesses whether surgical removal of metastatic LNs has oncologic benefit in high-grade endometrial cancer. Material(s) and Method(s): High-grade endometrial cancer cases (2000-2010) were collected from two tertiary cancer centres. In patients with at least one positive LN, recurrence free survival (RFS) was compared by the number of LNs removed. Factors predicting nodal recurrence (NR) were explored. Univariate statistical analyses by log rank test and multivariable cox proportional hazards model were performed using SAS version 9.4. Result(s): Of 570 patients identified, 334 patients underwent staging lymphadenectomy, 74 (22.2%) patients had at least one positive LN. The median RFS with at least one positive lymph node was 87.1 months (95% CI >= 14.3) when greater than 15 LNs were removed, compared to 16.9 months (95% CI, 13.6-35.6) and 17.3 months (95% CI, 8.5-39.8) when 5-15 and less than 5 LNs were removed, respectively (p = 0.02). In the cohort of 570 patients, there were 167 disease recurrences with location described on imaging, 98 (58.7%) had a NR and 69 (41.3%) recurred at other sites. Multivariable modeling identified that only positive LNs at surgical staging predicted NR (HR 3.8, 95% CI 1.4-10.2). Conclusion(s): In high-grade endometrial cancer, positive LNs predict NR, and RFS is longer with a more extensive LN dissection in women with positive LNs. Future prospective studies should evaluate the oncologic benefit of surgical removal of metastatic LNs in high-grade endometrial cancer.Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology

Swift Brenna, E., et al. (2022). "The effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, grade 1 and 2 endometrioid ovarian carcinoma." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(4): 525-531.
	Objectives: To assess the effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, low grade endometrioid ovarian cancer.; Methods: This retrospective study was conducted at two cancer centers from July 2001 to December 2019. Inclusion criteria were all stage I, grade 1 and 2 endometrioid ovarian cancer patients. Patients with mixed histology, concurrent endometrial cancer, neoadjuvant chemotherapy, and patients who did not undergo follow-up at our centers were excluded. Clinical, pathologic, recurrence, and follow-up data were collected. Cox proportional hazard model evaluated predictive factors. Recurrence-free survival and overall survival were calculated using the Kaplan-Meier method.; Results: There were 131 eligible stage I patients: 83 patients (63.4%) were stage IA, 5 (3.8%) were stage IB, and 43 (32.8%) were stage IC, with 80 patients (61.1%) having grade 1 and 51 (38.9%) patients having grade 2 disease. Complete lymphadenectomy was performed in 34 patients (26.0%), whereas 97 patients (74.0%) had either partial (n=22, 16.8%) or no (n=75, 57.2%) lymphadenectomy. Thirty patients (22.9%) received adjuvant chemotherapy. Median follow-up was 51.5 (95% CI 44.3 to 57.2) months. Five-year recurrence-free survival was 88.0% (95% CI 81.6% to 94.9%) and 5 year overall survival was 95.1% (95% CI 90.5% to 99.9%). In a multivariable analysis, only grade 2 histology had a significantly higher recurrence rate (HR 3.42, 95% CI 1.03 to 11.38; p=0.04). There was no difference in recurrence-free survival (p=0.57) and overall survival (p=0.30) in patients with complete lymphadenectomy. In stage IA/IB, grade 2 there was no benefit of adjuvant chemotherapy (p=0.19), and in stage IA/IB, low grade without complete surgical staging there was no benefit of adjuvant chemotherapy (p=0.16). Twelve patients (9.2%) had recurrence; 3 (25%) were salvageable at recurrence and are alive with no disease.; Conclusions: Patients with stage I, low grade endometrioid ovarian cancer have a favorable prognosis, and adjuvant chemotherapy and staging lymphadenectomy did not improve survival.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Swisher Elizabeth, M., et al. (2022). "Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study." Gynecologic Oncology 164(2): 245-253.
	Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.; Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks.; Results: Of 1140 patients randomized, 742 had BRCA wild type (BRCAwt) tumors (HRP, n = 373; HRD/BRCAwt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCAwt populations (HRD/BRCAwt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53-1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56-1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCAwt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control.; Conclusions: These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Swisher, E. M., et al. (2023). "Phase 1b/2a clinical trial of the oral BET inhibitor PLX2853 as monotherapy for ARID1A mutated gynecologic cancers and in combination with carboplatin for platinum resistant ovarian cance." Cancer Research 83(8 Supplement).
	The Bromodomain and Extra-Terminal (BET) Domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with ARID1A loss. PLX2853 is an orally active, small molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all 4 BET family members (BRD2, BRD3, BRD4, and BRDT). PLX2853 development is continuing at Opna Bio as OPN-2853. Clinical experience with PLX2853 monotherapy in subjects with heavily pretreated solid tumors and lymphoma showed signs of activity. The current study (NCT04493619) was designed as a multicenter, open-label trial with two parallel arms: (1) a phase 2a study of PLX2853 monotherapy in advanced gynecological malignancies with a known ARID1A mutation and (2) a phase Ib/2a combination study of PLX2853 plus carboplatin in platinum resistant OC. The primary objective of the Ib portion of the study was safety and tolerability, with the primary objective of both phase 2a portions being efficacy. In the monotherapy arm, up to 6 patients were treated at 80 mg PLX2853 daily in a safety lead-in, with progression to phase 2a using a Simon 2-stage design if dose limiting toxicities (DLTs) were observed in fewer than 33% subjects. In Stage 1, 6 additional subjects (N=12 total) were planned, with progression to stage 2 if two or more patients responded in stage 1. The combination arm included an escalation phase Ib. Three to six evaluable subjects were planned for each group, with dose escalation pending less than 33% DLT rate. The combination arm defined by the phase 1b portion of the study continued to a planned phase 2a Simon 2 stage design similar to that described for the monotherapy arm. 34 of 37 enrolled patients were evaluable with data from at least 1 post baseline response (14 monotherapy, 20 combination therapy). Of the 14 evaluable patients on the monotherapy arm, 1 (7.1%) achieved a partial response (PR) with progression-free survival of 278 days, 5 (35.7%) had stable disease (SD) and 8 (57.1%) had progressive disease (PD). Of the 20 evaluable OC patients on the PLX2843 + carboplatin combination, 1 (5.0%) had PR, 9 (45.0%) had SD, and 10 (50%) had PD. This study in a larger cohort of gynecologic cancer patients confirmed the safety profile of the agent and demonstrated the feasibility of combination with carboplatin. While these results did not meet the pre-specified response criteria, evidence of clinical activity nevertheless highlights the rationale for further exploration of BRD4 inhibitors in patients with ARID1A-mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway, frequently activated in these cancers.

Syed, S. A., et al. (2023). "Outcome of First Trimester Induced Abortions Using Misoprostol by Buccal and Vaginal Routes." Journal of South Asian Federation of Obstetrics and Gynaecology 15(4): 462-464.
	Aims of study: To study the outcome of buccal and vaginal administration of Misoprostol in first-trimester induced abortions. To study thinduction-abortion interval, duration of bleeding, failure rate, side effects, and patient satisfaction among both routes. Material(s) and Method(s): A prospective observational study was carried out on 110 women requesting for first-trimester abortion as per medical termination of pregnancy (MTP) Act. They were divided into two groups, i.e., vaginal and buccal. The vaginal group comprised 55 patients who were given oral Mifepristone, followed by vaginal Misoprostol (800 microg). In the buccal group, consisting of 55 patients, oral Mifepristone was administered, followed by buccal Misoprostol (800 microg). Results were compared between the groups in terms of induction-abortion interval, duration of bleeding, failure rate, side effects, safety, effectiveness, and patient satisfaction. Result(s): The rate of complete abortion was 92.7% in the vaginal group and 91% in the buccal group. No statistically significant difference wfound in the rate of complete abortion among both groups. The side effect profile was similar among both the groups, except for altered tain the buccal group. No statistically significant difference in patient satisfaction was observed in the groups. Clinical significance: For first-trimester medical abortion, Misoprostol can be used in various routes. The vaginal route, requires repeatevaginal examinations which becomes inconvenient for the patients. The buccal route can be used as an effective alternative to the vaginaroute.Copyright © The Author(s). 2023 Open Access.

Syed Yahiya, Y. (2022). "Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids." Drugs 82(15): 1549-1556.
	An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo ® ; Myfembree ® ) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids. (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Sylvain, B. and C. Francois (2023). "Surgical and Percutaneous Image-guided Therapies of Abdominal Wall Endometriosis: a Systematic Review of Current Evidences."
	
Sylvain, B. and C. François (2024). "Cryoablation of soft tissue tumors: a systematic review and meta-analysis."
	
Symons, R., et al. (2022). "Rates of paclitaxel hypersensitivity reactions using a modified Markman's infusion protocol." Asia-Pacific Journal of Clinical Oncology 18(Supplement 3): 142.
	Aim: Markman's desensitisation protocol allows successful retreatment of patients who have significant paclitaxel hypersensitivity reactions (PHR)1.We assessed the rates of PHRusing a modified Markman's protocol in patients with gynaecological malignancies receiving paclitaxel.By introducing this protocol,we aimed to reduce the risk and severity of PHR and save time. Method(s): We evaluated all patients receiving paclitaxel before (December 2018-September 2019) and after (October 2019-July 2020) the implementation of a modified Markman's protocol. The pre-implementation group received paclitaxel infused with a gradual titration rate from 60 ml/h to 180 ml/h. The post-implementation group received paclitaxel infused via 3 fixed-dose infusion bags (Bag 1: paclitaxel 2 mg in 100 ml saline over 30 min, Bag 2: paclitaxel 10 mg in 100 ml saline over 30 min, Bag 3: remainder of paclitaxel dose in 500 ml saline over 3 h) in the first two cycles. Rates of PHRwere compared. The cost was also compared. Result(s): A total of 426 paclitaxel infusions were administered to 78 patients. Median age was 64 years (range 34-81), and most had ovarian cancer (49%, n = 38/78). The rate of PHR was 8% (n = 16/195) versus 9% (n = 20/231) before and after implementation (p = 0.87). Most PHR occurredwithin the first 30 min in both groups (pre- vs postimplementation, 88% [n = 14/16] vs 75% [n = 15/20]; p = 0.45), and were Grade 2 in severity (pre- vs post-implementation,81%[n=13/16] vs 75% [n = 15/20]; p = 0.37). There was one Grade 3 PHR in pre-implementation group. All patients were successfully rechallenged in the post-implementation group compared to 81% (n = 13/16) in pre-implementation group (p = 0.43). The modified Markman's protocol cost at least $100/cycle more for the first two cycles than the pre-implementation protocol. Conclusion(s): The modified Markman's desensitisation protocol as a prophylaxis measure did not reduce the PHR rate although all patients were successfully rechallenged.

System Atlantic, H. (2023). Absorbable Suture vs Permanent Suture in Sacrospinous Ligament Suspension.
	No Results Available Other: Absorbable Suture and Permanent Suture Pelvic Organ Prolapse Quantification (POP-Q) exam Point C|Prolapse Recurrence|PGI-I|Suture-related Complications Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Treatment 1963079-1 January 2024

Szeliga, A., et al. (2022). "The influence of estro-progestin therapy on neurohormonal activity in functional hypothalamic amenorrhea." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(11): 997-1002.
	Background: Functional hypothalamic amenorrhea (FHA) is a chronic endocrine disorder caused by the abnormal pulsatile secretion of neurohormones in the hypothalamus. Secretion of GnRH is regulated by kisspeptin/neurokinin B/dynorphin (KNDy) neurons. These neurons produce, among other neurohormones, neurokinin B (NKB) which regulates the coordinated stimulation or inhibition of GnRH secreting neurons. Aim of the study: Assessment and comparison of serum NKB in patients with FHA at baseline, and following 6 months of estrogen-progestagen therapy. Materials and methods: Fifty-five patients with functional hypothalamic amenorrhea were included in the study group. Serum concentrations of neurokinin B (NKB), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-β-estradiol (E2), prolactin (PRL), cortisol, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), fasting glucose and insulin, as well as lipid profile were measured at baseline. At the time of diagnosis, patients with FHA were prescribed a course of 2 mg 17-β-estradiol and 10 mg dydrogesterone for duration of 6 months. Serum NKB was then reassessed following treatment at 6 months. Results: At baseline, the FHA group was found to have a decreased serum NKB concentration when compared to a healthy control group. Following 6 months of sequential estrogen-progestogen hormone therapy, this study did not find any statistically significant difference in serum NKB concentration in the treatment arm compared to baseline. Conclusions: For the first time, NKB secretion has been studied in patients with FHA. A significantly lower level of serum NKB was observed in these patients at baseline, when compared to a control group. After 6 months of combination estrogen-progesterone therapy, no significant changes in NKB levels were observed in these patients. These findings, for the first time in the literature, provide insight into the perceived benefit of HRT, calling into question its benefit in addressing the underlying etiopathogenetic contributors of FHA. These new findings may contribute to more targeted and appropriate treatment of such patients in the future.

Szmidt, M. K., et al. (2023). "Adherence to the Mediterranean Diet in Women and Reproductive Health across the Lifespan: A Narrative Review." Nutrients 15(9): 2131.
	The Mediterranean diet (MD) has been previously proven to have various health-related benefits; however, its effect on women's reproductive health over a lifespan is yet to be summarized. This study aimed to summarize the evidence-based knowledge regarding the association between the MD and selected reproductive health outcomes. By searching PubMed, ScienceDirect, and Google Scholar databases, as well as reference lists, 21 studies were included in this narrative review. The available evidence was very limited; however, there is some suggestion that higher adherence to the MD may be positively associated with a lower risk of early age menarche (1 study) and shorter menstrual cycles (1 study), but is unrelated to dysmenorrhea (1 study). Moreover, no study to date has examined the relationship between the MD and the onset age of natural menopause. Considering reproductive health diseases, there was limited evidence that a higher adherence to the MD was associated with a lower risk of premenstrual syndrome (1 study), an improvement in sexual health and a lower prevalence of sexual dysfunction (3 studies), and an improvement in the general condition of with endometriosis and the pain they can experience (1 study). The largest number of studies were found for polycystic ovarian syndrome (PCOS; 7 studies) and infertility (6 studies). Results showed that a higher adherence to the MD was associated with a lower risk of infertility, while results for PCOS were unclear, but mostly indicated a beneficial trend. Further investigations are necessary to establish the role of adherence to the MD in reproductive health maintenance and its possible role in the prevention and treatment of reproductive health diseases in women.Copyright © 2023 by the authors.

Sznurkowski, J. J., et al. (2022). "WILL CENTRALIZATION OF OVARIAN CANCER TREATMENT BE BENEFICIAL IN POLAND ?" International Journal of Gynecological Cancer 32(Supplement 2): A478.
	Introduction Background Ovarian cancer mortality in Poland is over 15% higher than the average for the European Union. A postulated way to improve prognosis for polish ovarian cancer patients is the centralization of treatment in existing certified high-volume centers. However, Danish experience has shown that such organizational changes do not affect the survival. On the other hand, American studies suggest a huge benefit from centralization of treatment. Aim(s): To compare overall survival of advanced ovarian cancer patients treated in high and low volume centers in voivodeship with mean national mortality rate Methods Data on reimbursement of treatment modalities of advanced ovarian cancer patients treated consecutively between 2012 -2019 in the Pomeranian Voivodeship were retrieved from the database of the National Health Fund and data on overall survival (OS) from the Polish National Cancer Registry. OS curves were estimated by the Kaplan-Meier method. P-values of <0.05 were significant. Results 693 of 2015 identified C56 cases, were excluded due to reimbursement of surgical treatment only (suggesting early cancer stage or borderline). From remained 1322 cases, 57 were excluded due to unappropriated chemotherapy, leaving finally the group of similarly treated 1265 advanced C56 patients.Treatment of 1265 advanced C56 patients (surgery + chemotherapy +/-Bev) was conducted in 21 centers. Two of them were high-volume (ESGO certified: UCK & GCO with mean number of 52 cases annually) and 19 were low-volume (with mean number of 2 cases annually). 953/1265 (75.34%) and 312/1265 (24.66%) patients were treated in high and low-volume centers respectively. Conclusions Centralization of treatment in existing certified high-volume centers will not improve prognosis of advanced C56 patients. Treatment volume of the center seems to be unapropriate measure of the quality of treatment in Poland.

Szubert, M., et al. (2021). "Adenomyosis and infertility-review of medical and surgical approaches." International Journal of Environmental Research and Public Health 18(3): 1-12.
	The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although adenomyosis is detected more often in women of late reproductive age, its influence on pregnancy rates is important, especially considering the tendency to delay pregnancy among women in developed countries. In this article, we present a critical analysis of the literature data concerning the impact of adenomyosis on fertility. The possible effects of treatment on the pregnancy rate will also be discussed. We conducted a literature search; publications from Pubmed, Embase and Cochrane databases published from 1982 to 2019 were retrieved using terms 'adenomyosis and infertility' and 'adenomyosis and pregnancy outcomes', extensively studied in the aspects of diagnosis, pathogenesis of infertility and possible treatment methods. Molecular studies have given deep insight into the pathogenesis of adenomyosis in the recent few years, but there is a huge discrepancy between in vitro studies and praxis. Oral contraceptive pills, anti-prostaglandins, oral or parenteral progestins, danazol and gonadotrophin-releasing hormone (GnRH) analogues have all been used to control menstrual pain and menorrhagia in women with adenomyosis, but they temporarily suppress the menstrual cycle. Additionally, endometrial ablation and hysterectomy used to alleviate pain caused by adenomyosis exclude pregnancy planning. The development of imaging techniques-ultrasound and MRI-enables the diagnosis of adenomyosis with very high accuracy nowadays, but the methods of treatment mentioned above have not given satisfactory results in women planning pregnancy. For these patients, the high-intensity-focused ultrasound method (HIFU) and combined treatment before assisted reproductive techniques can prove beneficial in adenomyosis patients.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Szydłowska, I., et al. (2021). "Effects of probiotics supplementation on the hormone and body mass index in perimenopausal and postmenopausal women using the standardized diet. A 5-week double-blind, placebo-controlled, and randomized clinical study." European Review for Medical and Pharmacological Sciences 25(10): 3859-3867.
	OBJECTIVE: The results of pioneering studies indicate that probiotics can alleviate menopausal symptoms (including cardiometabolic dysfunctions) and improve the quality of life of perimenopausal/postmenopausal women. However, the results of randomized control trials are scarce to evaluate whether the administration of probiotics could affect the balance of sex hormones during the menopause period. PATIENTS AND METHODS: In this randomized, double-blind, and placebo-controlled study, 48 perimenopausal and postmenopausal women received multispecies probiotic Sanprobi Barrier in a dose of 2.5 × 109 (CFU) for five weeks. Dietary guidelines were introduced in both groups simultaneously (~1800 kcal/per day, whole grain, no-wheat meals). The study aimed to assess the variations in follicle-stimulating hormone (FSH), estradiol (E2), cortisol (as the hypothalamic-pituitary-ovarian axis hormone), and the body mass during the intervention. RESULTS: At the endpoint, FSH level has increased significantly concerning the baseline after the probiotic intake (31.91 vs. 42.00 mIU/ml; p < 0.009). Also, in the placebo group, a strong trend to elevate FSH was observed (22.31 vs. 41.99 mIU/ml; p = 0.055). Body mass has crucially decreased in reference to the baseline in both groups (PRO: 27.90 vs. 26.30 kg/m2, p<0.001; PBO: 25.90 to 24.60 kg/m2, p<0.001). CONCLUSIONS: Probiotics affect FSH levels in perimenopausal women while simultaneously representing a non-invasive strategy to impact hormonal homeostasis. They could potentially have an impact on cardiometabolic health.

Szymanowski, P., et al. (2022). "The impact of cystocele repair on urge symptoms in women with pelvic organ prolapse." Ginekologia polska.
	Objectives: The purpose of this study was to evaluate the impact of cystocele repair on urinary urge symptoms and to determine the likelihood that urge symptoms are caused by cystocele and therefore cured by cystocele repair. The secondary aim was to assess the impact of baseline cystocele stage POP on the improvement of urge symptoms following surgical treatment of POP.; Material and Methods: A total of 321 female patients with cystocele stages II, III or IV (POP), who underwent repair surgery for pelvic organ prolapse, were included. A retrospective analysis was performed to determine the presence of urge symptoms in patients with cystocele and to evaluate how many patients were cured from urge symptoms by the cystocele repair. Postoperative data were obtained by interview during a follow-up examination six weeks after surgery.; Results: Preoperatively, 52.02% of all patients diagnosed with cystocele stages II, III or IV POP experienced urge symptoms. Urge symptoms were cured in 88.62% of patients with cystocele stages II after POP repair (p < 0.005). 88.60% of patients with cystocele stage II POP and 88.68% of patients with cystocele stages III to IV POP reported improvement in urge symptoms (p < 0.005). Despite cystocele repair, 11.4% of patients with preoperative cystocele stage II POP and 11.32% with preoperative cystocele stages III and IV POP reported persistent urge symptoms. 5.84% of the study group who showed no urge symptoms preoperatively, experienced de novo urge symptoms after following surgery (p < 0.005).; Conclusions: Cystocele repair cured urge symptoms in the majority of patients. Therefore, repair of bladder prolapse may help to differentiate urge symptoms from other urinary tract dysfunctions and assist in determining a proper diagnosis and treatment. However, the severity of POP had no significant influence on the improvement in urge symptoms following cystocele repair. Risk of de novo urge symptoms after anatomical repair still needs to be explored.

Szymanowski, P., et al. (2021). "Preperitoneal laparoscopic lateral repair in pelvic organ prolapse - a novel approach." Ginekologia polska.
	OBJECTIVES: The aim of this study is to present a novel approach for a paravaginal defect treatment. This extraperitoneal approach can be performed in patients with comorbidities and on obese patients. The main advantages are: not requiring the pneumoperitoneum and the Trendelenburg position and the avoidance of peritoneal adhesions. MATERIAL AND METHODS: This study presents the results in 27 patients with cystocele caused by a lateral defect pelvic organ prolapse quantification (POP Q) stage II or higher. The procedure was performed with a modified Richardson and Burch technique using a preperitoneal approach. Three follow-up examinations were conducted two, six weeks, and six months after the operation. A quality of life assessment was conducted before and after surgery using the short form of the PFIQ-7. RESULTS: All patients had a POP Q II cystocele and 59% had concomitant stress urinary incontinence. In all patients cystocele was reduce to asymptomatic POP Q stage I or 0. Mean operation time was approximately 80 minutes. In six months post-operation follow up, one case of recurrence was noted. The patients' quality of life revealed a statistical improvement from an average of 6.8 points before, to an average of 0.7 points after the operation (p < 0.05) in the PFIQ-7. CONCLUSIONS: Preperitoneal laparoscopic lateral repair is a relatively fast procedure and it is also feasible for obese women and for patients with a cardiopulmonary risk. Neither the Trendelenburg position nor the pneumoperitoneum are required. Postoperatively, the patients witnessed a reduction of the cystocele and complaints connected with their previous condition.

Szymczak, P., et al. (2019). "Comparison of laparoscopic techniques for apical organ prolapse repair - a systematic review of the literature." Neurourology and Urodynamics 38(8): 2031-2050.
	Aims: Apical defect is a pelvic organ prolapse disorder, with 5%-15% prevalence. The aim of the study was to investigate methods of laparoscopic repair of apical defect and compare them with other techniques (open, vaginal, and robotic).; Methods: A systematic search of the literature was conducted in MEDLINE/PubMed and ClinicalTrials.gov databases using the following key words: apical prolapse and treatment procedures. The search was limited by using the humans filters. Only articles published in English between 2010 and 2018 were considered. Two independent authors reviewed the publications for inclusion on the basis of the following criteria: (a) use of laparoscopic techniques, and (b) apical support loss as indication for surgery.; Results: A total of 1002 papers were initially identified; 24 studies fulfilled the inclusion criteria. Four main laparoscopic procedures were found. The reported anatomical success rate (POP-Q < II stage) was 77%-100%, with patient satisfaction for pectopexy, laparoscopic sacropexy (LS), lateral ligament suspension and laparoscopic uterosacral ligament suspension (LUSLS) of 96.4%-97.6%, 71.0%-100%, 66.7%-87.8%, and 95%-95.5%, respectively. Major complications included hemorrhage, bladder, ureter, and/or bowel injuries were rare. Prolapse recurrences after LUSLS and LS were reported in 13.2% and 10.4% of patients, respectively; with reoperation rate for LS 2.2%-12.8%.; Conclusions: Most studies reported anatomical and subjective outcomes, with follow-up ranging from 1 month to >7 years. Success rates for laparoscopic and abdominal corrections of apical defect were similar; laparoscopy was superior in terms of perioperative blood loss, length of hospital stay, and recovery. (© 2019 Wiley Periodicals, Inc.)

Tabatabaie, M., et al. (2022). "The effect of Myo-Inositol supplement on molecular regulation of folliculogenesis, steroidogenesis, and assisted reproductive technique outcomes in patients with polycystic ovarian syndrome." Molecular biology reports 49(2): 875-884.
	Research question: The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear. Design(s): Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3beta-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation. Result(s): Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1. Conclusion(s): Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Tabitha, P., et al. (2021). "Psychological interventions for menopause: a meta-analysis of psychological outcomes."
	
Tabuyo-Martin, A., et al. (2022). "Palliative medicine referral and end-of-life interventions among minority patients with advanced or metastatic gynecologic cancer (433)." Gynecologic Oncology 166(Supplement 1): S218.
	Objectives: Referral to palliative medicine (PM) has been shown to improve quality of life, reduce hospitalizations, and improve survival. Few data exist about palliative medicine approaches in the minority gynecologic oncology (GYO) patients. Our objective was to assess differences in palliative medicine referrals and end-of-life interventions by race and ethnicity in a diverse population of GYO patients. If such differences exist, they may inform subsequent interventions for care optimization and elimination of structural barriers. Method(s): A retrospective cohort study of patients receiving gynecologic oncology care at a tertiary referral center between 2017 and 2019 was conducted. Patients had either metastatic disease at the time of diagnosis or recurrence. Demographic and clinical data were retrospectively abstracted. Analysis was done with Chi-square (or Fisher's exact) and t-tests. Tests were two-sided with significance set at a p-value of <.05. Result(s): A total of 186 patients met the inclusion criteria. The mean age was 58 years (+/-12.971). Underrepresented minorities accounted for 47.3% of the cohort. English was identified as the primary language for 69.9% of the patients with Spanish reported in 24.2%. Over 90% of patients had insurance coverage. Ovarian cancer (37.6%) and uterine cancer (32.8%) were the most common sites of origin. The majority of patients (75%) had an advanced stage at the time of diagnosis. Referral to PM at any point during the study time frame occurred in 82 (44.2%) patients; 31% of patients were referred <90 days prior to death. Symptom management was the most common indication for referral (73.1%). Higher medication use for symptom control (pain, nausea, etc.) was more common among those referred. ED visits and hospitalizations were also higher among those referred to PM, with over 50% having >=4 visits through their entire cancer care. Lastly, 30% of the patients expired during the study period without a PM referral. Black patients were noted to have a higher appetite stimulant use compared to White patients (19 [41%] vs 34 [24%], respectively [p=0.027]). Black patients were also noted to have a higher number of ED visits, with 26.1% having seven or more, compared with 10.7% for White (p=0.035). Lastly, chemotherapy in the last 30 days of life was also higher among Black patients compared to White (7 [15.2%] vs 6 [4.3%], respectively [p=0.049]). Conclusion(s): Despite the known benefits of palliative care, over 50% of patients in this gynecologic oncology cohort with advanced or recurrent malignancy were not referred. Race was associated with variation in interventions near end-of-life. Further research is needed to better identify priorities for interventions, especially as they relate to the care of patients from underrepresented minority groups.Copyright © 2022 Elsevier Inc.

Tabuyo-Martin, A., et al. (2023). "Palliative Medicine Referral and End-of-Life Interventions Among Racial and Ethnic Minority Patients With Advanced or Recurrent Gynecologic Cancer." Cancer Control 30.
	Background: Referral to palliative medicine (PM) has been shown to improve quality of life, reduce hospitalizations, and improve survival. Limited data exist about PM utilization among racial minorities with gynecologic malignancies. Our objective was to assess differences in palliative medicine referrals and end of life interventions (within the last 30 days of life) by race and ethnicity in a diverse population of gynecologic oncology patients. Method(s): A retrospective cohort study of patients receiving gynecologic oncologic care at a tertiary referral center between 2017 - 2019 was conducted. Patients had either metastatic disease at the time of diagnosis or recurrence. Demographic and clinical data were abstracted. Exploratory analyses were done using chi-square and rank sum tests. Tests were two-sided with significance set at P <.05. Result(s): A total of 186 patients were included. Of those, 82 (44.1%) were referred to palliative medicine. Underrepresented minorities accounted for 47.3% of patients. English was identified as the primary language for 69.9% of the patients and Spanish in 24.2%. Over 90% of patients had insurance coverage. Ovarian cancer (37.6%) and uterine cancer (32.8%) were the most common sites of origin. Most patients (75%) had advanced stage at the time of diagnosis. Race and language spoken were not associated with referral to PM. Black patients were more likely to have been prescribed appetite stimulants compared to White patients (41% vs 24%, P =.038). Black patients also had a higher number of emergency department visits compared to White patients during the study timeframe. Chemotherapy in the last 30 days of life was also more likely to be given to Black patients compared to White (P =.019). Conclusion(s): Race was associated with variation in interventions and healthcare utilization near end-of-life. Understanding the etiologies of these differences is crucial to inform interventions for care optimization as it relates specifically to the health of minority patients.Copyright © The Author(s) 2023.

Tafazoli, A. and M. Othman (2023). "ASPIRIN AND ENDOMETRIAL CANCER: RE-VISITING THE ANTITHROMBOTIC/ANTI-CANCER PROPERTIES." Canadian journal of diabetes 47(7 Supplement): S212-S213.
	BACKGROUND: Endometrial cancer (EC) is among the 4 top cancers diagnosed in women and is highly thrombogenic. Cardiovascular events are among the prominent causes of death in EC patients. Aspirin is a common anti-platelet drug in cardiovascular disease but its value in cancer has only been described in a few cancer types and there is a high chance for beneficial effect of aspirin in EC. In this study, we aim to explore the literature to assess the use of aspirin in EC preventive and therapeutic regimens. METHODS AND RESULTS: Due to sparsity of data in this field we applied a narrative review style for the study. We searched the PubMed database using MeSH terms "Endometrial Neoplasms" and "Aspirin" without any limitation or filters. Studies focusing on non-steroidal anti-inflammatory drugs instead of aspirin and those with focus on all or different cancer types other than EC were excluded. Checking the references within the references also showed acceptable precision in the selected articles for this narrative exploration. Nineteen articles resulted from this search, and were divided into 4 categories including in vitro, preventive, therapeutic and review articles (Table 1). Overall, the findings for use of aspirin for prevention and adjuvant use were more abundant compared to the observations negating its use. However, three factors prevented making a clear recommendation about aspirin use in EC. First, lack of studies exclusively evaluating the cardiovascular outcomes of aspirin in EC. Secondly, a considerable number of studies were not able to find a positive effect for aspirin. However, a reassuring safety profile for aspirin was found regarding the bleeding risk during chemotherapy or surgical interventions. Thirdly, in one of the screened studies, increased mortality rate was reported for aspirin use. Specifically, the evidence to support aspirin use as an antithrombotic agent in EC is very low. CONCLUSION(S): The current evidence for the value of aspirin use in EC is sparse and limited. The results of this literature exploration can be a foundation for proposing a series of systematic investigations (Figure 1) to define the role, indications, and contraindications of aspirin therapy in EC patients with more clarity and targeted clinical and practical value. [Formula presented] [Formula presented]Copyright © 2023

Taftian, M., et al. (2022). "The Effect of Ketogenic Diet on Weight Loss in Adult Patients with Cancer: A Systematic Review and Meta-Analysis of Controlled Clinical Trials." Nutrition and Cancer 74(4): 1222-1234.
	Recently, Ketogenic diets have been investigated as an adjunct cancer treatment. This study aimed to summarize the effect of a ketogenic diet on weight in adults with cancer. Literature search was performed in PubMed/MEDLINE, Web of Science (ISI), Scopus, and Google Scholar up to August 2020. The overall estimates were calculated through a random-effects model. A total of eight trials were eligible to be included in the current study. Meta-analysis revealed that a ketogenic diet significantly reduces body weight in cancer patients [weighted mean difference (WMD) = -3.992 kg, 95% confidence interval (CI): -7.417 to 0.566, P = 0.022, n = 7]. The subgroup analysis revealed that the decreasing effect remained significant in trials done in patients with breast cancer (WMD = -3.332 kg, 95%CI: -4.169 to -2.495, P < 0.001, n = 3) and in studies with >10 (WMD = -2.795, 95%CI: -4.053 to -1.537, P < 0.001, n = 3) and <=10 weeks of duration (WMD = -7.257, 95%CI: -13.034 to -1.481, P = 0.014, n = 4). However, our findings did not support significant effect of ketogenic diets on body mass index (BMI) (WMD = -1.808 kg/m2, 95%CI: -3.945 to 0.33, P = 0.097, n = 4). In conclusion, ketogenic diets might result to a weight loss in adults with cancer. Future well-designed randomized controlled clinical trials might warrant current findings.Copyright © 2022 Taylor & Francis Group, LLC.

Tagliaferri, L., et al. (2023). "The Impact of HAPPY (Humanity Assurance Protocol in Interventional Radiotherapy) on the Psychological Well-being of Gynecological Cancer Patients." Current radiopharmaceuticals.
	Background: HAPPY (Humanity Assurance Protocol in interventional radiotherapy) reports the necessity for gynecological cancer patients to undergo interventional radiotherapy (IRT, also called brachytherapy). The present paper has evaluated how some precautions may improve the psychological well-being of the patients during IRT.; Methods: Patients with gynecological cancer undergoing IRT-HDR were analyzed. Patients answered three questionnaires before the IRT procedure (T0) and at the end of IRT (T1): Distress Thermometer (DT), Numerical Rating Scale for IRT procedure distress (NRS), and Hospital Anxiety and Depression Scale (HADS). Correlations have been calculated pairwise through pandas. corrwith with a Pearson algorithm, and the p-values have been calculated through scipy.stats.pearsonr. Plots have been generated through seaborn and matplotlib. A Wilcoxon test was used.; Results: 55 patients were selected for this study. The median age of the patients was 64 (range, 39-84) years. 52 patients were with stage I endometrial cancer, whereas 3/3 patients with cervical cancer had locally advanced stages (IIB-IVA). 26 patients had a high education level (47.3%), and 38 were married or with a partner (69.1%). Only 14/55 (25.45%) patients were working. The HADS, DT, and NRS averages before the IRT procedure (T0) were 10.2, 3.8, and 4.3, respectively. After applying the HAPPY protocol, the HADS, DT, and NRS averages after IRT (T1) were 9.4, 3.4, and 2.6, respectively. The Wilcoxon signed rank test analysis showed a significant improvement in NRS (p < 0.00001) and HADS (p = 0.034). Living with a partner, parents or relatives was the only parameter statistically significantly associated with better DT pre-IRT (p = 0.04), HADS pre-IRT (p = 0.01), DT post-IRT (p = 0.01), and HADS post-IRT (p = 0.04).; Conclusion: In our study, the HAPPY protocol was associated with a significant reduction in patients' distress, anxiety, and discomfort. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tagliaferri, V., et al. (2022). "Laparoscopic sacrocolpopexy versus pelvic organ prolapse suspension for surgical management of pelvic organ prolapse: a retrospective study." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(6): 2075-2081.
	This retrospective surgical clinical study compares clinical and functional effects of laparoscopic sacrocolpopexy (LSC) and laparoscopic pelvic organ prolapse suspension (L-POPS) for anterior and central prolapse correction. Thirty patients enrolled were affected by a symptomatic vaginal central compartment stage 2-3 prolapse and vaginal anterior compartment stage 1-3 prolapse without vaginal posterior compartment prolapse. A successful correction of anterior and central compartments prolapse without relapses were observed in both groups (LSC group versus L-POPS group). In patients who underwent L-POPS, a de novo posterior compartment prolapse was recorded. In this group, 7/15 patients complained more bowel symptoms and underwent vaginal colpoperineoplasty. In 20% (group LSC) and in 13.3% (group L-POPS) of cases, a condition of de novo urinary stress incontinence was described. LSC seems to remain the gold standard for pelvic organ prolapse correction, while further preventive strategies should be carried out in L-POPS to avoid a de novo posterior compartment prolapse.Impact Statement What is already known on this subject? Laparoscopic sacrocolpopexy is the gold standard technique for the correction of pelvic organ prolapse; however, laparoscopic pelvic organ prolapse suspension, based on the surgical technique of lateral suspension, is an innovative surgical method for the treatment of POP. What do the results of this study add? L-POPS could be considered a valid alternative to LSC for women with multiple comorbidities because of less operative time and reduced surgical risks. However, in the long follow-up period, some patients underwent L-POPS complained rectal discomfort and dysfunction on quality of life questionnaire and on clinical evaluation from six to twelve months after surgery probably due to the post-operative appearance of posterior compartment prolapse. What are the implications of these findings for clinical practice and/or further research? Considering the retrospective design and the small sample size the major limits of this study, larger, prospective, randomized studies could be encouraged to better compare a modified technique of L-POPS with posterior mesh apposition (preventing the post-operative appearance of posterior compartment prolapse) with the gold standard LSC for the correction of multi-compartment POP.

Taguchi, A., et al. (2023). "Heterogeneous treatment effects of adjuvant therapy for patients with cervical cancer in the intermediate-risk group." Cancer Medicine 12(18): 18557-18567.
	Background: The efficacy of adjuvant therapy for patients with cervical cancer with intermediate risk (CC-IR) remains controversial. We examined the impact of adjuvant therapy on survival outcomes in patients with CC-IR and evaluated the heterogeneous treatment effects (HTEs) of adjuvant therapies based on clinicopathologic characteristics.; Methods: We retrospectively analyzed a previous Japanese nationwide cohort of 6192 patients with stage IB-IIB cervical cancer who underwent radical hysterectomy. We created two pairs of propensity score-matched treatment/control groups to investigate the treatment effects of adjuvant therapies: (1) adjuvant therapy versus non-adjuvant therapy; (2) chemotherapy versus radiotherapy conditional on adjuvant therapy. Multivariate analyses with treatment interactions were performed to evaluate the HTEs.; Results: Among the 1613 patients with CC-IR, 619 and 994 were in the non-treatment and treatment groups, respectively. Survival outcomes did not differ between the two groups: 3-year progression-free survival (PFS) rates were 88.1% and 90.3% in the non-treatment and treatment groups, respectively (p = 0.199). Of the patients in the treatment group, 654 and 340 received radiotherapy and chemotherapy, respectively. Patients who received chemotherapy had better PFS than those who received radiotherapy (3-year PFS, 90.9% vs. 82.9%, p = 0.010). Tumor size was a significant factor that affected the treatment effects of chemotherapy; patients with large tumors gained better therapeutic effects from chemotherapy than those with small tumors.; Conclusion: Adjuvant therapy is optional for some patients with CC-IR; however, chemotherapy can be recommended as adjuvant therapy, particularly for patients with large tumors. (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Taha, K., et al. (2023). "PARP inhibitors in advanced urothelial carcinoma - A systematic review of efficacy and safety."
	
Taheri, M., et al. (2019). "Nonresective treatments for uterine fibroids: a systematic review of uterine and fibroid volume reductions." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 36(1): 295-301.
	Patients are increasingly seeking uterus-preserving, minimally invasive treatments for symptomatic uterine fibroids. This has led to a greater use of nonresective treatments such as uterine artery embolization (UAE), focused ultrasound (FUS) and more recently, radiofrequency ablation (RFA) of fibroids. This systematic review, following PRISMA guidelines, examines the change in uterine and fibroid volumes associated with UAE, FUS, and RFA. Pubmed and MedlinePlus databases were searched from 1956 to 2016. The keywords used were 'radiofrequency ablation,' 'magnetic resonance guided focused ultrasound,' 'ultrasound guided focused ultrasound', 'uterine artery embolization,' 'uterine fibroid embolization,' and 'leiomyoma' or 'fibroid'. Publications with at least 20 patients were included. Data were collected and analyzed using Microsoft Excel ® (Microsoft Corporation, Redmond, WA) software. Eighty-one relevant papers were identified: 52 related to UAE, 11 to RFA, 17 to FUS, 1 compared UAE and FUS. We report the published uterine volume and fibroid volume changes seen in these studies at 1 to 36 months. The pooled fibroid volume reductions at six months seen with RFA were 70%, UAE 54% and FUS 32%. All three types of nonresective treatment result in fibroid volume reduction. However, fibroid volume reduction is most marked with RFA, with UAE resulting in the next most volume reduction. Additional larger cohort studies, including those that are randomized and/or comparative, would enable definitive conclusions. This is the first systematic review comparing uterine and fibroid volume reduction after RFA, UAE and MRgFUS.

Tahtali, I. N., et al. (2022). "The new therapeutic option for female stress and stress-predominant mixed urinary incontinence: Periurethral hypertonic saline (10%) injection." LUTS: Lower Urinary Tract Symptoms 14(3): 186-192.
	Objectives: We aimed to evaluate the safety and efficacy of periurethral hypertonic saline (10% NaCl) injection in the treatment of stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (S-MUI) in women. Method(s): This was a prospective study conducted between January 2014 and April 2018 with 64 women (44 SUI and 21 S-MUI). Patients with SUI and S-MUI were evaluated using the Urinary Distress Inventory 6. Quality of life was evaluated with the Incontinence Quality of Life Scale and lower urinary tract symptoms of the women were evaluated with the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules. Incontinence status and treatment success were assessed via the Stamey incontinence grade and pad test. Result(s): The subjective success rate was 58.5%, and the objective success rate was 81.5%. The rate of reinjection was 21.5%, and the mean duration of reinjection was 8.92 months (3-19 months). Minor adverse effects were observed in 30.4% of the 79 injections. International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules and Incontinence Quality of Life Scale scores improved remarkably starting from the first month. Urinary Distress Inventory 6 scores in the S-MUI group also improved. Conclusion(s): The results indicate that hypertonic saline injection is an effective and safe method in the treatment of SUI and S-MUI. Since hypertonic saline is a much cheaper and more accessible substance compared to bulking agents, it seems to be a viable alternative for urinary incontinence treatment in women.Copyright © 2021 John Wiley & Sons Australia, Ltd.

Taieb, J., et al. (2021). "Safety and efficacy of trifluridine/tipiracil in previously treated metastatic colorectal cancer: final results according to duration of treatment from the phase IIIb, international, open-label, early-access PRECONNECT study." Annals of Oncology 32: S210.
	Background: Trifluridine/tipiracil (FTD/TPI) is registered in over 93 countries for the management of patients with metastatic colorectal cancer (mCRC) who have progressed on standard therapies. In the RECOURSE study, FTD/TPI significantly improved overall survival and progression‐free survival (PFS) compared with placebo. 1,2 PRECONNECT was an international, multicentre, open‐label, phase IIIb trial (NCT03306394) designed to provide eligible adults with mCRC access to FTD/TPI and to further characterise the safety and efficacy of FTD/TPI in daily clinical practice. Here we present the final results from PRECONNECT according to duration of treatment (DoT). Methods: Patients aged ≥18 years with histologically confirmed mCRC who were refractory to, or not candidates for, standard chemotherapies and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, received oral FTD/TPI 35 mg/m 2 twice‐daily on days 1‐5 and 8‐12 of each 28‐day cycle. Treatment continued until disease progression, unacceptable toxicity, physician decision, withdrawal of consent, pregnancy, major protocol deviation, or when FTD/TPI became commercially available. The primary endpoint was safety (including incidence of treatment‐emergent adverse events [TEAEs] and time to deterioration of ECOG PS to ≥2). Secondary endpoints included PFS and quality of life (QoL) as measured by QLQ‐C30. Data are presented as descriptive statistics, and by DoT group – [0‐3] FTD/TPI treatment cycles completed, [4‐7] cycles completed and ≥8 cycles completed. Results: Of the 914 patients (male 59%; median age 62 years; ECOG PS 0 in 49%; RAS mutant 52%; median time from first metastasis 32 months; median number of previous lines of treatment 3) analysed, 632 (69%) completed [0‐3] cycles, 219 (24%) completed [4‐7] cycles, and 63 (7%) completed ≥8 cycles. Patients completing [4‐7] and ≥8 cycles of FTD/TPI were more likely to have a baseline ECOG PS of 0, less likely to have a RAS mutation, had a longer time from first metastasis to first FTD/TPI intake, and were less likely to have previously received regorafenib versus those completing [0–3] cycles. TEAEs were experienced by 96.6% of the overall patient population; the most frequent were neutropenia (53.5%), asthenia (36.7%), anaemia (31.1%), nausea (29.5%), and diarrhoea (24.8%). Drug‐related grade ≥3 TEAEs included neutropenia (38.1%), anaemia (7.2%), and asthenia (3.4%). Severe febrile neutropenia (1.2%) and severe cardiac disorders (0.7%) were infrequent. Median [95% CI] PFS was 2.8 [2.7‐3.0] months, and median PFS increased with DoT ([0‐3] cycles: 2.2 [2.0‐2.3] months; [4‐7] cycles: 5.3 [4.6‐5.6] months; ≥8 cycles: 9.4 [8.7‐10.5] months). Median [95% CI] time to ECOG PS deterioration was 9.2 [8.5‐NC] months and increased with DoT ([0‐3] cycles: 3.8 [3.5‐3.9] months; [4‐7] cycles: 8.9 [8.5‐NC] months; ≥8 cycles: 16.4 [14.3‐NC] months). There was no clinically relevant change from baseline in QLQ‐C30‐GHS score overall or by DoT group. Conclusions: The PRECONNECT study showed consistent results with the previously demonstrated safety and efficacy profile of FTD/TPI, with no new safety concerns identified. PFS and time to ECOG PS deterioration increased with DoT, and QoL was maintained during treatment. These data provide additional support for the use of FTD/TPI in the treatment of mCRC in daily clinical practice. Clinical trial identification: NCT03306394. Editorial acknowledgement: We wish to thank the patients who participated in this study and their families. We would also like to thank the PRECONNECT investigators who included the patients in the analyses described. Editorial assistance was provided by Martin Gilmour, PhD, CMPP of Empowering Strategic Performance (ESP) Ltd, funded by Servier. Legal entity responsible for the study: The authors. Funding: The PRECONNECT study was sponsored by Institut de Recherches Internationales, Servier, France. Disclosure: T. Price: Honoraria (self): Servier, Merck. L. Vidot: Ful Part‐time employment: Institut de Recherches Internationales Servier. A. Raimond‐Thibaut: Full / Part‐time employment: Servier. H. Chrostek: Full / Part‐time employment: Servier. J. Bachet: Honoraria (self): Servier, Amgen, Merck Serono, Sanofi, Roche, Pierre Fabre; Advisory / Consultancy: Servier, Amgen, Merck Serono, Pierre Fabre; Travel / Accommodation / Expenses: Servier, Amgen, Merck Serono, Sanofi, Roche. A. Falcone: Honoraria (self): Amgen, Lilly, Merck, Roche, Servier; Advisory / Consultancy: Amgen, Bayer, Bristol‐Myers Squibb, Lilly, Merck, Roche, Servier; Research grant / Funding (institution): Amgen, Bayer, Merck, MSD, Roche, Sanofi, Servier; Travel / Accommodation / Expenses: Amgen, Bayer, Merck, Roche, Servier. All other authors have declared no conflicts of interest.

Tait, D. L., et al. (2021). "Comparison of Perioperative Outcomes between Minimally Invasive Sentinel Node Biopsy and Full Lymphadenectomy for Endometrial Cancer." Journal of Minimally Invasive Gynecology 28(8): 1514-1518.
	STUDY OBJECTIVE: To review the perioperative differences between patients undergoing a minimally invasive sentinel lymph node dissection and those undergoing a full lymphadenectomy. DESIGN: Retrospective review. SETTING: Teaching hospital. PATIENTS: All patients undergoing a minimally invasive procedure for endometrial cancer that included nodal evaluation. INTERVENTIONS: Patients who underwent a sentinel lymph node biopsy were compared with those who underwent a full lymphadenectomy at the time of minimally invasive surgery by either laparoscopic or robot-assisted surgery. MEASUREMENTS AND MAIN RESULTS: A total of 241 minimally invasive surgery procedures for endometrial cancer were performed during the 20-month study period. Nodal dissection was indicated and performed in 156 (65%) of these patients, with 93 undergoing a sentinel lymph node biopsy and 63 a full lymphadenectomy. There was no difference between the sentinel group and the lymphadenectomy group with respect to age, estimated blood loss (p = .23), use of a preoperative enhanced recovery after surgery program (p = .82), or body mass index (34.0 kg/m2 vs 33.7 kg/m2; p = .87). The use of full lymphadenectomy was very dependent on the surgeon (p <.001). There was no difference in narcotic use in milligram intravenous equivalents of morphine in surgery (20.9 vs 22.2; p = .37), recovery (4.6 vs 4.9; p = .73), or total dose (25.4 vs 27.0; p = .33). The surgical procedure was longer with lymphadenectomy (185.2 minutes vs 214.2 minutes; p <.001) and the relative risk of discharge from recovery was lower (0.71; 95% confidence interval, 0.51-0.97; p = .03). The hospital stay was longer with lymphadenectomy (16.3 hours vs 25.5 hours; p <.001) and same-day discharge less frequent (48.5% vs 13.8%; p <.001). A multivariate analysis confirmed that sentinel node biopsy was associated with an increased relative risk of discharge of 1.68 (95% confidence interval 1.11-2.53; p = .01) CONCLUSION: Total narcotic requirements are similar between sentinel node biopsy and lymphadenectomy. However, sentinel node biopsy is associated with a shorter surgical time, recovery time, and hospital stay.

Taithongchai, A., et al. (2024). "Oestrogen therapy for preventing pelvic organ prolapse in postmenopausal women." Cochrane Database of Systematic Reviews 2024(2): CD015695.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects of local and systemic oestrogen therapy in preventing pelvic organ prolapse in postmenopausal women.Copyright ©2024The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Takacs, P., et al. (2023). "A Randomized Controlled Trial to Assess the Effectiveness of a Specially Formulated Food Supplement and Pelvic Floor Muscle Training in Women with Stress-Predominant Urinary Incontinence." Obstetrics and Gynecology 141(5 Supplement 1): 23S.
	INTRODUCTION: The objective of this study was to assess the effectiveness of a creatine-leucine-based food supplement and standardized pelvic floor muscle training (PFMT) in women with stress-predominant urinary incontinence (SUI). METHOD(S): Women with SUI were randomized to receive daily oral supplementation for 6 weeks with either a supplement or placebo. Both groups were instructed to perform daily PFMT at an intensity of at least 75% of one repetition maximum of 45 pelvic floor muscle contractions per day. The primary outcome was the Urogenital Distress Inventory Short Form (UDI-6) score. Secondary outcomes were the Incontinence Impact Questionnaire (IIQ-7) score, Biomechanical Integrity (BI) score measured by Vaginal Tactile Imager. To have a power of 80% and a significance level of 5%, a sample size of 32 was needed. The trial was IRB approved. RESULT(S): Within-group analysis showed that UDI-6 and IIQ-7 scores improved significantly from baseline to 6 weeks in the treatment group but not in the control group (UDI-6 score [mean6SD], 45621 versus 29621, P 5.02; 43618 versus 33626, P 5.22) (IIQ-7 score [mean6SD], 50630 versus 30621, P5.01; 48623 versus 40628, P 5.36). Out of the 52 examined VTI parameters, significantly more parameters improved in the treatment group compared to the control group (11/52 versus 3/52, P 5.04). BI-score, on average, improved significantly in the treatment and control group as well (SD unit, mean, from 21.06 to 20.58, P 5.001; from 20.66 to 20.42, P 5.04). CONCLUSION(S): Women with SUI receiving a specially formulated supplement in addition to daily PFMT for 6 weeks had improved urinary symptoms (significant decrease in UDI-6 and IIQ-7 scores) and better BI score compared to baseline.

Takahashi, K., et al. (2020). "A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial)." Medicine 99(32): e21457.
	Introduction: Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol.; Methods/design: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response.; Discussion: The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab.; Trial Registration: This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150.

Takahashi, S., et al. (2022). "Efficacy of mirabegron, a beta3-adrenoreceptor agonist, in Japanese women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence: Post-hoc analysis of pooled data from two randomized, placebo-controlled, double-blind studies." International Journal of Urology 29(1): 7-15.
	Objective: To confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo. Method(s): Post-hoc analyses were carried out using pooled data from a Japanese phase IIb and a phase III study. The primary efficacy end-point was baseline to end-of-treatment change in the mean number of micturitions/24 h. The secondary end-points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24 h, and mean number of nocturia episodes/night. Other end-points were quality of life and incontinence normalization rates. Result(s): Women with urgency urinary incontinence (placebo n = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included. Change in mean micturitions/24 h at end-of-treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end-points, median changes for mirabegron were statistically significant versus placebo at end-of-treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population. Mirabegron showed larger improvements versus placebo in all quality-of-life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo. Conclusion(s): Mirabegron 50 mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.Copyright © 2021 Astellas Pharma Inc. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association

Takahashi, S., et al. (2022). "Efficacy of mirabegron, a β3 -adrenoreceptor agonist, in Japanese women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence: post-hoc analysis of pooled data from two randomized, placebo-controlled, double-blind studies." International Journal of Urology 29(1): 7‐15.
	Objective: To confirm if mirabegron 50�mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo. Methods: Post‐hoc analyses were carried out using pooled data from a Japanese phase�IIb and a phase�III study. The primary efficacy end‐point was baseline to end‐of‐treatment change in the mean number of micturitions/24�h. The secondary end‐points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24�h, and mean number of nocturia episodes/night. Other end‐points were quality of life and incontinence normalization rates. Results: Women with urgency urinary incontinence (placebo n =�204, mirabegron n�=�214) and mixed urinary incontinence (placebo n�=�122, mirabegron n�=�139) were included. Change in mean micturitions/24�h at end‐of‐treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end‐points, median changes for mirabegron were statistically significant versus placebo at end‐of‐treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population. Mirabegron showed larger improvements versus placebo in all quality‐of‐life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo. Conclusions: Mirabegron 50�mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.

Takahashi, S., et al. (2021). "A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer." International Journal of Clinical Oncology 26(10): 1977‐1985.
	BACKGROUND: Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. METHODS: This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. RESULTS: Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose‐dependent manner. The overall response rate was 27.8%. CONCLUSIONS: Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. CLINICAL TRIAL REGISTRATION NUMBER: JapicCTI‐163164.

Takahashi, Y., et al. (2022). "SINGLE-ARM CONFIRMATORY CLINICAL TRIAL OF PERIOPERATIVE MANAGEMENT TO PREVENT POSTOPERATIVE SYMPTOMATIC PULMONARY EMBOLISM FOR GYNECOLOGICAL CANCER PATIENTS WITH ASYMPTOMATIC VENOUS THROMBOSIS EMBOLISM PREOPERATIVELY (GOTIC-VTE TRIAL)." International Journal of Gynecological Cancer 32(Supplement 3): A213.
	Objectives There is no established optimal perioperative venous thrombosis embolism (VTE) prophylaxis for gynecological cancer patients with asymptomatic VTE preoperatively. The GOTIC-VTE trial was a prospective, multi-center, singlearm, confirmatory clinical trial to investigate the prevention of postoperative symptomatic pulmonary embolism (PE) onset by seamless anticoagulant therapy from the preoperative to 4 weeks after surgery instead of withholding intermittent pneumatic compression (IPC). Methods Anticoagulant therapy was started immediately after the diagnosis of asymptomatic VTE, administration of unfractionated heparin (UFH) was resumed within 12 hours after surgery, and anticoagulant therapy was continued for 28 days by combining UFH, low-molecular weight heparin and edoxaban. IPC was not used during the perioperative period. The primary outcome was the incidence of symptomatic PE during the 28 days after surgery, which was compared with historical controls who received short-term anticoagulant therapy. Results Between February 2018 and September 2020, 99 patients were enrolled and 82 were included in the full analysis set. There were 58 patients with ovarian cancer, 21 with endometrial cancer and 3 with cervical cancer. 47 patients had deep vein thrombosis (DVT) alone, 18 had PE alone and 17 had DVT and PE in combination at the time of registration. No symptomatic PE was observed during the 28 days after surgery. Two patients had bleeding events. The AEs of Grade3 were only 3 cases, increased ALT, AST and GGT, respectively. Conclusions The seamless anticoagulant therapy from the preoperative to postoperative 4 weeks for gynecological malignancies with asymptomatic VTE was effective in preventing the onset of postoperative symptomatic PE.

Takahashi, Y., et al. (2021). "Efficacy and toxicity of pegylated liposomal doxorubicin as therapy for recurrent ovarian cancer in relation to the number of previous chemotherapy regimens: Comparison with gemcitabine." The Journal of Obstetrics and Gynaecology Research 47(2): 551-559.
	AIM: Pegylated liposomal doxorubicin (PLD) is one of the second-line chemotherapy regimens for platinum-resistant recurrent ovarian cancer, but in clinical practice, it is also used for third or subsequent lines of chemotherapy. There is no report on the efficacy and toxicity of PLD in relation to the number of previous chemotherapy regimens. The purpose of this study was to clarify these points and compare with the results of gemcitabine (GEM) therapy we reported previously. METHODS: We retrospectively reviewed the medical records of patients with platinum-resistant recurrent ovarian cancer who underwent two or more cycles of PLD therapy between July 2009 and March 2017 at our institution. We used our reported data of GEM for comparison analysis. RESULTS: Seventy-eight patients were enrolled in this study. The overall response rate was 19.2% and the disease control rate (DCR) was 53.8%. The DCR with 1, 2, 3, and 4 or more previous regimens was 53.8%, 48.6%, 63.6% and 66.7%, respectively. Grade 3/4 neutropenia and anemia developed in 59.0% and 12.8%, respectively. Grade 2 or higher hand -foot syndrome, stomatitis, and liver dysfunction developed in 25.6%, 25.6% and 2.6%, respectively. When the number of previous regimens was 3 or higher, the DCR of PLD was significantly higher than that of GEM (64.7% vs 30.8%, P = 0.037). CONCLUSION: The DCR did not decrease with a greater number of previous regimens. When the number of previous regimens was 3 or higher, PLD therapy had a superior DCR to GEM therapy. Toxicity was tolerable in PLD therapy.

Taliento, C., et al. (2023). "Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49(12): 107250.
	Background: PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC.; Methods: We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer.; Results: This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days).; Conclusion: This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 Published by Elsevier Ltd.)

Tam, T., et al. (2021). "Methenamine hippurate with cranberry capsules versus cranberryalone for uti prevention in a short-term indwelling foley catheter population following urogynecologic surgery: a double-blind randomized controlled trial." Female Pelvic Medicine & Reconstructive Surgery 27(10 SUPPL 1): S7.
	Objective: Urinary tract infection (UTI) rates following pelvic reconstructive surgery are high, with increased occurrence in those requiring an indwelling catheter. To date, there is conflicting data on the efficacy of non‐antibiotic agents for UTI prevention. We sought to investigate the efficacy of methenamine hippurate (methenamine) with cranberry capsules compared to cranberry alone. Our study focused on UTI rates in patients requiring indwelling catheterization following prolapse surgery. Methods: We conducted an institutional review board‐approved, randomized double‐blinded placebo‐controlled trial. Eligible participants underwent pelvic reconstructive surgery, failed a post‐operative voiding trial, and were discharged with an indwelling catheter. Patients were randomized to receive cranberry capsules with methenamine or cranberry with placebo and were instructed to take the pills twice daily until catheter removal at 1‐week. Our primary outcome was number of subjects treated for UTI based on positive culture or clinical symptoms within 1‐week of surgery. Secondary outcomes included incidence of UTI within 6‐weeks of surgery, bacterial species and amount grown on culture, medication compliance, urine pH at 1 week, duration of catheter use, side effects, and patient satisfaction with their medications. Student‐t test and Chisquare tests were used to detect differences between groups. Logistic regression was used to estimate treatment effect on incidence of UTI. Based on a prior study, a sample size of 88 patients per arm was calculated using alpha = 0.05 and 80% power. Results: From June 2019 to February 2021, 146 patients were randomized. Three subjects withdrew and 143 (81%) were included in this preliminary analysis; 69 received cranberry with placebo and 74 received cranberry with methenamine. The average age was 60.1 (±13) years, and groups were overall similar. There was no difference in preoperative post‐void residual (PVR), type of surgery performed, or sling placement. Seventy‐three percent of patients had a UTI treated within 1 week of surgery, but this was not significantly different between the placebo (78.3%) and methenamine group (68.9%) (OR 1.62; 95% CI (0.76‐3.45); P = 0.208). However, in the 6 weeks following surgery, incidence of UTI was significantly higher in the placebo group (91.3% vs 73.0%; OR 3.89; 95% CI (1.46‐10.38); P = 0.007). Majority of cultures grew 105 CFU/ mL with similar bacterial species. However, there was a non‐significant trend toward higher Pseudomonal infections among the placebo group (25% vs 11.1%; P = 0.056). There were no differences in total days of catheter use (P = 0.474), postoperative complications, or urine pH (P = 0.238). Compliance and satisfaction were high among both groups with low side effects. Logistic regression revealed no significant confounding variables. Conclusions: Methenamine did not significantly reduce UTI rates among women with an indwelling catheter following pelvic reconstructive surgery at 1 week. However, at 6 weeks, subjects taking methenamine had significantly lower incidence of UTI. We believe this supports the addition of methenamine in this population. Further research of methenamine among patients with shorter duration of catheterization could show a greater benefit.

Tam, T. Y., et al. (2022). "Methenamine Hippurate With Cranberry Capsules Versus Cranberry Alone for Urinary Tract Infection Prevention in a Short-Term Indwelling Foley Catheter Population After Urogynecologic Surgery: A Double-Blinded Randomized Controlled Trial." Obstetrical and Gynecological Survey 77(7): 401-403.
	(Abstracted from Female Pelvic Med Reconstr Surg 2022;28:e55–e61) Urinary tract infections (UTIs) after pelvic reconstructive surgery (PRS) can result in high rates of readmission, morbidity, and mortality. The prevalence of UTI ranges from 10% to 76%, and postoperative urinary retention due to catheterization can occur in up to 43% in this population.

Tamara, E., et al. (2021). "A protocol for a systematic review of behaviour change techniques used in the context of stillbirth prevention."
	
Tamy, C., et al. (2021). "Effects of green tea on women with polycystic ovary syndrome: Systematic Review."
	
Tamy, C., et al. (2022). "Robotic assisted surgery vs Laparoscopy or laparotomy for myomectomy: Systematic review and meta-analysis."
	
Tamy, C., et al. (2022). "Anti-mullerian hormone levels after metformin treatment in pcos patients: a systematic review."
	
Tamy, C., et al. (2022). "Candidiasis and infertility: a systematic review."
	
Tan, D. S. P., et al. (2022). "A multicenter phase II randomized trial of durvalumab (D) versus physician's choice chemotherapy (PCC) in patients (pts) with recurrent ovarian clear cell adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3)." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: The optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. Prior data suggests rOCCC is a chemo-resistant disease that may respond to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibition (ICI). We aimed to determine the efficacy of D versus PCC in pts with rOCCC. Method(s): In this multicentre, openlabel, randomised phase 2 trial, 9 academic centres across Singapore, South Korea and Australia, enrolled rOCCC (determined histologically) and Eastern Cooperative Oncology Group performance status (PS) 0-2 pts, who had recurred after prior platinum-based chemotherapy and had not received more than 4 prior lines of systemic therapy, nor prior ICI therapy. Eligible pts were randomly assigned (2:1), using dynamic block randomization with block size of 6, and stratification by ECOG PS, to receive D (1500mg on day 1, in 28-day cycles) or PCC until disease progression (PD), intolerable toxicity or withdrawal of consent. Pts with PD on PCC were allowed to crossover to D. The primary endpoint was investigator-assessed progression-free survival (PFS) by RECIST version 1.1 and analyses included pts who had commenced at least 1 cycle of study treatment. Result(s): Between 7 Nov 2017 and 17 Feb 2020, 57 pts were assessed for eligibility, of whom 47 (PS 0-1) were randomly assigned to treatment with D (31 pts) or PCC (16 pts). At the data cut-off date (10 Jan 2022), the median follow-up was 83.0 weeks (IQR: 54.1-97.0) in the PCC group and 107.0 weeks (IQR: 82.7-116.4) in the D group. Median PFS was 7.4 weeks (IQR: 6.0-16.0) in the D group and 14.0 (IQR: 7.0-28.6) in the PCC group (HR 1.5 [95% CI 0.8-2.8], log-rank p = 0.89). The objective response rate (ORR) was 10.7% in pts randomised to D and 18.8% in the PCC group (p = 0.884). Clinical benefit rate (CR/PR/SD for >=16weeks) was similar for PCC (37.5%) and D (32.1%) (p = 0.756). 9 pts on PCC crossed over to receive D, with 2 of the 8 evaluable pts achieving partial response (PR). When crossover D pts were included, ORR to D was 13.9% (5/36) with a clinical benefit rate of 30.6% (11/36). Median duration of response was 44 weeks for the 3 PCC responders (PR to gemcitabine 24.9wks, PR to liposomal doxorubicin 65.7wks, CR to carboplatin/liposomal doxorubicin 44wks), and 18 weeks (range 2.1-45.3) for the 5 responders to D. Frequency of adverse events (AEs) across all grades was 68.8% for PCC and 38.7% for D. Grade 3/4 AEs were observed in 37.5% of PCC pts and 9.7% of D pts. Conclusion(s): No significant differences in PFS, ORR or clinical benefit rate were observed between D and PCC treatment in rOCCC. Treatment with D was associated with less grade 3-4 adverse events. Correlative translational analyses to elucidate predictive biomarkers of response and resistance are ongoing.

Tan, J., et al. (2023). "Meta-analysis of clinical efficacy of electroacupuncture versus conventional treatment for postoperative urinary retention in cervical cancer." Medicine 102(43): e35580.
	Background: To conduct a meta-analysis on the clinical efficacy of electroacupuncture in the treatment of postoperative urinary retention in cervical cancer, and to provide a theoretical basis for the promotion of electroacupuncture in the treatment of this disease.; Methods: Computer searches of the Cochrane library, Web of science, PubMed, Embase, Chinese Biomedical Literature Database, Wanfang database, Wipu database, and China National Knowledge Infrastructure Database database were conducted to find randomized controlled trials on electroacupuncture for postoperative urinary retention recovery in cervical cancer, all from the time of database creation to October 2022. Two evaluators independently evaluated the quality of the included literature and extracted the data. Data were combined and analyzed using RevMan 5.4.; Results: A total of 21 Randomized controlled trials with 1532 patients, 789 in the treatment group and 743 in the control group, were included. One descriptive analysis was performed and 20 Meta-analyses were performed. Meta-analysis results showed that: The electroacupuncture group was more effective than the control group in promoting recovery from urinary retention after cervical cancer, with a statistically significant difference [relative risk (RR)] = 1.32, 95% confidence interval (CI 1.26, 1.39), P < .00001; The duration of indwelling catheterization was reduced in the electroacupuncture group compared with the control group, with a statistically significant standard mean difference = -1.43, 95% CI (-1.62, -1.24), P < .00001; The healing rate in the electroacupuncture group was higher than that in the control group, with a statistically significant difference [RR] = 1.92, 95% CI (1.59, 2.30), P < .00001; The rate of urinary tract infection in the electroacupuncture group was lower than that in the control group, with a statistically significant difference [RR] = 0.22, 95% CI (0.10, 0.45), P < .00001. The incidence of urinary retention was lower in the electroacupuncture group than in the control group, and the difference was statistically significant [RR = 0.26, 95% CI (0.18, 0.39), P < .01].; Conclusion: Electroacupuncture can promote the recovery of urinary retention after cervical cancer surgery, and can improve the healing rate of patients after surgery, reduce the occurrence of urinary tract infection and shorten the duration of indwelling catheterization.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tan, J., et al. (2019). "The effect of unilateral tubal block diagnosed by hysterosalpingogram on clinical pregnancy rate in intrauterine insemination cycles: systematic review and meta-analysis." BJOG : an international journal of obstetrics and gynaecology 126(2): 227-235.
	Background: Fallopian tube occlusion is a common cause of infertility, but the effect of unilateral tubal block (UTB) on pregnancy rates (PR) after controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) remains controversial.; Objective: To evaluate PR after COH-IUI among infertile women with proximal and distal UTB diagnosed by hysterosalpingogram (HSG), compared against women with bilateral patent tubes experiencing unexplained infertility.; Search Strategy: We searched EMBASE, MEDLINE, Google Scholar, Cochrane Library, and PUBMED from inception to 14 January 2018.; Selection Criteria: Studies that report PR/cycle or cumulative PR among women with UTB and controls were included.; Data Collection and Analysis: Two authors independently selected and extracted study characteristics and data. Methodological quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.; Main Results: Among 2965 patients and 5749 IUI cycles across ten studies, no significant difference in PR/cycle (odds ratio, OR = 0.88; 95% confidence interval, 95% CI = 0.69-1.12) and cumulative PR (OR = 0.80, 95% CI = 0.62-1.04) was observed. Patients with proximal UTB demonstrated similar PR/cycle (OR = 1.06, 95% CI = 0.68-1.66) and cumulative PR (OR = 1.10, 95% CI = 0.75-1.62), compared with controls, whereas patients with distal UTB had significantly lower cumulative PR (OR = 0.49, 95% CI = 0.25-0.97, P = 0.04). Patients with proximal block also demonstrated significantly improved cumulative PR, compared with patients with distal block (OR=2.41, 95% CI = 1.37-4.25, P = 0.002).; Conclusion: Infertile patients with proximal UTB diagnosed by HSG can expect similar pregnancy rates after COH-IUI, compared with those with bilateral tubal patency and unexplained infertility, whereas patients with distal UTB have lower odds of pregnancy. These differences may reflect inherent diagnostic limitations of HSG or differences in underlying pathologies.; Tweetable Abstract: Meta-analysis evaluates pregnancy outcomes after COH-IUI in women with unilateral tubal block diagnosed by HSG. (© 2018 Royal College of Obstetricians and Gynaecologists.)

Tan, R., et al. (2022). "A retrospective study of focused ultrasound versus cryotherapy in treatment of cervical squamous intraepithelial lesions." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 39(1): 1294-1299.
	Purpose: To compare the efficacy and safety of focused ultrasound (FUS) therapy and cryotherapy for cervical squamous intraepithelial lesion (SIL).; Methods: In this retrospective study, data pertaining to women treated for cervical SIL with FUS therapy or cryotherapy at the Second Affiliated Hospital of Chongqing Medical University between 21 April 2018 and 31 August 2020 were obtained. The patients were followed up after 3-6 and 6-12 months. The proportions of women with no evidence of disease, recurrent disease, clearance of the human papillomavirus (HPV) and adverse effects or complications were determined.; Results: Of the 250 women with complete data who were included in the study, 144 and 106 received FUS therapy and cryotherapy, respectively. Overall, FUS therapy was observed to be more effective than cryotherapy (91.7 vs. 79.2%, p = 0.005). Statistically significant differences were noted in the treatment efficacy for patients with low-grade SIL (LSIL) (92.3 vs. 80.2%, p = 0.011). However, there were no significant differences in the treatment efficacy for patients with high-grade SIL (HSIL) (88.9 vs. 75.0%, p = 0.390). The recurrence rates in patients with LSIL treated with FUS therapy or cryotherapy showed no significant differences at the 6-12-month follow-up (1.0 vs. 6.0%, p = 0.163). Furthermore, there was no recurrence in patients with HSIL, either in the FUS or cryotherapy group. FUS therapy and cryotherapy resulted in similar HPV clearance at the 3-6-month follow-up (77.1 vs. 64.8%, p = 0.057). No statistically significant differences were observed in the complication rates between the two groups (3.5 vs. 1.9%, p = 0.717).; Conclusion: The results of this study suggest that FUS therapy is superior to cryotherapy in the treatment of cervical LSIL.

Tan, S., et al. (2021). "Licogliflozin versus placebo in women with polycystic ovary syndrome: A randomized, double-blind, phase 2 trial." Diabetes, Obesity & Metabolism 23(11): 2595-2599.
	Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. The dual sodium-glucose co-transporter 1/2 inhibitor (SGLT1/2i) licogliflozin (LIK066) ameliorates hyperinsulinism in patients with diabetes and obesity. This study examines the effect of licogliflozin on androgens in women with PCOS. In a multicentre, randomized, placebo-controlled, double-blind, 2-week trial, patients with PCOS received licogliflozin 50 mg or placebo three times a day (TID). Changes in free testosterone (FT), other androgens and variables of insulin resistance were analysed. Concentration of FT did not change (TRLIK066 :TRPCB [FT]: 0.88; 90% CI: 0.70-1.11; P = .353). Licogliflozin reduced androstendione (A4) by 19% (TRLIK066 :TRPCB [A4]: 0.81; 90% CI: 0.68-0.99; P = .089) and dehydroepiandrosteron sulphate (DHEAS) by 24% (TRLIK066 :TRPCB [DHEAS]: 0.76; 90% CI: 0.65-0.89; P = .008). Hyperinsulinaemia was reduced by 70% by licogliflozin (highest insulin concentration [MAXI]; TRLIK066 :TRPCB [MAXI]: 0·26; 90% CI:0.20-0.34; P < .001 and area under the curve insulin [AUCI]; TRLIK066 :TRPCB [AUCI]: 0.32; 90% CI: 0.25-0.41; P < .001). Diarrhoea and nausea occurred as common adverse events. Dual inhibition of SGLT1/2 ameliorates hyperinsulinaemia and hyperandrogenaemia in women with PCOS. Licogliflozin may represent a promising novel treatment option for PCOS.

Tan, X., et al. (2023). "Comparison of paclitaxel liposomes combined with carboplatin versus paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer." The Journal of International Medical Research 51(9): 3000605231200267.
	Objective: To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess their effects on serum human epididymis protein 4 (HE4), CA125, CA199, matrix metalloproteinase-2 (MMP2), MMP-7, and MMP-9 levels.; Methods: In this observational study, 102 patients with advanced ovarian cancer were assigned to receive paclitaxel liposomes combined with carboplatin (Group A) or paclitaxel combined with carboplatin (Group B). Clinical efficacy; serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels; and the occurrence of adverse reactions were compared between the groups.; Results: The overall response rate was significantly higher in Group A than in Group B. After chemotherapy, serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels were lower in Group A than in Group B. The incidence of myalgia, dyspnea, nausea and vomiting, facial flushing, peripheral neuropathy, and skin rash was lower in Group A than in Group B.; Conclusion: Paclitaxel liposomes combined with carboplatin displayed better efficacy in the treatment of advanced ovarian cancer than paclitaxel combined with carboplatin, which might be attributable to reductions in serum marker levels and the occurrence of adverse events.

Tanaka, T., et al. (2022). "Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan." International Journal of Clinical Oncology 27(6): 1084-1092.
	Background: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy.; Methods: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death.; Results: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively.; Conclusions: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients. (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Tandon, S. D., et al. (2021). "Comparing the effectiveness of home visiting paraprofessionals and mental health professionals delivering a postpartum depression preventive intervention: a cluster-randomized non-inferiority clinical trial." Archives of Women's Mental Health 24(4): 629-640.
	To determine whether pregnant women receiving the Mothers and Babies group-based intervention exhibited greater depressive symptom reductions and fewer new cases of major depression than women receiving usual community-based services, and to examine whether groups run by paraprofessional home visitors and mental health professionals yielded similar depressive symptom reductions and prevention of major depression. Using a cluster-randomized design, 37 home visiting programs were randomized to usual home visiting, Mothers and Babies delivered via home visiting paraprofessionals, or Mothers and Babies delivered via mental health professionals. Baseline assessments were conducted prenatally with follow-up extending to 24 weeks postpartum. Eligibility criteria were ≥ 16 years old, ≤ 33 gestation upon referral, and Spanish/English speaking. Depressive symptoms at 24 weeks postpartum was the primary outcome. Eight hundred seventy-four women were enrolled. Neither intervention arm was superior to usual care in decreasing depressive symptoms across the sample (p = 0.401 home visiting paraprofessional vs. control; p = 0.430 mental health professional vs. control). Post hoc analyses suggest a positive intervention effect for women exhibiting mild depressive symptoms at baseline. We have evidence of non-inferiority, as the model-estimated mean difference in depressive symptoms between intervention arms (0.01 points, 95% CI: -0.79, 0.78) did not surpass our pre-specified margin of non-inferiority of two points. Although we did not find statistically significant differences between intervention and control arms, non-inferiority analyses found paraprofessional home visitors generated similar reductions in depressive symptoms as mental health professionals. Additionally, Mothers and Babies appears to reduce depressive symptoms among women with mild depressive symptoms when delivered by mental health professionals. This trial is registered on ClinicalTrials.gov (initial post: December 1, 2016; identifier: NCT02979444).

Tandon, S. D., et al. (2022). "Results from an effectiveness-implementation evaluation of a postpartum depression prevention intervention delivered in home visiting programs." Journal of Affective Disorders 315: 113-120.
	Background: Building on growing research examining lay health professionals delivering postpartum depression preventive interventions, we conducted a hybrid effectiveness-implementation Type 2 trial to examine implementation metrics and determine whether pregnant women receiving Mothers and Babies 1-on-1 delivered by lay home visitors exhibit greater reductions in depressive symptoms and perceived stress than women receiving usual home visiting.; Methods: 1229 (672 control, 557 intervention) pregnant women were enrolled, with intervention participants receiving Mothers and Babies 1-on-1 delivered by a lay home visitor and control participants receiving usual home visiting services. Baseline and six-month follow-up assessments measured client mental health outcomes, with management information system data collected to assess intervention dosage. Surveys were administered nine months post-training to agency managers as well as home visitors who delivered any intervention content.; Results: Intent-to-treat analyses indicated a significant reduction in perceived stress among intervention participants compared to controls, while as-treated analyses showed significant reductions in perceived stress and depressive symptoms. Although all study sites adopted the intervention, <50 % of eligible women received the intervention. Over two-thirds of home visitors made at least one fidelity-consistent adaptation, with client recruitment and retention in home visiting highlighted as challenges to delivery.; Limitations: Unmeasured historical events may have affected study outcomes and caution should be used generalizing to perinatal women from different racial/ethnic groups and home visiting models.; Conclusion: Mothers and Babies 1-on-1 delivered by lay home visitors leads to reductions in perceived stress and depressive symptoms, suggesting task shifting to non-mental health professionals is viable when appropriate training and supervision is provided. (Copyright © 2022 Elsevier B.V. All rights reserved.)

Taneja, R., et al. (2023). "Diagnostic and therapeutic cystoscopy in bladder pain syndrome/interstitial cystitis: systematic review of literature and consensus on methodology." International Urogynecology Journal 34(6): 1165-1173.
	Introduction and Hypothesis: Cystoscopy has been routinely performed in patients suspected to be suffering from bladder pain syndrome/interstitial cystitis (BPS/IC) across the globe. The methodology reported by various guidelines appears to have differences in the techniques and hence there is a need for a review of all those techniques in order to arrive at a consensus. The aim was to review the literature describing the prevalent techniques of cystoscopy for patients of BPS/IC and try to evolve a consensus.; Methods: The group the Global Interstitial Cystitis, Bladder Pain Society (GIBS) has worked collectively to systematically review the literature using the key words, "Cystoscopy in Hunner's lesions, bladder pain syndrome, painful bladder syndrome and interstitial cystitis" in the PubMed, COCHRANE, and SCOPUS databases. A total of 3,857 abstracts were studied and 96 articles referring to some part of technique of cystoscopy were short-listed for review as full-length articles. Finally, six articles with a description of a technique of cystoscopy were included for final tabulation and comparison. The group went on to arrive at a consensus for a stepwise technique of diagnostic and therapeutic cystoscopy in cases of BPS/IC. This technique has been compared with the previously described techniques and may serve to be a useful practical guide for treating physicians.; Conclusion: It is important to have a uniform standardized technique for performing a diagnostic and therapeutic cystoscopy in patients with BPS/IC. Consensus on one such a technique has been arrived at and described in the present article. (© 2023. The International Urogynecological Association.)

Tang, J., et al. (2022). "Outcomes of laparoscopic radical hysterectomy in IA1- IB1 cervical cancer patients with low-risk: A multi-center retrospective study with 10 years' experience (487)." Gynecologic Oncology 166(Supplement 1): S241.
	Objectives: More evidence revealed that the oncological outcomes of open abdominal radical hysterectomy (OARH) were superior to those of laparoscopic radical hysterectomy (LRH) in patients with early-stage cervical cancer (CC). However, limited by the number of CC patients with IA and low-risk IB1, some aspects still needed more study to clarify. This retrospective study aimed to estimate the outcomes of LRH for IA1-IB1 cervical cancer patients with low- risk, which was defined as tumor <2cm, less than one-third stromal invasion, no lymphovascular space invasion (LVSI), no lymph node involvement. Method(s): By carefully studying the results of the Laparoscopic Approach to Cervical Cancer (LACC) Trial, we were surprised to find that the number of early-stage CC patients with low risk was relatively insufficient. Therefore, we retrospectively reviewed the medical records to identify the low-risk patients with FIGO 2018 stage IA1, IA2, and IB1 cervical cancer and who received laparoscopic or abdominal radical hysterectomy from January 2010 to December 2020 at four hospitals. The Mann-Whitney U test and the Chi-square test were used for the comparison of categorical variables. Progression-free survival and overall survival were compared between matched groups using Kaplan-Meier survival analysis and log-rank tests, along with univariable and multivariable regression analysis. Result(s): Of 5360 patients selected, 1850 (35%) met the inclusion criteria for this study from January 2010 to December 2020. Of these, 1090 patients underwent open surgery, and 760 patients had laparoscopic surgery. In the entire cohort, the two groups were similar in regard to clinical characteristics, such as age, body mass index (BMI), FIGO stage, histologic type and grade, pelvic lymph nodes, positive margins, stromal invasion, LVSI, and adjuvant therapy. LRH had better outcomes compared with OARH in terms of blood loss, transfusion rates, and the length of hospital stay. And in the subgroup analysis, when it referred to those patients with low-risk factors (tumor <2cm, superficial stromal invasion, negative LVSI, and no lymph node involvement), the LRH group was equivalent to the OARH group with respect to both disease-free survival (DFS) and 5-year overall survival (OS) rates. What's more, when the tumor was >2cm or accompanied by other medium and high-risk factors, the LRH group showed a significantly shorter DFS and OS than OARH, which was consistent with the LACC Trial. Conclusion(s): Among FIGO 2018 stage IA1-IB1 CC patients with low- risk, tumor <2cm, superficial stromal invasion, negative LVSI, and no lymph node involvement, there was no detrimental effect on survival between LRH and OARH. And it also needed more prospective studies to explore the oncological outcomes of low-risk CC patients with stage IA1-IB1. Besides, LRH was closely associated with worse oncological outcomes than OARH in patients with risk factors.Copyright © 2022 Elsevier Inc.

Tang, K., et al. (2021). "In vitro fertilization outcomes in women with polycystic ovary syndrome: A meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 259: 146-152.
	Objective: During the past three decades, applying IVF for infertility treatment PCOS women has increased significantly, and the landscape of treatment strategies has changed dramatically. However, early review of IVF on PCOS have insufficiently accounted for efficacy and safety of the technic. With abundant studies in recent years, there is a need to reconcile these new data.; Material and Methods: To compare reproductive and obstetric outcomes of IVF between women with and without PCOS, a meta-analysis of 95 studies involving more than 21289 PCOS patients and 43036 controls was performed.; Results: Despite longer stimulation duration (WMD = 0.34 day, 95 % CI: 0.09, 0.59) and lower dose of Gn required (WMD = -361.3 IU, 95 % CI: -442.3, -280.4), more oocytes (WMD = 3.67, 95 % CI: 3.14-4.21) and matured oocytes (WMD = 2.16, 95 % CI: 1.52-2.80) per cycle were obtained from PCOS women. There were no statistically significant differences for cleavage, high-grade embryo and implantation rate. Although similar pregnancy and live birth rates per cycle were achieved in PCOS and non-PCOS women after IVF, women with PCOS still suffered from significantly increased risks of miscarriage (OR = 1.44, 95 % CI: 1.20-1.72), biochemical pregnancy loss (OR = 1.89, 95 % CI: 1.48-2.41), and OHSS (OR = 3.58, 95 % CI: 2.86-4.48), in addition to lower fertilization rate (OR = 0.79, 95 % CI: 0.71-0.88). Adverse obstetric outcomes including ectopics pregnancy and multiple pregnancies are comparable between two groups. The overall cycle cancellation rate was significantly higher among PCOS women with OR of 2.55 (95 % CI: 1.67-3.89), and concern over OHSS or hyper-response constitute the main cause. Similar results were also observed after stratified analysis.; Conclusions: Our results support the effectiveness of IVF for infertility treatment among PCOS patients. However, options to minimize adverse outcomes regarding to lower fertilization, miscarriage, biochemical pregnancy loss and OHSS are required. Further studies elucidating detailed mechanism underlying these adverse outcomes could be of great importance to improve the experience of IVF treatment. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Tang, Q., et al. (2023). "Comparative Survival Outcomes of Hyperthermic Intraperitoneal Chemotherapy, Intraperitoneal Chemotherapy and Intravenous Chemotherapy for Primary Advanced Ovarian Cancer: A Network Meta-Analysis." Journal of Clinical Medicine 12(3).
	Objective: We aimed to compare the survival outcomes and adverse events of hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP)and intravenous chemotherapy (IP)for primary advanced ovarian cancer.; Methods: PubMed, CENTRAL (Cochrane Central Registry of Controlled Trials), Embase, Web of Science and Scopus were searched using multiple terms for primary advanced ovarian cancer, including randomized controlled trials and comparative studies in both Chinese and English (up to date 15 August 2022). Outcomes include overall survival, progression-free survival and adverse events. The data were pooled and reported as hazard ratio (HRs) with 95% confidence intervals. The Newcastle-Ottawa Scales were used to assess the risk of bias in the included comparative study. The Cochrane Collaboration's Risk of Bias Tool was used for randomized controlled trials.; Results: In total, 32 studies, including 6347 patients and 8 different platinum-based chemotherapy regimens, were included in this network meta-analysis. Our analysis results showed that HIPEC2 (carboplatin with area under the curve 10) exhibited a statistically significant OS benefit compared to IV, weekly dose-dense chemotherapy and HIPEC1 (cisplatin with 75/100 mg/m 2 ). Intraperitoneal plus intravenous chemotherapy was associated with a statistically significantly better likelihood of overall survival compared to IV. For progression-free survival, our statistical results only suggest a better progression-free survival in ovarian cancer patients treated with HIPEC1 compared with weekly dose-dense chemotherapy. No evidence of difference was observed between the other comparison groups. Compared with the non-HIPEC group, HIPEC may had a higher incidence of electrolyte disturbances (≥grade 3).; Conclusion: Our statistical analysis suggests that the groups receiving HIPEC2 had a better OS than the groups receiving IV, weekly dose-dense chemotherapy and HIPEC1. For PFS, our analysis only showed HIPEC1 is better than IV. Moreover, HIPEC may lead to a higher incidence of electrolyte disturbances (≥grade 3). HIPEC therapy for advanced ovarian cancer is currently controversial.

Tang, Q., et al. (2022). "Perioperative and Survival Outcomes of Robotic-Assisted Surgery, Comparison with Laparoscopy and Laparotomy, for Ovarian Cancer: A Network Meta-Analysis." Journal of oncology 2022: 2084774.
	Objective: We aimed to compare the perioperative and survival outcomes of robotic-assisted surgery, traditional laparoscopy, and laparotomy approaches in ovarian cancer.; Methods: PubMed, Cochrane Library, Embase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) were searched using multiple terms for ovarian cancer surgeries, including comparative studies in Chinese and English. Literatures are published before August 31, 2021. The outcomes include operating time, estimated blood loss, length of hospital stay, postoperative/intraoperative/total complications, pelvic/para-aortic/total lymph nodes, transfusion, and five-year overall survival rate. The dichotomous data, continuous data, and OS data were pooled and reported as relative risk, standardized mean differences, and hazard ratio HRs with 95% confidence intervals, respectively. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included studies.; Results: Thirty-eight studies, including 8,367 patients and three different surgical approaches (robotic-assisted laparoscopy surgery, traditional laparoscopy, or laparotomy approaches), were included in this network meta-analysis. Our analysis shows that the operating time of laparotomy was shorter than laparoscopy. The robotic-assisted laparoscopy has the least estimated blood loss during the surgery, followed by laparoscopy, and finally laparotomy. Compared with laparotomy, the incidence of blood transfusion was lower in the robotic-assisted laparoscopy and laparoscopy groups, and the length of hospital stay is shorter. Laparotomy had a significantly higher incidence of total complications than robotic-assisted laparoscopy and laparoscopy and higher postoperative complications than laparoscopy. For the number of pelvic/para-aortic/total lymph nodes removed by different surgical approaches, our analysis revealed no statistical difference. Our analysis also revealed no significant differences in intraoperative complications and 5-year OS among the three surgical approaches.; Conclusion: Compared with laparotomy, robotic-assisted laparoscopy and laparoscopy had a shorter hospital stay, decreased blood loss, fewer complications, and transfusion happened. The 5-year OS of ovarian cancer patients has no difference between robotic-assisted laparoscopy, laparoscopy, and laparotomy groups.; Competing Interests: The authors declare that they have no conflicts of interest and nothing to disclose. (Copyright © 2022 Qin Tang et al.)

Tang, R., et al. (2023). "Clinical evaluation of autologous platelet-rich plasma therapy for intrauterine adhesions: a systematic review and meta-analysis." Frontiers in Endocrinology 14: 1183209.
	Objective: This meta-analysis aims to evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) administration in reducing adhesion recurrence and improving pregnancy outcomes in patients with intrauterine adhesion (IUA).; Methods: We conducted a comprehensive search of Pubmed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) from inception to February 10, 2023, without any language or regional restrictions. We used random-effects models to assess odds ratios (OR) and weight mean differences (WMD) with 95% confidence intervals (CI).; Results: Our meta-analysis included a total of 730 patients from 10 clinical studies (6 RCTs and 4 non-RCTs). The results showed that PRP administration significantly increased endometrial thickness (WMD = 0.79, 95% CI: 0.40-1.19; P < 0.001; I 2 = 0.0%), menstrual volume (WMD = 2.96, 95% CI = 2.30-3.61; P < 0.001; I 2 = 0.0%), and days of menstruation (WMD = 1.13, 95% CI = 0.86-1.41; P < 0.001; I 2 = 0.0%). Additionally, the clinical pregnancy rate was also improved (OR = 1.82, 95% CI: 1.19-2.78; P = 0.006; I 2 = 0.0%). However, there was insufficient evidence to reach a conclusion regarding the effects of PRP on the recurrence rate of moderate to severe IUA, changes in AFS scores, miscarriage rate, and live birth rate.; Conclusions: Our analysis confirms that autologous PRP is an effective treatment for IUA. However, the limited sample size suggests that the results should be interpreted with caution. Therefore, larger and well-designed studies are necessary in the future to confirm these findings and explore the optimal PRP dosing regimens further.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023391115.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Tang, Xiao, He, Qiu, Zhang and Wang.)

Tang, R., et al. (2022). "The effects of cognitive behavioral therapy in women with polycystic ovary syndrome: A meta-analysis." Frontiers in psychology 13: 796594.
	Background: Cognitive behavioral therapy (CBT) has well-characterized benefits in alleviating diseases associated with depression, anxiety, and obesity, resulting in a marked improvement in the patient's quality of life. There are some studies regarding the effects of CBT on patients with polycystic ovary syndrome (PCOS). However, there is still no report of a meta-analysis for systematic assessment.; Objectives: This study aimed to evaluate the effectiveness of CBT in improving weight loss, anxiety, depression, life quality, compliance, and pregnancy outcomes in patients with PCOS.; Methods: Studies regarding CBT related to PCOS in PubMed, Cochrane library, Embase, ClinicalTrials.gov, CNKI, and WANFANG DATA were searched for up to 19 November 2020. A random-effects model was used to perform a meta-analysis.; Results: Eight trials regarding CBT compared with lifestyle modification and routine treatments were included. No differences in depression (SMD -1.11; 95% CI -2.28, 0.07; P > 0.05), body mass index (BMI) (SMD 0.88; 95% CI -0.94, 2.71; P > 0.05), or overall life quality (SMD 1.24; 95% CI -0.44, 2.92; P > 0.05) were evident between CBT and control groups; however, anxiety (SMD -1.12; 95% CI -2.1, -0.13; P < 0.05) and quality of life in hirsutism (SMD 0.92; 95% CI 0.48, 1.35; P < 0.05) were significantly improved. For secondary outcomes, both patient compliance and pregnancy rate were improved, but no significant change in pregnancy loss rate was identified.; Conclusion: CBT exhibited obvious advantages in the alleviation of anxiety, improvement of quality of life in hirsutism, and increase of compliance and pregnancy rate in patients with PCOS. Larger and higher-quality randomized controlled trials are needed to clarify the role of CBT in PCOS.; Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021225856].; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Tang, Yang, Yu and Fang.)

Tang, W., et al. (2022). "Safety and efficacy of thermal ablation for cervical metastatic lymph nodes in papillary thyroid carcinoma: A systematic review and meta-analysis." Frontiers in Endocrinology 13: 967044.
	Background: To evaluate the safety and efficacy of radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) for the treatment of cervical metastatic lymph nodes (CMLNs) of papillary thyroid carcinoma (PTC).; Methods: The Pubmed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies on the safety and efficacy of thermal ablations (RFA, MWA, and LA) for the treatment of CMLNs of PTC until March 30, 2022. A review of 334 potential papers identified 17 eligible papers including 312 patients. Fixed-effects model or random-effects model was used to evaluate the pooled proportions of volume reduction rate (VRR), complete disappearance, and recurrence, and pooled estimates of changes in the largest diameter, volume, and serum Tg after ablation. The pooled proportions of overall and major complications were calculated. Subgroup analysis based on treatment modalities. The heterogeneity among studies was analyzed by using Q statistics and inconsistency index I 2 . MINORS scale was used to evaluate the quality of the studies.; Results: 17 eligible studies were finally identified, including 312 patients and 559 CMLNs. The pooled proportions of VRR, complete disappearance and recurrence of CMLNs were 91.28% [95% confidence interval (CI) : 86.60-95.97%], 67.9% [95% CI : 53.1-81.1%] and 7.8% [95% CI : 3.0-14.1%], respectively. The pooled estimates of changes in the largest diameter, volume and serum Tg were 8.12 mm [95% CI : 6.78-9.46 mm], 338.75 mm 3 [95% CI : 206.85 -470.65 mm 3 ] and 5.96 ng/ml [95% CI : 3.68-8.24 ng/ml], respectively. The pooled proportions of overall and major complications were 2.9% [95% CI : 0.3-7.1%] and 0.3% [95% CI : 0-1.9%], respectively. Significant between-study heterogeneity was observed for complete disappearance ( P <0.01, I 2 = 88.6%), VRR ( P <0.001, I 2 = 99.9%), recurrence ( P =0.02, I 2 = 47.76%), overall complications ( P <0.02, I 2 = 44.8%), and changes in the largest diameter ( P < 0.001, I 2 = 82.6%), volume ( P <0.001, I 2 = 97.0%), and serum Tg ( P < 0.001, I 2 = 93.7%). Subgroup analysis showed heterogeneity of the VRR among the treatment modality ( I 2 range: 84.4-100%). The VRR of MWA was the highest (97.97%), followed by RFA (95.57%) and LA (84.46%) ( P < 0.001).; Conclusion: All thermal ablations were safe and effective for the treatment of CMLNs of PTC. However, each treatment had significant heterogeneity in VRR. Compared with RFA and MWA, LA was less effective in reducing the volume of CMLNs of PTC.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Tang, Tang, Jiang, Zhang, Wang, Niu, Zang, Zhang, Wang and Zhao.)

Tang, X., et al. (2020). "Chinese herbal compound prescription for Endometriosis: A protocol for systematic review and meta-analysis." Medicine 99(42): e22698.
	Background: Endometriosis (EMT) is one of the common diseases of women of childbearing age. EMT destroys the anatomical structure of the pelvis, which leads to abnormal ovulation and endocrine abnormalities. It also affects embryo implantation and makes patients infertile. Recently, it is confirmed that Chinese medicine also have an excellent clinical efficacy on EMT. Compared with the conventional western medicine treatment, it effectively relieve pain and other concomitant symptoms.; Methods and Analysis: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and CNKI.; Major Results: the overall effective rate, VAS score.; Secondary Outcomes: blood serum estradiol (E2), progesterone (P), Follicle-Stimulating Hormone (FSH), adverse events. Data will be collected independently by 2 researchers, and the risk of bias in meta-analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions". All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0.; Results: The curative effect and safety of Chinese herbal compound prescription treatment for EMT patients will be evaluated systematically.; Conclusion: The systematic review of this study will summarize the currently published evidence of Chinese herbal compound prescription treatment for EMT to further guide its promotion and application.; Ethics and Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER:: https://osf.io/p5nrk.

Tang, X., et al. (2021). "Kuntai Capsule Combined With Letrozole on Gonadal Hormone Levels and Ovarian Function in Patients With PCOS: A Systematic Review and Meta-Analysis." Frontiers in Endocrinology 12: 789909.
	Background: The efficacy of Kuntai capsule combined with letrozole (LE) in improving ovarian function of polycystic ovary syndrome (PCOS) has been evaluated before, but there is still a lack of evidence-based support for the regulation of sex hormone levels. In recent years, new randomized clinical trials (RCTs) have been reported on the effect of combined therapy on regulating sex hormone levels.; Objective: We aimed to systematically evaluate the efficacy of Kuntai capsule combined with LE in the treatment of PCOS.; Methods: A search across the China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang database, PubMed, Web of Science, The Cochrane Library, and Embase was conducted on Kuntai capsule combined with LE in the treatment of PCOS. The time of the self-built database was up to April 30, 2021. RCTs of LE in the control group and LE combined with Kuntai capsule in the experimental group were selected. RevMan5.3 software was used for data analysis.; Results: A total of 17 studies were gathered, which included 1,684 patients. The meta-analysis results showed that the total effective rate of the combined group was 93.36% and that of the LE group was 78.15%. The improvement in the ovulation rate, pregnancy rate, number of mature follicles, endometrial thickness, cervical mucus score, and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) in the combined group was consistent with the results of a previous meta-analysis and was better than that in the LE group ( p < 0.05). In addition, the combination group was better than the LE group in regulating the levels of estradiol (E2) and testosterone (T) ( p < 0.05). There were no adverse drug reactions in the two groups during treatment.; Conclusion: As a type of pure traditional Chinese medicine preparation, Kuntai capsule combined with LE had a better effect than LE alone in the treatment of PCOS, with advantages mainly reflected in enhancing ovarian function and regulating the levels of sex hormones in vivo , among others, but the value of combined therapy still needs to be verified by more high-quality RCTs.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Tang, Huang, Wang, Zhang, Dong and Yu.)

Tang, X., et al. (2020). "Dose-effect response in image-guided adaptive brachytherapy for cervical cancer: A systematic review and meta-regression analysis." Brachytherapy 19(4): 438-446.
	Purpose: This study aimed to integrate and update the dose-effect relationship between volumetric dose and local control for cervical cancer brachytherapy.; Methods and Materials: We identified studies that reported high-risk clinical target volume (HR-CTV) D 90 and local control probability by searching PubMed, Web of Science, and the Cochrane Library databases through Oct 27, 2019. The regression analyses were performed using a probit model between HR-CTV D 90 , D 100 , intermediate-risk clinical target volume (IR-CTV) D 90 , and dose to Point A vs. local control probability. Subgroup analyses were performed according to stratification: time of local control, income level of the country or region, stage of cancer, pathology, mean volume of HR-CTV, dose rate, image modality, concurrent chemoradiotherapy proportion, interstitial proportion, and mean overall treatment time.; Results: Thirty-three studies encompassing 2893 patients were included. The probit model showed a significant relationship between the HR-CTV D 90 value and the local control probability, p < 0.0001. The D 90 corresponding to a probability of 90% local control was 83.7 Gy EQD2,10 (80.6-87.8 Gy EQD2,10 ). Of the 33 studies included in our analysis, eight studies, including 1172 patients, reported the IR-CTV D 90 value, ranging from 59.1 Gy EQD2,10 to 72.3 Gy EQD2,10 . The probit model also showed a significant relationship between the IR-CTV D 90 value and the local control probability, p = 0.0464. The 60 Gy EQD2,10 for IR-CTV D 90 corresponded to an 86.1% local control probability (82.0%-89.8%).; Conclusions: A significant dependence of local control on HR-CTV D 90 and IR-CTV D 90 was found. A tumor control probability of >90% can be expected at doses >84 Gy EQD2,10 and 69 Gy EQD2,10 , respectively, based on an updated meta-regression analysis. (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Tang, Y., et al. (2022). "Retrospective Analysis of the Effect of Lidocaine Combined with Methylprednisolone on Pain Control After Uterine Artery Embolization." Frontiers in surgery 9: 875484.
	Background: The analgesic effect produced by the intra-arterial injection of lidocaine in patients undergoing uterine artery embolization has been proven to be safe and effective. Nevertheless, a significant degree of pain is typically experienced after the operation, and pain management is crucial. Methylprednisolone, which provides an anti-inflammatory effect, is widely used in the treatment of several diseases. To date, methylprednisolone has not been used after uterine artery embolization.; Methods: A total of 131 patients with uterine leiomyoma were retrospectively enrolled. Forty-five patients (control group) were treated with embolized microspheres for bilateral uterine artery embolization. Fifty (study group) and 36 (lidocaine group) patients were administered lidocaine mixed with embolized microspheres during embolization, and in addition, the study group was administered methylprednisolone. Completed pain scales at different time points during surgery were obtained from patients undergoing uterine artery embolization. Efficacy against pain was evaluated by comparing the pain score, inflammatory index, and use of sufentanil within 24 h followed by a Kruskal-Wallis Test and a least significant difference post-hoc analysis.; Results: The postoperative pain scores at 1, 4, and 7 h after uterine artery embolization in the study group (3.08 ± 2.09, 2.46 ± 1.93, and 2.38 ± 1.85, respectively) were significantly lower than those in the control group (4.84 ± 2.36, 4.16 ± 1.87, and 3.56 ± 1.93, respectively) and the lidocaine group (3.50 ± 2.10, 3.30 ± 1.88, and 3.28 ± 1.89, respectively). At the first 24 h after embolization, the total usage of sufentanil in the study group (31.4 ± 4.16) was significantly lower than those in the control group (45.7 ± 6.51) and the lidocaine group (38.3 ± 6.25). At 1 and 4 h, the pain scores of the lidocaine group were significantly lower than those of the control group. In addition, at the first 24 h after embolization, the total usage of sufentanil in the lidocaine group was significantly lower than that in the control group.; Conclusion: Lidocaine in combination with methylprednisolone can significantly alleviate pain and reduce the usage of sufentanil after bilateral uterine artery embolization. Thus, methylprednisolone is a recommended addition to the therapeutic regimen after embolization.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Tang, Lin, Zhang, Hu, Zhang, Wu, Zhou, Cai, Luo, Chi and Fang.)

Tang, Y., et al. (2023). "Bromocriptine inhibits proliferation in the endometrium from women with adenomyosis." Frontiers in Endocrinology 14: 1026168.
	Objective: Bromocriptine treatment has been shown to reduce menstrual bleeding and pain in women with adenomyosis in a pilot clinical trial. The underlying mechanism contributing to the treatment effect is however unknown. The purpose of this study was to explore the effect of bromocriptine on the proliferation and migration properties of the endometrium in women with adenomyosis, by assessing cellular and molecular changes after six months of vaginal bromocriptine treatment.; Methods: Endometrial specimens were collected during the proliferative phase from women with adenomyosis (n=6) before (baseline) and after six months of treatment with vaginal bromocriptine. Immunohistochemistry was used to determine changes in the protein expression of Ki67 in the endometrium of women with adenomyosis. Primary endometrial stromal cells isolated at baseline were expanded in vitro and exposed to different doses of bromocriptine to determine the optimal half-maximum inhibitory concentration (IC50) using CellTiter-Blue ® Cell Viability Assay. Cell proliferation was assessed by bromodeoxyuridine ELISA assay and Ki67 gene expression was checked by real-time PCR. The migratory ability of endometrial stromal cells was determined by wound healing and transwell migration assays. Small RNA sequencing was applied on tissues collected from women with adenomyosis before and after bromocriptine treatment to identify differentially expressed microRNAs (miRNAs) after bromocriptine treatment. Bioinformatic methods were used for target gene prediction and the identification of biological pathways by enrichment procedures.; Results: Vaginal bromocriptine treatment reduced the Ki67 protein expression in the endometrium of women with adenomyosis and did not change the prolactin mRNA expression and protein concentration of prolactin in endometrial tissues. Bromocriptine significantly inhibited the proliferative and migrative abilities of endometrial stromal cells derived from women with adenomyosis in vitro . Moreover, small RNA sequencing revealed 27 differentially expressed miRNAs between the endometrium of women with adenomyosis before and after six months of vaginal bromocriptine treatment. KEGG pathway analysis on targeted genes of 27 miRNAs showed that several signaling pathways associated with cell proliferation and apoptosis were enriched after bromocriptine treatment.; Conclusion: Bromocriptine treatment exhibits an anti-proliferative effect in the endometrium of women with adenomyosis in vivo and in vitro . Bromocriptine might inhibit the proliferation of endometrial tissue in adenomyosis in part through the regulation of dysregulated microRNAs and proliferation-associated signaling pathways.; Competing Interests: ES receives active research support regarding adenomyosis R01HD105714 from the Eunice Kennedy Shriver Institute of Child Health and Human Development of the National Institutes of Health, Bethesda, MD USA, and serves as an Associate Editor for Frontiers in Reproductive Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Tang, Ponandai-srinivasan, Frisendahl, Andersson, Pavone, Stewart, Lalitkumar, Korsching, Bogavarappu and Gemzell-Danielsson.)

Tang, Z., et al. (2023). "Quantitative risk-benefit profiles of oral contraceptives, insulin sensitizers and antiandrogens for women with polycystic ovary syndrome: A model-based meta-analysis." European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 190: 106577.
	Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic ovary syndrome (PCOS). However, unclear risk-benefit profiles jeopardize their appropriate clinical applications. This study aimed to quantitatively evaluate the effects of the aforementioned medications and to compare their risk-benefit profiles. Randomized controlled trials published until 14th March 2022 were searched in PubMed and Embase. A model-based meta-analysis was developed to examine the time-effect profiles of each medication. The maximal percentage change of the effect (E max ) and time to achieve half of E max (T 50 ) were estimated. Primary outcomes included menstruation, hirsutism score, free androgen index (FAI), body mass index (BMI), insulin sensitivity, and lipid profiles. Overall, 200 studies (9,685 patients and 385 arms) were identified for modeling. OCs performed exceptionally well in improving menstruation (E max : 149%; T 50 : 7.44 weeks), hirsutism score (E max : 66.2%; T 50 : 26.2 weeks), and FAI (E max : 75.7%; T 50 : 0.51 weeks). However, OCs elevated the triglyceride (TG) level (E max : 12.6%; T 50 :1.19 weeks). After 12-week OC treatment, the TG level of approximately 30% of patients, whose baselines were normal, exceeded the reference limit. This suggested that OC-induced dyslipidemia should be routinely monitored. The maximal BMI-lowering effect of metformin was similar to that of placebo (E max : 3.80%); however, metformin had a shorter T 50 (6.67 weeks versus 12.9 weeks). Further, active lifestyle intervention plus placebo significantly decreased BMI (E max : 8.78%). Adding metformin to active lifestyle intervention accelerated the BMI-lowering effect within 24 weeks, whereas with the extension of this addition beyond 24 weeks, BMI did not reduce further, which indicated that benefits were limited from this prolonged addition. AAs were less potent in reducing hirsutism score (E max : 40.2% versus 66.2%) and FAI (E max : 34.5% versus 75.7%) compared to OCs. OC plus metformin combined OC-derived androgen-suppressing effects and metformin-derived insulin-sensitizing effects, and partially relieved the OC-induced TG increase (E max : 9.76%). Baseline dependency was found in most clinical responses, implying that pharmacotherapies tailored based on baselines achieved more clinical improvements. This study presents new quantitative evidence on pharmacotherapies for PCOS. Currently, long-term risk-benefit profiles and emerging therapies are inadequately reported and require more further research.; Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest. (Copyright © 2023. Published by Elsevier B.V.)

Tangkananan, A., et al. (2022). "Impact of chemotherapy cycles on oncological outcomes in elders with locally advanced cervical cancer treated with concurrent chemoradiotherapy." Journal of Medical Imaging and Radiation Oncology 66(7): 1014-1021.
	Introduction: To investigate the association between chemotherapy (CMT) cycles and oncological outcomes in elders with locally advanced cervical cancer (LACC) who treated with concurrent chemoradiotherapy (CCRT).; Methods: We retrospective studied 498 elders with LACC who treated with radiotherapy (RT) or CCRT between 2002 and 2018. Patients were divided into three groups: RT, CCRT with 1-4 and CCRT with 5-6 cycles of CMT. We compared progression-free survival (PFS) and overall survival (OS) among the three groups and explored survival prognostic factors via multivariate analysis and time-varying analysis effect.; Results: There were 453 eligible patients; 222, 119 and 112 patients who received RT, CCRT with 1-4 and CCRT with 5-6 cycles of CMT, respectively. Patients in the RT group had older age, poorer performance status, more treatment with conventional RT technique and earlier treatment year comparing with both CCRT groups. Patients who received 5-6 cycles of CMT were less to have underweight, comorbidities and anaemia compared with the RT group. There were patients with lower FIGO stage in 5-6 cycles than in 1-4 cycles of CMT and RT groups. The 5-year PFS and OS between RT, CCRT with 1-4 and CCRT with 5-6 cycles of the CMT group were significantly different. Performance status, comorbidity, histology, FIGO stage and total received 5-6 CMT cycles were significant prognostic factors of PFS and OS. However, the benefits of receiving 5-6 CMT cycles were evidenced only within the first 2.5 years.; Conclusion: Elders with LACC who received 5-6 cycles of CMT concurrently with RT can improve PFS and OS, but the benefit persisted only within the first 2.5 years. (© 2022 Royal Australian and New Zealand College of Radiologists.)

Tani, T., et al. (2023). "Subclinical Cardiac Dysfunction in the Patients Treated With Anthracycline-Containing Chemotherapy in the Chronic Phase." Circulation 148(Supplement 1).
	Background: Anthracycline-induced cardiotoxicity is a concerning problem in the treatment of a variety of cancers. The highest incidence of anthracycline-induced cardiotoxicity was observed during the first year after the completion of chemotherapy, but the changes in cardiac function and biomarkers after the first year have not been adequately investigated. Method(s): We analyzed 105 consecutive patients who were followed up for 24 months after starting anthracycline-containing chemotherapy in our hospital from June 2018 to April 2021. Echocardiography and blood test for troponin I and B-type natriuretic peptide (BNP) were performed at baseline, 3 months, 6 months, 12 months, and 24 months after starting the chemotherapy. Result(s): The cancer types included 71 breast cancers, 18 hematologic cancers, 11 gynecologic cancers, and 5 soft tissue tumors. Compared to baseline, troponin I levels were increased at 3 months (0.011+/-0.007 ng/ml vs. 0.021+/-0.021 ng/ml, P<0.05) and 6 months (0.023+/-0.047 ng/ml, P<0.001), then, recovered to baseline levels. In contrast, BNP levels remained unchanged for 12 months but increased at 24 months compared to baseline (31.9 [5.8-625.7] pg/ml vs. 15.5 [5.8-89.2] pg/ml, P<0.01). In addition, the left ventricular ejection fraction was decreased from baseline to 6 months (65.4+/-4.8% vs. 63.6+/-4.5%, P<0.05) and 24 months (63.6+/-4.7%, P<0.05). Multivariate logistic analysis revealed that age (OR 1.049, 95% CI [1.006-1.097], P=0.029) and total anthracycline dose (OR 1.011, 95% CI [1.002-1.022], P=0.026) were predicting factors for elevated BNP levels above the normal range (>18.2 pg/ml) at 24 months. Conclusion(s): Subclinical cardiac dysfunction was developed after more than one year. Long-term followup is desirable to detect cardiac dysfunction in patients treated with anthracycline-containing chemotherapy.

Tanigawa, T., et al. (2022). "Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079)." Gynecologic Oncology 165(3): 413-419.
	Objective: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. Method(s): Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naive were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. Result(s): Sixty-nine patients were analyzed using our protocol. The median paclitaxel- carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8-88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3-17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1-11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. Conclusion(s): Paclitaxel-carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.Copyright © 2022 Elsevier Inc.

Tanmahasamut, P., et al. (2022). "Menopausal hormonal therapy in surgically menopausal women with underlying endometriosis." Climacteric : the journal of the International Menopause Society 25(4): 388-394.
	Objective: This study aimed to investigate the relationship between menopausal hormone therapy (MHT) and endometriosis recurrence in women who underwent hysterectomy with bilateral salpingo-oophorectomy to treat endometriosis.; Method: This retrospective cohort study included 330 women who underwent definitive surgery to treat endometriosis during 1996-2012. Follow-up data until December 2018 were analyzed. Patients were grouped as MHT non-users (non-MHT, n = 43), estrogen-only therapy (ET, n = 230), estrogen-progestogen therapy (EPT, n = 39) and tibolone ( n = 18).; Results: The mean age at surgery was 41.5 ± 5.3 years. The overall median follow-up duration was 6.0 years (interquartile range [IQR] : 3.0-10.4), and the median duration of MHT use was 66.0 months (IQR : 36.0-116.3). The overall recurrence rate was 3.0 % (95 % confidence interval : 1.5-5.5) and there was no significant difference in recurrence among the study groups. Disease recurrence resolved after MHT discontinuation, or change in MHT type and/or dose.; Conclusions: No significant association between MHT use and endometriosis recurrence was found in this study. The endometriosis recurrence rate was non-significantly different between ET and EPT. Recurrent endometriosis can be successfully treated without invasive measures. No study patients had malignant transformation after a median follow-up of 6 years. Our findings suggest that any of the three evaluated MHT regimens can be used in surgically menopausal Thai women with underlying endometriosis.

Tanoglu, F. B., et al. (2023). "Comparison of intraoperative and early postoperative results of patients undergoing laparoscopic versus laparotomic staging surgery for ovarian cancer." European Journal of Gynaecological Oncology 44(5): 125-131.
	Thus far, the traditional method of performing staging surgery in ovarian cancer has been laparotomy. Although randomized controlled trials are lacking, minimally invasive options are deemed safe and sufficient for staging and treatment of early-stage ovarian cancer. This study aims to compare the intraoperative and early postoperative outcomes of patients who underwent staging surgery via laparoscopy or laparotomy because of ovarian cancer. This retrospective study was conducted among 37 patients undergoing staging surgery done via laparoscopy (Group 1) or laparotomy (Group 2) between February 2018 and May 2022 at a single center. Intraoperative and early postoperative results were collected. Regarding postoperative complications between the two groups, the formation of lymphoceles and hernias in Group 2 was significantly higher compared to Group 1 (p = 0.019 and p = 0.050, respectively). When these groups were compared regarding Clavien-Dindo classification, Grade 1 complications were high among the laparoscopy group. In contrast, Grade 2, 3A and 3B complications were significantly higher in the laparotomy group (p = 0.002). Regarding hospital stay during the postoperative period, the patients in Group 2 stayed significantly longer compared to Group 1 (p = 0.001). As an alternative to open surgery for diagnosing and staging ovarian cancer, the laparoscopic approach is reliable and can be applied safely to patients. However, more prospective randomized studies are needed to support the obtained data.Copyright © 2023 The Author(s).

Tanos, V., et al. (2023). "Laparoscopic myomectomy complications: META analysis on RCTs and review of large cohort studies." European Journal of Obstetrics, Gynecology, and Reproductive Biology 287: 109-118.
	Complications of myomectomy are generally rare and highly dependent on the surgeons' skills and selection of patients. Haemorrhage, direct injury, post-operative pain and fever present as intra and peri-operative complications, while adhesions are considered late complications. 21 RCTs and 15 meta-analyses have been conducted to date, with the last comprehensive meta-analysis being published in 2009. The main disadvantage of the previous meta-analysis included incomplete selection of studies, inclusion of studies with small sample sizes, and major heterogeneity of methods used between studies. The aim of this meta-analysis comparing laparoscopic myomectomy (LMy) to open conservative myomectomy is to provide an updated review of the type, frequency and severity of complications. These results can direct teaching efforts and guidelines and give updated advice to gynaecologists. A literature search was conducted on PubMed and Google scholar for RCTs on this topic. 276 studies were identified and 19 RCTs ultimately met the criteria for inclusion in the meta-analysis and subsequent heterogeneity assessment. The results showed that laparoscopic myomectomy has a more favourable outcome with regards to several complications when compared with laparotomy. Laparoscopic myomectomy is significantly associated with lower Hg drop (WMD = -0.48, 95% CI [-0.89, -0.07], p = 0.02179); lower incidence of post-operative fever (RR = 0.43, 95% CI [0.29, 0.64], p < 0.001); lower levels of pain at 48Hrs post-op (WMD = -0.88, 95% CI [-1.63, -0.014], p = 0.02020) and decreased analgesia requests (RR = 0.49, 95% CI [0.37, 0.64], p < 0.0001). Prophylaxis use was associated with less adhesions (RR = 0.064, 95% CI [0.44, 0.92], p = 0.01), although not enough data was available to draw conclusions regarding specific prophylactic agents. No differences were found between LMy and laparotomy for blood loss (WMD = -13.6494, 95% CI [-44.48, 17.18], p = 0.38553) or pain at 24Hrs post-op (WMD = -0.19, 95% CI [-0.55, 0.18], p = 0.32136). These findings support previously published meta-analyses. Given the right indications of the surgery and training of the surgeon, LMy seems to be most preferable to laparotomy in achieving a better clinical result with fewer complications.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier B.V.)

Tanyi Janos, L., et al. (2023). "A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(2): 276-284.
	Purpose: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer.; Methods: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light.; Results: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported.; Conclusion: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

Tanyi, J. L., et al. (2021). "Phase 3, randomized, single-dose, open-label study to investigate the safety and efficacy of pafolacianine sodium injection (OTL38) for intraoperative imaging of folate receptor positive ovarian cancer." Journal of Clinical Oncology 39(15 SUPPL).
	Background: Pafolacianine sodium is under investigation as an adjunct to visual inspection and palpation by providing intra‐operative imaging of folate receptor positive (FR+) ovarian cancer. Since complete resection (R0) is the strongest predictor of overall survival, methods to enhance detection of lesions are expected to benefit patient outcomes. Methods: For this phase 3, randomized, multicenter, single dose, open‐label pivotal trial (NCT03180307), patients with ovarian cancer who were scheduled to undergo cytoreductive surgery were recruited from 11 sites in the US and Netherlands from March 2018 through April 2020. The study objectives were to confirm efficacy and safety of pafolacianine sodium (0.025 mg/kg i.v., ≥1 h prior to imaging) in combination with intraoperative near‐infrared fluorescence (NIRF) imaging to detect additional lesions not detected by palpation and normal white light alone. Results: Pafolacianine sodium was administered to 150 total patients (safety analysis set); 109 patients comprised the full analysis set for efficacy analyses. Patients had primarily serous adenocarcinoma (n = 72; 68.6%) and advanced stage disease (n = 83; 76.1%). In 33% of patients (36 of 109), NIRF imaging with pafolacianine sodium identified additional lesions that were not planned for resection and were not detected by normal white light and palpation (P < 0.001, 95% CI [0.243, 0.427]). Among patients who underwent interval debulking surgery, the rate was higher, at 39.7% of patients (23 of 58; 95% CI [0.270, 0.534]). At the individual lesion level, the accuracy of pafolacianine sodium with NIRF to detect ovarian cancer is reflected by sensitivity of 83% (95% CI [73.9, 89.4]) and a false positive rate of 32.7% (95% CI [25.6, 40.7]). Investigators reported achieving complete resection (R0) in 62.4% (68 of 109) of patients. Drug‐related adverse events (AEs) were reported by 30% of patients (45 out of 150). The most frequently reported drug‐related AEs were nausea (18.0%), vomiting (5.3%), and abdominal pain (4.7%). Infusion reactions at the time of the procedure were mostly (96%) mild or moderate in severity; 89% resolved within 24 hours of onset. No drugrelated serious AEs or deaths were reported. Conclusions: This phase 3 trial of pafolacianine sodium with NIRF imaging met its primary endpoint, intraoperatively identifying additional cancer not planned for resection in a statistically significant number of patients. Therefore, pafolacianine sodium may offer a novel realtime adjunct to current surgical imaging practice in ovarian cancer surgery.

Tao, L., et al. (2021). "Preventive effect of sodium hyaluronate gel combined with femmatone on intrauterine adhesion after high-risk induced abortion and its effect on serum IL-10 and IL-18 levels." 临床和实验医学杂志 20(1): 66‐70.
	Objective: To study the application effect of sodium hyaluronate gel and fenmoton in the prevention of intrauterine adhesions after high‐risk induced abortion and the effect of serum interleukin‐10 (IL‐10) and interleukin‐18 (IL‐18) level of influence. Methods: Using retrospective analysis method, the research objects were 180 high‐risk induced abortion patients admitted to Qinhuangdao Maternal and Child Health Hospital from October 2018 to October 2019. example. The control group was treated with motherwort alone, and the study group was additionally treated with sodium hyaluronate gel and fenmoton combined on the basis of the control group. The blood rheology indexes (plasma viscosity, whole blood viscosity), IL‐10 and IL‐18 levels before treatment and 3 months after treatment were compared with the incidence of intrauterine adhesion and the degree of adhesion (mild, moderate, severe) between the two groups. ) and the incidence of adverse reactions. Results: Before treatment, the levels of plasma viscosity, whole blood viscosity, IL‐10 and IL‐18 in the control group were (1.78±0.29) mPa·s, (6.75±2.16) mPa·s, (1008.37±193.19) ng/L, (175.78±29.46) ng/L, the study group were (1.81±0.32) mPa·s, (6.63±2.25) mPa·s, (1003.06±196.67) ng/L, (176.32±29.22) ng/L, respectively. After 3 months, the plasma viscosity, whole blood viscosity, IL‐10 and IL‐18 levels of the control group were (1.49±0.23) mPa·s, (5.67±1.39) mPa·s, (2647.63±521.54) ng/L, (130.09±18.31) ng/L, and the research group was (1.34±0.14) mPa·s, (3.58±1.21) mPa·s, (3102.54±583.28) ng/L, and (113.15±23.63) ng/L, respectively. Before treatment, there was no significant difference in plasma viscosity, whole blood viscosity, IL‐10 and IL‐18 levels between the two groups (P>0.05). Three months after treatment, the plasma viscosity, whole blood viscosity and IL‐18 levels of the two groups were lower than those before treatment, and the levels of IL‐10 were higher than those before treatment, and the differences were statistically significant (P<0.05). Conclusion: The application effect of sodium hyaluronate gel and fenmetone in the prevention of intrauterine adhesions after high‐risk induced abortion is significant, which can effectively reduce the degree and incidence of intrauterine adhesions, and can also improve hemorheology and serum leukocytes. hormone levels, and less adverse reactions.

Tao, T., et al. (2023). "Advances in autophagy modulation of natural products in cervical cancer." Journal of Ethnopharmacology 314: 116575.
	Ethnopharmacological Relevance: Natural products play a critical role in drug development and is emerging as a potential source of biologically active metabolites for therapeutic intervention, especially in cancer therapy. In recent years, there is increasing evidence that many natural products may modulate autophagy through various signaling pathways in cervical cancer. Understanding the mechanisms of these natural products helps to develop medications for cervical cancer treatments.; Aim of the Study: In recent years, there is increasing evidence that many natural products may modulate autophagy through various signaling pathways in cervical cancer. In this review, we briefly introduce autophagy and systematically describe several classes of natural products implicated in autophagy modulation in cervical cancer, hoping to provide valuable information for the development of cervical cancer treatments based on autophagy.; Materials and Methods: We searched for studies on natural products and autophagy in cervical cancer on the online database and summarized the relationship between natural products and autophagy modulation in cervical cancer.; Results: Autophagy is a lysosome-mediated catabolic process in eukaryotic cells that plays an important role in a variety of physiological and pathological processes, including cervical cancer. Abnormal expression of cellular autophagy and autophagy-related proteins has been implicated in cervical carcinogenesis, and human papillomavirus infection can affect autophagic activity. Flavonoids, alkaloids, polyphenols, terpenoids, quinones, and other compounds are important sources of natural products that act as anticancer agents. In cervical cancer, natural products exert the anticancer function mainly through the induction of protective autophagy.; Conclusions: The regulation of cervical cancer autophagy by natural products has significant advantages in inducing apoptosis, inhibiting proliferation, and reducing drug resistance in cervical cancer.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tao, W., et al. (2023). "Efficacy Analysis of Neoadjuvant versus Adjuvant Cisplatin-Paclitaxel Regimens for Initial Treatment of FIGO Stages IB3 and IIA2 Cervical Cancer." Medical science monitor : international medical journal of experimental and clinical research 29: e940545.
	BACKGROUND Large cancer lesions are often challenging to treat with surgical intervention alone. Neoadjuvant chemotherapy is frequently used for FIGO stage IB3 and IIA2 cervical cancers to optimize the outcomes of radical surgeries. This study aimed to compare the effectiveness of neoadjuvant chemotherapy, followed by adjuvant chemotherapy and radiotherapy, if necessary, with the traditional approach of adjuvant chemotherapy and radiotherapy after radical hysterectomy in treatment-naïve patients with cervical cancer of specified stages. MATERIAL AND METHODS A total of 245 female patients were administered either 70 to 85 mg/m² cisplatin and 165 to 175 mg/m² paclitaxel every 21 days (2 cycles) prior to radical hysterectomy, followed by adjuvant chemotherapy and radiotherapy if needed (neoadjuvant therapy, NT cohort, n=105), or received adjuvant chemotherapy and radiotherapy after radical hysterectomy adjuvant therapy, AT cohort, n=140). RESULTS In the NT cohort, 76% of patients responded to neoadjuvant chemotherapy, while 24% did not. Adverse operative, intraoperative, and postoperative outcomes were significantly more common among the non-responders (P<0.05). After 5 years, 91% of responders and 72% of non-responders survived without recurrence (P=0.0372), and 3% of responders and 28% of non-responders had died (P=0.0005). CONCLUSIONS The resistance to neoadjuvant chemotherapy is a poor prognostic factor. Neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant chemotherapy/radiotherapy appears to be advantageous for cervical cancer patients who respond well to neoadjuvant chemotherapy.

Tao, Y., et al. (2021). "[Biological mesh versus primary closure for pelvic floor reconstruction following extralevator abdominoperineal excision: a meta-analysis]." Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 24(10): 910-918.
	Objective: To compare the morbidity of perineum-related complication between biological mesh and primary closure in closing pelvic floor defects following extralevator abdominoperineal excision (ELAPE). Methods: A literature search was performed in PubMed, Embase, Cochrane Library, Web of Science, Wanfang database, Chinese National Knowledge Infrastructure, VIP database, and China Biological Medicine database for published clinical researches on perineum-related complications following ELAPE between January 2007 and August 2020. Literature inclusion criteria: (1) study subjects: patients undergoing ELAPE with rectal cancers confirmed by colonoscopy pathological biopsy or surgical pathology; (2) study types: randomized controlled studies or observational studies comparing the postoperative perineum-related complications between the two groups (primary perineal closure and reconstruction with a biological mesh) following ELAPE; (3) intervention measures: biological mesh reconstruction used as the treatment group, and primary closure used as the control group; (4) outcome measures: the included literatures should at least include one of the following postoperative perineal complications: overall perineal wound complications, perineal wound infection, perineal wound dehiscence, perineal hernia, chronic sinus, chronic perineal pain (postoperative 12-month), urinary dysfunction and sexual dysfunction. Literature exclusion criteria: (1) data published repeatedly; (2) study with incomplete or wrong original data and unable to obtain original data. Two reviewers independently performed screening, data extraction and assessment on the quality of included studies. Review Manager 5.3 software was used for meta-analysis. The mobidities of perineum-related complications, including overall perineal wound (infection, dehiscence, hernia, chronic sinus) and perineal chronic pain (postoperative 12-month), were compared between the two pelvic floor reconstruction methods. Finally, publication bias was assessed, and sensitivity analysis was used to evaluate the stability of the results. Results: A total of five studies, including two randomized controlled studies and three observational controlled studies, with 650 patients (399 cases in the biological mesh group and 251 cases in primary closure group) were finally included. Compared with primary closure, biological mesh reconstruction had significantly lower ratio of perineal hernia (RR=0.37, 95%CI: 0.21-0.64, P<0.001). No significant differences in ratios of overall perineal wound complication, perineal wound infection, perineal wound dehiscence, perineal chronic sinus and perineal chronic pain (postoperative 12-month) were found between the two groups (all P>0.05). Conclusion: Compared with primary closure, pelvic floor reconstruction following ELAPE with biological mesh has the advantage of a lower incidence of perineal hernia.

Taple Bayley, J., et al. (2020). "Enhancing behavioral treatment for women with pelvic floor disorders: Study protocol for a pilot randomized controlled trial." Contemporary clinical trials communications 17: 100514.
	Approximately one in four American women report bothersome urinary symptoms (e.g., urgency, frequency), which greatly impact quality of life, including mental health. Bidirectional relationships have been found between urinary symptoms and anxiety, such that urinary symptoms worsen emotional distress (i.e., anxiety and depression), and in turn anxiety can exacerbate these symptoms. Current methods to treat urinary symptoms, such as physical therapy and medications, do not address their emotional impact. As such, our multidisciplinary team is conducting a randomized control trial (RCT) of cognitive-behavior therapy (CBT) using the Unified Protocol (UP) versus supportive therapy in the context of integrated behavioral treatment in the urogynecology context. Women with bothersome urinary symptoms and anxiety are recruited from the Northwestern Medicine Integrated Pelvic Health Program (IPHP) -a transdisciplinary clinic including urogynecologists, urologists, colorectal surgeons, nurses, and physical therapists- and Northwestern Medicine Urology. Participants are randomized to one of two interventions: UP or supportive therapy. All participants attend therapy once per week for 12 weeks. Assessments of urinary symptoms, anxiety, and other indicators of psychological and physical functioning are completed at baseline, mid-treatment, post-treatment, and at 3- and 6-month follow-ups using patient-reported outcomes. The study has been preregistered on clinicaltrails.gov (ID: NCT03623880) and is currently ongoing. (© 2020 The Authors.)

Tara, D., et al. (2021). "Are psychological interventions effective in the management of outcomes for Chronic Pelvic Pain? A Systematic Review of Randomised Controlled Trials."
	
Taran Florin, A., et al. (2023). "Tumor-Free Resection Margin Distance in the Surgical Treatment of Node-Negative Squamous Cell Cancer of the Vulva Has No Impact on Survival: Analysis of a Large Patient Cohort in a Tertiary Care Center." Cancers 15(16).
	Background: The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone.; Methods: This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance.; Results: The patients were subclassified into three resection margin category groups: "1 to 3 mm" (n = 42), ">3 to 8 mm" (n = 47) or ">8 mm" (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62-0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71-0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) ( p = 0.300) or overall survival ( p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable.; Conclusion: The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival.

Tarek, E., et al. (2021). "The impact of high intensity focused ultrasound for treatment of uterine fibroids and adenomyosis on ovarian reserve."
	
Tariq, M., et al. (2022). "Evaluation of Dose Accumulation with Deformable Image Registration of External-Beam Radiotherapy and Brachytherapy for Cervical Cancer." Medical Physics 49(6): e200-e201.
	Purpose: The standard approach to evaluate cumulative dose to OARs and target coverage is DVH summation between EBRT and BT for cervical cancer. To consider anatomical and target volume changes of the cervical target, we compare with dose accumulation based on deformable image registration (DIR). Method(s): Five patients were studied who received 5040cGy (180cGyx28) of EBRT followed by three fractions (2100cGy total) of HDR using the Henschke applicator. Using Velocity (Varian Medical Systems, Palo Alto, CA), dose summation was applied with rigid registration of all three BT fractions onto the third BT fraction CT-SIM scan. The EBRT dose was deformed onto the third fraction BT scan and summed with the total BT dose. Total EBRT and BT dose was converted into EQD2 (Gy). Cumulative BT+EBRT DVH parameters based on DIR were compared with linear DVH summation and percent and absolute dose differences reported. The mean Jacobian determinant was reported for each patient to quantitatively assess DIR uncertainty. Result(s): Average percent differences of DVH summation and DIR-based dose accumulation were 0.77%, 1.26% and 1.90% for bladder, rectum and HR-CTV respectively. Average absolute dose differences were 1.26Gy, 1.52Gy and 2.16Gy for bladder, rectum and HR-CTV respectively. DVH summation overestimated D90% for HR-CTV for four out of five patients, five patients for rectum D2cc and four patients for bladder D2cc. For DIR uncertainty, the average Jacobian determinant was 0.71, 0.99 and 1.22 for the bladder, rectum and HR-CTV respectively. Conclusion(s): With DIR, absolute differences of OARs were up to 1Gy and 2Gy for HR-CTV. DVH summation is an accurate method of evaluating cumulative dose to OARs and target. We demonstrate the use of DIRbased dose accumulation from EBRT and BT. The importance of this method can be clinically utilized to modify fractional BT dose to account for anatomical and target volume changes.

Tariq, N., et al. (2021). "Impact Of Covid-19 On Post Natal Mental Health." Journal of Ayub Medical College, Abbottabad : JAMC 33(4): 659-663.
	BACKGROUND: In January, 2020 COVID-19 infection was declared a public health emergency characterized as pandemic by the World Health Organization (WHO). In March 2020, special guidelines were issued to address mental and psychological aspects of the disease survivors and community at large. This study was conducted with the aim to evaluate the psychological impact of COVID-19 on mothers in the postpartum period. METHODS: It was cross-sectional study of six months duration on COVID-19 positive deliveries and Covid negative mothers. A total of 84 women (42 Covid Positive and 42 Covid negative) were included through non-probability quota with consecutive sampling technique. Mothers with pre-existing mental health issues, those who had been on medication for any psychological issues or those who suffered from obstetrical and neonatal complications or required transfer to High Dependency Unit (HDU) were excluded from the study. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen the women for postpartum depression. Independent sample t test was used for continuous variables and Fisher exact test was used for qualitative variables. RESULTS: Mean EPDS score was 9.48±6.33 in COVID-19 positive group. The sub-scale analysis showed mean scores 1.6±1.76 and 4.86±2.94 for Anhedonia and Anxiety with statistically significant difference. CONCLUSIONS: Women experiencing COVID-19 infection during pregnancy were found to have greater anxiety and nervousness in post-natal period compared to their COVID-19 negative counterparts.

Tassinari, V., et al. (2023). "Endometriosis Treatment: Role of Natural Polyphenols as Anti-Inflammatory Agents." Nutrients 15(13).
	Endometriosis is an estrogen-dependent common chronic inflammatory disease defined by the presence of extrauterine endometrial tissue that promotes pelvic pain and fertility impairment. Its etiology is complex and multifactorial, and several not completely understood theories have been proposed to describe its pathogenesis. Indeed, this disease affects women's quality of life and their reproductive system. Conventional therapies for endometriosis treatment primarily focus on surgical resection, lowering systemic levels of estrogen, and treatment with non-steroidal anti-inflammatory drugs to counteract the inflammatory response. However, although these strategies have shown to be effective, they also show considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis; however, to date, only very limited literature is present on this topic. Polyphenols display important anti-endometriotic properties; in particular, they are potent phytoestrogens that in parallel modulates estrogen activity and exerts anti-inflammatory activity. The aim of this review is to provide an overview on anti-inflammatory activity of polyphenols in the treatment of endometriosis.

Tatar, S. A., et al. (2023). "Barbed versus conventional suture in laparoscopic myomectomy: A randomized controlled study." Turkish Journal of Obstetrics and Gynecology 20(2): 126-130.
	Objective: To compare the surgical and clinical results of traditional absorbable polyglactin 910 and barbed sutures in laparoscopic myomectomy. Material(s) and Method(s): This single-center randomized study included 75 women who underwent laparoscopic myomectomy. The uterine wall defects were closed with a continuous conventional absorbable polyglactin 910 suture (Vicryl; Ethicon, Somerville, NJ, USA) in 41 women and with a unidirectional barbed suture (V-Loc 180; Covidien, Mansfield, MA, USA) in 34 women. Result(s): The time required to suture the uterine wall defect was lower in the V-Loc group than in the Vicryl group (p=0.007). However, no significant difference was observed in the operative time between the two study groups. The intraoperative blood loss and need for postoperative blood transfusion were significantly lower in the barbed group than in the Vicryl group (p=0.018 and p=0.048, respectively). Conclusion(s): In laparoscopic myomectomy cases, the unidirectional barbed suture is more effective than the conventional absorbable suture. Barbed sutures facilitate the suturing process and reduce the time required to suture the uterine wall defect, blood loss, and the need for postoperative blood transfusion.Copyright © 2023 by Turkish Society of Obstetrics and Gynecology.

Tatarchuk, T. F., et al. (2023). "VITAMIN D SUPPLEMENTATION IN BACTERIAL VAGINOSIS." Reproductive Endocrinology 68: 36-42.
	Research objectives: to evaluate the effect of vitamin D supplementation (Olidetrim) in the complex anti-relapse therapy of bacterial vaginosis (BV) in women of reproductive age. Materials and methods. The study included 63 women of reproductive age with BV and with a level of 25-hydroxyvitamin D below 75 nmol/l, who were divided into groups: the main group included 32 women who were prescribed standard therapy (metronidazole 500 mg twice a day for 7 days) and cholecalciferol (Olidetrim) 4000 IU/day with subsequent continuation of its intake in a dose 2000 IU/day for up to 6 months; the comparison group included 31 women, who were not intake vitamin D preparation during the standard therapy and during the next 6 months of observation. After treatment, women provided completed questionnaires and self-collected vaginal swabs 1, 3, and 6 months after beginning of the study or before BV relapse. Evaluation of Gram-stained smears was carried out by microscopy according to Hay/Ison criteria, where BV corresponded to type III. The level of 25-hydroxyvitamin D in blood serum was determined by the chemiluminescent immunoassay method before the start of the study and at 3 and 6 months of follow-up. The primary endpoint was BV recurrence at any post-treatment interval; the patients were offered a second treatment in this case. Results. Vitamin D deficiency at the beginning of the study was detected in 12 (37.5%) patients of the main group and in 13 (41.94%) women of the comparison group, an insufficient level - in 20 (62.5%) patients of the main group and in 58.06% women of the comparison group. Patients complained of pathological vaginal discharge, itching, burning and dyspareunia lasting from 1 week to 2 months. At the seven-day course of basic BV therapy all participants noted the normalization of discharge and the absence of vaginal discomfort. Positive dynamics were also observed according to the gynecological examination. One month after the treatment, 4 (12.5%) participants of the main and 6 (19.36%) women of the comparison group noted the recovery of symptoms. Absence of BV recurrence after 3 months was noted by 25 (78.12%) women of the main group and 16 (51.61%) women of the comparison group (p = 0.054), that was confirmed by the laboratory tests. At the same time, the level of 25-hydroxyvitamin D in the main group increased by 43.37% (p = 0.05), and in the comparison group it did not differ from the initial level. There were no complaints in 24 (75.0%) patients after 6 months, however, a laboratory-confirmed normal state of the vaginal microbiome was observed in 22 (70.96%) participants of the main group and in 14 (45.16%, p = 0.07) women of the comparison group. Continuation of vitamin D intake at a dose of 2000 IU/day for the next 3 months demonstrated maintenance of the 25-hydroxyvitamin D level within normal values (81.7 +/- 6.23 nmol/l in the main group vs. 38.51 +/- 5.43 nmol/l in comparison group, p = 0.05). Conclusions. A decrease in the frequency of BV recurrences in women during support a normal level of vitamin D was found, which allows recommending the inclusion of cholecalciferol supplementation (Olidetrim) in the standard treatment. In patients with recurrent BV a long-term monitoring of the serum level of vitamin D is advisable in order to timely prescribe supplementation.Copyright © 2023 Trylyst. All rights reserved.

Tate, S., et al. (2021). "Tailored-dose chemotherapy with gemcitabine and irinotecan in patients with platinum-refractory/resistant ovarian or primary peritoneal cancer: a phase II trial." Journal of Gynecologic Oncology 32(1): e8.
	OBJECTIVE: We investigated the efficacy and toxicity of tailored-dose chemotherapy with gemcitabine and irinotecan for platinum-refractory/resistant ovarian or primary peritoneal cancer. METHODS: We enrolled patients with ovarian or primary peritoneal cancer who received ≥2 previous chemotherapeutic regimens but developed progressive disease during platinum-based chemotherapy or within 6 months post-treatment. All patients received gemcitabine (500 mg/m²) and irinotecan (50 mg/m²) on days 1 and 8 every 21 days at the starting dose. The dose was increased or decreased by 4 levels in subsequent cycles based on hematological or non-hematological toxicities observed. The primary endpoint was progression-free survival (PFS), and secondary endpoints were disease control rate (DCR), overall survival (OS), and adverse events. RESULTS: We investigated 25 patients who received 267 cycles (median 8 cycles/patient) between October 2008 and May 2011. Tailored-dose gemcitabine was administered up to the 5th cycle as follows: 1,000 mg/m² in 1 (4%), 750 mg/m² in 16 (64%), 500 mg/m² in 6 (24%), and 250 mg/m² in 2 patients (8%). The median PFS and OS were 6.2 months (95% confidence interval [CI]=2.7-10.7) and 16.8 months (95% CI=9.4-30.7), respectively. The DCR was 76%, and PFS was >6 months in 12 of 25 patients (48%). Grade 3 hematological toxicities included leukopenia (9.4%), neutropenia (11.2%), anemia (9.8%), and thrombocytopenia (1.1%). Grade 3/4 non-hematological toxicities did not occur except for fatigue in one patient. CONCLUSIONS: Tailored-dose chemotherapy with gemcitabine and irinotecan was effective and well tolerated in patients with platinum-refractory/resistant ovarian or primary peritoneal cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN000004449.

Tate, S., et al. (2022). "Bevacizumab-based Salvage Chemotherapy Improves Survival Outcomes for Patients With Brain Metastasis from Ovarian Cancer." Anticancer Research 42(5): 2637-2644.
	Background/aim: Brain metastases from ovarian cancer remain rare and the appropriate treatment is unknown. We investigated survival outcomes following salvage chemotherapy before and after bevacizumab approval to evaluate the efficacy of bevacizumab in patients with brain metastasis from ovarian cancer.; Patients and Methods: We investigated 23 consecutive patients with brain metastasis from ovarian cancer at our hospital between 2001 and 2020. Bevacizumab was administered for treating ovarian cancer after approval in Japan in November 2013. Survival after brain metastasis was compared between 9 patients treated before bevacizumab approval (2000-2013) and 14 patients treated after approval (2014-2020). Seven patients treated in the latter period received bevacizumab-salvage chemotherapy for brain metastasis.; Results: Median survival in all patients was 9.1 months [95% confidence interval (CI)=4.2-33.5]. In addition, patients treated during the latter period presented better survival outcomes than those treated in the former period (former, 2.9 months vs latter, 33.5 months, log-rank test, p=0.015; Wilcoxon test, p=0.009). Multivariate analysis revealed that bevacizumab addition (p=0.020), interval to brain metastasis (p=0.005), number of brain lesions (p=0.001), number of recurrences (p=0.001), and platinum sensitivity (p=0.028) were independently associated with survival in all cohorts.; Conclusion: Bevacizumab-based salvage chemotherapy may improve survival outcomes in patients with brain metastasis. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Tate, S., et al. (2022). "Highly Aggressive Surgery Benefits in Patients With Advanced Ovarian Cancer." Anticancer Research 42(7): 3707-3716.
	Background/aim: We investigated whether highly aggressive surgery has survival and perioperative complication benefit in patients with advanced ovarian cancer.; Patients and Methods: This retrospective study included 209 patients with stage III/IV ovarian cancer who underwent aggressive surgery [surgical complexity score (SCS) ≥8] between January 2008 and December 2018. Patients were categorized into the SCS 8-12 (less aggressive surgery, 83 patients) and SCS ≥13 (highly aggressive surgery, 126 patients) groups. Survival outcomes and perioperative complications between the groups were compared. Patient suitability for primary debulking surgery or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) was based on the evaluation of performance status, tumor load, and ascites. If patients were suitable for NACT/IDS, the residual tumor margins were marked at the initial laparotomy. The previously marked lesions were removed during IDS, even in patients with macroscopic tumor resolution.; Results: Prevalence rates of stage IV disease, poor performance status, presence of omental cake, peritoneal cancer index ≥15, and IDS performed were significantly higher in the highly aggressive surgery group than in the less aggressive surgery group. The median progression-free survival (PFS) and overall survival (OS) were not significantly different between the groups (PFS, 32 and 31 months, respectively; p=0.622; OS, 99 and 75 months, respectively; p=0.390). The incidence of severe perioperative complications was not significantly different between the less aggressive group (4.8%) and the highly aggressive surgery group (6.4%) (p=0.767).; Conclusion: Highly aggressive surgery with appropriate selection regardless of the timing of cytoreduction benefits patients with advanced ovarian cancer. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Tatiana, A., et al. (2021). "The efficacy of mindfulness-based interventions on physiological and psychological outcomes in women with Polycystic Ovary Syndrome: A systematic review."
	
Tatsuki, S., et al. (2022). "Efficacy and Safety of Platinum Rechallenge in Patients With Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer: A Multicenter Retrospective Study." Anticancer Research 42(9): 4603-4610.
	Background/aim: Ovarian cancer diagnosed with platinum-resistant recurrence has very poor prognosis and single-agent chemotherapy with no cross-resistance to prior chemotherapy is recommended for its treatment. In this study, we retrospectively evaluated the efficacy and safety of platinum rechallenge therapy for once diagnosed with platinum-resistant ovarian cancer who had a platinum-free interval (PFI) of at least 6 months.; Patients and Methods: The study included 49 patients who received platinum rechallenge therapy for ovarian, fallopian tube or primary peritoneal cancer who were once diagnosed with platinum-resistant recurrence between January 2010 and March 2021 and evaluated the efficacy and safety of this treatment. In addition, patient background factors were identified, and independent prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated.; Results: A complete response was noted in 7 cases, partial response in 21, stable disease in 9, and progressive disease in 10. The response and disease control rates were 55% and 76%, respectively. The median PFS and OS were 8.5 months and 35.8 months, respectively. The independent prognostic factor was PFI for OS, and there was no independent prognostic factor for PFS. Seven patients discontinued chemotherapy owing to serious adverse events, including one patient with treatment-related death.; Conclusion: Platinum rechallenge therapy for patients with platinum-resistant recurrence did not cause previously unreported adverse events, and the adverse events were manageable. In addition, high response and disease control rates were observed, as well as long-term OS. Platinum rechallenge therapy for platinum-resistant ovarian cancer may be a viable treatment option. (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Tauseef, A., et al. (2023). "Bevacizumab combined with platinum-based chemotherapy in primary or relapsed ovarian cancer patients: Meta-analysis and literature to review." Journal of family medicine and primary care 12(11): 2797-2804.
	Introduction: Earlier, patients with advanced ovarian cancer were treated with a combination of cytoreductive surgery and platinum-based chemotherapy, which had significant outcomes in the past until an increase in relapse and resistance to treatment, which led to the use or development of bevacizumab (a vascular endothelial growth factor inhibitor) in the treatment of primary or relapsed ovarian cancer.; Method and Methodology: This study includes five-phase three randomized controlled clinical trials designed to study the impact of bevacizumab in combination with platinum-based chemotherapy compared with platinum-based chemotherapy alone.; Results: This study demonstrated significant improvement in the progression-free span but no improvement in overall survival in the treatment group when compared with the control group. Also, adverse effects reported with combination therapy were tolerable and easily manageable by decreasing the infusion rate or by decreasing the frequency of infusion.; Competing Interests: There were no financial or nonfinancial conflicts noticed or witnessed among all the authors of the submitted projects. (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Tavira, B., et al. (2024). "Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/ MINOVA Study)." Clinical Cancer Research 30(1): 176-186.
	Purpose: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. Experimental Design: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. Result(s): Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4 T cells, an increase of CD8 T cells, and an upregulation in effector/regulatory cell ratio (CD8/CD4FOXP3). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS). Conclusion(s): The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4, CD8 lymphocyte populations, and CD8/CD4FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer.Copyright ©2023 The Authors; Published by the American Association for Cancer Research.

Tay, F., et al. (2023). "Efficacy and Safety of Combined Chemotherapy Regimens with Bevacizumab in Platinum-sensitive Ovarian Cancers." Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 33(9): 1006-1011.
	Objective: To determine the differences in terms of overall survival in platinum-sensitive ovarian cancer (PSOC) patients undergoing various chemotherapy protocols, and to demonstrate patient tolerance, toxicity, and efficacy data with the use of bevacizumab in different protocols.; Study Design: An observational study. Place and Duration of the Study: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from January 2018 to January 2022.; Methodology: Patients aged 18 and above, who had received treatment for PSOC, were included in the study. Patients with platinum-resistant disease and those for whom bevacizumab usage was contraindicated were not enrolled in the study.; Results: For the 95 patients, the median age was 55 (34-78) years. Median follow-up are 39.7 (39.2-47.5) months. Median progression-free survival (PFS) of the patients are 10.8 (7.3-14.0) months for carboplatin-gemcitabine-bevacizumab (CGB), 10.9 (IQR 5.5-14.3) months in the carboplatin-liposomal doxorubicin-bevacizumab (CLdB) arms, and 6.1 (IQR 5.8-14.3) months in the carboplatin-paclitaxel-bevacizumab (CPB) group (p=0.79). The median overall survivals (OS) are 37.9 (IQR 33.3-46.9) months in the CGB arm, 41.0 (IQR 38.0-50.3) months CPB arm, and 41.3 (IQR 38.1-52.3) months in the CLdB arm (p=0.173).; Conclusion: There was no difference in terms of overall survival among all three chemotherapy protocols. However, due to the difference in toxicity, the treatment should be selected on a patient-specific basis. Additionally, the use of bevacizumab at a dose of 7.5 mg/kg was demonstrated to be equivalent to using 15 mg/kg in terms of overall survival. This lower dose is also important to avoid financial toxicity.; Key Words: Bevacizumab, Ovarian cancer, Platinum-based chemotherapy, Tolerability, Adverse clinical events.

Taylor, H., et al. (2021). "Long term secondary efficacy of linzagolix for heavy menstrual bleeding (HMB) due to uterine fibroids (UF): 52-week results from two placebo-controlled, randomized, phase 3 trials." Human reproduction (Oxford, England) 36(SUPPL 1): i59.
	Study question: Are symptomatic improvements in women with UF observed after 24 weeks of linzagolix treatment with or without add‐back therapy (ABT) maintained over 52 weeks? Summary answer: Improvements in anemia, pain and quality of life previously reported at 24 weeks were maintained at 52 weeks. What is known already: We previously reported that partial or full suppression of estradiol (E2) with once daily doses of either 100 or 200 mg linzagolix for 24 weeks, with or without ABT, were effective in reducing heavy menstrual bleeding associated with uterine fibroids, improving other symptoms such as pain and anemia and improving quality of life. Here we report the maintenance of effect on secondary endpoints after 52 weeks of treatment. Study design, size, duration: Linzagolix is an investigational, oral GnRH antagonist being developed to treat HMB due to UF. PRIMROSE 1 (P1, USA, NCT03070899) and PRIMROSE 2 (P2, Europe and USA, NCT03070951) are randomized, double‐blind, placebo‐controlled Phase 3 trials, with essentially identical design, investigating the efficacy and safety of linzagolix with and without hormonal add‐back therapy (ABT: 1 mg estradiol/0.5 mg norethindrone acetate) once daily for 52 weeks. Participants/materials, setting, methods: Participants had HMB due to UF (>80mL menstrual blood loss (MBL)/cycle) and were equally randomized to: placebo, linzagolix 100mg, linzagolix 100mg+ABT, linzagolix 200mg, or linzagolix 200mg+ABT. After 24 weeks, subjects originally randomized to placebo or linzagolix 200mg were switched to linzagolix 200mg+ABT except in P1 where 50% placebo subjects continued placebo until 52 weeks. Secondary efficacy assessments included hemoglobin, pain (0‐10 numeric rating scale) and health related quality of life (HRQL) on the UF‐QoL questionnaire. Main results and the role of chance: P1 trial subjects (n=526) had a mean age of 42 years, pain score of 6.6 and HRQL total score (0‐100) of 36.4 and 63% were Black. P2 trial subjects (n=511) had a mean age of 43 years, pain score 4.8 and HRQL total score of 46.1 and 5% were Black. Mean baseline MBL was about 200 mL per cycle in both studies. In both trials, significant improvements compared to placebo observed at week 24 for secondary endpoints, including pain, anemia and QoL in all linzagolix treatment groups were maintained at 52 weeks. Mean±SD hemoglobin levels in anemic patients (<12 g/dL) increased from baseline by 1.7±1.9, 1.9±1.7, 2.2±2.4, 2.7±1.9 in P1 and 1.2±1.9, 2.9±1.8, 2.4±2.1, 3.0±1.4 in P2 in the 100mg, 100mg+ABT, 200mg/200mg+ABT, 200mg+ABT groups, respectively, compared to 0.6±1.8 with placebo (P1). Mean±SD change from baseline in pain scores were ‐3.3±3.1, ‐2.7±3.2, ‐2.6±3.0, ‐3.9±3.2 in P1 and ‐2.6±3.1, ‐2.6±2.8, ‐3.0±2.6, ‐2.8±3.0 in P2 in the 100mg, 100mg+ABT, 200mg/200mg+ABT, 200mg+ABT groups, respectively, compared to ‐0.4±2.5 with placebo (P1). Mean±SD change in HRQL total scores were 25.0±26.2, 34.2±30.1, 29.7±29.2, 38.3±29.2 in P1 and 16.8±24.0, 29.6±23.2, 31.9±26.8, 30.7±26.0 in P2 in the 100mg, 100mg+ABT, 200mg/200mg+ABT, 200mg+ABT groups, respectively, compared to 14.6±23.9 with placebo (P1). Limitations, reasons for caution: Here we report data in both trials up to 52 weeks of treatment. No statistical comparisons were done at 52 weeks (the primary analysis was done after 24 weeks treatment). Post‐treatment follow‐up will provide more information in symptom recurrence after stopping treatment. Wider implications of the findings: All linzagolix treatments provided sustained benefit. Two regimens previously identified for potential long‐term treatment, 200mg with ABT and 100mg without ABT, provided sustained improvements of anemia, pain and associated quality of life. These different treatment regimens could be important to address the diverse needs of women suffering from uterine fibroids.

Taylor, H. S., et al. (2022). "Post-treatment Efficacy and Safety Follow-up in Women with Uterine Fibroids Treated for 52 Weeks With Linzagolix." Obstetrics and Gynecology 139(SUPPL 1): 31S-32S.
	INTRODUCTION: We previously reported safety and efficacy results from the PRIMROSE 1 and 2 trials of linzagolix in the treatment of women with heavy menstrual bleeding associated with uterine fibroids (UFs), which showed maintenance of treatment effect for up to 52 weeks of dosing. Here we report post-treatment follow-up of key efficacy and safety results from weeks 64 and 76. METHOD(S): PRIMROSE1 and PRIMROSE2 were two randomized, double-blind, placebo-controlled phase 3 trials investigating the efficacy and safety of linzagolix 100 mg and 200 mg once daily, with or without hormonal add-back therapy (ABT) in the treatment of UFs for 52 weeks. Participants were followed for up to 6 months (week 76) after completion of treatment. RESULT(S): At week 64, improvements in pain, hemoglobin, healthrelated quality of life, and uterine and fibroid volumes, observed at 24 and 52 weeks, were diminished but a beneficial difference from baseline was maintained. In patients with amenorrhea at week 52, the median (95% CI) time to first uterine bleeding was 30 (SD 27; SD 32) and 31 (SD 29; SD 32) days in PRIMROSE 1 and 2, respectively. At week 76, participants had full or partial recovery of lumbar spine bone mineral density (BMD): with 53%, 52% and 64% for 100 mg, 100 mg+ABT and 200 mg+ABT, respectively in PRIMROSE1 and 59%, 80% and 67% in PRIMROSE2. CONCLUSION(S): Linzagolix effects persisted following treatment discontinuation, although there was partial return to baseline for all measured efficacy endpoints. BMD also improved. The return to menstruation was rapid.

Taylor, J. A., et al. (2022). "Association of hysterectomy and invasive epithelial ovarian and tubal cancer: a cohort study within UKCTOCS." BJOG : an international journal of obstetrics and gynaecology 129(1): 110-118.
	Objective: To investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer.; Design: Prospective cohort study.; Setting: Thirteen NHS Trusts in England, Wales and Northern Ireland.; Population: A total of 202 506 postmenopausal women recruited between 2001 and 2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014.; Methods: Multiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow up or 31 December 2014. Cox proportional hazards regression models were used to assess the association.; Main Outcome Measures: Invasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review.; Results: Hysterectomy with conservation of one or both adnexa was reported in 41 912 (20.7%; 41 912/202 506) women. Median follow up was 11.1 years (interquartile range 9.96-12.04), totalling >2.17 million woman-years. Among women who had undergone hysterectomy, 0.55% (231/41 912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160 594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (hazard ratio 0.98, 95% CI 0.85-1.13, P = 0.765).; Conclusions: This large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. These data are important both for clinical counselling and for refining risk prediction models.; Tweetable Abstract: Hysterectomy does not alter risk of invasive epithelial ovarian and tubal cancer. (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Taylor, S. E., et al. (2022). "Shifting the Soil: Metformin Treatment Decreases the Protumorigenic Tumor Microenvironment in Epithelial Ovarian Cancer." Cancers 14(9): 2298.
	Controversy persists regarding metformin's role in cancer therapy. Our recent work suggested metformin acts by impacting the tumor microenvironment (TME), normalizing the epigenetic profile of cancer-associated mesenchymal stem cells (CA-MSC). As CA-MSC can negatively impact tumor immune infiltrates, we evaluated metformin's impact on the human TME, focusing on the interplay of stroma and immune infiltrates. Tumor samples from (i) 38 patients treated with metformin and chemotherapy and (ii) 44 non-metformin matched controls were included in a tissue microarray (TMA). The TMA was used to compare the presence of CA-MSC, desmoplasia and immune infiltrates in the TME. In vitro and in vivo models examined metformin's role in alteration of the CA-MSC phenotype. The average percentage of CA-MSC was significantly lower in metformin-treated than in chemotherapy alone-treated tumors (p = 0.006). There were fewer regulatory T-cells in metformin-treated tumors (p = 0.043). Consistent with CA-MSC's role in excluding T-cells from tumor islets, the T-cells were primarily present within the tumor stroma. Evaluation of metformin's impact in vitro suggested that metformin cannot reverse a CA-MSC phenotype; however, the in vivo model where metformin was introduced prior to the establishment of the CA-MSC phenotype supported that metformin can partially prevent the reprogramming of normal MSC into CA-MSC. Metformin treatment led to a decrease in both the presence of protumorigenic CA-MSC and in immune exclusion of T cells, leading to a more immune-permissive environment. This suggests clinical utility in prevention and in treatment for early-stage disease and putatively in immune therapy.Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Taylor-Swanson, L. J., et al. (2022). "A systematic review of the effects of traditional East Asian medicine on symptom clusters during the menopausal transition." MedRxiv.
	Importance: Given that many midlife women use evidence-based non-pharmacologic interventions for symptom management during the menopausal transition and early postmenopause and that many women experience two or more symptoms (symptom cluster), it is important to review recent evidence on said interventions for symptom clusters. This review focuses on randomized clinical trials (RCTs) of traditional East Asian Medicine (TEAM), including acupuncture, acupressure, moxibustion, and Chinese herbal medicine, for hot flashes and one or more co-occurring symptoms experienced during peri- or post-menopause. Objective(s): The primary objective of the study was to review RCTs (published 2011-2021) of TEAM interventions for hot flashes and at least one other co-occurring symptom, including sleep problems, cognitive function, mood, and pain. Evidence Review: We searched Medline, CINAHL Plus, and PsychINFO for RCTs reported in English from July 7, 2011, to December 31, 2021. We included RCTs that assessed women in the menopausal transition or early postmenopause with masking as appropriate; TEAM interventions were studied as the treatment with one or more comparison groups; hot flushes and at least one additional symptom from at least one of the symptom clusters were reported as an outcome (from sleep, mood, cognition, pain symptom groups). Bias was assessed. Finding(s): Of 409 abstracts identified, 9 RCTs examined the effectiveness of therapies for hot flashes and at least one additional co-occurring symptom. One study reported separately on two TEAM interventions. The maximum trial duration was 6 months (range: 5 weeks - 6 months). Statistically significant improvement was reported in 2 or more symptoms: 5 of 6 studies of acupuncture, one acupressure study, one moxibustion study, 1 of 2 studies of Chinese herbal medicine. Conclusions and Relevance: Our systematic review summarizes the recent literature on TEAM interventions for symptom clusters during the MT and EPM. A majority of studies reported symptom reduction. Overall, our findings highlight the need for further investigation with studies that include whole systems TEAM as each intervention was studied separately in the reviewed trials. Clinical practice often includes concurrent use of acupuncture, moxibustion, CHM, and advice to patients to use self-acupressure. Studying each modality separately is a scientific abstraction that does not reflect clinical practice.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Taytum, K., et al. (2023). "Stopping Dysmenorrhea: A Systematic Review of Drugs for Uterine Contractions."
	
Tctr (2021). "Comparison of home-based Functional approach and Kegel exercise on quality of life in community dwelling postnatal women with stress urinary incontinence." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Active Comparator Other,Active Comparator Other Functional approach exercise has 5 position. In all position, deep breath in should be done from nose and breath out from mouth. 1. Relaxation and stretching of pelvic floor muscle and hip adductors (butterfly posture) for 5 minutes 2. 3‐months model with breathing, sagittal stabilization and functional joint centration: Chest and pelvis should be in parallel position where IAP is maintained At first therapist holds the leg on 90/90 position of hip and knee. After gaining control, participants hold leg by themselves. Participants should inhale breath, hold for 3 seconds and breath‐out, repeated for 10 times with 3 seconds rest after each repetition. (Mahdieh et al., 2020, Kobesova and Kolar, 2014, Kolar et al., 2013). 3. 5‐months model with breathing, sagittal stabilization, functional joint centration and isolated motion of upper extremity: Starting position: hook lying and leg holding at 90/90 of hip and knee, take hand towards the opposite knee without any movement of chest while breathing in and breath hold for 3 seconds. Breath‐out while taking hand back to the normal position. 10 repetition on both sides with 3 seconds rest after each repetition. (Mahdieh et al., 2020, Kolar et al., 2013). 4. 5‐months model with breathing, sagittal stabilization, functional joint centration and motion of lower extremity: Starting position was hook lying and leg holding at 90/90 of hip and knee. Breath in with abduction of leg, 3 sec breath hold, return back while breath out. 10 repetition on both sides, 3 seconds rest after every repetition. (Mahdieh et al., 2020, Kolar et al., 2013). 5. 12‐months model with breathing, sagittal stabilization, functional joint centration and closed kinetic chain: Spine upright with diaphragm and PFM parallel with each other. Squatting with breath i Functional approach,Kegel exercise CONDITION: 1.Functional approach; 2.Pelvic floor muscle training; 3.Quality of life; 4. Postnatal stress urinary incontinence; 5.Kegel exercise Stress urinary incontinence ; 1.Functional approach; 2.Pelvic floor muscle training; 3.Quality of life; 4. Postnatal stress urinary incontinence; 5.Kegel exercise PRIMARY OUTCOME: Quality of Life baseline and postmeasurement kings health questionnaire (KHQ) SECONDARY OUTCOME: Severity of Incontinence baseline and postmeasurement incontinence severity index,Leakage volume baseline and postmeasurement 24‐hour pad weight test,Frequency of micturition baseline and postmeasurement bladder Diary,Sagittal stabilization baseline and postmeasurement pressure Bio‐feedback unit INCLUSION CRITERIA: 1) Postnatal women with SUI evaluated by 3 Incontinence Questionnaire 2) Mild and moderate severity in SUI evaluated by Incontinence Severity Index score 1 to 6 3) Between three to twelve months after vaginal delivery 4) Body mass index less than thirty 5) Less than three vaginal delivery

Tctr (2021). "Efficacy of Sublingual administration Misoprostol 600 mcg versus 800 mcg for induced abortion in women with early pregnancy loss: a Randomized Controlled Trial." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: 600 mcg misoprosto,800 mcg misoprostol 600 mcg misoprostol sublingually administrated every 6 hours maximum 3 doses,800 mcg misoprostol sublingually administrated every 6 hours maximum 3 doses Active Comparator Drug,No Intervention Drug CONDITION: Early pregnancy loss; Medical abortion; Misoprostol Pregnant women which gestational age less than 12 weeks with early pregnancy loss. ; Early pregnancy loss; Medical abortion; Misoprostol PRIMARY OUTCOME: success rate within 7 days Transvaginal ultrasound after 7 days of administration of misoprostol SECONDARY OUTCOME: success rate within 7 days within 7 days after administration misoprostol, if ET less than 10mm defined as complete abortion which is success rate INCLUSION CRITERIA: 18‐year‐old pregnant women who were below 12 weeks of gestational age and diagnosed with an early pregnancy loss with stable vital signs, closed internal cervical os, no contraindication for misoprostol, no active bleeding, no abnormal pregnancy (ectopic pregnancy, molar pregnancy) were included

Tctr (2023). "Efficacy of vitamin D on vulvovaginal atrophy in menopausal women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Active Comparator Drug,Placebo Comparator No treatment ergocalciferol 20000 IU 1 cap po q monday, wednesday, friday * 12 weeks,placebo 1 cap po q monday, wednesday, friday * 12 weeks Vitamin D group,Placebo group CONDITION: menopausal women who have vulvovaginal atrophy ; vulvovaginal atrophy, menopausal women , vitamin D, vaginal maturation value, vaginal atrophy symptoms (The most bothersome symptom), modified vaginal health inde X, vaginal atrophy score , vitamin D level vulvovaginal atrophy, menopausal women , vitamin D, vaginal maturation value, vaginal atrophy symptoms (The most bothersome symptom), modified vaginal health inde X, vaginal atrophy score , vitamin D level PRIMARY OUTCOME: vaginal maturation value 12 weeks Histological SECONDARY OUTCOME: vaginal atrophy symptoms (The most bothersome symptom) 0, 6, 12 weeks Patient reported outcome using a questionnaire interview,modified vaginal health inde X0, 6, 12 weeks Physical examination,vaginal atrophy score 0, 6, 12 weeks Physical examination ,vitamin D level 0, 6, 12 weeks Electrochemiluminescence immunoassay (ECLIA) INCLUSION CRITERIA: 1. Women who have vulvovaginal atrophy symptoms, 2. Menopausal women, who absence of menstruation for at least 1 year, 3. Women who previous bilateral oophorectomy, 4. Women who have serum FSH level more than 40 IU/L

Techatraisak, K., et al. (2022). "Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN." Reproductive sciences (Thousand Oaks, Calif.) 29(4): 1157-1169.
	Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015. (© 2022. The Author(s).)

Tedesco, M., et al. (2023). "Efficacy of injecting hybrid cooperative complexes of hyaluronic acid for the treatment of vulvar lichen sclerosus: A preliminary study." Journal of cosmetic dermatology 22(2): 449-457.
	Background: Lichen sclerosus is a chronic relapsing inflammatory skin disease, which involves most commonly the anogenital region. The gold standard in treatment is ultra-potent topical steroids (clobetasol propionate): it aims at controlling the symptoms, stopping further scarring and distortion, and reducing the risk of cancer.; Objectives: The aim of this preliminary study is to evaluate the efficacy of injecting Hybrid Cooperative Complexes of Hyaluronic Acid (HCC) for the treatment of vulvar lichen sclerosus (VLS).; Methods: Twenty female adult patients (range: 21-78 years), aged over 18, with histopathological diagnosis of lichen sclerosus and good general conditions were enrolled. Patients underwent HCC infiltration every month, for 3 times. Patients were evaluated at baseline (T0) and after one (T1) and six months (T2) after treatment. During every visit, each patient was studied clinically and with videothermography. Itching, burning sensation, pain, and dyspareunia were reported by patients at T0, T1, and T2. The effectiveness of the treatment on patients' quality of life and sexual function was evaluated using the Dermatology Life Quality Index (DLQI) and the Female Sexual Function Index (FSFI) at T0 and at T2.; Results: The results of this preliminary study are very promising, in fact, all patients had a significant reduction in most symptoms after 1 and 6 months of HCC treatment. The reduction of patients with itching (p value ≤ 0.001), pain (p value = 0.031), and burning sensation (p = 0.004) at 6 months is significant. The analysis of DLQI scores revealed a significant improvement in patients' quality of life. At baseline, the average score of DLQI (±SD) was 5.89 ± 3.68 while at follow-up it was 3.42 ± 2.36 (p = 0.002).; Conclusions: Our preliminary study has demonstrated the validity and tolerability of HCC infiltrations in patients with VLS, and the effectiveness of HCC in reducing symptoms and, thus, to improve sexuality and patient quality of life. (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Teede, H., et al. (2019). "Effect of the combined oral contraceptive pill and/or metformin in the management of polycystic ovary syndrome: A systematic review with meta-analyses." Clinical Endocrinology 91(4): 479-489.
	Background: Polycystic ovary syndrome (PCOS) has a prevalence of 8%-13%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence-based guidelines are needed in PCOS management. This systematic review with meta-analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines.; Methods: Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta-analyses were conducted, where appropriate.; Results: Fifty-six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low-quality evidence in adolescents, meta-analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] -4.02 [-5.23, -2.81], P < 0.001); COCP was better than metformin for menstrual regulation (MD -0.19 [-0.25, -0.13], P < 0.00001). In low-quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], P = 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03). Combined oral contraceptive pill alone was better than the combination with an anti-androgen for BMI (MD -3.04 [-5.45, -0.64], P = 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI.; Conclusions: This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti-androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI ≥ 25 kg/m 2 . There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin. (© 2019 John Wiley & Sons Ltd.)

Tehrani, F. R. and M. Amiri (2019). "Polycystic ovary syndrome in adolescents: Challenges in diagnosis and treatment." International Journal of Endocrinology and Metabolism 17(3): e91554.
	Context: Despite the importance of timely diagnosis and treatment of polycystic ovary syndrome (PCOS) among adolescent females, considering the paucity of data focusing on this group and controversies documented on its recognition and management, the purpose of this review was to summarize challenges and recommendations of diagnosis and treatment for adolescents with PCOS. Evidence Acquisition: This review summarizes papers documented on PCOS among adolescent females. PubMed, Scopus, Web of Science, and Google Scholar databases were searched for retrieving studies conducted on PCOS among adolescent females up to March, 2019. The final selection of papers was made based on their relevancy with the fields of diagnosis and treatment of PCOS in this age group. Result(s): Oligo-anovulation in adolescents, if persistent, is a matter for concern. Hirsutism and moderate to severe acne in adolescent females should be considered as clinical manifestations of hyperandrogenism (HA). Diagnosis of biochemical HA in adolescents with PCOS requires reliable tests using well-defined normal ranges. In adolescent females, an elevated androgen level (hyperandrogenemia) alone is not enough to detect HA, unless it is persistent and associated with anovulation. Metabolic disorders should not be used as diagnostic criteria of PCOS among adolescent females. Re-assessment of all adolescent females with probable PCOS, using reliable diagnostic criteria, is needed to avoid over diagnosis and unnecessary treatment in healthy normal females without HA. In adolescent females with PCOS, the main clinical problem is the control of menstrual irregularity and hirsutism; treatment approaches for these patients are primarily directed at the major clinical manifestations and complaints. Lifestyle modifications are baseline interventions, which can be added to special treatments, such as Oral Contraceptives (OCs), metformin, or antiandrogens for most adolescents with PCOS, particularly those with overweight or obesity. Conclusion(s): This review emphasizes the use of standard diagnostic criteria for PCOS, developed for adolescents. Although early recognition and management of PCOS in adolescents can prevent long-term complications associated with this syndrome, clinicians should re-evaluate all such patients with features very similar to PCOS to avoid over/incorrect diagnosis using precise criteria, suggested for this age group.Copyright © 2019, International Journal of Endocrinology and Metabolism.

Tehraninejad, E. S., et al. (2021). "Comparison of assisted reproductive technology cycle outcomes among daily buserelin, daily, and every other day triptorelin in infertile patients referring to imam khomeini hospital complex: a randomized controlled trial." International Journal of Women's Health and Reproduction Sciences 9(1): 49‐54.
	Objectives: Different types of gonadotropin‐releasing hormone (GnRH) agonist protocols are used in assisted reproductive technology (ART) cycles although the role of every other day GnRH agonist administration is not well understood. Thus, this study compared the effectiveness of different ways of the administration of GnRH agonists in the ovarian stimulation long protocol and their effects on in vitro fertilization (IVF) outcomes. Materials and Methods: In a randomized controlled trial (RCT), 138 patients were randomly assigned to 3 groups with 46 patients. In group A, patients were treated with daily buserelin 0.5 mg subcutaneously and those in group B were treated with triptorelin 0.1 mg daily, and finally, patients in group C received triptorelin 0.1 mg every other day (all under a long protocol). Eventually, controlled ovarian stimulation was performed with the follicle‐stimulating hormone (FSH). Results: There was no significant difference in biochemical and clinical pregnancy, along with abortion and twin rates between the comparison groups. Meanwhile, the number of gonadotropin injections was significantly lower in group C (P = 0.033). Moreover, the number of follicles and days of ovarian stimulation did not have a significant difference between study groups. Finally, the number of metaphase 2 oocytes and embryos was significantly higher in group A (P = 0.001). Conclusions: In general, pregnancy and abortion rates did not significantly differ between the comparison groups and, the number of gonadotropin injections was significantly lower in the triptorelin 0.1 mg every other day group. Thus, our finding revealed that every other day use of triptorelin 0.1 mg, comparing its daily use or daily buserelin, might be cost‐benefit.

Teigné, D., et al. (2022). "Cervical cancer screening uptake: A randomized controlled trial assessing the effect of sending invitation letters to non-adherent women combined with sending their general practitioners a list of their non-adherent patients (study protocol)." Frontiers in Public Health 10: 1035288.
	Introduction: Cervical cancer (CC) is the fourth most common cancer among women. It can be cured if diagnosed at an early stage and treated promptly. The World Health Organization suggests that 70% of women should be screened with a high-performance test by the age of 35. This paper reports a protocol to assess the effect of two modalities of organized CC screening programmes on CC screening uptake.; Methods and Analysis: Design and setting: The design involves a 3-arm randomized controlled study performed in a French geographic area on the west coast. A total of 1,395 general practitioners will be randomized, depending on their general practice surgeries. Participants: The design is based on a total of 94,393 women aged 40 to 65 years who are eligible for CC screening. Intervention: In the "optimized cancer screening" group, the intervention will combine sending invitation letters to non-adherent women with sending general practitioners (GPs) a list of their non-adherent patients. In the "standard cancer screening" group, the intervention will be limited to sending invitation letters to non-adherent women. In the "usual care" group, no letter will be sent either to women or to their GPs. Primary endpoint: CC screening test uptake will be assessed after a 6-month follow-up period. Statistical analysis: The percentage of women who are up-to-date with their screening at 6 months after the intervention will be compared across arms using a generalized mixed linear model.; Discussion: A large-scale randomized trial of this nature is unprecedented. The study will enable us to assess a strategy relying on GPs, identified as the coordinators in this screening strategy. The study results should help policy makers to implement organized CC screening programs in the future.; Ethics and Dissemination: The study was approved was approved by the Ethics Committee of the National College of Teaching General practitioners (IRB00010804). It was recorded in ClinicalTrials.gov on the number NCT04689178 (28 December 2020). The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Teigné, Banaszuk, Grimault, Abes, Gaultier and Rat.)

Tejpal, C., et al. (2019). "Is Metformin the Answer for Distressed Females with Menstrual Irregularities?" Cureus 11(8): e5460.
	This literature review is aimed to determine if metformin alone improves menstrual irregularities in females with the polycystic ovarian syndrome. The current literature review involves females with polycystic ovarian syndrome experiencing menstrual irregularity. The data was collected in PubMed and inclusion criteria included articles published in the past 10 years, articles involving only humans, articles written in the English language and considering women age 19 or more. The number of discovered articles was 1550 after the first search and only 25 articles that met the inclusion criteria were selected after quality assessment. The selected 25 articles that met the inclusion criteria after a review showed evidence for regulating menstrual cycles with metformin therapy alone among females with the polycystic ovarian syndrome. When metformin was used in addition to other pharmacologic agents, there was a more significant restoration of menstrual cycles. Monotherapy with metformin is found to be highly effective in treating menstrual irregularities experienced among patients with the polycystic ovarian syndrome. Greater improvement was noted with the addition of another agent to metformin.

Telek Savci, B., et al. (2022). "Oral Gonadotropin-Releasing Hormone Antagonists in the Treatment of Uterine Myomas: A Systematic Review and Network Meta-analysis of Efficacy Parameters and Adverse Effects." Journal of Minimally Invasive Gynecology 29(5): 613-625.
	Objective: The aim of this systematic review is to gather and synthesize evidence regarding the use of oral gonadotrophin-releasing hormone (GnRH) antagonist for the treatment of bleeding associated with uterine myomas.; Data Sources: Web of Science, and MEDLINE databases were searched electronically on March 5, 2021, using combinations of the relevant Medical Subject Headings terms and keywords. The search was restricted to the English language and to human studies.; Methods of Study Selection: Only randomized controlled trials involving patients with heavy menstrual bleeding associated with uterine myomas treated with different doses of oral nonpeptide GnRH antagonists with or without add-back therapy were included. Studies comparing oral nonpeptide GnRH antagonists with treatments other than placebo were also excluded.; Tabulation, Integration, and Results: A total of 5 randomized trials including 2463 women were included in the analyses. Included studies were found to be at low risk of bias. When treatments were compared against placebo, the top 3 treatments for bleeding suppression were elagolix 600 mg, 400 mg, and 200 mg without add-back. Elagolix 600 mg without add-back therapy had a significantly higher risk of amenorrhea than lower doses of elagolix with and without add-back and relugolix as well. Uterine volume changes were more pronounced in therapies without add-back. All treatments were associated with significantly improved quality of life scores, both for myoma symptom-related and overall health-related scores. With the exception of relugolix with high-dose add-back, all treatments significantly increased low-density lipoprotein (LDL) levels. Again, all treatment modalities except for elagolix 200 mg without add-back significantly increased LDL-to-HDL ratio. The increase was highest for treatment without add-back therapy.; Conclusion: Oral GnRH antagonists seem to be effective for myoma-associated bleeding and for improving quality of life. The safety profile is acceptable for short-term use, but lipid metabolism is affected. (Copyright © 2022. Published by Elsevier Inc.)

Tempfer Clemens, B., et al. (2019). "Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for endometrial cancer-derived peritoneal metastases: a systematic review." Clinical & experimental metastasis 36(4): 321-329.
	Cytoreductive surgery (CRS) is an appropriate treatment for selected patients with endometrial cancer (EC)-derived peritoneal metastases (PM). Hyperthermic intraperitoneal chemotherapy (HIPEC) may enhance the therapeutic efficacy of CRS in these patients. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials and case reports reporting on the safety and efficacy of CRS and HIPEC in patients with EC-derived PM. Eight publications reporting on 68 patients were identified. The mean patient age was 57.1 years and the mean time from initial treatment of EC to CRS and HIPEC was 22.3 months. 41/64 patients had adenocarcinomas, type II cancers were present in 23/64 patients. The mean peritoneal carcinomatosis index (PCI) was 16.7. A complete surgical resection CC-0 was achieved in 44/63 (70%) patients. The chemotherapy regimens used for HIPEC were variable, but all included cisplatin, administered either alone (39/68 patients) or combined with doxorubicin or paclitaxel or mitomycin (29/68 patients). The duration of HIPEC was 60 min in 51/68 patients and 90 min in 17/68 patients. Mostly, the closed technique was used (55/68 patients). Adverse events grades 1/2, 3, and 4 were observed in 23/63, 12/63, and 6/63 patients, respectively. Treatment-associated mortality was 1% (1/63). After CRS and HIPEC, most patients received systemic chemotherapy (46/63 patients). Median disease-free and overall survival ranged from 7 to 18 and 12 to 33 months, respectively. In conclusion, CRS and HIPEC in EC with PM is safe and feasible. An additional therapeutic value of HIPEC is suggested, but prospective comparative trials are warranted.

Temtanakitpaisan, T., et al. (2022). "Prophylactic antibiotics for preventing infection after continence surgery in women with stress urinary incontinence." Cochrane Database of Systematic Reviews 2022(3): CD012457.
	Background: Surgical options for treating stress urinary incontinence (SUI) are usually explored after conservative interventions have failed. Surgeries fall into two categories: traditional techniques (open surgery) and minimally invasive procedures, such as laparoscopic procedures, midurethral sling and injections with urethral bulking agents. Postsurgery infections, such as infections of the surgical site or urinary tract, are common complications. To minimise the risk of postoperative bacterial infections, prophylactic antibiotics may be given before or during surgery. Objective(s): To assess the effects of prophylactic antibiotics for preventing infection following continence surgery in women with stress urinary incontinence. Search Method(s): We searched the Cochrane Incontinence Specialised Register, which contains trials identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov and WHO ICTRP; and handsearched journals and conference proceedings to 18 March 2021. We also searched the reference lists of relevant articles. Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs assessing prophylactic antibiotics in women undergoing continence surgery to treat SUI. Data Collection and Analysis: Two review authors selected potentially eligible trials, extracted data and assessed risk of bias. We expressed results as risk ratios (RR) for dichotomous outcomes and as mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. Main Result(s): We identified one quasi-RCT and two RCTs, involving a total of 390 women. One study performed retropubic urethropexy surgery requiring a transverse suprapubic incision, while the other two studies performed midurethral sling surgery. It should be noted that none of the included studies clearly specified the timing of outcome assessment. We are very uncertain whether prophylactic antibiotics (cefazolin) have an effect on surgical site infections (RR 0.56, 95% CI 0.03 to 12.35; 2 studies, 85 women; very low-certainty evidence) or urinary tract infections or bacteriuria (RR 0.84, 95% CI 0.05 to 13.24; 2 studies, 85 women; very low-certainty evidence). The effect of prophylactic antibiotics (cefazolin) on febrile morbidity is also uncertain (RR 0.08, 95% CI 0.00 to 1.29; 2 studies, 85 women; very low-certainty evidence). We are very uncertain whether prophylactic antibiotics (cefazolin) have any effect on mesh exposure (RR 0.32, 95% CI 0.01 to 7.61; 1 study, 59 women; very low-certainty evidence). None of the three included studies described the assessment of adverse events from antibiotic use, sepsis or bacteraemia in their reports. Authors' conclusions: Only limited data are available from the three included studies and, overall, the certainty of evidence was very low. Moreover, the three included studies evaluated different surgical procedures and dosages of antibiotic administration. Thus, there is insufficient evidence to support or refute the use of prophylactic antibiotics to prevent infection following anti-incontinence surgery. In addition, there were no data regarding adverse effects of prophylactic antibiotics. More RCTs are required.Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Ten, J., et al. (2022). "Sperm DNA fragmentation on the day of fertilisation is not associated with assisted reproductive technique outcome independently of gamete quality." Human fertility (Cambridge, England) 25(4): 706-715.
	The evaluation of sperm DNA fragmentation has been postulated as a predictive molecular parameter of the semen fertilising potential, as well as the ability to give rise to a healthy embryo and an ongoing pregnancy. However, there are controversial results due to oocyte quality, the use of different measurement techniques and interpretation criteria. Our objective is to investigate if sperm DNA fragmentation on the day of fertilisation influences in vitro fertilisation (IVF) outcome in a prospective double-blind study. Three groups of patients were defined: (i) 68 couples undergoing intracytoplasmic sperm injection (ICSI) due to severe male factor with normal ovarian response (NOR); (ii) 113 couples undergoing conventional in vitro fertilisation (IVF) in our oocyte donation programme due to ovarian failure; and (iii) 150 low ovarian response (LOR) patients undergoing ICSI or IVF. TUNEL assay was performed from an aliquot of each capacitated semen sample to detect DNA fragmentation. There was no relationship between blood serum β-hCG positive test, clinical pregnancy and first trimester miscarriage with DFI levels in NOR ( p = 0.41, p = 0.36, p = 0.40), recipient ( p = 0.49, p = 0.99 and p = 0.38) and LOR ( p = 0.52, p = 0.20, p = 0.64) groups of patients, respectively. Therefore, ART outcomes are not affected by sperm DNA fragmentation independently of gamete quality.

Teng, W., et al. (2023). "Effect of sequential embryo transfer on in vitro fertilization and embryo transfer outcomes: a systematic review and meta-analysis." Frontiers in Medicine 10: 1303493.
	Background: Sequential embryo transfer has been recognized as a strategy to increase pregnancy rates in women undergoing in vitro fertilization and embryo transfer (IVF-ET). However, its impact on assisted reproductive outcomes remains to be substantiated by robust evidence. This systematic review aims to summarize and analyze the available evidence to investigate the effect of sequential embryo transfer on assisted reproductive outcomes. Method(s): A comprehensive literature search was executed across the Pubmed, Cochrane Library, Web of Science, and Scopus databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were aggregated utilizing a random effects model, and the resultant outcomes were articulated as odds ratios (ORs) along with their 95% confidence intervals (CIs). Result(s): The pooled results revealed a statistically significant enhancement in reproductive outcomes for infertile patients undergoing sequential embryo transfer as evidenced by elevated rates of chemical pregnancy (OR = 1.67, 95% CI = 1.23-2.27), clinical pregnancy (OR = 1.78, 95% CI = 1.43-2.21), and ongoing pregnancy (OR = 1.54, 95% CI = 1.03-2.31). Compared with cleavage-stage embryo transfer, sequential transfer yielded superior outcomes in terms of chemical pregnancy rate (OR = 2.08, 95% CI = 1.35-3.19) and clinical pregnancy rate (OR = 1.78, 95% CI = 1.37-2.31). Furthermore, among the repeated implantation failure (RIF) cohort, sequential embryo transfer surpassed blastocyst-stage transfer, delivering a heightened chemical pregnancy rate (OR = 1.66, 95% CI = 1.19-2.53) and clinical pregnancy rate (OR = 1.65, 95% CI = 1.19-2.27). Conclusion(s): Our meta-analysis indicates that sequential transfer may enhance clinical pregnancy rate in a small subgroup of well-selected women. While promising, further evidence from prospective studies is needed.Copyright © 2023 Teng, Xian, Wang, Wang, Meng, Zhang, Shan and Yi.

Tengfei, Y., et al. (2023). "Impact of insulin resistance on ART outcomes in women with polycystıc ovary syndrome: a systematic review and meta-analysis."
	
Tennfjord Merete, K., et al. (2021). "Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review." BMC Women's Health 21(1): 355.
	Background: Endometriosis is a common benign gynecological disease that has the potential to debilitate due to pain and reduced quality of life. Treatment modalities such as hormones and surgery have limitations and do not treat all dimensions of the problems caused by endometriosis, and physical activity (PA) and exercise have been suggested as alternative treatments. Aim of this study was to perform a systematic review and meta-analysis to assess the effect of PA and exercise on endometriosis-associated symptoms.; Methods: Eleven databases were searched systematically. Study selection, quality assessment, and data extraction were carried out by two independent researchers in accordance with PRISMA guidelines. Eligibility criteria were women with diagnosed endometriosis receiving an intervention (PA and/or exercise). The primary outcome was pain intensity, but all outcomes were accepted.; Results: This study screened 1045 citations for eligibility. Four interventional studies were identified, of which one showed fatal design flaws and so was excluded. Three studies, two randomized controlled trials (RCT) and one pre-post study with no control group, involving 109 patients were included in a descriptive synthesis. The interventions included flexibility and strength training, cardiovascular fitness, and yoga, and were performed from one to four times per week for a total duration of 8-24 weeks, with or without supervision. Only one study found improvements in pain intensity. One study showed decreases in stress levels. Due to the heterogeneity of the study outcomes and measures, as well as confounding factors, a quantitative meta-analysis could not be performed.; Conclusion: The effect of PA and exercise as treatments for endometrioses-associated symptoms could not be determined due to significant limitations of the included studies. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools.; Trial Registration Number: CRD42021233138. (© 2021. The Author(s).)

Teresa, E. F. P., et al. (2023). "Effectiveness of physiotherapy techniques for treatment of dyspareunia : a systematic review."
	
Terho, A., et al. (2022). "Laparoscopically guided transversus abdominis plane block versus local wound analgesia in laparoscopic surgery for peritoneal endometriosis: study protocol for a prospective randomized controlled double-blinded LTAP-trial." Trials 23(1): 55.
	Background: Ultrasound-guided transversus abdominis plane block (TAP) performed by anesthesiologist has been shown to be an effective and safe analgesia method in abdominal surgery, reducing postoperative opioid consumption. Recently, there has been growing interest to insert TAP under laparoscopic vision (LTAP) by surgeon. LTAP has been used in laparoscopic gastrointestinal surgery, but studies on LTAP in gynecologic laparoscopic surgery are sparse and inconsistent. The purpose of this study is to compare the efficacy of LTAP and local wound analgesia in laparoscopic surgery due to suspected or diagnosed superficial peritoneal endometriosis.; Methods: The LTAP-trial is a prospective randomized controlled double-blinded study comparing the efficacy and safety of LTAP with local wound analgesia in laparoscopic endometriosis surgery. Patients are randomized to receive LTAP with levobupivacaine and wound infiltration with placebo or wound infiltration with levobupivacaine and LTAP with placebo. The primary outcome is postoperative opioid consumption measured by patient-controlled analgesia (PCA) pump. Secondly, subjective postoperative pain up to 24 h postoperatively will be measured by Numeric Rating Scale (NRS). Additional outcome measures are factors related to recovery and length of stay in the hospital as well as a 6-month follow-up survey regarding pain (NRS) and endometriosis-related wellbeing (endometriosis-related health profile, EHP-30) after surgery. A total of 46 patients will be randomized in a proportion of 1:1.; Discussion: Patients with peritoneal endometriosis are often prone to severe postoperative pain that may prohibit their enhanced recovery after laparoscopy. Thus, there is a need for effective postoperative pain management with minimal side-effects. This study focusing on laparoscopically inserted transversus abdominis plane block may provide new insight in dealing with postoperative pain after laparoscopic endometriosis surgery as well as after other gynecologic surgery.; Trial Registration: The LTAP-trial -protocol has been prospectively registered to ClinicalTrials.gov , ID: NCT04735770 . Registered on February 2021. (© 2022. The Author(s).)

Terrassa Hospital Mutua, d. and o. Barcelona University (2022). E-health Intervention for Improving Mental Health During Pregnancy Using Virtual Reality.
	No Results Available Device: Immersive Virtual Reality (IVR) Depression in pregnand women|Anxiety in pregnand women|Symptom checklist -90-R Female Not Applicable 150 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 02/2018 December 30, 2024

Tersigni, C., et al. (2024). "Oral administration of Bifidobacterium longum ES1 reduces endometrial inflammation in women with recurrent pregnancy loss." American journal of reproductive immunology (New York, N.Y. : 1989) 91(1): e13804.
	Background: Over-activation of endometrial inflammasome NALP-3 (Nod-like receptor family pyrin domain containing 3) can be found in recurrent pregnancy loss (RPL) women probably due to leaky gut and passage into circulation of lipopolysaccharides (LPS). Leaky gut can be caused by exposure to gluten in RPL women genetically predisposed to celiac disease, positive for Human Leukocyte Antigen (HLA)-DQ2/DQ8 haplotype. Oral administration of Bifidobacterium longum ES1 (GliadinES®) can inactivate gluten peptides toxicity to epithelial gut cells and improve gut barrier.; Methods: We investigated by enzyme-linked immunoassay: (a) serum levels of LPS and zonuline (a marker of leaky gut); (b) LPS, NALP-3, caspase-1, interleukine (IL)-1β and IL-18 concentration in endometrial fluids, in untreated women with uncomplicated pregnancies (negative HLA-DQ2/DQ8 haplotype) (n = 22) and in women with unexplained RPL, HLA-DQ2/DQ8 positive (n = 22), before and after daily oral administration for 3 months of GliadinES®.; Results: RLP women showed higher serum levels of LPS (p < 0.0001) and higher concentration of LPS (p < 0.0001), NALP-3 (p < 0.01); Caspase-1 (p < 0.0001), IL-1β (p < 0.0001), and IL-18 (p < 0.0001) in endometrial fluids compared to controls. GliadinES® treatment significantly reduced serum levels of both LPS (p < 0.0001) and zonuline (p < 0.01), as well as LPS (p < 0.5), NALP-3 (p < 0.01), Caspase-1 (p < 0.001), IL-1β (p < 0.001), and IL-18 (p < 0.01) concentrations in endometrial fluids of RPL women.; Conclusions: RPL women positive for HLA-DQ2/DQ8 haplotype show increased circulating and endometrial levels of LPS and endometrial inflammasome NALP-3 over-activation. Oral administration of GliadinES® can reduce gut permeability, decrease serum levels of LPS and, contextually, improve endometrial inflammation in this specific subset of RPL women. (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Terzic, M., et al. (2023). "Reproductive and Obstetric Outcomes after Fertility-Sparing Treatments for Cervical Cancer: Current Approach and Future Directions." Journal of Clinical Medicine 12(7): 2614.
	Cervical cancer is one of the leading causes of cancer-related death in women of reproductive age. The established fertility-sparing approaches for the management of early-stage cervical cancer for women who plan pregnancy are associated with a decline in fecundity and an increased risk of pregnancy complications. This article aims to offer an overview of fertility-sparing approaches and the management of potential subfertility and pregnancy complications after these treatments. An extensive search for the available data about infertility and cervical cancer, fertility-sparing techniques in patients with cervical cancer, fertility treatment, obstetrical complications, and pregnancy outcomes in cervical cancer patients was completed. Fertility-preserving procedures such as loop electrosurgical excision procedure (LEEP), cold-knife conization, and trachelectomy in women diagnosed with cervical cancer can be considered as safe and effective treatments that preserve reproductive potential. Current fertility-preserving procedures, based on the balance of the oncological characteristics of patients as well as their desire for reproduction, allow one to obtain acceptable reproductive and obstetric outcomes in women treated for cervical cancer. Nevertheless, careful monitoring of pregnancies obtained after fertility-preserving procedures is recommended, since this cohort of patients should be considered at higher risk compared with a healthy population.Copyright © 2023 by the authors.

Tesfaye, T. and Y. Aman (2022). "Safety, and effectiveness of self-sourcing of medications for induced abortion. A systematic review."
	
Tessel, C., et al. (2021). "The stage of implementation of transvaginal radiofrequency ablation methods for uterine leiomyomas according to the IDEAL framework; a systematic review."
	
Tessier, L., et al. (2023). "LAPAROSCOPIC OVARIAN TRANSPOSITION PRIOR TO PELVIC RADIATION IN YOUNG FEMALE PATIENTS WITH PELVIC GASTROINTESTINAL MALIGNANCIES." Diseases of the Colon and Rectum 66(6): e424.
	Purpose/Background: Young women undergoing radiation therapy for pelvic malignancies are at risk of developing premature ovarian insufficiency. Ovarian transposition aims to preserve ovarian function in these patients. However, its role in gastrointestinal malignancy has yet to be firmly established. The aim of this review was to determine the effectiveness of laparoscopic ovarian transposition in preserving ovarian function in premenopausal women undergoing neoadjuvant pelvic RT for gastrointestinal malignancies. Methods/Interventions: Medline, EMBASE, and CENTRAL were systematically searched from inception through to May 2022. Articles were included if they evaluated ovarian function after OT before RT in women with gastrointestinal malignancies. The primary outcome was ovarian function preservation. The secondary outcome was thirty-day postoperative morbidity following OT. A DerSimonian and Laird inverse variance random-effects meta-analysis of proportions was used to generate the overall effect size of each outcome along with their respective 95% confidence intervals (CI) to confirm the effect size estimate. Results/Outcome(s): From 207 citations, 10 studies with 133 patients with rectal or anal cancer who underwent OT prior to RT were included. Meta-analysis of pooled proportions of preserved ovarian function demonstrates an incidence of 66.9% (95%CI 55.0-79.0%, I2=43%). The thirty-day postoperative morbidity rate was 1.2% (n=1). There was heterogeneity in interventions and outcome reporting. Conclusions/Discussion: Laparoscopic OT in premenopausal patients undergoing pelvic radiation for gastrointestinal malignancies can preserve ovarian function in two thirds of patients (66.9%, 95%CI 55.0-79.0%, I2=43%). The pooled data and meta-analyses must be interpreted within the context of clinical heterogeneity of the included studies. Further studies are required to fully investigate the outcomes of OT in patients undergoing pelvic radiation for gastrointestinal malignancies.

Tewari, K. S., et al. (2022). "Pembrolizumab + chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer: Subgroup analysis of KEYNOTE-826." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: In KEYNOTE-826 (NCT03635567),pembrolizumab (pembro) + chemotherapy (chemo) +/- bevacizumab (bev) provided statistically significant, clinically meaningful PFS and OS improvements in patients with persistent, recurrent, or metastatic cervical cancer. In the present analysis of KEYNOTE-826, we assessed outcomes in several key patient subgroups. Method(s): Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemo and not amenable to curative treatment; measurable disease per RECIST v1.1; ECOG PS 0-1; and a tumor sample to determine PD-L1 status. Patients were randomized 1:1 to pembro 200 mg Q3W or placebo (pbo) for up to 35 cycles + chemo (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) +/- bev 15 mg/kg. Dual primary endpoints are PFS by investigator assessment per RECIST v1.1 and OS in patients with PD-L1 CPS >=1, all comers, and CPS >=10. Treatment effects on PFS and OS were examined in patient subgroups defined by bev use (yes or no), histology (squamous or non-squamous [including adenocarcinoma and adenosquamous]), platinum use (carboplatin or cisplatin), and prior chemoradiation therapy (CRT). Hazard ratios (HR) and 95% CIs were based on a stratified Cox regression model. Result(s): 617 patients were randomized (pembro + chemo +/- bev, n=308; pbo + chemo +/- bev, n=309). At the May 3, 2021 data cutoff, median follow-up was 22 months. Pembro + chemo prolonged PFS and OS vs pbo + chemo in all subgroups evaluated in the all-comer population (Table). Similar benefits of pembro + chemo on PFS and OS were also seen in the protocol-specified CPS >=1 and CPS >=10 populations. Conclusion(s): Pembro + chemo +/- bev prolonged PFS and OS vs pbo + chemo +/- bev among the subgroups defined by bev use, histology, platinum use, and prior CRT and provided clinically meaningful benefits similar to the broader population of patients with persistent, recurrent, or metastatic cervical cancer.

Tewari, K. S., et al. (2024). "Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial." JAMA Oncology 10(2): 185-192.
	IMPORTANCE The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown. OBJECTIVE To assess efficacy outcomes in patient subgroups of KEYNOTE-826. DESIGN, SETTING, AND PARTICIPANTS Exploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021. INTERVENTIONS Pembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 [area under the free carboplatin plasma concentration vs time curve]) with or without bevacizumab, 15 mg/kg. MAIN OUTCOMES AND MEASURES Overall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1-positive tumors (defined as a combined positive score [CPS] >=1) and in the intention-to-treat population. RESULTS A total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations. CONCLUSIONS AND RELEVANCE The findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer.Copyright © 2023 American Medical Association. All rights reserved.

Texeira, L. H., et al. (2022). "Minimally Invasive Sacrocolpopexy (Laparoscopic and Robotic): Its Outcomes and Complications-Our Experience." Journal of South Asian Federation of Obstetrics and Gynaecology 14(3): 261-264.
	Introduction: The gold standard treatment for managing patients with pelvic organ prolapse (POP) is sacrocolpopexy. Initially, open sacrocolpopexy was adopted; however, over the years classic laparoscopic approach and its modifications in the form of single port laparoscopy, NOTES (vaginal-assisted laparoscopy) and robotic-assisted laparoscopic sacrocolpopexy (LSC) have emerged. Usage of minimally invasive approaches has gained momentum in the recent past as they reduce the morbidity associated with open sacrocolpopexy, allowing faster recovery of the patient. Classic LSC has similar outcomes to abdominal sacrocolpopexy but is technically challenging especially due to the pelvic organ surgery offering limited area available for operating. Overcoming these limitations, by the characteristic features of the robotic system such as a "simulated wrist" of the mechanical arm with its enhanced freedom of movement along with a three-dimensional field of view, has attracted significant interest in recent years for robotic sacrocolpopexy (RSC). Aim(s): To evaluate outcomes and complications following minimally invasive sacrocolpopexy in patients with POP. Material(s) and Method(s): We evaluated a total of 20 patients with POP, 15 of those underwent LSC and five patients underwent RSC. We assessed outcomes in both these groups in terms of operating times, blood loss, blood transfusion, surgery-related complications, total hospital stay, and recurrence rates at 1-year follow-up. Result(s): Patients having RSC had a significantly lower rate of blood loss of <=300 mL. Maximum postoperative complications were recorded as Clavien-Dindo grade I (seen in 75% of the patients). Most common among these were dysuria and urinary infection (seen in 40%). No Clavien-Dindo grade IVa, IVb, and V complications were recorded in either laparoscopic or robotic techniques conducted at our hospital. At 1 year of follow-up, no significant recurrence was seen in RSC (0%), while a low recurrence rate was seen in LSC (two patients, 13%). Conclusion(s): Robotic technology provides some advantages as compared to classic laparoscopic surgery. However, both approaches appear to provide equivalent clinical outcomes. But the cost of utilizing and maintaining the robotic system appears to be significant. Hence LSC is the suitable method of treating POP, especially in a country like India. However large randomized trials comparing both techniques are warranted.Copyright © The Author(s).

Thaker, P. H., et al. (2021). "GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-escalation Study." Clinical Cancer Research 27(20): 5536-5545.
	Purpose: GEN-1 (phIL-12-005/PPC), an IL12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, has preclinical activity when combined with platinum-taxane intravenous chemotherapy and administered intraperitoneally in epithelial ovarian cancer (EOC) models. OVATION I was a multicenter, nonrandomized, open-label phase IB trial to evaluate the safety, preliminary antitumor activity, and immunologic response to GEN-1 in combination with neoadjuvant chemotherapy (NACT) carboplatin-paclitaxel in patients with advanced EOC. Patients and Methods: A total of 18 patients with newly diagnosed stage IIIC and IV EOC were enrolled. A standard 33 dose-escalation design tested four GEN-1 doses (36, 47, 61, 79 mg/m2) to determine the maximum tolerated dose and dose-limiting toxicities (DLTs). GEN-1 was administered in eight weekly intraperitoneal infusions starting at cycle 1 week 2 in combination with three 21-day cycles of NACT carboplatin AUC 6 and weekly paclitaxel 80 mg/m2. Result(s): The most common treatment-emergent adverse events at least possibly related were nausea, fatigue, abdominal pain/cramping, anorexia, diarrhea, and vomiting. Eight patients experience grade 4 neutropenia attributed to NACT. No DLTs occurred. A total of 14 patients were evaluable for response and 12 (85.7%) had radiological response (two complete response and 10 partial response) prior to debulking; nine were R0 at debulking and one patient had complete pathologic response. IL12 and its downstream cytokine, IFNg, increased in peritoneal washings but not as much in blood. Increased levels of myeloid dendritic cells and T-effector memory cells in peritoneal fluid, plus elevated CD8 T cells and reduced immunosuppression within the tumor microenvironment were found. A median time to treatment failure of 18.4 months (95% confidence interval, 9.2-24.5) was observed in the intention-to-treat population. Conclusion(s): Adding GEN-1 to standard NACT is safe, appears active, and has an impact on the tumor microenvironment.Copyright ©2021 The Authors; Published by the American Association for Cancer Research

Thakur, D., et al. (2021). "Effect of yoga on polycystic ovarian syndrome: A systematic review." Journal of Bodywork and Movement Therapies 27: 281-286.
	Polycystic Ovarian Syndrome (PCOS) is not a disease but a mere syndrome. Many researchers have studied polycystic ovarian syndrome and found that there is no proper cause of that, it may occur due to hormonal imbalance or stress, or due to a sedentary lifestyle. The rate of polycystic ovarian syndrome in Indian women has been increasing rapidly. The symptoms include acne, weight gain, hirsutism, difficulties in fertility, irregular or infrequent periods, immature ovarian eggs that do not ovulate, multiple cysts in the ovary. If left untreated, it may become the cause for heart diseases, diabetes, hypertension, infertility, and even cancer. There are varieties of medical treatments available to treat polycystic ovarian syndrome but they have a temporary effect and if taken for a long time then it may lead to serious side effects. Yoga has proven effects in reducing and managing the symptoms of polycystic ovarian syndrome more effectively along with medicine. This review work has been designed to consider the available literature concerning the effectiveness of yoga in the management of the polycystic ovarian syndrome. It includes some research papers published between 2012 and 2019. By providing yogic treatment effect on several parameters (such as blood lipid level, glucose metabolism, endocrine parameters, quality of life, resting cardiovascular parameters, level of anxiety, depression) on the woman with polycystic ovarian syndrome were measured. After thoroughly studying about 74 research papers, 16 are found most relevant to be reviewed. The studies of these papers concluded the successful use of different yogic limbs for the management of polycystic ovarian syndrome with or without medications. (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Thakur, N., et al. (2024). "Comparative Analysis of VMAT and IMRT Techniques: Evaluation of Dose Constraints and Bone Marrow Sparing in Cervical Cancer Patients Undergoing Chemoradiotherapy." Asian Pacific journal of cancer prevention : APJCP 25(1): 139-144.
	BACKGROUND: Carcinoma of the cervix is a globally significant cause of morbidity and mortality among women. Concurrent chemoradiotherapy, a standard approach for locally advanced cervical cancer, invariably involves pelvic irradiation. Although this strategy is effective, it inevitably affects the pelvic bone marrow, a crucial hematopoietic site, and leads to hematological toxicity The potential of IMRT to spare bone marrow in pelvic irradiation settings has been an area of significant interest, with the aim to mitigate the hematological toxicity associated with pelvic radiotherapy. Radiotherapy techniques have evolved in terms of conformity and normal tissue sparing. Our study intends to explore the use of BM sparing techniques among patients of carcinoma cervix. PATIENTS AND METHODS: Twenty patients of carcinoma cervix FIGO Stage IIIB treated with concurrent chemoradiotherapy were selected for this study. The external contour of bones was delineated on planning CT as a surrogate for BM. We generated three plans on a single patient:1. without BM as the dose constraint, namely N-IMRT plan; 2. with BM constraint, namely BMS-IMRT plan; 3. VMAT plan in which BM constraint was given. The dose volume histogram (DVH) for planning target volume (PTV) and organs at risk (OAR) were analyzed. BM parameters: V10, V20, V30, V40, mean, maximum and minimum dose were compared. Results: PTV coverage was comparable in all techniques. VMAT plans resulted in superior BM sparing compared with N-IMRT plan (P-<0.001) and BMS-IMRT plan (P-<0.001, 0.021 and 0.001 respectively for V20, V30 and V40). VMAT plans had better CI compared with BMS-IMRT (P-0.002) and N-IMRT (P-0.001) plans. CONCLUSION(S): Our study adds to the growing evidence that VMAT might be the preferred technique for patients with carcinoma of the cervix undergoing concurrent chemoradiotherapy, as it provides comparable target coverage and better sparing of bone marrow compared to IMRT.

Thalita, C., et al. (2021). "Physical therapy resources applied in the vaginal stenosis treatment after radiotherapy in cervical cancer patients: a systematic review and meta-analysis."
	
The AdventHealth Orlando, N., et al. (2021). Mother's Recorded Voice for Preterm Infants.
	The early birth of a premature baby can be a devastating and unplanned situation for parents. Often, their baby cannot be readily held; they can be very sick and fragile. Parents can feel helpless; bonding may be more difficult, parental control is superseded by medical necessity and parents can feel tremendous guilt whenever they are unable to be present at their baby's bedside. The investigators believe that giving parents an opportunity to provide comfort in the form of the mother's voice, pre-recorded and played to her baby, will improve her feeling about her baby in the NICU. The investigators hypothesize that playing the mother's recorded voice to her extremely preterm infant while in the incubator when she cannot be present will improve the depression, anxiety and stress as well as overall feeling about her baby. The investigators will assess the change in depression, anxiety and stress with the use of a validated tool (the DASS21), as a result of the intervention. The investigators will also assess the improvement of her feelings with a questionnaire () to be administered before and after the intervention. The investigators predict that her depression, anxiety and stress as well as positive feeling will increase after the intervention. The investigators also predict that the infant's vital signs will remain stable and/or improve when the recording is played.

The University of Texas Medical Branch, G. (2023). Retroperitoneal Tunneling Versus Dissection Technique During Sacrocolpopexy.
	No Results Available Procedure: Tunneling Technique during RA SCP|Procedure: Dissection Technique during RA SCP Operative Time (minutes)|POP-Q exam|Pelvic Floor Distress Inventory PFDI-20|Pelvic Floor Impact Questionnaire PFIQ-7|Pelvic Organ Prolapse/ Urinary Incontinence Sexual Questionnaire PISQ-12|Patient Global Impression of Improvement PGI-I|Decision Regret Scale (DRS)|Satisfaction with Decision Scale (SDS)|Clavien-Dindo classification for operative complication Female Not Applicable 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 23-0124 May 1, 2025

Thein Kyaw, Z., et al. (2022). "Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study." Investigational New Drugs 40(2): 290-299.
	Background: Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies.; Methods: This was a single-center, multi-arm phase Ib study utilizing a "basket type" expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible.; Results: Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks.; Conclusion: The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information.; Clinicaltrials: gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495 ). (© 2021. The Author(s).)

Thein, K. Z., et al. (2021). "Selinexor in combination with standard chemotherapy in patients with advanced or metastatic solid tumors." Experimental hematology & oncology 10(1): 59.
	Selinexor, an oral selective inhibitor of nuclear export (SINE), was demonstrated to hinder the DNA damage repair (DDR) system by reducing DDR proteins while enhancing the killing of cancer cells by DDR-based therapeutics in vivo studies. In this single-center, multi-arm phase 1b study, selinexor with carboplatin, doxorubicin and cyclophosphamide (DC), irinotecan with fluorouracil and folinic acid (FOLFIRI), irinotecan, and capecitabine and oxaliplatin (XELOX), were employed as separate parallel arms. Eligible patients have relapsed/ metastatic refractory solid tumors following standard therapy or addition of selinexor to systemic therapy was appropriate. Nineteen patients were treated in the 5 arms. Tumor types included were colorectal (n = 3), breast (n = 3), neuroendocrine (n = 2), ovarian (n = 2), and pancreas cancers (n = 2). All patients developed one treatment-related adverse events (TRAE). The most prevalent TRAE were thrombocytopenia (84%), nausea (68%), leukopenia (68%), neutropenia (63%), and fatigue (58%). The common grade 3/4 TRAE were neutropenia (42%), leukopenia (26%), and hyponatremia (21%). Three patients had dose-limiting toxicities (DLT) in 3 separate arms. Fourteen patients were evaluable for response. Although no patients achieved complete or partial response (CR or PR), seven patients attained stable disease (SD). Disease control rate (DCR) was 14%. The combination of oral selinexor with different standard chemotherapies showed limited clinical activity despite toxicity and DLT prevented further dose escalation. Optimizing supportive care, the utility of growth factors, and aggressive measures on antiemetics strategies remain tangible.Trial registration ClinicalTrials.gov Identifier: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495 ). Sponsor(s): Karyopharm Therapeutics.

Themistoklis, M., et al. (2021). "Surgical results in POP/UI surgery after using PVDF compared to other materials, a systematic review and meta-analysis."
	
Theocharis, P., et al. (2023). "The effect of metformin on bone mass of adolescent girls with polycystic ovary syndrome(PCOS): Systematic review."
	
Theofanakis, C., et al. (2020). "Minimizing Fertility-sparing Treatment for Low Volume Early Stage Cervical Cancer; Is Less the (R)Evolution?" Anticancer Research 40(7): 3651-3658.
	BACKGROUND/AIM: The aim of this study was to conduct a review on less radical fertility-sparing surgical treatment for early-stage cervical cancer. MATERIALS AND METHODS: We conducted a Medline search from 2014 to 2018 regarding less radical fertility-sparing techniques, such as simple trachelectomy or cervical conization, with pelvic lymphadenectomy. We also assessed the impact of the removal of the parametrium on the obstetric and oncologic outcome, in women who desire to preserve their fertility. RESULTS: We analyzed studies about cervical conization and simple trachelectomy, together with pelvic lymphadenectomy in early-stage cervical cancer. We also assessed the importance of parametrial involvement in reducing morbidity, without jeopardizing the oncologic outcome of these patients. Studies demonstrate that in tumors ≤2 cm, without lymphovascular Space Invasion and without evidence of parametrial involvement, a less radical fertility-sparing surgical approach could increase pregnancy rates and have a positive effect on the quality of life of these patients. CONCLUSION: Standard fertility-sparing treatment for early-stage cervical cancer is still radical trachelectomy with pelvic lymphadenectomy. However, studies suggest that the omission of parametrectomy is a feasible and safe option. Simple trachelectomy or cervical conization, both combined with pelvic lymphadenectomy are acceptable approaches in a selected group of patients with early-stage cervical cancer.

Therapeutics, M., et al. (2022). Upifitamab Rilsodotin Maintenance in Platinum-Sensitive Recurrent Ovarian Cancer (UP-NEXT).
	No Results Available Drug: Upifitimab rilsodotin|Other: Placebo Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1|Overall Survival (OS)|Progression-free Survival (PFS) as assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1|Adverse events (AEs) based on NCI CTCAE Version 5.0|Changes in Eastern Cooperative Oncology Group (ECOG) performance status|Objective Response Rate (ORR) as assessed by Investigator using RECIST Version 1.1|Number of participants using concomitant medications Female Phase 3 20 Industry|Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment XMT-1536-3 September 29, 2023

Thiel, P. and D. Rattray (2021). "Re: 'Prophylactic antibiotics for preventing genital tract infection in women undergoing surgical procedures for incomplete abortion: a systematic review and meta-analysis of randomised controlled trials'." BJOG : an international journal of obstetrics and gynaecology 128(13): 2211-2212.
	
Thiel Peter, S., et al. (2024). "Endometriosis and mental health: a population-based cohort study." American Journal of Obstetrics and Gynecology.
	Background: Endometriosis is a chronic gynecologic disorder that leads to considerable pain and a reduced quality of life. Although its physiological manifestations have been explored, its impact on mental health is less well defined. Existing studies of endometriosis and mental health were conducted within diverse healthcare landscapes with varying access to care and with a primary focus on surgically diagnosed endometriosis. A single-payer healthcare system offers a unique environment to investigate this association with fewer barriers to access care while considering the mode of endometriosis diagnosis.; Objective: Our objective was to assess the association between endometriosis and the risk for mental health conditions and to evaluate differences between patients diagnosed medically and those diagnosed surgically.; Study Design: A matched, population-based retrospective cohort study was conducted in Ontario and included patients aged 18 to 50 years with a first-time endometriosis diagnosis between January 1, 2010, and July 1, 2020. Endometriosis exposure was determined through either medical or surgical diagnostic criteria. A medical diagnosis was defined by the use of the corresponding International Classification of Disease diagnostic codes from outpatient and in-hospital visits, whereas a surgical diagnosis was identified through inpatient or same-day surgeries. Individuals with endometriosis were matched 1:2 on age, sex, and geography to unexposed individuals without a history of endometriosis. The primary outcome was the first occurrence of any mental health condition after an endometriosis diagnosis. Individuals with a mental health diagnosis in the 2 years before study entry were excluded. Cox regression models were used to generate hazard ratios with adjustment for hysterectomy, salpingo-oophorectomy, infertility, pregnancy history, qualifying surgery for study inclusion, immigration status, history of asthma, abnormal uterine bleeding, diabetes, fibroids, hypertension, irritable bowel disorder, migraines, and nulliparity.; Results: A total of 107,832 individuals were included, 35,944 with a diagnosis of endometriosis (29.5% medically diagnosed, 60.5% surgically diagnosed, and 10.0% medically diagnosed with surgical confirmation) and 71,888 unexposed individuals. Over the study period, the incidence rate was 105.3 mental health events per 1000 person-years in the endometriosis group and 66.5 mental health events per 1000 person-year among unexposed individuals. Relative to the unexposed individuals, the adjusted hazard ratio for a mental health diagnosis was 1.28 (95% confidence interval, 1.24-1.33) among patients with medically diagnosed endometriosis, 1.33 (95% confidence interval, 1.16-1.52) among surgically diagnosed patients, and 1.36 (95% confidence interval, 1.2-1.6) among those diagnosed medically with subsequent surgical confirmation. The risk for receiving a mental health diagnosis was highest in the first year after an endometriosis diagnosis and declined in subsequent years. The cumulative incidence of a severe mental health condition requiring hospital visits was 7.0% among patients with endometriosis and 4.6% among unexposed individuals (hazard ratio, 1.56; 95% confidence interval, 1.53-1.59).; Conclusion: Endometriosis, regardless of mode of diagnosis, is associated with a marginally increased risk for mental health conditions. The elevated risk, particularly evident in the years immediately following the diagnosis, underscores the need for proactive mental health screening among those newly diagnosed with endometriosis. Future research should investigate the potential benefits of mental health interventions for people with endometriosis with the aim of enhancing their overall quality of life. (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thimmaiah, N., et al. (2024). "Dosimetric Comparison of Isodose Surface Volume and Total Reference Air Kerma (TRAK) based Volume in Cervical Cancer Brachytherapy." Asian Pacific journal of cancer prevention : APJCP 25(2): 587-594.
	OBJECTIVE: We aim to compare TRAK & TPS based isodose volumes in cervical cancer brachytherapy and assess the feasibility, accuracy and potential future implications of TRAK in this regard and as a newer emerging tool to assess treatment intensity in cervical cancer brachytherapy. METHOD(S): one hundred patients with histologically proven squamous cell carcinoma of cervix uteri were assessed for brachytherapy (after completion of external radiation) and prospectively enrolled for the study. 60 Gy, 75 Gy, and 85 Gy isodose volumes were obtained from the TPS (VTPS) for 50, 25 & 25 patients with Manchester, Fletcher & interstitial implant respectively, receiving various fractionation schedules by Ir192 HDR remote after-loading system. Using the formula Vpred=4965(TRAK/dref)3/2+170(TRAK/dref)-1.5 the TRAK based isodose surface volumes (Vpred) were derived. Reference doses (dref) were calculated based on accumulated EBRT and brachytherapy doses. The two sets of volume were compared with respect to applicator type, standard, and optimised plan. Surrogate point A dose was also correlated. RESULT(S): VTPS - Vpred were 5.24 +/- 2.7%, all volumes being predicted within 10%. Correlation of TRAK vs VTPS60/ VTPS75/ VTPS85 showed R2 of 0.994, 0.987 and 0.971 respectively. There was no significant difference in predicted volumes with respect to applicator type. The surrogate point A showed mean volume and standard deviation of 7.44 +/- 13.4%, 17.63 +/- 16.38 and 3.5 +/- 0.95 for Manchester optimised, Fletcher optimised and standard plans respectively. TRAK with point A (R2=0.5632), bladder (R2=0.2015) and rectal doses (R2=0.121) yielded no correlation. CONCLUSION(S): Volumes calculated by TRAK correlate with TPS obtained volumes significantly and the formula predicting isodose surface volumes within 10% accuracy for ICBT applications and not for pure interstitial implants. However, TRAK fails to correlate with surrogate point A, bladder and rectal doses hence has questionable utility as a marker for biological response & treatment intensity.

Thomas, B., et al. (2020). "Support systems taking spouses into account in case of maternal postpartum depression: Review of international literature." Dispositifs d'accompagnement prenant en compte les conjoints en cas de depression du post-partum maternelle: Revue de la litterature internationale. 68(6): 288-302.
	(French) Introduction: De par sa frequence et ses nombreuses consequences, la depression du post-partum maternelle (DPPM) peut etre consideree comme une problematique de sante publique. Or, le facteur de bon pronostic le plus puissant semble etre le soutien social, et en particulier le soutien conjugal. Il faut donc etre attentif aux conjoints dans les soins que nous pouvons dispenser. Nous proposons donc de faire l'etat des lieux des dispositifs d'accompagnement prenant en compte les conjoints en cas de DPPM. Materiel et methodes: Nous avons realise une revue de la litterature en cherchant les etudes publiees sans limite temporelle dans les bases de donnees Pubmed, Cairn et Google Scholar. Les etudes selectionnees s'interessaient a des dispositifs d'accompagnement prenant en compte les conjoints dans le cas de depression maternelle durant la grossesse ou le post-partum, averee ou en prevention, et disposaient d'une evaluation de l'humeur maternelle et/ou de celle du conjoint. Resultats: Seize etudes ont ete incluses dans la revue de litterature. Les dispositifs ayant les resultats les plus probants semblent etre ceux qui incluent les conjoints lors d'un traitement curatif d'une DPPM deja installee. Peu de donnees existent concernant leur effet sur l'humeur paternelle. Conclusion: Des etudes centrees specifiquement sur les representations et vecus des conjoints confrontes a la DPPM nous semblent indispensables a realiser, dans le but de pouvoir imaginer des dispositifs d'accompagnement adaptes a l'ensemble des conjoints. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Thomas, T., et al. (2020). "Mindfulness and menopause- A review." Journal of Clinical and Diagnostic Research 14(7): QE01-QE03.
	Mind-body therapies hold several advantages from the viewpoint of security, fulfilment, implementation, and possible ancillary social and psychological health benefits. Side effects and risks of mind-body practice are generally nominal, implementation costs are little and most mind-body therapies can be performed by a broad range of populations, including overweight and sedentary menopausal women. The use of mind-body therapies for the alleviation of a menopausal symptoms is becoming increasingly common because of the perceived therapeutic benefits. The practice of mindfulness allows the participants to be aware of the present moment without concern for past or future consequences. Several researchers have discovered that being mindful may be helpful for menopausal women struggling with irritability, anxiety, and depression. The present study aimed at reviewing the literature which studies the impact of the mindfulness-based training on menopausal symptoms among women during their climacteric period. Many midlife women try out practices like relaxation techniques, breathing exercises, and yoga to help them get through these difficult times during their transitional period of life. Although these daily practices probably do not relieve symptoms such as hot flashes, they might improve overall wellbeing and help them sleep better. The literature was searched using databases such as CINAHL, Pub Med, Pro-Quest, and Google scholar. The search terms used were: menopause, menopausal symptoms, mindfulness, quality of life, and midlife transition. In India, the practice of mindfulness is not very well known among the menopausal women, so the aim of this review was to show a pathway to the primary health care workers like physicians, counsellors and the nurses, who can guide them about the practice of mindfulness thereby improving the quality of life.Copyright © 2020 Journal of Clinical and Diagnostic Research. All rights reserved.

Thomas Teresa, H., et al. (2023). "Testing the effects of the Strong Together self-advocacy serious game among women with advanced cancer: Protocol for the STRONG randomized clinical trial." Contemporary Clinical Trials 124: 107003.
	Background: Women with advanced cancer experience significant barriers to achieving high-quality care and maximizing their physical and emotional health. Our novel serious game, Strong Together, aims to teach women with advanced cancer self-advocacy skills needed to improve their symptom burden, quality of life, and patient-centered care.; Methods: This is a single-center, multi-site randomized clinical trial of the Strong Together intervention among 336 women within three months of an advanced breast or gynecologic cancer diagnosis. Randomization occurs to the 3-month Strong Together serious game or enhanced care as usual group. The aims are to: (1) evaluate the effects of the intervention on patient self-advocacy (primary outcome); (2) evaluate the effects of the intervention on quality of life, symptom burden, and patient-centered care (secondary outcomes); and (3) evaluate the behavioral and game mechanisms that influence the efficacy of the intervention.; Eligibility Criteria: female, age ≥ 18 years; diagnosis of advanced breast or gynecologic cancer within the past 3 months; Eastern Cooperative Oncology Group score of 0-2; English literacy; and ≥ 6-month life expectancy. Patient-reported outcome measures are collected at baseline, 3-months, and 6-months.; Conclusion: This protocol is the first large-scale intervention aimed at promoting self-advocacy in women with advanced cancer. Understanding the ability of serious games to impact patient outcomes provides critical information for researchers, clinicians, and stakeholders aiming to improve patient-centered care.; Trial Registration: NCT04813276.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Thompson, E. F., et al. (2022). "Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification." Modern Pathology 35(12): 1974-1982.
	We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.Copyright © 2022, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.

Thompson Emily, F., et al. (2022). "Significance of p53 and presence of differentiated vulvar intra-epithelial neoplasia (dVIN) at resection margin in early stage human papillomavirus-independent vulvar squamous cell carcinoma." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.
	Objective: Vulvar squamous cell carcinoma and in situ lesions can be stratified by human papillomavirus (HPV) and TP53 status into prognostic risk groups using p16 and p53 immunohistochemistry. We assessed the significance of vulvar squamous cell carcinoma resection margin positivity for either differentiated vulvar intra-epithelial neoplasia (dVIN) or abnormal p53 immunohistochemistry, and other pathologic variables, in a cohort of patients with HPV-independent (HPV-I) p53 abnormal (p53abn) vulvar squamous cell carcinomas.; Methods: Patients with stage I-II HPV-I p53abn vulvar squamous cell carcinoma with negative invasive margins who did not receive adjuvant radiation from a single institution were included. Tumors underwent margin reassessment using p53 immunohistochemistry. Cases were segregated into (1) morphologic dVIN at margin; or (2) abnormal p53 immunohistochemistry staining at margin without morphologic dVIN (p53abn immunohistochemistry); or (3) margins negative by morphology and p53 immunohistochemistry. Clinicopathologic/outcome data were collected.; Results: A total of 51 patients were evaluated: (1) 12 with dVIN on margin; (2) 12 with p53abn immunohistochemistry on margin without morphologic dVIN; and (3) 27 with margins negative for morphologic dVIN and p53abn immunohistochemistry. The recurrence rate for patients with dVIN or p53abn immunohistochemistry on the margin was equally high at 75% each, compared with 33% with margins negative for morphologic dVIN and p53abn immunohistochemistry (p=0.009). On multivariate analysis, positive in situ margins maintained an association with disease recurrence (p=0.03) whereas invasive margin distance (radial and deep), lymphovascular invasion, and tumor size did not.; Conclusions: Patients with stage I-II HPV-I vulvar squamous cell carcinoma with margins positive for either dVIN or p53abn immunohistochemistry without morphologic dVIN showed increased disease recurrence, regardless of invasive margin distance. These findings show that p53 immunohistochemistry is a useful adjunct for evaluating margin status in HPV-I vulvar squamous cell carcinoma and may support repeat excision for positive in situ margins (dVIN or p53abn immunohistochemistry).; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Thompson, G. R., et al. (2023). "Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial." Lancet (London, England) 401(10370): 49‐59.
	BACKGROUND: Rezafungin is a next‐generation, once‐a‐week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double‐blind, double‐dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30‐day all‐cause mortality for the US Food and Drug Administration (FDA), both with a target non‐inferiority margin of 20%, assessed in the modified intention‐to‐treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference ‐1·1% [95% CI ‐14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI ‐9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment‐emergent adverse event. The most common treatment‐emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non‐inferior to caspofungin for the primary endpoints of day‐14 global cure (EMA) and 30‐day all‐cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment‐emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.

Thompson, K. A. and A. M. Bardone-Cone (2021). "2019-nCOV distress and depressive, anxiety and OCD-type, and eating disorder symptoms among postpartum and control women." Archives of Women's Mental Health 24(4): 671-680.
	This study compared postpartum and control women on depressive, anxiety, and OCD-type symptoms, and eating disorder symptoms during the 2019-nCOV pandemic and evaluated if associations between 2019-nCOV distress and these mental health symptoms differed for postpartum compared to control women. A community sample of women, ages 18-39, who had either given birth in the past 12 months (n = 232) or had no pregnancy history (n = 137; controls), was recruited to complete an online survey about their depressive, anxiety, OCD, and eating disorder symptoms. Postpartum women reported greater OCD-type symptoms related to concerns about both contamination and responsibility for harm (ps < .05) compared to controls. After controlling for general stress and mental health history, the association between 2019-nCOV distress and OCD-type symptoms related to concerns about contamination was stronger among postpartum compared to control women (ps < .002). For all women, 2019-nCOV distress was positively related to general anxiety symptoms, total OCD-type symptoms, and OCD-type symptoms related to concerns about responsibility for harm after controlling for general stress and mental health history (ps < .03). Data are first to suggest postpartum women may be at elevated risk for OCD-type symptoms during 2019-nCOV pandemic, and pandemic distress is associated with anxiety and OCD-type symptoms among postpartum women more so than control women.

Thomson Zoe, O., et al. (2020). "Weight loss outcomes in premenopausal versus postmenopausal women during behavioral weight loss interventions: a systematic review and meta-analysis." Menopause (New York, N.Y.) 28(3): 337-346.
	Importance: Weight loss may be difficult for young women with obesity to achieve due to competing priorities (caring for children and/or full-time work), limiting their ability to engage in weight loss interventions. Older or postmenopausal women may also face challenges to weight loss such as caring responsibilities and menopause. Menopausal status may reflect differences in weight loss.; Objective: This study compared changes in weight, fat mass, and lean mass in premenopausal versus postmenopausal women in dietary weight loss trials.; Evidence Review: We reviewed publications from January 2000 to June 2020 evaluating a weight loss intervention with a dietary component, with or without exercise, and reporting weight loss of premenopausal and postmenopausal women. Where available, data on mean change from baseline for weight, fat mass, and lean mass of premenopausal and postmenopausal groups were entered into Review Manger for meta-analyses. Differences between menopausal groups were compared in subgroups of studies for intervention characteristics (diet-only vs diet and exercise; dietary modification vs meal replacement; < 24 wks vs ≥24 wks duration).; Findings: Seven publications (10 interventions, n = 791) were included; three single-arm trials, two randomized controlled trials, and two comparative effectiveness trials. In meta-analyses, there were no statistically significant differences between premenopausal and postmenopausal women (shown as premenopausal minus postmenopausal) for change in weight (0.58 [95% confidence interval -0.12 to 1.28] kg, n = 7 interventions), fat mass (0.73 [-0.25 to 1.70] kg, n = 6 interventions), or lean mass (-0.5 6[-1.48 to 0.36] kg, n = 4 interventions). However, a statistically significant subgroup difference was observed for fat mass change between menopausal groups (premenopausal minus postmenopausal) when comparing diet-only (1.28 [0.23 to 2.33] kg, n = 4 interventions) versus diet and exercise interventions (-0.09 [-0.51 to 0.32]kg, n = 2 interventions). No differences were shown in any other subgroups.; Conclusions and Relevance: This review provides some evidence to suggest weight loss interventions may not need to be tailored to women's menopausal status. However, given the small number of studies, short intervention duration in most publications (≤ 6 mo) and unclear retention rates in premenopausal versus postmenopausal groups of some publications, menopausal group differences should be examined in existing and future trials where the appropriate data have been collected.; Competing Interests: Financial disclosure/conflicts of interest: AS owns 50% of the shares in Zuman International Pty Ltd, which receives royalties for books she has written about adult weight management, and payments for presentations at industry conferences. She has also received presentation fees and travel reimbursements from Eli Lilly and Co, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, the Pharmaceutical Society of Australia, and Metagenics, and she served on the Nestlé Health Science Optifast VLCD advisory board from 2016 to 2018. ZT is supported by a Research Training Program Scholarship. JK is supported through a Griffith University Postdoctoral Research Fellowship. AS is supported via the National Health and Medical Research Council (NHMRC) of Australia with a Senior Research Fellowship (1135897). (Copyright © 2020 by The North American Menopause Society.)

Thornburgh, S. and J. Gaskins Audrey (2022). "B vitamins, polycystic ovary syndrome, and fertility." Current opinion in endocrinology, diabetes, and obesity 29(6): 554-559.
	Purpose of Review: This review provides a general overview of the literature on B vitamins and fertility, as well as summarizes the evidence concerning B vitamin supplementation and fertility among polycystic ovary syndrome (PCOS) women.; Recent Findings: Studies among women conceiving with and without medical assistance provide strong evidence for a beneficial effect of B vitamins, particularly folate and vitamin B12, on fecundability and fertility. Moreover, recent work suggests that effects may be even more pronounced among women with menstrual cycle dysfunction (a common symptom of PCOS). Among PCOS women, intervention studies have demonstrated that folic acid supplementation may reduce homocysteine levels, potentially improve women's metabolic profiles, and possibly ameliorate some hallmark features of PCOS. Although none of these intervention studies have included fertility endpoints, it is possible that by reducing homocysteine levels (or other clinical/biochemical features) in PCOS women, there may be a downstream improvement in fertility outcomes.; Summary: There is growing evidence folate (and possibly vitamin B12) supplementation may be beneficial to fertility in women. Although most studies have not exclusively focused on women with PCOS, there is biological plausibility and some evidence that B vitamin supplementation may be even more important for improving reproductive health outcomes in PCOS women. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Thurman, A., et al. (2023). "Pharmacokinetics, safety and preliminary pharmacodynamic evaluation of DARE-VVA1: a soft gelatin capsule containing tamoxifen for the treatment of vulvovaginal atrophy." Climacteric : the journal of the International Menopause Society 26(5): 479-488.
	Objective: This study aimed to measure safety, systemic pharmacokinetics and preliminary efficacy of a vaginal tamoxifen capsule (DARE-VVA1) among postmenopausal women with moderate-to-severe vulvovaginal atrophy.; Methods: This was a randomized, placebo-controlled, double-blind, phase 1/2 study of DARE-VVA1, in four doses (1, 5, 10 and 20 mg).; Results: Seventeen women were enrolled and 14 completed the 8-week treatment. DARE-VVA1 was safe. All adverse events were of mild or moderate severity and distributed similarly among active and placebo groups. Plasma tamoxifen concentrations were highest among women using DARE-VVA1 20 mg, but the maximum mean (standard deviation) plasma tamoxifen concentrations on day 1 (2.66 ± 0.85 ng/ml) and day 56 (5.69 ± 1.87 ng/ml) were <14% of those measured after one oral tamoxifen dose. Active study product users had significant decreases from pre-treatment baseline in vaginal pH and proportion of vaginal parabasal cells ( p = 0.04 for both endpoints), with women randomized to the 10 mg or 20 mg dose experiencing the largest treatment impact. The severity of vaginal dryness and dyspareunia decreased significantly from baseline with active study product use ( p = 0.02 for both endpoints).; Conclusions: DARE-VVA1 is safe and results in minimal systemic exposure to tamoxifen. Preliminary efficacy data support further development of this product.

Thurman, A., et al. (2023). "A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal RinGSM) over 12 weeks in healthy postmenopausal women." Menopause (New York, N.Y.) 30(9): 940-946.
	Objectives: The exploratory objectives of this study were to evaluate the usability and acceptability and to conduct a preliminary evaluation of the efficacy of DARE-HRT1. DARE-HRT1 is an intravaginal ring (IVR) that releases 17β2-estradiol (E2) with progesterone (P4) over 28 days. It is the first combination E2 and P4 IVR being developed for the treatment of vasomotor symptoms (VMS) in healthy postmenopausal women with an intact uterus.; Methods: This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d). They used the assigned IVR for three 28-day cycles, inserting a new IVR monthly. Preliminary genitourinary syndrome of menopause (GSM) treatment efficacy was estimated by measuring changes from baseline in vaginal pH, vaginal maturation index (VMI), and changes in the severity of GSM symptoms. Preliminary systemic VMS efficacy was measured by changes in responses to the Menopause-Specific Quality of Life (MENQOL) questionnaire. Acceptability was assessed by product experience surveys.; Results: Preliminary local GSM treatment efficacy was supported by significant decreases in vaginal pH and % parabasal cells, and significant increases in the overall VMI and % superficial cells for both IVR groups (all P values <0.01). Preliminary VMS efficacy was supported by significant decreases in all domains of the MENQOL questionnaire from baseline for both dosing groups (all P values <0.01).; Conclusions: Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.; Competing Interests: Financial disclosure/conflicts of interest: A.T., J.H., C.M., and D.F. are current employees of Daré Bioscience. N.Z. is a former employee of Daré Bioscience. M.L.H. and B.S. received funding from Daré Bioscience for activities directly related to conduct of the clinical trial described herein. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

Thurman, A., et al. (2023). "A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women." Menopause (New York, N.Y.) 30(8): 817-823.
	Objectives: Primary objectives were to evaluate the safety and systemic pharmacokinetics (PK) of DARE-HRT1, an intravaginal ring (IVR), which releases 17β2-Estradiol (E2) with progesterone (P4) for 28 days in healthy postmenopausal women.; Methods: This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women with an intact uterus. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d). They used the IVR for three 28-day cycles, inserting a new IVR monthly. Safety was measured by treatment emergent adverse events and changes in systemic laboratories and the endometrial bilayer width. Baseline adjusted plasma PK of E2, P4, and estrone (E1) was described.; Results: Both DARE-HRT1 IVR were safe. All treatment emergent adverse events were mild or moderate and were distributed similarly among IVR1 versus IVR2 users. Month 3 median maximum plasma ( Cmax ) P4 concentrations were 2.81 and 3.51 ng/mL and Cmax E2 was 42.95 and 77.27 pg/mL for IVR1 and IVR2 groups, respectively. Month 3 median steady state ( Css ) plasma P4 concentrations were 1.19 and 1.89 ng/mL, and Css E2 was 20.73 and 38.16 pg/mL for IVR1 and IVR2 users, respectively.; Conclusions: Both DARE-HRT1 IVRs were safe and released E2 in systemic concentrations, which were in the low, normal premenopausal range. Systemic P4 concentrations predict endometrial protection. Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.; Competing Interests: Financial disclosure/Conflicts of interest: A.T., J.H., C.M., and D.F. are current employees of Daré Bioscience. N.Z. is a former employee of Daré Bioscience. M.L.H. and B.S. received funding from Daré Bioscience for the conduct of this study. M.L.H. received a past travel grant from Giddeon Rickter and currently receives an educational grant from Organon. M.L.H. also is an owner of Embrace Fertility. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

Thurman, A. R., et al. (2024). "Pharmacokinetics, Safety and Preliminary Pharmacodynamic Evaluation of DARE-VVA1: A Soft Gelatin Vaginal Tamoxifen Capsule for the Treatment of Vulvovaginal Atrophy." Journal of Neurosurgical Anesthesiology 36(1): 1301.
	Objective: Safety, systemic pharmacokinetics (PK) and preliminary assessment of treatment efficacy were measured among healthy postmenopausal women with moderate-to-severe vulvovaginal atrophy (VVA) in this first-in-woman study of DAREVVA1, a soft gelatin vaginal tamoxifen capsule. Design(s): This was a randomized, placebo-controlled, double-blind, study of DARE-VVA1, vaginal tamoxifen, in 4 doses (1 mg, 5 mg, 10 mg and 20 mg). Women used study product daily for 14 days and then twice weekly for 6 weeks. Result(s): We screened 45 women and enrolled 17 (mean age 61 years); 14 women completed the study at two Australian clinical sites. Three participants (1 placebo, 2 in 5 mg group) were discontinued due to protocol violations. All treatment emergent adverse events (TEAEs) were mild or moderate in severity and were similarly distributed between active and placebo dosing groups. Endometrial thickness measurements were normal at baseline and end of treatment, with all <4.0 mm. Systemic tamoxifen and metabolite concentrations were highest among 20 mg users, but maximum mean (SD) plasma tamoxifen concentrations (Cmax) on day 1 (2.66 +/-0.85 ng/mL) and day 56 (5.69 +/-1.87 ng/mL) were <14% of Cmax measured after a single oral tamoxifen (20 mg) dose (40 ng/mL) (Table 1). Similarly, the first metabolite of tamoxifen, N-desmethyl tamoxifen (NDT) had mean (SD) Cmax plasma concentrations on day 1 (0.20 +/-0.17 ng/mL) and day 56 (8.13 +/-2.90 ng/mL), which were <2% of that steady state NDT concentrations (353 ng/mL) with oral tamoxifen use. Plasma tamoxifen concentrations were negatively correlated with vaginal pH (R = -0.51, p<0.01) and % vaginal parabasal cells (R = -0.53, p<0.01), and were positively correlated with % vaginal superficial cells (R = 0.45, p<0.01), % vaginal intermediate cells (R = 0.45, p<0.01) and total VMI (R = 0.62, p<0.01). Women reported vaginal dryness or dyspareunia as their most bothersome genitourinary symptom at baseline. The severity of these symptoms decreased significantly with active study product use (p = 0.02 for both), while placebo users had no significant changes in the severity of these symptoms (p values 0.17, 0.33 vaginal dryness and dyspareunia respectively). Conclusion(s): These data support that DARE-VVA1 is safe and results in minimal systemic exposure to tamoxifen or its metabolites compared to orally administered tamoxifen. Preliminary efficacy data support the clinical development of DARE-VVA1 to effectively lower vaginal pH and improve VMI and treat bothersome genitourinary symptoms.

Thurman, A. R., et al. (2024). "A Phase 1/2, Open-label, Parallel Group Study to Evaluate the Preliminary Efficacy and Usability DARE-HRT1 (80 mug Estradiol/4 mg Progesterone and 160 mug Estradiol/8 mg Progesterone Intravaginal Rings) Over 12 Weeks in Healthy Postmenopausal Women." Journal of Neurosurgical Anesthesiology 36(1): 1300-1301.
	Objective: The exploratory objectives of this study were to evaluate the usability and preliminary efficacy of DARE- HRT1, an intravaginal ring (IVR) which releases 17beta2- estradiol (E2) with progesterone (P4) over 28 days. Design(s): DARE-HRT1-002 was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women (median age 59 years), conducted at two sites in Australia. The study was approved by the ethics committee at each study site and registered at ClinicalTrials.gov (NCT05367973). Women were randomized (1:1) to DARE-HRT1-IVR1 (E2 80 mug/day with P4 4 mg/day) (n=11) or DARE-HRT1-IVR2 (E2 160 mug/day with P4 8 mg/day) (n=10). They used the assigned IVR for three 28-day cycles. Preliminary local vulvovaginal atrophy (VVA) treatment efficacy was estimated by measuring changes from baseline in vaginal pH, vaginal maturation index (VMI) and patient-reported severity of genitourinary VVA symptoms. Preliminary systemic vasomotor symptom (VMS) efficacy was measured by changes in responses to the menopause quality of life (MENQOL) questionnaire. Acceptability was assessed by product experience surveys. Result(s): Twenty-one participants were randomized and 19 women completed all study visits. Table 1 demonstrates significant improvement in vaginal pH, VMI and vaginal cytology with use of either DARE-HRT IVR. At baseline, 14 of 21 participants indicated that vaginal dryness was their most bothersome genitourinary symptom (MBS). Among this subset (8 from IVR1 cohort, 6 from IVR2 cohort), their median (interquartile range, IQR) reported vaginal dryness severity score was 2.0 (1, 3) at baseline and decreased to median (IQR) of 0 (0, 0) by end of treatment (EOT) with their respective IVRs (p < 0.01). These 14 women also had a significant decrease in dyspareunia severity from a median (IQR) of 1 (0, 2) at baseline to a median (IQR) of 0 (0, 0) at EOT (p<0.01). There were significant decreases from baseline, indicating improvement in all MENQOL domains, for both DARE-HRT1 IVRs (all p values<0.01), with the largest improvement in the MENQOL sexual domain. Based on MENQOL responses, the most commonly reported and most severe VMS at baseline was night sweats. With use of DARE-HRT1 IVR1, there was significant improvement in hot flashes and night sweats (p values 0.02 and 0.01 respectively), while there were no significant changes in sweating (p = 0.28) as 6/11 IVR1 users did not complain of this symptom at baseline. Among DARE-HRT1 IVR2 users, there was significant improvement in the severity of hot flashes, night sweats and sweating (all p values< 0.03). Most women agreed or strongly agreed that the study product was comfortable to wear, convenient to use and worked with their lifestyle. Most women reported that they were likely or very likely to use an IVR for treatment of women's health and other health conditions. Conclusion(s): This combination E2 and P4 IVR was acceptable and demonstrated preliminary efficacy for VMS and VVA treatment.

Thurston, R. C., et al. (2021). "Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN." Journal of the American Heart Association 10(3): e017416.
	Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women's Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in-person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1-5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow-up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow-up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05-2.17], P=0.03; 1-5 days: HR [95% CI], 1.02 [0.75-1.39], P=0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33-2.35], P<0.0001, multivariable). Conclusions Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female-specific CVD risk factor.

Thurston, R. C. and Y. Chang (2022). "Menopausal vasomotor symptoms and adiponectin among midlife women." Menopause (New York, N.Y.) 29(10): 1145-1149.
	OBJECTIVE: Vasomotor symptoms (VMS) are prevalent symptoms that can have a negative impact on quality of life. VMS have also been linked to cardiovascular disease risk, yet the mechanisms underlying these associations have not been elucidated. Some initial works link VMS to adverse adipokine profiles or cytokines produced by adipose tissue. However, results are not entirely consistent and are based entirely on self-report VMS, which is influenced by a range of memory and reporting biases. The aim of this work was to test whether physiologically assessed VMS are associated with lower adiponectin, the most abundant adipokine in the body, controlling for confounding factors. We also consider whether adiponectin explains previously documented relationships between VMS and carotid atherosclerosis. METHODS: A total of 300 peri- and postmenopausal nonsmoking women aged 40 to 60 years enrolled in the MsHeart study comprised the analytic sample. Women were free of hormone therapy or other medications impacting VMS, insulin-dependent diabetes, and cardiovascular disease. Participants underwent ambulatory physiologic VMS monitoring, physical measures, a carotid ultrasound, and fasting phlebotomy. RESULTS: More frequent physiologically assessed VMS were associated with lower adiponectin ( B [SE] = -0.081 [0.028], P = 0.004; or 0.081 lower μg/mL in adiponectin for each additional VMS over 24 hours), controlling for age, race/ethnicity, education, insulin resistance, and waist circumference. Associations were not explained by endogenous estradiol. Adiponectin did not explain associations between VMS and carotid atherosclerosis. CONCLUSIONS: Physiologic VMS were associated with lower adiponectin after considering potential confounders. The role of adipokines in VMS and in links between VMS and health warrants further attention.

Tiago, M., et al. (2024). "Effectiveness and safety of Cimicifuga racemosa and blackberry compared to soy isoflavone for the treatment of climacteric symptoms: a review of systematic reviews."
	
Tian, C., et al. (2022). "A Novel CDK4/6 and PARP Dual Inhibitor ZC-22 Effectively Suppresses Tumor Growth and Improves the Response to Cisplatin Treatment in Breast and Ovarian Cancer." International Journal of Molecular Sciences 23(5).
	In recent years, three PARP inhibitors and three CDK4/6 inhibitors have been approved by the FDA for the treatment of recurrent ovarian cancer and advanced ER-positive breast cancer, respectively. However, the clinical benefits of the PARPi or CDK4/6i monotherapy are not as satisfied as expected and benefit only a fraction of patients. Current studies have shown therapeutic synergy for combinations of PARPi and CDK4/6i in breast and ovarian cancers with homologous recombination (HR) proficiency, which represents a new synthetic lethal strategy for treatment of these cancers regardless HR status. Thus, any compounds or strategies that can combine PARP and CDK4/6 inhibition will likely have great potential in improving clinic outcomes and in benefiting more patients. In this study, we developed a novel compound, ZC-22, that effectively inhibited both PARP and CDK4/6. This dual-targeting compound significantly inhibited breast and ovarian cancer cells by inducing cell cycle arrest and severe DNA damage both in vitro and in vivo. Interestingly, the efficacy of ZC-22 is even higher than the combination of PARPi Olaparib and CDK4/6i Abemaciclib in most breast and ovarian cancer cells, suggesting that it may be an effective alternative for the PARPi and CDK4/6i combination therapy. Moreover, ZC-22 sensitized breast and ovarian cancer cells to cisplatin treatment, a widely used chemotherapeutic agent. Altogether, our study has demonstrated the potency of a novel CDK4/6 and PARP dual inhibitor, which can potentially be developed into a monotherapy or combinatorial therapy with cisplatin for breast and ovarian cancer patients with HR proficiency.

Tian, D., et al. (2023). "A Comparative Study on the Clinical Efficacy of Simple Transobturator Midurethal Sling and Posterior Pelvic Floor Reconstruction." Medicina (Kaunas, Lithuania) 59(1).
	Background and Objectives: The purpose of this study was to compare the complications, success rate and satisfaction of pelvic floor reconstruction after transobturator midurethral sling (TOT) and TOT combined with pelvic floor reconstruction in the treatment of female stress urinary incontinence. To explore the pathogenesis of stress urinary incontinence after pelvic floor stress injury and improve the surgical treatment strategy. Material(s) and Method(s): From 15 August 2018 to 24 February 2022, patients diagnosed with stress urinary incontinence (SUI) and secondary prolapse of the anterior pelvis were selected to receive surgically. Participants were followed up and evaluated at 2 months, 6 months and 1 year after treatment. According to the patient's chief complaint, the patient can urinate automatically without incontinence. The number of urinary incontinence and urine leakage was significantly reduced compared with those before operation. Urinary incontinence symptoms did not improve or worsen as ineffective, observing the efficacy and complications. Result(s): We included 191 patients in the TOT group and 151 patients in the pelvic floor reconstruction group after TOT was combined. The operation time and hospital stay in the TOT group were short, but the TOT group needed a second operation to treat recurrent SUI. Perioperative complications were mostly dysuria, and the incidence of postoperative complications in the group of TOT combined with pelvic floor reconstruction was low. The complete success rate and effective rate of pelvic floor reconstruction after TOT in the merger group were significantly higher than those in the TOT group, and the patient satisfaction and complete success rate were also higher. Conclusion(s): TOT combined with posterior pelvic floor reconstruction has a definite short-term effect on patients with SUI and anterior pelvic secondary prolapse. The operation design should pay attention to the support of the posterior wall of the perineum to the bladder neck and the middle and proximal end of the urethra.

Tian, H., et al. (2023). The dose-response association between acupuncture sessions and acupuncture effects on dysmenorrhea: a systematic review and dose-response meta-analysis of randomized controlled trials.
	Background: Acupuncture is a common treatment for dysmenorrhea. However, there is still uncertainty regarding the efficacy of acupuncture for patients with dysmenorrhea and the dose-response relationship between acupuncture and dysmenorrhea. Objective

Tian, L., et al. (2022). "Increased blastomere number is associated with higher live birth rate in day 3 embryo transfer." BMC Pregnancy and Childbirth 22(1): 198.
	Purpose: To study the relationship between blastomere number and pregnancy outcomes of day 3 embryo transfers.; Methods: This retrospective cohort study included 2237 fresh single day 3 embryo transfer cycles from October 2013 to November 2020. Patients were divided into six groups according to the blastomere number on day 3: ≤ 6-cell (n = 100), 7-cell (n = 207), 8-cell (n = 1522), 9-cell (n = 187), 10-cell (n = 91) and ≥ 11-cell (n = 130). Generalized estimating equation analysis based on multivariate logistic regression model was performed to adjust for potential confounders.; Results: The live birth rate (LBR) was 19.0%, 27.1%, 38.9%, 32.1%, 44.0% and 53.8% for the ≤ 6-cell, 7-cell, 8-cell, 9-cell, 10-cell and ≥ 11-cell groups, respectively (P < 0.001). Specifically, the ≤ 6-cell group was associated with reduced LBR compared with the 8-cell group (aOR 0.50, 95% CI 0.29-0.86; P = 0.013). Conversely, the odds of live birth were significantly increased in patients transferred with 10-cell embryos (aOR 1.62, 95% CI 1.03-2.53; P = 0.035) and ≥ 11-cell embryos (aOR 2.14, 95% CI 1.47-3.11; P < 0.001) when using the 8-cell embryo group as reference. Similar trends were also observed in the rates of positive hCG test and clinical pregnancy, while no significant differences were detected in miscarriage risk.; Conclusion: Increased blastomere number was associated with higher LBR in fresh single day 3 embryo transfer cycles. This finding questions the consensus on the reduced developmental potential of fast-cleaving embryos. Further large prospective studies are warranted for confirmation. (© 2022. The Author(s).)

Tian, Q., et al. (2022). "Effects of anemia during the third trimester of pregnancy on postpartum depression and pregnancy outcomes in pregnant women older than 35 years: a retrospective cohort study." Annals of Palliative Medicine 11(3): 1048-1057.
	Background: There is no study on the impact of anemia on postpartum depression and outcomes in mothers older than 35 years, which makes the nursing of these pregnant women with anemia more difficult.; Methods: We retrospectively collected the demographic and clinical characteristics of pregnant women older than 35 years at conception between August 2014 and December 2019. Hemoglobin less than 110 g/L was defined as anemia. Postpartum depression was assessed according to Edinburgh Postnatal Depression Scale. A subgroup analysis was performed by dividing anemia into mild anemia or moderate and severe anemia. All participants were followed up for at least 3 months postpartum and their pregnancy outcomes were recorded. The existence of postpartum depression was evaluated at 4 weeks postpartum. The risk factors of anemia during the third trimester of pregnancy and the impacts of anemia on postpartum depression and pregnancy outcomes were analyzed using multivariable logistic regression analysis.; Results: A total of 519 pregnant older than 35 years women were included in this study, including 281 without anemia and 238 with anemia. No significant difference was found in the incidence of postpartum depression between anemia and non-anemia groups (18.9% vs. 12.8%, P=0.057), while the anemia group had significantly higher incidence of preterm delivery, prolonged labor, and caesarean section. The subgroup analysis found that significantly pregnant women with older age in the moderate or severe anemia subgroup had postpartum depression than those in the mild anemia subgroup (23.2% vs. 12.5%, P=0.038). A higher rate of preterm delivery, prolonged labor, and caesarean section was recorded in the moderate or severe anemia subgroup (8.3% vs. 20.4%, P=0.012; 30.2% vs. 43.0%, P<0.001; 20.8% vs. 40.1%, P=0.002). Moderate or severe anemia, the presence of depression during the first trimester of pregnancy, unplanned pregnancy, and fewer parity were identified as risk factors of postpartum depression in pregnant women older than 35 years with anemia.; Conclusions: Anemia has significant impacts on pregnancy outcomes in pregnant women older than 35 years. Furthermore, moderate and severe anemia will significantly increase the incidence of postpartum depression, which should be corrected at an early stage to minimize its negative effects.

Tian, T., et al. (2022). "The Efficacy of the Yasmin[Ethinylestradiol-Drospirenone (0.03/3 mg)] Treatment for Postoperative Abortion: A Protocol of Meta-Analysis." Frontiers in Medicine 9: 746668.
	Background: Induced abortion is a universal phenomenon and about 25% of pregnancies in the world end in induced abortion. Induced abortion refers to the use of artificial or drug methods to terminate the pregnancy in the early stage of pregnancy, which is a remedy for failed contraception and accidental pregnancy. Induced abortion means surgical abortion. There are two commonly used methods: negative pressure suction abortion and forceps curettage for induced abortion. Abortion is invasive and it will cause great harm to women's reproductive function. Clinically, there are also cases of re-pregnancy within 3 months after abortion or even re-pregnancy without recovery of menstruation. To improve symptoms and reduce these complications, antibiotics, motherwort, and Yasmin[Ethinylestradiol-Drospirenone (0.03/3 mg)] are clinically used alone or in combination after induced abortion.; Methods: Data were collected from six databases, including three English databases of Cochrane Library, PubMed and Embase, and three Chinese databases of CNKI, Wanfang, and Weipu. The original indicators of vaginal bleeding, menstrual recovery time, bleeding time, endometrial thickness 21 days after surgery and so on were included, and the incidence of postoperative bleeding less than menstrual volume, menstrual re-fluid time ≤ 37 days, bleeding time ≤ 7 days, re-pregnancy without menstruation, re-pregnancy within 3 months after the operation, the total incidence of postoperative complications were based on the ratio of the number of events in the group to the total number of people in the group reported in the literature. Review Manager 5.4 software was downloaded from the Cochrane website to evaluate the quality of the literature and analyze the results using random or fixed-effects models. The outcome of index data is divided into two types, one is dichotomy, and the other is measurement data. The binary data is expressed by odds ratio (OR), and the measurement data is expressed by mean difference (MD), and the confidence interval of both is 95%.; Results: After completing this meta-analysis, the results will be available.; Conclusion: The results will provide reliable data basis for the value of Yasmin combined with antibiotics and Motherwort in postoperative induced abortion.; Prospero Registration Number: CRD42021246764.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Tian, Feng, Liao, Su, Li and Li.)

Tian, T., et al. (2021). "A meta-analysis of the efficacy of the Yasmin treatment for postoperative abortion."
	
Tian, X. and N. Yisen (2021). "Efficacy and safety of acupuncture alone or in combination with medication in patients with endometriosis: a systematic review and network meta-analysis."
	
Tian, Y., et al. (2020). "The effectiveness of iron supplementation for postpartum depression: A protocol for systematic review and meta-analysis." Medicine 99(50): e23603.
	Background: Postpartum depression (PPD) is one of the most common postpartum psychiatric disorders. The prevalence of PPD ranges from approximately 10% to 30%. In recent years, iron supplementation has emerged as potential means to treat PPD, and an increasing number of studies have been published to support the effectiveness of iron supplementation for PPD. we will conduct a comprehensive systematic review and meta-analysis to evaluate the evidence of randomized controlled trials for iron supplementation treatment of PPD.; Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Science, and Technology Journal Database, and Chinese Biomedical Literature Database will be searched from their inception of databases to December 31, 2020. Two reviewers will select articles, extract data and assess the risk of bias independently. Any disagreement will be resolved by discussion with the third reviewer. Review Manager 5.3 software will be used for data synthesis. The Cochrane risk of bias assessment tool will be used to assess the risk of bias.; Results: This study will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the effectiveness of iron supplementation for PPD.; Conclusions: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of iron supplementation for PPD, inform our understanding of the value of iron supplementation in improving PPD symptoms, and help clinicians to make better decisions regarding the appropriate role of iron supplementation as a part of prevention and treatment routines.; Study Registration Number: INPLASY2020110007.

Tian, Z., et al. (2023). "Effect of Surgically Induced Weight Loss on Pelvic Organ Prolapse: A Meta-analysis." Obesity surgery 33(11): 3402-3410.
	Introduction: Bariatric surgery alleviates certain aspects of pelvic floor disorder, but the effect on pelvic organ prolapse (POP) is unclear. To assess the effect of bariatric surgery on POP we conducted the present meta-analysis and firstly performed a subgroup analysis based on the duration of follow-up.; Methods: Four databases including PubMed, The Cochrane Library, Web of Science, and Embase were searched to identify relevant studies published before February 24, 2023. The main outcome was the prevalence and severity of POP symptoms before and after bariatric surgery. Then we assessed the heterogeneity, publication bias and performed subgroup analyses based on follow-up time, study quality and region.; Results: Eleven studies with a total of 696 participants met the inclusion criteria. The results showed that the prevalence of POP decreased after bariatric surgery (odds ratio[OR] = 2.29, 95% confidence interval[CI]: 1.05, 5.01; P = 0.04, I 2 = 78%), with significant differences observed both at 3-6 months (OR = 2.24, 95% CI: 1.25, 4.01; P = 0.007, I 2 = 59%) and 12 months (OR = 4.64, 95% CI: 2.83, 7.58; P < 0.0001, I 2 = 0%) of follow-up compared with pre-surgery. Pelvic Organ Prolapse Distress Inventory scores 6-item also decreased after bariatric surgery (mean difference [MD] = 2.11, 95% CI: 0.32, 3.89; P = 0.02, I 2 = 55%) with significant differences observed both at 3-6 months (MD = 3.72; 95% CI: [0.10, 7.34], P = 0.04, I 2 = 70%) and ≥ 12 months (MD = 3.24; 95% CI: [0.56, 5.91], P = 0.02, I 2 = 56%) of follow-up.; Conclusion: Bariatric surgery alleviated POP symptoms in women with obesity both during short-term (3-6 months) and long-term (≥ 12 months) follow-up. (© 2023. The Author(s).)

Tian, Z., et al. (2021). "Effects of bariatric surgery on patients with obesity and polycystic ovary syndrome: a meta-analysis." Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 17(8): 1399-1408.
	Background: Bariatric surgery is effective for polycystic ovary syndrome (PCOS), while the exact mechanism remains unclear.; Objectives: To assess the impact of bariatric surgery on PCOS patients and further explore the possible mechanism.; Setting: A meta-analysis.; Methods: We searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before November 2020.; Results: Twenty-one studies met our inclusion criteria, and we identified 552 patients with PCOS study. Results showed that the prevalence of preoperative PCOS, menstrual irregularity, hirsutism, type 2 diabetes (T2D), hypertension, infertility, and depression significantly decreased after bariatric surgery. Levels of total testosterone, fasting insulin, and luteinizing hormone (LH) decreased and estradiol increased, while levels of follicle-stimulating hormone (FSH) and LH/FSH did not show significant changes during the 3-month follow-up. There were decreases in testosterone and fasting insulin levels when the postoperative follow-up time was 6 months or ≥12 months. Levels of fasting blood glucose and triglycerides were significantly reduced after 6 months or ≥12 months of bariatric surgery. High-density lipoprotein (HDL) and sex hormone-binding globulin (SHBG) significantly improved ≥12 months after bariatric surgery.; Conclusion: Symptoms of PCOS and related complications are significantly alleviated after bariatric surgery. In addition, we found a significant improvement on anomalous secretion of gonadotropins, glucose metabolism, and lipid metabolism in patients with PCOS after bariatric surgery. (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Tilahune, A., et al. (2022). "The association between social support and antenatal depressive and anxiety symptoms among Australian women." European Psychiatry 65(Supplement 1): S211.
	Introduction: Antenatal depression and antenatal anxiety adversely affect several obstetric and foetal outcomes, and increase the rate of postnatal mental illness. Thus, to tackle these challenges the need for social support during pregnancy is vital. Objective(s): This study examined the association between domains of social support and antenatal depressive and anxiety symptoms among Australian women. Method(s): Our study used data obtained from the 1973-78 cohort of the Australian Longitudinal Study on Women's Health (ALSWH), focusing upon women who reported being pregnant (n=493). Depression and anxiety were assessed using the Center for Epidemiological Studies Depression (CES-D-10) scale, and the 9-item Goldberg Anxiety and Depression scale (GADS) respectively. The 19 item-Medical Outcomes Study Social Support index (MOSS) was used to assess social support. A binary logistic regression model was used to examine the associations between domains of social support and antenatal depressive and anxiety symptoms. Result(s): After adjusting for potential confounders, our study found that the odds of antenatal depressive symptoms was about four and threefold higher among pregnant women who reported low emotional/informational support (AOR=4.75; 95% CI: 1.45, 15.66; p=0.010) and low social support (overall support) (AOR: 3.26, 95%CI: 1.05, 10.10, p=0.040) respectively compared with their counterpart. In addition, the odds of antenatal anxiety symptoms was seven times higher among pregnant women who reported low affectionate support/positive social interaction (AOR=7.43; 95% CI: 1.75, 31.55; p=0.006). Conclusion(s): Low emotional support and low affectionate support have a significant association with antenatal depressive and anxiety symptoms respectively. As such, targeted screening of expectant women for social support is essential.

Tilak, M., et al. (2023). "Pelvic floor healing milestones after obstetric anal sphincter injury: a prospective case control feasibility study." International Urogynecology Journal 34(2): 553-561.
	Introduction and hypothesis: Severe perineal tears can predict bothersome pelvic floor disorders later in life. We have a poor understanding of pelvic floor changes during the third trimester and the first few postpartum months. We aimed to compare women with severe perineal trauma during childbirth with women who experienced minimal trauma, for condition-specific quality of life, sexual function, mental health and overall quality of life in the first 6 months postpartum. Method(s): We recruited primiparous women with third- or fourth-degree tears (obstetric anal sphincter injuries, OASIS) and age-matched controls with no tears or first-degree tears in the immediate postpartum period. Participants completed validated questionnaires at baseline, 2, 4 and 6 months postpartum. Mixed effects linear regression or quantile regression adjusted for baseline score were used to compare the groups as appropriate. Result(s): A total of 74 women completed at least one questionnaire (35 OASIS, 39 controls). Both groups had similar demographics. Women with OASIS tended to have worse Pelvic Floor Distress Index-40 scores at month 2; median scores were similar in the two groups by month 6. They also had significantly lower Female Sexual Function Index scores (mean difference: -6.1; 95% CI: -11.9, -0.2, p=0.043) at month 2. There were no mental health group differences and quality of life improved over time, mainly in the OASIS group. Six-month participant attrition rate was 52%. Conclusion(s): Women with OASIS encounter specific pelvic floor challenges during the first 6 months postpartum. Although our recruitment rate was high, the attrition rate was also high, demonstrating challenges with retention of postpartum women into longitudinal research.Copyright © 2022, The International Urogynecological Association.

Tilborghs, S. and S. De Wachter (2022). "Sacral neuromodulation for the treatment of overactive bladder: systematic review and future prospects." Expert Review of Medical Devices 19(2): 161-187.
	Introduction: Sacral Neuromodulation (SNM) is a minimally invasive treatment for OAB patients following failure of conventional interventions. Patient selection, lead placement, and testing technique are important pillars in optimizing success rates. Areas covered: A comprehensive literature search was conducted on 'sacral neuromodulation' and 'overactive bladder.' There was no date restriction, with the last search dated 31 May 2021. Patient selection, lead placement, test phases, safety, efficacy, and available devices are thoroughly discussedLastly, future perspectives will be presented with the anticipated trajectory of sacral neuromodulation over the next five years. Expert opinion/commentary: SNM has proved to be a safe and effective therapy on the short-, medium- and long-term without precluding any other treatment options. In all studies reviewed, no life threatening or major irreversible complications were presented. However, surgical re-intervention rates were high with a median of 33.2% (range: 8-34%) in studies with at least 24 months follow-up. No true consensus could be made regarding prognostic factors. However, optimized lead placement, consequent ideal motor thresholds, and the use of a curved stylet theoretically facilitates reaching maximal success with SNM. Test phase success rates increased to such a level that from a cost-effective point of view, single-stage implants could be considered. Abbreviations: OAB: overactive bladder; SNM: sacral neuromodulation; BoNT-A: Botulinum toxin A; PFM EMG: pelvic floor muscle electromyography; IPG: implantable pulse generator; PNE: percutaneous nerve evaluation; FSTLP: first-stage tined lead procedure; NLUTD: neurogenic lower urinary tract dysfunction; ITT: intention to threat; PPMC: per protocol modified completers; PPC: per protocol completers; AE: adverse event; MRI: magnetic resonance imaging; RCT: randomized controlled trial.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.

Tillett, A. L., et al. (2023). "Outcomes after vaginal versus robot assisted uterosacral ligament suspension for pelvic organ prolapse repair." American Journal of Obstetrics and Gynecology 228(3 Supplement): S848.
	Objectives: The primary objective of this study is to compare surgical outcomes for patients who underwent vaginal (VUSL) versus robot assisted (RUSL) uterosacral ligament suspension at the time of hysterectomy for pelvic organ prolapse repair. We aim to compare (1) characteristics of patients undergoing robotic versus vaginal uterosacral ligament suspension, (2) and prolapse repair failure based on composite of anatomic failure, subjective failure and/or retreatment. Material(s) and Method(s): This is a retrospective cohort study of all patients who underwent VUSL and RUSL at the time of hysterectomy from 2014-2020, inclusive. All eligible patients were identified. Data was extracted for patient demographics, clinical and surgical factors, and surgical outcomes using electronic medical records. The primary outcome was a composite of anatomic failure (Ba or Bp at or beyond hymen, C point that is 1/3 of TVL), subjective failure and/or conservative or surgical retreatment at 13-15 weeks post-operatively. If any of these criteria were met, the patient was noted to have a failed prolapse repair. Group comparisons were performed using student's t-test. A p value of <.05 was considered significant. Result(s): A total of 260 patients underwent VUSL and 192 patients underwent RUSL. The mean age was 72.1 +/- 9.0 for a vaginal surgical approach and 50.8 +/- 9.5 for a robotic surgical approach (p <0.0001). The mean BMI was 27.37 +/- 4.9 for a vaginal surgical approach and 30.4 +/- 6.2 for a robotic surgical approach (p <0.0001). Time spent under anesthesia for VUSL and RUSL were 188.1 +/- 38.3 and 162.3 +/- 47.7 respectively (p <0.0001). 63.3% of patients were available for follow up at the 13-15-week time point. The mean C point for the vaginal group was -5.7 +/- 2.1 versus the robotic group was -7.7 +/- 1.7 (p <0.0001). The mean Ba for the vaginal group was -1.7 +/- 1.2 versus the robotic group was -2.2 +/- 0.7 (p<0.0001). The mean Bp for the vaginal group was -2.2 +/- 1.1 versus the robotic group was -2.5 +/- 0.6 (p<0.009). Two patients in the vaginal group and zero patients in the robotic group reported bulge sensation. In both the patient groups, no patients required pessary or repeat surgery for prolapse. There were no patients with failed prolapse repair. Conclusion(s): Vaginal and robotic uterosacral ligament suspension are effective at addressing pelvic organ prolapse. The robotic group had more negative Ba, Bp and C points and no patients with bulge symptoms post-operatively. Patients undergoing the robotic approach spent less time in the operating room than the vaginal group. Compared to vaginal surgery, an experienced robotic team can improve operating room efficiency. Future studies are needed to evaluate long term surgical outcomes.Copyright © 2022

Tim, S. and A. I. Mazur-Bialy (2024). "Physiotherapy interventions in the treatment of pelvic floor dysfunctions after gynaecological oncology procedures: A systematic review." Journal of Gynecology Obstetrics and Human Reproduction 53(1): 102688.
	Cancer is one of the leading causes of death worldwide and a large percentage of cancer in women include gynaecological neoplasms. The aim of the review was to investigate the possibilities and effectiveness of physiotherapeutic techniques in the treatment of pelvic floor dysfunction after gynaecological oncology procedures. The review was performed in PubMed, Embase and PEDro databases. 5,561 articles were found, however only 11 met the inclusion criteria and were included in the review. To assess the risk of bias of included studies RoB-2 tool, ROBINS-1 were used. Ten studies were assessed as "low" and one study was asses as "moderate" risk. Studies have shown that the most common physiotherapeutic method described to treat pelvic floor dysfunction are pelvic floor muscle training, followed by biofeedback, electrostimulation, and behavioural training. Extracorporeal magnetic innervation is amongst the innovative method used in the treatment of UI amongst women who have overcome gynaecological cancer. On the other hand, in the treatment of sexual disorders, a vaginal dilator and pelvic floor training are used. Overall, pelvic floor training appears to be an effective technique in the treatment of pelvic floor dysfunction after the treatment of gynaecological malignancies. A small amount of research, a large variety of types of cancer, different methods of measuring results and small research trials make it difficult to accurately compare the results and draw appropriate conclusions.Copyright © 2023 The Author(s)

Timmermans, M., et al. (2023). "Impact of Adenomyosis and Endometriosis on Chronic Pelvic Pain after Niche Repair." Journal of Clinical Medicine 12(10).
	Chronic pelvic pain (CPP) is one of the main isthmocele symptoms, together with abnormal uterine bleeding and secondary infertility. When patients undergo a laparoscopic niche repair surgery, it is important to determine if they present associated pathologies, such as adenomyosis and/or endometriosis, which are also a cause of CPP. A retrospective study was performed on 31 patients with CPP undergoing a laparoscopic niche repair. The pre-operative ultrasound was analyzed to determine the presence of adenomyosis. Endometriosis was histologically diagnosed. CPP outcome was evaluated at early (3-6 months) and late (12 months) post-operative follow ups. In our population of 31 women presenting CPP, only six of them (19.4%) did not have any associated pathology. In the group of 25 patients with associated pathology, 10 (40%) had no benefit from the reconstructive surgery in terms of CPP at early follow-up (3-6 months) and 8 (32%) in the post-operative period at 12 months. Patients with CPP who undergo niche repair should be carefully selected as CPP does not seem to be a good indication for uterine scar repair in patients with concomitant adenomyosis and endometriosis.

Tineke, V., et al. (2022). "Quality of life after pelvic exenteration for vulval cancer."
	
Tingfeng, Z., et al. (2022). "Stem Cell Therapy For Premature Ovarian Insufficiency: A Single-Arm Meta-Analysis."
	
Tingxin, Z., et al. (2024). "Single-dose methotrexate versus two-dose methotrexate in the treatment of unruptured ectopic pregnancy: a systematic review and meta-analysis."
	
Tinker, A. V., et al. (2022). "Progression-free survival (PFS) and overall survival (OS) in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability-high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC) treated with dostarlimab in the GARNET study." Annals of Oncology 33(Supplement 7): S798-S799.
	Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy; and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Method(s): GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. Result(s): 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and >=6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached; estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported. [Formula presented] Conclusion(s): Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected. Clinical trial identification: NCT02715284. Editorial acknowledgement: Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study: GlaxoSmithKline. Funding(s): GlaxoSmithKline. Disclosure: A.V. Tinker: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Other: AstraZeneca, Eisai, GlaxoSmithKline. B. Pothuri: Financial Interests, Institutional, Funding: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK; Financial Interests, Personal, Other: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GSK, Merck, Sutro Biopharma, Tora, GOG Partners; Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Deciphera, Clovis Oncology, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray; Financial Interests, Personal, Leadership Role: GOG Partners, NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro; Financial Interests, Personal, Other: Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GlaxoSmithKline. R. Sabatier: Financial Interests, Institutional, Funding: AstraZeneca, Eisai; Financial Interests, Personal, Other: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche; Non-Financial Interests, Personal, Other: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Roche. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, GlaxoSmithKline; Financial Interests, Personal, Funding: GlaxoSmithKline, Genentech. S. Ghamande: Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Speaker's Bureau: GlaxoSmithKline; Financial Interests, Institutional, Funding Abbvie, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, Takeda. C. Mathews: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Deciphera, Moderna, GSK, Regeneron, Seattle Genetics; Financial Interests, Personal, Advisory Board: IMAB biopharma. D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana, Clovis, Elevar, Takeda, Toray, INXMED, SDP Oncology (BBI), Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics, Celsion Corp; Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Squibb Co, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc, inVentiv Health Clinical, Iovance, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, Clovis, SDP Oncology (BBI); Financial Interests, Personal, Other: Myriad Genetics, Tarveda. V. Boni: Financial Interests, Personal, Advisory Board: OncoArt, Guidepoint Global; Financial Interests, Personal, Speaker's Bureau: Solti; Financial Interests, Personal, Other: START, Loxo, IDEAYA Biosciences; Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Merus, Zenith Epigenetics, Genmab, AstraZeneca, Seattle Genetics, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, Boston Biomedical. A. Gravina: Financial Interests, Personal, Other: Gentili, Pfizer. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca; Non-Financial Interests, Advisory Role: Epsilogen; Non-Financial Interests, Other, Member of membership committee: ESGO; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. R. Miller: Financial Interests, Personal, Other: AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, Shionogi, AZD, GlaxoSmithKline; Financial Interests, Personal, Speaker's Bureau: AZD, Clovis Oncology, GSK, Roche. J. Pikiel: Financial Interests, Personal, Other: Amgen, Clovis Oncology, GlaxoSmithKline, Incyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen; Financial Interests, Institutional, Invited Speaker: Deciphera; Non-Financial Interests, Advisory Role: Ultimovacs, Apexigen. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. G. Antony: Financial Interests, Personal, Full or a t-time Employment: GlaxoSmithKline. S. Zildjian: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Zografos: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de Espana, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann -La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de Espana SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG.Copyright © 2022 European Society for Medical Oncology

Tiringer, D., et al. (2022). "Evaluation of quality of life in endometriosis patients before and after surgical treatment using the EHP30 questionnaire." BMC Women's Health 22(1): 538.
	Backround: Endometriosis is one of the most common gynecological illnesses causing extensive psychological, physical and social impact on patient's life and exerts negative effects on health-related quality of Life (HRQoL). However, the effects of surgery on the postoperative HRQoL in the different endometriosis subgroups have not been fully evaluated.; Methods: We performed a comparative retrospective study between 2014 and 2018 at the Medical University of Vienna, including all patients with surgically confirmed endometriosis who had completed the standardized Endometriosis Health Profile-30 (EHP-30) questionnaire 1 day after surgery (the questions refer to the 4 weeks preoperatively) and 6-10 weeks postoperatively.; Results: Compared to preoperative values, we found significant benefits, regarding postoperative conditions, in our study group (n = 115) in all five categories, "pain" (HR 0.78, p < 0.001); "self-determination" (HR 0.92, p < 0.001); "emotional health" (HR 0.83, p < 0.001);" social environment" (HR 0.67, p < 0.001); and "self-image" (HR 0.47, p < 0.001). Patients with only peritoneal endometriosis had the lowest preoperative clinical symptoms and there were no significant changes in any of the categories. In the subgroups deep infiltrating endometriosis (DIE) and DIE + ovarian endometrioma, surgical intervention results in a significantly greater improvement in all categories of EHP 30 compared to ovarian endometrioma without DIE or peritoneal endometriosis.; Conclusion: Our study shows, that especially women with DIE-with or without ovarian endometrioma-demonstrate a more pronounced benefit from surgical therapy compared to patients with peritoneal endometriosis or endometrioma without DIE. (© 2022. The Author(s).)

Tito, D. T., et al. (2021). "The Effects of Systemic Magnesium to Reduce Postoperative Pain Scores in Patients undergoing Hysterectomy: A Systematic Review and Meta-Analysis."
	
Tivizio, P., et al. (2023). "Digital technologies to support endometriosis : a systematic review."
	
Tobillo, R., et al. (2023). "Single Institution Experience of the Effect of Adjuvant Radiation on Outcomes for Patients with Uterine Carcinosarcoma." International journal of radiation oncology biology physics 117(2 Supplement): e549.
	Purpose/Objective(s): Uterine carcinosarcoma (UCS) is a rare but aggressive malignancy with poor outcomes. Due to its low incidence, there is no well-established optimal treatment. Standard treatment involves surgery and chemotherapy (CT) +/- adjuvant radiation therapy (RT). Our primary aim was to determine if patients who underwent adjuvant RT had improved distant metastasis free survival (DMFS) and locoregional recurrence free survival (LRRFS). Our secondary aim was to determine the effect of adjuvant RT on overall survival (OS). Materials/Methods: We performed a single institutional retrospective review of all patients with UCS who underwent primary surgical resection +/- CT and +/- RT between 2007 to 2021. Patients without at least 3 months of documented follow-up were excluded. We assessed DMFS, LRRFS, and OS between patients who did and did not receive adjuvant RT, consisting of vaginal brachytherapy (VBT), external beam radiation therapy (EBRT), or EBRT + VBT. Statistical analysis was performed with spreadsheet and statistical software. Result(s): Sixty-four patients underwent primary surgical resection for FIGO stage I-IV UCS. Sixty six percent (n = 42) had early stage, FIGO I-II disease and 34% (n = 22) had late stage, FIGO III-IV disease. Eleven percent (n = 7) underwent surgery alone, 28% (n = 18) underwent surgery + CT, 6% (n = 4) underwent surgery + adjuvant RT, and 55% (n = 35) underwent surgery + CT + RT. Most patients who underwent surgery + CT + EBRT + VBT (n = 9) had worse clinicopathologic features including late stage (56%), lymphovascular invasion positive (78%) disease with 50% or greater myometrial invasion (56%). EBRT doses ranged from 45-50.4 Gray (Gy) in 1.8 Gy per fraction. VBT doses ranged from 21-25 Gy in 3-5 fractions when delivered alone and 10-15 Gy in 2-3 fractions when delivered as a boost. Median DMFS was 20.3 months, median LRRFS was 22.6 months, median DFS was 19.4 months, and median OS was 24.7 months. Rate of distant metastasis appeared to drive rate of disease-free survival (Table 1). Patients who underwent adjuvant RT had improved median DMFS (71.5 vs. 11.3 months, p =.002), median LRRFS (71.5 vs 22.5 months, p =.002), and median OS (60.7 vs. 22.5 months, p =.002) compared to those who did not receive RT. Conclusion(s): Prognosis of patients with UCS remains poor; however, adjuvant RT delivered after CT may offer potential benefit in survival outcomes despite worse clinicopathologic features in these patients.Copyright © 2023

Tochigi, M., et al. (2024). "Lenvatinib plus Pembrolizumab Combination Therapy for Advanced or Recurrent Endometrial Cancer: A Single-Center, Retrospective Analysis." The Tohoku journal of experimental medicine 262(2): 85-95.
	A multi-kinase inhibitor, lenvatinib, plus an immune checkpoint inhibitor, pembrolizumab, became a viable therapeutic option for advanced or recurrent endometrial cancer in Japan by the end of 2021. The Japanese population has a relatively unique genetic background. Hence, the safety profile and effectiveness of lenvatinib plus pembrolizumab may differ between the Japanese and other populations. This single-center, retrospective study aimed to evaluate the treatment efficacy of lenvatinib plus pembrolizumab and the safety profile of the associated adverse events. The clinical records of 15 patients, who received lenvatinib plus pembrolizumab for advanced or recurrent endometrial cancer at the Tohoku University Hospital, were reviewed. Best overall response and disease control rates were 40.0% and 73.3%, respectively. Treatment was discontinued owing to disease progression and adverse events in six patients, respectively. As of the end of July 2023, treatment was ongoing in the remaining three patients. The median treatment and progression-free survival durations were 118 and 258 days, respectively. Relative dose intensity of lenvatinib was not positively associated with progression-free survival, neither during the first 4 weeks after treatment initiation nor during the entire treatment period. All patients experienced one or more adverse events, the most common of which were hypothyroidism (90%) and hypertension (83.3%). Among the 15 patients, 13 required lenvatinib dose reduction owing to adverse events. One patient developed grade 4 interstitial pneumonia requiring intensive care. Our results validate the short-term efficacy of lenvatinib plus pembrolizumab, and indicate that dose optimization of lenvatinib could be individualized without impairing efficacy.

Toczek, J., et al. (2021). "Endometriosis: New Perspective for the Diagnosis of Certain Cytokines in Women and Adolescent Girls, as Well as the Progression of Disease Outgrowth: A Systematic Review." International Journal of Environmental Research and Public Health 18(9).
	Endometriosis is a common chronic gynecological disorder that undoubtedly impacts on quality of life, and is one of the more complex and mysterious illnesses of our century, which is associated with the improper growth of endometrial tissue outside of the uterine cavity. This pathologically implanted tissue can be found most frequently in the minor pelvis, but also in the peritoneal cavity, and can affect many organs, leading to chronic pelvic pain syndrome, infertility, and dysmenorrhea. Endometrial tissue is a particularly dynamic tissue that has a direct impact on the progression of the disease, with altered immunity, as well as cytokine storms within the metaplastic endometriotic site, as possible key factors. Currently, diagnosis of this mysterious chronic illness relies on performing a laparoscopic procedure with tissue sampling. One of the most troublesome outcomes of this unintended progression is that we lack any specific, sensitive, non-invasive diagnostic tools. Currently, the vast majority of regime stewardship options rely on anti-contraceptive drugs, or other remedies that suppress the release of estrogen through the gonads-although in most clinical trials, endometriosis is a chronic progressive disorder that depends mostly on the high concentration of estrogen. Moreover, many specific trials have demonstrated that the eutopic endometrial cells in individuals with endometriosis remain much more resistant to the immunological annihilation process caused by certain elements of the immune system. Nevertheless, eutopic endometrial cells have the potential to similarly escalate the expression of aromatase receptors on the surface of the pathological cells, which in the final cascade cause an increase in the concentration of estrogen, as well as other inflammatory proteins that contribute to pathological outgrowth. Data reveal occurrence among first-degree relatives, suggesting that the specific cascade could be related to inherited as well as epigenetic (acquired) mechanisms. In women with the disease, confirmed by laparoscopic procedures, diagnosis of endometriosis can be established also via detection by gene polymorphism in the genes which are responsible for responsible for the detoxification phase of estrogen receptors and other immunomodulator components. A recent publication aims to reveal a new prospect for the non-invasive diagnosis, detection, and estimation of certain biomarkers for much more specific investigation of the disease's progression.

Toia, B., et al. (2022). "Functional outcomes of vaginal surgery for urethral extrusion of mid-urethral tape in women." International Urogynecology Journal 33(8): 2251-2256.
	Introduction and hypothesis: We aim to determine the presentation of and immediate and longer-term outcomes of vaginal surgical excision of urethral extrusion of mid-urethral tape (MUT). Method(s): We performed a retrospective analysis of all patients with urethral extrusion of MUT having vaginal surgical excision between 2007 and 2018. The MUT was removed either partially (via vaginal approach) or completely (via combined vaginal and laparoscopic approach). Functional outcomes and any re-interventions are described. Result(s): Thirty-four patients of median age 53 (range 34-82) years were identified. Preoperative symptomatic recurrent/persistent urinary incontinence was present in 29/34(85%) with 24/34(71%) women having recurrent/persistent stress urinary incontinence (SUI) or stress predominant mixed urinary incontinence (s-MUI) on urodynamics. Vaginal surgical excision was performed alone in 33/34(97%) women and in combination with laparoscopic removal of abdominopelvic MUT in 1/34(3%) woman. In the longer term vaginal/urethral pain resolved or improved in all 15/15(100%) patients presenting with this complaint whilst patient reported poor flow resolved in 8/9 (89%) women. Twenty-eight of 34 women (82%) had persistent/recurrent SUI or s-MUI following MUT excision. Twenty-four of 34 women (71%) had further SUI surgery with cure or improvement of SUI in 20/24 (83%) patients. Conclusion(s): The outcome of vaginal surgical excision of the MUT was cure or improvement of pain in 100% and resolution of poor flow in 89% women. Recurrent/persistent SUI or s-MUI was present in 82% following removal as compared to 71% women prior to removal. Of the 71% of women electing to have further surgery for recurrent/persistent SUI/s-MUI, 83% were dry or improved afterwards.Copyright © 2021, The International Urogynecological Association.

Tojima, Y., et al. (2022). "Effect of primary prophylaxis with pegfilgrastim in endometrial cancer patients treated with doxorubicin and cisplatin." Taiwanese Journal of Obstetrics & Gynecology 61(2): 265-269.
	Objective: Although the incidence of febrile neutropenia (FN) is relatively higher for doxorubicin and cisplatin combination regimen than for other regimens in endometrial cancer, evidence regarding the efficacy of pegfilgrastim in this regimen is lacking.; Materials and Methods: We retrospectively reviewed the data of 58 patients with endometrial cancer who were treated with doxorubicin plus cisplatin. The patients were divided into primary prophylaxis and non-prophylaxis groups. We compared the incidence of FN and neutropenia as well as the chemotherapy relative dose intensity (RDI) and usage of antibiotics between the groups.; Results: The rates of FN (8.0% vs. 34.8%) and grade 4 neutropenia (12.0% vs. 87.0%) were significantly lower in the primary prophylaxis group. Although there was no difference in the RDI between the groups, the primary prophylaxis group had a lower rate of antibiotic prescriptions.; Conclusion: Prophylaxis with pegfilgrastim efficiently prevented FN in patients treated with doxorubicin and cisplatin.; Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article. (Copyright © 2022. Published by Elsevier B.V.)

Tokumitsu, K., et al. (2020). "Prevalence of perinatal depression among Japanese women: a meta-analysis." Annals of General Psychiatry 19(1): 1-18.
	BACKGROUND: Perinatal depression is one of the important mental illnesses among women. However, not enough reviews have been done, and a certain consensus has not been obtained about the prevalence of perinatal depression among Japanese women. The purpose of our study is to reveal the reliable estimates about the prevalence of perinatal depression among Japanese women. METHOD: We searched two databases, PubMed and ICHUSHI, to identify studies published from January 1994 to December 2017 with data on the prevalence of antenatal or postnatal depression. Data were extracted from published reports. RESULTS: We reviewed 1317 abstracts, retrieved 301 articles and included 123 studies. The point prevalence of postpartum depression at 1 month was 14.3% incorporating 108,431 Japanese women. The period prevalence of depression at pregnancy was 14.0% in the second trimester and 16.3% in the third trimester. The period prevalence of postpartum depression was 15.1% within the first month, 11.6% in 1–3 months, 11.5% in 3–6 months and 11.5% in 6–12 months after birth. We also identified that compared with multiparas, primiparas was significantly associated with a higher prevalence of postpartum depression; the adjusted relative risk was 1.76. CONCLUSIONS: The prevalence of postpartum depression at 1 month after childbirth was found to be 14.3% among Japanese women. During pregnancy, the prevalence of depression increases as childbirth approaches, and the prevalence of depression was found to decrease in the postpartum period over time. In addition, we found that the prevalence of postpartum depression in primiparas was higher than that in multiparas. Hence, we suggest that healthcare professionals need to pay more attention to primiparas than multiparas regarding postpartum depression.

Tomasi Mariana, C., et al. (2022). "Symptoms and Surgical Technique of Bladder Endometriosis: A Systematic Review." Journal of Minimally Invasive Gynecology 29(12): 1294-1302.
	Objective: This systematic review aimed to review all the available evidence regarding bladder endometriosis (BE) surgical techniques, resolution of symptoms, and nodule size.; Data Sources: We conducted systematic searches in PubMed MEDLINE, Embase, Latin American and Caribbean Centre on Health Sciences Information, Cochrane Library, and Web of Science databases from inception to December 2021.; Methods of Study Selection: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the literature search yielded 1279 articles. Two reviewers independently screened abstracts and reviewed full-text articles to meet the eligibility criteria: women diagnosed as having BE, treated surgically to remove the BE nodule, and reported of the nodule size and/or symptoms after the surgery. We included 28 studies, which mainly were case reports and case series.; Tabulation, Integration, and Results: The following information was extracted from the included studies: author, country, publication year, study design, number of patients, age, surgery performed, follow-up time, operation time, nodule location, nodule size, and postsurgical symptoms. Patients' ages range from 26 to 44 years and most women were nulliparous. The BE nodule size ranged from 0.7 to 5.5 cm, and the most frequent location (63.57%) was the posterior wall. Dysuria was reported by 27.18% of women and generic lower urinary tract symptoms were reported by 27.95%. After surgery, the recurrence rate of urinary symptoms was 7.34%. Most studies performed a partial cystectomy to remove the nodule, showing that the disease affects the bladder mucosa frequently.; Conclusion: Surgical treatment with complete excision of BE lesion was shown to improve complaints of urinary symptoms in patients with BE. Given that most of the studies evaluated were descriptive, additional studies with a large sample population and a better level of evidence for this condition are needed. (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Tomassetti, C., et al. (2021). "The ultra-long study: a randomized controlled trial evaluating long-term GnRH downregulation prior to ART in women with endometriosis." Human reproduction (Oxford, England) 36(10): 2676-2686.
	STUDY QUESTION: Does ultra-long downregulation with a GnRH agonist (triptorelin depot) in previously operated patients with endometriosis improve the rate of clinical pregnancy with positive fetal heart beat (CPHB) in the subsequent initiated fresh ART cycle? SUMMARY ANSWER: Ultra-long downregulation with a GnRH agonist prior to ART did not improve the rate of CPHB in the subsequent fresh ART cycle in previously completely operated patients but the trial was underpowered due to early termination. WHAT IS KNOWN ALREADY: Administration of GnRH agonists for a period of 3-6 months prior to ART in women with endometriosis may increase the odds of clinical pregnancy. However, the quality of the studies on which this statement is based is questionable, so these findings need confirmation. STUDY DESIGN, SIZE, DURATION: A controlled, randomized, open label trial was performed between 1 June 2013 and 31 December 2016 (start and end of recruitment, respectively). Patients with prior complete laparoscopic treatment of any type or stage of endometriosis and an indication for ART were randomized (by a computer-generated allocation sequence) into two groups: the control group underwent ART stimulation in a classical long agonist protocol using preparation with oral contraceptives, the ultra-long group first underwent at least 3 months downregulation followed by a long agonist protocol for ART stimulation. The sample size was calculated to detect a superiority of the ultra-long downregulation protocol, based on the hypothesis that baseline CPHB rate in the control group of 20% would increase to 40% in the ultra-long group. For a power of 20% at a significance level of 5%, based on two-sided testing, including 5% of patients lost to follow-up, the necessary sample size was 172 patients (86 per group). PARTICIPANTS/MATERIALS, SETTING, METHODS: This trial was conducted at the Leuven University Fertility Center, a tertiary care center for endometriosis and infertility, and a total of 42 patients were randomized (21 in the control group and 21 in the ultra-long group). MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar in both groups. The primary outcome studied-CPHB after the initiated ART treatment-did not differ and was 25% (5/20) in the control group, and 20% (4/20) in the ultra-long group (P > 0.999; relative risk (RR) 1.25, 95% CI 0.41-3.88). Cumulative (fresh + associated frozen) CPHB rates were also similar in the control versus ultra-long group (8/20, 40% vs 6/20, 30%, P = 0.7411; RR = 1.33, 95% CI 0.57-3.19). When other secondary outcomes were compared with the ultra-long group, patients from the control group had a shorter duration of stimulation (mean 11.8 days (SD ± 2.4) versus 13.2 days (SD ± 1.5), P = 0.0373), a lower total dose of gonadotrophins used (mean 1793 IU/d (SD ± 787) vs 2329 (SD ± 680), P = 0.0154), and a higher serum estradiol concentration (ng/ml) at the end of ovarian stimulation on the day of ovulation triggering or cycle cancellation (mean1971 (SD ± 1495) vs 929 (± 548); P = 0.0326), suggesting a better ovarian response in the control group. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, nearly exclusively against ultra-long downregulation (even though patients were thoroughly informed of the potential benefits), the targeted sample size could not be achieved and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: Conditional power analysis revealed that the probability of confirming the study hypothesis if the study were completed would be low. We hypothesize that in patients with prior complete surgical treatment of endometriosis, the ultra-long protocol does not enhance ART-CPHB rates. Patient's concerns and preferences regarding possible side-effects, and delay of ART treatment start with the ultra-long protocol should be taken into account when considering this type of treatment in women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): C.T. was during 2 years funded by a grant from the Clin cal research Foundation of UZ Leuven (KOF) and during 2 years by the Research Foundation-Flanders (FWO grant number: 1700816N). C.T. reports grants from Clinical Research Foundation of the University Hospitals of Leuven (KOF), grants from Fund for Scientific Research Flanders (FWO), during the conduct of the study; grants, non-financial support and other from Merck SA, non-financial support and other from Gedeon Richter, non-financial support from Ferring Pharmaceuticals, outside the submitted work. T.D. is vice president and head of Global Medical Affairs Fertility, Research and Development, Merck KGaA, Darmstadt, Germany. He is also a professor in Reproductive Medicine and Biology at the Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven (University of Leuven), Belgium and an adjunct professor at the Department of Obstetrics and Gynecology in the University of Yale, New Haven, USA. Neither his corporate role nor his academic roles represent a conflict of interest with respect to the work done by him for this study. A.C. reports personal fees from Merck S.p.A., outside the submitted work. The other co-authors have no conflict of interest. TRIAL REGISTRATION NUMBER: UZ Leuven trial registry SS55300, EudraCT number 2013-000993-32, clinicaltrials.gov NCT02400801. TRIAL REGISTRATION DATE: Registration for EudraCT on 1 March 2013. DATE OF FIRST PATIENT’S ENROLMENT: 4 September 2013.

Tomassetti, C., et al. (2022). "The Ultra-Long Study: a Randomized Controlled Trial Evaluating Long-Term GnRH Downregulation Prior to ART in Women With Endometriosis." Obstetrical & gynecological survey 77(1): 32‐33.
	Although the adverse effect of endometriosis on pregnancy rate is well established, the impact of endometriosis on pregnancy rate after treatment with assisted reproductive technology (ART) remains unclear. There is evidence that the use of prolonged pituitary downregulation before ART in women with any degree of endometriosis increases the odds of clinical pregnancy significantly (up to 4-fold); however, this evidence is limited by potential methodology and publication bias.

Tomochika, S., et al. (2021). "Laparoscopic Sutureless Rectopexy Using a Fixation Device for Complete Rectal Prolapse." Surgical laparoscopy, endoscopy & percutaneous techniques 31(5): 608-612.
	BACKGROUND: Complete rectal prolapse (CRP) commonly affects the daily life of older people and has no established operative treatment approach. We describe our simple method of laparoscopic, sutureless rectopexy, involving rectal mobilization (along with its peritoneum bilaterally) and fixation to the sacral promontory using a fixation device. We also present an analysis of short-term outcomes in patients treated using this procedure. MATERIALS AND METHODS: We retrospectively evaluated 62 patients with CRP, who underwent a laparoscopic rectopexy via tack fixation, between 2004 and 2017. The peritoneum was widely attached near the site of peritoneal reflection, as in rectal cancer surgery. The hypogastric nerve was carefully detached from the front of the sacrum. Keeping the nerve intact, we lifted and mobilized the dissected rectum cranially towards the promontory, and the rectal peritoneum was affixed to the sacrum by applying 2 to 3 fixed tacks bilaterally, using a fixation device. RESULTS: The median age of the study group was 80 (10 to 91) years. All procedures were successful without serious intraoperative complications; only 1 patient required conversion to open surgery. Median values for operative duration, intraoperative blood loss, and postoperative period of hospitalization were 177 (125 to 441) minutes, 5 (0 to 275) mL, and 7 (3 to 17) days, respectively. Only 6 (9.7%) patients experienced recurrence during the follow-up period. CONCLUSION: Laparoscopic tacking rectopexy performed using a fixation device for repairing CRP is a simple, safe, and sutureless procedure with no severe complications or mortality.

Toneti Bruna, F., et al. (2020). "Benefits of Qigong as an integrative and complementary practice for health: a systematic review." Revista latino-americana de enfermagem 28: e3317.
	Objective: to analyze, in the literature, evidence about the benefits of the integrative and complementary practice of Qigong with regard to the health of adults and the elderly.; Method: a systematic review by searching for studies in the PubMed, CINAHL, LILACS, EMBASE and Cochrane Library databases. Randomized and non-randomized clinical trials were included; in Portuguese, English and Spanish; from 2008 to 2018. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses strategy was adopted, as well as the recommendation of the Cochrane Collaboration for assessing the risk of bias in the clinical trials analyzed.; Results: 28 studies were selected that indicated the benefit of the practice to the target audience, which can be used for numerous health conditions, such as: cancer; fibromyalgia; Parkinson's disease; Chronic Obstructive Pulmonary Disease; Burnout; stress; social isolation; chronic low back pain; cervical pain; buzz; osteoarthritis; fatigue; depression; and cardiovascular diseases. However, there was a great risk of bias in terms of the blinding of the research studies.; Conclusion: the practice of Qigong produces positive results on health, mainly in the medium and long term. This study contributes to the advancement in the use of integrative and complementary practices in nursing, since it brings together the scientific production in the area from the best research results available.

Tong, N., et al. (2023). "Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients." Frontiers in Oncology 13: 1035511.
	Objective: Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors. Materials/methods: Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses. Result(s): 261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS. Conclusion(s): In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.Copyright © 2023 Tong, Kumar, Gelowitz, Tinker, Holloway and Ko.

Tong, P., et al. (2019). "Traditional Chinese acupuncture and postpartum depression: A systematic review and meta-analysis." Journal of the Chinese Medical Association : JCMA 82(9): 719-726.
	Background: Acupuncture, a key component of traditional Chinese medicine, is a form of alternative medicine in which thin needles are inserted into the body commonly for pain relief. To date, the role of traditional Chinese acupuncture in mood disorders in the postpartum period is unclear. Thus, this study aimed to review the effectiveness of acupuncture in patients with postpartum depression (PPD).; Methods: We searched databases such as PUBMED, EMBASE, and Cochrane Controlled Trials Register until September 2018. Meta-analysis was performed using Comprehensive Meta-Analysis 2.0 software. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were calculated to evaluate the results of each comparison.; Results: A total of 887 PPD patients from 12 randomised controlled trials were included in the quantitative meta-analysis, with 443 patients in the treatment group and 444 patients in the control group. Patients in the acupuncture group had significantly better performances assessed by the Hamilton Depression Scale than those in the control group, and the pooled MD was -1.27 (95% CI: -2.55 to 0.01; p = 0.05, I = 83%) in the random-effect model. In addition, significantly better performance in the effective rate was observed in the acupuncture group than in the control group, and the pooled RR was 1.20 (95% CI: 1.09 to 1.33; p < 0.0001, I = 46%). However, in subgroup analysis for the acupuncture therapy alone, only effective rate showed a significantly better performance.; Conclusion: Traditional Chinese acupuncture seems to be effective in improving some symptoms of PPD, although the evidence is uncertain. Therefore, further studies following standardized guidelines with a low risk of bias are needed to confirm the effectiveness of acupuncture in the treatment of PPD.

Toniolo, J., et al. (2021). "Effectiveness of Inhaled Aromatherapy on Chemotherapy-Induced Nausea and Vomiting: A Systematic Review." Journal of alternative and complementary medicine (New York, N.Y.).
	Background: Chemotherapy-induced nausea and vomiting (CINV) are among the most common and feared side effects of cancer treatments. Their presence has a negative impact on the quality of life and morbidity associated with the disease. Despite increasingly effective antiemetic treatments, 40% of cancer patients experience CINV during the acute or delayed phase of their treatment. This distressing experience lived through by a large number of people makes it a priority in the improvement of cancer patients and a daily concern for nurses in cancer care units. In an attempt to alleviate this problem, the idea of using aromatherapy as supportive care has led the authors to research the knowledge available on this subject. Objective: The purpose of this systematic review was to examine the existing scientific evidence regarding the effectiveness of respiratory aromatherapy on CINV in addition to standard treatment compared with their recommended management in people with cancer. Design: Systematic review. Methods: This review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines and queried six databases (PubMed, Scopus, Cochrane Database, Embase, CINAHL, and Google Scholar). An analysis of the risk of bias using the Cochrane "Risks of Bias" tools and a qualitative synthesis of the results of the studies were carried out. Results: Eleven studies were included, nine in adults and two in children. Seven out of nine studies showed statistically significant results in adults with either direct or dry inhalation. Four out of seven alleviated both nausea and vomiting thanks to peppermint, ginger essential oil; three decreased nausea only with chamomilla, ginger or cardamom essential oil. Atmospheric diffusion and the use of inhaled aromatherapy in children did not show any benefit. Conclusions: Results appear promising for the use of direct inhaled aromatherapy in the management of CINV. However, most of the studies found the women concerned suffered from gynecologic cancers and had certain methodological limitations. Indeed, small samples and a wide variety of interventions were studied (different essential oils, number of drops of essential oils used, method of administration, etc.), making it impossible so far to generalize these results. Studies with a more robust methodology and larger samples will make it possible to confirm the potential usefulness of this complementary treatment.

Toohey, K., et al. (2023). "Clinical updates on the effects of high intensity interval training (HIIT) exercise in people diagnosed with cancer. A systematic review and meta-analysis." Journal of Science and Medicine in Sport 26(12): 667-675.
	Objectives: To provide an updated critical evaluation on the effectiveness of high intensity interval training (HIIT) on health outcomes amongst cancer survivors. Design(s): Systematic review and meta-analysis. Method(s): A systematic search was conducted using databases CINAHL and Medline (via EBSCOhost platform), Scopus, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials. Randomised, controlled, exercise trials involving cancer survivors were eligible. Data on the effects of HIIT amongst individuals diagnosed with cancer at any stage were included. Risk of bias was assessed with the Mixed Methods Appraisal Tool (MMAT). Standardised mean differences (SMD) were calculated to compare differences between exercise and usual care. Meta-analyses (including subgroup analyses) were undertaken on the primary outcome of interest, which was aerobic fitness. Secondary outcomes were fatigue, quality of life, physical function, muscle strength, pain, anxiety, depression, upper-body strength, lower-body strength, systolic and diastolic blood pressure. Result(s): Thirty-five trials from forty-seven publications were included, with intervention durations ranging between 4 and 18 weeks. Breast cancer participants were represented in the highest number of trials (n = 13, 37 %). Significant effects in favour of HIIT exercise for improving aerobic fitness, quality of life, pain and diastolic blood pressure were observed (SMD range: 0.25-0.58, all p < 0.01). Conclusion(s): Participation in HIIT exercise was associated with higher retention and improvements in aerobic fitness, quality of life, pain and diastolic blood pressure. The present results provide updated contemporary evidence for clinicians (e.g., exercise physiologists and physiotherapists) to prescribe HIIT exercise for cancer survivors to improve health before, during and following treatment.Copyright © 2023 The Authors

Topçu, H. O., et al. (2020). "Fertility issue in early stage endometrial cancer patients." Translational cancer research 9(12): 7797-7808.
	Endometrial cancer (EC) is the most common cancer of the female reproductive system in developed countries. The incidence of EC has been increasing in young women. Approximately 4% of cases are aged <40 years. These young women may wish to delay therapy until after they have children. Common complaints in patients with EC include irregular vaginal bleeding, pelvic pain, and enlarged uterus. Imaging techniques such as transvaginal ultrasound (TVUS) or magnetic resonance imaging (MRI) can be utilized in detecting EC. Although the recommended treatment of EC is hysterectomy and bilateral salpingo-oophorectomy with or without systemic lymph node dissection, loss of reproductive function is the primary limiting factor of this surgical approach. Some studies have reported favorable results with high-dose oral progestins or levonorgestrel-releasing intrauterine system or hysteroscopic tumor resection followed by treatment with high-dose oral progestins. The most widely utilized medical treatment regimens are medroxyprogesterone acetate (MPA) 250-600 mg/day or megestrol acetate (MA) 160-480 mg/day. However, there is still a lack of evidence to establish the optimal dose and duration of progestin treatment. Patients with complete remission (CR) who wish to conceive must be encouraged, and referral to a fertility clinic should be offered as soon as possible. The key aspect of fertility-sparing management in women with EC appears to be the selection of appropriate candidates. Owing to the rarity of this condition, management may often be suboptimal. The aim of this review is to assess the current approaches to management of young women with EC who wish to preserve their fertility.

Torosis, M., et al. (2023). "PUDENDAL BLOCK AT TIME OF TRANSVAGINAL PROLAPSE REPAIR DOES NOT IMPROVE POSTOP PAIN: a RANDOMIZED CONTROLLED TRIAL." Neurourology and Urodynamics 42: S58‐S60.
	Introduction: There are conflicting reports on the utility of pudendal nerve blocks (PNB) at the time of transvaginal surgery. No published study has evaluated the efficacy of PNB since the widespread adoption of the Enhanced Recovery after Surgery (ERAS) pathway, which focuses on a multimodal approach to facilitate recovery. We sought to determine if PNB at the time of vaginal reconstructive surgery reduces opioid use and improves pain scores in the immediate postoperative period. Methods: In this randomized, double‐blinded, controlled trial at a single academic institution, women ≥18 years old scheduled for transvaginal multicompartment prolapse repair were recruited to participate. Participants were randomized to receive bilateral PNB at the start of the surgical case with 20 ml of 0.5% bupivacaine versus usual care. Both groups had the same perioperative pain control available as per ERAS guidelines. Opioid use in morphine milligram equivalents (MME) for the first 24 hours, pain scores in the first 48 hours, subjective satisfaction with pain control, and return to normal activity were compared between the two groups. The study was powered to detect a primary outcome of a 5.57 MME difference in opioid use in the first 24 hours between groups. Results: Forty‐four patients were randomized from January 2020 to April 2022. PNB and control group were well matched in demographic and surgical data, except for a greater number of anterior repairs in the PNB group (59% vs 86%, p = 0.04). There was no difference in opioid use in first 24 hours (12 MME vs 13 MME), median pain scores at 24 and 48 hours, and overall satisfaction with pain control (Table 1). The PNB did not make an appreciable difference likely due to the overall low levels of pain with adoption of multimodal pain management. Despite relatively low opioid usage and pain scores, median time to return to normal activity was 10 days across both groups. Conclusions: The addition of a PNB at the time of multicompartment prolapse surgery does not improve postoperative pain scores, amount of opioid pain medication used, or satisfaction with surgery. In the era of ERAS pathways, PNB does not add benefit at the time of transvaginal surgery. Further studies are needed to investigate if there is another driver limiting postoperative return to normal function. .

Torres-Gimenez, A., et al. (2024). "Efficacy of contextual therapies in perinatal depression and anxiety: A systematic review and meta-analysis." Journal of Psychiatric Research 169: 209-223.
	Background: There are previous meta-analyses on the efficacy of cognitive behavioral therapy or mindfulness-based therapies in the perinatal period, but no previous review has focused on contextual therapies as a whole. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of contextual therapies on depressive and anxious symptoms in women in the perinatal period. Method(s): A systematic search for randomized clinical trials has been carried out in the PUBMED, CINAHL, Psyc-INFO and Cochrane Library search engines. For the quantitative synthesis, the Morris effect size measure has been used. Result(s): A total of 34 RCTs have been found, of which 30 have been used for meta-analysis. The mean effect size of the studies on depression scores was dppc2 = -0.81 (95% CI = -1.12 to -0.50), while it was dppc2 = -1.04 (95% CI = -1.54 to -0.53) in the case of studies on anxiety scores. These effect sizes decreased to medium effect sizes when corrected for publication bias. Limitation(s): The main limitations are the quality of the included studies, publication bias, and the limited number of studies on contextual therapies other than mindfulness-based therapies. Conclusion(s): In conclusion, this systematic review found a large number of efficacy studies on mindfulness-based therapies and a small number of studies on the other contextual therapies. The effect sizes found are consistent with previous meta-analyses in the perinatal period.Copyright © 2023 Elsevier Ltd

Torshin, I. Y. U., et al. (2020). "The efficacy and safety of a combination of tinidazole and thioconazole in the treatment of vaginal infections." Akusherstvo i Ginekologiya (Russian Federation) 2020(4): 214-222.
	The paper gives the results from a meta-analysis of clinical trials using Gainomax (its standard dose is thioconazole 100 mg, tinidazole 150 mg as a suppository or cream) for the therapy of vulvovaginal candidiasis (VVC), bacterial vaginosis (BV), and trichomaniasis (TM). The meta-analysis included 4 clinical trials (covering 209 patients). The patients' mean age was 35+/-7 years (95% CI, 18-52); all the patients used Gainomax suppositories/cream at the standard dose for 7 days or double dose for 3 days. Gainomax therapy substantially increased the chances of clinical cure of BV (by 20 times; OR 20.4; 95% CI 9.5-43.6), microbiological cure of BV (by 16 times; OR 15.5; 95% CI 7.6-31.5), cures of VVC (by 21 times; OR 21.0; 95% CI 8.8-50.2) and TM (by 29 times; OR 28.8; 95% CI 7.4-111.8). Analyzing individual clinical symptoms revealed associations between drug use and a statistically significant reduction in pathological vaginal discharge (by 25 times; OR 0.04; 95% CI 0.02-0.08), inflammation symptoms (by 33 times; OR 0.03; 95% CI 0.02-0.06), and reddening (by 11 times; OR 0.09; 95% CI 0.06-0.15) during treatment. Only one of the four trials included in the meta-analysis described side effects (in 3 out of 209 patients in the entire sample), no side effects were noted in the remaining trials. Thus, the results of this meta-analysis confirm the high efficacy and safety of the intravaginal use of a combination of tinidazole and thioconazole for the treatment of BV, VVC, and TM.Copyright © 2020, Bionika Media Ltd.. All rights reserved.

Tosatti Jéssica, A. G., et al. (2021). "Influence of n -3 fatty acid supplementation on inflammatory and oxidative stress markers in patients with polycystic ovary syndrome: a systematic review and meta-analysis." The British Journal of Nutrition 125(6): 657-668.
	Polycystic ovary syndrome (PCOS) is defined as a reproductive endocrine disease that results in a low-grade inflammatory and pro-oxidant state. Dietary factors, including n-3 fatty acids, may have a key role in improving metabolic disorders in PCOS patients. The present study aimed to investigate the influence of n-3 fatty acid supplementation on inflammatory and oxidative stress (OS) markers in patients with PCOS. A systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus and Lilacs, until November 2019, was conducted. Randomised clinical trials that reported inflammatory and OS markers as endpoints in women with PCOS receiving n-3 fatty acid supplementation were included. The pooled estimates of the weighted mean differences (WMD) and the standard mean differences (SMD) were calculated. Random effects models were adopted to measure the pooled outcomes. Among the 323 studies retrieved, ten fulfilled the inclusion criteria for a meta-analysis. We founded a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (SMD -0·29 (95 % CI -0·56, -0·02) mg/l) and an increase in adiponectin (WMD 1·42 (95 % CI 1·09, 1·76) ng/ml) concentrations in the intervention group when compared with the placebo group. No statistically significant results were found in the meta-analysis for visfatin, nitric oxide, GSH or malondialdehyde levels or total antioxidant capacity. The data suggest that supplementation of n-3 fatty acids could reduce the inflammatory state in women with PCOS, through a decrease in hs-CRP and an increase in adiponectin levels.

Toulmonde, M., et al. (2022). "Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study." Clinical cancer research : an official journal of the American Association for Cancer Research 28(9): 1765-1772.
	Purpose: Trabectedin has shown preclinical synergy with immune checkpoint inhibitors in preclinical models.; Patients and Methods: TRAMUNE is a phase Ib study investigating the combination of trabectedin with durvalumab through a dose escalation phase and two expansion cohorts, soft tissue sarcoma (STS) and ovarian carcinoma. Trabectedin was given at three dose levels (1 mg/m2, 1.2 mg/m2, and 1.5 mg/m2) on day 1, in combination with durvalumab, 1,120 mg on day 2, every 3 weeks. The primary endpoints were the recommended phase II dose (RP2D) of trabectedin combined with durvalumab and the objective response rate (ORR) as per RECIST 1.1. The secondary endpoints included safety, 6-month progression-free rate (PFR), progression-free survival (PFS), overall survival, and biomarker analyses.; Results: A total of 40 patients were included (dose escalation, n = 9; STS cohort, n = 16; ovarian carcinoma cohort, n = 15, 80% platinum resistant/refractory). The most frequent toxicities were grade 1-2 fatigue, nausea, neutropenia, and alanine/aspartate aminotransferase increase. One patient experienced a dose-limiting toxicity at dose level 2. Trabectedin at 1.2 mg/m2 was selected as the RP2D. In the STS cohort, 43% of patients experienced tumor shrinkage, the ORR was 7% [95% confidence interval (CI), 0.2-33.9], and the 6-month PFR was 28.6% (95% CI, 8.4-58.1). In the ovarian carcinoma cohort, 43% of patients experienced tumor shrinkage, the ORR was 21.4% (95% CI, 4.7-50.8), and the 6-month PFR was 42.9% (95% CI, 17.7-71.1). Baseline levels of programmed death-ligand 1 expression and CD8-positive T-cell infiltrates were associated with PFS in patients with ovarian carcinoma.; Conclusions: Combining trabectedin and durvalumab is manageable. Promising activity is observed in patients with platinum-refractory ovarian carcinoma. See related commentary by Digklia et al., p. 1745. (©2021 American Association for Cancer Research.)

Toyoshima, M., et al. (2021). "A Single Arm Prospective Pilot Study Examining the Efficacy and Safety of Bevacizumab Single Maintenance Therapy Following Platinum-Based Chemotherapy in Patients with Advanced or Recurrent Cervical Cancer." The Tohoku journal of experimental medicine 254(3): 145-153.
	Although the addition of bevacizumab to platinum-based combination chemotherapy has been recommended as a standard regimen for patients with advanced or recurrent cervical cancer, there is no clear evidence regarding the effectiveness of bevacizumab monotherapy as salvage chemotherapy. This study prospectively examined the efficacy and safety of switching from platinum-based chemotherapy combined with bevacizumab to single maintenance therapy in patients with advanced or recurrent cervical cancer. Patients were first treated with standard combination chemotherapy. However, if chemotherapy was discontinued because of an adverse event, bevacizumab monotherapy was continued for patients who agreed to participate in this study and provided written informed consent. The study protocol was approved by the Independent Review Board of Tohoku University School of Medicine (reception number 2017-1-540). A total of 15 patients (median age of 55 years, range 33-69 years) participated in this study. The median number of cycles of bevacizumab single maintenance administration was 8, and the main reasons for discontinuation were disease progression and adverse events. Bevacizumab single maintenance therapy had a disease control rate of 53.3% (CR 40%, PR 6.7%, SD 6.7%). The most frequent grade 3/4 clinical adverse events were proteinuria (5/15) and hypertension (4/15). No treatment-related deaths occurred. Bevacizumab single maintenance therapy was effective as salvage chemotherapy in patients with advanced or recurrent cervical cancer, and the safety profile was generally consistent with those reported in previous studies of bevacizumab monotherapy.

Tracey, A. (2022). "Pelvic Floor Physical Therapy and Its Merit in the Treatment of Female Urogenital Pain." Current pain and headache reports 26(10): 775-782.
	Purpose of Review: Female urogenital pain (FUGP) affects many women and is often a diagnosis of exclusion. The long path to a diagnosis and subsequent treatment frequently leads to suffering on the individual's behalf (Obstet. Gynecol. 121: 645-50, 2013). Additionally, this delay in diagnosis and thus treatment places stress on the US medical system (Obstet. Gynecol. 121: 645-50, 2013). There is a lack of knowledge regarding the scope of pelvic floor physical therapy (PFPT) across the medical community that may prevent physicians from referring patients (J Urol. 193:1545-53, 2015; Sex Med Rev., 2021). PFPT is a low-risk, potentially high-reward option that should be recognized as part of the multidisciplinary approach to managing FUGP.; Recent Findings: Research databases (PubMed and Cochrane) were used to find articles on FUGP between 2005 and 2022. Systematic reviews, randomized controlled trials (RCTs), prospective and retrospective cohorts, and case-study analyses were included in reviewing the literature. The most recent studies in the last 2 years show the benefit of PFPT in certain FUGP diagnoses with improved pain scores and function when compared to no intervention or placebo treatment. The aim of this article is to elucidate the scope of PFPT in the treatment of FUGP with supporting research findings regarding efficacy. It is clear from the literature that PFPT should be recognized by referring physicians as part of a multidisciplinary approach to the treatment of FUGP. (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Trahan, J., et al. (2019). "The Efficacy of Manual Therapy for Treatment of Dyspareunia in Females: A Systematic Review." Journal of Women's Health Physical Therapy 43(1): 28-35.
	Background: Pelvic floor physical therapy is a noninvasive option for relieving pain associated with dyspareunia, genital pain associated with sexual intercourse. Manual therapy is a clinical approach used by physical therapists to mobilize soft tissues, reduce pain, and improve function. To date, the systematic efficacy of manual therapy for treating dyspareunia has not been investigated.; Objective: To examine the efficacy of manual therapy in reducing pelvic pain among females with dyspareunia.; Study Design: Systematic review.; Methods: A systematic literature search was conducted in MEDLINE, EMBASE, and CINAHL databases for articles published between June 1997 and June 2018. Articles were reviewed and selected on the basis of defined inclusion and exclusion criteria. The articles were assessed for quality using the PEDro and Modified Downs and Black scales.; Results: Three observational studies and 1 randomized clinical trial met inclusion criteria. The primary outcome measured was the pain subscale of the Female Sexual Function Index. All studies showed significant improvements in the pain domain of the Female Sexual Function Index ( P < .5), corroborating manual therapy as a viable treatment in relieving pain associated with dyspareunia. However, the quality across studies ranged from poor to good.; Conclusions: Although these findings support the use of manual therapy for alleviating pain with intercourse, few studies exist to authenticate this claim. Moreover, the available studies were characterized by small sample sizes and were variable in methodological quality. More extensive research is needed to establish the efficacy of manual therapy for dyspareunia and the specific mechanisms by which manual therapy is beneficial.; Competing Interests: The authors declare no conflicts of interest.

Training, A. and R. Hospital (2021). Comparison of the Effects of Different Massage Techniques in Women With Primary Dysmenorrhea.
	No Results Available Other: Classic massage group|Other: Connective tissue masage Pain intensity|Pressure pain threshold|Primary dysmenorrhea (PD)-related symptoms|Functional and emotional effects Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 2021/12/01 December 2022

Training Kanuni Sultan, S. and R. Hospital (2023). Comparison of Vaginal Hyaluronic Acid Treatment Over Autologous Platelet Rich Plasma Treatment for Genitourinary Syndrome of Menopause.
	No Results Available Biological: Platelet Rich Plasma treatment|Drug: Vaginal Hyaluronic Acid supplement Vaginal health index score (VHIS)|The Vulvovaginal Symptom Questionnaire (VSQ)|Day-to-Day Impact of Vaginal Aging Questionnaire|vaginal maturation index|vaginal health index Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment KanuniSSEAH3 December 1, 2023

Tramacere, F., et al. (2022). "Assessment of Sexual Dysfunction in Cervical Cancer Patients after Different Treatment Modality: A Systematic Review." Medicina (Kaunas, Lithuania) 58(9).
	Background and Objectives : Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB-IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods : We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results : One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46-56 years). The median follow-up was 12 months (range 0-60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions : Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.

Tran Huy, P., et al. (2022). "Retraction notice to ‘The impact of an endometrial receptivity array on personalizing embryo transfer for patients with infertility: a meta-analysis’ [F&S Reviews 3 (2022) 157-173]." F&S Reviews 3(3): 157-173.
	This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the ASRM Publications Committee and the Editor in Chief of F&S Reviews. The Committee and Editor examined concerns related to the methodology used for the meta-analysis and determined that two flaws undermine the validity of the conclusions presented in the meta-analysis. (1) Three out of the four randomized controlled trials incorporated in the analysis were, in fact, the same single study at different stages, which resulted in the same patients being counted multiple times. This was verified by Dr. Ruiz, an author of these publications (2.) Cohort studies with different designs and comparisons were pooled inappropriately. The Journal regrets that these flaws were not detected during peer review.

Tran, N., et al. (2024). "Surgical outcomes of pelvic organ prolapse."
	
Tranoulis, A., et al. (2020). "Use of electrochemotherapy in women with vulvar cancer to improve quality-of-life in the palliative setting: a meta-analysis." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 30(1): 107-114.
	Introduction: Electrochemotherapy involves the use of transient tumor permeabilization via electric pulses in combination with low-dose chemotherapeutic agents. It has recently emerged as an alternative treatment modality in vulvar cancer. The aim of this meta-analysis was to ascertain the effectiveness of electrochemotherapy in the context of palliative care.; Methods: The following databases were searched: MEDLINE, Scopus, and Cochrane Database, to identify all registered articles pertaining to palliative vulvar cancer treatment with electrochemotherapy from inception until August 2019, in line with PRISMA guidelines. A single-proportion meta-analysis was performed for the outcomes of overall response, complete response, partial response, stable disease, and progressive disease raterespectively, using the random-effect model. Sensitivity analysis was performed to address heterogeneity.; Results: Four studies were included totaling 104 women. The studies were of moderate quality. Pooled results from four studies rendered a summary proportion of 78.8% (95% CI 70.4% to 86.1%) for the outcome of overall response. The median age ranged between 68 and 85 years. The sample size per study ranged between eight and 61 women. The tumors' histological types included: squamous-cell carcinoma (96.2%), Paget's disease (2.9%), and malignant melanoma (0.9%). A total of 65 patients (62.5%) presented with a single nodule, whilst 39 patients (37.5%) presented with multiple nodules. Eighty-nine women (85.6%) were previously submitted to other treatment modalities. The overall response rate ranged from 73.2% to 80.9%. The pooled proportion for the outcomes of complete and partial response rate was 48.7% (95% CI 30.74% to 61.5%) and 30.2% (95% CI 21.7% to 39.4%), respectively. The follow-up ranged from 1 to 51 months. No severe adverse effects were reported. The safety profile of electrochemotherapy was favorable.; Conclusions: Electrochemotherapy is an effective and minimally invasive treatment modality in the palliative care management of patients with vulvar cancer. The effective control of vulvar tumors by electrochemotherapy may contribute to improvement of quality-of-life. In light of the moderate quality of evidence, a multi-center cooperation is warranted to confirm its palliative benefit.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Tranoulis, A., et al. (2019). "Gestational trophoblastic neoplasia: a meta-analysis evaluating reproductive and obstetrical outcomes after administration of chemotherapy." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 29(6): 1021-1031.
	Introduction: Gestational trophoblastic neoplasia represents a rare placental malignancy spectrum that is treated with single- or multi-agent chemotherapy. This disease often impacts women of childbearing age, making post-chemotherapy fertility and obstetrical outcomes an important consideration. We aimed to ascertain the pregnancy rates and obstetric outcomes in women with gestational trophoblastic neoplasia after undergoing treatment with chemotherapy.; Methods: A systematic literature review was conducted to identify studies that reported post-chemotherapy fertility and obstetric outcomes among women with gestational trophoblastic neoplasia. We performed a single-proportion meta-analysis for the outcomes of conception/pregnancy rate, term live birth rate, first and second trimester spontaneous abortions rate, stillbirth rate, premature delivery rate, and fetal/neonatal malformation rate.; Results: A total of 27 studies were included in the analysis. The median age ranged between 25.5 and 33.1 years. The pregnancy rate among women with a desire to conceive, comprising a total of 1329 women and 1192 pregnancies, was 86.7% (95% CI 80.8% to 91.6%). The term live birth rate in 6752 pregnancies was 75.84% (95% CI 73.4% to 78.2%). The adverse pregnancy outcomes were seemingly comparable to those of the general population apart from a minor increase in the stillbirth rate. The pooled proportion for the outcome of malformation rate was 1.76% (95% CI 1.3% to 2.2%). The repeat mole rate in 6384 pregnancies was 1.28% (95% CI 0.95% to 1.66%). Subsequent sub-group analysis indicated that neither multi-agent chemotherapy nor conception within 12 months post-chemotherapy increased the adverse obstetric events risk or fetal malformations.; Conclusions: Nearly 90% of patients desiring future fertility after chemotherapy for gestational trophoblastic disease were able to conceive. In addition, adverse pregnancy outcomes were similar to that in the general population. Multi-agent chemotherapy does not seemingly increase the malformation rate.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Trapani, S., et al. (2024). "Mindfulness-Based Interventions During Pregnancy and Long-Term Effects on Postpartum Depression and Maternal Mental Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Journal of Integrative and Complementary Medicine 30(2): 107-120.
	Objectives: Preventing postpartum depression (PPD) is a public health goal. The scientific literature has demonstrated the short-term efficacy of Mindfulness-Based Interventions (MBIs) delivered during pregnancy on PPD. Nevertheless, the long-term outcomes of MBIs are still unclear. Design(s): Systematic review and meta-analysis of randomized controlled trials (RCTs). Four databases were searched to identify RCTs focused on describing the efficacy of MBIs on PPD and published in English up to February 2022. Settings/Location: The study was conducted globally. Subjects: Pregnant women who received MBIs. Intervention(s): MBIs were delivered during pregnancy in the included RCTs. Outcome Measures: Data collection and analysis effect size were combined using a random-effects model. The reporting in this study was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Result(s): Six studies were included. The overall effect size significantly reduced PPD symptoms severity in the MBI group versus the control group in the first 3 months after childbirth (standardized mean difference = -0.26; 95% confidence interval = -0.51 to -0.01; I2 = 30.65%). The effects of MBIs were significant in women who started MBIs with a low risk of developing PPD. Conclusion(s): MBIs delivered during pregnancy have long-term benefits for PPD. Implications for Practice: Further studies focused on testing MBIs starting during pregnancy and lasting over the postpartum and modulating the intensity of delivering MBIs based on the risk for developing PPD are needed to inform the practice with solid evidence.Copyright © 2024, Mary Ann Liebert, Inc.

Treister-Goltzman, Y. and R. Peleg (2021). "Melatonin and the health of menopausal women: A systematic review." Journal of pineal research 71(2): e12743.
	Melatonin is involved in multiple changes that characterize the aging and can potentially be a safe and effective treatment for menopausal women. The aim of this study was to carry out a systematic review of the medical literature on the health benefits of oral melatonin administration on menopausal women. The electronic databases PubMed, Scopus, and Web of Science were searched systematically on interventional studies that evaluated the association between oral melatonin administration and the health of menopausal women. Risk for bias was assessed for randomized, controlled studies by the RoB v.2 tool and for non-randomized trials by the ROBINS-I tool. Twenty-four studies on melatonin treatment in various aspects of women's health were included in the final systematic review. The studies included 1,173 participants. No evidence was found for an independent effect of melatonin on hemodynamic measures or markers of glucose metabolism. There is some evidence that very low-density lipoprotein and triglycerides levels increase during melatonin administration. There is a fair amount of evidence that melatonin treatment has a favorable effect on bone density and BMI. Melatonin treatment improves EEG patterns and subjective sleep quality in postmenopausal women with preexisting sleep impairment. In a dose of 3 mg and above, melatonin improves climacteric symptoms in one or more domains. The vast majority of the studies had a low risk for bias. In light of multiple health benefits and an excellent safety profile, melatonin administration should be considered in menopausal women. (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Trent, M., et al. (2021). "Using Innovation to Address Adolescent and Young Adult Health Disparities in Pelvic Inflammatory Disease: Design of the Technology Enhanced Community Health Precision Nursing (TECH-PN) Trial." The Journal of infectious diseases 224(Supplement_2): S145-S151.
	New approaches to pelvic inflammatory disease (PID) care among adolescents and young adults (AYAs) that optimize self-care and personalize treatment are warranted to address age and racial-ethnic PID-related health disparities. Here we describe the 13-month preliminary feasibility and acceptability outcomes of recruitment, retention, and intervention delivery for Technology Enhanced Community Health Precision Nursing (TECH-PN) randomized controlled trial. Urban AYAs 13-25 years assigned female sex at birth with acute mild-moderate PID provided baseline and follow-up interview data and vaginal specimens for sexually transmitted infection (STI), cytokine, and microbiota assessment. All participants received medications and text-messaging support. Participants were block randomized to either control or intervention. Control participants received 1 community nursing visit with self-management for interim care per national guidelines. Intervention participants received unlimited precision care services driven by interim STI and macrolide resistance testing results by an advanced practice provider. In the first 13 months, 75.2% patients were eligible, and 76.1% of eligible patients enrolled. Of the participants, 94% completed the intervention and 96%, 91%, and 89%, respectively, completed their 14-, 30-, and 90-day visits. Baseline laboratory results revealed infection rates that were highest for Mycoplasma genitalium (45%) followed by Chlamydia trachomatis (31%). Preliminary enrollment, STI, intervention delivery, and retention data demonstrate the feasibility and acceptability of the TECH-PN intervention and support rationale for precision care for PID among urban AYAs. ClinicalTrials.gov Identifier. NCT03828994.

Tresch, C., et al. (2023). "Enhanced Recovery after Pelvic Organ Prolapse Surgery." Journal of Clinical Medicine 12(18).
	The objective of this study was to review on the influence of enhanced rehabilitation in pelvic organ prolapse surgery outcomes, specifically focusing on length of hospital stay, hospital costs, pain, morbidity, and patient satisfaction. Following the PRISMA model and using PubMed as a source, eight articles pertaining to prolapse surgery and two articles concerning vaginal hysterectomies were selected, all published between 2014 and 2021. These studies revealed no significant difference in terms of operating time, intra- and post-operative complications, intra-operative blood loss and post-operative pain scores before and after the introduction of the ERAS program. Only one study noted a difference in readmission rates. There was, however, a noticeable decrease in intra-operative and post-operative intravenous intakes, opioid administration, length of stay, and overall hospital costs with the adoption of ERAS. Additionally, with ERAS, patients were able to mobilize more rapidly, and overall patient satisfaction significantly improved.

Trifkovič Klavdija, Č., et al. (2022). "Efficacy of Direct or Indirect Use of Probiotics for the Improvement of Maternal Depression during Pregnancy and in the Postnatal Period: A Systematic Review and Meta-Analysis." Healthcare (Basel, Switzerland) 10(6).
	The mother and infant form a unique bond, with maternal mental health affecting the interactions with the infant and infant behaviours impacting maternal mental health. One of the possible mechanisms influencing maternal mental health is the manipulation of the gut-brain axis by consuming probiotic supplements. Probiotics can also have an indirect influence on maternal mental health via the modulation of the infant microbiome and consequently improving the infant's health and thus, indirectly leading to an improvement in maternal mood. This systematic review evaluated the efficacy of probiotics on maternal mental health by searching for randomised controlled trials via international databases: Cochrane Library, PubMed, Scopus, ScienceDirect, and Web of Science until January 2022. A meta-analysis was performed using the Cochrane Collaboration methodology where possible. We found seven clinical trials that included the word probiotics and addressed maternal depression and/or anxiety. Of these, five trials investigated the influence of maternal probiotic supplementation on the gut-brain axis. Two trials investigated the indirect influence of probiotics on maternal depression via supplementation of probiotics by infants and subsequent influence on the crying of colicky infants. Meta-analysis of two studies of pregnant and postnatal women and two studies of infants consuming probiotics on the outcome of the Edinburgh Postnatal Depression Scale for mothers showed no statistical difference. The findings indicate that maternal depression is very complex and is influenced by various bidirectional factors. One of the factors that can improve maternal mental health is probiotics, however, careful consideration must be given to correct strain selection as strain-specific effectiveness was observed. Further well-designed, robust clinical studies are warranted.

Trillsch, F., et al. (2022). "Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study." Gynecologic Oncology 165(1): 40-48.
	Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest.; Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed.; Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR] ≥65 0.43, 95%-confidence interval [CI] 0.24-0.81) as compared with younger patients (N = 155, HR <65 0.31 (95%-CI 0.22-0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05).; Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.; Competing Interests: Declaration of Competing Interest Dr. Trillsch reports grants and personal fees from AstraZeneca, Clovis, Eisai, Medac, MSD, PharmaMar, Roche, and Tesaro/GSK, outside the submitted work. Dr. Mahner reports grants and personal fees from AstraZeneca, Clovis, Medac, Novartis, Olympus Europe, PharmaMar, Pfizer, Roche, Sensor Kinesis, Tesaro/GSK, and Teva, outside the submitted work. Dr. Ataseven, Dr. Asher, Dr. Aryal, Dr. Dubot have nothing to disclose. Dr. Clamp reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from AstraZenca, Clovis Oncology, outside the submitted work. Dr. Penson reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from AbbVie, Array BioPharma Inc., AstraZenca, Cancer Panels, Care4ward, Eisai, Genetech, Merck & Co., Roche Pharma, Sutro Biopharma, GSK Inc., Vascular Biogenics Ltd., WebMD, outside the submitted work. Dr. Oza, Dr. Dr. Amit, and Dr. Huzarski have nothing to disclose. Dr. Casado reports grants and personal fees from AstraZenca, Eisai, Lilly, MSD, PharmaMar, Roche, Tesaro, outside the submitted work. Dr. Scambia has nothing to disclose. Dr. Friedlander reports grants and personal fees from AbbVie, AstraZenca, Beigene, MSD, GSK, Takeda, Novartis, Lilly, outside the submitted work. Dr. Colombo reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from AstraZeneca, BIOCAD, Clovis Oncology, Eisai, GlaxoSmithKline, Immonogen, Mersana, MSD, Novartis, Oncxerna, Pfizer, PharmaMar, Roche, Tesaro, outside the submitted work. Dr. Fujiwara reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from MSD, Daiichi Sankyo, Takeda, Genmab, Nano Carrier, Regenerone, Seagen, Zeria, outside the submitted work. Dr. Sonke reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from Biovica, Merck, Novartis, Roche, Seagen, outside the submitted work. Dr. Denys reports grants and personal fees from Pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro, GSK, Teva, outside the submitted work. Dr. Lowe reports other from AstraZeneca (full time employee), outside the submitte work. Dr. Lee reports grants from AstraZeneca, during the conduct of the study. Dr. Pujade-Lauraine reports grants and personal fees from AstraZeneca, Merck, GSK, Roche, Incyte, ARCAGY Research, outside the submitted work. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Trillsch, F., et al. (2022). "AGO-OVAR 2.34/MIROVA: A RANDOMIZED PHASE II TRIAL OF MIRVETUXIMAB SORAVTANSINE (IMGN853), IN FOLATE RECEPTOR ALPHA (FRa) HIGH RECURRENT OVARIAN CANCER ELIGIBLE FOR PLATINUM-BASED CHEMOTHERAPY." International Journal of Gynecological Cancer 32(Supplement 2): A268.
	Introduction/Background Following implementation of targeted therapies to first-line treatment, repeated use of bevacizumab and/or PARPi is often not approved nor has been conclusively proven efficacious for all patients with recurrent ovarian cancer. Accordingly, new combination partners for platinum-based chemotherapy become crucial to improve outcome. For the antibody-drug conjugate, Mirvetuximab soravtansine (MIRV), containing a folate receptor alpha(FRa)- binding antibody, patients with high FRa expression according to PS2+ Scoring (cut-off: >=75% of tumor cells with FRa membrane staining and >=2+ intensity) had significant progression-free survival (PFS) improvements (hazard ratio: 0.55) compared to mono-chemotherapy (median PFS 5.6 vs 3.2 months, P=0.015) in the phase III FORWARD I trial. Preliminary data for combination of MIRV with carboplatin from the Phase Ib FORWARD II trial, an ORR of 71% in 17 patients with a median PFS of 15 months, and ORR of 80% in the FRa medium/high (>50% PS2+) subset of 10 patients was noted. MIRV is well-tolerated with a manageable safety profile. Methodology Eligible patients for this multicenter, randomized, two-arm, open-label, comparative phase II trial have recurrent, FRa high epithelial cancer of the ovary, fallopian tube or peritoneum and measurable disease. Patients are eligible for platinum-based chemotherapy, had at least one prior chemotherapy, but are not candidates to receive bevacizumab. Patients with wildtype BRCA1/2 mutation status and patients with a deleterious mutation and prior PARPi therapy can be included. Following pre-screening for high FRa expression, 136 patients are randomized (1:1) to a) experimental arm: Carboplatin + MIRV 6 mg/kg IV d1 (6 cycles q21d) followed by MIRV monotherapy until disease progression or b) control arm: Platinum-based chemotherapy (6 cycles) followed by PARPi or standard of care. The primary endpoint PFS will be assessed by modified RECIST 1.1. Key secondary endpoints include overall survival, ORR, and quality of life. NCT04274426 Results Enrolment started. Conclusion Trial in Progress.

Trillsch, F., et al. (2022). "A randomized phase II trial of mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRalpha)-high recurrent ovarian cancer eligible for platinum-based chemotherapy." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: Despite radical primary surgery and carboplatin/paclitaxel-based chemotherapy in combination with anti-angiogenic bevacizumab and/or PARP inhibitors (PARPi), most patients (pts) with advanced ovarian cancer (OC) will relapse. Following the implementation of these targeted therapies to first-line treatment, repeated use of bevacizumab and/or PARPi is often not approved nor has conclusively been proven efficacious for all pts with recurrent OC. New combination partners for platinumbased chemotherapy remain important to improve outcome. The antibody-drug conjugate Mirvetuximab soravtansine (MIRV) is comprised of a folate receptor alpha (FRalpha)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. Results from the phase III trial FORWARD I revealed in an exploratory analysis that pts with high FRalpha expression following PS2+ Scoring (cut off: >=75% of tumor cells with FRalpha membrane staining and >= 2+ intensity) had significant progression- free survival (PFS) improvements with a hazard ratio of 0.55 compared to monochemotherapy (median PFS 5.6 vs 3.2 months, P=0.015) and high activity was most recently confirmed in the SORAYA trial with an overall response rate (ORR) of 32.4%. Preliminary data for the combination of MIRV with carboplatin exist from the Phase 1b FORWARD II trial, which resulted in an ORR of 71%, observed in 17 pts with a median PFS of 15 months, and an ORR of 80% in the FRalpha medium/ high (>50% PS2+) subset of 10 pts. MIRV is well-tolerated with a manageable safety profile. Method(s): Eligible pts for this multicenter, randomized, two-arm, open-label, comparative phase II trial must have recurrent, FRalpha high epithelial cancer of the ovary, fallopian tube or peritoneum and have measurable disease. Pts are eligible for platinum-based chemotherapy with a platinum-free interval of more than 3 months and had at least one prior chemotherapy, but are not candidates to receive bevacizumab for the current relapse. Pts can be included irrespective of wildtype BRCA1/2 mutation status, pts with a deleterious mutation are required to have received prior PARPi therapy. Following prescreening for high FRalpha expression in FFPE tumor tissue according to PS2+ scoring, 136 pts are randomized (1:1) to: a) Control arm: Platinum-based combination chemotherapy (for 6 cycles) followed by PARPi if indicated or standard of care or b) Experimental arm: Carboplatin + MIRV 6 mg/kg adjusted ideal body weight (AIBW) IV d1 (6 cycles q21d) followed by MIRV monotherapy 6 mg/kg AIBW IV q21d until disease progression. The primary endpoint of PFS will be assessed by modified RECIST 1.1. Key secondary endpoints include overall survival, ORR, and quality of life. Enrollment started in September 2021.

Trinh, N. T. H., et al. (2023). "Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway." JAMA Psychiatry 80(5): yoi230003.
	IMPORTANCE Approximately one-half of women treated for affective disorders discontinue antidepressant use during pregnancy, yet this discontinuation could lead to relapse post partum. OBJECTIVE To investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study used nationwide registers in Denmark and Norway. The sample included 41 475 live-born singleton pregnancies in Denmark (1997-2016) and 16 459 in Norway (2009-2018) for women who filled at least 1 antidepressant prescription within 6 months before pregnancy. EXPOSURES Antidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using the k-means longitudinal method. MAIN OUTCOMES AND MEASURES Initiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1 year post partum. Between April 1 and October 30, 2022, hazard ratios (HRs) for each psychiatric outcome were estimated using Cox proportional hazards regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models. RESULTS Among 57 934 pregnancies (mean [SD] maternal age, 30.7 [5.3] years in Denmark and 29.9 [5.5] years in Norway), 4 antidepressant fill trajectories were identified: early discontinuers (31.3% and 30.4% of the included pregnancies in Denmark and Norway, respectively), late discontinuers (previously stable users) (21.5% and 27.8%), late discontinuers (short-term users) (15.9% and 18.4%), and continuers (31.3% and 23.4%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies vs continuers. A moderately increased probability of initiation of psycholeptics was found among late discontinuers (previously stable users) vs continuers (HR, 1.13; 95% CI, 1.03-1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR, 1.28; 95% CI, 1.12-1.46). No association between antidepressant fill trajectories and postpartum self-harm risk was found. CONCLUSIONS AND RELEVANCE Based on pooled data from Denmark and Norway, a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) vs continuers was found. These findings suggest that women with severe mental illness who are currently on stable treatment may benefit from continuing antidepressant treatment and personalized treatment counseling during pregnancy.Copyright © 2023 American Medical Association. All rights reserved.

Trius-Soler, M., et al. (2021). "Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women." Nutrients 13(7).
	The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.

Trneny, M., et al. (2022). "ANALYSIS OF PERIPHERAL NEUROPATHY USING CLINICIAN-AND PATIENT-REPORTED OUTCOMES IN THE POLARIX STUDY." HemaSphere 6(Supplement 3): 2076-2077.
	Background: Peripheral neuropathy (PN) is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Aim(s): To evaluate the impact of Pola-R-CHP vs R-CHOP on PN using clinician-and patient-reported outcomes (ClinRO and PRO) data. Method(s): Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or RCHOP. All patients provided informed consent. Pola-R-CHP is an investigational combination. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patientreported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0-44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38-3.68 [Cheng et al. Health Qual Life Outcomes 2020]). Result(s): At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; >80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ~10% more R-CHOP-than Pola-RCHP-treated patients having clinician-reported PN in Cycle (C) 2-5, and a ~+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3-6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Image: Summary/Conclusion: In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs RCHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to RCHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable.

Trneny, M., et al. (2022). "Analysis of peripheral neuropathy (PN) using clinician- and patient-reported outcomes (ClinRO and PRO) in the POLARIX study." Journal of Clinical Oncology 40(16 Supplement 1).
	Background: PN is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Here, we evaluate the impact of Pola-R-CHP vs R-CHOP on PN using ClinRO and PRO data. Method(s): Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or R-CHOP. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patient-reported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0-44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38-3.68 [Cheng et al. Health Qual Life Outcomes 2020]). Result(s): At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; >80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ~10% more R-CHOP- than Pola-R-CHP-treated patients having clinician-reported PN in Cycle (C) 2-5, and a ~+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3-6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Conclusion(s): In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs R-CHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to R-CHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable.

Trop-Steinberg, S., et al. (2023). "Omega-3 Intake Improves Clinical Pregnancy Rate in Polycystic Ovary Syndrome Patients: A Double-Blind, Randomized Study." The Israel Medical Association journal : IMAJ 25(2): 131-136.
	Background: Omega-3 fatty acids promote fertility in males and females and constitute an important factor in the normal development of the fetus.; Objectives: We investigated the effect of omega-3 supplements during ovulation induction treatment in women with polycystic ovary syndrome (PCOS)-related infertility.; Methods: A randomized, double-blind study was conducted for 60 treatment cycles in 34 women with PCOS-related oligo/anovulation referred to the fertility clinic at the Bikur Cholim/Shaare Zedek Medical Center in Jerusalem, who underwent ovulation induction with clomiphene citrate (50 mg). Seventeen women (mean age 33.9 ± 0.9 years) received omega-3 supplements (3 × 600 mg/day) and 17 received placebo capsules (mean age 32.7 ± 0.9 years) for a maximum of two cycles. We recorded their characteristics and data from their serial hormonal blood tests and ultrasound examinations. We also conducted both univariate and multivariate analyses. The primary endpoint was conception.; Results: There were clinical pregnancies in 8/30 (26.7%) treatment cycles for women receiving omega-3 supplements versus 4/30 (13.3%) cycles with placebo. Among overweight/obese women (body mass index [BMI] 25-35), there were clinical pregnancies in 8/27 cycles (29.6%) versus 1/19 (5.3%) with placebo (P < 0.04). For overweight/obese PCOS women, omega-3, lower BMI rates, and higher values of the endometrium's thickness increased the odds of becoming pregnant. No harmful side effects from the omega-3 treatment were reported.; Conclusions: Omega-3 supplements demonstrated beneficial effects for fertility in women diagnosed with PCOS. Among the overweight/obese participants, the increased clinical pregnancy rate was significant.

Tsai, M.-C., et al. (2021). "Comparison of High-Intensity Focused Ultrasound and Conventional Surgery for Patients with Uterine Myomas: A Systematic Review and Meta-Analysis." Journal of Minimally Invasive Gynecology 28(10): 1712-1724.
	Objective: Uterine myomas are one of the most common gynecologic tumors in premenopausal women. The conventional surgical treatments are myomectomy and hysterectomy, but high-intensity focused ultrasound (HIFU) is a new noninvasive treatment creating no surgical wound. The aim of this study was to evaluate the effectiveness and safety of HIFU treatment compared with conventional surgery for patients with uterine myomas.; Data Sources: PubMed, Embase, and the Cochrane Library were searched for studies published before January 2021.; Methods of Study Selection: Studies comparing the outcome of HIFU and conventional surgery-myomectomy and hysterectomy-for patients with uterine myomas were included. We conducted meta-analyses by using a random effects model. Uterine myoma symptom score and quality-of-life score were analyzed using the mean difference (MD). The recovery time and frequency of major adverse events were also evaluated.; Tabulation, Integration, and Results: Ten studies were included. HIFU relieved uterine myoma symptoms significantly when compared with conventional surgery at 6 (MD -1.61; 95% confidence interval [CI], -2.88 to -0.33) and 12 (MD -2.44; 95% CI, -3.68 to -1.20) months after treatment. Similarly, HIFU group improve the quality-of-life score significantly at 6 (MD 2.14; 95% CI, 0.86-3.42) and 12 (MD 2.34; 95% CI, 0.82-3.86) months after treatment when compared with the surgery group.; Conclusion: HIFU could be an effective and safe treatment option for patients with uterine myomas. However, one of its side effects, skin burns, requires further research and discussion. Additional studies involving more randomized controlled trials are warranted. (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Tsai, S. S., et al. (2020). "The Effects of Aromatherapy on Postpartum Women: A Systematic Review." The journal of nursing research : JNR 28(3): e96.
	BACKGROUND: The postpartum period is the most crucial but also the most fragile stage of most pregnancies. The health benefits of aromatherapy have recently become more widely accepted among medical experts. Although a number of studies have examined these health benefits, no systematic reviews have been conducted to assess the effects of aromatherapy on the psycho-physiological health of postpartum women. PURPOSE: This systematic review was conducted to evaluate the effectiveness of aromatherapy interventions on the psycho-physiological health of postpartum women, to determine the methods that were used to measure intervention effectiveness, and to identify the types of interventions that were used. METHOD(S): We searched for studies that evaluated the effects of aromatherapy on postpartum women published in the Chinese or English languages before March 2018. We used online databases such as the Taiwan Journal Index, Centre for European Policy Studies, Cumulative Index for Nursing and Allied Health Literature, Cochrane Library, PubMed, and Social Sciences Citation Index. The search keywords used were "women," AND "postpartum," OR "postnatal" AND "aromatherapy," OR "aroma," OR "essential oils." Only randomized controlled trials including humans as study participants were included. The methodological quality of the trials was assessed using the modified Jadad scale. The quality of the full-text studies was assessed by three reviewers. RESULT(S): The 15 studies that were included in this systematic review were performed in Iran, England, and the United States and included 2,131 participants in total. The numbers of participants in each study ranged between 35 and 635. The review found that the effective duration of aromatherapy varied according to the essential oils that were selected. The visual analog scale was the most frequently used measure of postpartum pain. Most of the studies found that the aromatherapy intervention improved postpartum physiological and psychological health, with positive effects shown on anxiety, depression, distress, fatigue, mood, nipple fissure pain, physical pain, post-cesarean-delivery pain, post-cesarean-delivery nausea, postepisiotomy pain, postepisiotomy recovery, sleep quality, and stress. Most of the studies reported no serious intervention-related side effects. CONCLUSION(S): This systematic review may serve as a reference for healthcare workers in caring for postpartum women. Aromatherapy may be applied as a noninvasive complementary intervention to promote physio-psychological comfort in postpartum women.

Tsakos, E., et al. (2023). "Multi-Port Robotic-Assisted Laparoscopic Myomectomy: A Systematic Review and Meta-Analysis of Comparative Clinical and Fertility Outcomes." Journal of Clinical Medicine 12(12).
	Background: Uterine fibroids are the most frequently diagnosed gynaecological tumours, and they often require surgical treatment (conventional laparoscopic myomectomy-CLM). The introduction and evolution of robotic-assisted laparoscopic myomectomy (RALM) in the early 2000s has expanded the range of minimally invasive options for the majority of cases. This study aims to compare RALM with CLM and abdominal myomectomy (AM).; Methods and Materials: Fifty-three eligible studies adhered to the pre-established inclusion criteria and were subsequently evaluated for risk of bias and statistical heterogeneity.; Results: The available comparative studies were compared using surgical outcomes, namely blood loss, complication rate, transfusion rate, operation duration, conversion to laparotomy, and length of hospitalisation. RALM was significantly superior to AM in all assessed parameters other than operation duration. RALM and CLM performed similarly in most parameters; however, RALM was associated with reduced intra-operative bleeding in patients with small fibroids and had lower rates of conversion to laparotomy, proving RALM as a safer overall approach.; Conclusion: The robotic approach for surgical treatment of uterine fibroids is a safe, effective, and viable approach, which is constantly being improved and may soon acquire widespread adoption and prove to be superior to CLM in certain patient subgroups.

Tsampras, N., et al. (2022). "Recombinant versus bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection: a systematic review and meta-analysis." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(2): 1-5.
	The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The objective of this study was to appraise critically the published randomised controlled trials (RCTs) comparing recombinant hyaluronidase with bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection (ICSI). We performed a comprehensive literature search of the standard medical databases in order to identify the RCTs comparing oocyte denudation with recombinant hyaluronidase or bovine hyaluronidase before ICSI. Three RCTs involving 2445 oocytes collected from 200 women were analysed. There was substantial heterogeneity among the included RCTs. A meta-analysis from the available moderate to high quality trials found no statistical difference in terms of fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.IMPACT STATEMENTWhat is already known on this subject? The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The long-established source of hyaluronidase has been represented by bovine testes, but concern has been raised regarding the possible negative effects over the fragile oocytes by mechanisms involving low enzyme purity, variable concentrations, trauma, prolonged exposure and integration of external DNA in the oocyte. Recombinant human hyaluronidase has been proposed as an alternative in order to counteract the possible negative effects of using animal derived products.What do the results of this study add? A meta-analysis from the available moderate to high quality trials found no statistical difference in fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.What are the implications of these findings or clinical practice and/or further research? Future trials should be powered adequately in order to be able to identify the possible small differences between the study groups and they should be conducted according to the CONSORT guidelines as the absence of blinding for outcome assessors can induce detection bias.

Tsang, W., et al. (2021). "Clinical Application of Tumor Vascular Disrupting Therapy: A Systematic Review and Meta-Analysis." OncoTargets and therapy 14: 5085-5093.
	Purpose: The occurrence, progression, invasion and metastasis of tumors depend on a tumor vascular network. Vascular disrupting agents (VDAs) are a new class of drugs targeting the tumor vasculature, by blocking the existing tumor blood vessels. However, there is no clear consensus on the clinical efficacy of tumor vascular disrupting therapy. In this study, we performed the first systematic review and meta-analysis of published clinical trials focused on tumor vascular disrupting therapies.; Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that used VDAs to treat tumors. After literature screening and data extraction, according to inclusion and exclusion labels, meta-analysis was performed using RevMan5.3 software.; Results: In this meta-analysis, we included 2659 patients from eight randomized controlled trials involving non-small-cell lung cancer, prostate, epithelial ovarian, fallopian tube, and primary peritoneal carcinoma. Compared with the control arm, the experimental arm exhibited an effective improvement of 0.5-year and 1-year survival, as well as the 6-month progression-free survival rate. There was no significant difference between patients in the experimental compared to the control arm with respect to objective response and disease control rates, and 12-month progression-free survival.; Conclusion: Vascular disrupting therapy can effectively prolong the survival of cancer patients. However, for indicators of short-term efficacy, such as objective response rate and disease control rate, there is still a lack of high-quality, large-scale clinical trial data to confirm the effectiveness of VDAs.; Competing Interests: The authors report no conflicts of interest in this work. (© 2021 Tsang et al.)

Tseng, P.-T., et al. (2023). "Pharmacological interventions and hormonal therapies for depressive symptoms in peri- and post-menopausal women: a network meta-analysis of randomized controlled trials." Psychiatry Research 326: 115316.
	Although significant portion of women experience depressive symptoms during or after menopausal transition, there has been considerable controversy over the benefits of hormone replacement therapy (HRT) and antidepressants due to insufficient evidence supporting the superiority of either treatment. This frequentist model based network meta-analysis (NMA) included randomized controlled trials (RCTs) of menopausal depression symptoms management in menopausal women. Seventy RCTs involving a total of 18,530 women (mean age 62.5) were analyzed. The results demonstrated that fluoxetine plus oral HRT [standardized mean difference (SMD)=-1.59, 95% confidence interval (95%CIs)=-2.69 to -0.50] were associated with the largest improvement in depressive symptoms than placebos in overall menopausal women. Similar findings were also noted in the subgroup of participants with a definite diagnosis of depression, while no pharmacological or hormone replacement therapy was better than placebo in the subgroup of post-menopausal women (amenorrhea > 1 year) or in patients without diagnosis of depression. This NMA presented evidence that fluoxetine plus HRT may be beneficial to menopausal women with a definite diagnosis of depression but not to those without depression or post-menopausal women. Trial registration: PROSPERO (CRD42020167459).; Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest. The authors of this work were supported by the following grants: Brendon Stubbs was supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs was partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs was also supported by the Maudsley Charity, King's College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tsiampa, E., et al. (2021). "Impact on ovarian reserve after minimally invasive single-port laparoscopic ovarian cystectomy in patients with benign ovarian cysts: A systematic review and meta-analysis." International Journal of Clinical Practice 75(12): e14875.
	Background/aim: The purpose of this article is to review the published literature on single-port laparoscopic (SPL) ovarian cystectomy and to assess whether the reduced port number affects the ovarian reserve in comparison with the conventional multiport laparoscopic (MPL) ovarian cystectomy.; Materials and Methods: It has been suggested that the most accurate marker of ovarian reserve is the Serum anti-Müllerian hormone (AMH). A review of the current literature was performed based on the preoperative and postoperative AMH after SPL and MPL ovarian cystectomy in adult patients with benign ovarian cysts.; Results: Ovarian cystectomy causes a non-statistically significant reduction in AMH levels four weeks postoperatively in the SPL group compared to the MPL group [MD = 0.11, 95% CI (-0.01, 0.24), P =0 .07]. Operative time was significantly longer, and blood loss was significantly higher in the SPL group. No difference was reported in terms of major or overall postoperative complications between the two groups.; Conclusion: SPL cystectomy may be offered as a minimally invasive surgical alternative for patients who want to preserve their fertility, at the cost of higher blood loss and longer operative time. (© 2021 John Wiley & Sons Ltd.)

Tsiampa, E., et al. (2024). "Perioperative and reproductive outcomes' comparison of mini-laparotomy and laparoscopic myomectomy in the management of uterine leiomyomas: a systematic review." Archives of Gynecology and Obstetrics 309(3): 821-829.
	Objective: To evaluate and compare mini-laparotomy (MLPT) with laparoscopic (LPS) myomectomy perioperative and reproductive outcomes. Method(s): We systematically searched for related articles in the MEDLINE, Embase, Web of Science and the Cochrane library databases. Nine studies (4 randomized, 3 retrospective, 1 prospective and 1 case-control study) which involved 1723 patients met the inclusion criteria and were considered eligible for inclusion. Result(s): Demographic characteristics were similar between the two groups. LPS was associated with shorter hospital stay (p = 0.04), lower blood loss (p < 0.00001), shorter duration of median ileus (p < 0.00001) and fewer episodes of postoperative fever (p = 0.04). None of the reproductive factors examined (pregnancy rate, preterm delivery, vaginal delivery and delivery with caesarean section) in women diagnosed with unexplained infertility and/or symptomatic leiomyomas reached statistical significance although the results represent a small size effect. Conclusion(s): Our analysis demonstrated that LPS seems to be an alternative, safe and reliable surgical procedure for uterine leiomyoma treatment and in everyday practice seems to offer improved outcomes-regarding at least the perioperative period-over MLPT.Copyright © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023.

Tsokkou, S., et al. (2024). "Genetic and Epigenetic Factors Associated with Postpartum Psychosis: A 5-Year Systematic Review." Journal of Clinical Medicine 13(4).
	Purpose: Postpartum psychosis (PPP) is a serious mental health illness affecting women post-parturition. Around 1 in 1000 women are affected by postpartum psychosis, and the symptoms usually appear within 2 weeks after birth. Postpartum mental disorders are classified into 3 main categories starting from the least to most severe types, including baby blues, postpartum depression, and postpartum psychosis. Materials and Methods: In this systematic review, genetic and epigenetic factors associated with postpartum psychosis are discussed. A PRISMA flow diagram was followed, and the following databases were used as main sources: PubMed, ScienceDirect, and Scopus. Additional information was retrieved from external sources and organizations. The time period for the articles extracted was 5 years. Results: Initially, a total of 2379 articled were found. After the stated criteria were applied, 58 articles were identified along with 20 articles from additional sources, which were then narrowed down to a final total of 29 articles. Conclusions: It can be concluded that there is an association between PPP and genetic and epigenetic risk factors. However, based on the data retrieved and examined, the association was found to be greater for genetic factors. Additionally, the presence of bipolar disorder and disruption of the circadian cycle played a crucial role in the development of PPP.

Tsonis, O., et al. (2020). "Upfront debulking surgery for high-grade serous ovarian carcinoma: current evidence." Annals of Translational Medicine 8(24): 1707.
	High-grade serous ovarian carcinoma (HGSOC) is a leading cause of mortality among women worldwide. Currently, there is no clear consensus over the regime these patients should receive. The main two options are upfront debulking surgery with adjuvant chemotherapy or neoadjuvant chemotherapy followed by interval debulking surgery (IDS). The former approach is proposed to be accompanied by lower chemoresistance rates but could lead to severe surgical comorbidities and lower quality of life (QoL). Optimizing patient's selection for upfront debulking surgery might offer higher progression-free and overall survival rates. Further studies need to be conducted in order to elucidate the predictive factors, which are favorable for patients undergoing upfront debulking surgery in cases of high-grade serous ovarian cancer.Copyright © Annals of Translational Medicine. All rights reserved.

Tsonis, O. and J. Kopeika (2023). "Fertility preservation in patients with gynaecologic malignancy: Response to ovarian stimulation and long-term outcomes." European Journal of Obstetrics, Gynecology, and Reproductive Biology 290: 93-100.
	Objective: To the best of our knowledge, the available evidence on the effect and efficacy of controlled ovarian stimulation (COS) in this group of patients remains poorly reported. Concerns related to the impact of stimulation to cancer progression and recurrence, as well as the risk of disease dissemination during egg collection, might explain the aforementioned trend.; Methods: Overall, our FP Service received 192 gynaecological referrals, between 2005 and 2021, regarding gynaecologic conditions mainly cancer related. A total of 68 (35.4%) patients underwent COS. These patients were diagnosed with the following gynaecologic pathologies: 33 cases (48,5%) of cervical cancer were noted (stage 1b1-2b), 25 ovarian pathology (36.7%), 9 cases (13.2%) of endometrial cancer, and a single case of vaginal cancer (1.5%).; Results: The mean age of patients attending the fertility preservation service was 31.5 (std 5.8). The patients presenting to their initial appointment with a mean BMI 24.5 (IQR 6.9) and a median AFC of 12 (IQR 13). The mean duration of COS was 11 days (IQR 3), and the median dose of gonadotrophins was calculated at 300 IU (IQR 75 IU). In 95.4% of the cases, GnRH agonist was used as a trigger for final maturation. The median number of follicles measuring more than 14 mm at the time of trigger was 11 (IQR 8), whereas the median number of oocytes collected was 11 (IQR 9). The complication rate was reported at less than 2%. So far, one in four women of this FP group (17/68, 25% of the overall group) returned to our service to claim their cryopreserved eggs/embryos and successful livebirths were reported in 58.8% of this sample (10/17 cases). The mean time to return to use their oocytes/embryos was 36 months (min value 16 months - max value 85 months). There was no significant difference in mortality rate between patients who received FP vs those who did not (hazard ratio of mortality was estimated at 0.91 (p-value 0.88)).; Conclusion: Based on our findings, ovarian stimulation for patients presenting with gynaecologic malignancy is a safe and efficient method of fertility preservation. Undoubtedly, the sample size is limited, however our results are reassuring and highlight the efficacy of COS for the purpose of FP based on data coming from the largest Assisted Conception Unit of the South-East of the UK.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tsukamoto, S., et al. (2023). "Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: a systematic review." Musculoskeletal surgery 107(1): 7-18.
	Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.Copyright © 2022. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.

Tsz, C., et al. (2023). "The analgesic application of acupuncture in induced abortion: A systematic review and Meta-analysis."
	
Tsz, C., et al. (2024). "The application of acupuncture in threatened miscarriage: A systematic review and Meta-analysis."
	
Tucker, K., et al. (2019). "Physical Activity: Impact on Survival in Gynecologic Cancer." Obstetrical and Gynecological Survey 74(11): 679-692.
	Importance Physical activity has many important health benefits. There is also growing evidence that physical activity plays a role in the prevention and prognosis of multiple cancers, including gynecologic malignancies. Despite the many benefits of physical activity, the number of individuals meeting physical activity recommendations remains low. Objective To examine the role that physical activity plays in the prevention, treatment, and prognosis of gynecologic malignancies and to review the feasibility of physical activity interventions among gynecologic cancer survivors. Evidence Acquisition A PubMed search was performed using relevant terms to identify journal articles related to the proposed subject. The websites of multiple national and international organizations were also used to obtain up-to-date guidelines and recommendations. Results Physical activity appears to decrease the risk of ovarian, endometrial, and cervical cancer, with the strongest evidence of this association seen in endometrial cancer. Although the literature is scarce, participation in physical activity is feasible during active treatment for gynecologic cancers and may decrease symptom burden and increase chemotherapy completion rates. Gynecologic cancer survivors are motivated to increase physical activity, and lifestyle intervention programs are feasible and well received among this population. Conclusions and Relevance Health care providers caring for women with gynecologic malignancies must counsel patients regarding the importance of physical activity. This should include a discussion of the health benefits and, specifically, the cancer-related benefits. A personalized approach to physical activity intervention is essential. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to summarize the physical activity recommendations for adults; describe health benefits of physical activity and review the hypotheses for its role in cancer; assess the general conclusions for the role of physical activity in the setting of gynecologic cancer; and propose considerations or modifications to physical activity in patients who may have treatment or disease-related adverse effects.Copyright © 2019 Wolters Kluwer Health, Inc.

Tuebingen University, H. (2021). Treatment of Cervical Intraepithelial Neoplasia (CIN) Grade III With Non-invasive Physical Plasma.
	No Results Available Procedure: Non-invasive physical plasma Rate of histological complete remission|Rate of partial histological remission|Rate of decreased HPV viral load|Pain and quality of life Female Not Applicable 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ZGynO_CIN_III September 2023

Tunc, A. and Aygul (2021). "Effectiveness of cognitive behavioral therapies in women with breast cancer: A systematic review." Psikiyatride Guncel Yaklasimlar 13(1): 34-51.
	Cognitive Behavioral Therapy (CBT) has been proven by systematic review and meta-analysis studies that it is an effective psychotherapeutic approach for women with breast cancer (WBC) having biological, psychological, and social distress. However, CBT consists of different waves. In recent years, it is found that third wave approaches such as Acceptance and Commitment Therapy (ACT) and Mindfulness Based Cognitive Therapy (MBCT) are used as psychological interventions in breast cancer. In the present study, the aim is to assess the effects of randomized controlled studies based on second and third wave Cognitive Behavioral Therapies on the bio-psycho-social distress of WBC by a systematic review. Literature review was conducted on 3 electronic databases, Google Academic, PubMed, and Ulakbim, by using English and Turkish keywords. Studies executed with second- or third-wave Cognitive Behavioral Therapies in women with breast cancer and with randomized controlled research designs were included in the review. 21 studies complying with the eligibility criteria were found. Among these studies, 16 were categorized as the studies conducted based on Cognitive Behavioral Therapy, 3 based on ACT, and 2 based on MBCT. It is observed that Cognitive Behavioral Therapies are effective in depression, insomnia, cognitive impairment, menopausal symptoms, fatigue related by cancer, physical adaptation, pain, life quality, psycho-social adaptation, self-esteem, and sexual dysfunction. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Tung, K. T. S., et al. (2023). "Maternal n-3 PUFA Intake During Pregnancy and Perinatal Mental Health Problems: A Systematic Review of Recent Evidence." Current nutrition reports.
	PURPOSE OF REVIEW: Pregnant women are vulnerable to mental health problems. Increasing evidence shows that omega-3 polyunsaturated fatty acid (n-3 PUFA) intake during pregnancy is beneficial to maternal perinatal mental health. A systematic review is needed to examine the associations reported in recent studies. The objective of this review was to provide an updated review on the association of antenatal n-3 PUFA intake via different sources (seafood, fish, overall diet, and supplementation) with perinatal mental health problems including depression, anxiety, and psychological distress. RECENT FINDINGS: Searches were performed in Web of Science, Embase, PubMed, and APA PsycInfo databases on 21 June 2021. A total of 2133 records were screened. Data including the name of the first author, publication year, study design, sample characteristics, dietary assessment time and tools, mental health outcome measures, and other relevant information were extracted. In total, 13 articles were included in this review and assessed qualitatively. The results demonstrated that dietary intake of n-3 PUFA during pregnancy was associated with perinatal mental health, but the effect of n-3 PUFA supplementation was influenced by pre-existing medical conditions, socio-demographic characteristics, and dietary and lifestyle patterns during pregnancy. Our review found that sources of n-3 PUFA may have differential effects on woman's mental health during and after pregnancy. Further research using large-size cohort or well-controlled trial protocol is needed to determine the effect of n-3 PUFA supplementation during pregnancy on perinatal mental health.

Turco, L. C., et al. (2020). "Extreme complications related to bevacizumab use in the treatment of ovarian cancer: a case series from a III level referral centre and review of the literature." Annals of Translational Medicine 8(24): 1687.
	In patients undergoing debulking surgery for ovarian cancer (OC), bevacizumab-combined chemotherapy has been reported to be associated with an increased incidence of adverse events (AEs). Reports in the literature have noted the overall morbidity of bevacizumab to be between 3.7% and 9%. The aim of this study is to report uncommon and unusual manifestations of morbidity in surgical cases performed at our third level referral centers for gynecologic oncology. Additionally, we review the rare and severe bevacizumab-related complications that have been described in the literature. We defined as "extreme", the particularly rare and/or severe complications up to determining a life-threatening condition or death, which are related to the use of bevacizumab. A case-series of extreme complications registered at our institutions were reported. In addition, a literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed for this review. The studies collected included: 8 randomized controlled trials (RCT) and 5 prospective observational, 1 prospective phase-IV, 10 prospective phase-II, 2 prospective phase-I, and 20 retrospective studies, as well as 9 case reports. Bevacizumab was administered as primary treatment in adjuvant and neo-adjuvant setting in 16 and 5 studies respectively, as treatment for recurrence in 36 trials, and for secondary cytoreductive surgery (SCS) in 3 studies. The overall population administered with bevacizumab numbered 7,096 women. Extreme complications were observed in 591 patients, with a morbidity rate of the 8.3%. Overall, central nervous system (CNS), cardiovascular, gastrointestinal (GI) and primary infectious complications were seen in 22 patients (0.3%), 261 patients (3.7%), 159 patients (2.2%), and 8 patients (0.13%), respectively. Hemorrhagic and wound complications occurred in 18 women (0.25%), and 112 women (1.6%), respectively. Extreme complications related to the use of bevacizumab are rare, and often go unrecognized. The recognition and immediate management of such rare and life-threatening complications in patients treated at third level referral centers could significantly improve patient survival.Copyright © 2020 AME Publishing Company. All rights reserved.

Turkmen, H. and S. Yoruk (2023). "Effects of heat treatment on dysmenorrhea and its mental health outcomes: A randomized clinical trial." Psychiatric Annals 53(6): 270-281.
	This randomized controlled prospective experimental trial was conducted with 46 students with dysmenorrhea who were randomized in a 1:1 ratio to the heat treatment group (HTG) (n = 23) and control group (CG) (n = 23). To HTG, dry heat was applied for 20 minutes to the lower abdominal region of the subjects when their dysmenorrhea was most severe. Visual Analogue Scale (VAS), the Short Form McGill Pain Questionnaire (SF-MPQ), the Menstrual Attitude Questionnaire (MAQ), and the Depression Anxiety and Stress Scale (DASS) were used in this study. At the first menstrual cycle, both groups received the questionnaires, and no treatment was applied. At the second, third, and fourth menstrual cycles, VAS and SF-MPQ were applied before the treatment (T1), right after the treatment (T2), and 2 hours after the treatment (T3). MAQ and DASS were applied right after the treatment. Seven subjects from HTG and four subjects from CG were excluded from the study on account of their analgesic medicine usage, inability to menstruate, or by their own requests. When HTG and CG were compared, the decrease in the dysmenorrhea pain after the heat treatment in each of the three menstrual cycles was found to be statistically significant (P < 0.05). In each of the four menstrual cycles, depression, anxiety, and stress were detected in each subject in both groups. However, the effectiveness of the treatment was not determined (P > 0.05). In HTG, awareness of the changes during menstruation was diminished with time. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Turkmen, O., et al. (2022). "The effect of adjuvant radiotherapy on oncological outcomes in patients with early-stage cervical carcinoma with only intermediate-risk factors: a propensity score matching analysis." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(7): 3204-3211.
	We aimed to evaluate whether adjuvant radiotherapy had a survival benefit for patients with early-stage cervical carcinoma with intermediate-risk factors. This study included patients who underwent radical hysterectomy and lymphadenectomy according to Wertheim-Okabayashi for stage IB1-IIA2 cervical carcinoma. Each patient had at least one intermediate-risk factor including tumour diameter ≥4 cm, deep stromal invasion, and positive lymphovascular space invasion (LVSI). Patients with lymph node metastasis, parametrial invasion, and positive surgical margins according to the final paraffin section were excluded. In total, 183 patients were included. Seventy-three (39.9%) patients had one, 85 (46.4%) had two, and 25 (13.7%) had three intermediate risk factors. Sixty-seven (36.6%) patients received adjuvant radiotherapy. There was a statistically significant difference in terms of stage, LVSI, and endometrial/uterine invasion between the groups that did and did not receive adjuvant radiotherapy ( p = .024, p = .018, and p = .001, respectively). These two groups were homogenised by performing propensity score matching (PSM) analysis. In the new matched cohort ( n = 134), 5-year disease-free survival (DFS) was 89.5% in the group that received adjuvant radiotherapy and 82% in the group that did not (HR: 0.484, 95% CI: [0.171-1.369]; p = .171). Also, receiving adjuvant radiotherapy was not associated with an improvement in oncologic outcomes in patients with one, two, or more intermediate risk factors. In univariate analysis, none of the risk factors was associated with DFS. In conclusion, adjuvant radiotherapy had no favourable effect on survival outcomes in patients with early-stage cervical carcinoma with only intermediate risk factors.IMPACT STATEMENT What is already known on this subject? Radiotherapy after radical hysterectomy in cervical carcinoma is accepted as the standard of care when high-risk factors - positive surgical margins, lymph node metastasis, and parametrial involvement - are found in the surgical specimen. However, the necessity of adjuvant radiotherapy in patients with intermediate-risk factors - deep stromal invasion, positive LVSI, tumour diameter ≥4 cm - is controversial. What do the results of this study add? We compared patients who received adjuvant radiotherapy and those who did not. No significant difference was found between the two groups in terms of oncologic outcomes. There was no difference between the two groups in terms of pelvic and extrapelvic recurrence rates. The number of positive intermediate-risk factors did not affect survival. Moreover, age, tumour type, stage, number of removed lymph nodes, grade, bilateral salpingo-oophorectomy, and endometrial/uterine invasion were not associated with DFS among patients with stage IB-IIA cervical carcinoma with only intermediate-risk factors. What are the implications of these findings for clinical practice and/or further research? Debate remains over the prognostic factors and the adjuvant treatment options in patients with early-stage cervical carcinoma who possess intermediate-risk factors. Adjuvant radiotherapy can be ignored if initial adequate surgery has been performed in this patient group.

Turkmen, S., et al. (2021). "Neurosteroid involvement in threatened preterm labour." Endocrinology, diabetes & metabolism 4(2): e00216.
	INTRODUCTION: The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABAA receptor. Whether neurosteroid levels and the function of the GABAA receptor are involved in the risk of preterm labour in pregnant women is unknown. METHODS: Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABAA receptor function in both groups was measured with a saccadic eye velocity test (SEVT). RESULTS: Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p = .021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: -3.2, 95% confidence interval (CI): -5.5 to -0.9, p = .012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00-1.04, p = .038). SEVT showed that the women in both groups had similar GABAA receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r = .34, p = .044) and negatively with allopregnanolone (r = -.41, p = .013). CONCLUSIONS: Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABAA receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABAA receptor agonist.

Turktekin, N., et al. (2022). "Endometrial injury and fertility outcome on the day of oocyte retrieval." Annals of Clinical and Analytical Medicine 13(1): 89-92.
	Aim: In this study, we aimed to investigate the effect of mechanical endometrial injury, performed on the day of egg retrieval, on pregnancy rates in patients who underwent IVF/ICSI due to PCOS and planned total embryo freezing. Material(s) and Method(s): Sixty women with PCOS scheduled for total embryo freezing due to the risk of ovarian hyperstimulation syndrome were included in the study. The participants were randomly divided into two groups as treatment and control, with 30 patients in each group. For patients in both groups, standard antagonist protocol for controlled ovarian stimulation was applied. The patients in the treatment group underwent endometrial scratching with a Pipelle cannula after egg collection. The patients in the control group (sham) were reached up to the fundus with a Pipelle catheter, but scratching was not performed. The primary outcome measures of the study were beta-hCG, clinical pregnancy rates (CPR), live birth rates (LBR), and miscarriage rates. Result(s): There was no significant difference between the two groups in terms of the percentage of beta-hCG positive patients, clinical pregnancy and live births (p>0.05). Clinical pregnancy and live birth rates of both groups were recorded as similar. No significant difference was found between the injury group and the control group in terms of miscarriages rates. All of the pregnancies in the scratching group and control group were intrauterine localized and no ectopic pregnancy was encountered. Discussion(s): Injury to the endometrium on the day of egg collection does not cause a significant increase in clinical pregnancy and live birth rates.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Turncliff, R., et al. (2023). "A Phase 3 study evaluating ovarian suppression following three-month leuprolide acetate in combination with endocrine therapy in premenopausal subjects with HR+, HER2-negative breast cancer (OVELIA)." Cancer Research 83(5 Supplement).
	Background: In US clinical practice, GnRH agonists are widely used to suppress ovarian function in pre/perimenopausal patients with breast cancer that is moderate-to high-risk for recurrence. Despite extensive use of leuprolide acetate (LA) for ovarian suppression, regulatory approval for this indication has not been established in the US. Additionally, existing three month formulations may not reliably provide ovarian suppression, as demonstrated by escapes in estradiol (E2). An extended-release LA product with a 3-month dosing period specifically developed for ovarian suppression in patients with breast cancer could fill this unmet need. TOL2506 is a 3-month, extended-release formulation of 30 mg of LA. This combination of active drug and in situ polymeric extended release technology is expected to deliver higher exposure to drug than the currently available 3-month (22.5 mg) formulations of LA marketed for advanced prostate cancer and potentially reduce escapes in E2 over the dosing period. Method(s): TOL2506A (OVELIA) is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. Approximately 250 subjects will be enrolled targeting 220 evaluable subjects, with 30% aged 40 years or younger. Subjects must be premenopausal women, age 18-49 (inclusive), with a diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative per ASCO CAP guidelines), who are candidates for ovarian suppression with endocrine therapy. For subjects receiving chemotherapy, premenopausal status will be determined prior to initiating chemotherapy. Male subjects with HR+, HER2-negative breast cancer may also be eligible, but will be evaluated for safety analyses only. Eligible subjects will enter the 48 week Treatment Period in 2 groups: those receiving tamoxifen concurrently with TOL2506 or those who initiate therapy with an aromatase inhibitor (AI; letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, if E2 < 20 pg/mL has been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the Investigator's discretion. Subjects will receive 4 doses of TOL2506 every 12 weeks over the 48 week study duration. The primary endpoint to be evaluated is ovarian suppression, defined as >= 90% of subjects with LH levels < 4 IU/L at Week 6. Secondary endpoints include suppression of LH, E2 (< 20 pg/mL for tamoxifen cohort and < 2.72 pg/mL for AI cohort) and absence of menses at weeks 6, 12, 24, 36, and 48. NCT04906395.

Turner, J., et al. (2023). "Telehealth interventions for physical activity and exercise participation in postpartum women: A quantitative systematic review." Preventive Medicine 167: 107413.
	Postpartum women are one of the least physically active vulnerable populations globally and telehealth has been proposed as a potential method of delivering effective exercise interventions for this population. However, clinical practice guidelines are based upon the recommendations for the general population and therefore, the most efficacious exercise dose and the delivery method for this population is unclear. This quantitative systematic review will examine the implementation and outcomes of telehealth exercise interventions in the postpartum population to synthesise the degree to which these outcomes have been assessed and evaluated. Five databases were searched from January 2001 to March 2022. Studies implementing synchronous telehealth exercise interventions for postpartum women were included. Interventions were examined against the Template for Intervention Description and Replication (TIDieR) checklist that assesses intervention reporting completeness and replicability. Of the 1036 records identified, 16 studies progressed to data extraction. Six interventions provided individualised exercise prescription, and only four were delivered by university-level exercise practitioners. Physical activity participation was well reported, however health-related outcomes (i.e., muscular strength and aerobic capacity) were very minimally assessed. Only one intervention utilised modern video conferencing as the primary telehealth communication method. With the minimal assessment of health-related outcomes, there is limited scope to assess the effectiveness of these interventions for postpartum women. Future research interventions need to be reported according to a validated trial reporting system and focus on relevant health related outcomes including postpartum depressive symptoms, quality of life, cardiovascular fitness, muscular strength and body composition.Copyright © 2023 Elsevier Inc.

Turner, S., et al. (2023). "Directive clinique no 443b: Opioides aux differentes etapes de la vie des femmes: Grossesse et allaitement." Journal of Obstetrics and Gynaecology Canada 45(11): 102146.
	Objectif: Presenter aux professionnels de la sante les donnees probantes concernant l'utilisation des opioides et la sante des femmes. Les domaines d'interet sont la grossesse et les soins post-partum. Population cible: Toutes les femmes qui utilisent des opioides. Resultats: Un dialogue ouvert et eclaire sur l'utilisation des opioides ameliorera les soins aux patientes. Benefices, risques et couts: L'exploration de l'utilisation d'opioides par une approche tenant compte des traumatismes anterieurs donne au professionnel de la sante et a la patiente l'occasion de batir une alliance solide, collaborative et therapeutique. Cette alliance permet aux femmes de faire des choix eclaires. Elle favorise le diagnostic et le traitement possible du trouble lie a l'utilisation d'opioides. L'utilisation ne doit pas etre stigmatisee, puisque la stigmatisation affaiblit le partenariat (le partenariat entre patiente et professionnel de la sante). Les professionnels de la sante ceus-ci doivent comprendre l'effet potentiel des opioides sur la sante les femmes enceintes et les aider a prendre des decisions eclairees sur leur sante. Donnees probantes: Une recherche a ete concue puis effectuee dans les bases de donnees PubMed et Cochrane Library pour la periode d'aout 2018 a mars 2023 des termes MeSH et mots cles suivants (et variantes): opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome et breastfeeding. Methodes de validation: Les auteurs ont evalue la qualite des donnees probantes et la force des recommandations en utilisant le cadre methodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les definitions et tableau A2 pour l'interpretation des recommandations fortes et conditionnelles [faibles]). Professionnels concernes: Tous les professionnels de la sante qui prodiguent des soins aux femmes et aux nouveaux-nes. Resume pour Twitter: La consommation d'opioides pendant la grossesse coincide souvent avec des problemes de sante mentale et est associee a des consequences nefastes pour la mere, le foetus et le nouveau-ne; le traitement des troubles lies a la consommation d'opioides par agonistes peut etre sur pendant la grossesse lorsque les risques sont plus nombreux que les avantages. DECLARATIONS SOMMAIRES: 1. Les opioides creent une forte dependance et sont souvent prescrits pour soulager la douleur. Leur prescription excessive a contribue a l'epidemie d'opioides au Canada (elevee). 2. Les opioides ne doivent etre prescrits qu'en cas d'absolue necessite, a la dose efficace la plus faible et pour la duree la plus courte possible (elevee). 3. Les femmes enceintes qui utilisent des opioides illicites sont plus a risque de contracter une infection transmissible sexuellement, d'etre victimes de violence, de poser des gestes violents ou de s'adonner a des activites illegales, de presenter un trouble de sante mental concomitant, de consommer plusieurs substances, d'avoir une mauvaise alimentation et de dependre de l'aide sociale (moyenne). 4. Les changements physiologiques de la grossesse peuvent alterer les proprietes pharmacocinetiques des opioides exogenes (moyenne). 5. L'exposition prenatale aux opioides a ete associee a la naissance avant terme, au nourrisson petit pour l'age gestationnel et a une diminution de la frequence cardiaque foetale, mais il faut recueillir davantage de donnees (faible/moyenne); l'exposition prenatale aux opioides peut entrainer un syndrome de sevrage neonatal des opioides (elevee). 6. Les femmes qui suivent un traitement par agonistes opioides peuvent avoir besoin de plus fortes doses d'opioides a courte duree d'action pour l'analgesie et, dans certains cas, d'opioides a haute affinite pour les recepteurs opioides pour le traitement de la douleur per partum et post-partum (elevee). 7. Les opioides peuvent etre utilises en toute securite pour soulager la douleur pendant le travail chez les femmes qui suivent un traitement par agonistes opioides, mais il pourrait etre cessaire de leur administrer une dose plus forte que chez les femmes naives aux opioides (moyenne). 8. L'utilisation d'antagonistes opioides (naltrexone et naloxone) chez les femmes enceintes presentant un trouble lie a l'utilisation d'opioides reste peu etudiee; par consequent on accuse un manque de donnees sur l'innocuite et l'efficacite des antagonistes opioides chez les femmes enceintes (tres faible). 9. Aider les femmes enceintes a passer d'un traitement par agonistes opioides injectables ou d'une consommation d'opioides illicites a un traitement par agonistes opioides oraux pendant la periode ante partum, la methadone ou la morphine orale a liberation lente peuvent etre preferables a la buprenorphine-naloxone, car ces options ne necessitent pas une periode de sevrage d'opioides avant le debut du traitement (moyenne). RECOMMANDATIONS: 1. Les professionnels de la sante ne devraient prescrire des opioides que lorsque d'autres therapies medicales et psychosociales fondees sur des donnees probantes ont echoue (forte, elevee). 2. A l'interpretation des resultats de l'examen de reactivite foetale ante partum ou per partum et de la surveillance de la frequence cardiaque foetale, le professionnels de la sante doit prendre en compte le ralentissement de la frequence cardiaque foetale cause par les opioides ainsi que la diminution de la variabilite et des accelerations au pic d'action biologique de l'opioide (forte, moyenne). 3. Les professionnels de la sante devraient recommander de ne pas utiliser d'opioides non prescrits, d'opioides illicites ou d'autres substances non prescrites pendant l'allaitement (forte, moyenne), mais les femmes recevant des doses stables d'agonistes opioides ou d'opioides pour la douleur chronique devraient etre encouragees a allaiter (forte, moyenne). 4. Les professionnels de la sante doivent discuter avec leurs patientes enceintes des risques et des avantages des opioides prescrits pour traiter les douleurs chroniques, afin de mettre en balance la probabilite d'une augmentation de la douleur en cas de reduction ou d'arret de la medication et les effets indesirables potentiels sur la grossesse de la poursuite des doses therapeutiques d'analgesiques (forte, elevee). 5. Les professionnels de la sante doivent titrer le traitement opioide pour la gestion de la douleur chronique non cancereuse chez les femmes enceintes a la dose efficace la plus faible, en sachant que la dose peut devoir etre augmentee en raison des changements metaboliques causes par la grossesse (forte, elevee). 6. L'accouchement doit avoir lieu dans un centre qui peut assurer le suivi du sevrage neonatal et les nourrissons exposes aux opiaces pendant la grossesse doivent etre observes attentivement pendant la periode neonatale (forte, elevee). 7. Les professionnels de la sante doivent proposer une therapie de remplacement de la nicotine aux patientes enceintes qui consomment simultanement de la nicotine et des opioides, tout en discutant des risques et des avantages, dans des contextes ou l'acces au tabac ou aux cigarettes est limite (c'est-a-dire a l'hopital pendant les periodes intrapartum et postpartum), comme moyen de reduire la sensibilite a la douleur (forte, faible). 8. Les professionnels de la sante devraient recommander une analgesie peridurale au debut du travail pour les femmes souffrant d'un trouble lie a l'utilisation d'opioides, car cela peut attenuer l'hyperalgesie causee par l'utilisation chronique d'opioides (forte, moyenne). 9. Les professionnels de la sante devraient proceder a un depistage universel de la consommation de substances et des troubles lies a l'utilisation d'opioides chez les patientes enceintes, avec leur consentement, en utilisant des outils de depistage fondes sur des donnees probantes (forte, moyenne). 10. Les patientes enceintes souffrant de troubles lies a la consommation d'opioides devraient etre orientees vers des programmes de soins integres, lorsque ceux-ci sont disponibles et accessibles (forte, moyenne). 11. Les professionnels de l'obstetricaux ne devraient pas tenter de diminuer la dose d pioides ou de proceder a une desintoxication (diminution complete) chez les femmes souffrant d'un trouble lie a l'utilisation d'opioides pendant la grossesse (forte, elevee). Cependant, apres une discussion sur les risques obstetriques et foetaux de la reduction progressive ou de la desintoxication, la patiente peut decider en connaissance de cause de se soumettre a ce processus. Dans ce cas, la dose d'opioides doit etre reduite lentement jusqu'a la dose efficace la plus faible (forte, faible). 12. Les professionnels de la sante doivent recommander un traitement par agoniste opioide aux femmes enceintes souffrant d'un trouble de la consommation d'opioides, en commencant le traitement par la dose efficace la plus faible et en augmentant la dose au fur et a mesure de l'evolution de la grossesse, en raison des changements physiologiques et metaboliques associes a la grossesse (forte, elevee). 13. Les professionnels de l'obstetrique doivent envisager d'augmenter les doses et de fractionner les doses de methadone ou de buprenorphine pour le traitement des troubles lies a l'utilisation d'opioides afin de prevenir le sevrage et la rechute pendant la grossesse, en raison de l'augmentation du metabolisme des opioides au fur et a mesure que la grossesse progresse (forte, elevee). 14. Les femmes recevant des doses stables d'agonistes opioides peuvent avoir besoin d'une augmentation de leur dose au fur et a mesure de la grossesse en raison des changements physiologiques et metaboliques survenant pendant la grosse (forte, elevee). 15. Les professionnels de la sante peuvent recommander et prescrire en toute securite la buprenorphine-naloxone pendant la grossesse d'apres les donnees actuelles. Par consequent, il n'est pas necessaire de faire passer les patientes a un produit a base de buprenorphine seule (forte, elevee). 16. Les professionnels de la sante doit depister l'hepatite C, l'hepatite B et le VIH chez les femmes enceintes presentant un trouble lie a l'utilisation d'opioides (forte, moyenne). Il doit aussi envisager les prelevements vaginaux (ou l'autoprelevement par la patiente) pour depister la chlamydia et la gonorrhee (forte, moyenne). 17. Les professionnels de la sante doit offrir le vaccin contre l'hepatite B selon un calendrier accelere aux femmes enceintes non immunisees qui presentent des facteurs de risque continus pour l'hepatite B (forte, elevee). 18. Bien qu'on accuse un manque de recherches sur le recours a la naloxone pendant la grossesse, la naloxone doit etre administree par tout temoin forme ou tout professionnel de la sante a des fins de reanimation si une surdose d'opioides est soupconnee chez une patiente enceinte, car la prevention du deces maternel par surdose est la priorite absolue (forte, faible).Copyright © 2023

Tuyaerts, S., et al. (2019). "PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer." BMC Cancer 19(1): 506.
	Background: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression.; Methods: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome.; Discussion: In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination.; Trial Registration: EU Clinical Trials Register: EudraCT 2016-001569-97 , registered on 19-6-2017. Clinicaltrials.gov: NCT03192059 , registered on 19-6-2017.

Tuzil, J., et al. (2021). "Health-related quality of life in women with autoimmune thyroid disease during pregnancy and postpartum: systematic review including 321,850 pregnancies." Expert Review of Pharmacoeconomics and Outcomes Research 21(6): 1179-1193.
	Background: Utilities of the general population or expert estimates have been used for all published cost-effectiveness analyses of screening for thyroid disorders in pregnancy. Method(s): A systematic review CRD42019120897 of studies with patient-reported outcomes (PRO) and laboratory evidence of thyroid function/autoimmunity was conducted using PubMed, Cochrane Central, EconLit, SocIndex, DARE, NHS EEDS, Annual Reviews, and CINAHL. Quality was assessed using Joanna Briggs Institute appraisal tool. Result(s): Of 664 abstracts screened, we analyzed 97 full texts. All studies describing the impact of thyroid disease on the generic QoL excluded pregnant and postpartum women. 21 reports of acceptable quality (321,850 pregnancies) determined depression and anxiety with validated tools and/or reported subjective symptoms. During pregnancy, contradictory conclusions were published on the impact of thyroid disease on PRO. Postpartum, antithyroid antibodies coincide with alexithymia and depression, postpartum thyroiditis negatively impacts mood. No conclusion could be drawn on the impact of thyroid hormonal levels. Conclusion(s): The generic QoL in autoimmune thyroid disease during pregnancy has never been described, which represents an obstacle for the construction of economic models. We found contradictory information on the impact of thyroid disease on depression, anxiety, and specific symptoms.Copyright © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Tymon-Rosario, J., et al. (2021). "Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu." Gynecologic Oncology 163(1): 93-99.
	OBJECTIVE: Due to previously reported trastuzumab safety concerns and the scant data available in endometrial cancer patients, we sought to assess the safety, tolerability and toxicity profile of trastuzumab in patients with advanced/recurrent uterine serous carcinoma (USC) that overexpress HER2/neu in our multicenter randomized phase II trial. METHODS: Patients were randomized 1:1 to receive carboplatin/paclitaxel (C/P) for 6 cycles ± trastuzumab (T) with the experimental arm continuing to receive single agent trastuzumab maintenance treatment until disease progression/toxicity. Progression-free-survival was the primary endpoint; overall-survival and toxicity were secondary endpoints. Adverse events (AEs) were compared between treatment arms. RESULTS: There were 28 patients in the C/P arm and 32 patients in the experimental (C/P + T) arm. Fifty-eight patients (97%) experienced 977 treatment-related AEs of which 875 (89.6%) were low-grade (grade 1-2) and 102 (10.4%) were high-grade (grade 3-5). The mean ± standard deviation of AEs per patient was 15.5 ± 16.3 in the C/P arm and 17.0 ± 16.0 in the C/P + T arm. Gastrointestinal AEs were the most common in both arms (n = 155, 15.7%) of which 94.2% were low-grade (n = 146). Importantly, no significant difference between treatment arms was detected in any system-organ class of AE including cardiac AE. Five (17%) of 29 patients who received prolonged trastuzumab maintenance therapy had no sign of cumulative toxicity after an average (range) of 5.1 (4.2-6.3) years. CONCLUSIONS: Trastuzumab appears to be safe and has a manageable toxicity profile both when used in combination with chemotherapy and when used for single agent maintenance in patients with HER2/neu positive USC. This safety profile is reassuring given the proven efficacy of trastuzumab in advanced/recurrent HER2/neu positive USC.

Tzanis, A. A., et al. (2024). "Uterine artery embolisation versus myomectomy for the management of women with uterine leiomyomas: a systematic review and meta-analysis." American Journal of Obstetrics and Gynecology.
	OBJECTIVE: To investigate whether uterine artery embolisation (UAE) offers better quality of life (QoL) compared to myomectomy in premenopausal women diagnosed with leiomyomas of the uterus. DATA SOURCES: We searched the electronic databases PubMed and Cochrane Central Register of Controlled trials to January 2023. STUDY ELIGIBILITY CRITERIA: We considered randomised controlled trials (RCTs) comparing UAE with myomectomy in women of premenopausal age suffering from uterine leiomyomas. STUDY APPRAISAL AND SYNTHESIS METHODS: Primary outcome was QoL. Secondary outcomes were re-intervention rate and timing, successful pregnancy, stillbirth and miscarriage, caesarean section upon delivery, and peri-operative morbidity. We performed time-to-event and standard pairwise meta-analyses, as appropriate. Certainty of the evidence was assessed in line with GRADE methodology. RESULT(S): Six RCTs met our inclusion criteria. Meta-analysis suggested little to no difference in terms of QoL between UAE and myomectomy (SMD = 0.05, 95% CI [-0.38 - 0.48], I2 = 92%, very low certainty of evidence). Sensitivity analysis including RCTs which included solely myomectomy procedures in the control arm, demonstrated better QoL for women treated with myomectomy (SMD = -0.32, 95% CI [-0.49 - -0.15], I2 = 15%). With regard to re-intervention, myomectomy was likely associated with a decreased risk for future re-intervention (RR = 0.32, 95% CI [0.15 - 0.69], I2 = 60%, low certainty of evidence) as well as a more prolonged time interval since a potential re-intervention due to recurrence compared to UAE (HR = 0.41, 95% CI [0.22 - 0.77], I2 = 77%, low certainty of evidence). No difference was found between the two interventions with respect to severe peri-operative adverse events (RR = 4.13, 95% CI [0.44 - 39.20], I2 = 0%, low certainty of evidence). CONCLUSION(S): UAE is likely associated with increased re-intervention rates and less time to re-intervention compared to myomectomy in premenopausal women diagnosed with uterine leiomyomas. Evidence suggests no difference between the two interventions regarding peri-operative morbidity. UAE may exert no effect on QoL and successful pregnancy, however the evidence is very uncertain.Copyright © 2024 Elsevier Inc. All rights reserved.

Tzanis Alexander, A., et al. (2023). "The role of systematic pelvic and para-aortic lymphadenectomy in the management of patients with advanced epithelial ovarian, tubal, and peritoneal cancer: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 285: 198-203.
	Objective: To investigate whether systematic pelvic and para-aortic lymphadenectomy offers superior survival rates in patients with advanced epithelial ovarian cancer (EOC), tubal, or peritoneal cancer.; Methods: We searched the electronic databases PubMed (from 1996), Cochrane Central Register of Controlled trials (from 1996), and Scopus (from 2004) to September 2021. We considered randomised controlled trials (RCTs) comparing systematic pelvic and para-aortic lymphadenectomy with no lymphadenectomy in patients with advanced EOC. Primary outcomes were overall survival and progression-free survival. Secondary outcomes were peri-operative morbidity and operative mortality. The revised Cochrane tool for randomised trials (RoB 2 tool) was utilised for the risk of bias assessment in the included studies. We performed time-to-event and standard pairwise meta-analyses, as appropriate.; Results: Two RCTs with a total of 1074 patients were included in our review. Meta-analysis demonstrated similar overall survival (HR = 1.03, 95% CI [0.85-1.24]; low certainty) and progression-free survival (HR = 0.92, 95% CI [0.63-1.35]; very low certainty). Regarding peri-operative morbidity, systematic lymphadenectomy was associated with higher rates of lymphoedema and lymphocysts formation (RR = 7.31, 95% CI [1.89-28.20]; moderate certainty) and need for blood transfusion (RR = 1.17, 95% CI [1.06-1.29]; moderate certainty). No statistically significant differences were observed in regard to other peri-operative adverse events between the two arms.; Conclusions: Systematic pelvic and para-aortic lymphadenectomy is likely associated with similar overall survival and progression-free survival compared to no lymphadenectomy in optimally debulked patients with advanced EOC. Systematic lymphadenectomy is also associated with an increased risk for certain peri-operative adverse events. Further research needs to be conducted on whether we should abandon systematic lymphadenectomy in completely debulked patients during primary debulking surgery.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tzanis Alexander, A., et al. (2022). "Neoadjuvant Chemotherapy Versus Primary Debulking Surgery in FIGO Stage III and IV Epithelial Ovarian, Tubal or Peritoneal Cancer: A Systematic Review and Meta-Analysis." Oncology reviews 16: 10605.
	Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load. Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, peri-operative adverse events, and quality of life. Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86-1.07]) and progression-free survival (HR = 0.98, 95% CI [0.89-1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71-1.09]) nor for patients with metastatic lesions >5 cm (HR = 0.86, 95% CI [0.69-1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10 cm (HR = 0.94, 95% CI [0.78-1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48-3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16-0.72]. Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Tzanis, Iavazzo, Hadjivasilis, Tsouvali, Antoniou and Antoniou.)

Tzur, Y., et al. (2021). "Expectant Versus Medical Management of Retained Products of Conception after Induced Abortion." Journal of Minimally Invasive Gynecology 28(11): S106.
	Study Objective: To compare the efficacy of medical management versus expectant management of retained products of conception (RPOC) after first trimester medical abortion. Design: An open‐label randomized controlled trial. Setting: Academic tertiary‐care medical center. Patients or Participants: A total of 125 women who were diagnosed with RPOC 3 weeks after medical abortion by mifepristone and misoprostol. Sixty‐three were allocated to expectant management and 62 to medical management. Interventions: Recruited women were randomized into either expectant group or medical group (800 mcg misoprostol administered sublingually). RPOC was defined as a thick irregular endometrium (>12 mm) with positive Doppler flow. All women underwent repeat ultrasound scan every 2 weeks after randomization until a maximum of 6 weeks to rule‐out persistent RPOC. Women with persistent RPOC at the end of the 6‐week follow‐up (9 weeks from abortion) were referred to operative hysteroscopy. The primary outcome was the rate of women referred to operative hysteroscopy. Measurements and Main Results: There were no significant differences in demographic and clinical characteristics including age, BMI, nulliparity, smoking rates and mean gestational age at termination of pregnancy. The rate of women who were referred to operative hysteroscopy due to persistent RPOC was similar between the expectantly and medically managed groups (49.2% vs. 41.9%, respectively, P = 0.41). The mean RPOC thickness was similar between the expectant management and medical management groups (15±5.4 mm vs. 15±5.3 mm, respectively, P =.891). There was no difference in adverse outcomes between the two groups. Conclusion: Compared with expectant management, the administration of sublingual misoprostol in women diagnosed with RPOC after first trimester medical abortion does not reduce the need for operative hysteroscopy.

Ubinha, A. C. F., et al. (2024). "The Role of Pelvic Exenteration in Cervical Cancer: A Review of the Literature." Cancers 16(4): 817.
	Pelvic exenteration represents a radical procedure aimed at achieving complete tumor resection with negative margins. Although it is the only therapeutic option for some cases of advanced tumors, it is associated with several perioperative complications. We believe that careful patient selection is related to better oncologic outcomes and lower complication rates. The objectives of this review are to identify the most current indications for this intervention, suggest criteria for case selection, evaluate recommendations for perioperative care, and review oncologic outcomes and potential associated complications. To this end, an analysis of English language articles in PubMed was performed, searching for topics such as the indication for pelvic exenteration for recurrent gynecologic neoplasms selection of oncologic cases, the impact of tumor size and extent on oncologic outcomes, preoperative and postoperative surgical management, surgical complications, and outcomes of overall survival and recurrence-free survival.Copyright © 2024 by the authors.

UcakciAsalioglu, C. and S. YamanSozbir (2024). "Effect of online health training/counseling and progressive muscle relaxation exercise on postpartum depression and maternal attachment: A randomized controlled trial." International Journal of Gynecology and Obstetrics.
	Objective: To evaluate the effect of online health training/counseling and a progressive muscle relaxation exercise (PMRE) program on postpartum depression and maternal attachment. Method(s): The present study was a randomized, controlled, experimental trial. Participants were asked to complete the Prenatal Attachment Inventory (PAI) and the Edinburgh Postpartum Depression Scale (EPDS) at 35 weeks of pregnancy. Group assignment was done by stratified block randomization according to EPDS score (0-9, 10-30) and parity. Women in the experimental group received training in progressive muscle relaxation, postpartum depression, and maternal attachment via online video calls twice a week starting at 36-37 weeks of pregnancy. They were asked to complete the PMRE program from 36 weeks of pregnancy until 6 months postpartum, and online counseling was provided throughout this period. Participants completed the Maternal Postpartum Attachment Scale (MPAS) and the EPDS at 6 weeks postpartum. Result(s): Mean PAI score was 64.24 +/- 9.61 in the experimental group before the intervention and 62.14 +/- 10.13 in the control group. The mean EPDS score of the experimental group was 9.12 +/- 5.05 and the mean score of the control group was 9.77 +/- 6.30 (P > 0.05). The mean MPAS score after the intervention was 13.92 +/- 5.54 in the experimental group and 17.51 +/- 6.12 in the control group. The mean EPDS score of the experimental group was 3.40 +/- 3.00 and the mean score of the control group was 11.40 +/- 5.91 (P < 0.05). Conclusion(s): Online health training/counseling and PMRE reduce the risk of postpartum depression and increase maternal attachment.Copyright © 2024 International Federation of Gynecology and Obstetrics.

Uccella, S., et al. (2023). "Major vessel resection for complete cytoreduction in primary advanced and recurrent ovarian malignancies: A case series and systematic review of the literature - pushing the boundaries in oncovascular surgery." Gynecologic Oncology 179: 42-51.
	Introduction: Oncovascular surgery (the removal of major blood vessels infiltrated by cancer) is challenging but can be key to achieve complete cytoreduction in patient with advanced ovarian cancer. The aim of this study was to review the literature on oncovascular surgery in ovarian cancer and to report the details of all the cases performed at our institution.; Methods: We retrospectively reviewed the database of ovarian cancer patients who underwent debulking surgery at the Department of Obstetrics and Gynecology of Verona University between January 2021 and 2023. Patients with at least one major vessel resection during cytoreduction were identified. We then systematically review the literature searching Pubmed and Embase from inception to January 2023 to report all cases of surgery for ovarian cancer with concomitant major vessel resection.; Results: Five patients with advanced/recurrent ovarian cancer underwent major vascular resection at our institution. Vascular involvement was preoperatively identified in all cases and no case of vascular resection was performed after accidental injury. The major vessels removed were the inferior vena cava (n = 2), the common iliac veins (n = 2), the external iliac arteries (n = 2), the left common iliac artery (n = 1), and the left external iliac vein (n = 1). All patients underwent other non-gynecological cytoreductive procedures prior to vessel removal and had R0 obtained. Three (60%) patients experienced one or more postoperative complications. The literature search identified a total of seven cases of major vessels resection in ovarian cancer surgery. A single or multiple major vessels were removed in two (28.6%) and five (72.4%) cases, respectively. All the seven patients underwent vascular reconstruction. Four (57.1%) patients reported postoperative complications. Overall, 66.7% of the 12 total identified patients were free from disease at the last follow-up [median 15.5 months (range 5-25)].; Conclusions: Oncovascular surgery is feasible in selected patients with ovarian cancer, provided that a multidisciplinary approach with customized care is available.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Uccella, S., et al. (2020). "Laparotomy vs. minimally invasive surgery for ovarian cancer recurrence: a systematic review." Gland Surgery 9(4): 1130-1139.
	The objective of the present review is to thoroughly investigate the role of minimally invasive surgery (MIS) in the setting of secondary cytoreduction for ovarian cancer recurrence, comparing this approach to traditional open surgery. PubMed, ClinicalTrials.gov, Scopus and Web of Science databases (between 1st January 1989 and 1st January 2020), have been systematically queried to identify all articles reporting either laparoscopic or robotic-assisted secondary surgical cytoreduction for recurrent ovarian cancer. We also manually searched the reference lists of the identified studies. Only English language papers were considered. Two independent reviewers screened and identified the reports. A sub-analysis was performed including studies comparing MIS vs. open abdominal secondary cytoreduction. A total of 617 articles were considered. Among them, we included 12 retrospective studies on minimally invasive secondary cytoreduction, enrolling 372 patients (260 of whom were submitted to whether robotics or laparosopy). Three studies compared 69 patients who underwent MIS vs. 112 cases of open abdominal secondary cytoreduction. Other 9 articles described a total of 191 patients who had minimally invasive secondary cytoreduction for recurrent ovarian cancer without a comparative arm. The quality of the evidence was low. The decision regarding the use of MIS was left to surgeon's discretion; in general, the candidates to MIS were selected patients with single-site disease or few localizations of relapse. Compared to open surgery, MIS was associated with significantly lower blood loss, shorter hospital stay and less postoperative complications; the rate of complete cytoreduction to residual tumor =0 was 95.5% in MIS cases vs. 87.5% in laparotomy cases. The risk of complications was generally low. Disease-free and overall survival were comparable between groups. There is no consensus on the criteria to select patients for laparoscopic or robotic secondary cytoreduction. Intra-operative ultrasound has been proposed as a possible tool to better identify the site of recurrence and for confirmation of complete resection of disease. In conclusion, MIS is an option in selected patients with recurrent ovarian cancer, provided there is no widespread disease. Selection of patients appears of utmost importance to obtain satisfactory survival outcomes.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-353). The series “Ovarian Cancer Recurrence” was commissioned by the editorial office without any funding or sponsorship. SC serves as an unpaid editorial board member of Gland Surgery from Aug 2019 to Jul 2021 and served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare. (2020 Gland Surgery. All rights reserved.)

Uccella, S., et al. (2021). "Uterine artery closure at the origin vs at the uterus level in total laparoscopic hysterectomy: A randomized controlled trial." Acta Obstetricia et Gynecologica Scandinavica 100(10): 1840-1848.
	INTRODUCTION: The transfusion rate in hysterectomies for benign pathology is almost 3%. However, despite the strong interest in reducing intraoperative bleeding, limited evidence is available regarding the technical aspects concerning uterine vessel management during a total laparoscopic hysterectomy (TLH). Uterine artery (UA) closure in TLH can be performed at the origin from the internal iliac artery or at the uterus level (UL). However, low-quality evidence is available regarding the superiority of one method over the other. MATERIAL AND METHODS: We performed a single-blind randomized (1:1) controlled trial (NCT04156932) between December 2019 and August 2020. One hundred and eighty women undergoing TLH for benign gynecological diseases were randomized to TLH with UA closure at the origin from the internal iliac artery (n = 90), performed at the beginning of the procedure by putting two clips per side at the origin, vs closure at the UL (n = 90). Intraoperative blood loss estimated from suction devices was the primary outcome. Secondary end points were perioperative outcomes, the conversion rate from one technique to the other, and complication rates with 4 months of follow up. RESULTS: Uterine artery closure at the origin was completed in all 90 patients (0%), whereas closure at the UL was converted to closure at the origin in 11 cases (12.2%; p < 0.001); failures were mainly associated with the presence of endometriosis (81.8% [9/11] vs 10.1% [8/79]; p < 0.001). In the intention-to-treat analysis, the intraoperative blood loss was higher in the group assigned to the closure at the UL (108.5 mL) than in the group with closure at the origin (69.3 mL); the mean difference was 39.2 mL (95% CI 13.47-64.93 mL; p = 0.003). Other perioperative outcomes and complications rates did not differ. CONCLUSIONS: Uterine artery closure at the origin reduces intraoperative blood loss during a TLH and appears to be more reproducible than closure at the UL without higher complication rates. However, the absent translation in clinical benefits impedes the support of a clinical superiority in all women. Closure at the origin may provide clinical advantages in the presence of severe preoperative anemia or pelvic anatomic distortion.

Uccella, S., et al. (2020). "INCIDENCE AND PREVENTION OF VAGINAL CUFF DEHISCENCE FOLLOWING LAPAROSCOPIC AND ROBOTIC HYSTERECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS." Journal of Minimally Invasive Gynecology.
	OBJECTIVE: vaginal cuff dehiscence, a severe and potentially detrimental complication, has significantly increased following the introduction of endoscopic hysterectomy. The aim of the present systematic review and meta-analysis of the available literature is to identify the incidence and possible strategies to prevent this complication after total laparoscopic hysterectomy (TLH) and total robotic hysterectomy. DATA SOURCES: PubMed, ClinicalTrials.gov, Scopus and Web of Science databases have been systematically queried to identify all articles reporting either laparoscopic or robotic-assisted hysterectomies for benign indications in which vaginal dehiscence was reported as an outcome. Reference lists of the identified studies were manually searched. Only papers written in English were considered. METHODS OF STUDY SELECTION: The PICO (population, intervention, comparison, outcome) for the review include: (1: population of interest) women submitted to conventional and robotic-assisted laparoscopic hysterectomy; (2: interventions) possible methods to prevent vaginal dehiscence; (3: comparison) experimental strategies vs. standard of treatment or alternative strategy for each item of intervention; (4: outcome) rate of vaginal dehiscence. Series of subtotal hysterectomies and radical hysterectomies, as well as reports that combined both benign and malignant cases were excluded. The meta-analysis was performed using RevMan 5.4.1. Two independent reviewers identified all reports comparing two or more possible strategies to prevent vaginal dehiscence. TABULATION INTEGRATION AND RESULTS: a total of 401 articles were identified. Of these, 20 (6 randomized, 2 prospective, 12 retrospective) studies were included in the present review, for a total of 19392 patients. The incidence of vaginal dehiscence following TLH ranged between 0.64 and 1.35%. Robotic hysterectomy was associated with a risk of vaginal dehiscence of approximately 1.64%. No study compared early vs. delayed resumption of coital activity, nor analyzed the role of training in laparoscopic suturing. No study specifically assessed the impact of electrocautery on the risk of vaginal dehiscence in endoscopic hysterectomies for benign indications. Double-layer and reinforced sutures did not decrease the risk of dehiscence. Barbed sutures reduced the risk of separation compared to non-barbed closure [0.4% (4/1108) vs 2% (22/1097);(OR:0.25; 95% CI: 0.11-0.57)]. However, these data came mainly from retrospective series. Excluding studies on the use of self-anchoring sutures during robotic hysterectomy, there was no significant difference in the risk of dehiscence between barbed and non-barbed sutures 0.5% (4/890) vs. 1,4% 181/776); (OR,038; 95% CI: 0.13 - 1.10). Transvaginal suture of the vault at the end of an endoscopic hysterectomy appeared to increase the risk of dehiscence when compared to laparoscopic closure [2.3% (23/1002) vs. 1.16% (11/944);(OR:1.97; 95%CI: 1.00-3.88)]. CONCLUSION: there is a paucity of high-quality papers evaluating vaginal dehiscence and possible prevention strategies in the current literature. There are only two effective strategies identified in reducing the risk for this complication: the use of barbed suture and the adoption of a laparoscopic approach to close the vaginal cuff. When restricting the analysis only to laparoscopic cases, the use of barbed sutures does not protect against vaginal cuff separation.

Uccella, S., et al. (2019). "The role of sentinel node in early ovarian cancer: a systematic review." Minerva Medica 110(4): 358-366.
	Introduction: Early ovarian cancer (EOC) is defined as ovarian cancer macroscopically limited to the ovaries at the time of initial diagnosis. Approximately only 25% of patients with ovarian cancer are affected by EOC. This condition requires complete surgical staging, including systematic lymphadenectomy up to the level of the renal vessels, with the consequent risk of complications and morbidity. With the aim to reduce the procedure-related morbidity, sentinel lymph node mapping (SLNm) has been introduced as an experimental procedure in EOC staging. The aim of the present study is to systematically review the available series on this interesting issue.; Evidence Acquisition: Studies were identified by searching electronic databases. The search was systematically applied to PubMed, ClinicalTrials.gov, Scopus and Web of Science looking for records describing the use of sentinel lymph node technique in EOC from January 1st, 1989 to January 1st, 2019. A total of 10 studies were identified for inclusion. Of the 121 patients involved in these studies, only 43 had a histologically-confirmed diagnosis of EOC and were included in the present analysis.; Evidence Synthesis: SLN (paraaortic and/or pelvic) overall detection rate (DR) was of 97.6%. The overall sensitivity (SS) and negative predictive value (NPV) of the included cases were 66.7% and 96.6%, respectively. We calculated also NPV, SS and DR based on the anatomical lymph node district, with a value of 100% both in the lumbo-aortic and in the pelvic district and a DR of 83.3% and 43% respectively.; Conclusions: This review shows that evidence on SLNm in EOC is still scant. Based on the limited data available, SLNm may provide potentially useful information on nodal status in patients affected by this disease.

Uddandrao, V. V. S., et al. (2024). "Pathophysiology of obesity-related infertility and its prevention and treatment by potential phytotherapeutics." International Journal of Obesity 48(2): 147-165.
	Background: Obesity is a complex multifactorial disease in which the accumulation of excess body fat has adverse health effects, as it can increase the risk of several problems, including infertility, in both men and women. Obesity and infertility have risen together in recent years. Against this background, the present review aims to highlight the impact of obesity on infertility and the underlying pathophysiology of obesity-related infertility (ORI) in men and women, and to provide readers with knowledge of current trends in the effective development of phytotherapeutics for its treatment. Method(s): We thoroughly searched in PubMed, MEDLINE, Scopus, EMBASE, and Google Scholar to find all relevant papers on ORI and the therapeutic effects of phytotherapeutics on ORI in men and women. Result(s): The extensive search of the available literature revealed that obesity affects reproductive function through several complex mechanisms such as hyperlipidaemia, hyperinsulinaemia, hyperandrogenism, increased body mass index, disruption of the hormonal milieu, systemic inflammation, oxidative stress, alterations in epigenetics and dysbiosis. On the other hand, several studies reported that phytotherapeutics has a broad therapeutic spectrum of action by improving sex hormone homeostasis, ovarian dysfunction, menstrual cycle and inhibiting ovarian hyperplasia, as well as down-regulating ovarian apoptosis, inflammation and oxidative stress, and controlling metabolic dysfunction in obese women. Male infertility is also addressed by phytotherapeutics by suppressing lipogenesis, increasing testosterone, 3beta-HSD and 17beta-HSD levels, improving sperm parameters and attenuating testicular dyslipidaemia, oxidative stress, inflammation and germ cell apoptosis. Conclusion(s): In the present review, we discussed the effects of obesity on reproductive dysfunction in men and women and the underlying pathophysiology of ORI. In addition, the therapeutic effect of phytotherapeutics against ORI was highlighted. [Figure not available: see fulltext.]Copyright © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

Ugurlu, M., et al. (2024). "The effect of music on menopausal symptoms, sleep quality, and depression: a randomized controlled trial." Revista da Associacao Medica Brasileira 70(2): e20230829.
	OBJECTIVE: This study aimed to determine the effect of music on menopausal symptoms, sleep quality, and depression levels in menopausal women. METHOD(S): This randomized controlled study was carried out between August and December 2022. The study sample consisted of 61 menopausal women (intervention: 30 and control: 31). The intervention group listened to music twice a day for 5 weeks, with a total of 70 sessions. The control group received only routine care. Menopause symptoms, depression levels, and sleep quality were evaluated at the beginning and the end of the study using the Menopausal Symptoms Rating Scale, Beck Depression Inventory, and Pittsburg Sleep Quality Index. RESULT(S): The post-test Menopausal Symptoms Rating Scale, Beck Depression Inventory, and Pittsburg Sleep Quality Index scores of the menopausal women were found to be lower in the intervention group than in the control group (p=0.011, p=0.001, and p=0.006, respectively). When the pre-test and post-test mean scores were compared, the mean menopausal symptoms and depression levels decreased, and sleep quality increased significantly in the intervention group. No significant difference was observed in the control group. CONCLUSION(S): This study shows that music may have an effect on reducing the level of menopausal symptoms and depression levels and also increasing the sleep quality of menopausal women.Copyright © 2024 Associacao Medica Brasileira. All rights reserved.

Uguz, F. (2020). "Pharmacological prevention of mood episodes in women with bipolar disorder during the perinatal period: A systematic review of current literature." Asian Journal of Psychiatry 52.
	Objective: This review examined the efficacy of mood stabilizers and antipsychotics in patients with bipolar disorder during pregnancy and the postpartum period. Methods: PubMed was searched for reports between 01 January 1996 and 31 December 2019 by using combinations of key words bipolar disorder, pregnancy, postpartum period, puerperium, prophylaxis, mood stabilizers, antipsychotics, lithium, lamotrigine, valproate, carbamazepine, oxcarbazepine, olanzapine, risperidone, quetiapine, aripiprazole, haloperidol, and chlorpromazine. Results: The present reports included a total of 256 patients using lithium (n = 143), lamotrigine (n = 73), valproate (n = 17), olanzapine (n = 17), quetiapine (n = 4) and haloperidol (n = 1) during pregnancy or the postpartum period. Recurrence rates in pregnant patients using lithium (n = 79) and lamotrigine (n = 17) were 22.7 % and 41.2 %, respectively. According to very limited data, none of the patients using valproate (n = 2), quetiapine (n = 3) or olanzapine (n = 6) experienced a new episode during pregnancy. A recurrence was reported in 12 (70.6 %) of 17 patients using valproate during the postpartum period. The same recurrence rates in patients using lithium (n = 123), lamotrigine (n = 63), olanzapine (n = 17) and quetiapine (n = 3) were 20.3 %, 7.9 %, 11.7 %, and 33.3 %, respectively. Conclusions: This review suggests that lithium, lamotrigine and olanzapine seem to be effective in preventing new mood episodes in patients with bipolar disorder during the perinatal period. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Uhm, S., et al. (2022). "Mifepristone prior to osmotic dilators for dilation and evacuation cervical preparation: a randomized, double-blind, placebo-controlled pilot study." Contraception 107: 23‐28.
	OBJECTIVES: To evaluate mifepristone impact on osmotic dilator placement and procedural outcomes when given 18 to 24 hours before dilator placement for dilation and evacuation (D&E) at 18 weeks 0 days to 23 weeks 6 days gestation. STUDY DESIGN: We performed a randomized, double‐blind, placebo‐controlled trial from April 2019 through February 2021, enrolling participants undergoing osmotic dilator (Dilapan) placement for a planned, next‐day D&E. Participants took mifepristone 200 mg or placebo orally 18 to 24 hours before dilator placement. We used a gestational age‐based protocol for minimum number of dilators. Our primary outcome was the proportion of participants for whom 2 or more additional dilators could be placed compared to the minimum gestational age‐based standard. We secondarily evaluated cervical dilation after dilator removal in the operating room, subjective procedure ease, and complication rates (cervical laceration, uterine perforation, blood transfusion, infection, hospitalization, or extramural delivery). RESULTS: Of the planned 66 participants, we enrolled 44 (stopped due to coronavirus disease 2019‐related obstacles), and 41 (19 mifepristone; 22 placebo) completed the study. We placed 2 or more additional dilators compared to standard in 7 (36.8%) and 3 (13.6%) participants after mifepristone and placebo, respectively (p = 0.14). We measured greater median initial cervical dilation in the mifepristone (3.2 cm[2.6‐3.6]) compared to placebo (2.6 cm[2.2‐3.0]) group, p = 0.03. Surgeon's perception of procedure being "easy" (8/19[42.1] vs 9/22[40.9], respectively, p = 1.00) and complication rate (3/19[15.8%] vs 3/22[13.6], respectively, p = 1.00) did not differ. CONCLUSION: Our underpowered study did not demonstrate a difference in cervical dilator placement, but mifepristone 18 to 24 hours prior to dilators increases cervical dilation without increasing complications. IMPLICATIONS: Mifepristone 18 to 24 hours prior to cervical dilator placement may be a useful adjunct to cervical dilators based on increased cervical dilation at time of procedure; however, logistical barriers, such as an additional visit, may preclude routine adoption without definite clinical benefit.

Ujvari, D., et al. (2023). "Maternal serum levels of prokineticin-1 related to pregnancy complications and metformin use in women with polycystic ovary syndrome: a post hoc analysis of two prospective, randomised, placebo-controlled trials." BMJ Open 13(11): e073619.
	Objective: Serum prokineticin-1 (s-PROK1) in the second and third trimester of pregnancy is positively correlated to preeclampsia, intrauterine growth restriction (IUGR) and preterm delivery. Women with polycystic ovary syndrome (PCOS) are prone to these adverse pregnancy outcomes. However, the contribution of PROK1 to the development of pregnancy complications and the effect of metformin and hyperandrogenism on s-PROK1 in PCOS have not been studied previously.; Design: This work is a post hoc analysis of two prospective, randomised, placebo-controlled trials.; Setting: Pregnant women with PCOS were included from 11 study centres in Norway.; Participants: From 313 women, 264 participated in the present study after exclusions due to dropouts or insufficient serum samples.; Intervention: Women with PCOS were randomly administered with metformin or placebo, from first trimester to delivery.; Primary and Secondary Outcome Measures: s-PROK1 was analysed using ELISA at gestational week 19 and related to pregnancy complications, fasting insulin levels, homoeostatic model assessment for insulin resistance (HOMA-IR), testosterone, or androstenedione levels, metformin use, PCOS phenotype and hyperandrogenism.; Results: Maternal s-PROK1 in the second trimester did not predict pregnancy-induced hypertension, pre-eclampsia or late miscarriage/preterm delivery in women with PCOS. However, s-PROK1 was lower in women who used metformin before inclusion, both in those randomised to metformin and to placebo, compared with those who did not. s-PROK1 was also lower in those who used metformin both at conception and during pregnancy compared with those who used metformin from inclusion or did not use metformin at all. s-PROK1 was lower in hyperandrogenic compared with normo-androgenic women with PCOS.; Conclusions: Maternal s-PROK1 in the second trimester did not predict pregnancy complications in PCOS. Those who used metformin at conception and/or during pregnancy had lower s-PROK1. PCOS women with hyperandrogenism exhibited lower s-PROK1 compared with normo-adrogenic phenotypes.; Trial Registration Number: NCT03259919 and NCT00159536.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Umin (2021). "Development and effectiveness verification of the animation instruction for pelvic floor muscle exercises, featuring visualization." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Three‐month intervention for pelvic floor muscle exercises according to the leaflet instruction. Three‐month intervention for pelvic floor muscle exercises according to the developed animation instruction. CONDITION: Postpartum women PRIMARY OUTCOME: The following items before and after the intervention (at 3 months); Pelvic floor muscle strength; Presence or absence of pelvic floor muscle contraction; General Self‐efficacy Scale (GSES); Urinary incontinence: ICIQ‐SF (Japanese version) INCLUSION CRITERIA:

Umin (2021). "Effects of lactic acid bacteria intake on perimenopausal men and women on menopause-like symptoms, sleep and biomarkers." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Intake of test food for 8 consecutive weeks Intake of placebo food for 8 consecutive weeks CONDITION: Healthy adult PRIMARY OUTCOME: Questionnaire about menopause (KKSI or AMS) at 8 weeks ingestion SECONDARY OUTCOME: 1. Stiff shoulder VAS; 2. Pittsburgh Sleep Quality Index (PSQI‐j); 3. Cortisol; 4. DHEA‐S; 5. Hot flash INCLUSION CRITERIA:

Umin (2021). "Efficacy trial of 4 weeks ingestion of MSHF001 food." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Consumption of four MSHF001‐containing tablets per day (two tablets each after breakfast and before bedtime) for four weeks. Consumption of four placebo food tablets per day (two tablets each after breakfast and before bedtime) for four weeks. CONDITION: Healthy adults PRIMARY OUTCOME: Frequency of hot flashes SECONDARY OUTCOME: ‐Kupperman Kohnenki Shohgai Index (KKSI) ; ‐Menopause Symptom Assessment form; ‐WHO QOL26; ‐WHO‐5‐J; ‐The Brief Job Stress Questionnaire English version (B); ‐STAI; ‐OSA sleep inventory MA version INCLUSION CRITERIA:

Umin (2021). "A prospective study of the effects of Ninjin'yoeito on anemia and depressive symptoms in postpartum women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Kracie Ninjin&#39;yoeito, 7.5g per day, 4weeks Ferrous fumarate, 1cap per day, 4weeks CONDITION: Postpartum anemia PRIMARY OUTCOME: Change of hemoglobin levels, Prevalence of depressive symptoms as determined by the Edinburgh Postnatal Depression Scale(EPDS) SECONDARY OUTCOME: Change of fatigue(NRS) INCLUSION CRITERIA:

Umin (2022). "Effectiveness of anma massage therapy for lymphedema in survivors of gynecologic cancer." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Anma massage therapy + usual care for lymphedema (wearing an elastic stocking): A 60‐min whole‐body anma massage session administered once a week for 8 weeks (8 sessions in total). Sessions are followed by our anma massage protocol modified specifically for lymphedema. Usual care for lymphedema (wearing an elastic stocking) for 8 weeks. CONDITION: lymphedema PRIMARY OUTCOME: Lower limb circumference (five circumference measurements: from the head of the first metatarsal to head of the fifth metatarsal; at the ankle, from the lateral to medial malleolus; 5 cm below head of the fibula; 10 cm above the top of the patella; and at the thigh, at the point of the greater trochanter); We measure before and after the intervention/control duration, and also measure before and after each session. SECONDARY OUTCOME: 1) Quality of life, measured using a self‐administered questionnaire, the Japanese version of Quality of Life Measurement for Limb Lymphedema (J‐LYMQOL). ; 2) Blood flow velocity in the great saphenous vein, measured using a bidirectional vascular Doppler.; We measure before and after the intervention/control duration. INCLUSION CRITERIA:

Umin (2022). "The Effects of Clinical Pilates Exercises via Telerehabilitation on Menopausal Symptoms, Quality of Life, Depression and Anxiety in Postmenopausal Women During the COVID-19 Isolation Period." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: tele‐pilates group no tele‐pilates group CONDITION: almost done PRIMARY OUTCOME: quality of life INCLUSION CRITERIA:

Umin (2022). "Effects of self-care moxibustion for menstrual pain." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Self moxibustion Have the abdomen (Sekimoto) and lower legs (Saninko) use one each at home at least three times a week. No treatment follow‐up CONDITION: Menstrual pain PRIMARY OUTCOME: VAS SECONDARY OUTCOME: MDQ, HADS INCLUSION CRITERIA:

Umin (2022). "Investigation of the effect of pelvic floor muscle training using hip joint exercises on low back pain in postpartum women." International Clinical Trials Registry Platform (ICTRP).
	INTERVENTION: Pelvic floor exercises using hip muscle activity(2 times/day, 3 times/week for 6 weeks) Normal pelvic floor muscle exercises(2 times/day, 3 times/week for 6 weeks) CONDITION: Low back pain PRIMARY OUTCOME: Activity limitation due to low back pain (ODI) (pre, post 6w) SECONDARY OUTCOME: Bladder base elevation volume(ultrasound imaging); Continuous bladder base elevation time(ultrasound imaging); Vertical distance between pubococcygeal line and bladder neck/endocervical opening (MRI); Lumbar spine and hip angle during hip extension (accelerometer); Degree of low back pain (NRS); Pelvic floor muscle function (Female Pelvic Floor Deprivation Questionnaire); Adherence INCLUSION CRITERIA:

Unanyan, A., et al. (2021). "Efficacy of photodynamic therapy in women with HSIL and LSIL and early stage of squamous cervical cancer: a systematic review and meta-analysis." Photodiagnosis and photodynamic therapy 36: 102530.
	BACKGROUND: We sought to conduct a systematic review and meta-analysis of randomized and non-randomized clinical trials to assess the efficacy of photodynamic therapy (PDT) in cervical epithelial neoplasia (CIN) and early-stage cervical cancer. Additionally, according to the results, we tried to consider which stage of CIN is more sensitive/susceptible to PDT. METHODS: A systematic search was conducted using electronic databases including PubMed, ClinicalTrials.gov, the Cochrane Library, and Google Scholar. INCLUSION CRITERIA: all patients had confirmed low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or an early-stage cervical cancer - the cancer is less than 3 mm deep into the cervix -IA; type of photosensitizer and any type of wavelength. EXCLUSION CRITERIA: women who were previously treated with PDT; Risk of bias assessment was carried out for each study included in the systematic review using the Cochrane Handbook for Systematic Reviews of Interventions: RoB-2 was used to assess the risk of bias in randomized studies, while ROBINS-I - in non-randomized ones. RESULTS: We identified 2213 publications, but only 6 met the inclusion criteria and were included in the synthesis. PDT is most effective when patients have CIN 2 or photosensitizer is administered intravenously. CONCLUSION: Based on our systematic review and meta-analysis, it could be concluded that photodynamic therapy may be a practical approach in CIN (LSIL) regression compared with placebo. Nevertheless, we need more evidence and long-term follow-up to answer all questions thoroughly. OTHER: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. FUNDING: none. Declarations of interest: none. The present systematic review was registered in the PROSPERO international prospective register of systematic reviews by the National Institute for Health Research (NIHR). Protocol and registration number: PROSPERO 2021 CRD42021229141.

Undugodage Chithramali, H., et al. (2022). "Workplace based interventions to promote well being among menopausal women: a systematic review." PROSPERO International prospective register of systematic reviews.
	
Unger, J. M., et al. (2023). "Population, Clinical, and Scientific Impact of National Cancer Institute's National Clinical Trials Network Treatment Studies." Journal of Clinical Oncology 41(11): 2020-2028.
	PURPOSE In the United States, the National Cancer Institute National Cancer Clinical Trials Network (NCTN) groups have conducted publicly funded oncology research for 50 years. The combined impact of all adult network group trials has never been systematically examined.METHODSWe identified randomized, phase III trials from the adult NCTN groups, reported from 1980 onward, with statistically significant findings for >= 1 clinical, time-dependent outcomes. In the subset of trials in which the experimental arm improved overall survival, gains in population life-years were estimated by deriving trial-specific hazard functions and hazard ratios to estimate the experimental treatment benefit and then mapping this trial-level benefit onto the US cancer population using registry and life-table data. Scientific impact was based on citation data from Google Scholar. Federal investment costs per life-year gained were estimated. The results were derived through December 31, 2020.RESULTSOne hundred sixty-two trials comprised of 108,334 patients were analyzed, representing 29.8% (162/544) of trials conducted. The most common cancers included breast (34), gynecologic (28), and lung (14). The trials were cited 165,336 times (mean, 62.2 citations/trial/year); 87.7% of trials were cited in cancer care guidelines in favor of the recommended treatment. These studies were estimated to have generated 14.2 million (95% CI, 11.5 to 16.5 million) additional life-years to patients with cancer, with projected gains of 24.1 million (95% CI, 19.7 to 28.2 million) life-years by 2030. The federal investment cost per life-year gained through 2020 was $326 in US dollars.CONCLUSIONNCTN randomized trials have been widely cited and are routinely included in clinical guidelines. Moreover, their conduct has predicted substantial improvements in overall survival in the United States for patients with oncologic disease, suggesting they have contributed meaningfully to this nation's health. These findings demonstrate the critical role of government-sponsored research in extending the lives of patients with cancer.Copyright © American Society of Clinical Oncology.

Unicancer (2022). Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients With Metastatic Cancer in Response After 6 Months of Standard IO.
	No Results Available Drug: Reduced dose intensity of IO Progression-free survival (PFS)|Cost-effectiveness analysis of the proposed therapeutic strategy|Immune progression-free survival (iPFS)|Objective response rate (ORR)|Overall survival (OS)|Duration of response (DoR)|Quality of life questionnaire - Core 30 (QLQ-C30)|The Developed 5-level version of EQ-5D (EQ-5D-5L) questionnaire|Hospital anxiety and depression scale (HADS)|Fear of relapse questionnaire|Safety profile All Phase 3 646 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment UC-IMM-2101 March 7, 2025

Unit Nordic Society of Gynaecological Oncology - Clinical, T., et al. (2023). APX005M in Patients With Recurrent Ovarian Cancer.
	No Results Available Drug: APX005M Overall Response Rate according to RECIST at 12 weeks of treatment|Adverse events Female Phase 2 0 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment ENGOT-OV64/NSGO-CTU-SOLERO September 7, 2023

Univates, et al. (2023). Melatonin Use in Patients With Climacterious Symptoms in the Perimenopause.
	No Results Available Drug: Melatonin 3 MG Menopause rating scale|Beck Depression Inventory II|Pittsburgh Sleep Quality Index|Serum levels of S100β, TNF|6-sulfatoximelatonin urine levels|Visual Analog Pain Scale|Hamilton scale|Visual analogue scale of sleep Female Phase 2 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment 10901364 February 20, 2025

Universitesi Saglik, B. (2023). Effect of Lavender Inhalation on Dysmenorrhea.
	No Results Available Other: Lavender oil inhalation|Other: Placebo Dysmenorrhea Symptom Assessment Form|Numerical Pain Scale Female Not Applicable 51 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Supportive Care 16214662/050.01.04/130 May 15, 2024

University, A. (2022). The Effect of Laughter Yoga on the Stress Levels of Infertility Women.
	No Results Available Behavioral: Laughter Yoga Stress levels of women Female Not Applicable 90 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Supportive Care aslı14 June 30, 2024

University, A. (2023). Comparison of Different Massages Tecniques on Chronic Pelvic Pain.
	No Results Available Procedure: Thiele Massage|Procedure: Transverse Friction Massage Visual Analog Scale (VAS)|McGill Melzack Pain Questionnaire (MMPQ)|Notthingam Health Profile Questionnaire (NHP)|Female Sexual Function Index (FSFI)|Bristol Female Lower Urinary System Symptom Index (BFLUSSI) Female Not Applicable 20 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment SenaOndes1 March 31, 2023

University, A. and H. University (2023). Ethanol Sclerotherapy Prior to ART.
	No Results Available Procedure: Ethanol Sclerotherapy for Endometrioma Cumulative live birth rate|pain scores Female Not Applicable 84 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment AUTF April 1, 2025

University Ain, S. (2022). Hydroxychloroquine in Unexplained Recurrent Pregnancy Loss.
	No Results Available Drug: Hydroxychloroquine To investigate HCQ as a new edition in URPL protocol in change rate of pregnancy loss side by side with anticoagulant traditional treatment Female Phase 1 70 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Prevention HCQ in URPL January 2023

University Ankara Yildirim, B. (2022). The Effects Of Relaxation Training In Women With Primary Dysmenorrhea.
	No Results Available Other: Relaxation training|Other: No intervention Menstrual pain intensity|Menstrual symptoms|Impacts of academic/work performance|Impacts of life quality|Impacts of social activity|Anxiety level Female Not Applicable 30 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2022/04/07 December 15, 2022

University Artvin, C. (2023). Effects of Transcutaneous Vagus Nerve Stimulation (taVNS) in Individuals With Primary Dysmenorrhea.
	No Results Available Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)|Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Pain Intensity|Pain Pressure Threshold|Menstrual Symptom Scale (MSS)|Functional and Emotional Measure of Dysmenorrhea (FEMD)|Hamilton Anxiety Scale (HAM-A)|6-Minute Walk Test (6MWT)|Positive and Negative Affect Schedule (PANAS) Female Not Applicable 34 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment Vagus Nerve Stimulation January 30, 2024

University, B., et al. (2023). Treatment for Antepartum Posttraumatic Stress Disorder/PTSD Study.
	No Results Available Behavioral: Written Exposure Therapy (WET)|Behavioral: Emotion Focused Supportive Therapy (EFST) Clinician Administered Scale for PTSD-5 (CAPS-5) at baseline|Clinician Administered Scale for PTSD-5 (CAPS-5) at 8 weeks|Clinician Administered Scale for PTSD-5 (CAPS-5) at 1 month postpartum|Clinician Administered Scale for PTSD-5 (CAPS-5) at 6 months postpartum|Clinician Administered Scale for PTSD-5 (CAPS-5) at 12 months postpartum|PTSD Checklist for DSM-5 (PCL-5)|Patient Health Questionnaire (PHQ-9)|Depression, Anxiety, and Stress Scale (DASS-21) - Anxiety Scale only|Number of study sessions attended|Number of participants that completed all 5 study visits|Inventory of Psychosocial Functioning (IPF)|Postpartum Bonding Questionnaire (PBQ)|Client Satisfaction Questionnaire (CSQ-8) Female Not Applicable 240 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment H-42619|1R01HD107282-01A1 July 2027

University Bezmialem, V. (2023). Comparison of Recombinant Follicle Stimulating Hormone and the Combination of Recombinant Follicle Stimulating Hormone With Clomiphene Citrate in Stimulated Intrauterine Insemination Cycles.
	No Results Available Drug: Recombinant Follicle Stimulating Hormone|Drug: Recombinant Follicle Stimulating Hormone and Clomiphene Citrate Rate of clinical pregnancy|Rate of ongoing pregnancy Female Not Applicable 254 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 07.12.2022-E.87948 May 1, 2024

University Boise, S. (2024). Feasibility and Acceptability of a Telehealth Intervention Among Women With Perinatal Mental Health.
	No Results Available Behavioral: UPLIFT program Feasibility of Telehealth - Enrollment Number|Feasibility of Telehealth - Number of Sessions Attended|Feasibility of Telehealth - Drop out rate|Feasibility of Telehealth - Drop out pattern|Acceptability of Telehealth- Satisfaction/Feedback|Acceptability of Telehealth- Focus group|Preliminary data on treatment response- Edinburgh Postnatal Depression Scale (EPDS)|Preliminary data on treatment response- General Anxiety Disorder (GAD)-7|Preliminary data on treatment response- National Institute on Drug Abuse (NIDA) Quick Screen/Modified ASSIST Female Not Applicable 30 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Prevention bsu0307 January 22, 2025

University, C. (2021). Cukurova University Faculty of Medicine Non-interventional Clinical Research Institutional Ethics Committe.
	No Results Available Behavioral: Therapeutic Touch|Other: Sham Therapeutic Touch Sleep Quality|Fatigue Female Not Applicable 48 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care 09.07.2021/46 March 15, 2022

University, C. (2021). The Effectiveness of Relaxation Training on Primary Dysmenoreh and Menstrual Symptoms.
	No Results Available Other: relaxation techniques Visual Analogue Scale|menstrual symptom questionnaire Female Not Applicable 360 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care PrimDys01 December 31, 2021

University, C. (2022). Vaginal Dilator Therapy Among Women With Gynecologic and Breast Cancers Experiencing Dyspareunia.
	No Results Available Other: Vaginal Moisturizer|Device: Vaginal Dilator Difference in Mean Patient-Reported Pain Scores During Sexual Activity|Difference in Mean Patient-Reported Pain Scores During Speculum Exam Female Not Applicable 59 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care AAAT8915 February 29, 2024

University, C. (2023). Effect of Rapamycin in Ovarian Aging.
	No Results Available Drug: Rapamycin|Other: Placebo Measure of Ovarian Reserve|AMH level|Estradiol (E2) Level|FSH Level|Klotho Level Female Phase 2 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment AAAU1074 December 2024

University, C. and London (2023). Adaptive ChemoTherapy for Ovarian Cancer in Patients With Replased Platinum-sensitive High Grade Serous or High Grade Endometrioid Ovarian Cancer.
	No Results Available Drug: Carboplatin Modified Progression Free Survival (mPFS)|Acceptability (1/2)|Acceptability (2/2)|Deliverability (1/2)|Deliverability (2/2)|Compliance|Adverse events (1/2)|Adverse events (2/2)|Quality of life (1/2) - EORTC questionnaire (assessing the quality of life of patients with ovarian cancer)|Quality of life (2/2) - EQ-5D ((mobility, self-care, usual activities, pain/discomfort, anxiety/depression, a single summary index and a visual analogue scale)|Fear of progression|CA125|Further treatment (1/3)|Further treatment (2/3)|Further treatment (3/3)|Overall survival Female Phase 2 80 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 136618 November 1, 2027

University Celal, B. (2021). Effectiveness of Dark Chocolate and Music in Dysmenorrhea.
	No Results Available Behavioral: music|Dietary Supplement: Chocolate group Description of the students' demographics and clinical backgrounds.|To evaluate pain severity secondary to dysmenorrhea in the first day of menstruation through a Visual Analogue Scale (VAS).|To evaluate the effect of dark chocolate consumption in reducing the pain severity secondary to dysmenorrhea in the first day of menstruation through a Visual Analogue Scale (VAS).|To evaluate the effect of music consumption in reducing the pain severity secondary to dysmenorrhea in the first day of menstruation through a Visual Analogue Scale (VAS).|To evaluate anxiety level in the first day of first menstruation cycle through State Anxiety Inventory (SAI).|To evaluate the effect of dark chocolate consumption in reducing the anxiety level of students with dysmenorrhea using State-Trait Anxiety Inventory (STAI).|To evaluate the effect of the music in reducing the anxiety level of students with dysmenorrhea using State-Trait Anxiety Inventory (STAI). Female Not Applicable 84 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Prevention CelalBayar December 30, 2021

University, C. H. A., et al. (2022). Therapeutic Effect of Surgical Debulking of Metastatic Lymph Nodes in Cervical Cancer Stage IIICr.
	No Results Available Radiation: CCRT|Procedure: Surgical debulking of bulky or multiple lymph nodes PFS|OS|Treatment-related complications|False positive rate & positive predictive value of bulky or multiple LN imaging Female Not Applicable 234 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment KGOG1047_DEBULK March 31, 2029

University, D. (2022). The Effect of Web Based Education on the Level of Coping With Infertility Stress and Infertility Self-Efficacy.
	No Results Available Other: Web-based patient education for the intrauterine insemination (IUI) treatment process Infertility Stress Scale|Coping with the Infertility Stress Scale|Infertility Self-Efficacy Scale - Short Form Female Not Applicable 132 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care Duzce U|hilalkaradeniz1 December 30, 2022

University, D. (2022). Transcutaneous Electrical Nerve Stimulation During Outpatient Endometrial Biopsy.
	No Results Available Device: TENS 7000 Pain after Endometrial Biopsy, as measured by Visual Analogue Scale (VAS)|Number of participants who find the intervention acceptable based on survey response|Number of participants who find the intervention tolerable based on survey response|Change in Pain, as measured by Visual Analogue Scale (VAS) across different time intervals|Provider satisfaction with the procedure Female Not Applicable 149 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Care Provider)|Primary Purpose: Treatment Pro00111100 December 26, 2023

University Dublin, C., et al. (2022). Perioperative Exercise and Nutritional Optimisation Prehabilitation Before Surgery for Patients With Peritoneal Malignancy.
	No Results Available Behavioral: Exercise|Behavioral: Nutrition Feasibility of Adherence to the Intervention|Feasibility of participant retention to the Intervention|Feasibility of intervention effectiveness|Change in Cardiorespiratory Fitness|Change in Strength - The Handgrip Test|Change in Strength - The Stand to Sit Test|Change in Activity - 3-day ActivPAL3 triaxial accelerometer|Change in Psychological Stress|Change in Psychological Stress- Impact of Events Scale|Change in Cognitive Reserve-Cognitive Reserve Index (CR-IQ)|Change in Cognition- FACT-Cog|Change in Self-Efficacy|Change in Health Related Quality of Life (HrQoL)-EQ-5D-5L (5L)|Change in Health Related Quality of Life (HrQoL)- FACT-G|Change in Nutritional Status-The Malnutrition Screening Tool|Change in Nutritional Status- Glasgow Prognostic Score|Change in Dietary Intake - Foodbook24|Change in Nutritional Status- Blood Screening All Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Health Services Research COALESE/2021/103 June 1, 2024

University, E. (2023). Reiki & Premenstrual Syndrome & Quality of Life.
	No Results Available Other: reiki|Other: placebo Intensity of premenstrual symptoms evaluated using the Premenstrual Syndrome Scale|quality of life evaluated using the SF-36 Scale Female Not Applicable 90 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Supportive Care 23-4.1T/88 August 14, 2023

University Eastern, M. (2023). The Effect of Aromatherapy to Women With Vasomotor Complaints on Menopausal Quality of Life and Vasomotor Symptoms.
	No Results Available Other: placebo group|Other: mint oil group|Other: rose oil group VISUAL ANALOGUE SCALE (VAS)|Introductory Information Form|Hot Flashes Scale Specific to Menopause|Menopause-Specific Quality of Life Scale|Aromatherapy Form Female Not Applicable 66 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Supportive Care EasternMU-SBF-HB-GMAD-01 December 31, 2023

University, G. (2021). Online Postpartum Follow-up on Depression and Postpartum Adaptation.
	No Results Available Other: Online postpartum follow-up Postpartum depression|Postpartum adaptation Female Not Applicable 62 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 2020/93 September 28, 2021

University, G. (2022). Effect of Progressive Muscle Relaxation Exercise on Primary Dysmenorrhea Menstrual Symptoms and Quality of Life.
	No Results Available Behavioral: ROGRESSIVE MUSCLE RELAXATION EXERCISE change difference primary dysmenorrhea of the groups|change difference between the menstrual symptom scale scores of the groups Female Not Applicable 42 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 77082166 September 15, 2022

University, G. (2022). Transformatıonal Learnıng Theory on Infertılıty and Stigma in Infertılıty Women.
	No Results Available Other: EDUCATIONAL PROGRAM CREATED ACCORDING TO TRANSFORMATIONAL LEARNING THEORY change between the mean score of the Infertility Affected Scale of infertile women who participated in the training program created according to the transformative learning theory and who did not.|change between the mean score of the Infertility Stigma (Stigma) Scale of infertile women who participated and did not participate in the training program created according to the transformative learning theory. Female Not Applicable 52 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 77082166-604 June 15, 2023

University, G. (2023). Effect of Progressive Muscle Relaxation Exercises in Menopausal Women Experiencing RLS.
	No Results Available Behavioral: progressive muscle relaxation exercises Restless Legs Syndrome Severity|Quality of life associated with restless legs syndrome|Quality of sleep associated with restless legs syndrome Female Not Applicable 62 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment menopause May 30, 2024

University, G. and G. Region Vastra (2021). Transcutaneous Electrical Nerve Stimulation for Endometriosis-related Chronic Pain.
	No Results Available Device: Transcutaneous electrical nerve stimulation (TENS)|Other: Conventional analgesic treatment Pain intensity|Physical activity|Self-assessed physical activity|Consumption of analgetics|Change in pain intensity|Health Related Quality of Life (HRQL) according to SF36|Health Related Quality of Life (HRQL) assessed with EQ-5D|Health Related Quality of Life (HRQL) assessed with EHP 30|General Self-Efficacy Scale|Insomnia Severity|Days of sick-leave Female Not Applicable 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 274998 December 2025

University, H. (2023). Effects of Pelvic Floor Exercise Training in Postmenopausal Genitourinary Syndrome.
	No Results Available Other: Pelvic floor exercise training|Other: Patient/individual education vulvovaginal symptoms|urinary symptoms|Pelvic floor muscle function and strength|Pelvic floor muscle strength|The daily effect of vaginal aging|Urinary symptoms|Quality of life assessment Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2022/188 December 15, 2024

University, H. and Ghent (2021). Luteal Support in Artificial Vitrified/Warmed Cycles With Low Progesterone.
	No Results Available Drug: Progesteron TID Ongoing pregnancy rate|Endometrial impaction: Corelation between the change in endometrial thickness on day of embryo transfer and ongoing pregnancy rate Female Phase 3 242 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 2020-004112-10 January 1, 2025

University, H. and Ghent (2021). The Use of High Concentration Hyaluronic Acid (HA) Transfer Medium in Repeated Implantation Failure (RIF) Patients.
	No Results Available Drug: EmbryoGlue®, Vitrolife|Drug: Conventional Transfer Live birth|positive hCG|ongoing pregnancy rate Female Not Applicable 160 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Care Provider)|Primary Purpose: Treatment BC-08429 June 30, 2025

University, H., et al. (2022). Tinzaparin And Biomarkers After Neoadjuvant Treatment of Ovarian Cancer.
	No Results Available Drug: Tinzaparin Injectable Solution Changes in serum levels of CA-125 Changes in blood levels of hemoglobin Changes in blood levels of platelets|Changes in blood levels of leucocytes Changes in plasma levels of CRP Changes in plasma levels of albumin|Changes in plasma levels of interleukin 6 Changes in plasma levels of vascular endothelial growth factor|Self reported compliance to tinzaparin injections Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0 Objectively confirmed venous thromboembolism (VTE), i.e. pulmonary embolism, lower-limb deep vein thrombosis or upper extremity deep vein thrombosis. Death due to VTE. Female Phase 2 40 Other Allocation: Randomized|Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment The TABANETOC-trial|2021-000135-31 December 31, 2026

University, H. and Tours (2023). Health-Economic Evaluation of Early Diagnosis of Epithalial Ovarian Cancer Recurrence Using the ROMA Score: a Prospective Multicenter Randomized Trial.
	No Results Available Diagnostic Test: ROMA score evaluation Incremental Cost-Utility Ratio (ICUR) expressed as the cost per QALY gained at 36 months of using the ROMA score compared to usual follow-up with the CA-125 test, from the collective perspective.|Incremental Cost-Effectiveness Ratio (ICER) expressed as the cost per life-year gained at 36 months of using the ROMA score compared to usual follow-up with the CA-125 test, from the collective perspective.|Incremental Cost-Utility Ratio (ICUR) expressed as the cost per QAPFY gained at 36 months of using the ROMA score compared to usual follow-up with the CA-125 test, from the collective perspective.|Financial impact per year and over a 5-year period of spreading the use of the ROMA score in the routine follow-up of patients for the diagnosis of the first recurrence of epithelial ovarian cancer.|Characteristics of recurrence between the two groups (i.e. time to recurrence, location and operability)|Characteristics of treatments for first recurrence (including surgery)|Quality of life of women|Evolution of CA125, HE4 and ROMA score after management of the first recurrence|Estimation and validation of a mapping function from the specific EORTC QLQ-C30 and EORTC QLQ-OV28 questionnaires to the generic EQ-5D5L questionnaire. Female Not Applicable 320 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Diagnostic DR210313 November 2028

University, H. and H. University (2022). Effects of Connective Tissue Manipulation on Menopausal Symptoms.
	No Results Available Other: Connective tissue manipulation|Other: Superficial massage with the head of the therapeutic ultrasound device Frequency of vasomotor symptoms|Vasomotor symptom intensity|Severity of menopausal symptoms|Level of psychological symptoms|Severity of insomnia|Quality of life associated with menopause Female Not Applicable 52 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment 499 April 26, 2023

University, H., et al. (2022). SuJok Massage Dismenorea Painful Menstruation.
	No Results Available Behavioral: SuJok|Behavioral: Massage Menstrual Pain VAS|Affected by dysmenorrhea Female Not Applicable 120 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment SuJok August 30, 2023

University Hasan, K. (2023). The Effect of Mother-Baby Yoga Baby Perception, Maternal Attachment,Depression-Anxiety-Stress.
	No Results Available Behavioral: Mother Baby Yoga|Other: No intervention:control Fragile Infant Perception Scale|Maternal Attachment Scale|Depression, Anxiety, Stress Scale (DASS-21 All Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Prevention 2023/64 December 2, 2023

University Health, N. and Toronto (2021). A Study of Different Dosing Schedules of Selinexor in Sarcoma Patients.
	No Results Available Drug: Selinexor Incidence of toxicity and safety of Selinexor given on either a metronomic (Arm A) or split dosing (Arm B) schedule: Adverse Events|Recommended phase 2 dose of Selinexor given metronomically|Progression-Free Survival (PFS) of metronomic Selinexor|Objective Response Rate (ORR) of metronomic Selinexor|Clinical Benefit Rate (CBR) of metronomic Selinexor|Peak Plasma Concentration (Cmax) of metronomic Selinexor|Area under the plasma concentration versus time curve (AUC) of metronomic Selinexor|Characterization of the toxicity of metronomic Selinexor|Quality of life assessment using Quality of Life Questionnaire All Phase 1 56 Other Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment METSSAR February 2025

University Health, N. and Toronto (2024). Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium.
	No Results Available Drug: Ozempic|Drug: Mirena Complete Response Rate (CRR) at 6 months|CRR at 12 months: proportion of patients who achieve pathological complete response at 12 months after initiation of pIUD and semaglutide (%)|Time to achieve complete response: time it takes for the endometrium to return to normal (weeks)|Duration of response: duration of complete response (weeks)|Overall recurrence rate: proportion of patients who achieve pathological complete response but experience a recurrence (%)|Time to recurrence after complete response (weeks)|Overall progression/persistence rate: proportion of patients who experience progression or persistence (%)|Frequency of residual disease on definitive surgical specimens: proportion of patients with residual disease after they undergo completion hysterectomy (%)|Pregnancy rate (# of pregnancies/total attempting pregnancy)|Live birth rate (live births/total attempting pregnancy)|Incidence of Treatment-Emergent Adverse Events|Endometrial Cancer Specific Health Related Quality of Life Questionnaire (FACT-EN)|Impact of Weight on Quality of Life (IWQOL) scale|Generalized Anxiety Disorder 7-item (GAD-7) scale|Patient Health Questionnaire (PHQ-9) scale|Adapted Illness Intrusiveness Scale (IIRS)|Reproductive Concerns After Cancer (RCAC) scale Female Phase 2 90 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment WE-FiERCE January 2029

University, I. (2021). The Effect of Acupressure, Laughter Yoga and Mindfulness on Menopausal Symptoms and Quality of Life.
	No Results Available Other: Acupressure, laughter yoga and mindfulness stress reduction program Acupressure, Laughter Yoga and mindfulness stress reduction program Effects on menopause symptoms|Acupressure, Laughter Yoga and mindfulness stress reduction program Effects on menopausal quality of life Female Not Applicable 180 Other Allocation: Randomized|Intervention Model: Single Group Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care inonu university ethics May 2021

University, I. (2021). Foot Massage for Women With Menopause.
	No Results Available Other: Foot massage Sleep level in women with menopause|Fatigue level in women with menopause|Anxiety level in women with menopause Female Not Applicable 70 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 2021/2497 November 30, 2021

University, I. (2021). Therapeutic Touch and Music in The Menopausal Period.
	No Results Available Other: Therapeutic Touch|Other: Music Listening Group|Other: Control Group The effect of therapeutic touch on sleep quality|The effect of therapeutic touch on menopausal symptoms|The effect of therapeutic touch on quality of life|The effect of listening to music on sleep quality|The effect of listening to music on menopausal symptoms|The effect of listening to music on quality of life Female Not Applicable 108 Other Allocation: Randomized|Intervention Model: Sequential Assignment|Masking: Single (Care Provider)|Primary Purpose: Supportive Care menopause August 25, 2022

University, I. (2022). The Effect of Acupressure and Mindfulness to Cope With Premenstrual Syndrome (PMS) on PMS and Quality of Life.
	No Results Available Procedure: Acupresur|Procedure: Mindfulness|Procedure: Plasebo The Premenstrual Syndrome Scale (PMSS)|The World Health Organization Quality of Life Assessment Questionnaire Female Not Applicable 270 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care 2022/3172 March 15, 2023 The research was carried out to determine the effect of acupressure and mindfulness practice to cope with premenstrual syndrome on premenstrual symptoms and quality of life. The sample of the study consisted of a total of 270 students, 90 of which were acupressure, 90 mindfulness and 90 control groups. In the study, data were collected with the Participant Information Form, PMSS and WHOQOL-BREF. The acupressure group was asked to apply acupressure two days a week for 12 weeks, a total of 24 times. In the mindfulness group, 8 weeks of Conscious Awareness Stress Reduction Program was applied, after which the students were asked to practice mindfulness for 3 cycles. Students in both experimental groups were asked to stop the practices after acupressure and mindfulness practices. PMSS and WHOQOL-BREF were applied to both experimental and control groups as an intermediate test 12 weeks after the pre-test and a post-test 24 weeks later. Turkey

University, I. (2023). The Effects of Reiki on Menopausal Symptoms and Depression Levels.
	No Results Available Other: Reiki Menopause Rating Scale (MRS)|Beck Depression Inventory (BDI) Female Not Applicable 82 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care 2023/4577 July 23, 2023

University, I. (2023). Intraperitoneal Bupivacaine for Pelvic Organ Prolapse.
	No Results Available Drug: Bupivacaine|Other: Saline Pain score at 4 hours|Pain score at 8, 12, 24 hours|Total opiate consumption|Time to first narcotic|Hospital length of stay Female Phase 4 90 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 17120 January 1, 2025

University, I. (2023). Sacral Transcutaneous Electrical Stimulation Efficacy in Chronic Pelvic Pain: A Randomized Clinical Trial.
	No Results Available Device: Sham TENS Stimulation|Device: Sacral TENS Stimulation Visual Numeric Scale of Pain|The Pelvic Pain Impact Questionnaire|Female Sexual Function Index|Patient Satisfaction Questionnaire Female Not Applicable 38 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 2022/1719 September 15, 2023

University, I. and U. Cerrahpasa Istanbul (2022). The Effect of Stress Reduction Program on Pregnancy Process and Mental Health in High Risk Pregnant Women.
	No Results Available Behavioral: cognitive behavioral approach-based stress reduction program Information Form|Depression, Anxiety and Stress Scale (DASS-21)|Psychological Well-Being Scale :|Intolerance of uncertainty scale|Edinburgh Postnatal Depression Scale (EPDS)|Program Evaluation and Satisfaction Survey Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Care Provider)|Primary Purpose: Other IstanbulU-NKALYONCU-001 July 31, 2023

University, K. and R. Medicine Turkish Society of (2023). Outcomes of 36 vs 38 Hour Intervals From Ovulation Trigger To Oocyte Pick-Up:A Multi-Center Randomized Controlled Trial.
	No Results Available Other: 36-hour duration between ovulation triggering and oocyte pick-up procedure|Other: 38-hour duration between ovulation triggering and oocyte pick-up procedure Ratio of metaphase-2 oocytes to total number of follicles|Maturation rate|Fertilization rate|Cleavage rate|Blastulation rate|Premature ovulation rate|Positive Beta Human chorionic gonadotropin(Beta-hCG) test rate|Clinical pregnancy rate|Ongoing pregnancy rate|Live birth rate|Miscarriage rate|Biochemical pregnancy rate|Ectopic pregnancy rate Female Not Applicable 850 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 2021.267.IRB1.093 December 2025

University Kahramanmaras Sutcu, I. (2021). Analyse Of Early Skın To Skın Contact's Impact Upon Maternal-Infant Bondıng And Perceptıon Of Traumatıc Bırth.
	No Results Available Behavioral: skin-to-skin contact Maternal Attachment Scale Score|Traumatic Birth Perception Scale Score Female Not Applicable 350 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 10436591 November 25, 2022

University Kahramanmaras Sutcu, I. (2024). The Effect of Emotional Freedom Technique on Menopausal Symptoms, Quality of Life and Depression Level.
	No Results Available Behavioral: Emotional freedom technique group|Behavioral: Sham emotional freedom technique group Determining the level of perimenopausal depression|Determining quality of life|Assessment of menopausal symptoms|Determining the level of anxiety Female Not Applicable 105 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care KSUESRAKARATASOKYAY003 June 2024

University, K. T. O. K. (2021). "Electrical Stimulation in Women With Pelvic Organ Prolapse." ClinicalTrials.gov.
	No Results Available Device: Experimental|Device: Control The prolapse stage will be measured with Simplified POP-Q|Pelvic floor muscle strength will be measured measured with PFX Perineometer device(Cardio Design Pty Ltd, Australia)|The pelvic organ prolapse symptoms will be assessed by Pelvic Organ Prolapse Symptom Score(POP-SS).|The pelvic organ prolapse symptoms severity will be assessed by the Pelvic Floor Distress Inventory (PFDI-20) .|Patients' quality of life will be assessed using the Prolapse Quality of Life Scale (P-QOL).|Patients' sexual function will be assessed by the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-12 (PISQ-12) Female Not Applicable 26 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment KaratayZK February 1, 2022

University, K. T. O. K. (2022). Menoupausal Symptoms and Aromatherapy.
	No Results Available Other: Lemon oil|Other: peppermint oil|Other: Almond oil Menopause Symptoms Evaluation Scale Female Not Applicable 90 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Prevention Karatayhfz February 27, 2023

University, K. T. O. K. (2023). Effects of Aromatherapy Massage in Menopausal Women With Knee Osteoarthritis.
	No Results Available Other: Bergamot|Other: Placebo Change from baseline in pain at 4 weeks|Change from baseline in function at 4 weeks|Change from baseline in sleep quality at 4 weeks|Change from baseline in menopause symphtoms at 4 weeks|Patients satisfaction after the interventions Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Investigator)|Primary Purpose: Treatment KaratayUH8 August 13, 2023

University, M. (2021). The Effect of Acupressure Applied to Menopausal Women on Menopausal Symptoms and Quality of Life.
	No Results Available Other: Acupressure Menopause Rating Scale|World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) Female Not Applicable 61 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Investigator)|Primary Purpose: Supportive Care 701 November 15, 2021

University, M. (2021). The Effect of Acupressure on Menopausal Symptoms.
	No Results Available Behavioral: acupressure|Behavioral: Sham acupressure Menopause Rating Scale (MRS) Female Not Applicable 81 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care Mersin Univers March 21, 2022

University, M. (2021). The Effect of Yoga Practice on Pain Intensity, Menstruation Symptoms and Quality of Life in Primary Dysmenorrhea.
	No Results Available Other: Yoga Pain will evaluate using The The Short Form of the McGill Pain Questionnaire|Menstrual symptoms will evaluate using the Menstrual Symptom Questionnaire|Quality of life will evaluate using SF-36 Quality of Life Questionnaire Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Supportive Care MersinUni February 20, 2022

University, M. (2021). Online Peer-Delivered 1-Day CBT Workshops for PPD.
	No Results Available Behavioral: Online Peer-Delivered 1-Day CBT-Based Workshop Depression|Cost-Effectiveness - Costs|Cost-Effectiveness - Quality Adjusted Life Year|Anxiety|Mother-Infant Bonding|Social Support|Partner Relationship Quality|Parenting stress|Infant Temperament|Client Satisfaction Female Not Applicable 404 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Care Provider, Outcomes Assessor)|Primary Purpose: Treatment Peer1DayCBT February 18, 2022

University, M. (2021). The Role of Vitamin D Supplementation on Pain in Women With Primary Dysmenorrhea and Hypovitaminosis D.
	No Results Available Drug: Ergocalciferol Capsules|Drug: Placebo Visual analog pain scale Female Not Applicable 36 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 247/2021 April 30, 2023

University, M. (2022). Online 1-Day CBT-Based Workshops for Preventing Postpartum Depression.
	No Results Available Behavioral: Online 1-Day Cognitive Behavioural Therapy-Based Workshop EPDS score as a continuous outcome (Total EPDS) and an EPDS score of 13 or more at 2-months postpartum (T3) will serve as co-primary outcomes.|Maternal Anxiety (Generalized Anxiety Disorder 7-Item Scale (GAD-7))|Maternal Social Support (MSPSS)|Maternal Perceived Stress (Perceived Stress Scale (PSS))|Problems with the Mother-Infant Relationship (Postpartum Bonding Questionnaire (PBQ))|Infant Temperament (Infant Behaviour Questionnaire-Revised (IBQ-R)) Female Not Applicable 408 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Prevention RCT1-day CBT to prevent PPD March 10, 2025

University, M. (2022). Public Health Nurse-Delivered 1-Day CBT Workshops for PPD.
	No Results Available Behavioral: 1-Day Cognitive Behavioural Therapy-Based Workshop Edinburgh Postnatal Depression Scale (EPDS)|Generalized Anxiety Disorder 7-Item Scale|Multidimensional Scale of Perceived Social Support (MSPSS)|Parenting Stress Index (PSI-SF)|Postpartum Bonding Questionnaire (PBQ|Infant Behavior Questionnaire-Revised Very Short Form (IBQ-R)|EQ-5D-5L|Healthcare Resource Utilization Questionnaire|Mini International Neuropsychiatric Interview - Major Depressive Disorder Module|Mini International Neuropsychiatric Interview - Generalized Anxiety Disorder Module Female Not Applicable 447 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Investigator, Outcomes Assessor)|Primary Purpose: Treatment PHN1DayCBT October 31, 2024

University, M. (2023). The Effect of Acupressure on Pain, Menstrual Symptoms, and General Comfort in Adolescents With Primary Dysmenorrhea.
	No Results Available Other: Acupressure|Other: Placebo acupressure Visual Analog Scale (VAS)|Menstrual Symptom Questionnaire (MSQ)|General Comfort Scale (GAS) Female Not Applicable 52 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care 000 November 15, 2023

University, M., et al. (2023). Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI.
	No Results Available Drug: CP-506|Drug: Carboplatin|Drug: Immune checkpoint inhibitor Incidence of treatment-emergent adverse events including dose-limiting toxicities|Incidence of clinically significant abnormal measurements in physical examination, vital signs, electrocardiogram (ECG), lab tests and ECOG performance status|Area under curve of CP-506 plasma concentration|Determine the minimal biological effective dose|Objective Response Rate|Percentage change in tumour size All Phase 1|Phase 2 126 Other Allocation: Non-Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment TUMAGNOSTIC(CP506-001)|2021-000423-12|694812 May 2026

University, M. and O. Fertility (2023). Probiotic and Antibiotic Therapies in Women With Unexplained Infertility.
	The study is designed as a proof of concept pilot study with 3 study arms to evaluate the safety and feasibility of the use of oral probiotics and/or antibiotics in women with unexplained infertility/endometriosis. Our secondary outcomes will assess In Vitro Fertilization outcomes, and changes in the uterine microbiota (bacteria), intestinal barrier integrity, and urinary metabolites in response to study interventions.

University, N., et al. (2021). REDUCE Trial- Reducing Prolapse Recurrence.
	No Results Available Procedure: Posterior colpoperineorrhaphy Pelvic Organ Prolapse Quantification (POP-Q) System|Defecatory Dysfunction|Dyspareunia|Surgical and Perioperative Events: Blood Loss|Surgical and Perioperative Events: Operative Time|Surgical and Perioperative Events: Postoperative Pain|Surgical and Perioperative Events: Pain Medication Use Female Not Applicable 200 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment STU00214588 July 30, 2024

University, N., et al. (2022). My Wellbeing Guide: A Novel Tool for Managing Stress and Improving Quality of Life.
	No Results Available Behavioral: My Wellbeing Guide Change in depressive symptoms will be evaluated with the Patient-Reported Outcomes Measurement Information System Depression|Change in anxiety will be evaluated with the Patient-Reported Outcomes Measurement Information System Anxiety|Change in Health Related Quality of Life will be evaluated with The Functional Assessment of Cancer Therapy - General - 7 item version (FACT-G7) All Not Applicable 6516 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care STU00213537|1R37CA255875-01 June 1, 2028

University, N. and D. Seaweed (2023). 4-week Seaweed Supplementation on Menopause Symptoms and Psychological Wellbeing.
	No Results Available Dietary Supplement: 500mg seaweed|Other: Placebo The Menopause-Specific Quality of Life Questionnaire (Hildtich, 1996)|Centre for Epidemiologic Studies Depression Scale (Radlof, 1997)|The State-Trait Anxiety Inventory (Spielberger, 1983)|The Perceived Stress Scale (Cohen et al., 1983) Female Not Applicable 75 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Other Project ID 2434 December 20, 2023

University, N. and B. University (2022). Evaluating Technology Enabled Services in Perinatal Depression.
	No Results Available Behavioral: IntelliCare|Other: COMPASS-Care Depression|Anxiety|Satisfaction with care Female Not Applicable 75 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MH119029-RP2-RCT April 2024

University National, T. (2023). A Telehealth-delivered Physical Therapy Program for Postmenopausal Women With Urinary Incontinence.
	No Results Available Behavioral: Pelvic floor muscle training Number of participants consented to participate|Number of intervention sessions attended|Number of participants who remain in the study 3 months after baseline assessment|Number of participants who withdrew from the trial|Number of completed training sessions in relation to the scheduled sessions|Number of participants with intervention-related adverse events as assessed by CTCAE v4.0|Satisfaction scale|Acceptability scale|Weight|Height|Body mass index|Body fat percentage|Visceral fat level|Skeletal muscle percentage|Handgrip strength|Functional exercise capacity|Pelvic floor muscle strength|Bladder neck descent|Anteroposterior diameter of the urogenital levator hiatus|Anorectal angle|Severity of urinary incontinence|Physical activity levels Female Not Applicable 30 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment NSTC 112-2314-B-002-315- October 30, 2024

University Nottingham, T. (2023). Tackling Postnatal Depression: Culturally Adapted Learning Through Play Plus (LTP+) Intervention for British Mothers of African and Caribbean Origin.
	No Results Available Behavioral: Learning Through Play plus (LTP+)|Behavioral: Psychoeducation Change in postnatal depression is being assessed|Change in postnatal anxiety is being assessed|Change in social support is being assessed|Change in health-related quality of life is being assessed|Change in service satisfaction is being assessed|Change in child physio-emotional development is being assessed|Change in parenting knowledge of child development is being assessed Female Not Applicable 80 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Treatment 0000-0001-5034-0335b August 30, 2026

University Nottingham, T., et al. (2021). Online LTP+CaCBT for Treating Depression in British Mothers of African/Caribbean Heritage.
	No Results Available Behavioral: LTP|Behavioral: CaCBT|Behavioral: Psychoeducation Change in postnatal depression is being assessed|Change in postnatal anxiety is being assessed|Change in health is being assessed|Change in social support is being assessed|Change in health-related quality of life is being assessed|Change in service satisfaction is being assessed|Change in child physio-emotional development is being assessed|Change in parenting knowledge of child development is being assessed Female Not Applicable 120 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 0000-0001-5034-0335a August 30, 2023

University of, C. and Denver (2023). Parenting Skills Group for Mothers With Postpartum Depression.
	No Results Available Behavioral: Circle of Security Parenting program Change in methylation of OXTR receptor gene rs53576|Changes in Beck Depression Inventory, Second Edition (BDI-II) Score|Changes Postpartum Depression Screening Scale (PDSS) Score|Changes in Dyadic Adjustment Scale (DAS) Score|Changes in Denver Maternal Stress Assessment Score|Changes in MacArthur Short Form Vocabulary Checklist Score (child)|Changes in Maternal Postnatal Attachment Scale (MPAS) Score|Changes in The Multidimensional Scale of Perceived Social Support (MSPSS) Score|Changes in Carey Infant Temperament Questionnaire (ITQ) Score|Empathy & Theory of Mind Scale (EToMS) Score|Inventory of Callous-Unemotional Traits (ICU) Score Female Not Applicable 750 Other Allocation: Randomized|Intervention Model: Sequential Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 21-2593 June 1, 2035

University of, C. and Denver (2023). Role of Semaglutide in Restoring Ovulation in Youth and Adults With Polycystic Ovary Syndrome.
	No Results Available Drug: Wegovy Injectable Product|Drug: Metformin and Wegovy Rate of ovulation Female Phase 3 80 Other Allocation: Non-Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 21-4941 June 30, 2028

University of, C. and A. Los (2022). Transvaginal Electrical Stimulation for Myofascial Pelvic Pain.
	No Results Available Device: Urostym|Behavioral: Standard care Change of myofascial pelvic pain symptoms|Patient perception of treatment delivery by an LVN in comparison to specialist MD|Patient satisfaction with treatment delivery by an LVN in comparison to specialist MD|Benefit of therapy|Change in bothersome visceral bowel symptoms|Change in bothersome visceral bladder symptoms|Change in bothersome visceral sexual symptoms|Change in bothersome visceral genital symptoms|Change in pain severity|Change in pain features Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment Pending June 2023

University of, C., et al. (2023). Glucose Evaluation Through Continuous Glucose Monitors in Polycystic Ovary Syndrome.
	No Results Available Device: DEXCOM Continuous Glucose Monitor (CGM) Difference between change in hemoglobin A1C|Difference between change in fasting insulin Female Not Applicable 56 Other|Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 23-39852 July 2025

University of, C., et al. (2024). Prescription of Letrozole for Uterine Myoma.
	No Results Available Drug: Letrozole 2.5mg|Other: Placebo Change in fibroid symptom severity Female Phase 4 140 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 23-39255|R01HD112465 June 30, 2027

University of, M., et al. (2023). Rosie the Chatbot: Leveraging Automated and Personalized Health Information Communication.
	No Results Available Behavioral: Rosie the Chatbot Maternal postpartum depression|Number of emergency room visits|Attendance of well-baby visits (preventive healthcare visits) Female Not Applicable 400 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 5R01MD016037-03|3R01MD016037-03S1 June 30, 2026

University of North Carolina, C. H. and S. Therapeutics (2022). Effects Zulresso on Postpartum Psychosis.
	No Results Available Drug: Brexanolone Change in Positive and Negative Syndrome Scale (PANSS) score|Change in Young Mania Rating Scale (YMRS) score|Change in Hamilton Rating Scale for Depression (HAM-D)|Change in Edinburgh Postnatal Depression Scale (EPDS)|Change in Clinical Global Impression Scale (CGI) Female Early Phase 1 10 Other|Industry Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 20-0812 June 2024

University of, W. and Madison (2021). Massed and Spaced HMP App Dosage Study.
	This study is a randomized controlled trial (RCT) of 2 weeks of the Healthy Minds Program (HMP) app Connection module in undergraduate students of a large, midwestern state university in the United States during the spring of 2021. Participants will be recruited via email and/or flyers and will first complete an online screen. Eligible participants will complete baseline measures prior to attending an introductory session via web conferencing. During this session, participants will be randomly assigned to condition. Participants in both conditions will be asked to use the HMP app for 20 minutes per either, either split over two 10-minute session (Spaced condition) or in one 20-minute session (Massed condition). Participants will complete daily survey measures during the study and post-test measures after 2 weeks of intervention. This study is primarily designed to assess feasibility and acceptability of 2 weeks of Connection training and assignment to dosage condition. Study team will investigate self-reported informal practice on the daily diary measure, measures of psychological distress (composite of depression, anxiety) and loneliness.

University Ohio, S. (2021). A Randomized Controlled Trial of Treatment of Bacterial Vaginosis.
	Has Results Drug: Metronidazole|Drug: Placebo Evaluating Composite of Chorioamnionitis, Postpartum Endometritis, SSI, Wound Infection, or Other Post-cesarean Infections (Occurring Within 6 Weeks After Delivery)|Evaluating Incidence of Individual Infections.|Evaluating Incidence of Maternal Death|Evaluating Incidence of Puerperal Fever.|Evaluating Incidence of Use of Resources.|Evaluating Incidence of Adverse Events|Evaluating Incidence of Suspected Sepsis for Newborns|Evaluating Incidence of Confirmed Sepsis for Newborns|Evaluating Incidence of Newborn Intensive Care Unit (NICU) Admission and Duration|Evaluating Incidence of Neonatal Morbidities Female Phase 4 16 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment 2020H0476 February 9, 2022

University Ohio, S. (2024). The Mom and Infant Outcomes (MOMI) Study.
	No Results Available Behavioral: MOMI PODS|Behavioral: Enhanced Usual Care (EUC) Change in Life's Essential 8 (LE8) Composite Score|Change in Patient Health Questionnaire-9 (PHQ-9) Score|Change in Generalized Anxiety Disorder-7 (GAD-7) Score Female Not Applicable 384 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Prevention 2023H0305 May 30, 2028

University Ondokuz, M. (2022). Intrauterine Insemination and Nursing.
	No Results Available Device: Virtual Reality Glasses|Behavioral: Therapeutic Touch Spielberger State Anxiety Scale|Visual Analog Scale for pain intensity|Visual Analog Scale for patient satifaction Female Not Applicable 96 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care 2021/350 June 1, 2022

University Ondokuz, M. (2023). Symptom Management Program Based on Story Theory for Postmenopausal Women (SEMSTOP).
	No Results Available Other: SEMSTOP|Other: control The Pittsburgh Sleep Quality Index|Menopause Symptoms Rating Scale|Menopause Symptoms Rating Scale: Female Not Applicable 76 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Supportive Care 21063324 July 2023

University Penn, S. (2024). Thromboxane Function in Women With Endometriosis.
	No Results Available Drug: Aspirin|Other: Placebo blood pressure|heart rate|pain scale|skin blood flow Female Phase 4 96 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Single (Participant)|Primary Purpose: Basic Science 21851 August 1, 2027

University, Q. s. (2023). Investigating the Effectiveness of PelvicSense(R) on Pain and Sexual Outcomes in Endometriosis.
	No Results Available Behavioral: PelvicSense (R) Pain intensity|Pain catastrophizing Female Not Applicable 50 Other Allocation: N/A|Intervention Model: Single Group Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 379631-2 June 2025

University, S. (2021). Effects of High-frequency Deep Diathermy on Heart Rate Variability in Women With Primary Dysmenorrhea.
	No Results Available Device: High frequency therapy (5 minutes)|Device: High frequency therapy (7 minutes)|Device: High frequency therapy (9 minutes)|Device: Superficial heat therapy Heart Rate Variability Female Not Applicable 37 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Care Provider, Outcomes Assessor)|Primary Purpose: Treatment 2-1040781-A-N-012021046HR November 30, 2021

University, T. (2023). The Effect of Music Played to Newborn Mothers on Postpartum Blues.
	No Results Available Other: Music Postpartum blues evaluated using the Edinburgh Postpartum Depression Scale|Depression evaluated using the Stein Blues Scale Female Not Applicable 82 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Supportive Care 2023-03 January 18, 2024

University, T. (2023). Mother-infant Bonding in the Brain: a Mindfulness-based Intervention.
	No Results Available Behavioral: "Mindful with your Baby" group-based therapist-guided intervention|Behavioral: "Mindful with your baby" self-guided online intervention Change from baseline postpartum depressive symptoms|Change from baseline postpartum anxiety symptoms|Change from baseline parental stress|Change from baseline mother-infant bonding|Change from baseline neural synchrony between mother and infant (EEG outcome 1)|Change from baseline neural synchrony between mother and infant (EEG outcome 2)|Change from baseline postpartum-specific anxiety|Change from baseline worry|Change from baseline mindfulness skills|Change from baseline self-compassion|Change from baseline bonding|Change from baseline infant temperament|Change from baseline mindful parenting|Change from baseline parenting self-efficacy|Change from baseline personal goal Female Not Applicable 64 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 222-2022-166 August 2024

University Umm, A.-Q. (2021). Vitamin D Supplementation and Improvement of PCOS Therapy and IVF Outcomes in Infertile Saudi Women.
	No Results Available Drug: Vitamin D3|Drug: Clomiphene Citrate|Drug: Letrozole|Other: placebo Number of Participants with Clinical pregnancy|Number of Participants with live birth|Number of participants with Pregnancy loss rate|Number of participants with improved metabolic parameters Female Not Applicable 700 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment (AMSEC 82/1-4-2021) November 1, 2023

University Virginia, C. and N. Research National Institute of (2021). Mindful Moms Randomized Control Trial.
	No Results Available Behavioral: Mindful Moms|Behavioral: Prenatal Education Change in Depressive symptom severity|Change in anxiety|Change in stress Female Not Applicable 200 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment HM20021720|1R01NR020220 June 2026

University Wayne, S. (2021). Treatment of Intrapartum Depression Using Non-invasive Photobiomodulation.
	No Results Available Radiation: Delivery of infrared light to the head|Other: No Infrared treatment Change in depression score|Alteration in brain metabolism Female Not Applicable 80 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment IRB 20-05-2295 September 1, 2022

University, Y. (2021). Catheter-directed Sclerotherapy Versus Surgical Resecction: Randomized Controlled Trial Comparing Ovarian Function and Therapeutic Efficacy After Treatment of Ovarian Endometrioma.
	No Results Available Procedure: catheter-directed sclerotherapy|Procedure: surgical resection Serum AMH|Recurrence|hospital stay|serum CA-125|EHP-30 (Endometriosis Health Profile-30) Female Not Applicable 98 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 4-2021-1512 December 17, 2023

University, Y. (2024). A Three-arm Randomized Phase II Study of Dostarlimab Alone or With Bevacizumab Versus Nonplatinum Chemotherapy in Recurrent Gynecological Clear Cell Carcinoma: DOVE (APGOT-OV7/ ENGOT-ov80 Study).
	No Results Available Drug: Dostarlimab|Drug: Bevacizumab|Drug: Doxorubicin|Drug: Gemcitabine|Drug: Paclitaxel|Drug: Pegylated liposomal doxorubicin Progression Free Survival|Objective Response Rate|Disease control rate|Clinical benefit rate|Progression Free Survival 2|Overall survival|Duration of Response Rate|Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]|Time to first and second Subsequent Treatment|Response rate of subsequent therapies Female Phase 2 198 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment 4-2023-0794 December 31, 2029

University, Y., et al. (2023). FRIEND: Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea.
	No Results Available Drug: Green Tea Extract|Other: Placebo Cumulative live birth rate.|The conception rate|The miscarriage rate|The change of fibroid volume|The change of fibroid symptom severity score|The change of health-related quality-of-life questionnaire score|Time to conception Female Phase 3 200 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment IRB00215624|1R01HD100369 September 30, 2024

University, Y., et al. (2022). Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis.
	No Results Available Drug: Elagolix 200 MG|Other: Placebo or SOC IVF Live birth rate|Fertilization rate|Number of embryos transferred|Implantation rate|Biochemical pregnancy rate|Clinical pregnancy rate|Miscarriage rate|Overall pregnancy complication rate|Gestation age at delivery|Infant birth weight Female Phase 3 400 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Treatment 2000027121|1R01HD100336-01 September 30, 2024

Unno, H., et al. (2020). "Development of lymphangiosarcoma after pelvic radiation therapy for uterine cervical cancer: A case report and literature review." Eur. J. Gynaecol. Oncol. 41(3): 326-331.
	
Upadhyay, S., et al. (2023). "A comparative analysis of phytochemicals versus synthetic drugs/nanomedicines in the treatment of uterine fibroid: a systematic review." Toxicology and Environmental Health Sciences.
	Most women experience uterine fibroids (UFs), a common benign gynecological tumor, at some point in their reproductive age. There are several pharmacological treatments available to shrink fibroids and lessen the UF symptoms. These medications cost a lot of money, though, and frequently have serious side effects. Therefore, due to their low cost, comparable and powerful therapeutic efficiency and lower side effects, phytochemical-based medications are gaining popularity in these days. This review's goal is to provide a summary of the knowledge that is currently unavailable regarding the mechanisms of the action of various phytochemical-based medications with anti-uterine fibroid efficacy. The present results showed that dietary phytocompounds (dehydroxyelephantopin, butein, capsaicin, fisetin, kaempferol, resveratrol, silibinin and curcumin) could probably be effective as therapeutic compounds for uterine leiomyoma. These phytochemicals indicated their capability to regulate main fibroid promoting and initiating events for instance, proliferation, inflammation, angiogenesis and fibrosis in various experimental setups through modulating various signaling pathways, such as Smad 2/3, PI3K/AKT/mTOR, ERK 1/2 and beta-catenin indicating that they could serve as targets for prevention and/or treatment of UFs. This review provides key molecular insights for the development of phytochemical-based novel personalized therapy for non-surgical management of UFs which may help to avoid hysterectomy.Copyright © 2023, The Author(s), under exclusive licence to Korean Society of Environmental Risk Assessment and Health Science.

Uphoff, E. P., et al. (2022). "Mental health promotion and protection relating to key life events and transitions in adulthood: a rapid systematic review of systematic reviews." Journal of Mental Health.
	Background: During the decades representing working-age adulthood, most people will experience one or several significant life events or transitions. These may present a challenge to mental health. Aim(s): The primary aim of this rapid systematic review of systematic reviews was to summarise available evidence on the effectiveness of interventions to promote and protect mental health relating to four key life events and transitions: pregnancy and early parenthood, bereavement, unemployment, and housing problems. This review was conducted to inform UK national policy on mental health support. Method(s): We searched key databases for systematic reviews of interventions for working-age adults (19 to 64 years old) who had experienced or were at risk of experiencing one of four key life events. Titles and abstracts were screened by two reviewers in duplicate, as were full-text manuscripts of relevant records. We assessed the quality of included reviews and extracted data on the characteristics of each literature review. We prioritised high quality, recent systematic reviews for more detailed data extraction and synthesis. Result(s): The search and screening of 3997 titles/abstracts and 239 full-text papers resulted in 134 relevant studies, 68 of which were included in a narrative synthesis. Evidence was strongest and of the highest quality for interventions to support women during pregnancy and after childbirth. For example, we found benefits of physical activity and psychological therapy for outcomes relating to mental health after birth. There was high quality evidence of positive effects of online bereavement interventions and psychological interventions on symptoms of grief, post-traumatic stress, and depression. Evidence was inconclusive and of lower quality for a range of other bereavement interventions, unemployment support interventions, and housing interventions. Conclusion(s): Whilst evidence based mental health prevention and promotion is available during pregnancy and early parenthood and for bereavement, it is unclear how best to support adults experiencing job loss, unemployment, and housing problems.Copyright © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Urbana-Champaign University of Illinois, a., et al. (2023). Mindfulness to Reduce Post-cesarean Pain and Prevent Postpartum Depression.
	No Results Available Behavioral: Mindfulness Postpartum depression|Post-operative pain Female Not Applicable 75 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MaMiDaPP March 31, 2026

Ursache, A., et al. (2024). "Vitamin D-The Iceberg in Endometriosis-Review and Meta-Analysis." Journal of Personalized Medicine 14(1): 119.
	(1) Background: Although vitamin D has many known biological effects, very little research has been conducted on how vitamin D may be related or play a role in endometriosis. The aim of our study was to perform an evaluation regarding vitamin D levels and possible implications in endometriosis through a statistical analysis of the data collected from the included studies. (2) Methods: For this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed/Internet portal of the National Library of Medicine databases using several keywords related to our topic. (3) Results: Only nine articles were identified as complete or possessing the capacity to compute all available data. We totalized a number of 976 patients with endometriosis and 674 controls. From the nine studies included in our analysis, three of them claim there is no difference between women with and without endometriosis concerning 25(OH) vitamin D levels; however, the other six studies found significant differences regarding this aspect. (4) Conclusion(s): Our results underscored the complexity of analyzing the role of the vitamin D complex in a challenging condition like endometriosis and suggest that focusing on the tissue level might be essential to obtain accurate answers to our inquiries.Copyright © 2024 by the authors.

Utah University, o. (2023). Using Reiki Therapy to Improve Symptoms Associated With Brachytherapy in Patients With Gynecological Malignancies.
	No Results Available Other: Reiki therapy Comparison between the treatment groups of the change in anxiety from Assessment 1 to Assessment 3 as measured by the 6-item Spielberger State Anxiety Scale.|Comparison between the treatment groups of the change in pain from Assessment 1 to Assessment 3 as measured by the Visual Analog Scale - Pain.|Comparison between the treatment groups of the change in anxiety from Assessment 2 to Assessment 3 as measured by the 6-item Spielberger State Anxiety Scale.|Comparison between the treatment groups of the change in anxiety from Assessment 1 to Assessment 3 as measured by the Visual Analog Scale - Pain.|Comparison between the treatment groups of the change in state anxiety and depression from Assessment 1 to three month post-radiation as measured by the Hospital Anxiety and Depression Scale. Female Phase 2 68 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment HCI158391 April 1, 2027

Utian, W., et al. (2024). "The Effect of Estetrol (E4) on Patient-Reported Outcome Measures in Postmenopausal Women - Results From a Phase 3 Trial." Journal of Neurosurgical Anesthesiology 36(1): 1302.
	Objective: Estetrol (E4) is a native estrogen in development for menopausal vasomotor symptoms (VMS) in postmenopausal (PM) women. A previous phase 2 trial found that E4 was effective for the treatment of VMS, genitourinary syndrome of menopause (GSM) symptoms and quality of life (QoL), with a favorable safety profile. Moreover, E4 had minimal impact on hemostasis and had potentially beneficial effects on lipids, carbohydrate metabolism, and bone turnover. Data from two Phase 3 trials demonstrated a significant reduction in the frequency and severity of moderate to severe VMS. Here, we present the patient-reported outcomes from a Phase 3 trial (E4Comfort 1), which was conducted at 151 enrolling sites in 14 countries in Europe, Latin America, Russia, and North America. Design(s): In this randomized, placebo-controlled, doubleblind phase 3 trial, 640 PM women 40-65 years of age were randomized to receive E4 15 mg (n=213), E4 20 mg (n=213), or placebo (n=214) daily for 12 weeks. To ensure endometrial protection all non-hysterectomized (NH) women received progesterone 200 mg once daily for 14 days after completion of E4 treatment. Secondary efficacy endpoints including QoL, clinical meaningfulness, and GSM symptoms were measured by validated patient-reported outcome questionnaires. For QoL, the Menopause-Specific Quality of Life (MENQOL) questionnaire was completed at baseline and at week 12 and consisted of 29 items: vasomotor (3 items), psychosocial (7 items), physical (16 items), and sexual (3 items). Items pertaining to a specific symptom were rated as present or not present, and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. The Clinical Global Impression questionnaire was completed at baseline and at weeks 4 and 12 to evaluate clinical meaningfulness of VMS reduction. Participants answered the following question: Rate the total improvement, whether or not in your judgment it is due entirely to drug treatment. Compared to your condition at admission to the study, how much has it changed? Potential responses included very much improved , much improved , minimally improved, no change, minimally worse, much worse, or very much worse. Very much improved and much improved were included in the rating of clinical important (meaningful) difference. GSM symptoms were self-assessed at baseline and at week 12 and involved vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity (dyspareunia) (scored as 0 [none], 1 [mild], 2 [moderate], or 3 [severe]), and vaginal bleeding associated with sexual activity (scored as 0 [absent] or 1 [present]). Statistical analyses on changes from baseline were performed using analysis of covariance. Result(s): Significant improvements at week 12 versus placebo were found in the total MENQOL score and in the vasomotor, psychosocial, and sexual functioning domain scores after E4 15 mg and E4 20 mg treatment, and in the physical domain score after E4 20 mg treatment (p<0.05). A significantly higher percentage of participants rated their condition as much improved or very much improved compared with baseline regarding the weekly frequency of moderate to severe VMS in the E4 15 mg (52.9% and 73.3%) and E4 20 mg (59.8% and 77.8%) groups versus placebo (27.9% and 47.0%) at weeks 4 and 12, respectively (p<0.0001). GSM symptoms numerically decreased in all treatment groups after 12 weeks of treatment. A significant treatment effect was observed with E4 15 mg compared to placebo at week 12 with a reduction in least square mean difference versus baseline in vaginal pain associated with sexual activity (-0.23 [95% confidence interval [CI]: -0.41, -0.04]; p=0.0142) and vaginal dryness (-0.31 [95% CI: -0.53, -0.09]; p=0.0030). Conclusion(s): E4 demonstrated beneficial effects on QoL and GSM symptoms and provided clinically meaningful improvements in postmenopausal women with moderate to severe VMS.

Utian, W., et al. (2024). "Estetrol (E4), a Promising New Treatment for Menopausal Vasomotor Symptoms: Beneficial Lipid and Carbohydrate Metabolism in a Phase 3 Randomized, Double-blind, Placebo-Controlled Trial." Journal of Neurosurgical Anesthesiology 36(1): 1259.
	Objective: Estetrol (E4) is a native estrogen in development for menopausal vasomotor symptoms (VMS) in postmenopausal (PM) women. A previous phase 2 trial found that E4 was effective for the treatment of VMS, genitourinary syndrome of menopause symptoms and quality of life, with a favorable safety profile. Moreover, E4 had minimal impact on hemostasis and had potentially beneficial effects on lipids, carbohydrate metabolism, and bone turnover. Data from two Phase 3 trials demonstrated a significant reduction in the frequency and severity of moderate to severe VMS. Here, we present the results on lipid and carbohydrate metabolism from a Phase 3 trial (E4Comfort I), which was conducted at 151 enrolling sites in 14 countries in Europe, Latin America, Russia, and North America. Design(s): In this randomized, placebo-controlled, double-blind phase 3 trial, 640 postmenopausal women 40-65 years of age were randomized to receive E4 15 mg (n=213), E4 20 mg (n=213), or placebo (n=214) daily for 12 weeks. To ensure endometrial protection all non-hysterectomized women received progesterone 200 mg once daily for 14 days after completion of E4 treatment. Beside the primary VMS efficacy objective, the impact on lipid and carbohydrate metabolism was assessed, for which blood samples were taken at baseline and at Week 12 (W12). Lipid parameters included total cholesterol (total C), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total C/HDL-C ratio, triglycerides (TG) and lipoprotein (a). Parameters for carbohydrate metabolism included fasting plasma glucose, insulin, glycated hemoglobin (HbA1c) and homeostasis model-assessment-estimated insulin resistance (HOMA-IR). Samples were analyzed by a central laboratory. Mean and mean change from baseline to W12 were calculated and statistical analyses on changes from baseline to week 12 were performed using ANCOVA. Result(s): Statistically significant changes (p<0.05) from baseline at W12 were observed for cholesterol/HDL ratio (decrease), HDL-C (increase), and lipoprotein (a) (decrease) for both E4 15 mg and E4 20 mg compared to placebo. Statistically significant decreases in LDL-C and increases in TGs were observed only for E4 15 mg compared to placebo. TGs were numerically increased with E4 20 mg, but this was not statistically different from placebo. Reductions in fasting plasma glucose and HbA1c from baseline to Week 12 were statistically significant with E4 15 mg and E4 20 mg compared to placebo. Decreases in insulin levels and HOMA-IR for the E4 treatment arms compared to the placebo arm did not reach statistical significance. Conclusion(s): 12-week treatment with E4 15 mg and E4 20 mg resulted in beneficial effects on the lipid profile with an increase in HDL-C and a decrease in total C/HDL-C ratio, LDL-C and lipoprotein (a). Beneficial effects were also seen on carbohydrate metabolism with a decrease in fasting plasma glucose and in HbA1c associated with an obvious trend to decrease in insulin and HOMA-IR.

Utian, W., et al. (2022). "Efficacy and Safety of Estetrol (E4), a Promising New Treatment for Menopausal Vasomotor Symptoms: Results of Two Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial." Menopause 29(12): 1454.
	Objective: Estetrol (E4) is a native estrogen produced by the human fetal liver. Like other estrogens, E4 binds and activates the nuclear estrogen receptor alpha (ERalpha) and recruits the same coregulators. Unlike other estrogens, E4 induces limited activity on membrane ERalpha in several tissues including the breast and antagonizes this pathway in the presence of estradiol. E4 and selective estrogen receptor modulators (SERMs) do not recruit the same coregulators and therefore E4 is considered the first Native Estrogen with Selective Tissue activity (NEST). Data in pre- and postmenopausal women has shown that E4 alone or in combination with a progestin has minimal stimulatory effects on triglycerides, sex hormone binding globulin, and angiotensinogen. E4 also had minimal effects on clinically relevant hemostasis markers that are used as markers of risk of venous thromboembolism. A multicenter, randomized, placebo-controlled, double-blinded, dose-finding phase 2 study including 257 postmenopausal women aged 40 to 65 years found that E4 was effective for the treatment of menopausal vasomotor symptoms (VMS), genitourinary symptoms, and quality of life, with a favorable safety profile. Here, we present the first top line efficacy results from two Phase 3 trials on the use of E4 for the treatment of moderate to severe VMS in postmenopausal women. The trials were conducted in Europe, Latin America, Russia, and North America (USA and Canada) (E4Comfort I and II studies). Design(s): The E4Comfort studies were two placebocontrolled, double-blind, multicenter, randomized trials that evaluated the efficacy and safety of E4 for the treatment of moderate to severe VMS in postmenopausal women age 40 to 65 years. Included were hysterectomized (H) or non-hysterectomized (NH) subjects with >=7 daily or >=50 moderate to severe bothersome VMS in the week before randomization. Subjects were randomized to one of three arms (E4 15 mg, E4 20 mg, or placebo) in a 1:1:1 ratio and received study drug for 12 weeks (efficacy part; n=200 per arm). Efficacy was measured by the mean change from baseline in the frequency and severity of moderate to severe VMS at week 4 and week 12 compared to placebo based on the daily diary reports (co-primary endpoints). The studies were designed to assess the general and endometrial safety with up to 12 months of treatment with E4 15 and 20 mg (H and NH women; E4Comfort II) or with E4 20 mg in combination with progesterone 100 mg (NH women; E4 Comfort I). Result(s): Both studies met all four co-primary endpoints. Compared to placebo, there was a significant reduction in the frequency (up to 80%) and severity (up to 56%) of moderate to severe VMS at week 4 and week 12 (p<0.05). At week 12, E4 had a positive effect on quality of life (mood swings, anxiety, sleep, joint pain, libido, skin and hair quality) based on a secondary endpoint evaluation in the E4Comfort I study. Conclusion(s): E4 is effective at decreasing vasomotor symptoms in postmenopausal women. With the expectation that E4's good safety profile will be confirmed in the E4Comfort I and II studies, E4 will offer a novel treatment option for symptomatic postmenopausal women.

Utrecht, U. M. C. (2022). Luteal Phase Support in IUI MOH Treatment Luteal Phase Support in IUI MOH Treatment.
	No Results Available Drug: Progesterone Vaginal Product|Drug: Placebo Live Birth|Clinical pregnancy rate|Miscarriage rate|Multiple pregnancy rate|Pregnancy complications|Perinatal outcomes|Side effects|Compliance to therapy|Added medication costs|Budget impact Female Phase 4 1008 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 2359660 August 2026

Uzunlar, O., et al. (2021). "Technique to reduce blood loss during open abdominal myomectomy: transverse or vertical incision?" Revista da Associacao Medica Brasileira (1992) 67(3): 426‐430.
	OBJECTIVE: To determine if there is a difference between uterine incision techniques (vertical vs. transversal) in terms of clinical results. METHODS: All women with leiomyomas who underwent open abdominal myomectomy (n=61) between March and August 2016 at the Gynecology and Obstetrics Clinic at the Women's Health Research and Training Hospital Zekai Tahir Burak were included, and the clinical results were included and prospectively reviewed. RESULTS: The estimated blood loss during myomectomy increased in the transversal group compared with the vertical group (809.33�483.34 versus 405.32�180.95 mL, p<0.001). The average operation duration was 60 min, and the patients got discharged on the second day after surgery. No intergroup statistical differences were observed in the surgical procedure. CONCLUSIONS: Surgeons should give preference to the most viable incision depending on the size and location of the leiomyoma.

Vadala, M., et al. (2023). "Urethral Pain Syndrome: Treatment with Oxygen and Hyaluronic Acid." Open Access Macedonian Journal of Medical Sciences 11: 239-245.
	AIM: The aim of our clinical study has been to evaluate the efficacy of the association between high concentration oxygen and hyaluronic acid (HA) for the treatment of urethral pain syndrome (UPS). MATERIALS AND METHODS: Twenty women (45-65 years old) with suspected UPS diagnosis appealing to our Second Opinion Medical Consultation Network signed an informed consent form and were treated with oxygen/HA therapy treatment, 7 times a week, for a total of 5 weeks at the outpatient clinic (Clinic Ester Veronesi, Modena, Italy). The physicians of the Second Opinion Network followed up weekly from remote (WhatsApp, Skype) each treated patient as to state the effectiveness, tolerability, and side effects of the treatment. RESULT(S): We observed significant reductions in number of urgency urinary incontinence (-25.37 vs. -12.01 mean value), nocturia episodes (-24.01 vs. -11.23 mean value), volume voided in each micturition (-127.79 vs. -98.20 mean value), and micturitions per 24 h (-44.01 vs. -20.12 mean value). Analyses of the pre-and post-treatment scores showed a statistically significant improvement in Vaginal assessment scale, pain urgency frequency, and patient perception of bladder condition scale scores (p < 0.0305, p < 0.0001, and p < 0.0001, respectively). No side effects associated with the treatment were reported by the patients. CONCLUSION(S): We can highlight that Caressflow is effective and very well tolerated in UPS syndrome: The oxygen flow mixed with HA gives immediately a sense of freshness and urethro-bladder relaxation that lasts several hours. Further studies including larger sample sizes, placebo, and or challenge with other local and systemic treatments and different administration schedules versus longer follow-up are recommended.Copyright © 2023 Maria Vadala, Ester Veronesi, Flavio Garoia.

Vahdat, M., et al. (2022). "The effect of vitamin D on recurrence of uterine fibroids: A randomized, double-blind, placebo-controlled pilot study." Complementary Therapies in Clinical Practice 46: 101536.
	Background: and purpose: A deficiency of vitamin D has been suggested as one of the principal risk factors for uterine fibroids (UFs). We aimed to investigate the effect of vitamin D supplementation on the recurrence of UFs.; Materials and Methods: In a randomized, double-blind, placebo-controlled pilot study, women who had undergone hysteroscopic myomectomy from November 2017 to June 2020 were randomly given either vitamin D (1000 IU tablet; n = 55), or placebo (n = 54) daily for 12 months. Both groups were followed and compared in regard of the primary outcomes of the study, which were recurrence rates, size, and numbers of UFs based on three-dimensional transvaginal ultrasound investigation (3D-TVS). Data analysis was performed by the intention-to-treat (ITT) approach.; Results: The mean age of the study participants was 37.9 ± 6.5 years. The two groups did not differ significantly in terms of demographic and pre-intervention clinical characteristics. The administration of vitamin D supplements for one year reduced recurrence rates of UFs by 50% (p = 0.17). Vitamin D also reduced the size of recurrent UFs in the intervention group compared to controls (-7.7 mm), the difference was statistically different (p < 0.001). No adverse effect of vitamin D was reported in the present study.; Conclusion: Based on these results, vitamin D appears to be a promising and safe agent in the prevention of recurrence and reduction of the size of recurrent UFs, although further well-designed and appropriately powered studies are required to demonstrate a significant difference in the size and number of recurrent UFs. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Vahedian-Azimi, A., et al. (2021). "A systematic review and meta-analysis on the effects of statins on pregnancy outcomes." Atherosclerosis 336: 1-11.
	Background and Aims: Statins are contraindicated in pregnancy, due to their potential teratogenicity. However, data are still inconsistent and some even suggest a potential benefit of statin use against pregnancy complications. We aimed to investigate the effects of statins on pregnancy outcomes, including stillbirth, fetal abortion, and preterm delivery, through a systematic review of the literature and a meta-analysis of the available clinical studies.; Methods: A literature search was performed through PubMed, Scopus, and Web of Science up to 16 May 2020. Data were extracted from 18 clinical studies (7 cohort studies, 2 clinical trials, 3 case reports, and 6 case series). Random effect meta-analyses were conducted using the restricted maximum likelihood method. The common effect sizes were calculated as odds ratios (ORs) and their 95% confidence interval (CI) for each main outcome.; Results: Finally, nine studies were included in the meta-analysis. There was no significant association between statin therapy and stillbirth [OR (95% CI) = 1.30 (0.56, 3.02), p=0.54; I 2 = 0%]. While statin exposure was significantly associated with increased rates of spontaneous abortion [OR (95% CI) = 1.36 (1.10-1.68), p=0.004, I 2 = 0%], it was non-significantly associated with increased rates of induced abortion [OR (95% CI) = 2.08 (0.81, 5.36), p=0.129, I 2 = 17.33%] and elective abortion [OR (95% CI) = 1.37 (0.68, 2.76), p=0.378, I 2 = 62.46%]. A non-significant numerically reduced rate of preterm delivery was observed in statin users [OR (95% CI) = 0.47 (0.06, 3.70), p=0.47, I 2 = 76.35%].; Conclusions: Statin therapy seems to be safe as it was not associated with stillbirth or induced and elective abortion rates. Significant increase after statin therapy was, however, observed for spontaneous abortion. These results need to be confirmed and validated in future studies. (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Vaiarelli, A., et al. (2020). "The euploid blastocysts obtained after luteal phase stimulation show the same clinical, obstetric and perinatal outcomes as follicular phase stimulation-derived ones: a multicenter study." Human reproduction (Oxford, England) 35(11): 2598-2608.
	Study Question: Are the reproductive outcomes (clinical, obstetric and perinatal) different between follicular phase stimulation (FPS)- and luteal phase stimulation (LPS)-derived euploid blastocysts?; Summary Answer: No difference was observed between FPS- and LPS-derived euploid blastocysts after vitrified-warmed single embryo transfer (SET).; What Is Known Already: Technical improvements in IVF allow the implementation non-conventional controlled ovarian stimulation (COS) protocols for oncologic and poor prognosis patients. One of these protocols begins LPS 5 days after FPS is ended (DuoStim). Although, several studies have reported similar embryological outcomes (e.g. fertilization, blastulation, euploidy) between FPS- and LPS-derived cohort of oocytes, information on the reproductive (clinical, obstetric and perinatal) outcomes of LPS-derived blastocysts is limited to small and retrospective studies.; Study Design, Size, Duration: Multicenter study conducted between October 2015 and March 2019 including all vitrified-warmed euploid single blastocyst transfers after DuoStim. Only first transfers of good quality blastocysts (≥BB according to Gardner and Schoolcraft's classification) were included. If euploid blastocysts obtained after both FPS and LPS were available the embryo to transfer was chosen blindly. The primary outcome was the live birth rate (LBR) per vitrified-warmed single euploid blastocyst transfer in the two groups. To achieve 80% power (α = 0.05) to rule-out a 15% difference in the LBR, a total of 366 first transfers were required. Every other clinical, as well as obstetric and perinatal outcomes, were recorded.; Participants/materials, Setting, Methods: Throughout the study period, 827 patients concluded a DuoStim cycle and among them, 339 did not identify any transferable blastocyst, 145 had an euploid blastocyst after FPS, 186 after LPS and 157 after both FPS and LPS. Fifty transfers of poor quality euploid blastocysts were excluded and 49 patients did not undergo an embryo transfer during the study period. Thus, 389 patients had a vitrified-warmed SET of a good quality euploid blastocyst (182 after FPS and 207 after LPS). For 126 cases (32%) where both FPS- and LPS-derived good quality blastocysts were available, the embryo transferred was chosen blindly with a 'True Random Number Generator' function where '0' stood for FPS-derived euploid blastocysts and '1' for LPS-derived ones (n = 70 and 56, respectively) on the website random.org. All embryos were obtained with the same ovarian stimulation protocol in FPS and LPS (GnRH antagonist protocol with fixed dose of rec-FSH plus rec-LH and GnRH-agonist trigger), culture conditions (continuous culture in a humidified atmosphere with 37°C, 6% CO2 and 5% O2) and laboratory protocols (ICSI, trophectoderm biopsy in Day 5-7 without assisted hatching in Day 3, vitrification and comprehensive chromosome testing). The women whose embryos were included had similar age (FPS: 38.5 ± 3.1 and LPS: 38.5 ± 3.2 years), prevalence of male factor, antral follicle count, basal hormonal characteristics, main cause of infertility and previous reproductive history (i.e. previous live births, miscarriages and implantation failures) whether the embryo came from FPS or LPS. All transfers were conducted after warming in an artificial cycle. The blastocysts transferred after FPS and LPS were similar in terms of day of full-development and morphological quality.; Main Results and the Role of Chance: The positive pregnancy test rates for FPS- and LPS-derived euploid blastocysts were 57% and 62%, biochemical pregnancy loss rates were 10% and 8%, miscarriage rates were 15% and 14% and LBRs were 44% (n = 80/182, 95% CI 37-51%) and 49% (n = 102/207, 95% CI 42-56%; P = 0.3), respectively. The overall odds ratio for live birth (LPS vs FPS (reference)) adjusted for day of blastocyst development and quality, was 1.3, 95% CI 0.8-2.0, P = 0.2. Among patients with euploid blastocysts obtained following both FPS and LPS, the LBRs were also similar (53 (n = 37/70, 95% CI 41-65%) and 48% (n = 27/56, 95% CI 35-62%) respectively; P = 0.7). Gestational issues were experienced by 7.5% of pregnant women after FPS- and 10% of women following LPS-derived euploid single blastocyst transfer. Perinatal issues were reported in 5% and 0% of the FPS- and LPS-derived newborns, respectively. The gestational weeks and birthweight were similar in the two groups. A 5% pre-term delivery rate was reported in both groups. A low birthweight was registered in 2.5% and 5% of the newborns, while 4% and 7% showed high birthweight, in FPS- and LPS-derived euploid blastocyst, respectively. Encompassing the 81 FPS-derived newborns, a total of 9% were small and 11% large for gestational age. Among the 102 LPS-derived newborns, 8% were small and 6% large for gestational age. No significant difference was reported for all these comparisons.; Limitations, Reasons for Caution: The LPS-derived blastocysts were all obtained after FPS in a DuoStim protocol. Therefore, studies are required with LPS-only, late-FPS and random start approaches. The study is powered to assess differences in the LBR per embryo transfer, therefore obstetric and perinatal outcomes should be considered observational. Although prospective, the study was not registered.; Wider Implications of the Findings: This study represents a further backing of the safety of non-conventional COS protocols. Therefore, LPS after FPS (DuoStim protocol) is confirmed a feasible and efficient approach also from clinical, obstetric and perinatal perspectives, targeted at patients who need to reach the transfer of an euploid blastocyst in the shortest timeframe possible due to reasons such as cancer, advanced maternal age and/or reduced ovarian reserve and poor ovarian response.; Study Funding/competing Interest(s): None.; Trial Registration Number: N/A. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Valadon, C., et al. (2023). "Treatment of Female Stress Urinary Incontinence with Urethral Bulking." Current Bladder Dysfunction Reports 18(2): 118-123.
	Purpose of Review: To review the current use of urethral bulking agents (UBAs) for the treatment of female stress urinary incontinence (SUI). Recent Findings: The newest FDA-approved agent, Bulkamid (2022), which has demonstrated > 60% rate of improvement at 7 years. A systematic review published in 2021 showed similar long-term success rates between Bulkamid (42-70%), Coaptite (60-75%), and Macroplastique (21-80%). To date, direct comparisons of UBAs have not been published. Bulkamid may have a more favorable side effect profiles with no cases of erosion or migration reported. Summary: Multiple UBAs are available on the market have demonstrated similar improvements in SUI with minimal adverse events. Choice of UBA should be based on surgeon comfort with technique, as each has a unique injection technique, and consideration for potential side effects depending on the material of the agent.Copyright © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Valedi, S., et al. (2022). "The efficacy of eye movement desensitization and reprocessing in reducing anxiety among female university students with primary dysmenorrhea." BMC Psychology 10(1): 50.
	Background: Unpleasant experiences of dysmenorrhea can lead to increased anxiety. The anxiety associated with dysmenorrhea is a pain-related anxiety which might reduce the efficacy of medication as well as enhance the perception of pain. The present study evaluated the efficacy of eye movement desensitization and reprocessing (EMDR) in reducing anxiety among female university students with primary dysmenorrhea.; Methods: In this randomized controlled trial, 88 female university students were recruited from April 2019 to February 2020. Eligible participants were selected by convenience sampling and were allocated into study groups (44 individuals in the intervention group and comparison group) using balanced block randomization. The final sample comprised 78 participants who completed the study (39 individuals in each group). Data were collected using the Spielberger State-Trait Anxiety Inventory, Subjective Units of Distress Scale, and Validity of Cognition Scale before the intervention and at the time of the first menstrual period after completion of the intervention. The intervention group received EMDR in two individual interventional sessions which lasted approximately one hour. Data analysis was performed using analysis of variance with control of covariance method at a significance level of 0.05.; Results: The results of the study showed that EMDR did not have a statistically significant effect on State-Trait Anxiety of patients with dysmenorrhea (p > 0.05). Based on the Cohen's d effect size of 0.06 for state-anxiety, -0.01 for trait-anxiety, and partial eta square less than 0.059 for both uncorrected and corrected models, the intervention was within a trivial effect.; Conclusion: EMDR intervention did not have a statistically and clinically significant effect on State-Trait Anxiety of patients with dysmenorrhea. Therefore, the efficacy of EMDR in treating dysmenorrhea-related anxiety remains inconclusive. Trial registration IRCT20180823040851N2 on 2019-02-09. (© 2022. The Author(s).)

Valencia University, o. (2021). Effectiveness of a Manual Therapy Protocol on Women With Pelvic Pain Due to Endometriosis.
	No Results Available Other: Manual therapy|Other: Placebo treatment Endometriosis symptoms. The endometriosis health profile questionnaire (EHP-30Q)|Health related quality of life. 36-Item Short Form Survey (SF-36)|Lumbar range of movement. Modified Schober Test|Depression. Beck Depression Index (BDI-II)|Anxiety. State Trait Anxiety Index (STAI)|Medication intake. Diary|Impression of change after treatment. Patient global Perception of Change Scale (PGICS) Female Not Applicable 40 Other Allocation: Randomized|Intervention Model: Factorial Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Treatment 19866206 March 30, 2023

Valentin, N., et al. (2021). "Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis." The American journal of gastroenterology 116(3): 491-504.
	Introduction: Liver transplantation (LT) remains the gold standard for treatment of end-stage liver disease. Given the increasing number of liver transplantation in females of reproductive age, our aim was to conduct a systematic review and meta-analysis evaluating pregnancy outcomes after LT.; Methods: MEDLINE, Embase, and Scopus databases were searched for relevant studies. Study selection, quality assessment, and data extraction were conducted independently by 2 reviewers. Estimates of pregnancy-related outcomes in LT recipients were generated and pooled across studies using the random-effects model.; Results: A comprehensive search identified 1,430 potential studies. Thirty-eight studies with 1,131 pregnancies among 838 LT recipients were included in the analysis. Mean maternal age at pregnancy was 27.8 years, with a mean interval from LT to pregnancy of 59.7 months. The live birth rate was 80.4%, with a mean gestational age of 36.5 weeks. The rate of miscarriages (16.7%) was similar to the general population (10%-20%). The rates of preterm birth, preeclampsia, and cesarean delivery (32.1%, 12.5%, and 42.2%, respectively) among LT recipients were all higher than the rates for the general US population (9.9%, 4%, and 32%, respectively). Most analyses were associated with substantial heterogeneity.; Discussion: Pregnancy outcomes after LT are favorable, but the risk of maternal and fetal complications is increased. Large studies along with consistent reporting to national registries are necessary for appropriate patient counseling and to guide clinical management of LT recipients during pregnancy. (Copyright © 2021 by The American College of Gastroenterology.)

Valiton, V., et al. (2019). "Obstetrical and postpartum complications in women with hereditary fibrinogen disorders: A systematic literature review." Haemophilia : the official journal of the World Federation of Hemophilia 25(5): 747-754.
	Introduction: Hereditary fibrinogen disorders (HFD) are rare quantitative or qualitative fibrinogen anomalies, including afibrinogenaemia (A), hypofibrinogenaemia (H), dysfibrinogenaemia (D) and hypodysfibrinogenaemia (HD). As fibrinogen plays an essential role in pregnancy, we addressed the issue of obstetrical and postpartum complications in women with HFD.; Methods: A systematic literature review, restricted to English manuscripts, was conducted according to the PRISMA guidelines. We searched through the MEDLINE database for English articles, published from January 1985 until November 2018, focusing on pregnancy in A, H, D and HD. A total of 198 articles were identified, 15 articles were added from other sources. Overall, 213 articles were screened and 54 were included in the final analysis.; Results: A total of 188 pregnancies from 70 women were analysed. About half of pregnancies resulted in miscarriage; more specifically in 15 (42.9%), 36 (46.8%), 27 (42.9%) and 4 (30.8%) of A, H, D and HD patients, respectively. Preterm complications were also frequent (33.5%). Metrorrhagia, mainly in the first trimester, was observed in 21.7% of the pregnancies. Placenta abruption was reported in 5 (14.3%), 4 (5.2%), 5 (7.9%) and 1 (7.7%) of A, H, D and HD, respectively. A total of 24 (12.7%) deliveries were complicated by postpartum thrombotic events (3.2%) or postpartum haemorrhage (9.6%). A fibrinogen replacement therapy was introduced in 30% of pregnancies, as prophylaxis (81.1%) or on demand (18.9%).; Conclusion: These results suggest that women with HFD are at high risk of obstetrical and postpartum complications. Prospective international registries may allow to identify more precisely the incidence of obstetrical and postpartum adverse outcomes and their management. (© 2019 John Wiley & Sons Ltd.)

Valladolid University, o. (2022). Therapeutic Exercise and Education in Neurophysiology of Pain in the Quality of Life of Women With Endometriosis.
	No Results Available Other: Physiotherapy|Other: Sham, Control Changes in quality of life perception assessed using EUROQuOL 5D - 5L|Abdominal wall muscle thickness|Sexual Function assessed usinf Female Sexual Function Index (IFSF)|Symptoms associated with menstruation assessed using CVM-22 (quality of life related to menstruation) Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Treatment EndometriosisCdV2022 January 12, 2024

Valladolid University, o. (2022). Therapeutic Exercise and Education in Pain Neurophysiology to Improve Pain Intensity in Women With Endometriosis. Clinical Trial.
	No Results Available Other: Therapeutic exercise AND pain neurophysiology education|Other: Sham Changes in pain perception assessed using a 100mm Visual Analogue Scale (VAS)|Changes in Kinesiofobia assessed using the Tampa Scale of Kinesiofobia (TSK)|Changes in Catastrophism assesed using the Pain Catastrophism Scale (PCS)|Impression of the overall improvement obtained with the treatment ussing the Global rating of changes scale (GROC) Female Not Applicable 60 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Treatment Endometriosis2022 January 12, 2024

van de Laar, R. L. O., et al. (2020). "Adjuvant VACcination against HPV in surgical treatment of Cervical Intra-epithelial Neoplasia (VACCIN study) a study protocol for a randomised controlled trial." BMC Cancer 20(1): 539.
	Background: Cervical cancer is caused by Human Papilloma viruses (HPV) and is preceded by precursor stages: Cervical Intraepithelial Neoplasia (CIN). CIN is mostly found in women in their reproductive age and treated with a Loop Electrosurgical Excision Procedure (LEEP). The recurrence or residual disease rate after treatment is up to 17%. These women have a lifelong increased risk of recurrent CIN, cervical cancer and other HPV related malignancies. Furthermore, LEEP treatments are associated with complications such as premature birth. Limited data show that prophylactic HPV vaccination at the time of LEEP reduces recurrence rates, therefore leading to a reduction in repeated surgical interventions and side effect like preterm birth. The primary study objective is to evaluate the efficacy of the nonavalent HPV vaccination in women with a CIN II-III (high-grade squamous intraepithelial lesion (HSIL) lesion who will undergo a LEEP in preventing recurrent CIN II-III after 24 months.; Methods: This study is a randomised, double blinded, placebo controlled trial in 750 patients without prior HPV vaccination or prior treatment for CIN and with histologically proven CIN II-III (independent of their hrHPV status) for whom a LEEP is planned. Included patients will be randomised to receive either three injections with nonavalent (9 HPV types) HPV vaccine or placebo injections (NaCL 0.9%) as a comparator. Treatment and follow-up will be according the current Dutch guidelines. Primary outcome is recurrence of a CIN II or CIN III lesion at 24 months. A normal PAP smear with negative hrHPV test serves as surrogate for absence of CIN. At the start and throughout the study HPV typing, quality of life and cost effectiveness will be tested.; Discussion: Although prophylactic HPV vaccines are highly effective, little is known about the effectivity of HPV vaccines on women with CIN. Multiple LEEP treatments are associated with complications. We would like to evaluate the efficacy of HPV vaccination in addition to LEEP treatment to prevent residual or recurrent cervical dysplasia and decrease risks of repeated surgical treatment.; Trial Registration: Medical Ethical Committee approval number: NL66775.078.18. Affiliation: Erasmus Medical Centre. Dutch trial register: NL 7938. Date of registration 2019-08-05.

van den Beukel, B. A. W., et al. (2022). "Analgesia in patients with adhesion-related chronic abdominal and pelvic pain after surgery: a systematic review." Acta chirurgica Belgica 122(5): 303-311.
	Background and Objective: Adhesions are the most common cause of chronic abdominal pain after surgery. Surgical adhesiolysis can relieve symptoms in selected patients, but many require other treatments. The aim of this study is to evaluate analgesic treatments other than abdominal surgery in chronic pain related to adhesions.; Database and Data Treatment: A search was conducted in PubMed, Embase, and Central. Studies with patients suffering from chronic postoperative pain related to adhesions and undergoing all types' analgesic treatment were included. The primary outcome was the number of patients who improved in pain at long-term follow-up (at least 1 year). Secondary outcomes included improvement in pain at 3 months follow-up, quality of life, and physical functioning.; Results: Searches identified 3022 citations. Four studies were included, one trial, one cohort study, and two case reports. The primary outcome was not reported. In a small trial ( n = 18) pregabalin tended to have a benefit over placebo improving pain at 3 months. In the cohort study, 17 patients with chronic pelvic pain underwent a trial of sacral nerve stimulation. Eight patients who responded positively received an implanted device for continuous modulation, reporting sustainable improvement during follow-up (range: 6-36 months). One case report described improved pain at 6 months with trans-abdominis plane stimulation. The second report described improvement of physical function with manual therapy at long-term follow-up.; Conclusions: Low level of evidence is available regarding analgesic treatments of chronic abdominal and pelvic pain related to adhesions. The benefit of pregabalin is doubtful; nerve modulation is promising in a selected group.HighlightsAdhesions are a frequent cause of chronic abdominal and pelvic pain after surgery.Many patients are not good candidates for surgery (Adhesiolysis) or have relapses of pain.There is an important knowledge gap regarding non-surgical analgesic treatment.Analgesia in adhesion-related chronic abdominal pain after surgery.

van den Heerik, A., et al. (2023). "Early toxicity and quality of life after molecular-based adjuvant treatment in the PORTEC-4a trial." Radiotherapy and Oncology 182(Supplement 1): S483-S484.
	Purpose or Objective The international PORTEC-4a trial was the first trial to incorporate molecular factors in decision making on adjuvant treatment for women with early stage high-intermediate risk endometrial cancer (HIR-EC). For patients allocated to the intervention arm, adjuvant treatment was based upon a molecular-integrated risk profile. The present analyses were performed to compare health-related quality of life (HRQL) and adverse event (AE) rates between the treatment arms in the first 6 months after randomisation. Materials and Methods Patients with HIR-EC were randomised (2:1) between individualised treatment based upon a molecular-integrated risk profile or standard vaginal brachytherapy (VBT). In case of a favourable profile, adjuvant treatment was omitted. Those with an intermediate profile received VBT while those with an unfavourable risk profile received pelvic radiotherapy (EBRT). HRQL was assessed with the EORTC-QLQ C30 and EN24 module at baseline, after treatment and 6 monthly after randomisation. AE were graded using the CTCAE v4.0. Analyses were performed on the per-protocol population. Prevalence of toxicity was calculated at each timepoint and compared using Fisher's exact test. Analysis of HRQL was done according to the EORTC guidelines. Symptoms rated as "quite a bit" or "very much" were considered 'severe'. A 2-sided p<0.01 was considered statistically significant, and p<0.05 reported as a trend. Results Between 2012 and 2021, 563 evaluable patients were included, 367 in the molecular arm vs 196 in the standard arm, see figure 1. In 46.7% of patients in the molecular arm adjuvant treatment was omitted. Grade >=2 AE were reported in 59 patients at completion of treatment: 41 (11.4%) in the interventional arm vs 18 (8.9%) in the standard arm (p=0.39); at 6 months, this was 44 (12.2%) vs 22 (10.9%), p=0.36. Grade 3 AE were reported for 4 patients (3 in the molecular arm and 1 in the standard arm) at treatment completion, and for 8 (4 vs 4) at 6 months. There were no grade 4 or 5 AE. During treatment all grade 3 AE were genitourinary or vaginal, whereas at 6 months only 1 was related to treatment. 94.7% completed HRQL assessment at baseline, 81.0% during treatment and 82.2% at 6 months. No significant differences between the two arms were found for physical functioning (p=0.31) and global health status (p=0.10). Social and role functioning improved over time in both arms (p<0.001). A trend for better role functioning over time was seen for patients treated according to their molecular profile compared to standard VBT (p=0.014). Conclusion Use of adjuvant treatment was greatly reduced by individualised treatment in the molecular arm of the PORTEC-4a trial. In the first 6 months no significant difference in early toxicity and HRQL were found between molecular-based adjuvant treatment and standard brachytherapy, while a strong trend for better role functioning after individualised treatment was observed. [Figure presented]Copyright © 2023 Elsevier B.V.

van den Heerik, A., et al. (2023). "Early toxicity and quality of life after molecular-based adjuvant treatment in the PORTEC-4a trial."  182: S483‐S484.
	Purpose or Objective The international PORTEC‐4a trial was the first trial to incorporate molecular factors in decision making on adjuvant treatment for women with early stage high‐intermediate risk endometrial cancer (HIR‐EC). For patients allocated to the intervention arm, adjuvant treatment was based upon a molecular‐integrated risk profile. The present analyses were performed to compare health‐related quality of life (HRQL) and adverse event (AE) rates between the treatment arms in the first 6 months after randomisation. Materials and Methods Patients with HIR‐EC were randomised (2:1) between individualised treatment based upon a molecular‐integrated risk profile or standard vaginal brachytherapy (VBT). In case of a favourable profile, adjuvant treatment was omitted. Those with an intermediate profile received VBT while those with an unfavourable risk profile received pelvic radiotherapy (EBRT). HRQL was assessed with the EORTC‐QLQ C30 and EN24 module at baseline, after treatment and 6 monthly after randomisation. AE were graded using the CTCAE v4.0. Analyses were performed on the per‐protocol population. Prevalence of toxicity was calculated at each timepoint and compared using Fisher's exact test. Analysis of HRQL was done according to the EORTC guidelines. Symptoms rated as “quite a bit” or “very much” were considered ‘severe’. A 2‐sided p<0.01 was considered statistically significant, and p<0.05 reported as a trend. Results Between 2012 and 2021, 563 evaluable patients were included, 367 in the molecular arm vs 196 in the standard arm, see figure 1. In 46.7% of patients in the molecular arm adjuvant treatment was omitted. Grade ≥2 AE were reported in 59 patients at completion of treatment: 41 (11.4%) in the interventional arm vs 18 (8.9%) in the standard arm (p=0.39); at 6 months, this was 44 (12.2%) vs 22 (10.9%), p=0.36. Grade 3 AE were reported for 4 patients (3 in the molecular arm and 1 in the standard arm) at treatment completion, and for 8 (4 vs 4) at 6 months. There were no grade 4 or 5 AE. During treatment all grade 3 AE were genitourinary or vaginal, whereas at 6 months only 1 was related to treatment. 94.7% completed HRQL assessment at baseline, 81.0% during treatment and 82.2% at 6 months. No significant differences between the two arms were found for physical functioning (p=0.31) and global health status (p=0.10). Social and role functioning improved over time in both arms (p<0.001). A trend for better role functioning over time was seen for patients treated according to their molecular profile compared to standard VBT (p=0.014). Conclusion Use of adjuvant treatment was greatly reduced by individualised treatment in the molecular arm of the PORTEC‐4a trial. In the first 6 months no significant difference in early toxicity and HRQL were found between molecular‐based adjuvant treatment and standard brachytherapy, while a strong trend for better role functioning after individualised treatment was observed. [Figure presented]

Van Der Arend, B. W., et al. (2022). "Hormonal treatment for menstrual migraine: Rationale and protocol of the WHAT!-Trial." Cephalalgia 42(1 Supplement): 62.
	Introduction: Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggested a beneficial effect of hormonal contraceptives, but no large randomized controlled trial has been performed. In clinical practice combined oral contraceptive pills are often prescribed for migraine in women. As proof of efficacy is lacking and usage may be accompanied by side effects, with even an increased relative risk for stroke in young women with migraine with aura, there is a great need for research on this topic. In a small study a beneficial effect of vitamin E with respect to pain severity and functional disability was described.1 Its effect was suggested to be mediated by a reduction of prostaglandin production in the endometrium. Objective(s): To study the efficacy of continuous daily use of ethinylestradiol/levonorgestrel (30/150 mug/day) compared to vitamin E (400 IU/day) in the treatment of menstrual migraine. Method(s): Women with menstrual migraine (n=180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150mug or vitamin E 400IU. The study is an open-label study since we consider it practically and ethically not feasible to blind participants for the use of oral contraceptives. Vitamin E is chosen as an active comparator. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, participants fill out our headache E-Diary, in which they provide daily information about presence of headache, its characteristics and accompanying symptoms, aura symptoms, use of acute (pain) medication and menstrual bleeding.2-4 Our time-locked E-diary includes an automated algorithm differentiating headache and migraine days based on ICHD-3 criteria.5 Since patient's expectancy may greatly influence treatment response in open-label studies, the Stanford Expectations of Treatment Scale (SETS) will be used to help assess expectancy effects of both interventions. Result(s): Primary outcome will be change in monthly migraine days (MMD) from baseline (week -4 to 0) to the last 4 weeks of treatment (weeks 9-12). Secondary outcomes will be change in monthly headache days (MHD), and 50% responder rates of MMD and MHD. Conclusion(s): The WHAT!-Trial aims to investigate superiority of continuous oral contraceptive treatment for menstrual migraine. Results may be implemented in clinical practice at short notice.

van der Arend, B. W. H., et al. (2024). "Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!)." Trials 25(1): 123.
	Background: Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic. Method(s): Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 mug or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days. Result(s): The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks - 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD. Conclusion(s): The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible. Trial registration: Clinical trials.gov NCT04007874. Registered 28 June 2019.Copyright © The Author(s) 2024.

Van Der Ham, K., et al. (2022). "Pregnancy Rate and Outcomes Following a Randomized Controlled Three-component Lifestyle Intervention in Women with PCOS." Journal of the Endocrine Society 6(Supplement 1): A686.
	PCOS (polycystic ovary syndrome) is associated with overweight and obesity. Women with PCOS and overweight or obesity present with more pronounced reproductive derangements. Moreover, when pregnant, pregnancy complications such as gestational diabetes, hypertensive disorders and preterm birth seem to be more prevalent in this population. The present study is a one-year randomized controlled trial to investigate the effect of a three-component (cognitive behavioral therapy, healthy diet and physical therapy) lifestyle intervention (LSI) with or without Short Message Service (SMS) on pregnancy leading to live birth, pregnancy complications and outcomes within 24 months after the start of the lifestyle intervention compared to care as usual (CAU). We hypothesized that prepregnancy weight loss and the adoption of a healthy lifestyle would cause more pregnancies, shorter time to conception and less pregnancy complications. Women diagnosed with PCOS according to the Rotterdam 2003 criteria and a BMI above 25 kg/m2 were included. A total of 183 participants were randomly assigned to three groups: 1) threecomponent lifestyle intervention with SMS (LSI SMS+); 2) three-component lifestyle intervention without SMS (LSI SMS-); 3) care as usual (CAU): encourage to lose weight autonomously (control group). Pregnancy and neonatal outcomes were collected from the Dutch Bureau of Statistics (CBS) combined with the Dutch Perinatal registry (Perined). Within 24 months after the start of the intervention the pregnancy rate leading to live birth was 41.7% (25/60) within SMS+, 38.1% (24/63) within SMS- and 38.3% (23/60) within CAU. This was non-significant between the groups. Mean time to pregnancy for SMS+ was 18.3 months, 19.1 months for SMS- and 19.4 months for CAU (p=0.775). Gestational diabetes (LSI: 8.2% vs CAU: 21.7%, p=0.133), hypertensive disorders (LSI: 8.2% vs CAU: 13.0%, p=0.673) and preterm birth (LSI: 12.2% vs CAU: 17.4%, p=0.716) rates were all lower in the LSI groups (SMS+ and SMS- combined) compared to CAU. This trial demonstrated a non-significant positive trend in pregnancy outcomes in favor of the lifestyle intervention groups. We believe that a pre-pregnancy three-component lifestyle intervention in overweight or obese women with PCOS supports the attempts to get a healthy pregnancy by creating weight loss with positive effects on their physical and mental health.

Van der Heijden Beatrice, I. J. M., et al. (2021). "Menopause and Sustainable Career Outcomes: A Science Mapping Approach." International Journal of Environmental Research and Public Health 18(23).
	This paper provides a systematic review of the phenomenon of menopause at the workplace from a sustainable career perspective, by highlighting its major themes along with the evolution and tendencies observed in this field. A conceptual science mapping analysis based on co-word bibliographic networks was developed, using the SciMAT tool. From 1992 to 2020, 185 documents were retrieved from the Web of Science. In the first analyzed time span (1992-2002), postmenopausal women , health , and risk factors appeared to be the motor themes (well-developed and important for the structure of the discipline under focus), and disorder was an emerging or disappearing theme in the phenomenon under research. In the second studied period (2003-2013), risk and health were motor themes, menopausal symptoms was a basic or transversal theme (important for the discipline but not well-developed), coronary heart disease was a specialized theme (well-developed but less important for the structure of the research field), and postmenopausal women was an emerging or disappearing theme (both weakly developed and marginal to the field). In the third studied period (2014-2020), menopause , breast cancer , and menopausal symptoms were motor themes, Anxiety was a specialized theme and risk and body mass index were emerging or disappearing themes. Sustainability of women's careers in the second half of life is of increasing importance given the increasing equal representation of men and women in working organizations, and the impact of the changing nature of work in the 21st century on older workers.

van der Horst, R. L., et al. (2022). "The role of multimodal adjuvant therapy for FIGO I-II carcinosarcoma of the uterus: a systematic review." Critical Reviews in Oncology/Hematology 175: 103701.
	The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

van der Houwen, L. E. E., et al. (2019). "Continuous oral contraceptives versus long-term pituitary desensitization prior to IVF/ICSI in moderate to severe endometriosis: study protocol of a non-inferiority randomized controlled trial." Human Reproduction Open 2019(1): hoz001.
	Study Questions: The primary objective is to investigate if continuous use of oral contraceptives is non-inferior compared to long-term pituitary desensitization with a GnRH agonist prior to IVF/ICSI in patients with moderate to severe endometriosis with regard to treatment efficacy. Secondary objectives concern treatment safety and cost-effectiveness.; What Is Known Already: Long-term pituitary desensitization with a GnRH agonist for 3-6 months prior to IVF/ICSI improves clinical pregnancy rates in women suffering from endometriosis. However, discussion about this treatment strategy exists because of its uncomfortable side effects. Alternatively, IVF/ICSI pre-treatment with continuously administered oral contraceptives may offer fewer side-effects and lower (in)direct costs, as well as encouraging IVF outcomes in women with endometriosis. To date, these two different IVF/ICSI pre-treatment strategies in women with endometriosis have not been directly compared.; Study Design Size Duration: An open-label, parallel two-arm randomized controlled multicenter trial is planned, including patients with moderate to severe endometriosis. To demonstrate an absolute difference of 13% (delta of 10% with non-inferiority margin of 3%) with a power of 80% 137 patients per group are sufficient. Taking into account a withdrawal of patients of 10% and a cancelation rate of embryo transfer after ovarian pick up of 10% (for instance due to fertilization failure), the sample size calculation is rounded off to 165 patients per group; 330 patients in total will be included. After informed consent, eligible patients will be randomly allocated to the intervention or reference group by using web based block randomization stratified per centre. Study inclusion is expected to be complete in 3-5 years.; Participants/materials Setting Methods: The research population consists of patients with moderate to severe endometriosis (ASRM III/IV) who are scheduled for their first, second or third IVF/ICSI treatment attempt. Women aged over 41 years, younger than 18 years, with a known contraindication for the use of oral contraceptives and/or GnRH agonists or with severe male factor infertility will be excluded from participation. After informed consent patients are allocated to the intervention group (one-phase oral contraceptive continuously during three subsequent months) or the reference group (three Leuprorelin 3.75 mg i.m./s.c. depot injections during three subsequent months). Tibolon 2.5 mg can be given daily as add-back therapy in the reference group. After 3 months of pre-treatment the IVF/ICSI stimulation phase will be started. The primary outcome is live birth rate after fresh embryo transfer. Secondary outcomes are cumulative live birth rate after one IVF/ICSI treatment cycle (including fresh and frozen embryo transfers up to 15 months after randomization), ongoing pregnancy rate and time to pregnancy. In addition, treatment outcome parameters, adverse events, side-effects during the first 3 months, complications, recurrence of endometriosis (complaints), quality of life, patient preferences, safety and costs effectiveness will be reported. Measurements will be performed at baseline and at 3, 6, 9, 12 and 15 months after randomization.; Study Funding/competing Interests: All authors have no conflict of interest related to this manuscript. The department of reproductive medicine of the Amsterdam UMC location VUmc has received several research and educational grants from Guerbet, Merck and Ferring not related to the submitted work.; Trial Registration Number: The trial is registered as the COPIE trial (Continuous use of Oral contraceptives as an alternative for long-term Pituitary desensitization with a GnRH agonist prior to IVF/ICSI in Endometriosis patients) in the Dutch Trial Register (Ref. No. NTR6357, http://www.trialregister.nl).; Trial Registration Date: 16 March 2017.; Date of First Patient’s Enrolment: Enrollment is planned for November 2018.

van der Kooi Anne-Lotte, L. F., et al. (2019). "Perinatal complications in female survivors of cancer: a systematic review and meta-analysis." European journal of cancer (Oxford, England : 1990) 111: 126-137.
	Background: Observational studies have suggested that perinatal outcomes are worse in offspring of cancer survivors. We conducted a systematic review and meta-analysis to examine the risks of perinatal complications in female cancer survivors diagnosed before the age of 40 years.; Methods: All published articles on pregnancy, perinatal or congenital risks in female cancer survivors were screened for eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.; Results: Twenty-two studies met the inclusion criteria. Meta-analysis indicates that offspring of cancer survivors are at increased risk of prematurity (relative risk [RR]: 1.56; 95% confidence interval [CI] 1.37-1.77) and low birth weight (RR 1.47; 95% CI 1.24-1.73) but not of being small for gestational age (RR 0.99; 95% CI 0.81-1.22). Cancer survivors have higher rates of elective (RR: 1.38; 95% CI 1.13-1.70) and emergency caesarean section (RR: 1.22; 95% CI 1.15-1.30) as well as assisted vaginal delivery (RR: 1.10; 95% CI 1.02-1.18) and are at increased risk of postpartum haemorrhage (RR: 1.18; 95% CI 1.02-1.36). The risk of congenital abnormalities also appears increased (RR 1.10; 95% CI 1.02-1.20), but this is likely to be an artefact of analysis. Although meta-analysis of the effects of radiotherapy was not possible for all outcomes, there was an increased risk of prematurity (RR 2.27; 95% CI 1.34-3.82) and consistent findings of low birth weight (RR 1.38-2.31). Risk of being small for gestational age was increased only after high uterine radiotherapy dosage.; Conclusion: The increased perinatal risks warrant a proactive approach from healthcare providers in both counselling and management of perinatal care for cancer survivors. (Copyright © 2019. Published by Elsevier Ltd.)

van der Ploeg, P., et al. (2021). "The effectiveness of monotherapy with PI3K/AKT/mTOR pathway inhibitors in ovarian cancer: A meta-analysis." Gynecologic Oncology 163(2): 433-444.
	Objective: To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/mTOR biomarkers on therapy response.; Methods: A systematic search was conducted in PubMed, Embase and the Cochrane Library for articles reporting on treatment with PI3K/AKT/mTOR inhibitors in ovarian cancer. The primary endpoint was defined as the clinical benefit rate (CBR), including the proportion of patients with complete (CR) and partial response (PR) and stable disease (SD). Secondary endpoints included the overall response rate (ORR, including CR and PR) and drug-related grade 3 and 4 adverse events.; Results: We included 233 patients from 19 studies and observed a pooled CBR of 32% (95% CI 20-44%) and ORR of 3% (95% CI 0-6%) in advanced or recurrent ovarian cancer patients treated with PI3K/AKT/mTOR inhibitors. Subgroup analysis tended to favor the studies who selected patients based on current PI3K/AKT/mTOR biomarker criteria (e.g. genomic alterations or loss of PTEN protein expression), but the difference in CBR was not statistically significant from studies with unselected populations (respectively, CBR of 42% (95% CI 23-62%) and 27% (95% CI 14-42%), P = 0.217). To better reflect true patient benefit, we excluded SD <6 months as a beneficial outcome which resulted in a pooled CBR of 7% (95% CI 2-13%). The overall proportion of patients with drug-related grade 3 and 4 adverse events was 36%.; Conclusions: The efficacy of monotherapy with PI3K/AKT/mTOR inhibitors in advanced recurrent ovarian cancer patients is limited to a small subgroup and selection of patients with the use of current biomarkers did not improved the CBR significantly. Given the toxicity profile, we suggest that current treatment with PI3K/AKT/mTOR inhibitors should not be initiated unless in clinical trials. Furthermore, improved biomarkers to measure functional PI3K/AKT/mTOR pathway activity are needed to optimize patient selection.; Competing Interests: Declaration of Competing Interest PvdP is employed by Catharina Hospital, where her research work is co-funded by the Catharina research fund, and Molecular Pathway Dx, Philips. AvdS is employed by Molecular Pathway Dx, Philips. The other authors declare no conflict of interest. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Van der Riet, P., et al. (2020). "Exploring the impacts of mindfulness and yoga upon childbirth outcomes and maternal health: an integrative review." Scandinavian journal of caring sciences 34(3): 552-565.
	BACKGROUND: Foetal development and the long-term outcomes of the infant are influenced by the intrauterine environment. Strategies to enhance maternal health in pregnancy are needed to improve health outcomes for childbearing women and babies, advancing the well-being of our general population. AIM: To synthesise the existing literature to determine the impacts of mindfulness and yoga practice upon birth outcomes and maternal health. METHODS: An integrative literature review using Whittemore and Knafl's framework was undertaken in 2016-2017. Two search strategies included database peer-reviewed journal articles and ancestry searching, that is exploring the reference list of relevant research articles. After screening and checking the eligibility, a total of 12 articles were included in this review. Data analysis involved coding, visual displays, thematic analysis and comparison, and conclusion drawing. RESULTS: The results of this review identified a broad theme that mindfulness and yoga practice is associated with improved maternal mental health antenatally and postnatally. Subthemes have been presented under the central theme including the following: increased mindfulness correlates with decreased fear of childbirth; reduced symptoms of anxiety and depression; and supportive group settings found to be beneficial by pregnant women. CONCLUSION: The evidence presented in this review suggests that mindfulness and yoga practice are feasible and cost-effective interventions to enhance maternal mental health, particularly for women experiencing mental health challenges. Mindfulness and yoga practised regularly in the antenatal period can significantly promote the health of pregnant women and potentially their developing babies.

Van Der Vaart, L., et al. (2022). "Pessary or Surgery for a Symptomatic Pelvic Organ Prolapse; a Multicenter Randomized Controlled Trial." International Urogynecology Journal 33(Supplement 2): S182-S183.
	Introduction: Pelvic organ prolapse (POP) can negatively affect the quality of life. Due to ageing, the number of women presenting with symptomatic POP will increase dramatically. Treatment options for moderate to severe POP are pessary and surgery. Currently, treatment selection is based on patients and physicians preference. Studies comparing pessary and surgery in a randomized setting are lacking. Therefore, we performed this multicenter randomized controlled trial (RCT) comparing both treatment modalities. Objective(s): To present the 1-year interim results of a 2-year RCT comparing the efficacy of pessary and surgery for women presenting with symptomatic POP. Method(s): Multicenter RCT to prove non-inferiority of pessary as compared to surgery, including women with symptomatic POP stage >= 2 and a successful pessary fitting procedure. The primary outcome was subjective improvement at 12-months follow-up, defined as responding 'very much' or 'much improvement' to the Patient Global Impression of Improvement (PGI-I) questionnaire. Secondary outcomes included symptom bother measured with the Pelvic Floor Distress Inventory (PFDI-20), adverse events and cross-over of therapy. In the PFDI-20, a higher score represents more bothersome symptoms. With 198 women per group, we would achieve 80% power to reject the null hypothesis that pessary therapy is inferior to surgery, with a 1-sided alpha of 0.05 and a non-inferiority margin of 10%. Analysis of the primary outcome was done using the Manning-Farrington test for non-inferiority for the difference between two proportions, against the non-inferiority margin of 10% risk difference. Continuous data were analysed using the independent t-test, with 95% confidence intervals (CI) estimated using bootstrapping. Result(s): A total of 439 women were included, 218 (49.7%) women in the pessary group and 221 (50.3%) women in the surgery group. A total of 96 (44.0%) women in the pessary group switched to surgery and in the surgery group re-surgery was performed in 7 (3.2%) women and 2 (0.9%) women additionally used a pessary. In the intention-to-treat analysis, subjective improvement was reported by 75.9% of women in the pessary group and 82.3% in the surgery group (risk difference 6.3%; 90% CI -13.3% - 0.6%; p-value for non-inferiority 0.20). Both groups showed an improvement on all subscales scores of the PFDI- 20, without significant difference between groups. In a per-protocol analysis, subjective improvement was reported by 67.3% of women in the pessary group and 84.8% of women in the surgery group (risk difference 17.5%; 90% CI -26.1% - -8.8%; p-value for non-inferiority 0.92). Additionally, the per-protocol analysis showed that significantly more women in the surgery group gained a significantly greater reduction on the UDI-6 scale (mean difference 5.6; 95% CI 0.4 - 10.6; p-value 0.02) and on the total PFDI-20 scale (mean difference 11.3; 95%CI 1.0 - 21.4; p-value 0.03), as compared to the pessary group. Conclusion(s): For women presenting with symptomatic POP, surgery, as compared with initial pessary, results in higher rates of subjective improvement at 1-year. Moreover, over 40% of women initially treated with a pessary was indicated for surgery within the first year. Our data showed that surgery should be considered as primary intervention for symptomatic POP.

Van Der Vaart, L., et al. (2022). "PESSARY OR SURGERY FOR A SYMPTOMATIC PELVIC ORGAN PROLAPSE; A MULTICENTER RANDOMIZED CONTROLLED TRIAL." Female Pelvic Medicine & Reconstructive Surgery 28(6): S8‐S9.
	Introduction: Pelvic organ prolapse (POP) can negatively affect the quality of life. Due to ageing, the number of women presenting with symptomatic POP will increase dramatically. Treatment options for moderate to severe POP are pessary and surgery. Currently, treatment selection is based on patients and physicians preference. Studies comparing pessary and surgery in a randomized setting are lacking. Therefore, we performed this multicenter randomized controlled trial (RCT) comparing both treatment modalities. Objective: To present the 1‐year interim results of a 2‐year RCT comparing the efficacy of pessary and surgery for women presenting with symptomatic POP. Methods: Multicenter RCT to prove non‐inferiority of pessary as compared to surgery, including women with symptomatic POP stage ≥2 and a successful pessary fitting procedure. The primary outcome was subjective improvement at 12‐months follow‐up, defined as responding 'very much' or 'much improvement' to the Patient Global Impression of Improvement (PGI‐I) questionnaire. Secondary outcomes included symptom bother measured with the Pelvic Floor Distress Inventory (PFDI‐20), adverse events and cross‐over of therapy. In the PFDI‐20, a higher score represents more bothersome symptoms. With 198 women per group, we would achieve 80% power to reject the null hypothesis that pessary therapy is inferior to surgery, with a 1‐sided alpha of 0.05 and a non‐inferiority margin of 10%. Analysis of the primary outcome was done using the Manning‐Farrington test for non‐inferiority for the difference between two proportions, against the non‐inferiority margin of 10% risk difference. Continuous data were analysed using the independent t‐test, with 95% confidence intervals (CI) estimated using bootstrapping. Results: A total of 439 women were included, 218 (49.7%) women in the pessary group and 221 (50.3%) women in the surgery group. A total of 96 (44.0%) women in the pessary group switched to surgery and in the surgery group resurgery was performed in 7 (3.2%) women and 2 (0.9%) women additionally used a pessary. In the intention‐to‐treat analysis, subjective improvement was reported by 75.9% of women in the pessary group and 82.3% in the surgery group (risk difference 6.3%; 90% CI ‐13.3% ‐ 0.6%; p‐value for non‐inferiority 0.20). Both groups showed an improvement on all subscales scores of the PFDI‐20, without significant difference between groups. In a per‐protocol analysis, subjective improvement was reported by 67.3% of women in the pessary group and 84.8% of women in the surgery group (risk difference 17.5%; 90% CI ‐26.1% ‐ ‐8.8%; p‐value for non‐inferiority 0.92). Additionally, the per‐protocol analysis showed that significantly more women in the surgery group gained a significantly greater reduction on the UDI‐6 scale (mean difference 5.6; 95% CI 0.4 ‐ 10.6; p‐value 0.02) and on the total PFDI‐20 scale (mean difference 11.3; 95%CI 1.0 ‐ 21.4; p‐value 0.03), as compared to the pessary group. Conclusions: For women presenting with symptomatic POP, surgery, as compared with initial pessary, results in higher rates of subjective improvement at 1‐year. Moreover, over 40% of women initially treated with a pessary was indicated for surgery within the first year. Our data showed that surgery should be considered as primary intervention for symptomatic POP.

Van Der Vaart, L., et al. (2022). "Sexual Functioning in Women with a Symptomatic Pelvic Organ Prolapse; A Multicenter Randomized Controlled Trial Between Pessary and Surgery." International Urogynecology Journal 33(Supplement 2): S261-S262.
	Introduction: Pelvic organ prolapse (POP) has a negative effect on female sexual functioning (FSF). Women with bothersome POP symptoms can be treated with either pessary or surgery. The effects on FSF have not been compared between women undergoing pessary and surgery as treatment for POP. We performed a multicenter randomized controlled trial (RCT) comparing both treatment modalities. This abstract refers to a planned secondary analysis of the RCT, namely the effect of pessary and surgery on FSF in women with POP, measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Objective(s): To present the 1-year interim results of a planned secondary analysis of a 2-year RCT comparing the improvement in FSF for both sexually active (SA) and sexually inactive women (NSA) who are treated with either pessary or surgery for symptomatic POP. Method(s): Multicenter RCT to prove non-inferiority, based on our primary outcome (the Patient Global Impression of Improvement scale), of pessary as compared to surgery. We included women with symptomatic POP stage >= 2 and a successful pessary fitting procedure. This abstract refers to the effect of both treatment modalities on the PISQ-IR. In the PISQ-IR, for sexually active (SA) women a higher score indicates better sexual functioning, for non-sexually active (NSA) women a higher score indicates a greater impact of POP on sexual inactivity. Secondary outcomes included a switch from sexual status and de novo dyspareunia. Categorical outcomes were analyzed using a Chi-squared, or Fisher's exact test as appropriate. Continuous data were analyzed using the independent t-test and we calculated the 95% confidence intervals (CI) using bootstrapping. Result(s): A total of 439 women were included, 218 (49.7%) women in the pessary group and 221 (50.3%) women in the surgery group. The intention-to-treat analysis showed that SA women in the surgery group reported statistically significant more improvement on the conditionimpact domain (mean difference -0.29; 95% CI -0.47 - -0.10, p <0.01) and the summary score (mean difference -0.08; 95% CI -0.17 - -0.01, p = 0.04) as compared to the pessary group. In the per-protocol analysis, SA women in the surgery group also reported more improvement on the condition-impact domain (mean difference -0.32; 95% CI -0.57 - -0.09, p<0.01) and the summary score (mean difference -0.13; 95% CI -0.23 - -0.03, p=0.02) as compared to the pessary group. No significant differences between pessary and surgery on the domains for NSA women were found. Eight (3.6%) women in the surgery group and 8 (3.7%) women in the pessary group developed de novo dyspareunia (p = 0.82). After surgery, women have 1.13 times higher odds (95% CI 0.5 - 2.7, p = 0.7) to become sexually active as compared to pessary. Conclusion(s): Surgery, in comparison with pessary therapy, resulted in significantly more improvement in sexual wellbeing in sexually active women undergoing an intervention for symptomatic POP. In non-sexually active women, both treatment modalities had similar effects on sexual functioning. Therefore, sexually active women who clearly express that POP-related symptoms limit their sexual functioning should be counseled that surgery results in a more remarkable improvement.

Van Der Vaart, L., et al. (2022). "SEXUAL FUNCTIONING IN WOMEN WITH A SYMPTOMATIC PELVIC ORGAN PROLAPSE; A MULTICENTER RANDOMIZED CONTROLLED TRIAL BETWEEN PESSARY AND SURGERY." Female Pelvic Medicine & Reconstructive Surgery 28(6): S66‐S67.
	Introduction: Pelvic organ prolapse (POP) has a negative effect on female sexual functioning (FSF). Women with bothersome POP symptoms can be treated with either pessary or surgery. The effects on FSF have not been compared between women undergoing pessary and surgery as treatment for POP. We performed a multicenter randomized controlled trial (RCT) comparing both treatment modalities. This abstract refers to a planned secondary analysis of the RCT, namely the effect of pessary and surgery on FSF in women with POP, measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA‐Revised (PISQ‐IR). Objective: To present the 1‐year interim results of a planned secondary analysis of a 2‐year RCT comparing the improvement in FSF for both sexually active (SA) and sexually inactive women (NSA) who are treated with either pessary or surgery for symptomatic POP. Methods: Multicenter RCT to prove non‐inferiority, based on our primary outcome (the Patient Global Impression of Improvement scale), of pessary as compared to surgery. We included women with symptomatic POP stage ≥2 and a successful pessary fitting procedure. This abstract refers to the effect of both treatment modalities on the PISQ‐IR. In the PISQ‐IR, for sexually active (SA) women a higher score indicates better sexual functioning, for non‐sexually active (NSA) women a higher score indicates a greater impact of POP on sexual inactivity. Secondary outcomes included a switch from sexual status and de novo dyspareunia. Categorical outcomes were analyzed using a Chi‐squared, or Fisher's exact test as appropriate. Continuous data were analyzed using the independent t‐test and we calculated the 95% confidence intervals (CI) using bootstrapping. Results: A total of 439 women were included, 218 (49.7%) women in the pessary group and 221 (50.3%) women in the surgery group. The intention‐to‐treat analysis showed that SA women in the surgery group reported statistically significant more improvement on the condition‐impact domain (mean difference ‐0.29; 95% CI ‐0.47 ‐ ‐0.10, p < 0.01) and the summary score (mean difference ‐0.08; 95% CI ‐0.17 ‐ ‐0.01, p = 0.04) as compared to the pessary group. In the per‐protocol analysis, SA women in the surgery group also reported more improvement on the condition‐impact domain (mean difference ‐0.32; 95% CI ‐ 0.57 ‐ ‐0.09, P < 0.01) and the summary score (mean difference ‐0.13; 95% CI ‐0.23 ‐ ‐0.03, P = 0.02) as compared to the pessary group. No significant differences between pessary and surgery on the domains for NSA women were found. Eight (3.6%) women in the surgery group and 8 (3.7%) women in the pessary group developed de novo dyspareunia (p = 0.82). After surgery, women have 1.13 times higher odds (95% CI 0.5 ‐ 2.7, p = 0.7) to become sexually active as compared to pessary. Conclusions: Surgery, in comparison with pessary therapy, resulted in significantly more improvement in sexual wellbeing in sexually active women undergoing an intervention for symptomatic POP. In non‐sexually active women, both treatment modalities had similar effects on sexual functioning. Therefore, sexually active women who clearly express that POP‐related symptoms limit their sexual functioning should be counseled that surgery results in a more remarkable improvement.

Van Dijk, M., et al. (2022). "Levothyroxine in Euthyroid Thyroid Peroxidase Antibody positive Women with Recurrent Pregnancy Loss: a multicentre, randomised, double-blind trial (T4LIFE trial)." Human reproduction (Oxford, England) 37: i12.
	Study question: Does levothyroxine treatment increase live birth rates in thyroid peroxidase antibodies (TPO‐Ab) positive women with recurrent pregnancy loss (RPL) and normal thyroid function? Summary answer: Levothyroxine treatment did not result in higher live birth rates in women with RPL positive for TPO‐Ab and a normal thyroid function, compared to placebo. What is known already: Women positive for TPO‐Ab have a higher risk of RPL. Levothyroxine supplementation has been proposed to reduce the risk of pregnancy complications. Evidence is limited whether levothyroxine treatment improves pregnancy outcomes in TPO‐Ab positive women with RPL. Study design, size, duration: We conducted an international double‐blind trial. Between January 2013 and September 2019, we randomly assigned 187 women to receive levothyroxine (94 women) or placebo (93 women). Before conception, women were randomly assigned in a 1:1 ratio to levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0.5 to 1.0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. Participants/materials, setting, methods: Patients with two or more pregnancy losses underwent diagnostic testing for RPL. Women with a normal TSH level and positive for TPO‐Ab were eligible for the study. Antiphospholipid syndrome was an exclusion criterion. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation. Secondary outcomes included ongoing pregnancy, pregnancy loss, preterm delivery, adverse events and time to conception leading to live birth. Main results and the role of chance: Live birth occurred in 47 women (50%) in the levothyroxine group and in 45 women (48%) in the placebo group (risk ratio, 1.03; 95% confidence interval [CI], 0.77 to 1.38; absolute risk difference 1.6%; 95% CI, ‐12.7% to 15.9%). There were no significant differences in any secondary outcomes. In both groups seven adverse events were reported, none of them directly related to the study procedure. Limitations, reasons for caution: The slow recruitment forced us to stop the trial prematurely. With this sample size we are not able to fully account for dropouts and the estimates have wide 95% confidence intervals. Detection of a difference of 5% in live birth rate would have required inclusion of more than 3000 women. Wider implications of the findings: Routine use of levothyroxine in women with RPL and normal thyroid function positive for TPO‐Ab is not recommended. Our results are in line with previous trials in TPO‐Ab positive women with a history of infertility or pregnancy loss or undergoing in vitro fertilization.

van Dijk Myrthe, M., et al. (2022). "Levothyroxine in euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss (T4LIFE trial): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial." The lancet. Diabetes & endocrinology 10(5): 322-329.
	Background: Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.; Methods: The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18-42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or β2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0·5-1·0 μg/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39.; Results: Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1·03 [95% CI 0·77 to 1·38]; absolute risk difference 1·6% [95% CI -12·7 to 15·9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure.; Interpretation: Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function.; Funding: Dutch Organization for Health Research and Development, Fonds NutsOhra, Dutch Patient Organization of Thyroid Disorders, the Jan Dekkerstichting and Dr Ludgardine Bouwmanstichting, and a personal donation through the Dutch Patient Organization of Thyroid Disorders.; Competing Interests: Declaration of interests MG received research and educational grants from Guerbet, Merck, and Ferring, not related to the presented work, paid to their institution. AH reports an unrestricted educational grant from Ferring, not related to the presented work, paid to their institution. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)

van Gemert, J., et al. (2022). "Endometrial polypectomy using tissue removal device or electrosurgical snare: a randomised controlled trial." Facts, views & vision in ObGyn 14(3): 235-243.
	Background: Hysteroscopic transcervical resection of endometrial polyps is a widely used method and is increasingly performed in office or outpatient care. To ensure patient comfort is key, smaller instruments are preferred while also achieving a complete resection of the pathology.; Objectives: To evaluate the effectiveness of the electrosurgical polyp snare (DPS) in comparison with a tissue removal device (TRD).; Materials and Methods: This was a randomised controlled non-inferiority trial which included 66 women with symptomatic endometrial polyps who had been referred to the gynaecological outpatient clinic at the Máxima Medical Centre, Veldhoven, the Netherlands. The patients were randomly allocated by using sealed envelopes to treatment with either the DPS (Duckbill®, Cook) or the TRD (Truclear™, Medtronic). Clinicians and patients were not blinded to the treatment performed. An independent observer blindly assessed the results.; Main Outcome Measures: The primary outcome was the complete removal of the endometrial polyp. Secondary outcomes were woman acceptability and pain during the procedure, operating time, peri-operative and immediate postoperative complications.; Results: 57% of the polyps in the DPS group and 95% in the TRD group were completely removed (risk difference -0.39; 95% CI: -0.60 to -0.15). Average operating time was longer with DPS compared to the TRD (11.7 min. vs. 6.8 min., p = 0.018). The number of insertions of the hysteroscope was higher with the DPS compared to the TRD (3.9 vs. 1.7, p <0.001). One serious adverse event, a uterine perforation, occurred in the DPS group.; Conclusion: The TRD was superior to the DPS in completeness of polyp removal.; What Is New?: TRD has a higher rate of complete polyp resection, overall safety and higher patient satisfaction, this instrument should be considered as the preferred option in outpatient and office gynaecology.

van Gorkom, G. N. Y., et al. (2019). "The effect of vitamin C (Ascorbic acid) in the treatment of patients with cancer: A systematic review." Nutrients 11(5): 977.
	Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.Copyright © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Van Gorp, T., et al. (2021). "ENGOT-EN11/GOG-3053/keynote-b21: phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with newly diagnosed high-risk endometrial cancer." International Journal of Gynecological Cancer 31(SUPPL 4): A72‐A73.
	Objectives Pembrolizumab, an anti‐PD‐1 antibody, has demonstrated activity as monotherapy and in combination with lenvatinib in patients with previously treated mismatch repair (MMR) deficient and MMR proficient endometrial cancer (EC). ENGOT‐en11/GOG‐3053/KEYNOTE‐B21 (NCT04634877) is a phase 3, randomized, double‐blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC. Methods Eligible patients are ≥18 years with newly diagnosed high‐risk (stage I/II non‐endometrioid or with p53 abnormality and any histology, stage III/IVa), previously untreated EC following surgery with curative intent with no evidence of disease post‐operatively. ∼990 patients will be randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles plus chemotherapy (carboplatin area under the curve [AUC] 5/ 6 plus paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2/2.7 plus paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2. Radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin‐EBRT vs EBRT vs no EBRT), histology (endometrioid vs non‐endometrioid), and FIGO surgical stage (I/II vs III/IVA). Dual primary endpoints are disease‐free survival (DFS; per investigator assessment) and OS. Secondary endpoints include DFS (per BICR), DFS (per investigator assessment) and OS by biomarker status (PD‐L1 and tumor mutational burden), safety, and QoL. Enrollment began December 2020 and is ongoing in 28 countries. Results Not applicable Conclusions Not applicable.

Van Gorp, T., et al. (2021). "ENGOT-en11/GOG-3053/KEYNOTEB21: phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with newly diagnosed high-risk endometrial cancer." Journal of Clinical Oncology 39(15 SUPPL).
	Background: Pembrolizumab, a selective humanized anti‐PD‐1 monoclonal antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% ORR as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer (EC). ENGOT‐en11/GOG3053/KEYNOTE‐B21 is a phase 3, randomized, double‐blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC. Methods: Eligible patients are ≥18 years old with newly diagnosed, histologically confirmed high‐risk (stage I/II non‐endometrioid, stage III/IVa, p53 abnormality) EC (carcinoma or carcinosarcoma) following surgery with curative intent with no evidence of disease post‐operatively or on imaging, and without prior systemic therapy/radiotherapy. In total,990 patients are randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles + chemotherapy (carboplatin area under the curve [AUC] 5 or 6 + paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2 or 2.7 + paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2 per their treatment assignment. At the investigator's discretion, radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatinEBRT vs EBRT vs no EBRT), histology (endometrioid vs non‐endometrioid), and International Federation of Gynecology and Obstetrics (FIGO) surgical stage (I/II vs III/IVA). Dual primary endpoints are disease‐free survival (DFS; per investigator assessment) and overall survival (OS), both estimated by the Kaplan‐Meier method, with a stratified log‐rank test to assess treatment differences and a Cox proportional hazard model with Efron's method of tie handling to assess the magnitude of treatment differences. Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD‐L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 [EORTC QLQ‐C30] and Endometrial Cancer Module [EORTC QLQEN24]). The study began enrollment in December 2020.

Van Gorp, T., et al. (2021). "ENGOT-EN11/GOG-3053/keynote-b21: phase 3 study of pembrolizumab or placebo + adjuvant chemotherapy ± radiotherapy for high-risk endometrial cancer." International Journal of Gynecological Cancer 31(SUPPL 1): A79‐A80.
	Introduction/Background Pembrolizumab, an anti‐PD‐1 antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% objective response rate [ORR] as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer. ENGOT‐en11/GOG‐3053/ KEYNOTE‐B21 (NCT04634877) is a phase 3, randomized, double‐blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with endometrial cancer. Methodology Eligible patients are ≥18 years old with newly diagnosed, high‐risk (stage I/II non‐endometrioid or with p53 abnormality and any histology, stage III/IVA), previously untreated endometrial cancer following surgery with curative intent with no evidence of disease post‐operatively. Approximately 990 patients are randomized to receive pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for 6 cycles plus chemotherapy (carboplatin area under the curve [AUC] 5/6 plus paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2/ 2.7 plus paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2. Radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin‐EBRT vs EBRT vs no EBRT), histology (endometrioid vs non‐endometrioid), and International Federation of Gynecology and Obstetrics surgical stage (I/II vs III/ IVA). Dual primary endpoints are disease‐free survival (DFS; per investigator assessment) and overall survival (OS). Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD‐L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0), and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 [EORTC QLQ‐C30] and Endometrial Cancer Module [EORTC QLQEN24]). Enrolment began December 2020 and is ongoing at 221 sites in 28 countries. Result(s) N/A Conclusion N/A.

Van Hoe, K., et al. (2021). "Lithium use in women with bipolar disorder during peripartum." Lithiumgebruik bij vrouwen met een bipolaire stoornis tijdens het peripartum. 63(7): 557-564.
	(Dutch) Achtergrond: Lithiumgebruik tijdens het peripartum vergt een zorgvuldige afweging wegens het risico op teratogene effecten, het ongunstige bijwerkingenprofiel en het risico op neonatale complicaties. Gezien de effectiviteit van lithium kan het gebruik tijdens het peripartum evenwel geindiceerd zijn. Doel: Overzicht bieden van de huidige evidentie betreffende het klinisch gebruik van lithium tijdens het peripartum, inclusief terugvalrisico in geval van (dis)continuatie en over het verloop van lithiumspiegels. Methode: Een literatuuronderzoek in de Medline- en ScienceDirect-database. Resultaten: Tien studies werden geincludeerd. Zes studies betroffen het terugvalrisico in geval van (dis)continuatie van lithium tijdens het peripartum. Vier studies betroffen het verloop van lithiumspiegels gedurende het peripartum. Stoppen met lithium tijdens de zwangerschap leidt tot een verhoogd terugvalrisico tijdens zwangerschap en post partum. Bij eenzelfde dosis zijn de lithiumspiegels in alle trimesters lager dan preconceptioneel. Conclusie: Voor- en nadelen van lithiumgebruik tijdens het peripartum dient men nauwgezet te overwegen, indien mogelijk preconceptioneel. Nauwgezette controle van maternale lithiumspiegels en nierfunctie is noodzakelijk wegens belangrijke fluctuaties tijdens het peripartum. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

van Hoeve, J. C., et al. (2020). "Effects of oncological care pathways in primary and secondary care on patient, professional and health systems outcomes: a systematic review and meta-analysis." Systematic Reviews 9(1): 246.
	Background: Pathways are frequently used to improve care for cancer patients. However, there is little evidence about the effects of pathways used in oncological care. Therefore, we performed a systematic review and meta-analysis aiming to identify and synthesize existing literature on the effects of pathways in oncological care. Method(s): All patients diagnosed with cancer in primary and secondary/tertiary care whose treatment can be characterized as the strategy "care pathways" are included in this review. A systematic search in seven databases was conducted to gather evidence. Studies were screened by two independent reviewers. Study outcomes regarding patients, professionals, and system level were extracted from each study. Result(s): Out of 13,847 search results, we selected 158 articles eligible for full text assessment. One hundred fifty studies were excluded and the remaining eight studies represented 4786 patients. Most studies were conducted in secondary/tertiary care. Length of stay (LOS) was the most common used indicator, and was reported in five studies. Meta-analysis based on subgroups showed an overall shorter LOS regarding gastric cancer (weighted mean difference (WMD)): - 2.75, CI: - 4.67 to - 0.83) and gynecological cancer (WMD: - 1.58, CI: - 2.10 to - 1.05). Costs were reported in six studies and most studies reported lower costs for pathway groups. Conclusion(s): Despite the differences between the included studies, we were able to present an evidence base for cancer care pathways performed in secondary/tertiary care regarding the positive effects of LOS in favor of cancer care pathways. Systematic review registration: PROSPERO CRD42017057592.Copyright © 2020, The Author(s).

van Hoogenhuijze, N. E., et al. (2021). "Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)." Human reproduction (Oxford, England) 36(1): 87-98.
	STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The therlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER: Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE: 31 July 2015. DATE OF FIRST PATIENT’S ENROLMENT: 26 January 2016.

van Hoogenhuijze, N. E., et al. (2022). "Economic evaluation of endometrial scratching before the second IVF/ICSI treatment: a cost-effectiveness analysis of a randomized controlled trial (SCRaTCH trial)." Human reproduction (Oxford, England) 37(2): 254-263.
	Study Question: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period?; Summary Answer: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution.; What Is Known Already: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth.; Study Design, Size, Duration: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed.; Participants/materials, Setting, Methods: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK).; Main Results and the Role of Chance: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth.; Limitations, Reasons for Caution: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now.; Wider Implications of the Findings: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRa

van Hoogenhuijze Nienke, E., et al. (2023). "Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis." Human Reproduction Update 29(6): 721-740.
	Background: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed.; Objective and Rationale: This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis.; Search Methods: A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET.; Outcomes: Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause.; Wider Implications: This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

van Kessel, M., et al. (2021). "Transvaginal hydrolaparoscopy versus hysterosalpingography in the work-up for subfertility: a randomized controlled trial." Reproductive Biomedicine Online 43(2): 239‐245.
	Research question: Is transvaginal hydrolaparoscopy (THL) non‐inferior to hysterosalpingography (HSG) as a first‐line tubal patency test in subfertile women in predicting the chance of conception leading to live birth? Design: A multicentre, randomized controlled trial in four teaching hospitals in the Netherlands, which randomized subfertile women scheduled for tubal patency testing to either THL or HSG as a first‐line tubal patency test. The primary outcome was conception leading to live birth within 24 months after randomization. Results: A total of 149 women were randomized to THL and 151 to HSG. From the intention‐to‐treat population, 83 women from the THL group (58.5%) conceived and delivered a live born child within 24 months after randomization compared with 82 women (55.4%) in the HSG group (difference 3.0%, 95% CI –8.3 to 14.4). Time to conception leading to live birth was not statistically different between groups. Miscarriage occurred in 16 (11.3%) women in the THL group, versus 20 (13.5%) women in the HSG group (RR = 0.66, 95% CI 0.34 to 1.32, P = 0.237), and multiple pregnancies occurred in 12 (8.4%) women in the THL group compared with 19 (12.8%) women in the HSG group (RR = 0.84, 95% CI 0.46 to 1.55, P = 0.58). Ectopic pregnancy was diagnosed in two women in the HSG group (1.4%) and none in the THL group (P = 0.499). Conclusion: In a preselected group of subfertile women with a low risk of tubal pathology, use of THL was not inferior to HSG as a first‐line test for predicting conception leading to live birth.

van Kessel, M. A., et al. (2022). "Fertility-related quality of life in subfertile women undergoing tubal testing with transvaginal hydrolaparoscopy or hysterosalpingography." European Journal of Obstetrics, Gynecology, and Reproductive Biology 274: 19-22.
	OBJECTIVE: Both subfertility and its management can have significant impact on quality of life (QoL). Tubal patency testing as part of the fertility work-up, is considered to cause more physical complaints and stress than other tests. Pain scores for HSG are higher than for THL, but acceptability of the procedures was found to be comparable. Fertility-related QoL has not yet been studied in women undergoing tubal patency testing. STUDY DESIGN: We performed a standardized questionnaire study alongside a previously reported randomized controlled trial comparing THL and HSG in subfertile women, in which 24-month live birth rates occurred in 58.5% versus 55.4%, respectively. We randomly assigned 300 subfertile women to THL or HSG between May 2013 and October 2016. Women were eligible if they were undergoing a fertility work-up with an indication for evaluation of tubal patency. Fertility-related QoL was measured six weeks after the procedure with the validated FertiQoL questionnaire. The scores for the Core scale and subscales between THL and HSG were compared using Mann-Whitney-U test and multiple linear regression analysis. RESULTS: The questionnaire was completed by 84 women in the THL group (56%) and 96 women in the HSG group (64%). Core scores were 74.6 ± 12.8 for THL and 73.4 ± 12.4 for HSG (p = 0.39). Scores for the Emotional domain were 64.5 ± 19.0 for THL versus 66.0 ± 16.3 (p = 0.67) for HSG. Scores for the 'Mind-body' domain for THL were 76.9 ± 15.6 versus 74.1 ± 18.0 for HSG (p = 0.42), while scores for the Relational domain were 79.2 ± 12.9 for THL and 76.9 ± 15.6 for HSG (p = 0.21). Scores for the Social domain for THL were 77.9 ± 15.1 versus 76.7 ± 14.1, (p = 0.42). The multiple linear regression analysis showed only a statistical significant positive effect of older age on the score for the Emotional domain (p = 0.015). CONCLUSION: In a preselected group of women with low risk for tubal pathology we did not find differences in fertility-related QoL between tubal patency testing with THL versus HSG.

van Kessel, M. A., et al. (2022). "The cost-effectiveness of transvaginal hydrolaparoscopy versus hysterosalpingography in the work-up for subfertility." Human Reproduction 37(12): 2768-2776.
	STUDY QUESTION: Is a strategy starting with transvaginal hydrolaparoscopy (THL) cost-effective compared to a strategy starting with hysterosalpingography (HSG) in the work-up for subfertility? SUMMARY ANSWER: A strategy starting with THL is cost-effective compared to a strategy starting with HSG in the work-up for subfertile women. WHAT IS KNOWN ALREADY: Tubal pathology is a common cause of subfertility and tubal patency testing is one of the cornerstones of the fertility work-up. Both THL and HSG are safe procedures and can be used as a first-line tubal patency test. STUDY DESIGN, SIZE, DURATION: This economic evaluation was performed alongside a randomized clinical trial comparing THL and HSG in 300 subfertile women, between May 2013 and October 2016. For comparisons of THL and HSG, the unit costs were split into three main categories: costs of the diagnostic procedure, costs of fertility treatments and the costs for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subfertile women scheduled for tubal patency testing were eligible. Women were randomized to a strategy starting with THL or a strategy starting with HSG. The primary outcome of the study was conception leading to a live birth within 24 months after randomization. The mean costs and outcomes for each treatment group were compared. We used a non-parametric bootstrap resampling of 1000 re-samples to investigate the effect of uncertainty and we created a cost-effectiveness plane and cost-effectiveness acceptability curves. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 149 women to THL and 151 to HSG, and we were able to achieve complete follow-up of 142 versus 148 women, respectively. After the fertility work-up women were treated according to the Dutch guidelines and based on a previously published prognostic model. In the THL group, 83 women (58.4%) conceived a live born child within 24 months after randomization compared to 82 women (55.4%) in the HSG group (difference 3.0% (95% CI: -8.3 to 14.4)). The mean total costs per woman were lower in the THL group compared to the HSG group (THL group e4991 versus e5262 in the HSG group, mean cost difference 1/4 -e271 (95% CI -e273 to -e269)). Although the costs of only the diagnostic procedure were higher in the THL group, in the HSG group more women underwent diagnostic and therapeutic laparoscopies and also had higher costs for fertility treatments. LIMITATIONS, REASONS FOR CAUTION: Our trial was conducted in women with a low risk of tubal pathology; therefore, the results of our study are not generalizable to women with high risk of tubal pathology. Furthermore, this economic analysis was based on the Dutch healthcare system, and possibly our results are not generalizable to countries with different strategies or costs for fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: After 2 years of follow-up, we found a live birth rate of 58.4% in the THL group versus 55.4% in the HSG group and a lower mean cost per woman in the THL group, with a cost difference of -e271. The findings of our trial suggest that a strategy starting with THL is cost-effective compared to a strategy starting with HSG in the workup for subfertile women. However, the cost difference between the two diagnostic strategies is limited compared to the total cost per woman in our study and before implementing THL as a first-line strategy for tubal patency testing, more research in other fields, such as patient preference and acceptance, is necessary.Copyright VC The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved.

van Kol, K., et al. (2021). "Adjuvant Hysterectomy for Cervical Cancer Patients Treated with Chemoradiation Therapy: A Systematic Review on the Pathology-Proven Residual Disease Rate." Cancers 13(24).
	Objective: To determine the incidence of pathology-proven residual disease in adjuvant hysterectomy specimens in patients with cervical cancer, treated with chemoradiation therapy. Secondly, to assess a possible association for pathology-proven residual disease regarding the time between chemoradiation therapy and adjuvant hysterectomy. Additionally, the survival rate and complication rate were assessed.; Methods: PubMed, EMBASE, and the Cochrane database were searched from inception up to 8 March 2021.; Results: Of the 4601 screened articles, eleven studies were included. A total of 1205 patients were treated with chemoradiation therapy and adjuvant hysterectomy, ranging from three to twelve weeks after chemoradiation therapy. A total of 411 out of 1205 patients (34%) had pathology-proven residual disease in the adjuvant hysterectomy specimen. There was no association found in the time between chemoradiation therapy and adjuvant hysterectomy. Follow-up ranged from 2.4 to 245 months, during which 270 patients (22%) relapsed, and 298 patients (27%) were deceased. A total of 202 (35%) complications were registered in 578 patients.; Conclusion: there is no association found in the time between chemoradiation therapy and residual disease on adjuvant hysterectomy specimens. The survival rates after chemoradiation therapy and adjuvant hysterectomy are suboptimal, while the risk of complications after adjuvant hysterectomy is high.

van Kol, K. G. G., et al. (2019). "Abdominal radical trachelectomy versus chemotherapy followed by vaginal radical trachelectomy in stage 1B2 (FIGO 2018) cervical cancer. A systematic review on fertility and recurrence rates." Gynecologic Oncology 155(3): 515-521.
	Introduction: There is currently no standard of care for women with cervical cancer stage IB2 (FIGO 2018, ≥2 cm and <4 cm in greatest dimension) who wish to preserve their fertility. Generally, two approaches are offered. Option 1: neoadjuvant platinum-based chemotherapy (NACT) to reduce the tumor size to ≤ 2 cm, followed by Vaginal Radical Trachelectomy (VRT) with Pelvic Lymph Node Dissection (PLND) either before chemotherapy or at the time of VRT. Option 2: Abdominal Radical Trachelectomy (ART) with PLND.; Objective: To compare rates of fertility, pregnancy, life births as well as recurrence for women with cervical cancer stage IB2 treated with either NACT followed by VRT, or ART.; Methods: A systematic review was performed using the PubMed database. Articles reporting the search term 'trachelectomy' as text word or as Medical Subject Headings (MeSH) were identified.; Results: Ten studies were identified with a total of 338 patients. After NACT followed by VRT 39% of the women tried to conceive, 70% of these women got pregnant, of which 63% resulted in a life birth. The overall recurrence and death rate were 10% and 2.9% respectively. After ART 40% of the women tried to conceive, 21% of these women got pregnant, which resulted in a life birth rate of 42%. Recurrence and death rate after ART were 6.9%, and 3.4% respectively.; Conclusion: Women with cervical cancer stage IB2 and a wish to preserve fertility treated with NACT followed by VRT have a significantly higher chance of pregnancy than women treated with ART, with comparative oncological results. (Copyright © 2019 Elsevier Inc. All rights reserved.)

van Lieshout Laura, A. M., et al. (2019). "Hysterectomy with opportunistic salpingectomy versus hysterectomy alone." The Cochrane Database of Systematic Reviews 8: CD012858.
	Background: Ovarian cancer has the highest mortality rate of all gynaecological malignancies with an overall five-year survival rate of 30% to 40%. In the past two decades it has become apparent and more commonly accepted that a majority of ovarian cancers originate in the fallopian tube epithelium and not from the ovary itself. This paradigm shift introduced new possibilities for ovarian cancer prevention. Salpingectomy during a hysterectomy for benign gynaecological indications (also known as opportunistic salpingectomy) might reduce the overall incidence of ovarian cancer. Aside from efficacy, safety is of utmost importance, especially due to the preventive nature of opportunistic salpingectomy. Most important are safety in the form of surgical adverse events and postoperative hormonal status. Therefore, we compared the benefits and risks of hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy.; Objectives: To assess the effect and safety of hysterectomy with opportunistic salpingectomy versus hysterectomy without salpingectomy for ovarian cancer prevention in women undergoing hysterectomy for benign gynaecological indications; outcomes of interest include the incidence of epithelial ovarian cancer, surgery-related adverse events and postoperative ovarian reserve.; Search Methods: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two clinical trial registers were searched in January 2019 together with reference checking and contact with study authors.; Selection Criteria: We intended to include both randomised controlled trials (RCTs) and non-RCTs that compared ovarian cancer incidence after hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For assessment of surgical and hormonal safety, we included RCTs that compared hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications.; Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were ovarian cancer incidence, intraoperative and short-term postoperative complication rate and postoperative hormonal status. Secondary outcomes were total surgical time, estimated blood loss, conversion rate to open surgery (applicable only to laparoscopic and vaginal approaches), duration of hospital admission, menopause-related symptoms and quality of life.; Main Results: We included seven RCTs (350 women analysed). The evidence was of very low to low quality: the main limitations being a low number of included women and surgery-related adverse events, substantial loss to follow-up and a large variety in outcome measures and timing of measurements.No studies reported ovarian cancer incidence after hysterectomy with opportunistic salpingectomy compared to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For surgery-related adverse events, there were insufficient data to assess whether there was any difference in both intraoperative (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.11 to 3.94; 5 studies, 286 participants; very low-quality evidence) and short-term postoperative (OR 0.13, 95% CI 0.01 to 2.14; 3 studies, 152 participants; very low-quality evidence) complication rates between hysterectomy with opportunistic salpingectomy and hysterectomy without opportunistic salpingectomy because the number of surgery-related adverse events was very low. For postoperative hormonal status, the results were compatible with no difference, or with a reduction in anti-Müllerian hormone (AMH) that would not be clinically relevant (mean difference (MD) -0.94, 95% CI -1.89 to 0.01; I 2 = 0%; 5 studies, 283 participants; low-quality evidence). A reduction in AMH would be unfavourable, but due to wide CIs, the posto erative change in AMH can still vary from a substantial decrease to even a slight increase.; Authors' Conclusions: There were no eligible studies reporting on one of our primary outcomes - the incidence of ovarian cancer specifically after hysterectomy with or without opportunistic salpingectomy. However, outside the scope of this review there is a growing body of evidence for the effectiveness of opportunistic salpingectomy itself during other interventions or as a sterilisation technique, strongly suggesting a protective effect. In our meta-analyses, we found insufficient data to assess whether there was any difference in surgical adverse events, with a very low number of events in women undergoing hysterectomy with and without opportunistic salpingectomy. For postoperative hormonal status we found no evidence of a difference between the groups. The maximum difference in time to menopause, calculated from the lower limit of the 95% CI and the natural average AMH decline, would be approximately 20 months, which we consider to be not clinically relevant. However, the results should be interpreted with caution and even more so in very young women for whom a difference in postoperative hormonal status is potentially more clinically relevant. Therefore, there is a need for research on the long-term effects of opportunistic salpingectomy during hysterectomy, particularly in younger women, as results are currently limited to six months postoperatively. This limit is especially important as AMH, the most frequently used marker for ovarian reserve, recovers over the course of several months following an initial sharp decline after surgery. In light of the available evidence, addition of opportunistic salpingectomy should be discussed with each woman undergoing a hysterectomy for benign indication, with provision of a clear overview of benefits and risks.

Van Lieshout, R. (2022). "Online Peer-Delivered Group CBT for PPD." ClinicalTrials.gov.
	No Results Available Behavioral: Cognitive Behavioural Therapy (CBT) Edinburgh Postnatal Depression Scale (EPDS)|MINI International Neuropsychiatric Interview|GAD-7|Multidimensional Scale of Perceived Social Support (MSPSS)|The Postpartum Bonding Questionnaire (PBQ)|Infant Behavior Questionnaire-Revised Very Short Form (IBQ-R)|EQ-5D-5L|Healthcare Resource Utilization Questionnaire Female Not Applicable 167 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment OnlinePeerCBT October 2024

Van Lieshout Ryan, J., et al. (2020). "Public health nurse delivered group cognitive behavioral therapy (CBT) for postpartum depression: A pilot study." Public health nursing (Boston, Mass.) 37(1): 50-55.
	Objectives: Although postpartum depression (PPD) affects 1 in 5 women, just 15% receive treatment. Cognitive Behavioural Therapy (CBT) is a first-line treatment for PPD. The objective of this pilot study was to determine the feasibility and acceptability of public health nurse (PHN)-delivered group CBT for PPD and to determine preliminary estimates of effect.; Design: A pre-posttest design was used. Participants provided data before and after the CBT groups.; Sample: Seven women who were over the age of 18 and had given birth in the past year participated.; Measurements: Feasibility and acceptability focused on PHN training, recruitment, retention, and adherence to the intervention. Participants provided data on depression, worry, health care utilization and mother-infant relations. Women and their partners reported on infant temperament.; Intervention: Participants attended a 9-week CBT group delivered by two PHNs.; Results: The PHN training, CBT intervention and our study protocol were found to be feasible and acceptable to participants. Reductions were seen in depression and worry. The number of health care visits decreased; mother-infant relations improved.; Conclusions: These findings highlight the feasibility of PHN-delivered group CBT for PPD and suggest that it could reduce the burden of PPD on women and their children. (© 2019 Wiley Periodicals, Inc.)

Van Niekerk, L., et al. (2019). "Psychological interventions for endometriosis-related symptoms: a systematic review with narrative data synthesis." Archives of Women's Mental Health 22(6): 723-735.
	Endometriosis impacts the physical, psychological and quality of life domains of women. Despite the medical and/or surgical management of endometriosis, the presence of persistent pelvic pain and psychological distress often continues, suggesting a role for psychological interventions in treatment planning. The present study aimed to conduct the first systematic review, with narrative data synthesis, on psychological interventions for endometriosis-related symptoms. The study also aimed to determine the effectiveness of current interventions in resolving psychological and pain-related loss of function associated with endometriosis and to identify gaps in the literature requiring further research. A total of 15,816 studies were retrieved through database searching and handsearching, with two researchers identifying 11 full-text studies that met inclusion criteria. Three studies of 'moderate' quality were identified, although the overall quality of studies was found to be 'weak', with a 'high' risk of bias. The findings regarding the effectiveness of psychological interventions for endometriosis-related symptoms remain inconclusive. Further research into psychological interventions for women with endometriosis that employ evidence-based protocols with high intervention integrity is recommended.

Van Oudheusden, A., et al. (2022). "Laparoscopic Sacrocolpopexy versus Open Abdominal Sacrocolpopexy for Vaginal Vault Prolapse: Long-term Follow-up of a Randomized Trial." International Urogynecology Journal 33(Supplement 2): S240-S241.
	Introduction: The prevalence of vaginal vault prolapse, requiring apical surgery, has been reported in 23% of women who underwent vaginal hysterectomy for pelvic organ prolapse (POP). Sacrocolpopexy is one of the preferred surgical treatment options. A previously conducted randomized controlled trial compared laparoscopic sacrocolpopexy (LSC) to abdominal sacrocolpopexy (ASC) as treatment for vaginal vault prolapse. The results showed less blood loss, a shorter hospital stay, and less related morbidity in favor of the laparoscopic group, after 12 months of follow-up. There was a significant improvement in quality of life in both groups. Recognition of long-term outcomes is essential for giving consensus regarding optimal surgical treatment and for adequate patient selection and preoperative counselling. Objective(s): To evaluate long-term outcomes in patients with vaginal vault prolapse, who underwent a laparoscopic sacrocolpopexy or abdominal sacrocolpopexy in our previously conducted randomized controlled trial Methods: All patients from the initial trial were asked for participation in a long-term follow-up study. They were asked to fill in several Dutch questionnaires and visit our outpatient clinic for pelvic examination. Primary outcome was the long-term disease specific quality of life, measured with the Urogenital Distress Inventory. Secondary outcomes include the effects of the surgical treatment on POP-related functional symptoms as micturition and defecation, measured with the Urogenital Distress Inventory, Defecatory Distress Inventory, and Incontinence Impact Questionnaire. Patient satisfaction of their postoperative condition as compared to how it was before surgery was verified by the Patient Global Impression of Improvement. Anatomical outcomes were measured with the POP-Q examination. Result(s): In the original trial 74 women were randomly assigned to laparoscopic sacrocolpopexy (n=37) or abdominal sacrocolpopexy (n=37) between 2007 and 2012. We analyzed 22 patients in the LSC group and 19 patients in the ASC group, with a median follow-up duration of 105 months (8.75 years) and 111 months (9.25 years), respectively (p=.856). Health related quality of life did not differ after long-term follow-up with median scores of 0.0 on the 'genital prolapse' domain of the UDI in both groups (IQR 0 - 17 for LSC and IQR 0 - 0 for ASC; p=.175). Patient satisfaction, according to the PGI-I questionnaire was also not statistically different (LSC 57.9%; ASC 58.8%; p=.317). Anatomical outcomes were the same for both groups on all points of the POP-Q. Point C on the POP-Q examination showed a mean score of -4.7 in the LSC group and a mean score of -5.8 in the ASC group (range -8 - 8 for LSC and range -8 - -3 for ASC; p=.353). Conclusion(s): Results of early follow-up provided evidence in favor of the laparoscopic approach. After long-term follow-up, laparoscopic sacrocolpopexy and abdominal sacrocolpopexy show no differences on health related quality of life and anatomical outcome measures.

Van Oudheusden, A., et al. (2022). "LAPAROSCOPIC SACROCOLPOPEXY VERSUS OPEN ABDOMINAL SACROCOLPOPEXY FOR VAGINALVAULT PROLAPSE: LONGTERM FOLLOW-UP OF A RANDOMIZED TRIAL." Female Pelvic Medicine and Reconstructive Surgery 28(6 Supplement 1): S50.
	Introduction: The prevalence of vaginal vault prolapse, requiring apical surgery, has been reported in 23% of women who underwent vaginal hysterectomy for pelvic organ prolapse (POP). Sacrocolpopexy is one of the preferred surgical treatment options. A previously conducted randomized controlled trial compared laparoscopic sacrocolpopexy (LSC) to abdominal sacrocolpopexy (ASC) as treatment for vaginal vault prolapse. The results showed less blood loss, a shorter hospital stay, and less related morbidity in favor of the laparoscopic group, after 12 months of follow-up. There was a significant improvement in quality of life in both groups. Recognition of long-term outcomes is essential for giving consensus regarding optimal surgical treatment and for adequate patient selection and preoperative counselling. Objective(s): To evaluate long-term outcomes in patients with vaginal vault prolapse, who underwent a laparoscopic sacrocolpopexy or abdominal sacrocolpopexy in our previously conducted randomized controlled trial. Method(s): All patients from the initial trial were asked for participation in a long-term follow-up study. They were asked to fill in several Dutch questionnaires and visit our outpatient clinic for pelvic examination. Primary outcome was the long-term disease specific quality of life, measured with the Urogenital Distress Inventory. Secondary outcomes include the effects of the surgical treatment on POP-related functional symptoms as micturition and defecation, measured with the Urogenital Distress Inventory, Defecatory Distress Inventory, and Incontinence Impact Questionnaire. Patient satisfaction of their postoperative condition as compared to how it was before surgery was verified by the Patient Global Impression of Improvement. Anatomical outcomes were measured with the POP-Q examination. Result(s): In the original trial 74 women were randomly assigned to laparoscopic sacrocolpopexy (n = 37) or abdominal sacrocolpopexy (n = 37) between 2007 and 2012. We analyzed 22 patients in the LSC group and 19 patients in the ASC group, with a median follow-up duration of 105 months (8.75 years) and 111 months (9.25 years), respectively (P = .856). Health related quality of life did not differ after long-term follow-up with median scores of 0.0 on the 'genital prolapse' domain of the UDI in both groups (IQR 0 - 17 for LSC and IQR 0 - 0 for ASC; P = .175). Patient satisfaction, according to the PGI-I questionnaire was also not statistically different (LSC 57.9%; ASC 58.8%; P = .317). Anatomical outcomes were the same for both groups on all points of the POP-Q. Point C on the POP-Q examination showed a mean score of - 4.7 in the LSC group and a mean score of -5.8 in the ASC group (range -8 - 8 for LSC and range -8 - -3 for ASC; P = .353). Conclusion(s): Results of early follow-up provided evidence in favor of the laparoscopic approach. After long-term follow-up, laparoscopic sacrocolpopexy and abdominal sacrocolpopexy show no differences on health related quality of life and anatomical outcome measures.

van Poppel, M. N. M., et al. (2022). "Interaction between rs10830962 polymorphism in MTNR1B and lifestyle intervention on maternal and neonatal outcomes: secondary analyses of the DALI lifestyle randomized controlled trial." American journal of clinical nutrition 115(2): 388‐396.
	BACKGROUND: Interactions between polymorphisms of the melatonin receptor 1B (MTNR1B) gene and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or the healthy eating intervention is unknown. OBJECTIVES: The aim was to assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy. METHODS: Women with a BMI (in kg/m2) of ≥29 (n = 436) received counseling on healthy eating (HE), physical activity (PA), or both. The control group received usual care. This secondary analysis had a factorial design with comparison of HE compared with no HE and PA compared with no PA. Maternal outcomes at 24‐28 wk were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA‐IR), disposition index, and development of GDM. Neonatal outcomes were cord blood leptin and C‐peptide and estimated neonatal fat percentage. The interaction between receiving either the HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis. RESULTS: GDM risk was increased in women homozygous for the G allele of rs10830962 (OR: 2.60; 95% CI: 1.34, 5.06) or rs10830963 (OR: 2.83; 95% CI: 1.24, 6.47). Significant interactions between rs10830962 and interventions were found: in women homozygous for the G allele but not in the other genotypes, the PA intervention reduced maternal fasting insulin (β: ‐0.16; 95% CI: ‐0.33, 0.02; P = 0.08) and HOMA‐IR (β: ‐0.17; 95% CI: ‐0.35, 0.01; P = 0.06), and reduced cord blood leptin (β: ‐0.84; 95% CI: ‐1.42, ‐0.25; P = 0.01) and C‐peptide (β: ‐0.62; 95% CI: ‐1.07, ‐0.17; P = 0.01). In heterozygous women, the HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (β: ‐1.6 kg; 95% CI: ‐2.4, ‐0.8 kg). No interactions were found. CONCLUSIONS: In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance, cord blood C‐peptide, and cord blood leptin.

van Reijn-Baggen Daniëlle, A., et al. (2022). "Pelvic Floor Physical Therapy for Pelvic Floor Hypertonicity: A Systematic Review of Treatment Efficacy." Sexual Medicine Reviews 10(2): 209-230.
	Introduction: Hypertonicity of the pelvic floor (PFH) is a disabling condition with urological, gynecological and gastrointestinal symptoms, sexual problems and chronic pelvic pain, impacting quality of life. Pelvic floor physical therapy (PFPT) is a first-line intervention, yet no systematic review on the efficacy of PFPT for the treatment of PFH has been conducted.; Objectives: To systematically appraise the current literature on efficacy of PFPT modalities related to PFH.; Methods: PubMed, Embase, Emcare, Web of Science, and Cochrane databases were searched from inception until February 2020. A manual search from reference lists of included articles was performed. Ongoing trials were reviewed using clinicaltrial.gov. Randomized controlled trials (RCTs), prospective - and retrospective cohorts and case-study analyses were included. Outcome measures were pelvic floor muscle tone and function, pain reports, sexual function, pelvic floor symptom scores, quality of life and patients' perceived effect.; Results: The literature search resulted in 10 eligible studies including 4 RCTs, 5 prospective studies, and 1 case study published between 2000 and 2019. Most studies had a high risk of bias associated with the lack of a comparison group, insufficient sample sizes and non-standardized interventions. Six studies were of low and 4 of medium quality. All studies were narratively reviewed. Three of 4 RCTs found positive effects of PFPT compared to controls on five out of 6 outcome measures. The prospective studies found significant improvements in all outcome measures that were assessed. PFPT seems to be efficacious in patients with chronic prostatitis, chronic pelvic pain syndrome, vulvodynia, and dyspareunia. Smallest effects were seen in patients with interstitial cystitis and painful bladder syndrome.; Conclusion: The findings of this systematic review suggest that PFPT can be beneficial in patients with PFH. Further high-quality RCTs should be performed to confirm the effectiveness of PFPT in the treatment of PFH. van Reijn-Baggen DA, Han-Geurts IJM, Voorham-van der Zalm PJ, et al. Pelvic Floor Physical Therapy for Pelvic Floor Hypertonicity: A Systematic Review of Treatment Efficacy. Sex Med Rev 2022;10:209-230. (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Van Stein, R., et al. (2022). "EVALUATION OF EXTERNAL VALIDITY OF THE OVHIPEC-1 TRIAL IN A REAL-WORLD POPULATION." International Journal of Gynecological Cancer 32(Supplement 3): A173-A174.
	Objectives The OVHIPEC-1 trial showed improved overall survival (OS) and recurrence-free survival when interval cytoreductive surgery (CRS) was combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in women with stage III epithelial ovarian cancer (EOC). We compared the trial population to a real-world population diagnosed and treated during the same period to explore the generalizability of the trial results. Methods All patients undergoing interval CRS between 2007- 2016 were identified from the nationwide Netherlands Cancer Registry if they fulfilled the key eligibility criteria of OVHIPEC- 1. We compared patient and treatment characteristics, and OS between the control arm of the trial and the realworld population. Results The distribution of age, comorbidity, BRCA-status, histologic subtype, and completeness of CRS were similar in trial and non-trial patients. The trial population had a better performance status and a higher socioeconomic status compared to the real-world population. Trial patients underwent bowel surgery more often. The vast majority of patients received 6 cycles of chemotherapy. In real-world setting, patients received more often >6 cycles. The difference in OS between the trial and the real-world population was not statistically significant (figure 1). Conclusions Despite differences in patient and treatment characteristics, OS of patients treated in the control arm of OVHIPEC- 1 was similar to patients treated outside the trial. This finding does not lend support for the hypothesis that the survival benefit seen in the trial was caused by inferior outcome of patients selected for the trial. These results support the administration of HIPEC in stage III EOC patients undergoing interval CRS in clinical practice. (Figure Presented).

van Stein Ruby, M., et al. (2023). "Evaluation of external validity of the OVHIPEC-1 trial in a real-world population." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 161(2): 640-648.
	Objective: The OVHIPEC-1 trial (Phase III randomised clinical trial for stage III ovarian carcinoma randomising between interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy) showed improved survival when interval cytoreductive surgery (CRS) was combined with hyperthermic intraperitoneal chemotherapy in patients with stage III epithelial ovarian cancer (EOC). The authors compared the control arm of the trial with a real-world population treated in the Netherlands during the same period to explore generalizability of the trial results.; Methods: For this nationwide comparative cohort study, all patients with EOC undergoing interval CRS between 2007 and 2016 were identified from the Netherlands Cancer Registry if they fulfilled the eligibility criteria of OVHIPEC-1 (n = 1376). Patient and treatment characteristics, and overall survival (OS) were compared between trial and real-world populations.; Results: Age, comorbidity, BRCA status, histologic subtype, and residual disease were similar in trial and real-world patients. Trial patients had a better performance status, higher socioeconomic status, and underwent bowel surgery more often. In a real-world setting, patients more often received more than six cycles. The difference in OS between the trial and the real-world populations was not statistically significant (unadjusted hazard ratio, 1.09 [95% confidence interval, 0.87-1.37]; P = 0.44).; Conclusion: Despite differences in patient characteristics, OS of patients treated in the control arm of OVHIPEC-1 was similar to patients treated outside the trial. The trial population accurately represents real-world patients with stage III EOC undergoing interval CRS in terms of outcome. (© 2022 International Federation of Gynecology and Obstetrics.)

Van Suijlichem, M., et al. (2021). "Recurrence and survival after laparoscopy versus laparotomy in earlystage endometrial cancer: long-term outcomes of a randomised trial." International Journal of Gynecological Cancer 31(SUPPL 4): A4.
	Objectives Laparoscopic hysterectomy is accepted globally as the standard treatment option for early‐stage endometrial cancer, but there is limited long‐term survival data. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH) for early‐stage endometrial cancer up to 5 years after each procedure. Methods Follow‐up of a multi‐centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Assessed at 5 years, the primary outcome was the disease‐free survival (DFS) and the secondary outcomes were the overall survival (OS), disease‐specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, and grade, with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. Results In total, 279 women underwent procedures and 263 (94%) of these had follow‐up data. For the TLH (n=185) and TAH (n=94) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.76; 95%CI, 0.35‐1.66), OS (89.2% vs 82.8%; aHR [death], 0.64; 95%CI, 0.33‐1.27), and DSS (95.0% vs 89.8%; aHR[death], 0.74; 95%CI, 0.28‐1.99) were comparable at 5 years. There were no port‐site or wound metastases, and local recurrence rates were comparable. Conclusions No study has reported on survival among women with early‐stage endometrial cancer treated by TLH or TAH without routine lymphadenectomy. Survival outcomes (DFS, OS and DSS) were comparable between the treatment options at 5 years, supporting the widespread use of TLH as a primary treatment for early‐stage, low‐grade endometrial cancer.

Van Tai, N., et al. (2021). "Dose-dense cisplatin-based neoadjuvant chemotherapy increases survival in advanced cervical cancer: a meta-analysis."
	Review question To demonstrate the benefit of using dose-dense cisplatin-based neoadjuvant chemotherapy for the treatment of locally-advanced cervical cancer in terms of overall survival Searches For the search strategy, we applied the following method: using an ad hoc algorithm composed of both thesaurus and free text terms, we searched MEDLINE via PubMed and Cochrane Library for articles published up to December, 2020. The algorithm was the following: (“Uterine Cervical Neoplasms” [MeSH] OR “Cervix Neoplasms” OR “Cervix Cancer” OR “Cervical Neoplasm”) AND (“Locally Advanced”) AND (“Neoadjuvant Therapy”[MeSH] OR “Neoadjuvant Chemotherapy”). In addition, the references contained in the articles and relevant reviews identified were also considered to avoid eligible articles being missed. Two authors (Van Tai Nguyen and Guilhem Bousquet) independently screened the papers retrieved, initially by titles, then by abstracts, and finally by full texts. In case of discordance, a third author (Frédéric Pamoukdjian) was solicited to make the decision whether or not to retrieve the paper. Types of study to be included Randomized clinical trials Condition or domain being studied Locally-advanced cervical cancer stages IB2 to IVA according to International Federation of Gynecology and Obstetrics (FIGO) Participants/population All patients had stages IB2 to IVA cervical cancer according to International Federation of Gynecology and Obstetrics (FIGO) Intervention(s), exposure(s) Locally-advanced cervical cancer patients received cisplatin-based neoadjuvant chemotherapy followed by chemoradiotherapy or radiotherapy or surgery Comparator(s)/control Locally-advanced cervical cancer patients patients did not receive neoadjuvant chemotherapy, local treatment such as chemoradiotherapy or radiotherapy alone or surgery alone Main outcome(s) Overall survival (OS) was defined as the time interval between the date of diagnosis and the date of death from any cause or the last follow-up. Measures of effect The pooled results were summarized as Risk-Ratios (RRs) and their 95% Confidence Interval (95%CI) in a forest plot using fixed or random effect as appropriate Additional outcome(s) Progression-free survival (PFS) was defined as the time interval between the date of diagnosis and the date of the first relapse at any site or death from any cause. Measures of effect The pooled results were summarized as Risk-Ratios (RRs) and their 95% Confidence Interval (95%CI) in a forest plot using fixed or random effect as appropriate Data extraction (selection and coding) For this first stage of the meta-analysis, we will extract from trial protocols, summary data on trial and patient characteristics and interventions. We will also seek the results (hazard ratio (HR) and associated statistics, number of events (deaths or relapsed)) for the outcome of overall survival or progression-free survival from articles. • Trial accrual period (min, max and median follow-up) • Summaries of patient characteristics at randomization: age (median/mean and range), tumour stage, treatment allocated, regimen of neoadjuvant chemotherapy, local treatment. • Events overall survival and progression-free survival Risk of bias (quality) assessment The quality of the randomized clinical trials was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI) guidelines (sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias), and the risk of bias was classified as low, unclear, or high. Strategy for data synthesis The primary analysis will combine the risk ratios across trials using the fixed-effect model to give pooled risk ratios that represent the overall risk of an event on cisplatin-based neoadjuvant chemotherapy followed by local treatment compared with local treatment alone in terms of overall survival and progression-free survival for the treatment of locally-advanced cervical cancer. We assessed the heterogeneity of study results by using the I² indicator and Cochran’s Q test. I² values of 0%, 25%, 50% and 75% were considered to indicate absence of heterogeneity, low, moderate and high heterogeneity respectively. A P value ≤ 0.05 on the Q-test indicated significant heterogeneity. Publication bias was assessed both graphically using a funnel plot and quantitatively with a linear regression test of funnel plot asymmetry (non-significant P value meaning no publication bias). All tests were two sided, and the threshold for statistical significance was set at a P-value of less than 0.05. Analysis of subgroups or subsets Analyses by neoadjuvant chemotherapy protocol: Trials in the meta-analysis differ by the planned use of cisplatin-based neoadjuvant chemotherapy, therefore we have planned an analysis in which trials are grouped according to use of neoadjuvant therapy: . Dose-dense cisplatin-based chemotherapy . Duration of neoadjuvant chemotherapy (≤ 6 weeks or > 6 weeks) . Triplet or doublet cisplatin-based chemotherapy A risk ratio will be calculated for each trial group and for all trials together, using the fixed-effect model to give pooled hazard ratios that represent the overall risk of an event on neoadjuvant chemotherapy followed by local treatment compared with local treatment alone in terms of overall survival. Contact details for further information Van Tai Nguyen nguyentai10241@gmail.com Organisational affiliation of the review Université de Paris-Université Sorbonne Paris Nord https://www.univ-paris13.fr Review team members and their organisational affiliations Dr Van Tai Nguyen. Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S942, Université de Paris-Université Sorbonne Paris Nord, 93000 Bobigny, France Dr Sabine Winterman. Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, Service d’Oncologie Médicale, 93000 Bobigny, France. Dr Margot Playe. Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, Service de Médecine Nucléaire, 93000 Bobigny, France. Dr Amélie Benbara. Assistance Publique Hôpitaux de Paris, Hôpital Jean Verdier, Service de Gynécologie – Obstétrique, 93140 Bondy, France Professor Laurent Zelek. Université Sorbonne Paris Nord, 9 Avenue Jean Baptiste Clément, 93439 Villetaneuse, France. Assistant/Associate Professor Frédéric Pamoukdjian. Assistance Publique Hôpitaux de Paris, Hôpital Avicenne, Service de Médecine Gériatrique, 93000 Bobigny, France Professor Guilhem Bousquet. Université Sorbonne Paris Nord, 9 Avenue Jean Baptiste Clément, 93439 Villetaneuse, France Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 01 December 2020 Anticipated completion date 27 April 2021 Funding sources/sponsors Institut National de la Santé et de la Recherche (INSERM), University of Paris Grant number(s) State the funder, grant or award number and the date of award Conflicts of interest Language English Country France Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Neoadjuvant Therapy; Uterine Cervical Neoplasms Date of registration in PROSPERO 28 April 2021 Date of first submission 29 March 2021 Stage of review at time of this submission

van Till, J. W. O., et al. (2022). "Muscarinic-3-receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial." Neurourology and Urodynamics 41(5): 1139-1148.
	Aim: The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3-PAM), in patients with underactive bladder (UAB). Method(s): A randomized, double-blind, placebo-controlled multicenter study was performed in adult male/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR] > 100 ml) without significant bladder outlet obstruction and/or overactive bladder. Subjects were randomized (1:1) to receive 4-week oral once-daily administration of 100 mg ASP8302 or matching placebo. Primary endpoint was a change from baseline in PVR measured by catheterization after standardized bladder filling (PVRC2). Other endpoints included PVR and bladder voiding efficiency (BVE) measured in various ways, uroflowmetry, bladder diary, and questionnaires. Pressure-flow studies were performed in a subgroup. Result(s): One hundred and thirty-five patients were randomized (ASP8302 group: 65 patients, placebo group: 70 patients). The median change in PVRC2 was -40.0 ml (ASP8302) versus -35.0 ml (placebo) and the difference between groups was -5.0 ml (p = 0.960). In males, functional and symptomatic outcomes improved, for example, maximum urine flow rate (Qmax) and detrusor pressure at Qmax (Pdet.Qmax) increased (mean difference in change ASP8302 vs. placebo: 3.8 ml/s, p = 0.031 and 12.7 cm H2O, p = 0.034, respectively). Urinary incontinence episodes/24 h decreased in males with preexisting incontinence (mean difference: -0.35; p = 0.028). The incidence of adverse events was similar between study groups (ASP8302: 33.3%, placebo: 31.4%). In the included subjects, both baseline urine flow and bladder voiding pressure was low. Compared with PVR, simultaneous BVE measurements were more consistent between various methods (spontaneous vs. standardized bladder filling, catheterization vs. ultrasound [US]). Conclusion(s): ASP8302 was safe and well tolerated in patients with UAB identified by nonurodynamic clinical criteria, but it did not show efficacy in the primary endpoint. However, in males it showed improvement of symptoms and functional parameters. BVE (using US) is a more optimal outcome measure than PVR in UAB.Copyright © 2022 Wiley Periodicals LLC.

van Triest, B., et al. (2021). "Phase II study of definitive chemoradiation for locally advanced squamous cell cancer of the vulva: An efficacy study." Gynecologic Oncology 163(1): 117-124.
	Objective: To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival.; Methods: In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated.; Results: 52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute ≥ grade 3 toxicities were regarding skin/mucosa and pain (54% and 37%). Late ≥grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years.; Conclusions: Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Van Uytsel, H., et al. (2023). "Effect of the INTER-ACT lifestyle intervention on maternal mental health during the first year after childbirth: A randomized controlled trial." PloS One 18(7 July): e0284770.
	We assess whether the INTER-ACT postpartum lifestyle intervention influences symptoms of depression and anxiety, sense of coherence and quality of life during the first year after childbirth. A total of 1047 women of the INTER-ACT RCT were randomized into the intervention (n = 542) or control arm (n = 505). The lifestyle intervention consisted of 4 face-to-face coaching sessions, supported by an e-health app. Anthropometric and mental health data were collected at baseline, end of intervention and 6-months follow-up. We applied mixed models to assess whether the evolution over time of depressive symptoms, anxiety, sense of coherence and quality of life differed between the intervention and control arm, taking into account the women's pre-pregnancy BMI. There was no statistical evidence for a difference in evolution in anxiety or quality of life between intervention and control arm. But an improvement in symptoms of depression and sense of coherence was observed in women who received the intervention, depending on the mother's pre-pregnancy BMI. Women with normal/overweight pre-pregnancy BMI, reported a decrease in EPDS between baseline and end of intervention, and the decrease was larger in the intervention arm (control arm: -0.42 (95% CI, -0.76 to -0.08); intervention arm: -0.71 (95% CI, -1.07 to -0.35)). Women with pre-pregnancy obesity showed an increase in EPDS between baseline and end of intervention, but the increase was less pronounced in the intervention arm (control arm: +0.71 (95% CI, -0.12 to 1.54); intervention arm: +0.42 (95% CI -0.42 to 1.25)). Women with a normal or obese pre-pregnancy BMI in the intervention arm showed a decrease in sense of coherence between baseline and end of intervention (-0.36) (95% CI, -1.60 to 0.88), while women with overweight pre-pregnancy showed an increase in sense of coherence (+1.53) (95% CI, -0.08 to 3.15) between baseline and end of intervention. Receiving the INTER-ACT postpartum lifestyle intervention showed improvement in depressive symptoms, in normal weight or overweight women on the short run, as well as improvement in sense of coherence in women with pre-pregnancy overweight only.Copyright © 2023 Van Uytsel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Van Vaerenbergh, I., et al. (2021). "Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients." Reproductive Biology and Endocrinology 19(1): 26.
	Background: Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. Method(s): A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22-39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. Result(s): The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or >= 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3-4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. Conclusion(s): This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. Trial registration: Clinicaltrials.gov, NCT03659786/NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.Copyright © 2021, The Author(s).

van Weelden Willem, J., et al. (2023). "The effect of progestin therapy in advanced and recurrent endometrial cancer: A systematic review and meta-analysis." BJOG : an international journal of obstetrics and gynaecology 130(2): 143-152.
	Background: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.; Objectives: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.; Search Strategy: We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.; Selection Criteria: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.; Data Collection and Analysis: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.; Main Results: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.; Conclusions: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear. (© 2022 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

van Weelden Willem, J., et al. (2019). "Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review." Frontiers in Oncology 9: 359.
	Introduction: Hormonal therapy in endometrial cancer (EC) is used for patients who wish to preserve fertility and for patients with advanced or recurrent disease in a palliative setting. First line hormonal therapy consists of treatment with progestins, which has a response rate of 25% in an unselected population. Treatment with anti-estrogens is an alternative hormonal therapy option, but there is limited data on the effect and side-effects of anti-estrogens in EC. Therefore, we performed a systematic review to investigate the response rate and toxicity of anti-estrogenic therapy in patients with endometrial cancer. Methods: A systematic search in electronic databases was performed to identify studies on selective estrogen receptor modulators (SERM) and down-regulators (SERD) and aromatase inhibitors that reported on response rates (RR) among EC patients. Outcome in estrogen receptor (ER) positive and negative disease was assessed independently. Results: Sixteen studies on advanced stage and recurrent EC were included. Ten studies investigated anti-estrogen monotherapy and seven investigated a combination of anti-estrogenic drugs with either progestin or targeted treatment. Due to heterogeneity in patient population, no meta-analysis was performed. The median age of the patients in the included studies ranged from 61 to 71 years and the proportion of low grade tumors ranged from 38 to 80%. The RR for tamoxifen ranged from 10 to 53%, for other SERMs and SERDs 9-31%, for aromatase inhibitors from 8 to 9%, for combined tamoxifen/progestin treatment 19-58%, for combined chemo- and hormonal therapy 43% and for combination of anti-estrogenic treatment with mammalian target of rapamycin (mTOR) inhibitors 14-31%. Toxicity consisted mainly of nausea and thrombotic events and was higher in combination therapy of chemotherapy and hormonal therapy and hormonal therapy and mTOR inhibitors compared to other therapies. Conclusion: Tamoxifen or a combination of tamoxifen and progestin should be the preferred choice when selecting second line hormonal treatment because the RRs are similar to first line progestin treatment and the toxicity is low. The response can be optimized by selecting patients with endometrioid tumors and positive estrogen receptor status, which should be based on a pretreatment biopsy.

van Wessel, S., et al. (2021). "Hysteroscopic morcellation versus bipolar resection for removal of type 0 and 1 submucous myomas: a randomized trial." European Journal of Obstetrics, Gynecology, and Reproductive Biology 259: 32‐37.
	Objectives: To compare hysteroscopic morcellation with bipolar resection for the removal of submucous type 0 and 1 myomas, in terms of procedure time (primary outcome), adverse events, tissue availability, short term effectiveness and postoperative adhesion formation (secondary outcomes). Study design: The study was performed from May 2011 to May 2018 in the Catharina hospital (Eindhoven, the Netherlands) and the Ghent University hospital (Ghent, Belgium). Women with type 0 and 1 submucous myomas up to 3 cm were randomized to hysteroscopic morcellation with the TruClearTM 8.0 Tissue Removal System or to bipolar resection with a rigid 8.5‐mm resectoscope. Skewed time variables were log‐transformed and analyzed with the Student t‐test. Multiple linear regression analysis was performed to assess the effect of myoma diameter on operating time. Results: Forty‐five and 38 women were included in the hysteroscopic morcellation and resection group, respectively. The median operating time was significantly shorter for hysteroscopic morcellation compared with resection (9.2 min [interquartile range 5.6–14.4] versus 13.4 min [interquartile range 8.6–17.5], P =.04). In the morcellation group, operating time, corrected for the myoma diameter, was reduced by 26 % (95 % CI 5–43%; P =.02). The median setup time was significantly longer in the morcellation group (5.2 min [interquartile range 4.2–6.9] versus 3.8 min [interquartile range 3.3–5.3], P =.006). The median total procedure time was not significantly different between the two techniques (14.4 min [interquartile range 11.4–19.2] versus 17.3 [interquartile range 12.7–23.8], P =.18). Two procedures of the morcellation group were converted to bipolar resection because of the myoma hardness. Complete resection was found in 89 % of the morcellation group and 95 % of the resection group. Adverse events occurred in 3 patients of the morcellation group, namely a fluid deficit > 2500 mL with the need of potassium suppletion, an asystolic vasovagal response after conversion to resection and postoperative fever requiring antibiotics. Tissue was available for pathology analysis in all cases. Routine second‐look hysteroscopy performed in one center showed no intrauterine adhesions. Conclusion: Overall, there is no difference in total procedure time between hysteroscopic morcellation using the TruClearTM system compared to bipolar resection for the removal of smaller type 0 and 1 submucous myomas. Although hysteroscopic morcellation is faster, its setup time is longer. Calcified myomas can be challenging and fluid deficit remains a limiting factor.

Vanessa Bergamin, B., et al. (2022). "Is parenteral morphine administration more efficient than oral morphine in reducing postoperative pain and side effects in patients undergoing hysterectomy?".
	Review question Is parenteral morphine administration more efficient than oral morphine in reducing postoperative pain and side effects in patients undergoing hysterectomy? Searches MEDLINE - September, 16th, 2022 Embase - September, 16th, 2022 Web of Science - September, 16th, 2022 Scopus - September, 16th, 2022 LILACS - September, 16th, 2022 No restrictions were used in the searches. Types of study to be included Randomized Clinical Trials Condition or domain being studied Patients after hysterectomy surgery may have acute or chronic post-surgical pain. These conditions can often be treated with morphine, in different routes of administration. Morphine can often be ineffective in controlling pain and even cause adverse effects such as nausea, vomiting, drowsiness. Oral administration of morphine requires high doses for pain control, in addition to adverse effects. Thus, the objective of this systematic review is to evaluate the effectiveness in the treatment of pain, as well as the adverse effects of parenteral administration of morphine, compared with oral administration, in hysterectomized patients with postoperative pain. Participants/population patients undergoing hysterectomy presenting post-surgical pain Intervention(s), exposure(s) Postoperative pain control is essential for the comprehensive care of the surgical patient, since prolonged painful stimuli seem to predispose to greater suffering and complications in the postoperative period. For pharmacological treatment, morphine is one of the drugs of choice. Analgesic prescriptions should often happen on a "if needed" schedule. Such a scheme provides the supply for episodes of pain peaks. The use of parenteral route for morphine administration is an alternative for postoperative pain control. Thus, this study evaluates, based on the rational use of drugs, whether the parenteral route is more efficient in controlling postoperative pain and systemic adverse effects. Comparator(s)/control The administration of oral morphine may not be effective in controlling postoperative pain and have many adverse effects. Inclusion criteria: studies with patients undergoing hysterectomy surgery, with post-surgical pain; studies describing morphine use and administration routes; studies that describe the effectiveness in the treatment of pain and adverse effects; and randomized clinical trials. Exclusion criteria: studies in children and adolescents; studies in patients with renal and hepatic failure Main outcome(s) The main outcome is the control of post-surgical pain in patients hysterectomized by oral or parenteral morphine. Pain is a frequent phenomenon in the postoperative period and can result in unnecessary suffering and risks for the patient. Additional outcome(s) The additional outcome is the frequency and intensity of systemic adverse effects, such as nausea, vomiting, somnolence and constipation. It is also relevant to evaluate tolerance and dependence. Our hypothesis is that parenteral morphine leads to lower frequency and intensity of adverse effects compared to oral morphine. Data extraction (selection and coding) After searches in MEDLINE, Web of Science, Scopus, Embase and LILACS and elimination of duplicate studies the investigators will read titles and abstracts of the identified and selected studies according the inclusion criteria. Next, the investigators will read the full text of the selected studies to verify which of them will be introduced in the research. Both steps will be performed by three researchers (R.A.L.S, R.F.R and V.B.B.M) in independently way, and the conflits will be resolved in a consensus reunion with other researchers (L.H.T and T.M.R). The inclusion criteria are: studies w with patients who underwent hysterectomy and present with postoperative pain; studies that describe use of morphine and routes of administration; studies that describe the effectiveness of pain treatment and adverse effects; and randomized clinical trials. The exclusion criteria are: studies with patients with liver and kidney failure, studies with pregnant patients, and studies with children and adolescents. The follow data will be collected from the studies : authors names, year, country of study, patients characteristics, information about surgery, level of pain, drug and administration route, adverse effects and effectiveness of the pain control. Risk of bias (quality) assessment To evaluate the risk of bias (quality), will be used the Cochrane's tool, the Cochrane risk-of-bias tool for randomized trials (RoB2), that is structured into a fixed set of domains of bias, including series of questions to elicit information about features of the trial that are relevant. Based on answers to the questions, that focus on different aspects of trial design, conduct and reporting, an algorithm will generate the proposed judgement about the risk of bias, that can be 'low' or “high” risk of bias or can express “some concerns”. Strategy for data synthesis To synthesize the data will be used the measure of effectiveness of pain control used in the studies. A meta-analysis will be perform considering pain level if the studies show low or moderate risk of bias e low heterogeneity. The heterogeneity's significance analyses will be realized by the x square test with significance level of 10%, while the heterogeneity's magnitude will be defined by the E. It will be considered acceptable an I.I< 50%. The concordance between the researchers in the selection phase will be analyzed by the kappa coefficient by Cohen. Analysis of subgroups or subsets The variables of interest used in data extraction will be specific to each study design. Contact details for further information VANESSA BERGAMIN BORALLI MARQUES vanessa.marques@unifal-mg.edu.br Organisational affiliation of the review UNIFAL-MG www.unifal-mg.edu.br Review team members and their organisational affiliations Professor VANESSA BERGAMIN BORALLI MARQUES. UNIFAL-MG Professor Larissa Helena Lobo Torres Pcheco. UNIFAL-MG Professor Tiago Marques dos Reis. UNIFAL-MG Miss Rafaela Figueiredo Rodrigues. UNIFAL-MG Rafael Alves Laudares Silva. UNIFAL-MG Dr Carlos Marcelo de Barros. UNIFAL-MG Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 02 September 2022 Anticipated completion date 16 December 2022 Funding sources/sponsors not applicable Grant number(s) State the funder, grant or award number and the date of award not applicable Conflicts of interest Language English Country Brazil Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Analgesia, Patient-Controlled; Female; Humans; Hysterectomy; Morphine; Pain, Postoperative Date of registration in PROSPERO 29 September 2022 Date of first submission 18 September 2022 Stage of review at time of this submission

Vania, C., et al. (2022). "Homologous Recombination Deficiency Testing in Patients with High-Grade Serous or Endometrioid Epithelial Ovarian Cancer: A Health Technology Assessment."
	Review question Clinical Review In patients with platinum-sensitive, high-grade, serous or endometrioid epithelial ovarian cancer: 1. What are the effectiveness and safety of niraparib (monotherapy) maintenance therapy compared with no maintenance therapy in patients with homologous recombination deficiency (HRD) and patients with homologous recombination proficiency? 2. What is the clinical utility of HRD testing compared with no HRD testing to inform discussions regarding the use of niraparib (monotherapy) maintenance therapy? Quantitative Preferences Review For patients with ovarian, fallopian tube, and peritoneal cancer: 1. What are the quantitative patient and health care provider preferences for HRD testing to inform discussions on maintenance therapy with poly-ADP-ribose polymerase (PARP) inhibitors? 2. How does HRD testing impact patients’ decisional conflict with regards to maintenance therapy with PARP inhibitors and psychological well-being? 3. What are the quantitative patient and health care provider preferences for maintenance therapy with PARP inhibitors? Economic Review In patients with platinum-sensitive, high-grade, serous or endometrioid epithelial ovarian cancer: 1. What is the cost-effectiveness of HRD testing for guiding niraparib maintenance therapy decision compared with usual care without HRD testing? In addition to the questions described above, this health technology assessment will evaluate the budget impact of HRD testing for people with high-grade serous or endometrioid epithelial ovarian cancer, as well as the experiences, preferences, and values of people with ovarian cancer. Searches We will perform a literature search using the Ovid interface to search the following databases: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Health Technology Assessment, and National Health Service Economic Evaluation Database (NHSEED), We will search the literature from inception to the current date and the results will be limited to English language publications. The final search strategy will be peer reviewed. Database auto-alerts will be created in MEDLINE and Embase, and monitored for the duration of the review. We will also perform a targeted grey literature search of Health Technology Assessment database and agency sites, clinical trial and systematic review registries. In addition, a literature search for quantitative preferences evidence will be based on the clinical review search strategy. We will perform a literature search using the Ovid interface to search MEDLINE and the EBSCOhost interface to search the Cumulative Index to Nursing & Allied Health Literature (CINAHL). A filter for preferences and values developed by Selva et al will be applied. Finally, an economic literature search will be performed using the clinical search strategy with an economic filter applied. Search results will be limited to English language publications. The final search strategy will be peer reviewed. Database auto-alerts will be created in MEDLINE, Embase, and CINAHL and monitored for the duration of the review. Types of study to be included Clinical and Quantitative Preferences Reviews Inclusion Criteria • English-language full-text publications • Studies published from inception and the day of the search • Randomized controlled trials, comparative observational studies, health technology assessments, and systematic reviews (Clinical Review) • Studies on patient and health care provider preferences for HRD testing that use quantitative measures (Quantitative Preferences Review) Exclusion Criteria • Non-comparative observational studies, qualitative studies, editorials, commentaries, case reports, conferences abstracts, letters • Animal and in vitro studies Economic Review Inclusion Criteria • English-language full-text publications • Studies comparing HRD testing guided niraparib maintenance therapy with usual care without HRD testing for maintenance therapy • Cost-utility, cost-effectiveness, cost-benefit, cost-consequence, or cost analyses Exclusion Criteria • Narrative reviews, letters/editorials, case reports, commentaries, abstracts, posters, unpublished studies Condition or domain being studied Epithelial is the most common type of malignant ovarian cancer (approximately 90% of ovarian cancer cases) and serous carcinoma is the most common form of epithelial ovarian cancer (approximately 75%). Ovarian cancer is classified as stages I through IV. Serous and endometrioid ovarian cancer can be classified as high- or low-grade. Primary treatment for advanced HGSOC and grade 2/3 endometrioid epithelial ovarian cancer generally consists of cytoreductive surgery followed by systemic chemotherapy with platinum-based regimens. Patients with a complete/partial response to platinum-based chemotherapy may be candidates for maintenance therapy--poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors such as niraparib are options for maintenance therapy. Homologous recombination repair (HRR) is the key pathway that enables error-free repair of double-strand DNA breaks—damage or dysregulation of key pathway genes leads to homologous recombination deficiency (HRD). Cells harbouring HRD are unable to reliably repair DNA double-strand breaks, leading to genomic instability. Studies suggest that patients with ovarian cancer and HRD may demonstrate a superior response to PARP inhibitors. Different types of tests can assess HRD status such as tests that identify specific HRR pathway–related gene variants (BRCA1/2 and other genes), genomic scar and mutational signature tests, and functional tests. Participants/population Clinical and Economic Review Inclusion Criterion: • Patients with high-grade serous ovarian, fallopian tube, or peritoneal cancer, or endometrioid epithelial ovarian cancer who are sensitive to platinum-based chemotherapy, newly diagnosed or relapsed, and who are candidates for niraparib monotherapy maintenance therapy Exclusion Criterion: • Patients with ovarian or other cancers who are candidates for maintenance therapy with other PARP inhibitors or other drugs Quantitative Preferences Review Inclusion Criterion: • Patients with ovarian, fallopian tube, and peritoneal cancer, newly diagnosed or relapsed, and their health care providers Exclusion Criterion: • Patients with other cancers Intervention(s), exposure(s) Clinical Review (Question 1) and Economic Review Inclusion Criterion: • Maintenance therapy with niraparib as monotherapy based on studies in which HRD status was measured Exclusion Criteria: • Maintenance therapy with other PARP inhibitors or other drugs or chemotherapy with any drug • Studies in which HRD testing was not performed or in which BRCA testing alone was performed Clinical Review (Question 2) Inclusion Criterion: • HRD testing used in studies that evaluated the clinical outcomes of maintenance therapy with niraparib as monotherapy Exclusion Criteria: • HRD testing used in studies that evaluated maintenance therapy with other drugs or any chemotherapy • Studies in which HRD testing was not performed or in which BRCA testing alone was performed Quantitative Preferences Review Questions 1 and 2 Inclusion Criterion: • HRD testing used in studies on maintenance therapy with PARP inhibitors Exclusion Criteria: • HRD testing in studies that evaluated maintenance therapy with other drugs or chemotherapy • Studies in which BRCA gene testing alone was performed Question 3 Inclusion Criterion: • Maintenance therapy with PARP inhibitors Exclusion Criterion: • Maintenance therapy with other drugs or any chemotherapy Comparator(s)/control Clinical Review Question 1 Inclusion Criteria: • No maintenance therapy based on studies in which HRD status was measured Exclusion Criteria: • Any maintenance therapy or any chemotherapy • Studies in which BRCA testing alone was performed Question 2 Inclusion Criteria: • No HRD testing performed. Based on studies that evaluated the clinical outcomes of maintenance therapy with niraparib as monotherapy Exclusion Criteria: • Studies in which HRD testing was performed, including BRCA testing alone • Studies assessing maintenance therapy with other drugs Quantitative Preferences Review Inclusion Criteria: • No HRD testing or • No comparator Exclusion Criterion: • Studies in which HRD testing was performed, including BRCA gene testing alone Economic Review Inclusion Criterion: • Usual care without HRD testing for maintenance therapy Exclusion Criteria: • Any maintenance therapy or any chemotherapy • Studies in which BRCA testing alone was performed Context Setting and Timing: Any Main outcome(s) Clinical Review • Progression-free survival (questions 1 and 2) • Overall survival (questions 1 and 2) • Chemotherapy-free interval and time to subsequent treatment (questions 1 and 2) • Quality of life and functional assessment, generic and disease-specific (questions 1 and 2) • Safety, treatment and testing adverse events (questions 1 and 2) • Treatment discontinuation (questions 1 and 2) • Use of HRD testing to inform maintenance therapy decisions (question 2) Quantitative Preferences Review • Patient and health care provider preferences for HRD testing • Patient and health care provider preferences for the use of HRD testing to inform decisions for maintenance therapy with PARP inhibitors • Decisional conflict of patients to undergo HRD testing and maintenance therapy with PARP inhibitors • Psychological effects (e.g., anxiety, distress, worry) of HRD testing Economic Review • Costs • Health outcomes (e.g., progression free survival, survival, quality-adjusted life years) • Incremental costs • Incremental effectiveness • Incremental cost-effectiveness ratios Measures of effect The measures of effect for categorical outcomes (progression-free and overall survival and for frequencies of adverse events) will be the hazard ratio, risk difference, or risk ratio, depending on how the information is provided in the studies. The measure of effect for continuous outcomes (quality of life) will be the mean difference. Additional outcome(s) None Measures of effect None Data extraction (selection and coding) Clinical Review Two reviewers will follow the Cochrane rapid review methods to screen titles and abstracts using Covidence systematic review management software, and obtain the full text of studies that appear eligible for the review, according to the inclusion criteria. One reviewer will then examine the full-text articles and select studies that meet the inclusion criteria. A second reviewer will screen all excluded full-text articles. Any disagreements between reviewers during screening will be resolved by consensus. Reference lists of included studies will also be examined by one reviewer for any additional relevant studies not identified through the search. Citation flow and reasons for exclusion for full-text articles will be reported according to the PRISMA statement. One reviewer will extract relevant data on study design and characteristics, risk-of-bias items, results, and PICOTS (population, intervention, comparator, outcome, time, and setting). Data extraction accuracy will be validated by a second reviewer. We will contact authors of the studies to provide clarification as needed. Quantitative Preferences Review One reviewer will use Covidence software to conduct an initial screen of titles and abstracts, and obtain the full text of studies that appear eligible for the review, according to the inclusion criteria. The reviewer will then examine the full text articles and select studies that meet the inclusion criteria. Reference lists will also be examined for additional studies not identified through the search. Citation flow and reasons for exclusion for full text articles will be reported according to the PRISMA statement. Economic Review We will extract the following information from included studies, such as the first author, country, year of publication, population, perspective, time horizon and outcomes (e.g., health outcomes, costs, incremental cost-effectiveness ratios). Study selection and data abstraction will be completed by one reviewer and validated by a second reviewer. Risk of bias (quality) assessment Clinical Review One reviewer will assess risk of bias using the Cochrane risk of bias tool for RCTs and for non-randomized studies, and the Risk of Bias in Systematic Reviews (ROBIS) tool will be used for systematic reviews. We will evaluate the quality of the body of evidence for each outcome according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Handbook. A second reviewer will undertake verification of all judgments (and support statements). Quantitative Preferences Review We will not critically appraise the quality of the quantitative evidence on preferences and values. Economic Review A summary of the number of studies judged to be directly applicable, partially applicable, or not applicable to the research question will be presented. We may assess the methodological quality of the included studies, and the studies will be categorized as having minor limitations, potentially serious limitations, or very serious limitations. Strategy for data synthesis Clinical Review One reviewer will assess for the presence and extent of statistical heterogeneity and consider this when interpreting the results. We will undertake meta-analysis using the R package, if appropriate. A narrative summary of results will be provided if meta-analysis is not appropriate. Quantitative Preferences Review One reviewer will undertake a narrative summary of the results. Economic Review One reviewer will undertake a narrative summary of the results. Cost-Effectiveness Strategy If appropriate, we may develop a model to assess the cost-effectiveness of HRD testing guided niraparib maintenance therapy compared with usual care without HRD testing guided niraparib maintenance therapy in patients with high-grade serous ovarian, fallopian tube, or peritoneal cancer, or endometrioid epithelial ovarian cancer who are sensitive to platinum-based chemotherapy, newly diagnosed or relapsed, and who are candidates for niraparib maintenance therapy. The main clinical inputs will be based on a systematic review of the clinical evidence and costs will be derived from local sources. Where appropriate, an annual discount rate of 1.5% will be applied to both costs and health outcomes. We will estimate the incremental cost-effectiveness ratio and will examine uncertainty around this estimate. Budget Impact Analysis Strategy A budget impact analysis will estimate the cost burden of publicly funding HRD for the patients with high-grade serous ovarian, fallopian tube, or peritoneal cancer, or endometrioid epithelial ovarian cancer, newly diagnosed or relapsed, over the next 5 years. The analysis will be conducted from the perspective of the Ontario Ministry of Health. All costs will be reported in 2022 Canadian dollars. Analysis of subgroups or subsets Outcomes will be subgrouped according to HRD and BRCA1/2 mutation status. Additionally, we will report results subgrouped by any relevant PROGRESS-Plus factors if the information is provided in the studies. Contact details for further information Nancy Sikich RN MSc, Director, Health Technology Assessment, Quality Ontario (Quality)

Vannya, D., et al. (2023). "Polycystic ovarian syndrome therapy with modification of gut microbiota dysbiosis.A systematic review and meta-analysis of randomized controlled trials."
	Review question Does polycystic ovarian syndrome therapy based on modification of gut microbiota therapy improve gut microbiota, three main feature of polycystic ovarian syndrome, hormonal profile, metabolic markers, inflammation markers and infertility problems in women with polycystic ovarian syndrome? Searches We will conduct a systematic literature search in electronic database (PubMed, Scopus, EBSCO) from January 2012 until December 2022, without date restriction. The key search terms will include: polycystic ovarian syndrome AND therapy AND gut microbiota AND dysbiosis This review on English language only with no restrictions for geographic location and only in article that published will be applied. In addition, the reference lists of all identified articles will be examined to identify studies not captured by electronic searches. Types of study to be included Randomized controlled trials Condition or domain being studied Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with infertility problems. Excess of androgens, an/oligoovulation and polycystic ovarium morphology are the typical clinical features in women with PCOS. Recent evidence showed that PCOS is characterised by metabolic disorder, defective antioxidant balance and elevated inflammatory status, which play a role in the pathogenesis of the condition. It has been hypothesised that the gut microbiota dysbiosis is involved in the pathogenesis of PCOS in this past decade. Participants/population Women with PCOS receiving therapy with modification of gut microbiota dysbiosis. Intervention(s), exposure(s) Every therapy that have purpose to modify gut microbiota dysbiosis that can confer a health benefit on the host. The present review will aim to investigate the impact of every therapy on gut microbiota dysbiosis, three main feature of polycystic ovarian syndrome, hormonal profile, metabolic markers, inflammation markers and infertility problems in women with PCOS. Comparator(s)/control Women with PCOS not receiving therapy with modification of gut microbiota dysbiosis. Main outcome(s) Changes in gut microbiota dysbiosis will be considered as the primary outcomes. Three features of polycystic ovarian syndrome, hormonal profiles, metabolic markers, inflammation markers and infertility outcome changes will be considered as the secondary outcomes. Gut microbiota changes include alpha and beta diversity. Three features of polycystic ovarian syndrome include: an/oligoovulation, biochemistry and clinical hyperandrogenism and polycystic ovarian morphology. Hormonal profile will include: serum hormone binding globulin, luteinizing hormone, follicle stimulating hormone Metabolic profile will include: low density lipoproteins, very low density lipoproteins, high density lipoproteins, total cholesterol, triglycerids, fasting glucose, homeostatic model assessment of insulin resistance, body mass index, abdominal circumference, zonulin, short chain fatty acids. Biomarkers of inflammation and oxidative stress will include: Serum high sensitivity C-reactive protein, total glutathione, malondialdehyde, tumor necrosis factor alpha, interleukin 6, interleukin 10. Additional outcome(s) none Measures of effect none Data extraction (selection and coding) Three Authors (VD, ESL, NP), independently, will screen titles and abstracts and will assess the studies for inclusion. The same Authors independently will extract data about study features (country and time of realization of the study), included populations (participants number and main inclusion criteria), type of intervention (drugs and dosage) and study outcomes. The results will be compared, and any disagreement will be discussed and resolved by consensus. Risk of bias (quality) assessment The risk of bias in each included study will be assessed independently by three Authors (VD, ESL, NP) using the criteria outlined in the United State Preventive Services Task Force including 14 criteria. Review authors’ judgments will be categorized as good, fair, or poor when 0, 1, or ≥ 2 criteria defined as “fatal flaws” (randomization, dropout <20%, intention-to-treat analysis) were not fulfilled. Strategy for data synthesis Data analysis will be performed by one Author (VD) using Review Manager Version 5.3 Continuous variables will be compared by using the means and standard deviations of outcome measures and expressed as mean differences (MD) among Groups (95% CI). Dichotomous variables will be analysed using the risk ratio (RR) with a 95% confidence interval (95% CI). Significance level will be set at P was <0.05. Heterogeneity will be measured using I² (Higgins I²). The random effect model will be employed for data analysis. Analysis of subgroups or subsets none Contact details for further information Vannya Dewi vannyadp@gmail.com Organisational affiliation of the review Diponegoro University https://www.undip.ac.id Review team members and their organisational affiliations Ms Vannya Dewi. Diponegoro University Dr Endang Sri Lestari. Diponegoro University Professor Noor Pramono. Diponegoro University Type and method of review Intervention, Systematic review Anticipated or actual start date 20 February 2023 Anticipated completion date 03 April 2023 Funding sources/sponsors none Grant number(s) State the funder, grant or award number and the date of award none Conflicts of interest Language English Country Indonesia Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Infertility; Inflammation; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic Date of registration in PROSPERO 01 March 2023 Date of first submission 18 February 2023 Stage of review at time of this submission The review has not started

Varano, S., et al. (2022). "Efficacy and safety of Vibegron for the treatment of overactive bladder in women: A subgroup analysis from the EMPOWUR trial." International Urogynecology Journal 33(Supplement 1): S62-S63.
	Introduction: Overactive bladder (OAB) prevalence increases with age in women and men; however, women may be disproportionately affected by symptoms such as urge urinary incontinence (UUI). In the 12-week phase 3 EMPOWUR trial, vibegron was shown to be safe and efficacious in adults with OAB. Objective(s): These subgroup analyses of the EMPOWURtrial assessed the efficacy (prespecified) and safety (post hoc) of vibegron in treating women with OAB. Method(s): In EMPOWUR, patients were randomly assigned 5:5:4 to once-daily vibegron 75 mg, placebo, or tolterodine 4 mg ER, respectively. Efficacy endpoints were change from baseline at week 12 in mean daily number of micturitions and UUI episodes (co-primary) and urgency episodes (key secondary). Safety was assessed through adverse events (AEs), clinical laboratory assessments, and postvoid residual (PVR) urine volume. Result(s): Of the 1515 patients included in the safety set, 1286 (84.9%) were women (vibegron, N=463; placebo, N=459; tolterodine, N=364). Mean age was 59.5 years; 78.9% were white; and 18.7% were of childbearing potential. Among women, vibegron was associated with statistically significantly greater reductions (95% CI does not include 0) from baseline at week 12 vs placebo in average daily number of micturitions (least squares mean, -1.9 vs -1.4, respectively), UUI episodes (-2.1 vs - 1.4), and urgency episodes (-2.8 vs -1.9; Table 1). Incidence of treatment-emergent AEs (TEAEs) was 39.3% with vibegron, 34.9% with placebo, and 39.6% with tolterodine; 1.5%, 1.1%, and 3.8% of women, respectively, discontinued due to TEAEs (Table 2). Treatment-related TEAEs were reported by 13.4%, 11.1%, and 15.7% of women receiving vibegron, placebo, and tolterodine, respectively. The most common TEAE with vibegron reported at a higher rate than placebo was headache (Table 2). No clinically meaningful changes were seen in clinical laboratory parameters or in PVR urine volume. Conclusion(s): In women with OAB, once-daily vibegron was associated with significant reductions in key efficacy endpoints and a slightly higher rate of certain AEs vs placebo, consistent with results from EMPOWUR. Results suggest that vibegron is safe and efficacious in treating women with OAB.

Vargas, M., et al. (2024). "Adverse outcomes related to morcellation in Total Laparoscopic Hysterectomy." European Journal of Obstetrics and Gynecology and Reproductive Biology 294: 231-237.
	Objective: This study aimed to comprehensively evaluate the complications associated with morcellation in Total Laparoscopic Hysterectomy (TLH) procedures, providing evidence-based insights to enhance patient safety and surgical efficacy. Data sources: A comprehensive literature search was conducted using multiple databases, including PubMed, EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials. The inclusion criteria were Studies that focused on morcellation and morcellation-related complications were included. The risk of bias in the included studies was assessed using established evaluation scales. Methods of study selection: Thirteen studies investigating complications associated with morcellation in TLH (Total Laparoscopic Hysterectomy) were included in this review.This review covers intraoperative blood loss, length of hospital stay, loss of bag integrity, mean uterine specimen and weight, morcellation time, operation time, and TLH morcellation complications. Tabulation, integration, and results: The selected studies covered different approaches and aspects related to this procedure, providing valuable insights into the factors associated with complications and efficacy of the technique in various clinical settings.This review highlights the importance of evaluating and considering complications associated with morcellation in TLH. Conclusion(s): The findings of this review provide valuable insights into complications associated with morcellation in TLH. Clinicians could use this information to make informed decisions, implement safe protocols, and improve patient care. Addressing these complications will enhance the safety and efficacy of morcellation for TLH. Ethical Compliance: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.Copyright © 2024 Elsevier B.V.

Vargas, M., et al. (2022). "Cost-effectiveness Analysis of Early Sling Loosening Versus Delayed Sling Lysis in the Management of Voiding Dysfunction after Midurethral Sling Placement." Female Pelvic Medicine and Reconstructive Surgery 28(3): E103-E107.
	Objective The aim of this study was to perform a cost-effectiveness analysis comparing the management for ongoing voiding dysfunction after midurethral sling placement, including early sling loosening and delayed sling lysis. Methods A Markov model was created to compare the cost-effectiveness of early sling loosening (2 weeks) versus delayed sling lysis (6 weeks) for the management of persisting voiding dysfunction/retention after midurethral sling placement. A literature review provided rates of resolution of voiding dysfunction with conservative management, complications, recurrent stress urinary incontinence, or ongoing retention, as well as quality-adjusted life years (QALYs). Costs were based on 2020 Medicare reimbursement rates. Incremental cost-effectiveness ratios were compared using a willingness-to-pay threshold of $100,000/QALY. One-way and probabilistic sensitivity analyses were performed. Results At 1 year, early sling loosening resulted in increased costs ($3,575 vs $1,836) and higher QALYs (0.948 vs 0.925) compared with delayed sling lysis. This translated to early sling loosening being the most cost-effective strategy, with an incremental cost-effectiveness ratio of $74,382/QALY. The model was sensitive to multiple variables on our 1-way sensitivity analysis. For example, delayed sling lysis became cost-effective if the rate of voiding dysfunction resolution with conservative management was greater than or equal to 57% or recurrent stress urinary incontinence after early loosening was greater than or equal to 9.6%. At a willingness-to-pay threshold of 100,000/QALY, early sling loosening was cost-effective in 82% of microsimulations in probabilistic sensitivity analysis. Conclusions Early sling loosening represents a more cost-effective management method in resolving ongoing voiding dysfunction after sling placement. These findings may favor early clinical management in patients with voiding dysfunction after midurethral sling placement.Copyright © American Urogynecologic Society. All rights reserved.

Vargas-Maldonado, D., et al. (2021). "Cost-effectiveness analysis of early sling loosening versus delayed sling lysis in the management of voiding dysfunction after midurethral sling placement." Female Pelvic Medicine and Reconstructive Surgery 27(10 SUPPL 1): S34-S35.
	Objective: Synthetic midurethral slings are the most commonly utilized treatment for female stress urinary incontinence. Complications such as postoperative voiding dysfunction or urinary retention are encountered after 1-4% of sling placements. The management of this complication is heterogeneous, with some advocating for early sling loosening, as compared to delayed sling lysis for those with persistent voiding issues. These treatment strategies come with tradeoffs in regards to complications, potentially unnecessary intervention, and long-term quality of life. Direct comparative literature for these two management strategies is sparse. To compare these disparate management options, we sought to performa cost-effectiveness analysis for early sling loosening versus delayed sling lysis for voiding dysfunction after midurethral sling placement. Method(s): AMarkov analytic model was created to compare the cost-effectiveness of early sling loosening (2 week) versus delayed sling lysis (6 week) for the management of persisting voiding dysfunction/retention after midurethral sling placement. The model included resolution rates of voiding dysfunction over time with conservative management, short-term complications, as well as the rate of recurrent stress urinary incontinence, or ongoing retention. Probabilities and utility values were obtained from the literature and costs were based on 2020 Medicare reimbursement rates. Univariable sensitivity analyses were performed. Incremental cost-effectiveness ratios (ICER) were compared using awillingness to pay (WTP) threshold of $100,000/quality-adjusted life year (QALY). Result(s): At one year follow-up, early sling loosening resulted in increased costs ($3,575 vs $1,836) and higher quality-adjusted life years (0.948 vs 0.925) compared to delayed sling lysis. With an ICER of $74,381/QALY, early sling loosening was the most cost-effective strategy. The model was sensitive to multiple variables on one-way sensitivity analysis. For example, delayed sling lysis became cost-effective if the rate of retention resolution was >=57%, recurrent SUI after loosening >=9.6%, the utility value associated with severe SUI increased to greater than 0.78, or the cost of sling lysis was <= $1,974. Conclusion(s): Early sling loosening represents a more cost-effective management method in resolving ongoing voiding dysfunction after sling placement. However, this is dependent uponmultiple factors. These findings may favor early clinicalmanagement in patients with voiding dysfunction after midurethral sling placement.

Vargiu, V., et al. (2021). "Hormone replacement therapy and cervical cancer: a systematic review of the literature." Climacteric : the journal of the International Menopause Society 24(2): 120-127.
	Gynecological tumor treatment, including cervical cancer (CC) treatment, often leads to iatrogenic premature menopause. This highlights the critical importance of investigating indications for hormone replacement therapy (HRT), as most patients, thanks to the improvement in diagnosis and treatment, have to deal with the sequelae of their cancer treatments for many years. This systematic review aims to provide an overview of the current knowledge regarding the risks of HRT and CC. In particular, we aim to investigate whether the use of HRT can increase CC incidence, and evaluate its risk in CC survivors. A systematic review, in agreement with PRISMA guidelines, of the English literature present in PubMed and SCOPUS has been performed. A total of 2805 articles have been screened, of which 10 were considered eligible. Several studies reported a significantly reduced risk of developing cervical squamous cell carcinoma in postmenopausal women treated with HRT, while a weak increase in the incidence of adenocarcinoma has been shown. No evidence reports a harmful effect of HRT on CC oncological outcome, while several benefits, in terms of reduced metabolic risk and increased quality of life, have been described, thus concluding that HRT should be offered to young CC survivors for the management of early menopause.

Varikasuvu Seshadri, R., et al. (2022). "Effect of metformin intervention on circulating irisin levels in polycystic ovary syndrome: a systematic review and collaborative meta-analysis." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(3): 207-212.
	Background: Irisin is an adipo-myokine with potential implications in metabolic disorders such as polycystic ovary syndrome (PCOS). Despite of a strong evidence showing increased irisin level in PCOS, there is no conclusive evidence on the effect of metformin intervention on circulatory irisin in PCOS.; Aim: The aim of this meta-analysis was to compare the circulatory (serum/plasma) irisin levels before and after metformin intervention in subjects with PCOS.; Methods: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. A one-study leave-out sensitivity analysis was conducted to validate the overall obtained results.; Results: A total of five observations were included in this meta-analysis. The results based on random effects meta-analysis indicated that irisin levels were significantly decreased after metformin intervention as compared to the baseline pretreatment levels in PCOS (SMD: -1.00, 95% CI: -1.60 to -0.41, Z: 3.29, p = .001). The sensitivity analysis leaving-out a particular observation at a time and repeating the meta-analysis validated the robustness of the overall finding suggesting the significant effect of metformin treatment on irisin levels in PCOS.; Conclusion: Circulating irisin levels were significantly decreased upon metformin intervention in PCOS patients. The higher pretreatment irisin levels in PCOS may recede once the altered metabolic state is restored upon metformin intervention. Well-designed randomized trials with large sample sizes are warranted to further substantiate the reported evidence reported and to establish the possible mechanisms.

Varlas, V., et al. (2021). "Hysterolaparoscopy: A Gold Standard for Diagnosing and Treating Infertility and Benign Uterine Pathology." Journal of Clinical Medicine 10(16).
	BACKGROUND: Combined hysteroscopy and laparoscopy is a valuable method for diagnosing and treating infertility and benign uterine pathology. Both procedures are minimally invasive, reliable, and safe, with a low complication rate. AIM: In this review, we expose the efficiency and safety of hysterolaparoscopy in the management of infertility and other benign uterine pathologies. METHOD: We performed a systematic literature review on several databases: PubMed®/MEDLINE, PMC, Crossref.org, and Web of Science in the last 10 years. INCLUSION CRITERIA: Women of reproductive age with primary or secondary infertility and/or benign uterine pathology. EXCLUSION CRITERIA: pre-puberty, menopause, couple with male infertility. CONCLUSION: Hysterolaparoscopy is a useful tool to assess infertility and simultaneously diagnose and treat pelvic and uterine lesions.

Vasillios, P. and L. Efstathia (2021). "Survival outcomes of epithelial ovarian cancer patients following dose-dense vs 3-weekly platinum-paclitaxel chemotherapy: a meta-analysis."
	Review question The purpose of this meta-analysis is to evaluate differences on survival outcomes of epithelial ovarian cancer patients that undergo dose-dense chemotherapy based on platinum and paclitaxel to those of patients that undergo standard 3-weekly therapy with the same regimens. The prevalence and severity of side effects among the two groups (dose-dense and 3-weekly) will be investigated as well. Searches We will search MEDLINE (1966–2021), Scopus (2004–2021), ClinicalTrials.gov (2008–2021), Cochrane Central Register of Controlled Trials CENTRAL (1999-2021) and Google Scholar (2004-2021) from inception until October 2021 for relevant articles published in languages of Latin alphabet. dose-dense; three-weekly; 3-weekly; ovarian cancer; survival Types of study to be included Randomized controlled trials, observational studies (prospective and retrospective cohorts). Retrospective case control studies and retrospective case series will be excluded. Condition or domain being studied Epithelial ovarian cancer is the 8th most common cancer in women and the 5th leading cause of cancer-related deaths with an estimated annual prevalence of approximately 20, 000 new cases and 13, 000 deaths in the U.S. Chemotherapy is the cornerstone of adjuvant therapy in ovarian cancer. Standard chemotherapy is delivered with a platinum compound and a taxane one (mainly paclitaxel). Dose-dense schemes using the same compounds have been investigated and seem to be superior; however, they are accompanied by increased side effects. Outcomes: overall survival, progression free survival, observed toxicity Participants/population Inclusion criteria: Patients with epithelial ovarian cancer that undergo chemotherapy for primary disease (not for relapsing disease) with a scheme that includes a platinum compound and paclitaxel. Exclusion criteria: Patients with relapsing disease; patients that undergo chemotherapy with other drugs. Intervention(s), exposure(s) Epithelial ovarian cancer patients that undergo weekly chemotherapy with a platinum based compound and/or paclitaxel. Comparator(s)/control Epithelial ovarian cancer patients that undergo standard 3-weekly chemotherapy with a platinum based compound and paclitaxel. Main outcome(s) Overall survival rates; progression free survival rates; 3 and 5 year survival rates (overall and progression free); mean differences in survival rates in months Measures of effect Odds ratios and mean differences Additional outcome(s) Chemotherapy toxicity (gastrointestinal, cardiac, neurologic, infectious and nephrotoxicity). Measures of effect Odds ratios Data extraction (selection and coding) Study selection The titles and abstracts of all electronic articles will be screened to evaluate their eligibility. All articles that are presumed to meet the criteria will be retrieved as full texts. Screening and eligibility assessment will be performed independently by two reviewers (E.L and V.P.). Rayyan web app will be used for the screening process. Any disagreements between reviewers will be resolved by a third reviewer (M.L.). Data extraction Data extraction will be based on a modified data form that is based in Cochrane`s data collection form for intervention reviews for RCTs and non-RCTs and will include at least the year of publication of each study, country of origin, study design, number of patients in each group, outcomes (primary and secondary as described above). Two review authors (E.L and V.P.) will extract the data from included studies and a third author (M.L.) will check the extracted data. Extracted data will be recorded in an excel spreadsheet. In case of studies based on the same population, the most recent or the most complete publication will be used accordingly. Any disagreements will be resolved by discussion and consensus between the authors. Risk of bias (quality) assessment [1 change] The methodological quality of included randomized controlled trials will be assessed at study level by two independent reviewers using the risk of bias 2 (RoB 2) tool. RoB2 incorporates five domains that include assessment of i) risk of bias that arises from the randomization process, ii) risk of bias due to deviations from the intended interventions, iii) missing outcome data, iv) risk of bias in the measurement of the outcome, and v) risk of bias in the selection of the reported result. The quality of non-randomized trials will be assessed with Risk of Bias in non-Randomized Trials (ROBINS-I) tool which incorporates domains that investigate bias that arises from i) confounders, ii) selection of participants, iii) selective reporting in intervention measures, iv) deviations from intended intereventions , v) missing data, vi) selective reporting in outcome measures and vii) selective reporting of outcomes. Potential disagreements in the assessment of risk of bias will be resolved by consensus of all authors. For outcomes that will include data from more than 10 studies subgroup analysis will be performed according to the type of study (Randomized non-randomized) as well as secondary analysis that will exclude studies of high risk of bias. Strategy for data synthesis Meta-analysis will be performed with RStudio using the meta function (RStudio Team, 2015). Confidence intervals will be set at 95%. We will calculate pooled odds ratios (OR), mean differences (MD), and 95% confidence intervals (CI) with the Hartung-Knapp-Sidik-Jonkman instead of the traditional DerSimonian-Laird random-effects model analysis (REM). The decision to proceed with this type of analysis was taken, bearing in mind recent reports that support its superiority compared to the DerSimonian-Laird model when comparing studies of varying sample sizes and between-study heterogeneity. Prediction intervals (PI) will also be calculated using the meta function in RStudio, to evaluate the estimated effect that is expected to be seen by future studies on this topic. The estimation of prediction intervals considers the inter-study variation of the results and expresses the existing heterogeneity at the same scale as the examined outcome. Trial sequential analysis To evaluate the information size, we will perform trial sequential analysis (TSA), which permits investigation of the type I error in the aggregated result of meta-analyses performed for primary outcomes that are predefined in the present meta-analysis. A minimum of three studies is considered appropriate to perform the analysis. Repeated significance testing increases the risk of type I error in meta-analyses, and TSA can re-adjust the desired significance level by using the O’Brien-Flemming a-spending function. Therefore, TSA sequential interim analyses permit the investigation of the impact of each study in the overall findings of the meta-analysis. The risk for type I errors is set at 5% and for type II errors at 20%. The TSA analysis will be performed using the TSA v. 0.9.5.10 Beta software. Analysis of subgroups or subsets Subgroup analysis is planned based on study design (RCT vs non-RCT and on chemotherapy scheme if considerable heterogeneity is reported). Contact details for further information Vasillios Pergialiotis pergialiotis@yahoo.com Organisational affiliation of the review National and Kapodistrian University of Athens Review team members and their organisational affiliations Dr Vasillios Pergialiotis. National and Kapodistrian University of Athens Dr Efstathia Liatsou. National and Kapodistrian University of Athens Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 01 October 2021 Anticipated completion date 25 November 2021 Funding sources/sponsors None Conflicts of interest Language English Country Greece Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Paclitaxel; Platinum Date of registration in PROSPERO 25 November 2021

Vasillios, P., et al. (2023). "Survival and reproductive outcomes following fertility sparing surgery for germ cell tumors."
	Review question Malignant germ cell ovarian tumors primarily affect adolescents and young adults prior to completion (or even onset) of their family planning. It is considered that even patients with advanced disease can be cured with standard chemotherapy regimens and fertility-sparing surgery appears to be safe with excellent survival after long-term follow-up that exceed 70% of cases. In the present systematic review we will summarize reproductive and survival outcomes of patients with malignant germ cell tumors treated with fertility sparing techniques. Searches We will search MEDLINE (1966–2021), Scopus (2004–2023), ClinicalTrials.gov (2008–2023), Cochrane Central Register of Controlled Trials CENTRAL (1999-2023) and Google Scholar (2004-2023) from inception until June 15 2023 for relevant articles published in languages of Latin alphabet. Keywords: germ cell; fertility sparing; ovarian cancer; survival; pregnancy Types of study to be included Randomized controlled trials, prospective and retrospective cohort studies, retrospective case control studies, case-series. Condition or domain being studied Germ cell tumors are frequently encountered in adolescent and young adults and are associated with excellent survival outcomes as even cases with advanced stage disease present excellent response to chemotherapy regimens. Current recommendations suggest that fertility sparing surgery should be performed with the aim to protect the reproductive function of these women. Several studies evaluated the impact of fertility sparing in these women and in the present systematic review we will summarize the reproductive and survival outcomes comparing them to those of women subjected to non-fertility sparing techniques. Participants/population Women with germ cell tumors undergoing surgical and medical therapy for germ cell tumors. Intervention(s), exposure(s) Women with malignant germ cell tumors subjected to fertility sparing surgery with or without adjuvant chemotherapy Comparator(s)/control Women with malignant germ cell tumors undergoing non-fertility sparing treatment (surgery and/or adjuvant chemotherapy) Main outcome(s) Live birth rates and survival outcomes (overall survival, progression free survival) Measures of effect Mean differences, odds ratios and hazards ratios Additional outcome(s) Pregnancy rates, preterm births Measures of effect Odds ratios, hazard ratios Data extraction (selection and coding) Titles and abstracts of studies retrieved using the search strategy and those from additional sources will be screened independently by two review authors to identify studies that potentially meet the inclusion criteria outlined above. The full text of these potentially eligible studies will be retrieved and independently assessed for eligibility by two review team members. Any disagreement between them concerning eligibility of particular studies will be resolved following consensus of all authors. Risk of bias (quality) assessment The methodological quality of included randomized controlled trials (RCTs) will be assessed using the Cochrane risk of bias tool. Two researchers independently evaluated the included studies based on the presence of possible selection (random sequence generation), detection (blinding of outcome assessment), performance (blinding of participants and personnel), attrition (incomplete outcome data) and reporting bias (selective reporting). The quality of non-randomized controlled studies will be assessed using the Risk Of Bias In Non-randomized Studies (ROBINS-I) tool, evaluating the possibility of bias due to confounding, selection, classification, deviation from intended intervention, missing data, measurement and reporting of the outcomes. Strategy for data synthesis Meta-analysis will be performed with RStudio using the meta function (RStudio Team, 2015). Confidence intervals will be set at 95%. We will calculate pooled odds ratios (OR) and hazard ratios (HR), mean differences (MD), and 95% confidence intervals (CI) with the Hartung-Knapp-Sidik-Jonkman instead of the traditional DerSimonian-Laird random-effects model analysis (REM). The decision to proceed with this type of analysis was taken, bearing in mind recent reports that support its superiority compared to the DerSimonian-Laird model when comparing studies of varying sample sizes and between-study heterogeneity. Evaluation of bias arising from small study effects, outliers and p-hacking will be also performed. Prediction intervals (PI) will also be calculated using the meta function in RStudio, to evaluate the estimated effect that is expected to be seen by future studies on this topic. The estimation of prediction intervals considers the inter-study variation of the results and expresses the existing heterogeneity at the same scale as the examined outcome. Trial sequential analysis To evaluate the information size, we will perform trial sequential analysis (TSA), which permits investigation of the type I error in the aggregated result of meta-analyses performed for primary outcomes that are predefined in the present meta-analysis. A minimum of three studies is considered appropriate to perform the analysis. Repeated significance testing increases the risk of type I error in meta-analyses, and TSA can re-adjust the desired significance level by using the O’Brien-Flemming a-spending function. Therefore, TSA sequential interim analyses permit the investigation of the impact of each study in the overall findings of the meta-analysis. The risk for type I errors is set at 5% and for type II errors at 20%. The TSA analysis will be performed using the TSA v. 0.9.5.10 Beta software. Analysis of subgroups or subsets Subgroup analysis will be performed if possible taking in mind: the actual histology (embryonal carcinoma, yolk sac tumor, choriocarcinoma, seminoma) the stage of the disease (early vs advanced stage) the use of adjuvant chemotherapy Contact details for further information Vasillios Pergialiotis pergialiotis@yahoo.com Organisational affiliation of the review National and Kapodistrian University of Athens Review team members and their organisational affiliations Dr Vasillios Pergialiotis. National and Kapodistrian University of Athens Mrs Kalliopi Rodolaki. National and Kapodistrian University of Athens Assistant/Associate Professor Nikolaos Thomakos. National and Kapodistrian University of Athens Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 01 June 2023 Anticipated completion date 22 July 2023 Funding sources/sponsors No funding Conflicts of interest No conflicts of interest None known Language English

Vatsa, R., et al. (2022). "Clinical pregnancy rate of women with unexplained infertility with or without cervical mucus aspiration before intrauterine insemination: A randomized controlled trial." Asian Pacific Journal of Reproduction 11(6): 247-252.
	Objective: To detect effect of removing cervical mucus before performing intrauterine insemination (IUI) on pregnancy rate in patients with unexplained infertility. Method(s): The randomized controlled trial was conducted in Infertility Division of Department of Obstetrics and Gynaecology of a tertiary care hospital. Totally 80 patients of unexplained infertility were recruited. By computer generated block randomization in block size of 4 and 6, patients were randomly allocated at time of starting ovarian stimulation into the cervical mucus removal group or the non-removal of cervical mucus group before IUI, 40 in each group. Ovarian stimulation with clomiphene 100 mg from day 2-6 of menstrual cycle along with human menopausal gonadotropin 150 IU was given alternate day starting from day 7. Follicular monitoring was done and further doses given as per response; trigger was planned when 1-3 follicle reach a diameter of >18 mm. IUI was planned after trigger. IUI was done as per the group allocated. Mucus cleaning was done in the cervical mucus removal group by aspirating mucus with IUI syringe and sterile cotton swab before IUI. The primary outcome was clinical pregnancy rate. Number of difficult IUIs and cycle cancellation due to ovarian hyperstimulation were also noted. Result(s): IUI was not done in 4 patients due to hyperstimulation. Pregnancies per IUI cycle occurred in 7.9% (3/38) in the cervical mucus removal group and 21.1% (8/38) in the non-removal of cervical mucus group. There was no statistically significant difference in clinical pregnancy rate between two groups (P=0.19). Conclusion(s): There is a trend towards a lower clinical pregnancy rate with removal of cervical mucus before IUI in women of unexplained infertility though the difference is not statistically significant. Further studies with large sample size need to be done on this intervention.Copyright © 2022 Asian Pacific Journal of Reproduction.

Vatturi, M., et al. (2020). "PND11 EFFICACY AND SAFETY OF BREXANOLONE IN THE TREATMENT OF POSTPARTUM DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS." Value Health 23: S260-None.
	
Vaudois Centre Hospitalier, U. (2021). Sacrocolpopexy Versus Sacro-spinous Fixation for Prolapse Treatment.
	No Results Available Procedure: Sacro-spinous fixation|Procedure: Subtotal hysterectomy|Procedure: Sacrocolpopexy Non inferiority of sacro-spinous fixation compared to sacrocolpopexy after 1 year|Operative time|Complications Female Not Applicable 132 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Investigator)|Primary Purpose: Treatment CHUV June 30, 2028

Vaudois Centre Hospitalier, U., et al. (2023). The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy (INCyst Trial).
	No Results Available Drug: Immunonutrition Infectious complication after cystectomy|Comprehensive Complication Index (CCI)|Mortality rate|Complication-free survival rate|Treatment compliance rate All Phase 3 232 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care INCyst October 2026

Vear, N. K., et al. (2023). "Impact of exercise and/or dietary interventions, and their behaviour change techniques, on quality of life in middle-aged and older women following treatment for cancer: A systematic review." Maturitas 175: 107783.
	Many middle-aged or older women are treated for cancer and their quality of life can be significantly impaired following treatment. Exercise and dietary interventions could address this. The aim of this review was to determine whether exercise and/or dietary interventions which are scaffolded by behaviour change theories and techniques are associated with improved quality of life in middle-aged and older women following cancer treatment. Secondary outcomes included self-efficacy, distress, waist circumference, and food variety. A search of CINAHL (EBSCOhost), Embase, MEDLINE (EBSCOhost), PsycINFO, PubMed and Scopus databases up to 17th November 2022 was conducted. A narrative summary was provided. Twenty articles discussing 18 independent randomised controlled trials/interventions were included, with a total of 1754 participants. No studies reported the outcomes of distress or food variety. Exercise and/or dietary interventions had mixed effects on quality of life, self-efficacy and waist circumference (positive effect: n = 4/14; n = 3/5; n = 4/7, respectively). Two-thirds of the interventions (exercise-only, n = 2; exercise and diet, n = 2) that demonstrated an improvement in quality-of-life scores were based upon Social Cognitive Theory. All studies that reported improvements in waist circumference employed combined exercise and dietary interventions, with individualised aspects for the dietary components. Exercise and/or dietary interventions could potentially enhance quality of life and self-efficacy, and reduce waist circumference, in middle-aged and older women treated for cancer. Although findings are currently mixed, avenues for the development of interventions include ensuring there is a theoretical underpinning and incorporating more behaviour change techniques in exercise and/or dietary interventions in this population.Copyright © 2023 The Authors

Vega-Lopez, J., et al. (2019). "Second-line treatment in recurrent urinary incontinence after the use of mid-urethral tapes. Systematic review and metaanalysis of proportions." Archivos Espanoles de Urologia 72(9): 891-903.
	
Vegas Fertility Center of, L. (2024). Lovenox With Aspirin in Thawed Blastocyst Transfer.
	No Results Available Drug: Lovenox|Drug: Aspirin|Procedure: Embryo transfer Serum hCG level Female Phase 4 130 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment FCLV 2023-2 December 15, 2024

Velez, M. P., et al. (2019). "Care plans for women pregnant using assisted reproductive technologies: a systematic review." Reproductive Health 16(1): 9.
	BACKGROUND: Between 1 and 5% of children in industrialized countries are conceived through Assisted Reproductive Technologies (ART). As infertility and the use of ART may be associated with adverse perinatal outcomes, care plans specific to these pregnancies are needed. We conducted a systematic review to examine the existing care plans specific to women pregnant following Assisted Reproductive Technologies (ART). METHODS: MEDLINE, Embase and the Cochrane Library were searched by a senior information specialist. The population of interest included women becoming pregnant with ART (e.g., Intra-Uterine Insemination, In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), and surrogacy). All proposed care plans were sought that pertained to any aspect of care during pregnancy and delivery. Only Clinical Practice Guidelines (CPGs) addressing the recommendations and plans for the care of ART pregnant women were included. The search was restricted to the publication dates 2007 to June 12, 2017 when the search was run. The search was not restricted by language, however only English and French language guidelines were considered for inclusion. RESULTS: After screening 2078 citations, a total of ten CPGs were included. The following key clinical messages were prevalent: (1) although there was no supporting evidence, antenatal care for ART pregnancies should be provided by specialist with knowledge in obstetrics; (2) high-order multiple pregnancies are the greatest risk of ART and selective reduction options should be discussed; (3) there is some evidence of increased risk of congenital abnormalities and prenatal genetic and anatomic screening is recommended, especially in IVF-ICSI pregnancies; (4) due to a lack of or conflicting evidence, treatment of venous thromboembolism, antithrombotic therapy, treatment for hypothyroidism, and women with positive thyroid antibodies is recommended to be the same as in spontaneous pregnancies; and lastly (5) since an increased level of distress is a recognized feature in these pregnancies, psychosocial care and counselling should be considered. CONCLUSIONS: There is a lack of CPGs specific to ART pregnancies. While we identified a small number of recommendations for ART pregnancies, specific interventions and models of care aiming at decreasing adverse maternal and perinatal outcomes following ART should be developed, implemented, and evaluated.

Velmurugan, H., et al. (2024). "Kisspeptin and its Current Clinical Status- A Systematic Review." Current medicinal chemistry.
	BACKGROUND: Kisspeptin was initially known as metastin for its role in suppressing metastasis in melanoma and breast cancer. Later, based on its ability to stimulate GPR54, its importance in maintaining an intact hypothalamic-pituitary-ovarian axis was recognised, which is the basis for the widespread application of the drug in several conditions such as secondary amenorrhea, regulation of puberty onset, ovarian function, trophoblast invasion, fertility regulation, parturition, and lactation. This systematic study aims to evaluate the current status of kisspentin in clinical trials. METHOD(S): The keywords 'kisspeptin' or 'metastin' were used in the clinicaltrials.gov website and Clinical Trial Registry of India (CTRI) to find eligible clinical trials or records carried out without time constraints until February 26, 2023. RESULT(S): A total of 33 records were identified through clinical trial databases. All records were screened, and four trials were rejected as they failed to meet the inclusion criteria. Finally, 29 (87.9%) reports of interventional clinical trials with kisspeptin were reviewed. CONCLUSION(S): Kisspeptin can be viewed as a multipurpose drug with considerably fewer side effects due to its effects simulating normal physiological processes in our body.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Vemuru Sudheer, R., et al. (2023). "Postoperative Outcomes After Staged Versus Coordinated Breast Surgery and Bilateral Salpingo-Oophorectomy." Annals of Surgical Oncology 30(9): 5667-5680.
	Background: The objective of this study was to compare postoperative complication rates and healthcare charges between patients who underwent coordinated versus staged breast surgery and bilateral salpingo-oophorectomy (BSO).; Patients and Methods: The MarketScan administrative database was used to identify adult female patients with invasive breast cancer or BRCA1/BRCA2 mutations who underwent BSO and breast surgery (lumpectomy or mastectomy with or without reconstruction) between 2010 and 2015. Patients were assigned to the coordinated group if a breast operation and BSO were performed simultaneously or assigned to the staged group if BSO was performed separately. Primary outcomes were (1) incidence of 90-day postoperative complications and (2) 2-year aggregate perioperative healthcare charges. Fisher's exact tests, Wilcoxon rank-sum tests, and multivariable regression analyses were performed.; Results: Of the 4228 patients who underwent breast surgery and BSO, 412 (9.7%) were in the coordinated group and 3816 (90.3%) were in the staged group. The coordinated group had a higher incidence of postoperative complications (24.0% vs. 17.7%, p < 0.01), higher risk-adjusted odds of postoperative complications [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.06-1.76, p = 0.02], and similar aggregate healthcare charges before (median charges: $106,500 vs. $101,555, p = 0.96) and after risk-adjustment [incidence rate ratio (IRR) 1.00, 95% CI 0.93-1.07; p = 0.95]. In a subgroup analysis, incidence of postoperative complications (12.9% for coordinated operations vs. 11.7% for staged operation, p = 0.73) was similar in patients whose breast operation was a lumpectomy.; Conclusions: While costs were similar, coordinating breast surgery with BSO was associated with more complications in patients who underwent mastectomy, but not in patients who underwent lumpectomy. These data should inform shared decision-making in high-risk patients. (© 2023. Society of Surgical Oncology.)

Venetis, C., et al. (2023). "Freeze-all embryos during treatment with assisted reproduction: Health economic aspects." Best Practice and Research: Clinical Obstetrics and Gynaecology 86: 102303.
	Assisted reproductive technologies are evolving, with the most recent example being the introduction of the freeze-all policy during which a fresh embryo transfer does not take place and all embryos of good quality are cryopreserved to be used in future frozen embryo transfers. As the freeze-all policy is becoming more prevalent, it is important to review the economic aspects of this approach, along with considerations of efficacy and safety, and the role of emerging freeze-all-specific ovarian stimulation strategies. Based on the available evidence, the freeze-all policy presents distinct clinical advantages, particularly for high responders. Available health economic evaluations are limited. Two good-quality cost-effectiveness analyses based on randomized controlled trials suggest that the freeze-all strategy is unlikely to be cost-effective in non-polycystic ovarian syndrome (non-PCOS), normally responding patients. However, the cost-effectiveness of the freeze-all strategy in different populations of patients and in different settings has not been evaluated, nor has the clinical and economic efficacy of modern freeze-all-specific ovarian stimulation protocols that are likely to simplify treatment and make it more affordable for patients. Economic evaluations that incorporate good practice health technology assessment (HTA) methods are needed to compare freeze-all with conventional embryo transfer strategies. Furthermore, future research should address the unique limitation of traditional HTA methods in valuing a life conceived through fertility treatment.Copyright © 2023 Elsevier Ltd

Venetis, C. A., et al. (2023). "What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis." Human Reproduction Update 29(3): 307-326.
	Background: Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety.; Objective and Rationale: A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates.; Search Methods: The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included.; Outcomes: The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates.; Wider Implications: Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Venkatesan, K., et al. (2023). "Complementary administration of curcumin in PCOS: a systematic review." Minerva Obstetrics and Gynecology 75(4): 379-386.
	Introduction: The clinical benefit of curcumin, the active ingredient in turmeric, among women diagnosed with polycystic ovarian syndrome (PCOS) is unclear. In this systematic review, we aim to provide a brief review of the existing literature on the association between curcumin supplementation and PCOS.; Evidence Acquisition: Published articles relevant to the topic was obtained through extensive search using relevant keywords such as "polycystic ovarian syndrome," "PCOS," "turmeric," and "curcumin." Inclusion criteria included studies that investigated PCOS and turmeric/curcumin, while studies that investigated the use of curcumin in other gynecological disorders, infertility, rodent studies, and non-RCTs were excluded.; Evidence Synthesis: A total of 14 articles were found and only five studies were incorporated based on the exclusion criteria. The main findings were that curcumin supplementation aids in improvement of lipid and glycemic profiles, Body Mass Index (BMI) and lowers androgen levels associated with PCOS.; Conclusions: We shed light on additional therapeutic management for PCOS other than the conventional treatment. Further studies are required with larger sample sizes and diverse patient population to derive definitive conclusions regarding benefits of curcumin supplementation in PCOS.

Venkatesh, S., et al. (2021). "A systematic review and meta-analysis of pregnancy outcomes following the retention of embryos within transfer catheters in fresh and frozen embryo transfer cycles."
	Review question [1 change] Do retained embryos within the transfer catheter during an embryo transfer procedure affect treatment outcomes Searches [1 change] The following databases will be searched: Cochrane Library Databases MEDLINE CINAHL EMBASE A grey literature search will also be conducted There will be no restriction on languages and no restrictions on date will be applied to the search to ensure maximal data collection. A combination of keyword search and MeSH terms will be used to complete the search. MeSH terms and keywords include: "Retained embryos” “Embryo Transfer” “Livebirth” “Clinical Pregnancy" “”Ectopic Pregnancy” ”Miscarriage” ”Multiple Pregnancy” Types of study to be included Randomised Studies Observational including case controlled/cohort studies Condition or domain being studied Clinical pregnancy rate and live birth rate following sequential embryo transfer due to retained embryo within the transfer catheter Participants/population Women undergoing embryo transfer Intervention(s), exposure(s) Retained embryo within the transfer catheter Comparator(s)/control [1 change] Embryo transfer not resulting in retained embryo within the transfer catheter Context Studies conducted in assisted conception units worldwide. The search incorporated studies published worldwide to ensure robust data collection with widespread applicability. Main outcome(s) Clinical pregnancy rate Measures of effect Odds Ratio/Relative Risk Additional outcome(s) [1 change] Biochemical pregnancy rate, live birth rate, ectopic pregnancy rate, miscarriage rate, multiple pregnancy rate Measures of effect Odds Ratio/Relative Risk Data extraction (selection and coding) Two reviewers (VS and VG) will independently perform a screening of titles and abstracts of studies obtained by the search strategy. Based on the pre-established inclusion criteria, full texts of potentially relevant articles will be retrieved and assessed for inclusion by two reviewers. Any discrepancies or uncertainty will disscuss with a third reviewer (SD). The following data will be extracted: Author, year of publication, Populations(country, participants numbers and the original inclusion criteria) threshold of BMI classification, and pregnancy outcome. Risk of bias (quality) assessment Two reviewers (VS VG) will independently assess the risk of bias using the Risk of Bias In Non-randomised -(ROBINS-1) tool in included studies by considering the following characteristics: -bias due to selection of participants -bias in classification of interventions -bias due to deviations from intended interventions -bias due to missing data -bias in measurement of outcomes -bias in selection of the reported results Disagreements between the review authors over the risk of bias in particular studies will be resolved by discussion, with involvements of a third review author where necessary. Two reviewers will apply the criteria independently, and discrepancies will be resolved by consensus with a third review. Publication bias will be specific funnel plots for each outcome. Strategy for data synthesis The strategy for data synthesis will be a systematic review of the literature and subsequent meta-analysis of primary studies that define the effect of abnormal BMI on the pregnancy results, in terms of live birth rate, clinical pregnancy rate, ongoing pregnancy rate, ectopic pregnancy rate, and miscarriage rate in patients with repeat embryo transfer. The magnitude of the effect of the effect will be estimated by calculating the relative risk(RR)/ odds ratio(OR) and its 95% confidence interval using logistic regression analsysis and subsequent P values for each outcome. The relative risk/odds ratio will be used to compare the described pregnancy outcomes in the exposed group (patients with abnormal BMI) versus the unexposed group(patients with normal weight). Significance level will be set at P 0.05, Heterogeneity of studies will be assessed using Higgins I². Analysis of subgroups or subsets [1 change] If possible, a subgroup analysis will be performed in order to evaluate the specific impact of factors(such as fresh or frozen embryo transfer/ number of embryos) on pooled results. Contact details for further information Venkatesh Subramanian Venki.subramanian@kingsfertility.co.uk Organisational affiliation of the review King's College London Review team members and their organisational affiliations [1 change] Dr Venkatesh Subramanian. King's College London Dr Vishalli Ghai. Epsom & St Helier University Hospitals Dr Ippokratis Sarris. King's Fertility Professor Stergios Doumouctsis. Epsom & St Helier University Hospitals Dr Janani Sakthi. Epsom & St Helier University Hospitals Dr Sesh Sunkara. King's College London Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 12 April 2021 Anticipated completion date 30 June 2021 Funding sources/sponsors

Ventura, C., et al. (2022). "The Effectiveness of Therapeutic Vaccines for the Treatment of Cervical Intraepithelial Neoplasia 3: A Systematic Review and Meta-Analysis." Vaccines 10(9).
	Cervical cancer (CC) is a disease that affects many women worldwide, especially in low-income countries. The human papilloma virus (HPV) is the main causative agent of this disease, with the E6 and E7 oncoproteins being responsible for the development and maintenance of transformed status. In addition, HPV is also responsible for the appearance of cervical intraepithelial neoplasia (CIN), a pre-neoplastic condition burdened by very high costs for its screening and therapy. So far, only prophylactic vaccines have been approved by regulatory agencies as a means of CC prevention. However, these vaccines cannot treat HPV-positive women. A search was conducted in several databases (PubMed, Scopus, Web of Science, and ClinicalTrials.gov) to systematically identify clinical trials involving therapeutic vaccines against CIN 3. Histopathological regression data, immunological parameters, safety, DNA clearance, and vaccine efficacy were considered from each selected study, and from the 102 articles found, 8 were selected based on the defined inclusion criteria. Histopathological regression from CIN 3 to CIN < 1 was 22.1% (95% CI: 0.627−0.967; p-value = 0.024), showing a vaccine efficacy of 23.6% (95% CI; 0.666−0.876; p-value < 0.001). DNA clearance was assessed, and the risk of persistent HPV DNA was 23.2% (95% CI: 0.667−0.885; p-value < 0.001). Regarding immunological parameters, immune responses by specific T-HPV cells were more likely in vaccinated women (95% CI: 1.245−9.162; p-value = 0.017). In short, these studies favored the vaccine group over the placebo group. This work indicated that therapeutic vaccines are efficient in the treatment of CIN 3, even after accounting for publication bias.

Venturella, R., et al. (2023). "Effects of relugolix combination therapy (Relugolix-CT) on uterine fibroid (UF) and uterine volume through 52 weeks: post hoc analysis of the LIBERTY Long-Term Extension study." Human Reproduction 38(Supplement 1): i117.
	Study question: How does baseline UF and uterine volume impact the proportion of women achieving meaningful UF and uterine volume reductions with Relugolix-CT through 52 weeks? Summary answer: Women with larger UF and uterine volumes at baseline may be more likely to experience clinically meaningful reductions of UF and uterine volume with Relugolix-CT. What is known already: In the randomised, Phase 3 LIBERTY 1 and 2 pivotal studies, the efficacy and safety of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) were demonstrated in premenopausal women (aged 18-50 years), with a significant reduction in UFassociated heavy menstrual bleeding (HMB) vs placebo, and preserved bone mineral density (BMD) through 24 weeks. The open-label, 28-week LIBERTY Long-Term Extension (LTE) study continued to demonstrate sustained menstrual blood loss reductions and preservation of BMD, alongside reductions in UF and uterine volume. Study design, size, duration: The LIBERTY 1 and 2 studies of Relugolix-CT were conducted in 770 premenopausal women with UF-associated HMB. Women were randomised 1:1:1 to receive Relugolix-CT or placebo for 24 weeks, or delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks). Women who completed the pivotal trials were eligible to participate in the LIBERTY LTE study, receiving open-label Relugolix-CT for an additional 28 weeks. Participants/materials, setting, methods: Endpoints of the LTE included change from baseline to Week 52 in UF and uterine volume. This post hoc analysis assessed the proportion of women who experienced a clinically meaningful reduction in UF or uterine volume of>25% or>50% through 52 weeks of Relugolix-CT. Subgroup analyses were performed to descriptively summarise the impact of UF and uterine volume at baseline (<25cm3 or>=25cm3; <300cm3 or>=300cm3, respectively) on change in UF and uterine volume. Main results and the role of chance: In total, 477 women enrolled in the LTE, 363 completed 52 weeks of treatment, and 163 received Relugolix-CT continuously up to 52 weeks. At baseline, the mean (standard deviation) volume of the largest UF was 80.0 (145.1) cm3; mean (SD) uterine volume was 386.7 (320.5) cm3 in the Relugolix-CT group. At Week 24, 52.6% and 30.3% of women in the Relugolix-CT group experienced >25% and >50% reduction in UF volume, respectively. These proportions increased to 61.1% and 36.6%, respectively, at Week 52. For uterine volume, 36.1% and 4.5% experienced a>25% and >50% reduction at Week 24, increasing to 41.2% and 9.6% at Week 52. At Week 52, of 81 women with a baseline UF volume of<25cm3, 52.4% and 27.0% experienced a>25% and >50% reduction in UF volume, respectively; 69.1% and 45.6% of 81 women with a baseline UF volume of>=25cm3 experienced >25% and >50% reductions in UF volume, respectively. At Week 52, of 96 women with a baseline uterine volume of<300cm3, 38.5% and 6.4% experienced a>25% and >50% reduction in uterine volume; 44.8% and 13.8% of 67 women with a baseline uterine volume of>=300cm3 experienced >25% and >50% reductions in uterine volume. Limitations, reasons for caution: The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. The present data are from a post hoc analysis of LIBERTY data without predefined criteria. Wider implications of the findings: Treatment with Relugolix-CT led to a substantial reduction of UF and uterine volume in a large proportion of women with UF-associated HMB. Women with larger UF and uterine volume at baseline may be more likely to experience substantial reductions of UF and uterine volume.

Venturella, R., et al. (2022). "Relugolix Combination Therapy Improves Uterine Fibroid Symptoms Independent of Fibroid Location." Obstetrics and Gynecology 139(SUPPL 1): 23S.
	INTRODUCTION: In the Phase 3, replicate, institutional review board-approved LIBERTY 1 and 2 studies, relugolix combination therapy (Relugolix CT; once daily relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) improved uterine fibroid (UF)-associated heavy menstrual bleeding (HMB), pain, and quality of life (QoL). We report the impact of location (submucosal, intramural, or subserosal) of the largest fibroid on treatment outcomes through 24 weeks. METHOD(S): Premenopausal women were randomized to relugolix combination therapy or placebo for 24 weeks. Location of the largest fibroid was investigator-defined using ultrasound; FIGO type 0/1 fibroids were excluded. Menstrual blood loss (MBL) volume was measured by alkaline hematin method (responders: MBL volume < 80mL and >=50% reduction from baseline over last 35 days of treatment). Pain and other UF-associated symptoms were evaluated using the Numerical Rating Scale and UF-QoL Questionnaire (Symptom Severity) in this post-hoc analysis. RESULT(S): In the relugolix combination therapy (N=253) and placebo (N=256) groups, the largest fibroid was categorized by location as subserous (N=50 and N=58), intramural (N=115 and N=130), submucosal (N=46 and N=43) or "other/unknown" (N=119 and N=106). Baseline characteristics, including MBL volume, pain and QoL scores, were similar between subgroups. In all fibroid subgroups, women randomized to relugolix combination therapy had comparable responder rates of 76.0%, 79.1%, 80.4%, and 65.6% at week 24 that were higher than with placebo: 24.1%, 16.2%, 14.0%, and 16.0% (all nominal P<.0001). Across all subgroups, women randomized to relugolix combination therapy experienced significant reductions in MBL volume, UF-associated pain and symptom severity versus placebo. CONCLUSION(S): Relugolix combination therapy improves HMB and other UF-associated symptoms independent of the location of the largest fibroid.

Venugopal, V., et al. (2022). "Perineal Massage for Prevention of Perineal Trauma and Episiotomy During Labor: A Systematic Review and Meta-Analysis." Journal of Family and Reproductive Health 16(3): 162-169.
	Objective: Vaginal births are associated with a certain degree of trauma to the genital tract, with significant short-term and long-term morbidity. Awareness of morbidity following perineal trauma has led to application of different interventions during the late first stage and second stage of labour to prevent severe perineal trauma. This includes techniques such as perineal massage, warm and cold compresses, and perineal management techniques. Objective of this meta-analysis is to evaluate the effect of perineal massage during the late first stage and second stage of labour on the rate of episiotomy and risk of perineal trauma. Material(s) and Method(s): Electronic databases (PubMed, Scopus, Cochrane Library and Science Direct) were searched from inception until August 2021. We included randomized controlled trials (RCTs) which compares perineal massage during labor (i.e., intervention group) with a control group in women with singleton gestation and cephalic presentation at >=36 weeks. The primary outcome was severe perineal trauma and the rate of episiotomy. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Result(s): Ten trials including 4,088 women were analyzed. Women with perineal massage during labor had a significantly lower incidence of severe perineal trauma (RR: 0.52, 95% CI 0.29-0.94) compared to the control group. The incidence of episiotomy was lower in the perineal massage group (RR: 0.71, 95% CI 0.52-0.98 p < 0.01) but was statistically insignificant (P>0.05). Conclusion(s): The finding of meta-analysis showed that perineal massage during labor could be effective in reducing the risk of severe perineal trauma, such as third-and fourth-degree spontaneous lacerations during labor.Copyright © 2022 Tehran University of Medical Sciences.

Verastem, I., et al. (2024). A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer.
	No Results Available Drug: avutometinib|Drug: Defactinib|Drug: Pegylated liposomal doxorubicin|Drug: Paclitaxel|Drug: Topotecan|Drug: Letrozole|Drug: Anastrozole Progression Free Survival (PFS) per blinded independent central review (BICR)|Overall Survival (OS)|Progression Free Survival (PFS) per investigator assessment|Objective response rate (ORR)|Duration of Response (DOR)|Disease Control Rate (DCR)|Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)|Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites|Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites|To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30).|To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Ovarian Cancer module OV28 (QLQ-OV28). Female Phase 3 270 Industry|Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: None (Open Label)|Primary Purpose: Treatment VS-6766-301|GOG-3097|ENGOT-ov81 February 9, 2031

Verbeke, E., et al. (2022). "Cost-effectiveness of mental health interventions during and after pregnancy: A systematic review." Birth 49(3): 364-402.
	Background: Mental health problems during and after pregnancy such as depression, anxiety, post-traumatic stress disorder (PTSD), or addiction are common and can have lifelong implications for both parents and offspring. This review investigates the cost-effectiveness of interventions tackling these problems, assesses the methodological quality of included studies, and indicates suggestions for further research. Method(s): Thirteen databases were searched for economic evaluations of interventions related to antenatal, perinatal, and postnatal mental health conditions, published between 2000 and September 2021, in high-income countries. Result(s): Thirty-nine studies met all inclusion criteria. Interventions considered were screening programs, pharmacological treatments, and various forms of psychosocial and psychological support. Six studies reported that the intervention was cost-saving. Eighteen were cost-effective and seven likely to be cost-effective. Only six studies included health outcomes for the child; one study considered paternal health. The time horizon for which costs and consequences were considered was for most evaluations limited to 1 year (n = 18) or 2 years (n = 11) postpartum. Conclusion(s): Given the importance of the subject, a relatively low number of studies have investigated the cost-effectiveness of interventions tackling mental health problems during and after pregnancy. The scant evidence available suggests good overall value for money. Likely, cost-effectiveness is underestimated as costly long-term consequences on offspring are systematically excluded. No evidence was found for several frequently occurring conditions. Further research is required to obtain reliable, long-term effectiveness data and to address the methodological challenges related to measuring all relevant health outcomes for all parties affected.Copyright © 2022 Wiley Periodicals LLC.

Vercellini, P., et al. (2023). "Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?" Human Reproduction Open 2023(2): hoad008.
	Study Question: Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens?; Summary Answer: An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief.; What Is Known Already: Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted.; Study Design Size Duration: A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected.; Participants/materials Setting Methods: Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded.; Main Results and the Role of Chance: Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%).; Limitations Reasons for Caution: The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed.; Wider Implications of the Findings: Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access.; Study Funding/competing Interests: This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest.; Registration Number: N/A.; Competing Interests: E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other a thors declare they have no conflict of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Vercellini, P., et al. (2020). "Which treatments are effective for endometriosis-related infertility?" Fertility and Sterility 113(2): 328-329.
	
Verdegaal Els, M. E., et al. (2023). "Timed adoptive T cell transfer during chemotherapy in patients with recurrent platinum-sensitive epithelial ovarian cancer." Journal for Immunotherapy of Cancer 11(11).
	Background: The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL), provided that immunosuppression by myeloid-derived suppressor cells and M2 macrophages is reduced. Platinum-based chemotherapy can alleviate such immunosuppression, potentially creating a window of opportunity for T cell-based immunotherapy.; Methods: We initiated a phase I/II trial (NCT04072263) in patients with recurrent platinum-sensitive EOC receiving TIL during platinum-based chemotherapy. TILs were administered 2 weeks after the second, third and fourth chemotherapy course. Patients were treated in two cohorts with or without interferon-α (IFNa), as conditioning and TIL support regimen. The primary endpoint was to evaluate the feasibility and safety according to CTCAE V.4.03 criteria and the clinical response and immune modulatory effects of this treatment were evaluated as secondary endpoints.; Results: Sixteen patients were enrolled. TIL could be successfully expanded for all patients. TIL treatment during chemotherapy without IFNa (n=13) was safe but the combination with IFNa added to the chemotherapy-induced toxicity with 2 out of 3 patients developing thrombocytopenia as dose-limiting toxicity. Fourteen patients completed treatment with a full TIL cycle and were further evaluated for clinical and immunological response. Platinum-based chemotherapy resulted in reduction of circulating myeloid cell numbers and IL-6 plasma levels, confirming its immunosuppression-alleviating effect. Three complete (CR), nine partial responses and two stable diseases were recorded, resulting in an objective response rate of 86% (Response Evaluation Criteria In Solid Tumors V.1.1). Interestingly, progression free survival that exceeded the previous platinum-free interval was detected in two patients, including an exceptionally long and ongoing CR in one patient that coincided with sustained alleviation of immune suppression.; Conclusion: TIL therapy can be safely combined with platinum-based chemotherapy but not in combination with IFNa. The chemotherapy-mediated reduction in immunosuppression and the increase in platinum-free interval for two patients warrants further exploration of properly-timed TIL infusions during platinum-based chemotherapy, possibly further benefiting from IL-2 support, as a novel treatment option for EOC patients.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Vergote, I., et al. (2023). "ENGOT-EN20/GOG-3083/XPORT-EC-042 A PHASE 3, RANDOMIZED, PLACEBOCONTROLLED, DOUBLE-BLIND, MULTICENTER TRIAL OF SELINEXOR IN MAINTENANCE THERAPY FOR PATIENTS WITH P53 WILD-TYPE, ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA." International Journal of Gynecological Cancer 33(Supplement 4): A250.
	Introduction Selinexor is FDA-approved for use in multiple myeloma and diffuse large B-cell lymphoma. In the ENGOTEN5/ GOG-3055/SIENDO study (NCT03555422), preliminary analysis of a pre-specified exploratory subgroup of patients with TP53wt EC showed a decrease in risk for progression or death with a median PFS of 13.7 months with selinexor vs 3.7 months with placebo. of the EC molecular subtypes, TP53 wild type (wt) tumors represent 50% of advanced and recurrent tumors. Methods XPORT-EC-042 (NCT05611931) is a phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of selinexor as maintenance therapy in patients with TP53wt primary stage IV or recurrent EC, who achieved a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completing at least 12 weeks of platinum combination chemotherapy+/-immunotherapy. Among other inclusion/exclusion criteria, eligible patients must be >=18 years of age, have histologically confirmed EC, and TP53wt tumor confirmed by NGS sequencing. Patients will be randomized 1:1 with selinexor 60 mg or placebo once-weekly in 28-day cycles until progressive disease, toxicity, or 3-years if in complete response. A total of 220 patients are estimated to be enrolled globally. The primary endpoint is PFS based on RECIST v1.1 criteria as assessed by the Investigator. The key secondary endpoint is overall survival. Select secondary endpoints include safety assessments and PFS assessed by a blinded independent central review. Current Trial Status Patient enrollment is ongoing.

Vergote, I., et al. (2021). "Tisotumab vedotin versus investigator's choice chemotherapy in second- or thirdline recurrent or metastatic cervical cancer (innovaTV 301/ENGOT-cx12/GOG 3057, trial in progress)."  39(15 SUPPL).
	Background: Doublet chemotherapy (paclitaxel plus either platinum or topotecan) with bevacizumab (if eligible) is recommended for first‐line treatment of recurrent (not amenable to curative therapy) or metastatic cervical cancer (r/mCC; Tewari 2014). In the second‐line setting, there are limited data for currently available treatment options. Tisotumab vedotin (TV) is an investigational antibody‐drug conjugate (ADC) composed of a tissue factor (TF)‐directed human monoclonal antibody covalently linked to the microtubule‐disrupting agent monomethyl auristatin E (MMAE) via a protease‐cleavable linker. TV is directed to cells expressing TF and releases MMAE upon internalization, resulting in cell cycle arrest and apoptotic cell death. TV has anti‐tumor activity on multiple tumor types and kills tumor cells by direct cytotoxicity, bystander cytotoxicity, antibody‐dependent cellular cytotoxicity, antibody‐dependent cellular phagocytosis, and in a manner consistent with immunogenic cell death. In a recent phase 2 pivotal trial (innovaTV 204), TV demonstrated a clinically meaningful objective response rate (ORR) of 24% and median duration of response (DOR) of 8.3 months, as well as a manageable and tolerable safety profile with most adverse events being mild to moderate, in r/mCC patients with disease progression on or after chemotherapy. These findings support further investigation of TV in patients with r/mCC who progress on available first‐line treatment options. Methods: The innovaTV 301 trial (NCT04697628) is a global, randomized, open‐label, phase 3 clinical trial evaluating the efficacy and safety of TV in patients with previously treated r/mCC. Eligible patients must be ≥18 years, have r/mCC, and have experienced disease progression after receiving 1‐2 prior lines of therapy (either standard of care systemic chemotherapy doublet or platinum‐based therapy [if eligible; paclitaxel+cisplatin+bevacizumab, paclitaxel+carboplatin+bevacizumab, or paclitaxel+topotecan/nogitecan+bevacizumab]). Approximately 482 patients will be randomized 1:1 to receive 21‐day cycles of either TV (2.0 mg/kg IV once every 3 weeks) or investigator's choice of chemotherapy: topotecan (1 or 1.25 mg/m2 IV; Day 1 [D1] to D5 of each cycle), vinorelbine (30 mg/m2 IV; D1 and D8 of each cycle), gemcitabine (1000 mg/m2 IV; D1 and D8 of each cycle), irinotecan (100 or 125 mg/m2 IV; weekly for 28days, then every 42 days), or pemetrexed (500 mg/m2 IV, D1 of each cycle). The primary endpoint of this trial is overall survival. Key secondary endpoints are progression‐free survival, ORR, time to response, DOR, safety, and quality of life outcomes.

Vergote, I., et al. (2021). "SIENDO/ENGOT-EN5/GOG-3055: a randomized phase 3 trial of maintenance selinexor versus placebo after combination platinum-based chemotherapy in advanced or recurrent endometrial cancer." Journal of Clinical Oncology 39(15 SUPPL).
	Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Options for advanced or recurrent EC following platinum‐based therapy and/or radiotherapy are limited and prognosis remains poor. Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor in combination with low dose dexamethasone is approved for relapsed/refractory multiple myeloma. In addition, selinexor monotherapy has demonstrated broad activity in other hematologic malignancies and solid tumors. In a phase 2 study, 50 mg/m2 (80 mg) selinexor administered twice weekly demonstrated a disease control rate ( SD ≥ 12 weeks or a PR) of 35% with 2 confirmed partial responses among 23 heavily pretreated EC patients); similar results were observed in 60 pts with platinum resistant or refractory ovarian cancer (median 5 prior regimens, ORR 8%, DCR 30%) (Vergote I et al. Gynecol Oncol 2020). In the absence of approved maintenance therapies, we conducted this study to evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent EC following platinum‐based chemotherapy. Methods: This is a multicenter, double‐blind, placebo‐controlled, randomized phase 3 study in patients in partial (PR) or complete remission (CR) after completing at least 12 weeks of taxane‐platinum combination therapy for primary Stage IV disease and recurrent disease (i.e., relapse after primary therapy for early stage disease including surgery and/or adjuvant therapy). A total of 248 patients will be enrolled at 80 sites in Europe, North America, and Israel. Patients will be randomized in a 2:1 ratio to either maintenance therapy with 80 mg oral selinexor once weekly or placebo. Stratification factors include primary Stage IV versus first recurrence at the time of taxaneplatinum therapy and disease status after chemotherapy (PR vs CR). Treatment will continue until disease progression. The primary endpoint is progression free survival (PFS) per RECIST v1.1. Secondary endpoints include disease‐specific survival, overall survival, time to first subsequent therapy, time to second subsequent therapy, PFS on subsequent therapy and safety and tolerability. The study is currently open and enrolling patients.

Vergote, I., et al. (2021). "Tisotumab vedotin vs investigator's choice chemotherapy in second- or thirdline recurrent or metastatic cervical cancer (INNOVATV 301/ENGOT-CX12/GOG-3057, trial in progress)." International Journal of Gynecological Cancer 31(SUPPL 4): A129‐A130.
	Objectives Doublet chemotherapy (paclitaxel plus either platinum or topotecan) with bevacizumab (if eligible) is recommended for first‐line treatment of recurrent/metastatic cervical cancer (r/mCC; Tewari 2014). In the second‐line setting, there are limited data for available treatment options. Tisotumab vedotin (TV) is an investigational antibody‐drug conjugate directed to tissue factor. In the phase 2 pivotal trial (innovaTV 204/ENGOT‐cx6/GOG‐3023) in r/mCC patients with disease progression on or after chemotherapy, TV demonstrated clinically meaningful and durable activity (objective response rate [ORR]: 24%; median duration of response [DOR]: 8.3 months) with a manageable and tolerable safety profile. Most adverse events associated with TV were mild to moderate. These findings support further investigation of TV in patients with r/mCC who progress on first‐line treatment. Methods innovaTV 301/ENGOT‐cx12/GOG‐3057 (NCT04697628) is a global, randomized, open‐label, phase 3 trial evaluating efficacy and safety of TV in patients with previously treated r/mCC. Eligible patients are ≥18 years, have r/ mCC, and have progressed after 1‐2 prior lines of therapy (either standard of care systemic chemotherapy doublet or platinum‐based therapy with bevacizumab, if eligible). Approximately 482 patients will be randomized 1:1 to receive 21‐day cycles of TV (2.0 mg/kg IV once every 3 weeks) or investigator's choice of chemotherapy: topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint is overall survival. Key secondary endpoints are progression‐free survival, ORR, time to response, DOR, safety, and quality of life outcomes. The study is enrolling and will have sites in the USA, Europe, Japan, Latin America, Taiwan, Singapore, and South Korea. Results Not applicable. Conclusions Not applicable.

Vergote, I. B., et al. (2023). "LBA9 innovaTV 301/ENGOT-cx12/GOG-3057: a global, randomized, open-label, phase III study of tisotumab vedotin vs investigator's choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer."  34: S1276‐S1277.
	Background: Tisotumab vedotin (TV) is an investigational antibody‐drug conjugate composed of a tissue factor‐directed human monoclonal antibody covalently linked to cytotoxic MMAE. In the US, TV monotherapy received accelerated approval for the treatment of adult pts with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results of TV vs investigator’s choice of chemotherapy in pts with r/mCC following 1L therapy are presented. Methods: Eligible pts had r/mCC with disease progression on/after treatment with standard of care chemotherapy doublet ± bevacizumab ± anti‐PD‐(L)1 therapy, measurable disease per RECIST v1.1, and ECOG PS 0‐1. Pts were randomized 1:1 to TV monotherapy or investigator's choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was OS. Key secondary endpoints included PFS and confirmed ORR by investigator. Results: 502 pts were randomized (TV: 253; chemotherapy: 249); median survival follow‐up was 10.8 mo (95% CI, 10.3‐11.6). Overall, median age was 50 yrs (range: 26‐80); arms were balanced for demographics and disease characteristics. 63.9% and 27.5% of pts had prior bevacizumab and prior anti‐PD‐(L)1 therapy, respectively. The TV arm had a 30% reduction in risk of death vs chemotherapy (HR 0.70; 95% CI 0.54‐0.89; P=0.0038), with significantly longer median OS (11.5 mo [95% CI 9.8‐14.9] vs 9.5 mo [95% CI 7.9‐10.7]). PFS was superior in the TV vs chemotherapy arm (HR: 0.67 [95% CI, 0.54‐0.82]; P<0.0001). Confirmed ORR was 17.8% and 5.2% in the TV and chemotherapy arms, respectively (odds ratio: 4.0; 95% CI, 2.1‐7.6; P<0.0001). Most pts experienced at least 1 treatment‐related adverse event (TV: 87.6% [grade ≥3: 29.2%] vs chemotherapy: 85.4% [grade ≥3: 45.2%]). AEs were consistent with the known TV safety profile, including for ocular, peripheral neuropathy, and bleeding AEs. Conclusions: In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR vs chemotherapy, with a manageable and tolerable safety profile in pts with 2L/3L r/mCC. Clinical trial identification: SGNTV‐003; Amendment 3 (6 April 2022), NCT04697628. Editorial acknowledgement: The authors thank Jennifer Yang, PhD, of Seagen Inc., who provided medical writing and editorial support in accordance with Good Publication Practices. Legal entity responsible for the study: Seagen Inc. Funding: This study was funded by Genmab (Copenhagen, Denmark), Seagen Inc. (Bothell, WA, USA), the Gynecologic Oncology Group (GOG), and the European Network of Gynaecological Oncological Trial Groups (ENGOT). Tisotumab vedotin is being co‐developed by Genmab and Seagen. Disclosure: I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021‐2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann‐La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021‐2022), Jazzpharma (2021‐2022), Karyopharm (2021), MSD (2021‐2022), Novocure (2020‐2022), Novartis (2021), Oncoinvent AS (2021‐2022), Seagen (2021), Sotio a.s. (2021‐2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019‐2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann‐La Roche Ltd (2019‐2020), Genmab (2019‐2020), GSK (2019‐2020), Mersana (2020), MSD (2019‐2020), Oncoinvent AS (2019‐2020), Sotio a.s. (2019‐2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Oncoinvent AS (2019‐2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored rese rch: Amgen (2019‐2020), Roche (2019‐2020). A. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, GENMAB, Alkermes, Sutro, Roche, Sotio, PharmaMar, ONCOINVENT, Novartis, Mersana, MSD, Macrogenics, Eisai, Inmunogen, Regeneron, HederaDx, Illumina, Tubulis; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, CLOVIS, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43‐SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK‐O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB‐500 phase III trial: Aravive. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, Travel Expense: Clovis; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Coordinating PI: AstraZeneca; Non‐Financial Interests, Leadership Role: GOTIC. E. Kalbacher: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, Sanofi, Roche, GSK Tesaro, Seagen Inc; Financial Interests, Personal, Other, Travel: GSK Tesaro, Seagen Inc. S. Ghamande: Financial Interests, Personal, Invited Speaker: Esai; Financial Interests, Personal, Advisory Board, also invited speaker: GSK; Financial Interests, Institutional, Coordinating PI, Clinical trial payments: GSK, Jounce; Financial Interests, Institutional, Coordinating PI, Clinical trial payment: Merck, Esai; Financial Interests, Institutional, Coordinating PI, clinical trial payments: Mersana, AstraZeneca; Non‐Financial Interests, Advisory Role: GOG foundation. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Immunogen, Mersana, MSD, Roche, AstraZeneca, GSK, Oncxerna, Shattuck Labs, Novartis, Epsilogen, Seagen, Eisai, Regeneron, Verastem; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview, Novacure; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Non‐Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non‐Financial Interests, Principal Investigator, ENGOT‐GYN1/ATARI phase II international trial (academic sponsored): AstraZeneca; Non‐Financial Interests, Principal Investigator, Academic sponsored trial PI (MONITOR‐UK): GSK; Non‐Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non‐Financial Interests, Leadership Role, Board Member: International Cancer Foundation (ICF). F.C. Maluf: Financial Interests, Personal, Advisory Board: MSD, BMS, AstraZeneca, Astellas, Janssen, Novartis, Roche, Pfizer, Sanofi Aventis; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, BMS, AstraZeneca, Astellas, Janssen, Novartis, Roche, Pfizer, Sanofi Aventis; Financial Interests, Personal, Other, Corporate board member: Janssen; Financial Interests, Personal, Research Funding: Janssen, MSD, BMS, AstraZeneca, Astellas, Roche, Sanofi A entis, Regeneron. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non‐Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non‐Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non‐Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non‐Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non‐Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non‐Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK; Non‐Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non‐Financial Interests, Member, Board of Directors: GCIG. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boehringer Ingelheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. E. Van Nieuwenhuysen: Financial Interests, Institutional, Advisory Board: Regeneron, Oncoinvent; Financial Interests, Institutional, Local PI: Regeneron, Oncoinvent, Roche, Seagen, Merck, Novartis; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca. L.M. Manso Sanchez: Financial Interests, Personal, Full or part‐time Employment: Univ Hospital 12 Octubre, Madrid; Financial Interests, Personal, Speaker’s Bureau: GSK, AstraZeneca, Novartis, Pfizer, Daiichi Sankyo, Roche; Financial Interests, Personal, Other, Travel: GSK, AstraZeneca, Roche. L. Woelber: Financial Interests, Personal, Advisory Board: GSK, Roche, MSD, Eisai, Seagen; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, MSD, Seagen; Financial Interests, Personal, Other, scientific board: med update GmbH; Financial Interests, Personal, Other, speaker: med publico GmbH; Financial Interests, Institutional, Coordinating PI: Seagen, Medac Oncology; Financial Interests, Institutional, Local PI: MSD, Vaccibody AS, Roche. A. Covens: Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Research Funding: GSK, Merck. E. Whalley: Financial Interests, Personal, ll or part‐time Employment: Seagen Inc; Financial Interests, Personal, Stocks or ownership: Seagen Inc. M.S.L. Teng: Financial Interests, Personal, Full or part‐time Employment: Seagen Inc; Financial Interests, Personal, Stocks or ownership: Seagen Inc. I. Soumaoro: Financial Interests, Personal, Full or part‐time Employment: Genmab; Financial Interests, Personal, Stocks/Shares: Genmab. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Eisai, GSK, Genentech, Merck, Immunogen, Novocure; Financial Interests, Personal, Other, consultant: GOG Foundation; Non‐Financial Interests, Member of Board of Directors: GOG Foundation. All other authors have declared no conflicts of interest.

Vergote, I. B., et al. (2023). "LBA9 innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator's choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer." Annals of Oncology 34(Supplement 2): S1276-S1277.
	Background: Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE. In the US, TV monotherapy received accelerated approval for the treatment of adult pts with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results of TV vs investigator's choice of chemotherapy in pts with r/mCC following 1L therapy are presented. Method(s): Eligible pts had r/mCC with disease progression on/after treatment with standard of care chemotherapy doublet +/- bevacizumab +/- anti-PD-(L)1 therapy, measurable disease per RECIST v1.1, and ECOG PS 0-1. Pts were randomized 1:1 to TV monotherapy or investigator's choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was OS. Key secondary endpoints included PFS and confirmed ORR by investigator. Result(s): 502 pts were randomized (TV: 253; chemotherapy: 249); median survival follow-up was 10.8 mo (95% CI, 10.3-11.6). Overall, median age was 50 yrs (range: 26-80); arms were balanced for demographics and disease characteristics. 63.9% and 27.5% of pts had prior bevacizumab and prior anti-PD-(L)1 therapy, respectively. The TV arm had a 30% reduction in risk of death vs chemotherapy (HR 0.70; 95% CI 0.54-0.89; P=0.0038), with significantly longer median OS (11.5 mo [95% CI 9.8-14.9] vs 9.5 mo [95% CI 7.9-10.7]). PFS was superior in the TV vs chemotherapy arm (HR: 0.67 [95% CI, 0.54-0.82]; P<0.0001). Confirmed ORR was 17.8% and 5.2% in the TV and chemotherapy arms, respectively (odds ratio: 4.0; 95% CI, 2.1-7.6; P<0.0001). Most pts experienced at least 1 treatment-related adverse event (TV: 87.6% [grade >=3: 29.2%] vs chemotherapy: 85.4% [grade >=3: 45.2%]). AEs were consistent with the known TV safety profile, including for ocular, peripheral neuropathy, and bleeding AEs. Conclusion(s): In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR vs chemotherapy, with a manageable and tolerable safety profile in pts with 2L/3L r/mCC. Clinical trial identification: SGNTV-003; Amendment 3 (6 April 2022), NCT04697628. Editorial acknowledgement: The authors thank Jennifer Yang, PhD, of Seagen Inc., who provided medical writing and editorial support in accordance with Good Publication Practices. Legal entity responsible for the study: Seagen Inc. Funding(s): This study was funded by Genmab (Copenhagen, Denmark), Seagen Inc. (Bothell, WA, USA), the Gynecologic Oncology Group (GOG), and the European Network of Gynaecological Oncological Trial Groups (ENGOT). Tisotumab vedotin is being co-developed by Genmab and Seagen. Disclosure: I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). A. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, GENMAB, Alkermes, Sutro, Roche, Sotio, PharmaMar, ONCOINVENT, Novartis, Mersana, MSD, Macrogenics, Eisai, Inmunogen, Regeneron, HederaDx, Illumina, Tubulis; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, CLOVIS, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB-500 phase III trial: Aravive. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, Travel Expense: Clovis; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. E. Kalbacher: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, Sanofi, Roche, GSK Tesaro, Seagen Inc; Financial Interests, Personal, Other, Travel: GSK Tesaro, Seagen Inc. S. Ghamande: Financial Interests, Personal, Invited Speaker: Esai; Financial Interests, Personal, Advisory Board, also invited speaker: GSK; Financial Interests, Institutional, Coordinating PI, Clinical trial payments: GSK, Jounce; Financial Interests, Institutional, Coordinating PI, Clinical trial payment: Merck, Esai; Financial Interests, Institutional, Coordinating PI, clinical trial payments: Mersana, AstraZeneca; Non-Financial Interests, Advisory Role: GOG foundation. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Immunogen, Mersana, MSD, Roche, AstraZeneca, GSK, Oncxerna, Shattuck Labs, Novartis, Epsilogen, Seagen, Eisai, Regeneron, Verastem; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview, Novacure; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): AstraZeneca; Non-Financial Interests, Principal Investigator, Academic sponsored trial PI (MONITOR-UK): GSK; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Leadership Role, Board Member: International Cancer Foundation (ICF). F.C. Maluf: Financial Interests, Personal, Advisory Board: MSD, BMS, AstraZeneca, Astellas, Janssen, Novartis, Roche, Pfizer, Sanofi Aventis; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, BMS, AstraZeneca, Astellas, Janssen, Novartis, Roche, Pfizer, Sanofi Aventis; Financial Interests, Personal, Other, Corporate board member: Janssen; Financial Interests, Personal, Research Funding: Janssen, MSD, BMS, AstraZeneca, Astellas, Roche, Sanofi Aventis, Regeneron. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boehringer Ingelheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. E. Van Nieuwenhuysen: Financial Interests, Institutional, Advisory Board: Regeneron, Oncoinvent; Financial Interests, Institutional, Local PI: Regeneron, Oncoinvent, Roche, Seagen, Merck, Novartis; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca. L.M. Manso Sanchez: Financial Interests, Personal, Full or part-time Employment: Univ Hospital 12 Octubre, Madrid; Financial Interests, Personal, Speaker's Bureau: GSK, AstraZeneca, Novartis, Pfizer, Daiichi Sankyo, Roche; Financial Interests, Personal, Other, Travel: GSK, AstraZeneca, Roche. L. Woelber: Financial Interests, Personal, Advisory Board: GSK, Roche, MSD, Eisai, Seagen; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, MSD, Seagen; Financial Interests, Personal, Other, scientific board: med update GmbH; Financial Interests, Personal, Other, speaker: med publico GmbH; Financial Interests, Institutional, Coordinating PI: Seagen, Medac Oncology; Financial Interests, Institutional, Local PI: MSD, Vaccibody AS, Roche. A. Covens: Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Research Funding: GSK, Merck. E. Whalley: Financial Interests, Personal, Full or part-time Employment: Seagen Inc; Financial Interests, Personal, Stocks or ownership: Seagen Inc. M.S.L Teng: Financial Interests, Personal, Full or part-time Employment: Seagen Inc; Financial Interests, Personal, Stocks or ownership: Seagen Inc. I. Soumaoro: Financial Interests, Personal, Full or part-time Employment: Genmab; Financial Interests, Personal, Stocks/Shares: Genmab. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Eisai, GSK, Genentech, Merck, Immunogen, Novocure; Financial Interests, Personal, Other, consultant: GOG Foundation; Non-Financial Interests, Member of Board of Directors: GOG Foundation. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Vermeulen Carolien, K. M., et al. (2023). "The effectiveness and safety of laparoscopic uterosacral ligament suspension: A systematic review and meta-analysis." BJOG : an international journal of obstetrics and gynaecology 130(13): 1568-1578.
	Background: Laparoscopic uterosacral ligament suspension (LUSLS) is a technique to correct apical pelvic organ prolapse (POP) by shortening the uterosacral ligaments with sutures.; Objective: A systematic review with meta-analysis of the effectiveness and safety of LUSLS as treatment for apical POP.; Search Strategy: PubMed and Cochrane search using 'pelvic organ prolapse', 'laparoscopy' and 'uterosacral', including synonyms.; Selection Criteria: All articles in English presenting outcome of an original series of women with LUSLS as treatment of apical POP. Case reports were excluded.; Data Collection and Analysis: Study enrollment was performed by two reviewers. Our primary outcome measures were objective and subjective effectiveness of the procedure. Secondary outcome measures regarded complications and recurrence. Bias was assessed with the Newcastle Ottawa Scale.; Main Results: Of 138 hits, 13 studies were included with 933 LUSLS patients. The average follow-up was 22 months. All were nonrandomised cohort studies. The pooled anatomic success rate is 90% for all LUSLS procedures (95% confidence interval [CI] 83.3-95.5). LUSLS with hysterectomy resulted in an anatomic success rate of 96.6% (95% CI 87.5-100) and LUSLS with uterus preservation 83.4% (95% CI 67.7-94.6). The pooled subjective cure rate was 90.5% (95% CI 81.9-96.5). The rate of major complications was 1%.; Conclusions: Laparoscopic uterosacral ligament suspension (with or without uterus preservation) seems to be an effective and safe treatment for women with apical POP, but long-term prospective trials and randomised controlled trials are necessary to confirm these findings. (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Verona Universita, d. (2022). Effects of Vitamin D, Epigallocatechin Gallate, Vitamin B6, and D-Chiro-inositol Combination on Uterine Fibroids.
	No Results Available Dietary Supplement: Combination of Epigallocatechin gallate, vitamin D, vitamin B6, and D-Chiro-inositol|Other: Placebo Symptoms related to uterine fibromatosis (UFS-QoL questionnaire)|The proportion of patients who refuse surgery due to regression of symptoms.|Volume of the larger fibroid|Quality of life (UFS-QoL questionnaire)|The total score obtained in the Menstrual assessment chart|The total score obtained in the Pad test|Proportion of patients who reported side effects or who stopped taking the treatment Female Not Applicable 108 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment DEFIB December 2024

Verona Universita, d. (2023). Uterine Manipulator Versus no Uterine Manipulator in Endometrial Cancer Trial.
	No Results Available Device: Uterine manipulator use Recurrence-free survival|Cause-specific survival|Overall survival|Site-specific recurrence-free survival|Operative time|Intraoperative blood loss|30-day post-surgical morbidity|Lymphovascular space invasion|Peritoneal cytology|Quality of life indexes Female Not Applicable 1030 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Treatment MANEC Trial December 31, 2031

Verpalen Inez, M., et al. (2019). "Magnetic resonance-high intensity focused ultrasound (MR-HIFU) therapy of symptomatic uterine fibroids with unrestrictive treatment protocols: A systematic review and meta-analysis." European journal of radiology 120: 108700.
	Purpose: Reevaluation of the effectiveness of Magnetic Resonance-High Intensity Focused Ultrasound (MR-HIFU) therapy for uterine fibroids by excluding studies with restrictive treatment protocols that are no longer used.; Methods: The National Guideline Clearinghouse, Cochrane Library, TRIP, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) databases were searched from inception until the 22nd of June 2018. Keywords included "MR-HIFU", "MRgFUS", and "Leiomyoma". Only studies about MR-HIFU treatment of uterine fibroids with at least three months of clinical follow-up were evaluated for inclusion. Treatments with ultrasound-guided HIFU devices or protocols not aiming for complete ablation were eliminated. The primary outcome was the improvement in fibroid-related symptoms. Technical outcomes included screening and treatment failures, treatment time, application of bowel-interference mitigation strategies and the Non-Perfused Volume (NPV) percentage. Other secondary outcomes were the quality of life, fibroid shrinkage, safety, re-interventions, reproductive outcomes, and costs. Meta-analysis was performed using a random-effects model (DerSimonian and Laird).; Results: A total of 18 articles (1323 treated patients) met the inclusion criteria. All selected studies were case series except for one cross-over trial. Overall, the quality of the evidence was poor to moderate. The mean NPV% directly post-treatment was 68.1%. The use of bowel-interference mitigation strategies may lead to increased NPV%. The mean symptom reduction at 12-months was 59.9% and fibroid shrinkage was 37.7%. The number of adverse events was low (8.7%), stratification showed a difference between HIFU systems. The re-intervention percentage at 3-33.6 months follow-up ranged from 0 to 21%. Longer follow-up was associated with a higher risk at re-interventions. Reproductive outcomes and costs couldn't be analyzed.; Conclusions: Treatment guidelines aiming for complete ablation enhanced the effectiveness of MR-HIFU therapy. However, controlled trials should define the role of MR-HIFU in the management of uterine fibroids. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Veth, V. B., et al. (2021). "Gonadotrophin-releasing hormone analogues for endometriosis." Cochrane Database of Systematic Reviews 2021(7): CD014788.
	Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effectiveness and safety of gonadotrophin-releasing hormone analogues (GnRHas) in the treatment of endometriosis.Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Vias, P., et al. (2021). "A prospective randomized trial comparing accelerated concurrent chemoradiotherapy with conventional concurrent chemoradiotherapy in locally advanced carcinoma cervix (IIA-IVA)." Journal of cancer research and therapeutics 17(4): 1012-1016.
	INTRODUCTION: Cervical cancer ranks fourth in women worldwide. The management requires a multidisciplinary approach. Concomitant chemoradiotherapy with cisplatin, followed by brachytherapy, is the standard approach. Accelerated radiotherapy (ART) can be used to decrease the treatment duration which can further lead to better outcomes. MATERIALS AND METHODS: Stages II, III, and IVA of carcinoma cervix were studied for 1 year. Ninety patients were randomized in control and study arms, 45 patients in each arm. The total dose of radiation was 50 Gy/25#/5 weeks from Monday to Friday in the control arm and 50 Gy/25#/4 weeks from Monday to Saturday in the study arm, with injection cisplatin 40 mg/m 2 intravenous infusion weekly in both the arms. RESULTS: The response was similar in both the arms at the first follow-up as well as at median follow-up. However, acute toxicities in the ART arm were more, but they were managed conservatively. CONCLUSION: ART can be used in patients of cervical cancers to decrease the total treatment time. The results were similar in both the groups but need to be studied over more number of patients.

Vibe, G. F., et al. (2021). Maternal Mental Health Trial.
	The MAMA Trial is a double-blind, 1:1 randomised, placebo-controlled trial. The trial involves maternity wards at three university hospitals in the Capital Region of Denmark. Women who are singleton pregnant in the third trimester with a prior history of perinatal depression are eligible to participate. Participants will be randomised to either estradiol patches (200 μg per day) or placebo patches for three weeks starting immediately postpartum. The primary statistical analysis will be performed based on the intention-to-treat principle. A sample size of 220 will provide the trial with 80% power (alpha 0.05, beta 0.2) to detect a reduction in postpartum depression of 50% and to tolerate a drop-out of around 20%. Primary Purpose : Prevention Allocation : Randomized Interventional Model : Parallel Assignment Masking : Quadruple (ParticipantCare ProviderInvestigatorOutcomes Assessor)

Victoria, F., et al. (2022). "Myo-Inositol for Polycystic Ovary Syndrome."
	
Victoria, S., et al. (2022). "Fresh versus frozen semen donor samples for human artificial insemination: A Systematic Review."
	
Vidal, C., et al. (2023). "Intentional endometrial injury significantly improves ongoing pregnancy rates of an oocyte donation program in patients without recurrent implantation failure (RIF): a randomized controlled trial." Human Reproduction 38(Supplement 1): i56-i57.
	Study question: Is endometrial scratching a useful add-on to be applied in assisted reproduction patients without recurrent implantation failure (RIF)? Summary answer: Endometrial scratching results in significantly higher clinical and ongoing pregnancy rates per intention to treat (ITT) among women undergoing oocyte donation without RIF. What is known already: The effect of endometrial injury or endometrial scratch (ES) on reproductive outcomes has been widely studied by randomized controlled trials but from the information obtained regarding its benefit on improving endometrial receptivity remains controversial. Oocyte donation programs (OD) provides with the ideal setting for this research, as the recipient's endometrial priming guarantees the homogeneity of the endometrium avoiding a deleterious differential effect of the stimulation on endometrial receptivity and makes comparable the quality of the oocytes and transferred embryos, then limiting the confounding factors involved in studies with autologous oocytes and their frozen surplus embryos, better addressing the research question. Study design, size, duration: A multicentric, open-label, randomized controlled trial has been conducted in a private setting from Oct 2013-Nov 2022. Eligible recipients were randomly assigned in a 1:1 ratio to either ES (by pipelle biopsy in the luteal phase of the menstrual cycle prior to the embryo transfer, n=303) or no intervention (NES, n=310), through a computergenerated randomization list, and embryo transfers (ET) performed in the cycle following the intervention. Participants/materials, setting, methods: 18-44 years aged ovum recipients with preserved ovarian function, 19-29.9 kg/m2, first/ second OD fresh embryo transfer, endometrial thickness > 6 mms, and 1-2 optimal quality blastocysts transferred. Exclusion: any adverse condition, RIF with OD, ET not performed in the cycle following the intervention. Outcomes included ongoing implantation rate (ongoing sacs/ embryo transferred), biochemical, clinical and ongoing pregnancy rates analyzed per ITT basis and per protocol strictly completed (PP, treatment correctly received, embryo transfer achieved). Main results and the role of chance: A total number of 458 recipients underwent OD-embryo transfer, 226 in scratching arm and 232 in the NES group. No differences existed in mean age and BMI of recipients and oocyte donors, oocytes retrieved and microinjected, fertilization rates, blastocysts transferred, endometrial thickness and estradiol /progesterone levels after their endometrial priming, nor other clinically relevant parameters. The biochemical pregnancy rate was 62.6%95%CI(56.6-68.3) and 55.6%95%CI(49.7-61.3) in the ES arm and in NES arm on the ITT analysis (OR 1.073 95%CI(0.990-1.163), p=0.088); and 75.3%95%CI(69.0-80.7) vs. 70.7%95%CI(64.3-76.4), respectively PP (OR1.048 95%CI(0.965-1.137), p=0.266. The clinical pregnancy rate was 57.1%95%CI(51.0-63.1) and 47.5% 95%CI(41.7-53.3) in the ES arm and in NES arm on the ITT analysis (OR=1.102 95%CI(1.015-1.196); p=0.021), and in the per protocol analysis, 68.6% 95%CI(62.0-74.6) vs 60.3%95%CI(53.7-66.6) respectively, OR=1.086 95%CI(0.995-1.186), p=0.066. The ongoing pregnancy rate was 45.1%95%CI(39.1-51.2) and 36.3% 95%CI(30.8-42.1) in the ES arm and in NES arm on the ITT analysis (OR=1.092 95%CI(1.007-1.183); p=0.033), and in the per protocol analysis, 53.8%95%CI(47.0-60.5) vs 46.1%95%CI(39.6-52.8) respectively, OR=1.080 95%CI(0.985-1.184), p=0.101. The ongoing implantation rate was in the PP analysis, 61.4%95%CI(55.1-67.8) in ES, and 56.5%95%CI(50.1-68.2) in NES respectively, p=0.276, while in the ITT analysis, 51.3% 95%CI(45.4-57.2) vs 44.4% 95%CI(38.7-50.1), p=0.098 in the ES arm and in NES arm. Limitations, reasons for caution: The number of patients not fulfilling the complete procedure probably avoided to find significant differences on the PP analysis, and during the study, there may be some clinical and/or laboratory changes through the years, that should have been affecting outcomes on both groups. Wider implica ions of the findings: This RCT shows that ES in the luteal phase of the cycle preceding the OD embryo transfer in recipients without RIF would pose a significant benefit thus its consideration for all IVF patients can be advised at this point.

Vieira Ana Glenda, S., et al. (2023). "Adjuvant chemotherapy does not improve outcome in children with ovarian immature teratoma: A comparative analysis of clinical trial data from the Malignant Germ Cell International Consortium." Pediatric blood & cancer 70(8): e30426.
	Background/objectives: Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom.; Design/methods: From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS).; Results: Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p = .05), stage II-IV EFS: 67% versus 79% (p = .32), stage II-IV OS: 93% versus 97% (p = .44); amongst grade-3 patients, there was no difference in EFS or OS.; Conclusion: Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone. (© 2023 Wiley Periodicals LLC.)

Vienna Medical University, o. (2021). Continuous Stitches Versus Simple Interrupted Stitches for Anterior Colporrhaphy.
	No Results Available Procedure: Anterior colporrhaphy subjective symptom improvement|anatomical outcomes|rate of adverse events|operation time|blood loss|pain killers Female Not Applicable 48 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Double (Participant, Outcomes Assessor)|Primary Purpose: Treatment Sutures in colporrhaphy July 1, 2023

Vienna Medical University, o. (2022). Conventional Laparoscopy Versus Robotic Surgery for Pain Relief in Patients With Deep Infiltrating Endometriosis.
	No Results Available Procedure: robotic-assisted laparoscopy|Procedure: Conventional laparoscopy Change in Visual analog scale (VAS) from baseline to 3 and 6 months after the operation|Pain medication|Menstrual bleeding|Patients' Global Impression of Change (PGIC)|Change in Biberoglu and Behrman (B&B) score from baseline to 3 and 6 months after the operation|rate of intraoperative adverse events|rate of postoperative adverse events|operation time|length of hospitalization (following the operation)|blood loss|laparotomic conversion rate|change of the Endometriosis Health Profile (EHP) EHP-30 from baseline to 3 and 6 months after the operation|10-point Likert scale for cosmetic satisfaction|Disease recurrence rate up to 12 months after surgery Female Not Applicable 50 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment TIE pain robotic vs. LSK December 31, 2023

Vienna Medical University, o. (2022). Evaluating Ovarian Reserve After Conventional Laparoscopy Versus Robotic Surgery for Bilateral Endometrioma.
	No Results Available Procedure: robotic-assisted laparoscopy|Procedure: Conventional laparoscopy Change in serum AMH (sAMH) from baseline to 6 months after the operation|Change in antral follicle count (AFC) from baseline to 6 months after the operation|change in ovarian volume from baseline to 6 months after the operation|change in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from baseline to 6 months after the operation|rate of intraoperative adverse events|rate of postoperative adverse events|operation time|length of hospitalization (following the operation)|blood loss|laparotomic conversion rate|follicle number in the histologic tissue sections|change of the Endometriosis Health Profile (EHP) EHP-30 from baseline to 6 months after the operation|10-point Likert scale for cosmetic satisfaction|Disease recurrence rate up to 12 months after surgery Female Not Applicable 104 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment AMH robotic LSK December 31, 2023

Vienna Medical University, o. (2023). PDS Versus Prolene as Suture Material for Vaginal Sacrospinous Hysteropexy.
	No Results Available Procedure: sacrospinous hysteropexy German pelvic floor questionnaire (subjective symptom improvement)|anatomical outcomes - POP-Q measurement|anatomical outcomes - ultrasound imaging|German pelvic floor questionnaire (condition-specific quality of life)|Clavien Dindo Scale for adverse events|Mini Nutritional Assessment|Visual Analog Scale|Numerical Rating Scale|Patient Impression of Improvement Index Female Not Applicable 52 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Participant)|Primary Purpose: Treatment 2079 December 2025

Vigueras, S., et al. (2020). "Diaphragmatic endometriosis minimally invasive treatment: a feasible and effective approach." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 41(2): 1-11.
	The present review aims to analyse the current data available on the feasibility, safety and effectiveness of the minimally invasive surgical (MIS) treatment of diaphragmatic endometriosis (DE). Through the use of PubMed and Google Scholar database, we conducted a literature review of all available research related to diagnosis and treatment of DE, focussed on the minimally invasive techniques. The studies were selected independently by two authors according to the aim of this review. DE is an under-diagnosed disease affecting between 0.1% and 1.5% of fertile women. It is predominantly multiple, asymptomatic and highly associated with pelvic disease in about 50-90%. MIS techniques seems to be safe, effective and feasible in tertiary advanced endometriosis centre, offering definitive advantages in terms of hospital stay, post-operative pain and return to normal activity by using several surgical techniques as hydro-dissection plus resection, laser CO2 vaporisation, electrical fulguration, Sugarbaker peritonectomy, partial (shaving) and full-thickness diaphragmatic resection. Symptoms control range from 85% to 100%, with less than 3% of conversion, peri-operative complications and recurrence rate. All cases must be performed by multidisciplinary teams including at least a gynaecologist, thoracic surgeon and anaesthetist. The lack of prospective evaluation of DE interferes with the understanding about the natural history of disease and treatment results. Therefore, the development of adequate evidence-based recommendations about diagnosis, management and follow-up is difficult at this moment.

Viktória, P., et al. (2022). "Effects of melatonin supplementation on sleep patterns and psycho-social distress in women undergoing assisted reproductive treatment - A systematic review and meta-analysis."
	
Vincentius Edwin, P., et al. (2023). "Transdermal Testosterone Therapy for Sexual Dysfunction among Menopausal Women: a Systematic Review and Meta-analysis."
	
Violante, D., et al. (2022). "The efficacy of dienogest in reducing recurrence and pain after surgical treatment of endometriosis: A systematic review and meta-analys."
	
Viotti, M., et al. (2023). "Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy." Fertility and Sterility 120(5): 957-966.
	Objective: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy.; Design: Analysis of data collected between 2017 and 2023.; Setting: Multicenter.; Patients: Patients of infertility treatment.; Intervention: Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result.; Main Outcome Measures: Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation.; Results: Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5).; Conclusion: Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic.; Competing Interests: Declaration of interests M.V. has nothing to disclose. E.G. has nothing to disclose. J.A.G. has nothing to disclose. M.M. has nothing to disclose. C.L. reports Patent application - Detection of structural aberrations in embryos, Patent application -Method for non-invasive preimplantation genetic diagnosis. M.C. has nothing to disclose. S.K. has nothing to disclose. P.Y. has nothing to disclose. N.K. has nothing to disclose. L.C. has nothing to disclose. A.B. has nothing to disclose. E.H.C. has nothing to disclose. C.Y.S. has nothing to disclose. M.S.L. has nothing to disclose. M.D.B. has nothing to disclose. A.R.C. reports honoraria from CooperSurgical and Ferring; leadership or board position Midwest Reproductive Society International, Sunfish, and Celmatix; stock Kindbody, Sunfish, Celmatix. Author Besser report honoraria from American Society for Reproductive Medicine, American College for Medical Genetics, Canadian Fertility and Andrology Society, Illinois Society of Genetic Professionals, Collaborative Group of the Americas on Inherited Colorectal Cancer, and National Society of Genetic Counselors; travel support from Collaborative Group of the Americas on Inherited Colorectal Cancer and American College for Medical Genetics; board member Genetic Counseling Professional Group (ASRM), Patient Education Committee (ASRM), International Registry of Mosaic Embryo Transfers. D.K.G. reports funding from Cooper Surgical and Igenomix for the submitted work; funding from Cooper Surgical; consulting fees from Care Fertility; honoraria from Ferring; payment for expert testimony; travel support from Ferring; Chair of International Chromosome and genome society; stock options from Conceivable outside the submitted work. D.Y.T. has nothing to disclose F.L.B. has nothing to disclose. C.G.Z. has nothing to disclose. A.R.V. has nothing to disclose. A.G.B. has nothing to disclose. S.M. reports Patent application - Detection of structural aberrations in embryos, Patent application -Method for non-invasive preimplantation genetic diagnosis; Board Director – International Society for Preimplantation Diagnosis (PGDIS); Board Director – Canadian Fertility and Andrology Society (CFAS). F.S. has nothing to disclose. (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Virginia University, o. (2021). Relative Desirability of Metformin vs. Birth Control Pill in Treating PCOS in Women of Later Reproductive Age.
	No Results Available Drug: Metformin|Drug: Oral combined hormonal contraceptives Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ) score|Short Form (SF)-36 score|General Anxiety Disorder (GAD)-7 score|Total testosterone concentrations|Calculated free testosterone concentrations|Sex hormone binding globulin|LDL cholesterol level|HDL cholesterol level|Triglyceride level|Blood pressure|Weight|Body mass index|waist-to-hip ratio|Matsuda index|Fasting insulin|Fasting glucose|2-hour glucose level during oral glucose tolerance test|Hemoglobin A1c|Framingham risk score Female Early Phase 1 88 Other Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 21649 May 1, 2027

Virginia University, o., et al. (2022). Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion.
	No Results Available Drug: Micronized progesterone|Drug: Placebo|Drug: Flutamide|Drug: Estradiol patch Change in mean FSH concentration with progesterone administration|Change in mean LH concentration with progesterone administration Female Early Phase 1 10 Other|NIH Allocation: Randomized|Intervention Model: Crossover Assignment|Masking: Triple (Participant, Care Provider, Investigator)|Primary Purpose: Basic Science HSR200016|R01HD102060 October 1, 2025

Vissers, J., et al. (2023). "Effectiveness of laparoscopic niche resection versus expectant management in patients with unexplained infertility and a large uterine caesarean scar defect (uterine niche): protocol for a randomised controlled trial (the LAPRES study)." BMJ Open 13(7): e070950.
	Introduction: A uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after a laparoscopic niche resection concerning reduction of gynaecological symptoms in relation to baseline and concerning pregnancy outcomes. However, randomised controlled trials to study the effect of a laparoscopic niche resection on reproductive outcomes in infertile women are lacking. This study will answer the question if laparoscopic niche resection in comparison to expectant management improves reproductive outcomes in infertile women with a large uterine niche.; Methods and Analysis: The LAPRES study is a randomised, non-blinded, controlled trial, including 200 infertile women with a total follow-up of 2 years. Women with the presence of a large niche in the uterine caesarean scar and unexplained infertility of at least 1 year or failed IVF will be randomly allocated to a laparoscopic niche resection within 6 weeks or to expectant management for at least 9 months. A large niche is defined as a niche with a depth of >50% of the myometrial thickness and a residual myometrium of ≤3 mm on transvaginal ultrasound. Those receiving expectant management will be allowed to receive fertility therapies, including assisted reproductive techniques, if indicated. The primary outcome is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at 12 weeks' gestation. Secondary outcome measures are time to conception leading to a live birth, other pregnancy outcomes, received fertility therapies after randomisation, menstruation characteristics, patient satisfaction, quality of life, additional interventions, and surgical and ultrasound outcomes (intervention group). Questionnaires will be filled out at baseline, 6, 12 and 24 months after randomisation. Ultrasound evaluation will be performed at baseline and at 3 months after surgery.; Ethics and Dissemination: The study protocol was approved by the medical ethics committee of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER DUTCH TRIAL REGISTER REF NO NL6350 : http://www.trialregister.nl.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Viswanathan, M., et al. (2021). "Maternal, Fetal, and Child Outcomes of Mental Health Treatments in Women: A Meta-Analysis of Pharmacotherapy." Psychiatric research and clinical practice 3(3): 123-140.
	Objective: The authors systematically reviewed evidence on pharmacotherapy for perinatal mental health disorders.; Methods: The authors searched for studies of pregnant, postpartum, or reproductive-age women with mental health disorders treated with pharmacotherapy in MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and trial registries from database inception through June 5, 2020 and surveilled literature through March 2, 2021. Outcomes included symptoms; functional capacity; quality of life; suicidal events; death; and maternal, fetal, infant, or child adverse events.; Results: 164 studies were included. Regarding benefits, brexanolone for third-trimester or postpartum depression onset may be associated with improved depressive symptoms at 30 days when compared with placebo. Sertraline for postpartum depression may be associated with improved response, remission, and depressive symptoms when compared with placebo. Discontinuing mood stabilizers during pregnancy may be associated with increased recurrence of mood episodes for bipolar disorder. Regarding adverse events, most studies were observational and unable to fully account for confounding. Evidence on congenital and cardiac anomalies for treatment compared with no treatment was inconclusive. Brexanolone for depression onset in the third trimester or the postpartum period may be associated with risk of sedation or somnolence, leading to dose interruption or reduction when compared with placebo.; Conclusions: Evidence from few studies supports the use of pharmacotherapy for perinatal mental health disorders. Although many studies report on adverse events, they could not rule out underlying disease severity as the cause of the association between exposures and adverse events. Patients and clinicians need to make informed, collaborative decisions on treatment choices. (© 2021 The Authors. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC. on behalf of the American Psychiatric Association.)

Viswanathan, M., et al. (2023). Folic Acid Supplementation to Prevent Neural Tube Defects: A Limited Systematic Review Update for the U.S. Preventive Services Task Force.
	PURPOSE: To conduct a limited update of new evidence of the benefits and harms of folic acid supplementation for the prevention of neural tube defects (NTDs) in persons capable of becoming pregnant for the U.S. Preventive Services Task Force (USPSTF) to update its 2017 recommendation. DATA SOURCES: PubMed/MEDLINE, the Cochrane Library, Embase, and trial registries for publications from July 1, 2015, through July 2, 2021; reference lists of retrieved articles, with surveillance of the literature through February 10, 2023. STUDY SELECTION: Two investigators independently screened studies from the update search using a priori inclusion and exclusion criteria. We included English-language randomized studies and nonrandomized cohort studies with comparisons that focused on the use of folic acid supplementation (by itself or in multivitamin) for the prevention of NTD-affected pregnancies in persons capable of getting pregnant. We also evaluated studies investigating potential harms of folic acid supplementation such as maternal cancer and autism spectrum disorder. We excluded poor-quality studies, studies not conducted in very highly developed countries, and studies focusing solely on persons on antiseizure medications, persons with a history of NTDs in previous pregnancies, or persons not capable of getting pregnant. DATA EXTRACTION AND ANALYSIS: One investigator extracted data and a second checked accuracy. Two reviewers independently rated the methodological quality of the included studies based on predefined criteria. RESULTS: Twelve observational studies (reported in 13 publications) were eligible for this limited update (N=1,244,072 [from nonoverlapping cohorts]). Of these, three studies (N=990,372) reported on the effect of folic acid supplementation on NTDs. No studies reported on differences by race or ethnicity. For harms, nine studies were eligible; one randomized, controlled trial (N=431) reported on variations in twin delivery, seven observational studies (N=761,125) reported on the incidence of autism spectrum disorder, and one observational study (N=429,004) reported on maternal cancer. Regarding benefits of folic acid supplementation, two cohort studies and one case-control study in this update reported on the association between folic acid supplementation and NTDs (N=990,372). One cohort study reported a statistically significant reduced risk of NTDs associated with folic acid supplementation taken before pregnancy (adjusted relative risk [aRR]: 0.54 [95% confidence interval {CI}, 0.31 to 0.91]), during pregnancy (aRR, 0.62 [95% CI, 0.39 to 0.97]), and before and during pregnancy (aRR, 0.49 [95% CI, 0.29 to 0.83]), but for only the later of two periods studied (2006 to 2013 and not 1999 to 2005). No other statistically significant benefits were reported overall. No study reported statistically significant harms (multiple gestation, autism, and maternal cancer) associated with pregnancy-related folic acid exposure. LIMITATIONS: Interventions evaluated by included studies were restricted to folic acid supplementation and did not include interventions such as food fortification, counseling to increase dietary intake, or screening for NTDs. We did not evaluate the association between red blood cell folate concentrations and NTDs. We found limited information on differences in benefits and risks of folic acid supplementation by dose and timing. We found no information about variation in outcomes by duration of use or by race or ethnicity. Our review was designed to identify evidence that could result in a change in the 2017 USPSTF A recommendation; therefore, it focused only on studies published since 2015 and did not include the previously reviewed evidence. Ethical and logistical issues constrain the conduct of new randomized, controlled trials of folate supplementation versus placebo. All newly available evidence is observational and offers limited ability to control for confounding (including from mandatory food fortification), selection bias, recall bias, and attrition. As a result, included studies have inherent uncertainty regarding case ascertainment (for NTDs and harms) and degree of exposure (dose, timing, and duration) to folic acid supplementation. CONCLUSIONS: New evidence from observational studies provides continued evidence of benefit of folic acid supplementation for preventing NTDs and no evidence of harms related to multiple gestation, autism, or maternal cancer and is consistent with the previously reviewed evidence on this topic. The 2017 USPSTF recommendation supporting folic acid supplementation in pregnancy was based on previously reviewed evidence from a randomized, controlled trial and observational studies reporting reduced NTDs with supplementation and no consistent evidence of harms for multiple gestations, maternal adverse effects, or child respiratory illness.

Vitale Salvatore, G., et al. (2020). "Ulipristal Acetate Before Hysteroscopic Myomectomy: A Systematic Review." Obstetrical & gynecological survey 75(2): 127-135.
	Importance: Uterine leiomyomas, also referred to as myomas or fibroids, are the most common benign tumors of the reproductive tract. Ulipristal acetate (UPA) is an active selective progesterone receptor modulator used as preoperative treatment for uterine myomas.; Purpose: The aim of this review is to provide an overview of the literature about the effects of UPA administration before hysteroscopic myomectomy. The clinical question in "PICO" format was in patients affected by uterine myomas undergoing operative hysteroscopic management, "Does UPA impact the surgical outcomes?"; Evidence Acquisition: We performed a systematic literature search in PubMed/MEDLINE and Embase for original studies written in English (registered in PROSPERO CRD42018092201), using the terms "hysteroscopy" AND "ulipristal acetate" published up to March 2019. Original articles about UPA treatment before hysteroscopic myomectomy (randomized, observational, retrospective studies) were considered eligible.; Results: Our literature search produced 32 records. After exclusions, 4 studies were considered eligible for analysis. Results show that UPA does not worsen the overall technical difficulty of hysteroscopic myomectomy. Moreover, it may increase the chance of complete primary myomectomy in complex hysteroscopic procedures.; Conclusions and Relevance: Despite the positive results presented in this systematic review, low-quality evidence exists yet on the impact of UPA treatment before hysteroscopic myomectomy. High-quality prospective randomized controlled trials are required to establish the impact of UPA on surgical outcomes of patients treated for uterine myomas by hysteroscopy. Moreover, long-term outcomes of myomectomies after UPA treatment (such as frequency of myoma recurrence, recovery time, and quality of life) should be determined.

Vitale Salvatore, G., et al. (2020). "Hysteroscopic endometrial resection vs. hysterectomy for abnormal uterine bleeding: impact on quality of life and sexuality. Evidence from a systematic review of randomized controlled trials." Current opinion in obstetrics & gynecology 32(2): 159-165.
	Purpose of Review: The aim of this systematic review is to summarize the current evidence regarding the effectiveness of hysterectomy and hysteroscopic endometrial resection in improving quality of life (QoL), sexual function and psychological wellbeing of women abnormal uterine bleeding.; Recent Findings: We performed a systematic literature search in PubMed/MEDLINE and Embase for original studies written in English (registered in PROSPERO 2019 CRD42019133632), using the terms 'endometrial ablation', 'endometrial destruction', 'endometrial resection', 'hysterectomy', 'menorrhagia', 'dysfunctional uterine bleeding', 'quality of life', 'sexuality' published up to April 2019. Our literature search produced 159 records. After exclusions, nine studies were included showing the following results: both types of treatment significantly improve QoL and psychological wellbeing; hysterectomy is associated with higher rates of satisfaction; hysterectomy is not associated with a significant deterioration in sexual function.; Summary: Hysterectomy is currently more advantageous in terms of improving abnormal uterine bleeding and satisfaction rates than hysteroscopic endometrial destruction techniques. Furthermore, there is some evidence of a greater improvement in general health for women undergoing hysterectomy. However, high-quality prospective randomized controlled trials should be implemented to investigate the effectiveness of hysterectomy and endometrial ablation in the improvement of QoL outcomes in larger patient cohorts.

Vitale Salvatore, G., et al. (2020). "Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives." Translational cancer research 9(12): 7767-7777.
	Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-2092). The series “Endometrial Cancer” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare. (2020 Translational Cancer Research. All rights reserved.)

Vitale, S. G., et al. (2019). "Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition." Archives of Gynecology and Obstetrics 299(2): 299-315.
	Purpose: Gynaecological cancer management in older people represents a current challenge. Therefore, in the present paper, we aimed to gather all the evidence reported in the literature concerning gynecological cancers in the elderly, illustrating the state of art and the future perspectives. Method(s): We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS and Grey literature (Google Scholar; British Library) from January 1952 to May 2017, using the terms "ovarian cancer", "endometrial cancer", "cervical cancer", "gynecological cancers" combined with 'elderly', 'cancer', 'clinical trial' and 'geriatric assessment'. Result(s): The search identified 81 citations, of which 65 were potentially relevant after initial evaluation and met the criteria for inclusion and were analyzed. We divided all included studies into three different issue: "Endometrial cancer", "Ovarian cancer" and "Cervical cancer". Conclusion(s): The present literature review shows that, in spite of the higher burden of comorbidities, elderly patients can also benefit from standard treatment to manage their gynecological cancers. It is important to overcome the common habit of undertreating the elderly patients because they are more fragile and with a lower life expectancy than their younger counterpart. Further trials with elderly women are warranted.Copyright © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Vitale, S. G., et al. (2023). "Hysteroscopic Endometrial Ablation: From Indications to Instrumentation and Techniques-A Call to Action." Diagnostics 13(3): 339.
	The development of minimally invasive techniques has led to the creation of innovative alternatives in cases where traditional methods are not applicable. In modern gynecology, hysteroscopy has become the gold standard for the evaluation and treatment of intrauterine pathology. Endometrial ablation (EA) is a procedure that uses different types of energy to destroy the endometrium and is currently used as an alternative technique in cases of heavy menstrual bleeding when medical treatment has failed and uterine preservation is desired. The aim of this review was to evaluate the feasibility, safety, and clinical outcomes of hysteroscopic EA as an alternative in patients with abnormal uterine bleeding. A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 1994 to June 2022, to evaluate the outcomes in patients with abnormal uterine bleeding (AUB) undergoing EA using hysteroscopic and non-hysteroscopic techniques. Only scientific publications in English were included. Twelve articles on the current use of endometrial ablation were included. Data on patient symptoms, tools used for EA, primary outcomes, and adverse events were recorded. EA should be considered an effective and safe approach in the management of patients with abnormal uterine bleeding caused by benign pathology, in whom medical treatment has failed or is contraindicated. Due to the lack of evidence, it would be interesting to determine whether EA would also have a role in the treatment of women with premalignant lesions, avoiding invasive surgical procedures or medical treatment in those patients for whom hysterectomy or the use of hormonal treatment is contraindicated.Copyright © 2023 by the authors.

Vitale, S. G., et al. (2020). "From hysteroscopy to laparoendoscopic surgery: what is the best surgical approach for symptomatic isthmocele? A systematic review and meta-analysis." Archives of Gynecology and Obstetrics.
	PURPOSE: To investigate the effectiveness and risks of different surgical therapies for isthmocele in symptomatic women with abnormal uterine bleeding, infertility, or for the prevention of obstetric complications, considering safety and surgical complications. METHODS: PubMed/MEDLINE, Scopus, Embase, Science Direct, and Cochrane Library were systematically searched (n° CRD4201912035) for original articles on the surgical treatment of isthmocele published between 1950 and 2018. Data synthesis was completed using MedCalc 16.4.3. The body of evidence was assessed using the GRADE methodology. RESULTS: We retrieved 33 publications: 28 focused on a single surgical technique, and five comparing different techniques. Meta-analysis showed an improvement of symptoms in 85.00% (75.05-92.76%) of women after hysteroscopic correction, 92.77% (85.53-97.64%) after laparoscopic/robotic correction, and 82.52% (67.53-93.57%) after vaginal correction. Hysteroscopic surgery was associated with the lowest risk of complications (0.76%, 0.20-1.66%). CONCLUSIONS: We found adequate evidence supporting the use of surgery for the treatment of symptomatic isthmocele, as it was found to improve the bleeding symptoms in more than 80% of patients. Differently, we found a lack of evidence regarding the role of surgery with the purpose of improving fertility or reducing the risk of obstetric complications in women with asymptomatic isthmocele. The hysteroscopic correction of isthmocele may be the safest and most effective strategy in those patients with adequate residual myometrial thickness overlying the isthmocele. Laparoscopic and vaginal surgeries may be the preferred options for patients with a thinner residual myometrium over the defect (< 2.5 mm) and when hysteroscopic treatment is inconclusive.

Vitrolife (2021). Comparing KIDScore™ D5 and iDAScore®. The KiDA Study.
	No Results Available Device: iDAScore® Clinical pregnancy rate|Positive hCG rate per randomized patient|Rate of non-viable intrauterine pregnancies per randomized patient|Clinical pregnancy rate in patients with maternal age above 35 All Not Applicable 200 Industry Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|Primary Purpose: Treatment 1571 - KiDA December 2022

Vittrup Anders, S., et al. (2023). "Overall Severe Morbidity After Chemo-Radiation Therapy and Magnetic Resonance Imaging-Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study." International Journal of Radiation Oncology, Biology, Physics 116(4): 807-824.
	Purpose: To evaluate overall severe late morbidity (grade ≥3) in patients with locally advanced cervical cancer treated with chemo-radiation therapy and magnetic resonance image guided adaptive brachytherapy within the prospective EMBRACE-I study, and to compare the results with published literature after standard radiograph based brachytherapy (BT).; Methods and Materials: From 2008 to 2015 the EMBRACE-I study enrolled 1416 patients. Morbidity was assessed (Common Terminology Criteria for Adverse Events version 3.0) every 3 months the 1st year, every 6 months the second and third year, and yearly thereafter and 1251 patients had available follow-up on late morbidity. Morbidity events (grade 3-5) were summarized as the maximum grade during follow-up (crude incidence rates) and actuarial estimates at 3 and 5 years. To compare with the published literature on standard radiograph based BT, Common Terminology Criteria for Adverse Events scores from the EMBRACE-I study were retrospectively converted into a corresponding score in the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer system.; Results: In total, 534 severe events occurred in 270 patients; 429 events were grade 3 and 105 were grade 4 events. Actuarial estimates for grade ≥3 gastrointestinal (GI), genitourinary (GU), vaginal and fistula events at 5 years were 8.5% (95% confidence interval [CI], 6.9%-10.6%), 6.8% (95% CI, 5.4%-8.6%), 5.7% (95% CI, 4.3%-7.6%), and 3.2% (95% CI, 2.2%-4.5%), respectively. The 5-year actuarial estimate for organ-related events (GI, GU, vaginal, or fistula) was 18.4% (95% CI, 16.0%-21.2%). The 5-year actuarial estimate when aggregating all G≥3 endpoints (GI, GU, vaginal, fistulas, and non-GI/GU/vaginal) was 26.6% (95% CI, 23.8%-29.6%). Thirteen patients had a treatment-related death, 8 of which were associated with GI morbidity.; Conclusions: This report assesses severe morbidity from the largest prospective study on chemo-radiation therapy and image guided adaptive brachytherapy for locally advanced cervical cancer to date. Severe late morbidity was limited per endpoint and organ category, but considerable when aggregated across organs and all endpoints. The late morbidity results in the EMBRACE-I study compare favorably with published literature on standard radiograph based BT for GI morbidity, vaginal morbidity, and fistulas. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Vivekanandan, V., et al. (2024). "VagiBIOM Lactobacillus suppository improves vaginal health index in perimenopausal women with bacterial vaginosis: a randomized control trial." Scientific Reports 14(1): 3317.
	Bacterial vaginosis (BV) can cause vaginal dysbiosis that may influence general vaginal health and pregnancy complications. Balancing vaginal microbiome using Lactobacillus spp. may be a new way to prevent and treat mild BV. We conducted a randomized, double-blind, placebo-controlled pilot study aimed at evaluating the effect of the product VagiBIOM, a multi-Lactobacillus vaginal suppository, on peri- and premenopausal women with BV in restoring vaginal pH and overall vaginal health by resetting the vaginal microbiome composition. Sixty-six peri- and premenopausal women with BV symptoms were randomized with a 2:1 ratio to be treated with VagiBIOM or placebo suppositories. Vaginal pH, VAS itching score, total Nugent score, and vaginal health index (VHI) were measured. Vaginal microbiome changes before and after the treatment were analyzed by 16S rRNA sequencing and bioinformatics analysis. After 4 weeks of intervention with VagiBIOM or a placebo, the mean score for vaginal pH, VAS itching, and total Nugent score was significantly decreased from the baseline. Compared to the baseline scores, the VHI scores improved significantly following 28-day intervention (p < 0.001). Our results revealed two Lactobacillus species, L. hamsteri, and L. helveticus, as indicator species occurring differentially in the VagiBIOM-treated group. Furthermore, the regression and species network analyses revealed significant bacterial associations after VagiBIOM treatment. Lactobacillus hamsteri was positively associated with the Nugent score and negatively associated with vaginal pH. L. iners and L. salivarius were positively and inversely associated with VHI. As is typical, Bacteroides fragilis was positively associated with vaginal pH and negatively associated with the Nugent score. Interestingly, the Lactobacillus spp. diversity improved after VagiBIOM treatment. The VagiBIOM suppository treatment for peri- and premenopausal women with BV significantly relieved vaginal itching by decreasing vaginal pH and Nugent scores and improving the overall VHI after 4 weeks' intervention. This effect was primarily the result of VagiBIOM improving vaginal Lactobacillus diversity.Trial Registration ClinicalTrials.gov registration: NCT05060029, first registration 09/28/2021: Title: A Pilot Study to Evaluate the Efficacy and Safety of Lactobacillus Species Suppositories on Vaginal Health and pH.

Viveros-Carreño, D., et al. (2022). "Fertility-sparing surgery after neo-adjuvant chemotherapy in women with cervical cancer larger than 4 cm: a systematic review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 32(4): 486-493.
	Objective: The objective of this systematic review was to assess the oncologic and fertility outcomes of patients with cervix-confined cancer >4 cm who underwent neo-adjuvant chemotherapy followed by fertility-sparing surgery.; Methods: This study was registered in PROSPERO (registration number CRD42021254816). PubMed/MEDLINE, ClinicalTrials, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID databases were searched from inception to July 2021. The included patients were those with cancer confined to the cervix and tumor diameter >4 cm (International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3) with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent intra-venous neo-adjuvant chemotherapy followed by successful fertility-sparing surgery.; Results: The initial search identified 2990 articles. A total of 40 patients from 11 studies had attempted fertility preservation surgery (conization, simple or radical trachelectomy) and in 26 patients (65%) it was successful. All patients received platinum-based chemotherapy. A complete pathological response occurred in 56% of patients and two patients (7.7%) had a recurrence. The 4.5-year disease-free survival was 92.3% and the 4.5-year overall survival rate was 100%. Of six patients who tried to conceive, four (67%) achieved at least one pregnancy and three of the five pregnancies (60%) were pre-term deliveries (all after radical trachelectomy). All patients with recurrence received cisplatin and ifosfamide instead of cisplatin and paclitaxel, underwent non-radical surgery, and had residual disease in the final specimen.; Conclusions: Evidence for fertility-sparing surgery after neo-adjuvant chemotherapy in patients with cervical cancer and tumors >4 cm is limited, and this approach should be considered as an experimental intervention. As the use of non-radical surgery could be a risk factor, if neo-adjuvant chemotherapy is used, patients should undergo fertility-sparing radical surgery.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Viveros-Carreño, D., et al. (2023). "Definitive pelvic radiotherapy for patients with newly diagnosed stage IVB cervical cancer: a systematic review." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(7): 1057-1062.
	Objective: The objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy).; Methods: This study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered.; Results: The search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (p<0.01), 14 months versus 16 months (p value not reported), 17.6 months versus 10.6 months (p<0.01), 32 months versus 24 months (p<0.01), 17.3 months versus 10 months (p<0.01), and 41.6 months versus 17.6 months (p<0.01), and not reached versus 19 months (p=0.13) respectively, favoring the groups that received definitive pelvic radiotherapy. The high clinical heterogeneity precluded the performance of meta-analysis, and all studies were at serious risk of bias.; Conclusions: Definitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice.; Competing Interests: Competing interests: None declared. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Vlazny, D. T., et al. (2023). "Extended Full Dose Versus Low Dose Direct Oral Anticoagulants in Cancer and Overweight Patients." Blood 142: 1276.
	Background: Reduced or low‐dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at full, therapeutic doses. The real‐world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unclear. Aims: Examine the effectiveness, safety and utilization of reduced‐dose DOACs in cancer patients and overweight patients. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Patients with recurrent VTE or bleeding during the first 3 months were excluded from further analysis. After completion of anticoagulation treatment for 3 months with either rivaroxaban or apixaban, patients continuing anticoagulation were evaluated in a nested case‐control study. Results: A total of 404 patients (283 (70%) on apixaban and 121 (30%) on rivaroxaban) were identified in the low dose DOAC and 3060 in the full dose anticoagulation group. Overall, the mean age was 60.7 years (SD 14.4), mean weight was 89.9 kg (SD 23.8) and 55.1% were males. Within the full cohort, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42‐0.73; p<0.001). However, low dose DOAC prescription was more likely in patients with pulmonary embolism alone (HR 1.48; 95%CI 1.21‐1.80; p<0.001) or in combination with DVT (HR 1.54; 95%CI 1.25,1.90; p<0.001). Patients transitioned to low dose DOACs had similar age, sex and weight compared to the full dose anticoagulation group, however, fewer patients with weight ≥120 kg had reduced dosing (HR 0.68; 95%CI 0.46,0.99; p=0.046). The mean time to start of a low dose DOAC was 5.1 months overall, 5.4 months in cancer patients, and 3.6‐4.9 months in non‐cancer patients (Table 1). Non‐cancer patients had significantly lower transition numbers in those ≥120kg (HR 0.62; 95%CI 0.40,0.97; p=0.038). In non‐cancer patients In comparing weight, ≥120kg to <120kg, in the low dose group, only death was statistically different with higher risk in those ≥120kg (HR 6.44; 95%CI1.27,32.81; p=0.025). Cancer patients transitioned to low dose DOACs around 5 months on average with a median of 3.3 months. Apixaban continued to be the dominant DOAC used (78%) in the low dose group. The cancers with the most patients on low dose DOACs include lymphoma, prostate, melanoma, ovarian, and breast. There was no significant difference in VTE recurrence or death in the cancer group on different DOAC doses. Conclusion: Our results show that anticoagulant prescribers are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients despite lack of cancer‐specific studies during the analyzed time period. Although the sample size limits the precision of this analysis, we did not find statistically significant increases in VTE recurrence with low dose DOACs in either cancer patients or with elevated body weight. We did find CRNMB but not MB was observed more frequently in weights above 120kg, possibly from unadjusted confounding in this unadjusted analysis.

Vodegel, E. V., et al. (2022). "The effects of oestrogen on vaginal wound healing: A systematic review and meta-analysis." Neurourology and Urodynamics 41(1): 115-126.
	Aims: To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes. Method(s): A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges' g; SMD) and 95% confidence interval (CI) were calculated. Result(s): Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: -0.58, 95% CI: -1.14 to -0.02) in women and animals and reduces levels of transforming growth factor (TGF)-beta1 (SMD: -1.68, 95% CI: -2.52 to -0.83) in animals. All results were statistically significant. Conclusion(s): Oestrogen therapy has a positive effect on vaginal wound healing. Future studies should determine whether oestrogen therapy has the potential to improve surgical outcomes.Copyright © 2021 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

Vodegel, E. V., et al. (2021). "Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial." BMC Women's Health 21(1): 439.
	Background: Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. Method(s): The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of >= 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. Discussion(s): This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853. EudraCT: 2017-003144-21; registered: 24-07-2017.Copyright © 2021, The Author(s).

Von Aarburg, N., et al. (2021). "Physical activity and urinary incontinence during pregnancy and postpartum: A systematic review and meta-analysis." European Journal of Obstetrics and Gynecology and Reproductive Biology 267: 262-268.
	To assess the association of physical activity and urinary incontinence, or its recovery, during pregnancy and postpartum. A search of publications indexed in five major electronic databases (CENTRAL, PubMed, EMBASE, CINAHL and PEDro) was performed from their respective inception dates to the 30 March 2020 with a combination of keywords to identify studies of interest. Google Scholar was used for non-indexed literature. All studies comparing physical activity with standard care in pregnant and postpartum women were selected. Two reviewers independently selected studies, assessed quality and extracted data. Odds ratios with 95% confidence intervals were calculated using fixed effects or random effects models, for low and moderate heterogeneity between studies, respectively. Seven studies (n = 12479) were included. Data of four studies could be pooled for meta-analyses; subgroup and sensitivity analyses were not possible. Physical activity, either during pregnancy or postpartum, is not associated with urinary incontinence, OR 0.90 (95% CI: 0.69-1.18) and OR 1.31 (95% CI: 0.74-2.34), respectively. Due to a lack of available data, urinary incontinence recovering could not be assessed. The available low evidence does not show that physical activity during pregnancy or postpartum is associated with urinary incontinence. Moderate physical activity should therefore be encouraged for the evidence-based benefits on other obstetrical outcomes.Copyright © 2021 The Authors

von Deimling, M., et al. (2022). "Radical cystectomy and urinary diversion in women: techniques, outcomes, and challenges-a narrative review." Translational Andrology and Urology 11(11): 1598-1610.
	Background and Objective: Standard radical cystectomy (RC) in women includes the removal of the bladder, urethra, uterus with the adnexa, and the anterior vaginal wall, thereby severely affecting the urinary, sexual, and reproductive system. To limit these detrimental effects, organ-sparing, including nerve-sparing approaches, have been developed. Health-related quality of life (HRQOL) and functional outcomes are, indeed, becoming increasingly central to the shared decision-making with the patient. The objectives of this narrative review are: (I) to review the current status of RC in women, including the use of different urinary diversions (UDs); (II) to discuss organ-sparing approaches and their impact on oncological and functional outcomes in women; (III) to discuss the impact of RC on HRQOL and sexual function in women.; Methods: We performed a non-systematic literature review of the available publications in the PubMed database.; Key Content and Findings: Over the past years, gender differences in oncological and functional outcomes after RC have received increased attention. According to the currently available literature, organ-sparing approaches can be safely performed in well-selected women without negatively impacting oncological outcomes. The orthotopic neobladder is feasible and oncologically safe in well-selected and informed women. The choice of the UD should be based on comprehensive counseling and the patient's comorbidities and preferences. There still is a lack of data on sexual recovery after the different surgical approaches aimed to mitigate sexual dysfunction in women undergoing RC.; Conclusions: Pre-and post-operative counseling and support of females undergoing RC regarding their expectations and experiences in terms of quality of life and functional and sexual outcomes are currently insufficient. Well-designed studies in this field are necessary to further improve outcomes of women treated with RC with an overarching aim to close the gender gap in managing women with bladder cancer.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-463/coif). MR serves as an unpaid Associate Editor in Chief of Translational Andrology and Urology from January 2022 to December 2023. MP reports that he has received a research grant from the Austrian Urological Association; support for attending the Austrian Urological Association’s yearly meeting; speaker honoraria from Astellas, Janssen, and MedMedia; and an honorarium from Spectra for attending an Advisory Board. MP was a board member of the Austrian Urological Association from 2018 to 2021. The listed content regarding MP were not related to the this study. MF is a member of the Advisory Board of Boston Scientific. MF has received a grant from Boston Scientific as well as support from Astellas/Apogepha for the organization of a scientific meeting. The listed content regarding MF was not related to this study. The other authors have no conflicts of interest to declare. (2022 Translational Andrology and Urology. All rights reserved.)

Vordermark, D., et al. (2020). "The role of postoperative radiotherapy for carcinosarcoma of the uterus." Cancers 12(12): 1-10.
	The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Vuong, L. N., et al. (2023). "Outcomes of clinical IVM programs for treating infertility in hyperresponders: a systematic review." Fertility and Sterility.
	Oocyte in vitro maturation (IVM) has been proposed as an alternative to conventional ovarian stimulation (COS) in subfertile women with PCOS. To evaluate the effectiveness and safety of IVM versus COS in women with predicted hyperresponse to gonadotropins, this study searched the published literature for relevant studies comparing any IVM protocol with any COS protocol followed by IVF or ICSI. A systematic review was undertaken on three eligible prospective studies. Live birth rate was not significantly lower after IVM versus COS (odds ratio [95% confidence interval] of 0.56 [0.32-1.01] overall, 0.83 [0.63-1.10] for hCG-triggered IVM [hCG-IVM] and 0.45 [0.18-1.13] for non-hCG-triggered IVM [non-hCG-IVM]), irrespective of the stage of transferred embryos. Data from non-randomized studies generally showed either significantly lower or statistically comparable rates of live birth with IVM versus COS. The majority of studies have not identified any significant difference between IVM and COS with respect to rates of obstetric/perinatal complications, apart from a potentially higher rate of hypertensive disorders in pregnancy. The development of offspring from IVM and COS with IVF/ICSI appears to be similar. Additional research is needed to identify which patient populations will benefit most from IVM, to define the appropriate clinical protocol, and to develop the optimal culture system.

Vyrides Andreas, A., et al. (2022). "Dual Trigger with Gonadotropin Releasing Hormone Agonist and Human Chorionic Gonadotropin of Fresh Autologous Cycles in High Responders: A Systematic Review." Journal of Reproduction & Infertility 23(1): 3-17.
	Background: The purpose of the current study was to investigate the effect of co-administration of human chorionic gonadotropin (hCG) with gonadotropin releasing hormone agonist (GnRH-a) trigger (dual trigger) in high responders for fresh autologous cycles in order to investigate the pregnancy outcomes and rates of ovarian hyperstimulation syndrome (OHSS) in comparison to GnRH-a trigger alone.; Methods: A systematic search was performed in PubMed and Ovid MEDLINE from inception through February 2020. The included materials were case-control, cohort and, cross-sectional studies as well as clinical trials in which the outcomes of dual trigger with GnRH-a were compared for final oocyte maturation in high responders undergoing GnRH-ant cycles.; Results: Five retrospective studies were included for this review. Three of the studies showed that the use of dual trigger versus GnRH-a trigger resulted in no statistically significant difference in rates of OHSS while achieving a statistically significant difference in favor of the dual trigger group in ongoing pregnancy rates, early pregnancy loss, and fertilization rates.; Conclusion: Currently, there is insufficient evidence to support improved clinical pregnancy rate, fertilization rate, live birth rate, and early pregnancy loss rate by the use of dual trigger versus GnRH-a trigger. Larger double-blind clinical studies are required to properly evaluate the efficacy of this protocol for use in high responders.; Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest. (Copyright© 2022, Avicenna Research Institute.)

Waddell, G. and G. Waddell (2021). "Songs from home: addressing postnatal depression and loneliness through online songwriting." ISRCTN registry.
	
Wadensten, T., et al. (2021). "A Mobile App for Self-management of Urgency and Mixed Urinary Incontinence in Women: Randomized Controlled Trial." Journal of Medical Internet Research 23(4): e19439.
	BACKGROUND: Many women experience urgency (UUI) and mixed (MUI) urinary incontinence but commonly hesitate to seek care. Treatment access and self-management for these conditions can be supported through eHealth approaches. OBJECTIVE: This study aimed to investigate the efficacy of the mobile app Tät II for self-management of UUI and MUI in women. METHODS: This randomized controlled trial included women ≥18 years old with UUI or MUI and ≥2 leakages per week. Those with red-flag symptoms were excluded. Participants were recruited via analog and digital advertisements and screened for initial selection through a web-based questionnaire. Data were collected using another questionnaire and a 2-day bladder diary. A telephone interview confirmed the symptom diagnosis. Participants were randomized (1:1) to receive access to a treatment app (including pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, tailored advice, exercise log, reinforcement messages, and reminders) or an information app (control group), with no external treatment guidance provided. The primary outcome was incontinence symptoms at the 15-week follow-up, measured using the International Consultation on Incontinence Questionnaire (ICIQ)-Urinary Incontinence Short Form (ICIQ-UI SF). Urgency symptoms were assessed using the ICIQ-Overactive Bladder Module (ICIQ-OAB) and quality of life using the ICIQ-Lower Urinary Tract Symptoms Quality of Life Module (ICIQ-LUTSqol). Incontinence episode frequency (IEF) was calculated per bladder diary entries. Improvement was measured using the Patient's Global Impression of Improvement. All outcomes were self-reported. Cure was defined as no leakages per the bladder diary. Intention-to-treat analysis was performed. RESULTS: Between April 2017 and March 2018, 123 women (mean age 58.3, SD 9.6 years) were randomized to the treatment (n=60, 2 lost to follow-up) or information (n=63) group. Of these, 35 (28%) women had UUI, and 88 (72%) had MUI. Mean ICIQ-UI SF score at follow-up was lower in the treatment group than in the information group (estimated difference -3.1, 95% CI -4.8 to -1.3). The estimated between-group difference was -1.8 (95% CI -2.8 to -0.99) for mean ICIQ-OAB score and -6.3 (95% CI -10.5 to -2.1) for the mean ICIQ-LUTSqol score at follow-up. IEF reduction from baseline to follow-up was greater in the treatment group (-10.5, IQR -17.5 to -3.5) than in the information group (P<.001). Improvement was reported by 87% (52/60) of treatment group participants and by 30% (19/63) of information group participants. The cure rate was 32% in the treatment group, and 6% in the information group (odds ratio 5.4, 95% CI 1.9-15.6; P=.002). About 67% (40/60) of the treatment group participants used the app more than thrice a week. CONCLUSIONS: The treatment app was effective for improving urgency and mixed incontinence in women. When self-management is appropriate, this app may be a good alternative to pharmacological treatment or other conservative management, thus increasing access to care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03097549; https://clinicaltrials.gov/ct2/show/NCT03097549.

Wadensten, T., et al. (2022). "App-based self-management of urgency and mixed urinary incontinence in women: One-year follow-up." Neurourology and Urodynamics 41(4): 945-954.
	Aims: To evaluate the long-term effect of the TatII app for treatment of urgency (UUI) and mixed urinary incontinence (MUI). Method(s): Long-term follow-up of a randomized controlled trial, including 123 women >=18 years old with UUI or MUI, without red-flag symptoms, and >=2 leakages per week. All participants, regardless of group, had received the intervention, a treatment app, at the long-term follow-up. Long-term data were collected through web-based questionnaires 15 months after participants received the intervention. The app included pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, an exercise log, reminders, reinforcement messages, and tailored advice. The primary outcome was a change in incontinence symptoms (International Consultation on Incontinence Questionnaire [ICIQ]-Urinary Incontinence Short Form [ICIQ-UI SF]), from baseline to follow-up. Other outcomes were urgency symptoms (ICIQ-Overactive Bladder Module (ICIQ-OAB)), quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life Module [ICIQ-LUTSqol]), and improvement (Patient's Global Impression of Improvement [PGI-I]). Result(s): Of the 123 women, 102 (83%) completed the long-term follow-up. The ICIQ-UI SF mean score improved from 11.5 to 7.6 (mean difference 4.0, 95% CI 3.2-4.7). The ICIQ-OAB improved from 6.7 to 5.5 (mean difference 1.3, 95% CI 0.9-1.6) and the ICIQ-LUTSqol improved from 38.0 to 30.9 (mean difference 7.1, 95% CI 5.7-8.5). Of the 102 women, 74 (73%) reported improvement. Conclusion(s): Self-management with the TatII app for UUI and MUI had a significant effect across all outcome measures also long-term and might serve as an alternative first-line treatment for these conditions.Copyright © 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.

Wadephul, F., et al. (2020). "Conceptualising women's perinatal well-being: A systematic review of theoretical discussions." Midwifery 81: 102598.
	BACKGROUND: Perinatal well-being has increasingly become the focus of research, clinical practice and policy. However, attention has mostly been on a reductionist understanding of well-being based on a mind-body duality. Conceptual clarity around what constitutes well-being beyond this is lacking. AIM: To systematically review theoretical discussions of perinatal well-being in the academic literature. DESIGN AND METHODS: A search of online databases identified papers which discussed perinatal well-being theoretically, taking a multi-dimensional approach to well-being. Thematic synthesis was used to identify and synthesize relevant elements within the included papers. FINDINGS: Eight papers were identified for inclusion in this review. All contributed a number of elements towards a theoretical discussion of perinatal well-being. Three themes were developed: (1) the importance of a number of general domains of women's lives and domains specific to the perinatal period, (2) well-being as a subjective and individual experience with physical/embodied, affective, and psychological/cognitive aspects, and (3) the dynamic nature of well-being. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Perinatal well-being is a complex, multi-dimensional construct. Current theoretical discussions in the academic literature do not provide a comprehensive model or conceptualisation covering all aspects of well-being during the perinatal period. Further theoretical work is required, particularly with regards to theorising well-being during labour and birth, the perinatal period as a continuum, and the role played by women's expectations. The themes identified in this review contribute to a tentative model of perinatal well-being, taking note particularly of the dynamic nature of well-being. This model should be refined and validated through empirical work and can then be used to underpin further research and the development of a multi-dimensional measure of perinatal well-being.

Wadhwa, L. and A. Rani (2021). "Impact of Intrauterine Administration of Human Chorionic Gonadotropin before Intrauterine Insemination in Infertile Women: A Randomized Controlled Trial." Journal of human reproductive sciences 14(2): 156-161.
	BACKGROUND: Implantation is the rate-limiting step in the success of both intrauterine Insemination (IUI) and in vitro fertilization cycles. Numerous interventions that target various local signals have been tried to improve the implantation and clinical pregnancy rate (CPR). The most significant of these signals is human chorionic gonadotropin (hCG) which acts as immunomodulator and improves implantation by decidualization of the endometrial stromal cells, trophoblast invasion, proliferation of uterine natural killer cells, stimulation of endometrial angiogenesis, and maintenance of progesterone secretion by the corpus luteum. AIM: The aim of the study is to evaluate the effect of intrauterine hCG administration before IUI on CPR. SETTINGS AND DESIGN: A prospective parallel randomized control study was done from September 2017 to February 2019. MATERIALS AND METHODS: A total of 200 eligible women planned for IUI were randomly divided just before IUI into 2 groups. A computer-generated randomization list with block size of 10 with 1:1 allocation was used to randomize the patients. Experimental group received 0.5 ml containing 500 IU hCG, on the other hand control group received 0.5 ml of normal saline 2-3 min before IUI in single sitting. The main outcomes were CPR, miscarriage rate, and ongoing pregnancy rate. STATISTICAL ANALYSIS: It was performed using statistical software version SPSS 17.0. RESULTS: Patient's demographic and baseline characteristics were comparable in both the groups. CPR in experimental group was significantly high compared to control group (26% vs. 9%, P = 0.002). Ongoing pregnancy rate was also significantly higher in experimental group (23%) compared to control group (7%) (P = 0.003). No significant difference in miscarriage rate was seen between the two groups. No cases of ectopic pregnancy, ovarian hyperstimulation syndrome, or multiple pregnancy were reported. CONCLUSION: Intrauterine hCG administration is a simple procedure that can be used to improve pregnancy outcome in IUI cycles.

Waghe, T., et al. (2024). "Role of Platelet-Rich Plasma in Genitourinary Syndrome of Menopause." Cureus 16(1): e53316.
	The genitourinary syndrome of menopause (GSM) encompasses a range of symptoms linked to the genitourinary tract stemming from the reduction in estrogen levels following menopause. These symptoms may endure throughout a woman's lifetime. Platelet-rich plasma (PRP), known for its capacity to induce angiogenesis and the restoration effects of growth factors, has been widely employed in various disorders, including GSM. This article aims to comprehensively review the existing literature on the utilization of PRP for managing GSM. The search was executed in electronic databases, specifically PubMed, Scopus, and Google Scholar, up until April 2023. Eligible studies were meticulously chosen for inclusion in this systematic review. PRP emerges as a viable alternative for addressing vaginal atrophy, exhibiting favorable outcomes. Notably, it can be considered for patients with contraindications to hormonal therapy. However, the available body of evidence supporting the use of PRP for GSM remains limited. PRP presents itself as a promising agent, offering a patient-friendly, cost-effective alternative modality. To establish the efficacy of PRP in treating GSM definitively, future randomized trials are imperative.; Competing Interests: The authors have declared that no competing interests exist. (Copyright © 2024, Waghe et al.)

Wagner, B., et al. (2022). "The effect of biofeedback interventions on pain, overall symptoms, quality of life and physiological parameters in patients with pelvic pain : A systematic review." Wiener klinische Wochenschrift 134(Suppl 1): 11-48.
	Background: Biofeedback is recognized as an effective additive method for treating certain phenotypes of chronic pelvic pain syndrome and is a therapeutic option in other pelvic pain conditions. This review aims to evaluate evidence from the literature with a focus on the effect of biofeedback on pain reduction, overall symptom relief, physiological parameters and quality of life.; Methods: A systematic literature search was conducted using the databases PubMed, MEDLINE, Embase, Cochrane Library and PEDro from inception to July 2020. Data were tabulated and a narrative synthesis was carried out, since data heterogeneity did not allow a meta-analysis. The PEDro scale and the McMaster Critical Review Form-Quantitative Studies were applied to assess risk of bias.; Results: Out of 651 studies, 37 quantitative studies of primary research evaluating pelvic pain conditions in male and female adults and children were included. They covered biofeedback interventions on anorectal disorders, chronic prostatitis, female chronic pelvic pain conditions, urologic phenotypes in children and adults and a single study on low back pain. For anorectal disorders, several landmark studies demonstrate the efficacy of biofeedback. For other subtypes of chronic pelvic pain conditions there is tentative evidence that biofeedback-assisted training has a positive effect on pain reduction, overall symptoms relief and quality of life. Certain factors have been identified that might be relevant in improving treatment success.; Conclusions: For certain indications, biofeedback has been confirmed to be an effective treatment. For other phenotypes, promising findings should be further investigated in robust and well-designed randomized controlled trials. (© 2021. The Author(s).)

Wagner-Schuman, M., et al. (2023). "What's Stopping Us? Using GnRH Analogs With Stable Hormone Addback in Treatment-Resistant Premenstrual Dysphoric Disorder: Practical Guidelines and Risk-Benefit Analysis for Long-term Therapy." The Journal of Clinical Psychiatry 84(4).
	Objective: Despite the documented success of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of treatment-resistant premenstrual dysphoric disorder (PMDD), many patients struggle to find providers who have sufficient knowledge of PMDD and its evidence-based treatments and/or who are comfortable treating PMDD after first-line treatment options have failed. Here, we discuss the barriers to initiating GnRHa for treatment-resistant premenstrual dysphoric disorder (PMDD) and offer practical solutions to address these barriers for providers who encounter patients with treatment-resistant PMDD but may not have the necessary expertise or comfort with providing evidence-based treatments (ie, gynecologists, general psychiatrists). We have included supplementary materials including patient and provider handouts, screening tools, and treatment algorithms with the hope that this review may serve as a primer on PMDD and the use of GnRHa with hormonal addback as a treatment, as well as a guideline for clinicians delivering this treatment to patients in need.; Options: In addition to offering practical treatment guidelines for first and second lines of treatment for PMDD, this review offers an in-depth discussion of GnRHa for treatment-resistant PMDD.; Outcomes: The burden of illness in PMDD is estimated to be similar to that of other mood disorders, and those suffering from PMDD are at a high risk for suicide.; Evidence: We present a selective review of relevant clinical trials evidence supporting the use of GnRHa with addback hormones in treatment-resistant PMDD (the most recent evidence cited was published in 2021), highlighting the rationale for addback hormones and presenting the different possible hormonal addback approaches.; Values: The PMDD community has and continues to suffer from debilitating symptoms despite the known interventions. This article provides guidance for implementing GnRHa into practice among a broader scope of clinicians including general psychiatrists.; Benefits, Harms, and Costs: The primary benefit of implementing this guideline is that a broad range of clinicians beyond reproductive psychiatrists who encounter patients with PMDD will have a template for assessing and treating PMDD and implementing GnRHa treatment when first-line treatments fail. Harms are expected to be minimal; however, some patients may have side effects or adverse reactions to the treatment or may not respond as they had hoped. Costs of GnRHa can be high depending on insurance coverage. We provide information within the guideline to help navigate this barrier.; Recommendations: (1) Prospective symptom rating in evaluating for PMDD is necessary for diagnosis and evaluating treatment response. (2) SSRIs and oral contraceptives should be trialed as the first- and second-line treatments for PMDD. (3) When first- and second-line treatments have failed to yield symptom relief, the use of GnRHa with hormone addback should be considered. Risks and benefits of GnRHa should be weighed among clinicians and patients, and potential barriers to access should be discussed.; Validation: This article adds to the available systematic reviews on the effectiveness of GnRHa in the treatment of PMDD and Royal College of Obstetrics and Gynecology's guidelines on the treatment of PMDD. (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Waldorff, F. B., et al. (2021). "Factors associated with a clinically relevant reduction in menopausal symptoms of a standardized acupuncture approach for women with bothersome menopausal symptoms." BMC complementary medicine and therapies 21(1): 29.
	BACKGROUND: Little is known about factors associated with a clinically relevant reduction in menopausal symptoms through a brief acupuncture approach for women with moderate-to-severe menopausal symptoms. METHODS: Post hoc analysis of a randomized controlled trial where participants were allocated to early versus late standardized acupuncture. Both the early group and the late group are included in this study. The late group got an identical intervention parallel staged by 6 weeks. By means of the relative importance, the effect was evaluated for both early versus late women with a 6-week follow-up. We included four symptom subscales from the validated MenoScores Questionnaire: hot flushes, day and night sweats, general sweating, menopausal-specific sleeping problems, as well as an overall score, which is the sum of the four outcomes in the analysis. RESULTS: 67 women with moderate to severe menopausal symptoms were included of whom 52 (77.6%) experienced a clinically relevant reduction in any of the four surveyed symptom subscales or overall score. 48 (71.6%) women experienced a clinically relevant reduction in any of the vasomotor symptom subscales: hot flushes, day and night sweats, general sweating. Women with vocational education were most likely to experience improvement compared to women with higher education. Beyond education, other factors of some importance for a clinically relevant reduction were no alcohol consumption, two or more births and urinary incontinence. CONCLUSIONS: Level of education was the most consistent factor associated with improvement. Beyond education, other factors of some importance were no alcohol consumption, two or more births and urinary incontinence. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov at April 21, 2016. The registration number is NCT02746497 .

Waldron Michael, G., et al. (2022). "Uterine Artery Embolisation of Fibroids and the Phenomenon of Post-Embolisation Syndrome: A Systematic Review." Diagnostics (Basel, Switzerland) 12(12).
	Post-embolisation syndrome (PES) is a prevalent complication that occurs in patients following uterine artery embolisation (UAE) for the treatment of uterine fibroids. The aetiology of PES remains incompletely understood, although postulated to result secondary to tissue infarction resulting in release of inflammatory mediators. We followed PRISMA guidelines and performed a systematic review of studies of PES following UAE from inception to October 2022. Our published protocol was prospectively registered. Our search yielded 54 results. We reviewed 22 full texts, and nine articles were included. Observational studies comprised 6/9 relevant studies, with 5/9 retrospective design. The rate of PES was documented in 5/8 studies (excluding case report) with a reported incidence ranging from 4-34.6%. Five of the nine studies studies postulated that the aetiological basis of PES is inflammatory related. Further research is necessary to advance our understanding of PES to define the biological basis of the syndrome with more certainty and gain a consensus on peri-procedure management to reduce incidence and improve patient outcomes.

Waldrop, J., et al. (2021). "Parenting Interventions and Secondary Outcomes Related to Maternal Mental Health: A Systematic Review." Maternal and Child Health Journal 25(6): 870-880.
	PURPOSE: Perinatal mood and anxiety disorders can have far reaching negative impact on both maternal mental health and child growth and development. Multimodal group parenting programs have been shown to improve maternal mental health symptoms however, they are often costly to provide and not accessible to many mothers, especially those mothers suffering from mental health symptoms. Therefore, the authors sought to answer the following question by undertaking a systematic review of the literature: are parenting interventions aimed at improving maternal-child interaction also a way to address mental health symptoms (i.e. depression, anxiety, stress) in mothers? METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. An online platform that supports the systematic review process and quality assessment according to Cochrane guidelines, Covidence, was used in conjunction with an adapted extraction tool to identify relevant studies and extract data for analysis. RESULTS: 11 articles were included in the qualitative synthesis. There was great heterogeneity between study interventions and measurement of outcomes for maternal mental health symptoms which precluded meta-analysis. CONCLUSION: Studies reviewed did not demonstrate consistent evidence to recommend that parenting interventions leads to improvement in maternal mental health symptoms for depression, anxiety or stress. However, there was evidence that participating in parenting programs does not worsen these symptoms and some encouraging evidence that alternative delivery methods, beyond face to face, could, with more research, lead to more financially feasible and sustainable models of delivery of these types of interventions in the future.

Wales University of, S. (2021). Symptom Monitoring and Menopausal Symptoms.
	No Results Available Behavioral: Symptom Monitoring Menopausal symptom changes via the Daily Record Keeping (DRK) form|Emotional outcomes via the Daily Record Keeping (DRK) form|Help seeking intentions|General Self Efficacy|Decision making efficacy|Health communication|Health Anxiety|Health Consciousness|Coping preference|Trait neuroticism Female Not Applicable 112 Other Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: None (Open Label)|Primary Purpose: Supportive Care 21059 October 14, 2021

Wali, S., et al. (2021). "Misoprostol for open myomectomy: a systematic review and meta-analysis of randomised control trials." BJOG : an international journal of obstetrics and gynaecology 128(3): 476-483.
	Background: Excessive blood loss is a significant risk of myomectomy with the potential need for hysterectomy.; Objective: To study the effectiveness of preoperative misoprostol compared with placebo at open myomectomy on intra- and postoperative outcomes.; Search Strategy: PubMed, Cochrane, Scopus, MEDLINE and EMBASE.; Selection Criteria: Randomised control studies of women undergoing open myomectomy for symptomatic fibroids who were given either misoprostol or placebo preoperatively.; Data Collection and Analysis: The revised Cochrane risk-of-bias tool for randomised trials was used to assess the risk of bias. Primary outcomes were blood loss, drop in haemoglobin and need for blood transfusion. Secondary outcomes were operative time, postoperative pyrexia and length of postoperative stay. Pooled effect sizes with corresponding 95% CI were calculated using random effects models. Data were analysed using two statistical models for statistical reliability.; Results: Eight studies were included with a total of 385 patients, of which 192 received misoprostol. Preoperative misoprostol was significantly associated with lower blood loss by -170.32 ml (95% CI -201.53 to -139.10), lower drop in haemoglobin by -0.48 g/dl (95% CI -0.65 to -0.31), reduced need for blood transfusion (odds ratio [OR] -0.48, 95% CI -0.65 to -0.31), and a reduction in operative time by -11.64 minutes (95% CI -15.73 to -7.54). There was no difference in postoperative pyrexia or length of postoperative stay.; Conclusion: Moderate- to high-quality studies have established that misoprostol minimises blood loss and need for blood transfusion at open myomectomy. This low-cost and readily available drug should be routinely administered prior to open myomectomy to improve clinical outcomes.; Tweetable Abstract: Use of misoprostol at open myomectomy reduces blood loss and need for blood transfusion with no impact on postoperative pyrexia. (© 2020 Royal College of Obstetricians and Gynaecologists.)

Walker, J., et al. (2022). "Long Term Survival of GOG 252 'Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/GOG Study' (021)." Gynecologic Oncology 166(Supplement 1): S16-S17.
	Objectives: The primary objective of this analysis of GOG 252 is to assess the overall survival of the subgroup of participants with metastatic epithelial ovarian cancer, with no more than microscopic residual disease, following their primary cytoreductive surgery followed by three chemotherapy regimens and bevacizumab. The results of the response to chemotherapy based on the CA-125 nadir are also included. Method(s): Patients were randomly assigned to six cycles of IV paclitaxel 80 mg/m2 weekly, with IV carboplatin AUC 6 on day 1 (IV carbo arm), versus IV paclitaxel 80 mg/m2 weekly, with IP carboplatin AUC 6 on day 1 (IP carbo arm) versus IV paclitaxel 135 mg/m2 IV on day 1 every three weeks, IP cisplatin 75 mg/m2 on day 2, and IP paclitaxel 60 mg/m2 on day 8 (IP Cisplatin arm). All participants received bevacizumab 15 mg/kg IV on day 1 every three weeks for cycles 2-22. CA-125 was drawn before each cycle of chemotherapy, and q3 months for the first two years and q6 months for the next three years and then annually. CT was performed postoperatively and before enrollment, and then every six months for five years and then annually. Result(s): A total of 1560 patients were enrolled of whom 900 (57.7%) had no more than microscopic residual disease as assessed by the surgeon. For this analysis, an excellent response to front line chemotherapy was to see a nadir of CA-125 < 10 before cycle 4. The median duration of follow up was 9.2 years. There were 573 with recurrent disease (63.7%) and 413 deaths (45.9%). There was no statistically significant difference in PFS between treatment groups (p=0.735, log-rank Chi square = 0.617 with 2 DF). The hazard of progression or death is relatively high for the first 3-4 years and then declines. The estimates of proportion of patients alive and recurrence-free at 10 years were 0.32, 0.33, and 0.32, respectively. The probability of living at least 10 years was 0.473, 0.467 and 0.470. The CA-125 nadir after cycle 1 and before cycle 4 of less than 10 was 53.5% 51.5%, and 34.4% in the three arms, respectively. The median PFS was 28.5 months for those with CA-125 nadir > 10 IU and 44.2 months for those less than or equal to 10 IU. The median survival for CA-125 nadir greater than 10 was 89 months. Conclusion(s): The overall survival of these patients was remarkable and was 108.6, 114.2, and 107.9 months, respectively. The proportional hazard model stratified by stage indicates the hazard of death is 38.5% higher among those with nadir values of CA-125?> 10. The quality of life was best in the intravenous arm.[Formula presented]Copyright © 2022 Elsevier Inc.

Walker, K. F., et al. (2020). "Pharmacological interventions for treating intrahepatic cholestasis of pregnancy." Cochrane Database of Systematic Reviews(7).
	- Background Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build‐up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. Objectives To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. Search methods For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov , the WHO International Clinical Trials Registry Platform ( ICTRP ) (13 December 2019), and reference lists of retrieved studies. Selection criteria Randomised or quasi‐randomised controlled trials, including cluster‐randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. Data collection and analysis The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. Main results We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo‐controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S‐adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) −7.64 points, 95% confidence interval (CI) −9.69 to −5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. Authors' conclusions When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low‐certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high‐quality trials of other interventions are needed in order to identify effective treatments for m ternal itc ing and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA). Plain language summary Interventions for treating intrahepatic cholestasis of pregnancy (ICP) What is the issue? A liver disorder arising during pregnancy, most often in the last three months, commonly causes itching (pruritus), which can be extremely distressing to the pregnant woman. Bile acids accumulate within the liver and the blood concentration of bile acids is raised, although not always apparent with the symptoms. The signs and symptoms often resolve spontaneously within the first few days after birth, and usually within four to six weeks. Although the condition is poorly understood, there is an association with preterm birth and stillbirth among women with the severest forms of the disease. Many treatments have been suggested. This review is an update of a review first published in 2001 and last updated in 2013. Why is this important? The itching can be disabling. Stillbirth and preterm birth are serious adverse outcomes which are important to prevent. What evidence did we find? We searched for evidence in December 2019, and identified 26 trials involving 2007 women. The trials assessed nine different interventions, but for most of them the trials were small and had a high risk of bias; we were therefore unable to draw firm conclusions. However, the most widely‐used treatment, ursodeoxycholic acid (UDCA), for which we identified seven trials (1008 women), included two trials at low risk of bias (755 women). There is now evidence that UDCA probably reduces itching (moderate‐certainty evidence). However, the size of the effect is small and for many pregnant women may not be worthwhile. The evidence for an effect of UCDA on stillbirth or fetal distress is unclear, mainly due to limitations in study design and imprecise results (very low‐certainty evidence). What does this mean? Although UDCA has not been shown to prevent the adverse outcomes of intrahepatic cholestasis of pregnancy, there is no other effective treatment for this condition, and there is a small reduction in maternal itch. More high‐quality trials of other treatments are needed in order to identify what is effective for maternal itching and to prevent adverse outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).

Wallace, S., et al. (2021). "Cost-effectiveness of transvaginal hysteropexy compared to vaginal hysterectomy with apical suspension for the treatment of pelvic organ prolapse: A 5-year markov model." Neurourology and Urodynamics 40(SUPPL 1): S65-S67.
	Objective: Studies suggest that transvaginal hysteropexy (HP) has equivalent 5-year efficacy compared to traditional vaginal hysterectomy (VH) with apical suspension (sacrospinous ligament fixation (SS) or uterosacral ligament suspension (US)), but costs at 5 years between these approaches have not been compared. Our objective was to perform a cost-effectiveness analysis of transvaginal HP versus VH with apical suspension for the treatment of uterine prolapse. Method(s): We used TreeAge Pro software to construct a decision model tree comparing the costeffectiveness of four surgical options: transvaginal HP with SS (HP-SS), transvaginal HP with US (HP-US), VH with SS (VH-SS) and VH with US (VH-US). Using a Markov model, we modeled a population of healthy women undergoing surgery over a 5-year time horizon. We used data from a recent randomized controlled trial to model prolapse recurrence, retreatment and complications. Costs, probabilities, and utilities were gathered from Medicare reimbursement data, published literature and the Stanford Hospital billings department (Table 1). Cost-effectiveness was defined as an incremental costeffectiveness ratio (ICER) < $100,000/QALY. Result(s): In the base case scenario, HP strategies were the optimal cost-effective strategies. The surgical strategy with the lowest cost per patient was HP-SS costing $42,287.81 with Total QALY 4.13 for HP-SS. The incremental HP-US cost compared to HP-SS was $1,065.37 with incremental QAL of +0.07. VH-SS and VH-US were dominated strategies with higher incremental costs ($7,642.20 and $8,706.08), and lower QALYS (-0.06 and-0.02). Tornado plots showed that the variables that most influenced CEA results were the cost of the four surgical strategies and the probability of complications following HP. VH strategies were cost-effective when cost of HP-SS was > $47,500 and HP-US was > $51,800. They were also cost-effective when the probability of complications after HP-SS was >30% and the probability of complications after HS-US was > 32%. At all probabilities of prolapse recurrence after HS and VH and at all probabilities of repeat surgery after HS and VH surgical failure, HS surgeries remained cost-effective strategies. Conclusion(s): Uterine-preserving hysteropexies are cost-effective surgical strategies for the treatment of uterine prolapse over a 5-year time horizon, even if we assume higher rates of prolapse recurrence and repeat POP surgery.

Wallin, E. (2021). "Oncologic and functional outcomes after robot-assisted radical hysterectomy for cervical cancer." Dissertation Abstracts International: Section B: The Sciences and Engineering 82(9-B): No-Specified.
	Background: Cervical cancer is the fourth most common cancer in women worldwide, but the incidence has rapidly declined in developed countries after the introduction of structured screening programs. This disease is caused by persistent HPV infection commonly acquired in adolescence, thereby affecting young women. In countries with established screening programs, early detection has resulted in favorable prognosis. Surgical treatment is the main treatment for early-stage disease and radical hysterectomy (RH) cures more than 90% of those afflicted. However, this treatment is associated with considerable morbidity and impaired quality of life (QoL). In 2005, robot-assisted laparoscopic radical hysterectomy (RRH), was introduced and subsequently implemented in Sweden. The perceived benefits of minimally invasive surgery (MIS), and of RRH in particular, have not been confirmed. It is therefore imperative to assess the efficacy and safety of this surgical technique, as well as short- and long-term adverse effects, particularly since long-term survival is expected. Aims: The overall aim was to investigate the oncologic safety of RRH. Secondary aims included assessment of surgical outcomes, health care costs and impact on QoL, bladder, bowel, sexual and lymphatic function after RRH. Methods: To assess the oncologic and surgical outcomes, two population-based studies were performed (Studies I and II). Study I included 304 women who underwent RH stage IA1-IIA during 2006-2015 at Karolinska University Hospital (KUH). Surgical and oncologic outcomes, as well as the costs of RRH and open radical hysterectomy (ORH) were compared. Study II, a nationwide cohort study, assessed overall and disease-free survival after RRH and ORH in 864 women with stage IA1-IB1 disease. The functional impact of RRH was investigated in two prospective clinical studies (Studies III and IV) with one-year follow-up. In Study III, 26 women undergoing RRH filled in a questionnaire regarding psychological well-being and sexual, bowel, bladder, and lymphatic function. In addition, postoperative ovarian function was measured by change in sex hormones. In Study IV, 27 patient-reported outcomes after RRH were assessed using two validated questionnaires concerning bladder function and its impact on QoL. Outcomes were determined objectively by urodynamics and quantification of ablated autonomic nerves. Results: In the regional study (Study I), RRH was associated with an increased risk of recurrence (HR 2.13; 95% CI, 1.06-4.26). The postoperative complication rates (37%) and costs were similar, but the hospital stay was shorter than following ORH. The nationwide study (Study II) showed no statistical difference between RRH and ORH with respect to 5-year OS (HR 1.00; 95% CI, 0.50-2.01) and DFS (HR 1.08; 95% CI, 0.66-1.78). Study III demonstrated that RRH had a minor effect on sexual function, as well as bowel function. However, bladder impairment and lymphedema remained the main dysfunctions associated with RRH for cervical cancer (Studies III and IV). No correlation between the number of autonomous nerves ablated and functional outcomes was observed. In general, postoperative urinary symptoms diminished over time, but persisted in a substantial proportion of the women and may impair QoL. Conclusions: RRH appears to be safe once surgical proficiency is achieved. Prospective trials are needed to ensure the safety of RRH for cervical cancer. RRH was associated with less perioperative morbidity, and health care costs were similar to those of ORH. RRH seems to have only minor effects on sexual function, though bladder dysfunction remains a significant sequele. The cause of functional impairment after RRH is multifactorial and cannot be explained by nerve ablation alone. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Wallington, D. G. and E. B. Holliday (2021). "Preparing patients for sexual dysfunction after radiation for anorectal cancers: a systematic review." Practical radiation oncology 11(3): 193-201.
	PURPOSE: Successful multimodality treatment of anorectal cancers has led to increased numbers of survivors who experience permanent, life-changing side effects of treatment. Little is known about sexual dysfunction (SD) in this population. The etiology of SD after anorectal cancer treatment is complex and multifactorial. However, pelvic radiation plays a significant negative role in anatomic, hormonal and physiologic aspects of sexual function. METHODS AND MATERIALS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Information was organized by key concepts useful for patient education including: 1.) rates of SD after pelvic radiation for rectal cancer 2.) rates of SD after pelvic radiation for anal cancer 3.) mechanisms of SD and methods to reduce rates of SD 4.) issues and opportunities related to patient education and discussion of SD after pelvic radiation. RESULTS: SD after pelvic radiation for anorectal cancers is common in both men and women. Higher radiation doses may increase the risk for vaginal stenosis; however, it is unclear whether there are similar dose/volume relationships for men. Vaginal dilators and advanced radiation techniques can reduce the radiation dose to sexual organs at risk. Improvement is needed regarding counseling and education of patients regarding SD. CONCLUSIONS: This review provides information from previously published studies that clinicians may use in their discussions with patients embarking on pelvic radiation for anorectal cancers. More modern, standardized and complete data are needed to quantify the risk of SD after treatment. Some methods of sexual toxicity reduction have been studied, but further study into interventions aimed at treating post-radiation sexual function are needed.

Walsh Gregory, S., et al. (2023). "The comparative effect of exercise interventions on balance in perimenopausal and early postmenopausal women: A systematic review and network meta-analysis of randomised, controlled trials." Maturitas 175: 107790.
	In addition to a range of physiological and psychological symptoms, menopause causes a decrement to balance performance and risk of falls. This review aimed to determine the effects of exercise interventions on balance in perimenopausal and early postmenopausal women. Web of Science, PubMed, CINAHL, SPORTDiscus and Cochrane Central Register of Controlled Trials databases were searched. Randomised, controlled trials of exercise interventions in perimenopausal or early postmenopausal populations with an average age of 65 years or younger reporting balance measures were included. Risk of bias was assessed using Cochrane RoB 2. A random effects model network meta-analysis was performed to assess the effect of exercise on balance. Standardised mean differences with 95 % confidence intervals were used as the measure of effect. Twenty-six studies were included after screening. Network meta-analyses were conducted for 5 balance variables. Whole-body vibration (standardised mean difference: 2.25, confidence interval: 0.08; 4.43), balance (standardised mean difference: 1.84, confidence interval: 0.15; 3.53), balance + nutrition (standardised mean difference: 3.81, confidence interval: 1.57; 6.05) and resistance (standardised mean difference: 1.43, confidence interval: 0.41; 2.46) exercise improved Berg balance scale performance. Resistance + aerobic + balance exercise improved one-leg stance (standardised mean difference: 0.80, confidence interval: 0.39; 1.22) and whole-body vibration improved anterior-posterior (standardised mean difference: -0.89, confidence interval: -1.48; -0.31), medio-lateral (standardised mean difference: -0.58, confidence interval: -1.15; -0.01) postural sway and falls indices (standardised mean difference: -0.75, confidence interval: -1.45; -0.04). Exercise improved all balance measures and should be considered as an adjunct therapy in perimenopausal and postmenopausal women. Whole-body vibration was most frequently the highest ranked intervention; resistance and balance training also improved balance.; Competing Interests: Declaration of competing interest The authors declare that they have no competing interest. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Walter, A., et al. (2021). "Gemogenovatucel-T (Vigil) maintenance immunotherapy: 3-year survival benefit in homologous recombination proficient (HRP) ovarian cancer." Gynecologic Oncology 163(3): 459‐464.
	Objective: Previously, Vigil demonstrated clinical benefit to prolong relapse free and overall survival in the BRCA wild‐type (BRCA‐wt), homologous recombination proficient (HRP) patient population. Here we provide long term follow up of 3 years in the HRP patient population enrolled in the Phase 2b VITAL study. Methods: HRP patients treated with Vigil (n = 25) or placebo (n = 20) who were enrolled in the Phase 2b, double‐blind, placebo‐controlled (VITAL study, NCT02346747) were followed for safety, OS and RFS. OS and RFS from time of randomization (immediately prior to maintenance therapy) and from debulking tissue procurement time points were analyzed by Kaplan‐Meier (KM) and restricted mean survival time (RMST) analysis. Results: OS for Vigil treated patients at 3 years has not yet reached median OS time point (95% CI 41.6 months to not achieved) compared to 26.9 (95% CI 17.4 months to not achieved) in placebo treated patients (HR 0.417 p = 0.020). Three year RFS also showed benefit to Vigil (stratified HR 0.405, p = 0.011) and no long term toxicity to Vigil was observed. Three year OS for Vigil of 70% vs. 40% for placebo from time of randomization was observed (p = 0.019). RMST analysis was also significant for OS (45.7 vs. 32.8 months, p = 0.008) and RFS (p = 0.025). Conclusion: In conclusion, results suggest durable activity of Vigil on RFS and OS and support further evaluation of Vigil in HRP ovarian cancer.

Walter, J. R., et al. (2021). "COST-EFFECTIVENESS ANALYSIS OF THE ACTIVE TREATMENT OR NO TREATMENT (ACT OR NOT) RANDOMIZED CONTROLLED TRIAL OF THE OPTIMAL MANAGEMENT OF PERSISTENT PREGNANCIES OF UNKNOWN LOCATION." Fertility and Sterility 116(3): e77‐e78.
	Objective: Pregnancies of unknown location (PUL) account for ∼10% of all pregnancies and optimal, cost‐conscious management of persistent PULs remains an area of continued controversy. Materials and Methods: We performed a planned, prospective, economic evaluation concurrent with the multicenter ACT or NOT trial of 255 women with abnormally trending human chorionic gonadotropin levels consistent with a nonviable gestation without ultrasonographic evidence of an intrauterine or extrauterine pregnancy, conducted from 7/25/2014 to 6/4/2019. Participants were randomized 1:1:1 to expectant management (EXP), uterine evacuation (UE) with methotrexate if indicated, or two doses of methotrexate (MTX), stratified by site. Analysis was performed based on actual treatment received given high rate of crossover. A within‐trial analysis was performed from the healthcare sector perspective with a 6‐week time horizon. Costs were estimated from actual healthcare utilization, in 2018 USD. Health care unit costs were assigned from national Medicare reimbursement rates or published prices. UE occurred primarily by manual vacuum aspiration in clinic; dilation and evacuation was assumed evenly performed in clinic and a surgical center. Salpingectomies were laparoscopic outpatient procedures. Effectiveness was measured in quality‐adjusted life‐year (QALY) and rate of salpingectomy. The primary outcome was incremental cost‐effectiveness ratio (ICER) of cost/QALY gained; cost/1% reduction in salpingectomy was a secondary outcome. Results: MTX had the lowest mean cost, of $875, followed by EXP $1085, and UE $1902 (p=0.001). EXP had the highest QALY of all treatment arms (0.0784) followed by UE (0.0769) and MTX (0.0725) (p=0.13). There was a higher rate of salpingectomy in the EXP arm compared to MTX (9.4% vs 1.2%; p=0.02). EXP was cost effective compared to MTX with an ICER of $35,610/QALY gained (95% CI, ‐$425,247.40 to $501,594.30). EXP dominated UE. Cost‐effectiveness acceptability curve analysis demonstrated EXP was cost‐effective 89% of the time compared to MTX at the generally accepted maximum willingness‐to‐pay threshold of $150,000/QALY gained. The incremental cost per 1% reduction in salpingectomy rate was $26 favoring MTX over EXP and $633 favoring UE over EXP. Conclusions: This study demonstrated management of PULs with EXP was cost‐effective when compared to MTX and UE but had the highest rate of salpingectomy. Impact Statement: Treatment of persistent PULs with EXP is a cost‐effective approach compared to MTX and UE. [Formula presented]

Wan, Y. L., et al. (2021). "Prognostic models for predicting recurrence and survival in women with endometrial cancer." Cochrane Database of Systematic Reviews 2021(6): CD014625.
	Objectives: This is a protocol for a Cochrane Review (prognosis). The objectives are as follows:. To review all prognostic models that combine two or more clinical, histological or molecular variables, or a combination of these variables, to provide an individualised assessment of risk of recurrence or death from disease and evaluate their performance to predict these outcomes in people undergoing curative treatment for endometrial cancer.Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Wan, Z., et al. (2022). "Perturbations in Gut Microbiota Composition in Patients with Polycystic Ovary Syndrome: A Review and Meta-analysis."
	
Wang, C., et al. (2020). "Guizhi Fuling wan for chronic pelvic inflammatory disease protocol: A protocol for systematic review and meta analysis." Medicine 99(51): e23549.
	Background: Chronic pelvic inflammatory disease (CPID) is one of common diseases of department of gynaecology, point to female inside genital and circumferential organization to suffer from infection of all sorts of pathogenic bacteria and cause chronic inflammation sex disease, also cause one of main factors of infertile of female of childbearing age period. Due to its insidious onset, it is not easy to find out in the early stage. Therefore, it is difficult to obtain satisfactory curative effect by taking routine treatment with antibiotics. In recent years, TCM has made great strides in the treatment of chronic pelvic inflammation, a number of clinical studies have shown that Guizhi Fuling wan combined with antibiotics can significantly improve the clinical symptoms and enhance the therapeutic effect. Therefore, we intend to conduct a system review and meta-analysis to further clarify the effectiveness and safety of GZFLW for CPID.; Methods: We will search each database from the built-in until September2020.The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieval clinical registration tests and grey literatures. This study only screens the clinical randomized controlled trials (RCTs) about GZFLW for CPID to assess its efficacy and safety. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on whether or not heterogeneity exists. The clinical efficacy, pelvic effusion and mass were evaluated as the main outcomes. The serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor (TNF)-α, erythrocyte sedimentation rate (ESR), erythrocyte specific volume was secondary outcomes. Finally, meta-analysis was conducted by RevMan software version 5.3.; Results: This study will provide high-quality evidence for treatment of CPID with GZFLW in terms of effectiveness and safety.; Conclusion: This systematic review aims to provide new options for GZFLW treatment of CPID in terms of its efficacy and safety.; Ethics and Dissemination: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.; Osf Registration Number: DOI 10.17605 / OSF.IO / R9NVT.; Competing Interests: The authors have no conflicts of interests to disclose. (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Wang, C. and J. Li (2021). "Haematologic toxicities with PARP inhibitors in cancer patients: an up-to-date meta-analysis of 29 randomized controlled trials." Journal of Clinical Pharmacy and Therapeutics 46(3): 571-584.
	What is known and objective: Poly ADP-ribose polymerase (PARP) inhibitors have emerged as one of the most exciting new treatments for patients with certain types of cancer. Haematologic toxicities are common adverse events (AEs) for all PARP inhibitors. We conducted a meta-analysis to fully investigate the haematologic toxicities of PARP inhibitors in cancer patients. Study design: PubMed/Medline and Embase were searched for articles published till September 2020. The relevant randomized controlled trials (RCTs) in cancer patients treated with PARP inhibitors were retrieved, and the systematic evaluation was performed. Result(s): Twenty-nine RCTs and 9247 patients were included. The current meta-analysis suggests that the use of PARP inhibitors significantly increases the risk of all-grade anaemia (RR, 2.32; 95% CI, 1.78-3.01; p < 0.00001), neutropenia (RR, 1.69; 95% CI, 1.38-2.07; p < 0.00001) and thrombocytopenia (RR, 2.54; 95% CI, 1.87-3.45; p < 0.00001). The use of these agents also significantly increased the risk of high-grade anaemia (RR, 3.06; 95% CI, 2.11-4.43; p < 0.00001), neutropenia (RR, 1.66; 95% CI, 1.33-2.07; p < 0.00001) and thrombocytopenia (RR, 2.76; 95% CI, 1.83-4.16; p < 0.00001). Anaemia was the most common haematologic toxicity, and all the five included PARP inhibitors were associated with a significant increased risk of anaemia. Combination treatment may reduce the risk of anaemia and thrombocytopenia compared to those receiving PARP inhibitor monotherapy. What is new and conclusion: The available data suggested that the use of PARP inhibitors was associated with a significantly increased risk of haematologic toxicities.Copyright © 2021 John Wiley & Sons Ltd

Wang, C., et al. (2021). "Colonic endometriosis diagnosed by endoscopic piecemeal mucosal resection: A case report and literature review." World Chin. J. Dig. 29(9): 496-500.
	
Wang, C., et al. (2022). "Network Meta-analysis of Chinese patent medicine combined with mifepristone in treatment of uterine fibroid." Chinese Traditional and Herbal Drugs 53(21): 6820-6831.
	Objective To evaluate the efficacy and safety of different Chinese patent medicines combined with mifepristone in treatment of uterine fibroid by network Meta-analysis. Methods The randomized controlled trials (RCTs) of Chinese patent medicine combined with mifepristone in the treatment of uterine fibroid were searched by computer from Scopus, PubMed, Embase, Cochrane Library, Web of Science, Wanfang, VIP, China Biology Medicine Disc (CBM) and China National Knowledge Internet (CNKI) databases. The retrieval period was from the establishment of each database to March 2022. After two evaluators independently screened the literature, extracted the data and evaluated the risk of bias in the included study, network Meta-analysis and ranking diagram were performed by ADDIS 1.16.8 software, and used stata14.0 software to draw the funnel plot. Results A total of 43 studies with 4354 cases were included in the study. It involved seven kinds of Chinese patent medicines, including Gongliuning Capsules (), Gongliuxiao Capsules (), Gongliuqing Capsules (), Guizhi Fuling Pills (Capsules) [ ( )], Xuefu Zhuyu Capsules (Oral Liquids) [ ( )], Danbie Capsules ( ) and Xiaojin Pills (Capsules) [ ( )]. The results of network Meta-analysis showed that in terms of total clinical effective rate, reducing uterine fibroid volume and improving estradiol level: Xuefu Zhuyu Capsules (Oral Liquids) + mifepristone had the best effect; In terms of reducing the size of the uterus: Guizhi Fuling Pills (Capsules) + mifepristone had the best effect; In terms of increasing the level of follicle stimulating hormone: Danbie Capsules + mifepristone had the best effect; In terms of increasing the levels of luteinizing hormone and progesterone: Gongliuning Capsules + mifepristone had the best effect. The adverse reactions of Xuefu Zhuyu Capsules (Oral Liquids) + mifepristone were the least during medication. Conclusion Seven Chinese patent medicines combined with mifepristone has good clinical efficacy in treatment of uterine fibroid, among which the best results were obtained with Xuefu Zhuyu Capsules (Oral Liquids) + mifepristone. Different patients can choose different medications according to different needs, but the number of studies and sample size were too small, large sample size studies were still needed to confirm.Copyright © 2022 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Wang, G., et al. (2022). "YOGA'S THERAPEUTIC EFFECT ON PERINATAL DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS." Psychiatria Danubina 34(2): 195-204.
	Introduction: In recent years, the incidence of perinatal depression in female population is very high. Perinatal depression has adverse effects on the physical and mental health of mothers and children. However, according to current researches, Yoga has been considered as an effective exercise that can help pregnant women to regulate their emotions. Thus, this review reports the effectiveness of yoga on perinatal depression. Method(s): We reviewed all of the relevant RCT (Randomized Control Trial, RCT) studies published until June 2021 from the major open-access databases. Result(s): 12 RCTs were selected and included in this study, and the total number of people included in the analysis in the combined study was 594. The level of depression and anxiety of participants was evaluated using detailed and recognized scale. Compared with the control group, the yoga intervention group indicates a statistically significant decrease in depression levels (SMD (Standardised Mean Difference, SMD), -2.31; 95% CI, -3.67 to -0.96; P=0.139) and anxiety (SMD, -4.75; 95% CI, -8.3 to -1.19; P=0.002). In addition, we also conducted a subgroup analysis according to the type of population. The subgroup analysis successfully reduced the level of heterogeneity and the results indicated that the difference in population types in the combined analysis leads to the higher heterogeneity. The SMD value for healthy women is -2.3 (95% CI, -4.83 to 0.23) and for depressed women is -9.02 (95% CI, -11.42 to -6.62). Finally, the meta-analysis results of the self-control group prove that yoga can reduce the depression scores (SMD, 5.23; 95% CI, 1.90 to 8.56; P=0.049) compared with baseline. Conclusion(s): Yoga can effectively relieve symptoms of depression and anxiety in the perinatal period, which can be used as an auxiliary treatment option clinically.Copyright © 2022 Medicinska Naklada Zagreb. All rights reserved.

Wang, G., et al. (2023). "Correction to: Effects of mindfulness-based intervention for women with infertility: A systematic review and meta-analysis." Archives of Women's Mental Health 26(6): 869.
	Reports an error in "Effects of mindfulness-based intervention for women with infertility: A systematic review and meta-analysis" by Guangpeng Wang, Xueyan Liu and Jun Lei (Archives of Women's Mental Health, 2023[Apr], Vol 26[2], 245-258). A discrepancy has been identified in the author affiliations for the published article. The correct author affiliations are present in the erratum. (The following abstract of the original article appeared in record 2023-59422-001). This review aimed to examine the effects of mindfulness-based interventions on physical and psychological outcomes in women with infertility. Studies were included if participants were women diagnosed with infertility, were over the age of 18, and the design was a randomized controlled trial of a mindfulness-based intervention program. Two independent reviewers undertook eligibility screening, data extraction, and methodological quality assessment. We used RevMan software version 5.4 (The Cochrane Collaboration) to conduct the meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was followed. Ten articles were finally included in the current meta-analysis. The results of the meta-analysis revealed large, significant effects of mindfulness-based interventions that can effectively reduce depression[SMD = -1.28, 95% CI (-1.95, -0.60), P < 0.0001], anxiety [SMD = -0.89, 95% CI (-1.26, -0.51), P < 0.00001] symptoms, and improve five domains of health-related quality of life (physical function [MD = 9.47, 95% CI (4.33, 14.61), P = 0.0003], general health [MD = 15.77, 95% CI (7.62, 23.92), P = 0.0002], vitality [MD = 14.85, 95% CI (4.95, 24.74), P = 0.003], role-physical [MD = 22.44, 95% CI (14.97, 29.91), P < 0.00001] and social function [MD = 8.27, 95% CI (3.56, 12.97), P = 0.0006)] in women with infertility. The current meta-analysis results revealed that mindfulness-based interventions could effectively reduce depression and anxiety symptoms and improve health-related quality of life in women with infertility. Future rigorously designed, high-quality research is required to demonstrate whether mindfulness-based intervention programs can effectively reduce perceived stress and BM (PsycInfo Database Record (c) 2024 APA, all rights reserved)

Wang, H., et al. (2021). "Adverse Pregnancy Outcomes Following Exposure to Biologics in Women With Crohn's Disease: A Systematic Review and Meta-Analysis." Frontiers in Medicine 8: 753088.
	Crohn's disease is a chronic disease, which commonly affects women during their reproductive years. Poorly treated Crohn's disease is associated with adverse pregnancy outcomes. Biologics, a group of therapeutic drugs targeting inflammatory mediators including anti-TNF, anti-integrins and anti-interleukins, are increasingly used in pregnant women with Crohn's disease, exposing both the women and their fetuses to treatment-related complications. At present, it is unclear which biologics are more superior. This study performed a systematic review and meta-analysis to assess the risk of adverse pregnancy outcomes in women with Crohn's disease after exposure to biologics. Bibliographic databases were searched from inception to May 2021. The outcomes of interest were preterm delivery, low birth weight, spontaneous abortion, and congenital abnormalities. A total of 11 studies comprised of 1,875 pregnancies among women with Crohn's disease were included. Of these, 1,162 received biologics and 713 received non-biologic therapy. During the remission phase of the disease, the use of biological therapy increased the risk of adverse pregnancy outcomes, of which anti-integrins were associated with a higher incidence of adverse pregnancy outcomes than anti-TNF and anti-interleukins. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020191275.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Wang, Chen, Hu and Shen.)

Wang, H., et al. (2019). "The efficacy and safety of moxibustion for primary dysmenorrhea: A systematic review protocol." Medicine 98(48): e18133.
	Background: Primary dysmenorrhea (PDM) is one of the most prevalent gynecological diseases in women of childbearing age. The major medications treating PDM usually make sense and side effects, while moxibustion is known as a safe and effective treatment for PDM. This review aims to systematically evaluate the effect and safety of moxibustion for treating PDM.; Methods: We will search all randomized controlled trials for moxibustion therapy on PDM, electronically and manually, regardless of publication status, till October 31, 2019. Online databases include the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; China National Knowledge Infrastructure; Chinese Biomedical Literature Database; Chinese Scientific Journal Database (VIP database); and Wan-Fang Database. Two reviewers will search these databases, select data and measure the quality of studies independently. The methodological quality will be assessed by the Cochrane Reviewer's Handbook 6.0. The primary outcomes include clinical efficacy and visual analog scale, and the secondary outcomes include adverse events and quality of life. Four reviewers will independently extract the data and assess the qualities of the studies. Statistical analysis will be conducted with R package for each outcome. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 reviewers.; Results: This study will provide a comprehensive review of the available evidence for the treatment of moxibustion with PDM.; Conclusion: The conclusion of our study will provide updated evidence to judge whether moxibustion is an effective and safe intervention for patients with PDM.; Prospero Registration Number: CRD42019129993.

Wang, H., et al. (2023). "Efficacy and safety of Chaihu class prescriptions in the treatment of perimenopausal anxiety: a Meta-analysis."
	
Wang, H., et al. (2023). "The Role of Acupuncture and Its Related Mechanism in Treating Chronic Prostatitis/Chronic Pelvic Pain Syndrome." International Journal of General Medicine 16: 4039-4050.
	Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, and its prevalence has been increasing, causing serious urogenital problems in men. Several targeted oral drug therapies exist to treat the pelvic pain experienced in this disease. However, these therapies may have potential adverse effects, and due to the unique location of the prostate, delivery of medications to the target lesion is difficult. Consequently, many patients seek alternative therapies. Acupuncture is a well-established treatment method in traditional Chinese medicine that can improve CP/CPPS symptoms and reduce pain. However, previous systematic reviews overlooked the significance of the characteristics and mechanisms of acupuncture therapy. This study aimed to summarize the characteristics and benefits of acupuncture therapy for CP/CPPS based on relevant literature and predict and analyze its related mechanisms.; Competing Interests: The authors report no conflicts of interest in this work. (© 2023 Wang et al.)

Wang, H. K., et al. (2021). "Oral Chinese patent medicine containing Epimedium in treatment of postmenopausal osteoporosis: A bayesian network Meta-analysis." Chinese Traditional and Herbal Drugs 52(20): 6309-6322.
	Objective: To systematically evaluate the efficacy and safety of oral Chinese patent medicine of Epimedium in the treatment of postmenopausal osteoporosis (PMOP). Method(s): The Cochrane Library, PubMed, EMbase, CNKI, CBM, Wanfang and VIP databases were electronically retrieved to gather randomized controlled trials (RCT) of oral Chinese patent medicine of Epimedium in treatment of PMOP from their inception to Apr. 2021. After two researchers independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed, bayesian network Meta-analysis was performed by GeMTC0.14.3 and Stata15.1. Result(s): A total of 49 RCTs were included, involving 18 drug regimens of nine Chinese patent medicines. Network Meta-analysis showed that 1in terms of improving the total effective rate, the top three therapeutic regimens were Xianling Gubao (XLGB, ) +conventional treatment of Western medicine (Con)>Bushen/Yishen Jiangu[JG, ()] +Con>Modified Erxian (EX) +Con; 2in terms of increasing the level of bone mineral density (BMD), the top three therapeutic regimens: Gushukang (GSK, ) +Con>JG+Con>MIGU () +Con; 3in terms of reducing the visual analogue scale (VAS) score, the top three therapeutic regimens: Jinwu Gutong (JWGT, ) +Con>EX+Con>XLGB+Con; in terms of increasing serum calcium level, the top three therapeutic regimens: JG>XLGB+Con>GSK; 5in terms of increasing serum phosphorus level, the top three therapeutic regimens: Bushen Zhuanggu (BSZG, )>GSK+Con>GSK; GSK may have the lowest incidence of adverse reactions. Conclusion(s): In terms of therapeutic effectiveness of PMOP, each Chinese patent medicine has its own unique advantages; In terms of safety, Chinese patent medicines are generally safe and GSK may have the highest safety. Due to the quality and methodological limitations of the included studies, more highquality RCTs are needed to validate the conclusions.Copyright © 2021, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Wang, J., et al. (2022). "Levonorgestrel-releasing intrauterine system vs. systemic medication or blank control for women with dysmenorrhea: Systematic review and meta-analysis of randomized controlled trials." Frontiers in Global Women's Health 3: 1013921.
	Aims: To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with systemic medication or blank control in the treatment of dysmenorrhea.; Methods: PubMed, EMBASE, the China National Knowledge Infrastructure (CNKI) and Wanfang Data were searched to collect randomized controlled trials (RCTs) comparing LNG-IUS with systemic medication or blank control among women diagnosed with primary dysmenorrhea or secondary dysmenorrhea (adenomyosis or endometriosis) from inception to 2020.04. Der Simonian-Laird random-effect model was used to pool data.; Results: Seventy-one RCTs (6551 patients) were included. Overall bias risk was medium. Sixty-two articles enrolled patients with adenomyosis; LNG-IUS significantly reduced the visual analogue scale (VAS) score compared with the systemic medication group among adenomyosis women at 3 months (standardized mean difference (SMD) = -0.81, 95% confidence interval (CI) -1.22 to -0.40); 6 months (SMD = -1.25, 95%CI: -1.58 to -0.92); 9 months (SMD = -1.23, 95%CI: -1.63 to -0.83); 12 months (SMD = -1.66, 95%CI: -2.14 to -1.18). No difference was found in the incidence of irregular vaginal bleeding (16 RCTs; RR = 0.91, 95%CI: 0.62-1.33, P = 0.63, I 2 = 4%) and other adverse outcomes. Sensitivity analysis regarding randomization methods was robust. Nine RCTs enrolled endometriosis women. Pooling results showed no significant difference between LNG-IUS and systemic medication treatment in terms of VAS at 6 months (SMD = -0.27, 95% CI: -0.97-0.43). Moreover, LNG-IUS was associated with higher risk of irregular vaginal bleeding (26.8% vs. 0).; Conclusions: LNG-IUS was associated with a reduced severity of dysmenorrhea compared with systemic medication; it was also beneficial for better control of menstrual blood loss and fewer adverse outcomes. Owing to small sample sizes, further well-designed RCTs are warranted to confirm these findings and long-term effects of LNG-IUS in the treatment of dysmenorrhea.; Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2022 Wang, Deng, Li, Dai, Sun.)

Wang, J., et al. (2023). "Effects of clean intermittent catheterization and transurethral indwelling catheterization on the management of urinary retention after gynecological surgery: a systematic review and meta-analysis." Translational Andrology and Urology 12(5): 744-760.
	Background: Urinary retention is a common complication after gynecological surgery. Clean intermittent catheterization has been reported to have a lower incidence of urinary tract infections compared to transurethral indwelling catheterization. This study conducted a systematic review of randomized controlled trials (RCTs) to compare the effects of these two catheterization techniques after gynecological surgery.; Methods: We searched PubMed, EMBASE, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journal Database (VIP) for 227 articles comparing the effects of the above two catheterization methods on urinary tract infections and urethral function after gynecological surgery up to November 2022. Subsequently, the Cochrane tool for assessing the risk of bias was employed to assess the quality of the included literature. Meta-analysis was performed using Stata software, and the appropriate models were adopted to pool the effect sizes.; Results: A total of 19 articles involving 1,823 patients were included. The results showed that clean intermittent catheterization could greatly minimize the risk of urinary tract infections [relative risk (RR) =0.24, 95% confidence interval (CI): 0.20 to 0.28], improve the recovery of bladder function (RR =1.51, 95% CI: 1.32 to 1.72), reduce residual urine volume (mL) [weighted mean difference (WMD) = -82.64, 95% CI: -108.32 to -56.96], and shorten the duration of catheter maintenance (days) (WMD =-3.14, 95% CI: -4.98 to -1.30) compared with indwelling catheterization. Subgroup and regression analyses revealed that clean intermittent catheterization could achieve a more favorable therapeutic effect in patients receiving cervical cancer surgeries than those receiving other conventional gynecological procedures.; Conclusions: Clean intermittent catheterization can lower the incidence of urinary tract infections, reduce residual urine volume, shorten the duration of catheter maintenance, and improve bladder function recovery. Thus, it may be more effective in patients undergoing radical cervical cancer resection.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-220/coif). The authors have no conflicts of interest to declare. (2023 Translational Andrology and Urology. All rights reserved.)

Wang, J., et al. (2023). "Does Omega-3 Fatty Acid Supplementation Have Favorable Effects on the Lipid Profile in Postmenopausal Women? A Systematic Review and Dose-response Meta-analysis of Randomized Controlled Trials." Clinical therapeutics 45(1): e74-e87.
	Purpose: Menopause is associated with disturbances in the metabolism of lipids. Moreover, during the postmenopausal period, female subjects are more prone to develop dyslipidemia. Omega-3 fatty acids, which exert cardioprotective, anti-inflammatory, and lipid-lowering actions, are commonly recommended in postmenopausal women. However, their effect on serum lipids in this population remains unclear. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify this research question.; Methods: We systematically searched the Web of Science, Scopus, PubMed/MEDLINE, and EMBASE databases from their inception until January 3, 2022. The DerSimonian and Laird random-effects model was used to combine effect sizes.; Findings: Omega-3 fatty acid supplementation resulted in a decrease in triglyceride concentrations (weighted mean difference [WMD], -17.8 mg/dL; 95% CI, -26 to -9.6; P < 0.001), particularly in the RCTs that lasted ≤16 weeks (WMD, -18.6 mg/dL), when the baseline triglyceride concentrations were ≥150 mg/dL (WMD, -22.8 mg/dL), in individuals with a body mass index ≥30 kg/m 2 (WMD, -19.3 mg/dL), and when the dose of omega-3 fatty acids was ≥1 g/d (WMD, -21.10 mg/dL). LDL-C (WMD, 4.1 mg/dL; 95% CI, 1.80 to 6.36; P < 0.001) and HDL-C (WMD, 2.1 mg/dL; 95% CI, 0.97 to 3.2; P < 0.001) values increased. Total cholesterol levels (WMD, -0.15 mg/dL; 95% CI, -4 to 3.74; P = 0.94) remained unchanged after administration of omega-3 fatty acids.; Implications: In postmenopausal women, supplementation with omega-3 fatty acids resulted in a significant reduction in triglyceride concentrations and a modest elevation in HDL-C and LDL-C levels, whereas this intervention did not affect total cholesterol values. (Copyright © 2022 Elsevier Inc. All rights reserved.)

Wang, J., et al. (2020). "A Meta-Analysis of Robotic Surgery in Endometrial Cancer: Comparison with Laparoscopy and Laparotomy." Disease markers 2020: 2503753.
	Background: The safety and effectiveness of robotic surgery are evaluated by comparing perioperative outcomes with laparoscopy and laparotomy in endometrial cancer.; Method: PubMed, MEDLINE, Embase, Cochrane, and other databases were searched for eligible studies up to April 2019. Studies that compared robotic surgery with laparoscopy or laparotomy in surgical staging of endometrial cancer were included. The pooled odds ratio and weighted mean difference were calculated using a random-effects or a fixed-effects model to summarize the results.; Results: Twenty-seven articles were ultimately included, with one randomized controlled trial and 26 observational studies. A total of 6568 patients were included. Meta-analysis showed that robotic surgery had less estimated blood loss ( P < 0.001), blood transfusion ( P = 0.04), intraoperative complications ( P = 0.001), and conversion to open surgery ( P = 0.001), and a shorter hospital stay ( P = 0.001), but had a longer operation time ( P = 0.04) in surgical staging of endometrial cancer compared with laparoscopy. There were no significant differences in postoperative complications, the total number of lymph nodes harvested, the number of pelvic lymph nodes harvested, and the number of para-aortic lymph nodes harvested between techniques. Robotic surgery had a longer operation time ( P = 0.008), less estimated blood loss ( P < 0.001), blood transfusion ( P < 0.001), and postoperative complications ( P < 0.001), and a shorter hospital stay ( P < 0.001) compared with laparotomy. There were no significant differences in other variables between techniques.; Conclusion: Robotic surgery is a safer surgical approach than laparoscopy and laparotomy in surgical staging of endometrial cancer, with less estimated blood loss, blood transfusion, and conversion, and the same number of lymph nodes harvested.; Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper. (Copyright © 2020 Jia Wang et al.)

Wang, J., et al. (2023). "The Role of Dehydroepiandrosterone in Improving in vitro Fertilization Outcome in Patients with DOR/POR: A Systematic Review and Meta-Analysis." Combinatorial Chemistry and High Throughput Screening 26(5): 916-927.
	Background and Objective: Although many trials have evaluated the use of dehydroepi-androsterone to improve outcomes in poor responders undergoing assisted reproductive technology treatment, evidence supporting this approach is controversial. We aimed to conduct a systematic review and meta-analysis of existing published data to further elucidate and supplement the use of Dehydroepiandrosterone (DHEA) to improve the effectiveness of vitro fertilization in patients with diminished ovarian reserve or adverse ovarian reactions. Method(s): PubMed, Embase, Cochrane Library, and the Web of Science databases were searched through December 2020. Oocyte yield, metaphase II oocytes, fertilized oocytes, top-quality embryos, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were analyzed as relative outcomes. Meta-analysis was performed and fitted to both fixed-effects models and random-effects models. Result(s): Eight prospective randomized controlled studies, five prospective case-control studies, and three retrospective cohort studies were conducted with a total of 1998 participants. Meta-analyses of these studies showed a significantly higher number of oocytes retrieved (WMD 1.09, 95% CI 0.38 to 1.80), metaphase II oocytes (WMD 0.78, 95% CI 0.16 to 1.40), fertilized oocytes (WMD 0.84, 95% CI 0.42 to 1.26), top-quality embryos (WMD 0.60, 95% CI 0.34 to 0.86), clinical pregnancy rate (RR 1.35, 95% CI 1.13 to 1.61), and ongoing pregnancy rate (RR 1.82, 95% CI 1.34 to 2.46), although there was no difference in live birth rate (RR 1.35, 95% CI 0.94 to 1.94) in the DHEA sup-plementation groups compared with that in the control groups. Conclusion(s): Oral DHEA supplementation appears to improve some IVF outcomes. On the basis of this limited evidence, we conclude that further studies are required to provide sufficient data.Copyright © 2023 Bentham Science Publishers.

Wang, J., et al. (2021). "Association of Myometrial Invasion With Lymphovascular Space Invasion, Lymph Node Metastasis, Recurrence, and Overall Survival in Endometrial Cancer: A Meta-Analysis of 79 Studies With 68,870 Patients." Frontiers in Oncology 11: 762329.
	Background: Myometrial invasion has been demonstrated to correlate to clinicopathological characteristics and prognosis in endometrial cancer. However, not all the studies have the consistent results and no meta-analysis has investigated the association of myometrial invasion with lymphovascular space invasion (LVSI), lymph node metastasis (LNM), recurrence, and overall survival (OS). Therefore, a meta-analysis was performed to evaluate the relationship between myometrial invasion and clinicopathological characteristics or overall survival in endometrial cancer.; Materials and Methods: A search of Pubmed, Embase, and Web of Science was carried out to collect relevant studies from their inception until June 30, 2021. The quality of each included study was evaluated using Newcastle-Ottawa scale (NOS) scale. Review Manager version 5.4 was employed to conduct the meta-analysis.; Results: A total of 79 articles with 68,870 endometrial cancer patients were eligible including 9 articles for LVSI, 29 articles for LNM, 8 for recurrence, and 37 for OS in this meta-analysis. Myometrial invasion was associated with LVSI (RR 3.07; 95% CI 2.17-4.35; p < 0.00001), lymph node metastasis (LNM) (RR 4.45; 95% CI 3.29-6.01; p < 0.00001), and recurrence (RR 2.06; 95% CI 1.58-2.69; p < 0.00001). Deep myometrial invasion was also significantly related with poor OS via meta-synthesis of HRs in both univariate survival (HR 3.36, 95% CI 2.35-4.79, p < 0.00001) and multivariate survival (HR 2.00, 95% CI 1.59-2.53, p < 0.00001). Funnel plot suggested that there was no significant publication bias in this study.; Conclusion: Deep myometrial invasion correlated to positive LVSI, positive LNM, cancer recurrence, and poor OS for endometrial cancer patients, indicating that myometrial invasion was a useful evaluation criterion to associate with clinical outcomes and prognosis of endometrial cancer since depth of myometrial invasion can be assessed before surgery. The large scale and comprehensive meta-analysis suggested that we should pay more attention to myometrial invasion in clinical practice, and its underlying mechanism also deserves further investigation.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Wang, Xu, Yang, Yu, Xu, Zou and Zhang.)

Wang, J.-F., et al. (2022). "Efficacy and Safety of Placebo During the Maintenance Therapy of Ovarian Cancer in Randomized Controlled Trials: A Systematic Review and Meta-analysis." Frontiers in Oncology 12: 796983.
	Introduction: This meta-analysis evaluated the efficacy and safety of placebo during the maintenance therapy of ovarian cancer (OC) patients in randomized controlled trials (RCTs).; Methods: A comprehensive literature review was performed for RCTs published up to and including August 2020 from four electronic databases. We analyzed the efficacy and safety in the control arms of the maintenance therapy in advanced OC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) were estimated in the placebo arms and the observation arms, respectively, using the Frequency Framework method. We also calculated the incidences of common adverse effects (AEs) in the placebo arms.; Results: In total, 41 articles with 20,099 (4,787 in the placebo arms, 3,420 in the observation arms, and 11,892 in the experiment arms) patients were included in this meta-analysis. Compared with observation, placebo did not improve or reduce PFS (HR, 1.02; 95% CI, 0.87-1.20; P = 0.81) and OS (HR, 1.02; 95% CI, 0.89-1.16; P = 0.76) of OC patients, while other treatments, except for radiotherapy, significantly improved PFS and OS (all P < 0.05). The incidences of AEs produced by placebo were 94.03% in all grades and 20.22% in grade ≥3. The incidences of AEs were 29.75% in fatigue, 26.38% in nausea, 24.34% in abdominal pain, 18.92% in constipation, 16.65% in diarrhea, 14.55% in vomiting, 13.89% in hypertension, and 13.14% in headache.; Conclusions: Placebo did not improve or reduce the PFS and OS benefits of OC patients in RCTs but increased the incidences of AEs.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Wang, Zhao, Bin, Zhang, Sun, Wang, Feng, Ji, He, Chen and Li.)

Wang, J. J., et al. (2022). "Needle knife in the treatment of primary dysmenorrhea: a systematic review and meta-analysis." TMR Integrative Medicine 6: e22022.
	Objective: The aim of this meta-analysis was to examine the effectiveness and safety of needle knives for primary dysmenorrhea. Method(s): We searched the electronic databases from their inception to May 25, 2022, comprising Cochrane Library, PubMed, Embase, SinoMed, CNKI, VIP and Wanfang databases. Randomized controlled trials (RCTs) investigating the effectiveness of needle knives for people with primary dysmenorrhea were eligible. The risk of bias and the quality of the included literature were evaluated. RevMan5.3 software was used for this study. Result(s): Five articles with 313 participants were involved in the review. The cure rate (2.82 (2.01, 3.95), I2 = 25%) and total effective rate (1.32 (1.10, 1.57), I2 = 65%) of the experimental group were higher than those of the control group. The dysmenorrhea symptom scores (-1.81 (-2.61, -1.01), I2 = 69%), TCM symptom scores (-4.19 (-6.06, -2.31), I2 = 0%) and adverse reactions (0.16 (0.05, 0.51), I2 = 0%) of the experimental group were lower than those of the control group. Conclusion(s): Needle knives may provide advantages in the treatment of primary dysmenorrhea. RCTs, including the larger sample, multi-center, high-quality and double-blind research, were required to further verify the efficacy of needle knives for primary dysmenorrhea.Copyright © 2022 By Author(s). Published by TMR Publishing Group Limited. This is an open access article under the CC-BY license. (https://creativecommons.org/licenses/by/4.0/)

Wang, K., et al. (2020). "Risk Factors for Postpartum Stress Urinary Incontinence: a Systematic Review and Meta-analysis." Reproductive sciences (Thousand Oaks, Calif.) 27(12): 2129-2145.
	Stress urinary incontinence (SUI) is a distressing symptom affecting females globally and is one of the most common complications of delivery. The etiology of female SUI is multifactorial, and the trauma caused by delivery is one of the most important risk factors for SUI. We performed a meta-analysis to determine the relationship between these various factors and postpartum SUI. We searched PubMed, Embase, Web of Science, and the Cochrane Library until January 2019 using appropriate keywords and extracted 46 eligible studies that included 73,010 participants. The study protocol was registered with PROSPERO (No. CRD42020150094). The pooled results indicated that 12 risk factors, including vaginal delivery (OR 2.08, 95% CI 1.72-2.52), advanced age at gestation (OR 1.06, 95% CI 1.04-1.08), advanced maternal BMI (OR 1.04, 95% CI 1.03-1.06), excess weight gain during pregnancy (OR 1.13, 95% CI 1.00-1.26), advanced current BMI (OR 1.32, 95% CI 1.02-1.70), diabetes (OR 1.91, 95% CI 1.53-2.38), episiotomy (OR 1.76, 95% CI 1.06-2.94), forceps delivery (OR 2.69, 95% CI 1.25-5.76), gestational UI (OR 5.04, 95% CI 2.07-12.28), gestational SUI (OR 4.28, 95% CI 2.61-7.01), prenatal UI (OR 8.54, 95% CI 3.52-20.70), and early postpartum UI (OR 3.52, 95% CI 1.61-7.69), were associated with postpartum SUI. The findings of this analysis could serve to generate risk prediction models and provide a basis for developing treatment strategies for patients with postpartum SUI.

Wang, L., et al. (2022). "Efficacy and Safety of Shuganjieyu Capsule Alone or in Combination with Other Antidepressants in the Treatment of Postpartum Depression: A Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2022: 5260235.
	Objective: To evaluate the efficacy and safety of Shuganjieyu capsule alone or in combination with other antidepressants in the treatment of postpartum depression.; Methods: Related control and randomized studies till August 1, 2021, were retrieved from the following databases: PubMed, Cochrane, CNKI, CMB, Wan-Fang, and VIP. Outcomes included HAMD reduction from baseline, response rate, and adverse events rate. Review Manager 5.3 was used in the present meta-analysis.; Results: 16 studies including 1409 participants were included in the present study. In comparison of single Shuganjieyu capsule versus regular antidepressant, 8, 6, and 4-week HAMD reduction of the Shuganjieyu group were significantly higher (8-week MD: 3.1 (1.54, 4.66), p < 0.0001; 6-week MD: 0.71 (0.10, 1.31), p =0.02; and 4-week MD: 0.82 (0.34, 1.30), p =0.0008), response rates were comparable for the two groups (OR: 1.51 (0.87, 2.63), p =0.014), and the adverse event rate of the Shuganjieyu group was significantly lower (OR: 0.22 (0.15, 0.32), p < 0.00001). In comparison of combination of Shuganjieyu capsule with regular antidepressant versus regular antidepressant alone, the 8, 6, 4, 2, and 1-week HAMD reduction and response rate of combination of Shuganjieyu with the regular antidepressant group were significantly larger (8-week MD: 3.2 (1.34, 5.06), p =0.0007; 6-week MD: 4.00 (2.72, 5.28), p < 0.00001; 4-week MD: 3.33 (1.94,4.73), p < 0.00001; 2-week MD: 2.69 (1.34, 4.03), p < 0.0001; 1-week MD: 2.27 (0.69, 3.86), p =0.005; and response rate OR: 4.69 (2.27, 9.68), p < 0.0001) and the adverse event rate was comparable for the two groups (OR: 1.26 (0.73, 2.17), p =0.41).; Conclusion: Compared with regular antidepressants, single Shuganjieyu capsule has similar efficacy and better safety profile; when Shuganjieyu capsule is combined with regular antidepressants, the efficacy is improved significantly without increasing adverse events. Therefore, Shuganjieyu capsule was effective and safe for postpartum, making it worth further investigation and popularization.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Lingning Wang et al.)

Wang, L., et al. (2019). "Is there a role for carbon therapy in the treatment of gynecological carcinomas? A systematic review." Future oncology (London, England) 15(26): 3081-3095.
	This Systematic Review summarizes the literatures of clinical trials on the efficacy and safety of carbon ion therapy for gynecological carcinomas. The protocol is detailed in the online PROSPERO database, registration no. CRD42019121424, and a final set of eight studies were included. In the treatment of cervical carcinomas, both carbon ion therapy alone and carbon ion therapy concurrent chemotherapy have presented good efficacy. Besides, the efficacy of inoperable endometrial carcinomas and gynecological melanoma are similar to that of surgical treatment. In terms of safety, gastrointestinal and genitourinary toxicities are low and could be controlled by limiting the volume and dose of intestinal tract and bladder. Carbon ion radiotherapy could be considered a safe, effective and feasible therapy for gynecological carcinomas.

Wang, L. and R. Yang (2023). "Comparison of therapeutic effects of Chinese herbal medicine and Western medicine on adenomyosis: A systematic review and meta-analysis." Asian journal of surgery.
	
Wang, L. and R. Yang (2024). "Comparing the therapeutic effects of Chinese herbal medicine with Western medicine on adenomyosis: A systematic review and meta-analysis." Asian journal of surgery 47(1): 578-580.
	
Wang, M., et al. (2021). "Meta-analysis of clinical trials of transcranial magnetic stimulation for chronic pelvic pain syndrome."
	
Wang, P. and L. Fang (2021). "Salpingo-oophorectomy versus cystectomy in patients with borderline ovarian tumors: a systemic review and meta-analysis on postoperative recurrence and fertility." World Journal of Surgical Oncology 19(1): 132.
	Background: To compare the postoperative recurrence and fertility in patients with borderline ovarian tumors (BOTs) who underwent different surgical procedures: salpingo-oophorectomy versus cystectomy.; Methods: Potentially relevant literature from inception to Nov. 06, 2020, were retrieved in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (Pubmed). We applied the keywords "fertility-sparing surgery," or "conservative surgery," or "cystectomy," or "salpingo-oophorectomy," or "oophorectomy," or "adnexectomy," or "borderline ovarian tumor" for literate searching. Systemic reviews and meta-analyses were performed on the postoperative recurrence rates and pregnancy rates between patients receiving the two different surgical methods. Begger's methods, Egger's methods, and funnel plot were used to evaluate the publication bias.; Result: Among the sixteen eligible studies, the risk of recurrence was evaluated in all studies, and eight studies assessed the postoperative pregnancy rates in the BOT patients. A total of 1839 cases with borderline ovarian tumors were included, in which 697 patients (37.9%) received unilateral salpingo-oophorectomy and 1142 patients (62.1%) underwent unilateral/bilateral cystectomy. Meta-analyses showed that BOT patients with unilateral/bilateral cystectomy had significantly higher recurrence risk (OR=2.02, 95% CI: 1.59-2.57) compared with those receiving unilateral salpingo-oophorectomy. Pooled analysis of four studies further confirmed the higher risk of recurrence in patients with cystectomy (HR=2.00, 95% CI: 1.11-3.58). In addition, no significant difference in postoperative pregnancy rate was found between patients with the two different surgical procedures (OR=0.92, 95% CI: 0.60-1.42).; Conclusion: Compared with the unilateral/bilateral cystectomy, the unilateral salpingo-oophorectomy significantly reduces the risk of postoperative recurrence in patients with BOT, and it does not reduce the pregnancy of patients after surgery.; Trial Registration: PROSPERO CRD42021238177.

Wang, P., et al. (2021). "Endometriosis-Related Pleural Effusion: A Case Report and a PRISMA-Compliant Systematic Review." Frontiers in Medicine 8: 631048.
	Background: Endometriosis-related pleural effusion (PE) is a relatively rare but treatable cause of bloody PE. The clinical characteristics and outcome of patients with endometriosis-related PE remain unknown. Objectives: We present a case of endometriosis-related PE diagnosed on pleural fluid cytology. A systematic review of all endometriosis-related PE cases in literature was conducted to elucidate the clinical characteristics, explore the diagnostic yield of pathological examinations, and to summarize the outcomes of therapeutic approaches in this disease. Methods: A case of endometriosis-related PE diagnosed in study hospital was reported. PubMed, Web of Science, and EMBASE were searched for publications pertaining to cases of endometriosis-related PE using predefined search terms. This case and those identified from PubMed, Web of Science, and EMBASE were analyzed. Results: A total of 67 patients were included. Catamential symptoms were presented in 30 (44.8%) patients. Dyspnea was presented in 50 patients (74.6%), followed by right chest/shoulder pain in 34 (50.7%) and cough in 18 (26.9%). 82.8% of the patients had concomitant pelvic endometriosis and 76.7% was infertile or nulliparous. The diagnostic yield of pleural fluid cytological examination, percutaneous pleural biopsy, and surgical biopsy was 9.0, 45.5, and 78.7%, respectively. The patients who received surgery-based therapy had a significantly longer time to relapse than those who received progestational agents or GnRH analogs alone ( P = 0.025) or hysterectomy and bilateral salpingoophorectomy (HBSO) ( P = 0.040). Conclusions: High clinical awareness of pleural endometriosis is essential in all female with hemorrhagic PE, especially in young females who have infertility and/or pelvic endometriosis. Plerual fluid cytology might be a simple minimally invasive and cost-effective modality in the diagnosis of endometriosis-related PE. Treatment is challenging due to high recurrence and the optimal management of endometriosis-related PE needs further evaluation. The combined approach by surgery and hormonal therapy may achieve the best relapse-free survival.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Wang, Meng, Li and Xu.)

Wang, R., et al. (2023). "Efficacy of atosiban for repeated embryo implantation failure: A systematic review and meta-analysis." Frontiers in Endocrinology 14: 1161707.
	Background: Repeated embryo implantation failure (RIF) posed a significant challenge in assisted reproduction. Evidence of its therapeutic effectiveness including atosiban used around embryo transfer to improve pregnancy outcomes in RIF patients undergoing in vitro fertilization-embryo transfer (IVF-ET) remained inconsistent. This study aimed to explore the efficacy of atosiban on pregnancy outcomes of patients with RIF who received IVF-ET.; Methods: The research was designed using the PICOS format. A systematic search of four English databases, PubMed, EMBASE, Web of Science, Cochrane Library, and one Chinse database, China National Knowledge Infrastructure (CNKI) was conducted. The time range was from inception to December 10, 2022. Then trials comparing the efficacy of atosiban and control group on pregnancy outcomes in RIF patients who receive IVF-ET were included. Subgroup analysis and sensitivity analysis were performed to reduce the influence of heterogeneity between included studies. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The main outcome measure was clinical pregnancy rate (CPR). For the analyses, StataMP 17.0 (Stata Corporation, USA) was used.; Results: Two prospective randomized controlled trials (RCTs), one prospective cohort study and four retrospective cohort studies were included. Our results showed that atosiban was associated with higher clinical pregnancy rate (RR=1.54, 95% CI: 1.365-1.735, P < 0.001, I 2 = 0.0%). The results of subgroup analysis based on study types (prospective randomized controlled clinical trial, retrospective cohort study and prospective cohort study) showed that in all types of studies, CPR of atosiban group was significantly higher than controlled group. The results of subgroup analysis based upon the diagnostic criteria of number of previous embryo transfer failures showed that the intervention of atosiban improved the CPR whether in participants with 2 previous ET failures or in participants with 3 previous ET failures. Nevertheless, the incidence of ectopic pregnancy, multiple pregnancy, and miscarriages were not significantly different between the case and control groups.; Conclusion: For women who are undergoing IVF-ET and have experienced repeated embryo implantation failure, atosiban may be an important factor in enhancing pregnancy outcomes. To confirm this conclusion, more thorough, prospective randomized controlled studies of sizable sample sizes with well design are required.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Wang, Huang, Tan and Xia.)

Wang, R., et al. (2019). "First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis." Human Reproduction Update 25(6): 717-732.
	Background: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine.; Objective and Rationale: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics.; Search Methods: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs.; Outcomes: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06).; Wider Implications: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS. (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Wang, R., et al. (2019). "Efficacy and Safety of Chinese Herbal Medicine on Ovarian Cancer After Reduction Surgery and Adjuvant Chemotherapy: A Systematic Review and Meta-Analysis." Frontiers in Oncology 9: 730.
	Background: Ovarian cancer (OvC) is a malignant tumor which invades ovarian epithelium and interstitium. Reduction surgery combined with adjuvant chemotherapy is standard treatment for OvC patients, but the adverse effects due to chemotherapy still remains a major problem. While Chinese herbal medicine (CHM) therapy has a unique therapeutic effect to reduce side effects of chemotherapy by boosting immune system, the evidence of CHM in the treatment of OvC patients are limited. Objective: We conducted a systematic review to evaluate the efficacy and safety of CHM in the treatment of OvC after reduction surgery and adjuvant chemotherapy. Method: Chinese National Knowledge Infrastructure (CNKI) and PubMed up to Dec 31st 2018 were searched to identify relevant studies. Only randomized controlled trials (RCTs) were included, and there was no limitation on language of the publication. Data were extracted from all included studies and meta-analysis was performed with Review Manager 5.3. Study quality was assessed and pooled risk ratios (RR) or mean difference (MD) with 95% CIs were used to evaluate the efficacy and safety of CHM. Results: A total of 18 RCTs involving 975 participants were included. There was no placebo, no treatment and CHM alone. Compared with Western Medicine (WM) alone, Chinese herbal Medicine combined with WM (CHM-WM) significantly improved TCM syndromes and symptoms, KPS scores, CD4 counts, CA125 levels, and 3-years survival rate ( P < 0.05). Incidences of gastrointestinal reactions, marrow depression, urinary system symptoms were significantly lower in CHM-WM group than in WM group ( P < 0.01). There was no significant difference in CD3 counts, CD8 counts, quality of life, liver function, and peripheral neuropathy between the two groups ( P > 0.05). Conclusion: The systematic review indicated that CHM combined with WM is effective and safe as a treatment for OvC patients after reduction surgery and adjuvant chemotherapy. However, more high-quality and large-scale RCTs are needed to confirm the efficacy and safety of CHM intervention.

Wang, R., et al. (2022). "Apical Support Procedures at the Time of Hysterectomy for Benign Indications: A Cost-Effectiveness Analysis." Obstetrics and Gynecology 139(5): 788-796.
	Objective: To assess the cost effectiveness of performing routine concurrent apical support procedures at the time of hysterectomy for benign indications.; Methods: We developed a Markov decision model from the health care sector perspective to compare concurrent apical support (ie, McCall culdoplasty) at the time of hysterectomy for benign indications compared with hysterectomy alone. We modeled Markov transitions between asymptomatic, prolapse without treatment, and treated prolapse states for 3 years. Our primary outcome was incremental cost-effectiveness ratio, defined as the difference between groups in mean cost (2019 U.S. dollars) divided by the difference in mean quality-adjusted life-years (QALYs). Model parameter estimates were taken from the published medical literature. Cost estimates were obtained from Medicare reimbursement rates and the literature. One-way, two-way, and probabilistic sensitivity analyses were performed.; Results: We assumed a base-case scenario of 13% posthysterectomy prolapse after hysterectomy alone and 2.1% after concurrent apical support, 5.8% and 0.9% undergoing subsequent surgical treatment for prolapse, respectively. Concurrent apical support at the time of hysterectomy had higher costs ($1,667 vs $1,423) but was more effective (2.34 vs 2.31 QALYs) than hysterectomy alone. Concurrent apical support was cost effective with an incremental cost-effectiveness ratio of $11,988/QALY, compared with general willingness-to-pay ranges of $50,000-150,000/QALY. In sensitivity analyses, concurrent apical support remained cost effective as long as the rate of posthysterectomy prolapse after concurrent apical support remained less than 8.7%. Monte Carlo simulation showed that concurrent apical support was cost effective in more than 60% of the simulated iterations.; Conclusion: Apical support at the time of hysterectomy for benign indications is cost effective compared with hysterectomy alone from the health care sector perspective at 3 years. Our results suggest that encouraging concurrent apical support procedures at time of hysterectomy is a cost-effective strategy in preventing posthysterectomy vaginal prolapse.; Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest. (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Wang, R., et al. (2023). "Cost effectiveness of concurrent midurethral sling at the time of prolapse repair: Results from a randomized controlled trial." Urogynecology 29(5): 461-468.
	Importance: The relative cost per improvement in quality of life can help guide decisions about adding a midurethral sling at the time of prolapse surgery. Objective(s): This study aimed to assess the cost-effectiveness of prophylactic midurethral slings placed at the time of prolapse surgery to reduce de novo urinary incontinence based on a randomized controlled trial. Study Design: Costs and effectiveness were collected as part of a planned secondary analysis from the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) trial, where 337 women without symptomatic stress urinary incontinence were randomly assigned to a midurethral sling or sham incisions during vaginal prolapse surgery. Within-trial cost-effectiveness analysis was performed from the societal perspective. Effectiveness was measured in quality-adjusted life-years (QALYs) and de novo urinary incontinence. We calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. Result(s): Within-trial societal costs were higher for the sling group than for the control group ($18,170 [95% confidence interval (CI), $16,420-$19,920] vs $15,700 [95% CI, $14,110-$17300], P = 0.041). The changes in QALY were 0.04 (95% CI, 0.02-0.06) versus 0.03 (95% CI, 0.02-0.05; P = 0.54). The incremental cost-effectiveness ratio for prophylactic sling was $309,620/QALY. This is above the generally accepted range of willingness-to-pay thresholds of $50,000 to $150,000/QALY. At 1 year, urinary incontinence was more common in the control group, and the cost to prevent 1 case was $91. The probability that prophylactic sling is cost-effective is 24%. Conclusion(s): Prophylactic sling placed during vaginal prolapse surgery reduced the rate of de novo urinary incontinence, but was not cost-effective.Copyright © 2023 Lippincott Williams and Wilkins. All rights reserved.

Wang, R., et al. (2019). "The effectiveness of tubal flushing with different contrast media on fertility outcomes: a systematic review and network meta-analysis." Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.
	OBJECTIVES: To compare the effectiveness and safety of tubal flushing with oil- or water-based contrast medium, alone or in combination, with each other or no tubal flushing in women with infertility; and to evaluate the effectiveness of tubal flushing on fertility outcomes over time. METHODS: We performed a systematic review and network meta-analysis. We searched electronic databases (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) and trial registries up to 25th September 2018. We included randomised controlled trials (RCTs) comparing the following interventions with each other or no intervention in women with infertility: tubal flushing with water-based contrast, oil-based contrast, or in combination. The outcomes included clinical pregnancy, live birth, ongoing pregnancy, miscarriage, ectopic pregnancy and adverse events. RESULTS: We included 14 RCTs reporting on 3,852 women with infertility. Network meta-analyses showed that tubal flushing with oil-based contrast resulted in more clinical pregnancies within 6 months and subsequent live births, compared to tubal flushing with water-based contrast (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.38-2.03, moderate certainty of evidence; OR 2.18, 95% CI 1.30-3.65, low certainty of evidence) and compared to no intervention (OR 2.28, 95% CI 1.50-3.47, moderate certainty of evidence; OR 2.22, 95% CI 1.44-3.42, low certainty of evidence). These results agreed with those in pairwise meta-analyses. There was insufficient evidence of a difference between tubal flushing with water-based contrast and no intervention (OR 1.36, 95% CI 0.91 to 2.04, low certainty of evidence). For fertility outcomes after 6 months, there was insufficient evidence of a difference in any comparisons (low to very low certainty of evidence). Compared to water-based contrast, oil-based contrast resulted in more asymptomatic intravasation (OR 5.06, 95% CI 2.29 to 11.18, moderate certainty of evidence). CONCLUSION: In women with infertility undergoing fertility work-up, tubal flushing with oil-based contrast probably increases clinical pregnancy rates within 6 months and may increase subsequent live birth rates, compared to tubal flushing with water-based contrast and compared to no intervention. Evidence on fertility outcomes beyond 6 months is insufficient. This article is protected by copyright. All rights reserved.

Wang, R., et al. (2019). "Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta-analysis." Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 54(2): 172-181.
	Objectives: To compare, in women with infertility, the effectiveness and safety of tubal flushing using oil-based contrast medium, water-based contrast medium or their combination, and no tubal flushing, and to evaluate the effectiveness of tubal flushing on fertility outcome over time.; Methods: We performed a systematic review and network meta-analysis, searching the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and trial registries, up to 25 September 2018. We included randomized controlled trials (RCTs) comparing the following interventions with each other or with no intervention in women with infertility: tubal flushing using water-based contrast medium, tubal flushing using oil-based contrast medium or additional tubal flushing with oil-based medium following diagnostic tubal flushing with water-based medium. The outcomes included clinical pregnancy, live birth, ongoing pregnancy, miscarriage, ectopic pregnancy and adverse events.; Results: Of the 283 studies identified through the search, 14 RCTs reporting on 3852 women with infertility were included. Network meta-analysis showed that tubal flushing using oil-based contrast medium was associated with higher odds of clinical pregnancy within 6 months after randomization and more subsequent live births compared with tubal flushing using water-based medium (odds ratio (OR), 1.67 (95% CI, 1.38-2.03), moderate certainty of evidence; and OR, 2.18 (95% CI, 1.30-3.65), low certainty of evidence, respectively) and compared with no intervention (OR, 2.28 (95% CI, 1.50-3.47), moderate certainty of evidence; and OR, 2.85 (95% CI, 1.41-5.74), low certainty of evidence, respectively). These results agreed with those of the pairwise meta-analysis. For clinical pregnancy within 6 months, there was insufficient evidence of a difference between tubal flushing with water-based contrast medium and no intervention (OR, 1.36 (95% CI, 0.91-2.04), low certainty of evidence). For fertility outcomes after 6 months, there was insufficient evidence of a difference in any comparison (low to very low certainty of evidence). Compared with tubal flushing using water-based contrast medium, the use of oil-based contrast medium was associated with higher odds of asymptomatic intravasation (OR, 5.06 (95% CI, 2.29-11.18), moderate certainty of evidence).; Conclusions: In women with infertility undergoing fertility workup, tubal flushing using oil-based contrast medium probably increases clinical pregnancy rates within 6 months after randomization and may increase subsequent live-birth rates, compared with tubal flushing using water-based contrast medium and compared with no intervention. Evidence on fertility outcomes beyond 6 months is inadequate to draw firm conclusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Wang, R., et al. (2020). "Tubal flushing for subfertility." The Cochrane Database of Systematic Reviews 10: CD003718.
	Background: Establishing the subgroup analysis of the fallopian tubes (tubes) is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and visualising patency on radiographs, ultrasonography or laparoscopy. Many women were noted to conceive in the first three to six months after tubal flushing, raising the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates. An important adverse event during tubal flushing is intravasation (backflow of contrast medium into the blood or lymphatic vessels),which could lead to embolism although it is asymptomatic in most cases.; Objectives: To evaluate the effectiveness and safety of tubal flushing with oil-soluble contrast media (OSCM) and water-soluble contrast media (WSCM) on subsequent fertility outcomes in women with subfertility.; Search Methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, MEDLINE, Embase, CENTRAL, PsycINFO, reference lists of identified articles and trial registries. The most recent search was conducted in April 2020.; Selection Criteria: Randomised controlled trials (RCTs) comparing tubal flushing with OSCM, WSCM with each other or with no treatment, in women with subfertility.; Data Collection and Analysis: Two review authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods.; Main Results: Fifteen trials involving 3864 women were included in this systematic review. Overall, the quality of evidence varied from very low to moderate: the main limitations were risk of bias, heterogeneity and imprecision. OSCM versus no treatment Four studies (506 women) were included in this comparison. Tubal flushing with OSCM may increase the odds of live birth (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.57 to 6.85, 3 RCTs, 204 women, I 2 = 0, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 11%, the chance following tubal flushing with OSCM would be between 16% and 46%. Tubal flushing with OSCM may increase in the odds of clinical pregnancy (OR 3.54, 95% CI 2.08 to 6.02, 4 RCTs, 506 women, I 2 = 18%, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 9%, the chance following tubal flushing with OSCM would be between 17% and 37%. No study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities. WSCM versus no treatment Only one study (334 women) was included in this comparison. We are uncertain whether tubal flushing with WSCM increase live birth compared to no treatment (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 21%, the chance following tubal flushing with WSCM would be between 15% and 33%. We are uncertain whether tubal flushing with WSCM increases clinical pregnancy compared to no treatment (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 27%, the chance following tubal flushing with WSCM would be between 29% and 40%. One case with pelvic infection was reported in the WSCM group and no case with infection in the no treatment group in a one study (334 women). Meta-analysis was not performed due to the rare events. No study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities. OSCM versus WSCM Six studies (2598 women) were included in this comparison. Three studies reported live birth, including two with higher live birth in the OSCM group (OR 1.64, 95%

Wang, S., et al. (2022). "Efficacy of Freeze-Dried Amnion Grafts on Cytokines in Uterine Exudates Following Hysteroscopic Adhesiolysis of Severe Intrauterine Adhesions." International Journal of General Medicine 15: 1703-1713.
	Background: Intrauterine adhesions (IUAs) are a benign uterine disorder that results in intrauterine adhesions and scarring. This study was conducted to assess the effects of freeze-dried amnion grafts on the concentrations of adhesion-related cytokines in uterine exudates following hysteroscopic adhesiolysis of IUAs. Material(s) and Method(s): This study was a prospective randomized controlled trial. Thirty patients who underwent hysteroscopic adhesiolysis for severe IUAs were enrolled. They were randomly divided into a study group (with freeze-dried amnion graft treatment after surgery, N = 15) and a control group (without a graft, N = 15). After complete separation of adhesions, a Foley balloon containing a freeze-dried amnion graft was inserted into the uterine cavity in the study group, while a Foley balloon with no graft was placed in the control group. Enzyme-linked immunosorbent assays were performed to test adhesion-related cytokine concentrations in uterine exudates, including IL-1beta, TNF-alpha, and VEGF, at different time intervals after surgery. Second-look hysteroscopy was conducted three months after the surgery. On the basis of the American Fertility Society (AFS) scoring system, the level of adhesions was evaluated during hysteroscopy. Result(s): The postoperative volume of the uterine exudates in the study group was significantly lower than that of the control group (P < 0.05). The adhesion-related cytokine concentrations of TNF-alpha, VEGF, and IL-1beta significantly increased after surgery in both groups. Their concentrations were significantly lower in the study group than in the control group (P < 0.05). Moreover, IL-1beta exhibited a long-lasting effect in the study group. AFS scores and readhesion rates were significantly lower in the study group than in the control group after hysteroscopic adhesiolysis of severe IUAs. Conclusion(s): The application of freeze-dried amnion grafts is beneficial to the postoperative recovery of patients with severe IUAs and may reduce the readhesion rate after hysteroscopic adhesiolysis by lowering adhesion-related cytokines, including TNF-alpha, VEGF, and IL-1beta.Copyright © 2022 Wang et al.

Wang, T., et al. (2021). "Effects of Repetitive Transcranial Magnetic Stimulation on Depression Symptoms and Cognition in Postpartum Depression: A Meta-analysis."
	
Wang, T. H., et al. (2021). "Effectiveness of nurses and midwives-led psychological interventions on reducing depression symptoms in the perinatal period: A systematic review and meta-analysis." Nursing Open.
	AIM: To evaluate the effectiveness of nurses and midwives-led psychological interventions on the perinatal depressive symptoms. DESIGN: A systematic review and meta-analysis based on the PRISMA guidelines. METHODS: Six databases were searched, including PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science and CINAHL. The search date range was before 30 September 2019. We used the Cochrane risk of bias tool to evaluate the quality of the included studies and Review Manager software 5.3 to conduct a meta-analysis. The data were pooled using a random-effect model. RESULTS: Studies (N = 827) were retrieved with 12 studies included. Psychological interventions provided by nurses and midwives have a significant effect on reducing perinatal depressive symptoms (RR: 0.72, 95% CI [0.64-0.82]). Among the approaches of psychological intervention, supportive counselling was the most effective (RR: 0.58, 95% CI [0.42-0.80]). The best intensity of intervention was six to eight sessions (RR: 0.66, 95% CI [0.55-0.79]).

Wang, T. H., et al. (2021). "Evaluation of psychological training for nurses and midwives to optimise care for women with perinatal depression: a systematic review and meta-analysis." Midwifery 104: 103160.
	Objective Perinatal depression is linked to poor maternal health and infant development outcomes. The World Health Organization recommends expanding the mental health education and training of primary care providers to improve the quality of perinatal depression care. The present study evaluated the effect of various psychological training methods on nurses' and midwives' competence in administering care to and alleviating symptoms in patients with perinatal depression. Methods A comprehensive search of the PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science, and CINAHL databases was performed. The data were independently extracted by two reviewers, and the critical appraisal tools of the Joanna Briggs Institute were used for quality assessment. Random-effects meta-analysis was conducted using Review Manager 5.4 software. Findings A total of 13 articles including 246 nurses and midwives and 4,381 perinatal women were reviewed. Care administered through both face-to-face (relative risk [RR] 0.70, 95% confidence interval [CI] 0.61-0.74) and digital training (RR 0.44, 95% CI 0.26-0.74) significantly mitigated symptoms of perinatal depression. Significant benefits were observed after 3- to 5-day and 8-day training, for which the RR were 0.75 (95% CI 0.59-0.97) and 0.72 (95% CI 0.66-0.85), respectively. Studies with high intervention fidelity more effectively reduced the risk of depressive symptoms in perinatal women than those with low intervention fidelity. Key conclusions and implications for practice Compared with face-to-face, digital training methods were more effective in reducing the risk of depressive symptoms. High intervention fidelity and 3- to 5-day and 8-day training resulted in better outcomes. The present findings can serve as a reference for the design of psychological training programs for nurses and midwives to equip them with effective strategies for administering care to patients with perinatal depression.

Wang, T. S., et al. (2020). "Effectiveness of electroacupuncture (EA) for the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI): A protocol of systematic review of randomized controlled trials." Medicine (United States) 99(30): E21077.
	Background:The objective of this study is to examine the effectiveness and safety of electroacupuncture (EA) in the treatment of urinary incontinence (UI) in patients with spinal cord injury (SCI). Method(s):All potential studies will be retrieved from the electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, Web of Science, CBM, and China National Knowledge Infrastructure from origin of each database up to January 31, 2020. Additionally, we will check other resources, such as Google scholar, dissertations, conference proceedings, and reference lists of included studies. No language and publication date limitations will be considered in the literature resources search. All randomized controlled trials using EA for the treatment of UI in patients with SCI will be included. Two independent investigators will perform study selection, data extraction and study quality assessment. If any conflicts occur, we will invite a third investigator to solve them. Cochrane risk of bias will be used for study quality assessment, and RevMan 5.3 software will be employed for statistical analysis. Result(s):This study will summarize the most recent evidence to assess the effectiveness and safety of EA for the treatment of UI in patients with SCI. Conclusion(s):The results of this study will provide helpful evidence to determine whether EA is effective and safety for the treatment of UI in patients with SCI or not.PROSPERO registration number:PROSPERO CRD42020165562.Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

Wang, W., et al. (2019). "Effect of preconceptional DHEA treatment on in vitro fertilization outcome in poor ovarian respond women: study protocol for a randomized controlled trial." Trials 20(1): 50.
	Background: Women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with poor ovarian respond (POR) always have very low clinical pregnancy rates. In previous data, dehydroepiandrosterone (DHEA) was suggested as a promising treatment and maybe has a good pregnancy outcome. But there is no sufficient evidence from randomized clinical trials evaluating the effect of DHEA preconceptional treatment on live birth in POR.; Methods: This trial is a multicenter active-placebo double-blind clinical trial (1:1 treatment ratio of active versus placebo). The infertile POR patients undergoing IVF or ICSI will be enrolled and randomly assigned to two parallel groups. Participants in these two groups will be given 4-12 weeks' treatment of DHEA or placebo, respectively. The primary outcome is live birth rate.; Discussion: The results of this study will provide evidence for the effect of preconceptional DHEA treatment on IVF outcome in POR.; Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-15006909 . Registered on November 9, 2015.

Wang, W. and H. Zhu (2022). "The function of letrozole in endometrial receptivity (ER) of patients with polycystic ovary syndrome (PCOS): a systematic review and meta-analysis of randomized controlled trials."
	
Wang, W. M., et al. (2020). "Effect of pelvic floor function intervention on pelvic floor anal function in rectal cancer patients with anus preservation." Chin. J. Cancer Prev. Treat. 27(5): 413-418.
	
Wang, X., et al. (2023). "The effect of recryopreservation on embryo viability and outcomes of in vitro fertilization: a systematic review and meta-analysis." Fertility and Sterility 120(2): 321-332.
	Objective: To investigate the impact of recryopreservation on embryo viability and the outcomes of in vitro fertilization (IVF) by comparison with single cryopreservation. There is a lack of consensus and reliable evidence regarding the impact of recryopreservation techniques on human embryos, particularly with respect to embryo viability and IVF outcomes.; Design: Systematic review and meta-analysis.; Setting: Not applicable.; Intervention(s): Various databases such as PubMed, Embase, Cochrane Library, and Scopus were searched until October 10, 2022. All comparative studies comparing embryonic and IVF outcomes between repeated and single cryopreservation of embryos were included. The random-effect and fixed-effect meta-analysis models were used to pool the odds ratio (OR) and corresponding 95% confidence intervals (CIs). A subgroup analysis was performed based on different methods of cryopreservation and different times of embryo cryopreservation or transfer.; Main Outcome Measure(s): Outcomes referring to embryo surviva l, IVF outcomes (including clinical pregnancy rate, embryo implantation rate, miscarriage rate, and live birth rate), and neonatal outcomes (including low birth weight rate and preterm birth rate) were evaluated.; Result(s): Fourteen studies were eligible for the present meta-analysis, involving 4,525 embryo transfer cycles in total (3,270 cycles with single cryopreservation [control group] and 1,255 with recryopreservation [experimental group]). Decreased embryo survival (OR, 0.51; 95% CI, 0.27-0.96) and clinical pregnancy rates (OR, 0.47; 95% CI, 0.23-0.96) were found in embryos that were recryopreserved by slow freezing. The live birth rate of revitrified embryos was also notably affected (OR, 0.60; 95% CI, 0.38-0.94). Overall, recryopreservation resulted in a decreased live birth rate (OR, 0.67; 95% CI, 0.50-0.90) and an increased miscarriage rate (OR, 1.52; 95% CI, 1.16-1.98) compared with single cryopreservation. No significant difference was found in neonatal outcomes. When embryos were cryopreserved and transferred at the blastocyst stage, both the embryo implantation rate (OR, 0.59; 95% CI, 0.39-0.89) and live birth rate (OR, 0.60; 95% CI, 0.37-0.96) were significantly different between the 2 groups.; Conclusion(s): The present meta-analysis suggested that recryopreservation, compared with single cryopreservation, can lead to impaired embryo viability and a lower rate of IVF success, with no affected neonatal outcomes. Clinicians and embryologists should retain a cautious attitude toward recryopreservation strategies.; Registration Number: CRD42022359456. (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Wang, X., et al. (2021). "Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics 38(9): 2237-2249.
	Objective: Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes.; Methods: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale.; Results: Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I 2 = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I 2 = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I 2 = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate.; Conclusion: Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS. (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wang, X., et al. (2020). "The effectiveness and safety of acupoint catgut embedding for the treatment of primary dysmenorrhea: A protocol for systematic review and meta-analysis." Medicine 99(47): e23222.
	Background: Primary dysmenorrhea (PD), also regarded as functional dysmenorrhea, refers to dysmenorrhea without obvious organic lesions in the reproductive system. It accounts for more than 90% of dysmenorrhea and seriously affects womens life and work. Previous studies have proved that acupoint catgut embedding therapy is effective and safe for PD patients. It could relieve the pain rapidly and work for a long time in multiple mechanisms. This protocol aims to evaluate the effectiveness and safety of acupoint catgut embedding therapy on PD systematically. With the latest published evidence, a systematic review and meta-analysis of catgut embedding for patients with PD would be carried out in this study.; Methods: All randomized controlled trials (RCTs) related to acupoint catgut embedding therapy on PD will be searched in the following electronic databases: PubMed, Cochrane Library, EMBASE, Wed of Science, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP Database, Wanfang Database, and Chinese Biomedical Literatures Database (CBM), from inception to September 2020. The primary outcomes contain visual analog scale (VAS), dysmenorrhea symptom score, and clinical effectiveness rate, while the secondary outcomes consist of adverse events and the recurrence rate. Two reviewers will independently perform data selection, data synthesis, and quality assessment. Assessment of risk of bias and data synthesis would be performed with Review Manager 5.3 software.; Result: This systematic review will summarize the current and high-quality evidence of acupoint catgut embedding therapy on PD.; Conclusion: This systematic review aims to offer the latest persuasive evidence for clinical practitioners that using acupoint catgut embedding therapy on PD is effective and safe.; Prospero Registration Number: CRD42020156362.

Wang, X., et al. (2022). "The clinical characteristics and treatment of ovarian malignant mesoderm mixed tumor: a systematic review." Journal of Ovarian Research 15(1): 104.
	Background: Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical features, pathology and molecular biology characteristic of published cases.; Methods: The English and Chinese reported cases of OMMMT were selected from PubMed, Clinical Trials.gov and CNKI database from 2000 to December 15th, 2021 following the PRISMA guidelines.; Results: A total of 63 literatures including 199 OMMMT cases were included. The average age of patients at diagnosis was 56.46 years, the highest incidence age was 60-65 years, and 82% of them were menopausal women. Most patients were diagnosed in FIGO III stage (59.64%). The most common symptom of OMMMT was abdominal pain (60.5%). 61.6% of patients were accompanied by ascites, while ascites was not associated with metastatic tumor and local recurrence. The CA125 of 88.68% patients increased. The most common reported carcinomatous component and sarcomatous component were serous adenocarcinoma (44.96%) and chondrosarcoma (24.81%), respectively. Initial treatment included surgery (94.97%) and taxanes-based (55.10%) or platinum-based (85.71%) chemotherapy regimens. The median survival time of patients was 20 months. Heterologous sarcoma component did not shorten life expectancy. The optimal ovarian tumor cell debulking surgery (OOTCDS), radiotherapy and chemotherapy could significantly prolong the median survival time of patients. Furthermore, platinum drugs could significantly prolong the survival time after comparing various chemotherapy schemes. Besides, the combination of platinum and taxanes was therapeutically superior to the combination of platinum and biological alkylating agents.; Conclusion: The OOTCDS and platinum-based chemotherapy regimen can improve the prognosis of OMMMT. Targeted therapy might become a new research direction in the future. Since the elderly patients are the majority, the toxicity of new drugs on the elderly patients is more noteworthy. (© 2022. The Author(s).)

Wang, X. and Y. Wang (2023). "The Effectiveness of Mindfulness-Based Intervention on Emotional States of Women Undergoing Fertility Treatment: A Meta-Analysis." Journal of sex & marital therapy 49(3): 249-258.
	For many infertile women, their inability to fulfill their aspirations and match society's expectations of motherhood may lead to mental illness. They frequently select in vitro fertilization (IVF) to achieve their wish to have children. In vitro fertilization is actually a multi-dimensional stressor. There are numerous psychological methods to assist patients decrease stress, among which mindfulness-based intervention is a prominent one. However, the effectiveness of mindfulness intervention in this group remains debatable. Therefore, our research seeks to evaluate the efficacy of mindfulness intervention in improving the emotional state of women undergoing in vitro fertilization by systematic review and meta-analysis, so as to provide a novel treatment plan for psychological therapy of this group. A meta-analysis was undertaken by scanning English databases PubMed, Embase, Cochrane library, Web of science, etc. Among them, the retrieval period is from the foundation of the database until July 5, 2022. Two investigators examined the literature according to the inclusion and exclusion criteria, and conducted meta-analysis using stata15.0 software. Six studies involving 964 infertile women were included. According to the meta-analysis, mindfulness was more effective than the control group in reducing anxiety, depression, and correlations in infertile women [standard mean difference, SMD = -0.31, 95% confidence interval (CI): -0.56 to -0.06], [SMD = -0.94, 95% CI: -1.84 to -0.03], [ r = 0.38, 95% CI: 0.25-0.52]. In terms of mindfulness and self-compassion, there was no significant difference between the intervention and control groups [SMD = 0.73, 95% CI: -0.38 to -1.85], [SMD = 0.09, 95% CI: -0.19 to -0.37]. As an intervention strategy for infertile women with anxiety and despair, mindfulness intervention might be a treatment priority.

Wang, X., et al. (2020). "Moxibustion for the treatment of primary dysmenorrhea: Protocol for an overview of systematic reviews." Medicine 99(4): e18908.
	Background: Primary dysmenorrhea (PD) is a common gynecological disease, it refers to spasmodic pain in the lower abdomen before, after or during menstruation, accompanied by general discomfort, In severe cases, fainting may occur due to severe pain, reducing the quality of patients' life and imposing a heavy burden on social medical security system. There are many ways to treat primary dysmenorrhea, including western medicine and traditional Chinese medicine. Moxibustion is one of the traditional Chinese medicine treatments for primary dysmenorrhea, especially popular in China. Therefore, our overview aims at evaluating the methodological bias and the reliability of the conclusions of systematic reviews (SRs) about moxibustion for primary dysmenorrhoea, and help clinical decision makers translate this research into clinical policy and practice.; Methods: We will search electronic databases including PubMed, Embase, Cochrane Library, Chinese Biomedical Literatures Database (CBM), China National Knowledge Infrastructure (CNKI), WangFang Database (WF), Chinese Scientific Journal Database (VIP) from inception to February 2017. We will consider systematic reviews and meta-analysis of randomized controlled trials evaluating the effect of moxibustion for PD. Two reviewers will identify relevant studies, extract data information, and then assess the methodological quality by Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report checklist to assess the quality of reports included in the study. We will use the evaluations of the Classification of Recommendations, Evaluation, Development and Evaluation (GRADE) of the authors of the included systematic reviews. The screening of systematic reviews, eligibility evaluation, data extraction, methodological quality, and quality of evidence will be conducted by independent reviewers in pairs. The outcomes of interest include: total effective rate, visual analog scale scores (VAS), Cox Menstrual Symptom Scale (CMSS), Dysmenorrhea symptom score and adverse events outcomes prioritized in the individual reviews. We will extract data onto a predefined form designed to summarize the key characteristics of each review. The evidence will be a narrative synthesis organized around the type and content of the intervention and the results reported.; Results: The results of this study will be published in a peer-reviewed journal.; Conclusions: We expect to compile evidence from multiple systematic reviews of symptomatic improvement in patients with primary dysmenorrhea in an accessible and useful document.; Registration Number Prospero: CRD42019141130.

Wang, X., et al. (2023). "Acupuncture at Sanyinjiao(SP6) for patients with primary dysmenorrhea: Protocol for a systematic review and meta-analysis." MedRxiv.
	Background: Primary dysmenorrhea (PD) is a gynecological disease that seriously affects women 's physical and mental health and quality of life. Sanyinjiao (SP6) is the most used acupoint for acupuncture treatment of PD, and acupuncture SP6 is more commonly used in the clinical treatment of PD, but evidence of effectiveness and safety is lacking. The purpose of this systematic review plan is to develop a study protocol that can evaluate the efficacy and safety of acupuncture SP6 in the treatment of PD. Method(s): The upper limit of retrieval time will be set to September 2023. Foreign and Chinese databases will be searched respectively: Cochrane Library, PubMed, EMBASE, Ovid, Korea Med, J-Global, J-Stage databases, and CNKI, CBM, SinoMed, VIP, Wanfang. Randomized controlled trials meeting the inclusion criteria will be screened by two independent reviewers, and data extraction and risk of bias assessment will be carried out. The primary outcome is dysmenorrhea symptoms, and the secondary outcomes include recent clinical cure rate, concomitant symptoms, serum prostaglandins, uterine artery blood flow resistance under ultrasound monitoring, and adverse reactions. Use RevMan V.5.3 software to perform the following operations: data synthesis, subgroup analysis, heterogeneity analysis, and sensitivity analysis. The evidence quality of clinical studies included in this study will be evaluated by the software of " Grading of Recommendations Assessment, Development, and Evaluation ". Result(s): This study will provide comprehensive clinical evidence for treating PD with acupuncture SP6. Conclusion(s): This systematic review will confirm whether acupuncture SP6 is safe and effective in treating PD clinically.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Wang, X., et al. (2023). "Chinese herbal medicine for primary dysmenorrhea: A systematic review and network meta-analysis of 54 randomized controlled trials." European journal of integrative medicine 63: 102293.
	Introduction: Primary dysmenorrhea (PD) is a common gynecological complaint among adolescents and young women. Chinese herbal medicines (CHMs) have been widely used for PD treatment in China. However, the relative advantages of different CHM regimens remain uncertain. This systematic review aimed to compare the efficacy and safety of different CHMs for the treatment of PD using network meta-analysis. Method(s): We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature Database (CBM) from their inception to December 17, 2022. Randomized controlled trials (RCTs) comparing CHM or Chinese patent drugs with Prostaglandin Synthetase Inhibitors (PGSIs) were included. Risk of bias was assessed using the Cochrane risk of bias tool. A frequentist framework network meta-analysis was performed using R (4.2.2). Result(s): A total of 54 RCTs with 5,345 PD patients were included. Compared with PGSIs, Danggui Sini decoction (mean difference [MD] = -5.92, 95% confidence interval [CI] -8.64 to -3.20) and Xiangfu Siwu Decoction (MD = -4.63, 95%CI -8.37 to -0.89) reduced pain significantly.; Danggui Sini decoction (risk ratio[RR] = 1.31, 95%CI 1.12 to 1.53), Danggui shaoyao san (RR = 1.23, 95%CI 1.05 to 1.44), Siwu decoction (RR = 1.32, 95%CI 1.17 to 1.47), Taohong Siwu Decoction (RR = 1.35, 95%CI 1.14 to 1.61), and Wenjing decoction (RR = 1.33, 95%CI 1.19 to 1.52) showed significantly higher overall response rates, and Wenjing decoction could significantly reduce TCM syndrome scores (MD = -4.14, 95%CI -6.84 to -1.44), compared with PGSIs. No serious adverse events were observed. Siwu decoction and Wenjing decoction ranked as the top treatment options in terms of all outcomes of interest (P-score ranking). Conclusion(s): CHMs were associated with improved overall response rate, pain reduction, and alleviation of symptoms compared to conventional treatments for patients with PD, and no serious adverse events were observed. However, the confidence in the conclusions is limited because of the lack of high-quality trials.Copyright © 2023 Elsevier GmbH

Wang, X., et al. (2023). "Effects of stem cell factor in follicular fluid and granulosa cells on oocyte maturity and clinical pregnancy." Medicine 102(52): e36749.
	Stem cell factor (SCF) is implicated in cell growth, proliferation, differentiation, migration, and apoptosis. SCF in follicular fluid (FF) and granulosa cells (GCs) plays a key role in oocyte maturation and clinical pregnancy; however, the exact mechanism is unclear. We aimed to investigate SCF potential in predicting oocyte maturity and clinical pregnancy. We collected 60 FF and 60 GCs samples from different patients with infertility. Real-time polymerase chain reaction and cellular immunofluorescence analyses were used to quantitatively and qualitatively determine SCF concentration in GCs; enzyme-linked immunosorbent assay was used to determine SCF concentration in FF. GC and FF SCF concentrations were positively correlated with metaphase (M)II oocyte proportion and clinical pregnancy (R = 0.280, 0.735 vs R = 0.257, 0.354). SCF concentrations in GCs were significantly higher in the clinical pregnancy group than in the nonclinical pregnancy group. Immunofluorescence analysis showed that SCF expression was higher in the clinical pregnancy and high-MII -oocyte proportion groups. Receiver operating characteristic curve analysis showed that combined SCF and serum anti-Müllerian hormone levels could predict oocyte maturity and clinical pregnancy better than either of these factors alone. SCF concentration in GCs and FF can serve as a predictor of oocyte maturity and clinical pregnancy.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Wang, Y., et al. (2020). "Effect of combined intravenous-inhalation anesthesia on postoperative cognitive dysfunction after laparoscopic radical resection of cervical cancer: A protocol for systematic review and meta-analysis." Medicine 99(45): e23124.
	Objective: To evaluate the effect of combined intravenous-inhalation anesthesia (CIVIA) on postoperative cognitive dysfunction (POCD) after laparoscopic radical resection of cervical cancer.; Methods: By using a predefined standardized study protocol, we conducted a systematic review of randomized controlled trials (RCTs) with meta-analysis, searching the following data bases: PubMed, Embase, Web of Science, and Cochrane Library.; Results: This systematic review evaluated the effect of CIVIA on POCD after laparoscopic radical resection of cervical cancer.; Conclusion: This systematic review provided up-to-date evidence to evaluate the effect of CIVIA on POCD after laparoscopic radical resection of cervical cancer.; Osf Registration Number: DOI 10.17605/OSF.IO/82FNA.

Wang, Y., et al. (2023). "Oncological and reproductive outcomes of conization combined with pelvic node evaluation in patients with early-stage cervical cancer: a systematic review and meta-analysis." Frontiers in Oncology 13: 1251453.
	Objective: This study aims to preliminarily assess the oncological and reproductive outcomes of fertility preservation treatment using conization combined with pelvic node evaluation in young patients with early-stage cervical cancer (ECC) through meta-analysis.; Methods: In this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to 0 7/02/2023.; Results: There were 17 relevant studies with a total of 620 patients included, of which 444 patients received conization combined with pelvic node evaluation. The combined pregnancy rate was 45.4% (95% CI: 0.34-0.57), the combined live birth rate was 33.9% (95% CI: 0.26-0.42), the combined miscarriage rate was 4.8% (95% CI: 0.02-0.092), the combined preterm delivery rate was 5.1% (95% CI: 0.02-0.092), and the combined recurrence rate was 1.9% (95% CI: 0.006-0.035), which did not significantly differ from that of patients who received radical surgery (OR: 0.689, 95% CI: 0.506-0.938).; Conclusion: Cervical conization combined with pelvic lymph node evaluation for fertility preservation in young ECC patients can achieve oncological outcomes similar to radical surgery while improving pregnancy success rates and preserving postoperative fertility. In summary, fertility preservation treatment using cervical conization combined with pelvic lymph node evaluation may be considered as a viable option for young ECC patients with strong fertility preservation desire, resulting in better pregnancy and live birth outcomes.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier PROSPERO (CRD42023423432).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Wang, Chen, Wang, Qin, Zhang, Zheng and Han.)

Wang, Y., et al. (2020). "Non-pharmacological interventions for postpartum depression: A protocol for systematic review and network meta-analysis." Medicine 99(31): e21496.
	Background: Postpartum depression (PPD) is one of the most common mental disorders in women following childbirth with heightened prevalence across the globe. Both pharmacotherapy and non-pharmacological interventions are effective for PPD. However, due to the concerns about the side effect on the mother and child of pharmacological treatments, most of women with PPD choose non-pharmacological therapies as their first line option. Prescription of these non-drug approaches should be guided by high quality evidence. Therefore, this network meta-analysis aims to compare, rank and interpret existed non-pharmacological evidence for the effective treatment of women with PPD.; Methods: Electronic bibliographic databases including EMBASE, PubMed, Scopus, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI),VIP Database, Wanfang Database and Chinese Biomedical Literature Database will be searched for relevant randomized controlled trials (RCTs) of non-pharmacological interventions for PPD. Heterogeneity and inconsistencies will be analyzed by I statistic and Z test, respectively. We will assess the quality of evidence by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and evaluate the risk of bias according to Cochrane risk of bias tool. R software 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria) will be used to conduct a network meta-analysis.; Results: Formal ethical approval is not required, because the present study is a meta-analysis based on existed studies. The findings of this research will be reported in a recognized journal.; Conclusion: The review results will ascertain the hierarchy of effectiveness of different non-pharmacological approaches for PPD, and systematically provide suggests for physicians and patients.; Trial Registration Number: PROSPERO CRD42020166801.

Wang, Y., et al. (2020). "A network meta-analysis protocol of conservative interventions for urinary incontinence in postpartum women." Medicine (United States) 99(33): E21772.
	Background:Postpartum urinary incontinence (PPUI) is a common urological condition in women after childbirth. Due to the side effects of surgical and pharmacological therapies, the patients and physicians alike express a strong preference for conservative approaches on PPUI, such as pelvic floor muscle training, biofeedback, electrical stimulation, bladder training, vaginal cones and acupuncture. Application of these conservative approaches should be guided by high quality evidence, yet their comparative effectiveness has not been well documented. Therefore, the network meta-analysis aims to compare, rank and summarize all available studies to determine which conservative intervention is more effective for PPUI. Method(s):In this present study, qualified English and Chinese studies will be searched in PubMed, Scopus, EMBASE, The Cochrane Library, Web of Science, VIP Database, Wanfang Database, Chinese Biomedical Literature Database and China National Knowledge Infrastructure. All eligible randomized controlled trails (RCTs) of conservative interventions for PPUI will be included. R software 3.61 (R Foundation for Statistical Computing, Vienna, Austria) will be applied to synthesize data and conduct network meta-analysis. I2 statistic and Z test will be used to assess heterogeneity and inconsistency, respectively. Result(s):Ethical approval is not required for this existed literature based meta-analysis. The findings of this research will be disseminated through a recognized journal. Conclusion(s):The findings of this study will provide ranking evidence for clinicians and patients to choose a more appropriate conservative therapy on PPUI.Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

Wang, Y., et al. (2022). "Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta-analysis." The Journal of Obstetrics and Gynaecology Research 48(9): 2270-2284.
	Aim: This meta-analysis was conducted to evaluate the impact of BRCA mutations on survival outcomes of ovarian cancer patients and assess whether the BRCA status was an independent predictor of complete cytoreduction.; Methods: We searched the PubMed, Cochrane, EMBASE, Scopus, Web of Science, and Google Scholar databases for studies that evaluated the associations among BRCA mutations, ovarian cancer survival and surgical cytoreduction before August 2021 based on specific inclusion and exclusion criteria.; Results: We identified 61 articles that compared the clinical features, survival outcomes, and optimal surgical cytoreduction rates between BRCA-positive patients and BRCA-negative patients. The results showed that BRCA mutation carriers were diagnosed with ovarian cancer at a younger age than the age at which nonmutation carriers were diagnosed. In addition, BRCA mutation carriers were more likely to be in the International Federation of Gynecology and Obstetrics (FIGO) stage III-IV, and the pathological grade was commonly grade 3. The pathological type of BRCA mutation carriers was more likely to be high-grade serous carcinoma. Patients with BRCA mutations had higher response rates to platinum-based chemotherapy than the noncarriers. However, patients in both groups had equivalent rates of surgical cytoreduction, and BRCA-positive patients had longer overall survival (OS) time (HR = 0.65; 95% confidence interval [CI]: 0.59, 0.73; p < 0.001) and longer progression-free survival (PFS) (HR = 0.72; 95% CI: 0.63, 0.82; p < 0.001).; Conclusion: BRCA mutations appear to be associated with improved OS and PFS in patients with ovarian cancer. However, we did not find any difference in the surgical resection rate between participants in the two groups. (© 2022 Japan Society of Obstetrics and Gynecology.)

Wang, Y., et al. (2019). "No Effect of Metformin on Ovarian Cancer Survival: A Systematic Review and Meta-Analysis of Cohort Studies." Current Pharmaceutical Design 25(23): 2595-2601.
	Background: A number of observational studies examined the association between metformin therapy and ovarian cancer survival outcomes, but the results are inconsistent.; Objective: The study aimed to investigate the effect of metformin on survival for ovarian cancer patients.; Method: PubMed, Embase and Web of Science databases were searched for relevant studies from the inception to June 11, 2019. The strength of the relationship was assessed using summary of hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Statistical analyses were carried out using the random-effects model.; Results: Totally, 6 retrospective cohort studies involving 2,638 ovarian cancer patients were included. Metformin was not associated with improved overall survival (HR=0.78, 95% CI 0.54-1.12, P=0.175, I2= 61.6%) and disease- free survival (HR=0.49, 95% CI 0.20-1.17, P=0.106, I2=82.1%) in ovarian cancer patients compared to nonmetformin users.; Conclusion: The current study provides preliminary evidence that metformin may not be associated with a survival benefit for ovarian cancer patients. More studies with rigorous designs are needed. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Wang, Y., et al. (2019). "The association between metformin and ovarian cancer survival: a systematic review and meta-analysis of cohort studies." Current Pharmaceutical Design 25(23): 2595-2601.
	Background- A number of observational studies examined the association between metformin therapy and ovarian cancer survival outcomes, but the results are inconsistent. Objective-To investigate the effect of metformin on survival for ovarian cancer patients. Method- PubMed, Embase and Web of Science databases were searched for relevant studies from the inception to June11, 2019. The strength of the relationship was assessed using summary hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Statistical analyses were carried out using random-effects model. Results-Totally, 6 retrospective cohort studies involving 2,638ovarian cancer patients were included. Metformin was notassociated with improved overall survival (HR=0.78,95% CI 0.54-1.12, P=0.175, I2= 61.6%)and disease-free survival (HR=0.49, 95% CI 0.20-1.17, P=0.106, I2=82.1%) in ovarian cancer patientscompared to non-metformin users. Conclusion-The current study provides preliminary evidence that metformin may not be associated with a survival benefit for ovarian cancer patients.More studieswith rigorous designs areneeded.

Wang, Y., et al. (2019). "Erxian decoction, a Chinese herbal formula, for menopausal syndrome: An updated systematic review." Journal of Ethnopharmacology 234: 8-20.
	Ethnopharmacological Relevance: Erxian decoction (EXD), a famous Chinese herbal prescription, consists of Rhizoma Curculiginis, Herba Epimedii, Radix Morindae Officinalis, Radix Angelicae Sinensis, Cortex Phellodendri, Rhizoma Anemarrhenae, all of which are recorded in the Chinese Pharmacopoeia.; Objective: To conduct an updated systematic and meta-analysis investigating efficacy and safety of EXD for menopausal syndrome.; Methods: An electronic search was conducted in eight databases from inception until July 2018. Randomized controlled trials with risk-of-bias score ≥ 7 according to the Cochrane Back Review Group were included for analyses. All participants with a diagnosis of menopausal syndrome met the established criteria. The treatment group was EXD monotherapy or adjunct therapy. Comparators were placebo, hormone replace therapy, hormone plus nonhormonal agents, nonhormonal agents and no treatment. The primary outcome measurements were the Kupperman index, total hot flush scores, total menopause rating scale (MRS) scores and total menopause-specific quality of life (MENQOL) scores. The secondary outcomes were total clinical effective rate, traditional Chinese medicine (TCM) syndrome scores, Hamilton depression (HAMD) scale scores, self-rating depression scale (SDS) scores, self-Rating Anxiety Scale (SAS) scores, athens insomnia scale (AIS) scores, serological indicators, blood pressure, and adverse events. RevMan 5.3 Software was used for data analyses. GRADE system was used to assess the level of evidence.; Results: Sixteen eligible studies with 1594 subjects were identified. Five studies showed EXD was contradictory results according to Kupperman index of menopausal syndrome compared with hormone. One study showed EXD significantly improved total hot flush scores, total MRS scores and total MENQOL scores compared with placebo (P < 0.05). Meta-analysis of 10 EXD monotherapy or 2 paratherapy studies showed that both can significantly improve total effective rate compared with hormone (P < 0.05); 3 studies showed that EXD plus hormone significantly reduces the TCM syndrome scores, HAMD scale scores, SDS scores and SAS scores compared with hormone (P < 0.05). One study showed a significant effect of EXD for reducing AIS scores compared with hormone (P < 0.05); 7 studies showed contradictory effects for improving serological indicators compared with hormone. Two studies reported adverse effects, whereas the other studies did not mention. The quality of the evidence of primary outcomes was moderate to high according to the GRADE profiler.; Conclusions: The present findings do not allow an assessment of the evidence because the low-quality studies included cannot be reproduced. However, we identified an area, which is worthy of further research. Rigorous RCTs are still needed in the future. (Copyright © 2019 Elsevier B.V. All rights reserved.)

Wang, Y., et al. (2019). "Clinicopathological and prognostic values of aldh1 in epithelial ovarian cancer: A meta-analysis." International Journal of Clinical and Experimental Medicine 12(9): 11049-11058.
	
Wang, Y., et al. (2023). "The efficacy of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer: A meta-analysis." European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 49(11): 106995.
	Background: Minimal invasive surgery (MIS) has been reported to increase the risk of cancer relapse and death compared with traditional open surgery in patients with early-stage cervical cancer (CC). Pre-operative conization is a protective procedure that as developed to reduce the risk caused by MIS.; Methods: Relevant publications were identified by searching medical databases prior to the December 31, 2022. The primary aim of this meta-analysis was to evaluate the efficacy of pre-operative conization on disease-free survival (DFS) in early-stage CC. The secondary objective was to assess the efficacy of pre-operative conization on overall survival (OS) in early-stage CC.; Results: Twelve studies were eligible for analysis. The pooled result of pre-operative conization showed a significantly improved DFS when compared with non-conization patients (HR, 0.28; 95% CI, 0.19-0.41), furthermore, pre-operative conization improved DFS by 75% (HR, 0.25; 95% CI, 0.13-0.46) in stage IB1 patients. In patients who underwent MIS, pre-operative conization also led to a significant improvement in DFS when compared with non-conization patients (HR, 0.21; 95% CI, 0.09-0.54). However, in patients who underwent pre-operative conization, MIS increased the risk of recurrence by 34% when compared with open abdominal radical hysterectomy (HR, 1.34; 95% CI, 0.41-4.38), although this difference was not statistically significant. Finally, the OS of early-stage CC was not significantly affected by surgical approach or conization.; Conclusion: Pre-operation conization represents a protective effect and can improve DFS when compared with non-conization in early-stage CC, especially in stage IB CC. There was no statistical evidence to indicate that pre-operation conization could improve OS. High-quality randomized controlled trials are required to verify these results.; Competing Interests: Declaration of competing interest All authors declare that they have no competing interests. (© 2023 Published by Elsevier Ltd.)

Wang, Y., et al. (2023). "Cost-utility analysis of a supervised exercise intervention for women with early-stage endometrial cancer." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 31(7): 391.
	Purpose: Cardiovascular disease (CVD) is the leading cause of death after treatment for endometrial cancer (EC). There is clinical evidence that exercise significantly reduces the risks of CVD and cancer recurrence in this population; however, it is unclear whether there is value for money in integrating exercise into cancer recovery care for women treated for EC. This paper assesses the long-term cost-effectiveness of a 12-week supervised exercise intervention, as compared with standard care, for women diagnosed with early-stage EC.; Method: A cost-utility analysis was conducted from the Australian health system perspective for a time horizon of 5 years. A Markov cohort model was designed with six mutually exclusive health states: (i) no CVD, (ii) post-stroke, (iii) post-coronary heart disease (CHD), (iv) post-heart failure, (v) post-cancer recurrence, and (vi) death. The model was populated using the best available evidence. Costs and quality-adjusted life years (QALYs) were discounted at 5% annual rate. Uncertainty in the results was explored using one-way and probabilistic sensitivity analyses (PSA).; Result: The incremental cost of supervised exercise versus standard care was AUD $358, and the incremental QALY was 0.0789, resulting in an incremental cost-effectiveness ratio (ICER) of AUD $5184 per QALY gained. The likelihood that the supervised exercise intervention was cost-effective at a willingness-to-pay threshold of AUD $50,000 per QALY was 99.5%.; Conclusion: This is the first economic evaluation of exercise after treatment for EC. The results suggest that exercise is cost-effective for Australian EC survivors. Given the compelling evidence, efforts could now focus on the implementation of exercise as part of cancer recovery care in Australia. (© 2023. The Author(s).)

Wang, Y., et al. (2019). "Multicentre, randomised controlled trial of adjuvant chemotherapy in cervical cancer with residual human papilloma virus DNA following primary radiotherapy or chemoradiotherapy: a study protocol." BMJ Open 9(10): e028171.
	Introduction: The role of adjuvant chemotherapy after radical radiotherapy (RT) or chemoradiotherapy (CRT) in cervical cancer awaits further confirmation. Evidences have shown that persistent human papilloma virus (HPV) DNA in exfoliated cell post-RT is a potential biomarker of subclinical residual disease and thus increases the risk of recurrence. In this prospective, multicentre, randomised controlled trial, we will use HPV DNA in exfoliated cell to identify patients with cervical cancer who received definitive RT or CRT with higher risk of relapse for adjuvant chemotherapy.; Methods and Analysis: Eligible patients with histologically confirmed cervical cancer stage IIA2 to IVA of the International Federation of Gynaecology and Obstetrics, adequate organ function and no locoregional disease or distant metastasis after completion of primary treatment will be screened for HPV DNA in exfoliated cell at 1 month post-RT. Patients with undetectable HPV DNA will undergo standard surveillance. Patients with detectable HPV DNA will be randomly assigned to either adjuvant chemotherapy with docetaxel and nedaplatin for four cycles (arm 1) or observation (arm 2). Patients will be stratified for primary treatment (RT vs CRT). The primary endpoint is relapse-free survival.; Ethics and Dissemination: This protocol received a favourable ethical opinion from the Ethics Committee of the Second Affiliated Hospital of Fujian Medical University on 6 February, 2018, (No. 28). The trial results will be published in peer-reviewed journals and presented in conferences. A summary of the findings will be made available to participants.; Trial Registration Number: ChiCTR-IIR-17012655; Pre-results.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Wang, Y., et al. (2021). "Safety and efficacy of vaginal laser therapy for stress urinary incontinence: a meta-analysis." Annals of Palliative Medicine 10(3): 2736-2746.
	Background: Laser therapy has recently been proposed as a novel treatment for stress urinary incontinence (SUI) due to offering several advantages. This study aimed to evaluate the safety and efficacy of laser treatment of SUI by a meta-analysis.; Methods: The systematic review registration number is INPLASY202080001. A comprehensive search to identify relevant studies was conducted using the PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases with a cutoff date of 1 November, 2020. Outcome measures were extracted based on subjective and objective indexes, including International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), and objective measurements "1-hour pad test" (1-hour test under standardized conditions). Score changes before and after treatment were evaluated through meta-analysis. Subgroup analysis was performed according to geographic region, type of urinary incontinence (UI), severity of UI, age, and body mass index (BMI).; Results: Sixteen published clinical research studies, involving 899 patients with SUI, were included in this study. After laser treatment, the change in the ICIQ-SF score at 1, 2, and 6 months was -5.49 (95% CI: -6.74--4.24; I2=91%, P<0.01), -4.97 (95% CI: -6.24--3.71), and -5.48 (95% CI: -6.15--4.81), respectively. The improvement in 1-hour pad weight test results at 1, 3, and 12 months post treatment was -5.59 (95% CI: -6.93--4.25), -4.96 (95% CI: -6.73--3.20), and -5.82 (95% CI: -6.77--4.87), respectively. The PISQ-12 score increased by 5.39 (95% CI: 1.20-9.58) following treatment. Subgroup analysis identified the type and severity of UI as the potential source of heterogeneity. Adverse effects were reported in 6 of the 16 trials and affected only a small number of patients. Most adverse events were mild or moderate and required no medical intervention or resolved in a few days.; Conclusions: Vaginal laser therapy appears to be a safe, effective, and minimally invasive treatment option for SUI that can be well tolerated by patients.

Wang, Y., et al. (2023). "The effect of myofascial therapy on postpartum rectus abdominis separation, low back and leg pain, pelvic floor dysfunction: A systematic review and meta-analysis." Medicine 102(44): e35761.
	Background: During pregnancy and postpartum, changes in biomechanics can cause dysfunctions in the myofascial system, such as rectus abdominis diastasis, various types of pain, and pelvic floor dysfunction. These common postpartum problems seriously threaten women's health. Myofascial therapy, as an effective means of improving biomechanics, has no unified understanding of its therapeutic effects on postpartum functional disorders. This study aims to systematically evaluate the rehabilitative effects of myofascial therapy on postpartum rectus abdominis diastasis, low back and leg pain, and pelvic floor dysfunction through a meta-analysis of published randomized controlled trials.; Methods: A systematic literature search of databases in Chinese and English was performed through May 2023. The treatment methods were randomized controlled studies using myofascial therapy in the treatment of rectus abdominis separation, lumbo-leg pain, and pelvic floor dysfunction. The main outcome indicators were abdominal circumference, rectus abdominis separation distance, visual analogue pain score, pelvic floor muscle potential, ability to live daily activities, number of events, and treatment effectiveness.; Results: There were 22 studies, including 2235 patients. The result showed that compared with control group, myofascial therapy demonstrated to reduce abdominal circumference and rectus abdominis separation index, improve lumbar function significantly, and decrease urinary incontinence and pelvic organ prolapse. In the myofascial therapy group, pelvic floor muscle strength was significantly enhanced, anterior/posterior resting potential of pelvic floor muscle was significantly decreased, and pelvic floor muscle potential was enhanced. Compared with the control group, the number of patients with various types of pain and pain scores were significantly reduced after myofascial therapy. When myofascial therapy lasted <4 weeks, pain relief was greater. In the myofascial therapy group, the ability to perform daily activities was significantly improved. An analysis of the effectiveness of the treatment showed that after myofascial therapy, the patient's symptoms improved significantly. There also saw low heterogeneity among all outcomes.; Conclusion: The results suggested that myofascial therapy could effectively reduce rectus abdominis separation, relieve pelvic floor muscle dysfunction, enhance lumbar function, relieve pain, and improve the ability of daily living activities. All the data demonstrated that myofascial therapy had a good therapeutic effect on postpartum dysfunction.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Wang, Z., et al. (2021). "The Effect of Lifestyle Intervention on Systemic Oxidative Stress in Women with Obesity and Infertility: A Post-Hoc Analysis of a Randomized Controlled Trial." Journal of Clinical Medicine 10(18).
	We aimed to study whether lifestyle intervention could reduce systemic oxidative stress (OS) and the association between OS and cardiometabolic outcomes in women with obesity and infertility. From 2009 to 2012, infertile women with a BMI ≥ 29 kg/m2 were randomly assigned to a six-month lifestyle intervention followed by infertility treatment (N = 289) or to prompt infertility treatment (N = 285). Fasting serum free thiols (FT) concentrations were determined by colorimetry at baseline, at three and six months after randomization. Generalized estimating equations and restricted cubic spline regressions were used to estimate mean differences in serum FT levels between groups and to explore associations between serum FT levels and cardiometabolic outcomes. Baseline serum FT levels did not differ between the two groups (N = 203 in the intervention group vs N = 226 in the control group, 222.1 ± 48.0 µM vs 229.9 ± 47.8 µM, p = 0.09). Body weight decreased by 3.70 kg in the intervention group compared with the control group at six months (95% confidence interval [CI]: -7.61 to 0.21, p = 0.06). No differences in serum FT levels were observed between groups at either three months (N = 142 vs N = 150, mean differences: -1.03 µM, 95% CI: -8.37 to 6.32, p = 0.78) or six months (N = 104 vs N = 96, mean differences: 2.19 µM, 95% CI: -5.90 to 10.28, p = 0.60). In a pooled analysis of all available measurements, triglycerides (crude B: 5.29, 95% CI: 1.08 to 9.50, p = 0.01), insulin (crude B: 0.62, 95% CI: 0.26 to 0.98, p = 0.001), and homeostasis model assessment of insulin resistance (crude B: 2.50, 95% CI: 1.16 to 3.38, p < 0.001) were positively associated with serum FT levels. High-sensitivity C-reactive protein (hs-CRP) was negatively associated with serum FT levels (crude B: -0.60, 95% CI: -1.11 to -0.10, p = 0.02). The change in hs-CRP during the lifestyle intervention was strongly and inversely associated with serum FT levels (crude B: -0.41, 95% CI: -0.70 to -0.13, p = 0.005). No significant deviations from linear associations were observed between serum FT and hs-CRP. We do not observe an improvement in systemic OS in women with obesity and infertility with modest weight loss. There were potential associations between OS and biomarkers of cardiometabolic health. Trial registration: This trial was registered on 16 November 2008 at the Dutch trial register (NTR1530).

Wang, Z., et al. (2021). "Effectiveness of a 6-Month Lifestyle Intervention on Diet, Physical Activity, Quality of Life, and Markers of Cardiometabolic Health in Women with PCOS and Obesity and Non-PCOS Obese Controls: One Size Fits All?" Nutrients 13(10).
	Little is known about the difference in effectiveness of lifestyle intervention between women with PCOS and non-PCOS women. In a post hoc longitudinal analysis of a randomized, controlled trial, we aimed to investigate whether infertile women with PCOS and obesity (N = 87) responded differently to a 6-month lifestyle intervention program than infertile non-PCOS obese controls (N = 172). We evaluated several aspects of the intervention such as changes in diet, physical activity, and dropout rate, as well as the effect on weight, quality of life (QoL), and cardiometabolic outcomes. Multilevel analyses were used, and analyses were adjusted for baseline characteristics such as age, education, and smoking. Although BMI in both groups significantly decreased at 3 months and 6 months, there were no significant differences between the groups at 3 months (adjusted B: -0.3, 95% CI: -0.9 to 0.3, p = 0.35) and 6 months (adjusted B: 0.5, 95% CI: -0.4 to 1.4, p = 0.29). Women with PCOS and non-PCOS women had similar compliance with the lifestyle intervention in terms of actual change in diet and physical activity. Mental QoL scores were not different at either 3 or 6 months. Physical QoL scores were lower in women with PCOS compared with non-PCOS women at 3 months (adjusted B: -2.4, 95% CI: -4.8 to -0.06, p = 0.045) but not at 6 months. Cardiometabolic parameters did not differ between the groups. Our results showed that infertile women with PCOS and obesity and non-PCOS obese controls responded largely similarly to our lifestyle intervention and achieved the same level of improvement in markers of cardiometabolic health.

Wang, Z., et al. (2022). "Efficacy and safety of oral kidney-tonifying Chinese patent medicines in treatment of postmenopausal osteoporosis: A network Meta-analysis." Chinese Traditional and Herbal Drugs 53(13): 4084-4099.
	Objective To evaluate the efficacy and safety of different kidney-tonifying Chinese patent medicines in the treatment of postmenopausal osteoporosis (PMOP) by network Meta-analysis. Methods Web of Science, Cochrane Library, Embase, PubMed, VIP, Wanfang, CNKI and Chinese Biomedical Literature Database (CBM) were searched by computer for randomized controlled trials (RCTs) on related kidney-tonifying Chinese patent medicines in the treatment of postmenopausal osteoporosis. The retrieval time was from the establishment of the database to November 2021. Studies that met the quality criteria were analyzed using Stata16.0 software and Review Manager 5.4. Results A total of 3246 articles were retrieved and finally 41 RCTs involving 13 interventions and 3699 patients were included. The results of network Meta-analysis showed that: In terms of improving effectiveness, the combination of Chinese patent medicine and conventional western medicine (CWM) was better than CWM or other Chinese patent medicine alone or the combination of both, and the safety of Chinese patent medicine alone was better. 1In terms of effective rate, the optimal first three interventions were Xianling Gubao Capsule () + CWM, Yougui Pill () + CWM, Lujiao Zhuanggu Capsule () + CWM; 2In terms of reducing VAS score, the optimal first three interventions were Lujiao Zhuanggu Capsule + CWM, Jiawei Erxian Granule () + CWM, Xianling Gubao Capsule + CWM; 3In terms of improving lumbar bone density, the optimal first three interventions were Gushukang Capsule () +CWM, Yougui Pill + CWM, Lujiao Zhuanggu Capsule + CWM; In terms of improving the bone density of the femoral neck, the optimal first three interventions were Gushukang Capsule + CWM, Lujiao Zhuanggu Capsule + CWM, Zhibai Dihuang Pill () + CWM; 5In terms of reducing serum osteocalcin, the optimal first three interventionss were Xianling Gubao + CWM, Zuogui Pill () + CWM, Qing'e Pill () + CWM; In terms of adverse reaction incidence, the safest top three treatment methods were Xianling Gubao Capsule, Xianling Gubao Capsule + CWM, Lujiao Zhuanggu Capsule+CWM. Conclusion The combination of kidney-tonifying Chinese patent medicines and CWM is better than single use in the treatment of PMOP. Each Chinese patent medicine has its own unique advantages, but the Chinese patent medicine with the effect of reinforcing tendons and bones was more effective. In terms of safety, Chinese patent medicine combined with or without CWM is superior to CWM, and Xianling Gubao Capsule may be the safest treatment method. Limited by the quality of the included studies, the conclusions obtained still need to be further verified.Copyright © 2022 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Wang, Z., et al. (2020). "The efficacy and safety of acupuncture for perimenopausal insomnia: A protocol for a network meta-analysis." Medicine 99(52): e23741.
	Background: As a common symptom of perimenopausal period, perimenopausal insomnia brings great pain to many women and families. Acupuncture has been accepted by people as the incidence rate of this disease increases. The purpose of this study is to systematically compare the safety and efficacy of various acupuncture treatments for perimenopausal insomnia through network meta-analysis.; Methods: We will search Web of Science, PubMed, The Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Date, VIP database, conference papers and grey literature. All relevant Randomized controlled trial (RCT) using acupuncture for perimenopausal insomnia will be included. Two reviewers will independently search and screen date. Network meta-analysis will be completed by Stata and WinBUGS software.; Results: This study will compare the efficacy and safety of different acupuncture treatments for perimenopausal insomnia.; Conclusion: The result of this study will provide reliable evidence for evaluating the efficacy and safety of acupuncture in the treatment of perimenpausal insomnia.; Inplasy Registration Number: INPLASY2020110047.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Wånggren, K., et al. (2022). "Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial." Human reproduction (Oxford, England) 37(10): 2366-2374.
	Study Question: Does supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate?; Summary Answer: Supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births.; What Is Known Already: Progesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited.; Study Design, Size, Duration: This is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate.; Participants/materials, Setting, Methods: Women, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer.; Main Results and the Role of Chance: There were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration.; Limitations, Reasons for Caution: The study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos.; Wider Implications of the Findings: Supplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine.; Study Funding/competing Interest(s): The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmö, Sweden. The authors have no personal conflicting interests to declare.; Trial Registration Number: NL4152.; Trial Registration Date: 5 December 2013.; Date of First Patient’s Enrolment: 18 February 2013. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Waqas, A., et al. (2023). "Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis." Global Mental Health 10: e22.
	Cognitive behavioral therapies (CBT) have been demonstrated efficacious in treating perinatal depression (PND). This has been demonstrated in several meta-analyses of randomized controlled trials and quasi-experimental studies. However, there is a need for up-to-date meta-analytical evidence providing reliable estimates for CBT's effectiveness in treating and preventing PND. Furthermore, with the world moving toward precision medicine, approaches require a critical synthesis of psychotherapies, especially to unpack their mechanisms of action and to understand what approaches work best for whom. Therefore, the present systematic review and meta-regression analyses aim to answer these research questions. We searched six academic databases through February 2022 and identified 56 studies for an in-depth review. Using pretested data extraction sheets, we extracted patient-level and intervention-level characteristics and effect size data from each study. Random-effects meta-analyses and mixed-effect subgroup analyses were run to delineate the effectiveness and moderators of CBT interventions for PND, respectively. CBT-based interventions yielded a strong effect size (SMD = -0.74, 95% confidence interval [CI]: -0.91 to -0.56, n = 9,722) in alleviating depressive symptoms. These interventions were effective across different delivery formats (individual, group, and electronic) and could be delivered effectively by specialists and nonspecialists. Longer duration CBT interventions may not necessarily be more effective than shorter ones. Moreover, CBT-based interventions should consider including various behavioral ingredients to maximize intervention benefits.Copyright © The Author(s), 2023. Published by Cambridge University Press.

Warne, E., et al. (2022). "Evaluating Group Psychological Interventions for Mental Health in Women with Infertility Undertaking Fertility Treatment: A Systematic Review and Meta-Analysis." Health psychology review: 1-45.
	We conducted a systematic review and meta-analysis of the published literature concerning the effectiveness of group psychological interventions in improving anxiety, depression, marital dissatisfaction, fertility quality of life and stress, and pregnancy outcomes of women with infertility, participating in fertility treatment. A search of five databases yielded 1603 studies; 30 articles met inclusion criteria, and computations of effect sizes ensued (Hedges' g and Odds Ratios (OR)). The total sample comprised 2752 participants, with 1279 participants receiving group intervention and 1473 participants in the comparison group. Group psychological interventions reduced depression (Hgw= -1.277; 95% CI = [-1.739- -0.815]; p= 0.000), anxiety (Hgw = -1.136, 95% CI [-1.527- -0.744]; p= 0.000), fertility stress (Hgw = -0.250, 95% CI [-0.388- -0.122]; p= 0.000), and marital dissatisfaction (Hgw = -0.938; 95% [CI -1.455- -0.421]; p= 0.000), and pregnancy rates improved (OR = 2.422 95% CI [2.037-2.879]; p = 0.000). No improvement was observed regarding fertility quality of life (Hgw = 0. 144; 95% CI [-0.176- 0.463]; p= 0.379). Our findings highlight that participation in group psychological intervention improved the mental health, fertility stress and pregnancy rates of women with infertility.

Wartena, R. and M. Matjila (2023). "Polycystic ovary syndrome and recurrent pregnancy loss, a review of literature." Frontiers in Endocrinology 14: 1183060.
	OBJECTIVE: PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of pregnancy loss in PCOS. However, uncertainty remains about their contribution to pregnancy loss and prognosis. This review of literature aims to identify what is known and what requires further investigation on the relationship between PCOS and recurrent pregnancy loss, to guide future research and optimize medical guidance throughout pregnancy. STUDY DESIGN: a review of literature was performed on several search engines using the following terms; polycystic ovarian syndrome, PCOS, recurrent pregnancy loss, recurrent miscarriage, RPL, aborted fetus, abortus provocatus, miscarriage and habitual abortion. RESULTS: 37 articles were included; 3 systematic reviews, 1 meta-analysis, 2 randomized controlled trials, 6 prospective cohort studies, 22 case-control studies and 3 case series. The main objectives investigated by studies were pregnancy complications, pregnancy loss and live birth in the PCOS population. CONCLUSION: Studies that investigated the relationship between PCOS and recurrent pregnancy loss are few and inconsistent and warrant further research. Factors apt for further investigation include the extent to which PCOS phenotypes, BMI, obesity, insulin resistance, hyperandrogenemia, SHBG, hs-CRP, CTRP6, adiponectin, plasma leptin, homocysteine, AMH and thrombophilia contribute to further risk of miscarriage. Other factors requiring further exploration in relation to risk for miscarriage in PCOS patient with RPL include sOB-R, PAI-Fx and the Factor-V-Leiden mutations.

Washington University, o. and M. Health National Institute of (2022). A Dyadic Approach to Perinatal Depression in Primary Care: Maternal Infant and Dyadic Care.
	No Results Available Behavioral: Promoting First Relationships-Brief|Behavioral: Perinatal Collaborative Care Change from Baseline in Perinatal Depression Symptomology on the Edinburgh Postnatal Depression Scale (EPDS)|Change from Baseline in Parental Self-Efficacy on the Self-Efficacy in a Nurturing Role (SENR)|Change from Postpartum Baseline in Dyadic Interaction|Change from Baseline in Disability on the World Health Organization Disability Assessment Schedule 2.0 (WHODAS)|Change from Postpartum Baseline in Maternal Functioning on the Barkin Index of Maternal Functioning (BIMF)|Relative utilization of MInD vs usual CC|Perceived match of treatment to patient need using Working Alliance Inventory (WAI-SR) Female Phase 2 60 Other|NIH Allocation: Randomized|Intervention Model: Parallel Assignment|Masking: Single (Outcomes Assessor)|Primary Purpose: Treatment STUDY00011405|1R34MH124798-01 June 1, 2025

Waterfield, A., et al. (2021). "Can effective supervised pelvic floor muscle training be provided by primary care nurses? A randomized controlled trial." International Urogynecology Journal 32(10): 2717-2725.
	INTRODUCTION AND HYPOTHESIS: To determine whether primary care nurses with no prior experience can, after training, provide effective supervised pelvic floor muscle training (PFMT) by a three-group parallel randomized controlled trial (RCT): primary care nurse, urogynaecology nurse specialist and controls undertaken in 11 primary care/general practices, covering urban and rural settings in SW England. The sample consisted of 337 women with weak pelvic floor muscles (Modified Oxford Score 2 or less) in a randomly sampled survey. METHODS: Following detailed instruction and training, primary care nurses recruited patients who were randomized to PFMT provided by them, a urogynaecology nurse specialist or a 'no training' control group. The primary outcome measure to assess the effectiveness of training was pelvic floor muscle strength as measured by perineometry. RESULTS: Two hundred forty women aged 19 to 76 (median 49) years were recruited. After 3 months there was an increase in strength in both intervention groups compared with controls: median differences (95% CI) were 3.0 (0.3, 6.0) cmH2O higher for the primary care nurse group (n = 50) compared to the control group (n = 56; p = 0.02) and 4.3 (1.0, 7.3) cmH2O for the urogynaecology nurse specialist group (n = 53) compared to control (p < 0.01); there was no difference between the primary care nurse and urogynaecology nurse specialist groups [1.3 (-2.0,4.7; p = 0.70]. CONCLUSIONS: PFMT provided by trained primary care nurses achieved improvements in pelvic floor muscle strength compared with controls (and comparable to that of a urogynaecology nurse specialist). This could have implications for the provision of PFMT for all women and potentially help in the prevention of pelvic floor dysfunction. TRIAL REGISTRATION: Registered with ClinicalTrials.gov; Identifier NCT01635894. This was done retrospectively to conform to current registration requirements. When the trial commenced (2003), there was no requirement to register; this was introduced in 2005. The International Committee of Medical Journal Editors (ICMJE) decided that from July 1, 2005, no trials would be considered for publication unless they are included on a clinical trials registry, hence the retrospective registration.

Watson, C. H., et al. (2022). "Reducing non-surgical readmissions on a gynecologic oncology service." Gynecologic Oncology 165(1): 4-10.
	Objective: To assess the effects of a quality improvement (QI) initiative designed to reduce non-surgical readmissions on a gynecologic oncology service. Method(s): A two-phase QI initiative was implemented on an inpatient gynecologic oncology service to reduce non-surgical 30-day readmissions. Phase 1, from July 2018 to June 2020, included trainee education, frequent physical therapy consultation, pharmacy discharge medication review, 72-h post-discharge telephone call, and standardized 10-day clinic follow-up after discharge. Phase 2, from July 2020 to December 2020, incorporated a nurse practitioner to perform discharge navigation and arrange outpatient follow-up. The incidence of non-surgical readmissions during these phases was compared to that of a baseline period (July 2017-June 2018). We also assessed readmissions to identify common indications and evaluate potential demographic and clinical risk factors. Result(s): Of 390 total non-surgical gynecologic oncology admissions, 100 were readmitted within 30 days (25.6%). Gastrointestinal tract (GI) obstruction, malignancy-associated pain and infection were the most common symptomatic diagnoses at the index admission, and 30% of readmitted patients had an identical indication for readmission. Compared to the baseline period, we observed a reduction in non-surgical readmissions from 34.1% to 22.6% in Phase 1 and to 18.9% in Phase 2 (p < 0.03) based on internal review, and a reduction from 13.9% to 11.9% in Phase 1 and to 4.7% in Phase 2 (p = 0.04) based on healthcare performance tracking data. Conclusion(s): 30-day hospital readmission among non-surgical gynecologic oncology patients is common. Implementation of a multifaceted readmissions reduction QI initiative significantly improved readmission rates.Copyright © 2022 Elsevier Inc.

Watson, H. A., et al. (2021). "Evaluating the use of the QUiPP app and its impact on the management of threatened preterm labour: a cluster randomised trial." PLoS Medicine 18(7): e1003689.
	BACKGROUND: Preterm delivery (before 37 weeks of gestation) is the single most important contributor to neonatal death and morbidity, with lifelong repercussions. However, the majority of women who present with preterm labour (PTL) symptoms do not deliver imminently. Accurate prediction of PTL is needed in order ensure correct management of those most at risk of preterm birth (PTB) and to prevent the maternal and fetal risks incurred by unnecessary interventions given to the majority. The QUantitative Innovation in Predicting Preterm birth (QUIPP) app aims to support clinical decision‐making about women in threatened preterm labour (TPTL) by combining quantitative fetal fibronectin (qfFN) values, cervical length (CL), and significant PTB risk factors to create an individualised percentage risk of delivery. CONCLUSIONS: This cluster randomised trial did not demonstrate that the use of the QUiPP app reduced unnecessary management of TPTL compared to current management but would safely improve the management recommended by the National Institute for Health and Care Excellence (NICE). Interpretation of qfFN, with or without the QUiPP app, is a safe and accurate method for identifying women most likely to benefit from PTL interventions. TRIAL REGISTRATION: ISRCTN Registry ISRCTN17846337. METHODS AND FINDINGS: EQUIPTT was a multi‐centre cluster randomised controlled trial (RCT) involving 13 maternity units in South and Eastern England (United Kingdom) between March 2018 and February 2019. Pregnant women (n = 1,872) between 23+0 and 34+6 weeks' gestation with symptoms of PTL in the analysis period were assigned to either the intervention (762) or control (1,111). The mean age of the study population was 30.2 (+/‐ SD 5.93). A total of 56.0% were white, 19.6% were black, 14.2% were Asian, and 10.2% were of other ethnicities. The intervention was the use of the QUiPP app with admission, antenatal corticosteroids (ACSs), and transfer advised for women with a QUiPP risk of delivery >5% within 7 days. Control sites continued with their conventional management of TPTL. Unnecessary management for TPTL was a composite primary outcome defined by the sum of unnecessary admission decisions (admitted and delivery interval >7 days or not admitted and delivery interval ≤7 days) and the number of unnecessary in utero transfer (IUT) decisions/actions (IUT that occurred or were attempted >7 days prior to delivery) and ex utero transfers (EUTs) that should have been in utero (attempted and not attempted). Unnecessary management of TPTL was 11.3% (84/741) at the intervention sites versus 11.5% (126/1094) at control sites (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.66‐1.42, p = 0.883). Control sites frequently used qfFN and did not follow UK national guidance, which recommends routine treatment below 30 weeks without testing. Unnecessary management largely consisted of unnecessary admissions which were similar at intervention and control sites (10.7% versus 10.8% of all visits). In terms of adverse outcomes for women in TPTL <36 weeks, 4 women from the intervention sites and 12 from the control sites did not receive recommended management. If the QUiPP percentage risk was used as per protocol, unnecessary management would have been 7.4% (43/578) versus 9.9% (134/1,351) (OR 0.72, 95% CI 0.45‐1.16). Our external validation of the QUiPP app confirmed that it was highly predictive of delivery in 7 days; receiver operating curve area was 0.90 (95% CI 0.85‐0.95) for symptomatic women. Study limitations included a lack of compliance with national guidance at the control sites and difficulties in implementation of the QUiPP app.

Wattanayingcharoenchai, R., et al. (2021). "Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis." BJOG : an international journal of obstetrics and gynaecology 128(1): 25-35.
	Background: The efficacy of hormonal regimens for the prevention of endometrioma recurrence in women who have undergone conservative surgery is still controversial.; Objective: To compare the efficacy of different hormonal regimens in this context and to rank them.; Search Strategy: MEDLINE and Scopus databases were searched through January 2020.; Selection Criteria: Randomised controlled trials (RCTs) or cohorts, comparing the effect of any pair of interventions (i.e. cyclic oral contraceptives [OC], continuous OC, gonadotropin-releasing hormone agonist [GnRHa], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNG-IUS] and expectant management) on endometrioma recurrence were selected.; Data Collection and Analysis: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA) and ranked in descending order.; Main Results: Six RCTs (675 patients) and 16 cohorts (3089 patients) were included. NMA of the RCTs involving expectant management, cyclic OC, continuous OC, GnRHa and GnRHa + LNG-IUS, showed that all hormonal regimens had a nonsignificant lower risk of endometrioma recurrence compared with expectant management. NMA of the cohorts involving expectant, cyclic OC, continuous OC, GnRHa, DNG, LNG-IUS, GnRHa + OC, and GnRHa + LNG-IUS indicated that LNG-IUS, DNG, continuous OC, GnRHa + OC and cyclic OC had a significantly lower risk of endometrioma recurrence than expectant management. LNG-IUS was ranked highest, followed by DNG and GnRHa + LNG-IUS. Long-term use of hormonal treatment either OC or progestin had a significantly lower risk of endometrioma recurrence than expectant treatment.; Conclusion: In the NMA of RCTs, there was no evidence supporting hormonal treatment for postoperative prevention of endometrioma recurrence. This was at odds with the cohort evidence, which found the protective effect of OC and progestin regimens, especially long-term treatment. Large-scale RCTs of these agents are still required.; Tweetable Abstract: Hormonal regimens given as long-term treatment tend to reduce risk of endometrioma recurrence after conservative surgery. (© 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Weaver, K. E., et al. (2023). "Effectiveness of a cardiovascular health EHR application for cancer survivors in community oncology practice: Results from WF-1804CD." Journal of Clinical Oncology 41(17 Supplement).
	Background: Practice guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. The Automated Heart-Health Assessment study (AH-HA: WF-1804CD, NCT# 03935282) evaluated a novel electronic health record (EHR) clinical decision support tool based on American Heart Association Simple 7 cardiovascular health (CVH) factors to promote provider-patient CVH discussions in outpatient oncology. Method(s): This clinic-randomized trial (R01CA226078), coordinated by the Wake Forest NCORP Research Base (UG1CA189824), randomized NCORP oncology practices using the Epic EHR to the AH-HA tool or usual care and enrolled survivors receiving routine care at least 6 months post-curative cancer treatment. The tool rendered an interactive display of risk factors, automatically populated from the EHR, alongside a tab indicating receipt of cancer treatments with cardiotoxic potential. Survivors at AH-HA sites had tool access during a routine visit; survivors at usual care sites did not. Immediately post-visit, each survivor was asked about counseling on 7 CVH factors [body mass index, physical activity, diet, smoking status, blood pressure, cholesterol, and glucose]. The primary endpoint is survivor-reported discussion of non-ideal or missing CVH factors; with 8 randomized practices (ICC=0.03), the study design had 82% power to detect a difference of 20% reported discussions in usual care versus 40% in AH-HA. Additional clinical endpoints were documentation of CVH discussions, referrals to primary care and cardiology, and change in CVH factors over 12 months (ongoing). A mixed effects logistic regression model assessed the effect of AH-HA on CVH discussions between the arms, with study arm as a fixed effect and practice as a random effect. Result(s): 5 usual care and 4 AH-HA practices enrolled 645 survivors from 10/1/2020- 2/28/2023. The majority had breast cancer (82%; 8% endometrial, 5% colorectal, 5% prostate, lymphoma or multiple types). Most survivors were female (96%; 84% White/non-Hispanic, 8% Black; 3% Hispanic; mean age= 62 yrs and median time since diagnosis=3.6 yrs). 18 participants (3%) did not complete necessary assessments, leaving 627 evaluable. 87% of providers (n=15) rated the tool utility and ease of use positively. Conclusion(s): The AH-HA tool was acceptable and effective at promoting CVH discussions during routine follow-up care for survivors and referrals to primary care.

Webb, L. (2021). "Probiotics for preventing recurrent bacterial vaginosis." JAAPA : official journal of the American Academy of Physician Assistants 34(2): 19-22.
	Abstract: Multiple studies have shown that oral or vaginal probiotics can effectively treat and prevent recurrent bacterial vaginosis. The dose, route, and treatment protocols vary greatly between studies, but many have shown a statistically significant reduction in the rate of recurrence of bacterial vaginosis. Further research is needed to determine the adequate dose, specific probiotic, optimal duration, and route of administration, with or without antibiotics. (Copyright © 2021 American Academy of Physician Assistants.)

Wei, H., et al. (2023). "Levonorgestrel-releasing intrauterine system-based therapies for early-stage endometrial cancer: a systematic review and meta-analysis." Journal of Gynecologic Oncology 34(2): e36.
	Objective: To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens.; Methods: The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate.; Results: A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%-73.2%), with 29.6% (95% CI=23.3%-36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m² who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%-88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%-53.9%) and 39.3% (95% CI=24.0%-57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups.; Conclusion: LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.; Trial Registration: PROSPERO Identifier: CRD42022352890.; Competing Interests: No potential conflict of interest relevant to this article was reported. (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Wei, J., et al. (2019). "Meta analysis of the efficacy of pelvic floor myoelectric stimulation in the treatment of urination dysfunction." 中国循证医学杂志 19(4): 424-429.
	Objective To systematically evaluate the effect of pelvic floor myostimulation in the treatment of urination dysfunction. Methods Computer retrieves PubMed, EmBase, The Cochrane Library, CBM, CNKI, VIP and WANFANG Data Databases. The time limits were built to August 2018. After independently screening literature, extracting information and evaluating the risk of bias in the study, Meta analysis was conducted using the RevMan 5.3 software. The results were finally included in 9 RCTs in a total of 559 patients.Meta analysis results showed: before and after bladder capacity in pelvic floor electrostimulation therapy patients Difference [MD=79.25,95% CI (40.36,118.15), P≈ 0.000 1], residual urine margin [MD=35.50,95% CI (7.60,63.41), P=0.01], maximum forced urinary muscle pressure before and after [MD=5.19,95% CI (2.11,8.27), P≈ 0.001], number of urinary leakage [R= 1.95,95% CI (1.39,2.52), P¥0.000 01], before and after the average daily urination rate [RR=2.64,95% CI (1.97,3.31), P¥0.000 01], International lower urinary tract symptom score [MD=5.07,95% CI (2.17,7.96), P=0.000 6] Conclusions Current evidence shows that pelvic floor myostimulation can be effective in improving urination dysfunction in patients, subject to the number and quality of inclusion studies, which are yet to be validated by more high-quality studies.

Wei, K., et al. (2022). "Probiotics, a Promising Therapy to Reduce the Recurrence of Bacterial Vaginosis? A Systematic Review and Meta Analysis." PROSPERO International prospective register of systematic reviews.
	
Wei, W., et al. (2022). "Effect of ovarian endometriosis cystectomy on ovarian reserve and assisted reproductive technology outcome: a systematic review and meta-analysis."
	
Weidlinger, S., et al. (2021). "Sustainability of vaginal estrogens for genitourinary syndrome of menopause - a systematic review." Climacteric : the journal of the International Menopause Society 24(6): 551-559.
	Genitourinary syndrome of menopause (GSM) is a highly prevalent, not self-limiting condition displaying a major negative impact on sexual function and emotional well-being. Various non-hormonal and hormonal treatment options are available. Many women consider GSM treatment to be a short-term interval cure rather than a long-term or lifelong treatment. The aim of this systematic literature search was to assess the sustainability of vaginal estrogens for GSM treatment after treatment cessation. We found that objective GSM signs mostly deteriorated within approximately 4 weeks after vaginal estrogen treatment cessation, while vaginal estrogens had a more sustainable impact on subjective GSM symptoms up to 3-6 months. However, overall, scientific evidence on sustainability of vaginal estrogens was low. Thus, GSM treatment should not be considered a short-term interval cure but long-term therapy. Further studies in an internationally harmonized setting (Core Outcomes in Menopause [COMMA]) are needed.

Weihe, L., et al. (2023). "Comparison of ovarian reserve at different time points after laparoscopic cystectomy in patients with ovarian endometriosis differ in cyst size: a systematic review and meta-analysis."
	
Weinberger James, M., et al. (2019). "Female Sexual Dysfunction: A Systematic Review of Outcomes Across Various Treatment Modalities." Sexual Medicine Reviews 7(2): 223-250.
	Background: Female sexual dysfunction (FSD) is a highly prevalent condition. Nevertheless, the scientific literature has only recently begun to accumulate evidence for treatment modalities that address the underlying etiologies of FSD.; Aim: The purpose of this systematic review is to elucidate what treatments are effective across the various symptom complexes of FSD.; Methods: Utilizing Meta-analysis of Observational Studies in Epidemiology guidelines, we conducted a systematic review of PubMed, EMBASE, clinicaltrials.gov, and the Cochrane Review databases. Eleven search strings, encompassing the terms "female sexual dysfunction" and "treatment," in combination with "vulvovaginal atrophy," "vaginismus," "vaginal atrophy," "vulvodynia," "vestibulitis," "hypoactive sexual desire," "arousal disorder," "sexual pain disorder," "genitourinary syndrome of menopause," and "orgasmic disorder" were utilized. 605 Relevant articles were retrieved. A total of 103 original studies met inclusion criteria.; Outcomes: We assess peer-reviewed literature.; Results: 42 Treatment modalities were utilized, including 26 different classes of medications. Although outcome measures varied, the most substantial improvement across multiple studies was noted with various hormonal regimens. The most common treatments included hormonal therapy (25 studies), phosphodiesterase type-5 inhibitors (9 studies), botulinum toxin A (5 studies), and flibanserin (5 studies). The psychotherapeutic approach was detailed in 36 articles while 3 studies utilized homeopathic treatments. Numerous treatments showed efficacy in a single case series, including the promising results associated with the micro-ablative carbon-dioxide laser. Despite the marked improvement in specific FSD domains, neither pharmacologic treatments nor psychotherapeutic interventions demonstrate consistent disease resolution.; Conclusions: Treatment of FSD is multi-factorial; medications alone do not resolve FSD. The wide variability of treatment and outcome measures across the literature attests to the complexity of FSD and the need for a treatment algorithm that addresses all 4 domains of FSD. Weinberger JM, Houman J, Caron AT, et al. Female Sexual Dysfunction: A Systematic Review of Outcomes Across Various Treatment Modalities. Sex Med Rev 2019;7:223-250. (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Weiner, E., et al. (2023). "Virtual Prenatal Care: the Effect of Telemedicine and Home-Ultrasound on Maternal Anxiety and Attachment during Pregnancy in Women with a History of Pregnancy Loss." Obstetrics and Gynecology 141(5): 81S.
	INTRODUCTION: We aimed to study the effects of twice‐a‐week telemedicine visits on maternal anxiety and antenatal attachment in women with a history of previous pregnancy loss by complementing routine prenatal care with home ultrasound. METHODS: This was a randomized controlled trial. Women with history of pregnancy loss (.20 weeks) were recruited and randomized 1:1 in the treatment arms early in their subsequent pregnancy in our high‐risk clinic. The control group received routine prenatal high‐risk care per protocol, while the study group received additional twice‐a‐week telemedicine visits with a maternal‐fetal medicine specialist, which included a home ultrasound scan (for fetal heart rate, movement, and amniotic fluid) for reassurance. The scan was performed by the patient using a home ultrasound device (Pulsenmore ES) with physician authorization and guidance. Maternal anxiety was evaluated by the validated State‐Trait Anxiety Inventory Scale (STAI‐S) and maternal attachment was evaluated by the validated Maternal Antenatal Attachment Scale (MAAS‐2) at four time points throughout pregnancy. The primary outcome was the STAI‐S score at the last prenatal visit. Power analysis required 40 patients to demonstrate a 20% difference in the primary outcome. The study was approved by the local IRB, and all patients signed an informed consent upon randomization. RESULTS: To date, 32 patients completed follow‐up, with 16 per arm. There were no differences in demographics or pregnancy outcomes between groups. The study group demonstrated lower anxiety levels at the last prenatal visit (STAI 42.264.7 versus 49.665.8, P,.001), higher differences between STAI scores at the first versus last visit (29.962.7 versus 27.163.1, P 5.011), and higher MAAS‐2 scores (50.463.9 versus 47.264.5, P 5.039) at last visit. CONCLUSION: Routine prenatal telemedicine visits with home ultrasound can lower maternal anxiety and improve attachment in women with previous pregnancy loss.

Weinstein, M. M., et al. (2022). "Digital Therapeutic Device for Urinary Incontinence: A Randomized Controlled Trial." Obstetrical and Gynecological Survey 77(7): 406-407.
	
Weinstein, M. M., et al. (2023). "Digital Therapeutic Device for Urinary Incontinence: A Longitudinal Analysis at 6 and 12 Months." Obstetrics and Gynecology 141(1): 199-206.
	OBJECTIVE: To evaluate the long-term efficacy of an 8-week regimen of pelvic floor muscle training guided by a motion-based digital therapeutic device compared with a standard home program in the treatment of stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI). METHOD(S): The primary virtual trial was conducted from October 2020 to March 2021; 363 women with SUI or stress-predominant MUI were randomized to complete pelvic floor muscle training using the device (intervention group) or a standard home pelvic floor muscle training program (control group) for 8 weeks. Primary outcomes included change in UDI-6 (Urogenital Distress Inventory, Short Form) score and SUI episodes on a 3-day bladder diary. The PGI-I (Patient Global Impression of Improvement) was also assessed, with "much better"and "very much better"responses considered as improvement. In this planned secondary analysis, symptom and adherence data were collected in follow-up at 6 and 12 months. A modified intention-to-treat analysis was performed using Student's t tests and chi2 tests as appropriate. RESULT(S): Of 299 participants analyzed at 8 weeks, 286 (95.7%) returned 6- and 12-month data (151 in the control group, 135 in the intervention group). Mean age was 51.9+/-12.8 years, and mean body mass index (BMI) was 31.8+/-7.4; 84.6% of participants were parous, and 54.9% were postmenopausal. Mean change in UDI-6 score from baseline to 6 and 12 months was significantly greater in the intervention group than in the control group (20.2+/-20.9 vs 14.8+/-19.5, P=.03 and 22.7+/-23.3 vs 15.9+/-20.3, P=.01, respectively). Participants in the intervention group had more than twice the odds of reporting improvement on the PGI-I compared with participants in the control group (OR 2.45, 95% CI 1.49-4.00). CONCLUSION(S): Pelvic floor muscle training guided by a motion-based digital therapeutic device yielded significantly greater urinary incontinence symptom improvement compared with a standard home pelvic floor muscle training program at 6 and 12 months, although continued improvement waned over time. This technology may facilitate pelvic floor muscle training access and adherence for women with SUI and stress-predominant MUI and represents an effective modality for scaling first-line care. FUNDING SOURCE: Renovia Inc. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov, NCT04508153.Copyright © 2022 The Author(s).

Weinstein, M. M., et al. (2021). "Randomized trial comparing efficacy of pelvic floor muscle training with a digital therapeutic motion-based device to standard pelvic floor exercises for treatment of stress urinary incontinence (SUV trial): An all-virtual trial design." Contemporary Clinical Trials 105: 106406.
	OBJECTIVE: To compare the efficacy of an Intravaginal Motion-Based Digital Health System (PDHS) compared to standardized Pelvic Floor Muscle Training (PFMT) for the treatment of stress or stress-predominant urinary incontinence (SUI). METHODS: This is a virtually conducted prospective randomized controlled trial. The primary outcomes are change in urinary incontinence episodes by 3-day bladder diary and change in Urogenital Distress Inventory-6 score, measured at 8 weeks. Secondary outcomes include: Patient Global Impression of Severity (PGI-S), PGI-Improvement (PGI-I), Pelvic Floor Distress Inventory-20(PFDI-20), Pelvic Floor Impact Questionnaire-7(PFIQ-7), Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-IR), Short Form-2 (SF-20), and assessment of adverse event (AE). Subjects are randomized 1:1 to an intervention group using leva PDHS for PFMT or a control group, using a home Kegel exercise program. Sample size needed to identify a 60% difference in incontinence episodes from baseline to 8 weeks post-randomization using alpha = 0.05, and a power of 0.8 is 156 subjects. To identify a 30% difference in the UDI-6 score from Baseline to Week 8 (alpha = 0.05, power = 0.8, using a one-tailed t-test) the needed sample size is 278, and allowing for an attrition rate of 15%, will require approximately 350 subjects, providing power to detect differences in both primary outcomes. RESULTS: Recruitment was initiated September 2020 and is on target to date. The trial is projected to be complete in 2021and is registered at clinicaltrials.govNCT04508153. CONCLUSION: This novel virtual recruitment approach may provide more efficient recruitment of large numbers of subjects and provide input into the use of app-based management of pelvic floor interventions.

Weis Carol, A., et al. (2020). "Chiropractic Care of Adults With Postpartum-Related Low Back, Pelvic Girdle, or Combination Pain: A Systematic Review." Journal of manipulative and physiological therapeutics 43(7): 732-743.
	Objective: The purpose of this study was to conduct a systematic review (SR) of the literature to assess the effectiveness of specific chiropractic care options commonly used for postpartum low back pain (LBP), pelvic girdle pain (PGP), or combination (LBP and PGP) pain.; Methods: A search strategy was developed. Interventions were those manual or other nonpharmacologic therapies commonly used by chiropractors (not requiring additional certifications). The outcomes were self-reported changes in pain or disability self-reported outcomes. We used the Scottish Intercollegiate Guideline Network checklists. Strength of the evidence (excluding cohort studies) was determined using an adapted version of the US Preventive Services Task Force criteria as described in the UK report.; Results: Of the 1611 published articles, 16 were included. These were 5 SRs, 10 randomized controlled trials (RCTs), and 1 cohort study. Postpartum LBP (1 RCT): moderate, favorable strength for spinal manipulation therapy/mobilization. Postpartum PGP (4 RCTs): moderate, unclear strength for exercise; and inconclusive, unclear strength for patient education. Postpartum LBP or PGP (3 SRs and 4 RCTs): inconclusive, unclear strength for exercise, self-management, and physiotherapy; while osteopathic manipulative therapy was inconclusive, favorable.; Conclusion: No treatment option was identified as having sufficient evidence to make a clear recommendation. This SR identified a scarcity of literature regarding chiropractic care and back pain for postpartum women, as well as inconsistency among the terms LBP, PGP, and combination pain. (Copyright © 2020. Published by Elsevier Inc.)

Weis Carol, A., et al. (2020). "Chiropractic Care for Adults With Pregnancy-Related Low Back, Pelvic Girdle Pain, or Combination Pain: A Systematic Review." Journal of manipulative and physiological therapeutics 43(7): 714-731.
	Objective: The purpose of this study was to conduct a systematic review (SR) of the literature to assess the effectiveness of chiropractic care options commonly used for pregnancy-related low back pain (LBP), pelvic girdle pain (PGP), or combination pain for both experienced practitioners and students of chiropractic.; Methods: We included procedures that were commonly used by chiropractors and not requiring additional certifications. Outcomes were self-reported changes in pain or disability. We used the Scottish Intercollegiate Guideline Network checklists to assess outcomes. For strength of evidence, we used the adapted version of the US Preventive Services Task Force criteria as described in the UK report.; Results: Fifty articles were included from 18 SRs, 30 randomized controlled trials (RCTs), and 2 cohort studies. Pregnancy LBP (7 SRs and 12 RCTs): moderate, favorable evidence for electrotherapy and osteopathic manipulative therapy; inconclusive, favorable strength for chiropractic care, exercise, and support devices; and inconclusive, unclear strength for spinal manipulative therapy. Pregnancy PGP (4 SRs and 4 RCTs): inconclusive, favorable strength for exercise; and inconclusive, unclear evidence for patient education, information, and support devices. Pregnancy LBP or PGP (13 SRs and 12 RCTs): moderate, unclear evidence for complementary and alternative medicine; moderate, unclear evidence for exercise; inconclusive, favorable evidence for multimodal care, patient education, and physiotherapy; and inconclusive, unclear strength for spinal manipulative therapy, osteopathic manipulative therapy, and support devices.; Conclusion: Although there is a lack of conclusive evidence, many of the interventions have moderate or unclear but favorable evidence. (Copyright © 2020. Published by Elsevier Inc.)

weisen, f., et al. (2021). "Reduction of ovarian dysfunction in laparoscopic Water separation stripping for ovarian endometriosis: meta-analysis and systematic review."
	
Weiting, L., et al. (2021). "Efficacy and safety of acupuncture and or moxibustion for managing primary dysmenorrhea: a systematic review protocol of randomised controlled trials."
	
Wen, J., et al. (2021). "Acupuncture Medical Therapy and its Underlying Mechanisms: A Systematic Review." American Journal of Chinese Medicine 49(1): 1-23.
	As a traditional Chinese alternative health care approach, acupuncture is gaining increasing attention and reputation in China and overseas. While becoming increasingly popular globally, some consumers and professionals still know little about the therapy and underlying mechanisms of acupuncture. Due to local superiority, there are large numbers of both clinical applications and mechanistic studies performed in China compared to countries overseas. Herein, this review attempts to give a comprehensive profile of the development, application, and mechanisms of acupuncture in treating major diseases. The number of clinical publications concerning acupuncture-treated neurological diseases, endocrine and metabolic diseases, circulatory diseases, respiratory diseases, etc. is first counted, and then, the application and therapeutic mechanisms of acupuncture on the predominant diseases in each category, including obesity, facial paralysis, sciatica, depression, hypertension, asthma, etc., are specifically discussed in this paper. The evolution of acupuncture tools and the rationality of acupoints are also discussed. This review not only summarizes the mechanisms of acupuncture but also provides useful information, such as specific acupoints and acupuncture procedures, for treating common diseases. Therefore, the current study provides useful information for both investigators and acupuncturists.Copyright © 2021 World Scientific Publishing Company.

Wen, Z., et al. (2021). "A network meta-analysis of the optimal choice of treatment strategies for FIGO stage IB2-IIA cervical cancer."
	
Wenbin, M., et al. (2022). "Add-on effect of Guizhi Fuling Formula for treating infertility induced by polycystic ovary syndrome: a meta-analysis of randomized controlled trials."
	
Wendel, M. P. and E. F. Magann (2022). "The Impact of Adenomyosis on Pregnancy and Pregnancy Outcomes: A Review." Obstetrical & gynecological survey 77(8): 495-500.
	OBJECTIVE: The aim of this review was to describe the risk factors, diagnosis, and effects on pregnancy of the gynecologic condition adenomyosis. METHODS: A PubMed, Web of Science, and CINAHL search was undertaken. Citations were limited to the past 30 years. RESULTS: There were 223 articles identified, with 31 articles being the basis of this review. Adenomyosis is a relatively common gynecologic condition that was previously thought to predominantly occur in older women, as it was diagnosed most commonly after a hysterectomy. As imaging techniques have advanced, this condition is now able to be diagnosed much earlier in life and is estimated to affect up to 20% of reproductive aged women. As studies have followed these women through subsequent pregnancies, an increased risk of adverse pregnancy outcomes has been observed. These include miscarriage, preterm birth, preterm prelabor rupture of membranes, small for gestational age, low birthweight, and preeclampsia, among others. This review is to examine the incidence, risk factors, and diagnostic criteria of adenomyosis and to then discuss its role in adverse pregnancy outcomes. CONCLUSIONS: Adenomyosis has been predominately a gynecologic condition, but now has been shown to adversely affect pregnancy outcomes. Diagnosis is made with histology, but may be suspected based on magnetic resonance imaging and ultrasound findings. Despite evidence of adverse pregnancy outcomes, there are no established strategies to risk, stratify, or prevent any of these outcomes.

Wenham, R., et al. (2023). "A multicenter, open-label phase 1/2 trial evaluating the safety, tolerability, and efficacy of MORAb202, a folate-receptor-alpha-targeting antibody-drug conjugate in patients with selected tumor types." Cancer Research 83(8 Supplement).
	Background: MORAb-202 (farletuzumab ecteribulin) is an antibody-drug conjugate (ADC) comprised of the humanized antifolate receptor-alpha (FRalpha) monoclonal antibody, farletuzumab, and the cytotoxic microtubule inhibitor, eribulin, conjugated by a cathepsin B-cleavable linker. MORAb-202 targets the eribulin payload to tumor cells expressing FRalpha, where internalization leads to lysosomal cleavage of the ADC and intracellular release of eribulin, causing apoptosis, cell-cycle arrest, and bystander effects in adjacent cells. A previous phase 1 study in Japan of MORAb-202 (NCT03386942) demonstrated antitumor activity across multiple tumor types and identified interstitial lung disease (ILD) as an adverse event of interest (Shimizu CCR 2021). An expansion cohort (doses: 0.9, 1.2 mg/kg) in patients with platinum-resistant ovarian cancer (OC) found meaningful efficacy across FRalpha-expression levels and ILD/pneumonitis (mainly low grade) was the most common adverse event (Nishio ASCO 2022). Method(s): This multicenter phase 1/2 study (NCT04300556) consists of Dose-Escalation and DoseConfirmation cohorts. In the Dose-Escalation phase, the primary objectives were to evaluate safety/tolerability and determine the recommended phase 2 dose of MORAb-202 in patients with OC, endometrial cancer (EC), non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC). In the ongoing Dose-Confirmation phase, the primary objectives are (1) to further evaluate safety/tolerability and (2) to evaluate preliminary efficacy (Objective Response Rate) in patients with OC or EC. Based on a population pharmacokinetics model (Hayato ASCO 2022), body-surfacearea-based dosing is utilized. The initial cohort has enrolled 7 patients at a MORAb-202 25 mg/m2 IV Q3W dose and is ongoing; further enrollment of patients at 25 mg/m2 and 33 mg/m2 will occur following ILD safety evaluation. Tumor assessments will be conducted by investigators using RECIST v1.1 at screening, every 6 weeks for 24 weeks, then every 12 weeks or as needed. Assessments of computed tomography scans for ILD will be conducted by a central expert review board.

Wenjuan, S., et al. (2021). "The effect of tea on polycystic ovary syndrome (PCOS): a protocol for a systematic review and meta-analysis."
	
Wenqi, L., et al. (2022). "Comparative effectiveness of non-surgical interventions for urinary incontinence in elderly women: a systematic review and network meta-analysis."
	
Wenrui, H., et al. (2022). "Acupuncture and Chinese herbal medicines for the treatment of tubal obstructive infertility: A systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Wens Francis, S. P. L., et al. (2023). "Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Patient Characteristics, Treatment, and Outcome-A Systematic Review." Cancers 15(15).
	Background: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since the discovery of mutations in the SMARCA4 gene in 2014, SCCOHT has become the subject of extensive investigation. However, international uniform treatment guidelines for SCCOHT are lacking and the outcome remains poor. The aim of this systematic review is to generate an overview of all reported patients with SCCOHT from 1990 onwards, describing the clinical presentation, genetic characteristics, treatment, and outcome.; Methods: A systematic search was performed in the databases Embase, Medline, Web of Science, and Cochrane for studies that focus on SCCOHT. Patient characteristics and treatment data were extracted from the included studies. Survival was estimated using Kaplan-Meier's methodology. To assess the difference between survival, the log-rank test was used. To quantify the effect of the FIGO stage, the Cox proportional hazard regression model was estimated. The chi-squared test was used to study the association between the FIGO stage and the surgical procedures.; Results: Sixty-seven studies describing a total of 306 patients were included. The median patient age was 25 years (range 1-60 years). The patients mostly presented with non-specific symptoms such as abdominal pain and sometimes showed hypercalcemia and elevated CA-125. A great diversity in the diagnostic work-up and therapeutic approaches was reported. The chemotherapy regimens were very diverse, all containing a platinum-based (cisplatin or carboplatin) backbone. Survival was strongly associated with the FIGO stage at diagnosis.; Conclusions: SCCOHT is a rare and aggressive ovarian cancer, with a poor prognosis, and information on adequate treatment for this cancer is lacking. The testing of mutations in SMARCA4 is crucial for an accurate diagnosis and may lead to new treatment options. Harmonization and international collaboration to obtain high-quality data on diagnostic investigations, treatment, and outcome are warranted to be able to develop international treatment guidelines to improve the survival chances of young women with SCCOHT.

Wentao, L., et al. (2021). "In-vitro fertilization versus ovarian stimulation - intrauterine insemination for the management of unexplained infertility: A Collaborative Individual Participant Data Meta-analysis."
	
Wentao, Y., et al. (2023). "Meta-analysis of dydrogesterone for the prevention of postoperative recurrence of endometrial polyps."
	
Wenwen, Y., et al. (2021). "The impact of bariatric surgery on obese polycystic ovary syndrome: a meta-analysis and systematic review."
	
Wessel, J. A., et al. (2022). "Ovarian stimulation strategies for intrauterine insemination in couples with unexplained infertility: a systematic review and individual participant data meta-analysis." Human Reproduction Update 28(5): 733-746.
	Background: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. Individual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of individual studies by obtaining the IPD, and allows analyses on treatment-covariate interactions to identify couples who benefit most from a particular treatment.; Objective and Rationale: We performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment-covariate interactions for important baseline characteristics in couples undergoing IUI.; Search Methods: We searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA.; Outcomes: Seven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12-1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33-3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05-1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94-1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45-1.96; RR 0.81, 95% CI 0.32-2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when compared to CC (6 RCTs, 2058 women, HR 1.37, 95% CI 1.15-1.63, I2 = 22%). No strong evidence on the treatment-covariate (female age, BMI or primary versus secondary infertility) interactions was found.; Wider Implications: In couples with unexplained infertility undergoing IUI-OS, gonadotrophins increased the chance of a live birth and reduced the time to conception compared to CC, at the cost of a higher multiple pregnancy rate, when not differentiating strategies on cancellation criteria or the starting dose. The treatment effects did not seem to differ in women of different age, BMI or primary versus secondary infertility. In a modern practice where a lower starting dose and stricter cancellation criteria are in place, effectiveness and safety of different agents seem both acceptable, and therefore intervention availability, cost and patients' preferences should factor in the clinical decision-making. As the evidence for comparisons to letrozole is based on one RCT providing IPD, further RCTs comparing letrozole and other interventions for unexplai ed infertility are needed. (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Wessel, J. A., et al. (2022). "Expectant management versus IUI in unexplained subfertility and a poor pregnancy prognosis (EXIUI study): a randomized controlled trial." Human Reproduction 37(12): 2808-2816.
	STUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births? SUMMARY ANSWER: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births. WHAT IS KNOWN ALREADY: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain. STUDY DESIGN, SIZE, DURATION: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM. LIMITATIONS, REASONS FOR CAUTION: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants. WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS. STUDY FUNDING/COMPETING INTEREST(S): The trial was supported by a grant of the SEENEZ healthcare initiative. The subsidizing parties were The Dutch Organisation for Health Research and Development (ZonMW 837004023, www.zonmw.nl) and the umbrella organization of 10 health insurers in The Netherlands. E.R.G. receives personal fees from Titus Health care outside the submitted work. M.G. declares unrestricted research and educational grants from Guerbet, Merck and Ferring not related to the presented work, paid to their institution VU medical centre. A.B.H. reports receiving travel and speakers fees from Nordic Pharma and Merck and he is member of the Nordic Pharma ANGEL group and of the Safety Monitoring Board of Womed. C.B.L. reports speakers fee from Inmed and Yingming, and his department receives research grants from Ferring, Merck and Guerbet paid to VU medical centre. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy for ObsEva and Merck. M.v.W. received a grant from the Netherlands Organisation for Health Research and Development ZonMW (80-8520098-91072). F.M received two grants from the Netherlands Organisation for Health Research and Development ZonMW (NTR 5599 and NTR 6590). The other authors report no competing interest. TRIAL REGISTRATION NUMBER: Dutch Trial register NL5455 (NTR5599) TRIAL REGISTRATION DATE: 18 December 2015 DATE OF FIRST PATIENT'S ENROLMENT: 26 January 2017.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

Westerhoff, B., et al. (2019). "About:blank? Online Interventions for Postpartum Depression." Verhaltenstherapie 29(4): 254-264.
	
Westerman, R. and A. K. Kuhnt (2022). "Metabolic risk factors and fertility disorders: A narrative review of the female perspective." Reproductive biomedicine & society online 14: 66-74.
	Metabolic risk factors such as obesity are considered major obstacles to female fertility. Chronic infertility imposes psychological and social burdens on women because infertility violates societal gender roles. Although the prevalence of obesity among women is expected to increase in the future, the relevance of metabolic status for fertility is still underestimated. However, the assessment of metabolic risk factors is highly relevant for understanding fertility disorders and improving infertility treatment. This narrative review discusses the associations of metabolic risk factors (e.g. obesity, female athlete triad, oxidative stress) with significant infertility. An electronic search was conducted for studies published between 2006 and 2020 in Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, PubMed, Scopus, Google Scholar and related databases. In total, this search identified 19,309 results for polycystic ovary syndrome, 28,969 results for endometriosis, and only 1611 results for idiopathic and/or unknown infertility. For the present narrative review, 50 relevant studies were included: 19 studies were on obesity, 24 studies investigated the female athlete triad, and seven studies addressed other risk factors, including reactive oxygen species. This narrative review confirms the direct impact of obesity on female infertility, while the effect of other risk factors needs to be confirmed by large-scale population studies.

Westermann, A., et al. (2024). "PAZEC: a Dutch Gynaecological Oncology Group open-label, multicenter, phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer." International Journal of Gynecological Cancer: ijgc-2023.
	Objective There is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer. Methods In this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, documented progressive disease, and a WHO performance status of <=2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity, or patient refusal. The primary endpoint was progression-free survival at 3 months, with secondary outcomes of overall response rate, progression-free survival, overall survival, and toxicity. The study was powered to demonstrate 50% progression-free survival at 3 months with alpha=0.05 and beta=80%. Results Between January 2011 and February 2016, 60 eligible patients were included (intention-to-treat population). Median age was 68 (range, 53-85) years. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%), and hormonal therapy (43%). Three-month progression-free survival was 63.3% in the intention-to-treat population, with median progression-free survival and overall survival of 3.4 and 7.5 months, respectively. Overall response rate was 8.3%, and median follow-up 7.6 months. The most common grade 3 or higher adverse events were gastrointestinal toxicity in 21% of participants, including two patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula, and one fatal enterovaginal fistula. Extensive peritoneal disease existed in 80% of the patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established. Conclusions Pazopanib met its primary endpoint of 3 months' progression-free survival in advanced endometrial cancer (63.3%), but response rates were modest. There may be a correlation for rare but severe gastrointestinal toxicity with previous treatments and/or disease site that has yet to be elucidated.Copyright © IGCS and ESGO 2024.

Westin, S. N., et al. (2024). "Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial." Journal of Clinical Oncology 42(3): 283-299.
	PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab 1 olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab 1 olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-totreat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P =. 003) and durvalumab 1 olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P <. 0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR[durvalumab v control], 0.42 [95%CI, 0.22 to 0.80];HR[durvalumab1 olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95%CI, 0.60 to 0.97]; HR [durvalumab 1 olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95%CI, 0.48 to 0.83]; HR [durvalumab 1 olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control:HR, 0.77 [95%CI, 0.56 to 1.07]; P 5.120; durvalumab1olaparib v control: HR, 0.59 [95%CI, 0.42 to 0.83]; P =. 003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.Copyright © 2023 by American Society of Clinical Oncology.

Wetherell, S. (2024). "A controlled study of brief online eye movement desensitization and reprocessing (EMDR) therapy to treat symptoms of childbirth trauma experience." Dissertation Abstracts International: Section B: The Sciences and Engineering 85(1-B): No-Specified.
	Childbirth traumatic experiences are an overlooked area of maternal psychological suffering that can lead to posttraumatic stress disorder, perinatal mood and anxiety disorder, and adverse infant outcomes. A literature review demonstrated that there had been little research into the use of brief trauma interventions for this population in the postpartum period and a lack of evidence in delivering such interventions online. This study examined the effectiveness of eye movement desensitization and reprocessing (EMDR) as a treatment for trauma symptomatology related to adverse childbirth experiences, compared to a control group intervention. Twenty-six mothers with significant trauma symptoms related to their childbirth experience were randomly assigned to a treatment or control group. Participants in the intervention group received three 90-minute online sessions following the standard EMDR protocol. Participants in the control group received three 90-minute online sessions of a stabilizing procedure to enhance access to positive memories, similar to positive affect training. Each subject took the impact of events scale revised (IES-R) and the birth trauma city scale (BiTS) before and after the intervention and at the six-month follow-up.Pre- to post-treatment Wilcoxon signed ranks tests for the EMDR group showed a significant reduction in trauma scores (p(1-tail) < 0.0002) with a large effect size (d = 0.8) based on the IES-R and a small to medium effect size (d = 0.4) based on the BiTS. Between-group comparison using a Mann-Whitney U test showed a significant statistical difference in the direction of functionality, with EMDR showing superior treatment gains based on the IES-R (z = -0.2.184, p = .028). Still, the difference between groups didn't reach statistical significance based on the BiTS questionnaire (z = -0.951, p = .355). Follow-up with participants at six months post-treatment showed sustained gains.The results of this study support the hypothesis that EMDR is an effective treatment for women suffering from trauma symptomatology related to an adverse childbirth experience. Additionally, this investigation's brief and online delivery format can potentially reduce barriers to accessing mental health treatment postpartum for the millions of women affected by this issue every year. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

White, A. B., et al. (2021). "Female Sexual Function following Sling Surgery: A Prospective Parallel Cohort, Multi-Center Study of the Solyx™ Single Incision Sling System versus the Obtryx™ II Sling System." The Journal of Urology 206(3): 696-705.
	PURPOSE: Limited data exist regarding sexual function after single incision sling (SIS) surgery. We compared sexual function 36 months postoperatively between patients undergoing SIS and transobturator sling (TMUS) for treatment of stress urinary incontinence. MATERIALS AND METHODS: Assessment of sexual function was a planned secondary objective of this prospective, multi-center study that enrolled women to Solyx SIS or Obtryx II TMUS. The primary study aim was to compare efficacy and safety using non-inferiority design at 36 months. Patient-reported outcomes of sexual function were assessed at baseline and 6, 12, 18, 24 and 36 months using Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Changes in sexual function were analyzed within and between groups. Outcomes for patients requiring surgical retreatment were determined. RESULTS: Baseline characteristics were balanced using propensity score stratification (N=141 SIS, N=140 TMUS). Groups were similar in age, body mass index and concomitant surgery performed. Average length of followup was 30 months. Baseline sexual activity was similar (123/141 SIS, 114/140 TMUS, p=0.18). Severity of urinary incontinence did not correlate with baseline sexual activity. Mean PISQ-12 scores increased significantly from baseline to 36 months for both groups, indicating better sexual function at each visit. There were no significant differences in PISQ-12 scores between groups except at 36 months, where the difference was small (-2.5, 95% CI [-4.7, 0.2]). Among patients undergoing surgical retreatment (9/281, 3%), improvement in sexual function was maintained. De novo dyspareunia was rare following both treatments (SIS 1/141, TMUS 0/140, p=1.00). CONCLUSIONS: Patients have significant improvement in sexual function after SIS and TMUS. De novo sexual pain is low after sling surgery.

Whitney, G., et al. (2021). "Efficacy of Individualized Starting Dose (ISD) and Fixed Starting Dose (FSD) of Niraparib per Investigator Assessment (IA) in Newly Diagnosed Advanced Ovarian Cancer (OC) Patients." Journal of Obstetrics and Gynaecology Research 47(8): 2803‐2804.
	Niraparib is a PARPi approved for maintenance treatment of patients with newly diagnosed/recurrent OC that responded to platinum‐based chemotherapy and treatment in heavily pretreated recurrent OC. Here we report efficacy in patients receiving FSD and ISD in the PRIMA/ENGOT‐OV26 / GOG‐3012 trial (NCT02655016). [Methods] This double‐blind, placebo‐controlled, phase 3 study randomized 733 patients to receive niraparib or placebo until disease progression or toxicity. A protocol amendment introduced ISD : 200 mg in patients with bodyweight <7 7 kg or platelets <150,000/μL, or 300 mg in all others. Primary endpoint was PFS by blinded independent central review (BICR). IA PFS was a sensitivity analysis. Primary analysis data cut follow‐up was 11.2 months and 17.1 months in ISD and FSD subgroups, respectively. Ad hoc analysis of IA PFS was performed using updated data cut with additional 6 months follow‐up. [Results] The hazard ratio for IA PFS tHR 0.63 [95%CI 0.51‐0.76]) from the original data cut was similartoIAPF S (HR 0.64 [95%CI 0.53‐0.77]) from the updated data cut. Based on the IA PFS from the original data cut, niraparib efficacy was comparable between FSD (n=487 ; HR 0.60 [95%CI 0.47‐0.77]) and ISD (n=246 ; HR 0.68 [95%CI 0.48‐0.96]). Similarly, with IA PFS from the updated data cut, niraparib efficacy was comparable between FSD (HR0.62 [95%CI 0.49‐0.78]) and ISD (HR0.68 [95%CI 0.49‐0.94]). Dose interruptions, modifications, and hematologic toxicity were lower with ISD. [Conclusion] ISD by baseline bodyweight and platelets demonstrated comparable efficacy while improving the safety profile of niraparib. New data will be presented in the presentation.

Whitney, R., et al. (2021). "Female chronic pelvic pain and sexual trauma: a systematic review and meta-analysis."
	
Widdison, R., et al. (2022). "Effectiveness of mobile apps to improve urinary incontinence: a systematic review of randomised controlled trials." BMC nursing 21(1): 32.
	INTRODUCTION: Pelvic floor exercises are effective in the treatment of urinary incontinence (UI) and are routinely prescribed, along with bladder training, by primary healthcare providers as first line conservative management. Mobile phone applications are increasingly popular within the healthcare setting and can provide opportunities for patients to complete treatments at home. To date, there has not been a systematic review examining outcomes from randomised controlled trials on the effectiveness of mobile applications to improve UI. METHODS: A systematic review of randomized controlled trials evaluating the effectiveness of mobile applications to improve UI was carried out according to the PRISMA reporting guidelines. The online databases MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Scopus, The Cochrane Library, Joanna Briggs Institute (JBI), Google Scholar were searched for papers published between 2007 to 2020. Keywords and MeSH terms were used to identify relevant English language studies. The quality and risk of bias within included studies was assessed by two independent reviewers, RCT JBI critical appraisal tool. Due to heterogeneity in the outcome of studies, a meta-analysis of the data could not be conducted. FINDINGS: Four studies reported an improvement in the outcome assessed post-intervention, suggesting that using mobile phone applications for pelvic floor muscle training (PFMT) was an acceptable and valid intervention to improve UI. CONCLUSION: Mobile applications for PFMT indicated that increase adherence to treatment and decrease UI. The integration of this treatment modality into current practice is recommended. Mobile phone applications for PFMT show promise in the conservative management of UI. Further research is required to support the use of this technology in the conservative management of UI.

Widia, F., et al. (2023). "The efficacy of antibiotic and alpha-blocker combination therapy versus antibiotic monotherapy in chronic prostatitis/chronic pelvic pain syndrome: A systematic review." Lower urinary tract symptoms 15(4): 107-115.
	Objectives: This study attempted to explore the efficacy of a combination of alpha-blockers and antibiotics compared with antibiotic monotherapy in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).; Methods: We searched PubMed/MEDLINE, Cochrane/CENTRAL, EBSCOHost/CINAHL, ProQuest, and Scopus on January 2020. Randomized controlled trials comparing antibiotic monotherapy with combination therapy of antibiotics and alpha-blockers in CP/CPPS patients lasting at least 4 weeks were included. The study eligibility assessment, data extraction, and study quality assessment were carried out by each author independently and in duplication.; Results: A total of six low- to high-quality studies with 396 patients were included in the study. Two reviews reported lower National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total scores in the monotherapy arm at Week 6. Only one study reported otherwise. On Day 90, the NIH-CPSI score was found to be lower in the combination group. In the pain, urinary, and quality-of-life domain, most studies agree that combination therapy is not superior to monotherapy. However, on Day 90, all domains were found to be lower in the combination therapy. Responder rates were found to vary between studies. Only four out of six studies reported a response rate. Responder rates were lower in the combination group at 6 weeks of observation. On Day 90, responder rates were found to be better in the combination group.; Conclusions: The combination therapy of antibiotics and alpha-blockers is not substantially better than antibiotic monotherapy in the first 6 weeks of treatment for CP/CPPS patients. This might not be applicable to a longer duration of treatment. (© 2023 John Wiley & Sons Australia, Ltd.)

Wieland, U. and M. Hampl (2023). "HPV vaccination: new data and indication for secondary prevention." Gynakologie 56(12): 889-896.
	Human papillomaviruses (HPV) cause numerous benign and malignant lesions/tumors of skin and mucosa, including genital warts, recurrent laryngeal papillomatosis (RLP), precancerous lesions, and cancers of the cervix, vulva, vagina, anus, and penis as well as oropharyngeal cancer. Worldwide, 4-5% of all cancers are caused by HPV. Most HPV-associated diseases are vaccine preventable, whereby young age at vaccination or HPV naivety are important. In countries with high HPV vaccination rates among children and adolescents, we are already seeing large reductions in genital warts, high-grade cervical dysplasia (CIN2+), and cervical cancer. Off-label use of HPV vaccination around conization or for present HPV-induced lesions is discussed controversially. Three meta-analyses of HPV vaccination for post-conization prophylaxis show varying degrees of risk reduction for the development of CIN2+ after conization, with only two controlled trials available to date. For RLP, meta-analyses also conclude that off-label HPV vaccination may be useful as adjuvant therapy, but further studies are needed. Elimination of cervical cancer is a World Health Organization (WHO) goal. This requires HPV vaccination rates of 90% in girls up to 15 years of age. Efforts to increase vaccination rates are needed in Germany, where the HPV vaccination rate among 15-year-old girls is only 54%.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Wierzbicka, A., et al. (2021). "Interventions Preventing Vaginitis, Vaginal Atrophy after Brachytherapy or Radiotherapy Due to Malignant Tumors of the Female Reproductive Organs-A Systematic Review." International Journal of Environmental Research and Public Health 18(8).
	Background: Radiotherapy, as a method of treatment of cervical and uterine cancers, may induce severe late-onset vaginal side effects. Unfortunately, little evidence on the management of adverse effects has been presented. This study aimed to evaluate the available interventions which reduce symptoms of vaginitis and vaginal atrophy by improving dyspareunia, mucosal inflammation, vaginal pH and vaginal dryness in women who have undergone brachytherapy or radiotherapy due to uterine or cervical malignancies.; Materials and Methods: A comprehensive literature search was performed following PRISMA guidelines. The systematic search was conducted using electronic databases, namely Scopus, Web of Science and PubMed, between October and November 2020 to identify randomized controlled trials (RCT) and, prospective randomized studies (PRS).; Results: The analyzed population consists of 376 patients with uterine or cervical cancer, treated with hyaluronic acid, vitamin A, vitamin E, alpha-tocopherol acetate and dienestrol. Intervention with HA along with vitamin A and vitamin E revealed advantage in endpoints such as reduced dyspareunia, vaginal mucosal inflammation, vaginal dryness, bleeding, fibrosis and cellular atypia. Administration of alpha-tocopherol acetate reduced vaginal mucosal inflammation and improved vaginal acanthosis, whereas dienestrol resulted in reduced dyspareunia, vaginal caliber and bleeding.; Conclusions: Vaginal suppositories were found to be clinically effective at the management of late-onset vulvovaginal side effects after radiotherapy.

Wiesenfeld, H. C., et al. (2021). "A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 72(7): 1181-1189.
	BACKGROUND: Anaerobic organisms are important pathogens in acute pelvic inflammatory disease (PID). The currently recommended PID regimen of a single dose of ceftriaxone and doxycycline for 14 days has limited anaerobic activity. The need for broader anaerobic coverage is unknown and concerns have been raised about metronidazole tolerability. METHODS: We conducted a randomized, double-blind, placebo-controlled trial comparing ceftriaxone 250 mg intramuscular single dose and doxycycline for 14 days, with or without 14 days of metronidazole in women with acute PID. The primary outcome was clinical improvement at 3 days following enrollment. Additional outcomes at 30 days following treatment were the presence of anaerobic organisms in the endometrium, clinical cure (absence of fever and reduction in tenderness), adherence, and tolerability. RESULTS: We enrolled 233 women (116 to metronidazole and 117 to placebo). Clinical improvement at 3 days was similar between the 2 groups. At 30 days following treatment, anaerobic organisms were less frequently recovered from the endometrium in women treated with metronidazole than placebo (8% vs 21%, P < .05) and cervical Mycoplasma genitalium was reduced (4% vs 14%, P < .05). Pelvic tenderness was also less common among women receiving metronidazole (9% vs 20%, P < .05). Adverse events and adherence were similar in each treatment group. CONCLUSIONS: In women treated for acute PID, the addition of metronidazole to ceftriaxone and doxycycline was well tolerated and resulted in reduced endometrial anaerobes, decreased M. genitalium, and reduced pelvic tenderness compared to ceftriaxone and doxycycline. Metronidazole should be routinely added to ceftriaxone and doxycycline for the treatment of women with acute PID. CLINICAL TRIALS REGISTRATION: NCT01160640.

Wijaya, S. T., et al. (2022). "Impact of homologous recombination deficiency (HRD) on outcomes with intraperitoneal (IP) and intravenous (IV) chemotherapy in ovarian cancer: Analyses from the translational iPocc study (TriPocc)." Annals of Oncology 33(Supplement 7): S811.
	Background: The iPocc randomised multicentre international study reported improved progression-free survival (PFS) but not overall survival (OS) with IP carboplatin and IV paclitaxel vs IV chemotherapy (chemo) in patients (pts) with epithelial ovarian, fallopian tube or primary peritoneal cancer. Previous studies suggested that pts with BRCA-deficient tumours may benefit from IP chemo. We conducted a non-prespecified analysis of the prognostic and predictive value of HRD in tissue samples retrospectively obtained from iPocc trial pts. Method(s): 166 pts from participating centres in Singapore and Japan had adequate tissue for next-generation sequencing with ACT Genomics ACTOnco+. HRD was defined by high loss of heterozygosity at a threshold of >=0.35 (LOH high) or presence of a pathogenic BRCA mutation (BRCAmt). Median PFS and OS were estimated using Kaplan-Meier method. Fisher's exact and Student's t-test were used to compare group characteristics. Result(s): Both IP and IV arms had similar frequencies of BRCAmt, homologous recombination repair pathway mutations (HRRmt) and LOH high. All BRCAmt tumours were LOH high. There were no differences in PFS or OS in IP vs IV arms in this cohort. Outcome data based on HRD subgroups are summarised in the table. In the overall group, LOH high was associated with improved OS (HR 0.43, p=.001) but not PFS (HR 1.04, p=.87). BRCAmt pts showed a trend towards improved OS (HR 0.68, p=.24) and PFS (HR 0.73, p=.32). HRRmt status did not significantly affect OS (HR 0.95, p=.84) or PFS (HR 1.21, p=.30). [Formula presented] Conclusion(s): In this small subgroup analysis of iPocc pts, BRCAmt pts demonstrated a trend towards improved PFS and OS with IP compared with IV chemo. BRCAmt and LOH high, but not HRRmt, correlated with improved outcomes in the overall group. Larger prospective studies with integrated molecular analyses are needed to better define the impact of HRD in IP vs IV chemo. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: A. Yabuno: Other, Personal and Institutional, Other, Honoraria: Takeda, AstraZeneca, Eisai. All other authors have declared no conflicts of interest.Copyright © 2022 European Society for Medical Oncology

Wikana, J. (2019). "Utilizing bioidentical hormone as efficacious and safe hormone." Journal of Global Pharma Technology 11(6 Supplement): 130-144.
	Background: The relative safety and efficacy of bioidentical hormone compared with synthetic version of hormone replacement therapy (HRT) is still the subject of debate. Some data suggest that bioidentical hormones have opposite physiological effects to synthetic hormones, which associated with lower risk of breast cancer and cardiovascular events. Nevertheless, there is still little evidence to support claims that bioidentical hormones are safer and more effective. Method(s): Published papers were identified from PLOS, PubMed/MEDLINE, ProQuest, ScienceDirect, Google Scholar, and Elsevier (SCOPUS) databases, written in English, and fully accessible by reviewers, for studies enrolled postmenopausal women using bioidentical hormones vs. synthetic hormones as HRT. Result(s): A hundred and eighteen of 341 citations were reviewed. The results of this study found the disparities between bioidentical and synthetic hormones with respect to safety and efficacy. Bioidentical hormones have demonstrated effectiveness in addressing menopausal symptoms. Clinical data has indicated that bioidentical hormone, especially progesterone is associated with a diminished risk for breast cancer and cardiovascular disease, compared with commonly used synthetic versions. Conclusion(s): The use of bioidentical hormone therapy is well tolerated, provides symptom relief and can address the safer and more efficacious forms of HRT with respect to the lower risk for breast cancer and cardiovascular disease. Thus, bioidentical hormones remain the preferred method of HRT.Copyright © 2009-2019, JGPT. All Rights Reserved.

Wikström, T., et al. (2022). "Cost-effectiveness of cervical length screening and progesterone treatment to prevent spontaneous preterm delivery in Sweden." Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 59(6): 778-792.
	Objective: To estimate the cost-effectiveness of strategies to prevent spontaneous preterm delivery (PTD) in asymptomatic singleton pregnancies, using prevalence and healthcare cost data from the Swedish healthcare context.; Methods: We designed a decision analytic model based on the Swedish CERVIX study to estimate the cost-effectiveness of strategies to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy. The model was constructed as a combined decision-tree model and Markov model with a time horizon of 100 years. Four preventive strategies, namely 'Universal screening', 'High-risk-based screening' (i.e. screening of high-risk women only), 'Low-risk-based screening' (i.e. treatment of high-risk population and screening of remaining women) and 'Nullipara screening' (i.e. treatment of high-risk population and screening of nulliparous women only), included second-trimester cervical length (CL) screening by transvaginal ultrasound followed by vaginal progesterone treatment in the case of a short cervix. A fifth preventive strategy involved vaginal progesterone treatment of women with previous spontaneous PTD or late miscarriage but no CL screening ('No screening, treat high-risk group'). For comparison, we used a sixth strategy implying no specific intervention to prevent spontaneous PTD, reflecting the current situation in Sweden ('No screening'). Probabilities for a short cervix (CL ≤ 25 mm; base-case) and for spontaneous PTD at < 33 + 0 weeks and at 33 + 0 to 36 + 6 weeks were derived from the CERVIX study, and probabilities for stillbirth, neonatal mortality and long-term morbidity (cerebral palsy) from Swedish health data registers. Costs were based on Swedish data, except costs for cerebral palsy, which were based on Danish data. We assumed that vaginal progesterone reduces spontaneous PTD before 33 weeks by 30% and spontaneous PTD at 33-36 weeks by 10% (based on the literature). All analyses were from a societal perspective. We expressed the effectiveness of each strategy as gained quality-adjusted life years (QALYs) and presented cost-effectiveness as average (ACER; average cost per gained QALY compared with 'No screening') and incremental (ICER; difference in costs divided by the difference in QALYs for each of two strategies being compared) cost-effectiveness ratios. We performed deterministic and probabilistic sensitivity analysis. The results of the latter are shown as cost-effectiveness acceptability curves. Willingness-to-pay was set at a maximum of 500 000 Swedish krona (56 000 US dollars (USD)), as suggested by the Swedish National Board of Health and Welfare.; Results: All interventions had better health outcomes than did 'No screening', with fewer screening-year deaths and more lifetime QALYs. The best strategy in terms of improved health outcomes was 'Low-risk-based screening', irrespective of whether screening was performed at 18 + 0 to 20 + 6 weeks (Cx1) or at 21 + 0 to 23 + 6 weeks (Cx2). 'Low-risk-based screening' at Cx1 was cost-effective, while 'Low-risk-based screening' at Cx2 entailed high costs compared with other alternatives. The ACERs were 2200 USD for 'Low-risk-based screening' at Cx1 and 36 800 USD for 'Low-risk-based screening' at Cx2. Cost-effectiveness was particularly sensitive to progesterone effectiveness and to productivity loss due to sick leave during pregnancy. The probability that 'Low-risk-based screening' at Cx1 is cost-effective compared with 'No screening' was 71%.; Conclusion: Interventions to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy, including CL screening with progesterone treatment of cases with a short cervix, may be cost-effective in Sweden. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in O stetrics and Gynecology.)

Wilczyńska, D., et al. (2023). "Stress is not so bad-cortisol level and psychological functioning after 8-week HIIT program during pregnancy: a randomized controlled trial." Frontiers in Public Health 11: 1307998.
	BACKGROUND: Amid extensive pregnancy exercise research, the impact of High Intensity Interval Training (HIIT) on pregnant women's mental health is underexplored. Despite exercise benefits, it can trigger stress responses like elevated cortisol. This study fills the gap by investigating correlations between hair cortisol levels, mental health, and HIIT effects in pregnant women. METHODS: We conducted a randomized control trial among 38 Caucasian women in uncomplicated, singleton pregnancy (age 31.11 ± 4.03 years, 21.82 ± 4.30 week of gestation; mean ± SD). The experimental group comprised 22 women engaged in an 8-week high-intensity interval training program (HIIT). The comparative group consisted of 16 pregnant women undergoing an 8-week educational program (EDU). Before and after the interventions, all women were evaluated using the following tools: Hair cortisol level measurements, Beck Depression Inventory - II for depressive symptoms assessment, Childbirth Attitudes Questionnaire for childbirth fear measurement, 12-item Short Form Health Survey to gage health-related quality of life, International Physical Activity Questionnaire for physical activity level estimation, and a Progressive maximal exercise test to evaluate maternal exercise capacity. RESULTS: The key finding of our study reveals that women engaged in the HIIT intervention exhibited a distinct cortisol production pattern in contrast to the EDU group practicing standard moderate intensity physical activity. In the HIIT group, there was an increase in hair cortisol levels, while the EDU group showed a notable decrease. Remarkably, HIIT stimulated cortisol production without adversely impacting fear of childbirth and psychophysical condition during pregnancy. In fact, only the HIIT group showed a significant enhancement in mental health. CONCLUSION: No links were discovered between hair cortisol levels and the severity of depressive symptoms, psychophysical well-being, or fear of childbirth. Hence, based on our research, employing cortisol levels during pregnancy as an indicator of negative stress or depression risk appears unwarranted.

Wilky, B., et al. (2022). "BOTENSILIMAB, A NOVEL INNATE/ADAPTIVE IMMUNE ACTIVATOR, PLUS OR MINUS BALSTILIMAB (ANTI-PD-1) IN "COLD" AND I-O REFRACTORY METASTATIC SOLID TUMORS." Journal for Immunotherapy of Cancer 10(Supplement 2): A809.
	Background Botensilimab (BOT) promotes optimized T cell priming, activation and memory formation by strengthening antigen presenting cell/T cell co-engagement. As an Fcenhanced next-generation anti-CTLA-4 antibody, BOT also promotes intratumoral Treg depletion and reduces complement fixation. We present results from patients with metastatic solid tumors treated with BOT+/-balstilimab (BAL; anti-PD-1) in an expanded phase IA/B study; NCT03860272. Methods Patients received either BOT monotherapy at 0.1-3 mg/kg every 3 weeks (Q3W), BOT monotherapy 1 or 2mg/kg every 6 weeks (Q6W), BOT 0.1-2mg/kg Q6W+BAL 3 mg/kg every 2 weeks, or a fixed-dose of BOT 150mg Q6W+BAL 450mg Q3W. Unconfirmed responses are included. Of the 44 BOT monotherapy patients, 13 crossed over to combination. Results 142 patients (98 combination, 44 monotherapy [13 crossover]) were evaluable for efficacy/safety (treated as of April 7, 2022 with >=1 Q6W tumor-imaging assessment). Patients had immunologically cold and/or immunotherapy resistant tumors and were heavily pretreated: 61% received >=3 prior lines of therapy including 34% prior immunotherapy. Median follow-up was 6.1 months. Disease-specific combination therapy cohorts are being expanded with BOT at 1 or 2mg/kg or 150mg+BAL (including 4 crossover patients): (1) microsatellite stable (MSS) colorectal cancer (n=44, ORR 25%), (2) platinum resistant ovarian cancer (n=18, ORR 28%), (3) sarcoma (n=12, ORR 42%, and (4) PD-(L)1 relapsed/refractory non-small cell lung cancer (n=3, ORR 67%). The ORR was 22% (22/98; 3 CR/19 PR) with median duration of response [DOR] not reached (range,1.4+ to 19.5 + months) in all combination patients (BAL+BOT 0.1-2 mg/ kg or 150 mg); 13/22 responses are ongoing. In addition, 15% (2/13) monotherapy patients achieved PR after crossing over to combination therapy. The ORR was 11% (5/44; 1 CR/4 PR) in all monotherapy patients (BOT 0.1-3 mg/kg). Responses were independent of PD-L1 expression and tumor mutation burden. Further evaluation of biomarkers is ongoing including paired biopsies (before/during treatment). Grade 1/2, 3 or 4 treatment-related adverse events (TRAE) occurred in 88%, 29%, 2% respectively. Diarrhea/colitis (19%) was the only grade 3/4 TRAE occurring in >=5% of patients. There were no cases of hypophysitis or myocarditis. Pneumonitis occurred in 4 patients (3%). Two patients had grade 5 TRAEs (enterocolitis, colonic perforation). Conclusions BOT+/-BAL demonstrates remarkable activity in heavily pretreated patients with solid tumors historically unresponsive to immunotherapy. The safety profile is consistent with the mechanism of action of BOT. Randomized studies in MSS CRC, pancreatic cancer, and melanoma are planned to open this year.

Willi, J. and U. Ehlert (2019). "Assessment of perimenopausal depression: A review." Journal of Affective Disorders 249: 216-222.
	BACKGROUND: Within the female life cycle, the perimenopause is considered as a critical period for the development of depression. Prevalence rates are particularly high during this phase. Perimenopausal depression is characterized by affective symptoms as well as menopause-specific somatic complaints. Currently, a variety of questionnaires are used to assess mood during the perimenopause. The aim of this review is to determine the instruments employed to assess perimenopausal depression. METHODS: We searched the databases PubMed, Cochrane Library and PsycINFO for human studies investigating perimenopausal depression, and subsequently screened for the assessment instruments used to measure mood and menopause. A total of 37 articles were included. RESULTS: Altogether, 14 different instruments were applied to assess mood during menopause. The CES-D was by far the most frequently used depression scale, appearing in 16 out of the 37 studies. The methods used to identify perimenopausal status and symptoms were inconsistent. LIMITATIONS: Due to lacking information about data and methodology, a selection bias is conceivable. Additionally, a publication bias is possible. Finally, there is inevitable subjectivity in the screening process of a systematic search. CONCLUSIONS: The assessment of depression in the menopausal transition is highly heterogeneous, reducing the overall comparability of study results. Furthermore, menopausal complaints are not sufficiently taken into account. Accordingly, the use of a menopause-specific depression scale is highly recommended in order to account for physical and mood-related symptoms in the menopausal transition.

Willi, J., et al. (2020). "Symptoms assessed in studies on perimenopausal depression: A narrative review." Sex. Reprod. Healthc. 26: 100559.
	The menopausal transition constitutes a phase of major biopsychosocial changes associated with an elevated risk for the development of depression. Perimenopausal depression is highly prevalent and usually characterized by core symptoms of a major depressive disorder combined with menopausal complaints such as vasomotor symptoms or other physical complaints. However, a distinct definition of the condition is lacking. The aim of this review is to portray the symptoms assessed in studies on perimenopausal depression in order to provide relevant information on the current understanding of this condition. A literature search was conducted using the databases PubMed, Cochrane Library, and PsycINFO. A total of 37 studies were included. Various assessment tools have been used to measure symptoms related to perimenopausal depression. Fifteen symptoms were identified. Depressed mood was assessed across all studies. Low energy or sleep disturbances, as acknowledged symptoms of a major depressive disorder, were surveyed in most studies. However, the assessment of menopausal complaints was rather heterogeneous. While vasomotor symptoms were often measured, other menopausal symptoms such as mood swings or pain were investigated less frequently. Sexual problems were only rarely assessed. Studies on perimenopausal depression regularly include the assessment of core symptoms of a major depressive disorder, but the assessment of menopausal complaints is inconsistent. While certain symptoms are commonly measured, others are not assessed. Such inconsistencies underline an ambiguous understanding of perimenopausal depression, which in turn affects the evaluation and treatment of the condition. Thus, the use of the existing guidelines on perimenopausal depression is recommended.

William, Q., et al. (2023). "Functional outcomes of bowel resection versus shaving or disc excision of colorectal endometriosis: a systematic review protocol."
	
Williams, A., et al. (2020). "The Effects of Vitamin D on Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Systematic Review." Hormone and metabolic research 52(7): 485-491.
	This systematic review aims to evaluate all epidemiological evidence in the literature linking the effect of vitamin D supplementation to metabolic and hormonal functions in women with polycystic ovary syndrome. The literature search was performed with two databases, namely Medline/PubMed and Web of Science, until 20 May 2019 for both observational and experimental studies concerning relationships between vitamin D and polycystic ovary syndrome. A total of ten studies with randomized, double-blinded, and placebo-controlled trial design from 2008 to 2019 were selected for this review. The inclusion criteria were women 18-45 years of age with polycystic ovary syndrome and comparing the metabolic or endocrine parameters between placebo and vitamin D supplementation groups. A total of ten studies were selected for this review. We found that vitamin D supplementation had a significant effect on insulin metabolism, total serum testosterone, hirsutism, C-reactive protein, and total antioxidant capacity in women with polycystic ovary syndrome. Evidence from available randomized controlled trials suggests that patients with polycystic ovary syndrome should take vitamin D supplementation for the beneficial effect of metabolic profiles. However, future research is needed regarding the beneficial effects in women who are non-obese with polycystic ovary syndrome, as well as more studies with larger sample sizes.Copyright © 2020 BioMed Central Ltd.. All rights reserved.

Williams, E., et al. (2022). Uterine artery embolization (UAE) compared with myomectomy for the management of uterine fibroids: a systematic review and meta-analysis.
	Background Uterine artery embolization (UAE) and myomectomy are uterus-sparing treatments for uterine fibroids. Each carries a different risk and efficacy profile. Despite this there is a lack of direct comparison between the two techniques making tre

Williams, M. E., et al. (2023). "Measuring post-traumatic stress after childbirth: a review and critical appraisal of instruments." Journal of Reproductive and Infant Psychology 41(5): 599-613.
	Background: Addressing psychological trauma after childbirth requires accurate measurement of its prevalence, risk factors, and outcomes using validated instruments that distinguish perceptions of traumatic birth, subclinical post-traumatic stress (PTS) symptoms, and symptoms meeting a diagnostic threshold. Objective(s): The purpose of this study was to review literature on psychological trauma following childbirth and appraise instruments that measure postpartum PTS. Method(s): In January 2020, the authors searched for and evaluated peer-reviewed studies that quantitatively measured PTS following hospital-based live births in the United States, United Kingdom, Canada, Australia, Norway, Sweden, and Switzerland; 37 articles were selected and evaluated. Result(s): Levels of post-traumatic stress disorder were most commonly measured, followed by PTS symptoms. Diagnostic instruments suggested lower PTS prevalence estimates than those screening for or assessing PTS symptoms. Community samples yielded lower prevalence estimates than samples recruited from the internet or settings specifically addressing mental health. Measurement sooner after birth yielded higher estimates. Conclusion(s): Study design, sample characteristics, instruments, and timing of measurements likely impact postpartum PTS prevalence estimates. Variation in these characteristics make it difficult to draw conclusions on the prevalence of postpartum PTS. Researchers should consider the appraisal of measurement tools presented here and use rigorous study methodology when studying traumatic birth experiences and evaluating interventions.Copyright ©, Society for Reproductive and Infant Psychology.

Williamson Casey, W., et al. (2023). "Outcomes from a 3-fraction high-dose-rate brachytherapy regimen for patients with cervical cancer." Brachytherapy 22(3): 317-324.
	Purpose: To estimate local control, survival, and toxicity associated with a 3-fraction (3F) image-guided brachytherapy (IGBT) regimen compared to longer fraction (LF) for cervical cancer.; Methods: 150 patients treated between 2015-2020 with 3F (24Gy in 3 fractions) or LF (28...30 Gy in 4-5 fractions) were reviewed. The primary outcome was 2-year local failure. We compared overall survival (OS), disease-free survival (DFS), hospitalizations, and toxicity.; Results: There were 32 patients in the 3F group and 118 in the LF group, with a median follow up of 22 months. The 3F had worse performance status (p = 0.01) but otherwise similar characteristics. The 2-year local failure rate was 3.6% (95% CI 0%, 10.6%) for 3F, and 7.5% (95% CI 2.4%, 12.6%) for LF. The univariable hazard ratio (HR) for local failure for 3F was 0.43 (0.05, 3.43; p = 0.43). Moreover, 2 of 32 (6.3%) 3F patients experienced Grade ...3 toxicity compared to 7 of 118 (5.9%) LF patients (p = 1.0), with no difference in hospitalization within 2 years (p = 0.66) and no treatment-related deaths.; Conclusions: Local control was excellent, with long term survival and toxicity similar between the groups. These findings support consideration of 3F. (Copyright © 2023. Published by Elsevier Inc.)

Williamson Casey, W., et al. (2022). "Positron Emission Tomography-Guided Bone Marrow-Sparing Radiation Therapy for Locoregionally Advanced Cervix Cancer: Final Results From the INTERTECC Phase II/III Trial." International Journal of Radiation Oncology, Biology, Physics 112(1): 169-178.
	Purpose: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.; Methods and Materials: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m 2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS.; Results: In total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ 2 P = .048) and in the combined cohort (13% vs 35%, χ 2 P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group.; Conclusions: PET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS. (Copyright © 2021 Elsevier Inc. All rights reserved.)

Willis-Gray, M. G., et al. (2021). "Is a Postvoid Residual Necessary? A Randomized Trial of Two Postoperative Voiding Protocols." Female Pelvic Medicine & Reconstructive Surgery 27(2): e256-e260.
	OBJECTIVES: This study aimed to compare a backfill-assisted voiding trial (VT) with and without a postvoid residual (PVR) after pelvic reconstructive surgery. METHODS: This was a nonblinded randomized controlled trial of women undergoing pelvic organ prolapse and/or stress incontinence surgery. Participants were randomized immediately after surgery to either a PVR VT or a PVR-free VT. Our primary outcome was the rate of VT failure at discharge. Secondary outcomes included days of catheterization, urinary tract infection (UTI), and prolonged voiding dysfunction. With a power of 80% and an α of 0.05, we needed 126 participants to detect a 25% difference in VT failure (60% in PVR VT vs 35% in PVR-free VT). RESULTS: Participants were enrolled from March 2017 to October 2017. Of the 150 participants, mean age was 59 years, and 33% underwent vaginal hysterectomy, 48% underwent anterior repair, and 75% underwent midurethral sling. Seventy-five (50%) were randomized to PVR VT and 75 (50%) to PVR-free VT, with no differences in baseline demographic or intraoperative characteristics between the 2 groups. Our primary outcome, VT failure, was not significantly different (53% PVR VT vs 53% PVR-free VT, P = 1.0). There were no significant differences in days of postoperative catheterization (1 [0, 4] in PVR VT vs 1 [0, 4] in PVR-free VT, P = 0.90), UTI (20% PVR VT vs 20% PVR-free VT, P = 1.0), or postoperative voiding dysfunction (4% PVR VT vs 5% PVR-free VT, P = 1.0). CONCLUSIONS: When performing a backfill-assisted VT, checking a PVR does not affect VT failure, postoperative duration of catheterization, UTI, or voiding dysfunction.

Wiltink, L. M., et al. (2020). "A systematic review of the impact of contemporary treatment modalities for cervical cancer on women's self-reported health-related quality of life." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 28(10): 4627-4644.
	Purpose: Given the high survival rate of cervical cancer patients, understanding women's health-related quality of life (HRQL) during and after treatment is of major clinical importance. We conducted a systematic review to synthesize all available evidence about the effects of each contemporary treatment modality for cervical cancer on all dimensions of women's HRQL, including symptoms, functioning, and global HRQL.; Methods: We searched four electronic databases from January 2000 to September 2019, cross-referenced and searched by author name for studies of patients treated for cervical cancer that reported patient-reported outcomes (PROs) before treatment and with at least one post-treatment measurement. Two independent reviewers applied inclusion and quality criteria and extracted findings. Studies were categorized by treatment to determine specific treatment effects on PROs. Results were narratively summarized.; Results: We found twenty-nine papers reporting 23 studies. After treatments with curative intent for early or locally advanced disease, lymphedema, diarrhea, menopausal symptoms, tight and shorter vagina, pain during intercourse, and sexual worries remained long-term problems; however, sexual activity improved over time. HRQL and psychological distress were impacted during treatment with also worsening of global HRQL but improved 3-6 months after treatment. In patients with metastatic or recurrent disease, pain improved during palliative treatment or remained stable, with no differences in global HRQL found over time.; Conclusion: Whereas most symptoms worsen during treatment and improve in the first 3 months after completing treatment, symptoms like lymphedema, menopausal symptoms, and sexual worries develop gradually and persist after curative treatment. These findings can be used to inform clinical practice and facilitate communication and shared decision-making. More research is needed in very early cervical cancer and the impact of fertility sparing therapy on PROs.

Winata, G. S., et al. (2023). "Adjuvant Therapy in Early-Stage Cervical Cancer Patients with Intermediate-Risk Factors, Comparing Between Chemotherapy and Radiotherapy: A Systematic Review and Meta-Analysis." Open Access Macedonian Journal of Medical Sciences 11(B): 639-647.
	BACKGROUND: Patients with early-stage cervical cancer (ESCC) after radical hysterectomy surgery usually need additional adjuvant treatment, but it depends on the presence or absence of certain risk factors. Factors, such as large tumor size, deep stromal invasion, and lymphovascular space involvement, are classified as intermediate risks. Therefore, postoperative adjuvant concurrent chemo-radiotherapy (CRT) or radiotherapy (RT) is recommended for ESCC with risk factors. However, it remains controversial whether CRT is superior to RT as an adjuvant regimen for postoperative with risk factors. METHOD(S): A systematic search was performed within PubMed, Cochrane, Science Direct, and Google Scholar databases to research the outcome between CRT and RT in ESCC. Three reviewers independently reviewed titles, abstracts, and full article text to identify studies meeting inclusion and exclusion criteria. If there are any discrepancies, it will be resolved by discussion. In this analysis, the Newcastle-Ottawa scale was used to assess the risk of bias of non-randomized studies. We used review manager 5.4 to calculate the result of 95% CI for the outcomes using odds ratio (OR), random effect model was also used if there is heterogeneity. The primary endpoints of interest are recurrence-free survival (RFS) and overall survival (OS). RESULT(S): A total of 14 studies included in qualitative synthesis and meta-analysis with a total of 5.294 patients were identified. Patients who had RT after radical hysterectomy was found to significantly have a more favorable RFS rate with OR 0.57 95% CI (0.38-0.84), p = 0.005; I2 = 63%. Nine studies were found comparing the OS between adjuvant RT and adjuvant CRT in a patient with ESCC with intermediate risk, the result is quite similar favoring adjuvant RT with significantly better OS outcome OR 0.69 95% CI (0.54-0.87), p = 0.002; I2 =34%. 1.526 had hematologic toxicities, 797 were RT and 729 had CRT. The study showed RT had better outcomes with lesser toxicities (OR 0.11, 95% CI [0.03-0.44] p = 0.002; I2 = 91%). Non-hematological toxicity, with a total of 1.463 patients, 799 were RT and 664 had CRT. Random models were used due to heterogeneity. RT is significantly associated with lesser non-hematologic toxicities with OR 0.34, 95% CI (0.18-0.66) p = 0.001; I2 = 65%. DISCUSSION: During the last two decades, there were significant changes in practice to cure uterine cervical cancer. Based on the consistent results generated in several previous randomized controlled trials, cisplatin-based CCRT has become the standard treatment for advanced cervical cancer. A randomized prospective studies by Sedlis et al., randomized FIGO IB patients without residual tumor or involved lymph nodes but with two or more intermediate-risk factors later named the "Sedlis criteria" to receive observation or RT following radical surgery. Adjuvant RT led to a reduction of recurrence rates at the cost of an approximately 4% higher rate of grade 3/4 adverse events. There was no increase in OS but an improvement of long-term RFS. On the other hand, a study found that RFS and OS were significantly improved in the addition of chemotherapy, especially in patients with clinical-stage IA2, IB, and IIA with para-metric invasion, residual tumor and/or lymph node involvement. This study found that RT had better outcomes in RFS and OS, RT also had lesser hematologic toxicity and non-hematologic toxicity. After all, it is prudent to take into account the adverse events as well as the QOL for long-term survivors. CONCLUSION(S): Adjuvant RT shows a better outcome in RFS and OS. CRT is often associated with greater hematological and non-hematological toxicities. Further high-quality randomized clinical trials with larger sample size comparing the efficacy and toxicity of adjuvant CRT with RT are recommended.Copyright © 2023 Gde Sastra Winata, William Alexander Setiawan, Putu Bagus Mulyana Yoga, Wayan Agus Surya Pradnyana, Stanly Kamardi, Putu Agung Satvika Pradnyadevi.

Winer, I., et al. (2023). "A Phase I/II, multicenter, open-label study of REGN5668 (R5668; mucin [MUC]16 x CD28 bispecific antibody [bsAb]) with cemiplimab or REGN4018 (R4018; MUC16 x CD3 bsAb) in patients with recurrent ovarian cancer (1309)." Gynecologic Oncology 176(Supplement 1): S190.
	Objectives: A high unmet need exists in recurrent ovarian cancer (rOVCA) treatment. R5668 and R4018 are human IgG4-based bispecific antibodies (bsAb) that bridge ovarian MUC16+ tumor cells to CD28 and CD3, respectively, expressed on T cells to stimulate cytotoxicity. Cemiplimab is a human monoclonal Ab that blocks programmed death (PD)-1 binding to PD-ligand(PD-L)1 and PD-L2. This first-in-human phase I/II study will assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of R5668 in combination with cemiplimab (Module 1) or in combination with R4018 (Module 2) in patients (pts) with rOVCA (NCT04590326). Method(s): This clinical trial will enroll up to 190 pts. with rOVCA. Inclusion criteria include histologically confirmed diagnosis of advanced epithelial ovarian (except carcinosarcoma), fallopian tube, or primary peritoneal cancer; serum CA-125 level >= 2x upper normal limit; and >= 1 prior treatment with platinum-based therapy. Exclusion criteria include approved conventional therapy <3 weeks (wks) (except biologics or immunotherapy) or investigational agents <4 wks or recent biologic therapy. This study includes a dose escalation (Bayesian optimal interval design) phase followed by an expansion phase. In Module 1, <=84 pts. will receive 3-4 wks of R5668 monotherapy lead-in at assigned intravenous (IV) weekly (QW) dose levels, followed by R5668 QW + cemiplimab IV every 3 wks. In Module 2, <=106 pts. will receive 4 wks of R4018 IV QW lead-in, followed by R4018 full QW dose + R5668 at the initial lead-in and full assigned QW doses. In the expansion phase, R5668 + cemiplimab and R5668 + R4018 combinations will each recruit 20 pts. in stage 1 and 30 pts. in stage 2 using a Simon two-stage design. In the escalation phase, primary endpoints include dose-limiting toxicities, serious and treatment-emergent adverse events (TEAEs), death, laboratory abnormalities (Grade >= 3), concentrations of R5668 in serum alone and in each combination regimen; the key secondary endpoint is objective response rate (ORR) per RECIST 1.1. In the expansion phase, the primary endpoint is ORR by RECIST 1.1 for each combination; key secondary endpoints are TEAEs, serious AEs, and deaths. Key exploratory endpoints are correlations between clinical efficacy endpoints and baseline protein expression levels of MUC16 and PD-L1.Copyright © 2023

Witz, C. A., et al. (2021). "Randomized, Assessor-Blinded Trial Comparing Highly Purified Human Menotropin and Recombinant Follicle-Stimulating Hormone in High Responders Undergoing Intracytoplasmic Sperm Injection." Obstetrical & gynecological survey 76(1): 34‐35.
	
Woelber, L., et al. (2020). "Targeted therapeutic approaches in squamous cell vulvar cancer (VSCC): Case series and review of the literature." Oncology Research.
	Therapeutic options in recurrent or metastasized VSCC not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 2013 - 2019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE-, Web of Science-, Scopus- and OVID database search was performed using the terms: 'vulvar cancer' AND 'targeted therapy', 'erlotinib', 'EGFR', 'bevacizumab', 'VEGF', 'pembrolizumab or 'immunotherapy'. 12/291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinum-based chemotherapy was applied to all patients (median 3.5 previous lines (range 2-5). In the erlotinib subgroup 2/5 patients (40%) achieved stable disease (SD) while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in 2nd/3rd line for a median of 3.4 months (range 2-6 months). Bevacizumab (n=9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9), best response was complete response (CR) (n=2/9 22.2%). Median duration of treatment was 7 months (range 4-13 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n=3) subset was SD (n=1/3 33%). Treatment was given as monotherapy in 2nd/3rd line for a median of 3.3 months (range 3-4 months). 9/12 patients (75%) experienced treatment-related AEs (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities, however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.

Woelber, L., et al. (2021). "Targeted therapeutic approaches in Vulvar Squamous Cell Cancer (VSCC): Case series and review of the literature." Oncology Research 28(6): 645-659.
	Therapeutic options in recurrent or metastasized vulvar squamous cell cancer (VSCC) not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 2013-2019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE, Web of Science, Scopus, and OVID database search was performed using the terms: "vulvar cancer" AND "targeted therapy," "erlotinib," "EGFR," "bevacizumab," "VEGF," "pembrolizumab," or "immunotherapy." Twelve of 291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinum-based chemotherapy was applied to all patients [median 3.5 previous lines (range 2-5)]. In the erlotinib subgroup, two of five patients (40%) achieved stable disease (SD), while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in second/third line for a median of 3.4 months (range 2-6 months). Bevacizumab (n = 9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9); best response was complete response (CR) (n = 2/9 22.2%). Median duration of treatment was 7 months (range 4-13 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n = 3) subset was SD (n = 1/3 33%). Treatment was given as monotherapy in second/third line for a median of 3.3 months (range 3-4 months). Nine of 12 patients (75%) experienced treatment-related adverse events (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities; however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.Copyright © 2021 Cognizant, LLC.

Woelber, L., et al. (2020). "Vulvar pruritus-causes, diagnosis and therapeutic approach." Deutsches Arzteblatt international 117(8): 126-133.
	Background: In Germany, 17-23% of the population suffers from chronic itching of the skin; in 5-10% of cases, the female genitalia are affected, specifically, the vulva. Vulvar pruritus is thus a common symptom that often markedly impairs the affected women's quality of life. Method(s): This review is based on pertinent publications that were retrieved by a selective search in MEDLINE/PubMed for articles on the pathogenesis, diagnosis, and treatment of vulvar pruritus. The search terms were (in German and English) "vulvarer Juckreiz," "pruritus vulvae," and "genital itch," alone and in combination with "Behandlung," "Therapie," or "treatment." Results: The most common cause of vulvar pruritus is vulvovaginal candidiasis followed by chronic dermatoses, such as lichen sclerosus and vulvar eczema. Especially in refractory cases, an invasive or preinvasive lesion such as squamous epithelial dysplasia (VIN, vulvar intraepithelial neoplasia) should be borne in mind in the differential diagnosis. Rarer causes include infection, atrophy, and vulvodynia. The essential elements of treatment are topical/oral antimycotic drugs and high-potency glucocorticoids, along with consistently applied, basic moisturizing care and the avoidance of potential triggering factors. Conclusion(s): As vulvar pruritus has multiple causes, standardization of its diagnostic evaluation and treatment would be desirable, both to achieve optimal efficacy and to meet the diverse needs of women who suffer from this condition.Copyright © 2020 Deutscher Arzte-Verlag GmbH. All rights reserved.

Wojcik, M., et al. (2023). "The Application of Physiotherapy in Urinary Incontinence." Clinical and Experimental Obstetrics and Gynecology 50(1): 7.
	Objective: The problem of urinary incontinence affects half of the adult female population, impacting adversely on their comfort of life and significantly hindering ordinary life activities (laughing, sneezing, coughing, physical activity) it also affects the quality of their sexual life. Physiotherapy is an increasingly common method for the conservative treatment of genital static disorders and stress urinary incontinence. Mechanism: In this article, the authors consider the following aspects: the use of various physiotherapy interventions as adjunctive treatment for urinary incontinence. The authors reviewed the literature databases in PubMed, Medline and Embase to identify links between the applied physiotherapeutic treatment and its effectiveness. Findings in Brief: The applied physiotherapeutic treatments and their effectiveness in urinary incontinence are presented. Conclusion(s): Physiotherapy treatments are effective and supportive of the treatment process in women of all age ranges with urinary incontinence, thus improving their quality of life.Copyright © 2023 The Author(s). Published by IMR Press.

Wolf, J. P. (2022). "Le « Conte de la Bonne Aventure » ou la 4e révolution de l'AMP." Morphologie : bulletin de l'Association des anatomistes 106(354): S3‐S4.
	La qualité ovocytaire est le facteur strictement limitant du taux de naissance aussi bien en procréation naturelle, qu'en AMP. Un couple jeune, fertile, n'a que 23 % de chance de concevoir par cycle, la femme, jeune, ne produisant que 2 ovocytes par an susceptibles de supporter une grossesse. Pour identifier le récepteur ovocytaire du spermatozoïde nous avons synthétisé une molécule reproduisant le site de fixation de la protéine de membrane spermatique ADAM2, pour réaliser une inhibition compétitive de la fécondation. Mais, cette molécule, au lieu d'inhiber la fécondation, a multiplié l'index de fusion des ovocytes humains par 2. Son action a donc été étudiée sur le sperme, sur l'ovocyte et l'embryon humain. Elle améliore les paramètres du mouvement [1]. Elle amélioration le taux de maturation des ovocytes, mais surtout, elle entraîne une amélioration de la ségrégation des chromosomes au cours de la méiose I et augmente le taux des ovocytes en M II euploïdes [2]. Sur l'embryons humain donné pour la recherche nous avons montré, à partir d'embryons j2, qu'elle stimule la blastoformation, augmente le nombre de cellules de leur trophoblaste et multiplie par 3 l’éclosion des blastocystes [3]. Dans une étude Clinique (Clinical.gov : NCT02161861), nous avons montré, par la prise en charge de 66 couples, dont la cohorte ovocytaire a été répartie en deux groupes de façon randomisée, et inséminée avec le sperme du conjoint en présence ou non de la molécule, une chute des taux de fausses couches et une augmentation du nombre de bébés nés passant de 27,9 % au premier transfert chez les femmes de moins de 37 ans à 62,3 % pour les embryons incubés avec la molécule. La molécule, brevetée par l'AP–HP est actuellement testée dans un essai de Phase 3 pour lequel l'AP–HP est promoteur (Clinicaltrial.gov : NCT04954274).

Wolff, J., et al. (2023). "Digital therapeutic to improve cancer-related well-being: a pilot randomized controlled trial." International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 33(7): 1118-1124.
	Objective: This randomized waitlist controlled pilot study aimed to evaluate the feasibility and preliminary efficacy of Mika, an app-based digital therapeutic intervention hypothesized to improve management and the support of cancer patients.; Methods: Patients with gynecological malignancies undergoing post-operative or routine outpatient chemotherapy were randomized (5:2) into intervention (Mika plus treatment-as-usual) and control (treatment-as-usual alone). Feasibility outcomes including dropout rate, reasons for dropout, and intervention adherence, as well as efficacy outcomes including depression, fatigue, and health literacy were assessed at baseline, 4, 8, and 12 weeks. Changes in efficacy outcomes from baseline to week 12 were evaluated in the intervention group only by means of Wilcoxon signed-rank tests.; Results: Seventy participants (intervention group, n=50; control group, n=20) with gynecological cancer (ovarian, cervical, and endometrial) were randomized. The dropout rate increased from 15.7% (11/70) between baseline and week 4 to 37.1% (26/70) between weeks 8 and 12. Primary reasons for dropout were death (n=10) and health status deterioration (n=11). The initial high intervention adherence observed between baseline and week 4 (86% usage rate, average usage time: 120 min, average number of logins: 16.7) declined in weeks 8 to 12 (46% usage rate, average usage time: 41 min, average number of logins: 9). Participants in the intervention group showed significant intra-individual reductions in depressive symptoms by 42% ( d =0.85) and fatigue symptoms by 23.1% ( d =0.5) from baseline to 12 weeks.; Conclusions: This pilot study provides initial evidence of the feasibility and efficacy of Mika in improving the well-being of cancer patients. The high initial intervention adherence and significant reductions in depressive and fatigue symptoms suggest that Mika has the potential to improve the management and support of cancer patients.; Trial Registration: German Clinical Trials Register (DRKS) ID: DRKS00023791; retrospectively registered on February 24, 2022.; Competing Interests: Competing interests: Co-authors JSR and GF are the two co-founders and managing directors of Fosanis GmbH, the company that developed the Mika app and funded the present research. Co-authors AM and MF are employees of Fosanis GmbH. All the other authors declare that they have no conflicts of interest. (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Wolff, J., et al. (2021). "Digital health-related app supporting patients with gynaecological malignancies: results of a feasibility trial." International Journal of Gynecological Cancer 31(SUPPL 1): A376.
	Introduction/Background To investigate the feasibility and acceptance of the Mika health app by patients with cancer. Methodology Prospective intra‐individually controlled pilot study. Patients were randomly assigned to receive either digital psycho‐oncological support in the form of the app or standard care. Result(s) A total of 70 patients were included, one‐third of whom had high levels of psychological distress. Relative to the baseline during the 12‐week period, the mean depression score decreased in the intervention group (p = 0.00078 one‐tailed, p = 0.0016 two‐tailed), without any changes in the control group. The most prevalent disease‐specific side effect was fatigue, which decreased by 23.1% in the intervention group and by 31.1% in the chemotherapy subgroup (p = 0.02). Conclusion The digital app showed high acceptance and satisfaction among patients with gynaecological malignancies, regardless of age group.

Wolters, V. E. R. A., et al. (2021). "Placental pathology in cancer during pregnancy and after cancer treatment exposure." Placenta 111: 33-46.
	Cancer during pregnancy has been associated with (pathologically) small for gestational age offspring, especially after exposure to chemotherapy in utero. These infants are most likely growth restricted, but sonographic results are often lacking. In view of the paucity of data on underlying pathophysiological mechanisms, the objective was to summarize all studies investigating placental pathology related to cancer(treatment). A systematic search in PubMed/Medline, Embase (OVID) and SCOPUS was conducted to retrieve all studies about placental pathology in cancer during pregnancy or after cancer treatment, published until August 2020. The literature search yielded 5784 unique publications, of which 111 were eligible for inclusion. Among them, three groups of placental pathology were distinguished. First, various histopathologic changes including maternal vascular malperfusion have been reported in pregnancies complicated by cancer and after cancer treatment exposure, which were not specific to type of cancer(treatment). Second, cancer(treatment) has been associated with placental cellular pathology including increased oxidative damage and apoptosis, impaired angiogenesis and genotoxicity. Finally, involvement of the placenta by cancer cells has been described, involving both the intervillous space and rarely villous invasion, with such fetuses are at risk of having metastases. In conclusion, growth restriction is often observed in pregnancies complicated by cancer and its cause can be multifactorial. Placental histopathologic changes, cellular pathology and genotoxicity caused by the cancer(treatment) may each play a role.Copyright © 2021 The Authors

Wong, K. M., et al. (2021). "Transfer of fresh or frozen embryos: a randomised controlled trial." Human reproduction (Oxford, England) 36(4): 998‐1006.
	STUDY QUESTION: Is IVF with frozen‐thawed blastocyst transfer (freeze‐all strategy) more effective than IVF with fresh and frozen‐thawed blastocyst transfer (conventional strategy)? SUMMARY ANSWER: The freeze‐all strategy was inferior to the conventional strategy in terms of cumulative ongoing pregnancy rate per woman. WHAT IS KNOWN ALREADY: IVF without transfer of fresh embryos, thus with frozen‐thawed embryo transfer only (freeze‐all strategy), is increasingly being used in clinical practice because of a presumed benefit. It is still unknown whether this new IVF strategy increases IVF efficacy. STUDY DESIGN, SIZE, DURATION: A single‐centre, open label, two arm, parallel group, randomised controlled superiority trial was conducted. The trial was conducted between January 2013 and July 2015 in the Netherlands. The intervention was one IVF cycle with frozen‐thawed blastocyst transfer(s) versus one IVF cycle with fresh and frozen‐thawed blastocyst transfer(s). The primary outcome was cumulative ongoing pregnancy resulting from one IVF cycle within 12 months after randomisation. Couples were allocated in a 1:1 ratio to the freeze‐all strategy or the conventional strategy with an online randomisation programme just before the start of down‐regulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were subfertile couples with any indication for IVF undergoing their first IVF cycle, with a female age between 18 and 43 years. Differences in cumulative ongoing pregnancy rates were expressed as relative risks (RR) with 95% CI. All outcomes were analysed following the intention‐to‐treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Two‐hundred‐and‐five couples were randomly assigned to the freeze‐all strategy (n = 102) or to the conventional strategy (n = 102). The cumulative ongoing pregnancy rate per woman was significantly lower in women allocated to the freeze‐all strategy (19/102 (19%)) compared to women allocated to the conventional strategy (32/102 (31%); RR 0.59; 95% CI 0.36‐0.98). LIMITATIONS, REASONS FOR CAUTION: As this was a single‐centre study, we were unable to study differences in study protocols and clinic performance. This, and the limited sample size, should make one cautious in using the results as the basis for definitive policy. All patients undergoing IVF, including those with a poor prognosis, were included; therefore, the outcome could differ in women with a good prognosis of IVF treatment success. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that there might be no benefit of a freeze‐all strategy in terms of cumulative ongoing pregnancy rates. The efficacy of the freeze‐all strategy in subgroups of patients, different stages of embryo development, and different freezing protocols needs to be further established and balanced against potential benefits and harms for mothers and children. STUDY FUNDING/COMPETING INTEREST(S): The Netherlands Organisation for Health Research and Development (ZonMW grant 171101007). S.M., F.M. and M.v.W. stated they are authors of the Cochrane review 'Fresh versus frozen embryo transfers in assisted reproduction'. TRIAL REGISTRATION NUMBER: Dutch Trial Register, NTR3187. TRIAL REGISTRATION DATE: 9 December 2011. DATE OF FIRST PATIENT’S ENROLMENT: 8 January 2013.

Wong Tin, L., et al. (2021). "Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention." Seminars in cancer biology 73: 265-293.
	Cancer remains to be the second highest cause of mortality in our society, falling just short of heart disease. Despite major advancement in cancer therapy over the past decade, momentum has been gaining for an alternative approach of using naturally-occurring and dietary agents for cancer prevention and management. Research on pomegranate (Punica granatum L.), a fruit of the Punicaceae family, has shown enormous potential for cancer prevention and intervention. In addition to a rich source of polyphenols, including flavonoids and ellagitannins, in its juice, pomegranate also houses hundreds of other phytochemicals in its pericarp, seed, flower, bark, flowers and leaves. These phytochemicals provide powerful antiproliferative, anti-inflammatory, antioxidant, anti-invasive, antimigratory, anti-angiogenic and anti-metastatic effects without significant toxicity. This makes the use of its various extracts a very attractive strategy to our current battle against cancer. This review article presents a systematic, comprehensive and critical review of research on pomegranate-derived products in both cancer prevention and intervention. It discusses the chemical constituents of pomegranate, the results of both preclinical (in vitro, ex vivo and in vivo) and clinical studies on the anticancer effect of pomegranate phytochemicals and molecular targets in numerous types of cancers, such as breast, gastrointestinal tract (oral, colon, liver and pancreas), gynecological (uterine and ovarian), hematological (lymphoma, leukemia and myeloma), lung, neurological (glioma), urogenital (bladder and prostate), bioavailability, pharmacokinetics and safety of pomegranate constituents. In order to guide the direction of future research, we have also included current limitations and challenges in the field and our post analysis recommendation. (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Woo Hye, L., et al. (2020). "Efficacy and safety of herbal medicine (Dangguijagyag-san) for primary dysmenorrhea: study protocol for a randomized, double-blind, placebo-controlled, parallel-group, multi-center trial." Integrative Medicine Research 9(2): 100394.
	Background: Dangguijagyag-san, also known as Dangguishaoyao-san in Chinese and Toki-shakuyakui-san in Japanese, has been frequently used to treat symptoms associated with dysmenorrhea. The purpose of this trial is to evaluate the efficacy and safety of the herbal medicine, Dangguijagyag-san, relative to those of active control, Gamisoyo-san, and a placebo control for primary dysmenorrhea.; Methods: This protocol details a randomized, double-blind, parallel-group, multi-center, investigator-initiated, controlled trial evaluating treatment of primary dysmenorrhea. Two hundred and forty participants will be randomly divided into one of three groups: 1) the Dangguijagyag-san experimental group (EG) (n = 105), 2) the Gamisoyo-san active control group (ACG) (n = 30), and 3) the placebo control group (PCG) (n = 105). The interventions will be administered for two menstrual cycles, and the follow-up will be carried out for the following six menstrual cycles. The primary outcomes are difference in response rates between the EG and the ACG (non-inferiority comparison) and difference in changes from baseline in average pain intensity measured by the visual analogue scale between the EG and PCG (superiority comparison). The secondary outcomes are pain scores derived from pain assessment tools (verbal multidimensional scoring system, retrospective symptom scale, and short form McGill pain questionnaire), dosage of analgesics, pattern diagnosis questionnaires, and short form 36 health survey. Adverse events and vital signs will be checked at every visit, and laboratory tests will be performed for safety evaluation.; Discussion: The results of this clinical trial will offer evidence for the efficacy and safety of Dangguijagyag-san for primary dysmenorrhea.; Trial Registration: Clinical Research Information Service of Korea: KCT0003005. (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

Woodis, C. B., et al. (2021). "Bioidentical Oral 17beta-Estradiol and Progesterone for the Treatment of Moderate to Severe Vasomotor Symptoms of Menopause." Annals of Pharmacotherapy 55(9): 1153-1158.
	Objective: To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17beta-estradiol/progesterone (17beta-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus. Data Sources: Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva. Study Selection and Data Extraction: All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included. Data Synthesis: In 1 phase 3 clinical study, 17beta-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population. Relevance to Patient Care and Practice: Concerns over content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration-regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17beta-E/P is approved for the treatment of VMS associated with menopause. Conclusion(s): 17beta-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms.Copyright © The Author(s) 2020.

Woodward, A., et al. (2019). "The effects of exercise on cardiometabolic outcomes in women with polycystic ovary syndrome not taking the oral contraceptive pill: protocol for a systematic review and meta-analysis." Systematic Reviews 8(1): 116.
	Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy, affecting 4-12% of reproductive-aged women. Women with PCOS often exhibit many metabolic abnormalities that are associated with an increased cardiovascular disease (CVD) risk, independent of obesity. Exercise interventions from 12 to 24 weeks have been shown to have positive effects on blood lipid profile, ovulation and insulin resistance in women with PCOS. However, no consensus on which exercise interventions are effective (i.e. duration, type of exercise, frequency), including for different phenotypes, currently exists. The aim of this systematic review and meta-analysis is to define effective types of exercise interventions to improve cardiometabolic profile, across the range of phenotypes of PCOS.; Methods: We will conduct electronic database searches, including randomised-controlled trials (RCT), quasi-RCT and clinical trials. Primary outcomes sought will be lipid profile, carotid-intima media thickness, fasting blood glucose, %HbA1c, blood pressure, waist circumference, waist-to-hip ratio, abdominal adiposity and inflammation markers. Secondary outcomes sought will be free and total testosterone, sex hormone binding globulin and insulin resistance. The Cochrane Risk Assessment Tool will be used to assess study quality. Data will be analysed in RevMan. Analysis of heterogeneity will be undertaken using the I 2 statistic. Significant heterogeneity will be explored, and sensitivity analyses carried out as appropriate. A subgroup analysis based on androgen profile will be undertaken if data are sufficient.; Discussion: A large proportion of women are affected by PCOS. It is prudent to examine how CVD risk can be mitigated in this high-risk population, and this review aims to provide evidence-driven recommendations on the types of exercise interventions that are effective for this. The review will seek to provide recommendations regarding type, frequency and duration of exercise interventions to improve cardiometabolic profile in PCOS. The subgroup analysis may be able to highlight difference in intervention effects between normo-androgenic and hyper-androgenic profile. Limitations include heterogeneity across studies and a scarcity of clinical trials involving a PCOS control group not undertaking any intervention.; Systematic Review Registration: PROSPERO CRD42018086117.

Woon Ee, V., et al. (2020). "Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis." Journal of Reproductive Immunology 142: 103189.
	There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79-3.69; p < 0.05), however there were significant heterogeneity (I 2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.; Competing Interests: Declaration of Competing Interest The authors report no declarations of interest. (Copyright © 2020 Elsevier B.V. All rights reserved.)

Wright, D., et al. (2022). "A Review of GnRH Antagonists as Treatment for Abnormal Uterine Bleeding-Leiomyoma (AUB-L) and Their Influence on the Readiness of Service Members." Military medicine.
	Introduction: Not too long ago, Lupron Depot® (leuprolide acetate), an injectable gonadotropin-releasing hormone (GnRH) agonist, was the only Food and Drug Administration (FDA) approved GnRH analog used to clinically treat abnormal uterine bleeding associated with uterine leiomyoma (AUB-L) when second-line medical management was warranted; however, the FDA has now approved elagolix and relugolix, GnRH antagonists, to be treatment options as well. This is a review of GnRH antagonists for the management of uterine fibroids reviewing their treatment efficacy, side effect profile, and current use in military medicine.; Methods: This is a review of studies from multiple electronic databases (Pubmed, ACOG, FDA, U.S. Military Guidelines) published between 1990 and 2021. Keywords used for the search include GnRH antagonist, elagolix, relugolix, uterine leiomyoma, and abnormal uterine bleeding. Our inclusion criteria for articles reviewed were: systematic reviews with the listed keywords, multicenter randomized trials, and meta-analyses. The DODI on Medical Standards for Medical Service, Air Force Aerospace Medicine Waiver Guide, Navy Guidance Aeromedical Reference and Waiver Guide, and the Army Regulation 40-501 Standards of Medical Fitness were used to review the military standards and current restrictions placed on service members.; Results: Thirty-three articles were reviewed and summarized.; Conclusion: Uterine leiomyoma can impact service members' eligibility and fitness for duty. The oral administration of elagolix and relugolix adds convenience to this drug class through its oral administration while lengthening the duration of treatment up to 24 months. All military medical facilities should advocate for the well-being of their service members by stocking all options available. Health care providers should collaborate with patients in making the best therapy choice that is suited for their lifestyle and military occupation. (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Wu, C., et al. (2021). "Effects of unsupervised behavioral and pelvic floor muscle training programs on nocturia, urinary urgency, and urinary frequency in postmenopausal women: Secondary analysis of a randomized, two-arm, parallel design, superiority trial (TULIP study)." Maturitas 146: 42-48.
	OBJECTIVE: To determine and compare the effects of an unsupervised behavioral and pelvic floor muscle training (B-PFMT) program delivered in two formats on nocturia, urinary urgency, and urinary frequency in postmenopausal women. STUDY DESIGN: A secondary analysis used data collected from women enrolled in the TULIP study. Women aged 55 years or more with no urinary incontinence were provided the B-PFMT program. Each woman was randomly assigned to a face-to-face class that took about 2 h (2-hrClass) or to a DVD showing essentially the same information as a 20-minute video (20-minVideo). All women were instructed to independently continue the program following their education session. Three urinary outcomes were assessed at baseline, 3, 12, and 24 months. MAIN OUTCOME MEASURES: Nocturia and urinary urgency were examined with one item each from the questionnaire-based voiding diary, and urinary frequency was assessed with patients' self-documenting 3-day bladder diary. RESULTS: Women in the 2-hrClass group experienced significantly fewer nocturia episodes and longer average inter-void interval at each follow-up and fewer urinary urgency episodes at 12 months. Women in the 20-minVideo group experienced significantly fewer episodes of nocturia and urinary urgency and longer average inter-void interval at each follow-up time point. No significant between-group differences were found for any outcome, except for nocturia at 24 months, when effectiveness favored women in the 20-minVideo group. CONCLUSIONS: Unsupervised B-PFMT programs are effective for improving postmenopausal women's urinary outcomes regardless of the format. The optimal format to deliver B-PFMT programs in terms of effectiveness should be explored in future studies.

Wu, C., et al. (2020). "Unsupervised behavioral and pelvic floor muscle training programs for storage lower urinary tract symptoms in women: a systematic review." International Urogynecology Journal 31(12): 2485-2497.
	Introduction and hypothesis: This study synthesized the effects of unsupervised behavioral and pelvic floor muscle training (B-PFMT) programs on outcomes relevant to women's storage lower urinary tract symptoms (LUTS) and pelvic floor muscle strength (PFMS). Method(s): PubMed, CINAHL, Web of Science, and PsycINFO were searched since their inception to August 6, 2019. Randomized controlled trials (RCTs) and quasi-experimental articles that enrolled community women aged 18 years and older and reported storage LUTS outcomes including symptoms, severity, impact, self-reported symptom improvement, and PFMS were screened and extracted. Risk of bias was evaluated, and a narrative synthesis approach was used to synthesize evidence. Result(s): Ten RCTs and three pretest-posttest articles were retrieved. Half of the RCTs had some concerns of bias; the remaining RCTs had high risk of bias. Three pretest-posttest articles had at least some risk of bias. Ten articles aimed to treat urinary incontinence (UI) primarily in middle-aged women, two aimed to prevent UI, and one aimed to improve PFMS in young continent women. Two months post-intervention, UI treatment effectiveness was observed, and cumulative effectiveness was evident in: (1) reduction in the number of incontinent episodes, (2) reduction in the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form and International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life scores, (3) increased patients' global impression of improvement, and (4) improvement of PFMS. Conclusion(s): Unsupervised B-PFMT programs improve outcomes relevant to UI and PFMS in midlife community women who have UI. Their effects on UI prevention and other storage LUTS remain unclear.Copyright © 2020, The International Urogynecological Association.

Wu Clara, Q., et al. (2019). "Live Birth Rate after Surgical and Expectant Management of Endometriomas after In Vitro Fertilization: A Systematic Review, Meta-Analysis, and Critical Appraisal of Current Guidelines and Previous Meta-Analyses." Journal of Minimally Invasive Gynecology 26(2): 299.
	Controversy exists regarding surgical management of endometriomas in infertile women before in vitro fertilization (IVF) because growing evidence indicates that surgery may impair the ovarian response. The objective of the present systematic review and meta-analysis was to compare surgical and expectant management of endometriomas regarding IVF outcomes. Prospective and retrospective controlled studies were found via the Cochrane Library, Embase, and MEDLINE databases. Thirteen studies (1 randomized controlled trial and 12 observational studies, N = 2878) were pooled, and similar live birth rates were observed in the surgically and expectantly managed groups (odds ratio = 0.83; 95% confidence interval [CI], 0.56-1.22; p = .98). The clinical pregnancy rates (odds ratio = 0.83; 95% CI, 0.66-1.05; p = .86), the number of mature oocytes retrieved, and the miscarriage rates were not statistically different between study groups. However, the total number of oocytes retrieved was lower in the surgery group (mean difference = -1.51; 95% CI, -2.60 to -0.43; p = .02). Findings suggest that surgical management of endometriomas before IVF therapy yields similar live birth rates as expectant management. However, future properly designed randomized controlled trials are warranted. (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Wu, D., et al. (2022). "Comparison of the Effectiveness of Various Medicines in the Prevention of Ovarian Hyperstimulation Syndrome: A Network Meta-Analysis of Randomized Controlled Trials." Frontiers in Endocrinology 13: 808517.
	Background: Previous studies have described the effects of different drugs in preventing ovarian hyperstimulation syndrome (OHSS). However, the efficacies of those drugs in preventing OHSS remain inconclusive.; Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. A network meta-analysis of randomized controlled trials (RCTs) was performed up to August 2021. We investigated the following drugs in our study: aspirin, albumin, metformin, calcium, cabergoline, quinagolide, letrozole, hydroxyethyl starch (HES), and glucocorticoids. The primary outcome was the incidence rate of moderate-to-severe OHSS, with the results presented as risk ratios (RRs) with 95% confidence intervals (CIs).; Results: The incidence of moderate-to-severe OHSS was significantly reduced by calcium administration (risk ratios [RR] 0.14, 95% confidence interval [CI]: 0.04, 0.46) (grade: high), HES (RR 0.25, 95% CI 0.07, 0.73) (grade: high), and cabergoline (RR 0.43, 95% CI 0.24, 0.71) (grade: moderate). The surface under the cumulative ranking curve (SUCRA) indicated that calcium (SUCRA, 92.4%) was the most effective intervention for preventing moderate-to-severe OHSS. These drugs were safe and did not affect clinical pregnancy, miscarriage, or live birth rates.; Conclusion: Calcium, HES, and cabergoline could effectively and safely prevent moderate-to-severe OHSS, with calcium as the most effective intervention.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Wu, Shi, Yu, Yu and Zhai.)

Wu, G. and H. Zhao (2019). "Gonadotropin-releasing hormone agonists for the protection of ovarian function in premenopausal patients treated by chemotherapy: a meta-analysis." Cancer Research and Clinic 31(8): 545-560.
	Objective To evaluate systematically the effectiveness of gonadotropin-releasing hormone agonist (GnRHa) administration before chemotherapy and/or during chemotherapy for the protection of ovarian function in premenopausal women. Methods PubMed, Cochrane Lihrary, Medline, Embase, China Biomedical Literature Database, CNKI were searched to collect the clinical randomized control trail (RCT) of ovarian function protection in premenopausal women receiving chemotherapy by using GnRHa. RevMan5.3 software was used to analyze the incidence of early premature ovarian insufficiency (POI), menstrual recovery rate, pregnancy rate and other indicators. Results A total of 12 articles were included, including a total of 1 509 premenopausal women who received chemotherapy for malignant diseases. GnRHa combined with chemotherapy reduced the incidence of POI (OR = 0.36, 95% CI 0.23-0.56, P < 0.01) and improved the menstrual recovery rate during follow-up (OR = 2.49, 95% CI 1.72-3.60, P < 0.01). GnRHa combined with chemotherapy could increase the pregnancy rate of patients aged 35 years and older (OR 2.04, 95% CI 1.08-3.83, P- 0.03). Conclusion GnRHa administration before chemotherapy and/or during chemotherapy may prevent the chemotherapy damage to ovarian function, reduce the incidence of POI, and improve the recovery rate of menstruation.Copyright © 2019 Chinese Medical Association Publishing House Co. Ltd. All rights reserved.

Wu, H., et al. (2019). "Vaginal endometrial stromal sarcoma: A literature review." European Journal of Obstetrics and Gynecology and Reproductive Biology: X 4: 100094.
	Vaginal endometrial stromal sarcoma (VESS) is a rare disease. To the best of our knowledge, there have only been a few reported cases in the literature. Therefore, we conducted a literature review to obtain specific knowledge of this disease. Thirteen cases of VESS were found by searching the Medline and EMBASE databases in the English language. The mechanism of VESS may be associated with endometriosis, and its diagnosis largely depends on pathological examination because it has no typical symptoms. Treatment of VESS incorporates surgery, chemotherapy, radiotherapy, and hormonal therapy. Some novel drugs targeting its mechanism may become alternative therapies. Its prognostic factors may include tumor stage and the expression of hormonal receptors.Copyright © 2019 The Authors

Wu, H., et al. (2021). "Luteal phase support for in vitro fertilization/intracytoplasmic sperm injection fresh cycles: a systematic review and network meta-analysis." Reproductive biology and endocrinology : RB&E 19(1): 103.
	Background: Various luteal phase supports (LPSs) have been proven to increase the pregnancy rate in fresh cycles of in vitro fertilization or intracytoplasmic sperm injection; however, there is still significant debate regarding the optimal use of LPS.; Methods: A systematic review with the use of a network meta-analysis was performed via electronic searching of Ovid MEDLINE, the Cochrane Library, Embase, Web of Science, ClinicalTrials.gov and Google Scholar (up to January 2021) to compare the effectiveness and safety of various LPSs, as well as to evaluate the effects of different initiations of LPSs on pregnancy outcomes. The primary outcomes included live birth and ongoing pregnancy, with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs).; Results: Eighty-nine randomized controlled trials with 29,625 women comparing 14 interventions or placebo/no LPS treatments were included in the meta-analyses. No significant differences were found in terms of the pregnancy outcomes when LPS was started within 48 h after oocyte retrieval versus a delayed initiation between 48 h and 96 h after oocyte retrieval. The addition of gonadotropin-releasing hormone (GnRH) agonists to progesterone vaginal pessaries showed a significant benefit in terms of live birth (OR 1.39, 95% CI 1.08 to 1.78). Only human chorionic gonadotropin (HCG) was found to be more efficacious than the placebo/no LPS treatment in terms of live birth (OR 15.43, 95% CI 2.03 to 117.12, low evidence). Any active LPSs (except for rectal or subcutaneous progesterone) was significantly more efficacious than the placebo/no LPS treatment in terms of ongoing pregnancy, with ORs ranging between 1.77 (95% CI 1.08 to 2.90) for the vaginal progesterone pessary and 2.14 (1.23 to 3.70) for the intramuscular progesterone treatment. Among the comparisons of efficacy and tolerability between the active treatments, the differences were small and very uncertain.; Conclusion: Delays in progesterone supplementation until 96 h after oocyte retrieval does not affect pregnancy outcomes. The safety of GnRH agonists during the luteal phase needs to be evaluated in future studies before the applications of these agonists in clinical practice. With comparable efficacy and acceptability, there may be several viable clinical options for LPS.

Wu, J., et al. (2021). "Less radical surgery for early-stage cervical cancer: a systematic review." American Journal of Obstetrics and Gynecology 224(4): 348.
	Objective: A systematic review was performed to examine the outcomes of simple hysterectomy for women with low-risk, early-stage cervical cancer.; Data Sources: MEDLINE, Embase, Web of Science, and ClinicalTrials.gov were searched from inception until November 4, 2020.; Study Eligibility Criteria: Original research reporting recurrence or survival outcomes among women with early-stage cervical cancer (defined as stage IA2 to IB1 disease) who were treated with simple hysterectomy.; Methods: Data regarding study characteristics, tumor characteristics, other treatment modalities, adjuvant therapy, recurrence, and survival outcomes were analyzed. Studies that reported both simple hysterectomy and radical hysterectomy outcomes were compared in a subgroup analysis. Summary statistics were reported and eligible studies were further analyzed to determine an estimated hazard ratio comparing simple hysterectomy with radical hysterectomy.; Results: A total of 21 studies were included, of which 3 were randomized control trials, 14 retrospective studies, 2 prospective studies, and 2 population-level data sets. The cohort included 2662 women who underwent simple hysterectomy, of which 36.1% had stage IA2 disease and 61.0% stage IB1 disease. Most cases (96.8%) involved tumors of ≤2 cm in size, and 15.4% of cases were lymphovascular space invasion positive. Approximately 71.8% of women who underwent simple hysterectomy had a lymph node assessment, and 30.7% of women underwent adjuvant chemotherapy or radiation. The most common complications described were lymphedema (24%), lymphocysts (22%), and urinary incontinence (18.5%). The total death rate for studies that reported deaths was 5.5%. By stage, there was a 2.7% mortality rate among IA2 disease and a 7.3% mortality rate among IB1 disease. Of note, 18 studies reported outcomes for both simple and radical hysterectomy, with a 4.5% death rate in the radical hysterectomy group and a 5.8% death rate in the simple hysterectomy group. Estimated and reported hazard ratio demonstrated no significant association for mortality between radical and nonradical surgeries for IA2 disease but potentially increased risk of mortality among IB1 disease. All studies had a moderate to high risk of bias, including the 3 randomized control trials. Level of evidence was limited to III to IV.; Conclusion: The use of less radical surgery for women with stage IA2 and small volume IB1 cervical cancers appears favorable. However, there is concern that simple hysterectomy in women with stage IB1 tumors may adversely impact survival. Overall, the quality of studies available is modest, limiting the conclusions that can be drawn from the available literature. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Wu, J., et al. (2021). "Outcomes of reproduction following cesarean scar pregnancy treatment: A systematic review and meta-analysis." European Journal of Obstetrics, Gynecology, and Reproductive Biology 262: 80-92.
	Objectives: To explore the reproductive outcomes of women with a history of cesarean scar pregnancy (CSP) and the influence of various treatments on subsequent pregnancy outcomes.; Study Design: The PubMed, Embase, Medline, Cochrane Library and ClinicalTrial.gov databases were searched for studies with the outcomes of pregnancy after CSP treatment. Studies that reported reproductive outcomes after CSP with more than 5 followed cases were included. The main data collected includes the treatment methods of CSP and subsequent pregnancy outcomes. The main information includes intrauterine pregnancy, recurrent CSP (RCSP), and spontaneous miscarriage, while the secondary information includes complications during pregnancies and the outcomes of childbirths. According to different treatments (conservative treatment, surgical treatment without resection of cesarean scar, and surgical treatment with resection of cesarean scar), a stratified analysis was carried out to compare the influence of treatments on subsequent pregnancy outcomes.; Results: A total of 32 studies including 3380 cases of CSP met the inclusion criteria, of which 583 cases conceived again after treatment (including 292 cases of unexpected pregnancy), and finally 178 cases delivered successfully. The follow-up time ranged from 3 to 72 months. Among women with fertility requirements, a total of 291 cases in 403 women were successfully conceived during the follow-up period in 15 studies. Thence the pregnancy rate of women with fertility requirements was 76.2 %. Among all of the 583 successfully conceived women, 83.4 % of them had intrauterine pregnancy, while 15.3 % of cases were RCSP. The total ectopic pregnancy rate reached 16.6 %, covering RCSP and other sites of ectopic pregnancy. 14.6 % of intrauterine pregnancy experienced spontaneous miscarriage. The intrauterine pregnancy rates of the conservative treatment group, the surgical treatment without resection of cesarean scar group, and the surgical treatment with resection of cesarean scar group were 93.1 %, 80.1 % and 86.0 % respectively; the corresponding RCSP rates were 6.9 %, 15.6 % and 14.0 % respectively; and the corresponding spontaneous miscarriage rates were 20.7 %, 13.9 % and 22.2 % respectively.; Conclusion: The outcomes of reproduction after CSP included intrauterine pregnancy, RCSP and other sites of ectopic pregnancy. Women with a history of CSP still have a high pregnancy rate, but the risk of RCSP and spontaneous miscarriage is also increased. It is impossible to clarify the effect of different treatments on subsequent pregnancy. Whether the resection and repair of cesarean scar can ameliorate reproductive outcomes needs to be further assessed. Further large-scale prospective studies, even RCTs with long-term follow-up are needed to expound the outcomes of reproduction after CSP and the effect of different treatments on subsequent reproductive outcomes.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Wu, J., et al. (2019). "Laparoscopic nerve-sparing radical hysterectomy versus laparoscopic radical hysterectomy in cervical cancer: a systematic review and meta-analysis of clinical efficacy and bladder dysfunction." Journal of Minimally Invasive Gynecology 26(3): 417-417.
	It is widely accepted that nerve-sparing radical hysterectomy is associated with less postoperative morbidity than is observed in radical hysterectomy, while clinical safety is similar between the two. However, there is insufficient evidence to compare the laparoscopic approaches to these procedures. We performed a systematic review and meta-analysis to compare clinical efficacy and the rate of bladder dysfunction, including urodynamic assessment, between laparoscopic nerve-sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH). Thirty articles including 2743 participants were included. Operating times were shorter (MD=29.88 min, 95% CI=11.92 to 47.83) and hospital stays longer (MD=-1.56 d, 95% CI=-2.27 to -0.84) in LRH than in LNSRH. In addition, blood loss and the number of resected lymph nodes were not significantly different between the two. However, resected parametrium lengths (MD=-0.02 cm, 95% CI=-0.05 to -0.00) and vaginal cuff widths (MD=-0.06 cm, 95% CI=-0.09 to -0.04) were smaller in LNSRH. Furthermore, LNSRH tended to result in more satisfactory micturition (OR=2.90, 95% CI=2.01 to 4.19), shorter catheterization times (MD=-7.20 d, 95% CI=-8.10 to -6.29) and shorter recovery to normal post-void residual urine times (MD=-7.71 d, 95% CI=-8.92 to -6.50). Other bladder dysfunction symptoms, including urinary retention, nocturia, dysuria, urinary incontinence and frequent/urgent symptoms, were more likely to occur in the LRH group. Furthermore, LNSRH achieved better results in urodynamic assessments (all P<0.05). In conclusion, LNSRH was associated with lower rates of impaired bladder function and a shorter extent of resection than were observed in LRH. Clinical applications involving LNSRH should be explored with caution.

Wu, J., et al. (2019). "Laparoscopic Nerve-Sparing Radical Hysterectomy vs Laparoscopic Radical Hysterectomy in Cervical Cancer: A Systematic Review and Meta-Analysis of Clinical Efficacy and Bladder Dysfunction." Journal of Minimally Invasive Gynecology 26(3): 417.
	It is widely accepted that nerve-sparing radical hysterectomy is associated with less postoperative morbidity compared with radical hysterectomy, whereas clinical safety is similar in the 2 procedures. However, there is insufficient evidence to compare these procedures performed via a laparoscopic approach. We performed a systematic review and meta-analysis of studies to compare the clinical efficacy and the rate of bladder dysfunction, including urodynamic assessment, in laparoscopic nerve-sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH). Thirty articles including a total of 2743 participants were analyzed. Operating times were shorter (MD, 29.88 minutes; 95% confidence interval [CI], 11.92-47.83 minutes) and hospital stays were longer (MD, -1.56 days; 95% CI, -2.27 to -0.84 days) in the LRH group compared with the LNSRH group. In addition, blood loss and the number of resected lymph nodes were not significantly different between the 2 groups. However, resected parametrium length (MD, -0.02 cm; 95% CI, -0.05 to -0.00 cm) and vaginal cuff width (MD, -0.06 cm; 95% CI, -0.09 to -0.04) were smaller in the LNSRH group. Furthermore, LNSRH tended to result in more satisfactory micturition (odds ratio, 2.90; 95% CI, 2.01-4.19), shorter catheterization time (MD, -7.20 days; 95% CI, -8.10 to -6.29 days), and shorter recovery to normal postvoid residual urine time (MD, -7.71 days; 95% CI, -8.92 to -6.50 days). Other bladder dysfunction symptoms, including urinary retention, nocturia, dysuria, urinary incontinence, and frequency/urgency were more frequent in the LRH group. Furthermore, LNSRH achieved better results in urodynamic assessments (all p < .05). In conclusion, LNSRH was associated with lower rates of impaired bladder function and a shorter extent of resection compared with LRH. Clinical applications involving LNSRH should be explored with caution. (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

Wu, J. H., et al. (2021). "The effect of oral vitamin E supplementation on infertile women: A systematic review and meta-analysis." Clin. Exp. Obstet. Gynecol. 48(2): 216-222.
	
Wu, L., et al. (2022). "Efficacy and Safety of Cangfu Daotan Decoction in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis." Evidence-based complementary and alternative medicine : eCAM 2022: 4395612.
	Background: The infertility caused by polycystic ovary syndrome (PCOS) has received considerable attention. Considerable efforts have been made to improve the rates of pregnancy and live birth. Cangfu Daotan Decoction (CFDTD) is a classic prescription for treating infertility in obese women. The efficacy of CFDTD in PCOS is controversial.; Objective: To evaluate the effectiveness and safety of CFDTD in treating infertility with PCOS.; Methods: A literature search was performed in the Cochrane Library, PubMed, Embase, the China National Knowledge Infrastructure, the Wanfang Database, the VIP Chinese Biomedical science journal database, and the Chinese BioMedical database from the date of each database establishment to December 2021. Only randomized controlled trials, which were used to evaluate the efficacy of CFDTD in treating subjects with PCOS, were included in the present study. The quality of evidence was assessed using the Cochrane Reviewer Handbook 5.0.0, and meta-analysis was performed using RevMan 5.3.5 software.; Results: Fourteen studies with a total of 1,433 patients were included in this analysis. The present study indicated that CFDTD could significantly improve pregnancy rate (RR = 1.62, 95% CI (1.44, 1.83), P < 0.00001), ovulation rate (RR = 1.40, 95% CI (1.25, 1.56), P < 0.00001), and estradiol levels (SMD = 0.80, 95% CI (0.03, 1.58), P =0.04), while testosterone levels (SMD = -0.92, 95% CI (-1.52, -0.31), P =0.003), homeostatic model assessment for insulin resistance (MD = -0.56, 95% CI (-0.99, -0.12), P =0.01), total cholesterol levels (MD = -0.60, 95% CI (-0.76, -0.44), P < 0.00001), triglyceride levels (MD = -0.48, 95% CI (-0.60, -0.36), P < 0.00001), body mass index (MD = -2.96, 95% CI (-3.88, -2.03), P < 0.00001), and the incidence of adverse reactions (RR = 0.47, 95% CI (0.34, 0.65), P < 0.00001) were significantly reduced.; Conclusions: Evidence from the meta-analysis suggested that CFDTD appeared to be an effective and relatively safe treatment for PCOS. However, the influence of CFDTD on reproductive hormones, glucose metabolism, and blood lipids should be carefully concluded. Due to the low quality of the methods used in the included randomized controlled trials, further studies are required with larger sample sizes and well-designed models to confirm our findings.; Competing Interests: The authors declare that they have no conflicts of interest regarding this study. (Copyright © 2022 Linling Wu et al.)

Wu, L.-Z., et al. (2022). "[Network Meta-analysis of peroral Chinese patent medicines for activating blood and resolving stasis in treatment of endometriosis]." Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 47(11): 3073-3087.
	Network Meta-analysis was performed to systematically compare the efficacy of different Chinese patent medicines for activating blood and resolving stasis in the treatment of endometriosis and to provide evidence-based references for clinical medication regimens. The relevant randomized controlled trials(RCTs) involving Chinese patent medicines combined with conventional treatment(experimental group) vs conventional treatment(control group) were retrieved from Chinese and English literature databases. The bias risk assessment tool recommended in Cochrane handbook 5.3 was used to evaluate the quality of the included studies. The result data of each outcome index was extracted for network Meta-analysis in Stata 15.0. A total of 44 RCTs were included in this study, involving 4 345 patients and 9 Chinese patent medicines. The network Meta-analysis revealed the following trends.(1)In terms of reducing the visual analogue scale(VAS) scores, Dan'e Fukang Plaster+conventional treatment&gt;Xuefu Zhuyu Capsules+conventional treatment&gt;Gongliuxiao Capsules+conventional treatment.(2)In terms of reducing cancer antigen CA125, Xiaojin Capsules+conventional treatment&gt;Shaofu Zhuyu Granules+conventional treatment&gt;Dan'e Fukang Plaster+conventional treatment.(3)In terms of reducing estradiol(E&#95;2), Gongliuxiao Capsules+conventional treatment&gt;Xiaojin Capsules+conventional treatment&gt;Sanjie Zhentong Capsules+conventional treatment.(4) In terms of reducing recurrence rate, Guizhi Fuling Capsules+conventional treatment&gt;Xuefu Zhuyu Capsules+conventional treatment&gt;Dan'e Fukang Plaster+conventional treatment. The peroral Chinese patent medicines for activating blood and resolving stasis combined with conventional treatment have better efficacy in the treatment of endometriosis than conventional treatment. However, considering the low quality of the included literature, large-scale high-quality clinical trials are needed in the future research.

Wu, P. Y., et al. (2022). "Selenium supplementation for polycystic ovary syndrome: a meta-analysis of randomized controlled trials." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(11): 1-7.
	Introduction: The efficacy of selenium supplementation was elusive for polycystic ovary syndrome. This meta-analysis aimed to explore the efficacy of selenium supplementation for polycystic ovary syndrome. Methods: PubMed, EMbase, Web of science, EBSCO, Cochrane library database, CNKI, Chongqing VIP database and Wanfang databases have been searched through July 2022 and we included randomized controlled trials (RCTs) reporting the effect of selenium supplementation versus placebo in patients with polycystic ovary syndrome. Results: Five RCTs were included in the meta-analysis. Compared with placebo group for polycystic ovary syndrome, selenium supplementation was associated with significantly reduced total testosterone (SMD=-0.42; 95% CI=-0.78 to -0.06; p = 0.02) and cholesterol (SMD=-0.71; 95% CI=-1.41 to -0.02; p = 0.04), but revealed no remarkable influence on SHBG (SMD=-0.52; 95% CI=-1.29 to 0.25; p = 0.19), triglyceride (SMD=-1.45; 95% CI=-3.62 to 0.73; p = 0.19), LDL (SMD=-0.17; 95% CI=-0.72 to 0.37; p = 0.53), FPG (SMD=-0.95; 95% CI=-3.72 to 1.82; p = 0.50) or HOMA-IR (SMD=-0.51; 95% CI=-3.79 to 2.77; p = 0.76). Conclusions: Selenium supplementation may be able to improve the metabolic response for polycystic ovary syndrome, and this finding should be interpreted with caution.

Wu, Q., et al. (2020). "Efficacy of five-element music interventions in perinatal mental health and labor pain: A meta-analysis." Complementary Therapies in Clinical Practice 40: 101217.
	OBJECTIVE: To systematically review the efficacy of five-element music interventions in perinatal mental health and labor pain. To provide evidence for future research on Chinese Traditional Music Interventions. METHOD(S): An electronically search was conducted in Web of Science, PubMed, EMbase, The Cochrane Library, CNKI databases, WanFang Data and VIP Database for Chinese Technical Periodicals from inception to January 07, 2020 to collect randomized controlled trials (RCTs) on five-element music interventions for prenatal, perinatal and postpartum women. Literature screening, data extraction, and the risk of bias assessment of all eligible studies were conducted by two reviewers independently. Then, meta-analysis was performed by RevMan 5.3 software. RESULT(S): A total of 13 RCTs involving 2387 patients were included. The results of meta-analysis showed that five-element music could significantly improve the depression levels (SMD = -2.03, 95%CI: -2.88 to -1.19, P < 0.00001), anxiety levels (SMD = -3.49, 95%CI: -4.47 to -2.24, P < 0.00001) and severe anxiety rate (OR = 0.42, 95%CI: 0.19 to 0.94, P = 0.04) of perinatal women. Additionally, five-element music produced significant effects on labor pain (MD = -0.67, 95%CI: -0.82 to -0.52, P < 0.00001), labor duration (MD = -0.85, 95%CI: -1.07 to -0.63, P < 0.00001), the hemorrhage 2 h after parturition (MD = -19.55, 95%CI: -35.56 to -3.54, P = 0.02) and the Serum DYN expression level (MD = 1.32, 95%CI: 0.23 to 2.40, P = 0.02). CONCLUSION(S): Five-element music may be efficacious in improving perinatal women' depression, anxiety, labor pain, labor duration, the hemorrhage 2 h after parturition and the Serum DYN expression level. Because of the limitation of quantity and quality of included studies, more high-quality studies were needed to confirm the above conclusion.Copyright © 2020 Elsevier Ltd. All rights reserved.

Wu, S., et al. (2021). "Prognostic efficacy of systematic lymphadenectomy for ovarian cancer: a systematic review." Chinese Journal of Evidence-Based Medicine 21(11): 1286-1292.
	Objective To systematically review the prognostic efficacy and safety of patients with ovarian cancer treated with systemic lymphadenectomy (SL). Methods PubMed, The Cochrane Library, Web of Science, CNKI, WanFang Data, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) and cohort studies on the prognostic outcomes of patients with ovarian cancer treated with SL from inception to December 16th, 2020. Six reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 5 RCTs and 23 cohort studies involving 6 166 patients were included. The results of meta-analysis showed that there were no significant differences in the 3-year survival rate, 5-year survival rate, 3-year progression-free survival rate, and 5-year progression-free survival rate between SL group and the no systemic lymphadenectomy (NSL) group. The results of the subgroup analysis showed that pelvic and para-aortic lymph node dissection combined with large omentum resection had a better prognosis for patients. Conclusions Current evidence shows that SL has no significant efficacy on survival and progression-free survival in patients with ovarian cancer. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.Copyright © 2021 West China University of Medical Science. All rights reserved.

Wu, T., et al. (2020). "Effect of Fenugreek on vasomotor symptoms in menopausal women: A protocol for systematic review and meta-analysis." Medicine 99(23): e20526.
	Background: Vasomotor symptoms (hot flashes or night sweats) are closely related to the impaired quality of life in menopausal women. Fenugreek is the ripe seed of Trigonella foenum graecum Linn. In China, this plant is used to relieve menopausal symptoms in women. Although recent studies have shown that fenugreek may have a good effect on the menopausal symptoms, there is no meta-analysis to systematically evaluate its efficacy in improving menopausal vasomotor symptoms.; Methods: Randomized controlled trials that met the inclusion criteria will be retrieved in 5 English online databases and 4 Chinese online databases. The primary outcomes are changes in frequency and intensity of vasomotor symptoms that measured by validated scales. The secondary outcomes will include quality of life, blood hormone parameters, blood biochemical parameters, and adverse events. Heterogeneity of data will be assessed by I and Cochrane Q statistics. Sensitivity analysis and subgroup analysis will be performed to explore the sources of heterogeneity. Egger test and Begg test will be used to assess the publication bias. Finally, we will evaluate the quality of evidence by the GRADE approach. All the data statistics will be performed using the STATA 15.0 software.; Results: All the results of will be published in a peer-reviewed journal.; Conclusions: This meta-analysis will systematically evaluate the efficacy and safety of fenugreek in the treatment of menopausal vasomotor symptoms.; Osf Registration Number: 10.17605/OSF.IO/3BCY8.

Wu, X., et al. (2020). "Moxibustion for primary dysmenorrhea: Protocol for a systematic review of randomized controlled trials." Medicine 99(1): e18547.
	Background: Primary dysmenorrhea (PD) is one of the most common gynecological complaint among menstruating females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, especially, moxibustion has confirmed as an effective, convenient, and safe treatment for various types of menstrual pain. The purpose of this study is to systematically assess the effect and safety of moxibustion for treating PD.; Methods and Analysis: The following databases will be searched from their inception to December 2019: PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Wan-Fang Databases, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Citation Information by National Institute of Informatics, Chinese Scientific Journal Database. Two reviewers will search these databases, select data and evaluate the quality of studies separately. The methodological quality will be measured by the Cochrane risk of bias tool. The primary outcome is the pain degree evaluation including visual analog scale, numerical visual scale, verbal rating scale, Cox retrospective symptom scale, or any other scale used to evaluate the level of pain. And the response rate involved overall reduction in symptoms. The adverse effects, quality of life will be assessed as secondary outcomes. Risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data will be adopted to express the effect and safety of moxibustion for PD.; Trial Registration Number: PROSPERO CRD42019130141.

Wu, X., et al. (2022). "Pregnancy and Adverse Obstetric Outcomes After Hysteroscopic Resection: A Systematic Review and Meta-Analysis." Frontiers in surgery 9: 889696.
	Objective: Although the randomized controlled trial (RCT) of the efficacy of hysteroscopic resection in women with uterine septum has not shown any significant correlation in recent research, motivation for deeper study remains insufficient. In this study, the objective was to determine pregnancy-related outcomes, along with adverse obstetric outcomes, following hysteroscopic resection and also to determine whether women with hysteroscopic resection bear the same outcomes as women with normal uterine cavities.; Search Methods: From January 1995 to February 2022, a systematic literature review was conducted to identify all studies published concerning the gestation outcomes of women with and without hysteroscopic resection while comparing the gestation outcomes of women after hysteroscopic resection and with a normal uterine cavity. Our primary outcome was the live birth rate (LBR). The secondary outcomes were term delivery, preterm delivery, spontaneous miscarriage, malpresentation, cesarean section, and other adverse obstetric outcomes.; Results: 22 studies were included in this meta-analysis. The control groups of 14 studies were treated women, and the control groups of the other 8 studies were patients bearing a normal uterine cavity. Hysteroscopic resection was related to a higher rate of term delivery (OR = 2.26, 95% CI, 1.26-4.05), and a lower rate of spontaneous abortion (OR = 0.50, 95% CI, 0.27-0.93), and a lower rate of malpresentation (OR = 0.31, 95% CI, 0.19-0.50). Nevertheless, in comparison with the normal uterus group, the rates of preterm birth, cesarean section, and postpartum hemorrhage after resection did not return to normal levels.; Conclusion: Hysteroscopic resection can effectively reduce the risk of abortion and malpresentation in patients possessing a uterine septum while increasing the term delivery rate. Although well-designed RCTs should confirm our meta-analysis, it still bears recommending to patients.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Wu, Zhang, Sun, Jiang and Yan.)

Wu, Y., et al. (2019). "Autologous peripheral blood mononuclear cells intrauterine instillation to improve pregnancy outcomes after recurrent implantation failure: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 300(5): 1445-1459.
	Purpose: Recurrent implantation failure (RIF) is a common cause of disappointment and a big challenge after assisted reproduction technology treatments. The objective of this study was to evaluate the existing literature to explore whether peripheral blood mononuclear cells' (PBMCs) instillation could improve pregnancy outcomes among patients with RIF. Method(s): We conducted a comprehensive search including PubMed, EMBASE, Cochrane library and various databases in China. Three randomized controlled trials (RCTs) and three non-randomized controlled trials (non-RCTs) were included. We included subgroup and sensitivity analyses using Stata 12.0. Result(s): The results of the three RCTs showed that PBMC improved outcomes in all patients compared with placebo or no-treatment [clinical pregnancy rate (CPR): odds ratio (OR) 2.45, 95% confidence interval (CI) 1.53-3.91; implantation rate (IR): OR 2.46, 95% CI 1.48-4.09; live birth rate (LBR): OR 2.43, 95% CI 1.32-4.49]. However, the results of the three non-RCTs indicated that there were no statistically significant differences in the outcomes and that the heterogeneity was higher (I2 > 0%). Subgroup analysis further suggested that PBMCs treatment significantly increased the CPR, IR and LBR in the three or more implantation failure subgroups (CPR: OR 2.83, 95% CI 1.29-6.22; IR: OR 3.74, 95% CI 1.71-8.19; LBR: OR 3.03, 95% CI 1.15-7.98). Conclusion(s): Among patients with three or more implantation failures, this treatment improved IR, LBR, and CPR compared to that in controls, due to the limited data available, PBMCs' intrauterine instillation should only be used in the context of clinical trials.Copyright © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Wu, Y., et al. (2021). "Effects of biejiajian pills on t cell subset distribution and surface pd-1/pd-l1 expression in the treatment of endometriosis." International Journal of Clinical and Experimental Medicine 14(1): 51‐61.
	Objective: To investigate the therapeutic effect of Biejiajian pills on endometriosis and its impact on T cell subset distribution and surface PD‐1/PD‐L1 expression. Methods: A total of 98 patients with endometriosis who were admitted our hospital were divided into two groups by a random number table method, with 49 cases in each group. Patients in the control group was treated with leuprorelin acetate. Patients in the observation group was treated with Biejiajian pills in addition to the treatment of the control group. Before and after treatment, the clinical efficacy, sex hormone levels (follicle stimulating hormone, luteinizing hormone, and estradiol), tumor‐related marker levels (anti‐endometrial antibody and carbohydrate antigen 125), T cell subset levels (cluster of differentiation 4‐positive (CD4+), cluster of differentiation 8‐positive (CD8+), and the ratio of CD4+ to CD8+ T cells), expression levels of programmed death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) on the surface of CD4+ and CD8+ T cells, and the incidence of adverse reactions were compared between the two groups. Results: The total effective rate in the observation group was 95.92%, which was significantly higher than that in the control group 81.63% (P=0.025). After treatment, the CD4+ T cell count and CD4+/CD8+ ratio in the observation group were lower than those in the control group, while the CD8+ T cell count in the observation group was higher than that in the control group (P<0.05). PD‐1/PD‐L1 level on the surfaces of CD4+ and CD8+ T cells, and the levels of follicle stimulating hormone, luteinizing hormone, and estradiol in the observation group were lower than those in the control group (P<0.05). The carbohydrate antigen 125 and anti‐endometrial antibody levels in the observation group were lower than those in the control group (P<0.05). The incidences of adverse reactions in both groups were not statistically significant (P=1.000). Conclusion: Biejiajian pills as an adjunct are effective in the treatment of patients with endometriosis. They are safe, and can significantly improve the sex hormone levels, reduce tumor‐related marker levels and CD4+ T cell count, increase CD8+ T cell count, and inhibit the expression of PD‐1/PD‐L1 on the surface of T lymphocytes.

Wu, Y. e., et al. (2022). "Treatment of endometriosis with dienogest in combination with traditional Chinese medicine: A systematic review and meta-analysis." Frontiers in surgery 9: 992490.
	Background: Endometriosis is now considered to be a systemic disease rather than a disease that primarily affects the pelvis. Dienogest (DNG) has unique advantages in the treatment of endometriosis, but it also has side effects. Alternatively, Traditional Chinese Medicine (TCM) has been used for over 2000 years in the treatment and prevention of disease and growing numbers of Chinese scholars are experimenting with the combined use of Dienogest and TCM for endometriosis treatment.; Objectives: This review evaluated the efficacy and safety of TCM in combination with Dienogest in the treatment of endometriosis through meta-analysis.; Methods: MEDLINE, Embase, the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Journal Integration Platform, and Wanfang were used in literature searches, with a deadline of May 31, 2022. Literature quality was assessed using the Cochrane Collaboration "risk of bias" (ROB2) tool, and the "meta" package of R software v.4.1 was used for meta-analysis. Dichotomous variables and continuous variables were assessed using the relative risk (RR) and 95% confidence intervals (95% CI); standard mean differences (MD) and 95% CI, respectively.; Results: Twelve human randomized controlled trials (RCTs) and one retrospective study, all 13 written in the Chinese language, were included in the meta-analysis (720 experiments and 719 controls). The result indicated that TCM plus Dienogest was superior to Dienogest/TCM alone in increasing the cure rates (RR = 1.3780; 95% CI, 1.1058, 1.7172; P = 0.0043), remarkable effect rate (RR = 1.3389; 95% CI, 1.1829, 1.5154; P < 0.0001), invalid rate (RR = 0.2299; 95% CI, 0.1591, 0.3322; P < 0.0001), and rate of adverse effects (RR = 0.6177; 95% CI, 0.4288, 0.8899; P = 0.0097). The same conclusion was drawn from the subgroup analysis.; Conclusion: Results suggest that TCM combined with Dienogest is superior to Dienogest or TCM alone and can be used as a complementary treatment for endometriosis. TCMs have potential to improve clinical efficacy and reduce the side effects of Dienogest. This study was financially supported by Annual Science and Technology Steering Plan Project of Zhuzhou. PROSPERO has registered our meta-analysis as CRD42022339518 (https://www.crd.york.ac.uk/prospero/record&#95;email.php).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2022 Wu, Liu, Jia, Lou and Chen.)

Wu, Z., et al. (2020). "Which acupuncture and moxibustion technique is more effective for primary dysmenorrhea: A protocol for a network meta-analysis of randomized controlled trials." Medicine 99(35): e21713.
	Background: Primary dysmenorrhea (PD), also called functional dysmenorrhea, refers to a woman's menstrual period in genital no organic disease, abdominal pain, under the belly and other discomfort for the characteristics of disease of department of gynecology. Acupuncture and moxibustion have been accepted as treatment options for PD. So far, there are so many therapies for PD and their efficacy has been assessed by several systematic reviews. Therefore, this study aims at evaluating the effectiveness which acupuncture and moxibustion technique is more effective for primary dysmenorrhea.; Methods and Analysis: The following electronic databases will be searched in this study: the Cochrane Central Register of Controlled Trials (CENTRAL);PubMed; EMBASE; China National Knowledge Infrastructure (CNKI); Chinese Biomedical Literature Database (CBM);Chinese Scientific Journal Database (VIP database); and Wan-Fang Database(WF). More than two authors independently assessed the quality of the evidence by AMSTAR2, PRISMA, PRISMA-A, and GRADE approach. Two of our researchers will use the bias risk tool provided by the Cochrane Collaboration to evaluate the quality of the literature using WinBUGS 1.4.3 and STATA softwares. The primary outcomes include the extent of pain in the lower abdomen measured by visual analog scale (VAS) and relief from symptoms. The quality of life (QoL) and Adverse events will be considered as Additional outcome(s). Their reference lists and the citation lists of studies meeting the inclusion criteria and relevant systematic reviews will also be searched to identify further studies for inclusion. Before this review completed, the 2 reviewers will conduct the search once again to ensure the latest studies could be included.; Ethics and Dissemination: This review does not require ethical approval.; Results: The results will be published in a peer-reviewed journal.; Conclusion: This study will provide comprehensive evidence of acupuncture and moxibustion for patients with PD.; Inplasy Registration Number: INPLASY2020500106.

Wulff, V., et al. (2021). "The influence of maternal singing on well-being, postpartum depression and bonding - a randomised, controlled trial." BMC Pregnancy and Childbirth 21(1): 501.
	BACKGROUND: Postpartum depression is fairly common in new mothers and moreover associated with impaired bonding and poor maternal well-being. The aim of the present study was to investigate the impact of a mother-infant singing intervention within the first three months after birth on maternal well-being, depressive symptoms and bonding. METHODS: 120 women who were recruited at the maternity ward at the University Clinic in Düsseldorf took part in this prospective, randomised-controlled study. Beside the baseline measurement 1-3 days after childbirth, depressive symptoms, maternal well-being and mother-infant bonding were evaluated with questionnaires before (two weeks after birth) and after (twelve weeks after birth) the intervention took place. The experimental group (n = 59) participated in several singing intervention sessions while the control group (n = 61) did not. In the intervention group, salivary cortisol as well as attachment and mood were assessed immediately before and after the singing sessions. RESULTS: The participants of the intervention group showed a significant reduction of cortisol (p = .023) and an improvement of attachment and mood from start to end of the intervention session (all p ≤ .008). However, no prolonged effects were revealed beyond the intervention sessions as the two groups did not differ regarding the alterations of the primary outcomes postpartum depression (interaction effect p = .187) and postpartum bonding (interaction effect p = .188) in the 10-week period from two up to twelve weeks after childbirth (all p > .05). Additional analyses of singing habits at home in both groups, revealed that only in the singing group more frequent singing was associated with less anxiety and more well-being of the mother. CONCLUSION: Singing towards the infant seems to have positive immediate effects on the well-being of new mothers (on subjective variables as well as physiological measurements). However, the intervention did not lead to more long lasting positive effects although several limitations should be considered. TRIAL REGISTRATION: DRKS00015178 (registered at the German Clinical Trial Registry), date of registration: 09.11.2018.

Wullaert, L., et al. (2023). "Oncological surgery follow-up and quality of life: Meta-analysis." British Journal of Surgery 110(6): 655-665.
	Background: Previous trials found that more intensive postoperative surveillance schedules did not improve survival. Oncological follow-up also provides an opportunity to address psychological issues (for example anxiety, depression, and fear of recurrence). This systematic review assessed the impact of a less intensive surveillance strategy on health-related quality of life (HRQoL), emotional well-being, and patient satisfaction. Method(s): A systematic search was conducted in PubMed/MEDLINE, Embase, Web of Science, Cochrane database, PsycINFO, and Google Scholar to identify studies comparing different follow-up strategies after oncological surgery and their effect on HRQoL and patient satisfaction, published before 4 May 2022. A meta-analysis was conducted on the most relevant European Organisation for Research and Treatment of Cancer QLQ-C30 and Hospital Anxiety and Depression Scale subscales. Result(s): Thirty-five studies were identified, focusing on melanoma (4), colorectal (10), breast (7), prostate (4), upper gastrointestinal (4), gynaecological (3), lung (2), and head and neck (1) cancers. Twenty-two studies were considered to have a low risk of bias, of which 14 showed no significant difference in HRQoL between follow-up approaches. Five studies with a low risk of bias showed improved HRQoL or emotional well-being with a less intensive follow-up approach and three with an intensive approach. Meta-analysis of HRQoL outcomes revealed no negative effects for patients receiving less intensive follow-up. Conclusion(s): Low-intensity follow-up does not diminish HRQoL, emotional well-being, or patient satisfaction.Copyright © 2023 The Author(s). Published by Oxford University Press on behalf of BJS Society Ltd.

Wuytack, F., et al. (2021). "Oral non-steroidal anti-inflammatory drugs (single dose) for perineal pain in the early postpartum period." Cochrane database of systematic reviews (Online) 1(1): CD011352.
	BACKGROUND: Many women experience perineal pain after childbirth, especially after having sustained perineal trauma. Perineal pain‐management strategies are an important part of postnatal care. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are a commonly‐used type of medication in the management of postpartum pain, and their effectiveness and safety should be assessed. This is an update of a review first published in 2016. OBJECTIVES: To determine the effectiveness of a single dose of an oral NSAID for relief of acute perineal pain in the early postpartum period. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 December 2019), OpenSIGLE and ProQuest Dissertations and Theses (28 February 2020), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing a single dose of a NSAID versus a single dose of placebo, paracetamol or another NSAID for women with perineal pain in the early postpartum period. We excluded quasi‐RCTs and cross‐over trials. We included papers in abstract format only if they had sufficient information to determine that they met the review's prespecified inclusion criteria. DATA COLLECTION AND ANALYSIS: Two review authors (FW and VS) independently assessed all identified papers for inclusion and risks of bias, resolving any discrepancies through discussion. Two review authors independently conducted data extraction, including calculations of pain relief scores, and checked it for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 35 studies examining 16 different NSAIDs and involving 5136 women (none were breastfeeding). Studies were published between 1967 and 2013. Risk of bias due to random sequence generation, allocation concealment and blinding of outcome assessors was generally unclearly to poorly reported, but participants and caregivers were blinded, and outcome data were generally complete. We downgraded the certainty of evidence due to risk of bias, suspected publication bias, and imprecision for small numbers of participants. NSAID versus placebo Compared to women who receive a placebo, more women who receive a single‐dose NSAID may achieve adequate pain relief at four hours (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.64 to 2.23; 10 studies, 1573 women; low‐certainty evidence) and at six hours (RR 1.92, 95% CI 1.69 to 2.17; 17 studies, 2079 women; very low‐certainty evidence), although we are less certain about the effects at six hours. At four hours after administration, women who receive a NSAID are probably less likely to need additional analgesia compared to women who receive placebo (RR 0.39, 95% CI 0.26 to 0.58; 4 studies, 486 women; moderate‐certainty evidence) and may be less likely to need additional analgesia at six hours after initial administration, although the evidence was less certain at six hours (RR 0.32, 95% CI 0.26 to 0.40; 10 studies, 1012 women; very low‐certainty evidence). One study reported that no adverse events were observed at four hours post‐administration (90 women). There may be little or no difference in maternal adverse effects between NSAIDs and placebo at six hours post‐administration (RR 1.38, 95% CI 0.71 to 2.70; 13 studies, 1388 women; low‐certainty evidence). Fourteen maternal adverse effects were reported in the NSAID group (drowsiness (5), abdominal discomfort (2), weakness (1), dizziness (2), headache (2), moderate epigastralgia (1), not specified (1)) and eight in the placebo group (drowsiness (2), light‐headedness (1), nausea (1), backache (1), dizziness (1), epigastric pain (1), not specified (1)), although not all studies assessed adverse effects. Neonatal adverse effects were not assessed in any of the studies. NSAID versus paracetamol NSAIDs may lead to more women achieving adequate pain relief at four hours, compared with paracetamol (RR 1.54, 95% CI 1.07 to .22; 3 studies, 342 women; low‐certainty evidence). We are uncertain if there is any difference in adequate pain relief between NSAIDs and paracetamol at six hours post‐administration (RR 1.82, 95% CI 0.61 to 5.47; 2 studies, 99 women; very low‐certainty evidence) or in the need for additional analgesia at four hours (RR 0.55, 95% CI 0.27 to 1.13; 1 study, 73 women; very low‐certainty evidence). NSAIDs may reduce the risk of requiring additional analgesia at six hours compared with paracetamol (RR 0.28, 95% CI 0.12 to 0.67; 1 study, 59 women; low‐certainty evidence). One study reported that no maternal adverse effects were observed at four hours post‐administration (210 women). Six hours post‐administration, we are uncertain if there is any difference between groups in the number of maternal adverse effects (RR 0.74, 95% CI 0.27 to 2.08; 3 studies, 300 women; very low‐certainty evidence), with one case of pruritis in the NSAID group and one case of sleepiness in the paracetamol group. Neonatal adverse effects were not assessed in any of the included studies. Comparisons of different NSAIDs or doses did not demonstrate any differences in effectiveness for any primary outcome measures; however, few data were available on some NSAIDs. None of the included studies reported on any of this review's secondary outcomes. AUTHORS' CONCLUSIONS: In women who are not breastfeeding and who sustained perineal trauma, NSAIDs (compared to placebo or paracetamol) may provide greater pain relief for acute postpartum perineal pain and fewer women need additional analgesia, but uncertainty remains, as the evidence is rated as low‐ or very low‐certainty. The risk of bias was unclear for many studies, adverse effects were often not assessed and breastfeeding women were not included. While this review provides some indication of the likely effect, there is uncertainty in our conclusions. The main reasons for downgrading were the inclusion of studies at high risk of bias and inconsistency in the findings of individual studies. Future studies could examine NSAIDs' adverse effects, including neonatal effects and the compatibility of NSAIDs with breastfeeding, and could assess other secondary outcomes. Future research could consider women with and without perineal trauma, including perineal tears. High‐quality studies could be conducted to further assess the efficacy of NSAIDs versus paracetamol and the efficacy of multimodal treatments.

Wyatt Laura, C., et al. (2023). "A Culturally Adapted Breast and Cervical Cancer Screening Intervention Among Muslim Women in New York City: Results from the MARHABA Trial." Journal of cancer education : the official journal of the American Association for Cancer Education 38(2): 682-690.
	We examine the efficacy of MARHABA, a social marketing-informed, lay health worker (LHW) intervention with patient navigation (PN), to increase breast and cervical cancer screening among Muslim women in New York City. Muslim women were eligible if they were overdue for a mammogram and/or a Pap test. All participants attended a 1-h educational seminar with distribution of small media health education materials, after which randomization occurred. Women in the Education + Media + PN arm received planned follow-ups from a LHW. Women in the Education + Media arm received no further contact. A total of 428 women were randomized into the intervention (214 into each arm). Between baseline and 4-month follow-up, mammogram screening increased from 16.0 to 49.0% in the Education + Media + PN arm (p < 0.001), and from 14.7 to 44.6% in the Education + Media arm (p < 0.001). Pap test screening increased from 16.9 to 42.3% in the Education + Media + PN arm (p < 0.001) and from 17.3 to 37.1% in the Education + Media arm (p < 0.001). Cancer screening knowledge increased in both groups. Between group differences were not statistically significant for screening and knowledge outcomes. A longer follow-up period may have resulted in a greater proportion of up-to-date screenings, given that many women had not yet received their scheduled screenings. Findings suggest that the educational session and small media materials were perhaps sufficient to increase breast and cervical cancer screening among Muslim American women. ClinicalTrials.gov NCT03081507. (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Xenou, M. and K. Gourounti (2021). "Dietary Patterns and Polycystic Ovary Syndrome: a Systematic Review." Maedica 16(3): 516-521.
	Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. The goal of this study was to present the suitable diet recommended by the international literature for women with polycystic ovary syndrome to alleviate their symptoms. Methods: A systematic search of electronic databases containing medical topics was conducted. Results: A total number of 123 articles were retrieved and seven of them were relevant to our chosen topic concerning the diet-related polycystic ovary syndrome. According to research, it seems that diet plays a very important role on the clinical picture and laboratory findings of PCOS. According to the included studies, the change in the diet of women brought positive results in terms of clinical appearance of the syndrome. Ôhis review presents the type of diet that is deemed helpful in the clinical and laboratory picture of the syndrome. Conclusion: In the future, more research should be conducted on a larger population with PCOS and for a longer period of time, during which subjects would be given a specific diet. It would also be important to compare diet to mild exercise and dietary supplementation.

Xi, T., et al. (2019). "Effects of acupuncture on rates of ovulation and pregnancy in women with unruptured follicular luteinization syndrome: A protocol for systematic review and meta-analysis." Medicine 98(42): e17294.
	Background: As a fabulous part of Oriental Medcine, acupuncture and moxibustion possesses the advantage of high safety, convenience and less adverse effects. Unruptured follicular luteinization syndrome is a common cause of infertility in women of reproductive age, which seriously affects the physical and mental health of patients. Certain studies have reported that acupuncture can improve the rate of pregnancy in women with unruptured follicular luteinization syndrome. In this protocol, the effects of acupuncture on rates of ovulation and pregnancy among women with unruptured follicular luteinization syndrome will be further explored.; Methods: Electronic bibliographic databases such as: MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), Health Technology Assessment Database, and Web of Science (Science and Social Science Citation Index), PubMed, Chinese Biomedical Databaseare, Chinese VIP Information, Chinese National Knowledge Infrastructure (CNKI), all helpful to identify relevant randomized controlled trials (RCTs) of effects of acupuncture on rates of ovulation and pregnancy among women with unruptured follicular luteinization syndrome. The pooled odds ratio of achieving a clinical pregnancy, ongoing pregnancy, or live birth were used as the main outcome and the secondary outcome includes the changes of ovarian artery dynamics before and after treatment, so as to the adverse reactions of treatment. We will use RevMan 5.3 software to help us to analyze all data and use the Cochrane evaluation manual 5.1.0 to help us to assess the methodological quality for incorporated RCTs.; Result: This systematic review will provide evidence for assessing the effects of acupuncture on rates of ovulation and pregnancy in women with unruptured follicular luteinization syndrome.; Conclusion: The results of this study will be a useful reference for clinical treatment with acupuncture to improve rates of ovulation and pregnancy among women with unruptured follicular luteinization syndrome.

Xi, Y. and R. Xinyan (2024). "The effectiveness and safety of growth hormone supplementation in improving ovarian reverse function undergoing IVF or ICSI: a meta-analysis of randomized controlled trials."
	
Xia, L., et al. (2022). "Far Infrared Radiation Therapy for Gynecological Cancer-Related Lymphedema Is an Effective and Oncologically Safe Treatment: A Randomized-Controlled Trial." Lymphatic Research and Biology 20(2): 164-174.
	Background: Gynecological cancer-related lymphedema (GCRL) is a devastating condition that adversely influences function, health, and quality of life. We conducted a randomized-controlled clinical study as well as in vitro experiments to investigate the efficacy and safety of far infrared radiation (FIR) to treat lymphedema in patients having previously undergone surgery for gynecological tumors. Materials and Methods: Seventy-four women with GCRL, cancer free for 5 years or more, were randomly allocated into two treatment groups: standard of care with bandage treatment and treatment with FIR plus bandage. Variations of fluid, circumference of lymphedematous limbs, serum tumor markers (cancer antigen 125 [CA125]), inguinal-pelvic lymph nodes, vagina, lungs, and adverse reactions were assessed after 1 year. In vitro experiments examined the effects on cell viability, proliferation, apoptosis, and the cell cycle of fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells. Results: The FIR+bandage group showed significantly decreased tissue fluid and reduced limb circumference ( p < 0.05) in comparison with the control group at 1 year. There was no increase of serum CA125 in both groups, and no recurrence of neoplasia or lymphadenopathy was detected. No adverse reactions were recorded. In addition, no changes were detected after FIR treatment for fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells in cell viability, proliferation, apoptosis, and cell cycle. Conclusion: FIR can be used to treat patients with GCRL following gynecological cancer treatment. Following clinical and experimental studies, we confirm that FIR is an oncologically safe treatment for lymphedema in gynecological tumor patients.

Xia, Y., et al. (2023). "Prognostic value and adverse events of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in primary advanced and platinum-sensitive recurrent epithelial ovarian cancer: a systematic review and meta-analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 40(1): 2165729.
	Background: The original meta-analysis of hyperthermic intraperitoneal chemotherapy (HIPEC) is already outdated, owing to the latest trial results. This study aimed to clarify the efficacy and adverse events of cytoreductive surgery with HIPEC compared to conventional therapy for advanced and platinum-sensitive recurrent epithelial ovarian cancer (OC).; Methods: In this meta-analysis, phase II/III controlled trials regarding 'HIPEC' and 'ovarian cancer' were searched for in electronic databases from inception to March 2022.; Results: Twenty-one studies were included in the quantitative synthesis. The pooled hazard ratio [HR] in the HIPEC group for progression-free survival (PFS) (HR = 0.61, 95% confidence interval [CI]: 0.45-0.83, p = .002) and overall survival (OS) (HR = 0.65, 95% CI: 0.51-0.82, p < .001) were improved in the HIPEC group compared with the non-HIPEC group. For primary advanced disease, OS and PFS were significantly increased in patients receiving interval debulking surgery + HIPEC, whereas PFS was not significantly different between primary debulking surgery (PDS) + HIPEC and PDS alone. For platinum-sensitive recurrent disease, no correlation was observed for PFS and OS between the HIPEC and non-HIPEC groups ( p < .05). The incidence of procedure-related complications was higher in the HIPEC group than in the non-HIPEC group (odds ratio = 1.93, 95% CI: 1.24-3.01, p < .01). The morbidity of leukopenia, neutropenia, nausea, hypoalbuminemia, and grades III-IV electrolyte disturbance was higher in the HIPEC group than in the non-HIPEC group. However, HIPEC administration reduced the risk of intra-abdominal bleeding and constipation.; Conclusion: HIPEC-based regimens improved the clinical prognosis for primary advanced OC, whereas no significant value was elicited for recurrent OC.

Xia, Y., et al. (2021). "Efficacy of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with polycystic ovary syndrome: a systematic review and meta-analysis." Annals of Palliative Medicine 10(6): 6425-6437.
	Background: There is a close relationship between cardiovascular risk factors and polycystic ovary syndrome (PCOS), and omega-3 fatty acids may have a key role in improving cardiovascular risk factors. We conducted the current systematic review and meta-analysis to evaluate the effect of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with PCOS.; Methods: We searched 4 databases including PubMed (MEDLINE), Cochrane Library, Embase, and Web of Science from inception to February 2021. We included randomized controlled trials (RCTs) that reported the effects of omega-3 fatty acid treatment for PCOS. According to the Cochrane system evaluation guide manual, 2 researchers independently assessed the methodological quality of the included studies. We pooled results using either a fixed effect model or random effect model.; Results: We identified 314 articles, of which 10 met the criteria for inclusion, involving 778 participants. The pooled results suggested an association between the supplementation of omega-3 fatty acids and a reduction in serum insulin [-2.58 pmol/L, 95% confidence interval (CI): -3.34 to -1.82 pmol/L, P<0.00001, I2=0], homeostatic model assessment of insulin resistance (HOMA-IR) (-0.57, 95% CI: -0.75 to -0.40 L, P<0.00001, I2=2%), serum total cholesterol (TC) (-6.87 mg/dL, 95% CI: -10.28 to -3.47 mg/dL, P<0.0001, I2=95%), serum triglyceride (-4.03 mg/dL, 95% CI: -5.53 to -2.52 mg/dL, P<0.00001, I2=97%), serum low-density lipoprotein cholesterol (LDL-C) (-6.64 mg/dL, 95% CI: -11.58 to -1.70 mg/dL, P=0.008, I2=99%), serum very low-density lipoprotein cholesterol (VLDL-C) (-3.29 mg/L, 95% CI: -6.54 to -0.05 mg/L, P=0.05, I2=72%), serum high-sensitivity C-reactive protein (hs-CRP) (-8.97mg/dL, 95% CI: -17.66 to -0.28 mg/dL, P=0.04, I2=99%), an improvement in serum high-density lipoprotein cholesterol (HDL-C) (2.94 mg/dL, 95% CI: 0.63 to 5.26 mg/dL, P=0.01, I2=87%), but no effect on serum glucose (-0.76 mg/dL, 95% CI: -1.71 to 0.19 mg/dL, P=0.12, I2=73%) was found.; Discussion: The current meta-analysis demonstrated that omega-3 fatty acid supplementation for women with PCOS resulted in a statistical improvement in insulin, HOMA-IR, TC, triglyceride, LDL-C, VLDL-C, and HDL-C, but did not affect serum glucose. The limitation of this paper is due to the lack of included research literature.

Xianfeng, X. and W. Xiaohan (2022). "The effectiveness of motherwort injection in preventing post-abortion hemorrhage after induced abortion: a protocol for systematic review and meta-analysis."
	
Xiang, L., et al. (2024). "Efficacy of metformin combined with vitamin D in the treatment of polycystic ovarian syndrome: A meta-analysis." African journal of reproductive health 28(2): 43-54.
	Polycystic ovary syndrome (PCOS), as an endocrine and metabolic disorder, affects approximately 6% -20% of women of childbearing age. This study aims to assess the therapeutic effects of Metformin combined with vitamin D in PCOS patients. Eight databases were searched to obtain randomized controlled trials, both domestically and internationally, on the effects of Metformin combined with vitamin D in patients with PCOS. Data analysis was performed using RevMan 5.3 software. Nine studies were ultimately included in this meta-analysis. Six studies reported the homeostatic model assessment for insulin resistance of the test group and the control group, which was significantly lower (SMD: -0.23; 95% Cl: -0.42,-0.04; P<0.05) than the control group, body mass index (BMI) (SMD: -1.86; 95% Cl: -2.77,-0.96; P<0.01), Serum 25 (OH) D (SMD: 14.28; 95% Cl: 12.26,16.29; P<0.01), testosterone (SMD: -0.11; 95% Cl: -0.15,-0.07; P<0.01) and regulated menstrual cycles (OR: 1.27; 95% Cl: 0.99,1.63; P=0.063). Our meta-analysis of nine trials demonstrates significant reductions in insulin resistance, BMI, and testosterone levels, along with increased serum vitamin D levels and improved menstrual cycle regulation after Metformin and vitamin D treatment. These findings suggest the potential of this combined therapy in managing the multifaceted aspects of PCOS.Copyright African Journal of Reproductive Health © 2024.

xianghui, z. and W. fang (2021). "Effect of subcutaneous injection granulocyte colony stimulating factor (G-CSF) for falure women under assisted reproductive technology : a meta analysis."
	
Xianyang, H., et al. (2023). "Cyclosporine A for Recurrent Spontaneous Abortion: A Meta-Analysis and Comprehensive Systematic Review Incorporating Chinese and English Literature."
	
xiao, m., et al. (2022). "Curative Effect of Adjuvant Chemotherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials."
	
Xiao, M., et al. (2021). "Efficacy and safety of Chinese herbal footbaths for the treatment of dysmenorrhea: Protocol for a systematic review and meta-analysis." PloS One 16(5): e0250685.
	Background: Chinese herbal footbaths are an external therapy of traditional Chinese medicine that has been widely used to treat dysmenorrhea. This review aims to systematically evaluate its efficacy and safety for the treatment of dysmenorrhea.; Methods: Databases of PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Database (VIP), Wanfang Database, China Biomedical Literature Database(CBM), and Chinese Biomedical Literature Service System (SinoMed) will be searched from the inception to September 30, 2020. The eligible randomized controlled trials (RCTs) will be identified and included. The primary outcomes include pain intensity measured by validated scales of visual analog scale, numeric rating scale, and response rate of symptom reduction. The secondary outcomes are scores on validated pain questionnaires, quality of life measured by SF-36 or other validated scales, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted by two reviewers independently. RevMan software (V.5.3.5) will be utilized to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of the evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System.; Results: A high-quality synthesis of current evidence of Chinese herbal footbaths for patients with dysmenorrhea will be provided in this study.; Conclusion: This systematic review will provide evidence of whether Chinese herbal footbaths are an effective and safe intervention for the treatment of dysmenorrhea.; Systematic Review Registration: PROSPERO CRD42020188256.; Competing Interests: The authors have declared that no competing interests exist.

Xiao, P., et al. (2022). "Effect of Light Therapy on Cancer-Related Fatigue: A Systematic Review and Meta-Analysis." Journal of pain and symptom management 63(2): e188-e202.
	Context: Light therapy is a non-pharmacological therapy that is currently being studied in cancer-related symptoms and is certificated as a low-risk intervention by FDA. Cancer-related fatigue (CRF) is the most common symptom reported by cancer patients.; Objective: To examine the effectiveness of light therapy for CRF in cancer patients through a systematic review and meta-analysis.; Methods: We conducted a systematic review of four electronic databases targeted randomized clinical trials evaluating light therapy for CRF (CRD42020215446), from inception to May 2021. The primary outcome was changes of CRF scores; secondary outcomes included depression, sleep, and quality of life (QoL). We quantitatively pooled outcomes using meta-analysis with random-effects models and assessed methodological bias.; Results: We identified thirteen RCTs representing 551 cancer patients, encompassing breast (n = 5), ovarian or endometrial (n = 1), multiple myeloma (n = 1), lung (n = 1), or combined (n = 5) cancers. The comparison groups included dim light (n = 12) and waiting list (n = 1). Duration of intervention ranged from 1 to 12 weeks. Light intensities ranged from 417.9 to 12,000 lux. Light therapy was associated with a significant improvement in CRF (SMD = 0.45, P = 0.007), depression (SMD = -0.26, P = 0.03) and sleep difficulty (SMD = -2.46, P = 0.0006); a statistically non-significant trend was observed for QoL (SMD = 0.33, P = 0.09). Funnel plots for CRF suggest not significant publication bias.; Conclusion: Light therapy could be a feasible and effective option for improving CRF in cancer patients. Larger sample, rigor trials design and a standard protocol of intervention are needed to draw more conclusive conclusions. (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Xiao, W., et al. (2019). "Metaanalysis of effect of pelvic floor muscle training during pregnancy to prevent or treat urinary incontinence in primipara." Chinese Nursing Research 33(1): 29-36.
	OBJECTIVE: To conduct a meta-analysis of the effectiveness of pelvic floor muscle training (PFMT) in the prevention or treatment of urinary incontinence (UI) in primiparous during pregnancy. METHODS: Literatures on clinical randomized controlled trials (RCTs) of prevention or treatment of UI in primiparous using PFMT and conventional care during pregnancy were retrieved from the China Biology Medicine (CBM), VIP database, China National Knowledge Infrastructure (CNKI), WanFang database, Pubmed, EB- sco, and Web of Science. After reviewing the bias risk of inclusion studies, RevMan 5. 3 software was used for meta-analysis. RESULTS: A total of 4 954 patients were enrolled including 14 articles. Results of the meta-analysis showed PFMT during pregnancy could effectively intervene the occurrence of UI in primipara, while the further subgroup analysis showed that the effect of the intervention on PFMT during pregnancy was different for a different groups of cases. Primipara without antenatal UI (prevention) who had PFMT were less likely to report UI in late pregnancy and 3 months after delivery [late pregnancy RR=0.17, 95%CI(0.03, 0.95), P=0.04];3 months after delivery [i?R = 0.52, 95%CI (0.38, 0.70), P<0.000 1]. While the result of meta-analysis failed to support the effectiveness of PFMT (treatment) on reducing UI(P>0.05) for primipara with antenatal UI. For a mixed population (women with and without antenatal UI symptoms), PFMT could prevent and treat UI in late pregnancy, 0-3 months after delivery and 3-6 months after delivery UI[late pregnancyRR = 0.78, 95%CI(0.71, 0.85), P<0.000 01 ;0-3 months after delivery RR=0.67, 95%CK0.55, 0.80), P<0.0001; 3 -6months after delivery RR = 0.66, 95%CI(O. 52, 0.84), P = 0.000 8]. CONCLUSIONS: Antenatal PFMT had certain effects to prevent and treat UI in late pregnancy and 3 months after delivery for primipara without antenatal UI and the mixed population. While there were not enough evidences to prove that antenatal PFMT could treat UI for primipara with antenatal UI. In the future, high-quality, especially large-sample, multi-center randomized controlled trials will be needed to increase the strength of the argument.

Xiao-dan, L. and L. Li-na (2022). "The effect of Aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion: a systematic review and meta-analysis."
	
Xiaoman, D., et al. (2023). "Acupuncture Combined with Pelvic Floor Rehabilitation Training for Postpartum Stress Urinary Incontinence: A Systematic Review and Meta-Analysis." PROSPERO International prospective register of systematic reviews.
	
Xiaoqian, L., et al. (2021). "Aspirin for polycystic ovarian syndrome: a meta-analysis and systematic review."
	
Xie, B., et al. (2023). "Assessing the impact of transplant site on ovarian tissue transplantation: a single-arm meta-analysis." Reproductive biology and endocrinology : RB&E 21(1): 120.
	Background: Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered.; Objective: This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes.; Methods: We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English.; Results: Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I 2 : 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I 2 : 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I 2 : 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I 2 : 0.00%, fixed effect).; Conclusion: Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation.; Registration Number: INPLASY202390008. (© 2023. The Author(s).)

Xie, C., et al. (2020). "Mindfulness-based stress reduction can alleviate cancer- related fatigue: A meta-analysis." Journal of Psychosomatic Research 130: 109916.
	Objectives: The purpose of this meta-analysis was to critically evaluate the effects of mindfulness-based stress reduction (MBSR) on cancer-related fatigue (CRF). Method(s): A systematic search of eight databases (Web of Science, Pubmed, Cochrane Library, Spring link, CNKI, Wanfang, VIP, CBM) was performed, to find randomized controlled trials (RCTs) from inception to January 2019. Using Cochrane Collaboration criteria, two reviewers critically and independently assessed the risk of bias and extracted correlated data using the designed form. All analyses were performed with Review Manager 5.3. Result(s): In all, fifteen RCTs were included in the systematic review, fourteen of which, consisting of 3008 patients (MBSR, 1502; control, 1506), were included in the meta-analysis. MBSR had a significant effect on fatigue in cancer patients, particularly among lung cancer patients. The meta-analysis also indicated that MBSR could significantly mitigate CRF compared with usual care or no intervention. 8 weeks of MBSR, supervised by experts, had a large effect on CRF. Conclusion(s): MBSR is effective for CRF management and can be recommended as a beneficial complementary therapy for CRF patients.Copyright © 2019

Xie, C., et al. (2019). "Effect of XPC polymorphisms on the response to platinum-based chemotherapy: A meta-analysis." OncoTargets and therapy 12: 3839-3848.
	Objective: As an important DNA repair gene, the xeroderma pigmentosum complementation group C (XPC) gene and its functional genetic variants' relationship with chemotherapy response has been extensively studied. To quantitatively elucidate the genetic impact of the XPC rs2228000 and rs2228001 polymorphisms on the response to platinum-based chemotherapy, the present meta-analysis was conducted. Material(s) and Method(s): A systematic literature search was performed in seven cyber databases until February 20, 2019, for all relevant studies that assessed the relationship between XPC polymorphisms and the response to platinum-based chemotherapy. Odds ratios (ORs) with a 95% confidence interval (95% CI) were measured to assess the strength of the association. R programs were developed to perform the statistical analyses, including calculations of pooled estimates, publication bias and sensitivity analyses, and heterogeneity interpretations. Result(s): A total of 1,615 patients from 10 studies for the rs2228001 polymorphism were winnowed for further statistical analysis. For the rs2228000 polymorphism, 858 samples from six datasets were included. However, this meta-analysis indicated no significant effect of these two XPC polymorphisms on the response to platinum-based chemotherapy. When stratified according to sample size, country or cancer type, no statistical significance for association was identified in all subgroups. Further sensitivity analysis and publication bias assessment ensured the reliability of the meta-analysis. Conclusion(s): The pooled estimates suggest that neither the rs2228000 polymorphism nor the rs2228001 polymorphism contributes to the genetic predisposition for an altered response to platinum-based chemotherapy. Considering the limitations of our present meta-analysis, more studies with large-scale cohorts and rigorous methods are needed to validate our results.Copyright © 2019 Xie et al.

Xie, H., et al. (2024). "Potential therapeutic effects of Chinese herbal medicine in postpartum depression: Mechanisms and future directions." Journal of Ethnopharmacology 324: 117785.
	Ethnopharmacological Relevance: Postpartum depression (PPD) is a common psychiatric disorder in women after childbirth. Per data from epidemiologic studies, PPD affects about 5%-26.32% of postpartum mothers worldwide. Biological factors underlying this condition are multiple and complex and have received extensive inquiries for the roles they play in PPD. Chinese herbal medicine (CHM), which is widely used as a complementary and alternative therapy for neurological disorders, possesses multi-component, multi-target, multi-access, and low side effect therapeutic characteristics. CHM has already shown efficacy in the treatment of PPD, and a lot more research exploring the mechanisms of its potential therapeutic effects is being conducted.; Aim of the Review: This review provides an in-depth and comprehensive overview of the underlying mechanisms of PPD, as well as samples the progress made in researching the potential role of CHM in treating the disorder.; Materials and Methods: Literature was searched comprehensively in scholarly electronic databases, including PubMed, Web of Science, Scopus, CNKI and WanFang DATA, using the search terms "postpartum depression", "genetic", "hormone", "immune", "neuroinflammation", "inflammation", "neurotransmitter", "neurogenesis", "brain-gut axis", "traditional Chinese medicine", "Chinese herbal medicine", "herb", and an assorted combination of these terms.; Results: PPD is closely associated with genetics, as well as with the hormones, immune inflammatory, and neurotransmitter systems, neurogenesis, and gut microbes, and these biological factors often interact and work together to cause PPD. For example, inflammatory factors could suppress the production of the neurotransmitter serotonin by inducing the regulation of tryptophan-kynurenine in the direction of neurotoxicity. Many CHM constituents improve anxiety- and depression-like behaviors by interfering with the above-mentioned mechanisms and have shown decent efficacy clinically against PPD. For example, Shen-Qi-Jie-Yu-Fang invigorates the neuroendocrine system by boosting the hormone levels of hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes, regulating the imbalance of Treg/T-helper cells (Th) 17 and Th1/Th2, and modulating neurotransmitter system to play antidepressant roles. The Shenguiren Mixture interferes with the extracellular signal-regulated kinase (ERK) pathway to enhance the number, morphology and apoptosis of neurons in the hippocampus of PPD rats. Other herbal extracts and active ingredients of CHM, such as Paeoniflorin, hypericin, timosaponin B-III and more, also manage depression by remedying the neuroendocrine system and reducing neuroinflammation.; Conclusions: The pathogenesis of PPD is complex and diverse, with the main pathogenesis not clear. Still, CHM constituents, like Shen-Qi-Jie-Yu-Fang, the Shenguiren Mixture, Paeoniflorin, hypericin and other Chinese Medicinal Formulae, active monomers and Crude extracts, treats PPD through multifaceted interventions. Therefore, developing more CHM components for the treatment of PPD is an essential step forward.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.)

Xie, H., et al. (2019). "Effect of intrauterine perfusion of human chorionic gonadotropin before embryo transfer after two or more implantation failures: A systematic review and meta-analysis." European Journal of Obstetrics and Gynecology and Reproductive Biology 243: 133-138.
	Objective: To investigate whether intrauterine perfusion of hCG before embryo transfer (ET) is effective in women experienced two or more implantation failures. Study design: Systematic review and meta-analysis. In the current meta-analysis, Pubmed, EMBASE and The Cochrane Library were searched for trials which compared the efficacy of intrauterine perfusion of hCG with no perfusion of hCG in women undergoing in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or frozen embryo transfer (FET) before ET. The primary outcomes are the clinical pregnancy rate (CPR) and live birth rate (LBR). Result(s): Six trials consisted of 1432 women were eligible for quantitative analysis. CPR (including 6 trials consisted of 1432 women) and LBR (including 3 trials consisted of 870 women) were significantly improved in the hCG group compared to the control group, with a CPR of 41.8 % vs. 31.2 % (RR 1.30, 95 % CI 1.14~1.50, P < .001), an LBR of 27.8 % vs. 18.0 % (RR 1.52, 95 % CI 1.18~1.96, P = .001). Conclusion(s): Intrauterine perfusion of hCG is effective in improving clinical pregnancy rate and live birth rate in women who experienced two or more implantation failures, which might provide a potential therapeutical intervention for recurrent implantation failure (RIF). Although promising, further evidence from multicenter, randomized controlled trials are needed to confirm the conclusion from the current meta-analysis.Copyright © 2019 Elsevier B.V.

Xie, H., et al. (2023). "Chinese herbal medicine for threatened miscarriage: An updated systematic review and meta-analysis." Frontiers in Pharmacology 14: 1083746.
	Objective: To conduct an updated systematic review and meta-analysis on the efficacy and safety of Chinese herbal medicine (CHM) for threatened miscarriage. Data Sources: Electronic databases were searched from inception to 30 June 2022. Study Eligibility Criteria: Only randomized controlled trials (RCTs) that assessed the efficacy and safety of CHM or combined CHM and Western medicine (CHM-WM) and compared with other treatments for threatened miscarriage were included for analysis. Methods: Three review authors independently evaluated included studies, assessed the risk of bias and extracted data for meta-analysis (continuation of pregnancy after 28 gestational weeks, continuation of pregnancy after treatment, preterm birth, adverse maternal outcomes, neonatal death, TCM syndrome severity, β-hCG levels after treatment), sensitivity analysis (β-hCG level) and subgroup analysis (TCM syndrome severity, β-hCG level). The risk ratio and 95% confidence interval were calculated by RevMan. Certainty of the evidence was assessed according to GRADE. Results: Overall, 57 RCTs involving 5,881 patients met the inclusion criteria. Compared with WM alone, CHM alone showed significant higher incidence of continuation of pregnancy after 28 gestational weeks (Risk Ratio (RR) 1.11; 95% CI 1.02 to 1.21; n = 1; moderate quality of evidence), continuation of pregnancy after treatment (RR 1.30; 95% CI 1.21 to 1.38; n = 10; moderate quality of evidence), higher β-hCG level (Standardized Mean Difference (SMD) 6.88; 95% CI 1.74 to 12.03; n = 4) and lower Traditional Chinese medicine (TCM) syndrome severity (SMD -2.94; 95% CI -4.27 to -1.61; n = 2). Compared with WM alone, combined CHM-WM showed significant higher incidence of continuation of pregnancy after 28 gestational weeks (RR 1.21; 95% CI 1.16 to 1.27; n = 15; moderate quality of evidence), continuation of pregnancy after treatment (RR 1.19; 95% CI 1.16 to 1.23; n = 41; moderate quality of evidence), higher β-hCG level (SMD 2.27; 95% CI 1.72 to 2.83; n = 37) and lower TCM syndrome severity (SMD -1.74; 95% CI -2.21 to -1.27; n = 15). No significant differences in reducing the adverse maternal outcomes and neonatal death were found in combined CHM-WM compared with WM alone (RR 0.97; 95% CI 0.62 to 1.52; n = 8; RR 0.39; 95% CI 0.12 to 1.21; n = 2). Conclusion: Current evidence supported CHM could be a potential treatment for threatened miscarriage. However, results should be interpreted with caution considering the low to moderate quality of the available evidence. Systematic Review Registration: [https://inplasy.com/inplasy-2022-6-0107/], identifier [INPLASY20220107].; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Xie, Zhang, Mou, He, Li, Wang, Fan and Li.)

Xie, L., et al. (2020). "Chinese herbal medicine for assisted reproduction technology: A protocol for a systematic review and meta-analysis." Medicine 99(37): e22009.
	BACKGROUND: Human assisted reproductive technology (ART) has become an important part of infertility treatments throughout the world, including IVF, ICSI, embryo culture, and embryo cryopreservation. In China and East Asia, Chinese herbal medicine (CHM) has been used to treat various diseases and improves the success chance of live birth among infertile couples undergoing ART treatment. The aim of this study is to assess the effect and safety of Chinese herbal medicine among women undergoing ART. METHODS: Cochrane Library, MEDLINE, EMBASE, CNKI, VIP, CBM and WANGFANG will be searched. All randomized controlled trials will be included if they recruited participants undergoing ART for assessing the effect and safety of Chinese herbal medicine. Primary outcomes will be live birth. Two authors will independently scan all the potential articles, extract the data and assess the risk of bias using Cochrane tool of risk of bias. Based on the guideline of Cochrane Collaboration, all analysis will be performed by RevMan 5.3 software. Dichotomous variables will be expressed as RR with 95% CIs and continuous variables will be reported as MD with 95% CIs. If possible, a fixed or random effects models will be conducted and the confidence of cumulative evidence will be assess using GRADE. RESULTS: This study will be to assess the effect and safety of Chinese herbal medicine among women undergoing ART. CONCLUSIONS: This study will assess the effect and safety of Chinese herbal medicine among women undergoing ART and move forward to help inform clinical decisions.

Xie, L., et al. (2019). "The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials." Evidence-based complementary and alternative medicine : eCAM 2019: 7918631.
	Purpose: To assess the efficacy and safety of berberine on reproductive endocrine and metabolic outcomes in women with polycystic ovary syndrome (PCOS).; Methods: PubMed (from 1950), the Cochrane Library, the CNKI (from 1979), the VIP (from 1989), and the Wanfang Data (from 1990) and the reference lists of the retrieved articles were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome/PCOS" and "berberine/BBR/Huangliansu (in Chinese)/Xiao bojian (in Chinese)" till 30 May 2019. Relevant indicators were collected and the data were analyzed by using RevMan 5.3 software.; Results: Eventually, a total of 12 randomized controlled trials were included in this systematic review. Our study suggested that berberine had similar live birth rates compared with placebo or metformin and lower live birth rates (RR: 0.61, 95% CI: 0.44 to 0.82) compared with letrozole. There was a significant difference between berberine and placebo and between berberine and no treatment in terms of decreasing total testosterone and luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio (8 RCTs, 577 participants, MD: -0.34, 95% CI: -0.47 to -0.20; 3 RCTs, 179 participants, MD: -0.44, 95% CI: -0.68 to -0.21, respectively). Berberine was associated with decreasing total cholesterol (3 RCTs, 201 participants; MD: -0.44, 95% CI: -0.60 to -0.29), waist circumference (3 RCTs, 197 participants, MD: -2.74, 95% CI: -4.55 to -0.93), and waist-to-hip ratio (4 RCTs, 258 participants, MD: -0.04, 95% CI: -0.05 to -0.03) compared with metformin, but not with improved BMI (4 RCTs, 262 participants, MD: -0.03, 95% CI: -0.46 to 0.39). Berberine did not increase the incidence of gastrointestinal adverse events (3 RCTs, 567 participants, RR: 1.01, 95% CI: 0.76 to 1.35) or serious events during pregnancy (RR: 0.98, 95% CI: 0.70 to 1.37) compared with placebo.; Conclusion: This review found no solid evidence that berberine could improve live birth or other clinical outcomes in women with PCOS. However, berberine appeared to be more efficacious for improving insulin resistance and dyslipidemia and decreasing androgen levels and LH/FSH ratio in women with PCOS when compared with metformin.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2019 Liangzhen Xie et al.)

Xie, N., et al. (2021). "A systematic review comparing early with late removal of indwelling urinary catheters after pelvic organ prolapse surgery." International Urogynecology Journal 32(6): 1361-1372.
	Background: An indwelling catheter is routinely used after pelvic organ prolapse surgery to prevent urinary retention. However, the timing of catheter removal remains controversial.; Objectives: To investigate the optimal timing of catheter removal following prolapse surgery.; Methods: Electronic databases including the Cochrane Center Controlled Test Center, Embase, CINAHL, MEDLINE, PubMed, Web of Science and CNKI were searched up to January 2010. Randomized controlled trials (RCTs) comparing different timings of catheter removal after prolapse surgery were eligible. Results from RCTs comparing early versus late removal were pooled, and different durations of catheterization were divided into three sub-comparisons (≤ 2 days versus > 2 days; ≤ 1 day versus 2 days; < 1 day versus 1 day). Primary outcomes were urinary tract infection (UTI) and re-catheterization. Secondary outcomes were the length of hospital stay and patient-reported outcomes.; Results: Seven RCTs with 964 women were involved in the analysis. Early catheter removal was associated with a reduced incidence of UTI (RR 0.46, 95% CI 0.24 to 0.9) but an increased risk of re-catheterization (RR 2.67, 95% CI 1.6 to 4.48). Significant differences in primary outcomes were found in the sub-comparison of ≤ 2 days versus > 2 days. Three of six trials found a significantly shorter length of hospital stay in the early removal group. The results for postoperative pain were mixed.; Conclusion: Among patients following pelvic organ prolapse surgery, early catheter removal is preferred. Moreover, the timing for removal is preferably within 2 days postoperatively.

Xie, Q., et al. (2024). "Impact of haemostasis methods during ovarian cystectomy on ovarian reserve: a pairwise and network meta-analysis." Journal of Obstetrics and Gynaecology 44(1): 2320294.
	Background: Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known. Method(s): The Cochrane Library, PubMed and Web of Science databases were searched from the date of inception of the database to June 2022 for literature exploring the impact of haemostasis methods during ovarian cystectomy on ovarian reserve. A traditional meta-analysis was performed using Review Manager software. A network meta-analysis (NMA) was performed using Stata and GemTC software. Result(s): The direct meta-analysis comparison indicated that the mean postoperative reduction of anti-Mullerian hormone (AMH) level was significantly higher in the electrocoagulation (bipolar) group than suture and haemostatic sealant group, both in the overall group and subgroup of women with ovarian endometrioma. In NMA, the reduction of postoperative AMH levels in the electrocoagulation (bipolar) group was higher than the suture group at 6 months with a statistical significance, and at 1, 3 and 12 months without a significant difference. The difference in the postoperative decrease of AMH level did not reach statistical significance between suture and sealant, coagulation and haemostatic sealant. The comprehensive ranking results revealed that suture treatment was, with the highest probability, beneficial to the protection of the ovarian reserve. Conclusion(s): There was insufficient research to detect the optimal haemostasis method for ovarian reserve preservation in ovarian cystectomy. Nevertheless, haemostasis by electrocoagulation (bipolar) should be avoided when possible, and the suture might be considered as the best choice.Copyright © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Xie, Y., et al. (2020). "Efficacy and safety of Buzhong Yiqi decoction combined with surgery for rectal prolapse: A protocol for systematic review and meta analysis." Medicine 99(41): e22732.
	Background: It is extremely easy for rectal prolapse to relapse with surgery alone. Clinical practice indicates that Buzhong Yiqi decoction combined with surgery has certain therapeutic advantages, while there is a lack of evidence-based medicine support. This study aimed to systematically investigate the efficacy and safety of Buzhong Yiqi decoction combined with surgery in the treatment of rectal prolapse.; Methods: The English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructure [CNKI], Wanfang, China Science and Technology Journal Database [VIP], China Biology Medicine disc) were searched by computer. In addition, Baidu Scholar and Google Scholar were searched manually. A randomized controlled clinical study of Buzhong Yiqi decoction combined with surgery in the treatment of rectal prolapse was performed from the establishment of databases to September 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature.; Results: The efficacy and safety of Buzhong Yiqi decoction combined with surgery in the treatment of rectal prolapse were evaluated in terms of efficiency, symptom score, recurrence rate, adverse reaction rate, and so on.; Conclusions: Thisstudy provides reliable evidence-based support for the clinical application of Buzhong Yiqi decoction combined with surgery in the treatment of rectal prolapse.; Osf Registration Number: DOI: 10.17605/OSF.IO/K3PJX.

XiHeng, D., et al. (2023). "High Mediterranean diet adherence favors assisted reproductive technology outcomes&#xff1a;A meta-analysis."
	
Xin, C., et al. (2022). "Acupuncture combined with metformin increases pregnancy rate in patients with polycystic ovary syndrome: a systematic review and meta-analysis." PROSPERO International prospective register of systematic reviews.
	
Xin, C., et al. (2022). "Effect of Exercise on Vascular Function and Blood Lipids in Postmenopausal Women: A Systematic Review and Network Meta-Analysis." International Journal of Environmental Research and Public Health 19(19).
	This study aimed to compare and rank the effectiveness of aerobic exercise (AE), resistance training (RT), combined training (CT), and water exercise (WE) on vascular function and blood lipids in postmenopausal women using a network meta-analysis (NMA).; Methods: We searched the PubMed, Cochrane, Embase, Web of Science, and EBSCO (SPORTDiscus) databases to identify randomized controlled trials investigating the effects of exercise on vascular function and blood lipids in postmenopausal women. The retrieval period was from inception to March 2022. Two reviewers independently screened the retrieved articles, extracted pertinent data, and assessed the risk of bias of the included studies.; Results: A total of 38 studies involving 1407 patients were included in this study. The results of the NMA indicated that WE had the greatest effect on systolic blood pressure (SBP) (surface under the cumulative ranking [SUCRA] = 84.9) and total cholesterol (TC) (SUCRA = 93.1); CT had the greatest effect on triglycerides (TG) (SUCRA = 96.2), high-density lipoprotein cholesterol (HDL-C) (SUCRA = 94.8), and diastolic blood pressure (DBP) (SUCRA = 91.1); RT had the greatest effect on low-density lipoprotein cholesterol (LDL-C) (SUCRA = 79.4).; Conclusion: The results suggest that exercise can effectively improve the PWV, SBP, and DBP and the levels of TC, TG, and LDL-C in postmenopausal women. WE had the best effect on improving TC and SBP. CT had the best effect on improving TG, HDL-C, and DBP. To improve LDL-C, RT can achieve a good effect. Considering the limitations of NMA, more RCTS need to be performed in the future to provide more direct evidence of the effectiveness of various exercise interventions on vascular health in postmenopausal women.

Xing, C., et al. (2020). "Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women with PCOS." Journal of Clinical Endocrinology and Metabolism 105(9): 2950-2963.
	Objective: To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS). Method(s): We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method. Result(s): Fourteen trials reporting on 619 women were included. Compared with metformin, metformin + thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin + glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD -2.53; 95% CrI, -3.96 to -1.09), both metformin + GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin + TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone-binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin + GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD -1.77; 95% CrI, -3.25 to -0.29), lower androstenedione (WMD -2.70; 95% CrI, -3.91 to -1.50) and lower fasting blood glucose (WMD -0.41; 95% CrI, -0.73 to -0.08). Conclusion(s): For overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.Copyright © Endocrine Society 2020.

Xing, W., et al. (2023). "Effects of acupoint application therapy combined with chinese herbal medicine on perimenopausal syndrome: A systematic review and meta-analysis of randomized controlled trails." Complementary Therapies in Medicine 72: 102916.
	Background: An increasing number of women suffer from perimenopausal syndrome (PMS) and the global burden of this disease has been steadily rising. Acupoint application therapy and Chinese herbal medicine (CHM) are widely used as effective methods for treating PMS, but the efficacy was inconsistent and the evidence should be summarized by quantitively analysis.; Objective: The purpose of this systematic review and meta-analysis was to evaluate the clinical efficacy and safety of the acupoint application combined with the CHM for the treatment of PMS.; Methods: We searched eight databases from their inception to August 2022 to identify relevant studies. Only randomized controlled trials (RCTs) focusing on acupoint application combined with CHM for the treatment of PMS were included in this study. To assess the clinical efficacy and safety, meta-analysis was used to quantitively synthesize the effect estimates. Subgroup analysis, publication bias assessment and sensitivity analysis were also performed. We further assessed whether the included studies had reported on the purity and potency of the CHM used in their trials.; Results: A total of 8 RCTs with 560 participants were included in the systematic review and meta-analysis, of which none of them included a description of an independent testing of purity or potency of the CHM product used. There were significant differences between the acupoint application combined with CHM and CHM alone in terms of Kupperman Menopausal Index (KMI) score (MD = -2.91, 95%CI: -3.91 to -1.91), total effective rate (RR = 1.22, 95% CI: 1.11-1.34), Pittsburgh Sleep Quality Interview (PSQI) score (MD = -2.86, 95% CI: -3.61 to -2.10) and reduction in the serum level of luteinizing hormone (LH) (MD = -2.52, 95% CI: -4.70 to -0.34), whereas there were no differences between the two groups regarding lowering serum level of follicle-stimulating hormone (FSH) (MD = -1.66, 95% CI: -3.98-0.67) and elevating serum level of oestradiol (E 2 ) (MD = 2.41, 95% CI: -0.70-5.52). For the comparation between the acupoint application combined with CHM and western medicine (WM), the KMI score (MD = -6.80, 95%CI: -7.95 to -5.65) was substantially different, while the PSQI score (MD = -0.60, 95% CI: -1.88-0.68) was not substantially different. The total effective rate in the combined group (91.7%) was higher than the western medicine group (83.49%).; Conclusion: Acupoint application combined with CHM may enhance the efficacy and safety of patients with PMS. However, due to the lack of description of an independent testing of purity or potency of the CHM product used in the trials, as well as blinding of participants and investigators, these results should be interpreted with caution.; Competing Interests: Conflict of interest statement No potential conflict of interest was reported by the authors. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Xinhua, C. and W. Cong (2022). "Effect of Low Frequency Electro-acupuncture on Glucose and Lipid Metabolism in PCOS Women."
	
Xinyu, X., et al. (2022). "Motherwort Injection for Preventing Uterine Hemorrhage in Women With Induced Abortion: A Systematic Review and Meta-Analysis of Randomized Evidence." Frontiers in Pharmacology 13: 916665.
	Objective: Motherwort injection (MI) is a modern patented injection extracted from motherwort (Leonurus japonicus Hoult). Empirical studies and systematic reviews have shown the benefits of motherwort injection for preventing postpartum hemorrhage after vaginal delivery and cesarean section. This study was conducted to explore the efficacy and safety of motherwort injection for women with the prevention of post-abortion uterine hemorrhage. Methods: A comprehensive literature search was conducted to identify RCTs regarding the effect of the use of motherwort injection in women after abortion. Data from trials were pooled by meta-analysis and a random-effects model was used to calculate the summarized relative risks (RRs) and their 95% confidence intervals (CIs). The grading of recommendations assessment, development, and evaluation (GRADE) methodology was used to access the quality of the evidence. Results: Nine trials with a total of 1,675 participants were identified. Overall, motherwort injection combined with oxytocin compared to oxytocin had a significantly lower blood loss within 2 hours (MD = -50.00, 95% CI -62.92 to -37.08, very low quality); lower blood loss within 24 h (MD = -50.00, 95% CI -62.92 to -37.08, very low quality); however, there was no significant difference between motherwort injection and oxytocin (24 h: MD: 0.72, 95% CI -7.76 to 9.20; 48 h: MD: -0.01, 95% CI -11.35 to 11.33; 72 h: MD: -1.12, 95% CI -14.39 to 12.15, very low quality). Compared with oxytocin or no intervention, both motherwort injection and motherwort injection combined with oxytocin had a significantly decreased duration of blood loss (MI vs. O: MD -2.59, 95% CI -4.59 to -0.60, very low quality; MI + O vs. O: MD -2.62, 95% CI -3.02 to -2.22, very low quality; MI + O vs. No intervention: MD: -1.80, 95% CI -2.28 to -1.33, low quality). Seven of nine included trials reported adverse event outcomes. Three cases were found in the motherwort injection group, and five induced abortion syndromes were found in the motherwort injection plus oxytocin group. 29 adverse events were reported in the oxytocin group instead. The recovery time of normal menstruation after abortion was significantly earlier in the group using motherwort injection compared with oxytocin (MDs -3.77, 95% CI -6.29 to -1.25, very low quality), and the endometrial thickness in the motherwort injection group was significantly different from that in the oxytocin group (MD: 2.24, 95% CI 1.58 to 2.90, very low quality). Conclusion: The results of this meta-analysis indicate prophylactic use of motherwort injection may reduce the risk of uterine hemorrhage in women after abortion, and more high-quality research is needed to confirm the efficacy and safety of motherwort injection in preventing uterine hemorrhage after abortion. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=274153, identifier CRD42021274153.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Xinyu, Xintong, Youping, Feng and Jiajie.)

xinyue, f. and L. Yan (2023). "A meta-analysis of the effectiveness of aerobic combined resistance in patients with ovarian cancer."
	
Xiong, R.-G., et al. (2022). "Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review." Molecules (Basel, Switzerland) 27(14).
	Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial activities. In addition, berberine shows anticancer effects on a variety of cancers, such as breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. The underlying mechanisms of action include inhibiting cancer cell proliferation, suppressing metastasis, inducing apoptosis, activating autophagy, regulating gut microbiota, and improving the effects of anticancer drugs. This paper summarizes effectiveness and mechanisms of berberine on different cancers and highlights the mechanisms of action. In addition, the nanotechnologies to improve bioavailability of berberine are included. Moreover, the side effects of berberine are also discussed. This paper is helpful for the prevention and treatment of cancers using berberine.

Xiu-Mei, F., et al. (2021). "Efficacy and Safety of Gabapentin for Chronic Pelvic Pain in Women: A Systematic Review and Meta-analysis of Randomized Controlled Trials." PROSPERO International prospective register of systematic reviews.
	
Xiuping, Z., et al. (2023). "Impact of endometriosis on female sexual function and interventions in improving outcomes: A systematic review and meta-analysis."
	
Xi-wen, L. I., et al. (2021). "Effect of Bushen Huoxue Decoction on endometriosis infertility&#xff1a;systematic review and meta analysis."
	
Xi-wen, L. I., et al. (2021). "Traditional Chinese Medicine for recurrence rate in patients with endometriosis treated by conservative operation : a systematic review and meta-analysis."
	
Xixuan, Y. U. and W. U. Yue (2022). "Effect of granulocyte colony-stimulating factor on pregnancy outcomes in women with recurrent miscarriage: a meta-analysis."
	
Xu, D., et al. (2020). "Intradermal acupuncture for primary dysmenorrhea: A protocol of systematic review and meta-analysis of randomized clinical trials." Medicine 99(37): e22188.
	Background: Primary dysmenorrhea (PD) is one of the common gynecological diseases, the incidence of PD is on the rise and young women are more likely to have it, which seriously affects women's physical, mental health and work life. Intradermal acupuncture is effective in treating PD. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on intradermal acupuncture and provide effective evidence for further research.; Methods: We will search the following electronic databases from their inception to July 2020: Electronic database includes PubMed, Embase, Cochrane Library, Chinese Biomedical Database WangFang, VIP medicine information, and CNKI (China National Knowledge Infrastructure). Primary outcomes: the overall effective rate, VAS score.; Secondary Outcomes: blood serum estradiol (E2), progesterone (P), prostaglandin F2α (PGF-2α), adverse events Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0.; Results: The results of this study will systematically evaluate the effectiveness and safety of intradermal acupuncture in the treatment of primary dysmenorrhea.; Conclusion: The systematic review of this study will summarize the currently published evidence of intradermal acupuncture therapy for primary dysmenorrhea to further guide its promotion and application.

Xu, D., et al. (2020). "The role systematic lymphadenectomy plays in determining the survival outcome for advanced ovarian cancer patients: a meta-analysis." Annals of Palliative Medicine 9(3): 912-920.
	Background: This study aims to evaluate the role systematic lymphadenectomy (SL) p l a y s in advanced ovarian cancer (OC) patients. A meta-analysis was done to compare the progression-free survival (PFS) rates and overall survival (OS) rates between SL and unsystematic lymphadenectomy (USL).; Methods: An extensive literature search from the dates of January 1, 1994, to today was performed. In total, we analyzed 15 studies [3 randomized controlled trials (RCTs) and 12 observation studies], which included 33,257 patients with advanced OC who underwent SL or USL. We compared the survival outcomes of PFS and OS between SL and USL stratified by research type, respectively. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were combined and analyzed by using the Revman 5.3 software.; Results: For RCTs, SL did not improve the survival outcomes for advanced OC. Only 2 RCTs compared PFS, and 3 RCTs compared the OS rates between SL and USL. Two RCTs demonstrated that there was no difference in PFS between SL and USL (HR: 0.91; 95% CI: 0.81-1.04; P=0.16>0.05); at the same time, 3 RCTs also demonstrated that there were no difference in OS between SL and USL (HR: 0.94, 95% CI: 0.88-1.00; P=0.07>0.05). However, in observational studies, SL showed increased PFS (HR: 0.93, 95% CI: 0.92-0.95; P<0.00001) and OS (HR: 0.91, 95% CI: 0.89-0.93, P<0.00001) for advanced OC patients. The heterogeneity and publication bias in the included studies were within acceptable thresholds.; Conclusions: These findings suggest the possibility that SL cannot improve survival outcomes for advanced OC patients. However, we cann ot completely ignore the results of observational studies. More relevant RCTs are needed to investigate the role of SL for advanced OC patients.

Xu, F., et al. (2021). "The comparison of myomectomy, UAE and MRgFUS in the treatment of uterine fibroids: a meta analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 38(2): 24-29.
	Objective: To compare the re-intervention rates of myomectomy, uterine artery embolization (UAE) and magnetic resonance-guided focused ultrasound surgery (MRgFUS) for uterine fibroids (UFs) in different follow-up time.; Methods: Two investigators searched PubMed for clinical studies published in English from 1 Jan 2000 to 31 Dec 2020, and independently examined the paper to select qualified studies, extracted relevant information and assessed the risk of bias. Meanwhile, a meta-analysis of 31 studies containing totally 42103 patients was conducted to compare the re-intervention rate of myomectomy, UAE and MRgFUS.; Results: In the meta-analysis of 42103 patients, the 12-month re-intervention rates of myomectomy, UAE and MRgFUS for UFs were 0.06 (95%CI, 0.01-0.11), 0.07 (95%CI, 0.06-0.09), and 0.12 (95%CI, 0.04-0.20) respectively. The 24-month re-intervention rates were 0.10 (95%CI, 0.04-0.16), 0.08 (95%CI, 0.01-0.17), and 0.14 (95%CI, 0.07-0.21) respectively. The 36-month re-intervention rates were 0.09 (95%CI, 0.05-0.13), 0.14 (95%CI, 0.05-0.23), and 0.22 (95%CI, 0.11-0.32) respectively. Additionally, the 60-month re-intervention rates were 0.19 (95%CI, 0.15-0.24), 0.21 (95%CI, 0.17-0.25), and 0.49 (95%CI, 0.21-0.77) respectively.; Conclusions: The myomectomy has the lowest re-intervention rate of the three regimens in short time and long time while the MRgFUS has the highest. The rate of MRgFUS increased rapidly in the 60th month after the treatment.

Xu, H., et al. (2023). "Meta-analysis of the efficacy of laparoscopic uterosacral ligament suspension in patients with pelvic organ prolapse." Journal of Gynecology Obstetrics and Human Reproduction 52(10): 102634.
	Objective: This study aimed to evaluate the efficacy of laparoscopic uterosacral ligament suspension (LUSLS) for pelvic organ prolapse (POP) using a meta-analysis method.; Methods: All articles about LUSLS published in English from Jan. 2010 to Jan. 2020 were retrieved using a computer from search engines, including PubMed, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and Chinese Medical Journals. Meta-analysis was performed by two evaluators using RevMan 5.3 software according to the inclusion criteria.; Results: A total of five studies were finally included, with 361 LUSLS cases and 361 control cases. LUSLS group showed a shorter operation duration (SMD-1.96; 95% CI = -3.90- -0.03; P = 0.05), more POP-quantification system (Q) (I) (SMD1.64; 95% CI = 1.05-2.56; P = 0.03), than the control group, with significant differences. There was no difference in the complication incidence, hospital stay, POP-Q>=II between the 2 groups (P > 0.05).; Conclusion: LUSLS was a safe and effective treatment for POP. Patients had higher postoperative satisfaction, shorter operation duration and satisfactory outcome. More high-quality randomized controlled trials are required in the future to make the results of the meta-analysis more accurate.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Masson SAS.)

Xu, H., et al. (2021). "Effect of acupuncture for diminished ovarian reserve: study protocol for a randomized controlled trial." Trials 22(1): 720.
	Background: Diminished ovarian reserve (DOR) is a condition in which the ovary loses its normal reproductive potential, compromising fertility. Although the prevalence and incidence of DOR is increasing, there are currently no effective treatments for this condition. Acupuncture has been reported as an alternative therapy for female infertility. The purpose of this study is to investigate the effect of acupuncture for women with DOR.; Methods/design: In this randomized controlled trial, a total of 120 women with DOR will be randomly assigned to receive either acupuncture or sham acupuncture for 12 weeks. The primary outcome will be determined by the mean change from baseline in the antral follicle count (AFC) at week 12. Secondary outcomes include serum levels of FSH, LH, E2, and AMH, the length of menstrual cycle, and the score of Self-Rating Anxiety Scale (SAS).; Discussion: This study is expected to investigate the effectiveness of acupuncture versus sham acupuncture in improving ovarian reserve for women with DOR.; Trial Registration: Acupuncture-Moxibustion Clinical Trial Registry ChiCTR1800014988 . Registered on 6 February 2018. (© 2021. The Author(s).)

Xu, H., et al. (2023). "Effectiveness of aerobic exercise in the prevention and treatment of postpartum depression: Meta-analysis and network meta-analysis." PloS One 18(11): e0287650.
	Background: Aerobic exercise is widely recognized for improving mental health and reducing negative emotions, including anxiety. However, research on its role in preventing and treating postpartum depression (PPD) has yielded inconsistent results. Some studies show positive effects on PPD symptoms, while others find limited impact, suggesting various factors at play, such as exercise type, intensity, and individual differences. To address this gap, our study aims to comprehensively gather evidence on the preventive and therapeutic effects of aerobic exercise for PPD. We'll focus on differences in exercise program design and implementation, exploring how these factors impact intervention outcomes. By identifying effective exercise approaches, we aim to provide more comprehensive exercise prescription recommendations for this vulnerable population.; Methods: We conducted a quantitative systematic review of the study in 5 representative databases for the effect of aerobic exercise on PPD. Meta-analysis and network meta-analysis were performed with Review-Manager.5.4 and Stata.16.0 software, respectively. This study has been registered on the official Prospero website, and the registration code is CRD42023398221.; Results: Twenty-six studies with 2,867 participants were eventually included and the efficacy of aerobic exercise in preventing and treating postpartum depression is significant compared to standard care. (MD = -1.90; 95%CL: -2.58 to -1.21; I2 = 86%). Subgroup analysis suggests that the intervention objective (prevention vs. treatment) of exercise could potentially be a source of heterogeneity in this study, as the "Test for subgroup difference" revealed the presence of significant distinctions (p = 0.02<0.05). The "Test for subgroup difference" yielded non-significant results for both the supervised vs. unsupervised subgroup comparison (p = 0.55 > 0.05) and the individual vs. team subgroup comparison (p = 0.78 > 0.05). Nonetheless, when assessing their effect sizes [Subtotal (95%CL)], the supervised exercise group [-1.66 (-2.48, -0.85)] exhibited a slightly better performance than the unsupervised exercise group [-1.37 (-1.86, -0.88)], while the team exercise group [-1.43 (-1.94, -0.93)] slightly outperformed the individual exercise group [-1.28 (-2.23, -0.33)]. Network meta-analysis indicated that moderate intensity (35~45 min) group demonstrated a more pronounced intervention effect compared to low intensity (50~60 min) group [-2.63 (-4.05, -1.21)] and high intensity (20~30 min) group [-2.96 (-4.51, -1.41)], while the 3~4 times/week group had a more significant intervention effect compared to 1~2 times/week groups [-2.91 (-3.99, -1.83)] and 5~6 times/week groups [-3.28 (-4.75, -1.81)]. No significant differences were observed in pairwise comparisons of intervention effects among the five common types of aerobic exercises. (95%CL including 0). The Surface Under the Cumulative Ranking curve (SUCRA) results align with the findings mentioned above and will not be reiterated here.; Conclusion: The efficacy of aerobic exercise in preventing and treating postpartum depression is significant compared to standard care, with a greater emphasis on prevention. The optimal prescribed exercise volume for intervention comprises a frequency of 3~4 exercise sessions per week, moderate intensity (35~45 minutes). Currently, several uncharted internal factors influence the optimal intervention effect of aerobic exercise, such as the potential enhancement brought by team-based and supervised exercise. Given the absence of significant differences in certain results and the limitations of the study, it is essential to exercise caution when interpreting the outcomes. Further research is needed in the future to provide a more comprehensive understanding.; Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction i any medium, provided the original author and source are credited.)

Xu, H., et al. (2023). "Meta-analysis of the efficacy and safety of Xihuang Pills/capsules in adjuvant treatment of uterine cervical neoplasms." Medicine 102(34): e34846.
	Background: Xihuang Pills/Capsules have a longstanding history of utilization in traditional Chinese medicine (TCM) for treating cancer. Nevertheless, a comprehensive investigation is required regarding the specific impacts and safety of Xihuang Pills/Capsules in individuals with uterine cervical neoplasms. Thus, conducting a meta-analysis is essential to evaluate the clinical effectiveness of combining Xihuang Pills/Capsules with Western medicine in patients with cervical neoplasms.; Methods: The research involved searching 5 English and 4 Chinese databases for randomized controlled trials (RCTs) investigating the use of Xihuang Pills/Capsules in conjunction with Western medicine for treating uterine cervical neoplasms. Subsequently, statistical analysis was carried out using Review Manager software (version 5.3).; Results: This research encompassed 10 RCTs involving 937 patients. The findings revealed that the combination of Xihuang Pills/Capsules with Western medicine treatment led to improvements in various aspects of the patients' condition. Specifically, there was an enhancement in the short-term efficacy rate (risk ratio [RR] = 1.14, 95% confidence interval [CI]: 1.06-1.22, P = .0003), Karnofsky performance score (KPS) (mean difference [MD] = 5.90, 95% CI: 0.54-11.26, P = .03), survival rates, CD3+, CD3 + CD4+, CD3 + CD8+, CD3-CD56 + cells, and immunoglobulin M in patients with uterine cervical neoplasms. Moreover, the combination treatment resulted in a reduction of adverse reactions, including gastrointestinal reactions (RR = 0.52, 95% CI: 0.42-0.64, P < .00001), radiation proctitis (RR = 0.47, 95% CI: 0.33-0.68, P < .0001), myelosuppression (RR = 0.41, 95% CI: 0.26-0.64, P < .0001), as well as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) levels. Additionally, the treatment exhibited an inhibitory effect on white blood cells (WBCs) and platelets (PLTs).; Conclusion: The amalgamation of Xihuang Pills/Capsules with conventional anti-tumor therapy proves to be both effective and safe in the treatment of cervical neoplasms. However, further validation through high-quality RCTs is necessary to substantiate these findings.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Xu Hong, W., et al. (2019). "Effectiveness and safety of warm needle acupuncture on insomnia in climacteric women: Protocol for a systematic review and meta-analysis." Medicine 98(20): e15637.
	Background: Warm needle acupuncture (WNA) is a traditional Chinese medicine (TCM) therapy which combines technical advantages of acupuncture and moxibustion. Climacteric insomnia is a common symptom in climacteric women, which can seriously affect the physical and mental health of patients. Relevant studies have been reported that WNA can improve insomnia in climacteric women. In this protocol, the effectiveness and safety of WNA on insomnia in climacteric women will be explored.; Methods: Seven electronic databases include 3 English databases [Excerpta Medica database (EMBASE), PubMed, the Cochrane Central Register of Controlled Trials (Cochrane Library)] and 4 Chinese databases [Chinese VIP Information, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang Database] for randomised controlled trials (RCT) of WNA on insomnia in climacteric women will be searched. The changes of the Pittsburgh sleep quality index was used as the main outcome, and the secondary outcome includes the changes of the Kupperman score, serum hormone level, and TCM syndrome score, as well as the adverse events caused by WNA. We will use RevMan software V5.3 to help us to analyze all data and use a Cochrane risk of bias tool to help us to assess the methodological quality for RCTs.; Result: This study will provide reliable evidence for WNA on insomnia in climacteric women CONCLUSION:: The findings will be an available reference to evaluate the effectiveness and safety of WNA on insomnia in climacteric women.; Registration: PROS-PERO CRD42019125743.

Xu, J., et al. (2022). "Effectiveness of self-myofascial release combined with biofeedback and electrical stimulation for the management of myofascial pelvic pain: A randomized controlled trial." European journal of pain (London, England) 26(2): 405-416.
	Background: Myofascial pelvic pain (MFPP) caused by myofascial trigger points (MTrPs) is a major contributor to chronic pelvic pain in women. However, the effect of the patient's self-myofascial release (SMFR) is unclear. This study aimed to investigate the effect of SMFR combined with biofeedback and electrical stimulation (BES) therapy in comparison with BES alone in patients with MFPP.; Methods: A prospective randomized controlled study was conducted. Sixty-eight patients were randomly allocated into BES-SMFR group (n = 34) and BES group (n = 34). Every patient received 4 weeks of treatment, evaluated at baseline (T0), 4 weeks post-intervention (T4) and 12-week follow-up (T12). The primary outcome was pain intensity. The secondary outcomes were degree of activation of MTrPs, surface electromyography (sEMG) levels and Patient Global Impression of Improvement (PGI-I).; Results: Compared with the effect of BES, BES-SMFR treatment significantly decreased pain intensity and the degree of activation of MTrPs in the levator ani (p = 0.02) and obturator internus (p = 0.03), as well as the sEMG levels of the pre-test resting baseline and post-test resting baseline (all p < 0.01). The degree of activation of MTrPs in the piriformis and coccygeus (all p > 0.05) and the sEMG levels of the quick flicks and endurance contraction were not significantly different. The BES-SMFR treatment improved the PGI-I scale at T4 (p = 0.02) but not at T12 (p = 0.40).; Conclusions: This study confirmed that the addition of SMFR to BES treatment resulted in superior outcomes compared with those with BES alone in patients with MFPP.; Significance Statement: Myofascial pelvic pain (MFPP) is a major contributor of female chronic pelvic pain. Myofascial release has been used commonly for better pain release; however, poor therapeutic effect due to poor patient compliance is common in clinical practice. Therefore, in future research, there is a need to investigate the effect of patient's self-myofascial release (SMFR) technique, which can eliminate the need for frequent office visits and improve patient compliance to some extent, in patients with MFPP. (© 2021 European Pain Federation - EFIC®.)

Xu, K., et al. (2023). "The efficacy and toxicity of mirvetuximab soravtansine, a novel antibody-drug conjugate, in the treatment of advanced or recurrent ovarian cancer: a meta-analysis." Expert review of clinical pharmacology 16(11): 1141-1152.
	Introduction: This meta-analysis aims to systematically analyze the efficacy and toxicity of mirvetuximab soravtansine (MIRV) as second-line and above treatment for advanced or recurrent ovarian cancer.; Methods: Candidate studies were identified in PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases up to 1 May 2023. Objective response rate (ORR), progression-free survival (PFS), the incidence of adverse events (AEs), and incidence of grade ≥ 3 AEs were extracted and calculated by meta-analysis of merging ratios or mean to describe the efficacy and toxicity of MIRV.; Results: Seven eligible prospective studies were included in this meta-analysis, including 605 patients with advanced ovarian cancer who received second-line or higher therapy. ORR of MIRV was 34.2% (95% confidence interval [CI] 25.0-43.5), and PFS was 5.82 months (95%CI 4.47-7.18). The overall incidence of AEs was 87.4% (95%CI 52.9-100.0) and the incidence of grade ≥ 3 AEs was 27.1% (95%CI 18.9-36.1). The most common AEs were vision blurring, nausea, and diarrhea, with incidence of 46.7% (39.6-53.8), 41.8% (34.0-49.9), and 41.3% (30.4-52.5), respectively.; Conclusions: MIRV has definite efficacy and good safety as a novel choice for second-line and above treatment of advanced or recurrent FRα positive ovarian cancer. This may have promising application in patients with platinum-resistant diseases.; Prospero Registration Number: CRD42023428599.

Xu, L., et al. (2023). "Comparison on radiofrequency ablation and laparoscopic myomectomy for treating symptomatic uterine fibroids: Meta-analysis." Chinese Journal of Interventional Imaging and Therapy 20(11): 664-669.
	Objective To compare the efficacy of radiofrequency ablationRFAand laparoscopic myomectomyLMfor treating symptomatic uterine fibroids using meta-analysis. Methods Literature about RFA and LM for treating symptomatic uterine fibroids were searched in PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine discCBMdisc,CNKI,VIP databases and Wanfang Med Online from the establishment of database to August 31, 2022, and the relevant data were extracted. Review Manager 5. 3 was used for analysis, and the efficacy of treating symptomatic uterine fibroids were compared between RFA and LM. Results Totally 11 articles were enrolled,including 994 patients with symptomatic uterine fibroids,497 cases in RFA group and 497 cases in LM group. Compared with those in LM group, the intraoperative bleeding volume, hospital stay, operation time, postoperative recovery time to normal activities, as well as postoperative pregnancy rate were all lower in RFA groupOR= - 19. 87, - 1. 71, - 1. 85,-6. 31, 0. 57, all P0. 05, while no significant difference of the incidence of postoperative complication was found between groupsP>0. 05. Conclusion Compared with LM, RFA had advantages such as shorter operation time and hospital stay, lower intraoperative bleeding volume and faster recovery of normal postoperative activities for treating symptomatic uterine fibroids,but the impact of RFA on postoperative pregnancy rate was more obvious than LM.Copyright © 2023 Editorial Office - Chinese Journal of Interventional Imaging and Therapy. All rights reserved.

Xu, L., et al. (2019). "The Effect of Dehydroepiandrosterone (DHEA) Supplementation on IVF or ICSI: A Meta-Analysis of Randomized Controlled Trials." Geburtshilfe und Frauenheilkunde 79(7): 705-712.
	Introduction A systematic review and meta-analysis were conducted to evaluate the efficacy of dehydroepiandrosterone (DHEA) supplementation in patients with diminished ovarian reserve (DOR) and/or poor ovarian response (POR) who were undergoing in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI). Patients and Methods We searched the PubMed, EMBASE, Web of Science, and Cochrane Library electronic databases for literature published until July 2018. The analysis included randomized controlled trials (RCTs) of the effects of DHEA versus placebo on IVF or ICSI. Two independent reviewers extracted information from the reports and evaluated the quality of the studies. Overall, we identified nine prospective RCTs involving 833 patients. Results Compared to the controls, patients treated with DHEA exhibited increases in the number of retrieved oocytes (mean difference, 0.91; 95% confidence interval [CI], 0.23 - 1.59; p = 0.009), clinical pregnancy rate (relative risk [RR] = 1.27; 95% CI, 1.01 - 1.61; p = 0.04), and live birth rate (RR, 1.76; 95% CI, 1.17 - 2.63; p = 0.006). However, there was no intergroup difference in the miscarriage rate (RR, 0.37; 95% CI, 0.12 - 1.13; p = 0.08). Conclusion DHEA supplementation improved the outcomes of IVF/ICSI in women with DOR or POR.

Xu, L., et al. (2023). "Zishen yutai pill as an adjuvant therapy in threatened Miscarriage:A meta-analysis of 23 randomized controlled trials." Heliyon 9(6): e16213.
	Objective: The purpose of this study was to evaluate the efficacy and safety of Zishen Yutai Pill combined with western medicine for the treatment of women with threatened miscarriage during the first trimester of pregnancy.; Methods: Randomized controlled trials published before the end of Apr 1, 2023 on Zishen Yutai Pill and threatened miscarriage were systematically retrieved from China National Knowledge Infrastructure, Wanfang, Sinomed, VIP, PubMed, EMBASE, Web of Science and the Cochrane Library. The international clinical trial registration platform and the Chinese clinical trial registration platform of clinical trials was searched from their inception until Apr 1, 2023. Meta analysis of random effect model was used to combine the research data. Chi-squared test and I 2 statistics were used for heterogeneity test.; Results: Twenty-three trials (enrolling 2411 participants) were included in the review. Zishen Yutai pill combined with western medicine therapy showed significant improvement on human chorionic gonadotropin [MD 19.33 IU/ml, 95% CI (15.84, 22.81)], the total effective rate [RR 1.19, 95% CI (1.15-1.23)], progesterone [MD 7.14 ng/ml, 95% CI (6.14, 8.13)], estradiol [MD 33.69 pg/ml, 95% CI (27.42, 39.96)], duration of abdominal pain [MD -2.36 d, 95% CI (- 3.54, - 1.18)], duration of vaginal bleeding [MD -1.94 d, 95% CI (- 2.93, - 0.94)], and fibrinogen [MD -0.34 g/L, 95% CI (- 0.57, - 0.11)]. There was no significant difference in hematocrit [MD 0.68%, 95% CI (- 0.08, 1.44)] between the experimental and the control group. Zishen Yutai Pill may improve the clinical symptoms in women with threatened miscarriage, such as human chorionic gonadotropin the total effective rate, progesterone, estradiol, duration of abdominal pain, duration of vaginal bleeding, and fibrinogen. Especially for progesterone, the effect of treatment ≦2 weeks is significantly better than treatment of >2 weeks. For estradiol, the effect of treatment >2 weeks is significantly better than treatment of ≦ 2 weeks.; Conclusion: Zishen Yutai Pill, as a complementary therapy, significantly improved human chorionic gonadotropin, the total effective rate, progesterone, estradiol, abdominal pain, vaginal bleeding, and fibrinogen in patients with threatened miscarriage in first-trimester pregnancy. However, the systematic review has some limitations, such as degraded information quality, no blinding of patients or doctors, etc. Due to the small sample size and low quality of research, it needs to be further confirmed by large sample and high-quality randomized controlled trials, such as blinding of patients, doctors and outcome assessment should be complemented, clinical follow-up, live birth rate, fetal growth should be supplemented.; Systematic Review Registration: INPLASY202320039.; Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper (© 2023 The Authors. Published by Elsevier Ltd.)

Xu, L., et al. (2019). "Effect of Chinese herbal medicine on primary dysmenorrhea: A protocol for a systematic review and meta-analysis." Medicine 98(38): e17191.
	Background: Primary dysmenorrhea (PD), the most common gynecological diseases, seriously affects women's life and work; however, without more effective treatment. Chinese herbal medicine (CHM) has been widely used for relieving dysmenorrheic pain in patients with PD. To assess the effectiveness and safety of CHM in patients with PD, a systematic review and meta-analysis of current published evidence regarding CHM as treatment for PD would be conducted in this study.; Methods: Literatures related to CHM for PD from the establishment of the database to June 2019 will be retrieved from the following databases: MEDLINE, EMBACE, Wed of Science and Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database. There are no language restrictions for retrieving literature. Eligible randomized clinical trials (RCTs) evaluating the effectiveness and safety of CHM in PD patients will be put in the study including outcomes of pain intensity, clinical effectiveness rate, quality of life, and adverse events. By scanning the titles, abstracts and full texts, 2 reviewers will independently select studies, extract data, and assess the quality of study. Meta-analysis of RCTs will be conducted using Review Manager 5.1 software. The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data.; Result: This study will provide high-quality available evidence for the treatment of PD with CHM based on pain, clinical efficacy, quality of life, and adverse events.; Conclusion: The systematic review willto evaluate the efficacy of CHM in treating PD and provide evidence for clinicians.; Prospero Registration Number: CRD42019121185.

Xu, S., et al. (2023). "Evidence-based complementary and alternative medicine conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility: A systematic review and meta-analysis." PloS One 18(5 May): e0285859.
	Background Chinese medicinal retention enemas have gradually attracted the attention of clinicians as an alternative approach for tubal obstructive infertility. The purpose of this study was to investigate the efficacy and safety of conventional surgery combined with traditional Chinese medicinal retention enemas for the treatment of tubal obstructive infertility. Materials and methods Eight electronic databases were searched from their inception to November 30, 2022. To assess the efficacy and safety of different treatments, following outcomes were measured: clinical pregnancy rate, clinical total effective rate, incidence of ectopic pregnancy, the improvement of Traditional Chinese Medicinal (TCM) symptoms, the improvement of the signs of obstructive tubal infertility and side effects. Results A total of 23 Randomized Controlled Trials (RCTs) with 1909 patients met the inclusion criteria. The pooled results showed a higher pregnancy rate in the experimental group than in the control group (RR 1.75, 95% CI [1.58, 1.94], Z = 10.55, P<0.00001). The clinical total effective rate in the experimental group was higher than that in the control group (RR 1.28, 95% CI [1.23, 1.34], Z = 11.07, P<0.00001). The incidence of ectopic pregnancy in the experimental group was lower than that in the control group (RR 0.40, 95% CI [0.20, 0.77], Z = -2.73, P = 0.01). Conclusion Based on current evidence, we concluded that conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility was superior to conventional surgery alone in improving the clinical pregnancy rate, improving clinical total effective rate, improving TCM symptoms, improving the signs of obstructive tubal infertility and lowering the incidence of ectopic pregnancy. However, further clinical trials with high-quality methodologies need to be conducted.Copyright © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Xu, S. M., et al. (2022). "Efficacy Evaluation of Dingkundan in Treatment of Female Infertility: A Systematic Review Based on Randomized Controlled Trials." Chinese Journal of Experimental Traditional Medical Formulae 28(8): 239-247.
	This study systematically evaluated the effectiveness and safety of Ding kundan combined with conventional western medicine in the treatment of female infertility. Four Chinese databases, three English databases, and two clinical trial registration platforms were retrieved from inception to April 2021. Two researchers independently carried out literature screening, data extraction, risk assessment of bias, and grading of evidence quality. Rev Man 5.4.1 was used for data analysis. A total of 216 research articles were retrieved and 21 randomized controlled trials (RCTs) were included, involving 2 172 cases. The risks of bias in the included RCTs were high. As unraveled by Meta-analysis results, Ding kundan combined with western medicine for ovulation stimulation was superior to western medicine for ovulation stimulation alone in improving pregnancy rate and progesterone level [relative risk(RR)pregnancy rate=1.67, 95% confidence interval(CI)(1.44, 1.93); standardized mean difference(SMD)progesterone=1.21, 95% CI(0.82, 1.60). Ding kundan combined with western medicine for improving the endometrium was superior to western medicine for improving the endometrium alone in improving the pregnancy rate [RR pregnancy rate=1.35, 95% CI(1.23, 1.48)]. Ding kundan combined with clomiphene was more effective than clomiphene alone in regulating endometrial thickness and reducing follicle-stimulating hormone and estradiol levels [MDendometrial thickness=3.34, 95% CI(3.27, 3.41), MD follicle-stimulating hormone=-0.42, 95% CI(-0.65,-0.19), MDestradiol=-4.33, 95% CI(-8.18,-0.48)]. Dingkundan combined with letrozole was superior to letrozole alone in increasing the follicle-stimulating hormone level and reducing the estradiol level [MD follicle-stimulating hormone=1.14, 95% CI(0.49, 1.78), MDestradiol =-33.65, 95% CI (-59.13,-8.17)]. The single-study results showed that Dingkundan combined with conventional western medicine had certain advantages in regulating endometrial thickness, reducing follicle-stimulating hormone, luteinizing hormone, and estradiol levels, and increasing progesterone levels. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for the evaluation of outcome indicators. The results showed that the quality of the evidence was graded moderate or low. Based on the existing evidence, Ding kundan combined with western medicine for infertility treatment had certain advantages in increasing the pregnancy rate, improving endometrial thickness, regulating hormone levels, and reducing adverse reactions. However, affected by the quality of the included trials, the results may have limitations, and high-quality RCTs are needed for verification in the future.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Xu, X., et al. (2022). "Safety Warning about Laparoscopic Power Morcellation in Hysterectomy: A Cost-Effectiveness Analysis of National Impact." Women's health reports (New Rochelle, N.Y.) 3(1): 369-384.
	Background: Following a 2014 safety warning (that laparoscopic power morcellation may increase tumor dissemination if patients have occult uterine cancer), hysterectomy practice shifted from laparoscopic to abdominal approach. This avoided morcellating occult cancer, but increased perioperative complications. To inform the national impact of this practice change, we examined the cost-effectiveness of hysterectomy practice in the postwarning period, in comparison to counterfactual hysterectomy practice had there been no morcellation warning.; Materials and Methods: We constructed a decision tree model to simulate relevant outcomes over the lifetime of patients in the national population undergoing hysterectomy for presumed benign indications. The model accounted for both hysterectomy- and occult cancer-related outcomes. Probability-, cost-, and utility weight-related input parameters were derived from analysis of the State Inpatient Databases, State Ambulatory Surgery and Services Databases, data from the New York Statewide Planning and Research Cooperative System and New York State Cancer Registry, and published literature.; Results: With an estimated national sample of 353,567 adult women, base case analysis showed that changes in hysterectomy practice after the morcellation warning led to a net gain of 867.15 quality-adjusted life years (QALYs), but an increase of $19.54 million in costs (incremental cost-effectiveness ratio = $22,537/QALY). In probabilistic sensitivity analysis, the practice changes were cost-effective in 54.0% of the simulations when evaluated at a threshold of $50,000/QALY, which increased to 70.9% when evaluated at a threshold of $200,000/QALY.; Conclusion: Hysterectomy practice changes induced by the morcellation warning are expected to be cost-effective, but uncertainty in parameter values may affect the cost-effectiveness results.; Competing Interests: V.B.D. is an employee of CooperSurgical, Inc., with an adjunct faculty appointment with Yale University. C.P.G. has received grant funding for research distinct from this project from the National Comprehensive Cancer Network (NCCN) Foundation (Pfizer/Astra-Zeneca), Genentech, and Johnson & Johnson. J.D.W. has received research funding from Merck, as well as royalties from UpToDate, Inc. The other authors have no conflict of interest to declare. (© Xiao Xu et al., 2022; Published by Mary Ann Liebert, Inc.)

Xu, Y., et al. (2022). "Clinical efficacy and safety of the Jinfeng pill in the adjuvant treatment of infertility in patients with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trial." Annals of Palliative Medicine 11(1): 352-362.
	Background: Polycystic ovary syndrome (PCOS) is a common endocrine disease leading to infertility in women of childbearing age. Adjuvant therapy with Jinfeng pills (a traditional Chinese medicine) can increase ovarian blood flow, regulate female endocrine levels, and achieve good therapeutic effect. A systematic review and meta-analysis were conducted to examine the efficacy and safety of Jinfeng pills.; Methods: The PubMed (2000 to August 2021), Excerpta Medica Database (2000 to August 2021), Chinese Biomedical Literature (2000 to August 2021), and China National Knowledge Infrastructure (2000 to August 2021) databases were searched. All patients with PCOS were included in the randomized controlled study of Jinfeng pills combined with an adjuvant Western medicine treatment. After screening and a risk of bias assessment, Stata16.0 software was used for the analysis.; Results: A total 7 of articles (comprising 691 patients; 26-83 participants per group) were included in the meta-analysis. The meta-analysis showed that the effective rate the experimental group treated with Jinfeng pills combined with adjuvant Western medicine was higher than that of the control group treated with Western medicine only [relative risk (RR) =1.15, 95% confidence interval (CI): 1.03 to 1.28; P=0.015]. After treatment, the follicle-stimulating hormone level of the experimental group was significantly lower than that of the control group [mean difference (MD) =-5.10, 95% CI: -7.95 to -2.24; P=0.0005], the estradiol level of the experimental group was significantly higher than that of the control group (MD =10.74, 95% CI: 4.19 to 17.29; P=0.001), the testosterone level of the experimental group was significantly lower than that of the control group (MD =-1.17, 95% CI: -2.09 to -0.25; P=0.01), and the pregnancy rate of the experimental group was significantly higher than that of the control group (RR =1.36, 95% CI: 1.13 to 1.64; Z=3.183; P=0.001).; Discussion: The therapeutic effect of Jinfeng pills combined with Western medicine in treating PCOS was better than that of Western medicine alone, and there was no increase in adverse reactions.

Xu, Y., et al. (2021). "Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis." Taiwanese Journal of Obstetrics & Gynecology 60(3): 433-441.
	Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73-0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.; Competing Interests: Declaration of competing interest The authors declare there was no conflict of interest. (Copyright © 2021. Published by Elsevier B.V.)

Xu, Z., et al. (2024). "Comparative efficacy of different growth hormone supplementation protocols in improving clinical outcomes in women with poor ovarian response undergoing assisted reproductive therapy: a network meta-analysis." Scientific Reports 14(1): 3377.
	Growth hormone (GH) has a long-standing history of use as an adjunctive therapy in the treatment of poor ovarian response (POR), but the optimal dosage and timing remains unclear. The aim of this study was to evaluate and compare the efficacy of different GH supplementation protocols through a network meta-analysis (NMA) and determine the optimal treatment protocol. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. Databases including PubMed, Web of Science, Cochrane Library and Embase were searched until June 2023. A total of 524 records were retrieved in our search, and 23 clinical studies comprising 4889 cycles were involved. Seven different GH protocols were identified. Results showed that compared to the control group, daily administration of 4-8 IU of GH during the follicular phase of the stimulation cycle had the best comprehensive therapeutic effects on improving the number of retrieved oocytes, mature oocytes, endometrial thickness, and reducing gonadotropin requirements in POR patients undergoing assisted reproductive therapy, with a relatively brief treatment duration and a moderate total GH dose. Subgroup analysis demonstrated that this protocol could significantly improve the clinical pregnancy rate of POR patients in the randomized controlled trials (RCT) subgroup and the African subgroup. Therefore, its clinical application is suggested. Besides, the potential advantages of long-term GH supplementation protocol (using GH for at least 2 weeks before oocyte retrieval) has merit for further research. Rigorous and well-designed multi-arm RCTs are needed in the future to confirm the conclusions drawn from this study.

Xuan, M., et al. (2022). "Role of ultrasound-guided technique in the treatment of gynecologic diseases: A systematic review and meta-analysis." Medicine (United States) 101(43): E31329.
	Background: The efficacy and safety of ultrasound-guided interventional procedures for gynecologic diseases have not been evaluated comprehensively. Therefore, we aimed to provide an evidence-based medical reference for clinical treatment in this meta-analysis. Method(s): The literature searches were conducted in databases of PubMed, Embase, and Web of Science for eligible studies published from 2002 to May 2022. All literature was searched, screened, and reviewed by 2 researchers separately. RevMan 5.3.0 was used to analyze the relevant data. Result(s): A total of 12 articles consisting of 2854 patients were included. Compared with the control group, meta-analysis showed that ultrasound-guided technique in the experimental group was associated with a higher effective rate [risk ratio = 0.84, 95% confidence interval (CI) (0.84, 0.84)], a lower probability of recurrence [odds ratio = 0.13, 95% CI (0.13, 0.13), P <.00001], and a greater effective reintervention rate [odds ratio = 3.39, 95% CI (1.29, 8.86), P =.01]. However, it was not significantly associated with fewer adverse reactions. Conclusion(s): Ultrasound-guided technique in treating gynecologic diseases exerted a positive effect and had fewer adverse reactions, which could be popularized and applied in clinical practice.Copyright © 2022 the Author(s).

Xuan, Y., et al. (2022). "The efficacy and safety of simple-needling for the treatment of primary dysmenorrhea compared with ibuprofen: A systematic review and meta-analysis." Medicine 101(7): e28919.
	Background: Needling and ibuprofen are often used clinically to treat primary dysmenorrhea (PD). However, the difference between the efficacy and safety of the treatment of PD is not clear. This study evaluates the efficacy and safety of simple-needling for PD patients through a comparison with ibuprofen.; Methods: A comprehensive search of 7 electronic databases and relevant medical journals, from the establishment of the publication to December 2020. The Cochrane risk of bias tool was used to evaluate the methodological quality of randomized clinical trials (RCTs) that met the inclusion criteria, and a meta-analysis was performed with the Review Manager version (RevMan version 5.3).; Results: Twenty three RCTs were included. The meta-analysis reported that simple-needling groups had better than ibuprofen groups on cure rate (relative risk = 2.29, 95% CI [1.96, 2.68], P < .00001) and total effective rate (relative risk = 1.24, 95% CI [1.19, 1.29], P < .00001) and VAS score (MD = -1.24, 95% CI [-1.92, -0.55], P = .0004). Seven studies reported adverse events, of which 4 studies had mild adverse events.; Conclusion: Simple-needling is superior to ibuprofen treatment in terms of clinical efficacy and improvement of pain symptoms. A small number of studies reported whether simple-needling produced adverse events, so there is not enough evidence to support the safety of simple-needling in the treatment of PD.; Prospero Registration Number: CRD42021233403.; Competing Interests: The authors have no conflicts of interests to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Xue, Y. and F. Zhao (2023). "Effect of bevacizumab in combination with chemotherapy for ovarian cancer on wound healing in patients: A meta-analysis." International wound journal.
	In this meta-analysis, we reviewed the findings and definitive findings of a new study that assessed the impact of bevacizumab on wound healing following combined chemotherapy for ovarian cancer (OC). The results of a controlled study that assessed the efficacy of bevacizumab in the treatment of ovarian cancer were retrieved from 4 databases, such as the Web of Science and EMBASE. The results of the adverse event associated with wound healing were determined by comparison of the controlled studies of bevacizumab plus chemotherapy in the treatment of ovarian cancer. A meta-analysis was conducted with either a randomized or a fixed-effect model in order to establish an odds ratio for time to event variables and for a binary outcome. In the research literature, 830 trials have been identified and seven have been chosen to be included in a definitive analysis of the trial. Among the 4134 cases who received chemotherapy after operation, 2098 received standard chemotherapy and 2036 received the addition of bevacizumab. A total of 7 trials have shown that the use of bevacizumab in the treatment of ovarian cancer patients has reduced wound healing (OR, 0.55; 95% CI: 0.37, 0.80, p = 0.002). Four trials demonstrated that there was no change in the incidence of haemorrhage in patients with ovarian cancer when administered with or without bevacizumab (OR, 0.48; 95% CI, 0.10, 2.34, p = 0.37). The combined use of bevacizumab and chemotherapy may have a negative effect on the healing of wound. (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

xuesong, d., et al. (2022). "Adverse events of VEGFR-associated multi-targeted Tyrosine kinase inhibitor Lenvatinib for gynecological cancer patients in Clinical trials: A systematic review and meta-analysis."
	
Xueying, L., et al. (2022). "The effectiveness of expressive writing therapy for postpartum mothers’ psychological health: Protocol for a systematic review and meta-analysis."
	
Xuhui, Z., et al. (2021). "The role of gabapentin in chronic pelvic pain: a systematic review and meta-analysis."
	
Xuji, J., et al. (2023). "Different interventions for vulvar lichen sclerosis: a systematic review and network meta-analysis."
	
Yabuno, A. and K. Hasegawa (2021). "Ⅰ. Secondary Cytoreductive Surgery for Platinum-Sensitive Recurrent Ovarian Cancer -Review and Consideration from Recent International Phase Ⅲ Trials." Gan to kagaku ryoho. Cancer & chemotherapy 48(2): 191‐194.
	
Yadav, S., et al. (2023). "Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis." ELife 12.
	Background: Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority.; Methods: Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian-Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale.; Results: We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32-1.52) for anxiety, 1.65 (95% CI: 1.44-1.89) for depression, 1.48 (95% CI: PR: 1.06-2.05) for eating disorders, and 1.20 (95% CI: 0.96-1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD.; Conclusions: Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder.; Funding: The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence.; Competing Interests: SY, OD, AB, DM, RB No competing interests declared, WP is a Director of Public Affairs, Study Recruitment and Patient Registry Manager, and Intern Preceptor for PCOS Challenge: The National Polycystic Ovary Syndrome Association. The author has no other competing interests to declare, SO received honoraria from Institute for Family Centeredness; has received travel support for attendance at Women's Health Innovation Summit; and is Executive Director for PCOS Challenge: The National Polycystic Ovary Executive Director Syndrome Association. The author has no other competing interests to declare, RA received a grant from Ferring Pharmaceuticals; has received royalties from Wolters Kluwer Health, Johns Hopkins University Press, Springer, and McGraw Hill; has received honoraria from Davidson Mestman course; has participated on a data safety monitoring board for University of Michigan and Guangzhou Medical University; has held a leadership or fiduciary role at American Society for Reproductive Medicine; holds stock at Martin Imaging and Arora Forge; has received consulting fees from Spruce Biosciences, Fortress Biotech, Rani Therapeutics, Core Access Surgical for PCOS, female reproduction and gynecologic surgery; and serves as Senior Editor at eLife. The author has no other competing interests to declare (© 2023, Yadav et al.)

Yagci, N., et al. (2023). "Long-Term Follow-Up Result of Connective Tissue Manipulation in Young Women with Primary Dysmenorrhea: Different Intervention Durations." Reproductive sciences (Thousand Oaks, Calif.) 30(7): 2198-2209.
	The purpose of this study was to reveal the effect of connective tissue manipulation (CTM) on long-term pain severity, fatigue, sleep quality, premenstrual symptom severity, general health status, anxiety, and depression in women with primary dysmenorrhea (PD). Thirty-five women with PD were divided into two groups. CTM was applied to the participants in each group on the days when they were not on menstruation between two menstrual cycles for the group 1 (n=18) and between three menstrual cycles for the group 2 (n=17). Intensity of menstrual pain, the sleep quality, and fatigue status of the participants during dysmenorrhea were evaluated by the Visual Analog Scale (VAS). Depressive symptoms and anxiety were evaluated using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI), respectively. Also, the Premenstrual Syndrome Scale (PMSS) and the General Health Questionnaire (GHQ) were used to investigate the severity of premenstrual symptoms and mental health status during menstrual period. A significant decrease in the pain severity and fatigue of the participants was observed in both group 1 and group 2 after treatment, after 3rd, and 6th month follow-up (p=0.001). Also, this decrease lasted for 12th month follow-up after treatment in group 2 (p=0.0001). There was no statistically significant improvement in sleep quality within each group (p>0.05). Moreover, none of the parameters were significantly different between two groups (p>0.05). We can suggest that 2-cycle CTM treatment should be preferred in clinical settings to obtain long-lasting effects for decreasing pain, fatigue, and premenstrual symptoms in women with PD. CLINICAL TRIAL NUMBER: NCT04509934. Registration date: 8 November 2020. (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Yagi, T., et al. (2022). "Safety and efficacy of Ninjin'yoeito along with iron supplementation therapy for preoperative anemia, fatigue, and anxiety in patients with gynecological disease: an open-label, single-center, randomized phase-II trial." BMC Women's Health 22(1): 229.
	Background: Preoperative anemia affects perioperative outcomes and often causes fatigue and psychological disorders. Therefore, anemia should be treated before a patient undergoes surgery. Ninjin'yoeito (NYT), a Japanese Kampo medicine composed of ginseng and Japanese angelica root with the other 10 herbs, is administered for anemia, fatigue and anxiety; however, there are a few reports that have prospectively examined the effects of NYT before surgery for gynecological diseases. Hence, we tended to investigate its efficacy and safety. Method(s): In this open-label randomized trial, women with gynecological diseases accompanied by preoperative anemia (defined as < 11.0 g/dL Hemoglobin [Hb]) were randomly assigned (1:1) into the iron supplementation and NYT groups. Patients of the iron supplementation group and the NYT group received 100 mg/day iron supplementation with and without NYT (7.5 g/day) for at least 10 days before surgery. The primary endpoint was improvement in Hb levels before and after treatment, and Cancer Fatigue Scale (CFS) and Visual Analogue Scale for Anxiety (VAS-A) scores between groups. Statistical analyses were performed with Wilcoxon signed rank test, Wilcoxon rank sum test, and Fisher's exact test as appropriate. Result(s): Forty patients were enrolled of whom 30 patients were finally analyzed after allocating 15 to each group. There was no difference in the characteristics between both groups. Hb significantly increased in both groups (iron supplementation group, 9.9 +/- 0.8 g/dL vs. 11.9 +/- 1.6 g/dL; NYT group, 9.8 +/- 1.0 g/dL vs. 12.0 +/- 1.0 g/dL); the difference in the elevations in Hb between both groups was statistically insignificant (P = 0.72). Contrarily, CFS (17.9 +/- 10.2 vs. 8.1 +/- 5.2) and VAS-A (56 mm (50-70) vs. 23 mm (6-48)) scores were significantly decreased only in the NYT group and these changes were greater in the NYT group (CFS, P = 0.015; VAS-A, P = 0.014). Liver dysfunction occurred in one patient of the NYT group. Conclusion(s): For treating preoperative anemia in women with gynecological conditions, NYT administration along with iron supplementation safely and efficiently improved the preoperative fatigue and anxiety in addition to the recovery from anemia. Trial registration: jRCT1051190012 (28/April/2019, retrospectively registered).Copyright © 2022, The Author(s).

Yakin, K., et al. (2019). "Intrauterine administration of peripheral mononuclear cells in recurrent implantation failure: a systematic review and meta-analysis." Scientific Reports 9(1): 3897.
	It has been proposed that intrauterine administration of peripheral blood mononuclear cells (PBMCs) modulates maternal immune response through a cascade of cytokines, chemokines and growth factors to favor implantation. We conducted a meta-analysis to verify the effect of intrauterine PBMC administration on the outcome of embryo transfer in women with recurrent implantation failure (RIF). All relevant trials published in PubMed, Web of Science and Cochrane library databases were searched. Two randomized controlled trials and three cohort studies (1173 patients in total) matched the inclusion criteria. No differences in live birth rates were seen between the PBMC-treated patients and controls (OR: 1.65, 95% CI: 0.84-3.25; p = 0.14; I 2 : 66.3%). The clinical pregnancy rate was significantly higher in women who received intrauterine PBMCs before embryo transfer compared with those who did not (OR: 1.65, 95% CI: 1.30-2.10; p = 0.001, heterogeneity; I 2 : 60.6%). Subgroup analyses revealed a significant increase in clinical pregnancy rates with the administration of PBMCs in women with ≥3 previous failures compared with controls (OR: 2.69, 95% CI: 1.53-4.72; p = 0.001, I 2 : 38.3%). In summary, the data did not demonstrate an association between the administration of PBMCs into the uterine cavity before fresh or frozen-thawed embryo transfer and live birth rates in women with RIF. Whether intrauterine PBMC administration significantly changes live birth and miscarriage rates requires further investigation.

Yakit, Y., et al. (2022). "Comparing the efficacy of the Knack maneuver on pelvic floor muscle function and urinary symptoms using different teaching methods: a prospective, nonrandomized study." International Urogynecology Journal 33(10): 2895-2903.
	Introduction and hypothesis: This study was aimed at comparing the efficacy of Knack maneuver training taught using different techniques on pelvic floor muscle (PFM) function, urinary symptoms, and perception of improvement in women with stress urinary incontinence (SUI). Method(s): We conducted a prospective nonrandomized study of 46 women with SUI. Assessments included: PFM functions (secondary outcome, SO) using a Myomed 932 EMG biofeedback device, urinary incontinence symptoms using the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form (ICIQ-SF; primary outcome), the Urogenital Distress Inventory-6 (UDI-6; SO), and the Incontinence Severity Index (ISI; SO), and perception of improvement using the Global Perceived Impact scale. The women were divided into three groups according to their preference: group 1 (Knack maneuver training with electromyography biofeedback), group 2 (Knack maneuver training with verbal instruction), and group 3 (Knack maneuver training with vaginal palpation). An education program was also given to all women individually. The training program was 1 day per week for 4 weeks. Result(s): There was an improvement in UDI-6, ICIQ-SF, and ISI scores in all groups (p<0.05). The maximum voluntary contraction (MVC) of the PFMs increased in group 2 (p=0.002), whereas both the MVC of PFMs and PFM contraction during Valsalva increased in group 3 (p=0.011 and p=0.042). Conclusion(s): Regardless of the teaching methods, the Knack maneuver and education programs were effective on urinary symptoms in women with mild to moderate SUI. The Knack maneuver training with vaginal palpation and verbal instruction improved MVC of PFMs. All three different teaching methods might be used in SUI treatment programs.Copyright © 2022, The International Urogynecological Association.

Yakushevskaya, O. V., et al. (2022). "IMPACT OF MENOPAUSAL HORMONE THERAPY ON THE DEVELOPMENT AND PROGRESSION OF CERVICAL AND ENDOMETRIAL CANCERS." Akusherstvo i Ginekologiya (Russian Federation) 2022(8): 30-35.
	Antitumor therapy for malignant diseases of the reproductive system is often accompanied by the development of induced menopause. Studying the possibility of safely prescribing menopausal hormone therapy (MHT) in this group of patients is an urgent task, since most patients have to deal with the consequences of estrogen deficiency states after antitumor therapy for many years. The review analyzes the available information on the rate of progression/recurrence of the neoplastic process in cervical cancer/endometrial cancer (CC/EC) survivors during MHT. Articles were sought in accordance with the recommendations of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) presented in PubMed and SCOPUS. The use of MHT was evaluated in two ways: 1) as a risk factor for CC/EC in women without a history of this pathology and 2) as a risk factor for CC/EC recurrence/progression. Analyzing the available publications revealed no reliable evidence for the negative effect of MHT on the outcomes of CC/EC. To prescribe MHT after favorable completion of antitumor therapy in patients with a history of squamous cell CC has long been a routine practice. With hormone-dependent SC/EC in young women with induced menopause, the possibility of using MHT should be resolved in favor of the existing advantages (in reducing the risk of age-associated pathology and in improving the quality of life) and assessing the corresponding risks. Conclusion(s): The possibility of prescribing MHT to patients with a history of cancer should be discussed within the framework of a council of physicians, such as a gynecological oncologist, a chemotherapist, and an obstetrician/ gynecologist. Further prospective and randomized studies are needed to fully evaluate the impact of MHT on oncological outcomes in CC/EC survivors.Copyright © A group of authors, 2022.

Yale, U. (2021). "Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis." ClinicalTrials.gov.
	A Phase 3 randomized clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators\' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to placebo.

Yali, C. (2020). "Meta analysis of the clinical efficacy of acupuncture in the treatment of stress urinary incontinence in women." 中国中医药现代远程教育 18(3): 142-144.
	Objective To analyze the clinical efficacy of acupuncture in the treatment of stress urinary incontinence in women, to provide corresponding reference for clinical treatment. Clinical randomized controlled trials of stress urinary incontinence in women, In addition to the revised Jadad scale evaluation criteria of RCT quality evaluation, quality evaluation of the included literature and analysis using Revman 5.3 to evaluate the clinical efficacy of acupuncture in the treatment of stress urinary incontinence in women. The results of the analysis show that acupuncture treatment methods are associated with There are significant statistical differences in clinical efficacy of methods such as rehabilitation training. Conclusion The clinical efficacy of acupuncture in the treatment of stress urinary incontinence in women is significantly better than treatments such as pelvic floor muscle exercise, but in view of the low Jadad score of the literature included in the study, further studies are still needed to be included in high-quality literature for validation.

Yalle-Vásquez, S., et al. (2022). "Vitamin E supplementation improves testosterone, glucose- and lipid-related metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(7): 548-557.
	Aim: This systematic review and meta-analysis assessed the effect of vitamin E supplementation on testosterone, glucose, lipid profile, pregnancy rate, hirsutism, and body mass index (BMI) in women with polycystic ovary syndrome (PCOS).; Methods: A multi-database search was performed from inception to January 2022 for randomized controlled trials (RCTs) reporting the effects of vitamin E supplementation with or without another nutritional supplement on women with PCOS. A random-effects model was used to obtain mean differences (MDs) and its 95% confidence intervals (95%CI). Evidence certainty was assessed with GRADE methodology.; Results: We meta-analyzed eight RCTs reporting vitamin E supplementation alone or combined with other individual substances like omega-3, vitamin D3, or magnesium oxide in adult women ≤40 years old with PCOS. Vitamin E supplementation reduced fasting glucose (MD: -1.92 mg/dL, 95%CI: -3.80 to -0.05), fasting insulin (MD: -2.24 µIU/mL, 95%CI: -3.34 to -1.14), HOMA-IR (MD: -0.42, 95%CI: -0.65 to -0.19), total cholesterol (MD: -18.12 mg/dL, 95%CI: -34.37 to -1.86), LDL-cholesterol (MD: -15.92 mg/dL, 95%CI: -29.93 to -1.90), triglycerides (MD: -20.95 mg/dL, 95%CI: -37.31 to -4.58), total testosterone (MD: -0.42 ng/mL, 95%CI: -0.55 to -0.29), and increased sex hormone-binding globulin (MD: 7.44 nmol/L, 95%CI: 2.68 to 12.20). However, it had no impact on female sex hormones, HDL-cholesterol, BMI, and hirsutism. Two RCTs assessed pregnancy and implantation rates with inconsistent results. The certainty of the evidence was very low to moderate.; Conclusion: Vitamin E supplementation improves glucose, lipid, and androgenic-related biomarkers in women with PCOS.

Yamada, H., et al. (2023). "High doses of intravenous immunoglobulin stimulate regulatory T cell and suppress natural killer cell in women with recurrent pregnancy loss." Journal of Reproductive Immunology 158: 103977.
	The aim was to evaluate whether natural killer (NK) cells and regulatory T (Treg) cells were involved in mechanisms underlying beneficial effects of a high dose of intravenous immunoglobulin (IVIG) on recurrent pregnancy losses (RPL) of unexplained etiology. In a double‐blind, randomized, placebo‐controlled trial of IVIG (400 mg/kg, for 5 days in 4–6 weeks of gestation) in women with RPL, blood samples were collected pre‐infusion, one week after infusion (1 w), and eight weeks of gestation/when miscarried (8 w). Levels of NK and Treg cells in peripheral blood were compared between women with IVIG (n = 50) and placebo (n = 49), and between women with IVIG who gave live birth (n = 29) and those who had miscarriage with normal chromosome (n = 12). Effector Treg cell percentages in IVIG group at 1 w (mean 1.43 % vs. 1.03 %) and at 8 w (1.91 % vs. 1.18 %) were higher than those in placebo group (p < 0.01). Total Treg cell percentages in IVIG group at 1 w (4.75 % vs. 4.08 %) and at 8 w (5.55 % vs. 4.47 %) were higher than those in placebo group (p < 0.05). In women with live birth, total Treg cell percentages increased at 8 w (5.52 %, p < 0.001) compared with pre‐infusion (4.54 %) and 1 w (4.47 %), while NK cell activity decreased at 1 w (20.18 %, p < 0.001) compared with pre‐infusion (26.59 %). IVIG increased Treg cell percentages and suppressed NK cell activity very early in pregnancy, and these were associated with subsequent live birth. Stimulation of Treg cells and suppression of NK cell activity very early in pregnancy may be a mechanism of pharmacological effects of high dose IVIG.

Yamaguchi, M., et al. (2023). "Efficacy of estrogen-progestogen therapy for women with vascular retained products of conception following miscarriage or abortion." Taiwanese Journal of Obstetrics & Gynecology 62(5): 661-666.
	Objective: To assess the clinical characteristics and endocrinological background of women with vascular retained products of conception (RPOC) after miscarriage or abortion and evaluate the effect of estrogen-progestogen therapy (EPT) as an initial treatment on this population based on their endocrinological background.; Materials and Methods: Women with vascular RPOC after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (conjugated estrogen and norethisterone) were retrospectively reviewed. Their clinical characteristics, hormonal parameters, ultrasonographic findings, and outcomes were evaluated.; Results: Of 35 women with vascular RPOC, 30 (86%) presented with vaginal bleeding at a visit, and 6 (17%) required inpatient management due to heavy bleeding. Among women who presented with vaginal bleeding, serum progesterone levels were significantly lower (0.25 vs. 6.5 ng/mL, p = 0.004) than those in women who did not present with vaginal bleeding. There were no differences in serum hCG levels (10.5 vs. 3.1 mIU/mL) or serum estradiol levels (65.4 vs. 162.3 pg/mL). After withdrawal bleeding following the first course of EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and 23 (66%) of all women had a thin and linear endometrium. All women could be treated by up to two courses of EPT and did not require additional interventions. The median duration to hCG normalization after the initial EPT was 24.5 (9-88) days.; Conclusion: Women with vascular RPOC who have no bleeding had significantly higher levels of serum progesterone, indicating that administration of progestogen may have an effect on hemostasis. Endometrial bleeding can be prevented or stopped, and retained tissues can be conservatively expelled by oral administration of EPT, including norethisterone, in women with vascular RPOC.; Competing Interests: Conflicts of interest The authors declare no conflicts of interest. (Copyright © 2023. Published by Elsevier B.V.)

Yamaguchi, M., et al. (2022). "Efficacy of hormonal therapy for vascular retained products of conception based on endocrinological background." Placenta 128: 129-130.
	Objective: To discuss the pathogenesis of vaginal bleeding associated with vascular retained products of conception (RPOC) and evaluate the effect of estrogen -progestogen therapy (EPT) on women with vascular RPOC based on their endocrinological background. Method(s): Women with vascular RPOC were divided into two groups of those after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (M/A group) and those after delivery at more than 20 weeks of pregnancy (D group). Hormonal parameters were compared according to the presence of vaginal bleeding in M/A group and outcomes after EPT were evaluated in both groups. Result(s): Of 35 women in the M/A group, 30 (85.7%) presented with vaginal bleeding at a visit. Among 5 who did not present with it, serum progesterone levels were significantly higher (0.25 vs. 6.5 ng/mL, p=0.004) than those in women who presented with it. There were no differences in serum hCG levels or serum estradiol levels. After the initial EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and all women were treated by up to two cycles of EPT and did not require additional interventions. Of 13 women in the D group, 5 (38.4%) pregnancies were conceived with hormonal replacement cycles, and two were diagnosed with CAOS and required blood transfusions during pregnancy. The median weeks of delivery was 39 (21-41) weeks, and three (23.0%) required maternal transport due to bleeding exceeding 3 L at delivery. It was difficult to discriminate between lochia and bleeding at the diagnosis of vascular RPOC. Nine was given EPT, and all were treated by up to two cycles. Conclusion(s): Anovulatory breakthrough bleeding may occur in women with vascular RPOC after miscarriage or abortion. EPT containing norethisterone was shown to be effective for women with vascular RPOC regardless of gestational age.Copyright © 2022

Yamaji, N., et al. (2023). "Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis." Children 10(3): 443.
	This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.Copyright © 2023 by the authors.

Yamamoto, A., et al. (2021). "Sebaceous carcinoma of the vulva treated with sentinel lymph node biopsy: a case report and literature review." Int. Cancer Conf. J. 10(3): 239-243.
	
Yan, H., et al. (2022). "Effect of mindfulness-based interventions on mental health of perinatal women with or without current mental health issues: A systematic review and meta-analysis of randomized controlled trials." Journal of Affective Disorders 305: 102-114.
	BACKGROUND: The effectiveness of mindfulness-based interventions (MBIs) on the mental health of perinatal women with or without current mental health issues remains unclear. METHODS: Four electronic databases were searched from inception to October 1, 2021. Data synthesis, sensitivity analysis, subgroup analysis, and quality assessment were performed on the included studies. I2 and Q tests were applied to evaluate heterogeneity across studies. The risk of publication bias was assessed and visualized using a funnel plot. RESULTS: A total of 21 RCTs with 1765 perinatal women were enrolled in the meta-analysis. We found MBIs were effective in reducing depression, anxiety, and stress, as well as increasing mindfulness in perinatal women with current mental health issues. However, MBIs were not prior to controls in reducing depression and stress, and increasing mindfulness in perinatal women without current mental health issues. The effectiveness of MBIs on reducing anxiety in perinatal women without current mental health issues was unclear. LIMITATIONS: Considerable heterogeneity was found in the pooled analyses of the RCTs in depression and anxiety in perinatal women with mental health issues and stress in perinatal women without mental health issues. CONCLUSION: MBIs could serve as a useful addition to existing support for perinatal women with current mental health issues. However, further studies were needed to explore and prove the effectiveness of MBIs on the mental health of perinatal women without current mental health.

Yan, L., et al. (2022). "High-intensity focused ultrasound treatment for symptomatic uterine fibroids: a systematic review and meta-analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 39(1): 230-238.
	Objective: This study was aimed at comparing the outcomes of high-intensity focused ultrasound (HIFU) with those of uterine artery embolization (UAE) and traditional surgeries for treating symptomatic uterine fibroids.; Materials and Methods: We searched the following databases from their beginning to 5 November 2021: PubMed, Medline, Embase and Cochrane Library.; Results: Overall, 21 studies were included in this meta-analysis. The results revealed that HIFU had a higher re-intervention rate than UAE (relative risk [RR] = 4.06, 95% confidence interval [CI]: 2.47-6.69) and offered no significant advantages in reducing the symptom severity score (SSS) (mean difference [MD] = 17.01, 95% CI: 10.25-23.77) and improving the health-related quality of life (HRQoL) score (MD= -18.32, 95% CI: -24.87 to -11.78) in the treatment of symptomatic uterine fibroids. However, compared with UAE, HIFU may be associated with a higher pregnancy rate (RR = 17.44, 95% CI: 2.40-126.50) and may have a significant advantage in shortening pregnancy interval and preserving ovarian function. Moreover, upon comparing HIFU with traditional surgical treatments, the HIFU group showed significantly improved HRQoL score (MD = 2.25, 95% CI: 1.15-3.35), but the re-intervention rate (RR = 1.65, 95% CI: 0.59-4.57), pregnancy rate (RR = 1.01, 95% CI: 0.90-1.13), SSS and ovarian function did not significantly differ between the two groups.; Conclusions: Although HIFU has relatively high re-intervention rate, it may offer a higher pregnancy rate and shorter pregnancy interval with little influence on ovarian function, thus making it an attractive option for treating symptomatic fibroids in young women who wish to plan a pregnancy in the future.

Yan, L.-J., et al. (2023). "Effectiveness and Safety of Chinese Medicine at Shenque (CV 8) for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Chinese Journal of Integrative Medicine 29(4): 341-352.
	Background: Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD.; Objective: To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM).; Methods: China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.; Results: Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I 2 =80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I 2 =38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I 2 =63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall.; Conclusions: Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350). (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Yan, Q., et al. (2022). "The incidence of gestational diabetes mellitus among women with polycystic ovary syndrome: a meta-analysis of longitudinal studies." BMC Pregnancy and Childbirth 22(1): 370.
	Background: Previous studies have shown that polycystic ovary syndrome is a predictor of gestational diabetes mellitus, but we do not know exactly how many polycystic ovary syndrome patients may develop gestational diabetes mellitus. Currently, the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome varies greatly across studies, ranged from 4.12% to 59.50%. Besides, many factors have been found to be related to the incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, but the results among different studies are not consistent. The possible causes of inconsistencies between the current estimates were unclear. This review aimed at exploring the pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome, summarizing possible causes of the inconsistencies in the current estimates, try to provide a reference for prevention of gestational diabetes mellitus and polycystic ovary syndrome in the future.; Methods: Systematic searches of different databases (including EMBASE, Web of Science, MEDLINE, The Cochrane Library, CNKI and PubMed) were conducted for studies published until 31 May 2021. Statistical analyses were performed using R software, the pooled incidence of gestational diabetes mellitus among polycystic ovary syndrome patients was combined using random effects model. Cochrane's "Tool to Assess Risk of Bias in Cohort Studies" was used for quality assessment.; Results: Twenty-two longitudinal studies were included. A total of 24,574 women with polycystic ovary syndrome were identified in the 22 articles, of which 4478 were reported with gestational diabetes mellitus. The pooled incidence of gestational diabetes mellitus among women with polycystic ovary syndrome was 20.64%, with a 95% CI of 14.64% to 28.30%. In the meta-regression model, several variables including age, area, quality score and sample size were suggested as significant sources of heterogeneity, accounted for 77.57% of the heterogeneity across studies.; Conclusions: Evidence in this review suggests that gestational diabetes mellitus were common among women with polycystic ovary syndrome. More research is needed to found effective interventions for preventing gestational diabetes mellitus among women with polycystic ovary syndrome. (© 2022. The Author(s).)

Yan, R.-N., et al. (2020). "Primary radical hysterectomy vs chemoradiation for IB2-IIA cervical cancer: A systematic review and meta-analysis." Medicine 99(5): e18738.
	Background: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer.; Methods: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed.; Results: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021).; Conclusion: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.

Yan, V. H., et al. (2022). "Progestogens in the management of miscarriage and preterm birth." Medical Journal of Malaysia 77(4): 512-518.
	Miscarriage affects up to 20% of pregnant women, resulting in substantial psychological repercussions in addition to inherent problems from bleeding and infection. Preterm births constitute about 7-12% of all births but are over represented in terms of perinatal morbidity and mortality. Despite existing trials examining the use of progestogens in both these conditions, there is a dearth of guidelines for the practicing clinician. A systematic review of the literature was performed by an expert panel formed by the Obstetrical & Gynaecological Society of Malaysia from the inception of the databases searched up to February 2020, without language restrictions. The level of evidence and recommendations was determined by the panel and peer-reviewed by local and international experts. The use of progestogens is recommended in women with threatened miscarriages who have experienced previous miscarriage as luteal phase support in women undergoing assisted reproduction and in women with short cervix of <25mm in the midtrimester. In addition, it can be considered in women with recurrent miscarriage, where no other cause is identified. This article reviews the existing evidence including the guideline above and is intended to aid primary care doctors and obstetricians in their prescribing practices when managing these common conditions.Copyright © 2022, Malaysian Medical Association. All rights reserved.

Yan, Y., et al. (2022). "Adenomyosis-Associated Ischemic Stroke: Pathophysiology, Detection and Management." Brain Sciences 12(10): 1410.
	Female-specific risk factors for stroke have gradually received attention. The relationship between ischemic stroke and adenomyosis, a benign uterine disorder commonly present in parous women, is underrecognized. We aimed to provide an overview of the epidemiology, pathophysiological mechanisms, clinical characteristics, diagnostic considerations, and potential therapeutic strategies of adenomyosis-associated ischemic stroke. We shared our experience with the diagnosis and management of a patient, and summarized current findings and knowledge gaps of this disease based on previous literature. The relevant studies were searched in English and Chinese databases up to April 2022 using the keywords "ischemic stroke", "cerebral infarction" and "adenomyosis". Then, we provided a narrative review of the retrieved articles. Finally, the data of 32 cases were analyzed. We found that increased levels of carbohydrate antigen 125 and D-dimer and decreased level of hemoglobin are biomarkers of adenomyosis-associated ischemic stroke. In addition, hypercoagulability might be a key mechanism leading to thromboembolism in the cerebrovascular system. Additional studies are needed to find optimal prevention strategies for the disease. A better understanding of this "rare" pathogenesis of ischemic stroke may inform a more precise diagnosis and effective prevention strategy in middle-aged women with embolic stroke of undetermined source.Copyright © 2022 by the authors.

Yanagisawa, T., et al. (2023). "Iatrogenic ureteric injury during abdominal or pelvic surgery: a meta-analysis." BJU International 131(5): 540-552.
	Objective: To assess the incidence of ureteric injuries, clinical value of prophylactic ureteric stenting and impact of intra- or postoperative detection of ureteric injuries in patients treated with gynaecological or colorectal surgery. Method(s): Multiple databases were searched for articles published before September 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Studies were deemed eligible if they evaluated the differences in the rate of ureteric injuries between laparoscopic and open surgery, prophylactic ureteric stenting or not, and those of final treatment success between intra- and postoperative detection in patients who underwent gynaecological or colorectal surgery. Result(s): Overall, 46 studies were eligible for this meta-analysis. Compared to open surgery, laparoscopic hysterectomy was associated with a higher incidence of ureteric injuries (pooled odds ratio [OR] 2.12, 95% confidence interval [CI] 1.71-2.62), but there was no statistically significant difference in colectomy (pooled OR 0.89, 95% CI 0.77-1.03). Prophylactic ureteric stenting was associated with a lower incidence of ureteric injuries during gynaecological surgery (pooled OR 0.61, 95% CI 0.39-0.96). The number needed to perform ureteric stenting to prevent one ureteric injury was 224 in gynaecological surgery. On the other hand, prophylactic ureteric stenting did not reduce the risk of ureteric injuries during colorectal surgery. Intraoperative detection of a ureteric injury was associated with a lower rate of complication management failure compared to postoperative detection (pooled OR 0.22, 95% CI 0.12-0.41). Conclusion(s): Laparoscopic hysterectomy seems to be associated with a higher rate of ureteric injuries compared to an open approach. Prophylactic ureteric stenting seems to reduce this risk during gynaecological surgery. Intraoperative detection of a ureteric injury during abdominal/pelvic surgery improves outcomes, suggesting the need for awareness and proactive problem identification. Further well-designed studies assessing the candidates who are more likely to benefit from prophylactic ureteric stenting including cost analysis are needed.Copyright © 2022 BJU International.

Yanan, C., et al. (2021). "Fresh versus frozen embryos for infertility in endometriosis."
	
Yanding, G., et al. (2021). "A Meta-analysis of Efficacy of moxibustion on menstrual irregularities."
	
Yang, C., et al. (2023). "Influence of lymphadenectomy on survival and recurrence in patients with early-stage epithelial ovarian cancer: a meta-analysis." BMC Women's Health 23(1): 474.
	Background: This meta-analysis aimed to evaluate the effectiveness of lymphadenectomy on survival and recurrence in patients with early-stage epithelial ovarian cancer (eEOC).; Methods: Relevant studies were searched from four online databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) or risk ratios (RRs) with 95% CIs were used to evaluate the effects of lymphadenectomy on overall survival (OS), progression-free survival (PFS), and recurrence rates. A subgroup analysis was performed to explore the sources of heterogeneity, followed by sensitivity and publication bias assessments.; Results: Fourteen articles involving 22,178 subjects were included. Meta-analysis revealed that lymphadenectomy was significantly associated with improved OS (HR = 0.72; 95% CI:0.61, 0.84; P < 0.001), improved PFS (HR = 0.74; 95% CI: 0.67, 0.80; P < 0.001), and reduced recurrence rates (RR = 0.72; 95% CI: 0.60, 0.85; P < 0.001). Subgroup analysis showed that factors including area, histology, and source of the control group were significantly related to improved OS and PFS in patients with eEOC. Sensitivity analysis showed that the combined results were stable and reliable, and no significant publication bias was observed.; Conclusions: Patients with eEOC can benefit from lymphadenectomy, with improved survival outcomes (OS and PFS) and a lower recurrence rate. (© 2023. BioMed Central Ltd., part of Springer Nature.)

Yang, D. N., et al. (2020). "Efficacy of intrauterine perfusion of peripheral blood mononuclear cells (PBMC) for infertile women before embryo transfer: meta-analysis." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 40(7): 961-968.
	This meta-analysis was intended to evaluate the effects of intrauterine perfusion of peripheral blood mononuclear cells (PBMC) on the pregnancy outcomes including clinical pregnancy rates, embryo implantation rates, live birth rates and miscarriage rates of infertile women who were undergoing in vitro fertilisation (IVF) treatment. By searching Pubmed, Embase database, five articles meeting the inclusion criteria were included, and 1173 women were enrolled (intrauterine PBMC group: n = 514; NO-PBMC group: n = 659). For the entire IVF/ICSI population and one or two embryo transfer failure patients, there was no significant difference in endometrial thickness, embryo implantation rates, live birth rates, and miscarriage rates between the PBMC group and NO-PBMC group. Although the clinical pregnancy rates of the PBMC group were higher than that of the NO-PBMC group, the confidence interval was close to the line of unity. As for the patients with three or more implantation failures, the clinical pregnancy rates, embryo implantation rates and live birth rates were much higher in the PBMC group than that of the NO-PBMC group. In summary, current evidence suggests that intrauterine perfusion of PBMC can significantly improve pregnancy outcomes in patients who have three or more implantation failures.Impact statement What is already known on this subject? An increasing number of studies have shown that immune cells play an important role in embryo transfer. There is no reliable evidence to confirm the clinical efficacy of intrauterine perfusion of PBMC. What do the results of this study add? The current evidence suggests that intrauterine perfusion of PBMC can significantly improve pregnancy outcomes in patients who have three or more implantation failures. What are the implications of these findings for clinical practice and/or further research? To the best of our knowledge, this meta-analysis is the first to evaluate the effect of intrauterine perfusion of PBMC on pregnancy outcomes before embryo transfer. Our study indicated that intrauterine perfusion of PBMC significantly increased clinical pregnancy rates, embryo implantation rates, and live birth rates in patients who failed more than three implants.

Yang, H., et al. (2022). "Transcutaneous electrical acupoint stimulation for pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A systematic review and meta-analysis." Frontiers in Public Health 10: 892973.
	Background: Infertility is a common health problem affecting couples of childbearing age. The proposal of in vitro fertilization-embryo transfer (IVF-ET) solves the problem of infertility to a certain extent. However, the average success rate of IVF-ET is still low. Some studies conclude that transcutaneous electrical acupoint stimulation (TEAS) could improve pregnancy outcomes in women undergoing IVF-ET, however, there is a lack of comprehensive synthesis and evaluation of existing evidence.; Objective: To conduct a systematic review and meta-analysis to assess whether TEAS is effective and safe to improve the pregnancy outcomes for women undergoing IVF-ET.; Methods: Eight online databases were searched from inception to 19 November 2021. In addition, four clinical trial registries were also searched, relevant references were screened, and experts were consulted for possible eligible studies. Randomized controlled trials (RCTs) that included patients with infertility who underwent IVF and used TEAS as the main adjuvant treatment vs. non-TEAS or mock intervention controls were included. The clinical pregnancy rate (CPR) was considered the primary outcome. High-quality embryo rate (HQER), live birth rate (LBR), biochemical pregnancy rate (BPR), ongoing pregnancy rate (OPR), early miscarriage rate (EMR), birth defects rate (BDR), and adverse events related to interventions were regarded as secondary outcomes. The selection, data extraction, risk of bias assessment, and data synthesis were conducted by two independent researchers using Endnote software V.9.1 and Stata 16.0 software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the evidence quality of each outcome.; Results: There were 19 RCTs involving 5,330 participants included. The results of meta-analyses showed that TEAS can improve CPR [RR = 1.42, 95% CI (1.31, 1.54)], HQER [RR = 1.09, 95% CI (1.05, 1.14)], and BPR [RR = 1.45, 95% CI (1.22, 1.71)] of women underwent IVF-ET with low quality of evidence, and improve LBR [RR = 1.42, 95% CI (1.19, 1.69)] with moderate quality of evidence. There was no significant difference in EMR [RR = 1.08, 95% CI (0.80, 1.45)] and BDR [RR = 0.93, 95% CI (0.13, 6.54)] with very low and moderate quality of evidence, respectively. A cumulative meta-analysis showed that the effective value of TEAS vs. controls was relatively stable in 2018 [RR = 1.52, 95% CI (1.35, 1.71)]. In addition, no serious adverse events associated with TEAS were reported.; Conclusion: Our findings suggest that TEAS may be an effective and safe adjuvant treatment for women undergoing IVF-ET to improve pregnancy outcomes. However, the current evidence quality is considered to be limited, and more high-quality RCTs are needed for further verification in the future.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?ID=CRD42021238871, identifier: CRD42021238871.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yang, Hu, Xu, Yin, Yu, Liu, Xiao, Zheng, Yang and Liang.)

Yang, J., et al. (2020). "Acupuncture and related therapies for stress urinary incontinence: A protocol for systematic review and network meta-analysis." Medicine (United States) 99(28): E21033.
	Background:Stress urinary incontinence (SUI) is the most common type of urinary incontinence, affecting patients' quality of life and sexual function. Lots of Clinical trials suggested that acupuncture is beneficial for SUI and various acupuncture methods have been widely used in clinic. However, the comparative efficacy and safety of these acupuncture methods remains unclear. Clinicians are confused to select the optimal way to treat SUI. This review aims to gather solid evidence in order to provide reliable reference in establishing guidelines for acupuncture treatment of SUI. Method(s):Relevant databases including MEDLINE, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, the Chongqing VIP Chinese Science and Technology Periodical Database will be retrieved from their inception to April 2020. The quality of the included studies will be evaluated by the risk of bias tool and the evidence will be evaluated by Grading of Recommendations Assessment, Development and Evaluation System. Network meta-analysis will be conducted by using software R3.5.1. The primary outcome is the number of patients with self-reported continence and number of patients with self-reported improvement in SUI. Result(s):The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion(s):the results may be useful for patients, clinicians, and guideline-makers to choose the optimal acupuncture method for SUI treatment.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Yang, L., et al. (2023). "针灸联合克罗米芬、克罗米芬治疗多囊卵巢综合征患者排卵诱导效果及妊娠结局的Meta分析."
	Review question Using the method of reticular meta-analysis to study the ovulation promoting effect of clomiphene combined with acupuncture and moxibustion and clomiphene on patients with polycystic ovary syndrome (PCOS), the occurrence of follicle hyperstimulation syndrome, and Unruptured Follicles Occurrence of Luteinization Syndrome and the impact of pregnancy outcomes. Searches Search from the data of Cochrane Library、PubMed、Embase、Web of Science、CNKI、VIP、CBM, Chinese and English literature from the establishment of the database to the present. Types of study to be included Clinical Randomized Controlled Trials (RCT) Condition or domain being studied PCOS is a common cause of anovulatory infertility, and clomiphene is a first-line ovulation promoting drug for PCOS. However, it has problems such as low implantation rate and induction of follicle hyperstimulation syndrome and luteinized unruptured follicle syndrome. Acupuncture and moxibustion is becoming more and more popular in the world as a supplementary and alternative therapy for infertility. Participants/population Inclusion criteria: Research subjects: PCOS patients (age ≥ 18 years old); Exclusion criteria: Combined with other diseases such as hyperprolactinemia, thyroid dysfunction, premature ovarian failure, adrenal and ovarian tumors that secrete androgens, as well as hyperandrogenism caused by pituitary or hypothalamic amenorrhea, menstrual disorders, and ovulation disorders. Intervention(s), exposure(s) The intervention measures were clomiphene plus acupuncture and moxibustion, or acupuncture and moxibustion alone. Comparator(s)/control Clomiphene monotherapy or placebo Main outcome(s) In recent years, acupuncture and moxibustion combined with clomiphene has been increasingly used in the clinical research of PCOS. Therefore, this study uses the method of mesh meta-analysis to discuss the effect of clomiphene combined with acupuncture and moxibustion or clomiphene intervention on improving ovulation induction and pregnancy outcomes in PCOS patients, so as to provide evidence-based evidence for clinical use. Measures of effect Ratio of ovulation rate, pregnancy rate Additional outcome(s) [1 change] Is it accompanied by adverse ovulation outcomes，Frequency of acupuncture and moxibustion treatment，Regulation of LH, FSH, and T hormones. Measures of effect follicle hyperstimulation syndrome, and adverse reactions Data extraction (selection and coding) According to the inclusion and exclusion criteria of the study, two researchers conducted a preliminary screening of the retrieved literature based on the title and abstract. After reading the entire text, the final included literature was determined, the extracted content was determined, and a formal table was established. Any dissenting literature was negotiated with a third researcher. The researcher extracted the following data according to the table: (1) Basic information of the included study, including the lead author, publication time, publication country, BMI, etc; (2) Baseline characteristics of the study subjects, including each group's Sample size, age, etc; (3) Intervention measures: clomiphene+acupuncture and moxibustion, clomiphene, acupuncture and moxibustion; (4) Key elements of bias risk assessment; (5) Outcome indicators of concern. Risk of bias (quality) assessment Adopting the Cochrane Handbook recommended by the Cochrane Collaboration Network.The risk assessment tool for literature bias in version 5.1.0 affects the inclusion of studies Conduct literature quality evaluation, including the generation, allocation and hiding of random sequence Blindness, integrity of outcome indicators, selective reporting, other sources of bias wait for six items. If the literature is completely consistent, bias may occur low ability, rated as A level; Partial compliance, with a moderate likelihood of bias degree, rated as B level; Completely inconsistent, with a high likelihood of bias occurring,It is level C. Strategy for data synthesis Using the mvmeta installation package and related commands in Stata13.0 Process the data and use network graph and meta-analysis graph (prediction) plot interval diagrams and validity order diagrams, etc., using cumulative sorting method The area under the rate chart (SUCRA) indicates that each intervention becomes optimal the possibility of intervention measures. The value of SUCRA is between 0 and 1between (0 ≤ SUCRA ≤ 1), when SUCRA is 0, prompt for dry the preventive measures are ineffective, and the closer SUCRA is to 1, the better the prompt effect.Sort the intervention measures based on the size of the SUCRA value.Due to the outcome indicators of pregnancy rate, ovulation rate, and miscarriage rate being counted data,Therefore, using OR and its 95% confidence interval (CI) as the effect Indicators. Analysis of subgroups or subsets (1) Intervention methods of acupuncture and moxibustion: simple acupuncture, acupuncture and moxibustion combined, electroacupuncture, acupuncture combined with electroacupuncture. (2) Time of acupuncture and moxibustion intervention: once a week is low frequency, and three times a week is high frequency. Treatment for less than or equal to 1 month is classified as short-term, and treatment for more than 1 month is classified as long-term. (3) Time of acupuncture and moxibustion combined with clomiphene intervention: once a week is low frequency, and three times a week is high frequency. Treatment for less than or equal to 1 month is classified as short-term, and treatment for more than 1 month is classified as long-term. Contact details for further information Yang Lijie 22611808@qq.com Organisational affiliation of the review Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Review team members and their organisational affiliations Miss Yang Lijie. Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Miss Sun MingHan. Sichuan Provincial People's Hospital Mr Luo Lingjie. Chengdu Wenjiang District People's Hospital Miss Yang Wanqiu. Chengdu University of Traditional Chinese Medicine Mr Zou Kun. Sichuan University West China Second Hospital Collaborators Miss Li Hongru. Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Miss Miao Runqing. Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Miss Chen Yajjie. Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Mr Pang Li. Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Type and method of review 系统评价 Anticipated or actual start date 15 May 2023 Anticipated completion date 06 July 2023 Funding sources/sponsors 1.The Sichuan Natural Science Foundation project is sourced from the Sichuan Provincial Department of Science and Technology, NO 2023NSFSC0698. 2. The popularization and application project of the Sichuan Provincial Cadre Health Research Project is sourced from the Sichuan Provincial Administration of Traditional Chinese Medicine, NO 2022-505. 3. The general project is sourced from the Sichuan Provincial Administration of Traditional Chinese Medicine, NO CKY2021121. 4. Sichuan Provincial Hospital of Traditional Chinese Medicine/Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, NSFC pre research project, NO 21YY06. Grant number(s) State the funder, grant or award number and the date of award 1.NO 2023NSFSC0698 2.NO 2022-505 3. NO CKY2021121 4.NO 21YY06 Conflicts of interest Language English Country 中国, China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Acupuncture Therapy; Clomiphene; Female; Humans; Luteinization; Moxibustion; Ovulation; Polycystic Ovary Syndrome; Pregnancy Date of registration in PROSPERO 17 June 2023 Date of first submission 06 June 2023 Stage of review at time of this submission Stage	Started	Completed Preliminary searches	Yes	Yes Piloting of the study selection process	Yes	Yes Formal screening of search results against eligibility criteria	Yes	Yes Data extraction	No	No Risk of bias (quality) assessment	No	No Data analysis	No	No Revision note

Yang, L., et al. (2023). "Meta analysis of ovulation induction effect and pregnancy outcome of acupuncture & moxibustion combined with clomiphene in patients with polycystic ovary syndrome." Frontiers in Endocrinology 14: 1261016.
	Objective: Using Mesh Meta Analysis to evaluate the efficacy of Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene for treating Polycystic Ovary Syndrome (PCOS), in order to provide evidence-based medical evidence for whether to recommend Acupuncture & Moxibustion or Combine western medicine to treat PCOS.; Methods: Eight databases including The Cochrane Library, Pubmed, Embase, Web of Science, CNKI, Wanfang Date, VIP and CBM were searched by computer. The included research period is from the establishment of the database to May 2023, which concerned with randomized controlled trials involving Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene on ovulation induction and pregnancy outcome in patients with PCOS. The duration of the research paper is from 2016 to 2023.The inclusion criteria refer to the Rotterdam standards issued by the European Center for Human Reproduction and Embryology and the American Society of Reproductive Medicine in January 2003, or the Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome by the Endocrinology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Simultaneously exclude related diseases, repetitive literature, as well as literature with incomplete abstract information and no original data provided. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias included in the study, using Stata17.0 software for a mesh meta-analysis.; Results: Six randomized controlled trials were included, covering 1410 PCOS patients. Three interventions included Acupuncture & Moxibustion, Clomiphene, Acupuncture & Moxibustion combined with Clomiphene. Mesh Meta Analysis showed that in terms of improving ovulation rate, there was no statistical difference between Acupuncture & Moxibustion (A), Clomiphene (B), Clomiphene combined with Acupuncture & Moxibustion (C) (P>0.05).Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=0.15,95% CI (-0.51,0.80)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.60,95% CI (0.97,2.23)], Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.45,95% CI (0.91,1.99)]. In terms of pregnancy outcome, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.80,95% CI (-1.84,0.23)], Acupuncture & Moxibustion (A) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=0.29,95% CI (-0.73,1.30)], and Clomiphene (B) versus Clomiphene combined with Acupuncture & Moxibustion (C) [MD=1.09,95% CI (0.39,1.79)], The order of pregnancy rate from high to low is Acupuncture & Moxibustion combined with Clomiphene (C), Acupuncture & Moxibustion (A), Clomiphene (C).In terms of influencing endometrial thickness, the difference between the three intervention methods was statistically significant (P<0.05). Acupuncture & Moxibustion (A) versus Clomiphene (B) [MD=-0.84,95% CI (-1.87,0.19)], Acupuncture & Moxibustion (A) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=0.26,95% CI (-1.01,1.53)], Clomiphene (B) versus Acupuncture & Moxibustion combined with Clomiphene (C) [MD=1.10,95% CI (0.36,1.84)], Acupuncture & Moxibustion combined with Clomiphene (C) has the best effect on improving endometrial thickness. In subgroup analysis, the effect of Acupuncture & Moxibustion treatment frequency on ovulation rate and pregnancy rate was not statistically significant. The combination of Acupuncture & Moxibustion, Electroacupuncture and warm Acupuncture & Moxibustion has no effect on the pregnancy rate, but the combination of Electroacupuncture and Clomiphene has the best effect on improving the ovulation rate. In the observation of adverse reactions, compared with clomiphene alone, Acupuncture & Moxibustion combined with Clomiphene can reduce the occurrence of Luteinized Unruptured Follicle Syndrome (LUFS) and Ovarian Hyperstimul tion Syndrome (OHSS), and reduce the occurrence of physical adverse reactions such as nausea, vomiting, headache and dermatitis.; Conclusion: Acupuncture & Moxibustion is effective in improving the ovulation promoting effect and pregnancy outcome of PCOS patients. The ovulation promoting effect of Acupuncture & Moxibustion or combined with Clomiphene is similar to that of Clomiphene alone, but Acupuncture & Moxibustion combined with Clomiphene has more advantages in improving the pregnancy rate of PCOS, and it also can reduce the adverse reactions of Clomiphene alone. Acupuncture & Moxibustion can be used as a recommended treatment for PCOS. More cases should also be included in the subgroup analysis to study the impact of Acupuncture & Moxibustion programs on clinical efficacy and further optimize the Acupuncture & Moxibustion treatment program.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier (CRD42023433057).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Yang, Yang, Sun, Luo, Li, Miao, Pang, Chen and Zou.)

Yang, M., et al. (2023). "Effects of vitamin D supplementation on ovulation and pregnancy in women with polycystic ovary syndrome: a systematic review and meta-analysis." Frontiers in Endocrinology 14: 1148556.
	Objective: To evaluate the effect of vitamin D supplementation on pregnancy and ovulation in patients with polycystic ovary syndrome.; Method: We searched Pubmed, Medline (via Ovid, 1974 to 2020), EMBASE (via Ovid, 1974 to 2020), Cochrane Central Register of Controlled Trials (via Ovid), Web of Science, CNKI, WangFang and the Vip database from inception until April 2021. Two researchers independently screened articles, collected data and evaluated the quality, with Review manager 5.3 for meta-analysis.; Results: Totally 20 randomized controlled studies with 1961 subjects were included. Meta analysis showed that pregnancy rate [RR=1.44 (1.28, 1.62), p<0.00,001], ovulation rate [RR=1.42 (1.14, 1.78), p=0.002] and matured oocytes rate [RR=1.08 (1.03, 1.13), p=0.002] of vitamin D supplementation group were significantly higher than those of control group. Meanwhile, early miscarriage rate [RR=0.44 (0.30, 0.66), p<0.00,001], androgen level [MD=-2.31 (-3.51, -1.11), p=0.0002], luteinizing hormone [MD=-1.47 (-2.57, -0.36), p=0.009], follicle stimulating hormone [MD=-0.15 (-0.24, -0.05), p=0.002], and premature delivery rate [RR=0.38, 95% CI (0.21, 0.70), p=0.002] were declined significantly than the controls. However, only one article suggested that the progesterone [MD=6.52 (4.52, 8.52), p<0.05] in the vitamin D intervention group was increased. There was no notable difference in the biochemical pregnancy rate [RR=0.95 (0.55, 1.63), p=0.84], gestational hypertension rate [RR=0.40, 95% CI (0.15, 1.11), p=0.08], gestational diabetes mellitus rate [RR=0.27, 95% CI (0.05, 1.39), p=0.11], fertilization rate [RR=1.05 (1.00, 1.10), p=0.04], cleavage rate [RR=1.03 (0.99, 1.06), p=0.17], high-quality embryo rate [RR=1.08 (0.98, 1.20), p=0.10], endometrial thickness [MD=0.10], 77 (-0.23, 1.77), p=0.13], estrogen level [MD=-0.34 (-1.55, 0.87), p=0.59], LH/FSH [MD=-0.14, 95% CI (-0.48, 0.20), p=1.00] and anti-Mullerian hormone [MD=-0.22 (-0.65, 0.21), p=0.32].; Conclusion: Vitamin D supplementation contribute to the higher pregnancy and ovulation rates, and lower androgen, LH, FSH and early miscarriage rates in women with PCOS, regardless of the use of ovulation induction drugs or assisted reproductive technologies. However, no significant improvement was observed in fertilization rate or cleavage rate. Due to the limitation in quality of involved studies, more high-quality RCTs are needed for further validation.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021250284.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Yang, Shen, Lu, Peng, Zhou, Xu and Zhang.)

Yang, N., et al. (2021). "Efficacy of acupuncture for urinary incontinence in middle-aged and elderly women: A systematic review and meta-analysis of randomized controlled trials." European Journal of Obstetrics and Gynecology and Reproductive Biology 257: 138-143.
	Objectives: Our aim was to generalize the available evidence and evaluate the effectiveness of acupuncture for urinary incontinence in middle-aged and elderly women. Method(s): Six databases including VIP, CNKI, Wan Fang, Web of Science, PubMed and The Cochrane Library were systematically searched to retrieve similar studies updated to December 2019 to gather RCTs regarding the effectiveness of acupuncture for middle-aged and elderly women with urinary incontinence. Two researchers independently performed the whole process of retrieving the studies, extracting the data and assessing the risk of bias of the included studies. The current meta-analysis was performed using RevMan 5.3 software. Result(s): A total of eight studies with 607 patients were included in the evaluation. The current meta-analysis showed that Compared with rehabilitation exercise or medication, acupuncture intervention significantly improved the clinical effectiveness (OR = 5.52, 95 % CI, 3.13-9.73), reduced the urine leakage in pad test (SMD = -2.67, 95 % CI, -4.05 to -1.29) and decrease the ICIQ-SF score (MD = -3.46, 95 % CI, -3.69 to -3.22). The results indicated that acupuncture intervention can help the patients alleviate the symptoms effectively. Conclusion(s): Based on this study, acupuncture intervention of stress urinary incontinence in middle-aged and elderly women can improve the clinical effectiveness, reduce the urine leakage in pad test and ICIQ-SF score. More high-quality studies with large sample size are required for further verification.Copyright © 2020 Elsevier B.V.

Yang, N. and F. Zhou (2023). "Comparison of the effects of laparoscopic and open hysterectomy on surgical site wound infections in patients with endometrial cancer: A meta-analysis." International wound journal.
	This meta-analysis aimed to compare laparoscopic hysterectomy (LH) and open hysterectomy (OH) in terms of surgical site wound infection, length of hospital stay, and postoperative complications in patients with endometrial cancer (EC). PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang databases were comprehensively searched for studies on OH and LH for EC published between 2008 and July 2023, in any language. The literature was screened according to the inclusion and exclusion criteria, and the quality of the included case-control studies was assessed using the Newcastle-Ottawa Scale. Data were collated and analysed using Stata 17.0 software. A total of 1245 articles were screened according to the search strategy, and ultimately 15 studies were included in this meta-analysis, with a total of 1606 patients with EC, of which 751 were treated with LH and 855 with OH. The results showed that the rate of postoperative wound infection was significantly higher (OR: 0.290; 95% CI: 0.169-0.496, p < 0.001), the length of hospital stay was significantly longer (SMD: -1.976, 95% CI: -2.669 to -1.283, p < 0.001), and the incidence of postoperative complications was significantly higher (OR: 0.366; 95% CI: 0.280-0.478, p < 0.001) in the OH group than in the LH group. This study showed that LH was superior to OH for the treatment of EC and is associated with a lower rate of wound infection, shorter length of hospitalisation, and a reduced risk of complications. Thus, our findings support the choice of LH over OH for EC. (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Yang, R., et al. (2021). "Comparison of the Long-Acting GnRH Agonist Follicular Protocol with the GnRH Antagonist Protocol in Women Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis." Advances in Therapy 38(5): 2027-2037.
	Introduction: To evaluate the effectiveness and safety of long-acting GnRH agonist follicular and GnRH antagonist protocols among women undergoing in vitro fertilization (IVF) using data published in both English-language and Chinese studies.; Methods: We systematically searched the PubMed, Embase, Cochrane, CNKI, and Wanfang databases up to March 2019 for studies comparing long-acting GnRH agonist follicular and GnRH antagonist protocols in women undergoing IVF. The primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and implantation rate; safety outcomes were ovarian hyperstimulation syndrome (OHSS) and miscarriage rate in fresh cycle. Statistical analysis was done using R software. The study protocol was registered with PROSPERO (CRD42019139396).; Results: In 11 studies that met the inclusion criteria, 1994 women belonged to the long-acting GnRH agonist follicular protocol group and 1678 to the GnRH antagonist protocol group. Live birth rate (relative risk (RR) 1.61; 95% confidence interval (CI) 1.27, 2.05; P < 0.001), clinical pregnancy rate (RR 1.44; 95% CI 1.32, 1.58; P < 0.001), and implantation rate (RR 1.58; 95% CI 1.44, 1.73; P = 0.001) were higher in the long-acting GnRH agonist follicular protocol compared with the antagonist protocol group. There was no difference in miscarriage rate (RR 0.98; 95% CI 0.58, 1.64; P = 0.98) between the long-acting GnRH agonist follicular and antagonist protocols. However, OHSS rate (RR 1.63; 95% CI 1.15, 2.32; P = 0.0058) was lower in the GnRH antagonist protocol compared to the long-acting GnRH agonist protocol group.; Conclusion: The long-acting GnRH agonist follicular protocol was beneficial in improving live birth rate, clinical pregnancy rate, and implantation rate whereas the incidence of OHSS was significantly lower in women undergoing the GnRH antagonist protocol.

Yang, R., et al. (2023). "A meta-analysis of the risk factors of surgical site infection after hysterectomy for endometrial cancer." International wound journal.
	Surgical Site Infection (SSI) is one of the common postoperative complications after hysterectomy for endometrial cancer (EC). Previous studies have investigated the risk factors for SSI in patients with EC. However, big differences in research results exist, and the correlation coefficients of different research results are quite different. A meta-analysis was conducted to examine the risk factors related to SSI in patients with EC. We searched English databases to collect case-control studies or cohort studies published before July 20, 2023, including PubMed, Web of Science, Embase and ScienceDirect. The risk of bias in the included studies was assessed via Newcastle-Ottawa Scale. The analysis was performed using RevMan 5.4.1 tool. A total of 6 articles (n = 3647) were selected in this meta-analysis. The following risk factors were presented to be significantly correlated with SSI in EC: laparotomy (OR = 2.66, 95% CI [1.57, 4.54]), postoperative blood sugar ≥10 mmol/L (OR = 4.38, 95% CI [2.83, 6.78]), Federation International of Gynaecology and Obstetrics (FIGO) stage-III or IV (OR = 2.27, 95% CI [1.49, 3.46]). The occurrence of SSI is influenced by a variety of factors. Thus, we should pay close attention to high-risk subjects and take crucial targeted interventions to lower the SSI risk after hysterectomy. Owing to the limited quality and quantity of the included studies, more rigorous studies with adequate sample sizes are needed to verify the conclusion. (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Yang, S. and M. C. Chang (2020). "Effect of Repetitive Transcranial Magnetic Stimulation on Pain Management: A Systematic Narrative Review." Front. Neurol. 11: 114.
	Recently, clinicians have been using repetitive transcranial magnetic stimulation (rTMS) for treating various pain conditions. This systematic narrative review aimed to examine the use and efficacy of rTMS for controlling various pain conditions. A PubMed search was conducted for articles that were published until June 7, 2019 and used rTMS for pain alleviation. The key search phrase for identifying potentially relevant articles was (repetitive transcranial magnetic stimulation AND pain). The following inclusion criteria were applied for article selection: (1) patients with pain, (2) rTMS was applied for pain management, and (3) follow-up evaluations were performed after rTMS stimulation to assess the reduction in pain. Review articles were excluded. Overall, 1,030 potentially relevant articles were identified. After reading the titles and abstracts and assessing eligibility based on the full-text articles, 106 publications were finally included in our analysis. Overall, our findings suggested that rTMS is beneficial for treating neuropathic pain of various origins, such as central pain, pain from peripheral nerve disorders, fibromyalgia, and migraine. Although data on the use of rTMS for orofacial pain, including trigeminal neuralgia, phantom pain, low back pain, myofascial pain syndrome, pelvic pain, and complex regional pain syndrome, were promising, there was insufficient evidence to determine the efficacy of rTMS for treating these conditions. Therefore, further studies are needed to validate the effects of rTMS on pain relief in these conditions. Overall, this review will help guide clinicians in making informed decisions regarding whether rTMS is an appropriate option for managing various pain conditions.

Yang, S., et al. (2021). "Efficacy of the delayed start antagonist protocol for controlled ovarian stimulation in Bologna poor ovarian responders: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 303(2): 347-362.
	Background: Patients with a poor ovarian response (POR) represent the most difficult group of population to deal with in the clinical fertility practice. Bologna criteria are the first uniform definition of POR. Choosing a suitable controlled ovarian stimulation (COS) protocol which could give adequate oocytes to maximize the chance of obtaining at least one euploid blastocyst is crucial in the management for such patients. The delayed start antagonist protocol is a novel COS protocol designed for POR patients, however, its real efficacy is controversial compared to conventional protocols. The present study aims to summarize all available studies on this topic and perform a meta-analysis to explore the real treatment effect of this novel protocol in terms of reproductive outcomes.; Study Design: PubMed, EMBASE, Google Scholar, and the Cochrane Library from database establishment to June 2019 were searched. Randomized controlled trials (RCTs), which compared delayed start antagonist protocol (Del) to conventional controlled ovarian stimulation (COS) protocols (Con) in terms of reproductive outcomes, were included. The RevMan 5.3 was used to perform statistical analysis. The primary outcomes were the cycle cancellation rate, the clinical pregnancy rate and the miscarriage rate.; Results: 5 RCTs yielding 514 patients were eligible, of which 5, 5, 4 studies were included in analyzing the cycle cancellation rate, the clinical pregnancy rate, and the miscarriage rate respectively. Synthesized data of meta-analysis showed: delayed start antagonist protocol introduced a lower risk of cycle cancellation [risk ratio (RR) = 0.63, 95% confidence interval (CI) (0.45, 0.90), P = 0.01; 5 RCTs, 514 women (Del:Con = 256:258); I 2 = 0%; with rates of 16.02% (Del) vs. 26.36% (Con)], an increased chance to get clinical pregnancy [RR = 2.30, 95% CI (1.38, 3.82), P = 0.001; 5 RCTs, 514 women (Del:Con = 256:258); I 2 = 0%; with rates of 16.80% (Del) vs. 7.36% (Con)], and a comparable miscarriage rate [RR = 0.55, 95% CI (0.24, 1.23), P = 0.15; 4 RCTs, 58 women (Del:Con = 41:17) I 2 = 17%; with rates of 19.51% (Del) vs. 35.29% (Con)] compared to conventional COS protocols.; Conclusions: Delayed start antagonist protocol was a potentially valuable alternation for poor ovarian responders. However, future RCTs with large sample size and more scientific design are needed to verify its validity and draw a sound conclusion.

Yang, S., et al. (2023). "Effect of Isoflavones on Blood Lipid Alterations in Postmenopausal Females: A Systematic Review and Meta-Analysis of Randomized Trials." Advances in nutrition (Bethesda, Md.) 14(6): 1633-1643.
	The effects of isoflavones on postmenopausal female's blood lipid profile have yielded conflicting results in previous studies. Further investigation is necessary to determine the potential benefits of isoflavone therapy in managing cardiovascular health in this population. This meta-analysis aimed to assess the effects of isoflavones on blood lipid concentrations in postmenopausal females. A comprehensive search was conducted in major databases for randomized controlled trials published between 2000 and 2023. Eighteen studies were included in the analysis, which examined the impact of isoflavone intake on blood lipids in postmenopausal females. Isoflavone consumption resulted in a significant reduction in triacylglycerol (TG) concentrations (-12.50 mg/dL; 95% CI: -23.09, -1.91) and a modest increase in high-density lipoprotein cholesterol (HDL cholesterol) concentrations (1.83 mg/dL; 95% CI: 0.03, 3.64). Subgroup analysis showed that isoflavones significantly decreased TG (-15.79 mg/dL; 95% CI: -28.36, -3.22) and increased HDL cholesterol (2.49 mg/dL; 95% CI: 1.80, 3.19) in postmenopausal females under 65 y old. No significant effects were observed in females over 65 y old. Both low (≤80 mg/d) and high (>80 mg/d) doses of isoflavones exhibited TG-lowering effects, whereas only the high dose increased HDL cholesterol. Longer treatment duration (≥24 wk) was associated with a significant reduction in TG, whereas HDL cholesterol improvement occurred during the early period (<24 wk) of supplementation. The consumption of isoflavones resulted in a significant reduction in TG concentrations and an increase in HDL cholesterol concentrations among postmenopausal females under 65 y of age. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Yang, X., et al. (2022). "The effectiveness of mindfulness-based stress reduction intervention on alleviating anxiety and depression in postoperative patients with cervical cancer: A protocol for systematic review and meta-analysis." Medicine 101(5): e28706.
	Background: Surgical treatment for cervical cancer, as a stressor, largely leads to strong psychological reactions to stress like anxiety and depression. Whether mindfulness-based stress reduction (MBSR) can alleviate anxiety and depression in patients after cervical cancer surgery is controversial. Therefore, we aim to perform a meta-analysis involving randomized controlled trials analyzing the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery, thus providing evidence-based medical evidences for nonpharmacological interventions.; Methods: Randomized controlled trials analyzing the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery will be searched in online databases, including Cochrane Central Register of Controlled Trials Repositories, PubMed, Embase, Web of Science, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Data. After screening eligible studies, we will perform a meta-analysis on the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery.; Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.; Conclusion: This study will provide reliable evidence-based evidences for the effects of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery.; Ethics and Dissemination: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.; Osf Registration Number: DOI 10.17605/OSF.IO/EXUM3.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Yang, X., et al. (2022). "The effectiveness of group-based pelvic floor muscle training in preventing and treating urinary incontinence for antenatal and postnatal women: a systematic review." International Urogynecology Journal 33(6): 1407-1420.
	Introduction and hypothesis: Urinary incontinence (UI) is prevalent in antenatal and postnatal women. Pelvic floor muscle training (PFMT) is the first-line treatment for UI. Group-based PFMT provides a way for professionals to deliver this intervention to more women who need to prevent and/or treat UI. This review aims to (1) assess the effectiveness of group-based PFMT in preventing and treating UI in antenatal and postnatal women and (2) explore the characteristics of group-based intervention and factors which had an impact on the success of group-based PFMT. Method(s): Randomized controlled trials (RCTs) were included in this review. A comprehensive search was conducted in PubMed, Embase, Medline, PsycINFO, Maternity and Infant Care Database, CINAHL, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database. The overall quality was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RCTs which included pregnant and/or postnatal women with or without UI investigating the effectiveness of group-based PFMT were included. Result(s): Five RCTs were included in this review. The overall quality of the results of the included studies was low. Delivering group-based PFMT during pregnancy significantly reduced the prevalence of UI in both the pregnant period [risk ratio (RR) = 0.67, 95% confidence interval (CI) 0.57 to 0.80, P < 0.00001] and the postnatal period [RR = 0.66, 95% CI 0.52 to 0.84, P = 0.0008]. Only one RCT delivered group-based PFMT during the postnatal period. Conclusion(s): Evidence of weak quality supports the effectiveness of undertaking group-based PFMT in pregnancy to prevent UI during pregnancy and the postnatal period. No evidence showed the effectiveness of undertaking group-based PFMT in the postnatal period.Copyright © 2021, The Author(s).

Yang, Y., et al. (2019). "Melatonin as Potential Targets for Delaying Ovarian Aging." Current drug targets 20(1): 16-28.
	In previous studies, oxidative stress damage has been solely considered to be the mechanism of ovarian aging, and several antioxidants have been used to delay ovarian aging. But recently, more reports have found that endoplasmic reticulum stress, autophagy, sirtuins, mitochondrial dysfunction, telomeres, gene mutation, premature ovarian failure, and polycystic ovary syndrome are all closely related to ovarian aging, and these factors all interact with oxidative stress. These novel insights on ovarian aging are summarized in this review. Furthermore, as a pleiotropic molecule, melatonin is an important antioxidant and used as drugs for several diseases treatment. Melatonin regulates not only oxidative stress, but also the various molecules, and normal and pathological processes interact with ovarian functions and aging. Hence, the mechanism of ovarian aging and the extensive role of melatonin in the ovarian aging process are described herein. This systematic review supply new insights into ovarian aging and the use of melatonin to delay its onset, further supply a novel drug of melatonin for ovarian aging treatment. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Yang, Z., et al. (2022). "The pharmacological mechanism of Chinese herbs effective in treating advanced ovarian cancer: Integrated meta-analysis and network pharmacology analysis." Frontiers in Pharmacology 13: 1040641.
	Background: Advanced ovarian cancer (AOC) develops rapidly, adding to difficulties in treatment. Traditional Chinese medicine (TCM) plays a significant role in the treatment of AOC, and so to explore the efficacy and safety of TCM in the treatment of AOC and its effective targets, we performed the following review. Methods: The major databases were searched for randomized controlled trials of TCM for the treatment of AOC. A meta-analysis of the efficacy of Chinese herbs on AOC was conducted using RevMan 5.4 software. Active compounds and target genes were acquired using the TCMSP database. The main targets of AOC were obtained through the GenCards, OMIM, TTD, and DrugBank databases. A protein-protein interaction network carried out on the STRING platform was used to select core genes. The Metascape platform was applied to achieve GO and KEGG enrichment analysis. Results: A total of 24 studies were included. Meta-analysis shows the TCM group improved the overall response rate (OR = 2.71; 95% CI = [2.14, 3.44], Z = 8.25, p < 0.00001), overall survival (OR = 2.93, 95% CI = [2.03, 4.24], Z = 5.72, p < 0.00001), and progression-free survival (OR = 5.36, 95% CI = [5.03, 5.69], Z = 31.88, p < 0.00001) of AOC patients, as well as reducing many adverse events. There were 120 compounds, 246 herb target genes, and 1503 disease targets extracted. The 10 most important components were quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, isorhamnetin, hederagenin, stigmasterol, luteolin, 7-O-methylisomucronulatol, and calycosin. The 20 core targets were TP53 , STAT3 , JUN , AKT1 , MAPK3 , RELA , MAPK1 , ESR1 , IL6 , FOS , MAPK14 , TNF , CDKN1A , RB1 , CCND1 , EGFR , STAT1 , MDM2 , MAPK8 , and CAV1 . KEGG enrichment analysis showed that there are many pathways directly related to different types of tumors, such as in pathway cancer and prostate cancer. Conclusion: Our article reveals TCM is effective and safe against AOC and that Chinese herbs exert effects on the disease through multi-target, multi-component, and multi-pathway mechanisms. Systematic Review Registration: (www.crd.york.ac.uk/PROSPERO/), identifier (CRD42022369731).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yang, Wang, Hong, Zhang, Yang, Xia and Yang.)

Yan-juan, S., et al. (2019). "Effects of Acupuncture Related Therapy on Ovulation Rate and Pregnancy Rate in Patients with Polycystic Ovarian Syndrome." 中国针灸 39(7): 792-798.
	Objective: Systematic evaluation of the effects of acupuncture related therapies on the safety and effectiveness of ovulation and pregnancy rates in patients with polycystic ovary syndrome (PCOS). Methods: Computer retrieval PubMed, Dutch Medical Documentation Database (EMBase), Cochrane Library, China Biomedical Documentation Database (CBM), China Full text of the national journal Database (CNKI), Wanfang Database and Vip (VIP) Database for randomized controlled trials (RCT) for acupuncture treatment PCOS, retrieval time limits are from the building of the library until January 8, 2018. A 13.0 and WinBugs 1.4.3 Software for data analysis. Results: A total of 39 RCTs, including 4605 PCOS patients involving acupuncture related therapies and their comprehensive therapies, were observed for short-term efficacy. were acreole burial line+drug combination therapies (93.3%), acupuncture + Chinese medicine (91.4 percent), acupuncture (74.5 percent), acupuncture (65.7 percent), acupuncture + ear crypt (61.9 percent), acupuncture + ear crypt (49.6 percent); acupuncture combination therapy is better than Western medicine, the top 6 treatment measures are acupuncture + ear (91.5 percent), Acupuncture + Chinese Medicine (86.9%), Acupuncture + Ear Crypt (81.1%) ), acupuncture line+drug combination therapy (69.4%), acupuncture combination therapy (66.1%), placebo+western medicine (58.7%). Conclusion: Combination therapy is superior to monotherapy and safety is superior to Western medicine therapy. Sex, the findings of this study also require a large number of well-designed, high-quality and well-methodological RCTs Purchase of proof.

Yanran, L. and X. Qinwen (2022). "Effect of Lavender Aromatherapy on Postpartum Depressive Mood: Systematic Review and Meta-analysis Based on Randomized Controlled Trials."
	Review question P:pregnant woman; I:lavender aromatherapy; C:routine nursing or placebo control; O:postpartum depression scale scores; S:randomized controlled trials Searches Database: PubMed、Web of Science、Embase、Ovid、Cochrane Library; Time: from the creation of the database to the present; Language: English Types of study to be included randomized controlled trials Condition or domain being studied Postpartum depression (PPD) is a common and severe psychiatric disorder that manifests as persistent postpartum depression and is associated with hormonal changes in the body after childbirth and postpartum stress. Postpartum depression has a significant negative impact on the mother and her offspring, especially in the context of the COVID-19 pandemic, which has increased the incidence of postpartum depression to 32.6%. Postpartum depression is a global public health problem that requires widespread attention and focus. Participants/population adult(age over 18 years old); pregnant women Intervention(s), exposure(s) lavender aromatherapy Comparator(s)/control routine nursing or placebo control Main outcome(s) postpartum depression scale scores at different time periods Measures of effect Continuous variables were analyzed using standardized mean differences Additional outcome(s) None Measures of effect None Data extraction (selection and coding) Screening articles based on inclusion and exclusion criteria; Literature screening was conducted independently by 2 researchers. In case of disagreement, it was discussed and determined by consultation of the 3rd researcher. Extracted information included first author, year of publication, country, type of study design, intervention modality, timing of intervention, sample size of intervention and control groups, depression assessment scales, and outcome indicators Risk of bias (quality) assessment The Cochrane Collaboration's tool for assessing risk of bias Strategy for data synthesis I² > 50% is generally considered to indicate the presence of significant heterogeneity and a random effects model is used; if I² ≤ 50%, we will use the fixed effects model to analysis; Review Manager 5.4 be used for data analysis and make the forest plot and funnel plot Analysis of subgroups or subsets Subgroup analysis according to timing of intervention and different time periods after delivery Contact details for further information Yanran Li 1803901569@qq.com Organisational affiliation of the review Nantong University Review team members and their organisational affiliations Miss Yanran Li. Nantong University Miss Qinwen Xu. Nantong University Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 21 December 2022 Anticipated completion date 30 June 2023 Funding sources/sponsors None Grant number(s) State the funder, grant or award number and the date of award None Conflicts of interest Language Chinese-Simplified, English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Aromatherapy; Depression; Depression, Postpartum; Female; Humans; Lavandula; Postpartum Period; Pregnancy; Pregnant Women; Randomized Controlled Trials as Topic Date of registration in PROSPERO 31 December 2022 Date of first submission 20 December 2022 Stage of review at time of this submission

Yao, G., et al. (2022). "Survival of Patients With Cervical Cancer Treated With Definitive Radiotherapy or Concurrent Chemoradiotherapy According to Histological Subtype: A Systematic Review and Meta-Analysis." Frontiers in Medicine 9: 843262.
	Background: Cervical cancer is a leading cause of morbidity and mortality for women worldwide. Different histopathological cervical cancer subtypes (i.e., adenocarcinoma/adenosquamous carcinoma, and squamous cell carcinoma) are all treated similarly with definitive radiotherapy or concurrent chemoradiotherapy, but studies have reported differing survival prognoses. In this review and meta-analysis, we compared the disease-free and overall survivals of patients with cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy according to the histopathological subtypes.; Objective: To compare the disease-free and overall survivals of patients with adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy.; Methods: We systematically searched the Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE academic databases following PRISMA guidelines. We identified publications to conduct a random-effects meta-analysis to evaluate the disease-free and overall survivals of patients with cervical adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma treated with definitive radiotherapy or concurrent chemoradiotherapy.; Results: From 963 studies, we found eight eligible ones with 13,859 patients with cervical cancer (mean age, 52.2 ± 7.9 years). Our meta-analysis revealed a poorer outcome of disease-free (hazard ratio, 1.51; 95% CI, 1.28-1.79) and overall (hazard ratio 1.41; 95% CI, 1.26-1.57) survivals for patients with adenocarcinoma/adenosquamous carcinoma undergoing definitive radiotherapy or concurrent chemoradiotherapy than for those with squamous cell carcinoma undergoing similar treatments. We also observed that larger tumor size and advanced tumor stage are also significant prognostic factors that adversely impact survival outcomes in cervical cancer patients undergoing definitive radiotherapy or concurrent chemoradiotherapy.; Conclusion: Our results show poor disease-free and overall survivals for patients with cervical cancer and adenocarcinoma/adenosquamous carcinoma than for those with squamous cell carcinoma after treatment with definitive radiotherapy or concurrent chemoradiotherapy. Our findings clarify the risks associated with the conventional management of cervical cancer according to the histological type.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yao, Qiu, Zhu and Wang.)

Yap, T. A., et al. (2024). "First-in-Human Study of the Ataxia Telangiectasia and Rad3-related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors." Clinical cancer research : an official journal of the American Association for Cancer Research.
	PURPOSE: Tuvusertib (M1774) is a potent, selective, orally administered ATR protein kinase inhibitor. This first-in-human study (NCT04170153) evaluated safety, tolerability, maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of tuvusertib monotherapy. PATIENTS AND METHODS: Ascending tuvusertib doses were evaluated in 55 patients with metastatic or locally advanced unresectable solid tumors. A safety monitoring committee determined dose escalation based on PK, PD, and safety data guided by a Bayesian 2-parameter logistic regression model. Molecular responses (MRs) were assessed in circulating tumor DNA samples. RESULT(S): Most common Grade >=3 treatment-emergent adverse events were anemia (36%), neutropenia and lymphopenia (both 7%). Eleven patients experienced dose-limiting toxicities, most commonly Grade 2 (n=2) or Grade 3 (n=8) anemia. No persistent effects on blood immune cell populations were observed. The RDE was 180mg tuvusertib QD, 2 weeks on/1 week off, which was better tolerated than the MTD (180mg QD continuously). Tuvusertib median time to peak plasma concentration ranged from 0.5-3.5h and mean elimination half-life from 1.2-5.6h. Exposure-related PD analysis suggested maximum target engagement at >=130mg tuvusertib QD. Tuvusertib induced frequent MRs in the predicted efficacious dose range, MRs were enriched in patients with radiological disease stabilization and complete MRs were detected for mutations in ARID1A, ATRX and DAXX. One patient with platinum- and PARP inhibitor-resistant BRCA wild-type ovarian cancer achieved an unconfirmed RECIST v1.1 partial response. CONCLUSION(S): Tuvusertib demonstrated manageable safety and exposure-related target engagement. Further clinical evaluation of tuvusertib is ongoing.

Yap Timothy, A., et al. (2023). "Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results." Nature medicine 29(6): 1400-1411.
	Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. Here we report the results from module 1 of an ongoing phase 1 trial of the ATRi camonsertib (RP-3500) in 120 patients with advanced solid tumors harboring LOF alterations in DDR genes, predicted by chemogenomic CRISPR screens to sensitize tumors to ATRi. Primary objectives were to determine safety and propose a recommended phase 2 dose (RP2D). Secondary objectives were to assess preliminary anti-tumor activity, to characterize camonsertib pharmacokinetics and relationship with pharmacodynamic biomarkers and to evaluate methods for detecting ATRi-sensitizing biomarkers. Camonsertib was well tolerated; anemia was the most common drug-related toxicity (32% grade 3). Preliminary RP2D was 160 mg weekly on days 1-3. Overall clinical response, clinical benefit and molecular response rates across tumor and molecular subtypes in patients who received biologically effective doses of camonsertib (>100 mg d -1 ) were 13% (13/99), 43% (43/99) and 43% (27/63), respectively. Clinical benefit was highest in ovarian cancer, in tumors with biallelic LOF alterations and in patients with molecular responses. ClinicalTrials.gov registration: NCT04497116 . (© 2023. The Author(s).)

Yardimci, A., et al. (2021). "Agomelatine, A Potential Multi-Target Treatment Alternative for Insomnia, Depression, and Osteoporosis in Postmenopausal Women: A Hypothetical Model." Frontiers in Psychiatry 12: 654616.
	Insomnia, which is associated with menopausal depression, is a common symptom of menopause. Both symptoms have a common etiology, and can affect each other significantly. Pharmacological interventions, including hypnotics and antidepressants, and non-pharmacological therapies are generally administered in clinical practice for insomnia treatment. As another menopausal disorder, osteoporosis is described as a disease of low bone mineral density (BMD), affecting nearly 200 million women worldwide. Postmenopausal osteoporosis is common among middle-aged women. Since postmenopausal osteoporosis mainly results from low estrogen levels, menopausal hormone therapy (HT) is considered the first-line option for the prevention of osteoporosis during the menopausal period. However, almost no study has evaluated novel treatments for the combined prevention of insomnia, depression, and osteoporosis. Hence, it is necessary to develop new multi-target strategies for the treatment of these disorders to improve the quality of life during this vulnerable period. Melatonin is the major regulator of sleep, and it has been suggested to be safe and effective for bone loss therapy by MT-2 receptor activity. As a result, we hypothesize that agomelatine, an MT-1 and MT-2 receptor agonist and 5-HT2C receptor antagonist, holds promise in the combined treatment of insomnia, depression, and osteoporosis in middle-aged women during menopause.© Copyright © 2021 Yardimci, Ozdede and Kelestimur.

Yasmin, D., et al. (2023). "The impact of single versus double blastocyst transfer on pregnancy outcomes: a systematic review and meta-analysis."
	
Yasukawa, M., et al. (2021). "Management of recurrent granulosa cell tumor of the ovary: Contemporary literature review and a proposal of hyperthermic intraperitoneal chemotherapy as novel therapeutic option." The Journal of Obstetrics and Gynaecology Research 47(1): 44-51.
	Granulosa cell tumors of the ovary (GCT) are the most common type of sex cord stromal tumors. Although most of patients are diagnosed at early stage and has favorable 5-year overall survival rate, 16-23% of GCT ultimately develop recurrent disease. Recurrences are characterized by disseminated peritoneal metastasis. The treatment options include systemic chemotherapy, secondary CRS or palliative localized radiation therapy have not yet standardized due to the rarity of disease. Aggressive CRS followed up by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to provide benefit in other peritoneal disease but limited data available for recurrent GCT. We have a case of recurrent Adult-type GCT (AGCT) who was treated with CRS followed by HIPEC with mitomycin C and doxorubicin. The patient has no evidence of recurrence for approximately 11 years. An electronic search of the PubMed database with the following search terms: GCT, HIPEC showed that there were total 21 patients with recurrent GCT treated in seven different studies and 13 of 21 (61.9%) patients had no evidence of disease during follow-up ranging from 6 to 100 months. Three patients (14.2%) died of the disease. Six studies used cisplatin for HIPEC. At least 76.2% (16 of 21, data not available for five patients) had complete cytoreduction with total 16 cases of perioperative complications but no perioperative mortality was observed. Although further investigation is needed, we propose that CRS and HIPEC can be an effective therapeutic option for recurrent GCT at experienced institutions.

Yavas, I., et al. (2022). "Pelvic floor muscle training on urinary incontinence and sexual function in people with multiple sclerosis: A systematic review." Multiple Sclerosis and Related Disorders 58: 103538.
	Objective: This systematic review evaluates and summarizes the effects of pelvic floor muscle training on urinary incontinence and sexual function in people with multiple sclerosis. Data sources: PubMed, Scopus, PEDro, CINAHL, Web of Science, and ULAKBIM databases with keywords multiple sclerosis, urinary incontinence, sexual function, and pelvic floor muscle training were screened for randomized controlled studies and clinical trials from the beginning until July 2020 (updated in August 2021). Review methods: Two authors independently made the study selection. Turkish and English publications were taken into consideration. The risk of bias for the included studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. The Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEXT) was used to assess the methodological quality of studies. Data extraction was performed by two researchers independently. Result(s): Initial search identified a total of 2831 studies, after removing duplicates, 2180 records were screened and 7 studies with 248 participants [mean age (years): 50.0 +/- 11.11 and range: 20-67; mean Expanded Disability Status Scale score: 4.2 +/- 1.64 and range: 1.5-7.5] met the inclusion criteria. Only one study included male people with multiple sclerosis. Five studies were judged as being of some concerns and two studies were judged as being of high risk of bias. The TESTEXT scores ranged from 5 to 9 out of 15. The outcome measures were the health-related quality of life (6 studies), severity of overactive bladder (5 studies), leakage episodes (4 studies), severity of urinary incontinence (3 studies), 24-h pad test (2 studies), pad usage, sexual function, and anxiety and depression (1 study). Significant improvements were observed in all specified outcome measures in the groups that received pelvic floor muscle training in majority of the studies. Conclusion(s): Current evidence suggests that pelvic floor muscle training seems to be an effective treatment modality for improving health-related quality of life and reducing the severity of urinary incontinence and overactive bladder symptoms in people with multiple sclerosis. It also can reduce leakage episodes, pad usage, anxiety, and depression and improve sexual function. However, it should be noted that all included studies had some concerns or a high risk of bias in at least one domain of risk of bias assessment, and most of the studies did not have high quality.Copyright © 2022 Elsevier B.V.

Yazdany, T., et al. (2020). "American urogynecologic society systematic review: The impact of weight loss intervention on lower urinary tract symptoms and urinary incontinence in overweight and obese women." Female Pelvic Medicine and Reconstructive Surgery 26(1): 16-29.
	Objective Obesity can contribute to urinary symptoms such as urgency, frequency, and incontinence. In addition to classic treatments, weight loss interventions offer a unique clinical opportunity to improve these symptoms. Study Design The American Urogynecologic Society Systematic Review Group conducted a review of articles on the impact of surgical and behavioral weight loss (BWL) interventions on urinary symptoms in overweight and obese women. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria. Results The review group identified 43 publications from 39 studies, including 10 reports that used data from 5 randomized trials. Overall, there is high-certainty evidence that BWL, such as diet and exercise, decreases the prevalence of stress urinary incontinence 15% to 18% and overall urinary incontinence (UI) by 12% to 17% at 1 to 2.9 years. The certainty of evidence on the long-term impact of these interventions was lower. The certainty of the evidence was moderate to low regarding the benefit of BWL on urgency UI and overactive bladder symptoms. No randomized trials evaluated the impact of surgical weight loss on urinary symptoms, and the certainty of evidence of other study types was very low. Conclusions There is high-certainty evidence that BWL results in modest improvements in stress and overall UI in overweight and obese women at 1 to 2.9 years after the intervention. Robust studies with low risk of bias are needed to assess whether these benefits are maintained over the long term and are associated with adverse events and to assess the impact of surgical weight loss interventions on urinary outcomes in overweight and obese women.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Ye, X. and T. Li (2024). "Effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer and atypical endometrial hyperplasia or endometrial intraepithelial neoplasia: a meta-analysis." Archives of Gynecology and Obstetrics 309(1): 259-268.
	Objective: This meta-analysis aimed to evaluate the effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer (EC), atypical endometrial hyperplasia (AEH), or endometrial intraepithelial neoplasia (EIN). Method(s): Studies on hysteroscopic surgery combined with progesterone therapy for patients with early-stage EC, AEH, or EIN were searched from Embase, Web of Science, PubMed, and Cochrane Library databases. The included studies contained one or more of the following outcome variables: pregnancy rate, live birth rate, complete response (CR) rate, and recurrence rate after conservative treatment. The meta-analysis was performed using Stata. Result(s): 13 pieces of literature containing 239 patients with EC and 199 patients with AEH/EIN were included. As per the results of meta-analysis, the pregnancy rates of EC patients and AEH/EIN patients were 49% (95% CI 33-65%) and 47% (95% CI 31-64%), respectively, and the live birth rates were 45% (95% CI 32-58%) and 44% (95% CI 34-54%), respectively. CR rates of EC patients and AEH/EIN patients were 90% (95% CI 85-94%) and 100% (95% CI 97-100%), respectively, and the disease recurrence rates were 17% (95% CI 8-28%) and 11% (95% CI 3-23%), respectively. Conclusion(s): Hysteroscopic surgery combined with progesterone was linked to an improved overall response rate, reduced disease recurrence rate, and increased pregnancy and live birth rates among patients with EC and AEH/EIN.Copyright © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Yea Ji, W., et al. (2021). "Chemoradiotherapy with hyperthermia versus chemoradiotherapy alone in locally advanced cervical cancer: a systematic review and meta-analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 38(1): 1333-1340.
	Purpose: Concurrent chemoradiotherapy (CCRT) is recommended as the standard treatment for locally advanced cervical cancer (LACC). However, the synergistic effect of hyperthermia (HT) with CCRT remains unclear. Therefore, we performed a meta-analysis to evaluate the effect of HT with CCRT on LACC patients.; Methods and Materials: A systematic literature search was conducted on the MEDLINE, PubMed, Embase, Cochrane library and SCOPUS databases for articles that compared CCRT with HT and CCRT alone as treatments for LACC. Hazard ratios (HRs) and risk ratios (RRs) were used to compare five-year overall survival (OS), local relapse-free survival (LRFS) and incidence of acute and chronic toxicity between the two treatments.; Results: Two articles out of 2860 were finally selected for analysis. A total of 536 patients were evaluated (CCRT with HT group: 268, CCRT group: 268). FIGO stages I-II and III-IV were found in 295 (55.0%) and 241 patients (45.0%), respectively. The CCRT with HT group had significantly better five-year OS than the CCRT group (HR 0.67, 95% confidence interval [CI] 0.47-0.96, p = 0.03). LRFS of patients was superior in the CCRT with HT group than in the CCRT group, but without significance (HR 0.74, 95% CI 0.49-1.12; p = 0.16). Moreover, there was no difference between the two groups regarding acute and chronic toxicity.; Conclusion: This systematic review and meta-analysis showed that CCRT with HT significantly improved OS in LACC patients without increasing acute and chronic toxicity. Therefore, tri-modality treatment could be a feasible approach for patients with LACC.

Yegya-Raman, N., et al. (2020). "Stereotactic body radiation therapy for oligometastatic gynecologic malignancies: A systematic review." Gynecologic Oncology 159(2): 573-580.
	Objective: To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) for oligometastatic gynecologic malignancies.; Method: A comprehensive search of the PubMed, Medline, and EMBASE databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. "Oligometastatic" was defined as a limited number of uncontrolled/untreated metastatic lesions (typically ≤ 5), including regional nodal metastases. Primary outcomes were response rate (complete response or partial response), local control of oligometastatic lesions, and toxicity.; Results: Of 716 screened records, 17 studies (13 full length articles, 4 conference abstracts) were selected and analyzed as 16 unique studies. A total of 667 patients were treated with ~1071 metastatic lesions identified. Primary sites included ovarian (57.6%), cervical (27.1%), uterine (11.1%), vaginal (0.4%), vulvar (0.3%), and other/unspecified (3.4%). Most patients (65.4%) presented with a single metastatic lesion. Metastatic lesion sites included the abdomen (44.2%), pelvis (18.8%), thorax (15.5%), neck (4.6%), central nervous system (4.3%), bone (1.6%), and other/unspecified (11%). Of the lesions, 64% were nodal. Response rate (among 8 studies) ranged from 49% to 97%, with 7/8 studies reporting > 75% response rate. Local control ranged from 71% to 100%, with 14/16 studies reporting ≥ 80% local control. No grade ≥ 3 toxicities were observed in 9/16 (56%) studies. Median progression-free survival (PFS) (among 10 studies) ranged from 3.3 months to 21.7 months. Disease progression most commonly occurred outside of the SBRT radiation field (79% to 100% of failures).; Conclusions: SBRT for oligometastatic gynecologic malignancies is associated with favorable response and local control rates but a high rate of out-of-field progression and heterogeneous PFS. Additional study into rational combinations of SBRT and systemic therapy appears warranted to further improve patient outcomes.; Competing Interests: Declaration of Competing Interest S.K. Jabbour has research funding from Merck and Nestle, outside of the submitted work. The remaining authors have nothing to disclose. (Copyright © 2020 Elsevier Inc. All rights reserved.)

Yenigul Nefise, N., et al. (2022). "The value of LH supplementation in young women with diminished ovarian reserve treated with GnRH Antagonist Protocol for ovarian hyperstimulation in ICSI-cycles." Ginekologia polska.
	Objectives: To compare the success of two controlled ovarian hyperstimulation protocols; rFSH + hp-hMG with only rFSH in the GnRH antagonist protocol in diminished ovarian reserve under 35 years of age.; Material and Methods: Data from January 2015 to June 2019 were abstracted from the hospital records of IVF Clinic. The women younger than 35 years of age who were diagnosed as diminished ovarian reserve and underwent standard GnRH antagonist protocol were included. Patients in Group-1 underwent controlled ovarian stimulation with rFSH alone and Group-2 with rFSH in combination with hp-hMG. Patients in both groups were divided into three subgroups according to their antral follicle count at Day 3: < 4 (a), 4-6 (b), and 7-10 (c). Demographic features and IVF outcomes of the patients were extracted.; Results: Total number of retrieved oocytes, was higher in Group-1 than Group-2 (6.5 ± 2.1 vs 5.5 ± 2.3, respectively, p < 0.001). However, there were no significant differences between the two groups in terms of clinical pregnancy rate, implantation rate, miscarriage rate and live birth rate. Although the main study outcome parameters did not show significant difference between Group-1a and Group-2a, the number of mature oocytes (5 ± 2.8 vs 1.8 ± 1.2, respectively, p = 0.006) was higher in Group-1a.; Conclusions: We observed no beneficial effect of LH supplementation during IVF for the treatment of women under 35 years old with diminished ovarian reserve in the first treatment cycle when compared with rFSH only in the antagonist protocols.

Yenigül Nefise, N., et al. (2023). "Does the decrease in E2 levels between the trigger of ovulation and embryo transfer affect the reproductive outcome in IVF-ICSI cycles?" Turkish Journal of Obstetrics and Gynecology 20(3): 199-205.
	Objective: This study aimed to evaluate the effect of the rate of decline in serum estradiol (E2) levels between hCG injection and the day of embryo transfer (ET) on the success of assisted reproductive technology (ART) in women with infertility of different etiologies.; Materials and Methods: Women 20-45 years of age who underwent a standard GnRH antagonist or long agonist protocol and fresh ET during day 3 of their first ART cycle were included. Group 1 was diagnosed with low ovarian reserve, group 2 comprised high ovarian responders, and group 3 consisted of normal responders. Both groups were divided into four subgroups according to the decrease in E2 levels between the day of hCG injection and the day of ET. Subgroup A patients had a decrease of <20%, subgroup B a decrease of 20-40%, subgroup C a decrease of 41-60%, and subgroup D a decrease >60%. The primary outcome measure was the effect of an E2 decline, based on the measurement of E2 on the day of hCG administration and day of ET, on the implantation rate. The secondary outcome was the change in E2 values in these three groups.; Results: The study was conducted on 1.928 women. Of these, 639 were poor responders (group 1), 502 were high responders (group 2), and 787 women had a normal ovarian response (group 3). Patients with a 60% decrease in their E2 levels on the ET day after hCG had a lower live birth rate (LBR) and higher miscarriage rate (MCR), except normoresponders, in whom a similar decline was significant only with respect to MCR.; Conclusion: We indicate that high ovarian responders who underwent fresh ET cycles with a 60% decrease in their E2 levels on the ET day after human chorionic gonadotropin had lower LBRs and higher miscarriage. However, in normoresponder women, this decline was only significant in miscarriage.

Yeoh Su, A., et al. (2024). "Psychosocial interventions for ovarian cancer survivors: A systematic review." Psycho-Oncology 33(1): e6280.
	Objectives: Ovarian cancer survivorship is complex and is associated with greater symptom burden, fear of reoccurrence, sexual dysfunction, lower quality of life and heightened existential distress in contrast to other cancers. This systematic review aimed to investigate the effectiveness for, and perspective of, psychosocial interventions encompassing psychological, social, and emotional support, tailored to, or involving ovarian cancer survivors at all stages of disease.; Methods: Adhering to the PRISMA-SR statement guidelines, a systematic search was conducted across PsycINFO, MEDLINE, Embase, Emcare, CINAHL, Scopus, Cochrane Library databases, Google, and Google Scholar. Two reviewers independently undertook a two-stage screening process. The Mixed Methods Appraisal Tool was utilised to assess the methodological quality of included studies. Data were extracted using customised data extraction tools and narratively synthesised.; Results: Thirteen studies were included in this review. Generally positive effects of psychosocial interventions were observed across a range of outcome domains (meaning enhancing, cognitive, social, emotional, and cancer-specific). However, the characteristics of interventions and outcome measures varied across studies. Psychoeducational interventions were identified as the most common psychosocial approach, while Acceptance and Commitment Therapy showed promise in addressing the disease's high symptom burden. Women's perspectives of psychosocial interventions were described as "useful" and promoted positive self-regard.; Conclusion: While the evidence base largely support positive effects of psychosocial interventions for ovarian cancer survivors, this finding is constrained by heterogeneity of interventions and modest gains. Future research may explore the standardisation of psychosocial interventions for this demographic, investigating its effects on less explored but prevalent concerns among ovarian cancer survivors such as fear of cancer recurrence and sexual dysfunction. (© 2024 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Yerezhepbayeva, M., et al. (2022). "Comparison of two invasive non-surgical treatment options for uterine myomas: uterine artery embolization and magnetic resonance guided high intensity focused ultrasound-systematic review." BMC Women's Health 22(1): 55.
	Background: Uterine Artery Embolization (UAE) and Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) are two noninvasive treatments for uterine leiomyoma.; Methods: This systematic review, following PRISMA guidelines, analyzed the effectiveness of two treatments by comparing percent fibroid volume shrinkage immediately after the procedure and after 3, 6, 12 and 24 months of follow-up and also assessed and compared common complications following treatment. The search utilized Science Direct, PubMed, MEDLINE, Google Scholar and BioMed Central databases, selecting manuscripts published during the period 2000 and 2020. Studies with premenopausal patients with previous treatments for uterine leiomyoma and/or with other pelvic diseases were excluded.; Results: Twenty-nine papers satisfied inclusion and exclusion criteria. Results were pooled and stratified by treatment and follow-up time. Weighted fibroid volume percent shrinkage after UAE was statistically significantly greater than MRgHIFU at 6, 12, and 24 months follow-up times. However, UAE had statistically significantly more complications, such as pain, nausea and vomiting. However, this study cannot conclude that UAE is more effective than MRgHIFU due to confounding factors. (© 2022. The Author(s).)

Yetişkin, G., et al. (2022). "The effect of pelvic floor muscle exercises applied during pregnancy on genito-pelvic pain level in postpartum period." International Urogynecology Journal 33(10): 2791-2799.
	Introduction and Hypothesis: The goal of the study is to determine the effect of pelvic floor muscle exercises on genito-pelvic pain levels during the postpartum period.; Methods: The data of the study, which was carried out in a randomized controlled experimental design, were collected in the antenatal policlinic of a public hospital from June-December 2019. There were 60 pregnant women in the experimental and control groups. Pelvic floor muscle exercises were applied to the pregnant women in the experimental group from the 30th week of gestation to the 6th week postpartum. The control group was not given pelvic floor muscle exercise training, and only data collection forms were filled in. During the study, the Descriptive Form, Verbal Category Scale, Pelvic Floor Distress Inventory-20, and Labour and Postpartum Information Form were given to the pregnant women in both groups.; Results: After pregnant women in the experimental group performed pelvic floor muscle exercises, pain levels were significantly lower than in the control group (p < 0.01). Pelvic Floor Distress Inventory-20 total score and sub-dimension scores of the experimental group were statistically significantly lower than in the control group (p < 0.01). In addition, a statistically significant difference was found (p < 0.01) in the postpartum 72 h findings of the experimental group in which pelvic floor muscle exercises were applied compared to the control group.; Conclusions: According to the result of the study, as the gestational weeks progress, the genito-pelvic pain increases. Pelvic floor muscle exercises applied during pregnancy prevent the development and progression of pelvic floor disorders in both the antenatal and postnatal periods.; Trial Registration: NCT05343520. (© 2022. The International Urogynecological Association.)

Yeung Anamaria, R., et al. (2022). "Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 40(27): 3115-3119.
	Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival ( P = .53), disease-free survival ( P = .21), or locoregional failure ( P = .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT v 15.1% CRT, P = .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT v 8.6% CRT, P = .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT v -6.0, standard deviation = 14.3, CRT, P = .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.

Yfantopoulos, N., et al. (2023). "Cost Effectiveness Analysis of Pembrolizumab as First-Line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer in Greece." Value in Health 26(12 Supplement): S62.
	Objectives: In 2020, the World Health Assembly announced a global comprehensive plan to eliminate cervical cancer, involving vaccination, screening, and treatment-rate targets. Pembrolizumab in combination with - paclitaxel, cisplatin, carboplatin, and bevacizumab - is reimbursed for first-line treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS>=1) based on the results of KEYNOTE-826 trial. The present study aims to assess cost-effectiveness of Pembrolizumab plus SoC versus SoC alone in Greece in this setting. Method(s): A semi-Markov State Transition model with three health states (progression-free, progressed disease and death) was adapted to Greece, adopting payer's perspective with a 40 years' time-horizon. Clinical, safety and quality of life data were drawn from KEYNOTE-826 trial (22 months follow-up data). Primary outcomes were patients' life years gained (LYg), quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICER) per QALY. Both costs and QALYs were discounted at 3.0% per annum. A one-way sensitivity analysis (OWSA) was undertaken to examine the most influential parameters on the results and a probabilistic sensitivity analysis (PSA) was conducted to account for uncertainty in the model. Result(s): The model showed that, over a lifetime horizon, total average cost per patient with pembrolizumab plus SoC was estimated at 157,368 whereas the cost of SoC alone was 73,360. Pembrolizumab with SoC was more effective than SoC providing 6.104 LYs versus 2.991 LYg which translated into 3.412 and 1.799 QALYs respectively; overall incremental LYG were 3.113 and the incremental QALYs were 1.613. The ICER was estimated at 52,081/QALY which is below the national cost-effectiveness threshold for Greece(3x GDP capita, 52,770/QALY). The OWSA and PSA results confirmed the robustness of the model. Conclusion(s): The present modeling study suggests that pembrolizumab in combination with SoC is a cost-effective intervention compared to SoC that improves health outcomes and the efficient allocation of resources in Greece.Copyright © 2023

Yi, L., et al. (2021). "Safety and efficacy of compounded bioidentical hormone therapy in perimenopausal and postmenopausal women: a systematic review and meta-analysis of randomized controlled trials."
	
Yi, L., et al. (2024). "Acupuncture therapies for relieving pain in pelvic inflammatory disease: A systematic review and meta-analysis." PloS One 19(1): e0292166.
	BACKGROUND: Studies investigating the effectiveness of acupuncture therapies in alleviating pain in pelvic inflammatory disease (PID) have gained increasing attention. However, to date, there have been no systematic reviews and meta-analyses providing high-quality evidence regarding the efficacy and safety of acupuncture therapies in this context. OBJECTIVE: The objective of this review was to assess the efficacy and safety of acupuncture therapies as complementary or alternative treatments for pain relief in patients with PID. METHOD: A comprehensive search was conducted in eight databases from inception to February 20, 2023: PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database. Randomized controlled trials (RCTs) investigating acupuncture therapies as complementary or additional treatments to routine care were identified. Primary outcomes were pain intensity scores for abdominal or lumbosacral pain. The Cochrane risk of bias criteria was applied to assess the methodological quality of the included trials. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence. Data processing was performed using RevMan 5.4. RESULT: This systematic review included twelve trials comprising a total of 1,165 patients. Among these, nine trials examined acupuncture therapies as adjunctive therapy, while the remaining three did not. Meta-analyses demonstrated that acupuncture therapies, whether used alone or in combination with routine treatment, exhibited greater efficacy in relieving abdominal pain compared to routine treatment alone immediately after the intervention (MD: -1.32; 95% CI: -1.60 to -1.05; P < 0.00001). The advantage of acupuncture therapies alone persisted for up to one month after the treatment (MD: -1.44; 95% CI: -2.15 to -0.72; P < 0.0001). Additionally, acupuncture therapies combined with routine treatment had a more pronounced effect in relieving lumbosacral pain after the intervention (MD: -1.14; 95% CI: -2.12 to -0.17; P < 0.00001) in patients with PID. The incidence of adverse events did not increase with the addition of acupuncture therapies (OR: 0.56; 95% CI: 0.21 to 1.51; P = 0.25). The findings also indicated that acupuncture therapies, as a complementary treatment, could induce anti-inflammatory cytokines, reduce pro-inflammatory cytokines, alleviate anxiety, and improve the quality of life in patients with PID. CONCLUSION: Our findings suggest that acupuncture therapies may effectively reduce pain intensity in the abdomen and lumbosacral region as complementary or alternative treatments, induce anti-inflammatory cytokines, decrease pro-inflammatory cytokines, alleviate anxiety, and enhance the quality of life in patients with PID, without increasing the occurrence of adverse events. However, due to the low quality of the included trials, the conclusion should be interpreted with caution, highlighting the need for further high-quality trials to establish more reliable conclusions.

Yi, T., et al. (2023). "Transdermal estrogen gel vs oral estrogen after hysteroscopy for intrauterine adhesion separation: A prospective randomized study." Frontiers in Endocrinology 14: 1066210.
	Background: This randomized controlled trial (RCT) aimed to compare two different routes of postoperative estrogen treatment on the improvements of menstruation, postoperative endometrial thickness, and fertility outcomes in patients with moderate to severe intrauterine adhesions (IUA).; Methods: This study prospectively included 78 women (age: 25 to 45 years) with moderate to severe IUA who underwent hysteroscopic resection of adhesions between March 2019 and October 2020. The enrolled patients were randomized 1:1 into either the transdermal gel group (n = 39) or the estradiol valerate oral tablet group (n = 39) on the day of receiving hysteroscopy. Postoperative endometrial thickness, AFS (American Fertility Society) score, estrogen level, and the pattern and amount of menstruation were compared. Pregnancy information was actively collected during 1-year follow-up after the operation.; Results: The postoperative endometrium thickness was improved in both groups, and both groups gained menstruation improvement rates of 67%. For patients who underwent second-look hysteroscopy (17 from the oral group and 19 from the transdermal group), the mean AFS score declined greater than 2 in both groups. For patients with postoperative pregnancy intention, the pregnancy rates at 1-year follow-up after the procedures were 40.5% and 28% in the transdermal group and oral group, respectively. Although no statistically significant difference was observed between the two groups, patients in the transdermal group had a tendency toward increased pregnancy rate.; Conclusions: Transdermal administration of estrogen is equally efficacious as oral estrogen in postoperative treatment of IUA patients with a relatively safe profile. It is very likely to broaden its indication to the field of IUA.; Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=37197, identifier ChiCTR1900022110.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Yi, Zhang, Gupta, Li and Zhong.)

Yi, X. Y., et al. (2021). "Genistein for glycolipid metabolism in postmenopausal women: a meta-analysis." Climacteric : the journal of the International Menopause Society 24(3): 267-274.
	Objective: This study aimed to evaluate the effects of genistein on glycolipid metabolism in postmenopausal women.; Methods: Electronic databases were searched and relevant reports were hand-screened. We included only randomized controlled trials of isolated genistein for glycolipid metabolism. The primary outcome for lipid metabolism included a changed value of low-density lipoprotein cholesterol (LDL-C), and for glucose metabolism was a changed value of homeostasis model assessment for insulin resistance (HOMA-IR). Secondary outcomes included a changed value of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), fasting blood insulin (INS), and body mass index (BMI).; Results: Ten trials with 11 articles were included. The level of LDL-C was not decreased in the genistein group compared with the placebo group (standardized mean difference [SMD] = -0.58; 95% confidence interval [CI] - 1.19, 0.02; p = 0.06). No statistical significance was found in subgroup analyses. HOMA-IR was obviously improved in the genistein group with SMD of -0.51 (95% CI -0.88, -0.14; p = 0.006). In subgroup analyses, HOMA-IR was improved more in women with BMI <30 kg/m 2 and without metabolic disorders ( p < 0.0001). For secondary outcomes, there were significant differences in total cholesterol, HDL-C, FBG, and INS, but not triglyceride or BMI.; Conclusions: Genistein was effective in ameliorating glycolipid metabolism by increasing HDL-C levels and decreasing total cholesterol levels and improving insulin sensitivity.

Yi, Y., et al. (2022). "Comparison of the fertility results and cancer outcomes of early-stage cervical cancer between open and minimally invasive radical trachelectomy: a meta-analysis."
	
Yichen, X., et al. (2021). "The efficacy and safety of simple-needling for the treatment of primary dysmenorrhea compared with ibuprofen: a systematic review and meta-analysis."
	
YiFan, K. and W. Zhihong (2022). "Impact of local endometrial injury on reproductive outcome in patients: A systematic review and meta-analysis."
	
Yi-Fan, L., et al. (2020). "A systematic review and meta-analysis on the effects of metformin on survival outcomes and risk in women with cervical cancer." Eur. J. Gynaecol. Oncol. 41(4): 504-507.
	
Yi-fen, C. and C. Yi-Chun (2023). "Effect of Vit. D Supplementation on Primary Dysmenorrhea; A Systematic Review and Meta-Analysis of Randomized Clinical Trials."
	
Yildiz, E., et al. (2023). "Does Mesh Application by Using Inside-Out and Outside-In Techniques during Transobturator Tape Surgery Change the Success?" Duzce medical journal 25(1): 56‐61.
	Aim: This study aimed to evaluate the effect of transobturator tape (TOT) surgery, which is performed in the treatment of stress urinary incontinence (SUI) in women, using the inside‐out or outside‐in technique on the success of the surgery. Material and Methods: Sixty‐five women diagnosed with SUI and for whom it was decided to perform TOT surgery were included in this prospective randomized study. Participants were divided into two groups, 32 women underwent TOT surgery using the inside‐out technique and 33 women underwent TOT surgery using the outside‐in technique. The surgical data of patients, the 3‐month incidence of complications, pre‐, and postoperative scores of the incontinence impact questionnaire (IIQ‐7), and the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF) were recorded. Objective, subjective, and inadequate treatment rates were determined for the evaluation of the success of the treatment. Results: When the two groups were compared, there was no statistically significant difference in terms of age, body mass index, parity, menopause status, duration of incontinence, and preoperative IIQ‐7 and ICIQ‐SF scores. There were no statistically significant differences between surgical durations, length of hospital stay, early surgical complications, and postoperative 3rd month IIQ‐7 and ICIQ‐SF scores. There were no statistically significant differences between the two groups in terms of objective, subjective, and inadequate treatment rates. Conclusion: TOT surgery is successful with both techniques in patients with SUI. Choosing the technique with which the surgeon is experienced and feels most confident will increase the success of TOT surgery regardless of the technique.

Yildiz, G., et al. (2021). "The effect of local endometrial injury on the success of intrauterine insemination." Journal of Experimental and Clinical Medicine (Turkey) 38(4): 521‐524.
	To determine the effect of local endometrial injury on implantation success in patients diagnosed with unexplained infertility and undergoing intrauterine insemination (IUI) after ovulation induction with gonadotropins. In this prospective randomized controlled trial, 82 infertile patients underwent IUI following ovulation induction with gonadotropin. In the study group (n:40), local endometrial injury (stratch) was performed to the posterior side of the endometrial cavity with a biopsy catheter between the 21‐26th days of luteal phase of the cycle preceding ovarian stimulation. There was no statistically significant difference between the study and the control groups in terms of age of female, age of male, duration of infertility, BMI, serum FSH and LH levels, mean dose of gonadotropin and mean duration of ovulation induction (p>0.05). Clinical pregnancy was achieved in two patients (4.76%) in control group and four (10%) patients in the study group, with no significant difference between groups (p=0.18). All pregnancies achieved in the control and the study groups passed 12th gestational weeks and continued. Ectopic pregnancy, multiple pregnancy and abortion was not observed in any patient in both groups. In the study group, pain level immediately after endometrial biopsy procedure was evaluated with visual analog scale (VAS) and it was established that only one (2.5%) patient experienced severe pain after the procedure. Although local endometrial damage in the menstural period before ovulation induction and IUI cycle increases clinical pregnancy rates in the infertile patients, this increase is not statistically significant. Multi‐center randomized controlled studies are needed for local endometrial damage to be recommended routinely in clinical practice.

Yildiz Gunes, O., et al. (2022). "Perioperative goal-directed fluid management using noninvasive hemodynamic monitoring in gynecologic oncology." Brazilian journal of anesthesiology (Elsevier) 72(3): 322-330.
	Background: Intraoperative fluid management is important for the prevention of perioperative morbidity and mortality. Our study aimed to investigate the perioperative feasibility and benefits of Goal-Directed Fluid Management (GDFM) using noninvasive hemodynamic monitoring in gynecologic oncology patients with acute blood loss and severe fluid loss. We assessed the effects of GDFM on hemodynamics, organ perfusion, complications, and mortality outcomes.; Methods: This randomized prospective study included 104 patients over the age of 18 years, including 56 patients with endometrial cancer and 48 patients with ovarian cancer who had open surgery. The anesthetic approach was standardized for all patients. We compared the perioperative results of the subjects who were randomized into GDFM (n = 51) and Liberal Fluid Management (LFM) (n = 53) groups using a computer program.; Results: The median perioperative crystalloid replacement (2000 vs. 2700; p < 0.001) and total volume of fluid (2260 vs. 3200; p < 0.001) were lower in the GDFM group compared to the LFM group. The hemodynamic findings and the HCO 3 and lactate levels of the GDFM group did not significantly change perioperatively. The heart rate, mean arterial pressure, and HCO 3 levels of the LFM group decreased and serum lactate levels increased perioperatively. The hospitalization rate in ICU (7.8% vs. 28.3%; p = 0.010), rate of patients with comorbidity conditions indicated in ICU (2% vs. 17%; p = 0.024), and rate of complications (17.6% vs. 35.8%; p = 0.047) were lower in the GDFM group compared to the LFM group.; Conclusion: The amount of intraoperatively administered crystalloid solution and complication rates were significantly lower in gynecologic oncologic surgery patients who received GDFM. Besides, hemodynamic findings, and lactate levels of the GDFM group did not change significantly during the perioperative period.; Competing Interests: Conflicts of interest The authors declare no conflicts of interest. (Copyright © 2022 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Yildiz, N., et al. (2022). "Efficacy of intravaginal electrical stimulation with different treatment frequency in women with refractory idiopathic overactive bladder." International braz j urol 48(4): 662-671.
	Objective: The aim of this study is to evaluate the effect of intravaginal electrical stimulation (IVES) therapies with different treatment frequencies (two or five days in a week) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with refractory idiopathic overactive bladder (OAB). Material(s) and Method(s): Fifty-two women with refractory idiopathic OAB were randomized into two groups as follows: Group 1 (n:26) received BT and IVES, two times in a week, for 10 weeks and Group 2 (n:26) received BT and IVES five times in a week, for 4 weeks. IVES was performed 20 minutes in a day, a total of 20 sessions for both groups. Women were evaluated for incontinence severity (24h pad test), pelvic floor muscles strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes, and the number of pads), symptom severity (OAB-V8), quality of life (IIQ-7), treatment success (positive response rate), cure/improvement rate and treatment satisfaction (Likert scale). Result(s): There was no statistically significant differences in all parameters between the two groups at the end of the treatment. It was found that the treatment satisfaction scores, cure/improvement and positive response rates were not significantly different between two groups (p>0.05). Conclusion(s): We concluded that the application of IVES twice a week or 5 times a week added to BT were both effective on incontinence-related QoL and clinical parameters in women with refractory idiopathic OAB. These two IVES frequencies had similar clinical efficacy and patient satisfaction with a slight difference between them; 5 times per week IVES has a shorter treatment durationCopyright © 2022, International Braz J Urol.All Rights Reserved.

Yildiz, N. and R. Sonmez (2023). "Transcutaneous medial plantar nerve stimulation in women with idiopathic overactive bladder." Investigative and Clinical Urology 64(4): 395-403.
	Purpose: To define transcutaneous medial plantar nerve stimulation (T-MPNS) as a new neuromodulation method and assess the efficacy of T-MPNS on quality of life (QoL) and clinical parameters associated with incontinence in women with idiopathic overactive bladder (OAB). Material(s) and Method(s): Twenty-one women were included in this study. All women received T-MPNS. Two self-adhesive surface electrodes were positioned with the negative electrode near the metatarsal-phalangeal joint of the great toe on the medial aspect of the foot and the positive electrode 2 cm inferior-posterior of the medial malleolus (in front of the medio-malleolar-calcaneal axis). T-MPNS was performed 2 days a week, 30 minutes a day, for a total of 12 sessions for 6 weeks. Women were evaluated for incontinence severity (24-h pad test), 3-day voiding diary, symptom severity (Overactive Bladder Questionnaire [OAB-V8]), QoL (Quality of Life-Incontinence Impact Questionnaire [IIQ-7]), positive response and cure-improvement rates, and treatment satisfaction at baseline and at the 6th week. Result(s): Statistically significant improvement was found in the severity of incontinence, frequency of voiding, incontinence episodes, nocturia, number of pads, symptom severity, and QoL parameters at the 6th week compared with baseline. Treatment satisfaction, treatment success, and cure or improvement rates were found to be high at the 6th week. Conclusion(s): T-MPNS was first described in the literature as a new neuromodulation method. We conclude that T-MPNS is effective on both clinical parameters and QoL associated with incontinence in women with idiopathic OAB. Randomized controlled multicenter studies are needed to validate the effectiveness of T-MPNS.Copyright © The Korean Urological Association.

Yildiz, S., et al. (2023). "Role and effectiveness of progestins in pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and a meta-analysis." Minerva Obstetrics and Gynecology 75(6): 573-582.
	Introduction: Despite the many unknowns about its exact mechanism, progesterone and progestins are being successfully used to prevent luteinizing hormone (LH) surge during ovarian stimulation for assisted reproductive technology (ART). We will review progestin primed ovarian stimulation (PPOS) protocols in comparison with gonadotropin releasing hormone (GnRH) analogues and each other.; Evidence Acquisition: MEDLINE via PubMed; Cochrane Central Register of Controlled Trials (CENTRAL); Scopus; Web of Science were screened with keywords related to assisted reproductive technology, ovarian stimulation progesterone, GnRH analogue and progesterone in several combinations. Search period was from the date of inception of each database until 20 May 2022.; Evidence Synthesis: Live birth or ongoing pregnancy rate per embryo transfer (ET) was similar in PPOS and GnRH antagonist cycles (RR=1.16, 95% CI: 0.93-1.44). Clinical pregnancy rate per ET was likewise similar (RR=1.12, 95% CI: 0.92-1.37). Miscarriage rate per pregnancy was similar with PPOS and GnRH antagonists in autologous cycles (RR=1.01, 95% CI: 0.65-1.55). Pooled analyses showed similar live birth rate between progestins and short GnRH agonist protocols (RR=1.01, 95% CI: 0.49-2.09), however, clinical pregnancy rates per ET were significantly higher with progestins (RR=1.31, 95% CI: 1.06-1.62). Miscarriage rate per pregnancy was similar with progestins (RR=0.82, 95% CI: 0.55-1.21).; Conclusions: Progestins seem to be an efficient option for pituitary suppression during ovarian suppression, providing similar outcomes for stimulation and pregnancy. They can be especially beneficial for women for whom fresh ET is not considered.

Yılmaz, E. (2021). "The Determination of the Efficacy of Neural Therapy in Conservative Treatment-resistant Patients with Chronic Low Back Pain." Spine 46(14): E752‐E759.
	STUDY DESIGN: A randomized clinical trial. OBJECTIVE: The aim of this article is to determine the effectiveness of neural therapy (NT) in patients with chronic low back pain (LBP) who are resistant to medical and physical therapies. SUMMARY OF BACKGROUND DATA: Patients with LBP generally respond well to the treatment, whereas some cases do not improve via medical and physical therapies. Although trigger point injections (TPIs) may be an effective short‐term treatment in selected patients with LBP, they are not recommended in patients with chronic LBP due to a long‐lasting benefit not being demonstrated. METHODS: Fifty patients, who had inadequate functional recovery and pain relief, with chronic LBP were randomly divided into two groups: Group 1, only single TPI; Group 2, NT. NT including local‐segmental treatment (intradermal injections) on the lumbosacral region, 5 M injection (intradermal injections of the projection of the pelvic organs on the suprapubic region), pelvic plexus injection, i.v. injection (2 mL) for five sessions per a week. All patients in group 2 received the same kind of intervention every seance but interference field injections (injections into umbilicus for all patients and injections into scars resulting from vaccination and surgical operations such as cesarean section, if any) were also applied at the only first seance. The Visual Analog Scale (VAS) scores for current pain during activities and Roland Morris Disability Questionnaire (RMDQ) scores for disability were recorded at baseline and 1, 3, 6 months post‐injection. RESULTS: The VAS and RMDQ scores at 3 and 6 months were significantly lower in Group 2 versus Group 1 (P < 0.05). CONCLUSION: NT may be an alternative treatment option in patients with chronic LBP for pain relief and functional recovery in the long run.Level of Evidence: 2.

Yilmaz, G., et al. (2022). "Comparison of enhanced recovery protocol with conventional care in patients undergoing urogynecological surgery." Ceska gynekologie 87(4): 232-238.
	Objective: The impact of enhanced recovery after surgery (ERAS) protocol on postoperative outcomes after urogynecological surgery is yet to be a matter of investigation. This study sought to evaluate this issue by comparing the patients who had conventional or ERAS--guided perioperative care for several clinical end-points including ambulation, length of hospital stay (LOS), readmissions, and postoperative complications.; Materials and Methods: A total of 121 patients undergoing pelvic organ prolapse surgery were allocated to two study arms, ERAS protocol (Group E) or conventional care (Group C). Variables reflecting the restoration of appetite and bowel movements, bleeding events, other complications, LOS and readmissions were compared between the groups.; Results: The patients in Group C significantly received a more intensive intravenous fluid treatment compared to Group E (2,760 ± 656 vs. 1,045 ± 218 mL, P < 0.001). Time required for first flatus, first defecation, eating solid food, and ambulation (P < 0.001) were also longer in the former group of patients. Moreover, LOS was significantly reduced when the ERAS protocol was applied (2.5 ± 1.1 vs. 2.0 ± 0.6 days, P < 0.001). On the other hand, the two groups were similar with respect to the frequency of the postoperative complications, including surgical site infections, cardiovascular complications, non-specific abdominal pain, sub-ileus, blood loss and readmission rate.; Conclusion: In our sample population, ERAS protocol led to early initiation of oral intake, early recovery of bowel function, early mobilization, and early discharge of patients without compromise in safety concerns after urogynecological surgery.

Yılmaz, H. M., et al. (2023). "Comparison of the effectiveness of connective tissue massage and myofascial release technique in young adult women with primary dysmenorrhea." Journal of surgery & medicine (JOSAM) 7(1): 48‐53.
	Background/Aim: Dysmenorrhea can restrict daily living activities and the overall productivity of women, thereby negatively affecting quality of life and causing absenteeism in students and loss of workdays in working women. Medical treatment is frequently used in clinics, but alternative approaches are needed when currently available treatment options are not effective. The aim of this study is to investigate and compare the acute effects of two manipulative methods, connective tissue massage (CTM) and myofascial release technique (MRT), on menstrual pain, fatigue, pain threshold, and menstrual symptoms in young adult women with primary dysmenorrhea (PD). Methods: Forty young adults diagnosed with PD and scoring ≥4 in menstrual pain intensity according to the Visual Analog Scale (VAS) were included in the study. Menstrual pain and fatigue severity was evaluated by using VAS, pain threshold by algometer device from six unique points, and menstrual symptom severity using the Menstrual Symptom Questionnaire. Participants were randomly divided into two groups and evaluated in their first menstrual cycles. In Group 1, 10 sessions of CTM were applied between the first and second menstrual cycles, and in Group 2, a single session of MRT was applied on the most painful day of the second menstrual cycle. After the application, all participants were re-evaluated on the most painful day of their second menstrual cycles. Results: No statistically significant difference was found between the groups in terms of age, BMI, menarche age, menstrual cycle, and menstrual bleeding duration. In both groups, a significant decrease was found in pain, fatigue, and menstrual symptom severity, and a significant increase was found in pain threshold (P=0.001). MRT was found to be more effective at improving the pain threshold at all points except the first point (1st point P=0.098, 2nd point P=0.034, 3rd point P=0.037, 4th point P=0.041, 5th point P=0.009, 6th point P=0.001). Conclusion: It was found that CTM and MRT were effective at improving pain, fatigue, pain threshold, and menstrual symptoms in PD, and MRT was found to be more effective at increasing pain thresholds compared to CTM.

Yin, B., et al. (2022). "Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs." Frontiers in Microbiology 13: 899111.
	Chemotherapy is one of the most effective methods of systemic cancer treatment. Chemotherapy drugs are delivered through the blood circulation system, and they can act at all stages of the cell cycle, and can target DNA, topoisomerase, or tubulin to prevent the growth and proliferation of cancer cells. However, due to the lack of specific targets for chemotherapeutic agents, there are still unavoidable complications of cytotoxic effects. The effect of the microbiome on human health is clear. There is growing evidence of the potential relationship between the microbiome and the efficacy of cancer therapy. Gut microbiota can regulate the metabolism of drugs in several ways. The presence of bacteria in the tumor environment can also affect the response to cancer therapy by altering the chemical structure of chemotherapeutic agents and affecting their activity and local concentration. However, the underlying mechanisms by which the gut and tumor microbiota affect cancer therapeutic response are unclear. This review provides an overview of the effects of gut and tumor microbiota on the efficacy and adverse effects of chemotherapy in cancer patients, thus facilitating personalized treatment strategies for cancer patients.Copyright © 2022 Yin, Wang, Yuan, Li and Lu.

Yin, M., et al. (2019). "Identifying the superior surgical procedure for endometrial cancer: A protocol of network meta-analysis." Medicine 98(33): e16855.
	Background: Endometrial cancer (EC) is one of the most common gynecologic tumors, with a high incidence in developed countries. Although the overall prognosis is good, some women have invasive tumors, the risk of recurrence, and death is high. The common surgical methods used in EC are total-abdominal hysterectomy (TAH), total-vaginal hysterectomy (TVH), laparoscopic-assisted vaginal hysterectomy (LAVH), and total-laparoscopic hysterectomy (TLH) including both conventional and robotically assisted.; Methods: The literature search was performed in The Cochrane Central Register of Controlled Trials, PubMed, Web of Science, and Embase. The randomized controlled trials (RCTs) will be included. The search date is until June 2019. The risk of bias of included RCTs was assessed by 2 investigators according to the Cochrane Collaboration's tool. Network meta-analysis will be conducted by R software.; Results: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication.; Conclusion: This network meta-analysis will provide clinical staff with current and reliable information on the best surgical approach for EC. Ethical approval is not applicable, since this is a network mate-analysis based on published articles. The protocol has been registered on PROSPERO under the number CRD42019128094.

Yin, M., et al. (2022). "Impact of Adjuvant Chemotherapy on FIGO Stage I Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis." Frontiers in Oncology 12: 811638.
	Background: Ovarian clear cell carcinoma (OCCC) is an uncommon subtype of epithelial ovarian carcinoma (EOC) that is often diagnosed at an earlier stage in younger women. It remains uncertain whether adjuvant chemotherapy improves the prognosis of patients with stage I OCCC.; Objective: This systematic review and meta-analysis aimed to assess the impact of adjuvant chemotherapy on survival in patients with stage I OCCC.; Search Strategy: Eligible studies were screened from PubMed, Web of Science, Embase, and the Cochrane Library up to October 10, 2021.; Selection Criteria: Studies that compared the oncological outcomes of adjuvant chemotherapy with observation were included.; Data Collection and Analysis: Six studies comprising a total of 4553 patients were enrolled in our study, of whom 3320 (72.9%) patients had undergone adjuvant chemotherapy and 1233 (27.1%) had not.; Main Results: The 5-year disease-free survival (DFS) and 5-year overall survival (OS) of stage I OCCC were 82.7% and 86.3%, respectively. In the overall population, adjuvant chemotherapy did not improve the 5-year DFS (83.2% vs 83.7%, OR 0.77, 95% CI 0.21-2.82, P=0.69) or 5-year OS (87.3% vs 83.6%, OR 1.30, 95% CI 0.86-1.98, P=0.22). Further subgroup analysis on stage IA/IB suggested that adjuvant chemotherapy did not impact 5-year DFS (OR 0.20, 95% CI 0.01-5.29, P=0.34) or 5-year OS (OR 1.52, 95% CI 0.78-2.98, P=0.22). For stage IC including 1798 patients, adjuvant chemotherapy revealed a significant survival benefit for 5-year OS (84.5% vs 83.3%, OR 1.44, 95% CI 1.08-1.94, P=0.01). Furthermore, the administration of adjuvant chemotherapy was found to be associated with a better 5-year OS (OR 4.98, 95% CI 1.12-22.22, P=0.04) in stage IC2/3. But no inferences regarding the effect of AC on stage IC2/3 can be made due to the limited size of the non-AC arm.; Conclusion: This study indicated that adjuvant chemotherapy did not improve the prognosis of stage IA and IB OCCC patients. However, for patients with stage IC, due to the retrospective, heterogenous and older data with limited sample size, the pooled results of our study should be interpreted with caution. More prospective studies on the role of adjuvant chemotherapy in stage I OCCC are warranted.; Systematic Review Registration: PROSPERO, CRD42021287749.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yin, Yang, Zhou, Liu, Li and Zhang.)

Ying, M., et al. (2022). "The best choice of vaginal douching solution before oocyte retrieval among women with infertility: a systemic review and meta-analysis."
	
Ying, Z. and C. Sijing (2021). "Levonorgestrel-releasing intrauterine system versus medications for women with menorrhagia: A systematic review and meta-analysis."
	
Yingsha, Y. and J. Ruoan (2023). "Efficacy of sex hormone, not-hormone or surgery treatment in patients with endometrial hyperplasia with or without atypia: A network meta-analysis and systematic review of the literature."
	
Yingsha, Y. and X. Shuhang (2023). "Oncological and reproductive outcomes in women of endometrial hyperplasia with or without atypical: a meta-analysis."
	
yingyu, z., et al. (2024). "Comparison of the effect of plant extracts and non-steroidal anti-inflammatory drugs on relieving menstrual pain in women with primary dysmenorrhea."
	
Yiyue, F., et al. (2021). "Effects of adenomyosis on pregnancy outcomes in IVF/ICSI: systematic review and meta analysis."
	Review question To systematically review and summarize the existing evidence related to the effect of adenomyosis on fertility and on in vitro fertilization (IVF) clinical outcomes, and to explore the effects of medical treatments. Searches Electronic databases (PubMed, Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science and China National Knowledge Infrastructure (CNKI)) were searched from their inception until January 2021. Key search terms were the following text words: The following medical subject heading terms, keywords, and their combinations were used: “adenomyosis,’’‘‘adenomyoma,’’ ‘‘in vitro fertilization,’’ intracytoplasmic sperm injection,” ‘‘assisted reproductive technology,’’ ‘‘implantation rate,’’ ‘‘pregnancy,’’ ‘‘miscarriage,’’ ‘‘live birth,’’ ‘‘infertility,’’ ‘‘subfertility,’’ ‘‘treatment,” Types of study to be included RCT Condition or domain being studied Adenomyosis is a benign disorder where basal endometrial glands and stroma are found in the myometrium with reactive hyperplasia of the surrounding smooth muscle myometrial cells . Adenomyosis is associated with enlarged uterus, pelvic pain, excessive vaginal bleeding, and decreased quality of life . However, its effect on fertility remains debatable. Several theories have been proposed, including impaired uterotubal transport , reduced sperm function due to high levels of nitric oxide in the uterine cavity , impaired implantation, altered uterine contractility, and many others .A previous meta-analysis concluded that adenomyosis might have a negative impact on IVF treatment outcomes. It decreases the rates of implantation and clinical pregnancy and increases the miscarriage rate. The heterogeneity among the studies in that meta-analysis was high Participants/population Inclusion Criteria · Language: No language limited. Study designs: RCT. Population: Infertile women undergoing one or more IVF cycles. We also evaluated separately all articles comparingfertility outcomes in two groups of infertile adenomyosis patients untreated and treated surgically or medically. Intervention(s), exposure(s) 1.Infertile women with adenomyosis undergoing IVF. 2.Women with adenomyosis treated surgically or medically Comparator(s)/control 1.Infertile women without adenomyosis. 2.Infertile women with adenomyosis without surgically or medically Main outcome(s) clinical pregnancy rate after IVF Measures of effect RR Additional outcome(s) rates of implantation, ongoing pregnancy, live birth, miscarriage, and ectopic pregnancy. Measures of effect RR Data extraction (selection and coding) Titles and abstracts were independently screened by two authors (Y.F, S.Z). The same authors independently assessed studies for inclusion and extracted data about study features (design, country, and time of the study), populations (participants’ number and characteristics), type of intervention, IVF outcomes. A manual search of references of included studies was also performed in order to avoid missing relevant data. The results were compared, and any disagreement was resolved by consensus of the third reviewer (X.L). Risk of bias (quality) assessment The quality of the studies was evaluated using the Newcastle-Ottawa scale for observational and non-randomized studies Strategy for data synthesis Data analysis was performed by two Authors (Y.F, S.Z) using Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford, London). A. Dichotomous variables were analyzed using the risk ratio (RR) with a 95 % confidence interval (95 % CI). Significance level was set at P <0.05. Heterogeneity was measured using I² (Higgins I²). Analysis of subgroups or subsets Subgroup analysis considered patients with adenomyosis treated surgically or medically compared to women with adenomyosis without treatment Contact details for further information Xin Liang 184516824@qq.com Organisational affiliation of the review Chengdu University of Traditional Chinese Medicine Review team members and their organisational affiliations Yiyue Fan. School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine Shaomi Zhu. School of Medical and Life Sciences/Reproductive &Women-Children Hospital, Chengdu University of Traditional Chinese Medicine Xin Tan. School of Medical and Life Sciences/Reproductive &Women-Children Hospital, Chengdu University of Traditional Chinese Medicine Xin Liang. School of Medical and Life Sciences/Reproductive &Women-Children Hospital, Chengdu University of Traditional Chinese Medicine Type and method of review Systematic review Anticipated or actual start date 15 January 2021 Anticipated completion date 15 March 2021 Funding sources/sponsors This work is supported by National Science Fund for Distinguished Young Scholars (82004176) Conflicts of interest None known Language (there is not an English language summary)

Yizhou, H., et al. (2021). "Efficacy of antihyperglycemic drugs and inositol on polycystic ovary syndrome: A network meta-analysis." Chinese Journal of Endocrinology and Metabolism 37(12): 1096-1105.
	Objective The study was designed to evaluate the efficacy in polycystic ovary syndrome (PCOS) of glucagon-like peptide-1 receptor agonists (GLP-1RA), metformin combined with thiazolidinediones, alpha-glucosidase inhibitor, and inositol. Methods Eligible studies were searched in databases of PubMed, EMBase, Cochrane Library, Wanfang data, and CNKI based on population, interventions, comparisons, outcomes, and study design (PICOS) principle (inception to Nov 2020). Two researchers independently screened randomized controlled trials in strict accordance with the inclusion and exclusion criteria, extracted basic information and outcomes of included studies, and used Cochrane risk of bias tool to evaluate the methodological quality of the literature. Network meta-analysis was conducted by STATA 14. 0. Continuous variables without dimensional differences were calculated by weighted mean difference and 95% CI, and continuous variables with dimensional differences were calculated using standardized mean difference and 95% CI. Results A total of 27 studies with 1 445 patients were included in this study. Network meta-analysis showed that acarbose presented a better efficacy than other interventions in reducing total testosterone [surface under the cumulative ranking curve (SUCRA): 89.4%]. GLP-1RAs may have the best efficacy in reducing body mass index and homeostasis model assessment for insulin resistance (HOMA-IR; SUCRA: 99.1%, 89.2%, respectively), while using inositol may be a good choice to reduce serum fasting insulin, HOMA-IR, blood total cholesterol, and blood triglycerides (SUCRA: 94.5%, 85.4%, 96.6%, and 82.8%, respectively). Conclusions Acarbose may have advantages over other antihyperglycemic drugs in lowering blood testosterone. GLP-1RAs are more helpful to improve body mass index and HOMA-IR in PCOS patients. Inositol, as an insulin sensitizer, has a favorable effect on reducing fasting insulin, HOMA-IR, blood total cholesterol, and blood triglycerides, and there are no reports of side effects in current researches. Further study is still needed to confirm its efficacy.Copyright © Chinese Journal of Endocrinology and Metabolism.

yong, l., et al. (2022). "Pregnancy outcomes in tubal pregnancy with or without tubal preservation: a Meta-analysis."
	Review question to compare whether there is a difference about intrauterine pregnancy , repeat ectopic pregnancy rates between salpingostomy , methotrexate and salpingectomy, And whether there is a difference about pregnancy rate between no tuturing and tuturing tubal incision for salpingectomy. Searches We searched for PubMed, EMBASE, and Cochrane Library. From the establishment to In June 2022.in addition, all electronic databases are searched using the keywords "ectopic pregnancy" and "tubal pregnancy". Types of study to be included We included only randomized controlled trials (RCT). The primary outcome measures are the intrauterine pregnancy rate (including abortion), the ectopic pregnancy rate, and the tubal patency. Both reviewers independently judged all citations identified by the search strategy (Lin Yong and Long Yan). Abstracts of all citations are obtained to determine the eligible study. Complete reports of all eligible studies are obtained to assess whether these studies met pre-defined inclusion criteria. Condition or domain being studied Ectopic pregnancy refers to implantation of thegestational sac outside the uterine cavity, and the incidence of ectopic pregnancy in women in early pregnancy is 2%-3% [2]. Tubal pregnancy accounts for more than 90% of ectopic pregnancies, and is the first disease of maternal mortality in early pregnancy . Participants/population We included only randomized controlled trials (RCT). The primary outcome measures are the intrauterine pregnancy rate (including abortion), the ectopic pregnancy rate, and the tubal patency. Both reviewers independently judged all citations identified by the search strategy (Lin Yong and Long Yan). Abstracts of all citations are obtained to determine the eligible study. Complete reports of all eligible studies are obtained to assess whether these studies met pre-defined inclusion criteria. Intervention(s), exposure(s) We included only randomized controlled trials (RCT). The primary outcome measures are the intrauterine pregnancy rate (including abortion), the ectopic pregnancy rate, and the tubal patency. Both reviewers independently judged all citations identified by the search strategy (Lin Yong and Long Yan). Abstracts of all citations are obtained to determine the eligible study. Complete reports of all eligible studies are obtained to assess whether these studies met pre-defined inclusion criteria. Comparator(s)/control We included only randomized controlled trials (RCT). The primary outcome measures are the intrauterine pregnancy rate (including abortion), the ectopic pregnancy rate, and the tubal patency. Both reviewers independently judged all citations identified by the search strategy (Lin Yong and Long Yan). Abstracts of all citations are obtained to determine the eligible study. Complete reports of all eligible studies are obtained to assess whether these studies met pre-defined inclusion criteria. Main outcome(s) to compare the difference about intrauterine pregnancy and repeat ectopic pregnancy rates between salpingostomy and methotrexate , as well as the comparison with resection of fallopian tube operation method have or no differences, And whether there is a difference about pregnancy rate between no tuturing and tuturing tubal incision for salpingectomy. Additional outcome(s) no Data extraction (selection and coding) We included only randomized controlled trials (RCT). The primary outcome measures are the intrauterine pregnancy rate (including abortion), the ectopic pregnancy rate, and the tubal patency. Both reviewers independently judged all citations identified by the search strategy (Lin Yong and Long Yan). Abstracts of all citations are obtained to determine the eligible study. Complete reports of all eligible studies are obtained to assess whether these studies met pre-defined inclusion criteria. Disagreements of opinion are registered and resolved by consensus with all authors. For eligible studies, we collect relevant information, ectopic pregnancy characteristics ( ectopic pregnancy size, mean serum hCG concentration), interventions, and outcomes. Whenever required, we seek to retrieve the missing data by contacting the primary authors. Risk of bias (quality) assessment For RCT, we performed a risk bias assessment according to the criteria in the Systematic Evaluation Manual of Cochrane Interventions. Strategy for data synthesis Statistical analysis is performed using the Review Manager 5.3 software, The odds ratio (OR) and 95% credible interval (CI) are used as effect indicators for count data analysis; heterogeneity test: Cochrane Q test (square) and I² (test level set as =0.05), When I² ≥50% or P <0.1, that indicates the study has great heterogeneity, subgroup analysis is conducted to explore the factors leading to non-homogeneity from the perspectives of clinical and methodological heterogeneity. After excluding the influence of obvious clinical heterogeneity, a random effect model is used for analysis; descriptive analysis is used if there is too much heterogeneity or clinical heterogeneity between the two groups. When I² <50%, and P≥ 0.1, the inter-study heterogeneity is considered small, and the fixed-effect models are selected for merging. Taking the study effect size as the horizontal axis and the standard effect size mistakenly as the vertical axis, the funnel scatters plot is drawn to determine whether there is publication bias. Analysis of subgroups or subsets no Contact details for further information yong lin 2043359232@qq.com Organisational affiliation of the review Luzhou Maternal and child Health Care Hospital Review team members and their organisational affiliations Dr yong lin. Luzhou Maternal and child Health Care Hospital Mrs yan long. Luzhou Maternal and child Health Care Hospital Mrs rong zhu. Luzhou Maternal and child Health Care Hospital Mrs jin he. Luzhou Maternal and child Health Care Hospital Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 30 June 2022 Anticipated completion date 11 October 2022 Funding sources/sponsors Luzhou Maternal and child Health Care Hospital Conflicts of interest None known Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Female; Humans; Methotrexate; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Pregnancy, Tubal; Salpingectomy; Salpingostomy Date of registration in PROSPERO 22 September 2022 Date of first submission 11 September 2022 Details of any existing review of the same topic by the same authors not

Yonkers, K. A., et al. (2023). "Management of Premenstrual Disorders." Obstetrics and Gynecology 142(6): 1516-1533.
	PURPOSE: To provide recommendations for the management of premenstrual syndrome and premenstrual dysphoric disorder, collectively referred to as premenstrual disorders, based on assessment of the evidence regarding the safety and efficacy of available treatment options. An overview of the epidemiology, pathophysiology, and diagnosis of premenstrual disorders also is included to provide readers with relevant background information and context for the clinical recommendations. TARGET POPULATION: Reproductive-aged adults and adolescents with premenstrual symptoms. METHOD(S): This guideline was developed using an a priori protocol in conjunction with a writing team consisting of two specialists in obstetrics and gynecology appointed by the ACOG Committee on Clinical Practice Guidelines- Gynecology and one external subject matter expert. ACOG medical librarians completed a comprehensive literature search for primary literature within Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development and Evaluations) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements. RECOMMENDATIONS: This Clinical Practice Guideline includes recommendations on the following evidence-based treatment options for premenstrual disorders, with an acknowledgement that many patients may benefit from a multimodal approach that combines several interventions: pharmacologic agents (hormonal and nonhormonal), psychological counseling, complementary and alternative treatments, exercise and nutritional therapies, patient education and self-help strategies, and surgical management. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence. Based on review of extrapolated data from adult populations and expert consensus, it was determined that the recommendations also apply to adolescents, with a few exceptions that are noted in the Clinical Practice Guideline.Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc.

Yonkers Kimberly, A., et al. (2023). "Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial." Journal of clinical psychopharmacology 43(4): 320-325.
	Purpose/background: Daily treatment with sertraline improves functional impairment among individuals with premenstrual dysphoric disorder (PMDD). We do not know whether treatment initiated at symptom onset also improves functional impairment.; Methods/procedures: This 3-site, double blind, randomized, clinical trial compared sertraline (25-100 mg) to similar appearing placebo, both administered at symptom onset, for reduction of PMDD symptoms. Ninety participants were allocated to sertraline and 94 participants to placebo. Functional outcomes from the Daily Ratings of the Severity of Problems included (1) reduced productivity or efficiency at work, school, home, or daily routine; (2) interference with hobbies or social activities; and (3) interference with relationships. Items were measured from 1 (no interference) to 6 (extreme interference) and averaged for the final 5 luteal phase days. This secondary analysis examined whether improvement in functional domains was greater for those allocated to sertraline compared with placebo. Second, we used causal mediation analyses to explore whether specific PMDD symptoms mediated functional improvement.; Results/findings: Only relationship functioning improved significantly with active treatment between baseline and the end of the second cycle (active group mean [SD] change, -1.39 [1.38]; placebo group mean change, -0.76 [1.20]; β = -0.40; SE, 0.15; P = 0.009). The total effect of treatment on interference was -0.37 (95% confidence interval [CI], -0.66 to -0.09; P = 0.011). Given the nonsignificant direct effect (0.11; 95% CI, -0.07 to 0.29; P = 0.24) and significant indirect effect (-0.48; 95% CI, -0.71 to -0.24; P < 0.001), amelioration of anger/irritability likely mediated reductions in relationship interference.; Implications/conclusions: That anger/irritability mediates impairments in relationship functioning has face validity but should be replicated in other data sets.; Trial Registration: ClinicalTrials.gov identifier NCT00536198 . (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Yono, M., et al. (2021). "TAS-303 effects on urethral sphincter function in women with stress urinary incontinence: phase I study." International Urogynecology Journal 32(3): 673‐680.
	Introduction and hypothesis: TAS‐303, which selectively inhibits noradrenaline reuptake, was developed for treating stress urinary incontinence (SUI). The proximal urethra mainly comprises smooth muscle fibers in which α1 adrenergic receptors are abundant. This study was conducted to evaluate the effect of TAS‐303 on urethral function and its safety profile in female patients with SUI. Methods: In total, 16 women (age, 20–64 years) with SUI and > 5.0 g of leakage in the 1‐h pad test at screening were randomized and administered the assigned treatment in a double‐blind manner. The primary end point was change in the maximal urethral closure pressure (MUCP) at 6 h post‐dose. The secondary end point was change in the urethral closure pressure of the entire urethra and each urethral region (proximal, middle, and distal) at 6 h post‐dose. The results were analyzed using a t‐test. Results: The mean change ± standard deviation in MUCP at 6 h post‐dose was 3.473 ± 12.154 cmH2O for TAS‐303 and 2.615 ± 9.794 cmH2O for placebo (between‐group difference: 0.858 cmH2O, P = 0.8047). The mean changes ± standard deviation in urethral closure pressure of the proximal urethra at 6 h after the administration of TAS‐303 18 mg and placebo were 3.863 ± 10.941 and 1.634 ± 12.093, respectively (between‐group difference: 2.229 cmH2O, P = 0.5976). Conclusions: No significant difference in MUCP and urethral closure pressure was found between TAS‐303 and placebo. However, the change in the proximal urethral closure pressure with TAS‐303 was larger than that with placebo. This suggests that TAS‐303 has pharmacological effects on urethral sphincteric function.

Yoon, B. K. (2023). "The impacts of menopausal hormone therapy on longer-term health consequences of ovarian hormone deficiency." Climacteric : the journal of the International Menopause Society 26(3): 193-197.
	This study on the longer-term health consequences of ovarian hormone deficiency (OHD) received the Henry Burger Prize in 2022. Osteoporosis, cardiovascular disease and dementia are major degenerative diseases that are also causally associated with OHD. Two randomized controlled trials (RCTs) revealed no significant difference in bone mineral density by adding alendronate to ongoing menopausal hormone therapy (MHT) or combining alendronate at MHT initiation. Another RCT pursuing the effects on fracture recurrence and total mortality in women with hip fracture disclosed that MHT with percutaneous estradiol gel (PEG) and micronized progesterone (MP4) was comparable to risedronate. Basic studies reported that 17β-estradiol exerted direct beneficial actions on vascular smooth muscle in cell proliferation, fibrinolysis and apoptosis. A fourth RCT showed that MP4 had a neutral impact on the PEG response of blood pressure and arterial stiffness. A fifth RCT suggested that the combination therapy of conjugated equine estrogen and MP4 was superior to tacrine in preserving activities in daily living in women with Alzheimer's disease. In addition, PEG plus MP4 attenuated cognitive decline in women with mild cognitive impairment in a sixth RCT. Finally, the all-cause mortality in recently menopausal women receiving MHT was updated using an adaptive meta-analysis of four RCTs.

Yoshida, K., et al. (2021). "Laparoscopic Versus Robotic Hysterectomy in Obese Patients With Early-stage Endometrial Cancer: A Single-centre Analysis." Anticancer Research 41(8): 4163-4167.
	BACKGROUND/AIM: To compare the surgical outcomes of robotic and laparoscopic hysterectomy with or without pelvic lymphadenectomy among obese patients [body mass index (BMI) >30 kg/m2] with early-stage endometrial cancer. PATIENTS AND METHODS: We examined 42 obese patients with early-stage endometrial cancer who underwent laparoscopic (LH) or robotic hysterectomy (RH) between April 2014 and April 2020 in our institution. We analysed intraoperative and postoperative data for both procedures. RESULTS: Of the 42 women, 22 and 20 patients underwent RH and LH, respectively, with or without pelvic lymphadenectomy. The operation times, harvested lymph nodes, and BMI did not differ between the groups. In the subset of patients who underwent pelvic lymphadenectomy, those in the RH group had shorter hospital stays (p=0.001) and less intraoperative bleeding (p=0.006). CONCLUSION: Obese patients with endometrial cancer who underwent robotic surgery had less blood loss and shorter hospital stays than those who underwent laparoscopic surgery.

Yoshida, M., et al. (2022). "Efficacy of TAC-302 for patients with detrusor underactivity and overactive bladder: a randomized, double-blind, placebo-controlled phase 2 study." World Journal of Urology 40(11): 2799‐2805.
	PURPOSE: This multicenter, randomized, double‐blind, placebo‐controlled phase 2 study evaluated the efficacy and safety of TAC‐302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB). METHODS: After 2‐4 weeks of observation, patients were randomized 2:1 to receive oral TAC‐302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety. RESULTS: Seventy‐six patients were included (TAC‐302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p < 0.001) with TAC‐302 (n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p < 0.001) with TAC‐302 (n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC‐302 significantly increased BCI in males and BVE in both sexes. TAC‐302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred. CONCLUSION: Considering the significant effects on BCI in males and BVE in both sexes, TAC‐302 may benefit patients with DU. REGISTRATION: ClinicalTrials.gov Identifier NCT03175029 registered 6/5/2017.

Yoshida, M., et al. (2021). "Cardiovascular safety of vibegron, a new β3-adrenoceptor agonist, in older patients with overactive bladder: post-hoc analysis of a randomized, placebo-controlled, double-blind comparative phase 3 study." Neurourology and Urodynamics 40(6): 1651‐1660.
	Aims: To examine the safety and efficacy of vibegron, a new β3‐adrenoceptor agonist, in patients aged ≥65 years, with a focus on the effects on cardiovascular system and overactive bladder (OAB) symptoms. Methods: A post‐hoc subgroup analysis was performed of a randomized, placebo‐controlled, double‐blind comparative phase 3 study of vibegron, including those assigned to receive either vibegron 50 mg (V50), vibegron 100 mg (V100), or placebo for 12 weeks. Subjects were stratified into two subgroups based on age: a <65‐year subgroup and a ≥65‐year subgroup. Safety (changes in systolic and diastolic blood pressure, pulse rate, and residual urine volume) and efficacy (changes in the numbers of micturitions, urgency episodes, urgency urinary incontinence [UUI] episodes, and the voided volume/micturition) were assessed in the subgroups treated with vibegron vs. placebo. Results: There were no significant differences in the cardiovascular outcomes (blood pressure and pulse rate), nor in the changes in residual urine volume, between the V50/100 and placebo groups in the <65‐year or ≥65‐year subgroup after 12‐week treatment. Adverse events were slightly increased in the ≥65‐year subgroup. In the efficacy analysis, V50/100 demonstrated similar efficacy in the <65‐year and ≥65‐year subgroups; an increasing trend in the voided volume/micturition was observed in subjects aged ≥65 years compared to subjects aged <65 years. Conclusions: Vibegron was suggested to be similarly effective in patients ≥65 and <65 years and to have minimal influence on cardiovascular parameters.

Yoshikata, R., et al. (2021). "Effects of an equol-containing supplement on advanced glycation end products, visceral fat and climacteric symptoms in postmenopausal women: a randomized controlled trial." PloS One 16(9): e0257332.
	Introduction Equol, an isoflavone derivative whose chemical structure is similar to estrogen, is considered a potentially effective agent for relieving climacteric symptoms, for the prevention of lifestyle‐related diseases, and for aging care in postmenopausal women. We investigated the effect of an equol‐containing supplement on metabolism and aging and climacteric symptoms with respect to internally produced equol in postmenopausal women. Methods A single‐center, randomized controlled trial (registration number: UMIN000030975) on 57 postmenopausal Japanese women (mean age: 56�5.37 years) was conducted. Twenty‐seven women received the equol supplement, while the remaining received control. Metabolic and aging‐related biomarkers were compared before and after the 3‐month intervention. Climacteric symptoms were assessed every month using a validated self‐administered questionnaire in Japanese postmenopausal women. Results Three months post‐intervention, the treatment group showed significant improvement in climacteric symptoms compared to the control group (81% vs. 53%, respectively, p = 0.045). We did not observe any beneficial effect on metabolic and aging‐related biomarkers in the intervention group. However, in certain populations, significant improvement in skin autofluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. Conclusion Women receiving equol supplementation showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously produced equol to improve skin aging and visceral fat in certain populations.

Yoshino, O., et al. (2022). "Quality of Life in Japanese Patients with Dysmenorrhea or Endometriosis-Associated Pelvic Pain Treated with Extended Regimen Ethinylestradiol/Drospirenone in a Real-World Setting: A Prospective Observational Study." Advances in Therapy 39(11): 5087-5104.
	Introduction: Dysmenorrhea and endometriosis are common gynecologic disorders among women of reproductive age that significantly impact health-related quality of life (HRQL) as well as productivity. Although there are treatment options listed in Japanese guidelines, a gap remains in unmet medical needs for maximizing treatment outcome. The extended regimen of ethinylestradiol and drospirenone (EE/DRSP) (taken daily for up to 120 consecutive days) has been available in Japan for treating dysmenorrhea and/or endometriosis-associated pain since 2016. Yet, the effectiveness of its usage on HRQL has not been investigated elsewhere to date. Therefore, in this study, we aim to observe changes in HRQL of Japanese women treated with an extended regimen of EE/DRSP for dysmenorrhea and/or endometriosis-associated pain.; Methods: As part of a 2-year post-marketing surveillance study, women with dysmenorrhea or endometriosis-associated pelvic pain were prescribed extended EE/DRSP during routine clinical practice. Data were collected 1 month before and 3 and 6 months after initiating treatment. Primary outcomes were the Menstrual Distress Questionnaire (MDQ) (before, during, and after menstruation) in patients with dysmenorrhea, and the Endometriosis Impact Scale (EIS) and European Quality of Life 5-dimensions 5-level instrument (EQ-5D-5L) in patients with endometriosis.; Results: The study cohort included 315 patients (mean age 28.9 years) with dysmenorrhea and 262 patients (mean age 31.3 years) with endometriosis. Mean MDQ total scores before and during menstruation decreased significantly after 6 months with extended EE/DRSP; there was no improvement in after-menstruation MDQ score. Mean EIS domain scores improved significantly by 6 months, with improvement in most EIS individual item scores. Mean EQ-5D-5L scores increased slightly during 6 months of treatment.; Conclusions: Extended EE/DRSP treatment improved HRQL outcomes in Japanese women with dysmenorrhea or endometriosis-associated pelvic pain.; Trial Registration: Registered at ClinicalTrials.gov (NCT03126747) on June 2017. (© 2022. The Author(s).)

Yoshino, O., et al. (2022). "Menstrual Symptoms, Health-Related Quality of Life, and Work Productivity in Japanese Women with Dysmenorrhea Receiving Different Treatments: Prospective Observational Study." Advances in Therapy 39(6): 2562-2577.
	Introduction: Dysmenorrhea is a physical and mental burden for women, negatively affecting health-related quality of life (HRQL) and work productivity. However, data on HRQL and work productivity of Japanese women are scarce.; Methods: In this prospective observational study, 397 Japanese women received low-dose estrogen/progestin (LEP) or non-LEP treatment (non-steroidal anti-inflammatory drugs or Chinese herbal medicines) for primary/secondary dysmenorrhea and completed survey questionnaires online regarding menstrual symptoms, HRQL, and work productivity. Regression analysis was performed to compare the groups and evaluate outcomes over time using the paired t test. Subgroup analysis was performed using stratification by patient background, and correlations between improvement in menstrual symptoms/HRQL and work productivity were investigated using Spearman's rank correlation coefficient.; Results: Significant reductions in the modified Menstrual Distress Questionnaire (mMDQ) total score were shown in the LEP group (n = 251) (P < 0.01), but not the non-LEP group (n = 146). Significant improvements in HRQL, measured by the 36-Item Short-Form Health Survey v2.0 (SF-36v2.0), were shown in the LEP group, but not the non-LEP group. Improvements were seen in mental component summary and 7/8 domains (role physical, bodily pain, general health, role emotional, mental health, vitality, and social functioning) in the LEP group, but not the non-LEP group. There were no differences in the physical component summary and role functioning in either group. Improvements in work productivity, measured by the modified Work Productivity and Activity Impairment Questionnaire (mWPAI), were greater in the LEP group vs. non-LEP group. Regression analysis showed differences in improvements between the groups in the mMDQ total score, SF-36v2.0, and mWPAI. A correlation between mMDQ or HRQL and work productivity was seen.; Conclusion: In Japanese women, dysmenorrhea is associated with reduced HRQL and work productivity. In real-world clinical practice, improvements in physical and mental menstrual symptoms, HRQL, and work productivity were observed with LEP treatment.; Trial Registration: NCT04607382 (ClinicalTrials.gov). (© 2022. The Author(s).)

Yossi, S., et al. (2020). "[Radiotherapy for ovarian carcinoma management: Literature review]." Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique 24(2): 159-165.
	Ovarian cancer is the fifth most common cancer in women in France with 4714 new cases in 2017. More than 70% of patients whose disease is initially locally advanced will present locoregional or distant recurrence. Therapeutic options in this situation are not consensual. They are based on chemotherapy possibly associated with an iterative cytoreductive surgery when it is bearable by the patient. The place of radiotherapy in the management of the disease is hidden in the vast majority of national or international standards. We conducted a general review of the literature to clarify the role of irradiation in the global management of ovarian cancers, particularly in recurrence. (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Younis, J. S. (2022). "Endometriosis-Associated Ovarian Cancer: What Are the Implications for Women with Intact Endometrioma Planning for a Future Pregnancy? A Reproductive Clinical Outlook." Biomolecules 12(11): 1721.
	Endometriosis is a chronic, universal, and prevalent disease estimated to affect up to 1:10 women of reproductive age. Endometriosis-associated ovarian cancer (EAOC) developing at reproductive age is challenging and of concern for women and practitioners alike. This outlook review focuses on the occurrence of EAOC, especially in infertile women or those planning for a future pregnancy, from the perspective of a reproductive endocrinologist, based on recent evidence. Contemporary pathogenesis, genetic profiles, evidence of causality, clinical diagnosis, prognosis, and up-to-date management are discussed. EAOC seems to be merely associated with endometrioma and includes clear-cell and endometrioid ovarian carcinoma. Although endometrioma is frequently found in women of reproductive age (up to 1:18 of women), EAOC appears to be a rare occurrence. These women are of more advanced reproductive age, nulliparous, and hyperestrogenic, with a large-sized unilateral endometrioma (>9 cm) containing solid components and papillary projections. Each case suspected to have EAOC has specific characteristics, and a multidisciplinary discussion and appropriate patient counseling should be conducted to reach an optimal therapeutic plan. Since most of these cases are diagnosed at an early stage with a favorable prognosis, fertility-sparing surgery may be feasible. The pros and cons of fertility preservation techniques should be discussed.Copyright © 2022 by the author. Licensee MDPI, Basel, Switzerland.

Yousefi, M., et al. (2023). "Evaluation of Pregnancy Outcomes in Women with Recurrent Implantation Failure after Intrauterine Receiving Peripheral Blood Mononuclear Cells: A Clinical Trial." Iranian Journal of Medical Sciences 48(1 Supplement): 45.
	Background: Some recurrent implantation failure (RIF) patients have no anatomical and serological problems but more accurate immunological tests show low Th-17/Treg ratio. We intended to investigate the effect of intrauterine administration of autologous human chorionic gonadotropin (hCG)-activated peripheral blood mononuclear cells (PBMCs) in RIF women with low helper T(Th)17/ regulatory T (Treg) cell ratio. Method(s): 100 women with at least three in vitro fertilization / embryo transfer (ET) failure and low Th-17/Treg ratio compared to healthy control were selected from 248 women who volunteered for PBMC-therapy. These 100 women were randomly divided into PBMC receiving (n=50) and control (n=50) groups. After the PBMCs were taken from the patients, they were treated with hCG for 48 hours. Then two days before ET and in the study group, PBMCs were administered into the uterine cavity. The inflammatory cytokines' concentration was investigated in the supernatant of cultured PBMCs after 2, 24, and 48 hours incubation by the enzyme-linked immunosorbent assay method. Result(s): The Th-17, Treg frequency and the Th-17/Treg ratio was notably lower in RIF group than the healthy controls (P<0.0001). The inflammatory cytokines secretion was remarkably higher after 48 hours in comparison with 2 and 24 hours (P<0.0001). The pregnancy and live birth rate were considerably increased in PBMC-therapy group compared to phosphate buffer saline ( PBS) -injecting (control) group (P=0.032 and P=0.047, respectively). The miscarriage rate was significantly lower in women undergoing PBMC- therapy (P=0.029). Conclusion(s): According to our study, intrauterine injection of autologous hCG-activated PBMCs ameliorates pregnancy outcomes in patients with at least three IVF/ET failures.

Youssef, A., et al. (2022). "Development of the OPAL prediction model for prediction of live birth in couples with recurrent pregnancy loss: protocol for a prospective and retrospective cohort study in the Netherlands." BMJ Open 12(9): e062402.
	Introduction: Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before 24 weeks gestation. Despite extensive diagnostic workup, in only 25%-40% an underlying cause is identified. Several factors may increase the risk for miscarriage, but the chance of a successful pregnancy is still high. Prognostic counselling plays a significant role in supportive care. The main limitation in current prediction models is the lack of a sufficiently large cohort, adjustment for relevant risk factors, and separation between cumulative live birth rate and the success chance in the next conception. In this project, we aim to make an individualised prognosis for the future chance of pregnancy success, which could lead to improved well-being and the ability managing reproductive choices.; Methods and Analysis: In this multicentre study, we will include both a prospective and a retrospective cohort of at least 931 and 1000 couples with RPL, respectively. Couples who have visited one of the three participating university hospitals in the Netherlands for intake are eligible for the study participation, with a follow-up duration of 5 years. General medical and obstetric history and reports of pregnancies after the initial consultation will be collected. Multiple imputation will be performed to cope for missing data. A Cox proportional hazards model for time to pregnancy will be developed to estimate the cumulative chance of a live birth within 3 years after intake. To dynamically estimate the chance of an ongoing pregnancy, given the outcome of earlier pregnancies after intake, a logistic regression model will be developed.; Ethics and Dissemination: The Medical Ethical Research Committee of the Leiden University Medical Center approved this study protocol (N22.025). There are no risks or burden associated with this study. Participant written informed consent is required for both cohorts. Findings will be published in peer-reviewed journals and presentations at international conferences.; Trial Registration Number: NCT05167812.; Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Yu, H., et al. (2023). "Impact of hemostatic methods on ovarian reserve after laparoscopic ovarian cystectomy for benign and endometriotic ovarian tumor: A Systematic review and meta-analysis."
	Review question Impact of hemostatic methods on ovarian reserve after laparoscopic ovarian cystectomy for benign and endometriotic ovarian tumor P:patients with a diagnosis of endometrioma or other benign ovarian tumor who underwent laparoscopic surgery I: bipolar hemostatic method for ovary during laparoscopic surgery C:non-thermal hemostatic method O: ovarian reserve (AMH, AFC..) Searches PubMed/MEDLINE, Cochrane Library, Web of Science/Knowledge, Embase, before October 2022 Types of study to be included RCT Condition or domain being studied gynecology, ovarian reserve after laparoscopic surgery Participants/population Inclusion criteria: patients with a diagnosis of endometrioma or other benign ovarian tumor who underwent laparoscopic surgery Exclusion criteria: patients with suspect malignanc Intervention(s), exposure(s) bipolar electrohemostatic method during laparoscopic surgery Comparator(s)/control non-hemostatic method used during laparoscopic surgery Main outcome(s) ovarian reserve(post operative AMH, AFC) Additional outcome(s) Not applicable

Yu, K. and T. Zhang (2023). "A systematic review of the literature of randomized controlled studies of kidney tonic treatment for threatened miscarriage."
	Review question: This study is only used to evaluate and evaluate the efficacy of kidney-tonifying Chinese medicines on threatened miscarriage. Searches: Computer search English database package Including Cochrane Library, Embase, PubMed, Chinese database package Including CNKI, Wanfang Database, VIP, and China Biomedical Literature Contribute to the database. Types of study to be included This review was mainly a RCT study. Condition or domain being studied Threatened miscarriage is a major focus of modern infertility diseases, and compared with Western medicine, TCM treatment has fewer side effects and has unique advantages. Participants/population Inclusion criteria: (1) Randomised clinical trials (RCTs), whether or not single-blind, double-blind, or unblinded. (2) Research subjects: patients with threatened miscarriage combined with clinical examination. (3) Including control group and treatment group. Trials consisted of parallel control groups receiving other drugs (including Western medicines), placebo, or no treatment. (4) The intervention was the use of traditional Chinese medicine to tonify the kidney, or combined with other drugs (including Western medicine) for the treatment of threatened miscarriage. (5) The balance and baseline between case groups were consistent, and the comparability was good. (6) Outcome indicators: Efficacy of traditional Chinese medicine for kidney tonics. Exclusion criteria: (1) the data is incomplete and unusable; (2) non-use of traditional Chinese medicine for kidney tonics; (3) patients with non-threatened miscarriage; (3) non-control group experiments, non-randomized and other poor-quality clinical bed research literature, (4) animal experiments; (5) The balance and baseline between case groups were inconsistent, and the comparability was not good; (6) The baseline data of the selected literature were not similar;7. Those who were treated with external treatment by traditional Chinese medicine. Intervention(s), exposure(s) The intervention was the use of traditional Chinese medicine (TCM) for the treatment of threatened miscarriage with kidney tonic herbs or in combination with other drugs (including Western medicine rather than TCM external treatment). Comparator(s)/control: Trials included parallel control groups receiving other drugs (including Western medicines rather than TCM external treatments), placebo, or no treatment. Main outcome(s): ex hormones, AMH, TCM pattern scores, clinical symptoms, pregnancy rate, etc. Additional outcome(s): quality of life

yu, L. and C. Jiao (2021). "Effectiveness and safety of Acupuncture and moxibustion in the treatment of insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis."
	
Yu, L., et al. (2020). "Manual acupuncture versus sham acupuncture and usual care for the prevention of primary dysmenorrhea (PD): study protocol for a randomized controlled trial." Trials 21(1): 818.
	Background: Primary dysmenorrhea (PD) is a leading cause of dysmenorrhea among adolescent girls. Manual acupuncture may be considered as an effective treatment for PD, but high-quality evidence remains limited. This trial aims to evaluate the efficacy and safety of acupuncture for the prevention of PD as compared with sham acupuncture and usual care.; Methods/design: This is a three-arm, randomized, controlled clinical trial in which the patients, assessors, and statisticians will be blinded. A total of 300 acupuncture-naive patients who were diagnosed as PD will be randomly allocated to the verum acupuncture, sham acupuncture, or usual care groups in a 2:2:1 ratio. Patients in the verum acupuncture group will receive manual acupuncture at specific acupuncture points with penetrating needling, while those in the sham acupuncture group will receive non-penetrating needling at non-acupuncture points. They will be given five sessions over a menstrual cycle for 3 menstrual cycles. Patients in the usual care group will receive health education and informed to receive manual acupuncture for free after waiting for 7 menstrual cycles. The primary outcome will be the change from baseline in the Cox Menstrual Symptom Scale Score (CMSS). The secondary outcomes will be the changes in Massachusetts General Hospital Acupuncture Sensation Scale (MASS), visual analog scale (VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI- II), Acupuncture Expectancy Scale (AES), 60-item NEO Personality Inventory-Short Form (NEO-FFI), and acute medication intake. The adverse events will be recorded at every visit. The analyses will be performed base on a full analysis set (FAS) and a per-protocol set (PPS).; Discussion: This study may provide high-quality evidence regarding the efficacy and safety of manual acupuncture for PD. In addition, the results of this study will help to identify the efficacy of acupuncture due to the specific effects of acupuncture or placebo effects of acupuncture ritual.; Trial Registration: Clinical Trials.gov NCT02783534 . Registered on 26 May 2016.

Yu, L., et al. (2021). "The efficacy and safety of MR-HIFU and US-HIFU in treating uterine fibroids with the volume <300 cm 3 : a meta-analysis." International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 38(1): 1126-1132.
	Background: High-intensity focused ultrasound (HIFU) is a promising and non-invasive therapy for symptomatic uterine fibroids. Currently, the main image-guided methods for HIFU include magnetic resonance-guided (MR-HIFU) and ultrasound-guided (US-HIFU). However, there are few comparative studies on the therapeutic efficacy and safety of MR-HIFU and US-HIFU in treating symptomatic uterine fibroids with a volume <300 cm 3 .; Objective: We performed this meta-analysis to evaluate the efficacy and safety of MR-HIFU and US-HIFU in treating symptomatic uterine fibroids with a volume <300 cm 3 .; Methods: We searched relevant literature in PubMed, EMBASE, Cochrane Library CNKI from inception until 2021. The mean value, the proportion, and their 95% confidence intervals (CIs) were measured by random-effects models. Publication bias was assessed using funnel plots.; Results: 48 studies met our inclusion criteria-28 describing MR-HIFU and 20 describing US-HIFU. The mean non-perfused volume rate (NPVR) was 81.07% in the US-HIFU group and 58.92% in the MR-HIFU group, respectively. The mean volume reduction rates at month-3, month-6, and month-12 were 42.42, 58.72, and 65.55% in the US-HIFU group, while 34.79, 37.39, and 36.44% in the MR-HIFU group. The incidence of post-operative abdominal pain and abnormal vaginal discharge in the US-HIFU group was lower than that of MRI-HIFU. However, post-operative skin burn and sciatic nerve pain were more common in the US-HIFU group compared with MRI-HIFU. The one-year reintervention rate after MR-HIFU was 13.4%, which was higher than 5.2% in the US-HIFU group.; Conclusion: US-HIFU may show better efficiency and safety than MR-HIFU in treating symptomatic fibroids with a volume <300 cm 3 .

Yu, M., et al. (2023). "Effect of levothyroxine on the pregnancy outcomes in recurrent pregnancy loss women with subclinical hypothyroidism and thyroperoxidase antibody positivity: a systematic review and meta-analysis." The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 36(2): 2233039.
	Objective: This study aimed to explore the effects of levothyroxine on pregnancy outcomes and thyroid function in recurrent pregnancy loss (RPL) women with subclinical hypothyroidism (SCH) or thyroperoxidase antibody positivity (TPOAb + ).; Methods: Literature search was performed from inception to 24 June 2022. The heterogeneity for each outcome was evaluated using Cochran's Q test and quantified with I-squared ( I 2 ). Pooled effect sizes were expressed as relative risk (RR) and weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Stability of the results were assessed using the sensitivity analysis.; Results: Fifteen eligible studies with 1911 participants were included in this meta-analysis. The pooled data showed that levothyroxine decreased premature delivery rate (RR = 0.48, 95%CI: 0.32, 0.72), miscarriage rate (RR = 0.59, 95%CI: 0.44, 0.79), premature rupture of membranes (PROM) rate (RR = 0.44, 95%CI: 0.29, 0.66), and fetal growth restriction rate (RR = 0.33, 95%CI: 0.12, 0.89) in RPL women with TPOAb + . In RPL women with SCH, live birth rate was elevated (RR = 1.20, 95%CI: 1.01, 1.42) and miscarriage rate was reduced (RR = 0.65, 95%CI: 0.44, 0.97) by levothyroxine. In addition, levothyroxine substantially decreased TSH level (WMD = -0.23, 95% CI: -0.31, -0.16) and TPO level (WMD = -23.48, 95%CI: -27.50, -19.47).; Conclusions: Levothyroxine improved pregnancy outcomes and thyroid function in RPL women with TPOAb + or SCH, indicating that levothyroxine may be beneficial for RPL women if TPOAb + or SCH occurs. Future studies are needed to verify our findings.

Yu, Q., et al. (2019). "Letrozole versus laparoscopic ovarian drilling in clomiphene citrate-resistant women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials." Reproductive biology and endocrinology : RB&E 17(1): 17.
	The objective of this systematic review was to examine the literature and to compare the effectiveness of letrozole (LE) versus laparoscopic ovarian drilling (LOD) for the induction of ovulation in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). The PUBMED, Web of Science, and EMBASE databases were searched systematically for eligible randomized controlled trials (RCTs) from English language articles published from database inception to September 2018. Data were independently extracted and analyzed using the fixed-effects model or random-effects model according to the heterogeneity of the data. Four RCTs including 621 patients (309 in the LE group and 312 in the LOD group) met the inclusion criteria. There were no differences with regard to ovulation rate (relative risk [RR] 1.12; 95% confidence interval [CI] 0.93 to 1.34; P = 0.12, I 2 = 90%, 541 patients, three studies), pregnancy rate (RR 1.21; 95% CI 0.95 to 1.53; P = 0.12, I 2 = 0%, 621 patients, four studies), live birth rate (RR 1.27; 95% CI 0.96 to 1.68; P = 0.09, I 2 = 19%, 541 patients, three studies), and abortion rate (RR 0.7; 95% CI 0.3 to 1.61; P = 0.40, I 2 = 0%, 621 patients, four studies) between the two groups. These results indicated that LE and LOD appear to be equally effective in achieving live birth rate in patients with CC-resistant PCOS.

Yu, Q., et al. (2021). "Effectiveness and safety of aspirin combined with letrozole in the treatment of polycystic ovary syndrome: a systematic review and meta-analysis." Annals of Palliative Medicine 10(4): 4632-4641.
	Background: Meta-analysis was used to evaluate the efficacy and safety of aspirin combined with letrozole in the treatment of polycystic ovary syndrome (PCOS).; Methods: Through comprehensive searches of the China Knowledge Network (CNKI), the VIP database (VIP), the Wanfang database, the China Biomedical Database (CBM), PubMed, EMBASE, and the Cochrane Library, the clinical randomized controlled trials (RCTs) published on aspirin combined with letrozole in the treatment of PCOS were collected. According to the inclusion and exclusion criteria, the included studies were screened and quality evaluated, and RevMan 5.3 software was used for meta-analysis.; Results: A total of 10 RCTs and 948 patients with PCOS were included. Meta-analysis results showed that compared with letrozole monotherapy, aspirin combined with letrozole could significantly increase the thickness of the endometrium [MD=1.98, 95% CI: 1.63-2.34, P<0.00001], cervical mucus scores (MD =1.65, 95% CI: 1.32-1.98, P<0.00001), the ovulation rate (OR=3.50, 95% CI: 2.08-5.91, P<0.00001), the number of mature follicles (MD=0.65, 95% CI: 0.51-0.78, P<0.00001), and the pregnancy rate (OR=3.06, 95% CI: 2.28-4.12, P<0.00001), and significantly reduced the abortion rate (OR=0.20, 95% CI: 0.11-0.38, P<0.00001). There was no statistically significant difference in the incidence of adverse reactions between the 2 groups (OR=0.76, 95% CI: 0.44-1.32, P=0.33).; Conclusions: Aspirin combined with letrozole in the treatment of PCOS is safe and effective. Due to the limitations in the number and quality of the included studies, further verification with multi-center, large-sample, high-quality RCTs is still needed.

Yu, S., et al. (2022). "Clinical and Patient Reported Outcomes Pre- and Postsurgical Treatment of Symptomatic Uterine Leiomyomas: A12-Month Follow-up Review of TRUST, a Surgical Randomized Clinical Trial Comparing Laparoscopic Radiofrequency Ablation (LAP-RFA) and Myomectomy." Journal of Bone and Joint Surgery 77(5): 266-267.
	(Abstracted from J Minim Invasive Gynecol 2022; doi: 10.1016/j.jmig.2022.01.009) Uterine leiomyomas (ULs) affect a large population of women in the United States. Despite the high incidence of women with symptomatic ULs, the number of surgical procedures performed annually is fewer than 250,000.

Yu, S., et al. (2022). "Clinical and Patient Reported Outcomes Pre- and Post-Surgical Treatment of Symptomatic Uterine Leiomyomas: A 12-Month Follow-Up Review of TRUST, a Surgical Randomized Clinical Trial Comparing Laparoscopic Radiofrequency Ablation (LAP-RFA) and Myomectomy." Journal of Minimally Invasive Gynecology.
	STUDY OBJECTIVE: The objective of this study was to determine the efficacy, safety, and healthcare resource utilization of laparoscopic radiofrequency ablation (LAP-RFA) compared to myomectomy in patients with symptomatic uterine leiomyomas (ULs). DESIGN: This was a secondary analysis of the original post-market randomized, prospective, multi-center, longitudinal, comparative TRUST US trial in patients with symptomatic ULs. After the procedure, subjects were followed over a 12-month period. SETTING: Multi-center trial, including hospitals with or without an academic affiliation, surgery centers, and fertility centers performing outpatient procedures for uterine fibroids PARTICIPANTS: A total of 57 patients were randomized to either LAP-RFA (n=30) or myomectomy (n=27) INTERVENTIONS: LAP-RFA or myomectomy (laparoscopic or abdominal) MAIN OUTCOME MEASURES: The main outcome measures of this study were part of the secondary outcomes of the original TRUST trial. The primary outcome of this study was the reduction of UL symptoms and the improvement in patient reported outcomes (PRO) scores over time. Secondary outcomes included hospitalization post-procedure, length of stay, complications, reinterventions and recovery time. RESULTS: There was a significant improvement in UL symptoms at 3- and 12-months post-procedure within each treatment group and these improvements were similar between treatment groups. There was a significant reduction in UL symptoms per month between baseline and 12-months post-procedure for both LAP-RFA and myomectomy of 72% and 85%, respectively. A significant improvement was seen in all PRO scores over time for both groups. At 3- and 12-months post-procedure, the percentages of patients who were hospitalized in the LAP-RFA group were 74% and 49% lower than laparoscopic myomectomy at 3 and 12 months, respectively, with the 3-month difference being statistically significant. The length of hospital stay was significantly lower in the LAP-RFA group compared to Myomectomy (8.0 ± 5.7 hours vs 18.8 ± 14.6 hours; p<0.05). Doctors recommended taking significantly less time off before returning to work in the LAP-RFA group compared to myomectomy (10.3 ± 5.1 days vs 14.5 ± 5.4 days, p<0.05) and the total days until back to normal activity was significantly lower in the LAP-RFA group compared to myomectomy (16.3 ± 15.2 days vs 26.5 ± 15.9 days, p<0.05). CONCLUSION: The results from this 12-month follow up study suggest that LAP-RFA is a safe, effective, uterine-sparing alternative to laparoscopic myomectomy in the treatment of ULs. These data points build on previously published studies showing that LAP-RFA has lower healthcare resource utilization overall, including lower post-procedure hospitalization rate and length of stay. In clinical practice, LAP-RFA is a promising treatment approach to ULs for women. TRIAL REGISTRATION: NCT02163525 (https://clinicaltrials.gov/ct2/show/NCT02163525) STUDY TYPE: Interventional (clinical trial) ENROLLMENT: 114 participants ALLOCATION: Randomized INTERVENTION MODEL: Parallel assignment MASKING: None (open label) PRIMARY PURPOSE: Treatment STUDY START DATE: June 2014 ACTUAL PRIMARY COMPLETION DATE: July 2019 ESTIMATED STUDY COMPLETION DATE: June 2024 DATA REPOSITORY: https://pfgmed.box.com/v/TRUSTDataRep.

Yu, X. and L. He (2021). "Aspirin and heparin in the treatment of recurrent spontaneous abortion associated with antiphospholipid antibody syndrome: A systematic review and meta-analysis." Experimental and Therapeutic Medicine 21(1): 57.
	The present study aimed to review relevant, randomized, controlled trials in order to determine the effects of aspirin and heparin treatment on recurrent spontaneous abortion (RSA) in women with antiphospholipid syndrome (APS). Previous relevant studies were identified using PubMed, Cochrane, Embase, CNKI, VANFUN and VIP by retrieving appropriate key words. Additionally, key relevant sources in the literature were reviewed and articles published before May 2019 were included. The 22 selected studies included 1,515 patients in the treatment group and 1,531 patients in the control group. These previous studies showed that heparin and aspirin significantly improved live birth rate when compared with treatments using intravenous immunoglobulin, aspirin alone or aspirin combined with prednisone. Moreover, heparin and aspirin greatly increased the birth weight compared with placebo and improved vaginal delivery relative to intravenous immunoglobulin. The gestational age at birth was significantly higher in the heparin and aspirin group compared with the placebo group and the incidence of intrauterine growth restriction was lower in the heparin and aspirin group compared with the placebo group. Furthermore, heparin and aspirin markedly reduced the incidence of miscarriage compared with the aspirin group and the placebo group, and the incidence of pre-eclampsia was lower in the heparin and aspirin group than the placebo group. Thus, heparin and aspirin could be further examined for the treatment of RSA in women with APS. (Copyright: © Yu et al.)

Yu, X., et al. (2022). "Local Estrogen Therapy for Pelvic Organ Prolapse in Postmenopausal Women: A Systematic Review and Meta-Analysis." Iranian Journal of Public Health 51(8): 1728-1740.
	BACKGROUND: The prevalence of pelvic organ prolapse (POP) is expected to increase in the next few decades, imposing a substantial medical burden. The effect of local estrogen therapy (LET) on POP in postmenopausal women is still controversial; therefore, we aimed to provide reliable evidence to address this issue from the perspective of vaginal health and quality of life (QoL). METHODS: We searched in the PubMed, the Web of Science, Embase and the Cochrane Library databases for eligible RCTs from beginning to Apr 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in our study. RESULTS: Seven RCTs(n=570) were included. No significant improvement of the epithelial thickness (SMD=1.38, 95%CI -0.54 to 3.31, P=0.16) or vaginal pH (SMD=-0.98, 95%CI -2.65 to 0.69, P=0.25) after LET compared with the control. A slight increase was observed in the VMI (MD=16.58, 95%CI 1.14 to 32.02, P=0.04). Regarding QoL, no significant differences between the estrogen group and the control group in PFIQ-7 (6m: MD=3.60, 95%CI -3.13 to 10.33, P=0.29; 12m: MD=3.53, 95%CI -3.35 to 10.41, P=0.31), PISQ-12(6m: MD=0.62, 95%CI -0.73 to 1.98, P=0.37; 12m: MD=0.36, 95%CI -1.06 to 1.77, P=0.62), or PGI-I (6m: RR=0.99, 95%CI 0.92 to 1.07, P=0.88; 12m: RR=1.01, 95%CI 0.95 to 1.07, P=0.72) score. Moreover, no more specific adverse events (AEs) (RR=1.11, 95%CI 0.84 to 1.48, P=0.46) were observed in the interventional group. CONCLUSION: Not find LET caused either a significant improvement in vaginal health and QoL or more AEs.

Yu, X., et al. (2021). "Effects of eras combined with holistic nursing in elderly patients with ovarian cancer." International Journal of Clinical and Experimental Medicine 14(2): 961‐970.
	Objective: To observe the effect of enhanced recovery after surgery (ERAS) combined with holistic nursing on the nursing quality of elderly patients with ovarian cancer. Methods: A total of 94 elderly patients with ovarian cancer who were admitted to our hospital were randomly divided into two groups, with 47 cases in each group. The control group was given routine nursing, while the intervention group was given holistic nursing with ERAS (mainly including health education, rational fasting, early postoperative activities and other methods). The recovery of gastrointestinal function (first exhaust, defecation, time of getting out of bed and motilin level (MTL) before and after intervention), psychological state (SAS, SDS score), pain degree (VAS score), complications, nursing quality score, hospitalization time and nursing satisfaction were compared between the two groups. Results: After intervention, the MTL level of the two groups decreased, but the MTL level of the intervention group was higher than that of the control group (P<0.05). The first time of exhausting, defecating and getting out of bed in the intervention group was earlier than that of the control group, and the hospitalization time was shorter than that of the control group (P<0.05). After intervention, SAS and SDS scores of both groups decreased, and those of the intervention group was lower than those of the control group (P<0.05). At 6 h and 12 h after operation, VAS scores in the intervention group were lower than those in the control group (P<0.05). There was no significant difference in the incidence of complications between the intervention group and the control group (P>0.05). The scores of nursing quality and nursing satisfaction in the intervention group were higher than those in the control group (P<0.05). Conclusion: ERAS combined with holistic nursing intervention in elderly patients with ovarian cancer after operation can effectively promote the recovery of gastrointestinal function, relieve bad mood, relieve pain, improve nursing quality and encourage patients to recognize nursing service.

Yu, X. and Y. Min (2022). "Meta-analysis of the efficacy of Warming Acupuncture in treating chronic pelvic inflammatory disease."
	Review question 温针治疗慢性盆腔炎症的效果如何？随机对照试验的荟萃分析。 Searches 计算机检索中文期刊全文数据库（CNKI）、万方学术期刊全文数据库（万方）、VIP中文科技期刊数据库（VIP）、中国生物医学文献数据库（CBM）、PubMed、Cochrane图书馆、Embase、Web of Science等中英文数据库。检索时间截止到2022年10月。 Types of study to be included 随机对照试验（盲法和分配隐藏法） Condition or domain being studied 慢性盆腔炎症往往是由急性盆腔炎症引起的，不能得到彻底的治疗，患者的体质差也是病程延误的原因，使病情更加顽固。流行病学调查显示，15个省市妇女慢性盆腔炎症发病率为4.1%。目前慢性盆腔炎症的主要治疗方法是抗生素和手术治疗，但大多数人容易复发，不良反应较多。针灸、中药煎剂、中药灌肠、中药熏蒸洗涤都包含在中医治疗中。特别是温针具有增经散寒、疏通经络、补正祛邪、消炎免疫调节等功能，还能改善血流动力学。 Participants/population 符合《中新妇产科临床研究指导原则》、《中医妇科妇产科》、《妇产西医结合妇产科》等诊断标准的慢性盆腔炎症患者，必须在论文中注明诊断依据来源 Intervention(s), exposure(s) 治疗组单独使用温针或温针结合基础治疗 Comparator(s)/control 对照组采用温针以外的其他疗法或基础治疗（治疗组和对照组均进行基础治疗） Main outcome(s) 总有效率、彩色超声盆腔质量直径、视觉模拟量表 Additional outcome(s) 不 Data extraction (selection and coding) After literature retrieval by two researchers, the literature was independently screened and the data was extracted according to the inclusion and exclusion criteria. According to the inclusion and exclusion criteria, two researchers extracted information about the first author, year of publication, study subject age, disease duration, intervention measures, outcome indicators and other information, and cross-checked the extracted data after completion. In case of differences, both parties shall discuss or decide jointly by a third party with researchers with senior titles. Risk of bias (quality) assessment 两位研究者根据Cochrane手册推荐的偏倚风险评估工具进行偏倚风险评估，主要包括随机序列的产生、分配隐藏、受试者和研究人员的盲性、结局评价的盲性、结局资料不完整、选择性报告等7项偏倚内容。制作：高风险，低风险，每个条目判断不明确。

Yu, Y., et al. (2022). "Efficacy and safety of oral Chinese patent medicines in treatment of polycystic ovary syndrome: A network Meta-analysis." Chinese Traditional and Herbal Drugs 53(23): 7477-7490.
	Objective To evaluate the efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in the treatment of polycystic ovary syndrome (PCOS) by frequency network Meta-analysis. Methods The randomized controlled trials (RCTs) on oral Chinese patent medicines in the treatment of PCOS were retrieved from CNKI, Wanfang, VIP, SinoMed, Duxiu, PubMed, Embase, Cochrane Library, Web of Science, Ovid and Scopus databases from the time of database establishment to May 2022. Two researchers independently extracted literature data according to inclusion and exclusion criteria, the quality of the included RCTs was evaluated according to the Cochrane bias risk assessment tool, and the data was analyzed by RevMan5.4 and Stata/SE 17.0. Results A total of 32 RCTs were included, involving nine kinds of oral Chinese patent medicines and 3534 patients. The results of the network Meta-analysis showed that the top three optimal medication regimens in reducing serum testosterone levels were conventional western medicine respectively combined with Kuntai Capsules (), Danshentong Capsules (), and Peikun Pills (). The top three optimal medication regimens in reducing luteinizing hormone levels were conventional western medicine respectively combined with Danshentong Capsules, Peikun Pills, and Qilin Pills (). The top three optimal medication regimens in improving insulin resistance were conventional western medicine respectively combined with Bailing Capsules (), Honghua Xiaoyao Tablets (), and Kuntai Capsules. The top three optimal medication regimens in reducing blood triglycerides levels were conventional western medicine respectively combined with Danshentong Capsules, Bailing Capsules, and Dingkun Dan (). In terms of safety, the top three optimal medication regimens were conventional western medicine respectively combined with Fukezaizao Capsules (), Dingkun Dan, and Fufang Xuanju Capsules (). Conclusions The oral Chinese patent medicines combined with conventional therapy can effectively improve the clinical efficacy of the treatment of PCOS, with good safety. However, limited by the quality and quantity of literature included in this study, large samples and high-quality trials are still needed to further verify the results.Copyright © 2022 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Yu, Y., et al. (2022). "Minimally invasive surgery and abdominal radical hysterectomy in patients with early-stage cervical cancer: A meta-analysis." International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 157(2): 255-264.
	Objective: To compare risk of recurrence and death related to minimally invasive surgery (MIS) and abdominal radical hysterectomy (ARH) in early-stage cervical cancer (CC) patients.; Methods: All relevant literatures in databases were retrieved from the built time of databases to October 2020. Observational studies comparing MIS and ARH in early-stage CC patients were involved. Newcastle-Ottawa Scale was used for quality assessment, including studies with a score of at least 6. Main outcomes involved overall survival (OS) and disease-free survival (DFS).; Results: Twenty-two studies were involved, including 14 894 patients, among which 7213 (48.6%) underwent MIS. The OS (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.03-1.43) and DFS (HR 1.25, 95% CI 1.07-1.42) of patients undergoing MIS was obviously shortened compared with those of patients undergoing ARH. Subgroup analysis revealed that OS (HR 1.42, 95% CI 1.10-1.74) and DFS (HR 1.46, 95% CI 1.18-1.74) of patients with a tumor ≥2 cm in diameter were significantly reduced by MIS.; Conclusion: Overall survival and DFS after MIS for early-stage CC treatment were worse than those after ARH, especially for patients with a tumor ≥2 cm in diameter. (© 2021 International Federation of Gynecology and Obstetrics.)

Yu, y. and C. yanhua (2022). "Enhanced Recovery After Surgery (ERAS) reduces hospital costs and improve clinical outcomes in endometriotic diseases: a systematic review."
	Review question Comparation of enhanced recovery after surgery (ERAS) against the conventional care in endometriotic diseases. Is enhanced recovery more effective than conventional care? In comparation with the conventional care, does enhanced recovery reduce length of stay and health costs without increasing complications and readmissions? Searches The data sourse come from:CINAHL Complete (EBSCO)、MEDLINE (Ovid)、EMBASE (Ovid)、PubMed、Web of Science 、Cochrane、PsycINFO、和 Emcare (Ovid) and CNKI、Wanfangdata、CQVIP. Search language:English and Chinese. Keywords used were: "Adenomyosis"[MeSH], “endometri*", and "Fast-Track", "Fast Track", "Enhanced recovery", "Rapid Recovery", "Early Recovery" , "accelerated rehabilitation", "rapid rehabilitation", "ERAS" ,"Accelerated Recovery". Types of study to be included randomized controlled trial . Condition or domain being studied Enhanced recovery is described as a protocol related to preoperative, intraoperative, and postoperative care. Current studies on ERAS and traditional perioperative protocols at home and abroad.There are few clinical studies on the application of contrast in gynecological surgery, most outcome indicators not complete, the reference significance is limited. Participants/population: inclusion criteria: randomized controlled trials, studies that compare enhanced recovery with conventional care in endometriotic diseases，articles in english, chinese, outcomes (Anal exhaust time, postoperative complications, average stay, health costs...) exclusion criteria:The research data is not complete, repetitive research. Intervention(s), exposure(s): Enhanced Recovery. The enhanced recovery is described as a protocol related to preoperative, intraoperative and postoperative care. The objective is to improve patient recovery, provide early discharge and reduce health care costs without increasing complications. Comparator(s)/control: Routine treatment and nursing care. Main outcome(s): Hospital stays. Additional outcome(s): Postoperative complications, anal recovery time, hospitalization cost, readmission rate.

Yu, Z. and W. Chunyu (2023). "Efficacy and Safety of Different Subsequent Therapies After Fertility Preserving Surgery for Endometriosis&#xff1a;A Network Meta-AnalysisEfficacy and Safety of Different Subsequent Therapies After Fertility Preserving Surgery for Endometriosis&#xff1a;A Network Meta-Analysis."
	Review question To evaluate the efficacy and safety of dienogest，deuprolide，danazol，gestrinone，mifepristone and LNG-IUS in relieving the symptoms and delaying the recurrence of endometriosis cysts after fertility preserving surgery for endometriosis. Searches PubMed，the Cochrane Library，Web of Science，EMBase，CNKI，VIP，CBM，WanFang Data databases Types of study to be included The application of dinorgestrel, lepraline, Danazole, pregntrienone, mifepristone and levonorgestrel intrauterine sustained-release system (LNG-IUS) in drug therapy after fertility preservation surgery in patients with EMT has been published at home and abroad. It is not limited to whether the blind method is implemented, whether the allocation is hidden, and whether there are cases lost to follow-up; There is no limitation on study location and publication period. Condition or domain being studied endometriosis Participants/population inclusion:Patients who underwent fertility preservation surgery (removal of all visible lesions, release of adhesion, preservation of uterus, preservation of one/both sides/at least part of ovaries) and were histologically diagnosed as having EMT after surgery were limited to 20 to 40 years of age, regardless of nationality, course of disease, and fertility requirements. exclusion:Women younger than 20 and older than 40. Intervention(s), exposure(s) The experimental groups were treated with dinorgestrel, lepraline, danazole, pregntrienone, mifepristone or LNG-IUS as follow-up drugs after surgery. Comparator(s)/control Control group: Placebo or no medication. Main outcome(s) Effective rate: the number of cases/total cases of remission (no symptoms, no pelvic mass formation) and improvement (relief of symptoms, no positive signs, no pelvic mass formation). Additional outcome(s) (1) Recurrence rate: the number of cases/total cases of secondary dysmenorrhea reoccurring or progressive aggravation of pelvic mass found by auxiliary examination; (2) Pregnancy rate: the number of pregnant patients with fertility requirements/the number of patients with fertility requirements; (3) Adverse reaction rate: the number of cases of adverse drug reaction symptoms/total cases.

Yuan, B. C., et al. (2019). "[Bushen Huoxue herbal medicine in subfertile women with polycystic ovary syndrome: a Meta-analysis]." Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 44(6): 1080-1086.
	Meta-analysis of randomized controlled trials( RCTs) was conducted to clarify the effect of Bushen Huoxue herbal medicine in subfertile women with polycystic ovary syndrome. Databases including CNKI,Wan Fang,VIP,Sino Med,PubMed,EMbase,the Cochrane Library were searched until September,2018. Two reviewers independently assessed study eligibility,extracted data,and evaluated the risk of bias for included trials. Meta-analysis used Review Manager 5. 3 software. Seven RCTs( n = 634) were included.RESULTS: of Meta-analysis indicated that,Bushen Huoxue herbal medicine had advantages on increasing pregnancy rate,lowering LH,T and INS. Bushen Huoxue herbal medicine were not clear on increasing ovulation rate,increasing FSH. No serious adverse reaction appearing from Bushen Huoxue herbal medicine was reported in the including researches. The current Meta-analysis showed a promising effect of Bushen Huoxue herbal medicine in subfertile women with polycystic ovary syndrome,but the quality of current evidence was low and possible publication bias.

Yuan, J., et al. (2022). "Ovarian protection and safety of gonadotropin-releasing hormone agonist after cervical cancer surgery: systematic review and meta-analysis." Annals of Translational Medicine 10(7): 409.
	Background: This meta-analysis was performed using Stata (15.0), and sought to systematically evaluate the domestic application value of the gonadotropin-releasing hormone agonist (GNRH-a) after cervical cancer, and explore its protective effect on the ovaries during chemotherapy. In many studies, the effectiveness and safety of GNRH-a are not consistent, and there is great controversy. Therefore, it is very important to systematically evaluate the protection and safety of GNRH-a after cervical cancer surgery.; Methods: PubMed, Cochrane Library, and Web of Science databases were systematically searched to retrieve articles on domestic trials examining the use of GNRH-a treatment in cervical cancer patients, published from January 2014 to January 2021, which were reviewed according to the inclusion and exclusion criteria of this study. The meta-analysis of the included study data was conducted using Stata 15.0.; Results: In total, 10 articles were included in the meta-analysis, comprising 579 ovarian-reserved cervical cancer subjects, all of whom received 4-6 standardized courses of PC (Paclitaxel + Cisplatin) chemotherapy. The following statistically significant differences were found: bovine follicle stimulating hormone [odds ratio (OR) =1.82, 95% confidence interval (CI): 1.38-2.38; P<0.0001], bovine estrogen 2 (OR =2.39, 95% CI: 1.69-3.37; P<0.00001), anti-Mullerian hormone (OR =2.39, 95% CI: 1.71-3.34; P<0.00001), and bovine antral follicle count (OR =2.11, 95% CI: 1.49-2.99; P<0.0001); but there is no statistically significant difference incidence of coincidences (OR =0.80, 95% CI: 0.49-1.31; P=0.38).; Conclusions: The use of GNRH-a in cervical cancer patients receiving the PC chemotherapy regimen plays a significant role in protecting ovarian function.; Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-928/coif). The authors have no conflicts of interest to declare. (2022 Annals of Translational Medicine. All rights reserved.)

Yuan, L., et al. (2021). "The function of metformin in endometrial receptivity (ER) of patients with polycyclic ovary syndrome (PCOS): a systematic review and meta-analysis." Reproductive biology and endocrinology : RB&E 19(1): 89.
	Background: This meta-analysis summarizes evidence from studies using metformin (Met) to improve endometrial receptivity (ER) in women with PCOS.; Methods: Following the PRISMA protocol, we conducted a comprehensive search of academic literature from various databases, including PubMed, EMbase and Cochrane libraries. Studies published in English before Jan 27, 2021, were recruited for primary screening. Data on endometrial thickness (EMT), endometrial artery resistance index (RI), clinical pregnancy rate (CPR) and miscarriage rate (MR) were extracted and analyzed.; Results: Sixty-two eligible studies that included 6571 patients were evaluated in this meta-analysis. Primary indicators are EMT and endometrial aetery RI; secondary indicators include the clinical pregnancy rate and miscarriage rate. Metformin significantly increased EMT (SMD = 2.04, 95% CI (0.96,3.12),P = 0.0002) and reduced endometrial artery RI compared to the non-Met group (SMD = - 2.83, 95% CI: (- 5.06, - 0.59), P = 0.01). As expected, metformin also improved CPR and reduced MR in PCOS patients as a result, clinical pregnancy rate (risk ratio [RR] = 1.26, 95% CI: 1.11-1.43, P = 0.0003), and miscarriage rate (RR = 0.73, 95% CI:0.58-0.91, P = 0.006).; Conclusion: Metformin may improve endometrial receptivity (ER) in PCOS patients by increasing EMT and reducing endometrial artery RI. However, the level of most original studies was low, with small sample sizes. More large-scale, long-term RCTs with rigorous methodologies are needed.

Yuan, M., et al. (2022). "Highlighting the Mechanistic Relationship Between Perinatal Depression and Preeclampsia: A Scoping Review." Women's health reports (New Rochelle, N.Y.) 3(1): 850-866.
	BACKGROUND: Although there is scientific literature supporting an association between depression and preeclampsia (PE), little is known about the underlying mechanistic pathways that may explain these observed associations. Thus, this study aimed to outline the relationship between depression and PE, and to highlight the underlying cardiovascular and metabolic risk factors that are common to both. METHODS: A scoping review of the literature was conducted in Medline, Scopus, and Web of Science. RESULTS: From 706 articles initially identified, 23 articles met the inclusion criteria and were included in this review. Although some studies reported a positive association between PE and postpartum depressive symptoms, challenges comparing different methodologies, measurement instruments and when measurements were administered, and patient populations do not permit a decisive conclusion. In addition, very few studies addressed potential underlying mechanisms that may be contributing to observed associations; thus, a secondary search was conducted to identify cardiovascular and metabolic risk factors that are common to both depression and PE. CONCLUSION: The cardiovascular and metabolic risk factors (i.e., increased inflammation and oxidative stress and decreased vascular and endothelial function) common to both depression and PE suggest that these factors may contribute as underlying mechanisms in both conditions. These similarities underscore the importance to better understand these mechanisms so preventative and therapeutic strategies could be developed to improve maternal health.

Yuan, M., et al. (2022). "Effect of physical activity on prevention of postpartum depression: A dose-response meta-analysis of 186,412 women." Frontiers in Psychiatry 13: 984677.
	Background: Physical activity (PA) is considered a favorable preventive intervention for postpartum depression (PPD), but evidence defining a corresponding dose-response relationship is lacking. This meta-analysis was conducted to assess the protective effects of PA on PPD and define a potential dose-response relationship between them.; Methods: PubMed, Medline, Embase, and Web of Science were searched from 1968 to May 2022. Only randomized control trials (RCTs) and prospective studies were considered, and the PICOS tool was used to identify eligible articles based on the inclusion and exclusion criteria. Effect-size estimates were unified as odds ratio (OR) and 95% confidence interval (CI). We calculated the ORs and their 95% CI for studies that did not report them using the Practical Meta-Analysis Effect Size Calculator.; Results: A total of 23 studies were eligible, including 14 RCTs and 9 prospective cohort studies. The overall analysis showed a statistically significant positive association between PA and PPD prevention (adjusted OR = 0.73; 95% CI: 0.61-0.87; P < 0.001). Subgroup analyses indicated that studies conducted in Europe demonstrated a significant correlation between PA and reduced PPD risk (adjusted OR = 0.85, 95% CI: 0.76-0.95, P = 0.004). Concerning PA type, sports activity was associated with relieving PPD symptoms (adjusted OR = 0.89, 95% CI: 0.78 to 1.00, P < 0.001), while work (adjusted OR = 1.05, 95% CI: 0.37-2.97, P = 0.065) and household activities (adjusted OR = 1.16, 95% CI: 0.89-1.52, P = 0.986) contributed to a greater risk of PPD. Our dose-response analysis revealed a reverse J-shaped trend between ascending PA duration and PPD incidence.; Conclusion: This meta-analysis identified PA as a potential intervention to reduce the risk of PPD. The dose-response analysis revealed that at least 90 min of PA per week could efficiently decrease the risk of PPD.; Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022335731.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yuan, Chen, Chen, Wan, Luo, Zhang, Nan, Bi and Liang.)

Yuan, P., et al. (2019). "Efficacy of low-intensity extracorporeal shock wave therapy for the treatment of chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta-analysis." Neurourology and Urodynamics 38(6): 1457-1466.
	Aims: Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been applied in urolithiasis and some chronic diseases. We performed a systematic review and meta-analysis to assess the efficacy of Li-ESWT for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).; Methods: A comprehensive search of MEDLINE, Web of Science, EMBASE, and the Cochrane Library to January 6, 2019 was performed for randomized controlled trials (RCTs) reporting on patients with CP/CPPS treated with Li-ESWT compared with the sham group. Outcomes were evaluated based on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). The quality assessment of included studies was performed by the Cochrane System.; Results: Six publications involving five RCTs with 280 patients were assessed in this review. NIH-CPSI total score, pain domain and quality of life (QOL) were significantly better in the Li-ESWT group than those in the control group at the endpoint (P < 0.00001, P = 0.003, and P < 0.00001), 4 weeks (P < 0.00001, P = 0.0002 and P < 0.00001) and 12 weeks (P < 0.00001, P < 0.00001, and P = 0.0002) after the treatment. For urinary score, significant difference existed at 12 weeks after the treatment (P = 0.006). At 24 weeks after treatment, there was no significant difference between the two groups in NIH-CPSI total score (P = 0.26), pain domain (P = 0.32), urinary score (P = 0.07), and QOL (P = 0.29).; Conclusions: Li-ESWT showed great efficacy for the treatment of CP/CPPS at the endpoint and during the follow-up of 4 and 12 weeks, though the efficacy of 24-week follow-up was not significantly different due to insufficient data. Generally, Li-ESWT is a promising minimal invasive method for the treatment of CP/CPPS. (© 2019 Wiley Periodicals, Inc.)

Yuan, S., et al. (2019). "Comparison of the efficacy and safety of phloroglucinol and magnesium sulfate in the treatment of threatened abortion: A meta-analysis of randomized controlled trials." Medicine 98(24): e16026.
	Background: To compare the clinical efficacy and safety of phloroglucinol (PHL) and magnesium sulfate (MS) in the treatment of threatened abortion through systematic review.; Methods: Foreign databases, such as the Cochrane Library, PubMed and EMBASE, and Chinese databases, including the China Biology Medicine disc (SinoMed), China National Knowledge Infrastructure (CNKI), Chongqing VIP (VIP) and WanFang Data, were searched. Published randomized controlled trials (RCTs) documents obtained from these databases were included if they were associated with the research objective. The search timeframe was from the beginning of the establishment of each database to May 2018. Document selection, data abstraction and document quality evaluation were independently performed by 2 investigators. A combined analysis of the data was performed for those documents that fulfilled the study requirements; Rev Man 5.3 and Stata 12.0 software were used to compare and analyze the 2 drugs in terms of the total effective rate (TER), rate of adverse events, time required to relieve uterine contractions, onset time, time of complete relief of uterine contraction symptoms, medication duration and length of hospital stay.; Results: A total of 21 RCT trials were included in the present research, according to the inclusion criteria. However, the quality of the included studies was low. The meta-analysis suggested that the TER and drug onset time of PHL were higher than those for MS, while the rate of adverse events, the time required to relieve uterine contractions, time to complete relief of uterine contraction symptoms, drug continuous treatment time and length of hospital stay were shorter than those for MS.; Conclusion: The clinical efficacy of PHL is better than that of MS, and PHL obviously results in fewer adverse reactions than MS. However, due to poor quality of evidence, high quality, multi-center RCTs with large samples are required for further verification.

Yuan, Y., et al. (2022). "Nimotuzumab combined with chemoradiotherapy for the treatment of cervical cancer: A meta-analysis of randomized controlled trials." Frontiers in Oncology 12: 994726.
	Objectives: To assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer.; Methods: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis.; Results: A total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups.; Conclusions: Nimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yuan, Chen, Fang, Guo, Sun, Yu, Guo and Xin.)

Yuan, Y., et al. (2023). "Cognitive behavioral stress management is an effective intervention to relieve anxiety and depression, improve the quality of life in patients with cervical cancer." Irish Journal of Medical Science.
	Background: Cognitive behavioral stress management (CBSM) modifies individuals' maladaptive cognition and improves their ability in managing stress. The present study was to inquire about the utility of CBSM in mental health and quality of life in patients with cervical cancer.; Methods: Totally, 172 postoperative cervical cancer patients were randomly classified into CBSM (N=86) and normal care group (N=86) to receive 8-week CBSM and normal care, correspondingly. Self-rating anxiety/depression scale (SAS/SDS), EuroQol-5 dimensions (EQ-5D), EuroQol-visual analogue scale (EQ-VAS), and quality of life questionnaire-core 30 (QLQ-C30) scores were evaluated at discharge (M0), 1 st month (M1), M3, and M6 after discharge.; Results: SAS scores at M6 (P=0.003), M1 (P=0.042), and M3 (P=0.010), and the proportion of patients with SAS-defined anxiety at M3 (P=0.040) and M6 (P=0.019) were reduced in CBSM group versus normal care group. SDS scores at M3 (P=0.020) and M6 (P=0.016), and the proportion of patients with SDS-defined depression at M6 (P=0.036) was descended in CBSM group versus normal care group. EQ-VAS score at M1 (P=0.044), M3 (P=0.014), and M6 (P=0.002) were increased, while EQ-5D score at M3 (P=0.030) was descended in CBSM group versus normal care group. Meanwhile, QLQ-C30 global health status score at M1 (P=0.046), M3 (P=0.037), and M6 (P=0.007), QLQ-C30 function score at M3 (P=0.033) and M6 (P=0.016) were ascended, but QLQ-C30 symptom score at M3 (P=0.042) was declined in CBSM group versus normal care group.; Conclusion: CBSM is an effective intervention for decreasing anxiety and depression, and improving quality of life in patients with cervical cancer. (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Yuanzhuo, C., et al. (2021). "Sacrospinous ligament fixation vs uterosacral ligaments suspension for pelvic organ prolapse: a systematic review and meta-analysis."
	Review question Is sacrospinous ligament fixation as effective as uterosacral ligaments suspension for patients with pelvic organ prolapse? Searches Following search headings were used: “uterine prolapse”, “vaginal prolapse”, “pelvic organ prolapse”, “sacrospinous ligament fixation”, “Sacrospinous ligament attachment”, “sacrospinous ligament colpopexy”, “uterosacral ligament suspension”, “USL attachment”, “USL fixation”, “uterosacral colpopexy”, “surgical success”, “anatomical success”, “complication”, “recurrence” and “reoperation”. Types of study to be included Study types were randomized controlled trials or non-randomized controlled trials including retrospective cohort and prospective cohort. Condition or domain being studied Pelvic organ prolapse (POP) is a common health problem worldwide. Millions of women suffered such prolapse as a result of increasing aging population and obesity rates1. POP has a negative influence on women’s quality of life and adversely affects the psychological condition and sexual experience2. Reportedly, the lifetime risk of undergoing surgical treatment for pelvic organ problem is between 11 and 19%3. Participants/population Patients with pelciv organ prolapse. Intervention(s), exposure(s) two groups, one is patients have undergone sacrospinous ligament fixation. Comparator(s)/control two groups, another is patients have undergone uterosacral ligament suspension. Context Studies were published in English. Outcome indicators included at least on of following items: surgical success rate, anatomical success rate, complication rate and recurrence rate. Exclusion criteria were: 1) Patients with POP have undergone related surgery before.; 2) Mesh was used during the operation; 3) Lack of evaluation indicators required for analysis. Main outcome(s) Primary outcomes included: anatomical success rate, recurrence, surgical success rate and total complication rates. Measures of effect Relative risks. Additional outcome(s) Different types of complications. Measures of effect Relative risks. Data extraction (selection and coding) Two reviewers browsed the included articles’ title and abstract to extract data by using a pre-designed form. Any disagreement during data extraction was resolved by reaching a consensus between two reviewers or by the help of a third reviewer. The pre-designed form included the following information: title, authors, years of publication, sample size, study type, randomization, the demographic characteristics of the participants, outcome measurements (anatomical success rate, subjective success, complications) and their results. Risk of bias (quality) assessment We assess the risk of bias of included RCT studies using guideline suggested by Cochrane. Retrospective studies are evaluated by GRADE guidelines. Strategy for data synthesis Study results were meta-analyzed using Mantel-Haenszel fixed effects model. If the I² values more than 50%, random effects model was used. The dichotomous results from the original study were pooled to obtain the risk ratios (RR) and corresponding 95% confidence intervals (CI) for the resulting events. For continuous variables, we use mean and standard deviation to combine statistics. The I² reported as an indicator was used to assess the proportion of total variability due to heterogeneity combined study. I² values of 25%, 50%, and 75% generally denote a small, moderate, and high proportion of variability, respectively. If any outcomes had high heterogeneity, sensitivity analysis would be applied to find the source of heterogeneity. All analysis was implemented by REVIEW MANAGER 5.4 and GRADE profiler software. Analysis of subgroups or subsets Subgroup analysis stratified by the duration of follow up was also conducted. Publication bias was shown on funnel Plots only if more than seven studies were included.

Yue, G., et al. (2023). "Neoadjuvant Chemotherapy Followed by Surgery compared with Concurrent Chemoradiotherapy in Patients with FIGO Stage ⅠB2-ⅡB Cervical Cancer: a Meta-analysis."
	Review question This study will compare the efficacy and safety between neoadjuvant chemotherapy followed by surgery and concurrent chemoradiotherapy for treatment of patients with cervical cancer. Searches The electronic databases of PubMed, Embase, Web of Science, and Cochrane will be systematically searched to screen the relevant studies . In addition, the references included in the searched literatures and related reviews will also be searched to prevent eligible articles from being omitted. The search terms will included (1) “Cervical cancer” or “Uterine Cervical Neoplasms”; and (2) “Chemoradiotherapy”or “Chemo-Radiotherapy”. Types of study to be included Retrospective cohort study, RCT Condition or domain being studied Cervical cancer is the second most common malignant tumor in women and has become a major public health problem worldwide. In developing countries, more than 80% of patients with cervical cancer are diagnosed at an advanced stage, which seriously affects the prognosis of the sufferers. Since 2000, concurrent chemo radiotherapy (CCRT) is recommended as the standard treatment for LACC in some countries, which has been demonstrated to prolong the survival by approximately 50% compared with radiotherapy (RT) alone. However, a meta-analysis revealed that there were still 25% to 40% of patients with LACC experiencing relapse and the time to metastases at 5 years was also not significantly improved after CCRT compared with RT, implying the necessity to explore more effective therapeutic strategies.Neoadjuvant chemotherapy (NACT) followed by radicalsurgery (RS) has been extensively explored over the past decade as it could reduce the requirement of postoperative radiotherapy and thus improve the prognosis.NACT can shrink tumor size and hence transform inoperable into radically resected tumors. Participants/population cervical cancer patients Intervention(s), exposure(s) [1 change] neoadjuvant chemotherapy followed by surgery (NACT-S） Comparator(s)/control [1 change] concurrent chemoradiotherapy (CCRT) Main outcome(s) overall survival (OS), disease-free survival(DFS) Additional outcome(s) No Data extraction (selection and coding) Data extraction will also independently be carried out by two researchers based on preestablished forms. OS and DFS will be taken as the primary objective. Basic characteristics (including author, publication year, country, design, FIGO stage, NACT method, and follow-up time from studies that met the inclusion criteria) will be extracted. If the OS or DFS data in the study could not be extracted directly, Engauge Digitizer 4.1 will be used to extract the corresponding data through Kaplan-Meier survival curves. The quality of the included studies in this meta-analysis will be evaluated according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions in Chapter 8. Risk of bias (quality) assessment The quality of eligible studies will be evaluated according to the Newcastle-Ottawa Scale (NOS), which comprises eight points with three aspects: selection, comparability, and exposure. The scores of NOS system range from 0 to 9, and studies with 6 scores or more are considered as high quality Strategy for data synthesis In this meta-analysis, the HR and 95% CI will be pooled using Stata version 15.1 (StatCorp, College Station, TX, USA). Cochran's Q test combined with the I² test will be used to assess the statistical heterogeneity across the included cohorts. P-values<0.1 or I²≥50% indicates significant heterogeneity. A random-effect model will be used when substantial heterogeneity is observed; otherwise, a fixed-effect model will be used. Publication bias was evaluated using the Egger's test, and the trim-and-fill method. Analysis of subgroups or subsets Research type, Region, Neoadjuvant chemotherapy regimen, Follow-up time, Data sources

Yue, W., et al. (2022). "Metabolic Surgery on Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis." Frontiers in Endocrinology 13: 848947.
	Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical manifestations and related comorbidities of PCOS. However, the overall efficacy of metabolic surgery on PCOS remains uncertain. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of metabolic surgery on obese patients with PCOS. A systematic literature search for relevant studies was conducted on PubMed, Embase, Web of Science, and the Cochrane Library from inception to June 2021. Data extraction and quality evaluation were performed by three researchers, and RevMan 5.4 software was used to conduct the meta-analysis. A total of 14 studies involving 501 obese patients with PCOS were included. Incidence of PCOS in obese women ranged from 5.5% to 63.5% among the included studies. The results showed the incidence of abnormal menstruation decreased from 81% to 15% (OR=0.03, 95% confidence interval (CI): 0.01-0.08), while the incidence of hirsutism dropped from 71% to 38% (OR=0.21, 95% CI: 0.06-0.74). Serum total testosterone and free testosterone levels decreased by 25.92 ng/dL (MD = -25.92, 95% CI: -28.90- -22.93) and 2.28 ng/dL (SMD = -2.28, 95% CI: -3.67- -0.89), respectively. Sex hormone-binding globulin (SHBG) levels increased by 26.46 nmol/L (MD = 26.46, 95% CI: 12.97-39.95). Serum anti-Mullerian hormone (AMH) levels decreased by 1.29 ng/mL (MD = -1.29, 95% CI: -1.92- -0.66). Small sample size studies revealed that pregnancy rates ranged from 95.2% to 100% postoperatively. Metabolic surgery contributed to marked improvement of abnormal menstruation, hirsutism, and levels of free testosterone, total testosterone, SHBG, and AMH in patients with PCOS. Our findings indicate that patients with PCOS are expected to benefit from metabolic surgery, and could help potentially improve their reproductive outcomes. Metabolic surgery could thus be a new viable option for the clinical treatment of PCOS.; Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021251524.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yue, Huang, Zhang, Li, Liu, Zhao, Shu, Liu, Li and Liu.)

Yuehan, R., et al. (2023). "Acupuncture for the treatment of uterine fibroid: a systematic review and meta-analysis of randomised clinical trials."
	Review question Uterine fibroids are common diseases in women of childbearing age. The objective of this meta-analysis of randomized controlled trials was to assess the effectiveness and safety of acupuncture for treating uterine fibroids. Searches Four English-language databases and Two Chinese-language databases were searched from their inception through May 23, 2023 : China National Knowledge Infrastructure (CNKI), Wanfang Database for Chinese Technical Periodicals, PubMed, Web of Science, Embase and Cochrane Central Registry of Controlled Trials (CENTRAL). Types of study to be included All RCTs evaluating acupuncture treatment for uterine fibroids were considered. Condition or domain being studied Uterine fibroids, also known as leiomyomas are the most common benign tumors of the uterus, affecting 25-30% of women during their reproductive years. The incidence of uterine fibroids increases with age, with the highest rate around 50% in women between 40 to 50 years old. Uterine fibroids are benign tumors and rarely become malignant. The exact cause of uterine fibroids is still unclear, but hormonal imbalance, especially excessive estrogen, may be related to the development of fibroids. Uterine fibroids can cause symptoms such as heavy menstrual bleeding, and pelvic pain due to compression of adjacent organs, and may require surgical treatment in severe cases. Participants/population Women diagnosed with uterine fibroids were included. Diagnostic criteria for uterine fibroids:（1）Clinical symptoms: There may be menstrual changes, manifested as increased menstruation, prolonged menstruation, bleeding profusely, and shortened menstrual cycles, which can lead to secondary anemia. There may also be an increase in vaginal secretions or vaginal discharge. When a fibroid is large, it can compress the bladder, rectum, or ureter, resulting in corresponding compression symptoms.（2）Physical signs: manifested as enlarged uterus, spherical or irregular, or a mass connected to the uterus.（3）Imaging examination: There mainly include ultrasound and MRI examination. Patients with severe diseases such as cardiovascular, liver, kidney, and hematopoietic systems, or those with mental illness are excluded. Intervention(s), exposure(s) The types of acupuncture treatment included: traditional acupuncture, electroacupuncture, wrist-ankle acupuncture, abdominal acupuncture, warm acupuncture and moxibustion（A method of fixing moxa sticks on acupuncture needles which seen as a holistic form of therapy） and fire needle therapy.Trials evaluating acupuncture that made use of nonpenetrating point stimulation, such as acupressure and transcutaneous electrical nerve stimulation (TENS), were disregarded by the research team. Comparator(s)/control Studies with fake acupuncture, acupressure, no therapy, medicine, or massage as the control treatment were included.Trials comparing various acupuncture techniques were disqualified because it was impossible to assess the effectiveness of the control intervention. Main outcome(s) (1)Uterine fibroid volume;(2)Uterine volume Measures of effect For continuous outcomes, we plan to summarize all continuous outcome data using mean differences (MD) and its 95% confidence interval (CI). Additional outcome(s) (1) Quality of life measured using validated scales including The Uterine Fibroid Symptom and Health-Related Quality of Life(UFS-QOL), Symptom Check list 90(SCL-90) or other validated scales; (2) Estradiol levels during menstruation; (3) Hemorheological indicators, including plasma viscosity and red blood cell aggregation index; (4) The total effective rate, which related to the reduction of fibroid volume and the degree of symptom relief； (5)Safety of the acupuncture intervention including adverse events and withdrawals for any reason. Measures of effect For dichotomous outcomes, we plan to summarize all dichotomous outcome data using risk ratios (RR) and its 95% confidence interval (CI). For continuous outcomes, we plan to summarize all continuous outcome data using mean differences (MD) and its 95% confidence interval (CI). Data extraction (selection and coding) The two researchers or consultation with a third researcher. Two independent researchers will extract information, including: 1. General study characteristics (first author and publication year; sample size; location of study and trialsponsors); 2. Information relevant to Risk of bias; 3. Participants (diagnosis; age; sex; study exclusion criteria; and other important baseline characteristics); 4. Interventions (acupuncture, frequency/session/duration); 5. Outcomes (measured outcomes and their definitions, measurement time points; length of follow-up); 6. Results (all dichotomous and continuous results that relevant to our primary and secondary outcomes). Where possible, we plan to convert variables that can be reported in different metrics (e.g. treatmentresponse rate) to a common metric. If the study contained insufficient information, we tried to communicate. Risk of bias (quality) assessment Two reviewers will evaluate the included study according to the bias risk assessment tool recommended by Cochrane manual independently. A judgement of low-risk, high-risk and unclear-risk by assigning for eachresult. It consists of the following six aspects: 1. Selection bias; 2. Performance bias; 3. Detection bias; 4. Attrition bias; 5. Reporting bias; 6. Other biases. Strategy for data synthesis Rev Man 5.3 software provided by the Cochrane Collaboration Network was used for the meta-analysis. In this study, we choose random effects model for our analysis. The relative risk (RR) was used for the dichotomous variables, the mean difference (MD) was used for the continuous variables, and the 95% confidence interval (CI) was used for each effect quantity. If necessary, subgroup and sensitivity analyses will also be performed to analyze the source of any heterogeneity. Analysis of subgroups or subsets If the evidence of included studies is sufficient and appropriate, a predefined subgroup analysis will beconducted to assess the heterogeneity of different studies, including the following:1. Type of acupuncture;2. Types of treatment durations of acupuncture therapy (within 4 weeks, 4 weeks to 8 weeks, more than 8weeks, etc.)

Yueming, L., et al. (2021). "A systematic review of tuina for women with primary dysmenorrhea: A protocol for systematic review and meta-analysis."
	Review question We aid to test the effectiveness and safety of tuina on dysmenorrhea. Searches The following electronic databases will be searched from the respective dates of database inception to September 1st, 2021: The Cochrane Library, Web of Science, EMBASE, Springer, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the World Health Organization International Clinical Trials Registry Platform, the Chinese Scientific Journal Database, Wanfang database, and other sources. Types of study to be included Randomized controlled trials (RCTs) and blinded research, of relevance to the subject of interest only Condition or domain being studied The primary pain is mainly manifested as spasmodic pain in the lower abdomen before menstruation and menstruation, which is more common in adolescents and unmarried women. Participants/population Participants are female patients aged between 16 and 28 years, with primary dysmenorrhea. And they were excluded from organic disease. Intervention(s), exposure(s) Several types of massage will be included in the review: zang-fu massage, meridian massage, chiropractic massage, self-massage, etc Comparator(s)/control 1. no treatment or usual care 2. placebo 3. other interventions (e.g. acupuncture, cupping therapy, drugs and physical interventions) Main outcome(s) The main outcome will be pain measurements such as visual analogue scale (VAS), numeric rating scale (NRS), etc. Additional outcome(s) (1) The compliance in patients. (2) Serious adverse events (3) The degree of satisfaction with the treatment. Data extraction (selection and coding) We will extract data from the selected articles and discuss with experts to resolve any differences. The unified data were recorded in the Excel table, including the basic information of the classified study, the grouping method and the sample size. Participants were recorded with the mean age, plus and minus the mean value, standard deviation and percentage, etc. The intervention methods involved include treatment time, acupoints, techniques and therapeutic effects. Risk of bias (quality) assessment Two authors independently assess the studies that have been included in the systematic review across six domains: random allocation, allocation concealment, blinding (participants, intervention and outcome assessors), incomplete outcome data, selective outcome reporting and other sources of bias. The assessment will be done both at study and outcome level. For the risk of bias will be assessed through Cochrane's Risk-of-bias Tool for Randomized Trials (RoB 2). The risk of bias will be categorized as ‘low’(L), ‘unclear’(U) or ‘high’(H), indicating a low risk of bias,‘unclear’ indicating that the risk of bias is uncertain, and ‘high’ (H) indicating a high risk of bias. If the risk of bias is unclear, we will try to contact the trial authors for more data obtaining that will could help classify as ‘low’ or ‘high’. For incomplete outcome data, we will report the percentage and proportion of participants lost to follow-up. Funnel plots will be created to assess the reporting bias. Dyssymmetry funnel plot indicates high risk of reporting bias, while symmetric funnel plot indicates low risk. Two independent authors will be involved in the quality assessment. Third-party experts will be consulted when the assessment is in dispute. Strategy for data synthesis From the aspect of clinical research we will consider whether the meta-analysis is carried out. The clinical research includes the research designing of measurement methods, intervention methods, the length of treatment and whether the choice of the control group is same to determine. When a couple of good multiple homogeneity studies are included, we will perform meta-analyses with Review Manager 5.3.5. When I²<50%, the fixed effect model will be selected and the random-effects model will be selected I²>50%. If not, we will fail to implement meta-analysis. Analysis of subgroups or subsets If the heterogeneity is caused by clinical trials above-mentioned, subgroup analysis will be conducted and according to the outcomes of data synthesis detailed subgroup will be classified. Contact details for further information Yueming Lv 2082077873@qq.com Organisational affiliation of the review Shandong University of Traditional Chinese Medicine Review team members and their organisational affiliations Miss Yueming Lv. Shandong University of Traditional Chinese Medicine Fujie Jing. Shandong University of Traditional Chinese Medicine Huichao Feng. Shandong University of Traditional Chinese Medicine Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 30 September 2021 Anticipated completion date 31 March 2022 Funding sources/sponsors Shandong province Science and technology development program of Traditional Chinese Medicine (No. 2019-0053) Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Dysmenorrhea; Female; Humans; Massage Date of registration in PROSPERO 01 July 2021 Date of first submission 31 May 2021 Stage of review at time of this submission The review has not started

Yufan, Y. and H. Yingying (2022). "The impact of telemedicine on clinical outcomes for patients with cervical cancer: A systematic review and meta-analysis."
	Review question a. Does telemedicine improve clinical outcomes for cervical cancer patients? b. How much has telemedicine improved clinical outcomes for cervical cancer patients compared to other models of care? Searches PubMed, Scopus, Web of Science, PsycINFO, Cochrane and Embase. The search strategy will include the keywords listed in table1. The search terms will be adapted for use with other bibliographic databases. The language will be restricted to English or Chinese language articles, published prior to May 2022. The searches will be re-run prior to the final analyses and further studies will be included in the analyses. Types of study to be included We will include randomised trials to assess relevant outcome indicators and will complement this with observational studies (including cohort and case-control studies) to assess outcomes. Condition or domain being studied Telemedicine. Patients with cervical cancer. Participants/population a. Inclusion: Patients with cervical cancer; b. Exclusion: Under 18 years of age. Intervention(s), exposure(s) We focus on assessing how the use of telehealth modalities and other modalities (e.g. offline follow-up, etc.) can have a different impact on patients with cervical cancer. For example, the impact on patient disease progression, psychological outcomes. Comparator(s)/control Routine follow-up group (e.g. outpatient follow-up, etc.). Context Articles published in 2000 and later will be included in the analysis. Main outcome(s) Quality of life and psychological outcomes (e.g. anxiety, depression). Measures of effect Relative risks, odds ratios. Additional outcome(s) Not applicable. Data extraction (selection and coding) Title and abstracts of the studies will be scanned for inclusion criteria and those from additional sources will be screened by one author to identify those which met the inclusion and exclusion criteria outlined above. The full text of these will be reviewed and independently reviewed by one of the authors (YY). Another reviewer will also review the included studies. Two review authors will independently extract the data. Where there are disparities, consensus will be reached in a single meeting. Data from included studies were extracted, including patient demographics and effect size of outcome indicators. If these data were not available, or the methods required clarification, the authors were contacted. Articles were excluded from further analysis when the authors could not be contacted or the authors were unable to provide the information on request. Risk of bias (quality) assessment Two authors will independently assess the risk of bias. i. Blinding ii. Completeness of outcome data iii. Selective outcome reporting iv. Other sources of bias Disagreements between researchers will be resolved in a consensus meeting. The quality of cross-sectional studies was evaluated using The Cochrane Collaboration's tool for assessing risk of bias. Strategy for data synthesis A meta-analysis of the outcome indicators of the included studies was performed using STATA software. Any study for which RRs and ORs could be calculated was included in the meta-analysis. For each available variable, pooled dichotomous data were analyzed using random-effects meta-analysis and RRs, ORs. Heterogeneity was reported using the I^2 index, with larger scores indicating a greater proportion of heterogeneity. Significance was set at P＜0.05. Analysis of subgroups or subsets Clearly define what types of studies or individuals will be included in each group (e.g. study design, e.g. type of telemedicine, e.g. participant characteristics e.g. male/female, e.g. tumor stage). Contact details for further information Liping Zhang zlp80090@126.com Organisational affiliation of the review The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. http://www.wzhealth.com/ Review team members and their organisational affiliations Mr Yufan Yang. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Miss Yingying Huang. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Type and method of review Intervention, Meta-analysis, Systematic review Anticipated or actual start date 01 December 2021 Anticipated completion date 01 June 2022 Funding sources/sponsors None. Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Female; Humans; Telemedicine; Uterine Cervical Neoplasms Date of registration in PROSPERO 10 May 2022 Date of first submission 20 April 2022 Details of any existing review of the same topic by the same authors None.

Yukio, S., et al. (2023). "Levonorgestrel-releasing Intrauterine System Therapy Versus Oral Progestin Treatment for Endometrial Cancer: Systematic Review and Meta-analysis."
	Review question The aims are: 1. To determine the oncologic outcome of women who receive levonorgestrel-releasing Intrauterine System therapy or oral progestins treatment for fertility-preserving treatment for women with endometrial cancer. 2. To investigate the pregnancy outcomes of women who receive levonorgestrel-releasing Intrauterine System therapy or oral progestins treatment for fertility-preserving treatment for women with endometrial cancer. 3. To examine the adverse events of women who receive levonorgestrel-releasing Intrauterine System therapy or oral progestins treatment for fertility-preserving treatment for women with endometrial cancer. Searches Sources: PubMed (PubMed.gov), Embase (ELSEVIER), Cochrane Library (cochranelibrary.com), Scopus (ELSEVIER), Web of Science (Core Collection), and ClinicalTrials.gov Restrictions: Only studies published in English will be included Types of study to be included 1. Any study looking at conservative treatment outcome in patients with endometrial cancer with one or more treatment arm including at least one progestin therapy 2. Studies in any country 3. Eligible study designs were any type of study (randomized controlled trials, retrospective cohort studies, prospective cohort studies) 4. Eligible studies have to report at least primary outcome. Pregnancy rate, hysterectomy rate, recurrence rate, or adverse events are not necessarily requirement for the inclusion criteria. 5. Full text written in English is retained for the analysis Condition or domain being studied Although only 12% of incident cases of endometrial cancer in the U.S. occur in women younger than 50 years of age, the incidence of early-stage, low-grade endometrial cancer is increasing among women in their 30-years of age and recent trends toward delayed childbearing predict a growing population of premenopausal patients with endometrial cancer who may desire fertility preservation. A fertility-preserving treatment can be considered if the patients desire future childbearing and the cancer lesion does not invade myometrium. As an alternative to surgical management, progestin therapy is recommended for the conservative therapy. There are two representative types of therapy which are local therapy with hormone-releasing intrauterine device and systemic therapy with oral progestins. Participants/population The population being studied by this systematic review is women with a diagnosis of endometrial cancer and who undergo fertility-preserving treatment with levonorgestrel-releasing intrauterine system or oral progestins. Intervention(s), exposure(s) The standard treatment recommended for fertility preservation is hormonal therapy by progestins. Although the first choice has long been oral progestin therapy, levonorgestrel-releasing intrauterine system has been another option for the therapy. Comparator(s)/control Some studies we review may include a comparison of oral progestins and levonorgestrel-releasing intrauterine system. For the main outcome, we will not perform a comparative meta-analysis. On the other hand, for the secondary outcome, we compare oncologic and obstetric outcomes between patients who use levonorgestrel-releasing intrauterine system (intervention) and those who use oral progestins (control). Main outcome(s) The best complete response rate within 1 year among those who use levonorgestrel-releasing intrauterine system and those who use oral progestins. The combinations with Metformin/GnRH/Trans Cervical Resection are allowed. Additional outcome(s) 1. The best complete response rate within 1 year among those who use levonorgestrel-releasing intrauterine system only and those who use an oral progestin only. 2. Complete response rate at 6 months after the initiation of progestin therapy among those who use levonorgestrel-releasing intrauterine system and those who use oral progestins. 3. Pregnancy rate among those who use levonorgestrel-releasing intrauterine system and those who use oral progestins. The combinations with Metformin/GnRH/Trans Cervical Resection are allowed. 4. Comparative meta-analysis with RCTs and cohort studies with both levonorgestrel-releasing intrauterine system arm and oral progestins arm. 5. Hysterectomy rate, rate of progression to cancer, recurrence rate, and adverse events among those who use levonorgestrel-releasing intrauterine system and those who use oral progestins. The combinations with Metformin/GnRH/Trans Cervical Resection are allowed. Data extraction (selection and coding) Two authors will independently extract data from each study and four authors will review the extractions to arrive at a consensus. Data about study characteristics, outcomes, and any other relevant information will be extracted. Data extracted include: first author, year of publication, study design, treatment type (IUD vs. oral), number of patients in each study and each treatment arm, countries or regions the study held, complete response rate, timing of pathological assessment, pregnancy rate, hysterectomy rate, rate of progression to cancer, recurrence rate, and adverse events. Risk of bias (quality) assessment Risk of bias and quality of studies were assessed using the JBI appraisal tools for cohort studies and for randomized controlled trial. Two authors will independently assess each study and four authors will review the assessments to arrive at a consensus. Strategy for data synthesis Data synthesis will be presented both narratively and quantitatively via proportional meta-analysis and comparative meta-analysis. Data will be listed in the data extraction form, which will be an Excel sheet document. Studies will be analyzed using R software. The best complete response rate within 1 year among those who use levonorgestrel-releasing intrauterine system and those who use oral progestins will be evaluated by a percentage and 95% confidence interval. In both proportional and comparative meta-analysis, we will use forest plot, although the efficiency of treatments will be examined by Odds ratio in a comparative meta-analysis. Heterogeneity was determined by the I² statistic. The random-effects model will be used to calculate pooled effects. Analysis of subgroups or subsets Subgroup analyses of the combination of progestin drugs and the timing of the pathological assessment will be considered if data is sufficient or appropriate. The best complete response rate at any timing, pregnancy rate, hysterectomy rate, and recurrence rate were evaluated by a percentage and 95% confidence interval. In both proportional and comparative meta-analysis, we will use forest plot, although the efficiency of treatments will be examined by Odds ratio in a comparative meta-analysis. Heterogeneity was determined by the I² statistic. The random-effects model will be used to calculate pooled effects. Contact details for further information Yukio Suzuki yetii@yokohama-cu.ac.jp Organisational affiliation of the review Columbia University Medical Center Review team members and their organisational affiliations Dr Yukio Suzuki. Columbia University Medical Center Dr Jason D. Wright. Columbia University College of Physicians and Surgeons Jennifer S. Ferris. Columbia University Irving Medical Center Type and method of review Intervention, Meta-analysis, Systematic review Anticipated or actual start date 01 November 2023 Anticipated completion date 31 December 2023 Funding sources/sponsors None Conflicts of interest Language English Country United States of America Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms MeSH headings have not been applied to this record Date of registration in PROSPERO 17 November 2023 Date of first submission 07 November 2023

Yun, L., et al. (2019). "Acupuncture for infertile women without undergoing assisted reproductive techniques (ART): A systematic review and meta-analysis." Medicine 98(29): e16463.
	Background: Acupuncture is widely used for infertile women without undergoing assisted reproductive techniques (ART) in China but its effect is unclear. We aim to assess whether acupuncture and its combined therapy exert a positive influence on the outcome of female fertility.; Methods: We searched 6 databases, including Medline, EMBASE, the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure (CNKI), the China Science and Technology Journal Database (VIP), and Wan-Fang Data, from inception to June 2018. Studies of randomized controlled trials (RCTs) on women with infertility treated by acupuncture or its combined therapy were included. A meta-analysis was performed using Revman 5.3. The methodological quality of the studies was assessed through the risk of bias assessment tool by the Cochrane Collaboration.; Results: The pregnancy rate was significantly improved with treatment (RR = 1.84, 95% CI 1.62 to 2.10, P < .00001), compared to that in the control group. Subgroup analysis showed that comparing with pure western medicine intervention, no matter intervention with acupuncture alone, with acupuncture plus western medicine, with acupuncture plus Chinese medicine, or acupuncture plus Chinese medicine and western medicine, all of these subgroups exhibited significant improvement. The subgroup according to different types of infertility showed a significant improvement in infertility caused by polycystic ovary syndrome, tubal infertility, ovulatory disorder, and other factors. In addition, the ovulation rate and endometrial thickness were significantly increased. The level of LH was obviously decreased. Moreover, with acupuncture, less adverse effects occurred. The funnel plot revealed that publication bias might exist. All trials included had unclear risks in the aspects of allocation concealment, blinding of participants and personnel, blinding of outcome assessment, selective reporting, and other bias. Only 1 study was assessed as unclear risk in random sequence generation. In the incomplete outcome data, all studies were low risk, except 1.; Conclusions: Acupuncture and its combined therapy may be effective for treating female infertility. However, the included studies are not robust enough to draw a firm conclusion due to the not robustly sampled quality of the included studies. Future high-quality RCTs are needed to confirm our findings.

Yun, Z., et al. (2024). "A meta-analysis examining the impact of open surgical therapy versus minimally invasive surgery on wound infection in females with cervical cancer." International wound journal.
	A meta-analysis study was executed to measure the effect of minimally invasive surgery (MIS) and open surgical management (OSM) on wound infection (WI) in female's cervical cancer (CC). A comprehensive literature study till February 2023 was applied and 1675 interrelated investigations were reviewed. The 41 chosen investigations enclosed 10 204 females with CC and were in the chosen investigations' starting point, 4294 of them were utilizing MIS, and 5910 were utilizing OSM. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilized to compute the value of the effect of MIS and OSM on WI in female's CC and by the dichotomous approaches and a fixed or random model. The MIS had significantly lower WI (OR, 0.23; 95% CI, 0.15-0.35, p < 0.001) with no heterogeneity (I 2 = 0%) and postoperative aggregate complications (PACs) (OR, 0.49; 95% CI, 0.37-0.64, p < 0.001) in females with CC and compared OSM. However, MIS compared with OSM in females with CC and had no significant difference in pelvic infection and abscess (PIA) (OR, 0.59; 95% CI, 0.31-1.16, p = 0.13). The MIS had significantly lower WI, and PACs, though, had no significant difference in PIA in females with CC and compared with OSM. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis. (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Yunan, H., et al. (2022). "Comparative efficacy and safety of 36 intervention strategies for pregnancy outcomes with Recurrent implantation failures: a systematic review and network meta-analysis."
	
YunZi, W., et al. (2023). "Clinical benefit analysis of PD-1/PD-L1 inhibitors in patients with metastatic and refractory cervical cancer: a meta-analysis and systematic review."
	Review question How does the clinical benefit of PD-1/PD-L1 inhibitors compare to other anti-tumor drugs in patients with metastatic and refractory cervical cancer? Searches Sources that will be searched for the systematic review on the clinical benefit of PD-1/PD-L1 inhibitors compared to other anti-tumor drugs in patients with metastatic and refractory cervical cancer may include the following: 1. Bibliographic databases such as MEDLINE, EMBASE, and Cochrane. 2. Reference lists of eligible studies and review articles. 3. Key journals in the field of oncology and gynecology. 4. Conference proceedings related to cervical cancer research. 5. Trials registers for ongoing or completed clinical trials. 6. Internet resources that provide relevant information. 7. Contact with study investigators, experts, and manufacturers for additional insights. The search will cover a specific time period, usually from the inception of the databases to September 2023, depending on the availability of relevant studies. The search will be restricted to studies published in the English language. It is considered good practice to re-run the searches just before the final analysis to identify any newly published studies. Additionally, efforts will be made to seek unpublished studies to ensure comprehensive coverage of the topic. Types of study to be included We will include all randomized, cohort and observational studies to assess the beneficial effects, and if studies report adverse events, we will also assess the harms. Condition or domain being studied Cervical cancer. Objective response rate (ORR), one-year overall survival (OS) rate, one-year progression-free survival (PFS) rate, and hazard ratios (HRs) for OS or PFS in patients. Participants/population Inclusion: (1) Patients had persistent, recurrent, or etastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix; (2)Patients who had received at least one line of systemic therapy or could not tolerate chemotherapy were eligible.;(3)Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;(4)have at least 1 measurable target lesion according to the solid tumor response evaluation criteria (RECIST version 1.1). Exclusion: (1) Adolescents (under 18 years of age); (2) Patients with prior immune checkpoint inhibitor therapy;(3)had other malignant tumors;(4) had incomplete data; and/or;(5) had severe comorbidities, including severe heart, lung, renal, or coagulation disorders. Intervention(s), exposure(s) Interventions: PD-1/PD-L1 inhibitors monotherapy or in combination with other anticancer drugs.

Yuping, S., et al. (2022). "Efficacy of probiotics in the treatment of adult female bacterial vaginosis: A meta-analysis."
	Review question The aim of this meta-analysis of randomized controlled trials is to evaluate the efficacy of probiotics in the treatment of adult female bacterial vaginosis. Searches We searched articles in three electronic database including PubMed, EMBASE and Cochrane Library. All the English publications were searched without any restriction of countries or time. Reference lists of all selected articles were independently screened to identify additional studies left out in the initial search. Types of study to be included Randomized controlled trials (RCTs) will be included. Condition or domain being studied Bacterial vaginosis has a high incidence in adult women and is one of the most common gynecological diseases in clinic. It not only increases the risk of diseases such as pelvic inflammation and venereal diseases, but also leads to an increased risk of adverse pregnancy outcomes. In addition, bacterial vaginosis is easy to relapse after conventional antibiotic treatment, which seriously affects the quality of life of patients. Participants/population Inclusion: adult females (over 18 years of age) with bacterial vaginosis (BV) (as diagnosed using any recognized diagnostic criteria). Exclusion: adult females who were diagnosed as HIV positive or urogenital infections of another type or pregnant or breastfeeding. Intervention(s), exposure(s) Metronidazole plus probiotics. Comparator(s)/control Metronidazole plus placebo. Main outcome(s) positive Nugent score (7-10) after 1month intervention. Measures of effect RR Additional outcome(s) positive signs and symtoms Measures of effect RR Data extraction (selection and coding) Two authors will independently extract data. Any disagreement will be resolved by discussion until consensus is reached or by consulting a third author. The following data will be extracted: author, year of publication, original inclusion criteria, total number of people included in the study the rest of the final follow-up. Risk of bias (quality) assessment Two reviewers will independently assess risk of bias based on the following domains from recommendations from the Cochrane handbook: 1. Adequate sequence generation; 2. Allocation concealment; 3. Blinding; 4. Incomplete outcome data and how it was addressed; 5. Selective reporting of the outcome; 6. Any other biases. results of bias assessment will be presented in a figure and a graph indicating low, high or unclear risk of bias for each of the 6 items in each trial. Sensitivity analysis will be conducted based on the bias assessment to assess robustness of results. Strategy for data synthesis Relative Risk (RR) and its 95% confidence intervals (95% CI) will be calculated for the bacterial vaginosis in each included trial based on intention to treat (ITT). Due to expected heterogeneity among the trials, Meta-analysis using the random-effects model will be conducted to pool RR. Analysis of subgroups or subsets Sensitivity analysis to assess robustness of results and subgroup analysis to determine whether the summary effects vary in relation to clinical characteristics of the trials included are pre-specified. For sensitivity analysis the treatment effects will be examined based on bacterial vaginosis or not as an outcome was assessed a priori or post hoc. If this was not clear, the assumption that it was considered post hoc was made. In addition, sensitivity analysis, including only those trials free of any assessed bias will be conducted.Two subgroup analyses will also be undertaken: The first to assess if the different drug groups produce different treatment effects; The second to investigate the effect of different medication time on the outcome. Contact details for further information Yuping Shan 1835603915@qq.com Organisational affiliation of the review Qingdao University https://www.qdu.edu.cn/ Review team members and their organisational affiliations Miss Yuping Shan. Qingdao University Mr Guangning Wang. Qingdao University Mr Zicheng Cui. Qingdao University Mrs Aiping Chen. The Affiliated Hospital of Qingdao University Type and method of review Systematic review Anticipated or actual start date 02 January 2022 Anticipated completion date 01 May 2022 Funding sources/sponsors None Grant number(s) State the funder, grant or award number and the date of award None Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Adult; Anti-Bacterial Agents; Female; Humans; Probiotics; Vaginosis, Bacterial Date of registration in PROSPERO 14 March 2022 Date of first submission 11 February 2022

Yusnita, Y., et al. (2021). "Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis."
	Review question How does elagolix treatment improve symptoms severity and quality of life in women with heavy menstrual bleeding associated with uterine fibroid? How does elagolix treatment impact on uterine volume and fibroid volume? Does elagolix treatment have better profile of adverse event and reduce hypoestrogenic effect? Searches [1 change] We searched the Cochrane Central Register of Controlled Trials CENTRAL (latest Issue), PubMed, ScienceDirect, Scopus, EBSCOhost and MEDLINE (2017 to present). We used the search strategy in Appendix 1 to search MEDLINE and CENTRAL. We adapted the search strategy for other databases. We restricted the publications to English language only. We checked the reference list of identified RCTs and review articles to find unpublished trials or trials not identified by electronic searches. We also contacted experts in the field and pharmaceutical companies which market elagolix to identify unpublished trials. We searched for ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) http://www.who.int/ictrp/en/ and www.ClinicalTrials.gov. We scanned the titles and abstracts from the searches and obtained full-text articles when they appear to meet the eligibility criteria, or when there was insufficient information to assess the eligibility. We assessed the eligibility of the trials independently and documented the reasons for exclusion. We resolved any disagreements between the review authors by discussion. We contacted the authors if clarification is needed. We translated papers in languages other than English. Search strategy CENTRAL, PubMed, ScienceDirect, Scopus, EBSCOhost 1 leiomyoma 2 fibroid 3 #1 OR #2 4 menorrhagia 5 #3 AND #4 6 ELAGOLIX 7 #5 AND #6 8 "menorrhagia"[MeSH Terms] OR "menorrhagia"[All Fields] OR "menorrhagias"[All Fields] OR ("menorrhagia"[MeSH Terms] OR "menorrhagia"[All Fields] OR ("heavy"[All Fields] AND "menstrual"[All Fields] AND "bleeding"[All Fields]) OR "heavy menstrual bleeding"[All Fields]) 9 "elagolix"[Supplementary Concept] OR "elagolix"[All Fields] 10 ((menorrhagia) OR (heavy menstrual bleeding) AND ((ffrft[Filter]) AND (fha[Filter]) AND (randomizedcontrolledtrial[Filter]) AND (fft[Filter]))) AND (elagolix AND ((ffrft[Filter]) AND (fha[Filter]) AND (randomizedcontrolledtrial[Filter]) AND (fft[Filter]))) 11 ("menorrhagia"[MeSH Terms] OR "menorrhagia"[All Fields] OR "menorrhagias"[All Fields] OR ("menorrhagia"[MeSH Terms] OR "menorrhagia"[All Fields] OR ("heavy"[All Fields] AND "menstrual"[All Fields] AND "bleeding"[All Fields]) OR "heavy menstrual bleeding"[All Fields])) AND ("loattrfree full text"[Filter] AND "hasabstract"[All Fields] AND "randomized controlled trial"[Publication Type] AND "loattrfull text"[Filter]) AND (("elagolix"[Supplementary Concept] OR "elagolix"[All Fields]) AND ("loattrfree full text"[Filter] AND "hasabstract"[All Fields] AND "randomized controlled trial"[Publication Type] AND "loattrfull text"[Filter])) Types of study to be included 1. Archer DF, Stewart EA, Jain RI, Feldman RA, Lukes AS, North JD, et al. Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study. Fertility and Sterility. 2017;108(1):152-60.e4. 2. Carr BR, Stewart EA, Archer DF, Al-Hendy A, Bradley L, Watts NB, et al. Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial. Obstetrics and gynecology. 2018;132(5):1252-64. 3. Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, et al. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids. The New England journal of medicine. 2020;382(4):328-40. 4. Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, et al. Elagolix Treatment for Up to 12 Months in Women with Heavy Menstrual Bleeding and Uterine Leiomyomas. Obstetrics and gynecology. 2020;135(6):1313‐26. Condition or domain being studied Uterine fibroids are benign and noncancerous tumor arising from fibroblasts of the myometrium. Most women are symptomatic. If symptomatic, they may present with abnormal bleeding, pelvic pain and dyspareunia (Stewart, 2001). Most cases of uterine fibroids are being diagnosed from incidental ultrasound finding. Uterine leiomyomas may also compromise reproductive functions, subfertility and have adverse pregnancy outcome (Neri, 2019). Symptomatic uterine fibroids negatively impact physical and social activities, quality of life, economic burden and work productivity (Erica, 2018). It has been estimated that the prevalence of uterine fibroid based on clinical assessment was at 33%, ultrasound scan at 50% and histological examination of hysterectomy specimens at 77% (Cramer and Patel, 1990). Most common risk factors of uterine fibroids are including family history, ethnicity, obesity, marital status, pregnancy interval, ovarian steroid exposure, nulliparous and vitamin D deficiency. Treatments can be nonhormonal, hormonal pharmacological compounds, and surgical treatment. Surgery is an option when women are symptomatic (ElKafas, 2018). Modalities treatment varies and individualized based on symptoms severity, age, size, location and fertility desirable. Medical therapies include GnRH agonist, COCPs, tibolone, selective estrogen receptor modulator, ulipristal, danazol and levonogestrel LNG-IUS Mirena. The surgical options include myomectomy, hysterectomy, endometrial uterine artery embolization and endometrial ablation (Nowak, 1999). Participants/population [1 change] We included premenopausal women aged 18 to 51 years at the time of screening with heavy menstrual bleeding demonstrated by >80 mL of menstrual blood loss per menstrual cycle. Intervention(s), exposure(s) Gonadotropin-releasing hormone antagonist is a synthetic peptide that is structurally analogous to the natural GnRH hormones act by binding to GnRH receptors in the pituitary gland and blocking the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Elagolix is a second-generation GnRH antagonist. It is a potent, non-peptide GnRH-antagonist immediately stop GnRH receptors causing the suppression of gonadotropin and eventually reducing estrogen and progesterone production from the ovaries (Barra, 2020). GnRH antagonist have an immediate and rapidly reduce sex hormone level without initial surge like GnRH agonist. The growth or abnormal proliferation of uterine leiomyoma is restricted due to lack of exposure of estrogen. Hence, the volume of menstrual bleeding together with uterine and fibroid volume are also decreasing. Additional oestradiol/norethindrone acetate in the treatment regime can reduce the hypoestrogenic effect (Nader, 2020). Varying dosage of elagolix evaluated and reviewed to determine its effectiveness. The suppression in steroid hormone level result in significant reduction menstrual blood loss, achieving amenorrhea and improving hemoglobin level and fibroid shrinkage (Nowak, 1999). Elagolix has better profile of adverse events and concomitant with add-back therapy can prevent bone loss due to hypoestrogenic effect and improve safety during elagolix treatment. Comparator(s)/control Placebo or elagolix with estradiol/norethindrone acetate either standard dose or low dose. Context The study conducted in 86 sites in the United States, Puerto Rico, Canada, Chile, and the United Kingdom. Premenopausal women who were between the ages of 18 and 51 years at the time of screening and who had an ultrasonography-confirmed diagnosis of uterine fibroids and heavy menstrual bleeding, as defined by more than 80 ml of menstrual blood loss per menstrual cycle for at least two separate cycles were recruited in this study at clinic. Main outcome(s) [1 change] 1. Reduction of menstrual blood loss <80 ml 2. Reduction of >50% menstrual blood loss Reduction of menstrual blood loss (MBL) <80 ml and >50% from baseline to final month was measured by the alkaline hematin method, which objectively quantified the amount of blood in sanitary products collected. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period. Participants with no post-baseline MBL data were assigned an MBL value of zero Measures of effect We measured the treatment effect for dichotomous outcomes using risk ratios (RRs) and absolute risk reduction, and for continuous outcomes we used mean differences (MDs); both with 95% confidence intervals (CIs). Additional outcome(s) [1 change] 1. Reduction in uterine volume 2. Reduction in fibroid volume Reduction of uterine volume and fibroids volume were measured either by transabdominal ultrasound or transvaginal ultrasound. 3. Symptoms severity 4. Health-related quality of life The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consciousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0-to-100-point scale to provide a total score for each of the 2 components. Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life. 5. Haemoglobin level Any improvement of hemoglobin level was measured with blood specimen. 6. Bone mineral density Loss of bone mineral density was assessed by dual-energy x-ray absorptiometry scans of the lumbar spine, total hip and femoral neck 7. Adverse event or side effect medication Measures of effect We measured the treatment effect for dichotomous outcomes using risk ratios (RRs) and absolute risk reduction, and for continuous outcomes we used mean differences (MDs); both with 95% confidence intervals (CIs). Data extraction (selection and coding) [1 change] Using data extraction form, from each of the selected trials we extracted: • study setting; • participant characteristics (age, sex, ethnicity); • methodology (number of participants randomized and analyzed, duration of follow-up); • dosage of elagolix • dosage of add back therapy • reduction of monthly menstrual blood loss <80 ml • reduction of >50% menstrual blood loss • reduction in uterine volume • reduction in fibroid volume • symptoms severity • health-related quality of life • haemoglobin level • bone mineral density • adverse event or side effect medication Risk of bias (quality) assessment [1 change] We assessed the risk of bias based on random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, completeness of outcome data, the selectivity of outcome reporting and other bias (Higgins 2019). We resolved any disagreements by discussion. We assessed the quality of evidence for primary and secondary outcomes according to GRADE methodology (Guyatt 2008) for risk of bias, inconsistency, indirectness, imprecision, and publication bias; classified as very low, low, moderate, or high. Strategy for data synthesis [1 change] We planned to undertake meta-analyses using Review Manager 5.4 software (RevMan 2020) and used random-effects model to pool data. Thresholds for the interpretation of the I² statistic can be misleading, since the importance of inconsistency depends on several factors. We planned to use the guide to interpretation of heterogeneity as outlined: 0% to 40% might not be important; 30% to 60% may represent moderate heterogeneity; 50% to 90% may represent substantial heterogeneity; and 75% to 100% would be considerable heterogeneity (Higgins 2019). We assessed the presence of heterogeneity in two steps. First, we assessed obvious heterogeneity at face value by comparing populations, settings, interventions and outcomes. Second, we assessed statistical heterogeneity by means of the I² statistic (Higgins 2019). Analysis of subgroups or subsets [1 change] The planned subgroup analyses were: 1. Dosage of elagolix 2. Dosage of estradiol/norethindrone acetate. We were unable to carry out subgroup dosage of elagolix as outlined in the protocol because there were insufficient trials. However, we conducted subgroup analyses on: 1. Frequency of drug administration either twice daily (bd) or once daily (qd) administration. 2. Uterine volume. 4. Fibroid volume Contact details for further information Dr Yusnita Yusof yusofyusnita3786@gmail.com Organisational affiliation of the review University Sains Malaysia Review team members and their organisational affiliations Dr Yusnita Yusof. University Sains Malaysia Assistant/Associate Professor Noorhayati Mohd Noor. Department of Family Medicine, Universiti Sains Malaysia Dr Juliawati Muhamad. Department of Family Medicine, Universiti Sains Malaysia Dr Imran Ahmad. Department of Family Medicine, Universiti Sains Malaysia Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 01 February 2021 Anticipated completion date 30 April 2021 Funding sources/sponsors [1 change] None Conflicts of interest Language English Country Malaysia Published protocol https://www.crd.york.ac.uk/PROSPEROFILES/233898_PROTOCOL_20220806.pdf

Yu-Yun, H., et al. (2023). "Effects of Exercise on Secondary Lower Limb Lymphedema in Gynecologic Cancer: A Systematic Review and Meta-Analysis."
	Review question The PICO (Population/Intervention/Comparison/Outcome) question is whether exercise (I) can alleviate lower limb lymphedema (O) for patients with gynecological cancer after surgery (P). Searches To find articles related to exercise, gynecologic cancer, and lower limb lymphedema, we will electronically search the CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Library (including CENTRAL), Embase, MEDLINE, Scopus, and Web of Science. We seek a consultant from a health sciences librarian with expertise in systematic review. The most recent search took place in May 2023. Types of study to be included Randomized control trials or quasi-experimental designs Condition or domain being studied Effects of Exercise on Lower Limb Lymphedema in Gynecologic Cancer Participants/population Patients aged 20-80 with gynecological cancer after surgery Intervention(s), exposure(s) Exercise Comparator(s)/control Standard care or health education Context We will contain studies conducted in a home-based or facility setting. Main outcome(s) Limb volume Additional outcome(s) Pain and heaviness

Yuzhuo, Z. and K. Xianglu (2022). "Effects of Auricular Acupressure on Dysmenorrhoea: a system review and meta-analysis of randomized controlled trials."
	Review question Auricular acupressure is widely used in treatment of dysmenorrhoea, but the safety and efficacy of auricular acupressure on dysmenorrhoea are still lack of evidence-based basis. Searches [1 change] PubMed, CINAHL, EMBASE, Wangfang database, CQVIP Database, and China National Knowledge Infrastructure (CNKI) database will be searched until June 10, 2022. A keyword such as “Auricular Acupressure”, “dysmenorrhoea”, “randomized”, “randomized controlled trial”, etc. will be used to search without restrictions on language Types of study to be included Randomized controlled trials Condition or domain being studied Dysmenorrhea is defined as a complex of symptoms with cramping pain in the lower abdomen, which occurs during menstruation or before it. Auricular acupressure is a long-standing treatment in Traditional Chinese Medicine technique and may be a valuable treatment in improving menstrual symptoms. We aimed to investigate the effects of auricular acupressure for the management of primary dysmenorrhea by using meta-analysis. Participants/population People suffering from dysmenorrhea. Intervention(s), exposure(s) Auricular acupressure. Comparator(s)/control Auricular acupressure versus basic or conventional treatment; Auricular acupressure combined with basic or conventional treatment versus basic or conventional treatment used alone; Auricular acupressure versus other treatment; Auricular acupressure versus placebo or sham acupressure. Main outcome(s) [1 change] Cure rate, total effective rate，Pain (VAS)， Additional outcome(s) [1 change] Short-form Menstrual Distress Questionnaire (MDQs), symptom scores, NO， Data extraction (selection and coding) The relevant information will be extracted from the included articles, including countries, publication year, age and gender of patients, disease, type of surgery, study design, blind method, intervention type, acupoints, duration of intervention, sample size, outcomes, safety, and advent events. Any disagreements for literature screening and data extraction will be resolved by discussion, or consultation with a third investigator until final consensus is reached. Risk of bias (quality) assessment The quality of the included RCTs will be independently assessed by two reviewers according to the Cochrane Collaboration recommendations. The literature will be estimated from seven aspects: sequence generation, allocation concealment, blind of participants and personnel, blind of outcome, incomplete outcome data, selective reporting and other biases. The risk of bias will be judged on three levels: high, unclear and low. A primary reviewer will be consulted to resolve any discrepancies. Strategy for data synthesis The meta-analysis of the included studies will be done by using the review manger 5.3 software, and illustrated by the forest map intuitively. Uncertainty will be expressed with 95% confidence intervals (95% CI). Standard mean differences (SMDs) or mean differences (MDs) will be used to analyze continuous outcomes. Dichotomous data will be described as odds ratios (OR) associated with 95% CI. Analysis of subgroups or subsets Heterogeneity will be assessed by using Cochran Q-test and I² index18. P＜0.10 (Cochran Q-test) and I² statistic less than 50% indicate an acceptable heterogeneous so that a random effects models will be employed; otherwise, a fixed effects models will be selected for the meta-analysis, and we will explore the reasons for substantially heterogeneous including conducting sensitivity analysis and subgroup analysis. Subgroup analysis will be performed according to intervention parameters. P-values＜0.05 is considered to be a statistically significant. Contact details for further information Yuzhuo Zhang zhangmomo1117@163.com Organisational affiliation of the review Guangzhou University of Chinese Medicine Review team members and their organisational affiliations Dr Yuzhuo Zhang. Guangzhou University of Chinese Medicine Xianglu Kong. Jiande hospital of integrated traditional Chinese and Western Medicine Type and method of review Meta-analysis, Systematic review Anticipated or actual start date 10 June 2022 Anticipated completion date 31 August 2022 Funding sources/sponsors None Conflicts of interest Language English Country China Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD Subject index terms Acupressure; Dysmenorrhea; Female; Humans; Pain Measurement; Randomized Controlled Trials as Topic Date of registration in PROSPERO 19 June 2022 Date of first submission 08 June 2022 Stage of review at time of this submission The review has not started

Zaat, T. R., et al. (2021). "Increased obstetric and neonatal risks in artificial cycles for frozen embryo transfers?" Reproductive Biomedicine Online 42(5): 919‐929.
	Research question: What are the obstetric and neonatal risks for women conceiving via frozen–thawed embryo transfer (FET) during a modified natural cycle compared with an artificial cycle method. Design: A follow‐up study to the ANTARCTICA randomized controlled trial (RCT) (NTR 1586) conducted in the Netherlands, which showed that modified natural cycle FET (NC‐FET) was non‐inferior to artificial cycle FET (AC‐FET) in terms of live birth rates. The current study collected data on obstetric and neonatal outcomes of 98 women who had a singleton live birth. The main outcome was birthweight; additional outcomes included hypertensive disorder of pregnancy, premature birth, gestational diabetes, obstetric haemorrhage and neonatal outcomes including Apgar scores and admission to the neonatal ward or the neonatal intensive care unit and congenital anomalies. Results: Data from 82 out of 98 women were analysed according to the per protocol principle. There was no significant difference in the birthweights of children born between groups (mean difference –124 g [–363 g to 114 g]; P = 0.30). Women who conceived by modified NC‐FET have a decreased risk of hypertensive disorders of pregnancy compared with AC‐FET (relative risk 0.27; 95% CI 0.08–0.94; P = 0.031). Other outcomes, such as rates of premature birth, gestational diabetes or obstetric haemorrhage and neonatal outcomes, were not significantly different. Conclusions: The interpretation is that modified NC‐FET is the preferred treatment in women with ovulatory cycles undergoing FET when the increased risk of obstetrical complications and potential neonatal complications in AC‐FET are considered.

Zaat, T. R., et al. (2021). "Is home-based monitoring of ovulation to time frozen embryo transfer a cost-effective alternative for hospital-based monitoring of ovulation? Study protocol of the multicentre, non-inferiority Antarctica-2 randomised controlled trial." Human Reproduction Open 2021(4): hoab035.
	Study Question: The objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the NC. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born).; What Is Known Already: FET is at the heart of modern IVF. To allow implantation of the thawed embryo, the endometrium must be prepared either by exogenous oestrogen and progesterone supplementation (artificial cycle (AC)-FET) or by using the NC to produce endogenous oestradiol before and progesterone after ovulation to time the transfer of the thawed embryo (NC-FET). During an NC-FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified (m)NC-FET or hospital-based monitoring). From the woman's point of view, a more natural approach using home-based monitoring of the ovulation with LH urine tests to allow a natural ovulation to time FET may be desired (true NC-FET or home-based monitoring).; Study Design Size Duration: This is a multicentre, non-inferiority prospective randomised controlled trial design. Consenting women will undergo one FET cycle using either true NC-FET or mNC-FET based on randomisation.; Participants/materials Setting Methods: Based on our sample size calculation, the study group will consist of 1464 women between 18 and 45 years old who are scheduled for FET. Women with anovulatory cycles, women who need ovulation induction and women with a contra indication for pregnancy will be excluded. The primary outcome is ongoing pregnancy. Secondary outcomes are cancellation rates of FET, pregnancy outcomes (including miscarriage rate, clinical pregnancy, multiple pregnancy rate and live birth rate). Costs will be estimated by counting resource use and calculating unit prices.; Study Funding/competing Interests: The study received a grant from the Dutch Organisation for Health Research and Development (ZonMw 843002807; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis, and interpretation of data or writing of the manuscript. F.B. reports personal fees from member of the external advisory board for Merck Serono, grants from Research support grant Merck Serono, outside the submitted work. A.E.P.C. reports and Unrestricted grant of Ferring B.V. to the Center for Reproductive medicine, no personal fee. Author up-to-date on Hyperthecosis. Congress meetings 2019 with Ferring B.V. and Theramex B.V. M.G. reports Department research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the submitted work. E.R.G. reports personal fees from Titus Health Care, outside the submitted work. C.B.L. reports grants from Ferring, grants from Merck, from Guerbet, outside the submitted work. The other authors have none to declare.; Trial Registration Number: Dutch Trial Register (Trial NL6414 (NTR6590), https://www.trialregister.nl/).; Trial Registration Date: 23 July 2017.; Date of First Patient’s Enrolment: 10 April 2018. (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Zacharakis, D., et al. (2023). "Enhanced Recovery Protocols in Urogynecologic and Pelvic Floor Reconstructive Surgery: A Systematic Review and Meta-Analysis." Urogynecology (Philadelphia, Pa.) 29(1): 21-32.
	Importance: The implementation of Enhanced Recovery After Surgery (ERAS) protocols may optimize the clinical outcome of surgical patients, by reducing the length of hospital stay (LOS) and improving the quality of recovery.; Objective: This study aims to evaluate the impact of ERAS protocols in the intraoperative and postoperative course of patients undergoing pelvic floor reconstructive surgery.; Methods: A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library was conducted up to January 2022, using the Systematic Reviews and Meta-analyses guidelines. Search terms, such as ERAS, urogynecology, sacrocolpopexy were tailored to each database as necessary. Statistical analysis was performed using the RevMan 5.4 software. Confidence intervals (CI) were set at 95%. Mean difference and risk ratio were used in the analysis, and the results were calculated using the random effect model.; Results: Six studies that reported outcomes of 1,153 women were included. The ERAS protocols were implemented in 553 women, whereas the remaining 600 received standard perioperative care. A significantly shorter LOS (mean difference, -16.17 hours; 95% CI, -24.07 to -8.26 hours; P < 0.0001) and a higher proportion of patients discharged within 24 hours postoperatively was observed in ERAS patients compared with non-ERAS controls (risk ratio, 3.08; 95% CI, 2.00-4.75; P < 0.00001). Operative time, estimated blood loss, complications, and readmission rates did not differ between the 2 groups.; Conclusions: Our analysis showed that ERAS protocols have a favorable impact on the perioperative course of urogynecologic populations. More research is required to determine those key components of ERAS protocols, specifically applicable and more beneficial to women with pelvic floor disorders.; Competing Interests: The authors have declared that they have no conflicts of interest. (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Zacharakis, D., et al. (2022). "Preemptive Infiltration of Local Anesthetics During Vaginal Hysterectomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials." Urogynecology 28(10): 667-678.
	IMPORTANCE: Vaginal hysterectomy (VH) is the preferred route of choice for women desiring hysterectomy to treat uterine pathology, including premalignant conditions and fibroids. OBJECTIVE: The aim of this study was to evaluate the impact of the use of preemptive local analgesia (LA) on postoperative pain and perioperative outcomes for women undergoing VH. STUDY DESIGN: A systematic search of 4 electronic databases (MEDLINE, Scopus, Cochrane CENTRAL Register of Controlled Trials, and Clinicaltrials.gov) was performed for articles published up to January 2021. All randomized controlled trials that presented outcomes of patients who underwent VH due to pelvic floor disorders or other benign gynecological disorders and received local infiltration analgesia were finally included. RESULTS: A total of 5 studies with 277 women (138 LA group vs 199 no-LA group) who underwent a VH were included in the present meta-analysis. Mean pain scores at both 30 minutes to 2 hours and 3 to 6 hours postoperatively were significantly lower in the LA group compared with the non-LA group (220 patients: mean difference [MD], -1.75; 95% confidence interval [CI], -2.77 to -0.74; P = 0.0007; and 220 patients: MD, -1.68; 95% CI, -2.28 to 1.09; P < 0.00001, respectively). Morphine/narcotic opioid-based consumption up to 24 hours postoperatively was significantly reduced in the LA group compared with the non-LA group (197 patients MD, -9.47 mg; 95% CI, -16.51 to -2.43; P = 0.008). CONCLUSIONS: The use of preemptive LA during VH seems to be beneficial especially with regard to short-term postoperative pain and opioid use. However, further studies are needed to identify the optimal anesthetic regimen, the dosage, and sites of application aiming to achieve the optimal benefit in the postoperative management.

Zacharakis, D., et al. (2021). "Pelvic floor reconstructive surgery under local anesthesia: A systematic review and meta-analysis." Neurourology and Urodynamics 40(6): 1304-1332.
	Aims: The decision on the appropriate type of anesthesia for pelvic floor repair depends on a variety of factors including patients' age, performance status, comorbidities, cost-effectiveness and personal preferences. We aim to review the literature on urogynecological procedures performed under local anesthesia (LA).; Methods: A systematic search of four electronic databases was conducted for articles published up to May 2020. Studies reporting outcomes of women who underwent pelvic floor reconstructive surgery under LA with or without sedation, were considered eligible.; Results: Nineteen studies (14 noncomparative and 5 comparative), including 1626 cases of urogynecological procedures under LA were recruited. Meta-analysis revealed significantly lower mean pain scores in LA group compared to general-regional anesthesia one (GA/RA) at both 4-6 h and 8-18 h postoperatively (160 patients; mean difference [MD], -1.70; 95% confidence interval [CI]: -3.12, -0.28; p = 0.02 and 160 patients; MD, -0.72; 95% CI: -1.17, 0.27; p = 0.002, respectively). Pain scores at >24 h did not differ among the two groups (160 patients; MD, -0.28; 95% CI: -0.60-0.05; p = 0.10). Intra- and postoperatively morphine use was not different among patients who received LA and GA during prolapse surgery while nausea rates were significantly lower in LA group compared to RA group 8 h postoperatively.; Conclusions: LA with or without sedation represents a safe and efficient alternative anesthetic technique for urogynecological procedures with improved pain scores in up to 18 h postoperatively especially in patients who underwent surgery for SUI. LA is feasible and could be offered to patients undergoing pelvic floor surgery allowing a prompt postoperative recovery. (© 2021 Wiley Periodicals LLC.)

Zachou, G., et al. (2023). "Evaluation of follow-up strategies for women with epithelial ovarian cancer following completion of primary treatment." The Cochrane Database of Systematic Reviews 8: CD006119.
	Background: This is an update of a previous Cochrane Review, last updated in 2014. Ovarian cancer is the eighth most common cancer and seventh most common cause of death due to cancer in women worldwide. Traditionally, most women who have been treated for cancer undergo long-term follow-up in secondary care. However, it has been suggested that the use of routine review may not be effective in improving survival, or health-related quality of life (HRQOL), or relieving anxiety. In addition, traditional follow-up may not be cost-effective.; Objectives: To compare the potential effects of different strategies of follow-up in women with epithelial ovarian cancer, following completion of primary treatment.; Search Methods: For this update, we searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL 2022, Issue 11, MEDLINE, and Embase from August 2013 to November 2022. We also searched review articles and contacted experts in the field.; Selection Criteria: All randomised controlled trials (RCTs) that evaluated follow-up strategies for women with epithelial ovarian cancer following completion of primary treatment.; Data Collection and Analysis: We followed standard Cochrane methodology. Two review authors independently selected potentially relevant trials, extracted data, and assessed risk of bias. They compared results, and resolved disagreements by discussion. We assessed the certainty of evidence, using the GRADE approach, for the outcomes of interest: overall survival (OS), health-related quality of life (HRQOL), psychological effects, and cost analysis.; Main Results: For this update, we included one new RCT, including 112 women with ovarian, fallopian tube, or peritoneal cancer, who had completed primary treatment by surgery, with or without chemotherapy. This study reported the effect of individualised, i.e. individually tailored, nurse-led follow-up versus conventional medical follow-up on HRQOL, psychological outcomes, and cost-analysis. Individualised follow-up improved HRQOL in one of the two scales, with a decrease in mean difference (MD) in the QLQ-C30 discomfort scale following 12 months of individualised treatment compared to 12 months of conventional treatment (MD -5.76 points, 95% confidence interval (CI) -10.92 to -0.60; 1 study, 112 participants; low-certainty evidence; minimal important difference 4 to 10 points). There may be little or no difference in the other HRQOL scale (QLQ-Ov28, MD -0.97 points, 95% CI -2.57 to 0.63; 1 study, 112 participants: low-certainty evidence); psychological outcome, measured with the hospital anxiety and depression scale (HADS; MD 0.10 point, 95% CI -0.81 to 1.02; 1 study, 112 participants: low-certainty evidence), or cost analysis (MD -GBP 695.00, 95% CI -1467.23 to 77.23; 1 study, 112 participants: moderate-certainty evidence). Our previous review included one RCT, with 529 women in a confirmed remission, with normal CA125 concentration and no radiological evidence of disease, after surgery and first-line chemotherapy for ovarian cancer. This study evaluated immediate treatment of ovarian cancer relapse following a rise of serum CA125 levels versus delaying treatment until symptoms developed for OS, and HRQOL. There was little or no difference in OS between the immediate and delayed arms after a median follow-up of 56.9 months (unadjusted hazard ratio (HR) 0.98, 95% CI 0.80 to 1.20; 1 study, 529 participants; moderate-certainty evidence). Time from randomisation to first deterioration in global health score or death was shorter in the immediate treatment group than in the delayed treatment group (HR 0.71, 95% CI 0.58 to 0.88).; Authors' Conclusions: Limited evidence from one trial suggests that routine surveillance with CA125 in asymptomatic women and treatment at CA125-defined relapse does not seem to offer survival advantage when compared to treatment at symptomatic relapse. However, this study pre-dates the use of PARPi maintenance treatment and the increased use of secondary cytoreductive surgery, so the results may be limited in their applicabili y to current practice. Limited evidence from one trial suggests that individualised nurse-led follow-up may improve HRQOL in women with ovarian cancer following completion of primary treatment. Large RCTs are needed to compare different types of follow-up, looking at survival, HRQOL, psychological effects, and cost as outcomes. (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Zagouri, F., et al. (2019). "Taxanes during pregnancy in cervical cancer: A systematic review and pooled analysis." Cancer Treatment Reviews 79: 101885.
	Background: Cervical cancer is one of the most common malignancies diagnosed during pregnancy. Taxanes administration has been established as theurapetic regimen in non pregrant women.; Objectives: This systemic review and meta-analysis aims to synthesize all available data from cervical cancer series in pregnant women and evaluate the efficacy and safety of taxanes during pregnancy.; Search Strategy: Eligible articles were identified by a search of ClinicalTrial.gov and MEDLINE databases for the period 01/01/2000 up to 31/11/2017; The algorithm consisted of a predefined combination of the words "cervical", "cancer", "taxanes" and "pregnancy".; Selection Criteria: PRISMA guidelines were applied in this study. The literature search and data extraction from all studies that examined the efficacy and safety of taxanes in pregnancy, were done by two independent investigators. Quantitative synthesis of the published articles was performed.; Data Collection and Analysis: Overall eight articles were retrieved. In all cases (14 pregnancies, 14 newborns) the use of taxanes in combination with platinum derivatives resulted in the birth of alive neonates, with not any miscarriage. The taxane derivative used in all cases was paclitaxel, combined with Cisplatin (13 pregnancies) and Carboplatin (one pregnancy).; Results: Complete and partial response was achieved in 7.2% and 92.9% of cervical cancer patients. In the majority of cases chemotherapy was well tolerated. The median progression-free survival was 48.5 months.; Conclusion: Taxanes administration during the 2nd and 3rd trimester of pregnancy is a safe choice. (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Zajec, V., et al. (2022). "Current status and challenges of drug development for hormonal treatment of endometriosis: a systematic review of randomized control trials." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(9): 713-720.
	Objective: The aim of this systematic review is to summarize the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on hormonal therapeutic options for endometriosis-associated pelvic pain (EAPP), excluding studies focusing on fertility.; Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 219 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, 11 primary articles met the inclusion criteria. A systematic review of the data was conducted.; Results: This review included several emerging drug therapies for EAPP. Randomized control trials showed promising results with several oral gonadotropin-releasing hormone antagonists (elagolix, relugolix, ASP1707, linzagolix). However, studies of other hormonal agents such as aromatase inhibitors and selective progesterone receptor modulators have not yielded significant or new advantages. Selective estrogen receptor modulators have not been represented in randomized control trials and have failed to demonstrate clinical efficacy.; Conclusion: Although numerous novel agents are being investigated for the treatment of endometriosis, there is still no significant progress in the development of curative rather than suppressive drugs. Therefore, further efforts are needed to develop an effective and hopefully curative treatment for this chronic, costly, and overwhelming disease.

Zakhari, A., et al. (2021). "Endometriosis recurrence following post-operative hormonal suppression: a systematic review and meta-analysis." Human Reproduction Update 27(1): 96-107.
	Background: Although surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical therapy in preventing recurrence of endometriosis following surgery.; Objective and Rationale: We performed a review of prospective observational studies and randomised controlled trials (RCTs) to evaluate the risk of endometriosis recurrence in patients undergoing post-operative hormonal suppression, compared to placebo/expectant management.; Search Methods: The following databases were searched from inception to March 2020 for RCTs and prospective observational cohort studies: MEDLINE, Embase, Cochrane CENTRAL and Web of Science. We included English language full-text articles of pre-menopausal women undergoing conservative surgery (conserving at least one ovary) and initiating hormonal suppression within 6 weeks post-operatively with either combined hormonal contraceptives (CHC), progestins, androgens, levonorgesterel-releasing intra-uterine system (LNG-IUS) or GnRH agonist or antagonist. We excluded from the final analysis studies with <12 months of follow-up, interventions of diagnostic laparoscopy, experimental/non-hormonal treatments or combined hormonal therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies.; Outcomes: We included 17 studies (13 RCTs and 4 cohort studies), with 2137 patients (1189 receiving post-operative suppression and 948 controls), which evaluated various agents: CHC (6 studies, n = 869), progestin (3 studies, n = 183), LNG-IUS (2 studies, n = 94) and GnRH agonist (9 studies, n = 1237). The primary outcome was post-operative endometriosis recurrence, determined by imaging or recurrence of symptoms, at least 12 months post-operatively. The secondary outcome was change in endometriosis-related pain. Mean follow up of included studies ranged from 12 to 36 months, and outcomes were assessed at a median of 18 months. There was a significantly decreased risk of endometriosis recurrence in patients receiving post-operative hormonal suppression compared to expectant management/placebo (relative risk (RR) 0.41, 95% CI: 0.26 to 0.65), 14 studies, 1766 patients, I2 = 68%, random effects model). Subgroup analysis on patients treated with CHC and LNG-IUS as well as sensitivity analyses limited to RCTs and high-quality studies showed a consistent decreased risk of endometriosis recurrence. Additionally, the patients receiving post-operative hormonal suppression had significantly lower pain scores compared to controls (SMD -0.49, 95% CI: -0.91 to -0.07, 7 studies, 652 patients, I2 = 68%).; Wider Implications: Hormonal suppression should be considered for patients not seeking pregnancy immediately after endometriosis surgery in order to reduce disease recurrence and pain. Various hormonal agents have been shown to be effective, and the exact treatment choice should be individualised according to each woman's needs. (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Zakhari, A., et al. (2020). "Post-operative dienogest following conservative endometriosis surgery: A systematic review and meta-analysis." J. Obstet. Gynaecol. Can. 42(5): 695-696.
	
Zakhari, A., et al. (2020). "Dienogest and the Risk of Endometriosis Recurrence Following Surgery: A Systematic Review and Meta-analysis." Journal of Minimally Invasive Gynecology 27(7): 1503-1510.
	Study Objective: To determine whether dienogest therapy after endometriosis surgery reduces the risk of endometriosis recurrence compared with expectant management.; Data Sources: Ovid MEDLINE, Ovid EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, clinicaltrials.gov, and International Standard Randomized Controlled Trial Number Registry were searched from inception to March 2019 for observational and randomized controlled trials.; Methods of Study Selection: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Medical Subject Heading terms and keywords such as "dienogest," "endometriosis," and "recurrence" were used to identify relevant studies.; Tabulation, Integration, and Results: The search yielded 328 studies, 10 of which were eligible for inclusion, representing 1184 patients treated with dienogest and 846 expectantly managed controls. Among these studies, 9 looked exclusively at endometrioma recurrence, whereas 1 used reappearance of symptoms as evidence of disease recurrence. Data on both incidence of and time to recurrence of endometriosis were extracted. The incidence rate of endometriosis recurrence in patients treated with dienogest was 2 per 100 women over a mean follow-up of 29 months (95% confidence interval [CI], 1.43-3.11) versus 29 per 100 women managed expectantly over a mean follow-up of 36 months (95% CI, 25.66-31.74). The likelihood of recurrence was significantly reduced with postoperative dienogest (log odds -1.96, CI, -2.53 to -1.38, p <.001).; Conclusion: Patients receiving dienogest after conservative surgery for endometriosis had significantly lower risk of postoperative disease recurrence than those who were expectantly managed. (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Zamorano, A., et al. (2021). "Low quality of life and activity levels persist in obese endometrial cancer survivors despite participation in a behavioral weight loss intervention." Gynecologic Oncology 162: S201.
	Objectives: Obesity is inversely related to quality of life (QOL) in endometrial cancer (EC) survivors. With over 600,000 EC survivors in the U.S., many women experience obesity‐related comorbidities following cancer cure, including poor QOL. We previously reported no change in weight after 6 months participation in a randomized trial comparing a text‐message‐based behavioral intervention and enhanced usual care (brief meeting, pamphlets with food diary). Here, we assessed changes in validated psychosocial (PS) measures between intervention groups. Based on previous literature, we also evaluated the effect of other factors (BMI, income, race, cancer stage, recurrence status) and hypothesized that these may predict improvement in QOL among EC survivors, over the intervention. Methods: EC survivors with a BMI ≥30kg/m2 participating in a randomized behavioral weight loss study in our gynecologic oncology clinic completed a survey of validated PS measures at baseline and at 6‐month study exit. These included the generalized mental and physical health QOL 12‐Item Short Form Health Survey (SF‐12; score 0‐100, higher numbers indicating better QOL), the International Physical Activity Questionnaire‐short form (IPAQ) to assess activity levels, and the Patient Health Questionnaire 9‐Item Version depression assessment (PHQ9; score 0‐27, higher scores indicating greater depression). The Kruskal‐Wallis test was used to identify significant changes. Results: Between May and December 2017, 80 women enrolled and completed the PS assessments. 42.5% of participants had a baseline BMI ≥40kg/m2, including 16.3% with a BMI ≥50kg/m2. Between intervention groups, there were no differences in mean scores or changes within any of the PS analyses. For all participants, median SF‐12 scores were at or below 50, consistent with generally low perceived QOL. Activity levels were low; at baseline, 26% reported no walking, 49% no moderate physical activity and 65% no vigorous physical activity within the last 7 days. Median total PHQ9 scores (5.5) were consistent with mild depression. Among all study participants, women with BMI ≥40kg/m2had a mean change from baseline in PHQ9 scores of ‐0.07 (±3.8) compared to ‐1.86 (±3.7) for BMI<40kg/m2(p=0.02). The change in SF‐12 physical health QOL scores in non‐WhiteWhite participants was 4.04 (±7.7) compared to ‐2.1 (±9.0) for WhiteWhite women (p=0.04), and 0.72 (±7.9) in early stage compared to ‐5.55 (±10.6) for Stages III‐IV (p=0.046).There were no differences in PS scores based on income or recurrence. Conclusions: A technology‐based behavior intervention did not improve QOL over enhanced usual care. Women with a BMI <40 kg/m2 had improvement in depression scores, and physical health QOL improved to a greater degree in early‐stage and non‐WhiteWhite participants. Overall, obese EC survivors remain minimally physically active, with generally low perceived QOL and mild depressive symptoms. Further studies aimed at improving QOL for this growing population of women are warranted.

Zander-Fox, D., et al. (2024). "Improved fertilization, degeneration and embryo quality rates with PIEZO-ICSI compared with conventional ICSI - A sibling oocyte split multi-center trial." Fertility and Sterility.
	OBJECTIVE: To investigate whether PIEZO-ICSI increases the fertilization rate, decreases the degeneration rate, and increases utilization rate per oocyte injected compared with conventional ICSI. DESIGN: Sibling oocyte split multi-centre trial. SETTING: Fertility clinics PATIENT(S): Women with a diagnosis of infertility utilizing ICSI as their method of insemination who have ≥ 6 mature oocytes for injection. INTERVENTION(S): Participants had their mature oocyte cohort divided, where half were injected using conventional ICSI and the other half were injected using PIEZO-ICSI. For patients with an uneven oocyte number the extra oocyte was injected using conventional ICSI. The injection technique utilized first was also randomized to ensure there was no bias due to order of injection. MAIN OUTCOME MEASURE(S): The primary outcome measure was fertilization rate post injection. RESULT(S): A total of 108 patients underwent a sibling split use of conventional ICSI and PIEZO-ICSI. The fertilization rate was 71.6% for PIEZO-ICSI, which was significantly increased compared with conventional ICSI 65.6% (p=0.028). In addition, oocyte degeneration rate was decreased in PIEZO-ICSI versus conventional ICSI (6.3% vs 12.1% respectively, p=0.002), and blastocyst quality was increased, as measured by the number of grade A and B quality blastocysts present on day 5 of development (33.3% vs 27.5% p=0.019). There were no significant differences found in aneuploidy rate, utilization rate, clinical pregnancy, or live birth outcome after single embryo transfer between the two injection techniques. CONCLUSION(S): This trial supports the possibility that PIEZO-ICSI increases fertilization, decreases oocyte degeneration rates and increases blastocyst quality compared with conventional ICSI, however, does not appear to influence the clinical pregnancy nor live birth rate per transfer.

Zander-Fox, D., et al. (2021). "PIEZO-ICSI increases fertilization rates compared with standard ICSI: a prospective cohort study." Reproductive Biomedicine Online 43(3): 404‐412.
	RESEARCH QUESTION: Is PIEZO‐intracytoplasmic sperm injection (ICSI) coupled with a new novel operational fluid (perfluoro‐n‐octane) superior to standard ICSI? DESIGN: A cohort of patients (n = 69) undertaking microinjection were recruited between January and November 2019 and were then prospectively case‐matched. Patients required six or more mature oocytes for inclusion in the study. PIEZO‐ICSI uses high‐speed microinjection drilling to penetrate the zona and oolemma and deposit the spermatozoa into the cytoplasm, compared with the traditional 'cutting' action of ICSI. The primary outcome was fertilization, with secondary outcomes including oocyte degeneration, abnormal fertilization, embryo cryopreservation and embryo utilization. RESULTS: PIEZO‐ICSI resulted in significantly higher fertilization rates (80.5 ± 2.4% vs 65.8 ± 2.3%, P < 0.0001) and lower oocyte degeneration rates (4.4 ± 1.3% vs 8.6 ± 1.2%, P = 0.019) and abnormal fertilization rates (2.9 ± 1.1% vs 7.4 ± 1.1%; P = 0.003) compared with standard ICSI. This improvement in fertilization was of most benefit in patients aged ≥38 years. This increase in fertilization increased the number of good quality embryos that were available for cryopreservation/transfer (3.8 ± 0.2 vs 3.1 ± 0.2; P = 0.038), such that patients on average had one extra usable embryo per cycle compared with standard ICSI. There were no differences to Day 5 embryo development or clinical pregnancy from fresh embryo transfer (57.1% PIEZO‐ICSI vs 60.0% ICSI) between microinjection methods, although pregnancy outcomes were underpowered. CONCLUSIONS: PIEZO‐ICSI significantly increased fertilization rates, thereby increasing the number of embryos available for cryopreservation compared with standard ICSI. Further prospective studies assessing cumulative pregnancy rates are warranted.

Zapico, A., et al. (2023). "Effect of Neuro-Adaptive Electrostimulation Therapy versus Sham for Refractory Urge Urinary Incontinence Due to Overactive Bladder: A Randomized Single-Blinded Trial." Journal of Clinical Medicine 12(3): 759.
	This randomized clinical trial evaluates the success rate of neuro-adaptive therapy (NAT), applied with a specific neuro-adaptive regulator device, the Self-Controlled Electro Neuro-Adaptive Regulation (SCENAR), versus a sham for urge incontinence due to an overactive bladder (OAB). From February 2019 to May 2021, 66 patients were recruited. All subjects were randomized 1:1 at the first intervention visit to the NAT or sham procedure. Inclusion criteria were females between 18 and 80 years old with leakages due to an overactive bladder with unresponsiveness to medical therapy. Subjects were scheduled to receive up to eight weekly 20 min intervention sessions to obtain a complete (CR) or partial response (PR). Patients with no response after three sessions were considered as a failure. The primary end point of this trial was to assess the efficacy of NAT compared to an inactive sham intervention, evaluated 1 month after the last session. Analysis showed 23 (70%) patients responded (20 complete and 3 partial response) in the NAT group compared to 16 (48%) patients (all complete response) in the placebo arm (p = 0.014). Significant differences were maintained after the intervention, with persistent response at 3 months in 19 (58%) patients after active treatment and 14 (42%) after the placebo (p < 0.001), and at 6 months in 18 (55%) vs. 11 (33%) (p = 0.022), respectively. The number of sessions to achieve CR was similar in both arms, with 4.3 +/- 1.9 in NAT and 3.9 +/- 1.8 in the sham group (NS). Significant differences were observed between both groups for patients' satisfaction (p = 0.01). The binary model selected age as a predictor of response at the last follow-up. The odds ratio indicates that each year of increase in age, the probability of a positive response to treatment at 6 months decreases 0.95 (95% CI 0.9-0.99) times (p = 0.03). In conclusion, this pilot randomized trial gives evidence that neuro-adaptive electrostimulation is effective to treat refractory urge urinary incontinence due to OAB. The security and long-term efficacy of this treatment merits further evaluation. Moreover, its favorable profile and the economic advantages of the device make the evaluation of this promising technique mandatory in a primary therapeutic scenario.Copyright © 2023 by the authors.

Zdroik, A., et al. (2024). "Injection site number and outcomes of intradetrusor onabotulinumtoxinA for refractory overactive bladder syndrome: a randomized clinical trial." International Urogynecology Journal 35(1): 119-126.
	Introduction and hypothesis: The optimal number of onabotulinumtoxinA injections for the treatment of refractory overactive bladder syndrome is unknown. Our primary objective was to determine whether 10-injections sites with 100 units of onabotulinumtoxinA each were associated with less pain than 20-injections sites. Method(s): In a single-blinded randomized trial, 100 units of onabotulinumtoxinA was administered, either as 10 x 1 ml or as 20 x 0.5 ml injections following the instillation of 30 ml of bupivacaine and 5 ml of NaHCO3 solution for 15 min. The primary outcome was procedural pain, as measured on an 11-point Numerical Pain Rating Scale (NPRS) immediately following the procedure. A power calculation estimated that 16 subjects in each arm were needed to detect a mean difference of 1 with a standard deviation of 1, on the NPRS score between the two treatment groups, with alpha 0.05 and power 80%. To adjust for an estimated 20% dropout rate, the final sample size was planned for 20 patients per group. Result(s): From October 2020 to November 2022, a total of 56 patients were approached and 40 were enrolled and randomized to two groups (21 in the 10-injections group and 19 in 20-injections group). The difference in the median pain score between the group was not statistically significant (4 [1.5-5] for 10 injections vs 3 [1-4] for 20 injections, p=0.823). Conclusion(s): Patients' perception of pain, efficacy, and adverse events did not significantly differ between patients receiving 10 and those receiving 20 injections of 100 units of onabotulinumtoxinA.Copyright © 2023, The International Urogynecological Association.

Zeng, L., et al. (2021). "[Systematic evaluation and sequential Meta-analysis of modified Xuefu Zhuyu Decoction combined with Western medicine in treatment of leiomyoma]." Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 46(1): 225-236.
	CNKI, PubMed and other databases were retrieved to extract eligible randomized controlled trial(RCT) about modified Xuefu Zhuyu Decoction(MXZD) combined with Western medicine(trial group) versus Western medicine alone(control group) in the treatment of leiomyoma. Therefore, a total of 25 RCTs were included, involving 2 328 patients. Bias risk evaluation tool in Cochrane Handbook 5.1.0 was used for evaluating the quality of these RCTs. Meta-analysis was performed for the reported indicators, including total efficiency, serum hormone level [progesterone(P), luteinizing hormone(LH), estradiol(E&#95;2), follicle stimulating hormone(FSH)], uterine size, fibroids size and adverse reactions by using Stata 14.0 software. Meta-analysis showed that the total efficiency(RR=1.21,95%CI[1.17,1.25],P&lt;0.05) of trial group was better than that of control group. Serum hormone level(WMD&#95;P=-3.86,95%CI[-4.31,-3.41],P&lt;0.05; WMD&#95;(LH)=-3.64,95%CI[-4.47,-2.82],P&lt;0.05; WMD&#95;(E&#95;2)=-39.99,95%CI[-53.45,-26.52],P&lt;0.05; WMD&#95;(FSH)=-3.79,95%CI[-4.86,-2.72],P&lt;0.05), uterine size(WMD=-50.02,95%CI[-55.98,-44.06],P&lt;0.05), fibroids size(WMD=-15.79,95%CI[-18.11,-13.46],P&lt;0.05) and adverse reactions(RR=0.65,95%CI[0.48,0.88],P&lt;0.05) of trial group were all lower than those of control group, with statistical significances. Trial sequential analysis(TSA) was performed by using TSA 0.9 software, and showed a reliable therapeutic effect of the experimental group. In short, our study indicated that modified Xuefu Zhuyu Decoction combined with Western medicine had a better therapeutic effect on leiomyoma than Western medicine alone, but more high-quality studies are needed to verify this conclusion in the future.

Zeng, L., et al. (2021). "Comparison of robotic-assisted versus conventional laparoscopy for para-aortic lymphadenectomy in gynaecological malignancies: A systematic review and meta-analysis."
	Types of study to be included No restrictions on the types of study design. Condition or domain being studied [1 change] The para-aortic lymphadenectomy (PAL) is an important step in the surgical staging of a variety of gynecologic malignancies, including endometrial, cervical, and ovarian cancers. The use of PAL may provide significant information on the spread and prognosis of cancer, allowing primary and adjuvant therapy to be targeted.4 Complex surgical treatments, such as PAL, can, however, have serious short- and long-term consequences, including the danger of developing intraperitoneal adhesions and radiation-related problems. Laparoscopic extraperitoneal PAL has been proved to be safe and feasible in several trials. The use of extraperitoneal laparoscopic PAL overcomes the traditional transperitoneal laparoscopic approach's poor exposure to the surgical field (due to obesity and overlaying bowel loops). However, the adoption of this technique was slower than predicted, with only a few locations adopting it. In fact, extraperitoneal laparoscopic PAL is a difficult technique that necessitates a steep learning curve and advanced endoscopic abilities. In the past few years, several studies have compared robot-assisted vs conventional laparoscopy for PAL in gynecological malignancies with limited evidence. Therefore, we perform a systematic review and meta-analysis for comparing the outcomes of robot-assisted versus conventional laparoscopy for PAL in gynecological malignancies. Participants/population [1 change] Inclusion Criteria: (a) Observational or interventional studies investigating for comparison of the outcomes for robot-assisted versus conventional laparoscopy for para-aortic lymphadenectomy in population with gynaecological malignancies in the published studies; (b) Availability of data for the outcomes including complication rates, total blood loss, length of hospital stay, total lymph node count) in both robotic and conventional laparoscopy groups; (c) population with gynaecological malignancies (endometrial cancer, cervical cancer, Ovarian Cancer) with aged > 18 years. Exclusion criteria: (a) Duplicate studies, case series, case reports, systematic reviews, conference abstracts, preprints, and editorials; (b) Studies that do not describe relevant outcomes; (c) Full texts are unavailable. Intervention(s), exposure(s) [1 change] Studies involving a comparison between robot-assisted vs conventional laparoscopy for para-aortic lymphadenectomy in gynecological malignancies Comparator(s)/control [1 change] Patients under conventional laparoscopy for para-aortic lymphadenectomy in gynecological malignancies Main outcome(s) [1 change] 1. To assess operating time, blood loss, and the number of lymph nodes harvested in robot-assisted vs conventional laparoscopy for para-aortic lymphadenectomy in gynecological malignancies 2. To assess complications rates in robot-assisted vs conventional laparoscopy for para-aortic lymphadenectomy in gynecological malignancies Measures of effect Risk Ratio or mean difference with 95% confidence i Additional outcome(s) [1 change] Subgroup analysis shall be conducted for transperitoneal and retroperitoneal approaches based on the availability of the data on the published studies Measures of effect Risk Ratio or mean difference with 95% confidence interval

Zeng, M., et al. (2022). "Paroxetine combined with traditional chinese medicine prescriptions in the treatment of postpartum depression: A systematic review of randomized controlled trials." Frontiers in Neuroendocrinology 67: 101019.
	Background: Postpartum depression is a common mental disease in obstetric puerperium. Its etiology is not completely clear, and its clinical manifestations are complex. It has serious adverse effects on the body and mind of mothers and infants. Treatment should also follow the principle of individualization. Preliminary studies have shown that traditional chinese medicine prescriptions combined with paroxetine is effective in treating postpartum depression. In order to better determine the therapeutic effect, further exploration was carried out.; Hypothesis: Does the study better evaluate the therapeutic effect and provide data support for clinical promotion?; Study Design: The search comes from using the following electronic databases established until January 2022.; Study Results: The meta analysis results show that paroxetine combined with traditional chinese medicine prescriptions can reduce the Hamilton Depression Scale (HAMD) score [WMD = -7.35, 95 % CI (-10.84, -3.87), P＜0.001] and Edinburgh Postpartum Depression Scale (EPDS) score [WMD = -3.24, 95 % CI (-5.96, -0.53), P &lt; 0.001].And better than paroxetine treatment alone in terms of improving clinical efficacy [RR = 1.22, 95 % CI (1.16, 1.30), P &lt; 0.001].; Conclusions: Based on the combination of paroxetine and traditional chinese medicine prescriptions in the treatment of postpartum depression, there is a certain clinical effect, and a strong research design and a certain number of RCTs are required at the same time. Future research should clarify the specific composition and composition of traditional Chinese medicine prescriptions.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Zeng, M. and L. Li (2019). "Single fresh blastocyst transfer or single cryopreserved-thawed blastocyst transfer: which is preferable for infertile patients in IVF/ICSI cycles? A meta-analysis." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 35(1): 17-22.
	Purposes: Nowadays, an increasing number of studies have proposed single embryo transfer (SET), especially single blastocyst transfer (SBT). To compare the clinical outcomes of single fresh blastocyst transfer (BT) and single cryopreserved-thawed BT in patients undergoing in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles.; Methods: The PubMed, Embase, and Cochrane Library databases were searched from the start dates until February 2018. The primary outcomes were clinical pregnancy rate (CPR) and embryo implantation rate (IR). The secondary outcomes were multiple pregnancy rate (MPR), live birth rate (LBR), and miscarriage rate (MR). Using the Mantel-Haenszel random effects model to analyze summary risk ratio (RR) with 95% confidence intervals (CIs). Statistical heterogeneity scores were assessed with the standard Cochrane's Q test and I 2 statistic.; Results: In total, eight studies (two prospective studies, six retrospective studies) were included in our analysis. There was no statistically significant difference regarding clinical pregnancy (RR = 1.18, 95% CI = 0.91-1.55) and embryo implantation (RR = 1.04, 95% CI = 0.77-1.41). Regarding secondary outcomes, there was no significant difference regarding miscarriage (RR = 0.79, 95% CI = 0.60-1.03) and multiple pregnancy (RR = 1.23, 95% CI = 0.75-2.04). However, single fresh BT is associated with an increased live birth (RR = 1.28, 95% CI = 1.05-1.57) compared with single cryopreserved-thawed BT.; Conclusions: In summary, this meta-analysis supports the hypothesis that single cryopreserved BT might not be the best choice compared with single fresh BT in patients undergoing IVF/ICSI cycles.

Zeng, M., et al. (2019). "Association of antinuclear antibody with clinical outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment: A meta-analysis." American journal of reproductive immunology (New York, N.Y. : 1989) 82(3): e13158.
	Problem: Several recent studies have investigated the relationship between antinuclear antibodies (ANAs) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. This meta-analysis evaluated the effect of ANA on clinical outcome for patients undergoing IVF/ICSI treatment.; Method of Study: A systemic survey of the literature was performed using PubMed, EMBASE and the Cochrane Library databases, through January 2019. Evaluated outcomes included clinical pregnancy rate (CPR), miscarriage rate (MR) and implantation rate (IR). Relative risk ratio (RR) and 95% confidence intervals (95% CI) were used for dichotomous data. Meta-analyses were performed with Review Manager 5.3 software.; Results: Eleven eligible studies were found. For IVF/ICSI cycles, compared with an ANA(-) group, infertile patients with ANA(+) had significantly reduced incidence of CPR (RR 0.66, 95% CI 0.56-0.79; I 2 = 60%) and IR (RR 0.61, 95% CI 0.49-0.76; I 2 = 75%), and had a higher MR (RR 1.81, 95% CI 1.40-2.36; I 2 = 48%).; Conclusion: This study suggested that ANA might cause poor pregnancy outcomes for infertile women undergoing IVF/ICSI treatment. (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Zeng, S., et al. (2023). "Efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent and refractory ovarian cancer: A systematic review and a meta-analysis." Frontiers in Pharmacology 14: 1111061.
	Objective: To explore the efficacy and safety of PD-1/PD-L1 inhibitors in treating recurrent/refractory ovarian cancer (OC). Methods: The online databases, including PubMed, Embase and Cochrane Library, were searched for relevant literatures on exploring the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The keywords are as follows: Ovarian neoplasms, programmed death receptor, PD-1, PD-L1, immunotherapy, and immune checkpoint inhibitor. Furthermore, qualified studies were screened for further meta-analysis. Results: In this study, 11 studies (990 patients) were analyzed to evaluate the efficacy of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The combined results proved that the objective response rate (ORR) was 6.7%, 95% CI (4.6%,9.2%), disease control rate (DCR) was 37.9%, 95% CI (33.0%, 42.8%), median overall survival (OS) was 10.70 months, 95% CI (9.23, 12.17), and median progression free survival (PFS) was 2.24 months, 95% CI (2.05, 2.43). In addition, in terms of the safety of patients suffering from recurrent/refractory OC and receiving PD-1/PD-L1 inhibitors, the combined treatment related adverse events (TRAEs) were 70.9% (61.7%-80.2%), and the combined immune related adverse events (iAEs) were 29%, 95% CI (14.7%, 43.3%). Conclusion: In patients with recurrent/refractory OC, PD-1/PD-L1 inhibitors were used alone and there was no obvious evidence of improved efficacy and survival. As for safety, the incidences of TRAEs and iAEs are high, so PD1/PD-L1 inhibitors should be applied according to individual conditions. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=367525, identifier CRD42022367525.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Zeng, Liu, Yu, Zou, Jin, Liu and Liu.)

Zeng, S., et al. (2022). "Efficacy and Safety of Minimally Invasive Surgery Versus Open Laparotomy for Interval Debulking Surgery of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A Systematic Review and A Meta-Analysis." Frontiers in Oncology 12: 900256.
	Objective: The selection of minimally invasive surgery (MIS) or open laparotomy for ovarian cancer (OC) after neoadjuvant chemotherapy still remains controversial. This study aimed to assess the efficacy and safety of MIS versus open laparotomy following neoadjuvant chemotherapy for advanced OC, so as to provide another option to select optimal surgical procedures for patients with OC.; Methods: Relevant literature studies about the risks of progression or mortality between women receiving MIS and open laparotomy for interval debulking surgery (IDS) were searched in the online databases, including PubMed, Embase, and the Cochrane Library with the following keywords: "ovarian neoplasms", "minimally invasive surgical procedures", "laparotomy", and "neoadjuvant therapy". Eligible studies were screened out for further meta-analysis.; Results: Six eligible literature studies, with 643 patients in the MIS group and 2,885 patients in the open laparotomy group, were included in this meta-analysis. No significant differences were detected in the overall survival (OS) of patients with OC who were treated with MIS or open laparotomy [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.59-1.23; heterogeneity: P = 0.051, I 2 = 57.6%]. However, the progression-free survival (PFS) was significantly higher in patients with OC treated with MIS than those treated with laparotomy (HR = 0.73; 95% CI = 0.57 to 0.92; heterogeneity: P = 0.276, I 2 = 22.4%). The completeness of debulking removal (R0 rate) in the open laparotomy group was not statistically higher compared with the control group (RR = 1.07; 95% CI = 0.93 to 1.23; heterogeneity: P = 0.098, I 2 = 52.3%), and no significant differences in residual disease of ≤1 cm (R1) (RR = 1.08; 95% CI = 0.91 to 1.28; heterogeneity: P = 0.330, I 2 = 12.6%) and postoperative complications were found between the two groups (RR = 0.72; 95% CI = 0.34 to 1.54; heterogeneity: P = 0.055, I 2 = 60.6%). Furthermore, the length of stays in hospital was significantly shorter in patients with OC treated with MIS than those treated with open laparotomy (Standard Mean Difference (SMD) = -1.21; 95% CI = -1.78 to -0.64; heterogeneity: P < 0.001, I 2 = 92.7%].; Conclusions: For IDS after NACT in patients with advanced OC, complete cytoreductive surgery with MIS is another feasible and effective choice.; Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022298519, identifier CRD42022298519.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Zeng, Yu, Cui, Liu, Jin, Li and Liu.)

Zeng, X., et al. (2023). "Open-label, phase 2, randomized controlled multicenter study comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in participants with homologous recombination deficient stage III/IV ovarian cancer: Trial in progress (1252)." Gynecologic Oncology 176(Supplement 1): S159-S160.
	Objectives: Maintenance therapy with niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been shown to extend progression-free survival (PFS) in patients with primary advanced ovarian cancer (OC) who responded to first-line platinum-based chemotherapy. The OPAL cohort C (OPAL-C) proof of concept study aims to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment versus standard of care in patients with advanced OC with homologous recombination-deficient (HRd) tumors. Method(s): OPAL-C (NCT03574779) is a global, multicenter, randomized, open-label, phase II trial. Eligible patients must have newly diagnosed stage III/IV, high-grade nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer and be eligible for neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery (IDS). Patients must have tumors that are HRd as determined by central testing using the Myriad myChoice CDx PLUS assay. Prior to study entry, patients must have completed 1 run-in cycle of carboplatin-paclitaxel. Patients will be randomized 1:1 to receive three 21-day cycles of neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response will then undergo IDS; patients with stable disease may undergo IDS at the investigator's discretion. Patients with disease progression will exit the study and be treated according to the investigator's discretion. After IDS, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy (addition of bevacizumab or bevacizumab biosimilar is optional), with the third cycle being optional. Subsequently, all patients will receive niraparib maintenance therapy (addition of bevacizumab or bevacizumab biosimilar is optional) for up to 36 months in the absence of progressive disease, death, unacceptable toxicity, or patient/physician decision to withdraw from the study. The primary endpoint is the pre-IDS unconfirmed response rate (RECIST v1.1 by investigator assessment), defined as the percentage of patients with an unconfirmed complete or partial response on study treatment before IDS. Secondary endpoints include the number of patients with CA-125 progression (per Gynecological Cancer InterGroup CA-125 response criteria), PFS, PFS rate at 12, 18, and 24 months, overall survival, and time to first-subsequent treatment. Exploratory endpoints include pathological complete response rate and biomarker evaluation. Safety and tolerability will also be assessed. An estimated sample size of 40 patients in each arm (80 patients total) is needed for the half-width of a 2-sided 80% CI of the pre-IDS unconfirmed response rate difference of 12%. This estimate assumes that the pre-IDS unconfirmed response rate in the neoadjuvant niraparib arm is 65%, and the pre-IDS unconfirmed response rate difference between arms is 20%. The study is currently enrolling, with planned study sites in Canada, Denmark, Spain, and the United States. Disclosures: This study was sponsored by GSK, Waltham, MA, USA.Copyright © 2023

Zesi, L., et al. (2021). "A comparison of the effects of bone marrow-derived stem cells and endometrial mesenchymal stem cells for Asherman Syndrome: a systematic review and meta-analysis."
	
Zesi, L., et al. (2021). "Efficacy and safety of stem cell-based therapy for the treatment of thin endometrium: A systematic review and meta-analysis."
	
Zeydan, B., et al. (2021). "Sleep quality and cortical amyloid-β deposition in postmenopausal women of the Kronos early estrogen prevention study." Neuroreport 32(4): 326‐331.
	Hormone therapy improves sleep in menopausal women and recent data suggest that transdermal 17β‐estradiol may reduce the accumulation of cortical amyloid‐β. However, how menopausal hormone therapies modify the associations of amyloid‐β accumulation with sleep quality is not known. In this study, associations of sleep quality with cortical amyloid‐β deposition and cognitive function were assessed in a subset of women who had participated in the Kronos early estrogen prevention study. It was a randomized, placebo‐controlled trial in which recently menopausal women (age, 42‐58; 5‐36 months past menopause) were randomized to (1) oral conjugated equine estrogen (n = 19); (2) transdermal 17β‐estradiol (tE2, n = 21); (3) placebo pills and patch (n = 32) for 4 years. Global sleep quality score was calculated using Pittsburgh sleep quality index, cortical amyloid‐β deposition was measured with Pittsburgh compound‐B positron emission tomography standard uptake value ratio and cognitive function was assessed in four cognitive domains 3 years after completion of trial treatments. Lower global sleep quality score (i.e., better sleep quality) correlated with lower cortical Pittsburgh compound‐B standard uptake value ratio only in the tE2 group (r = 0.45, P = 0.047). Better global sleep quality also correlated with higher visual attention and executive function scores in the tE2 group (r = ‐0.54, P = 0.02) and in the oral conjugated equine estrogen group (r = ‐0.65, P = 0.005). Menopausal hormone therapies may influence the effects of sleep on cognitive function, specifically, visual attention and executive function. There also appears to be a complex relationship between sleep, menopausal hormone therapies, cortical amyloid‐β accumulation and cognitive function, and tE2 formulation may modify the relationship between sleep and amyloid‐β accumulation.

Zhabitska, L. A. (2020). "Polycystic ovary syndrome: Individualized approach to treatment: Literature review." Reproductive Endocrinology(54): 89-94.
	Polycystic ovary syndrome (PCOS) is one of the most common causes of hyperandrogenism, menstrual irregularity and cardiometabolic dysfunction in women. The complete clinical picture includes irregular menstrual cycle, hirsutism, obesity, insulin resistance and anovulatory infertility. This article highlights the main issues for the PCOS definition, emphasizing its phenotypic heterogeneity. The main diagnostic criteria are given, which in turn determine the different phenotypes of this syndrome. To date, in order to improve the diagnosis and treatment of this syndrome, four different phenotypes have been identified, which include certain combinations of diagnostic criteria: 1) hyperandrogenism (clinical or biochemical) and chronic anovulation; 2) hyperandrogenism and polycystic ovaries on ultrasound, but with ovulatory cycles; 3) chronic anovulation and polycystic ovaries without hyperandrogenemia; 4) hyperandrogenemia, chronic anovulation and polycystic ovaries. This article presents the main groups of drugs that should be used in treatment of this pathology, according to the latest international guidelines, systematic reviews and meta-analyzes. In particular, indicated application features of insulin sensitizers and other antidiabetic drugs, glucagon-like peptide-1 analogues, oral contraceptives and progestins, antiandrogens. Particular attention is paid to the treatment choice depending on the phenotype and individual needs of patient. Therapeutic approach to the metabolic, hyperandrogenic and reproductive phenotype is covered separately. Anovulation or infrequent ovulation is a major cause of reproductive dysfunction in women with PCOS. The article lists the main methods and drugs that should be used to induce ovulation. In particular, the features of ovulation induction in women with clomiphene-resistance are considered. The cornerstone of treatment of women with PCOS and obesity with abdominal phenotype is a lifestyle modification, including diet and exercises. The clinical recommendations given in the article are based on the principles of evidence-based medicine.Copyright © 2020 Trylyst. All rights reserved.

Zhai, F., et al. (2019). "A comparison of the efficacy and safety of complementary and alternative therapies for the primary dysmenorrhea: A network meta-analysis protocol." Medicine 98(19): e15586.
	Background: There are a number of complementary and alternative therapies for the primary dysmenorrhea (PD) and their efficacy has been assessed by several systematic reviews. But only pair-wised drugs have been evaluated in the traditional meta-analyses and conflicting interpretation of results also existed among different studies. Here, a protocol for a network meta-analysis will be presented aimed to compare the efficacy and safety of different complementary and alternative therapies for PD.; Methods: All randomized controlled trials of complementary and alternative therapies for the PD will be included. The primary outcomes of our interest are pain intensity and pain duration and the secondary outcomes are quality of life, clinical effective rate, and adverse events. We will search relevant database, the ongoing trial, previous relevant reviews and reference lists, and so on. The identification and selection of studies and data extraction will be conducted by two independent reviewers. We will perform a battery of pairwise meta-analyses and Bayesian network meta-analyses to assess the relative outcomes of different complementary and alternative therapies. We will use the surface under the cumulative ranking curve values and the mean ranks to get the treatment hierarchy, and then use the node-splitting method to evaluate consistency. The softwares WinBUGS 1.4.3 and STATA will be selected and the quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument.; Ethics and Dissemination: This review does not require ethical approval.; Prospero Registration Number: PROSPERO CRD42018107763.

Zhang, C., et al. (2022). "Effect of Huposan Against Endometriosis: A Review." Chinese Journal of Experimental Traditional Medical Formulae 28(22): 257-264.
	EndometriosisEMsis a common chronic inflammatory gynecological disease,affecting about 5%-10% of women of childbearing age worldwide,and has always been a major challenge in clinical treatment. Huposan,derived from the Experiential Prescriptions for Universal Relief<< >>,has the effects of moving qi,activating blood,expelling blood stasis,and relieving pain. It is often used to treat EMs clinically and has achieved good curative effect. The relevant studies on the treatment of EMs by Huposan were retrieved from databases,such as CNKI,PubMed,Wanfang Data,and VIP for summarizing the mechanisms of action and clinical application of Huposan in the treatment of EMs,aiming to provide ideas and references for the basic research and clinical application of Huposan. As revealed by basic experiments,Huposan could exert therapeutic effects on EMs through resisting cell adhesion by reducing intercellular adhesion molecule 1 ICAM-1content,decreasing concentrations of matrix metalloproteinaseMMP-2 and MMP-9 against ectopic endometrial invasion,inhibiting vascular endothelial growth factorVEGFexpression for antiangiogenesis, inhibiting the expression of tumor necrosis factor-alphaTNF-alpha,interleukinIL-6,and IL-1,reversing helper T cellTh1/Th2 balance shifts to regulate the body's immune mechanism,and reducing the serum levels of nitric oxideNOand nitric oxide synthaseNOS. In clinic practice,Huposan has the effects of reducing ectopic lesions,relieving pain symptoms,reducing serum carbohydrate antigen 125CA125content,improving hormone levels,regulating endocrine and immune factors,and reducing postoperative recurrence rate. Huposan plays a therapeutic role in EMs through multiple targets and mechanisms,which is worthy of further exploration and clinical promotion.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Zhang, D.-F., et al. (2019). "Weekly cisplatin for the treatment of patients with ovarian cancer: A protocol for a systematic review of randomized controlled trial." Medicine 98(14): e15001.
	Background: Ovarian cancer (OC) is one of the most leading causes of deaths in the Chinese women. The objective of this protocol is to perform a full-scale systematic review on the efficacy of weekly cisplatin (WC) for the treatment of patients with OC.; Methods: Data sources will comprise of PubMed, PsycINFO, Scopus, Opengrey, Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All relevant randomized controlled trials from searched databases will be identified from their inception to the present. A defined search strategy will be implemented along with eligibility criteria. Relevant data will be extracted according to the predefined data collection form. Methodologic quality will be assessed by using Cochrane risk of bias tool; and data pooled and meta-analysis will be conducted by using fixed-effects, or random-effects model with RevMan 5.3 software.; Results: This proposed systematic review will evaluate the efficacy of WC for patients with OC.; Conclusion: The findings of this study may summarize the latest evidence for the WC on OC.; Ethics and Dissemination: Ethical approval is not required for this study, because it will be based on published studies, and existing sources of literature. The results of this study will be disseminated through peer-reviewed journal.; Prospero Registration Number: PROSPERO CRD42018120938.

Zhang, D.-F., et al. (2020). "Effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3: A protocol of systematic review and meta-analysis." Medicine 99(22): e20450.
	Background: This study will investigate the effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3 (HOCC-SKOV3).; Methods: We will retrieve potential studies from inception to the March 1, 2020 in Cochrane Library, MEDLINE, EMBASE, Scopus, Cumulative Index to Nursing and Allied Health Literature, WANGFANG, and China National Knowledge In-frastructure. There are not restrictions related to the language and publication status. This study will include case-controlled studies (CCSs) or randomized controlled studies (RCSs) that examine the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3. Two researchers will independently identify literatures, extract data, and appraise study quality. Any disagreements will be resolved by discussion with another researcher. RevMan 5.3 software will be placed to perform statistical analysis.; Results: This study will summarize the present evidence to test the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3.; Conclusion: It will provide evidence to investigate the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3, and will supply reference for further study.Systematic review registration: INPLASY202040146.

Zhang, G., et al. (2022). "Adjuvant chemoradiotherapy versus chemotherapy alone in stage III endometrial cancer: A systematic review and meta-analysis." The Journal of Obstetrics and Gynaecology Research 48(7): 1888-1896.
	Objective: To discuss the impact of chemoradiotherapy (CRT) on the survival of patients with stage III endometrial cancer (EC) compared with chemotherapy (CT) alone.; Methods: Articles involving adjuvant CRT versus CT on survival in stage III EC were retrieved from PubMed and EMBASE. Hazard ratios (HRs) of overall survival (OS) and relapse-free survival (RFS) were collected and pooled, and publication bias was measured by Begg's and Egger's test. Quality of researches was measured by the Newcastle-Ottawa scale and the modified Jadad scale.; Results: Eleven were included in the statistical analysis. A significant advantage of CRT over CT on OS was shown (HR 0.59, 95% CI 0.49-0.70). Further subgroup analysis suggested the advantage was mostly associated with stage IIIC (HR 0.63, 95% CI 0.52, 0.76]). A similar result favoring CRT was also reached on RFS (HR 0.66, 95% CI 0.47-0.93). No significant publication bias was observed.; Conclusion: CRT was associated with a better OS and RFS than CT alone in stage III EC patients. (© 2022 Japan Society of Obstetrics and Gynecology.)

Zhang, G., et al. (2019). "The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis." Journal of Ovarian Research 12(1): 33.
	Background and Objective: Previous studies about the prognostic value of the HIPEC have yielded controversial results. Therefore, this study aims to assess the impact of HIPEC on patients with ovarian cancer.; Results: We included 13 comparative studies, and found that the overall survival (OS) and progression-free survival (PFS) in HIPEC groups were superior to groups without HIPEC treatment in the all total population (HR = 0.54,95% CI:0.45 to 0.66, HR = 0.45, 95% CI: 0.32 to 0.62). Additionally, the subgroup analysis showed that patients with advanced primary ovarian cancers also gained improved OS and PFS benefit from HIPEC (HR = 0.59,95% CI:0.46 to 0.75, HR = 0.41,95% CI:0.32 to 0.54). With regard to recurrent ovarian cancer, HIPEC was associated with improved OS (HR = 0.45,95% CI:0.24 to 0.83), but for the PFS, no correlation was observed between HIPC group and the non-HIPEC group (HR = 0.55,95% CI:0.27 to 1.11). HIPEC also led to favorable clinical outcome (HR = 0.64,95% CI:0.50 to 0.82, HR = 0.36,95% CI:0.20 to 0.65) for stage III or IV ovarian cancer with initial diagnosis.; Conclusion: The review indicated that HIPEC-based regimens was correlated with better clinical prognosis for patients with primary ovarian cancers. For recurrent ovarian cancers, HIPEC only improved the OS but did not elicit significant value on the PFS.

Zhang, H., et al. (2023). "The role of metformin in the management of endometriosis: A systematic review and meta-analysis." Tropical Journal of Pharmaceutical Research 22(5): 1115-1120.
	Purpose: To analyze the activity of metformin in endometriosis, with a view to alleviating disease progression. Method(s): A search was conducted using electronic databases such as CNKI, VIP, CBM, WANFANG, Embase, PubMed, Cochrane, and Web of Science from January 1980 to January 2022 for randomized trials involving any intrapartum fetal surveillance method. A network meta-analysis was performed within a frequentist framework, and it was assessed for quality and network inconsistency of the trials. A ninety-five percent confidence interval (CI) was used to report the relationship between metformin levels and patients with endometriosis. Result(s): Eight eligible studies which included 688 patients were evaluated in this meta-analysis. The primary indicators were treatment efficiency and CA-125 level. Metformin significantly increased treatment efficiency (SMD = 3.29, 95 % CI 2.01, 5.40, p < 0.00001). As expected, metformin also reduced the CA-125 level in endometriosis patients as a result (Odds Ratio, OR = -1.20, 95 % CI: -1.40 - 1.00, p < 0.00001). Conclusion(s): Metformin alleviates pains caused by endometriosis. However, some studies had scanty information about alleviating clinical symptoms other than basic medical research. More randomized controlled trials are needed to confirm treatment efficacy.Copyright © 2023 University of Benin. All rights reserved.

Zhang, J., et al. (2020). "Effectiveness of different acupuncture for infertility: Overview of systematic reviews and network meta-analysis." European journal of integrative medicine 40: 101224.
	Introduction: Acupuncture may be an effective treatment option for infertility. Although there are several forms of acupuncture, there are no data that define which is the most suitable for infertility. The aim of this study was to conduct a network meta-analysis (NMA) to compare the effectiveness of various types of acupuncture used in the treatment of infertility. Method(s): Searches in seven databases were conducted and data from randomized controlled trials (RCTs) of acupuncture for infertility extracted and systematically reviewed. A measurement tool to assess systematic reviews 2 (AMSTAR2) was used to evaluate the quality of the systematic reviews(SRs). After conducting pairwise meta-analyses, NMA was used to compare the efficacy of the acupuncture treatment options. The risk of bias was assessed using the Cochrane risk of bias tool. Result(s): Twenty-four eligible RCTs (n=2095) were included in this review. The NMA data showed that warm acupuncture had the highest chances of increasing the rate of pregnancy (3 trials, 192 participants, RR=2.02,95%CI [(1.20,3.42)]) while acupuncture most positively affected the ovulation rate. On the other hand, a combination of acupuncture and moxibustion (1 trial, 62 participants, RR=1.89 (0.69, 3.09) had the most significant improvement in endometrial thickness and could reduce the rate of pregnancy loss. Conclusion(s): Compared with western medicine, acupuncture significantly increased the pregnancy and ovulation rates, as well as reducing the rate of miscarriages among Chinese women with infertility. Our NMA data demonstrated that warm acupuncture appears more effective in increasing the pregnancy rate.Copyright © 2020 Elsevier GmbH

Zhang, J., et al. (2020). "A comparison of the effects of Chinese non-pharmaceutical therapies for premature ovarian failure: A PRISMA-compliant systematic review and network meta-analysis." Medicine 99(26): e20958.
	Background: Premature ovarian failure (POF) is commonly treated with hormone replacement therapy (HRT). Many patients with POF choose acupuncture as a complementary therapy over HRT, due to possible adverse reactions. This systematic review and network meta-analysis (NMA) compares the efficacy of different forms of acupuncture therapies for POF.; Methods: Seven databases including PubMed, the Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure database, VIP Chinese Science, and Chinese Biomedical Database were searched for randomized controlled trials (RCTs) of various acupuncture treatments for POF. This time spanned from the date of database inception to January 13, 2020. RevMan 5.3 was used to assess the bias risk of the studies. A NMA of the included studies was performed using Stata14.0.; Results: A total of 408 items were searched in this study, and finally this NMA included 16 RCTS, involving 1,307 patients. It showed that acupuncture (OR:1.35,95%1.24 to 1.47) has the best effectiveness among the four acupuncture (standardized mean difference [SMD]-16.30,95% -31.33 to -1.28) is the most effective and the best in reducing follicle-stimulating hormone levels among the four acupuncture treatments. Acupuncture (SMD 26.67,95%5.95 to 47.40) and acupoint embedding (SMD41.14,95%11.90 to 70.37) were ranked in the top 2 positions, in improving estradiol, whereas acupuncture (SMD-4.90,95% -8.10 to -1.70) was than acupoint embedding and HRT, in reducing luteinizing hormone level. In addition, our conclusions have not changed significantly after the sensitivity analysis.Protocol registration number: CRD42020150508.; Conclusion: With clinical evidence summarized by NMA, it is observed that acupuncture is the most promising therapy for improving menopausal symptoms, decreasing serum follicle-stimulating hormone and luteinizing hormone level. Therefore, acupuncture could be effective for patients with POF, who are intolerant to the adverse effects of hormone replacement therapy or who would prefer non-drug therapies. Further multi-center and high-quality RCT studies should be conducted to make our conclusion more rigorous.

Zhang, J., et al. (2020). "A SYSTEMATIC REVIEW OF UTERINE-SPARING MINIMALLY INVASIVE TREATMENTS FOR FIBROID BLEEDING." Fertil. Steril. 114(3): e236-None.
	
Zhang, J., et al. (2021). "Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review." Reproductive Biology and Endocrinology 19(1): 142.
	Background: Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes. Method(s): A literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I2 statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019. Result(s): Ten eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26-1.60, P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17-2.13, P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20-1.66, P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer. Conclusion(s): The current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.Copyright © 2021, The Author(s).

Zhang, J., et al. (2023). "Effect of laparoscopic-assisted transvaginal hysterectomy on wound complications in patients with early stage cervical cancer: A meta-analysis." International wound journal.
	Laparoscopic-assisted vaginal radical hysterectomy (LARVH) and abdominal radical hysterectomy (ARH) have been widely applied to treat cervical carcinoma. But LARVH and ARH have not been fully investigated in treating cervical carcinoma after injury associated with injury. This research is intended to provide an up-to-date basis for comparing LARVH with ARH in early stage cervical carcinoma. Comparison between LARVH and ARH in cervical carcinoma was carried out through a combination of related research. Eligible articles from databases such as PubMed and Embase were screened using an established search strategy. This report covered the results of LARVH versus ARH in cervical carcinoma. The average difference and the 95% confidence interval (CI) were used for the combination of consecutive variables. The combination of categorical variables was performed with the odds ratio (OR) 95% confidence interval. Through the identification of 1137 publications, eight of them were chosen to be analysed. Among them, 363 were treated with LARVH and 326 were treated with ARH. Eight trials showed that LARVH was associated with a reduced risk of postoperative wound infection than ARH (OR, 0.23; 95% CI, 0.1-0.55, p = 0.0009). Five trials showed that there was no difference in the risk of postoperative bleeding after surgery (OR, 1.17; 95% CI, 0.42-3.29, p = 0.76). We also did not differ significantly in the duration of the surgery (OR, 1.79; 95% CI, -6.58 to 10.15, p = 0.68). So, the two surgical methods differ significantly only in the risk of postoperative wound infection. (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Zhang, J.-W., et al. (2023). "[Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis]." Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 48(21): 5946-5956.
	This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P&lt;0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P&lt;0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P&lt;0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P&lt;0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P&lt;0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

Zhang, L., et al. (2023). "Effects of Sitagliptin on Metabolic Indices and Hormone Levels in Polycystic Ovary Syndrome: a Meta-analysis of Randomized Controlled Trials." Reproductive sciences (Thousand Oaks, Calif.) 30(4): 1065-1073.
	To evaluate the effects of sitagliptin on the metabolic indices and hormone levels in patients with polycystic ovary syndrome (PCOS). PubMed, EMBASE, Web of Science, Cochrane Library, WanFang Data, and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) published up to March 2022. Eligible studies were identified based on the inclusion criteria. The primary outcomes included the homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone level (TT). Other outcomes included levels of sex hormones, glucose, and lipid metabolism. Forty-five studies were initially identified, and 6 RCTs with 394 patients were finally included in this study. The meta-analysis results suggest that sitagliptin improved HOMA-IR (WMD = - 0.35; 95% CI (- 0.62, - 0.08); P = 0.01), BMI (WMD = - 1.27; 95% CI (- 1.76, - 0.77); P < 0.00001), TT (SMD = - 0.66; 95% CI (- 1.25, - 0.07); P = 0.03), and HDL-C (SMD = 0.11; 95% CI (0.03, 0.18); P = 0.005). No significant differences were observed between the sitagliptin and control groups in other outcomes and in terms of adverse events. Evidence from meta-analyses suggests that sitagliptin was superior in improving insulin sensitivity, total serum testosterone, high-density lipoprotein, and body mass index. However, due to the limitations of published studies, it is difficult to draw a definite conclusion. Larger, higher-quality studies are needed to evaluate the efficacy of sitagliptin in women with PCOS. (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Zhang, L., et al. (2024). "Application of Four-Dimensional Pelvic Floor Ultrasound in the Diagnosis of Postpartum Pelvic Floor Dysfunction and Evaluation of Curative Effect." Alternative Therapies in Health and Medicine.
	Objective: To explore the application of four-dimensional pelvic floor ultrasound in the diagnosis of postpartum pelvic floor dysfunction (PFD) and evaluation of curative effect. Method(s): A total of 100 patients with postpartum PFD undergoing vaginal delivery in the hospital were enrolled as the research objects between January 2020 and January 2023. A total of 100 postpartum women with good pelvic floor muscle function during the same period were enrolled as a control group. Both groups underwent four-dimensional pelvic floor ultrasound detection. The bladder neck descent (BND), retrovesical angle (RVA), urethral tilt angle (UTA), urethral rotation angle (ROT), levator ani thickness under rest state (LATr), levator ani thickness under Valsalva state (LATs), levator ani hiatus area under rest state (LHAr) and levator ani hiatus area under Valsalva state (LHAs) in both groups were compared. The patients in the study group were given Kegel training for pelvic floor muscle rehabilitation exercise and bio-feedback electrical stimulation. According to the clinical curative effect, patients in the study group were divided into a recovery group (n=87) and a non-recovery group (n=13). The value of four-dimensional pelvic floor ultrasound in the diagnosis of PFD and evaluation of curative effect was analyzed. Result(s): In the observation group, BND, RVA, UTA, ROT, LHAr, and LHAs were higher, while LATr and LATs were lower compared to the control group. (P < .05). The results of ROC curves analysis showed that the AUC of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs in the diagnosis of PFD was 0.818, greater than that of the single index (0.728, 0.705, 0.680, 0.715, 0.677, 0.696, 0.719, 0.654; P < .05). BND, RVA, UTA, ROT, LHAr, and LHAs in the non-recovery group were higher than those in the recovery group, while LATr and LATs were lower than those in the recovery group (P < .05). The results of ROC curves analysis showed that the Area Under the Curve (AUC)of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs for predicting the curative effect were 0.804, greater than that of a single index (0.725, 0.653, 0.651, 0.744, 0.733, 0.720, 0.661, 0.718; P < .05). Conclusion(s): Four-dimensional pelvic floor ultrasound can be applied to intuitively evaluate the structure and function of postpartum pelvic floor tissues, which can provide a reliable basis for the diagnosis of postpartum PFD and evaluation of curative effect.

Zhang, L., et al. (2020). "Efficacy of paclitaxel, carboplatin, and bevacizumab for cervical cancer: A protocol for systematic review and meta-analysis." Medicine 99(24): e20558.
	Background: Cervical cancer (CC) is a very common and malignant tumor in female population. Although a variety of single medications are reported to treat this condition, they all have limited efficacy. Previous studies have reported the combination of paclitaxel, carboplatin, and bevacizumab (PCB) can be used for the treatment of patients with CC effectively. However, no systematic review has explored its efficacy and safety. This study will address its efficacy and safety systematically and comprehensively.; Methods: The following electronic databases will be retrieved from their inceptions to the January 1, 2020 to identify all potential associated studies: MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Google scholar, and Chinese Biomedical Literature Database. We will include randomized controlled trials (RCTs) of adult women (≥18 years) with CC globally. Eligible interventions will target any forms of PCB. The study methodological quality of all included studies will be appraised using Cochrane risk of bias tool. Statistical analysis will be undertaken using RevMan 5.3 software. In addition, we will perform a narrative synthesis to describe quality and content of the evidence.; Results: This study will summarize recent evidence and provide quality evidence for the efficacy and safety of PCB on CC.; Conclusion: The findings of this study will seek to identify the efficacy and safety of PCB and suggest future directions for research efforts targeting CC among this population.; Systematic Review Registration: INPLASY202040195.

Zhang, M.-M., et al. (2020). "The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials." Translational psychiatry 10(1): 193.
	Omega-3 fatty acids (FA), as a nutrient, has been proven effective in major depressive disorder (MDD), however, the results of monotherapy in perinatal depression (PND) remain unclear. To examine the efficacy and safety of omega-3 fatty acids (FA) monotherapy for perinatal depression (PND) compared with placebo. PubMed, Embase, PsycINFO, MEDLINE, Cochrane Library, and CINAHL were searched from inception up to November 2019. The reference lists of relevant review articles and included studies were also reviewed. Randomized placebo-controlled trials examining the efficacy and safety of omega-3 FA monotherapy in perinatal women with depressive symptoms were included. Pooled standard mean differences (SMD) were calculated and random-effects models were adopted for all analyses. Subgroups analyses and meta-regression were performed to quantify characteristics of the subjects and trials influencing the omega-3 response. In addition, meta-regression was conducted to identify the source of heterogeneity. The study protocol was registered at PROSPERO, CRD42020159542. Eight eligible randomized placebo-controlled trials were included involving 638 participants. There was a significant effect of omega-3 FA on perinatal depression. Omega-3 with higher ratio of EPA/DHA (≥1.5) had significant efficacy both in mild-to-moderate pregnant and postpartum depression with low incidence of side effects. Among the included trials reporting adverse effects, there was no significant difference in incidence of gastrointestinal and neurologic events between the omega-3 and placebo groups. There was no evidence of publication bias. Our findings suggested that omega-3 FA significantly improved depressive symptoms in perinatal women regardless of pregnant or postpartum and well-tolerated. Furthermore, the omega-3 response was linked to higher EPA proportion in omega-3 formula and mild- to-moderate depression.

Zhang, S., et al. (2021). "Ultrasound-guided percutaneous microwave ablation of adenomyosis: a narrative review." Annals of Palliative Medicine 10(11): 12003-12011.
	OBJECTIVE: The purpose of the present review is to analyze and summarize the feasibility, effectiveness, and safety of ultrasound-guided percutaneous microwave ablation (MWA) for adenomyosis according to largest studies available in current literature, so as to provide a more robust foundation for its use in the treatment of patients with this condition. BACKGROUND: Adenomyosis is a common and frequently occurring gynecological disease. It can lead to clinical symptoms such as dysmenorrhea, menostaxis, menorrhagia, and anemia, and can seriously affect patients' quality of life. Treatments for adenomyosis include drug, minimally invasive, and surgical therapies. Among them, ultrasound-guided percutaneous microwave ablation has become a new hotspot in the minimally invasive treatment of adenomyosis in recent years, with its advantages of small trauma and a good therapeutic effect. METHOD(S): Relevant studies were retrieved from the CNKI (Chinese National Knowledge Infrastructure), CQVIP, Wanfang, PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and Google Scholar databases. The retrieval time range was from January 2000 to June 2021. Chinese search terms included "adenomyosis", "microwave ablation", and "ultrasound". English search terms included "microwave ablation", "ultrasound", "(adenomyosis) OR (endometrioma) OR (adenomyoma)". CONCLUSION(S): Ultrasound-guided percutaneous microwave ablation therapy is a feasible, safe, and effective technique for the treatment of adenomyosis, and is worthy of clinical application and promotion.

Zhang Sandy, X. J., et al. (2023). "Ohnut Versus a Waitlist Control for the Self-management of Endometriosis-Associated Deep Dyspareunia: Protocol for a Pilot Randomized Controlled Trial." JMIR Research Protocols 12: e39834.
	Background: Endometriosis-associated deep dyspareunia is associated with reduced sexual quality of life, lower self-esteem, and impaired sexual function.; Objective: The primary objective is to assess the acceptability of a phallus length reducer (brand name: Ohnut [OhnutCo]), which is a buffer worn over the penis or a penetrating object to reduce endometriosis-associated deep dyspareunia, and the feasibility of a definitive randomized controlled trial (RCT). The secondary objective is to obtain estimates of the effectiveness of the buffer. An embedded substudy will explore the acceptability and the preliminary validity and reliability of a vaginal insert for the self-assessment of deep dyspareunia.; Methods: Ours is an investigator-initiated, 2-arm RCT. We will recruit 40 patient participants with diagnosed endometriosis between the ages of 19 and 49 years, as well as their sexual partners. The participating couples will be randomized in a 1:1 ratio into the experimental arm or the waitlist control arm. The length of the study period will be 10 weeks, during which time all participants will record deep dyspareunia severity following each episode of sexual intercourse. In weeks 1 to 4, all patient participants will record deep dyspareunia severity at each sexual encounter. In weeks 5 to 10, participants in the experimental arm will use the buffer during vaginal penetration; participants in the waitlist control arm will continue engaging in vaginal penetration as usual. Participants will complete questionnaires for assessing measures of anxiety, depression, and sexual function at baseline, at 4 weeks, and at 10 weeks. In the substudy, patient participants will self-assess dyspareunia by using a vaginal insert on 2 occasions, at least 1 week apart. The primary outcomes-the acceptability and feasibility of the buffer-will be assessed with descriptive statistics, and the secondary outcome-phallus length reducer effectiveness-will be assessed by using an analysis of covariance-based approach. For the vaginal insert, we will assess acceptability, test-retest reliability, and convergent validity via correlation analyses comparing the use of the insert to clinical examination in terms of dyspareunia assessment outcomes.; Results: Our pilot will provide initial data on the acceptability and effectiveness of the buffer and the feasibility of the study methodology. The results from our study are expected to be submitted for publication by the spring of 2023. As of September 2021, we have consented 31 couples into the study.; Conclusions: Our study will provide preliminary evidence for the self-assessment and management of endometriosis-associated deep dyspareunia. The findings will inform the decision to proceed to a definitive RCT.; Trial Registration: ClinicalTrials.gov NCT04370444; https://clinicaltrials.gov/ct2/show/NCT04370444.; International Registered Report Identifier (irrid): DERR1-10.2196/39834. (©Sandy X J Zhang, Rebecca G K MacLeod, Gurkiran Parmar, Natasha L Orr, Kate J Wahl, Heather Noga, Arianne Albert, Ryan Flannigan, Lori A Brotto, Paul J Yong. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 27.03.2023.)

Zhang, S. C., et al. (2023). "A Rapid Health Technology Assessment of Olaparib Applicated in Patients with Advanced Ovarian Carcinoma." Chinese Pharmaceutical Journal 58(1): 87-92.
	OBJECTIVE To evaluate the safety, efficacy and economics of olaparib in the treatment of patients with advanced ovarian cancer using rapid health technology assessment and provide evidence-based support for its clinical drug use. METHODS Relevant Chinese and English databases were searched systematically. Two researchers independently screened the literature, extracted the data, evaluated the quality and performed a comprehensive analysis according to the inclusion and exclusion criteria, and finally the results were summarized and analyzed by the method of qualitative description. RESULTS A total of 7 systematic reviews/Meta analyses and 9 pharmaeoeeonomic studies were included. The results showed that compared with conventional chemotherapy, olaparib had a lower incidence of adverse reactions in patients with advanced ovarian cancer. Compared with placebo, there were some mild or moderate adverse reactions, but they were easy to control. Olaparib could prolong PFS in patients compared with placebo and conventional chemotherapy, and it is worth noting that BRCA-positive patients have more clinical benefits. None of the included pharmaeoeeonomic studies showed olaparib advantages. CONCLUSION Olaparib has good safety and efficacy in the treatment of platinum-sensitive recurrent ovarian cancer. In the future, it is necessary to carry out its pharmaeoeeonomic research in China.Copyright © 2023 Chinese Pharmaceutical Association. All rights reserved.

Zhang, S.-S., et al. (2019). "Efficacy of robotic radical hysterectomy for cervical cancer compared with that of open and laparoscopic surgery: A separate meta-analysis of high-quality studies." Medicine 98(4): e14171.
	Background: To perform a meta-analysis of high-quality studies comparing robotic radical hysterectomy (RRH) vs laparoscopic radical hysterectomy (LRH), and open radical hysterectomy (ORH) for the treatment of cervical cancer.; Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed to identify studies that compared RRH with LRH or ORH. The selection of high-quality, nonrandomized comparative studies was based on a validated tool (methodologic index for nonrandomized studies) since no randomized controlled trials have been published. Outcomes of interest included conversion rate, operation time, intraoperative estimated blood loss (EBL), length of hospital stay (LOS), morbidity, mortality, number of retrieved lymph nodes (RLNs), and long-term oncologic outcomes.; Results: Twelve studies assessing RRH vs LRH or ORH were included for this meta-analysis. In comparison with LRH, there was no difference in operation time, EBL, conversion rate, intraoperative or postoperative complications, LOS, and tumor recurrence (P > .05). Compared with ORH, patients underwent RRH had less EBL (weighted mean difference [WMD] = -322.59 mL; 95% confidence interval [CI]: -502.75 to -142.43, P < .01), a lower transfusion rate (odds ratio [OR] = 0.14, 95% CI: 0.06-0.34, P < .01), and shorter LOS (WMD = -2.71 days; 95% CI: -3.74 to -1.68, P < .01). There was no significant difference between RRH and LRH with respect to the operation time, intraoperative or postoperative complications, RLN, and tumor recurrence (P > .05).; Conclusion: Our results indicate that RRH is safe and effective compared to its laparoscopic and open counterpart and provides favorable outcomes in postoperative recovery.

Zhang, W., et al. (2022). "Comparison of the effectiveness of sacrospinous ligament fixation and sacrocolpopexy: a meta-analysis." International Urogynecology Journal 33(1): 3-13.
	Introduction and Hypothesis: Sacrocolpopexy and sacrospinous ligament fixation (SSLF) have been used for the restoration of apical support. Studies comparing sacrocolpopexy and SSLF have reported conflicting results. We aim to assess the current evidence regarding efficiency and the complications of sacrocolpopexy compared with SSLF.; Methods: We searched PubMed, Embase, and Cochrane Library and performed a systematic review meta-analysis to assess the two surgical approaches.; Results: 5Five randomized controlled trials, 8 retrospective studies, and 2 prospective studies including 4,120 cases were identified. Compared with abdominal sacrocolpopexy (ASC), SSLF was associated with a lower success rate (88.32% and 91.45%; OR 0.52; 95% CI 0.29-0.95; p = 0.03), higher recurrence (11.58% and 8.32%; OR 1.97; 95% CI 1.04-3.46; p = 0.04), and dyspareunia rate (14.36% and 4.67%; OR 3.10; 95% CI 1.28-7.50; p = 0.01). Patients in this group may benefit from shorter operative time (weighted mean difference -25.08 min; 95% CI -42.29 to -7.88; p = 0.004), lower hemorrhage rate (0.85% and 2.58%; OR 0.45; 95% CI 0.25-0.85; p = 0.009), wound infection rate (3.30% and 5.76%; OR 0.55; 95% CI 0.39-0.77; p = 0.0005), and fewer gastrointestinal complications (1.33% and 6.19%; OR 0.33; 95% CI 0.15-0.76; p = 0.009).; Conclusion: Both sacrocolpopexy and SSLF offer an efficient alternative to the restoration of apical support. When anatomical durability and sexual function is a priority, ASC may be the preferred option. When considering factors of mesh erosion, operative time, gastrointestinal complications, hemorrhage, and wound infections, SSLF may be the better option. (© 2021. The Author(s).)

Zhang, X., et al. (2021). "The clinical efficacy of Jinfeng pill in the treatment of thin endometrial infertility: a systematic review and meta-analysis." Annals of Palliative Medicine 10(12): 12529-12537.
	Background: To systematically evaluate the clinical efficacy of Jinfeng pill in the treatment of patients with thin endometrial infertility.; Methods: The databases of PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Wanfang Science and Technology Journal Full-text Database, and Chinese Biomedical Literature Database (CBM) were used to search for articles related to Jinfeng pills in the treatment of thin endometrial infertility from database establishment to September 2021. Duplicate articles were eliminated through Endnote X9 software. Data were recorded using Stata 15.1 software, and a meta-analysis of the results was performed using fixed or random-effects models for pregnancy rate, abortion rate, endometrial thickness, and endometrial morphology type A. A funnel plot was used to evaluate the publication bias of the included literature. Article heterogeneity was judged by the I2 test, suggesting clear heterogeneity when I2>50%, and sensitivity analysis by excluding studies when the heterogeneity was too high.; Results: Finally, 3 articles were included. Meta-analysis showed that the pregnancy rate in the trial group was significantly higher than that in the control group; the abortion rate in the trial group was significantly lower than that in the control group; the endometrial thickening in the trial group was significantly greater than that in the control group, the above three results were statistically different. Regarding the issue of endometrial type, the results showed that there was no significant difference between the 2 groups, and the difference was not statistically significant. The funnel plot results of pregnancy rate showed that the scatter was asymmetric, suggesting that there may have been publication bias.; Discussion: Jinfeng pill can effectively improve the clinical symptoms of thin endometrial infertility, improve the pregnancy rate, reduce the abortion rate, and improve endometrial thickness, However, due to the small number of included articles and the quality of included studies, our conclusion requires verification through a larger sample and a higher quality clinical study.

Zhang, X.-W., et al. (2022). "Acupuncture for cancer-related conditions: An overview of systematic reviews." Phytomedicine : international journal of phytotherapy and phytopharmacology 106: 154430.
	Background: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically.; Objective: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies.; Methods: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description.; Results: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported.; Conclusion: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.; Competing Interests: Declaration of Competing Interest No publication by our team was included, and there is no other conflict of interest as well. (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Zhang, Y., et al. (2020). "Effects of arsenic trioxide combined with platinum drugs in treatment of cervical cancer: A protocol for systematic review and meta-analysis of randomized controlled trials." Medicine 99(45): e22950.
	Introduction: Cervical cancer is the second largest tumor disease threatening female reproductive tract health. AS2O3 is a multi-directional and multi-target anti-cervical cancer drug. It can be combined with platinum drugs to treat cervical cancer. The literatures of AS2O3 combined with platinum drugs related to cervical cancer have shown inconsistent results, and there is currently no high quality of systematic review to evaluate the effects of AS2O3 combined with platinum drugs in cervical cancer patients.; Methods and Analysis: English and Chinese literature about AS2O3 combined with platinum drugs treatment for cervical cancer published before August 31, 2020 will be systematic searched in PubMed, Embase, Web of Science, Cochrane Library, Open Grey, Clinicaltrials.gov, Chinese Clinical Trial Registry, WANFANG, VIP Chinese Science and Technology Journal Database, CNKI, Chinese biomedical document service system (SinoMed). Only randomized controlled trials (RCTs) of patients with cervical cancer will be included. Literature screening, data extraction, and the assessment of risk of bias will be independently conducted by 2 reviewers, and the 3rd reviewer will be consulted if any different opinions existed. Clinical total effective rate, adverse events, SCCAg, CYFRA21-1, quality of life, and immune function will be evaluated. Systematic review and meta-analysis will be produced by RevMan 5.3 and Stata 14.0. This protocol reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement.; Results: The current study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings in the fourth quarter of 2021.; Conclusion: Efficacy and safety of AS2O3 combined with platinum drugs in the treatment of cervical cancer will be assessed. The results will be published in a public issue journal to provide evidence-based medical evidence for Obstetrician and Gynecologists to make clinical decisions.; Ethics and Dissemination: Ethical approval is not required as the review is a secondary study based on published literature. The results of the study will be published in peer-reviewed publications and disseminated electronically or in print.; Protocol Registration Number: INPLASY202080130.

Zhang, Y., et al. (2022). "Impact of cystectomy versus ablation for endometrioma on ovarian reserve: a systematic review and meta-analysis." Fertility and Sterility 118(6): 1172-1182.
	Objective: To investigate whether cystectomy or ablation for endometrioma has less impact on ovarian reserve as evaluated by antral follicle count (AFC) and antimüllerian hormone (AMH) levels.; Design: Systematic review and meta-analysis.; Setting: Not applicable.; Patient(s): Patients with endometriomas undergoing cystectomy or ablation.; Intervention(s): All prospective studies comparing cystectomy with ablation for endometrioma in the PubMed, EMBASE, MEDLINE and Web of Science until April 3, 2022 were retrieved and reviewed. Medical treatment used as adjuvant therapy for the surgery was excluded. Two authors assessed eligibility and risk of bias independently. The statistical data were pooled using the Review Manager software.; Main Outcome Measure(s): The changes of AMH levels and AFC values in cystectomy group and ablation group, including intergroup comparisons and intragroup comparisons.; Result(s): Four randomized clinical trials and 2 prospective cohort studies were eligible for the meta-analysis, with a total of 294 patients. In the intergroup comparisons, preoperative AFC values were similar with low heterogeneity, but postoperative AFC values were significantly lower in cystectomy than ablation (mean differences [MD], -1.33; 95% credible interval, -2.15 to -0.51; I 2 = 57%). In the intragroup comparisons of AFC values, sensitivity analyses showed a significant decrease in cystectomy (MD, -1.93; 95% credible interval, -2.40 to -1.45; I 2 = 0%) at 6-month follow-up, compared with no reduction in ablation. The intragroup comparisons of AMH levels supported negative effects on ovarian reserve of both cystectomy (MD, -1.26; 95% credible interval, -1.64 to -0.88; I 2 = 45%) and ablation (MD, -0.70; 95% credible interval, -1.07 to -0.32; I 2 = 0%).; Conclusion(s): Both ablation and cystectomy have significantly detrimental effects on ovarian reserve as evaluated by AMH, but the ablation causes relatively less damage to ovarian reserve as appraised by AFC.; Clinical Trial Registration Number: CRD42020152823;PROSPERO (york.ac.uk). (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Zhang, Y., et al. (2022). Is moxibustion safe and effective in treating female stress urinary incontinence? A systematic review and meta-analysis, Research Square.
	Background Stress urinary incontinence (SUI) in women is a female urogenital disease in which urine leaks out involuntarily due to increased abdominal pressure during coughing or sneezing or physical activity. As one of complementary and alternative medicine, moxibustion therapy has been widely used in the clinical treatment of female SUI, but its efficacy and safety have not been systematically evaluated. Therefore, this study aimed to systematically evaluate the efficacy and safety of moxibustion in the treatment of female SUI.Methods The following electronic databases were searched from database establishment to December 2021: PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database, and China Biology Medicine Disc (CBM). All randomized controlled trials (RCTs) with moxibustion as an intervention for the treatment of female SUI were included in this study. The primary outcome of included studies was the change from baseline in urine leakage measured by the 1-hour pad test. Secondary outcomes included clinical efficacy, the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) score, mean 24-hour frequency of incontinence episodes, and adverse events. The meta-analysis was performed by STATA software (version 15.0) in this study.Results A total of 13 RCTs were included in this meta-analysis, involving 822 female SUI patients, of which 413 in the experimental group received moxibustion, and 409 in the control group received other conservative treatments (pelvic floor muscle training or acupuncture or Chinese medicine). The results of the meta-analysis showed that compared with receiving pelvic floor muscle training (PFMT) or acupuncture or Chinese medicine treatment, moxibustion intervention for female SUI reduced urine leakage in the one-hour pad test [SMD=-0.86, 95%CI (-1.03,-0.58)], significantly improved clinical efficacy [OR&amp;thinsp;=&amp;thinsp;3.42, 95%CI (2.32,5.04)], decreased the ICIQ-SF score [SMD=-0.80, 95%CI (-1.03,-0.57)], and reduced average 24-hour incontinence episode frequency [SMD=-0.78, 95%CI (-1.05,-0.54)]. At the same time, no adverse events occurred during the moxibustion intervention.Conclusions Based on this meta-analysis, moxibustion, as one of the complementary and alternative medicine therapies, can be effective and safe in the treatment of female SUI. Moxibustion intervention can reduce urine leakage in the one-hour pad test, improve clinical efficacy, reduce the ICIQ-SF score, and reduce the average 24-hour frequency of urinary incontinence episodes. However, due to the low quality of evidence in this study, higher-quality RCTs are needed for further demonstration.Registration of systematic review: This systematic review and meta-analysis has been registered in the INPLASY International Registry of Prospective Systematic Reviews under the registration number INPLASY2021120052.

Zhang, Y. F., et al. (2022). "Cervical Cancer Recurrence and Patient Survival After Radical Hysterectomy Followed by Either Adjuvant Chemotherapy or Adjuvant Radiotherapy With Optional Concurrent Chemotherapy: A Systematic Review and Meta-Analysis." Frontiers in Oncology 12: 823064.
	Objective: To compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or without concurrent chemotherapy (AR/CCRT). Method(s): We systematically searched PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov to identify studies reporting recurrence or survival of cervical cancer patients who received AC or AR/CCRT after radical hysterectomy. Data were meta-analyzed using a random-effects model, and heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. Result(s): The meta-analysis included 14 non-randomized studies and two randomized controlled trials, altogether involving 5,052 cervical cancer patients. AC and AR/CCRT groups did not differ significantly in rates of total or local recurrence or mortality. Nevertheless, AC was associated with significantly lower risk of distant recurrence [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.55-0.81] and higher rates of overall survival [hazard ratio (HR) 0.69, 95%CI 0.54-0.85] and disease-free survival rate (HR 0.77, 95%CI 0.62-0.92). Conclusion(s): AC may be an effective alternative to AR/CCRT for cervical cancer patients after radical hysterectomy, especially younger women who wish to preserve their ovaries and protect them from radiation damage. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021252518).Copyright © 2022 Zhang, Fan, Zhang, Ruan, Mu and Li.

Zhang, Y.-F., et al. (2022). "Reproductive and oncological outcomes of fertility-sparing surgery in patients with stage I epithelial ovarian cancer: A systematic review and meta-analysis." Medicine 101(31): e29929.
	Objective: We meta-analyzed available evidence on fertility, survival, and cancer recurrence in patients with stage I epithelial ovarian cancer (EOC) after fertility-sparing surgery (FSS).; Methods: We systematically reviewed PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify studies reporting reproductive and oncological outcomes of patients with stage I EOC who underwent FSS. Random-effects models were used to calculate pooled rates of disease outcomes, along with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify sources of heterogeneity in the data.; Results: We included 23 observational retrospective studies involving 1126 patients. The pooled pregnancy rate was 30% (95% CI, 0.26-0.34), while the pooled natural conception rate was 26% (95% CI, 0.20-0.33). The pooled live birth rate was 27% (95% CI, 0.22-0.32). The pooled rate of EOC recurrence was 12% (95% CI, 0.09-0.14), which did not differ significantly from the rate among patients who underwent radical surgery (odds ratio, 0.77; 95% CI, 0.45-1.33).; Conclusions: FSS is associated with good oncological outcomes but less than satisfactory reproductive outcomes. All in all, the procedure appears to be a safe alternative to radical surgery for EOC patients who want to preserve fertility.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zhang, Z.-Y., et al. (2020). "Effectiveness of neuromuscular electrical stimulation for endometriosis-related pain: A protocol of systematic review and meta-analysis." Medicine 99(25): e20483.
	Background: This study will assess the effectiveness and safety of neuromuscular electrical stimulation (NMES) for endometriosis-related pain (ERP).; Methods: Seven electronic databases of Cochrane Library, PUBMED, EMBASE, WANGFANG, VIP, CBM, and CNKI will be searched. We will search all electronic databases related the randomized controlled trials (RCTs) on the effectiveness and safety of NMES for ERP up to the March 31, 2020 without restrictions of language. RevMan 5.3 software will be used for risk of bias assessment, related data analysis and meta-analysis.; Results: This systematic review and meta-analysis will summarize current high-quality RCTs on the effectiveness and safety of NMES for ERP. Results of this study will provide the basis for both clinician and further research.; Conclusion: This study will investigate whether NMES is effective and safety for the treatment of ERP.; Systematic Review Registration: INPLASY202040191.

Zhao, D.-X., et al. (2020). "Efficacy of weekly paclitaxel for the treatment of advanced ovarian cancer: A protocol for systematic review and meta-analysis." Medicine 99(25): e20537.
	Background: This study aims to assess the efficacy and safety of weekly paclitaxel (WP) for the treatment of advanced ovarian cancer (AOC).; Methods: This study will systematically search bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, PSYCINFO, Allied and Complementary Medicine Database, CNKI, WANGFANG, and Chinese Biomedical Literature Database) and other literature sources from inception to the March 1, 2020 without language and publication time limitations. Two authors will independently complete all literature selection, data collection, and study quality evaluation. Any disagreements will be solved by a third author through discussion. We will analyze data by RevMan V.5.3 software.; Results: This study will systematically generate a comprehensive summary on the efficacy and safety of WP for the treatment of AOC.; Conclusion: This study may provide beneficial evidence of WP for the treatment of AOC.; Systematic Review Registration: INPLASY202040193.

Zhao, F.-Y., et al. (2021). "Acupuncture as an Independent or Adjuvant Management to Standard Care for Perimenopausal Depression: A Systematic Review and Meta-Analysis." Frontiers in Psychiatry 12: 666988.
	Background: Many women with perimenopausal depression (PMD) have sought alternative therapies such as acupuncture because of concerns about risks associated with antidepressant and hormone replacement therapy (HRT). This systematic review aimed to clarify if acupuncture is effective for PMD compared with waitlist control or placebo/sham acupuncture, and if acupuncture alone or combined with standard care (antidepressant and/or HRT) is more effective in ameliorating PMD in comparison with standard care alone. Methods: Randomized controlled trials (RCTs) of PMD treatment via acupuncture vs. waitlist control or placebo/sham acupuncture, and RCTs of PMD treatment via acupuncture alone or combined with Western pharmacotherapy vs. Western pharmacotherapy were searched for from seven databases from inception to December 2020. Cochrane criteria were followed. Results: Twenty-five studies involving 2,213 women were analyzed. Meta-analyses indicated that acupuncture significantly reduced the global scores of Hamilton Depression Scale (HAMD) [standardized mean difference (SMD) = -0.54, 95% CI (-0.91, -0.16), p < 0.01], compared with standard care. The therapeutic effect of acupuncture maintained at 2-, 4-, and 12-week follow-ups. Acupuncture combined with standard care was more effective than standard care alone in decreasing HAMD scores [SMD = -0.82, 95% CI (-1.07, -0.58), p < 0.01]. Too few RCTs were available to assess the clinical efficacy differences between acupuncture and placebo/sham acupuncture or HRT alone. Acupuncture also showed better effects in decreasing Kupperman index (KI) scores, whether compared with antidepressant alone [MD = -4.55, 95% CI (-8.46, -0.65), p = 0.02] or antidepressant combined with HRT [MD = -0.89, 95% CI (-1.34, -0.43), p < 0.01]. Conclusions: In comparison with standard care, acupuncture alone or combined with standard care was associated with significant improvements in PMD and reductions of other menopausal symptoms. This finding suggests that acupuncture may be a useful addition to treatment for PMD.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Zhao, Fu, Kennedy, Conduit, Zhang and Zheng.)

Zhao, H., et al. (2019). "Neoadjuvant chemotherapy with radical surgery vs radical surgery alone for cervical cancer: a systematic review and meta-analysis." OncoTargets and therapy 12: 1881-1891.
	Aim: This systematic review was designed to evaluate the efficacy of neoadjuvant chemotherapy with radical surgery vs radical surgery alone for cervical cancer.; Methods: A computerized search was done for trials from PubMed, EMBASE, CENTRAL, and Cochrane Database of Systematic Reviews. The trials included neoadjuvant chemotherapy plus radical surgery vs radical surgery alone. We measured overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), local and distant recurrence, lymph node metastasis, and parametrial infiltration per patient.; Results: In all, 13 studies involving 2,158 subjects were included. In regard to OS, DFS, PFS, local and distant recurrence, and parametrial infiltration, neoadjuvant chemotherapy plus radical surgery was similar to radical surgery alone. Among them, subgroup analysis of eight studies involving 1,544 patients with locally advanced cervical cancer (FIGO stage IB2-IIB) showed that neoadjuvant chemotherapy (NACT) plus radical surgery significantly improved OS, and decreased local and distant recurrence rates, lymph node metastasis rate, and the level of parametrial infiltration compared to radical surgery alone.; Conclusion: The present study demonstrates that preoperative NACT is now an accepted effective procedure in selected patients with locally advanced cervical cancer (FIGO stage IB2-IIB). However, the relationship between NACT and longer DFS and PFS cannot be demonstrated by this meta-analysis. Thus, the decision to use or not to use NACT before radical surgery depends on the surgeon's experience and clinical judgment. Nevertheless, further research in this field is urgently needed to confirm it.; Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Zhao, H., et al. (2023). "Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment." Journal of Ovarian Research 16(1): 9.
	Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overabundance of androgens; it affects 6-20% of women of reproductive age. PCOS involves various pathophysiological factors, and affected women usually have significant insulin resistance (IR), which is a major cause of PCOS. IR and compensatory hyperinsulinaemia have differing pathogeneses in various tissues, and IR varies among different PCOS phenotypes. Genetic and epigenetic changes, hyperandrogenaemia, and obesity aggravate IR. Insulin sensitization drugs are a new treatment modality for PCOS. We searched PubMed, Google Scholar, Elsevier, and UpToDate databases in this review, and focused on the pathogenesis of IR in women with PCOS and the pathophysiology of IR in various tissues. In addition, the review provides a comprehensive overview of the current progress in the efficacy of insulin sensitization therapy in the management of PCOS, providing the latest evidence for the clinical treatment of women with PCOS and IR.Copyright © 2023, The Author(s).

Zhao, J., et al. (2023). "Effects of selenium supplementation on Polycystic Ovarian Syndrome: a systematic review and meta-analysis on randomized clinical trials." BMC Endocrine Disorders 23(1): 33.
	Background: This study provides a systematic review and meta-analysis of randomized controlled trials, which examined the effect of the selenium supplementation on polycystic ovary syndrome (PCOS).; Methods: Confirmed studies related to selenium supplementation and PCOS were searched from the databases of EMBASE, PubMed and Web of Science. Data were reported as weighted mean difference (WMD) or standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis was performed with Stata version 12.0.; Results: A total of 389 cases (selenium group n = 195, control group n = 194) were included in this studies. This meta-analysis showed that selenium supplementation has a positive effect on TAC, and supplementation of selenium does not significantly improve the level of BMI, Weight, LDL, HDL, Triglycerides, Total Testosterone, HOMA-IR, NO, GSH, MDA and FPG.; Conclusion: Although selenium can improve TAC in PCOS patients, it has no significant effect on BMI, Total Testosterone, et al. In terms of the results of this meta-analysis, it is not recommended for patients with PCOS to use selenium as a regular trace element supplement. Based on the improving effect of selenium on TAC, supplementation of selenium may have a positive effect on improving follicle quality for some PCOS patients who have poor follicle quality caused by oxidative stress or who want to undergo IVF. (© 2023. The Author(s).)

Zhao, J., et al. (2020). "The Effect of Metformin Therapy for Preventing Gestational Diabetes Mellitus in Women with Polycystic Ovary Syndrome: A Meta-Analysis." Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 128(3): 199-205.
	Objective: This study was to analyze the efficacy of metformin intervention in preventing gestational diabetes mellitus (GDM).; Methods: A systematic review and meta-analysis of clinical trials or observational studies of metformin intervention in preventing symptoms of GDM during pregnancy were performed. Medline, Embase, and Cochrane Library were searched through to now. The main evaluated primary outcomes were incident of GDM, miscarriage, preterm delivery, and neonatal mortality. The evaluated secondary outcomes were mean difference of gestational age at birth and birth weight between metformin group and control group.; Results: We included 6 studies including 3 randomized clinical trials (RCTs), 2 observational studies, and 1 non-RCT in our meta-analysis. A total of 643 patients were enrolled for a follow-up study with continued metformin therapy (n=341) or not (n=302) during pregnancy. Metformin therapy reduced the proportion of patients developing GDM (log Odds Ratio: -1.27; 95%CI: -2.24 to -0.30) but had no significant effect on reducing the proportion of abortion, preterm delivery, and neonatal death in pregnant women with polycystic ovary syndrome (PCOS). Also, it did not cause a significant difference in gestational age at birth and birth weight in metformin group versus control/placebo group.; Conclusions: Metformin was associated with less frequent GDM development than control diets, suggesting that it is the appropriate intervention to be prescribed to prevent GDM in patients with PCOS.; Competing Interests: The authors declare that they have no conflict of interest. (© Georg Thieme Verlag KG Stuttgart · New York.)

Zhao, J. and S. Xiaohui (2022). "Effects of Selenium Supplementation on Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis on Randomized Clinical Trials."
	Review question This study provides a systematic review and meta-analysis of randomized controlled trials, which examined the effect of the selenium supplementation on polycystic ovary syndrome (PCOS). Searches Confirmed studies related to selenium supplementation and PCOS were searched from the databases of EMBASE, PubMed and Web of Science. Data were reported as weighted mean difference (WMD) or standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis was performed with Stata version 12.0. Types of study to be included Randomized controlled clinical trials, case-control studies. Condition or domain being studied POLYCYSTIC OVARY SYNDROME (PCOS) is a common gynecological endocrine disease, which affects 5-20% women of reproductive age worldwide. Its harm is not limited to infertility and abnormal menstruation, but also brings economic burden and long-term health risks to patients. Studies have shown that patients with PCOS often have insulin resistance and abnormal lipid metabolism.In addition, patients with PCOS have oxidative stress. Excessive oxidative stress and depletion of antioxidants may contribute to ovarian mesenchymal hyperplasia. This affects the quality of oocytes in patients with PCOS, and ultimately leads to undesirable pregnancy Participants/population (b) Study population: patients with PCOS and obesity. PCOS was diagnosed on the basis of the revised Rotterdam 2003 criteria [31]. The presence of 2 out of 3 criteria (oligo or/and anovulation, clinical or/and biochemical signs of hyperandro-genism, and polycystic ovary) was recommended as diagnostic of PCOS. (c) Aged 20–40 years Intervention(s), exposure(s) Randomized controlled clinical trials, case-control studies. Patients took selenium or selenium combined with probiotics in the selenium group. Patients took placebo in the control group. Comparator(s)/control Patients took placebo in the control group. Main outcome(s) BMI, Weight, LDL, HDL, In this study, data were analyzed by Stata (version 12.0). P-values were two-sided, and P<0.05 was considered the limit of statistical significance. In addition, the heterogeneity of these seven studies was assessed. In this meta-analysis, I² was used to assess the heterogeneity between these included studies, and I²≥50 was set as significant heterogeneity. For studies with I²≥50%, the random effects model was established for calculation, and for studies with I²＜50%, the fixed effects model was used. The WMD or SMD for continuous variables were used to explain outcomes with the 95% CI. For some data with significant heterogeneity, in-depth research was also conducted on subgroup (or regression) analysis and sensitivity analysis. Additional outcome(s) Not applicable

Zhao, Q. and J. He (2022). "Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials." Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38(7): 558-568.
	Objective: To evaluate the efficacy and safety of using metformin in pregnant women with polycystic ovarian syndrome (PCOS) and to explore the most effective and safe protocol by using a meta-analysis method.; Methods: Medline, EMBASE, Cochrane Library, and other databases were searched for randomized controlled trials and prospective cohort studies enrolling pregnant women with PCOS on receiving metformin or placebo or nothing. Subgroup analyses were undertaken.; Results: A total of 17 studies involving 2899 patients were included. Compared with control group, the use of metformin significantly reduced the incidence of preterm delivery (cumulative rate 3.86% vs 9.19%, relative risk (RR), 0.42 [95% confidence interval (CI), 0.25-0.71,]; p = .001), early miscarriage (cumulative rate 6.58% vs 18.35%, RR, 0.40 [95% CI, 0.20-0.78]; p = .007), gestational diabetes (cumulative rate 12.86% vs 22.91%, RR, 0.48 [95% CI, 0.26-0.89]; p = .02), and pre-eclampsia (cumulative rate 4.95% vs 7.72%, RR, 0.61 [95% CI, 0.40-0.93]; p = .02), the need for insulin treatment throughout pregnancy (cumulative rate 2.14% vs 5.12%, RR, 0.43 [95% CI, 0.22-0.85]; p = .01), and weight gain of pregnant women (mean difference, -2.45, [95% CI, -3.04 to -1.85]; p < .00001).; Conclusions: The use of metformin in pregnant women with PCOS can significantly reduce maternal complications. No significant difference was observed in serious maternal adverse events. The efficacy and safety of metformin are worthy of recognition.

Zhao, Q., et al. (2022). "PCR283 Health-Related Quality of Life in Patients With Advanced or Recurrent Endometrial Cancer Who Have Disease Progression on or Following Prior Treatment With a Platinum-Containing Therapy: Analysis of EQ-5D Utility Scores." Value in Health 25(12 Supplement): S445.
	Objectives: In Study 309/KN-775, treatment with lenvatinib plus pembrolizumab (LEN+PEM) led to significantly longer progression-free and overall survival than treatment of physician's choice (TPC) among patients with advanced endometrial cancer (EC) following prior platinum-based systemic therapy. We present an analysis of patient-reported EQ-5D from Study 309/KN-775. Method(s): Patients were randomized 1:1 to receive LEN 20 mg once daily + PEM 200 mg every 3 weeks (n=411) or TPC (doxorubicin 60 mg/m2 every 3 weeks or paclitaxel 80 mg/m2 weekly for 3 weeks then 1 week off; n=416). EQ-5D-5L was assessed at day 1 of each cycle, at time of discontinuation, and for 4 cycle lengths after discontinuation. EQ-5D-5L responses were converted to UK EQ-5D-3L utility scores. Multivariable linear mixed models were used to estimate the association between EQ-5D and covariates including proximity to death, baseline EQ-5D, and other covariates. Models were selected using the Akaike Information Criterion. Result(s): 7,481 complete EQ-5D observations were available. At baseline (n=731), the mean EQ-5D score was 0.75 (standard deviation 0.20). In the selected model, post-progression status and experiencing adverse events (AEs) were independently associated with small decrements (-0.020; p<0.001 and -0.029; p<0.001, respectively). Increasing proximity to death was associated with worsening EQ-5D (-0.216; p<0.001 for 0-28 days from death), with differences beyond 182 days from death not statistically significant. The direct effect for LEN+PEM vs TPC was not statistically significant, however being on treatment (independent of which treatment) was associated with higher EQ-5D than being off treatment (0.084; p<0.001). Conclusion(s): EQ-5D utility scores have not been reported for this patient population. AEs, disease progression, and time to death were associated with significant deteriorations in quality of life in patients with advanced EC following prior platinum-based systemic therapy. These findings will support future economic evaluations of treatments in advanced EC.Copyright © 2022

Zhao, S., et al. (2024). "Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis." Acta Obstetricia et Gynecologica Scandinavica.
	Introduction: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). Material(s) and Method(s): This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). Result(s): Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) <=28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). Conclusion(s): Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.Copyright © 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Zhao, T.-T., et al. (2023). "Efficacy of high-intensity focused ultrasound combined with LNG-IUS for adenomyosis: a systematic review and meta-analysis." Archives of Gynecology and Obstetrics 308(2): 351-362.
	Objective: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis.; Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I 2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214).; Results: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20).; Conclusions: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution. (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Zhao, X. H. and Z. H. Zhang (2020). "Risk factors for postpartum depression: An evidence-based systematic review of systematic reviews and meta-analyses." Asian Journal of Psychiatry 53: 102353.
	Purpose: Postpartum depression (PPD) is the most common psychiatric condition after childbirth which not only effects the mother's health, but also might have impact on child's development and parenting behaviors. Because the etiology of PPD has not been fully cleared, the efforts towards identification of risk factors are crucial for both the children and mother's health. Method(s): PubMed, EMBASE and PsycINFO databases were searched since inception until July 2019 to collect data about the risk factors of PPD and only systematic review and meta-analysis can be included. Result(s): To identify the real risk factors, protective factors and controversial factors, nineteen parts of the interpretation were adopted. The risk factors are mainly concentrated in the following aspects: violence and abuse, immigration status, gestational diabetes, cesarean section, depressive history, vitamin D deficiency, obese and overweight, postpartum sleep disruption and poor postpartum sleep, lack of social support, traditional dietary pattern (Japanese, Indian, United Kingdom, and Brazilian dietary pattern), multiple births, preterm and low-birth-weight infants, postpartum anemia, negative birth experience. The controversial factors are serum level of cortisol, thyroid peroxidase autoantibodies status, acculturation, traditional confinement practices. Skin-to-skin care, higher concentrations of DHA in mothers' milk, greater seafood consumption, healthy dietary patterns, multivitamin supplementation, fish and PUFA intake, calcium, Vitamin D, zinc and possibly selenium are protective factors. Conclusion(s): Thirteen risk factors were identified, but five factors still controversial due to the insufficient of the evidence. What's more, skin-to-skin care and some nutrition related factors are protective factors against PPD.Copyright © 2020 Elsevier B.V.

Zhao, X.-L., et al. (2021). "Fertility-preserving treatment in patients with early-stage endometrial cancer: A protocol for systematic review and meta-analysis." Medicine 100(48): e27961.
	Background: Endometrial cancer (EC) is the second most common malignancy of the female reproductive system worldwide, and the standard treatment for early-stage EC potentially leads to permanent infertility. The objective of this study was to investigate the efficacies of different methods on fertility preservation in patients with early-stage EC.; Methods: We searched the major online databases (PubMed, Embase, The Cochrane Library, and Web of Science) to collect the research literature on fertility preservation therapy in patients with early-stage well-differentiated EC aged ≤ 40 years from January 1999 to October 2019. The inclusion was performed using the R software (version R3.5.3) meta-analysis of a single rate. The efficacy of the following three fertility preservation treatments was evaluated from four aspects, the complete remission rate (CRR), recurrence rate (ReR), pregnancy rate (PregR), and live birth rate (LBR): a) taking oral progestin only therapy, b) hysteroscopic resection combined with progestin/levonorgestrel-releasing intrauterine system (LNG-IUS)/GnRH-a, c) LNG-IUS or combined with progestin/GnRH-a.; Results: A total of 23 articles were included in this study, including 446 patients with early-stage EC. In the group that took oral progestin only (n = 279), CRR, ReR, PregR, and LBR were 82% (95% confidence interval [CI], 74%-92%, P = .01), 38% (95% CI, 31%-45%, P = .35), 70% (95% CI, 62%-79%, P = .68), and 63% (95% CI, 55%-73%, P = .55), respectively. Hysteroscopic resection combined with progestin/LNG-IUS/GnRH-a therapy group (n = 96) achieved a CRR, ReR, PregR, and LBR of 95% (95% CI, 90%-100%, P = .42), 16% (95% CI, 6%-39%, P = .03), 84% (95% CI, 73%-96%, P = .39), and 72% (95% CI, 59%-87%, P = .28), respectively. LNG-IUS or combined with progestin/GnRH-a therapy group (n = 91) achieved a CRR, ReR, PregR, and LBR of 69% (95% CI, 54%-89%, P < .01), 30% (95% CI, 19%-49%, P = .36), 48% (95% CI, 18%-100%, P < .01), and 36% (95% CI, 10%-100%, P < .01), respectively.; Conclusion: It is safe and effective for young patients with early-stage EC to receive oral progestin, hysteroscopic resection combined with progestin/LNG-IUS/GnRH-a, LNG-IUS, or progestin/GnRH-a.; Inplasy Registration Number: DOI 10.37766/inplasy2020.12.0137.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

zhaosong, w. and x. min (2023). "A meta-analysis of the effect of bilateral salpingectomy on ovarian function during hysterectomy."
	Review question Whether hysterectomy with bilateral salpingectomy has an effect on ovarian function Searches [1 change] The databases retrieved include: PubMed, embase, cochrane, China Biology Medicine disc, CNKI, wangfang data. The search period is from the establishment of the library to 2023-5-16. There is no restriction on the region or language in which the literature is searched. Types of study to be included Cohort studies and case-control studies Condition or domain being studied Whether prophylactic salpingectomy alters the original function of the ovaries and worsens or prematures menopausal symptoms Participants/population Inclusion criteria 1. Not in menopausal and perimenopausal period before surgery, regular menstruation, no perimenopausal symptoms and manifestations. 2. Have benign uterine lesions, such as uterine fibroids, adenomyosis, highgrade squamous intraepithelial lesions of the cervix, endometrial dysplasia or endometrial complex hyperplasia, abnormal uterine bleeding. 3. No history of sex hormone use within 6 months before surgery. 4. No history of malignant tumors, hypertension, diabetes and other endocrine diseases before surgery. 5. No ovarian and fallopian tube lesions before surgery. Exclusion criteria 1 Reviews, reviews, case reports, conference proceedings and repeated publications, literature with incomplete data that cannot be systematically reviewed. 2 Previous malignancy and, endocrine diseases, ovarian insufficiency and history of gynecological surgery. 3 Surgical modalities include open or vaginal hysterectomy, and the surgical scope is subtotal hysterectomy Intervention(s), exposure(s) [1 change] Inclusion Criteria: Patients underwent laparoscopic hysterectomy and bilateral salpingectomy with the same surgical methods, consistent surgical methods, and no major errors. Exclusion criteria: surgical modalities include open or transvaginal surgery, or bilateral tubal removal without removal. Comparator(s)/control [1 change] Inclusion criteria: patients underwent laparoscopic hysterectomy without bilateral salpingectomy. Exclusion criteria: surgical modalities include open or transvaginal surgery. Main outcome(s) The levels of ovarian sex hormones were compared at different times, including preoperative, 1 month after surgery, 3 months after surgery, 6 months after surgery, and 1 year after surgery. The sex hormones compared included estradiol, luteinizing hormone, follicle-stimulating hormone, and anti-Mullerian hormone. Additional outcome(s) None

Zheng, F., et al. (2019). "Protective effect of gonadotropin-releasing hormone agonist against chemotherapy-induced ovarian dysfunction: A meta-analysis." Oncology Letters 17(6): 5319-5326.
	The protective effects of gonadotropin-releasing hormone agonist (GnRHa) against ovarian chemotherapy induced-toxicity have not completely been demonstrated and the impact of chemotherapy on ovarian dysfunction remains unclear. The present meta-analysis aimed to evaluate the efficiency of GnRHa and to determine whether GnRHa could influence the long-term survival rate of patients with cancer. A total of 12 clinical randomized controlled trials were included, consisting of 1,413 patients who were divided into the GnRHa group (n=705) and the control group (n=708). The meta-analysis revealed that GnRHa may significantly improve the menstrual function recovery rate in patients who received chemotherapy [RR=1.29, 95% confidence interval (CI)=1.09-1.54, P=0.004] and reduce the rate of premature ovarian failure (RR=0.47, 95% CI=0.31-0.71, P=0.0004). However, it had no effect on the pregnancy rate (RR=1.40, 95% CI=0.98-1.98, P=0.06), on the rate of disease-free survival and overall survival of patients (disease-free survival rate: RR=1.04, 95% CI=0.95-1.13, P=0.40; overall survival rate: RR=1.02, 95% CI=0.90-1.16, P=0.72). In conclusion, GnRHa may reduce chemotherapy-induced ovarian dysfunction without compromising or influencing the therapeutic effects of chemotherapy.

Zheng, J., et al. (2022). "Effects of Acupuncture Combined with Rehabilitation on Chronic Pelvic Pain Syndrome in Females: A Meta-Analysis Running Head-Acupuncture Combined with Rehabilitation on Chronic Pelvic Pain." Journal of healthcare engineering 2022: 8770510.
	Objective: To investigate the clinical efficacy of this combined treatment for chronic pelvic pain syndrome (CPPS) by meta-analysis.; Methods: Relevant articles were retrieved from PubMed, CNKI, Wanfang Data, Web of Science, and Embase, including randomized controlled trials on acupuncture combined with rehabilitation for CPPS in females.; Results: A total of 224 articles were retrieved in this study, and 14 studies were finally identified for inclusion. Among them, the treatment group was treated with acupuncture combined with pelvic floor rehabilitation therapy, while the control group was treated with acupuncture or pelvic floor rehabilitation therapy. Meta-analysis showed that the treatment effective rate in the treatment group was significantly higher than that in the control group (OR = 6.54; 95% CI: 4.20, 10.21; P < 0.05). After treatment, compared with the control group, the treatment group showed lower incidences of adverse reactions (OR = 0.16; 95% CI: 0.09, 0.27; P < 0.05), bladder prolapse (OR = 0.36; 95% CI: 0.18, 0.73; P < 0.05), cervical prolapse (OR = 0.22; 95% CI: 0.10, 0.49; P < 0.05), and pelvic peritoneal hernia (OR = 0.14; 95% CI: 0.05, 0.38; P < 0.05); in addition, the treatment group was also associated with lower pain score (SMD = -4.05; 95% CI: -6.75, -1.34; P < 0.05) and pelvic dysfunction score (SMD = -4.35; 95% CI: -5.37, -3.34; P < 0.05).; Conclusion: Acupuncture combined with rehabilitation is effective for CPPS in females, which can significantly reduce the pain intensity and improve pelvic dysfunction of patients.; Competing Interests: The authors declare that they have no conflicts of interest. (Copyright © 2022 Jie Zheng et al.)

Zheng, L., et al. (2023). "[Analysis of regularity of acupoint selection and compatibility of acupuncture in the treatment of postpartum depression]." Zhen ci yan jiu = Acupuncture research 48(3): 305-310.
	Objective: To analyze the regularity of acupoint selection, and compatibility of acupuncture in the treatment of postpartum depression.; Methods: Articles both in English and Chinese published in databases of CNKI, Wanfang, VIP, Chinese biomedical literature database (SinoMed), PubMed, Embase, Cochrane Library from the inception to February of 2021 were retrieved by using key words "acupuncture" or "moxibustion" or "electroacupuncture" or "acupoint application" or " acupoint burying" or "acupoint injection" or "fire needling" and "postpartum depression" or "puerperal depression". The frequencies of selected acupoints and meridians were counted by using data mining technology, and the points with high frequency were analyzed by cluster analysis.; Results: A total of 42 articles were included, containing 65 prescriptions and 80 points. The highest frequency of acupoints were Baihui (GV20), Sanyinjiao (SP6), Taichong (LR3), Neiguan (PC6), Zusanli (ST36) and Shenmen (HT7). The most frequently selected channels were Bladder Meridian, Governor Meridian and Liver Meridian. Among the specific points, intersection points, five- shu points, yuan-source points and back- shu points were widely used. Through cluster analysis, four effective cluster groups ［GV20-SP6, LR3-PC6, Xinshu (BL15)-Ganshu (BL18)-Pishu (BL20)-Guanyuan (CV4), Hegu (LI4)-Qihai(CV6)-Qimen (LR14)］ were obtained, as well as a group of main points (GV20-SP6-LR3-PC6-ST36-HT7) and two groups of matching points ［LI4-CV6-LR14 and BL15-BL18-BL20-CV4-Sishencong (EX-HN1)］.; Conclusion: Through data mining technology, this paper summarized the acupoint selection and compatibility law of acupuncture in the treatment of postpartum depression, focusing on regulating Qi, blood and spirit, so as to provide reference for guiding the clinical acupuncture treatment and scientific research of postpartum depression.

Zheng, L., et al. (2023). "Acupuncture-adjuvant therapies for treating perimenopausal depression: A network meta-analysis." Medicine 102(33): e34694.
	Background: The issues related to the treatment of perimenopausal depression (PMD) are the side effects of antidepressants and hormone replacement therapy. The aim of this study was to assess the efficiency and safety of acupuncture and moxibustion in PMD patients.; Methods: Databases, namely PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, CBM, VIP, and WanFang, were reviewed for related randomized controlled trials dated between database inception and November 22, 2022. The primary outcomes were the efficacy rate and the Hamilton Depression Scale score. The secondary outcomes were the levels of follicle-stimulating hormone, luteinizing hormone, and estradiol and the Kupperman score. Odds ratios (ORs) were generated as the effect size for dichotomous outcomes, while the standard mean difference (SMD) ± standard deviation was used for continuous outcomes. Matrices were developed to demonstrate pairwise comparisons of regimens related to each endpoint. Utilizing Review Manager (RevMan) 5.3, Stata 16.0 and SPSS 21, data were analyzed.; Results: In total, 27 studies involving 2269 PMD patients and 8 therapeutic measures were incorporated into the network meta-analysis (NMA). The NMA showed that warm acupuncture (OR = 1.55, 95% CI: 1.00-2.44), electroacupuncture (OR = 1.34, 95% CI: 1.00-1.8), abdominal acupuncture (OR = 1.19, 95% CI: 0.73-1.96), and common acupuncture (OR = 1.4, 95% CI: 0.9-2.17) were more effective than fluoxetine + menopausal hormone treatment in the treatment of PMD. The NMA also showed that, based on the Hamilton Depression Scale score, warm acupuncture was more effective than the other 4 acupuncture-related treatments, i.e., electroacupuncture (SMD = -1.22, 95% CI: -2.34 to -0.09), thread embedding (SMD = -1.31, 95% CI: -2.21 to -0.40), abdominal acupuncture (SMD = -1.33, 95% CI: -2.42 to -0.24), and common acupuncture (SMD = -1.46, 95% CI: -2.26 to -0.66). The cumulative ranking probability (SUCRA) showed that warm acupuncture (99.6%) was the best treatment method.; Conclusions: The findings of this network meta-analysis may help patients and therapists choose the best acupuncture therapy for treating perimenopausal depression patients and furnish reliable evidence for guidelines.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zheng, S., et al. (2023). "Effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer: A meta-analysis." International wound journal 20(4): 1061-1071.
	We performed a meta-analysis to evaluate the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer. A systematic literature search up to July 2022 was performed and 10 231 subjects with cervical cancer at the baseline of the studies; 4307 of them were using the minimally invasive surgery, and 5924 were using laparotomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer using the dichotomous methods with a random or fixed-effect model. The minimally invasive surgery had significantly lower wound infection (OR, 0.20; 95% CI, 0.13-0.30, P < .001), and postoperative complications (OR, 0.48; 95% CI, 0.37-0.64, P < .001) in subjects with cervical cancer compared laparotomy. However, minimally invasive surgery compared with laparotomy in subjects with cervical cancer had no significant difference in intraoperative complications (OR, 1.04; 95% CI, 0.80-1.36, P = 0.76). The minimally invasive surgery had significantly lower wound infection, and postoperative complications however, had no significant difference in intraoperative complications in subjects with cervical cancer compared with laparotomy. The analysis of outcomes should be with caution because of the low sample size of 22 out of 41 studies in the meta-analysis and a low number of studies in certain comparisons. (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Zheng, S., et al. (2022). "Role of magnetic resonance-high intensity focused ultrasound (MR-HIFU) in uterine fibroids management: an updated systematic review and meta-analysis." Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques 17(1): 83-94.
	Introduction: Magnetic resonance-high intensity focused ultrasound (MR-HIFU) has revolutionized the treatment of Uterine fibroids. Usually, they are associated with prolonged heavy bleeding during the menstrual period, sacral pain, and increased frequency of UTIs, secondary dysmenorrhea, constipation, and pregnancy-associated problems. It also impacts usual activities, which lead to diminished quality of life and rising healthcare costs. Generally, surgery is the only choice for uterine fibroids; however, MR-HIFU is an entirely non-invasive novel therapy, preferred in pregnancy desiring females.; Aim: To re-evaluate the efficacy of magnetic resonance-high intensity focused ultrasound (MRHIFU) therapy for uterine fibroids.; Material and Methods: Randomized clinical trials (RCTs), prospective or retrospective non-randomized, and cross-over studies that considered clinically symptomatic uterine fibroid treatment were included. Meta-analysis was performed using NCSS software, and data were analyzed at a 95% confidence level with a significance level of 0.05. In addition, the non-perfused volume percentage (NPV%), transformed Symptom Severity Score percentage change (tSSS change%), and health-related quality of life (HR-QoL) were computed.; Results: The overall effect of NPV% was 67.60%, where the 95% confidence interval ranged from 55.58% to 79.62%. The overall impact of tSSS% change was approximately 50% (0.54) with 95% CI of 0.41-0.66 of 3 months, 6 months, and 12 months in the included studies. There was a significant improvement in the health-related quality of life (HR-QoL).; Conclusions: The efficacy of MR-HIFU therapy was improved as treatment protocols aimed for total ablation.; Competing Interests: The authors declare no conflict of interest. (Copyright: © 2021 Fundacja Videochirurgii.)

Zheng, W., et al. (2023). "Meta-Analysis of Shenqi Fuzheng Injection as an Adjuvant Therapy for the Treatment of Cervical Cancer." Journal of Biological Regulators and Homeostatic Agents 37(3): 1629-1639.
	Background: The present study aimed to systemically evaluate the safety and clinical efficacy of Shenqi Fuzheng injection (SFI) combined with conventional treatment for cervical cancer. Method(s): Studies investigating the effect of SFI plus conventional treatment versus conventional treatment until 19 April 2021, were systematically reviewed. RevMan 5.3 software (The Nordic Cochrane Centre, Copenhagen, Denmark) was utilized for the present data analysis. Result(s): Eight articles were included in this study. Patients in the SFI group had better complete remission (CR) [risk ratio (RR) 95% confidence interval (95% CI) = 1.69 (1.02, 2.82), p = 0.04], partial remission (PR) [RR (95% CI) = 1.78 (1.21, 2.64), p = 0.004], objective response rate (ORR) [RR (95% CI) = 1.76 (1.36, 2.30), p < 0.0001], improved quality of life (RR (95% CI) = 1.80 (1.30, 2.49), p = 0.0004), improved plus stable quality of life (RR (95% CI) = 1.27 (1.10, 1.46), p = 0.001), more CD3+ T cell [weighted mean difference (WMD) (95% CI) = 9.76 (5.79, 13.73), p < 0.00001], CD4+ T cell (WMD (95% CI) = 8.16 (6.36, 9.95), p < 0.00001), NK (natural killer) cell (WMD (95% CI) = 3.16 (0.02, 6.31), p = 0.05), higher CD4/CD8 (WMD (95% CI) = 0.64 (0.23, 1.05), p = 0.002), less CD8+ T cell (WMD (95% CI) = -5.66 (-8.18, -3.13), p < 0.0001), and less risk of leukopenia (RR (95% CI) = 0.52 (0.38, 0.69), p < 0.00001) and nausea or vomiting (RR (95% CI) = 0.59 (0.45, 0.77), p = 0.0001). Conclusion(s): SFI combined with conventional treatment exhibited better therapeutic efficacy and safety than those of conventional chemotherapy.Copyright © 2023 The Author(s).

Zheng, X., et al. (2022). "Effects of Chinese Herbal Medicine on ovarian functions in the patients with endometriosis: A systematic review and meta-analysis of randomized controlled trials." European journal of integrative medicine 51: 102125.
	Introduction: When using Chinese Herbal Medicine (CHM) to treat endometriosis, the effects of CHM on the ovarian function have received little attention. This systematic review and meta-analysis aimed to evaluate the effects and safety of CHM on the ovarian function in patients with endometriosis. Method(s): Eight electronic databases were searched from their inception to March 2, 2021. We compared those receiving CHM with controls, all studies included were randomized controlled trials (RCTs). Statistical analysis was performed using standard mean difference of hormonal levels: Estradiol(E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH). Subgroup analysis and sensitivity analysis were conducted. Result(s): A total of 844 patients from 11 RCTs were included. In E2 levels, the analysis revealed a significant effect in favor of CHM group comparedwith the control group (SMD = 3.05, 95%CI = 0.29 to 1.32, P = 0.002). After subgroup analyses, there were still significant effects in both non-operative subgroup (SMD = 2.04, 95%CI = 0.04 to 1.88, P = 0.04) and post-operative subgroup (SMD = 2.19, 95%CI = 0.08 to 1.42, P = 0.03). There were no significant differences between the two subgroups in both FSH levels (P > 0.05) and LH levels (P > 0.05), and the subgroup analyses showed similar results. No adverse events were reported. Conclusion(s): CHM may improve ovarian function in patients with endometriosis through increasing E2 levels whether there is surgery or not, which may indicate a referable and safe treatment of endometriosis. Due to the weak evidence, high-quality clinical trials are needed to support this conclusion. (PROSPERO ID is CRD42021240162)Copyright © 2022

Zheyun, X., et al. (2022). "Efficacy of Different Growth Hormone Supplementation Protocols for Women with Poor Ovarian Response undergoing IVF/ICSI: a Systematic Review and Meta-analysis."
	
Zhong, D., et al. (2019). "Efficacy and safety of acupuncture therapy for urinary incontinence in women: A systematic review and meta-analysis." Medicine (United States) 98(40): e17320.
	Background:Urinary incontinence (UI), affects women more frequently than men, with a prevalence to 30-40% of perimenopausal women and almost 50% among women aged over 70 years. caused severe psychological burden and bringing negatively impact to the quality of life, increased caregiver burden and economic cost. Acupuncture is often used to treat them. We aim to conduct a systematic review to evaluate the efficacy of acupuncture for women experiencing UI. Method(s):The following electronic databases will be searched from inception to Jan. 2020: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Traditional Chinese Medicine, Chinese Biomedical Literature Database (CBM), Wan-Fang Database and Chinese Scientific Journal Database (VIP database).All published randomized controlled trials in English or Chinese related to acupuncture for urinary incontinence in women will be included. The primary outcome will be the change from baseline in the amount of urine leakage measured by the 1-hour pad test. Adverse events will be the secondary outcome. Study selection, data extraction, and assessment of study quality will be performed independently by two reviewers. RevMan V.5.3.5 software will be used for the assessment of risk of bias and data synthesis. Result(s):This study will provide a high-quality synthesis of current evidence of acupuncture for UI from the 1-hour pad test. Conclusion(s):The conclusion of our study will provide an evidence to judge whether acupuncture is an effective intervention for patients suffered from UI.PROSPERO registration number:CRD42019133195.Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

Zhong, Y., et al. (2022). "Use of Machine Learning to Estimate the Per-Protocol Effect of Low-Dose Aspirin on Pregnancy Outcomes: A Secondary Analysis of a Randomized Clinical Trial." JAMA Network Open 5(3): e2143414.
	Importance: In randomized clinical trials (RCTs), per-protocol effects may be of interest in the presence of nonadherence with the randomized treatment protocol. Using machine learning in per-protocol effect estimation can help avoid model misspecification owing to strong parametric assumptions, as is common with standard methods (eg, logistic regression).; Objectives: To demonstrate the use of ensemble machine learning with augmented inverse probability weighting (AIPW) for per-protocol effect estimation in RCTs and to evaluate the per-protocol effect size of aspirin on pregnancy.; Design, Setting, and Participants: This secondary analysis used data from 1227 women in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a multicenter, block-randomized, double-blind, placebo-controlled clinical trial of the effect of daily low-dose aspirin on pregnancy outcomes in women at high risk of pregnancy loss. Participants were recruited at 4 university medical centers in the US from June 15, 2007, to July 15, 2012. Women were followed up for 6 menstrual cycles for attempted pregnancy and 36 weeks of gestation if pregnancy occurred. Follow-up was completed on August 17, 2012. Data analyses were performed on July 9, 2021.; Exposures: Daily low-dose (81 mg) aspirin taken at least 5 of 7 days per week for at least 80% of follow-up time relative to placebo.; Main Outcomes and Measures: Pregnancy detected using human chorionic gonadotropin (hCG) levels.; Results: Among the 1227 women included in the analysis (mean SD age, 28.74 [4.80] years), 1161 (94.6%) were non-Hispanic White and 858 (69.9%) adhered to the protocol. Five machine learning models were combined into 1 meta-algorithm, which was used to construct an AIPW estimator for the per-protocol effect. Compared with adhering to placebo, adherence to the daily low-dose aspirin protocol for at least 5 of 7 days per week was associated with an increase in the probability of hCG-detected pregnancy of 8.0 (95% CI, 2.5-13.6) more hCG-detected pregnancies per 100 women in the sample, which is substantially larger than the estimated intention-to-treat estimate of 4.3 (95% CI, -1.1 to 9.6) more hCG-detected pregnancies per 100 women in the sample.; Conclusions and Relevance: These findings suggest that a low-dose aspirin protocol is associated with increased hCG-detected pregnancy in women who adhere to treatment for at least 5 days per week. With the presence of nonadherence, per-protocol treatment effect estimates differ from intention-to-treat estimates in the EAGeR trial. The results of this secondary analysis of clinical trial data suggest that machine learning could be used to estimate per-protocol effects by adjusting for confounders related to nonadherence in a more flexible way than traditional regressions.; Trial Registration: ClinicalTrials.gov Identifier: NCT00467363.

Zhong, Y., et al. (2020). "Effectiveness of electroacupuncture for female stress urinary incontinence: a systematic review and Meta-analysis." Journal of Traditional Chinese Medicine 40(5): 707-720.
	OBJECTIVE: To evaluate the effectiveness of electroacupuncture (EA) for female stress urinary incontinence (SUI). METHOD(S): We searched 12 databases electronically from inception to November 2018 without language restrictions. We included randomized controlled trials (RCTs) involving women with SUI, but excluded other types of urinary incontinence or studies that were not RCTs. Two independent reviewers extracted study characteristics, with disagreements resolved by consensus. Data were pooled and expressed as mean difference (MD) for continuous outcomes and relative risk (RR) for dichotomous outcomes, with 95% confidence intervals (CI). This study was registered with the International Prospective Register of Systematic Reviews (number CRD42018089734). RESULT(S): We found very low to high level evidence that EA improved the effective rate (RR = 2.03, 95% CI: 1.40, 2.95; P = 0.0002) and reduced urine leakage as measured by the 1-hour pad test (MD = 3.33, 95%CI: 0.89, 5.77; P = 0.008), International Consultation on Incontinence Questionnaire Short Form score (MD = 3.14, 95% CI: 2.42, 3.85; P < 0.00001), and 72-hour incontinence episodes (MD = 1.17, 95%CI: 0.56, 1.78; P = 0.0002) compared with sham electroacupuncture (SA), pelvic floor muscle training, and medication. CONCLUSION(S): The effectiveness and safety of EA for key outcomes for women with SUI are statistically significantly better than those of SA, but most available evidence is very low or low quality. More well-designed RCTs are needed to confirm these findings.Copyright © 2020 JTCM. All rights reserved.

Zhong, Y., et al. (2019). "Acupuncture in improving endometrial receptivity: a systematic review and meta-analysis." BMC Complementary and Alternative Medicine 19(1): 61.
	Background: This systematic review aimed at summarizing and evaluating the evidence of randomized controlled trials (RCTs) using acupuncture to improve endometrial receptivity (ER).; Methods: We searched 12 databases electronically through August 2018 without language restrictions. We included RCTs of women of infertility due to low ER, and excluded infertility caused by other reasons or non-RCTs. Two independent reviewers extracted the characteristics of studies and resolved the differences through consensus. Data were pooled and expressed as standard mean difference (SMD) or mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes, with 95% confidence interval (CI).; Results: We found very low to moderate level of evidence that acupuncture may improve pregnancy rate (RR = 1.23 95%CI[1.13, 1.34] P < 0.00001) and embryo transfer rate (RR = 2.04 95%CI[1.13, 3.70] P = 0.02), increase trilinear endometrium (RR = 1.47 95%CI [1.27, 1.70] P < 0.00001), thicken endometrium (SMD = 0.41 95% CI [0.11, 0.72] P = 0.008), reduce resistive index (RI) (MD = -0.08 95% CI [- 0.15, - 0.02] P = 0.01), pulse index (PI) (SMD = -2.39 95% CI [- 3.85, - 0.93] P = 0.001) and peak systolic velocity/ end-diastolic blood velocity (S/D) (SMD = -0.60 95% CI [- 0.89, - 0.30] P < 0.0001), compared with medication, sham acupuncture or physiotherapy. Acupuncture was statistically significant as a treatment approach.; Conclusion: The efficacy and safety of acupuncture on key outcomes in women with low ER is statistically significant, but the level of most evidence was very low or low. More large-scale, long-term RCTs with rigorous methodologies are needed.

Zhou, C., et al. (2022). "Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers." ESMO Open 7(2): 100417.
	Background: Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment.; Patients and Methods: Patients (n = 124) with advanced biliary tract cancer (ABC) received cisplatin/gemcitabine with cediranib or placebo (ABC-03 trial). Concentrations of pTie2 were measured longitudinally from before treatment until disease progression. Data from patients with ovarian cancer (n = 92, ICON7 trial) and patients with colorectal cancer (CRC) (n = 70, Travastin trial) were also included.; Results: Cediranib-treated ABC patients were deconvoluted into distinct groups where in one group pTie2 trajectories resembled those seen in placebo-treated patients and in another pTie2 significantly reduced (t-test P = 2.7 × 10 -14 ). Using the 95% confidence interval for these two groups, we defined a vascular complete response (vCR) as a 24% reduction in pTie2 within 9 weeks; vascular no response (vNR) as a 7% increase in pTie2, and a vascular partial response (between these limits). vCR cediranib-treated patients had significantly improved progression-free survival (8.8 versus 7.5 months, restricted mean ratio 0.73, P = 0.012) and overall survival (18.8 versus 12.1 months, hazard ratio 0.49, P = 0.02). By integrating data across ovarian cancer, CRC and ABC, we show that (i) patients with vNR do not benefit from VEGFi and (ii) Tie2-defined vascular progression occurs sufficiently in advance of radiological progressive disease that changes in treatment could be offered to prevent clinical deterioration.; Conclusion: pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.; Competing Interests: Disclosure JWV reports personal fees from Agios, AstraZeneca, Baxter, Genoscience Pharma, Hutchison Medipharma, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Mundipharma EDO, Mylan, QED, Servier, Sirtex and Zymerworks; and grants, personal fees and non-financial support from NuCana, outside the submitted work. GCJ reports research funding from AstraZeneca for clinical trials outside of the submitted work. Research funding has been received from: AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Epigene Therapeutics Inc, Angle PLC, Menarini, Clearbridge Biomedics, Thermo Fisher Scientific and Neomed Therapeutics. CD has received honoraria for consultancy/advisory boards from Biocartis, Merck and AstraZeneca. All other authors have declared no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Zhou, G., et al. (2021). "Glucocorticoid supplementation improves reproductive outcomes in infertile women with antithyroid autoimmunity undergoing ART: A meta-analysis." Medicine 100(16): e25554.
	Background: Thyroid autoimmune disease (TAI) has been verified to be related to multiple adverse pregnancy outcomes. A growing number of evidences highlight the protective roles of glucocorticoid on the treatments of TAI. This meta-analysis aimed to study whether it is beneficial to add glucocorticoid treatment in infertile women with TAI when they are undergoing assisted reproductive technology (ART).; Methods: We conducted a systematic search in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu China Science and Technology Journal Databases (VIP database) up to September 10, 2020. The Revman 5.3 software was utilized for data statistics. We used a random-effects model to analyze data and the odds ratio (OR) combining with 95% confidence interval (95% CI) were employed to reveal the results.; Results: Three publications with 237 antithyroid antibody (ATA)-positive and 384 ATA-negative women were included in the final analysis. Overall, glucocorticoid therapy showed satisfying effects on improving clinical pregnancy rate (OR = 4.63, 95% CI [2.23, 9.58], I2 = 0.0%, P < .0001) and live birth rate (OR = 3.19, 95% CI [1.13, 9.04], I2 = 0.0%, P = .03) of ATA-positive women compared with control group. However, it seems that glucocorticoid showed no significant difference in the abortion rate (OR = 0.62, 95% CI [0.09, 4.32], I2 = 35%, P = .64) and oocyte recovery (OR = 2.26, 95% CI [-1.46, 5.99], I2 = 79%, P < .0001) between the 2 groups.; Conclusions: Glucocorticoid may improve the pregnancy outcomes of ART women with ATA positive, but there is no significant reduction in the risk of miscarriage. Due to the limited enrolled references, glucocorticoid adjuvant therapy should be applied after more randomized controlled trials.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zhou, H., et al. (2022). "A Potential Mechanism of Kidney-Tonifying Herbs Treating Unexplained Recurrent Spontaneous Abortion: Clinical Evidence From the Homogeneity of Embryo Implantation and Tumor Invasion." Frontiers in Pharmacology 12: 775245.
	Background: Kidney-tonifying herbs (KTHs) are widely used to treat unexplained recurrent spontaneous abortion (URSA) based on the theory of traditional Chinese medicine (TCM). However, there is still a lack of systematic evaluation and mechanistic explanation for these treatments. Objective: The purpose of this study was to assess the clinical efficacy, and to investigate the potential mechanisms, of KTH based on TCM for the treatment of URSA. Methods: A systematic literature search was conducted within PubMed, Embase, China Biomedical Literature database, Web of Science (WOS), China National Knowledge Infrastructure (CNKI) database, and the Wanfang database to find articles reporting on the Chinese herbal formula based around KTH for treating URSA, which were published between January 2010 and June 2021. A full bibliometric analysis was carried out; in addition, randomized controlled trial (RCT) articles were selected for systematic evaluation and meta-analysis. The drugs with the highest frequency of KTHs were screened for meta-analysis. Finally, network analysis and molecular docking were used to study the key components and potential pathway of KTHs in the treatment of URSA. Results: The meta-analysis included nine RCTs involving 1,054 subjects. Compared with the control groups, the clinical efficacy of TCM-based KTHs in the treatment of URSA patients significantly improved outcomes. Additionally, a component target pathway network was identified, which included 32 potential blood activating components and 113 main targets. Japonine, sopranol, lysine, and matrine were considered the most important bioactive molecules for KTHs. The key potential therapeutic pathway for URSA was a tumor-related signaling pathway. The target genes for URSA regulated by KTHs were highly similar to tumor biological processes such as the regulation of apoptotic signaling pathways, inflammatory responses, angiogenesis, and epithelial metabolic transition. Conclusion: KTH has great potential for treating URSA. Because the maintenance of pregnancy has a high similarity with tumor invasion, the research relating to tumor mechanisms should also be followed up as it may lead to new ideas and breakthroughs for research into URSA. At the same time, embryonic and decidual cells share a high degree of cellular heterogeneity and spatial structural complexity with tumor cells, and a single cell combined with spatial omics may be the best future approach for validating KTH mechanisms.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Zhou, Yang, Deng, Yao and Liao.)

Zhou, J., et al. (2023). "Effects of Ranvartinib on Hypoxia Inducible Factor 2, E2F Transcription Factor 1 and Vaginal Micro ecology in Patients with Gynecological Tumors." Revista de Psiquiatria Clinica 50(3): 189-194.
	Objective: To investigate the effect of ranvartinib on the transcription of hypoxia inducible factor 2 (HIF-2) and E2F in patients with gynecologic tumors factor 1 (E2F-1) and vaginal micro ecology. Method(s): 96 patients with endometrial cancer who visited our hospital from January 2020 to January 2022 were selected. They were divided into the combination group (56 cases) and the single drug group (40 cases) according to whether they were treated with ranvartinib or not. All patients were treated with surgery first, and all patients were given cindilimab after surgery. All patients in the combination group were treated with ranvartinib after surgery. The follow-up period was 3 to 9 months. Finally, 2 patients in the two groups were lost to follow-up, including 6 patients died of endometrial cancer. Serum HIF-2 levels were detected before and after treatment in the two groups of patients, and E2F-1 positive cell count score, vaginal micro ecology (Nugent score, Donders score), efficacy (the main observation index was progression free survival (PFS), and the secondary observation index was objective response rate (ORR) and disease control rate (DCR)) and safety were evaluated. Result(s): After treatment, the scores of HIF-2 and E2F-1 positive cells, Nugent score and Donders score in the two groups were significantly lower than those before operation (P<0.05), and the above indexes in the combined group were significantly lower than those in the single drug group (P<0.05); The median PFS of the combination group was 119 (69.22 163.24) days, and that of the single drug group was 74 (46.27 99.17) days. There was a statistical difference in PFS between the two groups (log rank=6.893, P=0.009). ORR and DCR of the combination group were significantly h igher than those of the single drug group (P<0.05); The incidence of fatigue, appetite loss, hypertension, and diarrhea were significantly lower than that in the single-agent group (P <0.05). Conclusion(s): Compared with the single use of cindilimab, the combination of ranvartinib can effectively reduce the HIF-2 level and E2F-1 positive cell number score, Nugent score, and Donders score, which has a good effect in preventing the continuous deterioration of endometrial cancer, weakening tumor invasion, and improving the vaginal micro biotic imbalance of patients, with slight adverse reactions.Copyright © 2023, Universidade de Sao Paulo. Museu de Zoologia. All rights reserved.

Zhou, J., et al. (2023). "Urinary retention between nerve-sparing radical hysterectomy and radical hysterectomy for cervical cancer: A meta-analysis." Medicine 102(9): e32985.
	This study intended to assess the urinary retention between nerve-sparing radical hysterectomy and radical hysterectomy in cervical cancer. Relevant studies were selected from databases of PubMed, Embase, Wanfang, and China National Knowledge Internet with the last report up to January 15, 2022. Hazard ratio (HR) and 95% confidence interval (CI) were chosen as the evaluation index. Heterogeneity was assessed using Cochran Q test and I2 test. Subgroup analysis was conducted based on areas and cancer types (primary and metastatic cancer). A total of 8 articles (retrospective cohort studies) were selected in the meta-analysis. There were significant correlations between nerve-sparing radical hysterectomy and radical hysterectomy in related with urinary retention (HR [95% CI] = 1.78 [1.37, 2.31], P < .001) and (HR [95% CI] = 2.49 [1.43, 4.33], P = .001) of cervical cancer patients. Egger test revealed a significant publication bias (P = .014). Sensitivity analysis via omitting 1 study at each time showed that omission of any study made significant difference (P < .05), indicating reliability and good stability for the analysis. Additionally, there were significant heterogeneities in most subgroups.; Competing Interests: I have no commercial associations (e.g., consultancies, stock ownership, equity interests, patent-licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zhou, K., et al. (2021). "Chinese herbal medicine for subfertile women with polycystic ovarian syndrome." The Cochrane Database of Systematic Reviews 6: CD007535.
	Background: Polycystic ovarian syndrome (PCOS) is characterised by both metabolic and reproductive disorders, and affects 5% to 15% of women of reproductive age. Different western medicines have been proposed for PCOS-related subfertility, such as oral contraceptives, insulin sensitisers and laparoscopic ovarian drilling (LOD). Chinese herbal medicines (CHM) have also been used for subfertility caused by PCOS for decades, and are expected to become an alternative treatment for subfertile women with PCOS.; Objectives: To assess the efficacy and safety of Chinese herbal medicine (CHM) for subfertile women with polycystic ovarian syndrome (PCOS).; Search Methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and six other databases, from inception to 2 June 2020. In addition, we searched three trials registries, the reference lists of included trials and contacted experts in the field to locate trials.; Selection Criteria: We included randomised controlled trials (RCTs) comparing CHM versus placebo, no treatment or conventional (western) therapies for the treatment of subfertile women with PCOS.; Data Collection and Analysis: Two review authors independently screened trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods.; Main Results: We included eight RCTs with 609 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (EE/CPA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall certainty of the evidence for most comparisons was very low. None of the included studies reported the primary outcome, live birth rate. Most studies reported the secondary outcomes, and only one study reported data on adverse events. In trials that compared CHM to clomiphene (with or without LOD in both study arms), we are uncertain of the effect of CHM on pregnancy rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.63 to 3.19; I 2 = 28%; 3 studies, 140 participants; very low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 21.5%, the chance following CHM would vary between 14.7% and 46.7%. No study reported data on adverse events. When CHM plus clomiphene was compared to clomiphene (with or without EE/CPA), there was low certainty evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 3.06, 95% CI 2.05 to 4.55; I 2 = 10%; 6 studies, 470 participants; low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 31.5%, the chance following CHM plus clomiphene would vary between 48.5% and 67.7%. No data were reported on adverse events. In trials that compared CHM plus follicle aspiration and ovulation induction to follicle aspiration and ovulation induction alone, we are uncertain of the effect of CHM on pregnancy rates (OR 1.62, 95% CI 0.46 to 5.68; 1 study, 44 women; very low certainty evidence). Results suggest that if the chance of pregnancy following follicle aspiration and ovulation induction is assumed to be 29.2%, the chance following CHM with follicle aspiration and ovulation induction would vary between 15.9% and 70%. Reported adverse events included severe luteinised unruptured follicle syndrome (LUFS) (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence), ovarian hyperstimulation syndrome (OHSS) (Peto OR 0.16, 95% CI 0.00 to 8.19; 1 study, 44 women; very low certainty evidence) or multiple pregnan y (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence). These results suggest that if the chances of LUFS, OHSS, and multiple pregnancy following follicle aspiration and ovulation induction are assumed to be 8.3%, 4.2%, and 8.3% respectively, the chances following CHM with follicle aspiration and ovulation induction would be 0.5% to 35.8%, 0% to 26.3% and 0.5% to 35.8% respectively. In trials that compared CHM plus LOD to LOD alone, we are uncertain if CHM improves pregnancy rates (OR 3.50, 95% CI 0.72 to 17.09; 1 study, 30 women; very low certainty evidence). Results suggest that if the chance of pregnancy following LOD is assumed to be 40%, the chance following CHM with LOD would vary between 32.4% and 91.9%. No data were reported on adverse events. We are uncertain of the results in the comparison groups for all outcomes. The certainty of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs.; Authors' Conclusions: There is insufficient evidence to support the use of CHM for subfertile women with PCOS. No data are available on live birth. We are uncertain of the effect of CHM on pregnancy rates for there is no consistent evidence to indicate that CHM influences fertility outcomes. However, we find that the addition of CHM to clomiphene may improve pregnancy rates, but there is very limited, low certainty evidence for this outcome. Furthermore, there is insufficient evidence on adverse effects to indicate whether CHM is safe. In the future, well-designed, carefully conducted RCTs are needed, with a particular focus on the live birth rate and other safety indexes. (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Zhou, L., et al. (2023). "The efficiency of ultrasound-guided erector spinae plane block in early cervical cancer patients undergoing laparotomic radical hysterectomy: A double-blind randomized controlled trial." Frontiers in surgery 9: 1039629.
	Aims: We aim to compare the efficiency of erector spinae plane block (ESPB) with transversus abdominis plane block (TAPB) in patients undergoing laparotomic radical hysterectomy because only a few studies are reported exploring this matter.; Methods: In this randomized controlled trail, 154 eligible patients were randomly allocated into ESPB group [ESPB + patient-controlled intravenous analgesia (PCIA)] and TAPB group (TAPB + PCIA) at 1:1 ratio. The primary outcome was visual analog scale (VAS) score at rest state at 12 h.; Results: We found that ESPB group was associated with the lower VAS scores at rest and cough state than TAPB group at 2, 4, 6, 12, and 24 h postoperatively ( P < 0.05). Less analgesic consumption and sufentanil consumption in PCIA pump were found in the ESPB group ( P < 0.05). Moreover, ESPB group was followed by fewer rescue analgesia requirements, less rescue analgesic consumption, less adverse reactions, and higher analgesia satisfaction ( P < 0.05).; Conclusions: Our study found that ESPB had advantages on analgesic effect and opioids consumption. In the future, more studies were needed to confirm our findings. Systematic Review Registration: https://www.chictr.org.cn/index.aspx, identifier: ChiCTR2100044240.; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Zhou, Wang, Liu, Yan, Song, Shu, Wang and Wei.)

Zhou, P., et al. (2021). "Pelvic bone marrow sparing radiotherapy for cervical cancer: A systematic review and meta-analysis." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 165: 103-118.
	Backgrounds: Concurrent chemo-radiotherapy in patients with locally advanced cervical cancer has significant hematologic toxicities (HT), leading to treatment disruption and affecting patient prognosis. We performed the meta-analysis to assess the clinical benefit of pelvic (active) bone marrow (BM) sparing radiotherapy.; Methods: A systematic methodological search of six primary electronic databases was performed. This systematic review mainly assessed the differences in pelvic (active) BM dose-volume parameters (DVP), hematologic toxicity of pelvic (active) BM sparing versus non-sparing radiotherapy plans. The secondary objective was to explore optimal dose limitation regimens and evaluate other radiation-induced toxicities (gastrointestinal and urological toxicity (GT/UT)). Random-effects models were used for meta-analysis.; Results: Final 65 publications that met inclusion criteria were included in the meta-analysis and descriptive tables. Meta-analysis of mean pelvic BM-DVP differences showed that pelvic BM-V 10,20,40,50 (Vx: volume of BM receiving ≥ X Gy) were reduced by -4.6% [95% CI: -6.6, -2.6], -10.9% [-13.2, -8.6], -7.3% [-9.5, -5.2] and -3.4% [-4.3, -2.4] in pelvic BM-sparing plans. Pelvic BM sparing radiotherapy decreased G2/3+ HT [odds ratio (OR) 0.31, (0.23, 0.41)/0.42, (0.28, 0.63)], without increasing GT [G2/3+: OR 0.76, (0.51, 1.14)/0.90, (0.47, 1.74)] and UT [G2/3+: OR 0.91, (0.57, 1.46)/0.54, (0.25, 1.17)]. Pelvic active BM sparing radiotherapy also reduced HT [G2/3+ HT: OR 0.42, (0.23, 0.77)/0.34, (0.16, 0.72)]. There were significant variations between publications in dose restriction regimens.; Conclusion: The pelvic BM protection radiotherapy can decrease BM dose and HT. Moreover, it does not increase GT and UT. The clinical benefit of pelvic active BM protection needs to be further validated in randomized controlled trials.; Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2021 Elsevier B.V. All rights reserved.)

Zhou, X., et al. (2023). "Efficacy and safety of Chinese patent medicine Xiao Yao San in polycystic ovary syndrome: A systematic review and meta-analysis." Journal of Ethnopharmacology 313: 116517.
	Ethnopharmacological Relevance: Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age worldwide. Previous studies using randomized controlled trials (RCTs) have revealed that Xiao Yao San (XYS), a classic Chinese patent medicine formula, can effectively treat PCOS. However, the entire evidence has yet to be systematically summarized.; Aim of the Study: The aim of this systematic review and meta-analysis of clinical trials was to assess the effect of XYS for the treatment of PCOS.; Materials and Methods: 7 databases were thoroughly reviewed for RCTs published from inception to July 2022, assessing the effect of XYS in treating PCOS, including Cochrane Library, PubMed, Embase, Wan Fang Database, Chinese Biomedical Database, China National Knowledge Infrastructure, and China Science and Technology Journal Database. Outcome measures included ovulation rate, pregnancy rate, hormonal levels, and glycemic parameters. Either a random-effects model or a fixed-effect models was used to pool data. Pooled effect sizes were reported as odds ratios (ORs) or standardized mean differences (SMDs) with their 95% confidence intervals (CIs).; Results: A total of 9 trials including 736 PCOS patients met the selection criteria. Our results indicate that XYS plus conventional medicines for PCOS significantly improved ovulation rate (OR = 2.45, 95% CI = 1.94 to 3.08, P < 0.001) and pregnancy rate (OR = 2.65, 95% CI = 1.87 to 3.75, P < 0.001), meanwhile decreased levels of fasting insulin (FINS) (SMD = - 0.46, 95% CI: 0.65 to - 0.27, P < 0.001) and homeostatic model assessment for insulin resistance (HOMA-IR) (SMD = - 0.65, 95% CI = - 0.93 to - 0.37, P < 0.001). XYS plus conventional medicines for PCOS did not have a significant impact on levels of total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and fasting plasma glucose (FPG). No serious adverse reactions were observed.; Conclusion: XYS combined with conventional medicines can improve ovulation and pregnancy rates, decrease FINS and HOMA-IR in PCOS patients, indicating that XYS treatment may be used as a promising adjuvant therapy to the conventional medicines of PCOS. However, due to significant heterogeneity and methodological shortcomings, these results should be interpreted with great caution. Larger, higher quality RCTs are needed to rigorously assess the effect of XYS as a complementary therapy in managing PCOS.; Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.)

Zhou, X., et al. (2020). "Acupuncture with or without moxibustion for primary dysmenorrhea: A protocol for a systematic review and meta-analysis." Medicine 99(38): e22395.
	Background: Primary dysmenorrhea (PD) occurs during menstrual cramps, and there is currently no pathological evidence. This disease severely affects the daily lives of young women. Acupuncture (ACU) and moxibustion are an excellent way to relieve the pain of patients with PD. And it has been widely utilizing. However, the effectiveness and safety of ACU and moxibustion in treating patients with PD are not confirmed by a high-quality meta-analysis. This work aims to evaluate ACU's efficacy and safety with or without moxibustion in the management of PD.; Methods: We will make a comprehensive retrieval in 9 databases as following: Embase; Cochrane Library; PubMed; Chinese databases SinoMed (previously called the Chinese Biomedical Database); Chinese National Knowledge Infrastructure; Chinese Scientific Journals Database; Wanfang Data. The time is limited from the construction of the library to August 2020. No restrictions about language and status. Our 2 authors will perform the selection of studies, the extraction of data, and the quality assessment with the risk of bias tool independently. We will use NoteExpressV3.2.0 and Excel2010 software to extract data. The content will be saved in electronic form. We will use the bias risk tool provided by the Cochrane Collaboration to evaluate the quality of the literature using RevMan 5.4 software. The primary outcome is the pain degree evaluation, including visual analog scale, numerical rating scale, Cox retrospective symptom scale, or any other scale used to evaluate the level of pain.Furthermore, the response rate involved an overall reduction in symptoms. The adverse effects and quality of life will be assessed as secondary outcomes. The risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data will be adopted to express the effect and safety of ACU with or without moxibustion for PD.; Results: The results of our study expect to provide high-quality, evidence-based recommendations on further treatment for clinicians.; Trial Registration Number: INPLASY202080006.; Conclusion: This study will provide scientific evidence of PD Systematic review.

Zhou, Y., et al. (2023). "Adjuvant Concurrent Chemoradiotherapy vs. Radiotherapy Alone in Cervical Cancer Patients with Intermediate-Risk Factors after Radical Surgery." International journal of radiation oncology biology physics 117(2 Supplement): e560.
	Purpose/Objective(s): For early-stage cervical cancer patients with intermediate-risk factors, there is no consensus about whether postoperative concurrent chemoradiotherapy (CCRT) is superior to radiotherapy (RT) alone. Materials/Methods: We retrospectively reviewed medical records of stage I-IIA cervical cancer patients underwent radical surgery and postoperative RT or CCRT from June 2012 to December 2017. Patients with any of the high-risk factors including positive pelvic lymph node, positive resection margin, and parametrial invasion were excluded. Patients with any of the intermediate-risk factors including large tumor size (>=4cm), deep stromal invasion (>=1/2), and lymphovascular space involvement were included. 1:1 propensity score matching was performed to balance baseline variables between patients receiving RT and CCRT. Result(s): A total of 350 patients were enrolled (84 underwent RT alone and 266 underwent CCRT). The median follow-up period was 50.4 months. For patients underwent RT alone and CCRT, the 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), the 5-year disease-free survival (DFS) rates were 90.6% and 91.4% (p = 0.733), respectively. 83 pairs of patients were enrolled based on propensity score matching. Similarly, there was no significant difference between OS or DFS rates of those matched patients. For patients with single intermediate-risk factor who received RT alone (n = 58) and CCRT (n = 132), the 5-year OS rates were 94.2% and 95.7% (p = 0.636), the 5-year DFS rates were 92.8% and 94.1% (p = 0.637). For patients with multiple intermediate-risk factors who received RT alone (n = 26) and CCRT (n = 134), the 5-year OS rates were 91.8% and 91.7% (p = 0.761), the 5-year DFS rates were 85.4% and 88.4% (p = 0.717). The cox regression analysis also indicated that adjuvant CCRT or RT was not an independent prognostic factor for OS or DFS. Otherwise, patients underwent CCRT seemed to develop a higher proportion of grade 3 or higher acute hematologic toxicities than RT group (45.5% and 14.3%, p<0.001). Conclusion(s): There was no significant difference in OS and DFS between cervical cancer patients with intermediate-risk factors receiving postoperative CCRT and RT alone. Patients underwent CCRT seemed to develop a higher proportion of severe hematologic toxicities than RT alone. To a certain extent, CCRT is not superior to RT alone for intermediate-risk patients.Copyright © 2023

Zhou, Z., et al. (2023). "The effects of metformin on anti-Müllerian hormone levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis." Journal of Ovarian Research 16(1): 123.
	Objective: To analyze whether metformin treatment in patients with polycystic ovary syndrome (PCOS) results in a decrease of anti-Müllerian hormone (AMH) levels, we reviewed and analyzed PCOS studies which evaluated serum AMH levels before and after metformin treatment.; Methods: This is a systematic review and meta-analysis of self-controlled clinical trials. Databases including PubMed, Embase, and Web of Science library were searched to identify eligible studies published before February 2023. Random-effects models were applied to assess standardized mean differences (SMDs) with 95% confidence intervals (95% CI).; Results: The electronic-based search retrieved 167 articles of which 14 studies (12 publications) involving 257 women with PCOS were included. In general, AMH levels decreased significantly after metformin treatment [SMD (95% CI) of -0.70 (-1.13 to -0.28); P = 0.001]. Metformin exhibited a strong inhibitory effect on AMH levels for PCOS patients with age less than 28 [SMD - 1.24, 95% CI - 2.15 to - 0.32, P = 0.008]. Additionally, AMH levels significantly slid down in PCOS patients with no more than 6 months metformin treatment [SMD - 1.38, 95% CI - 2.18 to - 0.58, P = 0.0007], or with no more than a dose of 2000 mg/day [SMD -0.70, 95% CI -1.11 to -0.28; P = 0.001]. Notably, suppressive effects of metformin treatment were merely observed in patients with AMH levels at baseline higher than 4.7 ng/ml [SMD - 0.66, 95% CI - 1.02 to - 0.31, P = 0.0003].; Conclusion: This meta-analysis provided quantitative evidence demonstrating that metformin significantly decreased AMH levels, especially for young patients and those with AMH levels at baseline higher than 4.7 ng/ml.; Trial Registration: PROSPERO CRD42020149182. (© 2023. The Author(s).)

Zhou, Z., et al. (2022). "Efficacy and safety of moxibustion in the treatment of female stress urinary incontinence: A protocol for systematic review and meta-analysis." Medicine (United States) 101(7): E28893.
	Background:Stress urinary incontinence (SUI) is one of the common diseases in female urinary system diseases, and the incidence is increasing year by year. Moxibustion therapy, as a kind of acupuncture therapy, has been widely used in the clinical treatment of SUI, but its therapeutic effect and safety have not been scientifically and systematically evaluated. Therefore, the protocol of this systematic review we propose this time is to scientifically evaluate the effectiveness and safety of moxibustion in the treatment of female stress urinary incontinence (FSUI). Method(s):The following 8 electronic databases will be searched from establishment to December 2021: PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database, Wanfang Database, China Biology Medicine disc. All randomized controlled trials of moxibustion in the treatment of FSUI will be searched in the above electronic databases. Two reviewers will independently complete research selection, data extraction, and research quality evaluation. After screening the studies, the quality of the included studies will be evaluated according to the quality standards specified in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). The primary outcome of included studies is the change from baseline in urine leakage measured by the 1-hour pad test. Secondary outcomes include: the short-form of the International Consultation on Incontinence Questionnaire, the mean 72-hour urinary incontinence episode frequency, self-assessment of the patient's treatment effect, severity of urinary incontinence, and adverse events. Two reviewers will independently conduct study selection, data extraction, risk of bias assessment, and study quality assessment. And the STATA 14.0 software will be implemented for data synthesis and meta-analysis. Result(s):The result of this meta-analysis will be submitted to peer-reviewed journals for publication, and a comprehensive review of current evidence will be conducted. Conclusion(s):The conclusion of this systematic review will provide evidence for judging whether moxibustion is a safer and more effective intervention for female stress urinary incontinence.Trial registration number:The protocol has been registered on INPLASY2021120052.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.

Zhou, Z., et al. (2023). "Comparison of acupuncture and moxibustion related non-surgical therapies for women with stress urinary incontinence: A systematic review and network meta-analysis of randomized controlled trials." Explore.
	Background: Stress urinary incontinence (SUI) significantly impacts women's health and imposes substantial mental and socio-economic burdens. Acupuncture and moxibustion, either alone or in combination with other non-surgical therapies, are recognized as effective treatments for SUI. This study aimed to assess the efficacy of various treatments for women with SUI using network meta-analysis (NMA). Method(s): We systematically searched databases up until June 30, 2022, to identify relevant randomized controlled trials (RCTs) focusing on SUI in women. Subsequently, the quality of the included studies was assessed. NMA was performed using STATA 14.0 software. Result(s): A total of 31 RCTs involving 2922 participants were included in the analysis. A total of 18 treatment plans were identified. The treatment plan consisting of Moxibustion + PFMT + EB demonstrated the most significant reduction in ICIQ-UI-SF. Due to lack of consistency across studies, a NMA was not performed for the outcomes of effectiveness and the 1 h pad test. Conclusion(s): The combined intervention of Moxibustion + PFMT + EB appears to be the most effective in reducing patients' reported symptoms and improving their quality of life. However, due to the limitations of the included studies, further high-quality RCTs are necessary to reinforce the current evidence.Copyright © 2023 Elsevier Inc.

Zhu, C., et al. (2022). "Effects of acupuncture on the pregnancy outcomes of frozen-thawed embryo transfer: A systematic review and meta-analysis." Frontiers in Public Health 10: 987276.
	Background: Acupuncture is increasingly used as adjuvant therapy for infertile women undergoing frozen-thawed embryo transfer (FET); however, its effects and safety are highly controversial. This study aimed to evaluate the pooled effects of adjuvant acupuncture on FET pregnancy outcomes.; Methods: We considered only randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture or no adjuvant treatment during FET and the primary outcome was clinical pregnancy rate. Two authors separately selected studies, extracted data, and performed a risk of bias assessment. Pooled data were expressed as risk ratio ( RR ) or mean difference ( MD ), with a 95% confidence interval ( CI ). In addition, we conducted subgroup and sensitivity analyses to investigate the sources of heterogeneity, and we also constructed funnel plots to assess the likelihood of publication bias. Finally, Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was applied to evaluate the quality of evidence.; Results: A total of 14 RCTs with a total of 1,130 participants were included in the study. We found significant effects of acupuncture adjuvant to FET on the outcomes of clinical pregnancy rate ( RR = 1.54, 95% CI [1.28, 1.85], I 2 = 34%; 14 trials), biochemical pregnancy rate ( RR = 1.51, 95% CI [1.21, 1.89]; 5 trials), endometrial thickness ( MD = 0.97, 95% CI [0.43, 1.51]; 12 trials), and endometrial pattern ( RR = 1.41, 95% CI [1.13, 1.75]; 7 trials). For live birth rate ( RR = 1.48, 95% CI [0.90, 2.43], 4 trials), there were no statistical effectiveness. For subgroup analyses, most variables had tolerable heterogeneity ( I 2 = 0%) except for trials that were sham-controlled, performed acupuncture only after FET, or <5 times, which appeared to interpret most of the heterogeneity. Additionally, the quality of evidence of all outcomes in this review ranged from low to moderate.; Conclusion: Acupuncture could be instrumental in the pregnancy outcomes of FET, and has very few risks of severe adverse events; however, the quality of evidence is unsatisfactory. Further research with rigorous methodological quality should be considered, and the protocols of acupuncture also need more investigations (e.g., appropriate control groups, sessions, and times).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Zhu, Xia, Huang, Zhang, Li, Yu, Ma and Zeng.)

Zhu, D., et al. (2022). "Effectiveness of physiotherapy for lower urinary tract symptoms in postpartum women: systematic review and meta-analysis." International Urogynecology Journal 33(3): 507-521.
	Introduction and hypothesis: The efficacy of physiotherapy for postpartum lower urinary tract symptoms (LUTS) has attracted considerable research interest. In the current study we evaluated the efficacy and safety of pelvic floor muscle training (PFMT) combined with biofeedback (BF), electrical stimulation (ES) therapy, or both for postpartum LUTS. Method(s): PUBMED, EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technique Journals Database, and Wanfang databases were searched from inception to December 2020. Eligible randomized controlled trials on postpartum LUTS comparing PFMT plus BF, ES, or both with PFMT alone were included. The Cochrane handbook was used to evaluate the quality of the studies. Result(s): Seventeen studies were included. The results of the meta-analysis showed that PFMT plus ES with or without BF was more effective than PFMT alone. Patients receiving PFMT plus ES and BF achieved greater improvement than controls receiving PFMT alone in incontinence quality of life scores (mean difference: 15.33, 95% confidence interval [CI]: 11.70-18.97, P < 0.00001), pelvic floor muscle strength (risk ratio: 2.29, 95% CI: 1.53-3.43, P < 0.0001), and urodynamic parameters (maximum urethral closure pressure, abdominal leak point pressure, and maximum urinary flow rate), and 1-h urine leakage (standardized mean difference: -0.70, 95% CI: -1.23 to -0.17, P = 0.010) also decreased. Conclusion(s): PFMT plus ES with or without BF exhibited better efficacy and safety for early postpartum LUTS than PFMT alone.Copyright © 2021, The International Urogynecological Association.

zhu, d. and x. zheng (2023). "Comparison of the effects of different electroacupuncture/transcutaneous electric nerve stimulation parameters on the outcome of IVF pregnancy: A systematic review and meta-analysis."
	Review question Comparison of the effects of different electroacupuncture/transcutaneous electric nerve stimulation parameters on the outcome of IVF pregnancy Searches Using the eight databases of PubMed, Cochrane, Web of Science, Embase, CNKI, WANFANG, VIP and CBM, a systematic literature search was conducted in August, 2023. The language was restricted to English and Chinese. Types of study to be included Female patients diagnosed with infertility and undergoing IVF-ET would be included. There were no restrictions in diagnosis criteria or participant age. IVF-ET with intracytoplasmic sperm injection (ICSI) was allowed. The outcomes included high-quality embryo rate, clinical pregnancy rate. The exclusion criteria were as following: (1) non-human studies; (2) non-RCTs studies; (3) studies without available date can be extracted; (4) non-original studies (letters, reviews, editorial). Condition or domain being studied Infertility, defined as failure to achieve pregnancy within 12 months of unprotected intercourse or therapeutic donor insemination in women younger than 35 years or within 6 months in women older than 35 years, affects up to 15% of couples. Currently, how to improve the success rate of in vitro fertilization has been a problem faced by researchers. Participants/population Female patients diagnosed with infertility and undergoing IVF-ET would be included. There were no restrictions in diagnosis criteria or participant age. IVF-ET with intracytoplasmic sperm injection (ICSI) was allowed. The outcomes included high-quality embryo rate, clinical pregnancy rate. The exclusion criteria were as following: (1) non-human studies; (2) non-RCTs studies; (3) studies without available date can be extracted; (4) non-original studies (letters, reviews, editorial). Intervention(s), exposure(s) Patients with infertility undergoing electroacupuncture/TENS. Comparator(s)/control Patients with infertility undergoing sham acupuncture or no adjuvant treatment. Main outcome(s) high-quality embryo rate, clinical pregnancy rate. Additional outcome(s) biochemical pregnancy rate, Number of retrieved oocytes.

Zhu, J., et al. (2021). "Efficacy of PD-1/PD-L1 inhibitors in ovarian cancer: a single-arm meta-analysis." Journal of Ovarian Research 14(1): 112.
	Several studies have evaluated the efficacy of PD-1/PD-L1 inhibitors in ovarian cancer; however, the response rate varies. This study aims to explore the efficacy of anti-PD-1/PD-L1 therapy in ovarian cancer. A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, and the Cochrane Library. The pooled ORR was calculated and compared. Fifteen trials were included in this meta-analysis. Our analyses showed that the pooled ORR of all included studies was 19% (95% CI: 13%, 27%). Single PD-1/PD-L1 inhibitors had the lowest ORR of 9% (95% CI: 7%, 12%), while the combination of PD-1/PD-L1 inhibitors and chemotherapy had the highest ORR of 36% (95% CI: 24%, 51%). This study showed that PD-1/PD-L1 inhibitors alone have limited efficacy for ovarian cancer. The combination of PD-1/PD-L1 inhibitors and chemotherapy could be chosen as the recommended modality for further study. (© 2021. The Author(s).)

Zhu, J., et al. (2023). "Phase II trial of tislelizumab plus bevacizumab and chemotherapy as the first-line therapy for persistent, recurrent, or metastatic cervical cancer: Updated efficacy and safety results." Immuno-Oncology and Technology 20(Supplement): 100572.
	Background: Patients (pts) with persistent, recurrent, or metastatic cervical cancer are at high risk of progression after first-line standard treatment with platinum-doublet chemotherapy +/- bevacizumab. Adding a PD-1 inhibitor to this standard treatment improves the survival of PD-L1+ pts. The preliminary results showed that tislelizumab plus bevacizumab and platinum-based chemotherapy had a promising efficacy with unconfirmed ORR of 78.4% (29/37, 95% CI, 61.8%-90.2%), irrespective of PD-L1 expression status (J Zhu, et al., JCO 2023 41:16_suppl). Here, we presented the updated results based on the full efficacy analysis set. Method(s): Eligible pts with persistent, recurrent, or metastatic cervical cancer received tislelizumab (200 mg, Q3W) plus bevacizumab (7.5 mg/kg, Q3W) and platinum-based chemotherapy. PD-L1 expression was accessed using VENTANA PD-L1(SP263) assay. The primary endpoint was PFS. Secondary endpoints were ORR, DCR, DOR and safety. Result(s): A total of 50 pts were enrolled, with 46 (92.0%) having squamous cell carcinoma. 41 pts were detected for PD-L1 expression; 35 (85.4%) pts were PD-L1+, 6 (14.6%) were PD-L1-. As of 10 Aug 2023, the median follow-up was 7.8 months (range 0.8-14.6). Among 47 pts in the efficacy analysis set, the confirmed ORR was 72.3% (34/47, 95% CI 57.4%-84.4%), with CR rate of 14.9% (6/47). Subgroup analysis showed that ORR for pts with squamous cell carcinoma and adenocarcinoma were 72.7% (32/44) and 66.7% (2/3), respectively; ORR for pts with PD-L1+ and PD-L1- tumors were 70.6% (24/34) and 100% (5/5), respectively. DCR was 100% (95% CI 92.4%-100.0%). Median DOR and PFS were not reached. After a median treatment duration of 6.8 months, grade >=3 treatment-related adverse events occurred in 48.0% of pts. Immune-related adverse events (irAE) were reported in 32.0% of pts, with no grade >=3 irAE reported. Serious adverse events occurred in 20.0% of pts. Conclusion(s): The updated results further demonstrated the efficacy and tolerability of tislelizumab plus bevacizumab and chemotherapy, with increased CR rate observed during extended treatment duration. Clinical trial identification: NCT05247619. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023

Zhu, J., et al. (2020). "Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy in the treatment of locally advanced cervical carcinoma: An updated meta-analysis based on randomized controlled trials." Medicine 99(1): e18663.
	Background: Radiotherapy concurrent with cisplatin is the standard regimen used for treatment of locally advanced cervical carcinoma. In this meta-analysis, survival, recurrence, compliance, and acute adverse effects were compared between weekly and triweekly cisplatin-based concurrent chemoradiotherapy regimens for treatment of cervical cancer.; Methods: A systematic search for relevant studies was conducted using PubMed, Cochrane Library, EMBASE, and Medline databases. Fixed- or random-effects models were used for pooled analysis. The endpoints were overall survival, recurrence, compliance, and acute adverse effects reported as odds ratios (ORs) and 95% confidence intervals (CIs).; Results: Eight randomized controlled trials met the inclusion criteria. No significant differences were observed between the 2 arms with respect to recurrence, survival, and acute adverse effects (all P > .05). However, the triweekly cisplatin regimen was associated with significantly lower incidence of local recurrence (OR, 1.72; 95% CI, 1.07-2.78; P = .03), radiotherapy completion (OR, 2.08; 95% CI, 0.99-4.38; P = .05), and anemia (OR, 2.10; 95% CI, 1.01-4.37; P = .05), while a weekly cisplatin regimen was associated with a lower risk of leukopenia (OR, 0.57; 95% CI, 0.42-0.92; P = .00) and thrombocytopenia (OR, 0.55; 95% CI, 0.31-0.97; P = .04).; Conclusions: Triweekly cisplatin-based chemotherapy significantly reduced local recurrence with tolerable toxicity and might be the optimal regimen in concurrent chemoradiotherapy for locally advanced cervical carcinoma.

Zhu, J.-Y., et al. (2021). "An Efficacy and Feasibility Analysis of Chinese Patent Medicine Combined With Letrozole in the Treatment of Women With Ovulation Disorders: A Network Meta-Analysis." Frontiers in Pharmacology 12: 722122.
	Objective: To compare the efficacy of various listed Chinese patent medicines combined with letrozole in the treatment of ovulation disorders using network meta-analysis (NMA). Methods: We conducted a systematic literature search in PubMed, Cochrane Central Register of Controlled Trials, Embase, Chinese Biomedical Literature, China National Knowledge Infrastructure, Wanfang, and VIP Information databases up to June 2020. Randomized controlled trials reporting Chinese patent medicine combined with letrozole for ovulation disorders were included. The Stata 13 and WinBUGS1.43 software were used for data analysis. Results: A total of 24 randomized controlled trials were included, involving 2,318 patients. The results showed that when compared with patients using only letrozole, the ovulation rate was higher in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, Fufang Xuanju capsules, or Dingkun Dan, and Fufan Xuanju capsules showed the greatest improvement; the pregnancy rate was higher in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, or Dingkun Dan; and the endometrial thickness on the day of follicular maturity was greater in patients using letrozole combined with Kuntai capsules, Fuke Zaizao capsules, Fufang Xuanju capsules, Bailing capsules, or Dingkun Dan. In terms of the sequencing of NMA results, Fufang Xuanju capsules combined with letrozole gave the best results in improving the ovulation rate and increasing the endometrial thickness, while Dingkun Dan combined with letrozole achieved the best results for improving the pregnancy rate. Conclusion: Letrozole combined with Chinese patent medicine is more effective than letrozole alone in the treatment of ovulation disorders. Fufang Xuanju capsules is good at improving the ovulation rate and increasing the endometrial thickness. Dingkun Dan is good at improving the pregnancy rate. The appropriate choice of treatment should be made according to the actual clinical situation. This study is registered with the International Prospective Register of Systematic Reviews (CRD42020200603).; Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Zhu, Liu, Cao and Wang.)

Zhu, X., et al. (2020). "Safety and effectiveness of acupuncture for POSEIDON patients in IVF/ICSI: A protocol for systematic review and meta-analysis." Medicine 99(42): e22768.
	Introduction: The purpose of this paper is to evaluate the efficacy and safety of acupuncture for POSEIDON patients undergoing IVF/ICSI.; Methods: and analysis We will electronically search Pubmed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. The clinical randomized controlled trials or quasi randomized controlled trials related to acupuncture treatment for POSEIDON patients in IVF/ICSI will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by two researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The clinical pregnancy rate (CPR) and live birth rate (LBR) will be the primary outcomes. The ongoing pregnancy, miscarriage rate (MR) and adverse events will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), while dichotomous data will be expressed in the form of relative risk with 95% CIs.; Ethics and Dissemination: The protocol of this systematic review (SR) does not require ethical approval because it does not involve humans. We will publish this article in peer-reviewed journals and presented at relevant conferences.; Systematic Review Registration: OSF Registries, DOI: 10.17605/OSF.IO/6WP2F (https://osf.io/6wp2f).

Zhu, Y., et al. (2024). "CircNUP50 is a novel therapeutic target that promotes cisplatin resistance in ovarian cancer by modulating p53 ubiquitination." Journal of nanobiotechnology 22(1): 35.
	Background: Most patients with ovarian cancer (OC) treated with platinum-based chemotherapy have a dismal prognosis owing to drug resistance. However, the regulatory mechanisms of circular RNA (circRNA) and p53 ubiquitination are unknown in platinum-resistant OC. We aimed to identify circRNAs associated with platinum-resistant OC to develop a novel treatment strategy.; Methods: Platinum-resistant circRNAs were screened through circRNA sequencing and validated using quantitative reverse-transcription PCR in OC cells and tissues. The characteristics of circNUP50 were analysed using Sanger sequencing, oligo (dT) primers, ribonuclease R and fluorescence in situ hybridisation assays. Functional experimental studies were performed in vitro and in vivo. The mechanism underlying circNUP50-mediated P53 ubiquitination was investigated through circRNA pull-down analysis and mass spectrometry, luciferase reporters, RNA binding protein immunoprecipitation, immunofluorescence assays, cycloheximide chase assays, and ubiquitination experiments. Finally, a platinum and si-circNUP50 co-delivery nanosystem (Psc@DPP) was constructed to treat platinum-resistant OC in an orthotopic animal model.; Results: We found that circNUP50 contributes to platinum-resistant conditions in OC by promoting cell proliferation, affecting the cell cycle, and reducing apoptosis. The si-circNUP50 mRNA sequencing and circRNA pull-down analysis showed that circNUP50 mediates platinum resistance in OC by binding p53 and UBE2T, accelerating p53 ubiquitination. By contrast, miRNA sequencing and circRNA pull-down experiments indicated that circNUP50 could serve as a sponge for miR-197-3p, thereby upregulating G3BP1 to mediate p53 ubiquitination, promoting OC platinum resistance. Psc@DPP effectively overcame platinum resistance in an OC tumour model and provided a novel idea for treating platinum-resistant OC using si-circNUP50.; Conclusions: This study reveals a novel molecular mechanism by which circNUP50 mediates platinum resistance in OC by modulating p53 ubiquitination and provides new insights for developing effective therapeutic strategies for platinum resistance in OC. (© 2024. The Author(s).)

Zhu, Y., et al. (2022). "Thermal ablation for cervical lymph node metastasis from papillary thyroid carcinoma: A meta-analysis." Medicine 101(51): e32193.
	Background: Traditionally, surgery has been the standard treatment for cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC). However, thermal ablation is currently recommended by several guidelines. This study aimed to evaluate the efficacy and safety of thermal ablation for lymph node metastasis in patients with PTC.; Methods: We searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases until March 2022 to collect studies on thermal ablation (including radiofrequency, microwave, and laser ablations) for cervical lymph node metastasis from PTC.; Results: A total of 190 patients were included, ranging from 5 to 39 in each study, with a sex ratio (male/female) ranging from 1/4 to 17/20, an average age ranging from 15.6 ± 3.0 to 62.3 ± 13.2 (yr), and a total of 270 cervical lymph nodes, ranging from 8 to 98. The follow-up results showed that thermal ablation significantly reduced the maximum diameter and volume of metastatic lymph nodes in PTC (P < .01). The pooled complete disappearance rate was 86% (95% confidence interval 79% to 93%). Thyroglobulin levels were significantly lower after surgery (P < .01). No major complications occurred, and the combined voice change rate was as low as 1% [CI 0% to 3%].; Conclusion: Our meta-analysis showed that thermal ablation is an effective and safe method for the treatment of cervical lymph node metastases from PTC. Considering the limitations of this study, more prospective, multicenter, large-sample studies are needed in the future.; Competing Interests: The authors have no funding and conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zhuang, H., et al. (2023). "Effect of Endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical cancer." Radiation Medicine and Protection 4(2): 104-108.
	Objective: To explore the value of Endostar in the clinical application of locally advanced cervical cancer. Method(s): A total of 107 patients with locally advanced cervical cancer who received concurrent chemoradiotherapy (CCRT) in the Department of Radiotherapy, the First Affiliated Hospital of Soochow University and Changzhou No.2 People's Hospital between January 2018 and December 2020 were enrolled in this retrospective study. There were 30 cases in the Endostar combined with CCRT (E-CCRT) group and 77 in the CCRT group. Propensity score matching (PSM) was used to reduce confounding factors. The short-term efficacy and long-term survival rate were compared between the E-CCRT group and the CCRT group. Result(s): After matching, the objective response rates in the E-CCRT group and CCRT group were 86.7% and 63.3%, respectively, with statistically significant difference (chi2 = 4.356, P = 0.037). But there were no statistically significant differences in the disease control rates (96.7% vs. 86.7%, chi2 = 0.873, P = 0.350), 3-year overall survival (OS) rates (86.7% vs. 83.3%, P = 0.681), and 3-year disease-free survival (DFS) rates (both 76.7% and 76.7%, P = 0.869). There was no statistically significant difference in the incidence of adverse reactions between the two groups. Conclusion(s): E-CCRT can improve the response of locally advanced cervical cancer patients without increasing the occurrence of adverse reactions, and has the potential to become a new treatment regimen for cervical cancer.Copyright © 2023 The Authors

Zhuang, Y. and H. Yang (2023). "The Significance of Radiotherapy in Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis." Cancer control : journal of the Moffitt Cancer Center 30: 10732748231179291.
	Objective: To assess the response rate and survival effect of adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) during ovarian clear cell carcinoma (OCCC).; Methods: We searched Web of Science, PubMed, Cochrane library electronic databases, Clinical Trials, WanFang Data and Chinese National Knowledge Infrastructure (CNKI) up to October 2022. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies.; Results: We identified a total of 4259 patients from 14 studies met the inclusion criteria. The pooled response rate of residual tumors for RT/CRT was 80.0%, the pooled 5-year progression-free survival (PFS) ratio during RT/CRT group was 61.0%, and the pooled 5-year overall survival (OS) ratio during RT/CRT group was 68.0%; heterogeneity tests demonstrated significant difference between studies (I 2 >50%). Cumulative results suggested adjuvant RT/CRT improved 5-year PFS ratio of OCCC patients (OR: 0.51 (95% CI: 0.42-.88), I 2 = 22%, P = .009), had no impact on 5-year OS ratio (OR: 0.52 (95% CI: 0.19-1.44), I 2 = 87%, P = .21); meta-regression of studies before and after 2000 found consistent results. Sub-analysis observed that adjuvant RT/CRT had no impact on 5-year OS ratio of early-stage (stage I + II) OCCC patients (OR: 0.67 (95% CI: 0.25-1.83), I 2 = 85%, P = .44), but might improve 5-year OS ratio of advanced and recurrent OCCC patients (OR: 0.13(95% CI: 0.04-.44), P = .001).; Conclusion: This analysis suggested that adjuvant RT/CRT might improve oncologic outcomes of OCCC, especially for advanced and recurrent cases. Due to the inherent selective biases of retrospective studies enrolled in the meta-analysis, more convincing evidences based on prospective randomized controlled trials (RCTs) are urgently needed.

zhuo, l., et al. (2022). "A systematic review and meta‐analysis comparing the effect of letrozole and clomiphene citrate in infertility women with polycystic ovary syndrome."
	Review question Is letrozole (LE) more effective than clomiphene citrate (CC) as ovulation induction agent in infertile women with polycystic ovary syndrome (PCOS) followed by timed intercourse (TI) or intrauterine insemination (IUI)? Searches We searched the following electronic databases, from inception to February 1，2022: PubMed，Web of Science，Embase, Cochrane Library, and Clinical Trials. We limit languages to English. The search strategies were based on combinations of “letrozole”,“clomiphene citrate” and “polycystic ovary syndrome”, using both free words and index terms. We further manually screened the references listed at the end of each retrieved article for additional references. Types of study to be included We will include randomized controlled trials reporting ovulation induction outcomes in infertile women with PCOS treated either with letrozole or clomiphene citrate followed by timed intercourse or intrauterine insemination. Review articles, commentaries, retrospective studies, observational studies, non-clinical trials, cell and animal studies will be excluded. Condition or domain being studied Polycystic ovary syndrome has become one of the most common causes leading to anovulatory infertility in child-bearing period female. Clomiphene citrate, an estrogen receptor modulator, has been recommended and used for many years as the first-line ovulation therapy for women with PCOS. However, in recent studies, letrozole, an aromatase inhibitor, was proved to be more effective in ovulation in PCOS, and have less side effects than CC. Therefore, we attended to perform a systematic review to compare the effect of letrozole and clomiphene citrate in infertility women with PCOS . Participants/population Inclusion: Infertile patients with PCOS, diagnosed as meeting the Rotterdam 2003 criteria. Exclusion: Patients who did not meet the Rotterdam 2003 criteria; patients with Letrozole or clomiphene resistance, or patients with another known cause of infertility. Intervention(s), exposure(s) Letrozole without any adjuncts in any dose. Ovulation induction therapy with letrozole followed by timed intercourse or intrauterine insemination. Comparator(s)/control Clomiphene citrate without any adjuncts in any dose. Ovulation induction therapy with letrozole followed by timed intercourse or intrauterine insemination. Main outcome(s) Ovulation rate，clinical pregnancy rate，and live birth rate. Measures of effect Risk ratio (RR), 95% confidence interval (CI). Additional outcome(s) Miscarriage rate，multiple pregnancy rate，endometrial thickness on the day of human chorionic gonadotrophin (HCG) administration or the day of maximum follicle growth. Measures of effect Risk Ratio, 95% confidence interval (CI). Endometrial thickness: measured as mean ± standard deviation (SD).

Zi, D., et al. (2022). "Critical Steps to Performing a Successful Single-site Laparoscopic Myomectomy for Large Pedunculated Myoma during Pregnancy." Journal of Minimally Invasive Gynecology 29(7): 818-819.
	Study Objective: To demonstrate tips and tricks for the successful use of single-site laparoscopic surgery for pedunculated myomectomy during pregnancy. Design(s): Stepwise demonstration with narrated video footage. Setting(s): An academic tertiary care hospital affiliated with Baylor College of Medicine. Our patient is a 39-year-old pregnant G1P0010 with a symptomatic 12-cm degenerating pedunculated myoma refractory to conservative pain management. Intervention(s): Recent literature has indicated that most laparotomic myomectomies performed during pregnancy showed overall positive pregnancy outcomes and low complications. This indicates that myomectomy in pregnancy is safe and can be used in cases unresponsive to conservative management [1]. However, cases in literature discussing the single-site techniques for laparoscopic myomectomy during pregnancy have been sparse [2]. Four case series were reviewed; a total of 62 pregnant patients underwent laparoendoscopic single-site surgery without any complications [3-6]. Using laparoscopy in myomectomy compared with laparotomy during pregnancy permits decreased postoperative pain, quicker recovery, and lowered risk of postoperative complications [5,7,8]. Single-site laparoscopic surgery also aids in improved patient cosmesis and can be used for the myoma removal. Literature has demonstrated that single-site laparoscopy is safe and feasible during all stages of pregnancy [3,4]. Nevertheless, this approach may be challenging for inexperienced surgeons owing to the lack of triangulation and crowding of instruments in single-site laparoscopy [5]. At 21 weeks and 3 days pregnancy, our patient underwent single-incision laparoscopic surgery myomectomy. A 2.5-cm skin incision was made at the umbilicus to the abdominal cavity, and a GelPOINT Mini was inserted. Through the laparoscope, we can observe that a 12-cm pedunculated myoma was protruding from the right uterine fundus on a 4-cm stalk. A 0-Vicryl suture was tied around the base of the stalk. The stalk was then cauterized with bipolar energy and transected with the harmonic scalpel, completely detaching the myoma. Subsequently, an Endo Catch bag was placed around the myoma and brought up to the umbilical incision. Using a scalpel, bag-contained morcellation was completed within 22 minutes and the contents removed. As a result, the estimated blood loss was 50 cc and the total operative time was 123 minutes. The extended operating time was caused by slow movements to avoid disrupting the fetus. She had an unremarkable postoperative course, no medications were needed for pain management, and she was discharged home on postoperative day 2. At 38 weeks, she successfully delivered with elective cesarean delivery with no complications. Histopathology showed fragments of leiomyoma with diffuse necrosis. Tips and tricks: 1. Single-site entry technique uses the open Hasson technique, which reduces the risk of injury to the pregnant uterus and dilated surrounding vessels. 2. Through a 2.5-cm incision, the surgeon placed a suture in the myoma stalk because other hemostasis agents such as vasopressin are contraindicated in pregnancy. 3. Owing to difficulties related to single-site surgery, the surgeon should possess extensive expertise in single-site surgery. 4. Manipulation of the uterus should be minimized to reduce the disturbance of the pregnant uterus. 5. V-loc suture allows for faster and simplified uterine incision closure. 6. If the surgeon encounters excessive difficulty during the surgery, a 5-mm accessory port can be placed. 7. During tissue extraction, gentle traction should be used to reduce provoking the pregnant uterus. 8. When transecting the myoma stalk, it is important to leave a stump of more than 1 cm to increase suturing ease and prevent accidental suturing of the uterus. Conclusion(s): Single-incision laparoscopic surgery myomectomy for pedunculated myoma may be a practical technique in women refractive to conservative management. When performed by an experienced surgeon, the patient may benefit from faster specimen removal and recovery.Copyright © 2022 AAGL

Zi, D., et al. (2022). "CXCR4 knockdown enhances sensitivity of paclitaxel via the PI3K/Akt/mTOR pathway in ovarian carcinoma." Aging 14(11): 4673-4698.
	Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. EOC control remains difficult, and EOC patients show poor prognosis regarding metastasis and chemotherapy resistance. The aim of this study was to estimate the effect of CXCR4 knockdown-mediated reduction of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) stemness and enhancement of chemotherapy sensitivity in EOC. Mechanisms contributing to these effects were also explored. Our data showed distinct contribution of CXCR4 overexpression by dependent PI3K/Akt/mTOR signaling pathway in EOC development. CXCR4 knockdown resulted in a reduction in CSCs and EMT formation and enhancement of chemotherapy sensitivity in tumor cells, which was further advanced by blocking CXCR4-PI3K/Akt/mTOR signaling. This study also documented the critical role of silencing CXCR4 in sensitizing ovarian CSCs to chemotherapy. Thus, targeting CXCR4 to suppress EOC progression, specifically in combination with paclitaxel (PTX) treatment, may have clinical application value.

Zick, S. M., et al. (2021). "Acupressure for cancer-fatigue in ovarian cancer survivor (The AcuOva Study): A community-based clinical trial study protocol examining the impact of self-acupressure on persistent cancer related fatigue in ovarian cancer survivors." Contemporary Clinical Trials 107: 106477.
	Background Persistent cancer-related fatigue is one of the most common and burdensome symptoms experienced by ovarian cancer survivors. Despite the high burden of fatigue in ovarian cancer survivors, there are few available treatments. Previous research has shown self-acupressure to be a safe method for improving persistent fatigue, sleep, and quality of life among fatigued breast cancer survivors, yet there are no studies examining self-acupressure for fatigue in ovarian cancer survivors. Methods A three group parallel, randomized controlled trial will be conducted to evaluate the efficacy of self-acupressure taught and delivered via a patient-designed, custom-built mobile app ("MeTime") and accompanying hand-held device ("AcuWand") to help guide correct pressure application. A sample of 165 ovarian cancer survivors, who have completed primary cancer treatment will be recruited from tumor registries in Michigan and Los Angeles. Participants will be mailed a tablet preloaded with the app and a device, and all visits will be conducted remotely. Participants will be randomized to 6-weeks of daily self-acupressure via the app and device, or a sham app and device, or no care group. Self-report measures will be completed at baseline, 6-weeks (post-intervention), 3-, and 6-months. Primary outcome is the Brief Fatigue Inventory; secondary outcomes are sleep, quality of life, and symptoms commonly associated with persistent fatigue. Discussion An app based self-acupressure treatment may be an easily-accessible and inexpensive treatment to reduce fatigue in ovarian cancer survivors. The results of the study will provide information on the possible benefits of app-based self-acupressure for fatigue in ovarian cancer survivors. Trial registration: This study is registered at ClinicalTrials.gov Identifier: NCT03763838, date registered on December 4, 2018.Copyright © 2021 Elsevier Inc.

Zidan, S., et al. (2023). "Could psychobiotics and fermented foods improve mood in middle-aged and older women?" Maturitas 181: 107903.
	Menopause is a natural physiological phase during which women experience dramatic hormonal fluctuations. These lead to many symptoms, such as depression and anxiety, which, in turn, can negatively affect quality of life. Proper nutrition has an influential role in alleviating depression as well as anxiety. It is well known that gut microbiota dysbiosis contributes to the development of mood disorder. There is mounting evidence that modulating the gut-brain axis may aid in improving mood swings. In this context, this narrative review summarizes recent findings on how aging changes the composition of the gut microbiota and on the association between gut microbiota and mood disorders. In addition, it evaluates the effectiveness of psychobiotics and fermented foods in treating mood swings in middle-aged and older women. A search was done using PubMed, Scopus, and Google Scholar, and thirteen recent articles are included in this review. It is evident that psychobiotic supplementation and fermented foods can improve mood swings via several routes. However, these conclusions are based on only a few studies in middle-aged and older women. Therefore, long-term, well-designed randomized controlled trials are required to fully evaluate whether psychobiotics and fermented foods can be used to treat mood swings in this population.

Ziegler, C., et al. (2022). "Abstract No. 139 Intravenous versus oral pain medications after uterine fibroid embolization: comparison of changes in pain score." Journal of Vascular and Interventional Radiology 33(6 Supplement): S65.
	Purpose: Pain after uterine fibroid embolization (UFE) is managed with different pain medication regimens based on interventionalist preference. The purpose of this study was to compare post-UFE pain when managed with an intravenous (IV) regimen versus an oral regimen. Material(s) and Method(s): The records of adult (>=18 years) females who underwent UFE between 2018-2019 were reviewed retrospectively while those between 2020-2021 were reviewed prospectively. Between 2018-2019 patients received an IV regimen: postprocedural hydromorphone PCA and IV ketorolac. Between 2020-2021 patients received an oral regimen: preprocedural and postprocedural PO acetaminophen and gabapentin, and postprocedural PO ibuprofen and PO opiates. IV opiates were available in the oral regimen for breakthrough pain only. The primary outcome was change in pain score between baseline and 2 hours (2H), 4 hours (4H), morning after UFE (MA), and upon discharge (DC). Mean change in pain scores for the IV and oral regimen at 2H, 4H, MA and DC were compared using the two-tailed t-test (P=0.05). Result(s): Seventy-six patients were included 40 received the IV regimen and 31 the oral regimen. There was no significant difference in the change in pain score between the IV and oral regimens at 2H (P=0.24), 4H (P=0.52), MA (P=0.17) or DC (P=0.61) (Table 1). Of the 31 patients in the oral regimen, 18 (58%) required IV opiates for breakthrough pain. Five (16%) received only one dose of IV opiates. All 18 patients required their first IV opiate dose within 3 hours of procedure completion. Conclusion(s): There was no significant difference in the change in pain scores at different postprocedural time points between patients who received IV versus oral medication regimens. Although more than half of patients who received the oral regimen required IV opiates for breakthrough pain, all required the first dose within 3 hours of procedure completion. This suggests that patients who do not require IV opiates within the first 3 post procedure hours can successfully be discharged on oral medications only. Further research is needed to optimize a post-UFE oral medication regimen. [Formula presented]Copyright © 2022

Ziegler, N. and L. De Wilde Rudy (2022). "Reduction of adhesion formation after gynaecological adhesiolysis surgery with 4DryField PH - a retrospective, controlled study with second look laparoscopies." Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 42(4): 658-664.
	Adhesions are a common consequence of abdomino-pelvic surgery. Efficacy of available adhesion prevention agents is discussed controversially. Here, we used the adhesion barrier 4DryField PH: a powder, which is transformed into a barrier gel with saline solution. The study includes 40 consecutive patients with surgeries for adhesiolysis, endometriosis and other gynaecological pathologies and subsequent second look interventions. The intervention group ( n = 17) received 4DryField PH gel while control patients ( n = 23) did not receive any adhesion prevention. Severity and extent of adhesion formation were scored during both interventions using an established score. Direct comparison between first and second interventions showed that extent and severity of adhesions could be reduced significantly using 4DryField PH gel. In contrast, in the control group, extent was not reduced and severity was even significantly higher. Direct comparison of second look laparoscopies revealed that adhesion extent and severity were significantly lower in the 4DryField PH than in the control group.Impact Statement What is already known on this subject? Adhesion formation after gynaecologic surgeries is known to be frequent and highly problematic as it directly induces complications and additionally makes subsequent surgeries more difficult. The effectiveness of established adhesion barriers is not sufficient to tackle these problems adequately. What the results of this study add? This is the first controlled study using the relatively new adhesion barrier 4DryField PH. It yields a significant reduction of extent as well as severity of adhesions, while adhesiolysis surgery alone does not solve the problem. What the implications are of these findings for clinical practice and/or further research? Usage of 4DryField PH gel seems to be a good approach to solve the adhesion problem of gynaecologic surgery in general and the reformation problem of adhesiolysis surgery specifically. The results should be confirmed in a larger prospective randomised controlled trial.

Žigová, L., et al. (2022). "Neuroactive steroids - new possibilities in the treatment of postpartum depression." Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti 71(4): 142-150.
	Pregnancy and postpartum period are associated with demanding physical and psychological changes that often lead to the development of psychological disorders. Depression is diagnosed in more than one in six women after childbirth. However, the prevalence of postpartum depression can be much higher because many cases are undiagnosed. In the case of severe depression, the patient is switched to pharmacological treatment, with sertraline being the most commonly used for this diagnosis. A new drug used in the treatment of postpartum depression is brexanolone, which was registered by FDA in 2019. The advantage over conventional therapy is its rapid onset of action. The structure represents the neuroactive steroid - allopregnanolone, which acts as an agonist on the &#948;-subunit of the GABA receptor and improves the symptoms of postpartum depression. In addition to the registered brexanolone, another steroidal drug, zuranolone, is available in the third phase of the clinical trial. The steroid structure was chemically altered to improve bioavailability and create an oral dosage form. Another synthetic analogue of neuroactive allopregnanolone, known as ganaxolone, did not show a significant reduction in depressive symptoms in the second phase of the clinical trial compared to placebo. Nevertheless, it has great therapeutic potential in the treatment of various types of epilepsy.

Zilaee, M., et al. (2020). "The effects of soy isoflavones on total testosterone and follicle-stimulating hormone levels in women with polycystic ovary syndrome: a systematic review and meta-analysis." The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception 25(4): 1-6.
	Objectives: The aims of this systematic review and meta-analysis were to evaluate the effectiveness of soy isoflavones on serum levels of total testosterone (TT) and follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS).Methods: A meta-analysis was performed by searching for relevant randomised controlled trials (RCTs) in several databases. Of the four trials found, the eligibility criteria to evaluate the efficacy of soy isoflavones on serum levels of FSH were met by three trials and of TT by four trials. The Cochrane scale was used to evaluate the risk of bias. Fixed-effects and random-effects models were used to evaluate overall effect. The χ2 test (Cochran's Q test) and the I2 index were used to assess the heterogeneity of RCTs.Results: Our results showed that soy isoflavones significantly decreased TT (weighted mean difference [WMD] - 0.14; 95% confidence interval [CI] - 0.2, -0.02; p = 0.016; I2 = 89%, p < 0.001) but had no significant effect on FSH levels (WMD -0.25; 95% CI -0.54, 0.02; p = 0.06; I2 = 0%, p = 0.85).Conclusion: Although the results of this meta-analysis showed that soy isoflavones in women with PCOS decreased TT and had no significant effect on FSH, better and more valid studies are needed to confirm these results.

Zimmermann, A., et al. (2023). "Impact of moderate-to-severe endometriosis on IVF cumulative live birth rate: a retrospective matched cohort study." Reproductive Biomedicine Online 47(3): 103186.
	Research Question: Does moderate-to-severe endometriosis have an impact on cumulative live birth rates (cLBR) and IVF outcomes?; Design: In this retrospective matched cohort study, women with moderate-to-severe endometriosis undergoing IVF or intracytoplasmic sperm injection treatment from January 2015 to December 2020 were matched 1:2 to women with other causes of infertility (control group). The main outcome was cLBR per cycle and per woman, and secondary outcomes were number of oocytes retrieved and number of mature oocytes, fertilization rate, total number of embryos and usable embryos, implantation rate, clinical pregnancy rate and miscarriage rate per cycle.; Results: In total, 195 women with endometriosis were matched with 390 women without endometriosis (323 and 646 cycles, respectively). Women with endometriosis had significantly fewer oocytes retrieved than women in the control group (P=0.003) despite higher doses of gonadotropins, but had a similar number of mature oocytes, fertilization rate, and total number of embryos and usable embryos. cLBR per cycle and per women did not differ significantly between the endometriosis group and the control group (19.8% versus 24.3%, P = 0.12; 32.3% versus 37.2%, P = 0.24, respectively). In women with endometrioma, a history of cystectomy did not impact cLBR per cycle (28.3% versus 31.9%, P = 0.68). We did not observe any significant impact of tobacco use in the endometriosis group compared with the control group (16.4% versus 25.9%, P = 0.13).; Conclusion: This matched cohort study did not observe a significant impact of moderate-to-severe endometriosis on cLBR among women undergoing IVF. These data are reassuring for the counselling of infertile women with endometriosis before IVF. (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Zimmermann Julia, S. M., et al. (2023). "Laparoscopic Fertility-Sparing Surgery for Early Ovarian Malignancies." Cancers 15(20).
	The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after laparoscopic FSS are sparse, but some retrospective studies have shown that open FSS may be offered to selected patients. We assessed the role of minimally invasive FSS in comparison with radical surgery (RS) in terms of oncological safety and reproductive outcomes after FSS in this multicenter study. Eighty patients with FIGO stage I/II ovarian cancer treated with laparoscopic FSS or RS between 01/2000 and 10/2018 at the participating centers (comprehensive gynecological cancer centers with minimally invasive surgical expertise) were included in this retrospective analysis of prospectively kept data. Case-control ( n = 40 each) matching according to the FIGO stage was performed. Progression-free survival [150 (3-150) and 150 (5-150) months; p = 0.61] and overall survival [36 (3-150) and 50 (1-275) months; p = 0.65] did not differ between the FSS and RS groups. Eight (25.8%) women became pregnant after FSS, resulting in seven (22.5%) deliveries; three (37.5%) patients conceived after in vitro fertilization, and five (62.5%) conceived spontaneously. Laparoscopic FSS seems to be applicable and oncologically safe for patients with early-stage ovarian cancer, with adequate fertility outcomes.

Zimmermann, M., et al. (2023). "Can psychological interventions prevent or reduce risk for perinatal anxiety disorders? A systematic review and meta-analysis." General Hospital Psychiatry 84: 203-214.
	Objective: Little is known about the extent to which interventions can prevent perinatal anxiety disorders. We conducted a systematic review and meta-analysis to examine whether interventions can decrease the onset and symptoms of perinatal anxiety among individuals without an anxiety disorder diagnosis. Method(s): We conducted a comprehensive literature search across five databases related to key concepts: (1) anxiety disorders/anxiety symptom severity (2) perinatal (3) interventions (4) prevention. We included studies that examined a perinatal population without an anxiety disorder diagnosis, included a comparator group, and assessed perinatal anxiety. We included interventions focused on perinatal anxiety as well as interventions to prevent perinatal depression or influence related outcomes (e.g., physical activity). Result(s): Thirty-six studies were included. No study assessing the incidence of perinatal anxiety disorder (n = 4) found a significant effect of an intervention. Among studies assessing anxiety symptom severity and included in the quantitative analysis (n = 30), a meta-analysis suggested a small standardized mean difference of -0.31 (95% CI [-0.46, -0.16], p < .001) for anxiety at post intervention, favoring the intervention group. Both mindfulness (n = 6), and cognitive behavioral therapy approaches (n = 10) were effective. Conclusion(s): Interventions developed for perinatal anxiety were more effective than interventions to prevent perinatal depression. Psychological interventions show promise for reducing perinatal anxiety symptom severity, though interventions specifically targeting anxiety are needed.Copyright © 2023 Elsevier Inc.

Zimmer-Stelmach, A., et al. (2022). "The Application of Artificial Intelligence-Assisted Colposcopy in a Tertiary Care Hospital within a Cervical Pathology Diagnostic Unit." Diagnostics (Basel, Switzerland) 12(1).
	The rising global incidence of cervical cancer is estimated to have affected more than 600,000 women, and nearly 350,000 women are predicted to have died from the disease in 2020 alone. Novel advances in cancer prevention, screening, diagnosis and treatment have all but reduced the burden of cervical cancer in developed nations. Unfortunately, cervical cancer is still the number one gynecological cancer globally. A limiting factor in managing cervical cancer globally is access to healthcare systems and trained medical personnel. Any methodology or procedure that may simplify or assist cervical cancer screening is desirable. Herein, we assess the use of artificial intelligence (AI)-assisted colposcopy in a tertiary hospital cervical diagnostic pathology unit. The study group consisted of 48 women (mean age 34) who were referred to the clinic for a routine colposcopy by their gynecologist. Cervical images were taken by an EVA-Visualcheck TM colposcope and run through an AI algorithm that gave real-time binary results of the cervical images as being either normal or abnormal. The primary endpoint of the study assessed the AI algorithm's ability to correctly identify histopathology results of CIN2+ as being abnormal. A secondary endpoint was a comparison between the AI algorithm and the clinical assessment results. Overall, we saw lower sensitivity of AI (66.7%; 12/18) compared with the clinical assessment (100%; 18/18), and histopathology results as the gold standard. The positive predictive value (PPV) was comparable between AI (42.9%; 12/28) and the clinical assessment (41.8%; 18/43). The specificity, however, was higher in the AI algorithm (46.7%; 14/30) compared to the clinical assessment (16.7%; 5/30). Comparing the congruence between the AI algorithm and histopathology results showed agreement 54.2% of the time and disagreement 45.8% of the time. A trained colposcopist was in agreement 47.9% and disagreement 52.1% of the time. Assessing these results, there is currently no added benefit of using the AI algorithm as a tool of speeding up diagnosis. However, given the steady improvements in the AI field, we believe that AI-assisted colposcopy may be of use in the future.

Ziv, E. and T. Erlich (2022). "Novel, disposable, self-inserted, vaginal device for the non-surgical management of pelvic organ prolapse: efficacy, safety, and quality of life." BMC Women's Health 22(1): 459.
	Background: We evaluated a novel disposable, collapsible, ring-shaped vaginal device that is self-inserted within an applicator and removed with a string. The device was developed to overcome the drawbacks of existing ring pessaries for non-surgical pelvic organ prolapse management (POP).; Methods: The primary objective efficacy endpoint of this prospective, interventional, multicenter, self-controlled, and home-use study was the proportion of subjects with improved staging on the Pelvic Organ Prolapse Quantification (POP-Q) scale. Subjective efficacy was assessed using the POP symptoms alleviation score. Safety was evaluated by recording the rate and incidence of adverse events (AEs) in a daily diary, and quality of life (QoL) was evaluated using the modified Pelvic Floor Impact (PFIQ-7) and Pelvic Floor Disability Index (PFDI-20) questionnaires.; Results: A total of 94 usage cycles were observed in a group of 52 participants (mean age 60.2 ± 10.5 years, 81.1% postmenopausal) who used the device for 3558 days. Of these, 24 participants completed one usage cycle, 14 completed two usage cycles, and 14 completed three usage cycles with 28-45 days of ProVate use in each usage cycle. All patients experienced greater than two POP-Q stage reductions. The descent was completely reduced to POP-Q stage 0 in 97.8% of participants. The POP symptom alleviation questionnaire showed significant subjective efficacy (P < 0.0001). The modified PFDI-20 and PFIQ-7 scores also improved substantially (P < 0.0001 for both). There were 91 nonserious device-related AEs: 98.9% were mild and 87.9% anticipated, with no vaginal infection, and one case of urinary tract infection.; Conclusion: The novel device substantially reduces prolapse and provides significant subjective POP symptom relief and QoL improvement, with minimal AEs. The device may enable women to self-manage their prolapse with a small, disposable device that minimizes self-touching and frequent dependency on the clinic.; Trial Registration: Clinical.; Trials: gov , NCT02239133 , posted September 12, 2014 (retrospectively registered). (© 2022. The Author(s).)

Ziv, E. and T. Erlich (2023). "A randomized controlled study comparing the objective efficacy and safety of a novel self-inserted disposable vaginal prolapse device and existing ring pessaries." Frontiers in Medicine 10: 1252612.
	Introduction: ProVate is a novel, disposable, collapsible self-inserted vaginal device for the nonsurgical management of pelvic organ prolapse (POP). We assessed possible vaginal microflora changes and POP reduction using ProVate and a commercially available ring pessary (control).; Methods: We performed post-hoc analysis of data obtained from an interventional, prospective, multicenter, open-label, randomized, controlled, statistically powered (noninferiority), home-use, cross-over study conducted at seven sites. Safety and performance data collected for both devices were analyzed to compare objective POP reduction (employing the Pelvic Organ Prolapse Quantification System [POP-Q]), safety (assessed by the incidence of adverse events [AEs]), and the rates of certain AEs.; Results: Eighty-five women with symptomatic POP were screened; 71 were randomized, and 58 completed the study per protocol. Forty-nine (90.7%) ProVate users experienced complete prolapse reduction (stage 0), 3 (5.6%) experienced reductions to POP-Q stage 1, and 2 (3.7%%) experienced reductions to stage 2. Collectively, 52/54 (96.3%) ProVate users experienced prolapse reduction to stage 0 or 1. In all, 47/57 (82.5%) control users experienced complete prolapse reduction, while 5 (8.8%), 4 (7.0%), and 1 (1.8%) experienced reductions to stage 1, 2, and stage 3, respectively. Collectively, 52/57 (91.2%) control users experienced reductions to either stage 0 or 1. In 53/54 (98.1%) ProVate and 55/57 (96.5%) control users, there was at least 1 POP-Q stage prolapse reduction, and in 32 (91.4%) ProVate and 31 (83.8%) control users who had stage ≥3 prolapse, there were at least three POP-Q stage reductions. In total, 26/71 (36.6%) ProVate and 22/64 (34.4%) control users in the safety population experienced AEs. The incidence of device-related AEs was 17/71 (23.9%) for ProVate and 13/64 (20.3%) for the control. Most AEs were minor, mild, and anticipated.; Conclusion: Our analysis demonstrated that ProVate and the control are highly effective in reducing POP, and both are associated with comparably low numbers of AEs. However, ProVate has the advantage of being more user-friendly, suitable for home use, and expected to allow women with POP to practice better and easier self-care.; Competing Interests: EZ has a conflict of interest as he is an employee and shareholder of ConTIPI Medical, the company that developed the studied device. EZ took part in the design of the study, data collection, interpretation of the results, and manuscript writing. TE has a conflict of interest as she is a consultant and optionee at ConTIPI Medical, the company that developed the studied device. TE took part in the design of the study, interpretation of results, and manuscript writing. (Copyright © 2023 Ziv and Erlich.)

Zivanovic, I., et al. (2023). "Nd: yAG/Er: YAG dual laser compared with topical steroid to treat vulvar lichen sclerosus: a randomised controlled trial." BJOG.
	Objective: To evaluate the efficacy and safety of a novel non‐ablative Nd:YAG/Er:YAG dual laser treatment for vulvar lichen sclerosus (LS) in comparison with the recommended first‐line therapy with topical steroid. Design: A randomised investigator‐initiated active‐controlled trial. Setting: Single tertiary referral centre. Population: Women with vulvar LS. Methods: Randomisation (2:1) to Nd:YAG/Er:YAG laser therapy or topical clobetasol proprionate therapy. Four laser treatments at 0, 1, 2 and 4 months or decreasing doses of steroid for 6 months. Main Outcome Measures: The primary outcome was the change in objective validated clinical LS score in the laser arm between baseline and 6 months. Secondary outcomes were laser tolerability/safety, symptom scores and patient satisfaction. Results: Sixty‐six women were included, 44 in the laser group and 22 in the steroid group. The total LS score decreased by −2.34 ± 1.20 (95% CI −2.71 to −1.98) in women treated with laser compared with a decrease of −0.95 ± 0.90 (95% CI −1.35 to −0.56) in those receiving steroid applications (p < 0.001). Laser treatment was safe and well tolerated. Subjective severity scores (on visual analogue scale) and vulvovaginal symptoms questionnaire scores improved similarly for the laser and steroid arms without significant differences between the two treatments. Patient satisfaction was higher in the laser arm than in the steroid arm (p = 0.035). Conclusions: Non‐ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6‐month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.

Zivanovic, O., et al. (2021). "Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: an MSK Team Ovary Phase II Study." Journal of Clinical Oncology 39(23): 2594‐2604.
	PURPOSE: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin‐based chemotherapy, respectively. Based on a binomial single‐stage pick‐the‐winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post‐surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS: Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard‐arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1‐sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1‐sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow‐up of 39.5 months, 82 patients progressed and 37 died. The median progression‐free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION: HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum‐sensitive recurrent ovarian cancer.

Zolfaroli, I., et al. (2023). "Correction to: Impact of Endometrial Receptivity Analysis on Pregnancy Outcomes In Patients Undergoing Embryo Transfer: A Systematic Review and Meta-Analysis." Journal of Assisted Reproduction and Genetics 40(5): 995.
	
Zolfaroli, I., et al. (2023). "Impact of Endometrial Receptivity Analysis on Pregnancy Outcomes In Patients Undergoing Embryo Transfer: A Systematic Review and Meta-Analysis." Journal of Assisted Reproduction and Genetics 40(5): 985-994.
	To analyze the influence of endometrial receptivity analysis (ERA) on embryo transfer (ET) results in patients undergoing in vitro fertilization (IVF) treatment. PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched from inception up to December 2022 for studies comparing pregnancy outcomes in patients undergoing personalized embryo transfer (pET) by ERA versus standard ET. Data were pooled by meta-analysis using a random effects model. We identified twelve studies, including 14,224 patients. No differences were observed between patients undergoing ERA test and those not undergoing ERA test prior to ET in terms of live birth (OR 1.00, 95% CI 0.63-1.58, I 2 = 92.7%), clinical pregnancy (OR 1.20, 95% CI 0.90-1.61, I 2 = 86.5%), biochemical pregnancy (OR 0.83, 95% CI 0.46-1.49, I 2 = 87%), positive pregnancy test (OR 0.99, 95% CI 0.80-1.22, I 2 = 0%), miscarriage (OR 0.91, 95% CI 0.62-1.34, I 2 = 67.1%), and implantation rate (OR 1.18, 95% CI 0.44-3.14, I 2 = 93.2%). pET with ERA is not associated with any significant differences in pregnancy outcomes as compared to standard ET protocols. Therefore, the utility of ERA in patients undergoing IVF should be revisited. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zolfaroli, I., et al. (2023). "Outcomes in patients undergoing embryo transfer: a systematic review and meta-analysis." Journal of Assisted Reproduction and Genetics.
	To analyze the influence of endometrial receptivity analysis (ERA) on embryo transfer (ET) results in patients undergoing in vitro fertilization (IVF) treatment. PubMed, Embase, Cochrane Central Register of Controlled Trials, and BioMed Central databases were searched from inception up to December 2022 for studies comparing pregnancy outcomes in patients undergoing personalized embryo transfer (pET) by ERA versus standard ET. Data were pooled by meta-analysis using a random effects model. We identified twelve studies, including 14,224 patients. No differences were observed between patients undergoing ERA test and those not undergoing ERA test prior to ET in terms of live birth (OR 1.00, 95% CI 0.63-1.58, I2 = 92.7%), clinical pregnancy (OR 1.20, 95% CI 0.90-1.61, I2 = 86.5%), biochemical pregnancy (OR 0.83, 95% CI 0.46-1.49, I2 = 87%), positive pregnancy test (OR 0.99, 95% CI 0.80-1.22, I2 = 0%), miscarriage (OR 0.91, 95% CI 0.62-1.34, I2 = 67.1%), and implantation rate (OR 1.18, 95% CI 0.44-3.14, I2 = 93.2%). pET with ERA is not associated with any significant differences in pregnancy outcomes as compared to standard ET protocols. Therefore, the utility of ERA in patients undergoing IVF should be revisited.

Zoli, M., et al. (2021). "Management of sellar and parasellar tumors becoming symptomatic during pregnancy: a practical algorithm based on multi-center experience and systematic literature review." Pituitary 24(2): 269-283.
	INTRODUCTION: Sellar/parasellar tumors (SPTs) very rarely become symptomatic during pregnancy. No specific guidelines exist for their management, that is extremely challenging as mother and fetus health can be jeopardized. MATERIALS AND METHODS: Data of patients with SPTs becoming symptomatic during pregnancy treated at two Italian referral Centers were retrospectively collected. Systematic literature review was also performed. RESULTS: Our series consisted of 6 cases, 3 meningiomas, 1 ACTH-secreting adenoma, 1 pituicytoma and 1 craniopharyngioma. Mean age at presentation was 33.6 ± 6.0 years. Five patients complained of visual disturbances, associated with headache in one case, that occurred between gestation week (GW) 22 and 34. In 5 cases, pregnancy was uneventful with the delivery of a healthy baby between GW 33 and 35, followed by endoscopic surgical tumor exeresis (n = 4) or proton bean therapy (n = 1). Another patient presented with stigmata typical of Cushing's syndrome and rapidly worsening pre-eclampsia, that required pregnancy interruption and adenomectomy. Based on personal and literature cases, a practical algorithm was proposed to help clinicians dealing with these patients. CONCLUSIONS: SPTs becoming symptomatic in pregnancy deserve careful monitoring and multidisciplinary management. Overall, wait-and-see approach is suggested, reserving surgery to patients with rapidly progressive/life-threatening situations, significant risk of permanent neurological impairment or malignant lesions.

Zoloeva, I. A., et al. (2022). "[Efficiency of staged rehabilitation treatment of patients with chronic endometritis and reproductive disorders]." Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury 99(6. Vyp. 2): 36-43.
	The use of physical factors according to the principles of syndromic-pathogenic approach with the patients suffering from chronic endometritis ensures the restoration of physical and mental health.; Objective: To evaluate and scientifically substantiate therapeutic effects of staged rehabilitation treatment of the patients with chronic endometritis and reproductive disorders including therapeutic physical factors.; Material and Methods: There have been observed 103 patients of childbearing age with chronic endometritis and reproductive disorders. They were divided into two groups by simple randomization. In the control group ( n =49), the treatment was based on clinical guidelines and included antibacterial pharmacotherapy and magnetic laser therapy in combination with intravaginal magnetic laser electrical stimulation. In the main group ( n =54), this treatment was carried out at the I and II stages, however, at the II stage, a pulsed low-frequency electrostatic field was additionally included in the treatment program; clay therapy was included at the III stage. Clinical monitoring, cytokine status, and regional circulation were used to assess the effectiveness of the treatment.; Results: After a staged rehabilitation treatment, the reduction of clinical manifestations was observed in the main group in 89.2% ( p <0.01) of cases, while in the control group - in only 76.5% ( p <0.01). The patients of the main group had a decrease in the level of pro-inflammatory cytokines on average by 44.0% ( p <0.01), whereas the level of anti-inflammatory cytokines increased on average by 29.6% ( p <0.01). In the control group the dynamics of cytokine activity indicators was lower by 18-20% ( p <0.05). The use of physical factors provided a significant improvement in regional hemodynamics, and in all the cases there was a significant significance in relation to similar indicators in the control group. The effectiveness of personalized programs of rehabilitation treatment of the patients suffering from chronic endometritis and reproductive disorders was 78.4%, and standardized programs - 59.5%.; Conclusion: Staged rehabilitation treatment of chronic endometritis and infertility with the use of physical factors at each stage ensures the leveling of pain and inflammatory syndromes, improvement of immune status, pelvic hemodynamics, which, in general, provides an increase in the effectiveness of rehabilitation treatment of this category of patients by 18.9% ( p <0.05).

Zolton Jessica, R. (2023). "Polycystic ovarian syndrome: a second-take on flutamide." Fertility and Sterility 119(1): 127.
	
Zong, X., et al. (2023). "Obstetric and perinatal outcomes following frozen and fresh embryo transfer in patients with endometrial hyperplasia and carcinoma: a retrospective study in a high-volume reproductive center." BMC Pregnancy and Childbirth 23(1): 92.
	Background: There is ongoing debate regarding which embryo transfer procedure can achieve a higher live birth rate. Research has suggested that frozen ET might be beneficial for certain populations, such as hyper-responders. This study aimed to compare outcomes of pregnancies between frozen and fresh embryo transfer cycles in patients with endometrial hyperplasia and carcinoma.; Methods: This retrospective cohort study was conducted at a high-volume reproductive center from January 2010 to January 2022. Patients who were diagnosed with endometrial hyperplasia with atypia and endometrial carcinoma were included. They all underwent in vitro fertilization after conservative treatment. The primary outcome was live birth after frozen and fresh embryo transfer cycles, and secondary outcomes included perinatal complications and other pregnancy outcomes.; Results: Overall, 259 ET cycles (130 fresh and 129 frozen) were included. The rate of live births per embryo transfer cycle of the whole cohort was 20.8% (54/259), and no significant between-group difference was found after adjusting for potential confounding factors (23.8% vs. 17.8%; adjusted OR, 0.47; 95% CI, 0.21-1.06; p=0.068). Compared to fresh embryo transfer group, the incidence of total maternal complications in the frozen embryo transfer group was significantly higher (30.4% vs. 6.5%, p=0.019). Analyzing each complication as a separate entity, patients in the frozen embryo transfer group had a higher incidence of hypertensive disorders of pregnancy (p=0.028). Multiple logistic regression analysis showed that frozen embryo transfer was related with an increased occurrence of maternal complications (OR, 6.68, 95% CI, 1.01-44.19, p=0.040).; Conclusions: Among patients with endometrial hyperplasia and carcinoma, the rate of live births was comparable between both embryo transfer procedures, while frozen embryo transfer might be associated with a higher risk of maternal complications compared to that with fresh embryo transfer. (© 2023. The Author(s).)

Zoorob, D., et al. (2023). "Addition of Transversus Abdominis Plane Block to Conventional Pain Regimens in Robotic Sacrocolpopexy Procedures A Pilot Randomized Controlled Trial (SACROTAP)." Urogynecology 29(2): 139-143.
	Importance: There have been no randomized trials assessing the benefits of integration of transversus abdominis plane (TAP) blocks in sacrocolpopexy procedure postoperative pain management. Objective(s): The aim of this study was to assess the variation in pain perception upon adding TAP blocks to conventional oral pain medications in patients undergoing sacrocolpopexy. The primary outcome was the reduction in pain reported using the numeric rating scale (NRS) among patient groups. The secondary outcome was the change in narcotic analgesic use postoperatively. Study Design: This was a prospective double-blind, pilot randomized controlled trial of women undergoing robotic sacrocolpopexy, with and without supracervical hysterectomy, with 20 patients enrolled in each arm. Randomization included receiving a TAP block in addition to the conventional analgesic regimen. Result(s): A total of 48 women were approached to participate in the study; 40 women provided consent (20 per study arm) and completed the 7-day follow-up. Patients receiving a TAP block had lower NRS pain scores at 4 hours postoperatively (4.95 +/- 0.76 vs 5.50 +/- 0.61, P = 0.02), 7 days postoperatively (2.20 +/- 1.11 vs 3.15 +/- 1.04, P = 0.008), and lower cumulative NRS pain scores at 48 hours postoperatively (14.90 +/- 2.2 vs 16.60 +/- 2.04, P = 0.02) and 7 days postoperatively (17.10 +/- 2.63 vs 19.75 +/- 2.65, P = 0.003) than patients not receiving a block. Patients in the intervention group also had lower cumulative morphine milliequivalents at 7 days postoperatively (17.25 +/- 10.7 vs 29.25 +/- 14.53, P = 0.005). Conclusion(s): Use of TAP blocks in robotic sacrocolpopexy cases, with or without concurrent hysterectomy, may reduce postoperative pain and narcotic medication needs.Copyright © 2023 by the Author(s).

Zou, D., et al. (2022). "185MO Preliminary results of niraparib combined with brivanib or toripalimab dual therapy evaluation in recurrent, metastatic and persistent cervical cancer (CQGOG0101): An open-label, two cohorts, phase II clinical trial." Annals of Oncology 33(Supplement 9): S1508.
	Background: The aim of this study (CQGOG 0101, NCT04395612) is to evaluate the safety and activity of Niraparib (an oral PARP1/2 inhibitor) combined with brivanib (an anti-angiogenesis inhibitor) or Toripalimab (a PD-1 inhibitor) in patients with recurrent, metastatic, or persistent cervical cancer. Method(s): 30 patients were planned to be enrolled.Eligible patients were aged 18-70 years with measurable lesions and had an ECOG performance status of 0-2. Two cohorts were included in the study: Cohort 1:Subjects received oral Niraparib 200 mg and Brivanib 400 mg once daily. Cohort 2:Subjects received oral Niraparib 200 mg once daily and Intravenous Toripalimab 240 mg every 21 days. Treatment until until disease progression, intolerable toxicity, or withdrawal of consent. Primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR) and safety. Result(s): Between May 8th, 2020 and June 22nd, 2022, 23 patients (median age, 50 years old [28-73]) were enrolled. Patients had received a median of two (1-3) previous lines of platinum-based therapy. All of 23 patients had distant metastatic lesions. In Cohort 1, 9 patients had underwent at least one post baseline tumor assessment (To deadline for submission), including 1 confirmed partial response, 4 with stable disease, 4 with progressive disease, the ORR is 11%.No drug-related grade 3 or worse treatment-emergent adverse events were detected. In Cohort 2,13 patients had underwent at least one post baseline tumor assessment (To deadline for submission),including 8 confirmed stable disease, 4 with progressive disease, 1 withdrawal of consent. The median duration of treatment has not met yet. Treatment of Cohort 2 is still ongoing (Median follow-up is 2 months). Grade 3 or worse TEAEs were detected in 3 subjects. Conclusion(s): The Cohort 1 (Niraparib combined with Brivanib) seems to show a similar efficacy compared to other recurrent cervical cancer late-line therapies. The treatment of the Cohort 2 (Niraparib combined with Toripalimab) is still ongoing and final data will be reported later. Clinical trial identification: NCT04395612. Editorial acknowledgement: The authors thank the patients and their families. Legal entity responsible for the study: The authors. Funding(s): Zai Lab. Disclosure: All authors have declared no conflicts of interest.Copyright © 2022

Zou, J. and L. Jian (2023). "Inhibition of Ceramide Kinase Is Effective against Cisplatin-Resistant Ovarian Cancer Cells by Regulating Ceramide and C1P Levels." Gynecologic and Obstetric Investigation 88(1): 61-70.
	Objective: Chemoresistance in ovarian cancer results in treatment failure, yet underlying mechanisms that regulate chemoresistance remain largely unclear. There is emerging evidence relating ovarian cancer drug resistance with bioactive sphingolipids and regulation of sphingolipid metabolism. This work investigated the expression and function of ceramide kinase (CerK), a lipid kinase that regulates central bioactive sphingolipids, in ovarian cancer, as well as the therapeutic potential of targeting CERK.; Design: The levels of ceramide, ceramide 1-phosphate (C1P), and Cerk in ovarian cancer and normal counterparts were measured. Functions of Cerk in ovarian cancer were examined.; Materials, Setting, Methods: Immunohistochemistry, ELISA, and mass spectrometry methods were used to measure the level of ceramides, C1P, and CerK in primary tissues. Proliferation and apoptosis assays were performed in ovarian cancer cells after CERK depletion, CERK overexpression, and NVP-231 treatment in the absence or presence of cisplatin.; Results: Compared to normal ovarian cells, CerK and its mediating bioactive sphingolipids ceramide and C1P were decreased in ovarian cancer tissues. Interestingly, cisplatin-resistant ovarian cancer cells displayed increased CerK, decreased ceramide, and increased C1P, and furthermore, that CerK level was closely associated with ceramide and C1P levels in ovarian cancer cells. Functional analysis demonstrated that CerK overexpression was sufficient to promote growth and confer chemoresistance in ovarian cancer cells. CerK inhibition via both genetic and pharmacological approaches suppressed growth and induced apoptosis in cisplatin-resistant cells, and furthermore, this significantly augmented cisplatin's efficacy.; Limitations: The functional analysis of C1P was performed on in vitro ovarian cancer cells. In vivo studies were needed to further confirm the effects of CERK inhibition.; Conclusions: Our work is the first to show the critical role of CerK as the underlying mechanism of ovarian cancer chemoresistance, through regulating ceramide and C1P. (© 2023 S. Karger AG, Basel.)

Zou, M., et al. (2022). "Salinomycin-Loaded High-Density Lipoprotein Exerts Promising Anti-Ovarian Cancer Effects by Inhibiting Epithelial-Mesenchymal Transition." International journal of nanomedicine 17: 4059-4071.
	Background: Effective treatments for ovarian cancer remain elusive, and survival rates have long been considered grim. Ovarian cancer stem cells (OCSCs) and epithelial-mesenchymal transition (EMT) are associated with cancer progression and metastasis, as well as drug resistance and eventual treatment failure. Salinomycin (Sal) has an extensive effect on a variety of cancer stem cells (CSCs); however, its poor water solubility and toxicity to healthy tissues at high doses limit further research into its potential as an anti-cancer drug. We proposed a therapeutic strategy by constructing a tumor-targeting carrier that mimics high-density lipoprotein (HDL) to synthesize salinomycin-loaded high-density lipoprotein (S-HDL). This strategy helps reduce the side effects of salinomycin, thereby improving its clinical benefits.; Methods: OCSCs were isolated from ovarian cancer cells (OCCs) and the uptake of HDL nanoparticles was observed using laser confocal microscopes. After the cell viability analysis revealed the inhibitory effect of S-HDL on OCCs and OCSCs, the main biological processes influenced by S-HDL were predicted with a transcriptome sequencing analysis and verified in vitro and in vivo.; Results: Cellular uptake analysis showed that the HDL delivery system was able to significantly enhance the uptake of Sal by OCCs, tentatively validating the targeting role of recombinant HDL, so that S-HDL could reduce the toxicity of Sal and increase its anti-ovarian cancer effects. Conversely, S-HDL could exert anti-ovarian cancer effects by inhibiting the proliferation of OCCs and OCSCs, promoting apoptosis, blocking EMT, and suppressing stemness and angiogenesis-related protein expression in vitro and in vivo.; Conclusion: S-HDL had stronger anti-ovarian cancer effects than unencapsulated Sal. Thus, it may be a potential agent for ovarian cancer treatment in the future.; Competing Interests: The authors have declared that no competing interest exists. (© 2022 Zou et al.)

Zou, Y., et al. (2023). "Efficacy and safety of anti-angiogenesis agents combined with chemoradiotherapy in the treatment of locally advanced cervical cancer: a meta-analysis of randomized controlled trials." Expert Review of Anticancer Therapy 23(2): 217-227.
	Background: Neovascularization is an important factor causing radiotherapy resistance, tumor growth, and metastasis. It may provides a new direction for treatment of cervical cancer.; Objective and Methods: The main objective is to systematically evaluate the clinical efficacy and safety of antiangiogenic therapy combined with CCRT in the treatment of cervical cancer. We searched major Chinese and English databases to collect relevant studies from the database establishment up to April 2022. The experimental group of the studies included used CCRT combined with anti-angiogenic therapy, while another used only CCRT. We used the ' Cochrane Collaboration's tool' to assess risk of bias and RevMan 5.4 to conduct analysis.; Results: Twelve studies with 793 patients were included. Use clinical efficiency and adverse reactions as effect indicators. It showed that the combination can improve the ORR (OR = 3.52, P < 0.00001), CR(OR = 2.46, P < 0.00001), DCR (OR = 2.64, P = 0.005), and OS(HR = 0.56, P = 0.03). But it increases the risk of neutropenia (OR = 1.86, P = 0.004) and hypertension (OR = 5.57, P = 0.003).; Conclusions: Combined therapy can improve the clinical efficacy of cervical cancer, but the safety needs to be considered.

Zouridis, A. and H. Soleymani (2022). "IS LAPAROSCOPY A SAFE APPROACH FOR TREATMENT OF STAGE II ENDOMETRIAL CANCER? A SINGLE CENTRE 10 YEARS EXPERIENCE." International Journal of Gynecological Cancer 32(Supplement 2): A106-A107.
	Introduction/Background Although minimal invasive approach has been established as the standard surgical treatment in early stage endometrial cancer, the oncological safety of laparoscopy when cervix is involved is not based on strong evidence. Our retrospective analysis aims to investigate whether there is any difference on overall and cancer specific survival between patients treated by laparoscopy and laparotomy for stage II endometrial cancer in a single Cancer Centre over a decade. Methodology Our cohort consisted of all patients operated in Oxford University Hospitals Trust between 2010 and 2020 with microscopically proven stage II endometrial cancer. The audit was registered according to the local equirements with registration number 5832. Categorical variables were compared using chi-square test and continuous variables with independent samples t-test. Survival rates were determined from Kaplan-Meier Curves and compared using log-rank test. Statistical significance was considered for p<0.05. Results Of the 47 patient of our cohort 33 (70%) underwent laparoscopy, whereas 14 patients were treated with laparotomy (30%). There was no difference in mean age (p=0.86), mean BMI (p=0.76) and comorbidity index (p=0.96) between the two groups. Histopathological features were also similar in terms of histological type (p=0.32), LVSI (p=0.15) and depth of myometrial invasion (p=0.07). Patients in both groups recieved similar adjuvant treatment (p=0.11). There was no difference on overall (p=0.606) and cancer specific survival (p=0.564) between the two groups. The estimated overall 5-year survival was 65.5% for the laparoscopy and 50% for the laparotomy group and the disease specific 5-year survival 79.3% and 67.7% respectively. Conclusion In our study we did not find any difference in overall and cancer specific survival between the two approaches. To clearly identify any potential adverse outcomes in relapse or survival terms regarding minimal invasive compared to open surgery in stage II endometrial cancer a prospective randomized trial is required.

Zuber, S. G., et al. (2022). "GSOR16 Presentation Time: 11:45 AM: Financial Toxicity in Patients Undergoing Brachytherapy for Gynecologic Cancers." Brachytherapy 21(6 Supplement): S60-S61.
	Purpose: Financial toxicity (FT) affects about 50% of patients with gynecologic cancer. Brachytherapy (BT) is an important component of treatment for many of these patients. We aimed to assess factors that contribute to FT in patients with gynecologic cancer who undergo BT. Material(s) and Method(s): Gynecologic oncology patients undergoing BT from October 2017-February 2021 completed a survey that included demographics, the EQ-5D-3L to measure quality of life, and Comprehensive Score for Financial Toxicity (COST) tool to measure economic burden. High FT was defined as a COST score <=23. We stratified patients into 3 groups: vaginal BT (VBT) only, VBT with external beam radiation therapy (EBRT + VBT), or "other" types of BT with external beam radiation therapy (EBRT + other BT). "Other" types of BT included tandem and ovoids, tandem and ring, and interstitial implants. Data presented as percent or median (interquartile range) and compared with Chi-square/Fisher's exact test and Wilcoxon rank-sum test, respectively. We used modified Poisson regression to calculate risk ratios (RR) and 95% confidence intervals (CI) with high FT as the outcome and type of BT as the exposure. Result(s): Among 101 respondents, median COST score was 30 (IQR 21-35); 28% had high FT [median COST: 14 (IQR 9-19)] and 72% had low FT [median COST: 32 (IQR 28-37)]. Respondents were white (81%), 9% Black, and 7% Asian. Median age was 63 (57-71), with a younger age in the high FT group [59 (49-62)] compared to the low FT group [67 (61-72), p<0.01]. Patients in the high FT group were more likely to be single (32%) compared to those in the low FT group (10%, p=0.01). In the high FT group, 68% of patients had private insurance, whereas 38% had private insurance in the low FT group (p<0.01). Most patients (71%) had uterine cancer, followed by cervical (23%) and vaginal/vulvar (6%) cancer. The majority (69%) of the entire group had stage I disease, with more patients in the low FT cohort having stage I disease (75%) compared to the high FT cohort (54%, p=0.03). Within the treatment groups, 51% received VBT alone, 29% received EBRT + VBT, and 21% received EBRT + other BT. The type of BT was significantly associated with FT. VBT alone was more common in the low FT group (58%) than the high FT group (32%), and EBRT + VBT was less common in the low FT group (21%) than the high FT group (50%, p=0.01). Patients who had EBRT + VBT were 2.8 times (95%, CI 1.2-6.5) more likely to have high FT compared to VBT patients; this association was attenuated when adjusting for age and insurance (RR 2.0; 95%, CI 0.84-4.7). Of the assessed cost-coping strategies, borrowing money was reported by 31% of the EBRT + VBT, 24% of the EBRT + other BT, and 2% of the VBT groups (p<0.01), and reduced leisure spending was reported by 31% of the EBRT + VBT, 5% of the EBRT + other BT, and 16% of the VBT groups (p<0.01). Conclusion(s): A substantial proportion of patients going through BT have high FT. Younger age, being single, having private insurance, and higher stage disease were associated with higher FT. There is a higher risk of FT associated with undergoing EBRT. Patients who go through only VBT were least likely to have high FT. Patients going through EBRT were more likely to borrow money and reduce leisure spending as cost-coping strategies. Further research is needed to understand specific drivers of high FT for patients receiving EBRT and BT and to evaluate FT over time.Copyright © 2022

Zuber, S. G., et al. (2022). "Financial Toxicity in Patients with Gynecologic Cancer Undergoing Brachytherapy." International journal of radiation oncology biology physics 114(3 Supplement): e455-e456.
	Purpose/Objective(s): Financial toxicity (FT) affects about 50% of patients with gynecologic cancer. Brachytherapy (BT) is an important component of treatment for many of these patients. We aimed to assess factors that contribute to FT in patients with gynecologic cancer who undergo BT. Materials/Methods: Gynecologic oncology patients undergoing BT from October 2017-February 2021 completed a survey that included demographics, EQ-5D-3L to measure quality of life, and Comprehensive Score for Financial Toxicity (COST) tool to measure FT. High FT was defined as a COST score <=23. We stratified patients into 3 groups: vaginal BT (VBT) only, VBT with external beam radiation therapy (EBRT + VBT), or "other" types of BT with external beam radiation therapy (EBRT + other BT). "Other" types of BT included tandem with ovoids/ring and interstitials. Data are presented as percent or median (interquartile range) and compared with Chi-square/Fisher's exact test and Wilcoxon rank-sum test, respectively. We used modified Poisson regression to calculate risk ratios (RR) and 95% confidence intervals (CI). Result(s): Among 101 respondents, median COST score was 30 (21-35); 28% had high FT (median COST: 14 (9-19)) and 72% had low FT (median COST: 32 (28-37)). Respondents were white (81%), 9% Black, and 7% Asian. Median age was 63 (57-71), with a younger age in the high FT group [59 (49-62)] compared to the low FT group [67 (61-72), p<0.01]. In the high FT group, 68% of patients had private insurance, whereas 38% had private insurance in the low FT group (p<0.01). Most patients (71%) had uterine cancer, followed by cervical (23%) and vaginal/vulvar (6%) cancer. The majority (69%) had stage I disease; 51% received VBT alone, 29% received EBRT + VBT, and 21% received EBRT + other BT. Treatment group was significantly associated with FT. VBT alone was more common in the low FT group (58%) than the high FT group (32%), and EBRT + VBT was less common in the low FT group (21%) than the high FT group (50%, p=0.01). Patients who had EBRT + VBT were 2.8 times (95% CI 1.2-6.5) more likely to have high FT compared to VBT patients; this association was attenuated when adjusting for age and insurance (RR 2.0; 95% CI 0.84-4.7). Of the assessed cost-coping strategies, borrowing money was reported by 31% of the EBRT + VBT, 24% of the EBRT + other BT, and 2% of the VBT groups (p<0.01), and reduced leisure spending was reported by 31% of the EBRT + VBT, 5% of the EBRT + other BT, and 16% of the VBT groups (p<0.01). Conclusion(s): A substantial proportion of patients going through BT have high FT. Younger age and private insurance were associated with higher FT. There is a higher risk of FT associated with undergoing EBRT. Patients who go through only VBT were least likely to have high FT. Patients going through EBRT were more likely to borrow money and reduce leisure spending as cost-coping strategies. Further research is needed to understand specific drivers of high FT for patients receiving EBRT and to evaluate FT over time.Copyright © 2022

Zuo, Q.-Q., et al. (2022). "Clinical efficacy of Wenjing decoction in the treatment of ovulatory disorder infertility: A systematic review and meta-analysis." Medicine 101(28): e29640.
	Objectives: Wenjing decoction (WJD) was widely used in the treatment for ovulatory disorder infertility (ODI) in China, while its efficacy was not clearly known. In this study, we evaluated the clinical efficacy of WJD by meta-analysis.; Methods: Eight electronic databases including Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP Database, and China Biology Medicine were searched for randomized controlled trials (RCTs) published from the inception of each database to July 1, 2021, of which the interventions involve WJD and clomiphene. Outcomes included clinical efficacy rate, pregnancy rate, ovulation rate, dominant follicle diameter, endometrial thickness, estradiol, follicle-stimulating hormone, and luteinizing hormone. Meta-analysis and risk of bias were performed by RevMan 5.3 software.; Results: Eleven RCTs including 915 patients, of which 476 in the intervention group and 439 in the control group. Meta-analysis showed that WJD was better than clomiphene for patients with ODI in terms of clinical effective rate (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.08-1.34), pregnancy rate (OR = 1.54, 95% CI: 1.15-2.07), ovulation rate (OR = 1.34, 95% CI: 1.07-1.67), endometrial thickness (mean difference [MD] = 1.50, 95% CI: 0.90-2.10), and dominant follicle diameter (MD = 1.85, 95% CI: 0.68-3.02). The estradiol level (MD = 91.0, 95% CI: 80.3-101.88) in patients taking WJD was significantly higher than those taking clomiphene, while the follicle-stimulating hormone level (MD = -0.93, 95% CI: -1.13 to -0.72) and the luteinizing hormone level (MD = -4.41, 95% CI: -4.80 to -4.03) in patients taking WJD was significantly lower than those taking clomiphene. Our results also indicated that WJD combined with clomiphene was better than clomiphene alone for patients with ODI in terms of pregnancy rate (OR = 1.79, 95% CI: 1.37-2.35).; Conclusions: WJD may be effective in the treatment of patients with ODI. Due to the quality and quantity of literature, RCT with large sample size and high quality need to be performed to verify our conclusion.; Competing Interests: The authors have no conflicts of interest to disclose. (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zuo, S., et al. (2022). "Frailty and Acute Postoperative Urinary Retention in Older Women Undergoing Pelvic Organ Prolapse Surgery." International Urogynecology Journal 33(Supplement 2): S191-S192.
	Introduction: Acute postoperative urinary retention (POUR) is common following pelvic organ prolapse surgery, occurring in 15-45% of women. Some studies have reported that older age is associated with POUR. Although frailty is known to be associated with adverse postoperative outcomes, there is a paucity of data on the relationship between frailty and POUR. Objective(s): We aimed to examine the association between frailty, as defined by the Fried Frailty Index (FFI), and POUR in older women who underwent pelvic organ prolapse surgery. Method(s): This was a secondary analysis of a prospective study on postoperative delirium which enrolled women >=60 years old undergoing prolapse surgery at a large academic center from October 2016 to December 2019. Exclusion criteria included history of cognitive impairment and major neurologic disorder. The FFI, measured for each patient prior to surgery, includes the following components: self-reported unintentional weight loss >=10 pounds over the past year, self-reported exhaustion, low activity with calculated expenditure of less than 270 calories/week, decreased hand grip strength, and slowed walking speed. Total FFI score of 3 or above is categorized a "frail," score of 1-2 is "prefrail," and score of 0 is "not frail." The primary outcome is acute POUR, defined as requiring bladder catheterization at hospital discharge due to urinary retention. Chi-square (or Fisher's exact) for categorical variables and Student's t-test for continuous variables were used to compare characteristics across patients with or without POUR. Univariable logistic regression was performed to assess for risk factors of POUR in this cohort. An exploratory multivariable logistic regression was performed with forward additions and confirmed with backward removal techniques using relevant (age) and candidate variables with p<0.2 on univariable regression (body mass index (BMI), surgical approach, concomitant incontinence procedure, decreased grip strength). Result(s): Analyses were conducted on the full dataset of 165 women with mean age of 72.5+/-6.1 years and BMI of 28.0+/-4.4 kg/m2 (Table 1). Most women were White (n=153, 93.3%). There were 50 laparoscopic/robotic apical suspension procedures (30.3%), 44 colpocleisis/ colpectomies (26.7%), and 44 vaginal colpopexy procedures (26.7%). Nine (5.5%) women underwent a concomitant incontinence procedure. Most patients were discharged on the day of surgery (n=139, 84.2%), and 25/26 admitted patients were discharged the following day. At time of discharge, 47.3% (n=78) had acute POUR. Thirty-one women (18.8%) met criteria for "not frail," 115 (88.5%) were "pre-frail," and 19 (11.5%) were "frail." Frailty, by classification and by FFI score, was not associated with POUR. In an analysis of individual FFI components, self-reported unintentional weight loss was significantly associated with POUR (OR 4.6, 95% CI [1.23-17.15]). Of 14 women reporting unintentional weight loss, 7 (50%) met criteria for frailty, and 11 (78.6%) had acute POUR. There remained a significant association between unintentional weight loss and POUR on multivariable logistic regression (aOR 4.04, 95% CI [1.0-16.38], Table 2). Conclusion(s): In this cohort of older women who underwent surgical prolapse repair, frailty was not associated with POUR. Further prospective studies are needed to explore the observed risk of POUR in older women reporting unintended weight loss in the year preceding surgery.

Zuo Stephanie, W., et al. (2023). "Frailty and Acute Postoperative Urinary Retention in Older Women Undergoing Pelvic Organ Prolapse Surgery." Urogynecology (Philadelphia, Pa.) 29(2): 168-174.
	Importance: Acute postoperative urinary retention (POUR) is common after pelvic reconstructive surgery, occurring in 15-45% of women. There is a paucity of data on the relationship between frailty and POUR after prolapse surgery.; Objective: This study aimed to examine the association between frailty and POUR in older women who underwent pelvic organ prolapse surgery.; Study Design: This secondary analysis of a prospective study of postoperative delirium enrolled women 60 years and older undergoing prolapse surgery. The Fried Frailty Index was used to assess frailty before surgery. Acute POUR was defined as failure to pass a retrograde voiding trial at hospital discharge with postvoid residual volume of greater than 100 mL.; Results: Analyses included 165 women, with a mean ± SD age of 72.5 ± 6.1 years and a body mass index of 28.0 ± 4.4 kg/m2. There were 49 laparoscopic/robotic apical suspension procedures (29.7%), 60 vaginal obliterative procedures (36.4%), 47 vaginal apical suspension procedures (28.5%), and 9 isolated anterior and/or posterior colporrhaphies (5.5%), of which 9 had a concomitant incontinence procedure. Seventy-eight women (47.3%) experienced acute POUR. Thirty-one (18.8%) met the criteria for "not frail," 115 (88.5%) were "prefrail," and 19 (11.5%) were "frail." Neither frailty status nor score was associated with POUR. In an analysis of individual Fried Frailty Index components, self-reported unintentional weight loss was significantly associated with POUR (odds ratio, 4.6; 95% confidence interval, 1.23-17.15). This remained significant on multivariable logistic regression (adjusted odds ratio, 4.06; 95% confidence interval, 1.01-16.39).; Conclusions: Frailty was not associated with POUR in older women undergoing prolapse surgery. The observed association between POUR and unintended weight loss before surgery warrants further investigation.; Competing Interests: M.F.A. is supported by the National Institute on Aging (R03AG064378-01, K23AG073517-01) and the Pennsylvania Department of Health (4100088553). M.F.A.'s spouse is employed by Johnson & Johnson Corporate. The rest of the authors have declared no conflict of interest. (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Zwaans, B., et al. (2023). "BLADDER-DIRECTED VERSUS PELVIC FLOOR THERAPY IN WOMEN WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME: PRELIMINARY RESULTS." Journal of urology 209: e149.
	INTRODUCTION AND OBJECTIVE: Interstitial cystitis/bladder pain syndrome (IC/BPS) symptoms appear bladder related, though little solid evidence exists linking IC/BPS symptoms to dysfunctional bladder epithelium unless ulcers are present. Growing evidence suggests IC/ BPS may be a more diffuse syndrome. The study objective is to compare IC/BPS symptom improvement in pelvic floor versus bladder directed therapies. METHODS: Women 18 to 85 years with history of IC/BPS were randomized to one of two treatment arms: 1. Pelvic Floor Physical Therapy (PFPT), 2. Bladder directed instillation of lidocaine, heparin sulphate, sodium bicarbonate, and Kenalog. All participants received twice weekly treatments for 8 consecutive weeks. Symptom improvement was assessed using 3‐day voiding diary, pain assessment, and validated questionnaires: global response assessment (GRA), Interstitial cystitis symptom index (ICSI) and Interstitial cystitis problem index (ICPI), at baseline, treatment mid‐ and end‐points (V8 and V17), and 6 months follow‐up (V18). Statistical analysis was performed using ANOVA followed by Dunnett's multiple comparison. RESULTS: 31 women were enrolled and randomized to PFPT (n=15) or Instillation (n=16) arm with average age of 46.8 and 48.7 respectively. By end of treatment 67% in PFPT versus 54% in instillation group reported significant improvement of symptoms (GRA). Urinary frequency was significantly reduced in PFPT group at all time points (Figure 1) and was resolved or improved in 75% of patients in PFPT compared to 33% in instillation group. Both treatments significantly improved Maximum pelvic pain, but reduction in pain was no longer significant in PFPT group by V18 (Figure 1). Pain Catastrophizing Scale scores followed the same trend. Urgency did not improve with either treatment. ICSI and ICPI scores were significantly reduced by V8 and remained constant up to V18. No severe adverse events were reported. Four patients developed urinary tract infections during treatment, 1 in PFPT and 3 in instillation group. CONCLUSIONS: Both treatments significantly improved IC/ BPS symptoms, with patients in PFPT reporting higher GRA scores and frequency improvement. In contrast, instillation appeared superior in reducing maximum pelvic pain long‐term.

Zwolsman, S., et al. (2019). "Heterogeneity of cost estimates in health economic evaluation research. A systematic review of stress urinary incontinence studies." International Urogynecology Journal 30(7): 1045-1059.
	INTRODUCTION AND HYPOTHESIS: There is increased demand for an international overview of cost estimates and insight into the variation affecting these estimates. Understanding of these costs is useful for cost-effectiveness analysis (CEA) research into new treatment modalities and for clinical guideline development. METHODS: A systematic search was conducted in Ovid MEDLINE & other non-indexed materials and Ovid Embase for articles published between 1995 and 2017. The National Health Service Economic Evaluation Database (NHS-EED) filter and the McMaster sensitive therapy filter were combined with a bespoke search strategy for stress urinary incontinence (SUI). We extracted unit cost estimates, assessed variability and methodology, and determined transferability. RESULTS: We included 37 studies in this review. Four hundred and eighty-two cost estimates from 13 countries worldwide were extracted. Descriptive analysis shows that hospital stay in gynecology ranged between €82 and €1,292 per day. Costs of gynecological consultation range from €30 in France to €158 in Sweden. In the UK, costs are estimated at €228 per hour. Costs of a tension-free vaginal tape (TVT) device range from €431 in Finland to €994 in Canada. TVT surgery per minute costs €25 in France and €82 in Sweden. Total costs of TVT range from €1,224 in Ireland to €5,809 for inpatient care in France. Variation was explored. CONCLUSIONS: Heterogeneity was observed in cost estimates for all units at all levels of health care. CEAs of SUI interventions cannot be interpreted without bias when the base of these analyses-namely costs-cannot be compared and generalized.

الهام, ن., et al. (2022). "ارزیابی اثربخشی و عوارض جانبی کاتتر ویژه تلقیح داخل رحمی اسپرم در زوج‌های نازا، یک کارآزمایی بالینی تصادفی." Journal of shaheed sadoughi university of medical sciences & health services 30(3): 4682‐4691.
	
محبوبه, ف., et al. (2022). "تأثیر 6 هفته تمرینات پایداری عصبی- عضالنی پویا بر کنترل ادرار و کیفیت زندگی زنان سالمند." Journal of safety promotion & injury prevention 10(1): 33‐42.
	Background and Objectives: Urinary incontinence is one of the most common problems in aging that negatively affects the quality of life. This study aimed to investigate the effect of “Dynamic Neuromuscular Stabilization” (DNS) exercises on urine control and quality of life in elderly women with urinary incontinence. Methods and Materials: This study was a semi-experimental study with a pre-test-post-test design with the control group. The 24agedfemales, 60years and over with urinary incontinence, were selected as statistical samples based on inclusion criteria and were randomly divided into treatment group (N= 12) and control group (N= 12). Before and after 6 weeks of training which were performed for 45minutes and 6 sessions per week, the quality of life of the subjects was assessed by the IncontinenceQualityof Life Questionnaire (I-QOL) and the severity of urinary incontinence was assessed by International Consultation on IncontinenceQuestionnaire-Short Form (ICIQ-SF) using repeated measures analysis of variance. Results: The results showed that urinary incontinence and quality of life in the treatment group significantly improved in the post-test compared to the pre-test (P <0.05). Also, there was a significant difference in all variables between the treatment and control groups in the post-test (P <0.05).Conclusion: According to the results, by doing exercises for 6 weeks, urinary incontinence and subsequently the quality of life of elderly women with urinary incontinence will improve. Therefore, these exercises are recommended to elderly women as a safe and secure intervention.

장순양 (2021). "부인암 여성을 위한 성건강 향상 프로그램 개발과 효과." Asian oncology nursing 21(3): 163‐172.
	
李声, et al. (2019). "Meta Analysis of Needling and Western Medicine for Perimenopausal Depression Symptoms." 中国老年学杂志 39(8): 1891-1896.
	Objective To compare the clinical efficacy of needling and Western medicine in the treatment of perimenopausal depression by using evidence-based medical methods. Method of retrieving clinical research literature on acerbic treatment of perimenopausal depression in PubMed, Cochrane, Embase, Web of Science, Chinese Journal Database, Chinese Biomedical Biomedical Library .by 2 majors Literary readers used ENDNOTE X8 to manage the literature based on the inclusion of standard screening literature, evaluated the quality of the literature using the Cochrane Evaluation Manual, and used Reman5.3 for statistical analysis. The results were included in 31 randomized controlled trials with a total of 2638 patients.Meta analysis results showed: in total efficiency [OR=2.29,95,% CI ( 1.83 to 2.87), P<0.00001] and MENQOL (standardized average standard deviation (SMD) = -0.45,95% CI (-0.72~-0.17), P=0.001] were statistically significant, acupuncture group efficacy was significantly better than the western medicine group. 1.34~ 0.17), P=0.13], serum estradiol (E2) [SMD=-0.07,95% CI (-1.30~1.15), P=0.91), follicular genesis hormone (FSL) (SMD=-0.41,95% CI (-1.05~0.22), P=0.20), luteopoietin (LH) (SMD=0.06,95% CI (-0.17 to 0.28), P=0.61] The difference is not statistically significant, the acupuncture group is comparable to the Western drug group. Conclusion acupuncture improves menopausal depressive symptoms, quality of menopausal life clinical efficacy is better than western medicine, improves menopausal syndrome symptoms, regulatory hormone levels are comparable with western medicine.

邓, 菁. and 佩. 李 (2023). "Efficacy of different antioxidants in patients with polycystic ovaries."
	
郭葵 and 陈曙 (2020). "Systematic Evaluation of Effectiveness and Safety in the Treatment of Primary Dysenorrhea." 湖南中医杂志 36(5): 126-130.
	Objective: Systematic evaluation of the effectiveness and safety of the treatment of primary dysmenorrhea (PD). Method: Comprehensive retrieval of the Chinese Biomedical Literature Database (CBM), CNKI, VIP Chinese Science and Technology Journal Database (VIP), Wanfang Data (WANFANG DATA), PubMed, Cochrane and others Zhongguan Clinical Research on Therapeutics of PD literature, selection of eligible literature for meta analysis. Results: Total 1,100 patients with PD were incorporated in 14 literature. Meta analysis showed total efficiency [RR=1.36,95% CI (1.24,1.49), Z=6.70, P^0.00001]; cure rate [RR=1.76,95% CI ( 1.35,2.28), Z=4.22, P^0.0001]; Visual Simulation Pain Scale Score [MD=-14.59,95% CI (-28.67, -0.51), Z=2.03, P=0.04]; Prostaglandin levels [MD=-2.77,95% CI (-14.57,9.03), Z=0.46, P= 0.65]; uterine hemodynamics, resistance index [MD=-0.15,95% CI (-0.20, -0.10), Z=5.97, P^0.00001], pacing index [MD=-0.69,95% CI (-0.74, -0.64), Z=25.79, P^0.00001], contraction period peak/diastolic period [ MD=-2.27,95% CI (-2.40, -2.14), Z=33.41, P≈ 0.00001], and the difference between the two groups was not statistically significant in the tolla group (including Western medicine, Chinese medicine, acupuncture). Conclusion: PD efficacy of tolla treatment is accurate and safe.

钱嘉璐 and 余晓燕 (2020). "悲伤支持对围生期丧失家庭焦虑、抑郁、 悲伤症状影响的系统评价." Chinese Nursing Research 34(17): 3017-3025.
	Objective：To systematically evaluate the effect of bereavement support on anxiety，depression and grief symptoms in families experienced perinatal loss. Methods：The randomized controlled trials related to the effects of bereavement support on anxiety， depression and grief in families with perinatal loss were searched in PubMed，EMbase，Cochrane，Web of Science，CNKI，Wanfang，VIP， CBM. The search period was from the database establishment to 11th August 2019. Two researchers independently screened the literatures，exacted data and assessed the quality of included literatures. RevMan 5. 3 software was used in data analysis. Results：A total of seven RCTs were recruited. It included 1 384 participants，678 in the intervention group and 706 in the control group. The results showed that，compared with conventional nursing，bereavement support was effective in reducing anxiety［SMD=-0. 39，95%CI （-0. 68，-0. 11），Z=2. 70，P=0. 007］and depression［SMD=-0. 40，95%CI（-0. 67，0. 14），Z=2. 99，P=0. 003）］. Conclusion： Current evidences showed that bereavement support could effectively reduce the level of anxiety and depression in perinatal loss families. Bereavement support provided for families with perinatal loss experience，should be implemented from the perspective of changing their internal cognition and enhancing external support.

陈梅, et al. (2019). "Meta analysis of the clinical study of thermosensitive acupuncture treatment of primary menstrual." 中医药通报 18(1): 31-37.
	Objective: Systematic evaluation of the clinical efficacy and safety of thermosensitive acupuncture in treatment of primary dysmenorrhea. Methods: Computer Retrieval of China Internet Database (CNKI), Wanfang Database (WANFANG), Chongqing VIP Database (VIP), Chinese Biomedical Documentation Database (CBM), American Medicine Online (PubMed) and International Certified Medical Library Cochrane library (Issue1,2018), retrieving a randomized controlled trial (RCT) on thermosensitive acupuncture treatment of primary dysmenorrhea published in March 2018. 881 patients , Meta analysis showed that the total efficacy and healing rate were higher in the treatment group than in the control group. The difference between the thermist-acupuncture group and the western drug group was statistically significant [OR=4.68,95% CI (2.27,9.65); OR=3.10,95% CI (2.01,4.79)]. The therapy group compares its total effectiveness and cure rate Differences are statistically significant [OR=4.97,95% CI (2.96,8.36); OR=2.94,95% CI (1.72,5.02)]. Conclusion: Thermal acupuncture treatment is better than Western medicine and other acupuncture therapies such as traditional and warm acupuncture.